bluuebunny/crossref_metadata_2025 huggingface dataset:
291. CLINICAL OUTCOMES OF IMMUNOCHEMOTHERAPY FOR UNRESECTABLE OR RECURRENT ESOPHAGEAL SQUAMOUS CELL CARCIONOMA
Authors: Nakajima Yasuaki , Ogiya Kazuo , Miura Shunsuke , Nakata Yutaka , Yamamoto Yudai , Iwata Noriko , Endo Haruhisa , Saeki Ichiro , Takahashi Sadao
Published: September 2024

Background/Aim

KEYNOTE-590 and CheckMate 648 study showed significantly feasible clinical outcomes in patients with advanced esophageal carcinoma. Herein, we report our clinical results of immunochemotherapy for unresectable and recurrent esophageal squamous cell carcinoma.

Patients and Methods

17 patients who received pembrolizumab plus 5-fluorouracil and cisplatin (IO+C) and 9 patients who received nivolumab plus ipilimumab (IO+IO) were enrolled.

Results

The median age of the IO+C group was 70 years, and all patients had unresectable disease. A median of 2 courses of treatment were performed, and the best overall response rate was 68.6% including CR in 2 patients, PR in 9 patients, SD in 4 patients, PD in 1 patient and NE in 1 patient. One-year progression-free survival rate (PFS) was 36.1% and one-year overall survival (OS) was 64.6%. Immune-related adverse events (irAE) included liver damage in 4 patients, skin damage in 4 patients, thyroid dysfunction in 2 patients and lung damage in 1 patient. The median age of the IO+IO group was 79 years, with 3 patients of unresectable disease and 6 patients of recurrence. A median of 2 courses of treatment were performed, and the best overall response rate was 71.4% including CR in 4 patients, PR in 1 patient, SD in 1 patient, PD in 1 patient, and NE in 2 patients. One-year PFS was 68.6% and one-year OS was 85.7%. irAE included liver damage in 3 patients, skin damage in 6 patients, thyroid dysfunction in 2 patients, rhabdomyolysis in 1 patient and hypopituitarism in 1 patient.

Discussion/Conclusion

Currently, in our institute, IO+C is the first choice for unresectable esophageal carcinoma, and IO+IO is selected for patients who are unresponsive or intolerant to FP, patients requiring outpatient treatment and patients with recurrent disease. Although long-term clinical outcomes will need to be examined, immunochemotherapy is very useful and it is necessary to examine the effective use of IO+C and IO+IO in the future.
295. SAFETY OF SURVEILLANCE GASTROSCOPY AND ENDOSCOPIC ULTRASONOGRAPHY IN THE OESOPHAGUS AFTER NEOADJUVANT CHEMORADIOTHERAPY: RESULTS FROM THE SANO COHORT
Authors: Gangaram Panday Sanjiv SG , Yean Low Kuan , Spaander Manon CW , Bisseling Tanya M , Curvers Wouter L , van Dieren Jolanda , Quispel Rutger , Oostenbrug Liekele , van der Linden Andries , Corporaal Sietske , Hol Lieke , Kouw Eva , van der Kraan Jolein , Hazen Wouter L , Honing Judith , van Lanschot Jan JB , Mostert Bianca , Nuyttens Joost J , Wijnhoven BasPL , van der Sluis Pieter C , Lagarde Sjoerd M
Published: September 2024

Background

An organ sparing strategy has been proposed for patients with oesophageal cancer and a clinically complete response after neoadjuvant chemoradiotherapy (nCRT). This active surveillance strategy involves (repeated) oesophagogastroduodenoscopy (OGD) with bite-on-bite biopsies and endoscopic ultrasonography (EUS). The preSANO trial and preliminary results of the SANO trial concluded that these procedures are safe to identify those with a clinically complete response. However, the safety of these procedures beyond that timeframe remains unknown. The aim of this study is to assess the safety of endoscopic procedures after nCRT, extending beyond three months.

