Evaluating the usefulness of considering the size and morphological type of type B2 vessel area based on Japan Esophageal Society classification in estimating tumor invasion depth in superficial esophageal squamous cell carcinomas: study protocol for a prospective observational study (Japan BEES study).

BACKGROUND: Accurate evaluation of tumor invasion depth is essential to determine the appropriate treatment strategy for patients with superficial esophageal cancer. The pretreatment tumor depth diagnosis currently relies on the magnifying endoscopic classification established by the Japan Esophageal Society (JES). However, the diagnostic accuracy of tumors involving the muscularis mucosa (MM) or those invading the upper third of the submucosal layer (SM1), which correspond to Type B2 vessels in the JES classification, remains insufficient. Previous retrospective studies have reported improved accuracy by considering additional findings, such as the size and macroscopic type of the Type B2 vessel area, in evaluating tumor invasion depth. Therefore, this study aimed to investigate whether incorporating the size and/or macroscopic type of the Type B2 vessel area improves the diagnostic accuracy of preoperative tumor invasion depth prediction based on the JES classification. METHODS: This multicenter prospective observational study will include patients diagnosed with MM/SM1 esophageal squamous cell carcinoma based on the Type B2 vessels of the JES classification. The tumor invasion depth will be evaluated using both the standard JES classification (standard-depth evaluation) and the JES classification with additional findings (hypothetical-depth evaluation) for the same set of patients. Data from both endoscopic depth evaluations will be electronically collected and stored in a cloud-based database before endoscopic resection or esophagectomy. This study's primary endpoint is accuracy, defined as the proportion of cases in which the preoperative depth diagnosis matched the histological depth diagnosis after resection. Outcomes of standard- and hypothetical-depth evaluation will be compared. DISCUSSION: Collecting reliable prospective data on the JES classification, explicitly concerning the B2 vessel category, has the potential to provide valuable insights. Incorporating additional findings into the in-depth evaluation process may guide clinical decision-making and promote evidence-based medicine practices in managing superficial esophageal cancer. TRIAL REGISTRATION: This trial was registered in the Clinical Trials Registry of the University Hospital Medical Information Network (UMIN-CTR) under the identifier UMIN000051145, registered on 23/5/2023.

Is proton-pump inhibitor effective in preventing postoperative bleeding after esophageal endoscopic submucosal dissection?

Although proton-pump inhibitor (PPI) administration was reported to be effective in preventing delayed bleeding after gastric endoscopic submucosal dissection (ESD), its effectiveness in esophageal ESD is still unknown. We assessed whether PPI or vonoprazan administration was effective in preventing posterior hemorrhage after esophageal ESD. This retrospective cohort study used the Japanese Diagnosis Procedure Combination (DPC) database, and patients who underwent esophageal ESD between January 2012 and December 2020 were enrolled. The participants were divided into two groups: patients who were prescribed PPI or vonoprazan (PPI or vonoprazan group) and those who were not prescribed PPI (no acid suppression). Propensity score matching analysis was performed, and the delayed bleeding rate was compared between the groups. We analyzed 54,345 patients, of whom 8237 (15.16%) were in the no acid suppression group and 46,108 (84.84%) in the PPI or vonoprazan group (PPI: 34,380 and vonoprazan: 11,728). Delayed bleeding occurred in 1126 patients (2.07%). A total of 8237 pairs were created after matching. Delayed bleeding was not significantly different between the no acid suppression group and PPI or vonoprazan group, respectively (odds ratio: 1.20, 95% confidential interval: 0.93-1.54, P = 0.227). A sub-analysis according to the dose of PPI or vonoprazan, tumor location, and prescription of antithrombotic or anticoagulant medications was performed, but no significant effects of PPI or vonoprazan administration were found. PPI or vonoprazan did not prevent delayed bleeding; thus, the prescription of PPI and vonoprazan after esophageal ESD may not be recommended for the prevention of delayed bleeding.

A simpler diagnostic algorithm of the Japan Esophageal Society classification for Barrett's esophagus-related superficial neoplasia.

