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pmc-6176309-1
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A 60-year-old healthy male patient (no comorbidities, never-smoker) with ARDS due to influenza A pneumonia was admitted to our specialised lung clinic for further treatment. Endotracheal intubation due to severe hypoxemic respiratory failure was already performed prior to admission (day 0). Transference of the patient to the hospital occurred on day 6. The first chest X-ray after admission revealed an apical left-sided pneumothorax of approximately 2 cm, accompanied by a large subcutaneous emphysema. Two chest tubes were inserted, one on each side. After that, the left lung was again fully expanded, the subcutaneous emphysema resolved, and no air leak could be observed. On day 14, the patient developed once again spontaneously a massive and progressive subcutaneous emphysema, accompanied by a large air leak of about 5000 ml per minute on the left side. A second and a third chest tube were inserted on the left, one in Monaldi's position (3rd intercostal space mid-clavicular) and the other in Bülau's position (5th intercostal space slightly anterior the mid-axillary line). However, the chest X-ray and chest CT-scan on day 16 showed a complete, left-sided pneumothorax (). Central venous catheter placement on the left (internal jugular vein) was performed six days before the onset of the air leak. We interpreted the occurrence of the air leak, the pneumothorax, and the subcutaneous emphysema as a result of barotrauma due to invasive mechanical ventilation. Because of progressive hypercapnia and severe respiratory acidosis, a tracheostomy was performed and a vvECMO (PLS Set and ROTAFLOW Console) was established (day 16), using an Avalon Elite™ Bi-Caval Dual Lumen Catheter (Maquet Cardiopulmonary GmbH, Germany). Blood gas analysis immediately before the start of the extracorporeal lung assistance revealed a PaCO2 of 88 mmHg with a pH of 7.30, and PaO2 was 90 mmHg. At this point, the patient was ventilated in the assist-controlled mode (BIPAP-ASB, Evita 4, Dräger®). FiO2 was 0.85, and Pinsp was set at 28 mBar with a PEEP of 7 mBar. This resulted in a tidal volume of approximately 400 ml and a minute ventilation of 8.4 l/min. After the cannulation of the patient and the commencement of vvECMO support, a lung protective ventilation strategy with low tidal volumes (Pinsp 20 mBar, PEEP 10 mBar, FiO2 0.6, VT 250 ml) was established. This resulted in acceptable blood gas values (PaCO2 49 mmHg, PaO2 74 mmHg, pH 7.52) on vvECMO (blood flow 2.5 l/min, FiO2-vvECMO 1.0, sweep gas flow 4.0 l/min); however, the air leak persisted (day 17), and in the chest X-rays the left lung remained collapsed. In the further course of treatment, the blood gas analyses revealed persistent hypercapnia with a PaCO2 of approximately 60–65 mmHg, and even though the sweep gas flow was increased, a state of normocapnia could not be achieved. Therefore, an interventional closure of the fistula with endobronchial valves was planned.
On the day of the procedure (day 21), FiO2 on the ventilator was 0.6, and Pinsp was set at 17 mBar and PEEP at 5 mBar, resulting in tidal volumes of about 450 ml and minute ventilation of approximately 9.2 l/min. vvECMO blood flow was 2.6 l/min with a sweep gas flow of 5.5 l/min. Valve placement was done bedside on the intensive care unit. The patient was under deep sedation/analgesia with midazolam and sufentanil, respectively. Cis-Atracurium (10 mg) for muscle relaxation was administered immediately before the procedure. Bronchoscopy was performed through the tracheal cannula. The exact bronchoscopic localisation of the fistula was assessed by occlusion of the upper and lower lobe bronchus on the left, using a bronchus blocker while measuring the fistula flow with the Thopaz Digital Chest Drainage System (Medela AG, Switzerland). First of all, as we blocked the left upper lobe bronchus (corresponding to the segment bronchi LB1–5), the air leak was stopped entirely. Then we occluded each segment of the left upper lobe separately, but we did not achieve any significant result. The occlusion of the lingula bronchus (LB4/5) had no significant effect on the air leak as well. Thus, decision was made to close LB1/2 and LB3 with two Zephyr® endobronchial valves (2 × 4.0-LP, Pulmonx®, Redwood City, USA). This initially led to an immediate decrease of the air leak to about 400–700 ml/min, and the left lung was then again fully expanded (). After valve placement, PaCO2 decreased slowly during the following six days, while there were no major adjustments of the ventilator settings or the vvECMO parameters. Normocapnia was detected for the first time on day 27, so that blood flow and sweep gas flow on vvECMO could be slowly reduced. During the following two weeks, the air leak stopped completely and the patient could be weaned from vvECMO on day 48. The patient was transferred from the intensive care unit to the weaning unit on day 61. Removal of the endobronchial valves occurred on day 62, after which the chest X-rays showed a persistently expanded left lung (). As there was no evidence of an air leak once again, the chest tubes were removed one after another, liberation from the ventilator on day 72 and discharge to neurological rehabilitation on day 89.
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pmc-6176312-1
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The patient was a 54-year-old male with multiple metastasis of axillary lymph nodes, lung, and intracranial and cervical vertebrae after liver cancer surgery. He had been experiencing severe, persistent needle-like pain in the right shoulder, back and right arm since 3 months. Other doctors treated the pain with fentanyl transdermal patch 29.4mg q72h and 100mg tramadol sustained release tablet q.d. oral prior to admission. However, neither analgesic therapy was effective in treating his pain. In addition, the patient had breakthrough pain (BTP) more than ten times in 24 hours, and NRS (Numerical Rating Scale) score was 7. Due to the poor analgesic effect of the tramadol sustained release tablets, they were discontinued, and the patient's condition was reassessed after admission. The patient felt pricking, numbness, and electrical shocks, suggesting an ID Pain scale [] (Neuropathic pain screening scale) score of 3. Since the ID Pain score accurately indicates the presence of a neuropathic component of pain, his pain was considered to be a combination of pathological neuralgia, and thus 600mg Gabapentin capsules were given t.i.d. orally starting on the day of admission.
NRS score was 4 at rest on day 2 of admission, BTP was 4 times at night, and NRS score was 7. One hour after administering 10mg morphine tablets, NRS score decreased to 3. Due to the weak effect of 29.4mg fentanyl, the concentration was increased to 42mg in the transdermal patch. At the same time, 5mg dexamethasone injection IV q.d., oral 25mg amitriptyline tablets 25mg q.n., and oral 2mg Clonidazepam tablets q.n. were given.
On day 7 of admission, the patient still complained of obvious pain in the back, shoulder, and right arm, NRS score was 5 at rest, BTP was 3 times at night and NRS score was 8. In our patient, imaging showed multiple soft tissue masses in the neck space, corresponding to metastases. Since the spinal canal becomes narrow and results in cerebrospinal fluid reflux in such a condition, the tip of the catheter was inserted in the cerebellomedullary cistern. Intrathecal pump was implanted in the cisterna magna under DSA without any complications in the First Affiliated Hospital, Zhejiang University School of Medicine (). Morphine is one of the FDA recommended drugs for full implantable infusion pumps, and a conservative starting dose is recommended for intrathecal administration. The patient was given 50mg morphine dissolved in 200ml saline via the intrathecal pump. Since the patient was treated with 42mg fentanyl transdermal patch before surgery, the initial parameters of drug infusion were continuous background dose (Con) of 0ml and single enhancement dose (bolus) of 0.8ml for 0.2mg morphine. Some studies recommend that the maximum dose of morphine in cerebellomedullary cistern should not exceed 0.5mg [], with locking time 20min and electrocardiogram (ECG) and O2 saturation monitoring. The intrathecal pump parameters could be adjusted according to the degree of pain and drug reaction experienced by the patient. In the period between operation and 8:00am on day 8 after operation, the patient pressed bolus 15 times and the effective number was 8 times. Since the pain was not relieved even after pressing, the parameters were adjusted to Con of 0.3ml/h and bolus of 1ml with 0.25mg morphine. Meanwhile, fentanyl dose in the transdermal patch was reduced to 33.6mg. After adjusting the pump's parameters, the NRS score was 1 at rest, the time of BTP was 4, and the NRS score was 4. According to the equivalent dose of opioid drugs and related efficacy conversion, the intrathecal dose of morphine is about 300 times more than its intravenous form. When the pain stabilized, fentanyl dose in the transdermal patch was further reduced to 25.2mg after expiration, and the amount of morphine infused via the intrathecal pump was reduced daily. The degree of pain was significantly reduced compared with that before surgery. Taken together, administration of analgesic via intrathecal pump implantation in the cisterna magna reduced pain levels and reduced the number of BTPs. The patient experienced considerable pain relief (see ). However, the patient had terminal cancer and died of multiple organ failure on day 13 after admission.
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pmc-6176314-1
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A 15-year-old girl presented with a background of erratic menstrual periods following menarche at age of 12 years. By first contact she had experienced amenorrhoea for 6 months followed by continuous daily vaginal bleeding for 3 months. She had noticed hair loss, receding hairline, and coarse dark hair on her abdomen, thighs, and bottom. Clinical examination revealed a normally developed female without virilisation of the external genitalia or a change in voice. She was pain free.
Hormone profile revealed raised testosterone (10.1nmol/l Ref: 0.5-3.0 nmol/l), suppressed FSH (<0.1 IU/L Ref: 1-11 iu/L), and borderline SHBG (21 nmol/l Ref: 18 – 114 nmol/L). AFP was raised (137 kU/L Ref: 0-5.8 kU/L) but all other tumour markers, including Beta-HCG and Inhibin, were normal. Urine steroid profile was normal.
Ultrasound examination of the abdomen and pelvis, , revealed a complex 7 cm left ovarian lesion with internal vascularity but otherwise normal pelvic organs and adrenal glands. MRI, , confirmed an abnormal but well-defined 7 cm left adnexal lesion of predominant intermediate T2 signal interspersed with high signal cystic areas separated by low signal septa. The clinical picture was of a primary ovarian tumour with ectopic production of androgens, and not the more common germ cell tumour.
The case was discussed at the paediatric and gynaecologic oncology MDT. A laparoscopic left oophorectomy with preservation of the ipsilateral fallopian tube was performed with a secondary Pfannenstiel incision used to extract intact the specimen. The tumour which was more solid than cystic was 11 cm in size with no discernible normal ovarian tissue visible. A small nodule on the right ovary was excised. There were no other sites of disease. All other organs and peritoneal surfaces were normal. The postoperative course was uneventful.
Histological analysis, Figures and , indicated a predominantly poorly differentiated Sertoli-Leydig cell tumour, retiform pattern, with heterologous mucinous elements. The right ovarian nodule was benign.
Following multidisciplinary team discussion and parental consent, adjuvant chemotherapy was commenced, in a monthly regime of Bleomycin 28500 IU on Day 1, Etoposide 190 mg daily on Days 1-5, and Cisplatin 38 mg daily on Days 1-5 for 3 cycles. Starting prior to chemotherapy commencement, a GNRH analogue, Leuprorelin 3.75mg per month, was administered for 4 months for ovarian protection. The patient became neutropenic following cycle 1 and received Filgrastim 300mcg for 6 days on Days 6-10 of Cycle 2. There were no further episodes of neutropenia. Following cessation of Leuprorelin, menstruation resumed on a regular monthly cycle. She completed her treatment 2 years ago and been reviewed every 3 months. She has had normal tumour markers, including testosterone and AFP, and normal abdominopelvic ultrasound scans throughout this period. Following genetic analysis a germline DICER1 mutation was discovered, inherited from her father and shared by her 19-year-old sister.
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pmc-6176323-1
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We present the case of a 30-year-old Nigerian male who was brought to the Surgical Emergency Department of the Lagos State University Teaching Hospital Ikeja 22 hours after he had inserted a constricting ring over his penis. He had developed a painful penile shaft swelling distal to the ring with suprapubic pain and swelling secondary to acute urinary retention. There was associated urethral bleeding.
There had been failed attempts at removing the ring by self and the resulting severe pain drew the attention of his relatives who brought him to the emergency room.
He had a history of a psychiatric illness and the patient claimed he was under a spell and had heard a voice that instructed him to insert a ring over his penis. He denied using the ring to sustain erection and claimed it was his first time of inserting a ring over his penis.
The patient had a history of deterioration in personal and general performance with underachievement dating back to 7 years prior to presentation when he voluntarily dropped out of the university and had done nothing tangible thereafter.
Two weeks prior to presentation, the patient's relatives had noticed some unusual behavior in him characterized by talking to self and rubbing salt over his body and the patient claimed he was being chased by unseen people.
He had a history of alcohol, cigarette, and cannabis abuse for about 15 years.
On examination, he was in acute urinary retention with a tender suprapubic distention up to the level of the umbilicus.
There was a thick constricting ring at the root of his penis. There was a markedly swollen oedematous penis distal to the ring with marked reduction in sensation over the penis and glans ().
We made a diagnosis of Constrictive Penile Injury (Bhat Grade III) with acute urinary retention [].
He had a suprapubic cystostomy done to relieve the acute urinary retention as a urethral catheterization was impossible.
Attempts were made to remove the constricting ring by the use of aspiration, application of cold compress, and lubrication initially and later by the use of the string method.
Following failed attempts at removing the device with these different manipulations and unsuccessful attempt at cutting with the manual saws available in the hospital coupled with the fact that the patient appeared to have imminent penile gangrene, a decision was made to call the fire service for a power driven saw.
The ring was successfully removed by cutting it at two different points () with a power driven arc saw () under conscious sedation at the emergency room.
Thermal injury was prevented by intermittent cooling with ice packs and injury to underlying tissue was prevented by insinuating a pair of artery forceps between the penis and the ring ().
Dressing of the resulting penile skin ulceration was done and the plastic surgery team was invited for possible additional wound care.
The patient was also reviewed by the psychiatric team who made a diagnosis of schizophrenia and commenced the patient on haloperidol. He was to be followed up on an outpatient basis in the psychiatry clinic.
The patient reported normal nocturnal erections while on admission. Further evaluation of the suspected urethral injury with urethrogram and a urethroscopy was planned but this was declined by the patient who opted to retain his suprapubic catheter.
The patient also declined any additional wound care by the plastic surgery team and the wound was healing satisfactorily by secondary intention as at 2 weeks after the initial presentation ().
He subsequently defaulted from care.
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pmc-6176343-1
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A 24-year-old woman was admitted to the Department of Infectious Disease with fever (T = 38,3°C) which was attributed to a relapse of a IM-HLH occurring about two months prior to the current hospitalization. At that time, the diagnosis of IM was confirmed by the presence of EBV DNA in the bloodstream and the diagnosis of HLH was suspected on the basis of the clinical findings such as persisting fever, the enlargement of the liver and the spleen as well as of blood abnormalities including pancytopenia, abnormally elevated values of ferritin (> 15.000 mcg/ml), triglycerides (789 mg/dl), and liver enzymes (AST 175 U/L, AST 120 U/L); a bone marrow biopsy confirmed the presence of hemophagocytosis and viral RNA in many cells by means of in situ hybridization (EBER) []; a genetic screening excluded the presence of gene mutations associated with HLH. During that hospitalization, she received steroids, etoposide, rituximab, cyclosporine, granulocyte-stimulating factor, and intravenous immunoglobulins (IvIg) and was ultimately discharged 38 days after the initial admission without viral DNA detectable in the bloodstream. During her stay at home, which lasted 3 weeks, the patient received prednisone, cyclosporine, trimethoprim-sulphametoxazole and acyclovir through a peripherally inserted central venous catheter (PICC). Thirty-six hours after the current admission during which rituximab was added to the ongoing treatment she was transferred to the ICU due to the deterioration of the consciousness, arterial hypotension, and fever. At the ICU admission, the patient presented high fever (40,5°C), disseminated intravascular coagulation, arterial hypotension, and acute kidney injury requiring renal replacement therapy (RRT): a methicillin-resistant Staph. aureus (MRSA) was isolated from the blood cultures and a septic shock-related MODS possibly in association with a cytokine storm caused by the HLH were hypothesized; the patient was intubated and mechanically ventilated and treated with IV vasopressors at incremental doses, IV vancomycin, meropenem, and caspofungin; the PICC was removed and replaced with a central venous catheter; as the patient remained unresponsive to the treatment, a Coupled Plasma Filtration and Adsorption treatment (CPFA, LYNDA®, Bellco, Mirandola, Italy) that aimed at removing the inflammatory mediators was added to the RTT along with the IV administration of IgM and IgA-enriched IvIg (Pentaglobin®, Biotest; Dreieich, Germany). Despite this increasingly aggressive approach, the MODS further worsened and the patient died 18 hours after the ICU admission.
At the autopsy, the liver and the spleen appeared enlarged, weighting 3110 g and 1230 g, respectively. Microscopically, the spleen showed lymphocyte depletion and the scattered necrosis of Malpighi's follicles () combined with subversion of the general architecture due to a proliferation of T-lymphocytes (CD3+) with predominant expression of CD8 (). The lymphocyte population B (CD20+, PAX-5+) was virtually absent, while there was a significant increase in monocyte-macrophage component sometimes associated with hemophagocytosis. The EBER highlighted several lymphocytes with integrated EBV RNA in the nucleus (). The liver showed several perivascular infiltrates of polymorphic lymphocytes likewise those found in the spleen and many monocyte-macrophage cells (CD14+, CD64+). In the bone marrow there were multiple lymphocyte with polymorphic or abnormal nucleuses () that appeared to be almost exclusively CD8+ T-lymphocytes (). Most of these cells were EBER positive (); B-lymphocytes (CD20+, PAX-5+) were almost absent while there was an expansion of the monocyte-macrophage series (CD14 +, CD64 +). The three hematopoietic lines appeared contracted but with preserved maturation. Mediastinal lymph nodes showed a diffuse proliferation of medium/large sized lymphoid elements, sometimes with single or multiple polymorphic nuclei (). The lymphocyte population was composed by CD3+ CD8+ T-lymphocytes with a limited presence of lymphocytes CD3+ CD4+ and absence of B cells (CD20 +, PAX-5 +).
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pmc-6176504-1
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A 66-year-old male presented with the left cervical and submaxillary lymph node enlargement with size of 30 mm × 30 mm. The following lymph node biopsy was completed and the pathological evaluation showed reactive lymphoid hyperplasia characterized by vascular, atrophic germinal lesions with surrounding concentric “onion skin” layers of lymphocytes (Fig. ), defined as the hyaline vascular variant of CD. He denied weight loss, lymphadenopathy, tuberculosis, diabetes mellitus and hypertension. He gave no history of bone pain and drug abuse. The bone marrow (BM) cytology indicated no clonal plasma cell infiltration. Thereafter the patient was treated with irradiation dose of 30 Gy in 10 fractions with clinical response. The clinical evaluation remained stable in annual follow-up visits. In the 4th visit, the patient was diagnosed in an outside hospital with 2-diabetic mellitus on basis of increased blood glucose, C peptide release test and oral glucose tolerance test (OGTT). The blood glucose was well-controlled by the hypoglycemic and diet therapy for three years when he presented to the previous hospital with progressive hand-foot numbness spreading from the proximal extremes to distal ends. The electromyography test confirmed the hampered nerve conduction velocity of bilateral ulnar, median and peroneal nerves. The cerebrospinal fluid (CSF) biochemistry from lumbar puncture indicated the slightly elevated protein (1.1 g/L, normal, 0.1~ 0.4 g/L) with normal cell count. The blood monoclonal protein level and bone marrow cytology was normal. Based on the resultant diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP), the patient was treated with daily intravenous pulse methylprednisolone therapy of 1.0 g for three consecutive days. Due to the minor clinical response, the diabetic peripheral neuropathy was suspected with following insulin injection and oral mecobalamin therapy. However, the manifestation of hand-foot numbness remained constant. One and half years after the first sign of numbness, the muscular dystrophy of palms was noticed with finger fine hypoactivity. In the next 2 years, the patient was admitted to the previous hospital with the progressive muscular atrophy, numbness of hands and myasthenia of limbs along with interphalangeal deformity. The CSF test showed slightly elevated protein concentration (1.6 g/L) with normal pressure, cell count and the level of glucose and chloride. Other laboratory results were normal. The electromyography test was performed with severe neuro-electrophysiological damage in bilateral median, ulnar, peroneal and tibial nerves. Despite the intensive glucose control and oral mecobalamin therapy for the next seven years, the symptom of limb numbness and trembling was significantly worsened. In parallel, the skin pigmentation with increasing body hair and skin elasticity loss was also noted. He gave the history of insomnia for seven years but denied smoking and alcohol abuse history. Insulin and oral anti-diabetic drugs was thereafter withdrawn at the normal level of HbAlc and blood glucose.
The physical examination revealed that skin was thickened with hyperpigmentation over the toes (Fig. ). Other abnormal neurological examinations include the limb hypoesthesia, static tremor of hands, tendon hyporeflexia and positive Romberg sign. The thorax and abdominal CT scanning showed interstitial pneumonia and nodules located in right lobe, a small amount of pericardial effusion, hemorrhagic cyst on the pole of right kidney and splenomegaly (Fig. ). The pituitary gland MRI showed the shrunk size of pituitary gland concurrent with partial empty-sella and nasosinusitis. The ultrasonography excluded lesions of adrenal glands but discovered bilateral thoracic effusion post CT scanning. The electromyography test was repeated with severe to complete neuro-electrophysiological damage in bilateral median, ulnar, peroneal and tibial nerves and movement loss of tibialis anterior muscle and abductor muscle of right little finger. Laboratory investigations revealed a platelet count of 454 × 1012/L (normal, 125~ 350 × 109/L), triglycerides level of 1.8 mmol/L (normal, 0.5~ 1.7 g/L), albumin of 20 g/L (normal, 35~ 50 g/L), adrenocorticotropic hormone (ACTH) level of 322.0 pg/ml which fell to 227.0 pg/ml (normal, 0~ 46 pg/ml) after one week. Her CRP level was 17.7 mg/L but rose to 21.3 mg/L (normal, 0~ 3.0 mg/L) within 2 weeks. The blood cortisol level in the morning was 220.3 nmol/l (normal, 138~ 690 nmol/L) within one week. The coagulation function showed PT-SEC of 15.6 s (normal, 10.0~ 14.0 s), PT% of 49.4% (normal, 70.0%~ 130.0%) and APTT-SEC of 44.2 s (normal, 20.0~ 40.0 s). The serum immunoglobin test indicated moderately increased IgG level of 11.9 g/L (normal, 7.6~ 11.6 g/L) and decreased complement C3 level of 0.5 g/L (normal, 0.8~ 1.4 g/L). Viral serology (EBV and HSV not included), urine free cortisol, tuberculosis antibody, sex hormone test, thyroid hormone and tumor biomarkers were undertaken and came back with normal value. BM cytology revealed significant hypercellularity and thrombocythemia. Genetic tests from BM biopsy showed negative expression of JAK-2 gene and BCR/ABL gene fusion, therefore the primary thrombocytosis was diagnosed instead of multiple myeloma. Abnormal hyperimmunoglobulinia appeared as minimal IgG-lambda monoclonal protein variant (Fig. ). The clinical presentation and investigations consisted with features of POEMS syndrome. The patient was managed with daily oral prednisone of 20 mg and azathioprine of 150 mg for 2 weeks. The numbness was apparently relieved with improved performance status. Thus, thalidomide with oral dose of 50 mg daily was taken as maintenance therapy. Clinical monitor of response and toxicity was evaluated periodically within the next 2 years and the patient rejected medical treatment and died of hypoalbuminemia, electrolyte disturbance and pneumonia.
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pmc-6176516-1
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A 17-year-old Caucasian boy was admitted to our intensive care unit (ICU) after successful resuscitation by emergency services. While performing running exercise in a fitness center, he suddenly collapsed. Because neither pulse nor breathing could be detected by the bystanders, immediate resuscitation was performed. In the first heart rhythm analysis conducted by the paramedics, ventricular fibrillation (VF) was seen and immediately defibrillated into sinus rhythm. The patient recovered quickly and was transferred to our ICU by the ambulance service. At admission, the patient was in hemodynamically stable condition with normal vital signs (heart rate 95/min, blood pressure 125/79 mmHg, auricular temperature 36.5 °C, respiration 15 breaths/min, oxygen saturation of 100% on 4-L nasal cannula). The physical examination revealed no abnormal findings. Auscultation of the heart showed a regular rate and rhythm with normal S1 and S2 and no murmurs or rubs. The breath sounds of the lungs were equal and clear bilaterally with no wheezes, rhonchi, or rales. The patient was awake (Glasgow Coma Scale score of 15) and orientated in all aspects. No focal sensory or motor deficits, aphasia, or inadequate balances were noted in the neurological examination. Deep tendon reflexes and cranial nerves II through XII were intact. Because there were no cerebral or other sequelae at the time of hospital admission, we decided not to obtain a cranial computed tomographic scan, owing to the patient’s young age. When asked about the event, he told us that he had no symptoms prior to the collapse. However, in the years before, he had syncopated several times while climbing stairs, playing soccer, and once when he got frightened. A general practitioner previously performed an exercise ECG, which showed multiple premature beats under submaximal stress (Fig. ). As a result, beta-blockers were prescribed (metoprolol succinate 47.5 mg once per day). Apart from this, the patient had no medical history or prior medication. The patient was a nonsmoker with no regular alcohol consumption and an unremarkable family, social, and environmental history.
At ICU admission, initial medical treatment included the first surface ECG after cardiac arrest, which showed negative T-waves in V1 and biphasic T-waves in V2 (Fig. ). The results of blood tests showed normal findings without signs of cardiac ischemia or metabolic disorders (Table ). Respiratory disorders (bronchospasm, aspiration) or neurovascular events seemed to be unlikely because the physical examination, blood gas analysis, and a pulmonary x-ray showed normal findings. An echocardiogram revealed normal left ventricular function without wall motion abnormalities, right heart strain, or valve disease. Additionally, a cardiac magnetic resonance imaging scan was performed and showed normal findings. Therefore, we ruled out hypertrophic and dilative cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and acute myocarditis as potential differential diagnoses. Further diagnostic workup included coronary angiography and electrophysiological testing, but none of those resulted in any relevant finding.
Because no extracardiac cause or structural heart disease was found, diagnostic workup focused on channelopathies and genetic heart diseases. Owing to the patient’s medical history of stress-dependent syncope, we strongly suspected a CPVT as the underlying mechanism for VF. Genetic screening was performed and confirmed the diagnosis of CPVT, revealing a new heterozygous point mutation in the gene for ryanodine receptor type 2, which, to the best of our knowledge, has not been described to date in the literature. The heterozygous mutation c.12520T>A (p.F4174 l, exon 90, RyR2 gene) results in an exchange of phenylalanine to isoleucine at position 4174 of the RyR2 protein. Forty-five percent of the relevant mutations of RyR are located in this region []. This novel identified missense mutation is located in the C-terminal channel region as a residue of the hydrophobic side chain of the S6/U motif interface of RyR2 [].
Prediction algorithms for forecasting functional effects of a mutation clearly identify this mutation to potentially cause CPVT []. Genetic screening of both parents showed that neither of them were carriers of the mutation. Results of further screening of the patient and family members for other pathogenic mutations (long or short QT syndrome, Brugada syndrome) were also negative.
On the basis of of our findings, the patient received an ICD device to protect him from recurrent episodes of VF. Additionally, oral medication with a beta-blocker was continued with the maximum tolerable dose. Because of the relatively small number of documented arrhythmic episodes, we did not add flecainide at that point. Left ventricular sympathetic denervation was discussed with the patient and the family, but in the end it was deferred.
At hospital discharge, the patient was included in our home monitoring program for ICD surveillance. Shortly after implantation, the ICD terminated a sustaining VT by antitachycardic pacing (Fig. ). This episode occurred early in the morning while the patient was asleep, which is an uncommon situation for arrhythmic events in patients with CPVT. However, the patient had no memory of a possible emotional stress due to dreams. In the following 6 months, a single episode of VF occurred during a physical activity (cycling), this time terminating spontaneously.
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pmc-6176649-1
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A 19-year-old male presented to the emergency department with a two-week history of pleuritic chest pain, dyspnoea, and non-productive cough. He denied fevers, night sweats, or weight loss. He had no articular, cutaneous, or ocular symptoms. He had mild childhood asthma in the past. He was not on any regular medications. There was no significant family history. He had moved to New Zealand from Fiji eight years earlier. He had regularly smoked tobacco through a “shisha” pipe for the preceding 3 months.
On examination, he was afebrile, with a heart rate of 90 beats per minute, blood pressure of 110/80 mmHg, and oxygen saturations of 98% on air. His cardiac and respiratory examination was normal. His abdomen was non-tender without evidence of masses. He had no peripheral lymphadenopathy. His testicular examination was normal.
A full blood count showed normal haemoglobin of 147 g/L (normal range 130–175), white blood cell count of 8.8 × 109 (normal range 4–11), and eosinophil count of 0.2 × 109 (normal range 0–0.5). C-reactive protein was 25 mg/L (normal range 0–5).
His chest radiograph showed multiple ill-defined opacities in both lower lung fields. A subsequent computed tomography (CT) scan of the chest and abdomen (Fig. ) showed multiple poorly marginated and irregularly contoured enhancing nodules through both upper and lower lobes bilaterally, more numerous at the bases. There were no pleural effusions or lymphadenopathy, and appearances of the abdomen were normal.
Further blood tests showed a negative antinuclear antibody (ANA), extractable nuclear antigen (ENA) panel, anti-neutrophil cytoplasmic antibodies (ANCA), serum angiotensin-converting enzyme (ACE), alpha-feto protein, Beta human chorionic gonadotropin (hCG), and Quantiferon-Gold.
He proceeded to a CT-guided fine needle aspirate and core biopsy of the most peripheral lesion in the left lower lobe. Histology (Fig. ) demonstrated preserved lung alveoli but prominent expansion of the lung interstitium with frequent necrotizing granulomas. There was a mixed inflammatory infiltrate of lymphocytes and occasional plasma cells and eosinophils. Fungal and mycobacterial stains were negative, as was culture for bacteria, mycobacteria, and fungi. Mycobacterium tuberculosis polymerase chain reaction (TB PCR) on biopsy specimen was negative. There was no evidence of malignancy, vasculitis, or foreign bodies, nor any features of Langerhans cell histiocytosis (LCH). Cell marker studies showed no evidence of monoclonality. Overall, the pathology impression was of necrotizing granulomatous inflammation.
