Publications by authors named "Shinjiro Kobayashi"

77 Publications

The Influence of Pre-Procedural Imaging and Cystic Duct Cholangiography on Endoscopic Transpapillary Gallbladder Drainage in Acute Cholecystitis.

Diagnostics (Basel) 2021 Jul 16;11(7). Epub 2021 Jul 16.

Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki 216-8511, Kanagawa, Japan.

Endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis is challenging. We evaluated the influence of pre-procedural imaging and cystic duct cholangiography on ETGBD. Patients who underwent ETGBD for acute cholecystitis were retrospectively examined. The rate of gallbladder contrast on cholangiography, the accuracy of cystic duct direction and location by computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP), and the relationship between pre-procedural imaging and the technical success of ETGBD were investigated. A total of 145 patients were enrolled in this study. Gallbladder contrast on cholangiography was observed in 29 patients. The accuracy of cystic duct direction and location (proximal or distal, right or left, and cranial or caudal) by CT were, respectively, 79%, 60%, and 58% by CT and 68%, 55%, and 58% by MRCP. Patients showing gallbladder contrast on cholangiography underwent ETGBD with a significantly shorter procedure time and a lower rate of cystic duct injury. No other factors affecting procedure time, technical success, and cystic duct injury were identified. Pre-procedural evaluation of cystic duct direction and location by CT or MRCP was difficult in patients with acute cholecystitis. Patients who showed gallbladder contrast on cholangiography showed a shorter procedure time and a lower rate of cystic duct injury.
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http://dx.doi.org/10.3390/diagnostics11071286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307666PMC
July 2021

Efficacy of endoscopic large balloon dilation extended for 2 minutes in bile duct stone removal: A multicenter retrospective study.

J Hepatobiliary Pancreat Sci 2021 Jul 30. Epub 2021 Jul 30.

Department of Gastroenterology and Hepatology, School of Medicine, St. Marianna University, Kawasaki, Japan.

Background/purpose: There is no evidence regarding the optimal balloon dilation time during endoscopic papillary large balloon dilation (EPLBD). The study aim was to evaluate the efficacy of 2-minute extended balloon dilation for EPLBD.

Methods: Two hundred and five patients who underwent EPLBD during endoscopic retrograde cholangiopancreatography (ERCP) for bile duct stones at three tertiary centers were included in the analysis. Clinical outcomes and the adverse events were compared between the 0-minute group (n = 94, balloon deflated immediately after waist disappearance) and the 2-minute group (n = 111, balloon dilation maintained for 2 minutes after waist disappearance). The risk factors of post-ERCP pancreatitis (PEP) after EPLBD were assessed.

Results: There were no significant differences in the stone removal rates and hospitalization periods between the two groups. However, the total ERCP procedure time was significantly shorter in the 2-minute group (40.6 vs 48.9 min, P = .03). The incidence of PEP was 7.4% in the 0-minute group and significantly lower at 0.9% in the 2-minute group (P = .04). Multivariate analysis identified without 2-minute extended EPLBD as a significant risk factor of PEP (OR: 9.9, P = .045).

Conclusions: Extension of EPLBD for 2 minutes helped prevent PEP and shortened the procedure time.
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http://dx.doi.org/10.1002/jhbp.1029DOI Listing
July 2021

Incidence and management of cystic duct perforation during endoscopic transpapillary gallbladder drainage for acute cholecystitis.

Dig Endosc 2021 Feb 18. Epub 2021 Feb 18.

Departments of, Department of, Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kanagawa, Japan.

Background And Aim: Evidence regarding the incidence and clinical outcome of cystic duct perforation (CDP) during endoscopic transpapillary gallbladder drainage (ETGBD) is inadequate. The present study aimed to evaluate the incidence and management of CDP during ETGBD.

Methods: Between March 2011 and December 2019, 249 patients underwent initial ETGBD for acute cholecystitis. The incidence of CDP was retrospectively examined and the outcomes between the CDP and non-CDP groups were compared.

Results: CDP during ETGBD occurred in 23 (9.2%) of 249 patients (caused by guidewire in 15 and cannula in 8). ETGBD was successful in 10 patients following CDP. In 13 patients who failed ETGBD, 11 underwent bile duct drainage during the same session; nine patients underwent gallbladder decompression by other methods, such as percutaneous drainage. Clinical resolution for acute cholecystitis was achieved in 20 patients, and no bile peritonitis was noted. ETGBD technical success rates (45.3% vs. 91.2%, p < 0.001), ETGBD procedure times (66.5 vs. 54.8 min, p = 0.041), and hospitalization periods (24.5 vs. 18.7 days, p = 0.028) were significantly inferior in the CDP group (n = 23) compared with the non-CDP group (n = 216). There were no differences in clinical success and adverse events other than CDP between both groups.

Conclusions: Cystic duct perforation reduced the ETGBD technical success rate. However, even in patients with cystic duct perforation, an improvement of acute cholecystitis was achieved by subsequent successful ETGBD or additional procedures, such as percutaneous drainage.
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http://dx.doi.org/10.1111/den.13959DOI Listing
February 2021

Novel Modified Blumgart Technique to Reduce Postoperative Pancreatic Fistula After Pancreaticojejunostomy-Compressed Pancreatic Stump (COMPAS) Anastomosis.

J Gastrointest Surg 2021 04;25(4):1082-1086

Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.

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http://dx.doi.org/10.1007/s11605-020-04848-4DOI Listing
April 2021

Current status and management of pancreatic trauma with main pancreatic duct injury: A multicenter nationwide survey in Japan.

