Endoscopic Features of Synchronous Multiple Early Gastric Cancers: Findings from a Nationwide Cohort.

INTRODUCTION: We investigated the factors associated with synchronous multiple early gastric cancers and determined their localization. METHODS: We analyzed 8,191 patients who underwent endoscopic submucosal dissection for early gastric cancers at 33 hospitals in Japan from November 2013 to October 2016. Background factors were compared between single-lesion (n = 7,221) and synchronous multi-lesion cases (n = 970) using univariate and multivariate analyses. We extracted cases with two synchronous lesions (n = 832) and evaluated their localization. RESULTS: Significant independent risk factors for synchronous multiple early gastric cancer were older age (≥75 years old) (odds ratio [OR] = 1.257), male sex (OR = 1.385), severe mucosal atrophy (OR = 1.400), tumor localization in the middle (OR = 1.362) or lower region (OR = 1.404), and submucosal invasion (OR = 1.528 [SM1], 1.488 [SM2]). Depressed macroscopic type (OR = 0.679) and pure undifferentiated histology OR = 0.334) were more common in single early gastric cancers. When one lesion was in the upper region, the other was more frequently located in the lesser curvature of the middle region. When one lesion was in the middle region, the other was more frequently located in the middle region or the lesser curvature of the lower region. When one lesion was in the lower region, the other was more frequently located in the lesser curvature of the middle region or the lower region. CONCLUSION: Factors associated with synchronous multiple early gastric cancer included older age, male sex, severe mucosal atrophy, tumor localization in the middle or lower region, and tumor submucosal invasion. Our findings provide useful information regarding specific areas that should be examined carefully when one lesion is detected.

Autophagy-Related Gene ATG7 Polymorphism Could Potentially Serve as a Biomarker of the Progression of Atrophic Gastritis.

Cytotoxin-associated gene A (CagA) is an oncoprotein that H. pylori injects into the host's gastric epithelial cells and that induces proinflammatory cytokines, such as interleukin (IL)-18 and IL-1ß. As a result, it leads to atrophic gastritis (AG), a precancerous lesion of gastric cancer. On the other hand, host cells degrade CagA using autophagy systems. However, few studies exist about the single nucleotide polymorphisms (SNPs) in MAP1LC3A, MAP1LC3B, ATG4A, ATG4B, ATG4C, ATG7, and ATG13, which belong to the autophagy-related genes concerning AG. This study aimed to detect biomarkers associated with AG. Herein, H. pylori-positive subjects (n = 200) were divided into the AG (n = 94) and non-AG (n = 106) groups. Thirty tag SNPs were selected from the above seven candidate genes. The SNP frequency between the two groups was analyzed. The frequency of the C/T or T/T genotype at rs4683787 of ATG7 was significantly lower in the AG group than in the non-AG group (p = 0.034, odds ratio = 0.535). Based on multivariate analysis, the C/C genotype of rs4684787 and age were independently associated with gastric mucosal atrophy. This finding helps stratify the patients needing timely endoscopic screening or early eradication of H. pylori.

ATG16L1 and ATG12 Gene Polymorphisms Are Involved in the Progression of Atrophic Gastritis.

Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On the other hand, gastric epithelial cells degrade CagA using an autophagy system, which is strictly regulated by the autophagy-related (ATG) genes. This study aimed to identify SNPs in ATG5, ATG10, ATG12, and ATG16L1 associated with gastric mucosal atrophy (GMA). Here, two-hundred H. pylori-positive participants without gastric cancer were included. The degree of GMA was evaluated via the pepsinogen method. Twenty-five SNPs located in the four candidate genes were selected as tag SNPs. The frequency of each SNP between the GMA and the non-GMA group was evaluated. The rs6431655, rs6431659, and rs4663136 in ATG16L1 and rs26537 in ATG12 were independently associated with GMA. Of these four SNPs, the G/G genotype of rs6431659 in ATG16L1 has the highest odd ratio (Odds ratio = 3.835, 95% confidence intervals = 1.337-1.005, p = 0.008). Further functional analyses and prospective analyses with a larger sample size are required.

Polymorphism in autophagy-related genes LRP1 and CAPZA1 may promote gastric mucosal atrophy.

