[A Case of Inflammatory Myofibroblastic Tumor of The Bladder Treated with Partial Cystectomy].

A 60-year-old woman with extensive hematuria visited our hospital. Cystoscopy revealed a tumor with an edematous surface on the left lateral wall of the urinary bladder. To diagnose the tumor, we performed a transurethral resection of the bladder tumor. Pathological examination suggested leiomyoma. Four weeks after the transurethral resection, magnetic resonance imaging revealed an increase in the bladder tumor. She received partial cystectomy. Pathological analysis revealed an inflammatory myofibroblastic tumor. No recurrence was observed 9 months after the initial operation.

Effect of Levofloxacin on the Efficacy and Adverse Events in Intravesical Bacillus Calmette-Guerin Treatment for Bladder Cancer: Results of a Randomized, Prospective, Multicenter Study.

BACKGROUND: Although bacillus Calmette-Guerin (BCG) is a standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), a high rate of adverse events with a variety of grades remains a difficulty. OBJECTIVE: In this randomized, prospective, multicenter study, we examined whether levofloxacin, given after each intravesical instillation of BCG, could improve its tolerance in patients with intermediate- to high-risk urothelial carcinoma of the bladder without compromising its efficacy. DESIGN, SETTING, AND PARTICIPANTS: Overall, 106 Japanese patients (85 men and 21 women; age: median, 69.5 yr) with primary or recurrent NMIBC were randomized after transurethral resection to induce treatment with intravesical BCG plus levofloxacin (group 1) or BCG alone (group 2). INTERVENTION: Patients who underwent intravesical instillation of BCG were randomized with or without levofloxacin administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events were assessed using the National Cancer Institute-Common Toxicity Criteria version 3.0. Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. RESULTS AND LIMITATIONS: There was no significant difference in baseline characteristics between the groups. The completion rate of group 1 (85.5%) was not significantly lower than that of group 2 (76.5%; p = 0.321). There was no significant difference in the completion rate of patients with pollakisuria, painful micturition, gross hematuria, fever elevation, and others between the groups. The incidence of adverse events in patients with high-grade pollakisuria (7.3% vs 25.4%, p = 0.041) and fever (0% vs 9.1%, p = 0.034) was significantly lower in group 1. The 5-yr progression-free and cancer-specific survival rates were significantly better in group 1. CONCLUSIONS: Prophylactic levofloxacin administration may reduce the severity of adverse events and contribute to better outcomes from BCG intravesical therapy in patients with NMIBC. PATIENT SUMMARY: Levofloxacin administration seems to be a safe and effective therapy for non-muscle-invasive bladder cancer patients treated with bacillus Calmette-Guerin intravesical therapy.

Efficacy and safety of nivolumab for renal cell carcinoma in patients over 75 years old from multiple Japanese institutes.

PURPOSE: Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab's efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years. METHODS: From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and < 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also compared between the two age-groups. RESULTS: The median follow-up duration after nivolumab initiation was 10 months. At the time of nivolumab initiation, 22 and 96 patients were aged ≥ 75 and < 75 years, respectively. Intergroup differences in patient characteristics except for age were not significant. Furthermore, intergroup differences in ORR (14 vs 23%; P = 0.367), PFS (HR 0.74, 95% CI 0.37-1.51; P = 0.414), and median OS (HR 1.29, 95% CI 0.68-2.46; P = 0.433) were not significant. The incidence of nivolumab discontinuation due to AEs was significantly higher in the ≥ 75 years group (27% vs 7%; P = 0.028), although the intergroup difference in the AE incidence rate was not significant (55% vs 43.8%; P = 0.535). CONCLUSIONS: Nivolumab's effectiveness was comparable between the two patient groups, except for early AE-related discontinuation in the ≥ 75 year group.

Efficacy of anti-PD-1 antibody nivolumab in Japanese patients with metastatic renal cell carcinoma: A retrospective multicenter analysis.