J Hepatobiliary Pancreat Sci 2021 Feb 19;28(2):183-191. Epub 2021 Jan 19.

Department of Gastroenterological Surgery, Kagawa University, Kita-gun, Japan.

Background: Pancreatic trauma is reportedly associated with high morbidity and mortality. Main pancreatic duct (MPD) injury is critical for treatment.

Methods: As a study project of the Japanese Society for Abdominal Emergency Medicine (JSAEM), we collected the data of 163 patients with pancreatic trauma who were diagnosed and treated at JSAEM board-certified hospitals from 2006 to 2016. Clinical backgrounds, diagnostic approaches, management strategies, and outcomes were evaluated.

Results: Sixty-four patients (39%) were diagnosed as having pancreatic trauma with MPD injury that resulted in 3% mortality. Blunt trauma and isolated pancreatic injury were independent factors predicting MPD injury. Nine of 11 patients with MPD injury who were initially treated nonoperatively had serious clinical sequelae and five (45%) required surgery as a secondary treatment. Among all cases, the detectability of MPD injury of endoscopic retrograde pancreatography (ERP) was superior to that of other imaging modalities (CT or MRI), with higher sensitivity and specificity (sensitivity = 0.96; specificity = 1.0).

Conclusions: Acceptable outcomes were observed in pancreatic trauma patients with MPD injury. Nonoperative management should be carefully selected for MPD injury. ERP is recommended to be performed in patients with suspected MPD injury and stable hemodynamics.
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http://dx.doi.org/10.1002/jhbp.877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986433PMC
February 2021

Complete Lymphadenectomy Around the Entire Superior Mesenteric Artery Improves Survival in Artery-First Approach Pancreatoduodenectomy for T3 Pancreatic Ductal Adenocarcinoma.

World J Surg 2021 Mar 10;45(3):857-864. Epub 2020 Nov 10.

Department of Gastroenterology and Hepatology, School of Medicine, St. Marianna University, Kawasaki, Japan.

Background: Artery-first approach pancreatoduodenectomy (AFA-PD) is an important technique for treating pancreatic ductal adenocarcinoma (PDAC). However, it remains unknown whether performing complete lymphadenectomy around the entire superior mesenteric artery (SMA) is associated with better outcomes. In this retrospective study, we aimed to investigate whether this approach improved overall and recurrence-free survival in patients with PDAC.

Methods: We identified 88 patients with T3 PDAC who underwent PD at St. Marianna University School of Medicine, Kawasaki, Japan, between April 2005 and October 2017. Two groups were defined: an "AFA-PD group" (n = 45) who had undergone AFA-PD in addition to complete lymphadenectomy around the entire SMA, and a "conventional PD group" (n = 43) in whom complete lymphadenectomy had not been performed (conventional group). Univariate and multivariate survival analyses were performed to identify risk factors for overall and disease-free survival.

Results: The AFA-PD group had a longer median survival time (40.3 vs. 22.6 months; p = 0.0140) and a higher 5-year survival rate (40.3% vs. 5.9%, p = 0.005) than the conventional PD group. Multivariate analysis showed that AFA-PD with complete lymphadenectomy around the entire SMA was an independent factor for improved overall survival (p = 0.022). Recurrences around the SMA were significantly less frequent in the AFA-PD group than in the conventional group (22.2% vs. 44.2%, p = 0.041).

Conclusions: AFA-PD with complete lymphadenectomy around the entire SMA can prevent recurrences around the SMA and may prolong overall survival in patients with PDAC.
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http://dx.doi.org/10.1007/s00268-020-05856-wDOI Listing
March 2021

Risk factors for pancreatic fistula grade C after pancreatoduodenectomy: A large prospective, multicenter Japan-Taiwan collaboration study.

J Hepatobiliary Pancreat Sci 2020 Sep 6;27(9):622-631. Epub 2020 Aug 6.

Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.

Background/purpose: Grade C postoperative pancreatic fistula (POPF), as defined by International Study Group of Pancreatic Fistula (ISGPF), is the most life-threatening complication after pancreatoduodenectomy (PD). This study aims to evaluate risk factors for Grade C POPF after PD.

Methods: This is a prospective, multicenter study based in Japan and Taiwan. Between December 2014 and May 2017, 3022 patients were enrolled in this study and 2762 patients were analyzed. We analyzed risk factors of Grade C POPF based on the updated 2016 ISGPF scheme (organ failure, reoperation, and/or death).

Results: Among 2762 patients, 46 patients (1.7%) developed Grade C POPF after PD. The mortality rate of the 46 patients with Grade C POPF was 37.0%. On the multivariate analysis, six independent risk factors for Grade C POPF were found; BMI ≥ 25.0 kg/m , chronic steroid use, preoperative serum albumin <3.0 mg/dL, soft pancreas, operative time ≥480 minutes, and intraoperative transfusion. The c-statistic of our risk scoring model for Grade C POPF using these risk factors was 0.77. The score was significantly higher in Grade C POPF than in Grade B POPF (P < .001) or none/biochemical leak (P < .001).

Conclusions: This prospective study showed risk factors for Grade C POPF after PD.
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http://dx.doi.org/10.1002/jhbp.799DOI Listing
September 2020

Use of washing cytology from removed self-expandable metal stents for biliary strictures: a novel cytology method.

Endosc Int Open 2020 Jun 25;8(6):E748-E752. Epub 2020 May 25.

