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Liver Transplantation for Variceal Hemorrhage
Management of Variceal Hemorrhage
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Liver Transplantation for Variceal Hemorrhage
R. Patrick Wood, MD, FACS, * Byers W. Shaw, Jr, MD, FACS, t and Layton F. Rikkers, MD*
Theoretically, liver transplantation is the ideal therapy for all patients with chronic liver disease complicated by portal hypertension and variceal hemorrhage. Only by replacing the diseased liver and reestablishing the low-resistance portal outflow through the liver are portal hemodynamics restored to normal. 30 In addition, liver transplantation is the only therapy for bleeding esophageal varices that addresses the underlying liver disease and restores the patient's hepatic functional reserve to normal. Mter successful transplantation, the patient is not only protected from recurrent variceal hemorrhage but also from the complications of encephalopathy and liver failure, which are frequently associated with other therapies for variceal hemorrhage. 36, 38, 40. 52 The use of liver transplantation as a therapy for all patients with chronic liver disease and variceal hemorrhage is, however, limited by a number of factors, including the necessity of a donor liver to perform the procedure, the mortality and morbidity associated with the procedure, the cost of both the procedure and the immunosuppressive medications, and the limited data on the long-term results of liver transplantation. • Important questions regarding the role of liver transplantation in patients with variceal hemorrhage include the following: (1) Which patients with variceal hemorrhage are candidates for liver transplantation? (2) If the transplant is to be delayed, what is the optimal therapy to prevent recurrent variceal hemorrhage and to maintain the option of subsequent transplantation? (3) In a patient who is presently a transplant candidate, how should acute variceal hemorrhage be managed? (4) In transplanting a patient with From the Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska
*Associate Professor· tProfessor :j:Professor and Chairman
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a portosystemic shunt, how does the presence of the shunt influence the transplant operation?
WHICH VARICEAL BLEEDERS ARE CANDIDATES FOR TRANSPLANTATION? It should be emphasized that liver transplantation is not a therapy for variceal hemorrhage but rather a treatment for patients with advanced liver disease. There are a number of diseases that result in portal hypertension and esophageal varices for which liver transplantation is inappropriate (Table 1). In fact, in diseases such as schistosomiasis (probably the most common cause of portal hypertension throughout the world) and portal vein thrombosis, both of which are associated with normal functional hepatic reserve, long-term prevention of variceal hemorrhage by sclerotherapy or a non transplant operation can result in a normal quality and duration of survival. 40 For the remaining patients with chronic liver disease and variceal hemorrhage, however, liver transplantation should be considered among the options for prevention and control of recurrent bleeding. Liver transplantation is indicated for the treatment of selected patients with end-stage liver disease that is medically and surgically intractable. Because there are other means available to treat patients who experience variceal hemorrhage as a complication of their liver disease, the indication for transplantation in this group of patients must be based on a complete assessment of the probability of both short-term and long-term survival and rehabilitation provided by each therapy. The survival rates for the various treatments available to control variceal hemorrhage are dependent on two factors; the etiology of the patient's liver disease and the level of liver dysfunction at the time the therapy is instituted. 6, 12, 19. 41, 42, 45 Patients with alcoholic liver disease, as a group, do worse with most interventions to control variceal hemorrhage when compared with patients with nonalcoholic liver disease. 23, 36, 40 Table 1. Diseases Associated with Portal Hypertension Not Usually Requiring Transplantation Extrahepatic, Presinusoidal 1. Portal vein thrombosis 2. Cavernomatous transformation of the portal vein 3. Splenic vein thrombosis Intrahepatic Presinusoidal 1. Schistosomiasis 2. Sarcoidosis* 3. Congenital hepatic fibrosis* 4. Arsenic toxicity 5. Myeloproliferative diseases Increased Portal Flow 1. Hepatic artery-portal vein fistula 2. Increased splenic flow (idiopathic portal hypertension) *May require transplantation as disease progresses.
r
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A large number of controlled and uncontrolled studies have reported the short-term and long-term results of shunt surgery21, 24, 31, 34, 35, 39, 56, 58 and chronic sclerotherapy. 8, 12, 27, 29, 33, 39, 47, 53-55, 59-60 The survival rates for patients undergoing chronic sclerotherapy range from 50 to 90% at 1 year and 40 to 80% at 5 years, as compared to 70 to 90% at 1 year and 40 to 60% at 5 years for patients undergoing portosystemic shunts. Although almost 90% of all liver transplants have been performed in the last 5 years, there is an extensive literature (with limited follow-up) on the results of liver transplantation. 10, 14, 15, 22, 24, 25, 43, 44, 46, 61 In a recent review of their experience with liver transplantation in patients with variceal hemorrhage, Iwatsuki et aP3 compared their results with liver transplantation in 302 patients to those reported in the literature for other therapies for variceal hemorrhage. The survival rate in the transplanted patients was 79% at 1 year and 71% at 5 years. The difference in survival rates was of greatest magnitude when Child's class C patients who received liver transplants (79% I-year and 71% 5-year survival rates) were compared with Child's C patients who were treated with portosystemic shunts (30 to 70% I-year and 13 to 35% 5-year survival rates). To put this study in perspective, however, it should be emphasized that Iwatsuki's patient population included both children and adults who had almost exclusively nonalcoholic liver diseases. In contrast, the comparison groups were derived from various series of shunted patients made up primarily of adult alcoholic cirrhotics. In addition, only 3% of the transplant patients were actively bleeding from varices at the time of the operation, whereas the patients in the comparison groups were specifically being treated for variceal hemorrhage, many of them in the emergency setting. Although the transplant and non transplant groups are not comparable in this investigation, the following conclusion is valid: in those patients with end-stage liver disease (Child's class C) who are appropriate candidates, liver transplantation provides survival results superior to any other therapy for the control of variceal hemorrhage. In patients with well-compensated liver disease (Child's class A and B patients) who experience a variceal hemorrhage, no such clear-cut recommendatiQl1 can be made. This group of patients will do well initially with any of the available therapies to control the variceal hemorrhage. In one series, the survival rate for Child's class A and B patients treated with sclerotherapy was over 95% at 1 year and over 80% at 5 years. 30 Selective or nonselective shunts in this group of patients yield survival rates of 70 to 90% at 1 year and 50 to 65% at 5 years. 19, 30, 31, 58 By comparison, data from our own center on adult liver transplant patients showed actuarial survival rates following transplantation of Child's class A and B patients of 89% at 1 year and 4 years. Figure 1 compares the survival curves for 168 adult Child's class A, B, and C patients receiving liver transplants at our institution with 348 patients in the Emory University series receiving a selective shunt. 59 The most striking characteristic is that the slope of the survival curves in the transplanted patients is flat after the first year. This indicates that the major mortality associated with transplantation is concentrated in the first year, after which the patients are unlikely to develop fatal complications. In the
