Characteristics of gastric cancer in Asia

Gastric cancer(GC)is the fourth most common cancer in the world with more than 70%of cases occur in the developing world.More than 50%of cases occur in Eastern Asia.GC is the second leading cause of cancer death in both sexes worldwide.In Asia,GC is the third most common cancer after breast and lung and is the second most common cause of cancer death after lung cancer.Although the incidence and mortality rates are slowly declining in many countries of Asia,GC still remains a significant public health problem.The incidence and mortality varies according to the geographic area in Asia.These variations are closely related to the prevalence of GC risk factors;especially Helicobacter pylori(H.pylori)and its molecular virulent characteristics.The gradual and consistent improvements in socioeconomic conditions in Asia have lowered the H.pylori seroprevalence rates leading to a reduction in the GC incidence.However,GC remains a significant public health and an economic burden in Asia.There has been no recent systemic review of GC incidence,mortality,and H.pylori molecular epidemiology in Asia.The aim of this report is to review the GC incidence,mortality,and linkage to H.pylori in Asia.

Non-alcoholic fatty liver disease and the metabolic syndrome:An update

Sedentary lifestyle and poor dietary choices are leading to a weight gain epidemic in westernized countries, subsequently increasing the risk for developing the metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). NAFLD is estimated to affect approximate 30% of the general US population and is considered the hepatic manifestation of the metabolic syndrome. Recent findings linking the components of the metabolic syndrome with NAFLD and the progression to nonalcoholic steatohepatitis (NASH) will be reviewed; in particular, the role of visceral adipose tissue, insulin resistance, and adipocytokines in the exacerbation of these conditions. While no therapy has been proven effective for treating NAFLD/NASH, common recommendations will be discussed.

Staging accuracy of esophageal cancer by endoscopic ultrasound:A meta-analysis and systematic review

AIM: To evaluate the accuracy of endoscopic ultrasound (EUS) in the staging of esophageal cancer. METHODS: Only EUS studies confirmed by surgery were selected. Articles were searched in Medline and Pubmed. Two reviewers independently searched and extracted data. Meta-analysis of the accuracy of EUS was analyzed by calculating pooled estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds ratio. Pooling was conducted by both the Mantel-Haenszel method (fixed effects model) and DerSimonian Laird method (random effects model). The heterogeneity of studies was tested using Cochran’s Q test based upon inverse variance weights. RESULTS: Forty-nine studies (n = 2558) which met the inclusion criteria were included in this analysis. Pooled sensitivity and specificity of EUS to diagnose T1 was 81.6% (95% CI: 77.8-84.9) and 99.4% (95% CI: 99.0-99.7), respectively. To diagnose T4, EUS had a pooled sensitivity of 92.4% (95% CI: 89.2-95.0) and specificity of 97.4% (95% CI: 96.6-98.0). With Fine Needle Aspiration (FNA), sensitivity of EUS to diagnose N stage improved from 84.7% (95% CI: 82.9-86.4) to 96.7% (95% CI: 92.4-98.9). The P value for the χ2 test of heterogeneity for all pooled estimates was > 0.10. CONCLUSION: EUS has excellent sensitivity and specificity in accurately diagnosing the TN stage of esophageal cancer. EUS performs better with advanced (T4) than early (T1) disease. FNA substantially improves the sensitivity and specificity of EUS in evaluating N stage disease. EUS should be strongly considered for staging esophageal cancer.

Acute fatty liver of pregnancy:An update on pathogenesis and clinical implications

Acute fatty liver of pregnancy (AFLP) is a serious maternal illness occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. Till recently, it has been considered a mysterious illness. In this editorial, we review the recent advances in understanding the pathogenesis of AFLP and discuss the studies documenting a fetal-maternal interaction with a causative association between carrying a fetus with a defect in mitochondrial fatty acid oxidation and development of AFLP. Further, we discuss the impact of these recent advances on the offspring born to women who develop AFLP, such that screening for a genetic defect can be life saving to the newborn and would allow genetic counseling in subsequent pregnancies. The molecular basis and underlying mechanism for this unique fetal-maternal interaction causing maternal liver disease is discussed.

