Early diagnosis of bladder cancer through the detection of urinary tyrosine-phosphorylated proteins.

BACKGROUND: A noninvasive, highly sensitive and specific urine test is needed for bladder cancer (BC) diagnosis and surveillance in addition to the invasive cystoscopy. We previously described the diagnostic effectiveness of urinary tyrosine-phosphorylated proteins (UPY) and a new assay (UPY-A) for their measurement in a pilot study. The aim of this work was to evaluate the performances of the UPY-A using an independent cohort of 262 subjects. METHODS: Urinary tyrosine-phosphorylated proteins were measured by UPY-A test. The area under ROC curve, cutoff, sensitivity, specificity and predictive values of UPY-A were determined. The association of UPY levels with tumour staging, grading, recurrence and progression risk was analysed by Kruskal-Wallis and Wilcoxon's test. To test the probability to be a case if positive at the UPY-A, a logistic test adjusted for possible confounding factor was used. RESULTS: Results showed a significant difference of UPY levels between patients with BC vs healthy controls. For the best cutoff value, 261.26 Standard Units (SU), the sensitivity of the assay was 80.43% and the specificity was 78.82%. A statistically significant difference was found in the levels of UPY at different BC stages and grades between Ta and T1 and with different risk of recurrence and progression. A statistically significant increased risk for BC at UPY-A ⩾261.26 SU was observed. CONCLUSIONS: The present study supplies important information on the diagnostic characteristics of UPY-A revealing remarkable performances for early stages and allowing its potential use for different applications encompassing the screening of high-risk subjects, primary diagnosis and posttreatment surveillance.

Denial and oncological pathology: Case report of a massive testicular cancer.

LITERATURE: The cancer of testicles represents 1% of male neoplasms and 5% of urological malignant neoplasm. Its incidence has been growing in Western societies. Cancer of testicles usually presents as an increase of consistence in one testicles and absence of pain, as a casual ultrasound scan finding, or it could be highlighted by a scrotal injury. The surgical treatment is either radical orchiectomy or radical orchiectomy plus retroperitoneal lymph node dissection. CASE PRESENTATION: The case presented concerns a 48-year-old male with a history of left testicular trauma and subsequent hypotrophy. Over the next 4 years, the patient developed a testicle size increase up to 15 cm in diameter. At diagnosis, he had retroperitoneal lymphadenopathy. The patient was, after surgery, referred to the oncology department. CONCLUSION: The awareness of the male population respect to testicular cancer and its screening methods (e.g. self-examination) is essential to make the diagnosis at an early stage. It is also essential to psychologically support patients undergoing surgical and/or pharmacological therapy due to risk of determining anxiety or depression compared to the whole population.

Proposal of an improved prognostic classification for pT3 renal cell carcinoma.

PURPOSE: The prognostic accuracy of the current TNM 2002 staging system for locally advanced renal cell carcinoma has been questioned. To contribute to the development of a more accurate classification for this stage of disease we assessed the correlation between patterns of invasion in the pT3 category and outcomes in a large multi-institutional series. MATERIALS AND METHODS: Pathological data and clinical followup on 513 pT3 renal cell carcinoma cases treated with radical nephrectomy between 1983 and 2005 at 3 Italian academic centers were retrospectively reviewed. Cause specific survival rates were calculated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Estimated overall 5-year cause specific survival was 50.1% at a median followup of 61.5 months in survivors. The current TNM classification was not a significant outcome prognosticator. Patients with a tumor invading only the perirenal or sinus fat were at lowest risk for death from the disease. Patients at intermediate risk had tumors with invasion of the venous system alone. Simultaneous perirenal fat and sinus fat invasion or perirenal fat and vascular invasion as well as adrenal gland involvement characterized high risk tumors. Low risk tumors could be further divided into 2 groups with different outcomes based on a size cutoff of 7 cm. Our classification was a significant predictor of survival on multivariate analysis as well as M stage, N stage, Fuhrman grade and tumor size. CONCLUSIONS: We confirm that the prognostic usefulness of the current 2002 TNM system for pT3 renal cell carcinoma is limited. We have identified 4 groups of tumors with distinct patterns of invasion and significantly different survival probabilities in this category. Large prospective series are needed to validate these findings.

Transobturator tape in the management of female stress incontinence: clinical outcomes at medium term follow-up.

