Transarterial chemoembolisation for palliative treatment of renal cell carcinoma in two dogs with pulmonary metastasis.

Two dogs with anorexia and rapid weight loss were referred to our hospital due to a right renal mass and several pulmonary nodules. Both dogs underwent needle core biopsy of the mass, followed by transarterial chemoembolisation of the renal mass. A catheter was inserted from the femoral artery and advanced into the right renal artery. A suspension of carboplatin (100 mg/m2 ) and equivalent lipiodol was administered via the inserted multipurpose catheter. Immediately after, under fluoroscopic guidance, pulse injections of small amounts of gelatin particles (diameter 1 mm) dissolved in iohexol were administered until complete embolisation of the renal artery. Histopathologic diagnosis was renal cell carcinoma in both dogs. Clinical signs improved for 134 and 358 days after transarterial chemoembolisation. In addition, postoperative radiographs demonstrated a decrease in the tumour size. The dogs died 215 and 525 days after the initial evaluation, respectively. As a palliative treatment, transarterial chemoembolisation might help reduce the tumour volume and improve the quality of life in dogs with renal cell carcinoma and distant metastases.

Intraoperative identification of canine hepatocellular carcinoma with indocyanine green fluorescent imaging.

OBJECTIVES: To evaluate the feasibility of high-sensitivity near-infrared fluorescence imaging with indocyanine green for intraoperative identification of hepatocellular carcinoma in dogs. METHODS: Twelve hepatic nodules were surgically resected from six dogs. In each dog, 0 · 5 mg/kg indocyanine green was intravenously injected for 12 to 18 hours preoperatively. The hepatic nodules were investigated under laparotomy using a near-infrared fluorescence imaging light camera system prior to resection. Resected nodules were histopathologically diagnosed and their fluorescence images were evaluated. RESULTS: Of the 12 hepatic nodules, 6 were diagnosed as hepatocellular carcinoma and 6 as nodular hyperplasia. Indocyanine green-fluorescence was observed in four large hepatocellular carcinoma nodules and one case of nodular hyperplasia, whereas it was absent in the remaining nodules. The sensitivity and positive predictive values of indocyanine green fluorescent imaging for hepatocellular carcinoma was 71 · 4 and 80 · 0%, respectively. Complete resection of the hepatic masses was achieved in all dogs. CLINICAL SIGNIFICANCE: Near-infrared fluorescence imaging may be feasible for intraoperative mapping of hepatocellular carcinomas in hepatic lobes and may help increase the chance of complete resection of hepatocellular carcinoma in dogs.

[Staged operation of off-pump coronary artery bypass grafting using aortic connector system, and concomitant surgery for abdominal aortic aneurysm and gastric cancer; report of a case].

Recently the patient of the atherosclerotic disease associated with malignant disease has been increased. A 75-year-old man was referred to our section with an infrarenal abdominal aortic aneurysm (AAA) and a gastric cancer (GC). Preoperative coronary angiogram revealed the significant stenoses of the right coronary and the left anterior descending coronary artery. We selected the staged operation of off-pump coronary artery bypass grafting (CABG) [OPCAB] and the concomitant surgery for the AAA and the GC. Operative invasion could decrease with the surgical procedure of the OPCAB and the concomitant surgery compared to the conventional CABG or the separate operation. We used the aortic connector system during OPCAB to prevent such the serious complications of the aortic dissection or the systemic embolism due to the calcified ascending aorta.

[The ischemic mitral valve regurgitation due to acute coronary thromboembolism; report of a case].

A 71-year-old man with congestive heart failure due to acute myocardial infarction was referred to our hospital. He was under the support of mechanical ventilation and the intraaortic balloon pumping (IABP) and coronary angiogram revealed the thromboembolism of the obtuse marginal artery. We completed the revascularization by the direct percutaneous coronary intervention. However, grade II mitral valve regurgitation and heart failure were worsening. Mitral valvuloplasty and the modified maze procedure through the partial lower sternotomy were performed. He is still in good condition 4 years later. Ischemic mitral valve regurgitation due to the coronary thromboembolism is very rare. Careful follow-up on the grade of ischemic mitral valve regurgitation is necessary even after the early coronary recanalization. The surgical approach of the partial sternotomy should be used in such a case of acute mitral valve regurgitation.

