Metal Stents in Common Bile Duct Strictures Secondary to Chronic Pancreatitis: a ”New” Endoscopic Treatment for an Old Problem

It has long been recognized that common bile duct (CBD) strictures can arise as a sequela of chronic pancreatitis [1]. However, until the 1970s, this type of CBD stricture was regarded as unusual or was labeled as an insidious disease, due to the difficulty of diagnosis in patients who were often alcohol abusers. In this setting, since proper imaging studies were unavailable, the onset of cholestasis was considered in most cases to be the consequence of the alcoholic damage to the liver. In the past, delayed diagnosis often led to the development of several complications of long-standing cholestasis, such as cholangitis and biliary cirrhosis. Nowadays, the dramatic improvement in pancreaticobiliary imaging modalities allows the physician to make a much earlier diagnosis.

The reported incidence of patients with CBD strictures secondary to chronic pancreatitis increased in the 1980s due to the advent of endoscopic retrograde cholangiopancreatography (ERCP). In that period, the reported average incidence of CBD strictures in association with chronic pancreatitis was about 6 %, with a broad range from 2.7 % to 45.6 % [2] [3] [4] [5] [6] [7]. The percentage of symptomatic strictures reported in the papers concerned was very high, ranging from 63 % to 100 % [4] [5] [7] [8] [9] [10] [11] [12]. This wide variation reflects bias in patient selection, differences in the population groups studied, and differences in the definition of obstruction.

With the development of therapeutic endoscopy in the pancreas and the use of magnetic resonance cholangiopancreatography (MRCP), the proportion of patients with cholestasis included in the various studies decreased, and a different group of patients with intrapancreatic CBD strictures without cholestasis (morphological stricture) began to be included in the studies [13]. Overall, CBD strictures are today detected in about 30 % of patients affected by chronic pancreatitis who undergo ERCP for various reasons [14]. However, only approximately one-quarter of these patients show severe cholestasis significant enough to be considered for treatment [14].

Different population groups are another variable capable of explaining the divergences in the reported incidences of CBD strictures. Surgical series report a higher incidence in comparison with the total population of patients hospitalized for chronic pancreatitis (5.8 % to 45.6 % vs. 2.7 % to 9.9 %, respectively).

There was controversy in the past concerning the issue of whether asymptomatic patients with persistently elevated values in liver function tests should undergo treatment [4] [7] [15]. It is now well established, however, that in order to prevent the long-term complications resulting from persistent bile duct obstruction, these patients definitely require biliary drainage [16] [17].

The historical gold standard treatment for these strictures is surgical bilio-enteric by-pass. However, although there are no prospective controlled data comparing surgery with endoscopic treatment, there has been an increasing number of studies reporting the long-term benefit of endoscopic biliary drainage in this setting [14] [18] [19] [20] [21] [22] [23] [24].

One of the arguments against immediate surgery is the potential spontaneous regression and disappearance of cholestasis, reported in 3 - 27 % of patients [3] [25]. Unfortunately, in these studies, the exact incidence of strictures is unknown and the most probable causes of cholestasis other than stenosis were alcoholic hepatitis, hepatic steatosis, biliary stones, and others. The frequency of complete disappearance of cholestasis after its onset in patients with intrapancreatic strictures is also unknown, as there have been no recent prospective studies on the natural history of cholestasis in this subpopulation. In 1990, Frey et al. [17] found that the increase in alkaline phosphatase and bilirubin levels may be transient in half or more of patients with chronic pancreatitis complicated by CBD stenosis. In these patients, the most probable event is the development of intrapancreatic strictures due to edema secondary to an acute phase of chronic pancreatitis; once the acute phase has passed, reduced edema leads to complete resolution of the cholestasis.

Unfortunately, no predictive factors are available that would be capable of identifying patients in whom cholestasis will eventually disappear. To avoid unnecessary surgery, systematic endoscopic placement of a plastic stent therefore appears to be more than reasonable when a symptomatic biliary stricture secondary to chronic pancreatitis is diagnosed. The stent should then be removed after 1 - 3 months, and the stricture should be reevaluated. The most important question is then what ought to be done if the stricture has persisted. Is it wise to continue with endoscopic drainage?

Prolonged biliary plastic stenting for strictures caused by chronic pancreatitis is a well-established procedure, with a long-term success rate of 10 - 80 % (mean 32 %) in follow-up periods ranging from 14 to 52 months [14] [18] [19] [20] [21] [22] [23] [24]. The inconveniences associated with the presence of a plastic stent in the common bile duct are acceptable in patients receiving palliative treatment for malignant biliary strictures, because of their short life expectancy. In patients with chronic pancreatitis, even if surgery can be avoided in one-third of the cases, the risk of severe and potentially fatal complications such as suppurative cholangitis due to plastic stent clogging or dysfunction [14] has to be critically considered. In patients who are unfit for surgery, alternative nonsurgical options therefore need to be appraised.