The patient was given no specific treatment other than simple analgesia. While awaiting the histology results, he was discharged home with advice to avoid further shisha tobacco. Serial chest radiographs were performed at intervals of two weeks, six weeks, 12 weeks, and nine months. These demonstrated progressive resolution of the pulmonary opacities, with a clear chest radiograph at 12 weeks (Fig. ). A spirometry performed at nine months was normal.
The impression was of bilateral pulmonary granulomatous nodules most likely related to shisha smoking, with complete resolution following cessation.
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pmc-6176746-1
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Our patient is a 27-year old female that denied any past medical and surgical history. Her family and drug history were also unremarkable. The patient presented with a 7-month history of progressively enlarging mass on her left ring finger. The patient mentioned that the mass appeared suddenly with no history of trauma and that she was concerned about the potential malignant nature of the mass. The patient also mentioned that she underwent incision and drainage of that mass 2 months after its appearance with no improvement and provided no detailed surgical or pathological reports, which was the reason for her delayed presentation. Upon her assessment, the mass was located over the ulnar side of the proximal phalanx of left ring finger with extensive involvement of the 4th web space. The overlying skin coverage was ulcerative with no active signs of infection. Range of motion of the involved digit was limited, however neurovascular examination was normal. ().
Radiological evaluation of the involved hand showed a soft tissue swelling with no evidence of bone involvement (). Further magnetic resonant (MRI) evaluation showed a mass on the volar aspect of the ring finger encasing about 50% of the flexor tendons of that digit with low signal intensity on T1 and high signal intensity on T2 evaluation with strong enhancement in post contrast evaluation. Assessment of neurovascular structures showed partial abutment of the radial sided bundle together with complete encirclement of the ulnar sided neurovascular bundle. The surrounding bone was free of any masses and associated mass effect.
The patient was taken to the OR for exploration and mass excision by the senior author. Possible risks associated with such intervention were explained. Intra-operatively, bruner type incision was designed together with island of skin involved in the mass. Exploration revealed extensive subcutaneous mass with fibro-fatty consistency with extensive fascia like extension to the surrounding soft tissue. The mass was encircling the ulnar neurovascular bundle with mass abutment over the radial bundle as seen in pre-op assessment. The mass was dissected freely from its attachment to those bundles preserving both radial and ulnar structures. The mass was then excised en-bloc having a dimension of 3.5 × 4x2.5 cm (). Histological assessment showed a lesion with fasciitis like features, myofibroblastic proliferation and scattered foci of osteoid formation that was positive for Alpha-Smooth Muscle Actin (ASMA 1A4) immune staining and no evidence of malignancy (). The resected margins were however, positive for residual lesion with difficulty in obtaining negative margins due to the extensive nature of the mass. Post-operatively, the patient had an un-eventual course. She was informed about the need for close follow-ups for both clinical and/or radiological signs of lesion recurrence, pending early surgical intervention (see ).
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pmc-6176846-1
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A 76-year-old man visited a local clinic with icteric conjunctivae. He had sick sinus syndrome and used a pacemaker. Blood biochemistry revealed significantly high levels of total bilirubin and transaminase, and US imaging demonstrated intrahepatic bile duct dilatation. Therefore, he was referred to our department for examination of suspected obstructive jaundice.
On admission, the patient’s body temperature was 35.9 °C, and yellowing of the conjunctivae and skin was evident. The patient had medium build, and no abnormal findings were evident in the neck or thoraco-abdominal region. Blood tests on admission showed no abnormality, but blood biochemistry revealed significant increases in the levels of transaminases and biliary enzymes (glutamate oxaloacetate transaminase (GOT): 260 U/L, glutamate pyruvate transaminase (GPT): 420 U/L, γ-glutamyl transpeptidase (γ-GTP): 1166 mU/mL, and alkaline phosphatase (ALP): 1163 U/L). The total bilirubin level was 6.0 mg/dL. Examination of tumour markers revealed a carcinoembryonic antigen (CEA) level of 3.0 ng/mL and a high level of cancer antigen 19-9 (CA19-9) (194.1 U/mL) ().
Endoscopic retrograde cholangiopancreatography (ERCP) revealed disruption of contrast medium flow from the confluence of the cystic and common hepatic ducts through the distal bile duct, as well as significant dilatation of the common and intrahepatic bile ducts. Therefore, an endoscopic retrograde biliary drainage (ERBD) stent was inserted for biliary drainage (a). Brush cytology at the site of distal bile duct stricture demonstrated class V (adenocarcinoma).
Abdominal computed tomography (CT) scan revealed a contrast-enhanced lesion that filled the lumen of the bile duct from inside the distal bile duct. This lesion did not extend beyond the walls of the bile duct, and neither infiltration into other organs nor no clear lymphadenopathy was observed (b). Positron emission tomography (PET)-CT scan revealed accumulation of fluorodeoxyglucose (FDG) that coincided with the lesion in the bile duct, and there were no clear findings of distant metastasis (c). Based on these results, we made a preoperative diagnosis of distal bile duct carcinoma (T1N0M0) according to the Union for International Cancer Control (UICC) classification and performed pancreatoduodenectomy with regional lymphadenectomy.
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pmc-6176965-1
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A 62-year-old man with diabetes presented with general malaise, shortness of breath, and bradycardia. His medical history included retroperitoneal fibrosis, enlargement of the pancreas, and symmetrical swelling of the lacrimal glands with elevated serum IgG4 levels (175 mg/dL). He had received steroid therapy for 1 year for suspected IgG4-RD.
A physical examination revealed a blood pressure of 90/42 mmHg, a pulse rate of 42 b.p.m., and body temperature of 36.6°C. An early diastolic murmur was noted on auscultation. The laboratory test results revealed elevated levels of white blood cells (WBC, 17 800/mm3), C-reactive protein (CRP, 4.07 mg/dL), and erythrocyte sedimentation rate (ESR, >120 mm) in the first hour. The serum IgG4 level was within the normal range (101 mg/dL) under oral prednisolone treatment (10 mg/day). An electrocardiogram revealed a complete atrioventricular block. A chest radiograph showed a normal cardiac silhouette and clear lung fields. Although echocardiography revealed a normal aortic valve 1 year ago, a transthoracic and transoesophageal echocardiography now revealed a thickened tricuspid aortic valve and the LVOT wall with severe aortic regurgitation, but no evidence of aortic stenosis and LVOT obstruction (Figure ). The left ventricular (LV) systolic function was preserved, without wall motion abnormalities, and the LV end-diastolic diameter was slightly increased (Table ). A contrast-enhanced computed tomography (CT) of the chest showed a thickened aortic valve extending to the LVOT wall and normal thickness of the ascending aortic wall (Figure ). A cardiovascular magnetic resonance (CMR) revealed a high-intensity signal around the aortic valve in the late gadolinium enhancement, whereas there was no significant change in the myocardium, the ascending aortic wall, and the surrounding structures.
We increased the oral prednisolone to 30 mg/day after three days (1 g/day) of high-dose methylprednisolone for clinically suspected IgG4-RD of the aortic valve. The complete atrioventricular block improved to a first-degree atrioventricular block within a few days. Thus, he avoided permanent pacemaker implantation. He received an angiotensin receptor blocker (olmesartan 10 mg/day) and a long-acting loop diuretic (azosemide 60 mg/day) as a medical therapy for aortic regurgitation-related heart failure. The inflammatory markers CRP and ESR gradually returned to within the normal range, and his serum IgG4 level decreased further (56.3 mg/dL). A follow-up echocardiography demonstrated a slight regression of the thickened aortic valve and the LVOT wall. We thus decreased the oral prednisolone to 25 mg/day after 1 month of administration and initiated azathioprine (50 mg/day). A follow-up contrast-enhanced CT showed regression of the thickened aortic valve and the LVOT wall (Figure ).
Nevertheless, he presented with worsening shortness of breath and malaise three months after increasing the corticosteroid dose. Plasma brain natriuretic peptide increased from 69 pg/mL to 414 pg/mL, whereas the serum IgG4 level decreased to 27.6 mg/dL. The chest radiograph showed pulmonary congestion and cardiomegaly. The transthoracic echocardiography revealed the progression of aortic regurgitation and an enlarged LV dimension, whereas the aortic valve and LVOT wall thickening regressed. The LV systolic function was preserved, with no evidence of significant aortic stenosis and no LV wall motion abnormalities (Table ).
He underwent aortic valve replacement for severe symptomatic aortic regurgitation and heart failure deterioration. The patient received a bioprosthetic aortic valve (25-mm Carpentier-Edwards PERIMOUNT; Edwards Lifesciences, Irvine, CA, USA), as we were concerned about the risk of anticoagulation-related bleeding and the possibility that there could be problems further down the line with complications from multiple organs and ongoing anticoagulation. During the operation, we observed the thickening and shortening of the tricuspid aortic valve (Figure ). The entire LVOT wall was also thickened. In contrast, the ascending aorta was normal. The pathological examination of the excised valve leaflets showed a dense lymphoplasmacytic infiltrate mixed with fibrotic tissue. The immunohistochemical staining revealed a ratio of IgG4-positive plasma cells to IgG-positive plasma cells greater than 0.5 (Figure ). Thus, he was diagnosed with IgG4-RD of the aortic valve.
The dose of prednisolone was tapered by 2.5 mg every 2 months in combination with azathioprine 50 mg after surgery. The transthoracic echocardiography 1 year after the surgery showed regression of the LV dilatation and normal function of the prosthetic valve.
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pmc-6177024-1
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An 83-year-old male patient was emergently admitted to the hospital with the chief complaint of progressive dyspnoea over several days due to acutely decompensated HF (NYHA-IV) with hypotension (60/42 mmHg), bradycardia, and an irregular pulse (30 b.p.m.). The patient was uneventful for recent several years, and was not on any regular medication, including cardiovascular drugs, before the present admission. Table shows the clinical course of his HF-related tests, peripheral blood and urinary tests, and medications given to treat the decongestion and electrolyte disturbance. Physical examination on admission revealed jugular venous distension, systemic oedema, bilateral basal pulmonary rales, distant heart sound, and peripheral coldness. A 12-lead electrocardiogram revealed sinus arrest with a junctional escape rhythm and an irregular heart rate of 30 b.p.m. A chest X-ray revealed mild cardiomegaly (cardiothoracic ratio 55%) and prominent vasculature in the upper lung fields. Transthoracic cardiac ultrasound revealed a moderate degree of aortic regurgitation (III/IV), but the left ventricular ejection fraction (60%) was preserved, and its diastolic volume was almost within the normal range (143 cc). Thoracic and abdominal ultrasound showed massive bilateral pleural effusion and an expanded inferior vena cava with minimal respiratory change.
Urgent initiation of a noradrenaline drip infusion (2–3 μg/kg/h) and beta stimulant adhesive skin patch (Tulobuterol 2 mg/day) promptly restored the sinus rhythm (70 b.p.m.) and the normality of conduction and the QRS complex on electrocardiography, resulting in the recovery from hypotension with a systemic blood pressure of 117/56 mmHg. Blood tests on admission revealed moderately elevated b-type natriuretic peptide (BNP 576 pg/mL; normal range <18.4 pg/mL), hyponatraemia (128 mEq/L; normal range 135–147 mEq/L), hypochloraemia (95 mEq/L; normal range 98–108 mEq/L), hyperkalaemia (5.7 mEq/L, normal range 3.6–5.0 mEq/L), and preserved renal function (creatinine 1.0 mg/dL; normal range 0.61–1.04 mg/dL) under no particular cardiovascular medications. Immediately after resolving the bradycardia and hypotension, low-dose oral acetazolamide (500 mg/day) and 20% polystyrene sulfate-Ca jelly (Argamate 25 g/day for 3 days) were prescribed to correct the decompensated HF status and electrolyte disturbance. Three days later, both the serum sodium and chloride concentrations had recovered to normal levels (136 mEq/L and 104 mEq/L, respectively), and the serum potassium concentration had decreased to 4.5 mEq/L.
Two weeks later, the patient’s body fluid retention was ameliorated and the serum BNP concentration was near normal (55 pg/mL). Serum chloride and potassium concentrations remained in the normal range, but the serum sodium concentration was slightly reduced (133 mEq/L) compared to that at Day 4 of the hospital admission, which could be managed by changing the diuretic prescription and/or dietary salt adjustment in accordance with the ‘chloride theory’ for HF pathophysiology. Three weeks later, the patient was discharged in an acceptable HF status. Two months later after discharge under the same medication, the patient’s HF status remained stable (serum BNP level of 65 pg/mL) and both the serum sodium and chloride concentrations were normal (139 mEq/L and 108 mEq/L, respectively).
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pmc-6177026-1
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A 71-year-old man was admitted to our hospital with dyspnoea due to severe aortic stenosis complicating a calcified type 0 bicuspid aortic valve. His medical history included diabetes mellitus, atrial fibrillation, chronic respiratory failure, and coronary artery bypass grafting surgery for left main artery stenosis, which uncovered a situs inversus totalis (Figure ). On physical examination the patient had a systolic murmur predominantly located in the second left intercostal space on cardiac auscultation and bilateral crackles regarding the inferior parts of the lungs on pulmonary auscultation. Because of his medical history and a high Society of Thoracic Surgeons (STS) score of 11.9%, the Heart Team recommended TAVI rather than open surgery. The pre-operative multi-slice computed tomography (MSCT) evaluation of the aorta, and its branches confirmed patency of femoral arteries that allowed transfemoral approach (Figure ) and absence of significant thoracic aortic aneurysm.
Pre-operative sizing was performed with the new ValveAssist 2 (Discovery IGS 730, GE Healthcare, Chalfont St Giles, UK) image processing software. Comparatively to the standard fluoroscopy, the new software allows the projection of the MSCT-extracted, manually drawn virtual aortic annulus on the live fluoroscopy screen, and the enhancement of the aortic valve calcifications and aorta calcifications that are used as anatomical landmarks for operator guiding for the positioning of the THV during the procedure (Figures ). A Sapien 3 (Edwards lifesciences, Irvine, CA, USA) 26 mm was directly implanted in a high position (regarding the leaflet extremities rather than the annulus, to reduce the risk of paravalvular regurgitation and need for permanent pacemaker), without post-dilatation, prosthesis constriction and no angiographic leak. The patient did not require permanent pacemaker implantation. A transthoracic echocardiography one week later confirmed an excellent result with no intra or paravalvular regurgitation, and the patient reported improved symptoms. In follow-up consultation 3 months after the procedure the patient reported improved symptoms and had no periprosthetic leak on transthoracic echocardiography.
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pmc-6177029-1
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A 72-year-old man with a history of anteroseptal acute myocardial infarction was admitted to our hospital with acute heart failure. He underwent left ventricular (LV) reconstruction due to LV aneurysm, coronary artery bypass grafting from the left internal thoracic artery to the left anterior descending artery, mitral valvuloplasty with artificial ring for moderate to severe mitral regurgitation, and tricuspid valvuloplasty with artificial ring 18 months earlier. On admission, his blood pressure was 86/55 mmHg, heart rate was 60 b.p.m., and a visible apex beat was present at the 6th left intercostal space just medial to the left mid-clavicular line (, Video S1). Computed tomography revealed a pseudoaneurysm with mild calcification, protruding outside the thorax around the apex of the heart (Figure ). Echocardiogram showed akinesis of the anteroseptal wall and a 40 × 27-mm pseudoaneurysm around the apex of the heart, moving in synchrony with the heartbeat, and a 17% LV ejection fraction (Figure , , Video S2). The connection was confirmed between the pseudoaneurysm and the left ventricle with a spontaneous echo contrast. An underlying infection could have contributed to the formation of the pseudoaneurysm. We theorize that as the pseudoaneurysm progressed, the tissue along its path of progression was mechanically damaged. This gradual damage could have resulted in impaired structural integrity of the surrounding tissue which ultimately allowed certain segments of the heart to protrude into regions beyond the normal anatomical confines of the heart. Left ventricular ejection fraction slightly improved from 17% to 25%, before and after the operation, respectively. The patient was discharged after a protracted hospital course. After discharge, the patient is now coming for follow-ups at regular intervals. Most LV pseudoaneurysm patients present with various clinical observations and abnormal findings on physical examination, such as heart failure, dyspnoea, and chest pain; however, 10% of patients are asymptomatic. In the present case, the pseudoaneurysm protruded into the left thoracic cavity with the pericardium and perforated subcutaneously from the intercostal space. Post-myocardial infarction LV pseudoaneurysm has been reported,; however, a pseudoaneurysm presenting with a visible apex beat is exceptionally rare.
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pmc-6177097-1
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A 22-year-old female patient was referred to the Department of Cardiology with exertional shortness of breath and a history of congenital heart disease with mitral stenosis (MS), VSD and pulmonary hypertension as an outpatient. Five days previously, her condition had deteriorated rapidly, the patient became progressively dyspnoeic and developed orthopnoea, and she was unable to perform daily activities due to severe shortness of breath associated with exertional atypical chest pain. An electrocardiogram showed an ectopic rhythm (78 b.p.m./m), rapid atrial arrhythmias, and a left QRS axis. Upon physical examination, her blood pressure was found to be normal (100/60 mmHg) and the cardiac auscultation showed a 3/6 systolic murmur along the left sternal border. On auscultation of the chest, there were normal vesicular breath sounds. Scoliosis was observed in chest findings. There were no peripheral oedema and jugular venous distention. Blood and biochemical laboratory tests revealed leucocytosis, white blood cell count 10.18 × 109 cells/L (normal value: 3.5–9.5 × 109 cells/L), elevated C-reactive protein levels 25.36 mg/L (normal value: 1–10 mg/L) and NT-proBNP 628 ng/L (normal value: 133–450 ng/L). Chest radiography showed a cardiothoracic ratio of 60%, pulmonary congestion, bilateral pleural thickening and scoliosis.
Next, we performed a transthoracic echocardiography (TTE) that revealed an abnormal membranous structure (1.3 cm × 1.2 cm) attached to the ventricular side of anterior mitral valve (MV) leaflet, with a subaortic chordal attachment. The abnormal tissue was similar to a MV leaflet. The parasternal short-axis view showed the relationship between the normal MV and the accessory valve (Figure ). Therefore, we diagnosed it as AMVT. The peak blood flow velocity across LVOT had accelerated to 5.0 m/s (Figure ). The MV had a parachute-like appearance. There were two normally positioned papillary muscles in the left ventricle, but they did not have chordae tendineae inserted into it. The chordae tendineae were located in the left ventricular wall between the two papillary muscles (). Therefore, we described it as a parachute-like MV. Doppler assessment yielded a peak MV gradient of 27 mmHg and a mean MV gradient of 16 mmHg. Pressure half-time method yielded a valve area of 0.8 cm2. There was also a mild degree of mitral regurgitation. In addition, echocardiography revealed a peri-membranous VSD ( and ) and BAV. The diameter of the VSD was 1.0 cm, and the shunt flow through VSD was left-to-right with a peak velocity of 4.5 m/s. From these findings, we hypothesized that LVOT obstruction was due to the accessory MV, MS was due to PMV and the left-to-right shunt was due to VSD. The pulmonary and tricuspid valves were normal. The pulmonary artery systolic pressure was slightly high (44 mmHg). There was also a mild dilatation of the left atrium (4.2 cm) and left ventricle (left ventricle end-diastolic diameter = 5.2 cm). Systolic function of the left ventricle was estimated to be within normal limits (ejection fraction = 60%). right ventricle function as well as the dimensions and morphology of the aortic arch and the ascending and descending aorta were normal.
In addition, we performed transoesophageal echocardiography (TOE) that confirmed the TTE findings, showing a fixed, membrane-like structure arising from the anterior mitral leaflet causing the LVOT obstruction (). This also confirmed the presence of PMV and VSD ( and ). Transoesophageal echocardiography showed a BAV with only two sinuses: left coronary and right coronary. The right coronary sinus appeared aneurysmal, but not ruptured (). The valve area of BAV was 2.5 cm2 by planimetry, BAV was functioning normally with no aortic valve stenosis or regurgitation.
After a comprehensive clinical evaluation, elective surgical treatment was performed because of the presence of VSD, severity of the MV stenosis and LVOT obstruction. The BAV was functioning normally and was not replaced. The operative findings correlated with the imaging diagnosis. During the operation, excision of the AMV and MV replacement were performed. In addition, the peri-membranous VSD and aneurysm of the aortic sinus were repaired. Grossly, the membranous structure specimens confirmed that it was AMVT (Figure ). Histological examination showed valvular tissue associated with mucous degeneration and inflammatory cell infiltration.
A post-operative echocardiography showed complete resection of AMV, no residual shunt, no left ventricular outflow gradient or mitral regurgitation. The mosaic flow signals in the left ventricular outflow were diminished using colour Doppler, and the peak blood flow velocity decreased to 1.4 m/s. The peak pressure of rapid filling phase and atrial systolic phase across the prosthetic MV were 16 mmHg and 4 mmHg, respectively. The post-operative course was uneventful, and the patient was most recently reviewed 1 week, 1 month, 3 months after the surgical procedure by ultrasound, electrocardiogram, and chest radiography. The function of BAV was evaluated by ultrasound regularly. In the most recent follow-up, the patient’s shortness of breath disappeared, with no further episodes of chest pain.
In this study, we report an extremely rare case of AMVT causing LVOT obstruction associated with PMV, VSD, BAV, and an unruptured aneurysm of the aortic sinus. This combination of symptoms has not been previously reported in literature.
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pmc-6177106-1
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A 43-year-old woman presented with a history of 2 h of central chest pain associated with breathlessness. She had no cardiac risk factors. Her medical history was significant for PE (diagnosed 5 years ago), managed with apixaban, but with poor adherence.
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pmc-6177277-1
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An Assyrian 69-year-old woman born in Turkey was evaluated at our center for a slowly progressive Huntingtonian disorder. Family history was negative. The patient came to Sweden at age 33; she never went to school and learned only a few Swedish words, and could perform simple transactions. She had type 2 diabetes mellitus, bilateral sensorineural hearing loss requiring aids since age 58, and a follicular thyroid tumor, and is a silent carrier of α-thalassemia (table e-1; ).
At age 52 years, the patient developed short memory impairment and increasing difficulties managing activities of daily living. Four years later, she reported olfactory hallucinations and became obsessed with cleaning and doing laundry to remove the perceived foul smells. Perioral movements were documented during an emergency room visit at age 56 for psychiatric issues, and were noted by her family to have been present for many years, predating treatment with aripiprazole. The olfactory hallucinations became so severe that she tried to commit suicide by setting her apartment on fire at age 58. This resulted in admission to a psychiatric unit for a year and treatment with aripiprazole. At age 61, worsened gait, balance, and involuntary movements were evident. For the last 3 years, she has required a walker and reports numbness in her calves. She has lost weight, but there is no evidence of feeding dystonia or dysphagia. Recently, she has become fecally incontinent.
On examination, the patient had chorea in the feet and perioral area, dystonic posturing in the hands and reduced arm movements, a waddling gait, bradykinesia, apraxia, and atrophy of the hand muscles (). A simplified psychometric evaluation demonstrated significant deficits in several domains (table e-2). EEG performed twice was normal; neurophysiologic studies revealed a sensorimotor demyelinating polyneuropathy and myopathy. Muscle biopsy revealed both cytochrome oxidase (COX)–negative and ragged-red fibers. Brain MRI demonstrated atrophy in the left perirolandic frontal and temporal cortex, while FDG-PET showed reduced bilateral hypometabolism in these regions and in the insular cortex, more pronounced on the left side (figures e-1 and e-2; ). An incidental aneurysm in the anterior communicating artery was found and treated conservatively; there was no evidence of brain calcifications on CT scans. Huntington disease (HD) and other HD phenocopies were ruled out (appendix; ). Acanthocytes were found on wet blood smears (figure e-3; ). Whole exome sequencing revealed compound heterozygous variants c.394G>A (p.Gly132Arg) and c.1040C>T (p.Ser347Phe) in the ELAC2 gene (figure e-4; ). ECG was normal but repeated echocardiography demonstrated stable mild ventricular septum hypertrophy without evidence of pump failure. Although we did not find any evidence of respiratory chain defect in the muscle biopsy, the patient's fibroblasts revealed accumulation of unprocessed mitochondrial transcripts but normal steady-state levels of mitochondrial mRNAs and tRNAs (). These fibroblasts showed severe growth impairment when using galactose as energy source (). Treatment with coenzyme Q10 has been started and regular echocardiography is planned.
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pmc-6177337-1
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An 88-year-old man presented with right-sided loin pain and microscopic hematuria, without any urinary symptoms. Routine blood tests revealed derangement of his renal function. An initial ultrasound scan of his urinary tract revealed right-sided hydronephrosis. A further computed tomography of kidneys, ureters, and bladder scan revealed dilatation of the ureter up to the vesicoureteric junction with an associated tight stricture (
). He subsequently had a right rigid ureteroscopy, ureteric biopsy, and ureteric stent insertion. The initial histology was reported as transitional cell carcinoma of the ureter. No neuroendocrine markers were performed at the time, as the tumor did not show any classical signs of a carcinoid tumor or a well-differentiated small cell carcinoma. As demonstrated later, the histology revealed an atypical carcinoid pattern. Further imaging of his chest did not reveal distant metastases and this man underwent a right laparoscopic nephroureterectomy and open excision of bladder cuff.
Macroscopically, the ureter showed a tumor obstructing the lumen toward its distal end, covering a length of ∼18 mm and the resection margin was clear by at least 4 mm. Microscopy of the ureteric specimen revealed a positive immunohistochemical stain with CD56, a common neuroendocrine marker (
). Staining with other neuroendocrine markers was weakly positive (
and
). The tumor was of intermediate to high grade, with a high Ki-67 proliferation index of 25 to 30% (
). Associated carcinoma in situ (CIS) was not seen. There was no definite lymphovascular invasion. The tumor infiltrated through the muscle into the periureteric fat (T3). The background kidney displayed patchy lymphocytic infiltrates in keeping with mild interstitial nephritis. There was no tumor infiltration into the kidney. The urothelium covering the renal pelvis did not show any evidence of CIS or tumor.
The patient made an unremarkable recovery. As he remained well and chromogranin levels were only mildly elevated and stable, the oncologist decided there was no need for adjuvant therapy. Over the past 12 months, his cystoscopies have not shown any signs of recurrence. He also had a repeat computed tomography of his chest, abdomen, and pelvis 12 months postoperatively which did not show any signs of recurrence.
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pmc-6178136-1
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A 72 year old woman was found to have a 2.5 cm nodule in the left thyroid. Thyroid function tests were within the normal range. She had no family history of thyroid or other endocrine disease. Her medical history was unremarkable. A fine needle biopsy of the lesion was diagnosed as “suspicious for neoplasm.” She underwent left hemithyroidectomy.
The tumor was diagnosed as papillary thyroid carcinoma by the pathologist at the originating institution. There was extrathyroidal extension. A consultation from a thyroid expert confirmed the diagnosis. The patient was referred to our institution for completion thyroidectomy and radioactive iodine therapy. Pathology review was requested.
The patient was evaluated for metastatic disease and none was identified. She is alive and well with no evidence of recurrence 18 months later. The patient provided informed signed consent for publication of her data.
The thyroid contained an infiltrative tumor that had areas of follicular and papillary architecture but the overall morphology and cytologic features were atypical for a tumor of thyroid follicular differentiation. The surrounding thyroid exhibited chronic lymphocytic thyroiditis. The tumor was composed of solid sheets and nests in a fibrovascular stroma (Figure ) with cribriform areas, microcysts, cleft-like structures, and focal pseudopapillae with a few true papillae (Figure ). The tumor cells were relatively homogeneous with abundant eosinophilic cytoplasm and monotonous round nuclei with clear nucleoplasm and conspicuous large nucleoli but no indentations or inclusions (Figure ). There was frank extrathyroidal extension into surrounding skeletal muscle (Figure ). In one area of the tumor there was a small 0.2 cm focus of classical papillary microcarcinoma with the distinctive features of that entity that were clearly different from the rest of the lesion (Figure ).
Immunohistochemistry of the dominant tumor identified diffuse but weak monoclonal PAX-8 nuclear reactivity (Figure ) but TTF-1 (clone: SPT24) was only focal and weak (Figure ) and thyroglobulin staining was completely negative (Figure ). Stains for Cytokeratin 7 and Cytokeratin 19 (Figure ) were diffusely positive but Cytokeratin 5 was only focally expressed. Although polyclonal CEA was positive (Figure ), monoclonal CEA was negative, as was synaptophysin and chromogranin-A. Scattered tumor cells were positive for gross cystic disease fluid protein-15 (GCDFP-15) (Figure ), some stained for p63 (Figure ) and stellate cells were identified by localization of S100 protein (Figure ). CD5 positivity was restricted to infiltrating lymphocytes. Beta-catenin (Figure ) and E-cadherin (Figure ) positivity was intact at the tumor cell membrane and there was no nuclear translocation.
The diagnosis was changed to Mammary Analog Secretory Carcinoma (MASC), an unusual tumor of salivary gland, associated with a 0.2 cm papillary microcarcinoma.
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pmc-6178147-1
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Miss S, a 19-year-old woman, presented to antenatal clinic at 19 weeks gestation for a first consultation because of a preexisting hepatocyte nuclear factor α (HNF-1α) mutation causing MODY 3 diabetes. The patient was well known to the paediatric endocrinology and diabetes services since age of 11 years when her condition first became apparent through recurrent mucosal candidiasis and mild postprandial hyperglycaemia. Due to a strong family history of diabetes () and negative testing for type I diabetes, an HNF1α gene mutation was suspected and subsequently confirmed on molecular genetic testing. Interestingly, in addition to a known pathogenic mutation, she also had a second missense variant in HNF1α of uncertain clinical significance (). The patient was initially successfully treated with the sulfonylurea (SU) gliclazide, which more recently was switched to insulin due to increasing hyperglycaemia.
