The apelin­apelin receptor signaling pathway in fibroblasts is involved in tumor growth via p53 expression of cancer cells.

Cancer­associated fibroblasts (CAFs) are pivotal in tumor progression. TP53­deficiency in cancer cells is associated with robust stromal activation. The apelin­apelin receptor (APJ) system has been implicated in suppressing fibroblast­to­myofibroblast transition in non­neoplastic organ fibrosis. The present study aimed to elucidate the oncogenic role of the apelin­APJ system in tumor fibroblasts. APJ expression and the effect of APJ suppression in fibroblasts were investigated for p53 status in cancer cells using human cell lines (TP53­wild colon cancer, HCT116, and Caco­2; TP53­mutant colon cancer, SW480, and DLD­1; and colon fibroblasts, CCD­18Co), resected human tissue samples of colorectal cancers, and immune­deficient nude mouse xenograft models. The role of exosomes collected by ultracentrifugation were also analyzed as mediators of p53 expression in cancer cells and APJ expression in fibroblasts. APJ expression in fibroblasts co­cultured with p53­suppressed colon cancer cells (HCT116sh p53 cells) was significantly lower than in control colon cancer cells (HCT116sh control cells). APJ­suppressed fibroblasts treated with an antagonist or small interfering RNA showed myofibroblast­like properties, including increased proliferation and migratory abilities, via accelerated phosphorylation of Sma­ and Mad­related protein 2/3 (Smad2/3). In addition, xenografts of HCT116 cells with APJ­suppressed fibroblasts showed accelerated tumor growth. By contrast, apelin suppressed the upregulation of phosphorylated Smad2/3 in fibroblasts. MicroRNA 5703 enriched in exosomes derived from HCT116sh p53 cells inhibited APJ expression, and inhibition of miR­5703 diminished APJ suppression in fibroblasts caused by cancer cells. APJ suppression from a specific microRNA in cancer cell­derived exosomes induced CAF­like properties in fibroblasts. Thus, the APJ system in fibroblasts in the tumor microenvironment may be a promising therapeutic target.

[A Case of Pulmonary Pleomorphic Carcinoma in a Hemodialysis Patient Treated with Pembrolizumab].

The patient was a 67-year-old male undergoing maintenance hemodialysis due to chronic renal failure caused by diabetic nephropathy. A left upper lobe resection was carried out for non-small cell lung cancer of the left upper lobe. It was histologically confirmed as pleomorphic carcinoma pT3N0M0, Stage ⅡB. He suffered a relapse with multiple metastases occurring in both lungs 3 months following surgery. The PD-L1 tumor proportion score(TPS)was 90%, indicating a high level of expression; 200mg of pembrolizumab was administered every 3 weeks on non-dialysis days. Two courses of administration achieved a partial response. A total of 17 courses were administered until discontinuation due to drug-induced lung injury.

Underwater endoscopic mucosal resection versus endoscopic submucosal dissection for 20-30 mm colorectal polyps.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) for large polyps provides a high en bloc resection rate, accurate pathological diagnosis, and low recurrence rate. However, ESD requires advanced techniques, and underwater endoscopic mucosal resection (UEMR) is an alternative. We investigated the efficacy and safety of UEMR for 20-30 mm colorectal lesions compared with ESD. METHODS: We retrospectively evaluated systematically collected data of patients who underwent UEMR or ESD for 20-30 mm sessile colorectal lesions. Outcome measures were the incidence of local recurrence, procedure time, en bloc resection rate, and incidence of adverse events. We performed propensity score matching and inverse probability weighting adjustment to control for possible confounders. RESULTS: We evaluated 125 patients undergoing UEMR and 306 patients undergoing ESD. Using propensity score matching, we analyzed 74 lesions in each group. UEMR had a shorter procedure time than ESD [6.7 min (95% confidence interval (CI), 5.3-8.1 min) vs 64.8 min (95% CI, 57.4-72.2 min), respectively]. Although the en bloc resection rate with UEMR was inferior to ESD [61% (95% CI, 49-72%) vs 99% (95% CI, 93-100%), respectively], there was no significant difference in the local recurrence rate between the procedures [0% (95% CI, 0-4.0%) in each group]. Inverse probability weighting adjustment revealed that neither ESD nor UEMR had a significant association with local recurrence. CONCLUSIONS: Underwater endoscopic mucosal resection for 20-30  mm colorectal lesions was comparable with ESD regarding long-term outcomes, with a shorter procedure time, despite the lower en bloc resection rate.

