Long-term Outcomes of Patients With Early Gastric Cancer Who Had Lateral Resection Margin-Positive Tumors Based on Pathology Following Endoscopic Submucosal Dissection.

PURPOSE: Long-term outcomes of patients with positive lateral margins (pLMs) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study aimed to evaluate the remnant cancer and survival rates of patients with pLMs compared with those who underwent curative resection. MATERIALS AND METHODS: A retrospective analysis was performed on consecutive patients with pLMs as the only non-curative factor of expanded indication who underwent ESD for EGC with a follow-up duration of 5 years or more. The rates of remnant cancer, recurrence, and survival were analyzed and compared to those of control patients who underwent curative resection by propensity score matching. RESULTS: Among 3,515 patients treated with ESD between 2005 and 2018, 123 non-curative EGCs were retrospectively analyzed. A total of 108 patients were followed up without endoscopic or surgical resection for 8.2 years. The control group was matched in a 1:1 ratio with patients with EGC who underwent curative resection after ESD. The observation group with pLMs had a higher incidence of remnant cancer (25.9%; 28/108) compared to that in the curative resection group (0/108; P=0.000). The remaining tumors were treated with surgical or endoscopic resection, and no additional recurrences were observed. The overall survival analysis demonstrated no significant difference between the observation and curative resection groups (P=0.577). CONCLUSIONS: No difference was observed in the overall survival rate between observation and curative resection groups. Therefore, observation may be a possible option for incomplete ESD with pLMs if continuous follow-up is performed.

Risk Assessment of Metachronous Gastric Neoplasm after Endoscopic Resection for Early Gastric Cancer According to Age at Helicobacter pylori Eradication.

Background/Aims: Helicobacter pylori eradication can reduce the incidence of metachronous gastric neoplasm (MGN) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study evaluated the risk of developing MGN after ESD for EGC based on age at H. pylori eradication. Methods: Data of patients who underwent curative ESD for EGC with H. pylori infection between 2005 and 2018 were retrospectively analyzed. The patients were allocated to four groups according to age at H. pylori eradication: group 1 (<50 years), group 2 (50-59 years), group 3 (60-69 years), and group 4 (≥70 years). Results: All patients were followed up for at least 5 years after ESD. The 5-year cumulative incidence of MGN was 2.1%, 7.0%, 8.7%, and 16.7% in groups 1, 2, 3, and 4, respectively (p<0.001), and groups 3 and 4 showed a significant increase in the risk of MGN (hazard ratio [HR], 4.66; 95% confidence interval [CI], 1.09 to 19.92 and HR, 10.75; 95% CI, 2.45 to 47.12). After adjustments for moderate to severe intestinal metaplasia based on the updated Sydney system, groups 3 and 4 remained significantly associated with MGN (HR, 4.40; 95% CI, 1.03 to 18.84 and HR, 10.14; 95% CI, 2.31 to 44.57). Conclusions: The incidence of MGN after ESD for EGC increased with age at H. pylori eradication. Age at H. pylori eradication ≥60 years was an independent risk factor for MGN, even after adjusting for the presence of advanced intestinal metaplasia.

Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study.

BACKGROUND: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.

Risk of gastric cancer in relation with serum cholesterol profiles: A nationwide population-based cohort study.

