bluuebunny/crossref_metadata_2025_split huggingface dataset:
221. INTERVAL METASTASES AFTER NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED ESOPHAGEAL CANCER: A MULTICENTER OBSERVATIONAL COHORT STUDY
Authors: Zijden Charlène , Sluis Pieter , Mostert Bianca , Nuyttens Joost , Lanschot Jan , Spaander Manon , Valkema Roelf , Coene Peter-Paul , Dekker Jan-Willem , Fiets Willem , Hartgrink Hendrik , Hazen Wouter , Kouwenhoven Ewout , Nieuwenhuijzen Grard , Rosman Camiel , Sandick Johanna , Sosef Meindert , Zaag Edwin , Lagarde Sjoerd , Wijnhoven Bas 
Published: August 2023

Abstract

Background
Despite trimodality treatment, 10–20% of patients with esophageal cancer develop metastases after surgery. Re-staging after neoadjuvant chemoradiotherapy (nCRT) may be useful to identify these patients who should not have proceeded to surgery. In this multicenter observational cohort study, we assessed the proportion of patients with interval metastases after nCRT. Secondary outcomes were overall survival (OS), location and treatment of metastases.

Methods
Between 2013–2021, patients with cT2-4aN0–3 M0 esophageal/junctional cancer who underwent nCRT were identified from three prospective study-databases. Re-staging with 18F-FDG-PET/CT ≤14 weeks after completion of nCRT was performed in all patients. Metastases detected on imaging or during surgery were categorized into oligometastatic (≤3 lesions located in one single organ or in one extra-regional lymph node station) or non-oligometastatic. Treatment of metastases was based on pretreatment multidisciplinary tumor board reports for patients with oligometastatic disease and consisted of systemic therapy, loco(regional) therapy or best supportive care. OS was calculated from completion of nCRT until date of death or last day of follow-up.

Results
Metastases were detected in 100 of 973 patients (10.3%). The majority (84%) were detected by 18F-FDG-PET/CT and in 16% during surgery of which 60% were peritoneal metastases. Oligometastatic disease was seen in 30% of patients and 12 patients (40%) were treated with potentially curative intent. Median OS of patients with oligometastatic disease who were treated with potentially curative intent was 22.8 months (95% CI 10.4-NA), compared to 13.8 months (95% CI 9.2–27.1) in patients treated with palliative intent. Oligometastases were mostly located in non-regional lymph nodes (33.3%) or bones (26.7%). Median OS non-oligometastatic disease 9.0 months (95% CI 7.4–10.9).

Conclusion
Interval metastases were detected in about 10% of esophageal cancer patients after nCRT and the majority had non-oligometastatic disease. This underlines the benefit of restaging to select patients who are not candidates for esophagectomy. Treatment of oligometastases might lead to favorable survival in selected patients.
223. UNDERSTANDING POTENTIALLY PREVENTABLE MORTALITY FOLLOWING ESOPHAGO-GASTRIC CANCER SURGERY: ANALYSIS OF A NATIONAL AUDIT OF SURGICAL MORTALITY
Authors: Liu David , Fayed Aly , Evans Penelope , Bright Tim , Aly Ahmad , Duong Cuong , Spillane John , Weinberg Laurence , Watson David 
Published: August 2023

Abstract

Introduction
At a national level, understanding preventable mortality after esophago-gastric cancer surgery can direct quality-improvement efforts. Here, we utilized the Australian and New Zealand Audit of Surgical Mortality (ANZASM) database to 1) determine the causes of death following esophago-gastric cancer resections in Australia, 2) quantify the proportion of potentially preventable death, and 3) identify clinical management issues contributing to preventable mortality.

Methods
All in-hospital mortalities following esophago-gastric cancer surgery from 01/01/2010 to 31/12/2020 were analyzed from ANZASM data. Potentially preventable and non-preventable cases were compared. Thematic analysis was used classify clinical management issues. Overall, we reviewed 636 complications and 123 clinical management issues in 105 mortalities.

Results
The most common causes of death were cardio-respiratory in etiology. Forty-nine (46.7%) mortalities were potentially preventable. These cases were characterized by higher rates of sepsis (59.2% vs. 33.9%, p = 0.011), multiorgan dysfunction syndrome (40.8% vs. 25.0%, p = 0.042), reoperation (63.3% vs. 41.1%, p = 0.031), and other complications compared with non-preventable mortality. Potentially preventable mortalities also had more clinical management issues per patient [median (IQR): 2 (1–3) vs. 0 (0–1), p &lt; 0.001), which adversely impacted preoperative (30.6% vs. 7.1%, p = 0.002), intraoperative (18.4% vs. 5.4%, p = 0.037), and postoperative (51.0% vs. 17.9%, p &lt; 0.001) care. Thematic analysis highlighted recurrent areas of deficiency in patient management.

