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Long-term follow-up after biliary stent placement for postoperative bile duct stenosis
Long-term follow-up after biliary stent placement for postoperative bile duct stenosis Jacques J. G. H. M. Bergman, MD, Lotje Burgemeister, MD, Marco J. Bruno, MD, Erik A. J. Rauws, MD, Dirk J. Gouma, MD, Guido N. J. Tytgat, MD, Kees Huibregtse, MD Amsterdam, The Netherlands
Background: The outcome of temporary biliary stent placement for postoperative bile duct stenosis was retrospectively evaluated with the main aim of assessing long-term complications after stent removal. Methods: ERCP was performed between 1981 and 1991 in 74 patients with postoperative bile duct stenoses. Two 10F stents were inserted for a maximum of 12 months with stent exchange every 3 months to avoid cholangitis caused by clogging. Results: Stent insertion failed in 11 patients with complete and 4 patients with incomplete biliary obstruction. Early complications occurred in 14 patients (19%) including 2 deaths. Therefore 57 patients were included in the stent phase of the study. In 10 patients the referring physician did not adhere to the treatment protocol, and nonelective stent exchange for jaundice and/or cholangitis was necessary in 7 (70%). Of the 47 patients treated according to protocol, complications developed in 40% during the period with stents in situ. Stents were eventually removed in 44 patients who were subsequently followed for a median of 9.1 years. Late complications developed in 15 patients (34%) including recurrent stenosis in 9 (20%). All cases of recurrent stenosis occurred within 2 years of stent removal. Conclusions: Endoscopic treatment is feasible in 80% of patients who undergo an ERCP for postoperative bile duct stenosis. After stent insertion and during the time with stents in situ, complications occur at a significant rate but are usually mild or reflect the patient’s underlying condition. After stent removal, recurrent stenosis develops in 20% of patients within 2 years of stent removal. Endoscopic treatment should be the initial management of choice for postoperative bile duct stenosis. (Gastrointest Endosc 2001;54:154-61.)
Postoperative bile duct injuries occur in 0.2% to 0.5% of patients undergoing open cholecystectomy and in 0% to 2.7% after laparoscopic cholecystectomy.1,2 Four types of surgical bile duct injury can be identified3: type A, leakage from minor bile ducts (cystic duct or peripheral hepatic radicles); type B, leakage from major bile ducts (common bile duct, common hepatic duct, left or right main hepatic ducts); type C, bile duct stenoses without bile leakage; and type D, complete transection of the duct with or without excision of some portion of the biliary tree. Minor and major bile duct leaks are best treated endoscopically with temporary placement of biliary Received June 29, 2000. For revision September 5, 2000. Accepted April 13, 2001. From the Department of Gastroenterology and Hepatology and the Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands. Presented in part at the annual meeting of the American Society for Gastrointestinal Endoscopy, May 16-19, 1999, Orlando, Florida (Gastrointest Endosc 1999;49:AB178). Reprint requests: J.J.G.H.M. Bergman, MD, Department of Gastroenterology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Copyright © 2001 by the American Society for Gastrointestinal Endoscopy 0016-5107/2001/$35.00 + 0 37/1/116455 doi:10.1067/mge.2001.116455 154
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stents and/or endoscopic sphincterotomy, whereas surgical treatment is required in all patients with complete ductal transections (type D lesions).3 For patients with postoperative bile duct stenosis (type C lesions, Fig. 1), the choice between endoscopic or surgical management is less clear. Traditionally, these lesions have been treated with reconstructive surgery (mainly hepaticojejunostomy).4-6 However, over the last decade there have been many efforts to explore endoscopic management.7-10 Endoscopic treatment usually involves temporary placement of 1 or more stents through the stenosis to achieve gradual and permanent dilation of the fibrotic tissue in the strictured segment. Stents are usually kept in situ for up to 1 year with trimonthly exchange to prevent cholangitis. The premise of endoscopic treatment is that once the stenosis is adequately dilated, the fibrotic tissue will undergo remodeling thereby preventing elastic recoil and recurrence of the stenosis after removal of the stents. Published experience with this form of endoscopic management has been favorable, but all studies refer only to early results. The most important criticism of endoscopic management relates to the unknown, long-term outcome of these patients. It is claimed that many stenoses will eventually recur VOLUME 54, NO. 2, 2001
Follow-up after biliary stent placement for postoperative bile duct stenoses
A
B
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C
D
Figure 1. Retrograde cholangiograms in patient with subhilar bile duct stenosis after laparoscopic cholecystectomy. There is gradual disappearance of the stenosis during stent therapy. A, Cholangiogram before treatment. B, After 3 months with stent in situ. C, After 6 months with stent in situ. D, After 12 months with stent in situ: the stenosis has been dilated adequately.
and that surgery will be required at a later time under less favorable conditions (older age, secondary biliary cirrhosis, and secondary changes in the biliary system caused by the long-term presence of the stents). Therefore a long-term follow-up study was performed in all patients who were treated by temporary biliary stent placement for postoperative bile duct stenoses between 1981 and 1991. PATIENTS AND METHODS All patients who underwent ERCP between January 1981 and January 1991 for diagnosis and management of postoperative bile duct stenosis were included. Bile duct stenosis was defined as a luminal narrowing of the bile duct with proximal dilation demonstrated by cholangiography.10 Patients were only included if they had symptoms (jaundice, cholangitis) or signs (progressive cholestatic liver function tests) of biliary obstruction before the ERCP. Patients with malignant stenoses or benign stenoses caused by chronic pancreatitis, primary sclerosing cholangitis, or choledocholithiasis were excluded. Also excluded were patients with postsphincterotomy stenoses or biliodigestive anastomoses. A total of 74 patients fulfilled these selection criteria. This cohort of patients has been previously described.11 In the present study 6 patients were excluded from the cohort: 5 with stenoses of biliodigestive anastomoses and 1 who in retrospect most likely had a malignant biliary stenosis. Treatment protocol After obtaining a diagnostic cholangiogram and documentation of the site and extent of the stenosis, attempts were made to pass a hydrophilic guidewire and diagnostic VOLUME 54, NO. 2, 2001
PHASE: Stent Insertion
.................................................................................................................................................................................................................. Referred for ERCP N=74 Failed stent insertion (n=15) total stop (n=11), no passage of guide wire (n=3), restlessness (n=1)
Complications (n=14, 19%) Failed ERCP, cholangitis, death (n=1) Pancreatitis, death (n=1) Cholangitis (n=6) Bleeding (n=4) Pancreatitis (n=2)
Stent insertion successful N=59 Early death (n=1) Surgery, patient preference (n=1)
Stent in situ
Stent in situ phase .................................................................................................................................................................................................................. N=57 Complications (n=7, 70%) Cholangitis and/or jaundice, No adherence to protocol, stent exchange (n=5) treated elsewhere (n=10) Cholangitis, death (n=2) Stent in situ phase, treated according to protocol N=47 Complications (n=19, 40%) Fever after elective ERCP (n=7) Cholangitis, stent exchange (n=5) Cholestasis, stent exchange (n=5) Stent migration, surgery (n=2) Follow-up Stents removed .................................................................................................................................................................................................................. N=44 Restenosis (n=9) Surgery (n=4) Repeated stenting (n=5) Unrelated deaths (n=2) Stent migration, surgery (n=1)
Other complications: (n=6) Cholangitis, ERCP stones (n=2) Cholangitis, no ERCP (n=1) Fever of unknown cause (n=1) Variceal bleeding, death (n=1) Transient pain & cholestasis (n=1)
Median follow-up: 9.1 years (2 mo-15yrs)
Deaths: (n=16) Variceal bleeding (n=2) Cardiac infarction post-ERCP (n=1) Multiorgan failure eci (n=1) Unrelated (n=12)
Figure 2. Flow diagram of outcomes of endoscopic management in 74 patients with postoperative bile duct stenosis. catheter through the stenosis. If the stenosis was too tight to allow passage of the catheter, dilating catheters of gradually increasing diameter (2-3 mm outside diameter) were passed over the guidewire and through the stenosis, sometimes with supplemental balloon dilatation. There was no GASTROINTESTINAL ENDOSCOPY
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Table 1. Baseline characteristics of patients N = 74 (%) Presenting symptoms Jaundice Cholangitis Cholestatic liver function tests Bile leakage/abnormal T-tube cholangiography Unknown Surgical history* Cholecystectomy ± common bile duct exploration, single operation Cholecystectomy ± common bile duct exploration, direct injury repair Cholecystectomy, repeated common bile duct exploration Unknown† Localization of the stenosis (Bismuth19) Common bile duct Within 2 cm distal from bifurcation Bifurcation Hepatic ducts Right hepatic duct Concomitant bile leakage Bile duct stones
33 20 12 7 2
(45) (27) (16) (9) (3)
48 (65) 15 (20) 9 (12) 2 (3) 39 29 3 1 2 14 17
(53) (39) (4) (1) (3) (19) (23)
*No laparoscopic procedure were performed in the cohort of patients (1981-1991). †Type of biliary surgery performed in these patients could not be determined.