Methods

This is a retrospective multicentre cohort study. All patients who participated in the pre-SANO and SANO studies were included. All were treated with CROSS nCRT for oesophageal cancer and underwent (repeated) endoscopic response evaluations (OGD with bite-on-bite biopsies and/or EUS with fine needle aspiration, as indicated). Primary outcome was serious adverse events (SAE) as defined by Central Committee on Research Involving Human Subjects (CCMO) associated with endoscopic procedures which include (but are not limited to) bleeding, infection and perforation. Secondary outcome included mechanical injury.

Results

A total of 919 patients underwent at least one endoscopic response evaluation. Some 2355 endoscopic procedures (61% OGD with EUS combined, 33% OGD and 6% EUS) were performed. Of these, 819 (35%) were performed more than three months after nCRT. SAEs were reported for five endoscopic procedures (0.2%) and included three cases of gastrointestinal bleeding after OGD with biopsies and two cases with infection secondary to the endoscopic procedures. No significant difference in SAEs was found between the procedures conducted before and more than three months after nCRT (2 vs. 3, OR 2.8, 95% CI, 0.3 – 33.7, P = 0.35).

Conclusion

OGD with biopsies and EUS are both procedures which can be safely performed after nCRT during an active surveillance strategy.
296. CLINICAL T1B-SM2-3N0M0 ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Iizuka Toshiro , Noma Eriko
Published: September 2024

Background

With advancements in endoscopic techniques, safer and more reliable endoscopic resection of submucosal invasive lesions has become feasible. The evaluation of treatment outcomes for superficial esophageal carcinoma has typically been predicated on the depth of pathological diagnosis; however, there have been limited studies based on preoperative diagnosis. Given that treatment decisions in clinical practice are primarily guided by preoperative diagnosis, there is a heightened emphasis on studies grounded in preoperative assessments. This study aims to analyze the accuracy of preoperative diagnosis of T1b-SM2-3 N0M0, evaluate the accuracy of treatment selection and depth diagnosis, and assess long-term outcomes based on these determinations.

Methods

Thirty-eight patients diagnosed with T1b-SM2-3 N0M0 between April 2010 and December 2020 were included in the study. Depth diagnosis was determined through endoscopic evaluation utilizing white light, NBI, NBI magnification plus EUS, with lymph node metastasis diagnosis performed via CT imaging. Treatment decisions were made following patient consent, and long-term prognosis was assessed for each treatment modality.

Results

Initial treatment involved ESD in 14 patients, with an additional 5 patients undergoing additional treatment (ESD + AD) based on histological evaluation (surgery: 1, CRT: 4). Surgery or neoadjuvant chemotherapy (NAC) followed by surgery was performed in 15 patients, with CRT administered in 7. Among the 22 patients who did not receive NAC and whose histologic depth was evaluable, the accuracy rate of depth diagnosis was 64%, primarily attributable to overdiagnosis. In the 14 patients who underwent ESD excluding piecemeal resection, the negative rate of vertical margins was 93%. Five-year overall survival rates were as follows: ESD: 64.8%, ESD+AD: 75%, surgery: 86.2%, and CRT: 45.7%, with no statistically significant differences observed. The majority of deaths (83%) were attributed to other diseases or cancers, with only 2 deaths attributed to the primary disease.

Conclusion

ESD or surgery emerged as the preferred treatment modalities in the majority of cases, with relatively favorable long-term prognoses. Treatment decisions were influenced by comorbidities and other factors, potentially impacting long-term outcomes.
297. ASSESSING BLOOD-BASED BIOMARKERS IN OESOPHAGEAL CANCER PATIENTS RECEIVING NEOADJUVANT CHEMORADIOTHERAPY
Authors: Al Azzawi Mohammed , O’Reilly D , Hill A , Crown J , Collins DM , Robb WB
Published: September 2024

Background

Oesophageal cancer is the sixth most common cause of cancer-related deaths globally. It has a significant rate of mortality despite the multimodal approach to treatment. Neo-adjuvant chemoradiotherapy is standard of care but there is a clinical need for new therapies. HER2-targeted therapies and immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have emerged as treatment strategies of significant interest in recent years. This study focuses on exploring potential plasma-based biomarkers (growth factors, cytokines, soluble (s) PD-L1) in patients (pts) with oesophageal cancer receiving standard of care neo-adjuvant therapy and stratified based on HER2 expression and pathological complete response (pCR).

