bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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

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

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
490. THE IMPACT OF ONE-LUNG VENTILATION ON POSTOPERATIVE COMPLICATIONS AFTER IVOR LEWIS ESOPHAGECTOMY
Authors: Battaglia Silvia , Turi Stefano , Puccetti Francesco , Lorenzo Cinelli , Lavinia Barbieri , Treppiedi Elio , Cossu Andrea , Elmore Ugo , Rosati Riccardo
Published: September 2024

Background

One of the most common issue after Ivor Lewis esophagectomy are pulmonary complications, affecting up to 27% of patients, leading to longer hospital stay and higher healthcare costs.

Traditionally, one-lung ventilation (OLV) with a double-lumen tube, is used during the thoracic phase of esophagectomy in order to provide a good surgical view by collapsing the right lung parenchyma. However, OLV has been proven to contribute to negative respiratory outcomes after surgery. On the other hand, a recent metanalysis showed that Two Lung Ventilation (TLV) is feasible throughout the two phases of the procedure, with good clinical, surgical and oncological results.

Methods

A consecutive series of patients undergoing minimally invasive Ivor Lewis esophagectomy (MIIL) between November 2022 and November 2023 in one high-volume center was retrospectively reviewed. Intraoperative ventilation characteristics were analyzed. Postoperative pulmonary complications were stratified according to Clavien Dindo classification and further divided into mild (<3a) and severe (>3b).

Descriptive statistics was used to analyze the study sample. Data was expressed as median and interquartile range (IQR) for non-normally distributed variables and as proportions for binary variables. Categorical variables are expressed as frequencies and analyzed by chi-square (χ2) tests. P-values of < 0.05 defined statistical significance (two-sided).

Results

Of the 70 patients, 8 were excluded due to lack of data. 62 patients were further stratified into three groups considering the ratio between the durations of OLV and the thoracic phase (OLV/TP): group A less than 25% of OLV/TP, group B more than 25% but less than 75% and group C more than 75%.

No difference between the three groups was found in terms of pulmonary complications (χ2=1.6248, p-value=0.4437) whilst patients with a shorter OLV/TP showed a significant reduction in the incidence of severe respiratory complications(χ2= 8.2974, p-value 0.015785, p < 0.05).

Conclusion

Taking into account the limits of the study (retrospective nature, single center study), our results show that the length of OLV may negatively affect postoperative pulmonary outcomes. These promising results justify the need to conduct a randomized controlled study that would be instrumental in reaching definitive conclusions.
505. USE OF INDOCYANINE GREEN FOR ASSESSMENT OF GASTROPLASTY VASCULARIZATION AFTER MCKEOWN ESOPHAGECTOMY
Authors: Lissón Miriam Menéndez Jiménez De Zadava , Navarro Fernando Mingol , Esteban Marcos Bruna , Urbaneja Javier Vaqué , Nieto Marta
Published: September 2024

Background

Anastomotic leakage is one of the most feared complications of esophagogastric surgery, conferring significant morbidity and mortality in these patients. It is known that inadequate vascularization of the gastroplasty is a major risk factor for anastomotic dehiscence. The aim of this study is to evaluate and demonstrate the utility of intraoperative use of indocyanine green (ICG) in patients undergoing esophagectomy and reconstruction with gastroplasty to assess the relationship between its vascularization and the presence of anastomotic leakage in the postoperative period.

Methods

Prospective, longitudinal, observational, and analytical study of 36 consecutive cases in which intraoperative ICG was used for patients undergoing McKeown esophagectomy and reconstruction with gastroplasty and cervical anastomosis from June 2021 to December 2023. The distance traveled by the ICG in a proximal direction from the pylorus at 30 and 90 seconds after its intravenous infusion was measured. An automatic baseline point or point of maximum fluorescence was also recorded and compared both in net value and in percentage at 30, 60, 90, and 120 seconds after the infusion of ICG with the theoretical zone of anastomosis construction (zone reaching the sternal manubrium after extending the graft over the sternum). Statistical analysis was performed using SPSS version 24.0.

