bluuebunny/crossref_metadata_2025 huggingface dataset:
152. CLINICAL OUTCOME OF NIVOLUMAB COMBINATION THERAPY AS 1ST LINE TREATMENT FOR ESOPHAGEAL CANCER IN A JAPANESE HOSPITAL (CHECKMATE 648)
Authors: Makino Tomoki , Tanaka Koji , Yamashita Kotaro , Eguchi Hidetoshi , Doki Yuchiro
Published: September 2022

Currently, immuno-checkpoint inhibitor (ICI) has been widely used for unresectable advanced/recurrent esophageal squamous cell carcinoma (ESCC) as 2nd or later line treatment, however clinical evidence regarding efficacy or safety of the 1st line ICI treatment for ESCC remains limited. The global phase 3 CheckMate 648 (ONO-4538-50) demonstrated significant overall survival (OS) benefit of nivolumab + chemotherapy and nivolumab+ ipilimumab versus chemotherapy (5FU/CDDP) in previously untreated patients with advanced ESCC with an acceptable safety profile.

A total 970 ESCC patients with unresectable advanced/recurrent disease were randomized globally and this post-hoc exploratory subgroup analysis presented here includes only the 34 patients randomized and treated at this hospital during Dec, 2017-Dec, 2019. Treatment efficacy and adverse events were assessed among the three groups; nivolumab (3 mg/kg every 2 weeks) + ipilimumab (1 mg/kg every 6 weeks) (Group A, n = 11), nivolumab (240 mg every 2 weeks) + 5FU/CDDP (5FU800 mg/m2 day1–5/CDDP80 mg/m2 day 1、every 4 weeks) (Group B, n = 13) and 5FU/CDDP (5FU800 mg/m2 day1–5/CDDP80 mg/m2 day 1、every 4 weeks) (Group C, n = 10).

Patient characteristics of the group A/B/C were as follows; age = 69 (52–82)/70 (52–85)/70 (55–75), gender (male/female) = 11:0/10:3/9:1. Regarding survival analysis (median follow-up time; 19.5 months) of Jan 24th, 2022, median OS were not reached in the group A, 15 months (95%CI = 5–28) in the group B and 12 (95%CI = 2–25) months in the group C. The most common treatment-related adverse events (≥ grade3) were pruritus in 2 cases, rash in 2 (Group A), neutropenia in 5 cases, leukopenia in 3, and anorexia in 3 (Group B) and no cases (Group C). No treatment-related death was identified in any groups.

The results from this Japanese single-center exploratory subgroup analysis are consistent with the global study results, and support nivolumab + ipilimumab and nivolumab + chemotherapy as promising first-line treatments for patients with unresectable advanced/recurrent ESCC. Also, establishment of useful biomarker in distinguishing use of nivolumab + chemotherapy and nivolumab+ ipilimumab would be urgent.
153. APPLICATION OF RAMAN SPECTROSCOPY AND MACHINE LEARNING IN THE CLASSIFICATION OF ESOPHAGEAL SQUAMOUS CARCINOMA
Authors: Chen Long-Qi , Huang Wenhua
Published: September 2022

Esophageal squamous cell carcinoma (ESCC) is a common disease among all malignant tumors. Advanced detect technologies of the esophageal cancer, Raman spectroscopy have then been developed with the aim of improving diagnosis sensitivity and specificity and accuracy. The aim of this study was to demonstrate an effective and noninvasive technique, Raman spectroscopy, which was able to differentiate and classify ESCC cell lines (esophageal cancer tissue types).

5 ESCC cell lines and tissues of ESCC patient with staging of T3N1M0 (n = 4) and T3N2M0 (n = 4) in low and high differentiation were examined through Raman spectroscopy. Raman spectra data analysis with four machine learning algorithms: PCA-LDA, PCA-XGB, PCA-SVM and PCA- (LDA, XGB, SVM)-stacked GBM were applied. The Student’s t test was used to analyze the differences between the two groups.

PCA-LDA model achieved predictive sensitivity greater than 89%, specificity greater than 96% and the overall accuracy rate greater than 90% for the classification of ESCC cells. PCA-XGM and PCA-SVM models showed overall predictive accuracies of 85% and 87.7%, respectively. The overall accuracy reached to 94.7% in classifying the ESCC cells and normal esophageal cells. In ESCC tissue, Raman intensity of DNA/RNA (780 cm − 1) and lipids (1440 cm − 1) were higher in ESCC tissues compared with that in adjacent tissues. We used PCA-XGB model to classify ESCC tissues and adjacent tissues, which showed the overall predictive accuracy of 85%.

