Targeted next generation sequencing screening of Lynch syndrome in Tunisian population.

A high colorectal cancer (CRC) incidence is observed in Tunisia, with a relatively high proportion of patients developing CRC before the age of 40. While this suggests a genetic susceptibility, only a few Tunisian Lynch Syndrome families have been described. In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients' tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenic MSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR, POLE and POLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected in MLH1 (n = 5) or MSH2 (n = 1). Two of six patients were from the same family and both were found to carry a novel in-frame MLH1 deletion, predicted to affect MLH1 function. All MLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germline MSH2 variant.

Unusual presentation of severely disseminated and rapidly progressive hydatic cyst: Malignant hydatidosis.

The infection caused by the tapeworm Echinococcus granulosus leads to the development of hydatic disease. It is the most frequent mediterranean parasitic infection that commonly affects the liver and rarely involves multiple organs. Herein, we report an exceptional and confusing presentation of hepatopulmonary and splenic hydatidosis due to Echinococcus granulosus that caused diagnostic problems occuring in a 70-year-old man, treated with chemotherapy, with favorable outcome. This was a very unusual case of disseminated hydatid cyst highlighting the interest of keeping a high level of clinical suspicion of this diagnosis every time we have a cystic lesion of the liver.

Appropiateness of colonoscopy in the university hospital center of monastir. Interest and applicability of criteria established by the European panel on the appropriateness of gastrointestinal endoscopy.

AIM: 1) To assess the applicability of EPAGE criteria in there first version (EPAGE I) in clinical practice, 2) to assess colonoscopy appropriateness using EPAGE I criteria, 3) to compare colonoscopy appropriateness and findings. METHODS: Four hundred and eighty-seven consecutive diagnostic colonoscopies were included. The appropriateness of the indication of colonoscopy was appreciated using a scoring system on the basis of the EPAGE criteria in there first version (EPAGE I). RESULTS: Appropriateness were applied in 86,4% of the colonoscopies. Fifty-one percent were appropriate, 14% uncertain and 18% inappropriate. The difference of 17% represented the procedures indicated for hematochezia and for witch an appropriateness score can not be attributed because of lack of clinical information. The probability of finding a clinically significant lesion was significantly higher in patients aged ≥ 50 years, males, inpatients, those referred by gastroenterologists and those who had the colonoscopy for "appropriate" indication according to the EPAGE I criteria. The independent variables correlated with the diagnostic yield of colonoscopy were the age, the appropriateness of indication and the health care setting. CONCLUSION: EPAGE I criteria were applicable in most patients and were correlated with significant findings. They are thereby useful to rationalize colonoscopy demand. However, they could be regularly updated.

[Serodiagnosis of acute hepatitis in adults patients: results of a prospective study in a central region of Tunisia]. / Sérodiagnostic des hepatitis aiguës de l'adulte: résultats d'une etude prospective dans une region du centre tunisien.

UNLABELLED: PRÉREQUIS: Viral hepatitis is a public health problem in many parts of the globe. In Tunisia, the respective responsibility of five viruses (HAV, HDV, HBV, HCV and HEV) in the genesis of acute hepatitis in adults is only roughly indicated in the absence of suitable serological studies, given as important to plan appropriate preventive strategies. OBJECTIVES: To approach the role of viral hepatitis in all adult with acute hepatitis, identify the current share of each virus A, B, C and E in the genesis of hepatitis and to study the epidemiological and evolution of these diseases. METHODS: We conducted a prospective study over two years including patients aged from 15 to 65 years old, with clinical and / or biological acute hepatitis. Data were collected through a standard questionnaire wich covered sociodemographic charactereristics and risk factors. Blood samples were collected and were tested for IgM anti-HAV, IgM anti-HEV, HBsAg, IgM anti-HBc, anti-HCV antibodies .When serological tests were negatives, further explorations including immunological test, search for HCV RNA and a pharmacovigilance survey was conducted. Statistical analysis was performed by SPSS version 10.0 RESULTS: 105 patients were included. Acute viral hepatitis was diagnosis in 70 patients (67%). The proportion of patients with acute viral hepatitis A, B, C and E was 51.5% , 38.5%, 4.3% and 5.7% respectively. The risk factors of viral hepatitis A was drinking of untreated water and poor socioeconomic status. In the HBV group, the notion of sexual contact risk was found in 30% of cases. The small numbers of acute hepatitis E and C does not permit us to draw conclusions. CONCLUSION: Our study confirms the shift in age of onset of hepatitis A to the age of adolescence and young adulthood. The respective responsibilities of the different viruses studied in the genesis of acute hepatitis in adults in our area brings us closer of western populations where HAV infection predominates followed by HBV.

