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Three months after an initial 6-week course ofintravesical bacillus Calmette-Guerin (BCG) given between January 1990 and March 2005, 94 (90%) out of 104 patients with carcinoma in situ (CIS) of the bladder achieved a complete response (CR). The 5- and 10-year recurrence-free rates were 67 and 60%, respectively (median follow-up 42 months). Three months after a second course ofintravesical BCG given to 23 patients who failed the initial induction course for CIS was evaluated. Of these, 96% achieved a CR, and the 5- and 10-year recurrence-free rates were 56 and 28%,respectively (median follow-up 23 months). Only one patient who received a second course of BCG therapy showed disease progression. Two of the 4 patients with BCG-refractory CIS of the bladder achieved CR after intravesical gemcitabine therapy and maintained a tumor-free status beyond 6 months. Five of the 16 patients showing disease progression had upper urinary tract cancer, 4 had recurrent or muscle invasive bladder cancer, 6 had prostatic involvement of CIS, and one patient had urethral recurrence. Three of the 16 patients died. Bladder preservation was achieved in 97 of the 104 patients, although 7 patients ultimately underwent radical cystectomy and urinary diversion for aggressive disease. In conclusion, some patients may be managed safely by repeated endoscopic resection and intravesical therapy with cystectomy postponed until objective evidence of progression exists.

A 63-year-old man underwent transurethral resection of a bladder tumor to treat superficial bladder cancer in 1995. Histological examination showed urothelial carcinoma, G2>G3 with carcinoma in situ (CIS) at the bladder neck. He underwent postoperative intravesical bacillus Calmette-Guerin (BCG) therapy. In June, 2003, he complained of rubor of his external urethral meatus and visited our clinic. Biopsies at the external urethral meatus and the fossa navicularis of the urethra showed CIS. Radiological examinations, cystourethroscopy and multiple biopsies from other sites of urothelium, including bladder and urethral mucosa, did not reveal any other malignancies. Thereafter, partial penectomy and bilateral inguinal lymphadenectomy were performed. Histological examinations showed CIS at the urethral mucosa of the fossa navicularis and the skin of the glans penis. Postoperative urine cytologies were negative.

We report a rare case of inflammatory pseudotumor of the prostate. A 42-year-old man with a history of hematospermia and chronic prostatitis presented with difficulty in voiding. Cystoscopy demonstrated a large non-papillary tumor occupying the prostatic urethra along with two bladder stones. Magnetic resonance imaging (MRI) demonstrated a 7-cm prostatic mass protruding toward the bladder and the rectum. Transrectal biopsy of the prostate demonstrated a fibrous lesion containing inflammatory cells without evidence of malignancy. We performed transurethral resection of the prostatic lesion to release the bladder outlet obstruction, followed by cystolithotripsy. Histopathological examination of the surgical specimen demonstrated a benign fibromuscular lesion with spindle cell proliferation, leading to a diagnosis of inflammatory pseudotumor. Postoperatively, the patient voided normally without any signs of recurrence on follow-up at five months. Inflammatory pseudotumor is an unusual benign lesion of unknown etiology. Only 10 previous cases of the disease involving the prostate have been reported in English and Japanese literature. Prostatic involvement of inflammatory pseudotumor may show a presentation similar to malignant prostatic sarcoma. Thus, accurate identification of this benign process is important in order to avoid unnecessary radical surgery.

We report a case of carcinoma in situ (CIS) of the bladder involving the prostate with an unusual invasive pattern following Bacillus Calmette Guerin (BCG) therapy. A 41-year-old man achieved complete response after a course of intravesical instillation of BCG for diffuse CIS of the bladder. Two years later, urine cytology became positive. We performed random biopsy of the bladder and urethra three times and examined the bilateral upper urinary tract with retrograde pyelography and split urine cytology. However, none of these examinations revealed any malignant features, leading to a suspicion that the prostate was the recurrent site. Transrectal needle biopsy of the prostate revealed urothelial carcinoma (UC) at the transition between bladder and prostate. Transurethral biopsy of the prostatic urethra also detected UC in a core of the bladder neck only. Under a diagnosis of UC involving the prostate, we performed total cystectomy with ileal conduit diversion. Histopathological findings of the surgical specimen showed prostatic stromal invasion of the tumor. In this case, CIS at the bladder neck might directly and silently invade the prostatic stroma, thus transurethral biopsy contributed little to the diganosis. We recommend transrectal needle biopsy of the prostate as well as TUR biopsy in such rare cases.

