Yoshihiro Hasui

Significance of invasion to the muscularis mucosae on the progression of superficial bladder cancer

OBJECTIVE We tried to determine the significance of invasion to the muscularis mucosae on the progression of superficial bladder cancer. METHODS We subclassified superficial bladder cancer showing lamina propria invasion into two groups: with (pT1b) or without cancer invasion to or near the muscularis mucosae (pT1a). RESULTS Of 164 bladder cancers, 76 showed no lamina propria invasion and 88 did. In the tumors with lamina propria invasion, 60 were diagnosed as pT1a and 28 as pT1b. The progression rate of pT1b cancer (53.5%) was significantly higher than that of pT1a cancer (6.7%) (P < 0.01). Regardless of size, number, or grade of tumor, the progression rate of pT1b cancer was significantly higher than that of pT1a cancer (P < 0.01). CONCLUSIONS We stress that patients with superficial cancer invading to or near the muscularis mucosae should be followed up carefully after transurethral resection.

Clinical relevance of hepsin and hepatocyte growth factor activator inhibitor type 2 expression in renal cell carcinoma

Cell surface proteolysis is important for the generation of bioactive proteins mediating tumor progression. Recent studies suggest that the membrane‐anchored cell surface proteinases matriptase and hepsin have significant roles in tumors. We analyzed the expression and clinical relevance of matriptase and hepsin, and their inhibitors hepatocyte growth factor activator inhibitor type 1 (HAI‐1) and type 2 (HAI‐2) in 66 cases of conventional renal cell carcinomas (RCC). The mRNA level was evaluated in paired samples from tumor and non‐tumorous renal tissues by real‐time reverse transcription–polymerase chain reaction. As matriptase and hepsin potently activate the proform of hepatocyte growth factor (HGF), the expression of HGF and its receptor, c‐Met, was also analyzed. Although upregulation of matriptase was observed occasionally in RCC, the expression level was not associated with prognostic parameters. Hepsin was downregulated in RCC, particularly in early stage disease, but upregulated in advanced stages. There was a trend of higher hepsin expression in RCC with distant metastasis, and Kaplan–Meier survival curves showed that high hepsin expression was associated with reduced overall survival (P < 0.01, log‐rank test). Moreover, multivariate analysis indicated that hepsin was an independent prognostic factor. Overexpression of HGF or c‐Met also showed reduced overall survival. We also observed a tendency of low HAI‐2 expression with reduced overall survival and a statistical association between high hepsin and low HAI‐2 level. No associations were observed between matriptase and HAI‐1 and HAI‐2. Our findings suggest that the balance between hepsin and its inhibitor, HAI‐2, may have prognostic value in RCC. (Cancer Sci 2007; 98: 491–498)

Retroperitoneal bronchogenic cyst: Report of a case and literature review

A large cystic mass was found in the subdiaphragmatic region of a 46‐year‐old woman who had complained of continuous pain in the left flank . The cyst was located in the retroperitoneum just below the diaphragm and was adhered to the diaphragmatic skeletal muscle and abdominal aorta, but was separate from the spleen, pancreas, left adrenal gland and left kidney. The surgically resected cyst measured 8 × 8 × 7 cm and was filled with protein‐rich fluid, which contained amylase and embryonal proteins such as carcinoembryonic antigen, CA125 and CA19‐9. Histologically, the cyst wall was composed of a fibrovascular connective tissue containing thin smooth muscle layers and mucus‐secreting glands and was lined by a ciliated pseudostratified or tall columnar epithelium without dysplastic changes. Thus, a diagnosis of bronchogenic cyst, which is usually discovered in the posterior part of the mediastinum, was made. A rare case of bronchogenic cyst and a literature review is presented.

The Content of Urokinase-Type Plasminogen Activator and Tumor Recurrence in Superficial Bladder Cancer

The contents of urokinase-type plasminogen activator were estimated in superficial bladder cancer from 42 patients undergoing transurethral resection for the first time. Tumor recurred in 11 of 16 patients (68.8%) with high urokinase-type plasminogen activator content (8 ng. urokinase-type plasminogen activator per mg. protein and more) and in 12 of 26 (46.2%) with low urokinase-type plasminogen activator content. In the high content group 8 patients (50%) had disease progression compared to 2 (7.7%) in the low content group (p < 0.01). The progression rates in the high urokinase-type plasminogen activator group with stage pTa disease or tumors more than 1 cm. large were significantly higher than those in the low urokinase-type plasminogen activator group (p < 0.05). The recurrence and progression rates in the high content group with stage pT1, grades 2 and 3, single and multiple tumors, and tumors less than 1 cm. large were higher than those in the low content group. The progression-free survival rate in the high content group was significantly lower than that in the low content group (p < 0.005). In conclusion, urokinase-type plasminogen activator content may be a useful marker to predict recurrence and progression of superficial bladder cancer.

