Association of multiple liver cell adenomas with spontaneous intrahepatic portohepatic shunt

The association of multiple liver cell adenomas containing foci of focal nodular hyperplasia with a spontaneous intrahepatic portohepatic venous shunt is reported in a 13-year-old male patient. At least eight nodules less than 10 cm in diameter were recognized and proved by means of surgical resection or surgical biopsies. These lesions were heterogeneous and hypodense on precontrast computed tomographic (CT) scans, and were slightly enhanced after injection of contrast medium. At magnetic resonance (MR) imaging, the signal intensity of these nodules varied. It was either hyperintense or hypointense on T1-weighted SE images. Sonography and angiography demonstrated a portohepatic venous shunt and hepatic arterialization was observed. These findings emphasize the hypothesis that hepatic arterialization may cause the development of liver cell adenomas. Moreover, it is suggested that liver cell adenoma and focal nodular hyperplasia have a common pathogenesis.     

Blastomycosis in a young African man presenting with a pleural effusion

Blastomyces dermatitidis is a dimorphic fungus endemic to northwestern Ontario, Manitoba and some parts of the United States. The fungus is also endemic to parts of Africa. Pulmonary and extrapulmonary findings of a 24-year-old African man who presented with weight loss, dry cough and chronic pneumonia not resolving with antibiotic treatment are presented. The unusual occurrence of pulmonary blastomycosis associated with skin lesions and a moderate pleural effusion is reported.     

Relation between hepatocarcinoma and hepatitis C virus infection

The incidence of hepatocarcinoma (HCC) has increased in industralized countries. Its relation with hepatitis C virus (HCV) has already been established. The mechanisms by which HCV promotes HCC development are poorly understood. The continuous necrotic and inflammatory effect with subsequent liberation of various cytoquines and modifications in hepatocyte genome have been proposed. Chronic infection with HCV leads to chronic liver disease and cirrhosis which is described as the main precursory lesion to HCC. The assessment methods for patients with chronic liver diseases allow those patients with high risk for HCC to be identified and the process to identify this tumor at an early stage to be initiated.     

Liver diseases in Mexico and their associated mortality trends from 2000 to 2007: A retrospective study of the nation and the federal states

Introduction. Liver disease is a major health issue in Mexico. Although several studies have been performed to analyze the impact of liver diseases on the Mexican population, none has compared the prevalence and impact of liver disease between states within Mexico. AIM: To analyze trends in mortality associated with liver diseases from 2000 to 2007 at the national and state levels.Methods. Data was obtained from the Ministry of Health (number of deaths) and the National Population Council (CONAPO) (population at risk) and mortality rates were analyzed using statistical software.Results. Mortality due to viral hepatitis, liver tumors, and cirrhosis increased over the study period. Alcohol-related mortality decreased but was still the main cause of liver-related deaths. Viral hepatitis infection occurred predominantly in the northern states and liver tumors occurred predominantly in the central region. Alcohol-related deaths were elevated along the Pacific shoreline and deaths associated with cirrhosis occurred mainly in the central and southern states.Conclusion. Incidence of liver-related mortality has increased and will continue to do so in the future.     

Mortality trends for liver cancer in Mexico from 2000 to 2006

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with an estimated incidence of half a million new cases per year around the world. Furthermore, HCC is the third greatest cause of cancer-related death in the world, and most of these deaths are registered in developing countries. Recently it has been suggested that Hispanics in the United States have high rates of HCC, but no information regarding this is available in Mexico. The aim of this study was to investigate recent trends (2000-2006) in HCC mortality rates in Mexico. Methods. Data on national mortality (death certificates) reported for the years 2000-2006 by the Health Ministry of Mexico were analyzed (www.salud.gob.mx). HCC as a cause of death was analyzed. Mortality rates were calculated for all population ages. Causes of death related to HCC were selected in accordance with the International Classification of Diseases, 10th Revision, Liver Cancer (C22.0, C22.7, C22.9). Results. We found that age-adjusted mortality rates were remarkably higher in men than in women in the period 2000-2006. In addition, we found an increase in the general mortality rates of HCC from 4.1 per 100,000 in 2000 to 4.7 per 100,000 in 2006. Conclusions. The results of this study suggest an increase in the mortality rate for HCC in the period 2000-2006. HCC will become a significant cause of morbidity and mortality in the near future.     

Role of smooth muscle cells in the initiation and early progression of atherosclerosis

The initiation of atherosclerosis results from complex interactions of circulating factors and various cell types in the vessel wall, including endothelial cells, lymphocytes, monocytes, and smooth muscle cells (SMCs). Recent reviews highlight the role of activated endothelium and inflammatory cell recruitment in the initiation of and progression of early atherosclerosis. Yet, human autopsy studies, in vitro mechanistic studies, and in vivo correlative data suggest an important role for SMCs in the initiation of atherosclerosis. SMCs are the major producers of extracellular matrix within the vessel wall and in response to atherogenic stimuli can modify the type of matrix proteins produced. In turn, the type of matrix present can affect the lipid content of the developing plaque and the proliferative index of the cells that are adherent to it. SMCs are also capable of functions typically attributed to other cell types. Like macrophages, SMCs can express a variety of receptors for lipid uptake and can form foam-like cells, thereby participating in the early accumulation of plaque lipid. Like endothelial cells, SMCs can also express a variety of adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 to which monocytes and lymphocytes can adhere and migrate into the vessel wall. In addition, through these adhesion molecules, SMCs can also stabilize these cells against apoptosis, thus contributing to the early cellularity of the lesion. Like many cells within the developing plaque, SMCs also produce many cytokines such as PDGF, transforming growth factor-beta, IFNgamma, and MCP-1, all of which contribute to the initiation and propagation of the inflammatory response to lipid. Recent advances in SMC-specific gene modulation have enhanced our ability to determine the role of SMCs in early atherogenesis.     

