Publications by authors named "Takehito Otsubo"

85 Publications

Surgical Outcomes of Colorectal Cancer Surgery for ≥ 85-year-old Patients in Our Hospital: Retrospective Comparison of Short- and Long-term Outcomes with Younger Patients.

J Anus Rectum Colon 2021 29;5(3):247-253. Epub 2021 Jul 29.

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

Objectives: To evaluate future problems in colorectal cancer surgery for elderly patients.

Methods: We conducted a retrospective review of patients receiving colorectal cancer surgery in our hospital from January 2010 to December 2018. Patients were divided into the ≥ 85-year-old patient group and the younger patient group. We compared patient backgrounds, surgical outcomes (surgical procedure, reduction of lymph node dissection range, operative duration, and blood loss), postoperative short-term outcomes (mortality, morbidity, and postoperative length of stay) and prognosis.

Results: We performed colorectal cancer surgery on 1,240 patients during the study period. Of them, 109 (8.7%) were ≥ 85 years old, and 1,131 (91.2%) were < 85 years old. The American Society of Anesthesiologists physical status (ASA-PS) was significantly poorer in the elderly group than in the younger group and patients with a history of cardiac disease and anticoagulant use were significantly more in the elderly group. The rate of reduction of lymph node dissection range was significantly higher in the elderly group (16.8% vs. 3.8%, p < 0.05). Overall morbidity was significantly higher in the elderly group (42.2% vs. 21.9%, p < 0.05), as were the respective frequencies of pneumonia and thromboembolism (8.2% vs. 0.7%, p < 0.05 and 3.6% vs. 0.8%, p < 0.05, respectively). Postoperative hospital stay was significantly longer in the elderly group (17 vs. 12 days, p < 0.05). Overall survival was significantly lower in the elderly group (p < 0.05), but relapse-free survival and colorectal cancer-specific survival were not statistically different between the groups (p = 0.05 and p = 0.15, respectively).

Conclusions: Prevention of postoperative pneumonia and thromboembolism remains a problem. After proper assessment and careful management of peri-operative surgical risks, surgery can be indicated in elderly patients.
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http://dx.doi.org/10.23922/jarc.2020-095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321587PMC
July 2021

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

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

Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-Label Multicenter Prospective Trial (JASPAC05).

Ann Surg 2020 Oct 15. Epub 2020 Oct 15.

Department of Hepato-biliary Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Objective: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in borderline resectable pancreatic cancer (BRPC).

Summary Background Data: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established.

Methods: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a one-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively.

Results: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively.

Conclusions: S-1 and concurrent radiotherapy appear to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC.

Trial Registration: UMIN000009172.
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http://dx.doi.org/10.1097/SLA.0000000000004535DOI Listing
October 2020

An extremely rare case of neuromuscular and vascular hamartoma of the appendix.

Surg Case Rep 2020 Aug 24;6(1):216. Epub 2020 Aug 24.

Department of Gastroenterological and General Surgery, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kasawaki, Japan.

Background: Neuromuscular and vascular hamartoma is a rare lesion of the small intestine, with only 26 cases reported since its initial description in 1982. No occurrence of hamartoma in the appendix has been reported until now.

Case Presentation: A 60-year-old man had been suffering from longstanding right lower quadrant pain. Abdominal computed tomography showed a slight swelling of the appendix as the possible cause of his pain. Laparoscopic appendectomy with partial resection of the cecum was performed for diagnostic and therapeutic purposes. An 18 × 10-mm lesion located on the tip of the appendix was found in the resected specimen. Pathological examination showed that the lesion was covered with normal mucosa and consisted of adipose tissue, smooth muscle fibers, small vessels, and neural fibers. These findings were consistent with neuromuscular and vascular hamartoma of the appendix.

Conclusion: This is the first report of neuromuscular and vascular hamartoma arising from the appendix.
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http://dx.doi.org/10.1186/s40792-020-00970-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445220PMC
August 2020

Level of total bilirubin in the bile of the future remnant liver of patients with obstructive jaundice undergoing hepatectomy predicts postoperative liver failure.

J Hepatobiliary Pancreat Sci 2020 Sep 2;27(9):614-621. Epub 2020 Jul 2.

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Background: We investigated whether the daily level of total bilirubin in the bile (LTB) excreted from the future remnant liver (FRL) can predict post-hepatectomy liver failure (PHLF) in patients with obstructive jaundice undergoing hepatectomy.

