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.

Controlled trial of oral 5-aminosalicylic acid for the prevention of early relapse in Crohn's disease.

BACKGROUND: Recent data indicate that 5-aminosalicylic acid (5-ASA) is most effective in preventing relapse of Crohn's disease in patients with a short duration of remission before enrollment. AIM: To evaluate the efficacy of oral 5-ASA treatment, started immediately after achieving steroid-induced remission, in preventing clinical relapses of Crohn's disease. METHODS: Patients with active Crohn's disease, achieving remission on steroids, were randomized to oral 5-ASA 3 g/day or placebo, while steroids were tapered over 6 weeks. The trial was terminated after interim analysis showed a slightly higher relapse rate in the 5-ASA group, and the calculated probability of seeing a statistically significant difference by completing the study was minimal. RESULTS: Final analysis included 117 patients (58 taking 5-ASA and 59 taking placebo; follow-up 9.2 +/- 6.5 months). Cumulative relapse rates at 6 and 12 months were 34% and 58% in 5-ASA patients and 31% and 52% in placebo patients, respectively (rate difference +0.095; 95% CI = -0.085 to +0.274). Subgroups analysis showed that 5-ASA was equally ineffective in patients with ileal, colonic or ileocolonic disease. CONCLUSIONS: Contrary to previous results, in our study early introduction of treatment with oral 5-ASA did not prevent relapse in Crohn's disease patients treated with steroids to induce remission.

Vertebral osteopenia due to bone marrow hyperplasia during interferon-alpha and ribavirin therapy for chronic hepatitis C.

We report the magnetic resonance imaging of a severe, but fully reversible, vertebral osteopenia, due to bone marrow hyperplasia, occurring in a patient with chronic hepatitis C treated with the interferon-alpha/ribavirin combination.

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.

[Prognostic value of nuclear morphometry in follicular carcinoma of the thyroid gland]. / Valore prognostico della morfometria nucleare nel carcinoma follicolare della tiroide.

Histological material from 60 cases of follicular carcinoma of the thyroid operated between 1962 and 1987 was examined morphometrically to see whether this would produce data that could be correlated with survival. Nuclear parameters (area, perimeter, minimum and maximum diameter and their ratio, form factor) and the mitotic index were investigated. At the same time, account was taken of certain clinical parameters (sex, age, degree of differentiation, size of the primary lesion, extension of the tumour) potentially correlated with prognosis. Survival in relation to all these variables was examined by means of an actuarial method and subjected to both uni- and multivariate analysis. The results, although suggesting the existence of a relationship between nuclear size and the aggressiveness of this type of tumour, failed to demonstrate a significant correlation between these morphometric parameters and survival after treatment. By contrast, survival was significantly influenced by some of the clinical variables, particularly loco-regional extension of the disease and the patient's age. The prognostic significance of nuclear size was recently demonstrated in breast cancer and in a series of thyroid carcinomas including tumours with different morphologies and progression patterns. In follicular thyroid carcinoma the degree of cellular pleomorphism is usually low. So, morphometry does not seem able to provide information regarding prognosis more valuable than those obtained by the clinical data.

[Prognostic value of nuclear morphology in colorectal neoplasms]. / Valore prognostico della morfologia nucleare nelle neoplasie del colonretto.

Cytomorphometry measures the main geometric parameters of the cell nucleus (area, min. and max. diameter, circunference) on ordinary histological preparations. It has been employed to asses the prognosis of breast and ovary tumours. The possibility that cytomorphometry, when allied with other parameters, such as age, sex, Duke's stage, bleeding etc., can be used in the prognosis of tumours of the large intestine is examined through a study of intraoperative biopsies from 44 patients followed after surgery. Univariate analysis showed that the Duke's stage and tumour site were significantly related to prognosis. The standard deviation of the maximum diameter and circunference were also related to survival with a negative correlation. Multivariate analysis confirmed the significance of the maximum diameter and the Duke's stage. These parameters were then used to calculate the relative risk. If due account is taken of the reservation expressed in the literature concerning the reproducibility of the data offered by cytomorphometry and its heavy dependence on the skill of the operator, it can be used to advantage in the prognosis of the colorectal tumours.