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Oxidative stress (OS) can have an impact in the pathogenesis and in the progression of thyroid cancer. We investigated the levels of reactive oxygen species (ROS) in 50 malignant and benign thyroid lesions and 41 normal tissues, and correlated them with the thyroid differentiation score-TDS and the clinico-pathologic features. NOX4 expression, GPx activity and the genetic pattern of tumors were evaluated. In malignant and benign lesions, ROS generation and NOX4 protein expression were higher than in normal tissues. Follicular (FTCs) and anaplastic/poorly differentiated cancers had increased OS relative to papillary tumors (PTCs). Moreover, OS in FTCs was higher than in follicular adenomas. Mutated PTCs showed increased OS compared with non-mutated PTCs. In malignant tumors, OS was inversely correlated with TDS, and directly correlated with tumor stage and ATA risk. GPx activity was increased in tumors compared with normal tissues, and inversely correlated to OS. In conclusion, our data indicate that thyroid tumors are exposed to higher OS compared with normal tissues, while showing a compensative increased GPx activity. OS correlates with tumor aggressiveness and mutations in the MEK-ERK pathway in PTC. The inverse correlation between OS and TDS suggests that ROS may repress genes involved in thyroid differentiation.

Due to the heterogeneous distribution of seminiferous tubules in patients with non-obstructive azoospermia (NOA), retrieving enough good quality sperm for ICSI may require a complete testicular dissection. According to a the only available study in this field, sperm may be found in the testis surface in 34.2% of patients, while a deeper testicular dissection is able to provide sperm for ICSI in 28% of those without sperm in the testis surface.to determine the probability of finding enough sperm for ICSI at the initial wide incision of the testis in a cohort of men with NOA undergoing microdissection testicular sperm extraction (mTESE).we evaluated 276 patients, aged 37 (20-62) years, who underwent unilateral (86, 31.15%) or bilateral (190, 68.8%) mTESE from January 2018 through December 2021. During mTESE the entire surface of the testicular parenchyma was explored first in search for dilated seminiferous tubules: if no/ not enough sperm were retrieved, the deeper portion of the parenchyma was explored.Sperm were retrieved in 137 patients (49.6%). Histopathology demonstrated Sertoli-cell only syndrome in 65.6% of operated testes, while maturation arrest was found in 19.5%, hypospermatogenesis in 12.7% and hyalinosis in 2%. Sperm were obtained from the testis surface in 46 out of 276 patients (16.6%), and after a complete dissection in 91 subjects (32.9%). On multivariate logistic regression, only the histopathological subcategory hypospermatogenesis was predictive of the chance of retrieving sperm from the surface of the testis (OR 3.24, 95% CI 1.37-7.69, p = 0.007).most patients with NOA, particularly those with unfavorable histopathological patterns,, require a complete dissection of the testicular parenchyma to obtain enough good quality for ICSI.by enabling the complete exploration of the testicular parenchyma, mTESE is to be preferred to cTESE to retrieve sperm in patients with NOA. This article is protected by copyright. All rights reserved.

Introduction: The COVID-19 pandemic caused an increased mortality in nursing homes due to its quick spread and the age-related high lethality. Results: We observed a two-month mortality of 40%, compared to 6.4% in the previous year. This increase was seen in both COVID-19 positive (43%) and negative (24%) residents, but 8 patients among those testing negative on the swab, tested positive on serological tests. Increased mortality was associated with male gender, older age, no previous vitamin D supplementation and worse “activities of daily living (ADL)” scores, such as Barthel index, Tinetti scale and S.OS.I.A. classification. Conclusion: Our data confirms a higher geriatric mortality due to COVID-19. Negative residents also had higher mortality, which we suspect is secondary to preanalytical error and a low sensitivity of the swab test in poorly compliant subjects. Male gender, older age and low scores on ADL scales (probably due to immobility) are risk factors for COVID-19 related mortality. Finally, mortality was inversely associated with vitamin D supplementation. Design: In this observational study, we described the two-month mortality among the 157 residents (age 60-100) of a nursing home after Sars-CoV-2 spreading, reporting the factors associated with the outcome. We also compared the diagnostic tests for Sars-CoV-2.

Introduction: The endoscopic resection of large and bulky bladder cancers represents a challenge. To reduce the tumor and make it more easy to resect, we used neoadjuvant short and intensive intravesical mitomycin (MMC) therapy. Methods: Patients with large bladder tumors were evaluated for this study. At cystoscopy, the surgeon evaluated the feasibility of complete resection. In patients where this was not possible, biopsies from the tumor, bladder mucosa, and prostatic urethra were taken. These patients then underwent a short and intensive cytoreductive schedule of intravesical MMC. This was then followed by TUR-BT. Results: Fifteen patients were included in our study. The mean age was 74 years (range: 56–82; SD ±6 years). Mean tumor size was 51 mm (range: 35–65; SD ±8 mm). After neoadjuvant treatment, complete resection was then feasible in all patients. The mean tumor volume after the chemo-resection had reduced to 34 mm (range: 10–50; SD ±13 mm). No adverse effects were reported. Conclusion: Intravesical cytoreductive neoadjuvant MMC as an initial treatment of large NMIBC can be considered safe, effective, and feasible.

