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Purpose: The aim of this study is to identify gene expression signatures that accompany dedifferentiation at the cancer invasion front in colorectal cancer.Experimental Design: Two types of colorectal cancer were selected. Both types were well-differentiated adenocarcinomas at the superficial lesion. One type showed a dedifferentiated phenotype at the invasion front (type A, 13 samples); the other showed almost no dedifferentiated cancer cells at the invasion front (type B, 12 samples). Laser microdissection was combined with a cDNA microarray analysis to investigate the superficial lesions and the invasion front in colorectal cancers.Results: Eighty-three genes were differentially expressed between types A and B in the superficial lesions, and the samples of superficial lesions were divided correctly into two clusters by these genes. Interestingly, the samples of the invasion front were also divided into the two same clusters by these genes. The text mining method selected 10 genes involved in potential mechanisms causing dedifferentiation of cancer cells at the invasion front. The potential mechanisms include the networks of transforming growth factor-β, Wnt, and Hedgehog signals. The expression levels of 10 genes were calculated by quantitative reverse transcription-PCR and 8 genes were confirmed to be significantly differentially expressed between two types (P < 0.05). The gene expression profiles of 8 genes divided 12 test cases into two clusters with one misclassification.Conclusions: The molecular mechanisms constructed with 8 genes from three networks of transforming growth factor-β, Wnt, and Hedgehog signals were found to correlate with dedifferentiation at the invasion front of colorectal cancer.

Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years‐of‐age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes., Pedigree of a family with young‐onset diabetes due to a compound heterozygous inactivating ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). These mutations had been reported to be responsible for hypoglycemia in infancy and be functional inactivating mutations.

Risks for postoperative small bowel obstruction have been demonstrated in several reports, most of which indicated male sex was a risk factor, but with the reason remaining unknown. We tested the hypothesis that it could be because males have more visceral fat than females. This prospective observational study aims to examine risks of early postoperative small bowel obstruction (EPSBO) after colorectal cancer surgery and the association between visceral to subcutaneous fat area ratio (V/S ratio) and EPSBO.Four hundred and seventy-four patients who underwent colectomy for colorectal cancer in our hospital were enrolled in this study. The influence of several factors including V/S ratio on the development of EPSBO was analyzed.Thirty-one of the 474 patients (6.5%) developed EPSBO. EPSBO occurred more frequently in males (p = 0.03) and cases who developed postoperative anastomotic leakage (p 0.001) or wound infection (p = 0.02). Higher V/S ratio was strongly related to male sex (p 0.001). Multivariate analysis revealed higher V/S ratio (OR 2.25; p = 0.049) and anastomotic leakage (OR 5.86; p 0.001) were independent risk factors for EPSBO.Higher V/S ratio was significantly related to EPSBO, suggesting that one of the reasons EPSBO was more likely to occur in males because they have more visceral fat than females. Preoperative identification of this risk factor could help us watch out for this potential complication.

Background Early postoperative small bowel obstruction (EPSBO) is one of the most common complications after colorectal cancer (CRC) surgery, and clarification of its causes is desired. Several reports have demonstrated the risks of EPSBO, but few have focused on laparoscopic surgery for CRC and intraoperative maneuvers. We therefore prospectively examined the risk factors for EPSBO after laparoscopic CRC resection. Methods We prospectively enrolled 706 patients with CRC that underwent laparoscopic CRC resection in our hospital and affiliated hospitals. We analyzed several factors concerning EPSBO including intraoperative procedures. Results EPSBO developed in 43 of the 706 cases (6.1%). Univariate analysis showed that risk factors for EPSBO were male sex, increased operative time, repositioning of the small intestine before wound closure and anastomotic leakage. Risk factors for EPSBO according to multivariate analysis were increased operative time (odds ratio (OR) 2.41; P = 0.032), repositioning of the small intestine before wound closure (OR 3.58; P = 0.005) and anastomotic leakage (OR 3.91; P = 0.006). Conclusion To reduce EPSBO after laparoscopic CRC surgery, the operation should be finished as soon as possible without performing optional maneuvers. To avoid development to EPSBO, particular care is required in cases where the risk of anastomotic leakage is predicted to be high.

Background Defaecatory function is often poor after anterior resection. Denervation of the neorectum following high ligation of the inferior mesenteric artery (IMA) is a possible cause of impaired defaecatory function. The purpose of this randomized clinical trial was to clarify whether the level of ligation of the IMA in patients with rectal cancer affects defaecatory function. Methods Between 2008 and 2011, patients who underwent anterior resection for rectal cancer were randomized to receive either high or low ligation of the IMA. The primary endpoint was to demonstrate the superiority of low ligation in terms of defaecatory function. Results One hundred patients were enrolled in the study; 51 were randomized to high ligation of the IMA and 49 to low ligation. There were no differences between the groups in terms of clinical data, except tumour stage, which was more advanced in the high-ligation group (P = 0·046). Nor were there any differences in defaecatory function, self-assessment of defaecation, Faecal Incontinence Quality of Life scale or continence score between groups at 3 months and 1 year. The number of harvested lymph nodes was similar. The rate of symptomatic anastomotic leakage was 16 per cent in the high-ligation group and 10 per cent in the low-ligation group (P = 0·415). Conclusion The level of ligation of the IMA in patients with rectal cancer did not affect defaecatory function or the incidence of postoperative complications. Registration number: NCT00701012 (http://www.clinicaltrials.gov).