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Surgery_Schwartz. requirement, hemodynamic instability, and graft dysfunction from hematoma compression. For recipients on anticoagulation or antiplatelet treatments, the threshold for surgical exploration is lower. Small unligated ves-sels at the donor’s renal hilum or recipient’s retroperitoneum are likely sources of bleeding.One of the most devastating postoperative complications in kidney recipients is graft thrombosis. It is rare, occurring in fewer than 1% of recipients. The recipient risk factors include a history of recipient hypercoagulopathy and severe peripheral vascular disease; donor-related risk factors include the use of en bloc or pediatric donor kidneys, procurement damage, techni-cal factors such as intimal dissection or torsion of vessels, and hyperacute rejection. Graft thrombosis usually occurs within the first several days posttransplant. Acute cessation of urine output in recipients with brittle posttransplant diuresis and the sudden onset of hematuria or graft pain should arouse


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Surgery_Schwartz. occurs within the first several days posttransplant. Acute cessation of urine output in recipients with brittle posttransplant diuresis and the sudden onset of hematuria or graft pain should arouse suspicion of graft thrombosis. Doppler ultrasound may help confirm the diagnosis. In cases of graft thrombosis, an urgent thrombectomy is indi-cated; however, it rarely results in graft salvage.Urologic complications are seen in up to 5% of recipi-ents. The cause is often related to ureteral ischemia, damage during procurement of the donor’s distal ureter, or technical errors. Symptoms of urine leak include fever, pain, swelling at the graft site, increased creatinine level, decreased urine output, and cutaneous urinary drainage. Diagnosis can be confirmed by a combination of ultrasound, nuclear renography, drainage of perinephric fluid collection, and comparison of serum and fluid creatinine levels. Depending on the location and volume of the urine leak, satisfactory results can be


Surgery_Schwartz

Surgery_Schwartz. nuclear renography, drainage of perinephric fluid collection, and comparison of serum and fluid creatinine levels. Depending on the location and volume of the urine leak, satisfactory results can be achieved by surgi-cal exploration and repair or by percutaneous placement of a nephrostomy and ureteral stenting.Early urinary obstruction can be due to edema, blood clots, torsion of the ureter, or compression from a hematoma. Late urinary obstruction is often related to ischemia. The appear-ance of hydronephrosis on ultrasound is a good initial indicator. Treatment includes percutaneous placement of a nephrostomy and ureteral stenting. If transluminal intervention fails, surgical intervention (such as ureteral reimplantation or a ureteropyelos-tomy) can be undertaken.ResultsA kidney transplant remains the most common solid organ transplant in the world today. With the introduction of induc-tion immunosuppressive therapy and ever-improving, less toxic immunosuppressive medications,


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Surgery_Schwartz. remains the most common solid organ transplant in the world today. With the introduction of induc-tion immunosuppressive therapy and ever-improving, less toxic immunosuppressive medications, posttransplant outcomes have become better and better. And, as noted above, posttransplant outcomes have continued to improve: in 2014 allograft and patient survival rates were well over 90%, and in 2015, the 1-year graft survival rate with a living donor kidney was nearly Brunicardi_Ch11_p0355-p0396.indd 37301/03/19 6:54 PM 374BASIC CONSIDERATIONSPART I98%; with a deceased donor kidney, the rate was approximately 95%.71,89The biggest improvements have been in the reduction of 1-year graft failure. With a deceased donor kidney, the 1-year graft failure rate dropped from approximately 20% in 1989 to less than 7% in 2009 to 4.8% in 2015; with a living donor kidney, the rate dropped from 8.5% in 1989 to less than 3% in 2015.89 Furthermore, steroid-free protocols90 and calcineurin-free


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Surgery_Schwartz. in 1989 to less than 7% in 2009 to 4.8% in 2015; with a living donor kidney, the rate dropped from 8.5% in 1989 to less than 3% in 2015.89 Furthermore, steroid-free protocols90 and calcineurin-free protocols91 have been validated and implemented in the last several decades, further reducing medication-related side effects and vastly improving the quality of life for tens of thousands of recipients.Currently, the most common cause of graft loss is recipi-ent death (usually from cardiovascular causes) with a function-ing graft. The second most common cause is chronic allograft nephropathy; characterized by a slow, unrelenting deterioration of graft function, it likely has multiple causes (both immuno-logic and nonimmunologic).92,93 The graft failure rate due to complications related to surgical technique has remained at about 1% to 2%.PANCREAS TRANSPLANTATIONA successful pancreas transplant currently is the only definitive long-term treatment for patients with insulin-dependent


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Surgery_Schwartz. to surgical technique has remained at about 1% to 2%.PANCREAS TRANSPLANTATIONA successful pancreas transplant currently is the only definitive long-term treatment for patients with insulin-dependent diabetes mellitus (IDDM) that (a) restores normal glucose hemostasis without exposing patients to the risk of severe hypoglycemia and (b) prevents, halts, or, in some cases, reverses the development or progression of secondary complications of diabetes.94Given its vast medical, social, and financial implications, diabetes mellitus is a huge burden to patients and to society as a whole. An estimated 10% to 15% of the U.S. population is affected by it; of all diabetic patients, 10% have early-onset dis-ease. In the United States, diabetes mellitus is the most common cause of end-stage kidney disease, blindness, impotence, major limb amputations, and coronary or peripheral vascular bypass procedures. It is one of the most common causes of death, along with myocardial infarction and stroke.


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Surgery_Schwartz. blindness, impotence, major limb amputations, and coronary or peripheral vascular bypass procedures. It is one of the most common causes of death, along with myocardial infarction and stroke. Diabetes significantly decreases not only the quality of life but also life expectancy.Despite improvements in exogenous insulin administra-tion (including the use of devices such as insulin pumps), wide fluctuations in glucose levels and the risk of hypoglycemic epi-sodes are common. The Diabetes Control and Complications Trial (DCCT) demonstrated in the late 1990s that intensive insulin therapy may slow the rate of secondary complications of diabetes—yet at the expense of (life-threatening) iatrogenic hypoglycemia. The annual mortality rate of patients with insu-lin-induced inadvertent hypoglycemia is estimated to be as high as 2% to 3%.Since the first pancreas transplant in December 1966, per-formed by William Kelly and Richard Lillehei at the Univer-sity of Minnesota, more than 25,000


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Surgery_Schwartz. is estimated to be as high as 2% to 3%.Since the first pancreas transplant in December 1966, per-formed by William Kelly and Richard Lillehei at the Univer-sity of Minnesota, more than 25,000 pancreas transplants in the United States and more than 10,000 pancreas transplants from all over the world have been reported to the International Pan-creas Transplant Registry (IPTR).94,95Pancreas transplants are performed in three recipient categories:• Simultaneous pancreas and kidney (SPK) transplant in diabetic and uremic patients. Almost 80% of pancreas trans-plants are performed in this category. The recipient is already 5obligated to lifelong immunosuppressive therapy, due to the need for a kidney transplant, so only the surgical risk of a pancreas transplant is added. A successful SPK transplant renders the recipient dialysis-free and insulin-independent.• Pancreas after kidney (PAK) transplant in diabetic and posturemic patients. Approximately 15% of all pancreas trans-plants fall


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Surgery_Schwartz. renders the recipient dialysis-free and insulin-independent.• Pancreas after kidney (PAK) transplant in diabetic and posturemic patients. Approximately 15% of all pancreas trans-plants fall into this category. These patients previously under-went a kidney transplant with either a living or deceased donor, but are candidates for a subsequent pancreas transplant because of poor glucose control or because of progression of secondary diabetic complications (which may include the development of diabetic nephropathy in the transplanted kidney).• Pancreas transplant alone (PTA) in nonuremic patients with brittle diabetes mellitus. Only about 5% of all pancreas trans-plants are in this category. These patients have not yet devel-oped advanced diabetic nephropathy, but their glucose levels are extremely labile despite best efforts of control. Because of the lifelong need for immunosuppressive therapy, the sur-gical risk has to be balanced with the medical risks of brittle diabetes (e.g.,


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Surgery_Schwartz. extremely labile despite best efforts of control. Because of the lifelong need for immunosuppressive therapy, the sur-gical risk has to be balanced with the medical risks of brittle diabetes (e.g., frequent episodes of hypoglycemia and hypo-glycemic unawareness).In SPK recipients, a plethora of literature exists that demonstrates significant improvements in secondary dia-betic complications (across all organ systems) posttransplant. Improvements have been reported in diabetic nephropathy, neu-ropathy (autonomic and peripheral), microand macrovascular disease, retinopathy, gastroparesis, and other secondary com-plications.96 Currently, more than 1000 pancreas transplants are performed annually in the United States, with the goal of confer-ring the following benefits: excellent glucose control (similar to that of a functioning native pancreas), prevention or improve-ment of secondary diabetic complications, and increased quality of life and life expectancy. In addition, pancreas


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Surgery_Schwartz. control (similar to that of a functioning native pancreas), prevention or improve-ment of secondary diabetic complications, and increased quality of life and life expectancy. In addition, pancreas transplants can be successfully performed in patients who have undergone a total pancreatectomy for benign disease (such as chronic pan-creatitis) to treat both endocrine and exocrine deficiency after surgery.97Donor OperationThe general criteria for selecting deceased donors for pancreas procurement are similar to those for other solid organs; a history of type 1 diabetes mellitus obviously is a contraindication. Rela-tive contraindications include previous pancreatic procedure(s), as well as pancreatic disorders, such as chronic pancreatitis and intraductal papillary mucinous neoplasm. Hyperglycemia in itself is not a contraindication to pancreas procurement because its cause in brain-dead donors usually is severe insulin resis-tance, which is rarely observed in recipients.In light of


Surgery_Schwartz

Surgery_Schwartz. in itself is not a contraindication to pancreas procurement because its cause in brain-dead donors usually is severe insulin resis-tance, which is rarely observed in recipients.In light of better anatomic understanding and improved surgical skills, all three abdominal organs that share a common blood supply (pancreas, liver, and intestine) can be procured at the same time and transplanted into three different recipi-ents (Fig. 11-10). During pancreas procurement, a “no-touch” technique of the gland is preferred; dissection of the pancreas is carried out in a way that avoids direct manipulation of the organ such that simultaneous procurement of the spleen, duodenum, and surrounding connective tissues occurs.In contrast to the liver and kidneys, the pancreas should not be extensively flushed at the end of the procurement. To minimize the amount of preservation fluid that reaches the pan-creas, the splenic artery and SMA can be temporarily clamped Brunicardi_Ch11_p0355-p0396.indd