[Epidemiological, clinical features, therapeutic results and evolution of gastrointestinal stromal tumour: about 25 cases]. / Caractéristiques épidémiologiques, cliniques, thérapeutiques et évolutives des tumeurs stromales digestives: à propos de 25 cas.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are mesenchymal tumors occuring in the majority of cases in the stomach and small intestine, rarely in rectum, colon, esophagus or mesentery. They are derived from cells of cajal or their precursor, and are typically CD117/KIT + (95%), CD34 + (70%). AIMS: is to study the epidemiological, clinical, therapeutic and evolution of gastrointestinal stromal tumors. METHODS: retrospective study including all patients with the diagnosis of GIST supported in the department of gastroenterology and surgery in universital hospital of Monastir. RESULTS: 25 patients were included, 12 men and 13 women with an average age of 60.5 years. Digestive symptomatology was dominated by gastrointestinal bleeding (n = 12) and abdominal pain (n = 12). The tumor was discovered incidentally in two patients. The small intestine was the most common site of the tumor (n = 10), followed by the stomach in 9 patients, rectum in two patients, the colon (n = 1), the bulb of water (n = 1), duodenum (n = 1) and liver in a patient. The tumor size ranged from 0.8 to 24 cm. GIST was localized in 16 patients, in whom therapeutic care based mainly on surgery and optimal broad. It was metastatic in 9 patients, in whom treatment using imatinib as first-line in 4 of them with a good response in 3 patients and the possibility of R0 surgery in one patient, initial stabilization and then a secondary exhaust in a patient. The first surgery was necessary in 5 patients in complicated situation or if diagnostic doubt. CONCLUSION: The best characterization of GIST thanks to advances in cancer research has led to improved treatment of these tumors. Surgery is the standard treatment in localized forms. Imatinib is the standard treatment in metastatic GIST first line as well as adjuvant after surgery.

[Plasma cholinesterase activity in hepatic diseases]. / Étude de l'activité de la cholinestérase plasmatique au cours des atteintes hépatiques.

Plasma cholinesterase activity (ChE) may vary in some pathological circumstances. We studied the changes in activity of this enzyme according to the type of liver injury, to assess the interest of this parameter in the diagnosis of liver diseases. Our study was performed on 102 patients with different liver diseases and 53 healthy controls. The ChE activity was lower in patients compared to control group (p < 0.0001), and more pronounced in cirrhotic patients compared to those suffering from hepatitis. Elevated activities of AST, ALT, GGT and ALP and bilirubinemia, and decreased albuminemia were noted in patients compared to controls (p < 0.001). Hypoalbuminemia was significantly important in cirrhotic patients compared to those suffering from cholestasis or hepatitis. A correlation between ChE and bilirubin, albumin and serum protein was found in patients with cirrhosis or those with chronic hepatitis. A significantly lower activity of ChE was found in patients with hepatic insufficiency (HI). In case of suspicion of HI, the prescription of ChE activity could guide or confirm the diagnosis of the impairment.

Managing the risk of cancer in Cowden syndrome: a case report.

