Beneficial Impact of Temporary Portocaval Shunt in Living-Donor Liver Transplantation With a Difficult Total Hepatectomy J.D. Kim and D.L. Choi* Division of Hepatobiliary Pancreas Surgery and Abdominal Organ Transplantation, Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, Korea

ABSTRACT Background. Although a temporary portocaval shunt (TPCS) improves hemodynamic stability during liver transplantation, the role of TPCS is controversial. We assessed the effects of TPCS in patients undergoing living-donor liver transplantation (LDLT) with a difficult total hepatectomy. Methods. We analyzed outcomes by means of retrospective review of 116 LDLTs performed in our institution from May 2011 to October 2013; among these, 33 recipients received TPCS (group I) and 83 did not (group II). We performed TPCS in a high-risk group, such as those with severe perihepatic adhesions, severe retrohepatic adhesions to the vena cava, or massive bleeding during total hepatectomy. Patient demographics and intraoperative and postoperative variables were reviewed. Results. No significant differences were observed in the perioperative variables except intraoperative blood loss. The transfusion requirement and operative time in group I were similar to those in group II despite the higher blood loss and more complicated cases. Hemodynamic status and the vasopressor requirement during the operation were similar between the 2 groups. We also compared 2 subgroups to evaluate the effects of TPCS more precisely in the high-risk patients: subgroup A (Model for End-Stage Liver Disease score [MELD], >20) and subgroup B (MELD, 20). The intraoperative requirements for platelet concentrate and epinephrine during the early reperfusion phase in subgroup A were significantly lower than those in subgroup A without TPCS. Conclusions. TPCS was a safe and useful procedure to improve hemodynamic status and postoperative LDLT outcomes in high-risk and select patients.

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HE TEMPORARY portocaval shunt (TPCS) technique was introduced by Ringe et al [1] for use in critically ill patients with fulminant hepatic failure and toxic liver syndrome, severe hepatic trauma, or primary nonfunction [1,2]. Clamping of the portal vein leads to interrupted venous return to the heart, congestion of the splanchnic bed, and intestinal edema, subsequently leading to hemodynamic instability, impaired renal function, and reperfusion syndrome [3e5]. Therefore, this technique enables many surgeons to perform liver transplantation (LT) with good results, if they maintain hemodynamic stability, reduce blood loss, preserve renal function, and reduce the incidence of reperfusion syndrome [4,6]. However, the role or routine use of TPCS in patients with cirrhosis remains controversial despite these benefits 0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.12.036

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[4,7,8]. Moreover, only a few reports have demonstrated technical or hemodynamic effects of a TPCS during livingdonor liver transplantation (LDLT), unlike the numerous TPCS reports available during deceased-donor liver transplantation (DDLT) [9]. The aim of the present study was to analyze hemodynamic parameters and to validate the usefulness of a TPCS in patients undergoing LDLT with a difficult total hepatectomy.

*Address correspondence to Dong Lak Choi, MD, Division of Hepatobiliary Pancreas Surgery and Abdominal Organ Transplantation, Department of Surgery, Catholic University of Daegu College of Medicine, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu, 705-718, Korea. E-mail: [email protected] ª 2015 Published by Elsevier Inc. 360 Park Avenue South, New York, NY 10010-1710

Transplantation Proceedings, 47, 694e699 (2015)

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Table 1. Intraoperative and Postoperative Outcomes Variable

Recipient Operation time (min) Estimated blood loss (mL) Cold ischemia time (min) Anhepatic phase time (min) Intraoperative transfusion requirement (mL) Packed red blood cells Platelet concentrates Fresh frozen plasma ICU stay (d) Postoperative hospital stay (d) In-hospital mortality [n (%)] Graft Fatty change (%) Graft type (MRL/ERL) GRWR

Group I (n ¼ 33)

448.4 2,268.2 110.1 167.1

   

Group II (n ¼ 83)

67.6 1,794.1 24.0 57.9

428.5 1,536.8 103.4 61.2

822.1  691.0 236.9  272.7 1,116.9  610.5 4.9  2.23 24.3  6.0 1 (3.0) 0.6  2.7 31/2 1.12  0.21

   

P Value

90.9 913.2 20.2 15.2

.257 .032 .125 .000

747.4  828.1 275.1  221.3 1160.9  632.3 4.7  2.4 24.1  7.3 4 (4.8)

.647 .436 .733 .256 .875 .669

2.4  6.2 74/9 1.15  0.22

.033 .428 .550

Abbreviations: ICU, intensive care unit; MRL, modified right lobe; ERL, extended right lobe; GRWR, graft-to-recipient weight ratio.

