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Objectives The effects of human papillomavirus (HPV) infection on male reproductive parameters are currently a matter of controversy. In order to clarify the issue in Japanese infertile men, the prevalence and localization of HPV in semen, sperm parameters, and superoxide dismutase (SOD) activity in seminal plasma were examined in 216 Japanese infertile men. Methods DNA was extracted from liquid-based cytological semen samples. The β-globin gene was amplified by polymerase chain reaction (PCR), and HPV-DNA was amplified using nested PCR with MY09/MY11 as outer primers and GP5+/GP6+ as inner primers. HPV genotyping was performed in the HPV-positive samples. In addition, SOD levels in seminal plasma were analysed quantitatively. In-situ hybridization (ISH) was performed to localize HPV-DNA in sperm from HPV-positive samples. Results Any-risk and high-risk prevalence rates of HPV in semen were 12.5% and 6.9%, respectively. No significant difference in the prevalence of HPV was observed between azoospermic and non-azoospermic subjects. Among non-azoospermic patients, those with HPV detected in semen had significantly lower sperm motility and concentration compared with subjects without HPV detected in semen. SOD levels in seminal plasma were significantly higher in HPV-positive patients compared with HPV-negative patients. ISH analysis of HPV-positive samples revealed that HPV-DNA was localized to the head and mid-piece of sperm. HPV-DNA was present in the sperm of young infertile men. Conclusion HPV infection of sperm was associated with reduced sperm motility and concentration, and resulted in an increase in seminal SOD activity.

Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.

Background/Aim: We evaluated the clinical outcomes of patients with metastatic germ cell tumors (GCT) treated at our hospital, which belongs to a regional cancer center. Patients and Methods: Data pertaining to patients with metastatic GCT were obtained between April 2007-October 2017 and was retrospectively analyzed. Key outcome measures included objective response rates and survival rates.Results: All 42 patients received chemotherapy [complete response: eight (19.0%); partial response: 21 (50.0%); stable disease (SD): nine (21.4%); progressive disease: four patients (9.5%)]. Post-chemotherapeutic surgery was performed for seven out of 21 cases of partial response and two out of nine of stable disease. The 5-year survival rates of patients with good, intermediate and poor prognosis (International Germ Cell Consensus Classification) were 100%, 100%, and 71.4%, respectively. Patients who received induction chemotherapy at other hospitals had significantly poorer prognosis than those at our hospital (p=0.0043). Conclusion: Patients with metastatic GCT should preferably receive chemotherapy at an experienced institution.

Background/aim Pelvic drain (PD) placement is commonly performed after robot-assisted radical prostatectomy (RARP), but the need for PD placement is unclear. This study aimed to assess the need for PD placement after RARP. Patients and methods This retrospective study analysed the effect of PD placement on postoperative complications in patients who underwent RARP between 2009 and 2018. All patients prior to October 1, 2016 had a PD placed; those after did not. Results Of the 308 study patients, 231 received a PD (PD group) and 77 did not (ND group). The incidence of ileus, urinary tract infection and anastomotic leak did not differ significantly between the groups; nor did the incidence of asymptomatic and symptomatic lymphocele at 2 weeks and 1 year after surgery. Multivariate analysis showed that lymph node dissection is a predictor of asymptomatic lymphocele development two weeks after surgery. Conclusion PD placement is not necessary after RARP.

To conduct a prospective randomized trial to evaluate the efficacy of a novel prophylactic procedure for inguinal hernia (IH) after transperitoneal robot-assisted radical prostatectomy (RARP).The prophylactic procedure for IH after RARP involved the dissection of the peritoneum ∼5 cm outward from internal inguinal ring (IIR), separating the spermatic cord and vessels from the peritoneum. This was randomly performed on one side (left or right).A total of 148 cases were included, and IH after RARP was observed in 19 (12.8%) cases, with 11 (7.4%) cases in the right side only, 3 (2.0%) in the left side only, and 5 (3.4%) bilaterally. IHs developed in 9 (6.1%) sides that underwent prophylactic procedure and in 15 (10.1%) that did not. Kaplan-Meier curve analysis revealed no significant difference between the preventive and nonpreventive sides (p = 0.197). Based on the observation during laparoscopic hernioplasty, the prophylactic procedure that strengthened the abdominal wall was by adhesion conglutination of the exfoliated peritoneum in the effective side, and IIRs were opened and developed IH in the ineffective sides. Predictive factors for IH after RARP were not found using Cox proportional hazard model.The preventive procedure for IH used in this study reduced the incidence of IH after RARP, but the difference was not significant.

