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Name of Journal: World Journal of GastroenterologyManuscript NO: 38482Manuscript Type: ORIGINAL ARTICLERetrospective StudyPancreatic stents for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis should be inserted up to the pancreatic body or tailSugimoto M et al. Stents up to the pancreatic body/tail to prevent PEPMitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Naoki Konno, Hiroyuki Asama, Yuki Sato, Hiroki Irie, Ko Watanabe, Jun Nakamura, Hitomi Kikuchi, Yuichi Waragai, Mika Takasumi, Takuto Hikichi, Hiromasa OhiraMitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Naoki Konno, Hiroyuki Asama, Yuki Sato, Hiroki Irie, Ko Watanabe, Jun Nakamura, Hitomi Kikuchi, Yuichi Waragai, Mika Takasumi, Hiromasa Ohira, Department of Gastroenterology, School of Medicine, Fukushima Medical University, Fukushima 960-1247, JapanKo Watanabe, Jun Nakamura, Hitomi Kikuchi, Takuto Hikichi, Department of Endoscopy, Fukushima Medical University Hospital, Fukushima 960-1247, JapanORCID number: Mitsuru Sugimoto (0000-0002-4223-613X); Tadayuki Takagi (0000-0003-0696-5973); Rei Suzuki (0000-0002-4049-0484); Naoki Konno (0000-0001-9830-4317); Hiroyuki Asama (0000-0002-0102-0404); Yuki Sato (0000-0001-8000-0972); Hiroki Irie (0000-0002-4805-6244); Ko Watanabe (0000-0003-3895-7636); Jun Nakamura (0000-0001-6006-1778); Hitomi Kikuchi (0000-0003-0583-1623); Yuichi Waragai (0000-0003-3347-8759); Mika Takasumi (0000-0002-6025-8084); Takuto Hikichi (0000-0002-9815-1557); Hiromasa Ohira (0000-0003-4331-0634).Author contributions: Sugimoto M designed and performed the study; Sugimoto M, Takagi T, and Ohira H analyzed the data; Sugimoto M, Takagi T, and Ohira H wrote the paper; Suzuki R, Konno N, Asama H, Hikichi T, Watanabe K, Nakamura J, Kikuchi H, Waragai Y, Takasumi M, Sato Y, and Irie H provided clinical advice; Hikichi T and Ohira H supervised the rmed consent statement: Patients were not required to provide informed consent for the study because the analysis used anonymous clinical data obtained after each patient agreed to treatment by written consent. For full disclosure, the details of the study are published on the home page of Fukushima Medical University.Conflict-of-interest statement: We have no financial relationships to disclose.Data sharing statement: No additional data are available.Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: source: Unsolicited manuscriptCorrespondence to: Tadayuki Takagi, MD, PhD, Associate Professor, Doctor, Department of Gastroenterology, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima 960-1247, Japan. daccho@fmu.ac.jpTelephone: +81-24-5471202 Fax: +81-24-5472055Received: February 27, 2018Peer-review started: February 27, 2018First decision: March 9, 2018Revised: March 29, 2018Accepted: May 6, 2018 Article in press:Published online:AbstractAIMTo investigate the location to which a pancreatic stent should be inserted to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).METHODSOver a ten-year period at our hospital, 296 patients underwent their first ERCP procedure and had a pancreatic stent inserted; this study included 147 patients who had ERCP performed primarily for biliary investigation and had a pancreatic stent inserted to prevent PEP. We divided these patients into two groups: 131 patients with a stent inserted into the pancreatic head (head group), and 16 patients with a stent inserted up to the pancreatic body or tail (body/tail group). Patient characteristics and ERCP factors were compared between the groups.RESULTSPancreatic amylase isoenzyme (p-AMY) levels in the head group were significantly higher than those in the body/tail group [138.5 (7.0-2086) vs 78.5 (5.0-1266.5), P = 0.03] [median (range)]. No cases of PEP were detected in the body/tail group [head group, 12 (9.2%)]. Of the risk factors for post-ERCP hyperamylasemia (≥ p-AMY median, 131 IU/L), procedure time ≥ 60 min [odds ratio (OR) 2.65, 95%CI: 1.17-6.02, P = 0.02) and stent insertion into the pancreatic head (OR 3.80, 95%CI: 1.12-12.9, P = 0.03) were identified as independent risk factors by multivariate analysis.CONCLUSIONStent insertion up to the pancreatic body or tail reduces the risk of post-ERCP hyperamylasemia