Open versus laparoscopic partial nephrectomy for clinical T1a renal masses: a matched-pair comparison of 280 patients with TRIFECTA outcomes (RECORd Project).

AIM OF THE STUDY: To report a matched-pair comparative analysis between open (OPN) and laparoscopic partial nephrectomy (LPN) for clinical (c) T1a renal masses from a large prospective multicenter dataset. MATERIALS AND METHODS: The RECORd Project includes all patients who underwent OPN and LPN for kidney cancer between January 2009 and January 2011 at 19 Italian centers. Open and laparoscopic groups were compared regarding clinical, surgical, pathologic, functional results and TRIFECTA outcome. Multivariable logistic regression models were used to analyze predictors of WIT >25 min, surgical complications (SC) and the achievement of the TRIFECTA outcome. RESULTS: Overall, 301 patients had OPN and 149 LPN. Groups were matched 1:1 (140 matched pairs) for clinical diameter, tumor location and type of indication. Laparoscopic partial nephrectomy was associated with a significantly mean longer WIT (19.9 vs. 15.1 min; p < 0.001), and it was an independent predictor of a WIT >25 min (RR 6.29, p < 0.0001). The TRIFECTA was achieved in 78.6 and 74.3% after OPN and LPN (p = ns), respectively, and the surgical approach was not a predictor of a negative TRIFECTA and SC at multivariable analysis. At 6-month follow-up, no significant differences were observed between the OPN and LPN group both in estimated glomerular filtration rate (eGFR) (∆GFR 1.1 vs. 4.1 mL/min) and in new-onset stage III-V chronic kidney disease (CKD) rate (0 vs. 0.7%). CONCLUSION: No significant difference in achieving the TRIFECTA outcome was reported after OPN and LPN. LPN was associated with a significantly longer WIT. However, eGFR at 6-month follow-up did not differ significantly between the two surgical approaches.

Different muscarinic receptor subtypes modulate proliferation of primary human detrusor smooth muscle cells via Akt/PI3K and map kinases.

While acetylcholine (ACh) and muscarinic receptors in the bladder are mainly known for their role in the regulation of smooth muscle contractility, in other tissues they are involved in tissue remodelling and promote cell growth and proliferation. In the present study we have used primary cultures of human detrusor smooth muscle cells (HDSMCs), in order to investigate the role of muscarinic receptors in HDSMC proliferation. Samples were obtained as discarded tissue from men >65 years undergoing radical cystectomy for bladder cancer and cut in pieces that were either immediately frozen or placed in culture medium for the cell culture establishment. HDSMCs were isolated from samples, propagated and maintained in culture. [(3)H]-QNB radioligand binding on biopsies revealed the presence of muscarinic receptors, with a Kd of 0.10±0.02nM and a Bmax of 72.8±0.1fmol/mg protein. The relative expression of muscarinic receptor subtypes, based on Q-RT-PCR, was similar in biopsies and HDSMC with a rank order of M2≥M3>M1>M4>M5. The cholinergic agonist carbachol (CCh, 1-100µM) concentration-dependently increased [(3)H]-thymidine incorporation (up to 46±4%). This was concentration-dependently inhibited by the general muscarinic receptor antagonist atropine and by subtype-preferring antagonists with an order of potency of darifenacin >4-DAMP>AF-DX 116. The CCh-induced cell proliferation was blocked by selective PI-3 kinase and ERK activation inhibitors, strongly suggesting that these intracellular pathways mediate, at least in part, the muscarinic receptor-mediated cell proliferation. This work shows that M2 and M3 receptors can mediate not only HDSM contraction but also proliferation; they may also contribute bladder remodelling including detrusor hypertrophy.

Role of F18-FDG-PET/CT in restaging patients affected by renal carcinoma.