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Figure 1. Survival curves for 168 adult Child's class AlB and C patients receiving liver transplants at the University of Nebraska Medical Center compared with 348 adult Child's AI Band C patients receiving selective shunts at Emory University. The actuarial survival curves for the transplanted patients were calculated by the life-table method, whereas the survival curves for the shunted patients were estimated from life-table data presented in Warren et al. 59
shunted patients, the survival curves demonstrate the continued decline in survival over time due to the progressive nature of most patients' liver disease. In addition to comparing survival rates, the therapies for controlling variceal hemorrhage must also be compared for the quality of survival that is provided. Chronic sclerotherapy is associated with a 30 to 60% incidence of rebleeding and a 15 to 30% ultimate failure rate. 19. 28, 36, 38, 40, 52 Nonselective shunts virtually eliminate rebleeding as a complication but are associated with a 40% incidence of severe recurrent encephalopathy. 28,36,38,40 Selective shunts have a lower incidence of encephalopathy (in several studies), a slightly higher incidence of rebleeding compared to nonselective shunts, and a lO% incidence of portal vein thrombosis. 37 In liver transplant patients, the rehabilitation rates following successful transplantation range from 75 to 85%.5, 9, 13, 43, 44, 57
CONTRAINDICATIONS TO LIVER TRANSPLANTATION As results have improved, the indications for transplantation have been liberalized and the contraindications have become fewer. A list of the generally accepted contraindications to transplantation is shown in Table 2. It should be emphasized that this table serves only as a general guideline and that each patient should be evaluated on an individual basis,
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Table 2. Contraindications to Liver Transplantation Absolute Contraindications Extrahepatic malignancy Active sepsis not confined to the liver or biliary system Thrombosis of the entire portal venous system Presence of potentially fatal organ system failure not expected to improve following transplantation Active alcohol or drug abuse Acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) Confirmed and repetitive history of noncompliance Relative Contraindications Extremes of age Positive AIDS serology in an asymptomatic patient Questionable history of noncompliance Multiple prior transplants
Malignancy that is not confined to the liver and overt systemic sepsis are two absolute contraindications to transplantation. In addition, complete thrombosis of the entire portal venous system (portal vein, splenic vein, and superior mesenteric vein) makes transplantation technically impossible. Because the goal of transplantation is to restore the patient to an acceptable quality of life, the presence of other life-threatening conditions that would not be expected to improve following transplantation (such as severe coronary artery disease or pulmonary disease) is also an absolute contraindication to transplantation. Active alcohol or drug abuse, the acquired immune defiCiency syndrome (AIDS), and the AIDS-related complex have also been considered absolute contraindications. Finally, a history of noncompliance with medication schedules and follow-up medical care may eliminate the patient from consideration as a candidate for transplantation. Alcoholic cirrhosis is the most frequent cause of end-stage liver disease in this country.40 In the past, active alcohol abuse was considered a contraindication to transplantation. However, a limited number of patients with alcoholic liver disease who have been abstinent for varying periods have undergone transplantation with results comparable to those obtained in most varieties of nonalcoholic liver disease. 23 Recently, Starzl et al49 have challenged the concept of not considering active alcoholics for liver transplantation. They have shown no difference in survival of active alcoholics compared to patients transplanted for nonalcoholic liver diseases. If transplantation does become the accepted form of therapy for patients with acute alcoholic hepatitis and chronic alcohol-induced liver disease, this will greatly expand the pool of potential recipients for the already scarce resource of liver donors.
EMERGENCY MANAGEMENT OF VARICEAL HEMORRHAGE Endoscopic sclerotherapy will control 80 to 90% of patients with acute variceal bleeding, with failure defined as persistent hemorrhage after two injection sessions. Terblanche54 has shown that mortality among the 10 to 20% of patients in whom sclerotherapy fails is excessive unless surgical
intervention is undertaken. The surgical procedures to choose from include portosystemic shunt, gastric devascularization, and liver transplantation. 1 If the patient is already on a waiting list as a transplant candidate, he or she should be transferred to the transplant center if possible. This will allow the greatest number of options for the patient, including emergency transplantation should a donor liver become available. Emergency transplantation will provide definitive control of bleeding varices but is limited by the availability of donor organs on an emergency basis. If a donor organ is not immediately available and surgical intervention is indicated, the procedure chosen should be one with which the surgeon has familiarity and that does not compromise subsequent transplantation. The simplest operation is esophageal transection with an end-to-end stapling device. 20, 32, 48 Other gastric devascularization procedures can be used if the surgeon has experience with such techniques. 16, 26, 50, 51 However, portal decompression more reliably controls variceal hemorrhage and has the advantage of preventing further bleeding episodes. Shunts that avoid the porta hepatis and that can be ~ompleted expeditiously are preferred. In this setting, large-bore interposition mesocaval or mesorenal shunts are advisable. If a portacaval shunt is chosen, an end-to-side portacaval anastomosis is preferable to a side-to-side shunt because the former is generally easier to perform and does not risk compromising the length of extrahepatic portal vein available for subsequent transplantation. If done carefully, portacaval shunt does not prohibit subsequent transplantation. In some ways, the dissection necessary to perform the shunt lessens the difficulty of subsequent transplantation. In treating a patient who is a recognized transplant candidate, there is little need to consider selective shunting because the apparent advantages over nonselective shunts are only realized in the long term. Short-term disadvantages of selective shunts include an increased risk of portal vein thrombosis, incomplete portal decompression, prolonged operating time, and exacerbation of ascites. 37 The more difficult issue concerns the management of the patient whose candidacy for transplantation must be assessed for the first time in the setting of acute variceal hemorrhage. As we have indicated, the choice of surgical procedure is influenced by whether or not the patient will eventually undergo transplantation. Patients who are questionable candidates for transplantation should not undergo this operation in an emergency situation. In addition to those patients with one or more of the contraindications listed earlier, exceptions to emergency transplantation include active alcoholics whose rehabilitation potential has not been assessed, patients in whom the cause of portal hypertension remains unknown, and Child's class A patients who are not yet clearly in need of transplantation. These patients should be treated with one of the nontransplant procedures, and the choice should be made with the assumption that the patient will be a subsequent transplant recipient. The patient can be stabilized and evaluated as a transplant candidate more carefully at a later date.
