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Shigeki Minami,1 Chika Sakimura,1 Junji Irie,2 Yukiko Tokai,3 Hitoshi Okubo,4 Tsuyoshi Ohno5 1Department of Breast and Endocrine Surgery, Nagasaki Harbor Medical Center, Nagasaki 850-8555, Japan; 2Department of Pathology, Nagasaki Harbor Medical Center, Nagasaki, Japan; 3Department of Breast Surgery, Imamura Women’s Clinic, Nagasaki, Japan; 4Okubo Breast Clinic, Nagasaki, Japan; 5Ohno Breast and Thyroid Clinic, Nagasaki, JapanCorrespondence: Shigeki MinamiDepartment of Breast and Endocrine Surgery, Nagasaki Harbor Medical Center, 6-39 Shinchi-machi, Nagasaki 850-8555, JapanTel +81-95-822-3251Fax +81-95-826-8798Email br9-origam@umin.netBackground: The axillary lymph node status is an important prognostic factor of breast cancer. This study explores the predictive factors for sentinel lymph node (SLN) metastasis among the preoperative clinicopathological features, including impaired glucose tolerance (IGT).Methods: This study comprised patients diagnosed with breast cancer who underwent surgery at Nagasaki Harbor Medical Center between April 2014 and December 2019. The factors assessed using univariate and multivariate analyses were the clinicopathological data of these cancers, including the patient age, gender, menstrual status, breast or ovarian cancer family history, body mass index, glycosylated hemoglobin, clinical tumor size, nipple-tumor distance (NTD), tumor histology, histological grade, node status, estrogen receptor, progesterone receptor, human epidermal growth factor receptor type 2 status, and Ki67 labeling index.Results: In the cohort of 313 cases, the ratio of SLN metastasis was 17.3%. A univariate analysis found that the tumor size, NTD, IGT, and clinical tumor stage were associated with SLN metastasis. In a multivariable analysis, the tumor size, NTD, and IGT were associated with SLN metastasis. The receiver operating characteristic curve showed a sensitivity and specificity of 61.1% and 65.6%, respectively, at a cut-off of 1.7 cm for the tumor size (area under the curve [AUC]: 0.664; 95% confidence interval: 0.592– 0.736), and a sensitivity and specificity of 60.4% and 62.9%, respectively, at a cut-off of 2.0 cm for NTD (AUC: 0.651; 95% confidence interval: 0.571– 0.731) to predict the risk of SLN metastasis.Conclusion: T1 and T2 breast cancer patients with a larger tumor size, tumor located closer to the nipple, and IGT have a higher risk of SLN metastases than others.Keywords: breast cancer, sentinel lymph node metastasis, predictive factor, nipple-tumor distance, impaired glucose tolerance

Background: Artificial intelligence (AI) has made remarkable progress in image recognition using deep learning systems. It has been used to detect esophageal squamous cell carcinoma (ESCC); however, none of the previous reports were investigations in a clinical setting, being retrospective in design. We therefore conducted this trial to determine how AI can help endoscopists detect ESCC in a clinical setting., Methods: This was a prospective, single-center, exploratory, and randomized controlled trial. High risk patients with ESCC undergoing screening or surveillance esophagogastroduodenoscopy were enrolled and randomly assigned to either the AI or control groups. In the AI group, the endoscopists watched both the AI monitor that detected ESCC with annotation and the normal monitor simultaneously; in the control group, the endoscopists watched only the normal monitor. In both groups, the endoscopists observed the esophagus using white-light imaging (WLI), followed by narrow-band imaging (NBI), then iodine staining. The primary end point was the enhanced detection rate of ESCC by nonexperts using AI. The detection rate was defined as the ratio of WLI/NBI-detected ESCCs to all ESCCs detected by iodine staining., Results: 320 patients were included in the analysis. The detection rate of ESCC among nonexperts was 47% in the AI group and 45% in the control group ( P = 0.93), with no significant difference, which was similarly found for experts (87% vs. 57%; P = 0.20) and all endoscopists (57% vs. 50%; P = 0.70)., Conclusions: This study could not demonstrate an improvement in the esophageal cancer detection rate using the AI diagnostic support system for ESCC., Competing Interests: T. Hirasawa has received lecture fees from AI Medical Service Inc. outwith this study. T. Tada is a shareholder in AI Medical Service Inc. E. Nakao, T. Yoshio, Y. Kato, K. Namikawa, Y. Tokai, S. Yoshimizu, Y. Horiuchi, A. Ishiyama, N. Kurihara, N. Ishizuka, R. Ishihara, and J. Fujisaki declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background and Study Aim: Endoscopic resection (ER) of esophageal squamous cell carcinoma (ESCC) is an organ-preserving treatment; however, heterochronic carcinomas are often encountered. Most patients are treated using ER; however, for some, this is inadequate and requires additional treatment. We sought to identify the characteristics and frequency of lesions at high risk of metastasis during surveillance based on Lugol-voiding lesion (LVL) grading and esophagogastroduodenoscopy (EGD) intervals., Methods: Of the 1301 patients who underwent ER, 956 underwent surveillance EGD at our hospital for at least 1 year (median, 59 months). We analyzed identified multiple ESCCs to reveal the characteristic of high-metastasis-risk lesions, which was defined ESCC with submucosal or lymphovascular invasion., Results: In the 956 patients, 444 multiple ESCCs were identified in 216 patients and the cumulative incidence of multiple ESCCs was 15.4% and 22.9% at 3 and 5 years, respectively, while for high-risk lesions, it was 1.0% and 1.8%. The risk factors for high-metastasis-risk lesions were being female (odds ratio (OR):5.58, 95% confidence interval (CI):1.96-15.9), lesions located in the cervical/upper thoracic esophagus (OR: 4.81, 95% CI:1.80-12.8), and the presence of submucosal tumor (SMT)-like marginal elevation (OR:65.4, 95% CI:11.0-390). No significant differences in the frequency