To evaluate the efficacy and safety of anti-PD1 therapy (nivolumab) in advanced renal cell carcinoma (RCC) in a clinical setting. Between March 2013 and January 2018, 33 patients with RCC (27 men and 6 women) were treated with nivolumab. Before anti-PD1 treatment, 12, 9 and 12 patients received one, two, and three or more therapies, respectively. Objective response, survival rate, and clinical adverse events were evaluated by the revised RECIST criteria (version 1.1). The median patient age was 68 years (range: 37-79). In total, 14 (42%) patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 while 17 (52%) and two (6%) had an ECOG PS of 1 and 2 or higher, respectively. One (3%), 24 (73%) and eight (24%) were classified as having favorable, intermediate, and poor risk, respectively. The median follow-up duration after nivolumab initiation was 26 months (range: 1-131). The median progression-free and overall survival were 10.3 months and 45.9 months, respectively. Nivolumab was associated with a disease control rate of 58%, with an objective response of 24% (complete response, 1; partial response, 7; stable disease, 11; progressive disease, 10; not assessed, 4). A total of 15 (46%) patients experienced adverse events, of which six were severe (grade 3 or more) and 10 were immunotherapy-related. This study examined the initial experience of nivolumab administration in Japanese patients with advanced RCC. Our results suggest that nivolumab can achieve acceptable outcomes in a real clinical setting, with outcomes that are comparable to those of clinical trials.

COMPARISON BETWEEN EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY AT 120 AND 60 SHOCKWAVES PER MINUTE FOR TREATMENT OF URINARY STONES.

(Purpose) It has recently been suggested that a slow delivery rate of shockwaves by extracorporeal shock wave lithotripsy (SWL) improved treatment outcomes for urinary stones. We retrospectively analyzed the treatment outcomes of different shockwave delivery rates at 120 and 60 shockwaves per minute. (Patients and method) A total of 88 patients were treated at a fast delivery rate of 120 shockwaves per minute between July 2010 and April 2012, and 139 patients were treated at a slow delivery rate of 60 shockwaves per minute between May 2012 and May 2014 (n=227) using a Sonolith® Praktis lithotripter. The treatment outcome of stone-free rate (SFR) after one SWL session was assessed at four weeks. (Result) SWL at 60 shockwaves per minute resulted in a significantly higher SFR compared with SWL at 120 shockwaves per minute (39.8% and 59.0%, respectively, p=0.0047), particularly for upper ureter (U1) stones (53.1% and 72.0%, respectively, p=0.028). Multivariate analysis showed that younger age, stone sizes of 10 mm or less, U1 stones, and slow delivery rate were significant predictors of a stone-free outcome. There were fewer adverse events after the delivery rate of 60 shockwaves per minute (p=0.058). (Conclusion) Our study suggests that SWL at 60 shockwaves per minute should be recommended to successfully treat urinary stones using the Sonolith® Praktis lithotripter.

Successful renal transplantation in the right iliac fossa 2 years after serious deep venous thrombosis in a patient with systemic lupus erythematosus.

Deep venous thrombosis (DVT) possibly occurs in the perioperative period, and induces serious complications such as a pulmonary embolism. On the other hand, allograft renal vein thrombosis leads to a high incidence of graft loss. We experienced a case in which a serious DVT occurred prior to renal transplantation; however, a successful renal transplantation in the right iliac fossa was performed after 2 years of anticoagulant therapy. It is suggested that the external iliac vein even after suffering from DVT can be anastomosed to an allograft vein successfully, when enough blood fl ow or a lower venous pressure is confirmed. However, one should be aware of the risk factors and the adequate management of thrombosis in renal transplantation because of the serious complications of DVT and the poor prognosis of allograft vein thrombosis.

A novel antireflux technique using an intussuscepted ileal segment.

A novel surgical technique of antireflux with an ileal conduit for urinary diversion is presented with our early results. The mid 8-cm portion of an isolated terminal ileum is intussuscepted. After skeletonization of the mesenterial vasculature, 3 rows of 4 mattress seromuscular silk sutures are placed on the ileum. By tying the sutures successively, the ileum is intussuscepted and the resultant nipple is secured simultaneously between its outer and inner layers. The outer nipple layer and the recipient ileal layer are further fixed as a whole by placing 3 rows of metal staples. The nipple base is secured by interrupted silk sutures and the mesenterial defect is closed. This technique was applied to 30 patients undergoing rectosigmoidal bladder procedure, a modified ileocecal rectal bladder, in which the antireflux conduit was interposed between the ureters and the rectosigmoidal pouch. Ureteral reflux was observed in none of the patients during a mean follow-up period of 29.9 months. Of the 60 renal units, 53 (88.3%) had normal pyelography and 7 (12.7%) showed mild hydronephrosis at 3-6 months postoperatively. This antireflux technique is simple and reliable, and can be applied to other urinary diversion/reconstruction surgeries, such as the continent reservoir, orthotopic neobladder, and/or bladder augmentation.