OBJECTIVE: To assess the efficacy of transobturator tape (TOT) in the management of stress urinary incontinence at a medium term follow-up. METHODS: TOT is a polypropylene tape positioned through the obturator foramen. 70 patients with type II urinary stress incontinence were treated with TOT between June 2003 and May 2006. Patients were prospectively studied by physical examination, quality of life questionnaire (I-QOL), visual analog scale, global impression (dry, improved, same, worse), preoperative urodynamic study, and pre- and postoperative flowmetry. Statistical analysis (t test) of the difference in I-QOL scores and flowmetry was made by StatSoft V. 5.1. RESULTS: The average follow-up was 32 (range 12-48) months. The I-QOL score increased statistically significantly by 40 points. The average percent improvement was 80%. 90% (63/70) of the patients were dry and 5% (4/70) were improved. The pre- and postoperative uroflowmetry studies were not statistically different. Vaginal erosion occurred in 4 patients. CONCLUSION: TOT is a safe procedure with a good efficacy at 32-month follow-up.

Actual experience and future development of gemcitabine in superficial bladder cancer.

Gemcitabine has a molecular weight of 299 D, lower than that of commonly-used intravesical chemotherapeutic agents such as mitomycin C (389 D) and doxorubicin (589 D). This may enable gemcitabine to penetrate the bladder mucosa with beneficial effects in the treatment of early invasive bladder cancer (T1 disease). At the same time the molecular weight is high enough to prevent significant systemic absorption in an intact bladder. Based on the results of phase I studies, it appears that the 2000 mg dose of gemcitabine in 50/100 ml normal saline when administered intravesically for up to 2 h once a week for 6 weeks has unremarkable systemic and local side effects and therefore should be considered the most convenient schedule. The currently available phase II studies have assessed the activity of intravesical gemcitabine on a marker lesion in intermediate risk superficial bladder cancers (SBC), showing complete responses in up to 56% of cases. Few attempts have been made to test the activity of intravesical gemcitabine in high risk SBC achieving unexpected complete responses in BCG refractory CIS. Gemcitabine seems to have fulfilled the requirements to be a promising new candidate for standard intravesical therapy in SBC so far. Further phase II trials exploring the activity of gemcitabine on highly-recurrent intermediate risk or high risk SBC would provide additional information to foresee its efficacy in clinical practice and thus constitute the framework for large comparative phase III trials.

Clinical efficacy of Apomorphine SL in erectile dysfunction of diabetic men.

Although subgroup analyses from large randomised premarketing studies have shown that Apomorphine SL enhances the percentage of erections firm enough for sexual intercourse in diabetic men, the clinical role of the drug in this patient population remains to be elucidated. The aim of the present study was to assess the efficacy of Apomorphine SL in diabetic males with erectile dysfunction (ED) and to identify factors predicting those who may benefit from the treatment. A total of 130 diabetic patients were randomised to receive either four tablets of 3 mg Apomorphine or a matching placebo. Assessments of efficacy comprised the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and the one-item global efficacy question (GEQ). Patients with both a positive response to the GEQ and an improvement of at least 5 points in the EF domain of the IIEF were considered responders and subanalysed by several parameters indicative of the severity of both ED and diabetes. Response rate was 17% after placebo and 22% after Apomorphine SL. The EF domain of the IIEF and both questions 3 and 4 scores did not significantly improve in either of the two arms over the baseline. A younger age and a lower Hb1Ac were significantly linked to the status of responder in the Apomorphine arm. Apomorphine SL failed to show a statistically significant benefit over a placebo, but 22% of patients had a clinically significant erectile response. These figures seem to suggest that the drug has a limited use for ED diabetic patients.

The importance of psychosexual counselling in the re-establishment of organic and erotic functions after penile prosthesis implantation.

Although many studies about penile prosthesis implantation (PPI) have been published so far, only a small amount of them take into account patients and partners outcome in terms of satisfaction and erotic function. The aim of this study is to explore the value of psycosexual counselling in and the sexual and erotic function of penile prosthesis recipients. Thirty patients and their partners were randomised into two groups. In arm A (case group) patients and their partners underwent a multistep psychosexual counselling before and after surgery. In arm B (control group) surgery was performed without the specific psychosexual counselling scheme. Specific questionnaires (International Index of Erectile Function (IIEF) and the Sexual Daydreaming Scale (SDS)) were administered before surgery and 12 months afterwards. Twenty-four months postoperatively patients were asked to complete the Global Assessment Questions (GAQ) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), while their partners were asked to answer to the EDITS partner's section. Between January 2009 and October 2011, we enrolled 30 patients undergoing PPI in our institution (15 in each arm). Twenty-four months postoperative follow-up is available for all of them. No significant differences between the two groups in terms of baseline questionnaires scores were observed. Mean IIEF score was significantly higher in case group (arm A 68.3, arm B 53.4, P-value<0.001). At 12 months after PPI the improvement of erotic function according to SDS was significantly higher in the study group for both patients and their partners. Improvement in satisfaction rates were confirmed at 24 months, with statistically significant scores for EDITS in arm A patients and partners as compared with arm B. PPI with a pre- and postoperative psychosexual counselling scheme resulted in better postoperative sexual activity and erotic function for both patients and partners than PPI alone.

