Statins and metachronous recurrence after endoscopic resection of early gastric cancer: a nationwide Korean cohort study.

BACKGROUND: Statins have shown to reduce the risk of various cancers. However, their effects on metachronous recurrence (MR) after endoscopic resection (ER) for early gastric cancer (EGC) are unknown. We evaluate their effects on MR development after ER for EGC. METHODS: We selected 11,568 patients who received ER for EGC from 2002 to 2011 from the Korean National Health Insurance database and classified into 2 groups: control and statins using propensity score matching. Metachronous recurrence was defined as the second ER or gastrectomy performed 6 months after the first ER. RESULTS: Mean follow-up period was 8.8 ± 3.1 years. Statins showed a significantly lower incidence of MR than the control group (12.5% vs 2.2%, respectively, P < 0.01). After conducting competing risk analyses and time-dependent cox regression analysis considering immortal time bias, statins still showed a lower incidence rate of MR compared to that observed in the control group. For the multivariate analysis, statins remained significant (HR 0.17; 95% CI 0.13-0.24, P < 0.01). In the dose-response analysis, an inverse dose-response relationship was identified between MR and statins (P < 0.01). CONCLUSION: Statins was significantly associated with a reduced risk of MR after ER for EGC with an inverse dose-response relationship.

Determining the current indications for endoscopic submucosal dissection in patients with Lauren mixed-type early gastric cancer.

BACKGROUND AND AIM: Recent study showed that early gastric cancer (EGC) with Lauren mixed-type (MT) histology is associated with worse prognosis. We aimed to evaluate the clinicopathologic features and prognostic significance of Lauren MT-EGCs that meets the criteria for endoscopic submucosal dissection (ESD). METHODS: We reviewed 2665 patients with EGC who underwent surgery between 2010 and 2015. The clinicopathologic features and invasiveness including lymph node metastasis (LNM) and lymphovascular invasion (LVI) of MT-EGC were compared with those of intestinal type and diffuse type by Lauren histology. RESULTS: Among 2665 patients, EGCs in 241 (9%) patients were classified as MT. Tumor size was larger and depth of invasion was greater than other histology. Among patients with MT-EGC, 16.6% (40/241) showed LNM and 22.8% (55/241) showed lymphatic invasion, which were significantly higher than that of patients with other Lauren types (8.2% and 15.3% in intestinal type and 9.1% and 8.7% in diffuse type, P < 0.001). This finding remained significant even after adjusting for depth of invasion. However, when we analyzed the patient groups who met the absolute or expanded criteria of ESD, no significant difference was observed in the rates of LNM or LVI or cancer mortality by Lauren classification. CONCLUSION: Mixed-type early gastric cancer (MT-EGC) exhibited larger tumor size, greater depth of invasion, and higher risk of LNM and LVI. However, among the patients who met the absolute or expanded criteria of ESD, no significant difference was observed in LNM, LVI, and gastric cancer mortality risk.

Exploring the possibility of endoscopic submucosal dissection for clinical submucosal invasive early gastric cancers.

BACKGROUND: The current standard treatment modality for clinical submucosal invasive (cT1b) early gastric cancer (EGC) is surgery. However, there are discrepancies in T staging between pre- and post-operative findings, and in cases of overestimation, patients may lose the opportunity to preserve the stomach. The aim of this study was to analyze surgical outcomes of cT1b EGC and determine the pre-treatment factors favoring ESD. METHODS: Patients who underwent gastrectomy for cT1b EGC with a tumor size of 30 mm or less in diameter and differentiated-type histology were retrospectively reviewed from January 2010 to December 2014. According to the final surgical pathologic results, two groups were classified: patients whose pathologic results qualified for current ESD indication (ESD-qualified group, n = 203) and patients whose pathologic results made them ineligible for ESD (ESD-disqualified group, n = 261). The preoperative clinical characteristics were compared. RESULTS: Forty-three percent of the patients (203/464) who underwent gastrectomy for cT1b EGC qualified for ESD; their endoscopic lesion tended to be smaller than 20 mm in size and located in the distal part of stomach. In addition, the ESD-qualified group showed a significantly higher proportion of well-differentiated tubular adenocarcinoma on endoscopic biopsy and of the flat/depressed type in the endoscopic evaluation. CONCLUSION: Forty-three percent of the patients with cT1b EGC who underwent gastrectomy had a chance to preserve their stomach by ESD. Therefore, pre-treatment factors such as endoscopic lesion size, location, histology, and gross type should be considered for treatment modality selection for cT1b EGC.

