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Digestive and Liver Disease 42 (2010) 765–766

Contents lists available at ScienceDirect

Digestive and Liver Disease

journa l homepage: www.e lsev ier .com/ locate /d ld

ommentary

he long term use of covered metal stents in managing malignant biliary

bstruction. Are we changing outcomes?

ergio Crespo, Massimo Raimondo ∗

ivision of Gastroenterology & Hepatology, Mayo Clinic Florida, United States

. Plastic versus metal

Endoscopic placement of indwelling biliary stents has becomehe standard of care for palliation of jaundice in patients with unre-ectable obstructing malignant tumours. The use of plastic stentsPS) has been hampered by early occlusion requiring replacementvery 3 months, stent migration and placement difficulty for stentsarger than 10 F through standard side-viewing therapeutic duo-enoscopes. As a result of the deficiencies of PS, a self-expandingetal stent (SEMS) was developed in the hope of prolonging stent

atency and reducing the need for repeat intervention. Since theallstent (Boston Scientific, Watertown, MA) was introduced in

990, SEMS placement has become the treatment of choice fornresectable, malignant, biliary obstruction in patients expected tourvive longer than 3 months. Initial randomised studies compar-ng SEMS with PS demonstrated longer patency rates and decreasedates of cholangitis [1–3]. However, obtaining proper positionings challenging due to expected foreshortening of the stent. Migra-ion is occasionally an issue, as is tissue ingrowth through the open

esh of the SEMS, tumour overgrowth of the end of the prosthe-is and deposition of debris. A number of studies have observed9–40% Wallstents’ occlusion rates [2,3]. As a result, new SEMSenerations have been developed with variations in diameters (6-o 10-mm varieties), the use of nitinol, conformation and size ofhe wire opening, delivery system improvements with eliminationf foreshortening, mechanisms of expansion and the addition of alastic coating of the wire mesh.

. Covered versus uncovered

The value of covered SEMS versus uncovered SEMS remains

nclear. Loew et al. compared the 10-mm Wallstent and the 6-nd 10-mm Zilver stents (Cook Medical, Winston-Salem, NC) onn intent-to-treat basis [5]. Analysis revealed a statistically signif-cant and higher-than-expected occlusion rate of the 6 mm Zilver

DOI of original article:10.1016/j.dld.2010.02.011.∗ Corresponding author at: Division of Gastroenterology & Hepatology, Mayolinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224, United States.el.: +1 9049537382; fax: +1 9049537260.

E-mail address: raimondo.massimo@mayo.edu (M. Raimondo).

590-8658/$36.00 © 2010 Published by Elsevier Ltd on behalf of Editrice Gastroenterologoi:10.1016/j.dld.2010.08.008

stents when compared with occlusion rates of both 10-mm Wall-stent and Zilver stents (39% versus 21–23%, respectively). There wasno difference occlusion rate between the two 10-mm stents. Fur-thermore, Soderlund and Linder showed patency and survival ratesof covered SEMS were lower than the rates reported for uncoveredSEMS [4]. However, these results may be explained by other causesof obstruction associated with covered SEMS, such as occlusioncaused by debris and migration.

Partially covered metal stents (PCMS) were developed to resisttissue ingrowth. Furthermore, the demonstration of PCMS remov-ability has prompted expanded indications for their use to includeplacement for distal pancreatico-biliary malignancy regardlessof resectability. Nonetheless, several complications have beenreported, including migration in benign strictures and cholecys-titis. One study in 396 patients observed complications in 18% ofpatients with a mean time of occurrence 159 days after stent place-ment. There were six cases of stent occlusion due to debris orsludge (1.6%), four cases of tumour overgrowth (1%) and three casesof benign stenosis in the uncovered portion of the PCMS (0.8%).Tumour overgrowth was managed by replacement with PS in twocases and replacement with PCMS in the other one [6]. However,little long term data regarding the long term survival in patientsundergoing PCMS placement exists.

