bluuebunny/crossref_metadata_2025_split huggingface dataset:
380. INTEGRATIVE TRANSCRIPTOMIC AND FUNCTIONAL ANALYSIS OF CHEMOTHERAPY RESISTANCE IN ESOPHAGEAL ADENOCARCINOMA
Authors: Kong Mingyang (Iris) , Pal Sanjima , Qian Qiu , Tai Kulsum , Osman Nathan , Berube Julie , Bourdeau France , Zeng Wotan , Giannias Betty , Huang Sui , Bailey Swneke , Sangwan Veena , Bertos Nick , Ferri Lorenzo 
Published: August 2023

Abstract

Background
Gastroesophageal Adenocarcinoma (GEA) is one of the most lethal malignancies in North America with a 5-year survival of &lt;20%. Currently, the standard-of-care treatment for GEA patients is docetaxel-based triplet chemotherapy. However, around 40% of patients are innately resistant to chemotherapy, and half of the initial responders develop acquired resistance during treatment. There is an urgent need to understand the molecular mechanisms driving chemotherapy resistance and identify alternative therapeutic options.

Methods
Primary tumor tissue was collected from 29 GEA patients to generate patient-derived organoids (PDOs). PDOs were treated with chemotherapy, and the cell viability was measured using Cell Titer Glo. A 3200-compound library was screened at a single concentration (1uM) on three chemo-resistant PDOs. Compounds that showed efficacy in all three lines were then tested in combination with chemotherapy to evaluate their synergistic effects. Single-cell RNA sequencing (scRNA) was performed for 8 chemo-sensitive and 16 chemo-resistant patients. We conducted a transcriptomic analysis to identify markers that are differentially expressed in the two groups. Pathway analysis was performed using Gene Set Enrichment Analysis.

Results
Cell viability of the PDOs obtained from chemo-resistant patients was significantly higher than that of chemo-sensitive patients. High-throughput (HTP) screening revealed 21 drugs that showed efficacy in all three PDOs, including inhibitors for ribosomes, oxidative phosphorylation (OXPHOS) pathway, and NFkB pathway. Correspondingly, scRNA analysis indicated that chemo-resistant patients have up-regulated ribosome biosynthesis and OXPHOS pathways, as well as increased expression of CCND1, which is a downstream target of the NFkB pathway. Furthermore, the IGF1R inhibitor Ceritinib demonstrated a significant synergistic effect when combined with chemotherapy, with a synergy score of 19.9.

Conclusions
GEA organoids recapitulate the chemotherapy response of patients, making them an ideal model for ex-vivo drug testing. Integrative analysis of the HTP functional screening and scRNA sequencing data revealed ribosome biogenesis, OXPHOS pathway and IGF-1R as potential therapeutic targets to overcome chemoresistance in GEA.
385. HOSPITAL COSTS OF POSTOPERATIVE ADVERSE EVENTS FOLLOWING ESOPHAGECTOMY: RESULTS FROM 10 CANADIAN INSTITUTIONS
Authors: Jones Daniel , Anstee Caitlin , Gingrich Molly , Yasufuku Kazuhiro , Malthaner Richard , Safieddine Najib , Finley Christian , Kidane Biniam , French Danny , Ferri Lorenzo , Graham Andrew , Seely Andrew 
Published: August 2023

Abstract

Background
Surgical resection plays a central role in the multimodal curative intent management of esophageal cancer. Despite advances in peri-operative care, 60% of patients undergoing esophagectomy experience postoperative adverse events (AEs), if AEs are prospectively collected by surgeons. We recently performed a systematic review documenting the published index hospital costs of AEs, yet the overall costs of AEs in Canadian esophageal centres remains unknown.

Methods
Between 2017–2021, prospectively collected data from 10 Canadian esophageal centres were included. Volumes of esophagectomy, incidence of postoperative AEs (anastomotic leak (AL), pneumonia, respiratory failure), graded using the Ottawa TM&M system [ottawatmm.org], and obtained from 2 Canadian Association of Thoracic Surgeons (CATS) National Positive Deviance Seminars were included. Using literature-derived index hospitalization costs of AEs, estimates of annual costs were obtained (2023 Cdn$).

Results
Data from 795 esophagectomies performed in Canada between 2017–2019 revealed an average AL rate of 15% (8.7–22%). This led to an estimated yearly hospital cost of $6.63 M. Additional data from 863 esophagectomies performed between 2018–2021 revealed an average yearly pneumonia rate of 10.2% (2.4–20.3%)., with an estimated cost of $1.44 M, and respiratory failure (requiring ICU admission) of 7.8% (0–13.8%), with an estimated cost of $1.83 M. When all 10 centres are combined, these 3 AEs equate to over $9.9 M in hospital expenditures/year. A 1% reduction/year in the 3 AEs would lead to a cost-savings of $816,738.

