bluuebunny/crossref_metadata_2025 huggingface dataset:
31. MULTICENTER RANDOMIZED CLINICAL TRIAL OF CRT VS DCF AS INITIAL TREATMENT FOR SUBSEQUENT CONVERSION SURGERY FOR CLINICAL T4B ESOPHAGEAL CANCER
Authors: Sugimura Keijiro , Miyata Hiroshi , Tanaka Koji , Makino Tomoki , Takeno Atsushi , Shiraishi Osamu , Motoori Masaaki , Yamasaki Makoto , Hirao Motohiro , Fujitani Kazumasa , Yasuda Takushi , Yano Masahiko , Doki Yuichiro
Published: August 2023

Backgroud

Although induction followed by conversion surgery (CS) is potentially curative for T4b esophageal cancer, the optimal initial induction treatment is unclear. We conducted a multicenter randomized prospective phase 2 trial of chemoradiotherapy (CRT) versus chemotherapy (CT) as initial induction therapy for CS in clinical T4b esophageal cancer. We compared treatment effects, adverse events and survival.

Methods

Ninety-nine patients with T4b esophageal cancer were randomly allocated to chemoradiotherapy (Group A, n = 49) or CT (Group B, n = 50) as initial induction treatment. CRT consisted of radiation (50.4 Gy) with cisplatin and 5-fluorouracil. CT consisted of 2 cycles of docetaxel plus cisplatin and 5-fluorouracil (DCF). CRT or CT was followed by CS if resectable. If unresectable, the patient received the other treatment as secondary treatment. CS was performed if resectable after secondary treatment. The primary end point was 2-year overall survival. The Japan Registry of Clinical Trials (s051180164).

Results

In Group A, CS was performed in 34 (69%) and 7 patients (14%) after initial and secondary treatment. In Group B, CS was performed in 25 (50%) and 17 patients (34%) after initial and secondary treatment. The R0 resection rate after initial and secondary treatment was similar (78% vs 76%, P = 1.000). Adverse events including leukopenia, neutropenia, febrile neutropenia, and diarrhea were significantly more frequent in Group B. Group A had better histological complete response of the primary tumor (40% vs 17%, P = 0.028) and histological nodal status (P = 0.038). The 2-year survival rate was 55.1% (95% CI 41.1–68.3%) in the CRT group and 34.7% (95% CI 22.8–48.9%) in the CT group, although the difference was not significant (p = 0.11). Local and regional lymph node recurrence in patients undergoing R0 resection was significantly higher in CT group than CRT group (30% versus 8%, p = 0.03 and 37% versus 8%, p = 0.002, respectively).

Conclusions

The results of the present trial showed that upfront CRT was superior to upfront CT in terms of adverse effects, pathological effects and 2 year-overall survival as initial induction therapy for CS in clinical T4b esophageal cancer.
136. IMPACT OF SKELETAL MUSCLE LOSS AND SARCOPENIA ON OUTCOMES OF LOCALLY ADVANCED ESOPHAGEAL CANCER
Authors: Xiao Xin , Yuan Yong
Published: August 2023

Background

The impact of change in skeletal muscle and the sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial.

Methods

We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after neoadjuvant chemoradiation. The SMI less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women were defined as sarcopenia. The nonlinearity of the effect of percent change in SMI (ΔSMI%) to survival outcomes was assessed by restricted cubic splines.

Results

Overall, data of 367 patients were analyzed. The survival outcomes between sarcopenia and non-sarcopenia groups had no significant differences before NACR. However, patients in post-NACR sarcopenia group showed poor overall survival (OS) benefit (P = 0.016) and poor disease-free survival (DFS) (P = 0.043). Severe postoperative complications rates were 11.9% in post-NACR sarcopenia group and 5.0% in post-NACR non-sarcopenia group (P = 0.019). The association of ΔSMI% with survival outcomes was nonlinear significantly. On the multivariate analysis of OS, ΔSMI % > 12% was the independent prognostic factor (HR = 1.76, 95%CI: 1.03–2.99, P = 0.039) and significant difference was also found on DFS analysis (P = 0.025).

Conclusion

Patients with post-neoadjuvant chemoradiotherapy sarcopenia have worse survival and adverse short-term outcomes. Moreover, additional skeletal muscle index loss increases risk of death and disease progression during neoadjuvant chemoradiotherapy, and max significant difference was reached when it loss over 12%.
137. THE COMPARISON OF UNIPORTAL VERSUS MULTIPORTAL VIDEO-ASSISTED THORACIC SURGERY FOR ESOPHAGEAL CANCER: A PROPENSITY-WEIGHTED ANALYSIS
Authors: Yuan Yong , Xiao Xin
Published: August 2023

Background

Uniportal video-assisted thoracoscopic surgery (VATS) has been widely used, however, there are few studies on uniportal VATS for esophagectomy.

Methods

Data from patients with clinical stage T1–3/N0/M0 thoracic esophageal cancer who underwent surgery between January 2017 and December 2020 were prospectively enrolled and retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to assess the outcomes.

Results

Overall, 55 patients who underwent uniportal, and 212 patients who underwent multiportal, VATS were identified. Surgery-related postoperative complications (Clavien-Dindo grades 1–2) occurred less frequently after uniportal than multiportal VATS in both crude and IPTW models (8.1% versus 29.3%, respectively; P = 0.009). The median postoperative length of stay was 9 (9–10) days in the uniportal VATS and 10 (9–14) days in the multiportal VATS group (P = 0.025 after IPTW). Upon IPTW analysis, in uniportal and multiportal VATS groups, the rates of pneumonia were 10.6% and 26.9% (P = 0.040), while the rates of anastomotic fistulae (grade 2) were 1.0% and 6.6% (P = 0.036), respectively. The visual analog scale (VAS) was administered on postoperative first 7 days and were significantly lower in the uniportal VATS group (P < 0.001). No surgical mortality was observed in the uniportal VATS group, and the survival benefit between the two groups was comparable before (P = 0.732) and after IPTW (P = 0.542).