Kahl et al. [24] analyzed predictive risk factors for failure of endoscopic plastic biliary stents used to treat strictures secondary to chronic pancreatitis. Sixty-one patients with symptomatic CBD strictures were evaluated. The stents were left in place for 1 year, with scheduled stent exchanges every 3 months. After the treatment period, all of the patients entered a follow-up program. During a median follow-up period of 40 months (range 18 - 66 months), the stricture disappeared in 16 patients (26.2 %). Among the tested variables, calcifying pancreatitis was the only negative predictive factor: of 39 patients affected by chronic calcifying pancreatitis, only three (7.7 %) were successfully treated, whereas the treatment was successful in 13 of 22 patients (59.1 %) without calcifications (P < 0.001). In a more recently published paper, Draganov et al. [26], recorded similar results using multiple plastic stenting in a small group of patients. There were three successes in three patients with noncalcifying pancreatitis (100 %), compared with one of six patients with the calcifying form (17 %). This observation may in part explain the unusually high success rate recorded by Vitale et al. [22], who reported an 80 % rate of resolution of biliary strictures after plastic stenting. Only four of 20 patients had the calcifying form in their group studied. Pancreatic fibrosis is closely related to the presence of pancreatic calcifications, and its presence significantly reduces the chances of stricture resolution. As a consequence, plastic biliary stenting should be considered as a temporary treatment, especially in patients affected by a calcified form of chronic pancreatitis. The use of plastic stents for long periods (more than 1 year) in nonresponding patients should be reserved only for high-risk patients or for those who refuse surgery.

Ten years ago, Devière et al. [27] proposed an alternative endoscopic approach. They reported on the long-term outcome with self-expandable metal stents (Wallstent, Boston Scientific, Natick, Massachusetts USA) in 20 patients who were not necessarily unfit for surgery. Eleven of the 20 patients had previously received treatment with 10-Fr plastic stents for approximately 15 months. An uncovered Wallstent 34 mm long - long enough to pass the stricture, but short enough not to compromise a further hepaticojejunostomy - was used in all cases. Patients were followed with ultrasound and laboratory studies every 3 months and underwent ERCP every 6 months for 2 years. During the follow-up period (mean 33 months, range 24 - 42 months), it was observed - using ERCP in 20 cases and cholangioscopy in five - that the Wallstents were fully covered with mucosa. Two patients had early stent occlusion due to intraluminal mucosal hyperplasia at 3 and 6 months, respectively. Luminal patency was maintained in the remaining 18 patients during the follow-up period.

In this issue of Endoscopy, an original paper by the Amsterdam group [28] presents the results of metallic biliary stenting in biliary strictures secondary to chronic pancreatitis in a subset of 13 patients in whom surgery was contraindicated or refused for fear of the operation. A plastic stent had previously been inserted for a mean of 6 months in all cases, in order to exclude patients in whom the stricture might eventually have resolved. The indications for metal stent placement were: relative contraindication to surgery in 10 patients, suspected unresectable pancreatic carcinoma in one, another type of malignancy in another case, and refusal of surgery in the last. At the end of the follow-up period (mean 60 months), nine patients (69 %) had good bile duct drainage. This group included five patients with a well-functioning first stent, three with a second stent inserted inside the first occluded Wallstent, and one patient who required three ERCPs to extract biliary sludge from the CBD during the follow-up period. The treatment was described as unsuccessful in the last four patients. Stent occlusion occurred in three of these cases; the endoscopist, who decided to follow his own experience and not a prospective protocol, reinserted a plastic stent inside the metallic one. In the fourth case, the stent migrated distally. Interestingly, the actuarial patency curve at a follow-up of 80 months was about 70 %. In this highly selected group, placement of a metal stent may be a wise alternative to surgery, in view of the long life expectancy, the high percentage of stent patency at a mean of 6.5 years, and since later surgical treatment is not compromised.

Only uncovered Wallstents were used in this study and the earlier one by Devière et al. [27]. The results obtained by Devière et al. might perhaps be improved today with the newer covered metal stents. In our experience, observation of some of these stents after removal more than 1 year after placement in patients with malignancies showed that the covered part was still intact, despite the long period inside the bile duct. Are these stents really better than the uncovered ones? Only a prospective comparative study will be capable of answering this question.

Self-expandable nitinol stents, which have a lower radial force than the Wallstent, could be of interest in this setting. These stents are able to preserve the shape of the ducts and, when the bile duct has a bent shape, they avoid medial impaction of the proximal end of the stent into the bile duct wall. Does this type of stent perform better than the Wallstent? Again, prospective studies are needed.

From onset to burn-out, the natural history of chronic pancreatitis is characterized by the development of multiple complications, such as pancreatic, biliary, and duodenal strictures, pseudocysts, and portal and/or splenic thrombosis. Surgery at the time of onset does not prevent the progression of the disease, as was shown by Amman et al. [29]. In a large group of patients undergoing surgery for chronic pancreatitis who were followed up prospectively, the need for a second surgical intervention was required in one-third of cases. Endoscopic treatment of chronic pancreatitis, despite the need for repeated treatments in some cases, could therefore be a suitable therapeutic option in order to delay surgery. In other words, therapeutic endoscopy may sometimes be able to provide a temporary bridge, deferring (or avoiding) the surgical option in order to prevent the need for repeated surgery. Before the advent of metal stents, plastic biliary stenting was the weak point in the endoscopic armamentarium for chronic pancreatitis. The actuarial patency of roughly 70 % after an 80-month follow-up period with the uncovered Wallstent suggests that this is a convincing therapeutic alternative, both in patients who are unfit for surgery and in those who may possibly need bridging therapy before surgery.

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