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Surgery_Schwartz. at the end of the procurement. To minimize the amount of preservation fluid that reaches the pan-creas, the splenic artery and SMA can be temporarily clamped Brunicardi_Ch11_p0355-p0396.indd 37401/03/19 6:54 PM 375TRANSPLANTATIONCHAPTER 11MHVLHVRHVIPDAMCARCAFigure 11-10. Simultaneous pancreas, in situ split-liver, and intestine procurement. IPDA = inferior pancreaticoduodenal artery; LHV = left hepatic vein; MCA = middle cerebral artery; MHV = middle hepatic vein; RCA = right coro-nary artery; RHV= right hepatic vein. (Repro-duced from Gruessner RWG, Sutherland DER: Transplantation of the Pancreas. New York, NY: Springer, 2004.)at their origin from the aorta. Usually, the celiac axis with an aortic Carrel patch is retained with the liver. The splenic artery is divided close to its origin and is retained with the pancreas. The SMA is also procured with an aortic Carrel patch and is retained with the pancreas.In case of a replaced or aberrant right hepatic artery, this first branch


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Surgery_Schwartz. and is retained with the pancreas. The SMA is also procured with an aortic Carrel patch and is retained with the pancreas.In case of a replaced or aberrant right hepatic artery, this first branch off of the SMA is carefully dissected out from the posterior surface of the pancreas. A replaced or aberrant right hepatic artery does not transverse the pancreas and is not a con-traindication to combined pancreas and liver procurement. But with this anatomic variant, an aortic Carrel patch with the proxi-mal SMA and replaced or aberrant right hepatic artery remains with the liver; the distal SMA with the inferior pancreaticoduo-denal artery remains with the pancreas.In the relatively rare event that the liver is not procured, then neither the splenic nor the gastroduodenal arteries need to be divided at their respective takeoff; the donor’s celiac axis and the SMA are included on a common Carrel patch. This tech-nique allows a single arterial anastomosis to be performed in the recipient


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Surgery_Schwartz. divided at their respective takeoff; the donor’s celiac axis and the SMA are included on a common Carrel patch. This tech-nique allows a single arterial anastomosis to be performed in the recipient without reconstruction. At the end of the procurement, the pancreas is attached to the spleen, duodenum, and proximal jejunum, which is stapled at both ends.98Back Table Preparation of the Pancreas GraftBack table preparation of the pancreas graft consists of four steps: (a) removal of the spleen; (b) shortening, restapling, and/or suture reinforcement of the mesenteric root; (c) trimming of any excess distal and proximal duodenum, along with reinforce-ment of the proximal staple line; and (d) arterial reconstruction.Back table preparation is carried out in a basin filled with chilled preservation solution. The most common tech-nique to create a single arterial inflow to the pancreas graft is the “Y-graft” reconstruction, using a resected segment of the donor iliac artery bifurcation. In


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Surgery_Schwartz. solution. The most common tech-nique to create a single arterial inflow to the pancreas graft is the “Y-graft” reconstruction, using a resected segment of the donor iliac artery bifurcation. In this technique, the donor exter-nal iliac artery is anastomosed end-to-end to the donor SMA, and the donor internal iliac artery is anastomosed end-to-end to the splenic artery (Fig. 11-11). This procedure allows the donor common iliac artery to be anastomosed as a single vessel to the recipient’s common iliac artery. For venous outflow, the portal vein is kept relatively short, in order to avoid the risk of venous thrombosis by kinking or impingement.98Recipient OperationOver the years, different surgical techniques have been described for (a) the management of exocrine pancreatic secretions and (b) the type of venous drainage. For the secretions, the two most common techniques are drainage of the duodenal segment to the bladder (bladder drainage) or to the small bowel (enteric drain-age)


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Surgery_Schwartz. (b) the type of venous drainage. For the secretions, the two most common techniques are drainage of the duodenal segment to the bladder (bladder drainage) or to the small bowel (enteric drain-age) (Figs. 11-12 and 11-13). For venous drainage, systemic venous drainage is preferred over portal venous drainage.The pancreas graft is usually placed intra-abdominally and preferably on the right side because the iliac vessels are Brunicardi_Ch11_p0355-p0396.indd 37501/03/19 6:54 PM 376BASIC CONSIDERATIONSPART IFigure 11-11. Posterior view of the pancreas graft with Y-graft reconstruction. EIA = external iliac artery; IIA = internal iliac artery; SA = splenic artery; SMA = superior mesenteric artery. (Reproduced from Gruessner RWG, Sutherland DER: Transplanta-tion of the Pancreas. New York, NY: Springer, 2004.)Figure 11-12. Whole-organ transplant with systemic vein and bladder exocrine drainage. (Reproduced from Gruessner RWG, Sutherland DER: Transplantation of the Pancreas. New York, NY:


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Surgery_Schwartz. Springer, 2004.)Figure 11-12. Whole-organ transplant with systemic vein and bladder exocrine drainage. (Reproduced from Gruessner RWG, Sutherland DER: Transplantation of the Pancreas. New York, NY: Springer, 2004.)SAIIAEIASMASMAin a more shallow position on the right than on the left side; moreover, the vessels are already appropriately aligned for the vascular anastomoses (i.e., a lateral position for the com-mon iliac vein, a medial position for the common iliac artery). Venous and arterial anastomoses are performed end-to-side. After restoration of blood flow to the graft, hemostasis must be meticulously maintained. Because the donor portal vein pur-posely is kept short, ligation and transection of all of the recipi-ent’s internal iliac vein branches are frequently performed in order to prevent tension on the venous anastomosis. The pan-creas usually is placed with the pancreatic head and duodenum pointing caudally.Bladder drainage is performed using either a hand-sewn or a stapled


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Surgery_Schwartz. prevent tension on the venous anastomosis. The pan-creas usually is placed with the pancreatic head and duodenum pointing caudally.Bladder drainage is performed using either a hand-sewn or a stapled anastomosis in which the antimesenteric side of the donor duodenum is sewn to the superior portion of the dome of the bladder. The stapled technique requires that a circular cut-ting stapler be inserted through the open distal end of the donor duodenum, which is subsequently closed. Bladder drainage has two main advantages. First, rejection of the exocrine pancreas precedes rejection of the endocrine pancreas by 5 to 7 days. Amylase levels are measured routinely in the recipient’s urine. With bladder drainage, antirejection treatment can successfully be implemented when the recipient is still normoglycemic and only hypoamylasuric. In the absence of hyperglycemia, more than 90% of pancreas rejection episodes are reversible. Second, bladder drainage avoids the bacterial contamination that


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Surgery_Schwartz. normoglycemic and only hypoamylasuric. In the absence of hyperglycemia, more than 90% of pancreas rejection episodes are reversible. Second, bladder drainage avoids the bacterial contamination that occurs with enteric drainage. If an anastomotic leak occurs, it is easier to treat because the infection usually remains localized to the right lower quadrant.Enteric drainage is more physiologic and has advantages as well. The antimesenteric side of the donor’s duodenum is anastomosed to the antimesenteric portion of the recipient’s jejunum in a side-to-side fashion. The enteric anastomosis can also involve a defunctionalized Roux-en-Y loop, which mini-mizes the potential complications if an enteric leak occurs.98 Currently, in the United States, more than 80% of all pancreas transplants are performed with enteric drainage for the exocrine pancreatic secretions, and more than 90% employ systemic venous drainage.95Brunicardi_Ch11_p0355-p0396.indd 37601/03/19 6:54 PM


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Surgery_Schwartz. transplants are performed with enteric drainage for the exocrine pancreatic secretions, and more than 90% employ systemic venous drainage.95Brunicardi_Ch11_p0355-p0396.indd 37601/03/19 6:54 PM 377TRANSPLANTATIONCHAPTER 11Figure 11-13. Whole-organ transplant with systemic vein and enteric exocrine drainage. (Reproduced from Gruessner RWG, Sutherland DER: Transplantation of the Pancreas. New York, NY: Springer, 2004.)ComplicationsThe technical complication rate for pancreas transplants is higher than for any other solid organ transplant. Four fac-tors contribute to the high surgical complication rate99: (a) the nature of the organ itself with inherent organ-specific surgical complications (e.g., pancreatitis, abscesses, necrosis, fistulas, and pseudocysts) and its low blood flow (which significantly increases the risk of thrombosis, as compared with a kidney or liver transplant); (b) the risk of a leak or infection after con-necting two hollow viscera (the duodenum and either the


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Surgery_Schwartz. significantly increases the risk of thrombosis, as compared with a kidney or liver transplant); (b) the risk of a leak or infection after con-necting two hollow viscera (the duodenum and either the blad-der or small intestine); (c) the increased incidence of rejection episodes because the pancreas is one of the most immunogenic solid organs; and (d) the underlying disease of diabetes mellitus, predisposing patients not only to infections but also to cardio-vascular and other complications.The most common surgical complications are throm-bosis (an incidence of 5%–15%), intra-abdominal abscesses (5%–10%), and bleeding (6%–8%). Other pancreas-specific complications include graft pancreatitis (frequently due to pro-curement or reperfusion injury), pancreatic fistulas, and pan-creatic pseudocysts. Anastomotic leaks do not always require a graft pancreatectomy, but arterial pseudoaneurysms, arteriove-nous fistulas, and wound dehiscence may. Bleeding frequently requires


Surgery_Schwartz

Surgery_Schwartz. pan-creatic pseudocysts. Anastomotic leaks do not always require a graft pancreatectomy, but arterial pseudoaneurysms, arteriove-nous fistulas, and wound dehiscence may. Bleeding frequently requires relaparotomy.Thrombosis usually occurs within the first week posttrans-plant. It manifests as a sudden increase in insulin requirements or as a sharp drop in urinary amylase levels. Venous thrombosis, which is more common than arterial thrombosis, is associated with distinct clinical symptoms, including a swollen and tender graft, hematuria, lower extremity edema, and deep vein throm-bosis, the latter two occurring ipsilaterally. Arterial thrombosis is less symptomatic and may not initially cause pain; its diag-nosis is usually confirmed by Doppler ultrasonography. Surgi-cal exploration in recipients with thrombosis usually requires a graft pancreatectomy.With the advent of advanced interventional radiologic procedures to drain intra-abdominal abscesses, the reoperation rate has markedly


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Surgery_Schwartz. with thrombosis usually requires a graft pancreatectomy.With the advent of advanced interventional radiologic procedures to drain intra-abdominal abscesses, the reoperation rate has markedly decreased. Pancreas transplant recipients are usually kept on broad-spectrum antimicrobial agents for the first 7 days posttransplant.The most common nonsurgical complication posttrans-plant is rejection. The incidence of rejection is about 30% within the first year. The diagnosis is usually based on an increase in serum amylase and lipase levels and, in bladder-drained recipi-ents, a decrease in urinary amylase levels. A sustained drop in urinary amylase levels greater than 25% from baseline should prompt a pancreas graft biopsy to rule out rejection. In enteric-drained recipients, one must rely on serum amylase and lipase levels only. Other signs and symptoms of rejection include tenderness over the graft, unexplained fever, and hyperglyce-mia, which usually is a late finding; fewer than 5% of