Conclusions

Uniportal VATS for esophagectomy resulted in a lower rate of postoperative complications with less postoperative pain, and is practical for treating patients with esophageal cancer.
164. INTRAOPERATIVE LYMPHATIC FLOW MAPPING USING INDOCYANINE GREEN PREDICTS LYMPH NODE METASTASIS IN ESOPHAGEAL CANCER PATIENTS NOT TREATED WITH NEOADJUVANT CHEMOTHERAPY
Authors: Shiomi Shinichiro
Published: August 2023

Background

Lymphatic flow mapping using near-infrared fluorescence (NIR) imaging with indocyanine green (ICG) has been used for the intraoperative prediction of lymph node metastasis (LNM) in various cancers. Previous studies examined the feasibility of applying this technique to patients with esophageal cancer. However, a consistent method that yields sufficient diagnostic quality has yet to be confirmed. This study explored the diagnostic utility of our established lymphatic flow mapping protocol for predicting LNM in esophageal cancer.

Methods

We injected 0.5 mL of ICG (500 μg/mL) into the submucosal layer at four peritumoral points on the day before surgery for 54 patients. We performed lymphatic flow mapping intraoperatively using NIR imaging. After determining the NIR status and presence of metastases, evaluable lymph node stations on intraoperative NIR imaging and all resected lymph nodes were divided into four categories: ICG + meta+ (true positive), ICG + meta− (false positive), ICG − meta+ (false negative), and ICG − meta− (true negative). Logistic regression models were used to investigate the characteristics of patients with LNs or LN stations associated with high false-negative rates.

Results

The distribution of ICG+ and meta+ lymph node stations differed according to the primary tumor site. Sensitivity and specificity for predicting meta+ lymph nodes among ICG+ ones were 50% and 75%, respectively. Predicting meta+ lymph node stations among ICG+ stations improved these values to 66% and 77%, respectively. Undergoing neoadjuvant chemotherapy was an independent risk factor for having meta+ lymph nodes with false-negative diagnoses (odds ratio: 4.82; 95% confidence interval: 1.28–18.19). The sensitivity of our technique for predicting meta+ lymph nodes and meta+ lymph node stations in patients who did not undergo neoadjuvant chemotherapy was 79% and 83%, respectively.

Conclusion

Our NIR imaging protocol potentially helps to predict lymph node metastasis intraoperatively in patients with esophageal cancer undergoing esophagectomy who had not undergone neoadjuvant chemotherapy. This technique may effectively serve as a parameter for assessing the need for dissecting LNs in each station and determining whether it is applicable to reduce the extent of lymphadenectomy.
186. PROGNOSTIC ROLE OF NODAL SKIP METASTASIS IN THORACIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A LARGE-SCALE MULTICENTER STUDY
Authors: Shang Qi-Xin , Chen Long-Qi , Yang Yushang
Published: August 2023

Background

Nodal skip metastasis (NSM) is found in esophageal squamous cell carcinoma (ESCC), however, its prognostic role is controversial. We aimed to investigate the prognostic value of NSM in thoracic ESCC patients.

Methods

NSM was categorized according to the N-groupings of JES staging system, which is tumor location dependent. Using the Kaplan–Meier method and Cox-regression analysis, we retrospectively analyzed the overall survival (OS) in 2325 ESCC patients after radical esophagectomy in three high-volume esophageal cancer centers. Predictive models were also constructed.

Results

The overall NSM rate was 20.0% (229/1141); NSM rate was 37.4%, 12.9%, and 22.2% in upper, middle and lower thoracic ESCC, respectively. Patients with NSM always had better prognosis than those without NSM. Furthermore, NSM was an independent prognostic factor for thoracic ESCC patients (HR = 0.633; 95% confidence interval [CI]: 0.499, 0.803; P < 0.001). By integrating the prognostic value of NSM and N stage, we proposed the New N staging system. The categories defined by the New N staging system were more homogeneous in terms of OS than those defined by the current N system. Moreover, the New N system was shown as an independent prognostic factor for thoracic ESCC patients as well (HR = 1.607; 95%CI: 1.520, 1.700; P < 0.001). Overall, the New N system had a slightly better homogeneity, discriminatory ability, and monotonicity of gradient than the N system.

Conclusions

Our study emphasized the prognostic power of NSM and developed a modified Node staging system to improve the efficiency of the current UICC/AJCC N staging system.
190. PROGNOSTIC VALUE OF COMBINATION OF LYMPHOCYTE-TO-MONOCYTE-RATIO AND CYFRA 21-1 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Yang Yuxin , Liu Zhichao , Jiang Chao , Pan Jie , Yu Boyao , Zhu Kaiyuan , Li Zhigang
Published: August 2023

Background

Previous studies have shown that serum tumor markers and systematic inflammatory and nutritional indicators, including Cytokeratin fragments (CYFRA) 21–1 and the lymphocyte-to-monocyte ratio (LMR), are associated with the prognosis of esophageal malignancies. However, their individual prognostic sensitivity and specificity are not yet sufficient. This study aims to investigate the potential of a combined score (CA-LMR) based on CYFRA 21-1 levels and LMR as a novel prognostic predictor for patients with esophageal squamous cell carcinoma (ESCC).

Methods

A total of 460 consecutive patients underwent oesophagectomy were enrolled, and three groups were established based on CA-LMR score. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan–Meier analysis, and associated factors were analyzed by multivariate Cox analysis. Additionally, modified-pStage (mpStage) was developed based on CA-LMR score, the discriminatory ability, monotonicity, homogeneity and prognosis prediction ability were measured by log-rank χ2, linear-trend χ2, likelihood-ratio χ2 test and Akaike Information Criterion.