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VARICEAL HEMORRHAGE IN THE PATIENT WITH GOOD HEPATIC FUNCTIONAL RESERVE An unanswered question is what therapy is most appropriate for that select group of patients who experience a variceal hemorrhage but have minimal or no evidence of liver dysfunction and whose bleeding can initially be controlled medically. Because the incidence of rebleeding following an initial episode of variceal hemorrhage is at least 70%, some therapeutic intervention to prevent recurrent hemorrhage seems warranted. Randomized trials of sclerotherapy versus shunt surgery suggest that endoscopic variceal sclerosis is an appropriate initial therapy in this group of patients with either shunt surgery or transplantation reserved for sclerotherapy failures. 39, 58 Some patients, however, are not candidates for initial management with sclerotherapy. These include the following: (1) patients who bleed from gastric varices, (2) patients with bleeding from portal hypertensive gastropathy, (3) noncompliant patients, and (4) individuals who live in remote areas where a rebleeding episode may be fatal owing to limited access to medical facilities. 39 Patients who are not candidates for initial management with sclerotherapy and those patients who fail sclerotherapy should be considered candidates for either shunt surgery or transplantation. In selecting a patient for either a distal splenorenal shunt (DSRS) or transplantation, the group at Emory3° uses a variety of tests, including liver volume and galactose elimination capacity, to identify those patients whose hepatic reserve is sufficiently limited to warrant proceeding with transplantation. Shunts are reserved for good-risk patients. These investigators believe that their data ". . . show that selective shunt is the surgical procedure of choice in Child's AlB cirrhotics who fail sclerotherapy because it is safer (lower operative mortality), less expensive, and carries no risk of chronic immunosuppression." However, their data do not support this broad generalization. As shown in Figure 1, the early mortality associated with the transplantation of Child's A and B patients is higher than with selective shunts, but this difference is no longer apparent at 18 months. Beyond 18 months, the survival curve remains flat for the transplanted patients but continues to progressively decline in the shunted patients. Although the cost of a liver transplant is substantially greater than that of a DSRS, the successfully transplanted patient has an excellent prognosis both for survival and for a normal quality of life. In contrast, the majority of patients receiving a shunt will experience progressive deterioration of hepatic function and will eventually require a liver transplant for long-term survival. Although transplanted patients are at risk for complications related to the prolonged use of immunosuppression, these complications become less likely over time as the dosages of immunosuppressive medication are reduced to maintenance levels. This is in contrast to the complications of progressive liver disease faced by patients who receive a shunt. There is no single test or series of tests that provide definitive criteria to identifY those patients who will be best treated with a shunt versus those who should undergo a transplant. Rather, the decision to shunt or transplant must be made on a case-by-case basis. In our institution, patients with
variceal hemorrhage but well-compensated liver disease undergo a complete evaluation by the transplant team, the shunt surgeon, and our adult gastroenterology group. If a shunt is selected, the transplant team is kept informed of the patient's postoperative course and consulted if the patient's hepatic function deteriorates at any point following the shunt. Patients who manifest signs or symptoms of progression of their liver disease are reevaluated by the transplant service and, if indicated, are activated as candidates for transplantation. If a decision is made to proceed with a shunt, we prefer the DSRS if anatomy allows and the patient does not have medically intractable ascites. This shunt effectively controls bleeding and has an excellent long-term patency rate. In addition, four of seven controlled studies have reported a lower incidence of encephalopathy following DSRS than after nonselective shunts. 37 An additional advantage of the DSRS is that the hepatic hilum is not dissected and the presence of a DSRS does not adversely affect the performance of a subsequent liver transplant. Patients who undergo a successful shunt operation should be monitored at 6-month intervals to identify any signs of progressive liver dysfunction. The successful control of variceal hemorrhage does not eliminate the need for close follow-up in potential transplant candidates who receive a DSRS. The goal should be to refer patients for transplantation while they remain a low risk and have the greatest chance of a successful result.
LIVER TRANSPLANTATION IN THE PATIENT WITH A PORTOSYSTEMIC SHUNT Over the past 49 months, we have transplanted 203 adult patients, 11 of whom have had prior portosystemic shunts. Six patients had nonselective shunts (two end-to-side portacaval, two mesorenal, two mesocaval, and one central splenorenal), and five individuals had selective shunts (all DSRS). The shunts had been performed from 1 month to 26 years prior to the transplant. Nine of the 11 (81%) patients survived and were discharged from the hospital. Iwatsuki et a}23 also failed to show Significant differences in outcome between previously shunted and unshunted patients after hepatic transplantation. In individual cases, however, prior portosystemic shunts (especially the portacaval variety) can compromise the transplant operation. In the discussion that follows, we present our approach to the preoperative evaluation of patients with prior portosystemic shunts and the intraoperative management of these patients during the transplant procedure. Preoperative Assessment Patients with a prior portosystemic shunt should have the patency of their shunt determined with duplex ultrasonography. If ultrasonography demonstrates patency in a patient with a nonselective shunt, no further evaluation of the shunt is required. However, some transplant centers recommend both selective mesenteric angiography and venography of the inferior vena cava to evaluate a nonselective shunt. 2 , 7 Initially, we used duplex ultrasonography to assess the patency of a DSRS, and we removed
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the spleen in all patients with a patent DSRS. However, one of our patients with a DSRS developed portal vein thrombosis in the immediate posttransplant period secondary to extensive collateralization into the splenic vein remnant. We now obtain mesenteric angiograms on all patients with a patent DSRS. When extensive collateralization to the shunt is present, we believe that a splenectomy alone may be inadequate to "disconnect" the shunt. Intraoperative Management Whether a portacaval shunt was performed in an end-to-side or sideto-side fashion, the operative approach at the time of transplantation is the same: the infrahepatic inferior vena cava (IVe) and portal vein proximal and distal to the shunt must be controlled. If there is an adequate length of the Ive between the shunt and the liver to allow the placement of a vascular clamp, the shunt is left intact, the native liver is removed, and the suprahepatic and infrahepatic caval anastomoses are performed. As the shunt provides portal decompression, the portal vein limb of the venous bypass system is not required during the anhepatic phase of the transplant. After the infrahepatic IVe anastomosis has been completed, a vascular clamp is placed on the lve across the shunt and a second clamp is placed on the proximal portal vein. The shunt is then transected, leaving a cuff of portal vein on the lve. The anastomotic site in the IVe is oversewn, and the portal vein anastomosis is completed in the usual end-to-end fashion. If there is insufficient length of infrahepatic lve bet~een the shunt and the liver to place a vascular clamp safely, the transplant surgeon has two options. The first option is to proceed as previously described and, after completion of the suprahepatic IVe anastomosis, dismantle the shunt. In this case, the portal vein limb of the venous bypass would not be used and there would be no decompression of the portal venous system during the infrahepatic lve and portal vein anastomoses. The second option is to dismantle the shunt before the native liver is removed and to place the portal vein cannula of the venous bypass as is done routinely for all adult transplants. This option requires that the portal vein be of sufficient length and caliber to accommodate the portal vein cannula. A patent mesorenal or mesocaval shunt need not be disturbed during the initial dissection of the native liver. In addition, because the shunt decompresses the portal venous system, there is no need for the portal vein limb of the venous bypass system during the anhepatic phase of the transplant operation. Because this is a total shunt, it must be isolated and ligated prior to the completion of the transplant procedure. Unlike a mesocaval or mesorenal shunt, a patent central splenorenal shunt requires that the splenic vein be identified and isolated at the level of its junction with the portal vein before the patient is placed on venous bypass and the native liver is removed. The presence of the shunt, however, does not increase the technical difficulty of the initial dissection of the recipient's liver, although the isolation of the splenic vein may be tedious. There is no need for the portal vein limb of the venous bypass during the anhepatic phase, because this shunt provides adequate portal decompres-
sion. However, it is important that the shunt be ligated after the portal vein anastomosis is completed. This is usually accomplished by doubly ligating the previously isolated splenic vein just before its junction with the portal vein. The presence of a DSRS does not increase the difficulty of the transplant procedure because the hepatic hilum is not disturbed during the performance of the shunt. This shunt, in theory, does not provide decompression for the mesenteric side of the portal circulation, and the portal vein limb of the venous bypass must be inserted to decompress the portal venous system during the anhepatic phase. There are differing opinions regarding the management of a DSRS once the new liver has been implanted. Brems et aF recommend that the shunt not be disturbed. They have had no complications with this approach in two patients. The Pittsburgh group7 recommends both a splenectomy and ligation of the shunt at the level of the renal vein. They were able to perform a splenectomy in all four of their patients transplanted with a patent DSRS; in three of the four, the shunt was also ligated. However, one of these individuals developed pancreatitis and a pancreatic fistula secondary to dissection of the shunt. In all five of our patients transplanted with a patent DSRS, splenectomy was performed and no attempt was made to ligate the shunt. One patient, described previously, developed a portal vein thrombosis due to extensive collaterals into the splenic vein remnant. In addition to the mesenteric angiogram obtained preoperatively, after the donor liver has been implanted, a contrast study of the portal venous system is obtained by cannulating a vein in the mesentery of the proximal jejunum. If the portal vein is well visualized (indicating preferential flow of the contrast toward the liver), the shunt may be left undisturbed. If there is nonvisualization of the portal vein, then a splenectomy is performed and an attempt is made to ligate the collaterals between the mesenteric portal system and the remnant of the shunt.
