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Introduction Leakage is a serious and potentially fatal complication of gastrectomy for gastric cancer. However, comprehensive reports regarding leakage after gastrectomy remain limited. We aimed to evaluate the incidence and treatment outcomes of leakage after gastrectomy for cancer. Methods We reviewed the prospectively collected data of 14,075 Patients who underwent gastrectomy for gastric cancer between 2005 and 2017. Outcomes included incidence, risk factors of leakage, and leakage treatment outcomes. Results The median day of leakage detection was postoperative day 7 (range 1–29days). The overall leakage incidence was 1.51% (213/14,075), and the most frequent location was the oesophagojejunostomy (2.07%). Leakage after total gastrectomy was more frequent with minimally invasive surgery (open:1.64%, laparoscopic:3.56%, robotic:5.83%; P Conclusions Leakage after gastric cancer surgery is associated with high mortality. Improved surgeon experience using minimally invasive techniques is required to reduce the risk of leakage. Surgery is an effective treatment for early leakage, although further studies are needed to establish the most appropriate treatment strategies.

BACKGROUND AND PURPOSE: Accurate assessment of thyroid cartilage invasion on preoperative imaging influences management in patients with laryngeal and hypopharyngeal cancers. We evaluated the clinical usefulness of contrast-enhanced 3D T1-weighted radial gradient recalled-echo for preoperative assessment of thyroid cartilage invasion in patients with laryngohypopharyngeal squamous cell carcinoma, compared with 2D spin-echo T1WI. MATERIALS AND METHODS: Preoperative MR images of 52 consecutive patients who were diagnosed with laryngeal or hypopharyngeal cancer and underwent partial or total laryngectomy were analyzed. Pathologic specimens served as reference standards. Two independent head and neck radiologists evaluated the presence of thyroid cartilage invasion in both contrast-enhanced 2D spin-echo T1WI and 3D gradient recalled-echo sequences. The sensitivity, specificity, and accuracy of the 2 modalities were compared. The area under the curve was a measure of diagnostic performance. RESULTS: Pathologic neoplastic thyroid cartilage invasion was identified in 24 (46.2%) of the 52 patients. The sensitivity (75.0%), specificity (96.4%), and accuracy (86.5%) of contrast-enhanced 3D gradient recalled-echo were significantly higher than those of 2D spin-echo T1WI (58.3%, 89.3%, and 75.0%; P = .017, .003, and .002, respectively). 3D gradient recalled-echo had significantly better diagnostic performance (area under the curve = 0.963) than 2D spin-echo T1WI (area under the curve = 0.862; P = .010). CONCLUSIONS: Contrast-enhanced 3D gradient recalled-echo was diagnostically superior in identifying neoplastic thyroid cartilage invasion compared with 2D spin-echo T1WI in patients with laryngohypopharyngeal cancer, and therefore, may provide more accurate preoperative staging.

BACKGROUND AND PURPOSE: Differentiating glioblastoma from solitary brain metastasis preoperatively using conventional MR images is challenging. Deep learning models have shown promise in performing classification tasks. The diagnostic performance of a deep learning–based model in discriminating glioblastoma from solitary brain metastasis using preoperative conventional MR images was evaluated. MATERIALS AND METHODS: Records of 598 patients with histologically confirmed glioblastoma or solitary brain metastasis at our institution between February 2006 and December 2017 were retrospectively reviewed. Preoperative contrast-enhanced T1WI and T2WI were preprocessed and roughly segmented with rectangular regions of interest. A deep neural network was trained and validated using MR images from 498 patients. The MR images of the remaining 100 were used as an internal test set. An additional 143 patients from another tertiary hospital were used as an external test set. The classifications of ResNet-50 and 2 neuroradiologists were compared for their accuracy, precision, recall, F1 score, and area under the curve. RESULTS: The areas under the curve of ResNet-50 were 0.889 and 0.835 in the internal and external test sets, respectively. The area under the curve of neuroradiologists 1 and 2 were 0.889 and 0.768 in the internal test set and 0.857 and 0.708 in the external test set, respectively. CONCLUSIONS: A deep learning–based model may be a supportive tool for preoperative discrimination between glioblastoma and solitary brain metastasis using conventional MR images.

BACKGROUND AND PURPOSE: Isocitrate dehydrogenase (IDH) wild-type lower-grade gliomas (histologic grades II and III) with epidermal growth factor receptor (EGFR) amplification or telomerase reverse transcriptase (TERT) promoter mutation are reported to behave similar to glioblastoma. We aimed to evaluate whether MR imaging features could identify a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma. MATERIALS AND METHODS: In this multi-institutional retrospective study, pathologically confirmed IDH wild-type lower-grade gliomas from 2 tertiary institutions and The Cancer Genome Atlas constituted the training set (institution 1 and The Cancer Genome Atlas, 64 patients) and the independent test set (institution 2, 57 patients). Preoperative MRIs were analyzed using the Visually AcceSAble Rembrandt Images and radiomics. The molecular glioblastoma status was determined on the basis of the presence of EGFR amplification and TERT promoter mutation. Molecular glioblastoma was present in 73.4% and 56.1% in the training and test sets, respectively. Models using clinical, Visually AcceSAble Rembrandt Images, and radiomic features were built to predict the molecular glioblastoma status in the training set; then they were validated in the test set. RESULTS: In the test set, a model using both Visually AcceSAble Rembrandt Images and radiomic features showed superior predictive performance (area under the curve = 0.854) than that with only clinical features or Visually AcceSAble Rembrandt Images (areas under the curve = 0.514 and 0.648, respectively; P CONCLUSIONS: MR imaging features integrated with machine learning classifiers may predict a subset of IDH wild-type lower-grade gliomas that carry molecular features of glioblastoma.

Background/Aims: Endoscopic vacuum-assisted closure (EVAC) has been attempted as new nonsurgical treatment for anastomotic leakage. We aimed to evaluate the clinical outcomes of EVAC and compare its efficacy with the self-expandable metallic stent (SEMS) for postgastrectomy leakage. Methods: Between January 2007 and February 2018, 39 patients underwent endoscopic treatment for anastomotic leakage after gastric cancer surgery. Of them, 28 patients were treated with SEMS, seven with EVAC after SEMS failure, and four with EVAC. We retrospectively compared the clinical characteristics and therapeutic outcomes between EVAC (n=11) and SEMS (n=28). Results: The median follow-up duration was 17 months (interquartile range, 9 to 26 months) in both groups. In comparison of clinical characteristics between two groups, only the median size of the leak was larger in the EVAC group than in the SEMS group (2.1 cm vs 1.0 cm; p

Objectives The increasing prevalence of multidrug-resistant microorganisms (MDRO) is increasing the frequency of poor clinical outcomes, prolonging hospitalizations, and raising healthcare costs. This study evaluated the eradication efficacy of fecal microbiota transplantation (FMT) and identified microbial and functional biomarkers of MDRO decolonization. Methods Fecal solution obtained from healthy unrelated donors was infused in the participants’ guts which had been colonized with carbapenemase-producing enterobacteriacea (CPE), vancomycin-resistant enterococci (VRE), or both CPE and VRE. Fecal samples from recipients were collected and microbiome changes before and after FMT were assessed. Results Twenty-four (68.6%) out of 35 patients were decolonized within one year of receiving FMT. Multivariate analysis showed that FMT (FMT: hazard ratio (HR) = 5.343, 95% confidence interval (CI) = 1.877-15.212, p = 0.002) and MDRO types (CPE: HR = 11.146, 95% CI = 2.420-51.340, p = 0.002; CPE/VRE: HR = 2.948, 95% CI = 1.200-7.246, p = 0.018; VRE served as the reference) were significant independent factors associated with time to decolonization. Microbiota analysis showed higher richness and biodiversity before FMT resulted in VRE decolonization. The species Clostridium ramosum and the genuses Anaerostipes and Eisenbergiella could serve as taxonomic biomarkers and K02017 could serve as a functional biomarker for VRE clearance. Conclusion FMT is an effective way to decolonize MDRO and its effectiveness may be predicted by microbiome analysis.