We here report our clinical experience with salvage therapy for patients with bacillus Calmette-Guerin (BCG)-refractory superficial bladder cancer and discuss current approaches to the disease, especially focusing on bladder preservation. First, we evaluated the efficacy of an initial 6-week course of intravesical BCG in 93 patients with carcinoma in situ (CIS) of the bladder. Of these, 91% achieved a complete response (CR) at the evaluation at 3 months. The 2- and 5-year recurrence-free rates were 71 and 67%, respectively (mean follow-up 39 months). These results support the intravesical BCG as a first-line therapy for CIS. Next, we assessed the efficacy of a second course of intravesical BCG for 16 patients who failed the initial induction course for CIS. Of these, 94% achieved CR at the evaluation at 3-month, and the 2- and 5-year recurrence-free rates were 62 and 46%, respectively (mean follow-up 28 months). None of the patients who received a second course had disease progression. Thus, a second course of BCG therapy seems to be a reasonable option for CIS patients failing the initial course. We also report our initial experience with intravesical gemcitabine therapy for 3 patients with BCG-refractory CIS of the bladder and 1 patient with recurrent multiple tumors. Gemcitabine (1500 mg in 100 ml saline) was given in the bladder for 1 hour twice weekly for a total of 12 treatments. The treatment was associated with minimal bladder irritation and systemic absorption, and was well tolerated except in a 90-year-old man who discontinued therapy because of grade 2 toxicity. Two patients achieved CR and maintained a tumor-free status beyond 14 months, suggesting that the intravesical gemcitabine is a promising salvage therapy for BCG-refractory superficial bladder cancer.

Between 1995 and 2004, 43 patients underwent radical cystectomy and urinary diversion for the treatment of invasive bladder cancer at our institution. Of these patients, seven who were 75 years old or older, were considered elderly. Survival and treatment outcome of these patients were compared to younger counterparts stratified into three groups by age at diagnosis (12 patients younger than 64, 12 patients 65 to 69 years, and 12 patients 70 to 74 years). Preoperative morbidity was encountered in 57% of the elderly patients, and 42% of the elderly patients had two or more complications. There was one operative death (14%) among the elderly patients but no such deaths in the 3 younger groups. The postoperative complication rate for patients age 75 years or older was 86%, compared to 75% for patients younger than 64, 75% for those age 65 to 69 and 83% for those age 70-74. The prevalence did not differ significantly between the older and youger patients. There were no cancer deaths among the elderly patients, but 8 of the 36 younger patients died of cancer. The cancer-specific 5-year survival rate was 100% at 34 months in the elderly population. These findings suggest that radical cystectomy and urinary diversion is a relatively safe procedure and a curative operation is worth attempting in elderly patients with invasive bladder cancer, if they are in generally good health.

We report a case of pyoderma gangrenosum of the penis presenting as Fournier's gangrene. A 77-year-old man who had undergone radiotherapy for localized prostate cancer 16 month earlier, presented with penile pain and fever. Symptoms began with erythema and induration on the dorsal surface of the penile shaft followed by spontaneous purulent drainage with severe pain. Magnetic resonance imaging was unremarkable except for swelling of the penile skin. Biopsy of the ulcerative penile lesion demonstrated a nonspecific inflammation without vasculitis or malignancy. Despite broad-spectrum antibiotics and debridement, the penile lesion extended and new satellite lesions developed as pustules on the glans. Since cultures were negative for aerobic and anaerobic bacteria, a course of intravenous prednisolone was then initiated at 100 mg/day. Within 24 hours the temperature normalized, progression of the penile lesions stopped and became convalescent. The steroid was then tapered and discontinued. The penile lesions healed slowly during the subsequent 1-month period. Based on the clinical course and histopathological findings as well as exclusion of other ulcerative conditions, a diagnosis of pyoderma gangrenosum was made. Penile involvement of this non-infectious ulcerating skin disease has rarely been reported. Pyoderma gangrenosum affecting the penile skin, such as that in present case, may show a similar presentation as Fournier's gangrene. Prompt differential diagnosis is mandatory since effective management for each processes is markedly different.

