Search

Hair hormone analysis has received increasing attention in the fields of wildlife management and conservation over the last decade. However, few studies focused on sex steroid hormones, even though hair sex steroid hormone analysis has the potential to provide information on an individual's reproductive health, leading to a better understanding of animal reproductive biology and the assessment of individual and population health. Here, we tested the assay validation and examined whether hair progesterone concentration (HPC) differs between different sexes and age classes in the Asian black bear, Ursus thibetanus. We also investigated the effects of reproductive condition, age, and body condition index (BCI) on HPC to determine the utility of hair progesterone analysis in bears. The assay validation was reported in our study. We found a significantly higher HPC in adult females than in juvenile females and juvenile and adult males. In addition, we found no effects of age and BCI on HPC but a significant positive effect of reproductive condition, as the HPC in breeding adult females was significantly higher than in nonbreeding adult females. These results suggest that hair progesterone analysis has the potential to evaluate the reproductive condition of Asian black bears. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant chemotherapy (AC) for stage III disease is recognized as a standard treatment and is routinely performed in patients with colon cancer (CC). However, the recommendation for AC is mainly based on studies performed in past environments, where D3 lymphadenectomy was not routinely performed., Methods: We retrospectively analyzed CC patients who underwent curative resection with D3 lymphadenectomy in Keio Surveillance Epidemiology and End Results (K-SEER) database. After patients were divided into AC and non-AC groups, propensity score matching (PSM) was performed to match the two groups., Results: After PSM, 84 patients were included in each group. There were no significant differences between the AC and non-AC groups in the 5-year cancer-specific survival (CSS; 88.01% vs. 81.46%, p = 0.295) and 5-year recurrence-free survival (RFS; 69.57 vs. 70.08%, p = 0.820), respectively. In the subgroup analysis, AC improved both the CSS [hazard ratio (HR)0.273; 95% confidence interval (CI) 0.094-0.797, p = 0.017] and RFS (HR 0.376; 95% CI 0.174-0.806, p = 0.012) only for tumors with N2 disease compared to non-AC., Conclusion: The current indications for AC in patients with CC after D3 lymphadenectomy should be reconsidered. It is possible that AC is appropriate only for stage III CC patients with N2 disease., Competing Interests: Declarations Conflict of interest Kiyoaki Sugiura and other co-authors have no conflict of interest., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Despite recent medical advancements, surgery for hilar cholangiocarcinoma is associated with high complication and mortality rates. This may be partly attributed to the absence of established preoperative liver evaluation criteria for safe surgery. This study aimed to propose a reliable indicator for safe and well-planned management of major hepatectomy with extrahepatic bile duct resection., Methods: We included 150 patients who underwent major hepatectomy with extrahepatic bile duct resection between 2013 and 2021 in Japan. The risk factors for post-hepatectomy liver failure (PHLF) were retrospectively analyzed., Results: PHLF was observed in 24 (16.0 %) patients who underwent major hepatectomy with extrahepatic bile duct resection. In the multivariate analysis, the identified risk factors for PHLF were the ratio of future remnant liver volume to total liver volume (FRLV/TLV) ≤ 42 % and indocyanine green clearance fraction of the future remnant liver (ICGK-F) ≤ 0.07. Patients with these two factors were significantly associated with PHLF compared with those with either one or none of the risk factors (60.0 % vs 15.1 % and 8.1 %, respectively)., Conclusion: The combinational use of ICGK-F and FRLV/TLV is useful for preoperative liver function assessment with a safety margin to avoid PHLF and postoperative mortality in hepatectomy for hilar cholangiocarcinoma., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background/purpose: Laparoscopic resection of gallbladder carcinomas remains controversial. This study aimed to evaluate the surgical and oncological outcomes of laparoscopic procedures for suspected gallbladder carcinoma (GBC)., Methods: In this retrospective study, data regarding suspected GBC treated with laparoscopic radical cholecystectomy before 2020 in Japan, was included. Patient characteristics, surgical procedure details, surgical outcomes, and long-term outcomes were analyzed., Results: Data of 129 patients with suspected GBC who underwent laparoscopic radical cholecystectomy were retrospectively collected from 11 institutions in Japan. Among them, 82 patients with pathological GBC were included in the study. Laparoscopic gallbladder bed resection was performed in 114 patients and laparoscopic resection of segments IVb and V was performed in 15 patients. The median operation time was 269 min (range: 83-725 min), and the median intraoperative blood loss was 30 mL (range: 0-950 mL). The conversion and postoperative complication rates were 8% and 2%, respectively. During the follow-up period, the 5-year overall survival rate was 79% and the 5-year disease-free survival rate was 87%. Recurrence was detected in the liver, lymph nodes, and other local tissues., Conclusion: Laparoscopic radical cholecystectomy is a treatment option with potential favorable outcomes in selected patients with suspected GBC., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objective: The immune checkpoint inhibitor pembrolizumab has recently been recognized as a standard treatment regimen for patients with metastatic colorectal cancer and the microsatellite-instability-high/mismatch repair-deficient mutation. However, its cost-effectiveness in late-line treatment remains unclear. The aim of this study was to assess the cost-effectiveness of pembrolizumab for patients with microsatellite-instability-high/mismatch repair-deficient metastatic colorectal cancer., Methods: Markov decision modeling using treatment costs, disease-free survival and overall survival was performed to examine the cost-effectiveness of pembrolizumab monotherapy compared with chemotherapy, and best supportive care. The Japanese healthcare payer's perspective was adopted. The outcomes were modeled on the basis of published literature. The primary outcome was the incremental cost-effectiveness ratio between the strategies. Sensitivity analyses were performed and the effects of uncertainty on the model parameters were investigated., Results: Pembrolizumab monotherapy had incremental cost-effectiveness ratios of $408204.3 per quality-adjusted life-year gained compared with best supportive care and $489123.4 per quality-adjusted life-year gained compared with chemotherapy. Given a Japanese willingness-to-pay threshold of $69560.38 per quality-adjusted life-year, the base case results suggested that pembrolizumab monotherapy was not cost-effective. The sensitivity analysis results were in line with the base case results., Conclusion: Pembrolizumab monotherapy is not a cost-effective option in late-line treatment for patients with metastatic colorectal cancer and microsatellite-instability-high/mismatch repair-deficient mutation in the Japanese healthcare system. Further studies on its cost-effectiveness in first-line treatment are warranted., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

