c.1227_1228dupGG (p.Glu410Glyfs), a frequent variant in Tunisian patients with MUTYH associated polyposis.

INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal dominant-inherited disease caused by germline variants in the APC gene. It is characterized by the development of hundreds to thousands of adenomatous polyps in colon and rectum. Recently, biallelic germline variants in the base excision repair (BER) gene: MUTYH have been identified in patients with attenuated FAP and/or negative APC result. It can be responsible for an autosomal recessive inherited colorectal cancer syndrome (MAP syndrome: MUTYH-associated polyposis). OBJECTIVE: The aim of this study was to evaluate germline variants of MUTYH gene in Tunisian patients with attenuated FAP. METHODS: thirteen unrelated patients from Tunisia with attenuated FAP were screened for MUTYH germline variants. Direct sequencing was performed to identify point variants in this gene. RESULTS: A Biallelic MUTYH germline variant were found in all patients and showed an attenuated polyposis phenotype almost of them without extra-colic manifestations: The known pathogenic frameshift variant c.1227_1228dupGG (p. Glu410Glyfs) was found, in homozygous state, in 13 index patients. CONCLUSION: Patients with attenuated familial adenomatous polyposis (<=100) and no obvious vertical transmission of the disease should be considered for MUTYH gene testing.

The natural history of hepatitis B virus cirrhosis after the first hepatic decompensation in Tunisia.

AIM: To define the natural long term course of viral B cirrhosis after the onset of hepatic decompensation and to determine the predictive factors of death. METHODS: Retrospective longitudinal study including 77 cases of viral B cirrhosis among 192 consecutive patients with cirrhosis, hospitalized between 1997 and 2005 for the first hepatic decompensation. All those patients were followed- up until death or until December 2006. The probability of survival after the first hepatic decompensation was calculated using the Kaplan Meier method. The predictive factors of death were determined through univariate and multivariate analyses with the Cox regression model. RESULTS: Fifty four men and 23 women with an average age of 54±14.9 years were hospitalized for the first decompensation of the viral B cirrhosis. The 77 patients had been under observation for an average period of 24.2 ±21.1 months. During that time 64% among them died. The probability of survival after decompensation was 47% in 2 years and 22 % in 5 years. During follow- up, ascites was the most frequent decompensation (85%) followed by hepatic encephalopathy (38 %), variceal hemorrhage (34 %), jaundice (30%), hepato renal syndrome (27%), hepatocellular carcinoma (21%), and spontaneous bacterial peritonitis (14%). At univariate analysis four factors were predictive of death: Child Pugh C score (p=0.009), hepatocellular carcinoma (p=0.01), rate of serum gammaglobulin superior to18g / l (p=0.008) and prothrombin time inferior to 50 % (p=0.02). According to the multivariate analysis only the rate of serum gammaglobulin superior to 18g /l was an independent predictive factor of mortality (p=0,001) with IC (95 %) [1.623 - 5.88]. CONCLUSION: In Tunisia, the prognosis of viral B cirrhosis after the first decompensation is bad, because a patient on 5 only was able to survive beyond 5 years. Ascites is the most frequent decompensation. Only the rate of serum gammaglobulin superior to 18g / l is an independent predictive factor of mortality.

[Utility of immunohistochemistry in detecting alterations of mismatch repair genes of DNA. A series of 48 cases of colorectal cancer]. / Utilité de l'immuno-histochimie dans la détection des altérations des gènes réparateurs des mésappariements de l'ADN À propos d'une série de 48 cas de cancers colorectaux.

Hereditary non-polyposis colorectal cancer (HNPCC) is associated in more than 95% to a germline mutation in the genes of the mismatch repair (MMR) of DNA. The aim of this study was to assess the utility of immunohistochemistry, a simple and fast technique, in the triage of families where HNPCC is suspected. Tumor samples included in this study were from patients with resection for colorectal cancer, examined in our laboratory between 2004 and 2007. For each case, a formalin-fixed paraffin-embedded tissue block containing tumor tissue and normal adjacent mucosa was selected. Tumor specimens were examined with immunohistochemistry for the presence of hMLH1, hMSH2, and hMSH6 proteins. Scoring of the tumor staining was performed without any knowledge of patients' family history. The loss of protein expression was noted in four patients among 48 cases tested: two cases with isolated loss of hMSH2, a case with isolated loss of hMSH6 and one case with combined loss of MSH2/MSH6. No case has shown a suppression of hMLH1 protein. Comparing the immunohistochemical results for clinical has revealed a clear correlation between loss of protein expression demonstrated by immunohistochemistry and clinical data. Indeed, three cases among the four who showed no expression of MMR proteins showed at least one clinical criterion predictive of HNPCC. In conclusion, our study support the potential utility of immunohistochemistry to identify a significant portion of colorectal tumors derived from germline mutation of MMR genes and can be used as an adjunct measure in the identification of HNPCC.

Variceal band ligation in the prevention of variceal bleeding: a multicenter trial.