Department of Gastroenterology and Hepatology, St. Marianna University, School of Medicine, Kawasaki, Japan.

Removability is one of the important features of biliary covered self-expandable metal stents (CSEMS). In this study, we evaluated the diagnostic ability of washing cytology of removed CSEMS. For 14 removed CSEMS that had been placed for the biliary strictures (12 malignant, 2 benign), the surface of CSEMS was washed with saline, and pathological examination of the washing liquid as cytology (CSEMS washing cytology) was performed. The specimen sampling rates and sensitivity for malignancy of CSEMS washing cytology were 92.9 % and 41.7 %, respectively. Sensitivity according to the primary disease was 60.0 % for bile duct cancer and 20 % for pancreatic cancer. Sensitivities based on the methods of stent removal were 16.7 % and 66.7 % for removal through the channel of the scope and with the scope, respectively. Therefore, it is possible that sensitivity of CSEMS washing cytology is higher in bile duct cancer and for removal with the scope. In conclusion, CSEMS washing cytology may have potential as a pathological diagnostic method.
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http://dx.doi.org/10.1055/a-1144-2668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247891PMC
June 2020

Endoscopic Transpapillary Gallbladder Drainage for Acute Cholecystitis After Biliary Self-Expandable Metal Stent Placement.

Surg Laparosc Endosc Percutan Tech 2020 Oct;30(5):416-423

Departments of Gastroenterology and Hepatology.

Background: Endoscopic transpapillary gallbladder drainage (ETGBD) for acute cholecystitis (AC) after self-expandable metal stent (SEMS) placement is technically challenging and there are no reports about its outcome in a several cases. This study aims to assess the outcomes of ETGBD for AC after SEMS placement.

Methods: Between April 2011 and April 2019, 314 patients underwent SEMS placement for biliary stricture. Among them, 12 of 21 patients who developed AC after SEMS placement underwent ETGBD. In general, ETGBD was performed after SEMS removal in cases in which a covered SEMS was previously placed or with the SEMS kept in place in cases in which an uncovered SEMS was previously placed. When the orifice of the cystic duct overlapped the uncovered SEMS, ETGBD was performed through the mesh of the SEMS.

Results: Among the 12 patients who underwent ETGBD, the previously placed SEMS was in the distal (n=8) or perihilar (n=4) bile duct. The type of SEMS placed in the distal bile duct was covered in 7 (fully covered: 6, partially covered: 1) and uncovered in 1, whereas that in the perihilar bile duct was uncovered for all. The technical success rate of ETGBD was 83.3% (10/12), and that according to the previous SEMS placement site was 75.0% (6/8) for the distal bile duct and 100% (4/4) for the perihilar bile duct. In the technically successful, the clinical success rate for AC was 90.0% (9/10). The rate of adverse event was 16.7% (2/12) (stent kink: 1, tube self-removal: 1).

Conclusions: ETGBD can have relatively good outcomes for AC after SEMS placement.
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http://dx.doi.org/10.1097/SLE.0000000000000802DOI Listing
October 2020

Endoscopic transpapillary gallbladder drainage using the balloon occlusion method to advance the guidewire into the cystic duct.

Endoscopy 2020 09 18;52(9):E339-E341. Epub 2020 Mar 18.

Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan.

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http://dx.doi.org/10.1055/a-1125-5826DOI Listing
September 2020

Significance of a preoperative tumor marker gradient for predicting microvascular invasion in cases of hepatocellular carcinoma.

Mol Clin Oncol 2020 Mar 10;12(3):290-294. Epub 2020 Jan 10.

Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan.

Although vascular invasion is an important factor in the progression and treatment of hepatocellular carcinoma (HCC), it remains difficult to determine, on the basis of preoperative imaging alone, whether vascular invasion, especially microvascular invasion, has occurred. The current retrospective study enrolled 292 patients who, between 2004 and 2014, underwent curative hepatectomy as an initial treatment for HCC. The patients were divided between those with (n=70) and those without (n=222) microvascular invasion. Whether tumor-marker-based prediction of microvascular invasion was possible was assessed by comparing the preoperative serum α-fetoprotein (AFP) and prothrombin induced by vitamin K absence or antagonist-II concentrations between two groups of patients. The AFP concentration was significantly higher in patients with microvascular invasion compared with patients without microvascular invasion (P=0.0019). Stepwise logistic regression analysis demonstrated the AFP concentration and the logarithmic conversion ratio of the AFP gradient (log AFP grad) to be useful (P=0.0019; 0.0424) for predicting microvascular invasion. The serum AFP concentration and log AFP grad appear to be clinically useful in predicting microvascular invasion in patients with HCC.
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http://dx.doi.org/10.3892/mco.2020.1975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016610PMC
March 2020

Tetrandrine Increases the Sensitivity of Human Lung Adenocarcinoma PC14 Cells to Gefitinib by Lysosomal Inhibition.

Anticancer Res 2019 Dec;39(12):6585-6593

Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan

Background/aim: Human lung adenocarcinoma PC14 cells without mutations in the epidermal growth factor receptor (EGFR) are less sensitive to gefitinib than PC9 cells with EGFR mutations. We report the involvement of tetrandrine in autophagy flux as a mechanism that enhances the sensitivity of PC14 cells to gefitinib.

Materials And Methods: Sensitivity to gefitinib was determined by a growth inhibition assay, and quantitative real-time PCR, western blotting, and fluorescent immunostaining were used to detect autophagy.

