Surgical Shunt Versus TIPS for Treatment of Variceal Hemorrhage in the Current Era of Liver and Multivisceral Transplantation

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Guilherme Costa, MD , Ruy J. Cruz Jr, MD, PhD , Kareem M. Abu-Elmagd, MD, PhD *

KEYWORDS Portal hypertension Portomesenteric venous thrombosis Surgical shunt Transjugular intrahepatic portosystemic shunt Multivisceral transplant Hypercoagulable status

Variceal hemorrhage occurs as a result of portal hypertension due to different underlying diseases such as portal vein thrombosis (prehepatic), liver cirrhosis (hepatic), and Budd-Chiari syndrome (posthepatic). 1,2 The interplay between the portal hemodynamic changes and hepatic reserve ( Table 1 ) plays a major role in the short and long-term management of these complex patients. Of the important observed hemodynamic changes, is the increase in the intrahepatic vascular resistance compounded by the vasoconstrictor effect of a deficient state of intrahepatic nitric oxide. Of the major sequelae are the development of portosystemic collaterals, gastroesophageal varices, and a chronic state of systemic hyperdynamic syndrome. 3–7 The natural history of the underlying liver disease is another major factor that should be considered for the establishment of the management algorithm of these patients. Ethanol abuse, chronic viral hepatitis, and cholestatic/autoimmune disorders are the most common liver diseases that significantly influence the long-term outcome with the currently available different therapeutic modalities that are discussed herein. Another important factor that further complicates the management plan of these complex patients is the presence of extensive splenic and portomesenteric venous

Intestinal Rehabilitation and Transplantation Center, Thomas East Starzl Transplantation Insti- tute, Department of Surgery, University of Pittsburgh Medical Center, UPMC Montefiore – 7 South, 3459 Fifth Avenue, Pittsburgh, PA 15213-2582, USA * Corresponding author. E-mail address: [email protected]

Table 1 Child-Pugh classification

1 2 3 Albumin (g/dL) >3.5 2.8–3.5 <2.8 Bilirubin (mg/dL) <2 2–3 >3 Prothrombin time a 1–3 4–6 >6 Encephalopathy None 1–2 3–4 Ascites None Slight Moderate

Child-Pugh A 5 5–6 points: excellent hepatic reserve; Child-Pugh B 5 7–9 points: good hepatic reserve; Child-Pugh C 5 10–15 points: poor hepatic reserve. a Seconds prolonged.

thrombosis that develops in cirrhotics and in hypercoagulable patients with normal hepatic parenchyma. Recent advances in pharmacologic and endoscopic management of gastroesophageal variceal bleeding has significantly shifted the main paradigm of therapy from surgical to medical management. 8–14 However, medical failure does occur with an incidence of 20%, which requires radiologic or surgical intervention to decompress the portal system as a palliative but life-saving procedure. Nonetheless, organ replacement with liver alone or a multivisceral graft is the ultimate and definitive treatment for these patients. 13–15 In this article, a management algorithm is outlined to guide and optimize therapy for acute and recurrent variceal bleeding in these unique patients.