The father of the fetus is a 21-year-old man also well known to endocrinology and diabetes teams from age of 9 years, due to persistent mild hyperglycaemia and very significant family history of diabetes (). Genetic testing for a Glucokinase (GCK) mutation was performed and confirmed the presence of MODY 2 diabetes (). Following diagnosis, as anticipated, the father remained asymptomatic and did not require any further treatment.
Prenatally, given the autosomal dominant inheritance pattern of MODY, the inheritance possibilities were calculated as follows: 25% chance of being healthy without any form of MODY, 25% chance of having MODY 2 only, 25% chance of having sole MODY 3, and 25 % chance of having compound heterozygous mutations for both MODY 2 and MODY 3. From a pregnancy point of view, a plan was made for biweekly growth scans starting at 24 weeks of gestation and to review the patient fortnightly in combined obstetric and diabetes clinic. Pregnancy targets are individualised in this clinic, but in general aim for fasting glucose <5mmol/L; 2 hour postprandial <6.7mmol/L. She was managed with insulin glargine (Lantus®) daily and insulin aspart (Novorapid®) with meals, and insulin requirements gently increased over the pregnancy, from approximately 0.75 units/kg/day early pregnancy to 0.83 units/kg day at 28 weeks.
Despite this relatively small increase in dosing, her HbA1c fell from a pre-pregnancy value of 68mmol/mol (8.4%) to 45mmol/mol at 18 weeks, and 35mmol/mol at 28 weeks. From 28 weeks, doses were further reduced, until she presented to the emergency department at 33+3 weeks of gestation for frequent hypoglycaemia. She was admitted to the antenatal ward and her insulin was gradually reduced from an approximate total daily insulin dose 0.65 units/kg/day to glargine 4 units and 1 unit of aspart per 18g of carbohydrates with meals (total daily dose approximately 0.28 units/kg/day). Given the significant fall in insulin requirement, concerns were raised that this might be due to a failing fetoplacental unit. Against this, the patient never developed hypertension, and laboratory screening for preeclampsia was performed multiple times and was always within normal limits.
Fetal growth until this presentation had been measured by fortnightly ultrasound and was on the 50th centile of the Australasian Society of Ultrasound in Medicine (ASUM) growth charts. Given the unknown significance of the falling insulin requirements, biweekly monitoring of fetal wellbeing via Doppler measurements was commenced, which was satisfactory at all times. The patient received 2 doses of intramuscular Betamethasone 11.4 mg intramuscularly for lung maturation. At 34+3 weeks of gestation the patient went into spontaneous labour and delivered a healthy baby girl via forceps, weight 2.22kg, APGARs 7, 9, and 10 (at 1, 5, and 10 min, respectively). Histological examination of the placenta was not performed. Due to prematurity, the baby was admitted to the neonatal intensive care unit and was discharged home at 36+1 weeks of life. Postnatal genetic testing in the baby showed a heterozygous mutation for the maternal familial likely nonpathogenic HNF1A gene variant (), which has been reported in the literature with two functional studies and found to be of uncertain clinical significance [, ]. Importantly, both parental known pathogenic mutations were absent.
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pmc-6178166-1
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A 37-year-old Caucasian male with a past medical history of alcohol abuse was referred for inpatient admission after being found to have pancytopenia. He had subjective fever and productive cough with yellow sputum a few weeks ago, which resolved after a few days without treatment. He visited his primary care physician and laboratory exam showed pancytopenia, thus leading to the referral. He also endorsed generalized weakness, progressive right eye blurry vision, and chest tightness for the past few weeks. There was no skin rash, joint pain, hair loss, heartburn, and Raynaud's phenomenon. Physical exam was only remarkable for cervical nontender lymphadenopathy.
Upon admission, he was febrile with a maximum temperature of 101.2 F. Laboratory exam was notable for white blood cell 1,900 counts/μL, hemoglobin 7.2 g/dL, hematocrit 21.2%, platelet 19,000 counts/μL, sodium 126 mmol/L, and creatinine 1.44 mg/dL. Urinalysis showed elevated white blood cells, dysmorphic red blood cells, and proteinuria. Further work up showed that he had elevated ferritin 6542 ng/mL, high triglycerides 327 mg/dL, marked decreased complement levels (C3 14 mg/dL and C4 3 mg/dL), elevated ESR 137 mm/hr, strongly positive for antinuclear antibody (ANA, 1 : 640), and anti-double-stranded DNA antibody (anti-dsDNA, >1 : 1280). Anticardiolipin antibody (IgM and IgG) and beta-2 glycoprotein I antibody (IgG) were also positive. Direct antiglobulin test (Coomb's) was positive. Urine studies showed microalbumin to creatinine ratio of 1958 mg/g and protein creatinine ratio of 7.04 mg/mg consistent with nephrotic-range proteinuria. Transthoracic echocardiogram showed normal ventricular function but moderate circumferential pericardial effusion. Abdominal ultrasonography showed hepatosplenomegaly with evidence of cirrhosis. Based on the above findings, he was diagnosed with systemic lupus erythematosus, pericarditis, and lupus nephritis. Pulse steroid with methylprednisolone 1000 mg daily was started for 3 days, followed by oral prednisone 60 mg daily. His fever and chest pain resolved, and his blood cell counts and creatinine improved after the treatment. He subsequently underwent bone marrow biopsy which showed increased histiocytes with focal evidence of hemophagocytic cells consistent with macrophage activation syndrome considering his clinical presentation. Renal biopsy was also performed and confirmed diffuse proliferative and membranous lupus nephritis (Class IV/V) along with focal segmental glomerulosclerosis NOS type. He also underwent ophthalmology evaluation, and funduscopic exam with fluorescein angiogram showed cotton-wool spots with retinal hemorrhage consistent with retinal vasculitis. His laboratory examination continued to improve, and he was subsequently discharged from hospital one week after admission. Mycophenolate mofetil was started in addition to steroid upon discharge. Repeat transthoracic echocardiogram three weeks after treatment showed marked decrease in pericardial effusions. His disease remained stable while on mycophenolate mofetil with prednisone gradually tapered from 60 mg to 10 mg twelfth week after discharge. His vision acuity remained stable, and repeat funduscopic examination showed improvement of his retinal lesions. Detailed laboratory examination in the hospital and on follow-up visit is presented in .
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pmc-6178167-1
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A 74-year-old male outpatient had been undergoing treatment for RA since 2000 and began taking the biological product tocilizumab in 2014. This treatment was stopped in 2015 because of excreted Mycobacterium intracellulare in the sputum. He was admitted to our hospital because of breathing difficulty in May 2016. A chest computed tomography scan showed pneumothorax and pleural effusion in the right lung and a main cavity lesion in the right upper lobe (). A laboratory culture from the sputum and pleural effusion was positive for M. intracellulare, and we arrived at a diagnosis of secondary pyopneumothorax caused by M. intracellulare. The changes in the C-reactive protein (CRP) concentration are shown in . Despite multidrug therapy and thoracic drainage for the pyopneumothorax, air leakage persisted. We planned endoscopic bronchial occlusion therapy because surgical therapy carried a high risk for the patient (his performance status at the time was 2). This technique was performed in the right B2 bronchus for the first session on day 11 (Figures and ), but it did not completely stop the air leak. Therefore, we performed the second session in B1b on day 32 after onset (Figures and ). Following the second treatment, although major air leakage was not observed a minor air leak persisted for some time, eventually stopping on day 99. Thereafter, thoracic drainage was continued because of the prolonged purulent discharge [a laboratory culture of the pleural effusion was negative for M. intracellulare on day 138, whereas it had been positive for methicillin-resistant Staphylococcus aureus from day 87 to day 228 (the final examination day)]. The purulent discharge was then reduced, the thoracic drain was removed on day 263, and the pyopneumothorax improved. At the time of the present writing (>2 years after the procedure), the patient was undergoing follow-up on an outpatient basis.
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pmc-6178180-1
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A 49-year-old Caucasian woman presented to the emergency room with three-day history of palpitations, shortness of breath, pallor, and black tarry stools. She was found to be anemic with hemoglobin of 4.4 g/dL. She was transfused, and a gastrointestinal bleeding workup was initiated. The rest of the physical examination and additional blood tests were within normal limits. A computed tomography (CT) scan of the abdomen showed a possible hypodense mass in the second/third portion of the duodenum that is intraluminal with an extraluminal component abutting the uncinate process of the pancreas. There was no sign of any other disease in the abdomen and lower chest (). Colonoscopy was negative, and upper endoscopy showed an ulcerated mass in the second/third portion of the duodenum worrisome for duodenal adenocarcinoma (). The mass was not bleeding at the time of the endoscopy. A biopsy of the mass done during endoscopy was inconclusive and showed cellular debris. The patient stabilized and stopped bleeding and was discharged home. She was electively seen at the hepatobiliary surgery clinic where additional staging workup was negative, including tumor markers. The patient's personal and family history were noncontributory. A pancreaticoduodenectomy was recommended based on the suspicion for a duodenal adenocarcinoma and was successfully performed. She had an uneventful hospital stay and was discharged home on postoperative day five. Her final pathology revealed a duodenal gangliocytic paraganglioma eroding into the pancreas, and all lymph nodes were negative for tumor. She was seen eight months postoperatively and was still free of disease.
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pmc-6178186-1
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A 22-year-old Turkish-origin male with a past medical history of Cystic Fibrosis presented with a one-day history of right lower quadrant abdominal pain. He described sharp periumbilical pain that continued to worsen which then shifted to right lower quadrant abdomen. Prior to the onset of the abdominal pain, he reported experiencing nausea and anorexia for three days. His last bowel movement was two days prior to admission. The patient was diagnosed with Cystic Fibrosis at the age of four and his disease progressed to exocrine pancreas insufficiency, which was being treated with pancreatic enzymes. Upon reviewing the patient's past history, it was noted that he had several episodes of pneumonia for which he was appropriately treated with antibiotics; notably, no history of constipation or recurrent abdominal discomfort was reported prior. At home, the patient was prescribed Albuterol inhaler as needed, Dornase Alfa inhaler, Aztreonam lysine nebulization, Azithromycin 500 mg three times a week, Lansoprazole, Lumacaftor-ivacaftor twice a day, Lipase-protease-amylase capsule three times a day, and a multivitamin capsule once a day. On abdominal exam, he had diminished bowel sounds and tenderness on right lower quadrant with equivocal rebound tenderness. Laboratory analysis showed leukocytosis (WBC 13.0 mm/K3, Neutrophils 62%) with a normal differential. He had no electrolyte imbalances. Computed Tomography (CT) of the Abdomen revealed thickening and edema around the terminal ileum, a colon with inflammatory changes, free fluid in the right paracolic gutter adjacent to the cecum, an appendix measuring 5.3 × 4.6 mm, and reactive lymph nodes (Figures and ). Due to extraluminal fluid and cecal wall edema with inflammation, early acute appendicitis could not be excluded as a diagnosis. Surgical intervention was performed which revealed a ruptured microperforation of a cecal diverticulum and a distended appendix in chronic adhesions for which he required an appendectomy and partial cecectomy with intact ileocecal valve (IC valve). Postoperatively, he was diagnosed with DIOS and subsequently started on Polyethylene Glycol. The patient made an unremarkable recovery and was discharged home to be followed up in the outpatient clinic without any recurrence of any symptoms.
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pmc-6178251-1
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A 19-year-old Pakistani/Asian man with a low socioeconomic background was brought to the emergency department of our hospital with a 15-h history of altered behavior, acute confusion, and disturbed gait. His family did not report any fever, recent fall, accident, or substance abuse. His parents had died at a young age, and he was living with his paternal uncle. He used to work in a generator shop, and he had a history of occasional alcohol and cannabis intake and benzodiazepine abuse 6 months earlier.
On presentation, his blood pressures was 148/65 mmHg with a regular heart rate 96 beats/min. His oxygen saturation was normal, but his breathing was rapid and deep at a rate of 32/min. His temperature was recorded at 36.8 °C. On examination, he was found to be very agitated and was not comprehending. His neck was supple, and his examination result was negative for Kernig’s and Brudzinski’s signs. He was moving all four limbs symmetrically and withdrawing from painful stimuli. His tendon reflexes were normal bilaterally, and his plantar responses were downward. His pupils were normal in size and equally reactive to light. The results of his chest, abdominal, and cardiac examinations were within normal limits.
Laboratory investigations showed serum anion gap 28 mmol/L, osmolal gap 22.5 mOsmol/kg, arterial pH 7.23, lactate 15 mmol/L, potassium 5.6 mmol/L, sodium 140 mmol/L, bicarbonate 5.8 mmol/L, random blood sugar 108 mg/dl, serum blood urea nitrogen (BUN) 7 mg/dl, serum creatinine 1.3 mg/dl, hemoglobin 17 g/dl, white blood cell count 24.4 × 109 (neutrophils 82%), platelets 447 × 109, negative urine toxicology screen (amphetamine, cannabinoids, barbiturates, benzodiazepines, opiates, and cocaine), and negative serum ethanol. Serum methanol levels were not measured, because the assay was not available. urinalysis demonstrated 2+ proteins, 1 white blood cell, 10 red blood cells, 5+ hemoglobin, no cast, and no crystals. The results of amylase, lipase, creatinine phosphokinase, and liver function tests, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, were within normal ranges. Blood and urine culture results were negative.
The patient’s chest radiography result was normal. His electrocardiogram showed sinus tachycardia. Ultrasound of his kidneys revealed bilateral swollen kidneys. Computed tomography (CT) of his head showed cerebral edema.
At that point, our differential diagnosis included acute methanol or ethylene glycol poisoning (on the basis of high anion gap metabolic acidosis; elevated osmolal gap; and history of substance abuse in the past, though there was no history of intake) and septic encephalopathy (acute confusional state with raised white blood cell count).
In the presence of severe metabolic acidosis and acute kidney injury, the patient was started on an intravenous diluted sodium bicarbonate infusion along with intravenous crystalloids. Empiric intravenous ceftriaxone was initiated.
During the first 24 hours of admission, the patient showed remarkable improvement in his consciousness level; however, he was still delirious but started following commands. His serum bicarbonate improved to 18 mEq/L, and his white blood cell count decreased. Although his urine output was adequate at approximately 1.2–1.5 L/d, his serum creatinine worsened. The family and the patient were questioned again regarding intake of methanol or ethylene glycol, but denied it completely.
On day 3 of admission, the patient confessed taking transformer oil in order to commit suicide. The transformer oil had been kept in their home for more than 1 year and was collected from a burst transformer. On subsequent days, after an initial improvement, the patient’s consciousness level deteriorated rapidly, and he started complaining of continuous headache with episodes of increased agitation alternating with acute delirium. Despite an adequate urine output and normal electrolytes, his serum creatinine kept on worsening.
At that time, his consciousness level was not explained by uremia, because his BUN was only 50 mEq/L, though his creatinine had risen to 8.5 mg/dl. Hemodialysis was considered at that point, but our suspicion was intake of some lipophilic substance that could not be dialyzed. Because of the patient’s unexplained delirious state, CT of the head was repeated, which revealed abnormal low-density areas in bilateral temporal, parietal, and occipital lobes; genu of corpus callosum; and right cerebellar peduncle along with cerebral edema.
On day 7, the patient’s urine output declined, and his BUN and creatinine increased to 80 mg/dl and 12.5 mg/dl, respectively. He had two episodes of generalized tonic-clonic seizures and was dialyzed immediately for 4 hours. After the first hemodialysis session, although the patient’s BUN fell only slightly from 80 to 60 mg/dl, he showed a remarkable improvement in his consciousness level. He became calm and alert, his agitation was almost alleviated, and his complaints of headache became less frequent. He was again dialyzed consecutively for the next 2 days.
After three consecutive sessions of hemodialysis, no further dialysis was needed. The patient’s headache subsided completely, and his consciousness level improved significantly, which further pointed to removal of certain substances via dialysis as the cause of altered sensorium and kidney injury. He was discharged on day 12 with stable serum creatinine, which was completely normalized 10 days after discharge. The patient is under regular follow-up, and his renal function is normal. The trend of the patient’s renal function is shown in Table .
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pmc-6178258-1
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An 18-year-old Japanese woman visited our hospital with a chief complaint of gingival swelling in the region of her upper right anterior teeth, midline diastema, and tooth crowding. Her main symptom was gingival swelling in the region of her upper right anterior teeth. She had no medical, family and psychosocial history, and she had not undergone relevant past interventions. A physical examination showed no problems. She had previously undergone root canal treatment for the remaining deciduous canine because of pus discharging from the root canal. An intraoral examination revealed a diffuse swelling around the deciduous canine, midline diastema, and tooth crowding. A panoramic radiograph revealed a round radiolucency with a diameter of 30 mm, with well-demarcated margins around the maxillary canine (Fig. ). Computed tomography (CT) revealed that the cystic cavity surrounded the maxillary canine and was filled with a homogeneous water-like fluid with density (Fig. ). Our clinical diagnosis was maxillary dentigerous cyst with an unerupted maxillary canine. Marsupialization was carried out under general anesthesia, and the unerupted canine was left in place (Fig. ). A histopathological examination revealed the diagnosis of dentigerous cyst. However, the marsupialization did not result in eruption of the canine. Three months later, orthodontic traction was applied to the unerupted canine, and simultaneously orthodontic treatment to correct the tooth crowding and midline diastema (Fig. ). The orthodontic traction of the maxillary canine failed, and the canine was then extracted. On the other hand, crowding and midline diastema were improved (Fig. ). The revised treatment plan was to undertake staged implant placement, because the alveolar bone at the implant site was inadequate, 2 mm alveolar width on CT (Fig. ). We were planning to bone graft after the mucosa completely healed up because severe scar tissue caused by the previous marsupialization was seen in the canine tooth extraction area. Bone augmentation was performed with an autogenous bone graft that was harvested from the mandibular ramus to widen the alveolar bone (Fig. ). While doing the implant placement in the second operation, a part of the grafted bone was exposed, and was trimmed with a bur, several times (Fig. ). The wound had completely healed up in 6 months. For her busy schedule, 11 months after the bone graft, the implant was inserted without any problems. The implant was uncovered, and the abutment was connected under local anesthesia (Fig. ). The occlusion was stabilized by the implant, following a screw-retained prosthodontic procedure performed with appropriate implant stability. The occlusion was successfully restored by the insertion of the implant (Table ). Good clinical results were achieved with no severe complications or recurrence of the cyst (Fig. ). Her postoperative course was uneventful for 7 years. A CT scan taken 7 years after marsupialization showed that the cystic cavity had been replaced by new bone, and that the implant was stable in the surrounding bone (Figs. , ).
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pmc-6178272-1
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This male infant was the second child of a 39-year-old mother and was born via cesarean section during the 38th week of the pregnancy with a birth weight of 3300 g. The infant was admitted to our hospital 10 days after birth due to pneumonia and was treated with meropenem. He developed abdominal distension and diarrhea gradually from the 10th day of therapy on and stool culture revealed a Clostridium difficile infection. This was considered to be antibiotic-related and oral metronidazole and vancomycin were given. His symptoms were soon resolved but after discharge he gradually developed abdominal distension and constipation. A barium enema exam on the 42nd day after birth showed stenosis at the junction of the sigmoid and descending colon and a distended proximal bowel (Fig. ). Abdominal distension and constipation became more severe after 3 weeks of conservative treatment. A second barium enema exam then revealed another stenosis of the right transverse colon in addition to the previous stenosis (Fig. ).
Primary surgical exploration revealed two segments of stenoses. One was at the junction of the sigmoid and descending colon and was 3.5 cm in length, while the other one was at the right transverse colon and was 4 cm in length. The small intestine, however, was still intact. Both the two parts were resected and an ileostomy was conducted at the terminal ileum. A pathological exam showed fibrosis of lamina propria in the narrow segments. Ganglion cells were normal (Fig. and ). Closure of ileostomy was performed 3 months later and he made uneventful recovery. At the 1-year follow-up, he exhibited a normal dietary intake and defecation. His state of growth and development was in the 70th percentile.
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pmc-6178332-1
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CASE 1: the first case was a 28- year-old female with MDD (depressed mood, weight loss, and psychomotor retardation, loss of energy, and insomnia for more than 1 month). She was started on 75mg sertraline daily but started to suffer from bruxism and jaw spasm in the second week of receiving the medication. She stopped taking sertraline because of its side effects and immediately visited a psychiatrist because of her depression and bruxism. Again, she was prescribed 75mg sertraline and 25mg quetiapine. Her bruxism improved after 5 days, and she remained symptom- free throughout the following month.
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pmc-6178332-2
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CASE 2: the second case was a 35- year-old male with episodes of MDD during last 5 years and suffered some side effects, such as akathisia, restlessness, bruxism and mandibular dystonia, after taking sertraline. He discontinued the medication due to the side effects. Then, he was prescribed sertraline 12.5 mg daily and the dose was increased to 50 mg daily. However, after a week, he began to suffer from bruxism and mandibular dystonia. Thus, he started taking quetiapine (25 mg one time at night) and his condition improved after 5 days and continued taking SSRI drug for his major depressive disorder.
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pmc-6178332-3
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CASE 3: the third case was an 18-year-old female with MDD during last 2 months, with depressed mood, restlessness, diminished ability to concentrate, fatigue, and insomnia. She was prescribed with fluoxetine (20 mg daily), but shortly after the onset of drug treatment, she developed bruxism. She improved significantly after one week by taking quetiapine 12.5 mg in the morning and 25 mg at night, and she completely improved after 3 weeks.
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pmc-6178332-4
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CASE 4: Our fourth case was a 45-year-old female with MDD (depressed mood, significant weight loss, insomnia, fatigue, and feeling of worthlessness, diminished interest in all activities most of the day for more than 1 month). She started sertraline 12.5 mg daily and had good drug compliance. Three weeks after sertraline dose was increased to 50 mg daily, she developed bruxism, lip movements, and jaw dystonia. She received quetiapine (12.5 mg in the morning and 25 mg at night) and, as a result, her condition improved after 5 days, and she remained symptom-free throughout the following month.
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pmc-6178332-5
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CASE 5: Our fifth case was a 32-year-old female with postpartum depression 5 years ago. She had been admitted to the hospital due to suicidal ideas at that time. She received ECT and citalopram, clonazepam, and quetiapine, and her condition improved completely. She had no psychiatric problems for the last 5 years up to 2 months ago when she showed restlessness, sleep problems, depressed mood, decreased social function, and suicidal ideas. We recommended hospitalization because of her MDD diagnosis, but she disagreed, so we started her on citalopram (10 mg daily) and clonazepam (1 mg daily) in an outpatient setting. Two weeks after starting the medication, she showed partial improvement. The patient suffered from bruxism and, thus, was prescribed quetiapine (25 mg daily); and 10 days after taking quetiapine, she reported no bruxism and continued taking citalopram.
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pmc-6178507-1
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The patient is an African-American female born at 37 weeks six days gestation to a 19-year-old mother. She was noted to have a 1.5 cm pedunculated soft tissue mass with adjacent secondary 8 mm mass on the oral mucosa along the mandibular alveolar ridge ().
Due to difficulty with breast-feeding, decision was made for operative excision on the third day of life. In the operating room, she received general anesthesia with oral endotracheal intubation ().
Local anesthetic of 0.6 cc 0.5% lidocaine with 1 : 200,000 epinephrine was administered at the base of the masses. Excision was performed sharply with scalpel and hemostasis with bipolar electrocautery. Complete closure of the defect was not possible, but was reapproximated to near closure with 5-0 chromic sutures in simple interrupted fashion in a crosshatched pattern ().
She was allowed to return to breast and formula oral intake postoperatively on the same day. She was monitored for two days and then discharged home. Follow-up after three weeks revealed well-healed mucosa at the surgical site with minimal notching on the alveolar ridge and no evidence of recurrence ().
Microscopic pathology confirmed squamous mucosa with underlying large polyhedral cells containing granular acidophilic cytoplasm as well as small hyperchromatic nuclei, staining negative for S-100 immunohistochemistry, with extension to the excisional base of the lesion. Centrally dilated blood vessels were seen with mild nonspecific chronic inflammatory changes as well as prominent nucleoli in some cells. No dysplasia or malignancy was noted centrally or peripherally. All microscopic findings appear consistent with that of CGCT.
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pmc-6178765-1
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Patient 54, a 12-year-old male with a history of cutaneous bleeding and a mild reduction in platelet count (101 × 109/L) was noted with a stop loss variant in GATA1; c.1240T>C, p.*414Arg+41. The predicted effect of variation is a loss of the wild type stop codon and extension of the protein by 41 amino acids. Most reported variants within GATA1 occur within the N-terminal zinc finger domain, leading to a disruption of the binding of GATA1 to FOG1. The stop-loss variant noted in patient 54, was first identified in a 67-year-old male proband who suffers from easy bruising. The patient's platelet counts varied between 86 to 94 × 109/L at different times of testing and no other differences in hematological cell numbers were noted. The patient was initially sequenced due to the presence of a rare X-linked blood group Lu(a-b-) phenotype which results in the marked decrease in expression of Lutheran glycoprotein on the erythrocyte cell surface. To date, serological analysis using flow cytometry to analyze the presence of Lutheran on the erythrocyte cell surface has not been undertaken in patient 54. Also the presence of giant occasional macrothrombocytes, a marker of the published phenotype, have not been observed in patient 54 in routine histological examination.
A previously identified causative variant was noted in RUNX1 in patient 59. The missense variant, c.386C>A, p.Ala129Glu, was found in addition to a missense variant in ITGA2B. The variant has previously been reported to be causative of FPD/AML in three patients from a single pedigree. All three patients were identified with the p.Ala129Glu germline mutation causative of FPD/AML. All patients developed AML as a result of a secondary somatic event occurring within RUNX1 progressing to patient death in all cases. Patient 59 is a male with a mild reduction in platelet count to 94 × 109/L. Following platelet function testing no reduction in platelet secretion (a hallmark of variants within RUNX1) was noted. However, it is highly likely that the variant observed in RUNX1 is causative of the hemostatic phenotype observed. Whether the variant within ITGA2B is additive to the phenotype is unlikely as the platelet count is considered mild in severity but may warrant further investigation.
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pmc-6178905-1
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A four-year-old Egyptian boy presented to the Pediatric Dental Clinic, Faculty of Dentistry, Cairo University, suffering from premature loss of anterior teeth, friable and bleeding gums and swelling related to the upper anterior region. Medical history revealed absence of any medical problems; family history revealed that neither parents nor siblings had the same problem and the parents were not of consanguineous marriage.
Examination of the palms of the hand revealed normal skin, while the soles of the feet revealed very slight hyperkeratosis (
). Intraoral examination revealed severe gingival recession; inflammation especially in anterior region; aggressive periodontitis; mobility of maxillary left central incisor and canine, with swelling related to the maxillary right missed canine region extending toward occlusal surface. The swelling appeared as a solitary rounded lesion, with onset gradual for 2 months. The size of the swelling was 4×4 mm, and upon palpation it was not tender but slightly hemorrhagic (
).
Radiographic examination showed severe destruction and loss of alveolar bone (
). Lab investigations were normal (
).
Taking into consideration the clinical features and investigations, a diagnosis of PLS was confirmed.
Conventional periodontal treatment in the form of scaling and root planning was performed. Antibiotic amoxicillin and metronidazole (250 mg, 3 times daily) for one week along with a mouth rinse (0.2% chlorhexidine gluconate, 10 mL twice daily) was prescribed to the patient
.
Extraction of the maxillary left central and canine teeth was advised, but the parent refused even after the risk was explained of not extracting these loose teeth.
After laboratory investigations, excisional biopsy of the swelling was done under antibiotic coverage and local anesthesia. Thorough curettage of the adjacent periodontal ligament and periosteum was carried out to prevent recurrence (
). Histopathological examination revealed the lesion as peripheral ossifying fibroma (
).
The patient was educated for oral hygiene and scheduled for a follow-up visit every month for scaling and checking the condition of the patient.
The patient was followed up for 2 years during which loss of maxillary left central incisor occurred and extraction of loose upper left canine was done with no recurrence of the lesion (
). The palms of the hands revealed no change, while examination of the soles of the feet showed slight increase in keratosis (
).
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pmc-6178910-1
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A 66 year old African-American male presented to the Emergency Room (ER) complaining of a 2-hour history of chest pain. Chest pain was described as left-sided, non-pleuritic, non-radiating, retrosternal, squeezing in character and persistent. Pain was reported as 9 on a 10-point pain scale and relieved by taking 0.4mg tablet of nitroglycerin sublingually. It was associated with shortness of breath, dizziness and sweating, but the patient denied loss of consciousness, cough, palpitation or swelling of the extremities. He denied any use of illicit substances. A week prior to this hospitalization he presented to the hospital with a similar complaint. At that time, chest pain was relieved by 325mg dose Aspirin taken orally; troponin was normal and EKG did not show any significant change from baseline. His echocardiogram was also normal and he was discharged with scheduled outpatient stress test. Medical history was significant for poorly-controlled diabetes type 2, hypertension, dyslipidemia and obesity.
On this visit, his pulse rate was 84 beats per minute; BP 119/66 mm/Hg; respiration rate 16 breaths per minute and his oxygen saturation was 98% on room air. Initial troponin was elevated at 0.19ng/ml (reference 0.00 – 0.05ng/ml); hemoglobin of 14.4g/dl (reference 13–17g/dl) and platelet count of 210 × 10
3/ul (reference 130–400 × 10
3/ul).
