Helicobacter pylori Eradication Can Reverse the Methylation-Associated Regulation of miR-200a/b in Gastric Carcinogenesis

Background/Aims@#Epigenetic change is one of the mecha-nisms that regulates the expression of microRNAs (miRNAs) and is known to play a role in Helicobacter pylori-associated gastric carcinogenesis. We aimed to evaluate the epigen-etic changes ofmiR-200a/b in H. pylori-associated gastric carcinogenesis and restoration after eradication. @*Methods@#The expression and methylation levels of miR-200a/b were evaluated in gastric cancer (GC) cell lines, human gastric mu-cosa of H. pylori-negative and -positive controls, and H. pyloripositive GC patients. Next, the changes in the expression and methylation levels of miR-200a/b were compared between H. pylori-eradication and H. pylori-persistence groups at 6 months. Real-time reverse transcription-polymerase chain reaction was conducted to investigate the miRNA expression levels, and MethyLight was performed to assess the meth-ylation levels. @*Results@#In the GC cell lines, the level ofmiR-200a/b methylation decreased and the level of expression increased after demethylation. In the human gastric mucosa, the miR-200a/b methylation levels increased in the following group order: H. pylori-negative control group, H. pylori-positive control group, and H. pylori-positive GC group. Conversely, the miR-200a/b expression levels decreased in the same order.In the H. pylori-persistence group, no significant changes were observed in the methylation and expression levels of miR-200a/b after 6 months, whereas the level of methyla-tion decreased and the level of expression of miR-200a/b increased significantly 6 months in the H. pylori-eradication group. @*Conclusions@#Epigenetic alterations ofmiR-200a/bmay be implicated in H. pylori-induced gastric carcinogen-esis. This field defect for cancerization is suggested to be improved by H. pylori eradication.

Clinical features and outcomes in spontaneous intramural small bowel hematoma: cohort study and literature review

BACKGROUND/AIMS: Spontaneous intramural small bowel hematoma (SISBH) is an extremely rare complication of anticoagulant or antiplatelet therapy. We assessed the clinical characteristics and outcomes of patients with SISBH according to the anatomical location of the hematoma. METHODS: From January 2003 to February 2016, medical records for all patients hospitalized for SISBH at 2 tertiary referral hospitals were retrospectively reviewed. The primary outcome was requirement for surgery. RESULTS: A total of 37 patients were enrolled. The mean age was 74.1 years. Among them, 33 patients (89.2%) were taking anticoagulant and/or antiplatelet agents. Duodenal intramural hematoma was detected in 4 patients (10.8%), jejunal in 16 (43.2%), and ileal in 17 (45.9%). Compared to jejunal and ileal involvement, duodenal intramural hematoma was significantly associated with high Charlson comorbidity index and low levels of white blood cells, hemoglobin, and platelets in the blood. SISBH in the duodenum was related to thrombocytopenia in 3 patients following systemic chemotherapy for malignancy. All patients with SISBH showed clinical improvement with conservative therapy. Mean length of hospital stay was 9.35 days. Independent predictors of a hospital stay of more than 7 days were body weight less than 60 kg (odds ratio [OR], 12.213; 95% confidence interval [CI], 1.755–84.998; P=0.011) and a history of cerebrovascular accidents (OR, 6.667; 95% CI, 1.121–39.650; P=0.037). CONCLUSIONS: Compared to jejunal and ileal involvement, thrombocytopenia may result in spontaneous duodenal intramural hematoma among patients who are treated with systemic chemotherapy for malignancies. Patients with SISBH have excellent clinical outcomes with conservative therapy regardless of the anatomical location of the hematoma.

