LIVER TRANSPLANTATION 21:914–921, 2015
ORIGINAL ARTICLE
Presentation, Diagnosis, and Management of Early Hepatic Venous Outflow Complications in Whole Cadaveric Liver Transplant Shirin Elizabeth Khorsandi, Anuja Athale, Hector Vilca-Melendez, Wayel Jassem, Andreas Prachalias, Parthi Srinivasan, Mohamed Rela, and Nigel Heaton Institute of Liver Studies, King’s College Hospital, London, United Kingdom
Early hepatic venous outflow obstruction (HVOO) can be a devastating complication leading to graft loss after liver transplantation (LT). A retrospective study on 777 adult LT recipients over a 5-year period (August 2007 to August 2012) was undertaken to determine the incidence of early HVOO presenting within 3 months of transplant, its clinical features and management, and potential technical risk factors related to the implanting technique. Cases of early HVOO were screened for by identifying recipients with problematic ascites within 3 months of transplant. Definitive diagnosis for HVOO was based on a wedge pressure of >12 mm Hg. Considering only whole livers, the incidence of early problematic ascites was 3% (20/ 695) of which more than one-third (35%, 7/20) were then confirmed to have HVOO. Overall, the incidence of early HVOO was 1% (7/695). Two hepatic veins (HVs) with extension piggybacks (PBs; n 5 423) were the dominant implanting technique in the time period of study rather than the 3 HV PB (n 5 182) and caval replacement techniques (n 5 82). Considering the implantation technique, all cases of HVOO occurred after 2 HVs when extension PBs had been used with an incidence of 1.7% (7/423). Institutionally, early HVOO was mainly managed surgically by either cavoplasty within a month of transplant (n 5 4) or retransplant (n 5 1), and the remainder (n 5 2) were medically managed with diuretics. In conclusion, early HVOO is rare, and there is no evidence from this study that a given implantation technique is at a higher risk of developing HVOO (2 HV with extension versus 3 HV and caval replacement; P 5 0.11). However, early revisional surgery for HVOO can preserve graft function with retransplantation being reserved for when surgical cavoplasty or radiological stenting is technically C 2015 AASLD. not possible. Liver Transpl 21:914-921, 2015. V Received February 10, 2015; accepted April 11, 2015. Conventional liver transplantation (LT) was first described with caval replacement.1 Drawbacks to this approach of implantation were the reduction in venous return, splanchnic bed congestion and low renal flow, which were addressed with the use of venovenous bypass. To preserve the retrohepatic cava and counter these problems, the piggyback (PB) LT was developed, where the donor suprahepatic cava was anastomosed to the recipient common orifice of 2 hepatic veins (HV), either the left and middle HV or
right and middle HV.2,3 The PB technique was further refined by the development of the 3 HV PB.4,5 Fundamental to the advantages gained from PB implantation are the temporary portocaval shunt (TPCS)6 and partial side clamping of the cava that minimize recipient hemodynamic disturbances and bowel congestion.7 Additional modifications to the classical PB LT implanting anastomosis were side-to-side,6 end-to-side cavocavostomy8 with additional consideration for the outflow anastomosis being required for living-related,
Abbreviations: AIH, autoimmune hepatitis; ALF, acute liver failure; CLD, chronic liver disease; CT, computed tomography; DBD, donation after brain death; DCD, donation after cardiac death; FHV, free hepatic vein; GRWR, graft-to-recipient weight ratio; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HV, hepatic vein; HVOO, hepatic venous outflow obstruction; ICB, intracerebral bleed; IVC, infrahepatic cava; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; NT, neurotrauma; PB, piggyback; PSC, primary sclerosing cholangitis; RA, right atrial; SAH, subarachnoid hemorrhage; TPCS, temporary portocaval shunt; VBDS, vanishing bile duct syndrome; VV, veno-veno. Potential conflict of interest: Nothing to report. Address reprint requests to Nigel Heaton, Institute of Liver Studies, King’s College Hospital, London SE5 9RS, United Kingdom. Telephone: 44 20 3299 4801; FAX: 44 20 3299 3575; E-mail: [email protected] DOI 10.1002/lt.24154 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2015 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 21, No. 7, 2015
split, reduced, and auxiliary grafts.9 In all implanting techniques, there are reported problems with hepatic venous outflow obstruction (HVOO)9-12 with the incidence increasing up to 15% in partial grafts.9,13 This article describes a 5-year single-institute experience of early HV outflow complications in adult cadaveric whole-graft recipients focusing on its presentation, diagnosis, technical risk factors, and management.
PATIENTS AND METHODS Patient Group: Identifying, Diagnosing, and Definition of Early HVOO A retrospective analysis of 777 consecutive LTs over a 5-year period (August 2007 to August 2012) at a single institution was undertaken. Pediatric recipients (12 mm Hg.18
Surgical Techniques Donation after brain death (DBD) and donation after cardiac death (DCD) livers were procured using standard techniques. Only controlled DCD livers were used (category 3 and 4) according to Maastricht classification19 and a modified Casavilla’s super-rapid technique was employed, with emphasis on rapid donor hepatectomy.20,21 Institutionally, the maximum accepted warm ischemia time (from oxygen saturations
KHORSANDI ET AL. 915
of 70% or systolic pressure of 50 mm Hg to aortic cannulation) was 30 minutes. The preservation solution was University of Wisconsin in all cases. Implanting techniques used during the period of study included both caval replacement and PB. In PB implantation, 3 HV, 2 HV with extension, side-to-side, and cavostomy/triangulation variants were used. In PB implantation, a TPCS was typically fashioned.3 Institutionally, veno-veno (VV) bypass is no longer routine but was used on a selective basis where the recipient was not tolerant of a trial cross clamp as reflected by mean arterial pressures of less than 60 mm Hg or if there was excessive bleeding during hepatectomy. In cases of domino transplant, institutional practice was to put the amyloid donor on VV bypass to facilitate hepatectomy en bloc with cava. The amyloid liver would then be implanted using the PB technique, and the amyloid donor would have caval implantation. Operative cavoplasty for HVOO involved Pringle of the hilus, clamping of the suprahepatic and infrahepatic cava. The caval anastomosis was then taken down, and the common orifice of the recipient HVs and donor cava were refashioned to facilitate triangulation of the anastomosis that was sutured with 4/0 Prolene. VV bypass facilities were available if needed.
Statistical Analysis Results are reported as mean 6 standard deviations or percentages. Continuous variables were compared using the Wilcoxon rank sum test and categorical variables were entered into contingency tables to be evaluated by the Pearson chi-square and Fisher’s exact test. Statistical significance was set at P < 0.05. Analysis was performed using SPSS, version 17 (IBM, Armonk, NY).