EVALUATION GUIDELINES The standard evaluation process of patients with variceal bleeding has been compre- hensively addressed in the literature. 9–13 However, special emphasis should be placed on the history of the gastrointestinal hemorrhage including the number and severity of episodes. Documentation of the source of bleeding and the location of varices must be established to exclude other sources and guide therapy. The presence of gastric varices in the absence of Food and Drug Administration approval to use cyanoacrylate in the United States limits the therapeutic use of endoscopic therapy and calls for radiologic or surgical intervention. 11 The role of new endoscopic techniques including the recently introduced endoscopic capsule has increased the accuracy of variceal detection, particularly in patients with enteric and ectopic varices. The diagnosis of portal hypertensive gastropathy and/or colopathy, in the absence of gastrointestinal varices, may also shed some light on the source of bleeding and guide further therapy. The status of portal hypertension can be semiquantitatively assessed by the degree of the pancytopenia, splenomegaly, and radiologic evidence of intra-abdominal visceral collaterals in addition to the endoscopic documentation of gastrointestinal varices, gastropathy, and/or colopathy. Noninvasive radiologic studies could also be helpful as a screening test for the possible coexistence of splenic or portomesenteric venous thrombosis. In persons with radiologic evidence of partial or complete visceral venous thrombosis, a hypercoagulable syndrome must be suspected and thoroughly evaluated. The evaluation process includes measurement of protein C, protein S, antithrombin III, and total homocysteine serum levels. In addition, genetic studies for factor V Leiden, prothrombin G20210A, and JAK-2 gene mutations should be conducted. Equally important are the diagnosis of paroxysmal nocturnal Surgical Shunt Versus Tips 893 hemoglobinuria and the detection of anticardiolipin, lupus anticoagulant, and anti- phospholipid antibodies. When portomesenteric venous thrombosis is suspected or the pattern of gastroesophageal varices is unusual, particularly in the presence of normal liver parenchyma, patients must undergo visceral angiographic studies to evaluate the extent of thrombosis and to map the collateral circulation, including the assessment of the extent of collateralization and direction of flow ( Fig. 1 ). The angiographic studies include superior mesenteric and splenic arterial injections with venous phases. On multiple occasions in their practice, the authors have observed unexpected angiographic findings such as arterial varices, arteriovenous malformations, and intrahepatic arterioportal communications. The old technique of measuring the portal venous pressure through a transsplenic, transhepatic, or transvariceal approach has been abandoned. In selected patients, catheterization of the hepatic veins with measurement of the free and wedged hepatic venous pressure is used, particularly in those with gastroesophageal varices in the absence of significant liver disease or portomesenteric venous thrombosis. Finally, the etiology and extent of liver disease can be easily assessed in a systematic way, including thorough medical history, biochemical and hematological studies, abdominal imaging and, if necessary, percutaneous or transjugular liver biopsy. The histopathologic examination is of utmost importance, particularly in Child A/B patients who could be managed by radiologic or surgical intervention.

VARICEAL DECOMPRESSION WITHOUT ORGAN REPLACEMENT Surgical Shunts With a long-standing history of more than a half of a century, surgical shunts have played a major rule in the management of variceal bleeding by total, partial, selective, or super-selective decompression of the portal, mesenteric, splenic, and gastroesophageal variceal venous system; respectively. Since its peak popularity during the 1960s through the 1980s, surgical shunts have been gradually used with less

Fig. 1. Superior mesenteric arteriogram with delayed venous phase. Note complete occlusion of the superior mesenteric and portal veins. The patient was hypercoagulable and underwent a multivisceral transplantation. 894 Costa et al

frequency because of the introduction or revisiting of new nonsurgical therapeutic modalities and the evolution of abdominal organ transplantation. Total portal systemic shunts are shunts that totally decompress the portal system with surgical anastomosis between the portal vein or one of its major branches, and the vena cava or one of its major tributaries. These shunts have usually been made as a side-to-side shunt with 10 or more millimeters of diameter, with decompression of the whole splanchnic portal hypertensive bed and the high hepatic sinusoidal pressure. Such shunts have a high patency rate, and excellent control of variceal bleeding as well as ascites. 16,17 However, most of the published series document a high incidence of encephalopathy and variable long-term survival outcome, which could be attributed to the differences in the severity and nature of the underlying liver disease among the selected study population. 18 Because of the potentially prohibitive risk of encephalopathy with total shunts, Sar- feh and colleagues 19 popularized partial portal systemic shunts in the 1980s and 1990s by reducing the diameter of the shunt to 8 mm. The rationale is to maintain some portal flow to the hepatocyte without compromising the therapeutic decompression of the varices. 18–20 Technically, the shunt can be easily performed by placing an 8-mm polytetrafluoroethylene-reinforced graft between the portal vein and inferior vena cava ( Fig. 2 ). Data that were published in the 1990s documented excellent control of bleeding with a low risk of encephalopathy and acceptable rate of long- term survival. The shunt has also been compared with the transjugular intrahepatic portosystemic shunt (TIPS) procedure in a randomized trial, as discussed later. Selective decompression of the gastroesophageal varices was achievable by the clinical introduction of the distal splenorenal shunt (DSRS) by Warren and colleagues. 21–23 The shunt selectively decompresses the gastroesophageal varices through the short gastric veins into the splenic venous system and subsequently into the systemic circulation via the left renal vein. With proximal disconnection of