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.

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.

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.

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.

Characterization of a novel compound that promotes myogenesis via Akt and transcriptional co-activator with PDZ-binding motif (TAZ) in mouse C2C12 cells.

Transcriptional co-activator with PDZ-binding motif (TAZ) plays versatile roles in the regulation of cell proliferation and differentiation. TAZ activity changes in response to the cellular environment such as mechanic and nutritional stimuli, osmolarity, and hypoxia. To understand the physiological roles of TAZ, chemical compounds that activate TAZ in cells are useful as experimental reagents. Kaempferol, TM-25659, and ethacridine are reported as TAZ activators. However, as each TAZ activator has a distinct property in cellular functions, additional TAZ activators are awaiting. We screened for TAZ activators and previously reported IB008738 as a TAZ activator that promotes myogenesis in C2C12 cells. In this study, we have characterized IBS004735 that was obtained in the same screening. IBS004735 also promotes myogenesis in C2C12 cells, but is not similar to IBS008738 in the structure. IBS004735 activates TAZ via Akt and has no effect on TAZ phosphorylation, which is the well-described key modification to regulate TAZ activity. Thus, we introduce IBS004735 as a novel TAZ activator that regulates TAZ in a yet unidentified mechanism.

Feasibility of underwater endoscopic mucosal resection and management of residues for superficial non-ampullary duodenal epithelial neoplasms.

BACKGROUND AND AIM: Underwater endoscopic mucosal resection (UEMR) is effective for superficial non-ampullary duodenal epithelial neoplasms (SNADEN). However, the incidence of residual lesion after UEMR, especially for large lesions (≥20 mm), and their prognosis remain unclear. We aimed to assess the incidence of residual lesions and further outcomes after UEMR for SNADEN. METHODS: We carried out a retrospective study at a tertiary cancer institute. Candidates for the study were systematically retrieved from an endoscopic and pathological database from January 2013 to April 2018. RESULTS: A total of 162 SNADEN resected with UEMR were analyzed. Median (range) procedure time was 5 (1-70) min. En bloc resection rates for large lesions (≥20 mm) and small lesions (<20 mm) were 14% and 79%, respectively. Intraprocedural bleeding occurred in one (0.6%) case, but no intraprocedural perforation occurred during the study. Delayed bleeding occurred in two (1.2%) cases and delayed perforation occurred in one (0.6%) case. A total of 157 (97%) lesions were followed up by at least one endoscopic examination. Of these lesions, residual lesions were recognized in seven cases (5%). Additional UEMR was carried out in five lesions and underwater cold snare polypectomy in one lesion. One lesion was observed without additional treatment. After salvage intervention, no cases experienced further residual lesions. CONCLUSION: Although UEMR for SNADEN can be relevant when other efficacious procedures are unavailable, careful follow up for residual lesions is required especially after piecemeal resection for large lesions.

Endoscopic detection and differentiation of esophageal lesions using a deep neural network.