Methods

50 pts with oesophageal cancer who are eligible for neoadjuvant therapy were recruited. Blood samples were taken pre-treatment, on the first day of the 2nd cycle and post-neoadjuvant treatment. Plasma was extracted within four hours of blood draw and stored at -800C. 20 matched pre- and post-treatment samples were included in this analysis. HER2 status (IHC 3+ (n=3), IHC 2+ (n=5), IHC 1+ (n=3), IHC 0 (n=6) was available for 17 pts. 3 pts achieved a pCR but no HER2 IHC data was available. The levels (pg/ml) of 21 analytes were assessed using the Human Growth Factor Luminex Performance Assay and a Luminex MagPix system. Changes were significant if p<0.05, paired student’s t test.

Results

Twenty-one biomarkers of response were assessed in the final analysis. Platelet-derived growth factor (PDGF)-AA and PDGF AA/BB displayed the highest concentration levels of the tested analytes but levels did not change pre-and post-treatment. GRO-b (CXCL2) and vascular endothelial growth factor (VEGF) displayed a numerical increase post-treatment but this did not prove significant (p<0.05). Tumour-necrosis factor-related apoptosis-inducing ligand (TRAIL) protein decreased significantly post-therapy (p=0.038). PD-L1 levels significantly increased in the post-treatment cycles (paired t-test p=0.0029), especially in pts with HER2+ status. TRAIL or sPD-L1 levels were not significantly different when categorised by HER2 IHC or pCR status.

Conclusion

The increase in sPD-L1 and reduction in TRAIL levels in the peripheral blood of oesophageal cancer patients following neoadjuvant therapy suggests treatment alters factors associated with immune-suppression and the induction of tumour cell death. Further investigation in a larger cohort is warranted.
306. TREATMENT OF ANASTOMOTIC LEAKS AFTER ESOPHAGECTOMY AND GASTRECTOMY FOR CANCER BY MEANS OF ENDOSCOPIC VACUUM THERAPY
Authors: Turrado-Rodriguez Victor , Sendino Oriol , Piulachs Jordi Farguell , Garcia Anna Curell , Olanl Ainitze Ibarzabal , Pera Miguel , Garcia Dulce Momblan
Published: September 2024

Background

Esophagectomy and gastrectomy are the cornerstones of the curative treatment of oesophageal and gastric cancer. In both techniques the risk of anastomotic leak (AL) is high, with rates of up to 21% after esophagectomy and up to 12% after gastrectomy. Mortality and morbidity are high after an AL occurs. Several treatment strategies have been developed for treatment of AL, including surgery, endoscopic stent and endoscopic vacuum therapy (EVT). The aim of this study is to analyse the treatment patterns of the patients with AL treated with EVT.

Methods

All patients diagnosed of gastric or oesophageal cancer with AL from January 2021 to January 2024 were included in a retrospective study. Baseline data, localization of the tumour, type of resection, type of anastomosis, total time with EVT, number of EVTs used per patient, hospital stay, Clavien-Dindo score and CCI were recorded. A descriptive analysis of the data is performed.

Results

All 18 patients with AL during the study period were treated with EVT. The tumour was located on the distal third of the oesophagus in 7 patients (38.9%), and stomach (27.8%). The median duration from surgery to the identification of AL was 5 days (IQR 4 – 9). The median duration of the EVT treatment was 18 days (IQR 13 – 23) with a median EVT replacement of 5.5 (IQR 4 – 7). 8 patients (44.4%) did not require ICU stay. Median time to resumption of oral intake was 34 days (IQR 26 –54). Success rate of the EVT therapy was 88.9%.