standardized protocol concerning balloon dilation or catheter dilation before stent placement. An Amsterdamtype straight polyethylene stent was then inserted over the guidewire and catheter, thus bridging the stenosis. The treatment protocol specified placement of two 10F stents if possible. For multiple stent insertion, an endoscopic sphincterotomy was performed to facilitate stent placement. With tight stenoses sometimes only a 7F or a single 10F stent could be placed. In such cases, the single stent was exchanged for two 10F stents after 6 weeks, and then the 2 stents were subsequently exchanged every 3 months to avoid cholangitis caused by clogging. The maximum treatment period with 2 stents in situ was 12 months. The stents were not replaced if the stenosis was considered to be adequately dilated based on the following criteria as subjectively assessed by the endoscopist: (1) adequate dilation of the stenosis on cholangiography, (2) satisfactory drainage of contrast from the biliary tree, (3) passage of a diagnostic catheter and extraction balloon through the stenosis without encountering significant resistance. Before ERCP, all patients were treated prophylactically by intravenous administration of antibiotics (amoxicillin and gentamycin). In the absence of cholangitis as an indication for the ERCP, no antibiotics were given after the procedure. Informed consent was obtained from all patients. Outcome parameters and sources of information Three different treatment phases were defined retrospectively: (1) stent insertion phase: period between first attempt at stent placement and discharge from the hospital, (2) stent in situ phase: period during which stents 156
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remained in situ including stent exchange every 3 months, and (3) follow-up phase: period between final removal of the stents and end of follow-up. Complications were noted and graded as to severity according to 1991 consensus guidelines.12 Information concerning the stent insertion and stent in situ phases was obtained from our endoscopy reports and medical records at referring hospitals. Because follow-up after stent removal comprised a period up to 15 years, information pertinent to the follow-up phase was obtained from multiple sources to ensure that data collection was complete. First, the primary care physicians for all patients were contacted by telephone and were asked to check the patients’ files for any medical problems since stent removal. Second, all patients alive at the point of data collection were contacted by telephone and asked about any medical problems since removal of the stents. Subsequently these patients were asked to complete a postal questionnaire that inquired about recurrence of biliary symptoms and related diagnostic or therapeutic interventions. Patients who did not respond were recontacted by telephone. Third, all patients were invited to have a blood sample taken for the following liver function tests: bilirubin (conjugated and deconjugated), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transferase. Again, those who did not respond were contacted by telephone. If the patient had died, the primary care physician and the patient’s family were contacted to determine the cause of death and medical history after stent removal. If one or more of the above-mentioned sources of information suggested that biliary-related complications had occurred, the attending physician was contacted and the medical records at the local hospital were inspected. If a questionnaire and/or liver function tests indicated the possibility of biliary pathology, the patient was invited to undergo further diagnostic testing. Predictors of restenosis during follow-up Univariate and multivariate analyses were performed to determine whether there were any patient characteristics that could predict the occurrence of restenosis during follow-up. The following potential factors were evaluated: age, gender, time interval between surgery and diagnosis of the stenosis, anatomic location of the stenosis, presence of bile leakage, and the number of ERCPs required to achieve initial stent placement.
RESULTS Patient characteristics ERCP with stent insertion was attempted in 74 patients (33 men, 41 women; median age 62 years, range 19-84 years; Fig. 2). Patients either had symptoms at presentation or had evidence of progressive cholestasis after recent hepatobiliary surgery with peroperative repair of an injury to the biliary tree (Table 1). Presenting symptoms, prior surgical history, and diagnostic findings at ERCP are shown in Table 1. VOLUME 54, NO. 2, 2001
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Stent insertion phase A diagnostic cholangiogram was obtained in all patients (Table 1, Fig. 2). Stent insertion was successful in 59 patients (80%) after a mean of 1.4 procedures (range 1-7). In 2 patients a rendezvous procedure after percutaneous transhepatic cholangiography was necessary for successful endoscopic stent placement. Reasons for unsuccessful stent insertion were as follows: total obstruction in the bile duct (n = 11), successful proximal cholangiography but inability to pass a guidewire through stenosis (n = 3), and patient restlessness during ERCP (n = 1). Details concerning further management and early complications in these patients are given in Table 2. Patients in whom stent insertion was unsuccessful are only considered in the analysis of early complications of ERCP. Early complications occurred in 14 patients (19%): fever/cholangitis (n = 7), postsphincterotomy bleeding (n = 4), and pancreatitis (n = 3). Two patients died shortly after ERCP. The first was an 82-year old woman in whom stent insertion was unsuccessful because of total biliary obstruction. She refused further treatment and died of ongoing cholangitis and sepsis 10 days after the ERCP. The second patient died of a cerebral infarction during intensive treatment for a severe pancreatitis. All other early complications were graded as mild. Stent-in-situ phase Of the 59 patients in whom stent insertion was initially successful, 1 died of a severe pancreatitis (see previous section) and 1 preferred to undergo elective hepaticojejunostomy. A total of 57 patients therefore entered the stent-in-situ phase (Fig. 2). Forty-eight patients received 2 stents; 9 had only 1 stent inserted. Ten patients were lost to follow-up during the stent-in-situ phase. For these patients the referring physician did not adhere to the treatment protocol and further management was not carried out in our unit. Outcomes for these patients were determined retrospectively. The further management of these patients, who were generally elderly and had significant comorbid conditions, was highly variable and mainly triggered by signs of stent dysfunction. Seven patients (70%) underwent 1 or more stent exchange procedures (range 1-14) after developing jaundice and/or cholangitis. Nine died during follow-up with stents in situ. In 2 patients death was due to cholangitis secondary to stent dysfunction. Two patients did not develop any complications and died of unrelated causes. One patient was alive at the time of follow-up. Eventually she had her stents removed after 3 episodes of stent therapy. Compared with the other 47 patients who entered the stent-in-situ phase, the VOLUME 54, NO. 2, 2001
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Table 2. Further management and outcome for 15 patients with postoperative bile duct stenosis in whom stent insertion was unsuccessful N = 15 Expectant management Died of ongoing cholangitis No problems during follow-up Hepaticojejunostomy Bile leakage Bleeding/sepsis Pulmonary embolism
2 1 1 13 1 1 1
Total cohort comprised 74 patients.
10 lost to follow-up during this phase had a higher median age (79 years vs. 58 years; p < 0.00l MannWhitney test). There were no significant differences with respect to location and extent of the stenoses. Of the 47 patients who completed the stent-in-situ phase according to protocol, 19 (40%) experienced complications while the stents were in place (Fig. 2). In 10 patients nonelective stent exchange was necessary because of jaundice or cholestatic lever function tests (n = 6), or cholangitis (n = 4). After stent exchange, symptoms resolved and the complication was graded mild in all cases. Seven patients developed fever after an elective stent exchange and were treated with antibiotics. Two severe complications were encountered during the stent-in-situ phase for which surgery was eventually required. In 1 patient a stent had migrated into the duodenum and could not be retrieved endoscopically. He underwent laparotomy for stent removal but continued to undergo endoscopic treatment according to protocol. In the second patient the stent had migrated into the bile duct and could not be retrieved during ERCP. This patient underwent elective surgery with stent removal and hepaticojejunostomy. Two patients died during the stent-in-situ phase of unrelated causes. Follow-up phase Forty-four patients (20 men, 24 women, median age 57 years, range 19-83 years) completed the stent-in-situ phase according to protocol and eventually had their stents removed (Fig. 2). All patients or relatives were contacted in addition to 96% of their primary care physicians. Of the patients alive at the time of data collection, 86% completed the questionnaire and 93% had a blood sample taken. The median period of follow-up in these 44 patients was 9.1 years (range 2 months-15 years). Fifteen patients (34%) developed complications during follow-up (Fig. 2). Stenosis recurred in 9 patients at a median of 2.6 months (range 1 week-2 years) after stent removal. Presenting symptoms were as follows: cholangitis (n GASTROINTESTINAL ENDOSCOPY
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Table 3. Further management in 9 of 44 patients with postoperative bile duct stenoses that recurred after temporary placement of biliary endoprostheses N=9 Reconstructive surgery Hepaticojejunostomy* Choledochoduodenostomy† Repeated stent therapy Unsuccessful stent therapy: hepaticojejunostomy‡ Stented until unrelated death Stented, died of myocardial infarction after ERCP Repeated stent therapy (3 times)‡
Figure 3. Kaplan-Meier plot showing proportion of patients without signs of restenosis among 44 patients with postoperative biliary stenosis who underwent stent placement and eventually had their stents removed.