BACKGROUND: We previously developed a Japan Esophageal Society Barrett's Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN. METHODS: We used data from our previous study, including 10 reviewers' assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN. RESULTS: Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers' assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%). CONCLUSION: The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

Usefulness of the S-O clip for duodenal endoscopic submucosal dissection: a propensity score-matched study.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) for superficial non-ampullary duodenal tumors (SNADETs) is associated with a high rate of en bloc resection. However, the technique for ESD remains challenging. Recent studies have demonstrated the effectiveness of S-O clips in colonic and gastric ESD. We evaluated the efficacy and safety of duodenal ESD using an S-O clip for SNADETs. METHODS: Consecutive patients who underwent ESD for SNADETs between January 2011 and December 2021 were retrospectively enrolled. Propensity score matching analysis was used to compare patients who underwent duodenal ESD with the S-O clip (S-O group) and those who underwent conventional ESD (control group). Intraoperative perforation rate was the primary outcome, while procedure time and R0 resection rate were the secondary outcomes. RESULTS: After propensity score matching, 16 pairs were created: 43 and 17 in the S-O and control groups, respectively. The intraoperative perforation rate in the S-O group was significantly lower than that in the control group (p=0.033). A significant difference was observed in the procedure time between the S-O and control groups (39±9 vs. 82±30 minutes, respectively; p=0.003). CONCLUSION: The S-O clip reduced the intraoperative perforation rate and procedure time, which may be useful and effective in duodenal ESD.

Curative Management After Endoscopic Resection for Esophageal Squamous Cell Carcinoma Invading Muscularis Mucosa or Shallow Submucosal Layer-Multicenter Real-World Survey in Japan.

INTRODUCTION: Curative management after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), which invades the muscularis mucosa (pMM-ESCC) or shallow submucosal layer (pSM1-ESCC), has been controversial. METHODS: We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data were based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER. RESULTS: A total of 992 patients with pMM-ESCC (n = 749) and pSM1-ESCC (n = 243) were registered. According to the multivariate Cox proportional hazards analysis, pSM1-ESCC (hazard ratio = 1.88, 95% confidence interval 1.15-3.07, P = 0.012) and LVI (hazard ratio = 6.92, 95% confidence interval 4.09-11.7, P < 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1-233), among patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients with additional treatment were significantly better than those of patients without additional treatment; 85.4% vs 61.5% ( P < 0.0001), 80.5% vs 53.3% ( P < 0.0001), and 98.5% vs 93.1% ( P = 0.004), respectively. There was no difference in survival rate between the chemoradiotherapy and surgery groups. DISCUSSION: pSM1 and LVI were risk factors for metastasis after ER for ESCC. To improve the survival, additional treatment immediately after ER, such as chemoradiotherapy or surgery, is effective in patients with these risk factors.

Impact of COVID-19 on the endoscopy department since the early phase of the pandemic in 2020: A questionnaire study among patients with canceled examinations at a single Japanese institution.

INTRODUCTION: In early 2020, the Japanese government declared a nationwide state of emergency for the COVID-19 pandemic. We investigated the impact of the emergency declaration on endoscopy adherence and conducted a follow-up study of patients with canceled examinations at a tertiary endoscopy facility in Japan in 2020. METHODS: We compared the number of endoscopies performed, and cancelations at the endoscopy unit between 2019 and 2020 and used the Bayesian structural time series (BSTS) model to estimate the decrease in the number of endoscopies in 2020. We administered a questionnaire to those who had not undergone a scheduled endoscopy. RESULTS: Of 14 146 and 13 338 scheduled examinations, 1233 (8.7%) and 1403 (10.5%) were canceled in 2019 and 2020, respectively. During both years, age < 50 years, age > 80 years, upper endoscopy, and experience of endoscopy in the past 5 years were significantly associated with cancelations. In 2020, cancelations in the 14th-26th week of the year, including the period of state of emergency, increased significantly, and more women canceled. Of the 409 questionnaire-respondents, 174 (42.5%) indicated that COVID-19 had influenced their cancelation, and 315 (77.0%) had not undergone similar endoscopic examinations since then. The BSTS model predicted a decrease of 957 (95% CI -1213 to -708, P = .003) examinations. CONCLUSION: In 2020, despite low numbers of COVID-19 cases in the study site, the number of endoscopies decreased, and cancelation increased. Further research is needed on the future impact of a decrease in the number of endoscopies during a COVID-19 pandemic.