Obesity is a known risk factor for gastric cancer. However, the relationship between serum lipids and gastric cancer risk has not been fully established. We investigated the relationship between serum cholesterol levels and gastric cancer risk using a nationwide population cohort. Adults who received health care screening in 2009 from the Korean National Health Insurance Service were enrolled. Gastric cancer risk in relation to quartiles of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were compared according to sex, using adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Among 9690,168 subjects enrolled, 92,403 gastric cancer cases were diagnosed. Higher HDL-C levels were associated with lower gastric cancer risk in the total population, men, and women (aHR [for the highest quartile] = 0.98 [0.96-0.99, P < .0001], aHR = 0.98 [0.96-1.004, P = .0004], and aHR = 0.91 [0.88-0.94, P < .0001], respectively). HDL-C showed consistent trends regardless of age or statin use. Higher LDL-C levels were also associated with lower gastric cancer risk in the total population (aHR = 0.92 [0.91-0.94], P < .0001) and men (aHR = 0.94 [0.91-0.96], P < .0001), but not in women (P = .4073). A subgroup analysis of LDL-C showed significant interactions with age and statin use (Pinteraction < .0001 and Pinteraction = .0497, respectively). The risk of gastric cancer was higher in subjects with elevated LDL-C levels in the younger group (age < 55, HR [for the highest quartile] = 1.02 [0.99-1.04] in the total population; HR = 1.03 [1.003-1.06] in men), the risk was lower in subjects with elevated LDL-C in the elderly (age ≥ 55, HR = 0.93 [0.91-0.95] in the total population; HR = 0.94 [0.92-0.96] in men). Elevated TC was associated with lower gastric cancer risk in the total population (aHR = 0.95 [0.94-0.97], P < .0001), but not in each sex separately (P = .3922 in men; P = .1046 in women). Overall, higher HDL-C levels may play a protective role in gastric cancer pathogenesis. The association between LDL-C/TC and gastric cancer seems to vary according to sex, age, and statin use. Especially in young males under age 55, high LDL-C and TC levels were associated with higher risk of gastric cancer.

Optimal treatment duration of bismuth-containing quadruple therapy in Helicobacter pylori infection: A retrospective study.

The use of bismuth-containing quadruple therapy (BQT) in Helicobacter pylori eradication has been increasing. Although the recommended treatment length for BQT is 14 days, longer durations may be associated with higher rates of adverse events. The aim of this study was to evaluate the optimal duration of BQT by comparing eradication rates and adverse events among 7, 10, and 14-day regimens. A total of 328 patients treated with BQT at Seoul National University Hospital from January 2010 to May 2022 were retrospectively evaluated. The eradication rates of different treatment groups were compared using intention-to-treat (ITT) and per-protocol (PP) analyses. Baseline characteristics of the enrolled patients and adverse events were also analyzed. A total of 74, 177, and 77 patients were included in the 7-, 10-, and 14-day groups, respectively. Forty-one patients were lost during the follow-up. The eradication rates were 71.6%, 84.2%, and 80.5% (P = .106) by ITT, and 84.1%, 94.9%, and 92.5% (P = .028) by PP analysis in the 7-, 10-, and 14-day groups, respectively. The 10-day regimen showed significantly higher eradication rates than the 7-day regimen in both ITT (P = .024) and PP (P = .018) analyses. However, there were no significant differences in eradication rates between the 10- and 14-day groups in either ITT (P = .667) or PP (P = .537) analysis. Adverse event incidence was comparable among the groups (P = .835). Treatment with BQT for 10 days was as effective as 14 days without increasing the adverse events.

Decision to perform additional surgery after non-curative endoscopic submucosal dissection for gastric cancer based on the risk of lymph node metastasis: a long-term follow-up study.

BACKGROUND: Radical surgery after non-curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) may be excessive, since only 5-10% of patients have lymph node metastasis (LNM). This study investigated the suitability of the eCura system for determining the need for radical surgery after non-curative ESD. METHODS: We retrospectively investigated 343 patients who underwent non-curative ESD for EGC from 2006 to 2021 at a tertiary hospital in Korea. These patients were divided into surgery (n = 191) and observation (n = 152) groups based on whether they underwent additional surgery post-ESD. Each group was further classified into low-risk (eCura score 0-1), intermediate-risk (eCura score 2-4) and high-risk (eCura score 5-7). All patients were regularly followed-up at least annually after the initial treatment. The cumulative overall and recurrence-free survival rates were calculated for each category and compared between the surgery and observation groups. RESULTS: No significant differences in overall survival were found between the surgery and observation groups in low-risk (p = 0.168) and intermediate-risk patients (p = 0.306); however, high-risk patients had better 5-year overall survival rate in the surgery group than in the follow-up group (95.2% vs. 71.4%, p < 0.001). The 5-year recurrence-free survival rate was higher in the surgery group than in the observation group for low-risk (100% vs. 84.3%; p = 0.034), intermediate-risk (96.1% vs. 88.4%; p = 0.081) and high-risk patients (100% vs. 83.3%; p = 0.023). CONCLUSIONS: Follow-up without additional surgery after non-curative ESD can be a reasonable option for low-risk and even intermediate-risk patients according to the eCura system. However, surgery is warranted for eCura high-risk patients.