EKG showed deep T wave inversions in leads V1–V6 and the inferior limb leads (
). We assumed an assessment of non-ST elevation myocardial infarction and a loading dose of Aspirin (325 mg) and Plavix (300 mg) were given orally in the ER along with Atorvastatin (80 mg) and a weight-based dose of Enoxaparin. Repeat troponin 6 hours later was 1.05. Cardiac catheterization revealed normal coronaries (
). While the patient was still lying on the cardiac cath table, his oxygen saturation dropped to 91%. There was no chest pain, tachypnea or tachycardia at this time. Supplemental oxygen at 2l/min via nasal cannula improved saturation to 97%. A repeat EKG showed a Q
3T
3 pattern in lead III (
). In view of these new findings (low oxygen saturation and a change in the EKG pattern), a computerized tomography of the chest with angiogram (chest CTA) was ordered. This revealed a saddle pulmonary embolus which extended into the right and left pulmonary arteries and involved all lobar branches of the pulmonary arteries (
).
Treatment was continued with Enoxaparin (100mg subcutaneously every 12 hours) for 6 days, at which time he became stable and maintained oxygen saturation above 96% even when supine. He was discharged on Apixaban (10mg po bid for 7 days followed by 5mg po bid) with plan to complete 3 months of therapy. Follow up visits were scheduled with the Cardiology and Hematology clinics.
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pmc-6179062-1
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A 46-year-old male, right hand dominant, information technology manager, was referred to clinic with a flexor tendon deficit in the right little finger.
He described an onset of pain and cramping within the palm, whilst pulling open a door with his right hand. The pain instantaneously resolved but he was left with an immediate inability to flex the right little finger at the distal interphalangeal joint (DIPJ). Prior to this, he had not experienced any difficulty or discomfort on flexing this finger. The patient denied any history of trauma or previous injections in the hand or wrist. He was otherwise healthy and a non-smoker. Blood tests and radiographs were unremarkable ().
On clinical examination, there was no bruising but there was slight tenderness along the 5th finger and distal palm and he was unable to flex his DIPJ. A closed FDP tendon avulsion injury, at the bony insertion, was suspected and surgical exploration and repair was planned.
Intra-operatively, the FDP tendon was found to be intact in Zones I, II and III. Despite this, the tendon was lax with absence of tenodesis effect. The wrist was explored next on the suspicion of rupture at the musculotendinous junction.
FDP was found to be intact but lax and was not activating the distal FDP tendon. The carpal tunnel was then explored, eventually identifying the FDP rupture site at the origin of the lumbrical muscle. There were no signs of synovitis or attrition and no sharp edges within, the carpal tunnel (). Except for the rupture site, the tendon substance and lumbrical muscle were normal. The rupture was repaired with a four-strand core Adelaide repair using 3/0 Prolene and simple running epitendinous repair with 5/0 Prolene.
Postoperatively, the patient underwent early active motion flexor tendon protocol with our hand therapy department. At three and six month follow up review, the tendon remained intact, he had regained his full range of motion and reported normal, pain free, grip strength ( and ).
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pmc-6179972-1
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A 40-year-old man presented with redness, pain, and decreased vision in the right eye 1 day following cataract surgery done elsewhere. The patient had received intravitreal antibiotics (ceftazidime and vancomycin) prior to referral to us. His corrected distance visual acuity (CDVA) was light perception with accurate projection of rays. Slit lamp biomicroscopy of the anterior segment showed cloudy cornea with ring infiltrate and pinkish hypopyon along with congested, chemosed conjunctiva (Fig. ). B-scan ultrasonography showed multiple hyperechoic areas with the attached retina (Fig. ). Anterior chamber wash, with intravitreal imipenum (50 mg/0.1 mL), ceftazidime (2.25 mg/0.1 mL), and dexamethasone (400 μg/0.1 ml), was given. There was a delay in sending the sample to the microbiology laboratory by 16 h. Gram stain of the vitreous biopsy showed filamentous very long gram-negative bacilli, with doubtful branching (Fig. ) which was non-acid fast. The initial impression was that of actinomycetes although the gram-negative staining was contradictory. The next day, culture showed growth of greenish-gray moist colonies, which was identified as Pseudomonas aeruginosa. The organism was resistant to tobramycin, tigecycline, chloramphenicol, gentamicin, and moxifloxacin and was susceptible to colistin, ciprofloxacin, and ceftazidime as shown in Table . Systemic treatment included oral ciprofolxacin (750 mg BD) and oral prednisolone (4 mg/0.1 ml). Lack of clinical improvement necessitated intravitreal injections of ceftazidime and triamcinilone twice over. Once the exudates cleared, the patient was given systemic steroids with one dose of intravitreal dexamethasone (400 μg/0.1 mL). The patient improved symptomatically with no improvement in vision, and on the last follow-up at 10 days, his corneal lesions were stable and tectonically the eye appeared stable. AC appears well formed while the rest of the anterior segment details were not clear.
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pmc-6179972-2
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A 44-year-old male presented with reduced vision in the left eye since a few hours. There was a history of trauma to the left eye with a stone a few hours back. At presentation, the vision in the right was 6/6, N6 and the clinical examination was normal. The left eye vision was recorded as hand motions with a central corneal tear, iris proplapse, 1 mm hypopyon, and a total traumatic cataract (Fig. ). A B-scan ultrasound to rule out a shallow retinal detachment which could not be assessed due to corneal opacity causing media haze was performed, and it showed attached retina with moderate intensity echoes (Fig. ). A provisional diagnosis of open globe injury with traumatic endophthalmitis was made, and the patient underwent left eye corneal tear repair, lensectomy, vitrectomy, and intraocular antibiotic injection. The vitreous sample however was kept at room temperature in the operating room overnight before being sent to the microbiology laboratory for processing. Gram stain of the vitreous biopsy showed long, thick gram-negative filamentous bacilli (Fig. ) giving an impression of actinomycete. However, in culture Klebsiella oxytoca was grown. The organism was sensitive to all antibiotics tested except ampicillin (Table ). Over the next 1 week, the patient underwent a repeat intraocular antibiotic injection (ceftazidime and vancomycin) and an endoscopic vitrectomy due to the presence of significant retinal exudates possibly due to persistent infection not responding to treatment. At the last visit, 10 days post presentation, the vision was PL PR inaccurate with a repaired corneal tear and aphakia. The retina was attached on B-scan.
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pmc-6179972-3
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A 71-year-old diabetic and hypertensive male presented with decreased vision in the left eye since 2 days. The patient underwent a cataract surgery 15 days back elsewhere. On examination, the vision recorded in the right eye was 6/6 N6 and left eye was hand motions close to face. The left eye showed corneal edema, hypopyon, and circumcorneal congestion. A B-scan ultrasound showed moderate intensity echoes in the vitreous cavity with attached retina (Fig. ). A provisional diagnosis of post surgical endophthalmitis was made in the left eye, and the patient underwent a pars plana vitrectomy with intraocular antibiotic injections. The samples were sent to the microbiology laboratory the next day, and Gram and Giemsa stain of the vitreous biopsy then showed slender filamentous bacilli (B) resembling actinomycetes but were non-acid fast. Two days later, the culture showed presence of gray moist colonies, which was identified as Morganella morganii. The organism was resistant to tobramycin, tigecycline, chloramphenicol, ceftazidime, ciprofloxacin, moxifloxacin, imipenum, and colistin and was susceptible to amikacin, meropenum, piperacillin/tazobactum, and gentamicin (Table ). Over the next 3 days, the patient underwent multiple intraocular antibiotic injections of vancomycin and ceftazidime. At the last visit, the vision recorded in the left eye was hand motions close to face with an attached retina on B-scan and reducing echoes.
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pmc-6180351-1
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On March 7, 2013, a 32-year-old woman diagnosed with rhabdomyolysis-complicated ARF was admitted to the Department of Emergency, the First Affiliated Hospital, Sun Yat-sen University with complaints of fever, loss of appetite, general fatigue, and sudden muscle weakness. Fifteen days earlier, she presented to a local hospital with fever, chills, abdominal pain, nausea, vomiting, diarrhea, general fatigue, and sudden muscle weakness without other symptoms or signs. Examination revealed fever, acute kidney injury, hepatic lesion, coagulopathy, and severe anemia. After the preliminary assessment, it was found that rhabdomyolysis was caused by an infectious disease and complicated with multiple organ failure and with possible sepsis. She was rehydrated, transfused and covered with wide-spectrum antibiotics (meropenem), but these treatments did not show any marked improvement.
She was immediately transferred to our emergency department for further evaluation and treatment. Upon arrival, physical examination confirmed the presence of muscle weakness, with muscle strength grade of 2 to 3. Laboratory abnormalities were identified including markedly elevated CK levels that peaked at 8024 IU/L, a Cr level of 37.5 mg/dL, an elevated liver level of the enzyme alanine aminotransferase of 104 U/L, a mild elevated glutamic-oxaloacetic transaminase level of 39 U/L, as well as an activated partial thromboplastin time of 39.2 s, a decreased fibrinogen level of 0.67 g/L, and pancytopenia. Furthermore, chest X-ray examination revealed left lower pneumonia, while abdominal ultrasound examination revealed hepatosplenomegaly. In addition, ultrasound revealed enlargement of retroperitoneal lymph nodes.
As a result, ARF caused by rhabdomyolysis was diagnosed, and treatment was initiated with hydration, continuous hemodiafiltration, and urine alkalization, resulting in significant improvements in physical strength and renal function (Cr=19.5 mg/dL) and decreased CK levels that peaked at 136 IU/L. However, the cause of rhabdomyolysis remained unclear. Recurrent fever and hemophagocytic syndrome were noted. Serum ferritin level elevated dramatically to 40,000.00 ng/mL. Multiple laboratory studies were ordered. Bone marrow aspirate and biopsy were performed on hospital days 5 and 7 to rule out the infiltrative process. Methylprednisolone pulse therapy resulted in moderate improvement of the patient’s general condition.
On admission, the patient was covered with broad-spectrum antibiotics. Her renal and hematological system functions continued to deteriorate, which required hemodialysis and multiple transfusions. Pancytopenia worsened. She progressed to multi-organ failure and needed bi-level airway pressure ventilation. On hospital day 9, the patient was discharged due to treatment abandonment. Six hours after discharge from the hospital, she expired at home without a definitive premortem diagnosis. The results of the examinations of the bone marrow aspirate and biopsy are shown in –
.
Hematopoietic tissues in the bone marrow contained a scattered mass of specific cells with a patchy distribution. These cells sized from small to medium, the nuclei were pale, enlarged and irregular, including a thin karyotheca, inconspicuous nucleoli, a partly visible nucleoli, and interstitial fibrous tissue hyperplasia.
Atypical cells CD2, CD3, CD5, CD7, and TIA1 were found positive, CD20, CD79a, and CD117 were found negative, and MPO myeloid cells were positive.
Lesions conformed to the abnormal proliferation of bone marrow T lymphocytes. The diagnosis was considered to be T-cell lymphoma involving the bone marrow.
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pmc-6180387-1
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Patient 1 is a 75-year old male, who was originally diagnosed with stage IIIB, BRAF-negative melanoma of the upper back and left axillary lymph node (LN) involvement in 2012, treated with wide local excision (Breslow thickness: 2.9 mm) and axillary LN dissection. The patient received adjuvant therapy with a GM-CSF secreting allogeneic melanoma cell vaccine for 3-years, but developed recurrent disease at the right buttock, inguinal nodes and lung in 2015, and was treated with first-line pembrolizumab monotherapy. He received 25 total doses and sustained a radiologic complete response to therapy by RECIST 1.1 v.5.0. After 20 doses of pembrolizumab therapy, he developed acute back pain; a contrast-enhanced MRI of the full spine demonstrated multiple, non-traumatic vertebral compression fractures, rib fractures, and as well as pelvic fractures sustained during therapy, without bone metastases. ICI therapy was continued, however he developed additional compression fractures and more profound vertebral wedging (Fig. ), prompting discontinuation of pembrolizumab after 18-months of therapy. The patient’s biochemical workup was unremarkable. His degree of active bone resorption, as measured by C-telopeptide levels (CTX, Table ) were elevated despite three-weeks of alendronate use prior to appointment. Bone density at the hip (lumbar spine excluded in the setting of fracture) demonstrated osteopenia only. Histomorphometry from transiliac bone biopsy (Fig. ) revealed bone resorption (increased eroded surface, osteoclast surface) and bone loss (reduced trabecular and cortical parameters). Given the patient’s continued bone loss on oral bisphosphonate, he received one infusion of intravenous bisphosphonate (zoledronic acid), underwent multiple kyphoplasty procedures, and permanently discontinued pembrolizumab. At present, his melanoma continues to be in complete remission 35-months after commencement of pembrolizumab, and after therapy has been held for 20-months. The patient continues to receive IV bisphosphonate yearly in the form of zoledronic acid.
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pmc-6180387-2
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Patient 2 is a 52-year old male who was originally diagnosed in 2011 with a localized BRAF V600E- melanoma of the left flank, and was treated with wide local excision (Breslow thickness: 2.8 mm) and adjuvant interferon alpha. Unfortunately he developed recurrent disease in 2014 with new lung metastases, and was treated with high-dose interleukin-2 (IL-2). His disease progressed through this therapy, with the development of new osseous metastases in the axial and appendicular skeleton. He was subsequently treated with nivolumab in combination with IL-21 on a prospective clinical trial for 8 cycles of combination therapy, followed by nivolumab monotherapy. He went on to have a near complete response to ICI therapy by RECIST 1.1, with his known osseous metastases in the ribs, pelvis, femur, humerus and vertebral bodies L3 / L4 showing sclerotic change consistent with treatment response. No skeletal radiation was administered. Given his near complete response, ICI therapy was discontinued. Seven months following the cessation of therapy, the patient developed new brain metastases, pulmonary metastases, and a paraspinal metastasis at S3. The patient was treated with stereotactic radiosurgery (SRS) of the paraspinal mass and brain and was initiated on second-line dabrafenib and trametinib. After 8-months, there was an interval increase in size of the S3 paraspinal mass, and nivolumab was re-challenged. The patient went on to receive 9-months of additional ICI therapy at which time the first vertebral fracture – not associated with a metastatic lesion – was detected. The patient’s cancer was deemed to be stable is at all known sites of disease at that time. Specifically, on surveillance CT imaging, compression deformities of T2–5 were identified with new compression fractures noted at T6–12 and L1 at the time of clinic visit and vertebral fracture assessment. There was only one sclerotic lesion in the thoracic spine (T7) identified as a metastatic focus of disease; the remaining compression fractures developed in the absence of skeletal metastases. The patient’s biochemical evaluation was unremarkable. Bone density testing showed only osteopenia at the femoral neck. For treatment, he received denosumab injections every 6-months. At that time, he commenced third-line ipilimumab /nivolumab combination therapy. While the patient did not suffer additional fractures, his melanoma progressed, and he passed away 7-years after initial diagnosis.
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pmc-6180387-3
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Patient 3 is a 58-year old male diagnosed with stage IV, BRAF-negative melanoma of the left ear in 2014 (stage 0) with progression to metastatic disease of the lung in 2016. The patient received first-line therapy with single agent pembrolizumab for 10-months with excellent response at which time a restaging CT indicated abnormalities of the thoracic and lumbar vertebral bodies. He carried no prior history of fracture, and no spinal metastases were identified. A comprehensive review of his outside imaging revealed an age-indeterminate T12 compression fracture sustained prior to ICI with an adjacent T11 compression deformity appearing after approximately 10 months of pembrolizumab therapy. Increased prominence of biconcave deformities of the vertebral bodies were also noted during therapy, indicating osteopenia (Fig. ) []. Given the patient’s response to therapy, pembrolizumab was discontinued after 12-months, though he was referred to the Metabolic Bone Center for continued skeletal evaluation and management. At the time of evaluation, his laboratory testing showed calcium and vitamin D deficiency. Markers of bone formation and resorption were considered normal for the patient’s sex and age and not suggestive of a high bone loss state. Bone density testing revealed only low bone density at the hip, but no frank osteoporosis. Following optimization of calcium and vitamin D status through diet and supplement, the patient retuned to clinic with updated laboratory testing. His biochemical profile indicated improved calcium and vitamin D indices as well as stable markers of bone formation and resorption. Repeat bone density testing also revealed no significant change of bone density in the hip or spine. Extensive discussion was had with the patient involving the risks and benefits of antiresorptive medications (oral / parenteral bisphosphonate vs. denosumab) in patients with vertebral fracture. He has elected to defer management beyond calcium, vitamin D and lifestyle optimization given that he is no longer taking pembrolizumab and his skeletal condition has been stable 1-year after ICI cessation. He will return to the metabolic bone center yearly for ongoing surveillance with biochemical testing and DXA imaging. In the event of ongoing bone loss or new fracture, we will revisit initiation of antiresorptive therapy. Oncologically, the patient has stable disease and has experienced neither a complete response nor progressive disease (non-CR, non-PD).
Three patients had new destructive or resorptive appearing bony lesions that were not consistent with metastases. Two patients [, ] had their lesion discovered due to pain and/or swelling in the affected area prompting subsequent imaging, while patient 6 had the lesions discovered incidentally on PET scan. All three patients had concomitant inflammatory arthritis affecting separate joints with signs of systemic inflammation. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies, and anti-nuclear antibodies were negative in patients 4 and 5; patient 6 did not have autoantibody testing. All patients had increased bone resorption markers (CTX, Table ).
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pmc-6180387-4
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Patient 4 is a 59-year old male diagnosed with stage IV melanoma involving the liver only. He was treated with the first-line ipilimumab and nivolumab combination and experienced two irAEs (hypophysitis after 2-months of ICI,pneumonitis after 3-months of ICI therapy, with a second pneumonitis episode 5-months after ICI start). Eight months after ICI start, the patient developed progressive symptoms of shoulder discomfort and impaired mobility. Imaging showed a destructive lesion with surrounding bone marrow edema affecting the humeral head and the glenoid (Fig. ). He had extensive evaluation of his destructive shoulder lesion for potential infection or metastasis. Two separate bone biopsies showed only a mixed inflammatory infiltrate; he was started on a corticosteroid taper by his oncologist. Upon evaluation by rheumatology, his inflammatory markers were elevated; he had synovitis in the small joints of the hands and wrist, consistent with inflammatory arthritis. Based on his inflammatory arthritis, bone biopsies showing sterile inflammation and elevated inflammatory markers, he was started on therapy with adalimumab, a TNF-inhibitor. No new bony lesions developed after discontinuation of immunotherapy, and his arthritis and shoulder pain improved with adalimumab therapy. His melanoma remains in remission after 16 months of TNF-inhibitor therapy.
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pmc-6180387-5
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Patient 5 is a 60-year old female who was diagnosed with stage IV clear-cell renal cell carcinoma with metastases to the lungs, brain, and bones (vertebrae, forearm). The patient was treated with first-line nivolumab and received whole brain radiation therapy, with stable disease by RECIST 1.1 after 6 doses of therapy. After 18 months of nivolumab therapy, she developed new onset right wrist swelling and stiffness. Symptoms of pain and stiffness were not severe, but a radiograph of the right wrist and hand showed resorption of two entire carpal bones and changes typical of inflammatory arthritis, namely periarticular osteopenia of metacarpophalangeal and proximal interphalangeal joints (Fig. ). She was briefly started on a clinical trial of nivolumab and an anti-LAG3 agent, but this was discontinued due to disease progression. Her first evaluation at our center was after starting this clinical trial. At that point, she was found to have inflammatory arthritis involving the knees, metacarpophalangeal and proximal interphalangeal joints. Per the patient’s recall, the inflammatory arthritis symptoms in joints other than the wrists started 2-months after the initial wrist swelling. Prednisone 10 mg daily was started with improvement in joint swelling, but the patient developed worsening brain metastases and entered hospice care. Further evaluation and management were not pursued in light of her progressive disease and the decision was made to transition to palliative care.
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pmc-6180440-1
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A 15-year-old Indian Hindu boy from a low socioeconomic stratum presented to Surgical emergency with complaints of difficulty in passing stools for 1 month, passage of blood and mucus per rectum for 15 days, abdominal distension for 1 week, and obstipation for 3 days. These symptoms were associated with significant appetite and weight loss but there was no history of fever, jaundice, melena, hematemesis, hemoptysis, cough, chest pain, or shortness of breath. There was no history of similar illness or other malignancy in his family. He was not on any medication.
On examination he was conscious and oriented. He had a thin build and pallor. He was afebrile. His pulse rate was 84/minute and blood pressure (BP) was 110/74 mmHg. His abdomen was distended with no local bulge. On digital rectal examination, a circumferential proliferative growth was felt 1 cm above the anal verge, which was almost completely occluding the lumen. On scrotal examination, a small nodule was felt in his right testis. The rest of the systemic examination was normal.
An abdominal and chest X-ray was done as preliminary investigation which revealed signs of intestinal obstruction (Fig. ).
In view of intestinal obstruction, he was taken into our emergency operation theater and a diverting loop sigmoid colostomy was performed. His symptoms were relieved, and stoma was well functioning and healthy.
A punch biopsy was taken from anorectal growth. The histopathological examination (HPE) report suggested signet ring cell adenocarcinoma of rectum (Fig. ). Tumor markers report showed: carcinoembryonic antigen (CEA) 499.93, alpha-fetoprotein (AFP) 2.42, beta human chorionic gonadotropin (HCG) < 1.2, and lactate dehydrogenase (LDH) 593.
Routine investigations including complete blood count (CBC), and liver and renal function tests were within normal limits. His urine analysis was also normal.
Contrast-enhanced computed tomography (CECT) of his chest, abdomen, pelvis, and brain was done as a part of metastatic workup which showed diffuse circumferential homogenous thickening involving rectum approximately 1 cm from the anal verge and extending into sigmoid colon proximally up to colostomy site. Multiple enlarged lymph nodes, some showing necrosis, were noted in perirectal, iliac, bilateral para-aortic, periportal, and celiac regions. Moreover, multiple enlarged lymph nodes were seen in the mediastinum in bilateral paratracheal, prevascular, and subcarinal regions, and in left supraclavicular region. In addition, hepatomegaly with liver measuring 17.8 cm was present. However, no lesion was seen in liver parenchyma. There was mild left-sided pleural effusion (Figs. and ). There was no lesion in his brain suggestive of metastasis. His right testis was enlarged. Ultrasonography (USG) showed a hypoechoic nodule (Fig. ) in his right testis from which a fine-needle aspiration biopsy was done, which revealed metastatic adenocarcinoma (Fig. ).
In view of distant metastasis, we planned to give our patient neoadjuvant chemotherapy. However, within 2 weeks of surgery he developed progressive respiratory distress. A chest X-ray showed infiltrations and bilateral pleural effusion. He was intubated and was kept in our intensive care unit (ICU). However, his condition deteriorated and he developed multiple organ dysfunction syndrome (MODS) in the next few days. Eventually he died with multiple organ failure. An autopsy was not performed as per the wish of his family members. The entire course of illness from appearance of first symptom to death was only 2 months.
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pmc-6180451-1
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An 11-year-old male was referred for further diagnostics due to developmental delay, intellectual disability and microcephaly. He was the first child born to apparently healthy non-consanguineous parents. The mother had an uneventful pregnancy with no history of prenatal exposure to alcohol, drug or tobacco. Though his siblings (7-year brother and 3 years old sister) were phenotypically normal, his paternal cousin-sister was microcephalic and mentally challenged. No investigations were carried out in the affected cousin-sister.
The proband was born by normal vaginal delivery. The birth weight was 1.5 kg and head circumference was 33 cm. Apgar score at birth was within the normal range. The patient was sitting without support at around 1.5 years. He could stand with support by 2 years and independent walking at 2.5 years. His speech development was delayed. He was not able to speak sentences and could not achieve proper bowel and bladder control even at the time of presentation (11 years). His height and weight were 108 cm and 14.5 kg respectively (below 10th centile); head circumference (OFC; Occipital Frontal Circumference) was 42 cm (below 3rd centile). The proband portrayed short stature and microcephaly with developmental delay. The facial dysmorphism showed long face, small chin, large protruding ears, slightly upturned eyes, sparse eyebrows, large bulbous nose and thin upper lip (Fig. and ). Speech delay, penile chordee and sacral dimple were also noted during physical examination. His respiratory, cardiovascular and abdominal examinations were unremarkable. CNS examination showed intellectual disability, delayed language development and hyperactivity. His speech and cognitive development was more delayed than his motor milestones, and academic performance was very poor. His serum TSH (thyroid stimulating hormone) and GH (growth hormone) levels were normal. Magnetic resonance imaging (MRI; performed at an age of 10 years) showed demyelination in both frontal and parietal lobes (Fig. ). Ultrasonography of abdomen and pelvis were normal, as were echocardiogram and ophthalmologic examinations.
Sample collection and written informed consent was obtained according to the need of the institutional ethics committee in accordance with Helsinki declaration. Chromosome analysis of the patient was performed with 72 h lymphocyte culture and standard GTG-banding. The karyotype was interpreted according to the International System for Human Cytogenetic Nomenclature (ISCN 2016) [] as mos 46,XY,r(6)(p25.3q27)[54]/45,XY,-6[13]/46,XY,r(6)(::p25.3→q27::p25.3→q27::)[13]/46,XY[6]/47,XY,r(6)(p25.3q27)×2[2]dn (Fig. ).
Karyotype of the parents was normal, confirming a ‘de novo’ origin of the r(6). Further analysis was carried out by molecular karyotyping using Affymetrix CytoScan™ 750 K array. Data was analyzed using Chromosome Analysis Suite (ChAS) and revealed: arr [GRCh37] 6pterp25.3(156,974_665,234)x1,6p25.3(668,700_1,929,528)x3,6q27qter(170,466,513_170,914,297)×1. In other words, there was a partial terminal monosomy of overall 508 kb in 6p25.3 followed by a 1.3 Mb contiguous duplication in 6p25.3 and 448 kb terminal deletion in 6q27 (Fig. ). These results were confirmed by fluorescence in situ hybridization (FISH) using commercially available subtelomeric probes for 6pter and 6qter. The duplicated region in 6p25.3 could not be confirmed by another method due to lack of corresponding locus-specific probes. The dicentric nature of double ring was thus established by a centromeric probe (Fig. ).
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pmc-6180468-1
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A 62-year-old female, with primary bone marrow aplasia was admitted in the intensive
care unit (ICU) with septic shock, hematomas and petechiae spread throughout the
body. A physical examination revealed impaired conscious level, tachycardia, and
hypotension. Laboratory examination revealed the following: hemoglobin 8.2g/dL,
leukocytes 290/mm3, platelets 1000/mm3, fibrinogen 1050mg/dL,
international normalized ratio 1.1, C-reactive protein 52mg/dL, and creatinine
1.1mg/dL (). Orotracheal intubation
was performed due to respiratory insufficiency and an impaired conscious level.
Norepinephrine and antibiotics were started. A computed tomography was performed
showing bilateral alveolar infiltrate. Bronchoscopy and bronchoalveolar lavage were
requested to investigate the etiological cause. Due to severe thrombocytopenia,
thromboelastometry was requested to determine whether the bronchoscopy could be
performed safely. EXTEM (Extrinsic rotational thromboelastometry) showed MCF of 50
millimeters (mm), ML (Maximum Lysis) of 0%, and FIBTEM (Fibrinogen rotational
thromboelastomery) showed MCF of 40mm (
and ). The patient presented with a
normal coagulable profile according to thromboelastometry even with extremely low
platelet quantitative levels (1000/mm3). Bronchoscopy was safely
performed with signs of bilateral alveolar hemorrhage, with the presence of
organized clots in the inferior lobe segment but without active bleeding. The
patient was extubated seven days after bronchoscopy, without any signs of bleeding.
Laboratory test results showed an increase in platelet counts as well as a reduction
in fibrinogen concentration with the improvement of sepsis (). She was discharged from the ICU three days after
extubation.
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pmc-6180503-1
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A 43-year-old Chinese woman was diagnosed with SLE 5 years ago, and has been receiving ongoing treatment with prednisone and omeprazole orally. Starting from 2 years ago, the patient had difficult defecation and watery stools with left lower abdominal pain, usually half an hour postprandially. The symptoms had become progressively worse over the previous 2 months, and the patient was referred to our hospital.
Her physical examination on admission was normal except for a palpable lower abdominal mass, about four cube centimeters. Laboratory data displayed a high level of globulin, elevated D-Dimer level and weakly positive fecal occult blood test (Table ). The serum levels of tumor biomarkers of colon cancer, carcinoembryonic antigen and CA19–9, were normal (Table ).
Upper abdominal computed tomography (CT) scan showed that wall thickening partly occurred in the ascending colon, indicating a tumor lesion (Fig. ). Lower abdominal enhanced CT scan revealed wall thickening in the proximal ascending colon, distal cecum and ileum, which suggests a tumor lesion and peri-intestinal infiltration (Fig. ). A colonoscopy displayed a space-occupying lesion in the ascending colon (Fig. ).
Based on the evaluation mentioned above, colon cancer with SLE was suspected pending the biopsy results. A radical bowel resection was considered as a preferred strategy. However, the patient had taken prednisone and omeprazole per os for an extended time period, which increases the susceptibility to possible complications, such as infection, gastrointestinal bleeding or perforation, hyperglycaemia, hyperlipemia, osteoporosis and iatrogenic hyperadrenocorticism. Thus, in order to avoid adrenal insufficiency symptoms, the patient was administered methylprednisolone instead of prednisone during surgery (0.8 mg/kg/day, including the day before and after surgery).
During the laparoscopic surgery, a huge and hard space-occupying lesion was observed around the wall of the cecum, extending into the serosa and retroperitoneum (Fig. ). The liver, stomach, duodenum and pelvic cavity appeared normal, and the pelvic cavity was negative for peritoneal fluid accumulation. A drainage tube was placed at anastomotic site without preventive colostomy because the tissues of patient were good in elasticity and the blood supply of ileum and transverse colon was normal.
The biopsy report indicated a moderately differentiated adenocarcinoma with mucinous differentiation (size: 7 × 4.5 × 2.2 cm3; Fig. &b). The metastasis was only detected in the adjacent lymph node of the tumor (1/17). The tumor was classified as T3N1M0 (stage III).
The patient was subsequently treated by mFOLFOX6 chemotherapy (oxaliplatin/5-fu/leucovorin). The postoperative level of plasma glucose was carefully monitored. The patient was also treated with proton pump inhibitors post-surgery to prevent the development of stress ulcers. Postoperative calcium supplementation was also offered. Another postoperative consideration was that lipid emulsion was not used. The patient recovered well after the surgery and the chemotherapy (Tables and ).
