Malignant fibrous histiocytoma of the lung

Primary malignant fibrous histiocytoma (MFH) of the lung is very rare. To date, only 32 reports of 63 cases of primary MFH of the lung have appeared in English, excluding tumors arising from the pulmonary arteries and pleura. We describe a patient with primary MFH of the lung who developed brain metastasis and involvement of pulmonary great vessels. In addition, we reviewed previously reported cases to establish the clinical characteristics and most appropriate management of primary pulmonary MFH. When disease is sufficiently limited, complete resection remains the mainstay of treatment.     

A case of distant metastasis from advanced gastric cancer treated with TS-1, which maintained NC (no change) for 9 months

A 57-year-old woman was admitted to our hospital for advanced gastric cancer located in the gastric antrum. Abdominal CT scan revealed multiple liver metastases and lymph node metastasis along the abdominal aorta which was diagnosed as stage IV gastric cancer. The patient received daily oral administration of 75 mg TS-1, a novel oral anticancer agent. Each treatment course consisted of a four-week administration followed by two drug-free weeks. No change (NC) was observed in the liver metastasis on the abdominal CT scan after TS-1 administration, but lymph node swelling along the abdominal aorta decreased (PR). Grade 2 depilation was observed as the only adverse effect. The patient had a performance status of 1 or 2, and kept a fair QOL. TS-1 is an excellent new anticancer agent and, we have high expectations for its use in combined therapy with other drugs.     

A new prognostic scoring system involving des-gamma-carboxy prothrombin as a useful marker for predicting prognosis in patients with hepatocellular carcinoma

A staging system for hepatocellular carcinoma was reported from Italy (CLIP). In this study, we evaluate the CLIP scoring system and establish a new scoring system for predicting the prognosis of patients with hepatocellular carcinoma. Patients (n=141) who were diagnosed and who underwent initial treatment at our single institution were recruited retrospectively into this study. We evaluated markers for prognosis, using a stratified Cox proportional hazard regression model and Kaplan-Meier survival analysis. CLIP score differentiated patients with different survival experiences by Kaplan-Meier estimated survival analysis. However, with respect the CLIP score, more than two thirds of patients were included in the early stage (CLIP 0-1), and the group with better prognosis than the survival rate of all patients was the only one with CLIP 0. Multivariate analysis revealed that des-gamma-carboxy prothrombin (DCP) >/=100 mAU/ml (relative risk, 2.06; P=0.0218) was statistically significant as a predictor of poor survival. A new prognostic scoring system included DCP classified patients to 6 well-balanced groups (score 0-5). The new prognostic scoring system 0 group (14.9% of the cohort) and the CLIP score 0 group (34.0% of the cohort) had a median survival of 66.9 and 61.6 months. The new prognostic scoring system performs better for prediction of survival than either the CLIP score or the Child-Pugh stage. In conclusion, the described scoring system provides more accurate prognostic information than the CLIP scoring system. It may help physicians decide more appropriate clinical and therapeutic management.     

Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl)nitrosamine in rats after initiation

Previously we reported that benzyl isothiocyanate (BITC) strongly enhanced rat urinary bladder carcinogenesis after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), while potently inhibiting BBN-induction of lesions when given simultaneously with the carcinogen. In the present experiment, the effects of simultaneous treatment with BITC and low-dose BBN on the postinitiation period of rat urinary bladder carcinogenesis were examined. After treatment with 500 ppm BBN for 4 weeks for initiation, groups of 20, 6-week-old, F344 male rats were given 25 ppm BBN alone, basal diet alone, or 100 or 1000 ppm BITC in the diet together with or without 25 ppm BBN in their drinking water for 36 weeks and then killed for autopsy. Further groups consisting of 10 rats each were similarly given BITC or the basal diet together with or without 25 ppm BBN, without initiation treatment. In the initiated groups receiving subsequent BBN exposure, papillary and nodular hyperplasia, dysplasia and carcinoma incidences were significantly increased, and they were further increased by the combined treatment with 100 and 1000 ppm BITC in a dosedependent manner. In the non-initiation groups, carcinomas were only observed in a single rat in each of the BBN-treated control and BBN/BITC 100 ppm treatment groups. The results indicate that simultaneous treatment with BITC and a low dose of BBN does not inhibit, but rather enhances rat urinary bladder carcinogenesis after appropriate initiation, and further suggest that BITC may be a human risk factor, at least in high-risk populations.     