Whether to conduct remnant ablation or adjuvant radioactive iodine (RAI) therapy in patients with intrathyroidal differentiated thyroid carcinoma (DTC), sized 1.1–4 cm, is debated. We evaluated the impact of RAI on outcome in this category of DTCs. We retrospectively enrolled 308 patients submitted to total thyroidectomy: 198 had tumors sized 1.1–2 cm (Group 1) and 110 of 2.1–4 cm (Group 2). Both groups were divided into patients receiving and not receiving RAI after surgery. RAI+ and RAI− patients did not significantly differ, regarding several clinical and pathological features. Final outcome was defined according to dynamic risk stratification. Remission was observed in the majority of Group 1 and Group 2 patients and outcome did not significantly differ between RAI+ and RAI− patients: respectively, 95.8% vs. 93.7% in Group 1, and 87.7% vs. 86.5% in Group 2. The majority of persistent cases, either RAI+ or RAI−, received therapeutic RAI administration, and about 50% of RAI− cases had an excellent response at final follow up, whereas no RAI+ persistent patients had a beneficial effect. Our findings demonstrate that patients with an intrathyroidal DTC sized 1.1–4 cm do not benefit from RAI. The outcome of these patients remains favorable, and the few patients with persistent diseases can be treated with RAI during follow up.

Study question Is there any intra-surgical parameter able to predict the outcome of salvage microdissection testicular sperm extraction (mTESE) in patients with previous failed TESE? Summary answer Among all the variables under consideration, only the seminiferous tubules (ST) caliber pattern found at high magnification was able to significantly predict the mTESE outcome... What is known already Several studies have demonstrated that no clinical or hormonal parameters are able to predict the outcome of a salvage mTESE performed in patients with previous sperm retrieval failure (SRF). It has been previously demonstrated that a prediction model with the combination of two intra-surgical parameters such as the STs caliber, defined as dilated tubule (DT), slightly dilated tubules (SDT) and not dilated tubules (NDT), and testis histology had an excellent discrimination ability (AUC 0.93) to distinguish between cases with and without the outcome, but such prediction model has not been tested in patients undergoing salvage mTESE. Study design, size, duration A prediction model was built on a dataset of 63 patients, 29–50 years old, undergoing unilateral (15 ) or bilateral (48) salvage mTESE after failed TESE from 2015 through 2019, with a resulting N = 111 testes under consideration. Two models were compared, one with STs and histology as covariates, the other with STs alone: the second model was chosen due to better discrimination... Participants/materials, setting, methods we assessed internal validity with a bootstrapping procedure for a realistic estimate of the performance of the prediction model in similar future patients with NOA undergoing salvage mTESE. We repeated the entire modeling process in 259 samples drawn with replacement from the original sample, and determined the performances (AUC, sensitivity, specificity) of the selected prediction model. Calibration (correspondence between the predicted and observed probabilities) was visually assessed by inspecting the calibration belt... Main results and the role of chance Sperm retrieval was successful in 24 out of 63 patients (38%): age, testis volume and hormonal parameters did not vary among patients with successful sperm retrieval (SSR) or SRF. The prevalent histological pattern was Sertoli cell only syndrome (69.6%), while hypospermatogenesis, maturation arrest and hyalinosis were found in 4.5%, 23% and 1.8% of cases. The STs pattern was heterogeneous, with DTs being found only in 23.4% of testes. Sperm were found in 69% of DTs, 29% of SDTs, and 5% of NDTs. The prediction model correctly classified 82.88% of patients and explained the 26.5% variability of the outcome. The STs pattern significantly predicted the mTESE outcome with a sensitivity of 62% and a specificity of 90.2%, PPV 69.2%, NPV 87%. Both SDT (OR 0.105, 95% CI 0.034–0.317, p Limitations, reasons for caution The STs caliber pattern was subjectively evaluated at high magnification (24–36x) by comparing the individual ST appearance with the surrounding ones, however such evaluation was performed by the same experienced urologist with more than 1000 mTESE procedures performed to date. Wider implications of the findings: No clinical data but the STs appearance at high magnification could discriminate between patients with and without chances of SSR. These results reinforce the evidence supporting the superiority of mTESE compared to conventional TESE in retrieving sperm, particularly in lower prognosis patients with NOA such as those with previous SR. Trial registration number Not applicable

Study question Does the standard, not-dilated seminiferous tubules (STs) diameter vary according with different testis histology patterns in patients with non-obstructive azoospermia (NOA)? Summary answer The standard STs diameter differed significantly among cases with different testis histology: hypospermatogenesis (HYPO) had the highest STs diameter compared to the other histological subgroups. What is known already During microdissection testicular sperm extraction (mTESE), the identification of dilated STs, as subjectively evaluated at high magnification by comparing their apparent caliber with that of the surroundings, is crucial to identify residual foci of intact spermatogenesis and to retrieve sperm. Previous studies have demonstrated that dilated STs contain sperm in most cases, but it is not clear why in some cases an apparent normal tubular caliber does not correspond to spermatogenesis integrity. Aim of the present study was to assess whether different histology patterns could affect the STs diameter. Study design, size, duration We retrospectively evaluated 168 patients with NOA undergoing unilateral (N = 91) or bilateral (N = 77) mTESE from 2018 through 2019. One or more biopsy samples representative of the overall appearance of the testicular parenchyma were taken from one (for unilateral mTESE) or both testes (for bilateral mTESE), was fixed in Bouin’s solution and sent to the pathologist. Histological analysis was conducted by the same experienced pathologist, who examined at least 100 different tubule sections per biopsy sample. Participants/materials, setting, methods Each tubule section (N = 100 per sample) was evaluated at 10X magnification with a micrometer to measure the tubule diameter, then the mean ST diameter was computed. The basal membrane (BM) thickening was evaluated in every section, and a score was assigned by multiplying the degree of BM fibrosis (mild=1, moderate=2, severe=3) for the number of sections (e.g. BM score for moderate fibrosis in 50 sections=2x50=100). Leydig cells hyperplasia (LCH), if present, was also annotated. Main results and the role of chance The median + interquartile range STs diameter was 140; 110–185 mm, while the median BM score was 100; 10–150. Sertoli cell only syndrome (SCO) was found in 51.1% of cases, focal SCO (FSCO) in 4,7%, early (EMA) and late (LMA) maturation arrest in 10.2 and 2.73% respectively, HYPO in 26.17% and hyalinosis (HL) in 5% of cases. LCH was found in 46.88% of samples. STs diameter, BM score and LCH differed significantly among the different histological patterns: STs diameter was 125; 100–148 in SCO, 162; 102–187 in FSCO, 130; 100–175 in EMA, 145; 130–195 in LMA, 205; 170–240 in HYPO and 57.5; 42.5–100 in HL. HYPO samples also had the lowest BM score (20;1–100; p Limitations, reasons for caution The STs were carefully cut before extraction in order to preserve their structural integrity, however the accuracy of such a method of estimating the STs diameter needs to be assessed by further studies. Wider implications of the findings: The identification of dilated STs remains the best strategy to retrieve sperm by mTESE, since larger STs diameters are mostly associated with the more favorable histological patterns. However, dilated STs may be also found in cases with LMA, which explains why in some cases dilated STs do not contain sper. Trial registration number Not applicable

