Correlation between Voltammetry of Immobilized Particles and Mott-Schottky analysis of metal corrosion patinas.

The conjoint application of the voltammetry of immobilized particles (VIMP) methodology and the Mott-Schottky analysis (MS) of impedance data to studying metal corrosion patinas is described. The study is applied to copper and bronze objects exploiting the semiconducting character of cuprite and other copper corrosion products. A simplified theoretical modeling of MS analysis at microparticulate deposits extracted from metal corrosion layers attached to graphite electrodes is provided. The proposed model compensates for the disturbing effect of the regions of the basal electrode directly exposed to the electrolyte. Alternative models accounting for the variation of the density of charge carriers with depth are tested as well as the correlation between VIMP and MS data with reasonably satisfactory results.

Endoscopic stapedotomy: safety and audiological results in 150 patients.

OBJECTIVE: The most widely accepted treatment for otosclerosis is currently microscopic stapes surgery under either local or general anesthesia. The aim of the study is to describe the surgical steps in endoscopic stapes surgery and to evaluate the audiologic and surgical outcomes. MATERIALS AND METHODS: All patients who underwent exclusive endoscopic stapes surgery or revision surgery for previous stapedotomy between November 2014 and September 2018 were enrolled in this study. Demographic data, surgical information, preoperative and postoperative pure tone averages and air bone gaps, intraoperative and postoperative complications and follow-up data were summarized and gathered in a database for further consideration and analysis. RESULTS: In the period examined, 181 stapes surgical procedures were performed and out of these 150 met the inclusion criteria. There were no cases of major intraoperative complications. Sensorineural hearing loss was observed in one case. In one patient a gusher effect occurred during surgery. The postoperative air-bone gap improved significantly compared to the preoperative gap (8 vs 29 dB HL, respectively), and the mean air-bone gap closure was 20 dB HL. In 78.7% of cases, the observed postoperative air-bone gap was less than 10 dB HL and in 14% it was between 11 dB HL and 20 dB HL. An ABG closure lower than 20 dB HL was achieved in a total of 92.7% of patients. CONCLUSIONS: Endoscopic stapes surgery is a safe procedure with a low risk of peri- or postoperative complications and is a possible alternative to the traditional microscopic surgical procedure in the treatment of otosclerosis.

Update on histopathological evaluation of lymphadenectomy specimens from prostate cancer patients.

BACKGROUND: Metastases to lymph nodes (LNs) represent an unfavorable prognostic factor in patients with prostate cancer (PCa). Histological examination represents the gold standard in the evaluation of the lymphadenectomy (LND) specimens for the presence of secondary deposits. METHODS AND RESULTS: The metastatic detection rate can vary according to the approach adopted in the microscopic analysis of the LNs, which includes frozen-section examination, total inclusion of the tissue with and without whole-mount sections, serial sectioning, and the application of immunohistochemistry. The assessment of the sentinel LN, the search for micrometastases, and the evaluation of atypical LN metastatic sites further contribute to the detection of the metastatic spread. CONCLUSION: In this review, an update on the histopathological evaluation of LND specimens in patients with PCa is given, and focus is made on their clinical and prognostic significance.

Safety and efficacy of percutaneous nephrolithotomy in the Galdakao - Modified Supine Valdivia position: A prospective analysis.

OBJECTIVE: Aim of the present study was to evaluate the safety and efficacy of Percutaneous Nephrolithotomy (PCNL) in the Galdakao- Modified Supine Valdivia (GMSV) position in order to predict operative time, stone-free rate and onset of complications taking into account comorbidity, stone-related parameters and anatomic upper urinary tract abnormalities. MATERIAL AND METHODS: A prospective evaluation of patients who underwent to PCNL in GMSV position for renal stones > 2 cm, from January 2009 to February 2015 was performed. According to the technique, upper urinary tract abnormalities, stone chemical and morphological characteristics, and patients' history were matched with operative outcome, in terms of stone-free, intervention time and incidence of perioperative complications. RESULTS: Seventy-two cases were collected; mean operative time was 105 minutes (DS 41): staghorn stones and the presence of comorbidity resulted statistically significant variables. The complication-rate resulted in line with data showed in literature: hyperpyrexia and hemorrhage were the more frequently complications found. The overall stone-free was reached in 48 patients (67%), and it was influenced by patients' anatomic abnormalities. CONCLUSIONS: In the treatment of renal stones, PCNL may be a safe and effective choice; nevertheless, patients' anatomic abnormalities or staghorn-stones may influence the outcomes. Thus, a prospective study with a larger population is needed to verify our outcomes.