BACKGROUND: Renalcancers account for around 3% of all cancers and the most common type of (90%) is renal cell carcinoma Five-year survival rate in renal cancer patients is 68.4%. AIM: The aim of our study was to establish the role of F18-FDG-PET/CT in restaging patients with renal carcinoma who underwent partial or radical nephrectomy. Secondary aim of the study was to identify histological characteristics of the primary tumour that may be responsible for the metabolic behaviour of neoplastic lesions. MATERIALS AND METHODS: We retrospectively evaluated 68 patients with renal carcinoma in whom F18-FDG-PET/CT was performed. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of F18-FDG PET/CT were 82%, 100%, 100%, 66.7% and 86.8%, respectively. CONCLUSIONS: The results of our study suggest that F18-FDG PET/CT is characterised by high specificity and positive predictive value and can be useful in restaging patients affected by renal carcinoma. However, due to low negative predictive value, this method cannot be recommended for definitely ruling out suspected disease relapse.

Pre-existing type-2 diabetes is not an adverse prognostic factor in patients with renal cell carcinoma: a single-center retrospective study.

OBJECTIVES: Type-2 diabetes mellitus (DM) is a metabolic disease affecting several million people all over the world. The correlation between DM and malignancies is well established due to the findings of several large population-based studies. However, for endometrial, breast, colorectal, and liver cancers it has also been reported that DM could exert a negative impact on prognosis, causing a significant reduction in cancer-specific survival. A significant correlation with DM has also been demonstrated in renal cell carcinoma (RCC), but the possible prognostic role of DM in this setting has been poorly investigated and remains controversial. This study provides a retrospective analysis of a single-center surgical series with the aim of assessing the features and prognosis of RCC in DM patients. MATERIALS AND METHODS: Since 1987 a prospectively compiled database at our institute has collected the data of 1,761 patients who underwent surgery for RCC. All the patients are followed in a specially dedicated out-patient ambulatory. For this study, patients who were taking insulin or oral anti-hyperglycemic drugs before surgery for RCC were considered as DM cases. Their clinical and pathologic features were compared with those of patients without DM. Then, limiting the analysis to non-metastatic patients, the Kaplan-Meier method was used to calculate survival functions and univariable and multivariable Cox regression models addressed time to RCC-related and non RCC-related mortality. RESULTS: The data of 1,604 patients without DM and 157 with DM (prevalence 8.9%) have been analyzed; the latter were more frequently males, older, and with higher co-morbidity and with more asymptomatic, smaller, and low stage neoplasms, though with a higher grading. After a median follow-up time of 53.4 months (IQR 20-97 months), the factors that influenced RCC-related mortality were the presence of symptoms at diagnosis, tumor size, TMN staging, and grading, while those that influenced non-RCC-related mortality were age, gender, and co-morbidities, whereas the presence of DM showed no influence at all. Moreover, in patients without and with DM, progression rate (19.8% vs. 15.1%, P = 0.195) and RCC-related mortality rate (9.6% vs. 5.3%, P = 0.102) were also statistically equivalent. CONCLUSION: In our experience, the prevalence of DM in RCC patients is close to 10%. Such a condition does not determine any significant influence on prognosis of RCC.

A comparison of hexaminolevulinate (Hexvix(®)) fluorescence cystoscopy and white-light cystoscopy for detection of bladder cancer: results of the HeRo observational study.

BACKGROUND: To date, no study has presented results of photodynamic diagnosis (PDD) cystoscopy compared with white-light cystoscopy (WLC) in daily practice. The aim of the present study is to evaluate the diagnostic accuracy of hexylaminolevulinate hydrochloride (Hexvix(®)) PDD cystoscopy compared with standard WLC used in daily practice. METHODS: An observational, open-label, comparative, controlled (within patient), multicenter study was carried out on 96 consecutive patients with suspected or confirmed bladder cancer. All patients had standard WLC followed by blue-light cystoscopy (BLC). Positive lesions detected using WLC and BLC were recorded. Biopsies/resection of each positive lesion were taken after the bladder was inspected. Sensitivity, specificity, positive predictive value, and negative predictive value with each method were calculated. RESULTS: Overall, 234 suspicious lesions were detected; 108 (46.2%) were histologically confirmed to be bladder tumors/carcinoma in situ (CIS). The sensitivity of BLC biopsies was significantly higher than for WLC technique (99.1 vs 76.8%; p < 0.00001). The relative sensitivity of BLC versus WLC was 1.289, showing superiority of BLC of 28.9%. The specificity of BLC biopsies was not significantly different compared with WLC (36.5 vs 30.2%). Positive predictive value for BLC- and WLC-guided biopsies was 54.9 and 50.9%, respectively. Negative predictive value per biopsy for BLC- and WLC-guided biopsies was 97.4 and 64.8%, respectively. BLC and WLC reached the correct diagnosis in 97.9 and 88.5% of patients, respectively. This difference was statistically significant (p = 0.0265). The lack of a random biopsy protocol was the major limitation of the study. CONCLUSIONS: Hexvix(®) PDD cystoscopy used in daily practice enhances the diagnostic accuracy of standard cystoscopy with higher negative predictive value, potentially permitting an improvement in patient prognosis.

