Esophageal Lesions Research Articles

741. EXPRESSION OF COX2 AND P53 IN RAT ESOPHAGEAL CANCER INDUCED BY REFLUX OF DUODENAL CONTENTS

Abstract Aim. Reflux of duodenal contents can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and p53 in rat esophageal lesions induced by duodenal content reflux. Methods. Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. Ten rats were the sham. Control. They were sacrificed at the 40th week. Their esophagi were examined for HE, COX2, p53, and proliferating cell nuclear antigen (PCNA). Results. After 40 weeks of reflux, dysplasia, squamous cell carcinoma (SCC), and adenocarcinoma (ADC) were found. PCNA labeling index was higher in dysplastic and cancer tissue than that in normal. Overexpression of COX2 was shown in ADC and SCC. Wild-type p53 accumulation was found in ADC, and not in SCC. Conclusion. Reflux of duodenal contents into the esophagus led to ADC and SCC in rats. COX2 may play an important role in esophageal cancer by duodenal content reflux. Our present results suggest an association between wild-type p53 accumulation and COX2 expression in ADC, with no such relation seen in SCC.

Ligation-assisted endoscopic submucosal resection following unroofing technique for small esophageal subepithelial lesions originating from the muscularis propria.

The majority of esophageal subepithelial lesions originating from the muscularis propria (SEL-MPs) are benign in nature, although a subset may exhibit malignant characteristics. Conventional endoscopic resection techniques are time-consuming and lack efficacy for small SEL-MPs. To evaluate the efficacy and safety of ligation-assisted endoscopic submucosal resection (ESMR-L) following unroofing technique for small esophageal SEL-MPs. From January 2021 to September 2023, 17 patients diagnosed with esophageal SEL-MPs underwent ESMR-L following unroofing technique at the endoscopy center of Shenzhen People's Hospital. Details of clinicopathological characteristics and clinical outcomes were collected and analyzed. The mean age of the patients was 50.12 ± 12.65 years. The mean size of the tumors was 7.47 ± 2.83 mm and all cases achieved en bloc resection successfully. The average operation time was 12.2 minutes without any complications. Histopathology identified 2 Lesions (11.8%) as gastrointestinal stromal tumors at very low risk, 12 Lesions (70.6%) as leiomyoma and 3 Lesions (17.6%) as smooth muscle proliferation. No recurrence was found during the mean follow-up duration of 14.18 ± 9.62 months. ESMR-L following roofing technique is an effective and safe technique for management of esophageal SEL-MPs smaller than 20 mm, but it cannot ensure en bloc resection and may require further treatment.

Novel ultrasound capsule endoscopy for gastrointestinal scanning: An in vivo animal study.

EUS is an important modality for diagnosis and assessment of gastrointestinal (GI) subepithelial lesions. However, EUS is invasive and operator-dependent and requires sedation in most cases. The newly developed ultrasound capsule endoscopy (USCE) system, with both white-light and ultrasound imaging modalities, is a minimally invasive method for superficial and submucosal imaging of the esophagus. This animal study aimed to evaluate the feasibility and efficacy of the USCE system for upper GI tract and small bowel scanning. Three Bama miniature pigs were selected to scan their esophagus, stomach, small bowel, and simulated submucosal lesions. USCE was performed first, followed by EUS. The feasibility of USCE was measured by obtaining ultrasound images of normal GI walls and submucosal lesions under the guidance of optical viewing. The efficacy of USCE was evaluated by comparing tissue structures and lesion features shown on ultrasound images obtained with both instruments. Under the optical mode of USCE, the GI tract was well visualized, and all simulated lesions were located. Clear ultrasound images of normal GI tract and submucosal lesions were acquired. Ultrasound images of the esophagus, stomach, and small bowel were characterized by differentiated multilayer structures on USCE, which was consistent with the structures displayed on EUS. And the visualization of submucosal lesions, using both USCE and EUS, was characterized by a hypoechoic and well-demarcated mass in the layer of submucosa. This animal study indicated the feasibility and potential clinical efficacy of this USCE for simultaneous optical mucosal visualization and transmural ultrasound imaging of upper GI tract and small bowel, providing possibility of using this technology for a wider range of GI tract.