BACKGROUND: Helicobacter pylori secretes cytotoxin-associated gene A (CagA) into the gastric epithelium, causing gastric mucosal atrophy (GMA) and gastric cancer. In contrast, host cells degrade CagA via autophagy. However, the association between polymorphisms in autophagy-related genes and GMA must be fully elucidated. RESULTS: We evaluated the association between single nucleotide polymorphisms (SNPs) in autophagy-related genes (low-density lipoprotein receptor-related protein 1, LRP1; capping actin protein of muscle Z-line alpha subunit 1, CAPAZ1; and lysosomal-associated membrane protein 1, LAMP1) and GMA in 200 H. pylori-positive individuals. The frequency of the T/T genotype at rs1800137 in LRP1 was significantly lower in the GMA group than in the non-GMA group (p = 0.018, odds ratio [OR] = 0.188). The frequencies of the G/A or A/A genotype at rs4423118 and T/A or A/A genotype at rs58618380 of CAPAZ1 in the GMA group were significantly higher than those in the non-GMA group (p = 0.029 and p = 0.027, respectively). Multivariate analysis revealed that C/C or C/T genotype at rs1800137, T/A or A/A genotype at rs58618380, and age were independent risk factors for GMA (p = 0.038, p = 0.023, and p = 0.006, respectively). Furthermore, individuals with the rs1800137 C/C or C/T genotype of LRP1 had a 5.3-fold higher susceptibility to GMA. These genetic tests may provide future directions for precision medicine for individuals more likely to develop GMA. CONCLUSION: LRP1 and CAPZA1 polymorphisms may be associated with the development of GMA.

Management of colorectal high-grade dysplasia or cancer resected by cold snare polypectomy: a multicenter exploratory study.

BACKGROUND: The clinical course and surveillance strategy for patients who undergo cold snare polypectomy (CSP) for high-grade dysplasia (HGD) or cancer is unclear. We investigated the management of colorectal HGDs and cancers following CSP. METHODS: This Japanese nationwide multicenter exploratory study was retrospectively conducted on patients who had undergone CSP for colorectal HGDs or cancers and follow-up colonoscopy at least once from 2014 to 2020. We investigated the detection rate of CSP scars, local recurrence rate (LRR), risk factors for local recurrence, and follow-up strategy. This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000043670). RESULTS: We included 155 patients with 156 lesions. CSP scars were identified in 22 (31.4%), 41 (54.7%), and 10 (90.9%) patients with curative, borderline, and non-curative resection, respectively. Among them, residual tumors were observed in one (4.5%), six (14.6%), and three (30.0%) cases, respectively. The total LRR was 13.7% (95% confidence interval: 6.8-23.8). R1 resection cases (either horizontal or vertical margins positive for tumors) were associated with local recurrence (p = 0.031). Salvage endoscopic and surgical resections were performed on 21 and 10 patients, respectively. Among them, the proportion of endoscopically suspected residual tumors was significantly higher (p < 0.001) in the residual tumor-positive group (100%) than in the residual tumor-negative group (28.6%). CONCLUSIONS: LRR after CSP for HGDs or cancers was 13.7% based on scar-identified cases. Salvage endoscopic or surgical resection should be performed according to the curability of the lesion and endoscopic findings during colonoscopic surveillance.

Association between perioperative management of antiplatelet agents and risk of post-endoscopic submucosal dissection bleeding in early gastric cancer: analysis of a nationwide multicenter study.

BACKGROUND AND AIMS: Data are lacking regarding post-endoscopic submucosal dissection (ESD) bleeding in patients with early gastric cancer (EGC) who take antiplatelet agents (APAs), particularly in those taking thienopyridine and cilostazol. We aimed to clarify the association between the status of APA medication and post-ESD bleeding risk. METHODS: This study is a secondary analysis using data from a recently conducted nationwide multicenter study in Japan. We retrospectively reviewed patients treated with APAs or on no antithrombotic therapy recruited from 33 institutions who underwent ESD for EGC between November 2013 and October 2016. The primary outcome of this study was the relationship between the rate of post-ESD bleeding and the status of each APA medication. RESULTS: A total of 9736 patients were included in the analysis. Among 665 aspirin users, the continuation group was significantly associated with post-ESD bleeding (odds ratio [OR], 2.79; 95% confidence interval [CI], 1.77-4.37). Among 227 thienopyridine users, the aspirin or cilostazol replacement group was not significantly associated with post-ESD bleeding (OR, 1.85; 95% CI, .72-4.78). Among 158 cilostazol users, there was no significant association with post-ESD bleeding, irrespective of medication status. The rate of post-ESD bleeding was approximately 10% to 20% irrespective of the status of APA administration among dual-antiplatelet therapy users. No patients experienced thromboembolic events in this study. CONCLUSIONS: Replacement of thienopyridine with aspirin or cilostazol may be acceptable for minimizing both the risk of post-ESD bleeding and thromboembolism in patients with EGC. In patients on cilostazol monotherapy undergoing ESD, continuation of therapy may be acceptable.