Prognostic factors in a large multi-institutional series of papillary renal cell carcinoma.

OBJECTIVES: To investigate cancer-related outcomes and prognostic factors of papillary renal cell carcinoma (pRCC) in a large multicentre data set. Oncological outcome and prognostic factors of pRCC have been limitedly evaluated in comparison with the most common RCC subtype, clear cell RCC. PATIENTS AND METHODS: From a multicentre retrospective database, including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007, 577 patients with pRCC were identified. Univariable and multivariable Cox regression models were performed to identify prognostic factors predictive of recurrence-free survival (RFS) and cancer-specific survival (CSS) after surgery. RESULTS: At a median (interquartile range) follow-up of 39.2 (21.7-72) months, 81 (14%) patients had experienced disease progression and 63 (11%) patients had died from disease; the 5-year RFS estimate was 85.5%. In multivariable analysis, pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.9; P= 0.007) and Fuhrman nuclear grade (pooled P= 0.039) were all independent predictors of RFS; the 5-year CSS estimate was 87.9%. In Cox multivariable analysis, an independent predictive role was reconfirmed for mode of presentation (pooled P= 0.038), pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.4; P= 0.049) and Fuhrman nuclear grade (pooled P= 0.037). CONCLUSIONS: Patients with pRCC have a low risk of tumour recurrence and cancer-related death after surgery. Fuhrman nuclear grade was found to be a stronger predictor of both RFS and CSS, whereas only a non-statistically significant trend was found for the 2009 pathological T stage.

[ProACT (Adjustable Continence Therapy) implants in case of failure of other techniques for urinary incontinence]. / Reimpianto del sistema ProACT in caso di fallimento precoce nella cura dell'incontinenza urinaria dopo prostatectomia radicale.

BACKGROUND: Urinary incontinence after radical prostatectomy is one of the most feared problems. It can affect almost 40% of patients, with different degrees of severity according to each specific case. The aim of this work is to analyze our experience in ProACT (Adjustable Continence Therapy) implants, especially in case of failure of other techniques. METHODS: Between November 2007 and December 2010, 31 patients with post-radical prostatectomy incontinence underwent a ProACT implant. Eight patients had their device explanted (in local anesthesia): in two cases the device spontaneously broke, three of them migrated in the urethra (one patient received radiation therapy), another one was infected in the device site (one in BCG treatment for non-muscle invasive bladder cancer), two devices were wrongly placed. Seven of these patients had had their device replaced with success. Using pad score, incontinence was classified as mild, moderate and severe. Overall, the total amount of procedures, most of them fluoroscopic-guided in spinal anesthesia, were 38; the average duration of the surgery was 37.6 minutes. In one patient with impaired balloon volume due to monolateral device malfunction, we noticed good results in controlling incontinence; therefore, we successfully applied the same technique in other four cases with previous partial results. RESULTS: With a total amount of 28 implants, we had 17 (60.7%) complete responses, 6 (25%) partial and 4 (14.3%) failures. We had 4 post-radiotherapy implants: one was completely dry, two were in balloon adjustment, and one of them had a replacement due to urethral erosion of the first implant.
All patients with impaired balloon inflation were satisfied: one was completely dry and three had sensible improvement. CONCLUSIONS: The ProACT is a minimally invasive surgical therapy for post-radical prostatectomy urinary incontinence. Early failure is frequent and is mainly due to rupture and migration of the device. In these cases the solution can be the replacement, even with impaired balloon inflation.

[Sliding-clip robotic nephropexy]. / Sliding-clip robotic nephropexy.

