In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.

The tumor suppressor gene p16 (CDKN2/MTS-1/ INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations by: methylation-speci®c PCR (MSP) to determine the methylation status of the p16 promoter region; comparative multiplex PCR to detect homozygous deletion; PCR ± SSCP and DNA sequencing analysis to identify mutation of the p16 gene. We found high frequency of hypermethylation of the 5' CpG island of the p16 gene in 30 of 48 cases (62.5%) of HCC tumors. Moreover, homozygous deletion at p16 region were present in ®ve of 48 cases (10.4%); and missense mutation were detected in three of 48 cases (6.3%). The overall frequency of p16 alterations, including homozygous deletion, mutation and hypermethylation, in HCC tumors was 70.8% (34 of 48 cases). These ®ndings suggest that: (a) the inactivation of the p16 is a frequent event in HCC; (b) the p16 gene is inactivated by multiple mechanisms including homozygous deletion, promoter hypermethylation and point mutation; (c) the most common somatic alteration of the p16 gene in HCC is de novo hypermethylation of the 5' CpG island; and (d) in contrast to other studies, high frequency of genomic alterations are not uncommon in the 9p21 of the p16 gene. Our results strongly suggest that the p16 gene plays an important role in the pathogenesis of HCC.

Thioacetamide (TAA) administration is an established technique for generating rat models of liver fibrosis and cirrhosis. Oxidative stress is believed to be involved as TAA-induced liver fibrosis is initiated by thioacetamide S-oxide, which is derived from the biotransformation of TAA by the microsomal flavine-adenine dinucleotide (FAD)-containing monooxygense (FMO) and cytochrome P450 systems. A two-dimensional gel electrophoresis-mass spectrometry approach was applied to analyze the protein profiles of livers of rats administered with sublethal doses of TAA for 3, 6 and 10 weeks respectively. With this approach, 59 protein spots whose expression levels changed significantly upon TAA administration were identified, including three novel proteins. These proteins were then sorted according to their common biochemical properties and functions, so that pathways involved in the pathogenesis of rat liver fibrosis due to TAA-induced toxicity could be elucidated. As a result, it was found that TAA-administration down-regulated the enzymes of the primary metabolic pathways such as fatty acid beta-oxidation, branched chain amino acids and methionine breakdown. This phenomenon is suggestive of the depletion of succinyl-CoA which affects heme and iron metabolism. Up-regulated proteins, on the other hand, are related to oxidative stress and lipid peroxidation. Finally, these proteomics data and the data obtained from the scientific literature were integrated into an "overview model" for TAA-induced liver cirrhosis. This model could now serve as a useful resource for researchers working in the same area.

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The severity of hepatocellular carcinoma (HCC) and the lack of good diagnostic markers and treatment strategies have rendered the disease a major challenge. Previous microarray analyses of HCC were restricted to the selected tissue sample sets without validation on an independent series of tissue samples. We describe an approach to the identification of a composite discriminator cassette by intersecting different microarray datasets. We studied the global transcriptional profiles of matched HCC tumor and nontumor liver samples from 37 patients using cDNA (cDNA) microarrays. Application of nonparametric Wilcoxon statistical analyses (P < 1 ؋ 10 ؊6 ) and the criteria of 1.5-fold differential gene expression change resulted in the identification of 218 genes, including BMI-1, ERBB3, and those involved in the ubiquitin-proteasome pathway. Elevated ERBB2 and epidermal growth factor receptor (EGFR) expression levels were detected in ERBB3-expressing tumors, suggesting the presence of ERBB3 cognate partners. Comparison of our dataset with an earlier study of approximately 150 tissue sets identified multiple overlapping discriminator markers, suggesting good concordance of data despite differences in patient populations and technology platforms. These overlapping discriminator markers could distinguish HCC tumor from nontumor liver samples with reasonable precision and the features were unlikely to appear by chance, as measured by Monte Carlo simulations. More significantly, validation of the discriminator cassettes on an independent set of 58 liver biopsy specimens yielded greater than 93% prediction accuracy. In conclusion, these data indicate the robustness of expression profiling in marker discovery using limited patient tissue specimens as well as identify novel genes that are highly likely to be excellent markers for HCC diagnosis and treatment. Supplementary material for this article can be found on the HEPATOLOGY website H epatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver that accounts for more than 70% of liver cancers worldwide. 1 A major risk factor associated with the development of HCC is hepatitis B virus (HBV) infection. Death is usually due to liver failure associated with cirrhosis and/or rapid outgrowth of multiple nodules. Approximately 0.25 to 1 million new cases of HCC are diagnosed each year, and the cancer is especially prevalent in Southeast Asia, China, and sub-Saharan Africa. Although surgical resection is considered to be the main curative treatment, only 10% to 15% of cases are suitable for surgery at the time of presentation. This is because either the disease is detected at an advanced stage at presentation or the underlying poor liver functional reserve precluded surgical intervention.The lack of molecular markers that characterize tumor formation poses a major problem to effective diagnosis and prognosis of HCC. Current diagnosis of HCC relies on the presence of a liver mass on radiologic investigations and the detection of an elevated level of serum al...