Continuous Use of Thienopyridine May Be as Safe as Low-Dose Aspirin in Endoscopic Resection of Gastric Tumors

BACKGROUND/AIMS: Current guidelines recommend withholding antiplatelets for 5–7 days before high-risk endoscopic procedures. We investigated whether this reduces post-endoscopic submucosal dissection (ESD) bleeding. METHODS: Gastric ESD cases with antiplatelets were retorospectively reviewed. Withholding antiplatelets for 5–7 days before ESD was defined as cessation and 0–4 days as continuation. The rate and risk of post-ESD bleeding according to the types and cessation of antiplatelets were assessed. RESULTS: Among the 215 patients (117 adenoma and 98 early gastric cancer), 161 patients were on single (94 aspirin, 56 thienopyridine, and 11 other agents), 51 on dual, and 3 on triple antiplatelets. Post-ESD bleeding rates were 12.8% in aspirin users, 3.6% in thienopyridine, 27.5% in dual, 33.3% in triple therapy, and 9.7% in the cessation and 15.0% in the continuation group. Multiple antiplatelets (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.01 to 5.76) and specimen size ≥ 5.5 cm (OR, 2.84; 95% CI, 1.04 to 7.73) were the risk of bleeding, while continuation of thienopyridine (OR, 0.23; 95% CI, 0.05 to 1.09) and antiplatelets (OR, 1.83; 95% CI, 0.68 to 4.94) did not increase the risk of bleeding. CONCLUSIONS: Continuing thienopyridine and aspirin did not increase the risk of post-ESD. Multiple antiplatelet therapy and a large specimen size were independent risk factors of post-ESD bleeding.

Comparison of Tight Junction Protein-Related Gene mRNA Expression Levels between Male and Female Gastroesophageal Reflux Disease Patients

BACKGROUND/AIMS: Male predominance has been observed in the erosive reflux disease (ERD), but reverse finding in nonerosive reflux disease (NERD). This suggests sex-specific medicine approach is needed but its mechanism is remained to be elucidated. We aimed to compare clinical characteristics and mRNA expression levels of tight junction-related proteins between male and female gastroesophageal reflux disease (GERD). METHODS: Sixteen healthy controls, 45 ERD, and 14 NERD patients received upper endoscopies and completed questionnaires. Quantitative real-time polymerase chain reactions of occludin (OCLN), zonal occludens (ZO) 1, claudin-1 (CLDN1) and claudin-4 (CLDN4), and neurokinin 1 receptor (NK1R) were performed in the distal esophageal mucosal specimen. These results were analyzed by sex. RESULTS: Female GERD patients were affected more by reflux symptoms than males. The impairment of overall quality of life was more prominent in female patients with reflux symptoms than male patients (5.6±0.2 vs 4.9±0.6, p=0.009). The levels of OCLN mRNA expression were significantly lower in the male ERD group. On the other hand, those of CLDN1, CLDN4, and NK1R except ZO-1 were significantly higher in the male ERD group. CONCLUSIONS: We demonstrated that female ERD/NERD patients were affected more by GERD and male ERD patients showed significant changes of tight junction protein mRNA expression levels.

Helicobacter pylori Is Associated with miR-133a Expression through Promoter Methylation in Gastric Carcinogenesis

BACKGROUND/AIMS: To investigate whether Helicobacter pylori eradication can reverse epigenetic silencing of microRNAs (miRNAs) which are associated with H. pylori-induced gastric carcinogenesis. METHODS: We examined expression and promoter methylation of miR-34b/c, miR-133a, let-7a, and let-7i in gastric cancer cell line, before/after demethylation. Among them, epigenetically controlled miRNAs were identified. Their expression and promoter methylation was examined in human tissues of H. pylori-positive gastric cancer (T), H. pylori-positive gastritis (H), and H. pylori-negative controls (C). We also compared changes of miRNA expression and promoter methylation in H. pylori-positive patients who were endoscopically treated for early gastric cancer, between baseline and 1 year later according to eradication status. RESULTS: In gastric cancer cell line, miR-34b/c and miR-133a showed epigenetic silencing. In human tissues, miR-34b/c and miR-133a showed serial increase of promoter methylation in order of C, H, and T (all, p < 0.01), and the miR-133a expression showed serial decrease (C vs H, p=0.02; H vs T, p=0.01; C vs T, p < 0.01) while miR-34b and miR-34c expressions did not. H. pylori eradication induced decrease of methylation (p < 0.01) and increase of miR-133a expression (p=0.03), compared with noneradication group. CONCLUSIONS: This result suggests H. pylori eradication could reverse methylation-silencing of miR-133a which is involved in H. pylori-induced gastric carcinogenesis.

