bluuebunny/crossref_metadata_2025_split huggingface dataset:
227. DETERMINING SEVERITY OF ESOPHAGEAL ANASTOMOTIC LEAK IN PATIENTS AFTER ESOPHAGECTOMY: DEVELOPMENT OF THE SEAL SCORE
Authors: Ubels Sander , Verstegen Moniek , Bouwense Stefan , Hannink Gerjon , Siersema Peter , Klarenbeek Bastiaan , van Workum Frans , Rosman Camiel ,   on Behalf of the TENTACLE - Esophagus Collaborative Group
Published: September 2022

Abstract
Anastomotic leak (AL) is a common and severe complication after esophagectomy, but it is largely unknown how to assess leak severity when diagnosed. We aimed to develop the Severity of Esophageal Anastomotic Leak (SEAL) score, a tool to determine leak severity at diagnosis of AL.
The TENTACLE—Esophagus study is an international, retrospective cohort study in 71 centres worldwide and included patients with AL after esophagectomy between 2011 and 2019. The primary endpoint was 90-day mortality. To develop the SEAL score, multivariable logistic regression was performed to determining 90-day mortality risk. Leak-related parameters at diagnosis identified as prognostic factors were included as predictors for the SEAL score. Four classes of leak severity were defined (mild, moderate, severe and critical) and the score was internally validated. The study protocol is accessible at www.tentaclestudy.com.
1509 patients with AL were included and the 90-day mortality rate was 11.7%. Twelve leak-related predictors factors were included in the SEAL score, including post-operative day of diagnosis, leucocyte count, organ failure, defect circumference and presence of intrathoracic fluid collections. The score showed good calibration and discrimination with a c-index of 0.77 (95%CI 0.73–0.81). More severe leaks were associated with significant increase in length of (intensive care unit (ICU)) stay, healing time, Comprehensive Complication Index (CCI) and Esophagectomy Complications Consensus Group (ECCG) classification (Table 1). The SEAL score was incorporated in an online tool for use in individual cases: https://www.tentaclestudy.com/seal-score.
The SEAL score grades leak severity into four classes based on individual predictions of 90-day mortality by combining 12 leak-related predictors. The SEAL score also reflected morbidity and can be used to assess AL severity, may guide treatment decisions and may be used in research on AL.
239. EVALUATION OF SUBCARINAL LYMPH NODE DISSECTION AND METASTASIS IN TRANSMEDIASTINAL RADICAL ESOPHAGECTOMY
Authors: Shibamoto Jun , Fujiwara Hitoshi , Konishi Hirotaka , Shiozaki Atsushi , Ohashi Takuma , Kubota Takeshi , Shimizu Hiroki , Arita Tomohiro , Yamamoto Yusuke , Morimura Ryo , Kuriu Yoshiaki , Ikoma Hisashi , Otsuji Eigo 
Published: September 2022

Abstract
The aim of the present study was to evaluate subcarinal lymph node dissection in transmediastinal radical esophagectomy and subcarinal lymph node metastasis in patients with esophageal cancer and to identify predictive factors for subcarinal lymph node metastasis.
Three hundred and twenty-three patients with primary esophageal cancer who underwent transmediastinal or transthoracic esophagectomy with radical two- or three-field lymph node dissection were retrospectively investigated. The clinicopathological characteristics of patients with subcarinal lymph node metastasis were analyzed in detail.
The median number of dissected subcarinal lymph nodes in transmediastinal and transthoracic esophagectomy groups was 6 and 7, respectively, and there was no significant difference between the two groups (p = 0.12). Of all patients, 26 (8.0%) were pathologically diagnosed as positive for subcarinal lymph node metastasis. By univariate analysis, subcarinal lymph node metastasis was found in larger (≥ 30 mm) and deeper (T3/T4a) primary lesions (p = 0.02 and 0.02, respectively), but it was not found in patients (n = 49) with the primary lesion located in the upper thoracic esophagus.
Subcarinal lymph nodes can be dissected in transmediastinal esophagectomy, almost equivalent to transthoracic esophagectomy. The tumor size, depth, and location may be predictive factors for subcarinal lymph node metastasis.
241. A VALIDATED NOMOGRAM PREDICTING LYMPH NODE METASTASIS OF T2N0 ESOPHAGEAL SQUAMOUS CELL CARCINOMA FOR CLINICAL DECISION-MAKING
Authors: Gu Yi-Min , Chen Long-Qi 
Published: September 2022

