Transvaginal Polytetrafluoroethylene Mesh Surgery for Pelvic Organ Prolapse: One-Year Safety and Efficacy Results.

OBJECTIVE: To evaluate the efficacy and safety of the polytetrafluoroethylene (PTFE) mesh by comparing conventionally used polypropylene (PP) mesh in tension-free vaginal mesh (TVM) surgery for pelvic organ prolapse (POP). METHODS: We conducted an observational cohort study of patients who underwent TVM using a PTFE or PP mesh. PTFE was used from June 2019 to May 2021, and PP mesh from January 2018 to May 2019. Outcomes included POP recurrence, perioperative complications, and patient satisfaction. Restricted mean survival time was used to analyze POP recurrence, comparing the time to recurrence between the two groups at 1year after TVM. RESULTS: Of 171 patients, 104 underwent PP mesh placement (PP group) and 67 underwent PTFE mesh placement (PTFE group). POP recurrence was observed in 10 and nine patients in the PP and PTFE groups, respectively. The mean time until the recurrence in the PTFE group was significantly shorter than that in the PP group (restricted mean survival time difference: -20.3days; 95% CI, -40.1 to -0.5; P = .044). Subgroup analysis revealed the meantime until recurrence was significantly shorter in the PTFE group for postoperative periods 3months or less, ages >70years, and POP stage ≥3. There were no intervention cases in either group and no significant differences in the perioperative complications. Patient satisfaction was greater in the PTFE group after 3months postoperatively. CONCLUSION: TVM surgery with a PTFE mesh is more prone to recurrence than that with a PP mesh, but with higher patient satisfaction. Within 3months of surgery, elderly patients and those with advanced-stage POP require care to prevent recurrence.

Lost Needle During Robot-Assisted Radical Prostatectomy: A Case Report and Literature Review.

Laparoscopic or robotic radical prostatectomy and partial nephrectomy require needle suturing and manipulation. Although uncommon, if a needle is lost during laparoscopy, locating and removing it is challenging. Here, we report a case of needle loss during robot-assisted laparoscopic radical prostatectomy (RARP). A 51-year-old patient with localized prostate cancer underwent RARP. After vesicourethral anastomosis using a 3-0 Barbed Suture with two threads connected in the tail, the two threads were held with a needle holder. One needle was lost during removal through a 12 mm trocar. A thorough laparoscopic examination of the abdominal cavity identified a needle attached to the abdominal wall, which was successfully removed. Needle loss is uncommon, but familiarity with handling and preventing such cases helps surgeons address further deterioration. Stepwise and intensive exploration should be performed to confirm the needle location.

Real-world Outcomes of Tyrosine Kinase Inhibitors Immediately After Immune Checkpoint Inhibitors in Renal Cell Carcinoma.

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have demonstrated a survival benefit for patients with cancer. However, the clinical outcomes of subsequent tyrosine kinase inhibitors (TKIs) after ICI failure in patients with metastatic renal cell carcinoma (mRCC) remain unclear. PATIENTS AND METHODS: We retrospectively examined 38 patients with mRCC who started TKIs immediately after nivolumab with (combination group) or without ipilimumab (nivolumab group) between September 2016 and July 2019. RESULTS: Of the 38 patients, 16 and 11 achieved partial response and stable disease, respectively, resulting in a 42.1% objective response rate and 71.1% disease control rate. The median progression-free survival (PFS) from TKI initiation was 8.8 and 12.9 months in the nivolumab and combination groups, respectively. PFS and overall survival were significantly longer in patients with long-term responses to previous ICI treatment (p=0.0152 and p=0.0155, respectively). CONCLUSION: TKIs demonstrate adequate anti-tumour activity after treatment with ICIs in real-world settings.

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 Prostate Adenocarcinoma Metastasis to the Bilateral Breasts].

A 67-year-old male came to our department with complaints of urinary retention and gross hematuria. The prostate specific antigen (PSA) level in the serum was elevated to 69.5 ng/ml. Thus a transperineal prostate biopsy was performed. The patient was diagnosed with prostate cancer, and lung and bone metastases were also revealed. Treatment for metastatic prostate cancer was performed for approximately 5 years with combined androgen blockade therapy followed by enzalutamide, docetaxel, estramustine, Ra-223 dichloride, estradiol, and then enzalutamide reintroduction. Thereafter, the patient presented with bilateral breast nodules and we referred him to our breast surgery department. Breast needle biopsy findings revealed breast metastasis from prostate cancer, that was not primary breast cancer. The patient underwent a bilateral mastectomy.