Long-Term Effects of Helicobacter pylori Eradication on Metachronous Gastric Cancer Development

BACKGROUND/AIMS: Gastric mucosal atrophy and intestinal metaplasia due to Helicobacter pylori infection are the main precursor lesions of gastric cancer. The aim of this study was to evaluate the long-term effects of H. pylori eradication on the progression of precancerous lesions to metachronous cancer after endoscopic resection of early gastric cancer (EGC). METHODS: Patients who underwent endoscopic resection of EGC were retrospectively reviewed. Changes in precancerous lesions and development of metachronous cancer were compared according to H. pylori eradication and final infection status. RESULTS: In total, 565 patients were followed for over 5 years after endoscopic resection of EGC. The grade of atrophy on corpus was significantly lower in the H. pylori-eradicated group than in the persistent group during follow-up (p=0.029). In patients < 70 years of age, the cumulative incidence rate of metachronous cancer was significantly lower in the H. pylori-eradicated group than in the persistent group (p=0.018). Age was an independent risk factor for metachronous cancer development. CONCLUSIONS: H. pylori eradication might prevent the development of metachronous cancer in patients < 70 years of age by delaying the progression of precancerous lesions after endoscopic resection of EGC.

Clinical Implication and Risk Factors for Malignancy of Atypical Gastric Gland during Forceps Biopsy

BACKGROUND/AIMS: Although forceps biopsy is performed for suspicious gastric tumors during endoscopy, it is difficult to determine treatment strategies for atypical gastric glands due to uncertainty of the diagnosis. The aim of this study was to investigate clinical implications and risk factors for predicting malignancy in atypical gastric glands during forceps biopsy. METHODS: We retrospectively reviewed medical records of 252 patients with a diagnosis of atypical gastric gland during forceps biopsy. Predictors of malignancy were analyzed using initial endoscopic findings and clinical data. RESULTS: The final diagnosis for 252 consecutive patients was gastric cancer in 189 (75%), adenoma in 26 (10.3%), and gastritis in 37 (14.7%). In the multivariate analysis, lesion sizes of more than 10 mm (odds ratio [OR], 3.021; 95% confidence interval [CI], 1.480 to 6.165; p=0.002), depressed morphology (OR, 3.181; 95% CI, 1.579 to 6.406, p=0.001), and surface nodularity (OR, 3.432; 95% CI, 1.667 to 7.064, p=0.001) were significant risk factors for malignancy. CONCLUSIONS: Further evaluation and treatment should be considered for atypical gastric gland during forceps biopsy if there is a large-sized (>10 mm) lesion, depressed morphology, or surface nodularity.

Comparisons of Gut Microbiota Among Healthy Control, Patients With Conventional Adenoma, Sessile Serrated Adenoma, and Colorectal Cancer

BACKGROUND: Studies on gut microbiota regarding colorectal carcinogenesis, including sessile serrated adenoma (SSA), have been scarce. The aim of this study is to investigate the role of mucosa-associated gut microbiota in the colorectal carcinogenesis. METHODS: We collected biopsy samples of normal rectal mucosa during colonoscopy from healthy control and patients with conventional adenoma, SSA, and colorectal cancer (CRC), respectively (n = 6). Pyrosequencing for 16S rRNA gene of bacteria was performed to compare gut microbiota. RESULTS: The most abundant phylum in total samples was Proteobacteria (55.6%), followed by Firmicutes (27.4%) and Bacteroidetes (11.6%). There was no significant difference in relative abundance of the phylum level among the four groups. Fusobacterium nucleatum, known to be frequently detected during colorectal carcinogenesis, was found in only one sample of patient with SSA. The rarefaction curves showed that the diversity of mucosal communities of patients with CRC is the lowest among the four groups and the diversity of mucosal communities of patients with SSA is higher than that of healthy control. Among the four groups, Shannon's and Simpson's index for diversity was the lowest and the highest in the patients with CRC, respectively; it did not reach statistical significance. The proportion of genus Pseudomonas was very high in the samples of patients with stage II–IV CRC compared with those with stage I CRC (59.3% vs. 0.3%, P = 0.064). CONCLUSIONS: Our study suggests no significant role of mucosa-associated gut microbiota in the colorectal carcinogenesis. Further study for many samples or using fecal material could be helpful.