of high-risk lesions were found based on LVL grade at any EGD intervals., Conclusion: During endoscopic surveillance, attention should be given to the cervical/upper thoracic esophagus and lesions with SMT-like marginal elevation. The frequency of high-metastasis-risk lesions was not different by LVL grade or EGD intervals., Competing Interests: Declarations Conflicts of interest There are no conflicts of interest with regard to publication of this study. Ethical statement The study was conducted in accordance with the 1964 Declaration of Helsinki and subsequent amendments and was approved by the Institutional Review Board of Cancer Institute Hospital (approval number:2023-GB-001)., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: The effectiveness of esophagogastroduodenoscopy (EGD) screening in cohorts with low Helicobacter pylori prevalence is unknown. This study aimed to develop an optimally efficient EGD screening strategy for detecting H. pylori-naïve gastric neoplasms (HpNGNs)., Methods: EGD data of 12 institutions from 2016 to 2022 were retrospectively analyzed. Age-related HpNGN prevalence, tumor growth rate, missing rate, and detection threshold size were calculated from the databases. Subsequently, using clinical data, a novel mathematical model that simultaneously simulated demographic changes and HpNGN detection was developed. Screening strategies using different starting ages (40/45/50 years) and intervals (2/5/10 years) were also compared. The detection rates of all tumors occurring within the virtual cohort and number-needed-to-test (NNT) were measured as outcomes., Results: Data of 519,368 EGDs and 97 HpNGNs (34 pure signet ring cell carcinomas, 26 gastric adenocarcinomas of the fundic gland type, 30 foveolar gastric adenoma-Raspberry type, and seven undifferentiated-type cancer cases) were analyzed. A virtual cohort with a 70-year time horizon was used to simulate the occurrence, growth, and detection of 346,5836 people. Among the strategies with detection rate > 50%, the screening strategy with a 5-year interval starting at 45 years of age had the lowest NNT. Adopting this strategy, most HpNGNs were detected at < 20 mm in size, and the deep submucosal invasion rate was less than 30%., Conclusions: A mathematical simulation model revealed that screening every 5 years starting at 45 years of age could efficiently assist in identifying HpNGNs at an early stage., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: Little is known about prognostic factors for patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer. Therefore, this study aimed to identify such prognostic factors., Methods: We retrospectively evaluated the long-term outcomes and prognostic factors of 143 patients 85 years or older undergoing endoscopic submucosal dissection for early gastric cancer at a single-center between October 2005 and September 2020. Using the Kaplan-Meier method and a Cox proportional hazards regression model, we examined the relationships of patient characteristics and endoscopic curability (additional gastrectomy recommended [eCuraC-2] or not recommended) with overall survival., Results: The median age of the patients was 86 years, and most patients were men (65%). The eCuraC-2 rate was 14.7%. During the follow-up period, 55 patients died; however, only two patients died due to gastric cancer. The 3-year and 5-year overall survival rates were 91.5% and 74.7%, respectively. Male sex (hazard ratio, 2.23; 95% confidence interval, 1.16-4.30), American Society of Anesthesiologists Physical Status of 3 (hazard ratio, 2.57; 95% confidence interval, 1.32-4.99), body mass index < 18.9 kg/m 2 (hazard ratio, 2.21; 95% confidence interval, 1.11-4.40), and eCuraC-2 (hazard ratio, 3.04; 95% confidence interval, 1.37-6.75) were identified as independent prognostic factors. Moreover, patients with eCuraC-2 had significantly more poor prognostic factors than those who did not., Conclusions: The decision to perform endoscopic submucosal dissection for patients with the aforementioned prognostic factors should be carefully considered because follow-up without endoscopic submucosal dissection is possible., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Distinguishing between intramucosal cancer and submucosal invasive cancer is vital for optimal treatment selection for patients with superficial nonampullary duodenal adenocarcinoma (SNADAC); however, standard diagnostic systems for diagnosing invasion depth are as yet undetermined., Methods: Of 205 patients with SNADAC who underwent treatment at our institution between 2006 and 2022, 188 had intramucosal cancer and 17 had submucosal invasive cancer. The clinical, endoscopic, and pathological features used in the preoperative diagnosis of invasion depth and the diagnostic performance of endoscopic ultrasonography (EUS) were retrospectively analyzed in 85 patients., Results: The oral side of the papilla tumor location, protruded or mixed macroscopic type, and moderately-to-poorly differentiated adenocarcinoma based on biopsy specimens were significantly more frequent in submucosal invasive cancer than in intramucosal cancer (88% vs. 48%; 94% vs. 42%; 47% vs. 0%, respectively). From the relationship between the endoscopic features and the submucosal invasive cancer incidence, submucosal invasion risk was stratified as: (i) low-risk (risk, 2%), all lesions located on the anal side of the papilla and superficial macroscopic type on the oral side of the papilla; and (ii) high-risk (risk, 23%), protruded or mixed macroscopic type on the oral side of the papilla. Based on the biopsy specimens, all eight patients with moderately-to-poorly differentiated adenocarcinoma had submucosal invasive cancer. Furthermore, EUS was not associated with invasion depth's diagnostic accuracy improvements., Conclusion: Optimal treatment indications for SNADAC can be selected based on the risk factors of submucosal invasion by tumor location, macroscopic type, and biopsy diagnosis., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background: