Endoscopic Retrograde Cholangiopancreatography in Patients With Biliary Complications After Orthotopic Liver Transplantation: Outcomes and Complications C. Sanna, G.M. Saracco, D. Reggio, F. Moro, A. Ricchiuti, P. Strignano, S. Mirabella, G. Ciccone, and M. Salizzoni ABSTRACT Biliary complications after orthotopic liver transplantation (OLT) still remain a major cause of morbidity and mortality. The most frequent complications are strictures and leakages in OLT cases with duct-to-duct biliary reconstruction (D-D), which can be treated with dilatation or stent placement during endoscopic retrograde cholangiopancreatography (ERCP), although this procedure is burdened with potentially severe complications, such as retroperitoneal perforation, acute pancreatitis, septic cholangitis, bleeding, recurrence of stones, strictures due to healing process. The aim of the study was to analyze the outcome of this treatment and the complications related to the procedure. Among 1634 adult OLTs, we compared postprocedural complications and mortality rates with a group of 5852 nontransplanted patients (n-OLTs) who underwent ERCP. Of 472 (28,8%) post-OLT biliary complications, 319 (67.6%) occurred in D-D biliary anstomosis cases and 94 (29.5%) patients underwent 150 ERCP sessions. Among 49/80 patients (61.2%) who completed the procedure, ERCP treatment was successful. Overall complication rate was 10.7% in OLT and 12.8% in n-OLT (P ⫽ NS). Compared with the n-OLT group, post-ERCP bleeding was more frequent in OLT (5.3% vs 1.3%, P ⫽ .0001), while the incidence of pancreatitis was lower (4.7% vs 9.6%, P ⫽ .04). Procedure-related mortality rate was 0% in OLT and 0.1% in n-OLT (P ⫽ NS). ERCP is a safe procedure for post-OLT biliary complications in the presence of a D-D anastomosis. Morbidity and mortality related with this procedure are acceptable and similar to those among nontransplanted population. ILIARY COMPLICATIONS after orthotopic liver transplantation (OLT) are a major cause of morbidity and mortality because of their frightful consequences as well as high rates reported by larger series in the literature (6%– 40%).1– 8 Usually during OLT the biliary tract is reconstructed using a duct-to-duct anstomosis (D-D), such as choledochocholedochostomy or hepaticocholedochostomy, or, less frequently, by Roux-en-Y hepaticojejunostomy. The most common complications after OLT are anastomotic strictures and biliary fistulae; extrahepatic stones and ampullary dysfunction are more rare.9 Treatment options for biliary complications have changed during the past decade. Presently, it is well established that a multidisciplinary approach should involve endoscopists, interventional radiologists, and transplant surgeons. Anastomotic strictures and bilary leakages may be treated using dilatation
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and/or stent placements during endoscopic retrograde cholangiopancreatography (ERCP) in transplanted patients with a D-D biliary anstomosis. ERCP-related complications may be serious, but they are not frequent. The most common ERCP-related complications are pancreatitis (10% reported in literature)10 and bleeding; seldom are cases of cholangitis and perforation.
From the Centro trapianti di fegato “E.S. Curtoni” (C.S., D.R., F.M., A.R., P.S.P., S.M., M.S.), ASOU S. Giovanni Battista, Corso Bramante 88, Torino, Italy, and Dipartimento di Gastrenterologia Universitaria (G.M.S.), Torino, Italy; and the Department of Epidemiology of Tumours (G.C.), CPO Piemonte, Torino, Italy. Address reprint requests to Alessandro Ricchiuti, Centro trapianti di fegato “E.S. Curtoni,” ASOU S. Giovanni Battista, Corso Bramante 88, Torino, Italy. E-mail:
[email protected]
© 2009 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.03.086
Transplantation Proceedings, 41, 1319 –1321 (2009)
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SANNA, SARACCO, REGGIO ET AL Table 1. Demographic Data
Number of patients Number of procedures Number of complete procedures Mean age ⫾ SD (range) Sex
OLT
n-OLT
94 150
5852 6189
136 (90.7%) 52 ⫾ 9.6 (22–68) M: 72 (77%) F: 22 (23%)
P
5632 (91%)
NS
68 ⫾ 19 (18–105)
.0001
M: 2581 (44%) F: 3271 (56%)
.0001
OLT, liver transplantation group; n-OLT, nontransplanted group; SD, standard deviation; NS, not significant.