Abstract
Clinical T2N0 esophageal cancer is the treatment threshold for neoadjuvant therapy. Because of limitations in the diagnostic accuracy of endoscopic ultrasound and positron emission tomography-computed tomography, a number of these patients were verified to have lymph node involvement after esophagectomy. We aimed to develop and validate a nomogram for predicting nodal disease and selecting patients eligible for neoadjuvant therapy.
A predictive nomogram was constructed using the training cohort. We identified patients who underwent esophagectomy for pT2 esophageal squamous cell carcinoma in our department from January 2009 to December 2014. Binary logistic regression was used to determine risk factors for lymph node metastasis. We selected predictors considering both statistical significance and clinical importance. Furthermore, bootstrapping was used to assess the predictive accuracy. An independent cohort from the same institution was used to validate this model. This cohort included consecutive patients with cT2N0 who underwent esophagectomy between January 2015 and April 2019.
The training cohort comprised 551 patients. Logistic regression identified six variables that were associated with lymph node metastasis, including tumor diameter (OR: 2.43, 95% CI: 1.44–4.09; P = 0.001), tumor length (OR: 10.63, 95% CI: 6.32–17.89; P &lt; 0.001), circumferential involvement (OR: 5.14, 95% CI: 6.3–17.9; P &lt; 0.001), differentiation (OR 3.65, 2.24–5.93; P &lt; 0.001), lymphovascular invasion (OR 12.18, 95% CI: 5.91–25.21; P &lt; 0.001), and the presence of multifocal tumors (OR: 8.67, 95% CI: 1.47–51.14; P = 0.017). The C-index was 0.914 (95% CI: 0.889–0.938) in the training cohort and 0.962 (95% CI: 0.939–0.985) in the validation cohort.
A validated nomogram for patients with clinical T2N0 esophageal squamous cell carcinoma may aid in assessing the risk of lymph node metastasis. Neoadjuvant therapy is recommended for high-risk patients.
245. CLINICAL UTILITY OF CTDNA IN LONGITUDINAL MONITORING OF TREATMENT RESPONSES AND RELAPSE IN METASTATIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Ng Hoi Yan , Ko Josephine , Wong Ian Yu Hong , Wong Claudia Lai Ying , Chan Siu Yin , Chan Kwan Kit , Law Tsz Ting , Lam Ka On , Kwong Dora Lai Wan , Law Simon Ying Kit , Lung Maria Li 
Published: September 2022