Management of subepithelial esophageal tumors

Abstract Subepithelial esophageal tumors (SET) are normally benign intramural esophageal lesions of mesenchymal origin. Although rare, the incidence of SET has increased in recent decades due to the more widespread use of endoscopy and diagnostic imaging. The current review aims to provide an overview of the histopathologic spectrum and the most frequent entities including leiomyoma and gastrointestinal stromal tumor (GIST), diagnostic workup, and multidisciplinary treatment options. Staging for SET should include endoscopy, endoscopic ultrasonography (EUS), and tissue sampling. Current consensus guidelines recommend that SET suggestive of gastrointestinal stromal tumor (GIST) larger than 20 mm or lesions with high-risk stigmata should undergo tissue sampling. Most SET have an excellent long-term outcome, but malignancy may be present in certain subtypes. Asymptomatic SET without high-risk stigmata discovered incidentally usually do not require specific treatment. However, depending on the size and location of the lesion symptoms may occur. Therapeutic interventions range from endoscopic interventional resections to major surgical procedures. Enucleation via minimally invasive or robotic-assisted access remains the standard of care for most SET sub-entities.

Ex vivo optical coherence tomography combined with near infrared targeted fluorescence: towards in-vivo esophageal cancer detection.

Early detection of (pre)malignant esophageal lesions is critical to improve esophageal cancer morbidity and mortality rates. In patients with advanced esophageal adenocarcinoma (EAC) who undergo neoadjuvant chemoradiation therapy, the efficacy of therapy could be optimized and unnecessary surgery prevented by the reliable assessment of residual tumors after therapy. Optical coherence tomography (OCT) provides structural images at a (sub)-cellular level and has the potential to visualize morphological changes in tissue. However, OCT lacks molecular imaging contrast, a feature that enables the study of biological processes at a cellular level and can enhance esophageal cancer diagnostic accuracy. We combined OCT with near-infrared fluorescence molecular imaging using fluorescently labelled antibodies (immuno-OCT). The main goal of this proof of principle study is to investigate the feasibility of immuno-OCT for esophageal cancer imaging. We aim to assess whether the sensitivity of our immuno-OCT device is sufficient to detect the tracer uptake using an imaging dose (∼100 times smaller than a dose with therapeutic effects) of a targeted fluorescent agent. The feasibility of immuno-OCT was demonstrated ex-vivo on dysplastic lesions resected from Barrett's patients and on esophageal specimens resected from patients with advanced EAC, who were respectively topically and intravenously administrated with the tracer bevacizumab-800CW. The detection sensitivity of our system (0.3 nM) is sufficient to detect increased tracer uptake with micrometer resolution using an imaging dose of labelled antibodies. Moreover, the absence of layered structures that are typical of normal esophageal tissue observed in OCT images of dysplastic/malignant esophageal lesions may further aid their detection. Based on our preliminary results, immuno-OCT could improve the detection of dysplastic esophageal lesions.

A pilot study on endoscopic delivery of injectable bioadhesive for esophageal repair in a porcine model

Endoscopic submucosal dissection (ESD) is the gold-standard surgical procedure for superficial esophageal cancer. A significant and challenging complication of this technique is post-ESD esophageal stricture. In this study, the feasibility of endoscopic catheter delivery of bioadhesive to esophageal lesions in a porcine model was tested. Injectable bioadhesive was composed of oxidized dextran (ODA) and chitosan hydrochloride (CS), its physicochemical properties, injectability, antibacterial activity, and cytocompatibility were investigated beforein vivotest. ODA-CS bioadhesive was delivered to the wound bed of the esophageal tissue using a custom-made catheter device after ESD in a porcine model. Our results show that the ODA-CS bioadhesive is of good injectability, tissue adhesive strength, antibacterial capacity, and blood compatibility.In vivodelivery was achieved by endoscopic spraying of ODA and CS in separate catheters fixed on the endoscopic probe. ODA and CS can be mixed well to allow in situ bioadhesive formation and firmly adhere to the esophageal wound surface. After two weeks, the bioadhesive maintained structural integrity and adhered to the surface of esophageal wounds. However, histological analysis reveals that the ODA-CS bioadhesive did not show improvement in attenuating inflammatory response after ESD. This pilot study demonstrates the feasibility of ODA-CS bioadhesive for shielding esophageal wounds after ESD, whereas efforts need to improve its anti-inflammatory activity to reduce fibrosis for stricture prevention.

