Endoscopic Deployment of Multiple JOSTENT SelfX Is Effective and Safe in Treatment of Malignant Hilar Biliary Strictures

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1 CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6: ENDOSCOPY CORNER Endoscopic Deployment of Multiple JOSTENT SelfX Is Effective and Safe in Treatment of Malignant Hilar Biliary Strictures HIROFUMI KAWAMOTO, KOICHIRO TSUTSUMI, RYO HARADA, MASAKUNI FUJII, HIRONARI KATO, KEN HIRAO, NAOKO KURIHARA, TAKASHI NAKANISHI, OSAMU MIZUNO, ETSUJI ISHIDA, TSUNEYOSHI OGAWA, HIROTOSHI FUKATSU, and KOHSAKU SAKAGUCHI Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama City, Japan Background & Aims: For the treatment of unresectable biliary tract carcinoma with hilar biliary stricture, antitumor therapy and biliary stenting should be addressed in terms of prolonged survival with a good quality of life. However, the endoscopic management of malignant hilar biliary strictures is difficult even for an expert endoscopist. We evaluated the efficacy and safety of the endoscopic deployment of multiple JOSTENT SelfX units in patients with hilar biliary strictures treated with or without chemotherapy. Methods: Between November 2003 and December 2006, endoscopic deployment of multiple JOSTENT SelfX units in hilar biliary strictures by using a partial stent-in-stent procedure was performed on 41 consecutive patients with primary cholangiocarcinoma (n 34) and gallbladder carcinoma (n 7) at a gastroenterologic center of Okayama University Hospital. Thirty-three patients were treated with gemcitabine (n 25) or S-1 (n 8). Results: Metallic stent deployment was successfully accomplished in all cases via only endoscopic procedures. During the follow-up period (mean, 210 days), mean patency time was 150 days, and metallic stent obstruction occurred in 15 cases (37%). Although a repeat intervention was required in all metallic stent obstructed cases, the deployment of the second metallic or plastic stent was completed successfully. The remaining 26 cases (63%) required no interventions. The median overall survival period was only 235 days. However, that of the patients receiving chemotherapy was 392 days. Conclusions: Endoscopic partial stent-in-stent deployment with multiple JOSTENT SelfX prostheses is effective and safe for the treatment of malignant hilar biliary stricture even in patients receiving chemotherapy. Biliary tract carcinoma, including cholangiocarcinoma and gallbladder carcinoma, often accompanies a hilar biliary stenosis. The curable treatment for these diseases is a complete resection. However, more than 50% of patients present at an advanced stage. Therefore, surgical treatment is not suitable for those patients. Although biliary stenting is offered to nonresectable cases, their prognosis is still grim. Photodynamic therapy (PDT) has been reported as an effective adjunctive therapy in unresectable cholangiocarcinoma. 1 However, PDT is available at only a limited number of tertiary centers, because special facilities are necessary to undertake this therapy. Therefore, for treatments of biliary tract carcinoma other than surgery, biliary stenting is essential at most hospitals. The endoscopic deployment of a metallic stent (MS) in patients with unresectable malignant biliary strictures can provide good palliation to these patients as a result of their efficacy, low incidence of complications, and patient acceptance. 2 7 However, the treatment of hilar biliary strictures with an MS remains controversial. One reason for this is that MS deployment into more than 2 segments in the liver is thought to be technically demanding. 8,9 The JOSTENT SelfX stent (Abbott Vascular Devices, Redwood City, CA) is manufactured from a nickel-titanium alloy (nitinol). It exhibits a high degree of flexibility and elasticity and also offers a wide stent mesh, a thin delivery shaft (7F), and good pushability. According to May and Ell, 10 who reported the first preliminary results on the JOSTENT SelfX, the primary advantage of this stent lies in its minimal shortening, compared with the Wallstent (Schneider, Bulach, Switzerland/Boston Scientific Microvasive, Natick, MA). Furthermore, this stent is available for multiple stenting in high-grade hilar biliary strictures Recently, effective chemotherapeutic agents such as gemcitabine have been described in a few articles on the treatment of biliary tract carcinoma Adjunctive therapy for the patients with malignant hilar biliary strictures is mentioned in association with cholangitis, which should be prevented by appropriate biliary stenting. 