Abstract
Esophageal squamous cell carcinoma (ESCC) is a deadly cancer frequently diagnosed only at advanced stages, contributing to high mortality. In this study, circulating tumor DNA (ctDNA), which is DNA shed from the tumor into the bloodstream, was utilized for real-time monitoring of treatment response and early detection of relapse using next-generation sequencing. The clinical utility of ctDNA as a biomarker for monitoring disease burden and treatment response was evaluated.
A total of 72 metastatic ESCC patients, who received palliative chemotherapy, were recruited. Blood was collected from the patients before, during, and at the end of treatment. ctDNA was extracted from plasma and the mutation profiles were determined by targeted-capture sequencing using the Roche AVENIO ctDNA expanded 77-genes kit. Mutations or amplification detected in the ctDNA were validated by Sanger sequencing or digital PCR. Mutations in the tumors were validated using formalin-fixed paraffin-embedded (FFPE) tissue with the Roche AVENIO Tumor tissue expanded 77-genes kit.
Single nucleotide variations (SNVs) were detected in 92% and copy number variations (CNVs) were detected in 22% of the metastatic ESCC patients. The most frequently mutated genes were TP53, NFE2L2 and PIK3CA. The presence of TP53 mutations at pre-cycle III treatment was associated with poor progression-free survival and overall survival. Longitudinal ctDNA analysis showed good concordance between mutant allele frequency (MAF) and tumor burden and the change in MAF preceded the radiographic relapse with an average of 46 days. ctDNA also demonstrated the ability to capture inter-tumor heterogeneity in the primary tumor and lymph node metastasis.
Using the 77-gene panel, mutations were detected in ctDNA of metastatic ESCC patients; the change in MAF reflected the tumor burden. Serial analysis of ctDNAs indicates the usefulness of ctDNA as a prognostic and predictive biomarker for real-time non-invasive monitoring to assess tumor burden and to predict treatment efficacy, disease relapse, and patient survival. Mutation profiles in ctDNA may also be useful in guiding personal targeted therapy.
246. MAPPING OF LYMPH NODE METASTASIS FROM THORACIC ESOPHAGEAL CANCER: A RETROSPECTIVE STUDY
Authors: Yang Yafan 
Published: September 2022

Abstract
Objectives: This retrospective study aimed to investigate the optimal extent of dissection for thoracic esophageal cancer(EC) based on the incidence of lymph node metastasis(LNM).
Methods: We retrospectively identified 1,014 patients with thoracic esophageal carcinoma who underwent esophagectomy at our institution between May 2018 and November 2020. Also, the location and rate of LNM in relation to the postoperative pathological results were retrieved. We separately counted the metastasis rates of routinely excised lymph node stations according to the Japan Esophageal Society(JES) staging system.
Results: A total of 1,014 consecutive patients were enrolled. Generally, the rates of LNM in thoracic EC may be arranged in order of station 7 &gt; station 106recR &gt; station 2 &gt; station 106recL. EC in middle and lower thoracic segment also had a high rate of LNM along bilateral recurrent laryngeal nerve. Stations 106tbL and 111 were the lowest frequent sites of metastasis with rate less than 5%, only patients with clinically positive LNs need to dissect. The cT3–4, cN+, or G3 were independent risk factors for LNM and neoadjuvant therapy did not change the distribution.
Conclusions: This study accurately identified the distribution of LNM for thoracic EC patients. And neoadjuvant therapy could not change the overall distribution of LNM in thoracic EC patients. However, whether LNs dissection at stations 106tbL and 111 is related to the survival of thoracic EC or not, needs a long follow-up time to verify.
248. IMPACT OF INCREASING LYMPH NODE YIELD ON STAGING, MORBIDITY AND SURVIVAL AFTER ESOPHAGECTOMY FOR ESOPHAGEAL ADENOCARCINOMA
Authors: Henckens Sofie , Hagens Eliza , van Berge Henegouwen Mark , Meijer Sybren , Eshuis Wietse , Gisbertz Suzanne 
Published: September 2022

