Identification and characterization of the antigen recognized by the germ cell mAb TRA98 using a human comprehensive wet protein array.

TRA98 is a rat monoclonal antibody (mAb) which recognizes a specific antigen in the nuclei of germ cells. mAb TRA98 has been used to understand the mechanism of germ cell development and differentiation in many studies. In mice, the antigen recognized by mAb TRA98 or GCNA1 has been reported to be a GCNA gene product, but despite the demonstration of the immunoreactivity of this mAb in human testis and sperm in 1997, the antigen in humans remains unknown, as of date. To identify the human antigen recognized by mAb TRA98, a human comprehensive wet protein array was developed containing 19,446 proteins derived from human cDNAs. Using this array, it was found that the antigen of mAb TRA98 is not a GCNA gene product, but nuclear factor-κB activating protein (NKAP). In mice, mAb TRA98 recognized both the GCNA gene product and NKAP. Furthermore, conditional knockout of Nkap in mice revealed a phenotype of Sertoli cell-only syndrome. Although NKAP is a ubiquitously expressed protein, NKAP recognized by mAb TRA98 in mouse testis was SUMOylated. These results suggest that NKAP undergoes modifications, such as SUMOylation in the testis, and plays an important role in spermatogenesis.

[A Rare Case of Adrenal Metastasis Diagnosed before Discovery of Invasive Ductal Breast Cancer which was Confirmed to Be the Primary Site].

A 54-year-old female underwent open left adrenalectomy for a left adrenal tumor in 2013. The pathology showed metastatic poorly differentiated adenocarcinoma. Despite a close examination, the primary tumor could not be identified. During the follow-up, a computed tomographic scan showed a hyper vascular tumor in the left breast in2015. A left mastectomy was performed for diagnosis and treatment. The pathology showed invasive ductal carcinoma of the breast. Comparing the histopathology and immunohistochemistry of the breast tumor with the adrenal tumor, the adrenal tumor was finally confirmed as metastatic invasive ductal carcinoma. Adrenal gland metastasis from invasive ductal carcinoma is said to be extremely rare. To our knowledge, there have been no reports of cases in which metastatic invasive ductal carcinoma of the adrenal gland was found before the primary site. We report this case with some literature review.

The expression of human testis-specific actin capping protein predicts in vitro fertilization outcomes: A novel biomarker of sperm function for assisted reproductive technology.

PURPOSE: Sperm function tests do not adequately assess fertilization potential, and new indices are required. We have previously reported that human testis-specific actin capping proteins may be involved in both sperm morphology and function. This study aimed to determine whether testis-specific actin capping proteins can be a predictive marker of IVF success. METHODS: Ninety-seven infertile couples who underwent IVF at an infertility clinic were included. Sperm were immunohistochemically stained to evaluate capping protein expression, and the percentage of sperms with normal staining was calculated. The relationship between actin capping protein expression and IVF outcomes was examined. RESULTS: The couples were divided into four groups according to the percentage of normally expressing actin capping protein as follows: ≥90% Group Ⅰ, 80%-90% Group Ⅱ, 70%-80% Group Ⅲ, and <70% Group Ⅳ. Multiple regression analysis showed a significant trend in fertilization rates across the 4 groups (p for trend =0.008).There was no significant trend in pregnancy rates (p for trend =0.276). CONCLUSION: The human testis-specific actin capping protein may be a marker of male contributing factors that predict IVF outcomes.

[A Case of IgG4-Related Disease Arising in Female Periurethra].

A 67-year-old female, with a past medical history of IgG4-related Mikulicz disease, was referred to our department for a periurethral mass revealed by contrast-enhanced computed tomography. She presented with weak urine flow a half year before the first consultation. Magnetic resonance imaging (MRI) revealed a periurethral mass, 39×39×29 mm, extending from the bladder neck to the urethral meatus. Serum IgG4 level was elevated to 580 mg/dl. Histological examination by the transvasinal biopsy revealed a lymphocytic infiltrate with IgG4-positive plasmacytoid predominance, leading to the diagnosis of IgG4-related disease arising in the periurethra. She was treated with prednisolone for 4 months, and urinary disturbance disappeared. MRI showed that the periurethral mass decreased in size.

[Pediatric Multiple Endocrine Neoplasia Type 2B with Pheochromocytoma Diagnosed after Perforation of a Colonic Diverticulum : A Case Report].

