[Three Cases of Bilateral Metachronous Testicular Tumors].

We present three cases of bilateral metachronous testicular tumors. The patient in case 1 had a history of left orchiectomy for undescended testis at the age of 19. The pathological findings revealed germ cell neoplasia in situ. Twenty-four years later (age＝43), he was diagnosed with right testicular tumor with lymph node and lung metastasis (stage IIIc). Right orchiectomy was performed, and the pathological finding showed nonseminomatous germ cell tumor. He underwent chemotherapy, followed by lymph node dissection and lung metastasectomy. The patient in case 2 had a history of left orchiectomy for testicular tumor at the age of 41. The pathological finding of the left testis revealed seminoma (stage IA). Nineteen years later (age＝60), he was diagnosed with right testicular tumor and underwent right orchiectomy. Herein, the pathological finding showed seminoma (stage IA). The patient in case 3 had a history of right orchiectomy for testicular tumor at the age of 25. The pathological findings revealed seminoma (stage IS), and he underwent adjuvant radiation of the para-aortic field without subsequent recurrence. Fourteen years later (age＝39), he was diagnosed with left testicular tumor and underwent left orchiectomy. The pathological finding revealed seminoma (stage IB). The patient underwent adjuvant carboplatin monotherapy to prevent recurrence. Due to the long interval between the occurrence of bilateral metachronous testicular tumors (mean＝19 years ; three cases), long-term observation is necessary to detect the possible occurrence of contralateral testicular tumors. Contralateral testicular biopsy might be considered at the time of orchiectomy for unilateral testicular tumor if associated with testicular atrophy and/or a history of undescended testis.

[Comparison of Perioperative Outcomes between Open and Robot-Assisted Laparoscopic Radical Cystectomy].

We compared the perioperative outcomes of open (ORC) and robot-assisted laparoscopic radical cystectomy (RARC) for patients with bladder cancer. We retrospectively investigated the intraoperative and 90-day postoperative complications of ORC and RARC performed from March 2014 to September 2021 based on the medical records. Perioperative complications were categorized according to the Clavien- Dindo classification. We used the propensity score matching to adjust for the inherent bias of the different patient characteristics at baseline including gender, age, preoperative chemotherapy, and pathological T classification. Surgery time of RARC was significantly shorter than that of ORC, and blood transfusion was significantly less frequent in RARC than in ORC (3% vs 81%, p＜0.01). The rate of overall complications of Grade III/IV was lower in RARC (8%) than in ORC (25%) (P＝0.09). The prevalence of perioperative urinary tract infection, ileus, and abscess/infectious cyst was similar in ORC and RARC. In patients who underwent RARC, the complication rate was similar in extracorporeal and intracorporeal urinary diversion. Compared to ORC, RARC is more beneficial to reduce blood loss and severe complications.

[Treatment Outcome of Ureteral Reconstruction Surgery].

We retrospectively reviewed the surgical outcome of ureteral reconstruction that was performed in Asahikawa Medical University Hospital between 2005 and 2021. A total of 14 patients (3 males, 11 females; 15 ureters) were included in this analysis. The median age was 57 years old. The reason for ureteral reconstruction was ureteral injury or stenosis due to pelvic surgery in 9 patients, transurethral lithotripsy for ureteral stone in 3, ureteral invasion of sigmoid colon cancer in one and ovarian cancer in one. The site of ureteral reconstruction was proximal ureter in 2, middle in 3 and distal in 10. The surgical procedure was ureteroneocystostomy with Boari flap in 8 patients (57%), ureteroureterostomy in 4 (21%), transureteroureterostomy in one (7%), and transureteroureterostomy combined with Boari flap for bilateral ureteral stenosis in the remaining patient (7%). Postoperatively, vesicoureteral reflux, ileus and surgical site infection were observed in 3, 2 and 1 patient, respectively. No patient required nephrostomy or ureteral catheter, or any additional procedure after the surgery. There was no episode of febrile urinary tract infection after the surgery. The mean estimated glomerular filtration rate was, respectivery 75.8 and 78.5 ml/min/1.73 m2 before surgery and at 1-101 months (median of 18) after the surgery. In conclusion, satisfactory outcome was achieved after ureteral reconstruction surgery. We emphasize the importance of selecting the most appropriate procedure for ureteral reconstruction in each patient to prevent renal function deterioration and urinary tract infection.