SUMMARY At the present time, liver transplantation must be considered among the treatment options for patients with variceal hemorrhage. For a significant percentage of variceal bleeders throughout the world, however, transplantation is not a viable option either because the patient is not an appropriate transplant candidate or because of the etiology of the patient's portal hypertension. Sclerotherapy and portosystemic shunts remain the mainstay of therapy for these patients. The survival rates with liver transplantation are superior to those reported for other therapies for variceal hemorrhage in patients who have moderate or severe liver disease in addition to variceal hemorrhage. Child's C patients whose variceal hemorrhage is controlled medically should be evaluated for transplantation and receive chronic sclerotherapy while they wait on the transplant list. If the variceal hemorrhage cannot be controlled medically in a transplant candidate, then the patient should undergo an emergency shunt procedure. The shunt of choice is a large-bore H-graft
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mesocaval or mesorenal shunt. This shunt effectively controls the acute hemorrhage, is relatively simple to perform, does not adversely impact on the subsequent live~ transplant, and can simply be ligated after the transplant is completed. Patients who experience variceal hemorrhage as the only manifestation of their liver disease should be treated initially with endoscopic sclerotherapy. For that small group of patients who are either not candidates for sclerotherapy or who rebleed despite sclerotherapy, the choice of shunt or transplantation is presently a difficult one, because both therapies provide excellent results in this group of patients. The choice of therapy should be made on an individual basis and only after consultation with both transplant and shunt surgeons. If a shunt is chosen, we prefer the DSRS because it maintains hepatic portal perfusion in many patients and does not require dissection of the porta hepatis. The management of patients with a prior portosystemic shunt at the time of transplantation depends on the type of shunt and the duration of time between the shunt and the transplant. Shunts not involving the hepatic hilum have little adverse impact on the performance of the transplant. There are insufficient data to assess accurately the effect of a prior portacaval shunt on the transplant. However, our clinical experience and that of other transplant groups indicate that the transplantation of these patients is technically more difficult than that of patients with shunts not involving the hilum. With the availability of other shunting procedures that do not involve extensive dissection of the hepatic hilum, there is little role for either end-to-side or side-to-side portacaval shunts in patients who are potential liver transplant candidates. On the other hand, a prior portacaval shunt is not a contraindication to liver transplantation.
REFERENCES 1. Anonymous: Management of acute variceal bleeding. Lancet 2:999, 1985 2. Brems JL, Hiatt JR, Klein AS, et al: Effect of a prior portosystemic shunt on subsequent liver transplantation. Ann Surg 209:51, 1989 3. Busuttil RW, Colonna JO, Hiatt JR, et al: The first 100 liver transplants at UCLA. Ann Surg 206:387, 1987 4. Busuttil RW, Memsic LD, Quinones-Baldrich W, et al: Liver transplantation at UCLA: Program development, organization, initiation, and early results. Am J Surg 152:75, 1986 5. Colonna JO II, Brems JJ, Hiatt JR, et al: The quality of survival after liver transplantation. Transplant Proc 20:594, 1988 6. DiMagno EP, Zinsmeister AR, Larson DE, et al: Influence of hepatic reserve and cause of esophageal varices on survival and rebleeding before and after the introduction of sclerotherapy: A prospective analysis. Mayo Clin Proc 60:149, 1985 7. Esquivel CO, Klintmalm G, Iwatsuki S, et al: Liver transplantation in patients with patent splenorenal shunt. Surgery 101:430, 1987 8. Fleig WE, Stange EF, Hunecke R, et al: Prevention of recurrent bleeding in cirrhotics with recent variceal hemorrhage: Prospective randomized comparison of propranolol and sclerotherapy. Hepatology 7:355, 1987 9. Foley TC, Davis CP, Conway PA: Liver transplant recipients: Self report on symptom frequency, symptom distress, quality oflife. Transplant Proc 21:2417, 1989 10. Friend PJ, Lim S, Smith M, et al: Liver transplantation in the Cambridge/King's College Hospital Series-the first 400 patients. Transplant Proc 121:2397, 1989
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therapy for long-term treatment of variceal bleeding: Early results of a randomized controlled trial. Ann Surg 206:261, 1987 Rikkers LF, Edney JA: Practice of Surgery. Connecticut, Woodbury Press, 1988, p 1 Shaw BW Jr: Exclusion criteria for liver transplant recipients. Transplant Proc, in press Shaw BW Jr, Wood RP, Gordon RD: Influence of selective patient variables and operative blood loss on six-month survival following liver transplantation. Semin Liver Dis 5:385, 1985 Shaw BW Jr, Wood RP, Kaufman SS, et al: Liver transplantation therapy for children. Part 1. J Pediatr Gastroenterol Nutr 7:157, 1988 Shaw BW Jr, Wood RP, Kaufman SS, et al: Liver transplantation therapy for children. Part 2. J Pediatr Gastroenterol Nutr 7:797, 1988 Shaw BW Jr, Wood RP, Stratta RJ, et al: Stratifying the causes of death in liver transplant recipients; An approach to improving survival. Arch Surg, in press Shaw BW Jr, Wood RP, Stratta RJ, et al: Surgical Treatment of Digestive Disease. Chicago, Year Book Medical Publishers, in press Soderlund C, Ihre C: Endoscopic sclerotherapy vs conservative management of bleeding oesophageal varices: A 5-year prospective controlled trial of emergency and long-term treatment. Acta Chir Scand 151:449, 1985 Spence RAJ, Johnston GW: Stapled esophageal transection of varices: Results in 100 consecutive patients. Surg Gynecol Obstet 160:323, 1985 Starzl TE, Van Thiel DH, Tzakis A, et al: Orthotopic liver transplantation for alcoholic cirrhosis. JAMA 260:2542, 1988 Sugiura M, Futugawa S: Esophageal transection with paraesophagogastric devascularization (the Sugiura procedure) in the treatment of esophageal varices. World J Surg 8:673, 1984 Sugiura M, Futagawa S: Results of six hundred and thirty-six esophageal transections with paraesophagogastric devascularization