BACKGROUND Patients with non-obstructive azoospermia with a previously failed conventional testicular sperm extraction may undergo a salvage microdissection testicular sperm extraction with the probability of successful sperm retrieval being almost dependent upon the number of previous surgical attempts and to different histopathologic categories. OBJECTIVES To determine whether the seminiferous tubules pattern and the histological categories could affect the sperm retrieval rate in patients with non-obstructive azoospermia undergoing salvage microdissection testicular sperm extraction after failed conventional testicular sperm extraction. MATERIALS AND METHODS Seventy-nine patients undergoing unilateral or bilateral salvage microdissection testicular sperm extraction were evaluated. During microdissection testicular sperm extraction, if present, dilated tubules were retrieved, otherwise, tubules with slightly larger caliber than that of the surroundings were removed. When no dilated tubule or tubule with slightly larger caliber was found, not dilated tubules were excised. A prediction model was built with seminiferous tubules pattern and testis histology as covariates. RESULTS Sperm retrieval was successful in 30 out of 79 patients. The prediction model correctly classified 88.3% of cases, explained the 29.7% variability of the outcome, and significantly predicted the microdissection testicular sperm extraction outcome with a sensitivity of 67.7% and a specificity of 90.2%, Both tubules with slightly larger caliber and not dilated tubules were negatively associated with the chance of retrieving spermatozoa. Among the histological categories, only early maturation arrest was significant to the model (log(SSR) = 0.57 - 1.9SDT - 3.3NDT - 1.76EMA) (where SSR is sperm retrieval rate, SDT is tubule with slightly larger caliber, NDT is not dilated tubule, and EMA is early maturation arrest). The model had a clearly useful discrimination (area under the curve = 0.814), the estimated performance was 0.8105, and internal calibration was acceptable (p > 0.05). DISCUSSION Seminiferous tubules pattern and testis histology may reliably explain the salvage microdissection testicular sperm extraction outcome in all patients with non-obstructive azoospermia apart from those with early maturation arrest, where the homogeneous apparent seminiferous tubules pattern may be misleading. CONCLUSION The outcome of salvage microdissection testicular sperm extraction can be predicted by the same intrasurgical parameters that have been demonstrated to predict the outcome of microdissection testicular sperm extraction in naive patients with non-obstructive azoospermia.

Cytology is the gold standard method for the differential diagnosis of thyroid nodules, though 25–30% of them are classified as indeterminate. We aimed to set up a ‘thyroid risk score’ (TRS) to increase the diagnostic accuracy in these cases. We prospectively tested 135 indeterminate thyroid nodules. The pre-surgical TRS derived from the sum of the scores assigned at cytology, EU-TIRADS classification, nodule measurement, and molecular characterization, which was done by our PTC-MA assay, a customized array able to cost-effectively evaluate 24 different genetic alterations including point mutations and gene fusions. The risk of malignancy (ROM) increased paralleling the score: in the category >4 and ≤ 6 (low suspicion), >6 ≤ 8 (intermediate suspicion), and >8 (high suspicion); ROM was 10, 47 and 100%, respectively. ROC curves selected the score >6.5 as the best threshold to differentiate between malignant and benign nodules (P < 0.001). The TRS > 6.5 had a better performance than the single parameters evaluated separately, with an accuracy of 77 and 82% upon inclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features among malignant or benign cases, respectively. In conclusion, for the first time, we generated a score combining a cost-effective molecular assay with already validated tools, harboring different specificities and sensitivities, for the differential diagnosis of indeterminate nodules. The combination of different parameters reduced the number of false negatives inherent to each classification system. The TRS > 6.5 was highly suggestive for malignancy and retained a high accuracy in the identification of patients to be submitted to surgery.

PURPOSE: The present prediction model was intended to verify whether serum FSH level could be predictive of testis histology in patients with non-obstructive azoospermia (NOA). METHODS: We evaluated two datasets of patients with NOA: the first (San Paolo dataset) comprising 558 patients, 18–63 years old, the second (Procrea dataset) composed by 143 patients, 26–62 years old; bot datasets were combined to obtain a validation set. Multinomial logistic regression was first run with serum FSH and testis volume as independent predictors of testis histology, then, the correctly classified histological subcategories were set as outcome variables of a prediction model in both development and validation sets. RESULTS: Multinomial logistic regression showed that FSH was a significant predictor of testis histology in 58% of cases, although it was unable to correctly classify cases with focal SCO or maturation arrest (MA). A prediction model was then run with hypospermatogenesis (HYPO) and Sertoli-only syndrome (SCO) as outcome variables of a binary logistic regression. FSH significantly predicted both HYPO and SCO, with a sensitivity of 40.9 and 80.7 and a specificity of 84.3 and 46.8 respectively. The model showed a fair discriminative ability (ROC AUC 0.705 and 0.709 respectively) and was adequately calibrated. CONCLUSIONS: Supported by a robust statistical analysis, we conclude that serum FSH level cannot be considered a prognostic marker of spermatogenic dysfunction in patients with NOA ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-019-01613-8) contains supplementary material, which is available to authorized users.

