Add-on anticholinergic therapy for residual nocturia in patients with lower urinary tract symptoms receiving α1-blocker treatment: a multi-centre, prospective, randomised study.

PURPOSE: To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria. MATERIALS AND METHODS: This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume. RESULTS AND LIMITATIONS: Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, -0.6 ± 0.9 in IM twice/day, and -0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged. CONCLUSIONS: A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.

[A CASE OF RIGHT PYONEPHROSIS DUE TO URETERAL STONES IN A HEMODIALYSIS PATIENT].

We report a case of a 64-year-old male with right pyonephrosis due to ureteral stones in association with chronic renal failure. The patient had been treated with hemodialysis for fourteen years. He was admitted to the Department of Internal Medicine of Kurobe City Hospital with chief complaints of fever and lumbago in January 2013. CT demonstrated a right pyonephrosis accompanied by right ureteral stones positioned in the middle and lower ureter. The stones could not be detected by KUB. He was consequently referred to the Department of Urology. Firstly, percutaneous nephrostomy for the right kidney was performed, and 200 ml of pyuria was discharged at that time. Urine culture demonstrated Escherichia coli. Secondly, rigid transurethral ureterolithotripsy (TUL) for the right ureteral stones was performed using Lithoclast, and a ureteral stent was indwelled on day 15 after nephrostomy construction. The nephrostomy catheter and ureteral stent were removed 10 and 21 days after the operation, respectively. The constituents of the stone were CaOx (26%) and CaP (74%). Right hydronephrosis improved and the patient showed no pyelonephritis for 1 year postoperatively.

Factors influencing patient satisfaction with antimuscarinic treatment of overactive bladder syndrome: results of a real-life clinical study.

OBJECTIVES: To investigate patient satisfaction with antimuscarinic treatment of overactive bladder syndrome, and to identify factors having a significant influence on satisfaction. METHODS: A cross-sectional questionnaire survey was carried out to assess treatment satisfaction among male and female patients with overactive bladder (age ≥20 years) in the Hokuriku district of Japan. The overactive bladder symptom scores, treatment efficacies, adverse events (dry mouth and constipation), and patient satisfaction scores were investigated and compared among patients using different antimuscarinic therapeutics. RESULTS: In total, 977 survey respondents (52.6% men; mean age 73.6 years) received antimuscarinic treatment. The mean overactive bladder symptom score of these patients was 6.17; in addition, 32.3% patients were satisfied with their treatment, but 33.1% were dissatisfied. Factors having a significant influence on treatment satisfaction were sex (men were less satisfied), efficacy, adverse events and the overactive bladder symptom score. Constipation negatively influenced patient satisfaction to a greater extent than did dry mouth. Patient satisfaction varied according to the drug used. Constipation was less severe with the immediate-release-type agents (imidafenacin and oxybutynin) than with the extended-release-type (propiverine, solifenacin or tolterodine). CONCLUSIONS: Just one-third of Japanese Hokuriku patients with overactive bladder seem to be satisfied with their antimuscarinic treatment. Patient satisfaction is impaired by poor efficacy and the presence of adverse events; furthermore, constipation should be recognized as an adverse event that negatively influences patient satisfaction to a greater extent than dry mouth. Patient satisfaction differs according to the antimuscarinic agent used, with higher patient satisfaction being associated with less severe constipation.

Clinical factors associated with sperm DNA fragmentation in male patients with infertility.