BACKGROUND AND AIMS: Diagnosing esophageal squamous cell carcinoma (SCC) depends on individual physician expertise and may be subject to interobserver variability. Therefore, we developed a computerized image-analysis system to detect and differentiate esophageal SCC. METHODS: A total of 9591 nonmagnified endoscopy (non-ME) and 7844 ME images of pathologically confirmed superficial esophageal SCCs and 1692 non-ME and 3435 ME images from noncancerous lesions or normal esophagus were used as training image data. Validation was performed using 255 non-ME white-light images, 268 non-ME narrow-band images/blue-laser images, and 204 ME narrow-band images/blue-laser images from 135 patients. The same validation test data were diagnosed by 15 board-certified specialists (experienced endoscopists). RESULTS: Regarding diagnosis by non-ME with narrow-band imaging/blue-laser imaging, the sensitivity, specificity, and accuracy were 100%, 63%, and 77%, respectively, for the artificial intelligence (AI) system and 92%, 69%, and 78%, respectively, for the experienced endoscopists. Regarding diagnosis by non-ME with white-light imaging, the sensitivity, specificity, and accuracy were 90%, 76%, and 81%, respectively, for the AI system and 87%, 67%, and 75%, respectively, for the experienced endoscopists. Regarding diagnosis by ME, the sensitivity, specificity, and accuracy were 98%, 56%, and 77%, respectively, for the AI system and 83%, 70%, and 76%, respectively, for the experienced endoscopists. There was no significant difference in the diagnostic performance between the AI system and the experienced endoscopists. CONCLUSIONS: Our AI system showed high sensitivity for detecting SCC by non-ME and high accuracy for differentiating SCC from noncancerous lesions by ME.

Does cold snare polypectomy completely resect the mucosal layer? A prospective single-center observational trial.

BACKGROUND AND AIM: The true incidence of incomplete muscularis mucosa resection with cold snare polypectomy (CSP) is unknown. We examined the incidence of incomplete muscularis mucosa resection both with and without cold snare defect protrusion (CSDP). METHODS: We prospectively enrolled patients undergoing polypectomy for 4 to 9mm nonpedunculated polyps. We evaluated the presence of CSDP immediately following CSP and biopsied the CSDP or the center of the mucosal defect without CSDP. The presence of the muscularis mucosa and any residual polyp in the biopsies was evaluated histologically. The primary outcome was the incidence of incomplete mucosal layer resection defined as the presence of muscularis mucosa or residual polyp in the biopsies. RESULTS: From August 2017 to October 2018, 188 patients were screened, and 357 polyps were included. CSDP was detected in 122/355 (34%) evaluated mucosal defects. Excluding five lesions requiring hemostasis immediately following CSP, 352 mucosal defects were biopsied. After excluding 102 biopsies containing normal mucosa, we evaluated 250 biopsies. The overall incidence of incomplete mucosal layer resection was 63% (159/250), 76% (68/90) with CSDP and 57% (91/159) without CSDP (P < 0.01). Both univariate and multivariate analyses showed that size (≥ 6 mm), resection time (≥ 5 s), and serrated lesions were risk factors for CSDP. CONCLUSIONS: Cold snare defect protrusion (CSDP), which was present with 36%, was a good indicator for incomplete mucosal layer resection. Even in nonCSDP polypectomies, 57% of the mucosal layer was not removed completely. Thus, CSP should be used for intra-epithelial lesions only, and careful pretreatment evaluation is recommended.

High incidence of head and neck cancers after endoscopic resection for esophageal cancer in younger patients.

BACKGROUND: Second cancers in patients with esophageal cancer (EC) are common and have a poor prognosis. We evaluated the incidence of second cancers at different sites by patients' ages when their index ECs were diagnosed. METHODS: This study included patients who underwent endoscopic resection for superficial EC at our hospital between September 1994 and September 2011. Patients' data, including sex, age at diagnosis, sequence of cancer incidence, cancer histology, and cancer site, were extracted from the cancer registry. RESULTS: Of 544 patients, 255 developed second cancers. Simultaneous head and neck cancers (HNCs) and other organ cancers (OCs) were, respectively, present in 15% (80/544) and 9.6% (52/544) of patients; and 30% (162/544) developed metachronous second cancers over a median follow-up period of 79.5 months (range 2-120), including 44 metachronous HNCs and 70 OCs. The cumulative incidence of metachronous HNCs was significantly higher in younger patients (< 60 years) than in older patients (≥ 60 years; P = 0.001), whereas the cumulative incidence of OCs was significantly higher in older patients than in younger patients (P = 0.03). CONCLUSIONS: The incidence of second HNC after index EC was higher in younger-onset patients than in older-onset patients. We suggest that younger patients with EC should be carefully monitored for early detection of second HNC.