We performed test clamp procedure in robot-assisted partial nephrectomy (RAPN) to prevent massive bleeding during tumor resection and to omit dissection of non-feeding arteries around the tumor. We subsequently analyzed the safety and usefulness of the procedure. The Test clamp procedure was performed for 1 to 3 min during renal artery test ischemia prior to the actual ischemia and tumor resection. We confirmed the disappearance of blood flow around the renal tumor using color Doppler ultrasonography. If arterial blood flow around the tumor remained, we surveyed the site for other arteries that needed to be clamped and repeated the test clamp procedure until renal blood flow around the tumor disappeared. We retrospectively analyzed consecutive RAPN cases performed from July 2016 to March 2020 at our institutions and reviewed medical records. The clinical data of the RAPN cases were statistically analyzed. Sixty-four RAPN cases underwent the test clamp procedure, which was categorized as the TEST group. Test clamping was performed safely without any clamping-related complications in all cases. Eleven cases (17%) underwent partial ischemia, which was a significantly higher number than that in the control group. Massive bleeding during tumor resection was more frequent in the control group. Postoperative deterioration of estimated glomerular filtration rate did not differ significantly between both groups. Although further investigation was still necessary, our findings indicate that the test clamp procedure may be a safe and secure procedure to perform in RAPN for both patients and surgeons.

Background: Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) has different treatment outcomes across institutions, as seen in conventional TURBT. We retrospectively compared the difference in quality between the two types of endoscopic equipment used for PDD-assisted TURBT in our institution. Methods: This study enrolled 205 consecutive patients who underwent PDD-assisted TURBT. Patients were divided into two groups according to the endoscopic equipment used for PDD-assisted TURBT: Group A using the conventionally used endoscopic system and Aladuck LS-DLED and Group S using the Storz PDD system. Cystoscopy findings of white light (WL), fluorescence light (FL), and combination (positive if either WL or FL was positive) were recorded, and diagnostic quality of PDD was compared between both groups. Results: Group A had 105 cases and 336 specimens, while Group S had 100 cases and 361 specimens, with no significant differences between patient characteristics. The tumor sensitivities of WL, FL, and combination in Group A was 71.9%, 77.1%, 90.5%, respectively, while in Group S, these were 71.5%, 92.2%, 96.1%, respectively. Group S had significantly higher sensitivity of FL and combination than Group A, as well as higher detection of carcinoma in situ lesions. Conclusion: Both endoscopic systems had improved sensitivity with PDD-assistance versus WL only, with Group S having higher sensitivity. Differences in the quality of endoscopic equipment may influence the differences in treatment results with PDD-assisted TURBT across institutions.

Germ cell tumors with somatic-type malignancy (GCTSTM) are rare, and patients with GCTSTM have extremely poor prognoses with a median survival of nine months. Somatic-type malignancy, which are mainly sarcomas, usually exhibit chemoresistance. The recommended therapy for GCTSTM is radical resection; however, Pazopanib, which is a multityrosine kinase inhibitor, has indicated therapeutic effects for some soft tissue sarcoma components. The current study reports the case of a 21-year-old Asian man who presented with GCTSTM after combined chemotherapy for a primary mediastinal germ cell tumor with multiple lung metastases. Despite the metastases, his disease was stable after continuous administration of Pazopanib for two years and then stopping the medication for four years. To the best of our knowledge, the current report is the first report of a durable response by Pazopanib for GCTSTM, which is a rare outcome.