= 6), upper abdominal pain and cholestasis (n = 2), and jaundice (n = 1). Symptoms were graded mild in all cases. ERCP demonstrated recurrence of the original stenosis in all 9 patients with proximal bile duct stones in 2. A Kaplan-Meier plot showing the proportion of patients without signs of restenosis is shown in Figure 3. Of the patients with recurrent stenosis, all but one presented within the first 6 months after stent removal. In patients followed more than 2 years, no cases of restenosis were found. The preferred treatment of recurrent stenoses was surgical reconstruction. Some patients, however, refused surgery or were considered extremely poor candidates and were thus again treated endoscopically. The management and longterm outcomes of the 9 patients who developed recurrent stenoses are summarized in Table 3. Apart from the 9 patients with symptoms related to recurrent stenosis, 6 developed other complications during follow-up. Two underwent ERCP for removal of bile duct stones. At ERCP there was no evidence of restenosis. After stone removal these 2 patients were followed for 2 and 13 years, respectively, during which time there were no further complications. Fever developed in one patient and he had cholestatic liver function tests 1 year after removal of the stents. ERCP was not performed because symptoms resolved spontaneously. This patient was followed for 9 years, during which time there were no further complications, and he died of an unrelated cause. The complications in these 3 patients were graded as mild. Another patient was hospitalized 6 years after stent removal because of 158
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4 3 1 5 2 1 1 1
*One patient with 6 years of event-free follow-up; 1 patient with 4 episodes of cholangitis in the first 2 years followed by event-free follow-up until unrelated death after 11 years; 1 patient with secondary biliary cirrhosis diagnosed at the time of surgery who died of variceal bleeding 4 years after surgery. †Six years after surgery 1 episode of jaundice caused by ductal stones, removed at ERCP. ‡No complications since last intervention (event-free follow-up >3 years in all).
fever, and a lesion was found by US in the liver. USguided aspiration was performed twice and yielded no pus, and cultures remained negative. The fever resolved spontaneously and there were no problems during a further 4 years of follow-up. This complication was graded as moderate. An 80-year-old man was hospitalized 7 years after stent removal because of abdominal pain and cholestatic liver function tests. The symptoms resolved spontaneously and, because of the overall poor condition of the patient, an expectant treatment policy was adopted. A year later he died of shock and multi-organ failure without a clearly defined cause. This complication was graded as severe and most likely biliary in origin. Last, a patient with secondary biliary cirrhosis and varices at the time of initial stent insertion died 10 years after stent removal because of variceal bleeding. Several ERCPs were performed to check for restenosis, but the bile duct was found to be patent on all occasions. This complication was graded as severe and related to the underlying disease. Deaths during follow-up phase Sixteen of the 44 patients (36%) died during follow-up (Fig. 2); 4 deaths (9%) were biliary related. The first patient died of shock and multi-organ failure 1 year after a period during which he had abdominal pain and cholestatic liver function tests (see previous section). Two patients died as a result of variceal bleeding caused by liver cirrhosis. In 1 of these patients biliary cirrhosis was present when the stenosis was diagnosed (see previous section); in the second patient it was diagnosed at the time of reconVOLUME 54, NO. 2, 2001
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structive surgery for restenosis. One patient died of a myocardial infarction 1 day after an elective ERCP for stent exchange. In this patient the stenosis had recurred at 2 months after stent removal. He refused surgery and was treated endoscopically with stent insertion and exchange every 3 months. Questionnaires and liver function tests Of the 28 patients alive at the time of follow-up, 24 (86%) returned the questionnaire and none reported any biliary-related symptoms. Blood samples were obtained in 26 patients (93%) and mild cholestatic liver function tests (<3 times upper limit of normal) were found in 4. In 1 patient these abnormalities were due to biliary cirrhosis that had been diagnosed before the initial diagnosis of biliary stenosis. In another patient the liver function abnormalities were stable and due to atrophy of 2 segments of the right liver lobe that in retrospect were never drained endoscopically. The third patient with mild cholestatic liver function tests underwent magnetic resonance cholangiopancreatography that demonstrated no evidence of recurrent stenosis. The fourth patient, who lived abroad, refused further evaluation. Predictors of restenosis during follow-up To determine whether there were any patient characteristics that predicted restenosis during follow-up, the following factors were tested in univariate and multivariate models: age, gender, time interval between initial surgery and diagnosis of the stenosis, anatomic location of the stenosis, presence of bile leakage, and the number of ERCPs required for initial stent placement. None of these were statistically significant. DISCUSSION The endoscopic management of postoperative biliary stenosis currently involves stent placement, usually two, followed by stent exchange every 3 months for a maximum treatment period of 12 months.7,8-10 Treatment divides into 3 phases: stent insertion, stent-in-situ (including trimonthly stent exchange), and follow-up after stent removal. Stent insertion phase Endoscopic treatment of total ductal obstruction is not possible. Because ERCP is required for diagnosis, treatment of these patients is regarded as unsuccessful. In a strict sense, these patients do not have a true stenosis. Other studies have therefore included only patients with incomplete ductal stenosis.10,13 Dumonceau et al.10 successfully inserted stents in 47 of 48 patients (98%) with incomplete postoperative bile duct stenoses, a rate comparable VOLUME 54, NO. 2, 2001
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with the 94% in our study. Early complications of the stent insertion phase are mainly sphincterotomyrelated or are a reflection of the pretreatment condition of the patient (e.g., fever associated with bile leakage). Early complications developed in 19% of our patients. Dumonceau et al.10 encountered early complications in 6 of 48 patients (12.5%), whereas Costamagna et al.13 observed 4 complications in 42 patients (9.5%) who had stents placed for postoperative biliary stenoses. The present study focused on long-term outcome for patients who underwent endoscopic treatment 10 to 15 years earlier. Therefore, the relatively high early complication rate of 19% may not reflect current endoscopic practice. Stent-in-situ phase Because stents were in situ for a period of up to 1 year, complications were relatively common: 40% of patients had 1 or more complications during the stentin-situ period. Fever after elective stent exchange, in all cases effectively managed conservatively with antibiotics, and symptoms caused by stent dysfunction accounted for the majority of these complications. Stent dysfunction mainly occurred in patients whose referring physicians did not adhere to the protocol for elective stent exchange every 3 months. The present study includes patients who were treated when endoscopic management of postoperative bile duct stenosis was in the early stages of development. Since then, endoscopic treatment of these patients has become more established. Currently, when ERCP is electively performed at 3-month intervals, complications caused by stent dysfunction are mild and occur in 10% to 15% of patients over the 1 year during which stents remain in situ.13 Ten patients in the stent-in-situ phase of treatment were often lost to follow-up because of a failure to adhere to the treatment protocol. Only in retrospect was the overall poor outcome of these patients established: 70% developed complications during the in situ phase and in 2 patients death was due to cholangitis resulting from stent dysfunction. Although selection bias on the part of attending physicians cannot be excluded (patients lost to follow-up were significantly older than patients who completed the treatment protocol), the poor outcome in these patients underscores the need for strict adherence to the treatment protocol. In the present study, all patients who were treated according to protocol eventually had their stents removed, whereas Dumonceau et al.10 were able to remove the stents in 95% of their patients. However, some of the instances of stricture recurrence in both studies occurred shortly after stent removal and these cases might be considered treatment failures rather than true recurrences. GASTROINTESTINAL ENDOSCOPY
