Publications by authors named "Atsuhiro Masuda"

87 Publications

Estimation of pancreatic fibrosis and prediction of postoperative pancreatic fistula using extracellular volume fraction in multiphasic contrast-enhanced CT.

Eur Radiol 2021 Oct 12. Epub 2021 Oct 12.

Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Objective: To investigate the diagnostic performance of the extracellular volume (ECV) fraction in multiphasic contrast-enhanced computed tomography (CE-CT) for estimating histologic pancreatic fibrosis and predicting postoperative pancreatic fistula (POPF).

Methods: Eighty-five patients (49 men; mean age, 69 years) who underwent multiphasic CE-CT followed by pancreaticoduodenectomy with pancreaticojejunal anastomosis between January 2012 and December 2018 were retrospectively included. The ECV fraction was calculated from absolute enhancements of the pancreas and aorta between the precontrast and equilibrium-phase images, followed by comparisons among histologic pancreatic fibrosis grades (F0‒F3). The diagnostic performance of the ECV fraction in advanced fibrosis (F2‒F3) was evaluated using receiver operating characteristic curve analysis. Multivariate logistic regression analysis was used to evaluate the associations of the risk of POPF development with patient characteristics, histologic findings, and CT imaging parameters.

Results: The mean ECV fraction of the pancreas was 34.4% ± 9.5, with an excellent intrareader agreement of 0.811 and a moderate positive correlation with pancreatic fibrosis (r = 0.476; p < 0.001). The mean ECV fraction in advanced fibrosis was significantly higher than that in no/mild fibrosis (44.4% ± 10.8 vs. 31.7% ± 6.7; p < 0.001), and the area under the receiver operating characteristic curve for the diagnosis of advanced fibrosis was 0.837. Twenty-two patients (25.9%) developed clinically relevant POPF. Multivariate logistic regression analysis demonstrated that the ECV fraction was a significant predictor of POPF.

Conclusions: The ECV fraction can offer quantitative information for assessing pancreatic fibrosis and POPF after pancreaticojejunal anastomosis.

Key Points: • There was a moderate positive correlation of the extracellular volume (ECV) fraction of the pancreas in contrast-enhanced CT with the histologic grade of pancreatic fibrosis (r = 0.476; p < 0.001). • The ECV fraction was higher in advanced fibrosis (F2‒F3) than in no/mild fibrosis (F0‒F1) (p < 0.001), with an AUC of 0.837 for detecting advanced fibrosis. • The ECV fraction was an independent risk factor for predicting subclinical (odds ratio, 0.81) and clinical (odds ratio, 0.80) postoperative pancreatic fistula.
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http://dx.doi.org/10.1007/s00330-021-08255-4DOI Listing
October 2021

A Prospective Multicenter Randomized Feasibility Trial of Double-guidewire Techniques for Difficult Biliary Cannulation Comparing a New Double-guidewire-supported Sphincterotome (MagicTome) to a Conventional Device.

Intern Med 2021 Aug 6. Epub 2021 Aug 6.

Center for Clinical Research and Advanced Medicine Establishment, Shiga University of Medical Science, Japan.

Purpose To evaluate the effectiveness and safety of the double-guidewire technique (DGT) using a new double-guidewire-supported sphincterotome (MagicTome) for patients who required endoscopic retrograde cholangiopancreatography (ERCP) for biliary cannulation. Methods This prospective multicenter randomized feasibility trial involved patients with difficult biliary cannulation at any of the three study sites from June 2017 to October 2018. Patients were assigned to the DGT with MagicTome (MDGT) initially performed group and the conventional DGT (CDGT) initially performed group. The success rates of biliary cannulation by MDGT and CDGT and the ERCP-related complications were evaluated. Results Twenty-eight patients were included in this study. No significant difference was observed in the success rates of first attempts and crossover attempts between the groups (p=0.69 and p=1.00). Furthermore, no significant difference was observed in the success rate of biliary cannulation between MDGT and CDGT (62.5% and 75.0%, respectively; p=0.48). CDGT was successful in two of four patients with malignant biliary obstruction. MDGT was successful in all four patients with malignant biliary obstruction, including the two for whom CDGT was unsuccessful. Post-ERCP pancreatitis occurred in only one MDGT case. Conclusion MDGT is safe for biliary cannulation and can be used in cases where biliary cannulation by CDGT is difficult.
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http://dx.doi.org/10.2169/internalmedicine.7367-21DOI Listing
August 2021

Clinical management for malignant afferent loop obstruction.

World J Gastrointest Oncol 2021 Jul;13(7):684-692

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan.

