Endometrial cancer arises from the uterine body and fundus in many cases, but can also originate from the lower region of the uterine body through the upper region of the cervix. Such tumors are referred to as carcinoma of the lower uterine segment （LUS） or isthmus, and account for 3–3.5% of all cases of endometrial cancer. This relatively low incidence has permitted performance of only small-scale studies, but recently it has been reported that carcinoma of the LUS is associated with Lynch syndrome. The frequency of Lynch syndrome in cases of general endometrial cancer is 1–2%. In contrast, the frequency in patients with carcinoma of the LUS is much higher, with up to 29% of cases diagnosable with Lynch syndrome and a high frequency of MSH2 mutation found in one study. This suggests that further investigation of the clinical and pathological characteristics of carcinoma of the LUS and the association with Lynch syndrome is required through performance of a large-scale survey.

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Polyposis staging system is a need to develop a consensus regarding categories of increasing polyposis severity because in advance to the ultimate surgical intervention （total colectomy） we already have or will have a choice of variety of interventions such as endoscopic and chemopreventive interventions. A given category of adenomatosis severity should carry with it a corresponding intervention, so as the aggressiveness of intervention increasing as stage increases. The “clinically significant” should only be considered as an improvement in stage or delay in worsening of stage. This is a preliminary polyposis staging system under preparing by the International Society of Hereditary Gastrointestinal Tumors （InSiGHT）. It is hoped that this would enable a gradual move toward adoption of standardized, evidence-based approaches to polyposis staging and treatment.

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[Aims] Duodenal adenocarcinoma is the leading cause of death in FAP patients besides colorectal cancers. The aims of this study were to describe the natural history of duodenal lesions with FAP patients in our hospital. [Patients and Methods] This study involved 80 patients with FAP being diagnosed by colonoscopy and upper gastrointestinal endoscopy between 1997 and 2012 at the National Cancer Center Hospital, Tokyo, Japan. We reported the clinicopathological features and management and the Spigelman classification of the duodenal lesions. [Results] Forty-one (51%) of the 80 FAP patients had duodenal adenomas (extra-ampullary) and five (6%) had duodenal adenocarcinoma. Among 36 patients with duodenal adenomas who were followed up, 4 (11%) patients were treated with endoscopic resection. Three (8%) of 36 lesions developed duodenal adenocarcinoma. In this study, there were no patients who died of duodenal adenocarcinoma. Duodenal adenocarcinoma was detected in four (50%) of eight patients with stage IV on Spigelman classification during the study. [Conclusions] The death from duodenum lesions was not observed during the study. We consider the careful follow-up examination using endoscopy and endoscopic resection is useful to prevent the tumor progression of duodenal lesions. In addition, the Spigelman classification might be beneficial for the risk assessment of duodenal malignant potential.

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Purpose: Our aim was to evaluate the prevalence andnature of ileal pouch and non-pouch adenomas andcarcinoma in patients with familial adenomatouspolyposis （FAP）. Patients and methods: This was aretrospective study of 40 FAP patients with Kock’scontinent ileostomy（Kock）（n=8）, ileorectal anastomosis（IRA）（n=8）, and ileal pouch-anal anastomosis（IPAA）（n=24）. All patients were followed by endoscopy in theileal pouch and non-pouch mucosa. Results: Twenty of 32pouch patients（Kock and IPAA） developed adenomas in the ileal pouch mucosa, and all patients with 8 IRApatients developed adenomas in the rectal mucosa. Theprevalence of ileal adenomas was significantly higher inpouch patients than in IRA patients（P ＜ 0.01）. Threecases of adenocarcinomas were found in the ileal pouchmucosa. The risk of adenoma development in the ilealpouch was 10%, 45%, and 90% at 5, 10, and 20 years offollow-up, respectively after proctocolectomy with Kockand IPAA. The risk of rectal adenoma after colectomywith IRA was 50%, 75%, and 100% at 5, 10, and 20 yearsof follow-up, respectively. Conclusion: Our results showa high frequency of adenomas in the ileal pouch mucosa,with evolution into carcinoma in some patients. Regularendoscopic surveillance of the pouch is recommended.

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We reported our experience of endoscopic treatment for colorectal polyps in familial adenomatous polyposis (FAP) patients (3 men and 5 women, mean age: 29.9 years) between October 2007 and June 2012 in Hiroshima University Hospital. Most of colorectal polyps were resected by polypectomy. The total number of endoscopic treatment in all FAP patients was 32 times, and the average number of examination per patient was 4.0 times (range: 1-18). The total number of removed colorectal polyps was 1,056 lesions (1,054 adenomas and 2 carcinoma in adenoma), and the average number of removed polyps per patient was 132.0 lesions (range: 40-636). Two severe complications (One is delayed perforation and another is bleeding after polypectomy) occurred. Although the case with the bleeding after polypectomy was controlled by endoscopic hemostasis, the case with the delayed perforation needed surgical operation. No colorectal carcinomas occurred over the average observation period of 23.6 months (range: 2-60 months)

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The present double-blind, randomized, placebocontrolled clinical study was performed to evaluate the influence of low-dose aspirin enteric-coated tablets （100 mg/day for 6–10 months） in a total of thirty-four patients with familial adenomatous polyposis （17 each in the aspirin and placebo groups）. The sizes of colonic polyps tended to be higher in the placebo as compared to the aspirin group with an response ratio of 2.33（95% confidence interval 0.72–7.55） and subgroup analysis revealed patients with a mean baseline polyp size of ＜ 2 mm to show significant reduction of mean polyp sizes （diameter and height） in the aspirin group. Stratified analysis further revealed tendencies for greater polyp size reduction by aspirin in the subgroups who were women, aged ＜ 41 years, non-smokers, non-drinkers, with an APC gene mutation, positive for beta-catenin and for intraepithelial COX-2 staining. Adverse events occurred in 3 patients, all in the aspirin group, and in one case this required discontinuation of the drug. The results thus indicated a potential for aspirin to reduce colonic adenoma development in patients with familial adenomatous polyposis, but careful follow-up is needed to avoid or rapidly counter adverse events.

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Tylosis with esophageal cancer（TOC）/Howel-Evans syndrome is an autosomal-dominant syndrome characterized by palmoplantar keratoderma, oral precursor lesion, and high-risk group of esophageal cancer. Previous studies localized the TOC locus to a small genomic region of 17q25.1–q25.2. Using a targeted capture array and next-generation sequencing, two kinds of missense mutations of RHBDF2 gene were detected in genomic DNA from patients with TOC. RHBDF2 is a family of seven transmembrane–spanning protein called rhomboids, but has been not yet known its function. It is thought that RHBDF2 regulate protease activity and EGF signaling by targeting ligands of EGFR. The study of Baydon DC et al suggested that the altered RHBDF2 protein, which was derived from the mutant alleles, had a property of gain-of-function, because of sustaining of EGFR signaling. It is assumed that this sustained EGFR signaling leads to hyperproliferative state. Moreover, Baydon DC et al proposed a hypothesis that tylosis results from dysregulated wound repair that lead to precancerous lesions in the esophagus and nonkeratinized epithelium of the upper gastrointestinal tract. Because similar biochemical characteristics were observed in not only TOC but also sporadic esophageal cancer, it is concerned some esophageal cancers might be resistant to treatment with EGFR-inhibitors. Therefore, developing therapies targeted to RHBDF2-regulated pathways could be more effective against esophageal cancers.

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