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Surgery_Schwartz. serum amylase and lipase levels only. Other signs and symptoms of rejection include tenderness over the graft, unexplained fever, and hyperglyce-mia, which usually is a late finding; fewer than 5% of all rejec-tion episodes can be reversed in its presence. The diagnosis of rejection should be confirmed by a percutaneous pancreas graft biopsy.Other nonsurgical complications include infections with CMV, HCV, or extra-abdominal bacteria or fungi; malignan-cies, such as PTLD; and, rarely, graft-versus-host disease. For such complications, the diagnosis and treatment are similar to what is recommended after other solid organ transplants.Bladder-drained pancreas recipients may experience an array of unique urologic complications. Usually the result of the irritating nature of pancreatic enzymes on the urothelium in the bladder and urethra, these urologic complications can lead to cystitis, hematuria, and dysuria. With the loss of bicarbonate from pancreatic secretions, dehydration and


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Surgery_Schwartz. on the urothelium in the bladder and urethra, these urologic complications can lead to cystitis, hematuria, and dysuria. With the loss of bicarbonate from pancreatic secretions, dehydration and metabolic acidosis are not uncommon. Many of these complications are chronic, such that approximately 20% to 30% of all bladder-drained recipients require conversion to enteric drainage within the first 5 years posttransplant.100Living Donor Pancreas TransplantsPancreas transplants using living donors also can be performed safely and successfully in select donors and recipients. Since 1979, about 150 such transplants have been performed world-wide, with 1-year graft survival rates in excess of 85% over the last decade. A meticulous donor evaluation using standard criteria remains key to a low donor metabolic and surgical com-plication rate. The concept of procuring the distal pancreas from a living donor is based on the observation that patients with benign or malignant pancreatic disorders can


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Surgery_Schwartz. metabolic and surgical com-plication rate. The concept of procuring the distal pancreas from a living donor is based on the observation that patients with benign or malignant pancreatic disorders can undergo a distal hemipancreatectomy without any serious change in endocrine function.Living donor pancreas transplants are ideal for patients with an identical twin, but other relatives can be suitable donors as well. In particular, patients with high PRA levels should be considered for a living donor transplant.Living donor pancreas transplants decrease the number of deaths of diabetic patients on the waiting list, help overcome the organ shortage, reduce mortality and morbidity, and improve the quality of life for patients with debilitating side effects of diabetes. The use of living donors also reduces the risk of graft rejection, as compared with the use of deceased donors. Yet living donor pancreas transplants remain relatively rare, per-formed under very selective circumstances. In


Surgery_Schwartz

Surgery_Schwartz. also reduces the risk of graft rejection, as compared with the use of deceased donors. Yet living donor pancreas transplants remain relatively rare, per-formed under very selective circumstances. In terms of surgical technique, the donor splenic artery and vein are anastomosed to the recipient’s external iliac artery and vein in an end-to-side fashion, and exocrine drainage can occur via an anastomosis Brunicardi_Ch11_p0355-p0396.indd 37701/03/19 6:54 PM 378BASIC CONSIDERATIONSPART IFigure 11-14. Segmental transplant with systemic vein and blad-der exocrine drainage. The donor splenic artery and splenic vein are anastomosed end-to-side to the recipient’s external iliac artery and vein. The splenic artery anastomosis is lateral and proximal to the splenic vein anastomosis. A two-layer ductocystostomy is constructed. (Reproduced from Gruessner RWG, Sutherland DER: Transplantation of the Pancreas. New York, NY: Springer, 2004.)of the pancreatic duct and transected end of the pancreas


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Surgery_Schwartz. is constructed. (Reproduced from Gruessner RWG, Sutherland DER: Transplantation of the Pancreas. New York, NY: Springer, 2004.)of the pancreatic duct and transected end of the pancreas to the bladder or bowel101 (Fig. 11-14).ResultsAs of December 2010, more than 35,000 pancreas transplants had been reported to the IPTR: more than 25,000 transplants in the United States and more than 10,000 in other countries. According to IPTR data, recipient age at the time of the trans-plant has increased significantly, and so has the number of trans-plants for patients with type 2 diabetes. The trend over time has been toward stricter donor criteria, with a concentration on younger donors, preferably trauma victims, and on short pan-creas graft preservation time.Drainage techniques have changed over time, too: enteric drainage of exocrine pancreatic secretions is now predominant, in combination with systemic drainage of the venous effluent of the pancreas graft. Immunosuppressive protocols have


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Surgery_Schwartz. time, too: enteric drainage of exocrine pancreatic secretions is now predominant, in combination with systemic drainage of the venous effluent of the pancreas graft. Immunosuppressive protocols have devel-oped toward antibody induction therapy, followed by administra-tion of tacrolimus and MMF for maintenance. Steroid avoidance has increased over time in all three recipient categories.Between 2005 and 2009 and 2010 and 2014, the num-ber of U.S. pancreas transplants declined by over 20%, while the overall number of pancreas transplants performed outside the United States has increased. The decline in U.S. numbers is predominantly due to the decline in primary and secondary pancreas after kidney transplants (PAK). During the time period studied, the number of PAK transplants dropped by 50%. In contrast, the number of simultaneous pancreas/kidney trans-plants (SPK) declined by only 10%, and the number of pan-creas transplants alone (PTA) by 20%. Over 90% of pancreas transplants worldwide


Surgery_Schwartz

Surgery_Schwartz. In contrast, the number of simultaneous pancreas/kidney trans-plants (SPK) declined by only 10%, and the number of pan-creas transplants alone (PTA) by 20%. Over 90% of pancreas transplants worldwide were performed, with a simultaneous kidney transplant and excellent results. Transplant outcomes in SPK improved significantly because of a decrease in the rates of technical and immunologic graft loss. In 2010 to 2014 vs. 2005 to 2009, U.S. SPK transplant patient survival at 1 year posttransplant increased from 95.7% to 97.4%, pancreas graft function increased from 88.3% to 91.3%, and kidney func-tion increased from 93.6% to 95.5%. A significant improve-ment was also noted in PAK transplants. One-year patient survival increased from 96.4% to 97.9%, and pancreas graft function increased from 81.0% to 86.0%. PTA 1-year patient survival remained constant at 97%, and pancreas 1-year graft survival improved from 81.0% to 85.7%. IPTR data show sig-nificant improvements in patient survival and


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Surgery_Schwartz. 81.0% to 86.0%. PTA 1-year patient survival remained constant at 97%, and pancreas 1-year graft survival improved from 81.0% to 85.7%. IPTR data show sig-nificant improvements in patient survival and pancreas graft function rates since the inception of UNOS, over a course of 24 years.92,95,99,102 Clearly, pancreas transplants now offer excel-lent outcomes for patients with IDDM.Islet versus Pancreas TransplantsPancreas transplants are frequently compared with islet trans-plants (vide infra), which are less invasive and, therefore, more appealing. It is important to emphasize that these two types of transplants are not mutually exclusive but rather complementary. The results of islet transplants have improved over the past decade, but overall islet graft function, specifically long-term function, still significantly trails overall pancreas graft function.103 Islet transplants involve pancreas procurement (as described earlier) and then separation of islets from the exocrine


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Surgery_Schwartz. function, still significantly trails overall pancreas graft function.103 Islet transplants involve pancreas procurement (as described earlier) and then separation of islets from the exocrine pan-creatic tissues using proteolytic enzymes (as described later). The human pancreas contains about one million islets, of which half are lost during the isolation process. About 10,000 islets per kilo-gram of body weight are needed to achieve insulin independence when transplanted into the liver. Frequently, one donor pancreas does not suffice; in fact, up to four donor pancreases have been used for one islet recipient.Because of the relatively disappointing long-term out-comes, insurance providers in the United States do not provide reimbursement for islet transplants. Transplant centers with both pancreas and islet transplant programs follow an algorithm that favors islet transplants in patients with a high surgical risk and pancreas transplants in patients with a low surgical risk. Although


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Surgery_Schwartz. pancreas and islet transplant programs follow an algorithm that favors islet transplants in patients with a high surgical risk and pancreas transplants in patients with a low surgical risk. Although solitary donor pancreases are not in short supply, only one donor pancreas is required for a successful pancreas transplant; in con-trast, two to four donor pancreases are commonly used for one islet recipient with less favorable long-term outcomes.Of note, the primary goal of current islet transplant trials is not insulin independence but rather a reduction in the inci-dence and severity of hypoglycemic events, a reduction in exog-enous insulin requirements, and an amelioration of hemoglobin A1c levels. Islet transplants rarely maintain long-term insulin independence. A recent study showed a higher rate of insulin independence in PTA recipients than in recipients of an islet transplant alone, despite the use of up to three donor pancreases in each of the islet recipients.104 Until islet


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Surgery_Schwartz. higher rate of insulin independence in PTA recipients than in recipients of an islet transplant alone, despite the use of up to three donor pancreases in each of the islet recipients.104 Until islet transplant results sig-nificantly improve and include long-term insulin independence, a pancreas transplant remains the treatment of choice for β-cell replacement therapy in patients with IDDM.ISLET TRANSPLANTATIONTransplanting islets of Langerhans isolated from deceased donor pancreases is an appealing option for patients with type 1 diabetes. An islet transplant involves the procurement of a 6Brunicardi_Ch11_p0355-p0396.indd 37801/03/19 6:54 PM 379TRANSPLANTATIONCHAPTER 11donor pancreas and its transportation to a specialized islet iso-lation facility, where the pancreas is enzymatically digested; then, the islets are purified from the rest of the digested pan-creas using density gradients. The purified islets are then cul-tured and evaluated for their identity, viability, and


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Surgery_Schwartz. digested; then, the islets are purified from the rest of the digested pan-creas using density gradients. The purified islets are then cul-tured and evaluated for their identity, viability, and potency, before being infused into the portal vein of a diabetic recipient. When the procedure is successful, these islet cells engraft into the recipient and secrete insulin, providing excellent moment-to-moment control of blood glucose, as is seen with a whole-pancreas transplant.A successful islet transplant offers advantages over exog-enous insulin injections—advantages that are similar to those of a whole-pancreas transplant. These advantages include restor-ing β-cell secretory capacity, improving glucose counterregula-tion, restoring hypoglycemia awareness, providing perfect or near-perfect glucose homeostasis, and, potentially, preventing secondary diabetic complications.Unlike a whole-pancreas transplant, an islet transplant does not involve a major surgical procedure with its associated


