Hepatolithiasis and intrahepatic cholangiocarcinoma: carcinogenesis based on molecular mechanisms

Hepatolithiasis is more frequently seen in East Asian countries than in Western countries, and it is well known to represent a high-risk state for intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcinoma is an aggressive tumor that shows a dismal outcome even after resection. Cancer results from multistep carcinogenesis; however, the precise molecular mechanisms involved in the genetic alterations in cancer remain unknown. The accumulation of alterations in cancer-related genes leads to disruptions in cell-cycle regulation and also to continuous cell proliferation. The present review provides an overview of cancer-related genes in intrahepatic cholangiocarcinogenesis arising in hepatolithiasis. Further study of molecular mechanisms in hepatolithiasis-related intrahepatic cholangiocarcinoma, and the delineation of the influence of the genes involved should lead to our understanding of cholangiocarcinogenesis.     

Results of the treatment of prostatic cancer

Two hundred and twenty patients with prostatic cancer were treated in our clinic during the past ten years between April, 1977 and March, 1987. The age distribution was from 45 to 91 years old and more than half of patients were in seventies. Stages A, B, C and D were 3.5%, 19.7%, 21.2% and 55.6%, respectively. Hormonal therapy was given in 175 cases (79.5%) as an initial treatment. The first therapy showed effectiveness in 181 (83.8%) of 216 cases; in 153 (87.4%) of 175 cases treated by hormonal therapy. Reactivation after the initial treatment was observed in 59 (32.6%) of 181 cases; in 48 (31.4%) of 153 cases treated by hormonal therapy. The interval between the start of treatment and reactivation for the stage D was significantly shorter than that for the other stages. Elevation of serum alkaline-phosphatase levels, accelerated erythrocyte sedimentation rate and hydronephrosis were significant risk factors for reactivation. Of the 220 cases, 51 (23.2%) died of advanced cancer. The overall 5-year survival rate was 41.2%. High grade and high stage were significantly related to the poor prognosis. In our studies, as hormonal therapy, maintenance on 100 mg of diethylstilbestrol diphosphate daily was found effective for the treatment of prostatic cancer.     

An immunohistochemical study of normal sweat glands using an antibody to the breast cyst fluid protein (GCDFP-15)

In this study, we applied the antibody against the molecular weight 15,000 protein purified from breast cyst fluid (GCDFP-15) to cutaneous tissue, especially to sweat glands. Breast cyst fluid was obtained by needle aspiration from patients with gross cystic disease. DEAE-cellulose column chromatography was performed and followed by SDS-polyacrylamide gel electrophoresis. Antisera against the purified protein were prepared in rabbits. We stained specimens of normal skin by the PAP method. The normal apocrine gland cells were strong positive and eccrine gland dark cells were positive. Eccrine gland clear cells were weak positive or negative. Duct cells of both glands were negative. From these observations, we suggest that this antibody is useful for detecting seromucous cells of sweat glands, including both the apocrine gland cells and eccrine dark cells in the skin.     

Primary localized cutaneous nodular amyloidosis: case report and biochemical analysis of amyloid.

We report a patient with scalp lesions of primary localized cutaneous nodular amyloidosis. The extensive examination revealed no systemic involvement. Analysis of glycosaminoglycans (GAGs) in amyloid deposits showed a twofold increase as compared with normal skin, which was due to the increase in dermatan sulfate. Local disorders of GAG metabolism may be related to the amyloid fibril formation. Amyloid fibrils were purified and identified electron-microscopically, which consisted of two major 12,000- and 13,000-dalton and minor 29,000- and 48,000-dalton peptides. Western blotting analysis showed a minor 29,000-dalton peptide reactive with antibodies against both kappa and lambda light chains of immunoglobulin. There is a possibility that some components of amyloid in some cases of primary localized cutaneous nodular amyloidosis may consist of both kappa and lambda immunoglobulin light chains.     

Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients

A reduced incidence of graft versus host disease (GvHD) has been documented among Japanese allogeneic bone marrow transplantation (BMT) patients, as the Japanese are genetically more homogeneous than western populations. To clarify whether this ethnic difference affects the results of allogeneic peripheral blood stem cell transplantation (PBSCT), we conducted a nationwide survey to compare clinical outcomes of allogeneic PBSCT (n = 214) and BMT (n = 295) from a human leucocyte antigen-identical-related donor in Japanese patients. The cumulative incidence of grades II-IV acute GvHD was 37.4% for PBSCT and 32.0% for BMT. The cumulative incidence of extensive chronic GvHD at 1 year was significantly higher after PBSCT than BMT (42% vs. 27%; P < 0.01). The organ involvement patterns of GvHD were different between the two groups. By multivariate analyses, the incidence of chronic GvHD was significantly increased in PBSCT, whereas the stem cell source did not affect the incidence of acute GvHD, transplant-related mortality, relapse or survival. We concluded that Japanese PBSCT patients have an increased risk of chronic GvHD compared with BMT patients, but the incidence of acute GvHD was still lower than in western populations. Thus, the choice of haematopoietic stem cell source should be considered based on data for individual ethnic populations.     

Suppression of body weight gain preserves acute insulin response to glucose in the portal vein of spontaneously type 2 diabetic rats with visceral obesity

The age-related changes in acute insulin response after glucose loading and the influence of suppression of body weight gain were investigated by using blood samples from portal and peripheral veins. We placed indwelling catheters in the portal vein of 12- and 24- wk-old Otsuka Long-Evans Tokushima fatty (OLETF) rats (n = 8, 12), and age-matched control Long-Evans Tokushima Otsuka (LETO) rats (n = 8, 6). To suppress the body weight gain, 6 out of 12 OLETF rats were fed chow containing 50 ppm voglibose (VOG) from 8 until 24 wk of age. After fasting for 17 h, rats underwent 1 g/kg oral glucose tolerance test (OGTT). Peripheral glucose levels after glucose loading were significantly higher in 12- and 24-wk-old OLETF rats than in the age-matched LETO rats. Values for delta insulin 15 min/delta glucose 15 min (delta I15 min/delta G15 min) in portal blood were 0.029 +/- 0.011 and 0.009 +/- 0.009 (12 wk of age) and 0.03 +/- 0.03 and -0.01 +/- 0.01 (24 wk of age) in the LETO rats and OLETF rats. At the age of 24 wk, the body weights in VOG-treated OLETF rats were significantly lower than those in the OLETF rats. And there was significantly greater acute insulin response to glucose in VOG-treated OLETF rats than in the OLETF rats. Acute insulin response to glucose decreased with advancing age and the suppression of body weight gain preserved the response in spontaneously type 2 diabetic rats with visceral fat obesity.     

A trial of infection control measure by clinical microbiology laboratory

In 1998, we developed a Total Infection Control System in Saga Medical School Hospital, and would like to introduce it for the practical use. This system was named "Dr. FLEMING" (Flexible Microbiological Test & Information System for the New Generation) and is expected to help physicians by providing highly valuable test results and useful information. For example, bacterial identification and drug susceptibility test can be completed within 4-6 hrs after bacterial colony is isolated, and the test report the contains full-colored pictures to enhance understanding. In addition, we have made an information center for infectious disease, where physicians can have access to various data bases outside our hospital. Furthermore, we offer many kinds of useful information to physicians working at other medical facilities to assist their clinical practice of infectious diseases.