and may reduce the risk of PEP.Key words: Pancreatic stent; Endoscopic retrograde cholangiopancreatography; Post-endoscopic retrograde cholangiopancreatography pancreatitis; Post-endoscopic retrograde cholangiopancreatography hyperamylasemia; Pancreatic body or tail? The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.Core tip: We investigated whether the location of the inserted pancreatic stent rather than pancreatic stent length influenced the frequency of post-endoscopic retrograde cholangiopancreatography (ERCP) hyperamylasemia and post-ERCP pancreatitis (PEP). Pancreatic amylase isoenzyme (p-AMY) levels after ERCP were significantly higher in the head group than in the body/tail group. PEP did not occur in the body/tail group. Stent insertion into the pancreatic head was an independent risk factor for hyperamylasemia after ERCP, while stent insertion up to the pancreatic body or tail reduced the risk of post-ERCP hyperamylasemia and may reduce the risk of PEP.Sugimoto M, Takagi T, Suzuki R, Konno N, Asama H, Sato Y, Irie H, Watanabe K, Nakamura J, Kikuchi H, Waragai Y, Takasumi M, Hikichi T, Ohira H. Pancreatic stents for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis should be inserted up to the pancreatic body or tail. World J Gastroenterol 2018; In pressINTRODUCTIONEndoscopic retrograde cholangiopancreatography (ERCP) plays a significant role in endoscopic investigation and treatment for cholangio pancreatic diseases. However, pancreatitis is a serious adverse effect of ERCP. Previous studies have reported that post-ERCP pancreatitis (PEP) occurs in 0.4%-5.6% of casesPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZWllcnRzZW48L0F1dGhvcj48WWVhcj4xOTg3PC9ZZWFy

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ADDIN EN.CITE.DATA [1-8]. Additionally, mortality from PEP has been reported to be 0-0.1%PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GcmVlbWFuPC9BdXRob3I+PFllYXI+MTk5NjwvWWVhcj48

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ADDIN EN.CITE.DATA [4,6-8]. However, pancreatic stents are reported to be useful for preventing PEPL2RhdGU+PC9wdWItZGF0ZXM+PC9kYXRlcz48aXNibj4xNzQ1LTYyMTUgKEVsZWN0cm9uaWMpJiN4

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ADDIN EN.CITE.DATA [23]. However, despite pancreatic ductal stent insertion, PEP has been reported to occur in 1.7%-20% of these casesPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYXdhZ3VjaGk8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFy

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ADDIN EN.CITE.DATA [12-18]. The pancreatic stent that should be used is unclear (size, with flap or without flap, insertion location, etc.); one study reported that a 5-Fr pancreatic stent was easier to insert than a 3-Fr pancreatic stentPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5ab2xvdGFyZXZza3k8L0F1dGhvcj48WWVhcj4yMDExPC9Z

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ADDIN EN.CITE.DATA [24], and another study reported that a 5-Fr pancreatic stent was similarly effective as a 4-Fr pancreatic stent in preventing PEPPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYWhrPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA [25]. An additional report stated that insertion of a pancreatic stent with a diameter > 5 Fr was effective in preventing PEPPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PbHNzb248L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFyPjxS

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b3RlPgB=

ADDIN EN.CITE.DATA [26] compared pancreatic stent lengths (unflapped straight stent, 5 Fr at 3 cm vs 5 Fr at 5 cm) and reported that the PEP rate and the median time until stent migration were lower in the 3-cm group than in the 5-cm group. However, pancreatic sizes varied, and 3-cm or 5-cm pancreatic stents were primarily inserted at the pancreatic head. Olsson et alPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5PbHNzb248L0F1dGhvcj48WWVhcj4yMDE3PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA [22] reported that a pancreatic stent with a length > 5 cm and a diameter > 5 Fr is most effective in preventing PEP. However, the independent efficacy of a longer pancreatic stent to prevent PEP is unknown.Therefore, we