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pmc-6188725-1
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An 85-year-old woman presented to our emergency room (ER) with severe epigastric pain for one day. Pain was associated with nausea and coffee ground vomiting with feculent odor. Prior to this admission she had nonspecific abdominal discomfort with dark stools for one week and objective weight loss of 37 pounds since her last visit to the ER three years earlier. Her medical history included hypertension, diabetes mellitus, and osteoporosis. In the ER, her vitals were within normal limits, and physical examination was unremarkable except for mild abdominal tenderness and palpable prominence in the left upper quadrant. Her laboratory investigations revealed hemoglobin of 9.3g/dl, mean corpuscular volume of 76fl, white blood cell count of 9.5 k/ul, platelet count of 529 k/ul, BUN of 63 mg/dl, and creatinine of 2.1 mg/dl.
Computed tomography (CT) scan of the abdomen without contrast done in the emergency room showed gastric wall thickening with possible gastric mass. She was admitted to the medical service and had an upper endoscopy showing a large cratered gastric ulcer in the greater curvature of the body with excessive amount of feculent material (see ) which raised suspicion for possible fistulous connection to the large bowel. Repeat abdominal CT scan with oral and intravenous contrast confirmed suspicion of distal transverse colon mass with gastrocolic fistula (see ). Subsequent colonoscopy revealed a large, circumferential, obstructing transverse colon mass (see ). Pathology showed poorly differentiated adenocarcinoma of the colon and on immunohistochemical stain, the tumor cells were positive for CK20 and CDX2 and weakly positive for CK7, features which are consistent with colon primary. She was managed surgically with an en bloc resection of tumor with partial gastrectomy and end-to-end colonic anastomosis. Postsurgical course was uneventful and she was discharged home in stable condition. Adjuvant chemotherapy was started outpatient after risks and benefits were discussed.
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pmc-6188732-1
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A 51-year-old previously healthy and physically active woman presented as an outpatient with complaints of lightheadedness and dizziness. In addition to her activities of daily living, the patient plays competitive tennis without any limitations or symptoms. Recently, while doing aerial yoga, she felt lightheaded and experienced a presyncopal episode, specifically while hanging upside down and performing hand stands. On physical exam, vital signs were normal and the exam was unremarkable except for the cardiac exam. The precordium was quiet with no displacement of the point of maximal impulse. There was a grade III/VI systolic murmur at the left sternal border and the electrocardiogram revealed a left bundle branch block. Subsequently, a transthoracic echocardiogram was performed and revealed a mass in the right ventricle attached to the posterior wall and prolapsing into the right ventricular outflow tract (RVOT) in systole ().
Next, a transesophageal echocardiogram was performed to better characterize the mass, which measured 2.6 cm × 4.1 cm and was mobile and prolapsed into the RVOT during systole resulting in a mild dynamic obstruction (). Color Doppler revealed turbulent flow in the RVOT and pressure gradient measurements revealed a gradient of 26 mmHg across the RVOT while the patient was heavily sedated and in a supine position (). We suspect that with aerial yoga, and the resulting upside-down suspension, the gradient would be higher. Therefore, the obstruction would be enhanced, resulting in decreased cardiac output and cerebral hypoperfusion, which could explain the presenting symptoms of lightheadedness and dizziness. The patient was referred to cardiothoracic surgery for further evaluation and underwent a cardiac catheterization prior to thoracotomy which also showed evidence of a RV mass (). A thoracotomy with excision of the mass was performed (), and pathological examination revealed the mass as a myxoma (). The patient had an uneventful recovery and was discharged home. She has been continued to follow up regularly two years postresection of the myxoma and continues to do well. She continues to experience no limitations in performing her activities of daily living nor while playing competitive tennis or performing aerial yoga. Repeat echocardiogram two years postresection did not reveal any evidence of recurrence of the myxoma (Figures and ).
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pmc-6188733-1
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A 27-year-old male presented with a 1-day history of intermittent gross painless hematuria. His past medical history included herniated lumbosacral disk with radiculopathy, otherwise unremarkable. Social history included current smoking, 6 pack/year, and occasional EtOH. The patient was single and had no children; family history was negative for genitourinary malignancies. Physical examination was unremarkable with BMI 23 and BP 120/86 and no prescribed medicines or drug use. Laboratory tests showed normal CBC, normal coagulation profile, and normal renal function.
Axial, contrast-enhanced CT demonstrated a centrally located, 4 x 4 x 4.6 cm, lobulated mass invading the renal vein and extending into the lumen of the infrahepatic inferior vena cava (). CT angiography of the chest showed no evidence of detectable pulmonary emboli and bone scan was negative for metastases.
Right radical nephrectomy, partial adrenalectomy, inferior vena cava tumor thrombectomy (infrahepatic), and extended retroperitoneal lymphadenectomy were performed; flexible cystoscopy performed during this surgery showed a bulbar urethral stricture (not clinically significant) and otherwise normal bladder. The intravascular tumor pedicle was easily removed intact from the vein lumen by pulling.
Gross examination of the nephrectomy specimen demonstrated a centrally located tumor with no gross invasion of adjacent tissue but with the pedicle extending into the inferior vena cava (). Grossly, the tumor pedicle had a smooth surface and no attachment to the renal vein. Grossly, the mass was partially cystic with variably sized cysts with a smooth lining. The intervening stroma formed grossly discernible nodules of variable thickness. No tumor necrosis was grossly apparent. The lesion appeared to be well demarcated with no invasion of adjacent kidney parenchyma.
Microscopically, the tumor was well demarcated with an elongated pedicle bulging into the renal pelvis and renal vein and a biphasic morphology with spindle cell stroma and a benign epithelial monolayer lining the cystic spaces (). The stromal component was composed of uniform spindle cells without cellular atypia, necrosis, or mitoses (). Focally, the stroma was densely cellular, resembling ovarian stroma, but no areas of scarring or fibrosis resembling corpora albicantia of the ovary were identified (). No blastemal, skeletal muscle or clusters of clear cells were seen. The cystic spaces were lined by a single layer of epithelium, which was cuboidal or flattened or, focally, had a hobnail appearance ().
The stromal cells were diffusely and uniformly positive for SMA () and desmin and, focally, for CD10, while stains for inhibin, CD34, WT-1, S-100, MART1, and HMB-45 were negative. The epithelial component was positive for CK7 (), for PAX-8, and, focally, for CD10. Immunostains for ER and PR were negative in stromal and epithelial components. The ki-67 index was low (<2%).
The tumor pedicle extending into the inferior vena cava showed similar morphology except for some edema and a focal procedure-related hemorrhage. Specifically, no epithelioid morphology and no tumor necrosis or mitoses were seen despite extensive sampling. The pedicle appeared to be floating in the vascular lumen without attachment to, or invasion of, the vascular wall (). The outer surface of the tumor pedicle was covered by endothelial (CD31/CD34 positive) cells (not shown).
FISH studies for ETV6 rearrangement by an ETV6 break-apart probe on chromosome 12 at 12p13.2 and for SS18 by a synovial sarcoma break-apart probe on chromosome 18q11.2 were negative.
A diagnosis of “mixed epithelial and stromal tumor (MEST) of the kidney with extension into IVC” was rendered. After surgery, the patient recovered uneventfully and no recurrences have been reported at 3 years' follow-up.
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pmc-6188736-1
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The patient was a 60-year-old man who was diagnosed with alcoholic liver cirrhosis and type 2 diabetes when he was 50 years old. His drinking history was 540–720 mL Japanese sake per day for 35 years, and his smoking history was 30 cigarettes per day for 30 years. His ascites increased in 2008 when he was 57 years old, and he repeatedly exhibited symptoms of hepatic encephalopathy. Due to the liver cirrhosis symptoms, the patient was treated with several medications including furosemide, spironolactone, lactulose, and total amino acid preparation. To prevent the complications of liver cirrhosis, coil embolization to a portal venous shunt was performed twice. The patient was admitted to our hospital in June 2012 because of slowly progressive renal impairment and nephrotic syndrome.
Upon admission, the patient's height and weight were 166 cm and 64 kg, respectively. His body temperature was 36.7°C and his blood pressure was 150/60 mmHg. His consciousness was clear. His abdomen was slightly expanded but exhibited no tenderness. The liver and spleen were not palpable. No rash or purpura was noted on the skin. Diabetic and/or hypertensive changes were not observed in the ocular fundus.
The laboratory findings on admission were hemoglobin level of 9.4 g/dL (normal range 13.5–17.6 g/dL), platelet count of 11x104/μL (normal range, 13.1–36.2x104/μL), prothrombin time measurement of 68% (normal range, 70–130%), total bilirubin level of 0.9 mg/dL (normal range, 0.3–1.2 mg/dL), NH3 level of 85 mg/dL (normal range, 30–80 mg/dL), blood urea nitrogen level of 41 mg/dL (normal range, 8–20 mg/dL), serum creatinine concentration of 1.77 mg/dL (normal range, 0.5–1.1 mg/dL), serum total protein level of 5.7 g/dL (normal range, 6.7–8.3 g/dL), serum albumin level of 2.1 g/dL (normal range, 3.5–5.2 g/dL), total cholesterol of 188 mg/dL (normal range, 120–219 mg/dL), and HbA1c of 5.8% (normal range, 4.3–5.8%). The serum levels of IgG were 1558 mg/dL (normal range, 870–1700 mg/dL), of IgA were 481 mg/dL (normal range, 110–410 mg/dL), of IgA1 were 398 mg/dL (normal range, 50–314 mg/dL), of IgA2 were 83 mg/dL (normal range, 10–156 mg/dL), and of IgM were 219 mg/dL (normal range, 35–220 mg/dL). The serum levels of free κ and λ light chains were 149.0 mg/L (normal range, 3.3–19.4 mg/L) and 106.0 mg/L (normal range, 5.7–26.3 mg/L). The serum free light chain ratio was within normal range. The serum level of complement factor C3 was 79 mg/dL (normal range, 65–135 mg/dL), of C4 was 17 mg/dL (normal range, 13–35 mg/dL), and of CH50 was 41.1 U/mL (normal range, 30–50 U/mL). All of the other serology findings including anti-nuclear antibody, hepatitis B virus surface antigen, hepatitis C virus antibody, anti-neutrophil cytoplasmic antibody, and anti-glomerular basement membrane antibody were negative. There was no M-spike on serum and urine protein electrophoresis. A serum test for a cryoglobulin precipitation was negative.
The urinary sediments showed many red blood cells in high power fields together with granular casts and dysmorphic red blood cells. The urinary protein excretion was 4.7 g/day. The 24-hour creatinine clearance was 45 mL/min. Computed tomography revealed liver deformity with moderate accumulation of ascites. The kidneys were normal in size and there were no signs of urinary tract obstruction.
The renal biopsy specimens contained a total 28 glomeruli, 12 of which were globally sclerotic. The degree of interstitial fibrosis/tubular atrophy was 50–60% of the total biopsy specimen identified. Moderate fibrous intimal hyperplasia was observed in the arcuate artery. Diffuse segmental double-contours of the glomerular basement membrane and mesangial cell hypercellularity were identified in nonsclerotic glomeruli, exhibiting a membranoproliferative glomerulonephritis-like pattern (). Some glomeruli showed moderate-to-severe endocapillary hypercellularity, accompanied by fibrocellular crescents (). Fluorescent immunostaining showed granular staining of IgA and C3, but not of IgG, IgM, or C1q, on glomerular capillaries and some mesangial areas (Figures –). Among the IgA subtypes, staining of IgA1 (GenWay Biotech, San Diego, CA, USA) was observed, but staining of IgA2 (GenWay Biotech) was not identified (Figures and ). With light chain immunostaining, only κ (SouthernBiotech, Birmingham, AL, USA) was identified and no λ staining (SouthernBiotech) was seen (Figures and ). On electron microscopy, the glomerular capillary walls showed double contours. Electron-dense deposits were found in the paramesangium and around the subendothelial space of the glomeruli (). No organized structure deposits were identified (). Based on these findings, this case was histologically diagnosed as diffuse membranoproliferative glomerulonephritis with monoclonal IgA1-κ deposits.
Because this case was accompanied by moderately advanced decompensated liver cirrhosis, there was a concern that the patient may have serious side effects due to aggressive treatment such as the administration of corticosteroids. Thus, supportive treatment based on medications such as RAS inhibitors/diuretics, in addition to dietary therapy including salt restriction/branched-chain amino acid administration, was selected. Although these treatments led to a modest decrease in the urinary protein excretion, the patient's renal dysfunction slowly progressed and finally resulted in end-stage renal failure and initiation of dialysis therapy.
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pmc-6188763-1
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A 40-year-old female presented with chronic headache with infrequent exacerbations. She presents with worsening headache for three months with associated vertigo, nausea, and vomiting not responding to analgesics or vestibular sedatives. Her symptoms initially started twelve years ago as a diffused mild headache, which persisted through the day. Gradually, the headache worsened to a severe headache episodically associated with vertigo, nausea, and vomiting. These episodes lasted for two to three days and got resolved. She was treated with flunarizine for suspected basilar migraine but did not show any response. From the last year, she had monthly exacerbations of headache associated with distressing vertigo, unsteadiness of gait, and right-sided body numbness. In between these episodes, she had a significant dull diffuse headache not responding to simple analgesia. She did not complain of fever or night sweats but had constitutional symptoms lasting for several months. All of these symptoms severely affected her daily activities and functionality.
During the last 17 years, she had repeated episodes of neurological deficits. Even before the headache appeared, she has presented with visual impairment of the right eye and right lateral rectus palsy and was treated as retrobulbar neuritis with good response to methylprednisolone. One year later, she developed left-sided visual impairment, which fully responded to methylprednisolone. MRI imaging at that time revealed normal results. Few months after this event, she got admitted with right hemisensory loss with hemiplegia, and a demyelination disease or hemiplegic migraine was suspected. Second MRI was performed at this admission, and no abnormalities were detected again. Eight years ago, she had developed a left lower motor type facial nerve palsy, which was attributed to Bell's palsy. Within the last year, she was diagnosed to have depression and anxiety for which she was treated for few months. Other than the first two instances, she was not treated with steroids thereafter. She did not complain of weight loss and did not have constitutional symptoms or chest symptoms during these periods.
On examination, she is an averagely built female with a BMI of 23 kg/m2. She is afebrile, pale, and did not have lymphadenopathy. Her GCS was 15/15, and she was conscious and rational with normal pupillary response, visual acuity, visual field examination, and fundoscopy. There was no neck rigidity, and she had residual left lower motor VII palsy. She had an ataxic broad-based gait with unsteadiness. Upper and lower limb examination is clinically normal. Her respiratory, cardiovascular, and abdomen examinations were unremarkable.
Investigations revealed a hemoglobin count of 9 g/dL with normal white cells and platelets. ESR was elevated to 86 mm/1st hour. Renal- and liver-related biochemical investigations were normal with an alkaline phosphatase within the normal range. Initial MRI scans of the brain done 10 years ago did not reveal any abnormalities such as demyelination, optic nerve enhancement of focal lesions in the cerebrum, or cerebellum. CSF examination revealed an elevated protein level of 55 mg/dl with normal glucose and cells with negative oligoclonal bands or TB-PCR. Vasculitis investigations including ANA, ANCA (ELISA and Immunofluorescence), and RF were negative. Syphilis serology and HIV testing were also negative. Chest radiograph, ultrasound abdomen, and CT scan of chest and abdomen did not reveal any mediastinal lymphadenopathy or focal lesions in visceral organ or evidence of any malignancy. Serum ACE levels (19 µ/l) and ionized calcium levels were normal. We performed a new MRI scan of the brain with contrast, which revealed a diffuse and patchy meningeal thickening and enhancement mainly in the right frontoparietal and left occipital regions with a minor enhancement of bilateral optic sheaths (). Her NMO antibodies were normal, and the MRI did not show any areas of demyelination. Therefore, she underwent a dural biopsy from the thickened dura, which revealed large areas of caseous necrosis surrounded by epithelioid histiocytes and lymphoid cells with a few isolated giant cells in the adjacent vicinity (). There were no features of vasculitis or sarcoidosis. TB-PCR of tissue and acid-fast bacilli were negative. Final conclusion was necrotizing granulomatous inflammation suggestive of dural tuberculosis. This diagnosis was presumed by the presence of necrotizing granulomatous necrosis with caseation with a strongly positive Mantoux test of 25 mm (), and later was supported by a marked response to antituberculous medication.
We initiated her on antituberculous therapy (all four drugs for 3 months and 9 months of rifampicin and isoniazid) without streptomycin as she is already having vestibular symptoms. Steroids were added concurrently (1 mg/kg) and was continued for 6 weeks and was tailed off over a month. She experienced a marked improvement of her headache, and she could do her daily activities normally. After a year of anti-TB medication and follow-up, she did not complain of any worsening of symptoms.
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pmc-6188767-1
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We present the case of a 26-year-old female patient who developed severe persistent lower back pain secondary to spondylolisthesis in the fifth lumbar vertebra. Tramadol 50 mg dose was prescribed as a nonsurgical measure to achieve satisfactory analgesia. She took one 50 mg tablet and the pain was effectively controlled. However, she almost immediately noticed accelerated flow of speech and was unable to control her desire to talk incessantly. She was also quite overactive and “on the go” for the following four hours following intake of tramadol 50 mg dose. She noticed that she did not want to “sit still” and continued to walk to-and-fro and engaged in cleaning the house as she experienced increased energy. She was unable to sleep, although she experienced increased irritability with neither extreme happiness nor euphoria. She retook tramadol 50 mg twice 4 days and 7 days later and the same condition (overtalkativeness, overactivity, and distress) reoccurred upon both occasions lasting for exactly 4 hours each time. There was no ataxia, tremors, blurring of vision, or any other neurological signs or symptoms. She did not want to take tramadol anymore.
Notably, she had no previous psychiatric or neurological history of note. She took no psychotropic medications for any physical or psychological reasons. She had no history of illicit substance misuse or dependence.
Apart from spondylolisthesis, she suffered from urticaria and congenital optic disc tilt. She took Chlorzoxazone one tablet on request, ranitidine 150mg daily, and Desloratadine 10mg daily.
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pmc-6188772-1
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The patient is a 73-year-old male who was transferred from an outside hospital for repair of a right acetabulum fracture involving the femoral head after falling approximately 8-feet from a ladder while painting his house. Past medical history was significant for hyperlipidemia and osteoarthritis. Baseline metabolic equivalents were greater than four. Aside from a cataract extraction, the patient had no other operations. He denied any allergies. Prior to presentation, the patient was on Aspirin 81 mg daily for cardiovascular disease prevention and Atorvastatin 20 mg daily for hyperlipidemia. Computed tomography (CT) without contrast showed an acute, comminuted, and displaced fracture of the right acetabulum involving both posterior and anterior acetabular walls. The right femoral head was superiorly and laterally displaced with impaction fracture to its inferior and medial aspects. There were bone fragments within the right gluteus musculature, and the high attenuation in tissue density represented blood product within. Prior to surgery, the orthopedic team made an effort to reduce the patient's right acetabulum fracture with tibial traction pin under conscious sedation with midazolam, fentanyl, and ketamine in the emergency department. During the closed reduction, the patient experienced a brief period of respiratory depression. For approximately two minutes, his oxygen saturation was 85-86%, which improved to 95% with Narcan reversal. The emergency department record also noted that the patient had premature ventricular contractions on the electrocardiogram (EKG) at this time. After the closed reduction, the orthopedic team opted to monitor the patient on continuous telemetry for 24 hours and take the patient for open reduction and internal fixation of the right acetabulum the next day. He was not on prophylactic anticoagulation for this preoperative period.
Prior to entering the operating room, the patient's vital signs were stable: blood pressure 120/64, heart rate 73 beats per minute, respiratory rate 18 per minute, oxygen saturation 95%, and temperature 98.6 Fahrenheit. Neurological exam was significant for limited right knee flexion (<30 degrees). Otherwise, overall sensation was intact and right deep tendon reflex was intact. Hemoglobin was 11.6, down from 13.4 on admission. Coagulation tests showed elevated prothrombin time at 12.8, partial thromboplastin time 26.7, and international normalized ratio 1.20. In the OR, the patient was induced with standard dosing of midazolam, fentanyl, lidocaine, propofol, and succinylcholine. Phenylephrine was given preemptively on induction to avoid hypotension. Intubation was uncomplicated. Patient had two 20g peripheral intravenous catheter in place, and a left radial arterial line was placed after intubation. Despite premedication with phenylephrine, the patient became hypotensive with systolic blood pressure (SBP) in the 80s, median arterial pressure < 65. Boluses of ephedrine and phenylephrine were given, and a phenylephrine infusion was started thirty minutes after induction. The patient initially responded appropriately to treatment (SBP > 100). Due to concern for sciatic nerve injury, intraoperative somatosensory evoked potential (SSEP) monitoring was performed, and general anesthesia was maintained with propofol at 100 mcg/kg/min and remifentanil at 0.2 mcg/kg/min, in addition to 0.5% end tidal sevoflurane.
Upon patient positioning to the right lateral decubitus position from supine, the patient's SBP acutely declined into the 50s and the patient became hypoxic with an oxygen saturation of 88%. His hypotension was no longer responsive to phenylephrine or ephedrine. Norepinephrine and epinephrine drips were started. Also, the FiO2 was increased from 50% to 100%. There was a minimal and transient response to epinephrine administration. The patient was then returned to supine position, and he arrested shortly thereafter. Chest compressions commenced immediately upon loss of cardiac rhythm. The cardiac anesthesia team emergently responded and performed an intraoperative transesophageal echocardiography (TEE), which showed reduced left ventricular ejection fraction and reduced right ventricular systolic function. Due to unsuccessful cardiopulmonary resuscitation, the patient was placed on venoarterial ECMO via right femoral artery and vein; stable hemodynamics were achieved. A total of 8000 units of Heparin was given upon ECMO installation. At this point, the planned surgery was aborted. The patient was transported to the cardiac catheterization lab for pulmonary angiogram, cardiac catheterization, and antegrade perfusion of the right superficial femoral artery. A large thrombus in the left pulmonary artery was discovered on selective angiography (Figures –). Hypothermic protocol was initiated. Heparin therapy was also continued at this point.
On hospital day 5, a CT chest with contrast showed multiple bilateral pulmonary emboli and evidence of right ventricular failure. Right heart catheterization and placement of a Swan-Ganz catheter demonstrated that the patient was found to have severe pulmonary hypertension 55/30 and elevated central venous pressure (CVP) of 18. The patient underwent bilateral pulmonary artery embolectomy, exploration of right atrium with removal of clots, discontinuation of ECMO support, and repair of right femoral artery on hospital day 9. His pulmonary artery pressure and CVP improved to 31/12 and 8, respectively. One month later, the patient was discharged to a rehabilitation facility with a plan for conservative management of his fracture.
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pmc-6188774-1
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A 22-year-old woman with a history of diabetes mellitus (diagnosed at 7 years old) is treated with insulin glargine and with good adherence to treatment, with hypothyroidism and 2 previous ICU admissions due to diabetic ketoacidosis in which blood glucose levels were greater than 300 mg/dL.
The patient sought consultation due to vomiting and abdominal pain 12 hours after onset. Upon physical examination, the abdomen was distended with diffuse pain and no signs of peritoneal irritation. Laboratory results showed the following values: pH: 7.25; bicarbonate: 10 mEq/dL; BE: -14.9; blood glucose: 153 mg/dL and positive ketonemia. Admission laboratory results are shown in . Upon diagnosis of normoglycemic diabetic ketoacidosis, in the context of menstrual cycle alterations and with the aim of studying the trigger, beta subunit of human chorionic gonadotropin levels was requested: 98.928 IU/L. A transvaginal ultrasound was performed and showed a gestational sac with an embryo inside. Reanimation was started with parenteral crystalloids administered at 250 mL/h during 24 hrs. It was interspersed isotonic saline solutions and polyelectrolyte solutions. Total income is 7000 ml / 24 hs. Urinary volume is 2750 ml / 24 hs. Positive balance is 4250 ml/24 hs. Continuous insulin infusion was started, as described in literature (receiving a total of 100 IU in 48 hrs). Progress was shown with improvement of the clinical condition and lab monitoring every 8 hours: pH 7.47; bicarbonate of 22 mEq/dL with blood glucose levels in the normal range (< 200 mg/dl). The usual insulin glargine dose was restored and the patient was discharged.
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pmc-6188774-2
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A 50-year-old woman, former smoker, with a history of arterial hypertension, dyslipidemia, left side breast cancer which required chemotherapy, radiation therapy and surgery, hypothyroidism, and diabetes mellitus type II, is treated with 10 mg/day of Dapagliflozin, 1000 mg of Metformin every 12 hours, and NPH insulin at 40 and 60 IU. The patient sought consultation due to abdominal pain, diarrhea and fever. Upon admission, the patient was alert, tachypneic, and being with diffuse abdominal pain with no sign of peritoneal irritation. An abdominal ultrasound was requested and showed the gallbladder with multiple gallstones. The complete laboratory results are shown in . In the context of leukocytosis, acute kidney failure, and severe metabolic acidosis, the patient was admitted to the ICU with a diagnosis of sepsis. Due to the presence of metabolic acidosis with a gap of 32, a ketonemia test was requested. The result was positive and the patient was diagnosed with euglycemic diabetic ketoacidosis.
After starting treatment with a continuous insulin infusion pump and the administration of water, the patient was discharged from the hospital after 5 days.
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pmc-6188774-3
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A 74-year-old male patient with a history of arterial hypertension, noninsulin dependent diabetes mellitus medicated with oral hypoglycemic agents, ischemic cardiopathology with stent placement, nonoliguric chronic kidney failure, and cryptogenic liver cirrhosis required a liver transplant and subsequently suffered portal vein thrombosis requiring anticoagulation. The patient sought consultation after 3 days of passing liquid stools, together with emesis. He denied having fever spikes and, on that date, consulted the emergency ward of this institution, to which he was admitted feeling alert, with AT: 130/64, heart rate: 108 beats per minute, and SO2: 97% on room air. Upon physical examination, the patient was alert, tachypneic, and being with dry mucous membranes. Admission laboratory results are shown in . A ketonemia test was requested and the result was positive. The clinical presentation was interpreted as dehydration secondary to gastrointestinal losses and euglycemic diabetic ketoacidosis. Reanimation was started with crystalloids, a continuous insulin infusion pump, and the administration of intravenous bicarbonate. After 48 hrs, the patient presented DKA resolution criteria.
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pmc-6188852-1
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A 43-year-old male with past medical history of hypertension, depression, and an unspecified cardiomyopathy presented to the hospital with complaints of abdominal pain, distention, and nausea for 4 months, worse in recent weeks. The patient had multiple episodes of vomiting with inability to tolerate anything by mouth. His primary care doctor prescribed metoclopramide and famotidine, which provided minimal relief. In parallel to his GI symptoms, the patient also described symptoms of fatigue and worsening shortness of breath on exertion. He denied chest pain, palpitations, diarrhea, constipation, or increased swelling of the legs. The patient was a former cigarette smoker and drank alcohol socially.
On physical examination, there was jugular venous distention and trace peripheral edema. Auscultation of the lungs was significant for mildly diminished breath sounds in bilateral lower lobes with bibasilar crepitations. Cardiac auscultation was significant for a 2/6 holosystolic murmur of mitral and tricuspid regurgitation. Bowel sounds were normal. The abdomen was soft but mildly distended with diffuse tenderness. There was no guarding or rigidity.
Initial laboratory findings showed a B-type natriuretic peptide (BNP) of 1374 pg/ml consistent with volume overload. The basic metabolic panel was normal. Venous blood gas showed an elevated lactic acid level of 3.2 mmol/l suggesting tissue hypoperfusion. Complete blood count (CBC) and coagulation panel showed a platelet count of 66 K/Ul and an international normalized ratio (INR) of 2.3 (the patient was not taking anticoagulants prior to admission). These findings indicated some degree of liver dysfunction which was confirmed by abnormal liver function tests (LFTs) that showed an albumin of 3 g/dl, direct bilirubin of 1.9 mg/dl, total bilirubin of 4.0 mg/dl, aspartate aminotransferase of 98 IU/l, alanine aminotransferase of 121 IU/l, and an alkaline phosphatase of 87 IU/l. Chest radiograph showed cardiac enlargement. The patient was admitted for further workup of abdominal pain and management of acute decompensated heart failure.
Computerized tomography (CT) of the abdomen and pelvis with oral and intravenous (IV) contrast was performed showing wall thickening of the cardia of the stomach, a moderate amount of abdominal ascites, and diffuse anasarca and thickening within the proximal sigmoid colon (). Abdominal ultrasound (US) showed fatty infiltration of the liver and distention of the intrahepatic inferior vena cava (IVC) and hepatic veins. Echocardiogram (ECHO) showed a severely decreased left ventricular (LV) systolic function with ejection fraction (EF) of 21–25%. There was global cardiomyopathy, moderate LV diastolic dysfunction, and severe mitral and tricuspid valve regurgitation. The right ventricle (RV) was moderately dilated and hypokinetic. The patient's last known EF was reported to be 40% a year ago.
Cardiology evaluated the patient and recommended medical optimization and diuresis with plans for eventual right and left heart catheterization once he was euvolemic. Gastroenterology evaluated the patient for his abdominal pain, nausea, vomiting, and elevated LFTs. The patient's liver function was suggestive of cirrhosis. Viral hepatitis panel, iron studies, serum ceruloplasmin, alpha-1-antitrypsin, anti-mitochondrial antibodies, anti-smooth muscle antibodies, and anti-nuclear antibodies were unremarkable, ruling out infectious and autoimmune causes, making the etiology of his cirrhosis and abdominal complaints likely cardiogenic in origin.
Upper endoscopy was performed on hospital day 2 to rule out peptic ulcer disease as a cause of his nausea and vomiting, revealing desquamation of the esophageal mucosa in linear streaks and a large gastric bezoar obstructing the view of the underlying mucosa ().
After the endoscopy, the patient was given one can of Pepsi Cola and otherwise kept nil per os (NPO) for repeat endoscopy the following day with plans of possible bezoar removal. Repeat esophagogastroduodenoscopy (EGD) showed no evidence of the bezoar ().
Despite resolution of the bezoar, the patient continued to have complaints of intermittent nausea. Right and left heart catheterization was performed on hospital day 8, showing normal coronaries, reduced cardiac output, and mild pulmonary hypertension. It was suspected that the reason pulmonary pressures were noted to be lower than expected was because the patient had received aggressive dieresis in the days leading up to the catheterization and was relatively euvolemic.
His medications were optimized and he was fitted for a LifeVest prior to discharge from the hospital. After discharge, he underwent cardiac magnetic resonance imaging (CMR) which revealed a diagnosis of left ventricular noncompaction cardiomyopathy (LVNC) (). Cardiac output of the LV in cardiac MRI was measured to be 4.08 l/min with and EF of 28%. The RV was moderately dilated and noted to have an EF of 27%.
He also underwent a nuclear medicine gastric emptying study, which showed 24% gastric emptying at 90 minutes with the majority of the radioactive meal remaining in the proximal stomach. This study confirmed gastroparesis in our patient, presumably secondary to worsening cardiac function in the presence of biventricular failure due to noncompaction cardiomyopathy.
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pmc-6188857-1
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A seventy-four-year-old Caucasian man underwent the surgical excision of a cutaneous lesion of the back. The pathological diagnosis was superficial spreading MM, Clark level IV with a Breslow thickness 3 mm. MM cells appeared classically epithelioid and mitotic activity was less than 1 per 10 HPF. After two months, the patient underwent the left axillary satellite lymphadenectomy, which revealed the presence of metastasis from MM. Primary and metastatic tumours resulted diffusely positive to immunohistochemical staining for S100 and Melan-A (Ventana/Roche). Successive enlarged left axillary lymphadenectomy revealed an additional nodal metastasis. Two months later, a skin mass of 2 cm developed close to the previous surgical skin scar of the back. The clinical diagnosis was “in-transit” metastasis from MM. After surgical excision, macroscopic examination revealed a brownish-grey, multinodular, apparently circumscribed dermo-hypodermal mass, without haemorrhage or necrotic areas. Formalin-fixed paraffin sections, stained with haematoxylin-eosin, revealed a noncircumscribed, highly cellular dermal neoplasm, characterized by monotonous, slightly atypical spindle cells, arranged in storiform pattern, that deeply infiltrated subcutaneous tissue entrapping fat cells in a characteristic “honeycombing” pattern. A moderate mitotic activity (3 per 10 HPF) was recorded. Scattered heavily pigmented cells, with round to oval vesicular nuclei and dendritic cytoplasm, were also noted (). Immunohistochemical investigation of serial sections revealed that spindle cells were positive for vimentin and CD34, but negative for S100, whereas the pigmented dendritic cells resulted positive for S100, but also for Melan-A and HMB-45 (). Given those morphological and immunohistochemical features, a final diagnosis of BT was made. During the 18-month follow-up, the patient developed melanoma satellite skin metastases, multiple colliquative metastatic lymphoadenopathy (), metastatic nodules in lungs, liver, spleen and bones, to dorsal vertebrae, with compression of spinal cord at D5 level, and pelvis, microscopically similar to the first metastasis. The patient began immunotherapy with Ipilimumab 32 mg/kg for 4 doses, but died for neoplastic cachexia 18 months after the primary diagnosis.
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pmc-6189285-1
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A 41-year-old man presented with a headache for 1 day that predominantly affected the prefrontal and occipital regions. Persistent headache brought him into the hospital. He had no medical history of headache and hypertension and there was no history of head or neck trauma. Blood pressure was 200/140 mmHg on admission. He had no alterations in consciousness or visual symptoms. There were no hyperreflexia, ataxia, or other abnormal neurological examination results. Head computer tomography (CT) revealed no significant abnormities. Laboratory examinations showed a urine protein level of 2+ and 24-h urine protein was 1.06 g. Urine potassium and sodium were 39.25 and 315 mmol/24 h, respectively, demonstrating the impairment of renal function. Serum potassium was 3.23 mmol/L and serum sodium level was normal. The signal in the pons was increased in T2-weighted and fluid attenuated inversion recovery (FLAIR) image but was normal-intensity in T1-weighted images (Figures ). There were no abnormal signals in the parietal and occipital lobes (Figure ). Unfortunately, the patient did not receive diffusion-weighted imaging (DWI) on admission.
In consideration of his mild clinical manifestations (the severity of symptoms did not match the extent of his lesion) and normal neurological examinations, we excluded the diagnosis of brainstem infarction; also, the normal concentration of serum sodium may help to rule out the diagnosis of pontine myelinolysis. Then, we came to the diagnosis of PRES and initiated aggressive antihypertensive treatment with Irbesartan, Hydrochlorothiazide, Nifedipine, and Spironolactone. His symptoms completely resolved on the third day. A month later, repeated MRI showed complete resolution of the abnormalities in the brainstem (Figures ). Thus, the rare “reversible” characteristic of lesions following antihypertensive treatment confirmed the diagnosis of PRES.
This study was carried out in accordance with the approval of the Ethics Review Committee of Wuhan University Renmin Hospital. The subject gave written informed consent for the publication of clinical details in accordance with the Declaration of Helsinki.
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pmc-6189420-1
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An 11 year old girl originally presented with a 3 month history of diarrhea, weight loss, perianal skin tags and a labial abscess. Her centiles for weight and height were < 3rd and 25th centile respectively. Her diagnostic endoscopy and biopsies revealed ileocolonic ulceration and granulomatous inflammation, consistent with CD.She responded well to exclusive enteral nutrition (EEN) induction treatment and had sustained remission on thiopurine therapy for 18 months. She then had a symptomatic relapse, including a 10 kg weight loss, and was commenced on infliximab, an anti-TNFα monoclonal antibody, which re-induced and maintained remission until age 15 years. Her weight had improved from the 3rd to the 25th centile. Infliximab dosage and infusion intervals were optimized according to therapeutic drug monitoring results. At clinical review aged 15 1/2 years, she reported excellent health without any symptoms.Notably, her weight was < 3rd centile, and lab results included raised inflammatory markers and hypoalbuminemia. There was deep ileocolonic ulceration on repeat endoscopy but neither fibrostenotic nor fistulating disease on radiologic imaging. The patient was admitted, adalimumab was commenced instead of infliximab and EEN was commenced at 2,400 kcal per day. By day 10 of admission her weight had continued to fall and her BMI was 12.4 kg/m2. Biochemical work up revealed a hyponatremic, hypokalemic metabolic alkalosis. Due to concerns of non-compliance with EEN, 24-h “one-on-one” supervision was commenced. Within days her weight increased. Following multidisciplinary team engagement, she divulged she was “terrified of being overweight,” “hated” when she was in remission and felt “uncomfortable” when her weight was over 45 kg. She had been restricting her food intake and “idolized thin women” according to her mother. Following an adolescent psychiatry assessment, a diagnosis of AN was established. She ultimately required short-term parenteral nutrition until her disease stabilized and adequate feeding was re-established. She was discharged after 2 months of intensive child psychiatry and psychology input and has remained stable as an outpatient.
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pmc-6189630-1
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We report a rare case of human thelaziasis in a 6-month-old male child from the Rukum district (28o 38’16”N, 84o 27’17”E), Nepal. The district is at an altitude of 1581 meters above sea level, has a subtropical climate zone, an area of 2877 km2, and a population of 207290 (in 2011). The child is from a poor family, and he lives in a village where human and animals live in close proximity to each other. In this part of Nepal, people usually live in wooden houses where domestic cattle live on the ground floor and people live on the first floor. The patient was referred from a local eye hospital to an Ophthalmology clinic at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. His mother noted a whitish, motile, thread-like worm in the lower fornix of the conjunctiva of the right eye (). His mother also reported recent history of an insect (fly) sitting over the medial canthus of the right eye of the baby. Because the baby could not protect himself from the flies that sat on his eye, his mother reported that she came to the child, repeatedly leaving her household work, to wave the flies away from her baby’s eyes. On examination, it was noted that the child repeatedly rubbed his right eye. The patient was noted to have excessive lacrimation and conjunctival erythema and suffusion. No purulent discharge or trauma was noted. Visual acuity was within normal limits for age. Slit lamp examination was normal and did not demonstrate corneal abrasions, hypopyon, or retinal changes. A total of 6 worms were removed from the patient’s right eye. The worms were extracted from his right conjunctival sac by using a sterile cotton swab in our hospital, but 2 initial worms were removed by his mother with her bare finger. Ocular symptoms started to resolve rapidly after removal of the sixth worm. Of the 6 worms extracted, 4 were obtained for identification.