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Surgery_Schwartz. homeostasis, and, potentially, preventing secondary diabetic complications.Unlike a whole-pancreas transplant, an islet transplant does not involve a major surgical procedure with its associated mortality and morbidity. Instead, it can generally be performed as an outpatient procedure using percutaneous catheter-based therapy to cannulate a branch of the portal vein, with minimal recovery time for the recipient. Potential complications associ-ated with islet injection include portal hypertension, portal vein thrombosis, hepatic abscesses, and bacteremia. Theoretically, islet transplants could have wider application (as compared with current practice and with whole-pancreas transplants), given the significantly lower surgical risk, the relatively small tissue vol-ume transplanted, and the potential for islet immunomodula-tion or immunoisolation, which could minimize or eliminate the need for immunosuppression.The first reported attempt at an islet transplant was in 1893 by


Surgery_Schwartz

Surgery_Schwartz. and the potential for islet immunomodula-tion or immunoisolation, which could minimize or eliminate the need for immunosuppression.The first reported attempt at an islet transplant was in 1893 by Watson-Williams and Harsant: they transplanted a sheep’s minced pancreas into the subcutaneous tissue of a young boy with ketoacidosis.105 The discovery of insulin may have reduced interest in islet transplants as a treatment for diabetes, at least until the realization that insulin could not provide perfect glyce-mic control and that, therefore, patients ultimately suffered dev-astating secondary complications. Several milestones ensued: the first whole-pancreas transplants,106 early success with rodent islet transplants,107 and then, in the 1970s, human islet autotrans-plants after pancreatectomy, in order to address the intractable pain associated with chronic pancreatitis, by Sutherland, Najarian, and colleagues in Minnesota.108Until recently, attempts to extend those trailblazing


Surgery_Schwartz

Surgery_Schwartz. in order to address the intractable pain associated with chronic pancreatitis, by Sutherland, Najarian, and colleagues in Minnesota.108Until recently, attempts to extend those trailblazing find-ings of clinical islet autotransplants to clinical islet allotrans-plants in patients with type 1 diabetes met with generally very poor success. For example, in 1995, a report of the International Islet Transplant Registry indicated that of 270 recipients, only 5% were insulin-independent at 1 year posttransplant.In 2000, Shapiro and colleagues reported the results of the Edmonton protocol, which enabled consistent diabetes rever-sal and short-term (<1 year) insulin independence.109-111 The Edmonton protocol prescribed transplanting a large number of freshly isolated islets (>10,000 islet equivalents per kilogram body weight, typically requiring the use of two to four pan-creases) with a specialized “islet-sparing,” steroid-free immu-nosuppressive protocol consisting of low-dose tacrolimus,


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Surgery_Schwartz. per kilogram body weight, typically requiring the use of two to four pan-creases) with a specialized “islet-sparing,” steroid-free immu-nosuppressive protocol consisting of low-dose tacrolimus, sirolimus, and IL-2 receptor antibody induction. Those results were replicated at other experienced transplant centers,112,113 but the rates of long-term (>5 year) insulin independence remained poor, well below those of whole-pancreas transplants.114 Still, despite the low rates of long-term insulin independence, most islet recipients were C-peptide positive and retained hypoglycemia awareness, indicating residual islet function and benefit. In fact, at 9 years posttransplant, 15% remained insulin-independent, and 73% had hypoglycemia awareness and corrected hemoglo-bin A1c levels.115In the mid-2000s, new trials began with the goal of estab-lishing protocols that enable insulin independence, using islets from a single donor pancreas; the results were good, especially with strict donor and


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Surgery_Schwartz. new trials began with the goal of estab-lishing protocols that enable insulin independence, using islets from a single donor pancreas; the results were good, especially with strict donor and recipient selection.116,117 In the most expe-rienced centers, long-term rates of diabetes reversal are now about 50% at 5 years posttransplant. The reasons include refine-ments in pancreas preservation, islet isolation, and culture pro-tocols, as well as the use of newer induction immunosuppressive agent combinations, such as a T-cell–depleting antibody (anti-CD3 antibody, alemtuzumab, or antithymocyte globulin) and a tumor necrosis factor-alpha (TNF-α) inhibitor (etanercept or infliximab). Presumably, viable β-cell mass is now preserved, both preand posttransplant.116-120 Thus, islet transplant results are approaching those of whole-pancreas transplants; however, because islets from more than one pancreas are typically needed, those results cannot be directly compared with the results of


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Surgery_Schwartz. results are approaching those of whole-pancreas transplants; however, because islets from more than one pancreas are typically needed, those results cannot be directly compared with the results of whole-pancreas transplants.121,122In the United States, an islet transplant is still officially deemed an experimental procedure. In contrast, since 2001, it has been considered a standard of care and is fully reimbursed in Canada and, more recently, in the United Kingdom, Sweden, Switzerland, France, and Italy as well.118 The full potential of islet transplants remains to be realized, but the future is excit-ing. As the latest improvements in pancreas preservation, islet isolation and purification, islet culture, and islet immunoiso-lation are implemented clinically, the hope is that sustained insulin independence may become consistently possible with a single pancreas donor and without the need for systemic immunosuppression.LIVER TRANSPLANTATIONThe first attempts at liver transplants in


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Surgery_Schwartz. insulin independence may become consistently possible with a single pancreas donor and without the need for systemic immunosuppression.LIVER TRANSPLANTATIONThe first attempts at liver transplants in the late 1960s through the 1980s were largely experimental endeavors, with a 1-year survival rate of only 30%. But breakthroughs in immunosup-pression, surgical technique, organ preservation, anesthesia, and critical care have improved that rate to approximately 85% today. Liver transplants remain daunting, especially in the face of an organ shortage that results in sicker potential candidates. Unfortunately, the perioperative mortality rate and the 1-year mortality rate are among the highest of any surgical operation currently performed.HistoryThe first experimental liver transplants in dogs are often attrib-uted to C. Stuart Welch in 1955 and then Jack Cannon in 1956. However, current scholarship reveals that Vittorio Staudacher first described the technique in 1952.123 A series of


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Surgery_Schwartz. dogs are often attrib-uted to C. Stuart Welch in 1955 and then Jack Cannon in 1956. However, current scholarship reveals that Vittorio Staudacher first described the technique in 1952.123 A series of canine experiments followed, which refined the surgical technique to ensure perioperative survival.The next obstacle—immunologic rejection—was addressed by drug immunosuppression with AZA and predni-sone. The first human liver transplant trials started in 1963 with Thomas Starzl, but a series of deaths led to a voluntary morato-rium for 3.5 years. With the resumption of clinical transplants in 1967, Starzl performed the first successful liver transplant. Brunicardi_Ch11_p0355-p0396.indd 37901/03/19 6:54 PM 380BASIC CONSIDERATIONSPART IStill, for the next decade, survival rates were dismal: only 20% of the 170 liver transplant recipients in Starzl’s program at the University of Colorado survived more than 5 years.124Several innovations dramatically improved outcomes. The advent of


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Surgery_Schwartz. only 20% of the 170 liver transplant recipients in Starzl’s program at the University of Colorado survived more than 5 years.124Several innovations dramatically improved outcomes. The advent of better immunosuppressive drugs was instrumental. In 1978, cyclosporine was introduced clinically in England. It was soon combined with prednisone to great effect. The arrival of tacrolimus in the 1990s further improved graft survival.Technical advances were also significant. Donor procure-ment techniques and cold organ preservation protocols were standardized, and the recipient operation was also refined. Choledochocholedochostomy or choledochojejunostomy to a Roux-en-Y limb became standard and significantly decreased the frequency of biliary complications. Innovations, including living donor liver transplants and deceased donor split-liver transplants, enabled more pediatric recipients to be transplanted. Improvements in portosystemic shunting and perioperative criti-cal care also were


Surgery_Schwartz

Surgery_Schwartz. liver transplants and deceased donor split-liver transplants, enabled more pediatric recipients to be transplanted. Improvements in portosystemic shunting and perioperative criti-cal care also were contributory.IndicationsIn general, any form of irreversible liver disease is an indication for a liver transplant. Chronic alcoholic disease and HCV are the most common indications in the United States. An extensive list of acute and chronic diseases of the liver that are treatable by a liver transplant is provided in Table 11-6.Offering transplants to alcoholic patients has always drawn some opposition because of the perception of it being a self-inflicted illness, as well as concerns about recidivism and the recipient’s possible inability to maintain postoperative immunosuppression and care. Yet studies have shown that such patients have excellent outcomes and that liver transplants for Table 11-6Diseases amenable to treatment by a liver transplantAutoimmune liver diseases Autoimmune


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Surgery_Schwartz. Yet studies have shown that such patients have excellent outcomes and that liver transplants for Table 11-6Diseases amenable to treatment by a liver transplantAutoimmune liver diseases Autoimmune hepatitis Primary biliary cirrhosis Primary sclerosing cholangitisCongenital Biliary atresiaViral hepatitis Hepatitis B Hepatitis CAlcoholic liver diseaseMetabolic diseases α1-Antitrypsin deficiency Cystic fibrosis Hemochromatosis Tyrosinemia Wilson’s diseaseHepatic malignancy Hepatocellular carcinoma Neuroendocrine tumor metastatic to liverFulminant hepatic failureOther Alagille syndrome Cryptogenic cirrhosis Budd-Chiari syndrome Polycystic liver disease Amyloidosisthem are cost-effective.125-127 Because patients who drink 4 to 8 ounces of liquor daily for 10 to 15 years have an increased risk of developing cirrhosis, the general requirement for accep-tance as a transplant candidate is 6 months of abstinence. Fur-thermore, most transplant centers recommend rehabilitation and Alcoholics


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Surgery_Schwartz. of developing cirrhosis, the general requirement for accep-tance as a transplant candidate is 6 months of abstinence. Fur-thermore, most transplant centers recommend rehabilitation and Alcoholics Anonymous programs.Transplants for HCV have yielded worse outcomes than transplants for other diseases.128 The reason is the universal recurrence of the virus posttransplant. Viral levels reach pre-transplant levels as early as 72 hours posttransplant.129 The course of the viral infection is often accelerated posttransplant: 10% to 20% of recipients develop cirrhosis after just 5 years.130 Studies have suggested that use of older donors may increase the chance of aggressive recurrence.131 The best method to prevent recurrence would be to eradicate the infection pretransplant, but doing so is not always possible because patients with decom-pensated cirrhosis often cannot tolerate treatment. Once recur-rence occurs, treatment methods are limited. One study found that pegylated interferon and


