Utilization rate and long-term persistence of combination pharmacotherapy with ß3-agonists and antimuscarinics for overactive bladder refractory to monotherapy in a real-world setting.

AIM: To assess real-world treatment profiles, including utilization rate, time to and reasons for discontinuation of combination pharmacotherapy with ß3 -agonists and antimuscarinics for refractory overactive bladder (OAB) through a retrospective chart review. METHODS: We retrospectively reviewed the records of OAB patients who received ß3 -agonists or antimuscarinics at our hospital between 2012 and 2020 and analyzed the clinical course of patients who progressed to combination therapy. Data on age, sex, major complaints, OAB symptom score at the initiation of combination therapy, treatment persistence, and reasons for discontinuation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and persistence rate at 12 months. RESULTS: Of the 2163 patients receiving ß3 -agonists or antimuscarinics, only 84 (3.8%) progressed to combination therapy with both drug classes. At therapy initiation, most (98%) of these patients had moderate to severe OAB symptoms. Median treatment duration and 12-month persistence rate for combination therapy were 595 days and 64.0%, respectively. The reasons for discontinuation were insufficient treatment efficacy followed by adverse effects including voiding impairment in nearly 10% of the patients. None of the baseline parameters was independently associated with persistence in the multivariate analysis. CONCLUSION: While underutilized among OAB patients refractory to monotherapy, combination pharmacotherapy showed a greater persistence rate than published mirabegron or antimuscarinic monotherapy when applied to patients with moderate to severe symptoms. Treatment-emergent voiding impairment is a concern associated with this mode of therapy. A small sample size at a single institution is the limitation of this study.

Overactive bladder medication: Persistence, drug switching, and reinitiation.

AIM: To assess real-world treatment profiles, including the time to and reasons for discontinuation or drug switching, treatment reinitiation, and postdiscontinuation follow-up in patients receiving antimuscarinics or ß3-agonists for overactive bladder (OAB) through a retrospective chart review. METHODS: We retrospectively reviewed medical charts of 777 patients, aged ≥18 years, who underwent antimuscarinic or ß3-agonist therapy at our hospital. Data on patient's age, sex, chief complaint, and OAB symptom score at therapy initiation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and the persistence rate at 12 months. RESULTS: Older patients, male patients, and those with more severe urgency symptoms were more likely to show treatment persistence with OAB medications. Treatment persistence with mirabegron was significantly longer than that with antimuscarinics when administered as either the first- or second-line medication. Multivariate analyses showed that urgency severity and use of mirabegron were independently associated with better persistence (p = .026 and p = .018, respectively). Out of 583 patients who discontinued medication, 344 continued with the visit schedule, and the reinitiation rate of the OAB medication was 19% at a median follow-up of 24 months. CONCLUSION: Although the persistence rates for OAB medications improved with the introduction of mirabegron, most patients still discontinued the medication therapy within 1 year. The treatment strategies for patients with mild symptoms and those who are resistant to medication can still be improved. Tailored individualized treatments that avoid excessive reliance on pharmacotherapy would be key to further improve treatment outcomes in OAB patients.

Bowel perforation by a peritoneal dialysis catheter: report of two cases.

BACKGROUND: Complications of peritoneal dialysis (PD) such as pain and catheter leakage are frequently reported. Delayed bowel perforation of a PD catheter is a rare adverse event but a serious complication associated with significant mortality. Bowel perforation of a PD catheter is difficult to differentiate from PD-related peritonitis and likely to result in a delay in diagnosis. Here, we report two cases of bowel perforation after PD catheter insertion by the stepwise initiation of PD using the Moncrief and Popovich technique (SMAP) and peritoneal wall anchor technique (PWAT). CASE PRESENTATION: The first case was a 53-year-old woman with end-stage renal disease (ESRD) due to diabetic nephropathy and a history of entero-adhesiolysis. She underwent PD catheter insertion by the SMAP with PWAT. Four months after PD catheter insertion, the catheter was found to perforate sigmoid colon. The second case was a 57-year-old woman with ESRD due to large polycystic kidney disease. She underwent the same procedure. After exteriorization of the catheter, she developed peritonitis due to perforation of the catheter tip into the bowel. Both patients were safely removed the catheter with uneventful recovery. CONCLUSION: We reported two cases of a rare complication of PD catheter. The SMAP method, PWAT, enlarged kidneys and migration of the lower cuff may be risk factors of bowel perforation of a PD catheter.

