Randomized, Double-blind, Active-controlled Phase 3 Study to Evaluate Efficacy and Safety of Zastaprazan compared to Esomeprazole in Erosive Esophagitis.

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker (P-CAB) developed to treat gastroesophageal reflux disease. This study aims to evaluate the efficacy and safety of zastaprazan compared to esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, non-inferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary endpoint was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate at week 4, symptom response and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) (P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than esomeprazole group (95.14% (137/144) vs. 87.68% (121/138); P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the two groups (P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is non-inferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

Efficacy and safety of HIP1601 (dual delayed-release esomeprazole) 40 mg in erosive esophagitis compared to HGP1705 (delayed-release esomeprazole) 40 mg: a multicenter, randomized, double-blind, non-inferiority study.

BACKGROUND: Proton-pump inhibitors (PPIs) are the most effective drugs for treating acid-related disorders. However, once-daily dosing with conventional PPIs fail to fully control acid secretion over 24 h. This study aimed to compare the efficacy and safety of HIP1601 (dual delayed-release esomeprazole) and HGP1705 (delayed-release esomeprazole) in patients with erosive esophagitis (EE). METHODS: We enrolled 213 patients with EE randomized in a 1:1 ratio to receive 40 mg HIP1601 (n = 107) or HGP1705 (n = 106) once daily for 4 or 8 weeks. The primary endpoint was the EE healing rate, confirmed by endoscopy up to week 8. GERD-related symptoms and treatment-emergent adverse events were compared between both groups. RESULTS: By week 8, the estimated healing rates of EE were 97.8% and 96.8% in the HIP1601 and HGP1705 groups, respectively, with a 95% confidence interval of -4.7 to 7.2. After 4 or 8 weeks of treatment, the EE healing rate at week 4, complete resolution rate of symptoms, time to sustained resolution of symptoms, and number of rescue medications used were similar in both groups. The proportion of heartburn- and acid regurgitation-free nights by week 4 were higher in the HIP1601 group compared to the HGP1705 group, but the difference did not reach clinical significance (87.7% vs. 85.8%, P = 0.514, 87.5% vs. 85.8%, P = 0.774). The number of adverse events did not differ significantly between the two groups. CONCLUSIONS: The efficacy and safety of HIP1601 40 mg were comparable to those of HGP1705 40 mg for the treatment of EE and symptomatic improvement of GERD. TRIAL REGISTRATION: NCT04080726 ( https://classic. CLINICALTRIALS: gov/ct2/show/NCT04080726 ), registration date: 25/10/2018.

Incidence and adverse clinical events of primary sclerosing cholangitis with ulcerative colitis.

PURPOSE: The aim of this study was to conduct a nationwide population-based study to estimate the incidence of primary sclerosing cholangitis in patients with ulcerative colitis (UC-PSC) and investigate healthcare use, medication use, surgery, cancer, and death as adverse clinical events of UC-PSC. METHODS: We identified incident cases of UC with (UC-PSC) or without PSC (UC-alone) between 2008 and 2018 using health insurance claims data in Korea. Univariate (crude hazard ratio (HR)) and multivariate analyses were performed to compare the risk of adverse clinical events between groups. RESULTS: A total of 14,406 patients with UC using population-based claims data were detected in the cohort. Overall, 3.38% (487/14,406) of patients developed UC-PSC. During a mean follow-up duration of approximately 5.92 years, the incidence of PSC in patients with UC was 185 per 100,000 person-years. The UC-PSC group showed statistically more frequent healthcare use (hospitalization and emergency department visits: HRs, 5.986 and 9.302, respectively; P < .001), higher immunomodulator and biologic use (azathioprine, infliximab, and adalimumab: HRs, 2.061, 3.457, and 3.170, respectively; P < .001), and higher surgery rate (operation for intestinal obstruction, and colectomy: HRs, 9.728 and 2.940, respectively; P < .001) than did the UC-alone group. The UC-PSC group also showed significantly higher colorectal cancer and biliary tract cancer (HRs, 2.799 and 36.343, respectively; P < .001) and mortality (HR, 4.257) rates than did the UC-alone group. CONCLUSION: Patients with UC-PSC have higher risks of colorectal cancer, biliary tract cancer, and death than do patients with UC-alone. Although considered a rare disease, managing this complex and costly disease requires recognition of the impact of increased burden on healthcare services.

