Yutaka Sugiyama

Pharmacological effects of solifenacin on human isolated urinary bladder.

To investigate the effects of solifenacin on human detrusor smooth muscles, we evaluate the effects of solifenacin on the contractions induced by carbachol, KCl, CaCl2 and electrical field stimulation (EFS), and the EFS-induced acetylcholine release from detrusor smooth muscle strips by using the muscle bath and microdialysis technique. The effects of solifenacin were also compared with effects of other antimuscarinic agents (atropine, oxybutynin and propiverine). Pretreatment with various antimuscarinic agents caused parallel shifts to the right of the concentration-response curves to carbachol. The pA2 value of the Schild plots for solifenacin was similar to that for oxybutynin. Atropine did not inhibit the KCl- and CaCl2-induced contractions, while solifenacin, oxybutynin and propiverine significantly inhibited these contractions. EFS-induced contractions were inhibited by various antimuscarinic drugs in a concentration-dependent manner. In the presence of atropine, solifenacin tended to inhibit the residual atropine-resistant contractions induced by EFS, but it was not significant. However, oxybutynin and propiverine inhibited them under the same conditions. Although pretreatment with atropine and propiverine did not cause significant changes in EFS-induced acetylcholine release, solifenacin and oxybutynin caused significant decreases in acetylcholine release. The present results suggest that solifenacin inhibits contractions of human detrusor smooth muscles mainly by the antimuscarinic action and that the high concentration of solifenacin has Ca2+ channel antagonist action. Moreover, solifenacin may block not only postjunctional receptors, but also prejunctional receptors to modulate acetylcholine releases in cholinergic nerve endings in human detrusor smooth muscles. The findings support that muscarinic-receptor-inhibitory actions in human bladder mainly contribute to the usefulness of solifenacin as a therapeutic drug for overactive bladder.

Pharmacological effects of propiverine and its active metabolite, M-1, on isolated human urinary bladder smooth muscle, and on bladder contraction in rats.

Objective:  To investigate the effects of M‐1, a major active metabolite of propiverine on the bladder.

Primitive neuroectodermal tumour of the kidney with spontaneous regression of pulmonary metastases after nephrectomy

A 23-year-old women was admitted complaining of a 7-month history of general fatigue, slight fever, right flank pain and gross haematuria. CT showed a a 13 ¥ 10 cm right renal mass (Fig. la) and several nodules in both lungs, suggesting multiple pulmonary metastases. CT and cavography revealed a filling defect in the right renal vein and the inferior vena cava (IVC), suggesting a tumour thrombus in both (Fig. la). Aortography showed the mass to be hypervascular (Fig. lb). She underwent radical nephrectomy with cavotomy under a diagnosis of metastatic RCC with IVC tumour thrombus. The pulmonary metastatic lesions decreased in size and number 14 days after surgery (Fig. 1c) and subsequently increasingly regressed with time. At 2 months after surgery they had completely regressed (Fig. 1d) . Before surgery her urinary excretion of homovanillic acid (HVA) and vanillylmandelic acid (VMA) were 3.3 and 3.3 mg/day (within the normal ranges; HVA 1.5–6.6 mg/day; VMA 1.3–5.1 mg/day). The histological findings of the resected tumour showed the typical small round to ovoid tumour cells and several neuroblastic Homer Wright rosettes, suggesting the tumour to be a primitive neuroectodermal tumour (PNET) or neuroblastoma (Fig. 2a). Positive reactions were obtained with the antibodies against synaptophysin, neurone-specific enolase, S100 protein and CD99 (MIC2) [1] (Fig. 2b) but not to chromogranin and neurofilament. Taken together, the histological findings and laboratory results suggested a diagnosis of PNET of the kidney. The resection of the primary lesion was probably responsible for the complete regression of the pulmonary metastases. The patient remains well 1 year after surgery.