INTRODUCTION AND OBJECTIVE:The patients in some instances experienced hypotension after the oral administration of 5-aminolevulinic acid. In this study, we analyzed the pre- and intraoperative bloo...

Background/aim The best sequential treatment for castration-resistant prostate cancer (CRPC) remains unclear. This study evaluated the therapeutic effects of ethinylestradiol (EE) on CRPC. Patients and methods A total of 80 patients with CRPC, treated with 0.5-1.5 mg/day of EE, were retrospectively assessed. Results The median duration from the initial treatment to the beginning of EE was 48.3 months. A decline in the prostate-specific antigen (PSA) from the baseline was noted in 60 patients (75%) and a >50% PSA decline in 27 patients (34%). The median time of PSA progression, overall survival, and cancer-specific survival after EE were 5.60 months, 24.00 months, and 27.93 months, respectively. Conclusion EE administration for CRPC showed a relatively high PSA response regardless of timing of sequential treatment. The frequency of cardiovascular adverse events was not significantly high. EE administration is a potential treatment option for CRPC.

Although reports have shown evidence for penile length (PL) shortening after radical prostatectomy (RP), the association between neoadjuvant androgen deprivation therapy (NADT) and PL after RP has yet to be determined. This study evaluates chronological changes in PL after NADT and RP. Stretched PLs (SPLs) of 143 patients, 41 of whom had undergone NADT, were measured before, 10 days after, and 1, 3, 6, 9, 12, 18, and 24 months after RP. Chronological erectile function and testosterone levels were then evaluated. SPL was shortest 10 days after RP in both the NADT (-) and NADT (+) groups and gradually recovered in length thereafter. SPL in the NADT (-) group was significantly longer than that in the NADT (+) group before RP. However, no significant differences in SPLs were found between both groups 6 months after RP. Although all subjects in the NADT (+) group had testosterone levels of

Chyloretroperitoneum is a rare complication of urological surgery. Here we report a case of chyloretroperitoneum that occurred in a 28-year-old man post living-donor transplantation. Twenty-nine days post transplantation, perirenal fluid collection and hydronephrosis were detected and percutaneous drainage was performed. The fluid was chylous and revealed a very high triglyceride concentration (1,197 mg/dL). Total parenteral nutrition and administration of octreotide were performed, but the leakage did not improve. On the contrary, the drainage fluid gradually increased to 1,600 mL/day, and a laparoscopic fenestration was performed owing to a concern about the adverse effects of massive lymph loss. Ascites temporarily appeared but disappeared 3 months post fenestration. To our knowledge, this is the first case report of pelvic chyloretroperitoneum post living-donor transplantation. Furthermore, if chyloretroperitoneum treatment using diet control or octreotide is ineffective, laparoscopic fenestration can be considered as a treatment option.

Approximately 15% of couples are infertile, with half of these cases being due to a male factor. Testis-specific cytoplasmic poly(A) polymerase beta (PAPOLB) is known to be critical for spermatogenesis. In mice, the loss of function of the Papolb gene results in the arrest of spermiogenesis and in male infertility. To analyse the role of the PAPOLB gene in human male infertility, this study investigated the relevance of this gene to human Sertoli-cell-only syndrome (SCOS) with azoospermia. Mutation analysis of the PAPOLB coding region was performed on 139 Japanese patients by PCR and direct sequence analysis. No critical mutations directly causing SCOS were detected, but three single-nucleotide polymorphisms (SNPs; SNP1 (c1101C T), SNP2 (c1347T C) and SNP3 (c1903C A)) were found in the coding region. However, there were no significant associations in the allelic and genotypic distributions of these three SNPs between the SCOS and control groups (p.05). This study suggests a lack of association of PAPOLB with azoospermia due to SCOS in humans.

