Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video)

ORIGINAL ARTICLE: Clinical Endoscopy

Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video) Anshu Mahajan, MD, Henry Ho, MD, Bryan Sauer, MD, MS, Melissa S. Phillips, MD, Vanessa M. Shami, MD, Kristi Ellen, RN, Michele Rehan, MS, Timothy M. Schmitt, MD, Michel Kahaleh, MD, FASGE Charlottesville, Virginia, USA

Background: Benign biliary strictures (BBS) have been endoscopically managed with placement of multiple plastic stents. Uncovered metal stents have been associated with mucosal hyperplasia and partially covered self-expandable metal stents with migration. Recently, fully covered self-expandable metal stents (CSEMSs) with anchoring fins have become available. Objective: Our purpose was to analyze the efficacy and complication rates of CSEMSs in the treatment of BBS. Design: CSEMSs (10-mm diameter) were placed in 44 patients with BBS. CSEMSs were left in place until adequate biliary drainage was achieved, confirmed by resolution of symptoms, normalization of liver function tests, and imaging. Setting: Tertiary care center with long-standing experience with metal stents. Patients: A total of 44 patients with BBS (28 men, median age 53.5 years) were included. The preprocedure diagnoses included chronic pancreatitis (n Z 19), gallstone-related strictures (n Z 14), post liver transplant (n Z 9), autoimmune pancreatitis (n Z 1), and primary sclerosing cholangitis (n Z 1). Intervention: ERCP with temporary CSEMS placement. Removal of CSEMSs was performed with a snare or rat tooth. Main Outcome Measurements: Stricture resolution and morbidity. Results: The median time of CSEMS placement was 3.3 months (interquartile range 3.0-4.8). Resolution of the BBS was confirmed in 34 of 41 patients (83%) after a median postremoval follow-up time of 3.8 months (interquartile range 1.2-7.7). Complications were observed in 6 (14%) patients after CSEMS placement and in 4 (9%) after CSEMS removal. Limitation: Pilot study from a single center. Conclusion: Temporary placement of CSEMSs for BBS may offer an alternative to plastic stenting. Further investigation is required to further assess safety and long-term efficacy. (Gastrointest Endosc 2009;70:303-9.)

Copyright ª 2009 by the American Society for Gastrointestinal Endoscopy 0016-5107/$36.00 doi:10.1016/j.gie.2008.11.029

Benign biliary strictures (BBS) occur as the result of a variety of etiologies, such as chronic pancreatitis (CP), anastomotic strictures from liver transplantation, inflammatory conditions (ie, primary sclerosing cholangitis), and choledocholithiasis, among others.1 These strictures can have a variety of presentations such as mild elevation in liver function tests, recurrent cholangitis, secondary biliary cirrhosis, and end-stage liver disease.2,3 Because of the serious and irreversible nature of some of these complications, prompt treatment of these strictures is essential.

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Abbreviations: BBS, benign biliary strictures CP, chronic pancreatitis; CSEMS, fully covered self-expandable metal stent; IQR, interquartile range. DISCLOSURE: The following author disclosed financial relationships relevant to this publication: M. Kahaleh has received grant support from Boston Scientific, Olympus, Alveolus, Conmed, and Cook Medical. All other authors disclosed no financial relationships relevant to this publication.

Fully covered SEMSs in benign biliary strictures

Mahajan et al

Capsule Summary

TABLE 1. Patient characteristics No. Age (y) Male (% men)

44 53.5 (47-61)

What is already known on this topic d

28 (64%)

Etiology CP

19 (43%)

Biliary stones

14 (32%)

In the treatment of refactory benign biliary strictures (BBS), uncovered metal stents lack long-term patency and have been associated with epithelial hyperplasia, and partially covered metal stents can be placed temporarily, but are associated with migration and epithelial hypertrophy.

What this study adds to our knowledge Liver transplantation

9 (20%)

Other

2 (5%)

Prior common bile duct stenting

14 (32%)

CP, Chronic pancreatitis. Values listed as number (%) or median (IQR).

d

In a pilot study of patients with BBS treated with fully covered self-expandable metal stents, stricture resolution was accomplished in 34 of 41 patients after a median post-removal follow-up time of 3.8 months.

the use of a fully covered metal stent with anchoring fins in patients with BBS.

PATIENTS AND METHODS Patients

Figure 1. Fluoroscopic image of a gallbladder stent placed before deployment of a CSEMS.

