Publications by authors named "Tomohisa Yamamoto"

81 Publications

Validation of the triple-checked criteria for drain management after pancreatectomy.

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

Department of Surgery, Kansai Medical University, Hirakata, Japan.

Background: Drain management is important for the detection and treatment of clinically relevant postoperative pancreatic fistula (CR-POPF). We previously established the triple-checked criteria for drain removal: drain fluid amylase (DFA) <5000 U/L on postoperative day (POD) 1 and DFA <3000 U/L on POD 3, or C-reactive protein <15 mg/dL on POD 3. This study aimed to validate the efficacy of the triple-checked criteria.

Methods: In this study, 681 patients who underwent pancreatectomy were included. Drains were removed according to our previous criteria (sequentially checked criteria: DFA <5000 U/L on POD 1 and DFA <3000 U/L on POD 3) from 2012 to 2016 (control group) and the triple-checked criteria from 2017 to 2019 (intervention group).

Results: The control group included 406 patients, and the intervention group included 275 patients. Significantly more patients (n = 237, 86.2%) met the triple-checked criteria in the intervention group, relative to the sequentially checked criteria for early drain removal policy (n = 309, 76.1%; P = .001). Sensitivity, accuracy, and negative predictive value were significantly higher in the intervention group than in the control group (P < .001). The incidence of CR-POPF was not significantly different (11.1% vs 13.8%, P = .285).

Conclusions: The triple-checked criteria contributed to effective drain removal after pancreatectomy without increasing CR-POPF.
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http://dx.doi.org/10.1002/jhbp.1030DOI Listing
July 2021

Hepatic actinomycosis after total pancreatectomy: A case report.

Int J Surg Case Rep 2021 Aug 20;85:106212. Epub 2021 Jul 20.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Introduction And Importance: Hepatic actinomycosis (HA) is a rare infection mimicking a malignancy. HA after total pancreatectomy for a pancreatic tumor has not been reported.

Case Presentation: A 70-year-old woman with a history of gastrectomy and sigmoidectomy for benign lesions, underwent a total pancreatectomy for a non-invasive, intraductal papillary mucinous carcinoma (IPMC). She required partial resection of the transverse colon due to insufficient blood flow and had an anastomotic failure. Four months later, she developed a fever and effusion from the upper abdominal midline incision. No bacteria were cultured from the effusion. Contrast-enhanced computed tomography demonstrated an 80-mm iso-vascular liver mass. A slightly high-signal intensity on T2-weighted magnetic resonance imaging was demonstrated. Positron emission tomography (PET) showed a standardized uptake value of 11.9 at the liver mass. The percutaneous liver biopsy did not establish a diagnosis. Because a malignancy could not be ruled out, an exploratory laparotomy was performed. A tissue sample revealed aggregates of branched filamentous microorganisms; actinomycosis was diagnosed. Oral amoxicillin for 4 months resolved the mass.

Clinical Discussion: This patient had several causative factors for HA, including multiple surgical procedures involving the gastrointestinal tract, reconstruction of the biliary tract, anastomotic failure of the transverse colon, and diabetes mellitus following total pancreatectomy. Based on the past treatment history for IPMC and PET findings mimicking a malignancy, a laparotomy was performed to biopsy the lesion. Typically, penicillin is recommended for >6 months.

Conclusion: A rare case of HA mimicking a malignancy after a total pancreatectomy for IPMC is presented.
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http://dx.doi.org/10.1016/j.ijscr.2021.106212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335620PMC
August 2021

A simple risk score for detecting radiological occult metastasis in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma.

J Hepatobiliary Pancreat Sci 2021 Jul 27. Epub 2021 Jul 27.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Background: We advocated carbohydrate antigen (CA) 19-9 ≥ 150 U/mL and tumor size ≥30 mm as "high-risk markers" for predicting unresectability among patients with radiologically resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). The main aim is to establish a risk scoring system for occult abdominal metastasis (OAM) in R/BR PDAC.

Methods: Predictors of OAM were investigated retrospectively in an experiment cohort from 2006 to 2018. The proposed risk scoring system was validated in another cohort from 2019 to 2020.

Results: Five hundred and thirteen eligible patients were divided into the experimental (405 patients; OAM, 22%) and validation cohorts (108 patients). Multivariate analysis identified tumor location of body/tail (odds ratio [OR] 4.45, P < .0001) and "high-risk markers" (OR 2.07, P = .011) as independent predictors of OAM. A scoring system consisting of body/tail (yes: 1, no: 0) and "high-risk markers" (yes: 1, no: 0) was constructed. In the validation cohort, when staging laparoscopy (SL) was performed for patients with scores 1/2, the eligibility for SL, sensitivity, and negative predictive value of OAM were 55%, 91%, and 96%, respectively.

Conclusions: Tumor location of body/tail and "high-risk markers" were independent predictors of OAM, composing our simple and reproducible risk scoring system.
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http://dx.doi.org/10.1002/jhbp.1026DOI Listing
July 2021

Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113.

Sci Rep 2021 Jun 18;11(1):12885. Epub 2021 Jun 18.

Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan.

JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504-0.937) in the low CCr group. Although the total number of incidences of all Grade 3-4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.
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http://dx.doi.org/10.1038/s41598-021-92166-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213853PMC
June 2021

Nutritional impact of active hexose-correlated compound for patients with resectable or borderline-resectable pancreatic cancer treated with neoadjuvant therapy.

Surg Today 2021 Jun 4. Epub 2021 Jun 4.

Department of Surgery, Kansai Medical University, 2-5-1 Shin-machi, Hirakata-City, Osaka, 573-1010, Japan.

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.
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http://dx.doi.org/10.1007/s00595-021-02308-3DOI Listing
June 2021

Clinicopathological characteristics of pancreatic ductal adenocarcinoma with invasive micropapillary carcinoma component with emphasis on the usefulness of PKCζ immunostaining for detection of reverse polarity.

Oncol Lett 2021 Jul 13;22(1):525. Epub 2021 May 13.

Department of Surgery, Kansai Medical University, Hirakata, Osaka 573-1010, Japan.

