Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia

background: Despite the improved success rate of sperm retrieval by microdissection testicular sperm extraction (micro-TESE), methods to stimulate spermatogenesis in men with non-obstructive azoospermia (NOA) remain unexplored. The aim of this study was to evaluate the effects of hCG-based hormonal stimulation in men with NOA on the success of sperm retrieval by micro-TESE. methods: Forty-eight men with NOA who had negative sperm retrieval results by the micro-TESE procedure were included. A second micro-TESE was subsequently performed on these men: 20 were not treated by any hormonal therapy, and 28 subjects received daily subcutaneous injections of hCG for 4 -5 months prior to the second micro-TESE. Recombinant FSH was added if endogenous gonadotrophin levels decreased during the hCG stimulation. The sperm retrieval rate at the second micro-TESE; the levels of gonadotrophins, testosterone and estradiol; and the effects of hormonal therapy on testicular histology were evaluated. results: Among the 28 men with hCG stimulation, 15 (54%) showed decreased LH and FSH levels (0.67 + 0.10 and 0.96 + 0.14 mIU, mean + SEM, respectively) due to elevated serum testosterone (9.5 ng/dl). Sperm were obtained at the second micro-TESE from six men who had received hormonal therapy (21%), whereas no sperm were retrieved from untreated men (P , 0.05). Success at the second micro-TESE was more likely if histology at the first micro-TESE showed hypospermatogenesis. conclusions: The Leydig cells of the testis can respond positively to exogenous hCG even under hypergonadotropic conditions. HCG-based hormonal therapy prior to a second micro-TESE attempt is effective in men with hypospermatogenesis

Enhanced diagnostic accuracy for quantitative bone scan using an artificial neural network system: A Japanese multi-center database project

Background Artificial neural network (ANN)-based bone scan index (BSI), a marker of the amount of bone metastasis, has been shown to enhance diagnostic accuracy and reproducibility but is potentially affected by training databases. The aims of this study were to revise the software using a large number of Japanese databases and to validate its diagnostic accuracy compared with the original Swedish training database. Methods The BSI was calculated with EXINIbone (EB; EXINI Diagnostics) using the Swedish training database (n = 789). The software using Japanese training databases from a single institution (BONENAVI version 1, BN1, n = 904) and the revised version from nine institutions (version 2, BN2, n = 1,532) were compared. The diagnostic accuracy was validated with another 503 multi-center bone scans including patients with prostate (n = 207), breast (n = 166), and other cancer types. The ANN value (probability of abnormality) and BSI were calculated. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) analyses were performed. Results The ROC analysis based on the ANN value showed significant improvement from EB to BN1 and BN2. In men (n = 296), the area under the curve (AUC) was 0.877 for EB, 0.912 for BN1 (p = not significant (ns) vs. EB) and 0.934 for BN2 (p = 0.007 vs. EB). In women (n = 207), the AUC was 0.831 for EB, 0.910 for BN1 (p = 0.016 vs. EB), and 0.932 for BN2 (p < 0.0001 vs. EB). The optimum sensitivity and specificity based on BN2 was 90% and 84% for men and 93% and 85% for women. In patients with prostate cancer, the AUC was equally high with EB, BN1, and BN2 (0.939, 0.949, and 0.957, p = ns). In patients with breast cancer, the AUC was improved from EB (0.847) to BN1 (0.910, p = ns) and BN2 (0.924, p = 0.039). The NRI using ANN between EB and BN1 was 17.7% (p = 0.0042), and that between EB and BN2 was 29.6% (p < 0.0001). With respect to BSI, the NRI analysis showed downward reclassification with total NRI of 31.9% (p < 0.0001). Conclusion In the software for calculating BSI, the multi-institutional database significantly improved identification of bone metastasis compared with the original database, indicating the importance of a sufficient number of training databases including various types of cancers. © 2013 Nakajima et al

Sunitinib Versus Sorafenib as Initial Targeted Therapy for mCC-RCC With Favorable/Intermediate Risk: Multicenter Randomized Trial CROSS-J-RCC