In Japan, the standard management of Barrett's esophageal adenocarcinoma after endoscopic submucosal dissection involves follow-up; however, multifocal synchronous/metachronous lesions are sometimes observed after endoscopic submucosal dissection. Risk stratification of multifocal cancer facilitates appropriate treatment, including eradication of Barrett's esophagus in high-risk cases; however, no effective risk stratification methods have been established. Thus, we identified the risk factors for multifocal cancer and explored risk-stratified treatment strategies for residual Barrett's esophagus., Methods: We retrospectively reviewed the data of 97 consecutive patients with superficial Barrett's esophageal adenocarcinomas who underwent curative resection with endoscopic submucosal dissection. Multifocal cancer was defined by the presence of synchronous/metachronous lesions during follow-up. We used Cox regression analysis to identify the risk factors for multifocal cancer and subsequently analyzed differences in cumulative incidences., Results: The cumulative incidences of multifocal cancer at 1, 3, and 5 years were 4.4%, 8.6%, and 10.7%, respectively. Significant risk factors for multifocal cancer were increased circumferential and maximal lengths of Barrett's esophagus. The cumulative incidences of multifocal cancer at 3 years were lower for patients with circumferential length < 4 cm and maximal length < 5 cm (2.9% and 1.2%, respectively) than for patients with circumferential length ≥ 4 cm and maximal length ≥ 5 cm (51.5% and 49.1%, respectively)., Conclusions: Risk stratification of multifocal cancer using length of Barrett's esophagus was effective. Further multicenter prospective studies are needed to substantiate our findings., (© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background: The incidence of Barrett's esophageal adenocarcinoma (BEA) is increasing, and endoscopic submucosal dissection (ESD) has been frequently performed for its treatment. However, the differences between the characteristics and ESD outcomes between short- and long-segment BEA (SSBEA and LSBEA, respectively) are unclear. We compared the clinicopathological characteristics and short- and long-term outcomes of ESD between both groups., Methods: We retrospectively reviewed 155 superficial BEAs (106 SSBEAs and 49 LSBEAs) treated with ESD in 139 patients and examined their clinicopathological features and ESD outcomes. SSBEA and LSBEA were classified based on whether the maximum length of the background mucosa of BEA was < 3 cm or ≥ 3 cm, respectively., Results: Compared with SSBEA, LSBEA showed significantly higher proportions of cases with the macroscopically flat type (36.7% vs. 5.7%, p < 0.001), left wall location (38.8% vs. 11.3%, p < 0.001), over half of the tumor circumference (20.4% vs. 1.9%, p < 0.001), and synchronous lesions (17.6% vs. 0%, p < 0.001). Compared with SSBEA, regarding ESD outcomes, LSBEA showed significantly longer resection duration (91.0 min vs. 60.5 min, p < 0.001); a lower proportion of submucosal invasion (14.3% vs. 29.2%, p = 0.047), horizontal margin negativity (79.6% vs. 94.3%, p = 0.0089), and R0 resection (69.4% vs. 86.8%, p = 0.024); and a higher proportion of post-procedural stenosis cases (10.9% vs. 1.9%, p = 0.027). The 5-year cumulative incidence of metachronous cancer in patients without additional treatment was significantly higher for LSBEA than for SSBEA (25.0% vs. 0%, p < 0.001)., Conclusions: The clinicopathological features of LSBEA and SSBEA and their treatment outcomes differed in many aspects. As LSBEAs are difficult to diagnose and treat and show a high risk of metachronous cancer development, careful ESD and follow-up or eradication of the remaining BE may be required., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The effect of Helicobacter pylori (H.pylori) eradication therapy on mixed-histological-type gastric cancer remains unclear. This study aimed to clarify the effect of H. pylori eradication therapy on mixed-histological-type early gastric cancer using endoscopic and histological findings., Methods: This single-center, retrospective study included patients with mixed-histological-type gastric cancer who underwent endoscopic submucosal dissection at the Cancer Institute Hospital. We compared detailed magnifying endoscopy with narrow-band imaging findings between eradicated and non-eradicated groups of patients with differentiated-type- and undifferentiated-type-predominant cancers. Subsequently, we performed histological evaluations of the non-cancerous epithelium covering differentiated-type components., Results: A total of 124 patients with mixed-type early gastric cancer were enrolled (eradicated group: 62 differentiated-type-predominant cancer patients and 8 undifferentiated-type-predominant cancer patients; non-eradication group: 40 differentiated-type-predominant cancer patients and 14 undifferentiated-type-predominant cancer patients). Regarding differentiated-type-predominant cancer, differentiated-type findings were detected in all patients in eradicated and non-eradicated groups. The difference in the detection rate of undifferentiated-type findings between both groups was not significant in differentiated-type-predominant cancer patients. In differentiated-type-predominant cancers, the percentage of non-cancerous epithelium covering differentiated-type components was higher in the eradicated group than in the non-eradicated group (median: 60% vs. 40%, p < 0.001)., Conclusions: Although the pathological findings of differentiated-type-predominant cancer were affected by H. pylori eradication, eradication did not affect the diagnosis of differentiated-type-predominant early gastric cancer using magnifying endoscopy with narrow-band imaging. ME-NBI is useful for the early detection of D-MIX EGCs and diagnosis of histological types during endoscopy, regardless of whether H. pylori eradication therapy has been administered., (© 2023. The Author(s).)