Surgery remains the definitive treatment for extrahepatic bile duct strictures with creation of an enterobiliary anastomosis.3-5 Percutaneous balloon dilation has been used but has been shown to be inferior to surgery5 and endoscopy.6-8 Compared with surgery, endoscopic stenting is less invasive and has lower complication rates with shorter hospital stays.8-11 Endoscopic stenting provides an attractive alternative in patients with BBS and does not compromise the option of surgery if it fails.12 Uncovered metal stents have been placed in refractory BBS.13-15 However, their long-term efficacy has been limited because of their lack of long-term patency.14,15 Their placement has been associated with epithelial hyperplasia, embedding the stent in the bile duct, making their removal extremely difficult.15 Partially covered metal stents can be removed and offer the option of temporary placement16-18 but are associated with migration19 and epithelial hypertrophy.20,21 These observations led us to study 304 GASTROINTESTINAL ENDOSCOPY Volume 70, No. 2 : 2009

Between November 2006 and February 2008, 44 patients (28 men, median age 53.5 years) with BBS were enrolled in a prospective study with fully covered selfexpandable metal stent (CSEMS) placement (Table 1). The inclusion criteria for enrollment were (1) age 18 years or older and (2) clinical symptoms of biliary obstruction. The exclusion criteria were (1) patients for whom endoscopic procedures were contraindicated, (2) patients with peripheral or hilar strictures, and (3) patients with suspected malignant strictures. Consecutive patients were enrolled if they fulfilled inclusion criteria in the absence of exclusion criteria. Patients were then followed up in clinic every 3 months until stricture resolution, stent removal, death, or as clinically indicated. All patients, with the exception of 3 who died of unrelated causes, underwent CSEMS removal. Clinical response to therapy and procedure-related morbidity were recorded. The study was approved by our institutional review board; all patients provided written consent for their procedures.

CSEMS insertion, deployment, and removal All procedures were performed with the patient under general anesthesia. CSEMSs placed were 10 mm in diameter and fully covered (Viabil, Conmed, Utica, NY). After biliary sphincterotomy, the length of each stricture was determined, and the origin of the cystic duct insertion was noted in patients with an intact gallbladder. The proximal CSEMS delivery system was advanced above the stricture over a guidewire, where the CSEMS (40, 60, 80, or 100 mm in length) was partially deployed and positioned within the stricture before complete deployment. When the gallbladder was present, CSEMSs were placed below www.giejournal.org

Mahajan et al

Fully covered SEMSs in benign biliary strictures

Figure 2. Fluoroscopic image of the deployed CSEMS beside the gallbladder stent with complete biliary decompression.

Figure 4. Fluoroscopic image of a CSEMS pulled through the working channel of the endoscope.

Figure 5. Fluoroscopic image after CSEMS removal. Figure 3. Fluoroscopic image of a CSEMS ensnared before removal.

the cystic duct. In cases where it was anticipated that the cystic duct would be covered by the CSEMS, a gallbladder stent was placed (6 patients) (Figs. 1 and 2). Removal was performed with the snare (Figs. 3-5, Video 1; available online at www.giejournal.org). In case of failure or when the stent was unraveling, a rat-tooth forceps was used after effecting a wire-guided balloon dilation within the stent to disimpact it from the bile duct. No overtube was used. The stent was removed through the working channel of www.giejournal.org

the endoscope unless its integrity was questioned. In a subset of patients, choledochoscopy by use of Spyglass (Boston Scientific, Natick, Mass) was performed after CSEMS removal. All procedures were performed by interventional endoscopists who perform at least 500 ERCPs a year.

Definition of events Patients were considered to have stricture resolution if symptoms resolved, cross-sectional imaging did not demonstrate biliary dilation, and no stricture was seen on the Volume 70, No. 2 : 2009 GASTROINTESTINAL ENDOSCOPY 305

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TABLE 2. Treatment characteristics CSEMS size (mm) 10  40

6 (14%)

10  60

19 (43%)

10  80

11 (25%)

10  100

8 (18%)

Stent time (mo)

3.3 (3.0-4.8)

Follow-up after removal (mo)

3.8 (1.2-7.7)

Gallbladder present

21 (48%)

CSEMSs below cystic duct

15

Gallbladder stent

6

CSEMSs removed*

41 (93%)

CSEMSs, Fully covered self-expandable metal stents. Values listed as number (%) or median (IQR). *CSEMSs not removed in 3 patients who died of unrelated causes.