Genetic mechanisms are implicated in some cases of male infertility. Recently, it was demonstrated that male mice lacking the gene for RAD21L exhibited azoospermia caused by meiotic arrest. Mouse RAD21L is a functionally relevant meiotic α-kleisin that is essential for male fertility. Therefore, we hypothesized that RAD21L mutations or polymorphisms may be associated with male infertility, especially azoospermia secondary to meiotic arrest. To determine if RAD21L defects are associated with azoospermia in groups of patients with meiotic arrest, we performed direct sequencing of the RAD21L coding regions in 38 Japanese patients with meiotic arrest and in 200 normal controls. Three coding single-nucleotide polymorphisms (SNP1-SNP3) were detected in the meiotic arrest patient group. Sertoli cell-only syndrome is considered a common cause of non-obstructive azoospermia. For comparison, the RAD21L coding regions in which SNP1-SNP3 were detected were sequenced in 140 patients with Sertoli cell-only syndrome. Statistical analyses were used to compare the two groups of patients with the control group. Genotype and allele frequencies of SNP2 and SNP3 were notably higher in the two patient groups compared with the control group (Bonferroni adjusted p value

OBJECTIVE To analyze perioperative blood pressure in patients undergoing transurethral resection of bladder tumor with photodynamic diagnosis. METHODS A total of 109 consecutive patients who underwent photodynamic diagnosis-assisted transurethral resection of bladder tumor at Kanazawa University, Kanazawa, Ishikawa, Japan, were included in this study and considered as the photodynamic diagnosis group. Clinical data were collected, and perioperative systolic bladder pressure and vasopressor usage were analyzed. In contrast, consecutive patients who previously underwent conventional transurethral resection of bladder tumor (without the use of oral 5-aminolevulinic acid) were used as the control group. RESULTS The systolic blood pressure before anesthesia, lowest systolic blood pressure from the anesthesia induction to the start of operation and lowest systolic blood pressure during operation were significantly lower in the photodynamic diagnosis group. The rate of vasopressor use was significantly higher in the photodynamic diagnosis group. On multivariate analysis, we found that general anesthesia and regular use of renin-angiotensin system inhibitor were associated with an increased risk of hypotension (lowest systolic blood pressure from the anesthesia induction to the start of operation

Background/aim This study aimed to evaluate the therapeutic effect of enzalutamide (ENZ) or abiraterone acetate (ABI) on bone metastasis in castration-resistant prostate cancer (CRPC), using bone scan index (BSI). Materials and methods Treatment outcomes for 31 patients who had undergone ENZ or ABI treatment were examined for CRPC with bone metastases. Cox proportional-hazards regression models were used to investigate the association between overall survival (OS) and clinical characteristics. Results Median OS after ENZ or ABI treatment was 29 months. Considering the flare phenomenon, BSI in 17 (55%) patients decreased following treatment. In multivariate analysis, low baseline BSI value and a decrease in BSI following treatment were associated with longer OS (hazard ratio [HR]=8.009; p=0.35 and HR=7.025; p=0.045*, respectively). Conclusion Low BSI value before ENZ/ABI treatment and a decrease in BSI following ENZ or ABI treatment are independent predictors of longer OS. BSI could be useful for risk assessment of CRPC patients with bone metastases.

BACKGROUND/AIM To evaluate our initial experience with radium-223 chloride (Ra-223). MATERIALS AND METHODS A total of 26 castration-resistant prostate cancer (CRPC) patients with bone metastases, treated with Ra-223 at our hospital were evaluated. This study aimed to observe adverse events (AEs) and changes in serum markers, and Bone Scan Index (BSI). Additionally, the relationship between these values and OS was investigated. RESULTS The observed AEs mainly included fatigue and nausea. Alkaline phosphatase (ALP) and bone-type alkaline phosphatase (BAP) levels decreased following the treatment; however, those of PSA and 1-CTP tended to increase, regardless of Ra-223 administration. Overall survival (OS) was significantly improved in cases with a baseline BSI value of