Endoscopic submucosal dissection (ESD) has a favorable outcome, compared to esophagectomy, for early esophageal neoplasia. Recent studies used general anesthesia for esophageal ESD to minimize complications due to insufficient sedation and patient movement. We aimed to evaluate the safety of general anesthesia in comparison with conscious sedation provided by anesthesiologists for esophageal ESD. We retrospectively reviewed the electronic medical records of 158 patients who underwent esophageal ESD under general anesthesia or conscious sedation provided by anesthesiologists. We evaluated the incidence of procedure-related complications, including perforation, post-ESD bleeding, cardiopulmonary adverse events (arrhythmia, hypotension, and hypoxemia), procedure failure, stricture, and new lung consolidation after ESD. Cases of frank perforation, post-ESD bleeding requiring a vigorous diagnostic approach, and cardiopulmonary adverse events were regarded as acute complications of ESD. Acute complications occurred only in the conscious sedation group (8/83 [9.6%] vs. 0/75 [0.0%]; p value = 0.007). The numbers of patients with frank perforation, post-ESD bleeding, and cardiopulmonary adverse events were four, one, and three, respectively. Moreover, new lung consolidation after ESD developed only in the conscious sedation group (7/83 [8.4%] vs. 0/75 [0.0%]; p value = 0.014). ESD failed in four patients in the conscious sedation group. The incidences of stricture that required stent insertion and hospital stay after ESD were comparable between the two groups. General anesthesia is associated with a lower incidence of acute procedure-related complications in esophageal ESD compared to conscious sedation provided by anesthesiologists. Therefore, we recommend general anesthesia as a safer option for esophageal ESD.

Studies that investigated esophageal microbiomes are limited when compared to those on intestinal microbiomes. Nevertheless, several studies have investigated the relationship between esophageal microbiomes and various esophageal diseases, owing to the advancement of next-generation sequencing techniques. Streptococcus is the most common bacterial taxon in a normal esophagus. Additionally, Haemophilus, Neisseria, Prevotella, and Veillonella are also found. However, gram-negative bacteria, including Prevotella, are more abundant in a diseased esophagus, such as in gastroesophageal reflux disease and Barrett’s esophagus. This systematic review aims to summarize current evidences on esophageal microbiomes in various esophageal diseases. (J Neurogastroenterol Motil 2020;26:171-179)

Supplemental Digital Content is available in the text., Goals: We assessed the efficacy of polaprezinc plus proton pump inhibitor (PPI) treatment for endoscopic submucosal dissection (ESD)-induced ulcer healing compared with rebamipide plus PPI treatment. Background: ESD has been widely used as a local treatment option that cures gastric neoplasms. However, it causes large and deep artificial ulcers, and there are no guidelines with regard to the optimal treatment durations and drug regimens for ESD-induced ulcers. Polaprezinc is effective for promoting ulcer healing and helps enhance the quality of ulcer healing. Study: Two hundred ten patients with ESD-induced ulcers were randomly allocated to treatment with polaprezinc (150 mg/d) plus pantoprazole (40 mg/d) or treatment with rebamipide (300 mg/d) plus pantoprazole (40 mg/d). We evaluated the ulcer healing rate and condition of the ulcer at 4 weeks after dissection. The χ2 or Fisher exact test and the Student t test were used. Results: The ulcer healing rates at 4 weeks after dissection in the polaprezinc plus pantoprazole treatment group were not inferior compared with those in the rebamipide plus pantoprazole treatment group, both in the intention-to-treat analysis (90.3% and 91.4%, respectively, P=0.523) and per-protocol analysis (89.9% and 91.1%, respectively, P=0.531). The short procedure time was an independent predictive factor for a high ulcer healing rate (odds ratio: 0.975; 95% confidence interval: 0.958-0.993; P=0.006). Conclusion: The polaprezinc plus PPI treatment showed noninferiority to rebamipide plus PPI treatment in the ulcer healing rate at 4 weeks after ESD.

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. 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. 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

BackgroundThe number of elderly patients with superficial esophageal cancer (SEC) is increasing. We aimed to evaluate the clinical outcomes and prognostic factors of overall survival (OS) in elderly patients undergoing endoscopic submucosal dissection (ESD) or surgical resection for SEC.MethodsBetween January 2001 and May 2020, 290 patients aged ≥65 years who underwent ESD or surgical resection for SEC were evaluated. Their clinical outcomes and prognosis were assessed, and independent risk factors for OS were identified.ResultsThe mean patient age (269 men and 21 women) was 70.9 years (range 65–90 years). En bloc, R0, and curative resections were achieved in 94.5%, 90.0%, and 73.4% of the patients, respectively. During the follow-up [mean: 54.6 months (range: 1–210 months)], 79 patients died. The 3-, 5-, and 10-year OS rates were 82.5, 73.1, and 59.7%, respectively. In multivariate analysis, cancer history of the other organs, American Society of Anesthesiologists performance status, and presence of lymphovascular involvement (hazard ratio = 1.852, 1.656, and 1.943, respectively; all P < 0.05) were independent risk factors for poor OS. The high-risk group (≥2 risk factors) showed a significantly lower OS than the low-risk group (≤ 1 risk factor) (P < 0.001).ConclusionsThe three risk factors could be useful in predicting the long-term prognosis of elderly patients with SEC.

BACKGROUND AND PURPOSE: The detection of cerebral aneurysms on MRA is a challenging task. Recent studies have used deep learning–based software for automated detection of aneurysms on MRA and have reported high performance. The purpose of this study was to evaluate the incremental value of using deep learning–based software for the detection of aneurysms on MRA by 2 radiologists, a neurosurgeon, and a neurologist. MATERIALS AND METHODS: TOF-MRA examinations of intracranial aneurysms were retrospectively extracted. Four physicians interpreted the MRA blindly. After a washout period, they interpreted MRA again using the software. Sensitivity and specificity per patient, sensitivity per lesion, and the number of false-positives per case were measured. Diagnostic performances, including subgroup analysis of lesions, were compared. Logistic regression with a generalized estimating equation was used. RESULTS: A total of 332 patients were evaluated; 135 patients had positive findings with 169 lesions. With software assistance, patient-based sensitivity was statistically improved after the washout period (73.5% versus 86.5%, P < .001). The neurosurgeon and neurologist showed a significant increase in patient-based sensitivity with software assistance (74.8% versus 85.2%, P = .03, and 56.3% versus 84.4%, P < .001, respectively), while the number of false-positive cases did not increase significantly (23 versus 30, P = .20, and 22 versus 24, P = .75, respectively). CONCLUSIONS: Software-aided reading showed significant incremental value in the sensitivity of clinicians in the detection of aneurysms on MRA without a significant increase in false-positive findings, especially for the neurosurgeon and neurologist. Software-aided reading showed equivocal value for the radiologist.