Invasive micropapillary carcinoma (IMPC) is a rare distinct histopathological subtype, characterized by the presence of carcinoma cells displaying reverse polarity. Only limited clinicopathological information is available regarding pancreatic IMPC. The aim of the present study was to clarify the clinicopathological features of pancreatic IMPC and the usefulness of protein kinase C (PKC)ζ immunostaining for the detection of reverse polarity. We reviewed 242 consecutive surgically resected specimens of pancreatic ductal adenocarcinoma and selected samples with an IMPC component. Clinicopathological characteristics were compared between the IMPC and non-IMPC groups. Immunohistochemical staining for PKCζ was performed using an autostainer. In total, 14 cases had an IMPC component (5.8%). The extent of IMPC component ranged from 5 to 20%. There were no significant differences in tumor location, T category, lymph node metastatic status, preoperative carbohydrate antigen 19-9 level, resection status and overall survival between the IMPC and non-IMPC groups. Immunostaining for PKCζ clearly showed reverse polarity of the neoplastic cells of IMPC. Although previous reports have shown that the presence of an IMPC component (>20% of the tumor) indicated poor prognosis, the present study demonstrated that presence of IMPC <20% did not suggest a worse prognosis.
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http://dx.doi.org/10.3892/ol.2021.12786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138900PMC
July 2021

Conversion surgery in patients with pancreatic cancer and peritoneal metastasis.

J Gastrointest Oncol 2021 Apr;12(Suppl 1):S110-S117

Department of Surgery, Kansai Medical University, Hirakata, Japan.

Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies globally. We have previously explored the clinical efficacy of intraperitoneal (IP) paclitaxel therapy for patients with PDAC and peritoneal metastasis, which demonstrated favourable response and disease control rates. However, the real implications of conversion surgery after IP therapy remain unclear.

Methods: We conducted two multicenter clinical trials of IP therapy with paclitaxel in patients with PDAC and peritoneal metastasis. We focused on patients who underwent conversion surgery and investigated the long-term outcomes, particularly, initial recurrence patterns and long-term survival.

Results: Seventy-nine patients with PDAC and peritoneal metastasis were treated, and 33 (41.8%) patients received SP (intravenous IP paclitaxel with S-1) and 46 (58.3%) were administered GAP (intravenous gemcitabine + nab-paclitaxel combined with IP paclitaxel) combination therapy. Of the 79 patients, 16 (20.3%) underwent conversion surgery. The median time to surgery was 9.0 (range, 4.1-13.0) months after the initiation of chemotherapy. Finally, 13 (81.3%) patients underwent R0 resection. Evans grade was IIA in nine patients, IIB in four patients, III in two patients, and IV in one patient. The median overall survival time in patients who underwent conversion surgery was 32.5 (range, 13.5-66.9) months. Twelve (75.0%) patients were found to have experienced recurrence after conversion surgery. Especially, peritoneal recurrence was observed in 50% of patients as the initial recurrence pattern. The median recurrence-free survival time was 9.2 (range, 5.1-32.8) months, and three patients have survived without recurrence to date.

Conclusions: Our IP therapy displays promising clinical efficacy with acceptable tolerability in patients with PDAC and peritoneal metastasis. Although we could observe some super-responders in the cohort, further improvements in IP therapy are warranted.
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http://dx.doi.org/10.21037/jgo-20-243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100706PMC
April 2021

Does direct invasion of peripancreatic lymph nodes impact survival in patients with pancreatic ductal adenocarcinoma? A retrospective dual-center study.

Pancreatology 2021 Aug 19;21(5):884-891. Epub 2021 Mar 19.

Department of Surgery, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.

Background: Pancreatic ductal adenocarcinoma can directly invade the peripancreatic lymph nodes; however, the significance of direct lymph node invasion is controversial, and it is currently classified as lymph node metastasis. This study aimed to identify the impact of direct invasion of peripancreatic lymph nodes on survival in patients with pancreatic ductal adenocarcinoma.

Methods: A total of 411 patients with resectable/borderline resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection at two high-volume centers from 2006 to 2016 were evaluated retrospectively.

Results: Sixty (14.6%) patients had direct invasion of the peripancreatic lymph nodes without isolated lymph node metastasis (N-direct group), 189 (46.0%) had isolated lymph node metastasis (N-met group), and 162 (39.4%) had neither direct invasion nor isolated metastasis (N0 group). There was no significant difference in median overall survival between the N-direct group (35.0 months) and the N0 group (45.6 month) (p = 0.409), but survival was significantly longer in the N-direct compared with the N-met group (25.0 months) (p = 0.003). Similarly, median disease-free survival was similar in the N-direct (21.0 months) and N0 groups (22.7 months) (p = 0.151), but was significantly longer in the N-direct compared with the N-met group (14.0 months) (p < 0.001). Multivariate analysis identified resectability, adjuvant chemotherapy, and isolated lymph node metastasis as independent predictors of overall survival. However, direct lymph node invasion was not a predictor of survival.

Conclusion: Direct invasion of the peripancreatic lymph nodes had no effect on survival in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma, and should therefore not be classified as lymph node metastasis.
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http://dx.doi.org/10.1016/j.pan.2021.03.008DOI Listing
August 2021

Multicenter randomized phase II trial of prophylactic right-half dissection of superior mesenteric artery nerve plexus in pancreatoduodenectomy for pancreatic head cancer.

Ann Gastroenterol Surg 2021 Jan 15;5(1):111-118. Epub 2020 Sep 15.

Department of Surgery and Science Faculty of Medicine Academic Assembly University of Toyama Toyama Japan.

Aim: Right-half dissection of the superior mesenteric artery (SMA) nerve plexus in pancreatoduodenectomy for pancreatic cancer was initiated to accomplish R0 resection; however, subsequent refractory diarrhea was a major concern. This study aimed to evaluate the necessity of this technique.

Methods: From April 2014 to June 2018, 74 patients with pancreatic head cancer were randomly allocated to either Group A, in which right-half dissection of the SMA nerve plexus was performed (n = 37), or Group B, in which total preservation of the nerve plexus was performed (n = 37). Short-term, long-term, and survival outcomes were prospectively compared between the groups.