Results: In PC14 cells, combined treatment with gefitinib and tetrandrine caused a significant increase in gefitinib sensitivity and autophagy-related mRNAs and proteins (LC3, etc.), and the LC3 protein accumulated in lysosomes. Furthermore, an autophagy flux assay revealed that tetrandrine inhibited lysosomes and that gefitinib promoted autophagy. Finally, the sensitivity of PC14 cells to gefitinib was enhanced with chloroquine.

Conclusion: Tetrandrine possibly increases the susceptibility of PC14 cells to gefitinib by lysosomal inhibition.
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http://dx.doi.org/10.21873/anticanres.13874DOI Listing
December 2019

Endoscopic Sphincterotomy before Fully Covered Metal Stent Placement Is Not Required for Distal Malignant Biliary Stricture due to a Pancreatic Head Tumor.

Gastroenterol Res Pract 2019 15;2019:9675347. Epub 2019 Jan 15.

Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan.

Background/aims: Endoscopic sphincterotomy (EST) is often performed before fully covered self-expandable metal stent (FCSEMS) placement in order to prevent pancreatitis. However, it is not clear whether EST prevents pancreatitis or affects other adverse events (AEs). This study is conducted to evaluate the necessity of EST before FCSEMS placement for distal malignant biliary strictures due to a pancreatic head tumor.

Methods: This study included 68 patients who underwent FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor. Treatment outcomes and AEs were retrospectively compared between 32 patients with EST before FCSEMS placement (EST group) and 36 patients without EST (non-EST group).

Results: The success rates of drainage for the EST and non-EST groups were 100% and 97.2%, respectively ( = 0.95). The incidence of pancreatitis in the EST and non-EST groups was 3.1% and 0%, respectively ( = 0.95). The incidence of hyperamylasemia in the EST and non-EST groups was 12.5% and 13.9%, respectively ( = 0.85). The incidence of all AEs in the EST and non-EST groups was 15.6% (pancreatitis: 1, cholecystitis: 2, and stent migration: 2) and 13.9% (cholecystitis: 3, stent migration: 2), respectively ( = 0.89).

Conclusions: EST before FCSEMS placement for distal malignant biliary stricture due to a pancreatic head tumor does not affect the successful drainage and incidence of adverse events. The necessity of EST to prevent pancreatitis before FCSEMS placement was deemed low.
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http://dx.doi.org/10.1155/2019/9675347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350600PMC
January 2019

Efficacy and Safety of Single-Session Endoscopic Stone Removal for Acute Cholangitis Associated with Choledocholithiasis.

Can J Gastroenterol Hepatol 2018 8;2018:3145107. Epub 2018 Aug 8.

Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan.

Background/aims: In early endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis due to choledocholithiasis, it is unclear that single-session stone removal can be safely performed. We examined the efficacy and safety of early single-session stone removal for mild-to-moderate acute cholangitis associated with choledocholithiasis.

Methods: Among patients with mild-to-moderate acute cholangitis associated with choledocholithiasis who underwent early ERCP (n = 167), we retrospectively compared the removal group (patients who underwent single-session stone removal; n = 78) with the drainage group (patients who underwent biliary drainage alone; n = 89) and examined the effectiveness and safety of single-session stone removal by early ERCP.

Results: The patients in the removal group had significantly fewer and smaller stones compared with those in the drainage group. The single-session complete stone removal rate was 85.9% in the removal group. The complication rate in early ERCP was 11.5% in the removal group and 10.1% in the drainage group, with no significant difference (P = 0.963). On comparing patients who underwent early endoscopic sphincterotomy (EST) with those who underwent elective EST after cholangitis had improved, the post-EST bleeding rates were 6.8% and 2.7%, respectively, with no significant difference (P = 0.600). The mean duration of hospitalization was 11.9 days for the removal group and 19.9 days for the drainage group, indicating a shorter stay for the removal group (P < 0.001). In multiple linear regression analysis, stone removal in early ERCP, number of stones, and C-reactive protein level were significant predictors of hospitalization period.

Conclusions: Single-session stone removal for mild-to-moderate acute cholangitis can be safely performed. It is useful from the perspective of shorter hospital stay.
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http://dx.doi.org/10.1155/2018/3145107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106953PMC
February 2019

Diagnostic Ability of Endoscopic Bile Cytology Using a Newly Designed Biliary Scraper for Biliary Strictures.

Dig Dis Sci 2019 01 23;64(1):241-248. Epub 2018 Jul 23.

Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, 216-8511, Japan.

Background: A new device with metallic wires for scrape cytology was developed.

Aims: To compare the diagnostic performance of scrape cytology and conventional cytology during endoscopic retrograde cholangiopancreatography for biliary strictures.

Methods: A total of 420 cases with biliary stricture underwent transpapillary bile cytology. Among them, there are 79 cases with scrape cytology using the new device (scrape group) and 341 cases with conventional cytology (control group). Seventy-two and 174 cases underwent biliary biopsy at the same time as bile cytology in the scrape and control group, respectively.

Results: The sensitivity for malignancy of bile cytology in the scrape and control group was 41.2% [pancreatic cancer (PC): 23.1%, biliary cancer (BC): 52.5%] and 27.1% (PC: 16.3%, BC: 38.0%), respectively (P = 0.023). When analyzed PC and BC, respectively, there was no significant difference between the two groups. In the both groups, the sensitivity was significantly higher for BC than PC. In the scrape group, there was no difference in the sensitivity between cytology and biopsy [39.7% (PC: 17.4%, BC: 55.3%)], but in the control group, a significantly lower sensitivity was observed with cytology than biopsy (36.4% (PC: 19.7%, BC: 50.0%)) (P = 0.046). When analyzed PC and BC, respectively, there was no significant difference between cytology and biopsy. The sensitivity of combined cytology and biopsy was 55.6% (PC: 30.4%, BC: 71.1%) in the scrape group and 47.0% (PC: 24.6%, BC: 64.3%) in the control group.

