Potential for expanding indications and curability criteria of endoscopic resection for early gastric cancer in elderly patients: results from a Japanese multicenter prospective cohort study.

BACKGROUND AND AIMS: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes and explored new indications and curability criteria. METHODS: We analyzed data from a Japanese multicenter, prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines) into elderly-high (>10% estimated metastatic risk) and elderly-low (EL-L) (≤10% estimated metastatic risk). RESULTS: In total, 3371 patients with 3821 EGCs were included; endoscopic submucosal dissection was the prominent treatment choice. Among them, 3586 lesions met the guidelines' ER indications, and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm and 96.0%, 64.0%, and 18.0%, respectively, for those >3 cm. Curative ER and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates after curative ER and elderly-high were 0.3% (95% confidence interval [CI], 0.2-0.6) and 3.5% (95% CI, 2.0-5.7), respectively. After EL-L, the rate was 0.9% (95% CI, 0.2-3.5) even without subsequent treatment. CONCLUSIONS: The usefulness of endoscopic submucosal dissection for elderly EGC patients was confirmed by their clinical outcomes. Lesions of ≤3 cm and EL-L emerged as new ER indication and curability criteria, respectively. (Clinical trial registration number: UMIN000005871.).

Risk factors for intraoperative and delayed perforation related with gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Perforation is one of the most important complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Several studies have examined risk factors for intraoperative and delayed perforations, but most were retrospective analyses with small numbers of patients. METHODS: This study represents a secondary analysis of a Japanese multicenter prospective cohort study. We investigated the factors associated with each type of perforation using 9015 patients with 9975 EGCs undergoing ESD between July 2010 and June 2012. RESULTS: Intraoperative perforation occurred in 198 patients (2.2%) with 203 lesions (2.0%), necessitating emergency surgery for four lesions (0.04% [2.0%, 4/203]). Delayed perforation occurred in another 37 patients (0.4%) with 42 lesions (0.4%), requiring emergency surgery for 12 lesions (0.12% [28.6%, 12/42]). Factors showing significant independent correlations with intraoperative perforation were upper or middle third of the stomach; remnant stomach or gastric tube; procedure time ≥100 min; tumor size >35 mm; body mass index (BMI) < 18.5 kg/m2; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m2; ≥75 years; ulceration; and tumor size >20 mm. Intraoperative perforation occurred most frequently at the greater curvature in the upper third of the stomach (7.9%), whereas delayed perforation occurred most frequently at the greater curvature in the middle third (1.2%). CONCLUSION: This multicenter prospective cohort study clarified the risk and risk factors of intraoperative and delayed perforation related to ESD for EGCs, providing information to help endoscopists reduce perforation.

Association between continuous cessation or reduction of drinking alcohol and improvement of multiple dysplastic lesions in patients with esophageal squamous cell carcinoma after endoscopic resection.

BACKGROUND: Multiple development of squamous cell carcinoma (SCC) in the upper aerodigestive tract has been explained by the 'field cancerization phenomenon' associated with alcohol drinking. Squamous dysplastic lesion is clinically visualised as a Lugol-voiding lesion (LVL) by chromoendoscopy. Whether cessation or reduction of alcohol drinking improves multiple LVL and reduces the risk of field cancerization has not been elucidated. METHODS: We analysed 330 patients with newly diagnosed superficial esophageal SCC (ESCC) enrolled in the cohort study. The grade of LVL was assessed in all patients every 6 months. We instructed the patients to stop smoking and drinking and recorded their drinking and smoking status every 6 months. RESULTS: Among 330 patients, we excluded 98 with no LVL or no drinking habit. Of the remaining 232 patients, 158 continuously ceased or reduced their drinking habit. Patients who ceased or reduced their drinking habit significantly showed improvement in the grade of LVL. Multivariate analysis showed that continuous cessation or reduction of drinking habit improved the grade of LVL (hazard ratio [HR] = 8.5, 95% confidence interval [CI] 1.7-153.8, p = 0.0053). Higher grade of LVL carried a high risk of multiple ESCC and head and neck SCC (HNSCC) (HR = 3.7, 95% CI 2.2-6.4, p < 0.0001). Improvement in LVL significantly decreased the risk of multiple ESCC and HNSCC (HR = 0.2, 95% CI 0.04-0.7, p = 0.009). CONCLUSIONS: This is the first report indicating that field cancerization was reversible and cessation or reduction of drinking alcohol could prevent multiple squamous dysplastic lesion and multiple ESCC and HNSCC development. CLINICAL TRIALS REGISTRY NUMBER: UMIN000001676.