Neostigmine and polyethylene glycol electrolyte solution for the therapy of acute hepatic encephalopathy with liver cirrhosis and ascites

We treated a 75-year-old man who had non-B and non-C, and Child's class C liver cirrhosis and acute hepatic encephalopathy with neostigmine and polyethylene glycol electrolyte solution. He received repeated transcatheter artrial embolization and percutaneous ethanol injection combination therapy for multiple hepatocellular carcinomas, which controlled his disease for 25 months from the first treatment. He was admitted in a state of hepatic coma after being found unresponsive at his home. With the consent of the patient's family, we gave him 1.0 mg of neostigmine intramuscularly to improve his peristaltic movement, and 2 L of polyethylene glycol electrolyte solution through a nasogastric tube for 4 hours to reduce the production and absorption of gut-derived toxins of nitrogenous compounds. Using these treatments, the blood ammonia level decreased to the normal range within 8 hours, and the coma disappeared after 2 days. We suggest that a combination approach of neostigmime and polyethylene glycol electrolyte solution may be one of the most effective treatments for acute hepatic encephalopathy associated with liver cirrhosis and ascites.     

Improvement of cerebral blood flow by olprinone, a phosphodiesterase-3 inhibitor, in mild heart failure

Cerebral blood flow (CBF) is reduced in heart failure (HF). For the treatment of acute HF, a phosphodiesterase-3 inhibitor, olprinone (OL), yields an increase in myocardial contractility and a decrease in arterial afterload. During a 15-min intravenous infusion of OL (0.2 microg/kg/min), regional CBF at 6 sites of each cerebral cortex was examined using technetium-99m-ethylcysteinate dimer brain SPECT in 18 HF patients and 7 age-matched normal subjects. The baseline CBF was significantly reduced in HF (43.0 +/- 3.9 ml/min/100 g) compared to that in normal subjects (48.0 +/- 4.6 ml/min/100 g, p < 0.01). The baseline CBF showed a significant negative correlation with the increase in CBF during the OL infusion in HF (r = -0.38, p < 0.01) and normal subjects (r = -0.65, p < 0.01). The percent increase in CBF was significantly greater in HF (13.7%) than in normal subjects (9.8%, p < 0.046). In patients with HF, the CBF of the cerebral cortex was decreased, but was increased by OL infusion.     

Excess dietary histidine decreases the liver copper level and serum alanine aminotransferase activity in Long-Evans Cinnamon rats

Long-Evans Cinnamon (LEC) rats spontaneously develop fulminant hepatitis, associated with excess Cu accumulation in the liver: thus, they are considered an animal model of Wilson's disease. In the present study, we investigated the ability of excess dietary histidine to reduce the excess accumulation of liver Cu in LEC rats by comparing them with Fischer rats. The results clearly showed that the excess-histidine diet markedly stimulated the Cu excretion in urine, and significantly decreased the liver Cu content in LEC rats by 47.5%. The serum Cu content in LEC rats was not influenced by excess dietary histidine. We also compared the effects of excess dietary histidine on some liver antioxidant enzyme activities, liver and serum lipid levels and serum alanine aminotransferase activity of LEC and Fischer rats. Dietary histidine decreased the activities of total and Cu,Zn-superoxide dismutase in the liver of both strains. In LEC rats, the liver cholesterol content decreased, and serum cholesterol and phospholipids levels increased on feeding the excess-histidine diet. When fed on the basal diet, the serum alanine aminotransferase activity was higher in LEC rats than in Fischer rats, but a significant decrease in serum alanine aminotransferase activity of LEC rats was observed on feeding the excess-histidine diet. These results suggest that excess dietary histidine is effective in removing Cu ions from the liver of LEC rats. Thus, it may be of benefit in the prevention or treatment of liver injury in LEC rats and in patients with Wilson's disease.     

