Progression of duodenal neoplasia to advanced adenoma in patients with familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) have a lifetime risk of developing duodenal adenomas approaching 100%, and the relative risk for duodenal cancer compared with the general population is high. We conducted a retrospective study to investigate the progression of non-ampullary duodenal adenomas (NADAs) and risk factors for advanced lesions in patients with FAP. METHODS: Of 248 patients with 139 pedigrees at 2 institutes, we assessed 151 patients with 100 pedigrees with a pathogenic germline variant in the adenomatous polyposis coli gene, excluding mosaic variants. We evaluated the prevalence of NADAs in patients with FAP, the progression of these adenomas to advanced adenoma during the observation period, and the risk factors for the lifetime development of high-grade dysplasia (HGD), large (≥ 10 mm) duodenal adenomas, and Spiegelman stage IV. RESULTS: During the median observation period of 7 years, the incidences of patients with NADAs, with more than 20 polyps, with polyps ≥ 10 mm, with HGD, and with stage IV at the last esophagogastroduodenoscopy were increased 1.6-fold, 1.7-fold, 5-fold, 22-fold, and 9-fold, respectively. Intramucosal cancer occurred in three patients (2%), but no patients developed invasive cancer during the observation period because we performed endoscopic intervention for advanced adenomas. Stage progression was observed in 71% of 113 patients. Stage IV was more common in women, patients with a history of colectomy, and those with a 3' side mutation in their adenomatous polyposis coli gene. CONCLUSIONS: NADAs in patients with FAP frequently become exacerbated. Our findings suggest that patients with FAP who develop duodenal adenomas should be surveyed to prevent the development of duodenal cancer.

Short-term outcomes of endoscopic resection for colorectal neuroendocrine tumors: Japanese multicenter prospective C-NET STUDY.

OBJECTIVES: The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. METHODS: Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. RESULTS: A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. CONCLUSION: ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.

Evaluation of a new method, "non-injection resection using bipolar soft coagulation mode (NIRBS)", for colonic adenomatous lesions.

BACKGROUND/AIMS: Endoscopic resection of all colorectal adenomatous lesions with a low complication rate, simplicity, and negative residuals is challenging. Hence, we developed a new method called "non-injection resection using bipolar soft coagulation mode (NIRBS)" method, adapted for colorectal lesions. In addition, we evaluated the effectiveness of this method. METHODS: We performed NIRBS throughout a 12-month period for all colorectal lesions which snare resection was acceptable without cancerous lesions infiltrating deeper than the submucosal layer. RESULTS: A total of 746 resected lesions were included in the study, with a 4.5 mm mean size (range, 1-35 mm). The major pathological breakdowns were as follows: 64.3% (480/746) were adenomas, and 5.0% (37/746) were intraepithelial adenocarcinomas (Tis lesions). No residuals were observed in any of the 37 Tis lesions (mean size, 15.3 mm). Adverse events included bleeding (0.4%) but no perforation. CONCLUSIONS: NIRBS allowed the resection of multiple lesions with simplicity because of the non-injection and without perforating due to the minimal burn effect of the bipolar snare set in the soft coagulation mode. Therefore, NIRBS can be used to resect adenomatous lesions easily, including Tis lesions, from small to large lesions without leaving residuals.

Feasibility of underwater endoscopic mucosal resection for endoscopic management of gastric neoplasms in patients with familial adenomatous polyposis.

