Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer and subsequent cluster selection of the patient population undergoing standard radical prostatectomy.

AIM: A preceding exploratory analysis has shown that follicle-stimulating hormone (FSH) was significantly correlated to and predicted by prostate-specific antigen (PSA) in a prostate cancer population. The aim of the study was to evaluate FSH physiopathology along the pituitary-testicular-prostate (PTP) axis at the time of initial diagnosis of prostate cancer in an operated population clustered according to the FSH/PSA ratio. PATIENTS AND METHODS: The study included 93 patients who underwent standard radical prostatectomy. Age, percentages of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), luteinizing hormone (LH), FSH, prolactin hormone (PRL), total testosterone (TT), free testosterone (FT), estradiol (ESR) and PSA were the continuous variables. Category variables were pT and biopsy/pathology Gleason pattern I/II (b/pGPI/II). The population was clustered according to the FSH/PSA ratio which was computed from empirical data and then ranked for clustering the population as groups A (range 0.13 ≤ FSH/PSA ≤ 0.20), B (range 0.20 < FSH/PSA ≤ 0.50), C (range 0.50 < FSH/PSA ≤ 0.75), D (range 0.75 < FSH/PSA ≤ 1.00), E (range 1.00 < FSH/PSA ≤ 1.25), F (range 1.25 < FSH/PSA ≤ 2.00), G (range 2.00 < FSH/PSA ≤ 2.25), H (range 2.25 < FSH/PSA ≤ 6.40) and I (range 6.40 < FSH/ PSA ≤ 19.40). The model was assessed by simple linear regression analysis and differences between the groups were investigated by analysis of variance (ANOVA) for continuous variables and by contingency tables for category variables. RESULTS: FSH was significantly correlated to and predicted by PSA in groups A (p = 0.04), B (p < 0.0001), C (p < 0.0001), D (p < 0.0001), E (p < 0.0001), F (p < 0.0001), G (p < 0.0001), H (p = 0.0001) and I (p = 0.001). Also, clusters (A-I) differed significantly for mean values of FSH (p < 0.0001), LH (p < 0.0001), TT (p = 0.04), PSA (p < 0.0001), bGS (p = 0.005), pGS (p = 0.01) and PSA/FT ratio (p < 0.0001); moreover, the nine groups showed significant different frequency distributions of pGPI (p = 0.02), pGPII (p = 0.0002) and bGPI (p = 0.04). CONCLUSION: The ranking FSH/PSA ratio significantly clustered, along the PTP axis, an operated population diagnosed with prostate cancer. Also, the ranking FSH/PSA ratio selected prostate cancer clusters expressing different levels of hormonal disorder along the PTP axis and prognostic potential with different risks of progression. As a theory, in the current advancing world, the ranking FSH/PSA model might be considered as an interesting and effective tool for prostate cancer study as well as individualized, risk-adapted approaches of the disease. However, confirmatory studies are needed.

Investigative clinical study on prostate cancer part VIII: prolactin hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population after radical prostatectomy.

