Postoperative pancreatic fistula (POPF) is one of the most severe complications after pancreatic surgeries. POPF develops as a consequence of pancreatic juice leakage from a surgically exfoliated surface and/or anastomotic stump, which sometimes cause intraperitoneal abscesses and subsequent lethal hemorrhage. In recent years, various surgical and perioperative attempts have been examined to reduce the incidence of POPF. We reviewed several well-designed studies addressing POPF-related factors, such as reconstruction methods, anastomotic techniques, stent usage, prophylactic intra-abdominal drainage, and somatostatin analogs, after pancreaticoduodenectomy and distal pancreatectomy, and we assessed the current status of POPF. In addition, we also discussed the current status of POPF in minimally invasive surgeries, laparoscopic surgeries, and robotic surgeries.

Recent evidence suggests that IL-17A regulates neutrophil-dependent organ injury. Accordingly, the purpose of this study was to determine the role of IL-17A in neutrophil recruitment after ischemia–reperfusion (I/R) and in subsequent liver injury. Two mouse models including wild-type and IL-17A knockout mice were evaluated for I/R injury. The medial largest lobe of the liver was clamped for 90 min. In another set of experiments, recombinant mouse (rm)IL-17A homodimer or rmIL-17A/F heterodimer were administered to knockout mice before I/R, and liver injury was investigated. Isolated Kupffer cells were incubated with rmIL-17A or rmIL-17F, and production of TNF-α was measured. Studies evaluating the extent of liver injury as measured by serum transaminase levels demonstrated similar levels in the acute phase (6 h) in these two models. In contrast, in the subacute phase (20 h) after I/R, both serum transaminase levels and percent of hepatic necrosis were significantly reduced in the knockout mice compared with the wild-type mice. This reduction in liver injury seen in the knockout mice was associated with suppression of chemokine and adhesion molecule expression and reduction in infiltration of neutrophils into the liver. Administration of rmIL-17A homodimer, but not IL-17A/F heterodimer, increased liver injury in the subacute phase of I/R in KO mice. TNF-α production by isolated Kupffer cells increased significantly in the cells incubated with rmIL-17A compared with rmIL-17F. These results indicate that IL-17A is a key regulator in initiating neutrophil-induced inflammatory responses and hepatic injury in the subacute phase after reperfusion.

These results indicated that HCV-related proteins may cause prolonged activation of KCs in the HCV-infected liver, leading to accumulation of inflammatory cytokines that contribute to DNA damage and carcinogenesis. Furthermore, function of KCs was difference between patients infected with and without HCV infection.

Background/Aim: Although perioperative management and operative techniques for pancreatic surgery have improved, postoperative pancreatic fistula (POPF) remains the major cause of morbidity and mortality following distal pancreatectomy (DP). The purpose of this study was to evaluate the superiority of the reinforced stapler compared to the bare triple row stapler. Patients and Methods: A total of 93 patients who underwent DP at the First Department of Surgery at Yamanashi University were examined. The patients were divided into two groups according to the closure method for the pancreatic stump; the bare triple-row stapler (BTRS) group and the reinforced triple-row stapler (RTRS) group. The postoperative outcomes were then compared in terms of several clinicopathological factors between the two groups. Results: Seven patients were diagnosed with Grade B/C POPF in this series. The incidence of POPF in the RTRS group was lower than that in the BTRS group (3.6% vs. 13.5%), although there was no significant difference (p=0.077). Further detailed analysis demonstrated that RTRS significantly reduced POPF compared to BTRS in obese patients with a BMI >25.0 kg/m 2 (p=0.038). Conclusion: Reinforced triple-row staplers may reduce the incidence of severe POPF, especially in obese patients with a BMI >25 kg/m 2 . Patients and MethodsPatients. A total of 93 patients who underwent DP at the First Department of Surgery at Yamanashi University between April 2013 and March 2018 were examined. This study was reviewed and approved by the ethics committee of the University of Yamanashi. To reduce the incidence of POPF following DP, we introduced the reinforced triple-row stapler for management of the pancreatic stump. The patients were divided into two groups, the bare triple-1013

In this study, we aimed to analyse human cancer cell–platelet interactions in functional cell analyses and explore the molecular mechanisms behind tumour progression. Various functional analyses of gastric cancer (GC) cells were performed after direct/indirect co-incubation with platelets derived from GC patients. Further detailed expression and signalling analyses were performed after co-culture with direct and indirect GC cells–platelet contact. Malignant behaviours of cancer cells, such as proliferation, migration, invasion and adhesion, were significantly enhanced after direct co-incubation with platelets. Microarray analyses demonstrated changes in multiple genes, including epithelial–mesenchymal transition (EMT)-related genes. Among them, matrix metalloproteinase 9 was notably upregulated, which was validated by quantitative reverse transcription–polymerase chain reaction and western blot. Further, this change was only observed after direct co-incubation with platelets. This study demonstrated that platelets from GC patients promote malignant behaviours of GC cells through EMT-related signalling, especially by direct contact with tumour cells.