17 For these reasons, we conducted this retrospective study to evaluate the feasibility, efficacy, and safety of multiple stenting with the JOSTENT SelfX MS for the treatment of hilar biliary strictures. Patients and Methods Patients Forty-one consecutive patients with malignant hilar biliary strictures caused by unresectable biliary tract carci- Abbreviations used in this paper: CI, confidence interval; CR, complete response; CT, computed tomography; MS, metallic stent; MST, median survival time; PD, progression of disease; PDT, photodynamic therapy; PR, partial response; SD, stable disease by the AGA Institute /08/$34.00 doi: /j.cgh

2 402 KAWAMOTO ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 4 noma who were treated between November 2003 and December 2006 were eligible for this study. The surviving patients (n 11) were followed up until June Patients with hilar biliary strictures caused by other reasons than biliary tract tumors were excluded. The patient demographic data are presented in Table 1. All patients had more than 2 JOSTENT SelfX units deployed via the endoscopic retrograde route. Written informed consent was obtained from all patients, and our ethical committee approved this study. The types of hilar bile duct stricture, classified according to the Bismuth classification, 18 were as follows: type II (n 5); type IIIa (n 3); and type IV (n 33). Patient diagnosis was made principally via imaging modalities such as ultrasonography, computed tomography (CT), magnetic resonance imaging including magnetic resonance cholangiopancreatography, and endoscopic retrograde cholangiopancreatography. Histologic or cytologic confirmation of malignancy was performed on all patients. Before stenting, 25 patients (61%) were subjected to endoscopic biliary drainage by using conventional stents or a nasobiliary drain to relieve jaundice and cholangitis or to confirm the diagnosis. These patients were subjected to stenting, at most 3 weeks after endoscopic biliary drainage. After stent deployment, 33 patients (80%) received chemotherapy with either gemcitabine (n 25; mg/m 2 / wk, weekly for 3 of every 4 weeks) or S-1 (an oral fluorouracil antitumor drug that combines 3 pharmacologic agents: tegafur, which is a prodrug of 5-fluorouracil; 5-chloro-2,4-dihydroxypyridine, which inhibits dihydropyrimidine dehydrogenase activity; and potassium oxonate, which reduces gastrointestinal toxicity; n 8; 80 mg/body/day, for 2 of every 3 weeks). Responses to chemotherapy were assessed according to the World Health Organization criteria. Two-dimensional measurable lesions of each tumor were reevaluated via abdominal CT regularly after every 2 months. Aphysician and a radiologist reviewed the CT films independently and assessed the response. A complete response (CR) was defined as the complete disappearance of all evidence of the tumor. A partial response (PR) was defined as a 50% decrease in tumor size in all indicator lesions. Stable disease (SD) was defined as a 50% decrease or a 25% increase in tumor size in all indicator lesions. Progression disease (PD) was defined as a 25% increase of tumor size in any measurable lesion or the development of any new lesions. For patients with bile duct lesions only, it is impossible to evaluate the lesion after MS deployment. For such cases, the term NE, not evaluated, was applied. Cases with CR, PR, or SD were required to maintain the evaluation for at least 4 consecutive weeks, without evidence of disease progression. Therefore, in cases of CR, PR, or SD, a secondary assessment via an imaging study was required. Figure 1. Picture of the JOSTENT SelfX. Table 1. Baseline Clinical Data No. of patients 41 Gender (M/F) 26/15 Mean age (y) (range) 68 (51 90) Diagnosis: Cholangiocacinoma 34 Gallbladder carcinoma 7 Presence of liver mass on imaging study 23 Bilirubin level (mg/dl) 6.7 ( ) Serum alkaline phosphate (IU/L) 1079 ( ) Mean follow-up time (days) 210 (27 997) Stent Material and Deployment Technique The JOSTENT SelfX is an uncovered MS made from nitinol. The unique character of this stent depends on its special configuration (Figure 1). This stent has 15 waveshaped struts at each circumference that do not cross. Because every fifth zigzag element is connected, only 3 are connected in a given circumference. As a result, this stent has high flexibility. When bending, the gap of the stent mesh becomes wider, and a Y-configuration deployment is easy to