AIM: To evaluate the prolactin hormone (PRL) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer and the subsequent cluster selection of the patient population after radical prostatectomy in relation to clinical and pathological variables. PATIENTS AND METHODS: Ninety-two operated prostate cancer patients were retrospectively reviewed. No patient had previously received hormonal treatment. The investigated variables included PRL, follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), total prostate specific antigen (PSA), percentage of positive cores at transrectal ultrasound scan biopsy (TRUSB) (P+), biopsy Gleason score (bGS), pathology Gleason score (pGS), estimated tumor volume in relation to percentage of prostate volume (V+), overall prostate weight (Wi) and age. Empirical PRL correlations and multiple linear predictions were investigated along the pituitary testis prostate axis in the different groups of the prostate cancer population and clustered according to pT (2a/b, 3a, 3b/4) status. The patient population was classified according to the log(10) PRL/V+ ratio and clustered as follows: group A (log(10) PRL/V+ ≤1.5), B (1.5< log(10)PRL/V+ ≤2.0) and C (log(10) PRL/V+ >2.0). Simple linear regression analysis of V+ predicting PRL was computed for assessing the clustered model and analysis of variance was performed for assessing significant differences between the groups. RESULTS: PRL was independently predicted by FSH (p=0.01), LH (p=0.008) and P+ (p=0.06) in low-stage prostate cancer (pT2a/b). Interestingly, PRL was independently predicted by LH (p=0.03) and FSH, TT, FT, PSA, bGS, pGS, V+, Wi and age (all at p=0.01) in advanced stage-disease (pT3b/4). V+ was also significantly correlated (r=0.47) and predicted by P+ (p<0.0001) in the prostate cancer population. PRL was significantly correlated and predicted by V+ when the patient population was clustered according to the log(10)PRL/V+ ratio in group A (p=0.008), B (p<0.0001) and C (p<0.0001). Moreover, the three groups had significantly different mean values of PRL (p<0.0001), PSA (p=0.007), P+ (p=0.0001), V+ (p<0.0001), Wi (p=0.03), bGS (p=0.008), pGS (p=0.003); also, groups A, B and C had significant different pGS (p=0.03), pT (p=0.0008) and pR (p=0.01) frequency distributions. CONCLUSION: At diagnosis, in an operated prostate cancer population, PRL was significantly correlated and independently predicted along the pituitary testis prostate axis in high-stage disease; V+ was also significantly correlated and predicted by P+. Because of the high correlation and prediction of PRL by both V+ and P+, the prostate cancer population at diagnosis was clustered according to the log(10)PRL/V+ ratio into groups A, B and C that, in theory, might be models with prognostic potential and clinical applications in the prostate cancer population. However, confirmatory studies are needed.

Investigative clinical study on prostate cancer part VI: Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

AIM: To evaluate the physiopathology of follicle-stimulating hormone (FSH) along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. PATIENTS AND METHODS: The study included 98 patients who were diagnosed with prostate cancer. Age, percentages of positive cores (P+) at transrectal ultrasound scan biopsy, biopsy Gleason score (bGS), luteinizing hormone (LH), FSH, total testosterone, free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had not previously received hormonal manipulations. FSH correlation and multiple linear analyses were computed in the population. The FSH/PSA ratio was computed and then ranked for clustering the population as groups A (0.13≤FSH/PSA≤0.57), B (0.57

Investigative clinical study on prostate cancer part VII: prolactin and the pituitary-testis-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

AIM: To evaluate prolactin (PRL) physiopathology along the pituitary-testis-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. PATIENTS AND METHODS: The study involved 100 individuals diagnosed with prostate cancer. Age, percentage of positive cores at transrectal ultrasound scan biopsy (P+), biopsy Gleason score (BGS), PRL, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had histologically proven carcinoma of the prostate and had not previously received hormonal manipulations. Correlation and multiple linear regression analysis of the the variables along the pituitary-testis-prostate cancer axis was performed. The prostate cancer population was clustered according to the PRL/P+ ratio into group A (4.20≤PRL/P+ ≤20), B (20

Investigative clinical study on prostate cancer part IV: exploring functional relationships of total testosterone predicting free testosterone and total prostate-specific antigen in operated prostate cancer patients.

OBJECTIVES: To explore, in operated prostate cancer patients, functional relationships of total testosterone (tt) predicting free testosterone (ft) and total PSA. PATIENTS AND METHODS: 128 operated prostate cancer patients were simultaneously investigated for tt, ft and PSA before surgery. Patients were not receiving 5α-reductase inhibitors, LH-releasing hormone analogues and testosterone replacement treatment. Scatter plots including ft and PSA versus tt were computed in order to assess the functional relationship of the variables. Linear regression analysis of tt predicting ft and PSA was computed. RESULTS: tt was a significant predictor of the response variable (ft) and different subsets of the patient population were assessed according to the ft to tt ratio. PSA was related to tt according to a nonlinear law. tt was a significant predictor of PSA according to an inversely nonlinear law and different significant clusters of the patient population were assessed according to the different constant of proportionality computed from experimental data. CONCLUSIONS: In our prostate cancer population, ft was significantly predicted by tt according to a linear law, and the ft/tt ratio was a significant parameter for assessing the different clusters. Also, tt was a significant variable predicting PSA by a nonlinear law and different clusters of the patient population were assessed by the different constants of proportionality. As a theory, we explain the nonlinear relation of tt in predicting PSA as follows: (a) the number of androgen-independent prostate cancer cells increases as tumor volume and PSA serum levels rise, (b) the prevalence of androgen-independent cells producing a substance which inhibits serum LH, and (c) as a result lower levels of serum tt are detected.