A novel strategy for performing endoscopic submucosal dissection for circumferential superficial esophageal neoplastic lesions with kissing traction.

A novel strategy for performing endoscopic submucosal dissection for circumferential superficial esophageal neoplastic lesions with kissing traction.

Ameliorative Effects of HT074-Inula and Paeonia Extract Mixture on Acute Reflux Esophagitis in Rats via Antioxidative Activity.

HT074, a multiherbal mixture containing extracts from Inula britannica flowers and Paeonia lactiflora roots, is used in Korean medicine for gastric disorders. This study investigated the protective mechanisms of HT074 against acute reflux esophagitis (RE) in rats. Nitric oxide (NO) production and mRNA expression of antioxidant-related genes (Nrf2, HO-1, SOD, CAT, and GPx2) were evaluated in LPS-induced RAW 264.7 cells. Gastroesophageal reflux (GER) was induced in rats, followed by HT074 (100, 300 mg/kg) or ranitidine (50 mg/kg) administration. Esophageal damage and histological changes were assessed. Gastric pH and protein expression levels of Nrf2, HO-1, SOD, CAT, and GPx-1/2 were measured. HT074 pretreatment reduced NO production and increased the expression of HO-1, CAT, and GPx2 in LPS-induced RAW 264.7 cells. In GER-induced rats, HT074 significantly decreased esophageal lesions and increased the expression of HO-1, SOD, GPx-1/2, and Nrf2. HT074 did not affect gastric pH. These findings suggest that HT074 protects against GER-induced esophagitis by inhibiting NO production and enhancing antioxidant activity. Therefore, HT074 could be a promising therapeutic agent for GER disease.

Efficacy and safety of pulsed-field versus conventional thermal ablation for atrial fibrillation: A systematic review and meta-analysis.

Pulsed-field ablation (PFA) has emerged as an innovative alternative to radiofrequency (RF) and cryoablation because it selectively targets myocardial tissue. Thus, we aim to estimate the efficacy and safety of PFA versus thermal ablation for atrial fibrillation (AF) ablation. A systematic review and meta-analysis were retrieved from PubMed, WOS, SCOPUS, EMBASE, and CENTRAL through September 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42023480321. We included 17 studies with a total of 2255 patients. PFA was significantly associated with a decreased incidence of AF recurrence (RR: 0.66 with 95% CI [0.51, 0.87], p = .003). However, there was no significant difference between PFA and thermal ablation in arrhythmia recurrence (RR: 0.92 with 95% CI [0.74, 1.46], p = .42). PFA was significantly associated with decreased total procedure time (MD: -15.15 with 95% CI [-20.23, -10.07], p < .00001), decreased heart rate change (MD: -7.39 with 95% CI [-12.16, -2.62], p = .002), decreased phrenic nerve palsy (RR: 0.38 with 95% CI [0.15, 0.98], p = .05), and reduced esophageal lesions (RR: 0.09 with 95% CI [0.01, 0.69], p = .02). On the contrary, PFA was significantly associated with increased pericardial tamponade (RR: 6.14 with 95% CI [1.43, 26.33], p = .01). PFA was significantly associated with decreased AF recurrence, total procedure time, heart rate change, phrenic nerve palsy, esophageal lesion, and increased incidence of pericardial tamponade compared with thermal ablation.

