Expandable biliary stents: more questions than answers

THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2000 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.

Vol. 95, No. 3, 2000 ISSN 0002-9270/00/$20.00 PII S0002-9270(00)00702-4

EDITORIALS Expandable Biliary Stents: More Questions Than Answers Pancreatic cancer affects 8 –10 patients per 100,000 population (1) and typically presents in elderly patients with obstructive jaundice. The only curative approach is surgical excision. However, this is possible in only a minority of patients; therefore, survival beyond 5 yr is exceptional (2). With improved diagnostic and staging modalities (such as endoscopic ultrasound), most patients are managed palliatively. Because the most common presenting symptom is jaundice, biliary drainage is a critical step in the palliation of these patients, who usually have distal common bile duct strictures. As surgical bypass is associated with increased morbidity and mortality as well as longer hospital length of stay, endoscopic placement of biliary endoprosthesis has become a widely accepted procedure for palliation of obstructive jaundice (3, 4). The technique for inserting a 10F biliary stent for malignant distal CBD obstruction was described as early as 1980 by Soehendra and Reynders-Frederix (5). Since that time, equipment has become standardized and techniques modified until success rates for endoscopic relief of jaundice approach 90%. Typically, a 10F or 11.5F straight or curved polyethylene stent with side flaps is inserted so that it traverses the stricture, thereby restoring biliary flow. The major limitation of plastic stents stems from the formation of a “biofilm” along the inner surface, which ultimately leads to accumulation of biliary debris and stent occlusion (6). Occlusion rates for plastic stents vary considerably, but mean patency is approximately 3– 6 months. Because many plastic stents will have to be replaced, methods of prolonging stent patency have been investigated. Attempts using aspirin, antibiotics (7), gallstone dissolutional agents, mucolytics, and choleretic agents have all been disappointing (6, 8). Stent surface modification with silver coating or new polymers producing an ultrasmooth surface have also met with minimal success (9 –11). The development of expandable metal stents in 1989 introduced another method of prolonging biliary flow. The first question regarding expandable biliary stents is, “Do metal stents remain patent longer than their plastic counterparts?” At least five randomized, controlled trials have compared expandable biliary metal stents to plastic endoprosthesis (12–16). Although there appears to be no difference in mortality between metal and plastic, in all five studies metal stents demonstrated superior patency rates. Interestingly, these studies used Wallstents (Schneider, Minneapolis, MN). The largest of these trials was the US Wallstent Study Group trial, in which 182 patients with malignant, inoperable, distal biliary obstruction were randomized. In this study, at 30 days, 25% of plastic stents were

occluded (sludge occlusion) and only 5% of Wallstents were occluded (tumor ingrowth). The mean time to stent occlusion was prolonged in the metal stent group to 132 days, approximately twice that of the plastic stents (12). Of some concern is the fact that a European trial of metal stents (of similar design), found that the median time to occlusion of the metal stents was more than twice as long (273 days) as the US Wallstent study (13). Furthermore, the median time to occlusion of the plastic stent group in Europe (126 days) was greater than the metal stent group in the United States (111 days). The reasons for these differences are unclear. Despite these statistical limitations, it seems justified to conclude that, overall, metal stents employed for distal malignant biliary obstruction remain patent longer than plastic stents. The next question is, “Are expandable biliary stents cost effective?” Cost analysis has concentrated on patency rates, repeat ERCPs, and total hospital length of stays. Of critical importance in determining cost-efficiency is the length of survival of each patient. Because plastic stents can play a palliative role (sometimes for extended periods of time), only patients that “outlive” their stent will benefit from a stent that remains patent longer (i.e., metal). In the European Wallstent study by Davids et al., the median survival was 147 days for the patients in the polyethylene stent group with a median stent patency of 126 days (13). In the David study, only 30 of 56 patients (who occluded their plastic stents) had an opportunity to benefit from a metal stent that provided patency for a longer period. Only these patients could have benefitted from a metal stent, as only these patients occluded their plastic stent. The other 26 never occluded their plastic stent and, therefore, would not have benefitted from a metal stent. Because occlusion rates are dependent on survival, the longer a patient survives, the more likely a metal stent will be beneficial (as plastic stents occlude earlier than metal). Despite the initial heavy cost of expandable metal stents (30 – 40 times that of the plastic stents), in patients surviving ⬎4 – 6 months, the metal stents ultimately (because of longer patency periods) prove to be the least expensive method of relieving biliary obstruction (13). As discussed by Prat et al., the overall cost of a metal stent is greater than that of a plastic stent if the patient survives ⬍3 months (15, 17). For patients who survive ⬎3– 6 months, the cost-benefit shifts in favor of a metal stent, especially if it is inserted early in the course of therapy (18). It seems reasonable to state, therefore, that metal stents are likely cost-effective for treating patients with malignant distal biliary obstruction who are likely to survive 4 – 6 months. If the critical issue in cost-effectiveness is survival duration, criteria for estimating survival are required. Patients with small tumors (⬍3 cm) and normal albumen are more likely to survive ⬎6 months than those without these crite-