BACKGROUND: Underwater endoscopic mucosal resection (UEMR) has been developed as an effective endoscopic intervention for colon, rectum, and duodenum neoplasms. However, there are no comprehensive reports regarding the stomach, and its safety and efficacy are unknown. We aimed to examine the feasibility of UEMR for gastric neoplasms in patients with familial adenomatous polyposis (FAP). METHODS: We retrospectively extracted data of patients with FAP who underwent endoscopic resection (ER) for gastric neoplasms at Osaka International Cancer Institute from February 2009 to December 2018. Elevated gastric neoplasms of ≤ 20 mm in diameter were extracted, and conventional endoscopic mucosal resection (CEMR) and UEMR were compared. Furthermore, outcomes after ER until March 2020 were examined. RESULTS: 91 endoscopically resected gastric neoplasms were extracted from 31 patients with 26 pedigrees, and 12 neoplasms underwent CEMR and 25 neoplasms underwent UEMR was compared. The procedure time was shorter for UEMR than for CEMR. There was no significant difference between en bloc resection and R0 resection rates by EMR methods. CEMR and UEMR showed postoperative hemorrhage rates of 8% and 0%, respectively. Residual/local recurrent neoplasms were identified in four lesions (4%), but additional endoscopic intervention (three UEMR and one cauterization) resulted in a local cure. CONCLUSION: UEMR was feasible in gastric neoplasms of FAP patients, especially in elevated lesions and those of ≤ 20 mm in diameter.

Efficacy and safety of intensive downstaging polypectomy (IDP) for multiple duodenal adenomas in patients with familial adenomatous polyposis: a prospective cohort study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) risk developing multiple duodenal adenomas (MDAs), leading to duodenal cancer and death. We investigated the efficacy and safety of intensive downstaging polypectomy (IDP) for MDAs integrated with new-generation procedures. METHODS: This prospective phase II study, conducted at a tertiary cancer center, enrolled patients with FAP who had MDAs. We performed IDP including cold snare/forceps polypectomy (CSP/CFP) and underwater endoscopic mucosal resection (UEMR). The primary end point was the downstaging of Spigelman stage at 1-year follow-up. RESULTS: 2424 duodenal polyps in 58 patients with FAP underwent IDP, including 2413 CSPs in 57 patients, seven CFPs in one patient, and four UEMRs in four patients. Only one major adverse event was observed (grade 3 hyperamylasemia) without clinical manifestations. We performed additional UEMR, CSP, and CFP for one, 12, and 22 patients, respectively, during initial follow-up. Overall, 55 patients completed protocol examination; the Spigelman stage was significantly reduced at the 1-year follow-up endoscopy (P < 0.001), with downstaging observed in 39 patients (71 %). Among the 26 patients with Spigelman stage IV at initial examination and protocol completion, 23 (88 %) showed downstaging. There was no major change in Spigelman stages from 1-year follow-up esophagogastroduodenoscopy to a median of 37 months (range 3-56). CONCLUSIONS: IDP, including new-generation procedures, showed significant downstaging with acceptable adverse events for MDA in patients with FAP, even those with advanced-stage disease. Lesion selection for different resection techniques may be important for suitable and sustainable management of MDA in patients with FAP.

Gastric neoplasms in patients with familial adenomatous polyposis: endoscopic and clinicopathologic features.

BACKGROUND AND AIMS: Gastric neoplasms in patients with familial adenomatous polyposis (FAP) occur at a high rate and can cause death. The endoscopic findings of gastric neoplasms in these patients are characteristic but not well recognized. To identify the relevant characteristics to enable early detection, we retrospectively investigated endoscopic findings of gastric neoplasms in patients with FAP and then compared the clinical, histopathologic, and genetic features among subgroups. METHODS: Of 234 patients with 171 pedigrees at 2 institutes, 56 cases (24%, 133 gastric neoplasms) with 44 pedigrees were examined. Immunostaining was performed for histopathologic evaluation by 1 blinded pathologist. According to the endoscopic findings, gastric neoplasms were divided into 4 types based on location (L: antrum and pylorus, UM: the rest of the stomach) and color (W: white, T: translucent, R: reddish) and their clinicopathologic features examined. RESULTS: Of the cases, 93% could be classified into a single type. Among histologic phenotypes, high-grade dysplasia was present in 26% (type L), 41% (type UM-W), 0% (type UM-T), and 22% (type UM-R). The immunologic phenotype comprised the gastric type in 69% (93% in Type UM) and the intestinal phenotype, including the mixed type, in 31% (61% in type L). Moreover, 96% of patients had concurrent duodenal neoplasms. Adenomatous polyposis coli gene status was identified in 93% of patients; the pathogenic variant was detected in 98% but did not influence any endoscopic features. CONCLUSIONS: Gastric neoplasms in patients with FAP were stratified into 4 types according to their endoscopic findings. The endoscopic phenotype was related to the histopathologic phenotype but not to germline variants.