BACKGROUND: Nephroptosis is a clinical condition characterized by an abnormal caudal movement of the kidney that descends more than 2 vertebral bodies (or more than 5 cm) during a position change from supine to upright. In the last decade, the availability of laparoscopic surgery has led to a revival of interest in nephroptosis and nephropexy. We describe our technique for transperitoneal laparoscopic robotic-assisted nephropexy. METHODS: The surgery was performed on a 78-year-old woman with a BMI of 18 and ASA 2. The diagnosis of nephroptosis was preoperatively confirmed by excretory urography in the supine and upright positions. The patient was placed in Trendelemburg position on the left side. The laparoscopic surgery was performed, through a transperitoneal approach, using the daVinci system: the ptosic kidney was fixed using two separated stiches of non-absorbable prolene 2.0 between the superior surface of the kidney and the quadratus lumborum muscle. The sutures were fixed using Hem-o-lok clips. RESULTS: Intra- or post-operative complications have not occurred. The effectiveness of treatment was demonstrated by an intravenous urography 60 days after. CONCLUSIONS: Robotic-assisted nephropexy is a safe and effective procedure that leads to both clinical and aesthetic excellent results, comparable to the ones obtained with the laparoscopic approach for the treatment of symptomatic renal ptosis. The robotic-assisted nephropexy appears to be easier, with the particular advantages of the intracorporeal suturing and a better intraoperative view; the sliding-clips method allows reducing the organ trauma to the minimum.

[Radiotherapy in case of locally advanced prostate cancer: long-term follow-up in 223 patients]. / La neoplasia prostatica localmente avanzata sottoposta a radioterapia: follow-up a lungo termine in 223 pazienti

AIM OF THE STUDY: To evaluate the long-term follow-up in patients undergoing external beam radiotherapy for locally advanced prostate cancer. PATIENTS AND METHODS: From November 1999 to January 2007, 223 patients with a histologic diagnosis (204 transperineal needle biopsies; 19 trans-urethral prostatic resections) of locally advanced prostate cancer underwent external beam radiotherapy; of these patients, 151 were T3a (extracapsular extension) and 72 were T3b (involvement of seminal vesicles); the extracapsular extension was demonstrated using pelvic RMN or transrectal ultrasound, while the presence of distant and lymph node metastases was excluded using TC total body or bone scan. PSA value at diagnosis was 29.1 ng/mL (0.4-379 ng/mL). Radiotherapy was used on prostate and seminal vesicles in 201 patients (141 T3a; 60 T3b) while in 22 patients (10 T3a; 12 T3b) it was extended to the pelvis. Biochemical recurrence was defined using ASTRO definition (three consecutive PSA rises after PSA nadir); no patients underwent control prostate needle biopsy for problems of interpretation related to postactinic tissue changes. All complications were recorded and analyzed using Radiation Morbidity Scoring Criteria (RTOG). RESULTS: At a mean 55-month follow-up, of the 223 patients treated, 26 have escaped controls, 168 are alive (141 disease-free; 27 with recurrent disease) and 29 died; of this group, 11 patients died from clinical progression, while in the others the cause was not related to the prostatic problem; only one patient died from iatrogenic problems. Hormone treatment was conducted in different ways (neoadjuvant, adjuvant, concurrent to radiotherapy or in association) considering patients' characteristics. Most common complications involved rectum and bladder.
 CONCLUSIONS: Radiotherapy is a viable and safe method in the treatment of locally advanced prostate cancer; however, it is essential the role of hormone therapy.

[T&G: an elementary integrated prognostic system for renal carcinoma N0 M0]. / T&G: un sistema prognostico integrato elementare per il carcinoma renale N0 M0.

