Search

Abstract Background We recently reported the relapse-free survival (RFS) significance of the combination of CD4+ and forkhead box P3+ (FOXP3) T-cell densities identified by immunohistochemistry in patients with stage I, II, and III colorectal cancer (CRC) who underwent curative resections. This study was designed to determine the optimal combination of markers that predict recurrence in patients with T factors of T3/T4a stage II CRC by applying a novel Bayes decision rule. Methods Using 137 cancer tissue specimens from T3/T4a stage II patients, 12 clinicopathologic and immune factors were analysed as predictive candidates for recurrence. Results Our study showed that the combination of low CD4+ and low FOXP3+ T-cell densities resulted in extremely poor RFS. Conclusions Adjuvant chemotherapy may be considered for patients with a combination of low CD4+ and low FOXP3+ T-cell densities. The discovery of this new prognostic indicator is important for the appropriate management of patients undergoing curative resection for T3/T4a stage II CRC.

Abstract Background Cancer stem cells (CSCs) are thought to play important roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. We have successfully induced cancer stem-like sphere cells (CSLCs) which possess enhanced chemoresistance and metastatic potential. To enable the development of targeted therapy against CSLCs, we identified a gene responsible for this phenotype in CSLC. Methods Human hepatoma cell line SK-HEP-1 was used for CSLC induction with a unique sphere inducing medium, and HuH-7 cells were used as non-sphere forming cells in the same condition. RNA-sequencing was performed followed by validation with quantitative RT-PCR and western blotting. Knockdown experiments were done by using CRISPR-Cas9 genome-editing, and the rescue experiments were performed using the expressing plasmid vector. Chemoresistance and liver metastasis of the cells, was studied following the splenic injection of cells to severely immune deficient mice and evaluated using the MTS assay. Quantification of exosomes in the medium was done using ELISA. Results RAB3B was identified as an up-regulated gene in both CSLCs and prognostically poor hepatocellular carcinoma (HCC) by RNA-sequencing. RAB3B-KD cells showed altered CSLC phenotypes such as sphere formation, chemoresistance, and metastatic potentials, and those were rescued by RAB3B complementation. Increased exosome secretion was observed in CSLCs, and it was not observed in the RAB3B-KD cells. In addition, the RAB3B expression correlated with the expression of ABCG2, APOE, LEPR, LXN, and TSPAN13. Conclusion The up regulation of RAB3B may play an important role in the chemoresistance and metastatic potential of CSLCs.

Abstract Aim The impact of sustained virologic response (SVR) on surgical outcomes for patients with hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the influence of SVR on long‐term surgical outcomes after hepatectomy. Methods This multicenter study included 504 patients who underwent curative resection for HCV‐related HCC. Patients with a history of HCC treatment, HBV infection, poor liver function, and tumor with major vascular invasion were excluded. Long‐term surgical outcomes (overall survival [OS] and recurrence‐free survival [RFS]) among patients who achieved SVR before hepatectomy (Pre‐SVR group: 58 patients), after hepatectomy (Post‐SVR group: 54 patients), and without SVR (Non‐SVR group: 186 patients) were compared after adjusting for 13 confounding factors. Using the surgically resected specimens, comparison of the pathological changes in liver fibrosis between the first and second hepatectomy were analyzed. Results Patients with SVR were younger, had better liver function, and less liver fibrosis compared to patients without SVR. Propensity score‐matched OS and RFS were significantly better in Pre‐SVR group than Non‐SVR group (P = .029 and P = .009, respectively). Inverse probability‐weighted OS and RFS were also significantly better in the Post‐SVR group (P = .001 and P = .021, respectively) than in the Non‐SVR group. Histopathological evaluation revealed that only the patients with SVR had regression of liver fibrosis (P

Abstract Biliary tract cancer, which includes intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, and ampullary cancer, is an intractable disease with a dismal prognosis. Prognosis is particularly poor in cases involving vessels or lymph nodes. Hepatobiliary pancreatic surgeons worldwide have consistently focused on improving surgical treatment, perioperative management, and chemotherapy to improve the outcomes of these diseases. There has been significant progress even in the last 2 years (2017 and 2018), such as promising findings reported by studies on the optimal extent of surgical treatment and multi‐institutional randomized controlled trials on adjuvant chemotherapy. We overview the current trends and advancements made in surgical treatment in 2017 and 2018.