Prognostic value of urokinase-type plasminogen activator in patients with superficial bladder cancer

OBJECTIVES A number of studies have demonstrated that urokinase-type plasminogen activator (u-PA) is one of the major enzymes in the development of cancer invasion and metastasis. We examined the possibility that u-PA content is an independent prognostic marker for superficial bladder cancer. METHODS The u-PA content was estimated in superficial bladder cancer from 52 patients undergoing transurethral resection for the first time. The survival rates of the patients were calculated and the prognostic values for u-PA content (less than 8 ng/mg protein versus more than 8 ng/mg), Stage (pTa or pT1), grade (1 and 2 versus 3), number (single versus multiple), and size (less than 1 cm versus more than 1 cm) of tumor were determined by a multivariate regression model. RESULTS Development of cancer invasion and metastasis was observed in 3 and 8 patients, respectively. The survival rate of the patients with high u-PA content was significantly lower than those with low u-PA content (P < 0.005). In the multivariate regression analysis, u-PA content was the most important risk factor for the prognosis, compared with the other factors: tumor stage, grade, multiplicity, and size. CONCLUSIONS We have first shown that u-PA content is a new independent prognostic marker in patients with superficial bladder cancer.

The Prognostic Significance of Vascular Invasion in Upper Urinary Tract Transitional Cell Carcinoma

The prognostic significance of vascular invasion was evaluated in a retrospective series of 30 patients with upper urinary tract cancer who underwent a potentially curative operation. Vascular invasion was found in 11 patients (36.7%). The incidence of vascular invasion was well correlated with tumor grade and stage. The incidence of metastases postoperatively was significantly higher in the patients with (72.7%) than without (21.1%) vascular invasion (p < 0.01). The survival rate of the patients with vascular invasion was significantly lower than in those without vascular invasion (p < 0.005). In multivariate Cox regression analysis the prognostic value of vascular invasion was independent of tumor stage and grade. These results indicate that vascular invasion should predict a more unfavorable outcome in patients with upper urinary tract cancer as an independent morphological indicator.

Bladder Function in Elderly Men with Subclinical Brain Magnetic Resonance Imaging Lesions

Among 43 men more than 60 years old who complained of urinary irritative symptoms 40 had subclinical lesions in the brain on magnetic resonance imaging (MRI). Of these 40 patients 23 (57.5%) had detrusor hyperreflexia. The mean age of the patients with and without detrusor hyperreflexia was 75.8 and 68.2 years, respectively, which is a statistically significant difference. Patients with detrusor hyperreflexia were more likely to have lesions of the basal ganglia than patients without detrusor hyperreflexia. This study suggests that detrusor hyperreflexia, subclinical MRI lesions in the brain and aging are intimately interrelated.

Effects of suramin on metastatic ability, proliferation, and production of urokinase-type plasminogen activator and plasminogen activator inhibitor type 2 in human renal cell carcinoma cell line SN12C-PM6

Effects of suramin, a polysulfonated naphthylurea compound, on metastatic ability, proliferation, and production of plasminogen activators and plasminogen activator inhibitors were studied using the highly metastatic human renal cell carcinoma cell line, SN12C-PM6. After renal subscapular implantation of tumor cells in nude mice, suramin significantly inhibited metastasis of tumor cells to the lungs and liver. In vitro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 µg/ml). Plasminogen activator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 µg/ml), whereas urokinase-type plasminogen activator (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be beneficial for the treatment of patients with an early stage of renal cancer with potential risk of metastasis.

47,XXY/48,XXY,+21 Chromosomal Mosaicism Presenting as Hypospadias with Scrotal Transposition

The syndrome of 47,XXY/48,XXY,+21 chromosomal mosaicism, double aneuploidy, is extremely rare and characterized by combined manifestations of Klinefelters and Downs syndromes. We report a case of XXY/XXY,+21 mosaicism presenting with hypospadias associated with scrotal transposition.

Primary Adenocarcinoma Arising from a Paraurethral Cyst in a Female Patient

A very rare case of primary adenocarcinoma arising from a paraurethral cyst in a 63-year-old woman is reported. Initially she was diagnosed as having a simple paraurethral cyst because of absent communication with the urethra. The resected paraurethral cyst was histologically associated with adenocarcinoma. We also performed chemotherapy composed of methotrexate, vinblastine, Adriamycin and cisplatin because of lymph node metastasis. Our treatment, however, was not effective and the patient died of systemic metastases.