The azoospermia factor (AZF) region is important for spermatogenesis, and deletions within these regions are a common cause of oligozoospermia and azoospermia. Although several studies have reported this cause, the present research, to the best of our knowledge, is the first large-scale study assessing this factor in Japan. In this study, 1030 male patients with infertility who were examined for Y chromosome microdeletion using the polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) method, a newly developed method for Y chromosome microdeletion screening, were included. The study enrolled 250 patients with severe oligospermia and 717 patients with azoospermia. Among the 1030 patients, 4, 4, 10, and 52 had AZFa, AZFb, AZFb+c, and AZFc deletions, respectively. The sperm recovery rate (SRR) of microdissection testicular sperm extraction in patients with AZFc deletions was significantly higher than that in those without AZF deletions (60.0% vs 28.7%, P = 0.04). In patients with gr/gr deletion, SRR was 18.7%, which was lower than that in those without gr/gr deletion, but was not statistically significant. In conclusion, our study showed that the frequency of Y chromosome microdeletion in male patients in Japan was similar to that reported in patients from other countries, and SRR was higher in patients with AZFc deletion.

Background and objective This study assessed the short-term effects of testosterone replacement therapy (TRT) on some risk predic-tors for arteriosclerosis among men with late-onset hypogonadism (LOH).Materials and methods A total of 25 patients with LOH who received TRT for 6 months and 21 patients without TRT were enrolled in the present study. Information regarding the following parameters were collected: Aging Males’ Symptoms scale, Sexual Health Inventory for Men (SHIM), International Prostatic Symptom Score, waist circumfer-ence, and some laboratory data, including fasting blood sugar, hemoglobin A1c (HbA1c), low-density lipo-protein cholesterol, triglycerides, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein (hs-CRP) values, and arteriosclerosis index (AI), at baseline and after 6 months. Patients in the TRT group had received intramuscular injections of testosterone enanthate (250 mg) every month for 6 months while those in the control group received no testosterone treatment during this trial.Results No significant differences were observed in any baseline patient characteristics between both groups. After 6 months, the TRT group exhibited significant improvements in SHIM scores (from 10.1 to 13.1; p = 0.00563), hs-CRP values (from 0.157 to 0.103 mg/dL; p = 0.00753), and the AI (from 2.10 to 1.95 mg/dL; p = 0.0429), with a significant decrease in AMS scale (from 44.3 to 41.8; p = 0.0388). The control group dis-played no significant changes in all parameters. No patient in the TRT group had additional interventions or medications worsening their urinary symptoms.Conclusions TRT for 6 months among men with LOH contributed to significant improvements in three predictive fac-tors for arteriosclerosis. Further studies including long-term TRT are expected to demonstrate the preven-tive effects of testosterone for arteriosclerosis among Japanese men with LOH syndrome.

Background/aim To evaluate the treatment outcomes, toxicity and health-related quality of life (HRQOL) in prostate cancer (PCa) patients who underwent single-fraction high-dose-rate brachytherapy (single-fraction HDR-BT) with external beam radiotherapy (EBRT). Materials and methods From April 2014 to October 2017, treatment outcomes and toxicity of 85 patients who underwent single-fraction HDR-BT of 13 Gy, followed by 46 Gy EBRT in 23 fractions, were examined. HRQOL of 53 patients was evaluated using the Expanded Prostate Cancer Index Composite (EPIC), International Prostate Symptom Score (IPSS)/QOL index, International Index of Erectile Function 5 (IIEF-5), and 36-Item Short Form Survey (SF-36) scores through one year. Results The median follow-up period was 28.8 months. Only three patients had biochemical recurrence. Toxicities included less than grade 3 lower urinary tract symptoms and grade 1 diarrhea. Urethral stricture, a problem related to late toxicity in conventional HDR-BT, was not observed. The urinary and bowel functions in EPIC scores significantly worsened until three or six months after treatment, respectively. Conclusion Single-fraction HDR-BT with EBRT showed promising biochemical control, tolerant toxicities, and preservation of HRQOL, and can be efficiently performed in a shorter time than conventional HDR-BT.

