Mohamed Cherif

Smoking and Polymorphisms in Xenobiotic Metabolism and DNA Repair Genes are Additive Risk Factors Affecting Bladder Cancer in Northern Tunisia

Cancer epidemiology has undergone marked development since the nineteen-fifties. One of the most spectacular and specific contributions was the demonstration of the massive effect of smoking and genetic polymorphisms on the occurrence of bladder cancer. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). DNA repair is essential to an individual’s ability to respond to damage caused by tobacco carcinogens. Alterations in DNA repair genes may affect cancer risk by influencing individual susceptibility to this environmental exposure. Polymorphisms in NAT2, GST and DNA repair genes alter the ability of these enzymes to metabolize carcinogens or to repair alterations caused by this process. We have conducted a case-control study to assess the role of smoking, slow NAT2 variants, GSTM1 and GSTT1 null, and XPC, XPD, XPG nucleotide excision-repair (NER) genotypes in bladder cancer development in North Tunisia. Taken alone, each gene unless NAT2 did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotypes, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk to develop bladder cancer (OR = 7.14; 95% CI: 1.30–51.41). However, in tobacco consumers, we have shown that Null GSTM1, Wild GSTT1, Slow NAT2, XPC (CC) and XPG (CC) are genetic risk factors for the disease. When combined together in susceptible individuals compared to protected individuals these risk factors give an elevated OR (OR = 61). So, we have shown a strong cumulative effect of tobacco and different combinations of studied genetic risk factors which lead to a great susceptibility to bladder cancer.

Incidence and Risk Factors for Post–Renal Transplant Diabetes Mellitus

INTRODUCTION Posttransplant diabetes mellitus (PTDM) is a common, serious complication of renal transplantation. The aim of this retrospective study was to estimate the incidence and to identify potential factors predisposing to PTDM. PATIENTS AND METHODS We evaluated 296 adult nondiabetic patients who underwent kidney transplantation at our center. PTDM was defined according to 2003 international consensus guidelines. Potential factors predisposing to PTDM were analyzed individually and simultaneously using a logistic regression model. RESULTS Over 2054.5 years of cumulative follow-up, 51 patients (17.2%) developed diabetes corresponding to an annual incidence of 2.5%. PTDM was diagnosed after a median of 2.9 months (range: 0.2-168). The mean age of affect individuals was 33.3±7.4 years. Patients with PTDM were significantly older (P<.0005) and showed an higher body mass index (BMI; P<.004). Univariate analysis revealed that age, BMI, family history of diabetes, vascular nephropathy, and hepatitis C infection were associated with PTDM. Multivariate analysis rescaled the roles of age (relative risk [RR]=1.046/y; P<.04), BMI (RR=1.107/kg/m2, P<.05), vascular nephropathy (RR=7.06, P<.03), and hepatitis C infection (RR=2.72, P<.03) as independent factors predisposing to PTDM. CONCLUSION Among our relatively young kidney transplant recipients, in whom only 8% received tacrolimus, PTDM was a frequent complication. We suggest that the use of oral glucose tolerance tests to screen patients identifies those predisposed to develop this complication.

Smoking and polymorphisms in folate metabolizing genes and their effects on the histological stage and grade for bladder tumors.

Folates are the common sources of DNA synthesis and methylation. Cigarette smoking and genetic susceptibility of folate enzymes are two suspected factors most closely associated with bladder cancer development. This study sought to determine the effect of smoking and genetic polymorphisms in folate metabolizing enzymes on the histological stage and grade of bladder tumors in Tunisian patients. A total of 130 patients with urothelial cell carcinomas were examined with respect to smoking status, MTHFR (5,10-methylenetetrahydrofolate reductase), MTR (methionine synthase), MTRR (methionine synthase reductase) and TYMS (thymidylate synthase) genotypes distribution. Our data have reported that tobacco, MTHFR, MTR and MTRR genotypes were not associated with bladder tumor stage. Only TYMS 3R*G/3R*C genotype was associated with increased risk of developing invasive tumors compared to reference group (RR = 1.74; 95% CI: 0.97-3.12). When we studied the superficial bladder tumor group, we have shown a significant statistical differences for the TYMS 3R*G/2R genotype. This genotype presented a 1.68-fold increased risk of developing high grade tumors compared to reference group (RR = 1.68; 95% CI: 1.12-2.54). Moreover, we have shown that patients having at least one copy of 2R allele were at 4.23-fold increased risk for developing high grade tumors compared to reference group (P = 0.022).