How good is endoscopic ultrasound for TNM staging of gastric cancers? A meta-analysis and systematic review

AIM: To evaluate the accuracy of endoscopic ultrasound (EUS) for staging of gastric cancers. METHODS: Only EUS studies confirmed by surgery were selected. Only studies from which a 2 × 2 table could be constructed for true positive, false negative, false positive and true negative values were included. Articles were searched in Medline, Pubmed, Ovid journals, Cumulative index for nursing & allied health literature, International pharmaceutical abstracts, old Medline, Medline nonindexed citations, and Cochrane control trial registry. Two reviewers independently searched and extracted data. The differences were resolved by mutual agreement. 2 × 2 tables were constructed with the data extracted from each study. Meta-analysis for the accuracy of EUS was analyzed by calculating pooled estimates of sensitivity, specifi city, likelihood ratios, and diagnostic odds ratio. Pooling was conducted by both the Mantel-Haenszel method (fi xed effects model) and DerSimonian Laird method (random effects model). The heterogeneity of studies was tested using Cochran's Q test based upon inverse variance weights. RESULTS: Initial search identified 1620 reference articles and of these, 376 relevant articles were selected and reviewed. Twenty-two studies (n = 1896) which met the inclusion criteria were included in this analysis. Pooled sensitivity of T1 was 88.1% (95% CI: 84.5-91.1) and T2 was 82.3% (95% CI: 78.2-86.0). For T3, pooled sensitivity was 89.7% (95% CI: 87.1-92.0). T4 hada pooled sensitivity of 99.2% (95% CI: 97.1-99.9). For nodal staging, the pooled sensitivity for N1 was 58.2% (95% CI: 53.5-62.8) and N2 was 64.9% (95% CI: 60.8-68.8). Pooled sensitivity to diagnose distant metastasis was 73.2% (95% CI: 63.2-81.7). The P for chi-squared heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION: EUS results are more accurate with advanced disease than early disease. If EUS diagnoses advanced disease, such as T4 disease, the patient is 500 times more likely to have true anatomic stage of T4 disease.

Nonalcoholic fatty liver disease and mitochondrial dysfunction

Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood. Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.

Liver diseases in pregnancy: Diseases not unique to pregnancy

Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver.Liver disease can cause significant morbidity and mortality in both pregnant women and their infants.Few challenges arise in reaching an accurate diagnosis in light of such physiological changes.Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment.Other challenges entail the methods of treatment and their safety for both the mother and the baby.This review summarizes liver diseases that are not unique to pregnancy.We focus on viral hepatitis and its mode of transmission,diagnosis,effect on the pregnancy,the mother,the infant,treatment,and breast-feeding.Autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,Wilson’s disease,Budd Chiari and portal vein thrombosis in pregnancy are also discussed.Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis.Variceal bleeding can happen in up to 38%of cirrhotic pregnant women.Management of portal hypertension during pregnancy is discussed.Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones.We discuss some of the interventions for gallstones in pregnancy if symptoms arise.Finally,we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy.

Utility of endoscopic ultrasound in patients with portal hypertension

Endoscopic ultrasound(EUS) has revolutionized the diagnostic and therapeutic approach to patients with gastrointestinal disorders. Its application in patients with liver disease and portal hypertension is increasing. Patients with chronic liver disease are at risk for development of portal hypertension sequale such as ascites, spontaneous bacterial peritonitis and gastroesophageal varices. Bleeding esophageal and gastric varices are among the most common causes of mortality in patients with cirrhosis. Thus, early detection and treatment improve the outcome in this population. EUS can improve the detection and diagnosis of gastroesophageal varices and collateral veins and can provide endoscopic therapy of gastroesophageal varices such as EUS-guided sclerotherapy of esophageal collateral vessels and EUS-guided cynoacrylate(Glue) injection of gastric varices. EUS can also provide knowledge on the efficacy of pharmacotherapy of portal hypertension. Furthermore, EUS can provide assessment and prediction of variceal recurrence after endoscopic therapy and assessment of portal hemodynamics such as E-Flow and Doppler study of the azygous and portal veins. Moreover, EUS-guided fine needle aspiration may provide cytologic diagnosis of focal hepatic tumors andanalysis of free abdominal fluid.Using specialized EUSguided needle biopsy,a sample of liver tissue can be obtained to diagnose and evaluate for chronic liver disease.EUS-guided fine needle injection can be used to study portal vein pressure and hemodynamics,and potentially could be used to assist in exact measurement of portal vein pressure and placement of intrahepatic portosystemic shunt.