Patients with malignant esophageal fistulas often experience dysphagia and infection, resulting in poor prognoses. Self-expandable metallic stent (SEMS) placement is a palliative treatment option; however, its efficacy and safety are unclear. We aimed to determine the efficacy and safety of SEMS placement for malignant esophageal fistulas. We retrospectively investigated patients who underwent SEMS placement for malignant esophageal fistulas between 2013 and 2022 at the Cancer Institute Hospital. Dysphagia scores (DSs) before and after SEMS placement, adverse events, and overall survival from SEMS placement until death were evaluated. A total of 17 patients underwent SEMS placement, including 12 and 5 patients with esophageal and lung cancers, respectively. Prior treatments included chemoradiotherapy ( n = 11), radiotherapy ( n = 4), and chemotherapy ( n = 4); two patients underwent palliative radiotherapy after chemotherapy. All procedures were technically successful. After SEMS placement, 14 (82.4%) patients were able to consume semisolid or solid food (DS ≤ 2). Major adverse events were encountered in only one case. The median survival time after SEMS placement was 71 days (range 17-247 days). SEMS placement allowed most patients to resume oral intake with a low rate of major adverse events. SEMS placement is a reasonable palliative treatment option for patients with malignant fistulas who have poor prognoses.

We herein report two cases of early esophageal adenocarcinoma derived from non-Barrett's columnar epithelium. Both patients, a 65-year-old woman and 60-year-old man, had elevated lesions on white-light imaging. Magnifying endoscopy revealed slightly irregular surface and vessel patterns, and both patients were successfully treated with endoscopic submucosal dissection. Histopathologically, both lesions comprised of well-differentiated gastric mucin phenotype adenocarcinoma. One lesion was accompanied by ectopic gastric mucosa, but the other was speculated to be ectopic gastric mucosa according to the tumor locus at the upper thoracic esophagus. Despite its rarity, endoscopists should consider the existence of adenocarcinoma derived from non-Barrett's columnar epithelium.

Background and Aim: Helicobacter pylori ( H. pylori ) eradication has become popular as it prevents the development of gastric cancer. There have been no comprehensive studies on advanced gastric cancer (AGC) after eradication; thus, the clinical characteristics remain unclear. This study aimed to compare the characteristics of AGC after eradication and with current H. pylori infection and evaluate the esophagogastroduodenoscopy (EGD) follow-up after eradication., Methods: This single-center, retrospective study included 261 consecutive patients diagnosed with AGC through EGD. The patients were grouped based on their H. pylori status: eradication ( n  = 48) and infection ( n  = 213) groups. Univariate analysis was conducted to compare clinicopathological characteristics between groups. The clinical course of the eradication group was analyzed by dividing the patients into three groups according to the interval from the last EGD until AGC detection: short-interval (<1 year), intermediate-interval (2-3 years), and long-interval (4-5 years) groups., Results: The radical resection (R0) rate was higher in the eradication group. In surgical cases, the median tumor diameter was shorter in the eradication group. Analysis of EGD surveillance after eradication in 36 available cases showed that 24 (66.7%) were detected within 5 years after eradication, and 3 (8.3%) were diagnosed as AGC > 20 years after eradication. The R0 rates in the short-, intermediate-, and long-interval groups were 83.3%, 71.4%, and 60%, respectively., Conclusions: AGC after eradication was more often detected at the phase in which R0 resection was possible. EGD follow-up with tight intervals of at least 5 years after eradication is advisable., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Helicobacter pylori (HP) is a major etiologic driver of diffuse-type gastric cancer (DGC). However, improvements in hygiene have led to an increase in the prevalence of HP-naïve DGC; that is, DGC that occurs independent of HP. Although multiple genomic cohort studies for gastric cancer have been conducted, including studies for DGC, distinctive genomic differences between HP-exposed and HP-naïve DGC remain largely unknown. Here, we employed exome and RNA sequencing with immunohistochemical analyses to perform binary comparisons between 36 HP-exposed and 27 HP-naïve DGCs from sporadic, early-stage, and intramucosal or submucosal tumor samples. Among the samples, 33 HP-exposed and 17 HP-naïve samples had been preserved as fresh-frozen samples. HP infection status was determined using stringent criteria. HP-exposed DGCs exhibited an increased single nucleotide variant burden (HP-exposed DGCs; 1.97 [0.48-7.19] and HP-naïve DGCs; 1.09 [0.38-3.68] per megabase; p = 0.0003) and a