In vivo prevention of bladder urotoxicity: purified hydroxytyrosol ameliorates urotoxic effects of cyclophosphamide and buthionine sulfoximine in mice.

Urotoxicity is a troublesome complication associated with cyclophosphamide (CP) and L-buthionine-SR-sulfoximine (BSO) treatment in chemotherapy. With this concern in mind, the present study investigated the potential effects of a hydroxytyrosol extract from olive mill waste (OMW) on urotoxicity induced by acute CP and BSO doses using a Swiss albino mouse model. Toxicity modulation was evaluated by measuring lipid peroxidation (LPO) and antioxidants in urinary bladder. The findings revealed that the hydroxytyrosol extract exerted a protective effect not only on LPO but also on enzymatic antioxidants. When compared to the controls, the CP-treated animals underwent significant decreases in the glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GP), and catalase (CAT) activities. The level of glutathione (GSH) was also reduced with increased doses of LPO in the CP-treated animals. L-Buthionine-SR-sulfoximine treatment exerted an additive toxic effect on the CP-treated animals. Interestingly, pretreatment with the hydroxytyrosol extract restored the activities of all enzymes back to normal levels and exhibited an overall protective effect on the CP- and BSO-induced toxicities in urinary bladder. The restoration of GSH through the treatment with the hydroxytyrosol extract can play an important role in reversing CP-induced apoptosis and free radical-mediated LPO.

Short- and Long-Term Outcomes of Living Donors in Tunisia: A Retrospective Study

Despite initiatives to increase cadaveric donation, there is still a shortfall in donor organs. Kidneys from living donors now makes a significant contribution to increasing the number of organs available for transplantation in Tunisia. We performed a retrospective study of 405 kidney transplantations, including 321 (79.3%) from living donors performed from June 1986 to December 2007. We obtained information on only 162 (50.4%), namely, 64 men (39.5%) and 98 women (60.5%), whose mean age at the time of donation was 42.3 ± 12.2 years. Twelve (8.22%) perioperative complications occurred: wound infections (n = 4), pneumothorax (n = 4), phlebitis (n = 1), hematomas (n = 2), and urinary infection (n = 1). The mean follow-up period was 117.4 ± 74.4 months. Hypertension occurred in 42 donors (25.9%) with mean values of 134 ± 20 for systolic and 79 ± 10 for diastolic blood pressure. Twelve donors (7.4%) developed proteinuria (mean proteinuria, 0.08 ± 1.25 g/d). Renal insufficiency was found in 28 donors (19.44%), 2 of whom developed chronic renal failure requiring dialysis at intervals of 36 and 84 months. In both cases, we diagnosed a familial form of focal segmental glomerulosclerosis. Two donors (1.2%) died within 10 years after kidney donation due to senility. The relatively favorable outcomes suggest that living-donor kidney transplantation is an acceptable approach, in view of the superior results it yields in recipients. However, efforts to increase the number of cadaveric donors in Tunisia should be made. It is also important to develop a registry of long-term kidney function after kidney donation.

Prognostic Value of Serum C-Reactive Protein in Spontaneous Intracerebral Hemorrhage: When Should We Take the Sample?