This study illustrates Raman spectral traits of ESCC cell lines and esophageal tissues related to clinical pathological diagnosis, and one more possible detection method has been added in the field of esophageal cancer detection. Future studies to determine the role of different Raman spectral features altered in ESCC pathogenesis are warranted.
155. CAN ANAEROBIC THRESHOLD (AT) PREDICT LENGTH OF STAY IN PATIENTS UNDERGOING IVOR LEWIS OESOPHAGECTOMY
Authors: Joel Abraham , Samuel Maria , Quake Sharmaine , Bailey Haydn , Zeyuan Chew , Ahmed Salman , Viswanath YKS , Dresner Samuel , Davis Peter
Published: September 2022

Variables from cardiopulmonary exercise testing (CPET) has been used to predict negative prognostic markers in oesophagectomy. We investigate the predictive value of anaerobic threshold (AT) ≥11 mL/kg/min in predicting length of stay (LOS) in patients having Ivor Lewis oesophagectomy (ILO). We also correlate AT with pulmonary complications (pneumonia), anastomotic leak rate and survival in our outcome analysis.

A retrospective analysis of a prospectively maintained database was carried out at a regional centre in the UK, evaluating patients undergoing ILO for oesophageal cancer (OC) between May 2016 and December 2019. Data was collected using the hospitals electronic system containing clinic letters, anaesthetic assessment including CPET, pathology reports and information regarding death of the patient. Patients were divided into AT <11 mg/kg/min (LAT) and those with AT ≥11 mg/kg/min (HAT). χ2 test of association were used for categorical variables and Mann–Whitney test to compare two sets of non-parametric data. A p < 0.05 was considered significant. Kaplan–Meier curve was used for survival analysis.

153 patients underwent ILO (median age 67, 86% males). 70 from this cohort underwent CPET testing. Median AT was 10.5 (7.4–11.7). There was a statistically significant negative correlation between AT and LOS (p = 0.03). Median LOS for patients with LAT was 15.5 days (11–225) and HAT was 13.5 days (10–19.75) with no significant differences in LOS when comparing LOS between LAT and HAT (p = 0.09). There was no difference in anastomotic leaks between LAT and HAT (χ2 test) (p = 0.15). Overall survival estimated using Kaplan–Meier curves failed to demonstrate a statistical difference between LAT and HAT (median 28.5 vs 30.5) (p = 0.71).

Our analysis shows a negative correlation between AT and LOS. Although LOS, anastomotic leaks, and survival were quantitatively better in the HAT group, it failed to reach statistical significance. This suggests that CPET variables are more beneficial as adjuncts to help shared decision making but not to predict post-operative outcomes. AT does not predict LOS in patients undergoing ILO.
159. NEW ENDOSCOPIC TREATMENT TECHNIQUE TO PREVENT REFRACTORY CORROSIVE ESOPHAGEAL STRICTURES
Authors: Tharavej Chadin , Chobarporn Thitiporn
Published: September 2022

Refractory esophageal stricture is an undesired complication after caustic ingestion associated with increased morbidity and mortality. Prevention rather than treatment of the stricture is a desirable goal. The objective of this study was to report the safety and outcome of our novel endoscopic technique using Repeated endoscopy with Intraluminal Fibrinous adhesioLysis of the Esophagus (RIFLE) during the first 2 weeks of caustic ingestion aiming to prevent the development of refractory esophageal stricture and bypass surgery.

Patients with Zagar’s grade IIb-IIIa corrosive esophageal injury were included. Patients undergoing emergent surgery were excluded. Since 2018, upper endoscopy with lysis of intraluminal fibrinous adhesion by advancing endoscopic tip through the lesions has been gently performed initially at the third day and then repeated twice a week during the first 2 weeks of the ingestion in 15 patients of the study group. Before 2018, a standard ‘wait and see’ treatment with early dilation at 4–6 weeks after injury had been applied only patients with evidence of esophageal stricture. Patients in the standard were 1:1 matched to the study group.

