No abstract

The results of hepatic resection in 229 patients with HCC were analyzed. Child's class, BSP test, and blood loss during surgery were good predictors for operative death. The 5- and 10-year survival rates were 26.4% and 19.4%, respectively. Age, liver cirrhosis, tumor size, and postoperative chemotherapy were prognostic factors. Multidisciplinary approach with liver resection, postoperative chemotherapy, and liver transplantation will be a realistic direction for the surgical treatment of HCC in future.

The regenerative process was evaluated in terms of liver size, function, and histology in 28 adults who had major hepatic resection: hepatocellular carcinoma (HCC) in 21, secondary liver cancer from colorectum in four, carcinoma of the gallbladder in one, Klatskin tumor in one, and Caroli's disease in one. There were 22 men and six women. Ages ranged from 17 to 74 years with a mean age of 56.7. All patients with HCC had underlying liver disease: liver cirrhosis in 14 and chronic hepatitis in seven. Extended right lobectomy was done on 10 patients, right lobectomy on 16 patients, and left lobectomy on two patients. The residual liver size was serially estimated with computed tomography (CT) in 15 patients: six with normal liver, five with chronic hepatitis, and four with cirrhosis. A complete restoration of the residual liver size was found within 3 months in 3 and 6 months, respectively, in two patients with normal livers. The liver was enlarged in all patients with the parenchymal diseases but obviously more slowly compared with normal liver. Liver functions were restored normally within 2-3 weeks in patients with normal livers, but hyperbilirubinemia persisted longer in those with chronic hepatitis and cirrhosis. A continuous rise of bilirubin was an ominous sign of liver failure and subsequent death, which occurred in five patients with cirrhosis. Serum alpha-fetoprotein did not rise in accordance with the regeneration. Histologically, evidence of active regeneration with increased mitotic activity was found at 10 and 35 days in those patients with normal livers. Mitosis was not seen in a specimen taken at 7 days. Enlarged cuboidal hepatocytes and cells with basophilic cytoplasm or two nuclei were observed more or less in all specimens. The livers with cirrhosis or hepatitis also showed histologic evidence of regeneration during the first 2 months but substantially less compared with normal liver, which was well supported by the volumetric study of the liver remnants with CT.

We tried to determine the role of the body mass index (BMI) on the extent of lymph node dissection in gastric cancer surgery. Seven hundred and eighty-seven patients with gastric carcinoma were reviewed. Ninety-two (11%) patients exceeded the upper limit of the optimum BMI. Significantly fewer lymph nodes were removed following D2 (p = 0.002) and ≥D3 (p = 0.023) dissections, and the lymph node ratio was significantly (p = 0.0383) higher in overweight patients. The recurrence-free survival was significantly (p = 0.0297) shorter in T2/T3 cases with high BMI, and BMI (relative risk 1.85) became an independent prognostic factor in multivariate analysis. Higher BMI hampers regional lymph node dissection in gastric cancer patients and became an independent predictor of disease recurrences in T2/T3 gastric cancers.

Cretinism is marked by irreversible mental and growth retardation. We describe here an entirely new case of cretinism showing combined pituitary hormone deficiencies of thyrotropin, growth hormone and prolactin that appears to be caused by homozygosity for a nonsense mutation in the gene for the pituitary specific transcription activator, Pit-1/GHF-1 (designated PIT1 in humans for pituitary specific factor 1). This is the first report in humans of a defect in a transcription activator causing deficiency of multiple target genes.

FOXP3/Scurfin, a member of forkhead/winged-helix proteins, is involved in the regulation of T-cell activation, and essential for normal immune homeostasis. The FOXP3/Scurfin gene is located on chromosome Xp11.23, which includes one of the type 1 diabetes susceptible loci. Therefore, we investigated whether the human FOXP3/Scurfin gene might be a new candidate gene for type 1 diabetes. We first screened the human FOXP3/Scurfin gene for microsatellite and single nucleotide polymorphisms. Next, we performed an association study between the FOXP3/Scurfin gene and type 1 diabetes. Then, the evaluation of promoter/enhancer activity of the intron with (GT)(n) polymorphism was performed by dual luciferase reporter assay. We demonstrated two regions contained microsatellite polymorphisms; one was (GT)(n), located on intron zero and the other (TC)(n) on intron 5, which were under linkage-disequilibrium. The (GT)(15) allele showed a significantly higher frequency in patients with type 1 diabetes than in controls (43.1% vs 32.6%, P=0.0027). The genotype frequencies of (GT)(15)/(GT)(15) in female patients and of (GT)(15) in male patients tended to be higher than those in female ( P=0.064) and male ( P=0.061) controls, respectively. A significant difference in the enhancer activity between (GT)(15) and (GT)(16) dinucleotide repeats was detected. In conclusion, the FOXP3/Scurfin gene appears to confer a significant susceptibility to type 1 diabetes in the Japanese population.

Purpose: Angiogenesis plays an important role in a multitude of biological processes including those of tumorigenesis and cancer progression. Hypoxia is the prime driving factor for tumor angiogenesis and the family of hypoxiainducible factors (HIFs) plays a pivotal role in this process. The role of HIF in tumor angiogenesis has been underscored in different carcinomas but yet to be reported for colorectal carcinomas.Experimental Design: In this study, we examined HIF [HIF-1␣ (HIF1) and HIF-2␣ (HIF2)] expression in 87 curatively resected colorectal carcinoma samples, and the results were correlated with clinicopathological factors, microvessel density, cyclooxygenase 2 expression, and patient prognosis.Results: HIF1 (44.8%) was more frequently expressed than HIF2 (29.9%). Most of the clinicopathological factors representing the tumor aggressiveness were significantly correlated with overexpression of HIF2 but not with HIF1 expression. HIF2 expression had direct correlation with microvessel density and cyclooxygenase 2 expression. and, in contrast, HIF1 expression had a weak but significant inverse correlation in T 1 and T 2 tumors only. HIF2 expression alone and the combined expression of HIF1 and HIF2 had significant impact on patient survival. In the multivariate analysis, however, only the combined expression of HIF1 and HIF2 remained independently significant.Conclusions: Taken together, our results suggest that HIF2 expression may play an important role in angiogenesis and that the combined expression of HIF1 and HIF2 may play an important role in tumor progression and prognosis of colorectal carcinomas. Therefore, HIF expression could be a useful target for therapeutic intervention.

In the treatment of HCC without cirrhosis, major hepatectomy is advocated to prevent early recurrence. Liver transplantation may be required for patients with HCV infection.