Fig. 2. Schematic diagram of portacaval H-graft. ( From Sarfeh I, Rypins EB, Mason GR. A systematic appraisal of portacaval H-graft diameters. Clinical and hemodynamic perspectives. Ann Surg 1986;204(4):358; with permission.) Surgical Shunt Versus Tips 895 the splenic vein from the portal circulation, the state of portal hypertension is main- tained in the superior mesenteric and portal venous system with preservation, in prin- ciple, of the portal flow to the cirrhotic liver. However, such a compartmentalization and selective variceal decompression was an enigma because of the gradual development of collateralization between the two, high and low, pressure systems that are contained in one celomic cavity. 24 These collaterals were identified as gastric, colon-splenic, and pancreatic ( Fig. 3 A). Accordingly, technical modification of the procedure was required to minimize the development of collaterals between the portal and shunt circulation by adding a complete splenopancreatic disconnection to the standard operation (see Fig. 3 B). 25 Nonetheless, most series that were published in the 1980s and 1990s proved the therapeutic efficacy of the procedure, with low incidence of recurrent variceal bleeding (5%–8%), acceptable risk of hepatic encephalopathy (5%–15%), and excellent long-term survival. 22,23,26 These results reflected the outcome in low-risk Child A/B patients with stable liver disease, particularly those with nonalcoholic and nonhepatic cirrhosis. The popularity of the procedure, however, was limited by different anatomic and technical obstacles that imposed significant surgical challenges. With the increased use and popularity of the TIPS procedure during the late 1990s, particularly among Child A/B variceal bleeders, a multicenter randomized trial sponsored by the National Institutes of Health was conducted, which compared the radiologic shunt with the DSRS among variceal bleeders with preserved hepatic functions. The results are discussed in the section Published Data. 26 With the loss of DSRS selectivity within the first 6 months after surgery, Inokuchi and colleagues 27,28 introduced the coronocaval shunt as a super-selective shunt procedure with direct decompression of the gastroesophageal varices into the systemic circulation. The operation did not gain popularity among the surgical community because of the technical difficulty and the wide variations in the anatomic and hemodynamic pattern of the left gastric venous system among variceal bleeders. A modification of most of the aforementioned shunt procedures has been used at the authors’ center for patients with portomesenteric and splenic venous thrombosis who developed collaterals that are technically amenable for surgical shunting. On multiple occasions, the authors used the coronary, gastroepiploic, and other unnamed collaterals. In these challenging patients, complete gastric devascularization has been

Fig. 3. (A) The distal splenorenal shunt with the pancreatic sump that develops in the pancreatic region siphoning the portal blood flow to the distal splenic segment. ( B) Distal splenorenal shunt with complete splenopancreatic disconnection. ( From Warren WD, Milli- kan WJ, Henderson JM, et al. Splenopancreatic disconnection: improved selectivity of distal splenorenal shunt. Ann Surg 1986;204(4):347; with permission.) 896 Costa et al

a useful surgical alternative, with excellent long-term outcome and very low risk of rebleeding ( Fig. 4 ).

Radiologic Shunt TIPS is a ‘‘minimally invasive’’ procedure that provides direct portal decompression by creating an intrahepatic shunt between the high-pressure portal system and the low- pressure hepatic venous circulation ( Fig. 5 ). With advances in technology, the early reported high-shunt thrombosis was significantly reduced by using covered stents, with reduction in the overall reintervention rate resulting from stenosis and/or thrombosis. Overall, TIPS has been associated with increased risk of stenosis and/or thrombosis, with a 20% or more rebleeding rate. Therefore, follow-up and management protocols have been adopted for prompt reintervention to avoid such a life- threatening complication. The therapeutic efficacy of the procedure has been evaluated in two prospective randomized trials comparing TIPS with the commonly used shunt procedures: the Sarfeh 8-mm portacaval H-graft shunt and the Warren DSRS.

