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    Endoscopic bilateral stent-in-stent placement for malignant hilar obstruction using a large cell type stent

    2016-12-12 05:46:54JinMyungParkSangHyubLeeKwangHyunChungDongKeeJangJiKonRyuYongTaeKimJaeMinLeeandWooHyunPaik

    Jin Myung Park, Sang Hyub Lee, Kwang Hyun Chung, Dong Kee Jang, Ji Kon Ryu, Yong-Tae Kim, Jae Min Lee and Woo Hyun Paik

    Seoul, Korea

    Endoscopic bilateral stent-in-stent placement for malignant hilar obstruction using a large cell type stent

    Jin Myung Park, Sang Hyub Lee, Kwang Hyun Chung, Dong Kee Jang, Ji Kon Ryu, Yong-Tae Kim, Jae Min Lee and Woo Hyun Paik

    Seoul, Korea

    BACKGROUND: Bilateral stent-in-stent (SIS) self-expandable metal stent placement is technically challenging for palliation of unresectable malignant hilar obstruction. In the SIS technique, the uniform large cell type biliary stent facilitates contralateral stent deployment through the mesh of the first metallic stent. This study aimed to assess the technical success and clinical effectiveness of this technique with a uniform large cell type biliary stent.

    METHODS: Thirty-one patients who underwent bilateral SIS placement using a large cell type stent were reviewed retrospectively. All patients showed malignant hilar obstruction (Bismuth types II, III, IV) with different etiologies.

    RESULTS: Sixteen (51.6%) patients were male. The mean age of the patients was 67.0±14.0 years. Most patients were diagnosed as having hilar cholangiocarcinoma (58.1%) and gallbladder cancer (29.0%). Technical success rate was 83.9%. Success was achieved more frequently in patients without masses obstructing the biliary confluence (MOC) than those with MOC (95.2% vs 60.0%, P=0.03). Functional success rate was 77.4%. Complications occurred in 29.0% of the patients. These tended to occur more frequently in patients with MOC (50.0% vs 19.0%, P=0.11). Median time to recurrent biliary obstruction was 188 days and median survival was 175 days.

    CONCLUSIONS: The large cell type stent can be used efficiently for bilateral SIS placement in malignant hilar obstruction. However, the risk of technical failure increases in patients with MOC, and caution is needed to prevent complications for these patients.

    (Hepatobiliary Pancreat Dis Int 2016;15:633-639)

    biliary tract disease;

    cholangiocarcinoma;

    endoscopic biliary drainage;

    stent insertion

    Introduction

    Malignant hilar obstructions are the result of cholangiocarcinoma or gallbladder cancer in most cases. The associated prognosis is poor and surgery provides the only chance for a cure.[1]However, nearly half of hilar cholangiocarcinoma cases are not candidates for curative resection owing to advanced disease or the presence of significant comorbidities.[2]Endoscopic stenting is commonly performed for palliation of malignant hilar obstruction. The choice between the self-expandable metal stent (SEMS) and plastic stent (PS) is still debatable. Theoretical advantages of SEMS include larger diameter, ability to drain side branches, and good conformability. A prospective study reported fewer adverse outcomes following SEMS deployment compared to PS recipients.[3]

    A recent retrospective study revealed that draining more than half of the liver volume, which frequently requires bilateral stent insertion, is an important predic-