Balloon Expulsion Test Does Not Seem to Be Useful for Screening or Exclusion of Dyssynergic Defecation as a Single Test

BACKGROUND/AIMS: Balloon expulsion test (BET) is regarded as a screening tool of dyssynergic defecation (DD). However, some patients with normal BET results may be treated effectively by biofeedback training. This study aims to validate BET as a single screening test. METHODS: Two hundred and thirty-two patients who were diagnosed with functional constipation or irritable bowel syndrome with constipation who underwent anorectal manometry (ARM) and BET at Seoul National University Hospital were enrolled. We evaluated the validity of BET based on ARM and electromyography (EMG) during biofeedback training. RESULTS: If BET ≤ 1 minute was defined as normal, sensitivity and negative predictive value (NPV) of BET in predicting paradoxical contraction based on ARM findings were 71.4% and 13.9%. If BET ≤ 3 minutes was defined as normal, sensitivity and NPV were 35.2% and 6.6%. Specificity and positive predictive value (PPV) of BET ≤ 3 minutes criteria were 84.8% and 93.3%. Same analysis was conducted in 107 patients who underwent EMG during biofeedback training. With 1-minute criteria, sensitivity and NPV of BET were 70.3% and 14.3%. With 3 minutes criteria, sensitivity and NPV of BET was 38.6% and 8.8%. Specificity and positive predictive values were both 100.0%. CONCLUSIONS: Based on either ARM or EMG during biofeedback training, sensitivity was at most 71.4% and NPV was less than 15.0% irrespective of whether BET was within 1minute or within 3 minutes. BET seems to have a limitation as both a screening test for dyssynergic defecation and a simple assessment to rule out the necessity of biofeedback training.

Pantoprazole Does Not Reduce the Antiplatelet Effect of Clopidogrel: A Randomized Controlled Trial in Korea

BACKGROUND/AIMS: Concerns that proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel could hamper the appropriate prescription of PPIs. We evaluated the influence of pantoprazole on the antiplatelet effect of clopidogrel compared with ranitidine, which is regarded as safe, after stratification of the population according to the presence of a cytochrome (CYP) 2C19 polymorphism in Korea. METHODS: Forty patients who underwent dual antiplatelet therapy were randomized to receive pantoprazole (n=20) or ranitidine (n=20). Platelet aggregation was evaluated by impedance aggregometry at baseline (D0) and 8 days after acid-lowering treatments (D9). CYP2C19 was genotyped by polymerase chain reaction restriction fragment length polymorphism. RESULTS: After co-treatment, the percentage of clopidogrel low-response was 11.1% (2/18) in the pantoprazole group and 10.5% (2/19) in the ranitidine group (p=0.954). The impedance values with adenosine diphosphate stimulus after acid-lowering treatments did not significantly differ between the two groups. In a multiple regression analysis, only ST-elevation myocardial infarction was marginally associated with a reduced antiplatelet effect (odds ratio, 12.07; 95% confidence interval, 0.84 to 173.78). However, pantoprazole use did not affect the antiplatelet effect after correction for the CYP2C19 polymorphism. CONCLUSIONS: This study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).