Renal stone formation has been explained by the physicochemical theory; i.e., nucleation, growth and aggregation of crystals in the urine. Current medical prevention is based on this theory and seeks to modulate promoters and inhibitors of stone formation. Recent studies have identified increasing numbers of macromolecular inhibitors such as glycosaminoglycans, bikunin, osteopontin and urinary prothrombin F1. These appear to be more important than low-molecular inhibitors like citrate. On the other hand, many investigators have focused on the role of tubular epithelial cells in stone formation. While crystal retention in the nephron has been considered necessary for stone formation, we and others have found that calcium oxalate crystals can bind to renal epithelial cells. Moreover, available evidence suggests that oxalate and/or calcium oxalate crystals can damage renal epithelial cells and enhance crystal binding. Concurrently, oxalate exposure induces genes coding macromolecular inhibitors, which are supposed to be a protective mechanism against stone formation. Thus, understanding of the mechanisms involved in kidney stone formation could lead to new therapeutic approaches to preventing stone recurrence. However, clinical application of the prophylactic approaches proposed here awaits further progress in basic research using rapidly growing new technologies. Application of the DNA microarray technique to the rat stone model may provide a clue to understanding stone forming process at the genetic level. In addition, case-control association analysis using single nucleotide polymorphism as a marker may be useful for detecting susceptibility genes in patients with calcium stone disease.

We report a case of collecting duct carcinoma (Bellini duct carcinoma) producing carcinoembryonic antigen (CEA). A 61-year-old man visited our hospital because of a left renal mass detected by ultrasonography in an other hospital. Computed tomography showed a low density tumor measuring about 3 cm in the left kidney. Angiography demonstrated a hypovascular tumor. The serum level of CEA was increased to 20 ng/ml. (normal < 7 ng/ml). Left radical nephrectomy was performed. Histological examination revealed collecting duct carcinoma with papillary growth (T1aN1M0). Cancer cells showed a positive immunohistochemical staining for CEA. Under a diagnosis of CEA-producing collecting duct carcinoma of the left kidney, the patient underwent systemic chemotherapy (M-VAC). The serum level of CEA decreased to the normal level after the nephrectomy, but six months postoperatively, metastatic bone tumor at the left pelvic bone was revealed on the plain film and at the same time, the CEA level was increased again.

A tumor mass covered with scrotum-like skin on its tip was found on the perineal region of 3-year-old boy since his birth. The mass was diagnosed as congenital lipoma, which was resected, because of its gradual enlargement. Histopathological findings of the tumor indicated perineal lipoma, and the scrotum-like portion was diagnosed as an accessory scrotum. In the Japanese literature, 7 congenital perineal lipomas (6 males, 1 female) have been reported and all male cases except 1 case (no description about scrotum) were accompanied with an accessory scrotum. We conclude that there may be a close relationship between congenital perineal lipoma and accessory scrotum.

A technique of parathyroidectomy based on our experience of fifteen cases with primary hyperparathyroidism was described. The success of the surgery would require an ability of the surgeon to be delicate in technic, but recently this operation itself has become less invasive and complicated. It is emphasized that the urologists should chose parathyroidectomy with priority because treatment of primary hyperparathyroidism is quite important for some patients with urinary calculous diseases.

Five hundred and nineteen patients with primary bladder cancer were treated between January, 1969 and December, 1984, 12 of whom had developed upper urothelial tumors. These patients had received various transurethral treatment for the primary bladder lesions, except for one patient who had undergone total cystectomy and ileal conduit diversion. Overall incidence of patients with upper urinary tract tumors following bladder cancer was 2.3%. The incidence of patients with treated bladder tumors (13.2%) for dye workers was higher than that for the general population (1.1%). The interval between initial treatment of the bladder tumor and diagnosis of the upper tract tumor ranged from 7 to 170 months (mean 70 months). The incidence of upper tract tumors increased with the passage of time. We conclude that the occurrence of upper urinary tract tumors following primary bladder cancers is promoted by nonspecific chemical irritants against the urothelium already made unstable by certain urinary chemical carcinogens.