BACKGROUND microTESE proved to be the gold standard surgical approach for patients with non-obstructive azoospermia (NOA), but sperm retrieval rates (SRRs) vary considerably among centers. Some authors compared their SRRs with the pattern of seminiferous tubule caliber found at high magnification, but none provided diagnostic accuracy measures. OBJECTIVE The present retrospective study sought to verify the diagnostic accuracy of the pattern of seminiferous tubule caliber in predicting the sperm retrieval in NOA patients. MATERIALS AND METHODS Data from 143 infertile NOA men undergoing unilateral (64) or bilateral (79) microTESE (222 testes) were retrospectively evaluated. During microTESE, if present, dilated tubules (DTs) were retrieved, otherwise tubules with slightly larger caliber (SDT) (×24) than that of the surroundings were removed. When no DT or SDT were found, not dilated tubules (NDTs) were excised. RESULTS Spermatozoa were retrieved in 95 of 222 testes (42.8%); sperm retrieval was successful in 90% of testes with DTs, in 47% of those with SDTs, and only in 7% of those with NDTs (p

Summary We sought to evaluate the expression of HSP27 and HSP90 chaperones in renal cell carcinomas as a target for cancer therapeutics. A total of 127 clear cell renal cell carcinomas stratified according to the Mayo Clinic SSIGN (size, staging, grading, and necrosis) risk groups (good, 1; poor, 5) and 20 cases with metastases, were available. Immunostaining for both HSP27 and HSP90 was performed on tissue microarrays. Results were detailed per scorable arrays per SSIGN risk groups. Immunolabelling for HSP90 and HSP27 was seen in 109 of 127 (86%) and 114 of 127 (89%) cases, respectively. HSP90 scored 4.9 in 32 cases risked SSIGN 1,3.5 in 41 cases SSIGN 2,4.8 in 11 cases SSIGN 3,4.2 in 22 cases SSIGN 4, and 5.0 in three cases SSIGN 5. HSP27 scored 4.6 in 33 risked SSIGN 1, 3.1 in 43 SSIGN 2, 2.6 in 11 SSIGN 3, 3.6 in 24 SSIGN 4, and 2.7 in three SSIGN 5. Metastases ranged from 2.9–5.0. A trend of increasing value for HSP90 was observed when comparing SSIGN 1–2 versus SSIGN 3–5 risk groups (4.2 versus 4.6 mean values; p = 0.06); no difference has been observed for HSP27 (3.8 to 3.9; p = 0.08). A score modulation of HSPs is observed in renal cell carcinoma and may affect the efficacy of targeted therapy.

The present study sought to determine the diagnostic accuracy of FSH level, testicular volume, and testicular histology in predicting the successful sperm retrieval (SSR) in a large cohort of patients with non-obstructive azoospermia undergoing conventional testicular sperm extraction (TESE).We retrospectively evaluated 356 patients with non-obstructive azoospermia between June 2004 and July 2009. Binary logistic regression was used to evaluate the diagnostic accuracy of our predicting model, identifying sperm retrieval rate as binary dependent variable. The predictive accuracy of all variables individually evaluated was quantified with area under curve (AUC) estimates derived from receiver operating characteristic (ROC) curve.The mean patients' age was 36.8 years. Testicular sperm were retrieved in 158 out of 356 patients (44.3 %). Histological diagnosis of Sertoli cell only syndrome (SCO) was obtained in 216 patients (60.6 %), while 55 patients (15.4 %) had maturation arrest (MA) and 85 (23.8 %) had hypospermatogenesis (HYPO). The binary logistic regression model was statistically significant (χ

Inflammatory processes are important components in the pathogenesis of many human cancers. According to the 'injury and regeneration' model for prostate carcinogenesis, injury caused by pathogens or pro-inflammatory cytotoxic agents would trigger proliferation of prostatic glandular cells, leading to the appearance of epithelial lesions named 'Proliferative Inflammatory Atrophy' (PIA). Inflammatory cells infiltrating the prostate would release genotoxic reactive oxygen species, leading atrophic cells to neoplastic progression. The hypothesis pointing to PIA as risk-lesion for prostate cancer has been extensively investigated at the cellular and molecular levels, but few morphological data are available linking PIA or prostatic intraepithelial neoplasia (PIN) to inflammation or clinical prostatitis. We investigated at the morphological level 1367 prostate biopsies from 98 patients with a recent history of chronic prostatitis, and 32 patients with biopsies positive for carcinoma. Our results show that i) PIA is found more frequently in biopsy cores containing a severe or moderate inflammatory focus, compared to NON-PIA lesions (partial or cystic atrophy); ii) the PIA lesion post-atrophic hyperplasia is more frequently found in tissues showing mild or no inflammation; iii) the extent of PIA per patient correlates with the burden of moderate or severe inflammation, whereas NON-PIA lesions do not; iv) low-grade PIN is in over 90% of cases emerging from normal, non-atrophic glands and is more frequently found in biopsy cores with absent or mild inflammatory burden; v) the inverse relationship between the prevalence of low-grade PIN and the extent of PIA lesions per patient is described by a power law function, suggesting the low likelihood of the concomitant presence of these lesions in the same tissue; vi) NON-PIA lesions correlate inversely with neoplasia in patients with prostate cancer; vii) the total scores of the NIH-CPSI questionnaire correlate with both PIA and inflammation burdens at diagnosis of prostatitis but not after pharmacological intervention. These results point to a positive association between tissue inflammation, clinical prostatitis and the putative cancer risk-lesion PIA, but do not support a model whereby low-grade PIN would arise from PIA.