All 4 worms were identified as T callipaeda, 1 was male, and 3 were female. The worms were white, thin thread-like, and measured approximately 10–12 mm in length () in female and 7–8 mm in male. The female worm had a serrated cuticle, buccal capsule, mouth opening with a hexagonal profile ( and ) with a long muscular esophagus () and a conical tail with the vulva opening located at the anterior portion of the esophagointestinal junction ( and ). The vulva opening was visible under high magnification of light microscope as a slight bulges part near the mouth with a smooth surface free of cuticles () while tracing laterally from the anterior part. The alimentary canal was well distinguished from the reproductive system, which contained embryonated eggs in the proximal uterus and first-stage larvae in the distal uterus (). The anal opening of the worm was demonstrated at the caudal end. The male worm possessed similar buccal cavity but distinct esophageal-intestinal junction and characteristic curved tail end with shorter spicule with pre- and postcloacal papillae (). Based on morphological keys, collected nematodes were identified as T callipaeda. For further identification, the microscopic photographic evidence was forwarded to the Centers for Disease Control and Prevention (Atlanta, GA) and confirmed as T callipaeda, based on morphological keys.
The patient was admitted for observation for 3 days, and worms were not observed on serial ocular examinations. He was discharged with tobramycin ophthalmic drop to prevent secondary bacterial infection. Patient followed up occurred in 2 weeks. On follow-up examination, conjunctival congestion was resolved and ophthalmoscopic examination was within normal limits. No worms were observed during this examination.
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pmc-6189661-1
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A 57-year-old male patient, born and living in Hidalgo State, had suffered from hepatocellular carcinoma and underwent tumor surgery in June of 2017, followed by chemotherapy. He had been diabetic for 3 years, treated with metformin and glibenclamide, and showed poor control of blood glucose. He entered the general hospital of the Mezquital Ixmiquilpan Valley on April 25, 2018, with the diagnosis of acute abdomen and hypovolemic shock. This condition required resuscitation therapy and restitution of blood volume with crystalloid fluids. On the same day, an exploratory laparotomy was executed, finding hemoperitoneum of 2,000 mL caused by bleeding of the right lobe of the liver. Moreover, multiple adherences were observed of the omentum to the liver lobe, prompting the decision to perform perihepatic packing with plastic nonporous membrane. Another laparotomy had been programmed to take place in 24 hours. The patient was placed in the ICU and controlled with mechanical ventilation and inotropic and vasoactive drugs. The perihepatic packing was removed after 24 hours, revealing the persistence of bleeding. Consequently, the liver was again packed. On the first of May 2018, 30 whitish larvae with an average length of 1.1 cm were discovered in both nostrils. They were collected and sent to the entomology lab of the Institute of Diagnosis and Epidemiological Reference (InDRE, Instituto de Diagnóstico y Referencia Epidemiológicos) for taxonomical analysis. On May 2, the perihepatic packing was removed without complications, but the patient was in the grave condition with a poor short-term prognosis as a result of multiple organ dysfunction, which was the cause of death on May 15.
The taxonomical classification of the larvae of the third instar was based on the morphology of the cephaloskeleton, anterior spiracles (Figures and ), and peritreme plaques (). These organisms were identified as Lucilia sericata (Diptera: Calliphoridae).
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pmc-6189661-2
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A 24-day-old baby girl from Guerrero State was the product of the second gestation of an apparently healthy mother who underwent a normal pregnancy carried to full-term with vaginal delivery of a single product. The weight, height, and Apgar score of the newborn are unknown. The newborn was nursed by the mother for the first 7 days of life. At 10 days of age, the infant received an insect bite, which led to fever after 48 hours. The parents took the baby to the health center, where an infection of the respiratory tract and hyporexia were detected. Upon arrival, the baby was found in generally poor condition, weighing 2,220 g and suffering from severe dehydration. Intravenous feeding was begun immediately to stabilize the infant's condition, and subsequently, she was transferred to the Hospital of Indigenous Mothers and Children of Guerrero. At that facility, the baby arrived in a state of cardiac arrest, prompting cardiopulmonary resuscitation and phase III ventilatory support. Antibiotic treatment was given, and hydrotherapy was continued due to the presence of sepsis and septic shock. Two days posthospitalization, the presence of fly larvae was observed in both nostrils, giving rise to ivermectin treatment. Four whitish larvae were extracted, having an average length of 1.2 cm. They were sent to the Entomology Lab of the InDRE for taxonomical classification. The identification of the taxonomy of the larvae of second instar was based on the morphology of the cephaloskeleton, anterior spiracles (Figures and ), and peritreme plaques (). They remained an undefined Sarcophaga sp. (Diptera: Sarcophagidae), as the morphology did not correspond to any common or uncommon species known to cause myiasis. Diverse cases have been reported of traumatic and intestinal myiasis provoked by Sarcophaga sp., but the specific species has not been determined [].
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pmc-6189665-1
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A 52-years-old woman was hospitalized in the gynecological department due to recently diagnosed left ovarian cancer. Her medical history was unremarkable except from cigarrete smoking. Hematocrit was 38,1% and biochemical values of renal and hepatic function were within normal values. Tumor markers CA 15-3 was 39,5 U/ml (Normal Value (NV) <31,30), CA 19-9 was 104,93 U/ml (NV<37), and CA125 was 875,20 (NV<35 U/ml). A contrast-enhanced computed tomography (CT) of thorax was performed to exclude distal metastasis. It revealed a nonadherent thrombus of 20 mm long in the distal part of aortic arch (Figures and ). Immediate consult of vascular unit was scheduled and she was then referred to our department for further evaluation and treatment. Thrombophilia screen including Protein C, Protein S, Antithrombin III, APC Resistance-V, Factor VIII, homocysteine, and Anticardiolipin antibodies was performed which was negative. A transesophageal echocardiography was scheduled which showed a pedunculated free floating thrombus (FFT) 23 mm long of aortic arch (Figures and , ). The patient was commenced low molecular weight heparin therapy (LMWH) (enoxaparin, 8.000 units twice daily). Endovascular treatment was excluded since there was a high risk of distal embolization with manipulation of guidewires in the aortic arch and deployment of endograft. Open repair under extracorporeal cardiopulmonary bypass and hypothermic circulatory arrest from cardiothoracic surgeons was the second option but the patient unexpectedly denied fearing perioperative complications.
At the 8th day of her hospitalization patient experienced a sudden onset of pain in her left leg with incoming paresthesia and motion weakness. A provisional diagnosis of acute left leg ischemia was established and CT angiography of thoracic and abdominal aorta was performed which revealed complete dislodgement of thrombus from aortic arch which embolized as whole “thrombus” and thrombosis of left external iliac and common femoral artery (Figures and ). The patient was emergently transferred to the operation theatre where thromboembolectomy with Fogarty catheter was performed under local anesthesia. A histopathologic examination of the mass revealed the presence of exudative inflammatory cells (polymorphonuclear and lymphocytes) and fresh thrombus. No malignant cells were detected. The patient had an uneventful postoperative recovery and was discharged under enoxaparin, 8.000 units twice daily for at least one month in agreement with our Hemostasis specialist. During follow-up the patient remained asymptomatic and neoadjuvant chemotherapy was begun and operated for ovarian cancer 5 months later, under LMWH (Enoxaparin) 8.000 once a day.
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pmc-6189678-1
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The patient is an 11-year-old boy with Kleefstra syndrome whom we first evaluated in the endocrine clinic at 8 years of age for obesity to rule out Prader-Willi Syndrome. The patient is the male child of nonconsanguineous Guatemalan parents and was born at 41 weeks of gestation by spontaneous vaginal delivery to a 23-year-old, gravida 2, para 1 mother. The pregnancy was not complicated by any exposure to viral infection or medications. His siblings and both parents are healthy with no family history of miscarriages, stillbirths, congenital abnormalities, or learning difficulties. He was reportedly well until the 19th day of life when he presented with projectile vomiting and was diagnosed with pyloric stenosis. Surgery was uncomplicated; however, he had recurrent surgical site infections which required multiple readmissions.
In the interim, parents reported that he was able to walk at 3 years of age and had his first meaningful word (“Papa”) at 16 months. He attended special education classes and received speech, occupational, and physical therapy to address his developmental delays. He had recurrent acute otitis media managed with bilateral myringotomy. Audiologic evaluation also showed conductive hearing loss.
He was evaluated by endocrinology for the first time at age 8 years and 8 months. He was referred by his pediatrician for evaluation of obesity and hyperphagia which raised concern for possible Prader-Willi Syndrome. His height was 134.1 cm (64th percentile), weight 63.5 kg (>99th percentile), and BMI 35.31 kg/m2. Examination was remarkable for facial dysmorphisms (prominent eyebrows, low set ears, midfacial retrusion, and mild prognathism) (see ) and a genital exam that showed a micropenis. He was prepubertal with 3 cc testicles bilaterally, stretched penile length measured at 3 cm (-2.5 SD for age is 2.8 cm; mean is 6.3 cm), and no hypospadias. Laboratory tests showed LH <0.005 mIU/ml (normal 0.02-0.3), FSH 0.184 mIU/ml (normal 0.26-3), and testosterone 9 ng/dL (normal 2.5-10) (). Brain MRI was normal.
Due to the low gonadotropins associated with isolated micropenis, treatment was initiated via intramuscular testosterone cypionate injection of 50 mg given once a month for 3 months at the age of 9 years and 9 months. He had a normal response to testosterone injections with an improvement of stretched penile length to 5.5 cm (normal 6.3 ± 1.0 cm) after 4 doses. There were no noted adverse reactions to testosterone injections such as acne, fluid retention, decreased testicular size, or mood swings.
At 10 years and 9 months, GnRH agonist stimulation testing showed an LH-predominant response with peak LH of 11 mIU/mL and peak FSH of 4.3 mIU/mL at 24 hours. Testosterone rose from 48 ng/dL (normal <7-130 ng/dL) at baseline to 132 ng/dL at 48 hours (). hCG stimulation testing was done 1 month later for Leydig cell function assessment. shows that there was adequate testosterone biosynthesis (testosterone 300 ng/dL at 24 hours after the last dose of hCG) and no evidence of 5-alpha reductase deficiency (T:DHT 21.4; normal T:DHT <35) after the hCG stimulation test.
Genetics referral was initially made at 1 year of age due to global developmental delay, nontypical dysmorphic facial features, and the history of hypertrophic pyloric stenosis. There was no history of hypotonia, feeding difficulties, or seizures. Karyotype showed normal male (46, XY). Fragile X testing was normal. DNA oligonucleotide microarray study revealed a likely benign maternally inherited 563 kb duplication at 1p22.3. Rett syndrome, although rare in males, was ruled out at the age of 4 by sequencing and deletion/duplication analysis of the MECP2 gene. At 9 years of age, methylation study for Prader-Willi critical region was negative. Whole exome sequencing (WES) revealed a heterozygous de novo pathogenic variant c.2712+1G>A in the EHMT1 gene, which led to a diagnosis of Kleefstra syndrome. Mitochondrial DNA was sequenced as part of the WES with normal result. Developmental delays, dysmorphic facies, genital abnormalities, obesity, hearing loss, and recurrent infections are consistent with the diagnosis (see ). Screening tests for other associated phenotypic presentations were done. Echocardiogram and renal ultrasound were negative.
Follow-up exam at 11 years of age showed Tanner stage 3 pubic hair, testicular volume of 6 cc bilaterally, and stretched penile length 6 cm (normal 6.4 ± 1.1 cm). Parents deny any new behavioral changes, sleep disturbances, or seizures. He continues to follow up in the endocrine clinic for monitoring of pubertal progression and growth velocity.
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pmc-6189680-1
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A 55-year-old Japanese woman, gravida 2 para 2, underwent surgery for a tumor in the left ovary (11×13×12 cm). Laparotomy revealed the swelling of both ovaries, rectum involvement, and peritoneal dissemination from the pelvic cavity to the upper abdominal cavity. She underwent a hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and low-anterior resection of the rectum, which resulted in suboptimal surgery. Histological diagnosis confirmed high-grade serous carcinoma in the adnexal mass and peritoneal biopsy. She was diagnosed as stage IIIC ovarian cancer according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Six cycles of adjuvant chemotherapy combining paclitaxel (180 mg/m2) and carboplatin (area under the curve (AUC) = 5) were administrated every 3 weeks, and her serum levels of CA125 decreased to normal. Thirteen months after the end of therapy, the same regimen plus bevacizumab was added because relapse sites were confirmed in the pelvis and also her CA-125 levels were elevated. After three cycles of chemotherapy, the regimen was changed to doxorubicin (60 mg/m2) because of progressive disease. She developed dizziness, back pain, and severe headaches without neurologic signs after two cycles of the therapy, at forty-three months after the primary surgery. After hospitalization, physical and neurological examination showed normal results and no parenchymal lesion was detected on a contrast-enhanced CT scan of the cranium. Diagnostic lumbar puncture was performed the next day, which revealed carcinomatous cells of ovary origin in the cerebrospinal fluid (CSF) (). Magnetic resonance imaging (MRI) demonstrated abnormal hyperintensity in the cerebral sulci, mainly in the left lateral, occipital lobes, and folia in the cerebellar hemispheres and vermis on FLAIR with enhancement after gadolinium injection (). On the basis of these results, she was diagnosed with carcinomatous meningitis. High-dose corticosteroid therapy was begun, although systemic or intrathecal chemotherapy was not added because of her poor performance status. Her general condition and consciousness declined rapidly and she died forty-two days after the diagnosis. An autopsy was not performed.
The second case was a 63-year-old Japanese woman, gravida 2 para 2, with a history of hysterectomy because of fibroids at 45 years of age. A partially solid cystic tumor (5×4×6 cm) was detected in the pelvis at a private clinic. She was referred to our hospital for surgery. Her serum CA125 and CA19-9 levels were not elevated before surgery. Laparotomy revealed a tumor in the left ovary, and she was diagnosed as adenocarcinoma by frozen section without peritoneal lesions. The capsule of the tumor was intact and ascites was scanty. We performed bilateral salpingo-oophorectomy and omentectomy, resulting in compete surgery. Cytology of ascites was negative and the final pathological examination showed mucinous carcinoma limited to the left ovary (FIGO stage IA). After the surgery, she was followed up every 3–6 months at the outpatient department. After thirty-eight uneventful months, she developed headaches, dizziness, memory problems, and weakness of her left arm. A solitary tumor was found in the right lateral lobe (diameter 3 cm) on cranial MRI and a suspected relapse of the ovarian carcinoma was determined (). She underwent surgical resection of the cerebral lesion and pathological examination confirmed metastatic disease. Gamma-knife radiosurgery followed (49 Gy) without further chemotherapy. Four months after the brain surgery, she presented with nausea and vomiting caused by ileus. A CT scan revealed multiple recurrent tumors in the pelvic cavity. She underwent laparotomy, but we could not resect these multiple recurrent lesions, and colectomy was done to improve ileus. Postoperatively, we used chemotherapy combining paclitaxel (180 mg/m2) and carboplatin (AUC=5). Despite the therapy, she was diagnosed as a progressive disease after three cycles. At the same time, her performance status declined gradually without intracranial relapse and neurological symptoms. She succumbed to abdominal involvement nine months after resection of the cerebral lesion and no autopsy was performed.
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pmc-6189694-1
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A 35-year-old female was admitted to our outpatients' clinic with a compliant of an eight-month history of right heel pain which had increased gradually in the past two months. The pain of the patient often occurred at night and it was not related with daily or sporting activities and most commonly felt at rest. Her symptoms started insidiously and she did not mention any trauma. She had been smoking 20 cigarettes per day for 10 years, and she did not suffer from any medical condition. Furthermore, no hereditary disease was found in the patient's family history.
Physical examination revealed no abnormal findings. Her blood tests were all normal, including all the inflammatory markers. The patient underwent plain radiograph examination and a 21-millimeter-diameter cystic lesion was observed in the long axis of the calcaneus. The magnetic resonance imaging (MRI) examination was applied for the confirmation and it showed 22 × 20 mm intraosseous cystic lesion at the posterior part of the calcaneus which revealed hypointense signal on T1-weighted images and hyperintense signal on T2-weighted images (). The contrast-enhanced MRI was not available for this patient.
Although the lesion was radiologically benign, extended curettage and iliac bone grafting were planned to exclude the malignancy risk that may be caused by smoking history. The operation was performed under spinal anesthesia. After bone grafting from the right ilium was completed, tourniquet was applied to the right thigh. A lateral approach to the calcaneus was used. After opening a 10 × 10 mm valve from the lateral aspect of the calcaneus, the cyst was excised and the cyst walls were debrided by burr. After preparation of the area, the cavity was filled with bone grafts.
Microscopic examination revealed compact hypercellular areas with spindle cells which show nuclear palisading around fibrillary process in some areas. There was no mitotic activity. Diffuse expression of S-100 protein was observed with immunohistochemical staining, and Ki-67 proliferation index was observed around 5% at the highest level ().
In the presence of these findings, histopathologic diagnosis of the patient was reported as intraosseous schwannoma. Postoperatively, short leg splint was applied until the sutures were removed (). Ankle function exercises were begun at the second week after surgery. After 4 weeks of nonweight-bearing, she completely recovered with no pain at the end of the 2nd month.
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pmc-6190657-1
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A 51-year-old Japanese man who was born and raised in Japan and did not have any underlying medical condition presented with a rectal mass. He underwent endoscopic biopsy of the lesion, and the histopathological report showed spindle-shaped tumor cells with mild cytological atypia. Immunohistochemical analysis revealed that the tumor was positive for CD117 (c-kit) and CD34, leading to the diagnosis of a rectal GIST. He underwent colectomy after shrinking the tumor with 400 mg/day of imatinib for 9 months. After completion of treatment, annual follow-up computed tomography (CT) scans showed no local recurrence or distant internal organ metastases. His postoperative course was good and he could continue working as a judo therapist. There was nothing notable in his medical history, except for the rectal GIST, and he did not take any medication after surgery. His family history was uneventful and he did not smoke tobacco or drink alcohol.
Although he was asymptomatic, a CT scan 10 years after surgery revealed a destructive osteolytic lesion in the L3 vertebral body (Fig. ). CT-guided biopsy confirmed the lesions to be GIST metastases. His vital signs were stable with blood pressure 128/64, pulse rate 68 beats/minute, and temperature 36.3 °C. Sensations were normal in both lower limbs. His muscle strength was grade M5 throughout (Medical Research Council Scale of Muscle Strength), and deep tendon reflexes were normal. Laboratory testing showed a normal complete blood count (CBC). His liver and renal functions were sufficient, and the electrolytes were normal. As there were no metastases in vital organs and the tumor was located only in the anterior column of the vertebra, en bloc corpectomy of the L3 vertebral body was performed to provide local cure of the tumor and to prevent devastating sequelae of neural compression.
En bloc corpectomy via bilateral anterolateral retroperitoneal approaches was performed. Major vascular structures and the psoas muscles were retracted to expose the vertebral body and adjacent discs. The L3 vertebral body was cut off from the posterior elements using high-speed drills and chisels, and was removed en bloc. A titanium cage, with an autologous bone graft inside, was placed into the vertebral defect, and the spinal reconstruction procedure was finalized using screws and rods (Fig. ).
The pathological finding of the resected vertebral body was consistent with GIST metastasis, and the surgical margin was negative. Laboratory testing 3 days after the surgery showed slightly low hemoglobin (127 g/L, reference range 135–170 g/L) and a C-reactive protein (CRP) level of 114 mg/L (reference range < 3 mg/L). His liver enzymes were elevated: alanine aminotransferase (ALT) 112 U/L (reference range < 35 U/L) and aspartate aminotransferase (AST) 40 U/L (reference range < 35 U/L). CRP, ALT, and AST levels completely normalized within 1 month after surgery. In repeated laboratory tests, CBC, CRP, and liver enzymes remained normal until the final follow-up. At the 36-month follow-up, no local recurrence, new metastasis, or instrumentation failure was observed on CT or magnetic resonance imaging. He had full neurological functions without any limitation of daily activities.
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pmc-6190843-1
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On January 2003 a 56-year-old woman underwent total thyroidectomy for a multinodular goiter with a thyroid nodule that was suspicious for malignancy at cytology. No evidences of biochemical and/or ultrasonographic features of autoimmune thyroiditis were present before surgery (). The histological diagnosis was papillary thyroid carcinoma (PTC), classical variant (Figure ) but with focal areas of tall cells, perithyroid soft tissue invasion, and multifocality. Histology showed also the presence of a diffuse lymphocytic infiltration (Figure ).A few central compartment lymph node metastases were also present (Figure ) (pT3mN1aMx according to the 6th AJCC-TNM staging system) ().
On May 2003 the patient was referred to the Endocrine Oncology Unit of the Department of Clinical and Experimental Medicine of the University Hospital of Pisa to perform radioiodine remnant ablation (RRA) with 30 mCi of 131-I, after levothyroxine (L-T4) withdrawal. Post-therapeutic whole body scan (pWBS) showed an exclusive uptake in the central neck that was suggestive for thyroid remnant, serum thyroglobulin (Tg) was 1.2 ng/ml with undetectable levels of TgAb. On May 2004 the patient had undetectable Tg (i.e., <0.5 ng/ml) serum (Immulite 2000 Thyroglobulin; DPC, Los Angeles, CA) after the administration of recombinant human thyroid stimulating hormone (rhTSH; Thyrogen; Sanofi Genzyme, Cambridge, Massachusetts), negative TgAb (AIA-Pack 2000, Tosoh Corporation, Tokyo, Japan) and negative neck ultrasound (US). Considering the excellent response to the initial treatment the patient, accordingly to the American Thyroid Association guidelines (), was considered in clinical remission and then followed with clinical and biochemical (i.e., Tg and TgAb) controls and neck US every 12–24 months. The clinical evaluations, neck US and both Tg and TgAb were negative and/or undetectable for the following 5 years.
In 2012 an unexpected positive serum TgAb titer was noted still in the absence of detectable serum Tg. A small (8 mm) indeterminate lymph node was newly detected at neck US. The titer of TgAb slightly increased over the years and for this reason on August 2015 the patient was subjected to a computerized tomography (CT) scan that showed three small lesions (maximum diameter 12 mm) in the lung. A 18Fluorodeoxyglucose-Positron Emission Tomography (18FDG-PET) scan confirmed the presence of these lesions that were hypermetabolic (Figure ). On November 2015 the largest lung nodule, that was located in the inferior left lobe, was subjected to fine needle biopsy and cytology confirmed that cell morphology was suggestive of PTC (Figures ,). Moreover, the immunohistochemistry was positive for TTF-1 and focally for Tg (Figure ) and the measurement of Tg in the wash out of the needle used for the lung cytology was 1780 ng/ml, confirming the thyroid origin of the lesion. On December 2015 the serum Tg became slightly detectable and the patient was treated with 150 mCi of 131-I. The pWBS showed two areas of uptake in the lung that were suggestive of iodine avid lung metastases and likely corresponding to two of the lesions found at the CT and PET scan (Figure ).On May 2016 serum biomarkers, namely TgAb, continued to increase and the patient was subjected to a CT scan that showed a slight increase of the lung lesions (maximum diameter 14 mm). Taking into account the slow but continue increase of serum biomarkers on December 2016 the patient was treated with additional 150 mCi of 131-I. At that time the pWBS didn't show any radioiodine uptake. On February 2018 the CT scan showed a further increase in one lung lesion that reached a maximum diameter of 22 mm. A detailed history of serum biomarkers (i.e., Tg and TgAb) variation is summarized and shown in Table and Figure .
Paraffin embedded slices of the primary tumor tissue and cytological smears of the metastatic lung lesion were used for the DNA extraction that was targeted sequenced with a next generation sequencing system (Ion S5 deep sequencer, Ion Torrent, Applied Biosystem) by using a custom panel designed to analyze all thyroid related oncogene mutations. The analysis showed the presence of BRAF V600E mutation with an allelic frequency of 18 and 27% in the lung and primary tumor tissue, respectively. No other alterations were found with this analysis.
According to the Hospital rules, the patient signed an informed consent for the use of her clinical data and biological specimens for research purposes and publication of this case report; the study was approved by the Internal Review Board.
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pmc-6191007-1
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A 20-year-old male patient with autism and attention deficit hyperactivity disorder was transferred to our facility from a local hospital, after presenting with sudden onset of dark brown urine, non-bloody bilious vomiting, and painless watery diarrhea two days earlier. History was obtained from the patient's mother, as the patient was mostly nonverbal. His mother reported subjected fevers, but denied chest pain, shortness of breath, recent travels, or sick contacts.
On presentation to the local hospital, the patient was febrile (100.8 F), tachycardic (heart rate 111 and regular), and had an elevated blood pressure (148/87). Pulse oximetry was 84%-85% on 100% non-rebreather mask. Venous blood gas at that time showed pH 7.55, partial pressure of carbon dioxide (pCO2) 21, and partial pressure of oxygen (pO2) of 27, although the patient was lying comfortably in bed with a respiratory rate of 16. The other measurements were as follows: hemoglobin 11 g/dL, blood urea nitrogen 18 mg/dL, creatinine 0.3 mg/dL, total bilirubin 12 mg/dL, amylase 95 U/L, lipase 47 U/L, and lactic acid 2.7 mmol/L.
The patient was transferred to our hospital for admission to the critical care unit. Within hours of presentation, the patient became febrile with a maximum temperature of 100.7 F. On physical examination, the patient's sclera was icteric, hands were pale and jaundiced, and his lower lip was also jaundiced. His heart sounds were regular, abdomen was soft, non-tender and non-distended to palpation, with normoactive bowel sounds and no rebound, guarding or hepatosplenomegaly. Arterial blood gas was consistent with respiratory alkalosis: pH of 7.49, pO2 of 201, pCO2 of 27, bicarbonate of 20.3 mmol/L, and a base excess of -2.4 mmol/L. Methemoglobin level was 14%. His labs included hemoglobin 6.9 g/dL and hematocrit 21.2. The patient had leukocytosis (22.2 with 64% neutrophils), a platelet count of 145,000, creatinine level of 0.4 mg/dL, and glomerular filtration rate >60. His total bilirubin was elevated at 11.6 mg/dL (normal range 0.2-1 mg/dL). Alkaline phosphatase (40 U/L) and alanine aminotransferase (ALT) (21 U/L) were within normal limits. On presentation, his direct and indirect bilirubin, and aspartate aminotransferase (AST) levels could not be obtained as blood samples frequently hemolyzed, but subsequent studies the following day showed total bilirubin of 8.0 mg/dL with indirect hyperbilirubinemia (7.1 mg/dL), AST 117 U/L (normal range 5-40 U/L), and ALT 24 U/L. His hepatitis panel was negative, prothrombin time was 16.6 seconds, international normalized ratio was 1.3, and partial prothrombin time was 34.0 seconds. Urine analysis showed brown urine with +3 blood, +2 protein, +1 ketones, and a microscopic examination showed only 1-5 red blood cells. Glucose-6-phosphate-dehydrogenase (G6PD) was 10.2 U/gHb (normal range 5.5-20 U/gHb). Magnetic resonance cholangiopancreatography showed a distended gallbladder with no large filling defects or gallstones, normal intrahepatic bile ducts and common bile duct with no evidence of biliary obstruction, and normal pancreas. The patient was initially treated with supportive care—intravenous normal saline.
On Day 3 of admission, the patient was found unresponsive, diaphoretic, and tachycardic to 150 with oxygen saturation at 94% on room air. Hemoglobin was 3.6 g/dL, haptoglobin <10 mg/dL, reticulocyte count elevated 6.3%, and reticulocyte index 2.83. Lactate dehydrogenase was 2431 unit/L and total creatine kinase was 319 unit/L. Peripheral blood smear showed microcytes, macrocytes, Burr cells, Heinz bodies, bite cells, anisocytosis, and poikilocytosis (Figures -). Creatinine was also noted at 1.4 mg/dL, suggestive of acute kidney injury. The methemoglobin level was 10%, with carboxyhemoglobin level at 4.4%.
The patient was transfused four units of packed red blood cells with appropriate response to 9.4 g/dL. Respiratory support was provided with 5 liters nasal cannula with response oxygen saturation to 97%. Upon further questioning, the mother admitted that the patient was exposed to naphthalene mothballs, which she recently laid down in her home. The mode and amount of exposure was not known.
The patient was treated with intravenous normal saline and ascorbic acid (225 mg) orally three times a day. The patient began clinically improving and did not require inotropic support, intubation, or hemodialysis. Methylene blue was considered but was not given to the patient as the patient was clinically improving and methemoglobin levels were trending down. The patient was not oliguric during the hospital stay and continued to urinate copious amounts of dark brown urine, which improved to an amber color on the day of discharge. His hemoglobin remained stable between 9-10 g/dL after four units of packed red blood cells for the rest of his hospital stay. The methemoglobin level trended down to 2% on the day of discharge. Creatinine and total bilirubin trended down to 0.8 mg/dL and 2.2 mg/dL, respectively (Table ). The patient was discharged five days after admission with good outcome.
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pmc-6191008-1
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We present a case of 19-year-old male patient with no significant past medical history who presented with cough, greenish sputum, severe nausea, vomiting, and diarrhea for four days. It was associated with subconjunctival hemorrhage which prompted him to seek for emergent care. The patient reported sore throat for three weeks prior which was treated with over-the-counter cold medications. Initial vitals reported a temperature of 98.6°F, heart rate 82 beats per minute, blood pressure 156/85 mmHg, and respiratory rate 20 per minute. On physical exam, the oropharynx did not show erythema or exudates, no palpable lymphadenopathy. Chest and abdominal exams were benign. Labs showed white cell count 12,800/uL, hemoglobin 14.1 g/dL, and platelet 154,000/uL, sodium 133 mmol/L, potassium 4.5 mmol/L, chloride 97 mmol/L, bicarb 19 mmol/L, blood urea nitrogen (BUN) 95 mg/dL, creatinine 8.9 mg/dL, calcium 9.1 mg/dL, and liver function tests were normal. Urine analysis showed amber color urine, specific gravity >1.030, pH 5, protein >300 mg/dL, negative glucose, large blood, trace ketones, moderate bilirubin, negative nitrite, negative leukocytes, white blood cell (WBC) 10–25/HPF, red blood cell (RBC) 10–25/HPF, hyaline cast 10–25/LPF, and granular cast 0–2/LPF. Estimated 24-hour urinary protein excretion was 0.6 g/day. He was admitted and given volume resuscitation and broadly covered with antibiotics by his primary service. Nephrology was consulted in view of acute renal failure, proteinuria, and hematuria. Initial differential diagnoses of his acute kidney injury included PSGN, severe dehydration, IgA nephropathy, and vasculitis. Rapid strep A screening and throat swab culture were negative. C3 and C4 complements were <40 and <8 mg/dL, respectively. Total complement level was <10 U/mL. Anti-DNASE B antibody titer was 770 U/mL, and anti-streptolysin O titer was 285 IU/mL. Autoimmune workup was negative except antinuclear antibody titer of 1:160, and positive cryoglobulin with low cryoprecipitate. Computed tomography (CT) abdomen and pelvis without contrast showed small bilateral pleural effusions, no renal masses or obstruction as well as normal appearing ureters and bladder. With supportive measures, creatinine improved initially, but blood urea nitrogen got worse. On day three of admission, he developed pulmonary congestion and diuresis was tried without success. He subsequently developed uremic symptoms. Intermittent hemodialysis was started as supportive therapy for PSGN, volume overload, and uremic symptoms. In spite of aggressive conservative therapy, he continued to be hypoxemic with persistent bilateral pulmonary infiltrates. It was suspected that he had sequelae of pulmonary-renal syndrome despite negative serology. Thus, he underwent bronchoscopy and bronchoalveolar lavage which ruled out alveolar hemorrhage. He also underwent renal biopsy on day 22 of hospitalization. Renal biopsy identified acute tubular injury, enlarged glomeruli, endocapillary proliferation, neutrophils on light microscopy (Figure ), granular staining in capillary loops for C3 on direct immunofluorescence (Figure ), and subepithelial hump-like immune deposits on electron microscopy (Figure ). He had no evidence of tubular atrophy or interstitial fibrosis. The biopsy findings were consistent with PSGN. He was intubated for acute hypoxemic respiratory failure, and intravenous pulse dose steroids were initiated. He received three days of 1 g intravenous methylprednisolone followed by 500 mg daily for six days. The serum creatinine rapidly came down with daily improvement in urine output without further dialysis requirements. The trend of serum creatinine in relation to hemodialysis and steroids therapy is demonstrated in Figure . He was discharged with 20 days tapering course of oral prednisone. On the day of discharge, his serum creatinine was 1 mg/dL. On follow-up, renal function remained to be normal. He no longer required supplemental oxygen, and prednisone was tapered off. The degree of proteinuria and hypertension also improved significantly.
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pmc-6191010-1
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Patient 1 is a 65-year-old female with no smoking history and rare alcohol use who presented with a left tonsillar mass, confirmed as p16+ squamous cell carcinoma (SCC). She underwent left tonsillectomy via transoral robotic surgery and left neck dissection, revealing 2/21 involved lymph nodes (largest measuring 1.3 cm) without extracapsular extension. Lymphovascular invasion was indeterminate and perineural invasion was not identified. All deep and peripheral margins were free of invasive carcinoma. The closest margin from the left tonsil resection was 0.5 mm and was associated with a deep soft tissue margin on the lateral aspect. She was staged as pT2N2bM0.
The patient received adjuvant radiation therapy of 60 Gy to the tumor bed and ipsilateral neck and 54 Gy to the contralateral neck (Figure ). Subsequently, she experienced four sequential recurrences, including three endotracheal and one lung. Each was visualized on positron emission tomography/computed tomography (PET/CT) and pathologically confirmed as p16+ SCC, strongly suggesting metastases from the original tonsillar primary. (1) Thirteen months after the initial treatment (completion of adjuvant radiation therapy), she experienced a 7 mm endotracheal metastasis just inferior to the level of the thyroid isthmus, for which 4 cm of the trachea was resected with negative margins. (2) Two years after the initial treatment, she experienced a 6 mm endotracheal metastasis just inferior to the cricoid cartilage on the left and a 3 mm endotracheal metastasis just inferior to the right vocal cord, for which she received 66 Gy (Figure ), concurrently with cetuximab, after an incomplete resection. She also received 60 Gy and 54 Gy to a small portion of the trachea extending inferiorly. (3) Two and a half years after the initial treatment, she developed a 16 mm metastatic focus in the left lower lobe of the lung and malignant left hilar adenopathy, for which she received 60 Gy via proton beam therapy (Figure ), concurrently with carboplatin and paclitaxel. (4) Lastly, three years after the initial treatment, she developed an endotracheal metastasis 15 mm below the left vocal cord. She was scheduled for another tracheal resection but was lost to follow-up at our institution.
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pmc-6191010-2
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Patient 2 is a 62-year-old male with a 75-pack year smoking history and rare alcohol use who presented asymptomatically with a left neck mass, confirmed as SCC on biopsy. PET/CT showed hypermetabolic activity in the right aryepiglottic fold without corresponding CT findings and multiple involved ipsilateral lymph nodes. Routine workup with triple endoscopy revealed the aryepiglottic fold lesion, as well as <2 mm lesions in the carina and right/left mainstem bronchi, which were not distinct on PET/CT. A biopsy of each of these lesions revealed SCC, which stained positive for p40 and negative for TTF-1, confirming the tumor’s supraglottic origin. Testing for p16 was not performed because of the non-oropharyngeal primary. The patient was staged as cT2N2bM1.
The patient received definitive radiation therapy concurrently with weekly cisplatin. Intensity-modulated radiation therapy (IMRT) was used to deliver a total of 70 Gy to the aryepiglottic fold primary lesion, 60 Gy to the ipsilateral neck and the remainder of the larynx, 54 Gy to the contralateral neck, and 50 Gy to most of the tracheobronchial tree (Figure ). When treating the tracheobronchial tree, four-dimensional computed tomography (4DCT) simulation was used to define the internal target volume, which was expanded 0.5 cm volumetrically to form the clinical target volume and an additional 0.5 cm to form the planning target volume. Dosimetric parameters to select organs at risk (OARs) are shown in Table .
During treatment, the patient experienced grade 3 esophagitis, resulting in a 14 lb weight loss and requiring a feeding tube. Additionally, he was hospitalized with aspiration pneumonia. Nevertheless, he completed his radiation therapy without breaks.
Three months after chemoradiation therapy completion, PET/CT showed partial to complete resolution of hypermetabolic activity at the right supraglottic region, as well as partial to complete resolution of malignant cervical lymphadenopathy. He tolerated food exclusively by mouth. Ten months after the completion of therapy, the patient remained free of other treatment-related toxicities. Direct laryngoscopy at the time showed some thickening of the right aryepiglottic fold, but no concerning lesions, and bronchoscopy showed a resolution of the previously documented lesions in the carina and mainstem bronchi. Unfortunately, soon thereafter, the patient presented with abdominal pain and was found to have histologically confirmed liver metastases not previously seen on imaging. At his most recent follow-up visit 12 months after treatment completion, the supraglottis showed no evidence of disease.
Table summarizes and compares key clinical characteristics for patient 1 and patient 2.