'Underwater endoscopic mucosal resection with submucosal injection and marking' for superficial non-ampullary duodenal epithelial tumors to achieve R0 resection: a single-center case series.

OBJECTIVES: To describe an endoscopic technique named 'underwater endoscopic mucosal resection (UEMR) with submucosal injection and marking (UEMR-SIM)' and to evaluate the therapeutic characteristics of superficial non-ampullary duodenal epithelial tumors (SNADETs) < 20 mm vis-a-vis classical EMR (CEMR) and UEMR techniques. MATERIALS AND METHODS: This retrospective study included 103 consecutive SNADET patients (103 lesions) who underwent CEMR, UEMR, or UEMR-SIM. The UEMR-SIM procedure included (1) marking and submucosal injection, (2) filling of the duodenal lumen with 0.9% saline, (3) snaring of the lesion, and (4) electrosurgical removal. The procedural outcomes were compared between the UEMR-SIM and other-procedure groups. RESULTS: The en bloc resection rate was significantly higher in the UEMR-SIM group (100%) than in the CEMR group (76.8%) (p = 0.015) but was not statistically different between the UEMR-SIM and UEMR groups (88.0%) (p = 0.236). The R0 resection rate was significantly higher in the UEMR-SIM group (90.9%) than in the UEMR group (48.0%) (p = 0.001) but was not statistically different between the UEMR-SIM and CEMR groups (76.8%) (p = 0.209). CONCLUSIONS: Our study indicates that the proposed method, UEMR-SIM for SNADETs, is feasible to achieve a high R0 resection rate and a potentially low local recurrence rate.

Long-term Survival After Endoscopic Resection For Gastric Cancer: Real-world Evidence From a Multicenter Prospective Cohort.

BACKGROUND & AIMS: We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study. METHODS: We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C). RESULTS: Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS. CONCLUSION: ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Bleeding following Endoscopic Submucosal Dissection for Early Gastric Cancer in Surgically Altered Stomach.

INTRODUCTION: Few studies have focused on bleeding following endoscopic submucosal dissection (ESD) in surgically altered stomach. We aimed to reveal the bleeding risk in surgically altered stomach following ESD for early gastric cancer (EGC). METHODS: We enrolled patients with ESD for EGC at 33 institutions between 2013 and 2016. In study 1, we evaluated bleeding risk following ESD in surgically altered stomach, compared with whole stomach. In study 2, we evaluated factors associated with bleeding following ESD in patients with surgically altered stomach. RESULTS: Of 11,452 patients, 445 patients had surgically altered stomach with the bleeding rate following ESD of 4.9%. In study 1, the bleeding risk in surgically altered stomach was not significant (odds ratio [OR], 1.37; 95% confidence interval [CI], 0.87-2.17) in the multivariate logistic regression analysis. No significant results were obtained when the surgically altered stomach was subdivided into various types. In study 2, the multivariate logistic regression analysis revealed that independent risk factors for bleeding following ESD were ischemic heart disease (OR, 7.52; 95% CI, 2.00-28.25) and P2Y12 receptor antagonist (OR, 4.81; 95% CI, 1.21-19.14). DISCUSSION/CONCLUSION: In this nationwide study, we found that the bleeding risk of surgically altered stomach following ESD for EGC did not significantly differ from that of whole stomach. The risk factors for ESD in patients with surgically altered stomach were ischemic heart disease and P2Y12 receptor antagonist.

SNP rs2920280 in PSCA Is Associated with Susceptibility to Gastric Mucosal Atrophy and Is a Promising Biomarker in Japanese Individuals with Helicobacter pylori Infection.