Background/Aims: Bicarbonate-containing alginate formula tions are reported to be effective for controlling reflux symp toms. However, the efficacy of Lamina G alginate without gas production has not been reported. The aim is to evaluate the efficacy of a non-bicarbonate alginate in individuals with reflux symptoms without reflux esophagitis. Methods: Par ticipants who had experienced heartburn or regurgitation for 7 consecutive days were randomized to one of the following treatment groups: proton pump inhibitors (PPI) plus alginate (combination) or PPI plus placebo (PPI only). In addition, as a reference group, patients received placebo plus alginate (alginate only). The primary endpoint compared the percent age of patients with complete resolution of symptoms for the final 7 days of the treatment. Secondary endpoints com pared changes in symptom score, symptom-free days during the treatment period, the Reflux Disease Questionnaire, Pa tient Assessment of Upper Gastrointestinal Disorders (PAGI)-Quality of Life and PAGI-Symptoms Severity Index scores, the investigator’s assessment of symptoms, and incidence of ad verse events. Results: Complete resolution of heartburn or regurgitation was not significantly different between the com bination and PPI only groups (58.7% vs 57.5%, p=0.903). The secondary endpoints were not significantly different between the two groups. Complete resolution of heartburn or regurgitation, did not differ between the alginate only reference group and the PPI only group (75.0% vs 57.5%, p=0.146). Conclusions: The addition of non-bicarbonate al ginate to PPI was no more effective than PPI alone in control ling reflux symptoms. (Gut Liver 2019;13:642-648)

Background and purpose To evaluate the safety and efficacy of preoperative chemotherapy (CTx) followed by chemoradiotherapy (CCRT) for high-risk gastric cancer (GC). Methods and materials The inclusion criteria were as follows: (1) Borrmann type 4; (2) large Borrmann type 3 (≥8 cm); (3) single bulky (≥3 cm × 1) or multiple lymph nodes (≥1.5 cm × 3). Patients received two 21-day courses of induction CTx of TS-1 (35 mg/m2, p.o, twice daily on days 1–14), docetaxel (30 mg/m2, i.v., days 1 and 8), and cisplatin (30 mg/m2, i.v., days 1 and 8) followed by CCRT (two courses of TS-1 and cisplatin in combination with 45 Gy radiation). Results Forty-two patients were enrolled between March 2014 and February 2016, and 39 of these completed sequential CTx and CCRT. Among the 33 patients who underwent R0 resection, the pathologic response rate was 39.4% [no residual carcinoma (n = 5, 15.2%), with 1–10% residual carcinoma (n = 8, 24.2%)]. Overall, 4 patients (12.1%) were pathologic stage 0, 7 (21.2%) were stage I, 10 (30.3%) were stage II, and 12 (36.4%) were stage III. The overall survival rate at 3 years was 77.9% for stages 0 and I, 66.8% for stages II–III, and 33.3% for unresectable cases (P = 0.001). Toxicity was mild to moderate with grade 4 neutropenia (n = 1) and neutropenic fever (n = 1) as the most prominent side-effects. Conclusions Sequential CTx and CCRT prior to surgery are feasible and effective for high-risk GC. Trial registration number: NCT02495493.

Subepithelial tumors (SETs) are difficult to diagnose accurately without invasive pathological confirmation. We created a noninvasive prediction model for diagnosing gastrointestinal stromal tumors (GISTs) using contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS).We retrospectively reviewed 176 patients who underwent CEH-EUS from October 2011 to August 2017. Seventy patients with a diagnosis of GIST (n = 37) or leiomyoma (n = 33) were included. The long-to-short axis ratio (LSR) and enhancement patterns (vascularity, diffuse enhancement) on CEH-EUS were assessed. Logistic regression and classification and regression tree (CART) analyses were performed.The mean age of all patients was 54.9 ± 13.68 years. The GIST group showed significantly higher rates of positive vascularity (81.1% vs. 15.2%, p 0.001) and diffuse enhancement (51.4% vs. 15.2%, p = 0.001), and lower LSR (1.30 vs. 1.76, p 0.001). In multivariate logistic regression, positive vascularity (odds ratio [OR] 27.765, 95% confidence interval [CI] 5.336-144.458) and low LSR (OR 18.940, 95% CI 3.623-99.007) were independent predictors of GIST. A noninvasive prediction model for GISTs was developed using the CART model, by allocating patients according to statistically significant variables.The LSR and vascularity of SETs on CEH-EUS can be used as parameters for a noninvasive prediction model of GISTs. This model may be helpful in the early identification and treatment of GISTs.

Background/Aims: Endoscopic resection is a standard treatment for stage T1a esophageal cancer, with esophagectomy or radical radiation therapy (RT) performed for stage T1b lesions. This study aimed to compare treatment outcomes of each modality for clinical stage T1 esophageal cancer. Methods: In total, 179 patients with clinical T1N0M0- stage esophageal cancer treated from 2006 to 2016 were retrospectively evaluated. Sixty-two patients with clinical T1a-stage cancer underwent endoscopic resection. Among 117 patients with clinical T1b-stage cancer, 82 underwent esoph-agectomy, and 35 received chemoradiotherapy or RT. We compared overall survival (OS) and recurrence-free survival (RFS) rates for each treatment modality. Results: The median follow-up time was 32 months (range, 1 to 120 months). The 5-year OS and RFS rates for patients with stage T1a cancer receiving endoscopic resection were 100% and 85%, respectively. For patients with stage T1b, the 5-year OS and RFS rates were 78% and 77%, respectively, for the esophagectomy group; 80% and 44%, respectively, for the RT alone group; and 96% and 80%, respectively, for the chemoradiation group. The esophagectomy group showed significantly higher RFS than the RT alone group (p=0.04). There was no significant difference in RFS between the esophagectomy and chemoradiation groups (p=0.922). Grade 4 or higher treatment-related complications occurred in four patients who underwent esophagectomy. Conclusions: Endoscopic resection appeared to be an adequate treatment for patients with T1a-stage esophageal cancer. The multidisciplinary approach involving chemoradiation was comparable to esophagectomy in terms of survival outcome without serious complications for T1b-stage esophageal cancer. (Gut Liver 2019;13:315-324)

Background/Aims: Gastric cancer is one of the most common malignant tumors worldwide with poor prognosis due to a lack of effective treatment modalities. Recent research showed that a long noncoding RNA named N-BLR modulates the epithelial-to-mesenchymal transition (EMT) process in colorectal cancer. However, the biological role of N-BLR in gastric cancer still remains to be explored. The aim of this study was to investigate the possibility of N-BLR as an EMT modulator in gastric cancer. Methods: The expression of N-BLR was measured by quantitative polymerase chain reaction in fresh gastric cancer tissue, paired adjacent normal tissues and cell lines. Fresh gastric tissues, paired samples obtained by surgery and clinical data were collected prospectively. Knockdown of N-BLR was induced by small interfering RNA (siRNAs). Cell number and viability were assessed after treatment with siRNAs. The ability of N-BLR to promote metastasis was measured using migration and invasion assays. Additionally, an inverse correlation between N-BLR and miR-200c was measured by TaqMan microRNA assays. Western blotting was performed to detect EMT and apoptosis markers upon knockdown of N-BLR. Results: N-BLR expression was significantly elevated in gastric cancer cell lines and tissues compared to that in a normal gastric cell line and adjacent normal tissues (p