in the treatment of esophageal varices. J Vasc Surg 1:254, 1984 Terblanche J: The surgeon's role in the management of portal hypertension. Ann Surg 209:381, 1989 Terblanche J, Bornman PC, Kahn D, et al: Failure of repeated injection sclerotherapy to improve long-term survival after oesophageal variceal bleeding: A five-year prospective controlled clinical trial. Lancet 2:1328, 1983 Terblanche J, Yakoob HI, Bornman PC, et al: Acute bleeding varices: A five-year prospective evaluation of tamponade and sclerotherapy. Ann Surg 194:521, 1981 The Copenhagen Esophageal Varices and Sclerotherapy Project: Sclerotherapy after first variceal hemorrhage in cirrhosis: A randomized multicenter trial. N Engl J Med 311:1594, 1984 Turcotte JG, Wallin WV Jr, Child CG III: End-to-side versus side-to-side portacaval shunts in patients with hepatic cirrhosis. Am J Surg 117:108, 1969 Van Thiel DH, Tarter RE, Gavalier JS, et al: Liver transplantation in adults: An analysis of costs and benefits at the University of Pittsburgh. Gastroenterology 90:211, 1986 Warren WD, Henderson JM, Millikan WJ, et al: Distal splenorenal shunt versus endoscopic sclerotherapy for long-term management of variceal bleeding. Ann Surg 203:454, 1986 Warren WD, Millikan WJ, Henderson JM, et al: Ten years of portal hypertensive surgery at Emory: Results and perspectives. Ann Surg 195:530, 1982 Westaby D, Macdougall BRD, Williams R: Improved survival following injection sclerotherapy for esophageal varices: Final analysis of a controlled trial. Hepatology 5:827, 1985 'Wood RP, Rikkers LF, Shaw BW Jr, et al: A review of liver transplantation for gastroenterologists. Am J Gastroenterol 82:593, 1987
Address reprint requests to R. Patrick Wood, MD Department of Surgery University of Nebraska Medical Center 42nd and Dewey Avenue Omaha, NB 68105
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Liver Transplantation for Variceal Hemorrhage
R. Patrick Wood, MD, FACS, * Byers W. Shaw, Jr, MD, FACS, t and Layton F. Rikkers, MD*
Theoretically, liver transplantation is the ideal therapy for all patients with chronic liver disease complicated by portal hypertension and variceal hemorrhage. Only by replacing the diseased liver and reestablishing the low-resistance portal outflow through the liver are portal hemodynamics restored to normal. 30 In addition, liver transplantation is the only therapy for bleeding esophageal varices that addresses the underlying liver disease and restores the patient's hepatic functional reserve to normal. Mter successful transplantation, the patient is not only protected from recurrent variceal hemorrhage but also from the complications of encephalopathy and liver failure, which are frequently associated with other therapies for variceal hemorrhage. 36, 38, 40. 52 The use of liver transplantation as a therapy for all patients with chronic liver disease and variceal hemorrhage is, however, limited by a number of factors, including the necessity of a donor liver to perform the procedure, the mortality and morbidity associated with the procedure, the cost of both the procedure and the immunosuppressive medications, and the limited data on the long-term results of liver transplantation. • Important questions regarding the role of liver transplantation in patients with variceal hemorrhage include the following: (1) Which patients with variceal hemorrhage are candidates for liver transplantation? (2) If the transplant is to be delayed, what is the optimal therapy to prevent recurrent variceal hemorrhage and to maintain the option of subsequent transplantation? (3) In a patient who is presently a transplant candidate, how should acute variceal hemorrhage be managed? (4) In transplanting a patient with From the Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska
*Associate Professor· tProfessor :j:Professor and Chairman
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a portosystemic shunt, how does the presence of the shunt influence the transplant operation?
WHICH VARICEAL BLEEDERS ARE CANDIDATES FOR TRANSPLANTATION? It should be emphasized that liver transplantation is not a therapy for variceal hemorrhage but rather a treatment for patients with advanced liver disease. There are a number of diseases that result in portal hypertension and esophageal varices for which liver transplantation is inappropriate (Table 1). In fact, in diseases such as schistosomiasis (probably the most common cause of portal hypertension throughout the world) and portal vein thrombosis, both of which are associated with normal functional hepatic reserve, long-term prevention of variceal hemorrhage by sclerotherapy or a non transplant operation can result in a normal quality and duration of survival. 40 For the remaining patients with chronic liver disease and variceal hemorrhage, however, liver transplantation should be considered among the options for prevention and control of recurrent bleeding. Liver transplantation is indicated for the treatment of selected patients with end-stage liver disease that is medically and surgically intractable. Because there are other means available to treat patients who experience variceal hemorrhage as a complication of their liver disease, the indication for transplantation in this group of patients must be based on a complete assessment of the probability of both short-term and long-term survival and rehabilitation provided by each therapy. The survival rates for the various treatments available to control variceal hemorrhage are dependent on two factors; the etiology of the patient's liver disease and the level of liver dysfunction at the time the therapy is instituted. 6, 12, 19. 41, 42, 45 Patients with alcoholic liver disease, as a group, do worse with most interventions to control variceal hemorrhage when compared with patients with nonalcoholic liver disease. 23, 36, 40 Table 1. Diseases Associated with Portal Hypertension Not Usually Requiring Transplantation Extrahepatic, Presinusoidal 1. Portal vein thrombosis 2. Cavernomatous transformation of the portal vein 3. Splenic vein thrombosis Intrahepatic Presinusoidal 1. Schistosomiasis 2. Sarcoidosis* 3. Congenital hepatic fibrosis* 4. Arsenic toxicity 5. Myeloproliferative diseases Increased Portal Flow 1. Hepatic artery-portal vein fistula 2. Increased splenic flow (idiopathic portal hypertension) *May require transplantation as disease progresses.