BACKGROUND/AIM: Variceal bleeding is a life-threatening complication of portal hypertension with a high probability of recurrence. Treatment to prevent first bleeding or rebleeding is mandatory. The study has been aimed at investigating the effectiveness of endoscopic band ligation in preventing upper gastrointestinal bleeding in patients with portal hypertension and to establish the clinical outcome of patients. PATIENTS AND METHODS: We analyzed in a multicenter trial, the efficacy and side effects of endoscopic band ligation for the primary and secondary prophylaxis of esophageal variceal bleeding. We assigned 603 patients with portal hypertension who were hospitalized to receive treatment with endoscopic ligation. Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The primary end point was recurrent bleeding. RESULTS: The median follow-up period was 32 months. A total of 126 patients had recurrent bleeding. All episodes were related to portal hypertension and 79 to recurrent variceal bleeding. There were major complications in 51 patients (30 had bleeding esophageal ulcers). Seventy-eight patients died, 26 deaths were related to variceal bleeding and 1 to bleeding esophageal ulcers. CONCLUSIONS: A great improvement in the prevention of variceal bleeding has emerged over the last years. However, further therapeutic options that combine higher efficacy, better tolerance and fewer side effects are needed.

[The particularity of Helicobacter pylori chronic gastritis in the west center of Tunisia]. / Les particularités de la gastrite chronique a Hélicobacter pylori au centre ouest de la Tunisie.

BACKGROUND: The Helicobacter pylori (HP) is strongly associated with chronic gastritis. The aim of our study was to determine prevalence of the HP chronic gastritis in the west center of Tunisia and to clarify the clinical and the histological particularities of this infection. METHODS: it is a prospectif study carried out from September 2002 to July 2005 and had included 352 patients. All the patients had an upper endoscopy in which five gastric biopsies were taken for a histological study. The biopsy specimens were fixed in 10% buffered formol and then included in paraffin. The specimens were cut at 4 microm and stained with Hematoxyline Eosine, modified Giemsa and Alcian bleu SAP. The histological examination revealed HP specimens, the lymphoplasmocytic infiltration, the gastritis activity, the gastric atrophy and the intestinal metaplasia according to Sydney system. RESULTS: They were 162 men and 190 women,with a mean age of 48.3 years. The erythematous antral gastritis was the most frequent at endoscopy (26.7%). The prevalence of HP chronic gastritis was 89% in patients with endoscopic lesions. The activity of the gastritis was 89.7% in the antrum and 52.2% in the fundus. The activity mean score in the antrum was 2, 1.8 and 0.3 respectively in the case of duodenal ulcer and gastric adenocarcinoma vs 0.68, 1.1 and 0.16 in gastric fundus. The prevalence of gastric atrophy was 35%. The atrophy was found in the antrum in 98% of cases. The prevalence of intestinal metaplasic was 11%. CONCLUSION: the HP chronic gastritis is very frequent in the west center of Tunisia. Its prevalence is found elevated since the adolescence. It predominate the gastric antrum. It is often associated with a duodenal ulcer rather than gastric cancer.

Gemcitabine plus oxaliplatin for patients with advanced hepatocellular carcinoma using two different schedules.

BACKGROUND: New therapies are needed to improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). Various gemcitabine-oxaliplatin combinations have been tested recently in patients with ovarian and pancreatic carcinoma, yielding interesting results with little toxicity. Therefore, the authors evaluated the activity and toxicity of two such combinations in patients with HCC. METHODS: Twenty-one patients were enrolled prospectively in the study. Eleven patients received gemcitabine 1000 mg/m2 on Day 1 and oxaliplatin 100 mg/m2 on Day 2 (GEMOX-1), and 10 patients received gemcitabine 1500 mg/m2 on Day 1 followed by oxaliplatin 85 mg/m2 on Day 1 (GEMOX-2). Treatment was repeated every 2 weeks until disease progression developed or until unacceptable adverse effects occurred. RESULTS: All patients were assessable for response and toxicity. Four patients (19%) achieved objective responses (95% confidence interval, 13-26%), including 3 patients in the GEMOX-1 group and 1 patient in the GEMOX-2 group. Ten patients (48%) had stable disease, and 7 patients (33%) experienced disease progression. The median progression-free survival was 5 months, and the median overall survival was 12 months. Fifty-four percent of patients in the GEMOX-1 group and 50% of patients in the GEMOX-2 group had received previous systemic chemotherapy or cisplatin-based chemoembolization. Grade 3-4 hematologic toxicity, according to National Cancer Institute Common Toxicity Criteria, consisted of thrombocytopenia (GEMOX-1 vs. GEMOX-2, 18% vs. 40%) and neutropenia (0% vs. 30%). No Grade 3-4 nonhematologic toxicity was observed, except for 1 episode of Grade 3 diarrhea. Grade 1 neurotoxicity and Grade 2 neurotoxicity (specific scale), respectively, were observed in 4 patients and 7 patients receiving GEMOX-1 and in 7 patients and 1 patient receiving GEMOX-2. CONCLUSIONS: Gemcitabine-oxaliplatin combination therapy is feasible in patients with advanced HCC. The GEMOX-1 regimen was tolerated better than the GEMOX-2 regimen. Currently, the GEMOX-1 regimen is being evaluated in a Phase II study in previously untreated patients with HCC.