Results

The allocation of CA-LMR score of 0, 1 and 2 were 107 (23.3%), 280 (60.9%), and 73 (15.9%). There was a significant association between CA-LMR and male gender (P = 0.001), smaller BMI (P = 0.035), longer tumor lesions (P = 0.002), and high pT, pN, pStage (P < 0.001, P = 0.011, P = 0.001). The 5-year OS for CA-LMR scores of 0, 1, and 2 were 75.4%, 60.2%, and 32.8%, respectively (P < 0.001) (Fig. 1A,B). Multivariate analysis indicated CA-LMR score (P = 0.011) was an independent prognostic factor for OS (Fig. 1C-E). Furthermore, the proposed mpStage system demonstrated superior discriminatory ability, monotonicity, homogeneity and prognosis prediction ability over AJCC 8th pStage system.

Conclusions

The CA-LMR score, combined with tumor marker and inflammatory index, could use as a potential prognostic indicator, moreover, our modified pStage system exhibited superior stratification and prognostic accuracy for patients with ESCC, making it possible to serve as novel reference for clinical management.
193. RORY+ NEUTROPHILS: A NOVEL THERAPEUTIC TARGET IN GASTRO-ESOPHAGEAL ADENOCARCINOMA
Authors: Dhoparee-Doomah Iqraa , Brassard Ariane , Leo Sabrina , Alhujairi Wegdan , Su Xin , Feng Lixuan , Qiu Qian , Kosoy Gregory , Bourdeau France , Giannias Betty , Tchervenkov Jean , Ferri Lorenzo , Cools-Lartigue Jonathan
Published: August 2023

Background

High neutrophil-to-lymphocyte ratio (NLR) is associated with worse oncological outcomes. No current therapies target this emergency myelopoiesis-driven (EM) phenotype. EM, driven by retinoic-acid orphan receptor gamma (RORy), is the phenomenon where cancer cells secrete various factors, skewing normal hematopoiesis towards increased production of pro-tumour RORy+ neutrophils. These neutrophils correlate with advanced stage disease. Additionally, RORy ablation reduces tumour burden in vivo. Our study explores the undescribed roles and therapeutic potential of RORy+ neutrophils in GEA.

Methods: Peripheral blood collected from treatment-naïve GEA patients were lysed and stained for flow cytometry for the following markers: CD66b, CD11b, RORy, interleukin-17 (IL-17) and programmed death-ligand 1 (PD-L1).5x106 YTN16-GFP cells, a murine gastric cancer cell line, were injected in the flank of C57Bl/6 mice. 7 days post-tumour inoculation, 25 mg/kg of a novel experimental RORy inhibitor (Compound #10) was injected subcutaneously on a daily basis till endpoint. Tumour size and circulating NLR were monitored on a weekly basis throughout the experiment. Blood and tumour were also collected at endpoint and stained for flow cytometry.

Results

Our data demonstrate that: Treatment-naïve GEA patients with a high NLR (NLR > 4) have increased prevalence of circulating RORy+ neutrophils compared to low NLR (NLR < 4) GEA patients and healthy volunteers.Circulating RORy+ neutrophils have a higher expression of PD-L1 and IL-17 compared to RORy (−) neutrophils, hinting towards a pro-inflammatory and immunosuppressive phenotype.Anti-RORy treatment in a murine gastric cancer model results in reduced tumour burden and reduced percentage of intratumoural RORy+ neutrophils. Treated mice also exhibited a less immunosuppressive intratumoural microenvironment.

Conclusion

We are the first to associate a high circulating NLR with higher prevalence of circulating RORy+ neutrophils in GEA, thus demonstrating evidence of emergency myelopoiesis in those patients. Additionally, we show that RORy+ neutrophils are a major player in cancer progression. More importantly, these results define a novel therapeutic target that can be utilized to improve patient outcomes, namely GEA patients with a high NLR, a patient subgroup known to have worse outcomes.
202. AN ARTIFICIAL INTELLIGENCE ALGORITHM FOR DETECTION OF CIRCULATING TUMOR CELLS IN PATIENTS WITH ESOPHAGEAL CANCER
Authors: Okumura Tomoyuki , Akashi Takahisa , Terabayashi Kenji , Tanaka Haruyoshi , Yamazaki Takeyoshi , Numata Yoshihisa , Manabe Takahiro , Miwa Takeshi , Watanabe Toru , Hirano Katsuhisa , Hashimoto Isaya , Shibuya Kazuto , Yoshioka Isaku , Yamada Akane , Sasaki Tohru , Fujii Tsutomu
Published: August 2023

Background

Circulating tumor cells (CTCs) are considered predictors of distant metastasis, therapeutic response, and prognosis in various cancer. However, the overall process of detecting these marker expressions in CTCs becomes more complex and time consuming as more markers of cytopathologic heterogeneity are discovered. The aim of this study was to evaluate the use of a convolutional neural network (CNN)-based image processing artificial intelligence (AI) for CTC detection in ESCC patients.

Methods

We first investigated the accuracy of the AI algorithm to distinguish ESCC lines (KYSEs) from peripheral blood mononuclear cells (PBMCs). Then we used the AI algorithm to detect CTCs in peripheral blood samples obtained from ESCC patients.

Results

The AI algorithm discriminated KYSE from PBMCs of healthy volunteers accompanied by EpCAM staining with greater than 99.8% accuracy when the AI was trained on the same KYSE. The average accuracy of the AI and the 4 investigators in the differentiation of KYSE from PBMCs was 100% and 91.8%, respectively (p = 0.011). Average time to complete classification of 100 cell images for AI and human was 0.74 and 630.4 seconds, respectively (p = 0.012). The average number of EpCAM-positive/DAPI-positive cells detected in blood samples by the AI were 44.5 over 10 ESCC patients and 2.4 over 5 healthy volunteers, respectively (p = 0.019).