    tor of effective drainage and is associated with a longer median survival in malignant hilar obstruction.[4]Bilateral SEMS placement can be performed by the sideby-side or stent-in-stent (SIS) method. The side-byside method is technically easier but can cause excessive expansion of the bile duct in the region of SEMS overlap. In a study comparing the two methods in bilateral endoscopic metal stenting, the incidence of adverse events was significantly higher for the side-by-side method.[5]In addition, reintervention can be difficult for stents placed side-by-side. Stents are often placed with complete intraductal positioning in this technique. If the distal ends of stents are not positioned next to each other, reintervention is difficult because each lumen cannot be individually cannulated with ease.[6]The SIS technique is free from these limitations. However, this method is technically more difficult; passing a guidewire and stent delivery system into a contralateral bile duct through the mesh of SEMS placed first is not easy. To overcome these difficulties, several newly designed SEMSs have been developed for bilateral SIS placement.[7-10]The Niti-S large cell D-type biliary stent (LCD; Taewoong, Seoul, Korea) has large cells (7 mm) that allow the passage of a second stent through the mesh, with the radial force maintained at the central portion of the stent because of its uniform cell size. The chain-like connection of each stent cell confers low axial force, which prevents bile duct kinking at both ends of the hilar stent.[7]In a prospective multicenter study using the LCD, bilateral SIS placement was technically successful in 25 (96%) of 26 patients in a single session. The final technical and functional success rates were 100% and 89%, respectively.[11]The study did not explored any factors related to technical success and no further study has been reported.

    The present study aimed to assess the high technical and functional success rates of LCD and investigated the factors related to technical success in bilateral SIS placement for malignant hilar obstruction.

    Methods

    Patients

    We retrospectively analyzed the endoscopic retrograde cholangiopancreatography (ERCP) prospectively maintained database of Seoul National University Hospital that contains information about consecutively enrolled patients. The patients who underwent bilateral SIS placement for malignant hilar obstruction between December 2011 and March 2014 were identified. Among them, those who underwent stent insertion using LCD were included in this study. The diagnosis of malignant hilar obstruction was made principally on the basis of computed tomography (CT) and/or magnetic resonance image (MRI), and was confirmed by pathologic examination. In our institution, endoscopic bilateral SIS placement is tried for all malignant hilar obstruction cases initially, unless the patient has comorbidities that preclude endoscopic procedures. If endoscopic procedure fails, percutaneous transhepatic biliary drainage (PTBD) is considered as rescue therapy. The study was approved by the Institutional Review Board of Seoul National University Hospital.

    Technique

    LCD has thick nitinol wires (0.203 mm) and the diameter of the stent delivery system is 8 Fr (Fig. 1). All patients underwent the procedures under conscious sedation with intravenous midazolam and meperidine. Standard duodenoscopes were used (TJF-240 and 260 V; Olympus, Tokyo, Japan), and an experienced pancreatobiliary endoscopist (Lee SH) carried out all of the procedures. An endoscopic biliary sphincterotomy was performed routinely, and two guidewires were placed through the hilar stricture into the left and right intrahepatic ducts. A 10-mm diameter LCD was used as the first or second stent; the stent was advanced over a guidewire inserted into the left hepatic duct and placed across the hilar stricture. After deployment of the first stent, the guidewire across the first stent was withdrawn and then inserted into the right hepatic duct via the mesh of the first stent. The other guidewire was used as a landmark and the second LCD was deployed over the reinserted guidewire. If it was difficult to insert the guidewire or second LCD into the undrained duct through the mesh of the first stent, the hilar stricture was dilated up to 6 or 8 mm using a Hurricane biliary balloon dilation catheter (Boston Scientific, Natick, MA, USA) prior to a second attempt of guidewire insertion or second LCD. If the second LCD insertion failed after balloon dilation, a HANAROSTENT (M. I. TECH, Seoul, Korea) or BONASTENT (Standard Sci-Tech, Seoul, Korea) having a slimmer delivery system (7 Fr) was used in place of the LCD. The procedure was performed under fluoroscopic guidance.

    Study outcomes and definition of events

    Fig. 1. Niti-S large cell D-type stent.

