Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia, 1984-1999.

We report the long-term results of Tokyo Children's Cancer Study Group's studies L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic leukemia, which were conducted between 1984 and 1999. The value of event-free survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not improved in the following two studies, and eventually improved to 75.0+/-1.8% at 10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of induction failure because of infection and delayed remission in very high-risk patients. The L92-13 study was characterized by short maintenance therapy; it resulted in poor EFS, particularly in the standard-risk (SR) group and boys. Females did significantly better than males in EFS in the early three studies. The gender difference was not significant in overall survival, partly because >60% of the males survived after the testicular relapse. Randomized studies in the former three protocols revealed that intermediate- or high-dose methotrexate therapy significantly reduced the testicular relapse rate. In the L95-14 study, gender difference disappeared in EFS. Contrary to the results of larger-scale studies, the randomized control study in the L95-14 reconfirmed with updated data that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to 100, 80, 44, and 44% of the patients in the studies, respectively. Isolated central nervous system relapse rates decreased to <2% in the last two trials. Secondary brain tumors developed in 12 patients at 8-22 years after cranial irradiation. Improvement of the remission induction rates and the complete omission of irradiation are currently main objectives in our studies.

Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma.

AIM: The aim of this study is to assess the poly ADP-ribosylation activity in human hepatocellular carcinoma (HCC) and in liver cirrhosis (LC) as compared to the activity in normal livers (NL). METHODS: Hepatocellular carcinoma and LC tissues were sampled from 19 patients with HCC. Normal liver tissue was obtained from 19 patients with metastatic liver cancer. Poly ADP-ribosylation activity of these tissues was measured by using [32P]-adenylate nicotinamide adenine dinucleotide (NAD)-incorporation into the 116-kDa protein. Nicotinamide adenine dinucleotide glycohydrolase activity of these tissues was determined with thin layer chromatography. The immunohistochemical expression of Ki-67 was also assessed as a parameter of cell proliferative activity. RESULTS: The poly ADP-ribosylation of the 116 kDa protein was significantly increased in patients with HCC and LC as compared with NL (P<0.0001, P<0.05, respectively) and was inhibited by poly (ADP-ribose) polymerase inhibitors in a dose-dependent manner. There was no significant difference in NAD glycohydrolase activity among the three groups. A significant correlation was found between the Ki-67 positive cell rate and the relative radioactivity of poly ADP-ribosylation in HCC patients (r=0.794, P<0.0001). The poly ADP-ribosylation of the 116 kDa protein of LC was significantly higher in patients who had recurrences of HCC after hepatic resection than in patients without recurrence (P<0.05). CONCLUSION: Poly ADP-ribosylation of the 116 kDa protein in HCC patients might be enhanced with its proliferative activity, and poly ADP-ribosylation of the same protein in LC patients might be a useful parameter of carcinogenic potential for predicting HCC recurrence after hepatectomy in patients who have had HCC.

Hepatic resection of liver metastases from gastric carcinoma.

OBJECTIVES: Previous reports have indicated that results of the surgical resection of hepatic metastases from gastric carcinoma have been unsatisfactory. We therefore evaluated the results of aggressive surgical resection for hepatic metastases from gastric carcinoma, to identify candidates with a better likelihood of survival. METHODS AND RESULTS: Twenty-one patients with synchronous or metachronous hepatic metastases from gastric carcinoma underwent hepatic resections. Five patients were still alive, without recurrence, at 10, 41, 46, 117, and 176 months after their hepatic resection. Sixteen patients died of recurrence 5-33 months (mean, 10 months) after hepatic resection. A significant difference in the number of node metastases (solitary or multiple) and in the tumor-free margin of the resection (< 10 mm or > 10 mm) was found between survivors and those who died. CONCLUSION: Hepatic resection for hepatic metastases from gastric carcinoma may improve the prognosis in patients with a solitary metastasis if adequate tumor-free margins (> 10 mm) can be obtained.

A successful treatment for hepatocellular carcinoma with atrial tumor thrombus.

A 66-year-old man with an advanced hepatocellular carcinoma and tumor thrombus extending into the right atrium was treated by transcatheter arterial infusion of lipiodol and aclarubicin. This brought about a remarkable reduction of the tumor and the disappearance of the right atrial tumor thrombus. The tumor was then radically resected by hepatic posterior segmentectomy with combined resection of the right hepatic vein, where the tumor thrombus remained. He is doing well without any signs of recurrence 22 months after the operation.

Reduced hepatic functional reserve in cirrhosis and obstructive jaundice with special reference to histological morphometric analysis and galactose elimination capacity.

To evaluate liver dysfunction in patients with obstructive jaundice (OJ), morphological and functional hepatic mass was analyzed in comparison with cirrhosis (LC). Total hepatic parenchymal ratio (THPR) was estimated by morphometric analysis and hepatic functional mass by galactose tolerance test (GaTT) in 30 patients who underwent hepatectomy. The value of GaTT in patients with LC was remarkably depressed compared to those with normal liver function (p < 0.001). It was also depressed in OJ (p < 0.05 vs. normal liver), but less than in LC (p < 0.05). However, THPR decreased only in LC (p < 0.05 vs. either normal liver or OJ). A significant correlation between the value of GaTT and THPR was revealed in patients with LC, but not in OJ. These results suggested that liver dysfunction in OJ was independent of the decreased number of hepatocytes, differing from LC.

Guide to the clinical assessment of on-eye wettability of rigid gas permeable lenses.

The number of rigid gas permeable (RGP) contact lens materials is increasing rapidly. One of the most critical issues for acceptance of new materials is lens wettability. This paper describes techniques for assessing lens wetting characteristics while the lenses are worn on the eye, and relates each observation to the lens material properties or patient tear characteristics. This method of lens wetting assessment is intended to aid the practitioner in determining the optimal lens material for a patient, based upon assessment of the interactions inherent in the lens-eye system.