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pmc-6180520-1
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In March 2016, a 71-year-old female of Caucasian origin was referred to Amiens-Picardie University Medical Center (Amiens, France) for gait impairment. Magnetic resonance imaging (MRI) showed a voluminous mass in the right temporal lobe, the features of which were strongly suggestive of GBM. The patient underwent subtotal resection. A histopathologic study of FFPE surgical samples submitted in toto revealed a dense proliferation of highly atypical tumor cells. Many atypical mitotic figures were observed. Angiogenesis had produced large glomeruloid vascular channels. These morphological features were highly subjective of GBM. The tumor cells were labelled by antibodies against GFAP and Olig2 but not by an antibody against isocitrate dehydrogenase 1 (IDH1)-R132H. A diagnosis of IDH-WT glioblastoma was made, and the MGMT promoter was found to be unmethylated. Following our observation of an EGFR mutation, a complementary immunohistochemical study was performed in order to rule out a diagnosis of bronchopulmonary carcinoma: the tumor cells did not expresss polyclonal AE1/AE3 cytokeratin, CK7, NapsinA, TTF1 or P40. After the patient has provided her written, informed consent, she was enrolled in the Bi-GlAM study (designed to evaluate plasma DNA in GBM patients during their clinical follow-up).
The panel-based NGS mutational profile revealed several SNPs and one somatic mutation (Table ). The tumour did not present any IDH 1 (exon 4) or IDH 2 (exon 4) mutations, prompting a histomolecular diagnosis of IDH-WT glioblastoma. The c.2582 T > A substitution in the EGFR gene was of particular interest; it resulted in an amino acid change at position 861 from leucine (Leu, L) to glutamine (Gln, Q). Hence, a p.L861Q mutation (COSM6213) was unambiguously identified. The allele frequency was 17% (T = 0.8308 and A = 0.1692; Table ). However, this ratio was not consistent with the tissue’s tumor cell content, as evaluated by the pathologist (around 80%). When comparing the results for samples from the same run, we found that the number of reads for each EGFR exon was much higher in the patient’s tumour (Additional file : Table S2; by around 10-fold for exons 12 and 21, and 15-fold for exons 18, 19 and 20). This finding strongly suggested the occurrence of EGFR gene amplification, which was later confirmed by the aCGH experiments.
As shown in Fig. , the tumor presented a loss of chromosome 10 (mean log ratio: − 0.446) and a partial loss of the short arm of chromosome 9 (9p24.1-p21.2, mean log ratio: − 0.385) including the homozygous deletion of CDKN2A gene (arrow, mean log ratio: − 1.155) and a gain in chromosome 7 (mean log ratio: 0.376) including the amplification of EGFR gene (arrow, mean log ratio: 3.642). The combination of tri/polysomy of chromosome 7 and loss of heterozygosity of 10q are characteristic molecular features in GBM - especially when they are associated with EGFR amplification []. Additional chromosomal aberrations could be observed, such as gain of chromosome 2 (mean log ratio: 0,367), gain of chromosome X (mean log ratio: 0.398), amplification of the MDM4 gene (1q32.1, mean log ratio: 3.681) and loss of the short arm of chromosome 14 (mean log ratio: − 0.416).
The NGS and aCGH data all confirmed the EGFR gene amplification, and suggested that the p.L861Q mutation was not present in all EGFR alleles (since the observed allele ratio was only 17% for the mutation).
The presence of this unusual mutation in a case of GBM was confirmed by ddPCR using a TaqMan assay to discriminate between the WT and p.L861Q alleles. As shown in Fig. , the mutation was detected in the FFPE DNA sample from the primary tumour with an allele frequency of 18% (8433 out of 46,948 droplets).
The first-line treatment comprised subtotal resection of the lesion (in March 2016), a combination of radiotherapy and TMZ, and then adjuvant TMZ []. After four cycles of TMZ, however, disease progression (according to the Revised Assessment in Neuro-Oncology criteria, RANO []) was observed on MRI (Fig. ). Given the presence of the p.L861Q EGFR mutation (known to confer sensitivity to second generation TKIs [–]), the patient started a second-line course of off-label treatment with afatinib after the provision of fully informed consent. A radiological disease assessment after 1 month of afatinib treatment (40 mg/day) did not reveal any significant lesion growth (i.e. stable disease; Fig. ). The occurrence of asthenia prompted us to reduce the dose of afatinib to 30 mg/day. A month later, MRI revealed an increase in contrast enhancement (i.e. disease progression; Fig. ). We withdrew the TKI at this point, and initiated third-line treatment with bevacizumab and lomustine. The patient died in July, 2017.
In an attempt to monitor the tumour response and to detect recurrent disease during clinical surveillance, a specific ddPCR assay was used to assay circulating DNA from plasma samples for the L861Q-mutation. The plasma samples were collected before concomitant radiotherapy/TMZ, 1 month after radiotherapy, 1 month after the first cycle of TMZ, 1 month after the fourth cycle of TMZ, after 9 weeks of afatinib treatment, and after two cycles of lomustine with bevacizumab, and assayed for the presence of the p.L861Q mutation. The plasma DNA concentration for each sample is indicated in Fig. . However, the p.L861Q mutation was not detected at any of the monitoring time points.
Given that (i) EGFR alterations are the most frequent genomic defects in GBM, and (ii) a number of targeted therapies are on the market, we performed short-term cultures of neurosurgical tumour resections with the EGFR-targeting drugs cetuximab, erlotinib and afatinib. Each drug’s effect was evaluated as the percentage of Ki67-positive tumour cells in an immunochemical assay and a visual assessment. There were no statistically significant differences between the negative control on one hand and cetuximab (p = 0.45), afatinib (p = 0.6) and erlotinib (p = 0.37) on the other (Fig. and ) - suggesting that all three molecules would have been poorly active against the patient’s tumour.
We also used immunoblotting to assess expression levels of the markers ERK and phospho-ERK (pERK) in samples obtained by short-term culture. The pERK/ERK ratio (reflecting the activation of the RAF-MEK-ERK pathway) was calculated by densitometric analysis of the immunoblot (Fig. and ). When compared with a negative control, neither cetuximab, afatinib nor erlotinib was associated with a statistically significant difference in the pERK/ERK ratio (p = 0.36, 0.99 and 0.59, respectively).
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pmc-6180582-1
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A 24-year-old woman with a 6-month history of swelling in the left floor of her mouth was referred to our institution. Although she experienced slight difficulty in swallowing, she did not experience pain or tongue paralysis. Her medical and family histories were unremarkable.
Intraoral examination revealed a well-defined 3.5 × 3 × 2 cm-sized solid, spherical submucosal nodule adjacent to the sublingual gland; the nodule was covered with light bluish smooth mucus (Fig. ). The patient experienced slight pain when pressure was applied to the tumor. Mobility and sensory functions of the tongue were normal, and no lymphadenopathy in the submandibular region was detected on palpation. All relevant laboratory test results were normal. Enhanced computed tomography revealed a 2.8 × 1.8 × 2.1 cm-sized well-defined, solid, heterogeneous nodule that did not appear to involve the mandible (Fig. ). In addition, a three-dimensionally reconstructed image showed a nodular lesion occupying the left floor of the mouth with abundant blood flow (Fig. ). No enlarged lymph nodes were found in the submental or submandibular regions.
The initial clinical impression was a benign salivary gland tumor, dermoid cyst, or benign connective tissue neoplasm. The patient was scheduled for surgery via an intraoral approach. First, an elliptical incision was made around the periphery of the sublingual gland through only the oral mucosa, and a full-thickness tissue flap was prepared along the lingual aspect of the sublingual gland. After the sublingual gland was freed from its surrounding tissue with blunt dissection, a well-circumscribed tumor without capsular extension was found beneath the body of the sublingual gland and located above the submandibular gland duct and lingual nerve. The submandibular gland duct and lingual nerve were carefully freed from the tumor surface, and the complete tumor was excised along with the sublingual gland (Fig. ). The tissue sample was fixed with 10% formalin and submitted for histopathological diagnosis.
Microscopically, the tumor cells were round, oval, polyhedral, or fusiform and were arranged in organoid and sheet-like patterns with vascular lumens. Most of their nuclei were small and round within an amphiphilic or slightly eosinophilic cytoplasm. Nuclear atypia was rare (Fig. ).
Immunohistochemistry revealed that the tumor cells yield positive results for vimentin and alpha-smooth muscle actin, but negative results for desmin, anti-cytokeratin (AE)1 or AE3, cluster of differentiation (CD)31 and CD34, and S-100, and exhibited a Ki-67 index of 5%. These findings were consistent with those for a glomus tumor.
After surgery, the patient had an uneventful recovery with primary healing and had no evidence of recurrence over 4 years of follow-up.
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pmc-6180591-1
|
Case 1 is a 19 years old woman (for timeline see Fig. ). She was born at 37 weeks gestation with a birth weight of 2890 g, length 47 cm, and a head circumference of 32 cm. Pre- and neonatal periods were normal. She had her first seizure, a prolonged febrile seizure, at 5 months of age. She developed afebrile focal seizures and intractable generalized seizures, both myotonic, tonic and tonic-clonic. She has had several episodes with convulsive status epilepticus. Her early development, however, was unremarkable. She developed normal hand function, including a pincer grip, and started to use a few words, 15 at the most. She began walking independently at 17 months. However, from around 15 months of age her development slowed down and she gradually lost acquired skills. She stopped using her hands, her words disappeared and her gait became broad-based and ataxic. She developed midline rubbing hand stereotypies, although not very intense, and bruxism. She often had breath-holding spells and infrequently she hyperventilated. Her sleep pattern was impaired with night time screaming spells and occasionally laughing spells. Between one and 2 years of age, she developed autistic traits. She had a deceleration of head growth from 50th to 10th percentile.
The clinical examination at 19 years revealed a woman with intense eye contact and ongoing stereotypic hand movements with hand dyspraxia. She had a broad-based gait with notable ataxia. Breath holding and teeth grinding were observed. She was only 141 cm tall, but had normal weight for height. Her musculature was generally hypotonic and she had a slight scoliosis. Her epilepsy was still aggressive with daily seizures (focal, tonic and tonic-clonic), despite intense anti-epileptic treatment. Her clinical signs and symptoms were consistent with classic RTT, fulfilling the criteria of this disorder.
CT and MRI scans of the brain were unremarkable. At the age of eleven MECP2, CDKL5, and FOXG1 were analyzed with Sanger sequencing of all exons with flanking intron regions and MLPA kits P015C, P395 and P189 from MRC-Holland, all with normal results. Due to the aggressive epilepsy SCN1A was Sanger sequenced and this disclosed the novel splice variant NG_011906.1:g.76169G > C, (NM_001165963.2): c.4284 + 1G > C. Using Alamut Visual software (Interactive Biosoftware, France) and the guidelines of American College of Medical Genetics and Genomics and the association for Molecular Pathology (ACMG) [], this variant was scored as pathogenic. Parental testing indicated that the mutation was de novo. Two splice mutations (c.4284 + 1G > T and c.4284 + 1G > A) affecting the same splice site, have previously been reported in Dravet syndrome [, ]. Because she fulfilled the criteria for RTT, but no mutation in MECP2 was identified, a MECP2 gene expression analysis, performed on mRNA isolated from her fibroblasts was performed. This analysis indicated that her MECP2 expression level was more than 80% reduced compared to three female controls (Fig. ).
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pmc-6180591-2
|
Case 2 is a 32 years old woman (for timeline see Fig. ). She was born at 40 weeks of gestation with a birth weight of 3830 g, length 52 cm, and a head circumference of 36 cm. Pre- and neonatal periods were normal. At 7 months, she had her first seizure, a febrile bilateral tonic-clonic seizure. Between one and 2 years of age her epilepsy became more severe, with daily generalized seizures. The frequency of seizures declined somewhat when she reached school age, but her epilepsy remained drug resistant, with several bilateral tonic-clonic seizures every week. Besides the epilepsy, her development was apparently normal the first 12–15 months. She sat independently at 7 months. At 1 year, she used a few words and had an appropriate use of hands. She learned to walk when she was 24 months old. When she was between 12 to 15 months of age she started to lose acquired skills. Her hand function deteriorated gradually, her words disappeared and she no longer seemed to show interest in her surroundings. She developed bruxism and hand-washing stereotypies. She could walk independently until school age, but then she gradually needed support when walking. Through childhood her sleep pattern was significantly disturbed with both screaming and laughing spells. Her respiration has however never been affected.
The clinical examination revealed a 32 years old woman who could walk a few meters with support, had ataxic and apraxic hand movements, but not hand stereotypies. She had no language but gave intense eye contact. Her muscle tone was normal. She had a slight scoliosis. Her epilepsy was still a major concern, with daily to weekly bilateral tonic-clonic seizures. She fulfilled the criteria of classic RTT.
Genetic analyses of MECP2 at the age of 18 gave negative results (Sanger sequencing and MLPA kit P015 from MRC-Holland). As a participant in a national survey of females with RTT she was recently retested by applying whole exome sequencing (WES) using Agilent SureSelect Target Enrichment Kit (Agilent Technologies, Santa Clara, CA) on Illumina HiSeq 2500 with pair-end runs. Alignment, mapping, and variant calling were performed using Genome Analysis Tool Kit (GATK). Reads were mapped to the reference sequence (GRCh37/hg19). Following bioinformatic filtration, analysis of coding regions and intron/exon boundaries of 1479 predefined genes (including FOXG1, CDKL5 and SCN1A with a 100% coverage at a depth > 10×) was performed. WES disclosed the variant, NG_011906.1:g.76130G > T, NM_001165963.1: c.4246 G > T, p.(Asp1416Tyr) in SCN1A. Using Alamut Visual software (Interactive Biosoftware, France) and ACMG criteria [] this novel variant was scored as pathogenic. Parental testing indicated that the mutation was de novo. This is a novel variant, but mutations affecting the same amino acid have been reported in Dravet syndrome [].
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pmc-6180599-1
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A 7-month-old female presented with acute pneumonia, diarrhea, failure to thrive and candidiasis. The patient had no evidence of neurological disease. Immunologic investigation identified absolute lymphopenia with low CDs and Immunoglobulins. A diagnosis of T-B− SCID due to RAG2 homozygous mutation [c.283G>A] was confirmed. An iVDPV2 was detected and viral shedding persisted for 5 months until death from pneumonia.
A 6-month-old female infant presented with recurrent oral thrush and unresolving pneumonia. Her family history was positive. Screening identified lymphopenia with low CDs and Immunoglobulins. A diagnosis of T-B− SCID was made, and the molecular defect was found in the DCLRE1C gene. She had received 3 doses of OPV. An iVDVP2 with 11 nucleotide differences from Sabin vaccine strain was detected and viral shedding persisted for 3 months until death after a failed BMT.
A 10-month-old male born to consanguineous parents presented with unresolving pneumonia, pericardial effusion, draining ears and persistent candidiasis. Screening identified leucopenia, lymphopenia, low CD3 and CD4 levels, and undetectable immunoglobulins. A diagnosis of MHC class II deficiency was made with a homozygous mutation in RFX5 [c.715C>T]. Shortly after diagnosis, he developed AFP and iVDPV2 with 11 nucleotide differences from Sabin vaccine virus was detected and viral shedding persisted for 3 months until the patient died. The patient received 5 doses of OPV, including 3 doses of trivalent OPV and 2 doses of bivalent OPV (containing serotypes 1 and 3).
A 6-month-old male infant presented with AFP following the second dose of OPV. Illness started as loss of neck support along with asymmetrical weakness involving both lower limbs, followed by generalized weakness and seizures. Acute disseminated encephalomyelitis (ADEM) was suspected and the patient received intravenous immunoglobulin (IVIG) and steroids. On assessment he was leucopenic and lymphopenic; had low CDs. His IgG was high (just received IVIG) and IgM was low. A diagnosis of T-B+ SCID was made, but the molecular defect was not identified. MRI scanning of the brain showed atrophic frontal lobes with bilateral thalamic patches, judged to be mostly inflammatory in nature. Electromyogram was suggestive of anterior horn cell lesion. The infant also showed a picture of viral myocarditis based on echocardiography with elevated troponin I and mass creatine kinase (MMB). Stool sample revealed iVDPV2 excretion with 1% nucleotide divergence (10 nucleotide differences). Patient died after 3 months.
A 14-month-old male presented with AFP associated with disturbed consciousness following OPV. Over 40 days, the patient gradually improved with the left lower limb more affected than the left upper limb, with regain of neck support and ability to sit unsupported. EMG showed evidence of anterior horn cell loss. Following another OPV dose at the age of 9 months, the patient developed progressive right lower limb weakness; both upper limbs were also affected. The clinical condition slightly improved till clinical relapse was reported by the family 15 days after a newborn sibling received OPV. No specimens were collected at that time. On assessment, he had otitis media once. Investigations showed a normal leucocytic count with complete absence of B cells (CD19: 0) and undetectable immunoglobulins. A diagnosis of agammaglobulinemia was made. An iVDPV2 with 17 nucleotide differences from Sabin virus, and SL3 were detected in a stool sample. Viral shedding lasted for 5 months and ceased following IVIG administration.
A 22 month-old female, presented with persistent diarrhea, recurrent pneumonia and repeated blood transfusions. One month after her fourth polio dose at the age of 7 months, she developed fever, convulsions, and disturbed consciousness and was admitted with the diagnosis of meningoencephalitis. Investigations showed a low leucocytic count with absolute lymphopenia (ALC: 1656), low CDs and immunoglobulins. A diagnosis of T-B+ SCID was made. Stool sample revealed IVDPV1 with 22 nucleotide differences. The patient died 2 months later.
A 9-month-old female, presented with persistent diarrhea, pneumonia and failure to thrive. At the age of 11 months she developed right lower limb hypotonia followed left lower limb affection and progressed to bulbar symptoms followed by coma. The patient received IVIG repeatedly without improvement. EMG and nerve conduction results were consistent with severe diffuse axonal polyneuropathic disease. Family history was positive and investigations revealed CD4 lymphopenia, with undetectable immunoglobulins. There was very defective expression of MHCII on the surface of lymphocytes [HLA DR was 0.6% and CD19+/DR+ was 0.3%]. The diagnosis of MHC Class II deficiency was confirmed by identifying a homozygous missense mutation in RFXANK gene [c.431T>C]. The first stool sample analysis revealed excretion of SL3. Patient died a few weeks thereafter.
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pmc-6180649-1
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A 40-year-old Central African woman with homozygous sickle cell disease was referred for evaluation of proteinuria. During the past 5 years, her serum creatinine (Scr) level ranged from 0.35 mg/dL – 0.70 mg/dL (corresponding to estimated GFR of 126–164 mL/min/1.73m2, using the corrected CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equation for race. Five years prior to nephrology presentation, her urine albumin to creatinine ratio (ACR) was 610 mg/g; 2 months ago, it was 7779 mg/g.
At nephrology evaluation, she reported multiple vaso-occlusive pain crises as a child. She had a vaso-occlusive pain crisis and required red cell transfusion following a therapeutic abortion 5 years ago. Six emergency room visits followed for vaso-occlusive pain crises. She has proliferative sickle cell retinopathy and restrictive lung disease. Folic acid was her only medication and she took acetaminophen for a vaso-occlusive pain crisis 2 months ago.
Her physical examination revealed a non-obese woman with a blood pressure of 120/70 mmHg and heart rate 94 beats per minute and regular. She did not have any flow murmurs on precordial examination and she had bilateral ankle edema. The rest of her physical examination was normal. Laboratory investigations (Table ) revealed: Scr 0.94 mg/dL, estimated GFR, 88 mL/min/1.73m2 and hemoglobin 64 g/L. Urinalysis showed 2+ blood, 3+ protein and urine microscopy revealed 5–30 red blood cells without casts. Urine ACR is 6089 mg/g. Serologic workup revealed an anti-nuclear antibody titer of 1:320 and anti-double stranded DNA titer 72 IU/ml by ELISA. Investigations for sarcoidosis were not performed. Abdominal ultrasonography revealed that the length of both kidneys was 12 cm. She consented to kidney biopsy under ultrasonography guidance to diagnose the cause of her nephrotic syndrome.
The kidney biopsy specimen contained up to 15 glomeruli, 3 of which were globally sclerosed. There was no significant glomerular hypertrophy. Most glomeruli showed prominent nodular accumulation of amorphous, eosinophilic, weakly PAS positive, non-argyrophilic (staining properties of amyloid) material (Fig. , arrow). Congo red stain confirmed that this material exhibited the characteristic apple green birefringence of amyloid when examined under polarized light. Amyloid was type AA as demonstrated by immunohistochemistry. Amyloid extensively extended into arterioles (Fig. , arrow). There was patchy but significant deposition of amyloid in the walls of tubules with associated epithelial injury. Prussian blue stain for iron, often seen in tubular epithelial cells in sickle cell nephropathy, was negative. There was mild interstitial fibrosis and tubular atrophy. Arteries showed wall thickening by amyloid as well as multilayering of the internal elastic lamina. Immunofluorescence showed weak granular non-specific glomerular staining for IgM and C3. There was no staining for IgG, IgA, or κ and λ light chains. Electron microscopy showed deposition of non-branching randomly arranged fibrils, consistent with amyloid, predominantly in mesangial areas but also along and permeating the glomerular basement membrane. There was effacement of foot processes overlying areas with amyloid deposition (Fig. ). A diagnosis of AA type amyloidosis was made.
Perindopril 2 mg once daily was initiated to lower proteinuria, but there was concern that it was exacerbating her anemia. Perindopril was discontinued when her hemoglobin had fallen to 47 g/L and a new anti-U antibody was detected, making red cell transfusion challenging. She was subsequently admitted to hospital with acute chest syndrome and mild pulmonary hypertension was noted on two-dimensional echocardiogram. Hydroxyurea was later initiated when her hemoglobin level was 61 g/L and discontinued 2 months later when her hemoglobin had fallen to 43 g/L, due to concern that hydroxyurea may have worsened her anemia. At the last available follow-up, 1 year after initial nephrology presentation, her Scr is 1.47 mg/dL (estimated GFR 51 mL/min/1.73m2), urine ACR 7965 mg/g and hemoglobin 66 g/L. Resting blood pressure is 129/75 mmHg. She does not have clinical features of systemic lupus erythematosus (SLE). Our patient has progressive chronic kidney disease due to AA amyloidosis. Her hematologist plans to reintroduce hydroxyurea at a lower starting dose.
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pmc-6180752-1
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A 72-year-old man with a history of chronic alcoholism and cirrhosis Child score A
was referred to the oncology department of a tertiary hospital in Cali, Colombia,
for assessment of a growing mass in his oral cavity. Additionally, a mass located on
the left adrenal gland was detected during the surveillance cirrhosis controls. On
examination, an exophytic lesion of approximately 10 cm on the left mandible was
noted. He was hospitalized so laboratory tests and procedures could be performed to
establish the primary cancer diagnosis and treatment.
Serologic tests were negative for hepatitis B and C panels. Serum alpha-fetoprotein
(AFP) and carcinoembryonic antigen were not significantly altered. Abdomen magnetic
resonance imaging (MRI) and computed tomography (CT) scan showed changes consistent
with cirrhosis; no hypervascular changes or signs of hepatocellular carcinoma (HCC)
were detected (). Positron emission
tomography–CT detected abnormal hypermetabolic activity in the mandible
corresponding to the mass, pelvis bones, and adrenal mass, suggesting neoplastic
lesions, but no significant activity in the liver (). Biopsies of adrenal and mandible lesions showed morphology and
immunohistochemistry consistent with hepatoid differentiation in carcinoma. These
findings did not, however, correlate with the imaging evidence.
The history of cirrhosis along with the hepatoid characteristics of the adrenal and
mandibular tumors suggested metastatic HCC. However, the absence of a liver tumor on
imaging raised the possibility of an adrenocortical carcinoma with hepatoid
differentiation, a rare tumor with an even rarer presentation.
The patient experienced progression 1 year later despite two treatment lines. At this
time, a decision to perform an exploratory laparoscopy with liver biopsy was made.
At laparoscopy, the liver was cirrhotic and diffusely nodular without a dominant
mass. Numerous representative biopsies were taken from different areas. They
revealed histologic and immunophenotypic findings of infiltrative HCC.
Tumor markers were taken serially; initial AFP was 9.4 ng/mL (normal values, <
10.0 ng/mL), and during follow-up, AFP values were as follows: 7.3, 3.17, and 4.8
ng/mL. Carcinoembryonic antigen values were < 0.5 ng/mL (normal values,
< 3.0 ng/mL). Both tumor markers were considered nonsignificant.
The adrenal biopsy reported that no normal adrenal gland tissue was seen. Regarding
the immunohistochemical markers, the tumor was focally positive for pancytokeratin,
Hep-Par-1, and arginase-1 (Arg-1), consistent with hepatoid differentiation. The
tumor cells were negative for AFP, glypican-3, and thyroglobulin. All adrenal
markers, including inhibit, melon-A, calretinin, and podoplanin, were negative. The
proliferation index was high (Ki-67), and CD10 highlighted a canalicular pattern
within the tumor (). The mandibular biopsy
showed morphology and immunoprofile results similar to those of the adrenal tumor
(). The report concluded with a
diagnosis of oncocytic carcinoma with hepatoid features, and clinical and radiologic
correlation was recommended.
RNA in situ hybridization for albumin was performed using RNAview (Affymetrix,
Cambridge, MA) on the adrenal core biopsy and was positive, confirming hepatoid
differentiation and suggesting that the tumor was either from the liver or an
unusual hepatoid variant of adrenal cortical carcinoma.
The liver biopsy showed a neoplastic lesion composed of hepatocytic cells arranged as
tubules and rosettes. Immunohistochemistry analysis showed positive results for
cytokeratin AE1/AE3 and HePar-1. The markers C7-C20 and AFP were negative. The
proliferation index (Ki-67) was 30%. The report concluded that the histology and
immunochemistry markers were consistent with a diagnosis of HCC ().
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pmc-6180753-1
|
A 31-year-old female was found to have a 5.8-mm-deep melanoma on biopsy of a
right-side calf lesion in May 2011. She had a wide local excision and sentinel lymph
node biopsy 1 month later that showed two positive inguinal lymph nodes. A positron
emission tomography scan showed no evidence of distant disease; the patient declined
both completion node dissection and adjuvant therapy. In July 2012, she developed
multiple in-transit metastases that involved the cutaneous and subcutaneous tissues
in the right-side thigh. Her tumor was found to harbor a BRAF V600E
mutation, and she started vemurafenib treatment. The patient had a partial response,
but by June 2013, the disease progressed with three new lesions on the lateral
right-side thigh and knee. No distant metastases were present on imaging. She began
treatment with ipilimumab 3 mg/kg every 3 weeks on June 28, 2013, with her third
dose delayed until September 9 as a result of grade 1 diarrhea. Because of an
increase in the number of in-transit lesions by August 30, the patient also received
biweekly intralesional aldesleukin (interleukin 2) injections of 9 million
International Units total dose each on five occasions during September. Aldesleukin
was added in the hope of synergistic efficacy and caused no significant adverse
effects.
Although the patient was told to avoid pregnancy, she discovered she was pregnant
after her third dose of ipilimumab. Ultrasound confirmed a pregnancy of 6 weeks
gestation. She was counseled about potential clinical benefits and risks of
congenital malformations to the fetus from ipilimumab and interleukin 2; she
declined termination for religious reasons. The patient and her physician decided to
proceed with a fourth dose of ipilimumab in October; the patient then received eight
additional doses of low-dose intralesional aldesleukin, which finished in November.
At that point, her physician believed the risks to the fetus of additional
aldesleukin outweighed the possible benefits. The patient had negative chest x-ray
results on February 7, 2014; otherwise, the status of her in-transit disease was
assessed clinically without imaging during her pregnancy because the disease was
visible or palpable. By February 14, progressive disease was evident and she had
five in-transit metastases (5 to 12 mm in size) surgically removed. Thyroid test
results during and after immunotherapy were normal. The patient had no autoimmune
adverse effects from ipilimumab other than grade 1 diarrhea.
She delivered a healthy male infant on May 21, 2014. No special assessment of the
placenta was done for metastatic disease. Routine follow-up of her child at 2 3/4
years of age showed a healthy boy with no physical or developmental abnormalities
and no history of unusual infections. Detailed testing of the child’s immune
system has not been performed.
After delivery, the patient was found to have new large metastases to her right-side
inguinal and iliac lymph nodes and a recurrent in-transit metastasis. In June 2014
she was started on pembrolizumab, but unfortunately had further progression of
disease with distant metastases in 2016.
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pmc-6180757-1
|
A 68-year-old man, a former smoker (35 pack-years) with an Eastern Cooperative
Oncology Group performance status of 1, received heart transplantation for dilated
idiopathic cardiomyopathy in 2012, followed by continuous immunosuppressive
treatment with tacrolimus 2 mg/day and mycophenolate mofetil 720 mg/day.
In March 2016, this patient presented with symptoms of cough, weight loss, hyporexia,
and dyspnea. Initial work-up demonstrated a 3.1 × 2.3–cm posterior
left upper lobe mass, multiple bilateral lung micronodules, as well as several
enlarged lymph nodes (ipsilateral hilum, bilateral upper paratracheal, and
para-aortic sites). Pulmonary transbronchial biopsy revealed an adenocarcinoma
(). 18F-labeled
fluorodeoxyglucose positron emission tomography showed increased uptake in primary
mass, enlarged lymph nodes, and lymphangitic carcinomatosis (T2aN3M1a).
A next-generation sequencing gene panel (TruSight 26-gene panel; Illumina, San Diego,
CA) revealed a deletion in exon 19 of EGFR (p.Glu746_Ala750del),
with no abnormalities in ERBB2, BRAF,
KRAS/NRAS, MET, or
PIK3CA; ALK translocations were not detected by
immunohistochemistry ().