Per oral endoscopic myotomy in esophageal achalasia in children. First endoscopic procedures

BACKGROUND: Achalasia is an esophagus lesion which is characterized by disorders of its motility. It is met extremely rare in childhood. Among the existing techniques of achalasia management, Heller's laparoscopic myotomy is a procedure of choice. Peroral endoscopic myotomy (POEM) is an endoscopic method for AP treating proposed by P. Pasricha in 2007. AIM: To describe the experience of per oral endoscopic myotomy in children. METHODS: The authors performed a retrospective analysis of data taken from the patients with confirmed esophageal achalasia who had had POEM. Clinical efficacy was assessed using the Eckard scale. RESULTS: In 2018–2021, 8 children with average age 14.4 years were treated with POEM surgery. Before POEM, 2 children underwent balloon dilatation of the cardia. The surgery was technically performed in all children. Dysphagia was eliminated in all patients, and none of them required any additional intervention. A significant decrease in Eckard scale scores was registered in all children after surgery. CONCLUSION: Our results confirm findings that POEM is an effective procedure for treating esophageal achalasia. However, a longer follow-up period and a larger group of patients are needed to confirm POEM role in the management of children with esophageal achalasia.

Combining non-invasive liquid biopsy and a methylation analysis to assess surgical risk for early esophageal cancer.

While the widespread use of endoscopic submucosal dissection (ESD) has significantly reduced the incidence of early esophageal cancer (ESCA), the limited ability of ESD to strip deep infiltrating esophageal lesions results in a considerable risk of intraoperative perforation. Circulating-free DNA (cfDNA) is widely used in modern tumor screening due to its non-invasive detection capabilities. A methylation analysis offers vital insights into the condition and advancement of malignancies due to its unique positioning, such as a marker of cancer. This study investigated the potential of combining a non-invasive liquid biopsy technique, along with a methylation analysis, to assess the surgical perforation risk of ESCA patients. In this study, we conducted an analysis of gene expression differences between stage I esophageal squamous carcinoma samples and healthy tissue samples using data from The Cancer Genome Atlas (TCGA) database. We also identified the genes associated with progression-free survival (PFS) in esophageal squamous carcinoma. Integrating the framework of the methylation analysis, we explored the methylated sites of these distinct genes. To refine this process, we used the Shiny Methylation Analysis Resource Tool (SMART) to conduct a comprehensive analysis of these sites. We then confirmed the stability of the methylation sites in different lesion conditions using methylation-specific quantitative polymerase chain reaction (MS-qPCR) with paraffin tissue samples collected after ESD. We analyzed RNA-sequencing data from 42 early stage ESCA patients and 17 controls, identifying 1,263 up-regulated and 460 down-regulated genes. Functional analyses revealed involvement in key pathways such as cell cycle regulation and immune responses. Furthermore, we identified 38 differentially expressed genes associated with PFS. Using SMART analysis, we found 217 hyper-methylated regions in 38 genes, suggesting potential early markers for ESCA. Validation experiments confirmed the reliability of 29 hyper-methylated regions in FFPE tissue samples and 6 regions in cfDNA. A LunaCAM model showed high accuracy [area under the curve (AUC) =0.89] in discriminating early ESCA. Integrated assessment of six highly methylated regions significantly improved predictive performance, with 90.56% sensitivity, highlighting the importance of combinatorial biomarker evaluation for early cancer detection. This study established a novel approach that integrates non-invasive testing with a methylation analysis to assess the surgical risk of early ESCA patients. The significance of changes in methylation sites in relation to lesion status should not be underestimated, as they have the potential to offer vital insights for proactive risk assessments before surgery.

Cryoballoon-Assisted Pulmonary Vein Isolation and Left Atrial Roof Ablation Using a Simplified Sedation Strategy without Esophageal Temperature Monitoring: No Notable Thermal Esophageal Lesions and Low Arrhythmia Recurrence Rates after 2 Years.