First 100 Cases With Doppler-Guided Hemorrhoidal Artery Ligation

Purpose This study was designed to examine the benefits of a Doppler-guided hemorrhoidal artery ligation technique in terms of surgical outcome, functional recovery, and postoperative pain. Methods Using local, regional, or general anesthesia, 100 patients with symptomatic Grades II or III hemorrhoids underwent sonographic identification and suture ligation of six to eight terminal branches of the superior rectal artery above the dentate line. Visual Analog Scales were used for postoperative pain scoring. Surgical and functional outcomes were assessed at 6 weeks and 3, 6, and 12 months after surgery. Results There were 42 (42 percent) males and 58 (58 percent) females (mean age, 42 years; median duration of symptoms, 6.3 years). The mean operative time was 19 minutes. Local anal block combined with intravenous sedation (n = 93) or general or spinal (n = 7) anesthesia was used. Only five were hospitalized overnight. There was no urinary retention, bleeding, or mortality in the immediate postoperative course. The mean pain score decreased from 2.1 at two hours postoperative to 1.3 on the first postoperative day. All patients had a complete functional recovery by the third postoperative day. Ninety-four patients remained asymptomatic after a mean follow-up of six months: four patients required additional surgical excision, and two required rubber band ligations for persistent bleeding. On follow-up, there was no report of incontinence to gas or feces, fecal impaction, or persistent pain. Conclusions Our experience indicates that Doppler-guided hemorrhoidal artery ligation is safe and effective and can be performed as an outpatient procedure with local or regional anesthesia and with minimal postoperative pain and early recovery. Reprints are not available.     

Population distribution of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C risk alleles for methotrexate toxicity in Israel

Methylenetetrahydrofolate reductase (MTHFR) is a central regulatory enzyme in the folate pathway. Two non-synonymous single nucleotide polymorphisms in MTHFR, C677T (rs1801133) and A1298C (rs1801131) have been associated with reduced MTHFR enzyme activity. These polymorphisms, especially C677T, appear to be linked with methotrexate-related toxicity, particularly hepatotoxicity; thus, pretreatment identification of individuals carrying these polymorphisms may be of clinical relevance. The purpose of this study was to determine the frequency and distribution of MTHFR polymorphic variants, known to functionally impair MTHFR activity, in the highly heterogeneous Israeli population. MTHFR genotyping was carried out in the representatives of three major demographic groups in Israel by PCR–restriction fragment length polymorphism and high-resolution melting. The relative distribution of variant alleles 677T and 1298C was found to be similar in individuals of Jewish, Druze and Arab Moslem descent (p = 0.09). However, Ashkenazi Jews displayed a 1.9-fold higher frequency of variant 677T and a 1.8-fold lower frequency of variant 1298C compared to non-Ashkenazi Jews (p < 0.001). Distinct differences in the relative frequencies of both polymorphisms were also found between Ashkenazi Jews and Druze (p < 0.01 for C677T, p < 0.01 for A1298C) or Ashkenazi Jews and Arab Moslem (p < 0.01 for C677T, p < 0.05 for A1298C). These data underscore the importance of geographic genetic analysis for a better understanding of human pharmacotherapy and personalized medicine.     

Insulin stimulates IGFBP-2 expression in 3T3-L1 adipocytes through the PI3K/mTOR pathway

Insulin-like growth factor binding protein 2 (IGFBP-2) has been implicated in the etiology of several diseases, including the metabolic syndrome. Although IGFBP-2 derives mostly from the liver, recent evidence in mice and humans indicate that aging and obesity are associated with altered IGFBP-2 levels in white adipocytes. The present study was aimed at determining the mechanisms that control IGFBP-2 expression in mature adipocytes. IGFBP-2 mRNA and protein expression in serum-deprived 3T3-L1 adipocytes were twofold increased by acute insulin treatment. Co-treatments with the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin or the mammalian target of rapamycin (mTOR) inhibitor rapamycin blunted the effects of insulin. Coherently, IGFBP-2 mRNA levels were robustly increased in adipocytes lacking either TSC2 or 4E-BP1. Insulin triggered the recruitment of CAAT/enhancer binding protein α (C/EBPα) to the IGFBP-2 proximal promoter. These findings suggest that insulin upregulates IGFBP-2 expression through a PI3K/mTOR/C/EBPα pathway in white adipocytes.     

Distinct perturbation of the translatome by the antidiabetic drug metformin

Metformin has been reported to lower cancer incidence among type II diabetics. Metformin exhibits antiproliferative and antineoplastic effects associated with inhibition of mammalian target of rapamycin complex 1 (mTORC1), but the mechanisms are poorly understood. We provide a unique genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) compared with metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's antiproliferative activity can be explained by selective translational suppression of mRNAs encoding cell-cycle regulators via the mTORC1/eukaryotic translation initiation factor 4E-binding protein pathway. Thus, metformin selectively inhibits translation of mRNAs encoding proteins that promote neoplastic proliferation, which should facilitate studies on metformin and related biguanides in cancer prevention and treatment.