INTRODUCTION: 25-30% of patients with renal cell carcinoma (RCC) develop metastatic progression during follow up. For this reason many prognostic systems have been developed to try to predict the possibility of recurrence. Unfortunately these systems are often complex in daily use. PATIENT AND METHODS: 1089 were selected from a total of 1985 patients undergoing surgery for renal cell cancer. We have excluded patients with a benign diagnosis, lymph node or distant metastases at diagnosis, with no radical surgery (R1) and those with follow up judged insufficient (<24 months). For each patient a score was defined after evaluating the histological examination of surgical specimens. This score was called T&G and it was equal to the sum of the T pathological (1 for T1, 2 for T2, 3 for T3a, b, c, 4 for T4) and the G according to Fuhrman (1 for G1, 2 for G2, etc.). The range is between 2 and 8. It was then evaluated the disease-free survival according to T & G score to stratify patients into risk classes. RESULTS: During follow-up we had recurrent disease in 246 cases (22.6%; 167 metastases in a single location, 34 local recurrences, 45 metastases) after surgery at a mean distance of 35.6 months (2-205). After comparing each one of the disease free survival curves, we have identified three classes of risk: low risk (T & G 2 and 3), intermediate risk (T & G 4-5), high risk (T & G 6-7-8). We have obtained statistically significant differences between the three classes of risk. The rate of progression was 8.9% for the class of low risk to 48% of the high risk class. The average time (in months) of disease progression decrease from 47 for LR class to 37 for IR up to 29 for a HR Class. DISCUSSION: The T & G score is an extremely basic prognostic system but at the same time it allows an accurate prognostic discrimination in patients with N0 M0 RCC, as demonstrated by the significant differences in the rates and time of progression and disease-free survival.

[Results of targeted therapies for m1 renal cell carcinoma: our experience]. / Risultati della target therapy nel carcinoma renale a cellule chiare m1: la nostra esperienza.

INTRODUCTION: Since a few years ago no effective medical therapies were available to cure metastatic renal cell carcinoma (RCC). Nowadays, encouraging preliminary results support some new therapeutic agents, collectively named as targeted therapies (TT). This paper reviews our experience with the use of TT in the setting of RCC with metastasis at the diagnosis. MATERIAL AND METHODS: Retrospective evaluation of the data of 24 patients (7 females, 17 males, median age: 59aa) affected by clear cell RCC with distant metastatis at diagnosis, treated with TT from 2005 to 2012.20 of the 24 patients (83,3%) underwent preliminary cytoreductive nephrectomy, whereas for the others a percutaneous biopsy of the renal tumor was obtained. 5 (20.8%) patients received an immunotherapy with IL-2 or IFN and then a TT due to a progression. Schedules were applied following heterogeneous regimens along the period of data collection (randomized clinical trial, expanded access, standard indication). Response has been evaluated by RECIST criteria. RESULTS: As first-line therapy of TT 18 patients received Sunitinib, 4 Sorafenib, 2 Temsirolimus; 11 received a second-line (8 Sorafenib, 2 Sunitinib, 1 Everolimus); 6 received also a third-line (5 Everolimus, 1 Tensirolimus). At last available control, after a mean follow up time of 13,7 months (1-29) a progressive disease was present in 12 cases (50%), a stable disease in 6 (25%), a reduction of the disease in 4 (16.5%); 7 patients (29.5%) died; overall mean survival of the entire group was 14,7 months. Even if the study suffers from the limitations related to the small number of cases and the retrospective design, seems that no factors played a role in determining the response to theraphy. CONCLUSIONS: The results of TT in clinical practice resemble the ones from randomised clinical trials. It's extremely hard to predict the response to treatment.

[Ductal carcinoma of the prostate: impact on survival and therapeutic controversies of a rare tumor]. / Carcinoma duttale della prostata: impatto sulla sopravvivenza e controversie terapeutiche di un tumore raro.

Prostate cancer is a disease with a variable clinical course. The possible impact on oncological outcome of non-acinar prostate cancer has not been established yet, especially for ductal adenocarcinoma due to its low frequency, so that its clinical management is not well codified. The disease occurs more often already at an advanced stage of diagnosis, with clinically detectable tumors and advanced pathological stage, partly because of the lack of specific tumor markers, given the poor correlation between PDA and PSA values. In the period between 1997 and 2010 56 patients with PDA on a total of 1265 new diagnoses of cancer were identified, for an overall incidence of 4.5%. 41 patients (75%) had a PDA type II histology, while 15 patients (25%) a PDA type I (pure form). Generally, a surgical treatment was carried out in patients with life expectancy greater than 10/15 years/under 70 years of age, non-metastatic tumors and found to be liable to local resection; radiation therapy was given with 70 Gy in cases with a shorter life expectancy and/or an illness judged unresectable for local extension; hormonal therapy was indicated in all other clinical situations. For all patients, the clinical and pathologic data and follow-ups were re-evaluated. The overall survival and disease-free survival were then analyzed. Given the low incidence of this pathology the relevant literature is poor and therefore the therapeutic approach is not univocal. This paper retrospectively reviews our experience with prostatic ductal adenocarcinoma.