Conclusions
Almost 50% of deaths following esophago-gastric cancer resections were potentially preventable. These were characterized by higher complication rates and clinical management issues. We highlighted recurrent themes in patient management to improve future quality-of-care.
228. THORACOACROMIAL ARTERY PERFORATOR FLAP REPAIR OF ACQUIRED INTRATHORACIC NONMALIGNANT TRACHEOESOPHAGEAL FISTULAS THROUGH A MIDSTERNAL INCISION APPROACH
Authors: Yuan Pei-song , Wu Na , Xia Qi , Hu Yang 
Published: August 2023

Abstract

Background
Acquired intrathoracic nonmalignant tracheoesophageal fistulas (TEFs) are rare and challenging surgical problems. They can constitute a life-threatening condition due to severe pulmonary complications and poor nutrition. The current treatment strategy for TEFs is controversial, and postoperative mortality and complication morbidity have been ignored in recent studies. Here, we introduce our innovative experience repairing acquired tracheoesophageal fistulas with a thoracoacromial artery perforator flap, in which no mortality or complications were observed within 180 days after the operation.

Methods
Surgical repair with a thoracoacromial artery perforator flap through a midsternal incision approach was performed in 3 patients. During the procedure, a midsternal incision was made. After the thymus and anterior mediastinal fat were resected, and the left innominate vein was transected, the trachea and esophagus were mobilized. The trachea was incised and pulled to the cranial and caudal sides. Then, the thoracoacromial artery perforator flap was harvested and transferred into the superior mediastinum for esophageal reconstruction. Subsequently, the trachea was anastomosed end to end after debridement, and the left innominate vein was either anastomosed or not.

Results
Two patients developed esophageal anastomotic leakage postoperatively and healed well after nonsurgical treatment. No mortality or other complications were observed at 180 days after the operation.

Conclusion
Repair of acquired tracheoesophageal fistulas using a thoracoacromial artery perforator flap through a midsternal incision approach is an effective, safe surgical treatment.
246. SPATIAL HETEROGENEITY OF PD-L1 EXPRESSION INFLUENCE ITS ASSESSMENT IN ESOPHAGEAL SQUAMOUS CARCINOMA (ESCC)
Authors: Yu Boyao , Liu Zhichao , Ma Ning , Pan Jie , Li Zhigang 
Published: August 2023

Abstract

Background
Anti-PD-1/PD-L1 immunotherapy is a promising treatment for ESCC. High PD-L1 expression is a theoretical predictive biomarker, but the poor response is also observed in some patients with high PD-L1 expression. Biopsies assessment of PD-L1 expression always focuses on a single region which may be influenced by spatial heterogeneity of tumor microenvironment. This study investigates whether the PD-L1 expression by biopsy assessment in the different spatial regions is related to its paradoxical predictive value.

Methods
We prospectively included 30 consecutive patients with treatment-naïve, stage II-III ESCC who underwent upfront esophagectomy. Multi-region sampling was taken with endoscopic biopsy forceps (Fig. A) from four regions (A/B/C/D) from the proximal, distal, midpoint of tumor surface, and internal center, respectively. Each region was spaced ≥1 cm apart and avoided areas of severe necrosis. We compared the PD-L1 expression at different endoscopic-biopsy regions and the overall surgical-resected tumor specimen. PD-L1 expression was evaluated by immunohistochemistry using combined positive score (CPS). PD-L1 expression positive and negative is defined as CPS ≥ 1 and CPS &lt; 1, respectively.

Results
Based on surgical-resected tumor, PD-L1 positive and high were 66.7% and 10% of 30 patients, respectively. PD-L1 positive/negative discordance rate of four sampling regions was 66.7% with poor concordance (kappa = 0.206) (Fig. B). Correlations between four biopsy regions of PD-L1 expression (Fig. C) revealed high in B and D (r = 0.77) but relatively low in others. Combining multi-region sampling for evaluation improved the correlation consistency of PD-L1 expression assessment (Fig. D). Comparing PD-L1 expression based on the endoscopic-biopsy region with the gold standard surgical-resected specimen, the sensitivity was increased by 12.5% for multi-region versus single-region assessment.

