Natural history of upper and lower gastrointestinal bleeding in hemodialysis patients: A dual-center long-term cohort study.

BACKGROUND AND AIM: Knowledge on the risk of gastrointestinal (GI) bleeding in hemodialysis patients is limited. We evaluated the risk of GI bleeding in hemodialysis patients compared with non-hemodialysis patients. METHODS: We performed a retrospective cohort study from 1996 to 2017 at the Graduate School of Medicine, University of Tokyo, and Horinouchi Hospital. We analyzed patients on hemodialysis for chronic renal failure and controls not on hemodialysis. The primary endpoint was GI bleeding. A survival analysis was performed to estimate the cumulative incidence and hazard ratio of GI bleeding. RESULTS: A total of 14 451 patients were analyzed (417 hemodialysis and 14 034 non-hemodialysis patients). In total, 524 GI bleeding events occurred. Upper and lower GI bleeding occurred in 432 and 92 patients in the hemodialysis and non-hemodialysis groups, respectively. The most frequent source of upper and lower GI bleeding was gastric ulcer and colonic diverticular bleeding, respectively. The cumulative incidence of GI bleeding was 4.44% at 1 year, 7.15% at 3 years, and 10.40% at 5 years in hemodialysis patients; the respective rates were 2.35%, 2.98%, and 3.79% in non-hemodialysis patients during a mean follow-up period of 3.5 years. Hemodialysis was significantly associated with an increased risk of GI bleeding after adjustment (hazard ratio 1.67, P = 0.01, 95% confidence interval 1.13-2.50). CONCLUSIONS: Hemodialysis patients had a GI bleeding rate of 10% over 5 years, and hemodialysis was a risk factor for GI bleeding.

Is surveillance endoscopy necessary after colectomy in ulcerative colitis?

The role of surveillance endoscopic followup in colectomized patients with long standing total colitis is controversial. Here, we aimed to clarify its usefulness for the early detection of dysplasia and cancer in this group of patients. Ninety-seven colectomised UC patients followedup by surveillance endoscopy were retrospectively investigated by reviewing the pathological reports. Patients had received either subtotal colectomy and ileo-rectal anastomosis (IRA) or total proctocolectomy and ileal anal anastomosis (IPAA). Definite dysplasia was diagnosed in 4 patients, who had received IRA; among them, 2 were carcinoma with submucosal invasion, and one was a high-grade dysplasia. Postoperative surveillance endoscopy is useful for the detection of early cancer in the remaining colonic mucosa of UC patients, and those receiving IRA, in which rectal mucosa is left intact, would be good candidates. However, its effectiveness for patients receiving IPAA, in which the rectal mucosa is resected, needs further investigation.

[A case report of anorectal malignant melanoma showing a complete response after DTIC/ACNU/VCR therapy].

We report herein the case of a 64-year-old male who presented with hematochezia. The patient was diagnosed with malignant melanoma of the anorectum using colonoscopy. Preoperative studies revealed no distant metastases, and he underwent Miles operation. Pathological exams revealed that the tumor had invaded the submucosa with lymphatic and venous invasion. Cancer cells were found in regional lymph nodes. Post-operative CT scan demonstrated multiple metastases in the liver, and he received two courses of combined chemotherapy, DAV regimen (dacarbazine: DTIC 100 mg iv days 1-5, nimustine hydrochloride: ACNU 100 mg iv day 1, vincristine sulfate: VCR 1 mg iv day 1), leading to a complete response. However, malignant melanoma cells were found in hernia contents at the operation for left inguinal hernia, which led to a diagnosis of recurrent malignant melanoma. The patient has subsequently been well without any sign of recurrence including liver metastases. To our knowledge, this is the first report of a complete response in a patient with multiple liver metastases of anorectal malignant melanoma after DAV regimen.

Basic fibroblast growth factor enema improves experimental colitis in rats.

BACKGROUND/AIMS: Growth factors have a potential role in gastrointestinal mucosal repair. Although basic fibroblast growth factor (bFGF) is known to contribute to wound healing, however, the role of bFGF in the treatment of inflammatory bowel disease has not been established. The aim of this study is to investigate the therapeutic effects of intracolonic bFGF administration on both the clinical symptoms and histological mucosal repair in an experimental model of colitis in rats. METHODOLOGY: Acute colitis was induced with 5% dextran sulfate sodium (DSS) given for one week in drinking water. The rats were treated daily with recombinant human bFGF enema (400 microg/kg/day) or vehicle once daily from day 1 to day 7. Clinical score (stool consistency, weight loss and hemoccult/gross rectal bleeding), colon length and histological score of mucosal injury in colonic tissue samples were analyzed. RESULTS: Administration of bFGF enema significantly reduced clinical score (p < 0.01) and histological score (p < 0.01). No specific side effect of bFGF was noted. CONCLUSIONS: These results suggest that bFGF enema is clinically safe and useful in the treatment of inflammatory bowel disease. BFGF enema may contribute as a novel therapy of IBD.