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pmc-6191012-1
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A 25-year-old woman temporarily living in Grenada visited a local otolaryngologist presenting with a past history of Meniere’s disease without treatment (based on a lack of active symptoms such as tinnitus, vertigo, and hearing loss). On presentation, she expressed that the motivation behind the visit was to investigate the significance of her neck swelling. She had missed her period for two consecutive months. Routine examination showed a swelling over the right sternocleidomastoid muscle, midway along its anterior border (Figure ). The swelling was small, firm, subcutaneous, and partially attached to the skin. It had been present for as long as she could remember, with no associated symptoms. The history suggested a benign lesion consistent with the characteristics of a CCBR-choristoma.
Family history was unremarkable. No visible congenital anomalies such as aberrant implantation of the ears, auricular pits, auricular appendages, or fistulae were present. The swelling was about 0.75 cm in length x 0.5 cm in width. Palpation revealed a nontender structure in the subcutaneous plane unattached to the underlying tissue and mobile in every direction. The overlying skin was partially attached to the swelling, but it did not originate from within the skin (the skin above the swelling could be pinched up). No cervical lymph nodes draining the area were palpable. Examination of the left neck was unremarkable.
Due to her anxiety with respect to conceiving, and the risk of teratogenic radiological exposure, an ultrasound-based examination of the neck and cardio-abdomino-pelvic organs was performed to identify if her CCBR had associated defects. Ultrasound showed a hypoechoic (likely cartilaginous) mass measuring 0.94 cm x 0.43 cm (Figure ). Abdominal ultrasound and cardiac examination are recommended because of possible associated anomalies []. These anomalies must be taken into consideration, as there is marked variation in the reported prevalence of associated anomalies, ranging from 11% to 76% []. Thus ultrasound, being the least invasive diagnostic technique, while also serving the patient with maximum utility, was the modality of choice.
The patient did not request surgical excision, as she was asymptomatic with the lesion for the duration of her lifetime. She was told, and reassured, that the ultrasound examination showed a benign cartilaginous mass. The ultrasound of her heart, abdomen, and pelvic organs also showed no abnormalities. This diagnosis allowed the patient to feel some comfort after what she assumed could have affected the health of her baby.
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pmc-6191215-1
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A 59-year-old woman suffered from Tamai zone I amputation of her left second finger in an accident involving an automatic door at her workplace. Replantation was performed under general anesthesia (Fig. ). Using a light-emitting diode transilluminator, the recipient veins were visualized preoperatively. Two arteries, 1 vein, and 1 nerve were repaired. Postoperatively, the fingertip microcirculation was monitored using LSCI immediately after the operation and on the morning after the surgery for 3 days.
A Laser Speckle Contrast Imager (PeriCam PSI System; Perimed AB, Sweden) was placed approximately 20 cm above the patient’s hand to measure the perfusion of the fingertip (Fig. ). LSCI measures the perfusion by illuminating the tissue with a 785-nm-wavelength divergent laser beam. This creates a speckle pattern over the illuminated area. A CMOS camera captures the speckle image, while another captures a conventional color image of the measured area. The principle of this technique has been previously described in detail.
The distance between the camera and the patient’s hand was kept at 20 cm, and the image size was set to a 16 × 18-cm area. The frame rate was set to 6 images/s. With each measurement, the perfusion data from 60 consecutive images were averaged, resulting in a total measurement time of 10 s for each image. LSCI images were processed using the system analysis software program (PSIWin; Perimed AB). In each image, 5 circular regions of interest (ROIs) were selected in the left hand: the replanted second finger and the 4 other healthy fingertips. For each image, the average perfusion in each ROI was calculated.
The perfusion in the replanted second fingertip and the average perfusion of the 4 unaffected fingertips immediately after the operation was 93.5 and 229.36 perfusion units, respectively. The postoperative change in the skin perfusion measured by LSCI is presented in Figure .
The postoperative course was uneventful, and the perfusion measured with LSCI was stable during the observation period. The replanted fingertip survived successfully (Fig. ).
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pmc-6191803-1
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The patient was a 12-year-old boy who was referred for psychiatric evaluation as his mother was concerned with his complaints of hearing voices, low mood, suicidal attempts and refusal to eat. The first symptom, mother noticed was almost a year ago with patient wandering aimlessly for most part of day and his extremely limited diet intake. Later on, he started hearing voices in his head of two people who would talk about him among themselves. They would comment on how he performed his activities & give him commands. Initially, he tried to resist these voices but then got fearful that something bad would happen if he would not follow their commands. He also mentioned visual hallucinations for 3-4 months but when he was asked to elaborate, he refused to do so as” the voices are telling me not to tell”. The voices told him that other people knew what he was thinking. He began to think that people were talking with each other about him. He believes that his mother puts excess oil in his food in order to make him fat. The only way the voices in his head were reduced is by wandering around. He believed that the voices were eating his brain due to which he felt extremely fearful and immensely worried about his future.
He complained of low mood in the mornings and reported weeping spells on minor things in the past. His mother noticed social withdrawal. He has had suicidal thoughts with multiple suicide attempts. He tried to strangulate himself both times using his belt but loosened it when he felt asphyxiated. His suicidal attempts according to him were due to the command of the voices and also pressure from parents to eat more food.
He also had severe body image distortion and he was scared of putting on weight. His diet in last year was very restricted as he eats only low-calorie food such as bran bread and brown rice. He had imposed a low weight threshold on himself. His Body mass Index was 16.3 & weight was 36.6 kg, but he wanted to reduce it to 35 kg. There has been no history of excessive exercise except for walking around which he claims to do, so that he does not put on weight. No episodes of binge eating were reported. He planned to lose further weight by dietary restriction and avoidance of fattening foods.
On physical examination, he appeared to be cachectic. No lanugo hair, edema, parotid gland swelling or central nervous system abnormalities were observed. Secondary sexual characteristics were not developed. On mental status examination, he was well oriented in time, space and person. He was preoccupied with the voices in his head and fear of gaining weight. Many of the Schneider’s first rank symptoms were present. His mood was low and active suicidal thoughts were present. He mentioned feeling unsure whether he had a mental illness or not and vehemently denied any suggestions regarding him being underweight. Various Blood investigations such as complete blood count, liver function tests, thyroid function tests and random blood glucose were normal.
Comprehensive Psychological testing was done (including Kiddie Schedule for Affective Disorders and Schizophrenia, Child Behavior Checklist (CBCL), Personality Inventory for Child (PIC), Child Depression Rating Scale (CDRS) and Eating Attitude Test-40). The results of these tests along with the history and mental status examination further supplemented the diagnosis of Schizophrenia, Anorexia Nervosa and depressive symptoms. Delusions of control were evident in addition to auditory hallucinations. It is worth mentioning here that the client’s refusal to eat was not explained by the content of delusions and hallucinations. In addition, there was marked indication of unhappy family life along with presence of highly expressed emotions in the family. Mr. A.N.’s mother appeared as a rigid, authoritarian and controlling person; it was later reflected in her refusal to comply with the psychiatric advice.
His birth and milestones were reported as normal. He was having academic difficulties since the onset of illness. He was described by family as a loner with very few friends and poor social skills. There was family history of depression. Patient was given diagnosis of depression and Anorexia nervosa in past with antidepressant medications. He was never prescribed any antipsychotic medication.
The patient was recommended admission in an adolescent Psychiatric unit due to high suicide risk, regular monitoring of mental state examination and nutritional rehabilitation. He was prescribed Olanzapine 10mg daily and Escitalopram 10mg daily and was referred for psychological work, (both individual and family therapy). The family was psychoeducated but refused admission as they were in denial regarding the severity of illness and need for admission, regular monitoring and Psychopharmacological treatment. They showed ambivalence to the use of antipsychotic treatment and expressed wish to seek second opinion from abroad. At the last visit, family had started the medications but were planning to take patient to United States for treatment following which, he was lost to follow-up.
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pmc-6191892-1
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A 48-year-old man received a bilateral lung transplant for a diagnosis of desquamative interstitial pneumonia (DIP) that was attributed to smoking cigarettes and cannabis, both of which he ceased 20 months prior to transplantation. The diagnosis of DIP was based on compatible imaging and a prior surgical lung biopsy that was performed at the age of 44 years (Figs. and ).
The patient was diagnosed with HIV at the age of 38 years and had started HAART 20 months prior to transplantation at age 47. He achieved excellent control of his HIV infection, with a pre-transplant CD4+ cell count of 950 cells/μL, CD4+:CD8+ ratio of 0.69, no detectable viral load, and no history of AIDS-defining illnesses. His HIV was initially managed with cobicistat, elvitegravir, emtricitabine, and tenofovir, which were subsequently changed to abacavir, dolutegravir, and lamivudine when lung transplantation became a consideration due to pharmacokinetic interactions between cobicistat and tacrolimus [–].
The patient had progressively worsening dyspnea and lung function that prompted initiation of long-term prednisone and eventually mycophenolate mofetil (MMF), which were both prescribed in consultation with his HIV specialist. His interstitial lung disease continued to progress both clinically and radiographically (Fig. ), with pre-transplant lung function showing a forced expiratory volume in 1 s (FEV1) 55% predicted, forced vital capacity (FVC) 50% predicted, and diffusing capacity for carbon monoxide (DLCO) 36% predicted. Prior to transplant, he required 2 l oxygen via nasal prongs at rest.
His induction immunosuppression included basiliximab (20 mg on date of transplantation and post-operative day 4), methylprednisolone (500 mg at induction, 500 mg at reperfusion, and three doses of 125 mg on the day of transplant), and MMF (1 g pre-transplant). His explanted lungs still showed a pattern of DIP, but with a decreased number of airspace macrophages and a picture that in areas was more consistent with fibrotic nonspecific interstitial pneumonia (NSIP) (Fig. ). A similar progression of DIP to an NSIP-like picture has been reported previously [].
Post-transplant, his maintenance immunosuppression included MMF 1 g twice daily, prednisone 15 mg daily, and tacrolimus, dosed to a target trough level of 10-12 ng/mL. His previous HAART regimen was also continued. The patient had an uncomplicated course in hospital and was discharged from the intensive care unit on post-operative day 3 and discharged from hospital on day 18. He was maintained on daily valganciclovir 900 mg, trimethoprim-sulfamethoxazole 160-800 mg, and azithromycin 250 mg for prophylaxis against opportunistic infections. Valganciclovir was discontinued 6 months post-transplant as cytomegalovirus DNA remained undetectable in his serum. His tacrolimus trough levels were reduced to 8-10 ng/mL 10 months post-transplant. His prednisone dose was reduced to 10 mg and then subsequently 5 mg daily at 6- and 14-months post-transplant respectively.
He had an episode of Grade A1 minimal acute cellular rejection detected on surveillance transbronchial biopsy 3 months post-transplant. This was not treated, and there was no evidence of graft rejection on repeat biopsies 1 month later. He had an enterovirus/rhinovirus graft infection with significant allograft dysfunction 11 months post-transplant and received 3 daily doses of methylprednisolone 500 mg with a following prednisone dose of 60 mg daily, tapered by 5 mg every 5 days to a baseline dose of 10 mg thereafter. At the time of this infection, he also received a single dose of intravenous immunoglobulin 0.5 g/kg.
Post-transplant, the patient’s markers of HIV infection continue to be controlled, with CD4+ cell count nadir of 120 cells/μL on post-operative day 3. CD4+ count increased to 630 cells/μL at time of discharge from hospital, and was 940 cells/μL at 24 months post-transplant, with a CD4+:CD8+ ratio of 1.03, and undetectable viral load throughout (Fig. ). He continues to have normal functional status, no dyspnea, normal lung function, and normal ambulatory oxygenation 24 months post-transplantation.
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pmc-6191913-1
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A forty-three year-old, active duty, Caucasian male presented to our hospital with a complaint of acute onset dyspnea. His past medical history included post-traumatic stress disorder, chronic migraines, and a recent admission for prostatitis approximately five weeks prior. He was an active duty officer in the US Army, who was a non-smoker, a non-drinker, and who denied illicit drug use. His previous admission had been complicated by urinary retention necessitating the placement of a foley catheter. Urine culture at that time resulted with ten thousand colony forming units of viridans group streptococci identified through colony morphology and biochemical testing. As part of the laboratory’s standard operating procedure susceptibility testing was not performed in the absence of a physician request due to a bacterial colony count less than one hundred thousand. He was subsequently discharged home with a fourteen day course of empiric Levofloxacin 500 mg once daily.
On re-presentation, he denied the presence of genitourinary symptoms. Initial vital signs revealed blood pressure of 120/73 mmHg, pulse rate of 140 beats per minute, temperature of 99.4 degrees Fahrenheit, respiratory rate of 34 breaths per minute, and oxygen saturation of 94% on room air. Physical examination was notable for mild respiratory distress with supraclavicular retractions, tachycardia with new 3/6 holosystolic murmur, and pitting lower extremity edema. There was no evidence of splinter hemorrhages, Janeway lesions, or Osler nodes. The remainder of the physical examination was within normal limits. Notable laboratory results were as follows: leukocyte count 13.3 × 103, hemoglobin 8.1 g/dL, platelet count 150 × 103, C - reactive protein 11.5 mg/dL, erythrocyte sedimentation rate 68 mm/hr., troponin of 0.08 ng/mL, and renal function panel with an anion gap of 18. Radiographic studies included portable chest x-ray and chest CT scan revealing pulmonary edema and bilateral pleural effusions. The patient was started on empiric vancomycin and piperacillin-tazobactam antibiotic therapy. Despite hemodynamic stability at presentation, his cardiopulmonary status deteriorated over the course of six hours until the patient required vasopressor support and eventual intubation. Bedside transthoracic echocardiogram revealed a large, pedunculated, highly mobile echo dense mass involving the anterior mitral leaflet measuring 2.2 cm × 1.7 cm with associated severe mitral regurgitation. (Fig. ).
Due to the patient’s hemodynamic instability from acute heart failure from newly discovered cardiac vegetation on the mitral valve, the cardiothoracic surgery service took the patient to the operating room for an emergent mitral valve replacement. Intraoperatively, it was discovered that the vegetation involved mainly the anterolateral commissure (A1/P1 leaflets) but also extended into P2 and P3. There was also infectious involvement beyond the valve into the chordae. (Figs. , and ) Extensive intraoperative debridement was undertaken, the chordae to the posterior third leaflet were preserved, and the mitral valve was replaced with a 31 mm St. Jude mechanical valve. Following his surgery, the patient was transferred to the cardiac intensive care unit for convalescence.
Blood cultures initially obtained in the Emergency Department grew gram-positive cocci in clusters at approximately thirty-six hours. Identification of the bacteria was later confirmed as A. urinae by use of the bioMerieux Matrix Assisted Laser Desorption Ionization Time Of Flight (MALDI-TOF) utilizing the Vitek MS database. Species identification was accepted after meeting the greater than 85 % confidence value threshold. Antibiotic susceptibilities obtained via agar diffusion revealed a penicillin susceptible strain with 0.12mcg/ml by ETEST (bioMerieux). Ceftriaxone and vancomycin susceptibilities were obtained via Kirby Bauer susceptibility testing and revealed intermediate 2mcg/ml and susceptible results 1mcg/ml, respectively. No additional antibiotic susceptibility testing was performed. Tissue culture performed on the cardiac vegetation itself resulted in identical identification and susceptibilities. Urine cultures failed to grow any pathogen. With susceptibility results known, the antibiotic regimen was narrowed to a continuous infusion of penicillin G dosed at twenty-million units over twenty-four hours combined with once daily gentamicin dosed at 3 mg/kg. The patient’s post-operative course was uneventful. He remained inpatient for an additional ten days while undergoing diuresis and awaiting his oral warfarin to reach a therapeutic level. His intravenous antibiotic regimen was continued for a total of six weeks from date of first negative blood cultures. Follow-up transthoracic echocardiogram obtained at the completion of antibiotic therapy displayed an appropriately functioning prosthetic valve and preserved ventricular systolic function. In addition to antibiotic therapy, the patient was treated with a six-week course of cardiac rehabilitation.
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pmc-6191965-1
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A 15-year-old primigravida was admitted at gestational age of 33 weeks and 3 days by ultrasound scan with complaint of intermittent lower abdominal pain with no per vaginal bleeding. Her prenatal care was done regularly in our hospital and the routine prenatal tests (hemoglobin level, syphilis, human immunodeficiency virus serologies, bacteriuria, glucosuria, and proteinuria by urine test strips) were unremarkable and she was of blood group O Rhesus positive. Her blood pressure was in normal range for her three visits. There was no history of urinary tract infection, preeclampsia, or diabetes. There was no reported drug or food allergy. Of note is that her pregnancy was the consequence of rape.
On admission, her general condition was normal, with a height of 143 cm and weight of 52 kgs.
She was afebrile, not pale with no general edema, having no jaundice and her blood pressure was 100/60 mmHg and her pulse rate was 82 bpm. The abdominal examination revealed a gravid uterus with fundal length of 28 cm, longitudinal lie, and cephalic presentation. Fetal heart rate was normal with uterine contractions. On pelvic examination, vulva and vagina were normal. The cervix was firm, posterior, and long admitting a tip of finger. Fingers were stained with whitish discharge. The diagnosis of threatened preterm labor and urinary tract infection was made and the patient was treated by tocolysis therapy with intravenous salbutamol 1,5 mg in 500 ml dextrose 5% at the rate of 7 drops per minute, intravenous ampicillin 1 g two times a day, and intramuscular diclofenac 75 mg two times a day.
Investigations found her hemoglobin at 10.5 g/dl, while on other laboratory examination, urinalysis and vaginal swab were unremarkable.
On day 3, she was improving with no lower abdominal pain and the tocolysis was stopped.
However, on day 4, she complained of vulvar edema. Her blood pressure was 110/80 mmHg, fetal heart rate in normal range with no palpable uterine contractions. On pelvic examination, the vulva was edematous and the diagnosis of vulvitis was suggested. Intravenous gentamycin 80 mg two times a day and oral metronidazole 500 mg three times a day were added on her treatment for 5 days, plus oral ibuprofen 400 mg two times a day as intramuscular diclofenac was already stopped.
On day 6, the swelling was getting worst despite the treatment and the patient had persistent vulvar pain with difficulty in ambulation and dysuria (). Her vital signs were in normal range. Some laboratory tests were requested (the white blood cells were 4,400/mm3, the albuminuria was negative, and the random blood sugar was 82,4 mg/dl) and an obstetrical ultrasound scan revealed a single live, intrauterine fetus at 33 weeks and 6 days. The patient was then treated with intravenous ceftriaxone 1 g two times a day for 7 days, dexamethasone 12 mg once a day for 5 days, and diclofenac suppositories 100 mg two times a day for 3 days as she was in severe pain and ibuprofen was stopped. A urinary catheter was inserted with difficultly due to the edema, to allow easy drainage and the urine output was in the normal range ().
Under the above treatment, she progressively improved and on day 10, the patient was doing well without swelling of the vulva () and the urinary catheter was removed. She was kept on ward until the onset of labor at term and for close monitoring.
She delivered at 39 weeks and 3 days by spontaneous vaginal delivery a live newborn boy, with weight of 2360 g and Apgar score of 9 at the first minute and 10 at the fifth minute.
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pmc-6192002-1
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A 67-year-old Sri Lankan woman was referred by a general practitioner to evaluate high erythrocyte sedimentation rate (ESR) incidentally detected while investigating for acute febrile illness. On admission to the ward she was asymptomatic. There was no history of prolonged fever, altered bowel habits, myalgia, or arthralgia; there was no history of backache, or urinary or bowel symptoms. No significant weight changes or change in appetite were noted. A symptomatic evaluation and systemic review was found to be normal.
She had been previously diagnosed as having hypertension, dyslipidemia, bronchial asthma, and osteoarthritis of bilateral knee joints. Her prescribed medication was rosuvastatin 5 mg taken at night with hydrochlorothiazide 25 mg taken in the morning, and glucosamine sulfate preparation and Ecosprin (aspirin) 100 mg taken at night. Two years before this presentation she presented to a surgical department with a history of painful neck lump and was found to have cervical lymph adenopathy which was biopsied under local anesthesia. The histological appearance favored granulomatous inflammation without caseation. Atypical mycobacterial infection/fungal granulomata/TB with superadded pyogenic infection were considered for the differential diagnoses. She was given category 1 antiTB medications and managed as TB lymphadenitis; treatment continued for 6 months and was completed in liaison with a pulmonologist.
During the current admission a complete blood count (CBC) showed evidence of mild anemia. Her hemoglobin level was 9.1 g/dl; her mean corpuscular volume (MCV) was 86.5 fl, mean corpuscular hemoglobin (MCH) was 27.8 pg, and mean corpuscular hemoglobin concentration (MCHC) was 31.4 g/dl. A direct blood film examination showed normocytic normochromic, mildly hypochromic microcytic anemia. Mild anisopoikilocytosis was noted. Her white blood cell count (WBC) was normal in number and found to have lymphocytes predominance. However, there were no features of lymphoproliferative disorder. Mild eosinophilia and plasmacytoid lymphocytes were seen. Platelet count and morphology was normal. Her ESR was 102 mm/hour and was persistently high throughout the period of evaluation. Her C-reactive protein (CRP) was within normal range. Baseline liver and renal profiles were normal. Urine Bence Jones proteins were negative. A skeletal survey did not reveal any abnormality. A chest X-ray was normal and sputum for acid-fast bacilli (AFB) was negative. Lactate dehydrogenase level in serum was normal. Serum protein electrophoresis indicated elevated alpha fraction, beta 2 fraction, and polyclonal increase of gamma fraction. Urine analysis had evidence of pyuria but culture was sterile. Urine for AFB was negative. As she was asymptomatic and screening was negative she was discharged from the ward and followed up as an out-patient.
A month after discharge she presented with fever and recurrence of lymphadenopathy to a local chest clinic and a biopsy revealed noncaseating granulomata. Immunohistochemistry did not reveal any evidence of hematological malignancy. A TB polymerase chain reaction (PCR) was negative. She was started on category 1 anti-TB treatment.
While on antiTB treatment for 2 months she was admitted to this hospital with history of symmetrical arthritis of bilateral hands and legs, persisting intermittent low grade fever without chills or rigors, and backache. She complained that both large and small joints were painful and swollen. She was diaphoretic and had vomiting, severe loss of appetite, and excessive sweating. She did not have any history of rashes. She had no history of jaundice.
On examination she was febrile, diaphoretic. Bilateral extremity edema was noted but her joints were not inflamed. Abdominal, chest, cardiac, and neurological examinations were normal.
Her ESR was 130; in CBC, her WBC was 12,000 with 82% neutrophils. Her CRP was 200. Her creatine phosphokinase (CPK) level was normal. Possible sepsis was suspected and she was started on intravenously administered ceftriaxone. Her serum calcium level, acetylcholine esterase level, and a magnetic resonance imaging (MRI) of her whole spine were normal. Baseline renal and liver profiles were normal except for mild elevation of transaminases. AOSD, sarcoidosis, polymyalgia rheumatic spectrum disorder, and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome were taken in a differential diagnosis and further evaluated. A cerebrospinal fluid (CSF) full report did not show any evidence of neurosarcoidosis, TB PCR/culture was negative, and purified protein derivative (PPD) skin test was less than 5 mm. Her antinuclear antibody (ANA)/rheumatoid factor (RF) was negative. Extractable nuclear antigen profile including anti-U1 ribonucleoprotein (RNP) was negative. CSF, serial blood cultures, and serial urine cultures were sterile. Peripheral blood rapid infection detection and PCR amplification for known bacterial and fungal species were done and found to be negative for trace DNA/RNA. Serum ferritin was mildly elevated. Antibiotics were changed in liaison with microbiology team into meropenem and vancomycin and continued for 10 days without success. Persistent fever with raised inflammatory markers was noted even after 3 weeks. Transthoracic and transesophageal echocardiography were normal. Hepatitis serology, retroviral screening, antibody against cytomegalovirus (CMV), and Epstein–Barr virus (EBV) were done and found to be negative. Contrast-enhanced computed tomography (CECT) of her chest and abdomen was done and no evidence of TB or fungal infections was identified. Upper gastrointestinal endoscopy, colonoscopy, and serial ultrasonography were normal.
After extensive diagnostic workup, finally we came to a conclusion and she was diagnosed based on Yamaguchi criteria as having AOSD presenting with granulomatous lymphadenopathy; she was started on intravenously administered methylprednisolone pulse therapy 500 mg, 250 mg, and 250 mg in 3 consecutive days followed by low-dose maintenance steroids and her condition remarkably improved. Her disease remission was characterized by resolving lymphadenopathy, normalization of inflammatory markers, and dramatically improving clinical symptoms. She was discharged for follow-up as an out-patient as she was in disease remission. She was reevaluated after 6 months and 1 year and reported no additional problems and she was doing her normal everyday life.
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pmc-6192067-1
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A 38 year old newly diagnosed HIV-infected, ART naive Malawian male presented to Queen Elizabeth Central Hospital, a large teaching hospital in Blantyre, Malawi. He reported a 2 week history of headache and vomiting. He had no past medical history of smoking, hypertension or diabetes. On examination, his blood pressure was 122/80 mmHg, pulse 124 beats/min and temperature 36.7 °C. He had a Glasgow Coma Score (GCS) of 15/15, there was evidence of meningism but no focal neurological deficit. A lumbar puncture (Additional file : Table S1) showed a WCC (white cell count) 6.0 × 106/μL, glucose < 2.22 mmol/L (normal range 2.22–4.44 mmol/L), protein 1.68 g/L (normal range 0.15–0.45 g/L) and a positive lateral flow assay for cryptococcal antigen (crAg; IMMY, Norman, OK) (Additional file : Table S1). Cerebrospinal fluid (CSF) opening pressure was 28 cm H20 (normal range 5–20 cm H20). Quantitative cryptococcal culture (QCC) demonstrated 740,000 colony forming units (cfu) /ml (normal < 0 cfu/ml). CD4 count at admission was 29 cells/μl, Hb 11.6 g/dL, WCC 7.5 103/μL, lymphocytes 0.9 103/μL. A diagnosis of CM was made and the patient started on 1200 mg fluconazole once daily and flucytosine 25 mg/kg four times daily as part of the Advancing Cryptococcal Treatment for Africa (ACTA) clinical trial (Open label, multicentre randomised trial; trial no. ISRCTN45035509). The patient received 14 days of treatment as an inpatient as per protocol. He required twice daily lumbar punctures until day 7 to manage his persistently raised intra-cranial pressure (ICP). His day 7 QCC was 22,300 cfu/ml and his QCC prior to discharge on day 14 was 30 cfu/ml.
The patient re-presented 5 days post discharge with recurrence of severe headaches, neck pain, drowsiness and vomiting. On examination, he had a GCS (Glasgow coma scale) of 15/15 and had no neurological deficit. CSF opening pressure was 28 cm H20 and his CSF was crAg positive, WCC 0 106/μL, glucose 2.88 mmol/L and protein 1.22 g/L (Additional file : Table S1). The patient was commenced on amphotericin to treat suspected CM relapse whilst awaiting cryptococcal culture. The culture was subsequently negative and amphotericin was discontinued. He continued on 800 mg fluconazole once daily and was discharged 19 days later with no ongoing symptoms of meningitis. ART was started according to national guidelines (TDF/3TC/EFV) at day 39.
The patient re-presented to hospital at day 54 (16 days post ART commencement) with recurrence of headache and fever, and a sudden onset of left sided weakness. He reported adherence to his fluconazole and ART. On examination, temperature was 38.2 °C, blood pressure 135/92 mmHg, pulse 89 beats/min, respiratory rate 22 breaths/min. He had a new left sided hemiparesis involving both the upper limb and lower limb (power 4/5 using the Medical Research Council (MRC) scale), and there was no sensory deficit. The CSF opening pressure was 21 cm H20. The CSF crAg remained positive, CSF WCC 0 106/μL, CSF protein was high, 3.26 g/L. Culture remained negative (Additional file : Table S1).
His peripheral CD4 count had increased from a baseline of 29 cells/μl to 198 cells/μl. Magnetic Resonance Imaging (MRI) of the brain (performed on day 5 of symptom onset) demonstrated multi-focal DWI positive lesions in the right corona radiata (Fig. ), right posterior limb of the internal capsule, right cerebral peduncle and 1 month later, the right caudate nucleus; these changes were consistent with an acute ischemic stroke. There was high T2 signal without DWI restricted diffusion in the right brainstem and left deep white matter, suggesting previous ischemia. The MRI findings and raised CSF protein in the context of rapid immune reconstitution, following an earlier favorable clinical and microbiological response to anti-fungal treatment and a sterile CSF is consistent with paradoxical C-IRIS as opposed to acute CM infection. Because of the involvement of both anterior and posterior circulation, this met the criteria for probable cerebral vasculitis12. The 0.35 T GE MRI scanner used, does not support an ADC sequence. However, given the sudden onset of the symptoms, these focal DWI changes, in the corresponding anatomical location, occurring within a vascular territory, the etiology is unlikely to be anything other than vascular.
The development of an ischemic stroke was considered to be either a late manifestation of the CM infection or due to intensification of HIV- or CM- associated inflammation with immune reconstitution8. Fluconazole at a dose of 400 mg was continued with ART and the patient achieved good functional improvement. Corticosteroids were not given.
An MRI scan performed one month later demonstrated maturation of the ischemic stroke (Fig. ), and a new DWI lesion in the right caudate, consistent with C-IRIS. The patient however reported complete resolution of the left sided weakness and remained well at day 185.
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pmc-6192079-1
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A 19-year-old, white female patient was referred to the oral and maxillofacial surgery department at the Federal University of Paraná as she complained regarding her aesthetics and malocclusion. Facial analysis showed a well-positioned maxilla despite a hypodivergent face pattern, with a reduction of tooth exposure upon smiling, and favorable chin projection associated with accentuated and deep labiomental fold due to retrusion of the inferior alveolar segment (Figures and ). There was also a shortening of the lower third of the face. There was no transversal deformity. Preoperative imaging exams showed a favorable position of the maxilla associated with good inclination of maxillary and mandibular incisors. A class II malocclusion with a deep bite in association with accentuated curve of Spee (COS) was found. The chin (pogonion) was well positioned (). The lower third molar was extracted six months before the time of orthognathic surgery. Different treatment options to correct the mandibular retrusion were offered to the patient: bilateral sagittal split ramus osteotomy (BSSO) associated with backward genioplasty or total subapical mandibular osteotomy (TMAO) which would keep the chin in position and eliminate the need for genioplasty. Another option was combined orthognathic surgery on the mandible with BSSO or TMAO, associated with forward and downward repositioning of the maxilla. The patient chose the total subapical mandibular osteotomy procedure only.
After 39 months of orthodontic treatment, surgery was performed under general anesthesia. After a local bupivacaine 0.5% infiltration, a “V” incision was conducted from the right to the left retromolar region, and a mucoperiosteal flap was carefully detached to maintain the mental nerve integrity (). A ring of cortical bone was removed around the mental foramen, aiming to create a space around it. A gradual and careful removal of the buccal cortical bone with a drill, exposing the inferior alveolar neurovascular bundle and letting it free in all of its extension from the foramen to retromolar region, was done (), different from the original technique []. Once the inferior alveolar neurovascular bundle was viewed in its entirety, it was carefully removed from the inferior dental canal and repositioned either inferiorly or superiorly. After the repositioning, a reciprocate saw was carefully used to conduct an osteotomy from the mental foramen to the retromolar region to divide the lingual cortical bone from the basal bone, taking care to avoid damage to the posterior teeth's apices (). The posterior vertical cut on the posterior body area behind the second molar was also done with 5 mm to safety margin of the tooth. The osteotomy was conducted until the parasymphyseal region, through the buccal and lingual plates, approximately 5 mm below the apices of the anterior teeth, taking care not to damage them. It is crucial to avoid as much possible damage to the lingual mucosa when cutting the lingual cortical bone due to the fact that it is the main pedicle supplying nutrition to the dentoalveolar segment after the osteotomy is completed (). After the dentoalveolar segment containing the entire lower dentition was mobilized, it was repositioned to the desired site and stabilized with miniplates and screws of the system 2.0. The conducted incision was closed with absorbable sutures (). Panoramic radiograph and cephalometric radiograph showed occlusal stability as well as the condyle in the right position after surgery (). Postoperative orthodontics consisted of intercuspidation and adjustment of the COS, since an intentional open bite in the bicuspid area was left during surgery to allow increase of the anterior facial height. The patient finished orthodontic treatment after 12 months. In , it is possible to observe the measurements obtained from the lateral radiograph, pre- and postoperatively. Improvement in the measurements related to overjet, facial axis, jaw angle, inferior sulcus to H-line, and occlusal plane is noteworthy.
The six-year follow-up showed stability of the osteotomized segments with maintenance of plates and screws. Occlusal stability was also observed, associated with a 49 mm mouth opening. The labiomental sulcus was observed to be less deep in comparison to the preoperative stage. Patient reported of paresthesia in the mental region, which was expected, due to incisal nerve sectioning. The resolution of the main aesthetic complaint of the patient, which was a deep labiomental sulcus, was achieved through the TMAO (Figures , , and ).
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pmc-6192110-1
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A 70 year old woman with a history of B-Cell Chronic Lymphocytic Leukemia (B-CLL) presented with a several week history of progressive right upper extremity weakness and increasing confusion. She had no prior history of cardiac surgery or cardiac abnormalities. Pertinent physical exam findings included a normal cardiac exam and 3/5 strength in the right arm. She was afebrile and her white cell count was at her baseline but markedly elevated (> 170 × 103/μL).
The initial workup was focused on the patient’s neurologic complaints. A brain MRI revealed multiple bilateral rim-enhancing brain lesions with surrounding vasogenic edema. The differential diagnosis included embolic or metastatic lesions, with a high suspicion for metastatic disease given the patient’s presentation and history. Workup for primary malignancy was negative, and the patient subsequently underwent a right craniotomy for biopsy. The resected lesion was found contain necrotic tissue with branching fungal hyphae suggestive of Aspergillus. Tissue cultures revealed Aspergillus Fumigatus species. IV Voraconazole (6 mg/kg every 12 h day 1 then 4 mg/kg every 12 h) and Micafungin (100 mg daily) were started. The Galactomannan assay was positive but all blood cultures were negative. A 2D echocardiogram was performed to evaluate for possible embolic source for the brain abscesses. This revealed a 1.3 × 1.1 cm pedunculated mass in the inferior wall of the left ventricle (Fig. ). There was no evidence of any cardiac dysfunction and the LV ejection fraction was measured at 55%. Cardiac surgery was consulted and the patient underwent median sternotomy with cardiopulmonary bypass for removal of the left ventricular mass using a left atriotomy incision. The mitral valve was first inspected through the atriotomy incision and demonstrated no vegetations. Subsequently, a retractor was placed through the mitral valve and the left ventricular mass was easily identified. A 1 cm soft, smooth appearing mass was found adhered to the inferior septal portion of the left ventricle with surrounding inflammation(Fig. ). It drained a small amount of purulent material which had to be suctioned. The mass was then removed and the involved cardiac muscle was debrided. There was no cardiac valve or papillary muscle involvement. Pathology and cultures again demonstrated growth of Aspergillus Fumigatus (Fig. ).
The patient awakened and responded appropriately following surgery but remained in the ICU. She subsequently developed multi organ failure secondary to gram negative sepsis and expired on post-operative day 17 and day 30 of IV antifungal therapy.
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pmc-6192125-1
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A 65-year-old Gurung Nepalese woman from a remote hilly area, a farmer by occupation, presented with painless bulging of her left eyeball of 2 months’ duration with recent progressive diminution of vision for 15 days. There was no significant family or past medical history. Her general appearance was fair and her Glasgow Coma Scale (GCS) was 15/15. During the admission, her pulse rate was 86 beats/minute, respiratory rate was 24/minute, blood pressure was 100/70 mm Hg, and temperature was 36.9 °C (98.4 °F). There was no lymphadenopathy. On local examination, she had proptosis of her left eye with visual impairment (visual acuity 6/18) but the ocular motility was normal (Fig. ). The contralateral eye was normal. No other abnormalities were found on neurological examination. A complete blood count showed normal parameters including hemoglobin 110 gm/L, total white blood cell (WBC) count 6.5 × 109/L, total red blood cell (RBC) count 4.25 × 1012/L, and total platelet count 399 × 109/L with differential count of 70% neutrophils and 30% lymphocytes. Her urine analysis was within normal limits with 1–2 WBC per high power field and 4–6 epithelial cells per high power field. She had normal renal function test with blood urea and serum creatinine of 4.49 mmol/L and 0.0796 mmol/L, respectively. Her random blood sugar was 5.1 mmol/L. The electrolytes, that is, Na+ and K+, were 147 and 4.2 mEq/L respectively. Her liver function tests were within normal limits with gamma glutamyl transferase (GGT) of 2.03 μkat/L, total protein of 58 gm/L, albumin of 36 gm/L, globulin of 22 gm/L, albumin to globulin ratio (A:G) ratio of 1.64:1, total bilirubin of 5.13 μmol/L, conjugated bilirubin of 1.71 μmol/L, unconjugated bilirubin of 3.42 μmol/L, aspartate aminotransferase (AST) of 0.53 μkat/L, alanine aminotransferase (ALT) of 0.43 μkat/L, and alkaline phosphatase of 2.03 μkat/L. Routine chest radiography was normal. Computed tomography (CT) of her head and orbit revealed a multiloculated cystic lesion involving the left infratemporal fossa and extending to the extraconal space of left orbit through the infraorbital fissure and causing erosions of left orbital bones (Fig. ). Magnetic resonance imaging (MRI) showed a well-defined multiloculated cystic lesion within the infratemporal fossa eroding lateral wall of maxillary sinus and floor of the medial cranial fossa. The lesion was hypointense in T1-weighted images and hyperintense in T2-weighted images. The eyeball was displaced antero-medially by the cyst (Fig. ). Radiological differentials were soft tissue mass and ameloblastoma.