Published Data This section focuses on the most recent results of two major randomized clinical trials that have been conducted comparing the two commonly used surgical shunts with the TIPS procedure.

Portacaval H-graft (8 mm) shunt versus TIPS With nonconventional randomization, the study was initiated in 1993, with 50% of the study population being Child class C variceal bleeders with a mean age of 54 years. 29 All patients had failed initial therapy with pharmacologic and endoscopic management. The underlying liver disease was alcoholic cirrhosis in 60% of the patients, with a mean Model of End-Stage Liver Disease (MELD) score of 14. With similar distribution of risk factors among both groups, TIPS was associated with a significantly higher risk of variceal rebleeding (30%) with no single example of recurrent variceal hemorrhage among the surgical shunt group. 20,29 Reintervention, however, was required in both cohorts with a lower rate (11%) after surgical shunt compared with TIPS (48%). The metabolic impairment of both shunt procedures was measured by the development of new-onset hepatic encephalopathy, which

Fig. 4. (A) Computed tomography (CT) with visualization of extensive gastric wall collaterals in a patient with life-threatening recurrent episodes of bleeding gastric varices caused by portomesenteric venous thrombosis. ( B) Radiologic evidence of decompressed gastric wall varices 1 week after complete gastric devascularization. Surgical Shunt Versus Tips 897

Fig. 5. (A) Splenic arteriogram with delayed venous phase 1 month after TIPS with patent shunt. Note preferential flow of the splenic venous return through a large gastroesophageal coronary collateral. ( B) Successful occlusion of the collateral with an Amplatzer Vascular Plug to reduce the risk of recurrent bleeding and TIPS thrombosis by improving the portal venous flow through the TIPS. was similar in both groups with an incidence of 3% among the surgical group and 4.5% among the TIPS patients. Ascites, at late follow-up, was also lower in the surgical (28%) compared with the TIPS (40%) patients. These results are summarized in Table 2 . As expected, particularly among Child C cirrhotics, the hospital mortality was higher (20%) with surgical shunt compared with the minimally invasive TIPS procedure (15%). Because both procedures are, at best, palliative measures and the study population was mostly alcoholics with Child C cirrhosis, late mortalities with a mean

Table 2 Outcomes at a median follow-up of 8.3 years in trial of 8-mm H-graft portosystemic shunt versus TIPS

8-mm H-graft TIPS (N 5 66) (N 5 66) P Rebleeding: Variceal 0 (0%) 20 (30%) <.01 Gastric 5 (7.6%) 0 (0%) Reintervention 7 (11%) 32 (48%) <.01 Encephalopathy (new) 2 (3%) 3 (4.5%) NS Ascites 18 (28%) 26 (40%) NS Mortality: Hospital 13 (20%) 10 (15%) NS Late 49 (74%) 48 (73%) NS Transplants 1 6

Abbreviation: NS, not significant. Data from Rosemurgy AS, Bloomston M, Clark WC, et al. H-graft portacaval shunts vs TIPS; 10 year follow-up of a randomized trial with comparison to predicted survivals. Ann Surg 2005;241:238–46. 898 Costa et al

follow-up of 8.3 years were unacceptably high in both groups, with 74% death rate after surgical shunt and 73% after TIPS (see Table 2 ). Of note, transplantation was used as a rescue therapy in only 7 of the randomized patients, with 1 example after surgical shunt and 6 after TIPS.