Colitis with Hypereosinophilia following the Second Dose of the BNT162b2 mRNA COVID-19 Vaccine: A Case Report with a Literature Review.

A 61-year-old man presented with a 7-day history of watery diarrhea and loss of appetite after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. Laboratory studies showed significant eosinophilia and an elevated IgE level (white cell count, 18.4×109/L; eosinophil count, 9.5×109/L; and IgE level, 540 IU/L). Symptoms resolved 10 days after vaccination without any steroids or antiallergic medications, and the eosinophil count had also returned to within normal limits 2 months later. Several cases of eosinophilic disorders following receipt of any type of injectable COVID-19 vaccine have been reported, so the etiology should be examined.

Prognostic Benefit of Additional Treatment After Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Although additional treatment is considered for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic submucosal dissection (ESD), the actual benefits of this method remain to be elucidated. AIMS: We aimed to evaluate the prognostic benefits of additional treatment in such patients. METHODS: Between 2006 and 2017, we enrolled patients with pT1a-MM/pT1b-SM ESCC after ESD at 21 institutions in Japan. Overall survival (OS) and disease-specific survival (DSS) were compared between the additional treatment and follow-up groups after propensity score matching, to reduce the bias of baseline characteristics. A subgroup analysis was performed according to the pathological findings: category A, pT1a-MM but negative for lymphovascular invasion (LVI) and vertical margin (VM); category B, tumor invasion into the submucosa ≤ 200 µm but negative for LVI and VM; category C, others. RESULTS: Of 593 patients with pT1a-MM/pT1b-SM ESCC after ESD, 101 matched pairs were extracted after propensity score matching. The OSs were similar between the additional treatment and follow-up groups (80.6% vs. 78.6% in 5 years; P = 0.972). In a subgroup analysis, the OS in the additional treatment group was significantly lower than that in the follow-up group (65.7% vs. 95.2% in 5 years; P = 0.037) in category A, whereas OS did not significantly differ in category C (76.8% vs. 69.5% in 5 years; P = 0.360). CONCLUSIONS: Additional treatment after ESD in patients with pT1a-MM/pT1b-SM ESCC was not associated with an improved prognosis.

Muscular metastasis of superficial esophageal squamous cell carcinoma: a rare case of recurrence after endoscopic submucosal dissection with additional chemoradiotherapy.

Esophageal cancer after endoscopic treatment may recur depending on the risk. We present a case of a rare T1b esophageal cancer after endoscopic treatment plus chemoradiotherapy (CRT) that recurred with metastasis of the dorsal muscles. A 70-year-old man was referred for treatment of early-stage esophageal carcinoma. Endoscopic submucosal dissection (ESD) was performed and histopathology showed a poorly differentiated squamous cell carcinoma with invasion to the submucosal layer (sm2) with INFc-type invasion and positive venous invasion. After subsequent CRT, the patient was monitored every 6 months, using computed tomography (CT) and endoscopy. Fifteen months after the treatment, contrast CT revealed a spherical mass with 9 cm ring enhancement within the right erector spinae, that had squamous cell carcinoma confirmed by CT-guided biopsy. Radiation and systemic chemotherapy were initiated for the metastasis of the esophageal carcinoma. However, he died of respiratory failure due to rapid pleural effusion 26 months after ESD. Pathological autopsy showed diffuse squamous cell carcinoma invasion of the cystic wall, forming a lumbar mass, and absence of cancer cell remnants or recurrences in the esophagus. This case report emphasizes the need for systemic observation of superficial esophageal cancer after treatment with a high risk of recurrence.

Assigning a different endoscopist for each annual follow-up may contribute to improved gastric cancer detection rates.