MATERIALS AND METHODS A total of 116 LDLTs with a right lobe graft were performed at Daegu Catholic University Medical Center, Daegu, Korea, from May 2011 to October 2013. The patients were divided into 2 groups, depending on TPCS use: those who received a TPCS (n ¼ 33; group I) and those who did not (n ¼ 83; group II). We do not routinely perform TPCS during LDLT. Instead, we perform TPCS in select cases, such as those with acute liver failure with toxic liver syndrome, severe perihepatic adhesions such as previous upper abdominal surgery, severe retrohepatic adhesions to the vena cava, large caudate lobes that lead to difficult retrohepatic dissection, and massive perihepatic bleeding during total hepatectomy requiring total hepatic inflow occlusion. Among these high-risk cases, we excluded acute liver failure from our study because we focused mainly on the technical aspects of a difficult total hepatectomy during LDLT. Medical records were reviewed retrospectively, and comparisons between the 2 groups were made for the patient demographic and intra- and postoperative findings, such as age, disease etiology, laboratory data, intraoperative outcomes, including hemodynamic changes, postoperative complications, and long-term outcomes. This study was approved by the Institutional Review Board of the Daegu Catholic University Medical Center.

Surgical Technique The LDLT surgical technique with the use of a right lobe graft including a total hepatectomy has been described previously [10,11]. The hilar structures were dissected before dissecting the retrohepatic vena cava from the liver in recipients undergoing LDLT with TPCS, whereas the conventional extrahepatic approach calls for hilar dissection after full perihepatic mobilization. The hepatic artery and bile duct were dissected and ligated, and the portal vein was dissected from the level of the pancreaticoduodenal vein to the bifurcation. After these structures were divided, a total hepatectomy with retrohepatic cava preservation and selective clamping of the hepatic veins was completed. After the total hepatectomy, the distal end of the portal vein was anastomosed end-to-side to the infrahepatic vena cava or end-to-end to the middle and left hepatic vein trunk, depending on the redundancy or length of the portal vein. In cases requiring prompt inflow control owing to massive

bleeding or severe fibrosis of the hilum, we used the mass clamping technique for the hilum instead of classic dissection of the hilar structures. The remaining perihepatic dissection was completed after the high hilar plate was dissected using a suction tip or scissors, and the hilar structures were transected as distally as possible. Then the portal vein was isolated from the surrounding structures, and the remaining hilar structures were dissected and clamped separately with the use of vascular clamps, as with the high hilar dissection [11]. The portal vein was ligated and cut just proximally to the portocaval suture to begin an end-to-end portal anastomosis once the hepatic vein anastomosis was completed. All of the hepatic arterial reconstruction was performed under a microscope, and biliary anastomosis usually featured duct-to-duct reconstruction with external biliary drainage. Intraoperative Doppler ultrasonography was used to assess graft patency in terms of inflow and outflow.

Statistical Analysis All numeric data are reported as means with standard deviations or as medians with ranges. Student t test or Mann-Whitney U test was used to compare continuous variables, depending on their distributions. The chi-square or Fisher exact test was applied to compare categoric variables after certain assumptions were verified. Survival rates of the recipients and grafts were determined using the KaplanMeier method and compared with the use of the log-rank test. All analyses were performed with the use of IBM SPSS Statistics v19.0 (IBM, Armonk, New York). A P value of 20) and subgroup B (MELD score, 20) to evaluate the effects of TPCS on LDLT according to the MELD score. The intraoperative platelet concentrate and epinephrine requirements during the early reperfusion phase in subgroup A with TPCS were significantly lower than those in patients who did not receive TPCS (Tables 3 and 4). However, no differences were observed in subgroup B. DISCUSSION