higher prevalence of chromosome arm-level aneuploidies (p < 0.0001). CDH1 was mutated at similar frequencies in both groups, whereas the RHOA-ARHGAP pathway misregulation was exclusive to HP-exposed DGCs (p = 0.0167). HP-exposed DGCs showed gains in chromosome arms 8p/8q (p < 0.0001), 7p (p = 0.0035), and 7q (p = 0.0354), and losses in 16q (p = 0.0167). Immunohistochemical analyses revealed a higher expression of intestinal markers such as CD10 (p < 0.0001) and CDX2 (p = 0.0002) and a lower expression of the gastric marker, MUC5AC (p = 0.0305) among HP-exposed DGCs. HP-naïve DGCs, on the other hand, had a purely gastric marker phenotype. This work reveals that HP-naïve and HP-exposed DGCs develop along different molecular pathways, which provide a basis for early detection strategies in high incidence settings. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Background: An association between specific endoscopic findings and high-grade dysplasia/carcinoma in superficial nonampullary duodenal epithelial tumors ≤ 5 mm in size has not been reported. We sought to identify the endoscopic findings associated with high-grade dysplasia/carcinoma in patients with superficial nonampullary duodenal epithelial tumors ≤ 5 mm., Methods: We retrospectively assessed the data of 84 patients (88 lesions; low-grade dysplasia: n = 35, high-grade dysplasia/carcinoma: n = 53) with superficial nonampullary duodenal epithelial tumors who underwent initial treatment at a single center (from July 2009 to April 2021). All the patients had lesions sized ≤ 5 mm. We assumed that the endoscopic findings were independently associated with high-grade dysplasia/carcinoma and determined the accuracy, sensitivity, and specificity of a combination of independent factors for diagnosing high-grade dysplasia/carcinoma and low-grade dysplasia., Results: Multivariate logistic regression of significant factors in the univariate analysis revealed that lesions with depressed morphology (odds ratio: 23.9, 95% confidence interval: 2.8-204.2; p = 0.0037) and a reddish color (odds ratio: 175.7, 95% confidence interval: 11.4-2697.1; p = 0.0002) were independently associated with high-grade dysplasia/carcinoma. McNemar's test revealed that combining the macroscopic type and color provided significantly higher sensitivity for diagnosing high-grade dysplasia/carcinoma than color alone (98.1%, 95% confidence interval: 90.1-99.7 vs. 71.7%, 95% confidence interval: 58.4-82.0; p = 0.0002)., Conclusions: Reddish and depressed-type lesions before treatment were associated with high-grade dysplasia/carcinoma. Combining the macroscopic type and color can help detect high-grade dysplasia/carcinoma. These findings could help clinicians determine the best therapeutic strategy for patients with smaller (≤ 5 mm) superficial nonampullary duodenal epithelial tumors in clinical settings., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited., Methods: Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months)., Results: In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively., Conclusions: Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated., (© 2021 Japan Gastroenterological Endoscopy Society.)

Background: No studies have compared the performance of microvascular and microsurface patterns alone with their combination in patients undergoing magnifying endoscopy with narrow-band imaging for diagnosing gastric cancer. This study aimed to clarify the differences in diagnostic performance among these methods., Methods: Thirty-three participating endoscopists who had received specialized training in magnifying endoscopy evaluated the microvascular and microsurface patterns of images of 106 cancerous and 106 non-cancerous lesions. If classified as "irregular," the lesion was diagnosed as gastric cancer. To evaluate diagnostic performance, we compared the diagnostic accuracy, sensitivity, and specificity of these methods., Results: Performance-related items did not differ significantly between microvascular and microsurface patterns. However, the diagnostic accuracy and sensitivity were significantly higher when using a combination of these methods than when using microvascular (82.1% [76.4-86.7] vs. 76.4% [70.3-81.6] and 69.8% [60.5-77.8] vs. 63.2% [53.7-71.8]; P < 0.001 and P = 0.008, respectively) or microsurface (82.1% [76.4-86.7] vs. 73.6% [67.3-79.1] and 69.8% [60.5-77.8] vs. 52.8% [43.4‒62.1]; both, P < 0.001) patterns alone. The additive effect on diagnostic accuracy and sensitivity was 5.7‒8.6% and 6.6‒17.0%, respectively., Conclusions: We demonstrate the superiority of the combination of microvascular and microsurface patterns over microvascular or microsurface patterns alone for diagnosing gastric cancer. Our data support the use of the former method in clinical practice. Although a major limitation of this study was its retrospective, single-center design, our findings may help to improve the diagnosis of gastric cancer., (© 2022. The Author(s).)