OBJECTIVE: The clinical factors associated with sperm DNA fragmentation (SDF) were investigated in male patients with infertility. MATERIALS AND METHODS: Fifty-four ejaculates from infertile Japanese males were used. Thirty-three and twenty-one were from the patients with varicoceles and idiopathic causes of infertility, respectively. We performed blood tests, including the serum sex hormone levels, and conventional and computer-assisted semen analyses. The sperm nuclear vacuolization (SNV) was evaluated using a high-magnification microscope. The SDF was evaluated using the sperm chromatin dispersion test (SCDt) to determine the SDF index (SDFI). The SDFI was compared with semen parameters and other clinical variables, including lifestyle factors. RESULTS: The SDFI was 41.3 ± 22.2% (mean ± standard deviation) and did not depend on the cause of infertility. Chronic alcohol use increased the SDFI to 49.6 ± 23.3% compared with 33.9 ± 18.0% in nondrinkers. The SDFI was related to adverse conventional semen parameters and sperm motion characteristics and correlated with the serum FSH level. The SNV showed a tendency to increase with the SDFI. The multivariate analysis revealed that the sperm progressive motility and chronic alcohol use were significant predictors of the SDF. CONCLUSION: The SCDt should be offered to chronic alcohol users and those with decreased sperm progressive motility.

Sperm nuclear vacuoles in relation to acrosome reactions and sperm motility.

We investigated sperm nuclear vacuolation in relation to acrosome reactions and the maintenance of sperm motility. Thirty male patients who visited our Male Infertility Clinic were enrolled. These patients underwent conventional semen analyses, Acrobeads tests, and high-magnification observation of the sperm head to evaluate the degree of nuclear vacuolation on the Acrobeads test scoring after 24 hours of incubation. The presence of acrosome reactions was evaluated using the Acrobeads test. The spermatozoa were classified into three groups: (I) those bound to MH61-beads, (II) motile spermatozoa that did not bind to MH61-beads, and (III) immotile spermatozoa that did not bind to MH61-beads. The percentage of spermatozoa with large nuclear vacuoles (%LNV) was compared between the three groups. The degree of sperm nuclear vacuolation was evaluated in 17,992 ejaculated spermatozoa. The mean %LNVs were 2.4% in group I, 5.8% in group II, and 9.8% in group III. These values were significantly different from each other (P < 0.001, paired t-test). There were no correlations between the %LNV values and the Acrobeads scores. In conclusion, the degree of sperm nuclear vacuolation was significantly lower in the acrosome-reacted spermatozoa and spermatozoa with maintained motility, and higher in the immotile spermatozoa that did not bind to MH61-beads.

Observation of spermatozoa by a high-magnification microscope.

Semen analyses are the primary tool for evaluating male infertility, as semen parameters are useful for predicting potential fertility. In the field of assisted reproductive technology (ART), the single best motile spermatozoon should be selected, especially when performing intracytoplasmic sperm injection (ICSI). In this context, the motile sperm organelle morphology examination (MSOME) was developed as a method of assessing the detailed morphology of motile spermatozoa in real time at a magnification of up to 6,300× on a video system. The use of ICSI with MSOME-selected sperm is called intracytoplasmic morphologically selected sperm injection (IMSI). IMSI improves the outcomes of ICSI. MSOME can be also applied to evaluate male infertility. Among MSOME parameters, the presence of sperm nuclear vacuoles is the most important finding. Large sperm nuclear vacuoles (LNV) are related not only to poor ART outcomes, but also to poor semen quality and sperm DNA damage, such as DNA fragmentation and chromatin condensation failure. It has been suggested that sperm head vacuoles are produced at earlier stages of sperm maturation. It is possible that the number of LNV can be decreased by surgical or medical treatment for male infertility. Therefore, the level of LNV has the potential to be used as an alternative parameter of semen quality and a new tool for evaluating the therapeutic effects of treatment in male patients with infertility.

Efficacy of DynaCT for surgical navigation during complex laparoscopic surgery: an initial experience.