RESULTS Transplant Activity Over the 5-year period of study 777 adult transplants were done, of which 25 were living related, 49 right lobes, 2 left lobes, and 6 auxiliary. The remainder (n 5 695) received whole cadaveric livers of which DCD made up 24%, DBD made up 75%, and domino made up 1% of grafts used (see Table 1). Considering only recipients of whole livers, the average age was 55 6 2 years with an average Model for End-Stage Liver Disease (MELD) score of 14 6 2. Retransplantation made up 10% (n 5 69/695) of transplant activity. Chronic liver disease (CLD; 85%, n 5 592/695) was the main indication for transplant and acute liver failure (ALF; 15%, n 5 103/695) accounted for the remainder (see Table 1). In CLD, the leading reasons for transplant were alcohol-related liver disease (23%, n 5 136/592), hepatitis C virus (HCV; 17%, n 5 101/ 592), primary sclerosing cholangitis (PSC; 8%, n 5 50/592), primary biliary cirrhosis (8%, n 5 47/ 592), and hepatocellular carcinoma (HCC; 22%, n 5 131/592).
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TABLE 1. Summary of Recipient Demographics and Grafts Used Venous Implantation Technique Recipient and Liver Graft Characteristics Recipient age, years MELD CLD/ALF Redo LT DBD/DCD/Domino
Caval Replacement, n 5 82
3 HV PB, n 5 182
2 HV With Extension PB, n 5 423
44.9 6 14.9 14 6 6.3 73/9 20 68/14/0
51.4 6 21.1 14.7 6 5.9 156/26 11 132/46/4
50.2 6 13.5 15.3 6 6.7 355/68 38 312/105/6
NOTE: The total number of whole cadaveric LTs presented n 5 687, excluded from summary are PB variants of triangulation (0.5%, n 5 3) and side to side (0.8%, n 5 5) that are used only sporadically. Continuous data were presented as mean 6standard deviation. Implantation techniques summarized caval replacement, 3 HV PB, and 2 HV with extension PB. For each implantation technique, a breakdown of number of cases was done for ALF, CLD, redo LT, and MELD score. Also for each implantation technique, a summary was shown of donor livers numbers from domino recipient, DBD, and DCD.
TABLE 2. Summary of Recipient and Donor Clinical Characteristics Identified With Early HVOO After LT
Patient
Recipient Age,
Recipient
Graft
Donor Cause
Graft
Explant
Years
Sex
Disease
Weight, kg
Type
of Death
Weight, kg
Weight, kg
GRWR
1
27
Male
49
DBD
SAH
1.29
4.925
2.6
2 3 4 5 6 7
72 22 43 50 39 38
Female Male Male Male Male Female
Glycogen storage disease HCV HCC AIH VBDS HCV HCC PSC PSC
60 60 63 77 81 55
DCD DCD DBD DBD DBD DBD
SAH NT ICB ICB SAH ICB
1.41 1.69 0.79 1.94 1.33 1.25
1.48 2.56 2.33 1.61 2.29 Not done
2.4 2.8 1.25 2.5 1.6 2.2
Number
Figure 1. Postcontrast biphasic CT scan of abdomen demonstrating heterogenous enhancement of graft parenchyma, consistent with venous congestion. The major HVs are not visualized, and a large volume of ascites is present.
Implantation Techniques Table 1 summarizes the main implanting techniques used in the time period of study. PB was the
dominant approach for implantation in 88% of cases (n 5 613/695) over caval replacement (12%, n 5 82/ 695), and of the PB variant with 2 HVs with extensions was favored (69%, n 5 423/613), followed by 3
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KHORSANDI ET AL. 917
Figure 2. The cavogram demonstrates a displacement and extrinsic compression of the retrohepatic cava. The RA pressure is 6 mm Hg, the IVC pressure is 23 mm Hg, FHV pressure is 23 mm Hg, and wedge pressure is 39 mm Hg. Pressure measurements are consistent with HV outflow, with the level of obstruction being at the HV anastomosis with associated extrinsic compression of the retrohepatic cava.
approach was preferred (91%, 94/103) with caval replacement being used only occasionally (9%, 9/ 103). ALF recipients, where caval replacement was the favored implanting technique, was in the setting of acute Budd-Chiari (n 5 8) or an early retransplant for HVOO (n 5 1).
Early Ascites After Transplant
Figure 3. Hematoxylin-eosin stain of formalin fixed allograft core needle biopsy. Demonstrating characteristic features of venous outflow of centrilobular hepatocyte drop out, centrilobular ectasia of sinusoids, and centrilobular patchy acute hemorrhage.
HVs (29.7%, n 5 182/613) with triangulation (0.5%, n 5 3/613), and side to side (0.8%, n 5 5/613). VV bypass was used in 8% (n 5 55/695) of transplants over the time period studied, typically being used in the retransplants (31%, n 5 17/55), acute BuddChiari (15%, n 5 8/55), and familial amyloid polyneuropathy (18%, n 5 10/55). In ALF (n 5 103), a PB
Of the 695 recipients who received a whole liver, 3% (n 5 20/695) were identified with symptomatic ascites needing medical management and investigation in the first 3 months after transplant. The majority were still inpatients, 75% (n 5 15/20), presenting with either ongoing high drain losses (n 5 8) and/or abdominal distension (n 5 11), and 1 patient was associated with a pleural effusion. The readmissions with symptomatic ascites, 25% (n 5 5/20), typically occurred at a month after transplant with the presenting complaint of abdominal distension. After further investigation (CT, pressure studies, and biopsy), just more than one-third (35%) of these early cases of ascites were confirmed to have HVOO (n 5 7). The remaining diagnoses of early ascites after transplant were initial poor graft function (n 5 3), chylous fluid loss (n 5 2), no clear diagnosis (n 5 4), veno-occlusive disease (n 5 2), pancreatitis (n 5 1), and portal vein stenosis (n 5 1). These non-HVOO early cases of ascites were managed
2008
2010
2011
2011
2012
2012
2
3
4
5
6
7
HVOO
Ascites
Ascites
Ascites
Ascites
Ascites
Pleural effusion
Ascites, drain losses
Presentation
Diagnosis
29
46
82
25
16
18
30
Time, Days
NOTE: Patient numbers correlate with those in Table 2. *Intraoperative splenic pulp pressure.