Conclusion
PD-L1 expression was spatially heterogeneous in ESCC, and a single region cannot reflect the PD-L1 status of the tumor, consistent with the observation of suboptimal prediction of PD-L1 expression for ESCC immunotherapy. Multi-region biopsy could help improve the assessment bias of PD-L1 expression related to spatial heterogeneity, and may help to improve the identification of the candidate for immunotherapy.
255. EARLY COST-EFFECTIVENESS MODELLING STUDY COMPARING MINIMALLY INVASIVE TRANSCERVICAL ESOPHAGECTOMY (MICE) AND TRANSTHORACIC MINIMALLY INVASIVE ESOPHAGECTOMY (TMIE) IN OESOPHAGEAL CANCER PATIENTS
Authors: Klarenbeek Bastiaan , Leijten Lars , Scholte Mirre , Veenendaal Linde , Rovers Maroeska , Rosman Camiel 
Published: August 2023

Abstract

Introduction
Minimally Invasive transCervical Esophagectomy (MICE) is a novel transcervical approach to esophagectomy with the possible advantage of decreased pulmonary complications. MICE is in an early stage of introduction in patients which are treated with the McKeown procedure in regular practice. The aim of this study was to provide insight in the potential cost-effectiveness of MICE and its sensitivity to different complications.

Methods
A decision tree modelled the postoperative outcomes of recurrent laryngeal nerve paresis, anastomotic leakage, pulmonary complications and 30-day mortality. Subsequently, we developed a Markov state transition model to calculate the effects of these input parameters on health outcomes (QALYs) and costs. The results were analysed with a sensitivity analysis and a scenario analysis of a clinical trial of a similar procedure.

Results
Preventing complications seemed to be effective in reducing hospital costs, but resulted in a limited improvement of health outcomes. Improving 30-day survival demonstrated to have a larger effect on health outcomes. A scenario analysis of data from a clinical trial studying similar procedures resulted in a cost reduction of €2974 and an increase of 0.016 QALYs per patient.

Conclusion
Reduced healthcare costs and improved health outcomes from reducing complications and 30-day mortality could offset the increased cost of MICE and lead to a cost-effective innovation. We advise close monitoring of short and long term survival outcomes in future studies.
268. DEVELOPMENT OF A NOVEL ESOPHAGUS-ON-A-CHIP MODEL: A HIGH-FIDELITY PLATFORM FOR DIRECTING PERSONALIZED THERAPY IN ESOPHAGEAL ADENOCARCINOMA
Authors: Pal Sanjima , Shimshoni Elee , Flores-Torres Salvador , Bérubé Julie , Kong Mingyang , Giannias Betty , Hall Sean , Bertos Nicholas , Sangwan Veena , Ingber Donald , Ferri Lorenzo 
Published: August 2023

Abstract

Background
80% of patients diagnosed with esophageal adenocarcinoma (EAC) die of disease. Current standard of care for EAC is systemic cytotoxic, platinum-based neoadjuvant chemotherapy followed by resection and additional rounds of chemotherapy. Locally advanced, resectable patients often fail to respond due to intrinsic and/or acquired chemoresistance. Traditional preclinical models fail to offer alternative salvage options. To our knowledge, this is the first high-fidelity dynamic 3D platform implemented to study esophageal function, pathophysiology, and drug effects.

Methods
Primary tissues obtained from EAC patients at diagnostic biopsy were propagated into patient-derived organoids (PDOs). The upper (mucosal) channel of the esophagus-chip was designated for PDO-derived epithelial cells, while the lower stromal channel was designated for matched fibroblasts. Autologous cell types were exposed to a physiologically relevant flow of nutrient media and microtissues were formed. Epithelial permeability was determined by cascade blue assay. Using this model, a clinically relevant chemotherapy protocol was administered to study patient-specific tumor response. To determine microtissue development and cellular fate in response to chemotherapy, level of several epithelial/mesenchymal biomarkers were evaluated.

Results
Study cohort consisted of both chemo-sensitive and -resistant EAC patients. Esophagus-chip models were developed with samples from patient-matched tumor and normal tissue. Chips recapitulated morphological and histological features of their parental tissues. Epithelial barrier integrity was established within 5 days on-chip. Scanning electron microscopy revealed the presence of pleomorphic cells and mature microvilli in EAC-chips. In vitro administration of docetaxel triplet chemotherapy demonstrated efficacy similar to that observed in the clinical setting when assessed directly or indirectly. Confocal imaging revealed treatment-associated differential expression of epithelial (CK7, CK19), and mesenchymal (vimentin) markers.