Investigative clinical study on prostate cancer Part V: Luteinizing hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

AIM: To evaluate Luteinizing hormone (LH) physiopathology along the pituitary testicular prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. PATIENTS AND METHODS: Age, percentages of positive cores at Trans Rectal Ultrasound Scan Biopsy (TRUSB) (P+), biopsy Gleason score (bGS), LH, Total Testosterone (TT), Free Testosterone (FT) and Prostate Specific Antigen (PSA) were the continuous clinical variables. All patients had histologically proven carcinoma of the prostate and had not previously received 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement treatment. Correlation analysis was performed for the patient population. Correlation analysis, linear regression and analysis of variance was computed in groups and subgroups of the prostate cancer population. RESULTS: Correlation analysis of the patient population showed that LH was significantly correlated to age (p=0.02) and FT (p=0.01). The population was clustered in LH I (LH≤7.5 IU/l) and LH II (LH>7.5 IU/l). Correlation analysis showed significant LH correlations for TT (p<0.0001) and FT (p=0.0004) for LH I; significant LH correlation to FT (p=0.0001) for LH II. Simple linear regression showed that LH was significantly predicted by both TT (p-Value<0.0001) and FT (p-Value=0.0004) in LH I; but only FT (p-Value<0.0001) in LH II. Multiple linear regression showed that LH was significantly predicted by both TT (p-Value=0.0004) and PSA (p-Value=0.03) in LH I; but only by FT (p-Value=0.003) in LH II. Analysis of variance showed that: a) LH and age were significantly lower in LH I than II; b) LH I expressed higher mean FT levels (p=0.08) and lower mean P+ (p=0.07) than LH II. The LH versus PSA plot was computed for LH group I and 3 sub clusters were created: LH I group A (LH/PSA≤0.25), B (0.250.75). Correlation analysis showed that LH was significantly correlated to age (p=0.01), TT (p=0.03) and PSA (p=0.0004) in LH IA; LH was significantly correlated to PSA (p<0.0001) in LH IB; and LH significantly correlated to TT (p=0.005), FT (p=0.01), and PSA (p=0.008) in LH 1C. Multiple linear regression showed that LH was significantly correlated to age (p=0.02) and PSA (p=0.01) in LH IA, to TT (p=0.01) and PSA (p<0.0001) in LH IB, and to PSA (p=0.003) and weakly to TT (p=0.09) in LH IC. The groups differed significantly for mean levels of LH (p=0.0004), TT (p=0.005), FT (p=0.01), PSA (p<0.0001), bGS (p=0.003). Analysis of variance between the subgroups of the patient population (LH IA, LH IB, LH IC, LH II) showed significant differences in mean levels for LH (p<0.0001), age (p=0.004), TT (p=0.009), FT (p=0.02), PSA (p<0.0001), PSA/FT (p<0.0001), bGS (p=0.01), but not for P+ (p=0.10). CONCLUSION: According to LH physiopathology, the prostate cancer population could be clustered into hypo-gonadic and non-hypo-gonadic group at diagnosis. The hypo-gonadic group expresses an aggressive tumor phenotype and might be divided into two more different significant subsets including primary and secondary hypo-gonadic patients: the former (LH II) including older patients with high LH levels, the latter (LH IA) including younger patients with low LH and LH/PSA levels (subgroup LH IA). The non-hypo-gonadic group showed a less aggressive tumor phenotype and according to the LH/PSA ratio might beclustered into LH IB (0.250.75), the former showing a more aggressive tumor phenotype than the latter. Confirmatory studies are necessary.