INTRODUCTION: Cowden syndrome is a rare cancer predisposition syndrome inherited in an autosomal-dominant fashion. The syndrome is characterized by hamartomatous polyps that affect multiple organs: skin, mucous membranes, thyroid, breast, gastrointestinal tract, endometrium and brain. It is also associated with an increased risk of developing malignancy in many tissues but especially breast, thyroid and endometrium. CASE PRESENTATION: We present the case of a 30-year-old Tunisian woman with mental retardation who presented to our facility with rectal hamartomatous polyps. Her medical history included fibrocystic disease of the breast over the last three years. A physical examination revealed macrocephaly, hyperkeratotic papules on the mid-facial skin, palmoplantar keratosis and oral mucosal papillomatosis. A breast examination revealed nodular breast tissue bilaterally and a diffuse thyroid goiter. Our patient was clinically euthyroid. A total thyroidectomy was performed. A histopathologic examination revealed thyroid papillary carcinoma. A gastrointestinal evaluation revealed esophageal and gastric polyps. Biopsies showed hyperplastic and adenomatous lesions associated with Helicobacter pylori. A final diagnosis of Cowden syndrome was made according to the syndrome testing criteria adapted by the US National Comprehensive Cancer Network. A prophylactic bilateral mastectomy was proposed but refused by our patient. Our patient was kept under surveillance for breast and colorectal malignancies. CONCLUSIONS: Early and accurate diagnosis of Cowden syndrome is essential because it is a cancer predisposition syndrome that carries an increased risk for developing malignancy in many tissues, especially breast and thyroid. For this reason, education regarding the signs and symptoms of cancer is important. All patients must be screened for malignancies and options for prophylactic mastectomy should be discussed. Guidelines for cancer screening including surveillance and management plans for these patients should be distinguished from those of the general population, and may lead to a more timely diagnosis and treatment of cancers associated with this syndrome.

[Duodenal ulcer disease and Ramadan]. / Maladie ulcéreuse duodénale et Ramadan.

Ramadan fasting is accompanied by an increase of the gastric acidity over 24 hours especially in the daytime. Gastric acidity is maximal at the end of the fasting day. So, a patient with duodenal ulcer is exposed to a high risk of disease reactivation. The frequency of ulcer complications is statistically higher during the month of Ramadan than the rest of the year. The frequency of the upper gastrointestinal hemorrhage is multiplied by 2 and perforation by 4. Helicobacter pylori eradication does not seem to play a role in the occurrence of these complications, particularly the perforation. The patient with duodenal ulcer can fast without risks while using a proton pump inhibitor if the ulcer is healed and H. pylori is eradicated. Ramadan fasting seems to us inadvisable when duodenal ulcer is active, but large prospective studies are needed.

Clarithromycin versus metronidazole in first-line Helicobacter pylori eradication. Prospective randomized study of 85 Tunisian adults.

BACKGROUND: Although primary resistance to metronidazole remains high (56,8%), it is more widely used than clarithromycin as a firstline Helicobacter pylori (H. pylori) treatment in the common Tunisian practice. AIM: To compare the eradication rate in two protocols including clarithromycin versus metronidazole in Tunisian adults. METHODS: From July 2005 to December 2007, 85 patients aged 18 to 75 years presenting with gastro-duodenal lesions with H. pylori infection and requiring its eradication were included in the study. They were randomized to receive alternatively a seven-day triple therapy including: Omeprazole + Amoxicillin + Clarithromycin (OAC group) or Metronidazole (OAM group) twice a day. A second endoscopy with new biopsies was carried out 6 weeks after treatment to control eradication. RESULTS: Eighty five patients finished the protocol. The OAC and OAM groups included 46 and 39 patients respectively. They were comparable with respect to age, gender, clinical presentation and initial lesions. The total eradication rate was 60%. It was significantly higher in the clarithromycin group (69.6%) than in the metronidazole group (48.7%): p < 0.05. CONCLUSION: Clarithromycin is more effective than metronidazole in H. pylori eradication. It should be made available in our hospital's nomenclature. This would prevent iterative eradication courses and probably reduce treatment cost.

[Bowel preparation before colonoscopy]. / Préparation intestinale avant coloscopie.