Liver diseases in pregnancy: Diseases unique to pregnancy

Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver.Liver disease can cause significant morbidity and mortality in both pregnant women and their infants.This review summarizes liver diseases that are unique to pregnancy.We discuss clinical conditions that are seen only in pregnant women and involve the liver;from Hyperemesis Gravidarum that happens in 1out of 200 pregnancies and Intrahepatic Cholestasis of Pregnancy(0.5%-1.5%prevalence),to the more frequent condition of preeclampsia(10%prevalence)and its severe form;hemolysis,elevated liver enzymes,and a low platelet count syndrome(12%of pregnancies with preeclampsia),to the rare entity of Acute Fatty Liver of Pregnancy(incidence of 1 per 7270 to 13000deliveries).Although pathogeneses behind the development of these aliments are not fully understood,theories have been proposed.Some propose the special physiological changes that accompany pregnancy as a precipitant.Others suggest a constellation of factors including both the mother and her fetus that come together to trigger those unique conditions.Reaching a timely and accurate diagnosis of such conditions can be challenging.The timing of the condition in relation toward which trimester it starts at is a key.Accurate diagnosis can be made using specific clinical findings and blood tests.Some entities have well-defined criteria that help not only in making the diagnosis,but also in classifying the disease according to its severity.Management of these conditions range from simple medical remedies to measures such as immediate termination of the pregnancy.In specific conditions,it is prudent to have expert obstetric and medical specialists teaming up to help improve the outcomes.

Role of mitochondria in alcoholic liver disease

Alcohol abuse is the leading cause of liver related morbidity and mortality.Chronic or binge alcohol drinking causes hepatic steatosis which can develop to steatohepatitis,cirrhosis and ultimately hepatocellular carcinoma.The pathogenesis of alcoholic liver disease(ALD)is poorly characterized,however several recent studies point to a major role of mitochondria in this process.Mitochondria play a crucial role in cellular energy metabolism and in reactive species formation.Alcohol treatment causes mitochondrial DNA damage,lipid accumulation and oxidative stress.Studies in both animal models and in humans showed that alcohol administration causes changes in the mitochondrial morphology and function suggesting a role of these changes in the pathogenesis of ALD.We review recent findings on mechanisms by which alcohol negatively impacts mitochondrial biogenesis and function and we will discuss the specific intracellular pathways affected by alcohol consumption.Interestingly,recent findings indicate that a large number of mitochondrial proteins are acetylated and that mitochondrial proteins acetylation and sirtuins are modulated by alcohol.Un-derstanding the mechanisms behind alcohol mediated impaired mitochondrial biogenesis and function may help identify potential therapeutic targets for treating ALD in humans.

Sirtuins and nonalcoholic fatty liver disease

Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class Ⅲ histone/protein deacetylases. Sirtuins(SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function. Sirtuins have been shown to play a key role in the development and rescue of various metabolic diseases including non-alcoholic fatty liver disease(NAFLD). NAFLD is currently the most chronic liver disease due mainly to high-calorie consumption and lower physical activity. No pharmacological approach is available to treat NAFLD, the current recommended treatment are lifestyle modification such as weight loss through calorie restriction and exercise. Recent studies have shown downregulation of sirtuins in human as well as animal models of NAFLD indicating an important role of sirtuins in the dynamic pathophysiology of NAFLD. In this review, we highlight the recent knowledge on sirtuins, their role in NAFLD and their unique potential role as novel therapeutic target for NAFLD treatment.

Epigenetics of hepatocellular carcinoma:Role of microRNA

Hepatocellular carcinoma(HCC)represents a major form of primary liver cancer in adults.MicroRNAs(miRs),small non-coding single-stranded RNAs of 19-24nucleotides in length,negatively regulate the expression of many target genes at the post-transcriptional and/or translational levels and play a critical role in the initiation and progression of HCC.In this review we have summarized the information of aberrantly expressed miRs in HCC,their mechanism of action and relationship to cancer.The recent advances in HCC research reveal that miRs regulate expression of various oncogenes and tumor suppressor genes,thereby contributing to the modulation of diverse biological processes including proliferation,apoptosis,epithelial to mesenchymal transition and metastasis.From a clinical viewpoint,polymorphisms within miR-binding sites are associated with the risk of HCC.Polymorphisms in miR related genes have been shown to correlate with survival or treatment outcome in patients.Furthermore,the review focuses on the potential role of miRs as novel biomarkers and their translational applications for diagnosis and therapy in HCC.With further insights into miR deregulation in HCC,it is expected that novel miR-based therapeutics will arise.Also,we orient the readers to other reviews that may provide better understanding of miR research in HCC.