3. Outcome measures

Due to the relative novelty of covered SEMS, there is very lit-tle published data regarding the long term outcomes of coveredSEMS. Ornellas et al. [7] retrospectively assessed the effectivenessand safety of covered SEMS placement either as primary treatmentor reintervention in patients requiring palliation of malignant bil-iary obstruction. One-hundred and four patients received coveredWallstent biliary endoprosthesis (Boston Scientific, Natick, MA).Forty-eight patients received covered SEMS as a primary interven-tion. In 56 patients the procedure was a reintervention to replace orrecanalise a previous stent. At 12 months, covered SEMS remainedpatent in 48% of the reintervention group compared with 82% of

the patients who underwent stent placement as a primary inter-vention. Although this was not statistically significant, there wasa strong trend towards longer primary SEMS patency. Survival inthe reintervention group was significantly longer versus the pri-mary intervention group (median survival 107 days for primary

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66 S. Crespo, M. Raimondo / Digestiv

ntervention versus 178 days for secondary intervention). However,here were nearly twice as many patients with metastatic diseaset primary intervention compared to patients who underwent rein-ervention. Survival was not affected by the presence of metastaticisease, distal or mid common bile duct stricture location, age >80ears, male sex, or chemoradiation before or after SEMS placement.

Cho et al. [8] retrospectively evaluated patients who underwentecondary biliary stent insertion for prior biliary stent occlusion.hey categorised three groups of patients based on whether theyeceived covered SEMS, bare-SEMS alone, or a plastic stent. Theedian stent patency duration for initial covered and bare-SEMSere statistically similar. As for revision stent placement, they

ound a median stent patency of 138, 109, and 88 days for covered,ncovered, and plastic stents, respectively. The use of covered SEMSt revision showed a significantly longer patency than PS, but notompared to bare metal stents. Multivariate analysis showed theombination of bare-SEMS had a worse cumulative stent patencynd survival time compared to the use of covered SEMS. Patientsith ampulla of Vater cancer had better stent patency and survival

han those with other pancreatobiliary malignancies. Antitumourreatment also prolonged survival time. Controlling for patient age,ausative disease and antitumour treatment, bare-SEMS had 2.0imes the risk of occlusion SEMS and 2.4 times the risk of deathuring follow-up compared to covered SEMS. They suggested thatEMS placement using at least one covered SEMS (in the primarynd/or secondary procedure) might provide longer cumulativetent patency and survival than using uncovered SEMS in bothrocedures.

. The search for predictors of mortality

In this issue of Digestive and Liver Disease, Mahajan et al.erformed a single centre prospective trial aimed to define the

ndependent predictors of mortality in patients undergoing PCMSevision [9]. Two-hundred and forty-eight patients with malignantistal biliary obstruction underwent PCMS (Wallstents partiallyovered with Permalume®, Boston Scientific, Natick, MA) place-ent over 5 years. The patients had routine follow-up every 3onths until death or stent dysfunction. Forty-two patients (17%)

equired removal of the PCMS, mostly due to migration (43%).cclusion or tumour overgrowth occurred in 9.5% of patients.he causes of malignant obstruction were pancreatic cancer,holangiocarcinoma, carcinoid tumour, ampullary carcinoma andymphoma. Other reasons for removal included malposition, needor tissue biopsy, cholecystitis, persistent cholestasis, cholangitisnd liver abscess. Thirty-one patients with unresectable diseasenderwent stent replacement with a new PCMS with a medianollow of 35 weeks. Post stent replacement, they found a sur-ival rate of 29% at 10 months in patients with unresectableisease (n = 31). Multivariate analysis for age, gender, and expo-ure to adjuvant chemotherapy and/or radiotherapy in this groupf patients showed that adenocarcinoma was an independent riskactor for death. Given the cost, risks of the procedure and short lifexpectancy of patients with biliary obstruction due to adenocarci-oma, the authors suggested placing a PCMS at revision might not

e justifiable. However, they recommended PCMS revision shoulde undertaken when dealing with a non-adenocarcinoma type can-er.