A median number of endoscopic RIFLE session was 4, and there was no treatment-related complication in all 15 patients in the study group. Fifteen out of the 102 patients with grade IIb-IIIa esophageal injury in our database with standard treatment were well matched to the study group. At the median follow-up of 30 months, the frequency of esophageal stricture, refractory esophageal stricture, esophageal replacement procedure, and a median number of dilation session between the study and standard treatment group were 4/15 (27%) vs 10/15 (67%), p = 0.02, 1/15(7%) vs 7/15(47%), p = 0.01, 1/15(7%) vs 6/15(40%), p = 0.03, and 4 vs 11, p < 0.001, respectively.

In patients with severe non-transmural caustic esophageal injury, repeated endoscopy with intraluminal fibrinous adhesiolysis of the esophagus during the first 2 weeks of the ingestion is safe and associated with decreasing proportion of patients with refractory esophageal stricture and requiring esophageal replacement procedure.
166. A STUDY OF THE LEARNING CURVE FOR LAPAROSCOPIC-ASSISTED SINGLE-PORT MEDIASTINOSCOPIC ESOPHAGECTOMY
Authors: Cao Qingdong , Wu Xiangwen , Li Wenhao , Gan Xiangfeng
Published: September 2022

Laparoscopic-assisted single-port mediastinoscopic esophagectomy is a safe and effective emerging minimally invasive esophagectomy. However, nothing has been reported about the learning curve for this technique. The goal of this study was to analyze the learning curve of this technique and to determine the number of procedures performed to achieve different levels of proficiency to improve surgeons’ understanding of the learning process of this new technique.

This study retrospectively collected clinical data on consecutive laparoscopic-assisted single-port mediastinoscopic esophagectomies performed by the same surgeon at our center from October 2016 to August 2021. A simple scatter plot of the number of procedures versus procedure time and its trend line were plotted, using procedure time as an indicator of efficiency. Learning curves were quantitatively assessed by unadjusted cumulative sum values using the cumulative summation method, different segments were derived using joint point linear regression analysis, and variables were compared between subgroups using trend analysis. The survival analysis was performed using the Kaplan–Meier method.

The learning curve could be divided into 3 different stages: the 1st–91st, 91st-125th, and 125th-182nd procedures comprised the preliminary, transition, and proficient stages, respectively. Compared with the preliminary stage, the procedure time, bleeding volume, postoperative hospital stays, and the incidence of anastomotic fistula were significantly lower in the proficiency stage, whereas the number of harvested lymph nodes and the rate of recurrent laryngeal nerve lymph node harvest was significantly higher. Additionally, there were no significant differences in overall survival and disease-free survival at different stages for patients with all, different T stages, and different N stages within 1 year postoperatively.

In this study, there may be 3 stages of varying proficiency in the learning curve of laparoscopic-assisted single-port mediastinoscopic esophagectomy. Approximately 91 consecutive procedures were required to overcome the preliminary stage, whereas proficiency in this technique required approximately 125 consecutive procedures. Moreover, as the learning curve reached the proficiency stage, the perioperative indicators tended to stabilize. Furthermore, the short-term survival of patients might not be influenced by technical proficiency.
167. LYMPHATIC INVASION CAN PREDICT POSTOPERATIVE LYMPH NODE RECURRENCE IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Ma Yu , Wang Hongtao , Zhu Jianfei
Published: September 2022

Lymph node metastasis is an important pathological feature of esophageal squamous cell carcinoma (ESCC), and previous studies have confirmed that patients with lymphatic invasion (LI) have poor prognosis. However, the correlation between LI and pathological N stage and its impact on patient prognosis are less studied.

Patients with ESCC who underwent radical esophagectomy in our center were included in a retrospective analysis, and LI was assessed using hematoxylin and eosin (H&E) staining and D2–40 immunohistochemistry (IHC). Correlations between PI and clinicopathological features and clinical outcomes were also analyzed.

Totally, LI presented in ESCC were 22.5% (86 of 383). LI was closely related to the pN stage, with the pN stage from N0 to N1, then to N2, and finally to N3, the incidence of LI gradually increased from 1% to 40%. Furthermore, PNI-positive patients had poorer disease-free survival (DFS) than PNI-negative patients (21.0 months vs 41.4 months, P < 0.001), the same result was obtained in OS (26.4 months vs 56.4 months, P < 0.001). Finally, the probability of postoperative lymph node recurrence in LI-positive patients was significantly higher than that in LI-negative patients (20.9% vs 18.5%, P = 0.026).