Results

The rate of leaks and necrosis of the graft was 19.4% and 2.8%, respectively. There is a significant relationship (p<0.05) between the rate of anastomotic dehiscence and the net value and percentage compared with the automatic baseline point of ICG at the anastomosis site and at the apex of the gastroplasty at 30, 60, 90, and 120 seconds. Using a ROC curve (figure 1) that analyzed the time it takes for ICG to reach the anastomosis, a cutoff point of 19.5 seconds was established, which gives ICG greater profitability as a diagnostic test with an AUC of 0.821 (0.642-1). The positive predictive value of this test is 0.36, and the negative predictive value is 1.

Conclusion

The use of indocyanine green appears to be a good method for identifying those anastomoses and gastroplasties that present a high risk of dehiscence and/or necrosis. The time it takes for ICG to reach the anastomosis, the speed at which it does so, as well as the quantitative value provided by the platform used, seem to be valid parameters for identifying high-risk cases. This would allow for the performance of additional measures to reduce the risk of dehiscence and/or necrosis. Randomized prospective studies with a larger sample size would be necessary.
514. ESOPHAGOGASTRIC ANASTOMOSIS STRICTURE AFTER A CERVICAL FISTULA: LONG TERM COMPLICATION AFTER THE MCKEOWN PROCEDURE STERNOTOMY APPROACH: ANASTOMOSIS RESECTION
Authors: Cruz David Quevedo , Navarro Fernando Mingol , Antolino Pablo Guerrero , Nieto Marta , de Zadava Lisson Miriam Menendez Jimenez , Esteban Marcos Bruna , Urbaneja Javier Vaque
Published: September 2024

Background

Anastomotic stricture after anastomotic leakage is a common long term complication after mckeown procedure. It can be resolved by endoscopic dilations on most occasions. However, if endoscopic aproach fail, we have to solve the estenosis with a surgery procedure.

This type of reintervention could be a really hard aproach due to an intense fibrosis and anatomical layer destructuring.

In this video, we show a initial cervical approach to do a anastomosis resection and reanastomosis. However, due to the intense fibrosis and the difficulty in dissecting the gastric plasty from the sternal table, the incision had to be extended and a partial sternotomy was performed. With this approach, we can see the gastric plasty, making the dissection. The we can perform a new esophagus gastric anastomosis safety.

In conclusion, partial sternotomy allows us to visualize the gastric plasty and perform the dissection safety making a tensión free anastomosis.

https://we.tl/t-6MTce26lI1
519. ROBOTIC HELLER DOR FOR SYMPTOMATIC ACHALASIA. A SINGLE TERTIARY CENTER EXPERIENCE
Authors: Sacco Michele , Bencivenga Maria , Casella Francesco , Cucè Federica , Weindelmayer Jacopo , de Manzoni Giovanni , Giacopuzzi Simone
Published: September 2024

Background

Minimally invasive Heller-Dor is the best therapeutic option for symptomatic achalasia.

The aim of this study is to describe the introduction of Robotic program for Heller-Dor procedure (RAHD) in a tertiary center evaluating clinical and surgical outcome.

Methods

We performed a retrospective analysis of patients diagnosed with symptomatic achalasia through clinical, endoscopic, and manometric workup, that were eligible for RAHD. We included all consecutive patients underwent RADH between September 2019 and December 2023 using the DaVinci Xi surgical system. Patients with previous endoscopic or surgical treatment for achalasia were excluded.

Results

Data from 44 patients were collected. Patients’ characteristics are summarized in table 1.

Most patients were in good clinical condition with an ASA score 1-2 and a CCI 1-2 in more than 80% of cases.

Mean Eckhardt score (ES) was 6 (SD 2.05). Most frequent symptom was dysphagia, present in all patients but with different severity.

Mean operating time was 184 minutes (SD 46).

Mucosal tear occurred in three cases and all were sutured immediately, an abdominal drain was placed only in the first case. A regular postoperative course was observed in all patients.

All patients underwent a post-op gastrografin esophagogram before starting a liquid diet; none revealed leakage or treatment failure.

Three patients (6,8 %) experienced Clavien-Dindo grade I complication, one hepatic hematoma, one pneumothorax, and one PONV. No severe complications were reported.