This study assessed drug use patterns among men who have sex with men (MSM) in Japan, and evaluated their potential associations with sexual risk behaviours. Between September and October 2016, study subjects were recruited through a cross-sectional survey (LASH: Love Life and Sexual Health) using a geosocial networking application for MSM. Of the participants, 25.4% (1756/6921) reported ever having used drugs, and 11.3% (780/6921) reported having done so in the past six months. Those who used drugs were more likely to have greater knowledge of HIV/sexually transmitted infections (STIs). Drug use in the past six months was independently associated with each of the following sexual risk behaviours in the same period: (i) six or more sexual partners (adjusted odds ratio [aOR] = 2.70, 95% confidence interval [CI]: 2.30-3.17); (ii) condomless anal intercourse (aOR = 2.88, 95% CI: 2.43-3.42); (iii) group sex (aOR = 2.60, 95% CI: 2.22-3.05); and (iv) sex work (aOR = 2.30, 95% CI: 1.67-3.16). These results suggest that MSM in Japan who use drugs are more likely to report sexual risk behaviours, while also having greater knowledge of HIV/STIs. Supporting MSM to minimise the harm from drug use may be helpful in reducing HIV transmission among this priority population.

People living with HIV (PLWH) are forced to live with multiple and severe stressors. Focusing on sense of coherence (SOC), which is a concept of salutogenic and stress coping capacity, is useful in PLWH support. This study aimed to examine the association between SOC and socioeconomic status (SES) for Japanese PLWH. Methods: This study used data from the HIV Futures Japan national survey, which is an online survey with a cross-sectional design. This survey of PLWH in Japan was conducted from July 2013 to February 2014 and December 2016 to July 2017, resulting in 1422 valid responses. The mean age (SD) was 38.6 years (8.3). The 13-item SOC scale score was divided into two groups, based on Japanese standard score in a previous study, and logistic regression analysis was performed. Results: Education levels were indirectly associated with SOC through occupation. Compared to freelance-profession/self-employed, “unemployed job seekers” (OR [95%CI] = 2.16 [1.16, 4.04]) and “homemaker/recuperating/student” (2.09 [1.09, 4.02]) were directly related to poor SOC, regardless of income. Also, there is a clear SOC disparity in income (compared to “>8 million yen/year”, “<1 million yen/year” was 2.94 [1.46, 5.92], and “1−2.99 million yen/year” was 2.49 [1.33, 4.68]). Conclusion: It became clear that there is a relationship between SOC and SES. The results of this research provide important evidence for health promotion measures for PLWH.

BACKGROUND Infectious complications after solid organ transplantation can be fatal, and early diagnosis and intervention are important. To the best of our knowledge, no study has examined the diagnostic utility of presepsin, a known accurate biomarker, for infectious complications after liver transplantation. This study aimed to evaluate the utility of presepsin for detecting infection and perioperative kinetics of presepsin after liver transplantation. MATERIAL AND METHODS This single-institutional prospective, observational study included 13 patients who underwent living-donor or deceased-donor liver transplantation. Perioperative serum presepsin level was measured 6 times within a week to evaluate its association with infectious complications and compare it with procalcitonin and C-reactive protein levels and leukocyte count. Postoperatively, patients were followed up for 15 days for infectious complications. RESULTS Five of the 13 patients developed infectious complications after liver transplantation. The median time for infection diagnosis was 9 postoperative days (25th-75th percentile, 7-10). Presepsin levels on 5 and 7 postoperative days were significantly higher in patients with infection than in those without (P=0.019 and P=0.011, respectively). In receiver operating characteristic analysis, area under the curve values of presepsin on 5 and 7 postoperative days (0.881 and 0.905, respectively) were higher than those of other biomarkers. The optimal cut-off value of presepsin was 1361 pg/mL on postoperative day 5 and 1375 pg/mL on postoperative day 7. CONCLUSIONS Although this study included a small number of patients, presepsin levels on postoperative days 5 and 7 may be useful indicators for infectious complications after liver transplantation.