Results: The patient demographics, including the R0 resection rate, were not significantly different between the groups. Postoperative diarrhea occurred in 26 (70.3%) patients in Group A and 18 (48.6%) patients in Group B. There was a tendency for the development of severe diarrhea in Group A within 1 year postoperatively, and the frequency of diarrhea gradually decreased within 2 years, although that did not affect tolerance to adjuvant chemotherapy. There was no difference in either locoregional recurrence (27.0% vs 32.4%) or systemic recurrence (46.0% vs 46.0%). The median overall survival time in Groups A and B was 37.9 and 34.6 months, respectively ( = 0.77).

Conclusion: We did not demonstrate a clinical impact of right-half dissection of the SMA nerve plexus on locoregional recurrence or survival. Therefore, the prophylactic dissection of the SMA nerve plexus is unnecessary given that refractory diarrhea could be induced by this technique (UMIN000012241).
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http://dx.doi.org/10.1002/ags3.12399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832966PMC
January 2021

Impact of Antithrombotic Agents on Postpancreatectomy Hemorrhage: Results from a Retrospective Multicenter Study.

J Am Coll Surg 2020 10 4;231(4):460-469.e1. Epub 2020 Jul 4.

Kansai Medical University, Osaka, Japan.

Background: This retrospective multicenter study aimed to evaluate the risk of postpancreatectomy hemorrhage (PPH) in patients receiving antithrombotic agents (ATAs). PPH is the most severe complication after pancreatectomy. However, there is little known about the strength of the association between ATA use, PPH, and other clinical outcomes.

Study Design: Between 2007 and 2016, 1,297 patients underwent pancreatectomy at 2 surgical centers. ATA use included aspirin, clopidogrel, ticlopidine, warfarin, direct oral anticoagulants, and intravenous unfractionated heparin. The ATA group was composed of 144 patients who were taking ATAs before surgery.

Results: A total of 35 patients developed PPH. The patients in the ATA group showed higher frequency (8.3% vs 2.0%, p < 0.001) of PPH compared with the control group (n = 1,153). In multivariate analysis, ATA use was an independent adverse risk factor for PPH (odds ratio [OR] 3.58, 95% CI 1.29-9.91, p = 0.014). Stratification by preoperative ATA therapy revealed a significant risk of PPH Grade C in patients receiving combined AT therapy. The median onset of late hemorrhage (>24 hours post-surgery) in the ATA group was later than in the control group (17.5 vs 8.5 days, p = 0.032), and the incidence tended to be higher in patients who restarted ATAs postoperatively.

Conclusions: History of ATA use is a significant risk factor for PPH, and postoperative resumption of ATAs appears to be associated with an increased risk of PPH. Patients receiving combined antithrombotic therapy may be at particularly high risk for PPH.
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http://dx.doi.org/10.1016/j.jamcollsurg.2020.06.017DOI Listing
October 2020

Optimal Treatment for Octogenarians With Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Multicenter Retrospective Study.

Pancreas 2020 07;49(6):837-844

Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan.

Objectives: The objective of this study was to clarify the role of pancreatectomy for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma aged 80 years or older using a nationwide audit by the Japan Pancreas Society.

Methods: Data were collected from 39 institutions from 2007 to 2014. The primary endpoint was overall survival, and secondary endpoints were surgical outcomes and predictive factors for prognosis.

Results: Data were obtained from 556 octogenarians who underwent pancreatectomy (n = 369, 66%), chemo(radio)therapy (n = 99, 18%), and palliative therapy (n = 88, 16%). Median survival times were 20.6, 18.6, and 8.8 months in each group, respectively. Even after propensity score matching, median survival time in the surgery group (22.8 months) was significantly higher than that in the chemotherapy group (18.5 months; hazard ratio, 0.64 [95% confidence interval, 0.44-0.93]; P = 0.020). Significant independent prognostic factors were body mass index, lymph node metastasis, and tumor diameter in the surgery group, and serum albumin level, American Society of Anesthesiologists classification, body mass index, modified Glasgow prognostic score, second-line chemotherapy, and tumor diameter in the chemotherapy group.

Conclusions: Octogenarians with resectable/borderline resectable pancreatic ductal adenocarcinoma can be recommended for pancreatectomy according to mental and physical fitness for surgical procedures.
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http://dx.doi.org/10.1097/MPA.0000000000001579DOI Listing
July 2020

Benefits of Conversion Surgery after Multimodal Treatment for Unresectable Pancreatic Ductal Adenocarcinoma.

Cancers (Basel) 2020 May 31;12(6). Epub 2020 May 31.

Department of Surgery, Kansai Medical University, Hirakata 573-1010, Japan.

Background: Traditionally, the treatment options for unresectable locally advanced (UR-LA) and metastatic (UR-M) pancreatic ductal adenocarcinoma (PDAC) are palliative chemotherapy or chemoradiotherapy. The benefits of surgery for such patients remains unknown. The present study investigated clinical outcomes of patients undergoing conversion surgery (CS) after chemo(radiation)therapy for initially UR-PDAC.

Methods: We recruited patients with UR-PDAC who underwent chemo(radiation)therapy for initially UR-PDAC between April 2006 and September 2017. We analyzed resectability of CS, predictive parameters for overall survival, and early recurrence (within six months).

Results: A total of 468 patients (108 with UR-LA and 360 with UR-M PDAC) were enrolled in this study, of whom, 17 (15.7%) with UR-LA and 15 (4.2%) with UR-M underwent CS. The median survival time (MST) and five-year survival of patients who underwent CS was 37.2 months and 34%, respectively; significantly better than non-resected patients (nine months and 1%, respectively, < 0.0001). MST did not differ according to UR-LA or UR-M (50.5 vs. 29.0 months, respectively, = 0.53). Early recurrence after CS occurred in eight patients (18.8%). Lymph node metastasis, positive washing cytology, large tumor size (>35 mm), and lack of postoperative adjuvant chemotherapy were statistically significant predictive factors for early recurrence. Moreover, the site of pancreatic lesion and administration of postoperative adjuvant chemotherapy were statistically significant prognostic factors for overall survival in the patients undergoing CS.