Afferent loop obstruction (ALO) is defined as duodenal or jejunal mechanical obstruction at the proximal anastomosis site of a gastrojejunostomy. With advances in chemotherapy, the incidence of malignant ALO is increasing. Malignant ALO can be complicated by ischemia, gangrenous bowel, pancreatitis, and ascending cholangitis. Moreover, the general condition of patients with recurrent cancer is often poor. Therefore, accurate and rapid diagnosis and minimally invasive treatments are required. However, no review articles on the diagnosis and treatment of malignant ALO have been published. Through literature searching, we reviewed related articles published between 1959 and 2020 in the PubMed database. Herein, we present recent advances in the diagnosis and treatment of malignant ALO and describe future perspectives. Endoscopic transluminal self-expandable metal stent (SEMS) placement is considered the standard treatment for malignant ALO, as this procedure is well established and less invasive. However, with the development of interventional endoscopic ultrasound (EUS) in recent years, the usefulness of EUS-guided gastrojejunostomy has been reported. Moreover, through indirect comparison, this approach has been reported to be superior to transluminal SEMS placement. It is expected that a safer and less invasive treatment method will be established through the continued advancement and innovation of interventional endoscopy techniques.
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http://dx.doi.org/10.4251/wjgo.v13.i7.684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299933PMC
July 2021

Combined bridging and antegrade stent placement during transmural treatment for malignant hilar biliary obstruction in a patient with surgically altered anatomy.

VideoGIE 2021 Feb 12;6(2):87-89. Epub 2020 Nov 12.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

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http://dx.doi.org/10.1016/j.vgie.2020.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859656PMC
February 2021

Comparison of endoscopic ultrasound-guided choledochoduodenostomy and endoscopic retrograde cholangiopancreatography in first-line biliary drainage for malignant distal bile duct obstruction: A multicenter randomized controlled trial.

Medicine (Baltimore) 2021 Mar;100(12):e25268

Clinical Study Support Center, Wakayama Medical University, Wakayama.

Introduction: In patients with malignant distal bile duct obstruction and normal gastrointestinal anatomy, endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is indicated when endoscopic retrograde cholangiopancreatography (ERCP) fails. The ERCP drainage route passes through the tumor, whereas the EUS-CDS route does not. Therefore, EUS-CDS is expected to have a longer stent patency than ERCP. However, for first-line biliary drainage, it remains unclear whether EUS-CDS or ERCP is superior in terms of stent patency. To reduce the frequency of highly adverse events (AEs) such as bile peritonitis or stent migration following EUS-CDS, we developed an antimigration metal stent with a thin delivery system for tract dilatation. This study is designed to assess whether EUS-CDS with this novel stent is superior to ERCP with a traditional metal stent in terms of stent patency when the two techniques are used for first-line drainage of malignant distal biliary obstruction.

Methods/design: This study is a multicenter single-blinded randomized controlled trial (RCT) involving 95 patients in four tertiary centers. Patients with malignant distal biliary obstruction that is unresectable or presents a very high surgical risk and who pass the inclusion and exclusion criteria will be randomized to EUS-CDS or ERCP in a 1:1 proportion. The primary endpoint is the stent patency rate 180 days after stent insertion. Secondary outcomes include the rates of technical success, clinical success, technical success in cases not requiring fistulous-tract dilation (only EUS-CDS group), procedure-related AEs, re-intervention success, patients receiving post-drainage chemotherapy, procedure time, and overall survival time.

Discussion: If EUS-CDS is superior to ERCP in terms of stent patency and safety for the first-line drainage of malignant distal biliary obstruction, it is expected that the first-line drainage method will be changed from ERCP to EUS-CDS, and that interruption of chemotherapy due to stent dysfunction can be avoided.

Trial Registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000041343. Registered on August 6, 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047201Version number: 1.2, December 7, 2020.
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http://dx.doi.org/10.1097/MD.0000000000025268DOI Listing
March 2021

EUS-guided cholecystoduodenostomy using novel dumbbell-shaped fully covered metal stent (with video).

J Hepatobiliary Pancreat Sci 2021 May 9;28(5):e19-e20. Epub 2021 Apr 9.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Highlight Atalla and colleagues present a novel dumbbell-shaped fully covered self-expandable metal stent which, with its anti-migration property and relatively lower cost, is a feasible and cost-effective option as an alternative to lumen-apposing metal stents for endoscopic ultrasound-guided transduodenal gallbladder drainage for acute cholecystitis in patients who are ineligible for surgery.
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http://dx.doi.org/10.1002/jhbp.942DOI Listing
May 2021

Pancreatic metastasis of renal cell carcinoma filling into the duct of Santorini.

Clin J Gastroenterol 2021 Jun 6;14(3):905-909. Epub 2021 Mar 6.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

A 78-year-old man who underwent right nephrectomy for renal cell carcinoma (RCC) 18 years ago visited our hospital complaining of abdominal pain. Imaging revealed that the pancreatic head tumor obstructed the Santorini duct. We suspected a pancreatic intraductal tumor, such as an intraductal tubulopapillary neoplasm or intraductal papillary mucinous neoplasm. Thus, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings confirmed the diagnosis of metastatic RCC. Herein, we report a case of pancreatic metastasis of an RCC that presented with a tumor in the pancreatic duct.
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http://dx.doi.org/10.1007/s12328-021-01369-8DOI Listing
June 2021

Non-Alcoholic Fatty Liver Disease Is Strongly Associated with Smoking Status and Is Improved by Smoking Cessation in Japanese Males: A Retrospective Study.

Kobe J Med Sci 2020 Nov 17;66(3):E102-E112. Epub 2020 Nov 17.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Cigarette smoking is known to be a significant risk factor associated with non-alcoholic fatty liver disease (NAFLD). We aimed to examine the association between smoking status and the severity of fatty liver with regard to sex and smoking cessation.