Novel risk stratification for metachronous recurrence after curative endoscopic submucosal dissection for early gastric cancer.

BACKGROUND AND AIMS: This study stratified the risk of developing metachronous gastric cancer (MGC) after curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) to enable customization of endoscopic surveillance for MGC. METHODS: A total of 1115 patients who underwent curative ESD based on the expanded criteria for differentiated EGC from 2005 to 2014 at a single tertiary hospital were enrolled in this retrospective cohort study. They were followed up with annual endoscopy for a median of 50.1 months. Helicobacter pylori and histologic intestinal metaplasia (IM) were evaluated. The Kaplan-Meier method and Cox regression analysis were used for risk stratification. RESULTS: Three risk groups were identified: group 1 comprised patients with a synchronous neoplasm; group 2 comprised male patients with corpus IM; and group 3 comprised male patients without corpus IM or female patients. The 5- and 7-year cumulative risks (95% confidence interval [CI]) for metachronous recurrence were 15.1% (95% CI, 7.7-22.5) and 26.1% (95% CI, 14.9-37.3), respectively, in group 1; 5.6% (95% CI, 3.1-8.1) and 9.3% (95% CI, 5.4-13.2), respectively, in group 2; and 3.8% (95% CI, 1.6-6.0) and 4.9% (95% CI, 2.4-7.4), respectively, in group 3 (P < .001 by log-rank test). The incidence of MGCs increased constantly even after 5 years in groups 1 and 2 but not in group 3. There was not enough evidence to show an association between H pylori eradication and metachronous recurrence in the data. CONCLUSIONS: Meticulous annual endoscopic surveillance for MGC for more than 5 years is recommended for patients with synchronous neoplasm. Endoscopic surveillance may also be extended beyond 5 years in male patients with corpus IM.

Effects of Helicobacter pylori eradication for metachronous gastric cancer prevention: a randomized controlled trial.

BACKGROUND AND AIMS: Whether eradication of Helicobacter pylori reduces the incidence of metachronous gastric cancer (MGC) is still debatable. We aimed to evaluate the long-term effect of H pylori eradication on the development of MGC after endoscopic gastric tumor resection. METHODS: We undertook an open-label, prospective, randomized controlled trial at a tertiary hospital in Seoul, Korea. Participants were recruited during April 2005 to February 2011 and followed until December 2016. We assigned 898 patients with H pylori infection treated with endoscopic resection (ER) for gastric dysplasia or early gastric cancer to receive (n =442) or not receive (n =456) eradication therapy using a random-number chart. Eradication group patients received oral omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg twice daily for a week, whereas control group patients received no H pylori treatment. The primary outcome was the incidence of MGC (intention-to-treat analysis). RESULTS: The 877 patients who attended ≥1 follow-up examination (eradication group, 437; control group, 440) were analyzed. Median follow-up was 71.6 months (interquartile range, 42.1-90.0). MGC developed in 18 (4.1%) eradication and 36 (8.2%) control group patients (log-rank test, P = .01). In our yearly analysis, the effect of eradication showed a significant difference in 5 years after allocation (log-rank test, P = .02). The adjusted hazard ratio for the control group was 2.02 (95% CI, 1.14-3.56; P = .02), compared with the eradication group. CONCLUSIONS: H pylori eradication significantly reduces the incidence of MGC after ER of gastric tumors and should be considered for H pylori-positive gastric tumor patients treated with ER. (Clinical trial registration number: NCT01510730.).

Helicobacter pylori-induced modulation of the promoter methylation of Wnt antagonist genes in gastric carcinogenesis.