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).

Diagnostic performance of endoscopy for subsquamous extension of superficial adenocarcinoma of the esophagogastric junction.

OBJECTIVES: Extension of adenocarcinoma of the esophagogastric junction under the squamous epithelium may lead to errors when determining lateral margins. However, the characteristics of subsquamous extension are unclear. Herein, we evaluated the prevalence and characteristics of subsquamous extension of adenocarcinoma of the esophagogastric junction and the diagnostic performance of endoscopy for this condition. METHODS: Eighty-nine consecutive patients with superficial adenocarcinoma of the esophagogastric junction who underwent endoscopic or surgical resection at a tertiary cancer center between January 2010 and December 2017 were retrospectively evaluated. Endoscopic subsquamous extension was defined as a submucosal tumor-like elevation covered by squamous epithelium and/or a brownish area with abnormal microvessels on the squamous epithelium observed using narrow-band imaging. The diagnostic performance of endoscopy for subsquamous extension was evaluated using histological subsquamous extension as gold standard. RESULTS: Thirty-nine patients (44%) had histological subsquamous extension. Proton pump inhibitor use was significantly associated with histological subsquamous extension [odds ratio: 4.65; 95% confidence interval (CI): 1.77-12.2]. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of endoscopic subsquamous extension were 56% (95% CI: 40-72%), 96% (86-99%), 92% (73-99%), 74% (62-84%) and 79% (69-87%), respectively. The median length difference between histological and endoscopic subsquamous extension was 2 mm (range: -6 to 9 mm). CONCLUSIONS: The sensitivity of endoscopic diagnosis of subsquamous extension was unsatisfactory. The endoscopic length of subsquamous extension tended to be underestimated. An oral safety margin of one centimeter is reasonable during endoscopic resection of adenocarcinoma of the esophagogastric junction.IMPACT STATEMENT This study will contribute significantly to the literature because this is the first study to determine the difference between the lengths of subsquamous extension detected endoscopically and histologically. This study determines the prevalence of subsquamous extension and identifies characteristics associated with subsquamous extension. An understanding of the risk of subsquamous extension is important when choosing a treatment strategy and planning the resection margins in patients with adenocarcinoma of the esophagogastric junction. This study provides patients with subsquamous extension characteristics and suggests a method for accurately diagnosing this condition.

Superficial non-ampullary duodenal epithelial tumors now: endoscopic diagnosis and therapy.

With the recent increase in the frequency of duodenal tumor detection, significant progress has been made in endoscopic diagnosis and treatment. Although the first guidelines were issued in Japan, patient treatment varies widely among institutions. There is a need for improving the quality of endoscopic diagnosis and more curative and safer treatments. Biopsy is the standard diagnostic method; however, the diagnostic accuracy of endoscopic biopsy is not so high. Therefore, the differentiation of superficial non-ampullary duodenal epithelial tumors from non-neoplastic lesions is being developed. The incidence of lymph node and distant metastases of duodenal epithelial tumors is extremely rare in intramucosal carcinomas, and they are considered good candidates for endoscopic treatment if the technical difficulties can be resolved. Adverse events associated with endoscopic treatment are greatly reduced at advanced facilities through novel resection and closure methods, and further improvements are expected in the future. Clarifying the risk of metastatic recurrence may lead to the development of more appropriate treatments and curative resection criteria.