About 15% of couples wishing to have children are infertile; approximately half these cases involve a male factor. Polo-like kinase 4 (PLK-4) is a member of the polo protein family and a key regulator of centriole duplication. Male mice with a point mutation in the Plk4 gene show azoospermia associated with germ cell loss. Mutational analysis of 81 patients with azoospermia and Sertoli cell-only syndrome (SCOS) identified one man with a heterozygous 13-bp deletion in the Ser/Thr kinase domain of PLK4. Division of centrioles occurred in wild-type PLK4-transfected cells, but was hampered in PLK-4-mutant transfectants, which also showed abnormal nuclei. Thus, this PLK4 mutation might be a cause of human SCOS and nonobstructive azoospermia.

Varicocele repair and testicular sperm extraction (TESE) are most commonly performed for infertile males. Generally, TESE is performed to retrieve spermatozoa in azoospermic patients, and varicocelectomy is used to restore the possibility of spontaneous pregnancy by recovering sperm parameters. Most recently, indications for these treatments have been extended with the spread of intracytoplasmic sperm injection (ICSI). To decrease the DNA damage of spermatozoa, TESE for severe oligozoospermia and varicocelectomy for azoospermia or severe oligozoospermia are considered treatment options. However, there is insufficient data with which to draw conclusions about the efficacy of these treatments; the outcomes appear to show improvement to some extent. To achieve a successful ICSI outcome for the improvement of male factor infertilities, these treatments should be offered to selected patients. During selection, patients, especially those with severe oligozoospermia who frequently have a genetic disord...

We investigated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) among hypogonadal men with osteopenia/osteoporosis.From our previous EARTH study population, 74 patients with a clinical diagnosis of osteopenia or osteoporosis and hypogonadism were included in this study, as the TRT (n = 35) and control (n = 34) groups. The TRT group was administered 250 mg of testosterone enanthate injection every 4 weeks for 12 months. The BMD, waist circumference, body mass index, body fat percentage, and muscle volume were measured at baseline and at 12 months. Blood biochemical data, including total cholesterol, triglycerides, HDL-cholesterol, hemoglobin A1c, and adiponectin values were also evaluated.At the 12-month visit, BMD significantly increased in both groups. However, comparisons on changes of parameter values from baseline to the 12-month visit between the TRT and control groups were significantly different in BMD (5.0 ± 5.0 vs. 3.0 ± 3.2; p = .0434) and in adiponectin value (-0.90 ± 3.33 vs. 0.10 ± 2.04; p = .0192). There were no significant changes in other parameters.TRT for 12 months could improve BMD with a decrease in adiponectin levels among hypogonadal men with osteopenia/osteoporosis.

Objectives Deletions in the azoospermia factor regions are the most common known molecular genetic cause of human male infertility involving spermatogenetic failure. Testing for these deletions in Japanese DNA samples using conventional sequence-tagged site probes occasionally lead to considerable non-specific or faint products in the Japanese population. The aim of the present study was to evaluate the sensitivity and specificity of a newly developed kit for the detection of azoospermia factor microdeletions in the Japanese population. Methods Sequence-tagged site probes were reselected and the Luminex suspension array assay was carried out. Validation was retrospectively carried out with 2014 DNA sequences with known microdeletions, which were divided into four categories. Results Category 1 deletions that corresponded to the conventional classification of azoospermia factor deletion were present in 83 men (4.2%), which can result in intrachromosomal homologous recombination. Kit data confirmed the presence of deletions of this type in DNA sequences known to harbor the azoospermia factor deletions. Category 2 deletions involved cytogenetic abnormalities in 28 men (1.4%), whereas category 3 deletions in 759 men (37.7%) were atypical classifications including the gr/gr deletion. As these deletions are thought to be a result of palindromic units and non-homologous recombination, these microdeletions might impact in the interpretation of some clinical findings. The rest of the 1145 cases (56.8%) were assigned to category 4 as normal variants (polymorphism/no deletion). Conclusions The present findings show that this new kit offers good sensitivity and specificity with the advantage of saving in terms of cost and time.