Methods: Seventy-four patients who underwent biliary drainage and collection of bile juice from the FRL before undergoing right hepatectomy or right/left trisectionectomy with bile duct resection were included. The LTB from the FRL (mg/d) was calculated as the volume of the bile (dL) per day multiplied by the density of total bilirubin in the bile (mg/dL). We compared patients' characteristics with or without PHLF, which was defined as the total serum bilirubin level remaining >10 mg/dL after postoperative day 10. Then, pre- and intraoperative factors related to PHLF were examined.

Results: PHLF was observed in six patients. LTB was significantly lower in the PHLF group. The LTB cut-off value for predicting PHLF, as determined using the receiver operating characteristic curve, was 56 mg/d. On multivariate analysis, LTB was found to be an independent risk factor for PHLF (P = .01, OR 35.88).

Conclusions: LTB may be a potential functional assessment in jaundiced patients before right hepatectomy and right/left trisectionectomy.
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http://dx.doi.org/10.1002/jhbp.784DOI 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

Des-gamma-carboxy prothrombin affects the survival of HCC patients with marginal liver function and curative treatment: ACRoS1402.

J Cancer Res Clin Oncol 2020 Nov 27;146(11):2949-2956. Epub 2020 May 27.

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.

Purpose: Considering the initial treatment of hepatocellular carcinoma (HCC), the best prognostic index for Child-Pugh classes B and C (CP-BC) patients has not been yet established. This study aimed to elucidate the risk factors for disease-free survival (DFS) and overall survival (OS) in multicenter patients with a poor liver functional reserve after curative treatment.

Methods: Between April 2000 and April 2014, 212 CP-BC patients who received treatment in five high-volume centers in Japan were included in this study. CP-B and C patients were 206 and 6, respectively. Cox proportional hazard regression analyses for DFS and OS were performed to estimate the risk factors.

Results: The mean observation time was 1132 days. Mean Child-Pugh score and indocyanine green retention rate at 15 min were 7.5 and 31.5%, respectively. Histological chronic hepatitis and liver cirrhosis were observed in 20% and 74% patients, respectively. In the multivariate analysis, the risk factors for DFS were des-gamma-carboxy prothrombin (DCP) [hazard ratio (HR), 1.6; P = 0.012] and treatment without liver transplantation. Moreover, DCP was identified as an independent risk factor for OS (HR, 1.7; P = 0.01). Tumor size, number, tumor thrombus, Milan criteria, liver cirrhosis, and treatment without liver transplantation were not identified as risk factors for OS. The 5-year OS in patients with high serum DCP levels (< 90 mAU/mL) was significantly better than that in those with low serum DCP levels (P = 0.003).

Conclusions: Serum DCP value before treatment predicted both DFS and OS in CP-BC patients with HCC.
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http://dx.doi.org/10.1007/s00432-020-03270-2DOI Listing
November 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

Delayed perforation after endoscopic band ligation for colonic diverticular hemorrhage.

Clin J Gastroenterol 2020 Feb 1;13(1):6-10. Epub 2019 Aug 1.

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

A 77-year-old woman presented with the chief complaint of large amounts of hematochezia. Contrast-enhanced computed tomography (CT) revealed extravasation of contrast medium from the diverticula in the sigmoid colon; therefore, upon diagnosis of sigmoid colonic diverticular hemorrhage, she was immediately admitted to our hospital. Emergency colonoscopy revealed active bleeding from the diverticula in the sigmoid colon; hemostasis was achieved with endoscopic band ligation (EBL). However, 4 days later, she suddenly developed severe abdominal pain while defecation, prompting the requirement for obtaining a CT scan, which revealed intraabdominal free air, and delayed perforation after EBL was diagnosed. Emergency surgery was immediately performed; the perforation site was closed with sutures. EBL is useful in achieving hemostasis for colonic diverticular hemorrhage; however, it carries the risk of serious complications, such as delayed perforation, which require surgery. Although EBL is useful to achieve hemostasis for diverticular hemorrhage in the colon, it is preferable to carefully judge its indication owing to the risk of serious complications.
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http://dx.doi.org/10.1007/s12328-019-01027-0DOI Listing
February 2020

High-signal-intensity MR Image in the Hepatobiliary Phase Predicts Long-term Survival in Patients With Hepatocellular Carcinoma.

Anticancer Res 2019 Aug;39(8):4219-4225

Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan

Background/aim: The aim of the study was to evaluate surgical outcomes of patients with high-signal intensity (SI) image hepatocellular carcinoma (HCC).