Methods: In total, 13,466 subjects (6,642 males and 6,824 females) who had undergone abdominal ultrasonography for health check-up, multivariable logistic regression analysis was retrospectively conducted to assess the association between smoking status and the prevalence of NAFLD stratified by sex after adjusting for other potential confounders.

Results: Male sex (odds ratio [OR] 3.27, 95% confidence interval [CI] 3.00-3.57) and smoking history (former smoker: OR 1.23, 95% CI 1.10-1.38, current smoker: OR 1.31, 95% CI 1.17-1.47) were significantly associated with NAFLD. In males with a smoking history, an increased pack-year was strongly associated with the prevalence and severity of NAFLD (prevalence of moderate to severe fatty liver: Pack-year from 0.01 to 9.99, 21.3%; Pack-year from 10.00 to 19.99, 27.2%; Pack-year ≥20.00, 33.7%; P<0.0001), although the prevalence of moderate to severe fatty liver was inversely associated with the duration of smoking cessation (more than 10 years vs. within 5 years, OR 0.71, 95% CI 0.53-0.96). In female subjects, light current smoking was negatively associated with NAFLD (current smoker with a pack-year from 0.01 to 9.99 vs. never smoker, OR 0.41, 95% CI 0.19-0.76).

Conclusions: Smoking status and pack-year were strongly associated with the prevalence and severity of NAFLD, especially in Japanese males. However, smoking cessation improved NAFLD in this population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837663PMC
November 2020

Acute pancreatitis in intraductal papillary mucinous neoplasms correlates with pancreatic volume and epithelial subtypes.

Pancreatology 2021 Jan 20;21(1):138-143. Epub 2020 Nov 20.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with acute pancreatitis (AP) in some cases, however its causes have not been fully elucidated. We investigated the association of the incidence of AP with epithelial subtypes and pancreatic volume in IPMN.

Methods: This retrospective study included 182 consecutive surgically resected IPMN patients between January 2000 and December 2018. The relationship between the incidence of AP and epithelial subtypes of IPMN and pancreatic volume was investigated. Epithelial subtypes of IPMN were classified into gastric (G type: N = 116), intestinal (I type: N = 49), pancreatobiliary (PB type: N = 14), and oncocytic types (O type: N = 3). Pancreatic volume of the contrast-enhanced computed tomography scan was measured using Ziostation2 software. Histological pancreatic parenchymal atrophy was also evaluated.

Results: AP occurred more frequently in I-types (I-type vs. G-type, 22.4% [11/49] vs 3.4% [4/116], P = 0.003) and PB-types (PB type vs. G-type, 35.7% [5/14] vs. 3.4% [4/116], P = 0.007) in comparison with G-types, which constituted the majority of the resected IPMNs. AP occurred more frequently in I-type patients with high pancreatic volumes (I-type with high pancreatic volume vs. I-type with low pancreatic volume, 37.0% [10/27] vs. 4.7% [1/21], P = 0.02). However, histological atrophy did not show an additional influence on the association between the incidence of AP and epithelial subtypes. The elevation of serum pancreatic enzymes was not significantly related to epithelial subtypes.

Conclusion: Epithelial subtypes and the degree of pancreatic volume may be closely associated with the incidence of AP in IPMN.
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http://dx.doi.org/10.1016/j.pan.2020.11.005DOI Listing
January 2021

An autopsy case of severe acute pancreatitis induced by administration of pazopanib following nivolumab.

Pancreatology 2021 Jan 5;21(1):21-24. Epub 2020 Nov 5.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.

Drug-induced pancreatitis is often mild to moderate in severity, but severe and even fatal cases can occur. Here, we report a 74-year-old woman undergoing chemotherapy for recurrent renal cell carcinoma, who presented with abdominal pain after administration of pazopanib following nivolumab and was diagnosed with severe acute pancreatitis. Administration of methylprednisolone and conservative treatment were initiated, but clinical findings and laboratory tests rapidly worsened. When she died, an autopsy was performed. The autopsy findings suggested the possibility of pancreatitis as immune-related adverse events. To the best of our knowledge, no fatal cases of acute pancreatitis due to nivolumab or pazopanib have been reported. We considered that the effects of nivolumab were sustained in the pancreas, and pazopanib administration might have worsened the toxicity.
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http://dx.doi.org/10.1016/j.pan.2020.11.002DOI Listing
January 2021

Clinical outcome of conservatively managed pancreatic intraductal papillary mucinous neoplasms with mural nodules and main duct dilation.

J Gastroenterol 2021 03 28;56(3):285-292. Epub 2020 Oct 28.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0071, Japan.

Background: Surgical resection of intraductal papillary mucinous neoplasm (IPMN) is strongly recommended for patients exhibiting high-risk stigmata (HRS). However, determining surgical indications for elderly patients with comorbidities is challenging, as clinical outcomes are not well characterized. This multicenter observational study elucidated the clinical outcomes of patients with IPMN exhibiting HRS who did not undergo surgery.

