Polymorphisms in one-carbon metabolism pathway genes and risk for bladder cancer in a Tunisian population.

Cigarette smoking is the most important risk factor for bladder cancer. Moreover, epidemiologic studies have implicated several genetic variations interfering with methyl group metabolisms in susceptibility for a variety of cancers. Examples of these variations can be found in genes of the folate metabolic pathway, which is crucial in the provision of methyl groups for DNA, RNA, and protein methylation, as well as in purine and pyrimidine synthesis. We conducted a case-control study to examine the relationship between the methylenetetrahydrofolate reductase (MTHFR C677 T and MTHFR A1298C), methionine synthase (5-methyltetrahydrofolate-homocysteine methyltransferase, MTR A2756 G), methionine synthase reductase (5-methyltetrahydrofolate-homocysteine methyltransferase reductase, MTRR A66 G and MTRR C524 T), and thymidylate synthase (TYMS 2R-->3R and G/C) genotypes and the risk for bladder cancer in a Tunisian population. The isolated MTHFR 677 *T, MTRR 66 *G and MTRR 524 *T variants did not appear to influence bladder cancer susceptibility. The 3R *C/3R *C genotype for the TYMS gene appears to be a protective factor against bladder cancer development (P=0.0001; OR=0.12; 95% CI=0.03-0.40). However, patients heterozygous for MTHFR A1298C or MTR A2756 G genotypes have 1.62- and 2.13-fold higher risk, respectively, of developing bladder cancer. Moreover, the combined study of MTHFR 1298 *C and MTR 2756 *G variants with either or both MTRR 66GG and TYMS 3R *G/3R *G genotypes suggests a cumulative effect. Finally, this study evidenced that interaction between gene variations involved in folate metabolism and risk of bladder cancer increased dramatically among smokers.

Combined effect of smoking and inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 on bladder cancer in a Tunisian population.

Cigarette smoking is the predominant risk factor for bladder cancer in males and females. The tobacco carcinogens are metabolized by various xenobiotic metabolizing enzymes, such as the super-families of N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. We have conducted this case-control study to assess the role of smoking, slow NAT2 variants, and GSTM1 and GSTT1 null genotypes in bladder cancer development in North Tunisia. In all groups of patients, we have shown that GSTM1 and GSTT1 null genotypes did not appear to be a factor affecting bladder cancer susceptibility. For the NAT2 slow acetylator genotype, the NAT2*5/*7 diplotype was found to have a 7-fold increased risk of bladder (OR=7.14; 95% CI: 1.30-51.41). Furthermore, we found that NAT2 slow acetylator individuals temporarily carrying wild-type GSTT1 or GSTM1 null genotypes have a strong increased risk of bladder cancer (OR= 26 and 22.17, respectively). This cumulative effect was estimated at 12 for smokers harboring slow or an intermediate NAT2, GSTM1 null, and wild-type GSTT1 genotypes compared to non-smokers carrying rapid NAT2, wild-type GSTM,1 and GSTT1 null genotypes (p=0.02; OR=12; CI 95% 1-323.76).

The role of CYP2D6*4 variant in bladder cancer susceptibility in Tunisian patients.

CYP2D6 enzyme is implicated in the metabolism of drugs and nicotine. Genetic variability within CYP2D6, results in different CYP2D6 phenotypes. Inheritance of polymorphic CYP2D6 metabolizing enzyme is likely to be an important determinant of inter-individual variations in susceptibility to cancer. In this work, we have conducted a case control study in order to assess the role of CYP2D6*4 variant in bladder cancer development in a Tunisian cohort. A total of 80 patients with TCC of bladder cancer and 109 healthy controls were included in the present study. The frequency of CYP2D6*4 allele, characterized by loss of BstNI site, was observed in 8.25% of healthy volunteers and in 10.62% of patients. The CYP2D6*4/CYP2D6*4 genotype was observed in only 2.75% of controls and was absent in cases. In all group of patients, the CYP2D6*4 allele did not appear to influence bladder cancer susceptibility (p > 0.05). A similar result was obtained when we stratified cases group according to tobacco status. Conversely, patients carrying the BstNI site at the homozygous state, mostly combined as homozygous wild genotype, could be at more risk of bladder cancer invasiveness than those having the heterozygous genotype.

