Jong-Chul Rhee

Clinical outcomes of endoscopic submucosal dissection (ESD) for treating early gastric cancer : Comparison with endoscopic mucosal resection after circumferential precutting (EMR-P)

BACKGROUNDnTo achieve en bloc resection for large lesions, endoscopic mucosal resection after circumferential precutting and endoscopic submucosal dissection techniques have been developed.nnnAIMnTo compare endoscopic submucosal dissection with endoscopic mucosal resection after circumferential precutting in terms of the clinical efficacy and safety.nnnPATIENTS AND METHODSn346 consecutive patients underwent their first endoscopic mucosal resection after circumferential precutting (103 patients) or endoscopic submucosal dissection (243 patients) for early gastric cancer and their clinical outcomes were compared.nnnRESULTSnFor early gastric cancer >or=20mm endoscopic submucosal dissection group demonstrated significantly higher en bloc resection and en bloc plus R0 resection rate compared with endoscopic mucosal resection after circumferential precutting group. For early gastric cancer with size of 10-19 mm, endoscopic submucosal dissection group also showed significantly higher en bloc resection rate. For early gastric cancer <20mm, however, en bloc plus R0 resection rate for endoscopic mucosal resection after circumferential precutting group was comparable to that for endoscopic submucosal dissection group. In case of R0 resection of intramucosal differentiated cancer, neither group showed local recurrence during the median 29 and 17 months of follow-up. Two groups did not show significant difference in the bleeding or perforation rates.nnnCONCLUSIONnFor early gastric cancer <20mm endoscopic mucosal resection after circumferential precutting may be considered as an alternative choice to endoscopic submucosal dissection. However, for early gastric cancer >or=20mm endoscopic submucosal dissection should be considered as the first choice for treating early gastric cancer.

Clinical significance of pre-S mutations in patients with genotype C hepatitis B virus infection

Summary.u2002 We investigated the overall and site‐specific prevalence of pre‐S mutations and its clinical significance in patients with genotype C hepatitis B virus (HBV) infection. Three hundred subjects were included: 50 asymptomatic carriers (AC), 87 chronic hepatitis (CH), 91 liver cirrhosis (LC) and 72 hepatocellular carcinoma (HCC). Pre‐S mutations were determined by nucleotide sequence analysis. Possible correlations between pre‐S mutations and clinical/virological parameters were examined. Pre‐S mutations were detected in 82 cases (27.3%); it was more frequently found in HCC (43.1%) and LC (35.2%) group than in the CH (20.7%) and AC (2.0%) group. Pre‐S2 deletion was the most commonly found mutation (10.7%), followed by pre‐S2 start codon mutation (9.7%), pre‐S1–S2 deletion (3.0%) and both pre‐S2 deletion and start codon mutation (2.7%). Pre‐S2 deletion and pre‐S2 start codon mutation were more frequently detected in advanced diseases (LC and HCC). Pre‐S mutations were associated with older age and higher rates of positive HBV DNA (≥0.5u2003pg/mL). Advanced disease and positive HBV DNA were shown to be independent predictors of pre‐S mutations by logistic regression analysis. These findings suggest that pre‐S mutations, especially pre‐S2 deletions and pre‐S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication.

Response rate and predictors of response in a short-term empirical trial of high-dose rabeprazole in patients with globus

Backgroundu2002 Although the aetiology of globus (the sensation of a lump in the throat) remains unclear, gastro‐oesophageal reflux disease is associated with globus. A short‐term trial with a high‐dose proton pump inhibitor has been shown to be a sensitive tool for diagnosing gastro‐oesophageal reflux disease.

How do we interpret an elevated carbohydrate antigen 19-9 level in asymptomatic subjects?

AIMnThis prospective cohort study aimed to evaluate the etiology of elevated CA 19-9 levels and to present appropriate guidelines for the asymptomatic patients.nnnMETHODSnBetween January 2004 and March 2007, we enrolled consecutive asymptomatic patients who had elevated CA 19-9 levels >37 U/mL. To evaluate the etiology, the CA 19-9 level was rechecked and further studies were carried out. If the CA 19-9 level decreased to the normal range, or if it showed a decreasing trend, then it was monitored annually. Yet, if the CA 19-9 level showed an increasing trend, then the level was monitored at intervals of 1, 3, and 6 months until no evidence of malignancy was proven.nnnRESULTSnOf the 62,976 patients, 501 (0.8%) subjects showed an elevated CA 19-9 level. This prospective analysis was conducted on 353 subjects (70.5%) who were followed up for at least 6 months. Ten patients (2.8%) were diagnosed with malignancies. There were 97 patients (27.5%) with benign diseases and 246 patients (69.7%) were deemed non-specific.nnnCONCLUSIONSnCA 19-9 should not be used as a screening tool. In the case of a persistently elevated CA 19-9 level, further work-up for determining the etiology should be done.