Atrial fibrillation (AF) ablation is increasingly effective for managing heart rhythm but poses risks like esophageal fistulas. Minimizing esophageal thermal lesions while simplifying procedures is crucial. This prospective study involved 100 consecutive AF patients undergoing cryoballoon ablation with simplified sedation, without esophageal temperature monitoring. Patients with paroxysmal AF (Group A) received pulmonary vein isolation only, while those with persistent AF (Group B) also had left atrial roof ablation. Gastroesophageal endoscopy was performed post-procedure to detect lesions, and cardiological follow-ups were conducted at 3, 12, and 24 months. The cohort included 69% men, with a median age of 65.5 years. Post-ablation endoscopy was performed in 92 patients; esophageal lesions were found in 1.1% of Group A and none of Group B. GERD was diagnosed in 14% of patients, evenly distributed between groups and not linked to lesion occurrence. Gastric hypomotility was observed in 16% of patients, with no significant difference between groups. At 24 months, arrhythmia-free survival was 88% in Group A and 74% in Group B. Cryoballoon-assisted pulmonary vein isolation, with or without additional left atrial roof ablation and without esophageal temperature monitoring during a simplified sedation strategy, shows low risk of esophageal thermal injury and effective ablation outcomes.

Discovery and validation of combined biomarkers for the diagnosis of esophageal intraepithelial neoplasia and esophageal squamous cell carcinoma

Early diagnosis and intervention of esophageal squamous cell carcinoma (ESCC) can improve the prognosis. The purpose of this study was to identify biomarkers for ESCC and esophageal precancerous lesions (intraepithelial neoplasia, IEN). Based on the proteomic and genomic data of esophageal tissue including previously reported data, up-regulated proteins with copy number amplification in esophageal cancer were screened as candidate biomarkers. Five proteins, including KDM2A, RAD9A, ECT2, CYHR1 and TONSL, were confirmed by immunohistochemistry on ESCC and normal esophagus (NE). Then, we investigated the expression of 5 proteins in 236 participants (60 NEs, 93 IENs and 83 ESCCs) which were randomly divided into training set and test set. When distinguishing ESCC from NE, the area under curve (AUC) of the multiprotein model was 0.940 in the training set, while the lowest AUC of a protein was 0.735. In the test set, the results were similar. When distinguishing ESCC from IEN or distinguishing IEN from NE, the diagnostic efficiency of the multi-protein models were also improved compared with that of single protein. Our findings suggest that combined detection of KDM2A, RAD9A, ECT2, CYHR1 and TONSL can be used as potential biomarkers for the early diagnosis of ESCC and precancerous lesion development prediction. SignificanceCandidate biomarkers including KDM2A, RAD9A, ECT2, CYHR1 and TONSL screened by integrating genomic and proteomic data from the esophagus can be used as potential biomarkers for the early diagnosis of esophageal squamous cell carcinoma and precancerous lesion development prediction.

Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA

Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.

Combined Endovascular and Endoscopic Management of a Secondary Aortoesophageal Fistula after Open Surgical Aortic Repair in a Giant Descending Thoracic Aortic Pseudoaneurysm: Case Report and Review of Literature.

Secondary aortoesophageal fistula (AEF) is defined as a communication between the aorta and the esophagus, occurring after aortic disease treatment or esophageal procedures, associating very high mortality rates with treatment and being fatal without it. Several treatment strategies have been described in the literature, combining open surgery or endovascular aortic repair with surgical or endoscopic management of the esophageal lesion. We present the case of a 53-year-old patient with a history of open aortic surgery for a giant descending thoracic aortic pseudoaneurysm complicated with secondary AEF, successfully managed using emergency transiliac TEVAR (thoracic endovascular aortic repair), extensive antibiotic therapy associated with nutritional replenishment, and rehabilitation therapy. Novel endovascular and endoscopic devices have been developed, offering less invasive treatment strategies with improved outcomes, especially for high risk surgical patients. This case highlights the importance of a multidisciplinary approach to personalized medicine to manage such complex situations.

Synchronous cancers of the stomach and esophagus in a patient with autoimmune gastritis and pernicious anemia: a case report and review of the literature.