Conclusion: Scrape bile cytology for biliary strictures may be superior to conventional cytology.
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http://dx.doi.org/10.1007/s10620-018-5217-yDOI Listing
January 2019

[A Case in Which S-1 plus CDDP and S-1 Therapy Responded to Liver Metastasis Recurrence after Gastric Cancer Operation].

Gan To Kagaku Ryoho 2018 Apr;45(4):658-660

Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine.

A 55-year-old man underwent distal gastrectomy and D2 lymph node dissection for type 2 gastric cancer of the antrum. One year later, CEA elevation was discovered, and contrast-enhanced abdominal computed tomography(CT)revealed a 40 mm mass in the liver(S8), which was judged to be a metastatic recurrence of the gastric cancer.S -1 plus CDDP was administered in 5 courses, followed by regular treatment with S-1 alone.Two years after the recurrence was diagnosed, the patient's CEA level was found to be normal, and CT revealed almost total scarring.After 2 more years, there was still no sign of recurrence, so, with the patient's consent, we discontinued the chemotherapy.Eight years after the gastrectomy, a 10mm nodular shadow was observed in the left lower lung lobe, and resection was performed.Despite the earlier diagnosis of gastric adenocarcinoma, this mass was considered a primary lung adenocarcinoma, and the patient died of small-cell lung cancer 11 years and 8 months after the gastrectomy.It is notable that the liver metastasis in this case responded to the S-1 plus CDDP and S-1 therapies, and this response is considered in light of the literature.
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April 2018

[Pharmacological Mechanisms of Boiogito and Bofutsushosan in Diabetes and Obesity Models].

Yakugaku Zasshi 2018 ;138(3):389-403

Faculty of Pharmaceutical Sciences, Hokuriku University.

 The antihyperglycemic activities of extracts of boiogito (BOT) and bofutsushosan (BTS) were investigated in streptozotocin-induced (STZ)-diabetic mice. BOT extract containing Stephania tetrandra S. MOORE root (stephania), has more potent antihyperglycemic activity than BOT extract containing sinomenium stem (sinomenium). Extracts of stephania and astragalus root (astragalus) exert combined effects in the antihyperglycemic and insulinotropic activities of BOT extract. Fangchinoline, but not tetrandrine, in stephania plays a role in its activity. Formononetin in astragalus potentiates the actions of fangchinoline. Tetrandrine has antiangiogenic effects on choroidal vessels in STZ-diabetic rats, which are associated with the inhibition of tumor necrosis factor (TNF)-α-induced nuclear factor (NF)-κB activation. BTS extract has shown antihyperglycemic and insulinotropic activities whereas gardenia fruit (gardenia) extract in BTS has antihyperglycemic, but not insulinotropic, activity in the diabetic mice. Gardenia extract decreased the HOMA-IR level and increased insulin-stimulated 2-deoxyglucose (2-DG) uptake to skeletal muscle. The effects of gardenia extract on 2-DG uptake were associated with the upregulation of glucose transporter type 4 and Akt phosphorylation. Gardenia extract was also shown to have antihyperglycemic and insulinotropic actions in high-fat diet (HFD)-fed and STZ-diabetic mice. In addition, gardenia extract decreased the production of TNF-α and leptin, and increased the production of adiponectin in the visceral adipose tissues. In the early administration period, BTS extract increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues in HFD-fed obese mice. With a longer duration of administration, BTS extract improved insulin resistance and subsequently reduced serum leptin and triglyceride levels in parallel with visceral adipose tissue volume and size.
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http://dx.doi.org/10.1248/yakushi.17-00168DOI Listing
March 2018

Risk factors for failure of early recovery from pancreatoduodenectomy despite the use of enhanced recovery after surgery protocols and a physical aging score to predict postoperative risks.

J Hepatobiliary Pancreat Sci 2018 Apr 11;25(4):231-239. Epub 2018 Mar 11.

Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.

Background: Enhanced recovery after surgery (ERAS) protocols are beneficial for pancreatoduodenectomy (PD). Our aim was to evaluate risk factors associated with ERAS protocol failure after PD.

Methods: Clinical variables of 187 patients managed using ERAS protocols between April 2011 and April 2017, including non-early recovery (non-ER) patients, with complications or requiring a hospital stay ≥15 days, and early recovery (ER) patients, were compared. A physical aging (PA) score was devised to predict postoperative risks.

Results: Independent risk factors of complications were a pre-albumin level ≤18 mg/dl (odds ratio (OR) 2.197; 95% confidence interval (CI) 1.052-4.622), and an American Society of Anesthesiologists (ASA) score ≥II (OR 2.195; 95% CI 1.052-4.746). Independent risk factors for hospital stay ≥15 days (P < 0.001) were age ≥70 years (OR 2.438; 95% CI 1.122-5.299) and an ASA score ≥II (OR 2.348; 95% CI 1.109-4.968). The PA score included age, ASA score, and pre-albumin level. The complication rate for each PA score was as follows: score "0", 12.1%; score "1", 18.2%; score "2", 26.9%; score "3", 30.8%; and score "≥4", 47.2%.