Significance of dihydropyrimidine dehydrogenase activity in renal cell carcinoma.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the pathway of uracil and thymine catabolism. DPD is also the principal enzyme involved in the degradation of 5-fluorouracil (5-FU), an anticancer chemotherapeutic agent that is used clinically to treat renal cell carcinoma (RCC). Little is known about the significance of DPD activity in human cancers. We investigated the activity of DPD in 68 RCC and the relationship between DPD activity and the sensitivity to 5-FU. The levels of DPD activity in RCC and normal kidney samples were determined by the 5-FU degradation assay. The sensitivity to 5-FU was assessed by the microculture tetrazolium dye assay. The activity of DPD was approximately 2-fold higher in normal kidney compared with RCC. DPD activity in Stage I/II RCC was approximately 2-fold higher than that in Stage III/IV RCC. The levels of DPD activity in Grade 1 and Grade 2 RCC were 3 and 2-fold higher, respectively, than that in the Grade 3 cancers. There was an inverse correlation between DPD activity in RCC cells and their sensitivity to 5-FU. Furthermore, 5-chloro-2,4-dihydroxypyridine (CDHP), a potent DPD inhibitor, enhanced the sensitivity to 5-FU. The current study is the first to demonstrate that the level of DPD activity was inversel correlated with both the progression of the disease and increased grade of RCC, and that DPD activity was inversely associated with the sensitivity of RCC to 5-FU, which was enhanced by a DPD inhibitor. These results suggest that a low DPD activity may be associated with the malignant potential of RCC. In addition, it may be possible to overcome 5-FU resistance by using DPD inhibitors in the treatment protocols of 5-FU-based chemotherapy for RCC.

Clinical evaluation of Ramosetron injections in the treatment of cisplatin-induced nausea and vomiting.

A phase III, double-blind, placebo-controlled study was performed to examine the safety and efficacy of ramosetron in cancer patients with cisplatin-induced nausea/vomiting. Patients were divided into two groups: group R received 0.3 mg ramosetron intravenously and group P received placebo. Eighty-eight patients were enrolled, 44 in each group; 84 (43 in group R, 41 in group P) were included in the clinical efficacy analysis and 86 (44 in group R, 42 in group P) in the safety analysis. Ramosetron was significantly more clinically effective than placebo against nausea, vomiting and anorexia; 65.1% of patients in group R experienced no vomiting in the first 6 h of observation compared with 7.3% of those receiving placebo. No serious adverse reactions or significant differences in safety were observed between the groups. Based on these results, ramosetron injection is effective in the treatment of cisplatin-induced nausea/vomiting and its clinical usefulness is demonstrated here.

Potentiation of the sensitivity of renal cell carcinoma cells to TRAIL-mediated apoptosis by subtoxic concentrations of 5-fluorouracil.

Cytotoxic chemotherapy has shown little antitumour activity against renal cell carcinoma (RCC). Although immunotherapy is relatively effective against RCC, the response rate is approximately 20%. Therefore, there is an urgent need to increase this response rate. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo-2L) is one member of the tumour necrosis factor ligand family that selectively induces apoptosis of cancer cells. Since several cytotoxic anticancer drugs including 5-fluorouracil (5-FU) also mediate apoptosis, we reasoned that combined treatment of cancer cells with TRAIL and drugs might result in synergy and overcome the resistance of the cancer cell. This study has examined whether TRAIL can synergise with 5-FU in both cytotoxic and apoptotic assays against drug-resistant RCC cells. Cytotoxicity was determined by an 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. Treatment of Caki-1 cells with TRAIL in combination with 5-FU resulted in a synergistic cytotoxic effect. Synergy was also achieved in freshly derived RCC cells from 3 patients. The enhanced cytotoxicity was obtained irrespective of the sequence of the treatment, but the highest cytotoxicity was observed when Caki-1 cells were treated with TRAIL and 5-FU simultaneously. The synergy achieved in cytotoxicity with TRAIL and 5-FU was shown to be due to apoptosis. The mechanisms responsible for the synergistic cytotoxicity and apoptosis were examined. Treatment of Caki-1 cells with 5-FU enhanced the expression of p53 and bax, but had no effect on the expression of bcl-2. Incubation of Caki-1 cells with TRAIL enhanced the intracellular accumulation of 5-FU and 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). Treatment of Caki-1 cells with TRAIL downregulated the expression of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) modestly, and upregulated the expression of orotate phosphoribosyltransferase (OPRT). However, the expression level of thymidine phosphorylase (TP) was not affected by TRAIL. This study demonstrates that combined treatment of RCC cells with TRAIL and 5-FU overcomes their resistance. The sensitisation obtained with freshly isolated RCC cells required low subtoxic concentrations of 5-FU. These findings support the potential application in vivo of a combination of TRAIL and 5-FU in the treatment of TRAIL/5-FU-resistant RCC.