She underwent surgery and intraoperatively, multiple cystic lesions eroding the surrounding orbital bones and extending to the infratemporal fossa were noted. Surgical removal of the cysts with left lateral orbitectomy and decompression of the left optic nerve were done. The specimen was received for histopathological examination; it consisted of multiple translucent cysts, the largest measuring 2 × 2 cm and filled with clear fluid (Fig. ) along with two separate bony bits. The larger bony bit measured 3 × 2 × 1 cm and showed tiny whitish cysts closely attached to and infiltrating into the bone. On microscopy, acellular laminated eosinophilic structures with inner germinal layer were seen infiltrating into the bony trabeculae. The surrounding areas showed foreign body giant cell reaction and fibrosis (Fig. ). It was reported as hydatid cyst infiltrating into the orbital bone. Ultrasonography (USG) of her abdomen was performed which did not show any visceral involvement. She was advised albendazole on discharge but was lost to follow up. She again presented after 15 months with left orbital swelling. She underwent a CT scan which showed recurrent hydatidosis. On enquiry, she revealed that she did not take oral albendazole as prescribed. No visceral involvement was seen on repeat USG of her abdomen. She underwent repeat surgery with left lateral orbitectomy and decompressive multiloculated cystic lesion in the left infratemporal fossa. After surgery, she was administered tablet albendazole 400 mg twice daily for a period of 28 days. She is now free of disease 6-months postoperatively.
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pmc-6192131-1
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In June 2002, a 36-year-old woman presented to her primary health care doctor with a history of flushing, diarrhoea, night sweats, and a clinically detectable mass in her left medial supraclavicular fossa. Her past medical history consisted only of essential hypertension for which she did not require prescribed therapy. Her family history included a brother with a diagnosis of sarcoma and two other non-first-degree relatives with primary brain malignancies.
Fine needle aspiration confirmed the diagnosis of medullary thyroid cancer, and in July 2002, she underwent total thyroidectomy with left-sided modified radical neck dissection and central compartment clearance. At this point, concerns were raised regarding optimal cytoreduction as the appearances of the central compartment, level 4 and level 5 nodes, were that of extensive disease. In order to maximise local disease control, she received adjuvant radical radiotherapy delivering 60 Gy to the thyroid bed.
Two years after completion of treatment, in February 2004, follow-up repeat imaging reported a recurrent nodule at level 4 of her neck. Subsequent resection confirmed this to be recurrent medullary thyroid cancer with no evidence of distant spread at the time. She continued to be monitored at the oncology clinic and remained disease-free until four years later, in May 2008, when computer tomography (CT) imaging revealed new pulmonary parenchymal metastases. These were closely monitored for the next 2 years with repeat imaging and measurement of calcitonin levels. In May 2010, it was decided that the patient should embark on systemic anticancer treatment.
She was offered participation in a phase 2 clinical trial with the agent lenvatinib (E7080) and she commenced treatment with 24 mg once daily in May 2010. One week into therapy, it was noted that she was marginally hypertensive with a blood pressure of 140/100 mmHg. No proteinuria was identified at this point, but she was commenced on 5 mg of amlodipine to manage hypertension. Monitoring of blood pressure and urinalysis continued as per study protocol.
After two completed cycles of lenvatinib, CT imaging reported a reduction in size of all lesions. Further tumour assessment after 4 months confirmed a partial response to treatment with a 50% reduction of the sum of the long diameters of target lesions. She was experiencing various grade 1 toxicities throughout this time but was keen to maintain treatment given the good response. Due to the multiple low-grade toxicities, the dose of lenvatinib was initially reduced to 20 mg and thereafter to 14 mg.
In December 2011, 19 months after starting lenvatinib, she developed mild ankle oedema. Urinalysis carried out at the time identified proteinuria. A subsequent 24-hour urine collection identified 3.1 g/litre of proteinuria, equating to a urinary protein creatinine ratio (UPCR) of 625. The patient had not started any other medications and the incidence of proteinuria was felt to be lenvatinib related. Treatment with lenvatinib was ceased; however, due to concerns regarding possible intrinsic renal disease, she underwent screening for glomerulonephritis which was negative.
A subsequent renal biopsy showed focal segmental glomerulosclerosis (FSGS) in two of twelve viable glomeruli, with tuft-capsule adhesion, hyalinosis, segmental intracapillary hypercellularity, and segmental splitting of capillary walls, predominantly in regions of segmental sclerosis. There was mild tubular atrophy, interstitial fibrosis, mild/moderate arterial intimal fibroelastic thickening, and mild arteriolosclerosis. Immunofluorescence showed no staining in glomeruli. Electron microscopy showed mild patchy reduplication of the basement membrane and effacement of only 20% of podocyte foot processes. There were no widespread electron dense deposits and no endothelial cell tubule-reticular inclusions. The endothelial cells showed no evidence of activation or damage. The appearances were consistent with a diagnosis of focal segmental glomerulosclerosis (FSGS). The lack of widespread podocyte foot process effacement suggests a secondary form of FSGS, which in the context of anti-VEGF treatment, could be mediated by microangiopathy. Whilst there was no histological evidence of acute thrombotic microangiopathy, it is possible that some of the pathological changes seen (splitting of glomerular capillary walls and mild arteriosclerosis) could be related to chronic low-grade endothelial cell damage. Based on histology, it is not possible to be certain whether the FSGS was caused by direct podocyte injury or whether it was related to endothelial cell injury. Histological slides are illustrated below in Figures , , and .
Throughout this time, excretory function remained stable. Treatment with an ACE-inhibitor (ACEi) was introduced but due to poor tolerance and the quick improvement of the proteinuria after cessation of lenvatinib, the ACEi was stopped and patient's blood pressure was monitored closely.
Withdrawal of lenvatinib had a marked effect on the levels of proteinuria, as illustrated in .
The patient continued follow-up at the renal clinic on a regular basis until July 2013, when she was discharged with no evidence of proteinuria, normotensive and with normal excretory renal function.
After her discharge from the renal clinic and between 2013 and 2017, the patient was treated with vandetanib, nintedanib, and cabozantinib with no evidence of recurrent renal disease.
E7080, also known as lenvatinib, is a potent inhibitor of the receptor protein kinases VEGFR-2 and VEGFR-3 but also displays inhibitory binding properties against VGFR-1, FGFR-1, and PDGFRα/β, albeit at significantly higher IC50 (half maximal inhibitory concentration, IC50). Its ability to restrain angiogenesis was shown on human umbilical vein endothelial cells (HUVEC) where E7080 inhibited VEGFR-2 phosphorylation and thereby capillary tube formation []. Apart from angiogenesis, E7080 decreased lymphangiogenesis in both the primary tumour of human breast adenocarcinoma cells in xenografts as well as in metastatic nodules in the lymph nodes of nude mice bearing these tumours []. Glen et al. showed in preclinical experiments that abrogation of FGFR and PDGFR signalling by E7080 inhibited invasion and migration of human melanoma cells lines (DX3) and human osteosarcoma epithelial cells (U2OS) []. Its potency against FGFR-1 differentiates E7080 from other currently approved tyrosine kinase inhibitors with antiangiogenesis properties [, ].
The preclinical data above were confirmed in several early phase human trials with E7080 in 2011 and 2012 in US, Europe, and Japan. Whilst establishing pharmacokinetic and pharmacodynamic properties of the drug, safety and preliminary efficacy was also well described. Lenvatinib was well tolerated at doses from 10 mg BID to 25 mg OD [–] and was associated with a reduction in disease activity biomarkers [], partial response, and stable disease according to response evaluation criteria in solid tumours []. These findings were further established in phase 2 trials and notably responses were demonstrated in thyroid cancer [–].
Approval in thyroid cancer was granted in light of significant improvement in progression-free survival (PFS) compared with placebo in patients with radioiodine-refractory differentiated thyroid cancer in a phase 3 study (SELECT study) []. Lenvatinib improved median PFS over placebo by almost 15 months (HR 0.21; p < 0.01) and induced an objective response rate of 64.8%. The median survival results were diluted due to crossover of the patients from the placebo arm to the treatment arm; nevertheless, a subgroup analysis on patients stratified by age showed that older patients (>71 years old) had a survival advantage when treated with lenvatinib compared to placebo (HR, 0.53; p = 0.02), and the younger subgroup achieved a PFS of 20.2 months versus 3.7 m (p < 0.001) [].
Proteinuria and hypertension are the two most commonly reported side-effects of VEGF inhibitors and frequently the cause for therapy discontinuation. Proteinuria is used as a surrogate marker for glomerular damage and hypertension often accompanies and aggravates this.
The pathophysiology of proteinuria and glomerular damage in anti-VEGF therapy remains complex and far from well understood. Biopsy-proven cases of glomerular disease in anti-VEGF therapy are few; however, most have demonstrated changes in keeping with glomerular thrombotic microangiopathy (TMA) histology, with predominant endotheliosis and membranoproliferative changes [, ]. Other histological changes documented include cryoglobulinaemic glomerulonephritis, acute interstitial nephritis, collapsing and crescentic glomerulonephropathies, and FSGS plus TMA [–].
It has been theorized that hypertension is caused by decreased vascular production of nitrous oxide induced by inhibiting VEGF. This leads to renal haemodynamic compromise and subsequent proteinuria (much akin to exercise-related proteinuria) []. However, a mouse model study showed that glomerular injury preceded hypertension [] and many cases document glomerular injury in the absence of hypertension [], indicating that it cannot be the only trigger for proteinuria in anti-VEGF treated patients.
Inhibition of VEGF in podocytes (by injection of anti-VEGF antibodies or VEGF gene deletion) results in loss of endothelial fenestrations in glomerular capillaries, proliferation of glomerular endothelial cells, loss of podocytes, and proteinuria in mice [, ]. VEGF appears to be a crucial endothelial survival factor and its inhibition often manifests as TMA, a histology strikingly similar to that of severe preeclampsia—as placenta overproduces a soluble VEGF receptor (fms-like tyrosine kinase 1) that acts as a VEGF antagonist.
Izzedine et al.'s 8-year follow-up study results from 2014 shed great light in anti-VEGF-related renal injury. It showed that in 100 patients who developed renal disease whilst on anti-VEGF treatment, the main histology associated with TKIs was minimal change disease and/or collapsing-like focal segmental glomerulosclerosis (MCN/cFSGS), a FSGC variant which is considered a separate entity to FSGS. In the same analysis, TMA histology was most frequently associated with VEGF-ligand targeted therapy (such as bevacizumab and aflibercept) suggesting two, possibly distinct pathophysiologies [, ] between renal damage caused by targeting the VEGF ligand as opposed to targeting the VEGFR tyrosine kinase domain. This could potentially be explained by considering the associations and signal transduction pathways between podocytes, endothelial cells, and VEGF. Podocytes produce vascular endothelial growth factor (VEGF), whereas VEGF receptor tyrosine kinases (RTKs) are expressed by both podocytes and glomerular endothelial cells.
Our case demonstrates a secondary form of FSGS pathology which cannot confidently be attributed to TMA but could potentially represent the end result of chronic low-grade endothelial cell damage. The moderate histological findings were in keeping with a less-severe clinical course of the FSGS, with fast resolution of proteinuria and hypertension. More significantly, rechallenging the patient with additional three agents blocking the VEGF axis did not result in recurrence of the renal damage.
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pmc-6192132-1
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A 60-year-old female with history of ovarian cancer, doxorubicin-induced dilated cardiomyopathy, and advanced heart failure had a Medtronic cardiac resynchronization-defibrillator (CRT-D) device placed in May 2010. The patient had implantation of HeartWare LVAD for destination therapy in August 2011 due to progression of heart failure and functional decline. The postsurgical course was complicated by ventricular tachycardia and multiple episodes of pump thrombosis. Interrogation of the CRT-D device in December 2011 (as well as subsequent device checks) revealed that the patient had evidence of complete heart block with no escape rhythm at ventricular backup rate of 40 ( EKG). The CRT-D pulse generator was changed to a St. Jude Medical Assura model (3357-40C CRT-D) device in June 2014 once it reached its elective replacement indicator.
The patient was admitted to our hospital in November 2015 with concern for LVAD thrombosis. On this admission, the patient was treated with tissue-plasminogen activator (tPA) without improvement and was taken to the operating room for LVAD pump exchange on admission day 6. In the immediate postoperative period, it was noted that the patient's ICD was no longer consistently pacing. This prompted placement of epicardial pacing leads.
Device interrogation revealed stable right ventricle (RV), left ventricle (LV), and shock lead impedances. The RV lead pace threshold was increased to 1.75 V at 0.5 ms (previously <1 V at 0.5 ms), while the LV lead pace threshold was stable at 0.75 at 0.5 ms. There was a continuous external noise with a mean amplitude of 1 mV detected by the ventricular sense amplifier of the RV lead. The intracardiac electrograms (IEGMs) showed an increase in a baseline noise signal compared to prior device-based recordings—the amplitude of which correlated with the increase of the LVAD pump rotation speed. The device was reprogrammed to nonsensing mode (DOO) allowing consistent pacer function of the ICD ( IEGM). These setting changes meant that the tachytherapy function of the ICD was mandatorily disabled, as the device was set to a nonsensing mode.
The EMI oversensing issue was resolved by turning off the “low-frequency attenuation” (LFA) filter, which had resulted in amplification of the high-frequency VAD signal. This allowed the device to function in a sensing/tracking mode (DDD) without inhibition by noise from the LVAD with RV sensitivity threshold of 0.3 mV and permitted functional tachytherapy.
The LFA filter is a proprietary option in St. Jude Medical devices that suppresses low-frequency signals with the intent to mitigate T-wave oversensing. As with any “band-pass filter,” in addition to attenuating specific frequencies, they may also enhance or amplify other event frequencies, such as EMI, myopotential, R-waves, and far P-waves. The new VAD cannula position/orientation resulted in injection of the EMI signal more efficiently in the sensing antenna of the existing ICD lead. Additionally, the “sensibility” setting on the St. Jude device decays to baseline maximum sensitivity just prior to the A paced event—thus explaining why EMI was most consistently sensed in this window.
The patient underwent a successful defibrillation threshold (DFT) testing 10 days after her VAD exchange surgery. DFT testing showed that the ICD detected VF adequately with minimal dropout at a minimal sensitivity test setting of 1 mV. There was no further problem with the ICD, and the patient was discharged home one week later.
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pmc-6192136-1
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A 23-year-old male from Cameroon presented with acute-onset, right-sided scrotal pain and swelling while in the US for military training. He denied current or prior sexual activity, associated penile discharge, hematuria, fevers night sweats, weight loss, or cough. Urinalysis revealed pyuria, follow-on culture was not performed, and urine nucleic acid amplification testing (NAAT) was negative for Neisseria gonorrhoeae and Chlamydia trachomatis. He was diagnosed with acute epididymitis and treated with ceftriaxone and doxycycline. His symptoms improved, only to recur 6 weeks later, prompting a repeat ultrasound that revealed persistent epididymitis. Repeat urinalysis (no culture) and gonorrhea and chlamydia NAAT were negative. He was given an empiric 30-day course of ciprofloxacin, which improved the pain, but the swelling persisted.
Five months after his initial evaluation, he returned with another recurrence of symptoms. Physical exam again revealed prominent right-sided scrotal swelling and tenderness. An ultrasound demonstrated right-sided epididymitis with possible necrosis, increasing complexity of the associated hydrocele, and new concerns for a focal scrotal abscess. This was further evaluated with a contrasted computed tomography (CT) of the chest, abdomen, and pelvis, which revealed a complex right-sided scrotal fluid collection () in addition to an enlarged and heterogeneous prostate, an enlarged juxtaesophageal lymph node, and right lung apical nodular scarring. Although TB was considered in the differential diagnosis, a unilateral orchiectomy was performed, as malignancy was also high on the differential given his age.
Grossly, the epididymis was enlarged (6.0 × 1.7 × 1.5 cm; ), with caseating necrosis and miliary deposits within the testicle and epididymis (). There was an accompanying large scrotal abscess. The histologic sections showed diffuse necrotizing granulomas, with giant cell formation in the scrotum, testis, and epididymis (). The testicular parenchyma stained positive for acid-fast bacilli (AFB), and a surgical-scrotal aspirate NAAT using the GeneXpert MTB/RIF assay (Cepheid, Sunnyvale, CA) was positive for Mycobacterium tuberculosis (no rifampin resistance was detected). Urine AFB stain and urine NAAT were negative for TB; ultimately, the urine AFB culture was positive for TB. Despite a normal chest X-ray and reported lack of pulmonary symptoms, his sputum was also positive for TB by stain, NAAT, and culture. Antimicrobial susceptibility testing revealed no resistance to first-line agents. An immunoassay for human immunodeficiency virus (HIV) was nonreactive.
He was started on rifampin, isoniazid, pyrazinamide, and ethambutol. However, due to the development of hepatotoxicity 12 days into therapy without evidence of viral hepatitis, he was transitioned to ethambutol, levofloxacin, and intravenous amikacin. On treatment day 15, his sputum smears converted to negative. After resolution of his drug-induced liver injury on treatment day 26, amikacin was discontinued in favor of rifampin, and he was recalled to Cameroon soon thereafter on an all-oral, three-drug regimen.
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pmc-6192138-1
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This is a case of a 25-year-old Caucasian male who presented to the ED of St. Francis medical center on 12/2015 with visual hallucinations and symptoms of depression and anxiety, bilateral ear warmth, and swelling and eye redness. His behavioral symptoms have been going for six months prior to presentation. His initial brain MRI showed diffuse, patchy foci of increased FLAIR signal in the periventricular, deep, and subcortical white matter (). Right ear lobe biopsy was done and showed a mixed inflammatory infiltrate of the perichondrium composed of plasma cells, lymphocytes, histiocytes and neutrophils, and loss of the cartilage basophilia. GMS and AFB were negative for fungal and mycobacterial organisms. Those findings were consistent with RP.
CSF analysis on admission showed lymphocytosis (21 WBCs, 81% lymphocytes) and admission labs showed lymphocytosis and mildly elevated inflammatory markers ().
Based on his neurological presentation, his ear lobe biopsy finding, brain MRI findings [], and negative serologies, he was given a diagnosis of RP with meningoencephalitis.
He was started on IV 1-gram methylprednisolone for 7 days starting in 12/3/15 and then switched to oral prednisone 60 mg/day with a goal to taper off gradually.
The patient's clinical condition did not improve and repeat brain MRI did not show any significant interval change in white matter foci. As a result, the patient was given intravenous cyclophosphamide 1000 mg for total of 5 doses (first 3 doses 3 weeks apart, and another 2 doses 2 weeks apart) between 1/14/2016 and 3/17/2016.
Unfortunately, subsequent MRI after cyclophosphamide on 4/2016 showed progressive periventricular, mid, and also a component of superficial/juxtacortical white matter T2/FLAIR hyperintensity, the latter of which is more apparent within the frontal lobes. There has been further progression of hydrocephalus with diffuse ventricular enlargement ().
He was admitted in 5/2016 at SFMC for status epilepticus. Head CT done in the ED showed worsening hydrocephalus. VP shunt was placed and right frontal brain biopsy was done and showed infiltration of the dura and leptomeninges by a mixed chronic inflammatory infiltrate consisting of primarily histiocytes, but also lymphocytes and a few plasma cells. The brain parenchyma shows diffuse gliosis and scant perivascular infiltrates comprised of histiocytes and lymphocytes. No granulomas or vasculitis was identified. Special stains for fungal (GMS and PAS), acid fast (AFB), and bacterial (Gram) organisms are negative. Immunostains for HSV-1/2, CMV, and EBV are also negative. No parasitic organisms are seen on H&E or any of the special stains either. While these morphologic features are nonspecific, they could be consistent with CNS involvement by the patient's known RP. Repeat CSF analysis on the same admission showed 180 RBC, 468 nucleated cells (68% neutrophils, 17% monocytes, and 15% lymphocytes), and normal glucose and protein.
The patient was continued on oral prednisone treatment. A repeat MRI on 12/5/2016 did not show any improvement, so the decision was made to start rituximab and he got 2 doses in January 2017.
Subsequent brain MRI on 5/26/17 did not show any significant interval change in findings suggesting leptomeningitis/pachymeningitis, and foci of prolonged T2 values within the white matter ().
Currently the patient is in stable mute dementia status. He is alert. Language skills are very limited (up to one or two words mostly). He is relatively distractible. He can follow commands, but this is usually when demonstrated to him. He is currently on prednisone 15 mg/day which is being tapered off, and he is on methotrexate 25 mg/week since 4/2018 which was added as a steroid sparing agent to help taper down the prednisone dose.
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pmc-6192140-1
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A 50-year-old male presented with abdominal pain and unintentional weight loss over the course of one year. Physical exam and labs were normal. Computed Tomography (CT) of abdomen showed an 8.1 cm heterogeneous left adrenal mass, several bibasilar lung nodules, and several hypodense liver lesions concerning metastatic disease (). Positron Emission Tomography (PET) scan showed FDG avid left adrenal mass and mildly avid lung and liver lesions suggestive of metastatic disease. Pheochromocytoma was ruled out with negative urine metanephrines and catecholamines. There was no clinical evidence of Cushing's Syndrome. However, a nonfunctional adrenal cortical carcinoma (ACC) was the running diagnosis. Since the patient was not a surgical candidate and medical oncology was considering chemotherapy for ACC, EUS-FNA and CB of the left adrenal mass were performed. EUS revealed an irregular, hypoechoic mass, measuring at least 6.3 cm x 4.4 cm in maximal cross-sectional diameter (). Two hypoechoic round lesions in the left lobe of the liver were also identified but not sampled (). Pathology revealed a spindle cell neoplasm with extensive necrosis (). Tumor cells stained positive for desmin, cytokeratin Mak6, WT1, and S-100. Stains were negative for CD34 and chromogranin. Based on these findings, a diagnosis of primary leiomyosarcoma of the left adrenal gland was made. Adriamycin and olaratumab with palliative radiation for pain were then initiated as metastatic disease precluded surgery.
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pmc-6192156-1
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A 46-year-old African American man presented with complaints of progressive, bilateral, blurring (more in his right eye than his left) for the past 5 days. Our patient did not report a history of a prior similar episode. He denied the presence of any associated pain, trauma to his eye, redness of eye, headache, dizziness, weakness/paresthesia, changes in hearing, fever, chills, weight changes, recent travel, insect or tick bite, or sick contact. His past medical history was relevant for hepatitis B virus (HBV) diagnosed 5 years ago, and his past family history was noncontributory.
His vital signs on presentation revealed a blood pressure of 132/59 mmHg, heart rate of 72 beats/min, respiratory rate of 18/min, oxygen saturation of 100% at room air, and a temperature of 98.6 °F. On physical examination, our patient was in no apparent distress, awake, alert, and oriented to person, place, and time. He was icteric with palpable nontender hepatomegaly. Heart and lung examinations were unremarkable. A neurological examination revealed significantly reduced visual fields in both eyes with normal pupillary size and reaction, however, a funduscopic examination was unremarkable. His extraocular eye movements were intact without ptosis. Other neurological examinations were normal including motor, sensory, and cranial nerves.
Laboratory values from his first admission, second admission, and follow-up at 6 months were analyzed. On biochemistry, his electrolytes were within normal limits on all three occasions. Transaminase levels were markedly elevated on both the first and second admissions ranging from 500 to 1600 IU/L for aspartate aminotransferase (AST) and from 400 to 1500 IU/L for alanine aminotransferase (ALT). At the time of his 6-month follow-up, his AST and ALT levels were 51 and 87 IU/L respectively. Similarly, both his international normalized ratio (INR) and total bilirubin had improved to a normal range at follow-up. On complete blood count, his platelets remained stable on all three visits ranging from 127 to 210 kU/L. On both the first and second admissions, our patient was found to have positive hepatitis B envelope antigen, which was negative at the 6-month follow-up. Also, the hepatitis B virus deoxyribonucleic acid (DNA) load had markedly decreased from an average of 150 million IU/mL to 5000 IU/mL. Otherwise, his hepatitis B core immunoglobulin M (IgM), surface antibody and antigen, and hepatitis B virus envelope antibody remained unchanged.
A presumptive diagnosis of optic neuritis was made and a differential diagnosis included multiple sclerosis and infectious etiology. The laboratory data are summarized above. Other serology test results, including for hepatitis C virus (HCV), hepatitis A virus (HAV), human immunodeficiency virus (HIV), syphilis, babesia and Lyme disease, were negative. A magnetic resonance imaging scan (MRI), with and without gadolinium, of his brain, orbits, neck, and spine were unremarkable. A lumbar puncture was performed considering multiple sclerosis in the differential diagnosis; cerebrospinal fluid (CSF) cytology was negative for infection and malignant cells, but showed few mature lymphocytes admixed with monocytes. CSF isoelectric focusing/immunofixation demonstrated identical bands in the CSF, consistent with a systemic, no intrathecal immune reaction, and was considered to be a negative result for oligoclonal bands. His albumin CSF level was 25 mg/dL, albumin index 6.3, and CSF IgG/albumin ratio 0.26. A diagnosis of retrobulbar optic neuritis was made in association with an HBV flare.
During the first admission, our patient was started on prednisone 1 mg/kg/daily for 14 days and entecavir 1 mg/daily long-term therapy.
After few days of steroids, his blurring of vision completely resolved. He was discharged home with follow-up appointments as an outpatient. After 12 months, he presented with similar complaints after stopping his antiviral medication for 2 months. A presumptive diagnosis of optic neuritis associated with acute on chronic HBV was made. Because he had a flare of his viral hepatitis (with an AST level of 1558 IU/L and ALT level of 1488 IU/L), steroid therapy was avoided, and he was treated with entecavir alone. Our patient’s visual acuity improved after 5 days of entecavir (1 mg once daily) therapy. His abdominal tenderness resolved, liver enzymes improved, and his INR returned to baseline level.
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pmc-6192168-1
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An 18-year-old man with a past medical history significant for an osteochondroma of the right forearm presented with a three-month history of a slowly enlarging right testicle. At the time of his initial presentation, the testicle had reached 9–10 cm in diameter. The patient was asymptomatic aside from the enlarged testicle without any constitutional symptoms. Tumor markers, including alpha fetoprotein and beta human chorionic gonadotropin, were negative. Family history was significant for a maternal grandmother with uterine and colon cancer both diagnosed in her 60s, a paternal grandfather diagnosed with prostate cancer in his 60s, and a maternal great grandfather diagnosed with leukemia in his 30s.
A unilateral orchiectomy was performed. Pathology was consistent with mature teratoma (90%) and PNET (10%). Chest and abdominal CT scan revealed multiple retroperitoneal lymph nodes matted into a mass. Retroperitoneal lymph node dissection (RPLND) was performed revealing mature and immature teratoma with 60–70% transformation to PNET. This positive lymph node spread prompted second opinion review of the pathology. Second opinion pathologic evaluation of the primary tumor revealed nonseminomatous mixed germ cell tumor composed of mature and immature teratoma (95%, of which 30–50% was PNET), yolk sac tumor (3%), and embryonal carcinoma (2%). Due to the PNET component, 18F-FDG-PET (PET) imaging was obtained which revealed a 1 cm PET avid left lower lobe lung nodule with a standard uptake value (SUV) of 2.8. A multidisciplinary team discussed treatment and planned for surgical resection of the lung nodule following initiation of therapy. There was concern that the patient was progressing when the FDG-PET avid nodule was discovered, and there had been considerable delay in confirming the diagnosis. As such, it was decided to proceed with chemotherapy and explore the pathology of the nodule if the patient did not experience adequate treatment response. Given the unusual nature of his case and the presence of several family members with a history of cancer, the patient was offered TP53 genetic testing but declined.
Combination chemotherapy was initiated with an alternating regimen that included cycles of vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide given in compressed two-week cycles. The patient tolerated chemotherapy well without any major toxicity aside from intermittent mild myelosuppression.
Reevaluation of the PET avid lung nodule occurred prior to cycle 5 and showed persistent avidity with an SUV of 2.92. A wedge resection of the left lower lung lobe nodule was completed following cycle 9 of chemotherapy. Pathology of this nodule revealed mature teratoma (40%), osteosarcoma (30%), and adenocarcinoma (30%) components ().
Treatment was subsequently amended to an osteosarcoma-based treatment regimen that contained four cycles of cisplatin with doxorubicin again alternating with 3 cycles of ifosfamide and etoposide. Total cumulative dose included doxorubicin 600 mg/m2, cisplatin 360 mg/m2, ifosfamide 54 g/m2, etoposide 3 g/m2, and cyclophosphamide 6 g/m2. He received dexrazoxane for cardioprotection prior to each doxorubicin infusion for a total cumulative dose of 6 g/m2. The patient's end of therapy evaluation was negative for any evidence of disease, and he is alive with no evidence of disease after 18 months.
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pmc-6192182-1
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We report a case of 38-year-old Greek woman who presented to our Emergency Department complaining of abdominal pain during the last week without any other symptoms. Her clinical history was clear and she had not noticed the occurrence of the same symptoms before. A clinical examination revealed only focal tenderness in the left part of her abdomen. Laboratory results were within normal limits. During an ultrasound examination of her abdomen, an anechoic lesion in her upper left abdomen was revealed. In a further investigation with computed tomography (CT), a well-defined hypodense cystic 7.08 × 6.05 cm mass with mild enhancement was noted (Fig. ). Surgical approach was decided after a thorough examination and our patient gave her consent for surgery. A cystic lesion sized 7.08 × 6.05 cm appeared between the layers of small bowel mesentery (Fig. ). The cystic lesion was excised within healthy borders and sent for further pathologic examination (Fig. ). On macroscopic examination, the cyst sized 7.08 × 6.05 cm was unilocular and contained a white, milk-like viscous fluid (chylous), which was drained out by incision. Histopathological investigation showed a thick fibrous wall, pervaded by chronic inflammatory cells (lymphocytes and plasma cells) and lymphoid aggregates. Variously sized vessels could also be observed while immunohistochemically CD31 (platelet endothelial cell adhesion molecule) was positive (Fig. ). CD31 is used primarily to demonstrate the presence of endothelial cells and can help to evaluate the degree of tumor angiogenesis. A definitive inner epithelial lining was not found. On the inner surface, multiple aggregates of foamy macrophages as well as focal foreign-body giant cells were present. (Fig. ) The thickness of the wall varied trivially with small parts of mature fat tissue toward the outer surface, indicating the mesentery. The findings were found to be most consistent with a simple lymphatic (chylous) cyst of the mesentery in combination with features of a non-pancreatic pseudocyst. Her postoperative course was uneventful and patient feeding was started on the second postoperative day. She was discharged on the fifth postoperative day while she had a low-grade fever. A 6-month follow-up with abdomen ultrasound and 1-year CT imaging showed no signs of recurrence.
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pmc-6192270-1
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The patient was a 67-year-old man who presented with dysuria. Computed tomography (CT) examination of the upper abdomen revealed multiple swollen retroperitoneal and pelvic lymph nodes and abnormal bone density on January 5th 2015. Positron Emission Tomography-CT (PET-CT) revealed hypermetabolic lesions in the left lobe of the prostate, and multiple bone sites, as well as enlarged lymph nodes of the left neck, supraclavicular region, retroperitoneal, bilateral iliac blood vessels and pelvic left side wall, which were diagnosed as malignant metastasis on February 5th 2015. A prostate biopsy was performed on February 28th 2015, and histologic assessment showed conventional adenocarcinoma with Gleason score 4 + 3 = 7, while serum TPSA level was >100 ng/mL. The clinical course of the patient was summarized in Fig. .
The patient started the treatment with bicalutamide tablets, zoladex and zoledronate on February 28th 2015. His TPSA level dropped to 13 ng/mL after two months of treatment, and he continued on the therapy. However, recurrent disease developed on July 9th 2015, marked by elevated TPSA up to 60 ng/mL. The patient was then switched to the treatment with flutamide and zoledronate. On October 10th 2015, due to persistent increase in TPSA level, the patient was further treated with abiraterone. On February 5th 2016, emission CT showed progression with bone metastases, with TPSA level rising to 150 ng/mL. The patient then started six cycles of systemic chemotherapy with docetaxel and metacortandracin, during which time his TPSA level continued to rise. One month after finishing the systemic chemotherapy, his TPSA level reached 492.3 ng/mL. The patient then received enzalutamide, but by August 22nd 2016, the TPSA level had risen to 644.3 ng/mL.
Considering the poor responses to all currently available therapies, we performed genetic testing on patient’s circulating tumor DNA (ctDNA) from blood using next-generation sequencing (NGS) targeting over 400 cancer-relevant genes. The assay was done using a commercial test. Genomic DNA from the whole blood sample was used as germline control. We detected several genomic alterations known to be associated with prostate cancer; specifically, we identified PIK3CA-Q546K activated mutation with a mutant allele frequency (MAF) of 17%, a TP53-DISCIFP1 fusion (MAF: 12%), 4.1 folds of relative copy number gain of the AR gene, as well as germline BRCA2-G1761X mutation. As a result, the patient started treatment with everolimus, a mTOR inhibitor, for his high MAF of PIK3CA-Q546K mutation. Despite this however, serum TPSA continued to increase slowly 798.9 ng/mL to 1379 ng/mL. On October 27th 2016, CT scan showed progression of multiple lymph nodes metastases, double pleural effusion and appearance of new liver metastases (Fig. ). The patient also developed a fever, shortness of breath and lethargy followed by unconsciousness. The patient was transferred to the intensive care unit (ICU) and underwent transfusion, respirator assisted ventilation and tracheotomy.
Due to prior detection of the BRCA2 G1761X germline mutation and poor physical condition, the patient started on olaparib treatment, 400 mg twice daily by nasal feeding tube, on November 1st 2016; the patient tolerated the dose and his symptoms significantly relieved. On December 26th 2016, CT assessment indicated a partial response (PR) of liver metastases to olaparib (Fig. ). Furthermore, TPSA level was reduced from 1379 ng/mL to 208 ng/mL. Following resolution of fever, shortness of breath, lethargy and unconsciousness, the patient was transferred out of the ICU. On January 22nd 2017, the patient’s blood sample was obtained for ctDNA testing by NGS, which showed that the tumor specific mutations identified before the treatment had significantly decreased (PIK3CA-Q546K, 0.4%; TP53-DISCIFP1 fusion, 0.1%; undetectable copy number gain of AR). After four months of the therapy, his TPSA level continued to fall to 30.65 ng/mL. However, unfortunately, the patient’s disease progressed again after six-month of the treatment, and his ctDNA testing showed that all the previous detected tumor specific mutations elevated to an even higher level compared to pretreatment (PIK3CA-Q546K, 19.9%; TP53-DISCIFP1 fusion, 29.1%; 4.1 folds of relative copy number gain of AR), as well as a newly emerged RB1 single copy number loss. In addition, some other somatic genomic alterations had been found in the third test (Table ).
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pmc-6192278-1
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A 36-year-old Brazilian male patient was admitted to the hospital with a palpable lump in his right breast, located at the junction of the upper quadrants of the right breast (Fig. ). On physical examination, the lesion appeared firm with irregular margins. Axillary lymphadenopathy was negative and there were no palpable supraclavicular nodes. On breast imaging, ultrasonography showed a hypoechoic mass with partially defined contours measuring 4.0 × 3.0 cm, located at the upper region of the right pectoralis major muscle at the 12 o’clock position with muscle infiltration (Fig. ). Histological examination of core biopsy samples revealed a malignant tumor. Preoperative exams, such as X-rays and chest CT scan, abdominal US did not show any signs of disease. Radical mastectomy was then performed, due to pectoralis major muscle infiltration, consisting in removal of the breast along with the major and minor pectoralis muscles. Biopsy of the sentinel lymph node was performed. Gross examination revealed a solid tumor measuring 3.7 × 3.5 cm with a yellowish-tan cut surface and local foci of hemorrhage. Histopathology showed intravascular papillary proliferation of endothelial cells, spindle cell areas and necrosis, atypia and prominent mitotic figures, consistent with the diagnosis of high-grade angiosarcoma with areas of infiltration of the pectoralis major muscle (HE staining, magnification of 400×) (Fig. ). Histopathology also demonstrated a surgical specimen with clear margins, absence of angiolymphatic and perineural invasion, in addition to sentinel lymph node free of metastasis. Immunohistochemical study revealed a tumor positive for CD31 marker (Fig. ), confirming the vascular nature of the tumor. At the two-week follow-up of the surgical procedure, adequate wound healing was observed, without any evidence of the disease. The patient was transferred to the clinical oncology department, where he presented with severe headache and seizures after the second cycle of adjuvant chemotherapy with paclitaxel. Magnetic resonance imaging of the brain was ordered, revealing a right frontal parasagittal lesion, measuring 1.3 × 1.1 cm with a hemorrhagic component and perilesional edema, suggestive of brain metastasis. The disease progressed rapidly, culminating in the patient’s death at 20 days after the onset of neurological symptoms.
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pmc-6192282-1
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A 32-year-old white woman presented to our clinic in 2009 complaining about floaters in her right eye and severely reduced visual acuity in her left eye. Her visual acuity was 20/20 in her right eye and hand motion perception in her left eye. A fundus examination revealed vitreous hemorrhage in her right eye and retinal detachment in her left eye. She was admitted and emergency surgery was performed.
There was no previous ocular trauma or history of other eye diseases/eye surgery. There was no family history of eye diseases.
Scatter laser photocoagulation was performed in her right eye and at a follow-up visit in July 2009 a fluorescein angiography was performed. This showed neovascularization of the optic disc, and non-perfusion in the peripheral retina with peripheral neovascularization and central neovascularization that involved the temporal part of the macula. The best-corrected visual acuity in her right eye was 20/20; intraocular pressure was 12 mmHg (Goldmann applanation tonometry). Perivasculitis with periphlebitis and vitreous hemorrhage was also noted. An optical coherence tomography (Heidelberg Spectralis®) scan showed atrophy of the internal retinal layers corresponding to the area of non-perfusion and a thickening of the internal limiting membrane.