BACKGROUND: Precise understanding of surgical anatomy is required during complex laparoscopic surgery (CLS). The purpose of this study was to present our initial operative experience with CLS facilitated by surgical navigation through DynaCT technology. METHODS: Intraoperative computed tomography (CT) images of two CLS cases were obtained by a C-arm DynaCT system (Artis Zeego, Siemens Healthcare, Erlangen, Germany). Image reconstruction was performed on a workstation to define particular anatomical structures of the target tumor. The reconstructed CT images were repeatedly displayed on a submonitor. The surgeon then compared the CT images with a laparoscopic image of the surgical field, thus providing a virtual map to the surgeon. RESULTS: Using the near-real-time surgical navigation system, the surgeon could visualize the surgical anatomy and easily perform the CLS. All procedures were performed successfully with a satisfactory diagnostic yield. CONCLUSION: This novel technology has great potential for application in CLS because it enables generation of accurate depictions of small target tumors and increases the surgeon's confidence during the procedure.

Efficacy of laparoendoscopic single-site biopsy for diagnosis of retroperitoneal tumor of unknown origin.

BACKGROUND AND PURPOSE: When percutaneous image-guided biopsies are not possible for retroperitoneal tumor of unknown origin (RTUO), surgical tissue diagnosis becomes necessary. Laparotomy and laparoscopic surgery are current standard treatments; however, the laparoendoscopic single-site (LESS) approach offers many potential benefits. We describe our technique for LESS biopsy of RTUO. PATIENTS AND METHODS: Five patients underwent LESS biopsy for diagnosis of RTUO. A multichannel port was inserted into the peritoneal or retroperitoneal space through a 3-cm skin incision, which adequately exposed the retroperitoneal tumor. The specimen was grasped and isolated circumferentially from the surrounding tissue. RESULTS: LESS surgery was performed successfully without any complications such as open conversion. Mean operative time was 183 min and estimated blood loss was negligible. The diagnoses were IgG4-related retroperitoneal fibrosis (n = 4) and lymphoma (n = 1). Sufficient specimens were safely obtained not only for pathological diagnosis but also for further examinations such as immunophenotyping or DNA analysis. Convalescence was satisfactory. All patients were treated appropriately according to the resulting diagnosis. CONCLUSIONS: LESS biopsy for RTUO is a safe and effective alternative to open surgical and standard laparoscopic biopsies. Further studies of clinical experiences are needed to confirm the benefits of this new technique.

Early quality of life outcomes in patients with prostate cancer managed by high-dose-rate brachytherapy as monotherapy.

OBJECTIVES: To evaluate the early quality of life outcomes in prostate cancer patients managed by high-dose-rate brachytherapy as monotherapy. METHODS: A total of 51 patients with cT1c-T3aN0M0 prostate cancer treated between July 2007 and January 2010 were included in this study. The average age was 69 years, and the average initial serum prostate-specific antigen was 10.98 ng/mL. A total of 25, 18 and eight patients were considered to be low, intermediate and high risk, respectively. All patients received one implant of Ir-192 and seven fractions of 6.5 Gy within 3.5 days for a total prescribed dose of 45.5 Gy. For high-risk prostate cancer, neoadjuvant androgen deprivation therapy was carried out for at least 6 months, and continued after high-dose-rate brachytherapy. Quality of life outcomes were measured by using the International Prostate Symptom Score, the Functional Assessment of Cancer Therapy-Prostate and the International Index of Erectile Function Questionnaire. The oncological outcome was assessed by serum prostate-specific antigen and diagnostic imaging. Adverse events were also recorded. RESULTS: The Functional Assessment of Cancer Therapy-Prostate scores decreased for a few months after high-dose-rate brachytherapy, and recovered to pretreatment condition thereafter. The International Prostate Symptom Score significantly increased 2 weeks after treatment for each of its items and their sum, and it returned to baseline after 12 weeks. Sexual function decreased at 2 and 4 weeks, and recovered after 12 weeks. Severe complications were rare. Within a median follow up of 17.2 months, two patients showed a prostate-specific antigen recurrence. CONCLUSIONS: High-dose-rate brachytherapy for prostate cancer is a feasible treatment modality with acceptable toxicity and only a limited impact on the quality of life.

Laparoendoscopic single-site surgery for partial nephrectomy without ischemia using a microwave tissue coagulator.