Prognostic significance of thymidylate synthase activity in bladder carcinoma.

BACKGROUND: 5-fluorouracil (5-FU) is an anticancer agent clinically used against various cancers including bladder carcinoma. 5-FU inhibits thymidylate synthase (TS) and blocks DNA synthesis. TS is the key enzyme in the catalysis of the methylation from deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate. Little is known about the significance of TS in bladder carcinoma. The authors investigated the activity of TS in 82 bladder cancers and prognostic significance of the levels of TS and/or activities of dihydropyrimidine dehydrogenase (DPD), an important enzyme in the degradation of 5-FU. METHODS: The levels of TS and DPD activities in nonfixed, fresh, frozen, bladder carcinoma and normal bladder specimens were determined biochemically by the FdUMP binding assay and the 5-FU degradation assay, respectively. RESULTS: The activity of TS was 10-fold higher in bladder carcinoma compared with normal bladder. TS activity in muscle-invasive bladder carcinoma was threefold higher than that in Ta and T1 cancer. In addition, the activity of TS in T1 bladder carcinoma was threefold higher than that in Ta cancer. The level of TS activity in Grade 3 bladder carcinoma was 4.5-fold and 3.5-fold higher than that in Grade 1 and Grade 2 cancers, respectively. Patients with Ta and T1 bladder carcinoma with low TS activity had a longer postoperative tumor-free period than those with high activity in the 2-year follow-up. Patients with Ta and T1 bladder carcinoma with high or low TS activity were divided into four subgroups: high or low DPD activity subgroups. Patients with low TS activity and high DPD activity had the longest postoperative disease-free period among the 4 subgroups during the 2-year follow-up. CONCLUSIONS: To the authors' knowledge, the current study is the first study that demonstrated that the level of TS activity correlates with both the progression of the stage and the increase of the grade of bladder carcinoma and that elevated TS activity predicts early recurrence in Ta and T1 bladder carcinoma. These results suggested that elevated TS activity might have been associated with a higher chance of progression and recurrence of bladder carcinoma in the patients who participated in this study.

Significance of serum soluble Fas ligand in patients with bladder carcinoma.

BACKGROUND: The interaction of Fas and Fas ligand (FasL) plays an important role in cytotoxic T-lymphocyte-mediated and natural killer cell-mediated apoptosis against tumor cells. Circulating soluble FasL (sFasL) has been suggested to provide protection from Fas-mediated apoptosis. The current study examined this possibility in patients with bladder carcinoma. METHODS: The levels of sFasL in the serum of 163 patients with bladder carcinoma were determined using an enzyme-linked immunoadsorbent assay. Antiautologous tumor cytotoxic activity was assessed by the 12-hour chromium isotope ((51)Cr) release assay. RESULTS: The mean serum level of sFasL in patients with bladder carcinoma was 2.5-fold higher than that in healthy donors. The level of serum sFasL in patients with muscle-invasive bladder carcinoma was 2.5-fold higher than that in patients with superficial bladder carcinoma. In addition, serum sFasL levels in patients with T1 and Tis bladder carcinoma was 2-fold and 2.7-fold higher, respectively, than levels in patients with Ta bladder carcinoma. The serum level of patients with sFasL in Grade 3 bladder carcinoma were 2.4-fold and 1.7-fold higher than that in patients with Grade 1 and Grade 2 bladder carcinoma, respectively. Patients with Ta bladder carcinoma with a low level of serum sFasL (less than the median value) had a longer postoperative tumor-free interval than patients with a high sFasL level (greater than the median value) in the 5-year follow-up. There was an apparent inverse correlation between the level of serum sFasL and antiautologous tumor cytotoxic activity. CONCLUSIONS: The results of the current study demonstrated that the level of serum sFasL is correlated with both disease progression and increase in the tumor grade, and that an elevated serum sFasL level predicted early recurrence in patients with Ta bladder carcinoma. These findings suggest that elevated serum sFasL levels might be associated with a greater risk of disease progression and recurrence in patients with bladder carcinoma.