LI is related to pN stage of ESCC patients. It is also an important predictor of postoperative lymph node recurrence in patients with ESCC.
173. POSTOPERATIVE CHEMORADIATION FOR LOCAL ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA WITH LOW MEAN PLATELET VOLUME
Authors: Wang Qifeng , Wu Lei , Zhu Jie , Ni Wenjie , Chang Xiao , Xiao Zefen , Han Yongtao
Published: September 2022

To develop mean platelet volume (MPV) as a biomarker to predict prognosis and guide postoperative chemoradiation (POCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).

We proposed a blood biomarker, MPV, for predicting disease-free survival (DFS) and overall survival (OS) in LA-ESCC patients who underwent surgery (S) alone or S + POCRT. The median cut-off value of MPV was 11.4 fl. We further evaluated whether MPV could guide POCRT in the study and external validation groups. We used multivariable Cox proportional hazard regression analysis, Kaplan–Meier curves, and log-rank tests to ensure the robustness of our findings.

In the develop group, MVP was associated with OS and DFS defined by clinicopathological variables and remained an independent prognostic factor in the multivariate analysis (p = 0.001 and p = 0.002, respectively). For high MVP, 5-year OS and DFS were significantly improved compared to those with low MPV (p = 0.0011 and p = 0.0018, respectively). Subgroup analysis revealed that POCRT was associated with improved 5-year OS and DFS compared with S alone in the low-MVP group (p < 0.0001 and p = 0.0002, respectively). External validation group analysis (n = 112) showed that POCRT significantly increased 5-year OS and DFS (p = 0.0035 and p = 0.0062, respectively) in patients with low MPV.

MPV as a novel biomarker can improve prognostic prediction and help identify patients most likely to benefit from POCRT for LA-ESCC.
178. NEOADJUVANT CHEMORADIOTHERAPY VERSUS CHEMOTHERAPY FOR GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA; WHICH IS THE OPTIMAL TREATMENT OPTION?
Authors: Farinha Hugo Teixeira , Zandirad Eric , Barberà-Carbonell Beatriz , Demartines Nicolas , Schäfer Markus , Mantziari Styliani
Published: September 2022

Patients with locally advanced gastroesophageal junction (GEJ) adenocarcinoma are treated either with either perioperative chemotherapy (CT) or preoperative radiochemotherapy (RCT) followed by surgery. However, specific selection criteria of one modality over the other still lack, as comparative data for their efficacy remain scarce. The aim of this study was to compare pathologic response and long-term outcomes in GEJ adenocarcinoma patients treated with neoadjuvant RCT versus CT.

All patients with locally advanced GEJ adenocarcinoma treated with neoadjuvant treatment (NAT) followed by surgery between 2009 and 2018 in our tertiary referral center were retrospectively analyzed. The x2 or Fisher test were used to compare categorical, and the Mann–Whitney-U test continuous variables. Survival and tumor recurrence were compared with the Kaplan Meier method and log-rank test. Multivariate logistic and Cox regression were performed to identify independent predictors of complete pathological response and long-term survival.

Among the 94 included patients, 67 (71.2%) received RCT and 27 CT. Complete pathologic response was more frequent in RCT patients (13.4% vs 7.4%, p = 0.009), who had a trend to better lymph node control (ypN0) (55.2% vs 33.3%; p = 0.057), but similar rates of R0 resection (66.7% vs 72.1% CT, p = 0.628). RCT patients had more postoperative cardiovascular complications (35.8% vs 11.1%; p = 0.017). Long-term overall and disease-free survival were similar in the two groups (5-year OS 61.1% RCT vs 75.7% CT, p = 0.259; 5-year DFS 33.5% RCT vs 22.8% CT; p = 0.763). NAT type was not independently associated with pathologic response nor long-term survival.

Patients with locally advanced GEJ adenocarcinoma demonstrated higher rates of complete pathologic response after neoadjuvant RCT than CT and a trend to superior locoregional lymph node sterilization, although this did not translate in a significant survival or recurrence benefit.
184. THE PROGNOSTIC VALUE AND MOLECULAR PROPERTIES OF TERTIARY LYMPHOID STRUCTURES IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Wen Jing , Ling Yihong , Zhong Jian , Weng Zelin , Lin Guangrong
Published: September 2022

Tertiary lymphoid structures (TLSs) play key roles in tumor adaptive immunity. However, the prognostic value and molecular properties of TLSs in esophageal squamous cell carcinoma (ESCC) patients have not been studied.