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Follow-up phase The main goal of this study was to evaluate the long-term recurrence rate of the stenoses after stent removal. At a median follow-up of 9.1 years (2-180 months), restenosis developed in 9 of 44 patients (20%). In all cases, restenosis occurred a relatively short time after stent removal: restenosis was diagnosed after 6 months follow-up in only 1 patient, and all cases occurred within 2 years of stent removal. The endoscopic treatment protocol of Dumonceau et al.10 was comparable with ours and they were able to remove the stents in 36 patients. During a mean follow-up period of 44 months, recurrent stenoses were diagnosed in 7 patients (19%). In all but 1 patient, restenosis developed within 1 year of stent removal. The finding that restenosis occurs relatively soon after stent removal has important clinical consequences. First, it indicates that endoscopic treatment is not associated with a high rate of long-term restenosis after stent removal. Second, after stent removal rigorous follow-up of patients is necessary, especially during the first 6 to 12 months, to diagnose recurrent stenosis at an early stage. Apart from recurrent stenoses, other late complications may also occur. Four patients in the present study developed cholangitis during follow-up. In two this was due to choledocholithiasis and not recurrent stenosis. Two other patients had episodes suggestive for cholangitis but ERCP was not performed. The fact that symptoms resolved spontaneously in these patients is a point against restenosis and may suggest that these patients also had choledocholithiasis. Stone formation may be the result of biliary stasis caused by a relative stenosis. However, because all patients initially underwent biliary surgery for stone disease, the underlying stone disease may also have been responsible.14 What are the overall success and complication rates of endoscopic treatment of postoperative bile duct stenoses? The answer depends on the definitions of success and complications. In the present study, a 52% success rate can be calculated if the following patients are considered failures: patients in whom initial stent insertion was unsuccessful, patients lost to follow-up during the stent-in-situ phase and treated elsewhere without adherence to protocol, and patients with restenosis after stent removal. This is the “worst case scenario” according to the intention-to-treat principle. It can be argued that unsuccessful stent insertion in patients with a total obstruction has no adverse effect on subsequent outcome and that these patients should not be included in the inception cohort.10 Furthermore, 10 patients were lost to follow-up during the stent-insitu phase and were not treated according to proto160
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col. If these patients are arbitrarily excluded, the overall success rate increases to 75%. If the complication rates during the insertion, stent-in-situ, and follow-up phases are considered independent variables, the overall complication rate of endoscopic management is high: 72%. However, many of the complications are mild or are related to the underlying conditions (e.g., secondary biliary cirrhosis). If all patients are included, severe complications (i.e., those resulting in death or requiring surgery, admission to an intensive care unit, or prolonged hospitalization12) occurred in 18%, including 8 treatmentrelated deaths (11%). With respect to 6 deaths, however, a causal relationship with endoscopic management may be disputed: 1 patient with cholangitis had a total biliary obstruction on ERCP and refused further treatment, 2 were treated out of protocol and did not undergo stent exchange despite cholangitis, 1 died of variceal bleeding (varices and biliary cirrhosis were recognized at initial presentation), 1 died of a myocardial infarction 1 day after elective ERCP, and 1 died of multiple organ failure of unclear etiology 8 years after stent removal. If these patients are arbitrarily excluded, the rates of severe complications and related mortality are 8% and 3%, respectively. Only a few patients in the present study had proximal stenoses, which may be more difficult to treat. This may have influenced the overall results of the study. There are no prospective randomized studies comparing surgical and endoscopic treatment of postoperative biliary stenoses. A retrospective study of surgical versus endoscopic therapy has been performed.15 Both approaches had similar long-term success rates, with recurrences in 17% of patients. With no clear differences in primary outcomes between surgical and endoscopic management the choice is determined by other factors: the most important are the management of recurrent stenoses and patient preference. After Roux-en-Y hepaticojejunostomy, the biliary tree is usually not approachable endoscopically, and percutaneous transhepatic cholangiography is required for diagnosis and treatment of recurrent stenoses. Percutaneous treatment usually requires multiple sessions of balloon dilation often supplemented with long-term placement of internal-external stents. The cumulative morbidity because of bleeding and bile leakage may be as high as 40%.16 Repeated surgery may eventually be required in up to 20% of these patients17 and is associated with higher rates of complications and failure than primary hepaticojejunostomy.18 For patients who undergo endoscopic management, diagnosis and treatment of recurrent stenoses may be easier. With a previous sphincterotomy, diagnosis is straightforVOLUME 54, NO. 2, 2001
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ward. Furthermore, restenosis after endoscopic treatment develops relatively early after stent removal (<1-2 years), whereas with surgery restenosis may develop more than 10 years later.18 Prior endoscopic treatment does not preclude surgery, whereas endoscopic treatment is impossible once a Roux-en-Y loop has been constructed. Moreover, recurrent stenoses can also be successfully treated by repeated stent insertion. Although the endoscopic approach requires multiple ERCPs, most of our patients and referring physicians prefer endoscopic treatment to surgery. Therefore, it is our belief that surgery should be reserved for patients in whom endoscopic therapy is unsuccessful or patients who prefer surgical treatment. Many questions remain as to optimal endoscopic management of patients with postoperative biliary stenoses. Should stent placement always be preceded by balloon dilation? How many stents should be inserted? What is the optimal period of stent placement? In some centers, patients are treated for relatively short periods of time (e.g., 6 months) before a decision is made regarding success or failure. In other cases, stents are left in situ for extended periods, and an attempt is made to insert as many stents as possible to obtain maximum dilation of the stenosis. Using this aggressive approach, Costamagna et al.13 treated 42 patients. These investigators inserted as many stents as possible according to the diameter of the duct distal to the stenosis. Endoscopic treatment was discontinued only if the stricture was considered to be adequately dilated on fluoroscopy. Patients received a mean number of 3.2 stents (range 1-6) for a mean duration of 12 months. All stenoses resolved and none of the 42 patients developed restenosis during a median follow-up of 29 months. These impressive results suggest that a more prolonged and aggressive endoscopic approach may be justified in more difficult cases. Which subset of patients will most likely benefit from endoscopic management? There is an impression that patients in whom a stenosis is diagnosed relatively soon after surgery have a better prognosis than those who present a long time after surgery, but this has not been substantiated in follow-up studies. Stenosis in the more proximal segments of the biliary system are more difficult to treat, and primary surgical treatment has been advised for patients with hilar stenoses. In the present study the number of patients with restenosis was too small to correlate bile duct segment as a risk factor with restenosis. Multivariate analysis of large cohorts of patients will be necessary to resolve these issues.