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Surgery_Schwartz. always possible because patients with decom-pensated cirrhosis often cannot tolerate treatment. Once recur-rence occurs, treatment methods are limited. One study found that pegylated interferon and ribavirin therapy achieved a sus-tained viral response in 44% of patients.132A substantial number of patients undergo liver transplants for cholestatic disorders. Primary biliary cirrhosis, an autoim-mune disease, is characterized by damage to the intralobular bile ducts that progresses to liver cirrhosis. Trends toward earlier treatment may explain the slight decrease in liver transplants for this disorder.133 Posttransplant outcomes in patients with this disorder have been excellent, with many centers achieving 1-year survival rates of 90% to 95%. Recurrence is relatively uncommon: a large series reported a 30% recurrence rate at 10 years posttransplant.134The second most common cholestatic disorder among liver transplant candidates is primary sclerosing cholangitis. It is characterized


Surgery_Schwartz

Surgery_Schwartz. reported a 30% recurrence rate at 10 years posttransplant.134The second most common cholestatic disorder among liver transplant candidates is primary sclerosing cholangitis. It is characterized by inflammation and fibrosis of large intraand extrahepatic biliary ducts; 70% of such patients also have inflammatory bowel disease. Recurrent cholangitis is common and increases mortality rates beyond what would be expected on the basis of laboratory values. On behalf of such patients, appeals can often be made for priority in allocation to the UNOS regional review boards. Posttransplant outcomes for such patients have been excellent. Primary sclerosing cholangitis is a significant risk factor for cholangiocarcinoma, so annual screen-ings (including imaging and measurement of serum CA 19-9 levels) should be carried out. Recurrence is fairly uncommon: studies have reported a recurrence rate of up to 20% at 10 years posttransplant.135Progressive metabolic disorders also are treatable with liver


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Surgery_Schwartz. should be carried out. Recurrence is fairly uncommon: studies have reported a recurrence rate of up to 20% at 10 years posttransplant.135Progressive metabolic disorders also are treatable with liver transplants. Hemochromatosis, an inherited disorder, results in excessive intestinal iron absorption. Iron deposition can cause cirrhosis and severe cardiomyopathy. Careful cardiac evaluation is necessary pretransplant.Another metabolic disorder, α1-antitrypsin deficiency, is characterized by insufficient levels of a protease inhibitor, resulting in early-onset emphysema and cirrhosis. Careful pul-monary evaluation is necessary pretransplant.Wilson’s disease, an autosomal recessive disorder char-acterized by impaired cellular copper transport, leads to cop-per accumulation in the liver, brain, and cornea. Patients can develop significant neurologic complications and cirrhosis. Several reports suggest improvement of neurologic deficiencies posttransplant.136,137Transplants can also be


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Surgery_Schwartz. and cornea. Patients can develop significant neurologic complications and cirrhosis. Several reports suggest improvement of neurologic deficiencies posttransplant.136,137Transplants can also be performed in patients with hepatic malignancies, but only in accordance with strict criteria. Brunicardi_Ch11_p0355-p0396.indd 38001/03/19 6:54 PM 381TRANSPLANTATIONCHAPTER 11Hepatocellular carcinoma (HCC), a complication of cirrhosis, is the most common type of hepatic malignancy. Resection is the first line of treatment if possible, but often, cirrhosis is too advanced. If the tumor meets the Milan criteria, a liver trans-plant can be performed. These criteria were established by a landmark paper in 1996 showing that patients with a single tumor under 5 cm in diameter, or with three tumors under 3 cm in diameter, in the absence of vascular invasion, had a 4-year survival rate of 85%.138 Patients with such tumors receive excep-tion points, based on their UNOS region, allowing for a timely


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Surgery_Schwartz. 3 cm in diameter, in the absence of vascular invasion, had a 4-year survival rate of 85%.138 Patients with such tumors receive excep-tion points, based on their UNOS region, allowing for a timely transplant before their tumors spread.Transplants for cholangiocarcinoma remains controver-sial but may be performed if the center has an experimental protocol in place that entails strict recipient selection. The use of a multimodality oncologic approach including neoadjuvant chemo radiotherapy with subsequent OLT achieves excellent results for patients with localized, regional lymph node-negative phCCA. Patient survival after OLT is comparable to the results of OLT for other causes.139Acute fulminant hepatic failure also is an indication for a liver transplant; in fact, such patients are the highest priority for the next available liver in their UNOS region. This devas-tating illness is defined by acute and severe liver injury with impaired synthetic function and encephalopathy in a person


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Surgery_Schwartz. priority for the next available liver in their UNOS region. This devas-tating illness is defined by acute and severe liver injury with impaired synthetic function and encephalopathy in a person who had normal liver function. It is often caused by acetaminophen overdose; acute fulminant viral hepatitis A, B, and E; other viral infections; drug toxicity; ingestion of Amanita mushrooms; acute fatty liver of pregnancy; or Wilson’s disease. A significant number of patients will recover with supportive care. The diffi-culty lies in predicting who will not recover and therefore would benefit from a liver transplant. The King’s College criteria were developed for this purpose: patients with acetaminophen-induced disease, a pH <7.3 or grade III/IV encephalopathy, a pro-thrombin time >100 seconds, and serum creatinine >3.4 mg/dL meet those criteria.140 Management of acute liver failure is very intensive. Such patients suffer from severe coagulopathy, hypoglycemia, lactic acidosis, and renal


Surgery_Schwartz

Surgery_Schwartz. and serum creatinine >3.4 mg/dL meet those criteria.140 Management of acute liver failure is very intensive. Such patients suffer from severe coagulopathy, hypoglycemia, lactic acidosis, and renal dysfunction. They are susceptible to infections, which are frequently overwhelming. Cerebral edema, a serious complication of acute liver failure, is a leading cause of death from brain herniation. Intracranial pressure monitoring and serial imaging are often necessary; if a patient develops irreversible brain damage, a transplant is not performed.Recipient SelectionThe diagnosis of cirrhosis itself is not an indication for a trans-plant. Patients may have compensated cirrhosis for years such that the traditional indication for a transplant is decompensated cirrhosis, manifested by hepatic encephalopathy, ascites, spon-taneous bacterial peritonitis, portal hypertensive bleeding, and hepatorenal syndrome (each described below).Hepatic encephalopathy is an altered neuropsychiatric state caused


Surgery_Schwartz

Surgery_Schwartz. ascites, spon-taneous bacterial peritonitis, portal hypertensive bleeding, and hepatorenal syndrome (each described below).Hepatic encephalopathy is an altered neuropsychiatric state caused by metabolic abnormalities resulting from liver failure. The early stages result in sleep disturbances and depression. As the liver disease progresses, patients can become somnolent and confused and, in the end stages, comatose. Ammonia is pro-duced by enterocytes from glutamine and from colonic bacterial catabolism, and the use of serum ammonia levels as a marker of encephalopathy is controversial because a variety of factors can influence levels. Hyperammonemia suggests worsening liver function and bypass of portal blood flow around the liver. GI bleeding and infection can exacerbate hepatic encephalopathy.Ascites (the accumulation of fluid in the abdominal cavity) that is caused by cirrhosis is a transudate with a high serum-ascites gradient (>1.1 g/dL). Associated with portal hypertension, it


Surgery_Schwartz

Surgery_Schwartz. (the accumulation of fluid in the abdominal cavity) that is caused by cirrhosis is a transudate with a high serum-ascites gradient (>1.1 g/dL). Associated with portal hypertension, it is treated initially with sodium restriction and diuretics. Refractory ascites necessitates large-volume paracentesis and eventually a transjugular intrahepatic portosystemic shunt (TIPS). Contrain-dications to TIPS placement include significant hepatic enceph-alopathy, advanced liver disease, congestive heart failure, renal insufficiency, and severe pulmonary hypertension.141Spontaneous bacterial peritonitis, an infection of the ascitic fluid without an evident intra-abdominal source, is char-acterized by fever, abdominal pain, and an ascitic fluid poly-morphonuclear count ≥250 cell/mm3 on paracentesis. The first line of empiric treatment is with a third-generation cephalospo-rin because the majority of cases are caused by aerobic gram-negative microbes such as E. coli, although Gram stain and culture


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Surgery_Schwartz. first line of empiric treatment is with a third-generation cephalospo-rin because the majority of cases are caused by aerobic gram-negative microbes such as E. coli, although Gram stain and culture results should be used to guide therapy.Portal hypertensive bleeding can be a devastating event for patients with cirrhosis. Each bleeding event carries a 30% mortality rate and accounts for a third of all deaths related to cirrhosis. Only 50% of bleeding events cease spontaneously, so treatment must be expedient. The initial medical treatment is with vasopressin and octreotide. The initial intervention is endoscopy with sclerotherapy and band ligation of bleeding varices. If those initial attempts fail, more aggressive treatment is necessary with a balloon tamponade (using a Sengstaken-Blakemore tube) and with emergent TIPS placement. The last line of treatment is emergency surgery to place a portosystemic shunt, transect the esophagus, or devascularize the gastroesoph-ageal junction


Surgery_Schwartz

Surgery_Schwartz. tube) and with emergent TIPS placement. The last line of treatment is emergency surgery to place a portosystemic shunt, transect the esophagus, or devascularize the gastroesoph-ageal junction (Sugiura procedure). Preventing variceal bleed-ing is essential and can be achieved, with some success, using β-blockers.Hepatorenal syndrome is a form of acute renal failure that develops as liver disease worsens. The etiology is unclear, but splanchnic vasodilation from portal hypertension and increased production of circulating vasodilators result in a decline in renal perfusion. Characterized by oliguria (<500 mL of urine/day) and low urine sodium levels (<10 mEq/L), hepatorenal syndrome is often reversed by a liver transplant, even after dialysis depen-dence. Pretransplant, other causes of renal failure need to be excluded, including ATN, drug nephrotoxicity, and chronic renal disease. The initial medical therapy includes octreotide, midodrine, and vasopressin analogs, but the syndrome often


Surgery_Schwartz

Surgery_Schwartz. failure need to be excluded, including ATN, drug nephrotoxicity, and chronic renal disease. The initial medical therapy includes octreotide, midodrine, and vasopressin analogs, but the syndrome often progresses to dialysis dependence.The Model for End-Stage Liver Disease (MELD) was originally developed to assess risk for TIPS placement.142 Later analysis revealed it to be an excellent model to predict survival among patients with cirrhosis, especially those on the waiting list for a liver transplant.143 In 2002, liver graft allocation was restructured to be based on the MELD score.Although the historic indication for a liver transplant is decompensated cirrhosis, a landmark analysis comparing wait-ing list mortality with posttransplant mortality established that a minimum MELD score of 18 is necessary to have a survival benefit posttransplant. A MELD score between 15 and 18 does not confer a survival advantage, but a transplant may be justified if the patient has significant morbidity