[Initial Experiences of Dynamic Sentinel Lymph Node Biopsy (DSNB) in Patients with Penile Cancer].

We present 2 cases of penile cancer in which the inguinal lymph node was not palpable and inguinal lymph node dissection (ILND) could be safely avoided by conducting dynamic sentinel lymph node biopsy (DSNB). The first case was in a 54-year-old man complaining of penile tumor for at least 3 months. We performed partial penectomy and DSNB. The pathological diagnosis was squamous cell carcinoma (SCC), pT2-3. There was no cancer metastasis in sentinel nodes (0/2). There has been no recurrence for 6 years after operation. The second case was 65-year-old man suffering from penile tumor for at least 6 months. We performed partial penectomy and DSNB. The pathological diagnosis was SCC,pT2. There was no cancer metastasis in sentinel nodes (0/3). There has been no recurrence for 1 year after operation. ILND has been recommended for intermediate and high-risk penile cancer even in patients with non-palpable inguinal lymph nodes. However,the complication of ILND is very high. DSNB has the potential to avoid ILND if there is no cancer metastasis in sentinel nodes.

IMPROVEMENT OF GAMMA-RAY SUBTRACTION PROCEDURE FOR A CURRENT-MODE NEUTRON DETECTOR WITH A PAIR OF 6Li- AND 7Li-GLASS SCINTILLATORS.

A current-mode neutron detector with a pair of 6Li- and 7Li-glass scintillators has been developed to measure high-flux neutrons in a boron neutron capture therapy field. Neutrons are basically measured by subtracting gamma-ray component using current outputs from the 7Li-glass scintillator. In the present study, the difference in the gamma-ray sensitivity between the 6Li- and 7Li-glass scintillators and the neutron sensitivity for the 7Li-glass scintillator due to the 6Li contamination were also considered to improve the gamma-ray subtraction precision. The gamma-ray subtraction procedure was experimentally investigated in thermal neutron fields with 252Cf and 241Am-Be neutron sources, which have different gamma-ray intensities per unit neutron fluence. A linear relation between neutron fluence and current output was obtained for the neutron detector in the two types of thermal neutron fields with different gamma-ray intensities. It was found that the gamma-ray subtraction procedure is useful for current-mode neutron detectors.

Differential effects of depot formulations of GnRH agonist leuprorelin and antagonist degarelix on the seminiferous epithelium of the rat testis.

Despite their pharmacologically opposite actions, long-acting depot formulations of both GnRH agonists and antagonists have been clinically applied for treatment of androgen-sensitive prostate cancer. Sustained treatment with GnRH analogues commonly suppresses both the synthesis and release of gonadotropins, leading to depletion of testicular testosterone. To clarify the underlying differences in the effects of GnRH agonists and antagonists on spermatogenesis, we compared histological changes in the seminiferous epithelium after administration of depot formulations of GnRH agonist leuprorelin and antagonist degarelix to male rats. Testicular weight had markedly declined by 28 days after administration of both GnRH analogues, although the testicular weight was decreased more promptly by leuprorelin compared with degarelix. Shortly after administration, massive exfoliation of premature spermatids and anomalous multinucleated giant cells was observed in seminiferous tubules of leuprorelin-treated rats, probably via the initial hyperstimulatory effects on the hypothalamic-pituitary-testicular axis, whereas no discernible changes were found in those of degarelix-treated rats. Long term treatment with both types of GnRH analogues similarly induced a marked reduction in the height of the epithelium and deformation of apical cytoplasm in Sertoli cells, resulting in premature detachment of spermatids from the epithelium. Lipid droplets had accumulated progressively in Sertoli cells, especially in those of degarelix-treated rats. These findings clearly demonstrate the differences in the effects of GnRH agonists and antagonists on the spermatogenic process. This study suggests that an appropriate choice of GnRH analogues is necessary to minimize their adverse effects on spermatogenesis when reproductive functions should be preserved in patients.

[Successful Management by Immunoglobulin for Sunitinib-Induced Thrombocytopenia in a Patient with Advanced Metastatic Renal Cell Carcinoma].

An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-week-on, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×10(9)/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.

[Clinical Significance of Primary Tumor Resection in Patients with Metastatic Urothelial Carcinoma at Initial Presentation].

