bluuebunny/crossref_metadata_2025_split huggingface dataset:
556. PREDICTORS OF EARLY RECURRENCE AFTER OESOPHAGECTOMY AND NEOADJUVANT FLOT
Authors: Dayanamby Abbienaya , Chmelo Jakub , Phillips Alexander W 
Published: September 2024

Abstract

Background
FLOT, a novel type of perioperative chemotherapy, has led to improved survival after surgery for oesophageal adenocarcinoma. Yet, rates of cancer recurrence remain high. There is limited research on predictors for early recurrence (ER) in patients receiving FLOT. The aim of this study was to investigate ER and survival rates and identify risk factors of ER.

Methods
Patients who underwent neoadjuvant FLOT and oesophagectomy for oesophageal and oesophagogastric junction adenocarcinomas at a single high-volume centre between August 2018 and January 2023 were evaluated for ER, defined as disease present within one year of surgery. Multivariable logistic regression was conducted to identify risk factors for ER. Patients who died in-hospital or within 90 days of surgery and those with positive longitudinal margin were excluded.

Results
145 patients were included. 139 (95.9%) and 63 (43.4%) patients fully completed neoadjuvant and adjuvant FLOT. 44 patients (30.3%) developed recurrence and 22 patients (15.2%) had ER in the follow up period. Distant, local or mixed type of recurrence was found in 32, 6 and 6 patients respectively. The estimated recurrence free survival and overall survival at one, two and three years were 81.4%, 66.9%, 52.0% and 89.0%, 73.7%, 65.5% respectively. The estimated median survival after recurrence was 4.9 months. In multivariable analysis ypN3 status was identified to be an independent predictor of ER (OR 13.769, 95%CI 1.358-139.573, p=0.026).

Conclusions
This study confirms that ER after neoadjuvant FLOT is common. Patients with a high pathological nodal stage are particularly at risk. It is possible that some patients with ER might have undetected metastases prior to surgery and some do not respond well to neoadjuvant treatment. Identifying chemotherapy non-responders is an important area for future research. These results might be beneficial for prognostication and tailoring follow up care, such as regular surveillance imaging, treatment, and frequency of reviews.
559. SURGICAL PROCEDURE AND CLINICAL OUTCOME OF TRANSMEDIASTINAL ESOPHAGECTOMY FOR ESOPHAGEAL CANCER
Authors: Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hirotaka , Nishibeppu Keiji , Ohashi Takuma , Shimizu Hiroki , Arita Tomohiro , Yamamoto Yusuke , Morimura Ryo , Kuriu Yoshiaki , Ikoma Hisashi , Kubota Takeshi , Otsuji Eigo 
Published: September 2024

Abstract

Background
We started performing esophagectomy by a laparoscopic transhiatal approach in 2009, and 577 patients had undergone to date. Furthermore, we started performing single-port mediastinoscopic cervical approach in 2014, and developed a technique for total mediastinal lymph node dissection (390 patients).

Methods
The upper and middle mediastinal lymph node dissection including lymph nodes along the left recurrent laryngeal nerve, using a left cervical approach, was performed with a single-port mediastinoscopic technique. This approach with pneumomediastinum by AirSeal System improved the visibility and handling in the deep mediastinum around the aortic arch. We recently performed intraoperative monitoring of the recurrent laryngeal nerve using Nerve Integrity Monitor system. For dissection of upper and middle mediastinal lymph nodes, the left recurrent laryngeal nerve was sometimes compressed by the shaft of the sealing device or the retractor. We used continuous monitoring with the Automatic Periodic Stimulation electrode for the left recurrent laryngeal nerve, and immediately recognized dangerous procedures. Frequency of recurrent laryngeal nerve palsy was dramatically reduced to half by the introduction of Nerve Integrity Monitor system. Furthermore, to understand the anatomy of bilateral bronchial arteries, we performed 3-dimensional computed tomography angiography preoperatively, which was crucial to avoid intraoperative bleeding.

Results
The outcome of patients performed transmediastinal radical esophagectomy was compared with those performed the right thoracotomy by using propensity score matching. The operative time, the operative bleeding, and postoperative respiratory complications were significantly decreased by transmediastinal radical esophagectomy.