Laser treatment was performed and 1 month later neovascularization of the optic disc decreased but residual perivasculitis was noted. An optical coherence tomography scan was stable except for further thickening of internal limiting membrane and incipient epiretinal membrane formation. Other laboratory workups including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), angiotensin-converting enzyme (ACE), interleukin-2 (IL-2) receptor, Treponema pallidum hemagglutination assay (TPHA), partial thromboplastin time (PTT), Venereal Disease Research Laboratory (VDRL), and interferon-gamma release assay (QuantiFERON-TB Gold) revealed no significant abnormalities. Thorax radiography revealed no suspicious lesions indicating sarcoidosis or tuberculosis. A further review of her systems was unremarkable. There were no accompanying systemic signs and symptoms except lower back pain and marginally reduced hip mobility that was diagnosed as human leukocyte antigen-B27 (HLAB27) positive sacroiliitis.
In 2010 our patient became pregnant and her disease course was stable for the duration of the pregnancy with no additional treatment needed.
At 25 months from baseline (1 month after childbirth) our patient presented with recurrence of vitreous hemorrhage and worsening of visual acuity (20/40). On fluorescein angiography there was severe perivasculitis, optic disc neovascularization, and increased area of non-perfusion. More scatter laser photocoagulation was performed and orally administered prednisone 1 mg/kg with a slow taper was started. However, stability in angiography and clinical findings was not achieved. At 28 months from baseline, she was started on methotrexate 20 mg/week and prednisone 10 mg/day. Because of hepatotoxicity, methotrexate was tapered and at 40 months from baseline azathioprine 100 mg and mycophenolate mofetil 1.5 mg was prescribed. Despite aggressive systemic therapy, the disease course was relentless. At 43 months from baseline, enlargement of non-perfusion area was noted and intense perivasculitis was noted on fluorescein angiography. On an optical coherence tomography scan loss of internal retinal layers was noted that involved the temporal half of the fovea. An epiretinal membrane with slight papillomacular traction was observed. At 44 months from baseline a dexamethasone sustained-release implant (Ozurdex®, Allergan; Bucharest, Romania) was injected. This halted the disease, with a best-corrected visual acuity of 20/20 progression and since then ten steroid implants have been used. We recommended injection every 4 months but because of the financial burden for our patient (no reimbursement for Ozurdex®) we injected based on worsening of angiogram, optical coherence tomography, and/or recurrent vitreous hemorrhage.
She stopped mycophenolate mofetil at 74 months from baseline after a slow taper and azathioprine at 75 months from baseline.
She underwent uneventful cataract surgery at 67 months from baseline for her right eye and at 48 months from baseline for her left eye preceded by vitrectomy for retinal detachment in 2009 and second vitrectomy with silicone oil injection for proliferative vitreoretinopathy at 85 months from baseline. In November 2016, fluorescein angiography was stable with minimal vasculitis, no active neovascularization, and no progression of non-perfused areas for her right eye. The last Ozurdex® was implanted 109 months from baseline. Although there are studies showing intraocular pressure increase after Ozurdex® [], in our case there was no need for intraocular pressure-lowering medication as throughout the follow-up period pressures were between 10 mmHg and 18 mmHg. Additional files provide comparison between fluorescein angiography before Ozurdex implantation and after the last implant was used (Additional file ) and optical coherence tomographies showing progression from baseline to the last follow-up visit (Additional file ). Widefield imaging and composite fundus photography can be observed in Additional file . Additional file provides an overview of the therapeutic approaches (case report timeline.
Follow-up examinations were aimed at picking up early signs of disease progression and we gave timely injections of Ozurdex® in order to preserve a functional retina taking into account the financial burden for our patient. In our case the systemic therapy was much less effective than the intravitreal sustained-release dexamethasone implant for reducing recurrences and halting disease progression. Currently our patient is completely functional at work with 20/20 visual acuity for her right eye and light perception for her left eye. Despite the reduced visual field, according to her statements, she is able to perform all daily activities with ease.
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pmc-6192299-1
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We report the case of a 29-year-old female with a past medical history of smoking (5-pack-years) and a spontaneous pneumothorax four years earlier. The aforementioned pneumothorax was complicated by continuous re-expansion of the air chamber, resolving only after atypical basal segment lung resection and pleurodesis by video-assisted thoracotomy. The patient had no family history of spontaneous pneumothorax, cancer or consanguinity.
On April of 2014 on a routine gynaecological consultation a pelvic ultrasonography revealed multiple and bilateral hypoechogenic renal masses. The patient was immediately referred to urology care. The patient underwent percutaneous ultrasound-guided kidney biopsy. Histology report identified cells suggestive of carcinoma. On computer tomography multiple masses were present on both kidneys and bilateral nephrectomy was scheduled. Two days after surgery the patient was started on a regular haemodialysis program.
The pathology report of nephrectomised samples revealed the right kidney had nine intra-renal tumoural masses, not invading the capsule and corresponding to renal cell carcinoma of chromophobe cell type. The left kidney had nineteen intra-renal masses with the same histology, without capsular involvement. The tumour was staged according to TMN classification system, 7th edition, as T1b Nx Mx, with no residual tumour. Since surgical margins were negative and there were no signs of distant metastatic disease, the patient was not proposed for adjuvant chemotherapy.
While on regular haemodialysis, multiple small whitish papules were noticed predominantly on the head and neck. These papules had been slowly appearing after the age of 20. Skin biopsy confirmed hair follicle benign tumours of trichodiscoma type [Fig. ].
Considering the patient past medical history and the skin lesions, Birt-Hogg-Dubé (BHD) syndrome was considered. The hallmark features of this genodermatosis are benign skin tumours of fibrofolliculoma, trichodiscoma or acrochordon type [, , ]. This syndrome is also characterized by a strong link to renal cancer and spontaneous pneumothoraxes, with some authors reporting a 7-fold increased risk for developing renal tumours and 50-fold for developing spontaneous pneumothoraxes compared to normal population []. The renal tumours are multifocal or bilateral in the majority of patients with BHD and the most typical histological types are pure chromophobe, oncocytomas and hybrid chromophobe renal cell carcinoma [, , ]. According to the European Consortium guidelines, this patient had 1 major criteria and 2 minor criteria for BHD syndrome [].
Genetic analysis confirmed an heterozygote mutation on FLCN gene, in exon 6 (C.573_574delinsT). The family was screened for the mutation and it was found on 3 other family members (father, sister, first degree cousin), which are now on surveillance program.
The patient has been on dialysis for 2 years now. Though there has not been any report of a patient with BHD being transplanted, risks and benefits for this patient were weighted. She has been considered apt by the transplant team and is currently waitlisted for cadaveric renal transplantation.
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pmc-6192350-1
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A 51-year-old Caucasian woman presented to our out-patients’ clinic with a 2-week history of worsening abdominal pain in her left upper quadrant, exacerbated by abdominal flexion and extension maneuvers. She described symptoms as intermittent, and accompanied by loss of appetite, nausea, and having a “feculent” taste in her mouth. Her previous medical history was notable for an elevated body mass index (BMI) of 41 kg/m2, and in the year 2000 for laparoscopic adjustable gastric band (LAGB) implantation. She experienced weight loss of 30 kg after her original procedure, although 3 years later a partial perforation of the band into her stomach developed (confirmed endoscopically). Over the subsequent years, she required serial endoscopic follow-ups until 2005 when the band was covered by the gastric mucosa only on one third of its surface. From then on and for unknown reasons the endoscopic follow-up ceased. She remained asymptomatic and regained weight up to a BMI of 36.3 kg/m2 until her current presentation.
A clinical examination revealed left-sided abdominal tenderness without signs of abdominal guarding. The blood results were unremarkable, except white blood cells (WBC) with 11.3 G/l. A plain abdominal radiograph showed signs of small bowel obstruction (Fig. ); and abdominal computed tomography scanning revealed intraluminal migration of the gastric band into the distal jejunum – still connected to the subcutaneous reservoir – folding the intestine on the catheter like a hand organ instrument (Fig. ).
After an unsuccessful attempt to remove the band endoscopically, our patient underwent a diagnostic laparoscopy, which showed that the gastric band was impacted in the distal jejunum causing obstruction. An enterotomy was performed via umbilical mini-laparotomy, and the partially digested silicon band was retrieved (Fig. ). The involved jejunal segment was resected due to its conglomerate formation with possible stenosis, followed by an end-to-end anastomosis. The operation was completed by removal of the port with the remaining catheter through the original port-site incision. The catheter entrance into the stomach was left untouched, and our patient’s recovery was uneventful. She explicitly did not want a conversion about an alternative bariatric surgery and refused further follow-ups.
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pmc-6192393-1
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Since the clinical history of this patient, a 45-year-old woman at death, is already available elsewhere in Japanese (Nakazato et al., ), this report only describes the outline of it. At the age of 38, she manifested with difficulty in walking. A neurological examination 6 months after the onset disclosed spastic gait coupled with spasticity and pyramidal signs in both legs. A clinical diagnosis of “familial spastic paraparesis” was made. Two years after the onset, she became unable to walk. Soon dysarthria, emotional incontinence, and tremor of the tongue and fingers appeared. Eventually, she became severely demented and died of aspiration pneumonia 6 years after the onset.
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pmc-6192393-2
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Since the clinical history of this patient, a 56-year-old woman at death is already available elsewhere in Japanese (Isshiki et al., ), this report only describes the outline of it. When she was 5 years old, she was affected with poliomyelitis. Since then her right hand remained paralytic, but there was no problem in her daily life. At the age of 44, she manifested with difficulty in walking, and 4 months later, she became almost unable to walk. Soon dysarthria became evident. About 2 years after the onset, a clinical diagnosis of “familial spastic paraparesis” was made, and thereafter, she became bedridden. Then, she was admitted to a psychiatric hospital for the management of severe emotional disturbance. The pyramidal signs in the upper and lower limbs, chorea-like movement in the left upper limb, apathy, and dementia followed, and she died at the age of 56, 12 years after the onset.
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pmc-6192393-3
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This patient, a 49-year-old man at death, is the son of Case 2. When he was 47 years old, he suffered from hemorrhoids and had them surgically removed. But after the operation, he repeatedly complained of anal pain and kept on consulting several hospitals. Soon, the family members found his way of walking somewhat clumsy. About 1 year later, he presented with tremor in his fingers. About 2 years after the onset, his stereotyped behavior and speech became more apparent; he walked around the same place at the same time each day; and he dropped in at the same store and bought the same foods (bread and cola). There was an episode where he complained of lucency of his teeth, and he consulted a dentist three days in a row. He began to make comments like “I have been deceived,” or “I have been robbed.” He became restless and easily agitated, which culminated in an attempted strangulation of his wife. He was hospitalized and remained conscious but did not utter any words. There was a tremor in the upper limbs, and there was myoclonus, which disappeared later, in the lower limbs. In all extremities, deep tendon reflexes were exaggerated but there was no paresis. There were no signs of sensory and cerebellar impairment. During the hospitalization, he relentlessly complained of anal pain and repeatedly ate the same foods (hamburgers and cola). The brain magnetic resonance imaging (MRI) showed mild frontotemporal atrophy, but did not disclose any signal abnormalities on diffusion MRI. The complaint of anal pain was so tenacious that oral morphine was introduced. But he unexpectedly passed away due to paralytic intestinal obstruction leading to septic shock. The whole clinical course was about 2 years (2 years and 3 months). The P105L point mutation of PRNP coupled with codon 129 polymorphism (Val/Met), which is identical to that of Case 1 and Case 2 (Kitamoto, Amano, et al., ), was detected by a genetic analysis using blood samples. An autopsy limited to the brain was performed.
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pmc-6193093-1
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A 6 week-old African-American female was born to nonconsanguineous parents. The G2P1 mother had a surgically removed pituitary prolactinoma prior to her pregnancy, which was complicated by gestational diabetes and hypertension.
The infant was born via spontaneous, vaginal delivery at 34 weeks and 2 days gestation. Birth weight was 2,091 grams (28%ile), length was 42.5 cm (12%ile), head circumference was 30 cm (30%ile), and Apgar scores were 6 and 8 at 1 and 5 min, respectively. Although intubated shortly after birth due to weak respiratory effort, she was extubated soon after without complications. Her physical exam was significant for heart sounds on the right side of her chest, and an echocardiogram demonstrated dextrocardia and a small atrial septal defect. The rest of her physical exam showed a well-appearing newborn, with normal vital signs, moist mucous membranes, appropriate capillary refill time, and normal infantile genitalia. Ultrasonography showed situs inversus and a duplicated right renal collecting system. Microarray results were consistent with chromosome 1q21.1 deletion syndrome.
Hyponatremia (serum sodium 128 mmol/L) was identified shortly after birth, although other electrolytes and kidney function were normal. Serum osmolality was low at 270 mOsm/kg (normal 275–295), urine osmolality was inappropriately elevated at 455 mOsm/kg, and urine sodium was also relatively high at 123 mEq/L. Plasma AVP level was significantly elevated at 32.7 pg/mL (normal 1–11). These findings were consistent with a diagnosis of SIADH.
Further evaluation showed a normal plasma aldosterone at 6 ng/dl (normal 1–197) and a normal 17-hydroxyprogesterone level on newborn screen. A random cortisol level was low at 3 mcg/dl (normal 5–25), but ACTH stimulation test was normal with a peak cortisol response of 48 mcg/dl. Thyroid function test showed a normal free T4 level of 1.5 ng/dl (normal 0.76–1.46) and a normal TSH level at 2.9 mIU/L (normal 0.7–11.0). Liver studies, triglycerides, and serum albumin levels were also normal.
Brain magnetic resonance imaging (MRI) revealed a markedly diminutive posterior pituitary hyperintensity on T1-weighted images (Figure ), a malformed sella turcica with otherwise normal adenohypophysis, posterior/inferior hypothalamic malformation with hypoplastic and incompletely separated mammillary bodies, mild vermian hypoplasia, mild cerebral white matter volume loss or hypoplasia, and mild microencephaly.
Figure demonstrates the serum sodium levels and weight of the infant as a function of time throughout the course of the infant's care. Sodium supplementation of up to 12 mEq/kg/day and fluid restriction resulted in minimal improvement in the serum sodium level, and actually led to mild hypertension. Hyponatremia not associated with hyperkalemia or metabolic acidosis renders isolated mineralocorticoid deficiency a less probable diagnosis; however, due to the persistent hyponatremia, a two-day trial of fludrocortisone was attempted but failed to improve the infant's serum sodium levels. Furosemide 2 mg/kg/day was added at 7 weeks of age with little effect. Tolvaptan (crushed and mixed with formula) was started at 0.05 mg/kg/day at 7 weeks of age, which resulted in normalization of her serum sodium levels. Sodium supplementation was subsequently weaned over the next few days, which resulted in blood pressure normalization. The daily fluid intake of the infant was successfully increased to provide the required caloric intake without development of hyponatremia.
The patient was discharged normotensive from our center at the age of 8 weeks with a normal serum sodium level of 136 mmol/L. Her discharge prescriptions included 4 mg of furosemide twice daily (2.4 mg/kg/day), 4 mEq of sodium chloride three times daily (3.75 mEq/kg/day), and 0.3 mg of tolvaptan once daily (0.09 mg/kg/day). She was discharged on a fluid restriction of 137 mL/kg/day of 28 kcal/oz of fortified formula to support her growth as a premature infant.
As the patient grew and gained weight, her daily formula intake was increased to maintain adequate caloric intake. Her tolvaptan dose has been incrementally increased with the increased fluid volume to prevent hyponatremia. Her weight and height have continued to track along the 1st percentile. Her head circumference is tracking below the 1st percentile.
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pmc-6193294-1
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The clinical story of this 62 year old woman started in 2007 with lower back pain, lumbar muscular contractures and back rigidity. After being examined by an orthopaedic surgeon, she was diagnosed with congenital scoliosis. A lumbar interbody fusion was subsequently performed with no significant impact on the symptoms.
Between 2007 and 2014, she presented multiple episodes of lower limb myoclonus. Episodes were often associated with hyperthermia. A diagnosis of spinal myoclonus was suggested and a treatment with clonazepam began.
In 2014, she presented with lower limb myoclonus, confusion, hyperthermia and acute respiratory failure. She was admitted to the intensive care unit (ICU). Differential diagnoses at the time included NMS versus meningoencephalitis. Nevertheless, no past history of neuroleptic use was identified and multiple attempts of lumbar puncture were unsuccessful. Large spectrum antibiotics were administered with favourable clinical evolution.
She finally presented in our hospital in our emergency department (ED) in January 2017 for recurrent myoclonus and a sudden onset of bilateral leg weakness in the context of an influenza infection. Upon arrival at the ED, moderate hypotension and fever (39.4 °C) were observed. Neurological examination showed bradyphrenia, however she followed one-step commands. There was a motor deficit of the lower extremities scored 4 on the Medical Research Council scale (MRC) [], diminished and symmetrical knee and ankle jerks, myoclonus and rigidity in the lower limbs. Initial laboratory tests showed normal white cell count with moderately increased C reactive protein (CRP; 39 mg/l, normal: < 5 mg/l). Creatine kinase (CPK) was elevated at 52144 U/L (normal: 10–170 UI/l) with an acute renal insufficiency (clearance of 14 ml/min). Clonazepam doses were increased from 1 mg to 2 mg three times daily and antibioc therapy with amoxicillin/clavulanic acid was empirically started.
The day after admission in the neurology ward alteration of the level of consciousness, persistent hypotension and respiratory distress were observed and the patient was subsequently admitted to ICU. In the following days, there was a progressive deterioration of the motor function in the lower limbs until paraplegia was reached while lower limb rigidity and myoclonus persisted. Patient contact was lost with respiratory failure, necessitating invasive mechanical ventilation during one week.
Brain and spinal magnetic resonance imaging (MRI) revealed a pituitary adenoma, cervical osteoarthritis and thoraco-lumbar discopathy without stenosis. EMG showed continuous rhythmic motor unit activity within the axial muscles. CPK continued to rise in the following days to peak of 74,410 U/L. CSF analysis was normal, polymerase chain reaction (PCR) for herpes simplex virus 1 (HSV1), HSV 2 and enterovirus were negative (Table ).
In doubt, anti-epileptic treatment with levetiracetam (2 g twice daily) was started. Nonetheless, a consecutive twenty-four-hour electroencephalogram (EEG) demonstrated numerous muscular artefacts but no epileptic activity (Table ).
An extensive blood investigation (Table ) was performed including: human immunodeficiency virus (HIV), anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), Anti-double-stranded DNA antibody, antibody to extractable nuclear antigens, anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA), Anti-actin antibody (AAA), Anti-glomerular basement membrane antibody (anti-GBM Ab), paraneoplastic syndromes, complement C3 and C4, mycoplasma, influenza, enterovirus, adenovirus, borrelia burgdorferi, cytomegalovirus, cardiolipine antibody, lupus anticoagulant, thyroid function and paraneoplastic neurological antibodies (anti-Amphiphysin, anti-Hu, anti-Yo, anti-CV2, anti-Ri, anti-Ma2/Ta, anti-Sox1 and anti-Titin). All test results were either normal or negative. However, our patient was tested strongly positive for the antibodies to GAD (95; normal values 0–5). Together with the clinical presentation this ultimately led to the diagnosis of PERM syndrome.
Initial treatment was therefore started with gamma-globulins (0.4 g/kg/day) during 5 days with poor results. Concomitant corticotherapy was started with IV hydrocortisone (50 mg, three times daily) for 10 days, which was then continued orally. The treatment was continued with five sessions of plasma exchange (2 L). Recovery of her consciousness followed within days and myoclonus ceased. She was extubated one week after the end of plasma exchange sessions. Total duration of the ICU stay accounted 33 days. The patient was then transferred to the neurology ward where she recovered progressively with respect to motor function; she was able to walk with a walker when discharged to a rehabilitation centre.
While still in rehabilitation, our patient had a short relapse of the myoclonus in March 2017, only after she was already shortened on her corticosteroids and anti-epileptics. Decision was made to keep her on a regimen of levetiracetam 2 g twice a day and hydrocortisone 20 mg twice daily. She left the rehabilitation centre in May 2017 with a favourable evolution despite persistent mild lower proximal limb weakness (scored 4 on the MRC scale) and gait ataxia.
In August 2017, seven months after admission, she had no relapse of the myoclonus nor the rigidity and was able to walk without assistance. Hydrocortisone was reduced to 10 mg twice daily.
In October, she was again admitted for intermittent episodes of myoclonus (less than 60 min). Myoclonus rapidly disappeared after treatment with IV methylprednisolone (1 g) for three consecutive days. Steroids dose were increased again to 20 mg twice daily. She is now followed monthly at the outpatient clinic and levetiracetam treatment has been progressively stopped while hydrocortisone is maintained at the same dose.
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pmc-6193295-1
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A 31-year-old woman was admitted to our hospital with the chief complaints of anhydrosis on the left upper limb, ipsilateral face, and miosis. These symptoms developed without apparent causes and in the absence of other problems, such as ptosis, enophthalmus, fever, chest pain, breathlessness, cough, expectoration, nausea, or vomiting. Contrast-enhanced computed tomography of the chest revealed a 6.1 × 5.6 × 5.5-cm, well-circumscribed soft tissue mass in the left posterior mediastinum (Fig. ). In addition, adjacent intervertebral foramen of thoracic vertebra became larger, and bone destruction of the left second rib can also be seen. Particularly, there was no enlarged lymph node within the mediastinum.
A left posterolateral thoracotomy through the fifth intercostal space was performed. During the surgery, it was found that the mass which was approximately 6 × 5 × 5 cm in size arose from the cortex of the second rib and was hard in consistency. Ossification could also be seen within the tumor. We resected the tumor completely and removed partial sclerotin on the surface of the second rib. Histopathologic examination confirmed the diagnosis of chondroma (Fig. ). Her postoperative course was uneventful. She was discharged without any complication in 12 days after surgery. Follow-up high-resolution computed tomography scans have not detected recurrence 42 months after surgery.
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pmc-6193307-1
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A 60-year-old Moroccan man, without a personal history of diabetes or chronic disease, nor any special chirurgical or psychosocial background or toxic habits, and with a familial history of diabetes. He presented with a 3-year history of a progressively asymptomatic nodule of his right index finger. The tumor was voluminous, which motivated the patient to consult in our department. The clinical examination revealed a 2.5 cm purplish painless soft tumor, covered with yellowish and hemorrhagic crusts, involving the first phalanx of the right index finger. This tumor was compressing the nail plate (Fig. ). Our patient did not report any intense pain, cold sensitivity or severe tenderness to palpation of the tumor of his right index finger, and no previous trauma history. A neurologic examination showed no signs of paresthesia or hypoesthesia, and muscular and neurological function was preserved. The dermoscopic examination had revealed polymorphic vessels, in a rainbow pattern with melliciric and hemorrhagic crusts (Fig. ). A general examination showed no other abnormality. The differential diagnosis included angifibroma, pyogenic, granuloma-like Kaposi sarcoma, epidermized pyogenic granuloma, superficial acral fibromyxoma and glomus tumor. No bony lesions were identified on radiographic studies (Fig. ) and magnetic resonance imaging (MRI) was suggestive of glomus tumor by individualizing a 26 × 16 mm low tissue mass signal intensity on T1, marked hyperintensity on T2, and enhancement on T1 after gadolinium injection (Fig. ).
Surgical excision was performed. The approach was direct, respecting the principles of cutaneous incisions and avoiding nerve fiber pathways. The mass was well circumscribed and removed (Fig. ). Histopathologic examination with hematoxylin-eosin stain, demonstrated round to ovoid cells, lacking nuclear atypia and featuring scant, eosinophilic cytoplasm (Fig. ). The cell clusters were traversed by narrow vascular clefts lined with regular flattened endothelial cells (Fig. ). Mitotic activity was absent. Immunohistochemistry with anti-smooth muscle antibody supported the diagnosis of glomus tumor by demonstrating tumoral smooth muscle actin (Fig. ). At follow-up visits, no further radiological investigations were requested and no recurrence was noted. There was complete healing of the finger within 6 months and the nail regained its normal appearance in 10 months.
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pmc-6193310-1
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A 3-year-old Caucasian girl presented to the emergency room of a community hospital complaining of abdominal pain. After 3 hours, an abdominal X-ray showed a coin lithium battery (CR 2025) located in the fundus of her stomach (Fig. ); she was transferred to a referral pediatric hospital. After 6 hours, she developed massive hematemesis and severe hypovolemic shock. The indicated computed tomography (CT) scan was not done due to her severe hemodynamic instability, and the surgeon decided to perform esophagogastroscopy to directly diagnose and treat. She was then referred to the operating room. Urgent endoscopy was unsuccessful because of the large amount of blood and clots in her esophagus and in her stomach, which prevented the localization both of the bleeding site and of the coin battery. Consequently, an emergency laparotomy was attempted (8 hours after the presentation of symptoms), and the coin battery was manually identified in the gastric fundus. The surgeon then performed a gastrotomy to directly visualize the area of interest, remove the coin battery, and treat the presumable bleeding site. Despite removal of the coin battery from her stomach, and suturing of the burned area, the child still had hematemesis and hypovolemic shock. A Sengstaken–Blakemore tube was placed in order to stop further misunderstood esophageal bleeding sources along the transit area of the foreign body. She was then referred to our tertiary referral center, and directly to the operating room. Clinical conditions at admission were critical, multiple blood transfusions and high-dose vasopressors could not maintain her blood pressure. Endoscopy showed a massive bleeding localized in the medium esophagus (Fig. ). The Sengstaken tube was removed. To treat the massive esophageal hemorrhage, a 20 mm endoscopic dilation balloon (CRE PRO; Boston Scientific, EU) was inflated directly over the bleeding site. The partial reduction of the bleeding allowed an attempt at angiography, although there was a high clinical suspicion of AEF. Percutaneous cannulation of her left common femoral artery was attempted, followed by insertion of a 0.35 Bentson wire, advancement of a 5 Fr sheath, and insertion of a marker pigtail catheter. An aortogram was obtained in a left anterior oblique projection, and revealed extravasation of contrast, confirming the suspicion of an aortic rupture just above the diaphragmatic plane (Fig. ). The Bentson wire was retrieved, and an Amplatz Super Stiff™ wire (Boston Scientific, USA) was introduced. An 11 Fr sheath was then advanced over the wire and placed in her common femoral artery. Considering the life-threatening condition, an endovascular stent was released to stop the massive blood flow. A covered balloon-expandable stainless steel stent of 16 × 61 mm (Advanta™ V12; Atrium Medical Corporation, USA) was placed across the rupture in the thoracic aorta (Fig. ), and dilated up to 12 atm, which corresponds to a nominal pressure to avoid aortic wall injury. After the deflation of both balloons (endoscopic and angiographic), hemodynamic stability was achieved. A hemostatic endoscopic powder (Hemospray®; Cook Medical, Ireland) was sprayed directly on the residual bleeding sites, achieving complete hemostasis. During the entire procedure, our patient was given 2 units of packed red blood cells (estimated blood volume 1520 ml) []. The final angiogram revealed a resolution of the aortic leak, with a good expansion of the stent. She maintained hemodynamic stability, had palpable pedal pulse postoperatively, and was admitted to the intensive care unit, where her hematocrit level and hemodynamics remained stable. A CT angiography confirmed the correct placement of the aortic stent, and no evidence of leakage of contrast dye injected in the esophagus.
After 72 hours, the orotracheal tube was removed, and she started to breathe spontaneously again. After 1 week we endoscopically placed a nasoduodenal tube to start enteral feeding. Every 7 days, esophagogastroduodenoscopies (EGDs) were performed to follow the complete mucosal healing, and after 1 month, she started eating again, and was discharged home.
The 1-year endoscopic examination showed only complete re-epithelialization on the previous esophageal bleeding site (Fig. ). A 3-year follow-up was uneventful.
Four consecutive CT scans (one every 12 months) showed the correct position of the angiographic stent and no other pathologic signs.
Our patient is being followed-up by our cardiology team.
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pmc-6193329-1
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A 33-year-old male, without comorbidities, was admitted to the hospital on June 28th, 2017, reporting fever (39.5°C) and paresthesia in the feet upwards. He had difficulty in walking and speaking; he also related episode of the fall from his own height. He was admitted to the intensive care unit (ICU) with dyspnea, pneumonia, and complaints of persistent muscular pain. His initial laboratory tests showed hemoglobin 14.0 g/dL, white blood count 6.780/mm3, BUN 8.4 mg/dL, creatinine 0.72 mg/dL, Na 143mEq/L, K 4.2 mEq/L, CK 138U/L, and PCR 10.1mg/dL. On the second day of admission, serology was positive for Zika virus (IgG antibodies).
On June/30/2017, he developed acute respiratory insufficiency type II, requiring sedation and orotracheal intubation and was placed on mechanical ventilation with pressure controlled mode (PCV). Due to the severity of his clinical condition, he was maintained with this regimen until the beginning of the weaning process. His cerebrospinal fluid showed an increased presence of proteins (191mg/dL) with a normal cell count consistent with Guillain-Barré syndrome. Blood cultures for bacteria or fungi and serological tests for toxoplasmosis, herpes, varicella, and HIV were all negative. During his stay in the ICU, 0.4g/kg intravenous immunoglobulin was administered for 5 days without improvement. In the same period, the patient developed septic shock of undetermined focus, with vasoactive amines and intravenous antimicrobial agents being administered for 10 days (Meropenem combined with Fluconazole) according to the Campaign Surviving Sepsis and Latin America Sepsis Institute, ILAS.
The 840TM mechanical ventilator (Covidien-Nellcor and Puritan Bennett, Boulder, Colorado, USA) was used. The patient was tracheostomized after 48 hours of intubation, remaining for 25 days on mechanical ventilation in the ICU; after that, he was transferred to the prolonged ventilation unit after three unsuccessful attempts at conventional weaning trial with trach collar, in which he did not reach a spontaneous breathing higher than 15 minutes. At that time, the patient was awake, cooperative, hemodynamically stable, and free of infection. The IMT program using the electronic isokinetic loading device (POWERbreathe KH-2, London, UK) was started on day 26 of MV, in which 6 sets were done with 10 repetitions to achieve the 60 efforts daily intermittently and incrementally; see .
The muscle function of the patient at start of the training program evaluated by the Medical Research Council (MRC) scoring was 12 (20% of normal); the correspondent value using the functional status score (FSS-ICU) was 3 (8.6% of normal). By this time, his maximal inspiratory pressure (MIP) was 11cmH2O and the TIE index 0.27cmH2O/s, when the training load was adjusted to a maximum of 5 cmH2O (45% of the MIP). On day 36 of MV, his MIP had increased to 24 cmH2O with a TIE index of 0.65 cmH2O/s, a time when the training load was set to 12cmH2O (50% of the MIP). In the following week, the MIP reached 50cmH2O, the TIE index was 1.45 cmH2O/s, and the training load was set to 28cmH2O (56% of the MIP). On day 14 after the start of IMT, the patient was successfully weaned off the ventilator. A daily training with a load of 30cmH2O (60%) was maintained. On day 26 of IMT, his MIP was 85cmH2O and the TIE index 2.05cmH2O/s (). He was discharged from the ICU after 64 days.
The IMT program was accompanied by an early mobilization and physical therapy protocol, active member exercising in bed followed by resistance exercising against gravity at the bedside, evolving to moving to standing position. Hospital discharge took place on September 8th, 2017, totaling 71 days of hospitalization. By that time, the scoring values using the MRC assessment and the FSS-ICU scale were 34 (57% of normal) and 18 (51.4 of normal), respectively.
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pmc-6193347-1
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A 41-year-old Hispanic woman initially presented to the emergency room (ER) in 2012 with a severe excruciating headache for approximately 1 hour after the use of meth. Further history revealed patient had been an oral, snorting and intravenous user of meth. Her headache was also associated with nausea, vomiting, neck pain/stiffness, and photophobia. The patient had the following vitals: blood pressure 146/94 mmHg, heart rate 64 beats/min, respiratory rate 18 breath/min, and Temperature 36.5°C. The further patient assessment revealed a Hunt and Hess: grade I (+1) and Glasgow Coma Scale (GCS) of 15 with no focal deficits. Blood workup (hematological and blood chemistry) was within normal range. A head CT demonstrated left frontal intraparenchymal hemorrhage (IPH) measuring 1.2 × 2.6 cm with bilateral frontal and Sylvian fissure subarachnoid hemorrhage () with hemorrhagic extension into the fourth ventricle; Fisher grade: IV. CT-A demonstrated a left distal anterior cerebral artery aneurysm measuring 3.7 × 3.4 mm pointing in a superior-medial direction. An EVD was placed for obstructive hydrocephalus. After coiling the ruptured aneurysm, postcoiling images were also obtained (). After procedure the patient was stable and without neurological deficit; her ICU stay was uneventful and eventually discharged home.
The patient was lost to follow-up and presented in the hospital emergency room after four years with complaints of acute onset headache similar to prior presentation with headache and vomiting identical to the symptoms she had in 2012. Follow-up history revealed she continued to struggle with meth abuse with last use around ten days before her presentation to the hospital. Her vitals on presentation were as follows: blood pressure 129/54 mmHg, heart rate 61 beats/min, respiratory rate 16 breath/min, and Temperature 37°C. The patient was assessed as Hunt and Hess grade II + 1 and a GCS of 15 with no focal deficits. There was a left medial frontal intracerebral hemorrhage adjacent to an aneurysm that was coiled previously on head CT (). A formal angiogram demonstrated rerupture with recannulation at the base of the previously coiled aneurysm. Additionally, three neoaneurysms that were found include a periophthalmic aneurysm of the right internal carotid artery, approximately 5 mm, a fusiform dilation aneurysm at the pericallosal and callosomarginal bifurcation, and a basilar tip aneurysm, approximately 1.5-2 mm and 4 mm, respectively (Figures and ) and were assessed as Fisher grade IV. She subsequently underwent a bifrontal craniotomy for clipping of her complex anterior cerebral branch aneurysm. Her postoperative course was uneventful, and the patient was eventually discharged home, GCS 15, and neurologically intact.
Five days after discharge in 2016, the patient again presented to the hospital as a transfer from an outside hospital, intubated, with a head CT demonstrating a 3.7 × 5.2 × 5 cm left frontal intracerebral hemorrhage (ICH) with extension into the bilateral lateral ventricles, third and fourth ventricles (). The patient was Hunt and Hess grade IV + 1, Fisher grade IV. Urine drug screen was positive for meth (records from another hospital). On arrival, her vitals were as follows: blood pressure 143/67 mmHg, heart rate 61 beats/min, respiratory rate 18 breath/min, and Temperature 37.4°C, and GCS was 11T with left-sided hemiparesis. Emergent left craniectomy was done for evacuation of the intraparenchymal hemorrhage and ventriculostomy tube placement. Postoperative formal angiogram, less than 3 weeks from her previous cerebral angiogram, showed that the previously identified fusiform dilations associated with the right pericallosal and callosomarginal bifurcation segment now had a small saccular component with a neck of 5 mm and a height of 7 mm (). The previous periophthalmic, basilar tip and left frontopolar aneurysms were identified and remained unchanged. She subsequently underwent angiography assisted coiling of the right pericallosal and callosomarginal bifurcation aneurysm (). Over the remainder of her hospital stay, she underwent revision of cranioplasty as well as angiogram for pipeline stent of the periophthalmic artery aneurysm. She was downgraded out of the ICU, ambulating with physical therapy with the assistance of a walker and subsequently discharged home.
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pmc-6193354-1
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A previously healthy 39-year-old woman was referred to our hospital because of a cystic lesion in the liver demonstrated by abdominal ultrasonography (US). Laboratory studies, including liver function tests, and tumor markers were also within the normal limits. Serological markers for hepatitis B or C viral infection were undetectable. Abdominal US revealed a well demarcated, heterogeneously low-echoic mass 170 mm in diameter in right lobe of the liver. Abdominal computed tomography (CT) during hepatic arteriography (CTHA) revealed early ring enhancement in the peripheral area in the arterial phase and slight internal heterogeneous enhancement in the delayed phase (Figures and ). Magnetic resonance imaging (MRI) showed that the tumor had low signal intensity on T1-weighted images and some foci of high signal intensity on T2-weighted images. Gadolinium ethoxybenzyl (Gd-EOB) MRI revealed no uptake in the corresponding area (Figures , , and ). Abdominal angiography demonstrated a large avascular region in the liver corresponding to the tumor, although no typical features of cavernous hemangioma were evident (). 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal FDG uptake. With these radiological findings, malignant liver tumor could not be excluded, such as biliary cystadenocarcinoma, cholangiocarcinoma, mesenchymal tumors, and hepatocellular carcinoma associated with cystic formation.
The patient underwent posterior sectionectomy. Intraoperative examination revealed a relatively soft dark red tumor (); the resected specimen weighed 1.1 kg and measured as 170×100×80 mm. The cut surface of the tumor revealed a white, solid, and cystic mass that was elastic, soft, and homogeneous with a yellowish area considered to be myxoid degeneration (). Histological examination showed that the tumor mostly consisted of sclerotic area and cavernous hemangioma area is partly observed (). Sclerotic area presents diffuse fibrosis () and the typical histology of cavernous hemangioma was confirmed in some parts. In addition, marked increase and dilation of medium sized veins with cavernous form were frequently noted in the surrounding areas of tumor (). The increased and dilated veins show positivity of CD31 immunostaining being a marker of endothelium (). The pathologic features were consistent with sclerosing hemangioma. The postoperative course was uneventful, and the patient was discharged on postoperative day 10.
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pmc-6193570-1
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A 29-year-old male presented at our hospital with a history of chronic anemia since childhood. The patient underwent gastroscopy and colonoscopy with normal results. Due to the persistence of the anemia, despite symptomatic treatment with oral iron, it was decided to extend the study with imaging techniques. A simple abdominal X-ray was performed, and although at first it did not reveal any significant alterations, retrospectively, phleboliths were visualised in the right side of the pelvis (Figure ).
