Characterization of EpCAM in thyroid cancer biology by three-dimensional spheroids in vitro model.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy. Nowadays, undifferentiated thyroid cancers (UTCs) are still lethal, mostly due to the insurgence of therapy resistance and disease relapse. These events are believed to be caused by a subpopulation of cancer cells with stem-like phenotype and specific tumor-initiating abilities, known as tumor-initiating cells (TICs). A comprehensive understanding of how to isolate and target these cells is necessary. Here we provide insights into the role that the protein Epithelial Cell Adhesion Molecule (EpCAM), a known TICs marker for other solid tumors, may have in TC biology, thus considering EpCAM a potential marker of thyroid TICs in UTCs. METHODS: The characterization of EpCAM was accomplished through Western Blot and Immunofluorescence on patient-derived tissue samples, adherent cell cultures, and 3D sphere cultures of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) cell lines. The frequency of tumor cells with putative tumor-initiating ability within the 3D cultures was assessed through extreme limiting dilution analysis (ELDA). EpCAM proteolytic cleavages were studied through treatments with different cleavages' inhibitors. To evaluate the involvement of EpCAM in inducing drug resistance, Vemurafenib (PLX-4032) treatments were assessed through MTT assay. RESULTS: Variable EpCAM expression pattern was observed in TC tissue samples, with increased cleavage in the more UTC. We demonstrated that EpCAM is subjected to an intense cleavage process in ATC-derived 3D tumor spheres and that the 3D model faithfully mimics what was observed in patient's samples. We also proved that the integrity of the protein appears to be crucial for the generation of 3D spheres, and its expression and cleavage in a 3D system could contribute to drug resistance in thyroid TICs. CONCLUSIONS: Our data provide novel information on the role of EpCAM expression and cleavage in the biology of thyroid TICs, and our 3D model reflects the variability of EpCAM cleavage observed in tissue samples. EpCAM evaluation could play a role in clinical decisions regarding patient therapy since its expression and cleavage may have a fundamental role in the switch to a drug-resistant phenotype of UTC cells.

Treatment of Large Non-Muscle-Invasive Bladder Cancer: The Potential Role of Neoadjuvant Intravesical Chemotherapy.

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.

Prediction model for testis histology in men with non-obstructive azoospermia: evidence for a limited predictive role of serum follicle-stimulating hormone.

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.

Testicular histology may predict the successful sperm retrieval in patients with non-obstructive azoospermia undergoing conventional TESE: a diagnostic accuracy study.

PURPOSE: 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). METHODS: 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. RESULTS: 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 2 = 96.792, p < 0.0001) and correctly classified 72.8 % of cases with 46.8 % sensitivity and 93.4 % specificity, positive predictive value (PPV) 85.06 %, negative predictive value (NPV) 68.7 %, +likelihood ratio (LR) 7.13, and -LR 0.57. Only testicular histology was significant to the model, while FSH and testicular volume were not. Sperm retrieval rate (SRR) was significantly higher in patients with HYPO compared to patients with SCO or MA (88.2 vs 30.5 and 30.9 %, respectively, p < 0.0001) CONCLUSIONS: This study demonstrates that including testicular histology in a model for predicting sperm retrieval increases its diagnostic accuracy. As histology is not available prior to TESE, this model applies only to patients with previous testicular surgery.

Extra-nuclear TERT counteracts oxidative stress and promotes progression in papillary thyroid carcinoma.

The reactivation of TERT is associated with poor outcome in papillary thyroid cancer (PTC). Extra-telomeric functions of TERT were reported, with a protective role against oxidative stress (OS). The aim of the present study was to explore the extra-nuclear TERT localization in PTC and its role in cancer progression. TERT nuclear export under OS were analyzed in K1 PTC cell line. We investigated the role of different TERT localizations using specific TERT constructs that limit its localization to the nucleus or to the mitochondria. The effect of SRC kinase inhibitor PP2, which reduces TERT nuclear export, was investigated as well. Moreover, TERT localization was analyzed in 39 PTC tissues and correlated with the genetic profile and the level of OS, DNA damage and apoptosis in the tumors and with the clinical characteristics of the patients. We demonstrated that TERT is exported from the nucleus in response to OS induced either from H2O2 or the BRAF inhibitor PLX4720. We proved that extra-nuclear TERT reduces mitochondrial OS and induces mitochondrial fragmentation. Moreover, limiting mitochondrial TERT localization reduced proliferation, migration, AKT phosphorylation and glycolysis and increased DNA damage and p21 expression. Finally, in PTC tissues the fraction of mitochondrial/nuclear TERT resulted inversely correlated with OS and p21 expression and associated with tumor persistence. In conclusion, our data indicate that extra-nuclear TERT is involved in reducing the effect of excessive OS, thus promoting cancer cell survival. Extra-nuclear TERT may thus represent a marker of cancer progression and a possible therapeutic target in PTC.