Abstract
Extended lymphadenectomy during esophagectomy for esophageal cancer may increase survival, but also increase morbidity. This study analyses changes in lymph node yield over time in a tertiary referral center, and investigates the influence of lymph node yield after transthoracic esophagectomy for esophageal adenocarcinoma on the number of positive lymph nodes, pathological N-stage, complications and survival.
Consecutive patients undergoing transthoracic esophagectomy with gastric conduit reconstruction for esophageal adenocarcinoma between January 2010 and December 2020 were prospectively recorded (follow-up until January 2022). Lymph node yield was analyzed as continuous and dichotomous variable (≤30 vs. ≥31 nodes). The effect of lymph node yield on number of positive lymph nodes, complications, disease-free and overall survival was assessed in multivariable regression analyses.
585 patients were included. Median lymph node yield increased from 25 (IQR 20–34) in 2010 to 39 (IQR 32–50) in 2020. Higher lymph node yield was associated with more positive lymph nodes (≥31 vs. ≤30 IRR 1.39, 95%CI 1.11-1.75). In 258 (y)pN+ patients, the percentage of (y)pN3-stage increased with 14% between patients with ≤30 and ≥ 31 lymph nodes examined (p 0.014). Higher lymph node yield was not associated with more complications. Superior survival was seen in patients with ≥31 vs. ≤30 lymph nodes examined [DFS: HR 0.73, 95%CI 0.58-0.93, OS: HR 0.71, 95%CI 0.55-0.93)].
Lymph node yield increased significantly during the study period, as a result of several changes in the lymphadenectomy technique and separate submission of lymph node stations to pathology. A lymph node yield of ≥31 was associated with upstaging and superior survival after esophagectomy for esophageal adenocarcinoma, without increasing morbidity. Extended lymphadenectomy is therefore a valuable adjunct to multimodal treatment, and should be standard of care in esophageal cancer surgery, irrespective of choice of neoadjuvant therapy.
249. CLINICAL IMPLICATIONS OF CHYLE LEAKAGE FOLLOWING ESOPHAGECTOMY
Authors: Henckens Sofie , Schafrat Pascale , Hagens Eliza , Eshuis Wietse , Gisbertz Suzanne , Laméris Wytze , van Berge Henegouwen Mark 
Published: September 2022

Abstract
For esophageal malignancies, leading oncological centers advocate transthoracic esophagectomy, including routine en-bloc resection of the thoracic duct for adequate mediastinal lymphadenectomy. However, as a result of injury to the main thoracic duct or its collateral branches during resection, this can lead to chyle leakage. The short-term clinical consequences of chyle leakage following esophagectomy are underexposed. The aim of this study was to investigate the clinical implications of chyle leakage following esophagectomy.
This retrospective study of prospectively collected data included patients who underwent transthoracic esophagectomy in 2017–2020. Routinely, the thoracic duct was resected en-bloc as part of the mediastinal lymphadenectomy. Chyle leakage was defined as milky drain fluid for which specific treatment was initiated and/or a triglyceride level in drain fluid of ≥1.13 mmol/l, according to the Esophagectomy Complications Consensus Group classification. Primary endpoints were the clinical characteristics of chyle leakage (type, severity and treatment). Secondary endpoints were the impact of chyle leakage on duration of thoracic drainage and hospital stay.
Chyle leakage was present in 43/314 included patients (14%); of whom 24 (56%) were classified as severity A and 19 (44%) as severity B. All patients were successfully treated with either medium chain triglyceride diet (98%) or total parental feeding (2%). There were no re-interventions for chyle leakage during initial admission, although one patient needed additional pleural drainage during re-admission. Patients with chyle leakage had 3 days longer duration of thoracic drainage (bias corrected accelerated (BCa) 95%CI: 0.46–0.76) and 3 days longer hospital stay (BCa 95%CI: 0.07–0.36), independently of the presence of other complications.
Chyle leakage is a frequently occurring complication following esophagectomy with resection of the thoracic duct and extensive lymphadenectomy, with substantial clinical consequences. Even though non-surgical treatment was successful in all patients with chyle leakage in this series, chyle leakage impeded postoperative recovery. Future research should focus on reducing the incidence of chyle leakage after esophageal surgery.
250. PROGNOSTIC FACTORS ASSOCIATED WITH 18FDG-PET/CT IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER TRIMODALITY TREATMENT
Authors: Feng Wei-Hsiang , Chen Ying Yi , Kuo Yen Shou , Lin Kuan Hsun , Tsai Yuan Ming , Wu Ti Hui , Huang Hsu Kai , Huang Tsai Wang 
Published: September 2022

