Yutaka Kondo

The assessment of oxidative stress in infertile patients with varicocele

To assess oxidative stress markers, antioxidant capacity and cytokines in seminal plasma from infertile patients with varicocele, and to investigate seminal oxidative status and sperm DNA damage after varicocelectomy.

Abnormalities of thyroid function in Japanese patients with metastatic renal cell carcinoma treated with sorafenib: a prospective evaluation.

The objective of this study was to characterize features of thyroid dysfunction in Japanese patients with metastatic renal cell carcinoma (RCC) who were treated with sorafenib. We performed a prospective observational study including 69 Japanese patients who were diagnosed as having metastatic RCC refractory to cytokine therapy and subsequently treated with sorafenib for at least 12 weeks. Thyroid function was assessed before and every 4 weeks after the initiation of sorafenib treatment. Of the 69 patients, 23 (33.3%) did not show any biochemical thyroid abnormality, while the remaining 46 (67.7%) developed hypothyroidism. However, 11 (23.9%) of these 46 hypothyroid patients initially had a suppressed thyroid-stimulating hormone (TSH) value accompanying the increase in free triiodothyronine (T3) and/or free thyroxine (T4) before developing hypothyroidism, suggesting sorafenib-induced thyroiditis. During the observation period of this study, 4 patients (5.8%) demonstrated severe clinical symptoms caused by hypothyroidism and received thyroid hormone replacement. Among several factors examined, only age was significantly associated with the risk for hypothyroidism. These findings suggest that although the incidence of clinically significant hypothyroidism requiring thyroid hormone replacement therapy was not very high, biochemical thyroid abnormality was frequently observed in Japanese RCC patients treated with sorafenib. Accordingly, regular surveillance of thyroid function by the measurement of TSH, free T3, and T4 is warranted during sorafenib treatment in Japanese RCC patients.

Predictors of improved seminal characteristics by varicocele repair

The aim of this study was to investigate predictors of the improvement of semen characteristics after low ligation for patients with varicoceles. The records of 97 oligozoospermic patients who underwent microsurgical left or bilateral inguinal varicocele repair were retrospectively evaluated. We assessed factors that could be predictors of the improvement of semen characteristics using logistic regression analysis. We evaluated age, testicular volume, varicocele grade, serum follicle‐stimulating hormone (FSH), luteinising hormone, testosterone, sperm concentration and motility before low ligation. Among the 97 patients, sperm concentration improved from 6.4u2003±u20035.8 to 24.2u2003±u200335.1u2003millionu2003ml−1 and sperm motility increased from 32.8u2003±u200324.9% to 41.0u2003±u200314.6% in 55 patients (57%). In logistic regression analysis, pre‐operative serum FSH and testosterone concentration were predictors of sperm concentration improvement. Varicocele repair improved sperm concentration and motility. Low serum FSH and high testosterone are significant factors predicting the improvement of semen characteristics before low ligation.

Cisplatin regulates Sertoli cell expression of transferrin and interleukins.

It is well known that exposure to cis-diaminedichloroplatinum (CDDP) results in impairment of spermatogenesis; however, little is known about the signal mechanisms involved in CDDP regulation of Sertoli cell (SC) function. This study was designed to evaluate how CDDP regulates SC signal molecules and mechanisms. Purified rat SC was cultured under serum-free conditions and treated with CDDP (10 ng/ml) at various time points. Western blot analysis was used to determine the activation of extracellular signal-related kinases 1 and 2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), cJun-N-terminal kinase (JNK), cyclooxygenase (COX)-1 and COX-2, inducible and endothelial nitric oxide synthase (iNOS and eNOS). The levels of transferrin (TF) and prostaglandin (PG)E2, PGF2alpha, PGD2, carbaprostacyclin (cPGI2 analog) in culture medium were quantified by ELISA. Nitrite (NO2(-)) and nitrate (NO3(-)) in culture medium were also quantified by Griess assay. Interleukin (IL)-1beta and IL-6 mRNAs were measured by quantitative real-time PCR (QRT-PCR) analysis. CDDP activated the phosphorylation of ERK1/2 (p-ERK1/2) in the early phase (within 5 min) and the level of transferrin (TF) fell significantly. In addition, CDDP significantly increased the level of COX-2, PGs, and ILs in the late phase (within 24h). When ERK activity inhibitor (PD98059, 10 microM) or COX-2 activity inhibitor (NS-398, 10 microM) was used, CDDP reduction of TF and induction of PG and IL expression were prevented, suggesting that the detrimental effects on spermatogenesis through the impairment of SC induced by CDDP are mediated by the activation of ERK1/2 and COX-2 pathways in SC.

Effect of varicocelectomy on patients with unobstructive azoospermia and severe oligospermia

To assess the treatment outcome and benefits after varicocelectomy in men with unobstructive azoospermia (UOA) and severe oligospermia (SO).

Gender as a significant predictor of intravesical recurrence in patients with urothelial carcinoma of the upper urinary tract following nephroureterectomy.