Background: The management of complicated appendicitis remains controversial, since this disease has various clinical presentations and is associated with high rates of adverse events. Although initial nonoperative treatment is generally employed for complicated appendicitis, its clinical presentation and the predictors of nonoperative treatment failure are unclear., Methods: Patients diagnosed with complicated appendicitis in our hospital between April 2015 and March 2020 were enrolled. In total, 113 patients were classified into three categories: emergency appendectomy, failure of nonoperative treatment and successful nonoperative treatment. The primary outcome was the rate of failure of nonoperative treatment, as assessed by logistic regression analysis. The secondary outcomes were the operative procedures and postoperative courses of the three groups., Results: Of 113 patients, 45 (40%) underwent emergency appendectomy, 25 (22%) failed nonoperative treatment, and 43 (38%) had successful nonoperative treatment. Among these successful cases, 38 patients (88%) underwent interval appendectomy. In multivariate analyses, the presence of a fecalith in the proximal area of the appendix was an independent risk factor for failure of nonoperative treatment (odds ratio, 20.5; 95% confidence interval, 4.37-95.7, P < 0.001). Postoperative outcomes were more unfavorable in cases of failed nonoperative treatment than in cases of emergency and interval appendectomy., Conclusions: The presence of a fecalith in the proximal area of the appendix is an independent predictor for failure of nonoperative treatment for complicated appendicitis in adults. Patients with this risk factor should be considered candidates for surgical treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Despite the increasing number of laparoscopic liver resection (LLR) procedures, postoperative bile leakage (POBL) remains a major complication. We occasionally experienced intraoperative bile leakage (IOBL) during LLR and managed it within the restrictions of laparoscopic surgery. However, there have been no reports about IOBL in LLR. We therefore investigated the impact of IOBL on postoperative outcomes and its predictive factors., Methods: We reviewed 137 patients who underwent LLR from April 2016 to March 2019 at our institute and assigned them to IOBL-positive or IOBL-negative groups. We compared clinicopathological characteristics and perioperative outcomes. Patients were further divided into four groups according to IOBL pattern, and the frequency of POBL in each was calculated. Predictors of IOBL were identified using multivariate logistic regression analysis., Results: There were 30 and 107 patients in the IOBL-positive and IOBL-negative groups, respectively. In the IOBL-positive group, operative time and postoperative hospital stays were significantly longer (P < 0.001). The frequency of POBL was significantly higher in the IOBL-positive group (P = 0.006). The IOBL-positive group was divided into two subgroups: IOBL from the transected parenchyma (IOBL-TP, n = 18) and from the main Glissonean pedicle (IOBL-mGP, n = 12). The IOBL-negative group was divided into two subgroups: bile staining in the mGP (BS-mGP, n = 9) and no change (NC, n = 98). POBL occurred in 11% (n = 2/18) of patients with IOBL-TP, 25% (n = 3/12) of those with IOBL-mGP, 11% (n = 1/9) of those with BS-mGP, and 1% (n = 1/98) of those with NC. Age, diabetes mellitus, indocyanine green retention rate, and Glissonean approach were predictors of IOBL (P < 0.05)., Conclusions: IOBL was relatively common during LLR and resulted in a higher incidence of POBL. Depending on the predictive factors, IOBL must be promptly identified and appropriately managed.

Background: Pancreatic fistulas remain a significant concern after pancreatectomy owing to the associated high risk of mortality and high costs. It is not possible to perform preoperative risk stratification for all patients. This study aimed to evaluate the usefulness of the measurement of portal vein (PV) distance as a predictive indicator of pancreatic fistula development after pancreatoduodenectomy and compare it with the usefulness of other indicators such as body mass index (BMI), and abdominal fat area., Methods: Patient characteristics, preoperative laboratory data, radiographic findings, and their association with pancreatic fistula development after pancreatoduodenectomy were analyzed for 157 patients who underwent resection during 2011-2017. Clinically relevant postoperative pancreatic fistulas (CR-POPF) were defined as Grade B or C fistulas based on the International Study Group of Pancreatic Surgery (ISGPS) 2016 consensus., Results: CR-POPF developed in 38 patients (24.2%). Multivariate logistic regression indicated that PV distance and BMI were potential candidates for predictive models for pancreatic fistula development, and small pancreatic duct diameter, diabetes mellitus development, and pathology of non-pancreatic cancers were independent factors for CR-POPF. When comparing the two risk models (PV distance- and BMI-based models), the PV distance-derived risk model was compatible to the BMI-based stratification models (area under the curve 0.831 vs. 0.830)., Conclusions: PV distance was confirmed to be a useful risk predictor for CR-POPF. This research highlighted the efficacy of abdominal thickness measurement, which is simple and easily applicable in the clinical setting.

