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Surgery_Schwartz_3202
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in the biliary or urinary systems. Metal stents generally are delivered over a balloon and expanded with the balloon to the desired size. These metal stents usually are made of titanium or niti-nol and are still used in coronary stenting. A chemotherapeutic agent was added to coronary stents several years ago to decrease endothelial proliferation. These drug-eluting stents provide greater long-term patency but require long-term anticoagula-tion with antiplatelet agents to prevent thrombosis.82 Coated metal stents are used to prevent tissue ingrowth. Ingrowth may Brunicardi_Ch14_p0453-p0478.indd 46901/03/19 4:59 PM 470BASIC CONSIDERATIONSPART IFigure 14-23. This is an esophagram in a patient with severe dys-phagia secondary to advanced esophageal cancer (A) before and (B) after placement of a covered self-expanding metal stent.ABFigure 14-24. Covered self-expanding metal stents. These devices can be placed fluoroscopically or endoscopically.be an advantage in preventing stent
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Surgery_Schwartz. in the biliary or urinary systems. Metal stents generally are delivered over a balloon and expanded with the balloon to the desired size. These metal stents usually are made of titanium or niti-nol and are still used in coronary stenting. A chemotherapeutic agent was added to coronary stents several years ago to decrease endothelial proliferation. These drug-eluting stents provide greater long-term patency but require long-term anticoagula-tion with antiplatelet agents to prevent thrombosis.82 Coated metal stents are used to prevent tissue ingrowth. Ingrowth may Brunicardi_Ch14_p0453-p0478.indd 46901/03/19 4:59 PM 470BASIC CONSIDERATIONSPART IFigure 14-23. This is an esophagram in a patient with severe dys-phagia secondary to advanced esophageal cancer (A) before and (B) after placement of a covered self-expanding metal stent.ABFigure 14-24. Covered self-expanding metal stents. These devices can be placed fluoroscopically or endoscopically.be an advantage in preventing stent
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Surgery_Schwartz_3203
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of a covered self-expanding metal stent.ABFigure 14-24. Covered self-expanding metal stents. These devices can be placed fluoroscopically or endoscopically.be an advantage in preventing stent migration, but such tissue ingrowth may occlude the lumen and cause obstruction anew. This is a particular problem when stents are used for palliation of GI malignant growth and may be a problem for the long-term use of stents in vascular disease. Filling the interstices with Silastic or other materials may prevent tumor ingrowth but also makes stent migration more likely. In an effort to minimize stent migration, stents have been incorporated with hooks and barbs at the proximal end of the stent to anchor it to the wall of the vessel. Endovascular stenting of aortic aneurysms has nearly replaced open surgery for this condition. Lastly, self-expanding plastic stents have been developed as temporary devices to be used in the GI tract to close internal fistulas and bridge leaking
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Surgery_Schwartz. of a covered self-expanding metal stent.ABFigure 14-24. Covered self-expanding metal stents. These devices can be placed fluoroscopically or endoscopically.be an advantage in preventing stent migration, but such tissue ingrowth may occlude the lumen and cause obstruction anew. This is a particular problem when stents are used for palliation of GI malignant growth and may be a problem for the long-term use of stents in vascular disease. Filling the interstices with Silastic or other materials may prevent tumor ingrowth but also makes stent migration more likely. In an effort to minimize stent migration, stents have been incorporated with hooks and barbs at the proximal end of the stent to anchor it to the wall of the vessel. Endovascular stenting of aortic aneurysms has nearly replaced open surgery for this condition. Lastly, self-expanding plastic stents have been developed as temporary devices to be used in the GI tract to close internal fistulas and bridge leaking
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Surgery_Schwartz_3204
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replaced open surgery for this condition. Lastly, self-expanding plastic stents have been developed as temporary devices to be used in the GI tract to close internal fistulas and bridge leaking anastomoses.Natural Orifice Transluminal Endoscopic SurgeryThe use of the flexible endoscope to enter the GI, urinary, or reproductive tracts and then traverse the wall of the structure to enter the peritoneal cavity, the mediastinum, or the chest has strong appeal to patients wishing to avoid scars and pain caused by abdominal wall trauma. In truth, transluminal surgery has been performed in the stomach for a long time, either from the inside out (e.g., percutaneous, PEG, and transgastric pseudocyst drainage) or from the outside in (e.g., laparoscopic-assisted intragastric tumor resection). The catalyz-ing events for NOTES were the demonstration that a porcine gallbladder could be removed with a flexible endoscope passed through the wall of the stomach and then removed through the mouth and
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Surgery_Schwartz. replaced open surgery for this condition. Lastly, self-expanding plastic stents have been developed as temporary devices to be used in the GI tract to close internal fistulas and bridge leaking anastomoses.Natural Orifice Transluminal Endoscopic SurgeryThe use of the flexible endoscope to enter the GI, urinary, or reproductive tracts and then traverse the wall of the structure to enter the peritoneal cavity, the mediastinum, or the chest has strong appeal to patients wishing to avoid scars and pain caused by abdominal wall trauma. In truth, transluminal surgery has been performed in the stomach for a long time, either from the inside out (e.g., percutaneous, PEG, and transgastric pseudocyst drainage) or from the outside in (e.g., laparoscopic-assisted intragastric tumor resection). The catalyz-ing events for NOTES were the demonstration that a porcine gallbladder could be removed with a flexible endoscope passed through the wall of the stomach and then removed through the mouth and
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Surgery_Schwartz_3205
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catalyz-ing events for NOTES were the demonstration that a porcine gallbladder could be removed with a flexible endoscope passed through the wall of the stomach and then removed through the mouth and the demonstration in a series of 10 human cases from India of the ability to perform transgastric appendectomy. Since that time, a great deal of money has been invested by endo-scopic and MIS companies to help surgeons and gastroenterolo-gists explore this new territory. Systemic inflammatory markers such as C-reactive protein, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 have been shown to be similar in transgastric and transcolonic NOTES when compared to laparoscopy in por-cine models.83 Concerns about the safety of transluminal access and limitations in equipment remain the greatest barriers to expansion. To date, the most headline-grabbing procedures have been the transvaginal and transgastric removal of the gallbladder84-86 (Fig. 14-25). To ensure safety, all human cases
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Surgery_Schwartz. catalyz-ing events for NOTES were the demonstration that a porcine gallbladder could be removed with a flexible endoscope passed through the wall of the stomach and then removed through the mouth and the demonstration in a series of 10 human cases from India of the ability to perform transgastric appendectomy. Since that time, a great deal of money has been invested by endo-scopic and MIS companies to help surgeons and gastroenterolo-gists explore this new territory. Systemic inflammatory markers such as C-reactive protein, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 have been shown to be similar in transgastric and transcolonic NOTES when compared to laparoscopy in por-cine models.83 Concerns about the safety of transluminal access and limitations in equipment remain the greatest barriers to expansion. To date, the most headline-grabbing procedures have been the transvaginal and transgastric removal of the gallbladder84-86 (Fig. 14-25). To ensure safety, all human cases
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Surgery_Schwartz_3206
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barriers to expansion. To date, the most headline-grabbing procedures have been the transvaginal and transgastric removal of the gallbladder84-86 (Fig. 14-25). To ensure safety, all human cases thus far have involved laparoscopic assistance to aid in retrac-tion and ensure adequate closure of the stomach or vagina. To date, thousands of transvaginal and transgastric procedures have been performed internationally, with two large registries dem-onstrating noninferiority to conventional laparoscopy.87 The fact that the vast majority of these procedures are being done trans-vaginally creates an obvious limitation in applicability.The rapid growth of endoscopic technology catalyzed by NOTES has already spun off new technologies capable of performing a wide variety of endoscopic surgical procedures from EMR, to ablation of Barrett’s esophagus, to creation of competent antireflux valves in patients with gastroesophageal reflux disease.Peroral esophageal myotomy (POEM) has shown promise as a
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Surgery_Schwartz. barriers to expansion. To date, the most headline-grabbing procedures have been the transvaginal and transgastric removal of the gallbladder84-86 (Fig. 14-25). To ensure safety, all human cases thus far have involved laparoscopic assistance to aid in retrac-tion and ensure adequate closure of the stomach or vagina. To date, thousands of transvaginal and transgastric procedures have been performed internationally, with two large registries dem-onstrating noninferiority to conventional laparoscopy.87 The fact that the vast majority of these procedures are being done trans-vaginally creates an obvious limitation in applicability.The rapid growth of endoscopic technology catalyzed by NOTES has already spun off new technologies capable of performing a wide variety of endoscopic surgical procedures from EMR, to ablation of Barrett’s esophagus, to creation of competent antireflux valves in patients with gastroesophageal reflux disease.Peroral esophageal myotomy (POEM) has shown promise as a
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Surgery_Schwartz_3207
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from EMR, to ablation of Barrett’s esophagus, to creation of competent antireflux valves in patients with gastroesophageal reflux disease.Peroral esophageal myotomy (POEM) has shown promise as a NOTES treatment for esophageal achalasia.88 In this proce-dure, a 1.5to 2-cm mucosotomy is created within the anterior esophagus 10 cm proximal to the gastroesophageal junction. A submucosal tunnel is then created using a combination of elec-trocautery, hydrodissection, and carbon dioxide insufflation. The scope is advanced beyond the gastroesophageal junction, and a circular myotomy is performed avoiding disruption of the longitudinal fibers. The mucosotomy is then closed using endo-scopic clips (Fig. 14-26). Over 1000 clinical POEM cases have been performed worldwide. Data from expert NOTES surgeons suggest that this selective myotomy avoids abdominal trauma 4Brunicardi_Ch14_p0453-p0478.indd 47001/03/19 4:59 PM 471MINIMALLY INVASIVE SURGERYCHAPTER 14Figure 14-25. Transgastric
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Surgery_Schwartz. from EMR, to ablation of Barrett’s esophagus, to creation of competent antireflux valves in patients with gastroesophageal reflux disease.Peroral esophageal myotomy (POEM) has shown promise as a NOTES treatment for esophageal achalasia.88 In this proce-dure, a 1.5to 2-cm mucosotomy is created within the anterior esophagus 10 cm proximal to the gastroesophageal junction. A submucosal tunnel is then created using a combination of elec-trocautery, hydrodissection, and carbon dioxide insufflation. The scope is advanced beyond the gastroesophageal junction, and a circular myotomy is performed avoiding disruption of the longitudinal fibers. The mucosotomy is then closed using endo-scopic clips (Fig. 14-26). Over 1000 clinical POEM cases have been performed worldwide. Data from expert NOTES surgeons suggest that this selective myotomy avoids abdominal trauma 4Brunicardi_Ch14_p0453-p0478.indd 47001/03/19 4:59 PM 471MINIMALLY INVASIVE SURGERYCHAPTER 14Figure 14-25. Transgastric
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NOTES surgeons suggest that this selective myotomy avoids abdominal trauma 4Brunicardi_Ch14_p0453-p0478.indd 47001/03/19 4:59 PM 471MINIMALLY INVASIVE SURGERYCHAPTER 14Figure 14-25. Transgastric cholecystectomy using natural orifice transluminal endoscopic surgery technology and one to three laparoscopic ports has been performed occasionally in several locations around the world. (Reproduced with permission from The Johns Hopkins University School of Medicine, Baltimore, MD; 2007. Illustration by Jennifer Fairman.)and minimally disrupts the normal anatomic characteristics of the gastroesophageal junction while providing significant relief of symptoms.89 Randomized clinical trials and long-term follow-up need to be performed to further evaluate efficacy.Although this application is still considered experimen-tal, there is little doubt that when equivalent operations can be performed with less pain, fewer scars, and less disability, patients will flock to it. NOTES procedures are
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Surgery_Schwartz. NOTES surgeons suggest that this selective myotomy avoids abdominal trauma 4Brunicardi_Ch14_p0453-p0478.indd 47001/03/19 4:59 PM 471MINIMALLY INVASIVE SURGERYCHAPTER 14Figure 14-25. Transgastric cholecystectomy using natural orifice transluminal endoscopic surgery technology and one to three laparoscopic ports has been performed occasionally in several locations around the world. (Reproduced with permission from The Johns Hopkins University School of Medicine, Baltimore, MD; 2007. Illustration by Jennifer Fairman.)and minimally disrupts the normal anatomic characteristics of the gastroesophageal junction while providing significant relief of symptoms.89 Randomized clinical trials and long-term follow-up need to be performed to further evaluate efficacy.Although this application is still considered experimen-tal, there is little doubt that when equivalent operations can be performed with less pain, fewer scars, and less disability, patients will flock to it. NOTES procedures are
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considered experimen-tal, there is little doubt that when equivalent operations can be performed with less pain, fewer scars, and less disability, patients will flock to it. NOTES procedures are associated with an increased mental workload and significant learning curve for even experienced surgical endoscopists. Surgeons should engage only when they can perform these procedures with the safety and efficacy demanded by our profession.Single-Incision Laparoscopic SurgeryAs a surgical technique, SILS seems to be a natural progression from conventional laparoscopic surgery. As surgeons sought to reduce the number and size of abdominal wall trocars and NOTES procedures necessitated laparoscopic surveillance, the idea of a hybridization took off. An incision in the umbilicus, a preexisting scar, is thought to be less painful, have fewer wound complications, lead to quicker return to activity, and have a bet-ter cosmetic appearance than conventional laparoscopy. Per-haps one of the earliest
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Surgery_Schwartz. considered experimen-tal, there is little doubt that when equivalent operations can be performed with less pain, fewer scars, and less disability, patients will flock to it. NOTES procedures are associated with an increased mental workload and significant learning curve for even experienced surgical endoscopists. Surgeons should engage only when they can perform these procedures with the safety and efficacy demanded by our profession.Single-Incision Laparoscopic SurgeryAs a surgical technique, SILS seems to be a natural progression from conventional laparoscopic surgery. As surgeons sought to reduce the number and size of abdominal wall trocars and NOTES procedures necessitated laparoscopic surveillance, the idea of a hybridization took off. An incision in the umbilicus, a preexisting scar, is thought to be less painful, have fewer wound complications, lead to quicker return to activity, and have a bet-ter cosmetic appearance than conventional laparoscopy. Per-haps one of the earliest
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Surgery_Schwartz_3210
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is thought to be less painful, have fewer wound complications, lead to quicker return to activity, and have a bet-ter cosmetic appearance than conventional laparoscopy. Per-haps one of the earliest examples of SILS is the application of laparoscopic instrumentation to resect lesions in the rectum or sigmoid colon. Using the anus as the portal of entry, transanal endoscopic microsurgery (TEMS) employs a specialized mul-tichannel trocar to reach lesions located 8 to 18 cm away from the anal verge (Fig. 14-27).More deformable versions of these complex trocars have been developed with features to allow insufflation and be ame-nable to maintaining a seal within the natural orifice of the umbili-cus (see Fig. 14-11). Ports typically contain three or four channels. The latter often affords the ability to place a dedicated retractor.There are many challenges faced by the operating surgeon in SILS procedures. These include crowded trocar placement, a lack of triangulation of leftand
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Surgery_Schwartz. is thought to be less painful, have fewer wound complications, lead to quicker return to activity, and have a bet-ter cosmetic appearance than conventional laparoscopy. Per-haps one of the earliest examples of SILS is the application of laparoscopic instrumentation to resect lesions in the rectum or sigmoid colon. Using the anus as the portal of entry, transanal endoscopic microsurgery (TEMS) employs a specialized mul-tichannel trocar to reach lesions located 8 to 18 cm away from the anal verge (Fig. 14-27).More deformable versions of these complex trocars have been developed with features to allow insufflation and be ame-nable to maintaining a seal within the natural orifice of the umbili-cus (see Fig. 14-11). Ports typically contain three or four channels. The latter often affords the ability to place a dedicated retractor.There are many challenges faced by the operating surgeon in SILS procedures. These include crowded trocar placement, a lack of triangulation of leftand
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Surgery_Schwartz_3211
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the ability to place a dedicated retractor.There are many challenges faced by the operating surgeon in SILS procedures. These include crowded trocar placement, a lack of triangulation of leftand right-hand instruments, fre-quent crossing or clashing of instruments, limited visualiza-tion, and limited retraction ability. These challenges are mitigated by surgeon’s experience and the development of specialized instruments. Articulating or curved instruments of varying lengths and an extended length can improve working space. Curved instruments are typically reusable and offer less clutter than their more sophisticated counterparts, providing some cost reduction (Fig. 14-28). A low-profile HD scope with or without a deflect-able tip can improve visualization greatly. Even with such instru-mentation, the learning curve is very steep, particularly when the surgeon is forced to work in a cross-handed technique. The accomplished SILS surgeon will possess a tool bag of innovative
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Surgery_Schwartz. the ability to place a dedicated retractor.There are many challenges faced by the operating surgeon in SILS procedures. These include crowded trocar placement, a lack of triangulation of leftand right-hand instruments, fre-quent crossing or clashing of instruments, limited visualiza-tion, and limited retraction ability. These challenges are mitigated by surgeon’s experience and the development of specialized instruments. Articulating or curved instruments of varying lengths and an extended length can improve working space. Curved instruments are typically reusable and offer less clutter than their more sophisticated counterparts, providing some cost reduction (Fig. 14-28). A low-profile HD scope with or without a deflect-able tip can improve visualization greatly. Even with such instru-mentation, the learning curve is very steep, particularly when the surgeon is forced to work in a cross-handed technique. The accomplished SILS surgeon will possess a tool bag of innovative
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Surgery_Schwartz_3212
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instru-mentation, the learning curve is very steep, particularly when the surgeon is forced to work in a cross-handed technique. The accomplished SILS surgeon will possess a tool bag of innovative 5Brunicardi_Ch14_p0453-p0478.indd 47101/03/19 4:59 PM 472BASIC CONSIDERATIONSPART IFigure 14-28. Example of curved instruments used in single-incision laparoscopic surgery. (© 2013 Intuitive Surgical, Inc. Reprinted with permission.)Figure 14-26. A. Peroral endoscopic esophageal myotomy for the treatment of achalasia. (Reproduced with permission from Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myot-omy (POEM) for esophageal achalasia, Endoscopy. 2010 Apr; 42(4):265-271.) B. Serial images showing overtube in submuco-sal tunnel, using needle knife to divide circular muscle fibers of esophagus, and closure of myotomy with clips. (Reproduced with permission from Rieder E, Dunst CM, Kastenmeier AS, et al: Devel-opment and technique of per oral endoscopic myotomy (POEM) for
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Surgery_Schwartz. instru-mentation, the learning curve is very steep, particularly when the surgeon is forced to work in a cross-handed technique. The accomplished SILS surgeon will possess a tool bag of innovative 5Brunicardi_Ch14_p0453-p0478.indd 47101/03/19 4:59 PM 472BASIC CONSIDERATIONSPART IFigure 14-28. Example of curved instruments used in single-incision laparoscopic surgery. (© 2013 Intuitive Surgical, Inc. Reprinted with permission.)Figure 14-26. A. Peroral endoscopic esophageal myotomy for the treatment of achalasia. (Reproduced with permission from Inoue H, Minami H, Kobayashi Y, et al. Peroral endoscopic myot-omy (POEM) for esophageal achalasia, Endoscopy. 2010 Apr; 42(4):265-271.) B. Serial images showing overtube in submuco-sal tunnel, using needle knife to divide circular muscle fibers of esophagus, and closure of myotomy with clips. (Reproduced with permission from Rieder E, Dunst CM, Kastenmeier AS, et al: Devel-opment and technique of per oral endoscopic myotomy (POEM) for
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Surgery_Schwartz_3213
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of esophagus, and closure of myotomy with clips. (Reproduced with permission from Rieder E, Dunst CM, Kastenmeier AS, et al: Devel-opment and technique of per oral endoscopic myotomy (POEM) for achala, Eur Surg 2011 June;43(3):140–145.) ABFigure 14-27. Transanal endoscopic microsurgery scope. (Repro-duced with permission from The Johns Hopkins University School of Medicine, Baltimore, MD; 2014. Illustration by Corinne Sandone.)strategies to retract structures like the gallbladder away from the operative field. These tricks may range from the use of percutane-ous needlescopic instruments to the application of transfascial sutures. Expert consensus recommendations for efficient SILS are shown in Tables 14-3 and 14-4.8 When performing SILS proce-dures, it is imperative to follow proven tenets of operative con-duct such as visualizing the “critical view” of safety in a laparoscopic cholecystectomy. As safety should always be the paramount concern, the addition of extra trocars or
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Surgery_Schwartz. of esophagus, and closure of myotomy with clips. (Reproduced with permission from Rieder E, Dunst CM, Kastenmeier AS, et al: Devel-opment and technique of per oral endoscopic myotomy (POEM) for achala, Eur Surg 2011 June;43(3):140–145.) ABFigure 14-27. Transanal endoscopic microsurgery scope. (Repro-duced with permission from The Johns Hopkins University School of Medicine, Baltimore, MD; 2014. Illustration by Corinne Sandone.)strategies to retract structures like the gallbladder away from the operative field. These tricks may range from the use of percutane-ous needlescopic instruments to the application of transfascial sutures. Expert consensus recommendations for efficient SILS are shown in Tables 14-3 and 14-4.8 When performing SILS proce-dures, it is imperative to follow proven tenets of operative con-duct such as visualizing the “critical view” of safety in a laparoscopic cholecystectomy. As safety should always be the paramount concern, the addition of extra trocars or
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Surgery_Schwartz_3214
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tenets of operative con-duct such as visualizing the “critical view” of safety in a laparoscopic cholecystectomy. As safety should always be the paramount concern, the addition of extra trocars or conversion to traditional laparoscopy should not be considered a failure.Contraindications include those true of traditional lapa-roscopy. Relative contraindications include previous surgery and high body mass index (BMI). Patients with a high BMI or central obesity can pose a challenge because the umbilicus may be located far from operative target. Size and morphology of the target organ should always be considered when doing SILS.Many studies have demonstrated equivalency to standard laparoscopic procedures regarding intraoperative and postop-erative complications. However, it is questionable what the full benefit of the dramatic reduction in ergonomics and the increase in complexity provide beyond an improved cosmetic appear-ance. This is in large part due to the already improved benefits
