Sex-specific differences in colorectal cancer: A multicenter retrospective cohort study.

BACKGROUND: Due to sex-specific differences in the incidence and clinical and histopathological characteristics of colorectal cancer (CRC), understanding the impact of sex on CRC may suggest sex-targeted strategies for screening, treatment, and prevention, leading to improved prognosis of CRC. However, there have been few studies investigating the sex-specific differences in CRC in the Republic of Korea. We aimed to assess sex differences in CRC in the Republic of Korea. METHODS: This was a retrospective, multicenter, cohort study of patients diagnosed with CRC between January 2012 and December 2013 at nine hospitals. Patients who had an uncertain CRC stage, were diagnosed with other cancers within 5 years, had carcinoma in situ, non-epithelial cancer, or primary cancer other than CRC, were excluded. Factors associated with overall survival or progression-free survival were investigated using Cox regression analysis. Cumulative probability of metachronous lesions was compared using the Kaplan-Meier estimator survival analysis and we compared the survival curves of each group using a log-rank test. Outcomes were compared using the chi-square, Fisher's exact, or Student's t-test, as appropriate. RESULTS: Three thousand one hundred and forteen patients (1999 men, 1315 women) were included. There was no significant difference in the age at onset between men and women. The proportion of patients diagnosed through regular health check-ups, and asymptomatic at time of diagnosis, was higher in men (48.9% men vs. 42.0% women, p < .001). Rectal cancers were more common in men (38.8% men vs. 31.8% women, p < .001). Right colon cancers were more common in women (31.4% women vs. 22.7% men, p < .001). KRAS mutations were found in 109/317 (34.4%) women and 112/480 (23.3%) men. Overall CRC survival and progression-free survival were similar in both sexes. CONCLUSION: Sex differences in CRC may be due to the biological and social-behavioral differences between the sexes. They should be considered during screening, diagnosis, and treatment of CRC for better outcomes.

What Is Most Important to the Endoscopist for Therapeutic Plan? Morphology versus Pathology: A Nationwide Multicenter Retrospective Study in Korea.

Histologic discrepancy may sometimes occur between biopsy and endoscopic resection. We investigated the discrepancy rate between the biopsy and the resection lesion in the Korean population. From January 2010 to October 2016, 268 patients with gastric endoscopic mucosal resection/endoscopic submucosal dissection history from nationwide hospitals were enrolled retrospectively. We compared the histologic discrepancy rates from the biopsy and the resection. The mean age was 63.2 years. Gastric adenomas occurred most frequently in the antrum. The pathology of the resected specimens classified 25 lesions (9.3%) as gastritis/hyperplasia, 146 lesions (54.5%) as low-grade dysplasia, 76 lesions (28.4%) as high-grade dysplasia (HGD), and 21 lesions (7.8%) as adenocarcinoma. The discrepancy rate between biopsy and resection was 23.1 per cent. Among the 44 cases of gastritis/hyperplasia, two cases (4.5%) were diagnosed as HGD and 11 cases (25.0%) were diagnosed as cancer after resection. Among the 182 cases of low-grade dysplasia, 33 cases (18.1%) were diagnosed as HGD and nine cases (5.0%) were diagnosed as cancer after resection. Gastritis/hyperplasia, ulceration, and lesions in the lower body location were significant factors related to the discrepancies. Especially, discrepancy occurred most frequently in gastritis/hyperplasia lesions with ulcer in the lower body. There was considerable histologic discrepancy between biopsy and resection. Ulcerative-type tumor morphology and biopsy diagnosis of gastritis/hyperplasia are suggestive factors predictive of discrepancy between biopsy and resection in terms of malignancy. Therefore, although the results of biopsy are gastritis/hyperplasia, suspicious tumorous lesions with ulcer should be indicative of active endoscopic resection for diagnosis and treatment.

Catalytic reactivity of an iridium complex with a proton responsive N-donor ligand in CO2 hydrogenation to formate.