Comparison of treatment outcomes between endoscopic submucosal dissection with the needle-type knife and insulated-tip knife for superficial esophageal neoplasms.

Our study aimed to compare the treatment outcomes between endoscopic submucosal dissection (ESD) with an insulated-tip knife (ESD-IT) and a needle-type knife (ESD-N) for large superficial esophageal neoplasms, as no study of this kind has been previously reported. We used the dataset of a multicenter, randomized controlled trial that compared conventional ESD (C-ESD) and traction-assisted ESD (TA-ESD) for superficial esophageal neoplasms. We compared the procedural outcomes between ESD-IT and ESD-N in a post hoc analysis and conducted sub-analyses based on traction assistance and electrical knife type. We included 223 (EST-IT, n = 169; ESD-N, n = 54) patients with no significant differences in baseline characteristics. The operator handover rate due to ESD difficulties was significantly higher in ESD-N (ESD-IT = 0.6% vs. ESD-N = 13.0%, P = 0.001), while the injection volume was significantly higher in ESD-IT than in ESD-N (40.0 vs. 20.5 mL, P < 0.001). Other outcomes were comparable between both groups (procedural time: 51.0 vs. 49.5 minute, P = 0.89; complete resection: 90.5% vs. 90.7%, P > 0.99; and complication rate: 1.8% vs. 3.7%, P = 0.60 for ESD-IT and ESD-N, respectively). In the sub-analyses, the handover rate was significantly lower with TA-ESD than with C-ESD for ESD-N (3.2% vs. 26.1%, P = 0.034), and a significantly smaller injection volume was used in TA-ESD than in C-ESD for ESD-IT (31.5 vs. 47.0 mL, P < 0.01). ESD with either endoscopic device achieved favorable treatment outcomes with low complication rates. The handover rate in ESD-N and the injection volume in ESD-IT improved with the traction method.

Clinical factors associated with noncurative endoscopic submucosal dissection for the expanded indication of intestinal-type early gastric cancer: Post hoc analysis of a multi-institutional, single-arm, confirmatory trial (JCOG0607).

OBJECTIVES: The multi-institutional, single-arm, confirmatory trial JCOG0607 showed excellent efficacy of endoscopic submucosal dissection (ESD) for the expanded indication of intramucosal intestinal-type early gastric cancer (EGC), which consists of two groups: lesions >2 cm if clinical finding of ulcer (cUL)-negative, or those ≤3 cm if cUL-positive because of the expected low risk of lymph node metastasis. However, the proportion of noncurative resections (NCR) requiring additional surgery was high (32.4%). This post hoc analysis aimed to explore the clinical factors associated with NCR. METHODS: As the expanded indication includes two different groups, we explored the clinical factors associated with NCR separately in cUL-negative (>2 cm) and cUL-positive (≤3 cm) groups using the log-linear model. RESULTS: Two hundred and sixty cUL-negative and 206 cUL-positive EGCs were analyzed. The proportions of NCR were 33.8% in the cUL-negative group and 29.6% in the cUL-positive group. A multivariable analysis demonstrated that moderately differentiated predominant histology diagnosed in pretreatment biopsy (risk ratio [RR] 1.93, 95% confidence interval [CI] 1.34-2.77, P < 0.001) and lesion in the upper stomach (RR 1.75, 95% CI 1.03-2.96, P = 0.038) in the cUL-negative EGCs, and tumor size >2 cm (RR 1.78, 95% CI 1.22-2.58, P = 0.003) and female sex (RR 1.62, 95% CI 1.07-2.44, P = 0.021) in the cUL-positive EGCs were independent factors associated with NCR. CONCLUSIONS: Clinical risk factors associated with NCR were different between cUL-negative and cUL-positive EGCs. To avoid NCR, we need to take these factors into account when deciding expanded indications for ESD.