Delineating the extent of esophageal squamous cell carcinoma.

BACKGROUND: Lugol chromoendoscopy has been conventionally used for the detection and delineation of esophageal squamous cell carcinoma (SCC). However, the boundaries of some lesions are unclear even with Lugol chromoendoscopy, and there is a risk of residual lesions or over-excision. This study aimed to evaluate the utility of narrow-band imaging (NBI) for the delineation of esophageal SCC in endoscopic resection. METHODS: Among 367 esophageal SCCs endoscopically resected between January and December 2019 at our institute, this retrospective study included consecutive lesions, which were first marked with NBI, followed by Lugol chromoendoscopy. The proportion of residual cancer, which was defined as histologically proven cancer confirmed adjacent to the scar within 1 year after endoscopic resection, was evaluated. To evaluate whether the marks added by Lugol chromoendoscopy after NBI marking were more reliable, we evaluated the presence of cancer in the iodine-unstained area outside the NBI-determined marks, i.e., the cancerous area missed by NBI. The presence of cancer in the iodine-stained areas inside the NBI-determined marks, i.e., the cancerous area missed by Lugol, was also evaluated. These were compared to assess the risk of residual cancer in endoscopic resection with NBI and Lugol chromoendoscopy. RESULTS: Among 304 lesions, 2 (0.7%) residual cancers were detected. The cancerous area missed by NBI and the cancerous area missed by Lugol were identified in 18 (6%) and 43 (14%) lesions, respectively (P = 0.001). CONCLUSIONS: NBI might be acceptable for delineating the extent of esophageal SCCs that are difficult to delineate with Lugol chromoendoscopy.

Propensity score-matched analysis of endoscopic resection for recurrent colorectal neoplasms: A pilot study.

BACKGROUND AND AIM: Local residual/recurrent colorectal lesions after endoscopic resection (ER) are difficult to treat with conventional ER. Underwater endoscopic mucosal resection (UEMR) and endoscopic submucosal dissection (ESD) are reportedly effective. We investigated the appropriate indications of ESD and UEMR for recurrent colorectal lesions. METHODS: This single-center, retrospective, observational study was conducted at a tertiary cancer institute. Patients who underwent UEMR or ESD for residual/recurrent colorectal lesions after ER from October 2013 to February 2019 were enrolled. Propensity score matching was performed between the UEMR and ESD groups to compare the clinical characteristics, treatment, and outcomes. RESULTS: In total, 30 UEMRs and 21 ESDs were performed. Median (range) diameter of the lesions was 8 mm (2-22 mm) in UEMR and 15 mm (2-58 mm) in ESD. Median procedure time in UEMR was significantly shorter than that of ESD (4 min [2-15 min] vs 70 min [17-193 min], P < 0.001). En bloc and complete resection rates of ESD were significantly higher than that of UEMR (73% vs 100%, 41% vs 81%, respectively). No adverse events occurred with UEMR, but there were two cases (10%) of delayed perforation with ESD. Neither group reported recurrence after treatment. Propensity score-matched cases showed significantly shorter procedure time and hospitalization period in UEMR than in ESD. CONCLUSIONS: The outcomes of UEMR and ESD were comparable. UEMR could be a useful salvage therapy for small local residual/recurrent colorectal lesions after ER with shorter procedure time and hospitalization period.

Curative value of underwater endoscopic mucosal resection for submucosally invasive colorectal cancer.