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Surgery_Schwartz. tenets of operative con-duct such as visualizing the “critical view” of safety in a laparoscopic cholecystectomy. As safety should always be the paramount concern, the addition of extra trocars or conversion to traditional laparoscopy should not be considered a failure.Contraindications include those true of traditional lapa-roscopy. Relative contraindications include previous surgery and high body mass index (BMI). Patients with a high BMI or central obesity can pose a challenge because the umbilicus may be located far from operative target. Size and morphology of the target organ should always be considered when doing SILS.Many studies have demonstrated equivalency to standard laparoscopic procedures regarding intraoperative and postop-erative complications. However, it is questionable what the full benefit of the dramatic reduction in ergonomics and the increase in complexity provide beyond an improved cosmetic appear-ance. This is in large part due to the already improved benefits
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Surgery_Schwartz_3215
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the full benefit of the dramatic reduction in ergonomics and the increase in complexity provide beyond an improved cosmetic appear-ance. This is in large part due to the already improved benefits of laparoscopic surgery.A meta-analysis performed by Ahmed and colleagues in 2010 found the conversion rate from SILS to conventional lapa-roscopy to be 0% to 24% for cholecystectomies, 0% to 41% Table 14-3Expert panel recommendations for accomplishing single-incision laparoscopic surgery efficientlyMultichannel port preferably to be placed intraumbilically, but an extraumbilical approach can be used in certain casesExtra ports should be used where there is a clinical needWhen applicable, sutures can be useful for added retractionClosure should be accomplished using sutures of absorbable material placed either continuously or interruptedSkin should be closed with absorbable sutures or glueReproduced with permission from Ahmed I, Cianco F, Ferrar V, et al. Current status of single-incision
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Surgery_Schwartz. the full benefit of the dramatic reduction in ergonomics and the increase in complexity provide beyond an improved cosmetic appear-ance. This is in large part due to the already improved benefits of laparoscopic surgery.A meta-analysis performed by Ahmed and colleagues in 2010 found the conversion rate from SILS to conventional lapa-roscopy to be 0% to 24% for cholecystectomies, 0% to 41% Table 14-3Expert panel recommendations for accomplishing single-incision laparoscopic surgery efficientlyMultichannel port preferably to be placed intraumbilically, but an extraumbilical approach can be used in certain casesExtra ports should be used where there is a clinical needWhen applicable, sutures can be useful for added retractionClosure should be accomplished using sutures of absorbable material placed either continuously or interruptedSkin should be closed with absorbable sutures or glueReproduced with permission from Ahmed I, Cianco F, Ferrar V, et al. Current status of single-incision
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placed either continuously or interruptedSkin should be closed with absorbable sutures or glueReproduced with permission from Ahmed I, Cianco F, Ferrar V, et al. Current status of single-incision laparoscopic surgery: European experts’ views, Surg Laparosc Endosc Percutan Tech. 2012 Jun;22(3):194-199.Brunicardi_Ch14_p0453-p0478.indd 47201/03/19 4:59 PM 473MINIMALLY INVASIVE SURGERYCHAPTER 14Figure 14-29. A and B. Robotic single-incision surgery platform. (©2013 Intuitive Surgical, Inc. Reprinted with permission.)ABTable 14-4Expert panel recommendations for single-incision laparoscopic surgery equipment and instrumentationRECOMMENDED EQUIPMENT/INSTRUMENTATIONBENEFIT TO SURGEONSlimline instruments with low-profile designReduces internal and external clashingVaried-length instrumentsReduces extracorporeal clashingLonger instrumentsAdvantageous for reaching the surgical fieldArticulating (or prebent) instrumentsRestore triangulationSmall-diameter, low-profile angle scopeReduces
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Surgery_Schwartz. placed either continuously or interruptedSkin should be closed with absorbable sutures or glueReproduced with permission from Ahmed I, Cianco F, Ferrar V, et al. Current status of single-incision laparoscopic surgery: European experts’ views, Surg Laparosc Endosc Percutan Tech. 2012 Jun;22(3):194-199.Brunicardi_Ch14_p0453-p0478.indd 47201/03/19 4:59 PM 473MINIMALLY INVASIVE SURGERYCHAPTER 14Figure 14-29. A and B. Robotic single-incision surgery platform. (©2013 Intuitive Surgical, Inc. Reprinted with permission.)ABTable 14-4Expert panel recommendations for single-incision laparoscopic surgery equipment and instrumentationRECOMMENDED EQUIPMENT/INSTRUMENTATIONBENEFIT TO SURGEONSlimline instruments with low-profile designReduces internal and external clashingVaried-length instrumentsReduces extracorporeal clashingLonger instrumentsAdvantageous for reaching the surgical fieldArticulating (or prebent) instrumentsRestore triangulationSmall-diameter, low-profile angle scopeReduces
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extracorporeal clashingLonger instrumentsAdvantageous for reaching the surgical fieldArticulating (or prebent) instrumentsRestore triangulationSmall-diameter, low-profile angle scopeReduces clashing by providing additional spaceHigh-definition cameraAchieves high-quality images for intraoperative visualizationReproduced with permission from Ahmed I, Cianco F, Ferrar V, et al. Current status of single-incision laparoscopic surgery: European experts’ views, Surg Laparosc Endosc Percutan Tech. 2012 Jun;22(3):194-199.for appendectomies, and 0% to 33% for nephrectomies.90 The most common complications were intra-abdominal abscesses and wound infections. Existing and emerging robotics platforms may provide the bridge necessary to bypass the significant tech-nical skills learning curve required to operate through a single site (Fig. 14-29).SPECIAL CONSIDERATIONSPediatric LaparoscopyThe advantages of MIS in children may be more significant than in the adult population. MIS in the adolescent
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Surgery_Schwartz. extracorporeal clashingLonger instrumentsAdvantageous for reaching the surgical fieldArticulating (or prebent) instrumentsRestore triangulationSmall-diameter, low-profile angle scopeReduces clashing by providing additional spaceHigh-definition cameraAchieves high-quality images for intraoperative visualizationReproduced with permission from Ahmed I, Cianco F, Ferrar V, et al. Current status of single-incision laparoscopic surgery: European experts’ views, Surg Laparosc Endosc Percutan Tech. 2012 Jun;22(3):194-199.for appendectomies, and 0% to 33% for nephrectomies.90 The most common complications were intra-abdominal abscesses and wound infections. Existing and emerging robotics platforms may provide the bridge necessary to bypass the significant tech-nical skills learning curve required to operate through a single site (Fig. 14-29).SPECIAL CONSIDERATIONSPediatric LaparoscopyThe advantages of MIS in children may be more significant than in the adult population. MIS in the adolescent
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to operate through a single site (Fig. 14-29).SPECIAL CONSIDERATIONSPediatric LaparoscopyThe advantages of MIS in children may be more significant than in the adult population. MIS in the adolescent is little dif-ferent from that in the adult, and standard instrumentation and trocar positions usually can be used. However, laparoscopy in the infant and young child requires specialized instrumentation. The instruments are shorter (15–20 cm), and many are 3 mm in diameter rather than 5 mm. Because the abdomen of the child is much smaller than that of the adult, a 5-mm telescope pro-vides sufficient illumination for most operations. The develop-ment of 5-mm clippers and bipolar devices has obviated the need for 10-mm trocars in pediatric laparoscopy.91 Because the abdominal wall is much thinner in infants, a pneumoperitoneum pressure of 8 mmHg can provide adequate exposure. DVT is rare in children, so prophylaxis against thrombosis probably is unnecessary. A wide variety of pediatric
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Surgery_Schwartz. to operate through a single site (Fig. 14-29).SPECIAL CONSIDERATIONSPediatric LaparoscopyThe advantages of MIS in children may be more significant than in the adult population. MIS in the adolescent is little dif-ferent from that in the adult, and standard instrumentation and trocar positions usually can be used. However, laparoscopy in the infant and young child requires specialized instrumentation. The instruments are shorter (15–20 cm), and many are 3 mm in diameter rather than 5 mm. Because the abdomen of the child is much smaller than that of the adult, a 5-mm telescope pro-vides sufficient illumination for most operations. The develop-ment of 5-mm clippers and bipolar devices has obviated the need for 10-mm trocars in pediatric laparoscopy.91 Because the abdominal wall is much thinner in infants, a pneumoperitoneum pressure of 8 mmHg can provide adequate exposure. DVT is rare in children, so prophylaxis against thrombosis probably is unnecessary. A wide variety of pediatric
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Surgery_Schwartz_3219
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in infants, a pneumoperitoneum pressure of 8 mmHg can provide adequate exposure. DVT is rare in children, so prophylaxis against thrombosis probably is unnecessary. A wide variety of pediatric surgical procedures are frequently performed with MIS access, from pull-through procedures for colonic aganglionosis (Hirschsprung’s disease) to repair of congenital diaphragmatic hernias.92Laparoscopy During PregnancyConcerns about the safety of laparoscopic cholecystectomy or appendectomy in the pregnant patient have been thoroughly investigated and are readily managed. Access to the abdomen in the pregnant patient should take into consideration the height of the uterine fundus, which reaches the umbilicus at 20 weeks. In order not to damage the uterus or its blood supply, most surgeons feel that the open (Hasson) approach should be 6used in favor of direct puncture laparoscopy. The patient should be positioned slightly on the left side to avoid compression of the vena cava by the uterus.
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Surgery_Schwartz. in infants, a pneumoperitoneum pressure of 8 mmHg can provide adequate exposure. DVT is rare in children, so prophylaxis against thrombosis probably is unnecessary. A wide variety of pediatric surgical procedures are frequently performed with MIS access, from pull-through procedures for colonic aganglionosis (Hirschsprung’s disease) to repair of congenital diaphragmatic hernias.92Laparoscopy During PregnancyConcerns about the safety of laparoscopic cholecystectomy or appendectomy in the pregnant patient have been thoroughly investigated and are readily managed. Access to the abdomen in the pregnant patient should take into consideration the height of the uterine fundus, which reaches the umbilicus at 20 weeks. In order not to damage the uterus or its blood supply, most surgeons feel that the open (Hasson) approach should be 6used in favor of direct puncture laparoscopy. The patient should be positioned slightly on the left side to avoid compression of the vena cava by the uterus.
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the open (Hasson) approach should be 6used in favor of direct puncture laparoscopy. The patient should be positioned slightly on the left side to avoid compression of the vena cava by the uterus. Because pregnancy poses a risk for thromboembolism, sequential compression devices are essential for all procedures. Fetal acidosis induced by maternal hypercar-bia also has been raised as a concern. The arterial pH of the fetus follows the pH of the mother linearly; and therefore, fetal acido-sis may be prevented by avoiding a respiratory acidosis in the mother.93 The pneumoperitoneum pressure induced by laparos-copy is not a safety issue either as it has been proved that mid-pregnancy uterine contractions provide a much greater pressure in utero than a pneumoperitoneum of 15 mmHg. More than 100 cases of laparoscopic cholecystectomy in pregnancy have been reported with uniformly good results.94 The operation should be performed during the second trimester of pregnancy if possible.
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Surgery_Schwartz. the open (Hasson) approach should be 6used in favor of direct puncture laparoscopy. The patient should be positioned slightly on the left side to avoid compression of the vena cava by the uterus. Because pregnancy poses a risk for thromboembolism, sequential compression devices are essential for all procedures. Fetal acidosis induced by maternal hypercar-bia also has been raised as a concern. The arterial pH of the fetus follows the pH of the mother linearly; and therefore, fetal acido-sis may be prevented by avoiding a respiratory acidosis in the mother.93 The pneumoperitoneum pressure induced by laparos-copy is not a safety issue either as it has been proved that mid-pregnancy uterine contractions provide a much greater pressure in utero than a pneumoperitoneum of 15 mmHg. More than 100 cases of laparoscopic cholecystectomy in pregnancy have been reported with uniformly good results.94 The operation should be performed during the second trimester of pregnancy if possible.
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than 100 cases of laparoscopic cholecystectomy in pregnancy have been reported with uniformly good results.94 The operation should be performed during the second trimester of pregnancy if possible. Protection of the fetus against intraoperative X-rays Brunicardi_Ch14_p0453-p0478.indd 47301/03/19 4:59 PM 474BASIC CONSIDERATIONSPART Iis imperative. Some believe it advisable to track fetal pulse rates with a transvaginal ultrasound probe; however, the significance of fetal tachycardia or bradycardia is a bit unclear in the second trimester of pregnancy. To be prudent, however, heart rate decelerations reversibly associated with pneumoperitoneum cre-ation might signal the need to convert to open cholecystectomy or appendectomy.Minimally Invasive Surgery and Cancer TreatmentMIS techniques have been used for many decades to provide palliation for the patient with an obstructive cancer. Laser treat-ment, intracavitary radiation, stenting, and dilation are outpa-tient techniques that
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Surgery_Schwartz. than 100 cases of laparoscopic cholecystectomy in pregnancy have been reported with uniformly good results.94 The operation should be performed during the second trimester of pregnancy if possible. Protection of the fetus against intraoperative X-rays Brunicardi_Ch14_p0453-p0478.indd 47301/03/19 4:59 PM 474BASIC CONSIDERATIONSPART Iis imperative. Some believe it advisable to track fetal pulse rates with a transvaginal ultrasound probe; however, the significance of fetal tachycardia or bradycardia is a bit unclear in the second trimester of pregnancy. To be prudent, however, heart rate decelerations reversibly associated with pneumoperitoneum cre-ation might signal the need to convert to open cholecystectomy or appendectomy.Minimally Invasive Surgery and Cancer TreatmentMIS techniques have been used for many decades to provide palliation for the patient with an obstructive cancer. Laser treat-ment, intracavitary radiation, stenting, and dilation are outpa-tient techniques that
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have been used for many decades to provide palliation for the patient with an obstructive cancer. Laser treat-ment, intracavitary radiation, stenting, and dilation are outpa-tient techniques that can be used to reestablish the continuity of an obstructed esophagus, bile duct, ureter, or airway. MIS techniques also have been used in the staging of cancer. Medias-tinoscopy is still used occasionally before thoracotomy to assess the status of the mediastinal lymph nodes. Laparoscopy also is used to assess the liver in patients being evaluated for pancre-atic, gastric, or hepatic resection. New technology and greater surgical skills allow for accurate minimally invasive staging of cancer.95 Occasionally, it is appropriate to perform pallia-tive measures (e.g., laparoscopic gastrojejunostomy to bypass a pancreatic cancer) at the time of diagnostic laparoscopy if diag-nostic findings preclude attempts at curative resection.Initially controversial, the role of MIS to provide a safe curative
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Surgery_Schwartz. have been used for many decades to provide palliation for the patient with an obstructive cancer. Laser treat-ment, intracavitary radiation, stenting, and dilation are outpa-tient techniques that can be used to reestablish the continuity of an obstructed esophagus, bile duct, ureter, or airway. MIS techniques also have been used in the staging of cancer. Medias-tinoscopy is still used occasionally before thoracotomy to assess the status of the mediastinal lymph nodes. Laparoscopy also is used to assess the liver in patients being evaluated for pancre-atic, gastric, or hepatic resection. New technology and greater surgical skills allow for accurate minimally invasive staging of cancer.95 Occasionally, it is appropriate to perform pallia-tive measures (e.g., laparoscopic gastrojejunostomy to bypass a pancreatic cancer) at the time of diagnostic laparoscopy if diag-nostic findings preclude attempts at curative resection.Initially controversial, the role of MIS to provide a safe curative
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bypass a pancreatic cancer) at the time of diagnostic laparoscopy if diag-nostic findings preclude attempts at curative resection.Initially controversial, the role of MIS to provide a safe curative treatment of cancer has proven to be no different from the principles of open surgery. All gross and microscopic tumor should be removed (an R0 resection), and an ade-quate lymphadenectomy should be performed to allow accurate staging. Generally, this number has been 10 to 15 lymph nodes, although there is still debate as to the value of more extensive lymphadenectomy. All of the major abdominal cancer opera-tions have been performed with laparoscopy. Of the three major cancer resections of GI cancer (liver lobe, pancreatic head, and esophagus), only esophagectomy is routinely performed by a fair number of centers.96,97 Laparoscopic hepatectomy has attracted a loyal following, and distal pancreatectomy frequently is performed with laparoscopic access. In Japan, laparoscopic-assisted
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Surgery_Schwartz. bypass a pancreatic cancer) at the time of diagnostic laparoscopy if diag-nostic findings preclude attempts at curative resection.Initially controversial, the role of MIS to provide a safe curative treatment of cancer has proven to be no different from the principles of open surgery. All gross and microscopic tumor should be removed (an R0 resection), and an ade-quate lymphadenectomy should be performed to allow accurate staging. Generally, this number has been 10 to 15 lymph nodes, although there is still debate as to the value of more extensive lymphadenectomy. All of the major abdominal cancer opera-tions have been performed with laparoscopy. Of the three major cancer resections of GI cancer (liver lobe, pancreatic head, and esophagus), only esophagectomy is routinely performed by a fair number of centers.96,97 Laparoscopic hepatectomy has attracted a loyal following, and distal pancreatectomy frequently is performed with laparoscopic access. In Japan, laparoscopic-assisted
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by a fair number of centers.96,97 Laparoscopic hepatectomy has attracted a loyal following, and distal pancreatectomy frequently is performed with laparoscopic access. In Japan, laparoscopic-assisted gastrectomy has become quite popular for early gastric cancer, an epidemic in Japan far exceeding that of colon cancer in North America and Northern Europe. The most common can-cer operation performed laparoscopically is segmental colec-tomy, which has proven itself safe and efficacious in a multicenter, controlled, randomized trial.98Considerations in the Elderly and InfirmLaparoscopic cholecystectomy has made possible the removal of a symptomatic gallbladder in many patients previously thought to be too elderly or too ill to undergo a laparotomy. Older patients are more likely to require conversion to lapa-rotomy because of disease chronicity.98Operations on these patients require close monitoring of anesthesia. The intraoperative management of these patients may be more difficult with
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Surgery_Schwartz. by a fair number of centers.96,97 Laparoscopic hepatectomy has attracted a loyal following, and distal pancreatectomy frequently is performed with laparoscopic access. In Japan, laparoscopic-assisted gastrectomy has become quite popular for early gastric cancer, an epidemic in Japan far exceeding that of colon cancer in North America and Northern Europe. The most common can-cer operation performed laparoscopically is segmental colec-tomy, which has proven itself safe and efficacious in a multicenter, controlled, randomized trial.98Considerations in the Elderly and InfirmLaparoscopic cholecystectomy has made possible the removal of a symptomatic gallbladder in many patients previously thought to be too elderly or too ill to undergo a laparotomy. Older patients are more likely to require conversion to lapa-rotomy because of disease chronicity.98Operations on these patients require close monitoring of anesthesia. The intraoperative management of these patients may be more difficult with
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Surgery_Schwartz_3225
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to lapa-rotomy because of disease chronicity.98Operations on these patients require close monitoring of anesthesia. The intraoperative management of these patients may be more difficult with laparoscopic access than with open access. The advantage of MIS lies in what happens after the operation. Much of the morbidity of surgery in the elderly is a result of impaired mobility. In addition, pulmonary compli-cations, urinary tract sepsis, DVT, pulmonary embolism, con-gestive heart failure, and myocardial infarction often are the result of improper fluid management and decreased mobility. By allowing rapid and early mobilization, laparoscopic surgery 7has made possible the safe performance of procedures in the elderly and infirm.Cirrhosis and Portal HypertensionPatients with hepatic insufficiency pose a significant challenge for any type of surgical intervention.99 The ultimate surgical out-come in this population relates directly to the degree of under-lying hepatic dysfunction.100
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Surgery_Schwartz. to lapa-rotomy because of disease chronicity.98Operations on these patients require close monitoring of anesthesia. The intraoperative management of these patients may be more difficult with laparoscopic access than with open access. The advantage of MIS lies in what happens after the operation. Much of the morbidity of surgery in the elderly is a result of impaired mobility. In addition, pulmonary compli-cations, urinary tract sepsis, DVT, pulmonary embolism, con-gestive heart failure, and myocardial infarction often are the result of improper fluid management and decreased mobility. By allowing rapid and early mobilization, laparoscopic surgery 7has made possible the safe performance of procedures in the elderly and infirm.Cirrhosis and Portal HypertensionPatients with hepatic insufficiency pose a significant challenge for any type of surgical intervention.99 The ultimate surgical out-come in this population relates directly to the degree of under-lying hepatic dysfunction.100
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pose a significant challenge for any type of surgical intervention.99 The ultimate surgical out-come in this population relates directly to the degree of under-lying hepatic dysfunction.100 Often, this group of patients has minimal reserve, and the stress of an operation will trigger com-plete hepatic failure or hepatorenal syndrome. These patients are at risk for major hemorrhage at all levels, including trocar insertion, operative dissection in a field of dilated veins, and secondary to an underlying coagulopathy. Additionally, ascitic leak from a port site may occur, leading to bacterial peritonitis. Therefore, a watertight port site closure should be carried out in all patients.It is essential that the surgeon be aware of the severity of hepatic cirrhosis as judged by a Model of End-Stage Liver Dis-ease (MELD) score or Child’s classification. Additionally, the presence of portal hypertension is a relative contraindication to laparoscopic surgery until the portal pressures are
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Surgery_Schwartz. pose a significant challenge for any type of surgical intervention.99 The ultimate surgical out-come in this population relates directly to the degree of under-lying hepatic dysfunction.100 Often, this group of patients has minimal reserve, and the stress of an operation will trigger com-plete hepatic failure or hepatorenal syndrome. These patients are at risk for major hemorrhage at all levels, including trocar insertion, operative dissection in a field of dilated veins, and secondary to an underlying coagulopathy. Additionally, ascitic leak from a port site may occur, leading to bacterial peritonitis. Therefore, a watertight port site closure should be carried out in all patients.It is essential that the surgeon be aware of the severity of hepatic cirrhosis as judged by a Model of End-Stage Liver Dis-ease (MELD) score or Child’s classification. Additionally, the presence of portal hypertension is a relative contraindication to laparoscopic surgery until the portal pressures are
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Liver Dis-ease (MELD) score or Child’s classification. Additionally, the presence of portal hypertension is a relative contraindication to laparoscopic surgery until the portal pressures are reduced with portal decompression. For example, if a patient has an incarcer-ated umbilical hernia and ascites, a preoperative paracentesis or transjugular intrahepatic portosystemic shunt procedure in con-junction with aggressive diuresis may be considered. Because these patients commonly are intravascularly depleted, insuffla-tion pressures should be reduced to prevent a decrease in cardiac output, and minimal amounts of Na+-sparing IV fluids should be given.Economics of Minimally Invasive SurgeryMinimally invasive surgical procedures reduce the costs of sur-gery most when length of hospital stay can be shortened and return to work is quickened. For example, shorter hospital stays can be demonstrated in laparoscopic cholecystectomy, Nissen fundoplication, splenectomy, and adrenalectomy.