Fracture of the penis: management and long-term results of surgical treatment. Experience in 300 cases.

BACKGROUND: Herein, we present the largest series of penile fracture ever published. We evaluate the clinical presentation, the outcome of the treatment and the prognosis. METHODS: We retrospectively studied patients with penile fracture treated from 1975 to 2005. RESULTS: Three hundred patients were included in this study. The mean patient age was 30 years (range, 18-68 years). Out of these patients, 57 (19%) patients were injured during sexual intercourse, whereas 180 (60%) patients were injured during masturbation. The mean time from injury to presentation was 26 hours. The diagnosis was clinical in all cases. No further investigation was needed for confirming the diagnosis. Five patients had urethral bleeding with urethral lesion. All patients were treated by immediate surgery. All of the patients had a tunica albuginea tear that was promptly repaired. At follow-up (mean time of 7 years), 14 patients presented mild curvature, which had not hindered intercourse in 10 patients. The Nesbit intervention was performed in four patients. Penile pain at intercourse developed in four patients (1.3%) and at erection in six patients (2%). Erectile dysfunction was observed in two cases (0.6%). CONCLUSION: Penile fracture has typical clinical signs. Early surgical treatment is associated with a low incidence of late complications. The high frequency in our area is neither because of physical nor genetic particularities. It is probably because of sociocultural characteristics.

[US guided biopsy in the early diagnosis of prostatic cancer. A series of 66 cases]. / Biopsie échoguidée dans le diagnostic précoce du cancer de la prostate. A propos de 66 cas.

AIM: Our study's aim is to evaluate the reliability of digital rectal examination and serum PSA in the indication of prostatic biopsy. METHODS: 66 patients with abnormal digital rectal examination and arised PSA levels had prostatic biopsies. The sextant technique was practiced. RESULTS: The digital rectal examination had a sensitivity of 65%, a specificity of 45% and a positive predictive value (PPV) of 34.3%. The serum PSA had a PPV of 25%. The association if these two parameters arised the PPV to 39.5%. Cancer detection rate was estimated to 30.3%. CONCLUSIONS: Prostatic biopsies should be indicated according to the result of digital rectal examination and serum PSA.

[Retroperitoneal leiomyosarcoma: report of 3 cases]. / Les leiomyosarcomes retroperitoneaux: à propos de 3 cas.

BACKGROUND: Retroperitoneal leiomyosarcomas are neoplasma which are best treated with complete exeresis. AIM: We reported three new cases of retroperitoneal Leiomyosarcoma operated during last ten years. CASES: The authors reported 3 cases of Retroperitoneal leiomyosarcomas in 3 patients (2 men and a woman) aged respectively 53, 55 and 57 year-old. Incomplete resection was performed in the 3 cases because of the important local extension. All patients died 18, 19 et 51 months after diagnosis.

[Prognostic value of the immunohistochemical expression of: Ki67, p53, PCNA and Bcl2 in the superficial tumors of the bladder]. / Valeur pronostique de l'expression immunohistochimique de: Ki67, p53, PCNA et Bcl2 dans les tumeurs superficielles de la vessie.