BACKGROUND AND AIM: Occasionally, colorectal tumors without characteristics of deep submucosal invasion are found to be invasive upon pathological evaluation after endoscopic resection (ER). Because the resection depth for underwater endoscopic mucosal resection (UEMR) has not been clarified, we evaluated the feasibility of UEMR for pathologically invasive colorectal cancer (pT1-CRC). METHODS: We retrospectively investigated data on the backgrounds and outcomes of patients with pT1-CRC who underwent UEMR between January 2014 and June 2019 at our institute. As a reference standard, the backgrounds and outcomes of pT1-CRCs that had undergone conventional EMR (CEMR) were also investigated. RESULTS: Thirty-one patients (median age, 68 years [range, 32-88 years]; 22 men [71%]) were treated with UEMR. Median lesion size was 17 mm (range, 6-50 mm). The endoscopic complete resection rate was 100%. The overall en bloc resection rate was 77%, and the VM0, HM0, and R0 resection rates were 81%, 58%, and 55%, respectively. In cases of pT1a (invasion <1000 µm)-CRC (n = 14), the en bloc, VM0, and R0 resection rates were 92%, 100%, and 71%, respectively. Seventeen patients (five with risk factors for lymph node metastasis and 12 without) were followed up, and no local recurrence and distant metastasis were observed during the follow-up period (median follow-up period, 18 months [range, 6-62 months]) after UEMR. The outcomes of UEMR seemed to be comparable with those of CEMR (n = 32). CONCLUSIONS: The VM0 rate of UEMR for pT1-CRC, especially for pT1a-CRC, without characteristics of deep submucosal invasion seems feasible.

Esophageal metal stent for malignant obstruction after prior radiotherapy.

The association between severe adverse events (SAEs) and prior radiotherapy or stent type remains controversial. Patients with esophageal or esophagogastric junctional cancer who underwent stent placement (2005-2019) were enrolled in this retrospective study conducted at a tertiary cancer institute in Japan. The exclusion criteria were follow-up period of < 1 month and insufficient data on stent type or cancer characteristics. We used Mann-Whitney's U test for quantitative data and Fisher's exact test for categorical data. Multivariate analysis was performed using a logistic regression model. 107 stents were placed. Low radial-force stents (L group) were used in 51 procedures and high radial-force stents (H group) in 56 procedures. SAEs developed after nine procedures, the median interval from stent placement being 6 days (range, 1-141 days). SAEs occurred more frequently in the H (14%: 8/56) than in the L group (2%: 1/51) (P = 0.03). In patients who had undergone prior radiotherapy, SAEs were more frequent in the H (36%: 4/11) than in the L group (0%: 0/13) (P = 0.03). Re-obstruction and migration occurred after 16 and three procedures, respectively; these rates did not differ significantly between groups (P = 0.59, P = 1, respectively). Low radial-force stents may reduce the risk of SAEs after esophageal stenting.

Long-term outcomes after endoscopic submucosal dissection for differentiated-type early gastric cancer that fulfilled expanded indication criteria: A prospective cohort study.