無精子症は精子形成に関与する多種多様な遺伝子群の異常で惹起されるが，精子形成責任遺伝子は未だ同定されていない．近年，遺伝子変異動物の作成による精子形成障害を示す例が少なからず報告され，精子形成に関与する遺伝子が多岐にわたることが明らかにされている．本稿では，遺伝子の視点から，減数分裂を特徴とする精子形成過程に深く関与する遺伝子群を概説し，無精子症を呈している疾患群から，その原因遺伝子について鳥瞰する．Y染色体長腕上にはAZF（Azoospermia factor）と呼ばれる精子形成領域が存在する．この領域の構造的特殊性を概観し，染色体内再組換えによる欠失機構を解説する．さらに，われわれが開発した日本人により適したY染色体微小欠失検出キットの開発のコンセプトとその使用法について概説する． Azoospermia is caused by abnormality in the various genes involved in spermatogenesis. However, the crucial genes for spermatogenesis have not yet been identified. Recently, targeted knockout and transgenic mice have been generated and considerable knowledge has been accumulated about their phenotype patterns, and a wide variety of genes are known to be associated with sperm formation. First, we review the meiotic and post-meiotic phases and genes expressed during spermatogenesis. Many genes corresponding to various clinical features of azoospermia exist, and we also review azoospermia related genes from clinical aspects. The AZF (azoospermia factor) regions on the Y chromosome long arm are thought to show a major correlation with spermatogenesis. From the genomic point of view, their deletion due to intrachromosomal recombimation is reviewed as a constitutional feature of the Y chromosome. Moreover, we explain how to use a detection kit for the Y chromosome micro deletion which we developed.

Increasing evidence shows a relationship between epigenetic regulation and male infertility. The GTF2A1L gene promoter contains the DNA methylation site of a tissue-specific differentially methylated region (TDMR). Eighty-six patients with non-obstructive azoospermia were assessed for the DNA methylation state of CpG islands in the GTF2A1L promoter using testicular genomic DNA. Based on histological criteria, 26 of the 86 patients had normal spermatogenesis (controls), 17 had hypospermatogenesis and 26 had a Sertoli cell-only phenotype or tubular sclerosis. GTF2A1L TDMR methylation was significantly lower in testes DNA from control samples than from hypospermatogenic samples (P=0.029). Patients with hypospermatogenesis were divided into two subgroups: high DNA methylation (HM, n=5) and low DNA methylation (LM, n=12). The GTF2A1L TDMR methylation rate differed significantly between the HM and LM groups (P=0.0019), and GTF2A1L expression was significantly higher among the LM than in the HM patients (P=0.023). High TDMR methylation was correlated with low GTF2A1L gene expression levels. Both groups demonstrated relatively good outcomes with respect to sperm retrieval, fertilisation, pregnancy and childbirth rates. We observed that aberrant GTF2A1L gene expression was not correlated with fertilisation rates. The testicular sperm extraction (TESE) technique may be used to overcome male infertility due to aberrant TDMR methylation. © 2013 AJA, SIMM & SJTU. All rights reserved.

Renal cell carcinoma (RCC) is one of the most fatal urological malignancies. Approximately 30% of patients with RCC have metastasis at initial diagnosis and another 30% have metastasis after radical nephrectomy. Immunotherapy using interferon-α (IFN-α) and interleukin-2 (IL-2) has been the main treatment for metastatic RCC (mRCC) patients, with this therapy being still occasionally recommended. The aims of this study were to evaluate the efficacy of low-dose IL-2 and to investigate the prognosis of the patients. Study subjects included 37 patients who were clinically diagnosed with mRCC and received low-dose IL-2 therapy between December 1999 and October 2014. We investigated the relationship between prognosis and clinical features. The median overall survival (OS), that was calculated from the first use of cytokine therapy, was 19.8 months, while the median progression-free survival (PFS) was 3.82 months. PFS was prolonged in patients who received IL-2 as first-line therapy or second-line therapy following IFN-α therapy. IL-2 therapy should be used as a first- or second-line therapy following IFN-α therapy. IL-2 may have a lower response if it is used after molecular-targeted therapy or other treatments.