Longitudinal trends in direct costs and healthcare utilization ascribable to inflammatory bowel disease in the biologic era: a nationwide, population-based study.

BACKGROUND AND AIM: Biologic-era data regarding the direct cost and healthcare utilization of inflammatory bowel disease at the population level are limited, especially in Asia. Thus, we aimed to investigate the nationwide prevalence, direct cost, and healthcare utilization of inflammatory bowel disease in Korea in a recent 10-year period. METHODS: Using the Korean National Health Insurance claim data from 2008 to 2017, we investigated all prescription medications and their associated direct costs, hospitalizations, and outpatient visits. We also estimated the nationwide prevalence of inflammatory bowel disease using population census data. RESULTS: The estimated inflammatory bowel disease prevalence significantly increased from 108.8/100 000 in 2008 to 140.4/100 000 in 2017. The overall annual costs for inflammatory bowel disease and the healthcare cost per capita increased from $24.5 million (in US dollars) to $105.1 million and from $458.4 to $1456.6 million, respectively (both P < 0.001). Whereas the ratio of outpatient costs increased from 35.3% to 69.4%, that of outpatient days remained steady. The total annual medication cost and proportion rose from $13.3 million to $76.8 million and from 54.2% to 73.3%, respectively, mainly due to the increasing antitumor necrosis factor cost, from $1.5 million to $49.3 million (from 11.1% to 64.1% of the total annual drug cost and from 6.3% to 46.9% of the total annual cost). CONCLUSIONS: We observed increasing trends in the prevalence, direct costs, and healthcare utilization of inflammatory bowel disease in Korea in recent years. The attributable cost was mainly driven by rising expenditures on antitumor necrosis factor medications.

Feasibility of endoscopic resection and impact of endoscopic ultrasound-based surveillance on colorectal subepithelial tumors.

BACKGROUND: Owing to the rising number of screening endoscopies and instrumental advances in endoscopic ultrasound (EUS), colorectal subepithelial tumors (SETs) are being increasingly detected. We aimed to determine the feasibility of endoscopic resection (ER) and the impact of EUS-based surveillance on colorectal SETs. METHODS: The medical records of 984 patients with incidentally detected colorectal SETs between 2010 and 2019 were retrospectively reviewed. Overall, 577 colorectal SETs underwent ER, and 71 colorectal SETs underwent serial colonoscopy for > 12 months. RESULTS: The mean tumor size (± standard deviation) of 577 colorectal SETs for which ER was performed was 7.0 ± 5.7 (median, 55; range, 1-50) mm; 475 tumors were located in the rectum and 102, in the colon. En bloc resection was achieved in 560/577 treated lesions (97.1%), and complete resection was achieved in 516/577 (89.4%). ER-related adverse events occurred in 15/577 (2.6%) patients. SETs originating from the muscularis propria showed a higher risk of ER-related adverse events and perforation than SETs arising from the mucosal or submucosal layer (odds ratio [OR] 19.786, 95% confidence interval [CI] 4.556-85.919; P = 0.002 and OR 141.250, 95% CI 11.596-1720.492; P = 0.046, respectively). Seventy-one patients were followed up after EUS without any treatment for > 12 months, during which three showed progression; eight, regression; and sixty, no changes. CONCLUSIONS: ER for colorectal SETs showed excellent efficacy and safety. Additionally, colorectal SETs without high-risk features in surveillance with colonoscopy showed an excellent prognosis.

Diagnostic performance of endoscopic ultrasonography-guided fine-needle biopsy in upper gastrointestinal subepithelial tumors measuring 2-5 cm in size.

