Carmelo Monaco

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 followingcesarean section with review and update of the literature concerningthis unusual topic. The disease presented with vaginal urinary leakage,cyclic hematuria and amenorrhea. The fistula was successfully repairedby delayed surgery. Actually, all over the world the prevalence of thedisease is increasing for the frequent use of the cesarean section.Fistulas may develop immediately after a cesarean section, manifest inthe late puerperium or occur after repeated procedures. Spontaneoushealing is reported in 5% of cases. Vesicouterine fistulaspresent with vaginal urinary leakage, cyclic hematuira (menouria),amenorrhea, infertility, and first trimester abortions. The diagnosis isruled out by showing the fistulous track between bladder and uterus aswell as by excluding other more frequent urogenital fistulas. Thedisease treatment options include conservative treatment as well assurgical repair. Rarely, patients refuse any kind of treatment becauseof the benignity of symptoms and prognosis of the disease. Conservativemanagement by bladder catheterization for at least 4–8 weeks isindicated when the fistula is discovered just after delivery since thereis good chance for spontaneous closure of the fistulous track. Hormonalmanagement should be tried in women presenting with Youssefs syndrome.Surgery is the maninstay and definitive treatment of vesicouterinefistulas after cesarean section. Patients scheduled for surgery shouldundergo pretreatment of urinary tract infections. Surgical repair ofvesico-uterine fistulas are performed by different approaches whichinclude the vaginal, transvesical-retroperitoneal and transperitonealaccess which is considered the most effective with the lowest relapserate. Recently, laparoscopy has been proposed as a valid option forrepairing vesicouterine fistulas. The endoscopic treatment may beeffective in treating small vesicouterine fistulas. The pregnancy rateafter repair is 31.25% with a rate of term deliveries of25%. The disease may be prevented by emptying the bladder as wellas by carefully dissecting the lower uterine segment. It is advisablethat after vesicouterine fistula repair delivery should be performed byrepeating a cesarean section since the risk of fistula recurrence.Usually, vesicouterine fistulas are diagnosed postoperatively. As aresult, at least 95% of patients will undergo another operationfor repairing the fistula. In the meantime they are bothered by relatedsymptoms which impair their quality of life. As far as we are concernedintraoperative diagnosis is the gold standard in detecting vesicouterinefistulas for allowing immediate repair. We propose intraoperativesonography by the transvaginal (or transrectal) route for the Foleytransurethral catheter producing bloody urine, for suspecting bladderinjury while dissecting the uterine lower segment and for monitoringpatients who already had had vesicouterine fistula repair. As a resultpatients will avoid the familial and social problems related to thedisease as well another operation. Moreover, ultrasound Dopplerexamination may help in better investigating and understanding thepathophysiology of vesicouterine fistulas.

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

Increased interest in aneurysms involving therenal artery and its branches has occurredduring the past 3 decades. The prevalence ofrenal artery aneurysms is approximately 0.01%–1% in the general population as well as2.5% in hypertensive patients undergoingangiography. Intraparenchymal renal arteryaneurysms (IPRAAs) are rare since beingdetected in less than 10% of patients withrenal artery aneurysms. The Authorsreport an unusual case of multiple smallintrarenal artery aneurysms associatedwith a large IPRAA located in the mid portionof the right kidney. Usually, IPRAAs aresecondary to diseases or injuries of the kidneyvascular network. They are classified as true,false, saccular, fusiform, dissecting, andmicroaneurysms. Potential complications ofIPRAAs include peripheral dissection,thrombosis, hypertension, renal infarction andrupture. IRAAs may be detected incidentally aswell as present with urologic symptoms andsigns related to complications. Actually, IRAAsare investigated by non invasive modalitiesincluding duplex ultrasound, magnetic resonanceangiography, spiral three-dimensional computedtomography angiography, and three-dimensionalreconstructed rotational digital substractionangiography of the segmental and distantbranches of the renal artery. Angiography withintrarterial injection of contrast material isthe gold standard in diagnosing IPRAAs.Treatment options for IPRAAs includeobservation, aneurysmectomy with surgicalrepair, endovascular procedures, nephrectomy orpartial nephrectomy. Observation is indicatedfor asymptomatic intraparenchymal renal arteryaneurysms measuring less than 2 cm in diameter.Surgical repair of IPRAAs includesaneurysmectomy and reconstruction of the renalartery by in vivo or ex vivo technique. Theprocedure is indicated for IPRAAs causingrenovascular hypertension, dissection, urologicsymptoms, embolization, local expansion andwomen of childbearing age with a potential forpregnancy. In recent years, transcatheterarterial embolization has emerged as a simple,useful and effective technique in managingIRAAs. The procedure is performed bytransfemoral catheterization as well as bysuperselective catheterization and embolizationof interlobar arteries with 3F microcatheters.Endovascular occlusion is obtained by usinggelatin sponge, steel coils, detachablebaloons, and conventional non-detachablemicrocoils delivered through a microcatheter.Nephrectomy or partial nephrectomy are reservedfor conditions precluding renalrevascularization which include overt RAArupture, covert RAA rupture, artery-to-veinfistula, renal cell carcinoma, end stagenephropaty, renal infarction, severe ischemicrenal atrophy or complex intrarenal aneurysms.Recently, partial nephrectomy by thelaparoscopic approach has been proposed formanaging IPRAAs and the procedure is consideredfeasible and safe.

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.