Type-A gastritis/autoimmune gastritis (AIG) has gained renewed attention due to declining Helicobacter pylori infection rates and increasing eradication. AIG is associated with pernicious anemia (PA) and is prone to complicate various tumors, such as gastric cancer and neuroendocrine tumors. This report describes a case of AIG with PA in which gastric and esophageal cancers arose simultaneously. An 86-year-old woman had been diagnosed with PA and AIG 9 years earlier. As routine blood tests revealed high levels of carcinoembryonic antigen, she underwent esophagogastroduodenoscopy, which revealed a type 0-IIa lesion in the middle part of the stomach and a type 0-IIa + IIb lesion in the lower esophagus. Endoscopic submucosal dissection was performed on both lesions, since neither distant nor lymph node metastases were identified. Histological examination showed gastric tubular adenocarcinoma and esophageal squamous cell carcinoma. Immunohistology revealed that cells from neither cancer expressed gastrin, gastrin receptor, or p53. Whole-exome sequencing showed 8 gene mutations in the esophageal cancer and 6 mutations in 5 genes in the gastric cancer. The reason for the lack of p53 immunostaining was that TP53 was mutated in these cancers, although TP53 mutations differed. Thus, TP53 mutations may not be detected by immunostaining alone. When treating patients with AIG/PA, clinicians must be aware of the possibility of esophageal cancer coexisting with gastric cancer.

The spectrum of esophagitis in patients living with HIV - a scoping review.

Esophageal lesions are common findings in disorders of the digestive tract in patients living with HIV, the most typical symptoms being odynophagia and/or dysphagia. This article provides a narrative review of the spectrum of esophagitis in patients living with HIV, focusing on fungal, viral, bacterial and non-infectious etiologies, as well as co-infections with viral hepatitis viruses. The article provides a comprehensive approach to the strategy of diagnosis and the role of upper digestive endoscopy and histopathological examination in the evaluation of esophageal pathology in patients living with HIV.

Deep Learning for Histopathological Assessment of Esophageal Adenocarcinoma Precursor Lesions

Histopathological assessment of esophageal biopsies is a key part in the management of patients with Barrett esophagus (BE) but prone to observer variability and reliable diagnostic methods are needed. Artificial intelligence (AI) is emerging as a powerful tool for aided diagnosis but often relies on abstract test and validation sets while real-world behavior is unknown. In this study, we developed a 2-stage AI system for histopathological assessment of BE-related dysplasia using deep learning to enhance the efficiency and accuracy of the pathology workflow. The AI system was developed and trained on 290 whole-slide images (WSIs) that were annotated at glandular and tissue levels. The system was designed to identify individual glands, grade dysplasia, and assign a WSI-level diagnosis. The proposed method was evaluated by comparing the performance of our AI system with that of a large international and heterogeneous group of 55 gastrointestinal pathologists assessing 55 digitized biopsies spanning the complete spectrum of BE-related dysplasia. The AI system correctly graded 76.4% of the WSIs, surpassing the performance of 53 out of the 55 participating pathologists. Furthermore, the receiver-operating characteristic analysis showed that the system’s ability to predict the absence (nondysplastic BE) versus the presence of any dysplasia was with an area under the curve of 0.94 and a sensitivity of 0.92 at a specificity of 0.94. These findings demonstrate that this AI system has the potential to assist pathologists in assessment of BE-related dysplasia. The system’s outputs could provide a reliable and consistent secondary diagnosis in challenging cases or be used for triaging low-risk nondysplastic biopsies, thereby reducing the workload of pathologists and increasing throughput.

