bluuebunny/crossref_metadata_2025_split huggingface dataset:
412. COMPARISON BETWEEN PREOPERATIVE MALNUTRITION, AND SARCOPENIA AND POSTOPERATIVE COMPLICATIONS IN ESOPHAGEAL CANCER PATIENTS
Authors: Ozawa Yohei , Taniyama Yusuke , Sato Chiaki , Okamoto Hiroshi , Ishida Hirotaka , Koseki Ken , Shinozaki Yasuharu , Yashima Yoshiyuki , Miura Takuma , Kamei Takashi 
Published: September 2024

Abstract

Background
Typical indicators of malnutrition in cancer patients include BMI, CONUT, PNI, and prealbumin, while SMI and PMI are often used as indicators of skeletal muscle mass loss (sarcopenia). Although these indicators have been reported to be associated with surgical outcomes, their combination may be useful in determining the effectiveness of perioperative management because these are closely related during the perioperative period.

Methods
A total of 132 esophageal cancer patients who underwent esophagectomy between January 2021 and May 2023 were included in this study. Preoperative BMI, CONUT, PNI, prealbumin, SMI (measured by BIA), and PMI (measured by CT imaging) were extracted from clinical record. We also selected BMI and SMI as a new indicator for combined malnutrition and loss of skeletal muscle. Then, we investigated the association between these indicator and postoperative complications (pneumonia, suture failure, total CD Grade ≥II, total CD ≥IIIa), and length of hospital stay.

Results
The mean age of patients was 67.3 years, 107 were male and 25 were female. Preoperative chemotherapy was administered to 58 patients. Although associations with each single index were found for postoperative pneumonia and low BMI, low SMI, and low PMI, there was no significant association with anastomotic leakage or overall complications. On the other hand, low BMI+SMI was strongly correlated with postoperative pneumonia, overall Grade≥II, and Grade≥IIIa complications. In postoperative hospital stay, low BMI, low PNI, and low SMI as single indicators showed a significant increase in hospital stay, while low BMI+SMI showed further statistically significant increase.

Conclusion
In patients who underwent esophagectomy, single index for malnutrition and low skeletal muscle mass may be predictors of postoperative complications respectively. However, because perioperative management is inseparable from nutritional therapy and exercise therapy, composite index of BMI and SMI may be better predictor of therapeutic efficacy of perioperative nutrition and exercise therapy.
431. DISSECTION OF THE SUPRACARINAL MESOESOPHAGUS RECURRENTIAL LYMPHADENECTOMY AND RECURRENT NERVE DAMAGE
Authors: Guerrero Pablo , Navarro Fernando Mingol , Esteban Marcos Bruna , Cruz David Quevedo , Nieto Marta , Sánchez Carmen Gutiérrez , Chicote Cristina Martínez , Urbaneja Francisco Javier Vaqué 
Published: September 2024

Abstract

Background
Currently, an extended mediastinal lymphadenectomy is considered paramount for an accurate cancer staging as well as to improve the oncologic outcomes of patients with locally advanced esophageal cancer. Following the recently described supracarinal mesoesophagus (Cuesta et. al. 2023) allows a complete lymphadenectomy, including the left recurrential area. However, this dissection represents a considerable challenge and could be associated with significant complications. The aim of this study is to analyse if the extended lymphadenectomy guided by the anatomy of the superior mesoesophagus enables a more careful dissection of the recurrent nerves in order to avoid an injury of these structures.

Methods
We prospectively studied all patients in our centre with advanced esophageal cancer, from 2018 to 2023, who underwent esophagectomy and recurrent lymphadenectomy following the surgical plane of the supracarinal mesoesophagus (both unilateral and bilateral). All procedures were performed as curative intent by the same surgeon. We analysed all patients with recurrent nerve lesions and their severity, as well as their implication through the postoperative period and the treatment needed for their repair. In addition, we also studied the number of adenopathies included in the specimen, specifying those that belonged to the recurrential area and its positivity for tumoral cells.

Results
We included 40 patients in our study, 30 men and 10 women with an average age of 65 years. All of them received neoadyuvant therapy previous to the surgery (mostly CROSS and FLOT schemes). There were only 2 patients (5%) who suffered from permanent recurrent palsy, both needing surgical treatment for its correction. Two other patients had mild dysphonia that could be resolved with phoniatric rehabilitation. No fatal outcome occurred secondary to recurrent nerve injury. The median number of adenopathies resected in total was 35, while the median number of adenopathies corresponding to the recurrential area was 5.