Conclusions

EVT is a useful tool for the treatment of AL in esophagogastric surgery. Even though the treatment may be long, it’s success rate in this series is 88.9% and it may avoid ICU stay in some cases. A close monitoring of this patients and the prompt use of additional techniques to assure source control is mandatory.
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

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>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<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

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<0.001) and LOS (11 vs 4days, P<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 <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

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

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

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 >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

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

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 < 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

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

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 < 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 < 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 < 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.
384. NEOADJUVANT ANLOTINIB COMBINED WITH PENPULIMAB FOR RESECTABLE LOCALLY ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC): A PROSPECTIVE, SINGLE-ARM, PHASE II TRIAL
Authors: Yang YuShang , Liu Yixin , Chen Yueyun , Chen Longqi
Published: September 2024

Background

Neoadjuvant chemoradiation therapy followed by radical surgery has been extensively recommended for locally advanced esophageal squamous cell carcinoma (ESCC). However, toxicities and challenges to the subsequent surgery limit its wide clinical application. Immune checkpoint inhibitors combined with antiangiogenesis have synergistic effects and have shown good therapeutic effects in previous studies, as well as fewer side effects. Here, we tested a novel combination of anlotinib (an antiangiogeneic kinase inhibitor) and penpulimab (an anti-PD-1 antibody), without the use of radio- or chemo-therapy, for the neoadjuvant therapy of locally advanced ESCC.

Methods

In this prospective, single-arm, phase II clinical trial (ChiCTR2200064848), patients with resectable locally advanced ESCC (clinical stage III-IVa) were recruited. The study was designed using a two-stage minimax approach. The planned sample size was 40 patients would provide 80% power at a one-sided alpha error of 5%, threshold pathological complete response (pCR) of 16% and expected pCR of 30%. Here, the first-stage data was included. Notably, 85% (22/25) enrolled patients had medical contraindications (including cardiopulmonary diseases or other underlying medical conditions, along with poor nutritional status and so on). Patients received neoadjuvant therapy with anlotinib (8 mg, po, D1-14, Q3W) combined with penpulimab (200 mg, ivgtt, Q3W) for 2 cycles. Six to eight weeks later, patients underwent radical surgery after exclusion of contraindications. The primary endpoint was pathologic complete response (pCR) rate. Secondary endpoints included tumor regression grade (TRG), R0 resection rate, objective response rate (ORR) and safety profile.

Results

From Jan 2023 to Sep 2023, 25 patients (19 males and 6 females) were enrolled with a median age of 67 years (range: 50-74). All patients were available for efficacy assessment and 16 were evaluable for the primary end point. The rest of the patients are waiting for surgery. As of 15 Sep, 2023, 19 patients underwent esophagectomy and R0 resection rate was 87.5%. The pCR rate was 18.8% (3/16) and 31.3% of patients had a major pathologic response (MPR). The ORR and DCR were 48.0% and 96.0%, respectively. 84.0% of patients experienced grade 1-2 treatment-related adverse events (TRAEs), 3 (12.0%) patients experienced grade 3 TRAEs (2 elevated blood pressure and 1 elevation of liver enzymes). The safety profile revealed that the most common TRAEs (≥10%) included hypertension (28.0%), hand-foot syndrome (20%), fatigue (20%), abdominal pain (12%), toothache (12%).

Conclusions

The preliminary results of this study show promising safety and efficacy of anlotinib combined with penpulimab as neoadjuvant for patients with ESCC, especially for patients not suitable for neoadjuvant chemoradiation or chemotherapy. More ESCC patients would be recruited in the future.
387. VALIDATION OF PROMARKERESO, A DIAGNOSTIC BLOOD TEST TO IDENTIFY ESOPHAGEAL ADENOCARCINOMA
Authors: Peters Kirsten , Bringans Scott , Wang Iris , Duong Marisa N , Dhamrait Gursimran , Lipscombe Richard J
Published: September 2024

Background

Esophageal adenocarcinoma (EAC) has become the predominant type of esophageal cancer in Western countries. Early diagnosis and intervention of EAC significantly reduces the disease mortality. A previous study identified a panel of novel serum glycoprotein biomarkers that were associated with EAC, enabling the development of a prototype diagnostic blood test, PromarkerEso. The current study aimed to validate PromarkerEso in an independent cohort of patients with EAC.