investigated whether the location of an inserted pancreatic stent rather than the pancreatic stent length influenced the frequency of post-ERCP hyperamylasemia and PEP.MATERIALS AND METHODSStudy designIn this retrospective study, we compared the efficacy of pancreatic ductal stent insertion between patients with a stent inserted into the pancreatic head and patients with a stent inserted up to the pancreatic body or tail. This study was approved by the Institutional Review Board of Fukushima Medical University.PatientsIn all, 296 patients underwent their first ERCP procedure and had a pancreatic stent inserted at our hospital between January 2007 and November 2017 (Figure 1). Among these patients, 147 who underwent ERCP primarily for biliary investigation and had a stent inserted to prevent PEP were included in this study. We divided these patients into two groups: 131 patients with a stent inserted into the pancreatic head (head group), and 16 patients with a stent inserted up to the pancreatic body or tail (body/tail group). The location of the inserted pancreatic stent was determined by X-ray during ERCP (Figure 2).In total, 149 patients were excluded from this study because 102 patients underwent ERCP primarily to investigate the pancreatic duct, 14 patients had a Vater’s papilla tumor or pancreatic cancer invasion to Vater’s papilla, 13 patients were contracted acute pancreatitis before ERCP, 8 patients had hyperamylasemia before ERCP, 6 patients had part of the stomach resected, 4 patients did not have amylase isozyme measurements after ERCP hyperamylasemia, one patient did not have images from the ERCP, and one patient had malfusion of the pancreaticobiliary ducts.ERCP proceduresAll the patients had an endoscope inserted after they were sufficiently sedated with midazolam. After the endoscope reached the descending part of the duodenum, biliary cannulation was initiated. When a guidewire was passed into the pancreatic duct or contrast media was injected, the guidewire was placed in the main pancreatic duct (MPD) as deep as possible by pancreatography. We injected contrast media as sparingly as possible to confirm MPD placement. After biliary cannulation was achieved, a pancreatic stent was inserted. If biliary cannulation was difficult, we inserted a pancreatic stent and performed a precut of Vater’s papilla. The lengths of the pancreatic stents were determined randomly by the endoscopists. If the patient was diagnosed with PEP or elevated serum pancreatic amylase isoenzyme (p-AMY) (≥ 500 IU/L) with abdominal pain was confirmed, then the pancreatic stent was removed one day after ERCP. In other cases, pancreatic stents with a flap were removed two or three days after ERCP, but pancreatic stents without a flap were not removed. JF260V, JF240, and TJF240 ERCP endoscopes (Olympus, Tokyo, Japan) were used. A Tandem XL (Boston Scientific Japan, Tokyo, Japan), MTW ERCP catheter taper (MTW Endoskopie, Wesel, Germany), or PR-233Q (Olympus) was used as the ERCP catheter. A CleverCut 3V (Boston Scientific Japan, Tokyo, Japan) was used for endoscopic sphincterotomy (EST). An RX Needle Knife (Boston Scientific Japan, Tokyo, Japan) was used to precut Vater’s papilla. A Zimmon 5-Fr, 2-cm single pigtail stent without a flap at the duodenal end (Cook Japan, Tokyo, Japan), a Zimmon 5-Fr, 4-cm single pigtail stent with a flap at the duodenal end (Cook Japan, Tokyo, Japan), a Geenen 5-Fr, 3-cm stent without a flap at the duodenal end (Cook Japan, Tokyo, Japan), or a Geenen 5-Fr, 5-, 7-, or 9-cm stent with a flap at the duodenal end was used as the pancreatic stent. Examined parametersPatient characteristics (age, gender, pancreatic calcification, parapapillary diverticulum, and diameter of the MPD) and ERCP factors (EST, endoscopic papillary balloon dilation (EPBD), precut of Vater’s papilla, procedure time, serum levels of p-AMY, PEP, and pancreatic stent migration within one week) were compared between the head group and the body/tail group. The p-AMY value peaked within one week of ERCP. The level of p-AMY was measured three hours and twenty-four hours after ERCP. If the level of serum amylase was more than three times the normal level 24 h after ERCP, with p-AMY accounting for the majority of the change in serum amylase, we measured p-AMY every day until the serum amylase level decreased to approximately two times the normal level or to a normal level. PEP was diagnosed by hyperamylasemia more than three times the normal level at more than 24 h after ERCP and abdominal painPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Db3R0b248L0F1dGhvcj48WWVhcj4xOTkxPC9ZZWFyPjxS