Helicobacter pylori Eradication Downregulates Cellular Inhibitor of Apoptosis Protein 2 in Gastric Carcinogenesis

BACKGROUND/AIMS: To evaluate the expression of cellular inhibitor of apoptosis protein 2 (cIAP2) during gastric carcinogenesis after Helicobacter pylori (HP) infection and after HP eradication. METHODS: We divided non-cancer patients into four groups according to the status of HP infection and atrophic gastritis (AG)/intestinal metaplasia (IM). We compared cIAP2 mRNA expression among these four groups and patients with HP-positive early gastric cancer (EGC) by using real-time polymerase chain reaction (PCR). We evaluated the expression of cIAP2 messenger RNA (mRNA)/protein by using real-time PCR/immunohistochemistry and the degree of apoptosis with a terminal deoxynucleotidyl transferase-mediated nick end labeling assay before and 12 months after endoscopic submucosal dissection (ESD) in HP-positive EGC patients, regardless of whether they had undergone eradication therapy. RESULTS: The expression of cIAP2 mRNA was significantly higher in the groups with HP(+), AG/IM(+), and HP-positive EGC than in the control, HP(+), and AG/IM(−) groups (p<0.005). In the HP eradication group, the expression of cIAP2 mRNA/protein significantly decreased (p=0.006) and apoptosis increased at the 12-month follow-up after ESD. In the HP noneradication group, the aforementioned changes were not found during the same follow-up period. CONCLUSIONS: The expression of cIAP2 increased during gastric carcinogenesis after HP infection; HP eradication in the patients who had undergone ESD for EGC reversed overexpression of cIAP2 and suppressed cell apoptosis.

Risk Factors for Metachronous Gastric Neoplasms in Patients Who Underwent Endoscopic Resection of a Gastric Neoplasm

BACKGROUND/AIMS: To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm. METHODS: We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms. RESULTS: A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 high-grade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020). CONCLUSIONS: In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms.

Comparison of the Efficacies of Parenteral Iron Sucrose and Oral Iron Sulfate for Anemic Patients with Inflammatory Bowel Disease in Korea

BACKGROUND/AIMS: The optimal route for iron administration in anemic patients with inflammatory bowel disease (IBD) has not been determined. The aim of this study was to compare the efficacies of parenteral and oral iron therapy in IBD patients in Korea. METHODS: A retrospective multicenter study was performed. Patients who had been administered parenteral iron were matched to the controls with oral iron at a 1:1 ratio according to age, sex, and type of IBD. RESULTS: Patients that received parenteral iron exhibited increases in hemoglobin levels of ≥20% from the baseline at lower doses and in shorter durations (p=0.034 and p=0.046, respectively). In the multivariate analysis, parenteral iron therapy appeared to be more efficient than oral iron therapy, but this difference was not statistically significant (hazard ratio [HR], 1.552; 95% confidence interval [CI], 0.844 to 2.851; p=0.157). Patients with ulcerative colitis responded better to iron therapy than those with Crohn's disease (HR, 3.415; 95% CI, 1.808 to 6.450; p<0.001). Patients with an initial hemoglobin level of 10 g/dL or higher responded poorly to iron therapy (HR, 0.345; 95% CI, 0.177 to 0.671; p=0.002). CONCLUSIONS: Parenteral iron therapy appears to be more efficient than oral iron therapy. Physicians should focus on the iron deficiency of IBD patients and consider parenteral iron supplements in appropriate patient groups.

Comparison of Gastric Microbiota Between Gastric Juice and Mucosa by Next Generation Sequencing Method