2008
1
LT
Year
Numbers
Patient
Outpatient
Outpatient
Outpatient
Inpatient
Inpatient
Inpatient
Inpatient
Location
Ascites
Ascites
Ascites
Ascites
Ascites
Ascites
Ascites
Ultrasound
Ascites, narrowing at anastomoses
Ascites, narrowing at anastomoses
HVs not visualized, congested liver, ascites
HVs not visualized, congested liver, ascites
HVs not visualized, congested liver, ascites
HVs not visualized, congested liver, ascites
HVs not visualized, congested liver, ascites
CT
Liver
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Biopsy
20
15
39
Not done
12
23
33*
Mm Hg
Pressure,
Transjugular Wedge HV
TABLE 3. Summary of Early Clinical and Diagnostic Findings in Early HVOO and Management Strategy Used
Management Cavoplasty; Operative findings: congested liver, twisting at HV anastomoses Cavoplasty; Operative findings: congested liver, stenoses at HV anastomoses Cavoplasty; Operative findings: congested liver, stenoses, and twisting of HV anastomoses Cavoplasty; Operative findings: congested liver, stenoses, at HV anastomoses Re-LT; Operative findings: congested liver, stenoses at HV anastomoses, with a fibrous flap lined by endothelium Medical/Diuretics; Spironolactone 150 mg once daily Medical/Diuretics; frusemide 20 mg once daily, spironolactone 25 mg once daily
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Figure 5. CT demonstrating a patent caval stent and an occluded HV stent (no contrast within). There is associated heterogeneous enhancement of the liver.
Figure 4. Fluoroscopic-guided stent insertion. The right HV was catheterized, and a 10-mm by 6-cm stent was placed via a transjugular route. A 14-mm by 8-cm stent was deployed in the retrohepatic cava via the right femoral vein.
medically, and the portal vein stenosis was stented by interventional radiology.
Characteristics and Management of Early HVOO Seven cases of early HVOO were identified; these cases were dispersed throughout the 5-year period of study (Table 2 summarizes recipient and donor clinical characteristics). Overall, the incidence of early HVOO was 1% (7/695) with diagnosis being confirmed at 35 6 23 days after transplant based on CT, pressure studies, and biopsy. Of these, graft function was normal in 1 with the remaining cases having mild cholestasis at the time of diagnosis. All had preserved renal function before commencement of diuretics (estimated glomerular filtration rate > 60). Typical CT findings for the diagnosis of HVOO were a heterogeneous liver with nonvisualization of HVs and normal inflow vasculature (see Fig. 1). The average wedge pressure was 22 6 10.5 mm Hg (see Fig. 2 for illustrative case) and characteristic histology findings were perivenular cell drop out and hemorrhagic congestion (see Fig. 3). Considering implantation technique, the cases of early HVOO that were identified occurred when 2 HVs with extension PB had been used, giving an incidence of 1.6% (7/423) for that technique. Statistically, with the present study design and numbers for each
implanting technique, it cannot be demonstrated that 2 HVs with extension gives a higher risk of early HVOO (P 5 0.114). In just under one-third of HVOO cases (29%, n 5 2/7) medical management with diuretics was successful with the remainder requiring surgical management (71%, n 5 5/7). Operative cavoplasty was successful in 80% of cases (n 5 4/5). The HVOO cases that were successfully managed by cavoplasty were all inpatients and revision was within a month of transplant (see Table 3 for summary of HVOO clinical, diagnostic findings, and management strategy). The 1 patient for whom cavoplasty was unsuccessful was readmitted 6 weeks after transplant presenting with tense ascites and diuretic-related renal dysfunction. The indication for transplant was HCC on a background of HCV. There was no underlying procoagulant disorder identified in the recipient and the cause of death in the donor was an intracerebral bleed. Figures 1 and 2 show the CT and pressure studies that supported the diagnosis of HVOO. A right lobe transjugular biopsy at the time of the pressure studies also corroborated the radiological and clinical diagnosis of HVOO. Histologically the findings were of centrilobular patchy acute hemorrhage with centrilobular necrosis. There was no associated thrombosis, rejection, or steatosis (see Fig. 3). Exploratory laparotomy for cavoplasty was decided upon, but at the time of the operation, the finding of severe portal hypertension combined with a large, congested liver led to the procedure being abandoned. Interventional radiology then deployed stents in the cava and HV in an attempt to relieve HVOO (see Fig. 4). After 3 days, the stents thrombosed despite anticoagulation (see Fig. 5). The patient was relisted and successfully retransplanted a week later. The implanting technique was caval replacement on VV bypass.
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DISCUSSION PB transplant evolved to counter the physiological problems of caval replacement, but concerns remain that the advantages gained are negated by a higher incidence of HVOO. In the literature, the reported incidence of HVOO is < 2% for caval replacement,9,10 3% to 4% for PB,11,12 with the incidence increasing up to 5% to 15% in pediatric recipients and partial grafts.13 Considering the PB variants, the incidence of HVOO ranges from 2.4% to 6.4% for standard PB and 1.8% to 5.5% for side to side, with advocates of the 3 HV technique reporting 1%.11,12,22 In the present report, the overall incidence of early HVOO was low at 1%, making it a rare complication, classically, presenting at a month after transplant with progressive ascites and minimal derangement in graft biochemistry. In previous published series, there are typically 4 phases of HVOO described: (1) immediate graft congestion on reperfusion, requiring the anastomosis to be refashioned or the right diaphragm to be plicated to adjust for the mismatch between a small graft and hepatic bed11,14; (2) acute Budd-Chiari presenting with graft dysfunction and ascites within 48 hours generally requiring retransplant as the HVs have thrombosed; (3) ascites within 3 months that typically is managed with diuretics; and (4) chronic through a combination of intimal hyperplasia/fibrosis that is increasingly managed by interventional radiology before retransplant is considered.11,22 In the present study, there are a number of limitations. First, it is retrospective, not randomized and driven by institutional preference. Additionally, the early cases of HVOO for this study were identified by the presenting complaint of problematic ascites, which will have missed cases of HVOO that were identified intraoperatively with congestion on reperfusion and immediately amended surgically, either by re-fashioning the anastomosis or plicating the diaphragm. The other subset of early HVOO that would not of been captured in the present study design is the case of transient ascites that reflects a compromise to right HV outflow, which occurs in the 3 HV PB; in that case, the liver remodels to produce right lobe atrophy. When medical management for HVOO fails, there are a number of endovascular options in the form of angioplasty or stents. However, most experience on stenting for HVOO is from partial rather than whole grafts,13,23 and there is a reluctance to use this strategy early or in the presence of thrombosis because of the potential risk of anastomotic rupture.22,24 Another consideration is that stents can migrate, and if deployment is not carefully planned, they may compromise retransplant or cavoplasty.13,14 A number of different surgical strategies have been used to resolve HVOO such as termino-terminal rescue cavocavostomy,25 renosplenic shunt,26 cavoatrial shunt27 and side-to-side stapled cavocavostomy.28 Ultimately, if HVOO rescue strategies are unsuccessful, retransplant is then required.