Approximately 20% of men with non-obstructive azoospermia are diagnosed with infertility caused by genetic defects (Miyamoto et al. 2015). These include chromosomal abnormalities, Y-chromosome micr...

Purpose: We identified the endogenous retroviruses associated with TTYs (testis specific transcripts linked to the Y) in the AZFb region. We evaluated the relationship between endogenous retroviruses, and TTY expression patterns and function in spermatogenesis. Materials and Methods: We identified family members of TTYs in the AZFb region using computational screening. After investigating the relationship between the endogenous retrovirus genome and TTY expression patterns we screened genomic polymerase chain reaction products from TTY13 amplified from 790 Japanese men, including 275 with azoospermia, 285 with oligozoospermia and 230 who were fertile. Results: Computational screening revealed that 3 members of the TTY family, TTY9, 10 and 13, were regulated by endogenous retroviruses in the AZFb region. Homologous recombination between long terminal repeat of the TTY13 associated human endogenous retrovirus-K14C resulted in TTY13 deletion events. These deletions were more common in patients with azoospermia and oligozoospermia than in fertile males. Specifically 15.63% of the azoospermia group, 10.88% of the oligozoospermia group and 0% of fertile controls had only the deletion variant, indicating an association between the homologous recombination rate and the severity of spermatogenesis failure that was statistically significant (p

We report a case of myelodysplastic syndrome (MDS) treated effectively with testosterone enanthate. A 70-year-old man was diagnosed with low-risk MDS in 1998, and he was first given methenolone acetate orally because of gradual progression of anemia and thrombocytopenia. However, this treatment was not effective, so we changed the treatment to testosterone enanthate because of his symptoms with late-onset hypogonadism. Three months after testosterone replacement therapy (TRT), anemia and thrombocytopenia had improved, and mean platelet count and hemoglobin had significant increases from 2.36 ± 0.45 × 10(4) to 3.83 ± 0.78 × 10(4) /µL, and from 11.7 ± 0.81 to 15.2 ± 1.00 g/dL, respectively, which contributed to a decrease in platelet transfusion requirement. Since then, the patient has been on a good clinical course. The present case suggests that testosterone enanthate administration could be an alternative treatment for men with MDS, even in the case where treatment with anabolic-androgenic steroids is not successful, and suggests another interesting effect of TRT on platelets.

INTRODUCTION AND OBJECTIVES: The aim of the present study was to evaluate the effect of medical treatment and serum sex steroid levels on sperm retrieval rate in classic Klinefelter cases. METHODS: From June 2002 to September 2013, a total of 89 classic Klinefelter patients whose data had been found were evaluated. Patients age and infertility time were recorded, and serum gonadotropin and sex steroid levels were measured. If serum testosterone level was less than 1.5 ng/ml, hCG treatment was performed for 4 months, and serum hormone levels were measured again. The patients were divided into two groups according to Micro TeSe results and taking medical treatment. Age, infertility time and serum sex steroid hormone level were compared in groups with Student-t test. The effect of medical treatment on sperm retrieval rate was compared by using Pearson Chi square test. Additionally, the effect of male age, infertility time and sex steroid levels on Micro TeSe was evaluated by using correlation test. RESULTS: Patients’ age, infertility time and sex steroid levels are given in the table according Micro Tese results and treatment method. While sperm retrieval rate was 23.9% (11/46) in patients no-performed medical treatment, it was 65.9% (31/47) in medical treatment performed group (Pearson c21⁄420.702, p1⁄40.001). However, there was close and meaningful negative correlation between Micro TeSe results and patients agend infertility time (Age: r1⁄4 -.341, p1⁄40.001; Infertility time: r1⁄4 -.260, p1⁄40.001). CONCLUSIONS: While sperm retrieval rate with micro TeSe was higher in Klinefelter cases after medical treatment and in higher serum testosterone levels, the age of the cases and aging process of the testicular tissue by the year was the most important factors affected sperm extraction in Klinefelter cases.