A small bowel study (SBS) with barium was also performed, and it showed in the distal ileum the poor distensibility and irregular contour (Figure ).
Because of these findings, computed tomography enterography (CTE) was performed, which showed phleboliths and transmural wall thickening in a 10-cm segment of the distal ileum with homogeneous contrast enhancement (Figure ).
No inflammatory changes were seen in mesenteric fat. No abdominal lymph nodes suggestive of malignancy were seen, and there was no involvement of adjacent organs.
Based on these findings, the most likely preoperative diagnosis was haemangioma of the distal ileum. A laparotomy and segmental small bowel resection was performed, which revealed a 10-cm ileum lesion that on pathology examination suggested a vascular nature due to its bluish purple coloration, compressibility, and presence of varices on its surface. The histopathological assessment revealed a vascular lesion compatible with haemangioma. After our patient recovered from surgery, he remained asymptomatic.
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pmc-6193799-1
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A 9-year-old boy, with previous anorectal malformation, corrected with a posterior sagittal anorectoplasty (PSARP), developed neuropathic bladder and bowel. He underwent an ileocystoplasty and Monti–Mitrofanoff and appendix ACE procedure. The tip of the macroscopically normal appendix was sent for routine histopathology, which is a standard practice for the operating surgeon.
Microscopy demonstrated a 5-mm well-differentiated neuroendocrine tumor in the tip of the appendix (
), which extended into muscularis propria. K
i
-67 tumor proliferation index was <2%. On hematoxylin and eosin (H&E) staining, nests of neuroendocrine cells could be seen infiltrating into the appendix wall and involved the proximal resection margin, and findings were confirmed on synaptophysin staining (
).
Due to proximal margin involvement and following neuroendocrine tumor multidisciplinary team (MDT) recommendation, the appendix conduit and surrounding skin was re-excised and a tube cecostomy was created through a separate incision. Microscopy of the remainder of the appendix revealed no residual neuroendocrine tumor, and no further treatment was required. The patient remained well at the last follow-up.
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pmc-6193800-1
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A 14-year-old previously healthy girl presented 2 weeks after an uncomplicated laparoscopic appendectomy for non-perforated acute appendicitis in a regional hospital. The girl complained of gradually reducing urinary frequency to twice per day and prolonged hesitancy. The micturition stream was initially weak and slow before becoming interrupted. Straining did not produce stronger urinary stream. She had never suffered from urinary tract infections (UTIs) or constipation and opened her bowels daily.
Following an episode of acute cystitis 2 months later, she completely lost her ability to void. She was put on indwelling Foley urinary catheter, and her cystitis was successfully treated with antibiotics. After every attempt to remove the urinary catheter, she had to be catheterized again with 300 to 1200 mL of urine volume registered. She noted loss of urge to urinate and felt only dull pain in suprapubic region and right iliac fossa on extreme bladder distention. The girl was kept on indwelling urethral urinary catheter and referred to a tertiary center to determine the etiology of her urinary retention.
She was examined with normal clinical findings and no obvious pathology on abdominal and pelvic ultrasound scan (USS). A pediatric neurologist found nothing abnormal, and magnetic resonance imaging (MRI) of the brain and spine, electromyography (EMG) of the lower extremity, somatosensory-evoked potentials (SEP) of tibial nerve, electroencephalogram (EEG), and lumbar puncture were with no pathology. On USS, the gynecologist described multiple follicular cysts on ovaries bilaterally and found no pathology explaining her urinary retention.
Our pediatric urologist performed an examination under general anesthesia including a free calibration of the urethra up to 26F followed by normal findings on cystoscopy. Videourodynamic study (VUDS) showed an asensitive and hypotonic bladder. The bladder filling had to be stopped at 360 mL due to the patient's discomfort. Maximum intravesical pressure achieved 11 cmH
2
O. When pulling the urodynamic catheter out of the bladder manually, the maximum urethral pressure measured was 120 cmH
2
O. On vesicocystourethrogram (VCUG), there was no vesicoureteral reflux, a smooth bladder wall and closed bladder neck (
).
Psychologic and psychiatric evaluation identified no major problem. During the following 2 years of repeated admissions to several regional and university hospitals, many of the tests described above were repeated, including an MRI of brain and spine with identical conclusions.
Clean intermittent catheterization (CIC) was recommended to the patient. However, because of poor tolerance of CIC due to frequent macroscopic hematuria and pain, a suprapubic catheter was placed. Thereafter, she suffered recurrent symptomatic afebrile UTIs caused by multi-resistant bacterial strains, e.g.,
Klebsiella
,
Pseudomonas
, or
Escherichia
. Finally, after 2 years, based on the history, symptoms, and urodynamic findings, she was diagnosed with Fowler's syndrome (FS).
For the treatment of FS, the patient was indicated for S3 neurostimulation. The implantation of two Medtronic S3 neurostimulators, type Interstim II, bilaterally in the upper gluteal region was performed under general anesthesia in two phases. The first phase was a transcutaneous implantation of the electrodes into S3 foramina and their connection to externalized neurostimulators. The first procedure took 30 minutes. As the patient restored her voiding completely back to normal when switching on the neurostimulators and experienced no side effects, she could undergo the second phase 4 weeks later—permanent subcutaneous implantation of the neurostimulators (
). The second procedure took 15 minutes under general anesthesia.
With a transcutaneous remote control, she was able to modify the intensity of stimulating current to avoid any discomfort (
). On the last follow-up, 4 months after the implantation, she voided four to six times per day with post-void residuals up to 50 mL on USS. Unfortunately, she suffered two prolonged episodes of burning on micturition even after the operation. On both occasions, she was diagnosed with acute cystitis by
E. coli
107 that was treated with antibiotics after sensitivity testing.
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pmc-6193805-1
|
An 85-year-old gentleman, known to suffer from hypertension and congestive heart failure but with no previous history of abdominal surgery, was admitted to hospital with a 3-week history of dysuria, severe urinary frequency, nocturia, suprapubic pain, fever, and increasing lethargy. He had been treated with antibiotics by his family doctor but symptoms failed to resolve. Urinalysis was indicative of a urinary tract infection with positive nitrites, proteinuria and leukocyturia but urine culture was negative. Blood tests revealed neutrophilia and mild acute renal impairment. The patient was admitted to a medical ward, started empirically on intravenous Ciprofloxacin, and discharged 2 days later on oral antibiotics, and a urological review was arranged.
He was readmitted 10 days later through emergency department Accident and Emergency (A&E) department, his symptoms persisting. At this point, he was referred to our unit. Again, no bacteria were cultivated from urine. Intravenous Co-Amoxiclav therapy was initiated. In view of these recurrent symptoms, an ultrasound examination of the urinary tract was performed. This showed a heterogenous mass containing gas, anterior to the urinary bladder measuring 8.5 × 4.9 × 6.1cm. To further characterize the findings on ultrasound examination, a computed tomography (CT) of the thorax, abdomen, and pelvis with intravenous contrast was requested. This showed a large, thick walled mass measuring 8cm superior to the urinary bladder, containing fluid and gas, communicating with the urinary bladder, and in contact with small bowel (
). Several enlarged lymph node groups, namely in both groins, lateral vesical groups bilaterally and left para-aortic region up to the level of the left renal hilum were noted.
A urinary catheter was inserted and ‘cloudy’ urine containing a sediment drained. Cystoscopy was performed primarily to localize the fistula and its relation to the ureteric orifices in preparation for extirpative surgery. At cystoscopy, the bladder was found to be full of debris and a fistulous opening was seen well away from both ureteric orifices. A Gastrografin enema of the rectum showed no leakage of contrast material from the colon into the urinary bladder.
Klebsiella oxytoca
and
Enterococcus faecium
were eventually cultivated from further microbiological examination of the urine.
The patient underwent laparotomy, during which a complex mass involving the proximal ileum and fundus of urinary bladder together with enlarged lymph nodes in the left obturator-inguinal region were found. The small bowel mass involving a wide fistula (approximately 3 cm diameter) was dissected off the dome of the bladder (
). The involved loop of ileum was resected and a stapled (GIA80 Covidien). Primary anastomosis was performed. A partial cystectomy was possible, circumscribing the fistula while leaving an adequate capacity bladder and preserving the trigone. A suprapubic urinary catheter and a urethral catheter were inserted for bladder drainage in the postoperative period which proved to be uneventful. A cystogram performed 3 weeks after the operation showed no leakage of urine and the catheters were removed. The patient was discharged from hospital a few days later, the total hospital stay being 5 weeks. Minimal discomfort was reported from urinary symptoms on discharge.
Histopathological examination of the resected tissues was reported as showing poorly differentiated urothelial carcinoma (pT4b). Both vascular and perineural invasion were identified. The tumor was transmural in the bladder specimen and ulcerated through the mucosa of the ileum. Resection margins were reported to be clear of tumor. Immunohistochemistry showed strong CK7, MNF116, and p63 expression. There was focal S-100 expression. There was no expression of CK20, CDX2, or Desmin.
Further to an oncologist evaluation, no further treatment was planned due to the patient's advanced age and comorbidities. He was hospitalized again 3 months after discharge suffering from a severe pneumonia to which he succumbed.
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pmc-6194315-1
|
A 65-year-old female presented with dizziness of 3 days duration. She had no history of hypertension, diabetes mellitus, and cardiovascular disease. Admission neurological examination was unremarkable. Electrocardiography showed no atrial fibrillation and transesophageal echocardiography showed no anomaly. Non-contrast head computed tomography (CT) demonstrated no significant infarction. Diffusion-weighted magnetic resonance imaging revealed acute multiterritorial infarcts in the left corona radiata, bilateral cerebellar hemispheres, and left pons (Figure ). Cervical color ultrasound examination demonstrated vulnerable atherosclerotic plaques at the origin of the left ICA (Figure ), and bilateral low flow with a high resistance flow pattern in both vertebral arteries while normal flow in the basilar artery. CT angiography of the head showed a left PHA, bilateral hypoplastic vertebral arteries, and no posterior communicating arteries (Figure ). The PHA arose from the cervical segment of the left ICA, ran upward, took a somewhat tortuous course, and continued as the ipsilateral vertebral artery through the left hypoglossal canal, thereby serving as the major contributor of the posterior circulation. Aspirin (100 mg/day) and atorvastatin (20 mg/day) combination therapy was instituted, and her neurological condition remained stable during 6-months follow-up.
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pmc-6194551-1
|
A 47-year-old man presented with hypokalemia and mild proteinuria owing to an unexplained syncope that occurred 8 years prior. He neglected his condition after taking oral medication to correct the hypokalemia. Three years ago, he manifested with severe proteinuria and was hospitalized in Shanghai Zhongshan Hospital. Serum creatinine (Cr) and albumin (alb) were 58 μmol/L and 22 g/L, respectively. Results from a 24 h urine protein excretion test detected 10.2 g of protein. Initial blood electrolytes, 24 h urine electrolytes, and the random UK/UCr ratio are shown in Table . Serological tests for infections and autoantibodies were negative. Physical examination, renal sonogram, and urogenital studies were normal. Neither hearing loss nor any ophthalmologic abnormalities were noted. He was diagnosed with nephrotic syndrome and a renal biopsy was performed.
Light microscopy showed previously unapparent proliferation of glomerular mesangial cells and mild segmental increases in the mesangial matrix (Fig.). There was no hypertrophy of the juxtaglomerular apparatus or significant interstitial fibrosis or tubular trophy. Electron microscopy revealed diffuse effacement of the foot processes and no other significant ultrastructural abnormalities. Immunofluorescence demonstrated no deposition of immunoglobulins (IgG, IgA, and IgM) or complement (C3, C4, and C1q), and the kappa and lambda chains were also negative. The renal pathology was consistent with the development of minimal lesions. The patient was treated with prednisone (60 mg/d) and achieved complete remission after 3 weeks of treatment. Prednisone was tapered and administered for a total of 19 months before drug withdrawal. However, the level of serum potassium was lower than normal, despite taking potassium agents (KCl: 1.5 g/d).
One year ago, the patient experienced a relapse coinciding with an upper respiratory infection and was admitted to our hospital. He had no particular past history. His parents were not consanguineous. His father had passed away without a confirmed cause of death. The patient’s elder brother was prone to hypokalemia after sweating. The mother and sister were both healthy. Physical examination revealed a sitting blood pressure of 109/72 mmHg. Cr and alb were 56 μmol/L and 45.3 g/L, respectively. The amount of 24 h protein excretion was 3.98 g. Blood electrolytes, angiotensin-II, 24 h urine electrolytes, and the random UK/UCr ratio are presented in Table . Rennin, aldosterone, and angiotensin-I levels were normal. The serum potassium was 3.46 mmol/L after taking 4 g/d KCl and 80 mg/d spironolactone, which reached a normal range after the intake of magnesium aspartate.
Genetic analysis was performed after informed consent had been obtained from the patient and his family members. KingMed Diagnostics was responsible for the sequence analysis. The method of sequencing was as below. Total DNA was extracted from blood peripheral leukocytes by the QIAamp Blood DNA Mini Kit (QIAGEN, America). Premier 5 software was used to design primers specific to coding regions in SLC12A3, CLCNKB, CLCNKA, SLC12A1, KCN1 and BSND, which were amplified by polymerase chain reaction and directly sequenced. DNA sequencing results were compared with the normal sequence (NM_000339.2, NM_000085.4, NM_004070.3, NM_000338.2, NM_000220.2, NM_057176.2) to identify any potential mutations. Databases of ESP6500, 1000 Genomics, HGMD, ClinVar, UniProt and dbSNP were searched to predict the location of disease-causing genes. SIFT, PolyPhen-2, LRT, Mutation Taster, Mutation Assessor, FATHMM, GERP, PhyloP and SiPhy softwares were employed to predict the pathogenicity of putative missense mutations. Net Gene2 Server and AUGUSTUS softwares were used to predict the pathogenicity of Splicing change. Sequence analysis of the SLC12A3 gene revealed a homozygous missense mutation in exon 6 (c.841 T > C), which is likely to cause an arginine substitution (for tryptophan) at codon 281 (p.Trp281Arg) (Fig.), and two heterozygous mutations in exon 15 (c.1568C > A; c.1551C > G) of the CLCNKA gene (Table ). The mutations in SLC12A3 and CLCNKA have not been reported in literature thus far. Bioinformatics software predicted the homozygous missense mutation of SLC12A3 had larger possibility of disease, and a new heterozygous missense mutation of CLCNKA (c.1568C > A in exon 15, p.Thr523Asn) was probably damaging and a heterozygous synonymous mutation of CLCNKA (c.1551C > G in exon15, p.Pro517=) had no obvious effect on mRNA splicing. No mutations were detected in any of the exons and exon–intron boundaries in the CLCNKB, SLC12A1, KCN1 and BSND genes.
|
pmc-6194553-1
|
A 28 year-old man was referred to our department for the treatment of tongue carcinoma. The etiology of dialysis-dependent end-stage kidney disease was Alport’s syndrome and the duration of hemodialysis treatment was 7 years and 9 months. His history included hypertension and anemia. No metastatic lymph node was palpable in the cervical region and the clinical diagnosis was tongue cancer. Partial glossectomy was performed (surgical time; 47 min (min), intraoperative bleeding loss volume; 63 ml). Intravenous second-generation cephalosporin 0.5 g was administrated just before the surgery. Intraoperative intravenous infusion volume of potassium-free solution was 200 mL (mean infusion speed at 20–40 mL/h). Routine hemodialysis was scheduled for 2 days before and after surgery, and then 3 times a week. We discussed patients’ conditions and perioperative dialysis management with nephrologists once a week during hospitalization. Erythropoiesis-stimulating agents (ESAs) were used on the day of hemodialysis during hospitalization. Nafamostat mesilate as an anticoagulant during hemodialysis was used from POD 1 to 7. From POD 1 to 5, the second-generation cephalosporin (0.5 g once daily intravenously) and the third-generation cephalosporin (0.2 g once daily per mouth) during POD 6 to 10 were administered. The healing process was uneventful and oral intake was resumed on POD 5. Daily limits of protein intake, salt intake, and liquid intake were 70 g, 7 g and 500 mL, respectively. The pathological diagnosis of surgical specimen was squamous cell carcinoma (SCC). No adjuvant therapy was performed. The patient was free of the disease 13 years after surgery.
|
pmc-6194553-2
|
A 37-year-old man, initially treated with partial glossectomy for tongue SCC, was referred to our department for recurrence. The cause of dialysis-dependent disease was chronic kidney failure, and the duration of dialysis treatment was9 years and 4 months. His medical histories were hypertension, anemia, secondary hyperparathyroidism, lacunar infarction, and hepatitis C. Oral examination revealed an endophytic tumor with mucosal ulceration on the left side of the tongue (Fig. ). Preoperative magnetic resonance imaging (MRI) demonstrated a tumor measuring 5.0 × 4.0 × 2.6 cm (Fig. ) and bilateral cervical lymph node metastasis. Tracheotomy, bilateral neck dissection, (ipsilateral: Level I-IV, contra lateral: Level I-III) and subtotal glossectomy were performed with abdominal vascularized flap reconstruction (surgical time; 10 h (h) 36 min, intraoperative bleeding loss volume; 514 mL). Intravenous second-generation cephalosporin 1 g just before the surgery was used and intraoperative intravenous infusion volume of potassium-free solution was 814 mL (mean infusion speed at 20–40 mL/h). Routine hemodialysis was scheduled for the day before and after surgery, and then 3 times a week. We discussed patients’ conditions and perioperative dialysis management with nephrologists once a week during hospitalization. ESA was used on the day of hemodialysis during hospitalization. Nafamostat mesilate was used from POD 1 to 7. From POD 1 to 5, the second-generation cephalosporin (1 g once daily intravenously) and the third-generation cephalosporin (0.2 g once daily per mouth) during POD 6 to 10 were administered. The healing process was uneventful and oral intake was restarted on POD 21. Daily limits of protein intake, salt intake, and liquid intake were 50 g, 5 g and 1500 mL, respectively. The pathological diagnosis of surgical specimen was SCC and four cervical lymph node metastasis (level II and level III at ipsilateral side, level II and level III at contra lateral side). Postoperative oral photograph is shown in Fig. . Pain control was achieved by using pentazocine hydrochloride and oxycodone hydrochloride hydrate. Adjuvant radiation therapy (50 Gy) was administered to the primary oral lesion and neck lesions bilaterally. Four months after the surgery, the primary tumor recurred, and he died 9 months later.
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pmc-6194553-3
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A 55 year-old man visited to our department for the treatment of lower gingival carcinoma. The etiology of dialysis-dependent end-stage kidney disease was Chronic glomerulonephritis and the duration of hemodialysis treatment was17 years and 6 months. Peptic ulcer and anemia had been treated. No metastatic lymph node was palpable in the cervical region and the clinical diagnosis was lower gingival cancer. Marginal mandibulectomy was performed (surgical time; 2 h 13 min). At the day before surgery red blood cells were transfused because of Hb value of 7.0 g/dL and a preoperative Ht value of 22.0% caused by gastrointestinal bleeding. We administrated intravenous second-generation cephalosporin 0.5 g just before the surgery. Intraoperative intravenous infusion volume of potassium-free solution was 250 mL (mean infusion speed at 20–40 mL/h). Routine hemodialysis was scheduled for the day before and after surgery, and then 3 times a week. We discussed assessment of patients’ conditions and perioperative dialysis management with nephrologists once a week during hospitalization. As POD 1 day after surgery, Hb and Ht levels were still low (Hb 6.5 g/dL, Ht 20.5%), and red blood cells were transfused per each day at POD on the 3, 6, and 8 days after surgery. By POD the 13 days after surgery, Hb and Ht levels improved (Hb 9.9 g/dL, Ht 31.0%). ESA was used on the day of hemodialysis during hospitalization. Nafamostat mesilate was used from POD 1 to 7. From POD 1 to 5, the second-generation cephalosporin (0.5 g once daily intravenously) and the third-generation cephalosporin (0.2 g once daily per mouth) during POD 6 to 10 were administered. The healing process was uneventful and oral intake was resumed on POD7. Daily limits of protein intake, salt intake, and liquid intake were 70 g, 7 g and 1000 mL, respectively. The pathological diagnosis of surgical specimen was SCC. The margin of the surgical specimen was free of tumor. No adjuvant therapy was performed. The patient was free of the disease 11 years after surgery.
|
pmc-6194553-4
|
A 72 year-old man was referred to our department for the treatment of subsequent cervical lymph node metastasis 4 months after brachy therapy of buccal SCC. For primary lesion, he received brachytherapy (first doze; 84Gy, second doze for tumor remaining; 83.97Gy) and external irradiation (30Gy). The etiology of dialysis-dependent end-stage kidney disease was chronic kidney failure after kidney cancer surgery and the duration of hemodialysis treatment was 1 year and 10 months. His history included hypertension, secondary hyperparathyroidism and anemia. Neck dissection (Level I-IV) was performed (surgical time; 4 h 49 min, intraoperative bleeding loss volume; 131 mL). Intravenous first-generation cephalosporin 0.5 g just before the surgery was used. Intraoperative intravenous infusion volume of potassium-free solution was 313 mL (mean infusion speed at 20-40 mL/h). Routine hemodialysis was scheduled for the day before and after surgery, and then 3 times a week. We discussed patients’ conditions with nephrologists once a week during hospitalization. ESA was used on the day of hemodialysis during hospitalization. Nafamostat mesilate as an anticoagulant during hemodialysis were used from postoperative day (POD) 1 to 7. From POD 1 to 5, first-generation cephalosporins (0.5 g once daily intravenously). Oral intake was restarted on the operative day. Daily limits of protein intake, salt intake, and liquid intake were 70 g, 7 g and 500 mL, respectively. The pathological diagnosis of surgical specimen was one cervical lymph node metastasis at Level II. Postoperative adjuvant chemotherapy was not administrated. Because of the general weakness caused by rapid progress of osteoradionecrosis of the mandible and disability of oral intake he could not come to our department and transferred to another hospital 1 year and 3 months after neck dissection.
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pmc-6194553-5
|
A 65-year-old man on hemodialysis was referred to our department for a mandibular tumor. The duration of hemodialysis treatment was2 years and 8 months. His medical history included diabetes, hypertension, cerebral infarction, diabetic retinopathy, and secondary hyperparathyroidism. On oral examination, a huge mass was observed in the right lower molar area extending to the left lower molar area (Fig. ). Panoramic radiography showed a well-defined radiolucent multilocular mass in the mandible (Fig. ). Segmental mandibulectomy and plate reconstruction were performed (surgical time; 5 h 9 min, intraoperative bleeding loss volume; 97 mL) (Fig. ). Intravenous second-generation cephalosporin (1 g) was administrated just before the surgery. Intraoperative intravenous infusion volume of potassium-free solution was 166 mL (mean infusion speed at 20–40 mL/h) and included glucose-insulin-potassium (GIK) therapy. Routine hemodialysis was scheduled for the day before and after surgery, and then 3 times a week. We discussed patients’ conditions and perioperative dialysis management with nephrologists once a week during hospitalization. ESA was used on the day of hemodialysis during hospitalization. Nafamostat mesilate as an anticoagulant during hemodialysis were used from postoperative day (POD) 1 to 7. From POD 1 to 5, the second-generation cephalosporin (1 g once daily intravenously) and the third-generation cephalosporin (0.1 g once daily per mouth) during POD 6 to 10 were administered. Wound healing was uneventful and oral intake was restarted on POD 13. Daily limits of protein intake, salt intake, and liquid intake were 60 g, 6 g and 800 mL, respectively. The pathological diagnosis of surgical specimen was ameloblastoma. No recurrence was observed during the follow-up period.
At 6 years after the first surgery, exposure of the plate was noted. We provided treatment options of plate removal alone, or reconstruction of an autologous bone graft. The patient chose the autologous bone graft. Diabetic control was poor (HbA1C 9.2%) and adequate blood glucose control was ensured with intensive insulin therapy. Preoperative computed tomography (CT) showed vascular calcification of the carotid arteries on both sides (Fig. ). However, the Doppler signals of the facial and superior thyroid artery to be anastomosed were observed. For the second surgery, plate removal and vascularized osteocutaneous scapular flap reconstruction were performed (surgical time; 9 h 42 min, intraoperative bleeding loss volume; 209 mL) (Figs. and ). Intravenous second-generation cephalosporin (1 g) was administrated just before the surgery. Intraoperative intravenous infusion volume of potassium-free solution was 1075 mL (mean infusion speed at 20–40 mL/h) and included GIK therapy. The schedule of routine hemodialysis, discussion with nephrologists, drug regimen of ESA, Nanafamostat mesilate and the antibiotics were the same as the first surgery. Red blood cells were transfused because Hb and Ht levels gradually decreased to 6.5 g/dL and 20.2%, respectively, on POD 7. Bone scintigraphy of radiolabeled 99mTc-methylene-diphosphonate imaging showed viability of the vascularized bone graft (POD 5), however, the scapular cutaneous flap began to necrosis on POD 9. Wound infection with methicillin-resistant Staphylococcus aureus (MRSA) was noted on culture. Vancomycin (0.5 g) was interveneously administered on the day of hemodialysis. Oral intake was uneventfully restarted on POD 14. The daily intake limits of protein, salt and liquid were the same as the first surgery. The scapular cutaneous flap underwent necrosis completely by POD 16 (Fig. ). On POD 37 we performed the necrotic tissue debridement and found the formation of granulation tissue on the surface of scapular bone (Fig. ). We performed the necrotic tissue debridement and split thickness skin graft on the scapular bone (surgical time; 1 h 22 min, intraoperative bleeding loss volume; 23 mL). Intravenous second-generation cephalosporin (1 g) was administrated just before the surgery. Intraoperative intravenous infusion volume of potassium-free solution was 23 mL (mean infusion speed at 20–40 mL/h). The schedule of routine hemodialysis, discussion with nephrologists, drug regimen of ESA, Nanafamostat mesilate and the antibiotics were the same as the first surgery and second surgery. Oral intake was restarted on the operative day. The daily intake limits of protein, salt and liquid were the same as the first surgery and second surgery. The healing process was uneventful (Figs. and ). The patient was free of the disease 3 years after surgery.
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pmc-6194572-1
|
A 46 year-old woman (gravida 2, para 2) with history of menometrorrhagia for 5–6 years due to a voluminous uterine fibroid was admitted to our institution (Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy) with fever (temperature over 39 °C) and strong pelvic pain.
Transvaginal ultrasound (US) showed diffuse fibromatosis and two evident uterine masses: the first was 53 × 57 mm, submucous, in fundus-anterior wall; the other was 97 × 70 mm, subserous, in isthmus-posterior wall. Despite the size of the masses, no alarming features were observed.
In order to preserve pelvic stability, the woman expressed the wish to avoid total hysterectomy; therefore, a laparoscopic myomectomy was considered.
During hospitalization the patient showed an inflammatory state (elevation of fibrinogen and C-reactive protein) with intermittent fever (not exceeding 38 °C). Blood cultures were negative.
Several measurements of serum LDH total activity were performed, showing normal or only slightly increased values, with the highest peak of 304 U/l (reference range: 125–243).
Due to the clinical presentation, an abdominal CT with and without contrast was performed, showing increased uterine volume with two evident masses: the smaller one (4 × 3 cm) was subserous, on the fundus; the larger one (12 × 10 cm), voluminous and inhomogeneous, was para-uterine, on the left, with intraligamentary growth and eccentric areas of colliquative necrosis (Fig. ). These features were suggestive of sarcomatous degeneration, so a MRI was recommended.
The abdomino-pelvic MRI was performed with and without contrast, confirming the presence of both masses (3.2 × 5 cm and 15x10x9 cm). However, the larger one appeared capsulated and non-infiltrative (Fig. ). Characteristic MRI findings associated with sarcomas were not clear: enhanced signal intensity (SI) was absent in T1, and weak and inhomogeneous in T2. These findings were not enough to support the diagnosis of uterine sarcoma.
In order to support our suspicion of malignancy, electrophoresis of LDH isoenzymes was performed, showing the following results: LDH1 = 15.6% (reference range: 16.1–31.5%); LDH2 = 23.3% (29.2–41.6%); LDH3 = 21.0% (17.0–26.2%); LDH4 = 13.6% (5.9–12.3%); LDH5 = 26.5% (3.2–17.3%); LDH5/LDH1 ratio = 1.7 (normal value: < 1).
We found an elevation of muscle isoforms (4 and 5) accompanied by a decrease of the normally predominant heart isoforms (1 and 2), with an increased LDH5 to LDH1 ratio. In literature, this pattern has been presented as strongly associated with malignancy [].
Given the characteristic LDH isoenzymes pattern, supported by the CT report, we discussed with the patient about the increased suspicion of malignancy and the necessity of a radical surgical treatment. So, we finally opted for a total abdominal hysterectomy instead of a laparoscopic myomectomy (initially preferred by the patient), in order to avoid risks linked to the morcellation of an occult malignancy (Fig. ).
Histological examination of the surgical sample showed a malignant mesenchymal proliferation constituted by hypercellular areas with epithelioid or pleomorphic cells (Fig. ) alternating with hypocellular myxoid areas (Fig. ). Necrosis and high mitotic index were observed. Immunohistochemistry showed positivity for caldesmon, muscle specific actin and CD10 and focal positivity for smooth muscle actin (Fig. -). The definitive diagnosis was of high grade leiomyosarcoma with myxoid changes, confirming our suspicion.
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pmc-6194589-1
|
A 36-year-old female (proband, II-2, Fig. ) had reported to the Department of Oncology, Thu Duc hospital (Ho Chi Minh City, Vietnam) with recurrence of frequent diarrhea and stool mixed with blood and mucus. Endoscopy revealed 100–1000 colonic polyps with the size in range of 5–15 mm (Fig. ). Colonic polypectomy was later performed to prevent the development of colonic cancer. Family history investigation revealed that the proband’s father died of colorectal cancer at the age of 51 year. Endoscopic screenings were therefore performed on all of her siblings. Two of her four siblings (II-5 and II-6) also exhibited 100–1000 colonic polyps suggesting of FAP syndrome in this family (Fig. ). These patients did not exhibited other non-colonic manifestations such as congenital hypertrophy of the retinal pigment epithelium (CHRPE) or desmoid tumors.
To identify the genetic mutation(s) that might have caused the FAP in this family, a MPS-based oncoSure hereditary cancer test (Gene Solutions, Vietnam) was chosen to perform on all nine members of the family including the proband, her spouse, all of her siblings and their spouses as well as their offsprings. The oncoSure hereditary cancer test is a 17-gene panel including BRCA1, BRCA2, PALB2, PTEN, TP53, CDH1, MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, STK11, VHL, RB1, RET that identifies an elevated risk for 10 hereditary cancers: breast, ovarian, colorectal, endometrial, gastric, pancreatic, prostate, melanoma, endocrine and retinoblastoma. Blood samples were collected and genomic DNA were extracted with QiaAmp DNA blood mini kit from Qiagen (Hilden, Germany) following the manufacturer’s instructions. DNA fragmentation and library preparation were done using NEBNext Ultra II DNA Library Prep Kit from New England BioLabs (Ipswich, MA, USA). Pool of sequencing libraries was captured using predesigned probes for 17 target genes from IDTDNA (Coralville, IA, USA). The targeted sequences covered all exons and a small flanking sequence of introns. Captured products were amplified with KAPA HiFi HotStart ReadyMix from KAPA Biosystems (Wilmington, MA, USA). Samples were sequenced on Illumina MiniSeq platform (Illumina, San Diego, CA, USA). Raw sequences from each sample were aligned to the reference human genome from University of California, Santa Cruz (UCSC) Genome Browser (NCBI build GRCh38) using Burrows Wheeler Aligner (BWA) []. The aligned output was used to compute depth and breadth of coverage in the target region, and SNP/INDEL calling with GATK standard pipeline []. Variants were classified using ClinVar database (National Institutes of Health).
A heterozygous deletion c.3927_3931delAAAGA (p.Glu1309Aspfs) in the APC gene was found in the proband (II-2), all other affected members (II-5 and II-6) and a young male member in the third generation (4 years of age, III-2). No other pathogenic or likely pathogenic mutations was detected elsewhere in the genes targeted by the oncoSure hereditary cancer gene panel. This deletion was absent in all unaffected members (II-3 and II-7) and a 5 year-old third generation male member (III-1) (Table ). We did not identify this mutation in the 50 normal control of the same ethnic origin and age range.
This 5-bp deletion occurs at codon 1309 which causes frameshift and creates a premature stop codon at position 4 of the new reading frame, resulting in the replacement of the last 1535 amino acids of APC by three incorrect amino acids. This variant was predicted to cause loss of normal protein function through protein truncation. The truncated protein caused by this deletion is similar to that caused by another 5-bp deletion variant (NM_000038.5(APC):c.3920_3924delTAAAA) which was reported in two individuals for whom clinical APC testing was ordered (Evidence detailed provided by GeneDx in ClinVar).
To confirm this novel heterozygous deletion, we performed PCR and Sanger sequencing for all tested cases. We designed primers flanking the deletion location using the reference human genome from UCSC Genome Browser. The primers (5’-ATCAGACGACACAGGAAGCA-3′ and 5′- ACTCAGGCTGGATGAACAAGA-3′) were synthesized and purified by IDTDNA (Coralville, IA, USA). PCR amplification was prepared using Q5 High-Fidelity 2× Master Mix from New England BioLabs (Ipswich, MA, USA) following manufacturer’s instructions. The PCR products were sequenced using Applied Biosystems 3500xl. As shown in Fig. , the 5-nucleotide deletion was found in the proband but not in the unaffected member, confirming our finding using MPS technology.
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pmc-6194605-1
|
A 72-year-old female patient had adult spinal kyphosis and showed a postural imbalance such as leaning forward or to the left side when walking and standing, resulting in claudication within 2 min. She underwent surgery including LIF at L2–3, 3–4, and 4–5 disc levels and posterior lumbar interbody fusion at L5–S1, and posterior corrective fusion from T10 to the ilium with bilateral S1 pedicle screws and bilateral dual iliac screws. It took 7 h and 18 min in surgical time and 179 ml of blood given intraoperatively (Fig. ).
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pmc-6194610-1
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A 53-year-old Japanese woman was diagnosed with lung adenocarcinoma (pT1aN0M0, Stage IA) harboring an ALK rearrangement and had been administered crizotinib after postoperative recurrence. She had a history of diabetes mellitus. Follow-up CT revealed mediastinal lymph node metastasis indicating tumor progression and then ceritinib was started. One month after ceritinib treatment, fever, an increase in the serum IL-18 level, inflammatory markers (CRP and IL-6) and bile tract enzymes (ALP and γ-GT) was observed (Fig. , ). To evaluate the cause of the elevated bile tract enzymes, we next performed a liver biopsy and the patient was diagnosed as ceritinib-induced cholestasis from the pathological examination of her liver tissue. Then, ceritinib was discontinued and we also started treatment with prednisolone to attenuate the inflammatory responses in the bile duct caused by ceritinib. However, though fever and the serum levels of CRP and IL-6 decreased with the treatment, the serum levels of IL-18 and hepatobiliary enzymes increased together with the expansion of the intrahepatic bile duct on CT and MRI (Fig. ) even two months after the discontinuation of ceritinib. After 9 months, the serum IL-18 had increased more together with the progression of the bile duct dilation and the appearance of biloma on CT and MRI (Fig. ). To determine the source of serum IL-18, we evaluated the expression of IL-18 in the liver by immunostaining. IL-18 positive cells were detected in the inflammatory sites around the interlobular bile duct of the liver tissue (Fig. ).
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pmc-6194612-1
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A 44-year-old Asian man with a medical history of chronic sinusitis and IgG4-related ophthalmic disease who was prescribed 5 mg of oral corticosteroids (prednisolone) 2 years previously (initial dose was unknown) was transported to our hospital with dyspnea lasting for several hours. He smoked cigarettes 24 pack years but did not have a history of intravenous drug abuse, heavy drinking, or poor dental hygiene. He had not undergone dental procedures recently. On arrival, his Glasgow Coma Scale score was 11 (eye, 3; verbal, 2; motor, 6), body temperature 37.1 °C, his respiratory rate was 28/min, his blood pressure was 99/42 mmHg, and his heart rate was regular at 150 beats/min. His symptoms were not obvious because of his consciousness disturbance; his face had no skin erythema or swelling, and his neck induration could not be palpated. A purpuric eruption was covering both of legs. Transthoracic echocardiography showed a hypercontractile left ventricle without pericardial effusion, regurgitation of valves, and vegetations. Contrast enhanced computed tomography (CT) showed no obvious embolization at the bilateral pulmonary arteries, but revealed left lung ground glass opacity, and bilateral irregular lung opacities without cavitation. Fluid retention at the right maxillary sinus was also found. Laboratory test results were as follows: leukocyte count, 19,100 cells/μL; hemoglobin level, 15.7 g/dL; platelet count, 0.6 × 104 cells/μL; creatinine level, 4.1 mg/dL; total bilirubin level, 3.9 mg/dL; C -reactive protein level, 45.6 mg/dL; procalcitonin level, 44.7 ng/mL; β-D-glucan level, < 6.0 pg/mL; a negative pneumococcal urinary antigen test; a negative Legionella urinary antigen test; prothrombin time international normalized ratio, 1.15; fibrin degradation products, 103 μg/mL; Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scores, 7 points; and Sequential Organ Failure Assessment (SOFA) score, 15 points. Blood gas analysis results were as follows (10 L/minute O2 administered): pH, 7.174; PaCO2, 32.7 mmHg; PaO2, 177 mmHg; HCO3, 11.6 mmol/L; lactate 13.8 mmol/L; anion gap, 16.7 mmol/L. Owing to suspected bacterial pneumonia-induced septic shock and/or purpura fulminans, endotracheal intubation was performed, and fluid resuscitation was started immediately. After we obtained blood, sputum, and urine cultures, initial empiric antimicrobial drugs (meropenem, clindamycin, and vancomycin) were administered. Norepinephrine was initiated, titrated up to 25 μg/min. In addition, vasopressin 0.03 U/min, dobutamine 8 μg/kg/min, and hydrocortisone 200 mg/day were also added for continuous infusion. Because mean blood pressure could not be maintained at 50 mmHg despite adequate drip infusion and high dose vasopressors, venoarterial extracorporeal membrane oxygenation (VA-ECMO) was initiated due to refractory septic shock. Continuous hemodiafiltration (CHDF) was also introduced due to severe lactic acidosis, and recombinant thrombomodulin was administered for sepsis induced DIC. After the patient was admitted to the intensive care unit, his vital signs stabilized gradually. Both VA-ECMO and CHDF were tapered on day 2 post admission. Norepinephrine, vasopressin, and dobutamine were tapered on day 3, 4, and 5, respectively. Repeat contrast enhanced CT confirmed bilateral lung nodules, left internal jugular vein and vertebral vein thrombosis; following this Lemierre’s syndrome was diagnosed on day 6 (Figs and ). Although the primary focus of the infection was thought to be the right sinus, purpura worsened on both legs. He then went into shock again on day 6 (Fig. ). Additional soft tissue infections were suspected; therefore, bilateral below the knee amputations were performed for source control. In addition to intravenous antibiotics, edoxaban (non-vitamin K antagonist oral anticoagulant) was initiated for left internal jugular and vertebral venous thrombosis. Following this, his vital signs improved without further systemic embolism. Cultures of the exudates from the skin lesions and histopathological samples did not identify any pathogens, and histopathological findings showed arterial thrombosis, and therefore, it was thought that second time shock developed due to purpura fulminans in the context of the septic shock and DIC. A tracheotomy was performed on day 13, and intravenous antibiotics and edoxaban were discontinued on day 59 with disappearance of the neck thrombosis, and bilateral lung nodules and fluid retention at the right maxillary sinus as identified on repeat CT. Lastly, he was transferred to another hospital for rehabilitation on day 121.