Background and study aims  Management strategies for sporadic non-ampullary duodenal adenoma with low-grade dysplasia (LGD) are not well established. This study aimed to analyze progression factors and determine suitable treatment strategies for LGD lesions. Patients and methods  We retrospectively analyzed consecutive LGD lesions (n = 125) in patients followed up for ≥ 6 months (median, 45 months) and evaluated the changes in clinicopathological features during follow-up. All LGD lesions were classified into two groups: stable LGD (no increase or < 5 mm increase in tumor size, with unchanged histological dysplasia grade) and progressive LGD (≥ 5 mm increase in tumor size and/or progression to high-grade dysplasia or adenocarcinoma). Results  Eighty-six LGD were classified as stable and 39 as progressive. Location on the oral side of the papilla of Vater, large initial tumor size ( ≥ 10 mm), macroscopically complex type, red color, and nodularity were significantly frequent in progressive LGD than in stable LGD. In multivariate analysis, large initial tumor size (odds ratio [OR], 10.2; 95 % confidence interval [CI], 3.3-32.1; P  < 0.001) and location on the oral side of the papilla of Vater (OR: 1.8, 95 % CI: 1.4-12.5; P  = 0.012) were significant factors for progression. Moreover, initial tumor size < 5 mm rarely progressed (0%-3.9 %); however, initial tumor size ≥ 20 mm and 10-19 mm located on the oral side of the papilla of Vater had a high-risk progression rate (75.0-85.7 %). Conclusions  According to the risk stratification of progression factors by initial tumor size and location, we can determine suitable treatment indications for LGD lesions., Competing Interests: Competing interests The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Aim: The risk factors for lymph node metastasis (LNM) of duodenal neuroendocrine tumors (DNETs) are not well identified, and a definitive standard of treatment for DNETs has not been established. In this study, we aimed to identify the risk factors for LNM and establish the indication of local resection for DNETs., Methods: We retrospectively reviewed 55 patients with 60 non-ampullary and nonfunctional DNETs. We evaluated the risk factors for LNM and compared the outcomes between endoscopic resection (ER) for DNETs <5 mm and laparoscopy and endoscopy cooperative surgery (LECS) for DNETs ≥5 mm., Results: LNM was present in four (8.7%) patients. Univariate analysis revealed that tumor size ≥10 mm, positive lymphovascular invasion (LVI), and 0-Is morphology were significantly associated with LNM ( P  = 0.008, P  = 0.037, and P  = 0.045, respectively). ER and LECS were performed for 18 and 11 DNETs, respectively. All lesions treated with ER or LECS were confined to the submucosal layer. The median tumor size was 3 mm in ER and 6 mm in LECS. Although there was no significant difference in the R0 (no residual tumor) resection rate, R0 resection was completely achieved in the LECS. No significant differences were observed in terms of complication rates. No recurrence was observed in any of the groups., Conclusions: Tumor size ≥10 mm, positive LVI, and 0-Is morphology were significant risk factors for LNM. We demonstrated that ER is feasible and could be safely applied for DNETs <5 mm, and LECS could be applied for DNETs 5-10 mm in size., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Although endocytoscopy (EC) with narrow-band imaging (NBI) is effective in diagnosing gastric cancer, no diagnostic system has been validated. We explored a specific diagnostic system for gastric cancer using EC with NBI., Methods: Equal numbers of images from cancerous and noncancerous areas (114 images each) were assessed by endoscopists with (development group: 33) and without (validation group: 28) specific training in magnifying endoscopy with NBI. Microvascular and microsurface patterns (MS) in each image were evaluated. Lesions were diagnosed as cancerous when patterns were deemed "irregular." The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of a diagnosis according to patterns on EC with NBI (microvascular pattern [MV] alone, MS alone, and both) were evaluated and compared between groups to determine the diagnostic performance., Results: In the development and validation groups, diagnoses based on the MV alone had significantly higher accuracy (91.7% vs. 76.3%, p < 0.0001 and 92.5% vs. 67.5%, p < 0.0001, respectively) and sensitivity (88.6% vs. 68.3%, p < 0.0001 and 89.5% vs. 38.6%, p < 0.0001, respectively) than those based on the MS alone. In both groups, there were no significant differences in diagnostic accuracy between using the MV alone and both patterns., Discussion/conclusion: Evaluation of the MV alone is a simple and accurate diagnostic method for gastric cancer. This system could find widespread applications in clinical practice., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Introduction: We aimed to investigate the safety and efficacy of self-expandable metallic stent (SEMS) placement in patients with prior radiotherapy (RT) using the Niti-S stent, which is characterized by low radial force, in comparison to patients without prior RT., Methods: A consecutive series of 83 patients who were treated by SEMS placement using Niti-S stent for severe malignant esophageal obstruction or fistula were enrolled. The adverse event rates and efficacy were retrospectively compared between patients with/without prior RT before SEMS placement (RT group [n = 32] versus non-RT group [n = 51])., Results: The incidence rate of major adverse events in the RT group was 6.3% and was not significantly different from that in the non-RT group (5.9%, p = 0.95). Among the RT group, 84.4% were able to resume oral intake within a median of 2 days. Among the patients with fistula, 78.6% could resume oral intake and survive for 73 days after SEMS placement. Cox proportional hazard regression analysis identified significant factors affecting overall survival to be prior RT (hazard ratio [HR]: 1.96), low performance status (HR: 3.87), and subsequent anticancer treatment after SEMS placement (HR: 0.41). However, compared to the non-RT group, the RT group had received longer duration of anticancer treatment before SEMS placement and a lower rate of subsequent anticancer treatment after SEMS placement., Conclusions: With the Niti-S stent, the incidence of major adverse events was sufficiently low even for patients after RT. SEMS with low radial force would be an effective palliative treatment option for patients, regardless of prior RT., (© 2022 S. Karger AG, Basel.)

