Thorotrast-Induced Multiple Primary Malignant Tumors of the Liver--Cholangiocarcinoma and Malignant Hemangioendothelioma

A case of multiple primary malignant tumors of the liver (cholangiocarci-nomaand malignant hemangioendothelioma) that developed 40 yearsafter Thorotrast administration is described, with radiologicaland autoradiographic findings. The estimated organ dose to theliver was approximately 580 rads.     

Hepatocyte growth factor: Molecular structure and implications for a central role in liver regeneration

Hepatocyte growth factor (HGF) is a most potent factor for mature parenchymal hepatocytes in primary culture and may act as a trigger for liver regeneration. We purified HGF from rat platelets to homogeneity and cloned both human and rat HGF cDNA. HGF is a heterodimer molecule composed of the 69 kDa alpha-subunit and the 34 kDa beta-subunit. HGF has no amino acid sequence homology with other known peptide growth factors and possesses the highest potential among known growth factors to stimulate proliferation of hepatocytes in primary culture. HGF is derived from a single chain precursor of 728 amino acid residues and the precursor is proteolytically processed to form a two-chain mature HGF. The alpha-subunit of HGF contains 4 kringle structures and HGF has a homology (38%) with plasmin. Biologically active recombinant human HGF could be expressed from COS-1 cells and CHO cells transfected with cloned cDNA. HGF activity and the HGF mRNA level are markedly increased in the liver following insult such as hepatitis, by the administration of hepatotoxins, ischaemia, physical damage and partial hepatectomy. Moreover, HGF mRNA is induced in the lung and kidney, in the presence of liver injury. In situ hybridization revealed that HGF-producing cells in liver are non-parenchymal liver cells, presumably Kupffer and sinusoidal endothelial cells. Therefore, HGF from neighbouring cells (Kupffer and sinsuoidal endothelial cells) and distal organs (lung and kidney) may function as a trigger for liver regeneration by both a paracrine mechanism and an endocrine mechanism. HGF has mitogenic activity for renal tubular epithelial cells, epidermal melanocytes and keratinocytes as well as mature hepatocytes, and has the potential to promote cell migration for some epithelial cells, including normal human keratinocytes. Since cell growth and cell motility are relevant to tissue repair and embryogenesis, HGF may well have important roles in tissue repair and embryogenesis as well as in liver regeneration.     

Controlled Study of Therapeutic Granulocyte Transfusions in Granulocytopenic Patients with Severe Infections

The effectiveness of therapeutic granulocyte transfusions wasstudied in a controlled trial involving 75 granulocytopenicpatients with severe infections. Patients who had granulocytecounts of less than 200/mm³ and no response to antibiotic therapywere assigned to receive antibiotic therapy alone or granulocytetransfusions plus antibiotic therapy. Granulocytes were collectedby filtration leukapheresis (FL), intermittent flow centrifugeleukapheresis (IFCL) or continuous flow centrifuge leukapheresis(CFCL). Therapeutic effects of granulocyte transfusions wereevaluated on the basis of 20-day survival after entry into thestudy. The patients were divided into three groups: 1) 22 patientsreceived antibiotic therapy alone for 29 infectious episodes(control group); 2) 27 patients received 131 transfusions ofgranulocytes collected by FL for 31 infectious episodes (FLgroup); 3) 26 patients received 139 transfusions of granulocytescollected by IFCL and CFCL for 27 infectious episodes (IFCL& CFCL group). The overall survival of the transfused patientswas not significantly different from that of the untransfusedpatients. Similarly, there was no significant difference insurvival between the transfused and untransfused patients whenthe data concerning septicemia were analyzed. When patientsshowed bone-marrow recovery, which was indicated by recoveryof granulocytes to 500/mm³ or more during the study, 20-daysurvival was observed in 13 of 14 untransfused patients andin all of 26 transfused patients. In contrast, the survivalrate for the patients without bone-marrow recovery was 13% (2/15)in the control group, 39% (7/18) in the FL group and 57% (8/14)in the IFCL & CFCL group respectively. Thus, the survivalrate was significantly higher for the transfused than for theuntransfused patients. These observations suggest that therapeutic granulocyte transfusionsmay be of limited value in improving the outcome of severe infectionsin persistently granulocytopenic patients. Since bone-marrowrecovery is a critical factor for the prognosis of severe infections,therapeutic granulocyte transfusions do not provide any beneficialeffects in granulocytopenic patients whose bone-marrow functionwill recover.     

Familial occurrence of idiopathic portal hypertension: Observations in two sisters

Abstract Idiopathic (non-cirrhotic) portal hypertension is one of the major problems in developing countries, but the aetiology is not known. Two sisters with idiopathic portal hypertension diagnosed by percutaneous transhepatic catheterization of the portal vein and liver biopsy are reported. Both patients had large spontaneous portal-systemic shunts. This seems to be the first report of a familial aggregation of this disorder.     

Tobacco use among Japanese schoolchildren: results from preliminary study of Japan adolescent smoking survey (JASS)

Over the past two decades many studies have shown associationsbetween smoking and increased health problems. Smoking amongchildren is especially a major public health concern. Preventingyoung people from developing a smoking habit is an importantgoal for school health education. In Japan, it is difficult to collect accurate data regardingadolescent smoking behaviour, because in Japan smoking underthe age of 20 is prohibited by law. Therefore, a large surveyof smoking habits of young Japanese people was overdue. Numeroussurveys have been carried out since the late 1970s, but thesehave been limited in sample size or geographic area. The Japan Adolescent Smoking Survey (JASS) is probably the largestnumerical survey of smoking behaviour and opinions of schoolchildrenever carried out in Japan. Here the authors show the preliminaryresults of JASS. The goals of the JASS study are to standardize the method ofmeasurement in the smoking behaviour of young children. We believeit is now possible to compare national and international smokingrates of young people, and further, to develop and evaluateteaching methods about smoking for schoolchildren on the basisof this standardization. This report presents the tobacco use among schoolchildren inJapan.     

Small mass lesions in cirrhosis: Transition from benign adenomatous hyperplasia to hepatocellular carcinoma?

Abstract Ten patients with cirrhosis, in whom small mass lesions were detected by imaging techniques and histological diagnosis of the resected specimens was difficult, are described. There were 17 grossly discrete lesions measuring 10 × 8 mm to 27 × 22 mm. Four were compatible with so-called adenomatous hyperplasia showing no histological features of malignancy, and eight were equivocal as to whether they were benign or malignant. The other five lesions (in four patients) were hepatocellular carcinoma, co-existing with apparently benign lesions. The eight equivocal lesions were eventually judged to be highly differentiated hepatocellular carcinomas. These benign-appearing lesions, found by advanced imaging in patients with cirrhosis, create a serious problem in regions where primary liver cancer is endemic among cirrhotics, and hepatic resection is the preferred treatment.
It is possible that these lesions represent a transition from adenomatous hyperplasia occurring in cirrhotic livers to hepatocellular carcinoma through a histologically equivocal state and that the current morphological methods are inadequate for differentiating malignant from benign lesions.