Gene expression signature and the prediction of ulcerative colitis-associated colorectal cancer by DNA microarray.

PURPOSE: Ulcerative colitis (UC) is associated with a high risk of colorectal cancer. To identify genes that could predict the development of cancer in UC, we conducted a DNA microarray analysis using nonneoplastic rectal mucosa of UC patients. EXPERIMENTAL DESIGN: Gene expression in nonneoplastic mucosa of 53 UC patients were examined. Gene expression profiles were examined using human Genome U133 Plus 2.0 gene chip array (Affymetrix). Among 53 UC patients, 10 had UC-associated cancer (UC-Ca group) whereas 43 did not (UC-NonCa group). RESULTS: By comparing gene expression profiles of nonneoplastic rectal mucosae between the UC-Ca and UC-NonCa groups, we could identify 40 genes that were differentially expressed between two groups. The list of discriminating genes included low-density lipoprotein receptor-related protein (LRP5 and LRP6). Previous studies suggested that LRP5 and LRP6 expression promotes cancer cell proliferation and tumorigenesis and are considered as candidate oncogenes. In the present study, both LRP5 and LRP6 showed significantly higher expression in the UC-Ca group, which suggests the importance of these genes in the development of UC-associated colorectal cancers. With the 40 selected discriminating genes, we did class prediction of the development of colorectal neoplasms in UC patients. Using the k-nearest neighbor method and the support vector machine, we could predict the development of UC-associated neoplasms with an accuracy of 86.8% and 98.1%, respectively. CONCLUSIONS: These findings have important implications for the early detection of malignant lesions in UC and may provide directions for future research into the molecular mechanisms of UC-associated cancer.

Cytomegalovirus infection in ulcerative colitis.

OBJECTIVE: Cytomegalovirus (CMV) infection has been reported as an exacerbating factor in inflammatory bowel disease but the relationship between CMV infection and ulcerative colitis (UC) remains unclear. There has been no detailed research to elucidate the clinicopathologic features of CMV infection in UC using surgical specimens. The aim of this study was to investigate the clinicopathologic features of CMV infection in UC patients who had undergone colectomy. MATERIAL AND METHODS: Surgical specimens taken from UC patients were examined for CMV infection. The patients were divided into three groups: severe, refractory, and UC-associated dysplasia or cancer according to the operative indications. CMV infection rates were evaluated and a comparison of clinical parameters was made between CMV-positive and CMV-negative patients, and the risk factors for CMV infection were analyzed using multivariate analyses. RESULTS: It was found that 25% of 32 patients were positive for CMV in the severe UC group; 8.3% of 72 patients were positive for CMV in the refractory UC group. None of the 22 patients was positive for CMV in the UC-associated dysplasia or cancer group. The CMV-positive rate in the severe UC group was significantly higher than that in the other groups (p<0.05). Patients' age at the time of operation was higher in the CMV-positive group than in the CMV-negative group among the patients with severe UC (p<0.01), and age at operation was an independent risk factor for CMV infection. CONCLUSIONS: CMV is found more frequently in severe UC than refractory UC and UC-associated cancer or dysplasia. Higher age can be a risk factor for CMV infection in patients with severe UC. However, a high steroid dose may not always be a risk factor for CMV infection.

Diabetic mastopathy in an advanced elderly woman with insulin-dependent type 2 diabetes mellitus.

Diabetic mastopathy is an unusual stromal fibrotic lesion, but typically occurs in long-standing insulin dependent and younger diabetic patients. We report a case of diabetic mastopathy in an older diabetic patient. The patient was a 76-year-old woman with a history of type 2 diabetes mellitus for 13 years and 3 years of insulin treatment. She developed a 3 cm, hard, mobile nodule in the left breast. Mammography revealed a dense mass. Ultrasonography showed an irregular-shaped hypoechoic lesion with an unclear boundary and acoustic shadowing. Since fine needle aspiration biopsy delivered insufficient material and core needle biopsy did not yield any specific findings for diagnosis, clinically diabetic mastopathy was the prime suspect but breast cancer could be completely ruled out. Surgical excision was thus performed and diabetic mastopathy was confirmed pathologically. We report on this rare case of diabetic mastopathy in a 76 year-old type 2 diabetic patient.