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Intravesical chemotherapy is performed after transurethral resection of bladder tumor (TURBT) for superficial bladder cancer. We conducted a prospective randomized controlled study on the prophylactic effects of intravesical instillation of epirubicin (EPI) against recurrence to determine the effective administration schedule. Between April 1999 and March 2003, 54 patients with superficial bladder tumor (pTa or pT1, and G1 or G2 cancer) were assigned to two groups (25 in Group A, 29 in Group B) after TURBT. The schedule of instillation (intravesically 40 mg of EPI dissolved in 40 ml saline) was subsequently once every two weeks for 3 months (7 times) starting one week after TURBT (Group A, short period), and subsequently added every two weeks for 3 months starting 6 months after TURBT (Group B, long period). The patients were followed up by cystoscopy and urinary cytology. There was no significant difference in non-recurrence rates after either one year (A; 62.5%, B; 82.8%) or three years (A; 53.6%, B; 67.3%). A univariate analysis demonstrated that tumor grade and staging were significant predictors of high risk for recurrence. A multivariate analysis performed by using the Cox's proportional hazard model showed that the schedule of instillation was an independent prognostic factor for reccurence. In the present study, only 2 patients showed progression and one patient died of UC. There was no adverse event that forced discontinuation of the therapy. In conclusion, epirubicin instillation influenced the prevention of recurrence, but the benefit of long-term period was not confirmed.

Molecular-targeted drugs are agents that act on molecules which are specifically expressed in cancer, or on molecules whose expression is increased in cancer compared to normal tissue, and suppress the growth, infiltration and metastasis of cancer while affecting normal tissue as little as possible by selectively impairing function in cancer tissue. The major molecular targets in cancer therapy include oncogene products, growth factors and their receptors, signal-transducing molecules, hormone receptors, cell cycle-related proteins, telomerase-related molecules, apoptosis-related molecules, angiogenesis-related molecules, anticancer drug resistance/sensitivity factors, transcription factors, and molecules related to infiltration and metastasis. This paper reports on the molecular-targeted drugs currently considered for bladder cancer.

Luteinizing hormone-releasing hormone agonist (LH-RH analogue) therapy, is one of the most widely used hormonal therapies. Recently, subcutaneous injection of a new long acting 3-month LHRH analogue depot has been developed. We investigated the adverse events induced by injection of an LH-RH analogue in 82 patients (median age was 75 year old, 59-87) using our questionnaire. Forty-eight and 34 cases had been administered leuprorelin acetate (LSR) and goserelin acetate (ZLA). The presentation rate of skin reaction was 8.8% (3/34) in the ZLA group and 14.6% (7/48) in the LSR group. There was no significant difference in rate of skin reaction between the LSR and ZLA group (p = 0.5113). Eight patients had induration (6 in LSR 2 in ZLA). We also present a case of subcutaneous granuloma formation at the injection site after using the three-month type preparation of leuprorelin acetate. We should be aware of the risk of skin reactions at the injection site and monitor carefully when using an LH-RH analogue.

A 60-year-old man was admitted to our department with a left renal artery aneurysm that was detected while performing an examination for dermatomyositis. A 3-dimensional image showed a saccular renal aneurysm whose diameter was 6 cm. He required operative intervention. Because of the location (near the renal hilum), selective transcatheter embolization using an interlocking detachable coil was performed for endovascular treatment. The postoperative course was uneventful. This method appears to be a good choice for the treatment of renal artery aneurysm, considering its safety and the likelihood of success.

We report a case of adrenal metastasis from renal cell carcinoma. A 52-year-old man was referred to our hospital for a left renal mass. A computed tomography revealed a left renal tumor. Liver cirrhosis and splenomegaly were observed. Blood tests revealed pancytopenia; platelet count was 2.5 x 10(4)/mm3. The patient was treated by partial splenic embolization (PSE) in an attempt to ensure a safe nephrectomy. After the embolization, his platelet count increased to 6.1 x 10(4)/mm3, and left nephrectomy was performed successfully. Histopathological finding was renal cell carcinoma (RCC). We concluded that PSE before surgery was useful for the patients with thrombocytopenia due to hypersplenism. Four years after surgery, computed tomography revealed the presence of a mass on the right adrenal gland. He was suspected of having a non-functioning adrenal tumor. Metastasis of the RCC was suspected and right adrenalectomy was performed by a laparoscopic procedure. Histologically, the mass was identified as a RCC metastasis. It is clinically rare for an RCC metastasis to the contralateral adrenal gland to occur.