Conclusion
3D-organoids conserve cellular heterogeneity of source patients, whereas esophagus-on-chip expand on this diversity by adding microphysiological relevance, stromal influence & flexible complexity. This high-fidelity biomimetic platform enables clinical mimicry and can predict patient-specific chemosensitivity within a clinically relevant timeframe. This esophagus-chip system is a promising potential replacement for both inefficient preclinical animal models and existing tumor-only avatars lacking stromal and microphysiological context.
303. THE TISSUE SYSTEMS PATHOLOGY-9 TEST PROVIDES CLINICALLY-IMPACTFUL RISK STRATIFICATION IN PATIENTS WITH BARRETT’S ESOPHAGUS: CLINICAL EXPERIENCE IN A MULTICENTER COHORT
Authors: Villa Nicolas A , Ordonez-Castellanos Miguel , Yodice Michael , Smolko Christian , Arora Meenakshi , Critchley-Thorne Rebecca J , Khara Harshit S , Diehl David L 
Published: August 2023

Abstract

Background
Barrett’s esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Society guidelines recommend surveillance of BE by endoscopy with biopsies with the goal of detecting dysplasia and EAC at early, treatable stages. However, current practices have limited ability to predict which patients with BE will progress to EAC. This study evaluated the use of the validated, commercially-available tissue systems pathology test (TissueCypher, TSP-9) to risk-stratify BE patients in a large clinical practice cohort.

Methods
TSP-9 test results ordered by 475 physicians from June 2016 to January 2023 for 3935 patients with BE with clinicopathologic data were analyzed. The test orders were from private practices and integrated healthcare systems (92.8%) and academic medical centers (7.2%). Submitted diagnoses were non-dysplastic BE (NDBE, n = 3553, 90.3%), indefinite for dysplasia (IND, n = 190, 4.8%), low-grade dysplasia (LGD, n = 112, 2.8%), or other (BE with sub-category not clearly specified, n = 80, 2.0%). The TSP-9 results (risk classes of low-, intermediate- or high-risk and predicted probability of progression to HGD/EAC within 5 years) were evaluated in all patients.

Results
The TSP-9 test scored 3267 (83.0%), 377 (9.6%), and 291 (7.4%) low-, intermediate- and high-risk, respectively. The TSP-9 test identified risk for progression in NDBE, IND, and LGD subsets, in males and females, and in patients with short- and long-segment BE (Fig. 1). The test scored 15.2% of NDBE patients as intermediate or high-risk. Patients with NDBE who received TSP-9 intermediate- and high-risk scores had predicted 5-year risk of progression to HGD/EAC of 8.1% and 16.2%, respectively, which are higher than progression rates in BE patients with LGD (6.7% in 5 years) for whom guidelines recommend endoscopic eradication therapy.

Conclusions
TSP-9 risk-stratified for progression independently of clinicopathologic features in a cohort of 3935 BE patients. The majority of BE patients scored low-risk, providing support for surveillance-only management. The test identified 15.2% of NDBE patients as intermediate/high-risk for progression, indicating that the test can enable early detection of patients who will benefit from escalation of care to prevent EAC. The TSP-9 test provides objective results to enable risk-aligned management to improve health outcomes for BE patients.
346. IMPACT OF VIRTUAL POST-OPERATIVE CARE ON ESOPHAGECTOMY PATIENTS DURING THE COVID-19 PANDEMIC
Authors: Xiao Karren , Bolger Jarlath , Ristic Ivan , Darling Gail , Yeung Jonathan 
Published: August 2023

Abstract

Background
The SARS-CoV-2 pandemic has resulted in disruptions to oncology practices amongst healthcare institutions globally. To adapt, telehealth has been increasingly implemented into oncologic care, including that of esophageal cancer patients, which has been met with overall success. However, there remains a lack of evidence in the literature pertaining to the outcomes of virtual postoperative appointments for esophagectomy patients.

Methods
We conducted a retrospective cohort study to assess the clinical outcomes of esophageal cancer patients attending phone call follow-up (virtual) visits compared to standard in person care after esophagectomy. Demographic data, clinical and disease characteristics, and hospital visit data within 6 months of operation were collected. This included surgical clinic visits, endoscopies, and emergency room (ER) admissions.

Results
168 esophagectomy patients underwent follow-up care between March 2020 to May 2022; 70 virtual and 98 in-person. Patients attending virtual appointments had significantly fewer ED admissions (−0.48, p = 0.005*, 95%CI [−0.80, −0.14]). Number of endoscopy visits (0.36, p = 0.110, 95%CI [−0.08, 0980]) and the number of clinic visits (0.42, p = 0.118, 95%CI [−0.11, 0.93]) were similar between the two cohorts. ER visits for virtual cohort included feeding tube complications (20.0%), dysphagia (20.0%), and abdominal pain (13.3%). For the in-person cohort, feeding tube complications (12.8%) and chest pain or cardiac features (9.3%) were the most common reasons.

