Probe-Based Confocal Laser Endomicroscopy Using Acrinol as a Novel Dye Can Be Used to Observe Cancer Nuclei of Bladder Carcinoma In Situ.

Background: Cystoscopy using white light is a standard procedure for diagnosing bladder cancer; however, white light can result in missed lesions that are present, but not visible, such as in cases of carcinoma in situ (CIS). In this case report, we describe observing the nuclei of urothelial carcinoma cells in situ that were not visible with cystoscopy under white light using probe-based confocal laser endomicroscopy (pCLE) with acrinol and fluorescein during transurethral resection of a bladder tumor (TURBT). Case Presentation: A 59-year-old male with a medical history of neurogenic bladder dysfunction with multiple bladder diverticula was referred to the urology department for gross hematuria. TURBT was performed with the assistance of pCLE, using acrinol as a novel dye. Standard cystoscopy under white light could not detect any bladder tumor; however, pCLE using acrinol could detect the abnormal nuclei of bladder CIS. Subsequent histopathologic analysis of the specimen confirmed a diagnosis of bladder CIS. To our knowledge, this is the first reported case of bladder CIS diagnosed with the assistance of pCLE using acrinol in a patient undergoing a TURBT. Conclusion: pCLE using acrinol as a novel dye can help observe the cancerous nuclei of bladder CIS that cannot be detected using conventional cystoscopy under white light. Therefore, pCLE using acrinol is one possible modality for performing an optical biopsy during TURBT.

Measurement of postvoid residual urine in conscious mice using high-frequency transrectal ultrasound.

The aim of this study was to develop a novel technique for a minimally invasive ultrasound measurement of postvoid residual urine (PVR) in conscious mice using a miniature ultrasound probe and a transrectal approach. The PVR was determined by the ellipsoid formula in the maximum sectional image of the bladder visualized with a 20-MHz ultrasound probe (2 mm in diameter) inserted into the rectum. The accuracy, including the intra- and interobserver reproducibilities, of the ultrasonic PVR measurements (in 10 5- to 50-week-old mice) was evaluated, which revealed excellent internal consistency. In M(3) muscarinic acetylcholine receptor knockout male mice, a chronological evaluation of the PVR identified abnormal urinary retention present at infancy and exacerbated with aging, suggesting significant voiding dysfunction. Our technique for the measurement of PVR in conscious mice was accurate and useful for identifying the voiding dysfunction in mice.

Enhancement of the sensitivity of renal cell carcinoma cells to fas-mediated cytotoxicity and apoptosis by the selective cyclooxygenase-2 inhibitor JTE-522.

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the production of prostaglandins and its inhibitors have been shown to induce apoptosis in a variety of cancer cells. We reasoned that combination treatment of renal cell carcinoma (RCC) cells with COX-2 inhibitors and anticancer agents may result in synergistic apoptosis. We examined whether the selective COX-2 inhibitor JTE-522 synergizes with anticancer agents in cytotoxicity and apoptosis against RCC cells. METHODS: The cytotoxicity of the selective COX-2 inhibitor JTE-522 and other anticancer agents against the RCC cell lines and the normal renal cell line was determined by the microculture tetrazolium dye assay. RESULTS: JTE-522 was cytotoxic against the Caki-1 RCC cell line. JTE-522 and anti-Fas monoclonal antibody (CH-11) exhibited a synergistic cytotoxic effect against Caki-1 cells. In contrast, JTE-522 in combination with 5-fluorouracil, adriamycin, cis-diamminedichloroplatinum, or interferon-alpha, all commonly used clinically, resulted in an additive cytotoxic effect. Synergy achieved in cytotoxicity with JTE-522 and CH-11 was shown to be due to apoptosis. CONCLUSIONS: The present study demonstrated that the selective COX-2 inhibitor JTE-522 had a cytotoxic effect on RCC and that synergistic cytotoxicity against RCC was obtained with JTE-522 in combination with anti-Fas monoclonal antibody. These results suggest that selective COX-2 inhibitors in combination with immunotherapy may be useful in treating patients with RCC.

Significant antitumor activity of cationic multilamellar liposomes containing human interferon-beta gene in combination with 5-fluorouracil against human renal cell carcinoma.

Immunotherapy is one of the most effective treatments against metastatic renal cell carcinoma (RCC). However, the response rate is not high. Therefore, more effective therapies are necessary for patients with metastatic RCC. We previously reported on the significant antitumor activity of cationic multilamellar liposome containing human interferon-beta (huIFN-beta) gene (IAB-1) against RCC. We then examined the antitumor effect of IAB-1 in combination with anticancer drugs against RCC. The cytotoxicity of IAB-1 alone, and in combination with anticancer drugs, cisplatin, adriamycin, 5-fluorouracil, gemcitabine, paclitaxel and irinotecan hydrochloride against the human RCC cell line NC65 was examined by the colorimetric method using tetrazolium salt. For the in vivo study, we used NC65 cells inoculated into the severe combined immunodeficiency mouse. The results showed that the in vitro combination therapy with IAB-1 and 5-FU was more cytotoxic than IAB-1 alone. However, synergistic cytotoxicity was not observed when combined with IAB-1 and other anticancer drugs. NC65 tumors transfected with IAB-1 in mice were smaller than those receiving an injection of empty liposome or the recombinant huIFN-beta protein. Treatment with IAB-1 in combination with 5-FU resulted in significant anticancer activity. IAB-1 enhanced the activity of thymidine phosphorylase (TP), which converts 5-FU to the active metabolite, FdUMP. In contrast, IAB-1 decreased the activity of thymidylate synthase (TS), which is a target enzyme of 5-FU. In conclusion, these findings indicate that a combination of IAB-1 and 5-FU may have enhanced antitumor activity against human RCC, suggesting its potential clinical application. The mechanism of enhanced cytotoxicity by combination therapy with IAB-1 and 5-FU may up-regulate TP activity and down-regulate TS activity.

[A case of primary adenocarcinoma of the epididymis].

A 68-year-old man presented with right intrascrotal swelling. On palpation, a hard tumor without pain was recognized at the head of the right epididymis. Power Doppler ultrasonography revealed blood flow signals within the tumor. Surgical exploration was performed under the tentative diagnosis as possible malignant tumor of the epididymis. The right epididymis adhered to the testis so strongly, that the epididymis was resected with the testis. Pathological diagnosis was moderately differentiated adenocarcinoma of the epididymis. The results of general examinations on possible presence of primary lesions in other organs were all negative. Finally, the diagnosis of primary adenocarcinoma of the epididymis was obtained. He remains free of disease 17 months after surgery.

Acute urethritis caused by Neisseria meningitidis.

A 48-year-old heterosexual Japanese man visited the outpatient clinic of Nagoya Urology Hospital, complaining of burning pain at voiding and pus discharge from the urethral orifice. These symptoms appeared the day following oral-genital contact (fellatio) with a commercial sex worker. On the basis of the presumptive clinical diagnosis of gonorrhea because of the microscopic detection of diplococci in the urethral discharge, he was treated with levofloxacin (300 mg per day) for 7 days. His symptoms responded quickly and urinalysis taken 7 days later was normal. Microbiological examinations isolated Neisseria meningitidis in the urethral discharge by culture with the use of enzymatic profiles. Further prevalence of sexually transmitted diseases (STD) through oral-genital contact would lead to an increase in meningococcal urethritis.