The use of TPCS was initially recommended for patients with fulminant hepatic failure due to a critical systemic inflammatory syndromeelike response called toxic liver syndrome [1,5,12]. Total portal vein clamping during the anhepatic phase leads to unstable hemodynamics and decreased venous return and cardiac output. At the same time, the increased pressure in the splanchnic system reflects the microcirculation, leading to increased membrane permeability, interstitial edema, endothelial damage, and consequent production of proinflammatory cytokines [3,6,13]. Release of these factors into the systemic circulation after declamping may lead to systemic vasodilatation, severe hypotension, and organ damage, referred to as reperfusion syndrome [6,14]. TPCS

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Table 3. Subgroups With High MELD Score (>20): Comparison of Perioperative Variables Variable

Intraoperative variables Operation time (min) Estimated Blood loss (mL) Intraoperative transfusion requirement (mL) Packed red blood cells Platelet concentrates Fresh frozen plasma Postoperative variables ICU stay (d) Postoperative hospital stay (d) In-hospital mortality [n (%)] Need for inotropics during immediate POD [n (%)] Postoperative bleeding [n (%)] Portal vein complication [n (%)] Hepatic artery complication [n (%)] Bile duct stricture [n (%)]

TPCS Group (n ¼ 11)

Non-TPCS Group (n ¼ 20)

P Value

463.1  0.9 2718.1  2437.5

411.8  85.3 1625.0  775.9

.180 .234

502.7  495.1 168.2  197.8 1010.9  458.4

1041.0  1103.0 321.0  206.1 1228.0  841.1

.120 .048 .751

5.7  3.3 24.0  6.4 1 (9.1) 2 (18.1)

6.4  4.5 28.4  3.3 3 (15.0) 4 (20.0)

.669 .321 1.000 1.000

3 (15.0) 1 (9.1) 1 (9.1) 1 (9.1)

2 (10.0) 4 (5.0) 0 (0.0) 0 (0.0)

.638 1.000 .355 1.000

Abbreviations: TPCS, temporary portocaval shunt; ICU, intensive care unit; POD, postoperative days.

prevents prolonged portal clamping and subsequent splanchnic congestion, thereby improving intraoperative hemodynamics and renal function and avoiding all effects caused by increased splanchnic pressure [3,4,6,8]. Even though TPCS is indisputably beneficial in cases of fulminant hepatic failure and subacute liver failure with portal hypertension, owing to better outcomes, the efficacy and hemodynamic benefit of TPCS have not been clearly demonstrated in patients with cirrhosis [1,8,15]. In fact, most studies have failed to show improved perioperative hemodynamics, renal function, or perioperative complications, because anatomic shunts decompress the splanchnic system [4,16]. Nevertheless, several studies have shown a decrease in hemodynamic disturbances and blood component requirements when TPCS is performed during LT in patients with cirrhosis [15]. Tzakis et al [5] and Belgiti et al [12] described that the use of TPCS combined with the piggyback technique results in better hemodynamic stability and improved renal function as

well as a decreased transfusion requirement. In addition, Margarit et al [17] and Figueras et al [18] demonstrated improved hemodynamic status, reduced intraoperative transfusion requirements, and better renal function during and after DDLT among patients who underwent TPCS. Furthermore, use of TPCS could facilitate an easier and safer total hepatectomy technically in addition to its beneficial effects [4,8,13]. First, dividing the recipient portal vein early leads to less bleeding during dissection and hepatectomy, translating often more difficult steps into a more straightforward procedure that is less time consuming [4,6]. Actually, only a few minutes are needed for a skilled surgeon to complete the TPCS. Thus, the operation time in the TPCS group was not longer than in the non-TPCS group, despite the more complex cases in the TPCS group. Second, improving operative exposure provides the opportunity to perform retrohepatic dissection under controlled

Table 4. Subgroups With High MELD Score (>20): Comparison of Systemic Hemodynamics Variable

Hemodynamics at AHP CI (L/min/m2) MAP (mm Hg) CVP (mm Hg) SVRI (dyne$s/cm5/m2) Need for NEPi injection [n (%)] Need for EPi injection [n (%)] Hemodynamics on REP CI (L/min/m2) MAP (mm Hg) CVP (mm Hg) SVRI (dyne$s/cm5/m2) Need for NEPi injection [n (%)] Need for EPi injection [n (%)] Abbreviations as in Tables 2 and 3.