TP53BP2 locus is associated with gastric cancer susceptibility.

We investigated the association of the TP53BP2 locus with gastric cancer susceptibility in a Korean population. We assayed 9 single nucleotide polymorphisms (SNP) in an 82.5 kb region that included the TP53BP2 locus in 233 male gastric cancer patients and 390 unaffected healthy male controls. The allelic frequencies of 4 SNP within TP53BP2, g.206692C>T, g.198267A>T, g.164895G>A and g.152389A>T, differed significantly between cases and controls (p ≤ 0.0376). When compared to carriers of non‐risk alleles, individuals homozygotic for each of the risk alleles had a 50% increase in risk of gastric cancer (age‐adjusted odds ratio [OR] =≥ 1.48; p ≤ 0.0371). Furthermore, these 4 significantly associated SNP were in strong linkage disequilibrium (r2 ≥ 0.51). Haplotype analysis showed that individuals with the CAGA haplotype, consisting of the risk alleles at each SNP, had a 1.55‐fold higher risk for gastric cancer than individuals with the haplotype TTAT, consisting of the non‐risk alleles at each SNP (OR = 1.55; 95% confidence interval [CI] = 1.13–2.14; p = 0.00705). Two other SNP were not polymorphic in the study subjects, whereas the other 3 SNP, located toward the outside of the TP53BP2 locus, were not associated with gastric cancer susceptibility. Although the location of the pathogenic variant is not yet known, our results suggest that the TP53BP2 locus is associated with susceptibility to gastric cancer in the Korean population.

Long-term Stress and Helicobacter pylori Infection Independently Induce Gastric Mucosal Lesions in C57BL/6 Mice

Background: Long-term psychological stresses may have a role in the pathogenesis of peptic ulcer. However, the interaction between stress and Helicobacter pylori infection in the development of peptic ulcer is not established. The aim of this study was to elucidate the roles of long-term stress and H. pylori infection in the development of gastric mucosal lesions in mice. Methods: The Sydney strain (SS1) of H. pylori was inoculated into the stomach of C57BL/6 mice. Twelve weeks later, mice with or without H. pylori infection were exposed to long-term repeated water-immersion-restraint stress (WIRS) for 12 h per day, 3 times per week, for 8 weeks. Gastric mucosal lesions were evaluated both macroscopically (ulcer index) and microscopically (Updated Sydney System). Results: The long-term WIRS induced mild inflammation, oedema, interstitial haemorrhage and superficial erosions in the stomach of mice both with and without H. pylori infection. The degree of mucosal inflammation or atrophy in H. pylori -infected mice was not influenced by the stress. In the mice without H. pylori infection, the ulcer index of the stressed mice was greater than that of non-stressed mice (1.66 ± 0.39 versus 0.17 ± 0.08, P = 0.007). In the mice with H. pylori infection, the ulcer index (mean ± s x ) of the stressed mice was also greater than that of nonstressed mice (2.31 ± 0.59 versus 0.64 ± 0.22, P = 0.027). Conclusions: The present study showed that long-term stress can induce gastric mucosal inflammation and erosions, and this effect may occur independently of H. pylori infection.

Role of autonomic dysfunction in patients with functional dyspepsia

BACKGROUNDnThe role of autonomic dysfunction in patients with functional dyspepsia is not completely understood.nnnAIMSn1. to prospectively assess abnormalities of autonomic function in patients with functional dyspepsia, 2. to assess whether autonomic dysfunction in these patients is associated with a. visceral hypersensitivity or b. delayed gastric emptying or c. severity of dyspeptic symptoms.nnnPATIENTSnA series of 28 patients with functional dyspepsia and 14 healthy volunteers without gastrointestinal symptoms were studied.nnnMETHODSnAll patients and controls were submitted to a battery of five standard cardiovascular autonomic reflex tests, dyspeptic questionnaire, gastric barostat tests and gastric emptying tests.nnnRESULTSn1. Autonomic function tests showed that both sympathetic and parasympathetic scores of dyspeptic patients were significantly higher than in controls; 2. visceral hypersensitivity was confirmed in dyspeptics in response to proximal gastric distension, demonstrating lower pain threshold; 3. delayed gastric emptying occurred more frequently in patients with functional dyspepsia than in controls; 4. epigastric pain and epigastric burning were significantly more prevalent in patients with definite evidence of autonomic dysfunction; 5. No significant association was found between presence of autonomic dysfunction and presence of visceral hypersensitivity or presence of delayed gastric emptying in patients with functional dyspepsia.nnnCONCLUSIONSnWe concluded that a possible role of autonomic dysfunction in eliciting dyspeptic symptoms could not be determined from alterations in visceral hypersensitivity or delayed gastric emptying. Autonomic dysfunction might not be the major explanation for symptoms associated with functional dyspepsia.