BACKGROUND: Herein, we report our initial experience with laparoendoscopic single-site surgery for partial nephrectomy (LESSPN) using a microwave tissue coagulator (MTC). METHODS: Two patients with small and exophytic renal tumors underwent LESSPN. A multichannel port was inserted into the peritoneal or retroperitoneal space through a 3-cm skin incision. After tumor exposure, the surgeon introduced a laparoscopic MTC instrument through a 5-mm port and the tumor margin was coagulated circumferentially. After coagulation, the tumor was resected without renal pedicle clamping. RESULTS: These procedures were successfully performed without any conversions to standard laparoscopy or need for placement of additional trocars. The operative times were 183 and 160 minutes, respectively. The estimated blood loss was <150 mL in both cases. The final length of the LESS wound was 3 cm. Using the transumbilical approach, the operative scar receded into the umbilicus and was hardly visible. CONCLUSIONS: This novel surgical technique is feasible and enables the bloodless resection of a renal tumor without renal pedicle clamping. Further clinical experience and longer follow-up are needed to define the benefits of this new technique.

[A case of urachal abscess accompanied by a stone].

A 64-year-old woman presented to our hospital with the chief complaints of abdominal pain and appetite loss, and she was admitted to the internal medicine department. Kidney, ureter and bladder X-ray revealed intrapelvic calcification near the bladder, and so, the patient consulted our department. Computed tomography and magnetic resonance imaging revealed an urachal abscess accompanied by a stone. Open surgery was performed under general anesthesia. The mass adhered tightly to the intestine and bladder. The urachal abscess ruptured during the operation, and pus leaked into the intraabdominal cavity. Partial cystectomy was performed to remove the mass completely. The stone existed in the urachal abscess, and its constituents were CaOxa (51%) and CaP (49%). The pathological diagnosis was urachal abscess without malignancy.

[Case of heterochronous triple urogenital cancer (renal cell carcinoma, bladder cancer, prostatic cancer)].

We report a case of a 73-year-old male with heterochronous triple urogenital cancer. The patient was referred to our hospital because serum PSA was elevated (7.0 ng/ml) in 1998. Prostatic needle biopsy revealed prostatic cancer in the right lobe, and total prostatectomy was performed. The histopathological diagnosis was moderately differentiated adenocarcinoma (TlcNOMO). Non-muscle invasive bladder cancer (NMIBC) was detected during an examination for microhematuria in 2002. Transurethral resection of the bladder tumor (TURBT) procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). A right renal mass was detected incidentally on follow-up CT for bladder cancer in 2008. Renal enucleation was performed in 2009. The histopathological diagnosis was grade 2 clear cell renal cell carcinoma (pTlaNXMO). NMIBC was detected on follow-up urethrocystoscopy in 2011. The TURBT procedure was performed, and the histopathological diagnosis was grade 2 urothelial carcinoma (pTa). On follow-up for urogenital cancer patients, it is important to investigate recurrence of the primary cancer and also heterochronous canceration of other urogenital organs.

Laparoscopic radical nephrectomy under near real-time three-dimensional surgical navigation with C-arm cone beam computed tomography.

OBJECTIVE: The aim of this study was to demonstrate the advantages of C-arm cone beam computed tomography for imaging guidance of laparoscopic radical nephrectomy (LRN). METHODS: Four patients referred to the authors' institution for LRN were included in this study. To visualize the renal vascular anatomy, the Iopamiron 300 contrast agent was injected intravenously. The surgeon could adjust the viewing angle of the images and rotate the reconstructed three-dimensional (3D) image manually by using a mouse-like controller. Using the near real-time 3D navigation images, the surgeon was able to recognize the renal vascular anatomy, and more easily perform the LRN. RESULTS: All procedures were successfully performed with a satisfactory diagnostic yield or therapeutic effect without procedure-related complications. CONCLUSION: This novel technology has great potential for application in LRN because it enables accurate depiction of the renal vessels and increases surgeon confidence.