Purpose: The present study compared the efficacy of sunitinib and sorafenib as first-line treatment of metastatic clear cell renal cell carcinoma (mCC-RCC) with favorable or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) risk. Patients and methods: Treatment-naive patients with mCC-RCC were randomized to receive open-label sunitinib followed by sorafenib (SU/SO) or sorafenib followed by sunitinib (SO/SU). The primary endpoint was first-line progression-free survival (PFS). The secondary endpoints were total PFS and overall survival (OS). Results: Of the 124 patients enrolled at 39 institutions from February 2010 to July 2012, 120 were evaluated. The median first-line PFS duration was 8.7 and 7.0 months in the SU/SO and SO/SU groups, respectively (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.42-1.08). The total PFS and OS were not significantly different between the SU/SO and SO/SU groups (27.8 and 22.6 months; HR, 0.73; 95% CI, 0.428-1.246; and 38.4 and 30.9 months; HR, 0.934; 95% CI, 0.588-1.485, respectively). The subgroup analysis revealed that the total PFS with SU/SO was superior to the total PFS with SO/SU in the patients with favorable MSKCC risk and those with Conclusions: No statistically significant differences were found in first-line PFS, total PFS, or OS between the 2 treatment arms (ClinicalTrials.gov identifier, NCT01481870)

Fluorescence in situ hybridization for the detection of genetic alterations in prostate and bladder malignancies : Significance as a genetic marker to predict the patient prognosis

Prostate cancer and bladder cancer are common urological malignancies in man, while a lack of basic information underlying the oncogenesis and the tumor progression makes it difficult to form therapeutic strategies against these malignancies. Recent advances of molecular biology revealed that genetic alteration play a crucial role in the oncogenesis and progression of these tumors. Thus, deletions of chromosomes 8p (8p22 and 8p23-pter), lOq (lOq24-qter) and 16q (16q22-qter) were studied on 53 cases of prostate cancer. In 42 patients with transitional cell carcinoma (TCC), chromosomal deletion at 17p (pS3) were investigated. The numerical aberrations of chromosomes 7, 9, 10 and 11 were studied in 37 TCC cases. Forty-one (73%) cases with prostate cancer showed deletions of one or more regions of 8p. The results were confirmed by those of Southern blot study on 11 informative cases. A frequency of deletions of chromosome 8p (LPL and D8S7) were significantly increased in proportion to histopathological grade, while lOq (DlOS27) did not. As for chromosome 16q, the deletion of 16q (D16S155) was strongly associated with aberrant expression of E-cadherin, histopathological grade and tumor metastasis. A significantly higher frequency of progression was observed in patients with LPL deletion than those without deletion. A Cox-Hazard multivariate analysis revealed LPL deletion to be one of the significant prognostic factors as well as stage and D8S7, while neither DlOS27, nor D 16S 155 showed any correlation to disease progression. With regard to bladder cancer, 64% of specimens demonstrated p53 deletion with significant correlation with grade (pThese results suggest that i) non-random numerical aberrations might be early events of oncogenesis in bladder cancer, and ii) specific chromosomal aberrations, such as 8p in prostate cancer, or 17p deletion in bladder cancer, play a crucial role in the development of tumor progression, hence of clinical value as a diagnostic tool to predict the malignant potential and patient prognosis

Klinefelter syndrome: From pediatrics to geriatrics

Abstract Background Klinefelter syndrome (KS) is one of the major causes of nonobstructive azoospermia (NOA). Microdissection testicular sperm extraction (micro‐TESE) is often performed to retrieve sperm. Infertility specialists have to care for KS patients on a lifelong basis. Methods Based on a literature review and our own experience, male infertility treatment and KS pathophysiology were considered on a lifelong basis. Main findings Patients diagnosed early often have an increased number of aberrant X chromosomes. Cryptorchidism and hypospadias are often found, and surgical correction is required. Cryopreservation of testicular sperm during adolescence is an issue of debate because the sperm retrieval rate (SRR) in KS patients decreases with age. The SRR in adult KS patients is higher than that in other patients with NOA; however, low testosterone levels after micro‐TESE will lower the general health and quality of life. KS men face a number of comorbidities, such as malignancies, metabolic syndrome, diabetes, cardiovascular disease, bone disease, and immune diseases, which ultimately results in increased mortality rates. Conclusion A deeper understanding of the pathophysiology of KS and the histories of KS patients before they seek infertility treatment, during which discussions with multidisciplinary teams are sometimes needed, will help to properly treat these patients