This patient was administered erlotinib 150 mg/day concomitant with his
immunosuppressant medications. The treatment was well tolerated, with only grade 1
skin toxicity after 3 weeks of erlotinib administration. After 5 weeks of treatment
with erlotinib, the patient developed left pleural effusion, requiring thoracentesis
and pleurodesis with immediate clinical improvement. After 7 weeks, a computed
tomography scan showed progressive pleural, parenchymal, and mediastinal disease;
chemotherapy with carboplatin and pemetrexed was started (). No dose reduction or discontinuation was required. As of
this writing, the patient presented with a partial response to chemotherapy and is
receiving pemetrexed maintenance therapy.
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pmc-6180761-1
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A 26-year-old man with known G6PD deficiency presented at the hospital in November
2016 complaining of right testicle enlargement for the past 2 months without other
significant symptoms. A scrotal ultrasound was performed and showed a testicle of
increased size (27.3 cm3) with diffuse heterogeneity. A computed
tomography scan of the chest, abdomen, and pelvis revealed multiple lung nodules up
to 28 mm and thoracic and retroperitoneal lymph nodes suggestive of advanced germ
cell tumor. Serum tumor markers were obtained: alpha fetoprotein, 71.8 ng/mL (normal
range, up to 8.0 ng/mL); human chorionic gonadotropin (hCG), 2,003 mUI/mL (normal
range, inferior to 5.0 mUI/mL), and lactate dehydrogenase, 546 UI/L (normal range,
120 to 246 UI/L).
The patient underwent a right inguinal orchiectomy on November 24, 2016, and the
pathologic report was consistent with nonseminomatous germ cell tumor (NSGCT) in the
form of embryonal carcinoma (immunohistochemistry: carcinoembryonic antigen,
negative; hCG, negative; cancer antigen 125, negative; placental alkaline
phosphatase, positive; C-KIT, negative; AE1 to AE3, positive; calretinin, negative;
CD30, positive). Post-orchiectomy serum tumor markers were as follows: alpha
fetoprotein, 159.4 ng/mL (normal range, up to 8.0 ng/mL); hCG, 2,661.3 mUI/mL
(normal range, inferior to 5.0 mUI/mL); lactate dehydrogenase, 482 UI/L (normal
range, 120 to 246 UI/L).
In the face of the findings of intermediate-risk NSGCT according to the International
Germ Cell Cancer Collaborative Group classification, systemic therapy was proposed
with bleomycin, etoposide, and cisplatin (BEP) for four cycles, which is the
standard-of-care therapy in this setting. Considering the known G6PD deficiency, an extensive search
of the literature was performed regarding the safety of chemotherapy drugs in this
scenario, but almost no data were found. G6PD was dosed (33.1 mU per billion
erythrocytes [normal, > 118 mU per billion erythrocytes]), and activity was
consistent with moderate deficiency. A geneticist was consulted, and after
considering risks and benefits, chemotherapy was started on December 1, 2016, with
the patient on the oncology ward under rigorous daily surveillance.
Despite the fear of acute hemolysis, laboratory analysis showed no remarkable
variations of hemoglobin levels throughout the four cycles of BEP, as shown in . The patient received standard doses of
chemotherapy without any other special precaution except for adequate intravenous
hydration. After the first cycle of BEP, he presented with deep venous thrombosis of
a peripherally inserted central venous catheter in the right arm, but treatment was
otherwise well tolerated. The patient had a complete response to chemotherapy, as
seen by tumor markers () and imaging
studies (- and -). The patient returned for follow-up in late March 2017 with
no evidence of disease and will be observed regularly with serum tumor markers and
computed tomography scans as per protocol for testicular germ cell tumors.
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pmc-6180791-1
|
A 60-year-old African American man with a medical history of hypertension, alcoholic
cirrhosis, chronic obstructive pulmonary disease, and recent diagnosis of chronic
eosinophilic leukemia (CEL) was transferred to our hospital for fever, elevated WBC
count of 61,000/mm3, and urinary tract infection symptoms. Two months
earlier, he was admitted to an outside hospital with severe fatigue, low appetite,
and weight loss. During that admission, he was found to have an elevated WBC count
of 50,000/mm3, with a differential showing 22% neutrophils, 21%
lymphocytes, 46% eosinophils, and 2% basophils. The hemoglobin level was 9.1 g/L,
and the platelet level was 70,000/mm3 (). Bone marrow examination performed at the referring institution
revealed a markedly hypercellular bone marrow (100% cellularity), involved by a
myeloid neoplasm with marked eosinophilia and approximately 15% CD34-positive blasts
on core sections; a standard differential performed on the aspirate smears revealed
approximately 8% blasts. In addition, it showed marked myeloid hyperplasia,
including an increased number of atypical eosinophils, dysgranulopoiesis, and fewer
erythroid precursors (). Flow cytometric
analysis performed on the aspirate revealed increased myeloblasts (11% of total
events) and a marked increase of eosinophils (54%). Fluorescent in situ
hybridization testing was significant for a translocation of
PDGFRA/4q12, and metaphase cytogenetics revealed an abnormal
male karyotype, 46,Y,t(X;5)(p11.4;p15.3)[6]/46,XY. Additional fluorescent in situ hybridization studies
performed at our institution on a subsequent bone marrow examination confirmed the
PDGFRA rearrangement; in addition, the recurrent cytogenetic
abnormalities associated with acute myeloid leukemia t(15;17), t(8;21), and inv(16)
were all excluded. Reportedly, the patient started receiving oral imatinib 400 mg
daily at the outside hospital for 3 to 4 weeks, but it had to be discontinued
because of severe pancytopenia. We reviewed all the outside hospital hematology
notes to learn why the patient was receiving oral imatinib 400 mg daily; however we
could not find the answer to this question.
On arrival at our hospital, the patient was confused, afebrile, and tachycardic, with
physical examination notable for temporal wasting, 3+ pitting edema in his feet
bilaterally, a distended but nontender abdomen with splenomegaly, and a stage 3
sacral decubitus ulcer. There were no palpable enlarged lymph nodes or skin rashes.
The patient denied nausea, vomiting, diarrhea, constipation, easy bleeding or
bruises, abdominal pain, and fevers. The presenting CBC and chemistries were as
follows: WBC, 59,000/mm3 with marked eosinophilia; hemoglobin, 9 g/L;
platelet count, 11 × 103/mm3; creatinine, 1 mg/dL;
potassium, 3.8 mEq/L; sodium, 139 mEq/L; blood urea nitrogen,18 mg/dL; phosphorus,
2.1 mg/dL; and calcium, 7.8 mg/dL. A complete abdominal ultrasound revealed moderate
splenomegaly, with a calculated splenic volume of 1,318 mL, a moderate amount of
ascites, and normal sonographic appearance of the liver without intrahepatic or
extrahepatic ductal dilation.
Blood and urine cultures were taken, a platelet transfusion was given, and the
patient was given intravenous ceftriaxone and fluids because the urine culture taken
3 days earlier at the outside hospital revealed Klebsiella species.
Once the patient improved clinically, he received imatinib 400 mg daily by mouth for
his myeloid neoplasm with eosinophilia and PDGFRA rearrangement.
After 2 days of imatinib treatment, the WBC count decreased to
36,000/mm3, the creatinine level went up to 1.6 mg/dL, the uric acid
level was 14.4 mg/dL, the potassium level was 6 mEq/L, the phosphorus level was 7.1
mg/dL, the calcium level was 7.2 mg/dL, and the lactate dehydrogenase level was 369
U/L. These laboratory abnormalities were compatible with tumor lysis syndrome (TLS),
and the patient was given rasburicase (Elitek; Sanofi, Brightwater, NJ), allopurinol
(Zyloprim; Prometheus Laboratories, San Diego, CA), sodium polystyrene sulfonate
(Kayexalate; Sanofi), and aggressive hydration (). Two days later, the creatinine level decreased to 0.9 mg/dL,
the uric acid level decreased to 7.6 mg/dL, the lactate dehydrogenase level
normalized, and the WBC count decreased to 5,000/mm3. Imatinib was
decreased to 200 mg daily. The patient stayed in the hospital for 2 weeks for
treatment of his acute urinary tract infection, up-titration of furosemide and
spironolactone, and stabilization of his portal hypertension. He tolerated the
low-dose imatinib well without requiring blood transfusions.
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pmc-6180806-1
|
Our patient was a 66-year-old woman who presented with a reported 6-month history of
an enlarging ulcerating mass replacing the entire left breast, with drainage of
purulent, foul-smelling fluid. A diagnosis of invasive carcinoma of the left breast
was confirmed on core biopsy. The tissue sample underwent immunohistochemical
testing, which did not reveal the overexpression of estrogen or progesterone
receptors. However, the pathologic testing did reveal overexpression of the HER2/neu
protein. Physical examination revealed left-sided supraclavicular and bilateral
axillary lymphadenopathy, and a positron emission tomography scan revealed widely
metastatic disease of the lungs, liver, and bone. The patient received a right
internal jugular vein portacath and palliative chemotherapy, which was initiated
with PTH 5 days after port insertion. Three weeks after the first chemotherapy
administration, there was dramatic regression of the left breast lesion ( and ), as illustrated by pictures taken before and after treatment.
At the time of administration of the first chemotherapy cycle, blood had been
aspirated from the port before infusion. When the patient returned to the
chemotherapy infusion center for her scheduled second cycle of PTH, the nursing
staff was unable to aspirate blood from the port, but, because it flushed without
difficulty, it was used for the second infusion of PTH. The patient once again
tolerated the infusion with no unusual symptoms. On her third cycle of chemotherapy,
aspiration from the port produced a clear yellow liquid. The patient was sent to the
radiology department for assessment of the port. A chest x-ray was obtained, and the
position of the port was reported as normal, but a new pleural effusion was noted. A
subsequent venogram study showed flushing of intravenous (IV) contrast from the
catheter into the right pleural cavity. The intrapleural position of the catheter
was confirmed by chest computed tomography scan, and it was apparent that the first
two doses of the PTH regimen had been administered directly into the right pleural
cavity. The patient was taken to the operating room the next day, and the portacath
was removed, with thoracoscopic observation. The catheter was noted to enter the
right pleural cavity via a perforation at the junction of the right subclavian vein
and the superior vena cava (). There was
no bleeding from the vein on removal of the portacath, and the pleural fluid was
drained. Of note, there were no pleural adhesions observed during the thoracoscopic
examination.
The patient was clinically stable after the incident and was able to resume the PTH
regimen as scheduled. She was restaged with a computed tomography scan of the
thorax, abdomen, and pelvis after the third cycle of PTH, and the results revealed
significant improvement in the disease burden of the thoracic cavity; however,
disease progression was noted in all other known sites.
|
pmc-6180807-1
|
A 65-year-old woman visited our outpatient department with a complaint of weight loss
for 1 year. She was in good general condition and had an Eastern Cooperative
Oncology Group performance status of 1. Abdominal examination revealed an enlarged
liver that was palpable 6 cm below the right costal margin; it was not tender and no
other mass was felt. A complete hemogram as well as liver and renal function tests
were normal. The coagulation profile was normal. Levels of carcinoembryonic antigen
(1.94 ng/mL) and alpha-fetoprotein (2.13 ng/mL) were within the normal range.
Contrast computed tomography (CT) of the abdomen at presentation () revealed a large heterogeneous mass (18
× 12 × 12 cm) involving the entire right hepatic lobe (anterior and
posterior segments), displacing hepatic veins and the inferior vena cava. The mass
showed multiple nonenhancing areas, which were suggestive of necrosis. A tiny
calcification was found in the periphery of the lesion. Two small hypodense areas
were found on the left hepatic lobe, which was suggestive of simple cysts. The mass
showed early arterial enhancement, which is usually noticed in vascular lesions.
Ultrasound-guided fine-needle aspiration cytology of the liver was done twice and
both times it showed blood and tiny fragments of the liver with few dilated vascular
channels. Because biopsy was unsuccessful, a provisional diagnosis of HCC was
established on the basis of radiologic findings.
The mass was considered inoperable because it involved all three hepatic veins and
the right branch of the portal vein. Therefore, with a presumptive diagnosis of HCC,
the decision was made to start sorafenib at a dosage of 800 mg per day. The patient
developed grade 2 hand-foot syndrome, which was observed approximately 1 month after
administration of sorafenib and subsequently settled down after tapering and
adjusting the dosage to 200 mg per day. This was the dose that the patient could
tolerate. Sequential ultrasonography of the abdomen after 5 months of treatment with
sorafenib revealed a 40% size reduction; hence the same dose of sorafenib was
maintained.
A repeat CT scan after 18 months of regular treatment with sorafenib revealed
remarkable tumor size reduction with atrophy of the right lobe of the liver (). The tumor measured 10.8 × 9.8 cm.
There was compensatory hypertrophy of the left lobe of the liver. The left lobe cyst
appeared static. Because the CT scan showed that the tumor had undergone significant
reduction and was operable, a right hepatectomy was planned for the patient.
A positron emission tomography–CT scan was performed, which confirmed an
irregular lobulated mass in the right lobe of the liver involving segments 5, 6, and
7 (size: 8.1 cm [anteroposteriorly] × 9.2 cm [width] ×10.8 cm
[craniocaudally]), with increased metabolic activity (standard uptake value, 3.2)
and a tiny non–[18F]fluorodeoxyglucose-avid simple cyst in the
left lobe of the liver. There was no uptake elsewhere in the body.
The general health of the patient was fit on the basis of other routine
investigations required for the surgery. Right hepatectomy was performed. The
intraoperative findings were that there was a necrotic friable tumor in the right
lobe of the liver with autodemarcation of the right and left lobes. The portal triad
was free of tumor.
The postoperative surgically resected specimen was later reported as a hemangioma
(). Sorafenib was then discontinued.
The patient is asymptomatic and regular clinical follow-up is ongoing.
|
pmc-6180814-1
|
A 68-year-old Japanese woman was referred for evaluation to our service in September
2013; she complained of abnormal uterine bleeding. She was 10 years postmenopausal,
nulliparous, and otherwise healthy except for a corneal transplantation in her right
eye in 2002.
She underwent a few investigational examinations, and her transvaginal ultrasound
showed an abnormally thickened endometrium. In the hysteroscopy, she had an enlarged
uterus with an irregular endometrial lining and a few uterine polyps that bled
easily. The endometrial biopsy was consistent with an endometrial adenocarcinoma,
histologic grade 1, nuclear grade 2, and neoplastic myometrium infiltration.
Her pelvic magnetic resonance imaging (MRI) results showed uterine myomas and a thick
and heterogenic endometrium that measured 1.2 cm. The chest computed tomography (CT)
scan had multiple bilateral nodules that were randomly distributed in both lungs,
which was suggestive of metastatic disease. A CT-guided biopsy of one of the
pulmonary nodules was performed, and the histologic result was metastatic
endometrial adenocarcinoma. The immunohistochemistry was β-catenin negative,
thyroid transcription factor 1 negative, progesterone receptor and estrogen receptor
positive, vimentin negative, CK7 positive, and carcinoembryonic antigen
negative.
To control the uterine bleeding, megestrol acetate 160 mg daily was prescribed in
December 2013; however, the bleeding did not stop completely, so the patient
underwent a total hysterectomy for local control in February 2014. The pathologic
analysis of the uterus confirmed an endometrial adenocarcinoma, moderately
differentiated, histologic grade 1, with infiltrations of more than two-thirds the
depth of the myometrium and with vascular invasion. The final pathologic staging was
pT1bNxM1.
Also in February 2014, the patient underwent an abdominal and pelvic MRI () that indicated the presence of highly
vascularized liver nodules that were localized mostly in the right lobe, had lack of
perfusion in the adjacent parenchyma, and measured approximately 0.8 cm. These
lesions did not appear to be metastatic nodules, and vascular abnormalities were
considered.
At this time, her physical exam and the results of routine laboratory investigations,
including liver enzymes, were unremarkable, so we decided to proceed with a
conservative approach of regular follow-up visits. The patient continued to take
megestrol acetate 160 mg daily and remained asymptomatic.
An abdominal MRI was repeated every 3 months, and the liver nodules did not change in
number or size until March 2015, when the MRI indicated growth of the nodules from
0.8 cm to 1.4 cm. At this time, a percutaneous needle biopsy of one of the liver
nodules was done. The histologic result showed a cystic lesion filled with
erythrocytes throughout the lobule, with moderated sinusoidal dilatation and atrophy
of the adjacent hepatocytes. The portal space had a few lymphocyte infiltrations,
and there was no fibrosis or any malignancy in this sample. The final pathologic
diagnosis was peliosis hepatis. Megestrol acetate is associated with peliosis
hepatis, so the patient was prescribed anastrozole 1 mg daily instead in April
2015.
The patient remains asymptomatic and undergoes a repeat abdominal MRI every 3 months.
The last evaluation was in July 2016, and the hepatic nodules were stable.
|
pmc-6180815-1
|
A 20-year-old male presented with knee pain that increased in intensity at night. The patient had a history of an OBL of the posterior spinal column treated 5 years ago. The OBL was diagnosed through a CT scan and an MRI that demonstrated an osteolytic lesion of the second lumbar vertebrae. The CT scan revealed a 2-–3 cm ovoid lesion in the posterior arch of the second lumbar vertebrae and an MRI of the lumbar spine confirmed a reactive, hypointense soft-tissue swelling in T
1 with a mildly increased T
2 signal (). The patient was treated with curettage and the histological diagnosis was OBL.
At the time of our examination, we reviewed the histological slides of the previous diagnosis and the diagnosis of an OBL was confirmed (). The patient presented with knee pain identical in character to the pain associated with the previous OBL of the spine. The knee pain was almost constant and had the typical tendency to increase in intensity during the night; it was relieved by non-steroidal anti-inflammatory drugs. There was no limitation of movement of the knee and no neurovascular deficit. The CT scan showed a small nidus without sclerosis and the MRI confirmed the nidus with an inflammation of the surrounding tissue (). The bone scintigraphy, performed to rule out more lesions, showed increased activity in the left distal femur. Before starting radiofrequency ablation (RFA) treatment, a biopsy sample was obtained using the Bonopty set (Radi MS, Uppsala, Sweden). With the patient under spinal anesthesia, a core-needle biopsy was performed under CT guidance. Then, we placed the needle electrode inside the nidus (monopolar, non-refrigerated; SMK, Radionics, Burlington, MA), and RFA was performed through the same tract with a 5-mm radiofrequency probe heated to 90 °C for 5 min, using the radiofrequency generator (RFG-3C; Radionics) (). The diagnosis was an OO (). After a few days, the patient was completely asymptomatic and at the time of the most recent follow-up (1 year after treatment), the patient remained symptom free.
|
pmc-6180816-1
|
The patient was a 63-year-old male with adenocarcinoma of the rectosigmoid junction and multifocal tubular adenoma of the right colon. The patient underwent right hemicolectomy and 6 cycles of folinic acid (also called leucovorin, FA or calcium folinate)/fluorouracil (5FU)J/oxaliplatin (FOLFOX).
Findings: Post-therapy positron emission tomography (PET)/CT scan showed bilateral symmetric hilar and mediastinal enlarged lymph nodes with increased 18-fludeoxyglucose (FDG) activity (). The maximum standardized uptake value (SUV max) of the subcarinal lymph node was 11.7, SUV max of the right hilar lymph nodes was 10.6 and that of the left hilar lymph nodes was 9. There were no lung abnormalities to suggest active infection or inflammation. Biopsy of one of these lymph nodes was consistent with sarcoid-like reaction (SLR).
|
pmc-6180816-2
|
The patient was a 45-year-old female with multifocal multicentric left breast cancer, mcT2N0M0, Stage 2A, oestrogen receptor/progesterone receptor+, human epidermal growth factor 2(−). The patient had chemotherapy followed by left mastectomy and reduction of the right breast. She completed radiation therapy afterwards and started chemotherapy.
Findings: PET/CT scan after completion of radiation therapy revealed hypermetabolic symmetric hilar lymph nodes (). SUV max of the right hilar lymph nodes was 8.6 and SUV max of the left hilar lymph nodes was 8.5. There were no lung findings to suggest active infection. Upon review of the history with the patient’s oncologist, this appearance was accepted as most consistent with SLR. Follow-up PET/CT scan revealed interval resolution of hypermetabolic lymph nodes ().
|
pmc-6180816-3
|
A 57-year-old male with non-Hodgkin’s lymphoma presented initially with a left lower extremity swelling. The patient was found to have a large mass in the left iliac wing and was diagnosed with diffuse B-cell lymphoma. The patient underwent 6 cycles of rituximab and Cytoxan (cyclophosphamide)/Adriamycin (hydroxy doxorubicin)/vincristine (Oncovin)/prednisone (also known as CHOP).
Findings: Initial PET/CT showed a lytic hypermetabolic mass in the left iliac wing with left pelvic hypermetabolic adenopathy (). Biopsy of the bone lesion revealed diffuse B-cell lymphoma. The first post-treatment PET/CT scan performed 8 months after completion of therapy showed a complete "metabolic" response (). The second follow-up PET/CT scan 2 years after completion of therapy demonstrated new mediastinal/hilar hypermetabolic adenopathy (). SUV max of the precarinal lymphadenopathy was 18.7, subcarinal lymphadenopathy was 26.3 and that of the right hilar lymph nodes was 24.6. Biopsy of one of these lymph nodes revealed non-caseating granulomatous inflammation. The third follow-up PET/CT scan after 2 years showed new abdominal hypermetabolic adenopathy () with SUV max of 8.7. The last follow-up PET/CT performed 2 years after the third follow-up PET/CT scan showed almost complete improvement of these findings (). The patient did not receive any therapy after the first follow-up PET/CT scan. The second to last follow-up PET/CTs were acquired to monitor SLR-related findings. There was spontaneous resolution of FDG activity of these nodes, thus it was not a treatment-induced tumour response.
|
pmc-6180818-1
|
We present a case of spontaneous reduction in size of a perineal and pelvic AA in a 50-year-old female patient observed during a 6-month period of HRT withdrawal and well assessed using 3T MRI. The patient was referred to our hospital by the gynaecologist to undergo a pelvic MRI because of worsening back pain and vague pelvic discomfort.
She previously underwent a radical hysteroannessectomy (for uterine fibromas and an endometrial/mucinous cyst on the left ovary) and a transurethral resection of the bladder (for a low-grade papilloma), 5 and 2 years earlier, respectively. After the hysteroannessectomy, the patient was treated with HRT (with a transdermal gel formulation for the first year and then oral tablets at a daily dose of 1 mg).
MRI protocol, performed with a 3T magnet (Verio, Siemens AG, Erlangen, Germany) using 8-channel surface coil, included T
2 weighted images on three planes: axial fat-suppressed T
2 weighted sequences, axial and coronal fat-suppressed T
1 weighted sequences before and after contrast media injection (1 ml kg–1 of gadobenate dimeglumine, MultiHance, Bracco, Milan, Italy) and diffusion weighted sequences (DWI).
MRI revealed a well-defined, 9 × 5-cm mass lesion arising from the right perianal fat tissue. The lesion displaced contralaterally the anal canal and the vagina, whereas the bladder was markedly compressed. Sagittal T
2 weighted sequence showed a “finger-like” extension of the lesion into the right ischiorectal fossa; signs of infiltration of the right elevator ani muscle were also observed. The lesion was quite homogeneously isointense in comparison to muscle on T
1 weighted images. On T
2 weighted and fat-suppressed T
2 weighted images, the lesion mainly showed high signal intensity, with layered wave-like strands of lower signal intensity. The mass markedly enhanced after contrast media administration, with a “swirling” pattern. DWI showed heterogeneous high signal intensity on B0 and B1000 sequences; apparent diffusion coefficient (ADC) mapping showed a high value in the tumour (). Based on peculiar localization and MRI findings, radiologists suggested the diagnosis of AA.
A CT-guided biopsy with a Tru-Cut 16G needle with a perineal approach was performed; pathologists definitively confirmed the diagnosis of AA. The tumour histologically consisted of spindle cells in a myxoid stroma, containing a mixture of thick- and thin-walled blood vessels with interposition of normal fat tissue (). Immunohistochemically, the tumour cells exhibited diffuse nuclear positivity with ER.
Radical surgery was not thought to be feasible; the therapeutic decision, on the basis of hyperexpression of ER, was to suspend HRT in order to reduce the oestrogen stimulation and hence cell proliferation. A short-term MRI follow-up was planned.
6 months later, the patient came back to our department owing to regression of symptoms and underwent a new MRI scan that revealed a marked reduction in size of the tumour (about 60–70% in volume); bladder compression and surrounding structures’ infiltration were also reduced. Post-contrast fat-suppressed T
1 weighted images showed a reduction in the lesion’s vascularization. On DWI sequences, AA remained hyperintense on both B0 and B1000 images and ADC map ().
|
pmc-6180826-1
|
A 66-year-old female with a history of breast and lung cancer, both treated and in remission, presented with new onset of generalized abdominal pain. Physical examination and laboratory work-up were unrevealing as to a potential cause.
|
pmc-6180828-1
|
In a work-up of a 40-year-old female with a history of low back pain, a routine MRI of the lumbar spine identified an incidental lesion. The axial T
1 weighted image showed a 21-mm round, homogeneous lesion of low signal intensity interforaminally in the left S2 segment of the sacrum. The axial short tau inversion-recovery image showed a well-defined lesion with an inhomogeneous signal intensity throughout the lesion with high peripheral rim intensity. The axial T
1 image with fat saturation after contrast media injection showed moderate enhancement throughout the lesion and in the peripheral rim (). A radiograph of the pelvis was performed to further characterize the lesion. On clinical examination, the sacral area was not painful to palpation. Owing to the atypical appearance of the lesion and the non-specific nature of the MRI signal pattern, a bone scan was performed that showed a solitary lesion on the left side of the sacrum with increased metabolic activity. For further characterization, and in the search of a potential primary tumour, positron emission tomography (PET)-CT was performed, which showed a well-defined sclerotic lesion with mild fludeoxyglucose (FDG) avidity (average standardized value 2.5) in the S2 segment and no other abnormalities (). Owing to the metabolic activity of the lesion, the patient was referred to the orthopedic oncology department for image-guided biopsy of the lesion. The biopsy specimen consisted of a few small fragments of bone marrow, some skeletal muscle, fibroadipose tissue and blood clots. Infiltration of the otherwise normal bone marrow with scattered small groups of big foamy cells was identified (). The foamy cells had vacuolated cytoplasm and small centrally located nuclei. The cells were negative for cytokeratin AE1/AE3, CD68, barchyury, Melan A, HMB 45, desmin and smooth muscle actin but positive for S100 protein (). The cells contained multiple lipid droplets and numerous large mitochondria; the existence of the latter was exhibited with antimitochondrial marker (). A pathological diagnosis of hibernoma was made in correlation with the imaging findings.
Owing to the clinical assessment in correlation with the history of bilateral lumbago, worse after physical activity, the patient was diagnosed with chronic lower back pain. At 1-year follow-up, the patient was being managed with analgesics and physical therapy.
|
pmc-6180829-1
|
An 8-year-old autistic male presented to the emergency department with severe bilateral leg pain and difficulty walking. Additional recent medical history included gum swelling and bleeding, low-grade fever and a maculopapular rash in bilateral upper and lower extremities. Routine blood work, additional tick titres and autoimmune workup were all normal. A clinical diagnosis was unclear and a whole-body bone scintigraphy examination was ordered followed by subsequent radiographs. Bone scintigraphy demonstrated increased radiotracer activity in bilateral shoulders, wrists, hips, knees and ankles, most severe in the knees (). Radiographs of the above-mentioned areas were all normal (). Differential considerations included infiltrative processes such as leukaemia, neuroblastoma metastases and multifocal osteomyelitis. Multifocal fractures were felt to be unlikely. Further evaluation with MRI was recommended. Subsequent contrast-enhanced MRI of both femurs demonstrated intense metaphyseal signal abnormality and enhancement in bilateral proximal and distal femurs and proximal tibiae (). Subperiosteal signal abnormality and enhancement along the metaphysis of both femurs and tibiae was also observed (). MRI findings correlated with findings seen on whole-body bone scintigraphy but were occult on radiographs. An infiltrative process such as leukaemia was of primary concern.
Following MRI, a peripheral blood smear and a bone marrow aspiration were obtained to evaluate for haematological malignancy; both were negative. Urine and blood cultures were obtained and both were normal. Perplexed by the abnormal imaging findings and normal laboratory work-up, further discussion with the patient’s mother revealed that the patient’s diet consisted solely of cookies, brown sugar pop tarts, chocolate milk and Krispy Kreme doughnuts. Nutritional deficiency was considered the cause of the patient’s symptoms and a complete vitamin panel was ordered that revealed a low vitamin C level of 0.1 mg dl-–1 (normal 0.4–2.0 mg dl–1). All other vitamins were normal. A clinical diagnosis of vitamin C deficiency or scurvy was established.
Treatment consisted of corrective nutritional measures and supplemental vitamin C therapy. The patient’s symptoms rapidly improved and he was discharged home and instructed to take 100 mg of supplemental vitamin C twice a day. After approximately 8 months of supplemental vitamin C therapy, the patient returned for a follow-up MRI of both femurs. Metaphyseal abnormalities seen on initial MRI had completely resolved on the follow-up MRI examination ().
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pmc-6180830-1
|
OD is 28-year-old premenopausal, para 1 +0 Yoruba female who presented at the age of 28 years for sonographic examination of a recurrent left breast mass. She underwent a lumpectomy 3 months earlier at another tertiary facility with a histological diagnosis of invasive ductal carcinoma (IDC) of the excised mass. She has a strongly positive family history of breast cancer in first-degree relatives (her mother and maternal grandmother). The details of presentation and the death of her grandmother were not disclosed. However, her mother was diagnosed at the age of 52 years and died 6 years later of the disease. The patient presented with bloody left nipple discharge. A clinical breast examination was performed before sonomammography. This revealed a scar at the upper outer quadrant of the left breast, consistent with the site of the previous lumpectomy. There was a palpable, firm retroareolar mass in the same breast that was fairly mobile with associated thickening of the areola. There was also bloody nipple discharge and ipsilateral axillary lymphadenopathy. At the time of the examination, the right breast was essentially within normal limits.