Patients And Methods: Between 2008 and 2013, 257 HCC patients were retrospectively evaluated. A total of 21 patients were diagnosed as high-SI image HCC, 215 as low-SI image HCC, and 21 patients as mixed (high and low)-SI image HCC in the hepatobiliary (HB) phase of MRI. Five-year overall survival (OS) and recurrence-free survival (RFS) were compared among patient groups.

Results: The 5-year OS and RFS rates were significantly higher in patients with high-SI image HCC (100% and 56%) than in patients with low-SI image HCC (71%; p=0.097 and 38%; p=0.0209) and in patients with mixed-SI image HCC (73%; p=0.0329 and 9%; p=0.0021). High-SI image was an independent prognostic factor for OS (relative risk 0.167, p=0.0178) and RFS (relative risk 0.471, p=0.0322) on multivariate analysis.

Conclusion: Patients with high-SI image HCC showed favorable long-term survival after curative surgery.
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http://dx.doi.org/10.21873/anticanres.13583DOI Listing
August 2019

Predictive model for survival after liver resection for noncolorectal liver metastases in the modern era: a Japanese multicenter analysis.

J Hepatobiliary Pancreat Sci 2019 Oct 28;26(10):441-448. Epub 2019 Jul 28.

Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan.

Background: Survival benefit of liver resection for noncolorectal liver metastases (NCRLM) remains to be defined.

Methods: This multicenter, retrospective cohort analysis included consecutive patients with NCRLM whose primary tumor and all metastases were treated with curative intent between 2000 and 2013. The primary endpoint was 5-year overall survival. Clinicopathological factors that affected prognoses were identified using multivariate Cox regression analyses and were included in a predictive model.

Results: Data for 205 patients were analyzed. The three most common primary tumor sites were stomach (39%), pancreas (13%), and urinary tract (10%), with adenocarcinomas the main pathology (52%). R0 resection was achieved in 85%, and the overall survival at 5 years was 41%. In the multivariate analysis, synchronous liver metastases, R1/2 resection, and adenocarcinomas and other carcinomas (with gastrointestinal stromal tumors, neuroendocrine tumors G1/G2, and sarcomas set as the reference group) were independent negative indicators of overall survival. A predictive model effectively stratified the NCRLM patients into low-, intermediate-, and high-risk groups with overall 5-year survival rates of 63%, 38%, and 21%, respectively (P < 0.001).

Conclusions: Patients who underwent curative resection for metachronous disease and favorable tumor pathology are expected to have better survival in the NCRLM cohort.
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http://dx.doi.org/10.1002/jhbp.654DOI Listing
October 2019

Prone "computed tomography hernia study" for the diagnosis of inguinal hernia.

Surg Today 2019 Nov 26;49(11):936-941. Epub 2019 Jun 26.

Department of Radiology, St. Marianna University School of Medicine, 2-16-1Miyamae-ku, SugaoKawasaki, 216-8511, Kanagawa, Japan.

Purpose: To improve diagnostic accuracy in cases of a suspected inguinal hernia, we perform a "CT hernia study," with the patient lying prone to allow decompression of the structures in the inguinal region.

Methods: We reviewed the records of 914 patients with a suspected inguinal hernia who underwent prone non-contrast lower abdominal CT with two rolled-up towels, 20 cm in diameter, placed transversely beneath them, at the umbilicus and hips, respectively.

Results: The CT hernia study yielded a diagnosis of inguinal hernia in 861 (94.2%) patients and a condition other than inguinal hernia in 43 (4.7%) patients. Hernia was not detected preoperatively but found intraoperatively in 10 patients (1.1%). Surgery was performed for a collective total of 1029 hernias in 873 patients, and the CT hernia study-based hernia detection rate was 98.3%. We compared the preoperative diagnoses of various types of hernia (Japanese Hernia Society Types I-V) against the intraoperative diagnoses and found that the CT hernia study yielded 95.8% accuracy.

Conclusion: The CT hernia study appears to provide a high detection rate and makes differentiating the various types of inguinal hernia possible. We believe our CT hernia study adds a level of objectivity that is diagnostically beneficial.
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http://dx.doi.org/10.1007/s00595-019-01837-2DOI Listing
November 2019

An Investigation of Factors Related to Food Intake Ability and Swallowing Difficulty After Surgery for Thoracic Esophageal Cancer.