TPCS Group (n ¼ 11)

Non-TPCS Group (n ¼ 20)

P Value

4.5  1.3 70.8  9.4 3.0  2.5 1,264.6  325.9 4 (36.4) 3 (27.3)

3.7  1.1 73.9  10.6 4.1  2.4 1,636.6  492.7 3 (15.0) 11 (55.0)

.061 .548 .189 .033 .210 .258

4.1  1.0 65.0  10.2 4.5  3.5 1,229.2  352.7 4 (36.4) 3 (27.3)

3.7  1.5 68.1  12.4 5.0  2.7 2,051.9  2892.1 3 (15.0) 14 (70.0)

.311 .679 .338 .248 .210 .031

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circumstances [4]. Therefore, TPCS allows an inexperienced surgeon to easily perform some difficult LT steps [4]. In fact, a fully devascularized liver and shorter final hemostasis could reduce the intraoperative red blood cell transfusion requirement in the TPCS group [6]. Third, the use of TPCS minimizes the effects of prolonged portal vein clamping, reducing the urgency to implant the liver [6]. The TPCS is disrupted for a portal anastomosis after a hepatic vein anastomosis is completed at our institution. Therefore, this actually reduces the necessity to rush during the anastomosis. Finally, a portal vein thrombosis allows more time to assess the effect of the thrombectomy while maintaining continuous flow through the portal vein, thereby avoiding eventual rethrombosis [8]. Similarly to other transplant centers, we introduced TPCS in patients with fulminant hepatic failure and toxic liver syndrome, and its technical feasibility and usefulness were so positive that we extended its application to difficult total hepatectomies. We do not use TPCS routinely during LDLT, as suggested by other authors [4,6]. Rather, we use TPCS selectively in patients with fulminant hepatic failure and certain high-risk conditions, such as previous upper abdominal surgery, retransplantation, severe perihepatic adhesions to the vena cava, large caudate lobe leading to a difficult retrohepatic dissection, and accidentally encountered massive perihepatic bleeding during total hepatectomy. In addition, we often decide to use TPCS during LDLT rather than preoperatively to overcome difficult steps or unexpected massive bleeding during a total hepatectomy. These observations explain why intraoperative blood loss was significantly greater in the TPCS than in the non-TPCS group, whereas several other studies reported that TPCS reduces intraoperative blood loss [2,4,6,13]. However, we found that the intraoperative transfusion and vasopressor requirements and hemodynamic status during the anhepatic and early reperfusion phase were similar between the 2 groups, despite the higher blood loss and more complex conditions, as in other studies demonstrating better outcomes [4,6,17,18]. Several studies have reported that dividing the recipient portal vein early facilitates total hepatectomy during LDLT substantially [11,19]. Mass clamping of the hilum or the high hilar dissection method was introduced to facilitate hilar dissection in cases of portal vein thrombosis, previous surgery, and radiation. In actuality, the hilar structures are virtually inseparable, and classic dissection can result in injury to the portal vein and excess bleeding. Despite the technical benefits, these methods result in an extended anhepatic phase and severe complications related to prolonged portal vein clamping [19]. Therefore, TPCS was applied to overcome the potential limitations of these methods. We use the mass clamping technique for the hilum [19] and subsequent TPCS instead of classic dissection of the hilar structures in cases requiring prompt inflow control owing to massive bleeding or a difficult hilar dissection. Renal impairment is a common sequel to liver transplantation. Impaired renal perfusion, vascular instability, and release of cytokines at the time of reperfusion reduce