Conclusions
In this study we have observed that, following the landmarks of the supracarinal mesoesophagus allows us to perform an extended mediastinal lymphadenectomy reducing the recurrent nerves injury down to only 5%. Even though a lesion of the recurrent nerves could imply a major influence on the quality of life, performing this dissection meticulously could improve the quality of cancer staging, overall and disease-free survival without significantly increasing the risk of recurrent nerve damage. For this reason, the proper knowledge of these anatomical planes of dissection may help improve lymphadenectomies without increasing or even reducing the rate of recurrent nerve injury.
433. UNRAVELLING THE MOLECULAR MECHANISMS BEHIND TUMOUR DIFFERENTIATION IN ESOPHAGEAL ADENOCARCINOMA
Authors: Wilson Gavin , Brar Karanbir , Allison Frances , Allen Jonathan , Bach Yvonne , Cotton James , Wakeam Elliot , Darling Gail , Elimova Elena , Kalimuthu Sangeetha N , Yeung Jonathan 
Published: September 2024

Abstract

Background
Esophageal adenocarcinoma tumors are divided into three grades based on the tumour’s histological differentiation: well, moderate and poor. Poorly differentiated tumours have a worse survival rate than moderate and well tumours. Understanding the molecular programs of this differentiation may lead to the identification of novel therapeutic interventions specific to tumour differentiation. We have utilized laser-capture microdissection to enrich tumour cells followed by gene expression profiling (RNA-seq) to identify gene expression programs and whole genome sequencing for differentiating specific mutations and copy number changes. Collectively, these results will enable us to unravel the molecular drivers of tumour differentiation.

Methods
Laser capture microdissection was applied to N=127 RNA-seq samples from N=74 patients and N=103 from N=81 patients from a mix of primary tumour biopsies, resections, and metastatic biopsies. Most samples have a matching RNA-seq and WGS sample. We used a standard pipeline to analyze the WGS data and produce somatic mutation, structural variant, and copy number calls. The gene expression data was segregated into two sets a test set consisting of N=74 samples and a test set of N=53 samples. Non-negative matrix factorization was used to identify eleven gene expression programs.

Results
Our testing RNA-seq cohort consisted of N=74 samples from N=74 patients with N=4 G1, N=26 G2, N=35 G3, and N=9 missing differentiation data. Our initial goal was to unravel the gene expression programs that correlate with tumour differentiation. Our non-negative matrix factorization analysis yielded 11 gene signatures, N=3 programs enriched in glandular gene expression, N=3 enriched in EMT pathways, N=2 with fibroblasts, and N=3 associated with immune / inflammation genes (not shown) (Figure 1). Moreover, the glandular signatures were associated with G1/G2 and the EMT and fibroblast signatures with G3. Moreover, the glandular 2 signature was associated with HER2 amplifications.

Conclusion
In this work we have begun to unravel the gene expression and genomic changes associated with tumour differentiation. We have found signatures enriched for both G1/G2 and G3 tumours and from these signatures we have observed gene expression heterogeneity within the different tumour differentiation categories. Moreover, the G3 tumours are enriched in fibroblasts despite our laser-capture microdissection. We are currently working on a classification model to predict tumor differentiation from these gene expression programs and are looking to further integrate our whole genome data to find additional genomic drivers.
439. INTEGRATION OF SCRNA-SEQ AND BULK RNA-SEQ TO VALIDATE A PROGNOSTIC ASSOCIATED SIGNATURE IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Chen Long-Qi , Shang Qi-Xin 
Published: September 2024

Abstract

Background
Considerable evidence has identified important targets for esophageal squamous cell carcinoma (ESCC), but its efficacy and the heterogeneity of ESCC are the main causes of treatment failure. Single-cell RNA-sequencing (scRNA-seq) is a powerful tool for analyzing tumor heterogeneity at the single-cell level and helps to better identify potential therapeutic targets.

Methods
ESCC scRNA-seq data were extracted from the Gene Expression Omnibus (GEO) database. Single-sample gene set enrichment analysis (ssGSEA) was performed using the limma package to analyze ESCC-associated prognostic marker genes from ESCC transcriptome data downloaded from the TCGA database and the results were validated with transcriptomic data from 56 ESCC patients in our hospital. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) analyses of prognostic marker genes were performed by GSEA. Then, univariate and multivariate Cox and lasso regressions were performed to further build signatures. Finally, qPCR was used to assess the expression of prognostic marker genes in 5 pairs ESCC samples.