BACKGROUND AND AIM: Endoscopic resection for early gastric cancer (EGC) is widely performed. However, there is still a paucity of strong evidence regarding long-term outcomes after endoscopic submucosal dissection (ESD) for the expanded indication criteria of the Japanese guidelines (ver. 2010). METHODS: Endoscopic submucosal dissection was performed in patients with EGC that met the expanded indication criteria: (i) cT1a, differentiated-type EGC of 2 to 5 cm, ulcer negative or (ii) cT1a, differentiated-type EGC of ≤3 cm, ulcer positive. Patients whose pathological examination fulfilled the curative resection criteria were then enrolled in this cohort study: negative vertical margin, negative lymphovascular invasion, and (i) pT1a, differentiated-type, and ulcer negative; (ii) pT1a, differentiated-type, ≤3 cm, and ulcer positive; or (iii) pT1b1 (<500-µm submucosal invasion), differentiated-type, and ≤3 cm. Patients with only a positive horizontal margin as a noncurative factor were included for follow-up. RESULTS: From September 2003 to February 2012, a total of 356 patients underwent ESD, and 214 were enrolled in the survival analysis. One hundred twenty patients (56%) had >2 cm in diameter and ulcer-negative lesions, and 94 (44%) had ≤3 cm and ulcer-positive lesions. The vital status at 5 years after ESD was confirmed in all (100%) patients. No local or metastatic recurrence was detected; however, 26 metachronous gastric cancers developed, and 1 patient died of metachronous gastric cancer. The 5-year disease-specific and overall survival rates were 99.5% (95% confidence interval [CI], 97.2%-100%) and 93.9% (95% CI, 89.8%-96.4%), respectively. CONCLUSION: ESD for EGC that fulfills the expanded criteria is feasible and shows favorable long-term outcomes.

Features of Esophageal Adenocarcinoma in Magnifying Narrow-Band Imaging.

BACKGROUND: Several endoscopic classifications for esophageal adenocarcinoma have been proposed; however, gastric adenocarcinoma is much more common than esophageal or esophagogastric junctional (EGJ) adenocarcinoma in East Asian countries. We, therefore, investigated whether an endoscopic diagnostic algorithm for gastric adenocarcinoma could be used for esophageal or EGJ adenocarcinoma. METHODS: One hundred eighteen consecutive patients who underwent endoscopic resection or surgery for intramucosal esophageal or EGJ adenocarcinoma, at the Osaka International Cancer Institute between January 2006 and December 2017, were included in this retrospective study. Their lesions were classified as Siewert type 1 or 2, and the presence of endoscopic magnifying narrow-band imaging findings for diagnosing gastric adenocarcinoma was evaluated. RESULTS: We evaluated 125 adenocarcinomas in 118 patients (29 type 1 and 96 type 2). Demarcation lines (DLs) were seen in 7 (24%) type 1 and 53 (55%) type 2 lesions. Irregular mucosal patterns were present in 2 (7%) type 1 and 22 (23%) type 2 lesions. Irregular vascular patterns were present in 26 (90%) type 1 and 50 (52%) type 2 lesions. According to the magnifying endoscopy diagnostic algorithm for gastric adenocarcinoma, only 7 (24%) type 1 and 52 (54%) type 2 lesions were correctly diagnosed as cancers (p = 0.005). CONCLUSION: The magnifying endoscopy diagnostic algorithm for gastric cancer may not be useful for esophageal or EGJ adenocarcinomas because of the low visibility of DLs, especially in Siewert type 1 adenocarcinoma.

Magnifying endoscopy with crystal violet staining for immune checkpoint inhibitor-associated colitis.

BACKGROUND AND AIM: There exists no evidence on the relationship between endoscopic and histologic findings. Furthermore, even after multiple biopsy specimens were obtained, histologic examination usually fails to show the characteristic features of immune checkpoint inhibitor-associated colitis. In this study, we explored the endoscopic and histologic findings of immune checkpoint inhibitor-associated colitis. METHODS: Patients diagnosed with immune checkpoint inhibitor-associated colitis at our hospital between March 2018 and December 2018 were retrospectively assessed. The degree of mucosal inflammation was evaluated using endoscopic inflammation grade (inactive, mild, moderate, or severe disease) and further observed using magnifying endoscopy with crystal violet staining. Pit structures were classified into three types: regularly arranged pits with circular or elliptical shape (R type), irregularly arranged pits with inhomogeneous size and morphology (IR type), and pits with reduced density or pits that partially disappeared (AD type). RESULTS: Eleven patients (median age, 71 years; range, 44-83 years) were diagnosed with immune checkpoint inhibitor-associated colitis. All characteristic histologic findings, including crypt distortion, crypt abscesses, and apoptotic bodies, were observed at sites with moderate-to-severe endoscopic inflammation but not at sites with inactive-to-mild endoscopic inflammation. Characteristic histologic features were observed in 0%, 50%, and 100% of R-type, IR-type, and AD-type mucosa, respectively. CONCLUSIONS: We revealed the possible utility of endoscopic images for selecting suitable target sites for biopsy and showed that endoscopic findings could reduce the time lag associated with tissue diagnosis and sampling errors due to biopsy.