Helicobacter pylori infection results in gastric cancer (GC) with gastric mucosal atrophy (GMA). Some single-nucleotide polymorphisms (SNPs) in the prostate stem cell antigen gene (PSCA) are associated with GC and duodenal ulcers. However, the relationship of other identified SNPs in PSCA with these diseases remains unclear. Herein, the association between PSCA SNPs and GMA among 195 Japanese individuals with H. pylori infection was evaluated. The definition of GMA or non-GMA was based on serum pepsinogen levels or endoscopic findings. Five tag PSCA SNPs were analyzed using PCR high-resolution melting curve analysis with nonlabelled probes. The frequencies of alleles and the genotypes of each tag SNP were compared between the GMA and non-GMA groups. Subsequently, a genetic test was performed using associated SNPs as biomarkers to detect patients developing GMA. Two tag PSCA SNPs (rs2920280 and rs2294008) were related to GMA susceptibility. Individuals with the rs2920280 G/G genotype or the rs2294008 T/T genotype in PSCA had 3.5- and 2.1-fold susceptibility to GMA, respectively. In conclusion, SNP rs2920280 is a possible biomarker for detecting individuals developing GMA. PSCA polymorphisms may be useful biomarkers for predicting GMA linked to GC risk and a screening endoscopy strategy to detect GC related to early stage H. pylori associated GMA.

Pyloric Incompetence Associated with Helicobactor pylori Infection and Correlated to the Severity of Atrophic Gastritis.

Duodenogastric reflux (DGR) causes bile reflux gastritis (BRG) and may develop into gastric cancer. DGR is classified as primary in non-operated stomachs or secondary to surgical intervention. Primary DGR and Helicobacter pylori (H. pylori) infection are reportedly related. However, the mechanism is not fully understood. This study aimed to elucidate the relationship between H. pylori infection and pyloric incompetence in a non-operated stomach. A total of 502 non-operated participants who underwent an upper intestinal endoscopy were prospectively enrolled. Endoscopic findings (EAC, endoscopic atrophy classification; nodular gastritis; xanthoma; fundic gland polyp; and incompetence of pylorus), sex, age, gastrin, pepsinogen (PG) I and PG II levels were evaluated. PG I/PG II ratio, anti-H. pylori-Ab positivity, and atrophic gastritis status were significantly different between the normal and incompetent pylori (p = 0.043, <0.001, and 0.001, respectively). Open-type atrophic gastritis was significantly higher in the incompetent pylori. Incompetence of the pylorus and EAC were moderately correlated (Cramer's V = 0.25). Multivariate analysis revealed that the presence of anti-H. pylori-Ab was the only independent factor associated with the incompetence of the pylorus, with an adjusted odds ratio of 2.70 (95% CI: 1.47−4.94, p = 0.001). In conclusion, pyloric incompetence was associated with H. pylori infection and moderately correlated to the severity of atrophic gastritis in non-operated stomachs.

The degree of mucosal atrophy is associated with post-endoscopic submucosal dissection bleeding in early gastric cancer.

BACKGROUND AND AIM: Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post-ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post-ESD bleeding and the degree of gastric mucosal atrophy based on H. pylori infection status. METHODS: We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post-ESD bleeding. RESULTS: There were 3935 H. pylori-positive patients and 4235 H. pylori-negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post-ESD bleeding in H. pylori-negative patients (odds ratio: 1.51, P = 0.007), but not in H. pylori-positive patients (odds ratio: 0.91, P = 0.600). Further, in H. pylori-negative, but not H. pylori-positive, patients, the rate of post-ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers. CONCLUSIONS: Nonsevere gastric mucosal atrophy was a risk factor for post-ESD bleeding in early gastric cancer in H. pylori-negative patients but not in H. pylori-positive patients.

Antithrombotics increase bleeding after endoscopic submucosal dissection for gastric cancer: Nationwide propensity score analysis.

