Ryosuke Noguchi

Urinary nuclear matrix protein 22 as a new marker for the screening of urothelial cancer in patients with microscopic hematuria.

Purpose: The aim of the present study was to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a new urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology.

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection

BackgroundIn a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT).MethodsThe subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group).ResultsAmong the 156 patients, who were monitored for 11–26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P ≪ 0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0 U/ml for NMP22 and 6.0 ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively.ConclusionsBecause the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0 U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.

Intra-Arterial Chemotherapy for Bladder Cancer by Insertion of Catheter from Inferior Gluteal Artery

Thirty-four patients with locally advanced bladder cancer have been treated with selective intra-arterial infusion of CDDP and/or ADM (IA therapy) prior to planned surgical resection. Follow-up ranged from 25 to 108 months (median 61). Initial tumor stage was cT2 in 10 patients, cT3 in 19 and cT4a in 5. Catheterization technique: gluteal muscles were dissected gently along the muscle fiber to expose the inferior gluteal artery with the patients in prone position, then the catheter was inserted. The tip was wedged in the internal iliac artery below the bifurcation of the superior gluteal artery. ADM 10-20 mg and/or CDDP 10-20 mg were infused once or twice a week. Total dose of ADM and CDDP were 40-580 and 60-240 mg. Thirteen patients received IA therapy + hyperthermia and 8 IA therapy + irradiation. Surgical resection included total cystectomy (22 patients), partial cystectomy (3 patients) and transurethral resection of the prostate (5 patients). Survival rate at 5 years is 57.9% (T2 = 90.0, T3 = 52.1, T4 = -). Eighteen patients are alive with no evidence of recurrences, and 11 patients were free of disease for more than 5 years. Side effects were bone marrow suppression (5 patients), vomiting (4), erosion of gluteal skin (7), and neurotoxicity, such as sensory disturbance in lower extremities or ischialgia (2); treatment was well tolerated in others. In conclusion, our results suggest that intra-arterial infusion of ADM and/or CDDP by insertion of catheter from inferior gluteal artery is safe with minimal systemic side effects, and prolongs survival for invasive bladder cancer.

Evaluation of the invasive potential of superficial bladder cancer by adenosine triphosphate measurement

In order to predict the malignant potential of superficial bladder cancer, in 121 patients with this malignancy adenine nucleotide levels (adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate) and energy charge in bladder cancer cells were determined. The nucleotides were analyzed according to the method of Bücher, and the energy charge was calculated by applying the formula of Atkinson. It was clearly pointed out that superficial bladder tumors, which became invasive and/or metastatic, had higher levels of adenylate compounds than those which became not. Our results show that a high correlation exists between adenine nucleotide content and tumor progression.

Intra-arterial chemotherapy for bladder cancer.

SummaryIntra-arterial infusion chemotherapy with adriamycin (ADM) was carried out in 32 patients with bladder cancer prior to total cystectomy. An oblique incision approximately 12 cm long was made in the gluteal region to expose either the superior or inferior gluteal artery, into which a Teflon catheter was inserted and fixed. The distal end of the catheter was taken out from under the skin in the precordial region. Via this catheter, a single dose of 10 mg ADM was injected twice a week. Superior-gluteal-artery infusion chemotherapy was performed in 7 patients; the 5-year survival rate was 14.3%, which was not as high as expected. Inferior-gluteal-artery infusion chemotherapy was performed in 25 patients. Cisplatin (CDDP) was used with ADM in 8 patients. Radiation and/or hyperthermia were used i n11 patients. The 5-year survival rate in these 25 patients was 58.4%, which was considered to be satisfactory. Of these 25 patients, 5 were stage-T4 cases; for these, the treatment was ineffective, and all 5 died within 2 years. Of the 6 patients at stage T2, 1 died, as did 1 patient with carcinoma in situ (CIS). Of the 13 patients with bladder cancer at stage T3, 3 died; lymph-node metastases were found in all 3 of these cases. Of the 25 patients who received inferior-gluteal-artery infusion chemotherapy, 9 died of cancer; all 9 died within 2 years due to distant metastases. There was no evidence of recurrence in any patient who survived for 2 years or more after total cystectomy. Therefore, inferior-gluteal-artery infusion chemotherapy may be effective as a preoperative adjuvant therapy with no serious side effects.

[alpha-Interferon therapy in a patient with renal cell carcinoma and renal hypofunction].

A 60-year-old man who had renal cell carcinoma with renal hypofunction underwent partial nephrectomy followed by alpha-interferon therapy (LHBI 3 x 10(6) IU/day intramuscular injection for 4 weeks, then twice a week for 6 months). Glomerular filtration rate slightly decreased to 28. 5 from 32.6 ml/m after partial nephrectomy. On single injection of IFN, its serum level reached the maximum of 20.3 IU/ml, at 12 hours of injection, and 10.4 IU/ml at 24 hours. After 4 weeks, that was 50.6 IU/ml. NK activity and ADCC which were 32, and 68%, respectively before treatment, reduced to 6, and 28%, respectively after 4 weeks. After maintenance therapy they were shown to rise up to 26, and respectively 73%, and increased immunoactivity was confirmed.