Late complications include cicatricial strictures of the Oddi sphincter or bile stone relapses. Herein, we have described the ERCP indications and outcomes among a population of OLT patients in our center. Moreover, we compared the overall ERCP-related complication rate in OLT patients with a control group consisting of nontransplanted patients (n-OLT) who underwent diagnostic or therapeutic ERCP. PATIENTS AND METHODS From October 1990 to December 2007, 1733 OLTs were performed in 1587 patients in our center. We excluded pediatric recipients and patients with less than 2 days’ survival after OLT, yielding 1634 OLTs with 1353 (83%) undergoing a D-D biliary anastomosis, while a Roux-en-Y anastomosis was performed in 279 (17.1%). We analyzed biliary complications leading to ERCP as well as the success, morbidity, and mortality rate, of this therapy compared with 5852 n-OLT patients who underwent ERCP in the same period. Statistical analyses were performed using SPSS program (SPSS Inc, Chicago Ill, version 12.02). Continuous variables were described as median (maximum–minimum), and the difference between groups was verified with nonparametric tests (MannWhitney, Kruskal-Wallis, or Wilcoxon). Categorical variables were described as incidences. Differences between groups were estimated with chi-square test (Pearson) or exact test. Odds ratios were calculated as risk estimates.
RESULTS
A surgical, radiological, or endoscopic treatment was attempted in 391 cases among 472 (28.8%) biliary complications, which affected 402 (24.6%) OLTs. The overall most frequent biliary complication was an extrahepatic stricture (10.8%), followed by biliary leakage (7%). Among 1353 patients with a D-D anstomosis, 319 (23.6%) developed a biliary complication and 94 (24.5%) underwent ERCP. In some cases, more than one ERCP session was needed, so the overall number of ERCP sessions was 150. In 14/94 cases (14.9%), it was not possible to complete the diagnostic or therapeutic session because of a noncompliant patient or due to technical/anatomic difficulties. Among the 49/80 (61.2%) patients in whom the procedure was completed, the ERCP was curative. In
contrast, 31/80 (38.8%) patients had no resolution of the biliary complication with ERCP. In 15 (48.4%) of these patients, it was necessary to perform an hepaticojejunostomy; in 5 (16.2%), an additional percutaneous approach was needed, and 10 (32.2%) underwent a multidisciplinary treatment involving endoscopic, interventional radiological, and surgical approaches; Only one patient (3.2%) with native sclerosing cholangitis did not experience a resolution and required retransplantation. Available demographic data of the OLT and n-OLT groups are reported in Table 1. The two groups were not similar for age or sex, because the n-OLT group was older and included more women. Indications for ERCP obviously differed between the two group as shown in Table 2: in the n-OLT group, the major problems were lithiasis, intra- or extrahepatic malignancies, and biliary pancreatitis, while in OLT patients, anastamotic strictures, lithiasis, and functional cholestasis were the more frequent causes demanding ERCP. Overall, ERCP-related complications were similar between OLT and n-OLT patients, as shown in Table 3 (10.75% vs 12.8%; P ⫽ NS). Bleeding after sphincterotomy was more frequent among the OLT population, namely, 5.3% versus 1.3% among n-OLT patients (P ⫽ .0001), whereas the rate of pancreatitis was greater in the n-OLT patients (9.6% vs 4.7%; P ⫽ .0406). The mortality rates related to the endoscopic procedure were 0% in OLT and 0.1% (in agreement with literature10,11) in n-OLT groups (P ⫽ NS). DISCUSSION
ERCP is an endoscopic procedure that allows the physician to place a cannula in the biliary tract to opacify the primary biliary duct, intrahepatic biliary tree, and Wirsung duct. ERCP has gained an ever-growing therapeutic role, despite its traditional diagnostic function. When a biliary complication after OLT is found, ERCP can be of use to solve anastamotic strictures or biliary stones. Moreover, bilary leakage or T-tube-related complications can be treated with stent placement during ERCP. However, indications for ERCP after OLT are restricted to D-D anastomoses; routine use of ERCP after OLT is not recommended because of the high risk of cholangitis in Table 2. Indications to ERCP in Both Groups
Biliary stones Neoplastic biliary strictures Biliary acute pancreatitis Iatrogenic biliary fistula Obstructive chronic pancreatitis Cholangitis sclerosing primitive Benign biliary strictures Oddi’s sphincter disease Cholestasis
OLT
n-OLT
40 (26.7%) 0 0 10 (6.7%) 0 2 (1.3%) 72 (48%) 0 26 (17.3%)
3211 (51.8%) 1208 (19.5%) 964 (15.5%) 286 (4.6%) 174 (2.8%) 156 (2.5%) 102 (1.6%) 32 (0.5%) 56 (0.9%)
ERCP, endoscopic retrograde cholangiopancreatography; OLT, liver transplantation group; n-OLT, nontransplanted group.
