Endoscopic Treatment of Anastomotic Biliary Stenosis in Patients With Orthotopic Liver Transplantation

The choledocho-choledochostomy stricture is one of the most frequent complications occurring after liver transplantation. Today endoscopic retrograde cholangiopancreatography may be considered one of the most common methodologic approaches for the diagnosis; at the same time it provides an effective treatment of the stenosis, avoiding more invasive surgery. Biliary flow through a strictured anastomosis definitely improves after endoscopic stenting which, in most cases, resolves the biliary obstruction syndrome; moreover, the stent could allow restoration of the anatomical and functional integrity of the common bile duct. We have successfully treated eight liver transplanted patients with biliary anastomotic stenosis by endoscopic stenting of the common bile duct or by balloon dilation (one patient). The stents were replaced every 3 to 4 months and then removed after 1 year of follow-up. We observed one patient with acute cholangitis due to the clogging of the prosthetic device.

A clinically significant stenosis results in a corresponding biliary obstruction syndrome (BOS), which can be detected by specific laboratory findings. In some OLTX patients morphological evidence for a dilated biliary tree above the stenosis may be lacking. In addition, dilation of the recipient common bile duct may be found (1). Endoscopic retrograde cholangiopancreatography (ERCP) is a commonly used method for morphological and functional evaluation of the biliary ducts after liver transplantation (6,8). In addition, it could provide less invasive treatment of stenosis characterized by impairment of the bile flow.
The aim of our study was to verify the possible therapeutic role of biliary operative endoscopy in OLTX patients with CCS stenosis.

METHODS AND PATIENTS
Ten of 160 patients with OLTX (6.25%) underwent ERCP because of BOS (Figs. to 4) with or without evidentjaundice. Etiological and biological features of patients are shown in Table 1. Serum bilirubin levels ranged from 2.10 to 13.50 mg/dl (mean value 4.61 mg/dl). Stenosis of the end-to-end CCS was found in eight patients. Only two of them had mildly dilated biliary trees upstream. The following treatments were performed on the eight stenotic patients:   The balloon dilation and the double stent placement required previous endoscopic papillotomy. Endoscopic procedures were performed with the JF-1 T20 side-viewing duodenoscope (Olympus Corp., Lake Success, NY).
Informed consent was obtained.
The efficacy of the biliary drainage was evaluated by improvement of the BOS 7 days after the endoscopic procedure. The follow-up schedule required substitution of the stents every 3 to 4 months and definitive removal after year, unless complications occurred (Fig. 6).

RESULTS
In all cases the BOS was improved within the 7th day after stenting: jaundice disappeared in seven patients, while in one patient the bilirubin level decreased from 11.4 to 2.3 mg/dl. Table 2 summarizes what happened for each patient during the follow-up period.
Canalization of the stenotic tract was achieved for the patient treated with balloon dilation at the first attempt, and there were no recurrences (control by ERCP at 4.5 months) or complications until the end of his follow-up (9 months). Three of the six patients treated with a single OF stent finished the established program. These patients  were always symptom-free, without clinical or biohumoral evidence of BOS. One patient had acute cholangitis 20 days alter stenting; clogging, with obstruction of the stent, was found by ERCP. The obstructed device was replaced with a new one of the same size, after which the septic condition rapidly improved. The patient had acute hepatic rejection in the 3rd month of follow-up and was given another transplant. The last two patients have not yet been followed-up for more than 3 months.
The patient treated with double stenting had a replacement with a single OF stent at 4 months, then another replacement at 7 months. Finally, the stent was removed at 10 months, without any complications and the patient is now symptom-free.

DISCUSSION
The onset of evident biliary obstruction in a OLTX patient could immediately lead one to think of a possible hepatic rejection. However, in some cases it may more simply be due to a stenosis of the choledocho-choledochostomy.
Postoperative strictures in OLTX patients seem to be independent of either the most common etiopatho-96 A. ROSSI et al. Figure 5 Stenting is performed by a 10F polyethylene device (same patient as Fig. 3). Figure 6 Twelve months after the first stenting procedure: the last stent is removed and the choledocho-choledochostomy is well canalized (same patient as Fig. 3).
genetic factors connected to the hepatic disease or infectious or pharmacological situations. The main cause of this complication, apart from technical problems, is probably the unfavorable blood supply to the biliary tract. 3 ERCP is therefore an important diagnostic procedure for these patients and moreover it offers an effective and relatively noninvasive treatment of the stenosis itself.6, 2 The CCS stenosis may be classified as "not neoplastic" and, if so, it could be treated with the same endoscopic procedures that have been codified for the most classical model of "benign stenosis" of the common bile duct, that is, the postcholecystectomy stricture. 3 Following this guideline we used both balloon dilation and, above all, the polyethylene prosthesis. Stenting seems to offer better advantages, as well as a lower risk of complications. This procedure in fact enhances biliary flow so that the BOS can rapidly improve. Moreover, it may allow the common bile duct to rebuild itself around the stent, which in this way becomes a sort of plastic mold: after 10 to 12 months of stenting, the CCS could be wide enough to permit an adequate biliary flow. In our experience, at the end of follow-up schedule ERCP showed a well-canalized CCS, and patients were clinically asymptomatic. Prolonged clinical observation would be necessary to establish the long-term efficacy of this procedure.
In the majority of our patients, ERCP showed smallsized biliary trees above the stricture. This might be due to early and temporary edema and infiltration of the portal tract of the transplanted liver, although a conclusive explanation is still lacking. However, this finding should be differentiated from the so-called "vanishing bile duct syndrome". This nosological entity, recently described in the literature (14), is defined as disappearance of biliary ducts. It can be seen even histologically and may be considered a particular type of liver rejection. Arterial thrombosis is another pathogenesis to be suspected in the presence of single or multiple stenosis of bile ducts in a transplanted liver. Because of the above-mentioned small size of the common bile duct, we preferred to use single 10F stents. Only one patient was given a double 10 + 7 F stent. Nevertheless, we did not find any delay or limiting of the canalization of strictures.
Finally, we want to emphasize the need for periodically planned replacement of the stents to reduce the risk of clogging and avoid the consequent cholangitis, which is a particularly dreadful event in OLTX patients treated with immunosuppressive drugs.