bluuebunny/crossref_metadata_2025_split huggingface dataset:
317. PD-L1 DYNAMICS DURING THE CISPLATIN-INDUCED ACQUIRED RESISTANCE PROCESS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Cong Qi , Liu Zhichao , Ma Ning , Yu Boyao , Zhu Kaiyuan , Yuan Chang , Yang Yuxin , Jiang Chao , Li Zhigang 
Published: September 2024

Abstract

Background
Immunotherapy combined with chemotherapy has been the first-line treatment and the most widely-used neoadjuvant regimen in esophageal squamous cell carcinoma (ESCC). Resistance to chemotherapy is an inevitable clinical problem, however, the impact of chemoresistance on immunotherapy efficacy remains unclear. This study aimed to investigate the impact of chemoresistance formation on PD-L1 dynamic changes both in vivo and in vitro during the construction of cisplatin-resistant ESCC models, with the goal of exploring the potential influence of chemoresistance on immunotherapy.

Methods
For in vivo model, fluorescent-labeled ESCC cells (AKR) were implanted into C57 mice, followed by cisplatin administration for six cycles. Surviving tumor cells were isolated using flow cytometry, and reinjected to establish cisplatin-resistant model. Tumors were harvested to evaluate PD-L1 expression by immunohistochemistry. For in vitro model, ESCC cell lines (TE-1, KYSE150) received low-dose cisplatin for 48h. After three cycles, resistance index (RI, RI=IC50 of drug-expose cell/IC50 of parental cell) was determined by CCK8 assay. The process was repeated with escalating cisplatin doses until resistant cell lines were established (RI&gt;5). PD-L1 expression was measured using RT-qPCR/Western-Blot after each generation.

Results
In vivo (Figure A), cisplatin-resistant tumor exhibited elevated PD-L1 expression compared to control group (H-score: 22.17 vs 2.09, p&lt;0.001). In vitro (Figure B), PD-L1 expression exhibited an initial increase, followed by a gradual decrease during the process of cisplatin-induced resistance. Specifically, in early stages of cisplatin-resistance in TE-1 cells, PD-L1 mRNA expression rose 4.9 times, consistently paralleled by an elevation in protein level. Subsequently, PD-L1 expression gradually decreased in both mRNA and protein levels. KYSE150 cells exhibited a trend of upregulation in PD-L1 expression in the early stages of cisplatin resistance but later decreased, returning to parental cell levels.

Conclusion
Under in vivo conditions, acquired cisplatin-resistance in ESCC cells significantly upregulated PD-L1 expression, indicating a potential mechanism for PD-L1-mediated immune escape and its impact on immunotherapy efficacy. However, under in vitro conditions, no consistent trend in PD-L1 expression was observed during the acquisition of cisplatin resistance. This suggests a potentially crucial role of the immune system involved in the chemoresistance regulatory mechanism. Further investigations are needed to explore the impact of chemoresistance on tumor immunology.
324. A RETROSPECTIVE SINGLE CENTRE PROPENSITY-MATCHED ANALYSIS OF TRANSTHORACIC VERSUS TRANSABDOMINAL PROCEDURES FOR GIANT HIATAL HERNIAS
Authors: van den Hauwe Lukas , Ovaere Sander , Van Veer Hans , Moons Johnny , Nafteux Philippe , Depypere Lieven 
Published: September 2024

Abstract

Background
Transthoracic open procedure (TTO) was historically the preferred approach for treatment of giant hiatal hernias. However, the last decades transabdominal laparoscopic procedures (TAL) became the standard approach in many centres. The aim of the study was to compare short-term and midterm outcomes, as well as patient-reported outcome measures (PROMs, between TTO and TAL for giant hiatal hernias.

Methods
A retrospective analysis was conducted on all primary surgeries performed for giant hiatal hernias between 2008 and 2022. Patients who underwent TAL were propensity-matched (n= 36) to those who underwent TTO based on: age, gender, Charlson Comorbidity Score and hernia type. The two groups were compared in terms of surgery duration, length of stay (LOS), Clavien-Dindo score, intrahospital reoperation, hernia recurrence and need for reinterventions. PROMswere compared between total of TTO (n= 187) and TAL (n= 48): for symptom score, QoL-score, overall satisfaction and wound pain. Median clinical follow-up was 365.5 days. Median PROMsfollow-up was 55.3 months.