Conclusion

These results indicate that the CNN-based image-processing algorithm for CTC detection provides higher accuracy and shorter analysis time compared to human, suggesting its clinical application for ESCC patients.
203. SURVIVAL IMPACT OF THORACIC DUCT RESECTION IN PATHOLOGICAL RESPONDERS AFTER TRIPLET CHEMOTHERAPY: EXPLORATORY ANALYSIS FROM MULTICENTER PHASE III TRIAL JCOG1109
Authors: Matsuda Satoru , Takeuchi Hiroya , Kato Ken , Machida Ryunosuke , Tsubosa Yasuhiro , Daiko Hiroyuki , Ozawa Soji , Ogata Takashi , Fukuda Takashi , Fujita Takeo , Abe Tetsuya , Bamba Takeo , Watanabe Masayuki , Kawakubo Hirofumi , Shibuya Yuichi , Otsubo Dai , Kakishita Tomokazu , Hashimoto Naoyoshi , Sasaki Keita , Kitagawa Yuko
Published: August 2023

Purpose

JCOG1109 was a three-arm randomized phase III trial to confirm the survival advantage of docetaxel plus cisplatin plus 5-fluorouracil (DCF) and cisplatin plus 5-fluorouracil (CF) combined with radiotherapy (CF-RT) over CF as preoperative treatment for locally advanced esophageal squamous cell carcinoma. The purpose of this study was to evaluate the survival impact of thoracic duct (TD) resection, and its association with preoperative treatment and pathological response in patients who were enrolled to JCOG1109.

Materials and Methods: Patients with potentially resectable advanced thoracic esophageal cancer were randomly assigned to three preoperative therapies and followed by open or thoracoscopic esophagectomy with regional lymphadenectomy. Clinicopathological factors, surgical results which include the status of TD resection, and survival were compared among groups. Furthermore, the survival impact of TD resection was evaluated in the subgroup based on pathological response and preoperative therapy.

Results

Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200). Of 589 eligible patients to JCOG1109, 541 patients underwent esophagectomy (CF/DCF/CF-RT, 183/181/177). The patients with TD resection showed significantly worse PFS in pathological non-responders, whereas no significant difference in pathological responders. When survival impact of TD resection was evaluated in the subgroup analysis using preoperative treatment and pathological response, patients with TD resection showed significantly better PFS and OS in those who received DCF and achieved pathological response.

Conclusion

Intensive local control with TD resection in esophagectomy might contribute to improve survival in pathological responders after preoperative DCF therapy.
220. INDUCTION CHEMOTHERAPY FOLLOWED BY RESTAGING AND SURGERY FOR ADVANCED ESOPHAGEAL CANCER
Authors: Zijden Charlène , Sluis Pieter , Mostert Bianca , Nuyttens Joost , Spaander Manon , Toxopeus Eelke , Valkema Roelf , Lagarde Sjoerd , Wijnhoven Bas
Published: August 2023

Background

Patients with limited metastatic or advanced esophageal cancer have a poor prognosis and are often referred for palliative care. Induction chemotherapy may be considered as an alternative treatment. In patients with a good radiological response, treatment with curative intent may become feasible. The aim of this study was to assess overall survival (OS) in patients treated with induction chemotherapy.

Methods

Patients with esophageal or junctional cancer who underwent induction chemotherapy for advanced disease between 2003–2021 were identified from an institutional database. Response to induction chemotherapy was assessed by 18F-FDG-PET/CT or conventional CT-scan. Response to therapy and further treatment was discussed in the multidisciplinary tumor board. OS was calculated from date of diagnosis until date of death or last day of follow-up using the Kaplan Meier method. Univariable and multivariable analyses were performed to identify prognostic factors for survival.

Results

Some 238 patients were identified of whom 69% had esophageal adenocarcinoma. The majority of patients were treated with taxane/platinum based chemotherapy (79%). Response evaluation after induction chemotherapy was performed in 233 patients and 127 patients (53%) underwent esophagectomy. Median and 5-year OS after esophagectomy was 26.3 months (95% CI 18.8–33.8) and 29.6%, respectively. Patients who did not undergo surgery had a median OS of 12.6 months (95% CI 10.6–14.7) and 5-year OS rate of 6.4%. cT4b tumor (HR 2.01, 95% CI 1.02–3.92, p = 0.04) and poor tumor differentiation (G3) (HR 1.45, 95% CI 1.02–2.05, p = 0.04) were associated with worse survival.

Conclusion

In selected patients with advanced disease not amendable for standard treatment, induction chemotherapy followed by esophagectomy may achieve a 5-year overall survival of 30%. The presence of cT4b tumor or poor tumor differentiation (G3) were associated with worse survival.
229. WEST-CHINA MODE IN MEDIASTINOSCOPE-ASSISTED TRANSHIATAL ESOPHAGECTOMY: A MORE MATURE AND VERSATILE TRANSHIATAL ESOPHAGECTOMY PROCEDURE
Authors: Yuan Pei-song , Hu Weipeng , Liu Zheng , Wu Na , Lin Haonan , Xia Qi , Li Shiyu , Hu Yang
Published: August 2023

Background

Mediastinoscope-assisted transhiatal esophagectomy (MATHE) is the most minimally invasive esophagectomy procedure. It is a more challenging procedure and more difficult to be popularized than thoracoscopic surgery. We developed a new MATHE operation mode that provides a clearer visual field and makes the procedures simpler.