AIM: To study a serie of superficial tumors of the bladder and to assess the prognostic significance of p53, Ki67, PCNA and bcl2 in these tumors. METHODS: We studied 59 bladder tumors: 43 pTa and 16 pT1. All Patients had cystoscopy 3 months after the resection and tumors that did not recur had a minimum follow up of 5 years. RESULTS: Age more than 65 years (p = 0,001), multifocality (p=0,022) and tumoral size > or = 3 cm (p = 0,022) were correlated with the recurrence. The expression of p53 was correlated with the recurrence in the year following the tumoral resection (p = 0,035). That of of Ki67 was correlated with the histological grade (p = 0,03) and stage (p=0,002). CONCLUSION: Our results suggest to practise regular endoscopic controls during the first year following the resection of the primitive tumor if it expresses p53. The immunohistochemical expression of Ki67 being correlated with the grade, this marker could help to better classify the tumors of intermediate grade.

Methylenetetrahydrofolate reductase and methionine synthase polymorphisms and risk of bladder cancer in a Tunisian population.

Folate insufficiency can induce carcinogenesis by decreasing DNA methylation. It is well known that DNA hypomethylation is a common feature in a number of cancers. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are enzymes that play central roles in the folate metabolic pathway. Two common polymorphisms in the MTHFR gene (C677T and A1298C) and one in the MS gene (A2756G) are associated with decreased enzymatic activity. In this work, we have conducted a case-control study to assess the role of these three polymorphisms in bladder cancer development in North Tunisia. For MS A2756G, gene and genotypic distributions differed significantly between cases and controls. Furthermore, individuals carrying at least one copy of the variant allele presented a 2.33 times increased risk of developing bladder cancer than their control group [P = 0.001, odds ratio (OR) = 2.33; 95% confidence interval (CI) 1.34-4.06]. Statistically significant odds ratios were also found in patients heterozygous for MTHFR A1298C, who have a 1.8-fold higher risk of developing bladder cancer (P = 0.03, OR = 1.86; CI 95% 1.04-3.33). While the isolated polymorphism C677T did not appear to influence bladder cancer susceptibility, results suggest that it might act with an additive contribution determined by variation at MTHFR A1298C. Identical cumulative effect was detected for the MTHFR A1298C and MS 2756 genotypes. Patients harboring at least one mutant allele for each of the three positions analyzed showed a 4.76-fold increased risk of developing bladder cancer in comparison to their reference group (P = 0.02, OR = 4.76; CI 95% 1.26-17.98).

[Retroperitoneal ganglioneuroma. A case report]. / Le ganglioneurome rétropétritonéal. A propos d'un cas.

BACKGROUND: Ganlioneuroma is a rare, benign, neurogenic tumor originating from the neural sheath and frequently localized in the retroperitoneum. AIM: Report of a new case. CASE: We report a case of a 36-year-old woman presenting isolated right lumbar pain. Computed tomography revealed a heterogeneous, right, retroperitoneal mass, 13 cm in diameter. Complete resection of the tumor and right nephrectomy were performed. Histology confirmed the diagnosis of ganglioneuroma. Follow-up was 10 months with no recurrence. Through this case, we discuss diagnostic, therapeutic and prognostic aspects of this disease.

[Surgical treatment of post-traumatic complete urethral rupture: deferred urgent urethral suture or delayed repair?]. / Le traitement chirurgical des ruptures urétrales complètes post-traumatiques : l'urétrorraphie en urgence différée ou la réparation retardée?

OBJECTIVE: To compare the results of deferred urgent surgical treatment and delayed repair in post-traumatic complete urethral rupture. PATIENTS AND METHOD: Between 1986 and 2003, sixty patients were operated for complete rupture of the posterior urethra. In the absence of any serious visceral or skeletal lesions, 32 patients were operated within five to ten days (Group I). In 28 cases (Group II), patients were operated 8 months after the injury via a perineo-transsymphyseal approach. RESULTS: The mean age of these patients was 28 years (range: 18 to 53 years). With a minimum follow-up of 2 years (range: 2-14 years), the urine stream was considered to be satisfactory in 90% of patients of group I and in 100% of cases of group II. Continence was perfect in 91% of patients in the two groups. Erectile dysfunction was observed in 22% of cases of Group I versus 28.5% of cases of Group II. CONCLUSION: Deferred urgent end-to-end urethral suture and delayed urethroplasty give globally comparable results. Deferred urgent end-to-end urethral suture must be performed whenever possible. The perineo-transsymphyseal approach must be reserved to the treatment of large stenoses in multi-operated or delayed repair patients.