Catalytic hydrogenation of CO2 into formic acid/formate is an attractive conversion in the utilization of CO2. Although various catalysts with high catalytic efficiency are reported, a very few studies have been carried out to correlate/understand the efficacy and stability of the hydrogenation catalysts, which could be helpful to direct the future design strategy of corresponding catalysts. Herein, a half-sandwich iridium complex containing bibenzimidazole as a proton responsive N-donor ligand, [Cp*Ir(BiBzImH2)Cl]Cl, has been synthesized and fully characterized. The generation of an N- anion by the deprotonation of a bibenzimidazole group resulted in a significant enhancement of activity. The Ir complex showed about 20 times higher catalytic efficiency in the hydrogenation of CO2 into formate than that of its bipyridine counterpart [Cp*Ir(Bpy)Cl]Cl. The time dependent catalytic activity studies revealed that the initial excellent activity of [Cp*Ir(BiBzImH2)Cl]Cl was reduced when catalytic cycle proceeds; which was found to be the structural instability of the catalyst caused by steric hindrance between the bibenzimidazole and Cp* ligands.

Cerebral venous thrombosis in a patient with Crohn's disease.

Patients with inflammatory bowel disease (IBD) have an elevated risk of venous thromboembolism compared with the general population. The most common sites of venous thromboembolism in IBD patients are the deep veins of the legs, the pulmonary system, and portal and mesenteric veins. However, cerebral venous thrombosis is rarely associated with IBD. This report describes a case of cerebral venous thrombosis in a patient with Crohn's disease. A 17-year-old girl, diagnosed 4 years earlier with Crohn's disease, presented with headache and vomiting. Magnetic resonance imaging of the brain with venography showed venous thrombosis in the cortical veins, superior sagittal sinus, right transverse sinus, and right internal jugular vein. The patient immediately started anticoagulation therapy with intravenous heparin infusion followed by daily oral rivaroxaban 10 mg. Follow-up imaging after 2 weeks showed resolution of the thrombosis, with recanalization of the cortical veins, superior sagittal sinus, right transverse sinus, and right internal jugular vein. She continued rivaroxaban therapy for 6 months, and remained well, without neurologic sequelae. A high level of concern for cerebral venous thrombosis may be important when treating active IBD patients, because anticoagulation treatment can prevent fatal complications.

Successful en bloc resection of an esophageal hemangioma by combined EBL & EMR: a case report and technical review.

A 58-year-old male was diagnosed esophageal hemangioma during a endoscopy in regular examination. The patient was referred to the department of gastroenterology in our hospital to treatment. Combined endoscopic band ligation (EBL) and endoscopic mucosal resection (EMR) was performed for diagnostic treatment. Histopathological results revealed hemangioma. Even though several approaches such as esophagectomy, endoscopic removal, sclerotherapy, and laser therapy have been used to remove the esophageal hemangiomas, recently less invasive methods were preferred. Here we describe a case of esophageal hemangioma removed by EBL & EMR.

Usefulness and feasibility of endoscopic submucosal dissection for colorectal tumor: a nationwide multicenter retrospective study in Korea.

BACKGROUND: Detection rate of precursor lesion of colorectal cancer and early colon cancer have recently been rising because of increased screening endoscopy and increased incidence of colorectal cancer. Endoscopic submucosal dissection (ESD) technique has been reported to be useful in the treatment of such superficial lesions in colon. However, nationwide multicenter study for usefulness and feasibility of colorectal ESD is still limited. METHODS: From January 2009 to February 2014, colorectal ESD data performed at nationwide university hospitals were enrolled in retrospective design. Demographic, clinical, technical data, and data of complications were reviewed. RESULTS: A total of 189 patients were included with 191 lesions resected by colorectal ESD. The indications were epithelial lesions (n=120), neuroendocrine tumor (n=25), cancer (n=46). The lesion locations were right colon (n=45), transverse colon (n=17), descending colon (n=8), sigmoid colon (n=33), rectum (n=88). The median size of the lesions was 21.1 mm. En bloc resection rate of the lesion was 83.3%, with complete R0 resection in 73.3%. The median duration of ESD was 53.7 minutes. Factor related to En bloc resection was tumor location (right colon/transverse colon 72.6% vs. other location 89.2%, P=0.004). Factors related complication were tumor location (right colon/transverse colon 12.9% vs. Other location 10.13%, P=0.044) and tumor size (without complication 20.5±10.2 mm vs. with complication 25.9±11.7 mm, P=0.027). The short term morbidity rate was 11.0% including 5 hemorrhages (2.6%) and 16 perforations (8.4%). CONCLUSIONS: In this study, ESD shows promise as a useful, potentially feasible procedure in colorectal superficial tumor because of high en bloc resection rate and low morbidity rate, especially in small lesions located from descending colon to rectum.