Maximum length of hospital stay was 4 days, mean 3.2 (SD 0.42).

All patients were discharged with a well-tolerated soft diet.

Mean ES at follow up was 0.58 (SD 0.7) at 1 months. After 6 months and 1 year, no patients reported recurrence of symptoms (ES <3), but three patients reported symptomatic reflux (6,8%).

Conclusion

Our experience suggests that introduction of RAHD is safe and effective in the treatment of symptomatic achalasia in a tertiary center for Upper Gastrointestinal Surgery.
521. SHORT-TERM PROPHYLACTIC STENTING FOR HIGH-RISK ESOPHAGEAL ANASTOMOSIS: A CASE SERIES
Authors: Clements Hollie A , Zino Samer , Oglesby Stuart , Patil Pradeep V
Published: September 2024

Background

Anastomotic leak after esophagectomy is a cause of major morbidity, increases surgical mortality and can affect long-term survival outcomes. Early recognition and treatment of anastomotic leaks has greatly improved the rescue rates for this catastrophic complication. However, for some patients, successful rescue is not sufficient to prevent major morbidity and worse long-term outcomes. Prevention of esophageal anastomotic leaks would benefit these patients. Prophylactic stenting after esophagectomy can be one of the tools used in addition to all other factors that are implemented to improve surgical outcomes in this complex cohort of patients.

Methods

We present a series of seven patients who underwent esophagectomy for malignant disease at our institution. They had insertion of prophylactic esophageal stents at the time of esophagectomy due to a combination of patient factors and intraoperative complications. All anastomoses were carried out using the modified Orringer technique of linear stapled esophagogastric anastomosis. All patients underwent insertion of an 18mm diameter, fully covered EGIS (S&G Biotech, Korea) esophageal stent with antireflux valve. This was fixed to the esophagus / gastric tube using two 2-0 Vicryl Rapide (Polyglactin 910) sutures. The stents were removed endoscopically between postoperative day 14 and 28.

Results

None of the seven patients who underwent prophylactic esophageal stenting had any clinical or radiological evidence of anastomotic leak. In one patient, at the time of stent removal, a possible anastomotic defect was noted but it was not possible to enter the cavity. A new stent was inserted, and the patient was clinically observed. He remained clinically well throughout. Another patient developed a severe hospital acquired pneumonia requiring ventilatory support without evidence of anastomotic leak. Median length of stay was 13 days. There was no mortality within 90 days of surgery.

Conclusion

Short term prophylactic esophageal stenting is possible and safe. The technique of stent fixation and early removal helps to mitigate the risks of stent migration and erosion. In our small series, the stents were effective in preventing anastomotic leaks with no stent related complications. This provides optimism for patients and surgeons that morbidity from anastomotic leaks can be minimised, enabling patients to recover from surgery and proceed to adjuvant treatment if indicated. The safety profile of prophylactic esophageal stents should be investigated further and both short- term and long-term outcomes compared to current standards of care by randomised studies.
524. SURVIVAL AFTER CURATIVELY INTENDED TREATMENT OF ESOPHAGEAL CANCER IN THE NORDIC COUNTRIES
Authors: Norén Nora , Achiam Michael Patrick , Aahlin Eirik Kjus , Kauppila Joonas , Vidarsson Bjarni Geir , Klevebro Fredrik
Published: September 2024

Background

Esophageal cancer is the 6th leading cause of cancer related death and has a high impact on life quality. With the ambition to improve long-term survival multimodal treatment including chemotherapy, or combined chemoradiotherapy, followed by surgical resection has become the standard of care. The overall aim of this study is to demonstrate the current treatment of esophageal cancer and survival in the Nordic countries.

Methods

In this cohort study based on prospective national patient registers all patients with esophageal cancer treated with curative intent between 2015-2020 in Sweden, Denmark, Norway, Finland and Island were included. Primary endpoint is 1-year survival after curative treatment for esophageal cancer. Secondary outcome is to describe curative intended treatment for esophageal cancer in the Nordic countries.

Results

The results will describe baseline characteristics, curative treatment including details of the surgical and perioperative treatment, and survival stratified by country.