TABLE 3. Outcomes and complications CP

All others

P value

Biliary stricture resolved*

34/41 (83%)

11/17 (65%)

23/24 (96%)

.01

Biliary stricture resolved (intention to treat)y

34/44 (77%)

11/19 (58%)

23/25 (92%)

.01

6 (14%)

2/19 (11%)

4/25 (16%)

.68

Pain

2

1

1

PEP

3

0

3

Bleeding

1

1

0

Procedure complications Placement complication

Removal complication

4 (9%)

1/19 (5%)

3/25 (12%)

Pain

1

1

0

PEP

3

0

3

4 (9%)

2/19 (11%)

Migration

2

1

1

Occlusion

1

1

0

Unravel during removal

1

0

1

3 (7%)

2/19 (11%)

Stent complications

Died Pneumonia

1

Liver cirrhosis

1

Metastatic colon cancer

1

2/25 (8%)

1/25 (4%)

.62

1.00

.57

CP, Chronic pancreatitis; PEP, post-ERCP pancreatitis. Values listed as number (%). P value based on the Fisher exact test. *Resolution based on individuals with stent removed. yIntention-to-treat analysis; includes 3 patients who died of unrelated causes.

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Fully covered SEMSs in benign biliary strictures

TABLE 4. Series reported covered metal stent placement for BBS

Study Cantu et al (2005)36

No. patients/ no. stents 14/14

Etiology CP

Stent type PCMS

Time to removal (median [range]) 21 mo (18-33)

Reason for removal (no. of stents) Hyperplasia (5)

Success 37.5% at 30 mo

Complications related to stent (no. of patients) Cholestasis (7)

Migration (2)

Cholangitis (5)

Not removed (7)

Duodenal migration (2) Cholecystitis (1)

Kuo et al (2006)32

3/4

OLT

Fully covered

32 d (0-49)

Misplacement (1)

100% at removal

Per operator (2) Kahaleh et al (2008)21

79/79

CP, OLT, BC, inflammatory, surgical

PCMS

4 mo (1-28)

Resolution of symptoms (65)

Septicemia (1) Misplacement (1)

90% at removal

Migration (11)

Stricture (6) Pain (2) Cahen et al (2008)34

6/6

CP

Fully covered

(3-6 mo)

Predefined interval

66% at removal

Migration (2) Recurrent stricture (1)

BBS, Benign biliary strictures; CP, chronic pancreatitis; PCMS, partially covered metal stent; OLT, orthotopic liver transplantation; BC, biliary calculi.

cholangiogram upon CSEMS removal. Final success was defined as clinical resolution of the stricture without the need for repeat stent placement. Complications that occurred that were unrelated to CSEMS insertion and removal were separated.

Statistics The primary end point analyzed was resolution of the biliary stricture after CSEMS removal. A multivariate logistic regression analysis of factors potentially predictive of success (eg, age, sex, previous stenting, CSEMS length, and etiology) was performed. The level of significance was set at P ! .05 in statistical analyses.

RESULTS Figure 6. Endoscopic images of CSEMSs deployed across the ampulla with anchoring fins pointed out.

The median time of CSEMS placement was 3.3 months (interquartile range [IQR] 3.0-4.8). Patients were followed up for a median of 3.8 months (IQR 1.2-7.7) after removal of the CSEMS. The CSEMS was removed in 41 (93%) patients (Table 2). The CSEMS was not removed in 3 patients who died of unrelated causes. Resolution of the BBS was confirmed in 34 of 41 (83%) patients who had the CSEMS removed. With intent-to-treat analysis, 77% (34/44) of patients had resolution of the BBS (Table 3). The 7 patients

who failed therapy had biliary strictures resulting from CP (n Z 4), biliary stones (n Z 2), and primary sclerosing cholangitis (n Z 1); 5 of these patients underwent repeat stenting, and 2 improved without complete resolution. Technical difficulties during stent insertion included 2 stent deployments proximal to the distal stricture that had to be repositioned endoscopically.

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Fully covered SEMSs in benign biliary strictures

Complications associated with placement (14%) included post-ERCP pancreatitis (n Z 3, with 1 defined as severe by the consensus criteria22), pain (n Z 2), and postsphincterotomy bleeding (n Z 1). Complications associated with removal (9%) included post-ERCP pancreatitis (n Z 3) and pain (n Z 1). One patient had proximal biliary migration diagnosed at removal, and 1 patient had CSEMS duodenal migration with resolution of the stricture. One patient had stent occlusion on follow-up after 1 year. In one patient, the stent unraveled during removal; however, complete removal was accomplished without adverse effects (Table 3). Logistic regression analysis showed no factors potentially predictive of success (eg, age, sex, previous stenting, CSEMS length, and etiology).