Methods

A total of 48 patients with esophageal cancer were divided into a control group (n = 29) and a study group (n = 19). The control group underwent classic MATHE, while the study group received modified MATHE. We compared the two groups on operation time; intraoperative blood loss; blood transfusion amount; incidence rate of lung infection, recurrent laryngeal nerves (RLNs) injury, chylothorax, and anastomotic leakage; and upper mediastinal lymph node dissection.

Results

The study group was significantly better than the control group in operation time (273.94 min vs. 322.90 min, p < 0.05), intraoperative blood loss (46.84 mL vs. 68.97 mL, p < 0.05), and left paratracheal lymph node (No. 4 L) dissection rate (84.21% vs. 24.14%, p < 0.01). No significant differences were identified in the incidence rate of anastomotic leakage, lung complications, or RLNs injury between the two groups.

Conclusion

The modified MATHE is easier to perform. Modified MATHE is significantly superior to classic MATHE in operation time, intraoperative blood loss, and upper mediastinal lymph node dissection rate.
244. A NOVEL SERUM GLYCOPROTEIN BIOMARKER PANEL FOR SCREENING OF ESOPHAGEAL ADENOCARCINOMA AND SURVEILLANCE OF BARRETT’S ESOPHAGUS
Authors: Lipscombe Richard , Duong Marisa , Casey Tammy , Fernandez Gareth , Bringans Scott , Peters Kirsten , Hill Michelle , Tan Pearl , Lipscombe Richard
Published: August 2023

Background

Esophageal adenocarcinoma (EAC) has become the predominant type of esophageal cancer in Western countries and Barrett’s esophagus (BE) is the only known precursor of EAC. Early diagnosis and intervention of EAC significantly reduces the disease mortality. Endoscopic surveillance in patients with BE is costly and remains controversial as an EAC screening test at the population level. This study aims to develop a simple blood test to allow close surveillance of EAC in patients with BE and screening EAC at a large population level.

Methods

A total of 298 serum samples were obtained from two independent cohorts recruited in Australia (N = 249) and the US (N = 49) from four groups: healthy controls, BE-low/no dysplasia, BE-high dysplasia and EAC. Thirty-three candidate glycoprotein peptides were measured by mass spectrometry after lectin pulldown. The Australian cohort was used as the development cohort. Multivariate logistic regression was used to develop diagnostic models to distinguish different disease status, followed by a forward stepwise approach. Diagnostic models were further validated in the US cohort. Model performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC) and sensitivity, specificity of each model determined.

Results

Seven glycoproteins were found to be significantly associated with EAC. A series of diagnostic models were developed to distinguish different disease status, with AUCs ranging from 0.72 to 0.84 in the development cohort and from 0.79 to 0.94 in the validation cohort. After adjusting for age and sex, biomarker models showed good discrimination and can distinguish patients with EAC from control group (AUC = 0.75 in development cohort and AUC = 0.94 in validation cohort). Biomarker models can also distinguish patients who require endoscopic interventions (including patients with EAC and BE with high dysplasia) from participants in the control group (AUC = 0.72 in development cohort and AUC = 0.79 the validation cohort).

Conclusion

A panel of serum glycoprotein biomarkers were identified associated with EAC and BE with high dysplasia, with good discrimination of disease status. These biomarkers have potential utility as a simple blood test that could be used for screening EAC in a large population, and for surveillance disease progression in patients with BE.
254. THE IMPACT OF D2 VERSUS D1 LYMPHADENECTOMY IN SIEWERT II GASTROESOPHAGEAL JUNCTION (GEJ) CANCER
Authors: Alcasid Nathan , Banks Kian , Fink Deanna , Susai Cynthia , Barnes Katherine , Wile Rachel , Sun Angela , Patel Ashish , Ashiku Simon , Velotta Jeffrey
Published: August 2023

Background

Though a myriad of multimodal treatment options exist for gastroesophageal junction (GEJ) cancer, surgical resection remains the mainstay for potential cure. Extended nodal dissection with a D2 lymphadenectomy (LAD) beyond the D1 peri-gastric dissection remains controversial for Siewert II GEJ cancer. Though D2 LAD may lead to increased lymph node harvest, its effect on overall survival remains elusive. We hypothesize that additional D2 dissection in Siewert II GEJ cancer does not lead to increased survival.

Methods

We reviewed Siewert II GEJ cancer patients who received either a D1 or D2 LAD after receiving neoadjuvant chemoradiation or perioperative chemotherapy from 2012 through 2022. Chi-square and Fisher exact tests were used to compare categorical variables and two-sample Wilcoxon rank sum tests for non-normally distributed continuous variables. The main outcomes measured were 1-year mortality from date of diagnosis, number of nodes sampled, and operative time.

Results

Among the 155 patients identified, 75% of Siewert II underwent a D1 and 25% underwent a D2 LAD. Patients with a D2 LAD more often had >15 lymph nodes harvested than D1 (83% vs 48%, p < 0.001) but had no significant difference in median number of positive nodes (Figure 1). Patients with a D2 LAD had a median operative time approximately 2 hours longer than D1, 362 min vs 244 min (p < 0.001). On multivariable logistic regression adjusting for patient and clinical characteristics, there was no significant difference in 1-year mortality from patients undergoing a D2 vs D1 LAD.

