Mohamed Riadh Ben Slama

Hydatid Cyst of the Kidney: Diagnosis and Treatment

Renal echinococcosis is relatively uncommon compared to liver and lung localizations. Kidney involvement represents 4% of confirmed cases of hydatid disease. We reviewed the clinical findings of a personal series of renal hydatidosis with emphasis on diagnostic and therapeutic issues. A total of 178 renal cysts were collected over a period of 33 years from 1963 to 1996. Clinical, radiologic and laboratory data are analyzed. Radiologic exploration has had an interesting evolution, with the appearance of ultrasonography and computed tomography. Diagnostic accuracy has been greater since the availability of ultrasonography and immunologic studies. Their contribution to the diagnosis of renal hydatid disease is important. We try, with our experience of ultrasonography in the matter of renal hydatid cysts, to underline the role of this exploration. The treatment of hydatid cyst of the kidney is surgical. Renal-sparing surgery, cystectomy plus pericystectomy, is possible in most cases (75%). Nephrectomy (25% of cases) must be reserved for destroyed kidneys resulting from aged cysts opening into the excretory cavities and complicated by renal infection. Whether conservative or radical, the first surgery performed is cystectomy, with germinate membrane removal after controlled evacuation and opening of the cyst, making the subsequent steps of surgery easier. A renal hydatid cyst is a benign parasitic infestation caused by larval growth of the cestode Echinococcus granulosus. Hydatid disease, despite preventive measures, continues to be endemic in sheep-raising countries of the Mediterranean area, Africa, and Latin America, but it may occur in other regions owing to increased travel and migration. The renal hydatid cyst is uncommon compared to that in the liver or lung. Kidney involvement [1] represents 4% of all cases. The various anatomic localizations, based on a series of 1713 cases, collected during 10 years at Charles Nicolle Hospital in Tunis are noted in Table 1. This distribution is explained by the parasitic cycle; most of the parasites are trapped by hepatic and pulmonary filters. The incidence of hydatid disease officially diagnosed is 15 per 100,000 [2]. A homogeneous series of 178 patients with renal hydatidosis are studied with particular emphasis on diagnosis and therapeutic issues. Materials and Methods A retrospective 33-year review of 178 renal hydatid cysts, surgically treated and confirmed by pathology, is analyzed. The first 48 cases were treated at Algiers (Algeria) from 1963 to 1973 and the last 130 cases at Tunis from 1974 to 1996. Clinical symptoms at presentation, imaging modalities, serologic findings, type of surgery, and results were recorded for each case. Imaging modalities changed according to the year of the diagnosis. Intravenous pyelography (IVP), sometimes retrograde pyelography, and arteriography were used during the 1960s and 1970s. Ultrasonography (US) and sometimes computed tomography (CT) were used later. Laboratory tests included Casoni’s skin test during the initial years, but this was later replaced by serologic explorations.

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).

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.

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.

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.

Combined Analysis of Smoking, TP53, and FGFR3 Mutations in Tunisian Patients with Invasive and Superficial High-Grade Bladder Tumors

ABSTRACT In our cohort,FGFR3 mutations were detected in 31.1% of bladder tumors and are associated with lower stage and grade. Concerning TP53, 62 mutations were found in tumors from 44 cases (48.88%) and are associated with advanced forms. The combined analysis of FGFR3 and TP53 mutations in our cohort showed an independent distribution. In addition, we have reported that FGFR3 mutations spectrum depends on the intensity of tobacco use (pack years: PY). Finally, we have found that the FGFR3wt/TP53mut genotype, which was associated with advanced bladder tumors; was overrepresented in light smokers (PY < 40) compared to nonsmoker patients (p =.01).

Endoscopic Bridge Operating-Guide Device Applied for Intracorporeal Antegrade Ureteric Stenting During Laparoscopic Pyeloplasty

AIM To describe our novel technique of laparoscopic pyeloplasty with an antegrade placement of a ureteral stent with a bridge operating-guide device (BOGD). METHODS After completing the posterior suture line of the dismembered pyeloplasty, a guidewire is inserted through the BOGD and grasped within the renal pelvis. Then, the BOGD is removed and the ureteral stent advanced until it is positioned in the renal pelvis, and the lower end of the stent lies in the bladder. The anastomosis is completed. Fifteen patients underwent the laparoscopic placement of ureteral stents with this technique. RESULTS With this method, the ureteral stent insertion is very convenient and time saving (the mean time for inserting a stent was 5 minutes). The stents were successfully inserted in all patients. CONCLUSIONS This technique is reliable and effective in laparoscopic ureteral operations. It uses an endoscopic urological equipment, and costs are reduced.

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).

Voluminous Incidental Oncocytic Neoplasm of the Adrenal Gland With Uncertain Malignant Potential

A 74-year-old man presented with right flank pain and a palpable mass in the left flank. Blood pressure was normal. Contrastenhanced computed tomography (CT) showed a 17 × 16 × 12 cm retroperitoneal mass over the left kidney, solid and heterogeneous. There were also 3 retro aortic lymph nodes and bilateral renal lithiasis. Twenty four-hour urinary metanephrines and normetanephrines were normal. The patient underwent a resection of the mass with left adrenalectomy by a lumbar incision. Histological findings revealed an adrenal oncocytic neoplasm (AON) with uncertain malignant potential. Six months after surgery, CT control showed neither local nor distant recurrence.

The impact of smoking and polymorphic enzymes of xenobiotic metabolism on the stage of bladder tumors: a generalized ordered logistic regression analysis.

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 N-acetyltransferases (NAT) and glutathione S-transferases (GST). Polymorphisms in NAT and GST genes alter the ability of these enzymes to metabolize carcinogens. In this paper, we conduct a statistical analysis based on logistic regressions to assess the impact of smoking and metabolizing enzyme genotypes on the risk to develop bladder cancer using a case–control study from Tunisia. We also use the generalized ordered logistic model to investigate whether these factors do have an impact on the progression of bladder tumors.