BACKGROUND: Subepithelial tumors (SETs) in the upper gastrointestinal (GI) tract are frequently discovered during upper endoscopy, and their management is determined based on size and histopathological diagnosis. We aimed to evaluate the diagnostic performance of endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) in upper GI SETs of 2-5 cm in size. METHODS: We included 63 patients who underwent EUS-FNB for upper GI SETs of 2-5 cm in size between January 2013 and February 2020. The diagnostic yield of EUS-FNB, ability of EUS-FNB in discriminating malignant from non-malignant lesions, and histopathological concordance between EUS-FNB specimens and resected specimens were evaluated. RESULTS: Successful acquisition of macroscopic tissue cores was possible in all 63 cases, and the diagnostic yield of EUS-FNB was 92.1% (58/63). The sensitivity, specificity, and accuracy of EUS-FNB in discriminating malignant from non-malignant lesions were 100% (95% confidence interval [CI] 85.3-100%), 87.8% (95% CI 79.9-87.8%), and 92.1% (95% CI 81.8-92.1%), respectively. Of the 26 SETs that were endoscopically or surgically resected after EUS-FNB, the histopathological concordance rate between the EUS-FNB specimens and resected specimens was 100% (24/24), except in two cases of inadequate results with EUS-FNB specimens. CONCLUSION: EUS-FNB provides high diagnostic yield and high capability in discriminating malignant from non-malignant lesions in upper GI SETs of 2-5 cm in size.

Association between mucin phenotype and lesion border detection using acetic acid-indigo carmine chromoendoscopy in early gastric cancers.

BACKGROUND: For successful treatment of early gastric cancers (EGCs), it is crucial to define the horizontal border of the lesion with high accuracy. Acetic acid-indigo carmine (AI) chromoendoscopy has been used to determine the horizontal border in EGCs, but this technique is less potent in certain situations. Mucin phenotype in gastric cancers refers to biological differences in precursor lesions and differences in histopathologic findings, and it might affect AI chromoendoscopy findings. We aimed to investigate the association between mucin phenotype and AI chromoendoscopy findings in EGCs. METHODS: We prospectively evaluated 126 lesions in 126 patients with endoscopically diagnosed EGCs. Conventional endoscopy and AI chromoendoscopy findings of these lesions before treatment were prospectively analyzed. The border distinction between the lesion and surrounding mucosa was classified as distinct or indistinct on conventional endoscopy and AI chromoendoscopy, respectively. Mucin phenotypes were classified as gastric, intestinal, gastrointestinal, or null type by immunohistochemistry. RESULTS: The lesion borders were distinct in 46.8% (59/126) of the lesions assessed using conventional endoscopy and in 73.0% (92/126) of those assessed with AI chromoendoscopy (p < 0.001). The border distinction rate of differentiated-type cancers on AI chromoendoscopy was significantly higher than that on conventional endoscopy (66/71 [93.0%] vs. 34/71 [47.9%], p < 0.001), but the border distinction rate of undifferentiated-type cancers on AI chromoendoscopy was not different from that on conventional endoscopy (26/55 [47.3%] vs. 25/55 [45.5%], p = 0.848). Compared with conventional endoscopy, AI chromoendoscopy identified borders in a significantly higher percentage of gastric, intestinal, and gastrointestinal mucin types; however, there was no difference in AI chromoendoscopy findings according to the mucin phenotype (p = 0.271). CONCLUSION: AI chromoendoscopy was effective in horizontal border delineation in differentiated-type EGCs, but not in undifferentiated-type EGCs. Mucin phenotype had no effect on border distinction using AI chromoendoscopy.

Seroprevalence of Helicobacter pylori in human immunodeficiency virus-infected patients in a tertiary care hospital in Busan, South Korea.