[Therapy-Related Acute Myeloid Leukemia Following Etoposide Based Chemotherapy in Germ Cell Tumor].

A 27-year-old man visited our hospital with painless swelling of the left scrotum. Hematologic studies showed the following levels of lactate dehydrogenase, 3,171 IU/l ; alpha-fetoprotein, 2.2 ng/ml ; and ß- human chorionic gonadotropin, 0.4 ng/ml, and abdominal computed tomography revealed a mass of 10×8 ×4 cm in the left testis, and that of 3.5×3.0×5.0 cm in the left renal hilar lymph node, without any other metastasis. Left high inguinal orchiectomy was performed, and histopathological examination revealed mixed form with seminoma and teratoma. He was diagnosed to have a left germ cell tumor with left renal hilar lymph node metastases, pT1, N3, M0, stage II C, indicating poor prognosis with IGCCC. The patient received four cycles of chemotherapy, COMPE regimen (CDDP, VCR, MTX, PEP, VP-16 [etoposide]). After lactate dehydrogenase, alpha-fetoprotein, and ß -human chorionic gonadotropin all normalized, retroperitoneal lymph node dissection was performed. Histopathological examination revealed only a mature teratoma. Two and half years later, hematologic studies showed blast transformation. Bone marrow biopsy revealed acute myeloblastic lymphoma (M2). The patient received one cycle of AraC and daunorubicin, one cycle of high dose AraC, and three cycles of AraC and mitoxantrone. After chemotherapy, he has maintained a disease-free status for 11 years. In this case, etoposide, a topoisomerase II inhibitor, was the presumed cause of therapy-related acute myeloid leukemia. After administering chemotherapeutic agents especially etoposide, it is important to check blood count periodically for a long time.

Baseline factors and surgical procedures affecting changes in lower urinary tract symptoms after robot-assisted radical prostatectomy: the impact of nerve-sparing.

PURPOSE: To determine baseline factors and surgical procedures associated with clinically meaningful improvement or deterioration of lower urinary tract symptoms (LUTS) after robot-assisted radical prostatectomy (RARP). METHODS: We retrospectively reviewed our RARP database and analyzed the changes in the International Prostate Symptom Score (IPSS) at baseline and 1, 3, 6, and 12 months postoperatively. Multivariable ordinal logistic regression analysis was performed to determine variables that predicted clinically meaningful improvement (∆IPSS ≤ -5) or deterioration (∆IPSS ≥ 5) in LUTS after RARP. RESULTS: A total of 172 patients were eligible for analysis. Patients aged ≥ 70 reported a higher IPSS before and after RARP (all p < 0.05). Patients with a prostate volume of > 30 mL or body mass index of < 24 kg/m2 had worse preoperative LUTS; however, the difference disappeared after RARP. While patients with or without nerve-sparing (NS) had a similar preoperative LUTS burden, the NS group reported significantly lower IPSS than the non-NS group at all postoperative time points (p < 0.05). Twelve months after RARP, LUTS improved in 27% and worsened in 6% of patients in the NS group, compared with 20% and 24% of those in the non-NS group, respectively (p = 0.018). Preoperative IPSS (OR, 0.84; 95% CI, 0.79-0.89) and NS (OR, 0.39; 95% CI, 0.18-0.83) were independently associated with clinically meaningful changes of LUTS at 12 months after RARP. CONCLUSION: Other than baseline LUTS severity, NS was the only independent factor associated with clinically meaningful changes in LUTS after RARP.

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

[Heparin as bridging anticoagulant and antiplatelet therapy during the perioperative period].