BACKGROUND: This study aimed to investigate the changes in the promoter methylation and gene expression of multiple Wnt antagonists between the chronic infection and eradication of Helicobacter pylori (H. pylori) in gastric carcinogenesis. METHODS: The levels of methylation and corresponding mRNA expression of seven Wnt antagonist genes (SFRP1, -2, -5, DKK1, -2, -3, WIF1) were compared among the patients with H. pylori-positive gastric cancers (GCs), and H. pylori-positive and H. pylori-negative controls, by quantitative MethyLight assay and real-time reverse transcription (RT)-polymerase chain reaction (PCR), respectively. The changes of the methylation and expression levels of the genes were also compared between the H. pylori eradication and H. pylori-persistent groups 1 year after endoscopic resection of GCs. RESULTS: The methylation levels of SFRP and DKK family genes were significantly increased in the patients with H. pylori-positive GCs and followed by H. pylori-positive controls compared with H. pylori-negative controls (P < 0.001). SFRP1, -2, and DKK3 gene expression was stepwise downregulated from H. pylori-negative controls, H. pylori-positive controls, and to H. pylori-positive GCs (P < 0.05). Among the Wnt antagonists, only the degrees of methylation and downregulation of DKK3 were significantly reduced after H. pylori eradication (P < 0.05). CONCLUSION: Epigenetic silencing of SFRP and DKK family genes may facilitate the formation of an epigenetic field during H. pylori-associated gastric carcinogenesis. The epigenetic field may not be reversed even after H. pylori eradication except by DKK3 methylation.

Surveillance strategy according to age after endoscopic resection of early gastric cancer.

BACKGROUND: Whether surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) differs in young patients is unclear. This study aimed to evaluate the risk of metachronous and extragastric recurrence in young patients with EGC after curative ESD. METHODS: We retrospectively enrolled 1237 consecutive patients who underwent curative ESD for EGC from 2005 to 2014 at a single tertiary hospital. The patients were divided into group 1 (<50 years of age, n = 86), group 2 (age 50-74, n = 985), or group 3 (≥75 years of age, n = 166). The clinical characteristics and outcomes were compared among the three age groups. RESULTS: Group 1 had more frequent Helicobacter pylori infection (P < 0.001), less frequent intestinal metaplasia (P = 0.021), and more frequent undifferentiated tumors (P = 0.039). Although the 5-year risk of developing metachronous recurrence appeared to be lower in group 1 (2.7%) than in groups 2 (8.6%) or 3 (8.7%), the risk became quite similar at the 7-year follow-up (6.4, 12.7, and 8.7% for groups 1, 2, and 3, respectively; P = 0.409 by log-rank test). Extragastric recurrences developed in only 2 cases in group 2 (0.2%). CONCLUSIONS: Surveillance for metachronous and extragastric recurrence after curative ESD in patients <50 years of age should not be different from that in patients ≥50 years of age. Endoscopic surveillance for metachronous recurrence should be continued for longer than 5 years, even in young patients.

Clinical efficacy of endoscopic ultrasonography for decision of treatment strategy of gastric cancer.

BACKGROUND: Accurate preoperative tumor staging of gastric cancer is indispensable with expansion of indications for laparoscopic surgery and endoscopic resection. It is important to distinguish mucosal cancer (T1a) in smaller lesion and differentiate early gastric cancer (EGC) in larger lesion considering endoscopic resection indication and laparoscopic surgery indication. We evaluated the clinical outcomes of endoscopic ultrasonography (EUS) for the decision of treatment strategy of gastric cancer compared with pathological staging. METHODS: The patients who underwent EUS and surgical or endoscopic resection for gastric cancer were retrospectively reviewed between September 2005 and February 2016. The depth of tumor invasion (T staging) by EUS was compared with the pathological staging after endoscopic or surgical resection. RESULTS: A total of 6084 patients were finally analyzed. The accuracy rates for T1a and EGC were 75.0 and 89.4%, respectively. The overall accuracy of T staging by EUS was 66.3% when divided by T1a, T1b, and over T2. The accuracy of EUS prior to endoscopic resection was 75.1% in absolute indication and 73.1% in expanded criteria, respectively. The accuracy rates for T1a with lesion ≤ 2 cm in miniprobe EUS and EGC with lesion > 2 cm in conventional EUS were 84.6 and 83.2%, respectively. In multivariate analysis, presence of ulcer, large tumor size, and radial EUS were associated with overestimation, and small tumor size and miniprobe were associated with underestimation in T staging. CONCLUSIONS: EUS showed the high accuracy of 84.6% for T1a in lesion ≤ 2 cm in miniprobe EUS and 83.2% for EGC in lesion > 2 cm in conventional EUS, respectively. EUS can be a complementary diagnostic method to determine endoscopic or surgical treatment modality.