Artificial intelligence for the detection of esophageal and esophagogastric junctional adenocarcinoma.

BACKGROUND AND AIM: Conventional endoscopy for the early detection of esophageal and esophagogastric junctional adenocarcinoma (E/J cancer) is limited because early lesions are asymptomatic, and the associated changes in the mucosa are subtle. There are no reports on artificial intelligence (AI) diagnosis for E/J cancer from Asian countries. Therefore, we aimed to develop a computerized image analysis system using deep learning for the detection of E/J cancers. METHODS: A total of 1172 images from 166 pathologically proven superficial E/J cancer cases and 2271 images of normal mucosa in esophagogastric junctional from 219 cases were used as the training image data. A total of 232 images from 36 cancer cases and 43 non-cancerous cases were used as the validation test data. The same validation test data were diagnosed by 15 board-certified specialists (experts). RESULTS: The sensitivity, specificity, and accuracy of the AI system were 94%, 42%, and 66%, respectively, and that of the experts were 88%, 43%, and 63%, respectively. The sensitivity of the AI system was favorable, while its specificity for non-cancerous lesions was similar to that of the experts. Interobserver agreement among the experts for detecting superficial E/J was fair (Fleiss' kappa = 0.26, z = 20.4, P < 0.001). CONCLUSIONS: Our AI system achieved high sensitivity and acceptable specificity for the detection of E/J cancers and may be a good supporting tool for the screening of E/J cancers.

Narrow band imaging under less-air condition improves the visibility of superficial esophageal squamous cell carcinoma.

BACKGROUND: The current virtual chromoendoscopy equipment cannot completely detect superficial squamous cell carcinoma (SCC) in the esophagus, despite its development in the recent years. Thus, in this study, we aimed to elucidate the appropriate air volume during endoscopic observation to improve the visibility of esophageal SCC. METHODS: This retrospective study included a total of 101 flat type esophageal SCCs identified between April 2017 and January 2019 at the Department of Gastrointestinal Oncology, Osaka International Cancer Institute. Video images of narrow band imaging (NBI) under both less-air and standard-air conditions were recorded digitally. Videos were evaluated by five endoscopists. Relative visibility between less-air and standard-air conditions of the brownish area, brownish color change of the epithelium, and dilated intrapapillary capillary loop (IPCL) were graded as 5 (definitely better under less-air condition) to 1 (definitely worse under less-air condition), with 3 indicating average visibility (equivalent to standard-air observation). RESULTS: The mean (standard deviation) visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs under less-air condition were 3.94 (0.58), 3.73 (0.57), and 4.13 (0.60), respectively, which were significantly better than that under standard-air condition (p < 0.0001). Esophageal SCC evaluated as ≥ 4 in the mean visibility score of the brownish area, brownish color change of the epithelium, and dilated IPCLs accounted for 50% (51/101 lesions), 34% (34/101 lesions), and 67% (68/101 lesions), respectively. CONCLUSIONS: The present results suggested that NBI with less air might improve the visibility of flat type esophageal SCC compared with NBI with standard air. Less-air NBI observation may facilitate the detection of flat type esophageal SCC. TRIAL REGISTRATION: The present study is a non-intervention trial.

Usefulness of epinephrine-added injection solution to reduce procedure time for gastric endoscopic submucosal dissection.