Conclusion
Our surgical procedure resulted in a good surgical view, safe en-bloc mediastinal lymph node dissection, and the decrease of postoperative respiratory complications.
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563. CURRENT AND PROPOSED TREATMENT STRATEGIES FOR LOCALLY ADVANCED ESOPHAGEAL ADENOCARCINOMA OF THE ESOPHAGOGASTRIC JUNCTION
Authors: Narumiya Kosuke , Kudo Kenji , Toyoshima Yukinori , Ide Hiroko , Osugi Harushi , Okamura Yukiyasu 
Published: September 2024

Abstract

Background
The optimal treatment strategy for locally advanced esophageal adenocarcinoma of the esophagogastric junction (AEG) is still unclear, and no consensus exists whether to treat it as an esophageal cancer or as a gastric cancer, which would include adjuvant therapy. The purpose of this study was to determine the optimal lymph node dissection, considering lymph node metastases and to develop a strategy for treatment that includes adjuvant therapy to improve the survival rate.

Methods
The patients were selected from a retrospective study by the Department of Surgery, Institute of Gastroenterological Surgery, Tokyo Women’s Medical University, that was conducted from 1990 to 2019. We studied 88 cases of advanced AEG in patients who underwent surgery with lymph node dissection. We retrospectively investigated the patient characteristics, pathological findings, surgical procedures, optimum extent of lymph node dissection, location of metastatic lymph nodes, recurrence pattern, and survival curves.

Results
Positivity for H. pylori was 29.8%. Barrett esophagus was found in 33%. Barrett esophagus was low. The calculated index for each nodal station was in stations 1, 2, 3, 7, 11 and 110 for 3-year survival and in stations 1, 2, 3 and 7 for 5-year survival. The proportion with undifferentiated histological type was high. The surgical approach underwent lower esophagectomy + proximal gastrectomy. Double-tract reconstruction was performed in 45%. Adjuvant (postoperative) chemotherapy was given to 51% patients. Preoperative (neoadjuvant) chemoradiotherapy was 17%. The 5-year overall survival rates were 24%.

Conclusion
We found that the optimal lymph node resection consists of the inferior mediastinum (No. 110), the lesser curvature (Nos. 1, 3, 7), No. 2, and No 11. When esophageal involvement was &gt; 40 mm, we performed esophagectomy including upper thoracic lymph nodes. We were not satisfied with the result of surgical treatment including lymph node dissection alone in advanced AEG. We will recommend nab-paclitaxel combined with radiotherapy for advanced AEG to improve the survival rate.
569. PROGNOSTIC VALUE OF T CELL PHENOTYPES AND PD-L1 EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Toyozumi Takeshi , Hu Jie , Murakami Kentaro , Uesato Masaya , Nakano Akira , Kurata Yoshihiro , Hayano Koichi , Matsumoto Yasunori , Otsuka Ryota , Arasawa Takahiro , Takahishi Yumiko , Matsubara Hisahiro 
Published: September 2024

Abstract

Backgrounds
The tumor microenvironment (TME) is a complex niche for tumor cells and immune cells to survive. Tumor-infiltrating lymphocytes (CD8+ T cells, FoxP3+ Tregs…etc), one of the main components of TME, are key factors in the host-tumor immune response, and the exact immune response in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression of PD-L1 and TILs phenotypes in ESCC, their interactions and clinical significance.

Methods
Surgical specimens from 126 ESCC patients who underwent curative surgery between January 2001 and April 2017. We performed immunophenotyping of CD4, CD8, CD25, FOXP3 and PD-L1 within the tumor using immunohistochemistry and multiple immunofluorescence immunolabeling. PD-L1 was detected to expressed on tumor cells (PD-L1 TC) and tumor-infiltrating immune cells (PD-L1 TIIC), and PD-L1 TC affect biologic behavior. The calculation of overall survival (OS) and recurrence-free survival (RFS) were made using Kaplan-Meier analysis, and Cox regression model was used to analyze the correlation between survival and prognosis.

Results
CD8, FoxP3 and PD-L1 expression were positive in 40 (31.7%), 55 (43.7%) and 35 (27.8%) ESCC patient, respectively. CD8 and FoxP3 positive were associated with prolonged OS (p=0.0028, p=0.0324, respectively) and RFS (p=0.0019, p=0.0628, respectively). The overall survival rate in the PD-L1 positive group was statistically lower than that in the negative group (p=0.0402). Furthermore, the combination of CD8/PD-L1 and CD8/Foxp3 was able to more clearly classify and predict prognostic groups of ESCC. Considering the Treg phenotype, the presence of triple positive cell infiltration with Foxp3, CD4, and CD25 was strongly associated with poor prognosis of ESCC (p=0.0349). Cox proportional hazard model suggested that tumor depth, CD8+ infiltration and PD-L1 expression were significantly correlated with overall survival. CD8+ infiltration and PD-L1 expression were revealed to be independent prognostic factors.