The prognostic values of the presence and maturation status of tumor-associated TLSs were determined in 394 and 256 ESCCs with hematoxylin and eosin (H&E)-stained slides from Sun Yat-sen University Cancer Center (SYSUCC) and Cancer Hospital of Shantou University Medical College (SUMCCH), respectively. A deep-learning TLS classifier was established with H&E-stained slides using inception-resnet-v2 neural network. Digital spatial profiling (DSP) was performed to determine the cellular and molecular characteristics of TLSs in ESCCs.

Immature and mature TLSs were observed in 30.2% and 42.9% ESCCs from SYSUCC by pathological examination. The deep-learning TLSs classifier yielded an area under curve value of 0.975 for patients’ mature TLS detection in the external test set, by which 55.1% ESCCs from SUMCCH were identified with mature TLSs. The presence of mature TLSs associated with an earlier pT-stage and improved survival. Mature TLSs were characterized by increased proportions of proliferating B, plasma, and CD4+ Th cells, and increased B memory, CD4+ T activated and effector memory, and Th17 signatures. TLS-mature ESCCs were with increased intratumoral CD8+ T infiltration.

Mature TLSs provide a privileged microniche for B and T cell differentiation and maturation, thereby generating an effective anti-tumor humoral and cellular immunity to improve ESCC prognosis.
187. ADENOCARCINOMA OF DISTAL ESOPHAGUS AND ESOPHAGO-GASTRIC JUNCTION: CROSS VERSUS FLOT PROPENSITY SCORE MATCHING ANALYSIS OF SURVIVAL IN A SINGLE-CENTER INSTITUTION
Authors: Lombardi Pietro Maria , Marano Salvatore , Basato Silvia , Pansa Andrea , Giorgi Lorenzo , Perano Vittoria , Castoro Carlo
Published: September 2022

Multimodal treatments are the gold standard for advanced resectable gastroesophageal cancer. The exclusive neoadjuvant, chemoradiation-based CROSS regimen and the perioperative chemotherapy-based FLOT regimen are commonly adopted for adenocarcinoma of distal esophagus and esophago-gastric junction (EGJ). At present, there is no clear evidence of the superiority of either of these two approaches on survival.

An intention-to-treat analysis was performed on a cohort of consecutive patients who underwent neoadjuvant CROSS or FLOT regimen and subsequently confirmed to curative-intent surgery for adenocarcinoma of distal oesophagus and EGJ between August 2017 and October 2021. Propensity Score Matching (PSM) was performed in order to balance baseline characteristics of patients undergoing CROSS and FLOT neoadjuvant regimen. The primary endpoint was Overall Survival (OS). Secondary endpoints included Disease-Free Survival (DFS), 90-day morbidity rate, margin status, incidence and pattern of recurrence. Subgroup analyses were performed according to the specific neoadjuvant regimen adopted.

Of the 111 patients included, 84 were correctly matched after PSM, 42 in each group. CROSS and FLOT patients showed similar 1-year OS rate (85.3% and 85.4% respectively, p = 0.189) and 1-year DFS rate (73.3% and 81.3% respectively, p = 0.267). When compared to FLOT patients, CROSS patients reported lower but not significant rates of post-operative severe complications (4.8% vs 11.9%, p = 0.433) and negative margins of resection (95.2% vs 97.6%, p = 1.000). In the CROSS group, 89% of recurrences occurred outside the radiation field. In FLOT group, 69% of patients completed all the 8 expected perioperative cycles.

FLOT and CROSS offer similar OS and DFS, together with comparable 90-day morbidity/mortality rates and pathological findings. Both regimens are affected by specific limitations that have to be kept in mind during treatment assessment. The results of ongoing Randomized Controlled Trials are urgently awaited.
200. SAFETY AND EFFICACY OF CONVERSION SURGERY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Tsuji Takayuki
Published: September 2022

Recently, cases of conversion surgery for unresectable esophageal cancer are increasing. Last year, in Japan, Cisplatin +5-FU (CF) + Pembrolizumab is recommended as 1st line therapy for unresectable esophageal squamous cell carcinoma (ESCC), based on the results of the KEYNOTE 590 trial. With improvement of response rate, conversion surgery is expected to become a main option for treatment strategy for unresectable ESCC.

【Methods】<100.