r
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A large number of controlled and uncontrolled studies have reported the short-term and long-term results of shunt surgery21, 24, 31, 34, 35, 39, 56, 58 and chronic sclerotherapy. 8, 12, 27, 29, 33, 39, 47, 53-55, 59-60 The survival rates for patients undergoing chronic sclerotherapy range from 50 to 90% at 1 year and 40 to 80% at 5 years, as compared to 70 to 90% at 1 year and 40 to 60% at 5 years for patients undergoing portosystemic shunts. Although almost 90% of all liver transplants have been performed in the last 5 years, there is an extensive literature (with limited follow-up) on the results of liver transplantation. 10, 14, 15, 22, 24, 25, 43, 44, 46, 61 In a recent review of their experience with liver transplantation in patients with variceal hemorrhage, Iwatsuki et aP3 compared their results with liver transplantation in 302 patients to those reported in the literature for other therapies for variceal hemorrhage. The survival rate in the transplanted patients was 79% at 1 year and 71% at 5 years. The difference in survival rates was of greatest magnitude when Child's class C patients who received liver transplants (79% I-year and 71% 5-year survival rates) were compared with Child's C patients who were treated with portosystemic shunts (30 to 70% I-year and 13 to 35% 5-year survival rates). To put this study in perspective, however, it should be emphasized that Iwatsuki's patient population included both children and adults who had almost exclusively nonalcoholic liver diseases. In contrast, the comparison groups were derived from various series of shunted patients made up primarily of adult alcoholic cirrhotics. In addition, only 3% of the transplant patients were actively bleeding from varices at the time of the operation, whereas the patients in the comparison groups were specifically being treated for variceal hemorrhage, many of them in the emergency setting. Although the transplant and non transplant groups are not comparable in this investigation, the following conclusion is valid: in those patients with end-stage liver disease (Child's class C) who are appropriate candidates, liver transplantation provides survival results superior to any other therapy for the control of variceal hemorrhage. In patients with well-compensated liver disease (Child's class A and B patients) who experience a variceal hemorrhage, no such clear-cut recommendatiQl1 can be made. This group of patients will do well initially with any of the available therapies to control the variceal hemorrhage. In one series, the survival rate for Child's class A and B patients treated with sclerotherapy was over 95% at 1 year and over 80% at 5 years. 30 Selective or nonselective shunts in this group of patients yield survival rates of 70 to 90% at 1 year and 50 to 65% at 5 years. 19, 30, 31, 58 By comparison, data from our own center on adult liver transplant patients showed actuarial survival rates following transplantation of Child's class A and B patients of 89% at 1 year and 4 years. Figure 1 compares the survival curves for 168 adult Child's class A, B, and C patients receiving liver transplants at our institution with 348 patients in the Emory University series receiving a selective shunt. 59 The most striking characteristic is that the slope of the survival curves in the transplanted patients is flat after the first year. This indicates that the major mortality associated with transplantation is concentrated in the first year, after which the patients are unlikely to develop fatal complications. In the
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Figure 1. Survival curves for 168 adult Child's class AlB and C patients receiving liver transplants at the University of Nebraska Medical Center compared with 348 adult Child's AI Band C patients receiving selective shunts at Emory University. The actuarial survival curves for the transplanted patients were calculated by the life-table method, whereas the survival curves for the shunted patients were estimated from life-table data presented in Warren et al. 59
shunted patients, the survival curves demonstrate the continued decline in survival over time due to the progressive nature of most patients' liver disease. In addition to comparing survival rates, the therapies for controlling variceal hemorrhage must also be compared for the quality of survival that is provided. Chronic sclerotherapy is associated with a 30 to 60% incidence of rebleeding and a 15 to 30% ultimate failure rate. 19. 28, 36, 38, 40, 52 Nonselective shunts virtually eliminate rebleeding as a complication but are associated with a 40% incidence of severe recurrent encephalopathy. 28,36,38,40 Selective shunts have a lower incidence of encephalopathy (in several studies), a slightly higher incidence of rebleeding compared to nonselective shunts, and a lO% incidence of portal vein thrombosis. 37 In liver transplant patients, the rehabilitation rates following successful transplantation range from 75 to 85%.5, 9, 13, 43, 44, 57
CONTRAINDICATIONS TO LIVER TRANSPLANTATION As results have improved, the indications for transplantation have been liberalized and the contraindications have become fewer. A list of the generally accepted contraindications to transplantation is shown in Table 2. It should be emphasized that this table serves only as a general guideline and that each patient should be evaluated on an individual basis,
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Table 2. Contraindications to Liver Transplantation Absolute Contraindications Extrahepatic malignancy Active sepsis not confined to the liver or biliary system Thrombosis of the entire portal venous system Presence of potentially fatal organ system failure not expected to improve following transplantation Active alcohol or drug abuse Acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) Confirmed and repetitive history of noncompliance Relative Contraindications Extremes of age Positive AIDS serology in an asymptomatic patient Questionable history of noncompliance Multiple prior transplants
Malignancy that is not confined to the liver and overt systemic sepsis are two absolute contraindications to transplantation. In addition, complete thrombosis of the entire portal venous system (portal vein, splenic vein, and superior mesenteric vein) makes transplantation technically impossible. Because the goal of transplantation is to restore the patient to an acceptable quality of life, the presence of other life-threatening conditions that would not be expected to improve following transplantation (such as severe coronary artery disease or pulmonary disease) is also an absolute contraindication to transplantation. Active alcohol or drug abuse, the acquired immune defiCiency syndrome (AIDS), and the AIDS-related complex have also been considered absolute contraindications. Finally, a history of noncompliance with medication schedules and follow-up medical care may eliminate the patient from consideration as a candidate for transplantation. Alcoholic cirrhosis is the most frequent cause of end-stage liver disease in this country.40 In the past, active alcohol abuse was considered a contraindication to transplantation. However, a limited number of patients with alcoholic liver disease who have been abstinent for varying periods have undergone transplantation with results comparable to those obtained in most varieties of nonalcoholic liver disease. 23 Recently, Starzl et al49 have challenged the concept of not considering active alcoholics for liver transplantation. They have shown no difference in survival of active alcoholics compared to patients transplanted for nonalcoholic liver diseases. If transplantation does become the accepted form of therapy for patients with acute alcoholic hepatitis and chronic alcohol-induced liver disease, this will greatly expand the pool of potential recipients for the already scarce resource of liver donors.
EMERGENCY MANAGEMENT OF VARICEAL HEMORRHAGE Endoscopic sclerotherapy will control 80 to 90% of patients with acute variceal bleeding, with failure defined as persistent hemorrhage after two injection sessions. Terblanche54 has shown that mortality among the 10 to 20% of patients in whom sclerotherapy fails is excessive unless surgical
intervention is undertaken. The surgical procedures to choose from include portosystemic shunt, gastric devascularization, and liver transplantation. 1 If the patient is already on a waiting list as a transplant candidate, he or she should be transferred to the transplant center if possible. This will allow the greatest number of options for the patient, including emergency transplantation should a donor liver become available. Emergency transplantation will provide definitive control of bleeding varices but is limited by the availability of donor organs on an emergency basis. If a donor organ is not immediately available and surgical intervention is indicated, the procedure chosen should be one with which the surgeon has familiarity and that does not compromise subsequent transplantation. The simplest operation is esophageal transection with an end-to-end stapling device. 20, 32, 48 Other gastric devascularization procedures can be used if the surgeon has experience with such techniques. 16, 26, 50, 51 However, portal decompression more reliably controls variceal hemorrhage and has the advantage of preventing further bleeding episodes. Shunts that avoid the porta hepatis and that can be ~ompleted expeditiously are preferred. In this setting, large-bore interposition mesocaval or mesorenal shunts are advisable. If a portacaval shunt is chosen, an end-to-side portacaval anastomosis is preferable to a side-to-side shunt because the former is generally easier to perform and does not risk compromising the length of extrahepatic portal vein available for subsequent transplantation. If done carefully, portacaval shunt does not prohibit subsequent transplantation. In some ways, the dissection necessary to perform the shunt lessens the difficulty of subsequent transplantation. In treating a patient who is a recognized transplant candidate, there is little need to consider selective shunting because the apparent advantages over nonselective shunts are only realized in the long term. Short-term disadvantages of selective shunts include an increased risk of portal vein thrombosis, incomplete portal decompression, prolonged operating time, and exacerbation of ascites. 37 The more difficult issue concerns the management of the patient whose candidacy for transplantation must be assessed for the first time in the setting of acute variceal hemorrhage. As we have indicated, the choice of surgical procedure is influenced by whether or not the patient will eventually undergo transplantation. Patients who are questionable candidates for transplantation should not undergo this operation in an emergency situation. In addition to those patients with one or more of the contraindications listed earlier, exceptions to emergency transplantation include active alcoholics whose rehabilitation potential has not been assessed, patients in whom the cause of portal hypertension remains unknown, and Child's class A patients who are not yet clearly in need of transplantation. These patients should be treated with one of the nontransplant procedures, and the choice should be made with the assumption that the patient will be a subsequent transplant recipient. The patient can be stabilized and evaluated as a transplant candidate more carefully at a later date.
