Novel germline mutations in the APC gene of Cypriot patients with familial and sporadic adenomatous polyposis.

Familial adenomatous polyposis (FAP) is one of the two commonest familial syndromes that predispose to colorectal cancer. FAP is caused by mutations in the adenomatous polyposis coli (APC) tumour suppressor gene that has a high penetrance. The disease is characterized by the occurrence of hundreds to thousands of colorectal polyps, which if left untreated give rise to colorectal cancer. In Cyprus, there are no molecular data available as yet on families with FAP. This work presents the results of APC analysis in our population for the first time. The APC gene was analyzed in 33 DNA samples from 20 individuals belonging to four FAP families and 13 patients with sporadic polyposis. We identified three truncating mutations, four missense mutations and 11 polymorphisms. It is of interest that two of the three truncating mutations, 2307delA and Q1242X, are novel, which supports the existence of a unique genetic pool in the Cypriot population. This ethnic molecular study in addition to highlighting population heterogeneity also contributes to phenotype-genotype associations that are essential for the clinical management of FAP families in Cyprus.

Propranolol in the prevention of recurrent upper gastrointestinal bleeding in patients with cirrhosis undergoing endoscopic sclerotherapy. A randomized controlled trial.

The purpose of this study was to investigate the possible value of continuous administration of propranolol in the prevention of recurrent upper gastrointestinal bleeding in patients with cirrhosis undergoing chronic endoscopic sclerotherapy. Among 239 patients admitted for acute variceal bleeding, 85 with cirrhosis were randomized to receive sclerotherapy either alone (40) or in combination with propranolol (45). Sclerotherapy was carried out with an intravariceal injection of 5% ethanolamine oleate through a fiberoptic endoscope. The procedure was performed every week, until the esophageal varices at the gastroesophageal junction were too small for any further injections. Varices were reinjected if they recurred. Propranolol was given orally twice a day until heart rate was reduced by 25% in the resting position. The mean follow-up period was 23.2 and 24.2 months for sclerotherapy and the sclerotherapy plus propranolol groups, respectively. During this period a significant (P = 0.001) reduction in the recurrence of esophageal varices was observed in patients treated with the combination of sclerotherapy plus propranolol compared with those treated with sclerotherapy alone. However, the time of rebleeding from any source or from esophageal varices did not differ significantly between the two groups. In the sclerotherapy group 21 patients rebled (35 bleeding episodes) compared with 14 (22 episodes) in the combination therapy group. Patients in the sclerotherapy group were more prone to bleed from gastric varices and congestive gastropathy than patients treated with the combination of sclerotherapy plus propranolol (P = 0.012). Twenty-five patients in the endoscopic sclerotherapy group developed complications attributed to sclerotherapy compared with 23 patients in the sclerotherapy plus propranolol group. Complications directly attributable to propranolol were observed in 11 patients. Three of these patients stopped taking the drug due to heart failure (1) and flapping tremor (2). Eight patients (17.8%) died in the latter group while the corresponding figure in the sclerotherapy group was nine (22.5%). It is concluded that the continuous administration of propranolol may reduce incidences of recurrent upper gastrointestinal hemorrhage from gastric sources in patients with cirrhosis undergoing chronic sclerotherapy.

A prospective randomized trial comparing somatostatin, balloon tamponade and the combination of both methods in the management of acute variceal haemorrhage.

The aim of this study was to compare the efficacy of: (i) somatostatin infusion, (ii) balloon tamponade with the Sengstaken-Blakemore tube and (iii) the combination of both methods, in the management of acute variceal haemorrhage. Ninety-two consecutive patients with liver cirrhosis who proved to have active variceal bleeding on emergency endoscopy were studied. Thirty-one patients were randomly assigned to an intravenous infusion of 250 micrograms/h of somatostatin (Group I), 30 to the Sengstaken-Blakemore tube (Group II) and 31 to the combination of both methods (Group III). Somatostatin was administered for 24 h, while the gastric and esophageal balloons remained inflated for 48 and 24 h, respectively, then deflated. Patients were under observation for a further 24-h period after withdrawal of treatment. If bleeding recurred, the same treatment was repeated in each group. Following treatment the bleeding was controlled initially in 22 patients (71%) in Group I, in 24 (80%) in Group II and in 25 (80.6%) in Group III. In Group II a significantly (p less than 0.05) higher proportion of patients (14/24) rebled as compared to Groups I (5/22) and III (6/25). Bleeding was controlled following retreatment in four, ten and five patients of the three respective groups. There were marked differences, in the number of complications noticed with each form of therapy. Only three patients (9.7%) in Group I developed complications (p less than 0.05) as compared to ten (33%) in Group II and ten (32%) in Group III. Hospital mortality in all three treatment groups was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)