DSRS versus TIPS The study was a well-designed prospective randomized multicenter trial funded by the National Institutes of Health and initiated in 1996. 26,30 There were 5 participating centers, namely Cleveland Clinic, Emory University, University of Wisconsin, University of Miami, and University of Pittsburgh. The study included a total of 140 Child class A (60%) and B (40%) patients, with a mean age of 53 Æ 10 years and a male/female ratio of 3:2. Failure of endoscopic or pharmacologic therapy to prevent recurrent variceal bleeding was documented in all of the enrolled patients. The primary liver disease was alcoholic cirrhosis in 60% of the patients, with a mean MELD score of 9.8. The primary end points were rebleeding and hepatic encephalopathy with the secondary end points being death, ascites, need for transplant, progression of liver disease, quality of life, and cost. All these end points and other pertinent related medical information were prospectively reviewed and periodically documented by different specialized review committees and agreed on by consensus. Very strict criteria for reintervention were defined from the outset, which guided the decision-making process for either dila- tation or restenting of the shunt particularly of the TIPS procedure. As shown in Table 3 and Fig. 6 , there was no significant difference in the overall incidence and cumulative risk of the two primary end points. However, the rebleeding rate was relatively higher (10.5%) after TIPS compared with DSRS (5.5%). Unexpectedly, the overall incidence of encephalopathy was similar among both groups. However, many of these episodes were isolated single events that were successfully treated with simple medical measures. With no significant difference in the overall incidence, DSRS patients had a higher rate of early postoperative ascites while more of the TIPS

Table 3 Results of the National Institutes of Health Multicenter Randomized Study

DSRS TIPS Parameter (N 5 73) (N 5 67) Significance Rebleeding 5.5% 10.5% NS Encephalopathy 50% 50% NS Survival: 2 years 81% 88% NS Survival: 5 years 62% 61% NS Thrombosis/stenosis 11% 82% P<.001 Ascites 21 (29%) 17 (25%) NS Need for transplant 6 (8%) 8 (12%) NS Quality of life SF36 a Physical component 41.7 42.1 NS Mental component 44.3 44.2 NS Costs $28,734 $21,607 NS

Abbreviation: NS, not significant. a Normal scores for physical and mental components for SF36 are 50. Data from Henderson JM, Boyer TD, Kutner MH, et al. Distal splenorenal shunt versus transjugular intrahepatic portal systematic shunt for variceal bleeding: a randomized trial. Gastroenterology 2006;130:1643–51. Surgical Shunt Versus Tips 899

Fig. 6. Kaplan-Meier curves for the main end points in the DIVERT Trial. Variceal rebleeding, first hepatic encephalopathy episode, and survival show no significant difference at any time point to 5 years. The reintervention rate was significantly ( P<.001) greater in the TIPS group than in the DSRS group at all time points. ( From Henderson JM, Boyer TD, Kutner MH, et al. Distal splenorenal shunt versus transjugular intrahepatic portal systematic shunt for variceal bleeding: a randomized trial. Gastroenterology 2006;130:1647; with permission.) patients developed ascites with long-term follow-up, particularly those who experi- enced progressive liver failure. The transplantation rate was 8% after DSRS and 12% after TIPS. One of the most important findings in the study, as shown in Fig. 6 , is the significant higher reintervention rate with TIPS (82%) compared with DSRS (11%). It is obvious from the Kaplan-Meier cumulative reintervention-free curve that the events after DSRS occurred during the early postoperative period, whereas those after TIPS continued to occur throughout the study period. These data support the current recommendation of careful monitoring of long-term TIPS patency. Both DSRS and TIPS were associated with similar short and long-term survival, as shown in Fig. 7 , with approximately 2- and 5-year survival of 85% and 62%, respectively. The causes of death were variable and the subset analysis showed no significant difference in mortality by Child-Pugh class score, procedural related, liver disease related, and other causes of death between the DSRS and TIPS groups. 30 The quality of life measured by the Short Form-36 score at 1 year after both procedures is shown in Table 3 , with similar results. Of note, the preliminary as well as the most recent update of cost analysis showed that TIPS is as cost-effective as DSRS in preventing variceal rebleeding in patients who failed medical therapy. 31

ABDOMINAL ORGAN TRANSPLANTATION Liver Transplantation Hepatic transplantation is no longer used as an emergency procedure for active variceal bleeding. 32 This is mostly because of the current shortage in cadaveric organs and the availability of effective alternative minimally invasive procedures such as 900 Costa et al

