Biliary Stenting for Unresectable Malignant Biliary Obstruction

Biliary self-expandable metallic stent for unresectablemalignant distal biliary obstruction: Which is better:covered or uncovered?

Hiroyuki Isayama, Yousuke Nakai, Hirofumi Kogure, Natsuyo Yamamoto andKazuhiko Koike

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Self-expandable metallic stents (SEMS) are a widely acceptedbiliary endoprosthesis for patients with unresectable malignantdistal biliary obstruction. There are two types of SEMS: coveredand uncovered. Uncovered SEMS (UCSEMS) embed into thebiliary wall due to their mesh structure and self-expandability,and are resistant to migration. However, the disadvantage ofUCSEMS is occlusion due to tumor ingrowth (TI) via the stentmesh, and TI is the main cause of UCSEMS occlusion. To over-come this, covered SEMS (CSEMS) were developed and showedlonger patency than UCSEMS. However, migration due to thenon-embedded stent body is the main cause of CSEMS dysfunc-tion. There are some randomized studies comparing CSEMS andUCSEMS; however, the results are different according to eachstudy. From one meta-analysis, CSEMS showed longer patencythan UCSEMS. A literature review revealed that covered SEMS

showed longer patency than UCSEMS. Some studies cannotclearly demonstrate the superiority of CSEMS, as the CSEMS useddid not prevent TI or migration. Mechanical properties of SEMSmay influence the occurrence of complications. A recent clinicalstudy comparing the Covered Wallstent and the Covered WallFlexrevealed superiority of the WallFlex for the prevention of migra-tion. Reducing the axial force and increasing the radial force maylead to good results. Migration of CSEMS should be prevented bytaking into consideration the mechanical properties of stents anddevelopment of anti-migration systems.

Key words: biliary obstruction, biliary stent, covered metallicstent, endoscopic procedure, self-expandable metallic stent(SEMS)

INTRODUCTION

ENDOSCOPIC BILIARY STENTING for unresectabledistal malignant biliary obstructions (MBO) is a widely

accepted palliative procedure.1–4 The length of patency andthe incidence of complications influence the quality of life ofpatients. Endoprostheses have been improved to prolongstent patency and reduce the incidence of complications.There are three types of stents used for the management ofan unresectable distal MBO: plastic, uncovered metal, andcovered metal stents. In this review, the characteristics,advantages/disadvantages, and clinical outcomes of thosestents are discussed. The aim of the present study was tocompare covered and uncovered metal stents.

UNCOVERED SELF-EXPANDABLEMETALLIC STENTS

SELF-EXPANDABLE METALLIC STENTS (SEMS)were developed to overcome the disadvantages of the

plastic stent (PS). Patency of the PS differs according to boresize, but is limited by the accessory channel of the endo-scope to 12 Fr. A PS with a larger bore size shows longerpatency because the main cause of occlusion is accumulationof biliary sludge.5 PS of 14 Fr can be used with TJF-M20(Olympus Co., Tokyo, Japan). However, the disadvantages of14-Fr PS are the difficulty of insertion and they sometimesbecome dislocated. The diameter of a SEMS is approxi-mately 30 Fr (10 mm) after deployment and in somerandomized studies, uncovered SEMS (UCSEMS) showsignificantly longer patency than PS.6–9 The other advantageof UCSEMS is its ability to embed into the biliary wall,10

which may prevent stent migration and reduce sludge accu-mulation because little metal wire is exposed in the bile duct.However, UCSEMS cannot be removed after placementunless there is an obstruction, and an additional stent

Corresponding: Hiroyuki Isayama, Department of Gastroenterol-ogy, Graduate School of Medicine, The University of Tokyo, 7-3-1,Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Email: isayama-2im@h.u-tokyo.ac.jpReceived 30 November 2012; accepted 1 February 2013.

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insertion is required. In summary, the advantages ofUCSEMS are based on their self-expandability and wire-mesh structure.

COVERED SEMS

THE DISADVANTAGE OF UCSEMS is derived fromits wire-mesh structure. This type of structure cannot

prevent tumor ingrowth (TI) via the stent mesh, and the maincause of occlusion of UCSEMS is TI. In previous reports, theincidence of occlusion as a result of TI is 20–50%.6–9

Covered SEMS (CSEMS) were developed with a thin andflexible membrane to prevent TI.11,12 CSEMS do not embedinto the biliary wall, and can be removed after placement,unlike UCSEMS. Placement of CSEMS is not as stressfulbecause of their removability, and UCSEMS perform as wellas large-size PS. The patency of CSEMS is longer than thatof UCSEMS.13–18

The disadvantage of CSEMS is also based on the coveringmembrane. Removing the membrane may lead to migration,and a non-embedded membrane can result in sludgeaccumulation.

COMPARISON OF CSEMS AND UCSEMS

SEVERAL RANDOMIZED CONTROLLED studies(RCT) and one meta-analysis have been published.19–25 A

review of the RCT is shown in Table 1. We previously pub-lished the first RCT in this field using original polyurethane-covered diamond stents (Microvasive; Boston ScientificCorp., Natick, MA, USA).19 In that study, we showed thesuperiority of CSEMS stent patency and cost-effectivenesscompared to UCSEMS. No TI was observed, and only 2%migration occurred in the CSEMS cases. The problem wasthat we used a hand-made CSEMS; thus generalizing theresults to manufactured products is difficult. Krokidis et al.published two RCT on limited causative disease in pancre-atic cancer and cholangiocarcinoma.20,21 They used Viabilbiliary stents (W. L. Gore & Associates, Flagstaff, AZ,USA), and no TI or migration was observed. However, thisCSEMS is not commercially available in Japan. Kitano et al.presented a RCT to the American DDW 2012.22 They usedcurrent commercially available covered and uncovered Wall-Flex (Microvasive; Boston Scientific Corp.) stents andshowed the superiority of CSEMS in terms of patency. No TIor migration was observed. Thus, CSEMS that do notmigrate or cause TI show good results.