Conclusion
CD8 and PD-L1 expression are independent prognostic and predictive factors for ESCC. And it is necessary to elucidate the immune mechanism comprehensively and thoroughly in the insight of multidimensional, multi-molecular and to provide therapeutic strategies for immunotherapy of ESCC.
572. TECHNICAL DETAIL AND SHORT-TERM OUTCOMES OF ROBOT-ASSISTED CERVICAL ESOPHAGECTOMY (RACE) WITH BILATERAL CERVICAL APPROACH FOR ESOPHAGEAL CANCER
Authors: Fujita Takeo , Fujiwara Naoto , Sato Kazuma , Kajiyama Daisuke , Shigeno Takashi , Daiko Hiroyuki 
Published: September 2024

Abstract

Background
The transcervical mediastinoscopic esophagectomy is a relative new technique that has gradually demonstrated because of its ease of dissection along the organ sheath and its less invasive nature. However, the conventional cervical approach to mediastinoscopy has been reported to have a relatively high rate of recurrent nerve palsy due to interference in the mediastinum caused by the straight forceps.
The robot-assisted transcervical esophagectomy (RACE) approach is novel procedure expected to reduce these interferences and improve maneuverability around the recurrent nerve. In this report, we describe a surgical technique and short-term outcome of RACE.

Methods
In this study, we included 26 RACE cases performed between Feb 2023 to Feb 2024.
Principally, our hospital performs transcervical esophagectomy mainly on patients who are difficult to approach by transthoracic approach due to history of thoracic diseases, etc.
In our department, transcervical esophagectomy is usually performed via a bilateral cervical approach, starting from the right neck and continuing to the left neck, and RACE is performed using the da Vinci Xi via a bilateral cervical approach as well. Recently, we have been shortening the operation time by performing simultaneous cervical and abdominal operations without muscle relaxation using NIM.

Results
Patient background: mean age 74.5, male to female ratio 22:4, cStage I/II/III/IV: 13/3/9/1, NAC: 46.1%, more than 80% had some history of pulmonary disease/systemic history.
All patients underwent RACE via bilateral cervical approach, and no intraoperative complications or thoracoscopic conversion were observed. Postoperative complications (CD Grade≥1) included recurrent nerve palsy in 15.6% and respiratory complications in 7.6%. In addition, the recent operation with simultaneous cervical/abdominal NIM and no muscle relaxant has significantly shortened the average total operative time to 4 hours and 40 minutes.

Conclusion
Robot-assisted Cervical Esophagectomy (RACE) is a relatively safe procedure that offers a natural anatomic approach, fewer respiratory complications, and a significant reduction in operative time due to simultaneous neck and abdominal manipulation. With the advancement of robotics and devices, RACE is expected to become more effective and more widely used in the future.
573. SHORT- AND LONG-TERM RESULTS OF RAMIE IN BORDERLINE CT3 /T4B ESOPHAGEAL CANCER AT INITIAL DIAGNOSIS: COMPARISON WITH CONVENTIONAL MIE
Authors: Fujita Takeo , Fujiwara Naoto , Sato Kazuma , Kajiyama Daisuke , Shigeno Takashi , Daiko Hiroyuki 
Published: September 2024

Abstract

Background
Conversion esophagectomy in patients with locally advanced esophageal cancer, initially deemed unresectable, but which has responded to prior therapy, remains unclear. Recently, the utility of RAMIE for locally advanced esophageal cancer has come under discussion. In this study, we first analyzed the short- and long-term outcomes of RAMIE, then investigated the outcomes of conversion RAMIE in cT3br/T4b patients, and compared them with those of conversion using conventional MIE.

Methods
Between January 2020 and August 2023, thirty-three patients with locally advanced esophageal cancer initially diagnosed as cT3br/T4b, who underwent RAMIE after prior treatment, were analyzed, and short-term and long-term postoperative outcomes were evaluated. Additionally, these 33 patients who underwent RAMIE for cT3br/T4b were compared to 48 patients with initial cT3br/T4b who underwent conventional MIE during the same period.

Results
The mean age of RAMIE patients with cT3br/T4b was 63.2 years, with a male-to-female ratio of 26:7, and a clinical stage III/IV distribution of 12/21. Nearly all patients received preoperative treatment with induction chemotherapy (e.g., induction-DCF) or definitive chemoradiation. Among these patients, three underwent R1 or R2 resection. Surgical complications included pneumonia in 18.1% of cases, recurrent nerve palsy in 12.1% (excluding complicated resection cases), and anastomotic leakage in 7.4%. Regarding long-term survival, the 3-year overall survival (3yOS) was 66.2%, and the 3-year disease-free survival (3yDFS) was 48.7% in patients who underwent RAMIE with initial cT3br/T4b.
In the 48 patients who underwent esophagectomy with conventional MIE after pretreatment with cT4br/T4b status, the 3yOS was 52.7%, and the 3yDFS was 40.3%. These survival results for conventional MIE were lower than those for patients who underwent RAMIE (p=0.02).