Testicular volume discrepancy is associated with decreased semen quality in infertile Japanese males with varicoceles.

Purpose: We retrospectively reviewed infertile Japanese males for testicular volume discrepancies (D) and semen parameters to evaluate whether left grade II-III varicoceles (V) cause testicular damage. Methods: Seventy-seven patients who had idiopathic male infertility and 88 who had V without other causes of infertility were examined. We excluded cases of azoospermia. Testicular volume was measured using a punched-out orchidometer. D was defined as a size difference of at least 3 ml. The frequency of D was compared between the patients with and without V. The semen parameters were reviewed in association with D and V. Results: The mean left and right testicular volumes were 19.4 and 20.1 ml, respectively (p < 0.001). D with a smaller left testis was more common in V+ cases than in V- cases (26.1 vs. 13.0%, p = 0.0351). The sperm count and motility were also significantly lower (p = 0.0213 and p = 0.0217, respectively) in the D+ patients with a smaller left testicular volume. Conclusions: In the patients with V, D was more common than in those without V. The semen parameters were worse if D was present in the patients with V. These results indicated that V could induce testicular atrophy and negatively affect semen quality. Therefore, the ipsilateral reduced testicular volume is considered to be a sign of persisting testicular damage by V.

Severe oligozoospermia in a patient with myxedema coma.

A case of severe oligozoospermia with myxedema coma is herein presented. The patient was referred to a male infertility clinic with a 5-year history of primary infertility. Decreased serum testosterone and elevated serum prolactin without abnormal MRI findings in the hypothalamus, and decreased semen volume and sperm motility were noted. A GnRH test revealed a decreased luteinizing hormone response, whereas the HCG test showed a normal testosterone increase. Because a urinalysis after ejaculation indicated retrograde ejaculation, imipramine administration was started. However, the semen quality deteriorated, so the patient was referred to an ART clinic. Twenty-one months from the initial visit, the patient developed a loss of consciousness and edema due to myxedema coma, a life-threatening state of hypothyroidism. The patient recovered after 1 month of thyroid hormone replacement therapy (HRT) with corticosteroids. Three months after the myxedema coma, a semen analysis showed a decreased semen volume (0.2 mL) and severe oligozoospermia (two spermatozoa/ejaculate). Elevated prolactin and decreased testosterone levels were still present. These parameters gradually improved after restoration of euthyroidism by HRT. In conclusion, physicians should confirm the thyroid function in the management of male infertility, especially in patients with elevated prolactin levels.

PACAP-mediated sperm-cumulus cell interaction promotes fertilization.

The developing acrosome in spermatids contains pituitary adenylate cyclase-activating polypeptide (PACAP). However, the role of the acrosomal PACAP remains unclear because it has not been detected in mature spermatids and sperm. We reinvestigated whether the sperm acrosome contains PACAP. An antiserum produced against PACAP reacted to the anterior acrosome in epididymal sperm fixed under mild conditions, suggesting that PACAP acts on oocytes and/or cumulus cells at the site of fertilization. Immunolabeling and RT-PCR demonstrated the presence of PACAP type I receptor, a PACAP-specific receptor, in postovulatory cumulus cells. To investigate the role of PACAP in fertilization, we pretreated cumulus-oocyte complexes with the polypeptide. At a low concentration of sperm, the fertilization rate was significantly enhanced by PACAP in a dose-dependent manner. Sperm penetration through the oocyte investment, cumulus layer, and zona pellucida was also enhanced by PACAP. The enhancement was probably due to an enhancement in sperm motility and the zona-induced acrosome reaction, which were stimulated by a cumulus cell-releasing factor. Indeed, PACAP treatment increased the secretion of progesterone from the cumulus-oocyte complexes. These results strongly suggest that in response to PACAP, cumulus cells release a soluble factor that probably stimulates sperm motility and the acrosome reaction, thereby promoting fertilization.