Overlap between irritable bowel syndrome and functional dyspepsia including subtype analyses.

BACKGROUND AND AIM: Coexistent gastrointestinal symptom profiles and prevalence or associated factors for the overlap between each functional dyspepsia (FD) and irritable bowel syndrome (IBS) group remain unclear. Thus, the aim of the present study was to evaluate the clinicodemographic features of FD, IBS, and IBS-FD overlap and assess the risk factors thereof, including subtype and genetic polymorphisms for IBS-FD. METHODS: Consecutive patients were enrolled from the outpatient Gastroenterology clinics of Bundang Seoul National University Hospitals in Korea. All gastrointestinal symptoms occurring at least once per week in the previous 3 months were recorded. Diagnostic criteria of functional gastrointestinal disorders were based on the Rome III criteria. Risk factors including genetic polymorphisms of 5-HTTLPR and ADRA2A 1291 G alleles and CCK-1R intron 779T>C were assessed using a multivariate logistic regression model. RESULTS: A total of 632 subjects (278 control subjects, 308 FD, 156 IBS, and 110 who met the criteria for both FD and IBS) were included in this study. Patients with IBS-FD overlap had more severe symptoms (such as bloating, nausea, vomiting, hard or lumpy stools, defecation straining, and a feeling of incomplete bowel movement) and higher depression scores compared with non-overlap patients. Single/divorced or widowed marital status, nausea, bloating, and a feeling of incomplete emptying after bowel movements were independent risk factors for IBS-FD overlap among IBS patients. In contrast, young age, depression, bloating, and postprandial distress syndrome were positively associated with IBS-FD overlap among FD patients. 5-HTTLPR L/L was a risk factor for the co-occurrence of IBS-C among FD patients (OR: 12.47; 95% CI: 2.00-77.75; P = 0.007). CONCLUSIONS: Bloating was a risk factor for IBS-FD overlap. Patients with postprandial distress syndrome have a higher risk of coexisting IBS, particularly constipation-dominant IBS.

Ablation of residual gastric tumor by argon plasma coagulation after endoscopic resection.

BACKGROUND: For residual gastric tumors (RT) found at the treated sites after endoscopic resections (ER), additional treatment options are additional ER, surgery or argon plasma coagulation (APC). Long-term efficacy of APC as the curative modality for RT has not been fully elucidated. This study aimed to investigate the efficacy and long-term outcome of APC for RT with relevant tumor factors. METHODS: Eighty-two patients who received ER for gastric adenocarcinoma or adenoma and were subsequently treated with APC for RT were reviewed retrospectively. Characteristics of the tumors curatively ablated with single-session of APC and the non-curatively ablated were compared by multiple logistic regression analysis. Overall rate of curative ablation and follow-up duration was calculated. RESULTS: Initial tumor size <20 mm [odds ratio for second residual recurrence (OR) 0.16; 95 % confidence interval (CI) 0.039-0.63], en-bloc resection (OR 0.16; 95 % CI 0.039-0.72), histologic complete resection (OR 0.14; 95 % CI 0.028-0.66) and RT with flat or depressed type (OR 0.20; 95 % CI 0.051-0.77) were significantly associated with curative ablation of RT by single-session of APC. Anterior wall or lesser curvature location showed a tendency toward curative APC, but not reached statistical significance (OR 0.36; 95 % CI 0.11-1.16). A total of 60 patients (73.2 %) achieved curative ablation after single-session of APC. Eleven among the patients (n = 22) with second or more residual recurrence achieved curative ablation with one or two more additional sessions of APC. Overall rate of curative ablation was 86.6 % (71/82). From the last APC, the final curative ablation group (n = 71) has been followed up for 49.7 ± 37.4 months. CONCLUSIONS: En-bloc resection, histologic complete resection, RT with flat or depressed type and initial tumor size less than 2 cm can be predictors of favorable clinical outcome of APC as an additional treatment for RT. For selected patients with RT, APC and close monitoring could be a reasonable alternative to immediate resection.