Second gastric cancer after curative endoscopic resection of differentiated-type early gastric cancer: post-hoc analysis of a single-arm confirmatory trial.

BACKGROUND AND AIMS: Endoscopic resection (ER) for early gastric cancer (EGC) can preserve the stomach; however, the remaining stomach can develop second gastric cancer. Few reports have prospectively investigated the incidence and treatment outcomes of second gastric cancer. METHODS: This post-hoc analysis used the dataset of the single-arm confirmatory trial, JCOG0607. The key inclusion criteria for JCOG0607 were solitary differentiated-type EGC and no previous gastrectomy or endoscopic treatment for EGC. Three hundred seventeen patients who underwent curative ER were included in this study. Surveillance endoscopy was performed 1 to 3 months after the initial ER and subsequently annually for at least 5 years. A lesion detected ≤1 year and >1 year after the initial ER was defined as overlooked gastric cancer (OGC) and metachronous gastric cancer (MGC), respectively. RESULTS: During a median follow-up period of 6.0 years (interquartile range, 5.1-7.0), 30 OGCs and 61 MGCs were detected in 24 and 48 patients, respectively. The cumulative incidence of OGC at 1 year and MGC at 5 years was 7.6% and 12.7%, respectively. ER and gastrectomy were performed in 85 lesions and 6 lesions, respectively. Pathologic evaluation showed 78 mucosal cancers, 12 submucosal cancers, and 1 advanced cancer. Eventually, 28 OGCs and 52 MGCs fulfilled the pathologic criteria for curative ER. CONCLUSIONS: Our study was the first to reveal the actual incidence of second gastric cancer after curative ER for differentiated-type gastric cancer. Most lesions could be treated with ER. Continuous endoscopic surveillance after curative ER is important to detect second gastric cancer.

Tip-in EMR as an alternative to endoscopic submucosal dissection for 20- to 30-mm nonpedunculated colorectal neoplasms.

BACKGROUND AND AIMS: Tip-in EMR, which includes anchoring the snare tip, has recently shown a favorable en-bloc and R0 resection rate for colorectal neoplasms. Thus, Tip-in EMR may be an alternative to endoscopic submucosal dissection (ESD). We aimed to compare clinical outcomes between Tip-in EMR and ESD for large colorectal neoplasms. METHODS: This retrospective study evaluated consecutive patients who underwent Tip-in EMR or ESD for 20- to 30-mm nonpedunculated colorectal neoplasms at a Japanese tertiary cancer center between January 2014 and December 2019. Baseline characteristics, treatment results, and long-term outcomes were analyzed using 1:1 propensity score matching. RESULTS: Seven hundred nine lesions were evaluated. The Tip-in EMR group included 1 lesion with a nonlifting sign but no lesions with fold convergence. After propensity score matching, each group included 140 lesions. The ESD group showed significantly higher en-bloc resection rates (99.3% vs 85.0%) and R0 resection rates (90.7% vs 62.9%). Procedure time was significantly shorter in the Tip-in EMR group (8 minutes vs 60 minutes). The Tip-in EMR and ESD groups did not differ significantly with respect to local recurrence rate (2.1% vs 0%). CONCLUSIONS: Tip-in EMR is comparable with ESD with respect to the local recurrence rate but has a shorter procedure time, despite the lower en-bloc and R0 resection rates for 20- to 30-mm nonpedunculated colorectal neoplasms without fold convergence or nonlifting sign. Thus, Tip-in EMR could be a feasible alternative to ESD in these lesions.

Biliary obstruction and pancreatitis after duodenal stent placement in the descending duodenum: a retrospective study.