Conclusion: Conversion surgery offers benefits in terms of increase survival for initially UR-PDAC for patients who responded favorably to chemo(radiation)therapy when combined with postoperative adjuvant chemotherapy.
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http://dx.doi.org/10.3390/cancers12061428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352934PMC
May 2020

Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma.

Ann Gastroenterol Surg 2020 Jan 29;4(1):6-13. Epub 2019 Oct 29.

Department of Surgery Kansai Medical University Hirakata-City Japan.

Aim of this review is to propose an acceptable surgical indication for conversion surgery in patients with initially unresectable (UR) pancreatic ductal adenocarcinoma (PDAC) by considering desirable outcomes, including resectability, overall survival (OS), and disease-free survival (DFS). A comprehensive literature search of PubMed was conducted through July 15, 2019. Eligible studies were those reporting on patients with UR-PDAC who underwent surgery. We excluded case reports with fewer than 10 patients, insufficient descriptions of survival data, and palliative surgery. When patients with UR-PDAC with no progression after chemo(radiation) therapy were offered surgical exploration, resectability and median survival time (MST) of those who underwent conversion surgery ranged from 20% to 69% (median, 52%) and from 19.5 to 33 months (median, 21.9 months), respectively. When conversion surgery was carried out in patients with expected margin-negative resection or with clinical response by Response Evaluation Criteria In Solid Tumors (RECIST), resectability and MST ranged from 18% to 27% (median, 20%) and from 21 to 35.3 months (median, 30 months), respectively. Among patients who underwent conversion surgery based on clinical response and decreased CA19-9 level after multimodal treatment, resectability and MST ranged from 2% to 24% (median, 4.1%) and from 24.1 to 64 months (median, 36 months), respectively. Decreased CA19-9 level was a predictor of resectability, OS and DFS by multivariate analysis. In conclusion, decision-making for conversion surgery based on clinical response and decreased CA19-9 level after multimodal treatment may be appropriate. With regard to desirable outcomes of OS and DFS, conversion surgery may provide improved survival for patients with initial UR-PDAC.
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http://dx.doi.org/10.1002/ags3.12295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992681PMC
January 2020

The past, present, and future status of multimodality treatment for resectable/borderline resectable pancreatic ductal adenocarcinoma.

Surg Today 2020 Apr 28;50(4):335-343. Epub 2020 Jan 28.

Department of Surgery, Kansai Medical University, 2-3-1, Shin-machi, Hirakata, Osaka, 573-1191, Japan.

A multimodal approach to treating pancreatic ductal adenocarcinoma (PDAC) is now widely accepted. Improvements in radiological assessment have enabled us to define resectability in detail. Multimodality treatment is essential for patients, especially for those with PDAC in the borderline resectable (BR) stage. Even for disease in a resectable (R) stage, adjuvant and neoadjuvant therapies have demonstrated beneficial outcomes in several trials and analyses. Thus, there is growing interest in optimization of the perioperative therapeutic strategy. We discuss the transition of resectability criteria and the global standard of adjuvant and neoadjuvant treatments for patients with R/BR-PDAC.
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http://dx.doi.org/10.1007/s00595-020-01963-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098925PMC
April 2020

Bile Duct Stones Predict a Requirement for Cholecystectomy in Older Patients.

World J Surg 2020 03;44(3):721-729

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Background: The requirement for elective cholecystectomy in older patients is unclear. To determine predictors for requiring elective cholecystectomy in older patients, a prospective cohort study was performed.

Methods: All patients with gallstone disease who presented to our department from 2006 to 2018 were included if they met the following criteria: (1) age 75 years or older, (2) presentation for elective cholecystectomy, and (3) preoperative diagnosis of cholecystolithiasis. Two therapeutic options, elective surgery and a wait-and-see approach, were offered at their initial visit. Enrolled patients were assigned to one arm of the study according to their choice of the therapeutic options. The primary endpoint was the incidence of gallstone-related complications. The endpoint was compared between patients who underwent cholecystectomy (CH group) and those who chose a wait-and-see approach (No-CH group).

Results: During the study period, there were 344 patients in the CH group and 161 in the No-CH group. Among patients with a history of bile duct stones, the incidence of gallstone-related complications in the No-CH group was significantly higher (45% within 3 years, including two gallstone-related deaths) than that in the CH group (RR 2.66, 95% confidence interval 1.50-4.77, p = 0.0009). Among patients with no history of bile duct stones, the incidence of gallstone-related complications in the No-CH group reached only 10% over the 12 years.

Conclusion: Cholecystectomy is recommended for older patients with both histories of cholecystolithiasis and bile duct stones, whereas a wait-and-see approach is preferable for patients with no bile duct stone history. A history of bile duct stones is a good predictor for cholecystectomy in older patients.
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http://dx.doi.org/10.1007/s00268-019-05241-2DOI Listing
March 2020

Clinical impact of the sequentially-checked drain removal criteria on postoperative outcomes after pancreatectomy: a retrospective study.

J Hepatobiliary Pancreat Sci 2019 Sep 23;26(9):426-434. Epub 2019 Jul 23.

Department of Surgery, Kansai Medical University, Hirakata, Japan.

Background: Strict criteria for impeccably safe drain management following pancreatectomy have not yet been developed. We evaluated the utility of the sequentially-checked drain removal criteria by comparison with conventional criteria.

Methods: Postoperative outcomes of 801 patients who underwent pancreatectomy, including 395 patients for whom drain fluid amylase (DFA) < 375U/l on postoperative day (POD) 3 (control group), were used and 406 patients for whom the sequentially-checked criteria of DFA <5,000 U/l on POD 1 and DFA <3,000 U/l on POD 3 (sequentially-checked group) were used and were retrospectively evaluated.

Results: DFA on POD 3 and fistula risk score did not differ between groups. Significantly more patients in the sequentially-checked group met the criteria (control, 63.8% vs. sequentially-checked, 76.1%, P < 0.001). The incidences of clinically relevant postoperative pancreatic fistula (CR-POPF) (17.0% vs. 11.1%), intra-abdominal abscess (21.0% vs. 9.1%) were significantly lower in the sequentially-checked group (all P < 0.05). Multivariate analysis revealed that use of the sequentially-checked criteria was significantly associated with CR-POPF (odds ratio 0.601, 95% confidence interval [CI] 0.389-0.929; P = 0.022). C-reactive protein <15 mg/dl at POD 3 was identified as an independent predictive factor for false positive CR-POPF results in the sequentially-checked group (odds ratio 0.872, 95% CI 0.811-0.939; P < 0.001); thus, this criterion was added to create the new triple-checked criteria.