Conclusion

The conclusion will describe the current curative treatment of esophageal cancer in the Nordic countries.
553. CIRCULAR STAPLED CERVICAL ESOPHAGO-GASTROSTOMY, A VALUABLE OPTION AFTER TOTALLY MINIMALLY INVASIVE MCKEOWN ESOPHAGECTOMY?
Authors: Pansa Andrea , Giorgi Lorenzo , Di Benedetto Mattia , Alfieri Rita , Basato Silvia , Marano Salvatore , Castoro Carlo
Published: September 2024

Background

The optimal choice of anastomotic technique for cervical esophagogastric anastomosis after esophagectomy remains unclear. The incidence of cervical anastomotic leak after esophagectomy can be up to 30%, which is the highest among all types of gastrointestinal anastomosis. Anastomotic stricture is another complication that can decrease the postoperative quality of life with an incidence of 9.1–46.0%. Few studies directly compared circular stapled (CS) and hand sewn (HS) cervical esophago-gastric anastomosis, with mixed results. We aim to compare the two techniques in a pre-post cohort study.

Methods

Medical record of all patients that underwent minimally invasive subtotal esophagectomy and cervical esophago-gastrostomy in our institution from January 2018 to January 2024 were reviewed from a prospectively collected database. We routinely performed hand sawn anastomoses until February 2022, then switched to circular stapled, with the aim of reducing the incidence of anastomotic leaks. We compared clinical data of patients who received hand sewn cervical anastomosis and circular stapled anastomosis. Primary endpoints were anastomotic leaks and strictures.

Results

We identified 101 patients who met the inclusion criteria. HS anastomosis was performed in 67 patients, while 34 received CS anastomosis. Anastomotic leak rate was 22.4% in the HS group and 8.8% in the CS group (OR 0.34, p=0.092). Anastomotic stricture rate was 26.9% in the HS group and 14.7% in the CS group (OR 0.47, p=0.17). Median length of stay was 18 (IQR 15-22) days in the HS group and 13.5 (IQR 12-14.5) days in the CS group (p=0.001). Severe complication rate (CD>2) was 16.4% in the HS group and 11.8% in the CS group (OR 0.68, p=0.53).

Conclusions

In our experience, the introduction of circular stapled cervical esophago-gastrostomy was feasible and safe, and resulted in a lower incidence of anastomotic leak and stricture compared to hand sewn anastomosis, though not statistically significant, possibly because of the small sample size. No difference in other major postoperative outcomes was observed. We found cervical CS anastomosis a reliable, reproducible and technically less demanding procedure, even for very high esophageal cancers. We believe that this anastomotic technique could spread even in Western countries where it has hardly ever been explored.
554. SHORT TERM OUTCOMES OF ESOPHAGECTOMY FROM LOW VOLUME CANCER CENTRE IN INDIA
Authors: Nittala Rigved , Padhy Amita Sekhar
Published: September 2024

This study evaluates short term outcomes of esophagectomy at a low volume cancer hospital in Visakhapatnam, India. Fifteen patients who underwent esophagectomy from 2020 to 2023 were analysed. The most common histology was squamous cell carcinoma. The mean age was 55 years and the majority were male. The common approaches used were open trans hiatal and transthoracic esophagectomy. The mean operative time was 9.5 hours and the mean hospital stay was 15.92 days. There were no perioperative deaths but complications included pulmonary issues, vocal cord paralysis, anastomotic leaks, chyle leaks and wound infections. Higher volume centres tend to have better outcomes after esophagectomy. However, factors other than volume like patient selection, ERAS (Enhanced Recovery After Surgery) protocols, specialized critical care and trained multidisciplinary teams also impact outcomes. At our centre, though a low volume hospital, proper patient selection, prehabilitation and a collaborative team approach helped achieve acceptable results. We recommend developing consensus on defining low and high-volume centres for esophagectomy in the Indian context, based on disease burden, resources and constraints. Overall, there is a lack of Indian data comparing outcomes between low and high-volume centres for esophagectomy.
564. PRONE POSITION THORACOSCOPIC HAND-SEWN ESOPHAGO-GASTRIC ANASTOMOSIS DURING 2-STAGE TOTALLY MINIMALLY INVASIVE ESOPHAGECTOMY FOR CANCER. SURGICAL TECHNIQUE
Authors: Davakis Spyridon , Liakakos Theodoros , Charalabopoulos Alexandros
Published: September 2024