Effect of Helicobacter pylori Eradication and ABO Genotype on Gastric Cancer Development.

BACKGROUND: Evidence is lacking regarding how Helicobacter pylori infection status, eradication history, and ABO blood type affect the development of gastric cancer (GC) given the multifactorial and distinctive etiology according to cancer location (noncardia vs cardia) and histologic type (intestinal vs diffuse-type). We evaluated the effect of H. pylori infection status incorporated with H. pylori eradication history and ABO genotype on GC development according to cancer location and histologic type. METHODS: A case-control study of 997 patients with noncardia GC (NCGC) and 1147 control subjects was performed using risk analyses with 14 factors including H. pylori infection with eradication history and ABO genotype. As final analyses, multivariable logistic regression models were fitted. Additionally, H. pylori infection status with eradication history was tested for its association with age, atrophic gastritis (AG), and intestinal metaplasia (IM). RESULTS: The ABO genotype with the B allele was associated with a significantly lower risk of NCGC of both histologic types. The reduction in risk for NCGC by adding the B allele was more prominent in diffuse-type than that in the intestinal-type. H. pylori infection with eradication history was associated with a significantly lower risk of NCGC of both histologic types, compared with those without eradication history (odds ratio (OR), 0.22; 95% confidence interval (CI), 0.14-0.34) approaching that of uninfected subjects. Past infection status without an eradication history was associated with older age, AG, and IM. CONCLUSIONS: H. pylori eradication and the B allele decreased the risks of the intestinal and diffuse-types of NCGC. H. pylori eradication revealed a strong association against developing NCGC. Therefore, it should be considered as a primary measure in NCGC prevention.

Analysis of Gastric Microbiota by Pyrosequencing: Minor Role of Bacteria Other Than Helicobacter pylori in the Gastric Carcinogenesis.

BACKGROUND: Little is known about the role of gastric microbiota except for Helicobacter pylori (HP) in human health and disease. We compared the differences of human gastric microbiota according to gastric cancer or control and HP infection status and assessed the role of bacteria other than HP. METHODS: Gastric microbiota of 63 antral mucosal and 18 corpus mucosal samples were analyzed by bar-coded 454 pyrosequencing of the 16S rRNA gene. Antral samples were divided into four subgroups based on HP positivity in pyrosequencing and the presence of cancer. The analysis was focused on bacteria other than HP, especially nitrosating or nitrate-reducing bacteria (NB). The changes of NB in antral mucosa of 16 subjects were followed up. RESULTS: The number of NB other than HP (non-HP-NB) was two times higher in the cancer groups than in the control groups, but it did not reach statistical significance. The number of non-HP-NB tends to increase over time, but this phenomenon was prevented by HP eradication in the HP-positive control group, but not in the HP-positive cancer group. CONCLUSION: We could not find the significant role of bacteria other than HP in the gastric carcinogenesis.

Patients with perianal Crohn's disease have poor disease outcomes after primary bowel resection.

BACKGROUND AND AIM: The presence of perianal disease in Crohn's disease patients is one of the factors of postoperative recurrence. The aim of this study is to evaluate long-term prognosis of perianal Crohn's disease patients in Asian. METHODS: Patients with Crohn's disease who had undergone surgical bowel resection were divided into two groups according to the presence of perianal lesion. We monitored the occurrences of abdominal and/or perianal reoperation and readmission due to disease flare-up. RESULTS: The 132 patients included in the study were divided into 2 groups, those with perianal disease (45 patients, 34.1%) and those without perianal disease (87 patients, 65.9%). Patients with perianal disease was younger in age (33.8 years versus 39.8 years, p = 0.015) and had been diagnosed as CD at a younger age (21.9 years versus 28.6 years, p = 0.005) than patients without perianal disease. Patients with perianal disease showed more extra-intestinal manifestation than patients without perianal disease (8 versus 3, p = 0.008). Reoperation was required in 46 (44.8%) patients during the follow-up period. The presence of perianal disease independently increased the risk of reoperation [hazard ratio (HR), 3.112; confidence interval (CI), 1.707-5.675]. Furthermore, patients with perianal disease had increasing risks of abdominal reoperation (HR 1.978; 95% CI, 1.034-3.784). CONCLUSIONS: Patients with Crohn's disease and perianal lesions had a higher risk of reoperation. Considering these findings, physicians should consider aggressive and early top down therapy for patients with perianal Crohn's disease.