Results
Surgery duration (224 vs 177min, P&lt;0.001) and LOS (11 vs 4days, P&lt;0.001) were longer in TTO. Clavien-Dindo scores were alike (P= 0.260). Intrahospital reoperation was not statistically different (8.3% vs 0%, P= 0.239). Midterm recurrence rates suggested a non-significant trend towards lower recurrence in TTO (2.8% vs 16.7%, P= 0.107). Reintervention rates were alike (16.7% vs 11.1%, P= 0.735). QoL-score was inferior for TTO (0.705 vs 0.355, P= 0.036). Wound pain scores were higher in TTO (1 vs 0, P &lt;0.001). Symptom score and satisfaction scores were alike, respectively 0.685 vs 0.760, P= 0.688 and 9 vs 9, P= 0.421.

Conclusions
TAL for giant hiatal hernias showed superior results compared to TTO for duration of surgery, length of hospital stay, QoL-score and wound pain scores. However, midterm results showed a noticeable trend towards higher recurrence rates for TAL. TAL should be considered when proceeding with surgery for giant hiatal hernias but a possible higher risk of recurrence must be taken into account. Further long-term clinical follow-up and comparison to PROMscould guide future decision-making.
341. EXCISION OF EPIPHRENIC DIVERTICULUM WITH CARDIOMYOTOMY AND FUNDOPLICATION
Authors: Ong Suet Yan , Tan Audrey Poh Poh , Ng Annalisa Ya-Lyn , Lee June , Wong Andrew Siang Yih 
Published: September 2024

Abstract

Background
Epiphrenic diverticulum, a type of pulsion diverticulum, is a rare esophageal diverticulum that occurs in up to 2% of the population. It is commonly located in the distal esophagus, 4 to 8 centimeters (cm) above the gastric cardia. Etiology includes raised intraluminal esophageal pressure and is often associated with an underlying esophageal motility disorder. Indications for surgical intervention depends on presence of symptomatic disease including worsening dysphagia, food retention, regurgitation and complications such as aspiration pneumonia. This video illustrates the surgical management of epiphrenic diverticulum and associated surgical outcomes.

Methods
60-year-old male initially presented with symptoms of dysphagia, food regurgitation and reflux. Gastroscopy performed identified a large esophageal diverticulum, 3cm from cardioesophageal junction (CEJ) and barium swallow study as well as high resolution manometry verified normal esophageal motility. Biopsies did not show any dysplasia. Patient subsequently underwent laparoscopic excision of epiphrenic diverticulum, cardiomyotomy and anterior 180 degrees fundoplication. Intra-operatively, epiphrenic diverticulum was noted on right lateral aspect of esophagus with a 3cm wide neck, 3cm from CEJ. Diverticulum was resected using a linear stapler and cardiomyotomy was perfomed on the contralateral side along with a partial fundoplication.

Results
Patient had an uneventful post-operative recovery with no post-operative complications. Histology confirmed esophageal diverticulum with no dysplasia or malignancy seen. Water soluble contrast study performed on post-operative day 1 and 1 year later demonstrated smooth passage of contrast with no hold up. There was also complete resolution of presenting symptoms on follow-up reviews.

Conclusion
Epiphrenic diverticulum is a rare entity but may present with debilitating symptoms that can affect patient’s quality of life and function. Management of symptomatic patients involves resection of the diverticulum as well as a myotomy and fundoplication to address any underlying motility disorder. This case aims to illustrate the efficacy and positive surgical outcomes that can be achieved with this combined surgical approach.
https://www.dropbox.com/scl/fi/v6ow104q16lgfjhdqajix/Diverticulum-excision-v6.mp4?rlkey=nlmta6y835myqzf2rdf9mqocm&dl=0
345. PERI-OPERATIVE SELECTIVE DECONTAMINATION OF THE DIGESTIVE TRACT TO PREVENT SEVERE INFECTIOUS COMPLICATIONS AFTER ESOPHAGECTOMY: A RANDOMIZED MULTICENTER CLINICAL TRIAL
Authors: Grootenhuis Justin , Seurs Ward , De Vries Marjan , Deckers Karin , Rosman Camiel , Schouten Jeroen , van Veer Hans , Klarenbeek Bastiaan , Ubels Sander 
Published: September 2024

Abstract

Protocol presentation
Rationale: Esophagectomy is a complex surgical procedure, associated with significant morbidity and mortality rates. Most postoperative complications are caused by infections (10–30%). These are thought to arise from (micro-)aspiration of bacteria residing in the oropharyngeal and gastrointestinal (GI) tract, leading to (respiratory) infections. Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic strategy that aims to prevent postoperative infections. Pathogenic aerobic gram-negative rods and yeasts are reduced, while anaerobic, protective microbiota are preserved. SDD has been shown to lower the risk for respiratory infections in an intensive care setting. Establishing SDD as effective addition to the standard care of esophagectomy patients is expected to increase their chance of survival.