INTRODUCTION: Human immunodeficiency virus (HIV) infection management has recently become more successful. While the life expectancy of HIV-infected patients increased, the prevalence of non-acquired immunodeficiency syndrome-defining cancers, such as gastric cancer, also increased. Helicobacter pylori is associated with gastric cancer, the most common cancer and the fourth leading cause of cancer-related deaths in South Korea, which has the highest incidence of chronic gastric mucosa inflammation. Here, the seroprevalence and risk factors of H. pylori infection in Korean HIV-infected patients were evaluated. METHODS: Three hundred HIV-infected patients attending the Outpatient Department of Pusan National University Hospital were prospectively enrolled from October 2018 to February 2019. Socio-demographic information was evaluated using questionnaires, and the serological status of H. pylori infection was analyzed for anti-H. pylori IgG antibodies. RESULTS: The overall seropositivity of H. pylori was 32.7%, and 254 patients (84.7%) were male. The risk factors significantly associated with H. pylori seropositivity were: age of 40-49 years (odds ratio [OR] = 5.00; 95% confidence interval [CI] 1.30-19.17), age of 50-59 years (OR = 3.93; 95% CI 1.05-14.73), CD4 cell counts of 350-500/µL (OR = 4.23; 95% CI 1.53-11.65), CD4 cell counts ≥500/µL (OR = 2.78; 95% CI 1.15-6.72), and a weekly average alcohol consumption of at least one alcoholic beverage (OR = 1.78; 95% CI 1.05-2.99). CONCLUSIONS: The seroprevalence of H. pylori is significantly associated with alcohol consumption, high CD4 cell count, and the age group of 40-59 years.

MicroRNA Expression in Plasma of Esophageal Squamous Cell Carcinoma Patients.

BACKGROUND: Patients with esophageal squamous cell carcinoma (ESCC) have a poor prognosis and there are no effective clinical biomarkers. Recently, stable microRNAs detected in the blood have been suggested as potential biomarkers in various cancers. Therefore, we investigated whether plasma microRNAs could be feasible biomarkers for ESCC. METHODS: Peripheral blood samples were obtained from 16 healthy volunteers and 66 ESCC patients before treatment between May 2016 and April 2021. Plasma miR-18b, miR-21, miR-31, and miR-375 expression levels were measured using reverse transcription-quantitative polymerase chain reaction. RESULTS: Compared with those in healthy controls, the expression levels of plasma miR-21 were significantly higher (P = 0.022) and those of plasma miR-31 and miR-375 were significantly lower in ESCC patients (both P < 0.001). Plasma miR-18b expression levels increased in ESCC patients, but the difference was not significant (P = 0.164). The sensitivities and specificities of miR-21, miR-31, and miR-375 for differentiating ESCC patients from healthy controls were 87.5% and 61.9%, 87.5% and 98.4%, and 87.5% and 100%, respectively. There was no difference in expression levels of plasma miR-21, miR-31, and miR-375 according to clinicopathological characteristics of sex, age, tumor size and location, histologic grade, and tumor-node-metastasis stage. CONCLUSION: Our study demonstrated that plasma miR-21, miR-31, and miR-375 could be potential biomarkers for the diagnosis of ESCC. Particularly, plasma miR-31 and miR-375 showed high sensitivity and specificity for differentiating ESCC patients from healthy controls.

Usefulness of Contrast-Enhanced CT in a Patient with Acute Phlegmonous Esophagitis: A Case Report and Literature Review.

Acute phlegmonous esophagitis is a very rare, life-threatening form of esophagitis, characterized by diffuse bacterial infection and pus formation within the submucosal and muscularis layers of the esophagus. We describe a case in which contrast-enhanced chest CT was useful for evaluating the severity of phlegmonous esophagitis, which was overlooked and underestimated by endoscopy.

Narrowband imaging with near-focus magnification for discriminating the gastric tumor margin before endoscopic resection: A prospective randomized multicenter trial.

BACKGROUND AND AIM: This study investigated the usefulness of near-focus narrowband imaging (NF-NBI) for determining gastric tumor margins compared with indigo carmine chromoendoscopy (ICC) before endoscopic submucosal dissection (ESD). METHODS: This prospective randomized controlled trial was conducted at seven teaching hospitals in Korea. Patients with gastric adenoma or differentiated adenocarcinoma undergoing ESD were enrolled and randomly assigned to the NF-NBI or ICC group. A marking dot was placed on the most proximal margin of the tumor before ESD. The primary endpoint was delineation accuracy, which was defined as presence of marking dots within 1 mm of the tumor margin under microscopic observation. RESULTS: A total of 200 patients in the NF-NBI group and 195 patients in the ICC group were included. The delineation accuracy rate was 84.5% in the NF-NBI group and 81.0% in the ICC group (P = 0.44). However, the distance from the marking dot to the margin of the tumor was significantly shorter in the NF-NBI group than in the ICC group (0.8 ± 0.8 vs 1.2 ± 1.3 mm, P < 0.01). Even after adjustment of other clinicopathological factors that are associated with difficulty of tumor delineation, NF-NBI did not show significant association with accurate delineation (odds ratio of 0.86, P = 0.60). CONCLUSIONS: This prospective multicenter study showed that NF-NBI is not superior to ICC in terms of accurately delineating gastric tumors (NCT02661945).