BACKGROUND: Metallic stents placed in the descending duodenum can cause compression of the major duodenal papilla, resulting in biliary obstruction and pancreatitis. These are notable early adverse events of duodenal stent placement; however, they have been rarely examined. This study aimed to assess the incidence of and risk factors for biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum. METHODS: We retrospectively reviewed data of consecutive patients who underwent metallic stent placement in the descending duodenum for malignant gastric outlet obstruction at a tertiary referral cancer center between April 2014 and December 2019. Risk factors for biliary obstruction and/or pancreatitis were analyzed using a logistic regression model. RESULTS: Sixty-five patients were included. Biliary obstruction and/or pancreatitis occurred in 12 patients (18%): 8 with biliary obstruction, 2 with pancreatitis, and 2 with both biliary obstruction and pancreatitis. Multivariate analysis indicated that female sex (odds ratio: 9.2, 95% confidence interval: 1.4-58.6, P = 0.02), absence of biliary stents (odds ratio: 12.9, 95% confidence interval: 1.8-90.2, P = 0.01), and tumor invasion to the major duodenal papilla (odds ratio: 25.8, 95% confidence interval: 2.0-340.0, P = 0.01) were significant independent risk factors for biliary obstruction and/or pancreatitis. CONCLUSIONS: The incidence of biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum was non-negligible. Female sex, absence of biliary stents, and tumor invasion to the major duodenal papilla were the primary risk factors. Risk stratification can allow endoscopists to better identify patients at significant risk and permit detailed informed consent.

Predicting the depth of superficial adenocarcinoma of the esophagogastric junction.

BACKGROUND AND AIM: Preoperative determination of the invasion depth of superficial adenocarcinoma of the esophagogastric junction is important for appropriate endoscopic or surgical resection. There are no objective criteria regarding this; therefore, we investigated the factors associated with the invasion depth of superficial adenocarcinoma of the esophagogastric junction. METHODS: This retrospective study evaluated patients with superficial adenocarcinoma of the esophagogastric junction who had undergone endoscopic or surgical resection at a Japanese tertiary cancer center between April 2004 and December 2017. We analyzed endoscopic features of intramucosal to slight submucosal (M-SM1; < 500 µm) and deep submucosal (SM2; ≥ 500 µm) adenocarcinoma of the esophagogastric junction and extracted significant factors associated with and assessed the diagnostic performance of endoscopic features for SM2 lesion. RESULTS: A total of 106 cases were included in this study. Multivariate analysis indicated that depressed or protruded type (odds ratio [OR], 11.1), lesion size ≥ 15 mm (OR, 3.11), uneven surface (OR, 6.31), and subsquamous extension (OR, 5.41) were significantly associated with SM2 adenocarcinomas of the esophagogastric junction. When the macroscopic type was depressed or protruded, high sensitivity (97%) but fair specificity (46%) were observed for SM2 adenocarcinoma of the esophagogastric junction, whereas uneven surface and subsquamous extension showed high specificity (96% and 87%) but fair sensitivity (36% and 46%). CONCLUSIONS: Depressed or protruded type, lesion size ≥ 15 mm, uneven surface, and subsquamous extension were significantly associated with the invasion depth of superficial adenocarcinoma of the esophagogastric junction. These endoscopic features are useful in determining the treatment method preoperatively.

Pretreatment risk factors for endoscopic noncurative resection of gastric cancers with undifferentiated-type components.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is recommended for the treatment of early gastric cancers with an undifferentiated-type component, clinically diagnosed as intramucosal lesions ≤ 2 cm, without ulceration. In the JCOG1009/1010 trial, ESD could be performed with stomach preservation in 70% of such patients whose pathological findings met the curative resection criteria. However, additional gastrectomy was required for the remaining 30%. We identified the pretreatment risk factors for noncurative resection. METHODS: Post-hoc analysis indicated that 336 patients were identified in the JCOG1009/1010 trial; among them, 243 and 93 patients were categorized into the curative or noncurative resection groups, respectively, based on the pathological findings of the resected specimens. We explored the pretreatment risk factors for noncurative resection and investigated their associated pathological findings. RESULTS: Multivariable analysis revealed that a pretreatment tumor size > 1 cm was an independent risk factor for noncurative resection (odds ratio, 3.538; 95% confidence interval, 2.020-6.198, P < 0.0001). Patients with a pretreatment tumor size > 1 cm (n = 172) had a histological tumor size > 2 cm (22.1% vs 4.3%, odds ratio, 6.313; 95% confidence interval, 2.73-14.599, P < 0.0001) and submucosal invasion (17.4% vs 9.1%, odds ratio, 2.000; 95% confidence interval, 1.032-3.877, P = 0.040) more frequently as noncurative resection findings compared with those with a tumor size < 1 cm (n = 164). CONCLUSIONS: Because pretreatment tumor size > 1 cm is an independent risk factor for noncurative resection, endoscopists should be aware that noncurative resection is not uncommon in ESD and fully explain the potential necessity for additional gastrectomy to patients before the procedure.