    Study outcomes were described according to a stan-

    dardized system for reporting biliary stents, the Tokyo criteria 2014.[12]Primary outcomes were technical success and LCD success rates. Secondary outcomes were functional success, complications, median time to recurrent biliary obstruction and overall survival. Technical success was designated as successful deployment of a SEMS in the intended location with sufficient coverage of the stricture. LCD success was defined as technical success using only LCDs (Fig. 2). Functional success was defined as reduction in serum bilirubin to normal value (≤1.2 mg/dL) or less than half of the pretreatment level. We assumed that masses obstructing the bile duct could disturb stent insertion. Therefore, CT and/or MRI findings were reviewed to check the presence of mass obstructing the biliary confluence (MOC). MOC was defined as a measurable mass that obstructed the confluence of the right and left intrahepatic ducts (Fig. 3). Intrahepatic and mass-forming hilar cholangiocarcinoma is MOC if the mass obstructs the confluence. Infiltrating hilar cholangiocarcinoma, without mass formation, is not MOC. Gallbladder cancer is MOC if the main mass obstructs the confluence. If the main mass is confined to the gallbladder and infiltrates to the confluence, gallbladder cancer is not MOC. Complications included pancreatitis, cholecystitis and cholangitis. Recurrent biliary obstruction was defined as a composite endpoint of either stent occlusion or migration, and time to recurrent biliary obstruction refers to the interval from SEMS placement to the recurrence of biliary obstruction. Death without recurrent biliary obstruction was treated as a censored case at the time of death.

    Fig. 2. Bilateral stent-in-stent placement.

    Fig. 3. A: A patient with mass obstructing the biliary confluence (MOC). Bilateral stent placement failed for the patient. B: A patient without MOC; periductal infiltrating tumor was observed. Bilateral stent placement was successful for the patient.

    Statistical analysis

    All statistical analyses were performed with SPSS 20.0 (SPSS, Chicago, IL, USA). Continuous variables were described by mean or median values. For reporting mean, the value of standard deviation (SD) was included, and median was reported with interquartile range (IQR). Categorical variables were given as counts and percentages. Median time to recurrent biliary obstruction and overall survival were assessed by the Kaplan-Meier method. Student’s t test or the Mann-Whitney U test was used to compare pairs of continuous variables, and the Fisher’s exact test was performed to compare categorical variables. A P value <0.05 was considered statistically significant.

    Results

    Clinical characteristics

    A total of 33 patients underwent endoscopic bilateral SIS placement for malignant hilar obstruction between December 2011 and March 2014, and 31 patients underwent the procedure with LCD. Table 1 summarizes their baseline characteristics. The mean age of the patients was 67.0±14.0 years. Most (51.6%) of the patients were male. Cholangiocarcinoma was detected in 58.1% of the patients, followed by gallbladder cancer in 29.0%, and metastatic cancer in 12.9%. According to the Bismuth classification, type IV was the most common type (48.4%), followed by type III (35.5%) and type II (16.1%). MOC was present in 32.3% (10/31) of the patients.

    Primary outcomes

    Technical success was observed in 26 of the 31 (83.9%) LCD patients. The first LCD was placed successfully in all 31 patients, and the second stent insertion failed in 5 pa-

    tients (Table 2); two patients failed because the guidewire could not be placed via the mesh of the first stent. They underwent PTBD as rescue therapy. The other three patients failed because the second stent and balloon dilation catheter could not be advanced through the first stent, although guidewire passage was successful (Table 3). One patient underwent subsequent PTBD. Among the 26 patients who achieved technical success, three received stents other than LCD as the second stent; accordingly, LCD success was achieved in 23 of the 31 patients (74.2%; Fig. 4). Technical success and LCD success were achieved in a single session. Technical success rate was higher in patients without MOC than in those with MOC (95.2% vs 60.0%, P=0.03).