Endoscopic full-thickness resection of gastric gastrointestinal stromal tumor: a Japanese case series.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are potentially malignant and are indicated for resection. The standard treatment for resectable GISTs is surgery, although endoscopic resection has been reported outside Japan. This study retrospectively analyzed the results of endoscopic resection of GISTs in Japan. METHOD: We identified patients with GISTs treated only by endoscopic resection in our institute between January 2016 and December 2018, and analyzed their clinical and pathological characteristics. RESULTS: During the study period, 8 GISTs were resected only by endoscopy: 7 were located in the upper third of the stomach and 1 in the middle. All were intraluminal growth type. Median (range) tumor diameter was 20 (10-35) mm. All tumors were resected en bloc with a median (range) operation time of 67.5 (50-166) min. Complete perforation occurred in 5 cases, but the serosa remained in 2 and the outer layer of the muscularis propria remained in 1. The defect was endoscopically closed with clip-and-endoloop purse-string suturing (n=3), simple endoclipping (n=2), or over-the-scope clipping (n=2), and 1 did not require closure because the outer longitudinal muscle was preserved. Oral feeding was commenced on postoperative day (POD) 3 (median; range 2-4), and the patient was discharged on POD 6 (median; range 4-11). No serious adverse event developed after the procedures. CONCLUSION: Endoscopic resection for selected cases of small intraluminal GISTs is feasible, making it a viable alternative treatment option to laparoscopic surgery.

Classification for invasion depth of esophageal squamous cell carcinoma using a deep neural network compared with experienced endoscopists.

BACKGROUND AND AIMS: Cancer invasion depth is a critical factor affecting the choice of treatment in patients with superficial squamous cell carcinoma (SCC). However, the diagnosis of invasion depth is currently subjective and liable to interobserver variability. METHODS: We developed a deep learning-based artificial intelligence (AI) system based on Single Shot MultiBox Detector architecture for the assessment of superficial esophageal SCC. We obtained endoscopic images from patients with superficial esophageal SCC at our facility between December 2005 and December 2016. RESULTS: After excluding poor-quality images, 8660 non-magnified endoscopic (non-ME) and 5678 ME images from 804 superficial esophageal SCCs with pathologic proof of cancer invasion depth were used as the training dataset, and 405 non-ME images and 509 ME images from 155 patients were selected for the validation set. Our system showed a sensitivity of 90.1%, specificity of 95.8%, positive predictive value of 99.2%, negative predictive value of 63.9%, and an accuracy of 91.0% for differentiating pathologic mucosal and submucosal microinvasive (SM1) cancers from submucosal deep invasive (SM2/3) cancers. Cancer invasion depth was diagnosed by 16 experienced endoscopists using the same validation set, with an overall sensitivity of 89.8%, specificity of 88.3%, positive predictive value of 97.9%, negative predictive value of 65.5%, and an accuracy of 89.6%. CONCLUSIONS: This newly developed AI system showed favorable performance for diagnosing invasion depth in patients with superficial esophageal SCC, with comparable performance to experienced endoscopists.

Pulley Traction-Assisted Colonic Endoscopic Submucosal Dissection: A Retrospective Case Series.