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Surgery_Schwartz. Liver Dis-ease (MELD) score or Child’s classification. Additionally, the presence of portal hypertension is a relative contraindication to laparoscopic surgery until the portal pressures are reduced with portal decompression. For example, if a patient has an incarcer-ated umbilical hernia and ascites, a preoperative paracentesis or transjugular intrahepatic portosystemic shunt procedure in con-junction with aggressive diuresis may be considered. Because these patients commonly are intravascularly depleted, insuffla-tion pressures should be reduced to prevent a decrease in cardiac output, and minimal amounts of Na+-sparing IV fluids should be given.Economics of Minimally Invasive SurgeryMinimally invasive surgical procedures reduce the costs of sur-gery most when length of hospital stay can be shortened and return to work is quickened. For example, shorter hospital stays can be demonstrated in laparoscopic cholecystectomy, Nissen fundoplication, splenectomy, and adrenalectomy.
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stay can be shortened and return to work is quickened. For example, shorter hospital stays can be demonstrated in laparoscopic cholecystectomy, Nissen fundoplication, splenectomy, and adrenalectomy. Procedures such as inguinal herniorrhaphy that are already performed as outpatient procedures are less likely to provide cost savings. Procedures that still require a 4to 7-day hospitalization, such as laparoscopy-assisted colectomy, are less likely to deliver a lower bottom line than their open surgery counterparts. None-theless, with responsible use of disposable instrumentation and a commitment to the most effective use of the inpatient setting, most laparoscopic procedures can be made less expensive than their conventional equivalents.Education and Skill AcquisitionHistorically, surgeons in training (residents, registrars, and fel-lows) acquired their skills in minimally invasive techniques through a series of operative experiences of graded complexity. This training occurred on
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Surgery_Schwartz. stay can be shortened and return to work is quickened. For example, shorter hospital stays can be demonstrated in laparoscopic cholecystectomy, Nissen fundoplication, splenectomy, and adrenalectomy. Procedures such as inguinal herniorrhaphy that are already performed as outpatient procedures are less likely to provide cost savings. Procedures that still require a 4to 7-day hospitalization, such as laparoscopy-assisted colectomy, are less likely to deliver a lower bottom line than their open surgery counterparts. None-theless, with responsible use of disposable instrumentation and a commitment to the most effective use of the inpatient setting, most laparoscopic procedures can be made less expensive than their conventional equivalents.Education and Skill AcquisitionHistorically, surgeons in training (residents, registrars, and fel-lows) acquired their skills in minimally invasive techniques through a series of operative experiences of graded complexity. This training occurred on
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in training (residents, registrars, and fel-lows) acquired their skills in minimally invasive techniques through a series of operative experiences of graded complexity. This training occurred on patients. Although such a paradigm did not compromise patient safety, learning in the OR is costly. In addition, the recent worldwide constraint placed on resident work hours makes it attractive to teach laparoscopic skills out-side of the OR.Skills labs started at nearly every surgical training center in the 1990s with low fidelity box-type trainers. These were rudimentary simulated abdominal cavities with a video camera, monitor, trocars, laparoscopic instruments, and target models. These targets were often as simple as a pegboard and rubber rings, or a latex drain to practice suturing and knot tying. Virtual reality training devices present a unique opportunity to improve and enhance experiential learning in endoscopy and laparoscopy Brunicardi_Ch14_p0453-p0478.indd 47401/03/19 4:59 PM
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Surgery_Schwartz. in training (residents, registrars, and fel-lows) acquired their skills in minimally invasive techniques through a series of operative experiences of graded complexity. This training occurred on patients. Although such a paradigm did not compromise patient safety, learning in the OR is costly. In addition, the recent worldwide constraint placed on resident work hours makes it attractive to teach laparoscopic skills out-side of the OR.Skills labs started at nearly every surgical training center in the 1990s with low fidelity box-type trainers. These were rudimentary simulated abdominal cavities with a video camera, monitor, trocars, laparoscopic instruments, and target models. These targets were often as simple as a pegboard and rubber rings, or a latex drain to practice suturing and knot tying. Virtual reality training devices present a unique opportunity to improve and enhance experiential learning in endoscopy and laparoscopy Brunicardi_Ch14_p0453-p0478.indd 47401/03/19 4:59 PM
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tying. Virtual reality training devices present a unique opportunity to improve and enhance experiential learning in endoscopy and laparoscopy Brunicardi_Ch14_p0453-p0478.indd 47401/03/19 4:59 PM 475MINIMALLY INVASIVE SURGERYCHAPTER 14Figure 14-30. The progress of general sur-gery can be reflected by a series of performance curves. General anesthesia and sterile technique allowed the development of maximally inva-sive open surgery over the last 125 years. Video optics allowed the development of minimally invasive surgery over the last 25 years. Nonin-vasive (seamless) surgery will result when a yet undiscovered transformational event allows sur-gery to occur without an incision, and perhaps without anesthesia.PerformanceGeneral anesthesiasterile techniqueVideo optics?1880190019201940196019801985199019952000??Open surgeryLaparoscopic surgerySeamless surgeryProgress in surgeryfor all surgeons. This technology has the advantage of enabling objective measurement of psychomotor skills,
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Surgery_Schwartz. tying. Virtual reality training devices present a unique opportunity to improve and enhance experiential learning in endoscopy and laparoscopy Brunicardi_Ch14_p0453-p0478.indd 47401/03/19 4:59 PM 475MINIMALLY INVASIVE SURGERYCHAPTER 14Figure 14-30. The progress of general sur-gery can be reflected by a series of performance curves. General anesthesia and sterile technique allowed the development of maximally inva-sive open surgery over the last 125 years. Video optics allowed the development of minimally invasive surgery over the last 25 years. Nonin-vasive (seamless) surgery will result when a yet undiscovered transformational event allows sur-gery to occur without an incision, and perhaps without anesthesia.PerformanceGeneral anesthesiasterile techniqueVideo optics?1880190019201940196019801985199019952000??Open surgeryLaparoscopic surgerySeamless surgeryProgress in surgeryfor all surgeons. This technology has the advantage of enabling objective measurement of psychomotor skills,
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surgeryLaparoscopic surgerySeamless surgeryProgress in surgeryfor all surgeons. This technology has the advantage of enabling objective measurement of psychomotor skills, which can be used to determine progress in skill acquisition and, ultimately, techni-cal competency.101 Several of these devices have been validated as a means of measuring proficiency in skill performance. More importantly, training on virtual reality platforms has proven to translate to improved operative performance in randomized tri-als.102,103 Currently, surgical skills labs are mandatory for Resi-dency Review Committee credentialing. Successful completion of the Fundamentals of Laparoscopic Surgery (FLS) technical and cognitive examination became a mandatory prerequisite for the American Board of Surgery (ABS) qualification examination in general surgery in 2010. The Fundamentals of Endoscopic Surgery (FES) became a prerequisite to ABS qualification in 2015. In the future, institutions may require simulator
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Surgery_Schwartz. surgeryLaparoscopic surgerySeamless surgeryProgress in surgeryfor all surgeons. This technology has the advantage of enabling objective measurement of psychomotor skills, which can be used to determine progress in skill acquisition and, ultimately, techni-cal competency.101 Several of these devices have been validated as a means of measuring proficiency in skill performance. More importantly, training on virtual reality platforms has proven to translate to improved operative performance in randomized tri-als.102,103 Currently, surgical skills labs are mandatory for Resi-dency Review Committee credentialing. Successful completion of the Fundamentals of Laparoscopic Surgery (FLS) technical and cognitive examination became a mandatory prerequisite for the American Board of Surgery (ABS) qualification examination in general surgery in 2010. The Fundamentals of Endoscopic Surgery (FES) became a prerequisite to ABS qualification in 2015. In the future, institutions may require simulator
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Surgery_Schwartz_3232
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examination in general surgery in 2010. The Fundamentals of Endoscopic Surgery (FES) became a prerequisite to ABS qualification in 2015. In the future, institutions may require simulator training to document specific entrustable professional activities (EPA) related to laparoscopic procedures before privileging in the OR. A Fundamentals of Robotic Surgery (FRS) high stakes exam is on the horizon for future surgical trainees. The American Col-lege of Surgeons has taken a leadership position in accrediting skills labs across the world as American College of Surgeons–accredited educational institutes.TelementoringIn response to the Institute of Medicine’s call for the develop-ment of unique technologic solutions to deliver health care to rural and underserved areas, surgeons are beginning to explore the feasibility of telementoring. Teleconsultation or telemen-toring is two-way audio and visual communication between two geographically separated providers. This communication can take
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Surgery_Schwartz. examination in general surgery in 2010. The Fundamentals of Endoscopic Surgery (FES) became a prerequisite to ABS qualification in 2015. In the future, institutions may require simulator training to document specific entrustable professional activities (EPA) related to laparoscopic procedures before privileging in the OR. A Fundamentals of Robotic Surgery (FRS) high stakes exam is on the horizon for future surgical trainees. The American Col-lege of Surgeons has taken a leadership position in accrediting skills labs across the world as American College of Surgeons–accredited educational institutes.TelementoringIn response to the Institute of Medicine’s call for the develop-ment of unique technologic solutions to deliver health care to rural and underserved areas, surgeons are beginning to explore the feasibility of telementoring. Teleconsultation or telemen-toring is two-way audio and visual communication between two geographically separated providers. This communication can take
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to explore the feasibility of telementoring. Teleconsultation or telemen-toring is two-way audio and visual communication between two geographically separated providers. This communication can take place in the office setting or directly in the OR when complex scenarios are encountered. Although local commu-nication channels may limit its performance in rural areas, the technology is available and currently is being used, espe-cially in states and provinces with large geographically remote populations.103Innovation and Introduction of New ProceduresThe revolution in minimally invasive general surgery, which occurred in 1990, created ethical challenges for the profession. The problem was this: If competence is gained from experience, how was the surgeon to climb the competence curve (otherwise known as the learning curve) without injuring patients? If it was indeed impossible to achieve competence without making mis-takes along the way, how should one effectively communicate this to
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Surgery_Schwartz. to explore the feasibility of telementoring. Teleconsultation or telemen-toring is two-way audio and visual communication between two geographically separated providers. This communication can take place in the office setting or directly in the OR when complex scenarios are encountered. Although local commu-nication channels may limit its performance in rural areas, the technology is available and currently is being used, espe-cially in states and provinces with large geographically remote populations.103Innovation and Introduction of New ProceduresThe revolution in minimally invasive general surgery, which occurred in 1990, created ethical challenges for the profession. The problem was this: If competence is gained from experience, how was the surgeon to climb the competence curve (otherwise known as the learning curve) without injuring patients? If it was indeed impossible to achieve competence without making mis-takes along the way, how should one effectively communicate this to
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known as the learning curve) without injuring patients? If it was indeed impossible to achieve competence without making mis-takes along the way, how should one effectively communicate this to patients such that they understand the weight of their decisions? Even more fundamentally important is determining the path that should be followed before one recruits the first patient for a new procedure.Although procedure development is fundamentally dif-ferent than drug development (i.e., there is great individual variation in the performance of procedures, but no difference between one tablet and the next), adherence to a process simi-lar to that used to develop a new drug is a reasonable path for a surgical innovator. At the outset, the surgeon must iden-tify the problem that is not solved with current surgical pro-cedures. For example, although the removal of a gallbladder through a Kocher incision is certainly effective, it creates a great deal of disability, pain, and scarification. As
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Surgery_Schwartz. known as the learning curve) without injuring patients? If it was indeed impossible to achieve competence without making mis-takes along the way, how should one effectively communicate this to patients such that they understand the weight of their decisions? Even more fundamentally important is determining the path that should be followed before one recruits the first patient for a new procedure.Although procedure development is fundamentally dif-ferent than drug development (i.e., there is great individual variation in the performance of procedures, but no difference between one tablet and the next), adherence to a process simi-lar to that used to develop a new drug is a reasonable path for a surgical innovator. At the outset, the surgeon must iden-tify the problem that is not solved with current surgical pro-cedures. For example, although the removal of a gallbladder through a Kocher incision is certainly effective, it creates a great deal of disability, pain, and scarification. As
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current surgical pro-cedures. For example, although the removal of a gallbladder through a Kocher incision is certainly effective, it creates a great deal of disability, pain, and scarification. As a result of those issues, many patients with very symptomatic biliary colic delayed operation until life-threatening complications occurred. Clearly, there was a need for developing a less inva-sive approach (Fig. 14-30).Once the opportunity has been established, the next step involves a search through other disciplines for technologies and techniques that might be applied. Again, this is analogous to the drug industry, where secondary drug indications have often turned out to be more therapeutically important than the primary indication for drug development. The third step is in vivo stud-ies in the most appropriate animal model. These types of studies are controversial because of the resistance to animal experimen-tation, and yet without such studies, many humans would be injured or
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Surgery_Schwartz. current surgical pro-cedures. For example, although the removal of a gallbladder through a Kocher incision is certainly effective, it creates a great deal of disability, pain, and scarification. As a result of those issues, many patients with very symptomatic biliary colic delayed operation until life-threatening complications occurred. Clearly, there was a need for developing a less inva-sive approach (Fig. 14-30).Once the opportunity has been established, the next step involves a search through other disciplines for technologies and techniques that might be applied. Again, this is analogous to the drug industry, where secondary drug indications have often turned out to be more therapeutically important than the primary indication for drug development. The third step is in vivo stud-ies in the most appropriate animal model. These types of studies are controversial because of the resistance to animal experimen-tation, and yet without such studies, many humans would be injured or
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in the most appropriate animal model. These types of studies are controversial because of the resistance to animal experimen-tation, and yet without such studies, many humans would be injured or killed during the developmental phase of medical drugs, devices, and techniques. These steps often are called the preclinical phase of procedure development.The decision as to when such procedures are ready to come out of the lab is a difficult one. Put simply, the proce-dure should be reproducible, provide the desired effect, and not have serious side effects. Once these three criteria are reached, the time for human application has arrived. Before the surgeon discusses the new procedure with patients, it is important to achieve full institutional support. Involvement of the medi-cal board, the chief of the medical staff, and the institutional review board is essential before commencing on a new proce-dure. These bodies are responsible for the use of safe, high-quality medical practices
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Surgery_Schwartz. in the most appropriate animal model. These types of studies are controversial because of the resistance to animal experimen-tation, and yet without such studies, many humans would be injured or killed during the developmental phase of medical drugs, devices, and techniques. These steps often are called the preclinical phase of procedure development.The decision as to when such procedures are ready to come out of the lab is a difficult one. Put simply, the proce-dure should be reproducible, provide the desired effect, and not have serious side effects. Once these three criteria are reached, the time for human application has arrived. Before the surgeon discusses the new procedure with patients, it is important to achieve full institutional support. Involvement of the medi-cal board, the chief of the medical staff, and the institutional review board is essential before commencing on a new proce-dure. These bodies are responsible for the use of safe, high-quality medical practices
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the chief of the medical staff, and the institutional review board is essential before commencing on a new proce-dure. These bodies are responsible for the use of safe, high-quality medical practices within their institution, and they will demand that great caution and all possible safeguards are in place before proceeding.The dialogue with the patient who is to be first must be thorough, brutally honest, and well documented. The psychology Brunicardi_Ch14_p0453-p0478.indd 47501/03/19 4:59 PM 476BASIC CONSIDERATIONSPART Ithat allows a patient to decide to be first is quite interesting, and may, under certain circumstances, require psychiatric evalua-tion. Certainly, if a dying cancer patient has a chance with a new drug, this makes sense. Similarly, if the standard surgical procedure has a high attendant morbidity and the new procedure offers a substantially better outcome, the decision to be first is understandable. On the other hand, when the benefits of the new approach are
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Surgery_Schwartz. the chief of the medical staff, and the institutional review board is essential before commencing on a new proce-dure. These bodies are responsible for the use of safe, high-quality medical practices within their institution, and they will demand that great caution and all possible safeguards are in place before proceeding.The dialogue with the patient who is to be first must be thorough, brutally honest, and well documented. The psychology Brunicardi_Ch14_p0453-p0478.indd 47501/03/19 4:59 PM 476BASIC CONSIDERATIONSPART Ithat allows a patient to decide to be first is quite interesting, and may, under certain circumstances, require psychiatric evalua-tion. Certainly, if a dying cancer patient has a chance with a new drug, this makes sense. Similarly, if the standard surgical procedure has a high attendant morbidity and the new procedure offers a substantially better outcome, the decision to be first is understandable. On the other hand, when the benefits of the new approach are