[Post traumatic rupture in patients with uretero pelvic junction obstruction. Case report]. / Rupture post - traumatique d'un syndrome de la jonction pyelo -ureterale meconnu. A propos d'une observation.

Authors report a case of post traumatic pelvic rupture occurring in an unknown ureteropelvic junction (UPJ) obstruction. Ultrasonography showed pyelectasia and fluid effusion in the anterior perirenal space. CT scan confirmed the diagnosis of UPJ obstruction and showed the rupture of the anterior pelvic wall communicating with a perirenal urinoma. The patient underwent a retrograde stenting for decompression and surgical drainage of the urinoma. Pyeloplasty was performed 4 months after injury. A follow up intravenous pyelogram showed good flow through the repair and the patient remaines asymptomatic 2 years after treatment. Post traumatic rupture of UPJ obstruction is a rare event with few reported cases in literature. Diagnosis is suggested on imaging studies. CT scan shows the rupture site in the ureteropelvic tract and guides percutaneous drainage.

[Inverted papilloma of the bladder: diagnosis and course]. / Le papillome inversé de la vessie: diagnostic et evolution.

OBJECTIVE: To analyse the diagnosis, treatment and clinical course of inverted papilloma of the bladder MATERIALS AND METHODS: Between January 1980 and January 2004, 12 patients with an inverted papilloma of the bladder were included, representing 0.36% of all bladder tumours treated over the same period. RESULTS: This series consisted of 10 men and 2 women with a mean age of 62 years (range: 42-83 years). The most frequent presenting complaint was macroscopic haematuria (10/12 cases), associated with signs of bladder irritation in 8 cases. This lesion was solitary and frequently located in the trigone (7/12 cases). An associated transitional cell carcinoma was diagnosed in 5 cases. CONCLUSION: Inverted papillomas of the bladder are rare, benign tumours that can be associated with urothelial carcinoma, requiring rigorous surveillance.

Prognostic factors of recurrence after vesicovaginal fistula repair.

PURPOSE: We evaluate the prognostic factors of recurrence in patients after the surgical repair of vesicovaginal fistula. MATERIALS AND METHODS: From 1985 to 2002, 73 women with vesicovaginal fistula underwent late (> 3 months) surgical repair. A multivariate analysis of the data was performed with the EPI-INFO software. All P-values were two-sided, with odds ratio and 95% confidence intervals. RESULTS: A total number of 73 patients underwent 97 procedures with a mean rate of 1.38 procedures/patient. The overall surgical success rate was 86.7%. Multivariate analysis demonstrated that recurrence was statistically significant for multiple fistulas (single vs two or more), fistula size (>10 mm), fistula type (Type I vs Type II), fistula etiology (obstetrical vs non-obstetrical) and the presence of urinary tract infection before the repair. Recurrence risk was fivefold higher for both the size and the type of the fistula, threefold higher for obstetrical etiology and 4.5-fold higher for multiple fistula. The interposition of flaps was a protective factor for recurrent cases. The surgical approach was not a significant prognostic factor of recurrence. CONCLUSION: Successful closure of a vesicovaginal fistula requires an accurate and a timely repair using procedures that exploit basic surgical principles. Multiple fistula, size and type of the fistula, and obstetrical etiology were the recurrence risk factors. We recommend in all patients with multiple risk factors for recurrence, the interposition of flaps.

The role of glutathione transferases M1 and T1 in individual susceptibility to bladder cancer in a Tunisian population.