Radiotherapy improved the efficacy of immunotherapy for advanced esophageal cancer.

e16063 Background: The development of immunotherapy has changed treatment methods for advanced esophageal cancer (EC).However, the efficacy of ICIs in advanced EC is not ideal, and the clinical research on the combination of ICIs and Radiotherapy(RT) in advanced EC remains insufficient. This study aimed to evaluate the effectiveness and safety of radiation in first-line immunotherapy for advanced EC. Methods: We conducted 201 advanced EC patients who received first-line ICIs in West China Hospital. The enrolled patients were divided into 2 groups based on whether they received radiation therapy. Results: The analysis included data from 201 patients. The radiotherapy (RT) group had 103 patients (51.2%), whereas the non-radiotherapy (NRT) group included 98 individuals (48.8%). The RT sites include esophagus lesions (83, 80.6%), metastatic lymph nodes (11, 10.7%), liver metastases (4, 3.9%), bone metastases (2, 1.9%), brain metastases (2, 1.9%), lung metastases(1, 0.97%). The median radiation dose was 50.4 Gy (range, 12-68). The RT group had a median OS of 22.8 months (95% CI, 17.8-NA), which was longer than the NRT group's 14.6 months (95% CI, 12.8-26.5) (p = 0.038). And the median PFS was 12.9 months (95% CI, 11.2-14.0) in the RT group versus 7.3 months (95% CI, 6.3-9.7) in the NRT group (p = 0.006). Patients in the RT group had a higher disease control rate (DCR) (99.0% vs. 76.5%, P &lt; 0.001). However, a higher proportion of patients in the RT group developed grade 3-4 myelosuppression (37.86% V.S. 20.20%, P = 0.006), and there was no significant difference in the other AEs. Conclusions: In the first-line immunotherapy for advanced esophageal cancer, radiotherapy has been attributed to improved survival with tolerable toxicity.

Camrelizumab plus chemotherapy combined with consolidative radiotherapy as first-line treatment for oligometastatic esophageal squamous cell carcinoma (ESCORT-1st-RT): A single-arm, open-label, phase 2 trial.

e16043 Background: Compared to chemotherapy alone, immunotherapy combined with chemotherapy as the first-line standard treatment for esophageal squamous cell carcinoma (ESCC) can increase progression-free survival (PFS) to 5.8-7.2 months. This study aimed to explore the feasibility and safety of combining camrelizumab and chemotherapy with consolidative radiotherapy in the treatment of advanced oligometastatic ESCC. Methods: This study included newly diagnosed patients with stage IV ESCC confirmed by histopathology and imaging examination who had ≤ 5 metastatic lesions in ≤ 3 organs. All patients were treated with camrelizumab combined with albumin paclitaxel and carboplatin for 4 cycles, followed by consolidative radiotherapy. The primary esophageal lesion and metastatic lymph nodes were treated with involved-field irradiation therapy, receiving 2.0 Gy per fraction over 25 daily sessions. For distant metastases in organs like the liver, lungs, brain, or bones, radiotherapy was tailored to individual clinical needs, often employing hypofractionated radiation therapy with doses starting at 3 Gy per fraction or above. The maintenance duration of camrelizumab treatment was limited to a maximum of 12 months. The primary endpoint was PFS. The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 26, 2021, to September 28, 2022, 29 patients with ESCC, median age 63 (range 51-74), were enrolled; 93.1% were male. All had an ECOG score of 0 or 1 and stage IV disease. 27 (93.1%) patients completed planned radiotherapy. Of 29 evaluated patients, 23 achieved an objective response and 6 maintained stable disease. Thus, the ORR and DCR were 79.3% (95% CI 78.2-80.4) and 100% (95% CI 100-100), respectively. With 23.3 months (95%CI 21.5-25.1) of follow-up, the median PFS was13.7 months (95% CI 9.9-17.5) , the median OS has not reached and the 1-year and 2-year OS rates were established at 72.4% (95% CI 52.3-85.1) and 61.4% (95% CI 41.1-76.5), respectively. The most common treatment-emergent adverse events (TEAEs) of grade 3-4 were lymphocyte count decreased (65.5%), neutrophil count decreased (27.6%), and white blood cell count decreased (20.7%). 1 patients discontinued camrelizumab treatment due to radiation esophagitis. No grade 5 TEAEs occurred. Conclusions: Consolidative radiotherapy following camrelizumab combined with chemotherapy showed potential efficacy and manageable tolerability in patients with advanced oligometastatic ESCC.