We report a case of a patient with a fistula between the left ureter and abdominal aorta. The patient was a 44-year-old male who had undergone radiation therapy (intraoperative: 25 Gy, external beam: 50 Gy) and chemotherapy (CDDP: 250 mg) for retroperitoneal lymph node metastasis from seminoma. His postoperative course was complicated by stenosis of bilateral ureters, which were treated by indwelling double J-stents. Fifteen years after the operation, gross hematuria occurred from the left ureteral orifice when exchanging the left ureteral double J-stent. Computed tomographic scan demonstrated left ureteral-abdominal aortic fistula formation at the crossing point. Massive hemorrhage was suspected to have prompt fistula formation between the left ureter and the aorta. At exploration, there was a fistula of about 7 mm in diameter at the anterior surface of the aorta, and the stent was presumably inserted from it. The aortic fistula was successfully closed. In addition, the left ureter was ligated proximal to the fistula and percutaneous left nephrostomy were performed. His postoperative course was uneventful. We should be aware that uretero-arterial fistula can occur as a serious complication of ureteral catheter exchange after prolonged ureteral stenting and radiation therapy.

A 25-year-old man was admitted to our hospital because of left lumbago. An abdominal X-ray film demonstrated multiple calculi in the medullary positions of both kidneys and an impacted calculus in the left ureter. He was diagnosed with bilateral nephrocalcinosis and nerve deafness due to distal renal tubular acidosis (RTA) in childhood and was treated with alkali agents for several years. Extracorporeal shock wave lithotripsy was performed successfully against the left ureteral calculus. His older brother had also been diagnosed with RTA and nephrocalcinosis at the age of 2 years and 6 months. Nephrocalcinosis due to RTA associated with nerve deafness in brothers is rarely reported.

Congenital arteriovenous fistula(AVF) of the kidney is a rare condition. We report a case of renal AVF with chief complaints of macroscopic hematuria, and treated with transcatheter arterial embolization (TAE) using coils. The patient was diagnosed as having left renal AVF by Color Doppler ultrasound. The signs and symptoms disappeared after embolization. The clinical course of a case is reported and the literature is reviewed. Color Doppler ultrasound is required to give a definite diagnosis of renal AVF.

A 67-year-old female was referred to our hospital with the chief complaint of genital bleeding. Physical examination revealed a thumb's-head-sized tumor at the external urethral meatus. Histopathological examination of the biopsy specimen suggested papillary carcinoma. She underwent partial urethrectomy with negative surgical margins. The final pathological diagnosis of the tumor was papillary adenocarcinoma, of Stage A according to Grabstald's classification. She is alive with no evidence of recurrence at 5 months after surgery.

Surgical therapy is not only a therapeutic method but also an important procedure to provide useful information in determining a postoperative treatment strategy. Compared with postoperative cancer staging based on specimens obtained during surgery, more than 30% of cancers were inaccurately staged preoperatively, even when a current advanced diagnostic imaging technique was used. Compared with postoperative histological 30-40% of cancer staging were inaccurately staged based on a preoperative biopsy. These misstaging cases pose a significantly important problem. Approximately 15% and 30% of clinical stage C prostate cancers have been rated as pT2 and pN(+), respectively. Patients with pT3 prostate cancer who underwent radical prostatectomy had 5-year and 10-year overall survival rates of 82% and 67%, respectively, which were comparable to those in patients with pT2 prostate cancer (82% and 67%, respectively). However, patients with prostate cancer rated as pT4 and pN(+) had very poor outcomes with 5-year overall survival rates of 42.4% and 32.6%, respectively. Therefore, even in patients with stage C prostate cancer, surgical therapy should be recommended if no infiltration of adjacent tissue has been noted and the operation is applicable; and an optimal postoperative therapeutic strategy should be selected based on the accurate pathological staging and histological grading using postoperative pathological specimens. Such approaches will prevent unnecessary hormone therapy in patients with pT2 prostate cancer and prevent missing optimal timing for radical cure, as well as allowing appropriate therapy to be selected for patients with pT4 and pN(+) prostate cancer, for whom prognosis may be poor.

We report a case in a 70-year-old patient indicated to have a metastatic lesion from a chest X-ray taken during a medical examination. His blood prostatic specific antigen level was very high at 100 ng/ml (normal, less than 4.0 ng/ml). Palpation of the prostate disclosed enlargement to hen's egg size with an irregular surface and indurations bilaterally. Transrectal sextant needle biopsy of the prostate was performed, revealing moderately differentiated adenocarcinoma. Computed tomography (CT) scan and bone scintigraphy showed intrapelvic lymphnode adenopathy and metastasis to the right pubic bone. Under a diagnosis of stage D2 prostate cancer, we initiated endocrine therapy (luteinizing hormone-releasing hormone analogue depot every 4 weeks and bicalutamide). Androgen blockage was very effective and after 6 months, the PSA level had decreased markedly to below 0.2 ng/ml. Sixteen months later, pulmonary metastasis completely disappeared. He is currently free from recurrence and progressing well.