The selective arterial calcium injection (SACI) test is useful for patients with functional pancreatic neuroendocrine tumors (F-PNETs). This study evaluated which patients with F-PNETs would benefit from the SACI test. We retrospectively analyzed the preoperative findings of patients on computed tomography (CT), magnetic resonance imaging (MRI), CT angiography (CTA), and the SACI test. Fourteen patients who underwent pancreatectomy between January 1997 and September 2016 for F-PNETs were evaluated. We classified these patients into groups A, B, and C; group A, one tumor detected by either CT or MRI; group B, multiple tumors detected; and group C, the tumor location was accordant on CT, MRI, and CTA, but the SACI test revealed another tumor. In group A, the tumor was also detected by CTA and the SACI test was positive on calcium injection. In group B, the focus tumor among the multiple tumors was detected by the SACI test. In group C, another tumor was identified by the SACI test, whose location was different from that detected using CT and MRI. The SACI test is more useful for multiple F-PNETs on CT or MRI. If CT or MRI detects a single tumor, the SACI test or CTA may be unnecessary.

Background: Although the rates of surgical site infection are decreasing, surgical site infection after pancreatectomy remains frequent because of postoperative pancreatic fistula. Recent studies suggested a relationship between postoperative pancreatic fistula and pathogens cultured from drainage fluids after pancreatectomy. This study aimed to assess and evaluate high-risk pathogens cultured from postoperative drainage fluids for postoperative pancreatic fistulas or severe postoperative complications after pancreatectomy., Materials and Methods: We retrospectively enrolled patients who underwent pancreaticoduodenectomy or distal pancreatectomy between 2012 and 2019. We assessed clinical characteristics and microbiological results of drainage cultures of pancreaticoduodenectomy or distal pancreatectomy patients, and we investigated the risk factors for clinically relevant postoperative pancreatic fistulas and Clavien-Dindo status using univariate and multivariate analyses. Finally, we detected high-risk pathogens from drainage cultures and analyzed the correlation between these pathogens and the severity of clinically relevant postoperative pancreatic fistula or Clavien-Dindo status., Results: Four hundred and twenty-nine patients were enrolled: 257 underwent pancreaticoduodenectomy and 172 underwent distal pancreatectomy. Clinically relevant postoperative pancreatic fistulas and Clavien-Dindo status ≥ III were more frequently seen in pancreaticoduodenectomy patients than in distal pancreatectomy patients, namely grade C postoperative pancreatic fistula, which was observed in 19 pancreaticoduodenectomy patients. The most common pathogen found from drainage cultures was Enterococcus species, followed by Enterobacter species and Candida species. All pathogens were associated with clinically relevant postoperative pancreatic fistulas; however, Candida species was a dominant microorganism of clinically relevant postoperative pancreatic fistulas grade C, Clavien-Dindo status ≥ IV, and hemorrhage due to pseudoaneurysm., Conclusion: The presence of Candida species in the drainage fluid culture after pancreaticoduodenectomy can be a predictive factor of severe infectious complications, including postoperative pancreatic fistulas; thus, we should regularly collect cultures from drainage fluids and monitor for Candida infection., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O -glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA- or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O -glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

Background: Synovial sarcoma is a soft tissue malignancy that frequently affects the extremities, adjacent to the large joints. Synovial sarcoma has a high rate of distant metastasis; however, pancreatic metastasis is extremely rare, and to our knowledge, there has been no report of bleeding due to spontaneous tumor rupture. This study reports the case of a patient with synovial sarcoma pancreatic metastasis causing tumor rupture and bleeding, which was successfully managed with emergent distal pancreatectomy., Case Presentation: A 27-year-old woman underwent extensive resection of the primary tumor and partial lung resection after chemotherapy for left femoral synovial sarcoma and multiple lung metastases 4 years prior. During the follow-up, a 35-mm tumor was noted in the pancreatic tail on abdominal computed tomography (CT), and no other distant metastases were detected via positron emission tomography CT. Laparoscopic distal pancreatectomy was scheduled for pancreatic metastasis of synovial sarcoma. However, before the scheduled pancreatectomy could be conducted, the patient visited the emergency department because of abdominal pain that occurred after consuming a small amount of alcohol, and CT showed ascites with high CT values and leakage of contrast media. She was diagnosed with intra-abdominal hemorrhage due to a ruptured metastatic pancreatic tumor, and an emergency operation was performed. In total, 1500 mL of blood was evacuated from the abdomen, and the bleeding pancreatic tail tumor was resected. Histopathological findings revealed synovial sarcoma metastasis and a ruptured tumor capsule, and tumor cells were observed in the hematoma. After discharge on postoperative day 18, the patient was carefully monitored and confirmed to be in relapse-free survival, without chemotherapy, at 6 months post-surgery., Conclusions: While the rate of tumor growth varies depending on the grade of the tumor, the possibility of rupture should be considered even in metastatic pancreatic tumors. In the case of pancreatic tumor rupture with stable circulation, radiological evaluation for oncology is necessary, and primary resection may be compatible with resectable cases.

Background: Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial., Methods: The inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m 2 /day orally twice daily on days 1-28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS)., Results: Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events., Conclusions: One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing., Trial Registration: UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000009347.