A 12-year-old girl was found to have decending colon diverticulum perforation and retroperitoneal abscess on computed tomography (CT) carried out to determine the cause of fever and stomachache. CT-guided drainage tube placement was performed. She was suspected of having MEN2B from her specific facial appearance, Marfan-like body shape and lingual mucosa neuroma. Cervical ultrasonography and serum tumor marker revealed medullary thyroid carcinoma and metastasis to cervical lymph node. Genetic examination revealed a mutation of RET gene codon 918. Therefore, she was diagnosed as having MEN2B. Laboratory data showed elevated urinary catecholamines. Metaiodobenzylguanidine (MIBG) adrenal scintigraphy showed bilateral adrenal uptake and a definitive diagnosis of bilateral adrenal pheochromocytomas was made. Discharge from the drainage tube persisted and it was difficult to continue conservative treatment. Therefore, laparoscopic bilateral adrenalectomy and transverse colon colostomy were performed. Subsequently, total thyroidectomy and cervical lymph node dissection were performed. At five years of follow up, bilateral lung metastases were observed, but the serum calcitonin level was normal and the patient is under observation.

Failure to achieve castrate level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer.

We report the failure to achieve castrate level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. A 76-year-old man was admitted to our hospital for evaluation of an elevated serum prostate specific antigen (PSA) level (191.10 ng/ml) in August 2011. He was diagnosed with T3aN0M1b prostate adenocarcinoma. A combined androgen blockade using luteinizing hormone-releasing hormone agonist (the 1-month depot of leuprorelin acetate) and antiandrogen was administered. Due to liver dysfunction, antiandrogens, both bicalutamide and flutamide, were stopped. The 1-month depot was switched to the 3-month depot in May 2013, but the patient complained of induration and abscess at the infection site. Leuprorelin acetate was replaced by goserelin acetate. Because no adverse event appeared after injection of the 1-month depot of goserelin acetate, the 3-month depot was administered in October 2013. The PSA level increased gradually, and the testosterone level was greater than 50 ng/dl, that is, above castrate range. The 3-month depot of both leuprorelin acetate and goserelin acetate was not effective for this patient. For this reason, the 1-month depot of leuprorelin acetate was started resulting in a rapid decrease in PSA and testosterone levels. Thereafter, androgen depriving therapy could be continued. Androgen deprivation therapy is the standard treatment for patients with advanced prostate cancer and luteinizing hormone-releasing hormone aims to suppress serum testosterone to castrate range. We recommend assessing the serum testosterone levels during luteinizing hormone-releasing hormone agonist therapy for monitoring treatment efficacy and verifying progression when the PSA level increases.

Physiological role of actin regulation in male fertility: Insight into actin capping proteins in spermatogenic cells.

BACKGROUND: During spermatogenesis, cytoskeletal elements are essential for spermatogenic cells to change morphologically and translocate in the seminiferous tubule. Actin filaments have been revealed to be concentrated in specific regions of spermatogenic cells and are regulated by a large number of actin-binding proteins. Actin capping protein is one of the essential actin regulatory proteins, and a recent study showed that testis-specific actin capping protein may affect male infertility. METHODS: The roles of actin during spermatogenesis and testis-specific actin capping protein were reviewed by referring to the previous literature. MAIN FINDINGS RESULTS: Actin filaments are involved in several crucial phases of spermatogenesis including acrosome biogenesis, flagellum formation, and nuclear processes such as the formation of synaptonemal complex. Besides, an implication for capacitation and acrosome reaction was also suggested. Testis-specific actin capping proteins are suggested to be associated with the removal of excess cytoplasm in mice. By the use of high-throughput sperm proteomics, lower protein expression of testis-specific actin capping protein in infertile men was also reported. CONCLUSION: Actin is involved in the crucial phases of spermatogenesis, and the altered expression of testis-specific actin capping proteins is suggested to be a cause of male infertility in humans.

Combination therapy with antioxidants improves total motile sperm counts: A Preliminary Study.

PURPOSE: Optimal strategies to treat idiopathic male infertility have remained unclear. The aim of this study was to evaluate the effectiveness of combination antioxidant therapy with several vitamins and supplements on semen parameters. METHODS: Thirty-one men with oligozoospermia and/or asthenozoospermia evaluated by a Makler counting chamber were randomly assigned to two treatment groups: a combination of antioxidant supplements (L-carnitine, zinc, astaxanthin, coenzyme Q10, vitamin C, vitamin B12, and vitamin E) and a Chinese herbal medicine, hochu-ekki-to (HE). Serum endocrinological profiles and semen parameters, especially total motile sperm count, were compared between before and after 12 weeks of treatment in both groups. RESULTS: In the supplement group, endocrinological findings were not significantly improved. The semen parameters of semen volume, sperm concentration, and sperm motility were not statistically significantly improved, whereas total motile sperm count was significantly improved. In contrast, none of the endocrinological factors or semen findings were significantly improved by the Chinese herbal medicine although semen concentration, semen motility, and total motile sperm count showed a tendency to increase. CONCLUSION: Because combination antioxidant therapy could improve sperm motility significantly for patients with idiopathic oligoasthenozoospermia, our supplement could be one treatment option for idiopathic male infertility.