Methods: This study enrolled 101 IPMN patients exhibiting HRS with follow-up observations at 11 hospitals in Japan (2011-2016). The median observation period was 37 months (maximum: 86 months). Primary outcomes were estimated 5-year overall survival (OS) and disease-specific survival (DSS). Survival was also stratified based on HRS features.

Results: Of 101 patients, 32 (31.7%) had the main pancreatic duct (MPD) measuring ≥ 10 mm and 80 (79.2%) had mural nodules measuring ≥ 5 mm. The estimated 5-year OS and DSS were 74% and 91%, respectively. In the stratified analysis, the co-presence of MPD ≥ 10 mm and mural nodules ≥ 5 mm or mural nodule ≥ 10 mm were related to worse 5-year DSS (MPD ≥ 10 mm and mural nodules ≥ 5 mm vs other characteristics: 60% vs 95%, log-rank test: p = 0.049; mural nodules ≥ 10 mm vs < 10 mm: 77% vs 95%, log-rank test: p = 0.003).

Conclusions: The estimated 5-year DSS of conservatively managed IPMN patients with mural nodules and main duct dilation was 91%. Only IPMN patients with plural HRS or large nodule formation might have an increased mortality risk. This is an important insight that can help facilitate appropriate clinical decision-making, especially in the elderly or high-surgical risk IPMN patients.
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http://dx.doi.org/10.1007/s00535-020-01739-yDOI Listing
March 2021

Influence of sex on the association between body mass index and frequency of upper gastrointestinal symptoms.

JGH Open 2020 Oct 5;4(5):937-944. Epub 2020 Jun 5.

Division of Gastroenterology, Department of Internal Medicine Kobe University Graduate School of Medicine Kobe Japan.

Background And Aim: Upper gastrointestinal symptoms (UGSs), including reflux and dyspeptic symptoms (postprandial distress syndrome [PDS] and epigastric pain syndrome [EPS]), affect health-related quality of life. However, the influence of sex on the relationship between body mass index (BMI) and UGSs remains controversial. This study investigates the influence of sex on this association in healthy subjects.

Methods And Results: We utilized the database of a prospective, multicenter, cohort study of 7112 subjects who underwent upper endoscopy for health screening. A multivariable logistic regression analysis was conducted to assess the association between BMI and UGSs stratified by sex, adjusting for clinical features. The influence of sex on the association between the overlapping of UGSs and BMI in symptomatic subjects was also investigated. Reflux symptoms were significantly associated with high BMI (multivariable odds ratio [OR] 1.36; 95% confidence interval [CI] 1.10-1.67, = 0.004). PDS symptoms were significantly associated with low BMI (OR 2.37; 95% CI 1.70-3.25;  < 0.0001), but EPS symptoms were not associated with BMI. The association between reflux symptoms and higher BMI was limited to men (men: OR 1.40; 95% CI 1.10-1.77; = 0.005, women: = 0.40). sex did not influence the association between the presence of PDS symptoms and lower BMI. The percentage of overlapping of all three symptoms (reflux, PDS, and EPS) was higher in women than in men (19.9% [58/292] 10.5% [49/468], = 0.0002).

Conclusions: The influence of BMI on the presence of UGSs was significantly different according to sex in this large-scale cohort.
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http://dx.doi.org/10.1002/jgh3.12368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578286PMC
October 2020

Prospective Study Using Plasma Apolipoprotein A2-Isoforms to Screen for High-Risk Status of Pancreatic Cancer.

Cancers (Basel) 2020 Sep 14;12(9). Epub 2020 Sep 14.

AMED-CREST, AMED, Tokyo 1000004, Japan.

Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) has been identified as a minimally invasive biomarker for detecting pancreatic cancer (PC) and high-risk (HR) individuals for PC. To establish an efficient enrichment strategy for HR, we carried out a plasma apoA2-ATQ/AT level-based prospective screening study among the general population. The subjects for the screening study were recruited at six medical check-up facilities in Japan between October 2015 and January 2017. We evaluated the positive predictive value (PPV) of the plasma apoA2-ATQ/AT level of ≤35 μg/mL for detecting PC and HR. Furthermore, we prospectively confirmed its diagnostic accuracy with another post-diagnosis population in a cross-sectional study. We enrolled 5120 subjects in experimental screening, with 84 subjects (1.3%) showing positive results for apoA2-ATQ/AT. Pancreatic abnormalities were recognized in 26 of the 84 subjects from imaging examinations. Pancreatic abnormalities detected included 1 PC and 15 HR abnormalities, such as cystic lesions including intraductal papillary mucinous neoplasm. The PPV of apoA2-ATQ/AT for detecting PC and HR was 33.3%. Moreover, a combination study with another cross-sectional study revealed that the area under the curve for apoA2-ATQ/AT to distinguish PC from healthy controls was 0.903. ApoA2-ATQ/AT has the potential to enrich PC and HR by increasing the diagnostic probability before imaging examinations.
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http://dx.doi.org/10.3390/cancers12092625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564617PMC
September 2020

A case of high-grade pancreatic intraepithelial neoplasia diagnosed based on focal pancreatic parenchymal atrophy after acute pancreatitis.