Long-term outcomes of endoscopically resected laterally spreading tumors with a positive histological lateral margin.

BACKGROUND: With advances in diagnostic endoscopy, the incidence of superficial colorectal tumors, including laterally spreading tumors (LSTs), has increased. However, little is known about the long-term results of LSTs with positive lateral margin after endoscopic treatment. This study aimed to evaluate the long-term clinical outcomes and risk factors for local recurrence of LSTs with positive lateral margin after initial endoscopic resection. METHODS: We performed a retrospective analysis of the medical records of 324 patients who had 363 LSTs with positive lateral margin after endoscopic resection at a tertiary academic medical center. The medical records from 2011 to 2015 were analyzed. Local recurrence was confirmed through endoscopic finding and subsequent biopsy analysis. We assessed the local recurrence rate and performed multivariate analyses to identify the factors associated with local recurrence. RESULTS: Follow-up colonoscopy was performed in 176 of 363 LSTs. The local recurrence rate was 6.3% (11/176), with a median (interquartile range [IQR]) follow-up period of 19.8 (12.4-46.5) months. In multivariate analysis, local recurrence was associated with piecemeal resection (odds ratio [OR] 6.62, 95% confidence interval [CI] 1.28-34.33; p = 0.024) and inversely associated with thermal ablation (OR 0.033, 95% CI 0.00-0.45; p = 0.011). At surveillance colonoscopy, histology of the recurrent tumor was adenoma in 10 (90.9%) of 11; these were treated endoscopically. CONCLUSIONS: In this retrospective study, we found that endoscopically resected LSTs with positive lateral margin have a low recurrence rate. Piecemeal resection was associated with higher local recurrence, and thermal ablation was inversely associated with local recurrence. Endoscopic resection with positive lateral margin combined with thermal ablation leads to a low recurrence rate.

Online registry for nationwide database of Helicobacter pylori eradication in Korea: Correlation of antibiotic use density with eradication success.

BACKGROUND: The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea. MATERIALS AND METHODS: We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through "on-line database registry" from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons. RESULTS: Finally, 6738 patients were analyzed. The overall eradication rate of first-line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P < .01), whereas that of other macrolides was significantly lower in the Gyeonggi area than in other areas (P = .01). The overall use of eradication antibiotics has increased while the eradication rate steadily decreased for 5 years. However, there was no significant correlation between antibiotic use density and eradication. CONCLUSION: There was no relationship between the eradication rate and antibiotic use density in Korea.

Digital image analysis-based scoring system for endoscopic ultrasonography is useful in predicting gastrointestinal stromal tumors.

BACKGROUND: When gastric mesenchymal tumors (GMTs) measuring 2-5 cm in size are found, whether to undergo further treatment or not is controversial. Endoscopic ultrasonography (EUS) is useful for the evaluation of malignant potential of GMTs, but has limitations, such as subjective interpretation of EUS images. Therefore, we aimed to develop a scoring system based on the digital image analysis of EUS images to predict gastrointestinal stromal tumors (GISTs). METHODS: We included 103 patients with histopathologically proven GIST, leiomyoma or schwannoma on surgically resected specimen who underwent EUS examination between January 2007 and June 2018. After standardization of the EUS images, brightness values, including the mean (Tmean), indicative of echogenicity, and the standard deviation (TSD), indicative of heterogeneity, in the tumors were analyzed. RESULTS: Age, Tmean, and TSD were significantly higher in GISTs than in non-GISTs. The sensitivity and specificity were almost optimized for differentiating GISTs from non-GISTs when the critical values of age, Tmean, and TSD were 57.5 years, 67.0, and 25.6, respectively. A GIST-predicting scoring system was created by assigning 3 points for Tmean ≥ 67, 2 points for age ≥ 58 years, and 1 point for TSD ≥ 26. When GMTs with 3 points or more were diagnosed as GISTs, the sensitivity, specificity, and accuracy of the scoring system were 86.5%, 75.9%, and 83.5%, respectively. CONCLUSIONS: The scoring system based on the information of digital image analysis is useful in predicting GISTs in case of GMTs that are 2-5 cm in size.