Rectosigmoidal bladder utilizing intussuscepted ileal segment: a surgical technique for urinary diversion and experiences in 30 patients.

BACKGROUND: We previously reported that the ileocecal rectal bladder consists of interposition of an intussuscepted ileocecal segment between the ureters and the rectum for those in whom the urethra is not available. Although the ileocecal rectal bladder has been well accepted by most patients, it requires an extensive preparation along the ascending colon. We present a modified operation technique (rectosigmoidal bladder) by using the ileal segment alone as an interposing antireflux component and by using the sigmoidal segment to augment the rectal capacity. METHODS: From February 1993 to July 2002, 30 patients with a median age of 64 years underwent construction of a rectosigmoidal bladder. Median follow-up period was 26 months (range, 13-125). The follow up was carried out using clinical and functional assessments such as evacuation status, serum chemistry and radiographic evaluation of the upper urinary tracts and rectosigmoidal pouch. To assess the postoperative health-related quality of life, we carried out a survey comparison of the ileocecal rectal bladder patients and the rectosigmoidal bladder patients. RESULTS: No operative or urinary diversion-related postoperative mortality was encountered. All rectosigmoidal bladders had sufficient capacity, with no evidence of urinary reflux or daytime incontinence. When compared with our previous procedure, the ileocecal rectal bladder, the present procedure had advantages with respect to complications with urine-fecal leak and acidosis. There were no differences in mean operation time, or in the health-related quality of life survey, between the two procedures. CONCLUSIONS: Our experience showed that this technique should be considered for those in whom the urethra is not available.

[Angioplasty for the intimal dissection of graft artery immediately after blood reflow: a successful case of renal transplantation].

A 58-year-old woman, who had been suffering from chronic renal failure on hemodialysis since 1999, underwent living renal transplantation on January 14, 2003. The donor was her husband, and his left kidney was resected by a hand-assisted retroperitoneoscopic technique. Vascular clamps were removed after vascular anastomoses, but the color of two-thirds of the graft back side was dark, and urine excretion was not observed for 1 hour. The intimal dissection of the graft artery developed false lumen that occluded the blood flow to the transplanted kidney. The graft was resected from the recipient, and an angioplasty was performed for the false lumen of the graft artery after the second cold preservation. The graft with repaired artery was re-transplanted, and urine excretion was observed immediately after operation. Total ischemia time was 5 hours. Clinicopathological acute rejection episode and stenosis of graft artery did not occur for 6 months after operation. The intimal dissection of graft artery might occur at the time of catheterization on the perfusion for cold preservation and/or vascular anastomosis.

[A case of organ sparing surgery for metachronous bilateral testicular tumor with maintaining testicular function].

A 28-year-old man, who had undergone right orchiectomy and prophylactic irradiation for stage I seminoma 6 years ago, developed left testicular tumor. Since the secondary tumor was localized in the lower pole of the testis, partial orchiectomy was performed with an attempt to preserve the testicular function. The pathological finding of the surgical specimen was a mixed type testicular tumor consisting of seminoma, embryonal carcinoma and teratoma elements. Postoperative chemotherapy with 3 courses of BEP regimen resulted in azoospermia, but the impaired spermatogenesis recovered to a normal range within 18 months with no evidence of tumor recurrence and his wife delivered a healthy baby 2 years later. For the synchronous or metachronous bilateral testicular tumors, the combination of organ sparing surgery and chemotherapy could be a treatment of choice.

[A case of renal cell carcinoma in tuberous sclerosis].

A 43-year-old woman with mental retardation, epilepsy, and urinary stone disease had a right renal tumor. Acne-like anthema around the nose and dental pits of the nine teeth were typical signs of tuberous sclerosis (TSC), and the biopsy finding of the facial anthema was consistant with TSC. The pathological diagnosis of laparoscopic nephrectomy was renal cell carcinoma in the hemorrhagic cyst. The TSC-related renal cell carcinoma tends to develop bilaterally in younger individuals compared with the sporadic RCC. This case is the 27th case of TSC-related RCC in Japan.

Chronopharmacokinetics of tacrolimus in kidney transplant recipients: occurrence of acute rejection.