OBJECTIVES: Post-operative bleeding is the most common adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Patients taking antithrombotic agents has increased. We evaluated the influence of antithrombotic agents on delayed bleeding in ESD for EGC. METHODS: This was a post hoc analysis of nationwide, multicenter, retrospective cohort study in Japan. Altogether, 11,452 patients who underwent ESD for EGC in 33 institutions between November 2013 and October 2016 were enrolled. The primary outcome was the incidence of delayed bleeding in patients with or without antithrombotic agents. The secondary outcome was the incidence of delayed bleeding in those who took each antithrombotic agent and the cessation status of its use compared with each matched pair of patients. We used propensity matching and inverse probability of treatment weighting (IPTW) analyses. RESULTS: There were 1353 matched pairs of patients. The incidence of delayed bleeding was 2.8% and 10.7% in those without and with antithrombotic agents, respectively (odds ratio [OR] 4.15, 95% confidence interval [CI] 2.88-5.99; P < 0.001). The IPTW analysis showed similar results (OR 4.21, 95% CI 3.48-5.08; P < 0.001). Antiplatelets, anticoagulants, and their combination increased such incidence. Heparin bridging therapy had high OR (8.80), and the continuation (OR 3.46) and cessation (OR 2.95) of antithrombotic agent use had similar risk. CONCLUSIONS: Antithrombotic agents increased the incidence of delayed bleeding in patients who underwent ESD for EGC. Continuing antithrombotics may be more appropriate than heparin bridging therapy.

Influence of hospital volume on bleeding after endoscopic submucosal dissection for early gastric cancer in Japan: a multicenter propensity score-matched analysis.

BACKGROUND: Information on whether there is a relationship between hospital volume and bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is limited. This study aimed to compare the bleeding rates after ESD for EGC according to the hospital volume. METHODS: Patients who underwent ESD for EGC at 33 institutions in Japan between November 2013 and October 2016 were included in this multicenter retrospective study. Hospital volume was categorized into three groups, based on the average annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). The bleeding rate after ESD for EGC was compared between the three hospital volume groups after propensity score matching. RESULTS: A total of 10,320 patients, including 2797 patients in the LMVG, 4646 patients in the HVG, and 2877 patients in the VHVG, were identified. Propensity score matching yielded 2002 patients in each hospital volume group, with an improved balance of confounding variables between the three groups. The bleeding rates in the LMVG, HVG, and VHVG were 4.3%, 3.7%, and 4.9%, respectively, and no significant difference was noted between the three groups. CONCLUSIONS: The bleeding rate after ESD for EGC did not differ between hospitals in Japan. The finding indicated that ESD for EGC is equally feasible across Japanese hospitals of different volumes regarding bleeding after ESD.

Risk Factors for Bleeding After Endoscopic Submucosal Dissection for Gastric Cancer in Elderly Patients Older Than 80 Years in Japan.

INTRODUCTION: As the aging of people in a society advances, the number of elderly patients older than 80 years in Japan with gastric cancer continues to increase. Although delayed ulcer bleeding is a major adverse event after endoscopic submucosal dissection (ESD), little is known about characteristic risk factors for bleeding in elderly patients undergoing ESD. This study aimed to evaluate risk factors for delayed bleeding after ESD for gastric cancer in elderly patients older than 80 years. METHODS: We retrospectively evaluated the incidence of delayed bleeding after ESD in 10,320 patients with early-stage gastric cancer resected by ESD between November 2013 and January 2016 at 33 Japanese institutions and investigated risk factors for delayed bleeding in elderly patients older than 80 years. RESULTS: The incidence of delayed bleeding in elderly patients older than 80 years was 5.7% (95% confidence interval [CI]: 4.6%-6.9%, 95/1,675), which was significantly higher than that in nonelderly (older than 20 years and younger than 80 years) patients (4.5%, 4.1%-5.0%, 393/8,645). Predictive factors for ESD-associated bleeding differed between nonelderly and elderly patients. On multivariate analysis of predictive factors at the time of treatment, risk factors in elderly patients were hemodialysis (odds ratio: 4.591, 95% CI: 2.056-10.248, P < 0.001) and warfarin use (odds ratio: 4.783, 95% CI: 1.689-13.540, P = 0.003). DISCUSSION: This multicenter study found that the incidence of delayed bleeding after ESD in Japanese patients older than 80 years was high, especially in patients receiving hemodialysis and taking warfarin. Management of ESD to prevent delayed bleeding requires particular care in patients older than 80 years.

Esophageal metastasis of renal cell carcinoma resected by endoscopic submucosal dissection: a case report.