Results
Integrate scRNA-seq (GSE53624) datasets to obtain 13 cell clusters. We characterized single-cell expression profiles of 24076 cell samples and identified 4 marker genes associated with prognosis. Four key prognostic marker genes were trained and validated on the TCGA-ESCA dataset and in 55 patients from our in-hospital cohort to evaluate predictive overall survival (OS) models. Correlation analysis showed that prognostic marker genes were independent of risk clinical characteristics. In addition, we performed Cox regression analysis, suggesting that the 4 prognostic marker genes screened were independent risk factors related to the prognosis of ESCC patients. In addition, qPCR showed that the expression of IER3 and SAA1 was decreased and the expression of CDKN3 was increased in ESCC tissues, while the expression of TINP3 was not significantly different.

Conclusion
We constructed prognostic marker genes by scRNA-seq and validated the model in a large patient population as well as in ESCC tissues, which provides reasonable evidence and valuable resources for prognostic stratification and the study of potential targets for ESCC.
443. IMPLEMENTATION OF A PROTOCOL FOR THE DIAGNOSIS AND MANAGEMENT OF LONG-TERM COMPLICATIONS FOLLOWING ESOPHAGECTOMY AND GASTRECTOMY
Authors: Farhan-Alanie Ziad , Pecorella Ilaria , Shaaban Aly , Vellaiyappan Sundar , Bennett John , Roberts Geoffrey , Fish Thomas , Chinyama Nyara , Smith Ben , Lamb Claire , Grimes Sam , O'Neill John Robert 
Published: September 2024

Abstract

Background
Surgery remains the mainstay of curative pathway treatment for most patients with esophageal and gastric cancer. Both esophagectomy and gastrectomy carry a significant risk of early post-operative morbidity. The gastrointestinal, nutritional, and endocrine effects of surgery can have a significant impact on patients’ quality of life and include small intestinal bacterial overgrowth, pancreatic exocrine insufficiency, bile acid malabsorption, hypoglycaemia, dumping, and others. Early diagnosis and treatment for these consequences of surgery can significantly improve quality of life. We developed a protocol for the investigation and management of patients with symptoms post-esophagogastric resection and implemented this within a nurse-led follow-up clinic.

Methods
A multi-disciplinary team was involved in the design of a protocol for the investigation and management of late effects following esophagectomy or gastrectomy. The protocol was implemented within a nurse-led clinic with prospective follow-up of all patients following resection. Following the introduction of the protocol, patients were divided into two groups; those with symptoms undergoing investigation prior to introduction of the protocol and all patients prospectively following introduction of the protocol in October 2022 to December 2023. The prevalence of patients undergoing investigation and the time from documentation of symptoms to diagnosis and the prevalence of each diagnosis were assessed.

Results
A total of 217 patients were studied, of whom 93 were part of the pre-protocol (symptomatic) group and the remaining 124 were part of the post-protocol prospective group. Within the pre-protocol group, 67 (72.0%) patients underwent investigation for late effects following surgery. The median time between the presentation of symptoms to diagnosis in the pre-protocol group was 7 months.
Within the post-protocol prospective group, 33 (26.6%) patients underwent investigation for late effects following surgery. The median time between the presentation of symptoms to diagnosis in the post-protocol group was 2 months, representing a 71.4% reduction compared to the pre-protocol group.

Conclusion
Gastrointestinal, nutritional, and endocrine effects of esophagectomy and gastrectomy remain common. In symptomatic patients, a protocolised approach to investigation shortened the time to diagnosis and treatment by a median of 5 months. This approach can be successfully employed within a nurse-led follow-up pathway supported by a multidisciplinary team.
448. PREOPERATIVE PEMBROLIZUMAB COMBINED WITH CHEMOTHERAPY FOR THORACIC ESCC WITH CERVICAL LYMPH NODE METASTASIS (PICC-1): A PROSPECTIVE, PHASE 2 STUDY
Authors: Zhang Guoqing , Mu Teng , Wang Junya , Zhao Jia , Li Xiangnan 
Published: September 2024

Abstract

Background
Thoracic esophageal squamous cell carcinoma patients with cervical lymph node metastasis have poor prognosis and less effective of first-line therapy. The PICC-1 study aimed to assess efficacy and safety of the pembrolizumab combined with chemotherapy for patients with cervical lymph node metastasis.