Follow-Up Study on CDX1 and CDX2 mRNA Expression in Noncancerous Gastric Mucosae After Helicobacter pylori Eradication.

BACKGROUND: Changes in CDX1/CDX2 in gastric mucosae following Helicobacter pylori eradication have not been clarified yet. AIMS: To evaluate the changes in CDX1/CDX2 expression after H. pylori eradication, in relation to the reversibility of intestinal metaplasia (IM). METHODS: Time course of CDX1/CDX2 expressions was investigated in 176 subjects with various gastroduodenal disorders. Among them, 132 patients were H. pylori positives; H. pylori were eradicated in 107 of them; 13 failed to eradicate; and 12 did not receive H. pylori eradication therapy. Forty-four subjects were H. pylori negatives. Expression levels in CDX1 and CDX2 from noncancerous gastric mucosae of the corpus, as well as the histologic findings of gastric mucosae, were evaluated during the follow-up. RESULTS: Average follow-up duration was 33.7 months (range 2-97 months). Expression levels in both CDX1 and CDX2 mRNAs were correlated with IM grade in the corpus (ρ = 0.633 and 0.554, respectively, all P < 0.001). Changes in CDX1/CDX2 mRNA expressions following H. pylori eradication showed only insignificant results; IM grade at the antrum and corpus showed a tendency to decrease after H. pylori eradication without statistical significance (P > 0.05). However, histologic improvement of IM at the corpus was associated with a decrease in CDX2 mRNA expression during the follow-up (linear mixed model, P for slope = 0.015). CONCLUSIONS: In this study, eradication of H. pylori did not show any beneficial effects on aberrant CDX1/CDX2 expressions or IM. Reversibility of IM may be associated with a decrease in CDX2 mRNA expression.

Clinical outcomes of re-stenting in patients with stent malfunction in malignant gastric outlet obstruction.

BACKGROUND AND AIMS: Self-expanding metal stents (SEMS) have been used for the palliative treatment of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the clinical outcomes of salvage SEMS for stent malfunction and to identify the prognostic factors for a longer patency. METHODS: A total of 108 patients who underwent a secondary salvage SEMS placement for a primary stent malfunction were retrospectively reviewed at the Seoul National University Hospital between August 2004 and May 2013. The duration of patency for salvage SEMS was defined as the time between salvage SEMS placement and the recurrence of obstructive symptoms that were confirmed either endoscopically or radiologically. RESULTS: The technical and clinical success rates for salvage SEMS were 100 and 82.4% (95% confidence interval [CI] 74.0-89.0), respectively. A salvage SEMS malfunction occurred in 29 (26.9%) of the 108 patients. The median duration of patency for salvage SEMS was 59.5 days (range 3-928, 95% CI 73.7-118.3). Longer SEMS patencies of more than 60 days were significantly associated with palliative chemotherapy (odds ratio = 2.539, 95% CI 1.031-6.252, p = .043). For salvage SEMS, covered-uncovered stents had a longer patency duration, as compared with other combinations of primary and salvage stent types. CONCLUSIONS: Longer patency durations for salvage SEMS were associated with palliative chemotherapy after salvage SEMS insertion. Salvage SEMS could be a feasible and effective treatment for primary stent malfunction in malignant GOO.

Endoscopic predictors for undifferentiated histology in differentiated gastric neoplasms prior to endoscopic resection.