3 April 2008 ENDOSCOPIC DEPLOYMENT OF MULTIPLE JOSTENT SELFX 403 Figure 2. Procedure for partial stent-in-stent deployment. Patient had type II stenosis, caused by cholangiocarcinoma. After passing a guidewire into the left hepatic duct, the right hepatic duct was sought with another guidewire (A). After dilating the stenotic lesion with a balloon dilator, the first JOSTENT SelfX was deployed from the left hepatic duct to the common bile duct. In (B), the guidewire in the right hepatic duct existed outside of the initially deployed JOSTENT SelfX, so that finding the branching point of the right hepatic duct with a guidewire through the mesh in the first JOSTENT SelfX was easy to achieve by using it as a landmark for branching. After passing a guidewire through the mesh into the right hepatic duct, the second JOSTENT SelfX was deployed in the partial stent-in-stent procedure (C). achieve. Because of these characteristics, this stent was used in this study. More than 2 JOSTENT SelfX units were deployed in the hilar bile ducts by using partial stent-in-stent procedures as described below. The stent size was 10 mm in diameter and 44, 68, or 92 mm in length. The endoscopes used for this procedure were the Olympus JF260V or TJF240 (Olympus, Tokyo, Japan) because of the large channels of these scopes (3.7 and 4.2 mm, respectively). Endoscopic therapy was conducted with patients under analgesic sedation (diazepam 5 10 mg and pethidine mg, IV). All patients were in the prone position throughout the procedure. To maximize visualization of the biliary confluence, the patients were transiently shifted to the right or left oblique position. The standard deployment technique adopted in this study is illustrated in Figure 2 and described briefly below. Following the repetition of deep cannulation into the common bile duct, 2 guidewires were inserted into the target hepatic ducts. When seeking the target hepatic duct, Linearguide (Olympus) or Radifocus (Terumo, Tokyo, Japan) was suitable. These guidewires were termed the seeking guidewires. After seeking the target hepatic duct, one guidewire was exchanged for a inch stiff-type Jagwire (Boston Scientific) or THSF (Wilson-Cook Medical Inc, Winston-Salem, NC). This inch guidewire was inserted into the hepatic duct in which the first JOSTENT SelfX was to be deployed. This guidewire was termed the leading guidewire. The other guidewire was exchanged for a inch Jagwire or Cheerleader (0.025-inch; Pyorax Japan, Yokohama, Japan). This guidewire was used as a landmark for the bifurcation of the common hepatic duct. This guidewire was therefore termed the landmark guidewire. Balloon dilatation with a Hurricane (8 mm in diameter and 4 cm in length; Boston Scientific Corp) or Maxpass (8 mm in diameter and 3 cm in length; Olympus) was applied for cases with a hard stricture. For cases with a Bismuth II stricture, balloon dilatation was not performed. In cases with Bismuth IIIa or IV stricture, it was performed on the branch in which the last MS was deployed. Because the resistance in advancing the last delivery device is very strong, it should be reduced via balloon dilatation before MS deployment. The first stent was usually inserted into the left hepatic duct over the leading guidewire. Before deployment of the second stent, seeking the next hepatic duct through the stent mesh with the seeking guidewire was easy as a result of the existence of the landmark guidewire. The second stent delivery device was deployed through the mesh via a partial stent-in-stent procedure, so that the 2 stents overlapped partially in the common hepatic duct and branched out in 2 directions, forming a Y-shape. Figure 3. This patient had cholangiocarcinoma in the left lobe of the liver. Because the liver parenchyma in the left lobe was replaced by the tumor, there was no necessity for stent deployment in the left hepatic duct (A). Right anterior and posterior hepatic ducts were stenosed separately by the tumor (B). Therefore, 2 JOSTENT SelfX stents were deployed in both right hepatic ducts via the partial stent-in-stent procedure (C).