Conclusions: Advanced age, poor nutrition, and serious illnesses can cause ERAS protocol failure. The PA score is effective for predicting postoperative progress.
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http://dx.doi.org/10.1002/jhbp.540DOI Listing
April 2018

The Vertical Array Reconstruction Technique in Pylorus-Preserving Pancreatoduodenectomy.

Dig Surg 2018 9;35(5):469-473. Epub 2018 Jan 9.

Department of Gastroenterological and General Surgery, St. Marianna University School of Medicine, Kawasaki, Japan.

Background/aims: We describe a new reconstruction method of duodenojejunal anastomosis, the "vertical array reconstruction" (VAR) technique, following pylorus-preserving pancreatoduodenectomy (PPPD).

Methods: The VAR technique aligns the stomach, duodenum, and jejunal loop vertically along the body's longitudinal axis. It was performed in 120 consecutive patients (between June 2008 and October 2015) who underwent PPPD. We evaluated the incidence of delayed gastric emptying (DGE).

Results: The incidence of DGE was 1.7% (n = 2). The proposed clinical grading classified these 2 cases of DGE as grade B. There was no DGE related to pancreatic fistula. The median duration to starting a solid diet was 3 days (range 3-5 days). The median operative time was 450 min (range 391-550 min).

Conclusion: The VAR technique allows the upper digestive tract to be aligned linearly and can minimize the risk of DGE after PPPD.
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http://dx.doi.org/10.1159/000485847DOI Listing
December 2018

Evaluation of CYP2D6 Protein Expression and Activity in the Small Intestine to Determine Its Metabolic Capability in the Japanese Population.

Biol Pharm Bull 2017 Sep 14;40(9):1344-1351. Epub 2017 Jun 14.

Department of Pharmacology, St. Marianna University School of Medicine.

CYP2D6 plays an important role in the metabolism of many drugs such as opioids and antidepressants. Polymorphisms of the CYP2D6 gene are widely observed in the Japanese population, and can affect the first-pass metabolism of orally administered drugs. Several CYP enzymes have been identified in the small intestine of Caucasians, but intestinal CYP enzymes have not been reported in the Japanese population, except for CYP3A4 and CYP2C19. In this study, we evaluated the CYP2D6 metabolic capacity by measurement of CYP2D6 mRNA and protein levels and activity in the small intestine of Japanese individuals. Normal jejunal tissues were obtained from 31 patients who had undergone pancreaticoduodenectomy, and the CYP2D6*10 variant was identified in these tissues. CYP2D6 mRNA and CYP2D6 protein levels were analyzed using real-time RT-PCR and Western blotting, respectively. Bufuralol 1'-hydroxylation, a marker of CYP2D6 activity, was analyzed using HPLC. Frequencies of the CYP2D6*1/*1, *1/*10, and *10/*10 genotypes in the jejunal tissue were 29.0% (n=9), 35.5% (n=11), and 35.5% (n=11), respectively. CYP2D6 protein and activity levels did not differ significantly between the genotypes. A positive correlation was found between CYP2D6 protein and activity levels. Furthermore, CYP2D6 protein levels and activity in the small intestine were significantly lower than those in the liver. These findings suggest that the metabolic capacity of CYP2D6 in the small intestine of the Japanese population has a relatively small effect on drug metabolism.
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http://dx.doi.org/10.1248/bpb.b16-00370DOI Listing
September 2017

Utility of Glissonean Pedicle Transection for Surgical Treatment of Severe Liver Trauma.

Case Rep Gastroenterol 2017 Jan-Apr;11(1):190-200. Epub 2017 Apr 10.

aDivision of Gastroenterological and General Surgery, St. Marianna University School of Medicine, Miyamae-ku, Japan.

The most common initial strategy for treatment of severe liver trauma is damage control in which hemostasis is achieved by perihepatic gauze packing and/or vascular embolization. However, we encounter patients in whom this strategy alone is not adequate. We have applied the principles of Glissonean pedicle transection, a technique that was originally devised to ensure safe and quick performance of planned hepatectomy for liver cancer, to 3 cases of severe liver trauma. We performed Glissonean pedicle ligation during damage control surgery in 2 patients and Glissonean pedicle transection during the definitive surgery in 1 patient. We describe the approaches and our experience with them, including operation times and outcomes. From our experience thus far, it seems that 8-12 h after the damage control procedure is appropriate for performing the definitive surgery. Although there are some problems posed by this strategy and cases to which it will not be applicable, the method seems to be particularly useful for cases of severe liver trauma in which the damage is extensive and involves the Glissonean pedicles near the hepatic hilus. We describe our 3 cases in detail and review our experience in light of the available literature.
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http://dx.doi.org/10.1159/000468514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422731PMC
April 2017

Mechanisms for the anti-obesity actions of bofutsushosan in high-fat diet-fed obese mice.

Chin Med 2017 27;12. Epub 2017 Mar 27.

Center of Clinical Pharmacy Education, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, 920-1181 Japan.

Background: The Kampo medicine bofutsushosan (BTS; ; ) has been used as an anti-obesity treatment in overweight patients. In this study, we assessed the underlying physiological changes induced by BTS in obese mice maintained on a high-fat diet.

Methods: Male ICR mice were fed a 60% kcal fat diet for 5 weeks starting at 4 weeks of age and then fed the same diet with administration of water (control) or aqueous BTS extract (1.0-2.0 g/kg) for 25 days. Body weight, wet weight of isolated white adipose tissue, and obesity-related serum parameters (glucose, lipids, leptin, adiponectin) were measured after treatment. The mRNA expression levels of leptin, adiponectin, and UCP1 in the adipose tissues were determined by quantitative real-time polymerase chain reaction after the first 5 days of treatment.