    Secondary outcomes

    The secondary outcomes are summarized in Table 2. Functional recovery was noted in 24 (77.4%) of the 31 patients but failed in two patients after bilateral stent insertion. PTBD was performed for patients with persistent hyperbilirubinemia and cholangitis after stent placement. Of the patients, 29.0% had complications including cholangitis (22.6%), followed by pancreatitis (6.5%) and cholecystitis (3.2%). These complications were seen more frequently in patients with MOC, but there was no statistical significance (50.0% vs 19.0%, P=0.11). A 78-year-old man with MOC died of cholangitis and cholecystitis after failure of stent placement. He died after 12 days although PTBD and percutaneous cholecystostomy were performed. Stent occlusion developed in 12 (38.7%) patients. Endoscopic reintervention was successful in five patients. Metal stent was re-inserted in two patients and plastic stent was placed in another two patients. A patient underwent only sludge removal. PTBD was performed for the other seven patients. The median time to recurrent biliary obstruction was 188 days (IQR, 82-675 days; Fig. 5) and the median overall survival was 175 days (IQR, 57-343 days).

    Table 1. Clinical characteristics (n, %)

    Table 2. Primary and secondary outcomes

    Table 3. Details of technical failure

    Fig. 4. Patient cohort: bilateral stent-in-stent placement for malignant hilar obstruction using LCD between December 2011 and March 2014.

    Fig. 5. Kaplan-Meier curve showing time to recurrent biliary obstruction.

    Discussion

    Endoscope-mediated bilateral SEMS insertion is effective for palliation of biliary obstruction. The SIS method is physiologic and enables the insertion of a larger diameter SEMS compared to side-by-side placement. However, bilateral SIS placement is technically challenging when tried with conventional SEMS. Presently, bilateral SIS placement was technically successful in 83.9% of cases. If the analysis was confined to cases using only LCDs, the technical success rate was 74.2%.

    LCD reportedly can achieve a high technical success rate in patients with malignant hilar obstruction.[11]The final technical success rate of the study (100%) exceeded the rate in the present study. In the prior study, the procedure was retried the following day when the second stent delivery through the first stent was unsuccessful. Presently, the strategy was to use different kinds of stents in place of LCD. Direct comparison between the two studies is hindered by differences in the study designs. Nonetheless, the technical success rate using only LCDs in a single session in the prior study (96.2%) exceeded the present rate of 74.2%. The reason for the difference is uncertain. Cholangiocarcinoma and gallbladder cancer comprised most cases in both studies. Mean total bilirubin levels in the prior study (7.3 mg/dL) and current study (9.0 mg/dL) were comparable. Bismuth type II obstruction was more frequent (38.5%), and types III and IV obstruction was less frequent (23.1% and 38.5%) in the previous study than the present study (type II: 16.1%, type III: 35.5%, type IV: 48.4%). In our study, the technical success rate was 100% for type II cases and was lower in type III (81.8%) and IV (80.0%) cases, although the difference was not statistically significant. There is no evidence that Bismuth type II is more favorable than type III or IV in endoscopic bilateral stenting. One study[13]reported that percutaneous SEMS might be superior to endoscopic intervention in Bismuth type III and IV cases, although type II cases were not included.

    Presently, patients with MOC displayed a low technical success rate. To exclude the influence of confounding factors, baseline characteristics were compared between patients with and without MOC, and there was no statistically significant difference between the two groups. The presence of MOC could be a factor that preluded technical failure. In bilateral SIS placement, the guidewire and second stent should be advanced through the mesh of the first stent. It is not easy to pass the guidewire via the stent mesh and place it at the specific intrahepatic duct intended to drain. MOC can further complicate the procedure, because the guidewire should pass both the first stent mesh and the mass. Even if guidewire passage is successful, the advancement of the second stent can fail.

    MOC was present in about a third of patients in the current study. However, since the presence of masses was not reported in the previous LCD study,[11]it is not clear whether the presence of MOC induced the difference in technical success rates between studies. MOC may not be the main cause of the difference. Other factors like the different skills of the attending endoscopists and assistants could be influential. In the present study, the endoscopist and assistants were experienced and welltrained. They performed over 1000 ERCP procedures annually. In addition, the technical success rate in the first half of the patients (87.5%) was no lower than that of the second half patients (80.0%, P=0.34). Therefore, skills are likely not an explanation for the lower technical success rate (Table 2).