Investigative clinical study on prostate cancer part III: exploring total PSA and free testosterone distributions and linear correlations in groups and subgroups of operated prostate cancer patients according to the total PSA/FT ratio.

OBJECTIVES: Prostate cancer is an interesting tumor for endocrine investigation. The prostate-specific antigen/free testosterone (PSA/FT) ratio has been shown to be effective in clustering patients in prognostic groups as follows: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40) and high risk (PSA/FT >0.40 and ≤1.5). In the present study we explored the total PSA and FT distributions, and linear regression of FT predicting PSA in the different groups (PSA/FT, pT and pG) and subgroups (pT and pG) of patients according to the prognostic PSA/FT ratio. PATIENTS AND METHODS: The study included 128 operated prostate cancer patients. Pretreatment simultaneous serum samples were obtained for measuring free testosterone (FT) and total PSA levels. Patients were grouped according to the total PSA/FT ratio prognostic clusters (≤0.20, >0.20 and ≤0.40, >0.40), pT (2, 3a and 3b+4) and pathological Gleason score (pG) (≤6, = 7 >3 + 4, ≥7 >4 + 3). The pT and pG sets were subgrouped according to the prognostic PSA/FT ratio. Linear regression analysis of FT predicting total PSA was computed according to the different PSA/FT prognostic clusters for the: (1) total sample population, (2) pT and pG groups, (3) intraprostatic (pT2) and extraprostatic disease (pT3a/3b/4), and (4) low-intermediate grade (pG ≤6) and high-grade (pG ≥7) prostate cancer. RESULTS: Analysis of variance always showed highly significant different PSA distributions for (1) the different PSA/FT, pT and pG groups; and (2) the pT and pG prognostic subgroups. Significant FT distributions were detected for the (1) PSA/FT and pT groups; and (2) the pT2, pT3a and pG ≤6 prognostic PSA/FT subgroups. Correlation, variance and linear regression analysis of FT predicting total PSA was significant for (1) the PSA/FT prognostic clusters, (2) all the pT2 and pT3a subgroups, and (3) the pT3b/4 subgroup with PSA/FT >0.20 and ≤0.40, and (4) all the pG subsets. Linear regression analysis showed that the slopes of the predicting variable (FT) were always highly significant for patients with (1) intraprostate and extraprostate disease, and (2) low-grade and high-grade prostate cancer. CONCLUSIONS: According to the prognostic PSA/FT ratio, significantly lower levels of FT are detected in prostate cancer patients with extensive and high-grade disease. Also, significant linear correlations of FT predicting PSA are assessed in the different groups and subgroups of patients clustered according to the prognostic PSA/FT ratio. Confirmatory studies are needed.

Investigative clinical study on prostate cancer part II: on the role of the pretreatment total PSA to free testosterone ratio as a marker assessing prostate cancer prognostic groups after radical retropubic prostatectomy.