Radiofrequency ablation is an effective treatment for Bethesda III thyroid nodules without genetic alterations.

Background: Radiofrequency ablation (RFA) is effective in the treatment of thyroid nodules, leading to a 50-90% reduction with respect to baseline. Current guidelines indicate the need for a benign cytology prior to RFA, though, on the other side, this procedure is also successfully used for the treatment of papillary microcarcinomas. No specific indications are available for nodules with an indeterminate cytology (Bethesda III/IV). Aim: To evaluate the efficacy of RFA in Bethesda III nodules without genetic alterations as verified by means of a custom panel. Methods: We have treated 33 patients (mean delivered energy 1069 ± 1201 J/mL of basal volume) with Bethesda III cytology, EU-TIRADS 3-4, and negative genetic panel. The mean basal nodular volume was 17.3 ± 10.7 mL. Results: Considering the whole series, the mean volume reduction rate (VRR) was 36.8 ± 16.5% at 1 month, 59.9 ± 15.5% at 6 months, and 62 ± 15.7% at 1-year follow-up. The sub-analysis done in patients with 1 and 2 years follow-up data available (n = 20 and n = 5, respectively) confirmed a progressive nodular volume decrease. At all-time points, the rate of reduction was statistically significant (P < 0.0001), without significant correlation between the VRR and the basal volume. Neither cytological changes nor complications were observed after the procedure. Conclusion: RFA is effective in Bethesda III, oncogene-negative nodules, with reduction rates similar to those obtained in confirmed benign lesions. This procedure represents a good alternative to surgery or active surveillance in this particular class of nodules, regardless of their initial volume. A longer follow-up will allow to evaluate further reduction or possible regrowth.

A complete dissection of the whole testicular parenchyma is required in most patients with nonobstructive azoospermia to obtain enough good quality testicular spermatozoa for ICSI.

BACKGROUND: Due to the heterogeneous distribution of seminiferous tubules (STs) in patients with nonobstructive azoospermia (NOA), retrieving enough good quality spermatozoa for ICSI may require a complete testicular dissection. According to the only available study in this field, spermatozoa may be found in the testis surface in 34.2% of patients, while a deeper testicular dissection is able to provide spermatozoa for ICSI in 28% of those without spermatozoa in the testis surface. OBJECTIVES: To determine the probability of finding enough spermatozoa for ICSI at the initial wide incision of the testis in a cohort of men with NOA undergoing microdissection testicular spermatozoa extraction (mTESE). MATERIALS AND METHODS: 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 STs: if no/ not enough spermatozoa were retrieved, the deeper portion of the parenchyma was explored. RESULTS: Spermatozoa 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 (HS) in 12.7%, and hyalinosis in 2%. Spermatozoa were obtained from the testis surface in 46 of 276 patients (16.6%), and after a complete dissection in 91 subjects (32.9%). On multivariate logistic regression, only the histopathological subcategory HS was predictive of the chance of retrieving spermatozoa from the surface of the testis (OR 3.24, 95% CI 1.37-7.69, p = 0.007). DISCUSSION: 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. CONCLUSIONS: By enabling the complete exploration of the testicular parenchyma, mTESE is to be preferred to cTESE to retrieve spermatozoa in patients with NOA.

FAM83B is involved in thyroid cancer cell differentiation and migration.