[A Case of Ipsilateral Multifocal Renal Cell Carcinoma Treated with Robot-Assisted Partial Nephrectomy].

A 55-year-old male was referred to our hospital for left lower back pain. Computer tomography suggested a left ureteral stone and two left renal tumors at ventral and lateral sites. The ventral tumor measured 7 mm, and it showed intense early enhancement. On the other hand, the lateral tumor measured 22 mm, and it was enhanced weakly. We performed a single-stage robot-assisted partial nephrectomy, because he had chronic renal insufficiency and the two tumors appeared to be different types of renal cell carcinoma. Pathological examination revealed the ventral tumor was clear cell renal cell carcinoma, while the lateral tumor was papillary renal cell carcinoma. He is free of recurrence 1 year and 2 months after operation.

Results of weekday-on and weekend-off administration schedule of sunitinib therapy for advanced renal cell carcinoma.

BACKGROUND: Sunitinib is widely prescribed as first-line therapy for metastatic renal cell carcinoma. To reduce the ratio of severe adverse events and improve the relative dose intensity, we prospectively tried our own alternative medication schedule, which we called the "weekday-on and weekend-off regimen". Here we report the results of this regimen compared to the conventional medication schedule. METHODS: In total, 58 patients were enrolled in this study. Twenty patients were treated under the alternative schedule (group I: weekday-on and weekend-off regimen) and 38 patients were treated using the conventional schedule (group II: 4 weeks on and 2 weeks off regimen). The relative dose intensity (6W-RDI) and prognoses were compared between the two groups. RESULTS: Median 6W-RDI of all the patients was 75.0%. Group I patients demonstrated significantly higher 6W-RDI compared to group II (77.2 vs. 70.4%) (p = 0.019). Multivariate analysis showed that the alternative sunitinib administration schedule was significantly associated with maintaining 6W-RDI above 75% for RCC patients treated with sunitinib (OR 3.592, 95% CI 1.042-12.383, p = 0.043). On the other hand, there were no significant differences between 2 groups regarding occurrence rate of severe adverse events and prognosis by multivariate analysis. CONCLUSIONS: We report the results of an alternative medication schedule, the "weekday-on and weekend-off regimen", as a means of increasing 6W-RDI for metastatic RCC patients.

[A Case of Retroperitoneal Primary Castleman's Disease which was Difficult to Differentiate from Liposarcoma].

A 38-year-old man had a right lower retroperitoneal mass found by abdominal echography in a medical examination, and he consulted the internal medicine of Sumitomo Hospital. On the suspicion of malignant lymphoma, he received a laparotomy with biopsy. Pathological examination revealed that the tumor was either benign lymphadenopathy or low-grade malignant lymphoma, and he was follow-up. Two years later, he was introduced to our department because the follow-up computed tomography revealed signs of a tumor and a mass of adjunctive adipose tissue that increased markedly. Thus, we suspected that the tumor was liposarcoma before the operation, and performed retroperitoneal tumor resection. However, we found that the tumor was pathologically a hyaline vascular type of Castleman's disease and the pathological examination showed no malignant cells in the peritumoral adipose tissue. Since Castleman's disease lacks the characteristic symptoms or image findings, the preoperative diagnosis is generally difficult. Cases with growth of the peritumoral adipose tissue are rare, and the differentiation from the liposarcoma is usually difficult. We discussed how to perform the differential diagnosis of Castleman's disease, and especially about the differential diagnosis of liposarcoma.

[A Case of Androgen Insensivity Syndrome with a Seminoma in the Abdominal Undescended Testis].

A 48-year-old female was referred to our hospital for further urological examination of primary amenorrhea. She had been suffering from amenorrhea since 12 years old. Although she had normal female external genitalia, she had a blind-ended vagina with complete absence of the uterus.Laboratory tests showed high testosterone level and the 46 XY karyotype. Thus, our diagnosis was androgen insensivity syndrome. Magnetic resonance imaging showed bilateral intra-abdominal testes. We performed laparoscopic bilateral gonadalectomy. Pathological diagnosis was seminoma in the right gonad. She is free of recurrence 6 months after operation.