OBJECTIVESnTo retrospectively assess the significance of gender as a predictor of intravesical recurrence following nephroureterectomy for urothelial carcinoma of the upper urinary tract (UC-UUT).nnnMATERIALS AND METHODSnThis study included 502 consecutive patients (360 male and 142 female) who were diagnosed as having clinically localized UC-UUT and underwent nephroureterectomy. Clinicopathologic outcomes of these patients were analyzed focusing on the impact of gender.nnnRESULTSnThe incidence of intravesical recurrence in male patients (41.9%) was significantly greater than that in female patients (27.5%). Despite the lack of significant differences in cancer-specific and overall survivals with respect to gender, the intravesical recurrence-free survival in male patients was significantly worse than that in female patients. Of several parameters examined, univariate analysis identified gender, tumor site, and tumor focality as significant predictors of intravesical recurrence following nephroureterectomy. Of these, only gender and tumor site appeared to be independently associated with intravesical recurrence-free survival on multivariate analysis. Furthermore, there was a significant difference in intravesical recurrence-free survival according to positive numbers of these two independent factors; that is, intravesical recurrence occurred in 12 of 55 patients who were negative for both risk factors (21.8%), 96 of 280 positive for a single risk factor (34.3%), and 82 of 167 positive for both risk factors (49.1%).nnnCONCLUSIONSnThe incidence of intravesical recurrence following nephroureterectomy for UC-UUT is comparatively high. Therefore, it would be potentially important to perform careful follow-up targeting intravesical recurrence for such patients, particularly for male patients and/or patients with tumor located at the ureter.

Rapidly progressing, late-onset obstructive azoospermia linked to herniorrhaphy with mesh

OBJECTIVEnTo report a case of a man presenting with rapidly progressing inguinal vasal obstruction 5 years after bilateral herniorrhaphy with polypropylene mesh.nnnDESIGNnCase report with a review of the scientific literature.nnnSETTINGnMale infertility clinic, Kobe University Hospital (Kobe, Japan).nnnPATIENT(S)nA 30-year-old patient who had undergone bilateral inguinal herniorrhaphy using polypropylene mesh 5 years previously.nnnINTERVENTION(S)nThe patient underwent bilateral vasography and left testicular sperm extraction (TESE).nnnMAIN OUTCOME MEASURE(S)nLong-term effects of the adult inguinal herniorrhaphy with polypropylene mesh.nnnRESULT(S)nRapid progression of vas deferens obstruction occurred within several months. We performed left TESE for intracytoplasmic sperm injection (ICSI) and retrieved many motile sperm.nnnCONCLUSION(S)nBefore azoospermia, men who undergo inguinal herniorrhaphy using polypropylene mesh need to rapidly cryopreserve their sperm for future fertility; TESE-ICSI is also a selectable treatment.

Impact of sorafenib on health-related quality of life in Japanese patients with metastatic renal cell carcinoma: a prospective evaluation

Study Type – Therapy (case series)u2028Level of Evidenceu20034

Inhibition of claudin-11 and occludin expression in rat Sertoli cells by mono-(2-ethylhexyl) phthalate through p44/42 mitogen-activated protein kinase pathway.

Our objectives were to evaluate the effects of mono(2-ethylhexyl) phthalate (MEHP) on tight junctions (TJ) in cultured rat Sertoli cells (SC) and to investigate changes in the signal transduction pathways in SCs following MEHP treatment. SCs were isolated and purified from the testes of 18-day-old Sprague Dawley rats and incubated at 34°C for 3 days. After treatment of SCs with either the vehicle or MEHP for 0.5, 1, 3, 6 and 24 hours, whole cell lysates were isolated from each replicate to prepare RNA and protein. Expression levels of claudin-11, occludin, and zonula occludens-1 (ZO-1) mRNA were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and changes in signal transduction pathways possibly induced by MEHP treatment were assessed by Western blot analyses. MEHP treatment led to significant decreases in the expression of claudin-11 and occludin mRNA, but not that of ZO-1, in rat SCs. Exposure of rat SCs to MEHP resulted in the marked induction of phosphorylated p44/42 mitogen-activated protein kinase (MAPK), whereas other pathways examined in this study were not activated by MEHP. Furthermore, treatment of rat SCs with a specific inhibitor of p44/42 MAPK prevented the MEHP-induced down-regulation of claudin-11 and occludin. These findings demonstrate that MEHP exposure inhibited the expression of claudin-11 and occludin mRNA in rat SCs through the p44/42 MAPK pathway, suggesting the possible involvement of MEHP in spermatogenic function by regulating major components of TJs in SCs.

Age at diagnosis as a powerful predictor for disease recurrence after radical nephrectomy in Japanese patients with pT1 renal cell carcinoma

Objectives:u2003 To review clinical outcomes and to identify clinicopathological variables as predictors of disease recurrence in a cohort of Japanese patients undergoing radical nephrectomy for renal cell carcinoma (RCC).