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ZT4A

ADDIN EN.CITE.DATA [27] (mild: Hospitalization prolonged for 2-3 d; moderate: 4-10 d; and severe: more than 10 d, or pseudocyst requiring intervention (percutaneous drainage or surgery), or hemorrhagic pancreatitis). Pancreatic stent migration was confirmed randomly by X-ray or CT. Statistical analysesKolmogorov-Smirnov tests and Shapiro-Wilk normality tests were used to test normality. Mann-Whitney U tests were used to compare continuous variables. Fisher’s exact tests were used to compare nominal variables. Logistic regression was used to investigate post-ERCP hyperamylasemia factors. A P value < 0.05 was considered to indicate a statistically significant difference. All statistical analyses were performed using the EZR platform (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). More precisely, EZR is a modified version of R commander that was designed to perform functions frequently used in biostatistics ADDIN EN.CITE <EndNote><Cite><Author>Kanda</Author><Year>2013</Year><RecNum>28</RecNum><DisplayText><style face="superscript">[28]</style></DisplayText><record><rec-number>28</rec-number><foreign-keys><key app="EN" db-id="x59sfwd5vvfps7esv2m5feeuptsazwd22pa2" timestamp="1522264203">28</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Kanda, Y.</style></author></authors></contributors><auth-address>Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan. ycanda-tky@umin.ac.jp</auth-address><titles><title>Investigation of the freely available easy-to-use software &apos;EZR&apos; for medical statistics</title><secondary-title>Bone Marrow Transplant</secondary-title><alt-title>Bone marrow transplantation</alt-title></titles><periodical><full-title>Bone Marrow Transplant</full-title><abbr-1>Bone marrow transplantation</abbr-1></periodical><alt-periodical><full-title>Bone Marrow Transplant</full-title><abbr-1>Bone marrow transplantation</abbr-1></alt-periodical><pages>452-8</pages><volume>48</volume><number>3</number><edition>2012/12/05</edition><keywords><keyword>Biomedical Research</keyword><keyword>Data Interpretation, Statistical</keyword><keyword>Hematopoietic Stem Cell Transplantation</keyword><keyword>Humans</keyword><keyword>Proportional Hazards Models</keyword><keyword>Software/ standards</keyword></keywords><dates><year>2013</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1476-5365 (Electronic)&#xD;0268-3369 (Linking)</isbn><accession-num>23208313</accession-num><urls></urls><custom2>PMC3590441</custom2><electronic-resource-num>10.1038/bmt.2012.244</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[28].RESULTSPatient characteristics were not significantly different between the two groups (Table 1). Regarding aspects of the ERCP procedures, the p-AMY levels after ERCP in the head group were significantly higher than those in the body/tail group [138.5 (7.0-2086) IU/L vs 78.5 (5.0-1266.5), P = 0.03] [median (range)] (Table 2). Other factors were not different between the two groups, and PEP did not occur in the body/tail group. However, PEP occurred in 12 patients in the head group (mild 2; moderate 8; and severe 2).Regarding the risk factors of post-ERCP hyperamylasemia (≥ p-AMY median, 131 IU/L), age ≥ 71 years, parapapillary diverticulum, stent insertion into the pancreatic head, and procedure time ≥ 60 min were identified as significant factors in the univariate analysis (factors with P < 0.15 were selected for multivariate analysis) (Table 3). Logistic regression with backward stepwise selection was performed using these four items, and the independent risk factors included procedure time ≥ 60 min [odds ratio (OR) 2.65, 95%CI: 1.17-6.02, P = 0.02] and stent insertion into the pancreatic head (OR 3.80, 95%CI: 1.12-12.9, P = 0.032) (Table 4).DISCUSSIONIn this study, we investigated how far a pancreatic stent should be inserted. We compared several factors between the head group and the body/tail group. P-AMY levels after ERCP were significantly higher in the head group than in the body/tail group. PEP did not occur in the body/tail group. Stent insertion into the pancreatic head was an independent risk factor for hyperamylasemia after ERCP.Several reports are available regarding the diameter of pancreatic stents. Lawrence et alPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXdyZW5jZTwvQXV0aG9yPjxZZWFyPjIwMDc8L1llYXI+

