Endoscopic submucosal dissection for early gastric cancer with undifferentiated-type histology:A meta-analysis

AIM: To evaluate the efficacy and safety of endoscopicsubmucosal dissection(ESD) for early gastric cancer(EGC) with undifferentiated-type histology.METHODS: A systematic literature review was conducted using the core databases. Complete resection,curative resection, en bloc resection, recurrence and adverse event rate were extracted and analyzed. A random effect model was applied. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated using a funnel plot, the trim and fill method, Egger's test,and a rank correlation test.RESULTS: Fourteen retrospective studies between2009 and 2014 were identified(972 EGC lesions with undifferentiated-type histology). The total en bloc and complete resection rates were estimated as92.1%(95%CI: 87.4%-95.2%) and 77.5%(95%CI:69.3%-84%), respectively. The total curative resection rate was 61.4%(95%CI: 44.5%-75.9%). The overall recurrence rate was 7.6%(95%CI: 3.4%-16%).Limited to histologically diagnosed expanded-criteria lesions, the en bloc and complete resection rates were91.2% and 85.6%, respectively. The curative resection rate was 79.8%.CONCLUSION: In this analysis, ESD is a technically feasible treatment modality for EGC with undifferentiatedtype histology. Long-term studies are needed to confirm these therapeutic outcomes.

Two-year delay in ulcerative colitis diagnosis is associated with anti-tumor necrosis factor alpha use

BACKGROUND Ulcerative colitis(UC)is an uncommon inflammatory bowel disease(IBD).However,its incidence has recently increased in South Korea.Moreover,UC diagnoses are frequently delayed,and the relationship between diagnostic delay and UC prognosis has not been extensively studied in South Korean patients.AIM To identify meaningful diagnostic delay affecting UC prognosis and to evaluate risk factors associated with diagnostic delay in South Korean patients.METHODS Medical records of 718 patients with UC who visited the outpatient clinic of six university hospitals in South Korea were reviewed;167 cases were excluded because the first symptom date was unknown.We evaluated the relationship between the prognosis and a diagnostic delay of 3,6,12,18,and 24 mo by comparing the prognostic factors[anti-tumor necrosis factor(TNF)-αuse,admission history due to acute flare-ups,frequent admission due to flare-ups,surgery associated with UC,and the clinical remission state at the latest followup]at each diagnostic interval.RESULTS The mean diagnostic interval was 223.3±483.2 d(median,69 d;75th percentile,195 d).Among the prognostic factors,anti-TNFαuse was significantly increased after a diagnostic delay of 24 mo.Clinical risk factors predictive of a 24-mo diagnostic delay were age<60 years at diagnosis[odd ratio(OR)=14.778,95%confidence interval(CI):1.731-126.121],smoking history(OR=2.688,95%CI:1.239-5.747,P=0.012),and misdiagnosis of hemorrhoids(OR=11.066,95%CI:3.596-34.053).Anti-TNFαuse was associated with extensive UC at diagnosis(OR=3.768,95%CI:1.860-7.632)and 24-mo diagnostic delay(OR=2.599,95%CI:1.006-4.916).CONCLUSION A diagnostic delay>24 mo was associated with increased anti-TNFαuse.Age<60 years at diagnosis,smoking history,and misdiagnosis of hemorrhoids were risk factors for delayed diagnosis.

Trends in the eradication rates of Helicobacter pylori infection for eleven years