Neuroendocrine differentiation in prostate cancer: novel morphological insights and future therapeutic perspectives.

Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer (CRPC) The detection of NEPC has clinical implications as these patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. The poor molecular characterization of NEPC accounts in part for the lack of disease specific therapeutics. Several mechanisms are involved in NE differentiation, including inflammation and autophagy, and may actually represent future therapeutic targets for advanced NEPC patients. Furthermore, a growing body of evidence suggests a potential role of circulating tumor cells in the early diagnosis and treatment of NEPC. Here we summarize the recent findings on NEPC pathogenesis and we discuss the ongoing clinical trials and future perspectives for the treatment of NEPC patients.

Emerging strategies to overcome the resistance to current mTOR inhibitors in renal cell carcinoma.

The mammalian target of rapamycin (mTOR) has emerged as an attractive cancer therapeutic target. Treatment of metastatic renal cell carcinoma (mRCC) has improved significantly with the advent of agents targeting the mTOR pathway, such as temsirolimus and everolimus. Unfortunately, a number of potential mechanisms that may lead to resistance to mTOR inhibitors have been proposed. In this paper, we discuss the mechanisms underlying resistance to mTOR inhibitors, which include the downstream effectors of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, the activation of hypoxia-inducible factor (HIF), the PIM kinase family, PTEN expression, elevated superoxide levels, stimulation of autophagy, immune cell response and ERK/MAPK, Notch and Aurora signaling pathways. Moreover, we present an updated analysis of clinical trials available on PubMed Central and www.clinicaltrials.gov, which were pertinent to the resistance to rapalogs. The new frontier of inhibiting the mTOR pathway is to identify agents targeting the feedback loops and cross talks with other pathways involved in the acquired resistance to mTOR inhibitors. The true goal will be to identify biomarkers predictive of sensitivity or resistance to efficiently develop novel agents with the aim to avoid toxicities and to better choose the active drug for the right patient.

Treatment-related fatigue with sorafenib, sunitinib and pazopanib in patients with advanced solid tumors: an up-to-date review and meta-analysis of clinical trials.

Fatigue is the most common symptom associated with cancer and cancer treatment. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) of fatigue in patients (pts) with cancer treated with sorafenib (SO), sunitinib (SU) and pazopanib (PZ). PubMed databases were searched for articles published till August 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. Fifteen studies were included in our analysis. A total of 6,996 pts was enrolled: 2,260 had renal cell carcinomas (RCC), 1,691 non-small cell lung cancers, 1,290 breast cancers, 823 hepatocellular carcinomas, 362 soft tissue sarcomas, 304 gastrointestinal solid tumors, 165 neuroendocrine tumors and 101 melanomas. When stratified by drug, SO registered lower incidence and RR of all and high-grade fatigue when compared to SU, whereas the difference between SO and PZ was significant only for all-grade fatigue (p < 0.001). The difference between SU and PZ was significant for high-grade (p < 0.001) but not for all-grade fatigue (p = 0.52). In RCC pts, PZ showed the lower incidence and RR of all and high-grade fatigue. The differences were significant for SU vs. SO (p < 0.001), SU vs. PZ (p < 0.001) and SO vs. PZ (p < 0.001). Treatment with SO, SU and PZ is associated with an increased incidence of fatigue in pts with cancer. Early and appropriate management is required to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations.

Heterogeneous drug target expression as possible basis for different clinical and radiological response to the treatment of primary and metastatic renal cell carcinoma: suggestions from bench to bedside.