Gram-negative coccobacilli and gram-positive cocci were yielded from two sets of blood culture bottles (BacT/ALERT, bioMérieux, Marcy l’Etoile, France), which were taken prior to antibiotic administration. The gram-negative coccobacilli were identified as E. corrodens by ID Test HN-20 Rapid (Nissui Pharmaceutical Co., Ltd., Tokyo, Japan) (profile: 5220000, %ID 99.9%) and susceptibility testing was determined by Etest (bioMérieux) in Mueller-Hinton agar plates (bioMérieux) (Table ). These gram-positive cocci were catalase-negative and showed weak-beta hemolysis on 5% sheep blood agar (Nihon Becton-Dickinson, Tokyo, Japan), initially suspected as pyogenic streptococci, after 48 h of incubation under anaerobic and 5% CO2 gas at 35 °C. This strain was not identified by the rapid ID 32 STREP system (profile 00002500000; low discrimination of Erysipelothrix rhusiopathiae/Gemella hemolysans/Gemella morbillorum, bioMérieux) but was identified as G. morbillorum by BD BBL Crystal GP (profile: 0500000100, %ID 98.5%, Becton-Dickinson, Sparks, MD, USA). It was identified as G. bergeri with a score value of 2.068 (species level) by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS, Autoflex II with MALDI Biotyper software ver 3.1; Bruker Daltonik GmbH, Bremen, Germany) and confirmed by 16S rRNA gene sequencing by the method described previously []. Phylogenetic analysis results are shown in Fig. . Susceptibility testing was then performed with MicroFAST Type 7 J Panels and MicroScan Walkaway-96 (Beckman Coulter, Brea, CA, USA). According to the Clinical and Laboratory Standards Institute (CLSI) document M45-A3 (Clinical and laboratory standards institute. Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria, 3rd edition, CLSI guideline M45. Clinical and laboratory standards institute, Wayne, PA. 2015), results of minimum inhibitory concentrations of various antimicrobials and interpretation of susceptibility testing are shown in Table . Based on these susceptibility results and negative results of additional blood cultures on day 6, antimicrobials started empirically were changed to ampicillin-sulbactam on day 10.
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pmc-6194623-1
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A 79-year-old woman initially presented with diabetes in 2008. Her HbA1c level was 8.8%, and treatment with an oral hypoglycemic agent was initiated. At that time, the patient also reported swelling on the anterior surface of her neck in the area of the thyroid gland; therefore, she sought consultation at an ambulatory otolaryngology clinic. She was diagnosed with papillary thyroid carcinoma with metastasis to the right cervical lymph nodes. In 2011, a pulmonary tumor was detected; it was resected via thoracoscopy and a diagnosis of metastatic thyroid cancer was confirmed. In December 2012, her serum creatinine level was 0.57 mg/dL, with no evidence of proteinuria. In 2013, the patient underwent resection of the right lobe of the thyroid gland, including bilateral dissection of the paratracheal lymph nodes and the right parotid lymph node.
In January 2016, the patient experienced exacerbation of her unresectable thyroid cancer; therefore, oral administration of 10 mg lenvatinib was initiated.
The findings of the pretreatment laboratory assessment were as follows: normal blood pressure (118–132/64–77 mmHg); creatinine (Cr), 0 .72 mg/dL; and albumin (Alb), 3.8 g/dL, respectively, and her estimated glomerular filtration rate (eGFR) was 58 mL/min/1.73 m2. In addition, the urine sample test showed negative results for red blood cells (1–4/HPF), and the urine qualitative analysis showed negative results for protein. However, after initiation of treatment (Fig. ), the patient developed hypertension that required treatment with candesartan (8 mg/day). By February 2016, her Cr level had increased to 0.82 mg/dL, and her eGFR and Alb levels had decreased to 51 mL/min/1.73 m2 and 3.5 g/dL, respectively. She also developed hypertension (blood pressure, 140–170/60–70 mmHg). Based on these findings, we added a daily dose of amlodipine (5 mg/day) to her treatment; thereafter, the dose was increased to 10 mg/day. By March 2016, her Cr level continued to increase to 0.84 mg/dL, and her eGFR and Alb level continued to decrease (49 mL/min/1.73 m2 and 3.0 g/dL, respectively). Her blood pressure increased to 150/60 mmHg, and the candesartan dose was increased to 12 mg/day. However, she developed lower limb edema. In April 2016, she was diagnosed with acute kidney injury and nephrotic syndrome. Development of generalized edema and weight gain were noted, her Cr level increased to 1.17 mg/dL, and her eGFR decreased to 34 mL/min/1.73 m2. Measurements of other relevant parameters were as follows: total protein (TP), 5.1 mg/dL; Alb, 2.5 mg/dL; total creatinine (TC), 329 mg/dL; low-density lipoprotein (LDL), 204 mg/dL; and urinary protein, 11.78 g/gCr. The patient was referred to our institution for further evaluation and treatment.
On admission, the patient’s medications included lenvatinib (10 mg), glimepiride (0.5 mg), pioglitazone (915 mg), alogliptin (925 mg), candesartan (12 mg), and amlodipine (10 mg). On physical examination, her height was 155 cm, weight was 55 kg (usual weight, 44 kg), body mass index was 21.4 kg/m2, blood pressure was 142/60 mmHg, heart rate was 72 beats/min, temperature was 36.2 °C, and respiratory rate was 20 breaths/min. A surgical scar from her thyroidectomy was visible on the anterior aspect of her neck. In addition, bilateral edema of her lower limbs was evident. Significant medical history included a uterine myoma, appendicitis, and a fundal hemorrhage due to diabetic retinopathy at the ages of 50, 51, and 77 years, respectively. Her family history was negative, and she had no known allergies. The patient was a non-smoker and only consumed alcohol socially. Her urine and blood laboratory data are summarized in Table . Large quantities of urine protein and urine occult bleeding, anemia, renal function disorder, hypoalbuminemia, and hypercholesterolemia were observed. Urinary Bence-Jones proteins, increased ferritin, hypergammopathy, low-complement blood symptoms, and ANCA and ds-DNA antibodies were not observed, however.
Multiple pulmonary metastases were observable on computed tomography (CT) imaging. Although there was no evidence of malformation of the kidneys, generalized edema and thoraco-abdominal fluid were observed.
Considering the development of elevated blood pressure and nephrotic syndrome after administration of lenvatinib, drug-induced nephrotic syndrome was suspected as the primary clinical diagnosis. Therefore, lenvatinib treatment was discontinued.
The patient’s diabetes was controlled well with the use of oral hypoglycemic agents (HbA1c of 5.7%). However, her blood pressure remained high at 140–145/50–60 mmHg despite treatment with oral antihypertensive agents. Because of her history of diabetic retinal hemorrhage, papillary thyroid carcinoma with relatively new onset of distant metastasis, hematuria, low selectivity index (0.247), information based on the negative findings of hypocomplementemia, absence of MPO-ANCA, PR3-ANCA, ds-DNA antibodies, we thought that minimal change nephrotic syndrome (MCNS), membranoproliferative glomerulonephritis (MPGN), and rapidly progressive glomerulonephritis (RPGN) would not be correct diagnoses.
Because it is necessary to differentiate FSGS from diabetes nephrosis syndrome and secondary membranous nephropathy due to a malignant tumor, and because most TKIs are type I or type II and lenvatinib has novel binding ability (type V), we performed a renal biopsy.
Renal biopsy using light microscopy (Fig. ) revealed that 7 of 16 glomeruli had complete hyalinization, and that glomeruli with incomplete hyalinization showed partial glomerular collapse (arrow in Fig. ); FSGS was confirmed because the glomeruli showed lobular and segmental expansion. Vacuolar degeneration of the podocytes (see arrow in Fig. ) and enlarged endothelial cells with a thickened loop were evident, suggesting endothelial injury (arrow head in Fig. ). Thrombotic microangiopathy was absent. The mesangial matrix slightly increased, but the mesangial cells did not increase (Fig. ). Periodic acid methenamine silver (PAM) staining showed mesangial interposition-like changes and a duplicated basal membrane (arrow head in Fig. ). The endarterium was slightly thickened and the arterioles showed partial hyaline consolidation.
Immunofluorescence (Fig. ) of the IgG showed nonspecific staining, no linear pattern, and negative results. Only IgA, IgM, C3, and C4 were granular and slightly positive in the mesangial areas, and there was no staining of the loop wall. C1q was negative.
Vacuolar degeneration of podocytes (arrow in Fig. ) was observed on electron microscopy (Fig. ). The loops were thickened and a duplicated basal membrane was observed. Mesangial interposition-like changes were found (arrow in Fig. ), and endothelial cells invaded the basal membrane (arrow head in Fig. ).
Electron-dense deposits suggesting immune complexes were not observed. Foot process effacement was almost 60–70%. It suggested that this is a case of podocytopathy and not a secondary effect of hypertensive/hyperfiltration injury.
The mesangial matrix slightly increased, but there was no nodular glomerulosclerosis such as a Kimmelstiel-Wilson lesion or IgG immunofluorescence staining with a linear pattern along the basement membrane, thereby suggesting that the diagnosis was not advanced stage disease that could lead to diabetes nephrosis syndrome. The glomeruli showed lobular expansion, but mesangial cells were not increased and an electron-dense deposit was not observed; therefore, the diagnosis was not MPGN.
With regard to morphologic variants of FSGS based on the Columbia classification, the collapsing variant of FSGS is diagnosed because of the presence of collapsed glomeruli.
Treatment included the discontinuation of lenvatinib, dietary modifications, and the use of palliative diuretics. The patient’s weight decreased over the course of the subsequent 2 weeks (loss of 8.7 kg from admission weight) but showed improvement in the edema of her lower limbs. Glycemic control was achieved. Because nephrotic syndrome was improved after discontinuation of lenvatinib therapy, and because diabetic changes in the kidneys including increased thickness of the mesangial matrix were mild, we confirmed a diagnosis of secondary FSGS caused by lenvatinib.
The patient was discharged on day 11 after admission. Although her renal function status did not improve from that on admission (Cr, 1.16 mg/dL; eGFR, 35 mL/min/1.73 m2) to that at discharge (Cr, 1.17 mg/dL; eGFR, 34 mL/min/1.73 m2), her proteinuria did improve from 11.8 g/day on admission to 5.4 g/day at discharge. She was followed-up on an outpatient basis, and her proteinuria continued to gradually decrease over time. In July 2017, her Cr level was 1.04 mg/dL and eGFR was 39 mL/min/1.73 m2, with complete remission of urinary protein (qualitative urinary protein, 116 mg/gCr) and no evidence of hematuria. A period of 15 months was required to achieve complete remission after discontinuation of lenvatinib treatment. Chronic kidney disease (CKD; stage G3bA1) was diagnosed. Regular follow-up examinations are performed at our outpatient clinic.
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pmc-6194630-1
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A 37-year-old Moroccan patient, housewife, with treated latent syphilis, a non-smoker or alcohol drinker, diagnosed with NF1 on the basis of clinical features (more than six cutaneous coffee-milk spots, multiple neurofibromas, axillary lentigines, and mother as well as the sister and brother with NF1), presented with paroxysmal pain following exposure to cold or pressure on the fourth right subungual finger and in the palmar face of the first phalanx of the fourth right finger, for which she was taking a first-level analgesic. Clinically, the nail and its bed were almost normal; examination showed two painful subcutaneous tumors of approximately 0.5 cm in both locations, with gentle examination and palpation of the two tumors eliciting paroxysmal pain that did not allow a careful examination (Figs. and ).
Following block anesthesia of the finger, an oblique incision was made at the level of the proximal fold of the nail. With partial elevation of the nail plate, the subungual tumor had a red-blue color (Fig. ). Perioperative dermoscopy showed a purplish-red area reminiscent of a glomus tumor and elucidated the limits of extension of the tumor. Dermoscopy also guided the excision, which was made by removing the tumor encapsulated under the matrix of the nail; the latter was sutured after complete removal of the lesion (Fig. ). The second tumor on the left hand was yellow-buff, suggestive of a schwannoma (Fig. ). The histological examination of the first tumor confirmed the diagnosis of glomus tumor (Fig. ), whereas the second was diagnosed as a glomangiomyoma-type glomus tumor (Fig. ). The tumor cells were arranged around numerous narrow vascular slits that circumscribed flattened endothelial cells. These vessels were surrounded by several superimposed layers of ovoid cells with round, regular nuclei and moderately acidophilic cytoplasm. In some places, these elements deviated from the vascular walls and spread irregularly, sometimes isolated or in small clusters within a fibrous stroma, edematous, or myxoid. The histological examination of the second tumor eliminated the diagnosis of schwannoma and showed morphological aspects substantially comparable to the first tumor, with some peculiarities, including the presence of a fibrohyalin stroma and especially abundant myxoid. In some areas, the drawn vessels with irregular cavities were surrounded by thick smooth muscle without surrounding cell proliferation. In the superficial and middle dermis, a proliferation of glomic cells was observed around the vessels. These anatomopathological aspects were compatible with glomangiomyoma glomus tumor. Postoperative control showed a dramatic improvement in pain. The postoperative follow-up for 2 years was uneventful and the symptoms disappeared completely without recurrence and without deformation of the nail.
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pmc-6194636-1
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Mr. T, a 41-year-old Taiwanese man, with educational level of 12 years, suffering from schizoaffective disorder for more than 10 years, ever hospitalized to psychiatric wards for 7 times due to disease relapses, despite of more than 2 antipsychotic trials. Before this episode, he had been treated with clozapine 100 mg and lithium 900 mg daily with fair compliance and no remarkable side effects for 2 years. He was obese (body mass index, 39 kg/m2), but a lifelong non-smoker with no alcohol or substance abuse, no systemic disease in his medical history and no other comorbid psychiatric disease like personality disorder. He lived with his parents, was unemployed, and was capable of doing simple housework at home.
One day, the patient was sent to the emergency room of a medical center because he had been hearing voices for more than one week. Initial examinations indicated stable vital signs and normal laboratory results, electrocardiogram, and plain chest film. The patient was admitted to the psychiatric unit.
After admission, he was observed to be talking to himself and to have an elevated mood, auditory hallucinations of commanding voices, referential and persecutory delusions, and the hyperactive and agitated behaviors of squatting, standing up, crawling on the ground, and violently attacking others. Some excited catatonic symptoms were also noted, including restlessness, stereotypy, impulsivity, and combativeness. With regard to controlling his agitation and violence symptoms, he was managed with protective restraints and injected lorazepam 2 mg 1 ampule and haloperidol 5 mg 1 ampule intramuscularly, a total of six doses in the first week. A primary regimen of lithium 900 mg/d and clozapine 100 mg/d was used and titrated up to 175 mg/d. Two days after clozapine titration, the patient developed acute cardiopulmonary symptoms, including cold sweats, chest tightness, orthopnea, and tachycardia. Lab results showed elevated cardiac enzymes of CK-MB 37.7 ng/mL, troponin I 3.328 ng/mL, increased WBC 16500/mm3, and increased creatine kinase 8045 U/L with 100% MM form. Electrocardiogram showed sinus tachycardia and ST-segment depression in V1–V4. Due to suspected acute non-ST elevation myocardial infarction, the patient was transferred to the cardiac care unit (CCU), where he was managed with enoxaparin subcutaneously and dual antiplatelet agents (DAPT), and the antipsychotics and lithium were discontinued.
His catatonia symptoms persisted, and the patient scored a 20 on the Bush–Francis Catatonia Rating Scale (BFCRS) []. A diazepam intravenous drip (10 mg/500 ml infused in normal saline at a rate of 1.25 mg/h) and oral-form lorazepam 4 mg/d were administered []. With this treatment, the BFCRS score became 0. After staying 3 days in the CCU, the coronary angiography was reported as being normal, and the enoxaparin and DAPT were discontinued. With a relatively stable physical condition, the patient was transferred back to the psychiatric unit.
However, 3 days after discontinuing enoxaparin and DAPT, the patient suddenly collapsed after defecating in the psychiatric ward. He was resuscitated for 5 min, regaining his pulse, and presented with hypoxia with 80% saturation under Ambu bagging. Laboratory testing showed an elevated d-dimer level > 35 mg/L FEU. The electrocardiogram showed sinus tachycardia and ST depressed at precordial leads V1 -V4. The patient was immediately intubated and once again transferred to the medical ICU. During the second ICU stay, which lasted 7 days, the patient gradually improved and was extubated. While the chest computed tomography reported multifocal filling defects in the bilateral pulmonary arteries, which is in line with a pulmonary embolization, oral rivaroxaban 30 mg/d was given, and the patient was sent back to the psychiatric ward. Since the patient presented with refractory psychotic symptoms and severely agitated behaviors, which may have disturbed his physical recovery, clozapine was prescribed again with an initial dose of 50 mg/d, and the dosage was carefully titrated up to 150 mg as of his discharge approximately 2 weeks later, when he fully recovered physically and mentally. The patient was managed with rivaroxaban 30 mg/d for the first 2 weeks and then 20 mg/d for 3 months.
During the outpatient follow-up period of 15 months, at which point this report was prepared, the patient remained free of any further psychotic, mood, or thromboembolic episodes.
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pmc-6194638-1
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A 55-year-old previously healthy woman, without family history, native from Morocco, living in Belgium for almost two decades, presented at the ophthalmologist consultation with sudden onset bilateral painful red eyes and photophobia. No other current or previous complain was observed and her general state was preserved. She had no treatment, especially no NSAID, nor antibiotic. On eye examination, she was diagnosed with bilateral anterior uveitis, without granuloma. Her physical exam was otherwise normal. She benefited from an intravitreal injection of celestone and was put under degressive (1-month) topical corticosteroid therapy (prednisolone), in association with a cycloplegic agent. Laboratory tests revealed hemoglobin level 11 g/dl (NV 12.2–15), mean corpuscular volume 84.2 fl., creatinine level 1.37 mg/dl (NV 0.6–1.3), GFR (CKD-EPI) 43 ml/min/1.73m2 and serum potassium 3.47 mmol/l (NV 3.5–5 mmol/L). White blood cells (WBC) count showed leukocytosis to 10,830/mm3 (NV 4000–10,000) with neutrophils 7450/mm3 (NV 1600–7000) and eosinophils 630/mm3 (NV 30–600). Serum lysozyme, angiotensin convertase and HLA-B27 haplotype were negative, as were infectious serologies for syphilis, toxoplasmosis, HBV, HCV and HIV, and tuberculin skin test. No auto-immune marker (ANCA, antinuclear antibody and rheumatoid factor) was found. A urinary dipstick showed protein (2+), glucose (2+) and leucocytes (3+, 169/field), while the urine culture remained sterile. Laboratory tests, performed two years and one month before the initial ocular presentation, respectively demonstrated creatinine to 0.61 mg/dl and 1.08 mg/dl. Moreover, a fasting glycaemia of 91 mg/dl and a mild elevation of C - reactive protein (CRP) were found on the later.
The patient was addressed to our internal medicine consultation for renal evaluation. Renal involvement was confirmed (Creat. 1.14 mg/dl, GFR 54 ml/min/1.73m2), with hypouricemia (1.9 mg/dl; NV 2.4–5.7), hypophosphatemia (0.57 mmol/l; NV 0.84–1.45), normalized serum potassium and WBC count, normal albumin and CRP level of 16 mg/l (NV < 5). Serum protein electrophoresis and C3, C4 levels were unremarkable. Glycosuria (3.40 g/l; NV 0–0.05), proteinuria (Protein-Creatinine Ratio (PCR) 1.36 g/g) with mild albuminuria (ACR 380 mg/g) and elevated urine Beta-2 microglobulin (> 4 mg/l) were attested on the urine spot. There was no urinary free light chain, but hyperaminoaciduria. Excretional fraction for potassium was 23% (NV 10–20), uric acid 22% (NV < 10%), and phosphor reabsorption rate was 78% (NV: 85–95). Blood and urine tests showed renal proximal tubulopathy consistent with renal Fanconi syndrome. The chest radiography and renal doppler ultrasound were normal. A renal biopsy (Fig. .) was performed and revealed a total of 9 glomeruli (all normal, except for one sclerotic glomerulus) and severe diffuse interstitial inflammatory infiltrates with mononuclear cells, polynuclear neutrophils and eosinophils. No granuloma was identified. Foci of acute tubular necrosis and tubulitis were found. Immunofluorescence staining was negative for immunoglobulin, complement (C3d and C1q) or light chain. As the 18-FDG-PET-CT showed no focal or systemic increased uptake, we concluded to a Tubulo-Interstitial Nephritis with Uveitis (TINU) syndrome.
Soon after the diagnosis was obtained, the patient relapsed a bilateral anterior uveitis and topical steroids were restarted. Considering the severe renal involvement found on biopsy, an oral degressive-corticosteroid therapy (initial dose, methylprednisolone 48 mg/d; tapered over 8 months) was initiated. This resulted in a favorable renal outcome at six weeks (creat. 0.89 mg/dl, GFR 73 ml/min/1.73m2, no glucosuria, serum uric acid 2.4 mg/dl), but with persistent leucocyturia.
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pmc-6194641-1
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A 14-month-old female was referred to our hospital with a history of an enlarging abdominal mass noted by her parents for 3 days. Physical examination revealed an abdominal mass with clear and smooth margins extending from the right upper quadrant to the right hemipelvis. Routine blood tests were normal apart from mild anaemia and urine analysis did not show hematuria. Ultrasonography of the abdomen revealed a unilateral 10.8 × 7.2 × 9.2 cm solid tumor in the right kidney, whereas the contralateral kidney was normal. Computed tomography (CT) revealed a large lesion arising from the inferior aspect of the right kidney, occupying the right flank and extending across the midline. Enhanced CT detected duplication of IVC below the renal veins and compression and displacement of the right IVC caused by the enormous tumor (Fig. ). An additional movie file shows this in more detail [see Additional file ].
Neither intravascular extension nor invasion to adjacent organs and regional lymph nodes was detected by CT. Chest radiography was reported normal.
With the presumptive diagnosis of WT, a right-sided radical nephrectomy was performed. Final pathology was consistent with favorable histology, stromal-predominant (60%) WT. The renal vessel and IVC were tumor free. The renal hilar and para-aortic lymph nodes were also free from tumor and the final pathological stage was Stage I. According to the regimen of the National Wilms’ Tumor Study Group 5, the patient received postoperative chemotherapy with dactinomycin and vincristine. CT imaging at 3 months postoperatively showed no evidence of residual or recurrent disease. Interestingly, the right IVC played a dominant role and the left IVC seemed to disappear in postoperative enhanced CT (Fig. ). An additional movie file shows this in more detail [see Additional file ]. During the follow-up of 18 months, no local recurrence or metastasis has been observed.
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pmc-6194643-1
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This is a case of a 72-year-old Taiwanese man who was diagnosed as having metastatic adenocarcinoma of the lung complicated by malignant right pleural effusion 2 years ago. He initially presented with weight loss, worsening cough, and worsening exertional shortness of breath for 3 months prior to presentation. He had a past medical history of type 2 diabetes mellitus, which was well controlled on insulin. He was an ex-smoker of tobacco with a tobacco smoking history of one pack a day for 10 years but he quit smoking tobacco 20 years ago. He also had a family history of non-Hodgkin lymphoma in his brother and breast cancer in his niece. He is retired and lives with his wife.
On examination, he was afebrile with heart rate of 70 beats/minute and with blood pressure (BP) of 130/80 mmHg. He appeared moderately built and was not in any respiratory distress. His respiratory examination was significant for dullness over the right middle and lower chest on percussion and was associated with reduced breath sounds on auscultation. His cardiovascular, abdominal, and neurological examinations were non-contributory.
His initial computed tomography (CT) scans demonstrated a middle lobe mass in his right lung and right lung pleural effusion. A positron emission tomography (PET) scan showed an increased uptake in the middle lobe mass in his right lung, subcarinal lymph nodes, several bilateral subcentimeter pulmonary nodules, and diffuse osseous metastasis. There was no evidence of brain metastasis as evidenced by magnetic resonance imaging (MRI) of his brain. He then had thoracentesis and pleural biopsy with the placement of a pleural catheter. The pleural biopsy was consistent with adenocarcinoma with an acinar pattern. Immunohistochemistry of the tumor cells was positive for cytokeratin (CK) 7, thyroid transcription factor 1 (TTF-1), and negative for CK20. A fluorescence in situ hybridization (FISH) showed evidence of ALK mutation (33% of cells positive for rearrangement). His final diagnosis was stage IV ALK + adenocarcinoma of the lung with metastasis to pleura, mediastinum, and bones. Before the information of ALK positivity was obtained, he was started on combination chemotherapy consisting of carboplatin, Alimta (pemetrexed), and Avastin (bevacizumab) of which he successfully completed five cycles. He was followed up regularly in the clinic every 4 weeks. He tolerated the chemotherapy and had a good response with 30% reduction in the lung mass size. He was later started on crizotinib 250 mg twice per day and had a significant response with improved tumor burden in his metastatic sites. He followed up in the clinic every 4 weeks initially for 6 months and then every 8 weeks for 1 year. During his follow-up visits, he remained stable with no evidence of disease progression. He remained on crizotinib for over a year and tolerated it well. During one of the follow-up clinic visits at around 18 months after diagnosis, an MRI scan of his brain was arranged due to a new symptom of headache; it showed numerous brain metastases which was consistent with progression of his disease. A decision was made to stop crizotinib and to start alectinib 600 mg twice daily coupled with cranial radiation.
Within 5 weeks of starting alectinib, he developed ARF with his creatinine (Cr) increasing up to 8.16 mg/dL and blood urea nitrogen (BUN) to 113 mg/dl. He was anuric at presentation and his laboratory tests were consistent with hyperkalemia and acidosis with a potassium level of 7.1 mEq/L and bicarbonate (HCO3) of < 9 mmol/L. His renal workup revealed BUN/Cr ratio of 13, fractional excretion of sodium (FENa) of 16%, urine sodium of > 83 mEq/L, and urine osmolality of 334 mOsm/kg. His renal ultrasound did not show any evidence for obstruction (hydronephrosis). Table illustrates the laboratory values and Fig. illustrates the timeline of our patient’s renal functions.
Since he was refractory to medical treatment, he required continuous venovenous hemodialysis (CVVH) due to the electrolyte imbalance. Alectinib was held on admission and dialysis was continued for 2 days until the electrolyte imbalance was corrected. Renal biopsy could not be performed as our patient refused.
His renal functions slowly recovered and Cr improved to 1.75 mg/dL within 2 days. He was re-challenged with alectinib at the same dose 24 hours after renal recovery. However, the medication had to be stopped again as his Cr started to worsen and rose to 3.6 mg/dL within 2 days of restarting alectinib. Currently, he is being treated with ceritinib, and his renal status has been stable with Cr levels ranging between 2 and 3 mg/dL. He also has no progression of his metastatic disease as evidenced by his recent imaging.
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pmc-6194693-1
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A 58-year-old Japanese woman was admitted to our hospital by ambulance because of a 1-week history of malaise, lumbago, and fever of unknown origin. She had no relevant medical history and no family history. She was a nonsmoker, but she had drunk about 60 to 80 g of alcohol per day for 30 years. Liver dysfunction had been noted for the past 10 years.
On admission, her height was 158 cm, weight 56.2 kg, and body temperature 39.5 °C. Her blood pressure was 101/60 mmHg. Her heart rate was 106 beats per minute. A physical examination showed no major abnormalities. She was alert but short of breath on exertion, with an arterial blood oxygen saturation of 94%, partial oxygen pressure of 72.0 mmHg, and partial carbon dioxide pressure of 27.2 mmHg. A chest radiograph showed no obvious signs suggesting pneumonia or pulmonary congestion. Electrocardiography showed sinus tachycardia and no other abnormalities. Plain computed tomography of the neck, chest, and abdomen and ultrasound of the abdomen revealed no significant abnormalities except for fatty change of the liver. Laboratory tests showed an elevated white blood cell count; elevated levels of serum liver enzymes, blood urea nitrogen, creatinine, uric acid, C-reactive protein (CRP), and serum brain natriuretic peptide; hypoproteinemia; and hypokalemia (Table ). Serum rheumatoid factor was negative. Urinalysis was positive for ketone bodies, but the urinary sediment showed no abnormalities. Cultures of blood, urine, and sputum were carried out on admission. Intravenous administration of sulbactam/ampicillin (SBT/ABPC) (9 g/day) was begun from the day of hospitalization.
On day 2, the patient remained febrile. The sputum culture showed no significant growth of pathogenic bacteria, and the urine culture was sterile. However, gram-negative rods were detected in the blood culture. Subsequent echocardiography revealed two vegetations, one of which was attached to the anterior leaflet of the MV and was approximately 4 × 1 mm in size (Fig. ). The other was attached to the chorda tendinea adjacent to the posterior papillary muscle, and its size was larger (10 × 2 mm) than that of the MV vegetation (Fig. ). Based on these findings, combined antibiotics including SBT/ABPC (9 g/day) and gentamycin (GM) (80 mg/day) were administered on day 2. Repeated blood cultures were also performed on days 2 and 3, and all culture sets were positive for gram-negative rods, which were proven to be pansensitive E. coli on day 6. Based on these findings, the patient was diagnosed with IE due to E. coli in accordance with the modified Duke criteria []. An ophthalmologist and dermatologist also examined her on day 6, but they observed no remarkable findings associated with IE. Contrast-enhanced computed tomography of the chest and abdomen on day 7 showed no remarkable findings; magnetic resonance imaging (MRI) and magnetic resonance angiography of the brain on day 8 also showed no abnormalities.
After antibiotic medication including SBT/ABPC and GM, the patient’s general condition improved. Her body temperature normalized on day 5, and her white blood cell count returned to a normal level (8600/mm3); her CRP level significantly decreased (5.09 mg/dL) on day 6. Blood culture analysis on day 7 and thereafter revealed no bacterial growth, but her CRP level remained mildly elevated (about 2.0 mg/dL). Echocardiography on day 14 showed a decrease in the size of the vegetations; those attached to the MV and chorda tendinea were 2 × 1 and 5 × 1 mm, respectively. However, the patient developed severe lumbago on day 20. Her white blood cell count was normal (5900/mm3), but her CRP level had increased to 3.1 mg/dL. MRI of the lumbar spine on day 21 revealed purulent spondylitis lesions in the L1 and L2 lumbar vertebrae. Intravenous meropenem (6 g/day) was substituted for SBT/ABPC and GM on day 21 despite the sterile blood culture. The patient’s clinical course was good thereafter; her lumbago improved. Transthoracic echocardiography on day 35 revealed complete resolution of the vegetations. On day 54, her CRP level decreased to 0.34 mg/dL. Administration of meropenem was terminated, and she was discharged from our hospital on day 56. After discharge, oral levofloxacin (500 mg/day) was administered for 2 months in accordance with the suggestions of orthopedic surgeons. Her CRP level normalized after 2 months. Both upper endoscopy and colonoscopy performed 3 months after discharge showed no abnormalities. MRI findings of the lumbar spine normalized after 7 months. She also stopped drinking alcohol for 12 months and remained well during that time.
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pmc-6194699-1
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A 66-year old woman of Turkish descent attended our clinic in January 2015. She was asymptomatic at a routine follow-up 20 months after kidney transplantation and had an unremarkable physical examination. Of note, her creatinine had risen from 1.8 to 2.6 mg/dl since April 2014 and the urinary protein-creatinine-ratio had increased from 200 to 440 mg/g. Microhaematuria was absent at first, but became evident on repeat testing within 1 week (20 red cells per high-power field, no red cell casts).
Her background medical history consisted of coronary artery disease, hypertension, asymptomatic sinusitis and obesity. She had no known history of connective tissue or autoimmune disease. She had reached ESRF secondary to autosomal dominant polycystic kidney disease at the age of 58 years. After 7 years of haemodialysis, she received a deceased-donor kidney transplant without induction immunosuppression in May 2013 (baseline characteristics and human leucocyte antigen (HLA) genotyping of recipient and donor are shown in Table ). An episode of asymptomatic cytomegalovirus (CMV) reactivation (1160 CMV copies / ml) 8 months after transplantation responded to valganciclovir and reduction of mycophenolate dose. At the index presentation, medications had been unchanged for more than 3 months. These were prednisolone 5 mg OD, cyclosporine A 50 mg BD, pantoprazole 20 mg OD, metoprolol 47.5 mg BD, doxazosin 4 mg BD, aspirin 100 mg OD, simvastatin 20 mg OD, allopurinol 150 mg OD and calcitriol 0.25 μg OD.
A biopsy of the kidney transplant in response to the unexplained rise in creatinine showed eleven glomeruli, three of which were globally sclerotic. Unexpectedly, three of the remaining glomeruli demonstrated extracapillary proliferative changes, with crescent formation and necrosis in two (Fig. ). Interstitial inflammation with eosinophilic cells and borderline changes suspicious for acute cellular rejection (Banff 3) were also seen. The lack of deposition of complement or immunoglobulins indicated a histological diagnosis of pauci-immune crescentic glomerulonephritis.
Autoimmune serology tested strongly positive for anti-neutrophil cytoplasmic antibodies (ANCA) with a typical cytoplasmic immunofluorescence pattern and specificity to proteinase 3 (PR3) (Euroimmun, Germany). ANCA specific to myeloperoxidase (MPO), anti-glomerular basement membrane antibodies, anti-nuclear antibodies and cryoglobulins were negative; complement and alpha-1-antitrypsin levels were normal. Donor-specific HLA antibodies were tested at time of biopsy and were negative. Retrospective analyses of frozen serum samples from 49 days prior and 36, 63, 96, 226 and 335 days post-transplantation were all negative for PR3-ANCA or MPO-ANCA. Lung involvement could be excluded with CT scan. A clinical review for vasculitis-typical features revealed that nasal crusting and bloody nasal discharge, the only extrarenal manifestations, had developed several months before the transplant biopsy. All of these findings supported the diagnosis of AAV and its specific subtype granulomatosis with polyangiitis.
We commenced treatment with intravenous prednisolone 250 mg for 3 days followed by rituximab 1 g and oral prednisolone 50 mg/day. Despite this, serum creatinine rose to 4.1 mg/dl over the next 2 weeks, prompting a second transplant biopsy 19 days after the first. The repeat biopsy contained 14 glomeruli, four of which were globally sclerotic. Three of the remaining glomeruli showed extracapillary proliferative changes and one of these exhibited necrosis. Minor features of ischaemia and mild interstitial inflammation were present, but no signs of rejection. Immunohistochemistry and electron microscopy remained consistent with pauci-immune glomerulonephritis.
In view of the refractory disease course, we added seven sessions of plasma exchange. This was followed by a second administration of rituximab 1 g, a tapering course of oral prednisolone and antibiotic prophylaxis with co-trimoxazole. After 2 weeks, serum creatinine declined to 2.6 mg/dl, suggesting a partial recovery of renal graft function. The patient’s clinical course is summarised in Fig. .
A series of complications ensued. The patient developed corticosteroid-related diabetes mellitus, pneumonia with neutropenia and CMV reactivation in serum (586 copies / ml), requiring antimicrobial and antiviral therapy. Interventional occlusion of an arteriovenous fistula that had emerged after the first biopsy did not avert the rising trend in creatinine. A second infection episode occurred, fluid retention became problematic and creatinine rose to 7 mg/dl. Regular haemodialysis was recommenced from May 2015 onwards, 24 months after transplantation and 4 months after the initial presentation with rising creatinine and proteinuria. Transplant related immunosuppressive therapy with cyclosporine and mycophenolate was tapered and consecutively stopped while low-dose therapy with prednisolone for treatment of AAV was continued. The transplanted kidney was resected in September 2015 due to the new development of donor-specific HLA antibodies (anti-HLA-A2) and persistent haematuria. Histological examination found chronic and active antibody-mediated and cellular rejection, but no extracapillary proliferation. Rituximab was continued for maintenance therapy. PR3-ANCA remained positive, but declined steadily. There has been no further clinical vasculitis activity during follow-up for 2 years.