DISCUSSION Of the nonsurgical approaches to treat BBS, plastic stents have become the most popular in most tertiary care centers. Several studies have reported high success rates with use of either single large5,6 or multiple7,8,10,23 plastic stents during repeat ERCP sessions. Their use appears to be limited in patients with CP.9,24,25 The success rate improves when larger-diameter stents are used10 and stent numbers are increased after each session26; however, durable stricture resolution typically requires multiple endoscopic sessions.25,26 Short-term patency of plastic stents has led some centers to consider metal stent placement.13-15 However, uncovered metal stents are associated with epithelial hyperplasia, leading to chronic inflammation of the bile duct and occlusion.10,27-30 To overcome the above drawbacks of uncovered metal stents, many investigators have studied covered metal stents in benign indications21,31,32 (Table 4). By using temporary placement of a partially covered metal stent, our group has previously demonstrated a success rate of 90% in a series of 79 patients.21 Stent migration was seen in 11 (14%) patients, whereas 6 (8%) patients had strictures related to mucosal hyperplasia at the level of the uncovered portion of the metal stent. On the basis of these data, a fully covered stent may eliminate the problem of epithelial hyperplasia and permit resolution of BBS with relatively fewer endoscopic sessions and with acceptable complication rates compared with plastic stent placement. The initial price of the CSEMS would be largely compensated by the reduction in the number of sessions required when plastic stents are used.33 Cahen et al34 recently published a case series of 6 patients with common bile duct strictures resulting from CP who were treated with fully covered metal stents (Hanaro, M.I. Tech, Seoul, South Korea). The stent was removed successfully in 4 of the 6 patients with a 66% resolution rate. In the first patient in whom stent removal 308 GASTROINTESTINAL ENDOSCOPY Volume 70, No. 2 : 2009

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was not possible, the distal end of the stent was cut off with argon to maintain its patency. In the second patient, plastic stents were placed through the metal stent to achieve drainage. One patient experienced stricture recurrence at 6 months and underwent hepaticojejunostomy. Our study investigates the application of a fully covered stent initially used in interventional radiology32 in treating BBS. It is made of nitinol and is covered by Gore-tex expanded polytetrafluoroethylene (W.L. Gore, Elkton, Md). It has flexible anchoring fins that were designed to prevent migration (Fig. 6). The intent-to-treat success rate in our study was 77%. Interestingly, 11 patients with BBS related to CP responded to treatment, with a success rate of 65% and an intent-to-treat result of 58% (Table 3). Compared with the other type of BBS, patients with CP seem more resistant to temporary placement of a covered metal stent, as previously demonstrated by our group.21 Although migration was only observed in 2 cases, these stents seemed to be associated with their own set of complications. Compared with the partially covered Wallstent (Boston Scientific, Natick, Mass), the Viabil CSEMS was more challenging to deploy because of its rigid delivery system. Removal was also problematic because of the anchoring fins, which caused ulceration and bleeding from the mucosa as the CSEMS was extracted, as confirmed by choledochoscopy in 19 patients and a subset of patients outside this study.35 The long-term consequences associated with those ulcerations still remain to be determined. In conclusion, the use of CSEMSs in patients with BBS remains to be further investigated. Its advantages over partially covered metal stents include elimination of epithelial hyperplasia and a decreased rate of migration. Its disadvantage is that removal can be difficult or problematic. Further studies need to be conducted, aimed at improving their removability and confirming their long-term efficacy.

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Received September 10, 2008. Accepted November 12, 2008. Current affiliations: Digestive Health Center (A.M., H.H., B.S., V.M.S., K.E., M.R., M.K.) and Department of Surgery (M.S.P., T.M.S.), University of Virginia Health System, Charlottesville, Virginia, USA. Presented as a poster at Digestive Disease Week 2008, San Diego, California (Gastrointest Endosc 2008;67:AB167). Reprint requests: Michel Kahaleh, MD, FASGE, Digestive Health Center Box 800708, University of Virgina Health System, Charlottesville, VA 229080708. If you want to chat with an author of this article, you may contact him at [email protected].

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