Metastatic disease occurs in a significant percentage of patients with renal cell carcinoma (RCC) and is usually associated with an overall poor prognosis. However, not all of the sites of metastases seem to have the same prognostic significance in patients receiving targeted agents. Indeed, patients with lung-only metastases seem to present a better survival than patients with other sites, whereas liver and bone metastases are associated with a worst prognosis. Some clinical studies suggest that metastatic sites are more responsive than primary tumors. This event may be due to intratumor heterogeneity in terms of somatic mutations, chromosome aberrations, and tumor gene expression, primarily centered around Von Hippel-Lindau (VHL) pathway, such as VHL mutations, HIF levels, vascular endothelial growth factor (VEGF) isoforms, and VEGF receptor levels. Nevertheless, these data do not completely explain the discordant biological behavior between primary tumor and metastatic sites. Understanding the causes of this discordance will have profound consequences on translational research and clinical trials in RCC. In this review, we overview current data on the differences between primary RCC and metastases in terms of drug target expression and clinical/radiological response to targeted agents, thus describing the prognostic role of different metastatic sites in RCC patients.

Sunitinib, pazopanib or sorafenib for the treatment of patients with late relapsing metastatic renal cell carcinoma.

PURPOSE: Late recurrence of renal cell carcinoma is not a rare event. In this retrospective study we investigate the clinicopathological features and the outcome of patients treated with sorafenib, sunitinib and pazopanib for late relapsing renal cell carcinoma. MATERIALS AND METHODS: Data were collected from 21 Italian centers involved in the treatment of metastatic renal cell carcinoma. Late relapse was defined as more than 5 years after initial radical nephrectomy. RESULTS: A total of 2,490 patients were screened and 269 (11%) were included in the study. First line therapy was sunitinib in 190 patients (71%), sorafenib in 58 (21%) and pazopanib in 21 (8%). Median progression-free survival was 20.0 months for sunitinib (95% CI 17.0-25.1), and 14.1 months for sorafenib (95% CI 11.0-29.0) and pazopanib (95% CI 11.2-not reported). On multivariate analysis MSKCC score and metastases to lymph nodes, liver and brain were associated with worst overall survival, while pancreatic metastases were associated with longer survival. Furthermore, age, MSKCC score and brain metastases were associated with worst progression-free survival. CONCLUSIONS: Patients with late relapsing renal cell carcinoma seem to present a characteristic pattern of metastatic spread without showing significant differences in terms of progression-free survival among sorafenib, sunitinib and pazopanib.

High neutrophil-to-lymphocyte ratio persistent during first-line chemotherapy predicts poor clinical outcome in patients with advanced urothelial cancer.

BACKGROUND: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer. METHODS: We retrospectively reviewed 292 patients with unresectable or metastatic urothelial cancer treated with first-line chemotherapy between January 2003 and December 2012. The cutoff values of NLR (>3 vs. <3) were evaluated before therapy and at day 1 of the second and third cycle (follow-up NLR). After univariate analysis, a multivariate analysis was carried out by Cox regression model and included the following variables: Eastern Cooperative Oncology Group (ECOG) performance status (≥ 2 vs. 0-1), visceral disease (present vs. absent), hemoglobin (<12 g/dL vs. >12 g/dL), pretherapy NLR (>3 vs. <3), and follow-up NLR (>3 vs. ≤ 3). RESULTS: Patients with pre- and follow-up NLR of >3 had a median progression-free survival of 3.2 months and a median overall survival of 5.7 months. In multivariate analysis, visceral metastases, pretherapy hemoglobin, and follow-up NLR were significant predictors of progression-free survival [hazard ratio (HR) 1.75, P = 0.0001; HR 1.57, P = 0.0015; HR 2.77, P < 0.0001, respectively], and of overall survival (HR 1.60, P = 0.0023; HR 1.59, P = 0.0024; HR 2.89, P < 0.0001, respectively); whereas pretherapy NLR remained as predictor of overall survival only (HR 1.53, P = 0.0101). CONCLUSIONS: An increased NLR persistent during first-line chemotherapy is an independent predictive factor for patients with advanced urothelial cancer.

Surgical resection does not improve survival in patients with renal metastases to the pancreas in the era of tyrosine kinase inhibitors.