Conclusion
The short- and long-term outcomes of RAMIE, including cases of T3br/T4 were described, and they were deemed acceptable. Regarding recurrence, local/regional disease control was considered relatively good.
579. DUPILUMAB IMPROVES ENDOSCOPIC FEATURES OF EOSINOPHILIC OESOPHAGITIS IN CHILDREN WITH EOSINOPHILIC OESOPHAGITIS: 52-WEEK ANALYSIS OF THE EOE KIDS STUDY
Authors: Schlag Christoph , Hirano Ikuo , Schroeder Shauna , Chehade Mirna , Menard-Katcher Calies , Hundal Navneet Virk , Liu Ruiqi , Abdulai Raolat , Maloney Jennifer , Glotfelty Lila , Radin Allen 
Published: September 2024

Abstract

Introduction
Eosinophilic oesophagitis (EoE) is a chronic type 2 inflammatory disease. Dupilumab, a fully human monoclonal antibody that blocks drivers of type 2 inflammation, is approved in the USA for EoE patients aged ≥1 year, weighing ≥15 kg, and in the EU for adult and adolescent EoE patients aged ≥12 years, weighing ≥40 kg. The EoE-Endoscopic Reference Score (EREFS) is a validated tool for assessing oesophageal features of EoE, with subscores for inflammation and remodelling. This study assessed the impact of dupilumab on EREFS in children aged 1–&lt;12 years with active EoE in the phase 3 EoE KIDS trial.

Methods
In Part A, 102 patients (mean [SD] age: 7.1 [3.05] years) were randomised 2:2:1:1 to receive weight-tiered dupilumab higher-exposure (HE) or lower-exposure, or placebo (two groups) for 16 weeks. In Part B, all patients received dupilumab at their preassigned dupilumab regimen for a further 36 weeks. This analysis focused on the dupilumab HE and placebo groups. EREFS were scored centrally by reviewers blinded to both treatment allocation and time point. Absolute change from baseline in EREFS total score (0−18), and EREFS inflammation (0−10) and remodelling (0−8) subscores were assessed at Weeks 16 and 52.

Results
A total of 37 and 34 patients received dupilumab HE and placebo, respectively; baseline mean EREFS scores were similar across treatment groups (6.8 vs 7.3) with EREFS inflammation subscores higher than remodelling subscores (6.0 vs 0.9 in the total population). EREFS total score was significantly reduced at Week 16 with dupilumab HE versus placebo (LS mean difference -3.8 [95% CI: -4.9, -2.6], P&lt;0.0001), with improvement sustained through Week 52 in the dupilumab HE group (figure). Similar improvements were observed for EREFS inflammation subscore. Assessment of changes in remodelling was limited by low prevalence of fibrostenotic features in young children.

Conclusion
Dupilumab HE led to significant improvement in EREFS total score at Week 16 versus placebo, which was sustained through Week 52. Dupilumab HE also improved EREFS inflammation subscore.
582. LOW EXPRESSION OF FRG1 PROMOTES MIGRATION AND INVASION IN ESOPHAGEAL CANCER
Authors: Zeng Ya , Su Xi , Zhou Tongfang , Wang Yunfeng , Jia Jingyi , Gao Jie , Deng Yuezhen , Fu Xiaolong , Cai Xuwei 
Published: September 2024

Abstract

Purpose
Distant metastasis is the primary cause of mortality among patients with esophageal cancer. Although FRG1 is known to play a role in the metastasis of various cancers, its specific function in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. In this study, we aimed to explore the role and potential molecular mechanism of FRG1 in the metastasis of ESCC.

Methods
Whole-exome sequencing was performed in ESCC patients who experienced distant metastasis (DM group) and those without metastasis within two years (non-DM group). Bioinformatics analysis and Immunohistochemistry (IHC) validation were conducted. In vitro, FRG1-overexpressed ESCC cell lines were established with lentivirus and validated by western blots. The wound-healing assay, transwell migration and invasion assay were performed in esophageal cancer cell lines. Additionally, RNA sequencing was conducted in ESCC cells to identify potential pathways involved.