Conclusions: The sequentially-checked criteria can provide safe drain management and improve postoperative outcomes.
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http://dx.doi.org/10.1002/jhbp.649DOI Listing
September 2019

Prognosis in Patients With Gallbladder Edema Misdiagnosed as Cholecystitis.

JSLS 2019 Apr-Jun;23(2)

Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan.

Background And Objectives: Edema of the gallbladder may pose a diagnostic challenge because it also occurs in patients without an indication for cholecystectomy.

Methods: We evaluated all consecutive patients with gallstone disease who presented for cholecystectomy at the Department of Surgery of Kansai Medical University from January 2006 to April 2019. Using the prospectively collected database in our department, we obtained information on patients whose final diagnoses were gallbladder edema. We identified 12 patients with gallbladder edema who were misdiagnosed with acute cholecystitis among 2661 patients and who presented for cholecystectomy for benign gallbladder diseases. The outcome of these patients was assessed to prevent unnecessary cholecystectomy.

Results: In all 12 patients, computed tomography and ultrasonographic imaging showed gallbladder wall thickening. Acute cholecystitis was suspected, and emergent cholecystectomy was performed for the first 5 patients. Of these 5 patients, 2 patients died of liver failure postoperatively. Based on the misdiagnosis in the first 5 patients, the latter 7 patients did not undergo cholecystectomy; instead, they were treated specifically for their systemic disease. To date, no cholecystitis has occurred in these 7 patients. In all misdiagnosed cases in the present report, mesh-like wall thickening was a distinctive feature of gallbladder edema on ultrasonography. We consider this feature important for distinguishing simple gallbladder edema from cholecystitis.

Conclusion: Careful evaluation of clinical symptoms and imaging findings, especially mesh-like wall thickening on ultrasonography, is necessary in this setting to prevent misdiagnosis and unnecessary cholecystectomy.
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http://dx.doi.org/10.4293/JSLS.2019.00022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6573792PMC
August 2019

Adipophilin expression is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma: An immunohistochemical analysis.

Pancreatology 2019 Apr 11;19(3):443-448. Epub 2019 Mar 11.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Objective: Adipophilin is a lipid droplet-associated protein, and its expression has been correlated with aggressive clinical behavior in some types of carcinomas, though its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified. This study aimed to evaluate the role of adipophilin in PDAC.

Methods: By immunohistochemical staining using tissue microarrays, we analyzed the expression profiles of adipophilin in 181 consecutive PDAC patients who underwent macroscopic margin-negative resection from January 2008 to December 2015. Overall survival (OS) and recurrence-free survival (RFS) were compared based on adipophilin expression, and the risk factors for OS, RFS, and early recurrence (within 6 months) were analyzed.

Results: Of the 181 evaluated patients, 51 (28.2%) were positive for adipophilin expression. A histopathological grade of 3 (p = 0.0012), higher CA19-9 level (p = 0.0016), and R1 status (p = 0.028) were significantly associated with adipophilin-positive patients who had significantly poor OS and RFS compared to those associated with adipophilin-negative patients (p = 0.0007 and p = 0.0022, respectively). They also showed a significantly higher incidence of early recurrence (p = 0.030), based on multivariate analyses.

Conclusions: Adipophilin is a potential independent prognostic marker for PDAC.
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http://dx.doi.org/10.1016/j.pan.2019.03.001DOI Listing
April 2019

Brain white matter lesions and postoperative cognitive dysfunction: a review.

J Anesth 2019 04 20;33(2):336-340. Epub 2019 Feb 20.

Department of Anesthesiology, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Osakasayama, Osaka, 589-8511, Japan.

Postoperative cognitive dysfunction (POCD) is a serious complication of anesthesia and surgery, and the major risk factor of POCD is aging. Although the exact pathophysiology of POCD remains unknown, two possible and reliable mechanisms have been proposed: neuroinflammation and neurodegeneration, i.e., amyloid β accumulation and/or tau protein phosphorylation, by surgery and/or general anesthetics. White matter lesions (WML) are produced by chronic cerebral hypoperfusion, frequently observed in elderly people, and closely related to cognitive decline. As recent studies have revealed that WML are a significant risk factor for POCD in humans, and we previously also demonstrated that persistent hypocapnea or hypotension caused neuronal damage in the caudoputamen or the hippocampus in a rat model of chronic cerebral hypoperfusion, which features global cerebral WML without neuronal damage and is recognized as a good model of human vascular dementia especially in elderly people, we hypothesize that in addition to those two previously proposed mechanisms, perioperative vital sign changes that cause reductions in cerebral blood flow might contribute to POCD in patients with WML, whose cerebral blood flow is already considerably decreased.
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http://dx.doi.org/10.1007/s00540-019-02613-9DOI Listing
April 2019

Assessment of clinical outcome of cholecystectomy according to age in preparation for the "Silver Tsunami".

Am J Surg 2019 09 25;218(3):567-570. Epub 2019 Jan 25.

Department of Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan.

Background: Recent rapid increases in the aging population have created an impending "Silver Tsunami" in advanced countries. The overall prevalence of gallstone disease and its related complications will soon increase, and there will be a larger demand for gallbladder surgery.

Methods: We examined the outcomes of cholecystectomy according to age among patients with cholelithiasis to determine how a patient's age influences the outcome of cholecystectomy. All patients with gallstone disease who presented for cholecystectomy at our institute from January 2006 to December 2018 were analyzed.

Results: All perioperative outcomes (operation length, length of hospital stay, rate of open surgery, urgent surgery, postoperative complications, incidental gallbladder cancer, postoperative hospital death, concomitant bile duct stones, and total medical costs per patient) increased as patients aged.