Clin J Gastroenterol 2020 Dec 17;13(6):1338-1342. Epub 2020 Aug 17.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

A 60-year-old male visited a previous hospital with upper abdominal pain. He was diagnosed with localized mild acute pancreatitis. Three months later, abdominal contrast-enhanced computed tomography showed focal parenchymal atrophy of the pancreas with distal pancreatic duct dilation. No obvious solid mass could be found at the site of the pancreatic duct stenosis on imaging examinations. Endoscopic retrograde pancreatography showed focal mild stenosis with distal pancreatic duct dilation in the tail of the pancreas. Carcinoma in situ of the pancreas was strongly suspected, especially based on the presence of focal atrophy of the pancreas around the site of stenosis of the main pancreatic duct and the distal pancreatic duct dilation. Laparoscopic distal pancreatectomy was performed. Histologically, high-grade pancreatic intraepithelial neoplasia was found in the epithelium of the stenotic main pancreatic duct and its branches. This case suggests that localized acute pancreatitis and focal atrophy of the pancreas with distal dilation of the pancreatic duct could be important clinical manifestations of pancreatic carcinoma in situ.
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http://dx.doi.org/10.1007/s12328-020-01208-2DOI Listing
December 2020

Prediction of pancreatic atrophy after steroid therapy using equilibrium-phase contrast computed tomography imaging in autoimmune pancreatitis.

JGH Open 2020 Aug 10;4(4):677-683. Epub 2020 Mar 10.

Division of Gastroenterology, Department of Internal Medicine Kobe University Graduate School of Medicine Kobe Japan.

Background And Aims: Imaging tools for predicting pancreatic atrophy after steroid therapy in autoimmune pancreatitis (AIP) have not been established. As delayed equilibrium-phase contrast enhancement in computed tomography (CE-CT) may reflect interstitial fibrosis, we evaluated the ability of equilibrium-phase CT imaging for predicting pancreatic atrophy.

Methods: Forty-six steroid-treated AIP patients who underwent contrast-enhanced CT at our university hospital were included in this retrospective study. CT attenuation (Hounsfield units [HU]) values in noncontrast images (NC) and equilibrium-phase images (EP) and the differences in HU values between NC and EP images (SUB) were measured. Pancreatic volume was measured in CE-CT before (Vol) and after (Vol) steroid therapy. The volume reduction rate was calculated. The relationships of CT values with pancreatic atrophy, Vol, volume reduction rate, and diabetes exacerbation were investigated.

Results: CT values in the EP and SUB images before steroid therapy were associated with pancreatic atrophy after steroid therapy (atrophy nonatrophy 114.5 ± 12.8 99.5 ± 11.1, = 0.0002; 70.9 ± 14.72 57.2 ± 13.1, = 0.003, respectively), but CT values in NC images were not ( = 0.42). CT values in EP and SUB images before steroid therapy were correlated with Vol (EP images = -0.70, = 0.002; SUB images = -0.68, = 0.03) and volume reduction rate after steroid therapy (EP images: = -0.55, < 0.0001; SUB images = -0.45, = 0.002). Diabetes exacerbation was associated with higher EP and SUB values ( = 0.009 and = 0.04, respectively).

Conclusion: Equilibrium-phase contrast CT imaging may facilitate prediction of pancreatic atrophy after steroid therapy in AIP.
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http://dx.doi.org/10.1002/jgh3.12316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411657PMC
August 2020

A Case in which an Intraductal Papillary Neoplasm of the Bile Duct Was Surgically Resected 12 Years after the Initial Diagnosis.

Intern Med 2020 Nov 21;59(22):2879-2883. Epub 2020 Jul 21.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.

A 66-year-old Japanese man was referred to our hospital with multiple giant liver cysts. The cysts had already been detected as multiple 3-cm cysts with small nodules at another hospital 12 years prior to this presentation. The cysts were diagnosed as an intraductal papillary neoplasms of the bile duct (IPNB) occupying the right lobe of the liver. Extended right lobectomy was performed. Based on the pathological findings, the tumor was diagnosed to be an oncocytic-type IPNB with minimal invasion. This experience suggests that the progression of IPNBs occur relatively slowly. The present case might provide important information for understanding the natural history of IPNBs.
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http://dx.doi.org/10.2169/internalmedicine.4891-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725632PMC
November 2020

Rb and p53 Execute Distinct Roles in the Development of Pancreatic Neuroendocrine Tumors.

Cancer Res 2020 09 26;80(17):3620-3630. Epub 2020 Jun 26.

Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Shogoin, Sakyo-ku, Kyoto, Japan.

Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1 to 3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the gene ( ) in mice did not affect pancreatic exocrine cells, the α-cell/β-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18-20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a mutation ( ) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a mutation with gene deletion ( ) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In mice, mRNA expression of and , negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating and genes, we established a multistep progression model from dysplastic islet to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET. SIGNIFICANCE: Pancreas-specific manipulation of and genes induced malignant transformation of islet cells, reproducing stepwise progression from microadenomas to indolent (grade 1) and subsequent aggressive PanNETs (grade 2-3).
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http://dx.doi.org/10.1158/0008-5472.CAN-19-2232DOI Listing
September 2020

A unique device enabling electrohydraulic lithotripsy with an ultraslim scope for difficult stones after endoscopic ultrasound-guided biliary drainage.