Isolated testicular metastasis from colorectal cancer is considered an unusual event. In this case report we describe for the first time a metastasis from an adenocarcinoma of the sigmoid colon to a cryptorchid testis. The patient developed a painless testicular nodule three years after the diagnosis of primary sigmoid colon cancer. Recent reports have suggested that the incidence of genitourinary abnormalities in human males has increased over the past 50 years; in particular, cryptorchid testes increase the clinical risk factors for primary or metastatic testicular cancer. In conclusion, there should be awareness of the risk of metastasis of colorectal cancer to the testis in the workup of patients with testicular symptoms. Furthermore, patients with colorectal cancer and cryptorchidism should be managed with a single surgical intervention: when the primary colorectal tumor is removed, the cryptorchid testicle should also be removed to reduce the risk of late metastases.

BACKGROUND It would be of value to identify ongoing spermatogenesis molecular markers which can predict successful sperm recovery in patients with non-obstructive azoospermia undergoing conventional or microsurgical testicular sperm extraction (TESE/microTESE). ESX1 is an X-linked homeobox gene expressed in testis, placenta, brain and lung in humans and specifically in pre- and post-meiotic germ cells of the testis in mice. METHODS We investigated the sequence, expression (by RT-PCR) and epigenetic status (by promoter pyrosequencing) of ESX1 in testicular tissue samples, obtained from 81 azoospermic subjects in the context of surgical sperm extraction, to check a possible association between ESX1 alterations and impaired spermatogenesis, as determined by histological analysis. RESULTS The ESX1 transcript was detected in 100% of cases diagnosed as obstructive azoospermia (33), hypospermatogenesis (18) and incomplete maturation arrest (MA) (2), and sperm recovery was also successful in 100% of these cases. ESX1 mRNA was also detected in 5 of 6 patients with incomplete Sertoli cell-only syndrome, in 4 of 6 subjects with complete MA but in only 3 of 16 cases of complete Sertoli cell-only syndrome (cSCOS), whereas sperm recovery was successful in 4 of 6, 2 of 6 and 5 of 16 of these patients, respectively. In cases of focal spermatogenesis, ESX1 expression and sperm retrieval were concordant in 14 of 19 (74%) cases subjected to TESE, but in only 3 of 11 (27%) men who underwent microTESE. With TESE, but not with microTESE, both samples originated from adjacent testicular areas. The pyrosequencing of the ESX1 CpG island revealed methylation levels that were significantly lower in ESX1 expressors when compared with non-expressors. CONCLUSIONS ESX1 emerges as a potentially reliable spermatogenesis molecular marker, whose clinical value as a predictor of successful sperm retrieval warrants further studies.

Objectives We believe early incontinence after radical retropubic prostatectomy (RRP) is mainly due to the shortening of the sphincter's anatomic and functional length as a result of caudal retraction of the urethral sphincteric complex and disruption of the posterior median fibrous raphe. We illustrate a technique of anatomic and functional reconstruction of the rhabdosphincter (RS) aimed at achieving early continence recovery after RRP. Our modification to the Walsh RRP avoids caudal retraction of the urethrosphincteric complex and reconstructs the posterior fibrous raphe. Methods Prior to completion of the vesicourethral anastomosis, the posterior fibrous tissues of the sphincter are joined to the residual Denonvilliers fascia on the posterior bladder wall 1–2cm cephalad and dorsally to the new bladder neck. The study end point was assessment of early and long-term continence rate. Modified RRP (group 1: 250 patients) was compared with unmodified RRP (historical group 2: 50 patients). A crude comparison of treatment effect was assessed by using Pearson chi-square. Multiple logistic regression was used to assess treatment efficacy at discharge, 1, 3, and 12 mo, while taking into account age, pathologic stage, and Gleason score. Continence was defined as 0–1 pad per day. Results Patients in group 1 achieved significantly better continence at discharge (62.4% vs. 14.0%), 1 mo (74.0% vs. 30%), and 3 mo of follow-up (85.2% vs. 46%); long-term recovery was similar in the two treatment groups (94% vs. 90%). Conclusions The technical modification that we proposed achieved a substantial and significant reduction in time to continence with no adverse effects.

BACKGROUND: An increased risk of testicular cancer in men with infertility and poor semen quality has been reported. Our aim was to investigate the prevalence of testicular nodules and cancer in azoospermic subjects with different spermatogenetic patterns. METHODS: A total of 1443 consecutive infertile men were investigated, out of which 145 (10.0%) were found to be azoospermic. By using clinical examination and testicular ultrasound, 11 out of the 145 patients showed testicular nodules (2.8-26 mm). To obtain spermatozoa for assisted reproduction, 97 subjects required testicular sperm extraction (TESE) and biopsy, including the 11 patients with nodules. They were divided into two groups according to biopsy results: Group A (n = 38) with complete Sertoli cell-only syndrome (SCOS) and Group B (n = 59) with varying spermatogenetic patterns. Ten nodules were found in Group A and one in Group B. RESULTS: In azoospermic men, the overall prevalence of nodules was 7.5%. In complete SCOS, the prevalence of nodules and cancer was 10/38 (26.3%) and 4/38 (10.5%), respectively. Amongst the cancers, one embryonal carcinoma, one seminoma and two in-situ carcinomas were found. CONCLUSIONS: The prevalence of testicular nodules and cancer in azoospermic men with complete SCOS is very high. In these subjects, the role of clinical evaluation, ultrasound and biopsy should be emphasized.