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ADDIN EN.CITE.DATA [29] reported that 3-Fr pancreatic stents passed spontaneously and did not induce changes in the pancreatic duct. Zolotarevsky et alPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5ab2xvdGFyZXZza3k8L0F1dGhvcj48WWVhcj4yMDExPC9Z

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ADDIN EN.CITE.DATA [24] reported that placement of a 5-Fr pancreatic stent was easier, faster, and required fewer wires compared to a 3-Fr pancreatic stent. Pahk et alPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QYWhrPC9BdXRob3I+PFllYXI+MjAxMTwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA [25] reported that 4-Fr pancreatic stents migrated more frequently than 5-Fr pancreatic stents; therefore, the need for additional endoscopy to retrieve the pancreatic stent was reduced by using a 4-Fr pancreatic stent. However, PEP was no less common with the slimmer stents in these reports. This report showed that pancreatic stent placement in the pancreatic body or tail could reduce the rates of post-ERCP hyperamylasemia and PEP. Difficulty with pancreatic duct drainage leads to proteinase activation, which exacerbates pancreatitis ADDIN EN.CITE <EndNote><Cite><Author>Kingsnorth</Author><Year>1997</Year><RecNum>30</RecNum><DisplayText><style face="superscript">[30]</style></DisplayText><record><rec-number>30</rec-number><foreign-keys><key app="EN" db-id="x59sfwd5vvfps7esv2m5feeuptsazwd22pa2" timestamp="1522264203">30</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="bold" font="default" size="100%">Kingsnorth, A.</style></author></authors></contributors><auth-address>Plymouth Postgraduate Medical School, Derriford Hospital, Devon.</auth-address><titles><title>Role of cytokines and their inhibitors in acute pancreatitis</title><secondary-title>Gut</secondary-title><alt-title>Gut</alt-title></titles><periodical><full-title>Gut</full-title><abbr-1>Gut</abbr-1></periodical><alt-periodical><full-title>Gut</full-title><abbr-1>Gut</abbr-1></alt-periodical><pages>1-4</pages><volume>40</volume><number>1</number><edition>1997/01/01</edition><keywords><keyword>Acute Disease</keyword><keyword>Cytokines/antagonists &amp; inhibitors/ physiology</keyword><keyword>Humans</keyword><keyword>Inflammation/etiology</keyword><keyword>Pancreatitis/ etiology</keyword></keywords><dates><year>1997</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>0017-5749 (Print)&#xD;0017-5749 (Linking)</isbn><accession-num>9155566</accession-num><urls></urls><custom2>PMC1026998</custom2><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[30]. Pancreatic stent placement up to the pancreatic body or tail could allow greater pancreatic duct drainage than stent placement in the pancreatic head. Therefore, stent placement up to the pancreatic body or tail may reduce the risks of PEP and post-ERCP hyperamylasemia. In addition, no pancreatic stent migration was observed in the body/tail group. Therefore, the risk of pancreatic stent obstruction by contact with the duodenal wall was considered to be low.This study has some limitations. First, this was a retrospective study with a small number of patients at a single institution. In addition, we generally insert stents into the pancreatic head as described in past reports; we only recently began inserting pancreatic stents up to the body or tail of the pancreas. Therefore, the number of patients in the body/tail group was small. We hope to conduct larger prospective studies to verify the findings of this study. However, we performed a multivariate analysis including post-ERCP serum p-AMY levels and were able to identify the risk factors for post-ERCP hyperamylasemia. Second, many