The circadian variation of clinical pharmacokinetics of tacrolimus was studied using 16 adult renal transplant recipients 1 month after the operation. The recipients were administered tacrolimus twice a day (9 a.m. and 9 p.m.), and whole-blood samples were obtained just prior to and 1, 2, 3, 6, 9, and 12 hours after oral administration. Histological specimens of transplant kidney were collected by an allograft core biopsy on day 28 after the transplantation. There were no circadian changes in the area under the concentration-time curve (AUC0-12) (214 ng.h/mL during daytime vs. 223 ng.h/mL during nighttime) resulting from morning and night doses. A slight delay in mean residence time (MRT0-12) and time to the peak concentration (tmax) was found after night doses, but there was no statistical significance. Three patients (18.8%) had a clinical acute rejection (AR) episode 4 to 6 weeks after transplantation, and AUC0-12 at nighttime was significantly lower (18.4% on average) in patients with AR in comparison to those without AR. There was no statistical significance in maximum concentration (Cmax) or morning/night trough levels between patients with and without AR. In regard to the correlation between tacrolimus concentrations in each sampling time and AUC0-12, the morning trough concentrations were less predictable for daytime AUC0-12 (r2 = 0.125), but there was a weak correlation to nighttime AUC0-12 (r2 = 0.424). Tacrolimus concentrations at 2, 3, and 6 hours after the morning dose (C2, C3, and C6) had a good correlation against daytime AUC. The results of this study indicate that the variance on the clinical pharmacokinetics of tacrolimus between daytime and nighttime in renal transplant patients is not significant, while the lower nighttime AUC corresponded to the occurrence of AR.

[Acceleration of ATP-induced contraction in the obstructed bladder of the rat].

BACKGROUND: Detrusor instability is one of the most common problems in patients with lower urinary tract obstructive diseases, such as benign prostatic hyperplasia. Adenosine triphosphate (ATP) has been associated as a neuronal component in the detrusor instability. MATERIALS AND METHODS: Ninety-six female Splague-Dawley rats were studied. Outflow obstructions were created by ligature of the urethra over which a catheter was placed. Changes in the bladder capacity, and an isovolumetric contractile response to pharmacologic antagonists were studied in the obstructed rats for a period of from one day to four weeks. RESULTS: The bladder capacity of rats obstructed for four weeks increased significantly. Maximum bladder contraction pressure with the use of atropine medication was inhibited in 60 percent and, 30 percent of in the control group, respectively. The inhibitory effect of the maximum bladder contraction pressure by the pyridoxalphosphate-6-azophenyl-2', 4'-disulphonate (PPADS) dosage after the atropine dosage was not recognized it in the control group, but the effect was recognized powerfully in the obstructed group. CONCLUSION: In the obstructed bladder rat, strong rise of the bladder contraction by P2X receptor with a lower urinary obstruction was accepted, and that result reflects positively. Therefore, it was guessed that the result was an end of the compensatory mechanism of unstable bladder.

[A case of retroperitoneal extramedullary plasmacytoma].

A 69-year-old woman visited a hospital with a complaint of left abdominal dull pain. A computed tomographic scan demonstrated a large tumor with central necrosis in the left retroperitoneum, and an angiography revealed hypervascular tumor which was fed from splenic, left renal, left gastric and left colic arteries. Renal cell carcinoma with extrarenal progression was pre-operatively suspected, and a resection was attempted. However, since the celiac artery was involved in the tumor, only a biopsy was performed. The histopathological finding of the biopsy specimen was a plasmacytoma. A combination of chemotherapy and radiation therapy resulted in a marked reduction of the tumor. There was no evidence of tumor progression one year after the chemotherapy.

[Retroperitoneoscopic hand-assisted nephrectomy for live donor: Akita University experience].

PURPOSE: Laparoscopic nephrectomy is being employed in renal transplantation because of its minimal invasiveness, and several modifications in surgical procedures have been proposed. We devised a new technique of retroperitoneoscopic hand-assisted nephrectomy (RHAN) for live donor. We report the early experiences with this technique in 5 cases of live renal graft donor. TECHNIQUES AND SUBJECTS: The donors are placed in a modified decubitus position under general anesthesia, and all the laparoscopic surgical procedures were performed retroperitoneally using 3 port sites and a sealing device (LAP DISC) under a pressure of 10 mmHg. The LAP DISC is placed through a para-rectus abdominal skin incision of approximately 8 cm in length into the retroperitoneal cavity and used as a rout for instrumental as well as hand-assisted manipulations during the surgery. The hand-assistance through the LAP DISC made the surgical manipulation considerably easier and allowed the immediate removal of the graft after the interruption of the renal blood flow. This procedure was applied to 5 subjects, 4 in the left and one in the right kidney. RESULTS: The operating data were 264-359 min for operating time, 0.9-3.9 min for warm ischemic time and 40-755 ml for intra-operative blood loss, respectively. The serum creatinine level of the recipients at day 7 was 0.9-2.7 mg/dl. These values, except for operating time, were at the same range as those of the open live donor nephrectomy in our clinic. The 5 donors discharged 7-9 days after RHAN without any surgical complications. CONCLUSION: Our technique of RHAN will be a minimal invasive one in terms of both for the donors and the grafts, and be widely acceptable for donor nephrectomy on either side.