A prospective randomized noninferiority trial comparing conventional smears and SurePathTM liquid-based cytology in endoscopic ultrasound-guided sampling of esophageal, gastric, and duodenal lesions.

BACKGROUND: Several liquid-based cytology (LBC) methods are currently used, but the diagnostic accuracy of each method is not well known. We aimed to compare the diagnostic performance of SurePathTM LBC and conventional smear (CS) cytology in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples of esophageal, gastric, and duodenal lesions. METHODS: As a prospective randomized noninferiority study, patients who needed EUS-FNA due to subepithelial mass in the upper gastrointestinal tract were randomly assigned 1:1 to the LBC and CS groups. Cytologic preparation was carried out using a crossover design where 1 method was used for the first needle-pass sample and another method was used for the second needle-pass sample. The primary outcome was to compare the diagnostic performance between LBC and CS using the final diagnosis as the gold standard. RESULTS: A total of 87 patients were randomized and 60 patients were analyzed. There were no differences between LBC and CS in diagnostic accuracy (91.7% vs 86.7%, P = .380), sensitivity (97.7% vs 90.7%, P = .169), specificity (76.5% vs 76.5%, P > .99), negative predictive value (92.9% vs 76.5%, P = .225), or positive predictive value (91.3% vs 90.7%, P = .921). The background of LBC was less bloody than that of CSs (5.0% vs 53.3%, P < .001) and the sample preparation time of LBC was shorter than that of CSs (29 ±â€…7 seconds vs 90 ±â€…17 seconds, P < .001). CONCLUSION: In the EUS-FNA of a subepithelial mass in the upper gastrointestinal tract, the diagnostic performance of LBC was not inferior to that of CS. The field of view was better in LBC, because the background was less bloody and necrotic. As LBC is more convenient to perform and takes shorter time, it is expected that it can replace the CS method for EUS-FNA samples.

Lower risk of depression after smoking cessation and alcohol abstinence in patients with gastric cancer who underwent gastrectomy: A population-based, nationwide cohort study.

BACKGROUND: Although depression is associated with poor treatment outcomes in patients with cancer, little is known about whether lifestyle modifications could help prevent depression. The authors aimed to identify the effect of lifestyle modifications, including smoking cessation, alcohol abstinence, and starting regular physical activity, on new-onset depression in patients with gastric cancer who underwent surgery. METHODS: By using the Korean National Health Insurance Service database, patients with gastric cancer who underwent surgery between 2010 and 2017 were identified. Self-reported lifestyle behaviors within 2 years before and after surgery were analyzed using the health examination database. Patients were classified according to changes in lifestyle behaviors, and their risk of new-onset depression was compared. RESULTS: Among 18,902 patients, 2302 (12.19%) developed depression (26.00 per 1000 person-years). Smoking cessation (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66-0.91) and alcohol abstinence (HR, 0.79; 95% CI, 0.69-0.90) were associated with reduced risk of depression development compared with persistent smoking and persistent drinking, respectively. Starting regular physical activity was not associated with risk of depression. When lifestyle behaviors after gastrectomy were scored from 0 to 3 points (1 point each for not smoking, not drinking, and being physically active), the risk of depression tended to decrease as lifestyle scores increased from 0 points (reference) to 1 point (HR, 0.69; 95% CI, 0.55-0.83), 2 points (HR, 0.60; 95% CI, 0.50-0.76), and 3 points (HR, 0.55; 95% CI, 0.45-0.68). CONCLUSIONS: Smoking cessation and alcohol abstinence are associated with reduced risk of developing depression in patients with gastric cancer who undergo surgery.

Gastric mucosal swab as an alternative to biopsy for Helicobacter pylori detection.