patients were excluded from this study. However, the amount of contrast media used in 102 patients to investigate the pancreatic duct by pancreatography was much higher than the target amount of this study. The risk of PEP in the 102 excluded patients was very different from that in the general population, as many of these excluded patients had chronic pancreatitis. In addition, many patients with pancreatic stricture underwent pancreatic stenting as treatment rather than for the prevention of PEP. Therefore, the patients included in the present study and the 102 patients excluded from the study could not be compared. Third, due to the retrospective nature of this study, ERCP procedures were not performed by specific endoscopists. In this study, ERCP was performed by specialists in pancreaticobiliary endoscopy who had experience in performing at least 2000 ERCP procedures or by trainees under the guidance of these specialists. Therefore, the quality of the ERCP procedure was considered to be consistent. Fourth, unflapped stents (Geenen 5 Fr, 3 cm and Zimmon 5 Fr, 2 cm) were used in only the head group. Consequently, the stent migration rate was higher in the head group than in the body/tail group. However, in past reports, decreased incidence of spontaneous pancreatic stent migration did not subsequently result in increased incidence of PEPPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGFoYWw8L0F1dGhvcj48WWVhcj4yMDA5PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA [25,26,31]. In addition, using an unflapped stent was considered disadvantageous in the head group.In conclusion, stent insertion up to the pancreatic body or tail reduced the incidence of post-ERCP hyperamylasemia and may reduce the incidence of PEP. ARTICLE HIGHLIGHTS Research backgroundPancreatic stents are reported to be useful for preventing pancreatitis (PEP). Research motivationWe wanted to determine the appropriate length of a pancreatic stent for preventing PEP.Research objectives To investigate whether a stent should be inserted into the pancreatic head, body, or tail to prevent PEP.Research methodsPatient characteristics and endoscopic retrograde cholangiopancreatography (ERCP) factors were compared between 131 patients with a stent inserted into the pancreatic head (head group) and 16 patients with a stent inserted up to the pancreatic body or tail (body/tail group).Research resultsPancreatic amylase isoenzyme (p-AMY) levels after ERCP were significantly higher in the head group than in the body/tail group. PEP did not occur in the body/tail group. Stent insertion into the pancreatic head was an independent risk factor for hyperamylasemia after ERCP.Research conclusionsStent insertion up to the pancreatic body or tail reduced the incidence of post-ERCP hyperamylasemia and may reduce the incidence of PEP.Research perspectivesProphylactic stent insertion up to the pancreatic body or tail may be the main method for preventing PEP. We hope that a future prospective, multicenter study will confirm the conclusion of this study.ACKNOWLEDGMENTSI am grateful to the staff at the Department of Gastroenterology of Fukushima Medical University School of Medicine, the medical staff in the Department of Endoscopy at Fukushima Medical University Hospital, and the medical staff of the Gastroenterology Ward at Fukushima Medical University Hospital. REFERENCES1 Reiertsen O, Skj?t? J, Jacobsen CD, Rosseland AR. Complications of fiberoptic gastrointestinal endoscopy--five years' experience in a central hospital. 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Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013; 48: 452-458 [PMID: 23208313 DOI: 10.1038/bmt.2012.244]29 Lawrence C, Cotton PB, Romagnuolo J, Payne KM, Rawls E, Hawes RH. Small prophylactic pancreatic duct stents: an assessment of spontaneous passage and stent-induced ductal abnormalities. Endoscopy 2007; 39: 1082-1085 [PMID: 17886200 DOI: 10.1055/s-2007-966815]30 Kingsnorth A. Role of cytokines and their inhibitors in acute pancreatitis. Gut 1997; 40: 1-4 [PMID: 9155566]31 Chahal P, Tarnasky PR, Petersen BT, Topazian MD, Levy MJ, Gostout CJ, Baron TH. Short 5Fr vs long 3Fr pancreatic stents in patients at risk for post-endoscopic retrograde