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has a high attendant morbidity and the new procedure offers a substantially better outcome, the decision to be first is understandable. On the other hand, when the benefits of the new approach are small and the risks are largely unknown, a more complete psychological profile may be necessary before proceeding.For new surgical procedures, it generally is wise to assemble the best possible operative team, including a surgeon experienced with the old technique, and assistants who have participated in the earlier animal work. This initial team of experienced physicians and nurses should remain together until full competence with the procedure is attained. This may take 10 procedures, or it may take 50 procedures. The team will know that it has achieved competence when the majority of procedures take the same length of time and the team is relaxed and sure of the flow of the operation. This will complete phase I of the procedure development.In phase II, the efficacy of the procedure is
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Surgery_Schwartz. has a high attendant morbidity and the new procedure offers a substantially better outcome, the decision to be first is understandable. On the other hand, when the benefits of the new approach are small and the risks are largely unknown, a more complete psychological profile may be necessary before proceeding.For new surgical procedures, it generally is wise to assemble the best possible operative team, including a surgeon experienced with the old technique, and assistants who have participated in the earlier animal work. This initial team of experienced physicians and nurses should remain together until full competence with the procedure is attained. This may take 10 procedures, or it may take 50 procedures. The team will know that it has achieved competence when the majority of procedures take the same length of time and the team is relaxed and sure of the flow of the operation. This will complete phase I of the procedure development.In phase II, the efficacy of the procedure is
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take the same length of time and the team is relaxed and sure of the flow of the operation. This will complete phase I of the procedure development.In phase II, the efficacy of the procedure is tested in a nonrandomized fashion. Ideally, the outcome of new techniques must be as good as or better than the procedure that is being replaced. This phase should occur at several medical centers to prove that good outcomes are achievable outside of the pioneer-ing institution. These same requirements may be applied to the introduction of new technology into the OR. The value equation requires that the additional measurable procedure quality exceeds the additional measurable cost to the patient or healthcare system. In phase III, a randomized trial pits the new procedure against the old.Once the competence curve has been climbed, it is appro-priate for the team to engage in the education of others. Dur-ing the ascension of the competence curve, other learners in the institution (i.e., surgical
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Surgery_Schwartz. take the same length of time and the team is relaxed and sure of the flow of the operation. This will complete phase I of the procedure development.In phase II, the efficacy of the procedure is tested in a nonrandomized fashion. Ideally, the outcome of new techniques must be as good as or better than the procedure that is being replaced. This phase should occur at several medical centers to prove that good outcomes are achievable outside of the pioneer-ing institution. These same requirements may be applied to the introduction of new technology into the OR. The value equation requires that the additional measurable procedure quality exceeds the additional measurable cost to the patient or healthcare system. In phase III, a randomized trial pits the new procedure against the old.Once the competence curve has been climbed, it is appro-priate for the team to engage in the education of others. Dur-ing the ascension of the competence curve, other learners in the institution (i.e., surgical
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curve has been climbed, it is appro-priate for the team to engage in the education of others. Dur-ing the ascension of the competence curve, other learners in the institution (i.e., surgical residents) may not have the opportunity to participate in the first case series. Although this may be dif-ficult for them, the best interest of the patient must be put before the education of the resident.The second stage of learning occurs when the new pro-cedure has proven its value and a handful of experts exist, but the majority of surgeons have not been trained to perform the new procedure. In this setting, it is relatively unethical for sur-geons to forge ahead with a new procedure in humans as if they had spent the same amount of time in intensive study that the first team did. The fact that one or several surgical teams were able to perform an operation does not ensure that all others with the same medical degrees can perform the operation with equal skill. It behooves the learners to
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Surgery_Schwartz. curve has been climbed, it is appro-priate for the team to engage in the education of others. Dur-ing the ascension of the competence curve, other learners in the institution (i.e., surgical residents) may not have the opportunity to participate in the first case series. Although this may be dif-ficult for them, the best interest of the patient must be put before the education of the resident.The second stage of learning occurs when the new pro-cedure has proven its value and a handful of experts exist, but the majority of surgeons have not been trained to perform the new procedure. In this setting, it is relatively unethical for sur-geons to forge ahead with a new procedure in humans as if they had spent the same amount of time in intensive study that the first team did. The fact that one or several surgical teams were able to perform an operation does not ensure that all others with the same medical degrees can perform the operation with equal skill. It behooves the learners to
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one or several surgical teams were able to perform an operation does not ensure that all others with the same medical degrees can perform the operation with equal skill. It behooves the learners to contact the experts and request their assistance to ensure an optimal outcome at the new center. Although it is important that the learners contact the experts, it is equally important that the experts be willing to share their experience with their fellow professionals. As well, the experts should provide feedback to the learners as to whether they feel the learners are equipped to forge ahead on their own. If not, further observation and assistance from the experts are required. Although this approach may sound obvious, it is fraught with difficulties. In many situations, ego, competitiveness, and mon-etary concerns have short-circuited this process and led to poor patient outcomes. To a large extent, MIS has recovered from the black eye it received early in development, when inadequately
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Surgery_Schwartz. one or several surgical teams were able to perform an operation does not ensure that all others with the same medical degrees can perform the operation with equal skill. It behooves the learners to contact the experts and request their assistance to ensure an optimal outcome at the new center. Although it is important that the learners contact the experts, it is equally important that the experts be willing to share their experience with their fellow professionals. As well, the experts should provide feedback to the learners as to whether they feel the learners are equipped to forge ahead on their own. If not, further observation and assistance from the experts are required. Although this approach may sound obvious, it is fraught with difficulties. In many situations, ego, competitiveness, and mon-etary concerns have short-circuited this process and led to poor patient outcomes. To a large extent, MIS has recovered from the black eye it received early in development, when inadequately
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and mon-etary concerns have short-circuited this process and led to poor patient outcomes. To a large extent, MIS has recovered from the black eye it received early in development, when inadequately trained surgeons caused an excessive number of significant complications.If innovative procedures and technologies are to be devel-oped and applied without the mistakes of the past, surgeons must be honest when they answer these questions: Is this procedure safe? Would I consider undergoing this procedure if I developed a surgical indication? Is the procedure as good as or better than the procedure it is replacing? Do I have the skills to apply this procedure safely and with equivalent results to the more expe-rienced surgeon? Answering these questions in the affirmative should be a professional obligation. A negative response should motivate the surgeon to seek an alternative procedure or outside assistance before subjecting a patient to the new procedure.REFERENCESEntries highlighted in
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Surgery_Schwartz. and mon-etary concerns have short-circuited this process and led to poor patient outcomes. To a large extent, MIS has recovered from the black eye it received early in development, when inadequately trained surgeons caused an excessive number of significant complications.If innovative procedures and technologies are to be devel-oped and applied without the mistakes of the past, surgeons must be honest when they answer these questions: Is this procedure safe? Would I consider undergoing this procedure if I developed a surgical indication? Is the procedure as good as or better than the procedure it is replacing? Do I have the skills to apply this procedure safely and with equivalent results to the more expe-rienced surgeon? Answering these questions in the affirmative should be a professional obligation. A negative response should motivate the surgeon to seek an alternative procedure or outside assistance before subjecting a patient to the new procedure.REFERENCESEntries highlighted in
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obligation. A negative response should motivate the surgeon to seek an alternative procedure or outside assistance before subjecting a patient to the new procedure.REFERENCESEntries highlighted in bright blue are key references. 1. Hopkins HH. Optical principles of the endoscope. In: Berci G, ed. Endoscopy. New York: Appleton-Century-Crofts; 1976:3-27. 2. Katzir A. Optical fibers in medicine. Sci Am. 1989;260:120-125. 3. Hirschowitz BI. A personal history of the fiberscope. Gastro-enterology. 1979;76:864-869. 4. Veritas TF. Coelioscopy: a synthesis of Georg Kelling’s work with insufflation, endoscopy, and luft tamponade. In: Litynski GS, ed. Highlights in the History of Laparoscopy. Frankfurt/Main: Barbara Bernert Verlag; 1996:3. 5. Ponsky JL, Gauderer MW. Percutaneous endoscopic gastros-tomy: a nonoperative technique for feeding gastrostomy. Gastrointest Endosc. 1981;27:9-11. 6. Lehman KS, Ritz JP, Wibmer A, et al. The German registry for natural orifice translumenal endoscopic
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Surgery_Schwartz. obligation. A negative response should motivate the surgeon to seek an alternative procedure or outside assistance before subjecting a patient to the new procedure.REFERENCESEntries highlighted in bright blue are key references. 1. Hopkins HH. Optical principles of the endoscope. In: Berci G, ed. Endoscopy. New York: Appleton-Century-Crofts; 1976:3-27. 2. Katzir A. Optical fibers in medicine. Sci Am. 1989;260:120-125. 3. Hirschowitz BI. A personal history of the fiberscope. Gastro-enterology. 1979;76:864-869. 4. Veritas TF. Coelioscopy: a synthesis of Georg Kelling’s work with insufflation, endoscopy, and luft tamponade. In: Litynski GS, ed. Highlights in the History of Laparoscopy. Frankfurt/Main: Barbara Bernert Verlag; 1996:3. 5. Ponsky JL, Gauderer MW. Percutaneous endoscopic gastros-tomy: a nonoperative technique for feeding gastrostomy. Gastrointest Endosc. 1981;27:9-11. 6. Lehman KS, Ritz JP, Wibmer A, et al. The German registry for natural orifice translumenal endoscopic
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a nonoperative technique for feeding gastrostomy. Gastrointest Endosc. 1981;27:9-11. 6. Lehman KS, Ritz JP, Wibmer A, et al. The German registry for natural orifice translumenal endoscopic surgery: the report of the first 551 patients. Ann Surg. 2010;252(2):263-270. 7. Autorino R, White WM, Gettman MT, et al. Public percep-tion of “scarless” surgery: a critical analysis of the litera-ture. Urology. 2012;80(3):495-502. 8. Ahmed I, Ciancio F, Ferrar V, et al. Current status of single-incision laparoscopic surgery: European experts’ views. Surg Laparosc Endosc Percutan Tech. 2012;22(3):194-199. 9. Wood BJ, Ramkaransingh JR, Fogo T, Walther MM, Libutti SK. Percutaneous tumor ablation with radiofrequency. Cancer. 2002;94(2):443-451. 10. Smith RS, Fry WR, Tsoi EK, et al. Gasless laparoscopy and conventional instruments: the next phase of minimally inva-sive surgery. Arch Surg. 1993;128(10):1102-1107. 11. Litynski GS. Highlights in the History of Laparoscopy. Frankfurt/Main: Barbara Bernert
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Surgery_Schwartz. a nonoperative technique for feeding gastrostomy. Gastrointest Endosc. 1981;27:9-11. 6. Lehman KS, Ritz JP, Wibmer A, et al. The German registry for natural orifice translumenal endoscopic surgery: the report of the first 551 patients. Ann Surg. 2010;252(2):263-270. 7. Autorino R, White WM, Gettman MT, et al. Public percep-tion of “scarless” surgery: a critical analysis of the litera-ture. Urology. 2012;80(3):495-502. 8. Ahmed I, Ciancio F, Ferrar V, et al. Current status of single-incision laparoscopic surgery: European experts’ views. Surg Laparosc Endosc Percutan Tech. 2012;22(3):194-199. 9. Wood BJ, Ramkaransingh JR, Fogo T, Walther MM, Libutti SK. Percutaneous tumor ablation with radiofrequency. Cancer. 2002;94(2):443-451. 10. Smith RS, Fry WR, Tsoi EK, et al. Gasless laparoscopy and conventional instruments: the next phase of minimally inva-sive surgery. Arch Surg. 1993;128(10):1102-1107. 11. Litynski GS. Highlights in the History of Laparoscopy. Frankfurt/Main: Barbara Bernert
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conventional instruments: the next phase of minimally inva-sive surgery. Arch Surg. 1993;128(10):1102-1107. 11. Litynski GS. Highlights in the History of Laparoscopy. Frankfurt/Main: Barbara Bernert Verlag; 1996:78. 12. Hunter JG, Staheli J, Oddsdottir M, Trus T. Nitrous oxide pneumoperitoneum revisited: is there a risk of combustion? Surg Endosc. 1995;9(5):501-504. 13. Tsereteli Z, Terry ML, Bowers S, et al. Prospective random-ized clinical trial comparing nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic surgery. J Am Coll Surg. 2002;195(2):173-179. 14. Callery MP, Soper NJ. Physiology of the pneumoperito-neum. In: Hunter JG, ed. Baillière’s Clinical Gastroenterol-ogy: Laparoscopic Surgery. London/Philadelphia: Baillière Tindall; 1993:757. 15. Ho HS, Gunther RA, Wolfe B. Intraperitoneal carbon diox-ide insufflation and cardiopulmonary functions. Arch Surg. 1992;127(8):928-932. 16. Wittgen CM, Andrus CH, Fitzgerald S, Baudendistel LJ, Dahms TE, Kaminski DL. Analysis
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Surgery_Schwartz. conventional instruments: the next phase of minimally inva-sive surgery. Arch Surg. 1993;128(10):1102-1107. 11. Litynski GS. Highlights in the History of Laparoscopy. Frankfurt/Main: Barbara Bernert Verlag; 1996:78. 12. Hunter JG, Staheli J, Oddsdottir M, Trus T. Nitrous oxide pneumoperitoneum revisited: is there a risk of combustion? Surg Endosc. 1995;9(5):501-504. 13. Tsereteli Z, Terry ML, Bowers S, et al. Prospective random-ized clinical trial comparing nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic surgery. J Am Coll Surg. 2002;195(2):173-179. 14. Callery MP, Soper NJ. Physiology of the pneumoperito-neum. In: Hunter JG, ed. Baillière’s Clinical Gastroenterol-ogy: Laparoscopic Surgery. London/Philadelphia: Baillière Tindall; 1993:757. 15. Ho HS, Gunther RA, Wolfe B. Intraperitoneal carbon diox-ide insufflation and cardiopulmonary functions. Arch Surg. 1992;127(8):928-932. 16. Wittgen CM, Andrus CH, Fitzgerald S, Baudendistel LJ, Dahms TE, Kaminski DL. Analysis
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Intraperitoneal carbon diox-ide insufflation and cardiopulmonary functions. Arch Surg. 1992;127(8):928-932. 16. Wittgen CM, Andrus CH, Fitzgerald S, Baudendistel LJ, Dahms TE, Kaminski DL. Analysis of the hemodynamic and ventilatory effects of laparoscopic cholecystectomy. Arch Surg. 1991;126(8):997-1000. 17. Cullen DJ, Eger EI. Cardiovascular effects of carbon dioxide in man. Anesthesiology. 1974;41(4):345-349. 18. Cunningham AJ, Turner J, Rosenbaum S, et al. Transoesopha-geal echocardiographic assessment of haemodynamic func-tion during laparoscopic cholecystectomy. Br J Anaesth. 1993;70(6):621-625.8Brunicardi_Ch14_p0453-p0478.indd 47601/03/19 4:59 PM 477MINIMALLY INVASIVE SURGERYCHAPTER 14 19. Harris MNE, Plantevin OM, Crowther A, et al. Cardiac arrhythmias during anaesthesia for laparoscopy. Br J Anaesth. 1984;56(11):1213-1217. 20. Borten M, Friedman EA. Choice of anaesthesia. In: Laparo-scopic Complications: Prevention and Management. Toronto: BC Decker;
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Surgery_Schwartz. Intraperitoneal carbon diox-ide insufflation and cardiopulmonary functions. Arch Surg. 1992;127(8):928-932. 16. Wittgen CM, Andrus CH, Fitzgerald S, Baudendistel LJ, Dahms TE, Kaminski DL. Analysis of the hemodynamic and ventilatory effects of laparoscopic cholecystectomy. Arch Surg. 1991;126(8):997-1000. 17. Cullen DJ, Eger EI. Cardiovascular effects of carbon dioxide in man. Anesthesiology. 1974;41(4):345-349. 18. Cunningham AJ, Turner J, Rosenbaum S, et al. Transoesopha-geal echocardiographic assessment of haemodynamic func-tion during laparoscopic cholecystectomy. Br J Anaesth. 1993;70(6):621-625.8Brunicardi_Ch14_p0453-p0478.indd 47601/03/19 4:59 PM 477MINIMALLY INVASIVE SURGERYCHAPTER 14 19. Harris MNE, Plantevin OM, Crowther A, et al. Cardiac arrhythmias during anaesthesia for laparoscopy. Br J Anaesth. 1984;56(11):1213-1217. 20. Borten M, Friedman EA. Choice of anaesthesia. In: Laparo-scopic Complications: Prevention and Management. Toronto: BC Decker;
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anaesthesia for laparoscopy. Br J Anaesth. 1984;56(11):1213-1217. 20. Borten M, Friedman EA. Choice of anaesthesia. In: Laparo-scopic Complications: Prevention and Management. Toronto: BC Decker; 1986:173. 21. Jorgenson JO, Hanel K, Lalak NJ, Hunt Dr, North L, Morris DL. Thromboembolic complications of laparoscopic cholecys-tectomy (letter). Br Med J. 1993;306:518-519. 22. Ho HS, Wolfe BM. The physiology and immunology of endo-surgery. In: Toouli JG, Gossot D, Hunter JG, eds. Endosur-gery. New York/London: Churchill-Livingstone; 1996:163. 23. Sackier JM, Nibhanupudy B. The pneumoperitoneumphysiology and complications. In: Toouli JG, Gossot D, Hunter JG, eds. Endosurgery. New York/London: Churchill-Livingstone; 1996:155. 24. Kashtan J, Green JF, Parsons EQ, Holcroft JW. Hemody-namic effects of increased abdominal pressure. J Surg Res. 1981;30(3):249-255. 25. McDougall EM, Monk TG, Wolf JS Jr, et al. The effect of prolonged pneumoperitoneum on renal function in an animal model. J Am
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Surgery_Schwartz. anaesthesia for laparoscopy. Br J Anaesth. 1984;56(11):1213-1217. 20. Borten M, Friedman EA. Choice of anaesthesia. In: Laparo-scopic Complications: Prevention and Management. Toronto: BC Decker; 1986:173. 21. Jorgenson JO, Hanel K, Lalak NJ, Hunt Dr, North L, Morris DL. Thromboembolic complications of laparoscopic cholecys-tectomy (letter). Br Med J. 1993;306:518-519. 22. Ho HS, Wolfe BM. The physiology and immunology of endo-surgery. In: Toouli JG, Gossot D, Hunter JG, eds. Endosur-gery. New York/London: Churchill-Livingstone; 1996:163. 23. Sackier JM, Nibhanupudy B. The pneumoperitoneumphysiology and complications. In: Toouli JG, Gossot D, Hunter JG, eds. Endosurgery. New York/London: Churchill-Livingstone; 1996:155. 24. Kashtan J, Green JF, Parsons EQ, Holcroft JW. Hemody-namic effects of increased abdominal pressure. J Surg Res. 1981;30(3):249-255. 25. McDougall EM, Monk TG, Wolf JS Jr, et al. The effect of prolonged pneumoperitoneum on renal function in an animal model. J Am
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of increased abdominal pressure. J Surg Res. 1981;30(3):249-255. 25. McDougall EM, Monk TG, Wolf JS Jr, et al. The effect of prolonged pneumoperitoneum on renal function in an animal model. J Am Coll Surg. 1996;182(4):317-328. 26. Lindberg F, Bergqvist D, Bjorck M, Rasmussen I. Renal hemodynamics during carbon dioxide pneumoperitoneum: an experimental study in pigs. Surg Endosc. 2003;17(3): 480-484. 27. Hazebroek EJ, de Vos tot Nederveen Cappel R, Gommers D, et al. Antidiuretic hormone release during laparoscopic donor nephrectomy. Arch Surg. 2002;137(5):600-604; discussion 605. 28. Ostman PL, Pantle-Fisher FH, Fanre EA, Glosten B. Circula-tory collapse during laparoscopy. J Clin Anesth. 1990;2(2): 129-132. 29. Alijani A, Cuschieri A. Abdominal wall lift systems in lapa-roscopic surgery: gasless and low-pressure systems. Semin Laparosc Surg. 2001;8(1):53-62. 30. Ozawa A, Konishi F, Nagai H, Okada M, Kanazawa K. Cytokine and hormonal responses in laparoscopic-assisted colectomy and