Fig. 7. Survival curves for the DSRS and TIPS DIVERT Study patients. ( From Henderson JM. Surgery versus transjugular intrahepatic portal systemic shunt in the treatment of severe variceal bleeding. Clin Liver Dis 2006;10:610; with permission.)

endoscopic ablation and TIPS. Both procedures are sometimes complementary, with more use of the TIPS procedure in patients with gastric varices and those who are not amenable for endoscopic treatment. However, emergent surgical intervention may still play a significant role as a life-saving therapeutic modality, particularly in patients with failed TIPS and those with portomesenteric venous thrombosis or Budd-Chiari syndrome. When emergent surgical decompression is required for patients who are transplant candidates, an interposition mesocaval or mesorenal shunt, which can simply be ligated during the transplant operation, is recommended. The conventional total portosystemic shunts, particularly those who require hepatic hilar dissection, can precipitate liver failure and increase the operative risk at the time of surgery or transplantation. In the presence of adequate hepatic reserve and hemodynamic stability, emergent selective shunt can also be used with a high success rate. With

Fig. 8. Cavoportal hemitransposition with end-to-end ( A) or end-to-side ( B) anastomosis. Note plication of the inferior vena cava above the anastomosis with the end-to-side anastomosis. ( From Tzakis AG, Kirkegaard P, Pinna AD, et al. Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal vein thrombosis. Transplantation 1998;65:622; with permission.) Surgical Shunt Versus Tips 901 portomesenteric venous thrombosis, gastric devascularization with left gastric vein ligation is probably the only therapeutic option when medical treatment fails. Nonethe- less, all of these procedures are palliative measures and are commonly used as a bridge to transplantation. For elective therapy, the quantity of the functional hepatic reserve is the most important factor to be considered in the decision-making process and timing of transplantation. With Child C cirrhosis, liver transplantation seems to be the only therapeutic option for variceal bleeders. For compensated (Child A/B) cirrhotics with adequate hepatic reserve, a simmering controversy still exists regarding the issue of liver transplantation versus shunt procedures. In these patients, the choice between shunting and transplantation after failure of endoscopic intervention is often difficult. Although long-term survival for this group is probably superior with transplantation, a portal perfusion–preserving operation, preferably DSRS, may serve for several years as an effective bridge to transplantation. Because of its nonsurgical nature, TIPS has recently been promoted to treat patients with good hepatic reserve who may not require liver transplantation for a long time, as discussed earlier. With better understanding of transplant immunology and allograft tolerance with minimization or discontinuation of immunosuppression, liver transplantation may stand in the near future as the treatment of choice with normal life expectancy. The

Fig. 9. Total replacement of the splanchnic organs with a multivisceral allograft, including stomach, duodenum, pancreas, intestine, and liver. Note the en bloc total replacement of the thrombosed portomesenteric venous system with the transplanted organs. ( From Abu-Elmagd K, Costa G, Bond GJ, et al. Five hundred intestinal and multivisceral transplantations at a single center. Major advances with new challenges. Ann Surg 2009;250(4): 569; with permission.) 902 ot tal et Costa

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Fig. 10. The algorithmic management of acute and recurrent variceal hemorrhage. Surgical Shunt Versus Tips 903 problem of organ shortage has been recently ameliorated by the innovative techniques of cadaveric split and live-donor transplantation. Further evolution of the field has also been recently fueled by the growing knowledge of stem cell biology and gene technology, with the hope for organ engineering and xenotransplantation.