Dysphagia 2019 08 29;34(4):592-599. Epub 2019 Apr 29.

Department of Rehabilitation Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.

Swallowing difficulty is among the major complications that can occur after surgery for thoracic esophageal cancer. Recurrent laryngeal nerve paralysis (RLNP) has been considered the most significant cause of a postoperative swallowing difficulty, but association between the two has not been adequately explained. We investigated the relation between postoperative RLNP and swallowing difficulty by means of video fluoroscopy. Our study included 32 patients who underwent subtotal esophagectomy for thoracic esophageal cancer at St. Marianna University School of Medicine between April 2014 and March 2017. We evaluated patients' age and sex, disease stage, preoperative presence of a swallowing difficulty, nutritional status, extent and duration of surgery, blood loss volume, and postoperative presence of RLNP and/or hoarseness. Patients were divided into two groups according to whether oral food intake was possible when video fluoroscopy was performed on postoperative day (POD) 7, and we analyzed the associated factors. Postoperative RLNP occurred in 21 patients (65.6%); hoarseness occurred in 19 (59.4%). Eleven patients (34.4%) suffered swallowing difficulty that prevented food intake. No significant association was found between postoperative swallowing difficulty and postoperative RLNP or hoarseness, but a significant relation was found between the prognostic nutritional index and intraoperative lymph node dissection. Multivariable analysis revealed a significant relation between postoperative swallowing difficulty and only one factor: cervical lymph node dissection (P = 0.0075). There appears to be no relation between RLNP pursuant to esophageal cancer surgery and swallowing difficulty that prevents oral food intake.
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http://dx.doi.org/10.1007/s00455-019-10010-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658580PMC
August 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

Vasoactive intestinal peptide increases apoptosis of hepatocellular carcinoma by inhibiting the cAMP/Bcl-xL pathway.

Cancer Sci 2019 Jan 4;110(1):235-244. Epub 2018 Dec 4.

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

Vasoactive intestinal peptide (VIP) is a modulator of inflammatory responses. VIP receptors are expressed in several tumor types, such as colorectal carcinoma. The study described herein was conducted to confirm the presence of VIP and its receptors (VPAC1 and VPAC2) in surgically resected hepatocellular carcinoma (HCC) tissues and in the HCC cell line Huh7. The mechanism responsible for apoptosis of HCC cells was then examined because VIP treatment (10  M) significantly suppressed proliferation of Huh7 cells. In examining apoptosis-related proteins, we found caspase-3 to be significantly increased and Bcl-xL and cyclic AMP (cAMP) response element-binding protein (CREB) to be significantly decreased in Huh7 cells cultured with VIP. Furthermore, the CREB level and phosphorylation were reduced. These effects were reversed by the addition of VIP receptor antagonist or cAMP antagonist Rp-cAMPS. Pretreatment with cAMP analogue blocked the increased apoptosis, suggesting that VIP induces apoptosis via a PKA-independent signaling mechanism. Our data indicate that VIP prevents the progression of HCC by apoptosis through the cAMP/Bcl-xL pathway.
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http://dx.doi.org/10.1111/cas.13861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317926PMC
January 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

Dysregulation of miRNA in chronic hepatitis B is associated with hepatocellular carcinoma risk after nucleos(t)ide analogue treatment.

Cancer Lett 2018 10 17;434:91-100. Epub 2018 Jul 17.

Department of Molecular Biology, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address:

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Nucleos(t)ide analogue (NA) therapy effectively reduces the incidence of HCC, but it does not completely prevent the disease. Here, we show that dysregulation of microRNAs (miRNAs) is involved in post-NA HCC development. We divided chronic hepatitis B (CHB) patients who received NA therapy into two groups: 1) those who did not develop HCC during the follow-up period after NA therapy (no-HCC group) and 2) those who did (HCC group). miRNA expression profiles were significantly altered in CHB tissues as compared to normal liver, and the HCC group showed greater alteration than the no-HCC group. NA treatment restored the miRNA expression profiles to near-normal in the no-HCC group, but it was less effective in the HCC group. A number of miRNAs implicated in HCC, including miR-101, miR-140, miR-152, miR-199a-3p, and let-7g, were downregulated in CHB. Moreover, we identified CDK7 and TACC2 as novel target genes of miR-199a-3p. Our results suggest that altered miRNA expression in CHB contributes to HCC development, and that improvement of miRNA expression after NA treatment is associated with reduced HCC risk.
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http://dx.doi.org/10.1016/j.canlet.2018.07.019DOI Listing
October 2018

Esophagogastric varices were diagnosed in a non-cirrhotic liver case during long-term follow-up after oxaliplatin-based chemotherapy.