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VARICEAL HEMORRHAGE IN THE PATIENT WITH GOOD HEPATIC FUNCTIONAL RESERVE An unanswered question is what therapy is most appropriate for that select group of patients who experience a variceal hemorrhage but have minimal or no evidence of liver dysfunction and whose bleeding can initially be controlled medically. Because the incidence of rebleeding following an initial episode of variceal hemorrhage is at least 70%, some therapeutic intervention to prevent recurrent hemorrhage seems warranted. Randomized trials of sclerotherapy versus shunt surgery suggest that endoscopic variceal sclerosis is an appropriate initial therapy in this group of patients with either shunt surgery or transplantation reserved for sclerotherapy failures. 39, 58 Some patients, however, are not candidates for initial management with sclerotherapy. These include the following: (1) patients who bleed from gastric varices, (2) patients with bleeding from portal hypertensive gastropathy, (3) noncompliant patients, and (4) individuals who live in remote areas where a rebleeding episode may be fatal owing to limited access to medical facilities. 39 Patients who are not candidates for initial management with sclerotherapy and those patients who fail sclerotherapy should be considered candidates for either shunt surgery or transplantation. In selecting a patient for either a distal splenorenal shunt (DSRS) or transplantation, the group at Emory3° uses a variety of tests, including liver volume and galactose elimination capacity, to identify those patients whose hepatic reserve is sufficiently limited to warrant proceeding with transplantation. Shunts are reserved for good-risk patients. These investigators believe that their data ". . . show that selective shunt is the surgical procedure of choice in Child's AlB cirrhotics who fail sclerotherapy because it is safer (lower operative mortality), less expensive, and carries no risk of chronic immunosuppression." However, their data do not support this broad generalization. As shown in Figure 1, the early mortality associated with the transplantation of Child's A and B patients is higher than with selective shunts, but this difference is no longer apparent at 18 months. Beyond 18 months, the survival curve remains flat for the transplanted patients but continues to progressively decline in the shunted patients. Although the cost of a liver transplant is substantially greater than that of a DSRS, the successfully transplanted patient has an excellent prognosis both for survival and for a normal quality of life. In contrast, the majority of patients receiving a shunt will experience progressive deterioration of hepatic function and will eventually require a liver transplant for long-term survival. Although transplanted patients are at risk for complications related to the prolonged use of immunosuppression, these complications become less likely over time as the dosages of immunosuppressive medication are reduced to maintenance levels. This is in contrast to the complications of progressive liver disease faced by patients who receive a shunt. There is no single test or series of tests that provide definitive criteria to identifY those patients who will be best treated with a shunt versus those who should undergo a transplant. Rather, the decision to shunt or transplant must be made on a case-by-case basis. In our institution, patients with
variceal hemorrhage but well-compensated liver disease undergo a complete evaluation by the transplant team, the shunt surgeon, and our adult gastroenterology group. If a shunt is selected, the transplant team is kept informed of the patient's postoperative course and consulted if the patient's hepatic function deteriorates at any point following the shunt. Patients who manifest signs or symptoms of progression of their liver disease are reevaluated by the transplant service and, if indicated, are activated as candidates for transplantation. If a decision is made to proceed with a shunt, we prefer the DSRS if anatomy allows and the patient does not have medically intractable ascites. This shunt effectively controls bleeding and has an excellent long-term patency rate. In addition, four of seven controlled studies have reported a lower incidence of encephalopathy following DSRS than after nonselective shunts. 37 An additional advantage of the DSRS is that the hepatic hilum is not dissected and the presence of a DSRS does not adversely affect the performance of a subsequent liver transplant. Patients who undergo a successful shunt operation should be monitored at 6-month intervals to identify any signs of progressive liver dysfunction. The successful control of variceal hemorrhage does not eliminate the need for close follow-up in potential transplant candidates who receive a DSRS. The goal should be to refer patients for transplantation while they remain a low risk and have the greatest chance of a successful result.
LIVER TRANSPLANTATION IN THE PATIENT WITH A PORTOSYSTEMIC SHUNT Over the past 49 months, we have transplanted 203 adult patients, 11 of whom have had prior portosystemic shunts. Six patients had nonselective shunts (two end-to-side portacaval, two mesorenal, two mesocaval, and one central splenorenal), and five individuals had selective shunts (all DSRS). The shunts had been performed from 1 month to 26 years prior to the transplant. Nine of the 11 (81%) patients survived and were discharged from the hospital. Iwatsuki et a}23 also failed to show Significant differences in outcome between previously shunted and unshunted patients after hepatic transplantation. In individual cases, however, prior portosystemic shunts (especially the portacaval variety) can compromise the transplant operation. In the discussion that follows, we present our approach to the preoperative evaluation of patients with prior portosystemic shunts and the intraoperative management of these patients during the transplant procedure. Preoperative Assessment Patients with a prior portosystemic shunt should have the patency of their shunt determined with duplex ultrasonography. If ultrasonography demonstrates patency in a patient with a nonselective shunt, no further evaluation of the shunt is required. However, some transplant centers recommend both selective mesenteric angiography and venography of the inferior vena cava to evaluate a nonselective shunt. 2 , 7 Initially, we used duplex ultrasonography to assess the patency of a DSRS, and we removed
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the spleen in all patients with a patent DSRS. However, one of our patients with a DSRS developed portal vein thrombosis in the immediate posttransplant period secondary to extensive collateralization into the splenic vein remnant. We now obtain mesenteric angiograms on all patients with a patent DSRS. When extensive collateralization to the shunt is present, we believe that a splenectomy alone may be inadequate to "disconnect" the shunt. Intraoperative Management Whether a portacaval shunt was performed in an end-to-side or sideto-side fashion, the operative approach at the time of transplantation is the same: the infrahepatic inferior vena cava (IVe) and portal vein proximal and distal to the shunt must be controlled. If there is an adequate length of the Ive between the shunt and the liver to allow the placement of a vascular clamp, the shunt is left intact, the native liver is removed, and the suprahepatic and infrahepatic caval anastomoses are performed. As the shunt provides portal decompression, the portal vein limb of the venous bypass system is not required during the anhepatic phase of the transplant. After the infrahepatic IVe anastomosis has been completed, a vascular clamp is placed on the lve across the shunt and a second clamp is placed on the proximal portal vein. The shunt is then transected, leaving a cuff of portal vein on the lve. The anastomotic site in the IVe is oversewn, and the portal vein anastomosis is completed in the usual end-to-end fashion. If there is insufficient length of infrahepatic lve bet~een the shunt and the liver to place a vascular clamp safely, the transplant surgeon has two options. The first option is to proceed as previously described and, after completion of the suprahepatic IVe anastomosis, dismantle