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.

Surgery for Colorectal Cancer in Elderly Patients: How Could We Improve Early Outcomes ?

BACKGROUND: Age is one of the causes behind the undertreatment of elderly colorectal cancer patients. The increase of mortality among elderly colorectal cancer (CRC) patients is due to competing causes of death occurring in the early post operative period. The purpose of this study was to evaluate the risk factors for post operative mortality and morbidity among elderly CRC patients. MATERIALS AND METHODS: A retrospective descriptive chart review was performed on consecutive patients older than 70 y with CRC. We have collected data of 124 patients who were admitted from January 2001 to January 2010. Demographic characteristics, operative and postoperative informations were retrospectively analysed. RESULTS: Early postoperative morbidity, operation related to morbidity and mortality were observed in 44 (35.5%), 9 (7.3%) and 20 (16.1%) cases, respectively. No other factors but ASA score (p = 0.002 and 0.005 in univariate and multivariate analyses, respectively) and emergency operations (p<0.001 and 10(-3) in univariate and multivariate analyses, respectively), were found to be risk factors of mortality. The results of multivariate analyses indicated that anaemia (p=0.021) and rectal cancer (p=0.015) had significant impact on the risk of anastomotic leakage. On the other hand, diabetes mellitus and rectal cancer were indicators that correlated with the width of hospitalization. CONCLUSION: Elderly CRC patients should no longer be undertreated only because of their age. They should be exposed to more aggressive management than they are currently receiving. Careful preoperative evaluation, followed by medical optimization and planning of perioperative care could improve outcomes of colorectal surgery for elderly patients.

Clinico-Pathological Caracteristics, Therapeutic Features and Post-operative Course of Colorectal Cancer in Elderly Patients.

STATEMENT OF PROBLEM: Colorectal cancer is predominantly a disease of elderly people and is a major cause of morbidity and mortality in the elderly population. The geriatric colorectal population is a very heterogeneous group, including patients with excellent health status and others with comorbid conditions, functional dependency, and limited life expectancy. On the other hand, the effectiveness of surgery for colorectal cancer depends on it being carried out safely, which allows most patients to return to productive lives, with an improved post-operative life expectancy or at least one that is not diminished by the surgery. MATERIALS AND METHODS: This work is a descriptive study of a retrospective cohort, based on administrative databases, of all patients with colorectal cancer diagnosed or treated in our institution. We extracted data on sociodemographic characteristics, comorbidity, type of cancer, stage of cancer, type of treatment received, post-operative complications and cause of post-operative death. We compared differences between an elderly group (Group A) (age >75 years) and a group of patients below 75 years (Group B). RESULTS: We found that elderly patients with colorectal cancer were more likely to be operated in emergent conditions, had more non-specific complications and more post-operative mortality than patients below 75 years. On the other hand, tumours stages, tumours characteristics and post-operative specific morbidity have been proved to be similar, both in Group A and Group B patients. CONCLUSION: These results suggest that surgery is feasible and can be safe for patients above 75 years, but it needs much more evaluation of comorbidities, pre- and post-operative intensive care to avoid post-operative non-specific complications.

Hepatitis B virus and hepatitis C virus co-infection: a therapeutic challenge.

Hepatitis B virus and hepatitis C virus are the two most common causes of chronic liver disease in the world. Dual infection with hepatitis B virus and hepatitis C virus, whose prevalence is underestimated, is characterized by a more severe liver injury, a higher probability of liver cirrhosis and a higher incidence of hepatocellular carcinoma. Treatment of these patients represents a therapeutic challenge. We report the case of an hepatitis B virus-hepatitis C virus co-infected patient, which particularly illustrates the interactions between these two viruses and therapeutic problems caused by the dual infection. HCV was initially dominant, which indicated a combination therapy by pegylated interferon and ribavirin. This treatment was associated with an early virological response of the HCV but an increase of HBV DNA occurred, requiring the use of a nucleoside analogue. A good response was obtained for the HBV but a relapse of HCV was noted, posing a problem for therapeutic decision.

Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient.

Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of immunomodulator therapy in a human immunodeficiency virus-negative heterosexual man.

Gastrointestinal bleeding due to an erosion of the superior mesenteric artery: an exceptional fatal complication of pancreatic pseudocyst.

The erosion of a pancreatic pseudocyst into an adjacent artery is a rare and highly lethal complication of pancreatitis with reported death rates of 12% to 40%. The majority of patients had bleeding from the splenic artery, the gastroduodenal artery and the anterior pacreaticoduodenal artery. Exceptionally, some cases with bleeding from the superior mesenteric artery, or hepatic artery were reported. We report the case of a 50 year old patient having a cataclysmic upper gastrointestinal bleeding due to an erosion of the superior mesenteric artery by a pancreatic pseudocyst, and discuss contemporary methods in diagnosis and management of the condition.