Objective
Robust and prospective evaluation of SDD after esophagectomy as a protective strategy reducing postoperative pneumonia and other infectious complications, anastomotic leakage and mortality.

Study design and population
A randomized, controlled, open-label, multicentre trial, including 854 patients with primary resectable esophageal carcinoma ((y)cT1-4a N0-3 M0) planned for transthoracic esophagectomy.

Intervention
The intervention group receives SDD treatment additional to standard care. An oral suspension (10ml) containing amphotericin B (50 mg/ml), colistin sulphate (10 mg/ml), and tobramycin (8 mg/ml). Patients take the oral suspension four times daily for one week, starting three days prior to the surgery. On the day of surgery, intake is limited to an early morning and a late evening dose. All other facets of care are equal to the control group (standard care without SDD). Two microbial samples will be taken from the esophageal resection specimen (one proximal and one from the distal part) for culture to evaluate effectiveness and compliance of SDD application in control as well as in the intervention group. Furthermore, all participants will be asked to keep a diary.

Main study parameters
The cumulative incidence of postoperative pneumonia within 30 days after surgery.

Secondary study parameters
The cumulative incidence of all postoperative complications and re-operation within 30 days after surgery, all- cause mortality within 90 days, length of stay and readmissions within 6 months and quality of life, direct and indirect costs; a week before, 30 days-, 3 months and 6 months after surgery.
356. TUMOUR BURDEN CORRELATES WITH THE RISK OF RECURRENCE AFTER PIECEMEAL ENDOSCOPIC RESECTION OF EARLY-STAGE ADENOCARCINOMA IN BARRETT’S OESOPHAGUS
Authors: Hattersley Grace , Hadjinicolaou Andreas , Sorge Andrea , Conceicao Daniel , Pan Sally , Sujendran Vijay , di Pietro Massimiliano 
Published: September 2024

Abstract

Background
Endoscopic resection (ER) is curative for Barrett’s oesophagus-related early-stage oesophageal adenocarcinoma (EAC) without high-risk features, such as lymphovascular invasion (LVI), positive margins (R1), and deep submucosal invasion (T1bsm2-3). Piecemeal endoscopic mucosal resection (pEMR), often used for lesions larger than 15mm, prevents assessment of lateral margins and therefore complicates precise risk estimation for residual EAC at the first post-ER endoscopy. Thus, we investigated alternative clinical factors that could potentially be used to assess the risk for residual and recurrent EAC post-ER.

Methods
We performed a longitudinal cohort study of patients who underwent ER between 2006-2023. Inclusion criteria were: T1a or well/moderately differentiated T1bsm1 EAC; LVI-, and R0 resection. ER was categorised as pEMR (n=106) or en-bloc ER (n=22 en-bloc EMR, n=9 endoscopic submucosal dissection). The primary outcome was residual EAC at first post-ER endoscopy. Secondary outcomes were residual HGD at first post-ER endoscopy, EAC and HGD recurrence at any post-ER endoscopy, and remission of EAC, HGD and intestinal metaplasia (IM) at latest endoscopy. Multivariate logistic regression, receiver operating characteristics, chi-squared, and Kaplan Meier analyses were performed to investigate possible associated risk factors.

Results
Rates of EAC/HGD recurrence were higher post-pEMR versus en-bloc ER (p=0.019), with residual EAC at first post-ER endoscopy accounting for 34% of post-pEMR recurrence. The percentage of pEMR specimens with EAC (p=0.022) and T1bsm1 staging (p=0.013) were independent risk factors for residual EAC at first post-pEMR endoscopy (Table 1). A 53.5% cut-off of involved pEMR specimens was identified as the optimal threshold for residual EAC prediction (specificity=0.68, sensitivity=0.67). Indeed, residual (p=0.012) and recurrent (p=0.00077) EAC rates were higher when EAC involvement was &gt;53.5%. However, rates of EAC (p=0.13), HGD (p=0.19) and IM (p=0.76) remission were unaffected by high EAC burden.