Anticoagulant and antiplatelet medications are commonly used for the treatment and prevention of cardiovascular diseases. We studied 84 patients who received heparin as a bridging anticoagulant and antiplatelet therapy during the perioperative period. Hospitalization was extended for adjusting anticoagulant and antiplatelet drugs and also bleeding complications in the perioperative period. There were 25 instances of bleeding complications (29.7%) in this study. These complications mainly occurred when anticoagulant and antiplatelet medications were restarted in the postoperative period. In transurethral surgery, patients taking warfarin and antiplatelet drugs (aspirin or ticlopidine) had a statistically significant increase in bleeding complications compared to patients taking warfarin alone. We compared 51 cases of transurethral resection of bladder tumor, transurethral resection of the prostate holium laser enucleation of the prostate, nephroureterectomy and percutaneous nephrolithotomy with heparinization were compared to 692 cases with no heparinization. The heparinization group had a statistically significant longer hospitalization period and an increase in bleeding complications. There was one instance of thromboembolism (1.2%) in our series. This involved stent thrombosis of a patient who had drug-eluting stent in the left anterior descending coronary artery. She died three days postoperatively. The number of patients taking anticoagulant and/or antiplatelet drugs is predicted to increase in the future due to aging of the population. Guidelines for the management of anticoagulant and antiplatelet therapy in the urological period are considered necessary.

[A case of percutaneous nephrolithotripsy for pediatric renal stone].

Urolithiasis in pediatric patients is relatively rare. Extracorporeal shock wave lithotripsy and endoscopic procedures play a major role in treating pediatric urolithiasis. A 3-year-old girl presented with macroscopic hematuria and right back pain and was diagnosed with a right renal stone (15 mm). Obstruction of ureteropelvic junction was suspected on computed tomography-urography and therefore the patient underwent percutaneous nephrolithotripsy (PNL). The operation was performed using a 12 Fr miniature nephroscope and Ho : YAG laser without any complications. This patient achieved a stone-free status. The stone analysis revealed a mixture of calcium oxalate and ammonium acid urate. PNL with a miniature nephroscope is safe and effective treatment for pediatric urolithiasis.

[Long-term outcome of initial treatment with Bacillus Calmette-Guérin for carcinoma in situ of the upper urinary tract].

To assess appropriate treatment strategies for transitional cell carcinoma in situ (CIS) of the upper urinary tract (UUT), we evaluated the long-term outcome of Bacillus Calmette-Guérin (BCG) perfusion therapy for CIS of UUT. We retrospectively reviewed the medical records of 24 patients who underwent BCG perfusion therapy for CIS of UUT between August 1993 and August 2009. Patients received at least one course of BCG (once weekly for 6 weeks). The median follow-up period was 48.5 months (range 16-201 months). In 23 patients (96%), cytology became negative after one course of BCG perfusion and 12 patients (50%) remained disease-free for a median follow-up of 38. 5 months. In 11 patients positive cytology recurred, and in five of them nephroureterectomy was performed after radiologic studies showed the presence of a tumor in the UUT. Histopathology showed invasive tumor (pT3) in all cases, and three of them experienced distant metastases after surgery. In conclusion, BCG perfusion therapy is effective for the treatment of CIS of UUT with long-term follow-up. However, in cases with a poor response or recurrence of CIS, there is a high risk of developing invasive tumor. Surgical intervention should be immediately considered in such cases after the first course of BCG perfusion therapy.

[A case of bilateral renal calculi in a 1-year-old female with adenine phosphoribosyl transferase partial deficiency].

We report a case of bilateral renal calculi in a 1-year-old female with adenine phosphoribosyl transferase (APRT) partial deficiency. She initially visited another institution with high fever as the major complaint. Computed tomography revealed a bilateral renal stone and left hydro nephrosis. In the urine, there were 2, 8-dihydroxyadenine (DHA) crystals. An analysis of the APRT gene revealed the APRT deficiency and the genotype to be APRT*J/APRT*Q0. We performed extracorporeal shock wave lithotripsy (ESWL) under general anesthesia, and as dissolution therapy we administered Meylon through the nephrostomy and citric acid orally. The stone disappeared from her kidney. The analysis of the stone fragments revealed 2,8- dihydroxyadenine (DHA) urolithiasis.

[Case of rectal migratin of mesh after TVM (tension-free vaginal mesh) operation].