Results: Bofutsushosan (1.5-2.0 g/kg) significantly decreased total body weight and total wet weight of white adipose tissue isolated from subcutaneous (retroperitoneal) and visceral regions (epididymal, mesenteric, and perirenal). At 2.0 g/kg, BTS also decreased total fat mass, visceral fat mass, and ratio of fat mass to body weight as measured by computed tomography, and significantly decreased epididymal adipocyte size after 14 and 25 days' treatment. Twenty-five days' treatment lowered serum glucose, insulin, leptin, and triglycerides, and reduced homeostasis model assessment-insulin resistance. Alternatively, 2.0 g/kg BTS significantly increased mRNA levels of adiponectin, leptin, and UCP1 in interscapular brown adipose tissue but not epididymal white adipose tissue after 5 days' administration.

Conclusion: In the early administration period, BTS increased mRNA expression levels of leptin, adiponectin, and UCP1 in brown adipose tissues. With longer administration, BTS improved insulin resistance, and subsequently reduced serum levels of leptin and triglyceride in parallel with decreased visceral white adipose tissue volume and adipocyte size.
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http://dx.doi.org/10.1186/s13020-017-0129-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369197PMC
March 2017

Safety-related outcomes of the Japanese Society of Hepato-Biliary-Pancreatic Surgery board certification system for expert surgeons.

J Hepatobiliary Pancreat Sci 2017 May 26;24(5):252-261. Epub 2017 Apr 26.

President of the JSHBPS, Tokyo, Japan.

Background: We investigated safety-related outcomes of hepatobiliary pancreatic (HBP) surgeries performed after establishment of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) board certification system for expert surgeons.

Methods: We analyzed post-HBP surgery mortality data obtained from annual safety reports provided by board-certified training institutions between 2012 and 2015.

Results: The 90-day mortality rate for the 53,929 high-level HBP surgeries performed at board-certified training institutions was 1.7%. The 30-day mortality rates for 2012, 2013, 2014, and 2015 were 0.9%, 0.7%, 0.6%, and 0.6%, respectively, and the 90-day mortality rates were 2.1%, 1.8%, 1.6%, and 1.3%, respectively, with significant decreases in both. The surgeries with high 4-year cumulative mortality rates were left hepatic trisectionectomy (10.3%), hepatopancreatectomy (7.6%), liver transplant recipient surgery (6.7%), hepatectomy with extrahepatic bile duct resection (4.6%), and right hepatic trisectionectomy (4.5%). Over the 4-year period, the number of operations increased, but the 90-day mortality rates for these surgeries, with the exception of right trisectionectomy, decreased.

Conclusions: The JSHBPS board certification system for expert surgeons has significantly decreased mortality subsequent to high-level HBP surgeries. Reducing mortality associated with high-risk HBP surgeries will be our next challenge.
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http://dx.doi.org/10.1002/jhbp.444DOI Listing
May 2017

Why Are Vinyl Cations Sluggish Electrophiles?

J Am Chem Soc 2017 02 20;139(4):1499-1511. Epub 2017 Jan 20.

Department Chemie, Ludwig-Maximilians-Universität München , Butenandtstrasse 5-13, 81377 München, Germany.

The kinetics of the reactions of the vinyl cations 2 [PhC═C-(4-MeO-CH)] and 3 [MeC═C-(4-MeO-CH)] (generated by laser flash photolysis) with diverse nucleophiles (e.g., pyrroles, halide ions, and solvents containing variable amounts of water or alcohol) have been determined photometrically. It was found that the reactivity order of the nucleophiles toward these vinyl cations is the same as that toward diarylcarbenium ions (benzhydrylium ions). However, the reaction rates of vinyl cations are affected only half as much by variation of the nucleophiles as those of the benzhydrylium ions. For that reason, the relative reactivities of vinyl cations and benzhydrylium ions depend strongly on the nature of the nucleophiles. It is shown that vinyl cations 2 and 3 react, respectively, 227 and 14 times more slowly with trifluoroethanol than the parent benzhydrylium ion (Ph)CH, even though in solvolysis reactions (80% aqueous ethanol at 25 °C) the vinyl bromides leading to 2 and 3 ionize much more slowly (half-lives 1.15 yrs and 33 days) than (Ph)CH-Br (half-life 23 s). The origin of this counterintuitive phenomenon was investigated by high-level MO calculations. We report that vinyl cations are not exceptionally high energy intermediates, and that high intrinsic barriers for the sp ⇌ sp rehybridizations account for the general phenomenon that vinyl cations are formed slowly by solvolytic cleavage of vinyl derivatives, and are also consumed slowly by reactions with nucleophiles.
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http://dx.doi.org/10.1021/jacs.6b10889DOI Listing
February 2017

Incomplete Annular Pancreas with Ectopic Opening of the Pancreatic and Bile Ducts into the Pyloric Ring: First Report of a Rare Anomaly.

Case Rep Gastroenterol 2016 May-Aug;10(2):373-380. Epub 2016 Jul 29.

Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine, Kawasaki, Japan.