Effect of precut sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis:A systematic review and meta-analysis

AIM:To conduct a systemic review and meta-analysis to investigate the role of early precut technique.Multiple randomized controlled trails(RCTs)have reported conflicting results of the early precut sphincterotomy.METHODS:MEDLINE/PubMed,EMBASE,Cochrane Central Register of Controlled Trials and Database of Systematic Reviews,and recent abstracts from major conference proceedings were searched(June 2013).Randomized and non-randomized studies comparing early precut technique with prolonged standard methods were included.Pooled estimates of post-endoscopic retrograde cholangiopancreatography(ERCP)pancreatitis(PEP),cannulation and adverse events were analyzed by using odds ratio(OR).Random and fixed effects models were used as appropriate.Publication bias was assessed by funnel plots.Heterogeneity among studies was assessed by calculating I2 measure of inconsistency.RESULTS:Seven randomized and seven non-randomized trials met inclusion criteria.Meta-analysis of RCTs showed a decrease trend for PEP with early precut sphincterotomy but was not statistically significant(OR=0.58;95%CI:0.32-1.05;P=0.07).No heterogeneity was noted among the studies with I2 of 0%.CONCLUSION:Early precut technique for common bile duct cannulation decreases the trend of post-ERCP pancreatitis.

Usefulness of endoscopic ultrasound-guided fine needle aspiration in the diagnosis of hepatic, gallbladder and biliary tract Lesions

Endoscopic ultrasound(EUS)-guided fine needle aspira-tion(FNA) of the liver is a safe procedure in the diag-nosis and staging of hepatobiliary malignancies with a minimal major complication rate. EUS-FNA is useful for liver lesions poorly accessible to other imaging modali-ties of the liver. EUS-guided FNA of biliary neoplasia and malignant biliary stricture is superior to the con-ventional endoscopic brushing and biopsy.

Primary hepatocellular carcinoma and metabolic syndrome:An update

Hepatocellular carcinoma(HCC) is the most common primary liver malignancy. The incidence of hepatocellular carcinoma has increased dramatically by 80% over the past two decades in the United States. Numerous basic science and clinical studies have documented a strong association between hepatocellular carcinoma and the metabolic syndrome. These studies have documented that, in most patients, non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome, which may progress to hepatocellular carcinoma through the cirrhotic process. However, minority of patients with non-alcoholic fatty liver disease may progress to hepatocellular carcinoma without cirrhosis.This review summarizes the current literature of the link between hepatocellular carcinoma and metabolic syndrome with special emphasis on various components of the metabolic syndrome including risk of association with obesity, diabetes mellitus, hyperlipidemia,and hypertension. Current understanding of pathophysiology, clinical features, treatments, outcomes,and surveillance of hepatocellular carcinoma in the background of metabolic syndrome and non-alcoholic fatty liver disease is reviewed. With the current epidemic of metabolic syndrome, the number of patients with non-alcoholic fatty liver disease is increasing.Subsequently, it is expected that the incidence and prevalence of HCC will also increase. It is very important for the scientific community to shed more light on the pathogenesis of HCC with metabolic syndrome,both with and without cirrhosis. At the same time it is also important to quantify the risk of hepatocellular carcinoma associated with the metabolic syndrome in a prospective setting and develop surveillance recommendations for detection of hepatocellular carcinoma in patients with metabolic syndrome.

Endoscopic ultrasound:It’s accuracy in evaluating mediastinal lymphadenopathy? A meta-analysis and systematic review

AIM:To evaluate the accuracy of endoscopic ultrasound (EUS), EUS-fine needle aspiration (FNA) in evaluating mediastinal lymphadenopathy. METHODS:Only EUS and EUS-FNA studies confirmed by surgery or with appropriate follow-up were selected. Articles were searched in Medline, Pubmed, and Cochrane control trial registry. Only studies from which a 2 × 2 table could be constructed for true positive, false negative, false positive and true negative values were included. Two reviewers independently searched and extracted data. The differences were resolved by mutual agreement. Meta-analysis for the accuracy of EUS was analyzed by calculating pooled estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Pooling was conducted by both Mantel-Haenszel method (fixed effects model) and DerSimonian Laird method (random effects model). The heterogeneity of studies was tested using Cochran’s Q test based upon inverse variance weights. RESULTS:Data was extracted from 76 studies (n = 9310) which met the inclusion criteria. Of these, 44 studies used EUS alone and 32 studies used EUS-FNA. FNA improved the sensitivity of EUS from 84.7% (95% CI:82.9-86.4) to 88.0% (95% CI:85.8-90.0). With FNA, the specificity of EUS improved from 84.6% (95% CI:83.2-85.9) to 96.4% (95% CI:95.3-97.4). The P forchi-squared heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION:EUS is highly sensitive and specific for the evaluation of mediastinal lymphadenopathy and FNA substantially improves this. EUS with FNA should be the diagnostic test of choice for evaluating mediastinal lymphadenopathy.