Formalin-fixed paraffin-embedded (FFPE) tissues used for routine pathological diagnosis are valuable for cancer genomic analysis; however, the association between mutation status derived from these specimens and prognosis in pancreatic ductal adenocarcinoma (PDAC) remains unclear. We analyzed 50 cancer-related gene mutations including driver genes in PDAC, using next-generation sequencing (NGS) to clarify the association between gene mutations and prognosis. DNA was extracted from FFPE tissues obtained from 74 patients with untreated resectable PDAC who underwent surgery at our institution between 2013 and 2018. Fifty of the 74 patients with DNA extracts from FFPE samples suitable for NGS were analyzed. The prevalence of driver gene mutations was as follows: 84% for KRAS, 62% for TP53, 32% for SMAD4, and 18% for CDKN2A. There were no cases of single SMAD4 mutations; its rate of coincidence with KRAS or TP53 mutations was 30% and 2%, respectively. The combination of KRAS and SMAD4 mutations resulted in significantly shorter relapse-free survival (RFS; median survival time [MST], 12.3 vs. 28.9 months, P = .014) and overall survival (OS; MST, 22.3 months vs. not reached, P = .048). On multivariate analysis, the combination of KRAS and SMAD4 mutations was an independent prognostic factor for RFS (hazard ratio [HR] 4.218; 95% confidence interval [CI], 1.77-10.08; P = .001) and OS (HR 6.730; 95% CI, 1.93-23.43; P = .003). The combination of KRAS and SMAD4 mutations in DNA obtained from FFPE tissues is an independent poor prognostic factor in PDAC., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The Response Evaluation Criteria in Solid Tumors (RECIST) for computed tomography (CT) is preoperatively used to evaluate therapeutic effects. However, it does not reflect the pathological treatment response (PTR) of pancreatic ductal adenocarcinoma (PDAC). The Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) for positron emission tomography (PET)/CT is effective in other cancers. This study aimed to confirm the usefulness of PERCIST and the prognostic utility of PET/CT for PDAC., Methods: Forty-two consecutive patients with PDAC who underwent neoadjuvant therapy (NAT) and pancreatectomy at our institution between 2014 and 2018 were retrospectively analyzed. We evaluated the treatment response and prognostic significance of PET/CT parameters and other clinicopathological factors., Results: Twenty-two patients who underwent PET/CT both before and after NAT with the same protocol were included. RECIST revealed stable disease and partial response in 20 and 2 cases, respectively. PERCIST revealed stable metabolic disease, partial metabolic response, and complete metabolic response in 8, 9, and 5 cases, respectively. The PTR was G3, G2, and G1 in 8, 12, and 2 cases, respectively. For comparing the concordance rates between PTR and each parameter, PERCIST (72.7% [16/22]) was significantly superior to RECIST (36.4% [8/22]) (P = .017). The area under the curve survival values of PET/CT parameters were 0.777 for metabolic tumor volume (MTV), 0.500 for maximum standardized uptake value, 0.554 for peak standardized uptake value corrected for lean body mass, and 0.634 for total lesion glycolysis. A 50% cut-off value for the MTV reduction rate yielded the largest difference in survival between responders and nonresponders. On multivariate analysis, MTV reduction rates < 50% were independent predictors for relapse-free survival (hazard ratio [HR], 3.92; P = .044) and overall survival (HR, 14.08; P = .023)., Conclusions: PERCIST was more accurate in determining NAT's therapeutic effects for PDAC than RECIST. MTV reduction rates were independent prognostic factors for PDAC., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Technological innovations have made it possible to use laparoscopic liver resection in cases with pre-existing adhesions or cicatricial changes. However, laparoscopic repeat liver resection (LRLR) still represents a challenge for surgeons, especially in case of previous open liver surgery. This study evaluated the outcomes of LRLR after open liver resection (OLR) in cases of recurrent liver cancer., Materials and Methods: A total of 62 patients who underwent laparoscopic minor liver resection at our institution between September 2012 and September 2016 were retrospectively divided into an LRLR group (n = 13) and a laparoscopic primary liver resection group (LPLR; n = 49). The two groups were compared in terms of patient demographics, surgical procedures and short-term outcomes. Recurrence-free survival (RFS) and overall survival (OS) were compared for patients with hepatocellular carcinoma (HCC) or colorectal liver metastases (CRLMs)., Results: There was a significant intergroup difference in the hepatitis virus background, although the two groups' primary histology and pre-operative liver function were comparable. The two groups had statistically similar values for extent of resection, operative time, estimated blood loss, transfusion requirement, conversion to laparotomy, post-operative complications, surgical margins, time to oral intake and hospital stay. No significant differences were detected when we stratified the cases according to low and intermediate difficulty. Furthermore, there were no intergroup differences in RFS or OS in the two groups for patients with HCC and CRLM., Conclusions: The findings suggest that minor LRLR after OLR is safe and comparable with minor LPLR in the present study., Competing Interests: None