BACKGROUND: The aim of this study was to compare survival of resected and unresected patients in a large cohort of patients with metastases to the pancreas from renal cell carcinoma (PM-RCC). METHODS: Data from 16 Italian centers involved in the treatment of metastatic RCC were retrospectively collected. The Kaplan-Meier and log-rank test methods were used to evaluate overall survival (OS). Clinical variables considered were sex, age, concomitant metastasis to other sites, surgical resection of PM-RCC, and time to PM-RCC occurrence. RESULTS: Overall, 103 consecutive patients with radically resected primary tumors were enrolled in the analysis. PM-RCCs were synchronous in only three patients (3 %). In 56 patients (54 %), the pancreas was the only metastatic site, whereas in the other 47 patients, lung (57 %), lymph nodes (28 %), and liver (21 %) were the most common concomitant metastatic sites. Median time for PM-RCC occurrence was 9.6 years (range 0-24 years) after nephrectomy. Surgical resection of PM-RCC was performed in 44 patients (median OS 103 months), while 59 patients were treated with tyrosine kinase inhibitors (TKIs; median OS 86 months) (p = 0.201). At multivariate analysis, Memorial Sloan Kettering Cancer Center risk group was the only independent prognostic factor. None of the other clinical variables, such as age, sex, pancreatic surgery, or the presence of concomitant metastases, were significantly associated with outcome in PM-RCC patients. CONCLUSIONS: The presence of PM-RCC is associated with a long survival, and surgical resection does not improve survival in comparison with TKI therapy. However, surgical resection leads to a percentage of disease-free PM-RCC patients.

KRAS mutation status is associated with specific pattern of genes expression in pancreatic adenocarcinoma.

AIMS: To evaluate potential differences at a molecular level between KRAS mutant tumors (MT) and KRAS wild-type (WT) pancreatic tumors and the biological and prognostic significance of different KRAS mutations. MATERIALS & METHODS: Expression of a panel of 29 genes was analyzed in KRAS WT and MT tumors. Effects of KRAS mutation and gene expression levels were assessed on patients' survival. RESULTS: MUC6 (p = 0.009), HGF (p = 0.011), VEGFR-2 (p = 0.020) and VEGFB (p = 0.026) were significantly more expressed and SMAD4 was less suppressed (p = 0.003) in WT KRAS. Contrariwise, SHH (p = 0.012) and IHH (p = 0.031) were more expressed in MT KRAS patients. No OS difference was found between WT and MT KRAS tumors. CONCLUSION: KRAS mutation status seems to identify two different subtypes of pancreatic ductal adenocarcinoma with similar outcome but distinct molecular features and probably different therapeutic targets.

Present and future of personalized medicine in adult genitourinary tumors.

The development of targeted agents has completely revolutionized the therapeutic scenario of genitourinary tumors. However, no biomarkers of tumor response or patient tolerability have been validated so far, and the selection of patients who may benefit from these approaches is still empirical. Significant advances in genomic sequencing and molecular characterization of these tumors have allowed identification of complex genomic abnormalities, thus increasing our knowledge on cancer biological landscapes and paving the way to the development of personalized strategies based on the patient's genomic and cancer's molecular profiles. This review is an overview of recent findings and emerging individualized therapies in patients with prostate, renal and bladder cancer, focusing on the promises and limitations of this approach in this setting.

Lgr5 expression, cancer stem cells and pancreatic cancer: results from biological and computational analyses.

AIMS: To determine the relationship between Lgr5 and other stemness markers and pathologic features in pancreatic ductal adenocarcinoma (PDAC) samples. MATERIALS & METHODS: In 69 samples, Lgr5 was analyzed by qRT-PCR together with a panel of 29 genes. Bioinformatic analysis was carried out to identify a possible pathway regulating Lgr5 expression in PDAC. RESULTS: Lgr5 expression was not associated with the expression of tested cancer stem cell markers. Moreover, it was not an independent predictor of survival neither at univariate analysis (p = 0.21) nor at multivariate analysis (p = 0.225). CONCLUSION: Based on the lack of correlation between Lgr5 and tested cancer stem cell markers, Lgr5 does not seem to be a potential stemness marker or prognostic factor in PDAC.

α1-Blockers for the treatment of recurrent urinary tract infections in women with dysfunctional voiding: a prospective randomized study.

