11.5-Fr Large bore plastic stents versus fully covered self-expandable metallic stents for the management of preoperative endoscopic biliary obstruction in pancreatic cancer: a multicenter retrospective cohort study

11.5-Fr Large bore plastic stents versus fully covered self-expandable metallic stents for the management of preoperative endoscopic biliary obstruction in pancreatic cancer: a multicenter retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article 11.5-Fr Large bore plastic stents versus fully covered self-expandable metallic stents for the management of preoperative endoscopic biliary obstruction in pancreatic cancer: a multicenter retrospective cohort study Akinori Maruta, Takuya Koizumi, Kota Shimojo, Yosuke Ohashi, Shota Iwata, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9383752/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background Self-expandable metallic stents (SEMS) are recommended for preoperative biliary drainage in patients with pancreatic cancer. However, they are associated with a relatively high incidence of non-recurrent biliary obstruction (RBO) adverse events (AEs), such as pancreatitis and cholecystitis. The 11.5-Fr large-bore plastic stent (LBPS) is a newly developed stent with a larger diameter than conventional plastic stents. The aim of the present study was to compare the clinical outcomes of LBPS and SEMS in preoperative biliary drainage for pancreatic cancer. Methods We retrospectively evaluated 80 patients who underwent preoperative biliary drainage for pancreatic cancer between January 2011 and December 2025. Patients were divided into the LBPS and SEMS groups according to the stent placed. Results RBO occurred in 20.0% and 25.0% of patients in the LBPS and SEMS groups, respectively, with no significant difference in the time to RBO between the groups. Pancreatitis and cholecystitis were observed in 0% versus 18.3%, and 0% versus 8.3% of patients in the LBPS and SEMS groups, respectively. Conclusion The 11.5-Fr LBPS demonstrated patency equivalent to that of SEMS and was associated with a low incidence of non-RBO AEs. Therefore, LBPS may become a preferred option for preoperative biliary drainage in pancreatic cancer. large bore plastic stent preoperative biliary drainage pancreatic cancer self-expandable metallic stent recurrent biliary obstruction Figures Figure 1 Figure 2 Figure 3 Introduction Pancreatic cancer often causes obstructive jaundice, for which endoscopic biliary drainage using endoscopic retrograde cholangiopancreatography (ERCP) is the treatment of choice. Plastic stents (PS) have traditionally been used for preoperative biliary drainage in patients with pancreatic cancer. The advantages of PS include their relative ease of placement, ability to be replaced and removed, and low cost. In recent years, however, preoperative neoadjuvant chemotherapy (NAC) has become the standard treatment, resulting in a longer preoperative waiting period compared with conventional upfront surgery ( 1 – 5 ). Given this extended waiting period associated with NAC, the patency of PS is often insufficient, and the European Society of Gastrointestinal Endoscopy (ESGE) guidelines therefore recommend a 10-mm self-expandable metallic stent (SEMS) for preoperative drainage ( 6 ). Although SEMS have a large caliber and are expected to prolong patency, they have been reported to be associated with a high incidence of non-recurrent biliary obstruction (RBO)-related adverse events (AEs), such as pancreatitis and cholecystitis ( 7 – 9 ). These AEs raise concerns regarding potential discontinuation of NAC or postponement of surgery. Furthermore, evidence regarding the effects of SEMS on surgical outcomes remains limited. In contrast, the 11.5-Fr large-bore plastic stent (LBPS) (Oasis® One Action Stent Introduction System Preloaded with Cotton-Leung® Biliary Stent, Cook Medical Japan G.K.) is a newly developed stent with a larger diameter than conventional PS and three drainage lumens at the tip. Notably, the side holes are larger than those of conventional stents, suggesting improved drainage efficacy (Fig. 1 a. b ). The purpose of this study was to compare the clinical outcomes of LBPS and SEMS in preoperative biliary drainage for pancreatic cancer. Patients and Methods Patients’ selection This retrospective cohort study was conducted at four tertiary care centers: Gifu University Hospital, Gifu Prefectural General Medical Center, Gifu Municipal Hospital, and Matsunami General Hospital. A database, which encompassing all patients who were histologically diagnosed with pancreatic cancer between January 2011 and December 2025, was analyzed to identify those who met the following inclusion criteria: ( 1 ) pathologically comfirmed pancreatic cancer classified as resectable or borderline resectable based on computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasound-guided fine needle aspiration or biopsy (EUS-FNA/FNB); ( 2 ) underwent preoperative biliary drainage for obstructive jaundice due to pancreatic cancer using either LBPS or 8-12mm fully covered self-expandable metallic stent (FCSEMS); and ( 3 ) age older than 20 years. Patients were excluded if they met any of the following exclusion criteria: ( 1 ) biliary drainage with PS smaller than 11.5-Fr LBPS, ( 2 ) biliary drainage performed using percutaneous transhepatic biliary drainage (PTBD) or endoscopic ultrasound-guided biliary drainage (EUS-BD), except for the rendezvous technique; ( 3 ) coexisting malignant biliary obstruction involving the hilar part of the biliary system, defined as within 2 cm below the biliary confluence; ( 4 ) biliary drainage performed at other institutions; ( 5 ) a prior history of surgical biliary reconstruction; or ( 6 ) adverse events (AEs), such as hemorrhage or perforation, occurring before stent deployment. Patients deemed ineligible for the study by the principal investigator and those who declined participation based on publicly available information were also excluded. Pancreatic cancer staging was performed according to the Union for International Cancer Control ( UICC) criteria ( 10 ). Resectability was determined based on the clinical practice guidelines for pancreatic cancer issued by the Japan Pancreas Society ( 11 , 12 ). Patients were divided into the LBPS and SEMS groups according to the type of stent used. Written informed consent was obtained from all patients prior to the procedures, and consent for the use of research data was obtained on an opt-out basis. All procedures in this study were conducted in accordance with the ethical standards of the institutional and national research committees and the principles of the 1964 Helsinki Declaration and its later amendments. The study protocol was approved by the Institutional Review Board of each participating institution (Gifu University Hospital: 2025 − 359) and was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN: 60443). Endoscopic Procedures All ERCP procedure were performed using a standard duodenoscope (TJF-260V, JF-260V, or JF-240; Olympus, Tokyo, Japan) under conscious sedation with midazolam and pentazocine, with continuous monitoring of vital signs. Bile duct cannulation was performed using a wire-loaded cannulation technique. If biliary cannulation was difficult with the standard approach, the pancreatic guidewire technique or pre-cutting was applied as needed. After successful selective bile duct cannulation, cholangiography was performed to evaluate the location and length of the malignant biliary obstruction. Endoscopic sphincterotomy (EST) or two-step drainage using endoscopic nasobiliary drainage (ENBD) was performed at the operator’s discretion. EST was performed using a papillotome (KD-211Q-0725 or KD-V411M-0725; Olympus, Tokyo, Japan, or Correctome; Boston Scientific, Massachusetts, USA) over a guidewire. A stent of sufficient length to cover both the obstruction and the duodenal papilla was selected for biliary drainage. Subsequently, a FCSEMS (8–12 mm in diameter and 5–8 cm in length) or LBPS (11.5-Fr and 5–8 cm in length) was deployed at the obstruction site. The diameter, length, and type of stent were chosen at the discretion of each endoscopist. Antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and protease inhibitors were administered before or after ERCP according to institutional protocols. Neoadjuvant Chemotherapy After proper biliary drainage and improvement of liver function, NAC was performed in some patients. The regimens used were S-1, gemcitabine plus S-1, gemcitabine plus nab-paclitaxel, or FOLFIRINOX according to the discretion of each hospital. Contrast-enhanced CT or MRI is generally performed for restaging after the completion of NAC. The final decision to perform surgical exploration was made by an expert panel of endoscopists, surgeons, and radiologists. Surgical resection The standard surgical procedures included pylorus-preserving pancreaticoduodenectomy (PPPD) or subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) with standard lymphadenectomy. In addition, classic Child reconstruction was performed with resection of the distal stomach. If peritoneal metastasis or major vascular invasion was identified during surgery, palliative treatment consisting of gastrojejunostomy was performed. Study outcomes, definitions and Statistical analyses The primary outcomes of this study were the rate of RBO and the time to RBO (TRBO) until surgery in the LBPS and SEMS groups. Secondary outcomes included the technical success rate, clinical success rate, ERCP- and stent-related AEs, and surgery-related outcomes in the two groups. Technical success was defined as successful biliary stent placement at the appropriate location. Clinical success was defined as a ≥ 50% reduction or normalization of total bilirubin or liver enzyme levels within 14 days. The definitions and severity grading of ERCP- or stent-related AEs were evaluated according to the 2024 Tokyo Criteria for Transpapillary Biliary Stenting ( 13 ). RBO was defined as stent occlusion, stent migration, or any condition requiring re-intervention, such as biliary drainage or stent removal. Stent migration was defined as stent dislocation confirmed by endoscopic findings or imaging studies. Stent occlusion included tumor overgrowth, tumor ingrowth, sludge formation, and food impaction. TRBO was defined as the time interval from stent placement to the occurrence of RBO. Non-RBO AEs, including pancreatitis, cholangitis, cholecystitis, bleeding, and perforation, were determined based on the 2024 TOKYO criteria. Non-RBO AEs were defined as events requiring conservative treatment, medication, intervention, or hospitalization. Surgery-related outcomes included the curative resection rate, operative time, intraoperative blood loss, and the incidence of postoperative AEs. Postoperative AEs were graded according to the Clavien-Dindo (CD) classification and the definitions of the International Study Group on Pancreatic Fistula; AEs greater than Grade III were considered significant ( 14 , 15 ). A clinically curative resection was defined as R0 surgery, in which no cancer cells were observed microscopically at the surgical margins. Continuous variables were reported as medians with ranges or interquartile ranges (IQRs). Categorial variables were compared using Fisher's exact test or Pearson's chi-squared test, as appropriate, and continuous variables were compared using the Mann-Whitney U test. TRBO were estimated using the Kaplan–Meier method, and cumulative incidence was compared between the LBPS and SEMS groups using the log-rank test. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for RBO, with 95% confidence interval (CIs). Factors associated with RBO (P < 0.20) in univariable analysis were further evaluated using multivariable analysis. Statistical significance was set at P < 0.05. All statistical analyses were performed using JMP version 18 (SAS Institute 2, Inc., Cary, NC, USA). Results Patient selection A total of 238 patients underwent preoperative drainage for obstructive jaundice caused by pancreatic cancer at the 4 centers during the study period. Among these patients, 14 were excluded for the following reasons: biliary drainage with PS smaller than 11.5-Fr in 144 patients, initial biliary drainage (PTBD or EUS-BD) in five patients, biliary drainage at other centers in four patients, AEs before stent deployment in three patients, and refusal of treatment due to old age in two patients. After screening, 80 patients fulfilled the eligibility criteria and were included in this study; for biliary drainage, LBPS was placed in 20 patients and SEMS in 60 patients. (Fig. 2 ). Baseline characteristics and endoscopic procedures Patient characteristics of the two groups are summarized in Table 1 . Significant differences between the two groups were identified with respect to the initial total albumin level, history of endoscopic sphincterotomy (EST), and biliary stricture length. The endoscopic procedures performed in the two groups are summarized in Table 2 . No significant differences were observed between the groups with respect to the cannulation method, pancreatography, pancreatic stent, and EST. There were more prophylactic rectal NSAIDs administered in the LBPS group. ERCP-related outcomes The ERCP-related outcomes of the two groups are summarized in Table 2 . The technical success rate was 100% in both groups. The clinical success rates were 95.0% (19/20) in the LBPS group and 93.3% (56/60) in the SEMS group, respectively ( P > 0.99). In the five cases of clinical failure (one in the LBPS exchange group and four in the SEMS group), all patients experienced early stent occlusion or migration within two weeks of placement, all patients underwent stent exchange. The overall incidence of AE related to ERCP and stent placement was 30.0% in the LBPS group and 43.3% in the SEMS group, respectively (P = 0.429). RBO occurred in 20.0% and 25.0% of the patients in the LBPS and SEMS groups, respectively (P = 0.768). Other than RBO, pancreatitis, cholecystitis and non-obstructive cholangitis were observed in 0% vs. 18.3% (P = 0.057), 0% vs. 8.3% (P = 0.323), and 10.5% vs. 3.3% (P = 0.258), respectively. In the SMES group, there were nine mild cases and two moderate cases of pancreatitis, which improved with conservative treatment without developing local complications such as walled-off necrosis. Of the five cases of cholecystitis, two were successfully managed with conservative treatment, but three required percutaneous transhepatic gallbladder drainage (PTGBD). Two cases of non-obstructive cholangitis in the LBPS group and two cases in the SEMS group were successfully treated with antibiotics. The median time to surgery was 64 days (IQR, 45–78 days) in the LBPS group and 73 days (IQR, 29–106 days) in the SEMS group, with no significant differences (P = 0.426). In the Kaplan-Meier analysis, there was no significant difference in the time to RBO (TRBO) between the two groups (hazard ratio for RBO, 0.567; 95% CI, 0.186–1.727; log-rank P = 0.310; Fig. 3 ). In univariable and multivariable analyses, only a dilated bile duct was identified as a risk factor for RBO; however, LBPS itself was not a risk factor for RBO (Table 3 ). Surgery-related outcomes The surgery-related outcomes of the two groups are summarized in Table 4 . Surgical resection was successful in 60.0% in the LBPS group and 80.0% in the SEMS group, respectively (P = 0.133). Regarding surgical procedures, SSPPD were significantly more common in the LBPS group; however, the curative surgery rates were 91.6% and 72.9% in the LBPS and SEMS groups, respectively, with no significant differences. The median surgery times were 409 and 542 min in the LBPS and SEMS groups, respectively, and were significantly shorter in the LBPS group (P < 0.001). Surgery-related AE occurred in 16.6% (2/12: pancreatic fistula in two patients) of the LBPS group and 14.5% (7/48: pancreatic fistula in one patient, biloma in three patients, abscess in one patient, and others in four patients) of the SEMS group (P > 0.99). The median time of post-operative hospital stay in the LBPS and SEMS groups was 21 and 27 days, respectively, and tended to be shorter in the LBPS group (P = 0.080). Discussion Summary of the results of this study This study compared the clinical outcomes of LBPS and SEMS placement for the preoperative management of biliary obstruction in patients with resectable pancreatic cancer. RBO occurred in 20.0% and 25.0% of the patients in the LBPS and SEMS groups, respectively, which was not significantly different. TRBO was similar in both groups, and in a multivariable analysis examining factors affecting RBO, the type of stent itself was not identified as a significant factor. In contrast, the incidence rates of pancreatitis and cholecystitis were tended to be higher in the SEMS group. Regarding surgery-related outcomes, no significant differences were observed between the two groups in curative surgery rate, intraoperative bleeding volume, and AEs, but the surgical time was significantly shorter in the LBPS group, and the length of hospital stay also tended to be shorter in the LBPS group. Usefulness and issues of SEMS in preoperative biliary drainage for pancreatic cancer In recent years, NAC has become the mainstream preoperative treatment for pancreatic cancer, and the waiting period before surgery has been extended ( 1 – 5 ). Before the introduction of NAC, the waiting period for surgery was between 12–36 days; however, it has been reported that this extended to 72–165 days after the introduction of NAC ( 16 ). PS has traditionally been used as a biliary stent for preoperative drainage in patients with pancreatic cancer, however, SEMS are now recommended considering the extended preoperative period. Kobayashi et al. retrospectively compared the SEMS group (n = 21) and PS group (n = 22) for preoperative biliary drainage caused by pancreatic cancer ( 17 ). In the SEMS group, 8-mm fully covered metallic stents were used, whereas in the PS group, 7-Fr plastic stents were used. During the waiting period for surgery, RBO occurred in 4.8% and 95.4% of patients in the SEMS and PS groups, respectively (p < 0.001). The TRBO was significantly longer in the SEMS group than in the PS group. These results suggest that SEMS have a significantly longer patency than PS and are useful as biliary drainage stents for preoperative pancreatic cancer. However, a disadvantage of SEMS is the high incidence of AEs other than RBO, such as pancreatitis and cholecystitis ( 18 – 21 ). A retrospective study by Ichikawa et al. compared SEMS (n = 45) and PS (n = 75) groups for preoperative biliary drainage in patients with pancreatic cancer ( 18 ). The RBO rate was significantly lower in the SEMS group (24.4% vs. 44.0%, P = 0.034), and the TRBO was significantly longer in the SEMS group. However, pancreatitis and cholecystitis were observed in 15.6% and 2.7% (P = 0.026) and 6.7% and 0% (P = 0.051) in the SEMS and PS groups, respectively. Cote et al. conducted a retrospective study to investigate the risk factors of post-ERCP pancreatitis (PEP) ( 20 ). They enrolled 544 patients who underwent stent placement for malignant biliary obstruction, with 248 and 296 patients in the SEMS and PS groups, respectively. The frequency of PEP was significantly higher in the SEMS group (7.3%) than in the PS group (1.3%) (P < 0.01). The results showed that the frequency of post-ERCP pancreatitis was significantly higher in the SEMS group. Cao et al. retrospectively examined the risk factors of post-ERCP cholecystitis in 4238 patients who underwent their first ERCP ( 21 ). Univariate and multivariate analyses identified biliary duct SEMS placement as a risk factor for post-ERCP cholecystitis (OR, 3.66; 95% CI 1.78–7.54). In the current study, pancreatitis and cholecystitis were observed in 0% vs. 18.3% and 0% vs. 8.3% of the patients in the LBPS and SEMS groups, respectively, and tended to be higher in the SEMS group. These results suggest that SEMS for preoperative biliary drainage of pancreatic cancer has a significantly higher incidence of AEs, such as pancreatitis and cholecystitis, than PS, and there is concern that these AEs may lead to the postponement of NAC or surgery itself. In other words, the relationship between stent patency based on caliber and AEs other than RBO (pancreatitis and cholecystitis) is thought to be a trade-off. In preoperative drainage for pancreatic cancer, a stent strategy that takes into consideration not only RBO but also AEs such as pancreatitis and cholecystitis is required. Outcomes of preoperative biliary drainage using large-bore PS for pancreatic cancer and its impact on surgery The PS used for preoperative biliary drainage of pancreatic cancer has insufficient patency, and to compensate for this weakness, it is necessary to increase its caliber. Traditionally, a 7-Fr PS has been used primarily for the preoperative drainage of pancreatic cancer, but there have been several reports examining the results of upgrading to a 10-Fr PS. Mandai et al. conducted a multicenter randomized controlled trial (RCT) to compare the clinical outcomes of 10-mm SEMS (n = 17) and 10-Fr PS (n = 22) for preoperative biliary drainage in