[A Case of Perivascular Epithelioid Cell Tumor (PEComa) of the Uterus Associated with Tuberous Sclerosis Complex Diagnosed by Intra-Abdominal Bleeding from the Uterus].

We report a case of perivascular epithelioid cell tumor (PEComa) of the uterus associated with tuberous sclerosis complex discovered as a result of intraabdominal bleeding. A 54-year-old woman visited the department of obstetrics and gynecology with chief complaints of genital bleeding and abdominal pain lasting three weeks. Abdominal computed tomography (CT) revealed intraabdominal bleeding from the uterine corpus. She had a history of bilateral renal angiomyolipoma, which was treated with partial bilateral nephrectomy at age 25. Moreover, pulmonary lymphangioleiomyomatosis was diagnosed at age 43. Both conditions were detected by the CT scan during this hospitalization. Immediately after the CT scans, the patient entered a state of hemorrhagic shock, and we performed an emergency simple total hysterectomy. Histopathological examination on the resected specimen yielded a diagnosis of uterine perivascular epithelial cell tumor (PEComa). After making a definitive diagnosis of tuberous sclerosis complex (TSC), systemic evaluation was performed. As a result, multiple skin and intracranial lesions characteristic of TSC were identified and we stated administration of everolimus.

[A Case of Urethral Carcinoma in Situ Resected by Urethrectomy of Anterior Urethra].

A 62-year-old man had been treated for urethral stricture developed after his right kidney was harvested for donation to his sister 34 years ago. Transurethral biopsy was performed because of positive urinary cytology and squamous cell carcinoma was detected from the site of urethral stricture. The patient with the desire to preserve the penis was referred to our department. Magneticresonanc e imaging showed no evidence of invasion to subepithelial tissue. Re-biopsy from the site of urethral stricture revealed squamous cell carcinoma in situ. Under the diagnosis of urethral carcinoma cTisN0M0, urethrectomy of anterior urethra with perineal urethrostomy was performed. Histopathological diagnosis was squamous cell carcinoma of the urethra pTis and surgical margins were negative. The patient reported complete urinary continence, normal erections and ejaculation from his urethrostomy. He showed no evidence of recurrence at 28 months after surgery.

Intravesical ATP instillation induces urinary frequency because of activation of bladder afferent nerves without inflammatory changes in mice: A promising model for overactive bladder.

ATP in the suburothelial layer is released from the bladder urothelium by mechanical stimuli. ATP directly activates purinergic receptors that are expressed on primary bladder afferent neurons and induces the micturition reflex. Although ATP is also released to the bladder lumen from the bladder urothelium, the role of ATP in the bladder lumen is unknown. Recently, clinical studies have reported that urinary ATP levels are much higher in patients with an overactive bladder than healthy controls. These results suggest that ATP in the bladder lumen is also involved in the micturition reflex. In this study, we performed intravesical ATP instillation in the mouse bladder. We evaluated urinary function with novel reliable methods using improved cystometry and ultrasonography, which we previously established. We found that intravesical ATP instillation induced urinary frequency because of activation of bladder afferent nerves without inflammatory changes in the bladder or an increase in post-void residual urine. These results suggest that not only ATP in the suburothelial layer, but also ATP in the bladder lumen, are involved in enhancement of the micturition reflex.

Nationwide survey of urological specialists regarding male infertility: results from a 2015 questionnaire in Japan.

Purpose: To investigate the incidence, etiology, treatment indications, and outcomes regarding infertile male patients in Japan. Methods: Between April, 2014 and March, 2015, the authors contacted 47 clinical specialists in male infertility who had been certified by the Japan Society for Reproductive Medicine. The participating clinicians were sent a questionnaire regarding information on their infertile patients, according to etiology and the number and success rates of male infertility operations that had been performed in their practice. Results: Thirty-nine specialists returned the questionnaire and provided information regarding 7268 patients. The etiology of infertility included testicular factors, sexual disorders, and seminal tract obstruction. During the study year, the clinicians performed varicocelectomies, testicular sperm extractions (TESEs), and re-anastomoses of the seminal tract. The rate of successful varicocelectomies was >70%. The sperm retrieval rates with conventional TESE and microdissection TESE were 98.3% and 34.0%, respectively, while the patency rates with vasovasostomy and epididymovasostomy were 81.8% and 61.0%, respectively. Conclusion: Surgical outcomes for infertile male patients are favorable and can be of great clinical benefit for infertile couples. To achieve this, urologists should work in collaboration with gynecological specialists in order to optimize the treatment of both partners.