Left sonomammography performed at the Radiology Department, UCH, with the Logiq P5 GE ultrasound machine (GE Healthcare, Waukesha, WI) using the high frequency linear transducer (10 MHz) showed a mixed density mass with specks of calcifications at the 3 o’clock position and in the retroareolar region. The overlying areola was thickened and there was architectural distortion from the previous scar. Also, there were two axillary lymph nodes with fatty replaced hila. A final BI-RADS assessment of category 5 (highly suggestive of malignancy) was made, with possible invasion of the ipsilateral axillary nodes. An immediate ultrasound-guided core biopsy of the mass was performed and histological examination confirmed IDC, Scarff–Bloom–Richardson grade 2, score 6; the immunochemistry result was triple-negative.
She was immediately commenced on four courses of adriamycin and cyclophosphamide neoadjuvant chemotherapy and later had left modified radical mastectomy. She also had four courses of radiotherapy and paclitaxel adjuvant chemotherapy a few months after the left mastectomy.
She made progress and resumed work. She also got married 2 years later and became pregnant immediately after. During cyesis, she developed another lump on the contralateral side. A breast ultrasound was performed and showed evidence of architectural distortion at the 6 o’clock position but no definite intramammary mass was seen. There were, however, enlarged ipsilateral replaced axillary nodes. An impression of a contralateral tumour was made and a final BI-RADS category of 4c was assigned to the study. An immediate ultrasound-guided core needle biopsy (CNB) of the suspicious area revealed malignant features (). She, however, declined chemotherapy until after the delivery of her baby; she was admitted for close monitoring, further investigations and palliative care. At term, she was delivered of a normal male infant by spontaneous vaginal delivery. Unfortunately, she could not breastfeed the baby as she re-presented 4 weeks after delivery at the Accident and Emergency Unit, UCH, owing to weight loss, breathlessness and progressive non-productive cough of 2 weeks’ duration. Further investigations at the time showed widespread canon-ball opacities consistent with metastases in both lung fields with bilateral pleural effusion consistent with pulmonary metastasis. A bone scan also confirmed widespread bone metastasis. Abdominopelvic ultrasound found metastasis to the liver. An impression of a rapidly progressing disease was made.
During the most recent admission, she was initially managed conservatively, counseled on family planning and offered six courses of adjuvant chemotherapy. It is important to note that, throughout her management, she enjoyed the strong social support of her family members and her husband.
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pmc-6180830-2
|
KA is a 50-year-old premenopausal parous female who presented for imaging at the age of 45 years with a history of a right breast lump of 6 months’ duration. She has no positive family history of breast cancer.
Right sonomammography performed at the Radiology Department, UCH, with a Logiq P5 GE ultrasound machine using the high frequency linear transducer (10 MHz) at her first presentation showed a poorly circumscribed mixed echogenic mass at the 12 o’clock position measuring 4.9 × 3.2 cm. The mass showed specks of calcifications within it. The Doppler interrogation showed evidence of increased vascularity. A final BI-RADS category of 4 (suspicious for malignancy) was assigned to the study (). Conventional mammography performed in the same department confirmed a poorly defined mass with microcalcifications and architectural distortion at the 12 o’clock position. The left breast at the time of the study was normal on both imaging modalities. She subsequently had an ultrasound-guided CNB of the right breast lump and the histopathological report confirmed IDC (). The immunochemistry report was triple-negative. She immediately commenced neoadjuvant chemotherapy and later had modified right radical mastectomy. After surgery, she had adjuvant chemo- and radiotherapy. She was a compliant patient who had remission for approximately 5 years; during this period, she was off chemotherapeutic drugs.
She developed a painless progressive lump in the contralateral breast 5 years later and presented to the surgical outpatient clinic. On examination, there was a palpable left breast mass with associated bloody nipple discharge, which was confirmed on sonomammography. Histological examination of the ultrasound-guided CNB specimen of the contralateral mass confirmed it to be an IDC. She then had modified left radical mastectomy after adjuvant chemotherapy and has since been placed on paclitaxel and radiotherapy.
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pmc-6180830-3
|
OA is a 36-year-old premenopausal para 2 + 0 Yoruba female who presented in 2013 at the General Outpatient Department, UCH, owing to a palpable painless right breast lump of 3 years’ duration. She had a positive family history of breast cancer in a first-degree relative (her mother) who was diagnosed at the age of 45 years and died at the age of 55 years. At presentation, she was found to be lactating and there was a firm, non-mobile nodular mass in the lower outer quadrant (LOQ) of her right breast. A similar but smaller mass was palpated in the left breast. There were no associated skin changes or nipple retraction.
Because she was lactating, a conventional mammography could not be performed; however, a sonomammography was requested and this was performed at the Radiology Department, UCH, with a Logiq P5 GE ultrasound machine using the high frequency linear transducer (10 MHz) and it confirmed bilateral disease. The lesions found were two poorly circumscribed hypoechoic masses with spiculated margins in the LOQ at the 6- –9 o’clock position of the right breast; one deep in the prepectoral region and the other superficial in the middle ring of the right breast between the 6 and 8 o’clock position. They measured 4.3 × 2.9 cm and 1.4 × 1.3 cm, respectively. The latter mass showed specks of calcifications within it. Both masses in the right breast showed posterior acoustic shadows. There was also associated architectural distortion. The contralateral (left) breast also showed a similar but smaller mass at the 4 o’clock position in the middle ring of the breast. There were multiple enlarged lymph nodes with replaced hila in both axillae ( and ). One of the nodes in the right axilla showed foci of calcifications and measured 1.4 × 1.5 cm. An impression of bilateral breast masses was made and a final BI-RADS category of 5 (highly suggestive of malignancy) was assigned to the study.
She subsequently had ultrasound-guided CNBs performed on both breast masses and a histological diagnosis of bilateral IDC was made. The immunochemistry report was triple-negative. Fine needle aspiration was also performed on a palpable right supraclavicular lymph node and the histological report confirmed benign features.
Neoadjuvant chemotherapy was then offered while being worked up for bilateral mastectomy; she rejected both chemotherapy and surgery despite all the counsel given on the need and benefits of early intervention. She opted for alternative therapy owing to the lack of funds.
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pmc-6180831-1
|
We describe a case of a 40-year-old female nurse who presented in May 2003 with an 18-month history of pain in the left thumb. Clinical examination showed soft-tissue swelling around the left thumb metacarpal. Radiographs showed an expansile lesion occupying most of the metacarpal with periosteal reaction and cortical destruction. MR scan () showed extensive destruction with expansion of the shaft of the first metacarpal of the left hand, associated with a soft-tissue mass and an extraosseous component, primarily on the dorsal aspect. On T
1 weighted images, the lesion was of low signal; on fluid-sensitive sequences, the lesion showed high signal with a thin and irregular septae. Following contrast medium administration, inhomogeneous, multilobulated, peripheral enhancement of the lesion was noted but also areas of non-enhancement predominated centrally, consistent with a cartilaginous lesion.
The CT scan () demonstrated a lytic lesion involving virtually the entire shaft of the first metacarpal of the left hand and reaching the subchondral bone plate at both ends. The lesion demonstrated a significant expansion of the bone with small areas of punctuate calcification, significant thinning of the cortex circumferentially and a breach in the cortex with some new bone formation on the dorsal aspect. Some soft-tissue swelling was also seen. There was no evidence of pulmonary metastases on the CT scan () at initial diagnosis.
An open biopsy was performed in June 2003, the histology of which revealed a grade II chondrosarcoma with evidence of spread beyond the cortex into the periosteum. Vascular invasion was not identified. 1 month later, under general anaesthesia, a first ray amputation was performed with disarticulation of the thumb at the trapezioscaphoid joint. A tourniquet was used at the time of the surgery to exsanguinate the limb. Macroscopic examination revealed an expansion of the metacarpal bone due to a chondroid tumour measuring 35 × 25 mm, which eroded through the cortex but did not cross the metacarpophalangeal joint. Microscopic examination of the sections () confirmed a grade II chondrosarcoma, which showed an extensive permeative growth beyond the cortical bone. There was no de-differentiation and the tumour was contained within the periosteum. The lesion was completely excised, although the closest margin was 1 mm on the dorsal aspect.
In April 2004, the patient noticed a superficial, firm swelling in the medial aspect of the left upper arm, which was not particularly painful. There was no clinical or radiographic evidence of local recurrence in the hand. An MRI scan demonstrated a subcutaneous lesion () on the medial aspect above the elbow with signal characteristics similar to the previous chondrosarcoma in the ipsilateral hand. The mass was closely related and in the line of the cephalic vein; it showed high signal on the T
2 weighted images, intermediate signal on the T
1 weighted images and peripheral enhancement after intravenous gadolinium administration. Subsequently, an excisional biopsy of the left upper arm lesion was performed. Macroscopically, the soft-tissue mass showed encapsulated grey myxoid tissue, which was centrally cystic and partially haemorrhagic. This was microscopically confirmed to be a grade II chondrosarcoma, most likely representing a metastasis from the previous thumb chondrosarcoma. There was no lymphoid tissue seen that could be associated with the subcutaneous lesion to suggest lymph node metastases. The closest margin was less than 1 mm. At the same time, a biopsy of the hypertrophic scar at the site of ray amputation was performed, which did not reveal any evidence of neoplasia on histological examination. Owing to the close margins of this subcutaneous lump on excision, a wider excision was performed a month later under general anaesthesia.
In June 2004, a CT scan of the chest was performed and a solitary tiny nodule in the right middle lobe (), which was suspicious for lung metastasis, was seen. There was no mediastinal or hilar lymphadenopathy seen. The lesion continued to increase in size and the patient had a pulmonary lobectomy in November 2004. Within 2 months, however, she developed further lung metastases. In January 2005, she received palliative chemotherapy, but even after three cycles, the pulmonary lesions continued to increase in size and number () and it was decided to discontinue further treatment. The patient died subsequently from the disease.
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pmc-6180832-1
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A 31-year-old male presented to the orthopaedic clinic of our hospital with symptoms of right knee pain and joint instability. He experienced a feeling of the knee giving away while walking. He had no history of trauma. There was no tenderness or swelling of the knee on physical examination and the range of motion was normal. The patient displayed positive Lachman and anterior drawer test. He also had congenital ankle and foot deformities. He was later sent for an MRI of the right knee to look for any internal derangement.
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pmc-6180849-1
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A 54-year-old male patient presented to the emergency department complaining of fatigue and increasingly limited mobility in his right arm. According to his records, the patient had fallen 10 days previously and hit his head and right shoulder. Right-sided subcutaneous facial haematoma and a contusion mark on the right shoulder were observed during physical examination. The examination showed a moderately limited range of motion in the right shoulder. A CT scan of the head and an X-ray of the cervical spine and right shoulder were performed. The CT scan of the head and the X-ray of the cervical spine showed no signs of injury, and the X-ray of the right shoulder was interpreted as normal. Besides a history of smoking and excessive drinking, the medical history was unremarkable. Laboratory examination showed a slightly elevated C-reactive protein inflammatory marker (22 mg l–1), anaemia (red blood cell count = 3.02 × 1012 l–1, haemoglobin = 105 g l–1), thrombocytopenia (platelet count = 46 × 109 l–1), low haematocrit (31%) and an alcohol blood concentration of 55 mmol l–1. As no major injury was found, the patient was discharged. 2 weeks later, the patient returned to the emergency department complaining of fatigue, diffuse arthralgia and myalgia, with severe pain in his right shoulder. The skin on his right upper arm was swollen, reddened and painful to palpation, and his right axillary lymph nodes were enlarged. On examination, the patient had a pulse of 92 beats min–1, blood pressure of 68/38 mmHg, oxygen saturation of 97% and a temperature of 36°C. Laboratory examination showed an elevated C-reactive protein of 129 mg l–1, a white cell count of 11.6 × 109 l–1, red blood cell count of 2.09 × 1012 l–1, haemoglobin of 70 g l–1, a haematocrit of 21% and a gamma glutamyl transferase of 1.36 μkat l–1. The patient was hospitalized and diagnosed with right upper arm cellulitis and probable sepsis. An emergency ultrasound examination of the upper arm showed a collection of thick fluid with the presence of gas bubbles and a free fragment of the cortical bone (). At this point, the shoulder X-ray image that was taken during the patient’s first visit to the hospital was re-examined, and a clavicle fracture in the distal third of the clavicle was diagnosed (). In order to assess the anatomical relations between the collection of fluid and its adjacent structures and to better evaluate the extent of bone involvement, we immediately performed an MRI on a Signa scanner 1.5 T (General Electric Medical Systems, Milwaukee, WI). The imaging protocol was performed using a short tau inversion–recovery sequence (coronal plane), a T
2 fast relaxation fast spin-echo (FSE) fat-saturated sequence (axial plane) and a T
1 FSE sequence (coronal plane) before i.v. application of the paramagnetic contrast media, and afterwards with a T
1 FSE fat-saturated sequence (coronal, axial plane). The MRI confirmed osteomyelitis of the clavicle and moderate right-sided pleural effusion (). Apart from these MRI findings, the X-ray of the lungs also showed radiological signs of possible infiltration of the right lower lobe.
Empirical therapy began with 2 g 6 h–1 of i.v. floxacillin and, after Streptococcus pneumoniae and E. coli grew in the blood cultures, 2 g 6 h–1 of i.v. cefotaxime was added to the therapy. No bacteria were isolated from the right pleural punctuate and uroculture. A thorough physical examination revealed a deep 1 × 2 cm wound on the patient’s left fourth toe, exposing the underlying tendon. The wound showed no signs of infection, but polybacterial flora grew on the smear taken from the wound, in which the presence of E.coli was identified. The patient was not a suitable candidate for immediate operation owing to abnormal haemostasis (prothrombin time = 68.9 s; international normalized ratio= 2.45) and profound anaemia (treated with supportive therapy with three ampoules of phytomenadione intramuscular and six units of concentrated thrombocytes i.v.), until 2 days later, at which point surgical debridement and drainage were performed. A day prior to the surgery, there was a spontaneous discharge from the clavicle area of approximately 500 ml of pus. E. coli grew on a smear of the intraoperative right clavicular wound and a clavicle tissue sample.
Despite surgical treatment, the patient’s condition deteriorated rapidly during the next 48 h with the development of acute respiratory distress syndrome and cardiac arrest with asystole. After successful cardiopulmonary resuscitation and the return of spontaneous circulation, systemic inflammatory response syndrome developed with multiple organ failure. The patient’s condition deteriorated rapidly, and he passed away the following day.
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pmc-6180850-1
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A 22-year-old female presented with a 7-h history of sudden onset central abdominal pain. The pain was constant and unremitting, with associated nausea, followed by a few episodes of vomiting. She also reported reduced appetite. She denied any change in bowel habits and any urinary tract symptoms and had passed bowel motions with no difficulty earlier that day. She was previously well, with no previous medical problems or allergies. She was not a smoker and only drank alcohol occasionally. On admission, her pulse was 63 beats min–1 with a regular rhythm, temperature was 35.9 oC, blood pressure was 132/73 mmHg and her respiratory rate was 24 breaths min–1. On examination, she had a soft, non-distended abdomen with tenderness around her umbilical and suprapubic region. She also had fullness in her suprapubic region, thought to be a distended bladder. Initial blood tests showed normal liver and renal function (estimated glomerular filtration rate > 90) and C-reactive protein (< 3). She, however, had a low haemoglobin of 87.0 g dl–1, slightly low potassium of 3.3 mmol l–1, raised white cell count of 12.4 × 101 l–1 with a neutrophil count of 11.53 × 101 l–1 and a plasma lactate of 5 mmol l–1. Urine dipstick showed ketones +3 and blood +4 with no leukocytes or nitrites.
She was treated conservatively with i.v. fluids and potassium replacement, antiemetics and analgesia that she seemed to respond to. Following i.v. fluids, blood gas analysis showed a pH of 7.3, lactate of 2.12 and base excess of 2.5.
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pmc-6180852-1
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A 21-year-old female with primary ciliary dyskinesia and situs ambiguus was admitted electively for a diagnostic laparoscopy because of a history of recurrent subacute bowel obstructions. A pre-operative CT scan of her chest and abdomen showed that the heart was normally sited but the abdominal viscera were inverted. There was also polysplenia and absence of the suprarenal inferior vena cava (IVC). The infrarenal IVC was instead continuous with the azygos vein, with the resultant increased flow causing azygos dilatation. A further anatomical variant that was present was the azygos opening into the right lateral wall of the superior vena cava (SVC) instead of its usual drainage into the posterior wall.
Intraoperatively, extensive jejunal adhesions were found, which required conversion from a laparoscopic to an open procedure. Adhesiolysis and appendicectomy were performed. In the early post-operative period, the patient had a prolonged ileus with intractable vomiting and high nasogastric tube output. As she was unable to tolerate oral nutrition, it was decided to start her on total parenteral nutrition (TPN), for which a peripherally inserted central venous catheter (PICC) insertion was requested.
The PICC was inserted under fluoroscopic guidance using a modified Seldinger technique by a radiology registrar and consultant interventional radiologist. The left arm was abducted to 90° during insertion and venous access was obtained via the left basilic vein. During the procedure, there was difficulty advancing the nitinol guidewire into the SVC. A digital subtraction angiogram was performed that demonstrated thrombus in the left brachiocephalic vein (). The nitinol guidewire was exchanged for a 0.018” Terumo Radifocus® guidewire (Terumo, Tokyo, Japan) that passed through the thrombus without difficulty into the SVC. A 5 French Cook Turbo-Ject® (Cook Medical, Bloomington, IN) double-lumen polyurethane PICC was then inserted over the guidewire with its tip sited in the distal SVC (). Blood was readily aspirated from the PICC and the line was flushed and secured. To prevent excessive catheter length outside the patient, the distal portion of the PICC was cut before insertion.
TPN was commenced the same day at a rate of 1.5–2.5 l day–1, and a left internal jugular vein (IJV) line that had been in situ was removed. Over the following week, the patient’s ileus gradually resolved. On the ninth day following PICC insertion, the patient experienced dyspnoea and pleuritic chest pain. A chest radiograph was performed () that showed a small right-sided pleural effusion. A curve at the distal end of the PICC was also noted, which was reported as coiling of the PICC within the SVC. TPN infusion was continued because the PICC could still be aspirated and flushed.
Over the next 24 h, the patient deteriorated further and became tachycardic, tachypnoeic and hypoxic. A repeat chest radiograph was obtained that showed large bilateral pleural effusions (). The PICC remained in the same position as the previous day. A CT pulmonary angiogram (CTPA) was requested to exclude a pulmonary embolus (PE) and look for a cause for the rapidly increasing pleural effusions.
The CTPA was negative for a PE but did demonstrate large bilateral pleural effusions, a moderate-sized pericardial effusion, a mediastinal effusion and pneumomediastinum (). The PICC was again reported as being coiled within the SVC and repositioning was advised.
An echocardiogram performed to assess the pericardial effusion showed no evidence of tamponade. In view of the large bilateral pleural effusions, a pleural aspiration was performed. Milky white fluid was obtained, similar in appearance to TPN solution. There was no blood in the aspirate. Biochemical analysis confirmed that the aspirated fluid was TPN solution and not chyle. This raised the suspicion of vascular perforation by the PICC.
The patient was transferred to a cardiothoracic centre and bilateral intercostal chest drains were inserted. A total of 2 l of TPN solution was removed. A repeat CT scan showed that the PICC was not actually coiled within the SVC, but had migrated to the azygos and caused a perforation (). The cardiothoracic surgeons decided to remove the PICC with close observation afterwards for any signs of deterioration. The patient remained clinically stable and made a good recovery. She was discharged home a week after removal of the PICC.
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pmc-6180853-1
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A 12-year-old female child presented to the gynaecology outpatient department with complaints of continuous dribbling of urine for the past 6 months. She had not attained menarche and had a history of fall and pelvic injury 3 years back. Her general physical examination was unremarkable. On local examination of the external genitalia, there was marked excoriation of the perineal and vulval skin. Foul smelling urine was observed coming out of the vaginal opening. Her routine laboratory investigations such as haemoglobin, total leukocyte count, differential leukocyte count, erythrocyte sedimentation rate, blood urea and creatinine were within normal limits. Based on the history and clinical examination, a provisional clinical diagnosis of post-traumatic vesicovaginal fistula (VVF) was made and the patient was referred to the radiology department for ultrasonography (USG) of the kidneys, ureters and bladder.
USG was performed on a GE Logiq P5 machine (General Electronics Co., Milwaukee, WI) and revealed mild bilateral hydronephrosis. A curved echogenic focus with posterior acoustic shadow was seen within the lumen of the partially distended urinary bladder measuring approximately 25 mm in size, suggestive of a vesical calculus (single arrow in ). Another echogenic shadow was seen between the urinary bladder and the rectum, raising suspicion of a vaginal foreign body (double arrow in ). When enquired, the patient and her parents denied the insertion of any foreign body into the vagina. The child was taken for an urgent non-contrast CT scan of the pelvis for confirmation of the USG findings. The CT was performed on a Philips Brilliance 16 machine (Phillips Healthcare, Amsterdam, Netherlands), which revealed a calculus of size 28 × 25 × 18 mm in the lumen of the urinary bladder (horizontal arrows in and ). A big rectangular calcified mass was seen in the vagina measuring 53 × 29 × 33 mm in size (vertical arrows in and ). A well-defined rectangular hypodense rim was noted inside the calcified mass measuring 36 × 18 mm in size (arrowheads in and ), containing an air dense area in the centre. The patient was again asked about the vaginal foreign body and she admitted to inserting the plastic cap of a nail colour into her vagina about a year back.
An MRI of the pelvic organs was performed the next day on a 1.5 T GE Signa Excite (General Electronics Co.) for detailed evaluation. The following sequences were employed: sagittal T
2 weighted fast spin echo (FSE) [repetition time (TR) 4243 ms, echo time (TE) 63 ms]; sagittal T
2 weighted fat-saturated (FS) FSE (TR 4600 ms, TE 63.3 ms); sagittal T
1 weighted FSE (TR 500 ms, TE 8 ms); coronal T
2 weighted FS-FSE (TR 4600 ms, TE 63.3 ms); coronal T
2 weighted FSE (TR 4200 ms, TE 63.3 ms); coronal T
1 weighted FSE (TR 520 ms, TE 8 ms); axial T
2 weighted FSE (TR 5020 ms, TE 106.2 ms); axial short tau inversion-recovery (TR 6260 ms, TE 55.8 ms, inversion time 150 ms); axial T
1 weighted FSE (TR 440 ms, TE 9.1 ms); axial post-intravenous gadolinium T
1 weighted FS-FSE (TR 900 ms, TE 9.1 ms); coronal T
1 weighted FS-FSE (TR 760 ms, TE 7.9 ms); sagittal T
1 weighted FS-FSE (TR 720 ms, TE 8.7 ms). A big vaginolith measuring 52 × 28 × 35 mm in size was seen in the vagina, which was hypointense on all pulse sequences (multiple small arrows in and ). A well-defined rectangular rim of intermediate signal intensity was seen inside the hypointense mass, suggesting the presence of a foreign body (double arrows in and ). A defect measuring approximately 6 × 5 mm in size was observed in the posterior wall of the urinary bladder, with free passage of urine into the vagina (single arrows in and ). A well-defined T
1 and T
2 weighted hypointense calculus was seen in the lumen of the partially distended urinary bladder (23 × 16 × 25 mm).
Based on the radiological findings and history, a diagnosis of vaginal foreign body with secondary vaginolith with vesical calculus with VVF was made. The patient was given antibiotic cover. The vaginal foreign body and the vesical calculus were removed via a suprapubic approach under general anaesthesia. The VVF was repaired by suturing the vaginal and bladder wall defect. The patient had an uneventful postoperative stay. The child is healthy and asymptomatic after 3-month follow-up.
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pmc-6180854-1
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A 25-day-old term baby female presented with neonatal jaundice and hyperbilirubinemia. A biliary cyst and a contracted gallbladder were diagnosed in a post-natal ultrasound from another institution. She was transferred to our hospital at day 19 of life. A repeat ultrasound showed a small gallbladder (length 1.7 cm; diameter 0.3 cm) connected to an extrahepatic cystic structure, which measured 1.4 × 0.6 cm (). The content of the cyst was anechoic and there was no dilatation of intrahepatic bile ducts. A hepatobiliary iminodiacetic acid scan on day 26 of life showed no biliary drainage up to 28 h. A PTTC on day 35 of life showed there was prompt opacification of the known extrahepatic cyst, followed by visualization of a small gallbladder. There was no passage of contrast into bile ducts or the duodenum. Aiming to demonstrate that there was no communication of this cyst with the biliary system as well as to mechanically remove any source of obstruction, the contrast injection was sustained until there was an extraperitoneal perforation of the cyst () (radiation dose: 1.1 mGy). The rationale to sustain the injection was to demonstrate a connection of the cyst with the biliary tree and our experience that there may be a benefit of mechanical lavage of the biliary tract in cases of obstruction by secretions or sludge, which has been reported by our institution in neonates with parenteral nutrition-related cholestasis. An uncomplicated ultrasound-guided biopsy was performed. Intravenous antibiotics were started owing to perforation of the cyst and the patient recovered well from the procedures. The biopsy result was consistent with extrahepatic biliary obstruction.
At the time of surgery, a cystic structure, distinct from the gallbladder, was encountered, which was located in the common bile duct. Proximally, the cyst was in continuity with a cord-like hepatic duct. A standard Kasaï procedure was performed with a hepaticojejunostomy. Subsequently, the patient’s jaundice resolved.
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pmc-6180854-2
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A 51-day-old term baby male presented with neonatal jaundice, hyperbilirubinemia and abnormal liver function tests. Ultrasound showed a cystic structure anterior to the portal vein measuring 2.3 × 1.6 × 1.8 cm. The gallbladder had an unusual, small, irregular appearance measuring 3.9 cm in length and 0.6 cm in diameter (). There was no sludge in the cyst and no intrahepatic bile duct dilatation. A PTTC on day 56 of life showed opacification of a small gallbladder connected to a prominent cystic structure (). No passage of contrast into the bile ducts or the duodenum was observed. To definitively exclude a connection of the cyst, the contrast injection was maintained until there was an extraperitoneal perforation of the cyst () (radiation dose: 2.3 mGy). An uneventful ultrasound-guided biopsy was then performed. Intravenous antibiotics were started and the patient recovered well from the procedure. The biopsy result was consistent with large duct obstruction, with early signs of liver fibrosis.
Dissection of the porta hepatis at the time of surgery revealed cystic dilatation of the common bile duct without communication to the duodenum and a fibrotic hepatic duct proximally. This was resected at the level of the portal plate and a Kasai hepaticojejunostomy was performed. The child’s jaundice resolved postoperatively.
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pmc-6180855-1
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A 70-year-old male was referred to our hospital complaining of left flank pain. At physical examination, nothing relevant was observed and laboratory findings were within normal limits. A CT examination of the abdomen and the pelvis was performed with a multidetector scanner, before and after contrast media administration. Portal phase images showed a large amount of solid tissue in the left perirenal space, infiltrating the renal capsule and the main renal vessels; the tissue did not show significant contrast enhancement. Similar findings were detected also in the right perirenal space (). CT images also revealed a partial stenosis of the common bile duct, with intrahepatic bile duct ectasia owing to hypervascular eccentric tissue (). Hence, a diagnostic integration with endoscopic retrograde cholangiopancreatography was performed to exclude an intraductal proliferation. A biopsy was also performed in the left perirenal space; the pathological samples were composed of connective and adipose tissues, revealing the histological features of a DT or abdominal fibromatosis and also showing immunohistochemical markers typical of muscular tissues, such as actine. The tumour was considered unresectable and medical therapy was started with tamoxifen (20 mg die–1); after an episode of thrombophlebitis, the patient asked to suspend tamoxifen and accepted a new therapeutic regimen (docetaxel 75 mg m−2 every 3 weeks); unfortunately, even this treatment was discontinued after only 4 weeks owing to neuropathy. A new CT examination was then performed to assess the results of the treatment. Unexpectedly, on venous phase images, the perirenal tissue showed a remarkable reduction on the left side and had almost disappeared on the right side (). The peribiliary tissue had equally decreased in size and thickness (). The treatment was then discontinued in accordance with the patient’s decision. 1 year later, both the left perirenal and peribiliary tissues demonstrated no progression and remained clinically stable on off-treatment; however, new tissue was visible surrounding the right renal pelvis and the calices (). The same therapeutic regimens (tamoxifen and docetaxel) were proposed to the patient based on the previous good response; unfortunately, the patient refused any treatment.
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pmc-6180856-1
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A 65-year-old male was referred to our hospital. He had presented to another hospital 6 months earlier with drowsiness and a 54-mm diameter mass had been observed in the right temporal lobe on non-contrast CT scan. The patient had undergone surgery and cobalt-60-based external beam radiotherapy for pituitary adenoma 43 years ago. Parallel–opposed lateral radiotherapy targeting the pituitary lesion was employed with a total dose of 50 Gy in 25 fractions. The patient had recovered without residual symptoms but required hormone replacement for panhypopituitarism. He had also developed pontine infarction at 57 years of age. The results of physical and neurological examinations at the time of admission were normal. Laboratory evaluations of complete and differential blood counts, and serum chemistry were also normal.
The patient underwent a contrast-enhanced brain MRI that revealed a well-demarcated mass in the right temporal lobe (). A mass consisting of hyper- and hypo-intensities was observed on T
2 weighted imaging. There was extensive vasogenic oedema around the mass. The T
1 weighted image showed a hypointense mass with hyperintense areas in the periphery, suggesting haemorrhagic foci. Contrast-enhanced T
1 weighted image of the brain showed significant contrast enhancement in the hypointense area on the pre-enhanced T
1 weighted image. The mass was supplied by the inferior branch of the right middle cerebral artery, and conventional angiography showed spotty stains in the arterial phase and spreading and pooling of the contrast medium in the venous phase, which suggested the presence of blood sinus-like structure in the mass (). CT images of the chest, abdomen and pelvis were normal (data not shown). Because hyperintense areas in the bilateral temporal lobes, indicating radiation-induced changes, had been detected on the T
2 weighted image 1 year before (), the mass was considered to arise within the radiation field of the previous radiotherapy, which probably involved opposing portal irradiation. The preoperative diagnosis was radiation-induced lesions, including cavernous malformation and glioma. Surgical resection of the mass was performed and it was found to be highly haemorrhagic and richly vascularized. The mass and the hippocampus were resected because the mass bled easily and had invaded the hippocampus.