BACKGROUND: There is often a discrepancy between results from endoscopic forceps biopsy and resected specimen. We aimed to identify endoscopic predictors for undifferentiated histology in differentiated gastric neoplasms prior to endoscopic resection. METHODS: Medical records of the patients who underwent endoscopic submucosal dissection (ESD) for biopsy-proven differentiated gastric neoplasms at Seoul National University Hospital between July 2005 and July 2014 were retrospectively reviewed. The lesions were divided into two groups based on the final histologic result of ESD: differentiated adenocarcinoma (DA group) and undifferentiated histology (UDH group). The discordant rate, clinicopathologic characteristics, and endoscopic factors were analyzed. RESULTS: A total of 1641 early gastric cancers from 1615 patients were included. Of these, 1556 (94.8%) were diagnosed as DA and 85 (5.2%) as UDH. The mean age was significantly lower, and number of women was higher in the UDH group than in the DA group. On multivariate analysis, age <65 years [odds ratio (OR) 1.75, 95 % confidence interval (CI) 1.10-2.80], female sex (OR 3.19, 95% CI 2.00-5.08), endoscopic size >10 mm (OR 1.81, 95% CI 1.12-2.92), depressed type (OR 2.85, 95% CI 1.56-5.21), nodularity (OR 2.83, 95% CI 1.59-5.05), and whitish discoloration (OR 19.64, 95% CI 6.98-55.25) were independent predictors. CONCLUSIONS: Female sex, age <65 years, large endoscopic size, depressed morphology, surface nodularity, and whitish discoloration were predictors for UDH. Meticulous attention should be paid to the lesions with these endoscopic predictors for determining the risk of UDH prior to endoscopic resection.

Clinical outcomes of no residual disease in the specimen after endoscopic resection for gastric neoplasms.

BACKGROUND: No residual disease (NRD) can be found in the specimen after endoscopic resection (ER) of biopsy-proven gastric neoplasm. This study aimed to evaluate the endoscopic and pathologic characteristics of patients with NRD and identify the cause and long-term prognosis. METHODS: Medical records of patients who underwent ER for biopsy-proven gastric neoplasms at a single tertiary hospital between January 2005 and November 2014 were retrospectively reviewed. Patients whose post-ER histology was revealed as NRD were included. Overall incidence, clinicopathologic characteristics, cause, and long-term prognosis were analyzed. RESULTS: NRD was detected in 143 (3.2%) of 4401 cases of gastric neoplasms treated with ER. Mean endoscopic size of the initial lesion was 8.15 ± 6.64 mm; in 93 cases (65.0%), the lesion was located in the lower third of the stomach. Initial pathologic diagnosis was as follows: adenoma (n = 110), carcinoma (n = 29), and atypical gland (n = 4). The causes of NRD were minute lesions removed by biopsy in 140 patients, pathologic misdiagnoses in two, and localization error in one. Local recurrence was detected in five patients (3.6%) with minute lesions during follow-up and treated with argon plasma coagulation (n = 4) or re-ER (n = 1). Synchronous (n = 5, 3.6%) and metachronous gastric lesions (n = 6, 4.3%) were also detected during follow-up. CONCLUSIONS: The main cause of NRD was minute lesions which might be completely removed by initial diagnostic biopsy. These cases showed a minimal rate of local recurrence and synchronous or metachronous gastric neoplasms. Careful follow-up is also mandatory for detection of residual disease.

Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells.

We know little concerning the expression of transforming growth factor-ß1 (TGF-ß1) and TGF-ß1-induced epithelial-mesenchymal transition (EMT) markers in gastric mucosa and their changes after eradication of Helicobacter pylori infection have not yet been clarified. In the present study, we compared the time course of messenger RNA (mRNA) expression of TGF-ß1 and five EMT markers (Twist, Snail, Slug, vimentin and E-cadherin) in 111 controls, 55 patients with gastric dysplasia and 71 patients with early gastric cancer, following eradication of H.pylori. mRNA levels in non-cancerous gastric mucosa were measured using quantitative real time-polymerase chain reaction and the histologic findings of gastric mucosa were compared before and after eradication. The average duration of follow-up was 46.7 months (6.0-112.4). The levels of TGF-ß1, Twist, Snail, Slug and vimentin mRNA, in addition to levels of CD44 detected by immunohistochemistry, showed all up-regulation in patients with dysplasia or early gastric cancer compared with controls (P < 0.05); moreover, the mRNA levels of E-cadherin, an epithelial marker, were decreased in these patients compared with the control group (P < 0.001). Eradication of H.pylori reduced the expression of TGF-ß1, Twist, Snail, Slug and vimentin mRNA (P-value for slope <0.001), as well as the immunohistochemical expression of CD44 (P = 0.014), whereas it enhanced the expression of E-cadherin (P-value for slope < 0.05). Thus, H.pylori infection may trigger the TGF-ß1-induced EMT pathway and the emergence of gastric cancer stem cells (CSCs). Its eradication may prevent the carcinogenesis of gastric cancer by inhibiting these two pathways.