LIVER TRANSPLANTATION, July 2015
In conclusion, early HVOO can be a graft-losing complication that highlights the technical vulnerabilities of the alternative implanting techniques. This study illustrates that early HVOO is rare, and there is no evidence from this study, as it is not sufficiently powered, that a given implantation technique is more vulnerable to developing early HVOO. However, early revisional surgery for HVOO can preserve graft function with retransplantation being reserved for cases where surgical cavoplasty or radiological stenting is technically not possible.
REFERENCES 1. Starzl TE, Marchioro TL, Vonkaulla KN, Hermann G, Brittain RS, Waddell WR. Homotransplantation of the liver in humans. Surg Gynecol Obstet 1963;117:659-676. 2. Calne RY, Williams R. Liver transplantation in man. I. Observations on technique and organization in five cases. Br Med J 1968;4:535-540. 3. Tzakis A, Todo S, Starzl TE. Orthotopic liver transplantation with preservation of the inferior vena cava. Ann Surg 1989;210:649-652. 4. L azaro JL, Charco R, Revhaug A, Murio E, Balsells J, Hidalgo E, et al. Hemodynamics in human liver transplantation with inferior vena cava preservation. Transplant Proc 1997;29:2851-2852. 5. Cescon M, Grazi GL, Varotti G, Ravaioli M, Ercolani G, Gardini A, Cavallari A. Venous outflow reconstructions with the piggyback technique in liver transplantation: a single-center experience of 431 cases. Transpl Int 2005; 18:318-325. 6. Belghiti J, Panis Y, Sauvanet A, Gayet B, F ek et e F. A new technique of side to side caval anastomosis during orthotopic hepatic transplantation without inferior caval occlusion. Surg Gynecol Obstet 1992;175:270-272. 7. Figueras J, Llado L, Ramos E, Jaurrieta E, Rafecas A, Fabregat J, et al. Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study. Liver Transpl 2001;7:904-911. 8. Cherqui D, Lauzet JY, Rotman N, Duvoux C, Dhumeaux D, Julien M, Fagniez PL, et al. Orthotopic liver transplantation with preservation of the caval and portal flows. Technique and results in 62 cases. Transplantation 1994;58:793-796. 9. Settmacher U, N€ ussler NC, Glanemann M, Haase R, Heise M, Bechstein WO, Neuhaus P. Venous complications after orthotopic liver transplantation. Clin Transplant 2000;14:235-241. 10. Lerut J, Tzakis AG, Bron K, Gordon RD, Iwatsuki S, Esquivel CO, et al. Complications of venous reconstruction in human orthotopic liver transplantation. Ann Surg 1987;205:404-414. 11. Parrilla P, S anchez-Bueno F, Figueras J, Jaurrieta E, Mir J, Margarit C, et al. Analysis of the complications of the piggy-back technique in 1,112 liver transplants. Transplantation 1999;67:1214-1217. 12. Navarro F, Le Moine MC, Fabre JM, Belghiti J, Cherqui D, Adam R, et al. Specific vascular complications of orthotopic liver transplantation with preservation of the retrohepatic vena cava: review of 1361 cases. Transplantation 1999;68:646-650. 13. Ko GY, Sung KB, Yoon HK, Kim KR, Kim JH, Gwon DI, Lee SG, et al. Early posttransplant hepatic venous outflow obstruction: long-term efficacy of primary stent placement. Liver Transpl 2008;14:1505-1511. 14. Darcy MD. Management of venous outflow complications after liver transplantation. Tech Vasc Interv Radiol 2007; 10:240-245.
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15. John TG, Plevris JN, Redhead DN, Garden OJ, Finlayson ND, Sanfey HA. Massive ascitic fluid loss after liver transplantation. Gastroenterology 1996;111:564-565. 16. Nishida S, Gaynor JJ, Nakamura N, Butt F, Illanes HG, Kadono J, et al. Refractory ascites after liver transplantation: an analysis of 1058 liver transplant patients at a single center. Am J Transplant 2006;6:140-149. 17. Borsa JJ, Daly CP, Fontaine AB, Patel NH, Althaus SJ, Hoffer EK, et al. Treatment of inferior vena cava anastomotic stenosis with the Wallstent endoprosthesis after orthotopic liver transplantation. J Vasc Interv Radiol 1999;10:17-22. 18. Cirera I, Navasa M, Rimola A, Garcıa-Pag an JC, Grande L, Garcia-Valdecasas JC, et al. Ascites after liver transplantation. Liver Transpl 2000;6:157-162. 19. Kootstra G. Statement on non-heart-beating donor programs. Transplant Proc 1995;27:2965. 20. Muiesan P, Girlanda R, Jassem W, Melendez HV, O’Grady J, Bowles M, et al. Single-center experience with liver transplantation from controlled non-heartbeating donors: a viable source of grafts. Ann Surg 2005;242: 732-738. 21. Casavilla A, Ramirez C, Shapiro R, Nghiem D, Miracle K, Fung JJ, Starzl TE. Experience with liver and kidney allografts from non-heart-beating donors. Transplant Proc 1995;27:2898. 22. Wang SL, Sze DY, Busque S, Razavi MK, Kee ST, Frisoli JK, Dake MD. Treatment of hepatic venous outflow
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23.
24.
25.
26.
27.
28.
obstruction after piggyback liver transplantation. Radiology 2005;236:352-359. Buell JF, Funaki B, Cronin DC, Yoshida A, Perlman MK, Lorenz J, et al. Long-term venous complications after full-size and segmental pediatric liver transplantation. Ann Surg 2002;236:658-666. Weeks SM, Gerber DA, Jaques PF, Sandhu J, Johnson MW, Fair JH, Mauro MA. Primary Gianturco stent placement for inferior vena cava abnormalities following liver transplantation. J Vasc Interv Radiol 2000;11(part 1):177-187. Zamboni F, Sampietro R. Conversion to termino-terminal cavo-cavostomy as a rescue technique for infrahepatic obstruction after piggyback liver transplantation. Transpl Int 2008;21:1008-1010. Mazzaferro V, Regalia E, Pulvirenti A, Baratti D, Montagnino G, Bozzetti F. Renal-splenic shunt for infrahepatic occlusion after piggy-back liver transplantation. Transpl Int 1997;10:392-394. Eid A, Rahamimov R, Ilan Y, Tur-Kaspa R, Berlatzky Y. Cavoatrial shunt: a graft salvage procedure for suprahepatic caval anastomosis obstruction after liver transplantation. Liver Transpl Surg 1998;4:239-240. Quintini C, Miller CM, Hashimoto K, Philip D, Uso TD, Aucejo F, et al. Side-to-side cavocavostomy with an endovascular stapler: rescue technique for severe hepatic vein and/or inferior vena cava outflow obstruction after liver transplantation using the piggyback technique. Liver Transpl 2009;15:49-53.