BACKGROUND: Not much is known about the role of gastric microbiota except for Helicobacter pylori in human health and disease. In this study, we aimed to detect human gastric microbiota in both gastric mucosa and gastric juice by barcoded 454-pyrosequencing of the 16S rRNA gene and to compare the results from mucosa and juice. METHODS: Gastric biopsies and stomach juices were collected from 4 subjects who underwent standard endoscopy at Seoul National University Bundang Hospital. Gastric microbiota of antral mucosa, corpus mucosa samples, and gastric fluids were analyzed by barcoded 454-pyrosequencing of the 16S rRNA gene. The analysis focused on bacteria, such as H. pylori and nitrosating or nitrate-reducing bacteria. RESULTS: Gastric fluid samples showed higher diversity compared to that of gastric mucosa samples. The mean of operational taxonomic units was higher in gastric fluid than in gastric mucosa. The samples of gastric fluid and gastric mucosa showed different composition of phyla. The composition of H. pylori and Proteobacteria was higher in mucosa samples compared to gastric fluid samples (H. pylori, 66.5% vs. 3.3%, P = 0.033; Proteobacteria, 75.4% vs. 26.3%, P = 0.041), while Actinobacteria, Bacteroidetes, and Firmicutes were proportioned relatively less in mucosa samples than gastric fluid. However there was no significant difference. (Actinobacteria, 3.5% vs. 20.2%, P = 0.312; Bacteroidetes, 6.0% vs. 14.8%, P = 0.329; Firmicutes, 12.8% vs. 33.4%, P = 0.246). CONCLUSIONS: Even though these samples were small, gastric mucosa could be more effective than gastric fluid in the detection of meaningful gastric microbiota by pyrosequencing.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study

BACKGROUND/AIMS: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. METHODS: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). RESULTS: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole-treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. CONCLUSIONS: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

Impact of Long-Term Proton Pump Inhibitor Therapy on Gut Microbiota in F344 Rats: Pilot Study

BACKGROUND/AIMS: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. METHODS: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). RESULTS: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole-treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. CONCLUSIONS: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum.

A Case of Hepatocellular Carcinoma in a Patient with Crohn's Disease / 대한내과학회지

Hepatocellular carcinomas (HCCs) in patients with Crohn's disease (CD) without underlying chronic hepatitis or liver cirrhosis are extremely rare. Previously reported cases occurred in patients who had developed CD at a young age and had been treated with immunosuppressive agents long-term. We herein report the first case of HCC in a 34-year-old patient with CD in Korea. The patient was treated with azathioprine for 14 years and had undergone repeated surgeries for CD. During the follow-up period, the patient was hospitalized for colon perforation and pericolic abscess formation. Computed tomography showed a liver mass, and HCC was diagnosed based on liver biopsy. The patient underwent right hemicolectomy for colon perforation and transcatheter arterial chemoembolization followed by radiofrequency ablation for the HCC. The present case is similar to previously reported cases with the exception of the liver pathology findings, which exhibited neither primary sclerosing cholangitis nor focal hepatic glycogenolysis.

A Randomized Controlled Clinical Study Comparing the Diagnostic Accuracy of the Histologic Prediction for Colorectal Polyps Depending on the Use of Either Magnified or Nonmagnified Narrow Band Imaging

BACKGROUND/AIMS: The aim of this study was to compare the diagnostic capabilities of narrow band imaging (NBI) colonoscopy with and without optical magnification in differentiating neoplastic from nonneoplastic colorectal polyps. METHODS: Between April 2012 and March 2013, 122 patients with colorectal polyps detected by using diagnostic conventional colonoscopy were prospectively enrolled. A total of 236 polyps were evaluated with NBI, in vivo in real time during therapeutic colonoscopy, by one experienced endoscopist. Whether magnification was used or not was determined by randomization. After an in vivo real-time endoscopic prediction of histology, all lesions were endoscopically excised. Surgical pathologic reports were used as the criterion standards. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of identifying neoplastic polyps were calculated. RESULTS: A total of 236 lesions with an average size of 5.6 mm in 122 patients were assessed (159 neoplastic, 77 nonneoplastic). The Sn, Sp, PPV, and NPV in differentiating neoplastic from nonneoplastic lesions with the magnified NBI were 97.5%, 83.3%, 94.0%, and 92.6%, respectively, whereas those of the nonmagnified NBI group were 97.5%, 85.1%, 91.7%, and 95.2%, respectively. CONCLUSIONS: Nonmagnified NBI colonoscopy distinguishes neoplastic from nonneoplastic colorectal polyps as accurately as does magnified NBI colonoscopy.