[A Case of Cavernous Lymphangioma of the Small Bowel Mesentery].

Lymphangioma is a benign vascular lesion with characteristics of subepithelial tumor which can proliferate in the lymphatic system. Lymphangioma of the small-bowel mesentery is rare, having been reported in less than 2% of all lymphangiomas. Lymphangioma does not require any specific treatment because it is absolutely a benign tumor. However, surgical exploration is rarely required for cases with disease-related symptoms or complications, or for those misdiagnosed as a malignant lesion. We recently experienced a case of mesenteric cavernous lymphangomas in a 53-year-old female who was misdiagnosed as having a liposarcoma. The final diagnosis was confirmed by a pathologic examination of the specimen that was obtained via laparoscopic exploration. Herein, we report a very rare case of mesenteric cavernous lymphangioma along with a brief review of relevant literature.

A Patient with Duodenal Mucinous Adenocarcinoma Presenting as a Laterally Spreading Tumor.

Primary duodenal carcinoma is rare. Duodenal mucinous adenocarcinoma (DMA) is even rarer, and its associated manifestations and typical endoscopic or imaging findings are not well characterized. Herein, we report a case of primary DMA in an asymptomatic 58-year-old man who visited our hospital for a regular health screening. Upper endoscopy revealed an approximately 4-cm lesion in the second portion of the duodenum, but the mass was not visualized on computed tomography. Biopsies revealed a tubular adenoma that was subsequently resected. Frozen biopsies demonstrated DMA with a background of low-grade tubular adenoma for which we performed Roux-en-Y duodenojejunostomy and jejunojejunostomy. To our knowledge, this is the first report of a patient with DMA in Korea.

High-risk metachronous polyps are more frequent in patients with traditional serrated adenomas than in patients with conventional adenomas: a multicenter prospective study.

BACKGROUND AND AIMS: Although the malignant progression of serrated polyps has been clearly documented, the malignant potential of the traditional serrated adenoma (TSA) subtype has not been established. We compared the prevalence of metachronous polyps in surveillance colonoscopies between patients with TSA and those with conventional adenomas (CAs). METHODS: Four hundred twenty patients were diagnosed with TSAs by current diagnostic criteria at 10 tertiary care university hospitals in Korea from January 2003 to December 2005; 186 patients who received surveillance colonoscopy after removal of initial polyps were enrolled. During the same time period, 372 age- and sex-matched patients diagnosed with CAs were used as a control group. RESULTS: TSA patients had a significantly higher recurrence rate of colorectal polyps compared with CA patients (66.1% vs 43.5%, respectively). TSA patients had a greater number (3 vs 2) and larger size (8.6 ± 5.7 vs 6.3 ± 5.2 mm) of recurrent polyps compared with CA patients. TSA patients also had a higher rate of CA (54.8% vs 37.9%), serrated adenoma (14.0% vs. 0.8%), and hyperplastic polyp (33.3% vs. 13.7%) recurrence compared with CA patients. TSA patients had significantly greater odds of having a recurrent high-risk polyp than CA patients (odds ratio, 2.37; 95% confidence interval, 1.55-3.63). CONCLUSIONS: In comparison with patients with CAs, patients with TSAs have a higher metachronous occurrence rate of all polyp subtypes including CAs, serrated adenomas, and hyperplastic polyps. Moreover, the presence of TSAs is an independent predictor of a high-risk polyp occurrence.

Anaphylactic shock caused by ingestion of polyethylene glycol.

Colonoscopy is the current standard method for evaluation of the colon. The diagnostic accuracy and therapeutic safety of colonoscopy depend on the quality of colonic cleansing and preparation. Generally, all these preparations have been demonstrated to be safe for use in healthy individuals without significant comorbid conditions. Based on safety and efficacy concerns, polyethylene glycol (PEG) is most commonly utilized as a bowel preparation solution for colonoscopy. Adverse events in patients receiving PEG are mostly clinically non-significant. However, fatal adverse events rarely have been shown to occur in the few individuals who experience vomiting or aspiration. Anaphylactic shock associated with ingestion of PEG electrolyte solution is an extremely rare fatal complication, and reported mainly in Western countries. Here, we report the first case of anaphylactic shock following the ingestion of PEG solution in Korea.