Results
Mutations in FRG1 were more frequently observed in DM group compared to those in non-DM group. IHC revealed that the expression of FRG1 in DM group was significantly lower than non-DM group. In vitro, our results showed that ESCC cells with low FRG1 expression exhibited enhanced migration and invasion capabilities. Conversely, overexpression of FRG1 inhibited migration and invasion in ESCC cells. Mechanistically, RNA sequencing analysis showed a total of 93 differential expression genes between FRG1-overexpressed cells and the negative control. Notably, most differential genes were mainly enriched in the PPAR pathway and tyrosine metabolism pathway.

Conclusion
Our findings suggest that low FRG1 expression in patients may be indicative of rapid distant metastasis. The significant impact of FRG1's abnormal expression on the migration and invasion of ESCC cells highlights its potential as a therapeutic target for treating esophageal squamous cell carcinoma.
586. VALUE OF PEPSIN IN SALIVA TO ASSESS THE POSTOPERATIVE OUTCOME OF PATIENTS WITH GERD
Authors: Weitzendorfer Michael , Wallner Eva Johanna , Rabl Charlotte , Emmanuel Klaus , Koch Oliver Owen 
Published: September 2024

Abstract

Background
The aim of this study was to evaluate the value of salivary pepsin to assess the outcome of surgical treatment of patients with gastroesophageal reflux (GERD).

Methods
Forty-five consecutive patients with GERD despite proton pump inhibitor treatment received laparoscopic anti-reflux surgery (LARS). 24-hour esophageal pH-monitoring (MII-pH) and esophageal manometry (HRM) data were documented preoperatively and at 3-month follow-up. Clinical symptoms were rated with the Gastrointestinal Quality of Life Index (GIQLI) and gastrointestinal symptoms were evaluated by a standardized symptom checklist (SCL), assessing the severity and intensitiy of 14 different symptoms. Simultaneous to MII-pH the collection of 3 saliva samples per patient was performed. Treatment failure was defined as improvement of GIQLI and SCL of &lt; 10 points, despite showing a normal DeMeester score.

Results
At baseline, all patients showed a pathological MII-pH measurement. Furthermore, all patients showed postoperatively a normal DeMeester score (mean 7.10 ± 4.56). Ten patients were defined as treatment failures with a change of pepsin concentration from a mean value of 198.73 ng/mL to 186.00 ng/mL (p&gt;0.05). In patients defined as treatment success, mean pepsin value decreased from 205.83 ng/mL to 85.24 ng/mL (p&lt;0.001).

Conclusion
Salivary pepsin could be a marker for treatment success after LARS. However, larger studies are required to reach firm conclusions.
587. PD-L1 EXPRESSION AND CD8+ TUMOR-INFILTRATING LYMPHOCYTES CHANGES AFTER PREOPERATIVE CHEMORADIOTHERAPY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Kim Hak Jae , Kim Byoung Hyuck , Lee Clinical Fellow Tae Hoon 
Published: September 2024

Abstract

Background
Neoadjuvant chemoradiotherapy (nCRT) has been established as a standard treatment for locally advanced esophageal squamous cell carcinoma (SqCC), but there are still insufficient research advances on the incorporation of immunologic agents. The aim of this study was to explore immune microenvironment changes before and after nCRT.

Methods
A total of 101 patients who underwent nCRT followed by radical surgery for esophageal SqCC in a single institution between 2005 and 2021 were analyzed. Pre-nCRT endoscopic biopsy and post-nCRT surgical specimen were evaluated using tissue microarray. Immunohistochemical staining for CD3, CD8, and PD-L1 were performed. Tumor-infiltrating lymphocytes (TIL) density were independently evaluated by blinded pathologist (total number of 2+ to 3+ cells/total area (mm2)).

Results
Compared to pre-nCRT biopsy, PD-L1 expression (8.7% vs. 14.0%, p&lt;0.001) and TIL density (259.1 vs. 566.9, p&lt;0.001) were significantly increased in surgical specimen after nCRT. When divided into groups according to nCRT response, post-nCRT TIL density (p=0.341), fold changes of TIL density (p=0.749), and PD-L1 expression (p=0.642) were not significantly different between ypCR (n=23) and non-ypCR group (n=78). In ypT0 group (n=36), post-nCRT TIL density was marginally higher than that of non-ypT0 group (404 vs. 259, p = 0.050).

Conclusion
Irrespective of clinical responses, PD-L1 expression and TIL density were both increased after nCRT. Our results could help the development of combination strategy of immunologic drugs and seek the possibility of an organ-saving strategy that will contribute to improving quality of life of patients.