Conclusion

Despite the associated high mortality associated with gastroesophageal junction (GEJ) cancer, there remains little consensus guidelines regarding the optimal preoperative and operative management. Though D2 LAD may theoretically lead to more lymph node harvest, its role in staging may be unnecessarily excessive as there is no gain in number of positive nodes leading to increased operative morbidity with no significant change in survival.
258. A VIDEO-UPDATE OF THE LEARNING CURVE OF THE INTRODUCTION OF MINIMALLY INVASIVE TRANSCERVICAL ESOPHAGECTOMY (MICE)
Authors: Klarenbeek Bastiaan , Fujiwara Hitoshi , Kramer Fleur , Veenendaal Linde , Shiozaki Atsushi , Rosman Camiel
Published: August 2023

Background

A radical esophagectomy is considered the cornerstone of a curative treatment strategy for esophageal cancer. However, transthoracic approaches are associated with high morbidity rates, even in expert centers. Pulmonary complications and anastomotic leakage are the most frequent and have the most impact. In the pursuit to improve clinical outcomes for patients with esophageal cancer, reducing post-operative complications is essential.

Methods

Minimally Invasive trans-Cervical Esophagectomy (MICE) is an innovative surgical technique, combining a single-port trans-cervical mediastinal dissection with a laparoscopic transhiatal esophagectomy. This approach facilitates a radical esophagectomy and a two- or three-field lymphadenectomy, while avoiding a thoracoscopy/thoracotomy. Therefore, MICE could reduce pulmonary complications and the consequences of anastomotic leakage, without compromising oncological radicality. Reducing post-operative complications will impact mortality, quality of life, long-term survival, and costs.

Results

The first MICE procedure in a Dutch esophageal cancer patient was performed at Radboudumc in January 2021, after an extensive pre-clinical trajectory. Subsequently a prospective pilot study was conducted in 20 consecutive patients undergoing MICE. The primary outcome, pulmonary complication rate, was 15% (3/20), which is substantially lower than after transthoracic minimally invasive esophagectomy (TMIE). Recurrent laryngeal nerve palsy (RLNP) occurred in seven (35%) cases, of which six recovered spontaneously, and this is in concordance with the results of Japanese series. Anastomotic leakage occurred in 15% of patients, which is in similar to our national benchmark of 18%.

Conclusion

We would like to share one of our latest surgical videos of MICE during our learning curve. Probably this will be around consecutive case number 70.
261. THE PROGNOSTIC IMPACT OF PRE-OPERATIVE NUTRITIONAL INDICATORS OF THE PATIENTS WITH ESOPHAGEAL CANCER
Authors: Kao Chia-Cheng , Chen Ke-Cheng , Huang Pei-Ming , Lin Mong-Wei , Kuo Shuenn-Wen , Cheng Chia-Hsien , Hsu Feng-Ming , Huang Ta-Chen , Hsu Hsao-Hsun , Lee Jang-Ming
Published: August 2023

Background

Esophagectomy with or without concurrent chemoradiotherapy had been the treatment of choice for the patients with clinically operable esophageal cancer. In addition to the standard TNM status of the disease, it is unknown about whether pre-operative nutrition indicators, inclusive of hemoglobin value and albumin level before treatment, will have impact on post-operative survival outcome of these patients.

Methods

This is a retrospective study from a single medical center. We retrospectively reviewed and analyze the survival impact of various pre-operative nutritional indicators of esophageal cancer patients who received esophagectomy. Pre-operative indicators included age, gender, receiving concurrent chemoradiotherapy or not, alcohol, betel nuts and cigarette usage or not, lung function test, Hemoglobin value, Albumin level and white blood cell level. The survival impact of these parameters was evaluated with univariate as well as multi-variate analysis.

Results

Our study had totally retrospectively reviewed 1213 patients, which received esophagectomy between 1996 to 2022. Ratio of Male to Female is 1112 to 111, and 325 patients are older than 65 years old. Before operation, 746 among 1213 patients had received concurrent chemoradiotherapy. In univariate analysis, we found that Pre-operative Hemoglobin value (cut-off point 11.9) and Albumin level (cut-off point 4.1) had statistically significant difference on overall survival, with increased risk of mortality by the presence of lower level of Hb and albumin with P-value <0.001. The survival difference persisted after adjusted with TNM status under multi-variate analysis.

Conclusion

Our study showed that Pre-operative Hemoglobin value and Albumin level can be a significant prognosis factor of esophageal cancer patients who received esophagectomy. This significant result highlight the importance of nutritional status in caring the patients of esophageal cancer and suggested the possibility of improvement of survival by intervention of malnutrition during the course of treatment for esophageal cancer.
263. DUPILUMAB EFFICACY AND SAFETY TO 52 WEEKS IN ADULT AND ADOLESCENT PATIENTS WITH EOSINOPHILIC ESOPHAGITIS: RESULTS FROM LIBERTY EOE TREET
Authors: Dellon Evan , Rothenberg Marc E , Collins Margaret , Hirano Ikuo , Chehade Mirna , Bredenoord Albert J , Lucendo Alfredo J , Spergel Jonathan M , Sun Xian , Hamilton Jennifer D , Mortensen Eric , Glotfelty Lila , Shabbir Arsalan
Published: August 2023

Background

In Parts A and B of the 3-part, phase 3 LIBERTY EoE TREET study (NCT03633617), dupilumab 300 mg weekly (DPL qw) vs placebo (PBO) demonstrated significant efficacy and acceptable safety up to 24 weeks in adults and adolescents with eosinophilic esophagitis (EoE). Patients who completed Parts A and B entered Part C and received DPL qw to 52 weeks. Here we present 52-week results from patients who completed Part B and continued to Part C.

Methods

Of 80 DPL qw patients in Part B, 74 continued DPL qw in Part C (DPL/DPL). Of 79 PBO pts in Part B, 37 patients received DPL qw in Part C (PBO/DPL). Part B co-primary endpoints were proportion of patients achieving peak esophageal intraepithelial eosinophil (eos) count ≤6 eos/high- power field (hpf) and absolute change from Part B baseline in Dysphagia Symptom Score (DSQ) score at Week 24. Key secondary endpoints are listed in the Table. In Part C, all co-primary and secondary endpoints were assessed at Week 52 as secondary endpoints. Safety was also assessed.