The prognostic impact of immune-related adverse events in metastatic renal cell carcinoma patients treated with nivolumab: a real-world multi-institutional retrospective study.

BACKGROUND: Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were correlated with favorable clinical outcome in patients with melanoma. However, in metastatic renal cell carcinoma (mRCC) patients, there have been few reports about the correlation between irAEs and clinical efficacy of anti-programmed cell death protein-1 (PD-1) therapy. METHODS: We retrospectively investigated 160 mRCC patients who started nivolumab monotherapy between September 2016 and July 2019. IrAEs were defined as patients' AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy. We compared the data of patients who received nivolumab into two groups based on the occurrence of irAEs and assessed clinical efficacy in both groups. RESULTS: Of all mRCC patients, 47 patients (29.4%) developed irAEs. In patients who developed irAEs, the objective response rate and disease control rate were 38.8% and 77.6%, which were significantly higher when compared to that in patients without irAEs (p = 0.012 and p < 0.001, respectively). Furthermore, the incidence of irAEs was significantly associated with an increase in progression-free survival (PFS) [Hazard ratio (HR) = 0.4867; p = 0.0006] and overall survival (OS) (HR = 0.526; p = 0.0252). Importantly, PFS and OS seemed to be similar in patients who discontinued treatment because of irAEs and in those who did not discontinue because of irAEs (p = 0.36 and p = 0.35, respectively). CONCLUSION: Development of irAEs strongly correlates with clinical benefit for mRCC patients receiving nivolumab monotherapy in real-world settings.

Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense.

When bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X2 and P2X3 receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6-S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.

[A Case of Metachronous Bilateral Epididymal Tuberculosis after BCG Instillation Therapy].

Beginning in May 2016, an 83-year-old male underwent three transurethral resections for recurrent bladder cancer. In June 2017, following a positive urine cytology exam, a random biopsy of the bladder was performed. The histopathological findings revealed urothelial carcinoma, high grade, pTis. Treatment consisted of bacillus Calmette-Guerin (BCG) instillation. In February 2018, he complained of left scrotal swelling and pain ; and, was diagnosed with left epididymitis. However, based on resistance to the antibiotic agent, epididymal tuberculosis after BCG therapy was suspected and resection of the left testis and epididymis was performed. Histopathological findings revealed epididymal tuberculosis. Three months after the left orchiectomy, the patient complained of right scrotal swelling and pain. Based on antibiotic resistance and the positive findings of a urinary mycobacterium tuberculosis polymerase chain reaction assay, metachronous right epididymal tuberculosis was suspected and the patient underwent resection of the right epididymis. While the histopathological findings did not indicate tuberculosis, the urinary mycobacterium culture was positive. The patient was diagnosed with right epididymal tuberculosis and after surgery was administered an antituberculosis drug.

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.

[TWO CASES OF FALSE POSITIVE 123I-MIBG SCINTIGRAPHY FINDINGS OF UPTAKE IN ADRENAL TUMORS].

Case 1 was a 71-year-old female who had been examined by her primary care physician for palpitation and hypertension. Urinary hormone test results revealed elevated urine metanephrine at 0.20 mg/day, urine normetanephrine at 0.45 mg/day and urine noradrenalin at 234.9 µg/day. 123I-MIBG scintigraphy showed uptake in the right suprarenal area, thus she was referred to our department because of pheochromocytoma. She underwent a laparoscopic right adrenalectomy and pathological results led to a diagnosis of adrenocortical adenoma. Case 2 was a 70-year-old female who had been examined at our hospital for hypertension. Blood hormone test results revealed elevated noradrenalin at 0.70 ng/ml. 123I-MIBG scintigraphy showed uptake in the left suprarenal area and she was referred to our department because of pheochromocytoma. She underwent a laparoscopic left adrenalectomy, thus pathological results showed no tumor lesion.

[A Case of Bilateral Renal Tumors, Renal Cell Carcinoma and IgG4- Related Retroperitoneal Fibrosis].

A 69-year-old man was referred to our hospital for a right renal pelvic tumor noted on a computed tomography (CT) scan at another hospital. Urine cytology was negative. Dynamic CT revealed a right renal pelvic tumor and, accidentally, a small left renal tumor enhanced in the arterial phase and washed out in the venous phase. No defect in the urinary tract was found on retrograde urography, and upper urinary cytology was negative. The patient's level of IgG4 was high, but other tumor markers were negative. We judged the right renal pelvic tumor to be an extrapelvic lesion, probably IgG4-related disease. We temporarily followed up the right renal pelvic tumor but performed retroperitoneal left partial nephrectomy for the small left renal tumor. Histopathology led to a diagnosis of clear cell renal cell carcinoma. Follow-up CT showed no change in the right renal pelvic tumor. We diagnosed the right renal tumor as IgG4-related disease and began steroid administration. After one monthof administration, the IgG4 value and the size of the tumor were reduced.