    Several prospective studies tested the usefulness of specially designed stents other than LCD for bilateral SIS placement. The reported technical success rates ranged from 85.3% to 95.2%,[8-10,14]with the technical success rates in a single session being 77%-78.6%.[9,10]These rates are comparable to those of the present study. Kawakubo et al[15]reported risk factors for technical failure in endoscopic bilateral SIS placement in a retrospective study. Metastatic disease was a significant risk factor for technical failure in their study, and the extrinsic nature of biliary stricture and requirement for multiple procedures were considered as causes of high technical failure in metastatic lesion. Our study showed similar outcomes. Technical failure tended to occur more frequently in metastasis than non-metastasis, although it was not statistically significant (P=0.11). Type II error cannot be ruled out because of a small number of metastasis cases (n=4) in our study.

    In patients who had failure of the second LCD placement after successful guidewire insertion, conventional stents were used instead of LCD. This strategy was suc-

    cessful in three of six patients. This can be explained by the difference of stent delivery systems. The LCD delivery system has a relatively large diameter (8 Fr), whereas conventional stents have delivery systems with a smaller diameter (7 Fr), which may facilitate the passage of stents through the mesh of the first stent. The same approach was tried elsewhere.[14]When the second stent could not be advanced along the guidewire, a different stent with a slimmer delivery system was used successfully in most patients. Kawakubo et al[15]suggested that SEMS with a large mesh and thin delivery system might be preferable to SEMS with a small mesh and thick delivery system in the subgroup analysis mentioned above, which supports the finding of our study. Although stents with a slimmer delivery system can be a solution to a failed second LCD placement, it cannot be used in case of guidewire insertion failure. In addition, no patients with MOC succeeded technically even after changing the second LCD to the conventional stent.

    The functional success rate (77.4%) in the current study was lower than that (89%) of the previous LCD study. The lower functional success rate reflects the lower technical success rate. With the exception of technical failure, the functional success rate was 92.3% in 24 of 26 patients. Although the definitions of functional success were heterogeneous, the functional success rates varied from 92.9% to 100% in patients who were technically successful in previous studies.[8-10,14,16]These results were comparable to ours.

    The early complication rate (29.0%) in the present study was about twice as high as that of the LCD study (15%).[11]However, the complication rate in patients without MOC was 19.0%, similar to the LCD study. Since the presence of masses was not reported in the LCD study, whether the presence of MOC induces the different rate of complications is not clear. In the present study, cholangitis was the most complication, which reflects the lower technical success rate. The drainage of contaminated bile duct was accentuated for cholangitis prevention as reported[17]which likely explains the relatively high complication rate in our study. Stent occlusion developed in about a third of patients in the present study. Since this was a retrospective study, the management of stent occlusion was not unified. About half of the patients underwent endoscopic reintervention and the remaining, PTBD. Therefore, comparison with the LCD study, in which endoscopic reintervention was performed for all stent occlusion cases,[11]is difficult. In 12 patients with stent occlusion, MOC was present initially in 3 patients, of whom one underwent endoscopic reintervention. Of the remaining 9 patients without MOC, four underwent endoscopic reintervention.

    The median time to recurrent biliary obstruction and overall survival (188 and 175 days, respectively) were comparable to those of the LCD study (157 and 220 days, respectively). The comparable median overall survival was explained by the similar patient composition. Unresectable cholangiocarcinoma and gallbladder cancer comprised most of the cases.[11]

    There are some limitations in our study. Firstly, selection bias may have been introduced due to the retrospective nature of the study. Secondly, the study was carried out at a single institution and all procedures were performed by one endoscopist. Therefore, our findings might not be generalizable. Further studies will be needed to validate our findings.

    In conclusion, LCD is efficiently used for bilateral SIS placement in patients with malignant hilar obstruction. However, the risk of technical failure increases in patients with MOC, and caution should be taken to prevent complications in these patients.

