Shunichiro Komatsu

The G2 checkpoint inhibitor CBP-93872 increases the sensitivity of colorectal and pancreatic cancer cells to chemotherapy

CBP-93872 suppresses maintenance of DNA double-stranded break-induced G2 checkpoint, by inhibiting the pathway between ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) activation. To examine the potential use of CBP-93872 for clinical applications, we analyzed the synergistic effects of platinum-containing drugs, oxaliplatin and cisplatin, pyrimidine antimetabolites, gemcitabine and 5-fluorouracil (5-FU), in combination with CBP-93872, on cell lethality in colorectal and pancreatic cancer cell lines. Treatment with CBP-93872 significantly increased cancer cell sensitivities to various chemotherapeutic agents tested through suppression of checkpoint activation. Our results thus reveal that combination treatment of CBP-93872 with known chemotherapeutic agents inhibits phosphorylation of ATR and Chk1, and induces cell death.

Gut microbiota and bacterial translocation in digestive surgery: the impact of probiotics

PurposeIt is conceivable that manipulation of the gut microbiota could reduce the incidence or magnitude of surgical complications in digestive surgery. However, the evidence remains inconclusive, although much effort has been devoted to randomized controlled trials (RCTs) and meta-analyses on probiotics. Furthermore, the mechanism behind the protective effects of probiotics appears elusive, our understanding of probiotic actions being fragmentary. The objective of this review is to assess the clinical relevance of the perioperative use of probiotics in major digestive surgery, based on a comprehensive view of the gut microbiota, bacterial translocation (BT), and host defense system.MethodsThe first part of this article describes the pathophysiological events associated with the gut microbiota. Results of RCTs for the perioperative use of probiotics in major digestive surgery are reviewed in the latter part.ResultsThe development of the structural and functional barrier to protect against BT primarily results from the generally cooperative interactions between the host and resident microbiota. There is a large body of evidence indicating that probiotics, by enhancing beneficial interactions, reinforce the host defense system to limit BT. The perioperative use of probiotics in patients undergoing hepatobiliary and pancreatic surgery is a promising approach for the prevention of postoperative infectious complications, while the effectiveness in colorectal surgery remains controversial due to substantial heterogeneity among the RCTs with small sample populations.ConclusionsFurther studies, such as multi-center RCTs with a larger sample size, are necessary to confirm the clinical relevance of probiotic agents in major digestive surgery.

Surgical outcome of laparoscopic hepatic resection for hepatocellular carcinoma: A matched case–control study with propensity score matching

Background: Although the number of reports on laparoscopic hepatic resection (LHR) has increased, studies of long-term outcomes regarding tumor recurrence and patient survival compared to the conventional open approach are limited. We evaluated the long-term survival and feasibility of LHR in patients with hepatocellular carcinoma (HCC). Patients and Methods: A retrospective analysis was performed on the clinical data of patients who underwent hepatic resection for primary HCC between August 2000 and December 2013. The patients were divided into the LHR or open hepatic resection (OHR) groups. To control for selection bias in the two groups, propensity score matching was used at a 1:1 ratio based on the following covariates: Child–Pugh grade, tumour size, tumour number and tumour location. Following propensity score matching, thirty patients were included in the LHR group and thirty were included in the OHR group. Results: The respective disease-free survival rates at 1 year, 3 years and 5 years were 78.4%, 61.1% and 38.9%, respectively, for the LHR group, and 89.3%, 57.5% and 47.9%, respectively, for the OHR group (P = 0.89). Also, the overall survival rates at 1 year, 3 years and 5 years were 96.4%, 68.2% and 62.5%, respectively, for the LHR group and 100.0%, 95.8% and 72.3%, respectively, for the OHR group (P = 0.44). Conclusions: According to our study, using propensity score matching, LHR for HCC is safe, feasible and comparative, with good oncologic results.