the shunt. In this case, the portal vein limb of the venous bypass would not be used and there would be no decompression of the portal venous system during the infrahepatic lve and portal vein anastomoses. The second option is to dismantle the shunt before the native liver is removed and to place the portal vein cannula of the venous bypass as is done routinely for all adult transplants. This option requires that the portal vein be of sufficient length and caliber to accommodate the portal vein cannula. A patent mesorenal or mesocaval shunt need not be disturbed during the initial dissection of the native liver. In addition, because the shunt decompresses the portal venous system, there is no need for the portal vein limb of the venous bypass system during the anhepatic phase of the transplant operation. Because this is a total shunt, it must be isolated and ligated prior to the completion of the transplant procedure. Unlike a mesocaval or mesorenal shunt, a patent central splenorenal shunt requires that the splenic vein be identified and isolated at the level of its junction with the portal vein before the patient is placed on venous bypass and the native liver is removed. The presence of the shunt, however, does not increase the technical difficulty of the initial dissection of the recipient's liver, although the isolation of the splenic vein may be tedious. There is no need for the portal vein limb of the venous bypass during the anhepatic phase, because this shunt provides adequate portal decompres-
sion. However, it is important that the shunt be ligated after the portal vein anastomosis is completed. This is usually accomplished by doubly ligating the previously isolated splenic vein just before its junction with the portal vein. The presence of a DSRS does not increase the difficulty of the transplant procedure because the hepatic hilum is not disturbed during the performance of the shunt. This shunt, in theory, does not provide decompression for the mesenteric side of the portal circulation, and the portal vein limb of the venous bypass must be inserted to decompress the portal venous system during the anhepatic phase. There are differing opinions regarding the management of a DSRS once the new liver has been implanted. Brems et aF recommend that the shunt not be disturbed. They have had no complications with this approach in two patients. The Pittsburgh group7 recommends both a splenectomy and ligation of the shunt at the level of the renal vein. They were able to perform a splenectomy in all four of their patients transplanted with a patent DSRS; in three of the four, the shunt was also ligated. However, one of these individuals developed pancreatitis and a pancreatic fistula secondary to dissection of the shunt. In all five of our patients transplanted with a patent DSRS, splenectomy was performed and no attempt was made to ligate the shunt. One patient, described previously, developed a portal vein thrombosis due to extensive collaterals into the splenic vein remnant. In addition to the mesenteric angiogram obtained preoperatively, after the donor liver has been implanted, a contrast study of the portal venous system is obtained by cannulating a vein in the mesentery of the proximal jejunum. If the portal vein is well visualized (indicating preferential flow of the contrast toward the liver), the shunt may be left undisturbed. If there is nonvisualization of the portal vein, then a splenectomy is performed and an attempt is made to ligate the collaterals between the mesenteric portal system and the remnant of the shunt.
SUMMARY At the present time, liver transplantation must be considered among the treatment options for patients with variceal hemorrhage. For a significant percentage of variceal bleeders throughout the world, however, transplantation is not a viable option either because the patient is not an appropriate transplant candidate or because of the etiology of the patient's portal hypertension. Sclerotherapy and portosystemic shunts remain the mainstay of therapy for these patients. The survival rates with liver transplantation are superior to those reported for other therapies for variceal hemorrhage in patients who have moderate or severe liver disease in addition to variceal hemorrhage. Child's C patients whose variceal hemorrhage is controlled medically should be evaluated for transplantation and receive chronic sclerotherapy while they wait on the transplant list. If the variceal hemorrhage cannot be controlled medically in a transplant candidate, then the patient should undergo an emergency shunt procedure. The shunt of choice is a large-bore H-graft
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mesocaval or mesorenal shunt. This shunt effectively controls the acute hemorrhage, is relatively simple to perform, does not adversely impact on the subsequent live~ transplant, and can simply be ligated after the transplant is completed. Patients who experience variceal hemorrhage as the only manifestation of their liver disease should be treated initially with endoscopic sclerotherapy. For that small group of patients who are either not candidates for sclerotherapy or who rebleed despite sclerotherapy, the choice of shunt or transplantation is presently a difficult one, because both therapies provide excellent results in this group of patients. The choice of therapy should be made on an individual basis and only after consultation with both transplant and shunt surgeons. If a shunt is chosen, we prefer the DSRS because it maintains hepatic portal perfusion in many patients and does not require dissection of the porta hepatis. The management of patients with a prior portosystemic shunt at the time of transplantation depends on the type of shunt and the duration of time between the shunt and the transplant. Shunts not involving the hepatic hilum have little adverse impact on the performance of the transplant. There are insufficient data to assess accurately the effect of a prior portacaval shunt on the transplant. However, our clinical experience and that of other transplant groups indicate that the transplantation of these patients is technically more difficult than that of patients with shunts not involving the hilum. With the availability of other shunting procedures that do not involve extensive dissection of the hepatic hilum, there is little role for either end-to-side or side-to-side portacaval shunts in patients who are potential liver transplant candidates. On the other hand, a prior portacaval shunt is not a contraindication to liver transplantation.
REFERENCES 1. Anonymous: Management of acute variceal bleeding. Lancet 2:999, 1985 2. Brems JL, Hiatt JR, Klein AS, et al: Effect of a prior portosystemic shunt on subsequent liver transplantation. Ann Surg 209:51, 1989 3. Busuttil RW, Colonna JO, Hiatt JR, et al: The first 100 liver transplants at UCLA. Ann Surg 206:387, 1987 4. Busuttil RW, Memsic LD, Quinones-Baldrich W, et al: Liver transplantation at UCLA: Program development, organization, initiation, and early results. Am J Surg 152:75, 1986 5. Colonna JO II, Brems JJ, Hiatt JR, et al: The quality of survival after liver transplantation. Transplant Proc 20:594, 1988 6. DiMagno EP, Zinsmeister AR, Larson DE, et al: Influence of hepatic reserve and cause of esophageal varices on survival and rebleeding before and after the introduction of sclerotherapy: A prospective analysis. Mayo Clin Proc 60:149, 1985 7. Esquivel CO, Klintmalm G, Iwatsuki S, et al: Liver transplantation in patients with patent splenorenal shunt. Surgery 101:430, 1987 8. Fleig WE, Stange EF, Hunecke R, et al: Prevention of recurrent bleeding in cirrhotics with recent variceal hemorrhage: Prospective randomized comparison of propranolol and sclerotherapy. Hepatology 7:355, 1987 9. Foley TC, Davis CP, Conway PA: Liver transplant recipients: Self report on symptom frequency, symptom distress, quality oflife. Transplant Proc 21:2417, 1989 10. Friend PJ, Lim S, Smith M, et al: Liver transplantation in the Cambridge/King's College Hospital Series-the first 400 patients. Transplant Proc 121:2397, 1989
n. 12. 13. 14. 15. 16. 17. 18.
19. 20. 21. 22. 23. 24. 25. 26. 27. 28.
29. 30. 31.
32.
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34. 35.
36. 37. 38. 39.
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