Usefulness of the Cytomegalovirus Antigenemia Assay in Patients With Ulcerative Colitis

BACKGROUND/AIMS: Patients with ulcerative colitis (UC) are at high risk for cytomegalovirus (CMV) reactivation. The usefulness of the CMV antigenemia assay in active UC patients has rarely been studied. We assessed whether the assay detects CMV colitis and predicts clinical outcomes in patients with UC. METHODS: We retrospectively reviewed the medical records of patients hospitalized for moderate-to-severe UC from 2003 to 2012. Positive CMV antigenemia was defined as > or =1 pp65-positive cell per 2x10(5) polymorphonuclear neutrophils. CMV colitis was defined as the presence of inclusion bodies and/or positive immunohistochemistry in the colonic mucosa. The primary outcome was steroid refractoriness, defined as the absence of clinical improvement after intravenous high-dose steroid administration. RESULTS: A total of 43 patients were enrolled. CMV antigenemia was detected in 12 (27.9%) patients. Positive CMV antigenemia was significantly associated with CMV colitis (P =0.001). The sensitivity and specificity of positive CMV antigenemia for diagnosing CMV colitis were 66.7% and 87.1%, respectively. Steroid refractoriness was found in 11 of 12 (91.7%) and 12 of 31 (38.7%) patients with positive and negative CMV antigenemia, respectively (P =0.002). The independent predictors for steroid refractoriness were positive CMV antigenemia (adjusted odds ratio [OR], 7.73; 95% confidence interval [CI], 1.22-49.19; P =0.030) and a shorter duration from the diagnosis of UC (adjusted OR, 0.99; 95% CI, 0.98-0.99; P =0.025). CONCLUSIONS: The CMV antigenemia assay shows low sensitivity but high specificity for detecting CMV colitis and may predict steroid-refractory UC. Early rescue therapy might be considered in UC patients positive for CMV antigenemia.

Long-term Outcomes and Risk Factors for Reoperation After Surgical Treatment for Gastrointestinal Crohn Disease According to Anti-tumor Necrosis Factor-alpha Antibody Use: 35 Years of Experience at a Single Institute in Korea

PURPOSE: Crohn disease is characterized by high rates of recurrence and reoperations. However, few studies have investigated long-term surgical outcomes in Asian populations. We investigated risk factors for reoperation, particularly those associated with anti-tumor necrosis factor-alpha (anti-TNF-alpha) antibody use, and long-term follow-up results. METHODS: We reviewed the records of 148 patients (100 males and 48 females) who underwent surgery for gastrointestinal Crohn disease and retrospectively analyzed long-term outcomes and risk factors. RESULTS: The mean age at diagnosis was 28.8 years. Thirty-eight patients (25.7%) received monoclonal antibody treatment before reoperation. A small bowel and colon resection was most commonly performed (83 patients, 56.1%). The median follow-up was 149 months, during which 47 patients underwent reoperation. The median interval between the primary and the secondary surgeries was 65 months, with accumulated reoperation rates of 16.5%, 31.8%, and 57.2% after 5, 10, and 15 years, respectively. Obstruction was the most common indication for reoperation (37 patients, 25.0%). In a multivariable analysis, age <17 years at diagnosis (A1) (odds ratio [OR], 2.20; P = 0.023), penetrating behavior (B3) (OR, 4.39; P < 0.001), and no azathioprine use (OR, 2.87; P = 0.003) were associated with reoperation. Anti-TNF-alpha antibody use did not affect the reoperation rate (P = 0.767). CONCLUSION: We showed a high reoperation rate regardless of treatment with anti-TNF-alpha antibody, which indicates that recurrent surgery is still needed to cure patients with gastrointestinal Crohn diseases. Younger age at primary operation, penetrating behavior, and no azathioprine use were significant factors associated with reoperation for gastrointestinal Crohn disease.