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pmc-6194714-1
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The patient was a 23-month-old boy who was referred for cytogenetic studies because of speech delay and mental retardation. He was born at 38 weeks gestation following an unremarkable pregnancy by Caesarean section. His birth weight was 3.40 kg (<50th centile), and birth length was 52 cm (>75th centile). At birth, he had an umbilical hernia, which healed at 3 months of age.
The patient could sit at 8 months, and took his first steps at 18 months. At 23 months, his height was 90 cm (<75th centile), and his weight was 13 kg (<75th centile). He cannot speak meaningful words and walked with instability and large strides. Medical examination revealed developmental delay, sensory integration dysfunction, moderate MR, and reduced cognitive ability. Additional physical features included hypotonia, a moon face, midface hypoplasia, deep-set eyes, epicanthal folds, a wide nasal bridge, a flat nose, a protrusible mouth, short neck, and a longer fourth toe of the right foot. No significant defects such as cleft lip/palate, ears, heart, lung or genitourinary system were noted.
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pmc-6194912-1
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A previously healthy Moroccan man in his late 40s was admitted to an internal medicine ward of a tertiary hospital in Florence, Italy, in mid-August 2018, with a 3-day history of high fever (> 38.5°C), headache, and mild cough. At physical examination, jaundice and splenomegaly were observed. Blood tests showed thrombocytopenia, haemolytic anaemia, and increased inflammatory markers (). A haematological disease was suspected, while malaria was initially not considered, since the patient declared to have not recently visited any endemic area. On Day 4 after admission, investigation for malaria was requested following an infectious diseases consultation. Thin blood smears revealed the presence of P. falciparum trophozoites with a parasitaemia of 0.5%. PCR confirmed P. falciparum mono-infection. The patient was referred to the Infectious and Tropical Diseases Unit with the diagnosis of severe malaria (haemoglobin (Hb) < 7 g/dL and parasitaemia > 0.2% []), and intravenous artesunate was administered for 2 days, followed by oral dihydroartemisin-piperaquine for 3 days. Two units of packed red blood cells were transfused. The patient's conditions improved and he was discharged a few days later. The case was notified to public health authorities (malaria is a mandatory notifiable disease in Italy) and microscopically confirmed by the National Institute of Health, Rome, Italy [].
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pmc-6194918-1
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A 61-year-old Chinese female with no known past medical history presented to the hospital with altered mental status for 1 week with associated fever, neck pain, nausea, and vomiting. It was not possible to obtain history from her due to her altered mental status; her family denied complaints of abdominal pain, headache, visual changes, focal weakness, chest pain, or dyspnea. She had been waking up in the middle of the night to cook meals and clean her house, and was intermittently somnolent. The patient did not smoke, drink alcohol, or use illicit drugs. She was born in China and immigrated to the United States, where she resided for the past 30 years with no foreign travel during that time. She had not seen a physician in her adult life and took no medications. Given her altered mental status and concern about the stability of her airway, she was intubated in the emergency department.
On admission to the intensive care unit, the patient’s vital signs were as follows: temperature 36.5°C, heart rate 90 beats/min, respiratory rate 22 breaths/min, blood pressure 108/61 mm Hg, and oxygen saturation of 100% on an FiO2 (fraction of inspired oxygen) of 40%. Physical examination demonstrated a positive Brudzinski sign and neck stiffness, even while sedated. Pupils were equal round and reactive to light, and she responded to painful stimuli. Her lungs were clear to auscultation bilaterally, and cardiac examination was unremarkable without a murmur. Her abdominal examination was normal with no hepatomegaly or ascites.
Admission laboratory data demonstrated white blood cell count of 19 900/mm3 (81% neutrophils), hemoglobin 11.8 g/dL, platelet count 170 000/µL, creatinine 0.5 mg/dL, bilirubin 0.6 mg/dL, aspartate transaminase 49 IU/L, alanine transaminase 81 IU/L, alkaline phosphatase 142 IU/L, and albumin 1.9 g/dL. Electrolytes were within normal limits. C-reactive protein was 4.19 mg/dL, and erythrocyte sedimentation rate was >100 mm/h. She had mild hyperglycemia on admission, with glucose 132 mg/dL and hemoglobin A1c of 6.4%.
Magnetic resonance imaging of the brain demonstrated diffuse leptomeningeal enhancement most conspicuous along the bilateral temporal lobes and insula, subarachnoid space of the basal cisterns, and the ventricular system, and proteinaceous material and pus were visualized within the subarachnoid space and bilateral lateral ventricles (). Neurosurgery placed an external ventricular device to help drain cerebrospinal fluid (CSF). Lumbar puncture yielded clear CSF with an opening pressure of 22 cm H2O, a white blood cell count of 5051/mm3 (neutrophils 87%), protein 803 mg/dL, and a glucose 4 mg/dL. CSF culture was positive for K pneumoniae.
Magnetic resonance imaging of the abdomen demonstrated a complex multiloculated cystic space occupying lesion 6.3 × 4.6 cm with a small amount of surrounding edema and no intrahepatic or extrahepatic biliary dilatation (). Percutaneous aspiration yielded 25 cc of thick, purulent fluid, which was positive for K pneumoniae; a catheter was placed into the hepatic abscess. Blood cultures were positive for K pneumoniae.
She was initially treated with meropenem and intrathecal gentamicin. She subsequently developed seizures. With concern of lowered seizure threshold from meropenem, this was changed to cefepime. Ciprofloxacin was added as she developed worsened mental status, and repeat central nervous system (CNS) imaging revealed increasing leptomeningeal enhancement and fluid within the occipital horns, consistent with worsening meningitis and ventriculitis. Her external ventricular devices repeatedly clogged and a total of 6 external ventricular drains were placed. Thirty days after admission, she developed diabetes insipidus, uncal herniation, and progressed to brain death.
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pmc-6194919-1
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A 56-year-old Caucasian male with a history of non–muscle invasive UC, hypertension, and type 2 diabetes mellitus presented to an oral surgeon with 3 weeks of swelling and pain in his right anterior mandible. Up to that point, his mandibular lesion had been unresponsive to amoxicillin or cephalexin. A cone beam radiograph obtained at the time of presentation showed a radiolucent lesion of the mandible concerning for tumor. An incisional biopsy was performed, and a sample was submitted to our institution for pathologic evaluation. Microscopic examination of hematoxylin and eosin stained sections showed UC, which was confirmed by a positive GATA-3 immunostain, consistent with metastatic UC ().
The patient was initially diagnosed with UC 4.5 years prior during evaluation for gross hematuria. Initial cystoscopy showed a 3-cm anterior bladder wall tumor near the bladder neck, a 1- to 2-cm left anterior wall tumor, and a 1-cm right anterior wall tumor. Subsequent TURBT was performed with collected specimens demonstrating noninvasive high-grade papillary UC (TaHG). Muscularis propria was present in all specimens. Given the multiple foci of TaHG lesions, the patient was classified as high-risk. Following TURBT, the patient underwent induction with intravesical BCG and interferon (IFN). Postinduction TURBT was negative for evidence of tumor and both cytology, and fluorescent in situ hybridization (FISH) studies were additionally negative at that time. The patient was scheduled to receive 3 maintenance cycles of intravesical BCG/IFN; however, therapy was discontinued after the second cycle due to development of scrotal swelling and fever. Throughout BCG/IFN maintenance the patient underwent surveillance cystoscopy with cytology and FISH analysis every 3 months for 2 years before spacing surveillance to 6 months. All studies (cystoscopy, cytology, and FISH) performed during surveillance were negative, with no evidence of local recurrence. Additionally, the patient underwent a computed tomography (CT) Urogram at 18 months after his initial TURBT, which was negative for evidence of tumor.
After metastatic UC was identified in the mandibular biopsy, the patient underwent a fluorodexoyglucose positron emission tomography (PET)-CT scan that showed a destructive hypermetabolic soft tissue lesion at the mandibular symphysis without evidence of lymphadenopathy in the neck and bilateral hypermetabolic lung masses concerning for metastases (). Notably, no hypermetabolic lesions were noted in the abdomen or pelvis. The patient was presented at our institution’s urology and genitourinary oncology tumor board and was subsequently referred to medical oncology and radiation oncology for management. At present, the patient is undergoing palliative radiotherapy to the mandible and is scheduled to begin gemcitabine/cisplatin systemic chemotherapy.
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pmc-6195010-1
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An 88-year-old male was admitted to the medical floor with 2-week history of abdominal distention and bloating. The patient reported associated decreased appetite, early satiety, and generalized weakness. He was actively working as a part-time barber for the past 55 years. Prior to that, he worked at an insulation production factory between the ages of 23 and 25 years with presumed asbestos exposure. Additional exposure history significant for 10 pack-year smoking (1 pack × 10 years) and significant passive smoking exposure. Physical examination was notable for distended abdomen with mild tenderness to deep palpation in all quadrants. There was no rebound tenderness or guarding. Fluid wave test was positive, and he had lower extremity edema. Initial laboratory workup was unremarkable, except for low serum albumin (). Computed tomography (CT) scan of the abdomen/pelvis with contrast showed diffuse omental, peritoneal, and mesenteric nodularity with moderate to large ascites (). Given these new findings, workup was directed to look for the primary malignancy. CT chest with contrast was done, which was negative for primary lung malignancy. However, CT chest with contrast showed bilateral pleural plaques indicating prior asbestos exposure. Esophagogastroduodenoscopy and colonoscopy were unremarkable. Tumor markers CEA, PSA, CA 19-9, and AFP were also within normal limits. Therapeutic and diagnostic paracentesis were done, which yielded 2.5 liters of blood-tinged fluid. Ascitic fluid analysis revealed the values shown in .
Serum-ascites albumin gradient was calculated at <0.7, indicating ascites not associated with portal hypertension. Given the findings of the fluid analysis and CT abdomen, the patient underwent ultrasound-guided omental biopsy. Tumor cells were positive for calretinin, WT-1, CK5/6, and mesothelia () confirming the diagnosis of MPM, epithelioid subtype. Given the patient’s advanced age and his medical comorbidities (coronary artery disease and hypertension), the patient was deemed not a candidate for cytoreductive surgery (CRS) or platinum-based chemotherapy. With the poor prognosis of MPM in mind, the patient opted not to pursue further treatment and decided to go home with home hospice. Palliative peritoneal catheter was placed, and the patient was discharged home with home hospice care.
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pmc-6195681-1
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The patient was a 46-year-old man who presented with a history of abdominal distension and dyspepsia in September 2017. The complete blood picture showed white blood cell count 4.53 × 109 with neutrophils 47%, lymphocytes 44%; hemoglobin, 12.3 g/dl; hematocrit36.5%; and platelet count 109 × 109/ L. Flow cytometric analysis performed on peripheral blood specimens showed CD3+ cells 60.33%, CD3 + CD4+ cells 24.97%,CD3 + CD8+ cells 33.86%,NK cells 26.07%,CIK cells 18.51%,B cells 8.23%. Ultrasound images showed that the spleen is slightly enlarged with no hepatomegaly. In the year 2012, Endoscopic examinations found ileal mucosal inflammation. In 2015, endoscopic examination showed patchy erythema of the gastric fundus, and two polyps (2-3 mm) in the ascending colon and rectum. In 2017, endoscopic examination revealed rough hyperemic gastric antrum and body mucosa. Eight wide pedicle (2-3 mm) polyps were seen in the ileocecal junction and ascending colon. The sigmoid colorectal mucosa was congested and there were no ulcers or masses (Fig. ). The patient was not given any chemotherapy and was followed up closely with no evidence of disease progression. As to date, the patient remained asymptomatic without any treatment.
The following GIT biopsy and bone marrow specimens were available for review: ileum (2012), stomach (2015), colon (2015), stomach (2017), colon (2017), bone marrow (2017). All biopsy specimens showed diffuse or patchy infiltrates of predominantly small sized lymphocytes in the lamina propria with focal infiltration through the muscularis mucosae. The lymphocytes are small and monomorphic with round or angulated nucleus exhibiting fine chromatin, ambiguous nucleoli and scant to moderate pale cytoplasm (Fig. ). The glands were displaced by the lymphoid infiltrate without being invaded or destroyed. There is no necrosis, angioinvasion or angiodestruction. Scattered plasma cells were seen in the superficial lamina propria. Mitotic activity was low in all specimens.
Repeated immunohistochemical staining showed that the lymphoid cells were positive for CD3, CD20, CD5, CD43, CD7, CD2, TIA1 but negative for CD4, CD8, PAX5, CD56, cyclinD1, graB, βF1. In addition, the T-cell infiltrate showed slightly dimmer expression of CD20 than the background normal B-cells. Ki-67(MIB1) proliferative index was less than 10% (Fig. ). In situ hybridization for EBER was negative.
Multiple polymerase chain reactions (PCR) for TCRß, TCRδ, TCRγ and IgH, IgK, IgL gene rearrangement were performed on biopsies from the stomach (2017) and the colon (2017). The same clonal TCRγ gene rearrangement was found though TCRß and TCRδ were germline, confirming clonal T-cell proliferation. IgH, IgK, IgL gene rearrangement was not detected (Fig. ).
Bone marrow biopsy obtained in 2017 showed small patchy and interstitial lymphocytic infiltrates composed of similar small round lymphocytes representing less than 20% of the medullary spaces in the biopsy. Immunohistochemistry showed that the cells were positive for CD3, CD20, and negative for CD56, PAX5.
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pmc-6195710-1
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A 43-yr-old, 66 kg, 175 cm man was to undergo gastrectomy for a tumor in the stomach. He had no history of hypertension, myocardial infarction,or angina pectoris,but with a smoking history(10 packs year).His physical examination was normal. Preoperative resting electrocardiogram (ECG) (Fig. )and echocardiogram(UCG) were within normal limits. Laboratory data revealed no abnormalities.
No premedication was given. After the patient,s arrival in the operating room, intravenous access was established. Lead II and V5 of the ECG were monitored. Blood pressure (BP) was 128/70 mmHg and heart rate(HR) 75 beats/min. An ultrasound-guided subcostal TAP block was performed bilaterally []. Each hemi abdomen was injected with 20 ml 0.3% ropivacaine to give a dual block from T6-T9. TAP block was uneventful without heart rate and blood pressure variations. After 30 min, general anesthesia was induced, then it was maintained with sevoflurane inhalation, target controlled infusion (TCI) remifentanil and given sufentanil and cisatracurium intermittently. The patient was mechanically ventilated with a tidal volume of 500 ml and respiratory rate of 10 breaths/min to maintain PetCO2 at 35–40 mmHg under end-tidal CO2 monitoring. Arterial BP was continuously monitored via a left radial artery catheter.
Two hours after start of the operation, when the surgeons were dissecting para gastric lymph node, ST segment elevation in lead II was noted (Fig. ) and lead V5 showed no abnormalities. The change recovered abruptly without treatment 30 s later. When it happened, SpO2 was 100%, end-tidal sevoflurane concentration was 1.3% and no obvious hemorrhage. Except for this, the patient,s course during 4 h of operation was uneventful: BP was about 100/70 mmHg, HR about 70 beats/min, body temperature about 36.5 °C and estimated blood loss was less than 300 ml. Four hours after start of the operation, the arterial BP was 88/55 mmHg and aramine 0.4 mg was given intravenously. The BP increased to 110/65 mmHg without HR change. Approximately 5 min later, the ECG showed premature ventricular contractions and a marked ST segment elevation again (Fig. ). Ventricular tachycardia and fibrillation were subsequently noticed with BP decreased to 32/14 mmHg, and electric defibrillation was initiated with repeated infusions of epinephrin. Within approximately 2 min, the ECG returned to sinus rhythm and BP gradually to normal. The patient remained hemodynamically stable for the remainder of the operation. Following the operation, he was transferred to the cardiac care unit (CCU) in our hospital. Serial ECGs and cardiac enzyme studies showed no abnormalities, thus ruling out myocardial infarction and CAS was diagnosed. The patient suffered no further cardiac attacks during his hospital stay. Consent was obtained from the patient to publish this case report.
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pmc-6195733-1
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A 38-year-old female from Guangdong province in China was admitted to Zhujiang Hospital, Southern Medical University in June 2016. At the age of 30, she developed progressive poor gait balance so that she frequently fell down when walking. At that time, she went to a local hospital for treatment, but diagnosis was not established. She was transferred to the Second Hospital Affiliated to Guangzhou Medical Hospital for hospitalization on December in 2010, where she was clinically diagnosed as cerebellar atrophy, Type 2 Diabetes and hyperlipemia. However, the treatments prescribed did not prevent disease worsening. In 2015, she presented a slowly progressing retardation. Within the year 2016, she began to suffer from bad-response, psychiatric manifestations, bilateral hearing loss and intermittent convulsion in her upper limb during sleeping, especially the right upper limb. With such complex symptoms, she was referred to our hospital. Her parents were not consanguinity, and no neurological disorders were found in her family members except herself.
Physical examination showed that she had mild mental retardation, apathy and spoke few words. Cranial nerves were normal except for symmetric bilateral sensory hearing loss. She did not cooperate with the neurological examination and sensibility could not be tested. Her muscle strength of bilateral upper limbs was normal but was decreased in lower limbs. Muscle tone was normal, but her right upper limb had abnormal involuntary movement. The patient had no pyramidal signs. Cerebellar function examination showed mild abnormalities on finger- to- nose, heel- to-knee and rapidly alternating pronation and supination of hands. Romberg test was negative.
Electrocardiogram investigation demonstrated sinus bradycardia (44/min on average). Nerve conduction studies revealed significant deceleration of motor conduction velocity in the right peroneal nerve (25.9 m/s), right median nerve (38.4 m/s), left ulnar nerve (45.5 m/s), right ulnar nerve (35.6 m/s) and the prolongation of F wave latency. The sensory nerve action potential could not be evoked in the bilateral peroneal nerve, sural nerve, and left median ulnar nerves. Electroencephalogram demonstrated mild to moderate abnormality and showed basic rhythms as 7.2–10 Hz and 20–40 μV slow alpha activities with low amplitude and irregular wave. Few 14–25 Hz and 20–30 μV beta waves sporadically emerged and more 4–7 Hz and 20–40 μV theta waves presented sporadically or in short-term in each lead. Visual evoked potential showed the extending of bilateral latency of P100 (Left = 101.1 mS, right = 107.0 mS) and decreased amplitude (Left = 3.24 μV, right = 1.30 μV). Brainstem auditory evoked potential showed bilateral disappearance of III-I, V-I and V-III IPL. Brain MRI revealed diffuse cerebral and cerebellar atrophy (Fig. ).
Exome sequencing [] (as published) performed in AmCare Genomics Lab revealed a novel heterozygous missense variant, c 1618 T > A (p. Y540N), in exon 20 of the DNMT1 (Fig. ; Additional file ).
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pmc-6195746-1
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A 51-year-old black woman with an 18-pack-year smoking history presented to our institution with a 3-month history of a progressively productive cough unresponsive to antibiotics. In addition, she had dyspnea on exertion and a 25-pound weight loss. Her past medical history included a duodenal ulcer resulting in a perforation which required exploratory laparotomy 2 years prior to presentation. Other history included subarachnoid hemorrhage requiring craniotomy with hematoma evacuation roughly 20 years prior to presentation, as well as hypertension. Her family history included her mother being diagnosed with ovarian cancer at the age of 54. The patient is married and worked full-time at the front desk for the past 30 years for a shipping company. She reported alcohol intake of two drinks per occasion twice weekly. She denied the use of any recreational drugs. She denied any environmental exposures. Medications that the patient was receiving at the time of diagnosis included amlodipine and albuterol.
The patient underwent computed tomography (CT) of the chest, which revealed a 5.3 × 6-cm right hilar mass that was occluding the right upper lobe bronchus with narrowing of the SVC. The SVC remained radiographically patent (Fig. ). The patient’s vital signs included afebrile temperature of 37.0 °C, cardiac pulse of 100 beats per minute, and oxygen saturation of 96% on room air. Her physical examination at that time was without any clinical signs of venous congestion. She had no facial plethora and had flat neck veins and no signs of jugular vein distention. She had decreased breath sounds in the right upper and middle lung fields. The skin of the neck and breast was without any pitting or edema. Neurologically, the patient was fully functional with cranial nerves II–XII intact and 5/5 strength in the upper and lower extremities bilaterally. All laboratory test results, including complete blood count and comprehensive metabolic panel, were within normal limits.
Two weeks after the patient’s initial presentation, she was found to have bilateral distended venous jugular veins, with no facial, neck, or breast fullness, which was self-limiting and resolving prior to chemoradiation. She eventually underwent an endobronchial ultrasound with fine-needle aspiration of the right hilar mass along with the contralateral mediastinal station 4L lymph node demonstrating poorly differentiated NSCLC adenocarcinoma in both sites. She then underwent brain magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT (Fig. ), which revealed no evidence of metastatic disease. She was diagnosed with T2bN3M0 stage IIIB lung adenocarcinoma according to American Joint Committee on Cancer 8th edition staging guidelines.
The patient proceeded with expedited radiation planning and treatment, given her radiographic evidence of extrinsic SVC narrowing and physical examination findings of mild and self-limiting jugular venous distention. She received a definitive radiation dose of 60 Gy in 30 fractions concurrent with chemotherapy (cisplatin and etoposide). The patient was simulated in the supine position in a whole-body Vac-Lok ™ (CIVCO Radiotherapy, Orange City, IA, USA) with arms above her head. A four-dimensional (4D) CT simulation was performed using a Philips Ingenuity CT simulation scanner (Philips, Cleveland, OH, USA) to acquire images for treatment planning and assessment of internal target motion. Treatment planning was performed using an Eclipse® treatment planning system (Varian Medical Systems, Pao Alto, CA, USA), and treatment was delivered using a TrueBeam® radiotherapy system (Varian Medical Systems) with two volumetric modulated arc therapy arcs using 6-MV photons. Gross tumor volume (GTV) was contoured on 4D CT images in different phases of the respiratory cycle. An internal target volume was created by the summation of GTV volumes of the different respiratory phases. A 5-mm expansion was used to create the clinical target volume and planning target volume (PTV), respectively. Ninety-five percent of the PTV received at least 57 Gy or 95% of the prescribed dose (Fig. ). Cycle 1 of cisplatin (50 mg/m2 on days 1, 8, 29, and 36) plus etoposide (50 mg/m2 daily on days 1 to 5 and days 29 to 33) started 2 weeks after initiation of radiation therapy. One additional cycle was given after completion of radiation for a total of two cycles of chemotherapy received. The patient did experience some breast swelling and pain that was seen with day 10 of chemotherapy. The event was suspected to be a consequence of the excess intravenous fluids (3 L) coadministered with each infusion of cisplatin. This event was in the setting of the previous stenosis of the SVC resulting from extrinsic compression from the patient’s large right hilar mass. This swelling resolved within 1 week without intervention. The patient also developed esophagitis requiring temporary gastric tube placement necessitating a 5-day hospitalization.
The patient returned to the radiation oncology department for a 3-month posttreatment follow-up visit, for which imaging was ordered. The patient reported that for the past 2 weeks she had developed swelling and pain in her right breast and right supraclavicular region, which were new for her. She also complained of worsening dyspnea on exertion, a 16-pound weight gain over the past 3 months, and intermittent headaches. She denied any facial fullness, orthopnea, or dysphagia. Examination revealed that her vital signs were within normal limits; however, she had obvious compressible swelling of the right supraclavicular region and fullness within the right breast. Chest CT performed 2 days prior to the follow-up visit revealed a remarkable reduction in size by approximately 50% of the treated right hilar mass (Fig. ). However, the SVC was significantly narrowed to completely occluded radiographically, despite being narrowed but patent before treatment. The patient was sent to the emergency department for further evaluation and management. Interventional radiology was consulted, and it was concluded that the patient’s SVC syndrome was likely chronic based on the presence of significant collaterals. No acute intervention was recommended, and she was discharged to home uneventfully.
The patient did have initial radiographic evidence of stenosis of the SVC; however, her initial stenosis did not produce SVC syndrome. The patient did respond very well to treatment, because she had marked reduction of the tumor volume and decrease in the extent of extrinsic compression on the SVC. It was peculiar that she developed SVC syndrome despite her significant treatment response.
We also contemplated intrinsic etiologies for SVC syndrome, including thrombus formation, but this consideration was not confirmed on radiographs. Interventional radiology was consulted and had reviewed her films and did not think thrombus was a likely scenario. There was a concern for recurrent or persistent microscopic disease within the region of the SVC, but there was no fludeoxyglucose avidity in the region on posttreatment PET (Fig. ). The development of an adequate collateral circulation system did indicate the chronicity of venous congestion. The differential diagnosis also included the possibility that the continued stenosis of the SVC was a direct effect of treatment (chemoradiation) because the SVC resided within the PTV receiving the full radiation dose. The SVC was contoured, and dosimetric parameters were as follows: Minimum dose to SVC was 59.74 Gy with maximum dose to SVC 62.36 Gy, and 95% of the SVC received at least 60.35 Gy (Fig. ).
The patient was presented at the multidisciplinary thoracic oncology tumor board, and observation was recommended on the basis of absence of tumor progression and presence of an adequate collateral venous system. Her supraclavicular and breast swelling was self-limited, resolving within 2 weeks after her presentation. Six months after completion of radiation therapy, she underwent PET/CT indicating recurrent thoracic disease and had a fine-needle aspiration biopsy confirming metastatic, poorly differentiated adenocarcinoma in a station 4R lymph node. She was placed on the PD-1 (programmed cell death protein 1) inhibitor nivolumab. Brain MRI was performed for workup, revealing two ring-enhancing lesions in the left frontal and right cerebellum, the largest of which was 2.2 × 1.8-cm in the left frontal lobe. Gamma Knife® (Elekta, Stockholm, Sweden) stereotactic radiosurgery was performed on the two lesions. One year after completion of definitive thoracic radiotherapy, the patient was found to have a new metastatic left parieto-occipital brain lesion that was being worked up at the time of this report. She has not had redevelopment of SVC syndrome.
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pmc-6195874-1
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A 52-year-old man with a history of appendectomy presented to his family physician suffering periumbilical cramping pain with sudden onset. He received oral medication, but the symptoms persisted.
One week later, he was referred to Fukui Katsuyama General Hospital, and his symptoms continued to persist. He received a liquid-only diet over this period without vomiting. On physical examination, he showed a pulse of 108 beats/minute, a blood pressure of 140/80 mmHg, and a body temperature of 37.2 °C. Anemia, jaundice, edema, and malnutrition were not found. Abdominal distention with mild tenderness on palpation was noted. No external hernia was present. Laboratory data showed only a mild elevation of the white blood cell (WBC) count (10.2 × 103/μL) without any elevation in the C-reactive protein (CRP) level (0.12 mg/dL).
MDCT with dynamic enhanced study revealed intestinal ileus, and two closely arranged segments of constriction of the ileum were visualized by axillar slices and sagittal slices of MPR images as part of the routine study. The images showed a short closed loop sign in the left side of the pelvic space (Fig. ). The collapsed sigmoid colon was arranged in the ventral-dorsal direction and to the right side of the closed loop. Between the ascending and descending parts of the sigmoid colon, a right-to-left side arrangement of the intestinal mesentery was found, and the dilated intestine at the oral side of the herniated position was also observed at the right side of the sigmoid colon. The location of the incarcerated bowel suggested that the herniated orifice was located on the right side of the mesosigmoid, which was pushed to the upper-left side of the ventral-dorsally arranged sigmoid colon by the dilated intestine. The incarcerated short intestinal segment showed a good contrast effect by the enhanced study. Sagittal MPR images also showed narrow belt-shaped fluid retention on the tip of the incarcerated short loop toward the cranial direction alongside the psoas muscle, indicating that the fluid and the incarcerated small bowel were localized in the mesosigmoid (Fig. ). The patient was diagnosed with internal abdominal hernia, and IMSH was considered to be the most likely cause.
The patient first received non-operative treatment with peripheral infusion without oral intake. However, the obstruction did not resolve, and we decided to operate 2 days after admission.
A long tube was inserted, and the patient underwent laparotomy operation. Dilated intestine and serous ascites were observed; the ileum was approximately 75 cm proximal to the ileocecal junction and was found to be herniated into the mesosigmoid through the right leaf (Fig. ). The opposite side of the mesosigmoid was bulged by the incarcerated ileum and wrapped in the left leaf, without exposure of the ileum through the mesocolon. Attachment of the lateral aspect of the sigmoid mesocolon to the parietal peritoneum was normal. The incarcerated ileum was gently released by a pressing maneuver from the left leaf. The released ileum, 6 cm in length, appeared viable and without color change, and thus, resection of part of the ileum was not conducted (Fig. ). The orifice located at the central part of the right leaf was oval shaped and measured less than 2 cm in diameter (Fig. ). The left leaf of the mesosigmoid was intact. The orifice of the right leaf was closed by suture. After an uneventful recovery, the patient was discharged from the hospital 12 days after the operation.
We investigated the preoperative MDCT and reconstructed oblique coronal images using the SYNAPSE VINCENT® workstation (Fujifilm Medical Co., Ltd., Tokyo, Japan) after surgery. Oblique coronal images revealed the incarcerated intestine and the converging mesenteric vessels to indicate the hernia orifice more clearly, which measured 18 mm in width (Fig. ).
Internal hernia represented by paraduodenal hernia, pericecal hernia, and others is a rare cause of intestinal obstruction and is estimated as responsible for only 0.5–0.9% of intestinal obstruction in patients with no history of abdominal surgery [, ]. Among internal hernia cases, SMH, herniation involving the sigmoid mesocolon, is a rare subset and is estimated at approximately 6% of all internal hernia cases []. Benson and Killen classified SMHs into three types: intersigmoid hernia (ISH), transmesosigmoid hernia (TMSH), and IMSH []. ISH has been defined as herniation into the peritoneum fossa due to insufficient attachment of the left lobe of the mesosigmoid to the parietal peritoneum of the posterior abdominal wall, and TMSH and IMSH are herniation into abnormal (mostly congenital) oval-shaped defects of one side or both lobes of the mesocolon. IMSH is described as the rarest type of SMH (ISH 30/34, TMSH 3/34, IMSH 1/34, respectively) [].
Of the three types of SMH, TMSH showed the highest rate of bowel resection (50%) compared with ISH (18.8%) and IMSH (13.9%) []. SMH should be accurately diagnosed without delay, considering the risk of strangulation.
Regarding the modality to facilitate a precise diagnosis, MDCT is most useful; ISH cases should be visualized such that the small bowel goes across the ventral part of the sigmoid colon once, and then, the incarcerated small loop is formed from the lower-left abdomen to the cranial side because the hernia orifice of ISH is located at the attachment of the lateral aspect of the sigmoid mesocolon. In cases of TMSH and IMSH, as for the congenital oval-shaped foramen of the sigmoid mesocolon that can occur in both lobe sides, it is necessary to consider that the short bowel could herniate into or through the mesosigmoid from either side. However, it is difficult to preoperatively distinguish between IMSH and TMSH by MDCT.
In the presented case, routine sagittal MPR imaging showed narrow belt-shaped fluid retention contacting the tip of the herniated short loop of the intestine. This indicated that the fluid and the herniated small bowel were wrapped together in the mesosigmoid, which precisely indicated IMSH. This finding seems to be characteristic of IMSH and may be useful for conclusively differentiating this disease from TMSH.
Our case showed the characteristic findings noted above by routine sagittal MPR images and provided sufficient information on the IMSH before the operation; however, it is difficult to obtain high-quality image views of diagnostic value by routine images alone in many cases. Kumagai [] reported the usefulness of oblique multiplanar images on MDCT, and we investigated the preoperative MDCT and reconstructed oblique coronal images using the SYNAPSE VINCENT® workstation after surgery to visualize the hernia orifice and illustrate a more detailed anatomical placement. Oblique coronal images revealed the incarcerated intestine and the converging mesenteric vessels that more clearly indicate the hernia orifice in the mesosigmoid. Preoperative investigation of oblique multiplanar images on MDCT can help physicians understand the three-dimensional placement of the bowels of interest to facilitate accurate diagnosis of SMH.
Shibuya [] reported the usefulness of a laparoscopic operation for ISH. Regarding IMSH cases, application of the laparoscopic approach has not been rigorously reported. It seems that further study of the laparoscopic operation for IMSH is necessary, and the precise preoperative understanding of the anatomical placement of the bowel of interest would contribute to its safe application.
There are two points of reflection on the treatment course of this case. First, despite being able to diagnose IMSH from the images, surgery could not be performed immediately. Due to the rarity of this disease and the inexperience with image findings, we could not share our understanding of the disease condition among surgeons, and therefore, we were not able to comply with the emergency surgery policy. This report was motivated by our reflection and the need to publish on this disease and describe its characteristic imaging findings. A long tube was inserted before the operation using a routine technique at the time of an intestinal obstruction operation at our facility; however, it is thought that this will not be routinely necessary in the future because there are many reports in which a long tube was not used for IMSH operations, and the clinical course thereafter did not show any problems.
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pmc-6195911-1
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A 55-year-old non-diabetic, non-hypertensive male with a history of recurrent colicky left lumbar pain presented with acute urinary retention. Catheterization was attempted; however, it was unsuccessful. Ultrasound revealed an overdistended urinary bladder with a normal-sized prostate and scarring and focal caliectasis in the left kidney (). The right kidney was normal and no calculi were seen on either side on ultrasound. Serum electrolyte, renal and liver functions were normal. The haemogram revealed neutrophilia. The prostate-specific antigen was within normal limits. A rigid urethroscopy was performed owing to suspicion of a left urethral calculus and a 11-mm size calculus was removed from the posterior urethra. The patient was discharged and had no difficulty with micturition for 2 weeks thereafter. The patient subsequently developed burning micturition with hesitancy and induration in the perineal region. The urine was turbid and microscopy revealed the presence of Escherichia coli. A perineal ultrasound revealed an abscess in the perineum, which extended to the proximal parts of the corpus spongiosum (). This abscess was drained under saddle block. The patient subsequently developed a discharging sinus at the operative site () leaking purulent fluid. A retrograde urography revealed periurethral extravasation of the injected contrast material with a lytic lesion in the left pubic ramus (). A repeat perineal ultrasound revealed a linear hypoechoic tract leading from the skin surface to the corpus spongiosum (). A retrograde CT urography was performed to look for the extent and ramifications of the abscess. On the non-contrast CT scan, a lytic lesion was seen involving the left inferior pubic ramus (). The pubic symphysis and bodies of both pubic bones were normal. A proximal femoral nail was noted in situ on the left side, which was inserted 10 years before for fracture of the proximal shaft of the femur owing to accidental trauma. On injecting iodinated contrast into the urethra, there was extravasation of the contrast in the periurethral region in the soft tissues surrounding the bulbar and the posterior penile urethra. An extension of the contrast through the external anal sphincter into the intersphincteric plane () with inflammatory stranding in the ischioanal fossae was seen. The contrast also extended into the lytic lesion present in the left inferior pubic ramus (). The contrast also extravasated through the cutaneous opening in the perineum and the natal cleft (). E. coli were isolated on pus culture. The patient was treated with intravenous antibiotics and suprapubic cystostomy was performed. The patient is presently being considered for elective urethroplasty.
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pmc-6195912-1
|
A 49-year-old Caucasian female with no pertinent past medical or antecedent trauma history presented to neurosurgery with a 2-year history of progressive neck stiffness and spasm, left-sided jaw pain and left-sided headache. Her symptoms initially started with toothaches in the left jaw, for which a dental examination was normal. She subsequently developed worsening neck spasm and shooting pain extending from the superoposterior left neck into the left occiput, which was typically worse in the morning and aggravated by leaning to the left.
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pmc-6195915-1
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A 59-year old male presented to the chest clinic with a history of intermittent left-sided pleuritic chest pain and progressive breathlessness on minimal exertion. His past medical history included repeated episodes of chest infection and a persistent right mid-zone opacity on serial chest radiographs. At the time, all other investigations were negative, including testing for mycobacterial disease and a reportedly normal flexible bronchoscopy at an outside institution. He was treated for many years with intermittent oral antibiotics and chest physiotherapy. He was a former smoker (20 pack-years) and also had a history of Type II diabetes mellitus, chronic obstructive airways disease and myocardial infarction with percutaneous coronary intervention.
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pmc-6195920-1
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A 57-year-old female presented with a history of pain and swelling below the left knee, insidious in onset for 4 years with a sudden increase in size over the past 2 months. She also had swelling on the dorsum of the right hand. No significant limitations of movement were noted. No history of injury was given by the patient. An ultrasound of the knee joint showed multiple loculated cystic lesions involving the subcutaneous planes and the popliteal fossa with diffuse internal echoes (). It was suggested that she undergo an MRI of the knee for further evaluation, which showed multiloculated cystic lesions that were hypointense on T
1 weighted and hyperintense on T
2 weighted sequences around the knee joint with intra- and extra-articular components ( and ), and subcutaneous extension insinuating between the tendons, muscles and popliteal vessels (). A similar small lesion was seen at the non-weight-bearing surface of the lateral condyle of the femur, suggestive of an intraosseous lesion (). Hoffa’s fat pad was involved (). Underlying degenerative changes were noted in the bilateral knee joints. Similar cystic lesions were found around the right knee joint, right wrist, abductor pollicis longus, extensor pollicis brevis () and overlying the ring finger, in the flexor tendon at the proximal phalanx of ring finger (). Intraosseous involvement of the capitate and lunate were noted (). With all the above findings and in view of multiple joint involvement, the possibility of cystic ganglionosis or multiple giant ganglion cysts was considered. Aspiration of one of the knee lesions was performed, which yielded a gelatinous material. Fine-needle aspiration cytology showed cyst macrophages in clusters against proteinaceous–mucoid background, without any atypical cells. Also, biopsy of the lesion confirmed the diagnosis of a ganglion cyst (as described in ). As the lesion was diagnosed to be harmless, the patient was advised conservative management and follow-up. With multi-joint involvement of the ganglion cysts, the term “cystic ganglionosis” was used.
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