Indications of Endoscopic Submucosal Dissection for Undifferentiated Early Gastric Cancer: Current Status and Future Perspectives for Further Expansion.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a widely accepted and minimally invasive treatment for early gastric cancer (EGC) without the risk of lymph node metastasis (LNM). However, undifferentiated-type EGC (UD-EGC) is considered to have a relatively high risk of LNM. Recently, the Japan Clinical Oncology Group conducted a nonrandomized confirmatory trial (JCOG1009/1010) to evaluate the efficacy and safety of ESD for UD-EGC. Herein, we review the results of JCOG1009/1010 and the possibility of further expanding the indications for ESD. SUMMARY: JCOG1009/1010 showed excellent technical results and 5-year overall survival in patients with UD-EGC. Based on the results, ESD for UD-EGC (cT1a) of ≤2 cm without ulceration was technically feasible and acceptable for standard treatment instead of gastrectomy with lymph node dissection. A review of the EGC of mixed histological type (mixed EGC) suggested that the mixed EGC might have worse biological behavior than the pure histological type. In cases of intramucosal EGC with pure signet-ring cell carcinoma or presenting a double-layer structure, the risk of LNM might be relatively low. Thus, there is a possibility of further expanding the indications or curative evaluations. In the case of UD-EGC after noncurative resection, the data suggest that the eCura system may be applicable to UD-EGC; however, due to the small number of cases, further study is warranted. Key Message: This review summarizes the present knowledge regarding indications for UD-EGC and the possibility of further expanding them.

Bilateral Risk Assessments of Surgery and Nonsurgery Contribute to Providing Optimal Management in Early Gastric Cancers after Noncurative Endoscopic Submucosal Dissection: A Multicenter Retrospective Study of 485 Patients.

BACKGROUND AND AIMS: Surgery is recommended in early gastric cancer (EGC) after noncurative endoscopic submucosal dissection (ESD), although observation can be an alternative. We aimed to develop a tailor-made treatment strategy for noncurative EGCs by comparing the lymph node metastasis risk (LNMR) and the surgical risk. METHODS: We retrospectively identified 485 patients with differentiated-type, noncurative EGCs removed by ESD and classified them into two groups: a surgery-preferable group and an observation-preferable group, according to the clinical courses. Subsequently, LNMR and surgery-related death risk were assessed using a published scoring system and a risk calculator for gastrectomy, respectively. Finally, we investigated the optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to efficiently allocate these cases into either of two groups, surgery-preferable or observation-preferable. RESULTS: In 485 patients (surgery in 322, observation in 163), 57 and 428 patients were classified into the surgery-preferable group and the observation-preferable group, respectively. The optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to allocate the cases to the two preferable groups was 7.85 with the highest area under the curve (0.689). When cases with >7.85 LNMR over the surgery-related death risk were allocated into the surgery-preferable group and vice versa, the discriminability was 73.2%, which was sufficiently higher than that in the clinical decision (44.5%). CONCLUSION: Personalized comparison of LNMR and surgery-related death risk is helpful to provide a favorable treatment option for each patient with EGCs after noncurative ESD.