Histopathologic discrepancies between endoscopic forceps biopsy and endoscopic resection specimens in superficial esophageal squamous neoplasms.

BACKGROUND AND AIM: Endoscopic forceps biopsy results that reflect the final pathologic results of an entire lesion are essential for making accurate diagnoses and appropriate therapeutic decisions for patients with superficial esophageal squamous neoplasms (SESNs). This study investigated the histopathologic discrepancies between endoscopic forceps biopsy and endoscopic resection specimens to elucidate the factors contributing to such discrepancies. METHODS: This retrospective observational study involved 77 patients (84 lesions) who underwent endoscopic resections for SESNs, between January 2005 and August 2017, at the Pusan National University Hospital. The SESNs were classified as low-grade intraepithelial neoplasms (LGINs), high-grade intraepithelial neoplasms (HGINs), or squamous cell carcinomas (SCCs). Following slide reviews, the histopathologic concordance between endoscopic forceps biopsy and endoscopic resection specimens was assessed, in each case. RESULTS: The histopathologic discrepancy rate between the endoscopic forceps biopsy and endoscopic resection specimens was 34.5% (29/84 lesions). Among the 29 diagnostically discordant lesions, upgrades and downgrades of the histopathologic diagnoses occurred for 27 and 2 lesions, respectively. The predominant discrepancies results in lesion upgrades from HGIN to SCC (n = 21) and from LGIN to SCC (n = 5). The two downgraded cases included one from SCC to HGIN and one from HGIN to LGIN. Multivariate analyses identified two factors that were significantly associated with the histopathologic discrepancies: upper esophageal location (odds ratio, 7.743; 95% confidence interval, 1.031-58.174; P = 0.047) and tumor area per biopsy ≥ 158.6 mm2 /biopsy (odds ratio, 5.933; 95% confidence interval, 1.051-44.483; P = 0.044). CONCLUSION: Histopathologic discrepancies were observed between endoscopic forceps biopsy and endoscopic resection specimens in patients with SESNs. Tumor location and tumor area/biopsy were both significantly associated with the discrepancies.

Circulating tumor cells detected using fluid-assisted separation technique in esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is one of the aggressive gastrointestinal tract cancers. Detection of circulating tumor cells (CTCs) in peripheral blood from patients with various malignancies has been reported to have diagnostic, prognostic, and therapeutic implications. We aimed to evaluate CTCs in patients with ESCC and assess the clinical significance of CTCs in the early diagnosis of ESCC. METHODS: Peripheral blood samples for CTCs analyses were prospectively obtained from 73 patients with ESCC prior to treatment between March 2015 and June 2018. CTCs were detected using a centrifugal microfluidic system with a new fluid-assisted separation technique. Blood samples from 31 healthy volunteers were used as controls. RESULTS: After creating a receiver operating characteristic curve to determine the optimal CTC threshold to differentiate patients with ESCC from healthy controls, sensitivity and specificity were most optimized at a CTC threshold of two per 7.5 mL of blood. Among 66 subjects with ≥ 2 CTCs per 7.5 mL of blood, 63 (95.5%) had ESCC. Among 38 subjects with < 2 CTCs per 7.5 mL of blood, 28 (73.7%) were healthy controls. When using this threshold, the sensitivity and specificity for differentiating patients with ESCC from healthy controls were 86.3% and 90.3%, respectively. CTC count was associated with tumor-node-metastasis stage, especially lymph node metastasis, but there was no correlation with any other relevant clinicopathologic variable. CONCLUSIONS: Our results suggest that CTCs detected using fluid-assisted separation technique could be helpful for early diagnosis of ESCC. Further large-scale prospective studies are warranted to validate our findings.