Role of ¹¹C-choline positron emission tomography/computed tomography in evaluating patients affected by prostate cancer with suspected relapse due to prostate-specific antigen elevation.

PURPOSE: The aim of this study was to evaluate the accuracy of (11)C-choline positron emission tomography/computed tomography (PET/CT) in restaging patients affected by prostate cancer and suspected relapse due to prostate-specific antigen (PSA) increase. We also aimed to determine a PSA cutoff that is most suited to the study in terms of best compromise between sensitivity and specificity. Secondary endpoints were a comparison between (11)C-choline PET/CT and histological results, clinical findings, and radiological imaging (CT and magnetic resonance imaging). MATERIALS AND METHODS: We retrospectively evaluated 210 patients (median ± SD age 70 ± 7 years) affected by prostate cancer who underwent (11)C-choline PET/CT. RESULTS: (11)C-choline PET/CT imaging was positive in 116 (55.2%) patients and negative in 94 (44.8%). Receiver operating characteristic (ROC) analysis showed that the highest accuracy (sensitivity 76.8%, specificity 92.5%) for the whole population was achieved when the PSA level of 1.26 ng/ml level was used as the cutoff value for interpreting the results (P = 0.0001 and the area under the ROC curve AUC 0.897). For patients treated with surgery or surgery plus radiotherapy the cutoff was 0.81 ng/ml (sensitivity 73.2%, specificity 86.1%). For patients treated with radiotherapy alone, the cutoff was 2.0 ng/ml (sensitivity 81.8%, specificity 92.9%). CONCLUSION: Our results indicate that (11)C-choline PET/CT is a useful diagnostic tool in patients affected by prostate cancer and a relapsed PSA level. The highest accuracy for all patients is obtained with a PSA cutoff level of 1.26 ng/ml, above which the imaging study is performed (0.81 ng/ml for patients treated with surgery or surgery plus radiotherapy and 2.0 ng/ml for patients treated with radiotherapy alone).

Simple enucleation is equivalent to traditional partial nephrectomy for renal cell carcinoma: results of a nonrandomized, retrospective, comparative study.

PURPOSE: The excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation. MATERIALS AND METHODS: We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival. RESULTS: Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 ± 37.8 and 54.4 ± 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates. CONCLUSIONS: To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

Validation of the 2009 TNM version in a large multi-institutional cohort of patients treated for renal cell carcinoma: are further improvements needed?

BACKGROUND: A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b (< or =10 cm vs >10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers. OBJECTIVE: Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer. DESIGN, SETTING, AND PARTICIPANTS: Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers. INTERVENTION: Patients underwent either radical or partial nephrectomy. MEASUREMENTS: Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery. RESULTS AND LIMITATIONS: In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend <0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages. CONCLUSIONS: The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version.

[Diagnostic and therapeutic approach in patients with urinary calculi]. / Percorso diagnostico-terapeutico per il paziente con calcolosi urinaria.

The natural history of urolithiasis includes the risk of recurrence and of the development of chronic kidney and/or bone disease, which is why a thorough clinical and metabolic evaluation of these patients is of the utmost importance at disease onset. This paper is aimed at identifying the type of urolithiasis, the related risk factors, and the corresponding treatment options. The diagnostic and therapeutic approach described here includes 1) accurate history taking to detect secondary nephrolithiasis and screen for the main risk factors for kidney and bone disease; 2) metabolic evaluation graded according to different complexity levels based on the severity of the disease and the presence of risk factors; 3) carrying out appropriate imaging procedures. The resulting information allows to plan treatment based either on general rules of lifestyle and diet, or on selected medical intervention, if necessary. This report, which is based on current guidelines, was produced by the Gruppo Italiano di Studio Multidisciplinare per la Calcolosi Renale. It is addressed to all professionals involved in the management of patients suffering from nephrolithiasis, first of all general practitioners, who often become involved immediately at the onset of the disease.