Background and study aims Esophagogastroduodenoscopy (EGD) is an effective and important diagnostic tool to detect gastric cancer (GC). Although previous studies show that examiner, patient, and instrumental factors influence the detection of GC, we analyzed whether assigning a different examiner to surveillance EGD would improve the detection of GC compared to assigning the same examiner as in the previous endoscopy. Patients and methods We retrospectively reviewed patients who underwent two or more consecutive surveillance EGDs at a single center between 2017 and 2019. We identified factors associated with GC detection using multivariable regression analysis and propensity-score matching. Results Among 7794 patients, 99 GC lesions in 93 patients were detected by surveillance EGD (detection rate; 1.2 %), with a mean surveillance interval of 11.2 months. Among the detected 99 lesions, 87 (87.9 %) were curatively treated with endoscopy. There were no differences in the clinicopathologic characteristics of GC detected by the same or different endoscopists. GC detection in the group examined by different endoscopists was more statistically significant than in the group examined by the same endoscopist, even after propensity-score matching (1.6 % and 0.7 %; P  < 0.05). Endoscopic experience and other factors were not statistically significant between the two groups. Conclusions In surveillance EGD, having a different endoscopist for each exam may improve GC detection rates, regardless of the endoscopist's experience.

Which factors make Barrett's esophagus lesions difficult to diagnose?

Background and study aims Although the Japan Esophageal Society's magnifying endoscopic classification for Barrett's epithelium (JES-BE) offers high diagnostic accuracy, some cases are challenging to diagnose as dysplastic or non-dysplastic in daily clinical practice. Therefore, we investigated the diagnostic accuracy of this classification and the clinicopathological features of Barrett's esophagus cases that are difficult to diagnose correctly. Patients and methods Five endoscopists with experience with fewer than 10 cases of magnifying observation for superficial Barrett's esophageal carcinoma reviewed 132 images of Barrett's mucosa or carcinoma (75 dysplastic and 57 non-dysplastic cases) obtained using high-definition magnification endoscopy with narrow-band imaging (ME-NBI). They diagnosed each image as dysplastic or non-dysplastic according to the JES-BE classification, and the diagnostic accuracy was calculated. To identify risk factors for misdiagnosed images, images with a correct rate of less than 40 % were defined as difficult-to-diagnose, and those with 60 % or more were defined as easy-to-diagnose. Logistic regression analysis was performed to identify risk factors for difficult-to-diagnose images. Results The sensitivity, specificity and overall accuracy were 67 %, 80 % and 73 %, respectively. Of the 132 ME-NBI images, 34 (26 %) were difficult-to-diagnose and 99 (74 %) were easy-to-diagnose. Logistic regression analysis showed low-grade dysplasia (LGD) and high-power magnification images were each significant risk factors for difficult-to-diagnose images (OR: 6.80, P  = 0.0017 and OR: 3.31, P  = 0.0125, respectively). Conclusions This image assessment study suggested feasibility of the JES-BE classification for diagnosis of Barrett's esophagus by non-expert endoscopists and risk factors for difficult diagnosis as high-power magnification and LGD histology. For non-experts, high-power magnification images are better evaluated in combination with low-power magnification images.

Impact of upgraded radiotherapy system on outcomes in postoperative head and neck squamous cell carcinoma patients.

Background: This study was performed to evaluate the impact of upgrade of radiotherapy system, including launch of intensity-modulated radiation therapy (IMRT), on the therapeutic outcomes. Materials and methods: Patients with head and neck (H&N) squamous cell carcinoma (SCC) who underwent postoperative radiotherapy at our hospital between June 2009 and July 2019 were retrospectively reviewed. In July 2014, we converted the radiotherapy technique for these patients from a 3-dimensional conformal radiotherapy (3D-CRT) to IMRT, along with the adoption of a meticulous planning policy and a few advanced procedures, including online imaging guidance. Results: A total of 136 patients (57 treated with the previous system and 79 treated with the upgraded system) were reviewed. There were significantly more patients with extracapsular extension in the upgraded-system group than the previous-system group (p = 0.0021). There were significantly fewer patients with ≥ Grade 2 acute and late adverse events in the upgraded-system group than the previous-system group. The differences in progression-free survival (PFS), distant metastasis-free survival (DFFS), locoregional progression-free survival (LRPFS), and overall survival (OS) between the two groups were not statistically significant (p = 0.8962, 0.9926, 0.6244, and 0.4827, respectively). Multivariate analysis revealed that the upgrade had neither positive nor negative impact on survival outcomes. Extracapsular extension was independently associated with decreased LRPFS and OS (p = 0.0499 and 0.0392, respectively). Conclusions: The IMRT-centered upgrade was beneficial for the postoperative patients with H&N SCC, because survival outcomes were sustained with less toxicities.