Surgery_Schwartz

Surgery_Schwartz. is necessary to have a survival benefit posttransplant. A MELD score between 15 and 18 does not confer a survival advantage, but a transplant may be justified if the patient has significant morbidity from cirrhosis.144Acute liver failure itself is an indication for a liver trans-plant. To qualify for Status 1 (first priority for a donor liver within the UNOS region), the transplant candidate must meet the following criteria: (a) onset of hepatic encephalopa-thy within 8 weeks after the first symptoms of liver disease; Brunicardi_Ch11_p0355-p0396.indd 38101/03/19 6:54 PM 382BASIC CONSIDERATIONSPART I(b) absence of preexisting liver disease; and (c) ventilator depen-dence, dialysis, or an international normalized ratio (INR) >2.0.ContraindicationsIn general terms, contraindications to a liver transplant include insufficient cardiopulmonary reserve, uncontrolled malignancy or infection, and refractory noncompliance. Older age is only a relative contraindication: carefully selected


Surgery_Schwartz

Surgery_Schwartz. a liver transplant include insufficient cardiopulmonary reserve, uncontrolled malignancy or infection, and refractory noncompliance. Older age is only a relative contraindication: carefully selected recipients over the age of 70 years can achieve satisfactory outcomes.145Patients with reduced cardiopulmonary reserve are unlikely to survive a liver transplant. Candidates should have a normal ejection fraction. If coronary arterial disease is pres-ent, they should undergo revascularization pretransplant. Severe chronic obstructive pulmonary disease (COPD) with oxygen dependence is a contraindication. Severe pulmonary hyper-tension with a mean pulmonary artery pressure greater than 35 mmHg that is refractory to medical therapy is also a contra-indication. Candidates with pulmonary hypertension should be evaluated with a right heart catheterization.For candidates with alcoholic liver disease, few reliable predictors of posttransplant relapse exist.146 Most centers require 6 months of


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Surgery_Schwartz. should be evaluated with a right heart catheterization.For candidates with alcoholic liver disease, few reliable predictors of posttransplant relapse exist.146 Most centers require 6 months of abstinence from drugs and alcohol. Insurance com-panies often make more stringent demands, including random drug screening and 1 year of abstinence.Uncontrolled infections pretransplant are a substantial risk posttransplant when the patient becomes significantly immuno-suppressed. Fungal and multidrug-resistant bacterial infections are relative contraindications. Some centers require an extended period of treatment and documented eradication pretransplant. HIV infection is a relative contraindication; some centers have strict protocols that exclude patients with a history of acquired immunodeficiency syndrome (AIDS)-related illnesses as well as those who are coinfected with HCV.Ideally, patients with a history of malignancy (with the exception of HCC) should be cured of the cancer pretransplant.


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Surgery_Schwartz. syndrome (AIDS)-related illnesses as well as those who are coinfected with HCV.Ideally, patients with a history of malignancy (with the exception of HCC) should be cured of the cancer pretransplant. In most cases, this means eradication, completion of curative therapy, and absence of recurrence over a certain period of time, which varies by the tumor type, but can be up to 5 years or lon-ger for aggressive tumors (see “Malignancies”).Surgical ProcedureA liver transplant is among the most extensive operations per-formed, and it can be associated with considerable blood loss. A bilateral subcostal incision with midline extension is used. Mechanical retraction spreads the rib cage to allow access. The ligamentous attachments of the liver are dissected free. The vascular structures are isolated, including the suprahepatic and infrahepatic vena cava, the portal vein, and hepatic artery (Fig. 11-15). The bile duct, portal structures, and vena cava are divided, completing the hepatectomy


Surgery_Schwartz

Surgery_Schwartz. including the suprahepatic and infrahepatic vena cava, the portal vein, and hepatic artery (Fig. 11-15). The bile duct, portal structures, and vena cava are divided, completing the hepatectomy (Fig. 11-16)—often the bloodiest and most difficult part of the operation, particularly in the presence of extensive varices and severe coagulopathy.After the liver is removed, the anhepatic phase begins. This phase is characterized by the absence of inferior vena caval return to the heart and by portal congestion due to clamp-ing of the portal vein. Significant hemodynamic instability and increased variceal bleeding can occur. Patients who are unable to tolerate this phase can be placed on venovenous bypass, with cannulas drawing blood from the IVC via the femoral vein and via the portal vein, returning it to the systemic circulation via the subclavian vein. Venovenous bypass itself can cause complica-tions, including air embolism, thromboembolism, and trauma to the cannulated vessels.Figure


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Surgery_Schwartz. it to the systemic circulation via the subclavian vein. Venovenous bypass itself can cause complica-tions, including air embolism, thromboembolism, and trauma to the cannulated vessels.Figure 11-15. Cirrhotic liver immobilized in preparation for com-plete hepatectomy.Figure 11-16. Isolation and division of the hilar structures to dis-eased liver-hepatic artery, portal vein, and common bile duct.The donor liver is placed in the orthotopic position. The suprahepatic vena caval anastomosis is performed first in an end-to-end fashion, followed by the infrahepatic vena caval and portal anastomosis, both also end-to-end. The liver is then reper-fused, often leading to a period of hemodynamic instability and cardiac arrhythmias due to the release of byproducts of ischemia from the donor liver. Coagulopathy also can worsen because of these byproducts as well as fibrinolysis.The arterial anastomosis between the donor common hepatic or celiac trunk is most often performed with the recipi-ent


Surgery_Schwartz

Surgery_Schwartz. Coagulopathy also can worsen because of these byproducts as well as fibrinolysis.The arterial anastomosis between the donor common hepatic or celiac trunk is most often performed with the recipi-ent CHA in an end-to-end fashion. Of course, many variations are possible. After arterial reperfusion, the bile duct anastomosis is performed between the donor and recipient common ducts, also in an end-to-end fashion. If necessary for technical reasons, the recipient common duct can be joined to a Roux-en-Y limb. Some surgeons choose to insert a T-tube or place internal stents in the common bile duct to protect the anastomosis.The piggyback technique is a common variation of the standard technique. The recipient’s IVC is preserved by care-fully dissecting off the posterior aspect of the liver. This added dissection is a disadvantage of this variation, often increas-ing hepatectomy time and blood loss. The recipient’s liver is Brunicardi_Ch11_p0355-p0396.indd 38201/03/19 6:55 PM


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Surgery_Schwartz. liver. This added dissection is a disadvantage of this variation, often increas-ing hepatectomy time and blood loss. The recipient’s liver is Brunicardi_Ch11_p0355-p0396.indd 38201/03/19 6:55 PM 383TRANSPLANTATIONCHAPTER 11removed by dividing it at the confluence of the hepatic veins. The preserved IVC is an advantage of this variation, allow-ing venous return from the lower body to the heart during the anhepatic phase and improving renal perfusion. No randomized studies, however, have demonstrated the superiority of the pig-gyback technique over the standard technique.Pediatric TransplantsOutcomes after pediatric liver transplants are among the best after any type of transplant, with a 1-year survival rate of 90%. The most common indication is biliary atresia. After diagno-sis is confirmed, a Kasai procedure is promptly carried out: a Roux-en-Y loop of bowel is directly anastomosed to the hilum of the liver. The Kasai procedure often allows time for the chil-dren to grow in size,


Surgery_Schwartz

Surgery_Schwartz. a Kasai procedure is promptly carried out: a Roux-en-Y loop of bowel is directly anastomosed to the hilum of the liver. The Kasai procedure often allows time for the chil-dren to grow in size, reducing the risk of a transplant when it is required, as it eventually is in 75% of such children.The other common indication for a pediatric liver trans-plant is a metabolic disorder, such as α1-antitrypsin deficiency, tyrosine metabolism deficiencies, and primary oxalosis. Since the MELD score was developed for adults, pediatric liver allo-cation is based on an analogous model, the Pediatric End-Stage Liver Disease (PELD) score, which incorporates bilirubin lev-els, INR, albumin levels, age, and growth failure.The surgical procedure is similar to the adult procedure. Graft implantation is more challenging, given the pediatric recipient’s smaller vascular structures. As a result, surgical complications are much more common in pediatric recipients. Hepatic artery thrombosis is about three times


Surgery_Schwartz

Surgery_Schwartz. given the pediatric recipient’s smaller vascular structures. As a result, surgical complications are much more common in pediatric recipients. Hepatic artery thrombosis is about three times more common. Donor size matching is very important in the pediatric popula-tion and often limits the donor pool for pediatric recipients. To address this issue, deceased donor split-liver transplants and liv-ing donor transplants (both described in the following sections) have been developed.Deceased Donor Split-Liver TransplantsA deceased donor allograft can be split into two grafts, most frequently into a left lateral segment for a child and an extended right segment for an adult (Fig. 11-17). It can be done in vivo (during the donor operation) or ex vivo (on the back table after the donor liver is removed). Both techniques have simi-lar outcomes. Increased morbidity is associated with splitting allografts, whether for adult or pediatric recipients; however, the technique is justified given the


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Surgery_Schwartz. removed). Both techniques have simi-lar outcomes. Increased morbidity is associated with splitting allografts, whether for adult or pediatric recipients; however, the technique is justified given the donor shortage and has been important for improving access to transplants for pediatric recipients.147Living Donor TransplantsDonation by an adult living donor to an adult recipient requires either the right or left lobe of the liver (Fig. 11-18). Donation by an adult living donor to a pediatric recipient requires the left lateral lobe (Fig. 11-19). Donor safety is paramount. The over-all donor mortality rate after donation was 0.4%, and the over-all complication rate was 40%, with multiple complications occurring in 19% of the patients. The rate of serious complica-tions resulting in lasting disability was 1.1%, with liver failure or death in 0.4%148 Careful donor selection is vital. Potential donors should be medically and psychologically healthy, their hepatic anatomy should be


Surgery_Schwartz

Surgery_Schwartz. lasting disability was 1.1%, with liver failure or death in 0.4%148 Careful donor selection is vital. Potential donors should be medically and psychologically healthy, their hepatic anatomy should be amenable to donation, and absolutely no coercion can occur. A separate donor team should serve as the donor advocate and thoroughly explain all risks.Careful recipient selection is essential. Transplant can-didates also must qualify for a deceased donor liver trans-plant because a significant number of living donor transplant DonorLeft hepatic veinLeft portal veinLeft hepatic arteryRecipientHepatic arteryPortal veinRoux limbFigure 11-17. Donor and recipient procedure for living donor liver transplant into a pediatric recipient.recipients will eventually require a retransplant. Transplant can-didates should be medically fit enough to withstand the rigors of the operation and of the postoperative course with a partial graft. An absolute contraindication is a critical illness: the limited


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Surgery_Schwartz. should be medically fit enough to withstand the rigors of the operation and of the postoperative course with a partial graft. An absolute contraindication is a critical illness: the limited suc-cess of such transplants does not justify the risks to the living donor. The obvious advantages of a living donor transplant are that it can be done expediently (avoiding the waiting list mortal-ity associated with candidates for a deceased donor transplant) and that it can be planned.Postoperative CareA liver transplant imposes significant trauma on the major organ systems. Immediately posttransplant, the first goal is to stabi-lize those systems. Acid-base equilibrium and hemodynamic stability are often difficult to maintain but are essential. Periods of hypotension can increase the risk of hepatic artery throm-bosis. Careful attention needs to be paid to ongoing bleeding. Appropriate hemoglobin levels should be maintained. Ongoing bleeding mandates a return trip to the operating room; the