4 404 KAWAMOTO ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 4 In the percutaneous procedure, tissue ingrowth was defined as the absence of opacity in a portion of the stent lumen, with no improvement after drainage. When the stent lumen became opacified after drainage and bile flow was resumed, the cause of stent obstruction was determined as debris or sludge. Figure 4. Three-branched partial stent-in-stent procedure with JOSTENT SelfX stents. Patient had cholangiocarcinoma with type IV hilar stricture (A). This patient had 3 JOSTENT SelfX stents inserted into the left lateral, right anterior, and right posterior segments, respectively (B). When the left lobe was occupied with a large tumor in patients with a Bismuth type IV stricture, the first stent was inserted into the posterior branch of the right hepatic duct. In such cases, a second stent was deployed in the right anterior branch (Figure 3). With further refinements in our technique, 3- or 4-branched partial stent-in-stent deployment was performed endoscopically in patients with a Bismuth type IIIa or IV stricture (Figures 4 and 5). The first stent was inserted into the left hepatic duct, the second into the posterior branch of the right hepatic duct, and the third into the right anterior branch A successful procedure was defined as the establishment of more than 2 branches in a partial stent-in-stent deployment in at least 2 of 3 segments, such as the left lateral, right anterior, or right posterior segments. We evaluated the success rate of stent deployment, the procedure time, short-term and longterm complications, and patency periods. To assess the influences of stenting, the serum total bilirubin and alkaline phosphatase values (normal range, IU/L) were also evaluated before the first biliary drainage and at 1 month after MS deployment. Stent Occlusion Stent obstruction was suspected in patients with increasing laboratory parameters for cholestasis, fever, and/or jaundice. The cause of stent obstruction was certified under an endoscopic examination or percutaneous transhepatic procedure. Intraductal ultrasonography was used to define the cause of obstruction, when an endoscopic examination was performed. Tissue ingrowth was defined as an echogenic soft tissue density in the stent lumen that failed to disappear after intraductal movement of the retrieval balloon. Tissue overgrowth was also defined as an echogenic soft tissue density over the stent lumen. If the echogenic tissue was made to disappear by the retrieval balloon under intraductal ultrasonography, sludge or debris was determined as the cause of stent obstruction. In this case, debris or sludge appeared from the duodenal papilla. Reintervention When the lumen of the inserted MS was obstructed, reintervention was performed via either a percutaneous or endoscopic procedure. Percutaneous procedures were performed on the first 2 cases. Via the right and left routes, 2 JOSTENT SelfX stents were inserted into the bilateral lobes via the partial stent-in-stent procedure through the previously deployed JOSTENT SelfX. Endoscopic procedures were performed on the remaining patients. In consideration of a second reintervention and the procedure cost, we inserted 7F plastic stents (Zimmon-type ERBD stent; Wilson-Cook Medical Inc, or Flexima; Boston Scientific Corp) into 1, 2, or 3 lobes through the lumen of the previously deployed JOSTENT SelfX. The guidewires and catheters used in seeking the obstructed lumen of the stent were the same as those used in the endoscopic deployment of the JOSTENT SelfX. When the cause of stent obstruction was sludge, the removal of the sludge was performed endoscopically. A retrieval balloon catheter (Multi-3V Extraction Balloon, proximal injection type; Olympus) was used. The sludge was removed via the pullmotion of the inflated balloon catheter or washed out via saline injection. Statistical Analysis Statistical analysis of patient data and clinical parameters was conducted by using median and range. Analysis of MS patency and patient s survival was performed with Kaplan- Meier curves. Survival was defined as the time from MS deployment to death or the last date of last follow-up evaluation (June 30, 2007). The Wilcoxon signed rank test was used to compare the laboratory data before and after MS deployment. The Cox Figure 5. Four-branched partial stent-in-stent procedure with JOSTENT SelfX stents. Patient had cholangiocarcinoma with type IV hilar stricture (A). This patient had 4 JOSTENT SelfX stents inserted into the left lateral, S5 and S8 of the right anterior, and right posterior segments, respectively (B).