Abstract Background and aims Imaging diagnosis of gallbladder cancer remains difficult to achieve preoperatively. We developed a novel approach based on laparoscopic whole‐layer cholecystectomy (LWLC) and laparoscopic gallbladder bed dissection (LGBD) for total biopsy, for ultimately determining the optimal treatment strategy for suspected gallbladder cancer detected on preoperative imaging. Here, we describe a case series of patients who underwent this procedure at our institution. Methods We retrospectively examined clinicopathological data of consecutive patients with suspected gallbladder carcinoma at Yamaguchi University Graduate School of Medicine from September 2016 to July 2018 on which a laparoscopic approach was used. Preoperative imaging findings suggestive of gallbladder cancer were defined as follows: elevated lesion >10 mm in diameter, increasing tumor size over time compared with the previous imaging, sessile lesion, irregular wall thickness lesion mimicking cancer, elevated lesion with dense enhancement, or positive results on fluorodeoxyglucose positron emission tomography. LWLC was performed for early‐stage or suspected malignant lesions without liver invasion, and LGBD was performed for lesions with an unclear border between the gallbladder and the liver. When postoperative pathological examination revealed the presence of gallbladder cancer invading into the subserosal layer, additional gallbladder bed resection and regional lymphadenectomy were considered. Patient characteristics, perioperative findings, pathological findings, and postoperative outcomes of patients who underwent LWLC or LGBD were reviewed retrospectively, and the short‐term outcomes of the laparoscopic approach were analyzed. Results Fifteen consecutive patients were included in the study. The median age of the patients was 63 years (IQR 42‐76 years); 7 patients were males. We performed LWLC in 12 cases and LBGD in 3 cases. Median (IQR) operation time was 159 (140‐193) min and median blood loss was 10 (5–30) mL. No bile leakage caused by intraoperative perforation of the gallbladder was seen. Median hospital stay was 7 (5–9) days. Only one patient developed postoperative complications (abdominal abscess). Histologically, gallbladder cancer was diagnosed in five cases (pT1a, n = 2; pT2, n = 3), and two of the pT2 patients underwent additional open surgery. Conclusions Our laparoscopic‐based approach for suspected gallbladder cancer might represent a safe strategy and could play an important role in defining the optimal treatment strategy.

The optimal treatment for hepatocellular carcinoma (HCC) should be selected based on tumor conditions, liver functional reserve, and performance status. Surgical treatment, such as liver resection and liver transplantation, is the most favorable treatment method; however, its indication criteria differ according to each country’s guidelines. In Western countries, liver resection is indicated only for early-stage HCC patients with Barcelona-Clinic Liver Cancer staging classification (BCLC) 0/A. While in Asian countries, liver resection is one of the treatment options for advanced HCC, such as BCLC B/C. Recently, the treatment of HCC is about to enter a drastic transitional period. It started with the widespread use of minimally invasive surgery for HCC, followed by a high rate of hepatitis C virus eradication with the advent of direct acting antivirals and developing a multidisciplinary treatment for highly advanced HCC. As a result, the importance of liver resection for HCC is increasing, and it is time to reconsider the criteria for selecting treatment methods for HCC patients. This article outlines current topics in the surgical treatment of HCC.

Objective: Enteral administration of synbiotics has been reported to be beneficial during various types of surgery, but its clinical value in elderly surgical patients remains unclear. The aim of this study was to quantitatively evaluate the changes in gut microbiota and environment induced by perioperative synbiotic therapy, and to investigate whether it is possible to reduce infectious complications in elderly patients undergoing gastroenterological surgery. Methods: Forty-eight patients over the age of 70 y were randomized into a group receiving 7 d of preoperative and 10 d of postoperative synbiotic therapy (S group) and a control group without synbiotic therapy (C group). A fecal sample collected before and after surgery in each group was used for a quantitative evaluation of the microbiota. Results: Forty-eight patients completed the trial (25 in the S group and 23 in the C group). Synbiotic therapy significantly maintained the status of Bifidobacterium and Lactobacillus, whereas the number of Enterobacteriaceae, Staphylococcus, and Pseudomonas was significantly decreased. The total organic acid and short-chain fatty acid concentrations were increased, and the pH was markedly decreased, in the S group compared with the C group. The incidence of postoperative infectious complications was 12% in the S group and 36% in the C group, however, the difference did not reach statistical significance (P = 0.06). A multivariate analysis revealed that only the use of perioperative blood transfusion was an independent risk factor for infectious complications. Conclusions: Synbiotic therapy improved the intestinal microbial environment, and might decrease the incidence of infectious complications in elderly surgical patients. [ABSTRACT FROM AUTHOR]