ORIGINAL ARTICLE
Presentation, Diagnosis, and Management of Early Hepatic Venous Outflow Complications in Whole Cadaveric Liver Transplant Shirin Elizabeth Khorsandi, Anuja Athale, Hector Vilca-Melendez, Wayel Jassem, Andreas Prachalias, Parthi Srinivasan, Mohamed Rela, and Nigel Heaton Institute of Liver Studies, King’s College Hospital, London, United Kingdom
Early hepatic venous outflow obstruction (HVOO) can be a devastating complication leading to graft loss after liver transplantation (LT). A retrospective study on 777 adult LT recipients over a 5-year period (August 2007 to August 2012) was undertaken to determine the incidence of early HVOO presenting within 3 months of transplant, its clinical features and management, and potential technical risk factors related to the implanting technique. Cases of early HVOO were screened for by identifying recipients with problematic ascites within 3 months of transplant. Definitive diagnosis for HVOO was based on a wedge pressure of >12 mm Hg. Considering only whole livers, the incidence of early problematic ascites was 3% (20/ 695) of which more than one-third (35%, 7/20) were then confirmed to have HVOO. Overall, the incidence of early HVOO was 1% (7/695). Two hepatic veins (HVs) with extension piggybacks (PBs; n 5 423) were the dominant implanting technique in the time period of study rather than the 3 HV PB (n 5 182) and caval replacement techniques (n 5 82). Considering the implantation technique, all cases of HVOO occurred after 2 HVs when extension PBs had been used with an incidence of 1.7% (7/423). Institutionally, early HVOO was mainly managed surgically by either cavoplasty within a month of transplant (n 5 4) or retransplant (n 5 1), and the remainder (n 5 2) were medically managed with diuretics. In conclusion, early HVOO is rare, and there is no evidence from this study that a given implantation technique is at a higher risk of developing HVOO (2 HV with extension versus 3 HV and caval replacement; P 5 0.11). However, early revisional surgery for HVOO can preserve graft function with retransplantation being reserved for when surgical cavoplasty or radiological stenting is technically C 2015 AASLD. not possible. Liver Transpl 21:914-921, 2015. V Received February 10, 2015; accepted April 11, 2015. Conventional liver transplantation (LT) was first described with caval replacement.1 Drawbacks to this approach of implantation were the reduction in venous return, splanchnic bed congestion and low renal flow, which were addressed with the use of venovenous bypass. To preserve the retrohepatic cava and counter these problems, the piggyback (PB) LT was developed, where the donor suprahepatic cava was anastomosed to the recipient common orifice of 2 hepatic veins (HV), either the left and middle HV or
right and middle HV.2,3 The PB technique was further refined by the development of the 3 HV PB.4,5 Fundamental to the advantages gained from PB implantation are the temporary portocaval shunt (TPCS)6 and partial side clamping of the cava that minimize recipient hemodynamic disturbances and bowel congestion.7 Additional modifications to the classical PB LT implanting anastomosis were side-to-side,6 end-to-side cavocavostomy8 with additional consideration for the outflow anastomosis being required for living-related,
Abbreviations: AIH, autoimmune hepatitis; ALF, acute liver failure; CLD, chronic liver disease; CT, computed tomography; DBD, donation after brain death; DCD, donation after cardiac death; FHV, free hepatic vein; GRWR, graft-to-recipient weight ratio; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HV, hepatic vein; HVOO, hepatic venous outflow obstruction; ICB, intracerebral bleed; IVC, infrahepatic cava; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; NT, neurotrauma; PB, piggyback; PSC, primary sclerosing cholangitis; RA, right atrial; SAH, subarachnoid hemorrhage; TPCS, temporary portocaval shunt; VBDS, vanishing bile duct syndrome; VV, veno-veno. Potential conflict of interest: Nothing to report. Address reprint requests to Nigel Heaton, Institute of Liver Studies, King’s College Hospital, London SE5 9RS, United Kingdom. Telephone: 44 20 3299 4801; FAX: 44 20 3299 3575; E-mail: [email protected] DOI 10.1002/lt.24154 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2015 American Association for the Study of Liver Diseases. V
LIVER TRANSPLANTATION, Vol. 21, No. 7, 2015
split, reduced, and auxiliary grafts.9 In all implanting techniques, there are reported problems with hepatic venous outflow obstruction (HVOO)9-12 with the incidence increasing up to 15% in partial grafts.9,13 This article describes a 5-year single-institute experience of early HV outflow complications in adult cadaveric whole-graft recipients focusing on its presentation, diagnosis, technical risk factors, and management.
PATIENTS AND METHODS Patient Group: Identifying, Diagnosing, and Definition of Early HVOO A retrospective analysis of 777 consecutive LTs over a 5-year period (August 2007 to August 2012) at a single institution was undertaken. Pediatric recipients (12 mm Hg.18
Surgical Techniques Donation after brain death (DBD) and donation after cardiac death (DCD) livers were procured using standard techniques. Only controlled DCD livers were used (category 3 and 4) according to Maastricht classification19 and a modified Casavilla’s super-rapid technique was employed, with emphasis on rapid donor hepatectomy.20,21 Institutionally, the maximum accepted warm ischemia time (from oxygen saturations
KHORSANDI ET AL. 915
of 70% or systolic pressure of 50 mm Hg to aortic cannulation) was 30 minutes. The preservation solution was University of Wisconsin in all cases. Implanting techniques used during the period of study included both caval replacement and PB. In PB implantation, 3 HV, 2 HV with extension, side-to-side, and cavostomy/triangulation variants were used. In PB implantation, a TPCS was typically fashioned.3 Institutionally, veno-veno (VV) bypass is no longer routine but was used on a selective basis where the recipient was not tolerant of a trial cross clamp as reflected by mean arterial pressures of less than 60 mm Hg or if there was excessive bleeding during hepatectomy. In cases of domino transplant, institutional practice was to put the amyloid donor on VV bypass to facilitate hepatectomy en bloc with cava. The amyloid liver would then be implanted using the PB technique, and the amyloid donor would have caval implantation. Operative cavoplasty for HVOO involved Pringle of the hilus, clamping of the suprahepatic and infrahepatic cava. The caval anastomosis was then taken down, and the common orifice of the recipient HVs and donor cava were refashioned to facilitate triangulation of the anastomosis that was sutured with 4/0 Prolene. VV bypass facilities were available if needed.
Statistical Analysis Results are reported as mean 6 standard deviations or percentages. Continuous variables were compared using the Wilcoxon rank sum test and categorical variables were entered into contingency tables to be evaluated by the Pearson chi-square and Fisher’s exact test. Statistical significance was set at P < 0.05. Analysis was performed using SPSS, version 17 (IBM, Armonk, NY).