Endoscopy 2021 Feb 5;53(2):E52-E53. Epub 2020 Jun 5.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

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http://dx.doi.org/10.1055/a-1180-7820DOI Listing
February 2021

Troubleshooting for severe acute cholangitis caused by proximally migrated metal stent into the intrahepatic bile duct: Stent shortening via a balloon catheter.

Dig Endosc 2020 Jul 29;32(5):e112-e113. Epub 2020 May 29.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.

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http://dx.doi.org/10.1111/den.13711DOI Listing
July 2020

Endoscopic shielding technique using polyglycolic acid sheets with fibrin glue for perforation following endoscopic ampullectomy.

Dig Endosc 2020 Sep 23;32(6):992. Epub 2020 Jun 23.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.

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http://dx.doi.org/10.1111/den.13744DOI Listing
September 2020

Endoscopic Self-Expandable Metal Stent Placement for Malignant Afferent Loop Obstruction After Pancreaticoduodenectomy: A Case Series and Review.

Clin Endosc 2020 Jul 3;53(4):491-496. Epub 2020 Mar 3.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

In this study, we assessed a series of our cases in which endoscopic self-expandable metal stents (SEMSs) were used to treat malignant afferent loop obstruction (ALO) that arose after pancreaticoduodenectomy (PD). We retrospectively examined the records of 7 patients who underwent endoscopic SEMS placement for malignant ALO following PD. Clinical success was achieved in all cases. The median procedure time was 30 min (range, 15-50 min). There were no cases of stent occlusion, and no procedure-related adverse events were encountered. All patients died of their primary disease, and the median overall survival period was 155 days (range, 96-374 days). A re-intervention involving endoscopic ultrasound-guided hepaticogastrostomy combined with antegrade stenting was performed for obstructive jaundice and acute cholangitis in 1 case. In conclusion, endoscopic SEMS placement may be an effective and safe treatment for malignant ALO that arises after PD.
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http://dx.doi.org/10.5946/ce.2019.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403016PMC
July 2020

Shortening antibiotic duration in the treatment of acute cholangitis: rationale and study protocol for an open-label randomized controlled trial.

Trials 2020 Jan 17;21(1):97. Epub 2020 Jan 17.

Department of Gastroenterology, Kobe University Graduate School of Medicine, Kusunokicho 7-5-2, Chuoku, Kobe, Hyogo, 650-0017, Japan.

Background: Antimicrobial therapy with appropriate biliary drainage is considered the standard of care for acute cholangitis, but the optimal duration of antimicrobial therapy remains unknown. Seven to 10 days of antimicrobial therapy are common for the treatment of acute cholangitis, but a recent retrospective cohort study suggested a shorter duration might be effective. A shorter duration of antimicrobial therapy can be beneficial in decreasing the length of hospital stay, improving patients' quality of life, decreasing adverse effects, and even contributing to a decrease in the occurrence of antimicrobial resistance.

Methods/design: We will conduct a multi-centre, open-label, randomized, non-inferiority trial to compare short-course therapy (SCT) with conventional long-course therapy (LCT) in treating patients with acute cholangitis. SCT consists of 5-day intravenous antimicrobial therapy if the patients had clinical improvement, while at least 7 days of intravenous antibiotics will be provided to the LCT group. The primary outcome is clinical cure at 30 days after onset. Patients will be randomly assigned in an open-label fashion. A total sample size of 150 was estimated to provide a power of 80% with a one-sided α level of 2.5% and a non-inferiority margin of 10%.

Discussion: This trial is expected to reveal whether SCT is non-inferior to conventional LCT or not, and may provide evidence that one can shorten the treatment duration for acute cholangitis for the benefit of patients.

Trial Registration: University Hospital Medical Information Network, UMIN000028382. Registered on 30 August 2017.
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http://dx.doi.org/10.1186/s13063-020-4046-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969404PMC
January 2020

An autopsy case of granulocyte colony-stimulating factor-producing pancreatic adenosquamous carcinoma.

Clin J Gastroenterol 2020 Jun 16;13(3):448-454. Epub 2019 Nov 16.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

A 60-year-old female was admitted to hospital with a continuous fever, a decreased appetite, and abdominal pain. Laboratory tests showed an elevated peripheral leukocyte count (13,800/μl) and increased C-reactive protein (19.1 mg/dl) and carbohydrate antigen 19-9 (4057 U/ml) levels. Abdominal contrast-enhanced computed tomography showed multiple bulky hypovascular nodules in the liver, swelling of the paraaortic lymph nodes, and a hypovascular mass (diameter 3.0 cm) in the pancreatic body. The serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 were 172 pg/μl and 541 pg/µl, respectively. Liver biopsy specimens revealed an adenosquamous carcinoma, which was positively immunostained for G-CSF. We diagnosed the patient with G-CSF-producing pancreatic cancer with multiple metastases. Four courses of gemcitabine with dexamethasone and one course of nab-paclitaxel and gemcitabine were administered. Although the pancreatic tumor and paraaortic lymph node metastases decreased in size, the liver metastases continued to grow. The patient died 4 months after the diagnosis of pancreatic cancer. An autopsy resulted in the tumor being diagnosed as poorly differentiated adenosquamous pancreatic carcinoma, which was histopathologically G-CSF-positive. Although G-CSF-producing pancreatic adenosquamous carcinomas are extremely rare, they have been encountered more frequently in recent years. In such cases, chemotherapy combined with dexamethasone might be effective at temporarily improving the patient's condition.
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http://dx.doi.org/10.1007/s12328-019-01067-6DOI Listing
June 2020

Eosinophilic Cholangitis Without Biliary Stricture After the Treatment of Eosinophilic Esophagitis.