Bladder cancer and cigarette smoking in males: a case-control study.

Cigarette consumption was compared between 355 males with cancer of the lower urinary tract and 276 male hospital controls. Both duration of smoking and average daily consumption of cigarettes showed a dose-response relationship with risks of developing bladder cancer. Quitting smoking seems to have a protective role, whereas higher relative risks are associated with an early age at start of smoking. The use of a filter seems to have a weak protective effect.

Recent applications of the sentinel lymph node concept: preliminary experience in prostate cancer.

AIMS AND BACKGROUND: Following the widespread use of radioguided surgery (RGS) in melanoma and breast cancer, we applied this new surgical strategy to prostate cancer (PC). The aims of this study were 1) to evaluate the accuracy of RGS in the detection of prostatic sentinel lymph nodes (SLN), and 2) to verify if pelvic lymphadenectomy (LAD) is an accurate means to detect solitary micrometastases. STUDY DESIGN: We investigated 48 patients with PC confirmed by transrectal biopsy who underwent radical prostatectomy and bilateral LAD. A dose of 99mTc-labeled nanocolloid particles was injected into the prostate after needle positioning by ultrasonography. Serial imaging was obtained with a gamma camera, identifying 1) the first radioactive lymph node (sentinel lymph node, SLN); 2) other radioactive lymph nodes, and 3) non-active lymph nodes. RESULTS: Forty-three SLNs were identified in 48 patients. Twenty SLNs were located at unusual sites with respect to the extent of conventional LAD. Five SLNs were positive for micrometastases and two of these were located outside the usual LAD area. No micrometastases were found in any of the remaining lymph nodes (active and non-active). CONCLUSIONS: These preliminary results are in agreement with the few previous scientific contributions available on this topic and indicate that it is possible to reduce the extent and duration of surgery and necessary to reevaluate the conventional sites of lymphatic drainage.

[Bladder leiomyoma. Presentation of a case]. / Il leiomioma vescicale. Presentazione di un caso.

After a brief review of the literature a case of leiomyoma of the bladder accidentally identified during endoscopy for prostatic adenomatosis is presented.

[Diet therapy in the prevention of renal calculosis]. / La terapia dietetica nella profilassi della calcolosi renale.

The importance of diet within the framework of effective therapeutic measures in the prophylaxis of recurring lithiasis is emphasised. Some diet sheets are presented.

[Voiding ultrasonographic cystourethrography]. / L'ecocistouretrografia perminzionale.

Transvaginal ultrasonography examines the bladder base, the urethral anatomy and the relationship between these structures. This procedure particularly evaluates the striated sphincter and periutrehral structures, during micturition attention is focused on elasticity of urethral walls, deviation of urethral axis, the presence of fibrotic rings, fibrosis extending to the whole urethra and on urethral diverticuli. At che present, the literature available does not provide certain diagnostical criteria for the identification of female vaiding disorders. The high number of proposed therapeutical solutions indicate that the solution to this problem is yet to be found.

[Does PSA density of the transition zone represent a useful parameter in the diagnosis of prostate carcinoma?]. / PSA density della zona di transizione rappresenta un parametro utile nella diagnostica del carcinoma prostatico?

Prostate specific antigen (PSA) has unequivocally proved its clinical usefulness ad a serum marker for prostate cancer. In order to enhance the specificity of serum PSA, several diagnostic parameters have been employed including PSA density of transition zone (TZ). The authors report their experience on the efficacy of PSA density TZ with level of PSA < 4 ng/ml, between 4-10 ng/ml, > 10 ng/ml, in the diagnostic of prostate cancer. The PSA density of TZ resulted uscless for PSA levels < 4 ng/ml, but improved the diagnostic specificity associated to PSA serum in the PSA levels ranging between 4-10 ng/ml and > 10 ng/ml.

[Radical prostatectomy: comparison of technics]. / Prostatectomia radicale: tecniche a confronto.

From 1989 until today 46 patients aged 44-75 years underwent a radical prostatectomy two of whom transperineal and another 44 patients underwent a retropubical prostatectomy (twenty of whom with the nerve sparing technique). Based on our experience, the clinical stages that benefit from a radical prostatectomy as are as followed: T1b, T1c, T2a, T2b; T2c, in patients who present a good A.S.A., a remaining life-span of ten years is expected. Our preference, regarding the best access was clearly the traditional retropubical which allowed us on a preliminary bases a bilateral iliaco-otturatorial lymphoadenectomy with extemporaneus histological exams. Based on our experience we do not see an indication for a radical surgical intervention in the following with: P.S.A. higher than 60 ng./ml in patients with a clinical stage C. Positive abdominal-pelvical computer tomography for macrometastical lymph nodes. Positive bone scintigraphy. Patients over the age of 75 years.