The need for healthcare workers (HCWs) to wear personal protective equipment (PPE) during the coronavirus disease 2019 (COVID-19) pandemic heightens their risk of thermal stress. We assessed the knowledge, attitudes, and practices of HCWs from India and Singapore regarding PPE usage and heat stress when performing treatment and care activities. One hundred sixty-five HCWs from India (n = 110) and Singapore (n = 55) participated in a survey. Thirty-seven HCWs from Singapore provided thermal comfort ratings before and after ice slurry ingestion. Differences in responses between India and Singapore HCWs were compared. A p-value cut-off of 0.05 depicted statistical significance. Median wet-bulb globe temperature was higher in India (30.2 °C (interquartile range [IQR] 29.1–31.8 °C)) than in Singapore (22.0 °C (IQR 18.8–24.8 °C)) (p < 0.001). Respondents from both countries reported thirst (n = 144, 87%), excessive sweating (n = 145, 88%), exhaustion (n = 128, 78%), and desire to go to comfort zones (n = 136, 84%). In Singapore, reports of air-conditioning at worksites (n = 34, 62%), dedicated rest area availability (n = 55, 100%), and PPE removal during breaks (n = 54, 98.2%) were higher than in India (n = 27, 25%; n = 46, 42%; and n = 66, 60%, respectively) (p < 0.001). Median thermal comfort rating improved from 2 (IQR 1–2) to 0 (IQR 0–1) after ice slurry ingestion in Singapore (p < 0.001). HCWs are cognizant of the effects of heat stress but might not adopt best practices due to various constraints. Thermal stress management is better in Singapore than in India. Ice slurry ingestion is shown to be practical and effective in promoting thermal comfort. Adverse effects of heat stress on productivity and judgment of HCWs warrant further investigation.

Acute appendicitis in the elderly is still associated with significant morbidity. But once acute appendicitis is diagnosed, then expedient surgery, appropriate use of perioperative antibiotics and a right lower quadrant incision can help to minimize the morbidity. Pre-existing severe comorbid medical condition(s) is a major contributory factor to mortality in these patients.

Proteome analysis of human hepatocellular carcinoma tissues was conducted using two-dimensional difference gel electrophoresis coupled with mass spectrometry. Paired samples from the normal and tumor region of resected human liver were labeled with Cy3 and Cy5, respectively while the pooled standard sample was labeled with Cy2. After analysis by the DeCyder software, protein spots that exhibited at least a two-fold difference in intensity were excised for in-gel tryptic digestion and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. A total of 6 and 42 proteins were successfully identified from the well- and poorly-differentiated samples, respectively. The majority of these proteins are related to detoxification/oxidative stress and metabolism. Three down-regulated metabolic enzymes, methionine adenosyltransferase, glycine N-methyltransferase, and betaine-homocysteine S-methyltransferase that are involved in the methylation cycle in the liver are of special interest. Their expression levels, especially, methionine adenosyltransferase, seemed to have a major influence on the level of S-adenosylmethionine (AdoMet), a vital intermediate metabolite required for the proper functioning of the liver. Recent work has shown that chronic deficiency in AdoMet in the liver results in spontaneous development of steatohepatitis and hepatocellular carcinoma, and hence the down-regulation of hepatic methionine adenosyltransferase in our hepatocellular carcinoma samples is in line with this observation. Moreover, when a comparison is made between the differentially expressed proteins from our human hepatocellular carcinoma samples and from the liver tissues of knockout mice deficient in methionine adenosyltransferase, there is a fairly good correlation between them.