FAM83B has been recently identified as an oncogene, but its role in thyroid cancers (TC) is still unclear. We examined the expression of FAM83B and its possible involvement in cell migration and differentiation, in neoplastic/normal thyroid tissues and in TC human cell lines. FAM83B expression in TC varies according to the tumor histotype, being significantly downregulated in more aggressive and metastatic tissues. FAM83B levels in cell lines recapitulate patients' samples variations, and its total and cytoplasmic levels decrease upon the induction of migration, together with an increase in its nuclear localization. Similar variations were detected in the primary tumor and in the metastatic tissues from a follicular TC. FAM83B knock down experiments confirmed its role in thyroid differentiation and cell migration, as demonstrated by the reduction of markers of thyroid differentiation and the increase of the mesenchymal marker vimentin. Moreover, the silencing of FAM83B significantly increased cells migration abilities, while not affecting the oncogenic RAS/MAPK/PI3K pathways. Our data indicate for the first time a role for FAM83B in TC cell differentiation and migration. Its expression is reduced in dedifferentiated tumors and its nuclear re-localization could favour distant migration, suggesting that FAM83B should be considered a possible diagnostic and prognostic biomarker.

Unilateral Surgery for Medullary Thyroid Carcinoma: Seeking for Clinical Practice Guidelines.

Optimized preoperative diagnostic tools with calcitonin tests, ultrasound features, functional imaging modalities, and genetic testing to detect hereditary forms have led to an increased rate of earlier diagnosis and surgery for medullary thyroid cancer (MTC). This helps to adapt the primary surgery to the tumor stage and avoid surgical overtreatment for localized tumor growth, i.e., deviating from the regularly recommended thyroidectomy with bilateral central lymph node dissection in favor of a limited unilateral approach. To limit primary surgical therapy, it is crucial that the MTC is clinically unifocal, sporadic, and confined to the thyroid, and that calcitonin levels indicate biochemical recovery after surgery. The main requirement for such a limited approach is the availability of frozen section studies that reliably indicate (i) R0 resection of the MTC, (ii) absence of infiltration of the organ capsule, (iii) lack of desmoplasia (i.e., evidence of the metastatic potential of the MTC), (iiii) absence of contralateral disease or precancerous lesions. Informed consent is mandatory from the patient, who has been fully informed of the advantages, disadvantages, and potential risks of not undergoing the "classic" surgical procedure. The aim of this article is to review the guidelines for the management of early-stage MTC.

Oxidative Stress Correlates with More Aggressive Features in Thyroid Cancer.

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.

Post-Surgical Ablative or Adjuvant Radioiodine Therapy Has No Impact on Outcome in 1-4 cm Differentiated Thyroid Cancers without Extrathyroidal Extension.

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.

The thyroid risk score (TRS) for nodules with indeterminate cytology.

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.

Intrasurgical parameters associated with successful sperm retrieval in patients with non-obstructive azoospermia undergoing salvage microdissection testicular sperm extraction.

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 naïve patients with non-obstructive azoospermia.

Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests.

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. 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.

Microsurgical TESE versus conventional TESE for ICSI in non-obstructive azoospermia: a randomized controlled study.

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 > or = 3 x maximum value of normal range (N) (4/12, 1/12), in 17/40 patients with 2N < or = 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) > or = 12 ml (6/9, 5/9), in 27/56 testicles with 8 ml < or = 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.

Minute focus of prostate cancer on needle biopsy: correlation with radical prostatectomy specimen.

OBJECTIVES: To determine if the presence of a single minute neoplastic lesion defined as a lesion < or = 0.5 mm in length and Gleason score < or = 6 at biopsy is a reliable predictor of the presence of a potentially clinically insignificant carcinoma at radical prostatectomy. PATIENTS AND METHODS: 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 volume < or = 0.5 cc, Gleason score < or = 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. RESULTS: In 18 (11.9%) patients the prostate biopsy showed a single neoplastic focus of < or = 0.5 mm in length and Gleason score of < or = 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. CONCLUSION: 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.

First case of bilateral intratubular germ cell tumor in androgen insensivity syndrome.

INTRODUCTION AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Histologic study of tissue reaction to the gastric band: does it contribute to the problem of band erosion?

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.

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

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.

[Pathology and physiopathology of urethral stenosis]. / Anatomia patologica e fisiopatologia delle stenosi uretrali.

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.