Is annual endoscopic surveillance necessary for the early detection of gastric remnant cancer in Korea? A retrospective multi-center study.

BACKGROUND/AIMS: This study investigated the clinical characteristics, survival outcomes of the patients with gastric remnant cancers (GRC) diagnosed after gastric cancer surgery and the need of annual endoscopic surveillance after gastric resection for early detection of GRC. METHODOLOGY: We reviewed the medical records of 30 patients who underwent endoscopy and diagnosed with GRC between 1999 and 2009. We analyzed the clinical features, tumor characteristics, regular endoscopic surveillance, treatment, and survival outcomes. RESULTS: The median time interval between first operation and diagnosis of GRC was 36 months. Fifteen patients (50%) had GRC at non-anastomotic sites. Seventeen patients (56.7%) underwent annual endoscopic surveillance and nine patients (30%) had no symptom at the time of diagnosis of GRC. GRC were detected earlier in patients with annual endoscopic surveillance than those without surveillance (p=0.0014). The median overall survival (OS) after the diagnosis of GRC for all patients was 35.9 months. The median OS of patients with curative resection including endoscopic resection for early gastric cancer was longer than those without resectability (46.3 vs. 13.6 months, p=0.0026). CONCLUSIONS: These results suggest that annual endoscopic surveillance program after gastric partial resection would be helpful to detect early cancer of remnant stomach for curative resection.

[Efficacy of fenoverine and trimebutine in the management of irritable bowel syndrome: multicenter randomized double-blind non-inferiority clinical study].

BACKGROUND/AIMS: Antispasmodic agents have been used in the management of irritable bowel syndrome. However, systematic reviews have come to different conclusions about the efficacy in irritable bowel syndrome. Fenoverine acts as a synchronizer of smooth muscle in modulating the intracellular influx of calcium. We compared fenoverine with trimebutine for the treatment of patients with IBS. METHODS: A multicenter, randomized, double-blind, non-inferiority clinical study was conducted to compared fenoverine with trimebutine. Subjects were randomized to receive either fenoverine (100 mg three times a day) or trimebutine (150 mg three times a day) for 8 weeks. A total of 197 patients were analyzed by the intention-to-treat approach. The primary endpoint was the proportion of patients who had 30% reduction in abdominal pain or discomfort measured by bowel symptom scale (BSS) score at week 8 compared to the baseline. The secondary endpoints were changes of abdominal bloating, diarrhea, constipation, overall and total scores of BSS, and overall satisfaction. RESULTS: At week 8, fenoverine was shown to be non-inferior to trimebutine (treatment difference, 1.76%; 90% CI, -10.30-13.82; p=0.81); 69.23% (54 of 78 patients) of patients taking fenoverine and 67.47% (56 of 83 patients) of patients taking trimebutine showed 30% reduction in abdominal pain or discomfort compared to the baseline. There results of the secondary endpoints were also comparable between the fenoverine group and the trimebutine group. CONCLUSIONS: Fenoverine is non-inferior to trimebutine for treating IBS in terms of both efficacy and tolerability.

Successful endoscopic band ligation of esophageal perforation by fish bone ingestion.

Acute esophageal perforations by foreign body ingestion result in complications such as mediastinitis and retropharyngeal or parapharyngeal abscesses. Because the mortality of esophageal perforation is up to 22%, immediate treatment is critical. Herein, we report a case of successful endoscopic band ligation of esophageal perforation. A 68-year-old man was admitted complaining of substernal pain and dysphagia after ingesting a fish bone. Immediately emergency endoscopy was performed, and the fish bone was observed lodged in the lower esophagus. Although the fish bone was easily removed by an endoscopic rat-tooth forceps, esophageal perforation was found after the procedure. Endoscopic band ligation for perforation was performed. Initial chest computed tomography (CT) showed pneumomediastinum and local inflammation, but follow-up CT showed improved pneumomediastinum. The patient was given oral nutrition 2 weeks after procedure, and he was discharged without any complications. This case report emphasizes for the first time the availability of immediate endoscopic band ligation for acute esophageal perforation.

Carbonic anhydrase promotes the absorption rate of CO2 in post-combustion processes.