ERCP IN PATIENTS WITH BILIARY COMPLICATIONS
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Table 3. ERCP-Related Complications
Pancreatitis Bleeding Cholangitis Bradycardia Hipoxya Perforation Death Overall complications
OLT
n-OLT
P
Relative Risk
95% Confidence Interval
7 (4.7%) 8 (5.3%) 1 (0.7%) 0 0 0 0 16 (10.7%)
596 (9.6%) 76 (1.3%) 68 (1.1%) 21 (0.3%) 21 (0.3%) 6 (0.1%) 8 (0.1%) 796 (12.8%)
.0406 .0001 .6143 .4749 .4749 .7028 .6595 .4267
1.05 0.95 1.00 1.00 1.00 1.00 1.00 1.02
1.01–1.09 0.92–0.99 0.99–1.01 1.00–1.00 1.00–1.00 1.00–1.00 1.00–1.00 0.96–1.08
ERCP, endoscopic retrograde cholangiopancreatography; OLT, liver transplantation group; n-OLT, nontransplanted group.
immunosuppressed patients, even if we observed a low rate of this complication. In addition, interventional radiological and surgical approaches seem to be safe and useful in these cases. Finally, biliary problems that can be treated by an endoscopic approach are somewhat rare.12 We observed that the ERCP-related complication rate was low; especially the pancreatitis incidence was significantly lower among OLT patients. The low rate of complications of ERCP after OLT did not differ from a control population consisting of nontransplanted patients, even though the two populations were not uniform concerning demographic data, type of disease, and comorbidity. Instead, they were homogeneous regarding the technical endoscopic procedure and the operating equipment. The mortality rate related to the endoscopic procedure was 0% among OLTs and 0.1% among n-OLTs in agreement with the literature.10,11 In conclusion, ERCP is a safe procedure that increases the range of diagnostic and therapeutic opportunities for post-OLT biliary complications in the presence of a D-D anastomosis. Morbidity and mortality related to this procedure are acceptable and similar to those among a nontransplanted population. REFERENCES 1. Friend PJ: Overview: biliary reconstruction after liver transplantation. Liver Transplant Surg 1:153, 1995
2. Verdonk RC, Buis CI, Porte RJ, et al: Biliary complications after liver transplantation: a review. Scand J Gastroenterol Suppl 243:89, 2006 3. Hampe T, Dogan A, Encke J, et al: Biliary complications after liver transplantation. Clin Transplant 20(suppl 17):93, 2006 4. Riyadh Khuroo MS, Al Ashgar H, Khuroo NS, et al: Biliary disease after liver transplantation: the experience of the King Faisal Hospital an Research Center. Gastroenterol Hepatol 20:217, 2005 5. Pascher A, Neuhaus P: Biliary complications after deceaseddonor orthotopic liver transplantation. Hepatobiliary Pancreat Surg 13:487, 2006 6. Rerknimitr R, Sherman S, Fogel E, et al: Biliary tract complications after orthotopic liver transplantation with choledochocholedochostomy anastomosis: endoscopic findings and results of therapy. Gastrointest Endosc 55:224, 2002 7. Tung BY, Kimmey MB: Biliary complications of orthotopic liver transplantation. Dig Dis 17:133, 1999 8. Greif F, Bronsther OL, Van Thiel DH, et al: The incidence, timing, and management of biliary tract complications after orthotopic liver transplantation. Ann Surg 219:40, 1994 9. Thuluvath PJ, Pfau PR, Kimmey MB, et al: Biliary complications after liver transplantation: the role of endoscopy. Endoscopy 37:857, 2005 10. Bilbao MK, Dotter CT, Lee TG, et al: Complications of endoscopic retrograde cholangiopancreatography (ERCP): a study of 10000 cases. Gastroenterology 70:314, 1996 11. Vandervoort J, Soetikno RM, Tham TCK, et al: Risk factors for complications after performance of ERCP. Gastrointest Endosc 56:652, 2002 12. Shah SR, Dooley J, Agarwal R: Routine endoscopic retrograde cholangiography in the detection of early biliary complications after liver transplantation. Liver Transpl 8:491, 2002