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Surgery_Schwartz. of increased abdominal pressure. J Surg Res. 1981;30(3):249-255. 25. McDougall EM, Monk TG, Wolf JS Jr, et al. The effect of prolonged pneumoperitoneum on renal function in an animal model. J Am Coll Surg. 1996;182(4):317-328. 26. Lindberg F, Bergqvist D, Bjorck M, Rasmussen I. Renal hemodynamics during carbon dioxide pneumoperitoneum: an experimental study in pigs. Surg Endosc. 2003;17(3): 480-484. 27. Hazebroek EJ, de Vos tot Nederveen Cappel R, Gommers D, et al. Antidiuretic hormone release during laparoscopic donor nephrectomy. Arch Surg. 2002;137(5):600-604; discussion 605. 28. Ostman PL, Pantle-Fisher FH, Fanre EA, Glosten B. Circula-tory collapse during laparoscopy. J Clin Anesth. 1990;2(2): 129-132. 29. Alijani A, Cuschieri A. Abdominal wall lift systems in lapa-roscopic surgery: gasless and low-pressure systems. Semin Laparosc Surg. 2001;8(1):53-62. 30. Ozawa A, Konishi F, Nagai H, Okada M, Kanazawa K. Cytokine and hormonal responses in laparoscopic-assisted colectomy and
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gasless and low-pressure systems. Semin Laparosc Surg. 2001;8(1):53-62. 30. Ozawa A, Konishi F, Nagai H, Okada M, Kanazawa K. Cytokine and hormonal responses in laparoscopic-assisted colectomy and conventional open colectomy. Surg Today. 2000;30(2):107-111. 31. Burpee SE, Kurian M, Murakame Y, Benevides S, Gagner M. The metabolic and immune response to laparoscopic versus open liver resection. Surg Endosc. 2002;16(6):899-904. 32. Gossot D. Access modalities for thoracoscopic surgery. In: Toouli JG, Gossot D, Hunter JG, eds. Endosurgery. New York/London: Churchill-Livingstone; 1996:743. 33. Memon MA, Cooper NJ, Memon B, Memon MI, Abrams KR. Meta-analysis of randomized clinical trials compar-ing open and laparoscopic inguinal hernia repair. Br J Surg. 2003;90(12):1479-1492. 34. Himpens J. Laparoscopic preperitoneal approach to the ingui-nal hernia. In: Toouli JG, Gossot D, Hunter JG, eds. Endosur-gery. New York/London: Churchill-Livingstone; 1996:949. 35. Horvath KD, Kao LS, Wherry KL,
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Surgery_Schwartz. gasless and low-pressure systems. Semin Laparosc Surg. 2001;8(1):53-62. 30. Ozawa A, Konishi F, Nagai H, Okada M, Kanazawa K. Cytokine and hormonal responses in laparoscopic-assisted colectomy and conventional open colectomy. Surg Today. 2000;30(2):107-111. 31. Burpee SE, Kurian M, Murakame Y, Benevides S, Gagner M. The metabolic and immune response to laparoscopic versus open liver resection. Surg Endosc. 2002;16(6):899-904. 32. Gossot D. Access modalities for thoracoscopic surgery. In: Toouli JG, Gossot D, Hunter JG, eds. Endosurgery. New York/London: Churchill-Livingstone; 1996:743. 33. Memon MA, Cooper NJ, Memon B, Memon MI, Abrams KR. Meta-analysis of randomized clinical trials compar-ing open and laparoscopic inguinal hernia repair. Br J Surg. 2003;90(12):1479-1492. 34. Himpens J. Laparoscopic preperitoneal approach to the ingui-nal hernia. In: Toouli JG, Gossot D, Hunter JG, eds. Endosur-gery. New York/London: Churchill-Livingstone; 1996:949. 35. Horvath KD, Kao LS, Wherry KL,
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preperitoneal approach to the ingui-nal hernia. In: Toouli JG, Gossot D, Hunter JG, eds. Endosur-gery. New York/London: Churchill-Livingstone; 1996:949. 35. Horvath KD, Kao LS, Wherry KL, Pellegrini CA, Sinanan MN. A technique for laparoscopic-assisted percutaneous drainage of infected pancreatic necrosis and pancreatic abscess. Surg Endosc. 2001;15(10):1221-1225. 36. Eaves FF. Basics of endoscopic plastic surgery. In: Bostwick J, Eaves FF, Nahai F, eds. Endoscopic Plastic Surgery. St Louis: Quality Medical Publishing; 1995:59. 37. Kenyon TA, Lenker MP, Bax TW, Swanström LL. Cost and benefit of the trained laparoscopic team. A comparative study of a designated nursing team vs. a nontrained team. Surg Endosc. 1997;11(8):812-814. 38. Herron DM, Gagner M, Kenyon TL, Swanström LL. The mini-mally invasive surgical suite enters the 21st century. A discussion of critical design elements. Surg Endosc. 2001;15(4):415-422. 39. Byron JW, Markenson G, Miyazawa K. A randomised com-parison of
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Surgery_Schwartz. preperitoneal approach to the ingui-nal hernia. In: Toouli JG, Gossot D, Hunter JG, eds. Endosur-gery. New York/London: Churchill-Livingstone; 1996:949. 35. Horvath KD, Kao LS, Wherry KL, Pellegrini CA, Sinanan MN. A technique for laparoscopic-assisted percutaneous drainage of infected pancreatic necrosis and pancreatic abscess. Surg Endosc. 2001;15(10):1221-1225. 36. Eaves FF. Basics of endoscopic plastic surgery. In: Bostwick J, Eaves FF, Nahai F, eds. Endoscopic Plastic Surgery. St Louis: Quality Medical Publishing; 1995:59. 37. Kenyon TA, Lenker MP, Bax TW, Swanström LL. Cost and benefit of the trained laparoscopic team. A comparative study of a designated nursing team vs. a nontrained team. Surg Endosc. 1997;11(8):812-814. 38. Herron DM, Gagner M, Kenyon TL, Swanström LL. The mini-mally invasive surgical suite enters the 21st century. A discussion of critical design elements. Surg Endosc. 2001;15(4):415-422. 39. Byron JW, Markenson G, Miyazawa K. A randomised com-parison of
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invasive surgical suite enters the 21st century. A discussion of critical design elements. Surg Endosc. 2001;15(4):415-422. 39. Byron JW, Markenson G, Miyazawa K. A randomised com-parison of Veress needle and direct insertion for laparoscopy. Surg Gynecol Obstet. 1993;177(3):259-262. 40. Fletcher DR. Laparoscopic access. In: Toouli JG, Gossot D, Hunter JG, eds. Endosurgery. New York/London: Churchill-Livingstone; 1996:189. 41. Hanney RM, Alle KM, Cregan PC. Major vascular injury and laparoscopy. Aust N Z J Surg. 1995;65(7):533-535. 42. Catarci M, Carlini M, Gentileschi P, Santoro E. Major and minor injuries during the creation of pneumoperito-neum. A multicenter study on 12,919 cases. Surg Endosc. 2001;15(6):566-569. 43. Siperstein AE, Berber E, Engle KL, Duh QY, Clark OH. Lap-aroscopic posterior adrenalectomy: technical considerations. Arch Surg. 2000;135(8):967-971. 44. Vasilev SA, McGonigle KF. Extraperitoneal laparo-scopic para-aortic lymph node dissection. Gynecol Oncol.
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et al. Mini-mally invasive esophagectomy: outcomes in 222 patients. Ann Surg. 2003;238(4):486-494; discussion 494. 97. Fleshman J, Sargent DJ, Green E, for the Clinical Out-comes of Surgical Therapy Study Group. Laparoscopic col-ectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial. Ann Surg. 2007;246(4):655-662; discussion 662. 98. Fried GM, Clas D, Meakins JL. Minimally invasive surgery in the elderly patient. Surg Clin North Am. 1994;74(2):375-387. 99. Borman PC, Terblanche J. Subtotal cholecystectomy: for the difficult gallbladder in portal hypertension and cholecystitis. Surgery. 1985;98(1):1-6. 100. Litwin DWM, Pham Q. Laparoscopic surgery in the compli-cated patient. In: Eubanks WS, Swanstrom LJ, Soper NJ, eds. Mastery of Endoscopic and Laparoscopic Surgery. Philadelphia: Lippincott, Williams & Wilkins; 2000:57. 101. Gallagher AG, Smith CD, Bowers SP, et al. Psychomotor skills assessment in practicing surgeons experienced in
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Surgery_Schwartz. et al. Mini-mally invasive esophagectomy: outcomes in 222 patients. Ann Surg. 2003;238(4):486-494; discussion 494. 97. Fleshman J, Sargent DJ, Green E, for the Clinical Out-comes of Surgical Therapy Study Group. Laparoscopic col-ectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial. Ann Surg. 2007;246(4):655-662; discussion 662. 98. Fried GM, Clas D, Meakins JL. Minimally invasive surgery in the elderly patient. Surg Clin North Am. 1994;74(2):375-387. 99. Borman PC, Terblanche J. Subtotal cholecystectomy: for the difficult gallbladder in portal hypertension and cholecystitis. Surgery. 1985;98(1):1-6. 100. Litwin DWM, Pham Q. Laparoscopic surgery in the compli-cated patient. In: Eubanks WS, Swanstrom LJ, Soper NJ, eds. Mastery of Endoscopic and Laparoscopic Surgery. Philadelphia: Lippincott, Williams & Wilkins; 2000:57. 101. Gallagher AG, Smith CD, Bowers SP, et al. Psychomotor skills assessment in practicing surgeons experienced in
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and Laparoscopic Surgery. Philadelphia: Lippincott, Williams & Wilkins; 2000:57. 101. Gallagher AG, Smith CD, Bowers SP, et al. Psychomotor skills assessment in practicing surgeons experienced in per-forming advanced laparoscopic procedures. J Am Coll Surg. 2003;197(3):479-488. 102. Seymour NE, Gallagher AG, Roman SA, et al. Virtual real-ity training improves operating room performance: results of a randomized, double-blinded study. Ann Surg. 2002;236(4): 458-463; discussion 463. 103. Anvari M. Telesurgery: remote knowledge translation in clinical surgery. World J Surg. 2007;31(8):1545-1550.Brunicardi_Ch14_p0453-p0478.indd 47801/03/19 4:59 PM
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Surgery_Schwartz. and Laparoscopic Surgery. Philadelphia: Lippincott, Williams & Wilkins; 2000:57. 101. Gallagher AG, Smith CD, Bowers SP, et al. Psychomotor skills assessment in practicing surgeons experienced in per-forming advanced laparoscopic procedures. J Am Coll Surg. 2003;197(3):479-488. 102. Seymour NE, Gallagher AG, Roman SA, et al. Virtual real-ity training improves operating room performance: results of a randomized, double-blinded study. Ann Surg. 2002;236(4): 458-463; discussion 463. 103. Anvari M. Telesurgery: remote knowledge translation in clinical surgery. World J Surg. 2007;31(8):1545-1550.Brunicardi_Ch14_p0453-p0478.indd 47801/03/19 4:59 PM
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Molecular Biology, The Atomic Theory of Disease, and Precision SurgeryXin-Hua Feng, Xia Lin, Xinran Li, Juehua Yu, John Nemunaitis, and F. Charles Brunicardi 15chapterOVERVIEW OF MOLECULAR CELL BIOLOGYThe beginning of modern medicine can be traced back to centu-ries ago when physicians and scientists began studying human anatomy from cadavers in morgues and animal physiology fol-lowing hunting expeditions. Gradually, from the study of ani-mals and plants in greater detail and the discovery of microbes, scientific principles governing life led to the emergence of the biologic sciences. As biologic science developed and expanded, scientists and physicians began to utilize its principles to solve challenges of human diseases while continuing to explore the fundamentals of life in greater detail. With ever-evolving state-of-the-art scientific tools, our understanding of how cells, tis-sues, organs, and entire organisms function, down to the level of molecular and subatomic structure,
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Surgery_Schwartz. Molecular Biology, The Atomic Theory of Disease, and Precision SurgeryXin-Hua Feng, Xia Lin, Xinran Li, Juehua Yu, John Nemunaitis, and F. Charles Brunicardi 15chapterOVERVIEW OF MOLECULAR CELL BIOLOGYThe beginning of modern medicine can be traced back to centu-ries ago when physicians and scientists began studying human anatomy from cadavers in morgues and animal physiology fol-lowing hunting expeditions. Gradually, from the study of ani-mals and plants in greater detail and the discovery of microbes, scientific principles governing life led to the emergence of the biologic sciences. As biologic science developed and expanded, scientists and physicians began to utilize its principles to solve challenges of human diseases while continuing to explore the fundamentals of life in greater detail. With ever-evolving state-of-the-art scientific tools, our understanding of how cells, tis-sues, organs, and entire organisms function, down to the level of molecular and subatomic structure,
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detail. With ever-evolving state-of-the-art scientific tools, our understanding of how cells, tis-sues, organs, and entire organisms function, down to the level of molecular and subatomic structure, has resulted in modern biology with an enormous impact on modern healthcare and the discovery of amazing treatments for disease at an exponential pace. Significant progress has been made in molecular studies of organ development, cell signaling, and gene regulation. The advent of recombinant DNA technology, polymerase chain reac-tion (PCR) techniques, and next-generation genomic sequenc-ing, which resulted in the sequencing of the human genome, holds the potential to have a transformational influence on healthcare and society this century by not only broadening our understanding of the pathophysiology of disease, but also by bringing about necessary changes in personalized medicine.Today’s practicing surgeons are becoming increasingly aware that many modern surgical procedures rely on the
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Surgery_Schwartz. detail. With ever-evolving state-of-the-art scientific tools, our understanding of how cells, tis-sues, organs, and entire organisms function, down to the level of molecular and subatomic structure, has resulted in modern biology with an enormous impact on modern healthcare and the discovery of amazing treatments for disease at an exponential pace. Significant progress has been made in molecular studies of organ development, cell signaling, and gene regulation. The advent of recombinant DNA technology, polymerase chain reac-tion (PCR) techniques, and next-generation genomic sequenc-ing, which resulted in the sequencing of the human genome, holds the potential to have a transformational influence on healthcare and society this century by not only broadening our understanding of the pathophysiology of disease, but also by bringing about necessary changes in personalized medicine.Today’s practicing surgeons are becoming increasingly aware that many modern surgical procedures rely on the
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of disease, but also by bringing about necessary changes in personalized medicine.Today’s practicing surgeons are becoming increasingly aware that many modern surgical procedures rely on the infor-mation gained through molecular research (i.e., precision surgery). Genomic information, such as deleterious BRCA and RET proto-oncogene mutations, is being used to help direct prophylactic procedures to remove potentially harmful tissues before they do damage to patients. Molecular engineering has led to cancer-specific gene therapy that could serve in the near future as a more effective adjunct to surgical debulking of tumors than radiation or chemotherapy, so surgeons will benefit from a clear introduction to how basic biochemical and biologic principles relate to the developing area of molecular biology. This chapter reviews the current information on modern molecular biology for the surgical community.Basic Concepts of Molecular ResearchThe modern era of molecular biology, which has
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Surgery_Schwartz. of disease, but also by bringing about necessary changes in personalized medicine.Today’s practicing surgeons are becoming increasingly aware that many modern surgical procedures rely on the infor-mation gained through molecular research (i.e., precision surgery). Genomic information, such as deleterious BRCA and RET proto-oncogene mutations, is being used to help direct prophylactic procedures to remove potentially harmful tissues before they do damage to patients. Molecular engineering has led to cancer-specific gene therapy that could serve in the near future as a more effective adjunct to surgical debulking of tumors than radiation or chemotherapy, so surgeons will benefit from a clear introduction to how basic biochemical and biologic principles relate to the developing area of molecular biology. This chapter reviews the current information on modern molecular biology for the surgical community.Basic Concepts of Molecular ResearchThe modern era of molecular biology, which has
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biology. This chapter reviews the current information on modern molecular biology for the surgical community.Basic Concepts of Molecular ResearchThe modern era of molecular biology, which has been mainly concerned with how genes govern cell activity, began in 1953 when James D. Watson and Francis H. C. Crick made one of the greatest scientific discoveries by deducing the double-helical structure of deoxyribonucleic acid (DNA).1,2 The year 2003 marked the 50th anniversary of this great discovery. In the same year, the Human Genome Project completed with sequencing approximately 20,000 to 25,000 genes and 3 billion base pairs in human DNA.3 Before 1953, one of the most mysterious aspects of biology was how genetic material was precisely duplicated from one generation to the next. Although DNA had been implicated as genetic material, it was the base-paired structure of DNA that provided a logical inter-pretation of how a double helix could “unzip” to make copies of itself. This DNA
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Surgery_Schwartz. biology. This chapter reviews the current information on modern molecular biology for the surgical community.Basic Concepts of Molecular ResearchThe modern era of molecular biology, which has been mainly concerned with how genes govern cell activity, began in 1953 when James D. Watson and Francis H. C. Crick made one of the greatest scientific discoveries by deducing the double-helical structure of deoxyribonucleic acid (DNA).1,2 The year 2003 marked the 50th anniversary of this great discovery. In the same year, the Human Genome Project completed with sequencing approximately 20,000 to 25,000 genes and 3 billion base pairs in human DNA.3 Before 1953, one of the most mysterious aspects of biology was how genetic material was precisely duplicated from one generation to the next. Although DNA had been implicated as genetic material, it was the base-paired structure of DNA that provided a logical inter-pretation of how a double helix could “unzip” to make copies of itself. This DNA
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DNA had been implicated as genetic material, it was the base-paired structure of DNA that provided a logical inter-pretation of how a double helix could “unzip” to make copies of itself. This DNA synthesis, termed replication, immediately gave rise to the notion that a template was involved in the trans-fer of information between generations, and thus confirmed the suspicion that DNA carried an organism’s hereditary information.Within cells, DNA is packed tightly into chromosomes. One important feature of DNA as genetic material is its abil-ity to encode important information for all of a cell’s functions (Fig. 15-1). Based on the principles of base complementarity, scientists also discovered how information in DNA is accurately transferred into the protein structure. DNA serves as a template for RNA synthesis, termed transcription, including messenger RNA (mRNA, or the protein-encoding RNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). mRNA carries the informa-tion from DNA to make
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Surgery_Schwartz. DNA had been implicated as genetic material, it was the base-paired structure of DNA that provided a logical inter-pretation of how a double helix could “unzip” to make copies of itself. This DNA synthesis, termed replication, immediately gave rise to the notion that a template was involved in the trans-fer of information between generations, and thus confirmed the suspicion that DNA carried an organism’s hereditary information.Within cells, DNA is packed tightly into chromosomes. One important feature of DNA as genetic material is its abil-ity to encode important information for all of a cell’s functions (Fig. 15-1). Based on the principles of base complementarity, scientists also discovered how information in DNA is accurately transferred into the protein structure. DNA serves as a template for RNA synthesis, termed transcription, including messenger RNA (mRNA, or the protein-encoding RNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). mRNA carries the informa-tion from DNA to make
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for RNA synthesis, termed transcription, including messenger RNA (mRNA, or the protein-encoding RNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). mRNA carries the informa-tion from DNA to make proteins, termed translation, with the assistance of rRNA and tRNA. Each of these steps is precisely 12Overview of Molecular Cell Biology 479Basic Concepts of Molecular Research /479Molecular Approaches to Surgical Research /480Fundamentals of Molecular and Cell Biology 480DNA and Heredity /480Gene Regulation /481Human Genome /485Cell Cycle and Apoptosis /486Signal Transduction Pathways /487Gene Therapy and Molecular Drugs in Cancer /490Stem Cell Research /492The Atomic Theory of Disease /493Technologies of Molecular and Cell Biology 493DNA Cloning /493Detection of Nucleic Acids and Proteins /494Cell Manipulations /499Genetic Manipulations /500Precision Medicine and Surgery /505Targeted Genome Editing Using the CRISPR-Cas9 System /506Brunicardi_Ch15_p0479-p0510.indd 47918/02/19
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Surgery_Schwartz. for RNA synthesis, termed transcription, including messenger RNA (mRNA, or the protein-encoding RNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). mRNA carries the informa-tion from DNA to make proteins, termed translation, with the assistance of rRNA and tRNA. Each of these steps is precisely 12Overview of Molecular Cell Biology 479Basic Concepts of Molecular Research /479Molecular Approaches to Surgical Research /480Fundamentals of Molecular and Cell Biology 480DNA and Heredity /480Gene Regulation /481Human Genome /485Cell Cycle and Apoptosis /486Signal Transduction Pathways /487Gene Therapy and Molecular Drugs in Cancer /490Stem Cell Research /492The Atomic Theory of Disease /493Technologies of Molecular and Cell Biology 493DNA Cloning /493Detection of Nucleic Acids and Proteins /494Cell Manipulations /499Genetic Manipulations /500Precision Medicine and Surgery /505Targeted Genome Editing Using the CRISPR-Cas9 System /506Brunicardi_Ch15_p0479-p0510.indd 47918/02/19