BACKGROUND: Esophageal metastasis of renal cell carcinoma (RCC) is extremely rare. We have described herein a case of a 59-year-old man with esophageal metastasis of RCC that was endoscopically resected. CASE PRESENTATION: The case was a 59-year-old man who had undergone left nephrectomy for renal clear cell carcinoma 17 years ago and splenectomy for splenic metastasis 3 years ago. Esophagogastroduodenoscopy (EGD) performed 9 years ago revealed a small reddish elevated lesion with a smooth surface in the middle esophagus; this lesion increased in size 4 years ago. However, no biopsy was performed. The lesion continued to grow in size and was found to have become nodular during the present observation. Biopsy revealed clear cell carcinoma. Endoscopic ultrasound (EUS) revealed that the lesion had not invaded the submucosa, and contrast-enhanced computed tomography did not reveal any other metastasis. The lesion was successfully removed en bloc via endoscopic submucosal dissection (ESD). Pathologically, the tumor was detected in the subepithelium with focal infiltration of the muscularis mucosa. It consisted of monotonous cells with small nuclei and a clear cytoplasm. Immunohistological findings indicated that the tumor was a metastasis of RCC. The lateral and vertical margins were noted to be free. CONCLUSIONS: We have presented herein a case of esophageal metastasis of RCC that had progressed over 9 years and was then resected en bloc through endoscopic submucosal dissection.

Timing of bleeding and thromboembolism associated with endoscopic submucosal dissection for gastric cancer in Japan.

BACKGROUND AND AIM: This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). METHODS: We retrospectively reviewed  10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated. RESULTS: Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1). CONCLUSION: We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.

Predictive factor of recurrence after endoscopic papillectomy for ampullary neoplasms.

BACKGROUND/PURPOSE: Recurrence of ampullary neoplasms after endoscopic papillectomy (EP) has not been well elucidated. This study aimed to clarify the predictive factors for recurrences after EP. We also aimed to investigate the retreatment of the recurrent lesions and their outcomes. METHODS: This multicenter, retrospective cohort study included 96 patients with ampullary neoplasms who underwent EP at four tertiary centers between January 2000 and October 2018. RESULTS: The pathological diagnoses of resected specimens confirmed adenoma in 62 and adenocarcinoma in 34 patients (six Tis, 24 T1a, three T1b, one inconclusive). Complete resection was confirmed for 79 patients (82.3%). Recurrent lesions were observed in 13 patients (13.5%) during a median follow-up of 3 months (1-36 months) after EP. The predictive factors of recurrence were piecemeal resection, and non-negative horizontal or vertical margin in univariate analysis. Non-negative vertical margin was the only independent predictive factor of recurrence in the multivariate analysis. The recurrent lesions were treated endoscopically in 11 patients. Recurrence after the endoscopic retreatments was observed in one patient. CONCLUSIONS: Complete resection with negative vertical margin is an important factor in preventing the recurrence of ampullary neoplasms after EP. Endoscopic retreatments are also feasible for recurrent lesions.

Rebleeding in patients with delayed bleeding after endoscopic submucosal dissection for early gastric cancer.

OBJECTIVES: Delayed bleeding is a major adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Some patients may experience rebleeding after successful hemostasis for delayed bleeding, yet the details of rebleeding remain unclear. We aimed to clarify the frequency and risk factors of rebleeding. METHODS: Among 11,452 patients who underwent ESD for EGC at 33 institutions in Japan between 2013 and 2016, we analyzed 489 patients showing delayed bleeding. The rate of rebleeding was investigated. Subsequently, 15 candidate variables were evaluated for their influence on the risk of rebleeding via logistic regression analysis. RESULTS: Rebleeding occurred in 11.2% (55/489) of the enrolled patients. Multivariate analysis revealed that warfarin [odds ratio (OR), 2.71; 95% confidence interval (CI), 1.26-5.84] and a resection size >40 mm (OR, 1.99; 95% CI, 1.08-3.67) were independent risk factors for rebleeding. In the analysis of the management of warfarin after index bleeding, only warfarin discontinuation (OR, 3.66; 95% CI, 1.37-9.78) was significantly associated with rebleeding in comparison with no use of warfarin. However, many rebleeding events (75.0%) occurred following the resumption of warfarin. The rebleeding rate during discontinuation status and that in taking warfarin (continuation or resumption) were 6.1% and 20.0%, respectively. CONCLUSIONS: Rebleeding was not a rare event in patients experiencing delayed bleeding after ESD for EGC. In addition to having a resection size >40 mm, warfarin usage placed patients at high risk for rebleeding, especially at the timing of its resumption following discontinuation as well as its continuation.