In our institute, conversion surgery is considered for patients with para-aortic lymph node-positive advanced ESCC who have no other distant metastases, if the para-aortic lymph node metastases have disappeared after systemic chemotherapy. There were 30 patients of unresectable esophageal cancer with positive para-aortic lymph node metastasis from 2011 to 2020. Seven of these patients showed disappearance of para-aortic lymph node metastasis and underwent conversion surgery. Characteristics, short-term and long-term results of these seven cases are studied.

All of the seven patients who had para-aortic lymph node metastases were treated with induction DCF (Docetaxel + CF) as initial treatment. After disappearance of para-aortic lymph node metastases, thoracoscopic or open esophagectomy was performed. Four patients (57%) had Clavien-Dindo grade 2 or 3 complications, but no perioperative death was observed. Three patients (43%) had recurrence, within mediastinum lymph node, abdominal lymph node or adrenal gland. 3-year DFS was 57% and 3-year OS was 83%.

Conversion surgery is safe and feasible in cases that responded to systemic chemotherapy. Some cases showed good prognosis. Long-term survival is expected with conversion surgery.
201. PREDICTION OF LYMPH NODE METASTASIS IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA USING GENETIC SIGNATURES FROM LARGE-SCALE GENOMIC REPERTOIRES
Authors: Kang Xiaozheng , Wan Zhiyi , Zhang Ruixiang , Zhang Enli , Zhao Yahui , Qi Shu , Chen Xiankai , Qin Jianjun , Li Yin
Published: September 2022

The presence of lymph node metastasis puts patients with resectable esophageal squamous cell carcinoma (ESCC) at a high risk of disease recurrence, and these patients would benefit from neoadjuvant treatment. However, current clinical staging is not enough to capture all patients with high-risk disease, and novel diagnostic tools are required to improve the accuracy of treatment planning. We tried to explore a better prediction using genomic features from large-scale gene mutation data.

The major public data repositories of whole-exome sequencing for ESCC were involved in this study. The absolute differences in gene mutation frequency were calculated using Fisher’s exact test in nodal negative versus nodal positive patients. The classification of gene mutation status was dichotomized as wild-type and mutant type. To find a reliable gene panel that could provide sufficient population coverage, we set the cut-off level above 85% in both nodal phenotypes. The genomic classifier for nodal metastasis risk prediction was further generated by LASSO logistic regression analysis with 10-fold cross-validation based on the topmost significantly different genes.

Above the threshold values, a total of 120 differentially mutated genes were identified in the 561 ESCC genomic sequencing data. The population coverage rates were 85.97% in the nodal positive group (n = 335) and 88.05% in the nodal negative group (n = 226), respectively. According to the LASSO logistic regression approach, a panel of 112 topmost relevant genes (termed LNM112) was selected. The receiver operating characteristic curve of the LNM112 predictive model was plotted with an area under the curve value of 0.95 (95% CI: 0.93–0.96). The sensitivity and specificity of the LNM112 model were 96.72% (324/335) and 71.24% (161/226), respectively.

We identified a genomic signature (112 genes) from the large-scale genomic repertoires capable of predicting lymph node metastasis in ESCC. It can be incorporated into the current staging modalities to help inform treatment decisions, and external validation is warranted in different populations.
205. PREDICTORS OF THE DIFFICULTY OF TRANSCERVICAL SUBCARINAL LYMPH NODE DISSECTION IN ESOPHAGEAL CANCER
Authors: Furuke Hirotaka , Fujiwara Hitoshi , Konishi Hirotaka , Shiozaki Atsushi , Ohashi Takuma , Shimizu Hiroki , Arita Tomohiro , Yamamoto Yusuke , Morimura Ryo , Ikoma Hisashi , Kuriu Yoshiaki , Kubota Takeshi , Okamoto Kazuma , Otsuji Eigo
Published: September 2022

Transmediastinal radical esophagectomy (TME) is a new minimally invasive approach without thoracotomy. However, transcervical dissection of subcarinal lymph nodes (SCLN) is challenging. The shape or narrowness of the mediastinal space, especially around the aortic arch to tracheal bifurcation, may affect the difficulty. The present study aimed to clarify predictors for the difficulty of transcervical SCLN dissection.

Patients who underwent TME between 2016 and 2019 were included (n = 126). Four indicators, the cervical angle, carina distance, aorta distance, and sternum distance, were defined as indicators of the mediastinal narrowness by 3D-CT. The relationship between the difficulty of the transcervical SCLN dissection and clinicopathological features, including the above indicators, were investigated.