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Surgery_Schwartz. artery throm-bosis. Careful attention needs to be paid to ongoing bleeding. Appropriate hemoglobin levels should be maintained. Ongoing bleeding mandates a return trip to the operating room; the rate of reoperation can be as high as 25% among high-risk patients. Transfusion of platelets and fresh frozen plaza must be done prudently because theoretically their administration can increase the risk of hepatic artery thrombosis. Graft function should be evaluated frequently; if it is impaired, an ultrasound is urgently required to assess for the presence of vascular complications.Brunicardi_Ch11_p0355-p0396.indd 38301/03/19 6:55 PM 384BASIC CONSIDERATIONSPART ICHARHVMPVMHVLHVLHVS4S2FLS3IVCIVCLHVRHVMHVLHDLHALPVMPVPHACBDR.P.V.R.P.A.RHDC.A.C.D.ABFigure 11-18. A. Hepatic transection completed for right lobe removal. CA = cystic artery; CBD = common bile duct; CD = cystic duct; FL = falciform ligament; IVC = inferior vena cava; LHD = left hepatic duct; LHV= left hepatic vein; MHV = middle


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Surgery_Schwartz. for right lobe removal. CA = cystic artery; CBD = common bile duct; CD = cystic duct; FL = falciform ligament; IVC = inferior vena cava; LHD = left hepatic duct; LHV= left hepatic vein; MHV = middle hepatic vein; MPV = main portal vein; PHA = proper hepatic artery; RHA = right hepatic artery; RHV = right hepatic vein; RPV = right portal vein; S2, S3, S4 = segments 2, 3, and 4. B. Implantation of the donor right lobe with the MHV. CHA = common hepatic artery. (Reproduced with permission from Gruessner RWG, Benedetti E: Living Donor Organ Transplantation. New York, NY: McGraw-Hill Education; 2008.)Evaluation of Graft FunctionEvaluation of the graft begins in the operating room. Its appearance overall, any swelling, and the quantity and quality of bile production after reperfusion can help assess function. In the intensive care unit, hemodynamic stability, correc-tion of coagulopathy, euglycemia, successful temperature regulation, clearance of lactic acid, and restoration of neuro-logic


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Surgery_Schwartz. function. In the intensive care unit, hemodynamic stability, correc-tion of coagulopathy, euglycemia, successful temperature regulation, clearance of lactic acid, and restoration of neuro-logic status are all signs of a functioning graft, even before the first set of liver function test results are obtained. Trans-aminases usually peak by postoperative day 2. An aspartate transaminase (AST) level greater than 2500 IU/L is sugges-tive of significant injury. Cholestasis usually peaks from Brunicardi_Ch11_p0355-p0396.indd 38401/03/19 6:55 PM 385TRANSPLANTATIONCHAPTER 11Figure 11-19. A. Hepatic transection completed for removal of left lateral segments (S2 and S3). Bile ducts to segments 2 and 3 divided; vascular structures still intact. B. Implantation of the donor left lobe. (Reproduced with permission from Gruessner RWG, Benedetti E: Living Donor Organ Transplantation. New York, NY: McGraw-Hill Education; 2008.)S2 + 3ABpostoperative day 7 to 12. The INR should improve shortly


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Surgery_Schwartz. with permission from Gruessner RWG, Benedetti E: Living Donor Organ Transplantation. New York, NY: McGraw-Hill Education; 2008.)S2 + 3ABpostoperative day 7 to 12. The INR should improve shortly after reperfusion.In 3% to 4% of patients undergoing a liver transplant, the graft does not function for any identifiable reason, a condition termed primary nonfunction; in such cases, a retransplant is the only option. Some studies suggest that a peak AST level of 5000 IU/L may be predictive of primary nonfunction.149-151 Factors associated with primary nonfunction include donor macroste-atosis, prolonged cold and warm ischemic times, and prolonged donor hospital stay.151ComplicationsVascular complications occur in about 8% to 12% of recipi-ents and include thrombosis, stenosis, and pseudoaneurysm formation.The most common vascular complication is hepatic artery thrombosis. Initial reviews suggest that its incidence is between 1.6% and 4%152; the mortality rate is 50%, even after defini-tive


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Surgery_Schwartz. formation.The most common vascular complication is hepatic artery thrombosis. Initial reviews suggest that its incidence is between 1.6% and 4%152; the mortality rate is 50%, even after defini-tive therapy.153 Early presentation can be quite dramatic, with fulminant hepatic necrosis, primary nonfunction, transamini-tis, or fever. Late presentation, however, can be asymptom-atic or subtle, with cholangitis, bile leak, mild transaminitis, hepatic abscesses, or failure to thrive. Diagnostic imaging with ultrasound has more than 90% sensitivity and specificity. If hepatic artery thrombosis is identified, urgent reexploration is needed. A thrombectomy or revision of an anastomosis may be successful, but with significant hepatic necrosis, a retransplant is necessary.Thrombosis of the portal vein is very uncommon. Signs of early thrombosis include liver dysfunction, ascites, and variceal bleeding. Upon diagnosis, an operative thrombectomy should be attempted.Biliary complications remain the


Surgery_Schwartz

Surgery_Schwartz. is very uncommon. Signs of early thrombosis include liver dysfunction, ascites, and variceal bleeding. Upon diagnosis, an operative thrombectomy should be attempted.Biliary complications remain the “Achilles’ heel” of liver transplantation, affecting 10% to 35% of these organ recipients. Signs include fever and abdominal pain, with bilious drainage from surgical drains. Diagnosis is made with cholangiography.Complications manifest themselves as leaks or strictures. Leaks require a reoperation and surgical correction, whereas strictures can most often be managed with radiologic or endo-scopic interventions. Two common reconstructions are cho-ledochostomy and choledochojejunostomy. Some centers also routinely use T-tube stents or internal stents. Consensus has not been reached as to which reconstruction technique is superior. Early infectious complications are often associated with initial graft function and pretransplant risk factors. Intra-abdominal infections should raise concerns of


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Surgery_Schwartz. technique is superior. Early infectious complications are often associated with initial graft function and pretransplant risk factors. Intra-abdominal infections should raise concerns of a possible bile leak. Fungal infections are often associated with poor graft function. Given the immunosuppressed and compromised state of liver recipi-ents, early infectious complications can be devastating.The types of opportunistic infections that occur in liver transplant recipients are similar to those that occur in other types of solid organ transplant recipients and are due to suppression of cell-mediated immunity by chronic immunosuppressive drug administration.Acute rejection occurs in approximately 20% of liver recipients. The first line of treatment is with a high dose of a corticosteroid, which is usually effective; if not, antilympho-cyte therapy is initiated. Rejection of the liver (unlike other transplanted organs) does not adversely affect patient or graft survival rates. Maintenance


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Surgery_Schwartz. is usually effective; if not, antilympho-cyte therapy is initiated. Rejection of the liver (unlike other transplanted organs) does not adversely affect patient or graft survival rates. Maintenance immunosuppression consists of a corticosteroid, tacrolimus, and mycophenolate.INTESTINE AND MULTIVISCERAL TRANSPLANTATIONAfter the introduction of long-term total parenteral nutrition (TPN) in the late 1970s and the early success of liver, kidney, and heart transplants, the first attempts at intestine transplants were made. Over the first two decades, the results were dismal. But the introduction of the immunosuppressive drug tacrolimus in the late 1980s led to significant improvement in graft and patient survival rates. Nonetheless, intestine transplants remain the least frequently performed of all transplants, with the lowest graft survival rates.The main obstacle is the high immunogenicity of the intestine, caused by its abundant lymphoid tissue. High lev-els of immunosuppression are


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Surgery_Schwartz. of all transplants, with the lowest graft survival rates.The main obstacle is the high immunogenicity of the intestine, caused by its abundant lymphoid tissue. High lev-els of immunosuppression are needed, yet the rejection rate is still high. The microbial colonization of the intestine confers the risk of translocation of pathogenic microorganisms into the recipient’s circulation, causing severe systemic infections. Through the first decade of the 21st century, the survival of patients on long-term TPN was superior to the survival of intes-tine transplant recipients, so a transplant was considered only as rescue therapy for patients with life-threatening TPN-related complications.Brunicardi_Ch11_p0355-p0396.indd 38501/03/19 6:55 PM 386BASIC CONSIDERATIONSPART IOver the last several years, improvements in surgical tech-niques, in perioperative and postoperative care, and particularly in immunosuppressive protocols have led to significantly bet-ter patient and graft survival rates


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Surgery_Schwartz. improvements in surgical tech-niques, in perioperative and postoperative care, and particularly in immunosuppressive protocols have led to significantly bet-ter patient and graft survival rates posttransplant.154 Recent data indicate that survival rates after an intestine transplant often are better than, or at least similar to, survival rates among patients receiving chronic TPN in the home setting with improved qual-ity of life in selected patients.155 Today, an intestine or multivis-ceral transplant is recognized as a feasible treatment.Indications and Recipient SelectionAn intestine transplant is indicated for patients with irreversible intestine failure in combination with TPN failure. The defini-tion of intestine failure does not specify the exact length of the remaining intestine. Intestine failure is typically multifactorial. Variables include what part of the small intestine is absent, whether or not the ileocecal valve is present, whether or not the patient underwent an


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Surgery_Schwartz. Intestine failure is typically multifactorial. Variables include what part of the small intestine is absent, whether or not the ileocecal valve is present, whether or not the patient underwent an ostomy, and how long the remaining colon is. TPN failure is defined as significant biochemical or pathologic evidence of liver injury, loss of central vein access with thrombosis of at least two central veins, frequent indwell-ing catheter infection or a single episode of fungal infection, and recurrent episodes of severe dehydration despite IV fluid supplementation.Indications for a transplant differ between the adult and pediatric population. The leading causes of intestine failure are summarized in Table 11-7. The disease involvement of organs other than the intestine dictates the extent of the operation required. Liver failure is often seen in patients on long-term TPN. If pathologic or biochemical evidence of severe liver damage is combined with signs of portal hypertension, then a