[Urothelial Carcinoma within a Calyceal Diverticulum Difficult to Distinguish from Cystic Renal Cell Carcinoma].

A 64-year-old man visited our hospital because of right renal cyst and microscopic hematuria which was found in a medical checkup. Contrast computed tomography (CT) and contrast magnetic resonance imaging (MRI) suggested cystic renal cell carcinoma. A laparoscopic nephrectomy was performed, and the surgical specimens showed urothelial carcinoma within the calyceal diverticulum. At a later date, ureterectomy was performed. The surgical specimens had no malignant findings. There has been no recurrence. To our knowledge only 10 cases of urothelial carcinoma within the calyceal diverticulum have beenreported inJapan. A few cases have beenreported overseas.

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.

The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study.

INTRODUCTION: Very little has been elucidated about sexual interest in female-to-male (FtM) transsexual persons. AIMS: To investigate the sexual interest of FtM transsexual persons vs that of men using an eye-tracking system. METHODS: The study included 15 men and 13 FtM transsexual subjects who viewed three sexual videos (clip 1: sexy clothed young woman kissing the region of the male genitals covered by underwear; clip 2: naked actor and actress kissing and touching each other; and clip 3: heterosexual intercourse between a naked actor and actress) in which several regions were designated for eye-gaze analysis in each frame. The designation of each region was not visible to the participants. MAIN OUTCOME MEASURES: Visual attention was measured across each designated region according to gaze duration. RESULTS: For clip 1, there was a statistically significant sex difference in the viewing pattern between men and FtM transsexual subjects. Longest gaze time was for the eyes of the actress in men, whereas it was for non-human regions in FtM transsexual subjects. For clip 2, there also was a statistically significant sex difference. Longest gaze time was for the face of the actress in men, whereas it was for non-human regions in FtM transsexual subjects, and there was a significant difference between regions with longest gaze time. The most apparent difference was in the gaze time for the body of the actor: the percentage of time spent gazing at the body of the actor was 8.35% in FtM transsexual subjects, whereas it was only 0.03% in men. For clip 3, there were no statistically significant differences in viewing patterns between men and FtM transsexual subjects, although longest gaze time was for the face of the actress in men, whereas it was for non-human regions in FtM transsexual subjects. CONCLUSION: We suggest that the characteristics of sexual interest of FtM transsexual persons are not the same as those of biological men. Tsujimura A, Kiuchi H, Soda T, et al. The Pattern of Sexual Interest of Female-to-Male Transsexual Persons With Gender Identity Disorder Does Not Resemble That of Biological Men: An Eye-Tracking Study. Sex Med 2017;5:e169-e174.

[Nonischemic Priapism Following Brachytherapy : A Case Report and a Review].

We report a case of nonischemic priapism following brachytherapy. A 63-year-old man presented 22 days after brachytherapy for prostate cancer. He suffered painless sustained incomplete erection for a few days. The patient was diagnosed with nonischemic priapism by cavernosal blood gas analysis. Right internal pudendal arteriography showed blood pooling in the cavernosum caused by arteriovenous fistula. Selective arterial embolization with gelatin sponge particles was performed and detumescence achieved. To our knowledge,this is the first case of high flow priapism caused by brachytherapy for prostate cancer. In addition,we reviewed the mechanism of high flow priapism.

Authentic role of ATP signaling in micturition reflex.

Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2(-/-) and P2X3(-/-) mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex.

Histologic evaluation of human benign prostatic hyperplasia treated by dutasteride: a study by xenograft model with improved severe combined immunodeficient mice.

OBJECTIVE: To evaluate histologic change in human prostate samples treated with dutasteride and to elucidate direct effects of dutasteride on human prostate tissue, the present study was conducted by using a xenograft model with improved severe combined immunodeficient (super-SCID) mice, although it is well known that dutasteride reduces prostate volume. METHODS: After establishment of a xenograft model of human benign prostatic hyperplasia in morphology and function, samples implanted into super-SCID mice with and without dutasteride were evaluated pathohistologically at 2 and 6 months after initiation of dutasteride administration. RESULTS: The proliferative index evaluated by Ki-67 staining was significantly lower in the dutasteride group than the control at 2 and 6 months after administration. Apoptotic index evaluated by the terminal transferase TdT-mediated dUTP-biotin nick end labeling staining was higher in the dutasteride group than the control at 2 and 6 months after administration. Quick scores in the dutasteride group for staining of both cyclooxygenase-2 (Cox-2) and Ras homolog gene family, member A (RhoA) were significantly lower than those in the control group at 2 and 6 months after administration. CONCLUSION: Dutasteride inhibits cell proliferation and induces apoptosis of prostatic cells, causing a reduced prostate volume. Furthermore, decreased expression of Cox-2 and RhoA within benign prostatic hyperplasia tissue by dutasteride may induce an early effect on improvement of lower urinary tract symptoms, probably by attenuating inflammation reaction of the prostate and decreasing intraurethral pressure, other than the mechanism of reduced prostate volume.