Role of the JNK signal transduction pathway in inflammatory bowel disease

The c-Jun NH2-terminal Kinase (JNK) pathway representsone sub-group of the mitogen-activated protein (MAP)kinases which plays an important role in variousinflammatory diseases states, including inflammatorybowel disease (IBD). Significant progress towardsunderstanding the function of the JNK signaling pathwayhas been achieved during the past few years. Blockadeof the JNK pathway with JNK inhibitors in animal modelsof IBD lead to resolution of intestinal inflammation.Current data suggest specific JNK inhibitors hold promiseas novel therapies in IBD.

Endoscopic assessment and management of early esophageal adenocarcinoma

Esophageal carcinoma affects more than 450000people worldwide and the incidence is rapidly increasing.In the United States and Europe,esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence.Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages.Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus.These risk factors include chronic gastroesophageal reflux disease,hiatal hernia,advanced age,male sex,white race,cigarette smoking,and obesity.The annual risk of esophageal cancer is approximately 0.25%for patients without dysplasia and 6%for patients with high-grade dysplasia.Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa.The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option.The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia.Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation,photodynamic therapy and cryoablation.Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion.Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor,positive lymph node and submucosal invasion.Surgical resection should be offered to patients with deep submucosal invasion.

Fatty liver without a large“belly”:Magnified review of nonalcoholic fatty liver disease in non-obese patients

Nonalcoholic fatty liver disease(NAFLD) is well described as a common cause of chronic liver disease, mostly in the obese population. It refers to a spectrum of chronic liver disease that starts with simple steatosis than progresses to nonalcoholic steatohepatitis and cirrhosis in patients without significant alcohol consumption. NAFLD in the non-obese population has been increasingly reported and studied recently. The pathogenesis of nonobese NAFLD is poorly understood and is related to genetic predisposition, most notably patatin-like phospholipase domain-containing 33 G allele polymorphism that leads to intrahepatic triglyceride accumulation and insulin resistance. Nonobese NAFLD is associated with components of metabolic syndrome and, especially, visceral obesity which seems to be an important etiological factor in this group. Dietary factors and, specifically, a high fructose diet seem to play a role. Cardiovascular events remain the main cause of mortality and morbidity in NAFLD, including in the nonobese population. There is not enough data regarding treatment in non-obese NAFLD patients, but similar to NAFLD in obese subjects, lifestyle changes that include dietary modification, physical activity, and weight loss remain the mainstay of treatment.

Gastric cancer in Africa:Current management and outcomes

Gastric cancer is the fourth most common cancer and second most common cause of cancer death worldwide.Globally,gastric cancer poses a significant public health burden-both economically and socially.In 2008,the economic burden from premature cancer deaths and disability was$895 billion and gastric cancer was the second highest cancer responsible for healthy life lost.With the expected increase in cancer deaths and non-communicable diseases,these costs are expected to rise and impact patient care.World Health Organization,estimates a 15%increase in non-communicable disease worldwide,with more than 20%increase occurring in Africa between 2010 and 2020.Mali,West Africa,is ranked 15th highest incidence of gastric cancer worldwide at a rate of 20.3/100000,yet very scarce published data evaluating etiology,prevention or management exist.It is understood that risk factors of gastric cancer are multifactorial and include infectious agents(Helicobacter pylori,Epstein-Barr virus),genetic,dietary,and environmental factors(alcohol,smoking).Interestingly,African patients with gastric cancer are younger,in their 3rd-4th decade,and present at a late stage of the disease.There is sparse data regarding gastric cancer in Africa due to lack of data collection and under-reporting,which impacts incidence and mortality rates.Currently,GLOBOCAN,an International Agency for Research on Cancer resource,is the most comprehensive available resource allowing comparison between nations.In resource limited settings,with already restricted healthcare funding,data is needed to establish programs in Africa that increase gastric cancer awareness,curtail the economic burden,and improve patient management and survival outcomes.