    Contributors: LSH proposed the study. PJM and LJM wrote the first draft. PJM, CKH and JDK collected and analyzed the data. RJK, KYT and PWH revised the article for important intellectual content. All authors contributed to the design and interpretation of the study and to further drafts. LSH is the guarantor.

    Funding: This study was supported by a grant from Daewoong Education Fund (800-20140081).

    Ethical approval: The study protocol was reviewed and approved by the Institutional Review Board of Seoul National University Hospital (H-1312-013-540).

    Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

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    8 Kim JY, Kang DH, Kim HW, Choi CW, Kim ID, Hwang JH, et al. Usefulness of slimmer and open-cell-design stents for endoscopic bilateral stenting and endoscopic revision in patients with hilar cholangiocarcinoma (with video). Gastrointest Endosc 2009;70:1109-1115.

    9 Park do H, Lee SS, Moon JH, Choi HJ, Cha SW, Kim JH, et al. Newly designed stent for endoscopic bilateral stent-in-stent placement of metallic stents in patients with malignant hilar biliary strictures: multicenter prospective feasibility study (with videos). Gastrointest Endosc 2009;69:1357-1360.

    10 Lee TH, Moon JH, Kim JH, Park DH, Lee SS, Choi HJ, et al. Primary and revision efficacy of cross-wired metallic stents for endoscopic bilateral stent-in-stent placement in malignant hilar biliary strictures. Endoscopy 2013;45:106-113.

    11 Kogure H, Isayama H, Nakai Y, Tsujino T, Matsubara S, Yashima Y, et al. High single-session success rate of endoscopic bilateral stent-in-stent placement with modified large cell Niti-S stents for malignant hilar biliary obstruction. Dig Endosc 2014;26:93-99.

    12 Isayama H, Hamada T, Yasuda I, Itoi T, Ryozawa S, Nakai Y, et al. TOKYO criteria 2014 for transpapillary biliary stenting. Dig Endosc 2015;27:259-264.

    13 Paik WH, Park YS, Hwang JH, Lee SH, Yoon CJ, Kang SG, et al. Palliative treatment with self-expandable metallic stents in patients with advanced type III or IV hilar cholangiocarcinoma: a percutaneous versus endoscopic approach. Gastrointest Endosc 2009;69:55-62.

    14 Hwang JC, Kim JH, Lim SG, Kim SS, Yoo BM, Cho SW. Y-shaped endoscopic bilateral metal stent placement for malignant hilar biliary obstruction: prospective long-term study. Scand J Gastroenterol 2011;46:326-332.

    15 Kawakubo K, Kawakami H, Toyokawa Y, Otani K, Kuwatani M, Abe Y, et al. Risk factors for technical failure of endoscopic double self-expandable metallic stent placement by partial stent-in-stent method. J Hepatobiliary Pancreat Sci 2015;22:79-85.

    16 Kawamoto H, Tsutsumi K, Harada R, Fujii M, Kato H, Hirao K, et al. Endoscopic deployment of multiple JOSTENT SelfX is effective and safe in treatment of malignant hilar biliary strictures. Clin Gastroenterol Hepatol 2008;6:401-408.

    17 De Palma GD, Pezzullo A, Rega M, Persico M, Patrone F, Mastantuono L, et al. Unilateral placement of metallic stents for malignant hilar obstruction: a prospective study. Gastrointest Endosc 2003;58:50-53.

    Received November 2, 2015

    Accepted after revision March 24, 2016

    Author Affiliations: Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea (Park JM, Lee SH, Chung KH, Jang DK, Ryu JK and Kim YT); Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea (Park JM); Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Korea (Lee JM); Department of Internal Medicine, Inje University Ilsan Paik Hospital, Koyang, Korea (Paik WH)

    Sang Hyub Lee, MD, PhD, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea (Tel: +82-2-2072-4892; Fax: +82-2-762-9662; Email: gidoctor@snuh.org) ? 2016, Hepatobiliary Pancreat Dis Int. All rights reserved.

    10.1016/S1499-3872(16)60107-8

    Published online June 7, 2016.

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