ACG Case Rep J 2019 Jun 26;6(6):e00099. Epub 2019 Jun 26.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Eosinophilic cholangitis (EC) is an uncommon, benign, self-limiting disease, which typically causes bile duct stricture with eosinophil infiltration. We report the case of a 70-year-old woman who presented with abdominal pain diagnosed with EC after treatment for eosinophilic esophagitis. All previous reported cases of EC had bile duct stricture seen on magnetic resonance cholangiopancreatography or cholangiogram during endoscopic retrograde cholangiopancreatography, but only wall thickness of the common bile duct was noted in our case. Although rare, EC should be considered when wall thickening of the bile duct is observed, even without stricture.
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http://dx.doi.org/10.14309/crj.0000000000000099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722338PMC
June 2019

Long-term outcomes of EUS-guided transluminal stent deployment for benign biliary disease: Multicenter clinical experience (with videos).

Endosc Ultrasound 2019 Nov-Dec;8(6):398-403

Therapeutic Endoscopic Ultrasound Group: TEUS; Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.

Background And Objectives: Biliary drainage (BD) under EUS guidance is usually indicated for malignant biliary obstruction. Recently, EUS-guided transluminal treatment has been applied to benign biliary disease (BBD). This multicenter retrospective study evaluated the clinical impact of EUS-guided transluminal stent deployment for BBD with long-term follow-up.

Patients And Methods: This retrospective study investigated patients treated between September 2015 and October 2016 at participating hospitals in the therapeutic endoscopic group. The inclusion criteria comprised complications with BBD obstructive jaundice or cholangitis and failed endoscopic retrograde cholangiopancreatography or inaccessible ampulla of Vater.

Results: Twenty-six patients underwent EUS-guided transluminal stent deployment. Indications for EUS-guided transluminal stent deployment comprised anastomotic biliary stricture (n = 17), bile duct stones (n = 5), inflammatory biliary stricture (n = 3), and acute pancreatitis prevention (n = 1). Thirteen of these 26 patients underwent scheduled reintervention, with technical success achieved in all 13 patients. None of the deployed stents became dysfunctional. Among the 13 patients who underwent reintervention on demand, stents had become dysfunctional in six patients (stent patency: 48, 90, 172, 288, 289, and 608 days). Reintervention was successfully performed in all patients. During follow-up (median, 749 days), severe adverse events were not seen in any patients.

Conclusion: We concluded that EUS-guided transluminal stent deployment for BBD is feasible and safe. Because metal stent dysfunction was more frequent when deployed on demand, such stents should be exchanged for plastic stents in a scheduled manner if a metal stent is used.
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http://dx.doi.org/10.4103/eus.eus_45_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927148PMC
September 2019

Type 1 Autoimmune Pancreatitis with Imaging Appearance Similar to That of Malignant Cystic Tumor.

Case Rep Gastroenterol 2019 May-Aug;13(2):265-270. Epub 2019 Jun 14.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

A 79-year-old man was admitted with asymptomatic elevation of liver enzymes and tumor markers. Abdominal contrast-enhanced computed tomography demonstrated swelling of the pancreatic head, and additional blood test showed raised IgG4 levels. Histological examination by endoscopic ultrasonography (EUS)-guided fine needle aspiration for pancreatic head mass revealed storiform fibrosis and IgG4-positive plasma cell infiltration. We diagnosed this case as type 1 autoimmune pancreatitis (AIP). In addition, there was a cystic lesion in the pancreatic body apart from the pancreatic head mass. A mural nodule in the multilocular cyst was detected by EUS, and there was positive uptake of fluorodeoxyglucose in positron emission tomography/magnetic resonance imaging. The preoperative diagnosis of this cystic lesion was intraductal papillary mucinous carcinoma, and distal pancreatomy was performed. Histopathological findings showed various sizes of retention cysts caused by IgG4-positive plasma cell infiltration around the pancreatic branch ducts. The mural nodule was a fibrotic mass with diffuse infiltration of IgG4-positive cells. This cystic lesion mimicking malignant cystic neoplasm occurred in relation to AIP. This case provided important information helping to understand the mechanism of formation of mural nodules in multilocular cysts in patients with type 1 AIP.
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http://dx.doi.org/10.1159/000500477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600027PMC
June 2019

A rescue approach using a neo papilla for choledocholithiasis in patient with benign duodenal stricture.