Clin J Gastroenterol 2018 Dec 11;11(6):487-492. Epub 2018 Jun 11.

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

Oxaliplatin, a chemotherapeutic agent for colorectal cancer, has been associated with pathological evidence of sinusoidal endothelial injury in the liver. However, esophagogastric varices are a poorly recognized outcome of oxaliplatin-based chemotherapy. We report a 78-year-old man, whose past history of colon cancer was resection and treatment with mFOLFOX6 for 20 weeks, as adjuvant chemotherapy. After 3.5-year follow-up of the oxaliplatin-based chemotherapy, he was diagnosed with esophageal varices without liver dysfunction, indicating that the hepatotoxicity caused by oxaliplatin could be prolonged after its administration. Patients who have received oxaliplatin-based chemotherapy should be followed up carefully over the long term.
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http://dx.doi.org/10.1007/s12328-018-0873-1DOI Listing
December 2018

Augmented rectangle technique for Billroth I anastomosis in totally laparoscopic distal gastrectomy for gastric cancer.

Surg Endosc 2018 09 18;32(9):4011-4016. Epub 2018 Jun 18.

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

Background: Billroth I reconstruction is a means of anastomosis that is widely performed after surgical resection for distal gastric cancer. Interest has grown in totally laparoscopic gastrectomy, and several methods for totally laparoscopic performance of Billroth I reconstruction have been reported. However, the methods are cumbersome, and postoperative complications such as twisting at the site of anastomosis and obstruction due to stenosis have arisen. We developed an augmented rectangle technique (ART) by which the anastomosis is created laparoscopically with the use of three automatic endoscopic linear staplers, and the resulting anastomotic opening is wide and less likely to become twisted or stenosed. The technical details of our ART-based Billroth I anastomosis are presented herein along with results of the procedure to date.

Methods: The technique was applied in 160 patients who underwent totally laparoscopic distal gastrectomy for gastric cancer between December 2013 and August 2017. Clinicopathological data, surgical data, and postoperative outcomes were analyzed.

Results: During surgery, there were no troubles associated with gastrointestinal reconstruction and there was no transition to laparotomy. There were no postoperative complications, including suture failure and stenosis, associated with the gastrointestinal reconstruction, and the average postoperative hospital stay was 12 days.

Conclusion: Totally laparoscopic ART-based Billroth I reconstruction is both feasible and safe. We expect this technique to contribute to the spread of safe totally laparoscopic surgery for gastric cancer.
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http://dx.doi.org/10.1007/s00464-018-6266-1DOI Listing
September 2018

Triple-stapled quadrilateral anastomosis: a new technique for creation of an esophagogastric anastomosis.

Esophagus 2018 04 16;15(2):88-94. Epub 2017 Dec 16.

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

Background: Esophagogastric anastomosis performed after esophagectomy is technically complex and often the source of postoperative complications. The best technique for this anastomosis remains a matter of debate. We describe a new all-stapled side-to-side anastomosis, which we refer to as triple-stapled quadrilateral anastomosis (TRIQ), that can be performed after minimally invasive surgery, and we report results of a retrospective evaluation of postoperative outcomes among the 60 patients in whom this anastomosis has been performed thus far.

Methods: The anastomosis is created by apposition of the posterior walls of the esophagus and stomach. A linear stapler is applied to create a V-shaped posterior anastomotic wall. The anterior wall is closed in a gentle chevron-like shape with the use of 2 separate linear staplers, resulting in a wide quadrilateral anastomosis. The anastomosis is then wrapped with a greater omentum flap.

Results: The patient group comprised 48 men and 12 women with a mean age of 67.8 years. Neoadjuvant chemotherapy was performed in 43 of these patients. Neither the thoracoscopic or laparoscopic procedure was converted to open surgery in any patient. The median operation time was 474 min (range 680-320 min). The intraoperative blood loss volume was 104.4 mL (range 240-30 mL). There were no anastomosis-related complications above Clavien-Dindo grade II.

Conclusions: TRIQ can be performed easily and safely, and good short-term outcome can be expected.
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http://dx.doi.org/10.1007/s10388-017-0599-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884892PMC
April 2018

[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

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
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