OBJECTIVES: To evaluate the therapeutic effects of tamsulosin on recurrent urinary tract infections in women with dysfunctional voiding. METHODS: A total of 155 women with recurrent urinary tract infections and dysfunctional voiding were included and randomly assigned to the following groups: uroflowmetry biofeedback (group 1), α1-adrenoceptor antagonists (group 2), uroflowmetry biofeedback combined with α1-adrenoceptor antagonists (group 3) and no treatment (group 4). Patients were evaluated by the American Urological Association Symptom Index at 3, 6 and 12 months. Urodynamics was carried out in patients of groups 1, 2, and 3 at 3, 6 and 12 months, whereas urodynamics was only carried out at 12 months in group 4. All patients were followed up for 1 year with monthly urine cultures. RESULTS: The incidence of storage and emptying symptoms decreased significantly at 3, 6 and 12 months. Mean flow rate, flow time and voiding volume increased significantly (with a better outcome in patients of group 3), whereas post-void residual urine decreased. Mean opening detrusor pressure and detrusor pressure at maximum flow decreased significantly (with a better outcome in patients of group 3). Mean urethral closure pressure and maximum urethral closure pressure decreased significantly with a more significant decrease for patients in group 3. The prevalence of urinary tract infection decreased significantly in all groups after treatment, and this decrease remained stable during the follow up. CONCLUSIONS: In women with dysfunctional voiding and recurrent urinary tract infection, tamsulosin associated with uroflowmetry biofeedback might be an effective and safe treatment option for improving urinary symptoms and quality of life.

Risk of gastrointestinal events with sorafenib, sunitinib and pazopanib in patients with solid tumors: a systematic review and meta-analysis of clinical trials.

Gastrointestinal (GI) events have been described with sorafenib, sunitinib and pazopanib in cancer patients. We performed an up-to-date meta-analysis to determine the incidence and relative risk (RR) in patients with cancer treated with these agents. PubMed databases were searched for articles published till May 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 6,447 patients were available for the meta-analysis; 2,260 had renal cell carcinoma (RCC) and 4,187, 1,691 non-small cell lung cancers, 599 hepatocellular cancers, 1,066 breast cancers, 165 neuroendocrine tumors, 304 gastrointestinal stromal tumors and 362 soft tissue sarcomas. Diarrhea was the most common GI event. When stratified by tumor type (RCC vs. non-RCC), the difference among the incidences of GI events was significant for diarrhea (p < 0.001) and vomiting (p = 0.006), that resulted higher in RCC patients. In RCC patients, sorafenib registered the lower incidence and RR of all grades GI events. The difference was statistically significant for sorafenib versus sunitinib-related all and high-grade events (p < 0.001) and for sorafenib versus pazopanib all grades GI events (p < 0.001) and high-grade anorexia (p < 0.001). Treatment with VEGFR TKIs sorafenib, sunitinib and pazopanib is associated with a significant increase in the risk of GI events in patients with cancer, and frequent clinical monitoring should be emphasized when managing these three and newer VEGFR TKIs.

Perivascular epithelioid cell tumor (PEC-ome) of the prostate: ultrasound feature in case report.

INTRODUCTION: We describe a rare tumor arising from the prostate gland: Perivascular Epithelioid Cells tumor (PEC-ome). A 54-years old was treated for acute urinary retention with alpha-blockers at presentation due to benign prostate enlargement (65 cc) with asymmetric middle lobe and regular PSA (0.92 ng/ml). After 5 months, patient developed a second acute urinary retention episode and nodules in the left lung; he was treated with transurethral resection of the prostate and left lobectomy. RESULTS: Histological examination of prostate and lung tissue gave the same diagnosis: leiomyosarcoma with atypical morphological features and patient was observed for 4 months. Considering the uncommon diagnosis, pathological review by the uro-pathologist at our Hospital was done. Additional immunohistochemistry was done and both tumors showed similar and typical features of metastatic PEC-ome (T1b N0 M1). Therefore a new staging showed local and distant progression with prostatic mass and small lung metastasis. Three cycles of Gemcitabine and Pazopanib were administered, but 2 months later a new urinary retention occurred, despite chemotherapy. Patient referred to our Hospital for salvage pelvic surgery with lymph node dissection. Final pathological diagnosis was PEC-ome of the prostate stage pT4 pN0 R0 M1. CONCLUSIONS: PEC-ome is a rare but rapidly invasive mesothelial tumor with early metastatic potential. When this tumors originates from the fibromuscular stroma of the prostate it mimics benign prostatic enlargement and causes LUTS. Expert pathology aided by immunoisthochemistry is the cornerstone of diagnosis. There are no pathognomonic imaging on ultrasound or symptoms suggesting the presence of PEC-ome in early stage. A multidisciplinary approach is necessary and radical surgery should be done to treat this aggressive cancer.