Chronic inflammation of the prostate type IV with respect to risk of prostate cancer

BACKGROUND Chronic inflammatory infiltrate (CII) might be involved in prostate cancer (PCA) and benign hyperplasia (BPH); however, its significance is controversial. Chronic inflammatory prostatitis type IV is the most common non cancer diagnosis in men undergoing biopsy because of suspected PCA. OBJECTIVE To evaluate potential associations of coexistent CII and PCA in biopsy specimens after prostate assessment. DESIGN, SETTING, AND PARTICIPANTS Between January 2007 and December 2008, 415 consecutive patients who underwent prostate biopsy were retrospectively evaluated. The investigated variables included Age (years) and PSA (ug/l); moreover, CII+, glandular atrophy (GA+), glandular hyperplasia (GH+), prostate Intraepithelial neoplasm (PIN+), atypical small acinar cell proliferation (ASAP+) and PCA positive cores (P+) were evaluated as categorical and continuous (proportion of positive cores). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Associations of CII+ and PCA risk were assessed by statistical methods. RESULTS AND LIMITATIONS In the patient population, a biopsy core positive for PCA was detected in 34.2% of cases and the rate of high grade PCA (HGPCA: bGS ! 8) resulted 4.82%. CII+ significantly and inversely associated with a positive biopsy core P+ (P < 0.0001; OR = 0.26) and HGPCA (P = 0.0005; OR = 0.05). Moreover, the associations indicated that patients with coexistent CII+ on needle biopsy were 74% less likely to have coexistent PCA than men without CII+ as well as 95% less likely to have HGPCA in the biopsy core than men without coexistent CII+. There were limits in our study which was single centre and included only one dedicated pathologist. CONCLUSIONS There was an inverse association of chronic inflammation of the prostate type IV and risk of PCA; moreover, HGPCA was less likely to be detected in cancers associated with coexistent CII. In prostate microenvironment, prostate chronic inflammation may be protective; however, its role in PCA carcinogenesis remains controversial and needs further research.

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 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<FSH/PSA≤1.61) and C (1.61<FSH/PSA≤19.4). The model was assessed by simple linear and multiple linear regression analysis and differences between the groups were assessed by analysis of variance. Results: In the patient population, FSH correlated to LH (p < 0.0001), FT (p = 0.007) and age (p = 0.004). FSH was independently predicted by both LH (p < 0.0001) and PSA (p = 0.04). PSA predicted FSH/PSA A (p < 0.0001), B (p < 0.0001) and C (p = 0.04). On multiple regression analysis, FSH/PSA A was predicted by PSA (p < 0.0001), P+ (p = 0.03) and bGS (p = 0.04); FSH/PSA B by LH (p = 0.002) and PSA (p < 0.0001); FSH/PSA C by LH (p < 0.0001) and PSA (p < 0.0001). Moreover, FSH/PSA A, B and C differed for mean values of FSH (p < 0.0001), LH (p < 0.0001), PSA (p < 0.0001) and PSA/FT ratio (p < 0.0001). FSH/PSA clusters showed features of decreasing aggressive disease as the FSH/PSA ratio progressed from A to C. Conclusion:At the diagnosis of prostate cancer and along the pituitary-testis-prostate axis in a patient population FSH significantly correlated to LH, FT and age, and FSH was independently and significantly predicted by both LH and PSA. Because of the independent prediction of PSA by FSH, the prostate cancer population at diagnosis was clustered and ranked according to the FSH/PSA ratio in groups A, B and C. Also, the predictive model of PSA on FSH for the different groups proved to be effective at selecting potential prognostic clusters in which the risk of progression might be assessed as low (group C), intermediate (group B) and high (group A). The FSH/PSA model might be considered as a tool for prostate cancer study and for use in individualized, risk-adapted approaches. However, confirmatory studies are needed.

Acute pyelonephritis causing acute renal allograft dysfunction

In renal transplant recipients, acute pyelonephritis may cause acute deterioration of renal function. We report a case with acute allograft failure due to acute pyelonephritis, which was confirmed by graft biopsy. After appropriate antimicrobial therapy, allograft function recovered.

Simultaneous Measurements of Follicle Stimulating Hormone and Total Testosterone and Associations in Clinically Localized Prostate Cancer

Objectives: To evaluate the potential relations of simultaneous measurements of basal levels of follicle stimulating hormone (FSH) and total testosterone (TT) in clinically localized prostate cancer (PCa). Materials and Methods: The study included 126 patients who had simultaneous measurements of prostate specific antigen (PSA), FSH, and TT before undergoing radical prostatectomy for clinically localized PCa. Correlations and independent associations between clinical and pathological factors were investigated by statistical methods. Results: The tumor volume (TV) was directly correlated to PSA and TT which was inversely related to FSH. Moreover, it was independently associated with both PSA and TT. In a multivariate linear regression model, FSH and TV were simultaneous independent factors associated with TT, and the association was inverse in the former and direct in the latter. In the patient population, the subset with FSH levels above the third quartile was related to lower median levels of TT that were associated with high grade cancer showing a lower TV. In localized PCa, basal levels of TT were associated with tumor parameters and inversely related to FSH levels, and the subset FSH levels above the third quartile were related to lower TT levels that were associated with high grade cancers showing a lower tumor load. Conclusion: Preoperative TT was associated with tumor parameters and inversely related to FSH levels. Patient with increased FSH levels was related to lower levels of TT, which was associated with high grade cancer.

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 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 inihibitors, 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.