Lack of correlation between mitotic arrest or apoptosis and antitumor effect of docetaxel

Purpose: To determine, as we did for paclitaxel, whether mitotic arrest and apoptosis induced in murine tumors in vivo by docetaxel correlate with the drug's antitumor effect and whether the antitumor efficacy of docetaxel depends on p53 mutational status of tumors. Methods: C3Hf/Kam mice were implanted with one of the following 15 syngeneic tumors: seven adenocarcinomas (MCa-4, MCa-29, MCa-35, MCa-K, OCa-I, ACa-SG, and HCa-I), two squamous cell carcinomas (SCC-IV and SCC-VII), five sarcomas (FSa, FSa-II, Sa-NH, NFSa, and Sa-4020) and one lymphoma (Ly-TH). When the tumors had grown to 8 mm in diameter, the mice were treated with 31.3 mg/kg docetaxel i.v. Tumor growth delay was the endpoint of docetaxel's antitumor effect. In separate groups of mice, mitotic arrest and apoptosis were determined micromorphometrically 1 to 72 h after docetaxel treatment. Tumors were assayed for their p53 status by sequence analysis of RNA prepared from freshly excised tumors. Results: Docetaxel caused statistically significant growth delay in six of seven adenocarcinomas, three of five sarcomas, and the lymphoma, but not in either of the squamous cell carcinomas. The drug induced mitotic arrest in all tumor types, but to various degrees ranging from 6.4 +/− 0.4% to 25.1 +/− 0.1%. In contrast, docetaxel induced appreciable apoptosis in only 5 of 15 tumors, with 10.3 +/− 1.6% being the highest apoptotic value. Neither mitotic arrest nor apoptosis were significantly correlated with tumor growth delay. However, tumors that responded to docetaxel by significant tumor growth delay histologically displayed massive cell destruction by cell lysis, and four of these tumors also showed marked infiltration with mononuclear lymphoid cells. Of the 15 tumors only 3 had mutant p53. Conclusions: Docetaxel exhibited a strong antitumor effect in two-thirds of murine tumors, and on a milligram per kilogram basis was more effective than paclitaxel against the same tumors. The drug was a potent inducer of mitotic arrest but a weak inducer of apoptosis, neither of which correlated with its antitumor effect. Tumor cell lysis appeared to be a major mode of tumor cell destruction and can be regarded as the main mechanism underlying antitumor efficacy of docetaxel. In contrast, paclitaxel's antitumor efficacy is related to its ability to induce apoptosis. At the molecular level, there was no dependency of antitumor efficacy of docetaxel on p53 mutational status of tumors. Received: 3 March 1998 / Accepted: 14 May 1998     

Clinicopathological features of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide and its incidence is increasing concomitantly with the increase in the prevalence of metabolic syndrome. Fatty liver encompasses a broad pathological spectrum of disease, from relatively benign accumulation of fat (simple steatosis) to progressive non-alcoholic steatohepatitis (NASH), which is associated with necroinflammation and fibrosis. Approximately 20-30% of the Japanese population is estimated to have NAFLD, 10% of which is suggested to have NASH. The most worrisome feature of NASH is the potential progression to cirrhosis, hepatocellular carcinoma (HCC), and finally, mortality. Several factors, such as insulin resistance, adipokines, endotoxins and oxidative stress, are involved in the pathogenesis of NASH. However, the precise etiological mechanism of NAFLD/NASH has yet to be elucidated. This article reviews the clinical background, pathogenesis, new diagnostic approaches and future directions regarding NAFLD/NASH.     

The effects of antifungal stewardship programs at a tertiary-care teaching hospital in Japan

Patients with invasive fungal diseases (IFDs) generally have a high mortality rate, and resistance to antifungal drugs and the high costs associated with it have led to recent problems, necessitating the appropriate use of antifungals. To this end, we launched Antifungal Stewardship Programs (AFSPs) in our hospital. Patients who were systemically administered antifungals from January 2011 to December 2016 were enrolled this study and divided into pre-intervention and intervention groups. No significant difference was observed in defined daily doses per 1000 patient-days (23.3 ± 8.0 vs 20.4 ± 10.8, p = 0.251) between the groups. The monthly average for the days of therapy per 1000 patient-days was significantly lower in the intervention group (15.1 ± 3.1 vs 12.7 ± 4.3, p = 0.009). The cost of the antifungals reduced over the 3-year period by $260,520 (13.5%). Furthermore, a decreasing trend was observed in both the 30-day mortality (40.9% vs 30.0%, p = 0.414) and in-hospital mortality (63.6% vs 36.7%, p = 0.054) in patients with candidemia. Our results indicate that AFSPs are efficacious and cost-effective approaches.