Frequency and clinical significance of core promoter and precore region mutations in Tunisian patients infected chronically with hepatitis B.

Genetic variability of hepatitis B virus (HBV) in the C gene and its association with the different stages of chronic liver disease has been studied inadequately with controversial results. The objectives of the current study were to determine the frequency of core promoter and precore mutations in chronic hepatitis B in Tunisia and to evaluate their impact on viral replication and disease progression. Sequencing was performed in upstream regulatory sequence (URS), pre-core (PreC) and basal core promoter (BCP) regions for 123 chronic infected patients by HBV genotype D at different status of disease. Mutations were detected in 98.4% of cases, affecting URS, BCP and Pre-C in 95.1%, 95.9% and 87.8% respectively. Multi-mutations increased significantly from asymptomatic carrier to advanced liver disease status. G1896A (74.8%), G1764A/T/C (71.5%), G1899A (54.4%) and T1678C (52%) were the most common. Special attention should be paid to A1703T, T1678C/G-A1703T, and A1652G-A1679G mutations probably specific of Tunisians sequences; they were observed in 40.6%, 41.5% and 30.1% respectively. A1679G/C, T1753C/G/A, A1762T/G and A1762T-G1764A were more prevalent in older patients. High DNA levels were associated with G1899A or G1764T/C-C1766G-C1799G and advanced liver disease with mutations at positions 1762, 1764 and/or 1899 alone or in double or triple mutations. It was also shown that substitutions at nucleotides 1762, 1764 and 1899 have an impact on the disease progression. It is the first report for specific mutations in the URS region for genotype D. It should be completed by studying eventual correlation with clinical progression and the response to treatment.

Histopathologic characteristics and short-term outcomes of colorectal cancer in young Tunisian patients: one center's experience.

INTRODUCTION: Colorectal carcinoma (CRC) is generally a disease of persons older than 40 years. Concerning younger patients, controversies still exist regarding features and prognosis of CRC. We performed this study to characterise CRC in young patients (≤ 40 years) as well as to evaluate short-term outcome in comparison with older patients (>40 years) with CRC. METHODS: Clinical and histopathological parameters of 40 patients aged 40 years or less were compared with 240 patients aged more than 40 years. RESULTS: In young patients, the minority suffered from hereditary cancer syndromes (0.4%). Furthermore, up to 87% of young patients denied any cancers in their families. Compared with older patients, young patients had more mucinous adenocarcinomas (32.5% vs. 11.5%; p=0.02), more venous invasion (p=0.021), more perineural invasion (p=0.028). For grading (p=0.42), lymphatic invasion (p=0.17) and tumor sites (p=0.46), no significant differences between young and older patients were found. Young patients had less post operative morbidity (p=0.039), less post operative mortality (0.029). Young and older patients had the same overall 1-year survival rates (p=0.24), and the same cancer-related 1-year survival rates (p=0.1). CONCLUSION: Tunisian patients present with colorectal cancer at a more advanced stage of the disease at younger ages compared to developed countries. The early detection of CRC followed by a sufficient oncologic treatment is crucial regardless of age. It is mandatory for all patients with suspicious symptoms to undergo early adequate diagnoses.

Solid pseudopapillary neoplasm of the pancreas in an old man: age does not matter.

Solid pseudopapillary tumor (SPN) of the pancreas is a rare tumor, but has favorable prognosis. It is typically observed in young women. Only few cases have been reported in young men. We report the observation of a 73-year-old man presented with a palpable mass in the left upper abdomen. CT scan showed 10 cm mass at the tail of the pancreas. This mass had mixed cystic and solid components. The patient underwent a distal pancreatectomy and splenectomy. SPN of the pancreas was diagnosed based on histopathological features. The patient recovered uneventfully and didn't receive adjuvant therapy. A CT scan performed 16 months postoperatively showed no evidence of disease recurrence. Although SPN of the pancreas is typically observed in young women, the diagnosis should not be discounted in old male patients. Male patients and those with old age, atypical histopathology and incomplete resection may have a higher risk of recurrence and death, deserving particular attention.

[Prevalence of the microscopic colitis to the course of the chronic diarrhea: about 150 cases]. / Prevalence de la colite microscopique au cours des diarrhees chroniques: à propos de 150 cas.

The goal of our survey is to value the microscopic colitis frequency at 150 patients, colliged on a period of 6 years (1997-2003), that have a chronic diarrhea with a normal total coloscopy and that benefitted of systematic biopsies. The microscopic colitis has been recovered at 44 patients on 150 either 29.3%. 16 of our patients (37%) are put on Salazopyrine, they answered well to the treatment with a receding of 3 years. The microscopic colitis is a pathology whose frequency seems under valued, it is certainly benign but can give a frequent diarrhea requiring a curative treatment.