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

Purpose: We retrospectively assessed the number and histology of testicular lesions diagnosed clinically and by ultrasonography in a population of infertile men. Materials and Methods: From October 2000 to January 2003, 560 infertile men underwent physical examination, hormonal assessment (follicle-stimulating hormone, luteinizing hormone, testosterone) and scrotal ultrasonography. Eight men were diagnosed with focal testicular ultrasonographic lesions. In 4 cases there was a palpable lesion and in the other 4 cases the lesion was not palpable, diagnosed by ultrasonography (1 was cryptorchid). Only cases of lesions with clear-cut ultrasonographic edges and no history of recent genital infections were considered for explorative surgery through the groin. Microcalcifications were reported if present. The testicle was only preserved when frozen section examination revealed a benign lesion and the margins were negative. Results: Gynecomastia was not present in any patient. No microcalcifications were observed. Follicle-stimulating hormone was high in all patients (range 19.8 to 66.0 mUI/ml, mean 34.4). Luteinizing hormone levels were variable (range 1.32 to 28 mUI/ml, mean 12.3). Testosterone was normal in all cases (range 2.82 to 6.25 ng/ml, mean 4.2). Ultrasonographic features of the lesions were hypoechoic area (6 patients) and mixed hyper-hypoechoic area (2 patients). Histological outcomes of Leydig cell tumor (in 3 patients), focal Leydig cell hyperplasia (1 patient), fibrosis (1 patient), diffuse Leydig cell hyperplasia (1 patient), classic seminoma (1 patient) and embryonal carcinoma (in 1 patient) were observed. Conclusions: Of 560 infertile patients 8 (1.4%) showed focal testicular lesions, 2 (0.4%) were diagnosed with germ cell tumors and 3 (0.5%) with interstitial cell neoplasms. The malignant tumors were both palpable and in 2 of 3 cases Leydig cell tumors were diagnosed only with ultrasonography.

Inflammatory processes caused by chemical, physical or biological agents are known to be important cofactors in the pathogenesis of human cancer. In the prostate, epithelial tissue damage followed by cell regeneration in the presence of inflammation is believed to be a key event in neoplastic transformation. According to the 'injury and regeneration' model, inflammatory cells infiltrating the prostate release reactive species in response to bacterial/viral infection, uric acid, or dietary prostate carcinogens. Besides inducing inflammation, tissue injury by these and other agents would promote the appearance of proliferative inflammatory atrophy (PIA). A subset of proliferating atrophic cells - possibly showing stem-cell features - may be exposed to the genotoxic insult of free radicals and to an increased rate of mutations and chromosomal aberrations. ultimately leading to neoplastic initiation, promotion and progression. In the last decade, the link between inflammation and cancer and the hypothesis pointing to PIA as a risk lesion for prostate cancer have been extensively investigated at the pre-clinical, clinical, morphological, cellular and molecular levels. In this article., recent reports describing Supportive or negative evidence on the link between prostate inflammation, atrophy and cancer are schematically reviewed.

To determine if the presence of a single minute neoplastic lesion defined as a lesionor = 0.5 mm in length and Gleason scoreor = 6 at biopsy is a reliable predictor of the presence of a potentially clinically insignificant carcinoma at radical prostatectomy.We searched in our series of 151 consecutive patients submitted to radical retropubic prostatectomy from September 2003 to April 2007 for patients with a single minute focus of cancer at prostate biopsy. In all bioptic samples we calculated the total length of cores, length and percentage of neoplastic areas and Gleason grade. Total PSA and PSA density was obtained in all patients. Potentially clinically insignificant cancers at radical prostatectomy were defined as those with a tumor volumeor = 0.5 cc, Gleason scoreor = 6 and organ confined disease. The clinical and pathological characteristics of patients with minute prostatic lesion were compared with other prostate cancers by using the 2-sample t-test and chi square test.In 18 (11.9%) patients the prostate biopsy showed a single neoplastic focus ofor = 0.5 mm in length and Gleason score ofor = 6. At definitive histological analysis of the RRP specimen only 5 patients (27.7%) presented a neoplasia potentially clinically insignificant. These patients on the preoperative criteria didn't show any statistically significant difference from the group with clinically significant neoplastic lesion at radical prostatectomy as far as prostate volume, total PSA, PSA density and total length of bioptic core.The weak correspondence between the presence of neoplastic lesions of minimal entity at prostate biopsy and potentially clinical insignificant carcinoma at radical prostatectomy has also been confirmed by our data: only 30% of patients with a single minute focus of well differentiated prostate cancer at biopsy showed at definitive pathology a potentially clinically insignificant cancer. Moreover the parameters we considered as possible predictive factors of clinically insignificant carcinoma did not demonstrate to be reliable criteria in order to identify these patients.