Primary tumor originated from ureteral stump following nephrectomy for benign disease is extremely rare. A 79-year-old male was referred to our department for asymptomatic macroscopic hematuria. He had undergone left simple nephrectomy for renal tuberculosis 52 years ago. Cystoscopic examination revealed a ureteral tumor on the residual ureteral orifice. Under the diagnosis of left ureteral stump tumor, which was subsequently enhanced on computer tomographic scan and magnetic resonance imaging, he received partial cystectomy and excision of the left ureteral stump. The histological examination revealed grade 2 to 3 urothelial carcinoma with muscle invasion (pT2). He received no adjuvant chemotherapy. He is now alive and free from recurrence 2 months post-operatively. This is the 21st case reported in the Japanese literature.

A 52-year-old male was admitted to our hospital complaining of orthostatic vertigo, fatigue and weight loss, who underwent right total nephrectomy for renal cell carcinoma(RCC) with curative operation 13 years ago (in 1992). Endoscopic examination revealed a submucosal tumor with erosion in the duodenum. The diagnosis made from the biopsy specimens was metastatic RCC in the duodenum. Abdominal CT scan revealed that his metastasis has spread to the pancreas. Five million units of interferon a was administered intramuscularly three times a week for 1 month. He received blood transfusions and palliative care. He died 5 months later because of disease progression. Metastases of RCC have been often reported in the lungs, the liver, and the bones, but rarely in the gastrointestinal tract. This is a very rare case of metastatic RCC in the duodenum, which was diagnosed 13 years after curative right nephrectomy. Since late recurrence is characteristic of renal cell carcinoma, careful long-term follow-up is needed. To our knowledge, this is the 19th case of duodenal metastasis from RCC reported in the literature.

A 17-year-old male was referred to our hospital with the chief complaint of right back pain. Cystoscopic examination revealed a papillary tumor on the posterior wall following detection on screening ultrasound examination revealed a tumor in the bladder. Transurethral resection of the bladder tumor was performed. Histological examination of the excised tumor revealed transitional cell carcinoma, grade 1, pTa. No recurrence has been observed for about 1 year postoperatively.

Bladder carcinoma with skin metastasis is extremely rare. We herein report a case of a bladder tumor with skin metastasis. A 68-year-old man was referred to our hospital with macroscopic hematuria. Cystoscopy revealed a trigone papillary tumor. Transurethral resection of bladder tumor (TURBT) was performed and the pathological diagnosis was transitional cell carcinoma (TCC), pT1, G3. Thereafter, he received several courses of TURBT, intravesical chemotherapy (pirarubicin, bacillus Calmette-Guerin and mitomycin C) and intra-arterial chemotherapy because of recurrence. Thirteen years later, he underwent total cystoprostatectomy with neobladder formation. Histological examination revealed muscle-invasive bladder cancer with a staging of T3bNOM0. Two years and three months later, multiple firm nodules with eruptions appeared on the skin in several regions; they were resected and the histological findings revealed TCC. This indicated metastatic spread from the primary bladder TCC. He received only supportive treatment during this period due to renal dysfunction. He died four months after the manifestation of the skin metastasis due to multiple metastases.

A 46-year-old man was admitted to our hospital complaining of macroscopic hematuria with dull pain in the right flank. Laboratory finding showed renal dysfunction and abdominal ultrasound sonograph revealed bilateral hydronephrosis (right > left). Retrograde pyelography showed left ureteral calculi and a filling defect in the middle portion of the right ureter. Renal function improved after bilateral single-J ureteral stent placement. Selective wash cytology of right renal pelvis was class II. Ureteroscopy demonstrated right ureteral obstruction with smooth-surfaced protruded tumor and cold cup biopsy was performed. Histopathological diagnosis was a fibroepithelial polyp but with no malignancy. In addition, left transurethral lithotripsy was performed under ureteroscopy. After the endoscopic examination, a double pigtail stent inserted into the right ureter. We performed conservative management by repeat urine cytologies and retrograde pyelography due to thrombocytopenia. The urine cytologies all proved negative and retrograde pyelography showed no abnormal changes. A ureteroscopic procedure is considered to be useful for the diagnosis of ureteral polyps. Transurethral resection of ureteral polyps with a ureteroscope is recommended for treatment.