[A case of long-term remission with salvage surgeries for chemotherapy-resistant germ cell tumor of testis].

A patient with non-seminomatous germ cell tumor of testis underwent operations for metastases in the lung and mediastinum three times, when the serum AFP level remained remarkably high despite of intensive chemotherapy, and has been disease-free for three years after the last treatment. Our experience illustrates that the salvage surgery even under high serum marker levels may provide a beneficial outcome for selected cases of chemotherapy-resistant germ cell tumors.

[Early results in the initial 15 cases of laparoscopic radical prostatectomy in Akita University Medical Center].

We herein report our experience and early results of laparoscopic radical prostatectomy in 15 cases of localized prostate cancer (11 T1c and 4 T2a tumors) performed between March 2000 and October 2001. The operative procedure was almost identical to the Montsouris technique. Conversion to the open procedure was required only in the first case because of a widely opened bladder neck that involved the ureteral orifice. No severe intraoperative or postoperative complications were observed. The mean operating time and blood loss was 383 minutes and 640 ml including intraoperative urine, respectively. Only one patient required blood transfusion. All 14 patients with a successful procedure could take fluid and walk freely on postoperative day 1. Twelve (86%) of the 14 patients could take food on postoperative day 1 and a Foley catheter was successfully removed on day 6 to 8 in 12 (86%) cases. Histologically, positive surgical margin was observed in 5 (33%) cases and all of them were considered non-organ confined (pT3 or more). Without adjuvant hormonal therapy, biochemical (PSA) failure was observed in 5 (36%) cases (median follow-up period: 11 months). Continence has been well maintained in 12 patients with no need for a pad by 3 months postoperatively and 2 patients are using only 1 pad/day for caution's sake. In terms of early postoperative recovery, intraoperative blood loss and maintenance of continence, laparoscopic radical prostatectomy may give a satisfactory result. Although long-term follow-up is required to assess disease control and maintenance of sexual function, laparoscopic radical prostatectomy may become an alternative for the treatment of organ-confined prostate cancer.

[The effects of the antagonists of muscarinic acetylcholine receptor subtypes in rat brain on urinary bladder contraction].

BACKGROUND: Pontine micuturition center and storage center are controlled by upper brain. Pharmacological and molecular biological data indicate the distribution of muscarinic receptor subtypes in rat brain, however, the effect of central muscarinic cholinergic mechanisms on the bladder activity has not been evaluated. We investigated the diversity of effect of each subtype in rat brain. METHODS: The muscarinic agents such as muscarine (non-specific agonist), atropine (non-specific antagonist), pirenzepine (M1 receptor antagonist), AF-DX116 (M2 receptor antagonist) and 4-DAMP (M3 receptor antagonist) were administrated with intracerebroventricular injection (I.C.V. group) or intravenous injection (i.v. group). The drug effects on rhythmic bladder contraction were investigated. RESULTS: In I.C.V. group, the bladder contraction pressure were reduced by atropine, pirenzepine and 4-DAMP. The contraction time were shortened by pirenzepine and 4-DAMP but extended by AF-DX116. The contraction frequency was decreased by AF-DX116. Whereas AF-DX116 in i.v. group reduced the contraction pressure but did not cause any changes of the contraction time and the frequency. Other agents in i.v. group had same tendency with those of I.C.V. group except for intensity. CONCLUSION: That is to say AF-DX116 in I.C.V. group facilitate both micuturition center and storage center. In other words, these data indicate M2 receptor in rat brain inhibits both micurition and storage center. In addition, the effect of AF-DX116 in brain suggests that the development of new drug which proceed to central neuron system might provide a new treatment of neurogenic bladder.