Background/aims Recently, increased body weight has been found to be associated with an increasing risk of several cancers, including gastric cancer. The true pathogenic role of hyperglycemia in the development of gastric cancer remains unclear as hyperglycemia and its associated conditions may work as carcinogenic factors. The goal of this study was to clarify the factors associated with early gastric cancer and evaluate a homeostasis model assessment of the insulin resistance (HOMA-IR) index, fasting glucose, and lipid profile as predictors of early gastric cancer. Methods A total of 63 patients with early gastric cancer between November 2012 and March 2013 were included. Preoperative serum lipid profile levels and serum fasting glucose were examined prospectively in patients with early gastric cancer. The same number of controls were evaluated and matched to the early gastric cancer group for age and gender. We performed multivariate logistic regression analysis to identify independent risk factors for early gastric cancer. Results Univariate analysis showed that risk for early gastric cancer was associated with diastolic blood pressure (BP), total cholesterol, fasting glucose, and HOMA-IR. In the multivariate-adjusted model, higher total cholesterol, fasting glucose, body mass index, and diastolic BP were strongly associated with an increased risk of early gastric cancer. Conclusions Hyperglycemia, a lower high-density lipoprotein cholesterol level, and a low HOMA-IR level appear to be associated with early gastric cancer risk.

MINI: A risk-scoring system for predicting extragastric recurrence after surgical resection of early gastric cancer was developed. The low-risk group showed an extremely rare extragastirc recurrence and higher extragastric recurrence-free survival than the high-risk group. Postsurgical computed tomography surveillance may be unnecessary in the low-risk group after curative resection of early gastric cancer. OBJECTIVE To stratify the postsurgical computed tomography (CT) surveillance based on a risk-scoring system for predicting extragastric recurrence after surgical resection of early gastric cancer (EGC). SUMMARY OF BACKGROUND DATA Postsurgical CT surveillance should not be routinely performed in all patients because of the low incidence of extragastric recurrence and potential risk of radiation exposure. METHODS Data from 3162 patients who underwent surgical resection for EGC were reviewed to develop a risk-scoring system to predict extragastric recurrence. Risk scores were based on the predictive factors for extragastric recurrence, which were determined using Cox proportional hazard regression model. The risk-scoring system was validated by Uno censoring adjusted C-index. External validation was performed using an independent dataset (n = 430). RESULTS The overall incidence of extragastric recurrence was 1.4% (44/3162). Five risk factors (lymph node metastasis, indications for endoscopic resection, male sex, positive lymphovascular invasion, and elevated macroscopic type), which were significantly associated with extragastric recurrence, were incorporated into the risk-scoring system, and the patients were categorized into 2 risk groups. The 10-year extragastric recurrence-free survival differed significantly between low- and high-risk groups (99.7% vs 96.5%; P < 0.001). The predictive accuracy of the risk-scoring system in the development cohort was 0.870 [Uno C-index; 95% confidence interval (95% CI), 0.800-0.939]. Discrimination was good after internal (0.859) and external validation (0.782, 0.549-1.000). CONCLUSION This risk-scoring system might be useful to predict extragastric recurrence of EGC after curative surgical resection. We suggest that postsurgical CT surveillance to detect extragastric recurrence should be avoided in the low-risk group.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the "proven GERD" with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

BACKGROUND AND AIM Bleeding after endoscopic submucosal dissection (ESD) is a main adverse event. To date, although there have been several studies about risk factors for post-ESD bleeding, there has been few predictive model for post-ESD bleeding with large volume cases. We aimed to design a prediction model for post-ESD bleeding using a classification tree model. METHODS We analyzed a prospectively established cohort of patients with gastric neoplasms treated with ESD from 2007 to 2016. Baseline characteristics were collected for a total of 5080 patients, and the bleeding risk was estimated using variable statistical methods such as logistic regression, AdaBoost, and random forest. To investigate how bleeding was affected by independent predictors, the classification and regression tree (CART) method was used. The prediction tree developed for the cohort was internally validated. RESULTS Post-ESD bleeding occurred in 262 of 5080 patients (5.1%). In multivariate logistic regression, ongoing antithrombotic use during the procedure, cancer pathology, and piecemeal resection were significant risk factors for post-ESD bleeding. In the CART model, the decisive variables were ongoing antithrombotic agent use, resected specimen size ≥49 mm, and patient age

Non-erosive reflux disease (NERD) pathogenesis has not been thoroughly evaluated. Here, we assessed the response of patients with NERD to proton pump inhibitor (PPI) therapy; changes in the microbiome and biologic marker expression in the esophageal mucosa were also evaluated. Patients with NERD (n = 55) received esomeprazole (20 mg) for eight weeks. The treatment response was evaluated at baseline, week four, and week eight. Esophageal mucosal markers and oropharyngeal and esophageal microbiomes were analyzed in patients who underwent upper gastrointestinal endoscopy at screening (n = 18). Complete and partial response rates at week eight were 60.0% and 32.7% for heartburn, and 61.8% and 29.1% for regurgitation, respectively. The expressions of several inflammatory cytokines, including IL-6, IL-8, and NF-κB, were decreased at week eight. Streptococcus, Haemophilus, Prevotella, Veillonella, Neisseria, and Granulicatella were prevalent regardless of the time-point (baseline vs. week eight) and organ (oropharynx vs. esophagus). The overall composition of oropharyngeal and esophageal microbiomes showed significant difference (P = 0.004), which disappeared after PPI therapy. In conclusion, half-dose PPI therapy for eight weeks could effectively control NERD symptoms. The expression of several inflammatory cytokines was reduced in the esophagus, and oropharyngeal and esophageal microbiomes in patients with NERD showed significant difference. However, the microbial compositions in the oropharynx and esophagus were not affected by PPI therapy in this study. Impact of PPI on the microbiome in patients with NERD should be more investigated in future studies.

ObjectiveTo investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target.DesignFLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA. We further explored the therapeutic potential of targeting FLANC in a mouse model of colorectal cancer (CRC) metastases.ResultsFLANC, a primate-specific lncRNA feebly expressed in normal colon cells, was significantly upregulated in cancer cells compared with normal colon samples in two independent cohorts. High levels of FLANC were associated with poor survival in two additional independent CRC patient cohorts. Both in vitro and in vivo experiments demonstrated that the modulation of FLANC expression influenced cellular growth, apoptosis, migration, angiogenesis and metastases formation ability of CRC cells. In vivo pharmacological targeting of FLANC by administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with a specific small interfering RNA, induced significant decrease in metastases, without evident tissue toxicity or pro-inflammatory effects. Mechanistically, FLANC upregulated and prolonged the half-life of phosphorylated STAT3, inducing the overexpression of VEGFA, a key regulator of angiogenesis.ConclusionsBased on our findings, we discovered, FLANC as a novel primate-specific lncRNA that is highly upregulated in CRC cells and regulates metastases formation. Targeting primate-specific transcripts such as FLANC may represent a novel and low toxic therapeutic strategy for the treatment of patients.