[Midline Cyst of the Prostate with Increased Urinary Frequency and Urgency : A Case Report].

A 40-year-old man presented to our institution with a few-month history of increased urinary frequency, urgency and voiding difficulty. He had severe lower urinary tract symptoms with an International Prostate Symptom Score of 28 and quality of life score of 6. The mean urinary frequency and voided volume was 20 times per day and 150 ml, respectively. Abdominal ultrasonography and pelvic magnetic resonance imaging revealed the prostate measuring 15 cm3 with a 3 cm midline cyst which compressed the posterior of the bladder wall. A subsequent examination indicated that his lower urinary tract symptoms could be attributed to the cystic mass which mainly affected his storage symptoms. The patient underwent transurethral unroofing of the prostate cyst. Immediately after the surgery, his storage symptoms were improved greatly. The voiding volume was increased to 250 ml, and the frequency of urination was decreased to 8 times. No recurrent symptoms were found for seven months after the surgery.

[A Case of Bilateral Angiomyolipoma Accompanied by Tuberous Sclerosis Complex Successfully Treated with Transcatheter Arterial Embolization Using Functional Kidney Mapping Images Consisting of SPECT-CT and Contrast Enhanced CT Images].

Renal angiomyolipoma (AML) and aneurysm are common in tuberous sclerosis complex (TSC) and represent the main causes of morbidity in adults with TSC. Herein, we report a 22-year-old woman with TSC-associated AMLs and renal aneurysms. She was referred to our hospital for the treatment of multiple renal aneurysms larger than 5 mm in diameter. The previous hospital considered that transcatheter arterial embolization (TAE) of bilateral renal aneurysms would cause deterioration of renal function. To estimate the impact of TAE on renal function, we superimposed contrast enhanced computed tomography (CT) over single-photon emission CT (SPECT)-CT. This fusion image, referred to as functional kidney mapping image, revealed the location of renal arteries and aneurysms, and normal renal parenchyma simultaneously. Functional kidney mapping image was useful to distinguish the AML region from the normal renal parenchyma, and revealed that the planned embolization site was a non-functioning parenchyma. Therefore, TAE for her multiple renal aneurysms was successfully performed without deterioration of her renal function.

[A Case of Adrenal Leiomyosarcoma].

A 61-year-oldman presentedwith a chief complaint of abdominal pain. Enhancedcomputed tomography andmagnetic resonance imaging showeda left adrenal mass with a diameter of 7 cm with heterogeneous enchancement. He was referredto our hospital for further treatment. No endocrinological abnormality was detected. The tumor showed abnormal uptake on fludeoxyglucose positron emission tomography scan. Preoperative diagnosis was left adrenocortical carcinoma (cT2N0M0). Tumor excision was performedandpathological findings on the resectedspecimen revealedleiomyosarcoma of the left adrenal grand. The patient has been followed up for 16 months with no additional treatment. No evidence of local recurrence or metastasis was seen.

[Successful Embolization for Recurrent Varicocele of Testis after Microsurgical Subinguinal Varicocelectomy].

Microscopic subinguinal varicocelectomy has a recurrence of less than 1%, and varicocele recurrence is supposed to be an uncommon post-surgery adverse event. At present, no guidelines exist for the management of recurrent varicoceles after surgery. In this report, we present two cases of post-surgery recurrent varicocele of the testis. Case_1 : A 23-year-old male patient who had undergone microscopic subinguinal varicocelectomy for a grade 3 varicocele was referred to our hospital because of recurrent varicocele. Retrograde venography revealed the persistence of dilated spermatic veins. The former surgeon preserved the dilated vas deferens vein, and this was considered a possible cause of persistence of dilated spermatic veins. The vein considered as vas deferens vein was actually an internal spermatic vein. Case_2 : A 28-year-old male patient complained of recurrence of varicocele two months after the original operation for a grade 3 varicocele. Internal spermatic vessels were slightly visualized on retrograde venography. The possible cause of persistence in this case was insufficient ligation of the internal spermatic vessels. We performed embolization in both cases of recurrent varicocele. Both cases were successfully treated, and there has been no recurrence. Our findings suggest that percutaneous transcatheter embolization of the testicular vein may be effective in the management of postsurgical recurrent varicocele of the testis.