A 64-year-old woman presented with recto-cutaneous fistula after tension-free vaginal mesh reconstruction using polypropylene mesh for pelvic organ prolapse. Eleven months after the operation, an ulcerative lesion with stools smell secretion developed in the left hip. Magnetic resonance imaging and colonoscopy revealed a migration of the left arm of the mesh and a recto-cutaneous fistula. The patient underwent excision of the infected mesh and rectal wall closure together with transient colostomy. After 8 months, colonoscopy revealed a new migration of the mesh in the rectum, which was also removed. The colostomy was closed one year later and rectal erosion has not reccurred since then. The possibility of developing a rare but severe mesh-related complication as presented here should always be kept in mind.

Efficacy of nondrug lifestyle measures for the treatment of nocturia.

PURPOSE: Nocturia has a major impact on quality of life and affects numerous aspects of health. Lifestyle modifications are expected to be helpful in improving nocturia. However, the efficacy of this strategy has not been established. We tested the efficacy of nondrug lifestyle measures as a first step in treating nocturia and found factors predictive of the efficacy of the intervention. MATERIALS AND METHODS: We conducted a prospective evaluation of 56 patients treated at 3 hospitals between 2005 and 2009 for symptomatic nocturia. The patients were advised to modify their lifestyle to improve nocturia. Lifestyle modifications consisted of 4 directives of 1) restriction of fluid intake, 2) refraining from excess hours in bed, 3) moderate daily exercise and 4) keeping warm in bed. The frequency volume chart, International Prostate Symptom Score, and Pittsburgh Sleep Quality Index before and 4 weeks after the intervention were used to evaluate the efficacy of the therapy. RESULTS: Mean nocturnal voids and nocturnal urine volume decreased significantly from 3.6 to 2.7 (p <0.0001) and from 923 to 768 ml (p = 0.0005), respectively. Of the 56 patients 26 (53.1%) showed an improvement of more than 1 episode. This treatment was significantly more effective in patients with a larger 24-hour urine production. CONCLUSIONS: Nondrug lifestyle measures were effective in decreasing the number of nocturia episodes and improving patient quality of life. Patients with polyuria showed a better response to the treatment.

[Antimicrobial prophylaxis in radical prostatectomy : single dose versus 1-day treatment].

An adequate protocol for antimicrobial prophylaxis (AMP) in radical prostatectomy (RP) has not been established. We retrospectively compared the occurrence of perioperative infection following RP between two different AMP protocols. This study included 340 cases with prostate cancer who underwent RP at our institution between January 2005 and December 2008. The 1-day group consisting of 93 cases received a second generation cephem, cefotiam, intravenously during and after the operation on the operative day. The single dose group consisting of 247 cases received cefotiam during the operation only. The incidence of surgical site infection (SSI) and remote infection (RI) was retrospectively investigated. There was no significant difference in the rate of SSI and RI occurrence between the 1-day group (2.2, 0%) and single dose group (3.6, 0.4%) (p = 0.52). The single dose protocol of AMP seems sufficient for prevention of perioperative infection in RP.

[Multiple chromophobe renal cell carcinoma: a case report].

A 46-year-old woman with gross hematuria was referred to our hospital with suspicion of bilateral renal cell carcinoma. Computed tomography (CT) showed multiple renal tumors with contrast enhancement and multiple lung nodules. Based on a diagnosis of bilateral multiple renal cell carcinoma with multiple lung metastases, a combination therapy with interferon-alpha (IFN-alpha) and 5-flurouracil (5-FU) was initiated. Six months later, all the renal and pulmonary lesions remained the same, and IFN-alpha alone was continued thereafter. One tumor in the right upper pole decreased in size during the next six years, while all the other lesions remained unchanged. Then the immunotherapy was discontinued on the basis of possibility that the tumors could be benign lesions. Three years later,the right upper renal tumor disappeared on CT, but, one of the left renal tumors showed progressive disease. The patient underwent left partial nephrectomy together with resection of neighboring small tumors. All the excised tumors were diagnosed as chromophobe renal cell carcinoma on histological examination. There has been no change with the remaining tumors for 1.5 years postoperatively.

Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients.

Glutathione S-transferases (GSTs), superoxide dismutase 2 (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase T1 (GSTT1)-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction (PCR). Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. A significantly better response to varicocelectomy was found in patients with the GSTT1-wt genotype (63.2%) and NQO1-Ser/Ser genotype (80.0%) than in those with GSTT1-null genotype (35.3%) and NQO1-Pro/Pro or NQO1-Pro/Ser genotype (45.2%), respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.