The patient was a 56-year-old woman who had experienced epigastralgia and dorsal pain several times over the last 20 years. She was admitted for a diagnosis of acute cholecystitis, and severe intra- and extrahepatic bile duct dilatation with inner air density was noted. No papilla of Vater was present in the descending duodenum, and 2 small holes were present in the pyloric ring. Bile excretion from one of the small holes was observed under forward-viewing endoscope. It was considered that the pancreatic and bile ducts separately opened into the pyloric ring. Based on these findings, malformation of the pancreaticobiliary duct was diagnosed. She did not wish treatment, but the obstruction associated with duodenal stenosis was noted after 2 years. Pancreatoduodenectomy was performed as curative treatment for duodenal stenosis and retrograde biliary infection through the bile duct opening in the pyloric ring. The ventral pancreas encompassed almost the entire circumference of the pyloric ring, suggesting a subtype of annular pancreas. Generally, lesions are present in the descending part of the duodenum in an annular pancreas, and the pancreatic and bile ducts join in the papillary region. However, in this patient, (1) the pancreas encompassed the pyloric ring, (2) the pancreatic and bile ducts opened separately, and (3) the openings of the pancreatic and bile ducts were present in the pyloric ring. The pancreas and biliary tract develop through a complex process, which may cause various types of malformation of the pancreaticobiliary system, but no similar case report was found on a literature search. This case was very rare and could not be classified in any type of congenital anomaly of the pancreas. We would classify it as a subtype of annular pancreas with separate ectopic opening of the pancreatic and bile ducts into the pyloric ring.
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http://dx.doi.org/10.1159/000447292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043290PMC
July 2016

Enteral metallic stenting by balloon enteroscopy for obstruction of surgically reconstructed intestine.

World J Gastroenterol 2015 Jun;21(24):7589-93

Kazunari Nakahara, Chiaki Okuse, Nobuyuki Matsumoto, Keigo Suetani, Ryo Morita, Yosuke Michikawa, Shun-ichiro Ozawa, Kosuke Hosoya, Fumio Itoh, Department of Gastroenterology and Hepatology, St. Marianna University, School of Medicine, Kawasaki 216-8511, Japan.

We present three cases of self-expandable metallic stent (SEMS) placement using a balloon enteroscope (BE) and its overtube (OT) for malignant obstruction of surgically reconstructed intestine. A BE is effective for the insertion of an endoscope into the deep bowel. However, SEMS placement is impossible through the working channel, because the working channel of BE is too small and too long for the stent device. Therefore, we used a technique in which the BE is inserted as far as the stenotic area; thereafter, the BE is removed, leaving only the OT, and then the stent is placed by inserting the stent device through the OT. In the present three cases, a modification of this technique resulted in the successful placement of the SEMS for obstruction of surgically reconstructed intestine, and the procedures were performed without serious complications. We consider that the present procedure is extremely effective as a palliative treatment for distal bowel stenosis, such as in the surgically reconstructed intestine.
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http://dx.doi.org/10.3748/wjg.v21.i24.7589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481457PMC
June 2015

Anatomic variations of hepatic artery and new clinical classification based on abdominal angiographic images of 1200 cases.

Hepatogastroenterology 2014 Nov-Dec;61(136):2345-8

Background/aims: There is wide variation in the branches of the hepatic artery. We aimed to classify these variations clinically on the basis of abdominal angiographic images in order to find out the suitable classification.

Methodology: Anatomic variations of the hepatic artery of 1200 patients were analyzed at Tokyo Women's Medical University from 2000 to 2010, and Classified into four categories: "Y", "I-I", "Y plus I", and "I-I plus I". Patients with a proper hepatic artery were categorized as "Y", and those without as "I-I", to describe the arteries morphologically. We denoted an accessory artery as "I", and described it as being to the left or right of "Y"; i.e., "I, Y" or "Y, I", respectively.

Results: Normal hepatic anatomy was observed in 77.2% (926 subjects), and variations were found in 22.8% (274 subjects). Of all the patients, 3.8% (45 subjects) could not be classified using Michels' classification. On the other hand, when variations were classified using our classification, all variations could be classified into either Category Y (85.6%, 1027 subjects) or Category I-I (14.4%, 173 subjects).

Conclusions: Our simplified new clinical classification of hepatic artery variants would be useful for preoperative planning in hepato-biliary-pancreatic surgery and liver transplantation.
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April 2015

Appendiceal Abscesses Reduced in Size by Drainage of Pus from the Appendiceal Orifice during Colonoscopy: A Report of Three Cases.

Case Rep Gastroenterol 2014 Sep-Dec;8(3):364-70. Epub 2014 Nov 20.

Division of Gastroenterological and General Surgery, St. Marianna University School of Medicine, Kawasaki, Japan.

Interval appendectomy (IA) for appendiceal abscesses is useful for avoiding extended surgery and preventing postoperative complications. However, IA has problems in that it takes time before an abscess is reduced in size in some cases and in that elective surgery may result in a delay in treatment in patients with a malignant tumor of the appendix. In order to rule out malignancy, we performed colonoscopy on three patients with an appendiceal abscess that did not decrease in size 5 or more days after IA. After malignancy had been ruled out by examination of the area of the appendiceal orifice, the appendiceal orifice was compressed with a colonoscope, and a catheter was inserted through the orifice. Then, drainage of pus was observed from the appendiceal orifice into the cecal lumen. Computed tomography performed 3 days after colonoscopy revealed a marked reduction in abscess size in all patients. No endoscopy-related complication was noted. Colonoscopy in patients with an appendiceal abscess may not only differentiate malignant tumors, but also accelerate reduction in abscess size.
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http://dx.doi.org/10.1159/000369549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322694PMC
February 2015
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