Conclusions
High burden of EAC on pEMR specimens correlates with increased risk of residual and recurrent EAC at post-pEMR endoscopy. Post-pEMR site check is recommended prior to endoscopic ablation, particularly in patients where more than 50% of pEMR specimens show EAC and in cases of flat subtle lesions. This will ensure eradication of any residual disease and high success rates for treatment of early EAC using endotherapy.
360. RECURRENCE PATTERNS AFTER PRIMARY SURGERY AND NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL ADENOCARCINOMA: ACROSS THE CROSS RECURRENCES
Authors: Bouckaert Andreas , Moons Johnny , Lerut Toni , Coosemans Willy , Depypere Lieven , Mandeville Yannick , Van Veer Hans , Nafteux Philippe 
Published: September 2024

Abstract

Background
Our publication Across the CROSS in daily practice challenged the routine use of neoadjuvant chemoradiotherapy for locally advanced esophageal adenocarcinoma, showing a comparable 5-year overall and disease-free survival after primary surgery. This current study reevaluated overall and disease-free survival on long term and aimed to differentiate recurrence patterns and its final impact on overall survival.

Methods
This retrospective cohort study with propensity score-matched analysis included all surgically treated patients between 2000 and 2018 with locally advanced adenocarcinoma (cT1/2N+ or cT3/4N0/+). Exclusion criteria of the CROSS trial were applied. Patients were matched on age, Charlson comorbidity score, clinical tumor length, and lymph node status. The primary end point was time to recurrence.

Results
149 propensity score-matched cases were defined in each group. There was still no significant difference after 10 years in median overall survival (33.6 vs 34.9 months, p=0.52) and median disease-free survival (14.1 vs 14.0 months, p=0.13) between both groups. Furthermore, nCRT resulted in a shorter time to overall recurrence (6.3 vs 11.5 months, p=0.004) and locoregional recurrence (6.3 vs 13.6 months, p=0.005). Additionally, overall survival after diagnosis of recurrence was also significantly shorter for nCRT patients than for primary surgery patients (6.9 vs 9.6 months, p=0.032).

Conclusion
Our propensity score-matched results indicate that primary surgery can offer a comparable long-term overall and disease-free survival as nCRT followed by surgery. Both overall and locoregional recurrences occur earlier in nCRT patients and overall survival after recurrence is significantly longer after primary surgery.
365. METHYLATION BIOMARKERS TO STRATIFY BARRETT’S ESOPHAGUS PATIENTS PROGRESSING AND NON-PROGRESSING TO ESOPHAGEAL ADENOCARCINOMA
Authors: Dehkordi Nastaran Riahi , Higareda-Almaraz Juan Carlos , Mancuso Francesco Mattia , Kruusmaa Kristi , Bertossi Arianna 
Published: September 2024

Abstract

Background
Over the last forty years, North America and Europe have witnessed a notable surge in cases of esophageal adenocarcinoma (EAC). This malignancy typically arises from Barrett esophagus (BE), a condition characterized by the replacement of normal squamous epithelium with specialized metaplastic cells. Our study aims to identify specific methylation markers capable of distinguishing between BE patients that will and will not progress to EAC.

Methods
We conducted differential expression analysis on RNASeq public dataset GSE210647 to distinguish BE progressors from non-progressors. Reads were aligned to hg38 genome using STAR aligner, normalized and analyzed with DESeq2. Significant genes were selected by |log2 fold change| ≥ 0.2 and padj &lt; 0.01. GO, pathway enrichment, and transcription factor (TF) network analyses were performed to uncover biological disparities. Integration with previous methylation data (N.R. Dehkordi et al., 292. Specific methylation markers associated with changes in gene expression distinguish EAC and sub-types of BE patients, ISDE 2023) allowed the identification of overlapping biomarkers, aiding in better discrimination between the two groups.

Results
Differential expression analysis of GSE210647 identified 2261 significative DEGs between BE progressors and non-progressors. Pathway enrichment analysis in BE progressors revealed significant associations with cellular morphogenesis and reprogramming, alongside the induction of the bile acid pathway, known for its implications in invasiveness and cancer stem cell expansion. TF network analysis identified key regulators such as TBX20, FOXS1, and ZNF454, shedding light on their roles in esophageal carcinogenesis.
Among the 505 CpG markers acquired in prior analyses, 127 genomic regions were linked with overexpressed genes either in progressors or in non-progressors BE patients. Leveraging this marker panel, BE samples were stratified into discrete subtypes, aligning either with normal esophageal tissue or EAC, and suggesting a potential stratification by disease progression.