Colonoscopy is a routinely performed procedure in adults. Completion of the procedure and proper visualization of the intestinal mucosa are highly dependent on the quality of the bowel preparation. The ideal bowel preparation should be safe, well-tolerated and effective. No bowel preparation method meets the ideal criteria for bowel-cleansing prior to colonoscopy. However, polyethylene glycol-electrolyte lavage solution and sodium phosphate are the most commonly used bowel preparations before colonoscopy and colon surgery. NaP preparations appear more effective and better tolerated than standard PEG solutions but should be administered with caution in patients with preexisting or at an increased risk for electrolyte disturbances. Timing and dose are important considerations regardless of the method used. The last generation of preparations improves safety and acceptability by reducing volume of liquid ingested.

[Hepatorenal syndrome]. / Le syndrome hépato rénal.

BACKGROUND: Hepatorenal syndrome (HRS) is a particular form of functional renal failure which may develop in patients with liver cirrhosis. Recent advances in the understanding of the biology of vasoactive mediators and the physiology of microcirculation have allowed to better anticipate its pathophysiological mechanisms. AIM: To review new advances in the knowledge of epidemiology, diagnosis criteria, pathophysiological mechanisms and treatment of HRS. METHODS: Review of literature using medical data bases (Medline) with the following key words: hepatorenal syndrome, pathophysiology, medical treatment, MARS, liver transplantation. RESULTS: During the course of cirrhosis, portal hypertension leads to splanchnic and systemic vasodilation, responsible for a reduction of effective arteriel blood volume. As a result, a state of intense renal vasoconstriction develops, leading to renal failure in the absence of any organic renal disease. At this stage, liver transplantation is the only definitive therapy able to reverse renal dysfunction. Pharmacologic and radiologic therapy is aimed at improving renal function to enable patients to survive until transplantation is possible. These therapies are based on vasoconstrictor drugs associated with intravenous albumin infusion and transjugular intrahepatic portosystemic shunt (TIPS). They improve circulatory function, normalize serum creatinine and may improve survival. CONCLUSION: Simple measures have been shown to reduce the risk of HRS in cirrhotic patients including the plasma volume expansion with albumin in patients with spontaneous bacterial peritonitis and optimal fluid management in patients undergoing large volume paracentesis.

[Role of Helicobacter pylori infection in iron deficiency anemia]. / Rôle de l'infection par l'Helicobacter pylori dans l'anémie ferriprive.

Anemia induced by digestive diseases refers to anemia due to iron deficiency. Conventional gastrointestinal diagnostic workup fails to establish the cause of iron deficiency in about one third of patients. Abnormal iron absorption is increasingly recognized as an important cause of unexplained iron deficiency. The importance of coeliac disease as a possible cause of iron deficiency anemia refractory to oral iron treatment, without other manifestations of malabsorption syndrome, is increasingly being recognized. In addition, Helicobacter pylori (HP) has been implicated in several recent studies as a cause of iron deficiency anemia (IDA) refractory to oral iron treatment. Cure of previously refractory IDA by HP eradication provides strong evidence supporting a cause-and-effect relationship. In order to establish a cause-and-effect relationship between HP gastritis and IDA, prospective randomized studies comparing the effects of iron administration with or without H. pylorieradication are highly recommended.

[Chronic viral hepatitis and kidney failure]. / Hépatites virales chroniques chez les patients insuffisants rénaux.

Chronic viral hepatitis remains a major problem among patients with chronic renal failure. Hepatitis B and C viruses are frequent among dialysis patients and after renal transplantation and may significantly diminish the survival of both the patient and the graft. Hepatitis B and C viral infection in these patients is often characterized by normal transaminase levels despite viremia and progressive liver lesions. Liver biopsy remains essential for assessing the extent of liver disease. Cirrhosis is a contraindication to transplantation of only a kidney, because of elevated morbidity and mortality. A combined as liver-kidney transplantation may be considered. The best treatment of hepatitis infections is preventive: vaccination against the hepatitis B virus and attentive hygiene, especially to prevent nosocomial transmission. Among patients not awaiting transplant, antiviral treatment should be reserved for patients with active or even fibrotic liver disease. For hemodialysis patients awaiting kidney transplant: Alpha interferon is ineffective and poorly tolerated by dialysis patients. Lamivudine is effective and well tolerated, but its long-term efficacy and its optimal effective dose in dialysis patients remain unknown.