Results

At Week 52, 84.6% of DPL/DPL and 67.6% of PBO/DPL patients achieved peak eos count ≤6 eos/hpf; mean (SD) absolute change from Part B baseline in DSQ score was −30.26 (15.39) for DPL/DPL and − 27.25 (11.46) for PBO/DPL patients. At Week 52, 100% of DPL/DPL and 78.4% of PBO/DPL patients achieved peak eos count <15 eos/hpf, 30.8% of DPL/DPL and 16.2% of PBO/DPL patients achieved peak eos count ≤1 eos/hpf, and compared to Part B baseline, peak eos count, EREFS, and HSS grade and stage scores were reduced (Table). DPL demonstrated an acceptable safety profile.

Conclusion

DPL qw demonstrated persistent improvements in clinical, symptomatic, histologic, and endoscopic features of EoE up to 52 weeks and had an acceptable safety profile. PBO patients from Part B who received DPL in Part C showed similar efficacy to dupilumab qw patients of Part B.
269. CURRENT STATUS OF THE INTRODUCTION PROCESS OF MINIMALLY INVASIVE TRANSCERVICAL ESOPHAGECTOMY (MICE), TYPICALLY IDEAL 2A STRUGGLES
Authors: Klarenbeek Bastiaan , Veenendaal Linde , Rosman Camiel
Published: August 2023

Background

The introduction of a novel complex surgical technique is a challenging process and can be associated with a long learning curve and learning-associated morbidity. In order to introduce Minimally Invasive transCervical Esophagectomy (MICE) in a safe way, the IDEAL framework was a used.

Method

MICE is an innovative surgical technique, combining a single-port transcervical mediastinal dissection with a laparoscopic transhiatal esophagectomy. MICE could reduce pulmonary complications and the consequences of anastomotic leakage, without compromising oncological radicality. Our five-step approach of the ‘pre-clinical stage 0’ made the IDEAL framework more applicable as a practical guideline and led to a safe ‘first-in-human procedure, IDEAL stage 1’. Currently we are prospectively collecting data of a single-center Radboudumc cohort, going through the learning curve and finetuning the surgical technique, which is typical for IDEAL stage 2A ‘Development’.

Results

In another abstract, the clinical outcomes of our single-center Radboudumc learning curve cohort will be presented. By the time of the 2023 ISDE conference, around 70 cases will be included. As a result of technical difficulties during the learning curve and succinct evaluation with peers and patients, several changes to the MICE procedure have been made, like: indications, cervical incision, continuous NIM, sequence of abdominal/cervical approach, camera system, extraction and reconstruction, conversion, surgical team.

Conclusion

The surgical technique of MICE evolved during the collection of a singe-centre Radboudumc learning curve cohort. These changes are typical for the ‘IDEAL development stage 2A’, thorough evaluation of these changes might help limiting learning associated morbidity.
277. SIMPLE METHOD: INGUINAL LYMPHANGIOGRAPHY FOR POSTOPERATIVE CHYLOTHORAX
Authors: Ken Ito , Hirotaka Ishida , Akira Jingu , Ryosuke Nogawa , Yoshikatu Saito , Hideki Ota , Hidekazu Matsumoto , Ishiyama Tomoharu
Published: August 2023

Background

Chylothorax is a well-known complication of esophageal cancer surgery, with an incidence of approximately 1–3%. The main cause is intraoperative damage to the thoracic duct, which is often discovered after postoperation. If conservative treatment is chosen, lymphangiography with Lipiodol is the diagnostic and embolization procedure for exposed areas. Itkin et al. reported that improvement rate is approximately 70%. Pedal lymphangiography has been used in the past, but we perform lymphangiography from the inguinal lymph node.

Method

We inject lipiodol under ultrasound guidance.

A total of 6–10 mL injected into each bilateral inguinal lymph node.

The lipiodol drain upstream from the main lumbar lymphatic trunk and contrasts into the thoracic duct under fluoroscopy.

CT scans would be useful in the case that contrasts were unclear.

Result

If it is possible to inject lipiodol into the inguinal lymph nodes, even the thoracic ducts can be easily detected. With the classical method, an incision must be made between the first and second toes under local anesthesia, and minute lymph ducts must be identified and injected. However, if the inguinal lymph nodes are small, the drug tends to leak easily. Leakage is immediately detectable by fluoroscopy, so large leakage is unusual. If the drug is absorbed slowly, it remains subcutaneously after several months and can be identified as an artifact on abdominal X-rays or CT.

Conclusion

Lymphangiography from the inguinal lymph node is a relatively safe and simple method of examination, compared to the intervention from the dorsal foot. No skin incision on the dorsal foot is required, only an echo guided puncture is necessary. The examination time is short, and the patient burden is low. The procedure is not particularly difficult, so it can be performed even at small hospitals.
279. ENDOSCOPIC RENDEZVOUS TECHNIQUE FOR RECANALIZATION OF COMPLETE ESOPHAGEAL OBLITERATION
Authors: Tangkullayanone Watsaphon , Swangsri Jirawat
Published: August 2023

Background

Radiation-induced esophageal stricture is a common late complication following radiation treatment for esophageal cancer or head and neck cancer. Currently, treatments for esophageal stricture are typically minimally invasive, as opposed to surgical reconstruction. However, this condition can significantly impact a patient’s quality of life during treatment including multiple sessions of dilatation, prolonged use of a nasogastric tube or gastrostomy status. In severe cases, complete esophageal obliteration can occur. The patients’ symptoms experienced are more severe than those in ordinary cases, marking endoscopic interventions more challenging and having a higher failure rate.

This case report aims to demonstrate the use of the rendezvous technique in endoscopic treatment for the recanalization of the esophagus.