RESULTS Transplant Activity Over the 5-year period of study 777 adult transplants were done, of which 25 were living related, 49 right lobes, 2 left lobes, and 6 auxiliary. The remainder (n 5 695) received whole cadaveric livers of which DCD made up 24%, DBD made up 75%, and domino made up 1% of grafts used (see Table 1). Considering only recipients of whole livers, the average age was 55 6 2 years with an average Model for End-Stage Liver Disease (MELD) score of 14 6 2. Retransplantation made up 10% (n 5 69/695) of transplant activity. Chronic liver disease (CLD; 85%, n 5 592/695) was the main indication for transplant and acute liver failure (ALF; 15%, n 5 103/695) accounted for the remainder (see Table 1). In CLD, the leading reasons for transplant were alcohol-related liver disease (23%, n 5 136/592), hepatitis C virus (HCV; 17%, n 5 101/ 592), primary sclerosing cholangitis (PSC; 8%, n 5 50/592), primary biliary cirrhosis (8%, n 5 47/ 592), and hepatocellular carcinoma (HCC; 22%, n 5 131/592).
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TABLE 1. Summary of Recipient Demographics and Grafts Used Venous Implantation Technique Recipient and Liver Graft Characteristics Recipient age, years MELD CLD/ALF Redo LT DBD/DCD/Domino
Caval Replacement, n 5 82
3 HV PB, n 5 182
2 HV With Extension PB, n 5 423
44.9 6 14.9 14 6 6.3 73/9 20 68/14/0
51.4 6 21.1 14.7 6 5.9 156/26 11 132/46/4
50.2 6 13.5 15.3 6 6.7 355/68 38 312/105/6
NOTE: The total number of whole cadaveric LTs presented n 5 687, excluded from summary are PB variants of triangulation (0.5%, n 5 3) and side to side (0.8%, n 5 5) that are used only sporadically. Continuous data were presented as mean 6standard deviation. Implantation techniques summarized caval replacement, 3 HV PB, and 2 HV with extension PB. For each implantation technique, a breakdown of number of cases was done for ALF, CLD, redo LT, and MELD score. Also for each implantation technique, a summary was shown of donor livers numbers from domino recipient, DBD, and DCD.
TABLE 2. Summary of Recipient and Donor Clinical Characteristics Identified With Early HVOO After LT
Patient
Recipient Age,
Recipient
Graft
Donor Cause
Graft
Explant
Years
Sex
Disease
Weight, kg
Type
of Death
Weight, kg
Weight, kg
GRWR
1
27
Male
49
DBD
SAH
1.29
4.925
2.6
2 3 4 5 6 7
72 22 43 50 39 38
Female Male Male Male Male Female
Glycogen storage disease HCV HCC AIH VBDS HCV HCC PSC PSC
60 60 63 77 81 55
DCD DCD DBD DBD DBD DBD
SAH NT ICB ICB SAH ICB
1.41 1.69 0.79 1.94 1.33 1.25
1.48 2.56 2.33 1.61 2.29 Not done
2.4 2.8 1.25 2.5 1.6 2.2
Number
Figure 1. Postcontrast biphasic CT scan of abdomen demonstrating heterogenous enhancement of graft parenchyma, consistent with venous congestion. The major HVs are not visualized, and a large volume of ascites is present.
Implantation Techniques Table 1 summarizes the main implanting techniques used in the time period of study. PB was the
dominant approach for implantation in 88% of cases (n 5 613/695) over caval replacement (12%, n 5 82/ 695), and of the PB variant with 2 HVs with extensions was favored (69%, n 5 423/613), followed by 3
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KHORSANDI ET AL. 917
Figure 2. The cavogram demonstrates a displacement and extrinsic compression of the retrohepatic cava. The RA pressure is 6 mm Hg, the IVC pressure is 23 mm Hg, FHV pressure is 23 mm Hg, and wedge pressure is 39 mm Hg. Pressure measurements are consistent with HV outflow, with the level of obstruction being at the HV anastomosis with associated extrinsic compression of the retrohepatic cava.
approach was preferred (91%, 94/103) with caval replacement being used only occasionally (9%, 9/ 103). ALF recipients, where caval replacement was the favored implanting technique, was in the setting of acute Budd-Chiari (n 5 8) or an early retransplant for HVOO (n 5 1).
Early Ascites After Transplant
Figure 3. Hematoxylin-eosin stain of formalin fixed allograft core needle biopsy. Demonstrating characteristic features of venous outflow of centrilobular hepatocyte drop out, centrilobular ectasia of sinusoids, and centrilobular patchy acute hemorrhage.
HVs (29.7%, n 5 182/613) with triangulation (0.5%, n 5 3/613), and side to side (0.8%, n 5 5/613). VV bypass was used in 8% (n 5 55/695) of transplants over the time period studied, typically being used in the retransplants (31%, n 5 17/55), acute BuddChiari (15%, n 5 8/55), and familial amyloid polyneuropathy (18%, n 5 10/55). In ALF (n 5 103), a PB
Of the 695 recipients who received a whole liver, 3% (n 5 20/695) were identified with symptomatic ascites needing medical management and investigation in the first 3 months after transplant. The majority were still inpatients, 75% (n 5 15/20), presenting with either ongoing high drain losses (n 5 8) and/or abdominal distension (n 5 11), and 1 patient was associated with a pleural effusion. The readmissions with symptomatic ascites, 25% (n 5 5/20), typically occurred at a month after transplant with the presenting complaint of abdominal distension. After further investigation (CT, pressure studies, and biopsy), just more than one-third (35%) of these early cases of ascites were confirmed to have HVOO (n 5 7). The remaining diagnoses of early ascites after transplant were initial poor graft function (n 5 3), chylous fluid loss (n 5 2), no clear diagnosis (n 5 4), veno-occlusive disease (n 5 2), pancreatitis (n 5 1), and portal vein stenosis (n 5 1). These non-HVOO early cases of ascites were managed
2008
2010
2011
2011
2012
2012
2
3
4
5
6
7
HVOO
Ascites
Ascites
Ascites
Ascites
Ascites
Pleural effusion
Ascites, drain losses
Presentation
Diagnosis
29
46
82
25
16
18
30
Time, Days
NOTE: Patient numbers correlate with those in Table 2. *Intraoperative splenic pulp pressure.