BACKGROUND AND AIMS: Gastric mucosal swab may be a more sensitive sampling method than a biopsy since Helicobacter pylori (H. pylori) resides within the mucus layer. We compared the diagnostic performance of the rapid urease test (RUT) and bacterial load of H. pylori between swabs and tissue biopsy. METHODS: Overall, 276 RUTs (138 swab-RUTs (S-RUT) and 138 tissue-RUTs (T-RUT)) were performed. To diagnose H. pylori infection, RUT, H. pylori PCR, and 16S ribosomal RNA gene sequencing of tissue and swab were used, and its infection was defined as at least two positives of the six test results. The diagnostic performances of RUTs and the H. pylori bacterial load using qPCR were compared between swab and biopsy. RESULTS: The positivity rates of S-RUT and T-RUT were 35.5% (49/138) and 25.4% (35/138), respectively. The sensitivity, specificity, and accuracy of S-RUT were 98.0%, 100.0%, and 99.2%, while those of T-RUT were 70.0%, 100%, and 89.1%, respectively. The sensitivity and accuracy were significantly higher for S-RUT than for T-RUT (p < 0.05). In the patients with atrophic gastritis and intestinal metaplasia, S-RUT showed significantly higher sensitivity than T-RUT. qPCR showed that the swab contained a significantly higher H. pylori bacterial load than tissue biopsy (22.92-fold and 31.61-fold in the antrum and body (p < 0.05), respectively). CONCLUSIONS: Gastric mucosal swabs showed higher RUT accuracy and H. pylori bacterial load than a tissue biopsy. This may be an alternative to a biopsy when diagnosing H. pylori infection during endoscopy is necessary. (ClinicalTrials.gov, NCT05349578).

Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity Score-Matched Nationwide Cohort Study.

BACKGROUND: This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19). METHODS: We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included. Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration. RESULTS: Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74-0.98) and PPI users (OR, 0.62; 95% CI, 0.52-0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52-1.54) or PPI users (OR, 1.22; 95% CI, 0.60-2.51). CONCLUSION: H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.

Metachronous gastric neoplasm beyond 5 years after endoscopic resection for early gastric cancer.

BACKGROUND AND AIMS: The natural course of early gastric cancer (EGC) following endoscopic submucosal dissection (ESD) remains unclear. This study aimed to clarify the long-term clinical outcomes and risk factors of metachronous gastric neoplasm (MGN) 5 years after ESD for EGC. METHODS: We performed a retrospective analysis of patients who underwent ESD for EGC from July 2005 to October 2015 in Seoul National University Hospital. Long-term clinical outcomes and risk factors of MGN after 5 years post-ESD were evaluated. RESULTS: Among the 2059 patients who underwent ESD for EGC, 1102 were followed up for > 5 years. MGN developed in 132 patients 5 years after ESD. During the median follow-up period of 85 months, the cumulative incidences of MGN and metachronous gastric cancer were 11.7, 16.9, and 27.0 and 7.6, 10.8, and 18.7% after 5, 7, and 10 years, respectively. In multivariable analysis, male sex (odds ratio 1.770; P = 0.042), severe intestinal metaplasia (odds ratio 1.255; P = 0.000), tumor-positive lateral margin (odds ratio 2.711; P = 0.008), < 5 mm lateral safety margin (odds ratio 1.568; P = 0.050), and synchronous adenoma (odds ratio 2.612; P = 0.001) were positive predictive factors, and successful eradication of Helicobacter pylori (odds ratio 0.514; P = 0.024) was a negative predictive factor for MGN after 5 years post-ESD. CONCLUSION: The cumulative MGN incidence was high even 5 years post-ESD for EGC. Meticulous long-term endoscopic follow-up is mandatory, especially in male patients with underlying intestinal metaplasia, tumor-positive lateral margins, lateral safety margins of < 5 mm, and synchronous adenomas.

A Randomized Controlled Trial of Fibrin Glue to Prevent Bleeding After Gastric Endoscopic Submucosal Dissection.