In a population of non-obstructive azoospermia patients, the efficacy of microsurgical testicular sperm extraction (microTESE) and conventional TESE was evaluated in a randomized controlled study on 138 testicles, classified and paired in a 48-square table according to the different classes of the following three variables: patient plasma FSH concentration, orchidometry and testicular histology. Sperm retrieval was positive in 21/22 testicles with hypospermatogenesis (11/11, 10/11; microTESE, TESE respectively), in 12/14 with maturation arrest (6/7, 6/7), in 16/22 with incomplete Sertoli cell-only syndrome (8/11, 8/11), and in 16/80 with complete Sertoli cell-only syndrome (11/40, 5/40). Sperm recovery was positive in 5/24 patients with FSH concentration ≥ 3 × maximum value of normal range (N) (4/12, 1/12), in 17/40 patients with 2N ≤ FSH < 3N (9/20, 8/20), in 30/48 patients with N < FSH < 2N (17/24, 13/24), and in 13/26 patients with FSH = N (6/13, 7/13). Regarding orchidometry, sperm recovery was positive in 11/18 testicles with volume (V) ≥ 12 ml (6/9, 5/9), in 27/56 testicles with 8 ml ≤ V < 12 ml (15/28, 12/28), and in 27/64 testicles with V < 8 ml (15/32, 12/32). FSH value and the surgical procedure were the two variables significantly ( P < 0.05) predicting positive sperm retrieval.

Androgen insensivity syndrome is an X-linked recessive disorder caused by a mutation of the androgen receptor gene localized in Xq 11-q12-b. Affected males have a female phenotype with undescended testis. Aim of the study is the description of the first case of bilateral intratubular germ cell tumor in androgen insensivity syndrome.In September 2002, a 24-year-old woman with XY karyotype and childhood diagnosis of complete testicular feminization first came under our observation. An abdominal ultrasound showed, in correspondence with the inguinal canal, bilaterally, two oval formations with a diameter of about 45 x 20 mm, referable to gonads. Only for the right gonad, furthermore, the presence of a round anechoic image could be seen, of about 1.5 cm and small multiple microcalcifications (6). Explorative laparoscopy and bilateral orchiectomy were carried out.Histological examination revealed the presence of a bilateral intratubular germ cell tumor. A review of the literature on this subject did not yield any adjuvant therapy or standardized follow-up for these patients. We thought it advisable not to carry out any adjuvant therapy, and to follow the patient with abdomen/pelvic CT scans. The current follow-up after four years is negative for relapses.Post-pubertal bilateral orchiectomy, considering the relevant chances of neoplastic progression of the undescended testis, is the therapy chosen for patients with androgen insensivity syndrome. In patients with TIN, orchiectomy is a valid therapeutic option, followed by a strict follow-up abdomen/pelvic CT scan, chest XR, tumor markers every three months for the first two years.

The aim of this study is to evaluate the feasibility of testicular sperm extraction (TESE) in a cancerous testicle during orchiectomy for testicular neoplasm. This is a retrospective study and includes case histories of four azoospermic patients with incidental testicular cancer. None of the patients had fathered children prior to surgery and all patients were strongly motivated by the desire to have offspring. Patients underwent surgical exploration via inguinotomy and spermatic cord clamping. After nodule excision, micro-TESE was performed from the same albugineal incision, under microscopic guidance. Frozen section examination was not performed in the case of large nodules (>3 cm in diameter). Two patients showed classic seminoma and underwent orchiectomy. In two patients, a Leydig cell tumour was found (one patient underwent orchiectomy for large nodule size). Micro-TESE was performed in four patients. Spermatozoa were found in three patients and the retrieved sperm was cryopreserved. One ICSI cycle was performed, but pregnancy failed. In azoospermic patients with testicular nodules, TESE in the cancerous testis is feasible and may avoid further surgery, without any oncological risk.

Background: One of the major complications of gastric banding is intragastric migration of the band. The frequency ranges from 0.5% to 3.8%, and removal of the band is always required. We undertook a prospective study with the aim to determine the reasons for this significant complication in bariatric surgery. Methods: 480 morbidly obese patients underwent adjustable gastric banding in our Surgical Department, from February 1998 to October 2005. 31 of them were reoperated for different surgical problems, at an average time of 39 months after the bariatric procedure. During the reoperation, some fragments of fibro-adipose tissue in close contact with the band were removed. They were examined, focusing on the following parameters: acute and chronic inflammation, fibrosclerosis, and foreign body granulomatous reaction. Results: Histological assessment showed the presence of acute and chronic inflammation, generally of mild and medium grade; fibrosclerosis was present mostly in a severe form, indicating a biological periprosthesic wall that separates and protects the gastric wall from the band; no cases of foreign body reaction were observed, nor were silicone inclusions found inside the inflammatory cells. Conclusion: The histologic changes of periprosthesic tissue do not appear to account for endoluminal migration of the gastric band. Thus, band erosion could have a closer correlation with other causes, such as infection of the band or intraoperative surgical damage, possibly due to direct mechanical action or to the thermal effect of the electric scalpel.

The natural history of Leydig cell testicular tumors is not well known, and differentiation between malignant and benign forms is not easy. We performed a retrospective multicenter evaluation of clinical and histological characteristics as well as followup of Leydig cell tumors.From 1990 to August 2004 surgery was performed on 24 Leydig cell tumors. Before surgery all patients underwent clinical examination, tumor markers (alpha-fetoprotein, beta-human chorionic gonadotropin, lactate dehydrogenase), scrotal ultrasound and chest x-ray. Surgery was performed under ultrasound or palpation guidance via inguinotomy with clamping of the spermatic cord. Lesions less than 3 cm in diameter were resected and sent for frozen section examination. Histological criteria were considered. Abdominal computerized tomography or ultrasound and chest x-ray were performed postoperatively every 3 months for the first 2 years and every 6 months thereafter.Patient age range was 22 to 61 years (mean 37.75). In 7 patients (29.2%) the lesion was palpable and incidental diagnosis was made in 10 patients (41.7%). In the other patients diagnosis was made by ultrasound performed for testicular pain (4 patients, 16.6%) or the appearance of gynecomastia (3 patients, 12.5%). Frozen section examination was done in 20 of 24 patients (83%). In 17 of 20 patients (85%) Leydig cell tumor was diagnosed on frozen section examination. All patients underwent radical orchiectomy. All definitive diagnoses interpreted the neoplasia as benign. Average followup was 117 months (range 11 to 241). There was no disease recurrence or progression and all patients are currently disease-free.In our case study all Leydig cell tumors were interpreted as benign and long-term followup was negative.