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REFERENCES 1. The Southern Surgeons Club. A prospective analysis of 1518 laparoscopic cholecystectomies. N Eng J Med 1991;324:1073-8. 2. Deziel DJ, Millikan KW, Economou SG, Doolas A, Ko ST, Airan MC. Complications of laparoscopic cholecystectomy: a national survey of 4292 hospitals and an analysis of 77,604 cases. Am J Surg 1993;165:9-14. 3. Bergman JJ, van den Brink GR, Rauws EA, de Wit L, Obertop H, Huibregtse K, et al. Treatment of bile duct lesions after laparoscopic cholecystectomy. Gut 1996;38:141-7. 4. Nealon WH, Urrutia F. Long-term follow-up after bilioenteric anastomosis for benign bile duct stricture. Ann Surg 1996; 223:639-45. 5. Raute M, Podlech P, Jaschke W, Manegold BC, Trede M, Chir B. Management of bile duct injuries and strictures following cholecystectomy. World J Surg 1993;17:553-62. 6. Chapman WC, Halevy A, Blumgart LH, Benjamin IS. Postcholecystectomy bile duct strictures. Management and outcome in 130 patients. Arch Surg 1995;130:597-602. 7. Huibregtse K, Katon RM, Tytgat GN. Endoscopic treatment of postoperative biliary strictures. Endoscopy 1986;18:133-7. 8. Berkelhammer C, Kortan P, Haber GB. Endoscopic biliary prostheses as treatment for benign postoperative bile duct strictures. Gastrointest Endosc 1989;35:95-101. 9. Cunningham JT, Draganov PV, Rawls E, Hoffman BJ, Marsh WH, Cotton PB. Long term outcomes in patients with benign biliary stricture treated endoscopically with multiple stents [abstract]. Gastrointest Endosc 1998;47:AB112. 10. Dumonceau JM, Deviere J, Delhaye M, Baize M, Cremer M. Plastic and metal stents for postoperative benign bile duct strictures: the best and the worst. Gastrointest Endosc 1998; 47:8-17. 11. Davids PH, Rauws EA, Coene PP, Tytgat GN, Huibregtse K. Endoscopic stenting for post-operative biliary strictures. Gastrointest Endosc 1992;38:12-8. 12. Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383-93. 13. Costamagna G, Mutignani M, Perri V, Pandolfi M, Spada C, Crucitti F. Endoscopic treatment of post-operative biliary strictures: medium term results of an “aggressive” approach [abstract]. Gastroenterology 1998;103:A519. 14. Bergman JJ, van der Mey S, Rauws EA, Tijssen JG, Gouma DJ, Tytgat GN, et al. Long-term follow-up after endoscopic sphincterotomy for bile duct stones in patients younger than 60 years of age. Gastrointest Endosc 1996;44:643-9. 15. Davids PH, Tanka AK, Rauws EA, van Gulik TM, van Leeuwen DJ, de Wit LT, et al. Benign biliary strictures. Surgery or endoscopy? Ann Surg 1993;217:237-43. 16. Jan YY, Chen MF, Hung CF. Balloon dilatation of intrahepatic duct and biliary-enteric anastomosis strictures. Long term results. Int Surg 1994;79:103-5. 17. Vos PM, van Beek EJ, Smits NJ, Rauws EA, Gouma DJ, Reeders JW. Percutaneous balloon dilatation for benign hepaticojejunostomy strictures. Abdom Imaging 2000;25: 134-8. 18. Pitt HA, Miyamoto T, Parapatis SK, Tompkins RK, Longmire WP Jr. Factors influencing outcome in patients with postoperative biliary strictures. Am J Surg 1982;144:14-21. 19. Bismuth H. Postoperative strictures of the bile duct. In: Blumgarth LH, editor. The biliary tract. Edinburgh: Churchill Livingstone; 1982. p. 209-18.
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Background: The outcome of temporary biliary stent placement for postoperative bile duct stenosis was retrospectively evaluated with the main aim of assessing long-term complications after stent removal. Methods: ERCP was performed between 1981 and 1991 in 74 patients with postoperative bile duct stenoses. Two 10F stents were inserted for a maximum of 12 months with stent exchange every 3 months to avoid cholangitis caused by clogging. Results: Stent insertion failed in 11 patients with complete and 4 patients with incomplete biliary obstruction. Early complications occurred in 14 patients (19%) including 2 deaths. Therefore 57 patients were included in the stent phase of the study. In 10 patients the referring physician did not adhere to the treatment protocol, and nonelective stent exchange for jaundice and/or cholangitis was necessary in 7 (70%). Of the 47 patients treated according to protocol, complications developed in 40% during the period with stents in situ. Stents were eventually removed in 44 patients who were subsequently followed for a median of 9.1 years. Late complications developed in 15 patients (34%) including recurrent stenosis in 9 (20%). All cases of recurrent stenosis occurred within 2 years of stent removal. Conclusions: Endoscopic treatment is feasible in 80% of patients who undergo an ERCP for postoperative bile duct stenosis. After stent insertion and during the time with stents in situ, complications occur at a significant rate but are usually mild or reflect the patient’s underlying condition. After stent removal, recurrent stenosis develops in 20% of patients within 2 years of stent removal. Endoscopic treatment should be the initial management of choice for postoperative bile duct stenosis. (Gastrointest Endosc 2001;54:154-61.)
Postoperative bile duct injuries occur in 0.2% to 0.5% of patients undergoing open cholecystectomy and in 0% to 2.7% after laparoscopic cholecystectomy.1,2 Four types of surgical bile duct injury can be identified3: type A, leakage from minor bile ducts (cystic duct or peripheral hepatic radicles); type B, leakage from major bile ducts (common bile duct, common hepatic duct, left or right main hepatic ducts); type C, bile duct stenoses without bile leakage; and type D, complete transection of the duct with or without excision of some portion of the biliary tree. Minor and major bile duct leaks are best treated endoscopically with temporary placement of biliary Received June 29, 2000. For revision September 5, 2000. Accepted April 13, 2001. From the Department of Gastroenterology and Hepatology and the Department of Surgery, Academic Medical Center, University of Amsterdam, The Netherlands. Presented in part at the annual meeting of the American Society for Gastrointestinal Endoscopy, May 16-19, 1999, Orlando, Florida (Gastrointest Endosc 1999;49:AB178). Reprint requests: J.J.G.H.M. Bergman, MD, Department of Gastroenterology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Copyright © 2001 by the American Society for Gastrointestinal Endoscopy 0016-5107/2001/$35.00 + 0 37/1/116455 doi:10.1067/mge.2001.116455 154
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stents and/or endoscopic sphincterotomy, whereas surgical treatment is required in all patients with complete ductal transections (type D lesions).3 For patients with postoperative bile duct stenosis (type C lesions, Fig. 1), the choice between endoscopic or surgical management is less clear. Traditionally, these lesions have been treated with reconstructive surgery (mainly hepaticojejunostomy).4-6 However, over the last decade there have been many efforts to explore endoscopic management.7-10 Endoscopic treatment usually involves temporary placement of 1 or more stents through the stenosis to achieve gradual and permanent dilation of the fibrotic tissue in the strictured segment. Stents are usually kept in situ for up to 1 year with trimonthly exchange to prevent cholangitis. The premise of endoscopic treatment is that once the stenosis is adequately dilated, the fibrotic tissue will undergo remodeling thereby preventing elastic recoil and recurrence of the stenosis after removal of the stents. Published experience with this form of endoscopic management has been favorable, but all studies refer only to early results. The most important criticism of endoscopic management relates to the unknown, long-term outcome of these patients. It is claimed that many stenoses will eventually recur VOLUME 54, NO. 2, 2001
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A
B
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C
D
Figure 1. Retrograde cholangiograms in patient with subhilar bile duct stenosis after laparoscopic cholecystectomy. There is gradual disappearance of the stenosis during stent therapy. A, Cholangiogram before treatment. B, After 3 months with stent in situ. C, After 6 months with stent in situ. D, After 12 months with stent in situ: the stenosis has been dilated adequately.