Endoscopy 2019 11 4;51(11):E327-E328. Epub 2019 Jun 4.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

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http://dx.doi.org/10.1055/a-0919-4215DOI Listing
November 2019

Endoscopic ultrasound-guided gastrojejunostomy using fully covered metal stent combined with large-loop double-pigtail stent for malignant afferent loop syndrome.

Endoscopy 2019 10 23;51(10):E303-E304. Epub 2019 May 23.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

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http://dx.doi.org/10.1055/a-0916-8532DOI Listing
October 2019

Significance of pancreatic calcification on preoperative computed tomography of intraductal papillary mucinous neoplasms.

J Gastroenterol Hepatol 2019 Sep 18;34(9):1648-1655. Epub 2019 Jun 18.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

Background And Aim: Chronic pancreatitis is a risk factor for pancreatic cancer. Pancreatic calcification is a characteristic of chronic pancreatitis; however, its significance for intraductal papillary mucinous neoplasm (IPMN) oncogenesis remains unknown. Therefore, we investigated the relationship between pancreatic calcification and invasive IPMN.

Methods: This study included 157 patients who underwent resection for IPMN between April 2001 and October 2016 (intraductal papillary mucinous adenoma, n = 76; noninvasive intraductal papillary mucinous carcinoma [IPMC], n = 32; and invasive IPMC, n = 49). We divided the subjects on the basis of the presence/absence of pancreatic calcification on preoperative computed tomography (CT). The factors associated with pancreatic calcification were investigated in univariate analyses. Then, multivariate logistic regression analyses of the relationship between pancreatic calcification and invasive IPMC (after adjusting for clinical or imaging characteristics) were conducted.

Results: Preoperative CT revealed pancreatic calcification in 17.2% (27/157) of the resected IPMN. In the univariate analyses, jaundice, high serum carbohydrate antigen 19-9 levels, and invasive IPMC were significantly associated with pancreatic calcification (4/27 [14.8%] vs 4/130 [3.1%], 0.01; 12/27 [44.4%] vs 31/130 [23.8%], 0.03; and 15/27 [55.6%] vs 34/130 [26.2%], 0.001, respectively). Pancreatic calcification was significantly associated with invasive IPMC (multivariate odds ratio = 2.88, 95% confidence interval [95% CI] = 1.15-7.21, 0.03, adjusted for clinical characteristics; odds ratio = 5.50, 95% CI = 1.98-15.3, 0.001, adjusted for imaging characteristics).

Conclusions: Pancreatic calcification on CT is associated with invasive IPMC. Pancreatic calcification might be a predictor of invasive IPMC.
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http://dx.doi.org/10.1111/jgh.14732DOI Listing
September 2019

Clinical outcomes of ampullary neoplasms in resected margin positive or uncertain cases after endoscopic papillectomy.

World J Gastroenterol 2019 Mar;25(11):1387-1397

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.

Background: Endoscopic papillectomy (EP) for benign ampullary neoplasms could be a less-invasive alternative to pancreatoduodenectomy (PD). There are some problems and limitations with EP. The post-EP resection margins of ampullary tumors are often positive or uncertain because of the burning effect of EP. The clinical outcomes of resected margin positive or uncertain cases after EP remain unknown.

Aim: To investigate the clinical outcomes of resected margin positive or uncertain cases after EP.

Methods: Between January 2007 and October 2018, all patients with ampullary tumors who underwent EP at Kobe University Hospital were included in this study. The indications for EP were as follows: adenoma, as determined by preoperative endoscopic biopsy, without bile/pancreatic duct extension, according to endoscopic ultrasound or intraductal ultrasound. The clinical outcomes of resected margin positive or uncertain cases after EP were retrospectively investigated.

Results: Of the 45 patients, 29 were male, and 16 were female. The mean age of the patients was 65 years old. Forty-one patients (89.5%) underwent resection, and 4 patients (10.5%) underwent piecemeal resection. After EP, 33 tumors were histopathologically diagnosed as adenoma, and 12 were diagnosed as adenocarcinoma. The resected margins were positive or uncertain in 24 patients (53.3%). Of these cases, 15 and 9 were diagnosed as adenoma and adenocarcinoma, respectively. Follow-up observation was selected for all adenomas and 5 adenocarcinomas. In the remaining 4 adenocarcinoma cases, additional PD was performed. Additional PD was performed in 4 cases, and residual carcinoma was found after the additional PD in 1 of these cases. In the follow-up period, local tumor recurrence was detected in 3 cases. Two of these cases involved primary EP-diagnosed adenoma. The recurrent tumors were also adenomas detected by biopsy. The remaining case involved primary EP-diagnosed adenocarcinoma. The recurrent tumor was also an adenocarcinoma. All of the recurrent tumors were successfully treated with argon plasma coagulation (APC). There was no local or lymph node recurrence after the APC. The post-APC follow-up periods lasted for 57.1 to 133.8 mo. No ampullary tumor-related deaths occurred in all patients.

Conclusion: Resected margin positive or uncertain cases after EP could be managed by endoscopic treatment including APC, even in cases of adenocarcinoma. EP could become an effective less-invasive first-line treatment for early stage ampullary tumors.
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http://dx.doi.org/10.3748/wjg.v25.i11.1387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429348PMC
March 2019
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