Background and purposeApproximately 20% of all patients with colorectal cancer (CRC) are diagnosed at more advanced stages with synchronous distant metastasis, and the prognosis in these patients is usually poor. The aim of this study was to determine the factors that can identify subgroup(s) of patients with stage IV CRC who could benefit from curative (R0) resection of both primary and metastatic lesions.Patients and methodsA total of 126 patients with stage IV CRC who underwent surgical resection of primary tumor were retrospectively analyzed. Among these patients, 26 cases of R0 resection were further examined subsequently. Information on various clinicopathological factors of the patients were obtained from hospital records. Overall survival was estimated using the Kaplan-Meier method, and log-rank tests were used to compare survival distribution. All the factors with P < 0.05 in univariate analysis were analyzed in the Cox proportional hazards model.ResultsCEA negativity, left-sided tumor, R0 resection, differentiated histology, and nodal staging less than N1 were independent factors that predicted better prognosis in all the 126 patients with stage IV CRC. Tumor depth of T3 or less was significantly correlated with better survival in patients who had undergone R0 resection.ConclusionOur findings demonstrate that it is possible to select patients in whom surgical resection would yield better prognosis, from a variety of patient subgroups with stage IV CRC.

AIMTo investigate the clinical utility of alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC)-specific microRNA (miRNA) for monitoring and prognostic prediction of patients.METHODSWe performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC. We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility. We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples. Moreover, we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels, and also investigated the correlation of the selected miRNA expression levels and malignant potential.RESULTSAmong the five miRNAs selected from the miRNA array results, the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients (P < 0.05). In tissue samples, miR-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa. Conversely, in the AFPGC tissue, miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the non-AFPGC tissue samples (P < 0.05). Plasma miR-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the non-AFPGC patients (P < 0.05) and were strongly correlated with plasma AFP levels (r = 0.7975, P < 0.0001). Moreover, the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients. In contrast, no correlation was found between miR-122-5p expression levels and liver metastasis in the non-AFPGC patients.CONCLUSIONmiR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.

Background/Aim: Treatment algorithms for primary and recurrent hepatocellular carcinoma (HCC) are described in the current Japanese Clinical Practice Guidelines; however, primary and recurrent tumors exhibit several differences in oncological characteristics such as clinicopathological features and prognostic factors. This study aimed to investigate the prognostic factors for recurrent HCC including time of recurrence after primary hepatectomy, to elucidate appropriate treatment strategies in these patients. Patients and Methods: One hundred and nine patients who had undergone radical resection of primary HCC at our Hospital and had experienced intrahepatic recurrence were included in this study. Patients were categorized into the early-recurrence (ER, <1 year postoperatively) or the late-recurrence (LR, ≥1 year postoperatively) groups. Clinicopathological features were compared between the two groups for prognostic analyses. Results: Comparison of clinicopathological features between the ER and LR groups revealed that, at the time of recurrence, the ER group had a significantly higher frequency of multiple recurrences compared to the LR group. In univariate prognostic analysis, the time of recurrence (ER or LR) and the number of recurrent tumors (≥3) were significant prognostic factors after recurrence. Multivariate analysis revealed that three or more recurrent tumors and ER were independent prognostic factors for poor survival after recurrence. Conclusion: HCC is likely to recur, and the characteristics of recurrent HCC are distinct from those of primary HCC. To improve post-recurrence poor prognosis, new and more feasible algorithms, such as aggressive surgical treatment for cases with less than three recurrent tumors, which were revealed in the current study, are needed.Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide (1), and hepatitis B virus and hepatitis C virus are the two most common causes of lethal disease (2). Except for patients with chronic viral hepatitis, almost all patients with HCC are considered to have a history of chronic inflammation such as alcoholic hepatitis (3) and nonalcoholic fatty liver disease (4). In the current Japanese Clinical Practice Guidelines (5), treatment algorithms are proposed to determine the most suitable treatment strategy according to tumor-associated factors, such as tumor size, number of tumors, and vascular invasion, as well as patient factors, such as hepatic functional reserve, comorbidities, and general condition of the patient (6, 7). Among the several therapeutic approaches, surgical resection is considered the most appropriate treatment for clinically resectable tumors.However, new lesions frequently develop even after primary curative surgery (8), sometimes as metachronous HCC, that are difficult to differentiate from recurrence of primary tumor (9). Because treatment for metachronous HCC is identical to that for intrahepatic metastatic recurrence of primary tumors, both are considered together as recurrent HCC in clinical practice ...