pancreatic cancer ( 19 ). The re-intervention rates were 0% in the SEMS group and 29.4% in the PS group, and patency was significantly longer in the SEMS group than in the PS group. Another RCT by Tamura et al. evaluated a 10-mm SEMS (n = 11) and 10-Fr PS (n = 11) for preoperative biliary drainage in ancreatic cancer ( 22 ). The SEMS group showed a significantly lower rate of RBO (18.2% vs. 72.8%, P = 0.015), longer stent patency, and fewer reinterventions for stent dysfunction than the PS group. These results suggest that the caliber of a 10-Fr PS is insufficient for preoperative biliary drainage in patients with pancreatic cancer, and that its patency is significantly shorter than that of the SEMS. However, it should be noted that all these reports had relatively small sample sizes. The LBPS used in this study is a new type of plastic stent with a larger diameter of 11.5 Fr. The LBPS has three drainage lumens, and the side holes are larger than those of the conventional PS; therefore, excellent drainage effects can be expected. In the current study, the incidence of RBO during the waiting period for surgery in the LBPS group was comparable to that in the SEMS group, and no significant difference in TRBO was observed between the two groups. Furthermore, the incidence of AEs other than RBO, such as pancreatitis and cholecystitis, was 0% in the LBPS group, whereas the SEMS group had higher rates at 18.3% and 8.3%, respectively. These results suggest that LBPS has the same patency as SEMS and reduces the occurrence of AEs other than RBO. However, there is currently insufficient evidence regarding the effects of PS and SEMS use on surgery. Tamura et al. conducted an RCT to compare the effects of SEMS (n = 7) and PS (n = 9) placement in pancreatic cancer surgery and found no significant differences between the two groups in terms of operation time, intraoperative blood loss, postoperative hospitalization, or postoperative AEs ( 22 ). Another RCT by Mandai et al., which compared a SEMS group (n = 17) with a PS group (n = 22), revealed that the SEMS group had significantly more intraoperative blood loss and AE than the PS group, and the postoperative hospital stay was significantly longer in the SEMS group ( 19 ). In the current study, no significant differences were observed between the two groups in curative surgery rate, intraoperative bleeding volume, and AEs, but the surgical time was significantly shorter in the LBPS group, and the length of hospital stay also tended to be shorter in the LBPS group. These results suggest that PS, including LBPS, is unlikely to have a negative effect on surgery and may actually have less of an effect than SEMS. 6-mm SEMS for preoperative biliary drainage of pancreatic cancer In recent years, the 6-mm SEMS has attracted attention as a preoperative drainage for pancreatic cancer, considering the trade-off between patency and AEs depending on the stent diameter. Kataoka et al. conducted a retrospective comparative study of the clinical outcomes of a 6-mm SEMS group (n = 26) and a PS group (n = 25) for preoperative biliary drainage for pancreatic cancer ( 23 ). The incidence of RBO was significantly lower in the 6-mm SEMS group (7.7%) than that in the PS group (40.0%), and TRBO was significantly longer in the 6-mm SEMS group. The groups did not significantly differ in terms of AEs other than RBO, such as pancreatitis (15.4% vs. 4.0%) and cholecystitis (7.7% vs. 4.0%). Sakai et al. conducted a retrospective comparative study on the outcomes of 6-mm (n = 27) and 10-mm SEMS (n = 26) in preoperative biliary drainage for pancreatic cancer ( 24 ). The RBO rate was 26.9% in the 6-mm SEMS group, which was significantly higher than that in the 10-mm SEMS group (7.7%), and the rate of migration was particularly high at 26.9%. Although there was no significant difference between the two groups in terms of non-RBO AEs, the incidence of pancreatitis was 3.7% vs. 11.5%, and the incidence of cholecystitis was 0% vs. 7.7%, both of which were higher in the 10-mm SEMS group. These results suggest that a 6-mm SEMS can maintain longer patency than a PS and that it can also reduce the occurrence of non-RBO complications such as pancreatitis and cholecystitis compared to a 10-mm SEMS. However, this also suggests that the 6-mm SEMS has a higher RBO owing to migration. In the current study, the 11.5-Fr LBPS demonstrated its usefulness and safety as a stent with patency equivalent to that of a SEMS and suppressed non-RBO AEs such as pancreatitis and cholecystitis; however, there have been no previous reports comparing it with a 6-mm SEMS. In many cases of suspected malignant biliary obstruction due to pancreatic cancer, a PS is often initially placed, if it is replaced with a SEMS after the diagnosis is confirmed, an additional ERCP session is required. However, if an LBPS is placed as the initial stent, additional ERCP is not required to exchange the stent after the diagnosis is confirmed, and NAC treatment can be initiated early. Thus, it is considered that there is great significance in selecting LBPS as the initial stent for preoperative biliary drainage in pancreatic cancer patients. Based on the results of this study, an 11.5-Fr LBPS may be the first choice for preoperative biliary drainage for pancreatic cancer. However, considering that current guidelines recommend SEMS, one option is to actively use it in cases at high risk of post-ERCP pancreatitis or cholecystitis. The American Society for Gastrointestinal Endoscopy (ASGE) and European Society of Gastrointestinal Endoscopy ( ESGE) guidelines state that factors that increase the risk of pancreatitis include young age, female gender, and a history of acute pancreatitis or PEP ( 25 , 26 ). In addition, the risk of developing cholecystitis due to SEMS placement has been reported to include tumor involvement in the orifice of the cystic duct and intragallbladder stones ( 27 – 30 ). In these cases, 11.5-Fr LBPS is considered a good option to avoid the development of pancreatitis and cholecystitis due to SEMS placement. This study demonstrated the usefulness and safety of LBPS. However, there is currently no established strategy for determining the optimal stent type and diameter for preoperative biliary drainage of pancreatic cancer, and further investigation in larger prospective comparative studies is needed. Limitation This study has several limitations. First, the sample size is small. Second, it was retrospective and conducted at four tertiary care centers, which could potentially have introduced selection bias and reduced its external validity. Third, LBPS was used more frequently during the later phases of the study period. This could have introduced bias in the endoscopic and surgical outcomes, as diagnostic and therapeutic modalities evolved during the study. Fourth, the impact of LBPS and SEMS placement on surgery may not have been fully evaluated using the current items alone. Conclusion In conclusion, 11.5-Fr LBPS had a patency equivalent to that of SEMS and a low incidence of non-RBO AEs, such as pancreatitis and cholecystitis; therefore, it may become the first choice for preoperative biliary drainage in pancreatic cancer. A prospective randomized controlled trial with a larger cohort is required to validate these findings. Abbreviations AE, adverse event; ERCP, endoscopic retrograde cholangiopancreatography; EST, endoscopic sphincterotomy; EUS-BD, endoscopic ultrasound-guided biliary drainage EUS-FNA, endoscopic ultrasound-guided fine needle aspiration; EUS-FNB, endoscopic ultrasound-guided fine needle biopsy; HR, hazard ratio; IQR, interquartile range; LBPS, large bore plastic stent NAC, neoadjuvant chemotherapy; PEP, post-ERCP pancreatitis; PTBD, percutaneous transhepatic biliary drainage RBO, recurrent biliary obstruction; SEMS, self-expandable metallic stent; TRBO, time to recurrent biliary obstruction; UICC, Union for International Cancer Control; 95% CI, 95% confidence interval. Declarations Author Contributions: Akinori Maruta wrote the manuscript. Akinori Maruta, Takuya Koizumi, Kota Shimojo, Yosuke Ohashi, Shota Iwata, Hironao Ichikawa, Naoki Mita, Yuhei Iwasa, Mitsuru Okuno, Shinya Uemura, Keisuke Iwata, Tsuyoshi Mukai, Takuji Iwashita, Masahito Shimizu managed the patients. Akinori Maruta took the correspondence. All authors read and approved the final manuscript. Conflicts of Interest: Authors declare no conflicts of interest for this article. References Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, et al. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J Clin Oncol. 2020;38(16):1763–73. Murakami Y, Uemura K, Sudo T, Hashimoto Y, Kondo N, Nakagawa N, et al. Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients with borderline resectable pancreatic carcinoma with arterial contact. Cancer Chemother Pharmacol. 2017;79(1):37–47. Fujii T, Satoi S, Yamada S, Murotani K, Yanagimoto H, Takami H, et al. Clinical benefits of neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreatic head: an observational study using inverse probability of treatment weighting. J Gastroenterol. 2017;52(1):81–93. Motoi F, Kosuge T, Ueno H, Yamaue H, Satoi S, Sho M, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol. 2019;49(2):190–4. Versteijne E, van Dam JL, Suker M, Janssen QP, Groothuis K, Akkermans-Vogelaar JM, et al. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. 2022;40(11):1220–30. Dumonceau JM, Tringali A, Papanikolaou IS, Blero D, Mangiavillano B, Schmidt A, et al. Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline - Updated October 2017. Endoscopy. 2018;50(9):910–30. Takeda T, Sasaki T, Mie T, Furukawa T, Kanata R, Kasuga A, et al. Novel risk factors for recurrent biliary obstruction and pancreatitis after metallic stent placement in pancreatic cancer. Endosc Int Open. 2020;8(11):E1603-E10. Kumar N, Jena A, Sharma V, Shukla S, Shah J. Outcome of metal vs plastic stents for biliary obstruction in patients with pancreatic carcinoma undergoing neoadjuvant chemoradiotherapy: A systematic review and meta-analysis. J Hepatobiliary Pancreat Sci. 2023;30(4):419–28. Ishiwatari H, Kobayashi Y, Kawaguchi S, Iwashita T, Kaneko J, Ito J, et al. Assessment of safety and patency of 7-mm covered metal stents for preoperative biliary drainage in pancreatic cancer: Prospective multicenter study. Endosc Int Open. 2025;13:a25031995. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9. Yamada S, Fujii T, Takami H, Hayashi M, Iwata N, Kanda M, et al. Evaluation and proposal of novel resectability criteria for pancreatic cancer established by the Japan Pancreas Society. Surgery. 