Background and aim A high yield of biopsy is mandatory to perform molecular genetic research with endoscopically obtained gastric cancer tissues. We evaluated whether probe-based confocal laser endomicroscopy (pCLE) can increase the yield of endoscopic biopsy for gastric cancer compared with white light endoscopy (WLE). Methods All lesions in the pCLE and WLE groups were initially evaluated through WLE. In the pCLE group, lesions were further examined through pCLE. In the pilot study, five and three biopsy specimens were obtained for histopathological examination and tumor marker analysis, respectively. In the confirmatory study, six biopsy specimens for histopathological evaluation were obtained. Results A total of 30 gastric cancers and 61 undifferentiated-type gastric cancers were analyzed in the pilot and confirmatory studies, respectively. The proportion of cancer cells in biopsy samples of poorly differentiated adenocarcinoma or signet ring cell carcinoma was higher in the pCLE group than in the WLE group in both the pilot and confirmatory studies (pilot: median proportion, 65% vs 30%, P = 0.010; confirmatory: mean ± standard deviation, 49.5 ± 29.3 vs 29.3 ± 13.7, P = 0.002). The expression ratio of tumor markers including carcinoembryonic antigen, GW112, HOX transcript antisense RNA, and H19 tended to be higher in the pCLE group than in the WLE group. Conclusion Probe-based confocal laser endomicroscopy-targeted biopsy provided superior results in terms of the proportion of cancer cells in biopsy samples compared with WLE-targeted biopsy in gastric cancer with undifferentiated histology.

PURPOSE Patients with gastroesophageal reflux disease without esophagitis show varying responses to proton pump inhibitors (PPIs). The aim of this study was to objectively evaluate the effect of a new PPI, ilaprazole, on patients with heartburn but without reflux esophagitis. MATERIALS AND METHODS This prospective study was performed on 20 patients with heartburn but without reflux esophagitis. All patients underwent upper endoscopy and 24-hr combined multichannel intraluminal impedance and pH esophageal monitoring (MII-pH). They were then treated with ilaprazole (20 mg) once daily for 4 weeks. The GerdQ questionnaire, histologic findings, and inflammatory biomarkers were used for assessment before and after ilaprazole. RESULTS Among the 20 patients, 13 (65%) showed GerdQ score ≥8. Based on MII-pH results, patients were classified as true nonerosive reflux disease (n=2), hypersensitive esophagus (n=10), and functional heartburn (n=8). After treatment, patients showed a statistically significant improvement in GerdQ score (p

Background and aim Recently, the application of hemostatic powder to the bleeding site has been used to treat active upper gastrointestinal bleeding (UGIB). We aimed to assess the effectiveness of the polysaccharide hemostatic powder (PHP) in patients with non-variceal UGIB. Methods We reviewed prospectively collected 40 patients with UGIB treated with PHP therapy between April 2016 and January 2017 (PHP group) and 303 patients with UGIB treated with conventional therapy between April 2012 and October 2014 (conventional therapy group). We compared the rate of successful hemostasis and the rebleeding between the two groups after as well as before propensity score matching using the Glasgow-Blatchford score and Forrest classification. Results Thirty patients treated with the PHP and 60 patients treated with conventional therapy were included in the matched groups. Baseline patient characteristics including comorbidities, vital signs, and bleeding scores were similar in the matched groups. The rate of immediate hemostasis and 7-day and 30-day rebleeding were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate hemostasis or rebleeding rate were noted between PHP in monotherapy and PHP combined with a conventional hemostatic method. At 30 days after the therapy, there were no significant PHP-related complications or mortality. Conclusions Given its safety, the PHP proved feasible for endoscopic treatment of UGIB, having similar effectiveness as that of conventional therapy. The PHP may become a promising hemostatic method for non-variceal UGIB.

The aim of this study was to analyze long-term clinical and oncologic outcomes in patients with early-stage adenocarcinoma of the esophagogastric junction (AEG) managed with either endoscopic resection (ER) or surgery. The inclusion criteria were AEG, meeting classic or expanded indications for ER of early gastric cancer, and complete resection. A total of 66 patients with Siewert type II AEG were included (ER group, n = 38; vs. surgery group, n = 28). The mean age of the ER group was greater than that of the surgery group (mean ± SD, 66.9 ± 9.7 vs. 58.5 ± 10.4 years, respectively; p = 0.001). Compared to the ER group, macroscopically flat or depressed-type lesions were more common (47.4 vs. 89.3%; p = 0.001), and mean lesion size was larger in the surgery group (13.3 ± 8.4 vs. 18.6 ± 11.0 mm; p = 0.039). One intensive care unit admission and subsequent surgery-related death occurred in the surgery group (1/28 vs. 0/38 in the ER group; p = 0.424). During follow-up, recurrence was detected in both groups (4/38 vs. 1/28; p = 0.385). Overall survival and 5-year disease-free survival did not differ between the groups (93.3 vs. 92.9%; p = 0.282 and 88.0 vs. 100.0%; p = 0.066). Once complete resection is achieved in patients with AEG who met the expanded criteria for endoscopic submucosal dissection of gastric cancer, there was no significant difference in clinical outcomes between ER and surgery.

Background Although propofol has been widely used for sedation during esophagogastroduodenoscopy (EGD), adverse events including hypoxia and hypotension may be a concern in the propofol-based sedation. We aimed to analyze whether administration of midazolam would improve safety and efficacy of propofol-based sedation in EGD. Methods One hundred twenty patients who were scheduled to undergo diagnostic EGD were randomly assigned to either midazolam plus propofol (MP) or propofol alone groups. In the MP group, 2mg of midazolam and 10mg of propofol were given initially. In the propofol alone group, 40-60mg of propofol was given initially. In both groups, 20mg of propofol was given repeatedly to maintain moderate sedation as needed. Vital signs including oxygen saturation were monitored every 2 minutes. After the patients fully recovered, satisfaction score was investigated from endoscopists, nurses and patients, respectively. Results The baseline characteristics did not differ between the MP and propofol alone groups. The mean required doses of propofol was (mean±standard deviation) 0.3±0.3 mg/kg and 0.8±0.2 mg/kg in the MP and propofol alone groups, respectively (P 0.999; endoscopist, 73.3% vs. 80.0%, P=0.064; nurse, 73.3% vs. 76.7%, P=0.551). Conclusion Adding midazolam to propofol did not reduced the safety and efficacy, sedation using propofol alone could be suitable for sedation during diagnostic EGD.

Background/aims Colonoscopic surveillance is currently recommended after polypectomy owing to the risk of newly developed colonic neoplasia. However, few studies have investigated colonoscopy surveillance in Asia. This multicenter and prospective study was undertaken to assess the incidence of advanced adenoma based on baseline adenoma findings at 3 years after colonoscopic polypectomy. Methods A total of 1,323 patients undergoing colonoscopic polypectomy were prospectively assigned to 3-year colonoscopy surveillance at 11 tertiary endoscopic centers. Relative risks for advanced adenoma after 3 years were calculated according to baseline adenoma characteristics. Results Among 1,323 patients enrolled, 387 patients (29.3%) were followed up, and the mean follow-up interval was 31.0±9.8 months. The percentage of patients with advanced adenoma on baseline colonoscopy was higher in the surveillance group compared to the non-surveillance group (34.4% vs. 25.7%). Advanced adenoma recurrence was observed in 17 patients (4.4%) at follow-up. The risk of advanced adenoma recurrence was 2 times greater in patients with baseline advanced adenoma than in those with baseline non-advanced adenoma, though the difference was not statistically significant (6.8% [9/133] vs. 3.1% [8/254], P=0.09). Advanced adenoma recurrence was observed only in males and in subjects aged ≥50 years. In contrast, adenoma recurrence was observed in 187 patients (48.3%) at follow-up. Male sex, older age (≥50 years), and multiple adenomas (≥3) at baseline were independent risk factors for adenoma recurrence. Conclusions A colonoscopy surveillance interval of 3 years in patients with baseline advanced adenoma can be considered appropriate.