The strength of the authors’ findings includes the prospectiveesign and long follow-up period. Furthermore, this study sheds

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Liver Disease 42 (2010) 765–766

light on predictors of long term mortality in patients with unre-sectable disease. In particular, their findings confirm that aetiologyof bile duct obstruction, in particular strictures caused by adeno-carcinomas, may affect long term survival outcomes. Interestingly,the authors noted treatment with adjuvant chemotherapy and/orradiotherapy did not affect long term survival. This may be a reflec-tion of the long follow-up period and inherit mortality of metastaticdisease progression. The main limitation of the study is the smallnumber of patients analysed. Larger sample size may allow dissec-tion of the intricate details that may affect stent patency and longterm survival such as tumour size, location, presence or absenceof metastasis at initial and subsequent stent placement and ongo-ing chemo-radiotherapy. In addition, no group was included in theanalysis to assess the relative benefit, or lack of, in placing a PCMSversus a bare-SEMS.

The authors appropriately raise the questions whether contin-ued SEMS placement should be undertaken in all patients withmalignant biliary obstruction. Overall, the most important goalfor palliative SEMS placement is to maintain patency until thepatient’s death. This in turn minimises need for further inter-vention and improves quality of life. However, consideration tothe risk of complications must be weighed, particularly address-ing the rate of stent migration, tumour progression and occlusionrates with PCMS. Another important factor in stent selection inthis patient subset is cost, an issue that definitely cannot beignored.

In summary, Mahajan et al. have shed light on the subtledifferences in patients with malignant biliary obstruction thatmay affect long term stent patency and importantly survival.Further prospective trials are indeed necessary to hopefully defini-tively provide guidance in the management of malignant biliaryobstruction.

Conflict of interest statementNone declared.

References

1] Andersen JR, Sorensen SM, Kruse A, et al. Randomised trial of endoscopicendoprosthesis versus operative bypass in malignant obstructive jaundice. Gut1989;30:1132–5.

2] Davids PH, Groen AK, Rauws EA, et al. Randomised trial of self-expanding metalstents versus polyethylene stents for distal malignant biliary obstruction. Lancet1992;340:1488–92.

3] Kaassis M, Boyer J, Dumas R, et al. Plastic or metal stents for malignant stricture ofthe common bile duct? Results of a randomized prospective study. GastrointestEndosc 2003;57:178–82.

4] Soderlund C, Linder S. Covered metal versus plastic stents for malignant com-mon bile duct stenosis: a prospective, randomized, controlled trial. GastrointestEndosc 2006;63:986–95.

5] Loew BJ, Howell DA, Sanders MK, et al. Comparative performance of uncoated,self-expanding metal biliary stents of different designs in 2 diameters: finalresults of an international multicenter, randomized, controlled trial. GastrointestEndosc 2009;70:445–53.

6] Ho H, Mahajan A, Gosain S, et al. Management of complications associated withpartially covered biliary metal stents. Dig Dis Sci 2010;55:516–22.

7] Ornellas LC, Stefanidis G, Chuttani R, et al. Covered Wallstents for palliation ofmalignant biliary obstruction: primary stent placement versus reintervention.Gastrointest Endosc 2009;70:676–83.

8] Cho JH, Jeon TH, Park JY, et al. Comparison of outcomes among secondary cov-

ered metallic, uncovered metallic, and plastic biliary stents in treating occludedprimary metallic stents in malignant distal biliary obstruction. Surg Endosc 2010[Epub ahead of print] PMID: 20602138.

9] Mahajan A, Ho H, Jain A, et al. Mortality in patients undergoing covered self-expandable metal stent revisions in malignant biliary stricture: does pathologymatter? Dig Liver Dis 2010, doi:10.1016/j.dld.2010.02.011.