AIM:To evaluate the trends in the eradication rate of Helicobacter pylori(H.pylori) over the past 11 years in a single center.METHODS:This retrospective study covered the period from January 2000 to December 2010.We evaluated 5746 patients diagnosed with gastric ulcers(GU),duodenal ulcers(DU),GU + DU,or nonpeptic ulcers associated with an H.pylori infection.We treated them annually with the 2 wk standard first-line triple regimen,proton pump inhibitor(PPI) + amoxicilin + clarithromycin(PAC;PPI,clarithromycin 500 mg,and amoxicillin 1 g,all twice a day).The follow-up test was performed at least 4 wk after the completion of the 2 wk standard H.pylori eradication using the PAC regimen.We also assessed the eradication rates of 1 wk second-line therapy with a quadruple standard regimen(PPI b.i.d.,tripotassium dicitrate bismuthate 300 mg q.i.d.,metronidazole 500 mg t.i.d.,and tetracycline 500 mg q.i.d.) after the failure of the first-line therapy.Statistical analysis was performed with 95%CI for the differences in the annual eradication rates.RESULTS:A total of 5746 patients [2333 males(58.8%),1636 females(41.2%);mean age of males vs females 51.31 ± 13.1 years vs 52.76 ± 13.6 years,P < 0.05,total mean age 51.9 ± 13.3 years(mean ± SD)] were investigated.Among these patients,1674 patients were excluded:35 patients refused treatment;18 patients ceased H.pylori eradication due to side effects;1211 patients had inappropriate indications for H.pylori eradication,having undergone stomach cancer operation or chemotherapy;and 410 patients did not undergo the follow-up.We also excluded 103 patients who wanted to stop eradication treatment after only 1 wk due to poor compliance or the side effects mentioned above.Finally,we evaluated the annual eradication success rates in a total of 3969 patients who received 2 wk first-line PAC therapy.The endoscopic and clinical findings in patients who received the 2 wk PAC were as follows:gastric ulcer in 855(21.5%);duodenal ulcer in 878(22.1%);gastric and duodenal ulcer in 124(3.1%),erosive,atrophic gastritis and functional dyspepsia in 2055(51.8%);and other findings(e.g.,MALToma,patients who wanted to receive the therapy even though they had no abnormal endoscopic finding) in 57(0.5%).The overall eradication rate of the 2 wk standard firstline triple regimen was 86.5%.The annual eradication rates from 2000 to 2010 were 86.7%,85.4%,86.5%,83.3%,89.9%,90.5%,88.4%,84.5%,89.1%,85.8%,and 88.3%,sequentially(P = 0.06).No definite evidence of a significant change in the eradication rate was seen during the past eleven years.The eradication rates of second-line therapy were 88.9%,82.4%,85%,83.9%,77.3%,85.7%,84.4%,87.3%,83.3%,88.9%,and 84%(P = 0.77).The overall eradication rate of 1 wk quadruple second-line therapy was 84.7%.There was no significant difference in the eradication rate according to the H.pylori associated diseases.CONCLUSION:This study showed that there was no trend change in the H.pylori eradication rate over the most recent 11 years in our institution.

Pravastatin activates PPARα/PPARγexpression in the liver and gallbladder epithelium of hamsters

BACKGROUND:Our earlier study with cultured gallbladder epithelial cells demonstrated that statins(HMG-CoA reductase inhibitors)activate the expression of PPARαand PPARγ, consequently blocking the production of pro-inflmmatory cytokines.The present study used hamsters to investigate the effects of pavastatin on PPARα/PPARγexpression in the liver and gallbladder epithelium,and to determine whether pravastatin suppresses cholesterol crystal formation in the gallbladder. METHODS:A total of 40 Golden Syrian male hamsters(4 weeks old)were randomly assigned to four groups(basal diet control; basal diet+pavastatin;high cholesterol diet;high cholesterol diet+pravastatin).All hamsters were 11 weeks old at the end of the experiment.The liver,gallbladder and bile were harvested. Immunohistochemical staining and Western blotting for PPARαand PPARγwere performed in the liver and gallbladder. A drop of fresh bile was examined for cholesterol crystals under a microscope. RESULTS:In the gallbladder and liver of the hamsters, pravastatin activated the PPARαand PPARγexpression of gallbladder epithelial cells and hepatocytes,and particularly the response of PPARγwas much stronger than that of PPARα. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder. CONCLUSION:Pravastatin is an effective medication to activate PPARs(especially PPARγ)in the liver and the gallbladder epithelium of hamsters,and contributes to the prevention of gallstone formation.

Pravastatin activates the expression of farnesoid X receptor and liver X receptor alpha in Hep3B cells

BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among the nuclear hormone receptors that regulate cholesterol-bile acid metabolism in the nuclei of hepatocytes. However, there is controversy over whether or how statins change the expression of peroxisome proliferator-activated receptor(PPAR)α, PPARγ, liver X receptor α(LXRα), farnesoid X receptor(FXR), ABCG5, ABCG8, and 7α-hydroxylase(CYP7A1) which are directly involved in the cholesterol saturation index in bile. METHODS: Human Hep3B cells were cultured on dishes. MTT assays were performed to determine the appropriate concentrations of reagents to be used. The protein expression of PPARα and PPARγ was measured by Western blotting analysis, and the mRNA expression of LXRα, FXR, ABCG5, ABCG8 and CYP7A1 was estimated by RT-PCR. RESULTS: In cultured Hep3B cells, pravastatin activated PPARα and PPARγ protein expression, induced stronger expression of PPARγ than that of PPARα, increased LXRα mRNA expression, activated ABCG5 and ABCG8 mRNA expression mediated by FXR as well as LXRα, enhanced FXR mRNA expression, and increased CYP7A1 mRNA expression mediated by the PPARγ and LXRα pathways, together or independently. CONCLUSION: Our data suggested that pravastatin prevents cholesterol gallstone diseases via the increase of FXR, LXRαand CYP7A1 in human hepatocytes.