Purpose Bleeding is one of the most serious complications of advanced gastric cancer (AGC) and is associated with a poor prognosis. This study aimed to evaluate the clinical outcomes of endoscopic hemostasis for bleeding in patients with unresectable AGC. Materials and Methods This study included 106 patients with bleeding associated with gastric cancer who had undergone endoscopic hemostasis between January 2010 and December 2013. Clinical characteristics, treatment outcomes, including rates of successful endoscopic hemostasis and rebleeding, risk factors for rebleeding, and overall survival (OS) were investigated. Results Successful initial hemostasis was achieved in 83% of patients. Rebleeding occurred in 28.3% of patients within 30 days. The median OS after initial hemostasis was lower in patients with rebleeding than in those without rebleeding (2.7 and 3.9 months, respectively, P=0.02). There were no significant differences in disease status and rebleeding rates among patients with partial response or stable disease (n=4), progressive disease (n=64), and first diagnosis of disease (n=38). Univariate and multivariate analyses (P=0.038 and 0.034, respectively) revealed that transfusion of ≥5 units of RBCs was a significant risk factor for rebleeding. Conclusions Despite favorable success rates of endoscopic hemostasis for bleeding associated with gastric cancer, the 30-day rebleeding rate was 28.3% and the median OS was significantly lower in patients with rebleeding than in those without rebleeding. Massive transfusion (≥5 units of RBCs) was the only significant risk factor for rebleeding. Patients with bleeding associated with AGC who have undergone massive transfusion should be observed closely following endoscopic hemostasis. Further research on approaches to reduce rebleeding rate and prevent death is needed.

Background/Aims The adoption of colonoscopy as a primary colorectal cancer (CRC) screening technique has been argued for in Korea, without evidence of patient preferences. This study aimed to investigate patients’ preferences for the primary CRC screening test for the National Cancer Screening Program (NCSP). Methods Between June and August 2016, 414 individuals aged ≥50 years who participated in the NCSP were prospectively invited to complete a questionnaire regarding their preferences for the primary CRC screening test and the reasons for their selection. Results Among the 396 respondents who completed the questionnaire, 124 individuals (31.3%) preferred the fecal immunochemical test (FIT), whereas 272 individuals (68.7%) preferred colonoscopy. Elderly participants preferred the FIT (p

Background/Aims: Few studies have evaluated the effect of Helicobacter pylori infection on the prognosis of patients diagnosed with gastric cancer (GC) after curative surgery. We investigated the association between the H. pylori infection status and clinical outcome after surgery. Methods: We as-sessed the H. pylori status of 314 patients who underwent curative resection for GC. The H. pylori status was examined using a rapid urease test 2 months after resection. Patients were followed for 10 years after surgery. Results: An H. pylori infection was observed in 128 of 314 patients. The median follow-up period was 93.5 months. A Kaplan-Meier analysis indicated that patients with H. pylori had a higher cumula-tive survival rate than those who were negative for H. pylori. Patients with stage II cancer who tested negative for H. py-lori were associated with a poor outcome. In a multivariate analysis, H. pylori-negative status was a significant indepen-dent prognostic factor for poor overall survival. Conclusions: Having a negative H. pylori infection status seems to indicate poor prognosis for patients with GC who have undergone curative resection. Further prospective controlled studies are needed to evaluate the mechanism by which H. pylori af-fects GC patients after curative surgery in Korea. (Gut Liver 2017;11:635-641)

Esophageal squamous cell carcinoma (ESCC) presenting as subepithelial tumor-like growth is a very rare form of the disease. We report a case of primary ESCC with intramural growth, covered with normal esophageal epithelium. The patient was initially referred due to a subepithelial tumor at the mid-esophagus, butendoscopic ultrasonography revealed a heterogeneously hypoechoic mass, which disrupted the structure of the muscularis propria. An endoscopic submucosal dissection was performed for accurate diagnosis, and the lesion was diagnosed histopathologically as moderately differentiated squamous cell carcinoma. Computed tomography revealed an enlarged left upper paratracheal lymph node, which showed increased uptake on positron emission tomography. The patient underwent subtotal esophagectomy with total mediastinal lymphadenectomy and adjuvant chemotherapy. Primary ESCC with intramural growth is extremely rare. For accurate diagnosis, when there is a high index of suspicion, additional investigations such as endoscopic ultrasonography or diagnostic endoscopic submucosal dissection might be needed.

Purpose The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT). Materials and Methods Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013 were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients. Results There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups. Conclusion A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

Oxyntic gland polyp/adenoma is a recently reported rare neoplasm previously called gastric adenocarcinoma of fundic gland type (chief cell predominant type). We report a case of oxyntic gland adenoma curatively treated with endoscopic mucosal resection. On endoscopy, a small, round polypoid lesion was observed in the fundus of the stomach of a 33-year-old man. He underwent endoscopic mucosal resection with a cap for diagnostic and therapeutic purposes, and was diagnosed as having oxyntic gland adenoma with high-grade dysplasia. On immunohistochemical analysis, the tumor was positive for MUC6 and negative for MUC5AC and MUC2. Our case suggests that endoscopic mucosal resection with immunohistochemical analysis might be useful for correctly diagnosing an uncertain lesion suspected as an oxyntic gland adenoma.

Background and Aims Endoscopic submucosal dissection (ESD) is a useful method for complete resection of early gastric cancer (EGC). However, there are still some patients who undergo additional gastrectomy after ESD because of non-curative resection. There is no model that can accurately predict non-curative resection of ESD. We aimed to create a model for predicting non-curative resection of ESD in patients with EGC. Patients and methods We reviewed the medical records, including all gross findings of EGC, of patients who underwent ESD for EGCs. We divided the patients into a non-curative resection group and a curative resection group. The clinicopathologic characteristics were compared between the groups to identify the risk factors for non-curative resection of ESD. We created a scoring system based on logistic regression modeling and bootstrap validation. Results Of 1639 patients who had undergone ESD for EGCs, 272 were identified as being treated non-curatively with ESD. A large tumor size (≥20 mm), tumor location in the upper body of the stomach, the presence of ulcer, fusion of gastric folds, the absence of mucosal nodularity, spontaneous bleeding, and undifferentiated tumor histology were associated with non-curative resection of ESD. Points of risk scores were assigned for these variables based on the β coefficient as follows: tumor size (≥20 mm), 2 points; tumor location in the upper body of the stomach, 1 point; ulcer, 2 points; fusion of gastric folds, 2 points; absence of mucosal nodularity, 1 point; spontaneous bleeding, 1 point; and undifferentiated histology, 2 points. Our risk scoring model showed good discriminatory performance on internal validation (bootstrap-corrected area under the receiver operating characteristic curve, 0.7004; 95% confidence interval, 0.6655-0.7353). Conclusions We developed a validated prediction model that can be used to identify patients who will undergo non-curative resection of ESD. Our prediction model can provide useful information for making decisions about the treatment of EGC before performing ESD.