Conclusions: To prevent the progression of biliary disease, elective laparoscopic cholecystectomy is recommended before patients with cholelithiasis advance in age.
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http://dx.doi.org/10.1016/j.amjsurg.2019.01.021DOI Listing
September 2019

Phase II Study of the Triple Combination Chemotherapy of SOXIRI (S-1/Oxaliplatin/Irinotecan) in Patients with Unresectable Pancreatic Ductal Adenocarcinoma.

Oncologist 2019 06 24;24(6):749-e224. Epub 2019 Jan 24.

Department of Surgery, Nara Medical University, Nara, Japan.

Lessons Learned: The triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic ductal adenocarcinoma was an effective treatment that appeared to be better tolerated than the widely used FOLFIRINOX regimen.SOXIRI regimen may provide an alternative approach for advanced pancreatic cancer.

Background: In our previous phase I study, we determined the recommended dose of a biweekly S-1, oxaliplatin, and irinotecan (SOXIRI) regimen in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). This phase II study was conducted to assess the safety and clinical efficacy in patients with unresectable PDAC.

Methods: Patients with previously untreated metastatic and locally advanced PDAC were enrolled. The primary endpoint was response rate (RR). Secondary endpoints were adverse events (AEs), progression-free survival (PFS), and overall survival (OS). Patients received 80 mg/m of S-1 twice a day for 2 weeks in alternate-day administration, 150 mg/m of irinotecan on day 1, and 85 mg/m of oxaliplatin on day 1 of a 2-week cycle.

Results: Thirty-five enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8% (95% confidence interval [CI]: 10.4-40.1); median OS, 17.7 months (95% CI: 9.8-22.0); and median PFS, 7.4 months (95% CI: 4.2-8.4). Furthermore, the median OS in patients with distant metastasis was 10.1 months, whereas that in patients with locally advanced PDAC was 22.6 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). There were no treatment-related deaths.

Conclusion: SOXIRI is considered a promising and well-tolerated regimen in patients with unresectable PDAC.
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http://dx.doi.org/10.1634/theoncologist.2018-0900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656520PMC
June 2019

Clinicopathological and immunological features of follicular pancreatitis - a distinct disease entity characterised by Th17 activation.

Histopathology 2019 Apr 13;74(5):709-717. Epub 2019 Feb 13.

Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan.

Aim: Follicular pancreatitis is a recently recognised, distinct clinicopathological entity characterised by the presence of many intrapancreatic lymphoid follicles with reactive germinal centres. However, the clinicopathological and immunological features and causes have not yet been established. We assessed the clinicopathological and immunological profiles of patients with follicular pancreatitis who underwent surgery.

Methods And Results: This study included three patients with pancreatic masses (age range = 62-75 years; women:men: 1:2). A histopathological study of the resected pancreatic masses revealed abundant lymphoid follicles with reactive germinal centres in both periductal regions and diffusely within the parenchyma. No storiform fibrosis, obliterative phlebitis or granulocytic epithelial lesions were observed. The immunohistochemical examination revealed an IgG4/IgG-positive plasma cell ratio <30% in all patients. Podoplanin (Th17 marker)-expressing lymphocytes were present in the lymphoid follicles of those with follicular pancreatitis, whereas these were absent in normal lymph nodes and in lymphoid follicles of those with IgG4-related autoimmune pancreatitis (AIP). An RNA digital counting assay clearly demonstrated that the expression counts of 20 genes, including dendritic cells and lymphoid follicles markers, and related cytokines were significantly higher in follicular pancreatitis than in IgG4-related AIP (P < 0.01). The expressions of CCR6 and IL23A, which are genes related to Th17, were high.

Conclusions: This study shows that follicular pancreatitis is a histopathologically and immunologically distinct disease entity of pancreatitis and is characterised by upregulated Th17 expression.
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http://dx.doi.org/10.1111/his.13802DOI Listing
April 2019

Dual-center randomized clinical trial exploring the optimal duration of antimicrobial prophylaxis in patients undergoing pancreaticoduodenectomy following biliary drainage.

Ann Gastroenterol Surg 2018 Nov 17;2(6):442-450. Epub 2018 Sep 17.

Department of Gastroenterological Surgery (Surgery II) Nagoya University Graduate School of Medicine Nagoya Japan.

Objectives: The aim of this dual-center randomized controlled trial was to determine the optimal duration of antimicrobial prophylaxis in patients treated with pancreaticoduodenectomy (PD) who underwent preoperative biliary drainage (PBD) but were without cholangitis.

Background: Some reports showed that PBD in patients undergoing pancreatectomy increased the rate of perioperative complications. However, no clinical trial has evaluated the optimal duration of antimicrobial prophylaxis with a focus on patients who underwent PD following PBD.

Methods: A total of 82 patients who underwent PD between March 2012 and December 2016 were randomly assigned to either a 1-day group (n = 40), in which cefozopran (CZOP) as antimicrobial prophylaxis was given only on the day of surgery, or a 5-day group (n = 42), in which CZOP was given for 5 consecutive days beginning on the day of surgery. We evaluated the incidence of infectious and other complications after PD.

Results: Outcomes were significantly better in the 1-day group compared with the 5-day group ( < 0.05) in terms of the incidence of overall infectious complications (15% vs 36%, respectively), intra-abdominal abscess (3% vs 21%, respectively), clinically relevant postoperative pancreatic fistula (8% vs 24%, respectively), and Clavien-Dindo grade III-V complications (10% vs 31%, respectively). Duration of postoperative hospital stay was significantly shorter in the 1-day group (10 days vs 15 days,  = 0.018). Anaerobic bacteria and methicillin-resistant cocci were isolated from the drainage fluid only among patients in the 5-day group.

Conclusion: Single-day prophylactic use of CZOP is appropriate for patients who undergo PD following PBD without preoperative cholangitis.
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http://dx.doi.org/10.1002/ags3.12209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236101PMC
November 2018

Does modified Blumgart anastomosis without intra-pancreatic ductal stenting reduce post-operative pancreatic fistula after pancreaticojejunostomy?

Asian J Surg 2019 Jan 4;42(1):343-349. Epub 2018 Aug 4.

Department of Surgery, Kansai Medical University, 2-3-1 Shin-machi, Hirakata, Osaka, 573-1191, Japan.