High Efficacy of Finafloxacin on Helicobacter pylori Isolates at pH 5.0 Compared with That of Other Fluoroquinolones.

Finafloxacin is a novel fluoroquinolone with improved antimicrobial efficacy, especially in an acidic environment. The efficacy of finafloxacin for the inhibition of Helicobacter pylori infection was compared with the efficacies of levofloxacin and moxifloxacin at neutral and acidic pH. The impacts of gyrA point mutation on the efficacy of those three fluoroquinolones were also investigated. A total of 128 clinical H. pylori strains were utilized. MICs of levofloxacin, moxifloxacin, and finafloxacin were determined at pH 5.0 and pH 7.0 by the agar dilution method. The impact of gyrA point mutations that are responsible for fluoroquinolone resistance was analyzed; the results showed 50 strains with an Asn-87 point mutation, 48 strains with an Asp-91 point mutation, and the remaining 30 strains with no gyrA mutations. The use of finafloxacin led to MIC values at pH 5.0 that were lower than the values seen at pH 7.0 for 112 strains (112/128, 87.5%), and this proportion was higher than that seen with moxifloxacin (21/128, 16.4%, P < 0.001). Finafloxacin also demonstrated a rate of susceptibility (MIC, <1 µg/ml) (37.5%, 48/128) at pH 5.0 that was higher than that seen with moxifloxacin (2.3%, 3/128) (P < 0.001). The trends were similar regardless of which of the Asn-87, Asp-91, and A2143 point mutations were present. In conclusion, the superior antimicrobial efficacy of finafloxacin against H. pylori in an acidic environment suggests the possible use of finafloxacin for treatment of H. pylori infection, as has been proposed by its developer, Merlion Pharma.

Novel risk stratification for recurrence after endoscopic resection of advanced colorectal adenoma.

BACKGROUND: Advanced colorectal adenoma (ACA) refers to adenomas with the following predictive characteristics: ≥1 cm in diameter, and/or villous component, and/or high-grade dysplasia. ACA has high risk of transforming to colorectal cancer, and the recurrence rate is relatively high. OBJECTIVE: To assess the outcomes of patients with ACA undergoing endoscopic resection and to identify risk factors for local recurrence and development of metachronous advanced neoplasm. DESIGN: Retrospective cohort study. SETTING: Tertiary care medical center. PATIENTS: From 2005 to 2011, the records of 3625 patients who underwent colonoscopic polypectomy at Seoul National University Hospital were retrospectively reviewed. Patients with synchronous colorectal cancers, inflammatory bowel disease, previous colorectal resection, loss to follow-up, and incomplete resection were excluded. INTERVENTION: Endoscopic resection for ACA. MAIN OUTCOME MEASUREMENTS: Local recurrence and metachronous advanced neoplasm. RESULTS: The study included 917 patients with 1206 ACAs. The median duration of follow-up was 28.5 months (interquartile range, 12.8-51.7). Independent risk factors for local recurrence included ACA with 2 or more predictive characteristics (adjusted hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.11-5.48; P = .027) and piecemeal resection (adjusted HR, 6.96; 95% CI, 1.58-30.71; P = .010). Independent risk factors for metachronous advanced neoplasm were male gender (adjusted HR, 1.65; 95% CI, 1.02-2.65; P = .041), ≥3 adenomas (adjusted HR, 2.56; 95% CI, 1.72-3.82; P < .001), and ≥3 ACAs (adjusted HR, 1.44; 95% CI, 1.01-2.06; P = .045). LIMITATIONS: Retrospective design. CONCLUSION: ACAs with 2 or more predictive characteristics recurred locally at a higher rate than ACAs with 1 predictive characteristic. These results suggest that patients who are found to have ACAs with 2 or more predictive factors at index colonoscopy are at higher risk for local recurrence, and follow-up colonoscopy should be performed sooner.