INTRODUCTION: This study evaluated the efficacy of fibrin glue for preventing postendoscopic submucosal dissection (ESD) bleeding in high-risk patients for bleeding (expected iatrogenic ulcer size ≥40 mm or receiving antithrombotic therapy). METHODS: A multicenter, open-label, randomized controlled trial was performed at 4 tertiary medical centers in South Korea between July 1, 2020, and June 22, 2022. Patients with gastric neoplasm and a high risk of post-ESD bleeding were enrolled and allocated at 1:1 to a control group (standard ESD) or a fibrin glue group (fibrin glue applied to iatrogenic ulcers after standard ESD). The primary outcome was overall bleeding events within 4 weeks. The secondary outcomes were acute bleeding (within 48 hours post-ESD) and delayed bleeding (48 hours to 4 weeks post-ESD). RESULTS: In total, 254 patients were randomized, and 247 patients were included in the modified intention-to-treat population (125 patients in the fibrin glue group and 122 patients in the control group). Overall bleeding events occurred in 12.0% (15/125) of the fibrin glue group and 13.1% (16/122) of the control group ( P = 0.791). Acute bleeding events were significantly less common in the fibrin glue group than in the control group (1/125 vs 7/122, P = 0.034). Delayed bleeding events occurred in 11.2% (14/125) in the fibrin glue group and 7.3% (9/122) in the control group ( P = 0.301). DISCUSSION: This trial failed to show a preventive effect of fibrin glue on overall post-ESD bleeding in high-risk patients. However, the secondary outcomes suggest a potential sealing effect of fibrin glue during the acute period.

Helicobacter pylori Eradication Can Reverse Rho GTPase Expression in Gastric Carcinogenesis.

Background/Aims: Altered DNA methylation is a key mechanism of epigenetic modification in gastric cancer (GC). This study aimed to evaluate the changes in epigenetic and genetic expression of multiple Rho GTPases in Helicobacter pylori-related gastric carcinogenesis by comparing H. pylori-positive GCs and negative controls. Methods: The messenger RNA expression and methylation of Rho GTPases (RhoA, Rac1, DOCK180, ELMO1, and CDC42) were evaluated in H. pylori-negative (control) human gastric tissues and H. pylori-positive GCs by using real-time reverse transcription-polymerase chain reaction and the quantitative MethyLight assay, respectively. Changes in expression and methylation levels of the genes were also compared between H. pylori-eradicated and -persistent GCs at 1-year follow-up. Results: In GCs, the methylation and expression levels of DOCK180 and ELMO1 were higher than in controls, while RhoA and Rac1 had lower levels than controls. CDC42 had the same expression pattern as DOCK180 and ELMO1 without DNA methylation. Although methylation levels of DOCK180 and ELMO1 had no difference between H. pylori-eradicated and -persistent GCs at the index endoscopic resection, those of H. pylori-persistent GCs increased and H. pylori-eradicated GCs decreased for 1 year. The expression levels of DOCK180, ELMO1, and CDC42 in H. pylori-persistent GCs were higher than those in H. pylori-eradicated GCs over 1 year, unlike those of RhoA and Rac1. The methylation levels at index and the degrees of change over time of RhoA and Rac1 had no difference between H. pylori-persistent and -eradicated GCs. Conclusions: Epigenetic alterations of DOCK180 and ELMO1 are involved in H. pylori-related gastric carcinogenesis. This epigenetic field could be improved by H. pylori eradication.

Risk assessment of metachronous gastric cancer development using OLGA and OLGIM systems after endoscopic submucosal dissection for early gastric cancer: a long-term follow-up study.

BACKGROUND: Metachronous gastric cancer (MGC) may develop in patients undergoing curative endoscopic submucosal dissection for early gastric cancer. As gastritis and intestinal metaplasia are notable precursors to gastric cancer, we assessed MGC risk using the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM) systems. METHODS: This retrospective cohort study classified the OLGA and OLGIM stages for 916 patients who had undergone endoscopic submucosal dissection for early gastric cancer between 2005 and 2015. MGC development was followed up until 2020 and risk factors were evaluated using the Cox proportional hazards regression analysis. RESULTS: During a median follow-up of 94 months, MGC developed in 120 subjects. OLGA stages II ~ IV were significantly associated with increased MGC risk (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.05-3.19; HR 2.31, 95% CI 1.22-4.38; HR 2.36, 95% CI 1.16-4.78) in multivariable analysis, even after adjusting for the well-known positive predictor of Helicobacter pylori eradication. OLGIM stages II ~ IV also showed significant association (HR 2.86, 95% CI 1.29-6.54; HR 2.94, 95% CI 1.34-6.95; HR 3.64, 95% CI 1.60-8.29). 5-year cumulative incidence increased with each stage. Helicobacter pylori-eradicated patients with OLGIM stages 0 ~ II had significantly less MGC than non-eradicated patients (4.5% vs 11.8%, p = 0.022), which was not observed with OLGIM stages III ~ IV. CONCLUSIONS: High OLGA and OLGIM stages are independent risk factors for metachronous gastric cancer, with the OLGIM staging system being a better predictor. Patients with OLGIM stages 0 ~ II are a subgroup that may benefit more from Helicobacter pylori eradication.