Biopsy follow-up in patients with isolated atypical small acinar proliferation (ASAP) in prostate biopsy.

The incidence of prostate cancer (PCA) was evaluated in 155 patients with isolated Atypical Small Acinar Proliferation (ASAP) found on initial prostate biopsy, after a medium-term follow-up (40 months) with at least one re-biopsy. Clinical and histological data were analysed. Cancer was detected in 81 of 155 (52.3%). The cancer detection rate was 71.6%, 91.3%, 97.5%, 100% at the 1st re-biopsy, 2nd, 3rd, and 4th rebiopsy respectively. At the uni- and multivariate analyses, prostate volume (≤ 30 cc), transition zone volume (≤ 10 cc), small core length at the initial biopsy (≤ 10 mm) and few number of cores at initial biopsy (≤ 8) are predictive of cancer. Furthermore, tumour characteristics on the whole surgical specimens was assessed in 30 men: 13 of 30 (43 %) had clinically relevant cancer (volume > 0.5 ml or/and Gleason score ≥ 7, or pT3). Most of relevant cancers were detected in the distal apex, anterior gland and midline. These anatomical sites could be under-sampled at the initial biopsy using the transrectal approach. Our data suggest that follow-up biopsy is recommended in all cases of isolated ASAP detected after biopsy using endfire transrectal probe. The re-biopsy strategy should increase the number of cores (or a saturation biopsy), focusing on area of ASAP in the initial biopsy, but also including the under-sampled areas (anterior gland, distal apex and midline) to detect clinically relevant cancers.

Prostatic fiducial markers implantation by transrectal ultrasound for adaptive image guided radiotherapy in localized cancer: 7-years experience.

OBJECTIVE: we present our 7-years' experience with fiducial gold markers inserted before Image-Guided Radiotherapy (IGRT) focusing on our echo-guided technique reporting early and late complications. MATERIAL AND METHODS: 78 prostate cancer (PCA) patients who underwent fiducial markers placement for adaptive IGRT (period 2007-2014) were selected. Mean patient age was 75 years (range 60-81), mean PSA 7.8 ng/ml (range 3.1-10), clinical stage < T3, mean Gleason Score 6.4 (range 6-7). We recorded early and late complications. Maximum distance between the Clinical Target Volume (CTV) and Planning Target Volume (PTV) was assessed for each direction and the mean PTV reduction was estimated. RESULTS: we describe in details our echo-guided technique of intraprostatic gold fiducial markers insertion prior to adaptative IGRT. We report rare early toxicity (5-7% grade 1-2), a mean PTV reduction of 37% and a very low late toxicity (only 3.4% bladder G3 and 8% rectal G2 side effects). CONCLUSION: Our technique of fiducial gold markers implantation for adaptative IGRT is safe and well-tolerated and it resulted helpful to reduce CTV-PTV margin in all cases; the effects on clinical practice seem significant in terms of late toxicity but further investigations are needed with longer follow-up.

Diagnostic-therapeutic pathway for small lesions of the testis.

Objective of our study was to define a diagnostic-therapeutic pathway for proper treatment of not-palpable testicular masses, that may be benign in 38% of cases. Since the intraoperative diagnosis is difficult to reach in particular in small lesion (< 8 mm) and the risk of tissue loss in frozen section analysis occurs frequently, we propose a diagnostic flow chart for the best management of small testis lesions. This proposed protocol has to be shown in details to physicians and patients, who must understand the clinical implications and the risk to undergo a second radical surgery.