Multivisceral Transplantation With portomesenteric and splenic venous thrombosis, variceal bleeders with combined parenchymal and vascular decompensation have very limited therapeutic options. These options are commonly dictated by the extent of the thrombotic process and the pattern of collateral development. With isolated portal vein thrombosis, liver transplantation has been used with increasing frequency since the technique of portal throm- bectomy and venous jump graft was introduced at the authors’ institution during the late 1980s. 33 With extensive portomesenteric venous thrombosis, liver replacement with cavoportal hemitransposition ( Fig. 8 ) and multivisceral transplantation ( Fig. 9 ) are the only two technically feasible transplant procedures that could be offered to these patients. 34,35 The cavoportal hemitransposition technique was advocated at times when the multivisceral transplant procedure was technically challenging with a poor outcome. With the recent evolution of multivisceral transplantation and continuous improvement in survival, the procedure should be offered to all variceal bleeders with extensive portomesenteric and splenic vein thrombosis. 35 A major disadvantage of the cavoportal hemitransposition technique is the persistent risk of life-threatening variceal hemorrhage, because the procedure usually fails to decompress the thrombosed portomesenteric and splenic venous system. With multivisceral transplantation, the visceral collaterals as well as the gastrointestinal varices are eradicated by replacing the thrombosed portal venous system en bloc with the donor stomach, duodenum, pancreas, intestine, and liver.

SUMMARY The authors’ current policy for the management of variceal bleeders based on the status of the portomesenteric venous system and hepatic reserve is summarized in Fig. 10 . This new management algorithm requires a multidisciplinary team approach in a tertiary center with the availability of surgical and radiologic expertise in portal hypertension and abdominal organ transplantation. In brief, surgical shunt and TIPS are equally effective in the management of Child A/B variceal bleeders, and organ transplantation should be considered for patients with Child C cirrhosis and those who fail the shunt procedure or develop progressive liver failure.

ACKNOWLEDGMENTS The authors would like to thank Darlene Koritsky for her extraordinary efforts in preparing the manuscript.

REFERENCES 1. Lebrec D, Moreau R. Pathophysiology of portal hypertension. Hepatogastroenter- ology 1999;46:1426–8. 2. Boyer TD. Natural history of portal hypertension. Clin Liver Dis 1997;1:31–44. 3. Groszmann R. Hyperdynamic circulation of liver disease forty years later: pathophysiology and clinical consequences. Hepatology 1994;20:1359–63. 904 Costa et al

4. Pinzani M, Vizzutti F. Anatomy and vascular biology of the cells in the portal circulation. In: Sanyal AJ, Shah VH, editors. Clinical gastroenterology: portal hypertension. Totowa (NJ): Humana Press Inc; 2005. p. 15–35. 5. Rockey DC. Cell and molecular mechanisms of increased intrahepatic resistance and hemodynamic correlates. In: Sanyal AJ, Shah VH, editors. Clinical gastroenterology: portal hypertension. Totowa (NJ): Humana Press Inc; 2005. p. 37–50. 6. Wiest R, Grozsmann RJ. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology 2002;35:478–91. 7. Moreau R, Lebrec D. Molecular and structural basis of portal hypertension. Clin Liver Dis 2006;10:445–57. 8. Rana SS, Bhasin DK. Gastrointestinal bleeding: from conventional to nonconventional. Endoscopy 2008;40(1):40–4. 9. Garcia-Tsao G, Lim JK, Members of Veterans Affairs Hepatitis C Resource Center Program. Management and treatment of patients with cirrhosis and portal hypertension: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program. Am J Gastroen- terol 2009;104(7):1802–29. 10. Toubia N, Sanyal AR. Portal hypertension and variceal hemorrhage. Med Clin North Am 2008;92:551–74. 11. Sass DA, Chopra KB. Portal hypertension and variceal hemorrhage. Med Clin North Am 2009;93(4):837–53. 12. Kravetz D. Prevention of recurrent esophageal variceal hemorrhage: review and current recommendations. J Clin Gastroenterol 2007;41(3):S318–22. 13. Garcia-Pagan JC, De Gottardi A, Bosch J. Review article: the modern management of portal hypertension: primary and secondary prophylaxis of variceal bleeding in cirrhotic patients. Aliment Pharmacol Ther 2008;28(2):178–86. 14. de Franchis R, Dell’Era A, Primignani M. Diagnosis and monitoring of portal hypertension. Dig Liver Dis 2008;40(5):312–7. 15. Boyer TD, Henderson JM. Portal hypertension and bleeding esophageal varices. In: Zakim D, Boyer TD, editors. Hepatology: a textbook of liver disease. 4th edition. Philadelphia: WB Saunders; 2002. p. 581. 16. Stipa S, Balducci G, Ziparo V, et al. Total shunting and elective management of variceal bleeding. World J Surg 1994;18:200–4. 17. Orloff MJ, Orloff MS, Orloff SL, et al. Three decades of experience with emergency portocaval shunt for acutely bleeding esophageal varices in 400 unse- lected patients with cirrhosis of the liver. J Am Coll Surg 1995;180:257–72. 18. Collins JC, Ong J, Rypins EB, et al. Partial portacaval shunt for variceal hemorrhage. Longitudinal analysis of effectiveness. Arch Surg 1998;133:590–3. 19. Sarfeh IJ, Rypins EB, Mason GR. A systematic appraisal of portocaval H-graft diameters. Clinical and hemodynamics perspectives. Ann Surg 1986;204: 356–63. 20. Rosemurgy AS, Goode SE, Zwiebel BR, et al. A prospective trial of transjugular intrahepatic portosystemic stent shunt vs. small diameter prosthetic H-graft portacaval shunts in the treatment of bleeding varices. Ann Surg 1996;224:378–84. 21. Warren WD, Zeppa R, Fomon JJ. Selective trans-splenic decompression of gastroesophageal varices by distal splenorenal shunt. Ann Surg 1967;166: 437–55. 22. Henderson JM, Millikan WJ Jr, Warren WD. The distal splenorenal shunt: an update. World J Surg 1984;8:722–32. 23. Henderson JM, Millikan WJ Jr, Warren WD. Selective variceal decompression: current status and recent advances. Adv Surg 1984;18:81–116. Surgical Shunt Versus Tips 905