5 April 2008 ENDOSCOPIC DEPLOYMENT OF MULTIPLE JOSTENT SELFX 405 proportional hazards models were used to predict mortality or shorter survival. Clinically important variables and those found to be statistically significant by univariate analysis were considered as candidate variables for the multivariate model. A P value of less than.05 was considered statistically significant. All analyses were performed with Statistical Analysis System software, version 8 (SAS Institute, Inc, Cary, NC). Results The overall success rate for multiple MS deployment was 100% (41/41). There was no patient in this study period for whom endoscopic retrograde cholangiopancreatography was unsuccessful. As a result, no patients were referred for percutaneous transhepatic biliary drainage. The relationship between the number of branches and the type of stenosis is illustrated in Table 2. The mean procedure time was 55 minutes (range, minutes). No patient acquired cholangitis needing additional drainage immediately after the procedure. After MS deployment, the laboratory data were not aggravated in most patients. The mean bilirubin level decreased significantly from 6.7 mg/dl (range, ) to 0.8 mg/dl (range, ) (P.01). The mean alkaline phosphatase level also decreased significantly from 1079 IU/L (range, ) to 698 IU/L (range, ) (P.01). There were 2 patients whose bilirubin levels increased, although in each case, the deviation was within 0.3 mg/dl. The bilirubin level of each of these patients was also less than 1.6 mg/dl. On the other hand, there were 8 patients whose alkaline phosphatase levels increased. The mean follow-up period for these patients was 247 days (range, days). During this period, 3 patients presented with an obstructed MS (days 54, 226, and 263, respectively). After MS deployment, 38 of 41 patients (93%) could be discharged from our hospital. The remaining 3 patients (7%) could not be discharged as a result of progression of the primary disease. Within 30 days after MS deployment, incidents of both acute cholecystitis (n 3, 7%) and liver abscess (n 1, 2%) occurred. Both conditions were treated by percutaneous transhepatic drainage, and successful recovery from morbidity was achieved in these patients. The cumulative patency curve is illustrated in Figure 6. The mean patency time of the JOSTENT SelfX was 150 days. During this period, stent obstruction occurred in 15 cases (37%). All patients with stent occlusion presented with cholangitis and required hospitalization. Therefore, all of these patients were treated as inpatients. The median patency time in the MSobstructed cases was only 84 days (range, days). Eight of these cases (53%) developed stent obstruction within 3 months. The cause of stent obstruction was certified under endoscopic Figure 6. Cumulative patency curve of the JOSTENT SelfX, assessed via the Kaplan-Meier method. examination (n 13) or percutaneous transhepatic procedure (n 2). The causes of stent obstruction were tissue ingrowth (n 10), sludge (n 4), and tissue overgrowth (n 1). Eleven patients had plastic stents inserted endoscopically. Two patients received endoscopic MS cleaning. Two patients received MS redeployment via the percutaneous route. As a result of these procedures, 14 of 15 patients (93%) successfully recovered from the first MS obstruction. In these patients, the median number of sessions required after the first MS placement was 2 (range, 1 8). On the other hand, the remaining 26 patients (63%) required no repeat interventions. Thirty-three patients received chemotherapy with gemcitabine or S-1. Six cases had lesions that could not be evaluated after MS deployment. Therefore, the remaining 27 patients were available for evaluation. All patients received at least 2 cycles of therapy. Three patients (11%) achieved PR. Ten were evaluated as SD (37%) and 14 as PD (52%) despite chemotherapy. The overall response was therefore 11%. Of the 41 study patients, 30 patients died as a result of progressive disease. The cumulative survival curve for all patients is illustrated in Figure 7. The median survival time (MST) was 235 days (interquartile range, ). The 1-year survival rate after MS deployment was 41%. Table 3 shows the results of the univariate analysis for all variables considered. Chemotherapy was a statistically significant predictor in the univariate analysis (hazard ratio, 0.28; 95% confidence interval [CI], ; P.027). Age was also associated with poor survival. However, in the multivariate analysis, only chemotherapy was a statistically significant Table 2. Number of MS Branches According to Type of Stenosis Number of MS branches Type of stenosis Two Three Four Total II IIIa IV Total Figure 7. Kaplan-Meier curve of overall survival after multiple deployment of JOSTENT SelfX.