The significance of dihydropyrimidine dehydrogenase (DPD) activity in bladder cancer.

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the pathway of uracil and thymine catabolism. DPD is also the principal enzyme involved in the degradation of 5-fluorouracil (5-FU), which is one of the anticancer chemotherapeutic agents currently used in the treatment of bladder cancer. Little is known about the significance of DPD activity in human cancers. We investigated the activity of DPD in 74 bladder cancers and the relationship between the DPD activity and the sensitivity to 5-FU. The levels of DPD activity in bladder cancer and normal bladder tissues were determined by the 5-FU degradation assay. The sensitivity to 5-FU was assessed by the microculture tetrazolium dye (dimethylthiazolyl-2-5-diphenyltetrazolium bromide; MTT) assay. The activity of DPD was approximately 2-fold higher in bladder cancer tissues compared with normal bladder tissues. DPD activity in invasive bladder cancers was approximately 2-fold higher than that in superficial cancers. In addition, the levels of DPD activity in grade 2 and grade 3 bladder cancers were approximately 3-fold and 4-fold higher than that in grade 1 cancers, respectively. Patients with superficial bladder cancer with a low DPD activity had a slightly longer postoperative tumour-free period than those with a high DPD activity over a 2-year follow-up period, but this was not significant. There was an inverse correlation between DPD activity in bladder cancer cells and their sensitivity to 5-FU. Furthermore, 5-chloro-2,4-dihydroxypyridine (CDHP), a potent DPD inhibitor, enhanced the sensitivity to 5-FU. The present study has demonstrated that the level of DPD activity correlated with the progression of the stage and an increase in the grade of the bladder cancer. These results suggest that an elevated DPD activity might be associated with the malignant potential of the bladder cancer. In addition, it might be possible to overcome 5-FU insensitivity by using DPD inhibitors in the treatment protocols of 5-FU-based chemotherapy for bladder cancers.

Arterial remodeling influences the development of intimal hyperplasia after stent implantation.

OBJECTIVES: We examined whether preinterventional arterial remodeling influenced the interventional results after stenting. BACKGROUND: Arterial remodeling is seen in atherosclerotic lesions, and it may play an important role in the early stage of atherosclerosis. METHODS: We examined 113 lesions that underwent elective stenting using tubular slotted stents under intravascular ultrasound guidance. The lesions were divided into three groups--adequate, intermediate and inadequate remodeling group--according to preinterventional arterial remodeling. The patients were subjected to coronary angiography and intravascular ultrasound evaluation on average 6.4 months after stenting. RESULTS: At baseline and immediately after stenting, there were no differences in quantitative angiographic analysis among remodeling groups. However, the plaque cross-sectional area (CSA) in the minimal lumen CSA at preintervention and intimal hyperplasia CSA at follow-up were significantly larger in the adequate remodeling group than in the inadequate remodeling group. The restenosis rate of stenting for the lesions with inadequate arterial remodeling was very low (9.4%). A significant positive correlation was found between preinterventional plaque CSA and intimal hyperplasia CSA at follow-up (r = 0.47, p < 0.0001). Moreover, remodeling index significantly correlated with relative intimal hyperplasia CSA (r = 0.28, p < 0.01). CONCLUSIONS: Preinterventional arterial remodeling influenced the development of intimal hyperplasia after stenting.

Enhanced sensitivity of bladder cancer cells to tumor necrosis factor related apoptosis inducing ligand mediated apoptosis by cisplatin and carboplatin.