Abstract
Patients with locally advanced and potentially curable esophageal cancer (EC) should receive trimodality treatment, which involves neoadjuvant concurrent chemoradiotherapy (nCRT) followed by esophagectomy. The maximum standard uptake value (SUVmax) in SUV of 18FDG-PET/CT have been reported to be useful in predicting the prognosis of EC patients treated with nCRT and subsequent esophagectomy. We aimed to determine the pathological response in patients with EC after trimodality therapy and to investigate the prognostic factors associated with SUVmax.
This was a retrospective study of patients with locally advanced esophageal squamous cell carcinoma who received nCRT followed by esophagectomy between January 2011 and December 2018 at the Tri-Service General Hospital in Taipei, Taiwan. Survival analysis was performed using the Kaplan–Meier method and the Cox proportional hazards model. Univariate and multivariate analyses were used to determine the independent prognostic factors.
A total of 79 patients with esophageal cancer underwent esophagectomy, and 50 of them were enrolled in the study. Among the 50 patients enrolled, 18 had a pCR. A post-nCRT maximum standard uptake value (SUVmax) ≥ 3 was a poor prognostic factor associated with OS (hazard ratio [HR]: 3.665, P = 0.013) and PFS (HR: 3.417, P = 0.011). Poor prognosis was found in patients with pCR and a post-nCRT SUVmax ≥3 as compared with those with pathological partial response and a post-nCRT SUVmax &lt;3.
SUVmax ≥3 is a poor prognostic factor in ESCC after trimodality treatment, even in patients with pCR.
256. LOCAL CONTROL OF HEPATIC/PULMONARY OLIGOMETASTASIS IS EFFECTIVE IN EGJ ADENOCARCINOMA
Authors: Imamura Yu , Kanie Yasukazu , Maruyama Suguru , Sakamoto Kei , Kuriyama Kengo , Okamura Akihiko , Kanamori Jun , Watanabe Masayuki 
Published: September 2022

Abstract
This study investigated the clinicopathological features of distant metastasis of esophagogastric junction (EGJ) adenocarcinoma. Survival benefit of local management was also examined in the patients with hepatic or pulmonary oligometastasis.
Among a total of 449 cases of Siewert type I-II surgically resected EGJ adenocarcinoma (2005–2020), 166 cases with distant metastasis were eligible.
Examining 22 cases with liver metastasis alone who treated in our hospital, liver-resected cases (N = 13) experienced better outcomes (mOS; 48 M for resection, vs. 8.1 M for those without resection, P = 0.0002). More favorable outcome was observed in the patients with 1–3 nodules (N = 11, P = 0.0023). Regarding lung metastasis alone, systemic chemotherapy was applied to bilateral multiple nodules, otherwise, local control including resection or stereotactic irradiation was selected. The mOS in the patients who underwent local control was significantly longer than that of chemotherapy (44 M for resection vs. 17 M for chemotherapy, P = 0.035).
Tumor location or histological type of the primary tumor was associated with organ sites of distant metastasis. Local management conferred survival benefit in the patients with oligometastasis in liver or lung alone.
258. OUR PROCEDURE OF RECONSTRUCTION DURING ESOPHAGEAL SURGERY
Authors: Tanaka Yoshihiro , Sato Yuta , Ohno Shinya , Asai Ryuichi , Endo Masahide 
Published: September 2022

Abstract
The incidence of anastomotic leakage in esophagectomy and reconstruction surgery is reported over 10%. We have used subtotal stomach (SS) for reconstruction.
We retrospectively examined the results of SS reconstruction, postoperative weight changes, and quality of life. We have used SNS to deal with postoperative dietary problems. We also have devised a method for combined oral nutritional supplementation by the conceot of ‘Taking a ONS along with the meal by knowing appetite: Tanaka Method.
400 cases. Anastomotic leakage was found in 2 cases (0.50%). Many cases of early feeling of fullness were observed at 3 months. The patients’ body weights, median [interquartile range], were as follows: pretreatment, 54.1 [48.9,59.9] Kg: 12 months postoperatively, 52.75[47.5–59.15] Kg: 36 months postoperatively, 52.55[47.35–59.2] Kg: 60 months postoperatively, 51.2 [46.25,58.45] Kg.
SS reconstruction seems to be feasible.
261. MALNUTRITION DEFINED BY GLIM CRITERIA ASSOCIATES WITH INCREASED RISK OF ADVERSE OUTCOME AFTER OESOPHAGO-GASTRIC CANCER SURGERY
Authors: Murnane Lisa , Adrienne Forsyth , Koukounaras Jim , Kalai Shaw , Wendy Brown , Audrey Tierney , Burton Paul 
Published: September 2022