Background: Post-operative pancreatic fistula (POPF) is one of the most common and serious complications after pancreaticoduodenectomy (PD). The aim of this study is to retrospectively compare clinically relevant (CR) POPF and other complications after pacreaticojejunostomy (PJ) after modified Kakita (m-Kakita) or modified Blumgart (m-Blumgart) anastomoses without stenting in a single institution.

Methods: One hundred twenty-eight patients underwent PJ using m-Kakita anastomoses (two interrupted penetrating sutures) between January 2009 and December 2011. One hundred eighteen patients underwent m-Blumgart anastomoses (two transpancreatic/jejunal seromuscular sutures to cover the pancreatic stump with jejunal serosa) between January 2014 and December 2015. Demographics, clinical characteristics, and post-operative mortality and morbidity were retrospectively compared between the two groups.

Results: There were no significant differences in demographics or clinical characteristics between the two groups except operative time. A significantly lower rate of CR-POPF was found in the m-Blumgart group relative to the m-Kakita group (10% vs. 19%, p = 0.038). Univariate and multivariate analyses revealed that the m-Blumgart anastomosis and fistula risk category (Negligible, Low) were independently protective against CR-POPF (p < 0.05).

Conclusion: This retrospective single-center study demonstrated that the modified Blumgart method without pancreatic duct stenting was associated with a lower rate of CR-POPF.
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http://dx.doi.org/10.1016/j.asjsur.2018.06.008DOI Listing
January 2019

High-Throughput Screening for Linear Ubiquitin Chain Assembly Complex (LUBAC) Selective Inhibitors Using Homogenous Time-Resolved Fluorescence (HTRF)-Based Assay System.

SLAS Discov 2018 12 2;23(10):1018-1029. Epub 2018 Aug 2.

1 Biological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka, Japan.

The nuclear factor κB (NF-κB) pathway is critical for regulating immune and inflammatory responses, and uncontrolled NF-κB activation is closely associated with various inflammatory diseases and malignant tumors. The Met1-linked linear ubiquitin chain, which is generated by linear ubiquitin chain assembly complex (LUBAC), is important for regulating NF-κB activation. This process occurs through the linear ubiquitination of NF-κB essential modulator, a regulatory subunit of the canonical inhibitor of the NF-κB kinase complex. In this study, we have established a robust and efficient high-throughput screening (HTS) platform to explore LUBAC inhibitors, which may be used as tool compounds to elucidate the pathophysiological role of LUBAC. The HTS platform consisted of both cell-free and cell-based assays: (1) cell-free LUBAC-mediated linear ubiquitination assay using homogenous time-resolved fluorescence technology and (2) cell-based LUBAC assay using the NF-κB luciferase reporter gene assay. By using the HTS platform, we performed a high-throughput chemical library screen and identified several hit compounds with selectivity against a counterassay. Liquid chromatography-mass spectrometry analysis revealed that these compounds contain a chemically reactive lactone structure, which is transformed to give reactive α,β-unsaturated carbonyl compounds. Further investigation revealed that the reactive group of these compounds is essential for the inhibition of LUBAC activity.
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http://dx.doi.org/10.1177/2472555218793066DOI Listing
December 2018

Use of a piece of free omentum to prevent bile leakage after subtotal cholecystectomy.

Surgery 2018 09 7;164(3):419-423. Epub 2018 Jun 7.

Department of Surgery, Kansai Medical University, Osaka, Japan.

Background: Bile leakage after subtotal cholecystectomy (SC) is clinically serious. To prevent such leakage, we developed a new surgical technique in which a free piece of omentum is plugged into the gallbladder stump (omentum plugging technique). We evaluated whether the omentum plugging technique prevents bile leakage after subtotal cholecystectomy.

Methods: Prospectively collected data of patients who had undergone subtotal cholecystectomy without cystic duct closure in the Department of Surgery of Kansai Medical University during the 12 years from January 2006 to March 2018 were reviewed retrospectively. The outcomes of patients who had undergone subtotal cholecystectomy with the omentum plugging technique (omentum plugging technique group) were compared with those of patients who had undergone subtotal cholecystectomy without the omentum plugging technique (Control group). The outcomes of interest were perioperative data and postoperative complications including bile leakage, necessity for interventions for complications, and duration of hospitalization.

Results: Fifty of 2,447 consecutive patients (2.0%) had undergone subtotal cholecystectomy. Of these 50 patients, 18 were treated with the omentum plugging technique (omentum plugging technique group) and 32 were treated without the omentum plugging technique (Control group). One of 18 patients in the omentum plugging technique group and 14 of 32 in the Control group developed postoperative bile leakage. One postoperative interventional treatment for complications was performed in the omentum plugging technique group and 12 in the Control group. The duration of postoperative hospitalization was less in the omentum plugging technique group.

Conclusion: The omentum plugging technique appears to be an effective operative technique for preventing postoperative bile leakage in selected situations when a "difficult gallbladder" is encountered.
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http://dx.doi.org/10.1016/j.surg.2018.04.022DOI Listing
September 2018

Clinical impact of developing better practices at the institutional level on surgical outcomes after distal pancreatectomy in 1515 patients: Domestic audit of the Japanese Society of Pancreatic Surgery.

Ann Gastroenterol Surg 2018 May 25;2(3):212-219. Epub 2018 Mar 25.

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

Background And Aim: Institutional standardization in the perioperative management of distal pancreatectomy (DP) has not been evaluated in a multicenter setting. The aim of the present study was to assess the influence of institutional standardization on the development of postoperative complications after DP.

Methods: Data were collected from 1515 patients who underwent DP in 2006, 2010, and 2014 at 53 institutions in Japan. A standardized institution (SI) was defined as one that implemented ≥6 of 11 quality initiatives according to departmental policy. There were 541 patients in the SI group and 974 in the non-SI group. Clinical parameters were compared between groups. Risk factors for morbidity and mortality were assessed by logistic regression analysis with a mixed-effects model.