Cold snare polypectomy for superficial non-ampullary duodenal epithelial tumor: a prospective clinical trial (pilot study).

BACKGOUND: Cold snare polypectomy (CSP) can minimize the risk of adverse events and has become a standard treatment for small colorectal polyps. CSP might also be suitable for small superficial non-ampullary duodenal epithelial tumors (SNADETs). This study aimed to evaluate the safety of CSP for SNADETs. METHODS: The major indication criteria were as follows: (1) endoscopically diagnosed SNADET, (2) ≤ 10 mm, and (3) a single primary lesion. CSP was performed using an electrosurgical snare without electrocautery. Follow-up endoscopy and scar biopsy were performed 3 months after CSP. The primary endpoint was the delayed adverse events rate. RESULTS: In total, 21 patients were enrolled. Two and 19 lesions were located in the duodenal bulb and 2nd portion, respectively; the median lesion size was 8 mm. CSP was attempted for all lesions; three lesions could not be resected without electrocautery and were removed by conventional endoscopic mucosal resection (EMR). The rate of spurting bleeding after CSP was 0%. The median procedure time was 12 min, the median resected specimen size was 12 mm, and the rate of en bloc resection was 81% (17/21). No adverse events were observed intraoperatively, with no delayed adverse events after CSP. Histopathology revealed 15 adenomas, 4 cancers (intramucosal), and 2 non-neoplastic lesions. The horizontal margins were negative/positive/undetermined in 9, 1, and 11 cases, respectively. All vertical margins were negative. Only one recurrence was detected by follow-up endoscopy 3 months after CSP. CONCLUSIONS: CSP can be performed safely for small SNADETs. CLINICAL TRIAL REGISTRATION: This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm ), and the registration number is UMIN000019157.

Efficacy of polyglycolic acid sheeting with fibrin glue for perforations related to gastrointestinal endoscopic procedures: a multicenter retrospective cohort study.

OBJECTIVES: Gastrointestinal (GI) perforations are one of the major adverse events of endoscopic procedures. Polyglycolic acid (PGA) sheets with fibrin glue have been reported to close GI perforations. However, its clinical outcome has not yet been fully investigated; thus, we conducted a multicenter retrospective observational study to assess the efficacy of PGA sheeting for GI perforation. METHODS: The medical records of patients who underwent PGA sheeting for endoscopic GI perforations between April 2013 and March 2018 in 18 Japanese institutions were retrospectively analyzed. PGA sheeting was applied when the clip closure was challenging or failed to use. Perforations were filled with one or several pieces of PGA sheets followed by fibrin glue application through an endoscopic catheter. Nasal or percutaneous drainage and endoscopic clipping were applied as appropriate. Clinical outcomes after PGA sheeting for intraoperative or delayed perforations were separately evaluated. RESULTS: There were 66 intraoperative and 24 delayed perforation cases. In intraoperative cases, successful closure was attained in 60 cases (91%). The median period from the first sheeting to diet resumption was 6 days (interquartile range [IQR], 4-8.8 days). Large perforation size (≥ 10 mm) and duodenal location showed marginal significant relationship to higher closure failure of intraoperative perforations. In delayed perforation cases, all cases had successful closure. The median period from the first sheeting to diet resumption was 10 days (IQR, 6-37.8 days). No adverse events related to PGA sheeting occurred. CONCLUSION: Endoscopic PGA sheeting could be a therapeutic option for GI perforations related to GI endoscopic procedures.

Diagnostic ability of magnification endoscope with narrow-band imaging in screening esophagogastroduodenoscopy.