Conclusions
The integration of expression and methylation analyses allows the identification of key genomic and epigenomic loci able to distinguish BE patients progressing or not-progressing towards EAC. The identified biomarkers are pivotal for personalized risk assessment and for the design of targeted interventions, holding promises for enhanced surveillance protocols, refined early EAC detection approaches, and improved therapeutic strategies aimed at mitigating the risk of EAC development in BE population.
366. MINIMALLY INVASIVE MANAGEMENT OF AORTO-OESOPHAGEAL FISTULA: THORACIC ENDOVASCULAR AORTIC REPAIR AND THORACOSCOPIC ASSISTED OESOPHAGECTOMY WITH DELAYED GASTRIC CONDUIT RECONSTRUCTION
Authors: Emanuwa Emudiaga , Weerakkody Ruwan , Falah Orwah , Couper Graeme 
Published: September 2024

Abstract

Background
Development of aorto-oesophageal fistula (AOF) within the context of thoracic aortic aneurysm is rare and carries a high mortality rate. Here we present two cases detailing the successful management of AOF.

Methods
A 58 year old male presented with haematemesis. CT angiogram demonstrated fistulation between a mycotic aneurysmal thoracic aorta and the oesophagus. He underwent Thoracic Endovascular Aneurysm Repair (TEVAR). This was followed by thoracoscopic assisted oesophagectomy (TAO) and delayed gastric conduit reconstruction.
A 49 year old female presented with massive haematemesis. CT angiogram demonstrated a calcified thoracic aneurysmal sac. This was managed with TEVAR. Subsequent investigations revealed mediastinitis, stent graft infection and AOF. This was managed with TAO and delayed gastric conduit reconstruction.

Results
Gastric conduit reconstruction achieved an excellent functional result in both patients. Ongoing Aortic CT surveillance has revealed satisfactory appearances with no current plans for further vascular intervention. Both patients have returned to full employment.

Conclusions
TEVAR should be used as the initial bridging intervention to stabilise haemodynamically unstable patients with AOF. Subsequent oesophageal resection can be safely performed using a minimally invasive approach with subsequent retro-sternal reconstruction using a gastric conduit. CT follow up demonstrate no ongoing issues with the implanted aortic stents
369. IMPACT OF THE COVID-19 PANDEMIC ON ESOPHAGEAL CANCER PATIENTS UNDERGOING ESOPHAGECTOMY: AN ACS-NSQIP DATABASE ANALYSIS
Authors: Chobarporn Thitiporn , Wood Stephanie 
Published: September 2024

Abstract

Background
To cope with the increasing number of infected patients, medical access was restricted, and public facilities were closed throughout the COVID-19 pandemic. Early detection and treatment of esophageal cancer is critical for improved prognosis. However, the impact of pandemic-related medical access restrictions has not be evaluated to date for esophageal cancer. Therefore, the purpose of this research is to determine how the lockdown policy affected the surgical outcome of patients with esophageal cancer.

Methods
We analyzed patients who underwent esophagectomy for esophageal cancer between 2016-2022 using data obtained from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), including the procedure targeted esophagectomy database. The patients were stratified into two groups based on their operation date relative to pandemic (BEFORE COVID group: 2016-2019 vs AFTER COVID group: 2020-2022). Demographic data and perioperative outcomes were compared between the two groups. Statistical analysis included Chi-square tests for categorical variables and independent student T-tests for continuous data, with a significance threshold set at p &lt; 0.05.

Results
Between 2016-2022, 7,198 esophageal cancer patients underwent esophagectomy. Clinical T4 increased significantly, but clinical N and pathologic T and N stages showed no impact. PET scan imaging, neoadjuvant chemotherapy and radiotherapy remained unchanged. The utilization of a minimally invasive approach rose substantially from 32.6% to 47.2% (p &lt; 0.001). Positive margin rates increased from 7.5% to 9% (p = 0.03), and anastomotic leak rates increased from 14.1% to 17.2% (p &lt; 0.001). Operative time, blood loss, and conversion rate showed no significant differences. Perioperative complications, including organ space surgical site infections and myocardial infarctions, significantly increased after COVID-19.

Conclusion
The COVID-19 pandemic altered the clinical staging of esophageal cancer patients undergoing esophagectomy, but it did not disrupt access to essential investigations and treatment. A notable increase in the implementation of minimally invasive techniques was observed after the pandemic. However, significant impacts were noticed on operative outcomes, including positive margin and leak rates.