BACKGROUND Several studies showed a correlation between C-reactive protein and mortality in spontaneous intracerebral hemorrhage. However, the best time to measure C-reactive protein to assess prognosis is not yet clear. The purpose of this study was to determine if initial or H24-C-reactive protein is independently associated with 30-day mortality in intracerebral hemorrhage. METHODS This is a retrospective study done within years 2010-2015. All intracerebral hemorrhage cases with missing data or with autoimmune disease or neoplasm were excluded. Univariate and multivariate analyses were assessed for initial C-reactive protein, H24-C-reactive protein, and confounding factors. RESULTS Of 122 patients, 91 were selected. Only H24-C-reactive protein, hematoma volume, and infratentorial origin were independently associated with 30-day mortality in intracerebral hemorrhage. When adjusted with intracerebral hemorrhage score, H24-C-reactive protein with a cutoff value of 30 mg/L independently predicted 30-day mortality. CONCLUSIONS This study suggests that H24-C-reactive protein may be a more reliable marker than initial C-reactive protein in the prediction of mortality in intracerebral hemorrhage. A large multicentric study is necessary to confirm the interest of including H24-C-reactive protein to a modified intracerebral hemorrhage score for the prediction of 30-day mortality.

Hemorrhagic Shock as Complication of Intramural Intestinal Bleeding

Introduction. Mural intestinal hematoma (MIH) is an uncommon complication of anticoagulant therapy. Hemorrhagic shock has been rarely reported as a revealing modality. Results. We report two cases of shock induced by mural intestinal hematoma in patients under oral anticoagulant for aortic prosthetic valve and atrial fibrillation. Patients were admitted to the ICU for gastrointestinal tract bleeding associated with hemodynamic instability. After resuscitation, an abdominal CT scan has confirmed the diagnosis showing an extensive hematoma. Medical treatment was sufficient and there was no need for surgery. Conclusion. Gastrointestinal bleeding associated with shock in patients treated by oral anticoagulant should alert physicians to research a probable MIH. Urgent diagnosis and appropriate medical treatment can avoid surgical interventions.

Vasitis: An Uncommon Diagnosis Mimicking Incarcerated Inguinal Hernia

Vasitis or inflammation of the vas deferens is a rarely described condition. Clinically, it presents with nonspecific symptoms that can be confused with other more common conditions, especially an incarcerated inguinal hernia. The diagnosis may be suggested by ultrasound or, more precisely, by computed tomography.

Le lymphangiome kystique rétropéritonéal: à propos de 5 cas et revue de la littérature

Cystic lymphangioma is a rare, benign malformation of the lymphatic vessels which may be observed on various locations. Retroperitoneal location is less common than mesenteric location. Cystic lymphangioma has a polymorphic clinical presentation. Diagnosis is based on imaging but requires histological confirmation. Surgery is the treatment of choice. The aim of our study is to analyze the clinical manifestations, complications, diagnostic and therapeutic aspects of this tumor. We report a case series of 5 patients with retroperitoneal cystic lymphangioma (4 women and 1 man) operated in our department between the years 2004 and 2014. Their medical records were reviewed retrospectively. Follow-up was based on clinical examination and abdominal CT scan. The average age was 45 years. The mean follow-up was 32.6 months. The most common symptoms indicative of retroperitoneal cystic lymphangioma were pains and/or an abdominal mass. Abdominal CT scan was the most useful diagnostic test. Total resection was immediately achieved in 4 patients and it was deferred for up to 5 years in one patient. He underwent annual ultrasound monitoring. One patient underwent nephrectomy. No recurrence or complications were noted in 5 patients. Retroperitoneal cystic lymphangioma is a rare condition. Its therapeutic management is based on complete resection in patients with symptomatic lesions or complications, in order to limit the risk of recurrence. Complete resection may be deferred in asymptomatic patients.

Discovery of Renal Tuberculosis in a Partial Nephrectomy Specimen Done for Renal Tumor.

The association of renal cancer and renal tuberculosis is uncommon. While the incidental discovery of renal cell carcinoma in a tuberculous kidney is a classical finding, the discovery of tuberculous lesions after nephrectomy for cancer is exceptional. We report the case of a female patient aged 60 who had a partial nephrectomy for a 5 cm exophytic kidney tumor. Pathological examination concluded that renal clear cell carcinoma associated with follicular caseo tuberculosis.