2017;162(4):784–91. Okusaka T, Nakamura M, Yoshida M, Kitano M, Ito Y, Mizuno N, et al. Clinical Practice Guidelines for Pancreatic Cancer 2022 from the Japan Pancreas Society: a synopsis. Int J Clin Oncol. 2023;28(4):493–511. Isayama H, Hamada T, Fujisawa T, Fukasawa M, Hara K, Irisawa A, et al. TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage. Dig Endosc. 2024;36(11):1195–210. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. Bassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138(1):8–13. Hasegawa S, Endo I, Kubota K. Plastic or self-expandable metal stent: Which is the most suitable for patients with pancreatic head cancer in the upcoming era of neoadjuvant chemotherapy? A review. Dig Endosc. 2022;34(2):297–306. Kobayashi K, Kobara H, Kamada H, Kohno T, Namima D, Fujita N, et al. Comparison of plastic stent versus metal stent in preoperative biliary drainage for pancreatic head cancer with neoadjuvant chemoradiotherapy. J Hepatobiliary Pancreat Sci. 2021;28(10):856–63. Ichikawa H, Iwashita T, Iwasa Y, Uemura S, Tezuka R, Okuno M, et al. Covered self-expandable metallic stent versus plastic stent for preoperative endoscopic biliary drainage in patients with pancreatic cancer: a multi-center retrospective cohort study. Scand J Gastroenterol. 2022;57(4):493–500. Mandai K, Tsuchiya T, Kawakami H, Ryozawa S, Saitou M, Iwai T, et al. Fully covered metal stents vs plastic stents for preoperative biliary drainage in patients with resectable pancreatic cancer without neoadjuvant chemotherapy: A multicenter, prospective, randomized controlled trial. J Hepatobiliary Pancreat Sci. 2022;29(11):1185–94. Cote GA, Kumar N, Ansstas M, Edmundowicz SA, Jonnalagadda S, Mullady DK, et al. Risk of post-ERCP pancreatitis with placement of self-expandable metallic stents. Gastrointest Endosc. 2010;72(4):748–54. Cao J, Peng C, Ding X, Shen Y, Wu H, Zheng R, et al. Risk factors for post-ERCP cholecystitis: a single-center retrospective study. BMC Gastroenterol. 2018;18(1):128. Tamura T, Itonaga M, Ashida R, Yamashita Y, Hatamaru K, Kawaji Y, et al. Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study. Dig Endosc. 2021;33(7):1170–8. Kataoka F, Inoue D, Watanabe M, Fukuda K, Nobusawa T, Umemura K, et al. Efficacy of 6-mm diameter fully covered self-expandable metallic stents in preoperative biliary drainage for pancreatic ductal adenocarcinoma. DEN Open. 2022;2(1):e55. Sakai A, Masuda A, Takenaka M, Shiomi H, Omoto S, Yoshida A, et al. Multicenter Comparative Study of 6- and 10-mm Fully Covered Self-Expandable Metal Stents for Malignant Distal Biliary Obstruction During Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Cancer. J Hepatobiliary Pancreat Sci. 2025;32(7):554–61. Kang H, Park CH, Ryu K. Prevention, Detection, and Management of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis. Gut Liver. 2025;19(6):795–808. Dumonceau JM, Kapral C, Aabakken L, Papanikolaou IS, Tringali A, Vanbiervliet G, et al. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2020;52(2):127–49. Shimizu S, Naitoh I, Nakazawa T, Hayashi K, Miyabe K, Kondo H, et al. Predictive factors for pancreatitis and cholecystitis in endoscopic covered metal stenting for distal malignant biliary obstruction. J Gastroenterol Hepatol. 2013;28(1):68–72. Nakai Y, Isayama H, Kawakubo K, Kogure H, Hamada T, Togawa O, et al. Metallic stent with high axial force as a risk factor for cholecystitis in distal malignant biliary obstruction. J Gastroenterol Hepatol. 2014;29(7):1557–62. Takinami M, Murohisa G, Yoshizawa Y, Shimizu E, Nagasawa M. Risk factors for cholecystitis after stent placement in patients with distal malignant biliary obstruction. J Hepatobiliary Pancreat Sci. 2020;27(8):470–6. Albunni H, Beran A, Hadaki N, Gromski MA, Al-Haddad M. Risk Factors for Cholecystitis After Self-expandable Metallic Stent Placement for Malignant Distal Biliary Obstruction: A Systematic Review and Meta-analysis. J Clin Gastroenterol. 2025. Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Table2.docx Table3.docx Table4.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 09 May, 2026 Reviewers agreed at journal 08 May, 2026 Reviewers invited by journal 19 Apr, 2026 Editor assigned by journal 15 Apr, 2026 Submission checks completed at journal 15 Apr, 2026 First submitted to journal 10 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9383752","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":627193217,"identity":"ab23dd1e-b773-4d3c-90df-111a35613396","order_by":0,"name":"Akinori Maruta","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYHACZuYfFWzM/AwMbDCRBMJaGM7wsUs2kKSFsU2O3+AAQgt+oDv78GPjgjNm0sY3kp89+FDBIA904bMH+LSYnUszTp5RkWZsdiPN3HDGGQbDmQ0M6QZ4tZxhMD7Ac+ZYstmNBDNp3jaGBKAL0yTwa2H/fIC37X/95hnp34jVwmOczNvGxmwgkUO0LTzFQC+wMUuceVMmOeOMhOHMZoJ+Yd8s8QEUle3p24AMG3l+9p60B/i0IIBAAogEOomZJ404HQz8B2As9mNEahkFo2AUjIIRAgBjYETy7Us5pwAAAABJRU5ErkJggg==","orcid":"","institution":"Gifu University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Akinori","middleName":"","lastName":"Maruta","suffix":""},{"id":627193218,"identity":"6b99c988-b632-482a-8034-239afcc770f0","order_by":1,"name":"Takuya Koizumi","email":"","orcid":"","institution":"Gifu University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Takuya","middleName":"","lastName":"Koizumi","suffix":""},{"id":627193219,"identity":"e32a1246-fcc6-47f2-990e-14f91e003295","order_by":2,"name":"Kota 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Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tsuyoshi","middleName":"","lastName":"Mukai","suffix":""},{"id":627193229,"identity":"d8272a89-5434-4f18-a99c-3889d0c8869d","order_by":12,"name":"Takuji Iwashita","email":"","orcid":"","institution":"Shiga University of Medical Science","correspondingAuthor":false,"prefix":"","firstName":"Takuji","middleName":"","lastName":"Iwashita","suffix":""},{"id":627193230,"identity":"1a995005-ae43-4bbb-91f6-2b6ef7700d2a","order_by":13,"name":"Masahito Shimizu","email":"","orcid":"","institution":"Gifu University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masahito","middleName":"","lastName":"Shimizu","suffix":""}],"badges":[],"createdAt":"2026-04-11 01:53:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9383752/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9383752/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108009962,"identity":"5cec7912-df70-48e9-9cf5-db2c52881738","added_by":"auto","created_at":"2026-04-28 13:12:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56936,"visible":true,"origin":"","legend":"\u003cp\u003ea, b. 11.5-Fr LBPS (Oasis® One Action Stent Introduction System Preloaded with Cotton-Leung® Biliary Stent, Cook Medical Japan G.K.). There are three drainage lumens at the tip of the stent (red arrows).\u003c/p\u003e\n\u003cp\u003eLBPS; large-bore plastic stent.\u003c/p\u003e","description":"","filename":"1ab.png","url":"https://assets-eu.researchsquare.com/files/rs-9383752/v1/afe56cd6988f0dae31028496.png"},{"id":108011494,"identity":"e018e3b3-9b21-44d4-9df5-8528a52acf89","added_by":"auto","created_at":"2026-04-28 13:14:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50894,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the patient selection process.\u003c/p\u003e\n\u003cp\u003eAEs, adverse events; BSC, best supportive care; EUS-BD, endoscopic ultrasound-guided biliary drainage; LBPS, large-bore plastic stent; PTBD, percutaneous transhepatic biliary drainage; SEMS, self-expandable metallic stent.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-9383752/v1/2156d55db1bedc49879f68bd.png"},{"id":108010333,"identity":"cbe77412-3436-422d-8fec-9dbc5cf4fd1a","added_by":"auto","created_at":"2026-04-28 13:13:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":34789,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier analysis of the incidence rate of RBO.\u003c/p\u003e\n\u003cp\u003eLBPS, large-bore plastic stent; RBO, recurrent biliary obstruction; SEMS, self-expandable metallic stent; 95% CI, 95% confidence interval.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-9383752/v1/0d11f2ead19bcd0d7e0d6870.png"},{"id":108012888,"identity":"2a804679-c947-4cda-a219-22e8b0904a73","added_by":"auto","created_at":"2026-04-28 13:16:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":336785,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9383752/v1/be7ad6fc-14fd-4b12-8deb-9b1fe322e8cb.pdf"},{"id":108009858,"identity":"449d589d-e0d2-4a58-b060-3ffca3a4d4b2","added_by":"auto","created_at":"2026-04-28 13:11:40","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":24393,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-9383752/v1/87f647067b4cbb9bc712258d.docx"},{"id":108009965,"identity":"e3f007fa-0226-49a1-bda6-8b672c378e6e","added_by":"auto","created_at":"2026-04-28 13:12:03","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24750,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.docx","url":"https://assets-eu.researchsquare.com/files/rs-9383752/v1/f46867ce929d5e1e6f77bdb9.docx"},{"id":108009961,"identity":"3db76bce-0925-4e98-aac0-4a77f1a72e38","added_by":"auto","created_at":"2026-04-28 13:12:02","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":24497,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.docx","url":"https://assets-eu.researchsquare.com/files/rs-9383752/v1/6c6661e21ed69af18fed024f.docx"},{"id":108009860,"identity":"e5895c74-b1ef-4d00-b856-b56e9be341f1","added_by":"auto","created_at":"2026-04-28 13:11:42","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":24338,"visible":true,"origin":"","legend":"","description":"","filename":"Table4.docx","url":"https://assets-eu.researchsquare.com/files/rs-9383752/v1/68a36aa01d081546f3b8e20d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"11.5-Fr Large bore plastic stents versus fully covered self-expandable metallic stents for the management of preoperative endoscopic biliary obstruction in pancreatic cancer: a multicenter retrospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePancreatic cancer often causes obstructive jaundice, for which endoscopic biliary drainage using endoscopic retrograde cholangiopancreatography (ERCP) is the treatment of choice. Plastic stents (PS) have traditionally been used for preoperative biliary drainage in patients with pancreatic cancer. The advantages of PS include their relative ease of placement, ability to be replaced and removed, and low cost. In recent years, however, preoperative neoadjuvant chemotherapy (NAC) has become the standard treatment, resulting in a longer preoperative waiting period compared with conventional upfront surgery (\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Given this extended waiting period associated with NAC, the patency of PS is often insufficient, and the European Society of Gastrointestinal Endoscopy (ESGE) guidelines therefore recommend a 10-mm self-expandable metallic stent (SEMS) for preoperative drainage (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Although SEMS have a large caliber and are expected to prolong patency, they have been reported to be associated with a high incidence of non-recurrent biliary obstruction (RBO)-related adverse events (AEs), such as pancreatitis and cholecystitis (\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). These AEs raise concerns regarding potential discontinuation of NAC or postponement of surgery. Furthermore, evidence regarding the effects of SEMS on surgical outcomes remains limited. In contrast, the 11.5-Fr large-bore plastic stent (LBPS) (Oasis\u0026reg; One Action Stent Introduction System Preloaded with Cotton-Leung\u0026reg; Biliary Stent, Cook Medical Japan G.K.) is a newly developed stent with a larger diameter than conventional PS and three drainage lumens at the tip. Notably, the side holes are larger than those of conventional stents, suggesting improved drainage efficacy (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea.\u003cb\u003eb\u003c/b\u003e). The purpose of this study was to compare the clinical outcomes of LBPS and SEMS in preoperative biliary drainage for pancreatic cancer.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u0026rsquo; selection\u003c/h2\u003e \u003cp\u003e This retrospective cohort study was conducted at four tertiary care centers: Gifu University Hospital, Gifu Prefectural General Medical Center, Gifu Municipal Hospital, and Matsunami General Hospital. A database, which encompassing all patients who were histologically diagnosed with pancreatic cancer between January 2011 and December 2025, was analyzed to identify those who met the following inclusion criteria: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) pathologically comfirmed pancreatic cancer classified as resectable or borderline resectable based on computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasound-guided fine needle aspiration or biopsy (EUS-FNA/FNB); (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) underwent preoperative biliary drainage for obstructive jaundice due to pancreatic cancer using either LBPS or 8-12mm fully covered self-expandable metallic stent (FCSEMS); and (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) age older than 20 years. Patients were excluded if they met any of the following exclusion criteria: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) biliary drainage with PS smaller than 11.5-Fr LBPS, (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) biliary drainage performed using percutaneous transhepatic biliary drainage (PTBD) or endoscopic ultrasound-guided biliary drainage (EUS-BD), except for the rendezvous technique; (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) coexisting malignant biliary obstruction involving the hilar part of the biliary system, defined as within 2 cm below the biliary confluence; (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) biliary drainage performed at other institutions; (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) a prior history of surgical biliary reconstruction; or (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) adverse events (AEs), such as hemorrhage or perforation, occurring before stent deployment. Patients deemed ineligible for the study by the principal investigator and those who declined participation based on publicly available information were also excluded. Pancreatic cancer staging was performed according to the Union for International Cancer Control \u003cb\u003e(\u003c/b\u003eUICC) criteria (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Resectability was determined based on the clinical practice guidelines for pancreatic cancer issued by the Japan Pancreas Society (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Patients were divided into the LBPS and SEMS groups according to the type of stent used. Written informed consent was obtained from all patients prior to the procedures, and consent for the use of research data was obtained on an opt-out basis. All procedures in this study were conducted in accordance with the ethical standards of the institutional and national research committees and the principles of the 1964 Helsinki Declaration and its later amendments. The study protocol was approved by the Institutional Review Board of each participating institution (Gifu University Hospital: 2025\u0026thinsp;\u0026minus;\u0026thinsp;359) and was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN: 60443).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEndoscopic Procedures\u003c/h3\u003e\n\u003cp\u003eAll ERCP procedure were performed using a standard duodenoscope (TJF-260V, JF-260V, or JF-240; Olympus, Tokyo, Japan) under conscious sedation with midazolam and pentazocine, with continuous monitoring of vital signs. Bile duct cannulation was performed using a wire-loaded cannulation technique. If biliary cannulation was difficult with the standard approach, the pancreatic guidewire technique or pre-cutting was applied as needed. After successful selective bile duct cannulation, cholangiography was performed to evaluate the location and length of the malignant biliary obstruction. Endoscopic sphincterotomy (EST) or two-step drainage using endoscopic nasobiliary drainage (ENBD) was performed at the operator\u0026rsquo;s discretion. EST was performed using a papillotome (KD-211Q-0725 or KD-V411M-0725; Olympus, Tokyo, Japan, or Correctome; Boston Scientific, Massachusetts, USA) over a guidewire. A stent of sufficient length to cover both the obstruction and the duodenal papilla was selected for biliary drainage. Subsequently, a FCSEMS (8\u0026ndash;12 mm in diameter and 5\u0026ndash;8 cm in length) or LBPS (11.5-Fr and 5\u0026ndash;8 cm in length) was deployed at the obstruction site. The diameter, length, and type of stent were chosen at the discretion of each endoscopist. Antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and protease inhibitors were administered before or after ERCP according to institutional protocols.\u003c/p\u003e\n\u003ch3\u003eNeoadjuvant Chemotherapy\u003c/h3\u003e\n\u003cp\u003eAfter proper biliary drainage and improvement of liver function, NAC was performed in some patients. The regimens used were S-1, gemcitabine plus S-1, gemcitabine plus nab-paclitaxel, or FOLFIRINOX according to the discretion of each hospital. Contrast-enhanced CT or MRI is generally performed for restaging after the completion of NAC. The final decision to perform surgical exploration was made by an expert panel of endoscopists, surgeons, and radiologists.\u003c/p\u003e\n\u003ch3\u003eSurgical resection\u003c/h3\u003e\n\u003cp\u003eThe standard surgical procedures included pylorus-preserving pancreaticoduodenectomy (PPPD) or subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) with standard lymphadenectomy. In addition, classic Child reconstruction was performed with resection of the distal stomach. If peritoneal metastasis or major vascular invasion was identified during surgery, palliative treatment consisting of gastrojejunostomy was performed.\u003c/p\u003e\n\u003ch3\u003eStudy outcomes, definitions and Statistical analyses\u003c/h3\u003e\n\u003cp\u003eThe primary outcomes of this study were the rate of RBO and the time to RBO (TRBO) until surgery in the LBPS and SEMS groups. Secondary outcomes included the technical success rate, clinical success rate, ERCP- and stent-related AEs, and surgery-related outcomes in the two groups. Technical success was defined as successful biliary stent placement at the appropriate location. Clinical success was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;50% reduction or normalization of total bilirubin or liver enzyme levels within 14 days. The definitions and severity grading of ERCP- or stent-related AEs were evaluated according to the 2024 Tokyo Criteria for Transpapillary Biliary Stenting (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). RBO was defined as stent occlusion, stent migration, or any condition requiring re-intervention, such as biliary drainage or stent removal. Stent migration was defined as stent dislocation confirmed by endoscopic findings or imaging studies. Stent occlusion included tumor overgrowth, tumor ingrowth, sludge formation, and food impaction. TRBO was defined as the time interval from stent placement to the occurrence of RBO. Non-RBO AEs, including pancreatitis, cholangitis, cholecystitis, bleeding, and perforation, were determined based on the 2024 TOKYO criteria. Non-RBO AEs were defined as events requiring conservative treatment, medication, intervention, or hospitalization.\u003c/p\u003e \u003cp\u003eSurgery-related outcomes included the curative resection rate, operative time, intraoperative blood loss, and the incidence of postoperative AEs. Postoperative AEs were graded according to the Clavien-Dindo (CD) classification and the definitions of the International Study Group on Pancreatic Fistula; AEs greater than Grade III were considered significant (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). A clinically curative resection was defined as R0 surgery, in which no cancer cells were observed microscopically at the surgical margins.\u003c/p\u003e \u003cp\u003eContinuous variables were reported as medians with ranges or interquartile ranges (IQRs). Categorial variables were compared using Fisher's exact test or Pearson's chi-squared test, as appropriate, and continuous variables were compared using the Mann-Whitney U test. TRBO were estimated using the Kaplan\u0026ndash;Meier method, and cumulative incidence was compared between the LBPS and SEMS groups using the log-rank test. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for RBO, with 95% confidence interval (CIs). Factors associated with RBO (P\u0026thinsp;\u0026lt;\u0026thinsp;0.20) in univariable analysis were further evaluated using multivariable analysis. Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. All statistical analyses were performed using JMP version 18 (SAS Institute 2, Inc., Cary, NC, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient selection\u003c/h2\u003e\n \u003cp\u003eA total of 238 patients underwent preoperative drainage for obstructive jaundice caused by pancreatic cancer at the 4 centers during the study period. Among these patients, 14 were excluded for the following reasons: biliary drainage with PS smaller than 11.5-Fr in 144 patients, initial biliary drainage (PTBD or EUS-BD) in five patients, biliary drainage at other centers in four patients, AEs before stent deployment in three patients, and refusal of treatment due to old age in two patients. After screening, 80 patients fulfilled the eligibility criteria and were included in this study; for biliary drainage, LBPS was placed in 20 patients and SEMS in 60 patients. (Fig. \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eBaseline characteristics and endoscopic procedures\u003c/h3\u003e\n\u003cp\u003ePatient characteristics of the two groups are summarized in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Significant differences between the two groups were identified with respect to the initial total albumin level, history of endoscopic sphincterotomy (EST), and biliary stricture length. The endoscopic procedures performed in the two groups are summarized in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. No significant differences were observed between the groups with respect to the cannulation method, pancreatography, pancreatic stent, and EST. There were more prophylactic rectal NSAIDs administered in the LBPS group.\u003c/p\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eERCP-related outcomes\u003c/h2\u003e\n \u003cp\u003eThe ERCP-related outcomes of the two groups are summarized in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The technical success rate was 100% in both groups. The clinical success rates were 95.0% (19/20) in the LBPS group and 93.3% (56/60) in the SEMS group, respectively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.99). In the five cases of clinical failure (one in the LBPS exchange group and four in the SEMS group), all patients experienced early stent occlusion or migration within two weeks of placement, all patients underwent stent exchange. The overall incidence of AE related to ERCP and stent placement was 30.0% in the LBPS group and 43.3% in the SEMS group, respectively (P\u0026thinsp;=\u0026thinsp;0.429). RBO occurred in 20.0% and 25.0% of the patients in the LBPS and SEMS groups, respectively (P\u0026thinsp;=\u0026thinsp;0.768). Other than RBO, pancreatitis, cholecystitis and non-obstructive cholangitis were observed in 0% vs. 18.3% (P\u0026thinsp;=\u0026thinsp;0.057), 0% vs. 8.3% (P\u0026thinsp;=\u0026thinsp;0.323), and 10.5% vs. 3.3% (P\u0026thinsp;=\u0026thinsp;0.258), respectively. In the SMES group, there were nine mild cases and two moderate cases of pancreatitis, which improved with conservative treatment without developing local complications such as walled-off necrosis. Of the five cases of cholecystitis, two were successfully managed with conservative treatment, but three required percutaneous transhepatic gallbladder drainage (PTGBD). Two cases of non-obstructive cholangitis in the LBPS group and two cases in the SEMS group were successfully treated with antibiotics. The median time to surgery was 64 days (IQR, 45\u0026ndash;78 days) in the LBPS group and 73 days (IQR, 29\u0026ndash;106 days) in the SEMS group, with no significant differences (P\u0026thinsp;=\u0026thinsp;0.426). In the Kaplan-Meier analysis, there was no significant difference in the time to RBO (TRBO) between the two groups (hazard ratio for RBO, 0.567; 95% CI, 0.186\u0026ndash;1.727; log-rank P\u0026thinsp;=\u0026thinsp;0.310; Fig. \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In univariable and multivariable analyses, only a dilated bile duct was identified as a risk factor for RBO; however, LBPS itself was not a risk factor for RBO (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eSurgery-related outcomes\u003c/h2\u003e\n \u003cp\u003eThe surgery-related outcomes of the two groups are summarized in Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Surgical resection was successful in 60.0% in the LBPS group and 80.0% in the SEMS group, respectively (P\u0026thinsp;=\u0026thinsp;0.133). Regarding surgical procedures, SSPPD were significantly more common in the LBPS group; however, the curative surgery rates were 91.6% and 72.9% in the LBPS and SEMS groups, respectively, with no significant differences. The median surgery times were 409 and 542 min in the LBPS and SEMS groups, respectively, and were significantly shorter in the LBPS group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Surgery-related AE occurred in 16.6% (2/12: pancreatic fistula in two patients) of the LBPS group and 14.5% (7/48: pancreatic fistula in one patient, biloma in three patients, abscess in one patient, and others in four patients) of the SEMS group (P\u0026thinsp;\u0026gt;\u0026thinsp;0.99). The median time of post-operative hospital stay in the LBPS and SEMS groups was 21 and 27 days, respectively, and tended to be shorter in the LBPS group (P\u0026thinsp;=\u0026thinsp;0.080).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSummary of the results of this study\u003c/h2\u003e \u003cp\u003eThis study compared the clinical outcomes of LBPS and SEMS placement for the preoperative management of biliary obstruction in patients with resectable pancreatic cancer. RBO occurred in 20.0% and 25.0% of the patients in the LBPS and SEMS groups, respectively, which was not significantly different. TRBO was similar in both groups, and in a multivariable analysis examining factors affecting RBO, the type of stent itself was not identified as a significant factor. In contrast, the incidence rates of pancreatitis and cholecystitis were tended to be higher in the SEMS group. Regarding surgery-related outcomes, no significant differences were observed between the two groups in curative surgery rate, intraoperative bleeding volume, and AEs, but the surgical time was significantly shorter in the LBPS group, and the length of hospital stay also tended to be shorter in the LBPS group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eUsefulness and issues of SEMS in preoperative biliary drainage for pancreatic cancer\u003c/h2\u003e \u003cp\u003eIn recent years, NAC has become the mainstream preoperative treatment for pancreatic cancer, and the waiting period before surgery has been extended (\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Before the introduction of NAC, the waiting period for surgery was between 12\u0026ndash;36 days; however, it has been reported that this extended to 72\u0026ndash;165 days after the introduction of NAC (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). PS has traditionally been used as a biliary stent for preoperative drainage in patients with pancreatic cancer, however, SEMS are now recommended considering the extended preoperative period. Kobayashi et al. retrospectively compared the SEMS group (n\u0026thinsp;=\u0026thinsp;21) and PS group (n\u0026thinsp;=\u0026thinsp;22) for preoperative biliary drainage caused by pancreatic cancer (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In the SEMS group, 8-mm fully covered metallic stents were used, whereas in the PS group, 7-Fr plastic stents were used. During the waiting period for surgery, RBO occurred in 4.8% and 95.4% of patients in the SEMS and PS groups, respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The TRBO was significantly longer in the SEMS group than in the PS group. These results suggest that SEMS have a significantly longer patency than PS and are useful as biliary drainage stents for preoperative pancreatic cancer. However, a disadvantage of SEMS is the high incidence of AEs other than RBO, such as pancreatitis and cholecystitis (\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). A retrospective study by Ichikawa et al. compared SEMS (n\u0026thinsp;=\u0026thinsp;45) and PS (n\u0026thinsp;=\u0026thinsp;75) groups for preoperative biliary drainage in patients with pancreatic cancer (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The RBO rate was significantly lower in the SEMS group (24.4% vs. 44.0%, P\u0026thinsp;=\u0026thinsp;0.034), and the TRBO was significantly longer in the SEMS group. However, pancreatitis and cholecystitis were observed in 15.6% and 2.7% (P\u0026thinsp;=\u0026thinsp;0.026) and 6.7% and 0% (P\u0026thinsp;=\u0026thinsp;0.051) in the SEMS and PS groups, respectively. Cote et al. conducted a retrospective study to investigate the risk factors of post-ERCP pancreatitis (PEP) (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). They enrolled 544 patients who underwent stent placement for malignant biliary obstruction, with 248 and 296 patients in the SEMS and PS groups, respectively. The frequency of PEP was significantly higher in the SEMS group (7.3%) than in the PS group (1.3%) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The results showed that the frequency of post-ERCP pancreatitis was significantly higher in the SEMS group. Cao et al. retrospectively examined the risk factors of post-ERCP cholecystitis in 4238 patients who underwent their first ERCP (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Univariate and multivariate analyses identified biliary duct SEMS placement as a risk factor for post-ERCP cholecystitis (OR, 3.66; 95% CI 1.78\u0026ndash;7.54). In the current study, pancreatitis and cholecystitis were observed in 0% vs. 18.3% and 0% vs. 8.3% of the patients in the LBPS and SEMS groups, respectively, and tended to be higher in the SEMS group. These results suggest that SEMS for preoperative biliary drainage of pancreatic cancer has a significantly higher incidence of AEs, such as pancreatitis and cholecystitis, than PS, and there is concern that these AEs may lead to the postponement of NAC or surgery itself. In other words, the relationship between stent patency based on caliber and AEs other than RBO (pancreatitis and cholecystitis) is thought to be a trade-off. In preoperative drainage for pancreatic cancer, a stent strategy that takes into consideration not only RBO but also AEs such as pancreatitis and cholecystitis is required.