BACKGROUND AND AIM We evaluated probe-based confocal laser endomicroscopy (pCLE) in the margin delineation of early gastric cancer (EGC) for endoscopic submucosal dissection in comparison with white-light imaging with chromoendoscopy (CE). METHODS We conducted a prospective, randomized controlled study from November 2013 to October 2014 in a tertiary referral hospital. A total of 101 patients scheduled for endoscopic submucosal dissection due to differentiated EGC were randomized into pCLE and CE groups (pCLE 51, CE 50). Markings were made by electrocautery at the proximal and distal tumor margins, as determined by either pCLE or CE. The distance from the marking to the tumor margin was measured in the resected specimen histopathologically and was compared between the two groups by a linear mixed model. RESULTS Among 104 lesions, 80 lesions with 149 markings (pCLE 68, CE 81) were analyzed after excluding undifferentiated EGCs (n = 8) and unidentifiable markings (n = 13). Although the complete resection rate showed no difference between the groups (94.6% vs 93.2%, P = 1.000), the median distance from the marking to the margin was shorter in the pCLE group (1.3 vs 1.8 mm, P = 0.525) and the proportion of the distance

Gastrointestinal (GI) leakage, fistulae, and perforations can be serious and life threatening. There has been a paradigm shift in the management approach of these conditions, from surgical to conservative, including endoscopic management. Here, we report two cases of endoscopic closure of a GI fistula and perforation using polyglycolic acid (PGA) sheets with fibrin glue. The first case is of an anastomotic leak detected after subtotal gastrectomy with gastroduodenostomy. After failed application of endoclips, a PGA sheet was applied, and the fistula was successfully closed. The second case was of a 15-mm large perforated gastric ulcer, which was also successfully closed with a PGA sheet. This is the first case report that PGA sheet was used for the treatment of overt perforation. The outcome of these cases suggest that endoscopic closure using PGA sheets can be considered as a useful alternative for the management of GI leakage, fistulae, and perforations.

EGD plays an important role in diagnosis of gastric cancer. In Korea and Japan, EGD is accepted a major methods for early gastric cancer screening, however its accuracy can be influened by the competency of endoscopist, inspection time and endoscopic instruments. Screening EGD has led to increase the detection of early gastric cancer and improve the oveall survival of gastric cancer patients in these country. Although the clinical impact of EUS for advanced gastric cancer has been qustioned, still EUS is an useful tool for preoperative staging.

Purpose HOX transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA, has been reported to regulate carcinogenesis by epigenetic mechanism in various cancers. Protocadherin 10 (PCDH10) is one of the well-known tumor suppressor genes, and is frequently methylated in gastric cancers (GC). We aimed to investigate the detailed pathway of how HOTAIR contributes to the target gene in gastric carcinogenesis. Materials and Methods We investigated the mechanism of HOTAIR on carcinogenesis and metastasis of GC. Methylation-specific PCR was performed to identify the interaction between HOTAIR and PCDH10. In addition, we investigated the interaction between miR-148b and HOTAIR by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results The expression of HOTAIR was significantly upregulated in GC tissues (p

Background/Aims: In Korea, the nationwide gastric cancer screening program recommends biennial screening for individuals aged 40 years or older by way of either an upper gastrointestinal series or endoscopy. The national endoscopic quality assessment (QA) program began recommending endoscopy in medical institutions in 2009. We aimed to assess the effect, burden, and cost of the QA program from the viewpoint of medical institutions. Methods: We surveyed the staff of institutional endoscopic units via e-mail. Results: Staff members from 67 institutions replied. Most doctors were endoscopic specialists. They responded as to whether the QA program raised awareness for endoscopic quality (93%) or improved endoscopic practice (40%). The percentages of responders who reported improvements in the diagnosis of gastric cancer, the qualifications of endoscopists, the quality of facilities and equipment, endoscopic procedure, and endoscopic reprocessing were 69%, 60%, 66%, 82%, and 75%, respectively. Regarding reprocessing, many staff members reported that they had bought new automated endoscopic preprocessors (3%), used more disinfectants (34%), washed endoscopes longer (28%), reduced the number of endoscopies performed to adhere to reprocessing guidelines (9%), and created their own quality education programs (59%). Many responders said they felt that QA was associated with some degree of burden (48%), especially financial burden caused by purchasing new equipment. Reasonable quality standards (45%) and incentives (38%) were considered important to the success of the QA program. Conclusions: Endoscopic quality has improved after 5 years of the mandatory endoscopic QA program. Clin Endosc 2016;49:542-547

Ideal sedation for endoscopic submucosal dissection (ESD) aims to satisfy both the endoscopist and patient. However, previous studies show that a satisfactory procedure for the endoscopist does not equal higher patient satisfaction. This study attempted to find a sedation protocol that is able to increase patient satisfaction during propofol-based sedation by adding low-dose midazolam as premedication. Seventy-two adult patients were randomly allocated to receive either 0.02 mg/kg midazolam (Midazolam Group) or placebo (Control Group) as premedication before ESD. Sedation was done by targeting Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale of 3 or 4 with continuous propofol infusion and bolus doses of fentanyl. Satisfaction scores of the endoscopists and patients, and whether the patient was willing to receive the same sedation method in the future was assessed. Interim analysis was done after enrollment of 50 % of patients. This study was prematurely terminated when interim analysis showed that patients willing to receive the same sedation method in the future were significantly lower in the Control Group compared to the Midazolam Group (P = 0.001). There was no difference in sedation time, procedure and recovery time, drug requirements and adverse events between the two groups. Endoscopist and overall patient satisfaction scores, patient pain scores and degree of recall were also similar between groups. A small dose of midazolam given as premedication before propofol-based sedation is able to reduce patient reluctance to repeat the same procedure in the future, without affecting procedural performance, recovery time or endoscopist satisfaction.

Gastric “crawling-type” adenocarcinoma (CRA) is a tumor histologically characterized by irregularly fused glands with low-grade cellular atypia that tends to spread laterally in the mucosa. To date, the expression characteristics of the key molecules involved in CRA, including receptor tyrosine kinases (RTKs), mismatch repair (MMR) proteins, phosphatase and tensin homolog (PTEN), as well as the Epstein–Barr virus (EBV) status, have yet to be uncovered. We constructed tissue microarrays of 94 CRAs, 72 conventional-type differentiated adenocarcinomas (CDAs), and 71 intramucosal poorly cohesive adenocarcinomas (PCAs) from early gastric cancers to evaluate and compare the pathological and expression profiles of potential key molecules for molecular classification (EBV; four MMR proteins–MLH1, MSH2, PMS2, and MSH6; three RTKs–HER2, MET, and EGFR; PTEN; and p53). None of the CRAs showed MMR deficiency (0.0 % vs. 5.6 %, CRA vs. CDA, p = 0.036), HER2 overexpression (0.0 % vs. 12.5 %, p = 0.001), or loss of PTEN expression (0.0 % vs. 9.7 %, p = 0.003). Moreover, MET overexpression (4.4 % vs. 19.4 %, p = 0.004), and a mutant p53 pattern (12.4 % vs. 62.5 %, p

