Ghrelin is a novel growth hormone؊releasing peptide isolated from human and rat stomach that induces weight gain by increasing food intake and reducing fat utilization. Although recent data indicate that ghrelin is downregulated in human adult obesity, the characteristics of human obesity are heterogeneous, especially in children and adolescents, and depend on the distribution of subcutaneous and visceral fat tissue. We measured fasting plasma ghrelin concentrations by radioimmunoassay in 49 obese Japanese children and adolescents (38 boys and 11 girls; mean age 10.2 ؎ 2.8 years; BMI 28.0 ؎ 4.5 kg/m 2 , percent overweight 56.0 ؎ 20.7%), and analyzed associations of their ghrelin concentrations with their body composition, insulin resistance, and adipocytokine concentrations. Fasting plasma ghrelin levels were negatively correlated with BMI and waist circumference, but not with percent overweight or percent body fat, whereas fasting leptin levels were positively correlated with all of the following parameters: BMI, waist circumference, percent overweight, and percent body fat. Plasma ghrelin levels were negatively correlated with fasting immunoreactive insulin, homeostasis model assessment insulin resistance index, and quantitative insulin sensitivity check index values. There was no correlation between plasma ghrelin and leptin, but ghrelin was negatively correlated with the PAI-1 concentrations. The results suggest that the downregulation of ghrelin secretion may be a consequence of higher insulin resistance associated with visceral fat accumulation and elevated PAI-1 concentrations, and not a consequence of total body fat accumulation associated with elevated leptin concentrations.

Among 579 autopsy cases of hepatocellular carcinoma (HCC), 55 cases (9.4%) exhibited a sarcomatous appearance. The incidence of HCC with a sarcomatous appearance has been increasing over the past 17 years. A sarcomatous appearance was found in 20 out of 335 autopsy cases of HCC (5.9%) during the 12 years from 1969 to 1980, and in 35 out of 244 autopsy cases of HCC (14.3%) during the last 6 years, when effective anticancer therapies, such as the one-shot injection of anticancer agents into the hepatic artery (one-shot therapy) and transcatheter arterial embolization (TAE), have become popular. A sarcomatous appearance was found in 20.9% of the cases undergoing anticancer therapy and in 4.2% of the cases not undergoing anticancer therapy. Among the various anticancer therapies, the sarcomatous appearance was most frequent (27.6%) in cases with repeated TAE. Thus, a close relationship between the sarcomatous appearance in HCC and anticancer therapies was suggested. Regarding the development of the sarcomatous appearance, we presume that it may be caused by the phenotypic change of HCC cells caused by anticancer therapy, or that a number of factors, including anticancer therapy, may accelerate the proliferation of the sarcomatous cells existing in the original tumor as one of the histological components. In order to clarify the true nature of sarcomatous lesions in HCC, further histological and biological studies are required.

Some surgically resected small hepatocellular carcinoma (HCC) up to 2 cm in diameter have indistinct margins, and it is sometimes difficult to identify the margins of the cancer nodule in the resected specimen. We classified such tumors as small HCC with indistinct margins and carried out a morphological study to define their characteristics in comparison with small HCC with distinct margins as a control group. We have encountered 27 examples among 86 tumors smaller than 2.0 cm in diameter. The tumors of this type indistinctly retained the basic architecture of the background and were vaguely demarcated. Most tumors were uniformly composed of well-differentiated cancer tissue, which is characterized by increased cell density with increased nuclear/cytoplasm ratio, increased cytoplasmic eosinophilia, and irregular thin-trabecular pattern with occasional pseudoglandular pattern. Portal tracts were included within the cancerous tissue. There was a "replacing" growth pattern at the tumor/nontumor boundary. Four of the 27 lesions had a nodule-in-nodule appearance, and the inner nodules consisted of moderately differentiated HCC without portal tracts. In all of the small HCC with indistinct margins, tumor invasion into the portal vein and intrahepatic metastasis were not found. In a control group, the tumors were well-demarcated, and 53% of them were encapsulated. They were well-differentiated in 9, moderately differentiated in 38 and mixed well and moderately in 12. Tumor invasion into the portal vein and intrahepatic metastasis was found in 16 (27.1%) and 6 (10.2%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The Committee of the Japan Society for the Study of Obesity reported the new criteria for 'obesity disease' for Japanese adults in 2000. We defined the criteria for the diagnosis of obesity in children with medical problems, corresponding to the 'obesity disease' criteria in adults. Obesity in childhood was defined as follows: percentage of overweight (POW) and body fat exceeded the criteria. 'Obesity disease in childhood' was defined as obesity associated with health or medical problems, and with indications for medical intervention. Medical problems with indications for immediate intervention were grouped as A problems, which consisted of (i). hypertension; (ii). sleep apnea or hypoventilation; (iii). Type 2 diabetes mellitus or impaired glucose tolerance; and (iv). increased waist circumference or accumulation of visceral adipose tissue. Metabolic derangements or equivalent associated with obesity were grouped as B problems: (i). liver dysfunction; (ii). hyperinsulinemia; (iii). hypercholesterolemia; (iv). hypertriglyceridemia; (v). low serum high-density lipoprotein cholesterol; (vi). acanthosis nigricans, and (vii). hyperuricemia. Obese children over 5 years of age with following conditions were diagnosed as 'obesity disease in childhood': (i). any 'A problem', (ii) POW >or= 50% and any 'B problem', or (3) POW < 50% and more than one 'B problem' or equivalent. We decided to take physicosocial problems related to obesity into consideration as the criteria. The resultant criteria are proposed by the Committee for Research of Appropriate Body Build in Children*.

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