Methods

Blood samples from an independent cohort of 165 participants (n=99 negative controls, n=66 diagnosed with EAC) were analyzed. Five candidate biomarkers were measured after lectin pulldown using a targeted mass spectrometry assay. Model performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC) with sensitivity and specificity determined.

Results

After adjusting for clinical variables, diagnostic models showed good discrimination to distinguish participants with EAC from negative control participants.

Conclusions

This study validates a panel of serum glycoprotein biomarkers for the diagnosis of EAC. These biomarkers have potential utility as a simple blood test, PromarkerEso, that could be used for screening EAC in a large population.
390. CONTINUED IMPLICATIONS OF THE COVID-19 PANDEMIC ENVIRONMENT ON ESOPHAGEAL CANCER CHARACTERISTICS AND TREATMENT IN THE UNITED STATES
Authors: Stuart Christina , Bronsert Michael , Mott Nicole , Rodriguez-Franco Salvador , Gleisner Ana , Mungo Benedetto , Randhawa Simran , David Elizabeth , Mitchell John , McCarter Martin , Meguid Robert
Published: September 2024

Background

The COVID-19 pandemic significantly impacted the stage of presentation and subsequent therapies for patients who were diagnosed with esophageal cancer during the first pandemic year. We aimed to assess for continued implications of the altered healthcare landscape on esophageal cancer presentation and treatment in the second year of the pandemic.

Methods

This was a retrospective review of the United States National Cancer Database (2019-2021). Demographic, cancer-related and treatment variables were compared between patients diagnosed in the pre-pandemic year (2019), pandemic year one (2020) and pandemic year two (2021). Multivariate logistic regression was performed to control for the impact of demographics on oncologic variables, and then for the impact of oncologic variables on treatment modalities and outcomes.

Results

Of 42,807 esophageal cancer cases, 15,127 (35.3%) were pre-pandemic, 13,975 (32.7%) were pandemic year 1, and 13,705 (32.0%) were pandemic year two. There were significant differences in the distribution of clinical stage at presentation by year (p=0.0001), see figure, suggesting more advanced stage presentation throughout the pandemic. Compared to the pre-pandemic year, patients diagnosed in pandemic year two had risk-adjusted increases in time to first course treatment (incidence rate ratio 1.057 [95% confidence interval [1.036–1.078]), to radiation (1.029 [1.008–1.050]), and to systemic therapy (1.035 [1.018–1.051]). Additionally, when compared to pandemic year one, patients in pandemic year two continued to experience risk-adjusted increases in time to first course therapy (1.084 [1.063–1.106]), to surgery (1.049 [1.000–1.097]), to radiation (1.046 [1.024–1.068]) and to systemic therapy (1.060 [1.043–1.077]).

Conclusions

Compared to the pre-pandemic year, patients diagnosed with esophageal cancer in in the U.S. during pandemic year two continued to experience delays to treatment including delays to first course therapy, including delays to surgery, radiation and systemic therapy. The treatment characteristics of esophageal cancer have not returned to pre-pandemic baseline in the United States possibly due to compounding delays to diagnosis and treatment and a growing back log of cases.
403. ROBOTIC-ASSISTED IVOR LEWIS ESOPHAGECTOMY COMPARED TO CONVENTIONAL MINIMALLY INVASIVE ESOPHAGECTOMY: RESULTS FROM SEVEN HIGH VOLUME ITALIAN CENTERS
Authors: Voltarel Guerrino , Turolo Cecilia , Collizzolli Alice , Canepari Elia , Ajazi Barbara , De Pasqual Carlo Alberto , Weindelmayer Jacopo , Giacopuzzi Simone
Published: September 2024

Background

Over the past decade, minimally invasive esophagectomy has gained increasing attention, supported by numerous trials and retrospective series highlighting its advantages over the traditional open approach. In addition to the conventional minimally invasive surgery (CMIE), robotic assisted minimally invasive esophagectomy (RAMIE) has gained global popularity, due to its advantages in terms of 3D visualization and instrument stability.