Automatic anatomical classification of colonoscopic images using deep convolutional neural networks.

BACKGROUND: A colonoscopy can detect colorectal diseases, including cancers, polyps, and inflammatory bowel diseases. A computer-aided diagnosis (CAD) system using deep convolutional neural networks (CNNs) that can recognize anatomical locations during a colonoscopy could efficiently assist practitioners. We aimed to construct a CAD system using a CNN to distinguish colorectal images from parts of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. METHOD: We constructed a CNN by training of 9,995 colonoscopy images and tested its performance by 5,121 independent colonoscopy images that were categorized according to seven anatomical locations: the terminal ileum, the cecum, ascending colon to transverse colon, descending colon to sigmoid colon, the rectum, the anus, and indistinguishable parts. We examined images taken during total colonoscopy performed between January 2017 and November 2017 at a single center. We evaluated the concordance between the diagnosis by endoscopists and those by the CNN. The main outcomes of the study were the sensitivity and specificity of the CNN for the anatomical categorization of colonoscopy images. RESULTS: The constructed CNN recognized anatomical locations of colonoscopy images with the following areas under the curves: 0.979 for the terminal ileum; 0.940 for the cecum; 0.875 for ascending colon to transverse colon; 0.846 for descending colon to sigmoid colon; 0.835 for the rectum; and 0.992 for the anus. During the test process, the CNN system correctly recognized 66.6% of images. CONCLUSION: We constructed the new CNN system with clinically relevant performance for recognizing anatomical locations of colonoscopy images, which is the first step in constructing a CAD system that will support us during colonoscopy and provide an assurance of the quality of the colonoscopy procedure.

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett's esophagus-related neoplasms: a nationwide multicenter study.

BACKGROUND: Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett's esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society-Barrett's esophagus working group (JES-BE) for superficial Barrett's esophagus-related neoplasms. METHODS: The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. RESULTS: The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. CONCLUSION: The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician's experience level.

Risk of metastatic recurrence after endoscopic resection for esophageal squamous cell carcinoma invading into the muscularis mucosa or submucosa: a multicenter retrospective study.

BACKGROUND: We aimed to elucidate the risk of metastatic recurrence after endoscopic resection (ER) without additional treatment for esophageal squamous cell carcinomas (ESCCs) with tumor invasion into the muscularis mucosa (pT1a-MM) or submucosa (T1b-SM). METHODS: We retrospectively enrolled patients with pT1a-MM/pT1b-SM ESCC after ER at 21 institutions in Japan between 2006 and 2017. We compared metastatic recurrence between patients with and without additional treatment, stratified into category A (pT1a-MM with negative lymphovascular invasion [LVI] and vertical margin [VM]), B (tumor invasion into the submucosa ≤ 200 µm [pT1b-SM1] with negative LVI and VM), and C (others). Subsequently, using multivariate Cox analysis, we evaluated risk factors for metastatic recurrence after ER without additional treatment. RESULTS: We enrolled 593 patients, and metastatic recurrence occurred in 38 patients. Metastatic recurrence after additional treatment was significantly lower than that after no additional treatment in category C (9.1% vs. 23.6% in 5 years, p = 0.001), whereas no significant difference was noted in categories A (0.0% vs. 2.6%) and B (0.0% vs. 4.3%). In patients without additional treatment after ER, risk factors for metastatic recurrence were lymphatic invasion (hazard ratio [HR], 5.61), positive VM (HR, 4.55), and tumor invasion into the submucosa > 200 µm (HR, 3.25), and, but near half of the patients with metastatic recurrence had no further recurrence after salvage treatment, resulting in excellent 5-year disease-specific survival in categories A (99.6%) and B (100.0%). CONCLUSIONS: Closed follow-up with no additional treatment may be an acceptable option after ER in pT1a-MM/pT1b-SM1 ESCC with negative LVI and VM.