6 406 KAWAMOTO ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 4 Table 3. Results of Univariate Analysis of All Prognostic Factors Considered Variable Hazard ratio (95% CI) P value Age 2.02 ( ).130 Gender 1.41 ( ).423 Presence of liver mass on imaging 1.77 ( ).183 study Chemotherapy 0.28 ( ).027 Bismuth classification 0.73 ( ).610 Pretreatment bilirubin level 0.87 ( ).753 Reobstruction of MS 1.02 ( ).973 predictor of long survival after MS deployment (hazard ratio, 0.19; 95%CI, ; P.008) (Table 4). The MST of the chemotherapy-receiving patients was 392 days (interquartile range, ) (Figure 8). Discussion Endoscopic palliation of malignant hilar biliary strictures often presents complex problems. First, the deployment of more than 2 MSs in a hilar biliary stricture is often technically demanding, even for an expert endoscopist. Second, a high rate of complications and technical failure is sometimes associated with the endoscopic approach. 19,20 In any case, a favorable outcome can be achieved with a combination of appropriate patient selection and well-suited management of the hilar biliary stricture. Thus far, palliative biliary stenting has been the only option for the treatment of patients with unresectable biliary carcinoma as a result of the grim prognosis of these patients. In this study, the overall MST was 235 days. However, that of the patients who received chemotherapy was improved significantly (392 days; hazard ratio 0.29; 95% CI, ; P.037). Recently, PDT has been reported as an important adjunctive therapy in cholangiocarcinoma One retrospective study and 2 randomized controlled trials have been reported in the literature. Their MST values were 344 days, 493 days, and 630 days, respectively. Although our study included patients with gallbladder carcinoma, the value of our study overlaps with those of these 3 studies. This strongly suggests that the chemotherapy of biliary tract carcinoma with multiple MSs can become an alternative therapy, although the response rate was not satisfactory in this study. However, if a more effective chemotherapy were introduced, the advantages of this therapy would be considerable. PDT is offered at very few tertiary centers in Japan, similar to the United States. Given that endoscopists can manage the deployment of multiple MSs, this therapy might become widely available. Table 4. Results of Multivariate Analysis of Prognostic Factors Variable Hazard ratio (95% CI) P value Age 1.43 ( ).546 Presence of liver mass on imaging 1.99 ( ).115 study Chemotherapy 0.19 ( ).008 Figure 8. Kaplan-Meier curve of survival in patients receiving chemotherapy after multiple deployment of the JOSTENT SelfX. Furthermore, PDT generally requires plastic stents. Consequently, stent occlusion caused by sludge formation is unavoidable at some point in the patients course. Because stent occlusion is associated with life-threatening complications (eg, cholangitis), patients with plastic stents require repeat interventions and exchanges. In this study, patients who presented no MS obstruction required no repeat intervention during their lifetime. The proportion of the patients was 63% (26/41), a rate that is not achieved via PDT plus plastic stents. This result indicates that chemotherapy plus MSs presents an advantage associated with a quality of life issue. The combination of chemotherapy and PDT for cholangiocarcinoma might be promising, because the nature of chemotherapy is systemic and that of PDT is regional. However, in this situation, the partial stent-in-stent deployment of MSs cannot be indicated. Because the structure of the metal fibers at the hilar portion is complicated, laser fibers become caught in the metal fibers, leading to fiber fracture. 21 In this study, we adopted the partial stent-in-stent procedure for the deployment of multiple MSs into hilar biliary strictures. Via this procedure, the stricture from the hilus to the common hepatic or bile duct is expanded by the overlapped MS. As a result, the stricture is not excessively expanded, as in the parallel deployment of multiple MSs. In addition, the entire length of the stricture is continuously expanded by the multiple MSs. Thus, the partial stent-in-stent deployment is an ideal procedure for the treatment of hilar biliary strictures. In this study, we succeeded in this procedure in 41 consecutive patients. However, there might be some patients whose biliary strictures are not amenable to this procedure in the future. It is well-known that a single MS can often manage jaundice or cholangitis It is certain that multiple MS deployment is not necessary in all patients with malignant hilar biliary stricture. Supporters of single lobe drainage expect the lower risk of complications associated with multiple MS deployment. In addition, adequate palliation can be achieved by the drainage of only 25% of the liver. 