PURPOSE: The development and acquisition of multiple drug resistance in cancer cells are a consequence of cancer chemotherapy and remain a major obstacle in treatment. Therefore, there is an obvious need for alternative approaches, such as immunotherapy and gene therapy. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is one of the tumor necrosis factor ligand families and it selectively induces apoptosis against cancer cells. Several cytotoxic anticancer drugs also mediate apoptosis and may share the common intracellular pathways leading to apoptosis. We reasoned that combination treatment of cancer cells with TRAIL and drugs may overcome this resistance. We evaluated whether bladder cancer cells are sensitive to TRAIL mediated cytotoxicity and whether TRAIL may synergize with anticancer agents in cytotoxicity and apoptosis against bladder cancer cells. MATERIALS AND METHODS: Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. RESULTS: Human T24 bladder cancer line was relatively resistant to TRAIL and TRAIL was not cytotoxic against normal bladder cells. Treatment of T24 cells with TRAIL in combination with 5-fluorouracil or mitomycin C did not overcome resistance to these agents. However, treatment of T24 cells with a combination of TRAIL and cisplatin resulted in a synergistic cytotoxic effect. Synergy was also achieved in the cisplatin resistant T24 line (T24/CDDP), 2 other bladder cancer lines and 3 freshly derived bladder cancer cells. The combination of TRAIL and carboplatin resulted in a synergistic cytotoxic effect on T24 cells. However, the combination of TRAIL and trans-diamminedichloroplatinum (II) resulted in an antagonistic cytotoxic effect. The synergy achieved in cytotoxicity with TRAIL and cisplatin was also achieved in apoptosis. Treating T24 cells with cisplatin enhanced the expression of bax but not bcl-2. Incubation of T24 cells with TRAIL increased the intracellular accumulation of cisplatin. CONCLUSIONS: This study demonstrates that combination treatment of bladder cancer cells with TRAIL and cisplatin overcomes their resistance. The sensitization obtained with established cisplatin resistant and freshly isolated bladder cancer cells required low subtoxic concentrations of cisplatin, supporting the in vivo potential application of a combination of TRAIL and cisplatin for treating TRAIL resistant and cisplatin resistant bladder cancer.

[Renal cell carcinoma in the Birt-Hogg-Dubé syndrome: report of a case].

Birt-Hogg-Dubé (BHD) syndrome is a rare dermatological condition appearing with an autosomal dominant mode of inheritance. It was first reported in 1977 by Birt et al. and 28 cases have been reported since then. BHD syndrome is characterized by asymptomatic dome-shaped, skin-colored papules on the face and upper trunk. Recently, various neoplasms have been reported to associate with BHD syndrome, including three familial and one sporadic cases of renal tumors. We report another sporadic case with renal tumor. A 53-year-old woman complained of gross hematuria and visited our institute on November 1996. She visited the Department of Dermatology, Wakayama Medical College because of skin lesions on the face and upper trunk at her age of 44. These skin lesions were present since her mid twenties. Her daughter also had similar skin lesions and visited the same Department. There was no family history of renal tumor. The patient was diagnosed to have a right renal tumor, and radical nephrectomy was performed. Pathological diagnosis was renal cell carcinoma, papillary type. She underwent interferon injection therapy postoperatively, but died because of lung metastases on April 1997. This is the first reported case of renal tumor occurring in BHD syndrome in Japan.

p21(WAF-1/CIP-1), a downstream regulator of functional p53 loss, in transitional cell carcinoma of urothelium.

OBJECTIVES: The expression of p21(WAF-1/CIP-1), a downstream regulator of p53, is a universal cycline-dependent kinase inhibitor. The aim of this study is to determine whether p21 expression could be used as a prognostic marker in urothelial carcinomas. METHODS: By use of immunohistochemistry, we examined the expression of p21(WAF-1/CIP-1) in 60 patients with urothelial carcinomas and compared the results with the status of nuclear p53 and mdm2 accumulation, expression of type IV collagen in the basement membranes and upregulation of metalloproteinases (MMP-1, MMP-2, MMP-9). RESULTS: p21(WAF-1/CIP-1) immunoreactivity was observed in 51.7% of the tumors, and in only 39% of the tumors with functional p53 loss (nuclear accumulation of p53 and/or mdm2). p21(WAF-1/CIP-1) overexpression was not associated with grade and stage of the tumors and presence or absence of concomitant CIS. Moreover, p21(WAF-1/CIP-1) overexpression was not associated with upregulation of metalloproteinases or destruction of type IV collagen of basement membranes. CONCLUSIONS: Our results suggest that p21(WAF-1/CIP-1) expression is regulated by both p53-dependent and independent pathways and is not related to grade, stage or potential markers of invasion in urothelial carcinomas.