Background

Minimally invasive esophagectomy has been introduced in the 2000s in an effort to reduce post-operative pulmonary and cardiac complications. 2-stage totally minimally invasive esophagectomy combines laparoscopic abdominal phase followed by thoracoscopic thoracic phase. The rate limiting step of this approach is the construction of esophago-gastric anastomosis. Herein, we aim to present our anastomotic technique on hand-sewn esophago-gastric anastomosis in prone position, utilizing 3D-assisted thoracoscopy.

Methods

This is prospective analysis of consecutive patients that underwent 2-stage totally minimally invasive esophagectomy for esophageal and gastro-esophageal junction Siewert type I-II cancers from the same surgical team, over a period of 6 years and more than 250 consecutive esophagectomies. All operations were identical in terms of patient positioning, lymphadenectomy and type of anastomosis formed. The anastomosis was hand-sewn in prone position, in 2-layers, using barbed sutures, with utilization of 3D-assisted thoracoscopy. Thorough technique and key steps of this anastomotic technique are provided.

Results

Median operative time was 280 minutes while median suturing time for the esophago-gastric anastomosis was 45 minutes. Anastomosis was thoracoscopic, hand-sewn constructed in prone position in all cases. There was no conversion to open. Anastomotic leak complicated n=6 patients (2%); n=5 were type I anastomotic leaks, requiring no intervention and n=1 was type II, which was treated with thoracoscopic lavage and chest drains followed by endoVAC therapy.

Conclusion

Formation of the esophago-gastric anastomosis is the rate limiting step of 2-stage totally minimally invasive esophagectomy. Most surgeons prefer the construction utilizing mechanical staplers. Our anastomotic technique, present a safe and effective anastomosis, with favorable clinical outcomes. It can be reproduced safely and effectively, offering all the advantages of manual anastomosis and significant reduction of devastating post-operative anastomotic leakage.

https://wetransfer.com/downloads/bdf3a3496197daf79ccf5b05f71ba64920240309175850/a4da3be742fd3199e102e553c8a4011e20240309175918/c14cc2
578. DUPILUMAB EFFICACY IN EOSINOPHILIC OESOPHAGITIS PATIENTS TREATED WITH PRIOR THERAPY AND INADEQUATE RESPONSE, INTOLERANCE, OR CONTRAINDICATION TO SWALLOWED TOPICAL CORTICOSTEROIDS
Authors: Cianferoni Antonella , Dellon Evan S , Schlag Christoph , Xia Changming , Durrani Sandy , Pela Tiffany , Radwan Amr , Jacob-Nara Juby A
Published: September 2024

Background

Improvements in histologic, symptomatic, and endoscopic aspects of eosinophilic oesophagitis (EoE) were observed in patients treated with dupilumab weekly (qw) enrolled in the 3-part, phase 3 LIBERTY EoE TREET study (NCT03633617), regardless of prior inadequate response, intolerance, and/or contraindication to swallowed topical corticosteroids (STC). Here we assess the efficacy of dupilumab qw versus placebo in this STC non-responsive/intolerant subgroup, stratifying further by those with/without history of food elimination diets, proton pump inhibitor (PPI) use at randomisation, or history of oesophageal dilation.

Methods

This analysis includes patients who received dupilumab 300 mg qw or placebo for 24 weeks in Part B and an additional 28 weeks dupilumab in Part C. Co-primary endpoints (Weeks 24 and 52) include: proportions of patients achieving peak eosinophil count (PEC) ≤6 eosinophils/high-power field (eos/hpf) and absolute change in Dysphagia Symptom Questionnaire (DSQ) score. Secondary endpoints assessed included proportions of patients achieving PEC ≤1 eos/hpf, <15 eos/hpf, % change in PEC, and absolute change in Endoscopic Reference Score, and EoE-Histologic Scoring System grade/stage scores.