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ria, thereby making them the best candidates for these stents. Those patients with large tumors, evidence of metastasis, poor performance scores, and anaplastic histology represent a group for which it would not seem cost-beneficial to insert a metal stent (17). Unfortunately, even with criteria that demonstrate cost-effectiveness, decreasing reimbursement rates and escalating overall hospital expenditures may limit some centers’ use of these metal stents. In fact, in some Canadian centers, funding for metal stents may indirectly come from the patient or from other research funds not raised by the hospital. Having determined that the literature supports use of expandable metal stents in appropriate patients, the next question is “Which expandable metal stent is the best?” Currently, four expandable metal stents are regularly used in North America for biliary strictures. Wallstent (Schneider, Boston Scientific, Minneapolis, MN), Diamond Ultraflex (Boston Scientific, Natick, MA), Endocoil (Instent, Eden Prairie, MN) and Gianturco (Z-stent; Wilson Cook, Winston-Salem, NC), all of which have been studied in multiple trials. These stents are designed to be delivered endoscopically through a duodenoscope over a 0.035-guidewire, with the prepared system positioned across the malignant stricture with the aid of radiopaque markers on the delivery catheter. Technically, each of the four systems have some degree of stent shortening with delivery. This is most pronounced with the Endocoil, which can, at times, be technically difficult to insert. Several studies have demonstrated that, although the Endocoil has higher radial force (theoretically making it difficult for a tumor to constrict), technical employment difficulties and risk of tumor entrapment within the coils suggest a need for caution with this stent (despite its lower cost in some centers) (19 –21). In a study by Dumonceau et al., (22) in this issue of the journal, the use of Ultraflex Diamond stents and Wallstents for palliation of distal malignant biliary strictures is compared. The authors have previously published their extensive experience with expandable biliary stents (primarily Wallstents) (23–28). In the current study (22), they retrospectively compare results for 23 consecutive patients in whom they have inserted an Ultraflex Diamond stent with 23 matched patients who were treated with a Wallstent. Adequate biliary drainage was obtained in most patients (96% in each group), and early complications were uncommon. During follow-up, bile duct obstruction occurred in five of 22 of the Ultraflex Diamond patients and six of 21 of the Wallstent patients. Statistical analysis showed no difference in patency rates. The authors accurately point out that they would need to study 768 patients to show a statistical difference between the two stents. They conclude that, within the limitations of their study, the Ultraflex Diamond stent appears to be similar to the Wallstent. Their conclusions raise other questions. What are other experiences with the Ultraflex Diamond Stent? Recent experiences from others using the Ultraflex Diamond Stent have not been as successful as the study by Dumonceau et

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al (22). In three separate studies, reviewing over 50 patients with Ultraflex Diamond stents, patency rates appear to be statistically inferior to those of the Wallstent (29 –31). One possible explanation for decreased patency is the fact the diamond pattern provides a wider-spaced mesh for tumor ingrowth (the most common cause of obstruction), and that the decreased radial force (advantageous for tortuous bile ducts) of this stent provides more opportunity for compression. Although these studies are retrospective, with inherent statistical flaws, three different authors recommend some degree of caution with the use of these metal stents (29 –31). The next question to consider is, “How are most gastroenterologists deciding which metal stent to insert?” There are precious few data to guide the choice of metal stents by community gastroenterologists. Likely, most of them follow the advice or example of the larger referral center in their area. Unfortunately, the choice of a metal stent by the tertiary-care center may reflect ongoing studies or preferential cost reductions by manufacturers to encourage the use of their stent by “high-profile” centers. As long as metal stents are selected based on cost, the stent with the longest patency may not be used. Adequate trials comparing different metal stents [as noted in the study by Dumonceau et al. (22)] are going to be extremely difficult to perform and, unfortunately, retrospective and prospective cohort analysis will likely be relied upon for guiding stent selection. So what have we learned about metal stents? We have learned that, overall, they appear to have longer patency rates than their plastic counterparts. We have also learned that several variables (albumen, tumor size, histology, weight loss) may be critical in deciding whether the patient will survive ⬎6 months and, therefore, whether insertion of a metal stent would be cost-effective. Most experience has been gained with the Wallstent; despite the study in this issue (22) supporting the use of the Ultraflex Diamond stent, caution must be advocated when trying to compare metal stents, as only very large randomized trials can ever show statistical differences. Perhaps the real future of metal stents will depend on design improvements, such as the addition of a “cover” to inhibit tumor ingrowth or impregnation of the stent with chemotherapeutic or radioactive agents. Preliminary data seem encouraging but, again, large randomized trials are required before we can make true comparisons (32–34). For expandable biliary stents, unfortunately, there are still more questions than answers. Robert A. Enns, M.D., F.R.C.P. St. Paul’s Hospital University of British Columbia Vancouver, British Columbia, Canada

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Reprint requests and correspondence: Robert A. Enns, M.D., F.R.C.P., St. Paul’s Hospital, University of British Columbia, #300 –1144 Burrard Street, Vancouver, BC, Canada V6Z 2A5. Received Nov. 10, 1999; accepted Dec. 8, 1999.

Analyzing Hospital Costs for Patients With Inflammatory Bowel Disease In this issue, Bernstein et al. (1) describe an analysis of the direct hospital costs of surgical and medical therapies in inflammatory bowel disease. In this era of limited health care resources, cost analysis is crucial— especially in diseases such as inflammatory bowel disease, which have several therapeutic options. This analysis was prompted by a report that the majority of the costs of Crohn’s disease result from surgical intervention (2). Bernstein et al. appropriately used direct costs to improve the generalizability of their results to other centers. They classified patients based on surgical versus medical management and “digestive” versus