[Preoperative subcutaneous immunotherapy with interleukin-2 in renal carcinoma with synchronous metastasis: randomized clinico-biological study. Preoperative use of Il-2 in renal carcinoma]. / Immunoterapia sottocutanea preoperatoria con interleuchina-2 nel carcinoma renale con più sedi metastatiche sincrone: studio randomizzato clinico-biologico. IL-2 preoperatoria nel carcinoma renale.

Despite the efficacy of IL-2 in the treatment of metastatic renal cell carcinoma (RCC), the prognosis of patients with synchronous metastases still remains poor. Nephrectomy itself, as well as other surgical operations, may further suppress the antitumor immune response. Previous studies suggested that the preoperative injection of IL-2 may neutralize surgery-induced lymphocytopenia in advanced colon cancer. On this basis, a pilot randomized study was performed in an attempt to evaluate the effects of a preoperative administration of IL-2 on postoperative lymphocyte numbers and on the survival in advanced RVV patients with more than 3 synchronous metastases. The study included 20 consecutive patients, who were randomized to receive nephrectomy alone or nephrectomy plus preoperative subcutaneous immunotherapy with IL-2 (18 million IU/day for 3 days). Then, all patients underwent postoperative immunotherapy with IL-2 (6 million IU/day for 5 days/week for 6 weeks). Surgery-induced lymphocytopenia was completely abolished by IL-2 preoperative injection. The frequency of postoperative complications was significantly higher in controls than in patients preoperatively treated with IL-2. On the contrary, significant differences between control and patients preoperatively treated with IL-2 were observed neither in the clinical response to IL-2 immunotherapy, nor in the percent of 1-year survival. The results of this preliminary pilot study would suggest that IL-2 preoperative immunotherapy may neutralize surgery-induced lymphocytopenia and reduce the postoperative complications in RCC patients with synchronous metastases, without, however, influencing their prognosis in terms of survival time.

[Orthotopic ileal neobladders in men and women: techniques and comparison]. / Le neovesciche ileali ortotopiche nell'uomo e nella donna: tecniche a confronto.

PURPOSE: evaluation of results and complications of ileal orthotopic neobladders in men and women with transitional cell carcinoma. MATERIALS AND METHODS: between 12-89 and 12-95 we performed 146 radical cystectomy for bladder neoplasm, in 32 patients we can perform ileal orthotopic neobladder, 29 were male and 3 were female. Oncologic indications to this kind of operation were: clinical stage T2, T3a, T3b, T1G3 multicentric and or recurrence, absence of metastasis absence of nodal metastasis, negativity of urethral biopsy. General contraindications were urethral stenosis and incontinence. Oncological contraindications, in woman, were bladder neck neoplasm or urethral neoplasm. In 4 patients we use Camey II technique, in 19 pts we performed the paduan ileal neobladder, in 9 pts we use Hautmann technique. 7 patients performed neoadjuvant chemotherapy with 4 circles of MVAC, 4 pts underwent adjuvant chemotherapy, and 2 pts salvage chemotherapy. In woman we take care during cystectomy to dissect cardinal ligament very close to cervix uteri, to resect the uterosacral ligament far to the sacrum. We did not dissect under the ureter and we cut the urethra 0.5-1 cm far from the bladder neck. RESULTS: follow up was between 6 and 66 months. 24 patients are now alive and disease free, 2 patients are alive with disease progression, 1 have a pelvic recurrence and 1 have pulmonary recurrence. 4 pts died for disease progression and 2 for non oncological cause, quality of life was considered as regard to continence and sexual activity. 1 pts was completely incontinent and 1 pts has nocturnal incontinence with a daily micturation every 1 hour. We can evaluate only 18 patients for sexual activity and 4 reported normal erection. COMPLICATIONS: in three cases we had to reoperate for early complications due to mechanical bowel obstruction, ileocutaneous fistula and wound dehiscence. In three cases we had the formation of stones, in two patients ureteroileal stenosis, in two cases urethro-ileal stenosis and 1 reflux from the neobladder. Orthotopic ileal neobladder allows a very good quality of life and is the first choice derivation after radical cystectomy.