2008
1
LT
Year
Numbers
Patient
Outpatient
Outpatient
Outpatient
Inpatient
Inpatient
Inpatient
Inpatient
Location
Ascites
Ascites
Ascites
Ascites
Ascites
Ascites
Ascites
Ultrasound
Ascites, narrowing at anastomoses
Ascites, narrowing at anastomoses
HVs not visualized, congested liver, ascites
HVs not visualized, congested liver, ascites
HVs not visualized, congested liver, ascites
HVs not visualized, congested liver, ascites
HVs not visualized, congested liver, ascites
CT
Liver
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Biopsy
20
15
39
Not done
12
23
33*
Mm Hg
Pressure,
Transjugular Wedge HV
TABLE 3. Summary of Early Clinical and Diagnostic Findings in Early HVOO and Management Strategy Used
Management Cavoplasty; Operative findings: congested liver, twisting at HV anastomoses Cavoplasty; Operative findings: congested liver, stenoses at HV anastomoses Cavoplasty; Operative findings: congested liver, stenoses, and twisting of HV anastomoses Cavoplasty; Operative findings: congested liver, stenoses, at HV anastomoses Re-LT; Operative findings: congested liver, stenoses at HV anastomoses, with a fibrous flap lined by endothelium Medical/Diuretics; Spironolactone 150 mg once daily Medical/Diuretics; frusemide 20 mg once daily, spironolactone 25 mg once daily
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KHORSANDI ET AL. 919
Figure 5. CT demonstrating a patent caval stent and an occluded HV stent (no contrast within). There is associated heterogeneous enhancement of the liver.
Figure 4. Fluoroscopic-guided stent insertion. The right HV was catheterized, and a 10-mm by 6-cm stent was placed via a transjugular route. A 14-mm by 8-cm stent was deployed in the retrohepatic cava via the right femoral vein.
medically, and the portal vein stenosis was stented by interventional radiology.
Characteristics and Management of Early HVOO Seven cases of early HVOO were identified; these cases were dispersed throughout the 5-year period of study (Table 2 summarizes recipient and donor clinical characteristics). Overall, the incidence of early HVOO was 1% (7/695) with diagnosis being confirmed at 35 6 23 days after transplant based on CT, pressure studies, and biopsy. Of these, graft function was normal in 1 with the remaining cases having mild cholestasis at the time of diagnosis. All had preserved renal function before commencement of diuretics (estimated glomerular filtration rate > 60). Typical CT findings for the diagnosis of HVOO were a heterogeneous liver with nonvisualization of HVs and normal inflow vasculature (see Fig. 1). The average wedge pressure was 22 6 10.5 mm Hg (see Fig. 2 for illustrative case) and characteristic histology findings were perivenular cell drop out and hemorrhagic congestion (see Fig. 3). Considering implantation technique, the cases of early HVOO that were identified occurred when 2 HVs with extension PB had been used, giving an incidence of 1.6% (7/423) for that technique. Statistically, with the present study design and numbers for each
implanting technique, it cannot be demonstrated that 2 HVs with extension gives a higher risk of early HVOO (P 5 0.114). In just under one-third of HVOO cases (29%, n 5 2/7) medical management with diuretics was successful with the remainder requiring surgical management (71%, n 5 5/7). Operative cavoplasty was successful in 80% of cases (n 5 4/5). The HVOO cases that were successfully managed by cavoplasty were all inpatients and revision was within a month of transplant (see Table 3 for summary of HVOO clinical, diagnostic findings, and management strategy). The 1 patient for whom cavoplasty was unsuccessful was readmitted 6 weeks after transplant presenting with tense ascites and diuretic-related renal dysfunction. The indication for transplant was HCC on a background of HCV. There was no underlying procoagulant disorder identified in the recipient and the cause of death in the donor was an intracerebral bleed. Figures 1 and 2 show the CT and pressure studies that supported the diagnosis of HVOO. A right lobe transjugular biopsy at the time of the pressure studies also corroborated the radiological and clinical diagnosis of HVOO. Histologically the findings were of centrilobular patchy acute hemorrhage with centrilobular necrosis. There was no associated thrombosis, rejection, or steatosis (see Fig. 3). Exploratory laparotomy for cavoplasty was decided upon, but at the time of the operation, the finding of severe portal hypertension combined with a large, congested liver led to the procedure being abandoned. Interventional radiology then deployed stents in the cava and HV in an attempt to relieve HVOO (see Fig. 4). After 3 days, the stents thrombosed despite anticoagulation (see Fig. 5). The patient was relisted and successfully retransplanted a week later. The implanting technique was caval replacement on VV bypass.
920 KHORSANDI ET AL.
DISCUSSION PB transplant evolved to counter the physiological problems of caval replacement, but concerns remain that the advantages gained are negated by a higher incidence of HVOO. In the literature, the reported incidence of HVOO is < 2% for caval replacement,9,10 3% to 4% for PB,11,12 with the incidence increasing up to 5% to 15% in pediatric recipients and partial grafts.13 Considering the PB variants, the incidence of HVOO ranges from 2.4% to 6.4% for standard PB and 1.8% to 5.5% for side to side, with advocates of the 3 HV technique reporting 1%.11,12,22 In the present report, the overall incidence of early HVOO was low at 1%, making it a rare complication, classically, presenting at a month after transplant with progressive ascites and minimal derangement in graft biochemistry. In previous published series, there are typically 4 phases of HVOO described: (1) immediate graft congestion on reperfusion, requiring the anastomosis to be refashioned or the right diaphragm to be plicated to adjust for the mismatch between a small graft and hepatic bed11,14; (2) acute Budd-Chiari presenting with graft dysfunction and ascites within 48 hours generally requiring retransplant as the HVs have thrombosed; (3) ascites within 3 months that typically is managed with diuretics; and (4) chronic through a combination of intimal hyperplasia/fibrosis that is increasingly managed by interventional radiology before retransplant is considered.11,22 In the present study, there are a number of limitations. First, it is retrospective, not randomized and driven by institutional preference. Additionally, the early cases of HVOO for this study were identified by the presenting complaint of problematic ascites, which will have missed cases of HVOO that were identified intraoperatively with congestion on reperfusion and immediately amended surgically, either by re-fashioning the anastomosis or plicating the diaphragm. The other subset of early HVOO that would not of been captured in the present study design is the case of transient ascites that reflects a compromise to right HV outflow, which occurs in the 3 HV PB; in that case, the liver remodels to produce right lobe atrophy. When medical management for HVOO fails, there are a number of endovascular options in the form of angioplasty or stents. However, most experience on stenting for HVOO is from partial rather than whole grafts,13,23 and there is a reluctance to use this strategy early or in the presence of thrombosis because of the potential risk of anastomotic rupture.22,24 Another consideration is that stents can migrate, and if deployment is not carefully planned, they may compromise retransplant or cavoplasty.13,14 A number of different surgical strategies have been used to resolve HVOO such as termino-terminal rescue cavocavostomy,25 renosplenic shunt,26 cavoatrial shunt27 and side-to-side stapled cavocavostomy.28 Ultimately, if HVOO rescue strategies are unsuccessful, retransplant is then required.