Methods
Preoperative therapy includes pembrolizumab, nab-paclitaxel and cisplatin every three weeks for 2 cycles. The surgery was performed 3-6 weeks after the completion of the preoperative neoadjuvant therapy. Three weeks after surgery, two periods of maintenance therapy were continued with pembrolizumab combined with chemotherapy. Then maintenance treatment was continued with pembrolizumab for a full year. The primary endpoint was the pathologic complete response (pCR) rate. The secondary endpoints included the R0 resection rate, the major pathological response (MPR), recurrence-free survival (RFS), overall survival (OS) and perioperative complications.

Results
As of December 31, 2023, 22 patients who met the criteria were enrolled. All 22 patients suffered from treatment-related AEs of any grade during the neoadjuvant treatment period. The majority of AEs were lymphopenia (72.7%), anemia (59.1%), neurotoxicity (77.3%), nausea/vomiting (77.3%) and leukopenia (40.9%). In 8 of the 22 patients (36.4%), grade III or higher AEs were observed. All the patients underwent thoraco-laparoscopic esophagectomy without intraoperative conversion to open surgery. R0 resection was achieved in 90.9% of patients (20/22). pCR and mPR were observed in 31.8% (7/22) and 13.6% (3/22) of the resected patients, respectively. No patient died postoperatively.

Conclusions
Esophagectomy after neoadjuvant immunochemotherapy is a promising radical treatment for thoracic esophageal squamous cell carcinoma patients with cervical lymph node metastasis. R0 resection was achieved in 90.9% of patients, and pCR was observed in 31.8% (7/22) of resected patients.
450. TISSUE RESIDENT MEMORY CELLS: CORRELATING THE PHENOTYPIC AND FUNCTIONAL CAPABILITIES OF A POTENTIAL TUMOUR REACTIVE CELL POPULATION IN OESOPHAGEAL ADENOCARCINOMA
Authors: Natalie TO , Pearce Hayden , Evans Richard , Croft Wayne , Hejmadi Rahul , Elshafie Mona , Griffiths Ewen , Moss Paul 
Published: September 2024

Abstract

Background
Oesophageal adenocarcinoma (OAC) is a disease with a high mortality and morbidity rate. Immunotherapy has recently demonstrated progress in the treatment of OAC but its impact on long term survival is currently uncertain.
Tissue resident memory (TRM) T cells are a subset of lymphocytes within the tumour/tissue infiltrating lymphocyte (TIL) milieu that has attracted considerable interest within cancer immunology. Although TRM cells have been associated with better outcomes in multiple cancer types there is a lack of knowledge of their role in OAC. This study aims to critically correlate the phenotype of TRM with their functional capacity in this disease.

Methods
33 patients undergoing surgical resection for OAC were recruited and consented for collection of fresh tumour (T), adjacent normal tissue (AN), and peripheral blood. Peripheral blood mononuclear cell (PBMC) from blood and infiltrating lymphocytes from T and AN were isolated using standard density gradient and enzymatic digestion protocols. Multiparametric flow cytometry was performed on 12 patients using matched PBMC, T and AN infiltrating lymphocytes for phenotypic analysis and 21 patients for functional analysis following cell stimulation assay. BD FACSymphony was used for data acquisition and data analysed on FlowJo version 10.10. Statistical analysis was carried out using GraphPad Prism.

Results
TRM (CD103+CD69+) dominated the CD8+ T cell population of T and AN TIL. Expression of checkpoint proteins PD1+ and CD39+, a marker of tumour reactivity, was identified on CD8+ TRM and CD8+ non TRM in TIL. The differentiation status of TRM within memory lineages demonstrated that TRM express a higher proportion of effector memory cells (CCR7-CD45RA) compared to those in blood. TRM cells also showed lower expression of the transcription factors EOMES, TBET and TCF compared to CD8+ cells within PBMC. Moreover, tumour CD8+ TRM populations had reduced ability to produce IL-2 following stimulation compared to adjacent normal TRM populations.