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Surgery_Schwartz. of the operation required. Liver failure is often seen in patients on long-term TPN. If pathologic or biochemical evidence of severe liver damage is combined with signs of portal hypertension, then a combined liver-intestine transplant is the treatment of choice. However, a multivisceral transplant (liver, pancreas, stomach, duodenum, and/or small intestine) might be necessary among children who suffer diffuse intestinal dysmotility syndromes and adults who develop diffuse portomesenteric thrombosis, extensive intra-abdominal desmoid disease encasing the main visceral vascular structures with concurrent short gut syndrome, or massive abdominal trauma.Table 11-7Leading causes of intestine failureCHILDRENADULTSGastroschisisVisceral ischemia secondary to SMA/SMV thrombosisMidgut volvulusCrohn’s diseaseIntestinal atresiaTraumaNecrotizing enterocolitisMesenteric desmoid tumorsMicrovillus involution diseaseRadiation enteritisHirschsprung’s diseaseMassive resection secondary to tumorsCrohn’s


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Surgery_Schwartz. diseaseIntestinal atresiaTraumaNecrotizing enterocolitisMesenteric desmoid tumorsMicrovillus involution diseaseRadiation enteritisHirschsprung’s diseaseMassive resection secondary to tumorsCrohn’s diseaseChronic intestinal pseudo-obstructionPseudo-obstructionAutoimmune enteropathySMA = superior mesenteric artery; SMV = superior mesenteric veinSurgical ProcedureFor both the donor and recipient surgery, the key decision is which organs will be transplanted.156 For an isolated intestine transplant, the blood supply is based on the arterial inflow from the SMA and on the venous outflow from the superior mesen-teric vein (SMV). Both vessels are isolated at the root of the mesentery.For a combined liver-intestine transplant, the blood supply is based on the arterial inflow from the celiac axis and SMA, which are procured en bloc with an aortic patch. The liver, duo-denum, pancreas, and small intestine—because of their close anatomic relationship—are procured en bloc. If the hepatoduo-denal


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Surgery_Schwartz. and SMA, which are procured en bloc with an aortic patch. The liver, duo-denum, pancreas, and small intestine—because of their close anatomic relationship—are procured en bloc. If the hepatoduo-denal ligament is left intact, no biliary reconstruction is neces-sary, which virtually eliminates the risk of postoperative biliary complications.157 Because the entire splanchnic system drains into the liver, venous drainage is achieved by anastomosis of the hepatic veins to the recipient’s vena cava.For both an isolated intestine transplant and a combined liver-intestine transplant, the proximal transection of the GI tract occurs at the first portion of the duodenum. For a multivisceral transplant, the stomach is part of the graft; hence, the transection of the GI tract occurs at the distal esophagus. Figures 11-20 to 11-22 show these three main types of transplants.The vast majority of intestine transplants use a deceased donor organ. However, advances in surgical techniques have made the


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Surgery_Schwartz. Figures 11-20 to 11-22 show these three main types of transplants.The vast majority of intestine transplants use a deceased donor organ. However, advances in surgical techniques have made the use of living donors a feasible alternative for either an isolated intestine transplant or a combined liver-intestine transplant. With a living donor, the donor operation is slightly different: for an isolated intestine transplant, 150 to 200 cm of the donor’s ileum, on a vascular pedicle comprising the ileocolic artery and vein, are used158 (Fig. 11-23); for a combined liver-intestine transplant, performed almost exclusively for pediatric recipients, segments II and III of the donor’s liver are used, in addition to the intestine (Fig. 11-24).Figure 11-20. Isolated intestine transplant.Brunicardi_Ch11_p0355-p0396.indd 38601/03/19 6:55 PM 387TRANSPLANTATIONCHAPTER 11Figure 11-21. Combined liver-intestine transplant.Figure 11-22. Multivisceral transplant.ABFigure 11-23. A. Donor operation.


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Surgery_Schwartz. 38601/03/19 6:55 PM 387TRANSPLANTATIONCHAPTER 11Figure 11-21. Combined liver-intestine transplant.Figure 11-22. Multivisceral transplant.ABFigure 11-23. A. Donor operation. About 180 to 200 cm of distal ileum on a vascular pedicle comprising the ileocolic artery and vein are removed. B. Recipient operation. The donor’s ileocolic artery and vein (or the terminal branches of the donor’s superior mesenteric artery and vein) are anastomosed end-to-side to the recipient’s infrarenal aorta and vena cava. (Reproduced with permission from Gruessner RWG, Benedetti E: Living Donor Organ Transplantation. New York, NY: McGraw-Hill Education; 2008.)Brunicardi_Ch11_p0355-p0396.indd 38701/03/19 6:55 PM 388BASIC CONSIDERATIONSPART IFigure 11-24. Recipient operation. For a combined living donor liver-intestine transplant in a pediatric recipient, liver segments 2 and 3 are implanted in standard fashion (the donor’s left hepatic vein to the recipient’s vena cava, the donor’s left hepatic artery


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Surgery_Schwartz. transplant in a pediatric recipient, liver segments 2 and 3 are implanted in standard fashion (the donor’s left hepatic vein to the recipient’s vena cava, the donor’s left hepatic artery to the recipient’s proper or common hepatic artery, the donor’s left portal vein branch to the recipient’s portal vein trunk). The donor’s ileocolic artery and vein are anastomosed to the recipient’s infra-renal aorta and cava. In the recipient, a duodenum-to-donor ileum anastomosis and a distal Bishop-Coop ileostomy are constructed to reestablish bowel continuity. A very short Roux-en-Y loop (10 to 20 cm) is anastomosed to the donor’s bile duct(s). (Reproduced with permission from Gruessner RWG, Benedetti E: Living Donor Organ Transplantation. New York, NY: McGraw-Hill Education; 2008.)Similarly, the recipient operation also varies by the organs transplanted. Generally, the recipient’s infrarenal aorta is used to achieve the arterial inflow to the graft. For an isolated intestine transplant, venous


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Surgery_Schwartz. operation also varies by the organs transplanted. Generally, the recipient’s infrarenal aorta is used to achieve the arterial inflow to the graft. For an isolated intestine transplant, venous drainage is achieved via systemic or portomesenteric drainage; for a combined liver-intestine trans-plant or a multivisceral transplant, venous drainage is achieved via the hepatic veins. Systemic venous drainage, given its lesser technical difficulty, is preferred over portomesenteric drainage. The diversion of splanchnic flow into the systemic venous cir-culation can cause several metabolic abnormalities, but no hard evidence shows any negative impact clinically on the recipient.After the organs are perfused, the continuity of the recipi-ent’s GI tract is restored, which includes the placement of a gastrostomy or jejunostomy feeding tube and an ileostomy. In the early postoperative period, the ileostomy enables regular endoscopic surveillance and biopsy of the intestinal mucosa. Once the


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Surgery_Schwartz. of a gastrostomy or jejunostomy feeding tube and an ileostomy. In the early postoperative period, the ileostomy enables regular endoscopic surveillance and biopsy of the intestinal mucosa. Once the recipient recovers, the ileostomy can be taken down.The last, but often the most difficult, part of the recipi-ent operation is abdominal wall closure. It is especially challenging in intestine transplant recipients because they have usually undergone multiple previous procedures, resulting in many scars, ostomies, feeding tubes, and the loss of abdomi-nal domain. To provide sufficient coverage of the transplanted organs, the use of prosthetic mesh often is necessary.Postoperative CareInitial postoperative care for intestine transplant recipients does not significantly differ from that for other organ transplant recipients. In the intensive care unit, each recipient’s cardio-vascular, pulmonary, and renal function is closely monitored; aggressive resuscitation with fluid, electrolytes, and


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Surgery_Schwartz. organ transplant recipients. In the intensive care unit, each recipient’s cardio-vascular, pulmonary, and renal function is closely monitored; aggressive resuscitation with fluid, electrolytes, and blood prod-ucts is performed. Broad-spectrum antibiotics are an integral component of care.Of all solid organ transplants, intestine transplants have the highest rate of rejection. With intestine transplants, no sero-logic marker of rejection is available, so frequent biopsies and histologic evaluation of the intestinal mucosa are of utmost importance. Rejection leads to structural damage of the intes-tinal mucosa. Translocation of endoluminal pathogens into the circulation can cause systemic infections.Thanks to the introduction of new immunosuppressive protocols, the rejection rates and the overall patient and graft survival rates have improved significantly. Variations between the protocols exist, but the general concept is to induce immu-nosuppression with polyclonal T-cell antibody and


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Surgery_Schwartz. patient and graft survival rates have improved significantly. Variations between the protocols exist, but the general concept is to induce immu-nosuppression with polyclonal T-cell antibody and high doses of a corticosteroid, followed by maintenance doses of cortico-steroids and the calcineurin inhibitor tacrolimus.Immediately, posttransplant, recipients are maintained on TPN. Enteral nutrition is initiated as early as possible, but it is advanced very cautiously. It can take several weeks for the transplanted intestine to achieve structural integrity and func-tionality and for the recipient to tolerate the full strength of tube feeds.Despite all the recent advances, the complication rate posttransplant remains high. The most common complica-tions include intra-abdominal abscesses, enteric leaks, intra-abdominal sepsis, the need for a reoperation, graft thrombosis, life-threatening bleeding, and central line problems. Immuno-suppression-specific complications include rejection, PTLD,


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Surgery_Schwartz. leaks, intra-abdominal sepsis, the need for a reoperation, graft thrombosis, life-threatening bleeding, and central line problems. Immuno-suppression-specific complications include rejection, PTLD, graft-versus-host disease (GVHD), infections, and malignan-cies. Tailoring the recipient’s immunosuppression plays a critical role in preventing these complications: a low level of immunosuppression leads to graft rejection, but too much con-fers a high risk of infectious complications, PTLD, and, less commonly, GVHD—all of which are associated with a signifi-cantly increased risk of graft failure and mortality.The long-term results of intestine transplants have improved significantly, even though they still remain inferior to the results of other abdominal organ transplants.159,160HEART AND LUNG TRANSPLANTATIONHistoryThe first successful heterotopic heart transplant, in an animal model, was performed by Carrel and Guthrie in 1905.161 Subse-quent progress with cardiopulmonary bypass and


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Surgery_Schwartz. LUNG TRANSPLANTATIONHistoryThe first successful heterotopic heart transplant, in an animal model, was performed by Carrel and Guthrie in 1905.161 Subse-quent progress with cardiopulmonary bypass and immunologic modulation facilitated the first successful adult human heart transplant, performed by Christiaan Barnard in 1967 in Cape Town, South Africa.162 However, it was Norman Shumway at Stanford who persisted with heart transplants, in the face of disappointing patient outcomes at a number of early centers. Brunicardi_Ch11_p0355-p0396.indd 38801/03/19 6:55 PM 389TRANSPLANTATIONCHAPTER 11Thanks to the diligence of Shumway and colleagues in perfect-ing heart transplant techniques, along with the development, by Caves, of endomyocardial biopsy as a method of allograft rejection surveillance, human heart transplants began to reap-pear in the 1980s as a viable solution to end-stage heart failure. By 1981, the introduction of cyclosporin A finally created the necessary clinical