We retrospectively reviewed 67 patients who presented with metastatic urothelial carcinoma to the Department of Urology, Asahikawa Medical University Hospital between 2000 and 2013. Furthermore, 13 patients with comparatively longer survival (2 years or longer after diagnosis) were analyzed to find any clinical characteristics among these patients. The primary site was the upper tract in 41 patients and bladder in 26. The most frequent metastatic site was regional lymph nodes (49 patients), followed by viscera (36 patients) and distant lymph nodes (17 patients). Primary tumor resections were performed on 83% of the patients with only regional lymph node metastasis, but on only 35% of the patients with distant metastasis. Median overall survival (OS) of patients was 8.5 months in this series. Median OS of patients with only regional lymph node metastasis was 15 months, which was significantly longer than that (8 months) of patients with distant metastasis. Multivariate analysis revealed only regional lymph node metastasis and the number of metastatic sites were significant prognostic factors for OS. We further investigated the clinical characteristics of 13 patients with comparatively longer survival. Other than a small number of metastatic sites (1 or 2) and no distant lymph node metastasis, we could not find any significant characteristics to predict longer prognosis. The present study showed that primary tumor resection did not have a significant benefit on survival in patients with metastatic urothelial carcinoma at initial presentation. However, primary tumor resection should be considered when there is only regional lymph node metastasis and few metastatic sites.

Effects of chronic treatment with cilostazol, a phosphodiesterase 3 inhibitor, on female rat bladder in a partial bladder outlet obstruction model.

OBJECTIVE: To investigate whether bladder dysfunction after bladder outlet obstruction (BOO) could be altered by treatment with cilostazol, a phosphodiesterase 3 inhibitor (PDE3i). METHODS: Twelve-week-old female Sprague-Dawley rats were divided into 5 groups: groups 1 and 2, sham-operated rats and groups 3-5, BOO rats. Group 1 and 3 rats were given normal diet, group 2 and 5 rats were given high-dose PDE3i diet, and group 4 rats were given low-dose PDE3i diet. PDE3i was given within diet from the day of surgery. Four weeks after BOO, the bladder was excised and dissected into 4 longitudinal strips for isometric organ-bath assay. Contractile responses of bladder strips to electrical field stimulation (EFS), carbachol, and potassium chloride (KCl) were determined for each group. RESULTS: BOO induced a significant increase in bladder weight in groups 3-5 compared with groups 1 and 2. PDE3i treatment did not affect bladder weight in sham or BOO rats. Contractile forces in response to EFS, carbachol, and KCl in group 3 were about 20%-40% of those in group 1. Contractile responses to EFS or KCl in PDE3i-treated BOO rats were not significantly different from those in group 3. Only high dose of PDE3i treatment in BOO rats caused a statistically significant increase in the response to carbachol compared with group 3. CONCLUSION: PDE3i has a small but significant protective effect on the contractile dysfunction induced by a 4-week BOO in rats, although the increase in bladder mass was not altered. PDE3i could be a useful protection against contractile dysfunction of the obstructed bladder.

[A case of eosinophilic cystitis mimicking an invasive bladder cancer].

A 60-year-old woman was referred to our hospital because of gross hematuria, right lumbar pain and lower abdominal pain. Computed tomography (CT) scan revealed hydronephrosis of the right kidney, irregular bladder wall thickening at the right lateral and posterior portion and external iliac lymph node swelling of the right side. Laboratory data revealed disseminated intravascular coagulation syndrome (DIC) and eosinophilia. Because she developed a high fever that was caused by acute obstructive pyelonephritis of the right kidney, percutaneous nephrostomy was placed and the therapy for DIC was initiated. Pathological examination of transurethral resection of bladder tumor performed twice showed no malignancy but inflammatory infiltration of many eosinocytes, leading to the diagnosis of eosinophilic cystitis (EC). We considered the possibility of allergic reaction to the drugs she was taking as the etiology of EC and discontinued all drugs. Although eosinophilia was resolved afterward, she then developed brain infarction, followed by cerebral hemorrhage. She was transferred to a rehabilitation hospital for long-term care. CT scan that was performed 4 months after the initial presentation showed the resolution of hydronephrosis of the right kidney and external iliac lymph node swelling and the improvement of bladder wall thickness. Hydronephrosis of the right kidney has not recurred after removing the nephrostomy catheter. EC is a rare condition that could mimic an invasive bladder cancer. EC should be considered if bladder tumor is associated with eosinophilia. Therapeutic consideration for thromboembolic events should be made in patients with EC.