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/494Cell Manipulations /499Genetic Manipulations /500Precision Medicine and Surgery /505Targeted Genome Editing Using the CRISPR-Cas9 System /506Brunicardi_Ch15_p0479-p0510.indd 47918/02/19 11:12 AM 480Figure 15-1. The flow of genetic information from DNA to pro-tein to cell functions. The process of transmission of genetic infor-mation from DNA to RNA is called transcription, and the process of transmission from RNA to protein is called translation. Proteins are the essential controlling components for cell structure, cell sig-naling, and metabolism. Genomics and proteomics are the study of the genetic composition of a living organism at the DNA and pro-tein level, respectively. The study of the relationship between genes and their cellular functions is called functional genomics.Key Points1 The biologic sciences have developed drastically in the last 66 years after the uncovering of DNA structure by Watson and Crick.2 The completion of the human genome sequence in 2003
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Surgery_Schwartz. /494Cell Manipulations /499Genetic Manipulations /500Precision Medicine and Surgery /505Targeted Genome Editing Using the CRISPR-Cas9 System /506Brunicardi_Ch15_p0479-p0510.indd 47918/02/19 11:12 AM 480Figure 15-1. The flow of genetic information from DNA to pro-tein to cell functions. The process of transmission of genetic infor-mation from DNA to RNA is called transcription, and the process of transmission from RNA to protein is called translation. Proteins are the essential controlling components for cell structure, cell sig-naling, and metabolism. Genomics and proteomics are the study of the genetic composition of a living organism at the DNA and pro-tein level, respectively. The study of the relationship between genes and their cellular functions is called functional genomics.Key Points1 The biologic sciences have developed drastically in the last 66 years after the uncovering of DNA structure by Watson and Crick.2 The completion of the human genome sequence in 2003
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Points1 The biologic sciences have developed drastically in the last 66 years after the uncovering of DNA structure by Watson and Crick.2 The completion of the human genome sequence in 2003 rep-resents a great milestone in modern science.3 The technology emerging from molecular and cellular biol-ogy has revolutionized the understanding of disease and will radically transform the practice of surgery.4 The use of genetically modified mouse models and cell lines using gene therapy and RNA interference therapy has greatly contributed to the understanding of the molecular basis for human diseases and targeted therapies.5 The sequencing of each individual’s genome has the poten-tial to improve the predication, prevention, and targeted treatment of disease, resulting in precision medicine and surgery.6 Fast-developing targeted genome editing tools like the CRISPR-Cas9 system greatly facilitate biomedical research in native conditions and have shown their potential in the treatment of genetic
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Surgery_Schwartz. Points1 The biologic sciences have developed drastically in the last 66 years after the uncovering of DNA structure by Watson and Crick.2 The completion of the human genome sequence in 2003 rep-resents a great milestone in modern science.3 The technology emerging from molecular and cellular biol-ogy has revolutionized the understanding of disease and will radically transform the practice of surgery.4 The use of genetically modified mouse models and cell lines using gene therapy and RNA interference therapy has greatly contributed to the understanding of the molecular basis for human diseases and targeted therapies.5 The sequencing of each individual’s genome has the poten-tial to improve the predication, prevention, and targeted treatment of disease, resulting in precision medicine and surgery.6 Fast-developing targeted genome editing tools like the CRISPR-Cas9 system greatly facilitate biomedical research in native conditions and have shown their potential in the treatment of genetic
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targeted genome editing tools like the CRISPR-Cas9 system greatly facilitate biomedical research in native conditions and have shown their potential in the treatment of genetic diseases, including cancers, with a high degree of personalization and precision.7 The use of functional genomics and modern molecular anal-yses will facilitate the discovery of actionable genes to guide choice of care, including precision surgery.GenomicsProteomicsFunctionalgenomicsDNA RNAProteinsTranscriptionTranslationStructureMetabolismSignalingCell functionscontrolled in such a way that genes are properly expressed in each cell at a specific time and location. In recent years, new classes of noncoding RNAs (ncRNA), for example, microRNA (or miRNA), piwi-interacting RNA (or piRNA), and long inter-genic noncoding RNA (or lincRNA), have been identified. Although the number of ncRNAs encoded in the human genome is unknown and a lot of ncRNAs have not been validated for their functions, ncRNAs have been
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Surgery_Schwartz. targeted genome editing tools like the CRISPR-Cas9 system greatly facilitate biomedical research in native conditions and have shown their potential in the treatment of genetic diseases, including cancers, with a high degree of personalization and precision.7 The use of functional genomics and modern molecular anal-yses will facilitate the discovery of actionable genes to guide choice of care, including precision surgery.GenomicsProteomicsFunctionalgenomicsDNA RNAProteinsTranscriptionTranslationStructureMetabolismSignalingCell functionscontrolled in such a way that genes are properly expressed in each cell at a specific time and location. In recent years, new classes of noncoding RNAs (ncRNA), for example, microRNA (or miRNA), piwi-interacting RNA (or piRNA), and long inter-genic noncoding RNA (or lincRNA), have been identified. Although the number of ncRNAs encoded in the human genome is unknown and a lot of ncRNAs have not been validated for their functions, ncRNAs have been
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RNA (or lincRNA), have been identified. Although the number of ncRNAs encoded in the human genome is unknown and a lot of ncRNAs have not been validated for their functions, ncRNAs have been associated to regulate gene expression through posttranscriptional gene regulation such as mRNA degradation or epigenetic regulation such as chromatin structure modification and DNA methylation induction.4 Con-sequently, the differential gene activity in a cell determines its actions, properties, and functions.Molecular Approaches to Surgical ResearchRapid advances in molecular and cellular biology over the past half century have revolutionized the understanding of disease and will radically transform the practice of surgery. In the future, molecular techniques will be increasingly applied to surgical disease and will lead to new strategies for the selection and implementation of operative therapy. Surgeons should be familiar with the fundamental principles of molecular and cel-lular biology so
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Surgery_Schwartz. RNA (or lincRNA), have been identified. Although the number of ncRNAs encoded in the human genome is unknown and a lot of ncRNAs have not been validated for their functions, ncRNAs have been associated to regulate gene expression through posttranscriptional gene regulation such as mRNA degradation or epigenetic regulation such as chromatin structure modification and DNA methylation induction.4 Con-sequently, the differential gene activity in a cell determines its actions, properties, and functions.Molecular Approaches to Surgical ResearchRapid advances in molecular and cellular biology over the past half century have revolutionized the understanding of disease and will radically transform the practice of surgery. In the future, molecular techniques will be increasingly applied to surgical disease and will lead to new strategies for the selection and implementation of operative therapy. Surgeons should be familiar with the fundamental principles of molecular and cel-lular biology so
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disease and will lead to new strategies for the selection and implementation of operative therapy. Surgeons should be familiar with the fundamental principles of molecular and cel-lular biology so that emerging scientific breakthroughs can be translated into improved care of the surgical patient.The greatest advances in the field of molecular biology have been in the areas of analysis and manipulation of DNA.1 Since Watson and Crick’s discovery of DNA structure, an inten-sive effort has been made to unlock the deepest biologic secrets of DNA. Among the avalanche of technical advances, one dis-covery in particular has drastically changed the world of molec-ular biology: the uncovering of the enzymatic and microbiologic techniques that produce recombinant DNA. Recombinant DNA technology involves the enzymatic manipulation of DNA and, subsequently, the cloning of DNA. DNA molecules are cloned for a variety of purposes including safeguarding DNA samples, facilitating sequencing,
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Surgery_Schwartz. disease and will lead to new strategies for the selection and implementation of operative therapy. Surgeons should be familiar with the fundamental principles of molecular and cel-lular biology so that emerging scientific breakthroughs can be translated into improved care of the surgical patient.The greatest advances in the field of molecular biology have been in the areas of analysis and manipulation of DNA.1 Since Watson and Crick’s discovery of DNA structure, an inten-sive effort has been made to unlock the deepest biologic secrets of DNA. Among the avalanche of technical advances, one dis-covery in particular has drastically changed the world of molec-ular biology: the uncovering of the enzymatic and microbiologic techniques that produce recombinant DNA. Recombinant DNA technology involves the enzymatic manipulation of DNA and, subsequently, the cloning of DNA. DNA molecules are cloned for a variety of purposes including safeguarding DNA samples, facilitating sequencing,
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involves the enzymatic manipulation of DNA and, subsequently, the cloning of DNA. DNA molecules are cloned for a variety of purposes including safeguarding DNA samples, facilitating sequencing, generating probes, and expressing recombinant proteins in one or more host organisms. DNA can be produced by a number of means, including restricted diges-tion of an existing vector, PCR, and cDNA synthesis. As DNA cloning techniques have developed over the last quarter cen-tury, researchers have moved from studying DNA to studying the functions of proteins, and from cell and animal models to molecular therapies in humans. Expression of recombinant pro-teins provides a method for analyzing gene regulation, structure, and function. In recent years, the uses for recombinant proteins have expanded to include a variety of new applications, includ-ing gene therapy and biopharmaceuticals. The basic molecular approaches for modern surgical research include DNA cloning, cell manipulation, disease
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Surgery_Schwartz. involves the enzymatic manipulation of DNA and, subsequently, the cloning of DNA. DNA molecules are cloned for a variety of purposes including safeguarding DNA samples, facilitating sequencing, generating probes, and expressing recombinant proteins in one or more host organisms. DNA can be produced by a number of means, including restricted diges-tion of an existing vector, PCR, and cDNA synthesis. As DNA cloning techniques have developed over the last quarter cen-tury, researchers have moved from studying DNA to studying the functions of proteins, and from cell and animal models to molecular therapies in humans. Expression of recombinant pro-teins provides a method for analyzing gene regulation, structure, and function. In recent years, the uses for recombinant proteins have expanded to include a variety of new applications, includ-ing gene therapy and biopharmaceuticals. The basic molecular approaches for modern surgical research include DNA cloning, cell manipulation, disease
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to include a variety of new applications, includ-ing gene therapy and biopharmaceuticals. The basic molecular approaches for modern surgical research include DNA cloning, cell manipulation, disease modeling in animals, and clinical tri-als in human patients.FUNDAMENTALS OF MOLECULAR AND CELL BIOLOGYDNA and HeredityDNA forms a right-handed, double-helical structure that is composed of two antiparallel strands of unbranched polymeric deoxyribonucleotides linked by phosphodiester bonds between the 5′ carbon of one deoxyribose moiety to the 3′ carbon of the next (Fig. 15-2). DNA is composed of four types of deoxyribo-nucleotides: adenine (A), cytosine (C), guanine (G), and thy-mine (T). The nucleotides are joined together by phosphodiester bonds. In the double-helical structure deduced by Watson and Crick, the two strands of DNA are complementary to each other. Brunicardi_Ch15_p0479-p0510.indd 48018/02/19 11:12 AM 481MOLECULAR BIOLOGY, THE ATOMIC THEORY OF DISEASE, AND PRECISION
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Surgery_Schwartz. to include a variety of new applications, includ-ing gene therapy and biopharmaceuticals. The basic molecular approaches for modern surgical research include DNA cloning, cell manipulation, disease modeling in animals, and clinical tri-als in human patients.FUNDAMENTALS OF MOLECULAR AND CELL BIOLOGYDNA and HeredityDNA forms a right-handed, double-helical structure that is composed of two antiparallel strands of unbranched polymeric deoxyribonucleotides linked by phosphodiester bonds between the 5′ carbon of one deoxyribose moiety to the 3′ carbon of the next (Fig. 15-2). DNA is composed of four types of deoxyribo-nucleotides: adenine (A), cytosine (C), guanine (G), and thy-mine (T). The nucleotides are joined together by phosphodiester bonds. In the double-helical structure deduced by Watson and Crick, the two strands of DNA are complementary to each other. Brunicardi_Ch15_p0479-p0510.indd 48018/02/19 11:12 AM 481MOLECULAR BIOLOGY, THE ATOMIC THEORY OF DISEASE, AND PRECISION
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Watson and Crick, the two strands of DNA are complementary to each other. Brunicardi_Ch15_p0479-p0510.indd 48018/02/19 11:12 AM 481MOLECULAR BIOLOGY, THE ATOMIC THEORY OF DISEASE, AND PRECISION SURGERYCHAPTER 15Building blocks of DNAGTGGCCTAAA5'3'3'5'ATCGATGGCCTAGGCTTA3'5'5'3'5'3'GGGCTADNA strandCAGGCCTTTASugarphosphatePhosphateSugarBaseDouble-stranded DNADNA double helixSugar-phosphatebackboneHydrogen-bondedpairs+NucleotideFigure 15-2. Schematic representation of a DNA molecule form-ing a double helix. DNA is made of four types of nucleotides, which are linked covalently into a DNA strand. A DNA molecule is composed of two DNA strands held together by hydrogen bonds between the pair bases. The arrowheads at the ends of the DNA strands indicate the polarities of the two strands, which run anti-parallel to each other in the DNA molecule. The diagram at the bottom left of the figure shows the DNA molecule straightened out. In reality, the DNA molecule is twisted into a double helix,
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Surgery_Schwartz. Watson and Crick, the two strands of DNA are complementary to each other. Brunicardi_Ch15_p0479-p0510.indd 48018/02/19 11:12 AM 481MOLECULAR BIOLOGY, THE ATOMIC THEORY OF DISEASE, AND PRECISION SURGERYCHAPTER 15Building blocks of DNAGTGGCCTAAA5'3'3'5'ATCGATGGCCTAGGCTTA3'5'5'3'5'3'GGGCTADNA strandCAGGCCTTTASugarphosphatePhosphateSugarBaseDouble-stranded DNADNA double helixSugar-phosphatebackboneHydrogen-bondedpairs+NucleotideFigure 15-2. Schematic representation of a DNA molecule form-ing a double helix. DNA is made of four types of nucleotides, which are linked covalently into a DNA strand. A DNA molecule is composed of two DNA strands held together by hydrogen bonds between the pair bases. The arrowheads at the ends of the DNA strands indicate the polarities of the two strands, which run anti-parallel to each other in the DNA molecule. The diagram at the bottom left of the figure shows the DNA molecule straightened out. In reality, the DNA molecule is twisted into a double helix,
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run anti-parallel to each other in the DNA molecule. The diagram at the bottom left of the figure shows the DNA molecule straightened out. In reality, the DNA molecule is twisted into a double helix, of which each turn of DNA is made up of 10.4 nucleotide pairs, as shown on the right.Because of size, shape, and chemical composition, A always pairs with T, and C with G, through the formation of hydrogen bonds between complementary bases that stabilize the double helix.Recognition of the hereditary transmission of genetic information is attributed to the Austrian monk, Gregor Mendel. His seminal work, ignored upon publication until its rediscovery in 1900, established the laws of segregation and of independent assortment. These two principles established the existence of paired elementary units of heredity and defined the statistical laws that govern them.5 DNA was isolated in 1869, and a number of important observations of the inherited basis of certain dis-eases were made in the early
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Surgery_Schwartz. run anti-parallel to each other in the DNA molecule. The diagram at the bottom left of the figure shows the DNA molecule straightened out. In reality, the DNA molecule is twisted into a double helix, of which each turn of DNA is made up of 10.4 nucleotide pairs, as shown on the right.Because of size, shape, and chemical composition, A always pairs with T, and C with G, through the formation of hydrogen bonds between complementary bases that stabilize the double helix.Recognition of the hereditary transmission of genetic information is attributed to the Austrian monk, Gregor Mendel. His seminal work, ignored upon publication until its rediscovery in 1900, established the laws of segregation and of independent assortment. These two principles established the existence of paired elementary units of heredity and defined the statistical laws that govern them.5 DNA was isolated in 1869, and a number of important observations of the inherited basis of certain dis-eases were made in the early
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of heredity and defined the statistical laws that govern them.5 DNA was isolated in 1869, and a number of important observations of the inherited basis of certain dis-eases were made in the early part of the 20th century. Although today it appears easy to understand how DNA replicates, before the 1950s the idea of DNA as the primary genetic material was not appreciated. The modern era of molecular biology began in 1944 with the demonstration that DNA was the substance that carried genetic information. The first experimental evidence that DNA was genetic material came from simple transforma-tion experiments conducted in the 1940s using Streptococcus pneumoniae. One strain of the bacteria could be converted into another by incubating it with DNA from the other, just as the treatment of the DNA with deoxyribonuclease would inactivate the transforming activity of the DNA. Similarly, in the early 1950s, before the discovery of the double-helical structure of DNA, the entry of viral DNA and
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Surgery_Schwartz. of heredity and defined the statistical laws that govern them.5 DNA was isolated in 1869, and a number of important observations of the inherited basis of certain dis-eases were made in the early part of the 20th century. Although today it appears easy to understand how DNA replicates, before the 1950s the idea of DNA as the primary genetic material was not appreciated. The modern era of molecular biology began in 1944 with the demonstration that DNA was the substance that carried genetic information. The first experimental evidence that DNA was genetic material came from simple transforma-tion experiments conducted in the 1940s using Streptococcus pneumoniae. One strain of the bacteria could be converted into another by incubating it with DNA from the other, just as the treatment of the DNA with deoxyribonuclease would inactivate the transforming activity of the DNA. Similarly, in the early 1950s, before the discovery of the double-helical structure of DNA, the entry of viral DNA and
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with deoxyribonuclease would inactivate the transforming activity of the DNA. Similarly, in the early 1950s, before the discovery of the double-helical structure of DNA, the entry of viral DNA and not the protein into the host bacterium was believed to be necessary to initiate infection by the bacterial virus or bacteriophage. Key historical events con-cerning genetics are outlined in Table 15-1.For cells to pass on the genetic material (DNA) to each progeny, the amount of DNA must be doubled. Watson and Crick recognized that the complementary base-pair structure of DNA implied the existence of a template-like mechanism for the copying of genetic material.1 The transfer of DNA material from the mother cell to daughter cells takes place during somatic cell division (also called mitosis). Before a cell divides, DNA must be precisely duplicated. During replication, the two strands of DNA separate, and each strand creates a new complementary strand by precise base-pair matching (Fig.