Results: Proportion of patients who underwent DP in SI increased from 16.5% in 2006 to 46.4% in 2014. The SI group experienced an improved process of care and a lower frequency of severe complications vs the non-SI group (grade III/IV Clavien-Dindo; 22% vs 29%, respectively, clinically relevant postoperative pancreatic fistula; 22% vs 31%, respectively, < .05 for both). Duration of in-hospital stay in the SI group was significantly shorter than that in the non-SI group (16 [5-183] vs 20 postoperative days [5-204], respectively; = .002). Multivariate analysis with a mixed-effects model showed that soft pancreas, late drain removal, excess blood loss and long surgical time were risk factors for post-DP complications ( < .05). Pancreatic texture, drain management and surgical factors, but not standardization of care, were associated with a lower incidence of post-DP complications.
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http://dx.doi.org/10.1002/ags3.12066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980579PMC
May 2018

Cytological features of hepatoid adenocarcinoma of the gallbladder: A case report with immunocytochemical analyzes.

Diagn Cytopathol 2018 Aug 10;46(8):711-715. Epub 2018 Apr 10.

Department of Pathology and Laboratory Medicine, Kansai Medical University, Osaka, Japan.

Hepatoid adenocarcinoma is defined as an extrahepatic malignant neoplasm showing morphological and immunohistochemical resemblance of hepatocellular carcinoma. The occurrence of this type of tumor in the gallbladder is extremely rare. In this study, we report the first cytological case of hepatoid adenocarcinoma of the gallbladder. An 80-year-old Japanese female was found to have a tumorous lesion in the gallbladder. Papanicolaou smear of the ascites demonstrated a few epithelial cell clusters composed of round to oval neoplastic cells with distinct cell border and large centrally-located nuclei. Tumor touch smear of the resected tumor revealed the presence of two distinct neoplastic components. The first component was composed of clusters or sheets of epithelial cells with distinct cell border, relatively rich clear cytoplasm, and centrally-located nuclei, as seen in the ascites specimen. The other component was composed of tall columnar cells with large basally-oriented nuclei, and glandular formation was noted as well. Immunocytochemical analyzes of the touch smear material demonstrated that the former component was positive for HepPar1, thus it was considered as a hepatoid adenocarcinoma, and the latter component deemed as a typical adenocarcinoma. Histopathological and immunohistochemical examination of the resected gallbladder tumor confirmed a diagnosis of hepatoid adenocarcinoma. The characteristic cytological features of hepatoid adenocarcinoma are the presence of sheets or clusters of neoplastic cells with distinct cell border and centrally-located nuclei. Immunocytochemical analysis for HepPar1 may help its diagnosis. Demonstration of hepatoid adenocarcinoma is important in the cytological specimen because this type of tumor shows an aggressive clinical course.
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http://dx.doi.org/10.1002/dc.23935DOI Listing
August 2018

Persistent isoflurane-induced hypotension causes hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion.

J Anesth 2018 04 25;32(2):182-188. Epub 2018 Jan 25.

Department of Anesthesiology, Kindai University Faculty of Medicine, 377-2, Ohno-Higashi, Osakasayama, Osaka, 589-8511, Japan.

Background: Postoperative cognitive dysfunction (POCD) is likely to occur in elderly people, who often suffer from cerebral hypoperfusion and white matter lesions even in the absence of cerebral infarctions.

Methods: Thirty-two adult male rats were randomly assigned to one of four groups: the cerebral normoperfusion + normotension group (n = 8), cerebral normoperfusion + hypotension group (n = 8), chronic cerebral hypoperfusion (CCH) + normotension group (n = 8), and CCH + hypotension group (n = 8). A rat model of CCH was developed via the permanent ligation of the bilateral common carotid arteries, but ligation was avoided in the cerebral normoperfusion groups. Two weeks later, the rats were intubated and mechanically ventilated under isoflurane anesthesia, and their mean arterial blood pressure was maintained over 80 mmHg (normotension) or below 60 mmHg (hypotension) for 2 h. After preparing brain slices, histological cresyl violet staining, ionized calcium binding adaptor molecule 1, a marker of microglial activation, or β amyloid precursor protein, a marker of axonal damage, were performed.

Results And Conclusion: CCH per se caused microglial activation and axonal damage, which was not accentuated by hypotension. CCH alone did not cause neuronal damage, but CCH combined with hypotension caused significant neuronal damage in the hippocampal CA1 region. These results suggest that persistent hypotension during general anesthesia might cause neuronal damage in patients with CCH, such as elderly people, and contribute to prevention against POCD.
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http://dx.doi.org/10.1007/s00540-018-2458-zDOI Listing
April 2018

A phase I study for adjuvant chemotherapy of gemcitabine plus S-1 in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1202).

Cancer Chemother Pharmacol 2018 03 5;81(3):461-468. Epub 2018 Jan 5.

Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan.

Purpose: To determine the recommended dose (RD) of gemcitabine (GEM) plus S-1 (GS) in curatively resected biliary tract cancer (BTC) patients without major hepatectomy.

Methods: A standard 3 + 3 dose-escalation design was used with planned dose levels (mg/m) of GEM (administered intravenously on days 1 and 8) and S-1 (administered orally twice daily on days 1-14, with a 1-week rest, every 3 weeks for up to 24 weeks) of 1000/80 (Level 2), 1000/65 (Level 1), 800/65 (Level - 1), and 800/50 (Level - 2).

Results: Thirty-one patients (17 men and 14 women; median age, 70 years) were enrolled. Level 1 was chosen as the starting dose. Three of seven patients developed dose-limiting toxicities at Level 1 and the dose was de-escalated to Level - 1. Five of 12 patients developed Grade 4 neutropenia at Level - 1 and the dose was de-escalated to Level - 2. One patient developed Grade 4 neutropenia at Level - 2. Another patient was unable to receive the day 8 dose due to Grade 3 neutropenia at Level - 2. Level - 1 was confirmed as the maximum tolerated dose and Level - 2 the RD for this regimen. The 1- and 2-year recurrence-free survival rates were 77.0 and 54.0%, respectively. The recurrence-free survival rate of patients in the GS completion group was significantly higher than that of the GS discontinuation group.

Conclusions: Level - 2 was confirmed as the RD (GEM 800 mg/m and S-1 50 mg/m) for GS adjuvant chemotherapy in curatively resected BTC patients without major hepatectomy.
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http://dx.doi.org/10.1007/s00280-017-3513-4DOI Listing
March 2018
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