Morphologic pattern analysis of submucosal deformities identified by endoscopic ultrasonography for predicting the depth of invasion in early gastric cancer.

BACKGROUND: The aims of this study are to evaluate the usefulness of submucosal deformity pattern analysis with endoscopic ultrasonography (EUS) for predicting the depth of invasion in early gastric cancer (EGC) and the treatment results of endoscopic submucosal dissection (ESD). METHODS: The endoscopic and EUS parameters of 345 patients with endoscopically suspected EGC who underwent endoscopic or surgical resection between July 2012 and May 2017 were retrospectively reviewed. All patients were classified into three categories as follows according to the morphologic type of submucosal deformity identified by EUS: (1) no submucosal deformity, (2) wedge-shaped deformity, and (3) arch-shaped deformity. The presence of an arch-shaped submucosal deformity on EUS and an active endoscopic ulcer or surrounding mucosal fold convergence/clubbing on conventional endoscopy were defined as suggestive of deep submucosal cancer invasion (SCI). RESULTS: Upper location (p = 0.034) and the presence of an arch-shaped submucosal deformity on EUS (p < 0.001) were significant predictors of deep submucosal invasion, with the presence of an arch-shaped submucosal deformity showing the highest predictive value (odds ratio of 26.27). The overall diagnostic accuracy of EUS for predicting deep SCI was 83.5%, with a sensitivity of 84.0% and a specificity of 83.3%, which were significantly higher than those of conventional endoscopy. A larger lesion size and the presence of an arch-shaped submucosal deformity were significant factors associated with noncurative resection after ESD. CONCLUSIONS: Submucosal deformity pattern analysis with EUS can provide more accurate information than conventional endoscopy for predicting deep SCI. The presence of an arch-shaped submucosal deformity on EUS was an effective predictor of deep SCI and noncurative resection.

Tumor localization using radio-frequency identification clip marker: experimental results of an ex vivo porcine model.

PURPOSE: With the widespread use of minimally invasive surgery, tumor detection is becoming more difficult. We present the experimental results of a radio-frequency identification (RFID) lesion detection system in an ex vivo porcine model. METHODS: The efficacy and feasibility of a newly developed RFID lesion detection system were examined. It was applied to the stomach and colon of pigs weighing 40 kg. The RFID clip was attached to the upper and lower mucosal sides of the stomach. Colon specimens with thin and thick walls were used. The clipped sites were marked on the serosa by a pin. The longest distance from the pin the RFID tag could be detected was measured 25 times in each direction. RESULTS: In the upper gastric wall, the RFID tag detection distance was 4.5 ± 0.9 mm, 5.6 ± 0.7 mm, 12.5 ± 0.7 mm, and 5.3 ± 0.5 mm in the four directions, respectively (right, left, upper, and lower). In the antrum, the RFID tag detection distance was 5.8 ± 0.7 mm, 6.9 ± 0.5 mm, 5.6 ± 0.5 mm, and 3.7 ± 0.5 mm in the four directions. In the thin colon, the RFID tag detection distance was 6.3 ± 0.5 mm, 5.0 ± 0.5 mm, 9.7 ± 0.7 mm, and 6.4 ± 0.4 mm in the four directions. In the thick colon, the RFID tag detection distance was 3.5 ± 0.8 mm, 6.6 ± 0.5 mm, 8.4 ± 0.6 mm, and 9.8 ± 0.5 mm in the four directions. The area of detection was smallest for the antrum (83.7 mm2) and similar for the other sites (150.6, 154.7 and 157.7 mm2 for the upper body, thin colon, and thick colon, respectively). CONCLUSIONS: The distance at which the RFID tag was detected was usually within 10 mm. These results indicate the feasibility of the clinical application of the add-on clip and RFID tag as a marker for identifying the location of various gastrointestinal tumors.