and that surgery will be required at a later time under less favorable conditions (older age, secondary biliary cirrhosis, and secondary changes in the biliary system caused by the long-term presence of the stents). Therefore a long-term follow-up study was performed in all patients who were treated by temporary biliary stent placement for postoperative bile duct stenoses between 1981 and 1991. PATIENTS AND METHODS All patients who underwent ERCP between January 1981 and January 1991 for diagnosis and management of postoperative bile duct stenosis were included. Bile duct stenosis was defined as a luminal narrowing of the bile duct with proximal dilation demonstrated by cholangiography.10 Patients were only included if they had symptoms (jaundice, cholangitis) or signs (progressive cholestatic liver function tests) of biliary obstruction before the ERCP. Patients with malignant stenoses or benign stenoses caused by chronic pancreatitis, primary sclerosing cholangitis, or choledocholithiasis were excluded. Also excluded were patients with postsphincterotomy stenoses or biliodigestive anastomoses. A total of 74 patients fulfilled these selection criteria. This cohort of patients has been previously described.11 In the present study 6 patients were excluded from the cohort: 5 with stenoses of biliodigestive anastomoses and 1 who in retrospect most likely had a malignant biliary stenosis. Treatment protocol After obtaining a diagnostic cholangiogram and documentation of the site and extent of the stenosis, attempts were made to pass a hydrophilic guidewire and diagnostic VOLUME 54, NO. 2, 2001
PHASE: Stent Insertion
.................................................................................................................................................................................................................. Referred for ERCP N=74 Failed stent insertion (n=15) total stop (n=11), no passage of guide wire (n=3), restlessness (n=1)
Complications (n=14, 19%) Failed ERCP, cholangitis, death (n=1) Pancreatitis, death (n=1) Cholangitis (n=6) Bleeding (n=4) Pancreatitis (n=2)
Stent insertion successful N=59 Early death (n=1) Surgery, patient preference (n=1)
Stent in situ
Stent in situ phase .................................................................................................................................................................................................................. N=57 Complications (n=7, 70%) Cholangitis and/or jaundice, No adherence to protocol, stent exchange (n=5) treated elsewhere (n=10) Cholangitis, death (n=2) Stent in situ phase, treated according to protocol N=47 Complications (n=19, 40%) Fever after elective ERCP (n=7) Cholangitis, stent exchange (n=5) Cholestasis, stent exchange (n=5) Stent migration, surgery (n=2) Follow-up Stents removed .................................................................................................................................................................................................................. N=44 Restenosis (n=9) Surgery (n=4) Repeated stenting (n=5) Unrelated deaths (n=2) Stent migration, surgery (n=1)
Other complications: (n=6) Cholangitis, ERCP stones (n=2) Cholangitis, no ERCP (n=1) Fever of unknown cause (n=1) Variceal bleeding, death (n=1) Transient pain & cholestasis (n=1)
Median follow-up: 9.1 years (2 mo-15yrs)
Deaths: (n=16) Variceal bleeding (n=2) Cardiac infarction post-ERCP (n=1) Multiorgan failure eci (n=1) Unrelated (n=12)
Figure 2. Flow diagram of outcomes of endoscopic management in 74 patients with postoperative bile duct stenosis. catheter through the stenosis. If the stenosis was too tight to allow passage of the catheter, dilating catheters of gradually increasing diameter (2-3 mm outside diameter) were passed over the guidewire and through the stenosis, sometimes with supplemental balloon dilatation. There was no GASTROINTESTINAL ENDOSCOPY
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Table 1. Baseline characteristics of patients N = 74 (%) Presenting symptoms Jaundice Cholangitis Cholestatic liver function tests Bile leakage/abnormal T-tube cholangiography Unknown Surgical history* Cholecystectomy ± common bile duct exploration, single operation Cholecystectomy ± common bile duct exploration, direct injury repair Cholecystectomy, repeated common bile duct exploration Unknown† Localization of the stenosis (Bismuth19) Common bile duct Within 2 cm distal from bifurcation Bifurcation Hepatic ducts Right hepatic duct Concomitant bile leakage Bile duct stones
33 20 12 7 2
(45) (27) (16) (9) (3)
48 (65) 15 (20) 9 (12) 2 (3) 39 29 3 1 2 14 17
(53) (39) (4) (1) (3) (19) (23)
*No laparoscopic procedure were performed in the cohort of patients (1981-1991). †Type of biliary surgery performed in these patients could not be determined.
standardized protocol concerning balloon dilation or catheter dilation before stent placement. An Amsterdamtype straight polyethylene stent was then inserted over the guidewire and catheter, thus bridging the stenosis. The treatment protocol specified placement of two 10F stents if possible. For multiple stent insertion, an endoscopic sphincterotomy was performed to facilitate stent placement. With tight stenoses sometimes only a 7F or a single 10F stent could be placed. In such cases, the single stent was exchanged for two 10F stents after 6 weeks, and then the 2 stents were subsequently exchanged every 3 months to avoid cholangitis caused by clogging. The maximum treatment period with 2 stents in situ was 12 months. The stents were not replaced if the stenosis was considered to be adequately dilated based on the following criteria as subjectively assessed by the endoscopist: (1) adequate dilation of the stenosis on cholangiography, (2) satisfactory drainage of contrast from the biliary tree, (3) passage of a diagnostic catheter and extraction balloon through the stenosis without encountering significant resistance. Before ERCP, all patients were treated prophylactically by intravenous administration of antibiotics (amoxicillin and gentamycin). In the absence of cholangitis as an indication for the ERCP, no antibiotics were given after the procedure. Informed consent was obtained from all patients. Outcome parameters and sources of information Three different treatment phases were defined retrospectively: (1) stent insertion phase: period between first attempt at stent placement and discharge from the hospital, (2) stent in situ phase: period during which stents 156
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remained in situ including stent exchange every 3 months, and (3) follow-up phase: period between final removal of the stents and end of follow-up. Complications were noted and graded as to severity according to 1991 consensus guidelines.12 Information concerning the stent insertion and stent in situ phases was obtained from our endoscopy reports and medical records at referring hospitals. Because follow-up after stent removal comprised a period up to 15 years, information pertinent to the follow-up phase was obtained from multiple sources to ensure that data collection was complete. First, the primary care physicians for all patients were contacted by telephone and were asked to check the patients’ files for any medical problems since stent removal. Second, all patients alive at the point of data collection were contacted by telephone and asked about any medical problems since removal of the stents. Subsequently these patients were asked to complete a postal questionnaire that inquired about recurrence of biliary symptoms and related diagnostic or therapeutic interventions. Patients who did not respond were recontacted by telephone. Third, all patients were invited to have a blood sample taken for the following liver function tests: bilirubin (conjugated and deconjugated), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transferase. Again, those who did not respond were contacted by telephone. If the patient had died, the primary care physician and the patient’s family were contacted to determine the cause of death and medical history after stent removal. If one or more of the above-mentioned sources of information suggested that biliary-related complications had occurred, the attending physician was contacted and the medical records at the local hospital were inspected. If a questionnaire and/or liver function tests indicated the possibility of biliary pathology, the patient was invited to undergo further diagnostic testing. Predictors of restenosis during follow-up Univariate and multivariate analyses were performed to determine whether there were any patient characteristics that could predict the occurrence of restenosis during follow-up. The following potential factors were evaluated: age, gender, time interval between surgery and diagnosis of the stenosis, anatomic location of the stenosis, presence of bile leakage, and the number of ERCPs required to achieve initial stent placement.
RESULTS Patient characteristics ERCP with stent insertion was attempted in 74 patients (33 men, 41 women; median age 62 years, range 19-84 years; Fig. 2). Patients either had symptoms at presentation or had evidence of progressive cholestasis after recent hepatobiliary surgery with peroperative repair of an injury to the biliary tree (Table 1). Presenting symptoms, prior surgical history, and diagnostic findings at ERCP are shown in Table 1. VOLUME 54, NO. 2, 2001
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Stent insertion phase A diagnostic cholangiogram was obtained in all patients (Table 1, Fig. 2). Stent insertion was successful in 59 patients (80%) after a mean of 1.4 procedures (range 1-7). In 2 patients a rendezvous procedure after percutaneous transhepatic cholangiography was necessary for successful endoscopic stent placement. Reasons for unsuccessful stent insertion were as follows: total obstruction in the bile duct (n = 11), successful proximal cholangiography but inability to pass a guidewire through stenosis (n = 3), and patient restlessness during ERCP (n = 1). Details concerning further management and early complications in these patients are given in Table 2. Patients in whom stent insertion was unsuccessful are only considered in the analysis of early complications of ERCP. Early complications occurred in 14 patients (19%): fever/cholangitis (n = 7), postsphincterotomy bleeding (n = 4), and pancreatitis (n = 3). Two patients died shortly after ERCP. The first was an 82-year old woman in whom stent insertion was unsuccessful because of total biliary obstruction. She refused further treatment and died of ongoing cholangitis and sepsis 10 days after the ERCP. The second patient died of a cerebral infarction during intensive treatment for a severe pancreatitis. All other early complications were graded as mild. Stent-in-situ phase Of the 59 patients in whom stent insertion was initially successful, 1 died of a severe pancreatitis (see previous section) and 1 preferred to undergo elective hepaticojejunostomy. A total of 57 patients therefore entered the stent-in-situ phase (Fig. 2). Forty-eight patients received 2 stents; 9 had only 1 stent inserted. Ten patients were lost to follow-up during the stent-in-situ phase. For these patients the referring physician did not adhere to the treatment protocol and further management was not carried out in our unit. Outcomes for these patients were determined retrospectively. The further management of these patients, who were generally elderly and had significant comorbid conditions, was highly variable and mainly triggered by signs of stent dysfunction. Seven patients (70%) underwent 1 or more stent exchange procedures (range 1-14) after developing jaundice and/or cholangitis. Nine died during follow-up with stents in situ. In 2 patients death was due to cholangitis secondary to stent dysfunction. Two patients did not develop any complications and died of unrelated causes. One patient was alive at the time of follow-up. Eventually she had her stents removed after 3 episodes of stent therapy. Compared with the other 47 patients who entered the stent-in-situ phase, the VOLUME 54, NO. 2, 2001
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Table 2. Further management and outcome for 15 patients with postoperative bile duct stenosis in whom stent insertion was unsuccessful N = 15 Expectant management Died of ongoing cholangitis No problems during follow-up Hepaticojejunostomy Bile leakage Bleeding/sepsis Pulmonary embolism
2 1 1 13 1 1 1
Total cohort comprised 74 patients.