OBJECTIVES: To explore the significance of the pretreatment total prostate-specific antigen (PSA) to free testosterone (FT) ratio (PSA/FT) as a marker for assessing the pathologic Gleason sum (pGS) and levels of tumor extension (pT) in prostatectomy specimens. PATIENTS AND METHODS: 128 of 135 consecutive patients diagnosed with prostate cancer underwent radical prostatectomy. Simultaneous pretreatment serum samples were obtained to measure serum total testosterone, FT and total PSA levels. The statistical design of the study included 2 sections: the first part trying to explore the role of the PSA/FT ratio in clustering patients with different pathologic prognostic factors, and the second to investigate the PSA/FT ratio distribution in different groups of patients according to the pathologic stage and pGS of the specimen after radical prostatectomy. RESULTS: The average age was 65.80 (range 51.21-77.26) years, mean PSA was 8.88 (range 1.22-44.27) µg/l, mean FT was 35.32 (range 13.70-69.30) pmol/l, and the mean PSA/FT ratio was 0.27 (range 0.04-1.48). The PSA/FT ratio significantly clustered both the pT and pGS groups. Analysis of variance for the distribution of the PSA/FT ratio was significant for the pT model groups. The mean PSA/FT ratio increased as the tumor extended and grew through the prostate gland (high-stage disease). Analysis of variance for the different distributions of the PSA/FT ratio was significant for all model pGS groups. In our investigation we also found (data not shown) that a PSA/FT ratio of ≥0.40 was strongly correlated with large extensive (pT3b+pT4) and high-grade cancers (pGS8+pGS9). CONCLUSIONS: Prostate cancer patients may be classified into 3 different pathologic prognostic groups according to the PSA/FT ratio: low risk (PSA/FT ≤0.20), intermediate risk (PSA/FT >0.20 and ≤0.40), and high risk (PSA/FT >0.40 and ≤1.5). The PSA/FT ratio may be considered as the marker expressing different biology groups of prostate cancer patients, and it is strongly associated with pT and pGS.

Investigative clinical study on prostate cancer: on the role of the pretreatment total PSA to free testosterone ratio in selecting different biology groups of prostate cancer patients.

OBJECTIVES: To show that prostate cancer biology is related to serum levels of both free testosterone (FT) and prostate-specific antigen (PSA), that PSA level is linearly related to FT and that the PSA to FT ratio may be considered as the growth rate parameter expressing cancer phenotype biology. MATERIALS AND METHODS: The study includes 135 consecutive patients diagnosed with prostate cancer. Pretreatment simultaneous serum samples for analyzing total testosterone (TT), FT and total PSA levels were obtained. The study was assessed according to a multidimensional approach of the five continuous variables including TT, FT, PSA, AGE and percentage of positive biopsies (=P+). The all sets of data were considered as one--sample with no groupings among the observations. Multivariate analysis included factor analysis (FA) and principal component analysis (PCA). Multivariate inferential statistics for comparing different groups of patients according to the PSA to free testosterone ratio (PSA/FT) included Hotteling's multivariate two-sample T²-Test for comparing two mean vectors as well as Box's M-Test with the chi-square approximation for comparing multiple covariance matrices when patients were sampled in more than two groups. RESULTS: Factor analysis showed the two natural grouping of variables, FT-TT and PSA-P+. PCA assessed FT and PSA as the two variables with large variances having a notable influence on the first two principal components. Multiple linear regression analysis showed that all the income variables, except age, significantly predicted the PSA/FT ratio. Patients were first sampled according to the PSA/FT ratio in group 1 (PSA/FT ≤ 0.20) and group 2 (PSA/FT > 0.20), and Hotteling's multivariate two sample T²-Test was significant (P < 0.01). Patients were then sampled according to the PSA/FT ratio in group 1 (PSA/FT ≤ 0.20), group 2 (PSA/FT > 0.20 and ≤ 0.40), and group 3 (PSA/FT > 0.40), and Box's M-Test comparing the covariance matrices of the 3 groups differed significantly (P < 0.001). Finally, patients were sampled according to the PSA/FT ratio in 6 groups, and Box's M-Test was again significant (P < 0.001). CONCLUSIONS: The PSA to FT ratio is the growing rate parameter expressing different biology patterns and assessing different groups of prostate cancer patients. In our opinion, the results of the present study might have wide applications in understanding, assessing and planning prostate cancer studies including basic science, screening, assessing risk of the disease, predicting disease stage as well natural history after a planned treatment involving biochemical recurrence, progression, hormone refractory prostate cancer and disease-specific survival.

Intraparenchymal renal artery aneurysms. Case report with review and update of the literature.