According to the records of Wakayama Labor Standard Office, at least 1,085 workers had been exposed to benzidine or beta-naphthylamine in the dyestuff factories in Wakayama City. By October 1988, 101 of them (9.3%) were confirmed to have urinary tract tumors. Including 2 other cases exposed in Osaka, a total of 103 cases of occupational uroepithelial cancer were studied here clinically. Site of tumors was bladder in 91 cases, renal pelvis in 2, ureter in 5 and papillomatosis type in 5. The age at the time of diagnosis ranged from 25 to 87 years with a mean of 53.8 years. The average latent period was 22.7 years, but the older the age of the worker at the start of exposure, the shorter was the latent period. In Wakayama, the proper system of healthy examination for chemical workers using urinary cytology was begun in 1970. Since then, more tumor cases have been discovered in comparison to the patients admitted with subjective symptoms of hematuria. The effectiveness of this group examination was significant in the incidence of total cystectomy in surgical treatment and in survival rate. In the comparative study between the groups of patients with occupational and spontaneous bladder cancer, the average age at diagnosis in the former was about ten years younger. Although the histological grade of tumor was not different between the two groups, the incidence of total cystectomy was lower and the survival rate was significantly higher in the occupational group.

Two cases of adenomatous polyps with prostatic type epithelium are reported. The first case was of a 62-year-old male suffering from asymptomatic hematuria. Cystoscopic findings showed an urethral tumor in the prostatic urethra. He was treated by transurethral resection of the prostate. The second case was of a 47-year-old male with complaints of hematuria and doubtful findings in urinary cytology. Cystoscopic findings showed that he had an urethral tumor in the prostatic urethra as well as bladder tumor. Both were resected transurethrally. Histological examination revealed that both urethral tumors were papillary adenoma of the prostatic urethra, corresponding to the adenomatous polyps with prostatic type epithelium in the classification of AFIP. The peroxidase-antiperoxidase complex method was performed using the anti-prostatic acid phosphatase antibody and anti-prostatic-specific antigen antibody, and positive reactions were obtained which confirmed that the tumors originated in the prostatic tissue. Benign urethral tumor in males is not common and description of adenomatous polyps with prostatic type epithelium is very rare. We could find only 11 cases in the Japanese literature.

A case of bilateral renal angiomyolipoma without tuberous sclerosis is reported. A 49-year-old woman was admitted to the general practitioner with a sudden onset of severe left flank pain. An excretory urogram and ultrasonogram revealed an enlargement of the left kidney. She was subsequently referred to our clinic for further investigation and treatment. Computed tomographic scan and magnetic resonance imaging using Tl-weighted image showed several tumors with a fatty, dense area in the bilateral kidney. An arteriogram demonstrated a hypervascular renal mass with aneurysms in her left kidney. Diagnosis of bilateral renal angiomyolipoma was confirmed by percutaneous needle biopsy. Superselective embolization of the tumor was successfully performed, preserving normal renal tissue. Gelatin sponges containing Carboquone (CQ sponge) were used as embolic material. Angiomyolipoma has become relatively easy to diagnose by CT, ultrasound, MRI and so on. However, there are some cases of angiomyolipoma which are indistinguishable from renal cell carcinoma using these modes of testing. Therefore, in selecting a conservative management, we indicated that percutaneous biopsy or open biopsy should be done to confirm the results of the above procedures. Moreover, therapeutic embolization for angiomyolipoma was concluded to be very useful.

Sixteen patients with locally advanced or metastatic bladder cancer were treated with cis-diamminedichloroplatinum (cis-DDP) alone or in combination with other drugs. Eight patients were given cis-DDP intravenously, 6 patients intraarterially and 2 by both methods. Seven patients (44%) showed a partial response, 2 showed a minor response and 4 remained unchanged. Of the 6 patients treated with arterial infusion, 3 achieved a partial response while only 2 of the 8 patients administered intravenously showed a partial response. Eight patients with deeply invasive bladder cancer were treated with cis-DDP alone or in combination with other drugs following radical cystectomy. Cis-DDP was administered every week for 3 courses and every month for 12 courses at a dose of 50 mg and cis-DDP, adriamycin and 5-FU (CAF) were administered at 3 weeks interval for 3 courses and every month for 12 courses. All patients in this group were alive with a median survival of 20 months. One patient had a recurrence 5 months postoperatively. Adjuvant chemotherapy with cis-DDP or their combination was effective. Toxicity was generally tolerable.