Immunohistochemical detection and localization of somatostatin receptor subtypes in prostate tissue from patients with bladder outlet obstruction.

BACKGROUND AND AIM OF THE STUDY: Scant information on the cellular distribution of the five somatostatin receptor (SSTR) subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate. MATERIALS: The study was conducted in 14 surgical specimens of normal prostate tissue from adenomectomy specimens from patients with bladder outlet obstruction. The distribution and localization of the 5 somatostatin receptor (SSTR) subtypes was investigated with an immunohistochemical technique. Specificity of the antibodies against the 5 receptor subtypes was preliminarily investigated. RESULTS: Close to 90% of secretory cells showed a weak positivity in the cytoplasm, the proportion ranging from 86.3% (SSTR4) to 89.9% (SSTR5). Strong immunoreactivity was seen in a small proportion of cells, ranging from 0.8% (SSTR3) to 3.2% (SSTR1). For the subtypes 1 and 3 the greatest proportion of basal cells showed a moderate intensity (42.5 and 41.4%, respectively), strong immunoreactivity being observed only in 18.1 and 15.8% of cells, respectively. For the subtypes 2, 4 and 5, the majority of cells showed a weak intensity (72.3, 65.7 and 65.1%, respectively). Subtype 1 showed a strong immunoreactivity in the cytoplasm in 60% of the smooth muscle cells. With subtypes 2, 3 and 4 the greatest proportion of cells showed a weak intensity (63.4, 89.8 and 81.7%, respectively). With the subtype 5 the majority of cells (59.8%) were negative. Subtype 1 showed a strong immunoreactivity in the cytoplasm in 98.6% of the endothelial cells. With subtypes 3 and 4 the greatest proportion of cells showed a weak intensity (73.5 and 56.4%, respectively). With the subtype 2 and 5 the majority of cells were negative (59.1 and 50.7%, respectively).

Fistulas between lower urinary tract and bowel: our experience in 15 years.

OBJECT: Fistulas between bowel and low urinary tract are not frequent and could be due to different causes. Diagnosis and treatment need a particular care to assure to patient a good result. Authors report their last 15-years experience. MATERIALS AND METHODS: From 1990 and 2005 22 patients have been quite carefully investigated and surgically treated; 17 men and 5 women of age between 39 and 81 years old. In particular 2 vesico-ileal fistulas, 12 colo-vesical have been treated: in all these situations we proceed by intestinal resection and fistulas repairing at the same time. Three rectovesical and 3 recto-urethral fistulas have been treated by fistula's way removal (with different approaches) and in a case by preparing a definitive urinary derivation. Finally, 2 complex fistulas have been treated by preparing a definitive urinary derivation. RESULTS: The typical symptoms presence must be carefully researched because it could be useful in diagnosis; radiological and endoscopic procedures could be useful for treatment planning, also if they have a quite low sensibility. In 20 cases, the treatment has achieved a good and lasting result. In 1 case we had a relapse, in another one patient died for sepsis. CONCLUSION: Diagnosis of fistulas has to be quite careful and it is necessary to plan the treatment, that is always surgical, also considering that sometimes it's leading to serious complications.

Surgical approach to urinary endometriosis: experience on 28 cases.