Background: It is known that an esophagus with multiple Lugol-voiding lesions (LVLs) after iodine staining is high risk for esophageal cancer; however, it is preferable to identify high-risk cases without staining because iodine causes discomfort and prolongs examination times. This study assessed the capability of an artificial intelligence (AI) system to predict multiple LVLs from images that had not been stained with iodine as well as patients at high risk for esophageal cancer., Methods: We constructed the AI system by preparing a training set of 6634 images from white-light and narrow-band imaging in 595 patients before they underwent endoscopic examination with iodine staining. Diagnostic performance was evaluated on an independent validation dataset (667 images from 72 patients) and compared with that of 10 experienced endoscopists., Results: The sensitivity, specificity, and accuracy of the AI system to predict multiple LVLs were 84.4 %, 70.0 %, and 76.4 %, respectively, compared with 46.9 %, 77.5 %, and 63.9 %, respectively, for the endoscopists. The AI system had significantly higher sensitivity than 9/10 experienced endoscopists. We also identified six endoscopic findings that were significantly more frequent in patients with multiple LVLs; however, the AI system had greater sensitivity than these findings for the prediction of multiple LVLs. Moreover, patients with AI-predicted multiple LVLs had significantly more cancers in the esophagus and head and neck than patients without predicted multiple LVLs., Conclusion: The AI system could predict multiple LVLs with high sensitivity from images without iodine staining. The system could enable endoscopists to apply iodine staining more judiciously., Competing Interests: Tomohiro Tada is a shareholder in AI Medical Service, Inc. All other authors declare that they have no conflicts of interest., (Thieme. All rights reserved.)

Background: Anastomotic leak is a potentially life-threatening complication following esophageal cancer surgery. In this study, we aimed to clarify the efficacy of endoscopic filling with polyglycolic acid (PGA) sheets and fibrin glue for anastomotic leak after esophageal cancer surgery., Methods: Consecutive patients who underwent endoscopic filling with PGA sheets and fibrin glue for anastomotic leak after esophageal cancer surgery between August 2014 and January 2020 were included in the study, with its efficacy retrospectively reviewed. We performed endoscopic filling using two methods: (1) filling the fistula with PGA sheets, followed by the application of a fibrinogen and thrombin solution (conventional method) and (2) filling the fistula with PGA sheets pre-soaked in a fibrinogen solution, followed by the application of a thrombin solution (pre-soak method)., Results: A total of 14 patients underwent endoscopic filling procedures within the study period. The endoscopic filling procedures were successfully performed in all cases and no adverse events associated with the procedures were observed. Fistula closure was obtained in 10 (71%) cases. In the 10 successful cases, the median number of procedures was 1 (range 1-3) and the median time from the first procedure to oral intake was 7.5 days (range 4-36 days). The success rate of the pre-soak method was significantly higher than that of the conventional method (90% vs. 25%, P = 0.041)., Conclusions: Endoscopic filling with PGA sheets and fibrin glue is a safe and effective treatment for the closure of an anastomotic leak. The pre-soak method can achieve successful endoscopic filling.

Background and Aim: Helicobacter pylori antibody levels in the blood are currently measured using an ELISA. In April 2016, FUJIFILM Wako Pure Chemical Corporation launched the "l-type Wako Helicobacter pylori antibody J" test, which is based on the latex agglutination turbidimetric immunoassay. In this study, we investigated the usefulness of the Wako test., Methods: We measured H. pylori antibody levels using both the ELISA and Wako test in 180 patients who underwent upper gastrointestinal endoscopy at our hospital between September 2017 and February 2019. Ninety patients were infected with H. pylori . We calculated the diagnostic accuracy, sensitivity, and specificity of each test and the concordance rate between the ELISA and Wako test. If lower limits of 90% confidence intervals (CIs) for each diagnostic validity exceeded the 85% threshold, the usefulness of the diagnostic test was confirmed., Results: The diagnostic accuracy, sensitivity, and specificity were 94.4% (90% CI, 90.8-97.0%), 94.4% (90% CI, 88.7-97.8%), and 94.4% (90% CI, 88.7-97.8%), respectively, when the Wako test was used, and 94.4% (90% CI, 90.8-97.0%), 88.9% (90% CI, 81.9-93.8%), and 100% (90% CI, 96.0-100%), respectively, when the ELISA was used. The concordance rate between the two tests was high ( κ  = 0.8444)., Conclusions: We confirmed the usefulness of the Wako test, especially when screening for H. pylori infection, due to its high sensitivity., (© 2021 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: l-Menthol has smooth muscle-relaxing and antiperistaltic effects. We examined its effectiveness against peristalsis resumption during endoscopic submucosal dissection (ESD) of gastric tumors., Methods: We retrospectively examined clinical data of 485 patients (501 lesions) who underwent ESD for upper gastrointestinal tumors in 2017. We included 119 patients (127 lesions) in whom peristaltic movement resumed during ESD and l-menthol was applied; 366 patients (374 lesions) without l-menthol application were used as controls. Video recordings were reviewed to determine whether l-menthol suppressed peristalsis resumption., Results: In cases with l-menthol application, 