Conclusion
TRM make up a large proportion of CD8+ T cell within the tumour microenvironment (TME) of OAC. TRM generation is associated with the downregulation of T-Box transcription factors EOMES and TBET and expression of an effector memory phenotype with reduction of the stem-like transcription factor, TCF. High levels of CD39+ indicate a strong level of activation but the increased PD1 expression and reduced capability to produce IL2 indicate functional impairment suppressed within the TME. An opportunity may exist to reverse this with novel immunotherapeutic agents.
462. EPIPHRENIC DIVERTICULA. THERAPEUTIC ALTERNATIVES AND OUR EXPERIENCE
Authors: Dominguez Susana Maria Martin , Fernandez Omar Abdel-Lah , Valverde Pedro Antonio Montalban , Parra Juan Sebastian Vargas , Lobo Anton Sanchez , Muñoz Sonsoles Garrosa , Salvador Beatriz Baron , Arranz Juan Manuel Nieto , Perfecto Ricardo Vazquez , Cosido Lourdes Hernandez , Manchado Felipe Carlos Parreño 
Published: September 2024

Abstract

Background
Epiphrenic diverticula account for less than 10% of esophageal diverticula and they are located in the last 10cm, in the right posterior quadrant. They are pseudodiverticula, lacking the muscular layer. Recent studies report that over 75% of these occur concomitantly with esophageal motility disorders, making it essential to evaluate them via manometry before deciding on intervention. Asymptomatic patients usually receive non-operative treatment. Indications for surgical treatment include increased diverticulum size, specific symptoms and suspicion of malignancy. Standard surgical treatment consists of laparoscopic approach with diverticulectomy, myotomy and Dor fundoplication.

Methods
We had 9 cases of esophageal epiphrenic diverticula that required surgical intervention in the last 16 years. In the vast majority of them, laparoscopic diverticulectomy was performed, along with myotomy and Dor fundoplication. Among them, there is a rare case of recurrence of a giant epiphrenic diverticulum in a 55-year-old patient treated with this approach. Due to the complexity of the case, partial esophagectomy and reconstruction with right-sided ascending coloplasty via posterior mediastinal route were decided as definitive treatment.

Results
The outcome was satisfactory in almost all patients, being the most frequent complications a suture line dehiscence and associated mediastinitis.

Conclusion
Esophageal diverticular pathology is uncommon, and its treatment is conservative in most cases. Over 75% of epiphrenic diverticula occur in the context of an underlying esophageal motor disorder. Indications for surgical intervention are the presence of symptoms, increased diverticulum size and suspicion of malignancy. The standard treatment consists in diverticulectomy, myotomy and fundoplication, but there are therapeutic alternatives that should be considered and individualized in each case. Symptoms disappearance after surgical treatment is nearly 90%. However, the procedure carries a morbidity and mortality rate of 20%, being the most common complication a suture line dehiscence, occurring in 33% of cases.
475. MINIMALLY INVASIVE IVOR -LEWIS ESOPHAGECTOMY - ANALYSIS OF PERIOPERATIVE ONCOLOGICAL AND SHORT TERM OUTCOMES
Authors: Parthasarathi R , Palanivelu C , Ramesh N 
Published: September 2024

Abstract

Background
Trans thoracic Ivor-Lewis esophagectomy is the widely adopted procedure for gastroesophageal junction adenocarcinoma. Minimally invasive esophagectomy has been shown to be superior in comparison to the traditional open approach in terms of pulmonary complications and lymph node yield. We present our experience of minimally invasive Ivor-Lewis esophagectomy in this review.

Methods
A retrospective review of the patients who underwent minimally invasive Ivor-Lewis esophagectomy at a single center between September 2009 and April 2023 was performed. The perioperative and short term outcomes were analyzed.

Results
A total of 195 patients [147 males (75.38%)] underwent minimally invasive Ivor-Lewis esophagectomy during the study period. The median (range) age was 62 (48-77) years. The median operative time was 435 (310-530) minutes. The median estimated blood loss was 125 (80-250) ml. R0 resection was achieved in all the patients. The median lymph node yield, ICU stay and overall hospital stay were 22 (12-30), 3.5 (2-12) days and 10 (7-33) days respectively. Pulmonary complications were the most common seen in 24 (12.31%) patients. Anastomotic leak was noted in 5 (2.56%), chyle leak in 2 (1.02%), recurrent laryngeal nerve paresis in 12 (6.15%) patients. Anastomotic stricture was noted in 22 (11.28%) patients who were managed with endoscopic dilatation. Thirty day mortality was observed in 4 (2.05%) patients.

Conclusion
Minimally invasive Ivor-Lewis esophagectomy is associated with good perioperative oncological and short term outcomes when performed in a specialist esophageal center