Objectives The various prostate biopsy methods are usually compared in terms of the diagnosis rate of prostate cancer. However, the prevalence of cancer in patients with a negative prostatic biopsy is not usually known. We determined the sensitivity and detection rate of 12-core transperineal biopsies in patients not previously investigated for prostate cancer. Methods We performed prostate biopsy in 63 patients (median age 67 years) before radical cystoprostatectomy for high-grade bladder cancer. We then assessed the relationships between biopsy result, prostate cancer in the surgical specimen, and other variables. Results 17.2% of patients had a positive biopsy and 54% had prostate cancer on definitive histology. Biopsy sensitivity was 32.3% overall, 75% for clinically significant cancers, and 11% for non-significant cancers. Median PSA was 1.2ng/ml, PSA levels did not correlate with the presence of prostate cancer, the presence of clinically significant cancer, bioptic diagnosis, or prostate volume. Age correlated with risk of cancer. Conclusions According to autopsy series, the prevalence of prostate cancer is greater than 50% in males older than 60, yet low PSA levels do not reliably indicate disease absence. The sensitivity of double sextant biopsy is unsatisfactory overall (32%), but acceptable (75%) for diagnosing clinically significant cancer.

Mutations in the orphan nuclear receptor DAX1 (NR0B1) cause X-linked adrenal hypoplasia congenital (AHC), a disorder characterized by primary adrenal failure, hypogonadotropic hypogonadism. and azoospermia. We tested the hypothesis that DAX1 somatic mutations in human testis may cause azoospermia. DAX1 sequencing analysis in 15 testicular biopsy samples from men with idiopathic nonobstructive azoospermia did not reveal mutations in the coding region of the gene. We conclude that somatic abnormalities in DAX1 are absent or uncommon in these patients.

Intra-abdominal cystic lymphangioma is a rare dysembryogenetic tumour. Although laparoscopic treatment may be feasible and has been reported in the literature, the extension of the mass to the retroperitoneum can make a minimally invasive surgical approach difficult or impossible. We describe the case of a patient with lymphangioma with retroperitoneal extension who underwent successful surgical therapy.

Primary tumors of seminal vesicles are rare. We report on a benign tumor of the seminal vesicle with fibroepithelial and cystic features. We performed a laparoscopic transperitoneal approach. The mass, not fixed to any anatomical structures except to the prostate, was isolated and removed. Histological examination of tumor revealed two distinct components: epithelial and stromal. We consider the term fibroadenoma more appropriate than cystoadenoma, because the stroma is not reactive but a distinct neoplastic component.

The research of new techniques for surgical repair of urethral stenosis, has developed interest and knowledge toward tissue handling and transfer in urology. Successful surgical repair of "long" stenosis is possible nowadays, using graft or flap tissue transfer. The knowledge of methral anatomy and of histopathology urethral anatomy, histopathology and physiopathology of the mechanism involved in process of urethral narrowing, is necessary for the diagnosis and the surgical indication of this pathology. To review physiopatological and anatomopathological aspects of urethral stenosis is the aim of the authors.

480 Background: Heat shock proteins (HSP) HSP27 and HSP90 are expressed in response to a wide variety of insults, thus allowing the cell to adapt to stress. In cancer cells, both HSP27 and HSP90 may participate to carcinogenesis, suggesting these chaperones as an appealing target for cancer therapeutics. The role of HSP in the development and progression of renal-cell carcinomas (RCCs) remains to be defined. We sought to evaluate a series of clear cell RCCs. Methods: 388 RCCs with clear cell histology available on 10 tissue microarrays were recruited. Each case was represented by 3 neoplastic cores. All these cases were stratified according to the Mayo Clinic SSIGN (Size, Staging, Grading, Necrosis) score into five prognostic groups with increasing worse prognosis (1 to 5). Immunostainings for HSP27 and 90 were performed. A mean score number from the three cores was set per case (percentage x intensity). Results were detailed per number of scorable cases per SSIGN category (1 to 5). Results: 117 and 122 RCCs were respectively available for HSP90 and HSP27 scoring. The remaining samples were lost due to the lack of tissue sections or to the absence of adequate neoplastic cells scorable. HSP90 scored 4,9 in 32 with SSIGN1, 3,5 in 41 SSIGN2, 4,8 in 11 SSIGN3, 4,2 in 22 SSIGN4 and 5 in 3 SSIGN5 patients. HSP27 scored 4,6 in 33 with SSIGN1, 3,1 in 43 SSIGN2, 2,6 in 11 SSIGN3, 3,6 in 24 SSIGN4 and 2,7 in 3 SSIGN5 patients. A significant trend of increasing value for HSP90 has been observed when comparing cases tabled SSIGN1-2 versus SSIGN3-5 (4,2 to 4,6 mean values) (p=0.05); a minor stratification has been observed for HSP27 (3,8 to 3,9) (p=0.08). Conclusions: In conclusion, HSP90 and HSP27 are variable immunoexpressed in a subset of clear cell RCCs, with a trend to higher prognostic SSIGN score. At light of new emerging targeted-therapies in kidney cancer, we report an increasing suitability of these patients to therapies that target the pathways of heat shock protein molecules. Additional learning of the HSP role in clear cell RCCs carcinogenesis is required to guide future therapeutic developments.