CTLA4 gene polymorphism in Italian patients with colorectal adenoma and cancer.

BACKGROUND AND AIMS: Colorectal cancer is a major health problem. Colonoscopic colorectal cancer screening is cumbersome and expensive. Identification of genetic risk of colorectal cancer may help to select the subjects who could benefit from colonoscopy. The immune system plays a fundamental role in the human-environment interaction, and the carcinogenic effects of many environmental factors are mediated by the chronic activation of the immune system in a genetic-controlled fashion. Cytotoxic T lymphocyte associated antigen 4 (CTLA4) plays an inhibitory role in regulating lymphocyte functions. The loss of CTLA4 function is responsible for loss of mucosal lymphocyte tolerance. The G allele at position +49 of exon 1 of the CTLA4 gene affects the CTLA4 function. We evaluated in an association study the role of CTLA4 A+49G polymorphism as a risk factor for colorectal neoplasm. PATIENTS AND METHODS: Five hundred and fifty-six patients (male 295; female 261) who underwent colonoscopy at our Centre were enrolled in the study and divided into three groups: Colorectal cancer (132 patients, M/F 68/64, mean age 66+/-11 years); Colorectal adenoma (186 patients, M/F 110/76, mean age 65+/-11 years); Healthy controls (238 patients, M/F 117/121, mean age 63+/-10 years). DNA was extracted from peripheral blood, CTLA4 gene was amplified by using specific primers, and A+49G polymorphism was analysed by restriction enzyme digestion. RESULTS: No statistically significant differences in the genotype distribution among Control and Adenoma groups (p=0.93), Control and Carcinoma groups (p=0.52), and Adenoma and Carcinoma groups (p=0.53) were observed. CONCLUSION: There is no significant correlation between CTLA4 A+49G polymorphism and the risk of colorectal neoplasm among Italian Caucasians.

Osteoporosis: still a typical complication of primary biliary cirrhosis?

BACKGROUND: Osteoporosis is a recognized complication of primary biliary cirrhosis but it has been suggested that its prevalence may overlap that observed among postmenopausal women. AIM: To evaluate prevalence and risk factors of osteoporosis in primary biliary cirrhosis. PATIENTS: A total of 133 female patients (age 53+/-10 years, menopausal status 70%, histological stage I-II 61%, portal hypertension 28%, Mayo Risk Score 4.11+/-0.59) were enrolled. METHODS: Dual X-ray absorptiometry of the lumbar spine. RESULTS: Mean bone mineral density, T and Z score were 0.861+/-0.160 g/cm2, -1.87+/-1.45 and -0.78+/-2.63, respectively. At multivariate analysis, bone mineral density was inversely correlated with age (p<0.05). Osteoporosis was present in 39/92 (41%) postmenopausal and 8/41 (20%) premenopausal patients. In the premenopausal group, osteoporosis was significantly correlated with serum albumin (p<0.05) and Mayo Risk score (p<0.005). No significant correlation was present in the postmenopausal group. CONCLUSIONS: Despite the accepted wisdom that osteoporosis is a common complication of primary biliary cirrhosis, its frequency in post-menopausal patients overlaps that observed in the general population, but is much more frequent in premenopausal patients, where it appears to be related to severity of liver disease and cholestasis.

Achalasia.

AIM: Achalasia is a disease of unknown etiology resulting from degeneration of the esophageal Auerbach submucous plexus. This degeneration makes normal relaxation of the cardia during swallowing impossible leading to dysphagia, chest pain and regurgitation of varying degree. Until 15 years ago the main conservative treatment for achalasia was dilatation of the cardia with the Starck apparatus. Such approach to achalasia was usually reported as fairly effective, but complicated by an exceedingly high rate of perforation. This led most centers to replace the Starck procedure with pneumatic or hydrostatic balloon dilators. The aim of our study was to evaluate safety, early and late results of the Starck procedure. METHODS: Our report is based on the retrospective analysis of 21 patients [male/female: 12/9, mean age 46 years (range-65)] who underwent 52 Starck procedures for esophageal achalasia. The effectiveness of the Starck procedure was assessed according to the scale of Vantrappen and Hellemans. RESULTS: After the scheduled 2 Starck sessions, an excellent result was seen in 10 patients (50%), a good result in 8 (40%); 2 patients (10%) showed a poor result. One month after the last Stark procedure 1 patient (5%) experienced gastroesofageal reflux easily managed with protein pump inhibitors. During or after dilations no major complications were observed. CONCLUSIONS: The Starck procedure, now replaced by the new Rigiflex pneumatic dilator, resulted effective and safe in experienced hands.

Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders.

BACKGROUND AND AIMS: Duration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (> or = 16 years). METHODS: We screened for the presence of autoimmunity in 605 controls (16-84 years) and 422 patients (16-84 years), all of whom had been on gluten withdrawal for at least one year (median follow up 9.5 years). A logistic regression analysis, setting the prevalence of autoimmunity as the dependent variable, was employed to control for independent covariates as predictors of the risk of autoimmunity. RESULTS: The prevalence of autoimmunity was threefold higher (p < 0.00001) in patients than in controls. Mean duration of gluten exposure was 31.2 and 32.6 years for patients with or without autoimmunity. Logistic regression showed that increased age at diagnosis of coeliac disease was related to the prevalence of autoimmune disease while "actual gluten exposure" which takes into account diet compliance, follow up, and age at diagnosis of autoimmune disorders were not predictive for the risk of developing autoimmune diseases (odds ratio 0.82 per year). CONCLUSION: The prevalence of autoimmune diseases in patients with a late coeliac disease diagnosis does not correlate with duration of gluten intake. Early exposure to gluten may modify the immunological response. Gluten withdrawal does not protect patients with a late diagnosis from autoimmune diseases.