In a univariate analysis, the cervical angle (p = 0.023), aorta distance (p = 0.002), and middle thoracic tumor (p = 0.040) correlated with the difficulty. The median cervical angle (degree) and aorta distance (mm) were 15 and 33 in difficult cases, and 19 and 43 in easy cases, respectively. In a multivariate analysis, middle thoracic tumor (odds ratio: 3.28, p = 0.050) and a short aorta distance (odds ratio: 5, p = 0.036) were independent predictive factors.

The cervical angle, aorta distance, and middle thoracic tumor may predict the difficulty of transcervical SCLN dissection. In difficult cases, transhiatal approach is essential for safe lymphadenectomy.
209. THE EFFECT OF ENHANCED RECOVERY AFTER MINIMALLY INVASIVE ESOPHAGECTOMY: A RANDOMIZED CONTROLLED TRIAL
Authors: Shen Yaxing , Wang Hao , Fang Yong , Yin Jun , Tan Lijie
Published: September 2022

The purpose of this randomized controlled trial was to determine if enhanced recovery after surgery (ERAS) would improve outcomes in patients undergoing minimally invasive esophagectomy (MIE) for esophageal cancer.

Patients with esophageal cancer undergoing MIE between March 2016 and August 2018 were enrolled. Patients were randomly divided into 2 groups: ERAS+ group that received a guideline-based ERAS protocol, and ERAS- group that received standard care. The primary endpoint was morbidity after MIE. The secondary endpoints were the length of hospital stay and time to ambulation after the surgery. The perioperative results were also collected and compared.

A total of 60 patients in the ERAS+ group and 58 patients in the ERAS- group were included. Demographic and clinical features were similar between the groups. Postoperatively, the overall morbidity rate was lower in the ERAS+ group (33.3% vs. 51.7%; p = 0.04), as was the pulmonary complication rate (16.7% vs. 32.8%; p = 0.04). The ERAS+ group began ambulation at a mean of 2.8 days, as compared to 3.3 days for the ERAS- group (P = 0.001). The length of hospital stay was similar between the groups (9 days vs. 9 days; p = 0.70).

Implementation of an ERAS protocol for patients undergoing MIE resulted in earlier ambulation and lower complications, without a further change in overall length of hospital stay.
217. LAPAROSCOPIC FUNDOPLICATION EFFECTIVE IN TREATING REFLUX MICRO-ASPIRATION
Authors: Khoma Oleksandr , Van der Wall Hans , Falk Gregory L
Published: September 2022

Pulmonary micro-aspiration has become increasingly recognised subtype of severe gastro-oesophageal reflux disease (GORD). Acid suppression can help with symptoms in proportion of patients, however, does not reduce pulmonary contamination with gastric content. Laparoscopic fundoplication was found to be effective in reducing rates of reflux micro-aspiration.

The aim of this study was to examine outcomes of surgical treatment of GORD in patients with confirmed reflux micro-aspiration on novel reflux scintigraphy.

Data was extracted from prospectively populated single centre database. Patients with confirmed reflux aspiration by validated novel protocol scintigraphy and treated with laparoscopic 360-degree Nissen fundoplication between 2006–2018 were included. Primary outcome was resolution of reflux micro-aspiration on post-operative scintigraphy. Secondary outcomes included manometry and scintigraphy findings associated with ongoing aspiration, surgical complications, and patient-reported quality of life outcomes.

Inclusion criteria were met by 159 patients (66% female); average age 58 (SD 14, range 18–88). Most common presenting symptoms were regurgitation and cough.

Laparoscopic fundoplication was associated with resolution of reflux micro-aspiration in 138 (86.8%) of patients. Strongest predictors of persistent aspiration following surgery were severe ineffective oesophageal motility (p = 0.001) and reduced oesophageal clearance (p = 0.003).

Complications (Clavien-Dindo grade III and above) occurred in 4 patients (2.5%). There was no perioperative death in this cohort.

Patient satisfaction rate with surgery was 94%.