Results

Dupilumab 300 mg qw improved proportions of patients achieving co-primary endpoints, ≤6 eos/hpf and absolute change in DSQ score, and secondary endpoints, ≤1 eos/hpf and <15 eos/hpf at Week 24 versus placebo, regardless of history of food elimination diets, PPI use at randomisation, or history of dilation (Table). Improvements were maintained or continued to improve at Week 52. A similar trend was observed for other secondary endpoints assessed. Placebo-treated patients who switched to dupilumab in Part C demonstrated similar efficacy to patients treated with dupilumab in Part B. Dupilumab safety was consistent with the known dupilumab safety profile.

Conclusion

Dupilumab qw demonstrated sustained improvements in histologic and symptomatic aspects of EoE up to 52 weeks in adults and adolescents with an inadequate response, intolerance, and/or contraindication to STC, regardless of history of food elimination diets, PPI use, or history of oesophageal dilation. Improvements in endoscopic aspects of EoE up to 52 weeks were also observed.
580. ESTABLISHMENT OF A RAT MODEL OF GASTROESOPHAGEAL REFLUX DISEASE INDUCED CHRONIC MICROASPIRATION
Authors: Masuda Takahiro , Kawamura Akira , Kurogochi Takanori , Shimoda Masayuki , Sakashita Yuki , Omura Nobuo , Yano Fumiaki , Eto Ken
Published: September 2024

Background

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder in Japan, the world’s first super-aging society. Occult microaspiration due to GERD can cause respiratory infections especially in frail elderly individuals. The aim of the study was to establish an experimental in vivo model of GERD induced chronic microaspiration.

Methods

GERD was induced in 8-week-old male Wistar rats. A 2-cm midline incision was made in the upper abdomen. The border between the forestomach and the glandular portion (limiting ridge) was ligated with a 2–0 silk tie, and the duodenum near the pyloric ring was covered with a 2-mm-wide piece of an 18-Fr Nélaton catheter. CT scan and histopathological evaluation of the bilateral lungs were performed at 3 weeks after surgery.

Results

The 3-week survival rate was 80% (n=4/5). CT scan showed diffuse dilatation of the esophagus due to the reflux of gastric contents; however, there was no consolidation in the lungs similar to the healthy control. Based on macroscopic evaluation, the lungs had multiple spotted redness. Histopathological evaluation of hematoxylin and eosin staining showed multiple spotted aspiration pneumonia with peribronchiolar inflammatory cells, granuloma formation, goblet cell hyperplasia.

Conclusions

This model mimics human occult chronic microaspiration due to GERD, and may be useful in the investigation of drug efficacy and the evaluation for pathophysiology of GERD induced pulmonary disorders.
594. THE IMPACT OF PATIENT CHARACTERISTICS AND NEOADJUVANT TREATMENT ON THE TUMOUR MICRO-ENVIRONMENT OF ESOPHAGEAL CANCER
Authors: Fasquelle François , Teixeira-Farinha Hugo , Sempoux Christine , Worreth Sandrine , Piazzon Nathalie , Schäfer Markus , Mantziari Styliani
Published: September 2024

Background

Esophageal cancer remains associated with poor prognosis, as even with the current standards of multimodal treatment and oncologic surgery many patients show no response to treatment, or suffer early recurrence after surgery. In the current era of precision medicine, a better understanding of the tumor microenvironment (TME) is needed to identify patients with unfavourable biology, but also to illustrate the physiopathology of host reaction to treatment. The aim of this monocentric translational study was to analyse the biomolecular characteristics of esophageal cancer in relation to key clinicopathologic parameters, and in particular to the response to neoadjuvant treatment.

Methods

A series of patients operated for esophageal cancer with curative intent between 01.2009 and 12.2021 were included in this study. Clinicopathological data were collected, and initial biopsies and surgical specimens were reassessed by a senior GI pathologist. The immune infiltrate markers CD3, CD8, CD163, CD68, PDL1and FOXP3 were recorded as cell counts/high power field. The CPS score was used for PD-L1 quantification, whereas the Mandard regression grade (TRG) assessed pathologic response to neoadjuvant treatment (NAT). Continuous variables were compared with the Mann-Whitney-U and ANOVA tests, and categorical ones with the Chi-2 test. Significance threshold was set at p<0.05.