10 lost to follow-up during this phase had a higher median age (79 years vs. 58 years; p < 0.00l MannWhitney test). There were no significant differences with respect to location and extent of the stenoses. Of the 47 patients who completed the stent-in-situ phase according to protocol, 19 (40%) experienced complications while the stents were in place (Fig. 2). In 10 patients nonelective stent exchange was necessary because of jaundice or cholestatic lever function tests (n = 6), or cholangitis (n = 4). After stent exchange, symptoms resolved and the complication was graded mild in all cases. Seven patients developed fever after an elective stent exchange and were treated with antibiotics. Two severe complications were encountered during the stent-in-situ phase for which surgery was eventually required. In 1 patient a stent had migrated into the duodenum and could not be retrieved endoscopically. He underwent laparotomy for stent removal but continued to undergo endoscopic treatment according to protocol. In the second patient the stent had migrated into the bile duct and could not be retrieved during ERCP. This patient underwent elective surgery with stent removal and hepaticojejunostomy. Two patients died during the stent-in-situ phase of unrelated causes. Follow-up phase Forty-four patients (20 men, 24 women, median age 57 years, range 19-83 years) completed the stent-in-situ phase according to protocol and eventually had their stents removed (Fig. 2). All patients or relatives were contacted in addition to 96% of their primary care physicians. Of the patients alive at the time of data collection, 86% completed the questionnaire and 93% had a blood sample taken. The median period of follow-up in these 44 patients was 9.1 years (range 2 months-15 years). Fifteen patients (34%) developed complications during follow-up (Fig. 2). Stenosis recurred in 9 patients at a median of 2.6 months (range 1 week-2 years) after stent removal. Presenting symptoms were as follows: cholangitis (n GASTROINTESTINAL ENDOSCOPY
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Table 3. Further management in 9 of 44 patients with postoperative bile duct stenoses that recurred after temporary placement of biliary endoprostheses N=9 Reconstructive surgery Hepaticojejunostomy* Choledochoduodenostomy† Repeated stent therapy Unsuccessful stent therapy: hepaticojejunostomy‡ Stented until unrelated death Stented, died of myocardial infarction after ERCP Repeated stent therapy (3 times)‡
Figure 3. Kaplan-Meier plot showing proportion of patients without signs of restenosis among 44 patients with postoperative biliary stenosis who underwent stent placement and eventually had their stents removed.
= 6), upper abdominal pain and cholestasis (n = 2), and jaundice (n = 1). Symptoms were graded mild in all cases. ERCP demonstrated recurrence of the original stenosis in all 9 patients with proximal bile duct stones in 2. A Kaplan-Meier plot showing the proportion of patients without signs of restenosis is shown in Figure 3. Of the patients with recurrent stenosis, all but one presented within the first 6 months after stent removal. In patients followed more than 2 years, no cases of restenosis were found. The preferred treatment of recurrent stenoses was surgical reconstruction. Some patients, however, refused surgery or were considered extremely poor candidates and were thus again treated endoscopically. The management and longterm outcomes of the 9 patients who developed recurrent stenoses are summarized in Table 3. Apart from the 9 patients with symptoms related to recurrent stenosis, 6 developed other complications during follow-up. Two underwent ERCP for removal of bile duct stones. At ERCP there was no evidence of restenosis. After stone removal these 2 patients were followed for 2 and 13 years, respectively, during which time there were no further complications. Fever developed in one patient and he had cholestatic liver function tests 1 year after removal of the stents. ERCP was not performed because symptoms resolved spontaneously. This patient was followed for 9 years, during which time there were no further complications, and he died of an unrelated cause. The complications in these 3 patients were graded as mild. Another patient was hospitalized 6 years after stent removal because of 158
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4 3 1 5 2 1 1 1
*One patient with 6 years of event-free follow-up; 1 patient with 4 episodes of cholangitis in the first 2 years followed by event-free follow-up until unrelated death after 11 years; 1 patient with secondary biliary cirrhosis diagnosed at the time of surgery who died of variceal bleeding 4 years after surgery. †Six years after surgery 1 episode of jaundice caused by ductal stones, removed at ERCP. ‡No complications since last intervention (event-free follow-up >3 years in all).
fever, and a lesion was found by US in the liver. USguided aspiration was performed twice and yielded no pus, and cultures remained negative. The fever resolved spontaneously and there were no problems during a further 4 years of follow-up. This complication was graded as moderate. An 80-year-old man was hospitalized 7 years after stent removal because of abdominal pain and cholestatic liver function tests. The symptoms resolved spontaneously and, because of the overall poor condition of the patient, an expectant treatment policy was adopted. A year later he died of shock and multi-organ failure without a clearly defined cause. This complication was graded as severe and most likely biliary in origin. Last, a patient with secondary biliary cirrhosis and varices at the time of initial stent insertion died 10 years after stent removal because of variceal bleeding. Several ERCPs were performed to check for restenosis, but the bile duct was found to be patent on all occasions. This complication was graded as severe and related to the underlying disease. Deaths during follow-up phase Sixteen of the 44 patients (36%) died during follow-up (Fig. 2); 4 deaths (9%) were biliary related. The first patient died of shock and multi-organ failure 1 year after a period during which he had abdominal pain and cholestatic liver function tests (see previous section). Two patients died as a result of variceal bleeding caused by liver cirrhosis. In 1 of these patients biliary cirrhosis was present when the stenosis was diagnosed (see previous section); in the second patient it was diagnosed at the time of reconVOLUME 54, NO. 2, 2001
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structive surgery for restenosis. One patient died of a myocardial infarction 1 day after an elective ERCP for stent exchange. In this patient the stenosis had recurred at 2 months after stent removal. He refused surgery and was treated endoscopically with stent insertion and exchange every 3 months. Questionnaires and liver function tests Of the 28 patients alive at the time of follow-up, 24 (86%) returned the questionnaire and none reported any biliary-related symptoms. Blood samples were obtained in 26 patients (93%) and mild cholestatic liver function tests (<3 times upper limit of normal) were found in 4. In 1 patient these abnormalities were due to biliary cirrhosis that had been diagnosed before the initial diagnosis of biliary stenosis. In another patient the liver function abnormalities were stable and due to atrophy of 2 segments of the right liver lobe that in retrospect were never drained endoscopically. The third patient with mild cholestatic liver function tests underwent magnetic resonance cholangiopancreatography that demonstrated no evidence of recurrent stenosis. The fourth patient, who lived abroad, refused further evaluation. Predictors of restenosis during follow-up To determine whether there were any patient characteristics that predicted restenosis during follow-up, the following factors were tested in univariate and multivariate models: age, gender, time interval between initial surgery and diagnosis of the stenosis, anatomic location of the stenosis, presence of bile leakage, and the number of ERCPs required for initial stent placement. None of these were statistically significant. DISCUSSION The endoscopic management of postoperative biliary stenosis currently involves stent placement, usually two, followed by stent exchange every 3 months for a maximum treatment period of 12 months.7,8-10 Treatment divides into 3 phases: stent insertion, stent-in-situ (including trimonthly stent exchange), and follow-up after stent removal. Stent insertion phase Endoscopic treatment of total ductal obstruction is not possible. Because ERCP is required for diagnosis, treatment of these patients is regarded as unsuccessful. In a strict sense, these patients do not have a true stenosis. Other studies have therefore included only patients with incomplete ductal stenosis.10,13 Dumonceau et al.10 successfully inserted stents in 47 of 48 patients (98%) with incomplete postoperative bile duct stenoses, a rate comparable VOLUME 54, NO. 2, 2001