Inhibition of cell proliferation and invasion in a human colon cancer cell line by 5-aminosalicylic acid.

BACKGROUNDn5-Aminosalicylic acid lacks the well-known side effects associated with the long-term use of non-steroidal anti-inflammatory drugs. We investigated anti-carcinogenic mechanisms of 5-aminosalicylic acid on a colon cancer cell line.nnnMETHODSnMTT analysis was performed for various colon cancer cell lines. The expression of NF-kappaB and metalloproteinases was examined in either HT-29 cells treated with IL-1beta and/or 5-aminosalicylic acid. Matrigel assay was used to evaluate invasive potential of HT-29 cells. Analysis of a cDNA microarray containing 8700 genes was performed to identify the alteration of gene expression in response to treatment to 5-aminosalicylic acid.nnnRESULTSnThe use of MTT analysis showed that 5-aminosalicylic acid suppressed the growth of HT-29 cells. The activity of NF-kappaB was also decreased by combined-treatment with IL-1beta and 5-aminosalicylic acid. The use of an ELISA and zymography demonstrated that MMP-2 and MMP-9 enzyme activity were decreased in HT-29 cells by treatment with various concentration of 5-aminosalicylic acid. A matrigel analysis demonstrated that 5-aminosalicylic acid treatment on HT-29 significantly inhibited the invasiveness of the cells. In cDNA microarray, 163 genes following 5-aminosalicylic acid exposure showed altered expression.nnnCONCLUSIONSnThis study indicated that 5-aminosalicylic acid suppresses the growth of human colon cancer cells and is able to inhibit MMPs expression via NF-kappaB mediated cell signals and invasiveness.

Methylation of p16INK4A and Mitotic Arrest Defective Protein 2 (MAD2) Genes in Gastric Marginal-Zone B-Cell Lymphomas

Background: Products of cyclin-dependent kinase inhibitor p16INK4Aand mitotic arrest defective protein 2 (MAD2) genesare key regulator proteins at the G1 restriction point and mitotic checkpoint of the cell cycle. The objective of this study was to investigate the role of promoter methylation of p16INK4A and MAD2 genes in gastric marginal-zone B-cell lymphoma (MZBCL). Materials and Methods: Gastric biopsies from 40 patients were analyzed by methylation-specific polymerase chain reaction, and the methylation status was compared with the results of BCL10 expression and t(11;18)(q21;q21) translocation. Results and Conclusion:p16INK4A was methylated in 30 of 40 MZBCLs (75%). The lymphomas with p16INK4A methylation tended to be negative for t(11;18)(q21;q21) (p = 0.011). MAD2 gene was methylated in 23 of 38 MZBCLs (61%). Lymphomas with MAD2 gene methylation more frequently expressed BCL10 (p = 0.037). These methylation profiles suggest that p16INK4A and MAD2 gene may play a role in the pathogenesis of MZBCL via different pathways; MAD2 gene is Helicobacter pylori independent with a close association with BCL10 while p16INK4A is H. pylori dependent with an inverse correlation with the t(11;18)(q21;q21) translocation.

Gastric extremely well-differentiated intestinal-type adenocarcinoma: a challenging lesion to achieve complete endoscopic resection.

Extremely well-differentiated tubular adenocarcinomas (EWDAs) of the stomach are characterized by surface maturation and their mimicking of intestinal metaplasia. Endoscopically, intramucosal EWDAs are frequently ill defined with indistinct borders due to the pallor of the neoplastic mucosa and the lack of contrast against the background atrophic and metaplastic mucosa. We evaluated the effectiveness of endoscopic resection for EWDAs after endoscopic submucosal dissection (ESD). Among 872 patients with early gastric cancer, 17 EWDAs were identified (1.9u200a%). Endoscopically, the flat or depressed type was significantly more common among EWDAs (88.2u200a%) than among early gastric cancers of other histologies (37.8u200a%; Pu200a<u200a0.01). The discrepancy between endoscopically estimated tumor size and tumor size as confirmed in pathology reports was significantly greater among EWDAs (18.4u200a±u200a22.0u200a mm) than among others (5.8u200a±u200a7.5 u200amm). Involvement of the lateral resection margin was more common (29.4u200a% vs. 2.5u200a%; Pu200a<u200a0.05), and complete resection was achieved less often in EWDAs (47.1u200a% vs. 80.4u200a%; Pu200a=u200a0.01) compared to the others. EWDAs are associated with higher rates of incomplete resection after ESD, especially along the lateral margins. Pathologists should alert endoscopists when this diagnosis is made, with its associated risks; and endoscopists should pay particular attention to the extent of these tumors during resection.