Background and study aims Epinephrine-added submucosal injection solution is used to facilitate hemostasis of non-variceal upper gastrointestinal bleeding and to prevent delayed bleeding of large pedunculated colorectal lesions. However, its benefit in gastric endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is unclear. The effectiveness of epinephrine-added injection solution for outcomes of gastric ESD was examined using propensity score matching analysis. Patients and methods A total of 1,599 patients with solitary EGC (83 with non-epinephrine-added solution and 1,516 with epinephrine-added solution) between 2011 and 2018 were enrolled. Propensity scores were calculated to balance the distribution of baseline characteristics: age, sex, tumor location, specimen size, presence of ulcer scar, tumor depth, histological tumor type, and operators' experience, and 1:3 matching was performed. En bloc resection rate, mean procedure time, delayed bleeding rate, and perforation rate were compared between the non-epinephrine (n = 79) and epinephrine (n = 237) groups. Results Mean procedure time was significantly shorter in the epinephrine group than in the non-epinephrine group (60 vs. 78 min, P  < 0.001). No significant difference was found in the rate of en bloc resection (both 99 %), incidence of delayed bleeding (both 6 %), or perforation (0 vs. 0.8 %) between the two groups. In multiple linear regression analysis, use of epinephrine-added solution was independently associated with short procedure time ( P  < 0.001) after adjustment for other covariates. Conclusion The results suggest that epinephrine-added injection solution is useful for reduction of gastric ESD procedure time, warranting validation in a randomized controlled trial.

Risk of recurrence when cutting into intramucosal (pT1a) cancer from the cutting-plane side during gastric endoscopic submucosal dissection.

BACKGROUND: During endoscopic submucosal dissection (ESD), procedural difficulty and poor visibility of the cutting plane sometimes cause the operator to cut into the lesion from the cutting-plane side, making the vertical margin positive (VM1) or unclear (VMX). In the present study, we evaluated the risk of recurrence of gastric cancer with VM1 /VMX after ESD. METHODS: In total, 1723 consecutive gastric cancers treated by ESD at Osaka International Cancer Institute from July 2012 to December 2017 were included in this retrospective cohort study. Among them, 231 submucosal or more deeply invasive gastric cancers were excluded because nontechnical factors may contribute to VM1 /VMX in such lesions. To quantify the risk of cutting into cancer from the cutting-plane side during ESD, the proportion of lesions with VM1 /VMX among the pT1a gastric cancers treated by ESD was calculated. The proportion of recurrence among these cases was calculated after exclusion of lesions with positive lymphovascular invasion or a positive horizontal margin in order to eliminate the obvious risk factors for recurrence. RESULTS: Among 1492 pT1a gastric cancers treated by ESD, 28 lesions (1.9 %; 95 % confidence interval [CI] 1.3 % - 2.7 %) histologically showed VM1 /VMX. No local recurrence (0.0 %; 95 %CI 0.0 % - 12.2 %) occurred among 23 cases. The median follow-up period was 41 months (range 10 - 84 months). CONCLUSIONS: No local recurrence was detected in pT1a gastric cancers after VM1 /VMX resection by ESD. Surveillance endoscopy could be adopted for such cases without additional surgery.

Stratification of gastric cancer risk using a deep neural network.

BACKGROUND AND AIM: Stratifying gastric cancer (GC) risk and endoscopy findings in high-risk individuals may provide effective surveillance for GC. We developed a computerized image- analysis system for endoscopic images to stratify the risk of GC. METHODS: The system was trained using images taken during endoscopic examinations with non-magnified white-light imaging. Patients were classified as high-risk (patients with GC), moderate-risk (patients with current or past Helicobacter pylori infection or gastric atrophy), or low-risk (patients with no history of H. pylori infection or gastric atrophy). After selection, 20,960, 17,404, and 68,920 images were collected as training images for the high-, moderate-, and low-risk groups, respectively. RESULTS: Performance of the artificial intelligence (AI) system was evaluated by the prevalence of GC in each group using an independent validation dataset of patients who underwent endoscopic examination and H. pylori serum antibody testing. In total, 12,824 images from 454 patients were included in the analysis. The time required for diagnosing all the images was 345 seconds. The AI system diagnosed 46, 250, and 158 patients as low-, moderate-, and high risk, respectively. The prevalence of GC in the low-, moderate-, and high-risk groups was 2.2, 8.8, and 16.4%, respectively (P = 0.0017). Three experienced endoscopists also successfully stratified the risk; however, interobserver agreement was not satisfactory (kappa value of 0.27, indicating fair agreement). CONCLUSION: The current AI system detected significant differences in the prevalence of GC among the low-, moderate-, and high-risk groups, suggesting its potential for stratifying GC risk.