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with the 94% in our study. Early complications of the stent insertion phase are mainly sphincterotomyrelated or are a reflection of the pretreatment condition of the patient (e.g., fever associated with bile leakage). Early complications developed in 19% of our patients. Dumonceau et al.10 encountered early complications in 6 of 48 patients (12.5%), whereas Costamagna et al.13 observed 4 complications in 42 patients (9.5%) who had stents placed for postoperative biliary stenoses. The present study focused on long-term outcome for patients who underwent endoscopic treatment 10 to 15 years earlier. Therefore, the relatively high early complication rate of 19% may not reflect current endoscopic practice. Stent-in-situ phase Because stents were in situ for a period of up to 1 year, complications were relatively common: 40% of patients had 1 or more complications during the stentin-situ period. Fever after elective stent exchange, in all cases effectively managed conservatively with antibiotics, and symptoms caused by stent dysfunction accounted for the majority of these complications. Stent dysfunction mainly occurred in patients whose referring physicians did not adhere to the protocol for elective stent exchange every 3 months. The present study includes patients who were treated when endoscopic management of postoperative bile duct stenosis was in the early stages of development. Since then, endoscopic treatment of these patients has become more established. Currently, when ERCP is electively performed at 3-month intervals, complications caused by stent dysfunction are mild and occur in 10% to 15% of patients over the 1 year during which stents remain in situ.13 Ten patients in the stent-in-situ phase of treatment were often lost to follow-up because of a failure to adhere to the treatment protocol. Only in retrospect was the overall poor outcome of these patients established: 70% developed complications during the in situ phase and in 2 patients death was due to cholangitis resulting from stent dysfunction. Although selection bias on the part of attending physicians cannot be excluded (patients lost to follow-up were significantly older than patients who completed the treatment protocol), the poor outcome in these patients underscores the need for strict adherence to the treatment protocol. In the present study, all patients who were treated according to protocol eventually had their stents removed, whereas Dumonceau et al.10 were able to remove the stents in 95% of their patients. However, some of the instances of stricture recurrence in both studies occurred shortly after stent removal and these cases might be considered treatment failures rather than true recurrences. GASTROINTESTINAL ENDOSCOPY
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Follow-up phase The main goal of this study was to evaluate the long-term recurrence rate of the stenoses after stent removal. At a median follow-up of 9.1 years (2-180 months), restenosis developed in 9 of 44 patients (20%). In all cases, restenosis occurred a relatively short time after stent removal: restenosis was diagnosed after 6 months follow-up in only 1 patient, and all cases occurred within 2 years of stent removal. The endoscopic treatment protocol of Dumonceau et al.10 was comparable with ours and they were able to remove the stents in 36 patients. During a mean follow-up period of 44 months, recurrent stenoses were diagnosed in 7 patients (19%). In all but 1 patient, restenosis developed within 1 year of stent removal. The finding that restenosis occurs relatively soon after stent removal has important clinical consequences. First, it indicates that endoscopic treatment is not associated with a high rate of long-term restenosis after stent removal. Second, after stent removal rigorous follow-up of patients is necessary, especially during the first 6 to 12 months, to diagnose recurrent stenosis at an early stage. Apart from recurrent stenoses, other late complications may also occur. Four patients in the present study developed cholangitis during follow-up. In two this was due to choledocholithiasis and not recurrent stenosis. Two other patients had episodes suggestive for cholangitis but ERCP was not performed. The fact that symptoms resolved spontaneously in these patients is a point against restenosis and may suggest that these patients also had choledocholithiasis. Stone formation may be the result of biliary stasis caused by a relative stenosis. However, because all patients initially underwent biliary surgery for stone disease, the underlying stone disease may also have been responsible.14 What are the overall success and complication rates of endoscopic treatment of postoperative bile duct stenoses? The answer depends on the definitions of success and complications. In the present study, a 52% success rate can be calculated if the following patients are considered failures: patients in whom initial stent insertion was unsuccessful, patients lost to follow-up during the stent-in-situ phase and treated elsewhere without adherence to protocol, and patients with restenosis after stent removal. This is the “worst case scenario” according to the intention-to-treat principle. It can be argued that unsuccessful stent insertion in patients with a total obstruction has no adverse effect on subsequent outcome and that these patients should not be included in the inception cohort.10 Furthermore, 10 patients were lost to follow-up during the stent-insitu phase and were not treated according to proto160
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col. If these patients are arbitrarily excluded, the overall success rate increases to 75%. If the complication rates during the insertion, stent-in-situ, and follow-up phases are considered independent variables, the overall complication rate of endoscopic management is high: 72%. However, many of the complications are mild or are related to the underlying conditions (e.g., secondary biliary cirrhosis). If all patients are included, severe complications (i.e., those resulting in death or requiring surgery, admission to an intensive care unit, or prolonged hospitalization12) occurred in 18%, including 8 treatmentrelated deaths (11%). With respect to 6 deaths, however, a causal relationship with endoscopic management may be disputed: 1 patient with cholangitis had a total biliary obstruction on ERCP and refused further treatment, 2 were treated out of protocol and did not undergo stent exchange despite cholangitis, 1 died of variceal bleeding (varices and biliary cirrhosis were recognized at initial presentation), 1 died of a myocardial infarction 1 day after elective ERCP, and 1 died of multiple organ failure of unclear etiology 8 years after stent removal. If these patients are arbitrarily excluded, the rates of severe complications and related mortality are 8% and 3%, respectively. Only a few patients in the present study had proximal stenoses, which may be more difficult to treat. This may have influenced the overall results of the study. There are no prospective randomized studies comparing surgical and endoscopic treatment of postoperative biliary stenoses. A retrospective study of surgical versus endoscopic therapy has been performed.15 Both approaches had similar long-term success rates, with recurrences in 17% of patients. With no clear differences in primary outcomes between surgical and endoscopic management the choice is determined by other factors: the most important are the management of recurrent stenoses and patient preference. After Roux-en-Y hepaticojejunostomy, the biliary tree is usually not approachable endoscopically, and percutaneous transhepatic cholangiography is required for diagnosis and treatment of recurrent stenoses. Percutaneous treatment usually requires multiple sessions of balloon dilation often supplemented with long-term placement of internal-external stents. The cumulative morbidity because of bleeding and bile leakage may be as high as 40%.16 Repeated surgery may eventually be required in up to 20% of these patients17 and is associated with higher rates of complications and failure than primary hepaticojejunostomy.18 For patients who undergo endoscopic management, diagnosis and treatment of recurrent stenoses may be easier. With a previous sphincterotomy, diagnosis is straightforVOLUME 54, NO. 2, 2001
Follow-up after biliary stent placement for postoperative bile duct stenoses
ward. Furthermore, restenosis after endoscopic treatment develops relatively early after stent removal (<1-2 years), whereas with surgery restenosis may develop more than 10 years later.18 Prior endoscopic treatment does not preclude surgery, whereas endoscopic treatment is impossible once a Roux-en-Y loop has been constructed. Moreover, recurrent stenoses can also be successfully treated by repeated stent insertion. Although the endoscopic approach requires multiple ERCPs, most of our patients and referring physicians prefer endoscopic treatment to surgery. Therefore, it is our belief that surgery should be reserved for patients in whom endoscopic therapy is unsuccessful or patients who prefer surgical treatment. Many questions remain as to optimal endoscopic management of patients with postoperative biliary stenoses. Should stent placement always be preceded by balloon dilation? How many stents should be inserted? What is the optimal period of stent placement? In some centers, patients are treated for relatively short periods of time (e.g., 6 months) before a decision is made regarding success or failure. In other cases, stents are left in situ for extended periods, and an attempt is made to insert as many stents as possible to obtain maximum dilation of the stenosis. Using this aggressive approach, Costamagna et al.13 treated 42 patients. These investigators inserted as many stents as possible according to the diameter of the duct distal to the stenosis. Endoscopic treatment was discontinued only if the stricture was considered to be adequately dilated on fluoroscopy. Patients received a mean number of 3.2 stents (range 1-6) for a mean duration of 12 months. All stenoses resolved and none of the 42 patients developed restenosis during a median follow-up of 29 months. These impressive results suggest that a more prolonged and aggressive endoscopic approach may be justified in more difficult cases. Which subset of patients will most likely benefit from endoscopic management? There is an impression that patients in whom a stenosis is diagnosed relatively soon after surgery have a better prognosis than those who present a long time after surgery, but this has not been substantiated in follow-up studies. Stenosis in the more proximal segments of the biliary system are more difficult to treat, and primary surgical treatment has been advised for patients with hilar stenoses. In the present study the number of patients with restenosis was too small to correlate bile duct segment as a risk factor with restenosis. Multivariate analysis of large cohorts of patients will be necessary to resolve these issues.
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