BACKGROUND: Susceptibility to bladder cancer is thought to depend on interplay between genetic factors and environmental chemical carcinogens. AIM: This study seeks to determine the role of the glutathione transferases M1 and T1 null genotypes (GSTM1*0 and GSTT1*0) in individual susceptibility to bladder cancer in a Tunisian population. METHOD: Sixty-two patients with transitional cell carcinoma of the bladder cancer and 79 controls were examined with respect to the frequency of GSTM1 and GSTT1 null genotypes. RESULTS: The frequencies of the GSTT1 null in the total group of bladder cancer cases vs. controls did not differ statistically. The proportion of GSTM1 null genotype in patients was 63% compared to 45% in controls group (OR = 2.03; 95% CI 0.97-4.24; p = 0.04). A significantly higher incidence of GSTM1 deletion genotype was found in smokers with bladder cancer compared to the controls (65.38% vs. 45.5%). Smokers lacking the GSTM1 gene are at an approximately 2.2-fold higher risk of bladder cancer (OR= 2.23, 95% CI 1-5.15; p = 0.03). CONCLUSION: This study suggests that in Tunisian subjects the GSTM1 null genotype may be associated with an increased risk of bladder cancer. This association appears to depend upon smoking status.

[Renal adenocarcinoma in horseshoe kidney, report of a case]. / L'adénocarcinome rénal sur rein en fer à cheval. A propos d'un cas.

Tumors arising within horseshoe kidney are uncommon and may be difficult to identify. The incidence of tumor within horseshoe kidney is higher than in the normal one. Adenocarcinoma is the most common tumor. The nephrectomy is considered as partial and the patients need a strict follow up. Horseshoe kidneys show a lot of variety with regard to supporting arteries and veins. Therefore, a selective study of the renal vessels should be performed preoperatively. Abdominal angiography should be done to study this vasculature.

[Emphysematous pyelonephritis. Two cases]. / La pyélonéphrite emphysémateuse. A propos de deux observations.

The emphysematous pyelonephritis is a rare and severe renal infection characterized by the presence of gas in renal parenchyma and its perirenal spaces. We report two cases of emphysematous pyelonephritis in two diabetic women (53 and 50 years old respectively). In the first case, the treatment was based on nephrectomy because of the presence of a septic shock and three risk factors, which are acute renal failure, hematuria and thrombopenia. In the second case, the treatment was only medical. The evolution was favorable in the two cases. We insist in this article that this diagnosis should be considered in every female diabetic patient having severe acute pyelonephritis resistant to a well-conducted medical treatment.

[Ureterocalicostomy: last resort in the treatment of certain forms of ureteropelvic junction stenosis. Report of 5 cases]. / L'urétérocalicostomie: ultime recours dans le traitement de certaines sténoses de la jonction pyélourétérale (a propos de 5 cas).

INTRODUCTION: Iatrogenic stenoses of the ureteropelvic junction are now essentially treated by endoscopic techniques. However, conventional surgery is sometimes required to treat severe or extensive stenosis. The authors report the use of ureterocalicostomy to treat 5 patients with complex lesions. MATERIAL AND METHODS: Between 2001 and 2003, the authors treated five patients with iatrogenic stenosis of the ureteropelvic junction. Two of these patients had a history of percutaneous nephrolithotomy and the other three had undergone conventional pyelotomy, complicated by pyelocaliceal avulsion in one case. The diagnosis was confirmed by double anterograde and retrograde opacification in four patients and intravenous urography in one patient. It was decided to perform ureterocalicostomy due to the extent of the lesions. Inferior ureterocalicostomy was performed after lower pole nephrectomy in all cases. RESULTS: The mean follow-up was 21 months (range: 20 to 27 months). Three patients had an uneventful postoperative course and satisfactory radiological follow-up. One patient rapidly developed stenosis that was treated successfully by endoscopy and another patient obtained a poor result requiring nephrectomy. CONCLUSION: Ureterocalicostomy requires laborious surgical dissection and meticulous ureterocaliceal anastomosis, but it is a useful technique in some cases of severe and extensive iatrogenic stenosis of the ureteropelvic junction.