// Cheol Keun Park 1 , Ji Soo Park 2 , Hyo Song Kim 2 , Sun Young Rha 2 , Woo Jin Hyung 3 , Jae-Ho Cheong 3 , Sung Hoon Noh 3 , Sang Kil Lee 4 , Yong Chan Lee 4 , Yong-min Huh 5 , Hyunki Kim 1 1 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Division of Medical Oncology, Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 5 YUMS-KRIBB Medical Convergence Research Institute, Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Hyunki Kim, email: kimhyunki@yuhs.ac Keywords: gastric cancer, receptor tyrosine kinase, amplification, screening algorithm Received: June 17, 2016 Accepted: September 17, 2016 Published: September 27, 2016 ABSTRACT Although targeted therapy for receptor tyrosine kinases (RTKs) of advanced gastric cancers (AGCs) has been in the spotlight, guidelines for the identification of RTK-amplified gastric cancers (RA-GCs) have not been established. In this study, we investigate clinicopathologic characteristics of RA-GCs and propose a screening algorithm for their identification. We performed immunohistochemistry (IHC) for MLH1, MSH2, PMS2, MSH6, key RTKs (EGFR, HER2, MET), and p53, in situ hybridization for Epstein-Barr virus encoding RNA, and silver in situ hybridization (SISH) for EGFR , HER2 , and MET using tissue microarrays of 993 AGCs. On IHC, 157 (15.8%) 61, (6.15%), and 85 (8.56%) out of 993 cases scored 2+ or 3+ for EGFR, HER2, and MET, respectively. On SISH, 31.2% (49/157), 80.3% (49/61), and 30.6% (26/85) of 2+ or 3+ cases on IHC showed amplification of the corresponding genes. Of the 993 cases, 104 were classified as RA-GCs. RA-GC status correlated with older age ( P < 0.001), differentiated histology ( P = 0.001), intestinal or mixed type by Lauren classification ( P < 0.001), lymphovascular invasion ( P = 0.026), and mutant-pattern of p53 ( P < 0.001). The cases were divided into four subgroups using two classification systems, putative molecular classification and histologic-molecular classification , based on Lauren classification, IHC, and SISH results. The histologic-molecular classification showed higher sensitivity for identification of RA-GCs and predicted patient prognosis better than the putative molecular classification . In conclusion, RA-GCs show unique clinicopathologic features. The proposed algorithm based on histologic-molecular classification can be applied to select candidates for genetic examination and targeted therapy.

// Na Keum Lee 1 , Jung Hwa Lee 1 , Won Kyu Kim 2 , Seongju Yun 2 , Young Hoon Youn 1 , Chan Hyuk Park 1 , Yun Young Choi 1 , Hogeun Kim 2 , Sang Kil Lee 1 1 Yonsei Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea 2 Department of pathology, Department of Internal Medicine, Yonsei University College of Medicine, South Korea Correspondence to: Sang Kil Lee, email: sklee@yuhs.ac Keywords: PCDH10, HOTAIR, gastrointestinal stromal tumor Received: January 26, 2016 Accepted: September 12, 2016 Published: September 21, 2016 ABSTRACT HOTAIR, a long non-coding RNA (lncRNA), plays a crucial role in tumor initiation and metastasis by interacting with the PRC2 complex and the modulation of its target genes. The role of HOTAIR in gastrointestinal stromal tumors (GISTs) is remains unclear. Herein we investigate the mechanism of HOTAIR in the genesis and promotion of GISTs. The expression of HOTAIR was found to be higher in surgically resected high-risk GISTs than that in low- and intermediate-risk GISTs. Using GIST-T1 and GIST882 cells, we demonstrated that HOTAIR repressed apoptosis, was associated with cell cycle progression, and controlled the invasion and migration of GIST cells. Using a gene expression microarray and lists of HOTAIR-associated candidate genes, we suggested that protocadherin 10 (PCDH10) is a key molecule. PCDH10 expression was significantly decreased in GIST-T1 and GIST882 cells, possibly as a consequence of hypermethylation. We observed that HOTAIR induced PCDH10 methylation in a SUZ12-dependent manner. In this study, we found that the malignant character of GISTs was initiated and amplified by PCDH10 in a process regulated by HOTAIR. In summary, our findings imply that PCDH10 and HOTAIR may be useful markers of disease progression and therapeutic targets.

Background/Aims: We evaluated the characteristics of the National Cancer Screening Program (NCSP) and opinions regarding the National Endoscopy Quality Improvement Program (NEQIP). Methods: We surveyed physicians performing esophagogastroduodenoscopy and/or colonoscopy screenings as part of the NCSP via e-mail between July and August in 2015. The 32-item survey instrument included endoscopic capacity, sedation, and reprocessing of endoscopes as well as opinions regarding the NEQIP. Results: A total of 507 respondents were analyzed after the exclusion of 40 incomplete answers. Under the current capacity of the NCSP, the typical waiting time for screening endoscopy was less than 4 weeks in more than 90% of endoscopy units. Performance of endoscopy reprocessing was suboptimal, with 28% of respondents using unapproved disinfectants or not knowing the main ingredient of their disinfectants and 15% to 17% of respondents not following reprocessing protocols. Agreement with the NEQIP was optimal, because only 5.7% of respondents did not agree with NEQIP; however, familiarity with the NEQIP was suboptimal, because only 37.3% of respondents were familiar with the NEQIP criteria. Conclusions: The NEQIP remains suboptimal in Korea. Given the suboptimal performance of endoscopy reprocessing and low familiarity with the NEQIP, improved quality in endoscopy reprocessing and better understanding of the NEQIP should be emphasized in Korea. (Gut Liver 2016;10:699-705)

// Hyo Song Kim 1 , Su-Jin Shin 2 , Seung-Hoon Beom 1 , Minkyu Jung 1 , Yoon Young Choi 3 , Taeil Son 3 , Hyoung-Il Kim 3 , Jae-Ho Cheong 3 , Woo Jin Hyung 3 , Sung Hoon Noh 3 , Hyunsoo Chung 4 , Jun Chul Park 4 , Sung Kwan Shin 4 , Sang Kil Lee 4 , Yong Chan Lee 4 , Woong Sub Koom 5 , Joon Seok Lim 6 , Hyun Cheol Chung 1 , Sun Young Rha 1 , Hyunki Kim 2 1 Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea 5 Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Republic of Korea 6 Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Hyunki Kim, email: kimhyunki@yuhs.ac Sun Young Rha, email: rha7655@yuhs.ac Keywords: gastric cancer, molecular subtypes, immunohistochemistry, in-situ hybridization Received: April 04, 2016 Accepted: May 29, 2016 Published: June 16, 2016 ABSTRACT Gastric cancer (GC) is a leading cause of death. We aim to establish a clinically relevant assay that encompasses recent molecular classifications and provides useful clinical information in a large cohort of GC patients. A consecutive series of 438 GC patients that underwent palliative chemotherapy between 2014 and 2015 were assessed using 10 GC panels: EBER in-situ hybridization, immunohistochemistry for mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (RTKs; HER2, EGFR, and MET), PTEN, and p53 protein. With a median of one aberration, 3.3 % of samples analyzed were Epstein-Barr virus (EBV)-positive; 4.8%, MMR-deficient. RTKs were overexpressed in 218 patients; EGFR was most commonly overexpressed (39.9%), followed by HER2 (13.5%) and MET (12.1%). Furthermore, 2.5 % and 10.7 % of cases had simultaneous overexpression of three and two RTKs, respectively. p53 overexpression/null tumors were identified in 259 patients (59.1%), and PTEN loss was identified in 89 patients (20.3%). EBV-positivity was mutually exclusive with MMR-deficiency, predominantly identified in male patients, and these tumors were undifferentiated with proximal location. p53 mutant type was significantly found predominantly in the EBV-negative (60.6% vs 14.3%, P=0.001) and HER2-positive (78.0% vs 56.2%, P=0.002) groups. We described a molecular spectrum of distinct GC subtypes using clinically applicable assay. This assay will provide a convenient screening tool and facilitate the development of targeted agents in clinical trials.