The rate of carbon dioxide (CO2) absorption by monoethanol amine (MEA), diethanol amine (DEA), N-methyl-2,2'-iminodiethanol (MDEA), and 2-amino-2-methyl 1-propanol (AMP) solutions was found to be enhanced by the addition of bovine carbonic anhydrase (CA), has been investigated using a vapor-liquid equilibrium (VLE) device. The enthalpy (-ΔHabs) of CO2 absorption and the absorption capacities of aqueous amines were measured in the presence and/or absence of CA enzyme via differential reaction calorimeter (DRC). The reaction temperature (ΔT) under adiabatic conditions was determined based on the DRC analysis. Bicarbonate and carbamate species formation mechanisms were elucidated by (1)H and (13)C NMR spectral analysis. The overall CO2 absorption rate (flux) and rate constant (kapp) followed the order MEA > DEA > AMP > MDEA in the absence or presence of CA. Hydration of CO2 by MDEA in the presence of CA directly produced bicarbonate, whereas AMP produced unstable carbamate intermediate, then underwent hydrolytic reaction and converted to bicarbonate. The MDEA > AMP > DEA > MEA reverse ordering of the enhanced CO2 flux and kapp in the presence of CA was due to bicarbonate formation by the tertiary and sterically hindered amines. Thus, CA increased the rate of CO2 absorption by MDEA by a factor of 3 relative to the rate of absorption by MDEA alone. The thermal effects suggested that CA yielded a higher activity at 40 °C.

Endoscopic submucosal dissection as a treatment for gastric subepithelial tumors that originate from the muscularis propria layer: a preliminary analysis of appropriate indications.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a well-established method for the treatment of gastrointestinal epithelial tumors. However, the treatment of gastric subepithelial tumors (SETs) that originate from the muscularis propria layer still depends primarily on surgical techniques. We evaluated the appropriate indications for ESD in the treatment of SETs that originate from the muscularis propria layer. METHODS: Thirty-five patients with gastric SETs that originate from the muscularis propria layer who underwent ESD were enrolled, and the charts were retrospectively reviewed to investigate the parameters predictive complete resection and complications. RESULTS: The mean age of the patients was 54.15 ± 9.3 years, and the male/female ratio was 2:3. Twenty-eight of the 35 SETs (85.7%) were movable, and 15 (45.7%) had a positive rolling sign. The most frequent location of the SETs was high body (n = 14). The most common pathological diagnoses were leiomyoma (60%) and gastrointestinal stromal tumor (28.6%). The complete resection rate was 74.3%. A positive rolling sign (p = 0.022) and small tumor size (≤20 mm; p = 0.038) were significantly associated with complete resection. Two patients (6.1 %) developed perforations that required surgical treatment; their SMTs were neurogenic tumors with fixed lesion. Tumor mobility was significantly associated with perforation (p = 0.017). CONCLUSIONS: The ESD method appears to be relatively safe for use in the complete resection of SETs that originate from the muscularis propria layer. Small tumor size (≤20 mm) and a positive rolling sign are appropriate indications for ESD.

Safety and efficacy of deep sedation with propofol alone or combined with midazolam administrated by nonanesthesiologist for gastric endoscopic submucosal dissection.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is accepted as a treatment for gastric neoplasms and usually requires deep sedation. The aim of this study was to evaluate the safety and efficacy profiles of deep sedation induced by continuous propofol infusion with or without midazolam during ESD. METHODS: A total of 135 patients scheduled for ESDs between December 2008 and June 2010 were included in this prospective study and were randomly assigned to one of two groups: the propofol group or the combination group (propofol plus midazolam). RESULTS: The propofol group reported only one case of severe hypoxemia with no need of mask ventilation or intubation. Additionally, 18 cases of mild hypotension were observed in the propofol group, and 11 cases were observed in the combination group. The combination group had a lower mean total propofol dose (378 mg vs 466 mg, p<0.012), a longer mean recovery time (10.5 minutes vs 7.9 minutes, p=0.027), and a lower frequency of overall adverse events (32.8% vs 17.6%, p=0.042). CONCLUSIONS: Deep sedation induced by continuous propofol infusion was shown to be safe during ESD. The combination of continuous propofol infusion and intermittent midazolam injection can decrease the total dose and infusion rate of propofol and the overall occurrence of adverse events.

Colonic mucosal pseudolipomatosis: disinfectant colitis?