Isolated Renal Tuberculosis following Intravesical Bacillus Calmette-Guérin Therapy for Bladder Cancer

We present a case of isolated renal tuberculosis following bacillus Calmette-Guérin (BCG) therapy for bladder cancer. In the presurgical radiographic examination, we suspected an atypical renal cell carcinoma. According to the diagnosis of renal cell carcinoma, we performed a radical nephrectomy. The histological findings were tuberculosis-specific inflammatory changes and the patient received an antituberculous multiple drug therapy for a year. It is concluded that we should pay attention to the possibility of a renal tuberculosis granuloma in any patient who presented with subacute formed renal masses following BCG treatment before deciding on the strategy of the treatment of the renal masses, especially in patients who had received such a treatment which induced an immunocompromised state.

CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis

CD169+ macrophages are suggested to play a pivotal role in establishing anti‐tumor immunity. They capture dead tumor cell‐associated antigens and transfer their information to lymphocsytes, including CD8+ T cells, which is important for successful tumor suppression. This study aimed to determine the prognostic significance of CD169+ macrophages residing in the tumor‐draining lymph nodes from cases of bladder cancer. In this retrospective study, 44 bladder cancer patients who received radical cystectomy were examined. The abundance of CD169+ macrophages in the regional lymph nodes and the number of CD8+ T cells in the primary tumor were investigated by immunohistochemistry. A CD169 score was calculated based on the intensity of CD169 staining and the proportion of CD169+ macrophages, and the scores were compared to the patients’ clinicopathological parameters. A high CD169 score was significantly associated with low T stage and with a high number of CD8+ T cells infiltrating into the tumor. The group with high CD169 expression had significantly longer cancer‐specific survival than the group with low CD169 expression (5‐year cancer‐specific survival rate: 83.3% vs 31.3%). In a multivariate analysis, the CD169 score was identified as a strong and independent favorable prognostic factor for cancer‐specific survival. Our findings suggest that CD169+ macrophages in the lymph nodes enhance anti‐tumor immunity by expanding CD8+ T cells in bladder cancer. The CD169 score may serve as a novel marker for the evaluation of bladder cancer prognosis.

Phenotypical change of tumor-associated macrophages in metastatic lesions of clear cell renal cell carcinoma

Macrophages are the main immune cells of the tumor microenvironment in clear cell renal cell carcinoma (ccRCC). A high density of CD163+ or CD204+ tumor-associated macrophages (TAMs), rather than the density of total TAMs, is known to be linked to poor clinical outcome. In the present study, we investigated the phenotypical differences between the paired primary and metastatic lesions in ccRCC cases. Using immunostaining, the densities of CD163+ and CD204+ TAMs in metastatic lesions were found to be significantly lower compared to primary lesions, although the total number of TAMs was increased in metastatic lesions. Since CD163 and CD204 are considered to be the markers of an M2/protumor phenotype in macrophages, TAMs in metastatic lesions are suggested to have a greater M1/inflammatory function compared with those from primary lesions. These findings give new insights in regard to the immunological status of metastatic lesions of ccRCC.

Role of bone scan index in the prognosis and effects of therapy on prostate cancer with bone metastasis: Study design and rationale for the multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index (PROSTAT-BSI) stu

To present the study design and rationale of Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index, a prospective study aiming to determine the role of the bone scan index, the amount of bone metastasis, in the treatment and prognosis of prostate cancer patients.

Advanced prostate cancer discovered with cancerous peritonitis: Case report

Cancerous peritonitis occurs rarely in patients with prostate cancer since prostate cancer is not likely to cause peritoneal dissemination because of the localization of prostate itself and the low frequency of metastasis to the intraperitoneal organs from prostate cancer. This rarity of cancerous peritonitis may delay the diagnosis and treatment of prostate cancer. Herein we report a case of a patient with abdominal distension due to cancerous peritonitis wherein the primary tumor in the intraperitoneal organs could not be detected, but prostate cancer was diagnosed by the presence of adenocarcinoma cells using ascites puncture cytology.