Methods

A 61-year-old female presented with dysphagia for two years. The patient had a history of hypopharyngeal cancer and underwent concurrent chemoradiation. During surveillance, the patient’s symptoms had worsened, and she was unable to eat or even swallow her own saliva. Endoscopic findings had shown complete esophageal obliteration, and a gastrostomy was performed. An endoscopic intervention was planned to use a two-team approach involving antegrade and retrograde endoscopy. The obstruction part was located at the upper thoracic esophagus using both endoscopes and esophagography. A retrograde guidewire was cannulated from the distal esophagus under fluoroscopic guidance. The guidewire position was checked from multidimensional fluoroscopic views to avoid false tract cannulation. Once the guidewire was nearly passed through the esophageal fibrotic septum, a stricturoplasty was performed from the antegrade endoscope. The guidewire was retrieved from the antegrade endoscope out of the oral cavity, and the esophagus was dilated with Savary-Gilliard dilators and a CRE balloon. A nasogastric tube was placed under direct endoscopic view.

Results

The procedure was successful, and the patency to the esophageal lumen was achieved. The patient’s symptoms improved, there was a decrease in saliva pooling. The patient was scheduled for serial dilatation of the esophagus to maintain luminal patency.

Conclusion

Endoscopic rendezvous technique is a safe therapeutic option for short-segment complete esophageal obliteration. Despite the complex procedure and multidisciplinary approach required, this technique can recanalize the esophageal lumen and avoid the need for surgical reconstruction.
312. H ANASTOMOSIS IN MECKOWN ESOPHAGECTOMY FOR THE REDUCED ANASTOMOTIC LEAKAGE, OBSTRUCTION, AND GASTROESOPHAGEAL REFLUX
Authors: Wu Na , Xia Qi , Hu Yang
Published: August 2023

Background

Anastomotic Leakage, obstruction, and gastroesophageal reflux are the major conditions to be taken into account during restoration of alimentary transit in Meckown esophagectomy. There are numerous types of anastomosis techniques to achieve different emphases while the optimal one has not been established. The outcomes of the novel H anastomosis and the conventional end to end layered anastomosis were explored in a prospective cohort study.

Methods

Patients with resectable esophageal cancer underwent Meckown esophagectomy applying end to end layered anastomosis (Conventional group) or H anastomosis (H group) were included. Besides demographic information, the incidence of anastomotic leakage and other major complications were also recorded. The incidence and severity of postoperative digestive symptoms were assessed by a standard questionnaire including Mellow-Pinkas score for dysphagia and reflux frequency at 6 months after surgery. 24 h-PH and impedance surveillance was also performed on patients receiving H anastomosis.

Results

Of the 122 eligible patients, 88 received end to end layered anastomosis and 34 underwent H anastomosis respectively. 3(3.4%) patients underwent anastomotic leakage in Conventional group and 1(2.9%) in H group (P = 0.897) The incidences of other perioperative complications were comparable between two groups. The H anastomosis was associated with lower incidence of gastroesophageal reflux (17.2% vs 35.8%, P = 0.117) and higher proportion of patients without food solidity limitation (Mellow-Pinkas score = 0) (79.4% versus 69.1% P = 0.305). The DeMeester score extracted from 24 h-PH and impedance surveillance showed the H anastomosis achieved 70% objective reflux free rate.

Conclusion

H anastomosis is a refinement of intussusception anastomosis and layered anastomosis to preserve the anti-reflux function of one-direction valve formed by intussuscepted tissues, leakage free from the different locations of layers of anastomosis and obstruction prevention from the removal of intussuscepted muscular layer of esophagus and seromuscular layer of stomach. A multicenter randomized trial comparing the outcomes of the H anastomosis and end to end anastomosis is in process to validate these conclusions.
318. THE INFLUENCE OF AGE IN OESOPHAGEAL CANCER TREATMENT DECISIONS: A MACHINE-LEARNING APPROACH
Authors: Thavanesan Nav , Farahi Arya , Walters Zoe , Underwood Timothy , Vigneswaran Ganesh
Published: August 2023

Background

Although patient age plays a crucial role in determining curative treatment options for Oesophageal cancer (OC), the exact extent of its influence is not well defined. We used a computational machine learning (ML) approach to model the impact of age in combination with other key decision drivers, such as tumour and patient characteristics, on the likelihood of receiving different types of curative treatment.

Methods

Retrospective analysis of 399 OC patients undergoing curative treatment between 2010–2020 at our tertiary unit. A random forests (RF) classifier model was trained to predict curative treatment decisions for OC patients (neoadjuvant chemotherapy (NACT) and surgery, neoadjuvant chemoradiotherapy (NACRT) and surgery or surgery alone). Variable importance and Partial Dependence analyses were used to assess the importance of age in the model, its influence on treatment decisions, and how that relationship was affected with other decision driver co-variates.

Results

Variable importance analysis confirmed age as most important in the RF model, (26% of total model performance). Partial dependence analysis demonstrate that predicted base probabilities for receiving surgery and NACT changed significantly in older patients. Patients above 70 years had a substantially higher probability of receiving curative surgery and lower probability of NACT. Moreover, the probability of receiving Surgery and NACT is driven by disease characteristics (T and N staging) in patients <70 years but age becomes increasingly important in predicting a surgical decision >70 years. The base probability of surgery and NACRT decisions was also influenced by performance status and age, but only age for NACT patients.

Conclusion

We have successfully applied ML modelling combined with partial dependence analysis to delineate the relationship between age and OC MDT treatment decisions. Age heavily influences curative decisions in OC patients but plays a greater role in patients with specific tumour characteristics. This study provides the basis for exploring subconscious decision drivers and allows teams to address any health inequality.