A novel Lynch syndrome pedigree bearing germ-line MSH2 missense mutation c.1808A>T (Asp603Val).

We report the first pedigree of Lynch syndrome bearing a germ-line MSH2 missense mutation c.1808A>T (Asp603Val). Until now, this missense mutation, in exon 12 of MSH2, was identified as a variant of unknown significance in the International Society for Gastrointestinal Hereditary Tumours database. In vitro induction mutagenesis experiments indicated that the MSH2 mutant protein (Asp603Val) is easily degraded in embryonic stem cells, albeit there is no clinical information concerning this mutant. Our pedigree includes four patients with Lynch syndrome-associated malignancies and clinically matches the Amsterdam II criteria. The proband, a female, first had an endometrial cancer at the age of 49 and then mantle cell lymphoma, colonic and gastric adenocarcinomas and neuroendocrine carcinoma, successively. Her mother also had Lynch syndrome-associated malignancies, including colonic, uterine and gastric cancers, and her elder son had rectal cancer. In the germline of the proband and her son, an MSH2 missense mutation c.1808A>T was discovered. Immunohistochemical analyses indicated that the expression of the MSH2 protein was decreased in the tumors, such as gastric cancer and neuroendocrine carcinoma, due to the missense mutation c.1808A>T. This study showed that the MSH2 missense mutation c.1808A>T (Asp603Val) is a likely pathogenic mutation and is responsible for typical Lynch syndrome-associated malignancies, including neuroendocrine carcinoma.

Risks for Rebleeding and In-Hospital Mortality after Gastrointestinal Bleeding in a Tertiary Referral Center in Japan.

BACKGROUND: Gastrointestinal bleeding (GIB) is one of the most common medical emergencies. We investigated the overall mortality after GIB in our institute and analyzed the prognostic factors in upper GIB (UGIB) and lower GIB (LGIB) separately. SUMMARY: Between January 2010 and December 2018, 190 patients diagnosed with GIB in our hospital were retrospectively enrolled. Clinical records and biological data were collected. Risks for rebleeding and in-hospital mortality were assessed by a logistic regression analysis. Overall, the rebleeding rate and in-hospital mortality were 22.6 and 7.6%, respectively. GIB itself was not the direct cause of death in any cases. While older age (>65 years) was a significant risk factor for rebleeding in UGIB with an OR of 6.1 and 95% CI of 1.3-29.1, a poorer performance status (PS; ≥3) was a strong risk factor for rebleeding in LGIB, with an OR of 11.8 and 95% CI of 1.7-83.8. Poor PS and tachycardia (>100/min) were significantly associated with mortality in both UGIB and LGIB. In contrast, hypoalbuminemia (<3.0 g/dL) was associated with the mortality in LGIB alone. Key Messages: There were considerable differences in the risk factors for rebleeding and in-hospital mortality between UGIB and LGIB. The overall in-hospital mortality was 7.9% after GIB, including that a substantial portion of patients with GIB died from systemic complications after successful endoscopic hemostasis. Physicians need to diligently perform systematic treatment for GIB, which may be particularly important in societies of advancing aging, like Japan.

Aggressive Inflammatory Myofibroblastic Tumor without Anaplastic Lymphoma Kinase Gene Rearrangement in the Rectum with Liver Metastasis.

Inflammatory myofibroblastic tumor is a rare intermediate-grade tumor. We herein report the case of an 81-year-old man with rectal ulceration and abnormal retroperitoneal soft tissue with a high serum level of IgG4. The administration of prednisolone reduced the retroperitoneal lesion; however, the rectal ulceration expanded. Surgical resection was performed. A histopathological examination revealed proliferating spindle cells accompanied by inflammatory cells and plasma cells. Liver metastasis emerged two months after surgical resection, and the histology of the proliferating spindle cells sampled by a fine-needle biopsy was similar to that of the rectal tissue. The patient ultimately died of inflammatory myofibroblastic tumor.

True Primary Enterolith Treated by Balloon-assisted Enteroscopy.

Primary enterolith is a rare condition that can induce ileus and intestinal perforation. We report the first case of a true primary enterolith treated by balloon-assisted enteroscopy. The patient presented with a small intestinal ileus. After its improvement following the insertion of an ileus tube, radiography with amidotrizoate sodium meglumine detected a round, movable defect in the ileum measuring 42 mm diameter. The patient was diagnosed with a primary enterolith based on her past history. The enterolith was fractured and removed using balloon-assisted enteroscopy. This case suggests that balloon-assisted enteroscopy may be an effective non-invasive treatment option for enteroliths.

Successful treatment with infliximab for refractory para-ileostomal ulceration in a patient with BehÒ«et's disease.

BehÒ«et's disease (BD) is a chronic disorder involving multiple organ systems including the small and large intestines. A 46-year-old female diagnosed with intestinal BD presented with ileocecal perforation and diffuse peritonitis and subsequently underwent ileocolic resection with ileostomy. After surgery, she suffered from refractory para-ileostomal ulceration associated with BD. Most importantly, however, treatment with infliximab was significantly effective in healing the ulceration. This is the first report of para-ileostomal ulceration associated with BD successfully treated with infliximab, suggesting the possible use of infliximab as a therapeutic option for para-stomal ulcers related to BD.