Pathologically, the mass exhibited widespread haemorrhages and abnormal vessel proliferation. The abnormal vessels contained organized blood clots, and had thick and hyalinized walls. The dilated intravascular lumens were covered by epithelial cells that were immunohistochemically positive for CD34. These cells exhibited variable cytologic atypia and mitotic activity (1–2 per 10 high power field) (). These pathological findings were consistent with that of an angiosarcoma of the brain.
Complete surgical resection was achieved and no residual tumour was evident on the postoperative MRI (). No surgical complications occurred. Although the patient experienced more drowsiness than before, and lost his appetite after the operation, he gradually recovered and was discharged. On the basis of the histopathological diagnosis, three-dimensional conformal radiation therapy with a dose of 61.2 Gy in 34 fractions and chemotherapy with temozolomide were administered. At the 9-month follow-up, the MRI revealed multiple vertebral metastases. The patient died 13 months after the surgery.
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pmc-6180858-1
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A 31-year-old female of Indian descent originally presented with chronic right-sided nasal obstruction, congestion and sinusitis. She previously underwent septoplasty and endoscopic sinus surgery 8 years ago. Her symptoms persisted and the deformity of her nasal bridge became more splayed, taking on the appearance of an external nasal mass. A biopsy revealed rich inflammatory infiltrate surrounding the blood vessels with a prominent onion-skin pattern, consistent with EAF extension into bony and skeletal muscle tissue ().
A tertiary referral was then made to our department 3 years ago. Her main complaints were severe nasal blockage and sinus pain, but no epistaxis. The patient was otherwise in good health with no signs of systemic vasculitis or autoimmune disorder and she was not on any medication. There was no significant smoking or alcohol history. She had an allergy to penicillin. The patient had immigrated from India at the age of 16 years.
Physical examination revealed involvement of the nasal bones and cartilage, resulting in an enlargement and expansion of the nose. There was significant right-sided nasal passage obstruction with a soft tissue mass that had an oedematous appearance.
MRI showed a lobulated diffuse soft tissue mass of the nasolabial folds bilaterally, extending posteriorly to involve the anterior half of the inferior and middle turbinates as well as the anteroinferior nasal septum, mildly narrowing both nasal vestibules (). There was soft tissue thickening extending to the nasal bridge.
Given the functional and cosmetic difficulties of gross total removal, the patient underwent subtotal resection, including removal of the nasal bones through an open septorhinoplasty approach. The resultant defect was reconstructed with rib grafts. The post-operative recovery was uneventful and the patient’s symptoms had improved. The pathology report confirmed EAF. 4 months postoperatively, the follow-up MRI documented residual disease along the right nasofacial groove with mild mass effect. Subsequent MRIs over 2 years of follow-up showed minimal progression. The patient continued to complain of mild but stable right nasal obstruction. A radiation oncology opinion was obtained and the patient was presented at the institutional tumour board. The consensus of opinion was that the risks associated with additional surgery, radiation or immunosuppressive therapy outweighed the potential benefits. In the absence of severe symptoms and no evidence of disease progression, the recommendation was for continued observation. The patient is being monitored and further treatment will be reconsidered should there be progression.
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pmc-6180858-2
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A 58-year-old male presented with a palpable mass in the anterior nasal septum that had been gradually increasing in size over 1 year. His symptoms included bilateral nasal obstruction and persistent rhinorrhoea. There was no history of epistaxis, significant medical issues, medications or allergies. He had an 18 pack-year smoking history.
On examination, the nasal septum was expanded anteriorly with a firm submucosal mass obstructing an estimated 50% of each nasal airway. MRI showed the anterior septal mass extending into the pre-maxillary space with partial erosion of the hard palate ().
Biopsy of the nasal mass revealed extensive perivascular fibrosis in an “onion-skin” pattern, as well as mixed inflammatory infiltrate, including eosinophils, few plasma cells and lymphocytes, consistent with EAF ().
Total resection of the mass would have required removal of the caudal septum, anterior nasal spine and areas of hard palate, which would be difficult to reconstruct. Given the minor nature of his symptoms and no significant nasal stenosis or mass deformity, observation was recommended. Subtotal resection will be considered if the patient progresses.
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pmc-6180859-1
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A 50-year-old male presented with complaints of chronic, intermittent abdominal pain. The patient had a 20-year history of mild-to-moderate amount of alcohol consumption. There was no history of jaundice, fever or weight loss. His laboratory tests revealed no significant abnormal findings. Serum amylase and lipase, and tumour markers [CA 19-9, carcinoembryonic antigen (CEA)] were within normal limits. The patient was subjected to a CT examination. On unenhanced CT image, a poorly defined soft tissue mass was seen in the pancreaticoduodenal (PD) groove with a hypodense cystic lesion within the mass (). On post-contrast study, the lesion showed minimal enhancement in the portal venous phase ( and ), but delayed imaging at 2–3 min showed mild persistent enhancement of the lesion compared with the pancreatic parenchyma that was consistent with scar tissue () and a non-enhancing cystic lesion within the lesion. The lesion showed poorly defined fat planes with the adjacent second part of the duodenum on its right side and pancreatic head on the left side. Mild thickening of the wall of the second part of the duodenum adjacent to the lesion with variable luminal narrowing was noted. The common bile and pancreatic ducts appeared grossly normal. The pancreatic body and tail were normal. In order to clearly delineate the ductal system and the periampullary region, and to know the extension of the lesion, the patient was also subjected to an MRI examination. Axial two-dimensional fast imaging employing steady-state acquisition () sequences showed soft tissue signal intensity lesion in the PD groove with a cystic lesion within the lesion and the aforementioned CT scan findings. MR cholangiopancreatography sequence () revealed smooth and regular tapering of the pancreatic and common bile ducts. The gallbladder was distended and the cystic duct was normal. Incidentally, a few simple cysts (Bosniak 1) were noted in both the kidneys. The patient was advised further surgical intervention but he refused and was managed with conservative treatment. At present, the patient is asymptomatic.
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pmc-6180863-1
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DC, a 51-year-old male, underwent complete resection of a tracheal lesion in 1981. The lesion was 9 cm below the vocal cords and 4.5 cm superior to the carina. It measured 4.5 cm in length, and a total specimen length of 7 cm was resected (allowing for margins) via midline sternotomy, followed by end-to-end anastomosis. Histology demonstrated an ACC. He did not undergo adjuvant therapy.
In March 2011, DC presented with symptoms of a lower respiratory tract infection. Investigations, including CT/MRI of the thorax, demonstrated a mass in the trachea ( and ). Bronchoscopy demonstrated a smooth, lobulated lesion on the right posterolateral wall of the trachea with a 25% cross-sectional encroachment of the trachea. Biopsy and histology confirmed local recurrence of ACC. A positron emission tomography/CT (PET/CT) scan showed low-grade avidity in the tumour area with no evidence of metastatic disease.
After extensive multidisciplinary discussion and wide surgical consultation, the lesion was considered unresectable and therefore the patient was considered for primary radiation therapy. In light of the histology, it was felt that the best radiotherapy approach would be with FNT and so DC received a standard curative dose of 20.4 Gy in 15 daily fractions given three fractions per week from November until December 2011. The relative biological effect (RBE) of neutrons is dependent on the way they are produced. At iThemba LABS (Cape Town, South Africa), where the patient was treated, an RBE of 3 for normal tissue has been used for all treatments given on the p(66)/Be isocentric unit. Hence the equivalent photon dose to the normal tissue was 61.2 Gy. For the dose plan, the gross tumour volume (GTV) was delineated and the clinical target volume (CTV) included circumference of the trachea combined with a 5-mm margin around the GTV. The planning target volume (PTV) was obtained by expanding the CTV by 5 mm in all directions ().
Follow-up consisted of regular clinical examinations and 6-monthly MRIs for the first year, and subsequent yearly MRIs. He also underwent an oesophagogastroduodenoscopy in 2014, which was normal. These serial MRIs showed a gradual disease response with reduction in the size of the ACC ( and ). This response to neutron therapy is characteristic for this pathology. Clinically, the patient is doing very well and is not reporting any late side effects of the treatment.
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pmc-6180864-1
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A 69-year-old female patient was diagnosed with advanced cervical carcinoma Stage IIIb. She had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy, as well as completed 36 cycles of radiochemotherapy. A restaging CT scan showed a new solitary segment VIII liver metastasis measuring 3.1 (width) × 3.1 (AP) cm ().
In view of the solitary liver metastasis, an RFA was performed. Using the right intercostal approach, an internally cooled 15-cm single electrode with a 3 cm active tip (Cool-tip™, Valleylab, Boulder, CO) was inserted into the tumour’s epicentre under ultrasound guidance. No repositioning of the radiofrequency needle was carried out. Ablation was performed for approximately 12 min. No immediate complication was encountered and the patient was discharged the next day.
A CT scan of the abdomen in the portal venous phase was performed 6 weeks after the ablation. There was residual tumour circumferentially. An intensely enhancing area [measuring 2.3 cm (width) × 1.4 cm (AP)] was noted within the inferolateral aspect of the ablated lesion. The degree of enhancement of the lesion was similar to portal and hepatic veins (). No demonstrable communication with the intrahepatic vessels was noted. Based on the CT scan findings, it was thought that the pseudoaneurysm likely originated from the portal or the hepatic vein. However, the single-contrast phase of the CT images made it difficult to identify the origin of the pseudoaneurysm. Extrahepatic disease progression was noted on follow-up CT scan, as evidenced by the enlarged para-aortic nodes and the peritoneal deposit at the splenic hilum. The patient was treated conservatively as she was asymptomatic and not keen on further intervention.
A CT scan of the abdomen 12 weeks after the ablation revealed progression of the segment VIII liver metastasis. The intensely enhancing area was no longer seen, indicating spontaneous resolution of the pseudoaneurysm. There was also progression of other intra-abdominal metastatic disease.
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pmc-6180866-1
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A 76-year-old Caucasian, non-smoking female suffered a minor stroke in August 2014 owing to hyperthyroidism-induced atrial fibrillation that was later diagnosed as Graves’ disease. She was initially prescribed carbimazole 10 mg to stabilize the disease, which was then increased to 20 mg in January 2015. Thyroxine 25 mcg was initially given to normalize free T4 hormone and hyroid-stimulating hormone, which was then increased to 100 mcg in August 2015.
She presented with bilateral upper lid oedema, watery eyes and conjunctival injection in September 2014. This progressed to periorbital but painless oedema and transient diplopia over 6 months. Selenium 200 mcg was also recommended, as it has shown some efficacy in mild TED. She was given Hypromellose, Viscotears®, and Lacri-Lube® to maintain moisture and comfort. In March 2015, she regressed with monochromatic vision in her left eye, faded vision in both eyes, significant bilateral proptosis and restricted eye movement. A CT scan of the orbits with intravenous (IV) contrast showed enlarged extraocular muscles in both eyes with possible compression of the left optic nerve (). She began steroid therapy with IV methylprednisolone: 500 mg three times for the first week, 250 mg per week for the next 6 weeks and then tapering oral prednisolone starting at 60 mg. She was given alendronic acid to prevent worsening of her osteoarthritis and was also started on omazeprole. There was improvement in left optic nerve function and reduced oedema.
She commenced OR in May 2015. She was given 20 Gy in 10 fractions over 2 weeks with 6 MV photons, using lateral opposing beams while avoiding the lenses. A Perspex® shell immobilized the head and neck. shows the treatment plan and dose volume histogram. She experienced increased inflammation and erythema of the eyelids after the first three treatments, which was managed with steroids and eye drops.
A follow-up in May showed her to be euthyroid with free T4 of 12.6 and her condition was active but stable. She showed overall improvement in visual acuity in both eyes and colour vision in her left eye a month after OR. Another follow-up in August 2015 showed no signs of optic neuropathy, reduction in upper lid oedema, normal pupillary reactions and normal conjunctivae. Her condition was deemed inactive in October 2015, although with some lingering strabismus. This will be corrected by surgery if the disease remains stable after 4 months.
TED affects females five times more than males, and smokers have a five- to seven-fold increased risk. Thyrotropin-sensitive immunoglobins bind to thyrotropin receptors in periorbital tissue, causing an inflammatory response that includes invasion of T-lymphocytes and macrophages. This creates fibroblasts between muscle fibres and orbital fat that become oedematous, with local cytokines magnifying the inflammatory response. Radiotherapy is effective in suppressing inflammation and inhibiting lymphocyte infiltration. The natural history of TED can vary widely from spontaneous remission to increasing severity, with three phases (active, inactive and burnout) determined by a clinical activity score (CAS). OR is reserved for active disease; inactive disease management includes symptom alleviation using artificial tears, sunglasses or prisms. Orbital decompression to relieve proptosis, muscle corrective surgery for recti muscles and eyelid oculoplastic surgery can be performed once the condition becomes inactive. Somatostatin analogues are another systemic option that could be used in combination with steroids. TED is difficult to treat because of the variability of symptoms expressed, length of disease phases, and factors such as thyroid status and smoking, which may alter its natural history.
Radiotherapy remains controversial owing to inconsistent results from previous trials, especially with proptosis and diplopia. There is also a lack of data on the effectiveness of OR with corticosteroids, as most prospective studies are OR vs sham irradiation or corticosteroids. An OR vs sham study only showed significant changes in motility (82% OR vs 27% sham) in moderate and severe cases, without significant improvements in proptosis or eye swelling. However, another study showed an improvement in proptosis (52% vs 27%) for mild cases. These results could have been confounded by treating mild TED at its inactive phase, which would underestimate its therapeutic ability. Additionally, the two trials grouped outcome measures into “major” and “minor” changes, which may also over- or underestimate the improvement of each symptom. Marquez et al utilized post-OR patient questionnaires after 1 year and ophthalmologic evaluations scored by SPECS (periobital soft tissue changes, proptosis, extraocular muscle dysfunction, corneal abnormalities and sight changes) to evaluate efficacy. 84% of patients responded with an improvement in symptoms, and 89% of SPECS scores were lowered. Almost all studies agree that OR is effective in treating visual acuity and optic nerve compression. Hahn et al have shown combination therapy to be effective, improving diplopia (31%), proptosis (2.5 mm left and 2.0 mm right), visual acuity (81%) and extraocular movement (58%). OR was evaluated retrospectively by the ability to taper from corticosteroids: 90.9% of patients were off it within 6 months without further exacerbation.
Variations in treatment delivery [energy, beam design, source-axis distance (SAD) and fractionation] may have affected treatment results. One study involved irradiation of one eye using a wedge pair and sham with the contralateral over 6 months and vice versa. However, the sham-irradiated eye received a dose of 2 Gy, which was enough to cause therapeutic changes. Angling beams posteriorly to avoid the lenses compared with half-beam blocking could affect dose distribution. Recently, several studies on using advanced radiotherapy modalities such as intensity modulated radiation therapy and tomotherapy have shown better dose uniformity and sparing to normal tissues. Almost all studies used isocentric positioning except for one that had a SAD of 128.3 cm. 20 Gy in 10 fractions was most widely used in the literature reviewed, although other fractionation schemes (1 Gy per week for 10 or 20 weeks) have shown clinically significant therapeutic responses. Almost all studies agree on the tolerability and safety of OR, showing no increase in secondary malignancies and difference in survival. Marcocci et al showed cataract formation in 12% of patients with a median of 11 years after treatment and a median age of 59 years.
OR with corticosteroids has been shown to be effective and tolerable, improving our patient’s visual acuity and colour vision, and reducing upper lid oedema. Our patient benefited from active monitoring that led to quick intervention during its active phase. However, she may require further intervention after an extended period of disease inactivity. Prospective studies of OR and steroid combination therapy with consistent parameters (CAS score and ocular symptoms) and patient eligibility (disease activity and smoking status) are needed to provide proper analyses of its effectiveness.
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pmc-6180867-1
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A 20-year-old female presented to the emergency department with a 5-day history of fever, pain and lump in the right hypochondrium. The laboratory examination was unremarkable except for mild leukocytosis. This was followed by an ultrasound examination that revealed a well-defined, round-to-oval, heteroechoic, part solid and part cystic lesion with internal vascularity in the subhepatic region, with loss of planes with the anterior abdominal wall muscles. The mass was seen separately from the gallbladder, which showed multiple intraluminal calculi with normal wall thickness. No other significant finding was seen in the abdomen. This was followed by a contrast-enhanced CT scan of the abdomen that revealed a large (approximately 7 × 6 cm sized) solid cystic mass lesion in the right subhepatic region showing intensely enhancing solid areas with peripheral cystic non-enhancing areas (,). The mass showed loss of fat planes, with focal infiltration of the adjacent anterior abdominal wall muscles. Arterial supply to the mass was from a branch of the right gastroepiploic artery, while venous drainage was via the superior mesenteric vein through the right gastroepiploic vein (). Owing to its drainage into the omental veins (“omental vascular pedicle sign”), the origin of the mass was ascertained to be from the greater omentum. Loss of fat planes with the anterior abdominal wall muscles suggested a possible malignant aetiology. Based on the imaging findings, a primary diagnosis of malignant omental mass was suggested. The patient was operated on and underwent wide local excision. Intraoperative appearance confirmed the omental origin of the mass with other findings being similar to those suggested by the CT scan. Gross pathological examination showed a fleshy mass with white tan surface and areas of haemorrhage measuring approximately 7 × 6 cm. Histopathological examination of the mass showed the typical appearance of alternating hypercellular and hypocellular areas, with cells arranged in a fascicular pattern within the hypercellular areas. Immunohistochemistry of the tumour cells showed positive staining for S100 and negative results for α-smooth muscle actin, desmin, c-kit, and cluster of differentiation 34, which was suggestive of a MPNST. The margins of the resected specimen were negative on microscopic examination. As the patient belonged to the reproductive age group, she was kept under regular follow-up. and after a short period of 6 months, she developed local recurrence in the abdominal wall. The patient subsequently underwent chemoradiotherapy and is on follow-up.
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pmc-6180874-1
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A 73-year-old male was referred to the spinal team with a presentation of becoming “off legs” with progressive difficulty in walking. He had a prior history of vertebral PD, diagnosed 11 years ago, but had reported no symptoms of back pain in the interim.
In the recent months, he had started developing paraesthesia in both lower limbs, with progressive leg weakness and difficulty walking.
There was no bowel or bladder involvement. His past medical history included chronic kidney disease, Type II diabetes mellitus and vitamin D deficiency. He was also noted to be human leukocyte antigen B27 positive.
Clinical examination revealed a rigid thoracic kyphosis and spastic paraparesis. Lower limb power was globally reduced to Medical Research Council grade 4/5. Altered sensation to fine touch was demonstrated below the level of T7.
Subsequent investigations included whole-spine MRI and CT. This demonstrated the features of AS with multilevel syndesmophytes and interspinous ligament calcification. There was cortical thickening, sclerosis and vertebral squaring of T10, consistent with the known history of PD. However, in addition, there was contiguous spread of the pagetic changes across the diffusely ankylosed thoracic segments (). The combination of these pathologies produced a marked kyphotic deformity, with extensive bony expansion of the pagetic thoracic spine that resulted in significant central canal stenosis ().
An MRI confirmed the extent of canal stenosis and cord compromise, with intramedullary T2 hyperintensity extending from the cervicothoracic junction to T11 (). There was sparing of the lumbar segments, with a normal appearance of the distal cord and conus ().
Following discussion at our regional spinal multidisciplinary team, it was decided that surgical decompression would likely result in poor outcome, given the extent and severity of the disease. Multiple infusions of zoledronate were administered, in addition to three courses of calcitonin, in an attempt to delay the progression of the disease. Despite this medical therapy, the patient continued to suffer from progressive myelopathy.
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pmc-6180877-1
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A 10-year-old female was admitted to our department with a grade 3/6 continuous murmur on the right side of the chest. When she was 2 years old, a cardiac murmur was incidentally detected during a routine clinical examination. Echocardiography performed at the local hospital at that time showed CAF. However, the local doctor decided not to perform surgery considering her very young age and weak physical condition. During annual follow-up via transthoracic echocardiography, the fistula did not show spontaneous regression, although the patient was asymptomatic with a normal exercise capacity. On clinical examination, no other significant abnormality was noted.
A two-dimensional transthoracic echocardiography performed after admission revealed the abnormal vessel and the shunt rate of the fistula ostium (systolic period: 5.4 ms–1 and diastolic period: 3.5 ms–1), but normal ejection fraction (EF; 67%; ).
The CTCA (dual-source CT, SOMATOM Definition Flash; Siemens Medical Systems, Berlin, Germany) revealed particularly well the giant and tortuous vascular structure, located posterior to the root of the aorta and anterior to the left atrium (LA). The fistula had an overall length and width of over 7.7 and 2.0 cm, respectively; the maximum LMCA and SVC width were 1.3 and 4.2 cm, respectively. No apparent abnormality was seen at the origin and along the route of the left anterior descending, left circumflex and RCA ().
Following her doctor’s advice, the patient underwent on-pump surgical repair. During the operation, a fremitus of SVC could be felt and the fistula’s ostium in the SVC, approximately 4 mm, was sutured. 7 days later, an echocardiography was re-examined and showed no abnormal blood flow between the LMCA and the SVC (). The patient was discharged from the hospital in good condition.
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pmc-6180878-1
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An 81-year-old female presented to our tertiary referral centre with non-specific epigastric pain of increasing severity and frequency. Comorbidities were limited to hypertension. The presence of a 67-mm infrarenal AAA extending distally to the aortic bifurcation was confirmed on CT angiography (). The aneurysm sac contained no intraluminal thrombus. The neck, however, was extremely angulated with the proximal landing zone measuring 16 mm in diameter. The right common iliac artery was ectatic and measured 16 mm, with the left being of normal calibre and appearance. Both external iliac arteries were found to be tortuous but within normal limits in diameter and measured 7.8 and 7.6 mm on the right and left side, respectively. A stress echocardiogram showed good left ventricular function. Pulmonary function was satisfactory with a forced vital capacity of 125% of predicted and forced expiratory volume in 1 s/forced vital capacity ratio of 84%.
Given the patient’s age and general condition, the surgeon’s assessment stated that open surgery would carry a significant risk of morbidity and mortality. Therefore, EVAR was thought to be the preferred treatment modality, reflecting the advantages of minimally invasive surgery and the patient’s preference over open repair. The significantly narrowed aneurysm neck precluded the use of standard endografts. “Off-the-shelf” abdominal aorta devices have a minimum diameter of 23 mm. For our patient, this entailed 43% oversizing of the native aorta. To overcome the challenging anatomical morphology, we considered a novel endovascular option of deploying a small diameter and short thoracic endograft into the proximal neck of the aneurysm combined with telescopic deployment of a branched iliac device. Consensus was gained to proceed with this approach following discussion at our local multidisciplinary team meeting.
Intraoperatively, the patient was positioned supine and adequately prepped. Surgical access was obtained via bilateral groin cut-downs. Following systemic heparinization (5000 units), a pigtail catheter was introduced into the left common femoral artery through a 9 Fr sheath. Under fluoroscopic guidance, through an introducer sheath (GORE® DrySeal Sheath, W.L. GORE & Associates, Flagstaff, AZ), a 21 × 100 mm conformable thoracic aortic graft (cTAG) thoracic endoprosthesis (W.L. GORE & Associates); 25% oversizing to the aorta) was introduced through the right common femoral artery and deployed just below the level of the renal arteries under fluoroscopic guidance ().
A 14.5 × 100 mm branched iliac device (W.L. GORE & Associates) was then introduced via the right common femoral artery and deployed within the distal aspect of the cTAG device, ensuring that there was at least a 30-mm overlap. A 65-cm robotic remotely steerable coaxial catheter system (Hansen Medical, Mountain View, CA) was used to navigate the tortuous iliac anatomy and successfully cannulate the contralateral iliac branch. An 18 × 95 mm extension iliac limb (W.L. GORE & Associates) was then introduced over a stiff wire to extend into the left common iliac artery. The Palmaz XL unmounted stent with an expansion range of 14–25 mm (Cordis, Bridgewater, NJ) was loaded over Omega NV Valvuloplasty balloon catheter (Cook Medical, Bloomington, IN). The stent was partially deployed by manual inflation, followed by full deployment using an inflation device up to 2 atmosphere pressure. A Palmaz stent (Cordis) was positioned overlapping the two endograft devices to enhance the radial forces at the infrarenal portion and prevent future migration ( and ). Completion angiography revealed satisfactory appearance of the composite device with no evidence of an endoleak. There were no immediate postoperative complications.
Postoperatively, the patient made an excellent recovery and was discharged home on day 5. CT angiography at 1 and 6 months demonstrated good position of the infrarenal aortic endograft and exclusion of the aneurysm (). A small Type 2 endoleak from the inferior mesenteric artery was noted, which, along with the overall sac size, remained stable at the 6-month scan.
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pmc-6180879-1
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A 1-year-old male presented to our unit for ultrasonography of the abdomen with complaints of fever and diarrhoea for 2 days to rule out mesenteric adenitis. The clinical examination was normal, with no signs of dehydration. There was no significant clinical history.
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pmc-6180880-1
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A 22-year-old female in her first pregnancy was referred to our centre at 37 weeks menstrual age for obstetric ultrasonography to assess foetal wellbeing. The clinical history was unremarkable. Routine obstetric sonographic examination at 22 weeks gestation did not reveal any abnormality.
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pmc-6180882-1
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The patient is a 44-year-old immigrant male who presented to our institution with multiple masses in bilateral parotid glands, left greater than right. He had a history of neurocysticercosis, presumably owing to ingestion of uncooked pork in Mexico and had undergone a previous craniotomy with removal of the brain mass in Mexico. The patient had been vaccinated against tuberculosis, and subsequent work-up for systemic tuberculosis was negative. This new onset of bilateral parotid masses since his emigration to USA was presumed to represent cysticercosis lesions. A CT scan of the neck with i.v. contrast demonstrated bilateral parotid masses with a dominant, ring-enhancing, hypodense lesion in the left superficial parotid gland, which measured 3.0 × 2.9 cm (). A left superficial parotidectomy was performed, and upon pathological analysis, the peripherally enhancing lesion grossly appeared as a large yellowish fluid-filled cyst (). Micropathology revealed a squamous epithelium-lined cyst with lymphoepithelial complexes (brown islands) consistent with a lymphoepithelial cyst (). This raised the concern of HIV infection, which was confirmed with serological studies.
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pmc-6180884-1
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An 88-year-old male presented to the emergency department complaining of upper abdominal pain, malaise, fever (38. 1 °C) and rigors of increasing severity for the preceding 3 weeks. There was no prior history of abdominal surgery or trauma. He was febrile on presentation, with diffuse tenderness and guarding in his upper abdomen. His biochemistry revealed normal liver function except for neutrophil leukocytosis (8.2 K µl–1) and thrombocythaemia (487 × 109 l–l). His coagulation tests were within normal limits.
A CT scan demonstrated a thick-walled gallbladder containing numerous radiopaque calculi that was consistent with cholecystitis. This was complicated by an adjacent liver abscess and the suggestion of a localized gallbladder perforation. An ultrasound-guided drain insertion into the liver abscess was attempted and pus was aspirated; however, the patient did not tolerate the procedure and it was abandoned. There was no instrumentation of the gallbladder during this procedure. Initial plans to also drain the gallbladder were abandoned owing to patient refusal. However, his condition deteriorated with worsening sepsis and a repeat CT scan demonstrated increasing dimensions of the liver abscess and a high density focus within the gallbladder neck, at this point thought to represent a calculus (). Repeat ultrasound-guided drainage was attempted under sedation, which was successful, and blood-stained pus was aspirated. The blood staining was thought to be traumatic in nature.
The patient then developed melena and anaemia, and had an unremarkable upper gastrointestinal endoscopy. A CT angiogram demonstrated a 26 × 17 mm pseudoaneurysm arising from the cystic artery and haemobilia (). In retrospect, this was seen on prior imaging, where the lesion was misinterpreted as a calculus in the gallbladder neck. This CT scan revealed that the high density focus (pseudoaneurysm) had increased in size following the previous CT scan taken 1 week prior. Arterial anatomy showed a cystic artery that originated from the right hepatic artery as a branch of the superior mesenteric artery ().
In our institution, we would usually manage such pseudoaneurysms by either selectively coiling the feeding artery, filling the pseudoaneurysm sac with coils, placing a covered stent across the feeder or using embolic agents or thrombin. In this case, the aim was to selectively coil the feeding vessel via right common femoral artery puncture; however, it was not technically possible to engage a catheter into the sac and during the process of negotiation, the sac ruptured. The pseudoaneurysm was then embolized by instilling a mixture of 2 : 4 cyanoacrylate and lipiodol () into the cystic artery as an instant embolic agent and accept the risk of gallbladder necrosis. The right hepatic artery was preserved.
The patient made an uneventful immediate recovery following the embolization and appropriate antimicrobial treatment. The liver drain was removed a week later and he was discharged with oral antibiotics. Owing to his comorbidities and frailty, it was decided not to proceed to cholecystectomy. A follow-up ultrasound showed regression of the liver abscess and collapse of the gallbladder containing calculi.
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pmc-6180886-1
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A 29-year-old female was recently diagnosed with cancer of the cervix. She had a total hysterectomy and was scheduled for postoperative radiotherapy and chemotherapy. However, she developed urinary incontinence that led to cancellation of both the radiotherapy and chemotherapy sessions. An abdominopelvic CT scan was ordered to check for residual disease and confirm the cause of urinary incontinence.
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