Results

Overall, 68 patients (82.4% males, mean age 62.4□9.4 years, 79.4% adenocarcinoma) were included. TME in smokers had lower M2-like (CD163+, p=0.009) and total macrophages (CD68+, p=0.001), but similar CD163/68 ratio and T-cells as non-smokers. Adenocarcinoma histology compared to squamous cell, showed higher M2-like macrophages (p=0.023), mean CPS score (p=0.038) and T-cell infiltration (p=0.006). NAT increased macrophages and cytotoxic T-cells, and decreased Treg/FoxP3 cells in the TME. Chemotherapy, compared to chemoradiation, was associated with higher T-cell TME infiltration. Good responders to NAT (TRG1-2) had similar initial TME characteristics as poor responders, but they displayed lower macrophage count upon final histology (p=0.003).

Conclusions

In the present series, active smoking was related to attenuated, whereas adenocarcinoma histology to enhanced M2-like macrophage infiltration of esophageal cancer TME. Neoadjuvant treatment, and especially chemotherapy, recruited macrophages and T-cells in the TME. None of the biomarkers derived from the initial biopsies were associated with response to NAT, although an increased macrophage count upon final histology was related to poor response. The present study provides valuable insight to the TME composition of esophageal cancer. However, further studies are needed to assess the exact functional role of TME elements, and specifically macrophages, and their impact on clinical outcomes.
599. ASSESSMENT OF BREATHING MECHANICS IN OESOPHAGEAL CANCER SURVIVORS USING A 3D-MOTION CAPTURE SYSTEM
Authors: Tukanova Karina , Banger Matthew , McGregor Alison , Hanna George , Markar Sheraz
Published: September 2024

Background

Traditional open surgery is characterised by an intercostal incision. The associated ribcage injury may precipitate the development of post-thoracotomy-related pain, with impaired respiratory muscle contraction, leading to compromised coughing and decreased lung volumes. These changes in breathing mechanics may precipitate pulmonary complications, occurring in up to 40% of the patients. There is however no data available on the long-term breathing function and its implications on the health-related quality of life following oesophagectomy.

This proof-of-concept study aimed to objectively measure breathing movements using a 3D-motion capture system and to understand the impact of surgery on breathing patterns in oesophageal cancer survivors.

Methods

Oesophageal cancer survivors who were disease-free for at least 1 year postoperatively and healthy controls were included. Participants completed quality-of-life (QoL) questionnaires, including EORTC QLQ-C30, -OG25 and LASORS. Eighty-nine retroreflective markers were affixed to the participants' trunks to measure respiratory movements via the Vicon motion capture system during handheld spirometry performance. The highest spirometry value was recorded for the slow inspiratory (SIVC) and forced expiratory vital capacity (FEVC). Concurrent movement data was obtained from adjacent surface markers connected to the midpoint, allowing evaluation of the total volumetric movement of the trunk, and thoracic and abdominal contributions.

Results

Eighteen patients (median age 68) and 22 controls (median age 29) were included. Patients exhibited a significantly reduced SIVC alongside decreased chest movement contribution (median 2.4519 litres IQR 0.9270) compared to controls (median 3.1492 litres, IQR 1.8381) (p=0.013). Meanwhile, patients also had significantly lower FEVC with lower abdominal movement (median 1.5134 litres, IQR 0.7852) compared to controls (median 2.1263 litres, IQR 0.8740) (p=0.039).

The QoL amongst patients was significantly worse for half of the EORTC domains, including physical functioning, fatigue, dyspnoea, pain and discomfort, and coughing (p<0.05). Additionally, the QoL of patients was consistently lower across all LASOR domains (p<0.05).

Conclusion

Current data showed lower spirometry parameters and breathing movements amongst oesophageal cancer survivors, suggestive of impaired breathing mechanics. Specifically, chest expansion was compromised during slow inhalation, while abdominal contraction was reduced during forced exhalation. These findings suggest restrictive changes in breathing mechanics