Complications of laparoscopic and retroperitoneoscopic adrenalectomies in 370 cases in Japan: a multi-institutional study.

A total of 370 laparoscopic adrenalectomies, including 311 transperitoneal (TP) and 59 retroperitoneal (RP) approaches, were performed in nine urologic centers, where the laparoscopic adrenalectomy was first begun independently in Japan, and their affiliated hospitals between January 1992 and September 1996. The clinical diagnoses of those 370 adrenal diseases were primary aldosteronism in 155 patients, Cushing's syndrome in 61. preclinical Cushing's syndrome in 21. pheochromocytoma in 16, nonfunctioning adenoma in 87, complicated cyst in ten, myelolipoma in nine, adrenal cancer in four and other diagnoses in eight (table 1). There was no mortality in this series. Intraoperative complication rate was 33/370 (9%) in total: 26/311(8%) in the TP procedures and 7/59 (12%) in the RP procedures (table 11). Postoperative complication rate was 24/370 (6%) in total: 22/311 (7%) in the TP procedures and 2/59 (3%) in the RP ones (table 111). Conversion rates to open surgery in total, in the TP and in the RP procedures were 13/370 (3.5%), 10/311 (3.2%) and 3/59 (5.1 %). respectively (table IV). Although the RP procedure has a lower morbidity rate compared to the TP procedure, more skill is required to overcome the drawback of the narrow working space and fewer anatomical landmarks.

Enhancement of Fas-mediated apoptosis in renal cell carcinoma cells by adriamycin.

Anti-Fas monoclonal antibody (mAb) kills Fas-expressing cells by apoptosis. Several anticancer agents also mediate apoptosis and may share common intracellular pathways leading to apoptosis with Fas. Thus, we reasoned that combination treatment of drug-resistant cells with anti-Fas mAb and drugs might overcome their resistance. We investigated whether anticancer agents enhance Fas-mediated apoptosis and cytotoxicity against renal cell carcinoma (RCC) cells. Treatment of ACHN RCC cells with anti-Fas mAb in combination with 5-fluorouracil, vinblastine, IFN-alpha, or IFN-gamma did not overcome resistance to these agents. However, combination treatment with anti-Fas mAb and Adriamycin (ADR) resulted in a synergistic cytotoxic effect. Furthermore, synergy was also obtained even when the exposure time was shortened from 24 h to 8 or 2 h. Synergy was also achieved in four other RCC cell lines and five freshly derived human RCC cells. Treatment with anti-Fas mAb in combination with epirubicin or pirarubicin also resulted in a synergistic cytotoxic effect on ACHN cells. Similar results were achieved with a combination of humanized anti-Fas mAb and ADR. Incubation of ACHN cells with ADR augmented the expression of Fas and p53, but not Bcl-2, Bax, or caspase-3. However, the activity of caspase-3 itself was apparently enhanced after treatment with ADR alone or combined treatment with anti-Fas mAb. The synergy obtained in cytotoxicity with anti-Fas mAb and ADR was also achieved in apoptosis. Exposure of ACHN cells and freshly derived RCC cells to ADR enhanced their susceptibility to lysis by peripheral blood lymphocytes and tumor-infiltrating lymphocytes. This study demonstrates that combination treatment of RCC cells with anti-Fas mAb and ADR might overcome their resistance. The sensitization required a low concentration of ADR and a short exposure time, thus supporting the potential in vivo application of a combination of ADR and anti-Fas mAb or immunotherapy in the treatment of ADR- and/or immunotherapy-resistant RCC.

Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men.

OBJECTIVE: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men. PATIENTS AND METHODS: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly. RESULTS: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13. CONCLUSIONS: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.

Urinary incontinence among community-dwelling people aged 40 years or older in Japan: prevalence, risk factors, knowledge and self-perception.