Abstract
Low muscle mass is associated with postoperative complications after oesophago-gastric (OG) cancer surgery, but data demonstrating a negative impact on long-term survival is limited. Clinical tools to accurately stratify risk based on nutritional status would be of considerable value. The Global Leadership Initiative on Malnutrition (GLIM) is a consensus framework for diagnosing malnutrition. We aimed to assess the prevalence of malnutrition defined by GLIM and the impact on postoperative outcomes after OG cancer surgery.
Patients who underwent radical OG cancer surgery with preoperative abdominal computed tomography (CT) imaging were included. Retrospective collection of preoperative data identified malnutrition using the GLIM definition. The phenotypic criterion includes body mass index (BMI), unintentional weight loss, and muscle mass. All patients had a malignant disease and met the aetiologic criterion of an inflammatory condition. Nutrition status was categorised as no malnutrition, mild–moderate, and severe. Malnutrition diagnosis was assessed against oncological, surgical, and survival data. Low skeletal muscle index (cm2/m2) measured by CT was determined using predefined cut-points.1 Cox regression analysis determined predictors of overall survival.
One-hundred and eight patients were included. Malnutrition using GLIM criteria was present in 72% of patients (n = 78), including mild–moderate (n = 45) and severe malnutrition (n = 33). The predominant phenotypic criterion for GLIM malnutrition was low muscle mass (n = 66, 61%), followed by preoperative weight loss (n = 46, 43%) and low BMI (n = 11, 10%). Malnutrition was associated with postoperative pneumonia (26.9% vs 6.7% well-nourished, p = 0.010). Severe malnutrition was associated with poorer 5-year overall survival (p = 0.022) (Figure 1) and, along with stage 4 disease, higher age, and severe postoperative complications, remained an independent predictor of survival after multivariate analysis (OR 2.51, 95% CI 1.20–5.24, p = 0.014).
Malnutrition defined by GLIM is highly prevalent and is associated with postoperative pneumonia. Severe malnutrition is an independent predictor of poorer overall survival. Muscle mass is a key phenotypic GLIM criterion, and the GLIM diagnostic framework is potentially a practical and valuable component of preoperative risk stratification in OG cancer surgery.
265. SIGNIFICANCE OF AGR2 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Konishi Hirotaka , Takabatake Kazuya , Kataoka Satoshi , Shibamoto Jun , Furuke Hirotaka , Shiozaki Atsushi , Fujiwara Hitoshi , Otsuji Eigo 
Published: September 2022

Abstract
Anterior gradient 2 (AGR2) promotes tumor growth and make a worse prognosis in several cancers, especially in adenocarcinoma. However, comprehensive functional analysis of AGR2 in esophageal squamous cell carcinoma (ESCC) has not been reported.
In the present study, the functional analysis and clinical significance of AGR2 were examined using ESCC cell lines and clinical samples.
AGR2 was upregulated in ESCC cell lines and ESCC tissue sample. The downregulation of AGR2 suppressed cell proliferation and increased the proportion of G2/M-phase cells. Furthermore, phosphorylation of p53 in TP53-wild-type ESCC and osteosarcoma cells was also promoted. However, these changes were not observed in TP53-mutant ESCC cells. Immunohistochemistry results showed that high AGR2 and low p53 expression in ESCC tissue was correlated with a worse prognosis. These results suggest that although AGR2 enhances cell proliferation by inhibiting p53 phosphorylation in TP53-wild-type ESCC, the same mechanism does not regulate cell functions in TP53-mutant ESCC due to suppression of TP-53 function.
In conclusion, AGR2 plays an important role in ESCC progression and might be a useful prognostic marker in patients with TP53-wild-type ESCC.