Background: Bloodstream infection (BSI) is a life-threatening complication after living donor liver transplantation (LDLT). We aimed to explore the incidence and predisposing factors of BSI at our institution., Methods: We conducted a retrospective cohort analysis on all consecutive adults with BSI within 6 months after LDLT performed between 2005 and 2016. For antimicrobial prophylaxis, ampicillin/sulbactam, cefotaxime, and micafungin were administered. From 2011, methicillin-resistant Staphylococcus aureus (MRSA) carriers were decolonized using mupirocin ointment and chlorhexidine gluconate soap. Risk factors for BSI were identified by uni- and multivariate logistic regression., Results: Of a total of 106 LDLTs, 42 recipients (40%) suffered BSI. The BSI group demonstrated significantly higher in-hospital mortality rates compared with the non-BSI group (24% vs. 7%, P = .01). We identified MRSA carrier (odds ratio [OR], 19.1; P < .001), ABO incompatibility (OR, 2.9; P = .03), and estimated glomerular filtration rate <30 mL/min/1.73m 2 (OR, 15.8; P = .02) as independent risk factors for BSI. Decolonization treatment for MRSA carriers did not reduce the incidence of all-cause BSI but reduced the frequency of BSI caused by MRSA., Conclusion: To our knowledge, for the first time, MRSA carriers were revealed to be highly vulnerable to BSI after LDLT., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of the present study was to investigate the clinicopathological features and prognostic factors associated with pre- and postoperative serum albumin levels in patients with curatively resected pancreatic ductal adenocarcinoma (PDAC). To achieve this, the data of patients who underwent pancreatectomy for PDAC between January 1995 and March 2016 were retrospectively reviewed, and the pre- and postoperative serum albumin levels at postoperative months (POMs) 3, 6, and 12 were evaluated. The serum albumin recovery rate was also investigated. A total of 196 patients were enrolled in the present study. In the multivariate Cox regression analysis, lymph node metastasis [hazard ratio (HR): 1.65; P=0.022], serum albumin level at POM 12 (≥3.9 g/dl; HR: 0.60; P=0.017), and serum albumin recovery rate at POM 12 (≥1.00; HR: 0.60; P=0.017) were independent prognostic factors for disease-free survival. Lymph node metastasis (HR: 1.79; P=0.013) and serum albumin level at POM 12 (≥3.9 g/dl) (HR: 0.60; P=0.033) were independent prognostic factors for overall survival. These results indicated that the postoperative level and recovery rate of serum albumin are potential biomarkers for predicting the prognosis of patients with curatively resected PDAC. However, further studies are required in order to investigate the survival benefit of increasing postoperative serum albumin levels in these patients.

Background: We aimed to evaluate the efficacy and safety of 5-fluorouracil-based neoadjuvant chemoradiotherapy (NACRT) in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma (PDAC)., Methods: This retrospective study investigated the clinicopathological features and > 5-year survival of patients with T3/T4 PDAC who underwent NACRT at our institute between 2003 and 2012., Results: Seventeen resectable and eight borderline resectable patients were included. The protocol treatment completion and resection rates were 92.0% and 68.0%, respectively. Two patients failed to complete chemotherapy owing to cholangitis or anorexia. Common grade 3 toxicities included anorexia (12%), neutropenia (4%), thrombocytopenia (4%), anemia (4%), and leukopenia (12%). Pathologically negative margins were achieved in 94.1% of patients who underwent pancreatectomy. Pathological response according to Evans' classification was grade IIA in 10 patients (58.8%), IIB in 5 patients (29.4%), and IV in 2 patients (11.8%). Postoperative pancreatic fistulas were observed in four patients (23.5%), delayed gastric emptying in one patient (5.9%), and other operative morbidities in four patients (23.5%). The 1-, 2-, 5-, and 10-year overall survival rates were 73.9%, 60.9%, 60.9%, and 39.1%, respectively (median follow-up period, 80.3 months)., Conclusions: NACRT is tolerable and beneficial for resectable/borderline resectable PDAC, even in the long-term.

Background: During minimally invasive surgery, efficient and nontoxic hemostats are important for difficult to access bleeding areas. Polylactic acid is an ecofriendly hemostatic agent and we aimed to evaluate the efficacy of a polylactic acid nonwoven fabric (PLAF) developed by Toray Industries, Inc, on liver hemostasis in a preclinical study., Materials and Methods: PLAF consists of both 1-µm diameter fibers and 100-µm diameter beaded fibers. Four rats were used, and 2 trough-shaped resections of the liver parenchyma were performed (n = 8 lobes). Immediately after the resection, PLAF (PLAF group: n = 4 lobes) or rayon gauze (Rayon group: n = 4 lobes) were applied on the resected plane and compressed manually. We compared the mean time to hemostasis and blood loss per lobe, as well as histological findings between the groups., Results: The PLAF group had a significantly shorter bleeding time ( P = .006), and showed lower blood loss compared with the Rayon group ( P = .076). Histopathological evaluation showed a large amount of beads on the liver surface in the PLAF group. Aggregated red blood cells evident by electron microscopy and von Willebrand factor immunofluorescence were seen surrounding the beads. The PLAF group showed significantly greater von Willebrand factor expression than the Rayon group ( P = .004)., Discussion: This new PLAF showed superior outcomes thanks to its unique characteristic of forming beaded nanofibers, and it has the potential to be an efficient hemostat in minimally invasive surgery in the human body.