Two RCT were published at the same time in the samejournal in 2010.23,24 Telford et al. compared partially coveredWallstents from the USA (Microvasive; Boston ScientificCorp.) (n = 68) with uncovered Wallstents (n = 61).23 Nosignificant difference in patency was observed as a result ofthe relatively high incidence of TI (9%) and migration (9%)

Table 1 Review of RCT: Covered vs uncovered stents

Study Group No.pts

Stenttype

Coveringmaterial

Pancreaticcancer (%)

Occlusion(%)

Cause of occlusion Migration(%)

Patency(mediandays)

Which isbetter?

TI (%) TO (%) Sludge (%)

Isayamaet al.19

C 57 Diamond Partiallypolyurethane

59 14 0 50 25 2 225† C

U 55 Diamond – 38 76 9 0 0 193†

Krokidiset al.20

C 30 Viabil FullePTFE/FEP

0 13 0 50 50 0 227† C

U 30 Wallstent – 30 89 11‡ 11 0 166†

Krokidiset al.21

C 40 Viabil FullePTFE/FEP

100 10 0 50 0 0 234† C

U 40 Luminexx – 30 92 10‡ 8 0 166†

Kitanoet al.22

C 60 Wallflex Partiallysilicone

100 23 0 21 8 0 285 C

U 60 Wallflex – 37 71 9 27 0 222Kullman

et al.24

C 200 Nitinella Partiallypolyurethane

77 24 19 30 6 3 154 ND

U 200 Nitinella – 23 45 22 2 0 199Telford

et al.23

C 68 Wallstent Partiallysilicone

86 53 17 9 11 12 357 ND

U 61 Wallstent – 77 45 30 0 4 0 711

†Data shown are means.‡Tumor ingrowth and overgrowth.C, covered; ND, no difference; pts, patients; RCT, randomized controlled trials; TI, tumor ingrowth; TO, tumor overgrowth; U, uncovered.

72 H. Isayama et al. Digestive Endoscopy 2013; 25 (Suppl. 2): 71–74

© 2013 The AuthorsDigestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society

in the CSEMS group. Kullman et al. reported a very largeSwedish study (n = 400) that compared the polycarbonate-polyurethane covered nitinol stent (Nitinella; ELLA-CS,Hradec Kralove, Czech Republic) with an uncovered stent.24

This large study also could not clearly demonstrate the supe-riority of CSEMS. In that study, the incidence of tumorin-/overgrowth was 13% and that of migration was 3%.According to those two studies, CSEMS insertion may leadto poor results because of a failure to prevent TI and migra-tion. The authors of the present review article stated that theconcept of CSEMS is good, but the quality of current pro-duction is insufficient.26

A single meta-analysis, which included five RCT (RCT byKitano et al.22 was not included in this meta-analysis becauseit was published afterwards), has compared CSEMS withUCSEMS.25 CSEMS showed significantly longer durationsof both stent patency, defined by stent occlusion, and stentsurvival, defined by occlusion and migration, than didUCSEMS. The main cause of stent dysfunction was tumorovergrowth, sludge, and migration in the CSEMS group, andTI in the UCSEMS group. No significant difference in theincidence of cholecystitis or pancreatitis was identified.

MECHANICAL PROPERTIES OF SEMS

RADIAL AND AXIAL forces are associated withSEMS. Radial force (RF) is a well-known expansion

force that may be related to dilation of the stricture andmaintaining luminal patency,27 whereas the axial force (AF)is a new mechanical property proposed by us. AF is therecovery or straightening force when the SEMS is bent andis related to its conformability in the bile duct. SEMS arefixed by the tumor in the biliary tree, and both sides of theSEMS compress the biliary wall and cystic duct and pancre-atic orifices. This compression may cause inflammation ofthe bile epithelium, cholecystitis, and pancreatitis.28–30 Webelieve that a lower AF may be better for SEMS.

We recently published the results of the WATCH study,which compared partially covered Wallstent (PCW; oldmodel) and WallFlex (PCWF; current model) stents.31 ThePCW and PCWF are composed of wire material and have adifferent stent-end design. Use of nitinol for the stent wirematerial resulted in the AF of the PCWF being reduced by40% and the RF being increased by 30%. The end of thePCWF was flared and looped to prevent migration and tofacilitate removal. The median and cumulative times torecurrent biliary obstruction defined by stent occlusion,migration, and cholangitis without occlusion in the PCWFwere significantly longer than those of PCW (373 and 285days, respectively; P = 0.007). The stent occlusion rates weresimilar (21 and 26%) in both groups, but the incidence of

migration was different (8 and 17%; P = 0.019). Reducingthe incidence of migration may lead to better results. Reduc-ing AF, increasing RF, and providing an anti-migration flaremay be effective for preventing migration.

CONCLUSION

A LITERATURE REVIEW REVEALED that coveredSEMS showed longer patency than UCSEMS. Some

studies could not clearly demonstrate the superiority ofCSEMS, as the CSEMS used did not prevent TI or migra-tion. Migration of CSEMS should be prevented by takinginto consideration the mechanical properties of stents anddevelopment of anti-migration systems.

CONFLICT OF INTERESTS

AUTHORS DECLARE NO conflict of interests for thisarticle.

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