cholangiopancreatography pancreatitis. Clin Gastroenterol Hepatol 2009; 7: 834-839 [PMID: 19447196 DOI: 10.1016/j.cgh.2009.05.002]P-Reviewer: Gonzalez-Ojeda AG, Gupta R, Han JH, Isik ARDA, Luglio G, Lorenzo-Zuniga V, Rabago LR, Tallon-Aguilar L S-Editor: Wang XJ L-Editor: E-EditorSpecialty type: Gastroenterology and hepatologyCountry of origin: JapanPeer-review report classificationGrade A (Excellent): AGrade B (Very good): B, B, B, BGrade C (Good): C, CGrade D (Fair): DGrade E (Poor): 0Figure 1 Subjects in this study. A total of 296 patients underwent their first ERCP procedure and had a pancreatic stent inserted at our hospital between January 2007 and November 2017. Among these patients, 147 who received ERCP primarily for biliary investigation and had a stent inserted to prevent post-ERCP pancreatitis were included in this study. We divided these patients into two groups: 131 patients with a stent inserted into the pancreatic head (head group), and 16 patients with a stent inserted up to the pancreatic body or tail (body/tail group). ERCP: Endoscopic retrograde cholangiopancreatography.Figure 2 Inserted pancreatic stent. A: A pancreatic stent (Geenen 5 Fr, 5 cm) was inserted into the pancreatic head; B: A pancreatic stent (Geenen 5 Fr, 7 cm) passed the angle between the pancreatic head and body and was inserted up to the pancreatic body or tail. Table 1 Comparison of patient demographic and clinical characteristics n (%)Head group(n = 131)Body/tail group(n = 16)P valueAge, median (range), yr71.0 (29-97)66.5 (26-81)0.052Male/female69/6211/50.29Pancreatic calcification4 (3.1)11 (6.3)0.45Parapapillary diverticulum38 (29.5)25 (31.2)1.0Diameter of the MPD, median (range), mm3.1 (0.7-22.0)3.7 (1.5-13.8)0.15DiagnosisLeft hepatic duct extension1Biliary strictureBenign5MalignantPancreatic cancer247Biliary tract cancer333Hepatocellular carcinoma3Obstructive jaundice by metastatic cancerBarrett’s esophageal cancer1Colon cancer4Gastric cancer2Uterine cancer1Bladder cancer1Ovarian cancer1Suppression of lymph node swelling1Central bile duct stone474Primary sclerosing cholangitis11Gallbladder adenomyosis3IPNB1Sphincter of Oddi dysfunction1Biliary cysts1Lemmel syndrome11Data from four cases were not available; 2Data from two cases were not available. MPD: Main pancreatic duct.Table 2 Comparison of ERCP procedures n (%)Head group(n = 131)Body/tail group(n = 16)P valueEST98 (75.4)15 (93.8)0.12Precut of Vater’s papilla43 (33.1)5 (31.3)1EPBD8 (6.2)0 (0)0.6Pancreatic stent migration within 1 wk26 (19.8)0 (0)0.076Procedure time, median (range), min60 (20-150)160 (40-120)20.31Type of stentZimmon 5 Fr, 2 cm3Zimmon 5 Fr, 4 cm1Geenen 5 Fr, 3 cm59Geenen 5 Fr, 5 cm58Geenen 5 Fr, 7 cm1112Geenen 5 Fr, 9 cm4p-AMY after ERCP, median (range), IU/L138.5 (7.0-2086)378.5 (5.0-1266.5)0.03PEP12 (9.2)0 (0)0.363Mild2Moderate8Severe21 Data from three cases were not available; 2 Data from one case were not available; 3Pancreatic amylase data from seven cases were not available, but the level of serum amylase was not elevated. EPBD: Endoscopic papillary balloon dilation; p-AMY: Pancreatic amylase isoenzyme; PEP: Pancreatitis.Table 3 Risk factors of post-endoscopic retrograde cholangiopancreatography hyperamylasemia (≥ pancreatic amylase isoenzyme median, 131 IU/L) (univariate analysis) np-AMY < 131 IU/L1(n = 70)p-AMY ≥ 131 IU/L1(n = 70)P valueAge (≥ 71 yr)29410.063Gender (male/female)40/3035/350.50Pancreatic calcification321Parapapillary diverticulum27160.043MPD ≥ 3.2 mm36361.0EST52550.69EPBD331.0Precut of Vater’s papilla18260.20Stent inserted pancreatic head58660.06Pancreatic stent migration within a week11121.0Procedure time ≥ 60 min45570.0481 Pancreatic amylase data were not available in seven cases, but the level of serum amylase was not elevated. MPD: Main pancreatic duct; EPBD: Endoscopic papillary balloon dilation.Table 4 Risk factors for post-endoscopic retrograde cholangiopancreatography hyperamylasemia (≥ pancreatic amylase isoenzyme median, 131 IU/L) (multivariate analysis by logistic regression with backward stepwise selection)OR95%CIP valueProcedure time ≥ 60 min2.651.17-6.020.020Stent insertion into the pancreatic head3.801.12-12.90.032 ................
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