Background: Although various devices have been clinically used for laparoscopic liver resection (LLR), the best device for liver parenchymal transection remains unknown. Olympus Corp (Tokyo, Japan) developed a laparoscopic hybrid pencil (LHP) device, which is the first electric knife to combine ultrasound and electric energy with a monopolar output. We aimed to evaluate the feasibility of using the LHP device and to compare it with the laparoscopic monopolar pencil (LMP) and laparoscopic ultrasonic shears (LUS) devices for LLR in a porcine model., Methods: Nine male piglets underwent laparoscopic liver lobe transections using each device. The operative parameters were evaluated in the 3 groups (n = 24 lobes) during the acute study period. The imaging findings from contrast-enhanced computed tomography and histopathological findings of autopsy on postoperative day 7 were compared among groups (n = 6 piglets) during the long-term study., Results: The transection time was shorter ( P = .001); there was less blood loss ( P = .018); and tip cleaning ( P < .001) and instrument changes were less often required ( P < .001) in the LHP group than in the LMP group. The LHP group had fewer instances of bleeding ( P < .001) and coagulator usage ( P < .001) than did the LUS group. In the long-term study, no postoperative adverse events occurred in the 3 groups. The thermal spread and depth of the LHP device were equivalent to those of the LMP and LUS devices (vs LMP: P = .226 and .159; vs LUS: P = 1.000 and .574)., Conclusions: The LHP device may be an efficient device for LLR if it can be applied to human surgery.

Introduction: The prevalence of surgical site infection (SSI) remains higher in gastrointestinal surgery than in other surgeries. Although several guidelines have indicated the efficacy of chlorhexidine and povidone-iodine in reducing the SSI rate, the optimal recommendation has still not been established. Therefore, it is necessary to determine the more effective antiseptic for surgical site preparation. Olanexidine (1.5% olanedine, Otsuka Pharmaceutical Factory, Tokushima, Japan), which is a new antiseptic in Japan, has antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria. Our study will contribute to determining a new antiseptic for use in gastrointestinal and other surgeries., Methods and Analysis: We propose a multicentre, randomised controlled clinical trial for comparing two treatments, that is, 1.5% olanexidine or 10% povidone-iodine, for surgical skin preparation to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. Patients aged ≥20 years at the time of consent will be included. The primary outcome measure is the 30-day postoperative SSI rate. For the primary analysis, which is aimed at comparing the treatment effects, the adjusted risk ratio and its 95% CI will be estimated using the Mantel-Haenszel method., Ethics and Dissemination: The protocol was first approved by the Institutional Review Board of Keio University School of Medicine, followed by the institutional review board of each participating site. Participant recruitment began in June 2018. The final results will be published in international peer-reviewed medical journals., Trial Registration Number: UMIN 000031560; Pre-results., Competing Interests: Competing interests: YK received grant support from Otsuka Pharmaceutical Factory Inc., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cytomegalovirus (CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia (AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation (LDLT)., Case Summary: The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy (GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE., Conclusion: This case report suggests a monitoring method that could be useful for AG-negative CMV gastroenteritis after a solid-organ transplantation., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest.

Background: Oesophageal cancer has a high metastatic potential and poor prognosis, with a significant risk of recurrence after radical resection. However, resected pancreatic metastasis from oesophageal cancer is rare., Case Presentation: Eleven years prior, a seventy-year-old woman had been treated with transthoracic radical oesophagectomy for oesophageal squamous cell carcinoma. Four years prior, she had undergone chemotherapy for lymph node recurrence at the splenic hilum and achieved a partial response. She had also received chemoradiotherapy for lymph node recurrence at the splenic hilum 3 years prior; a complete response was achieved. However, routine follow-up with abdominal computed tomography recently revealed a tumour at the pancreatic tail and swollen lymph nodes. The patient underwent distal pancreatectomy on the basis of a pre-operative diagnosis of primary pancreatic cancer, although a histological examination of the surgical specimen revealed metastatic squamous cell carcinoma that was compatible with metachronous pancreatic metastasis from oesophageal squamous cell carcinoma. The patient has been undergoing clinical follow-up without adjuvant therapy and has been disease-free for 24 months after resection of the pancreatic metastasis., Conclusions: Resection of pancreatic metastasis may improve prognosis and should be considered when treating patients with solitary metastasis from oesophageal squamous cell carcinoma.

Nutritional support after pylorus-preserving pancreaticoduodenectomy (PpPD) is still controversial. This study aimed to evaluate the efficacy of enteral nutrition (EN) via the double elementary diet (W-ED) tube after PpPD. One hundred two patients who received EN by the W-ED tube were compared with 52 patients who received total parental nutrition (TPN) previously. Clinicopathological and postoperative features were analyzed among the two groups. Patients with EN by the W-ED tube after PpPD had a lower incidence of postoperative pancreatic fistula than those with TPN. The total protein and albumin levels on discharge in the EN group were significantly higher than those in the TPN group. In the case without complication, decreasing rate of the third lumbar vertebra skeletal muscle area was significantly lower in the EN group. In the cases of soft pancreas, drainage volume by the W-ED tube until four postoperative day was significantly larger in the case without postoperative pancreatic fistula. The W-ED tube offers the advantages of reducing gastrointestinal pressure and enabling reduction of complications after PpPD surgery.