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Surgery_Schwartz. with deoxyribonuclease would inactivate the transforming activity of the DNA. Similarly, in the early 1950s, before the discovery of the double-helical structure of DNA, the entry of viral DNA and not the protein into the host bacterium was believed to be necessary to initiate infection by the bacterial virus or bacteriophage. Key historical events con-cerning genetics are outlined in Table 15-1.For cells to pass on the genetic material (DNA) to each progeny, the amount of DNA must be doubled. Watson and Crick recognized that the complementary base-pair structure of DNA implied the existence of a template-like mechanism for the copying of genetic material.1 The transfer of DNA material from the mother cell to daughter cells takes place during somatic cell division (also called mitosis). Before a cell divides, DNA must be precisely duplicated. During replication, the two strands of DNA separate, and each strand creates a new complementary strand by precise base-pair matching (Fig.
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Before a cell divides, DNA must be precisely duplicated. During replication, the two strands of DNA separate, and each strand creates a new complementary strand by precise base-pair matching (Fig. 15-3). The two, new, double-stranded DNAs carry the same genetic information, which can then be passed on to two daughter cells. Proofread-ing mechanisms ensure that the replication process occurs in a highly accurate manner. The fidelity of DNA replication is absolutely crucial to maintaining the integrity of the genome from generation to generation. However, mistakes can still occur during this process, resulting in mutations, which may lead to a change of the DNA’s encoded protein and, consequently, a change of the cell’s behavior. The reliable dependence of many features of modern organisms on subtle changes in genome is linked to Mendelian inheritance and also contributes to the pro-cesses of Darwinian evolution. In addition, massive changes, so-called genetic instability, can occur in
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Surgery_Schwartz. Before a cell divides, DNA must be precisely duplicated. During replication, the two strands of DNA separate, and each strand creates a new complementary strand by precise base-pair matching (Fig. 15-3). The two, new, double-stranded DNAs carry the same genetic information, which can then be passed on to two daughter cells. Proofread-ing mechanisms ensure that the replication process occurs in a highly accurate manner. The fidelity of DNA replication is absolutely crucial to maintaining the integrity of the genome from generation to generation. However, mistakes can still occur during this process, resulting in mutations, which may lead to a change of the DNA’s encoded protein and, consequently, a change of the cell’s behavior. The reliable dependence of many features of modern organisms on subtle changes in genome is linked to Mendelian inheritance and also contributes to the pro-cesses of Darwinian evolution. In addition, massive changes, so-called genetic instability, can occur in
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on subtle changes in genome is linked to Mendelian inheritance and also contributes to the pro-cesses of Darwinian evolution. In addition, massive changes, so-called genetic instability, can occur in the genome of somatic cells such as cancer cells.Gene RegulationLiving cells have the necessary machinery to enzymatically transcribe DNA into RNA and translate the mRNA into pro-tein. This machinery accomplishes the two major steps required for gene expression in all organisms: transcription and trans-lation (Fig. 15-4). However, gene regulation is far more com-plex, particularly in eukaryotic organisms. For example, many gene transcripts must be spliced to remove the intervening sequences. The sequences that are spliced off are called introns, which appear to be useless, but in fact may carry some regula-tory information. The sequences that are joined together, and are eventually translated into protein, are called exons. Additional regulation of gene expression includes modification of
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Surgery_Schwartz. on subtle changes in genome is linked to Mendelian inheritance and also contributes to the pro-cesses of Darwinian evolution. In addition, massive changes, so-called genetic instability, can occur in the genome of somatic cells such as cancer cells.Gene RegulationLiving cells have the necessary machinery to enzymatically transcribe DNA into RNA and translate the mRNA into pro-tein. This machinery accomplishes the two major steps required for gene expression in all organisms: transcription and trans-lation (Fig. 15-4). However, gene regulation is far more com-plex, particularly in eukaryotic organisms. For example, many gene transcripts must be spliced to remove the intervening sequences. The sequences that are spliced off are called introns, which appear to be useless, but in fact may carry some regula-tory information. The sequences that are joined together, and are eventually translated into protein, are called exons. Additional regulation of gene expression includes modification of
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some regula-tory information. The sequences that are joined together, and are eventually translated into protein, are called exons. Additional regulation of gene expression includes modification of mRNA, control of mRNA stability, and its nuclear export into cytoplasm (where it is assembled into ribosomes for translation). After mRNA is translated into protein, the levels and functions of the proteins can be further regulated posttranslationally. However, the following sections will mainly focus on gene regulation at transcriptional and translational levels.Transcription. Transcription is the enzymatic process of RNA synthesis from DNA.6 In bacteria, a single RNA polymerase carries out all RNA synthesis, including that of mRNA, rRNA, Brunicardi_Ch15_p0479-p0510.indd 48118/02/19 11:12 AM 482BASIC CONSIDERATIONSPART IFigure 15-3. DNA replication. As the nucleotide A only pairs with T, and G with C, each strand of DNA can determine the nucleotide sequence in its complementary strand.
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Surgery_Schwartz. some regula-tory information. The sequences that are joined together, and are eventually translated into protein, are called exons. Additional regulation of gene expression includes modification of mRNA, control of mRNA stability, and its nuclear export into cytoplasm (where it is assembled into ribosomes for translation). After mRNA is translated into protein, the levels and functions of the proteins can be further regulated posttranslationally. However, the following sections will mainly focus on gene regulation at transcriptional and translational levels.Transcription. Transcription is the enzymatic process of RNA synthesis from DNA.6 In bacteria, a single RNA polymerase carries out all RNA synthesis, including that of mRNA, rRNA, Brunicardi_Ch15_p0479-p0510.indd 48118/02/19 11:12 AM 482BASIC CONSIDERATIONSPART IFigure 15-3. DNA replication. As the nucleotide A only pairs with T, and G with C, each strand of DNA can determine the nucleotide sequence in its complementary strand.
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482BASIC CONSIDERATIONSPART IFigure 15-3. DNA replication. As the nucleotide A only pairs with T, and G with C, each strand of DNA can determine the nucleotide sequence in its complementary strand. In this way, double-helical DNA can be copied precisely.Table 15-1Historical events in genetics and molecular biologyYEARINVESTIGATOREVENT1865MendelLaws of genetics established1869MiescherDNA isolated1905GarrodHuman inborn errors of metabolism1913SturtevantLinear map of genes1927MullerX-rays cause inheritable genetic damage1928GriffithTransformation discovered1941Beadle and Tatum“One gene, one enzyme” concept1944Avery, MacLeod, McCartyDNA as material of heredity1950McKlintockExistence of transposons confirmed1953Watson and CrickDouble-helical structure of DNA1957Benzer and KornbergRecombination and DNA polymerase1966Nirenberg, Khorana, HolleyGenetic code determined1970Temin and BaltimoreReverse transcriptase1972Cohen, Boyer, BergRecombinant DNA technology1975SouthernTransfer of DNA
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Surgery_Schwartz. 482BASIC CONSIDERATIONSPART IFigure 15-3. DNA replication. As the nucleotide A only pairs with T, and G with C, each strand of DNA can determine the nucleotide sequence in its complementary strand. In this way, double-helical DNA can be copied precisely.Table 15-1Historical events in genetics and molecular biologyYEARINVESTIGATOREVENT1865MendelLaws of genetics established1869MiescherDNA isolated1905GarrodHuman inborn errors of metabolism1913SturtevantLinear map of genes1927MullerX-rays cause inheritable genetic damage1928GriffithTransformation discovered1941Beadle and Tatum“One gene, one enzyme” concept1944Avery, MacLeod, McCartyDNA as material of heredity1950McKlintockExistence of transposons confirmed1953Watson and CrickDouble-helical structure of DNA1957Benzer and KornbergRecombination and DNA polymerase1966Nirenberg, Khorana, HolleyGenetic code determined1970Temin and BaltimoreReverse transcriptase1972Cohen, Boyer, BergRecombinant DNA technology1975SouthernTransfer of DNA
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and DNA polymerase1966Nirenberg, Khorana, HolleyGenetic code determined1970Temin and BaltimoreReverse transcriptase1972Cohen, Boyer, BergRecombinant DNA technology1975SouthernTransfer of DNA fragments from sizing gel to nitrocellulose (Southern blot)1977Sanger, Maxim, GilbertDNA sequencing methods1982—GenBank database established1985MullisPolymerase chain reaction1986—Automated DNA sequencing1989CollinsCystic fibrosis gene identified by positional cloning and linkage analysis1990—Human Genome Project initiated1997Roslin InstituteMammalian cloning (Dolly)2001IHGSC and Celera GenomicsDraft versions of human genome sequence published2003—Human Genome Project completedIHGSC = International Human Genome Sequencing Consortium.GTGGCCTAAACAGGCCTTTACAGGCCTTTAGTGGCCTAAACAGGCCTTTAGTGGCCTAAAS strandS strandNew S strandNew S strandTemplate S strandTemplate S strand5'3'3'5'5'5'5'5'3'3'3'Parent DNA double helix (shown flat):3'DNA is a template for its own duplicationBrunicardi_Ch15_p0479-p0510.indd
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Surgery_Schwartz. and DNA polymerase1966Nirenberg, Khorana, HolleyGenetic code determined1970Temin and BaltimoreReverse transcriptase1972Cohen, Boyer, BergRecombinant DNA technology1975SouthernTransfer of DNA fragments from sizing gel to nitrocellulose (Southern blot)1977Sanger, Maxim, GilbertDNA sequencing methods1982—GenBank database established1985MullisPolymerase chain reaction1986—Automated DNA sequencing1989CollinsCystic fibrosis gene identified by positional cloning and linkage analysis1990—Human Genome Project initiated1997Roslin InstituteMammalian cloning (Dolly)2001IHGSC and Celera GenomicsDraft versions of human genome sequence published2003—Human Genome Project completedIHGSC = International Human Genome Sequencing Consortium.GTGGCCTAAACAGGCCTTTACAGGCCTTTAGTGGCCTAAACAGGCCTTTAGTGGCCTAAAS strandS strandNew S strandNew S strandTemplate S strandTemplate S strand5'3'3'5'5'5'5'5'3'3'3'Parent DNA double helix (shown flat):3'DNA is a template for its own duplicationBrunicardi_Ch15_p0479-p0510.indd
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strandNew S strandNew S strandTemplate S strandTemplate S strand5'3'3'5'5'5'5'5'3'3'3'Parent DNA double helix (shown flat):3'DNA is a template for its own duplicationBrunicardi_Ch15_p0479-p0510.indd 48218/02/19 11:12 AM 483MOLECULAR BIOLOGY, THE ATOMIC THEORY OF DISEASE, AND PRECISION SURGERYCHAPTER 15NucleusCytoplasmDNARNAtranscriptmRNAmRNAProteinActiveproteinmRNAturnoverProteinturnoverTranscriptionRNAtransportTranscriptionalcontrolPosttranscriptionalcontrolTranslationalcontrolPosttranslationalcontrolNuclear envelopeRNAdegradationProteindegradationPosttranslationalmodificationTranslationRNAprocessingFigure 15-4. Four major steps in the control of eukaryotic gene expression. Transcriptional and posttranscriptional control determine the level of messenger RNA (mRNA) that is available to make a protein, while translational and posttranslational control determine the final outcome of functional proteins. Note that posttranscriptional and posttranslational controls consist of several
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Surgery_Schwartz. strandNew S strandNew S strandTemplate S strandTemplate S strand5'3'3'5'5'5'5'5'3'3'3'Parent DNA double helix (shown flat):3'DNA is a template for its own duplicationBrunicardi_Ch15_p0479-p0510.indd 48218/02/19 11:12 AM 483MOLECULAR BIOLOGY, THE ATOMIC THEORY OF DISEASE, AND PRECISION SURGERYCHAPTER 15NucleusCytoplasmDNARNAtranscriptmRNAmRNAProteinActiveproteinmRNAturnoverProteinturnoverTranscriptionRNAtransportTranscriptionalcontrolPosttranscriptionalcontrolTranslationalcontrolPosttranslationalcontrolNuclear envelopeRNAdegradationProteindegradationPosttranslationalmodificationTranslationRNAprocessingFigure 15-4. Four major steps in the control of eukaryotic gene expression. Transcriptional and posttranscriptional control determine the level of messenger RNA (mRNA) that is available to make a protein, while translational and posttranslational control determine the final outcome of functional proteins. Note that posttranscriptional and posttranslational controls consist of several
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make a protein, while translational and posttranslational control determine the final outcome of functional proteins. Note that posttranscriptional and posttranslational controls consist of several steps.and tRNA. Transcription often is coupled with translation in such a way that an mRNA molecule is completely accessible to ribosomes, and bacterial protein synthesis begins on an mRNA molecule even while it is still being synthesized. Therefore, a discussion of gene regulation with a look at the simpler prokary-otic system precedes that of the more complex transcription and posttranscriptional regulation of eukaryotic genes.Transcription in Bacteria Initiation of transcription in pro-karyotes begins with the recognition of DNA sequences by RNA polymerase. First, the bacterial RNA polymerase cata-lyzes RNA synthesis through loose binding to any region in the double-stranded DNA and then through specific binding to the promoter region with the assistance of accessory pro-teins called σ
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Surgery_Schwartz. make a protein, while translational and posttranslational control determine the final outcome of functional proteins. Note that posttranscriptional and posttranslational controls consist of several steps.and tRNA. Transcription often is coupled with translation in such a way that an mRNA molecule is completely accessible to ribosomes, and bacterial protein synthesis begins on an mRNA molecule even while it is still being synthesized. Therefore, a discussion of gene regulation with a look at the simpler prokary-otic system precedes that of the more complex transcription and posttranscriptional regulation of eukaryotic genes.Transcription in Bacteria Initiation of transcription in pro-karyotes begins with the recognition of DNA sequences by RNA polymerase. First, the bacterial RNA polymerase cata-lyzes RNA synthesis through loose binding to any region in the double-stranded DNA and then through specific binding to the promoter region with the assistance of accessory pro-teins called σ
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cata-lyzes RNA synthesis through loose binding to any region in the double-stranded DNA and then through specific binding to the promoter region with the assistance of accessory pro-teins called σ factors (sigma factors). A promoter region is the DNA region upstream of the transcription initiation site. RNA polymerase binds tightly at the promoter sites and causes the double-stranded DNA structure to unwind. Consequently, few nucleotides can be base-paired with the DNA template to begin transcription. Once transcription begins, the σ factor is released. The growing RNA chain may begin to peel off as the chain elongates. This occurs in such a way that there are always about 10 to 12 nucleotides of the growing RNA chains that are base-paired with the DNA template.The bacterial promoter contains a region of about 40 bases that include two conserved elements called –35 region and –10 region. The numbering system begins at the initiation site, which is designated +1 position, and counts
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Surgery_Schwartz. cata-lyzes RNA synthesis through loose binding to any region in the double-stranded DNA and then through specific binding to the promoter region with the assistance of accessory pro-teins called σ factors (sigma factors). A promoter region is the DNA region upstream of the transcription initiation site. RNA polymerase binds tightly at the promoter sites and causes the double-stranded DNA structure to unwind. Consequently, few nucleotides can be base-paired with the DNA template to begin transcription. Once transcription begins, the σ factor is released. The growing RNA chain may begin to peel off as the chain elongates. This occurs in such a way that there are always about 10 to 12 nucleotides of the growing RNA chains that are base-paired with the DNA template.The bacterial promoter contains a region of about 40 bases that include two conserved elements called –35 region and –10 region. The numbering system begins at the initiation site, which is designated +1 position, and counts
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a region of about 40 bases that include two conserved elements called –35 region and –10 region. The numbering system begins at the initiation site, which is designated +1 position, and counts backward (in nega-tive numbers) on the promoter and forward on the transcribed region. Although both regions on different promoters are not the same sequences, they are fairly conserved and very similar. This conservation provides the accurate and rapid initiation of transcription for most bacterial genes. It is also common in bac-teria that one promoter serves to transcribe a series of clustered genes, called an operon. A single transcribed mRNA contains a series of coding regions, each of which is later independently translated. In this way, the protein products are synthesized in a coordinated manner. Most of the time, these proteins are involved in the same metabolic pathway, thus demonstrating that the control by one operon is an efficient system. After ini-tiation of transcription, the
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Surgery_Schwartz. a region of about 40 bases that include two conserved elements called –35 region and –10 region. The numbering system begins at the initiation site, which is designated +1 position, and counts backward (in nega-tive numbers) on the promoter and forward on the transcribed region. Although both regions on different promoters are not the same sequences, they are fairly conserved and very similar. This conservation provides the accurate and rapid initiation of transcription for most bacterial genes. It is also common in bac-teria that one promoter serves to transcribe a series of clustered genes, called an operon. A single transcribed mRNA contains a series of coding regions, each of which is later independently translated. In this way, the protein products are synthesized in a coordinated manner. Most of the time, these proteins are involved in the same metabolic pathway, thus demonstrating that the control by one operon is an efficient system. After ini-tiation of transcription, the
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manner. Most of the time, these proteins are involved in the same metabolic pathway, thus demonstrating that the control by one operon is an efficient system. After ini-tiation of transcription, the polymerase moves along the DNA to elongate the chain of RNA, although at a certain point, it will stop. Each step of RNA synthesis, including initiation, elongation, and termination, will require the integral functions of RNA polymerase as well as the interactions of the poly-merase with regulatory proteins.Transcription in Eukaryotes Transcription mechanisms in eukaryotes differ from those in prokaryotes. The unique features of eukaryotic transcription are as follows: (a) Three separate RNA polymerases are involved in eukaryotes: RNA polymerase I transcribes the precursor of 5.8S, 18S, and 28S rRNAs; RNA polymerase II synthesizes the precursors of mRNA as well as microRNA; and RNA polymerase III makes tRNAs and 5S rRNAs. (b) In eukaryotes, the initial transcript is often the pre-cursor to