Patient-Derived Organoids from Locally Advanced Gastric Adenocarcinomas Can Predict Resistance to Neoadjuvant Chemotherapy.

BACKGROUND: Patients (pts) with locally advanced gastric adenocarcinoma (LAGA) often receive neoadjuvant chemotherapy. A minority of patients do not respond to chemotherapy and thus may benefit from upfront surgery. Patient-derived organoids (PDOs) are an in vitro model that may mimic the chemotherapy response of the original tumors. METHODS: PDOs were generated from endoscopic biopsies of LAGAs prior to the initiation of chemotherapy and treated with the two chemotherapy regimens: FLOT and FOLFOX. Cell proliferation was assayed after 3-6 days. Following chemotherapy, pts underwent surgical resection, and percent pathological necrosis was determined. RESULTS: Successful PDOs were obtained from 13 of 24 (54%) LAGAs. Failure to generate PDOs were due to contamination (n = 3, 13%), early senescence (n = 3, 13%), and late senescence (n = 5, 21%). By H&E staining, there were significant similarities in tumor morphology and high concordance in immunohistochemical expression of 6 markers between tumors and derived PDOs. Four of 13 pts with successful PDOs did not undergo chemotherapy and surgery. For the remaining 9 pts, percent necrosis in resected tumors was ≤ 50% in 2 pts. The corresponding PDOs from these 2 pts were clearly chemoresistant outliers. The Pearson correlation coefficient between chemosensitivity of PDOs to FOLFOX (n = 2) or FLOT (n = 7) and percent tumor necrosis in resected tumors was 0.87 (p = 0.003). CONCLUSIONS: PDOs from pts with LAGAs in many respects mimic the original tumors from which they are derived and may be used to predict resistance to neoadjuvant chemotherapy. SYNOPSIS: Patient-derived organoids (PDOs) can serve as personalized in vitro models of patient tumors. In this study, PDOs from locally advanced gastric cancers were able to reliably predict resistance to neoadjuvant chemotherapy.

Safety of pylorus-preserving gastrectomy for gastric cancer combined with antral high-risk lesions: a comparison with endoscopic submucosal dissection.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) is a surgical treatment option for cT1N0M0 gastric cancer located in the middle third of the stomach. However, data for the long-term post-PPG clinical outcomes related to metachronous gastric neoplasms (mGNs) in the residual stomach are currently lacking. Therefore, we aimed to evaluate the safety of PPG by focusing on mGNs. METHODS: In this single-center, retrospective study, we reviewed the data for 362 patients who underwent PPG with a 3-cm antral cuff and 139 who underwent endoscopic submucosal dissection (ESD) for middle-third gastric cancer between January 2013 and December 2015. The histopathologic features of the antrum in the ESD group, which could not be determined in the PPG group, were analyzed to investigate the risk factors for mGNs. The estimated and actual incidence of mGNs in the antrum were compared in the PPG group. RESULTS: The incidence of mGNs was 6.5% (9/139) in the ESD group. The presence of a synchronous adenoma (odds ratio [OR], 8.46; 95% confidence interval [CI], 1.55-46.34), carcinoma (OR, 15.71; 95% CI, 2.67-92.56) and moderate-to-severe intestinal metaplasia (OR, 9.77; 95% CI, 1.14-83.92) were associated with a higher risk of overall mGNs. However, when confined to the antrum, no significant association was observed between these factors and mGNs. In the ESD group, 2 of 9 mGNs (1.4%) were located at the 3-cm antral cuff. In the PPG group, both mGNs (0.6%) were located in the proximal remnant stomach. CONCLUSION: Pylorus-preserving gastrectomy was a safe therapeutic option with regard to the occurrence of metachronous adenomas or carcinomas in our series. Despite the low mGN incidence in the 3-cm antral cuff after PPG, the presence of synchronous neoplasms or moderate-to-severe intestinal metaplasia was a risk factor for mGNs in the ESD group; thus, further studies on longer antral cuffs with long-term follow-up are needed.