Colonic pseudolipomatosis is rare and its pathogenesis is still unclear. A number of mechanisms, including mechanical injury during an endoscopic procedure or chemical injury by disinfectant, seem to contribute to its pathogenesis. In our endoscopy unit, pseudolipomatosis occurred in an epidemic pattern after changing the endoscopic disinfectant from 2% glutaraldehyde to peracetic acid compound to decrease the length of endoscope reprocessing time. We assumed that pseudolipomatosis could be a type of chemical colitis produced by the residual disinfectant solution that remained on the surface or in a channel of the endoscope after reprocessing. The aim of this report was to highlight a series of 12 cases of colonic pseudolipomatosis in order to describe the endoscopic and pathological features and discuss the harmful effect of disinfectants as a possible cause of pseudolipomatosis. To identify the cause of the lesions, we systematically reviewed each patient history and the endoscopic and histological features. From March 2004 to February 2005, 1276 colonoscopies were performed and 12 cases (0.94%) of colonic pseudolipomatosis were diagnosed at the Kangnam Sacred Heart Hospital of Hallym University. The pathogenesis of colonic pseudolipomatosis is not well-known, but our experience indicates the endoscopic disinfectant as the probable cause of pseudolipomatosis rather than either mechanical traumatic injury or intraluminal air pressure-related injury.

Prevalence of minimal change lesions in patients with non-erosive reflux disease: a case-control study.

BACKGROUND/AIMS: Some minimal changes (MCs) are believed to have a certain relationship with gastroesophageal reflux (GERD). Nonetheless, the individual meaning of MC is still unclear. Our aim was to compare the overall and individual prevalence of MC between patients with non-erosive reflux disease (NERD) and healthy controls (HC). METHODS: Twelve endoscopic findings in the esophagogastric junction were prospectively compared between NERD (n = 64) and control (n = 104). RESULTS: Overall frequency of MC (≥ 1 out of 12 criteria) was higher in the NERD group (71.9%) than in the HC group (45.2%). In individual analysis, white mucosal turbidity, irregular Z-line, horizontal erosions, and mucosal protrusion of cardia were significantly more common in the NERD group compared to controls. Among them, only white mucosal turbidity was independently associated with the NERD group (OR 3.97, 95% CI 1.72-9.13). Individuals with male gender, reflux symptoms, higher height, current smoking, ethanol intake and hiatal hernia were more likely to have white mucosal turbidity compared to the group without white turbidity. CONCLUSIONS: MC could be a useful marker to support clinical diagnosis of GERD. White mucosal turbidity in particular might be a GERD-specific sign related to acid-induced mucosal damage.

Can rebamipide and proton pump inhibitor combination therapy promote the healing of endoscopic submucosal dissection-induced ulcers? A randomized, prospective, multicenter study.

BACKGROUND: There has been no consensus regarding the optimal treatment durations and drug regimens in patients with endoscopic submucosal dissection (ESD)-induced ulcers. OBJECTIVE: To assess the efficacy of proton pump inhibitor (PPI) and rebamipide combination therapy compared with PPI monotherapy for ESD-induced ulcer healing. DESIGN: Randomized, prospective, controlled study; clinical trial. SETTING: Five hospitals in a University Medical Center group in Korea. PATIENTS: This study involved 290 adults (309 lesions) who underwent ESD for gastric adenoma or early gastric cancer. INTERVENTION: PPI and rebamipide combination therapy. MAIN OUTCOME MEASUREMENTS: The ulcer healing rate at 4 weeks after ESD. RESULTS: The ulcer healing rates at 4 weeks after ESD in the PPI and rebamipide combination therapy group were significantly higher than those in the PPI alone group, both in the full analysis (94.9% vs 89.9%; P < .0001) and in the per-protocol analysis (94.5% vs 91.2%; P = .020). This combination therapy was an independent predictive factor for a high ulcer healing rate (adjusted odds ratio [OR] 5.572; 95% confidence interval [CI], 2.615-11.876; P = .014). Additionally, the combination therapy group exhibited a higher quality of ulcer healing than the PPI monotherapy group (reviewer 1: P = .027; OR 1.949; 95% CI, 1.077-3.527; reviewer 2: P = .027; OR 1.933; 95% CI, 1.074-3.481). LIMITATIONS: Open-label study. CONCLUSION: PPI and rebamipide combination therapy had a superior 4-week ESD-induced ulcer healing rate and quality of ulcer healing compared with PPI monotherapy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01167101.).