27 Therefore, single MS deployment is sufficient for survival in most patients with hilar strictures. However, no prospective study has appeared regarding the advantages of having one versus several MSs in patients with unresectable hilar neoplasms. In one retrospective study of endoscopic MS deployment, the disadvantage of unilateral stent deployment was described for patients with Bismuth III strictures with both lobes opacified. 28 In one retrospective study

7 April 2008 ENDOSCOPIC DEPLOYMENT OF MULTIPLE JOSTENT SELFX 407 of percutaneous MS deployment, the necessity of the deployment of 2 stents was mentioned in patients with Bismuth IV strictures. 29 Accordingly, we regard the necessity or non-necessity of more than 2 MSs at the hilar stricture as dependent on patient condition or additional therapy. To avoid cholangitis in the course of chemotherapy and to preserve the functional volume of the liver as much as possible, we regard multiple stenting as a reasonable option. Therefore, we consider that it is meaningful to possess the skills to provide this treatment to patients with hilar biliary strictures. However, we could not determine whether the patients needed more than 1 stent to relieve jaundice, and whether this led to more or fewer complications than the placement of 1 or 2 stents, as a result of the retrospective nature of this study. To conduct the procedure successfully, we highlighted the selection of guidewires according to purpose, such as seeking a target hepatic duct, thereby marking the bifurcation and leading a stent-mounted delivery device to the target lesion. Although this method increases guidewire cost, it is impossible to satisfy the conflicting guidewire requirements with 1 guidewire. For example, the seeking guidewire demands pliability, whereas the leading guidewire demands stiffness. Although the technical advancement of these devices might overcome this problem in the future, at present, it is necessary to make full use of the several kinds of available guidewires in accordance with their qualities. In this study, MS obstruction occurred in 15 cases. Most of these cases recovered from morbidity with the second intervention. Therefore, we believe that the multiple stenting used in this study will not be harmful to the patients. However, according to the Kaplan-Meier curve, a portion of the patients (less than 30%) had stent obstruction within 3 months. This indicates that there are some patients who are not suitable for MS deployment in light of the cost. In this study, we could not elucidate what parameters would affect stent patency as a result of the small number of cases. A further study will clarify the inclusion criteria for multiple stenting for hilar biliary strictures. In conclusion, because of the high success rate, low incidence of morbidity, and good recovery after obstruction observed in this study, the JOSTENT SelfX is regarded to be a safe and suitable MS for use in the treatment of hilar biliary stricture, even in patients receiving chemotherapy. References 1. Wiedmann M, Caca K, Berr F, et al. Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma: a phase II pilot study. Cancer 2003;97; Vitale GC, Larson GM, George M, et al. 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8 408 KAWAMOTO ET AL CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No Palma G, Pezzullo A, Rega M, et al. Unilateral placement of metallic stents for malignant hilar obstruction: a prospective study. Gastrointest Endosc 2003;58: Adam A. Metallic biliary endoprostheses. Cardiovasc Intervent Radiol 1994;17: Chang WH, Kortan P, Haber GB. Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage. Gastrointest Endosc 1998;47: Inal M, Akgul E, Aksungur E, et al. Percutaneous placement of biliary metallic stents in patients with malignant hilar obstruction: unilobar versus bilobar drainage. J Vasc Interv Radiol 2003;14: Address requests for reprints to: Hirofumi Kawamoto, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho, Okayama City ,Japan. h-kawamo@md.okayama-u.ac.jp;fax: This study was funded in part by a grant from Abbott Vascular Devices, Redwood City, California.