KIM AND CHOI

portal flow and renal function [20]. Preserving portal flow with the use of TPCS is associated with a lower incidence of postoperative acute renal failure [5,12]. Similarly, creatinine values during the early post-transplantation period did not differ between our 2 groups, despite significantly higher preoperative creatinine levels and more intraoperative blood loss in the TPCS than non-TPCS group. Therefore, we suggest that TPCS has beneficial effects on renal function in patients undergoing LDLT. This study was not a randomized controlled trial, and several biases (ie, lack of policy regarding indications for the use of TPCS, except the surgeon’s patient-based personal decision) limit the conclusions. We divided the patients into 2 subgroups according to the MELD score to overcome these limitations, including selection biases. In the subgroup with a MELD score >20, TPCS reduced the intraoperative blood and vasopressor requirements during the early reperfusion phase, and these results may better support the beneficial effects of TPCS on hemodynamic stability and the transfusion requirement during LDLT, as in several DDLT studies [5,12,17,18]. In conclusion, TPCS was found to be a useful and important technique that contributed to improve hemodynamic status and postoperative outcomes for high-risk and select patients undergoing LDLT. However, a longer followup period and continued patient enrollment are needed to confirm the efficacy and safety of this procedure for LDLT. REFERENCES [1] Ringe B, Pichlmayr R, Lubbe N, Bornscheuer A, Kuse E. Total hepatectomy as temporary approach to acute hepatic or primary graft failure. Transplant Proc 1988;20:552e7. [2] Montalti R, Busani S, Masetti M, et al. Two-stage liver transplantation: an effective procedure in urgent conditions. Clin Transplant 2010;24:122e6. [3] Arzu GD, De Ruvo N, Montalti R, et al. Temporary portocaval shunt utility during orthotopic liver transplantation. Transplant Proc 2008;40:1937e40. [4] Davila D, Bartlett A, Heaton N. Temporary portocaval shunt in orthotopic liver transplantation: need for a standardized approach? Liver Transpl 2008;14:1414e9. [5] Tzakis AG, Reyes J, Nour B, Marino IR, Todo S, Starzl TE. Temporary end to side portacaval shunt in orthotopic hepatic transplantation in humans. Surg Gynecol Obstet 1993;176:180e2. [6] Ghinolfi D, Marti J, Rodriguez-Laiz G, et al. The beneficial impact of temporary porto-caval shunt in orthotopic liver transplantation: a single center analysis. Transpl Int 2011;24:243e50. [7] Audet M, Piardi T, Panaro F, et al. Four hundred and twentythree consecutive adults piggy-back liver transplantations with the three suprahepatic veins: was the portal systemic shunt required? J Gastroenterol Hepatol 2010;25:591e6. [8] de Cenarruzabeitia IL, Lazaro JL, Bilbao I, Balsells J. Portocaval shunt throughout anhepatic phase in orthotopic liver transplantation for cirrhotic patients. Transplant Proc 2007;39: 2280e4. [9] Sanchez-Cabus S, Fondevila C, Calatayud D, et al. Importance of the temporary portocaval shunt during adult living donor liver transplantation. Liver Transpl 2013;19:174e83. [10] Lee SG. Technique of reconstruction of hepatic veins in living-donor liver transplantation, especially for right hepatic vein and major short hepatic veins of right-lobe graft. J Hepatobiliary Surg 2006;13:131e8.

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[16] Suarez-Munoz MA, Santoyo J, Fernandez-Aguilar JL, et al. Transfusion requirements during liver transplantation: impact of a temporary portacaval shunt. Transplant Proc 2006;38:2486e7. [17] Margarit C, de Cenarruzabeitia IL, Lazaro JL, et al. Portacaval shunt and inferior vena cava preservation in orthotopic liver transplantation. Transplant Proc 2005;37:3896e8. [18] Figueras J, Llado L, Ramos E, et al. Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study. Liver Transpl 2001;7: 904e11. [19] Pararas N, Levi D, Selvaggi G, et al. Mass clamping of the hilum to facilitate difficult hepatectomy during liver transplantation: a single center 10 year experience. Ann Surg 2009;250: 273e6. [20] Belghiti J, Noun R, Sauvanet A, et al. Transplantation for fulminant and subfulminant hepatic failure with preservation of portal and caval flow. Br J Surg 1995;82:986e9.

Beneficial impact of temporary portocaval shunt in living-donor liver transplantation with a difficult total hepatectomy.

Although a temporary portocaval shunt (TPCS) improves hemodynamic stability during liver transplantation, the role of TPCS is controversial. We assess...
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