2 (2.9%), 36 (14.3%), and 89 (71.2%) lesions were found in the upper (U), middle (M), and lower (L) regions, respectively. In the control group, the corresponding values were 66 (17.6%), 215 (57.5%), and 93 (24.9%), respectively. l-Menthol efficacy was observed in 116 of the 127 treated lesions (91.3%), over 90% of which were in the posterior wall of the U region, anterior wall and greater curvature of the M region, and anterior wall and lesser curvature of the L region. The most and least effective areas for l-menthol application were the anterior wall of gastric antrum and posterior wall of the M region, respectively. The mean time from application to peristalsis inhibition was 8.7 s. No adverse effects were observed; perforation and secondary hemorrhage were not significantly different between the groups., Conclusion: Direct l-menthol application to the submucosal layer during mucosal resection affects smooth muscles and rapidly inhibits peristalsis resumption. Clinically, l-Menthol can be used to suppress peristalsis recurrence during ESD, without adverse effects., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Diagnosis using artificial intelligence (AI) with deep learning could be useful in endoscopic examinations. We investigated the ability of AI to detect superficial esophageal squamous cell carcinoma (ESCC) from esophagogastroduodenoscopy (EGD) videos. We retrospectively collected 8428 EGD images of esophageal cancer to develop a convolutional neural network through deep learning. We evaluated the detection accuracy of the AI diagnosing system compared with that of 18 endoscopists. We used 144 EGD videos for the two validation sets. First, we used 64 EGD observation videos of ESCCs using both white light imaging (WLI) and narrow-band imaging (NBI). We then evaluated the system using 80 EGD videos from 40 patients (20 with superficial ESCC and 20 with non-ESCC). In the first set, the AI system correctly diagnosed 100% ESCCs. In the second set, it correctly detected 85% (17/20) ESCCs. Of these, 75% (15/20) and 55% (11/22) were detected by WLI and NBI, respectively, and the positive predictive value was 36.7%. The endoscopists correctly detected 45% (25-70%) ESCCs. With AI real-time assistance, the sensitivities of the endoscopists were significantly improved without AI assistance (p < 0.05). AI can detect superficial ESCCs from EGD videos with high sensitivity and the sensitivity of the endoscopist was improved with AI real-time support.

In Japan, preoperatively diagnosed T1a-muscularis mucosae or T1b-submucosa 1 (MM/SM1) esophageal squamous cell carcinoma (ESCC) is a relative indication for endoscopic resection (ER). We evaluated long-term outcomes in patients after ER for non-circumferential ESCC with a preoperative diagnosis of MM/SM1 invasion. We retrospectively reviewed 66 patients with a preoperative diagnosis of non-circumferential MM/SM1 ESCC endoscopically resected between 2010 and 2015. Patients were divided into low- (adequate follow-up) and high-risk (requiring additional treatment) groups for lymph node metastasis according to risk factors (submucosal invasion, lymphovascular invasion, or droplet infiltration) and long-term outcomes were analyzed. Pathological invasion to T1a-lamina propria mucosa, MM/SM1, and T1b-SM2 was seen in 22, 38, and 6 lesions, respectively. Overall, 71.2% patients were classified into the "adequate follow-up" group. Of these, only one patient had a lymph node recurrence, which was successfully treated by additional therapy. The remaining 28.8% patients were classified into the "requiring additional treatment" group, where no recurrences were observed after additional treatments. After a median follow-up of 58.6 months, no deaths happened due to ESCC. The 3- and 5-year overall survival rates were 93.6% and 88.7%, respectively. ER is a valid initial treatment for non-circumferential ESCC with preoperatively diagnosed MM/SM1 invasion.

Background and Aims: Endoscopic submucosal dissection (ESD) has become an important and minimally invasive treatment for early gastric cancer (EGC) with a negligible risk of metastasis not only for differentiated-type (D-type) cancer but also for undifferentiated-type (UD-type) cancer. We aimed to investigate the incidence and characteristics of metachronous cancer after ESD for UD-type cancer, which has not yet been elucidated., Methods: In total, 175 patients who underwent ESD for UD-type EGC were enrolled. For comparison, 350 patients who underwent ESD for D-type EGC during the same period were randomly selected. These patients underwent a follow-up EGD annually. The median observation period was 6.0 years and 5.4 years, respectively., Results: The annual incidence of metachronous cancer after ESD for UD-type and D-type cancer was .9% and 5.3%, respectively. Among the patients who underwent ESD for UD-type cancer, 30.9% of patients were uninfected with Helicobacter pylori, whereas all patients who underwent ESD for D-type cancer were infected with H pylori. All patients who developed metachronous cancer were infected with H pylori. UD-type metachronous cancer developed more frequently in patients after ESD for UD-type cancer than after ESD for D-type cancer, and the curative resection rate of ESD was significantly lower in these cases., Conclusions: Metachronous cancers developed only in H pylori-infected patients in this cohort. Although metachronous cancer incidence was significantly less frequent in patients after ESD for UD-type cancer, the curative resection rate of ESD was significantly lower. Routine surveillance should be conducted more carefully after ESD for UD-type cancer, especially in H pylori-infected patients., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)