Application of Convolutional Neural Networks for Detection of Superficial Nonampullary Duodenal Epithelial Tumors in Esophagogastroduodenoscopic Images.

OBJECTIVES: A superficial nonampullary duodenal epithelial tumor (SNADET) is defined as a mucosal or submucosal sporadic tumor of the duodenum that does not arise from the papilla of Vater. SNADETs rarely metastasize to the lymph nodes, and most can be treated endoscopically. However, SNADETs are sometimes missed during esophagogastroduodenoscopic examination. In this study, we constructed a convolutional neural network (CNN) and evaluated its ability to detect SNADETs. METHODS: A deep CNN was pretrained and fine-tuned using a training data set of the endoscopic images of SNADETs (duodenal adenomas [N = 65] and high-grade dysplasias [HGDs] [N = 31] [total 531 images]). The CNN evaluated a separate set of images from 26 adenomas, 8 HGDs, and 681 normal tissue (total 1,080 images). The gold standard for both the training data set and test data set was a "true diagnosis" made by board-certified endoscopists and pathologists. A detected tumor was marked with a rectangular frame on the endoscopic image. If it overlapped at least a part of the "true tumor" diagnosed by board-certified endoscopists, the CNN was considered to have "detected" the SNADET. RESULTS: The trained CNN detected 94.7% (378 of 399) of SNADETs on an image basis (94% [280 of 298] of adenomas and 100% [101 of 101] of HGDs) and 100% on a tumor basis. The time needed for screening the 399 images containing SNADETs and all 1,080 images (including normal images) was 12 and 31 seconds, respectively. DISCUSSION: We used a novel algorithm to construct a CNN for detecting SNADETs in a short time.

Effect of horizontal margin status and risk of local recurrence after endoscopic submucosal dissection for superficial esophageal cancer.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) sometimes results in en bloc resection with a positive or inconclusive horizontal margin (HM1 or HMX, respectively) on histological evaluation. The specific risk for such situations is unclear. We therefore investigated the outcome of ESD with HM1 or HMX. METHODS: This single-center retrospective study was performed at Osaka International Cancer Institute. A total of 886 esophageal squamous cell carcinoma lesions in 749 patients treated from April 2005 to June 2015 were evaluated according to the following inclusion criteria: en bloc resection with no residual lesion, HM1 or HMX status, no prior treatment, and no additional treatment. We classified HM1 and HMX into type A, in which cancer was exposed on the HM, and type B, in which the HM status was unclear because of mechanical or thermal damage. We further classified type B according to the distance between the cancer and the edge of the specimen: type B1, <1 mm and type B2, ≥1 mm. RESULTS: The resection margin was judged as HM1 or HMX in 5.0% (39/767; 95% confidence interval, 3.5-6.6%) of the en bloc resected specimens. Of 39 lesions, 30 fulfilled the inclusion criteria. Local recurrence developed in 8 of 30 lesions (26.7%). The local recurrence rates for types A, B1, and B2 were 40% (6/15 lesions), 28.5% (2/7 lesions), and 0.0% (0/8 lesions), respectively. CONCLUSIONS: Although a statistical analysis was not conducted because of the limited events, the pathological HM status may be a useful predictor of local recurrence.