OBJECTIVES: Magnifying endoscopy with narrow-band imaging (M-NBI) is useful for the optical diagnosis of gastrointestinal neoplasms. However, the utility of M-NBI in screening esophagogastroduodenoscopy (EGD) is unclear. We aimed to evaluate the diagnostic ability of the magnification endoscope (ME) in screening EGD for a population with a low prevalence of upper gastrointestinal cancers. METHODS: Overall, 4887 asymptomatic examinees without a history of laryngopharyngeal and/or upper gastrointestinal neoplasms who underwent opportunistic screening EGD between April 2011 and December 2017 were enrolled in this retrospective study. The examinees were categorized into two groups depending on whether screening EGD was performed using ME (ME group) or not (non-ME group). Using a propensity score-matched analysis, the diagnostic ability of EGD was compared between the two groups. RESULTS: In total, 1482 examinees (30%) were allocated to the ME group and 3405 (70%) to the non-ME group. Thirty-five epithelial neoplasms were detected in 30 examinees (0.6%). The groups were matched for baseline characteristics (1481 pairs). Both groups showed no significant difference in the epithelial neoplasm detection rate (0.8% vs. 0.3%; P = 0.14). The biopsy rate was significantly lower in the ME group than in the non-ME group (12% vs. 15%; P = 0.003). The positive predictive value (PPV) for biopsy was significantly higher in the ME group than in the non-ME group (6.6% vs. 2.8%; P = 0.048). CONCLUSIONS: Using an ME for screening EGD in an apparently healthy, asymptomatic population could reduce unnecessary biopsies by improving PPV for biopsy without decreasing the epithelial neoplasm detection rate.

Endoscopic submucosal dissection versus surgery in elderly patients with early gastric cancer of relative indication for endoscopic resection.

OBJECTIVES: Surgery is recommended for early gastric cancer (EGC) beyond the endoscopic resection (ER)-indication for the risk of lymph node metastasis; however, ER may be chosen as a "relative ER-indication" considering age and comorbidities. This study aimed to compare outcomes of endoscopic submucosal dissection (ESD) only and surgery (primary surgery and additional surgery after non-curative ESD) among elderly patients with relative ER-indication EGC and to further assess prognostic factors. METHODS: Outcomes of ESD and surgery (417 cases; 114 ESD, 303 surgery) in elderly patients (≥75 years) with relative ER-indication EGC were retrospectively analyzed. Prognostic factors were also examined. RESULTS: During the observation period (median; ESD, 34 months; surgery, 61 months), 29% of ESD and 35% of surgery patients died, including 4% and 5% from gastric cancer (GC), respectively. ESD showed lower overall survival (OS) than surgery (P = 0.027) but comparable disease-free survival (P = 0.916). OS-associated factors were age and prognostic nutritional index (PNI) in males (age ≥79, hazard ratio [HR] 2.21, P = 0.001; PNI <45, HR 2.06, P = 0.031) and age in females (age ≥82, HR 4.06, P = 0.004). Treatment was not a prognostic factor in either subgroup. Pathological category ≥pT1b2 (submucosal invasion ≥500 µm) and lymphovascular invasion (LVI) were significantly associated with GC death (mortality: ≥pT1b2, 7.7%, P = 0.002; LVI, 10.1%, P < 0.001). CONCLUSIONS: In elderly patients with relative ER-indication EGC, ESD may have comparable long-term efficacy to surgery, and treatment selection had a minor contribution to OS. For patients with poor preoperative prognostic factors, diagnostic ESD may be performed first, followed by additional surgery based on pathological results.

Guidelines for Colorectal Cold Polypectomy (supplement to "Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection").

The Japan Gastroenterological Endoscopy Society published the second edition of the "Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection" in 2019 to clarify the indications for colorectal endoscopic mucosal resection (EMR) and endoscopic submucosal dissection and to ensure appropriate preoperative diagnoses as well as effective and safe endoscopic treatment in front-line clinical settings. Endoscopic resection with electrocautery, including polypectomy and EMR, is indicated for colorectal polyps. Recently, the number of facilities introducing and implementing cold polypectomy without electrocautery has increased. Herein, we establish supplementary guidelines for cold polypectomy. Considering that the level of evidence for each statement is limited, these supplementary guidelines must be verified in clinical practice.