Endoscopic submucosal dissection for papillary early gastric carcinoma: Insights from a large-scale analysis of post-gastrectomy pathology specimens.

Gastric papillary adenocarcinoma is considered a differentiated adenocarcinoma in the current endoscopic submucosal dissection indication guidelines. However, the safety of endoscopic submucosal dissection remains controversial. Currently, data regarding which papillary early gastric cancer should be considered for endoscopic submucosal dissection are unavailable. Thus, the aim of this study was to investigate lymph node metastasis and the safety of endoscopic submucosal dissection in patients with papillary early gastric cancer. This observational study recruited 4264 consecutive patients with early gastric cancer who underwent curative gastrectomy between October 2000 and December 2017 at the National Cancer Center, Korea. Of these, 45 had pathologically confirmed papillary early gastric cancer, 2106 had differentiated non-papillary early gastric cancer, and 2113 had undifferentiated early gastric cancer. Logistic regression analysis was performed to identify risk factors for lymph node metastasis. Mucosal tumors were less common in papillary early gastric cancer (37.9%) than in differentiated non-papillary early gastric cancer (48.8%) and undifferentiated early gastric cancer (60.4%) (both P < .001). Lymph node metastasis was more common in papillary early gastric cancer (20.0%) than in differentiated non-papillary early gastric cancer (9.2%) and undifferentiated early gastric cancer (11.7%; both P < .001). In multivariate analysis, non-mixed-type papillary early gastric cancer showed marginally increased odds of lymph node metastasis than differentiated early gastric cancer (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.0-6.3). Rates of lymph node metastasis (1/10, 10%) and angiolymphatic invasion (2/10, 20%) for papillary early gastric cancer meeting expanded criteria were higher than those for other histology types meeting endoscopic submucosal dissection absolute or expanded criteria (P = .03 and P < .001, respectively). Endoscopic submucosal dissection should be considered carefully for papillary early gastric cancer, especially if it meets expanded endoscopic submucosal dissection indications since it is associated with high rates of submucosal invasion and lymph node metastasis.

Extragastric Metastasis of Early Gastric Cancer After Endoscopic Submucosal Dissection With Lymphovascular Invasion and Negative Resected Margins.

PURPOSE: Lymphovascular invasion is a criterion for non-curative resection in patients who have undergone endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to determine the rate of extragastric metastasis (EGM) and identify the predictors of EGM in patients with negative resection margins (R0 resection) and lymphovascular invasion in post-ESD pathology. MATERIALS AND METHODS: A total of 2,983 patients underwent ESD for EGC. Among them, 110 had a pathology of R0 resection and positive lymphovascular invasion. Patients underwent additional gastrectomy (n=63) or further follow-up without gastrectomy (n=47). RESULTS: The 110 patients were assigned to one of the 3 groups according to ESD indications based on post-ESD pathology. The first group satisfied the absolute indication for ESD (n=18), the second group satisfied the expanded indications for ESD (n=34), and the last group satisfied the beyond indication (n=58). The number of occurrences of EGM in each group was 1 (5.6%), 3 (8.8%), and 3 (5.2%), respectively. The logistic regression analysis adjusted for age, sex, tumor size, and indication for ESD, showed that larger tumor size was associated with EGM (odds ratio, 1.76; 95% confidence interval, 1.00-3.10; P=0.048). In contrast, ESD indication criteria did not affect EGM (P=0.349). CONCLUSIONS: Tumor size was the only predictive indicator for EGM in patients who underwent R0 resection and lymphovascular invasion on post-ESD pathology. Even patients with pathology corresponding to the absolute indication criteria of ESD had lymphovascular invasion, which means that they require additional gastrectomy due to the risk of EGM.