Hematospermia: etiology, diagnosis, and treatment.

Hematospermia is a relatively frequent, distressing, and frightening symptom for the majority of men. Although the differential diagnosis list is extensive, it is usually a benign, self-limiting disorder, including inflammatory and infective pathologies, resolving in several weeks. However, in some cases, hematospermia is the harbinger of more serious pathological lesions that should not be missed. In younger patients below 40 years of age, infection of the urogenital tract is the most common etiology. Simple routine laboratory studies should identify the pathological factors. In patients 40 years or older, or those with persistent or recurrent conditions or associated symptoms, it is necessary to exclude urogenital malignant disorders. Patients should also undergo medical history taking, physical examination including temperature and blood pressure assessment, digital rectal palpation, and laboratory blood, urine, and semen tests. If the diagnosis is still unclear, further investigations involve transrectal ultrasonography, magnetic resonance imaging, urethrocystoscopy, and histological confirmation by biopsy. Treatment for hematospermia depends on the underlying pathological lesions, but often involves only minimal examinations and simple reassurance in most cases. Hematospermia caused by genitourinary infections is effectively treated with appropriate antiviral, antibiotic, or antiparasitic agents. Hematospermia due to malignant disorders including prostate, testis, and seminal vesicle cancers resolves with definitive treatment of the primary lesions.

[A case of a foreign body (sheath dilator) in the urethra and bladder].

An 84-year-old man presented with the chief complaints of fever and disturbance of consciousness at another hospital. A sheath dilator had been inserted into the urethra instead of an indwelling catheter at the hospital. Since he had previously been treated for myelodysplastic syndrome in our Department of Internal Medicine, he was transferred to our hospital. He presented at our Department with the chief complaints of urinary difficulty and lower abdominal fullness. Kidney-ureter-bladder x-ray and computed tomography revealed the sheath dilator in the uretha and bladder. First, we performed a percutaneous cystostomy under local anesthesia. Second, we utilized optical forceps and successfully removed the sheath dilator transurethrally under intravenous anesthesia.

[Successful interferon-alpha therapy of renal cell carcinoma with lung metastasis: a case report].

A 67-year-old man was admitted with a chief complaint of dyspnea. Computed tomography (CT) revealed a left renal tumor, 12 cm in diameter, with tumor thrombus in the left renal vein, multiple lung metastases, right pleural effusion, and para-aortic lymph node metastases. Because of poor condition in respiratory status, nephrectomy was considered to be impossible and the patient was administered 6×106 IU of interferon-alpha daily. Then, 6×106 IU was also administered three times a week. At 14 months after interferon-alpha therapy, CT scan showed complete remission of lung, pleura metastases and right pleural effusion, and the left renal tumor was markedly reduced in size. Because of improvement of general condition, nephrectomy of the left kidney was performed. Twenty-seven months after the start of interferon-alpha therapy, the patient is alive without evidence of disease.

Effects of eicosapentaenoic acid on biochemical failure after radical prostatectomy for prostate cancer.

AIM: To study the effects of eicosapentaenoic acid (EPA) on prostate-specific antigen (PSA) failure in prostate cancer patients who underwent prostatectomy. PATIENTS AND METHODS: Sixty-two prostate cancer patients whose PSA levels were less than 0.2 ng/ml 3 months after surgery were randomized to either an EPA group (n=32) or a control group (n=30). EPA (2.4 g/day) was administered in the EPA group for 2 years. PSA was measured every two months. RESULTS: The EPA concentration increased but the docosahexaenoic acid concentration decreased significantly (P<0.001) in erythrocytes. The PSA recurrence rates during a mean follow-up of 53.8 months were not different between the two groups (p=0.16). CONCLUSION: A longer and/or larger intervention or docosahexaenoic acid supplementation might be necessary to identify significant preventive effects of mega-3 polyunsaturated fatty acids on PSA recurrence.