Background: Various approaches to hepatectomy have been proposed for cT2 gallbladder cancers (GBC), but the optimal management strategy remains unclear. The aim of this study is to assess the effectiveness of using an indocyanine green (ICG)-based intraoperative navigation system during hepatic resection for cT2 GBC., Methods: From September 2007 to December 2017, 24 consecutive patients diagnosed with cT2 GBC underwent hepatic resection using ICG navigation. After cannulation of the cholecystic artery, ICG diluted with dissolution liquid was injected and ICG fluorescence illumination was visualized with the HyperEye Medical System. And additional histopathological examination was performed on the most recent 15 of the 24 patients for detection of microscopic liver metastasis., Results: For all patients, the disease-free survival rate was 59.1% at 5 years and overall survival rate was 86.2% at 5 years. Microscopic liver metastasis was detected in the resected liver in 3 (20%) of 15 patients, whose site of liver was S6, S5, and S5, respectively. The weight of the liver resected using ICG navigation was significantly smaller than that of S4a/S5 segmentectomy (P < 0.0001)., Conclusion: Resected hepatic lesion using ICG imaging was possible to perform hepatectomy including liver micro-metastasis without excess or deficiency. This procedure might be novel intraoperative imaging method to provide valuable information on the optimal surgical approach to cT2 GBC.

Expression of 14q32-encoded miRNAs is a favorable prognostic factor in patients with metastatic cancer. In this study, we used genomic inhibition of DNA methylation through disruption of DNA methyltransferases DNMT1 and DNMT3B and pharmacologic inhibition with 5-Aza-2'-deoxycytidine (5-Aza-dC, decitabine) to demonstrate that DNA methylation predominantly regulates expression of metastasis-suppressive miRNAs in the 14q32 cluster. DNA demethylation facilitated CCCTC-binding factor (CTCF) recruitment to the maternally expressed gene 3 differentially methylated region (MEG3-DMR), which acts as a cis -regulatory element for 14q32 miRNA expression. 5-Aza-dC activated demethylation of the MEG3-DMR and expression of 14q32 miRNAs, which suppressed adhesion, invasion, and migration (AIM) properties of metastatic tumor cells. Cancer cells with MEG3-DMR hypomethylation exhibited constitutive expression of 14q32 miRNAs and resistance to 5-Aza-dC-induced suppression of AIM. Expression of methylation-dependent 14q32 miRNAs suppressed metastatic colonization in preclinical models of lung and liver metastasis and correlated with improved clinical outcomes in patients with metastatic cancer. These findings implicate epigenetic modification via DNA methylation in the regulation of metastatic propensity through miRNA networks and identify a previously unrecognized action of decitabine on the activation of metastasis-suppressive miRNAs. SIGNIFICANCE: This study investigates epigenetic regulation of metastasis-suppressive miRNAs and the effect on metastasis., (©2018 American Association for Cancer Research.)

Background: Since the concept of intraductal tubulopapillary neoplasm (ITPN) was introduced in the current World Health Organization classification of tumors, the number of reports of ITPN occurrence has increased gradually. However, ITPN is usually located in the main pancreatic duct, with few reports of a branch duct ITPN. As a result, imaging protocols for the diagnosis of a branch duct ITPN have not been established., Case Presentation: We report a case of a concurrent presentation of a branch duct ITPN and intraductal papillary mucinous neoplasm (IPMN) in the head of the pancreas, with a superior mesenteric artery (SMA) aneurysm. Initially, the cystic masses in the pancreatic head were diagnosed as branch duct IPMNs, with treatment consisting of a pylorus-preserving pancreaticoduodenectomy, in combination with an aneurysmectomy performed for treatment of the SMA aneurysm. Pathological examination confirmed these cysts were a combination of branch-type ITPN and IPMN. The patient recovered from the treatment without complication, with no evidence of recurrence over a period of 34 months post-surgery., Conclusion: This case report of a synchronous presentation of an ITPN and IPMN indicates the difficulty in differentiating these two types of neoplasms in the branch duct of the pancreatic head.

Background: High-mobility-group box chromosomal protein 1 has been identified as an important mediator of various kinds of acute and chronic inflammation. In this study, we aimed to develop a column that effectively adsorbs high-mobility-group box chromosomal protein 1 by altering the pore size of the fiber., Materials and Methods: First, we produced three types of porous polymethylmethacrylate fiber by altering the concentration of polymethylmethacrylate dissolved in dimethylsulfoxide. We then selected a fiber based on the results of an in vitro incubation test of high-mobility-group box chromosomal protein 1 adsorption. Using the selected fiber, we constructed a new column and tested its high-mobility-group box chromosomal protein 1 adsorption capacity during 4-h extracorporeal hemoperfusion in a swine acute liver failure model., Results: Electron microscope observation showed that the three types of fibers had different pore sizes on the surface and in cross section, which were dependent on the concentration of polymethylmethacrylate. In the in vitro incubation test, fiber with moderate-sized pores demonstrated the highest adsorption capacity. In the in vivo hemoperfusion study, the ratio of the high-mobility-group box chromosomal protein 1 concentration at the outlet versus the inlet of the column was significantly lower with the new column than with the control column during 4-h extracorporeal hemoperfusion. The normalized plasma level of high-mobility-group box chromosomal protein 1 at 12 h after the completion of hemoperfusion was significantly lower with the new column than with the control column., Conclusion: The newly developed polymethylmethacrylate column adsorbs high-mobility-group box chromosomal protein 1 during hemoperfusion in swine ALF model.