Increased interest in aneurysms involving the renal artery and its branches has occurred during the past 3 decades. The prevalence of renal artery aneurysms is approximately 0.01%-1% in the general population as well as 2.5% in hypertensive patients undergoing angiography. Intraparenchymal renal artery aneurysms (IPRAAs) are rare since being detected in less than 10% of patients with renal artery aneurysms. The Authors report an unusual case of multiple small intrarenal artery aneurysms associated with a large IPRAA located in the mid portion of the right kidney. Usually, IPRAAs are secondary to diseases or injuries of the kidney vascular network. They are classified as true, false, saccular, fusiform, dissecting, and microaneurysms. Potential complications of IPRAAs include peripheral dissection, thrombosis, hypertension, renal infarction and rupture. IRAAs may be detected incidentally as well as present with urologic symptoms and signs related to complications. Actually, IRAAs are investigated by non invasive modalities including duplex ultrasound, magnetic resonance angiography, spiral three-dimensional computed tomography angiography, and three-dimensional reconstructed rotational digital substraction angiography of the segmental and distant branches of the renal artery. Angiography with intrarterial injection of contrast material is the gold standard in diagnosing IPRAAs. Treatment options for IPRAAs include observation, aneurysmectomy with surgical repair, endovascular procedures, nephrectomy or partial nephrectomy. Observation is indicated for asymptomatic intraparenchymal renal artery aneurysms measuring less than 2 cm in diameter. Surgical repair of IPRAAs includes aneurysmectomy and reconstruction of the renal artery by in vivo or ex vivo technique. The procedure is indicated for IPRAAs causing renovascular hypertension, dissection, urologic symptoms, embolization, local expansion and women of childbearing age with a potential for pregnancy. In recent years, transcatheter arterial embolization has emerged as a simple, useful and effective technique in managing IRAAs. The procedure is performed by transfemoral catheterization as well as by superselective catheterization and embolization of interlobar arteries with 3F microcatheters. Endovascular occlusion is obtained by using gelatin sponge, steel coils, detachable baloons, and conventional non-detachable microcoils delivered through a microcatheter. Nephrectomy or partial nephrectomy are reserved for conditions precluding renal revascularization which include overt RAA rupture, covert RAA rupture, artery-to-vein fistula, renal cell carcinoma, end stage nephropaty, renal infarction, severe ischemic renal atrophy or complex intrarenal aneurysms. Recently, partial nephrectomy by the laparoscopic approach has been proposed for managing IPRAAs and the procedure is considered feasible and safe.

Primary lymphoepithelioma-like carcinoma of the urinary bladder: report of one case with review and update of the literature after a pooled analysis of 43 patients.

BACKGROUND AND OBJECTIVES: Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated epithelial tumor with a dense inflammatory infiltrate that resembles the lymphoepithelioma of the nasopharinx occurring in other sites. Primary LELC of the bladder (LELCB) was first reported by Zukerberg et al in 1991. The incidence of LELCB is 0.4%-1.3% of all bladder carcinomas. The mean age at diagnosis is 69 years. Of the patient population 69% are men. Herein we report on one more case of primary predominant LELCB and review all the English literature concerning this subject after performing a pooled analysis of the cases recorded in the English literature including the present one. MATERIALS AND METHODS: The reports of 43 patients including the present case of primary LELCB from the English literature were collected from 1991 to 2002. Patients were evaluated for age, sex, primary and adjuvant treatments, clinical staging, follow-up and outcome, and disease related survival. The overall patient population was separated into 3 groups according to the LELCB classification of Amin. RESULTS: The overall patient population included 31 males and 12 females. Average age was 68.4 years (range 52-84). LELCB histological subtypes resulted pure in 17 cases (40%), predominant in 16 (37%) and focal in 10 (23%). Mean follow-up was 37.7 months (range 0-216). Outcome resulted as follows: 26 patients (62%) did not show evidence of diasease, 11 (26%) died of disease, 1 (2%) was alive with metastases, and 4 (10%) died for causes unrelated to the primary disease. Survival rate related to specific disease resulted 71%. Mean follow-up was 48.1 in the first group (pure LELCB), 32 in the second (predominant LELCB), and 30.3 in the third one (focal LELCB). Patients with not evidence of disease were 13 (81%) in group 1, 13 (82%) in group 2, and 0 in group 3. Patients who died of their disease resulted 1 (6%) in the first group, 1 (6%) in the second, and 9 (90%) in the third one. Patients who died for disease not related to the primary tumor were 2 (13%) in the first group, 1 (6%) in the second, and 1 (10%) in the third one. One patient (6%) was alive with metastases in group 2. Survival rate related to specific disease resulted 93% in the first group, 93% in the second one, and 0% in the third one. CONCLUSIONS: To date, there are no clear guide lines for the treatment of LELCB. Treatments performed include both deep transurethral resection of the tumor (TUR-B) as well as partial or radical cystectomy, with or without adjuvant treatments including systemic chemotherapy and radiotherapy. The prognosis is favorable for patients presenting with the pure and predominant forms with a diploid DNA pattern and very poor for patients presenting with focal LELCB. Bladder salvage therapy by performing both TUR-B alone or combined with adjuvant systemic chemotherapy may be a reasonable option for patients with pure or predominant LELCB, while radical surgery with adjuvant systemic therapy may be indicated for focal muscle invasive LELCB.