OBJECTIVES: Endometriosis (e.) involving the urinary tract must be regarded as a rare condition with specific surgical implications. Our experience on the treatment of 28 patients is presented. PATIENTS AND METHODS: Twenty-eight patients with a urological e. (bladder 11 patients, ureter 14, both bladder and ureter 3) were observed and treated between 1995 and 2005. Thirteen patients (46%) had been previously surgically treated for pelvic e. at a mean distance of 22 months before. All the patients with bladder e. presented with typical symptoms related to menses and the urinary location was isolated in 42.8%. Differently, the patients having ureteral involvement complained often a vague or silent symptomatology, but they always showed some extra-urinary pelvic locations. Among the cases with bladder e., 2 patients underwent TUR and hormonal therapy and 12 partial cystectomy. The patients with ureteral e. were submitted to ureterolysis in 5 cases, segmentary ureterectomy and uretero-ureteroanastomosis in 2 and terminal ureterectomy and ureterocystoneostomy in 8. Two more cases with ureteral e. were nephrectomized due to end-stage renal atrophy. RESULTS: At a mean distance of 58 months (9-110 months) from surgery, 22 patients have a unremarkable follow-up. On the other hand, an urological relapse was evidenced in 5 cases previously submitted to TUR (2 cases), ureterolysis (2 cases) or segmentary ureterectomy and termino-terminal ureteral anastomosis (1 case). The relapsing e. was treated by partial cystectomy or terminal ureterectomy with ureterocystoneostomy, with good results over time. CONCLUSION: Urinary tract is rarely involved by e., but this condition has peculiar clinical and surgical implications. Being TUR ineffective, the therapy of choice of bladder e. is partial cystectomy, possibly via a laparoscopic approach. Differently from bladder e., the preoperative diagnosis of ureteral e. is surely hard. So, a high index of suspect should be regarded in each young female patient with a ureteral stricture and a study of the upper urinary tract (US and/or urography) should be performed in all the patients with pelvic e. Ureterolysis can be successful only in a minority of the cases showing a very limited disease not determining any urinary flow obstructions. In all the other cases the procedure of choice is terminal ureterectomy and ureterocystoneostomy without employing the distal ureter.

Surgical treatment of adrenal metastasis from renal cell carcinoma: a single-centre experience of 45 patients.

OBJECTIVE: To report, in a retrospective study, the diagnostic problems and oncological results of surgery in patients with either synchronous or metachronous adrenal metastasis, which are uncommon in renal cancer, at 2-10% of patients. PATIENTS AND METHODS: Of 1179 patients treated for renal cancer between 1987 and 2003, 914 had renal surgery with concomitant ipsilateral adrenalectomy (routinely in 875 and for abnormal findings on computed tomography, CT, in 39) and 15 contralateral adrenalectomy (all after suspicious findings on CT). During the follow-up after renal surgery, another 14 patients had adrenalectomy for CT evidence of an abnormal adrenal gland, contralateral to the previous renal tumour in 12 and bilaterally in two. RESULTS: Of 914 ipsilateral adrenal glands removed during renal surgery, 854 (93.5%) were normal on pathological examination, 28 (3%) had a benign pathology, six (0.8%) were directly infiltrated by the tumour and 26 (2.7%) were metastatic. For both benign and metastatic ipsilateral adrenal pathology, CT had sensitivity, specificity and positive/negative predictive values of 47%, 99%, 73% and 96%, respectively. Of 29 contralateral glands removed because of suspicious CT findings (15 at diagnosis of renal cancer, 14 during the follow-up) there was no abnormality in one (3.4%), a benign pathology in seven (24%) and a metastasis in 21 (72%). Thus there were 32 synchronous (incidence 2.7%; ipsilateral to the renal tumour in 24, contralateral in six and bilateral in two), and 13 metachronous adrenal metastases (incidence 1.0%; contralateral in 11 and bilateral in two). The metachronous metastases were diagnosed at a mean (range) interval of 30.6 (8-73) months after renal surgery. No ipsilateral adrenal metastases were discovered at diagnosis or during the follow-up in the 382 patients with an organ-confined renal tumour of <4 cm in diameter. Twenty-seven patients with an isolated adrenal metastasis (synchronous in 14, metachronous in 13) had statistically significantly (P < 0.001) better survival than the 18 (all synchronous) with multiple sites of metastatic disease. In particular, there was long-term survival (mean 83 months) in 10 patients with an isolated adrenal metastasis. CONCLUSION: Sparing the ipsilateral adrenal is advisable only for organ-confined renal tumours of <4 cm in diameter; clinical local staging of renal cancer is the best predictor of the risk of adrenal metastasis. Conversely, CT had good diagnostic ability for the contralateral adrenal gland, especially during the follow-up. Some patients with isolated adrenal metastasis could be treated by metastasectomy, with long-term survival free of disease and confirming that, even if in a few and unselectable patients, removing all the neoplastic bulk can be curative. Nevertheless, the high rate of relapse underlines the need for an effective systemic therapy, and more so for widespread metastatic disease that currently cannot be cured.