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Surgery_Schwartz. manner. Most of the time, these proteins are involved in the same metabolic pathway, thus demonstrating that the control by one operon is an efficient system. After ini-tiation of transcription, the polymerase moves along the DNA to elongate the chain of RNA, although at a certain point, it will stop. Each step of RNA synthesis, including initiation, elongation, and termination, will require the integral functions of RNA polymerase as well as the interactions of the poly-merase with regulatory proteins.Transcription in Eukaryotes Transcription mechanisms in eukaryotes differ from those in prokaryotes. The unique features of eukaryotic transcription are as follows: (a) Three separate RNA polymerases are involved in eukaryotes: RNA polymerase I transcribes the precursor of 5.8S, 18S, and 28S rRNAs; RNA polymerase II synthesizes the precursors of mRNA as well as microRNA; and RNA polymerase III makes tRNAs and 5S rRNAs. (b) In eukaryotes, the initial transcript is often the pre-cursor to
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rRNAs; RNA polymerase II synthesizes the precursors of mRNA as well as microRNA; and RNA polymerase III makes tRNAs and 5S rRNAs. (b) In eukaryotes, the initial transcript is often the pre-cursor to final mRNAs, tRNAs, and rRNAs. The precursor is then modified and/or processed into its final functional form. RNA splicing is one type of processing to remove the noncoding introns (the region between coding exons) on an mRNA. (c) In contrast to bacterial DNA, eukaryotic DNA often is packaged with histone and nonhistone proteins into chromatins. Transcrip-tion will only occur when the chromatin structure changes in such a way that DNA is accessible to the polymerase. (d) RNA is made in the nucleus and transported into cytoplasm, where translation occurs. Therefore, unlike bacteria, eukaryotes undergo uncoupled transcription and translation.Eukaryotic gene transcription also involves the recogni-tion and binding of RNA polymerase to the promoter DNA. However, the interaction between the
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Surgery_Schwartz. rRNAs; RNA polymerase II synthesizes the precursors of mRNA as well as microRNA; and RNA polymerase III makes tRNAs and 5S rRNAs. (b) In eukaryotes, the initial transcript is often the pre-cursor to final mRNAs, tRNAs, and rRNAs. The precursor is then modified and/or processed into its final functional form. RNA splicing is one type of processing to remove the noncoding introns (the region between coding exons) on an mRNA. (c) In contrast to bacterial DNA, eukaryotic DNA often is packaged with histone and nonhistone proteins into chromatins. Transcrip-tion will only occur when the chromatin structure changes in such a way that DNA is accessible to the polymerase. (d) RNA is made in the nucleus and transported into cytoplasm, where translation occurs. Therefore, unlike bacteria, eukaryotes undergo uncoupled transcription and translation.Eukaryotic gene transcription also involves the recogni-tion and binding of RNA polymerase to the promoter DNA. However, the interaction between the
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undergo uncoupled transcription and translation.Eukaryotic gene transcription also involves the recogni-tion and binding of RNA polymerase to the promoter DNA. However, the interaction between the polymerase and DNA is far more complex in eukaryotes than in prokaryotes. Because the majority of studies have been focused on the regulation and functions of proteins, this chapter primarily focuses on how protein-encoding mRNA is made by RNA polymerase II.Translation. DNA directs the synthesis of RNA; RNA in turn directs the synthesis of proteins. Proteins are variable-length polypeptide polymers composed of various combinations of 20 different amino acids and are the working molecules of the cell. The process of decoding information on mRNA to synthesize proteins is called translation (see Fig. 15-1). Translation takes place in ribosomes composed of rRNA and ribosomal proteins. The numerous discoveries made during the 1950s made it easy to understand how DNA replication and transcription
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Surgery_Schwartz. undergo uncoupled transcription and translation.Eukaryotic gene transcription also involves the recogni-tion and binding of RNA polymerase to the promoter DNA. However, the interaction between the polymerase and DNA is far more complex in eukaryotes than in prokaryotes. Because the majority of studies have been focused on the regulation and functions of proteins, this chapter primarily focuses on how protein-encoding mRNA is made by RNA polymerase II.Translation. DNA directs the synthesis of RNA; RNA in turn directs the synthesis of proteins. Proteins are variable-length polypeptide polymers composed of various combinations of 20 different amino acids and are the working molecules of the cell. The process of decoding information on mRNA to synthesize proteins is called translation (see Fig. 15-1). Translation takes place in ribosomes composed of rRNA and ribosomal proteins. The numerous discoveries made during the 1950s made it easy to understand how DNA replication and transcription
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15-1). Translation takes place in ribosomes composed of rRNA and ribosomal proteins. The numerous discoveries made during the 1950s made it easy to understand how DNA replication and transcription involve base-pairing between DNA and DNA or DNA and RNA. How-ever, at that time, it was still impossible to comprehend how mRNA transfers the information to the protein-synthesizing machinery. The genetic information on mRNA is composed of Brunicardi_Ch15_p0479-p0510.indd 48318/02/19 11:12 AM 484BASIC CONSIDERATIONSPART ITable 15-2The genetic codeSECOND BASE IN CODON U C A G First Base in CodonUUUUPhe[F]UCUSer[S]UAUTyr[Y]UGUCys[C]UThird Base in
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Surgery_Schwartz. 15-1). Translation takes place in ribosomes composed of rRNA and ribosomal proteins. The numerous discoveries made during the 1950s made it easy to understand how DNA replication and transcription involve base-pairing between DNA and DNA or DNA and RNA. How-ever, at that time, it was still impossible to comprehend how mRNA transfers the information to the protein-synthesizing machinery. The genetic information on mRNA is composed of Brunicardi_Ch15_p0479-p0510.indd 48318/02/19 11:12 AM 484BASIC CONSIDERATIONSPART ITable 15-2The genetic codeSECOND BASE IN CODON U C A G First Base in CodonUUUUPhe[F]UCUSer[S]UAUTyr[Y]UGUCys[C]UThird Base in
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48318/02/19 11:12 AM 484BASIC CONSIDERATIONSPART ITable 15-2The genetic codeSECOND BASE IN CODON U C A G First Base in CodonUUUUPhe[F]UCUSer[S]UAUTyr[Y]UGUCys[C]UThird Base in Codon UUCPhe[F]UCCSer[S]UACTyr[Y]UGCCys[C]C UUALeu[L]UCASer[S]UAASTOP—UGASTOP—A UUGLeu[L]UCGSer[S]UAGSTOP—UGGTrp[W]G CCUULeu[L]CCUPro[P]CAUHis[H]CGUArg[R]U CUCLeu[L]CCCPro[P]CACHis[H]CGCArg[R]C CUALeu[L]CCAPro[P]CAAGln[Q]CGAArg[R]A CUGLeu[L]CCGPro[P]CAGGln[Q]CGGArg[R]G AAUUIle[I]ACUThr[T]AAUAsn[N]AGUSer[S]U AUCIle[I]ACCThr[T]AACAsn[N]AGCSer[S]C AUAIle[I]ACAThr[T]AAALys[K]AGAArg[R]A AUGMet[M]ACGThr[T]AAGLys[K]AGGArg[R]G GGUUVal[V]GCUAla[A]GAUAsp[D]GGUGly[G]U GUCVal[V]GCCAla[A]GACAsp[D]GGCGly[G]C GUAVal[V]GCAAla[A]GAAGlu[E]GGAGly[G]A GUGVal[V]GCGAla[A]GAGGlu[E]GGGGly[G]G A = adenine; C = cytosine; G = guanine; U = uracil; Ala = alanine; Arg = arginine; Asn = asparagine; Asp = aspartic acid; Cys = cysteine; Glu = glutamic acid; Gln = glutamine; Gly = glycine; His = histidine;
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Surgery_Schwartz. 48318/02/19 11:12 AM 484BASIC CONSIDERATIONSPART ITable 15-2The genetic codeSECOND BASE IN CODON U C A G First Base in CodonUUUUPhe[F]UCUSer[S]UAUTyr[Y]UGUCys[C]UThird Base in Codon UUCPhe[F]UCCSer[S]UACTyr[Y]UGCCys[C]C UUALeu[L]UCASer[S]UAASTOP—UGASTOP—A UUGLeu[L]UCGSer[S]UAGSTOP—UGGTrp[W]G CCUULeu[L]CCUPro[P]CAUHis[H]CGUArg[R]U CUCLeu[L]CCCPro[P]CACHis[H]CGCArg[R]C CUALeu[L]CCAPro[P]CAAGln[Q]CGAArg[R]A CUGLeu[L]CCGPro[P]CAGGln[Q]CGGArg[R]G AAUUIle[I]ACUThr[T]AAUAsn[N]AGUSer[S]U AUCIle[I]ACCThr[T]AACAsn[N]AGCSer[S]C AUAIle[I]ACAThr[T]AAALys[K]AGAArg[R]A AUGMet[M]ACGThr[T]AAGLys[K]AGGArg[R]G GGUUVal[V]GCUAla[A]GAUAsp[D]GGUGly[G]U GUCVal[V]GCCAla[A]GACAsp[D]GGCGly[G]C GUAVal[V]GCAAla[A]GAAGlu[E]GGAGly[G]A GUGVal[V]GCGAla[A]GAGGlu[E]GGGGly[G]G A = adenine; C = cytosine; G = guanine; U = uracil; Ala = alanine; Arg = arginine; Asn = asparagine; Asp = aspartic acid; Cys = cysteine; Glu = glutamic acid; Gln = glutamine; Gly = glycine; His = histidine;
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C = cytosine; G = guanine; U = uracil; Ala = alanine; Arg = arginine; Asn = asparagine; Asp = aspartic acid; Cys = cysteine; Glu = glutamic acid; Gln = glutamine; Gly = glycine; His = histidine; Ile = isoleucine; Leu = leucine; Lys = lysine; Met = methionine; Phe = phenylalanine; Pro = proline; Ser = serine; Thr = threonine; Trp = tryptophan; Tyr = tyrosine; Val = valine. Letter in [ ] indicates single letter code for amino acid.arranged sequences of four bases that are transferred to the lin-ear arrangement of 20 amino acids on a protein. Amino acids are characterized by a central carbon unit linked to four side chains: an amino group (–NH2), a carboxy group (–COOH), a hydrogen, and a variable (–R) group. The amino acid chain is assembled via peptide bonds between the amino group of one amino acid and the carboxy group of the next. Because of this decoding, the information carried on mRNA relies on tRNA. Translation involves all three RNAs. The precise transfer of information from
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Surgery_Schwartz. C = cytosine; G = guanine; U = uracil; Ala = alanine; Arg = arginine; Asn = asparagine; Asp = aspartic acid; Cys = cysteine; Glu = glutamic acid; Gln = glutamine; Gly = glycine; His = histidine; Ile = isoleucine; Leu = leucine; Lys = lysine; Met = methionine; Phe = phenylalanine; Pro = proline; Ser = serine; Thr = threonine; Trp = tryptophan; Tyr = tyrosine; Val = valine. Letter in [ ] indicates single letter code for amino acid.arranged sequences of four bases that are transferred to the lin-ear arrangement of 20 amino acids on a protein. Amino acids are characterized by a central carbon unit linked to four side chains: an amino group (–NH2), a carboxy group (–COOH), a hydrogen, and a variable (–R) group. The amino acid chain is assembled via peptide bonds between the amino group of one amino acid and the carboxy group of the next. Because of this decoding, the information carried on mRNA relies on tRNA. Translation involves all three RNAs. The precise transfer of information from
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amino acid and the carboxy group of the next. Because of this decoding, the information carried on mRNA relies on tRNA. Translation involves all three RNAs. The precise transfer of information from mRNA to protein is governed by genetic code, the set of rules by which codons are translated into an amino acid (Table 15-2). A codon, a triplet of three bases, codes for one amino acid. In this case, random combinations of the four bases form 4 × 4 × 4, or 64 codes. Because 64 codes are more than enough for 20 amino acids, most amino acids are coded by more than one codon. The start codon is AUG, which also corresponds to methionine; therefore, almost all proteins begin with this amino acid. The sequence of nucleotide triplets that follows the start codon signal is termed the reading frame. The codons on mRNA are sequentially recognized by tRNA adaptor proteins. Specific enzymes termed aminoacyl-tRNA synthetases link a specific amino acid to a specific tRNA. The translation of mRNA to
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Surgery_Schwartz. amino acid and the carboxy group of the next. Because of this decoding, the information carried on mRNA relies on tRNA. Translation involves all three RNAs. The precise transfer of information from mRNA to protein is governed by genetic code, the set of rules by which codons are translated into an amino acid (Table 15-2). A codon, a triplet of three bases, codes for one amino acid. In this case, random combinations of the four bases form 4 × 4 × 4, or 64 codes. Because 64 codes are more than enough for 20 amino acids, most amino acids are coded by more than one codon. The start codon is AUG, which also corresponds to methionine; therefore, almost all proteins begin with this amino acid. The sequence of nucleotide triplets that follows the start codon signal is termed the reading frame. The codons on mRNA are sequentially recognized by tRNA adaptor proteins. Specific enzymes termed aminoacyl-tRNA synthetases link a specific amino acid to a specific tRNA. The translation of mRNA to
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Surgery_Schwartz_3298
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Surgery_Schwartz
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The codons on mRNA are sequentially recognized by tRNA adaptor proteins. Specific enzymes termed aminoacyl-tRNA synthetases link a specific amino acid to a specific tRNA. The translation of mRNA to protein requires the ribosomal complex to move step-wise along the mRNA until the initiator methionine sequence is identified. In concert with various protein initiator factors, the methionyl-tRNA is positioned on the mRNA and protein synthesis begins. Each new amino acid is added sequentially by the appropriate tRNA in conjunction with proteins called elongation factors. Protein synthesis proceeds in the amino-to-carboxy-terminus direction.The biologic versatility of proteins is astounding. Among many other functions, proteins serve as enzymes that catalyze critical biochemical reactions, carry signals to and from the extracellular environment, and mediate diverse signaling and regulatory functions in the intracellular environment. They also transport ions and various small molecules
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Surgery_Schwartz. The codons on mRNA are sequentially recognized by tRNA adaptor proteins. Specific enzymes termed aminoacyl-tRNA synthetases link a specific amino acid to a specific tRNA. The translation of mRNA to protein requires the ribosomal complex to move step-wise along the mRNA until the initiator methionine sequence is identified. In concert with various protein initiator factors, the methionyl-tRNA is positioned on the mRNA and protein synthesis begins. Each new amino acid is added sequentially by the appropriate tRNA in conjunction with proteins called elongation factors. Protein synthesis proceeds in the amino-to-carboxy-terminus direction.The biologic versatility of proteins is astounding. Among many other functions, proteins serve as enzymes that catalyze critical biochemical reactions, carry signals to and from the extracellular environment, and mediate diverse signaling and regulatory functions in the intracellular environment. They also transport ions and various small molecules
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Surgery_Schwartz_3299
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Surgery_Schwartz
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carry signals to and from the extracellular environment, and mediate diverse signaling and regulatory functions in the intracellular environment. They also transport ions and various small molecules across plasma mem-branes. Proteins make up the key structural components of cells and the extracellular matrix and are responsible for cell motility. The unique functional properties of proteins are largely deter-mined by their structure (Fig. 15-5).Regulation of Gene Expression. The human organism is made up of a myriad of different cell types that, despite their vastly different characteristics, contain the same genetic mate-rial. This cellular diversity is controlled by the genome and is accomplished by tight regulation of gene expression. This leads to the synthesis and accumulation of different complements of RNA and, ultimately, to the proteins found in different cell types. For example, muscle and bone express different genes or the same genes at different times. Moreover, the
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Surgery_Schwartz. carry signals to and from the extracellular environment, and mediate diverse signaling and regulatory functions in the intracellular environment. They also transport ions and various small molecules across plasma mem-branes. Proteins make up the key structural components of cells and the extracellular matrix and are responsible for cell motility. The unique functional properties of proteins are largely deter-mined by their structure (Fig. 15-5).Regulation of Gene Expression. The human organism is made up of a myriad of different cell types that, despite their vastly different characteristics, contain the same genetic mate-rial. This cellular diversity is controlled by the genome and is accomplished by tight regulation of gene expression. This leads to the synthesis and accumulation of different complements of RNA and, ultimately, to the proteins found in different cell types. For example, muscle and bone express different genes or the same genes at different times. Moreover, the
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Surgery_Schwartz_3300
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Surgery_Schwartz
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different complements of RNA and, ultimately, to the proteins found in different cell types. For example, muscle and bone express different genes or the same genes at different times. Moreover, the choice of which genes are expressed in a given cell at a given time depends on signals received from its environment. There are multiple levels at which gene expression can be controlled along the pathway from DNA to RNA to protein (see Fig. 15-4). Transcriptional control refers to the mechanism for regulating when and how often a gene is transcribed. Splicing of the primary RNA tran-script (RNA processing control) and selection of completed Brunicardi_Ch15_p0479-p0510.indd 48418/02/19 11:12 AM 485MOLECULAR BIOLOGY, THE ATOMIC THEORY OF DISEASE, AND PRECISION SURGERYCHAPTER 15Figure 15-5. Maturation of a functional protein. Although the lin-ear amino acid sequence of a protein often is shown, the function of a protein also is controlled by its correctly folded three-dimensional
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Surgery_Schwartz. different complements of RNA and, ultimately, to the proteins found in different cell types. For example, muscle and bone express different genes or the same genes at different times. Moreover, the choice of which genes are expressed in a given cell at a given time depends on signals received from its environment. There are multiple levels at which gene expression can be controlled along the pathway from DNA to RNA to protein (see Fig. 15-4). Transcriptional control refers to the mechanism for regulating when and how often a gene is transcribed. Splicing of the primary RNA tran-script (RNA processing control) and selection of completed Brunicardi_Ch15_p0479-p0510.indd 48418/02/19 11:12 AM 485MOLECULAR BIOLOGY, THE ATOMIC THEORY OF DISEASE, AND PRECISION SURGERYCHAPTER 15Figure 15-5. Maturation of a functional protein. Although the lin-ear amino acid sequence of a protein often is shown, the function of a protein also is controlled by its correctly folded three-dimensional
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Surgery_Schwartz_3301
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Surgery_Schwartz
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15-5. Maturation of a functional protein. Although the lin-ear amino acid sequence of a protein often is shown, the function of a protein also is controlled by its correctly folded three-dimensional structure. In addition, many proteins also have covalent posttransla-tional modifications such as phosphorylation or noncovalent bind-ing to a small molecule or a protein.Unfolded inactive proteinFolded inactive protein Mature inactive proteinBinding proteinPosttranslationalmodification(e.g., phosphorylation)PCofactor bindingmRNAs for nuclear export (RNA transport control) represent additional potential regulatory steps. The mRNAs in the cyto-plasm can be selectively translated by ribosomes (translational control) or selectively stabilized or degraded (mRNA degrada-tion control). Finally, the resulting proteins can undergo selec-tive activation, inactivation, or compartmentalization (protein activity control).Because a large number of genes are regulated at the tran-scriptional level,
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Surgery_Schwartz. 15-5. Maturation of a functional protein. Although the lin-ear amino acid sequence of a protein often is shown, the function of a protein also is controlled by its correctly folded three-dimensional structure. In addition, many proteins also have covalent posttransla-tional modifications such as phosphorylation or noncovalent bind-ing to a small molecule or a protein.Unfolded inactive proteinFolded inactive protein Mature inactive proteinBinding proteinPosttranslationalmodification(e.g., phosphorylation)PCofactor bindingmRNAs for nuclear export (RNA transport control) represent additional potential regulatory steps. The mRNAs in the cyto-plasm can be selectively translated by ribosomes (translational control) or selectively stabilized or degraded (mRNA degrada-tion control). Finally, the resulting proteins can undergo selec-tive activation, inactivation, or compartmentalization (protein activity control).Because a large number of genes are regulated at the tran-scriptional level,
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