Vesicouterine fistulas following cesarean section: report on a case, review and update of the literature.

Herein we report on 1 more case of vesicouterine fistula following cesarean section with review and update of the literature concerning this unusual topic. The disease presented with vaginal urinary leakage, cyclic hematuria and amenorrhea. The fistula was successfully repaired by delayed surgery. Actually, all over the world the prevalence of the disease is increasing for the frequent use of the cesarean section. Fistulas may develop immediately after a cesarean section, manifest in the late puerperium or occur after repeated procedures. Spontaneous healing is reported in 5% of cases. Vesicouterine fistulas present with vaginal urinary leakage, cyclic hematuira (menouria), amenorrhea, infertility, and first trimester abortions. The diagnosis is ruled out by showing the fistulous track between bladder and uterus as well as by excluding other more frequent urogenital fistulas. The disease treatment options include conservative treatment as well as surgical repair. Rarely, patients refuse any kind of treatment because of the benignity of symptoms and prognosis of the disease. Conservative management by bladder catheterization for at least 4-8 weeks is indicated when the fistula is discoveredjust after delivery since there is good chance for spontaneous closure of the fistulous track. Hormonal management should be tried in women presenting with Youssef's syndrome. Surgery is the maninstay and definitive treatment of vesicouterine fistulas after cesarean section. Patients scheduled for surgery should undergo pretreatment of urinary tract infections. Surgical repair of vesico-uterine fistulas are performed by different approaches which include the vaginal, transvesical-retroperitoneal and transperitoneal access which is considered the most effective with the lowest relapse rate. Recently, laparoscopy has been proposed as a valid option for repairing vesicouterine fistulas. The endoscopic treatment may be effective in treating small vesicouterine fistulas. The pregnancy rate after repair is 31.25% with a rate of term deliveries of 25%. The disease may be prevented by emptying the bladder as well as by carefully dissecting the lower uterine segment. It is advisable that after vesicouterine fistula repair delivery should be performed by repeating a cesarean section since the risk of fistula recurrence. Usually, vesicouterine fistulas are diagnosed postoperatively. As a result, at least 95% of patients will undergo another operation for repairing the fistula. In the meantime they are bothered by related symptoms which impair their quality of life. As far as we are concerned intraoperative diagnosis is the gold standard in detecting vesicouterine fistulas for allowing immediate repair. We propose intraoperative sonography by the transvaginal (or transrectal) route for the Foley transurethral catheter producing bloody urine, for suspecting bladder injury while dissecting the uterine lower segment and for monitoring patients who already had had vesicouterine fistula repair. As a result patients will avoid the familial and social problems related to the disease as well another operation. Moreover, ultrasound Doppler examination may help in better investigating and understanding the pathophysiology of vesicouterine fistulas.