[Clinical response and survival in metastatic renal carcinoma during subcutaneous administration of interleukin-2 alone. Subcutaneous Il-2 in renal carcinoma]. / Risposta clinica e sopravvivenza nel carcinoma renale metastatico durante somministrazione sottocutanea di sola interleuchina-2. Il-2 sottocutanea nel carcinoma renale.

Several clinical studies have demonstrated the efficacy of subcutaneous immunotherapy with Il-2 alone in metastatic renal cell carcinoma (RCC). In an attempt to better define the clinical parameters which may predict the efficacy of treatment, the present study shows the results obtained with subcutaneous Il-2 alone in 91 evaluable metastatic RCC patients. IL-2 was injected subcutaneously at 3 million IU twice/day for 5 days/week for 6 weeks, corresponding to one immunotherapeutic cycle. In nonprogressing patients, a second cycle was given after 28-day rest period. A complete response (CR) was achieved in 2/91 patients. Moreover, 19/91 patients had a partial response (PR). Therefore, objective response (OR) rate was 21/91 (23%) patients. Stable disease (SD) was achieved in 41 patients, while the remaining 29 patients had a progressive disease (PD). OR rate was significantly higher in patients with a long disease-free survival than in patients with synchronous metastases, in nephrectomized patients than in the non-nephrectomized ones, and in patients with high than in those with low PS. The survival obtained in patients with CR or PA was significantly longer with respect to that found in patients with SD or PD. The toxicity was substantially low in all patients. This study confirms that the subcutaneous immunotherapy with IL-2 alone is an effective and well tolerated therapy of metastatic RCC.

Analysis of radical cystectomy and urinary diversion complications with the Clavien classification system in an Italian real life cohort.

INTRODUCTION: Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. MATERIALS AND METHODS: A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. RESULTS AND LIMITATIONS: 467 patients were enrolled. Median age was 70 years (range 35-89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type ≥IIIa (p = 0.03). A longer operative time was an independent risk factor of CCS ≥III (OR: 1.005; CI: 1.002-1.007 per minute; p = 0.0001). CONCLUSIONS: In our study, RC is associated with a significant morbidity (65%) and a reduced mortality (1.7%) when compared to previous experiences. The modified CCS represents an easily applicable tool to classify the complications of RC and UD in a more objective and detailed way.

[Batson's paravertebral venous plexus and single vertebral metastases from renal cell carcinoma]. / Circolo venoso paravertebrale di Batson e metastasivertebrali singole da carcinoma renale.

OBJECTIVES: The presence of a single site bone metastasis in patients with renal cell carcinoma (RCC) is a rare clinical event. We report a single case of RCC with solitary vertebral metastasis and review of literature about renal tumor spreading in order to understand the anatomic explanation for this peculiar clinical case. METHODS: We have considered the single case and reviewed current and past literature to describe the anatomic and functional background of this clinical situation. RESULTS: There are rare cases of single vertebral metastasis from RCC and these are characterized from a contemporary neoplastic thrombus. The neoplastic thrombus could justify the tumoral back-flow into the paravertebral anasthomoses and so into vertebral venous sinusoids. The rich anasthomotic system that surrounds kidneys and the experimental evidence of anasthomotic links among perirenal Lejars venous system and paravertebral Batson's venous system could explain these clinical evidences. CONCLUSION: Enrolment of para-vertebral Batson's venous system could have a major role in the RCC vertebral metastatic diffusion.

[The role of non-invasive urodynamics in bladder outlet obstruction diagnosis in male patients]. / Il ruolo dell'urodinamica non-invasiva nella diagnosidell'ostruzione cervico-uretrale nell'uomo.

PURPOSE: Many methods have been suggested to assess bladder outlet obstruction, as defined by the gold standard of pressure flow studies. A comprehensive review of the literature on the different methods used to diagnose bladder outlet obstruction by non-invasive means was performed in order to compare those methods to invasive urodynamics in terms of sensitivity and specificity. MATERIALS AND METHODS: A MEDLINE search was done of the published literature covering from December 2003 on non-invasive methods, including only single measures to diagnose bladder outlet obstruction. We performed a comparison between all methods in terms of sensitivity and specificity for each test. For many techniques these values were calculated directly from the data presented in the article. RESULTS: There has been applied many methods to diagnose bladder outlet obstruction. Those methods were divided into uroflowmetry, condom-catheter method, penile cuff method and Doppler ultrasonography urodynamics. Each method has been described and discussed in terms of its role in adding information to the diagnostic work-up for bladder outlet obstruction. CONCLUSIONS: Pressure flow studies still remain the gold standard for assessing bladder outlet obstruction. However non-invasive urodynamics is a promising branch. Probably the most reliable information is given by the association of numerous methods together.