A 65-year-old man visited our hospital with a complaint of a left inguinal mass. He had had a past history of tuberculosis. A left spermatic cord tumor was suspected. Left high orchiectomy was performed. The mass did not connect with the testis or epididymis. The removed mass measured 4 x 2 x 1.5 cm in size. Microscopic examination showed a granulomatous lesion with Langhans giant cells. Tuberculin skin test was moderately positive. From these findings we diagnosed the patient with tuberculosis in spermatic cord. Antituberculous chemotherapy was subsequently initiated. Two months after surgery, recurrence has not been found.

Renal cell carcinoma is a common renal malignancy in adults but it is extremely rare in children. An 8-year-old boy visited our hospital with the complaint of right abdominal palpable mass. Computed tomographic (CT) scan revealed a right renal multilocular cystic mass which displaced the normal renal parenchyma. A right radical nephrectomy was done and pathological findings revealed cystic renal cell carcinoma. He received postoperative therapy with the administration of alpha interferon and has been well with no evidence of recurrence nor metastasis during 8 months after surgery. To our knowledge this is the youngest case of cystic renal cell carcinoma reported.

A 21-year-old woman who had been injured in a traffic accident appeared with abdominal pain and macroscopic hematuria. Computed tomography (CT) performed 6 hours after the injury showed extravasation of contrast medium in the right retroperitoneal space. Retrograde pyelography (RP) showed the interruption of right ureter at the site of ureteropelvic junction. We performed an abdominal operation 15 hours after the injury under the diagnosis of right ureteral avulsion. We observed a completely separated right ureter at the ureteropelvic junction, and performed an end to end anastomosis. The patient was discharged three weeks after surgery, and has not had any problems for three years.

A 66-year-old man presented at our hospital with left back pain. Intravenous pyelography, computerized tomography and magnetic resonance imaging revealed ureteral tumors of the complete left double renal pelvis and the ureter. An endoscopic examination disclosed a papillary tumor from the left ureteral orifice of the lower pole of the kidney. A transurethral resection of the tumor was done, and the pathological features revealed transitional cell carcinoma (PTa, grade 2). A left nephroureterectomy and a partial cystectomy were also carried out; macroscopic examinations showed a non-papillary tumor on the middle portion of the left ureter originating from the upper pole of the kidney. Microscopic examinations revealed transitional cell carcinoma (PT3, grade 3, PL1, PV1). Adjuvant chemotherapy (M-VAC) was administered but discontinued because of severe side effects. Dispite recurrence with retro-peritoneal lymph node metastasis, the patient is alive and again undergoing M-VAC chemotherapy 22 months after the initial surgery. However, the evaluation of the chemotherapy was "no change".

We present a case report of von Hippel-Lindau disease associated with renal cell carcinoma and bilateral cystadenoma of the epididymis. A 26-year-old man appeared with painless tumors of the bilateral scrotal contents. Ultrasonography and other radiographic examinations including computed tomographic scan and dripinfusion pyelography showed multiocular tumors in the bilateral epididymis and a right renal tumor 3 cm in diameter. The tumors of the bilateral epididymis were surgically resected and of the right renal tumor enucleated. Histopathological examination revealed cystadenoma of the epididymis and renal cell carcinoma (clear cell carcinoma, G1, pT1a). He has not received adjuvant therapy, and is doing well with no evidence of metastatic disease 2 years after surgery.

Heparanase, which is an extracellular matrix degradative enzyme, degrades heparan sulfate and heparan sulfate proteoglycans, which are chief components of extracellular matrix and vascular basement membrane. The gene structure of this enzyme was recently determined. The biological functions of this enzyme in vivo were as follows: 1) this enzyme accelerates cancer cell invasion and metastasis though the degradation of vascular basement membrane and extracellular matrix by cancer cells; 2) this enzyme releases and activates heparin-binding growth factors such as bFGF and VEGF from heparan sulfate proteoglycans, and induces angiogenesis; 3) the degradative products of heparan sulfate proteoglycans by this enzyme suppress the biological function of activated T-lymphocytes. Therefore, heparanase is thought to be a favorable molecule for acceleration of cancer invasion and metastasis. The expression of heparanase is strongly correlated with the metastasis of melanoma and fibrosarcoma. Thus, heparanase may play important roles in invasion and metastasis of cancer.

A 76-year-old woman presented with dull pain in left flank. Excretory urogram showed no function of left kidney. Retrograde pyelography, ultrasonography, computed tomography and magnetic resonance imaging demonstrated hydronephrosis of the left kidney and a mass lesion surrounding the ureter. The tumor was removed together with the upper region of the left ureter and kidney. The tumor was 5 x 3 x 2.5 cm in diameter and the pathological diagnosis was a leiomyosarcoma. Although recurrent tumor arose in the pelvis at 14 months after the operation, the patient has been in good general condition without showing any other evidence of recurrent lesion. This case may indicate the importance of early resection of retroperitoneal leiomyosarcoma.