[Health-care seeking behavior related to lower urinary tract symptoms : a population-based study in Japan].

We aimed to investigate health-care seeking behavior related to lower urinary tract symptoms (LUTS) using a questionnaire-based survey. The questionnaire included questions related to 5 demographic issues, 9 past histories, 8 LUTS, and others about health-care seeking related to LUTS. We sent the questionnaire to 6,000 residents, 41 to 70 years old, in three Japanese communities (Tobetsu, in a subarctic zone, Kumiyama, in a temperate zone, and Sashiki, in a subtropical zone). Of the questionnaires, 36.5% were valid for analyses. The prevalence of desire for treatment for LUTS was 15.6% (still-treated health-care seeker : 4.5%, never-treated health-care seeker : 11.1%). This finding suggested that, among residents with a desire for treatment, only 29% actually had treatment for LUTS. Multivariate analyses revealed that incomplete emptying, weak stream, and straining for males, and urinary frequency, nocturia, and incontinence for females were independently significant factors associated with health-care seeking related toLUTS.

[Sperm cryopreservation for cancer patients: 5-year experience in a private hospital in Japan].

Private hospitals in Japan appear to play an important role in the fertility preservation in cancer patients. However, only a few university-related institutions have published their data about sperm banking. Here we report our experience in a private hospital. The database of 5 years of experience with sperm cryopreservation for male cancer patients was reviewed. We assessed the type of cancer, timing of collection, sperm quality, and utilization for reproductive purposes. There were a total of 88 oncology patients who underwent sperm banking at our institution during the study period. Types of cancer were various, with testicular cancer and hematological malignancies comprising the largest groups. Nearly 90% of the testicular cancer patients had their sperm preserved prior to the therapy, while only 53% of those with hematological disease did so. Evaluation of semen parameters for these groups revealed that oligozoospermia in testicular cancer patients, even prior to initiation of cancer therapy, was common. Five patients utilized their specimens for reproductive purposes. Of these, 3 patients successfully fathered a child. Our results suggest that sperm cryopreservation before initiation of cancer therapy in male oncology patients is under-utilized. Additionally, there is minimal use of cryopreserved specimens for reproductive purposes. This under-utilization is supposed to be due to physicians', especially hematologists', insufficient awareness toward chemotherapy-related infertility and the paucity of reports regarding reproductive outcome after freezing. More data should be compiled to help both physicians and patients who are considering sperm cryopreservation.

[A case report: recurrence of urothelial cancer in an ileal conduit].

A 48-year-old man presented complaining of lower abdominal pain, and was diagnosed with invasive bladder cancer. After neoadjuvant chemotherapy, cystoprostatourethrectomy and ileal conduit diversion were performed. At 53 years of age, bladder cancer recurred in the upper urinary tract and he underwent complete urinary tract extirpation. Histological examination revealed an urothelial carcinoma in an ileal conduit. Three years later, a local recurrence led to combined modality therapy including chemotherapy and radiotherapy. He is receiving maintenance chemotherapy for metastatic tumors. Urothelial carcinoma arising in an ileal conduit after radical cystectomy for bladder cancer is infrequently reported. To our knowledge, only 12 cases, including ours, have been reported.

[A case of elderly donor in living kidney transplant after radical radiotherapy for prostate cancer].

A 72-year-old man came to our clinic as a candidate of the donor of renal transplantation for his 44-year-old daughter. However, his serum PSA was found elevated, and he was diagnosed with stage C prostate cancer. He received neoadjuvant androgen deprivation therapy and subsequent IMRT as a definitive curative therapy. Since his PSA remained at a very low level after IMRT for three years, we performed systematic 16-site prostate biopsy, which revealed no viable prostate cancer cells. His renal function seemed to be normal and no functional difference was noted between the two kidneys. Then, his left kidney was harvested by hand-assisted retroperitoneal laparoscopic approach, and transplanted to his daughter successfully. The suitability of a donor with two potential problems-advanced age and a history of prostatic cancer-was discussed, together with a review of the literature.