Conclusion
The results of this study provide evidence for the increased use of telehealth following esophagectomy. The reduction in emergency admissions in the virtual cohort may be due to increased comfort with phone call appointments or increased fear of hospital visitation during the pandemic.
351. INVESTIGATING THE IMPACT OF INDUCTION CHEMOTHERAPY FOR ESOPHAGEAL ADENOCARCINOMA ON THE GUT MICROBIOME
Authors: Aiyar Niharikaa , Allen Jonathan , Akhter Akhi , Rispoli Thiaine , Kulikova Maria , Shathasivam Premalatha , Wilson Gavin , Darling Gail , Coburn Bryan , Yeung Jonathan 
Published: August 2023

Abstract

Background
Esophageal adenocarcinoma (EAC) is a highly heterogeneous cancer with a current five-year survival rate of ~18%. To improve outcomes, understanding factors impacting treatment response is imperative. Gut microbiome signatures are one such factor and have been associated with response to immunotherapy and survival in several solid cancers. Thus, we aim to identify variations in gut microbiome signatures at different stages of treatment and elucidate the link of these signatures to treatment responses and patient outcomes.

Methods
Fecal samples were collected from 50 patients prior to induction and 18 during or post induction and stored at −20 ̊C before extracting DNA using the QIAamp DNA Mini Kit. Extracted DNA was quantified and 16S gene expression was confirmed by qPCR using primers targeting the V3-V4 region of the 16S gene, following which 16S rRNA sequencing was performed.
FastQC, MultiQC and Cut Adapt were used for quality control of sequence data before assembly with vsearch. The resulting data was processed following the deblur pipeline. Taxonomy was assigned using Qiime2 classift-hybrid-vsearch-sklean function. Statistical comparison of diversity was conducted in R.

Results
Species diversity within individual samples, the alpha diversity, showed no significant difference between baseline and post-induction samples. Likewise, the comparison of diversity between samples, the beta diversity, showed no significant clustering on baseline compared to post-induction.
On the genus level, there was no significant statistical difference between the normalized counts of individual genera shared between baseline and post-induction samples.

Conclusion
These preliminary results suggest that induction therapy has minimal impact upon species richness of the gut microbiome when compared to baseline as measured by fecal microbiome. Future directions of this project include examining the gut microbiome at further stages of treatment and investigating the microbiome of the tumour itself.
364. A CASE OF SEVERE REFRACTORY MASSIVE MASTOID ASCITES AFTER THORACIC DUCT LIGATION FOR POSTOPERATIVE MASTOIDECTOMY
Authors: Ken Ito , Takashi Kamei , Motohisa Hagiwara , Masahiro Chin , Yasuyuki Hara , Eiji Hashizume 
Published: August 2023

Abstract
The patient, a male in his 70s, was referred to our hospital after an upper gastrointestinal endoscopy revealed esophageal cancer. After a close examination, he was diagnosed with esophageal squamous cell carcinoma T3, N2, M0, Stage III. After preoperative chemotherapy, he underwent thoracoscopic esophagectomy and gastric tube reconstruction. Intraoperatively, the thoracic duct was injured on the cranial side of the aortic arch and was ligated with a clip. When tube feeding was started postoperatively, a pleural effusion was observed, and the patient was treated with central venous nutrition. The effusion did not improve, so thoracoscopic surgery was performed on the postoperative day 12, and the thoracic duct was ligated just above the diaphragm. Postoperatively, the patient developed ascites in addition to pleural effusion, and continued to totally drain 3000 mL of thoracoabdominal fluid every day. Lymphangiography showed that lymphatic flow was interrupted at the site of thoracic duct ligation, but the site of leakage was unknown. Based on previous reports, octreotide 300 μg and etilefrine 100 mg was administered continuously, and pleural drainage decreased, and ascites drainage increased. Ascites volume exceeded 3000 mL in three days and was treated with a single puncture, but no improvement was observed. Tolvaptan 3.75 mg was started, and ascites decreased gradually. Patient’s general condition improved with nutrition and rehabilitation, and he was discharged on the day 189. We report a very rare case of refractory massive ascites following thoracic duct ligation for postoperative chylothorax, along with a discussion of the relevant literature.