Anatomy of the right colic vein and pancreaticoduodenal branches: a surgical landmark for laparoscopic complete mesocolic excision of the right colon

PurposeKnowledge of mesenteric venous anatomy is important to safely perform laparoscopic complete mesocolic excision (CME) of the right colon. Despite their previously reported diversity, consistent features of the right colonic and pancreatic veins can be discerned. The objective of this study was to evaluate anatomical consistency of the right colic vein (RCV) and the pancreaticoduodenal vein associated with the colic vein (PDV-C).MethodsThis study included 125 consecutive patients undergoing contrast-enhanced multidetector-row CT of the abdomen. Images of 100 of these cases were retrospectively reviewed for the positioning of the colonic, gastric and pancreatic veins associated with the superior mesenteric vein (SMV). RCV were classified as three types: Type-I, running on the ventral aspect of the pancreatic head and draining into the right lateral wall of the SMV; Type-II, running apart from the pancreatic head and directly draining into the SMV; and Type-III, draining into the tributaries of the SMV.ResultsThe RCV was identified in 88% of cases, in which the frequencies of Type-I, -II and -III anatomies were 84.1, 9.1, and 6.8%, respectively. All of the Type-I RCVs formed a common trunk with other veins, including the gastroepiploic vein (93.2%) and the superior RCV (59.5%). The PDV-C joined the RCV in 63.5% of the Type-I cases.ConclusionsAnatomical consistency of the RCV together with the PDV-C is present in the majority of cases. Our findings support the view that the appearance of the veins is a useful landmark for laparoscopic CME of the right colon.

Effects of synbiotics on ileal microbiota

Background & objectives: Despite advancements in molecular-based methods, the composition of the human ileal microbiota and the effects of synbiotics/probiotics on its microbes remain poorly understood. The aim of this study was to determine the composition of the mucus microbiota in the human ileum and to assess the effects of oral administration of synbiotics on the microbiota. Methods: As part of a clinical trial for synbiotics treatment and surgical infection, ileal mucus was sampled when resection of the ileocecal portion was required. The microbiota composition was examined using 16S rRNA-targeted real-time-quantitative polymerase chain reaction. Results: A total of 33 samples from the synbiotics group and 39 from the control group were analyzed. Total numbers of bacteria in the ileum were 108.5 cells/g in the synbiotics group and 108.4 cells/g in the control group, in which obligate anaerobes were dominant over facultative anaerobes. The level of Enterobacteriaceae was significantly lower in the synbiotics group than in the control group. The administered probiotics species Lactobacillus casei strain Shirota and Bifidobacterium breve strain Yakult were detected in 42 and 76 per cent of the synbiotics group, respectively. No significant correlations were observed between tumour stage/size and the various microbes present, except for a negative correlation between tumour size and Bifidobacterium. Interpretation & conclusions: The present analysis of a substantial number of samples from surgically resected intestines showed an abundance of obligate anaerobes as a characteristic feature of the ileal mucus microbiota. Our results also indicated that the synbiotics intervention induced a prominent reduction in Enterobacteriaceae in the ileal microbiota.

Feasibility of umbilical loop ileostomy in overweight and obese patients with rectal cancer during laparoscopic surgery: Preliminary results

We examined the feasibility of umbilical diverting ileostomy for overweight and obese patients with rectal cancer undergoing laparoscopic surgery. Four patients who were overweight or obese (BMI > 27 kg/m2) were initially scheduled for the creation of a conventional loop ileostomy. Intraoperatively, however, this was considered too complicated because of thick subcutaneous fat, bulky mesentery, or both. Instead, patients received a diverting ileostomy with the placement of an umbilical stoma. All patients had protruding umbilical ileostomies. No severe stoma‐related complications were encountered. One patient had minor skin dehiscence, and another had paralytic ileus but resumed oral intake after a short time. Performing a temporary loop ileostomy at the umbilicus was safe and feasible in this small group of overweight and obese patients. This stoma placement may avoid the problems inherent to conventional loop ileostomy in obese subjects.