bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt; 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 &lt; 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

Abstract

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 &lt; 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 &lt; 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

Abstract

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 &gt; 4) have increased prevalence of circulating RORy+ neutrophils compared to low NLR (NLR &lt; 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.05), intraoperative blood loss (46.84 mL vs. 68.97 mL, p &lt; 0.05), and left paratracheal lymph node (No. 4 L) dissection rate (84.21% vs. 24.14%, p &lt; 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

Abstract

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

Abstract

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 &gt;15 lymph nodes harvested than D1 (83% vs 48%, p &lt; 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 &lt; 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

Abstract

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.