24. Maillard JN, Flamant YM, Hay JM, et al. Selectivity of the distal splenorenal shunt. Surgery 1979;86(5):663–71. 25. Warren WD, Millikan WJ, Henderson JM, et al. Splenopancreatic disconnection: improved selectivity of distal splenorenal shunt. Ann Surg 1986;204(4):346–55. 26. Henderson JM. Surgery versus transjugular intrahepatic portal systemic shunt in the treatment of severe variceal bleeding. Clin Liver Dis 2006;10:599–612. 27. Inokuchi K, Kobayashi M, Kusaba A, et al. New selective decompression of esophageal varices by a left gastric venous-caval shunt. Arch Surg 1970;100: 157–62. 28. Inokuchi K, Sugimachi K. The selective shunt for variceal bleeding: a personal perspective. Am J Surg 1990;160(1):48–53. 29. Rosemurgy AS, Bloomston M, Clark WC, et al. H-graft portacaval shunts vs. TIPS: ten year follow up of a randomized trial with comparison to predicted survivals. Ann Surg 2005;241:238–46. 30. Henderson JM, Boyer TD, Kutner MH, et al. Distal splenorenal shunt versus transjugular intrahepatic portal systematic shunt for variceal bleeding: a randomized trial. Gastroenterology 2006;130(6):1643–51. 31. Boyer TD, Henderson MJ, Heery AM, et al. Cost of preventing variceal rebleeding with transjugular intrahepatic portal systemic shunt and distal splenorenal shunt. J Hepatol 2008;48:407–14. 32. Iwatsuki S, Starzl TE. Liver transplantation in the management of bleeding esophageal varices. Baillieres Clin Gastroenterol 1992;6(3):517–25. 33. Tzakis AG, Todo S, Stieber A, et al. Venous jump grafts for liver transplantation in patients with portal vein thrombosis. Transplantation 1989;48:530–1. 34. Tzakis AG, Kirkegaard P, Pinna AD, et al. Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal vein thrombosis. Transplanta- tion 1998;65:619–24. 35. Abu-Elmagd KM, Costa G, Bond GJ, et al. Five hundred intestinal and multivisceral transplantations at a single center. Major advances with new challenges. Ann Surg 2009;250(4):567–81.