BACKGROUND AND STUDY AIMS: We have reported the usefulness of traction-assisted colorectal endoscopic submucosal dissection (TAC-ESD) to overcome the technical difficulty of colorectal ESD. However, the direction of traction is toward the anal side only. We retrospectively evaluate the safety and efficacy of "pulley" TAC-ESD. PATIENTS AND METHODS: We retrospectively analyzed patients diagnosed with colorectal polyps and treated by "pulley" TAC-ESD at Osaka International Cancer Institute from December 2017 to June 2018. RESULTS: During the study period, 79 patients with 81 lesions were treated by ESD, and 54 of these patients were treated by traction-assisted ESD. Among them, 7 underwent "pulley" traction-assisted ESD (6 men, 1 woman; age, 48-69 years), resulting in en bloc resection with no complications. This afforded good visibility of the submucosal layer in 6 patients, but it was not effective in the remaining patient with the muscle-retracting sign. CONCLUSION: The "pulley" method affords good visibility of the submucosal layer by changing the traction direction in cases that are difficult to manage by conventional traction-assisted ESD.

Natural history of early gastric cancer: series of 21 cases.

Background and study aims While knowledge of the natural history of early gastric cancer (EGC) may be useful in relevant clinical situations, few relevant reports are available. Therefore, we investigated the progression of EGC. We gathered data regarding 114 cases of EGC from 2005 to 2015 from a hospital cancer registry and analyzed 21 lesions that fulfilled five inclusion criteria. Deep progression was defined as submucosal invasion by a mucosal tumor and proper muscle invasion by a submucosal tumor. Lateral progression was defined as ≥ 20 % increase in size. During median follow-up of 23 months, one of 18 mucosal tumors showed deep progression and six showed lateral progression. Of three submucosal tumors, two showed deep progression and three showed lateral progression. Our study suggests that a certain proportion of mucosal cancers can lie dormant for several years. Further large-scale studies in a multicenter setting should overcome the limitations of this study.

Impact of age at diagnosis of head and neck cancer on incidence of metachronous cancer.

BACKGROUND: Metachronous cancer in patients with head and neck cancer (HNC) is common and is associated with a poor prognosis. We aimed to evaluate the incidence of metachronous cancer at different sites according to age at diagnosis of index HNC. METHODS: We collected data on 2011 patients with oral cancer, oropharynx cancer, hypopharyngeal cancer, and laryngeal cancer as index cancers using the Osaka International Cancer Institute Cancer Registry database between 2005 and 2016. Among these, we analyzed 1953 patients after excluding 5 patients who were not followed-up and 53 patients with simultaneous multiple index cancers. We evaluated the cumulative incidence of metachronous cancer in the esophagus, lung, and other sites according to age at diagnosis of the index HNC using the Kaplan-Meier method. Multivariate logistic regression analysis was performed to identify factors that influenced the incidence of metachronous cancers following HNC. RESULTS: The cumulative incidence of metachronous esophageal cancer in young patients (< 65 years) was significantly higher than that in old patients (≥ 65 years) (12.1% vs 8.5% at 5 years, and 16.5% vs 11.2% at 10 years; p = 0.015). On the other hand, the cumulative incidence of the other cancers in young patients was significantly lower than that in old patients (7.8% vs 12.2% at 5 years, and 13.9% vs 15.3% at 10 years; p = 0.017). The cumulative incidence of lung cancer was not significance according to age at diagnosis of the index HNC. In the multivariate analysis, histological type (squamous cell carcinoma) and lesion location (hypopharynx and larynx) were independently associated with metachronous cancers. Moreover, age at diagnosis of the index HNC (< 65 years), histological type (squamous cell carcinoma) and lesion location (hypopharynx) were significant predictors of metachronous esophageal cancer incidence and lesion location (hypopharynx) was a significant predictor of metachronous lung cancer incidence. CONCLUSION: Risk stratification of metachronous cancers with age and other predictors may help to properly manage patients with HNC. TRIAL REGISTRATION: The present study is a non-intervention trial.