Bladder function in 17ß-estradiol-induced nonbacterial prostatitis model in Wistar rat.

OBJECTIVES: To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17ß-estradiol injection. METHODS: Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl. RESULTS: (1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP. CONCLUSIONS: In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

[Clinical investigation of extracorporeal endotoxin adsorption therapy in septic urinary tract infections].

OBJECTIVE: Severe urinary tract infection may lead to sepsis in some cases. In these cases, treatment must not only include drainage of the source of infection, but also management of systemic inflammatory response syndrome (SIRS). Blood purification therapy focused on endotoxin adsorption is thought to be a useful treatment method for this purpose. Herein, we clinically investigated the cases in which this treatment method was applied. SUBJECTS AND METHODS: A total of 22 patients underwent endotoxin adsorption therapy following diagnosis of sepsis at the department of urology, Hokkaido Social Welfare Association Furano Hospital during the last six years. Of these patients, six patients whose primary disease was urinary tract infection were included in the study. RESULTS: Patients comprised four men and two women with either pyelonephritis (n = 5; complicated by prostatitis in one patient) or pyonephrosis (n = 1). Primary diseases included urolithiasis (n = 4), vesicoureteral reflux (n = 1), and ureteric stenosis (n = 1). Urinary tract drainage included ureteral stent (n = 4), nephrostomy (n = 1), and cystostomy (n = 1), with concomitant use of continuous hemodiafiltration in one patient. Serum endotoxin levels were 3.2 pg/ml on average, and returned to normal following endotoxin adsorption therapy in all patients. A total of four strains of Escherichia coli and one strain of Klebsiella pneumoniae were identified as pathogenic bacteria. CONCLUSION: Hemodynamics was markedly stabilized following endotoxin adsorption therapy, and all patients survived. These findings indicate that endotoxin adsorption therapy should be actively considered as a treatment method for patients with sepsis secondary to urinary tract infection.

[Case report of advanced renal cancer that showed different responses to the alteration of therapeutic cytokines].

We report a case of advanced renal cancer that showed different responses to the alteration of therapeutic cytokines. A 73-year-old man presented with asymptomatic macrohematuria, and was diagnosed as right renal cancer (11 x 9 x 9 cm in diameter) with metastases to abdominal and mediastinal lymph nodes (cT3bN2M1, stage IV). Transluminal embolization of the right renal artery was performed, and then he was treated by intramuscular administration of natural human interferon (IFN)-alpha (Sumiferon; 6 x 10(6) units) three times a week. Four months later, lymph node metastases enlarged, and human interleukin-2 therapy (intravenous administration; 1.4 x 10(6) units) was initiated instead of IFN-alpha. However, lymph node metastases further enlarged and multiple lung metastases newly appeared in 5 weeks after the alteration of the therapy. Then, the treatment was switched to intramuscular administration of another natural human IFN-alpha (OIF; 5 x 10(6) units) three times a week. In 3 months after OIF administration, all lung metastases disappeared. Lymph node metastases have shown no progression for 9 months after the switch to OIF. Different responses to the two types of IFN-alpha in this case may be caused by the difference in the composition of IFN-alpha subtypes. Alteration of therapeutic cytokines, especially a switch from one type to another IFN-alpha may be one of worth attempts even if other cytokines are not effective.

[Solitary genital leiomyoma of the tunica dartos: a case report and review of the literature in Japan].

We report a case of solitary genital leiomyoma arising from the tunica dartos of the scrotum. A 43-year-old man complained of a slightly tender left scrotal mass that had enlarged over approximately 17 years. On physical examination, the tumor was pedunculate and attached to the lower pole of the left scrotum. The tumor was clearly separate from scrotal contents such as the testis, epididymis, and spermatic cord. Ultrasonography showed the tumor to be 20.0 X 23.5 mm in diameter. Other laboratory examination findings were normal. Under local anesthesia, the tumor was resected at its base with overlying skin. On histopathological examination, the tumor consisted of interlacing bundles of smooth muscle cells, which were positive for vimentin, desmin, and a-actin. The tumor was diagnosed as leiomyoma arising from the scrotal tunica dartos. As solitary genital leiomyoma of the tunica dartos is rare, we have presented this case history and reviewed 23 cases that occurred in Japan.