BACKGROUND: Urinary incontinence (UI) is a common problem in adults, especially among the elderly. We examined the prevalence and risk factors of UI and potential factors hindering individuals from seeking treatment for UI among a community-dwelling population aged over 40 years. METHODS: Data were collected by mailing a 23-item urinary incontinence questionnaire to a random sample of community-dwelling individuals aged 40-75 years (n=3500) in seven towns of Shiga Prefecture, Japan. Collected data were then used to estimate the prevalence of UI and to provide information regarding subtypes of UI, knowledge and self-perception about UI. RESULTS: The overall response rate was 52.5%. Prevalence of UI for male and female respondents were 10.5% and 53.7%, respectively. The incidence of urge incontinence increased as age increased in the male group. In women, stress incontinence was prevalent at all ages and the incidence of urge incontinence increased over 70 years of age. Urinary incontinence was more likely as activities of daily living limitations and cystitis increased. Women with a history of hysterectomy or diabetes mellitus and men who had stroke were at increased risk for UI. Of those who reported UI, only 3% had ever consulted doctors or other health care professionals concerning it, 25% recognized their condition as a disease and 38% considered it curable by appropriate treatments. In addition, 63% regarded UI as an unavoidable consequence of aging, 63% considered their condition was embarrassing and 54% were reluctant to seek treatment from a health professional. CONCLUSIONS: Although UI is common among community-dwelling individuals over 40 years of age, the majority of affected individuals remained untreated due to lack of knowledge and/or a negative perception of UI. Thus, community education on UI may be needed to increase the number of UI patients who receive treatment.

[A study on parameters to predict tumor volume for stage T1c prostate cancers of Gleason score 6 or less].

The number of cases of stage T1c prostate cancer has dramatically been increasing since the introduction of PSA as a screening test. The patients with T1c prostate cancer are usually treated by radical prostatectomy. In this group, however, some cancers are of small tumor volume and with a Gleason score of less than 7. These cancers are considered to be good candidates for watchful waiting management. We have investigated 40 patients with T1c prostate cancer treated by radical prostatectomy between 1996 and 1998. All 9 patients harboring tumors of Gleason score 7 or greater had tumors larger than 0.5 cm3. We have investigated PSA-related parameters including total PSA (PSA), PSA density (PSAD), free PSA, and % free PSA in 31 patients with T1c cancers of Gleason score 6 or less in order to clarify good preoperative predictors of tumor volume. We compared the distribution of PSA, PSAD, free PSA, and % PSA between the larger and smaller tumor groups. There was no significant difference in PSA, PSAD, or free PSA value. The small tumor group had a greater mean % free PSA than the larger tumor group (23.27 versus 11.88, p = 0.007). Areas under receiver operating characteristic curves were 0.715, 0.794, 0.636, and 0.842 for PSA, PSAD, free PSA and % free PSA. In stage T1c prostate cancer of Gleason score 6 or less, % free PSA may be the most useful preoperative predictor for tumor volume of 0.5 cm3 or greater.

[Long-term clinical results of 5 cases of urachal carcinoma].

Five cases of urachal carcinoma experienced in our hospital during the past 20 years are reported. Surgical resection is considered as the first treatment option of this disease, and other therapies to be less beneficial. Complete surgical extirpation and detection of recurrence in the early stage are considered to be important since local recurrence occurs frequently. We enforced the bladder preserving operation for 4 patients with urachal carcinoma except for 1 case with peritonitis carcinomatosa in the initial diagnosis, and multiple surgical treatment was performed again for 2 patients with recurrence. The bladder was preserved with no evidence of malignancy in three patients for 24, 19 and 5 years, respectively. In the initial management of urachal carcinoma, we believe that bladder-preserving surgery should be considered in selected cases though close follow-up is demanded. Herein, we also report the immunohistochemical study of paraffin-embedded specimens using anti-CEA, CA19-9, CA125 and p53 monoclonal antibodies. The positive reaction was observed in 100% (5/5) for CEA, 80% (4/5) for CA19-9, and 20% (1/5) for CA125. These results suggest that CEA may be a useful marker in the diagnosis of this neoplasm and early detection of its recurrence. Nuclear accumulation of p53 was observed in 80% (4/5), but it did not correlate with the disease progression.