LIVER TRANSPLANTATION, July 2015
In conclusion, early HVOO can be a graft-losing complication that highlights the technical vulnerabilities of the alternative implanting techniques. This study illustrates that early HVOO is rare, and there is no evidence from this study, as it is not sufficiently powered, that a given implantation technique is more vulnerable to developing early HVOO. However, early revisional surgery for HVOO can preserve graft function with retransplantation being reserved for cases where surgical cavoplasty or radiological stenting is technically not possible.
REFERENCES 1. Starzl TE, Marchioro TL, Vonkaulla KN, Hermann G, Brittain RS, Waddell WR. Homotransplantation of the liver in humans. Surg Gynecol Obstet 1963;117:659-676. 2. Calne RY, Williams R. Liver transplantation in man. I. Observations on technique and organization in five cases. Br Med J 1968;4:535-540. 3. Tzakis A, Todo S, Starzl TE. Orthotopic liver transplantation with preservation of the inferior vena cava. Ann Surg 1989;210:649-652. 4. L azaro JL, Charco R, Revhaug A, Murio E, Balsells J, Hidalgo E, et al. Hemodynamics in human liver transplantation with inferior vena cava preservation. Transplant Proc 1997;29:2851-2852. 5. Cescon M, Grazi GL, Varotti G, Ravaioli M, Ercolani G, Gardini A, Cavallari A. Venous outflow reconstructions with the piggyback technique in liver transplantation: a single-center experience of 431 cases. Transpl Int 2005; 18:318-325. 6. Belghiti J, Panis Y, Sauvanet A, Gayet B, F ek et e F. A new technique of side to side caval anastomosis during orthotopic hepatic transplantation without inferior caval occlusion. Surg Gynecol Obstet 1992;175:270-272. 7. Figueras J, Llado L, Ramos E, Jaurrieta E, Rafecas A, Fabregat J, et al. Temporary portocaval shunt during liver transplantation with vena cava preservation. Results of a prospective randomized study. Liver Transpl 2001;7:904-911. 8. Cherqui D, Lauzet JY, Rotman N, Duvoux C, Dhumeaux D, Julien M, Fagniez PL, et al. Orthotopic liver transplantation with preservation of the caval and portal flows. Technique and results in 62 cases. Transplantation 1994;58:793-796. 9. Settmacher U, N€ ussler NC, Glanemann M, Haase R, Heise M, Bechstein WO, Neuhaus P. Venous complications after orthotopic liver transplantation. Clin Transplant 2000;14:235-241. 10. Lerut J, Tzakis AG, Bron K, Gordon RD, Iwatsuki S, Esquivel CO, et al. Complications of venous reconstruction in human orthotopic liver transplantation. Ann Surg 1987;205:404-414. 11. Parrilla P, S anchez-Bueno F, Figueras J, Jaurrieta E, Mir J, Margarit C, et al. Analysis of the complications of the piggy-back technique in 1,112 liver transplants. Transplantation 1999;67:1214-1217. 12. Navarro F, Le Moine MC, Fabre JM, Belghiti J, Cherqui D, Adam R, et al. Specific vascular complications of orthotopic liver transplantation with preservation of the retrohepatic vena cava: review of 1361 cases. Transplantation 1999;68:646-650. 13. Ko GY, Sung KB, Yoon HK, Kim KR, Kim JH, Gwon DI, Lee SG, et al. Early posttransplant hepatic venous outflow obstruction: long-term efficacy of primary stent placement. Liver Transpl 2008;14:1505-1511. 14. Darcy MD. Management of venous outflow complications after liver transplantation. Tech Vasc Interv Radiol 2007; 10:240-245.
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15. John TG, Plevris JN, Redhead DN, Garden OJ, Finlayson ND, Sanfey HA. Massive ascitic fluid loss after liver transplantation. Gastroenterology 1996;111:564-565. 16. Nishida S, Gaynor JJ, Nakamura N, Butt F, Illanes HG, Kadono J, et al. Refractory ascites after liver transplantation: an analysis of 1058 liver transplant patients at a single center. Am J Transplant 2006;6:140-149. 17. Borsa JJ, Daly CP, Fontaine AB, Patel NH, Althaus SJ, Hoffer EK, et al. Treatment of inferior vena cava anastomotic stenosis with the Wallstent endoprosthesis after orthotopic liver transplantation. J Vasc Interv Radiol 1999;10:17-22. 18. Cirera I, Navasa M, Rimola A, Garcıa-Pag an JC, Grande L, Garcia-Valdecasas JC, et al. Ascites after liver transplantation. Liver Transpl 2000;6:157-162. 19. Kootstra G. Statement on non-heart-beating donor programs. Transplant Proc 1995;27:2965. 20. Muiesan P, Girlanda R, Jassem W, Melendez HV, O’Grady J, Bowles M, et al. Single-center experience with liver transplantation from controlled non-heartbeating donors: a viable source of grafts. Ann Surg 2005;242: 732-738. 21. Casavilla A, Ramirez C, Shapiro R, Nghiem D, Miracle K, Fung JJ, Starzl TE. Experience with liver and kidney allografts from non-heart-beating donors. Transplant Proc 1995;27:2898. 22. Wang SL, Sze DY, Busque S, Razavi MK, Kee ST, Frisoli JK, Dake MD. Treatment of hepatic venous outflow
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23.
24.
25.
26.
27.
28.
obstruction after piggyback liver transplantation. Radiology 2005;236:352-359. Buell JF, Funaki B, Cronin DC, Yoshida A, Perlman MK, Lorenz J, et al. Long-term venous complications after full-size and segmental pediatric liver transplantation. Ann Surg 2002;236:658-666. Weeks SM, Gerber DA, Jaques PF, Sandhu J, Johnson MW, Fair JH, Mauro MA. Primary Gianturco stent placement for inferior vena cava abnormalities following liver transplantation. J Vasc Interv Radiol 2000;11(part 1):177-187. Zamboni F, Sampietro R. Conversion to termino-terminal cavo-cavostomy as a rescue technique for infrahepatic obstruction after piggyback liver transplantation. Transpl Int 2008;21:1008-1010. Mazzaferro V, Regalia E, Pulvirenti A, Baratti D, Montagnino G, Bozzetti F. Renal-splenic shunt for infrahepatic occlusion after piggy-back liver transplantation. Transpl Int 1997;10:392-394. Eid A, Rahamimov R, Ilan Y, Tur-Kaspa R, Berlatzky Y. Cavoatrial shunt: a graft salvage procedure for suprahepatic caval anastomosis obstruction after liver transplantation. Liver Transpl Surg 1998;4:239-240. Quintini C, Miller CM, Hashimoto K, Philip D, Uso TD, Aucejo F, et al. Side-to-side cavocavostomy with an endovascular stapler: rescue technique for severe hepatic vein and/or inferior vena cava outflow obstruction after liver transplantation using the piggyback technique. Liver Transpl 2009;15:49-53.