Methods

This is a collaborative study involving seven high-volume Italian centers affiliated with the Italian Society for the Study of Esophageal Diseases (SISME). Patients who underwent Ivor Lewis esophagectomy for esophageal cancer between January 2015 and July 2022 were identified from seven institutional databases and divided in two groups according to the thoracic approach: CMIE versus RAMIE.

Results

We identified 316 patients in CMIE and 123 in RAMIE group. Operative time was significantly longer for RAMIE procedures (p<0.001). A borderline significant reduction in overall complication rate was observed (48% vs 59% in CMIE group, p=0.045), however there were no differences in severe (p=0.3) and pulmonary (p=0.13) complications rate. 90-day mortality (CMIE 3.2% vs RAMIE 0.8%, p=0.15) and readmission rate (CMIE 9.5% vs RAMIE 7.3%, p=0.47) were comparable. R0 rate was 94.9% in CMIE vs 92.7% in RAMIE (p=0.4). The most performed anastomosis was circular stapled anastomosis. Anastomotic leak rate was 13.9% for CMIE and 12.2% for RAMIE (p=0.6).

Conclusion

Minimally invasive Ivor Lewis esophagectomy has reached adequate surgical and oncological results with both conventional and robotic technique. Nowadays there is no clear superiority of one anastomotic technique.
404. REAL-WORLD TREATMENT PATTERN OF EOSINOPHILIC ESOPHAGITIS IN JAPAN
Authors: Sawada Akinari , Ihara Yasutaka , Imai Takumi , Fujiwara Yasuhiro
Published: September 2024

Background

Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration in the esophageal epithelium that causes esophageal dysfunction-related symptoms. The treatment for EoE includes acid suppressants (proton pump inhibitors (PPIs) or potassium competitive acid blocker (P-CAB)), topical corticosteroid (TCS), and diet therapy. In addition, biologics (i.e. dupilumab) have been recently approved for EoE in the US. However, the appropriate initial and maintenance therapy for EoE have not been established yet. Therefore, the aim of the study was to investigate the treatment pattern of EoE and its association with fibrostenosis in Japan.

Methods

We investigated prescription pattern for EoE analyzing an employer-based health insurance claim database from 2005 to 2022. EoE cases were identified based on the International Classification of Diseases-tenth Revision code, K20.0. The initial treatment of interest for EoE included PPIs, P-CAB, and TCS (swallowed inhaled CS). The initial treatment for EoE was defined as these drugs prescribed within two months from the index date of EoE diagnosis. The discontinuation rates of initial PPIs or P-CAB were analyzed using Kaplan-Meier method. The discontinuation of treatment was defined as no treatment following within 90 days from the prescription of the previous treatment.

Results

Overall, 984 EoE patients (45 years old [38-52], male 747 [75.9%]) were ultimately analyzed. Most of the initial treatment for EoE was acid suppressants (PPIs [323 54.9%], P-CAB [241, 41%]), followed by TCS (13, 2.2%) and combination therapy of PPIs or P-CAB and TCS (11, 1.9%). PPIs or P-CAB discontinued in approximately 50% and 70% of the cases at approximately 150 days and 720 days respectively from the start of the initial therapy. The switching to the second-line therapy from the initial PPIs or P-CAB rarely happened. During the observation period, no EoE patients developed esophageal stenosis.

Conclusion

PPIs or P-CAB were most prescribed as the initial treatment for EoE in Japan. In addition, more than half of EoE patients discontinued such initial therapy within 2 years without fibrostenotic complication. These findings indicate that EoE that can respond to initial acid suppressants therapy does not necessarily require the maintenance therapy to prevent esophageal fibrostenosis.