Combination of bladder ultrasonography and novel cystometry method in mice reveals rapid decrease in bladder capacity and compliance in LPS-induced cystitis.

Various animal models have been used in research into bladder dysfunction, and in vivo cystometry is a common method to analyze bladder function in animals. However, it is rather difficult to perform reliably in small animals. Transabdominal bladder ultrasonography combined with cystometry in urethane-anesthetized mice have revealed physical inhibition of bladder wall movement by a bladder catheter conventionally placed in the bladder apex. For reliable evaluation of mouse lower urinary tract function, we established a novel cystometry method in which a catheter was placed in the bladder anterior wall, in combination with bladder ultrasonography. This new method allowed the bladder to be well distended (i.e., larger maximum bladder capacity, lower pressure threshold, higher voided volume, and higher bladder compliance compared with conventional methods), which reflected more spontaneous voiding than conventional cystometry methods. We also demonstrated the usefulness of bladder ultrasonography for analysis of mouse bladder function, especially bladder dynamics, maximum bladder capacity, and post-voiding residual volume. We analyzed bladder functional changes in lipopolysaccharide (LPS)-induced cystitis by combining bladder ultrasonography and this new cystometry method. Bladder ultrasonography revealed a rapid decrease in bladder capacity, and cystometry showed a rapid decrease in voided volume due to intravesical LPS instillation. This new cystometry method also revealed a rapid decrease in bladder compliance caused by LPS instillation, which was not detectable by conventional methods. The combination of ultrasonography and the new cystometry method may become a powerful tool for analysis of mouse bladder function and could contribute to the development of new treatments for bladder dysfunction.

Sexual life of Japanese patients with erectile dysfunction taking phosphodiesterase type 5 inhibitors: an Internet survey using the Psychological and Interpersonal Relationship Scales-Short Form questionnaire.

OBJECTIVES: To investigate details of sexual function of erectile dysfunction in Japanese patients taking phosphodiesterase type 5 inhibitors. METHODS: A Japanese version of the Psychological and Interpersonal Relationship Scales-Short Form was used to carry out a nationwide survey using the Internet. A total of 556 erectile dysfunction patients (age 30-70 years) who had been prescribed a phosphodiesterase type 5 inhibitor and had attempted sexual intercourse within the past 6 months were included in this survey. Scores were compared in relation to the phosphodiesterase type 5 inhibitors most frequently taken within the past 6 months. RESULTS: In the subdomains of self-confidence and spontaneity of the Psychological and Interpersonal Relationship Scales-Short Form, scores for vardenafil and tadalafil were significantly higher than those for sildenafil. In the subdomain of time concern of the Psychological and Interpersonal Relationship Scales-Short Form, the score for tadalafil was significantly lower than that for others. CONCLUSIONS: Our findings support the hypothesis that Japanese patients with erectile dysfunction have high sexual self-confidence, spontaneity and low time concerns when taking tadalafil. These characteristics of tadalafil could be associated with high patient satisfaction and high preference.

[Case of prostate cancer associated with bisphosphonate-related osteonecrosis of the jaw followed by retropharyngeal abscess].

A 67-year-old man with castration-resistant prostate cancer associated with multiple bone metastases had been treated with zoledronic acid and docetaxel. Although there was no evidence of damage around the right lower jaw bone, the patient complained of pain in May 2011, which worsened during the next 2 weeks and was followed by difficulty with breathing. Computed tomographic (CT) findings of the cervical area showed swelling of the cervical tissue with air and tightening of the trachea, suggesting cellulitis caused by gas gangrene. He was intubated and treated with antibiotics. On the 12th hospital day, CT scan revealed a pharyngeal abscess and we performed a drainage operation. On the 20th hospital day, bone of the intraoral lower jaw was exposed, revealing that the infection was caused by osteonecrosis. Additional CT findings showed the abscess extending to the mediastinum and multiple liver metastases. Although antibiotic therapy was continued, the patient died of liver failure on the 61st day.