\u003c/p\u003e \u003cp\u003e \u003cem\u003eOutcomes of preoperative biliary drainage using large-bore PS for pancreatic cancer and its impact on surgery\u003c/em\u003e \u003c/p\u003e \u003cp\u003eThe PS used for preoperative biliary drainage of pancreatic cancer has insufficient patency, and to compensate for this weakness, it is necessary to increase its caliber. Traditionally, a 7-Fr PS has been used primarily for the preoperative drainage of pancreatic cancer, but there have been several reports examining the results of upgrading to a 10-Fr PS. Mandai et al. conducted a multicenter randomized controlled trial (RCT) to compare the clinical outcomes of 10-mm SEMS (n\u0026thinsp;=\u0026thinsp;17) and 10-Fr PS (n\u0026thinsp;=\u0026thinsp;22) for preoperative biliary drainage in pancreatic cancer (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The re-intervention rates were 0% in the SEMS group and 29.4% in the PS group, and patency was significantly longer in the SEMS group than in the PS group. Another RCT by Tamura et al. evaluated a 10-mm SEMS (n\u0026thinsp;=\u0026thinsp;11) and 10-Fr PS (n\u0026thinsp;=\u0026thinsp;11) for preoperative biliary drainage in ancreatic cancer (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). The SEMS group showed a significantly lower rate of RBO (18.2% vs. 72.8%, P\u0026thinsp;=\u0026thinsp;0.015), longer stent patency, and fewer reinterventions for stent dysfunction than the PS group. These results suggest that the caliber of a 10-Fr PS is insufficient for preoperative biliary drainage in patients with pancreatic cancer, and that its patency is significantly shorter than that of the SEMS. However, it should be noted that all these reports had relatively small sample sizes.\u003c/p\u003e \u003cp\u003eThe LBPS used in this study is a new type of plastic stent with a larger diameter of 11.5 Fr. The LBPS has three drainage lumens, and the side holes are larger than those of the conventional PS; therefore, excellent drainage effects can be expected. In the current study, the incidence of RBO during the waiting period for surgery in the LBPS group was comparable to that in the SEMS group, and no significant difference in TRBO was observed between the two groups. Furthermore, the incidence of AEs other than RBO, such as pancreatitis and cholecystitis, was 0% in the LBPS group, whereas the SEMS group had higher rates at 18.3% and 8.3%, respectively. These results suggest that LBPS has the same patency as SEMS and reduces the occurrence of AEs other than RBO.\u003c/p\u003e \u003cp\u003eHowever, there is currently insufficient evidence regarding the effects of PS and SEMS use on surgery. Tamura et al. conducted an RCT to compare the effects of SEMS (n\u0026thinsp;=\u0026thinsp;7) and PS (n\u0026thinsp;=\u0026thinsp;9) placement in pancreatic cancer surgery and found no significant differences between the two groups in terms of operation time, intraoperative blood loss, postoperative hospitalization, or postoperative AEs (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Another RCT by Mandai et al., which compared a SEMS group (n\u0026thinsp;=\u0026thinsp;17) with a PS group (n\u0026thinsp;=\u0026thinsp;22), revealed that the SEMS group had significantly more intraoperative blood loss and AE than the PS group, and the postoperative hospital stay was significantly longer in the SEMS group (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In the current study, no significant differences were observed between the two groups in curative surgery rate, intraoperative bleeding volume, and AEs, but the surgical time was significantly shorter in the LBPS group, and the length of hospital stay also tended to be shorter in the LBPS group. These results suggest that PS, including LBPS, is unlikely to have a negative effect on surgery and may actually have less of an effect than SEMS.\u003c/p\u003e \u003cp\u003e \u003cem\u003e6-mm SEMS for preoperative biliary drainage of pancreatic cancer\u003c/em\u003e \u003c/p\u003e \u003cp\u003eIn recent years, the 6-mm SEMS has attracted attention as a preoperative drainage for pancreatic cancer, considering the trade-off between patency and AEs depending on the stent diameter. Kataoka et al. conducted a retrospective comparative study of the clinical outcomes of a 6-mm SEMS group (n\u0026thinsp;=\u0026thinsp;26) and a PS group (n\u0026thinsp;=\u0026thinsp;25) for preoperative biliary drainage for pancreatic cancer (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The incidence of RBO was significantly lower in the 6-mm SEMS group (7.7%) than that in the PS group (40.0%), and TRBO was significantly longer in the 6-mm SEMS group. The groups did not significantly differ in terms of AEs other than RBO, such as pancreatitis (15.4% vs. 4.0%) and cholecystitis (7.7% vs. 4.0%). Sakai et al. conducted a retrospective comparative study on the outcomes of 6-mm (n\u0026thinsp;=\u0026thinsp;27) and 10-mm SEMS (n\u0026thinsp;=\u0026thinsp;26) in preoperative biliary drainage for pancreatic cancer (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). The RBO rate was 26.9% in the 6-mm SEMS group, which was significantly higher than that in the 10-mm SEMS group (7.7%), and the rate of migration was particularly high at 26.9%. Although there was no significant difference between the two groups in terms of non-RBO AEs, the incidence of pancreatitis was 3.7% vs. 11.5%, and the incidence of cholecystitis was 0% vs. 7.7%, both of which were higher in the 10-mm SEMS group. These results suggest that a 6-mm SEMS can maintain longer patency than a PS and that it can also reduce the occurrence of non-RBO complications such as pancreatitis and cholecystitis compared to a 10-mm SEMS. However, this also suggests that the 6-mm SEMS has a higher RBO owing to migration. In the current study, the 11.5-Fr LBPS demonstrated its usefulness and safety as a stent with patency equivalent to that of a SEMS and suppressed non-RBO AEs such as pancreatitis and cholecystitis; however, there have been no previous reports comparing it with a 6-mm SEMS. In many cases of suspected malignant biliary obstruction due to pancreatic cancer, a PS is often initially placed, if it is replaced with a SEMS after the diagnosis is confirmed, an additional ERCP session is required. However, if an LBPS is placed as the initial stent, additional ERCP is not required to exchange the stent after the diagnosis is confirmed, and NAC treatment can be initiated early. Thus, it is considered that there is great significance in selecting LBPS as the initial stent for preoperative biliary drainage in pancreatic cancer patients. Based on the results of this study, an 11.5-Fr LBPS may be the first choice for preoperative biliary drainage for pancreatic cancer. However, considering that current guidelines recommend SEMS, one option is to actively use it in cases at high risk of post-ERCP pancreatitis or cholecystitis. The American Society for Gastrointestinal Endoscopy (ASGE) and European Society of Gastrointestinal Endoscopy \u003cb\u003e(\u003c/b\u003eESGE) guidelines state that factors that increase the risk of pancreatitis include young age, female gender, and a history of acute pancreatitis or PEP (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). In addition, the risk of developing cholecystitis due to SEMS placement has been reported to include tumor involvement in the orifice of the cystic duct and intragallbladder stones (\u003cspan additionalcitationids=\"CR28 CR29\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). In these cases, 11.5-Fr LBPS is considered a good option to avoid the development of pancreatitis and cholecystitis due to SEMS placement. This study demonstrated the usefulness and safety of LBPS. However, there is currently no established strategy for determining the optimal stent type and diameter for preoperative biliary drainage of pancreatic cancer, and further investigation in larger prospective comparative studies is needed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLimitation\u003c/h2\u003e \u003cp\u003eThis study has several limitations. First, the sample size is small. Second, it was retrospective and conducted at four tertiary care centers, which could potentially have introduced selection bias and reduced its external validity. Third, LBPS was used more frequently during the later phases of the study period. This could have introduced bias in the endoscopic and surgical outcomes, as diagnostic and therapeutic modalities evolved during the study. Fourth, the impact of LBPS and SEMS placement on surgery may not have been fully evaluated using the current items alone.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, 11.5-Fr LBPS had a patency equivalent to that of SEMS and a low incidence of non-RBO AEs, such as pancreatitis and cholecystitis; therefore, it may become the first choice for preoperative biliary drainage in pancreatic cancer. A prospective randomized controlled trial with a larger cohort is required to validate these findings.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAE, adverse event; ERCP, endoscopic retrograde cholangiopancreatography; EST, endoscopic sphincterotomy; EUS-BD, endoscopic ultrasound-guided biliary drainage EUS-FNA, endoscopic ultrasound-guided fine needle aspiration; EUS-FNB, endoscopic ultrasound-guided fine needle biopsy; HR, hazard ratio; IQR, interquartile range; LBPS, large bore plastic stent NAC, neoadjuvant chemotherapy; PEP, post-ERCP pancreatitis; PTBD, percutaneous transhepatic biliary drainage RBO, recurrent biliary obstruction; SEMS, self-expandable metallic stent; TRBO, time to recurrent biliary obstruction; UICC, \u003cstrong\u003eUnion for International Cancer Control;\u003c/strong\u003e 95% CI, 95% confidence interval.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAkinori Maruta wrote the manuscript. Akinori Maruta, Takuya Koizumi, Kota Shimojo, Yosuke Ohashi, Shota Iwata, Hironao Ichikawa, Naoki Mita, Yuhei Iwasa, Mitsuru Okuno,\u0026nbsp;Shinya Uemura, Keisuke Iwata, Tsuyoshi Mukai, Takuji Iwashita, Masahito Shimizu\u0026nbsp;managed the patients. Akinori Maruta took the correspondence. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors declare no conflicts of interest for this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eVersteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA, et al. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J Clin Oncol. 2020;38(16):1763\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurakami Y, Uemura K, Sudo T, Hashimoto Y, Kondo N, Nakagawa N, et al. Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients with borderline resectable pancreatic carcinoma with arterial contact. Cancer Chemother Pharmacol. 2017;79(1):37\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFujii T, Satoi S, Yamada S, Murotani K, Yanagimoto H, Takami H, et al. Clinical benefits of neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreatic head: an observational study using inverse probability of treatment weighting. J Gastroenterol. 2017;52(1):81\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMotoi F, Kosuge T, Ueno H, Yamaue H, Satoi S, Sho M, et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol. 2019;49(2):190\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVersteijne E, van Dam JL, Suker M, Janssen QP, Groothuis K, Akkermans-Vogelaar JM, et al. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. 2022;40(11):1220\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDumonceau JM, Tringali A, Papanikolaou IS, Blero D, Mangiavillano B, Schmidt A, et al. Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline - Updated October 2017. Endoscopy. 2018;50(9):910\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakeda T, Sasaki T, Mie T, Furukawa T, Kanata R, Kasuga A, et al. Novel risk factors for recurrent biliary obstruction and pancreatitis after metallic stent placement in pancreatic cancer. Endosc Int Open. 2020;8(11):E1603-E10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar N, Jena A, Sharma V, Shukla S, Shah J. Outcome of metal vs plastic stents for biliary obstruction in patients with pancreatic carcinoma undergoing neoadjuvant chemoradiotherapy: A systematic review and meta-analysis. J Hepatobiliary Pancreat Sci. 2023;30(4):419\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIshiwatari H, Kobayashi Y, Kawaguchi S, Iwashita T, Kaneko J, Ito J, et al. Assessment of safety and patency of 7-mm covered metal stents for preoperative biliary drainage in pancreatic cancer: Prospective multicenter study. Endosc Int Open. 2025;13:a25031995.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more \"personalized\" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamada S, Fujii T, Takami H, Hayashi M, Iwata N, Kanda M, et al. Evaluation and proposal of novel resectability criteria for pancreatic cancer established by the Japan Pancreas Society. Surgery. 2017;162(4):784\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkusaka T, Nakamura M, Yoshida M, Kitano M, Ito Y, Mizuno N, et al. Clinical Practice Guidelines for Pancreatic Cancer 2022 from the Japan Pancreas Society: a synopsis. Int J Clin Oncol. 2023;28(4):493\u0026ndash;511.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIsayama H, Hamada T, Fujisawa T, Fukasawa M, Hara K, Irisawa A, et al. TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage. Dig Endosc. 2024;36(11):1195\u0026ndash;210.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBassi C, Dervenis C, Butturini G, Fingerhut A, Yeo C, Izbicki J, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138(1):8\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHasegawa S, Endo I, Kubota K. Plastic or self-expandable metal stent: Which is the most suitable for patients with pancreatic head cancer in the upcoming era of neoadjuvant chemotherapy? A review. Dig Endosc. 2022;34(2):297\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKobayashi K, Kobara H, Kamada H, Kohno T, Namima D, Fujita N, et al. Comparison of plastic stent versus metal stent in preoperative biliary drainage for pancreatic head cancer with neoadjuvant chemoradiotherapy. J Hepatobiliary Pancreat Sci. 2021;28(10):856\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIchikawa H, Iwashita T, Iwasa Y, Uemura S, Tezuka R, Okuno M, et al. Covered self-expandable metallic stent versus plastic stent for preoperative endoscopic biliary drainage in patients with pancreatic cancer: a multi-center retrospective cohort study. Scand J Gastroenterol. 2022;57(4):493\u0026ndash;500.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMandai K, Tsuchiya T, Kawakami H, Ryozawa S, Saitou M, Iwai T, et al. Fully covered metal stents vs plastic stents for preoperative biliary drainage in patients with resectable pancreatic cancer without neoadjuvant chemotherapy: A multicenter, prospective, randomized controlled trial. J Hepatobiliary Pancreat Sci. 2022;29(11):1185\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCote GA, Kumar N, Ansstas M, Edmundowicz SA, Jonnalagadda S, Mullady DK, et al. Risk of post-ERCP pancreatitis with placement of self-expandable metallic stents. Gastrointest Endosc. 2010;72(4):748\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCao J, Peng C, Ding X, Shen Y, Wu H, Zheng R, et al. Risk factors for post-ERCP cholecystitis: a single-center retrospective study. BMC Gastroenterol. 2018;18(1):128.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTamura T, Itonaga M, Ashida R, Yamashita Y, Hatamaru K, Kawaji Y, et al. Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study. Dig Endosc. 2021;33(7):1170\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKataoka F, Inoue D, Watanabe M, Fukuda K, Nobusawa T, Umemura K, et al. Efficacy of 6-mm diameter fully covered self-expandable metallic stents in preoperative biliary drainage for pancreatic ductal adenocarcinoma. DEN Open. 2022;2(1):e55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSakai A, Masuda A, Takenaka M, Shiomi H, Omoto S, Yoshida A, et al. Multicenter Comparative Study of 6- and 10-mm Fully Covered Self-Expandable Metal Stents for Malignant Distal Biliary Obstruction During Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Cancer. J Hepatobiliary Pancreat Sci. 2025;32(7):554\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang H, Park CH, Ryu K. Prevention, Detection, and Management of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis. Gut Liver. 2025;19(6):795\u0026ndash;808.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDumonceau JM, Kapral C, Aabakken L, Papanikolaou IS, Tringali A, Vanbiervliet G, et al. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2020;52(2):127\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShimizu S, Naitoh I, Nakazawa T, Hayashi K, Miyabe K, Kondo H, et al. Predictive factors for pancreatitis and cholecystitis in endoscopic covered metal stenting for distal malignant biliary obstruction. J Gastroenterol Hepatol. 2013;28(1):68\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakai Y, Isayama H, Kawakubo K, Kogure H, Hamada T, Togawa O, et al. Metallic stent with high axial force as a risk factor for cholecystitis in distal malignant biliary obstruction. J Gastroenterol Hepatol. 2014;29(7):1557\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakinami M, Murohisa G, Yoshizawa Y, Shimizu E, Nagasawa M. Risk factors for cholecystitis after stent placement in patients with distal malignant biliary obstruction. J Hepatobiliary Pancreat Sci. 2020;27(8):470\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlbunni H, Beran A, Hadaki N, Gromski MA, Al-Haddad M. Risk Factors for Cholecystitis After Self-expandable Metallic Stent Placement for Malignant Distal Biliary Obstruction: A Systematic Review and Meta-analysis. J Clin Gastroenterol. 2025.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"digestive-diseases-and-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ddsj","sideBox":"Learn more about [Digestive Diseases and Sciences](http://link.springer.com/journal/10620)","snPcode":"10620","submissionUrl":"https://submission.nature.com/new-submission/10620/3","title":"Digestive Diseases and Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"large bore plastic stent, preoperative biliary drainage, pancreatic cancer, self-expandable metallic stent, recurrent biliary obstruction","lastPublishedDoi":"10.21203/rs.3.rs-9383752/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9383752/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSelf-expandable metallic stents (SEMS) are recommended for preoperative biliary drainage in patients with pancreatic cancer. However, they are associated with a relatively high incidence of non-recurrent biliary obstruction (RBO) adverse events (AEs), such as pancreatitis and cholecystitis. The 11.5-Fr large-bore plastic stent (LBPS) is a newly developed stent with a larger diameter than conventional plastic stents. The aim of the present study was to compare the clinical outcomes of LBPS and SEMS in preoperative biliary drainage for pancreatic cancer.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively evaluated 80 patients who underwent preoperative biliary drainage for pancreatic cancer between January 2011 and December 2025. Patients were divided into the LBPS and SEMS groups according to the stent placed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eRBO occurred in 20.0% and 25.0% of patients in the LBPS and SEMS groups, respectively, with no significant difference in the time to RBO between the groups. Pancreatitis and cholecystitis were observed in 0% versus 18.3%, and 0% versus 8.3% of patients in the LBPS and SEMS groups, respectively.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe 11.5-Fr LBPS demonstrated patency equivalent to that of SEMS and was associated with a low incidence of non-RBO AEs. Therefore, LBPS may become a preferred option for preoperative biliary drainage in pancreatic cancer.\u003c/p\u003e","manuscriptTitle":"11.5-Fr Large bore plastic stents versus fully covered self-expandable metallic stents for the management of preoperative endoscopic biliary obstruction in pancreatic cancer: a multicenter retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-28 12:55:18","doi":"10.21203/rs.3.rs-9383752/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"238395207295810232058356638172622508721","date":"2026-05-09T13:52:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"224401936150972976064959496839170945183","date":"2026-05-08T16:09:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-19T15:42:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-15T19:31:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-15T07:19:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"Digestive Diseases and Sciences","date":"2026-04-11T01:46:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"digestive-diseases-and-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ddsj","sideBox":"Learn more about [Digestive Diseases and Sciences](http://link.springer.com/journal/10620)","snPcode":"10620","submissionUrl":"https://submission.nature.com/new-submission/10620/3","title":"Digestive Diseases and Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a33a9958-c5b7-44ee-8d61-bc006f0892e8","owner":[],"postedDate":"April 28th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"238395207295810232058356638172622508721","date":"2026-05-09T13:52:36+00:00","index":29,"fulltext":""},{"type":"reviewerAgreed","content":"224401936150972976064959496839170945183","date":"2026-05-08T16:09:42+00:00","index":28,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T12:55:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-28 12:55:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9383752","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9383752","identity":"rs-9383752","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}