Laparoscopic fundoplication is effective in treating reflux micro-aspiration with best outcomes observed in patients with normal oesophageal motility and good oesophageal clearance.
219. DIFFERENT CLINICAL SYMPTOM PATTERNS IN PATIENTS WITH REFLUX MICRO-ASPIRATION CONFIRMED BY NEW PULMONARY ASPIRATION SCINTIGRAPHY TECHNIQUE
Authors: Khoma Oleksandr , Park Jin-soo , Lee Felix , Van der Wall Hans , Falk Gregory L
Published: September 2022

Little primary reported data exists on presenting symptoms of patients in whom reflux micro-aspiration is confirmed. The aim of this study is to report symptoms and presenting patterns of a large group of patients with confirmed reflux micro-aspiration.

Data was extracted from a prospectively populated database of patients referred to a tertiary centre with severe refractory, or atypical reflux (laryngopharyngeal reflux). Patients with reflux micro-aspiration on new technique scintigraphy were included. A comparator group of patients with proven proximal reflux to the level of pharynx when supine and/or upright was also included.

Inclusion criteria were met by 243 patients with confirmed reflux micro-aspiration (33% males; mean age 59, range 17–88).

Most common symptoms amongst patients with micro-aspiration were regurgitation (72%), cough (67%), heartburn (66%), throat clearing (65%), and dysphonia (53%). The most common two-symptom combinations were heartburn/regurgitation, cough/throat clearing, regurgitation/throat clearing, cough/regurgitation and dysphonia/throat clearing. The most common three-symptom combinations were cough/heartburn/regurgitation, cough/regurgitation/throat clearing and dysphonia/regurgitation/throat clearing.

Cluster analysis demonstrated two main symptom groupings, one suggestive of proximal volume reflux symptoms and the other with motility/inflammatory bowel syndrome (IBS)-like symptoms (bloat, constipation).

Combination of typical symptoms of GORD such as heartburn or regurgitation and a respiratory or upper aero-digestive complaint such as cough, throat clearing, or voice change should prompt consideration of reflux micro-aspiration. Atypical reflux symptoms may result from IBS-type abnormality.
223. INTRAOPERATIVE PYLOROPLASTY DURING OESOPHAGECTOMY: A 12 YEAR TERTIARY CENTRE EXPERIENCE
Authors: Chaudhury Madhu , Shetty Vinutha Daya , Ball Chris , Ward Jeremy , Turner Paul , Pursnani Kish , Singh Mohan
Published: September 2022

Delayed gastric emptying (DGE) is a known complication following oesophagectomy with gastric conduit reconstruction. Pyloroplasty is often performed to mitigate the consequences of DGE. It remains contentious whether performing a pyloroplasty has a significant role in reducing DGE. We discuss our twelve-year experience at a single centre routinely performing Heineke-Mikulicz pyloroplasty for all oesophagectomies.

This retrospective study employed an electronic database containing information on all patients who underwent elective Ivor Lewis oesophagectomies from April 2009 to December 2021 in a tertiary upper gastrointestinal cancer centre. Across six surgeons in the centre, a standardised pyloroplasty technique was performed. DGE was defined as patients who had high nasogastric output (> 1.5 litres per day) after ten post-operative days or required endoscopic pyloric balloon dilatation within one year following oesophagectomy.

578 patients underwent Ivor Lewis oesophagectomy during the study period. The mean age was sixty years and the male to female ratio was 1.8:1. The median length of stay was 13 days (3–148). DGE was seen in 9.9% (n = 57) patients. Of these patients, 39.7% (n = 29) cases required oesophageal dilatation within 12 months after their oesophagectomy. 50.8% (n = 21) required in-patient endoscopic dilatation, 14.0% (n = 8) required out-patient endoscopic dilatation. From those who developed DGE, the 30- and 90-day mortality was nil. There were 1.2% (n = 7) leaks specifically from the pyloroplasty which were all managed conservatively.

The rate of delayed gastric emptying is reported to be approximately 15% (Zhang & Zhang, 2018). Our study demonstrates that performing a pyloroplasty reduces this risk to 9.9% and is worthwhile as the complication rate from pyloroplasty is low. Although there are various methods employed in overcoming pyloric sphincter denervation following oesophagectomy (pyloroplasty, pyloromyotomy, digital or instrumental pyloric stretching or intra-operative balloon dilatation), the most effective method of reducing DGE warrants a randomised control trial.
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

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

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

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 < 0.001), circumferential involvement (OR: 5.14, 95% CI: 6.3–17.9; P < 0.001), differentiation (OR 3.65, 2.24–5.93; P < 0.001), lymphovascular invasion (OR 12.18, 95% CI: 5.91–25.21; P < 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

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

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 > station 106recR > station 2 > 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

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.