Conclusion
Our analysis of only 3 post-operative AEs highlights the staggering costs to hospitals across Canada individually, and collectively, and emphasizes the need to support value-based QI research. Direct financial support from hospitals to support value-based QI in esophageal surgery has the potential to simultaneously improve care and provide valuable cost savings.
428. PHARYNGEAL SQUAMOUS CELL CARCINOMA AND RISK OF LATER ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Elbe Peter , Ekheden Isabella , Vujasinovic Miroslav , Maret-Ouda John , Marsk Elin , Thuresson Marcus , Roelstraete Björn , Ye Weimin , Ludvigsson Jonas F 
Published: August 2023

Abstract

Introduction
Pharyngeal squamous cell carcinoma is a known risk factor for later squamous cell carcinoma of the esophagus. We investigated whether the risk of esophageal carcinoma is high enough to justify routine gastroscopy surveillance in a northern European population. If the risk among patients with pharyngeal carcinoma corresponds to the risk among patients with Barretts esophagus of developing adenocarcinoma, it could justify surveillance.

Method
Histopathology data from pharyngeal and esophageal biopsies obtained 1980–2016 in Sweden’s 28 pathology departments were linked to national population-based healthcare registers. We calculated a subdistribution hazard ratio (HR) comparing the risk of esophageal cancer and death in patients with pharyngeal carcinoma to a matched general population.

Result
In total 1399 patients with pharyngeal cancer were identified. 344 were excluded due to age under 18 years, previous esophageal cancer, death or cancer within 6 months of diagnosis. Thus, 1055 patients remained. Median follow up time was 5,1 years. 78% were men and median age at diagnosis of pharyngeal cancer was 64 years. Four (0.38%) patients developed esophageal squamous cell carcinoma during follow-up, equal to 1 in 263 patients (HR = 14,32; 95%CI = 1,55-132,30). 855 of the patients (81%) died during follow-up (HR = 7,65; 95% = 6,82-8,59).

Discussion
The yearly risk of developing esophageal squamous cell carcinoma was 0,07%, which is lower than the risk among patients with Barretts esophagus. Therefore, we find no support for long-term endoscopic surveillance among patients with pharyngeal cancer.
475. CROSS X FLOT: WHICH ONE HAS LESS COMPLICATIONS?
Authors: Bianchi Edno Tales , Galleti Ricardo , Lucas Phellipe Fabbrini Santos , Reginaldo Tales Barione , Tustumi Francisco , Souza Jorge , Namur Guilherme , Azevedo Beatriz , Kruger Jaime 
Published: August 2023

Abstract

Background
Today there are 2 main neoadjuvant schemes for the treatment of esophageal tumors: CROSS and FLOT. There are still no data in the literature to categorically state which one is associated with greater complications and mortality and whether there is an impact on the quality of the lymphadenectomy.
We demonstrate our comparative data from each group undergoing curative treatment of esophageal tumor, along with associated complications and number of dissected lymph nodes at a single institution during the Covid-19 pandemic.

Methods
A retrospective analysis of 56 patients who underwent curative treatment of esophageal tumor by minimally invasive esophagectomy was carried out. The squamous cell carcinoma group (SCCG) were composed by 28 subjects and of these 23 underwent CROSS, denominated CROSS group (CG). 27 were in the adenocarcinoma of the esophagogastric junction group (AdG) and of these, 23 underwent FLOT, denominated FLOT group (FG).
Complications, in-hospital and 90-day mortality were analyzed, as well as the quality of lymphadenectomy and response to neoadjuvant treatment and compared between groups.

Results
Toxicity complication during preoperative treatment was 3 (10%) in the CG and 8 (28%) in the FG (p &lt; 0.05).
Post-operatory complications was seen 11 in the SCCG (3 pulmonary, 5 fistulas—1 death) and 10 in the AdG (2 pulmonary, 4 fistulas—2 deaths). When analyzing the groups submitted to neoadjuvant therapy (23 FLOT x 23 CROSS), the same number of 8 (34%) were identified with no difference in Clavien-Dindo scale severity.(p &gt; 0,05).
The mean of lymphonodes dissected were similar between 2 groups (27,01 ± 8). Complete response was 13% in FG and 21% in CG with 3 patients (13%) with ypt0n +.

Conclusion
The group submitted to CROSS had a greater tolerance during the preoperative treatment. There was no difference in the number of complications related to the neoadjuvant scheme, as well as the quality of the lymphadenectomy, suggesting that the treatment can be individualized for each patient.
480. ANTIREFLUX SURGERY’S LIFESPAN: 20 YEARS AFTER LAPAROSCOPIC FUNDOPLICATION
Authors: Vittori Arianna , Salvador Renato , Capovilla Giovanni , Riccio Federica , Nezi Giulia , Forattini Francesca , Provenzano Luca , Nicolett Loredana , Moletta Lucia , Costantini Andrea , Valmasoni Michele , Costantini Mario 
Published: August 2023

Abstract

Background
Laparoscopic Fundoplication (LF) is the surgical technique of choice for treating GERD, but only few studies report a follow-up beyond 15 years. The aim was to evaluate the results at least 20 years after laparoscopic fundoplication at a single national referral center for esophageal diseases.

Methods
We prospectively collected data on a cohort of consecutive patients who underwent LF between 1992–2001. Patients were divided into two groups: a GERD group (patients with pathological esophageal acid exposure and hiatal hernias &lt;3 cm) and a large hiatal hernia (HH) group (patients having type I &gt; 3 cm and types II-IV hiatal hernias). Patients were followed up for at least 20 years using endoscopy, barium-swallow, esophageal manometry, and pH monitoring. LF was defined failed in case of: GERD symptom recurrence (SS &gt; 10); recurrence of esophagitis; HH recurrence or slipped-fundoplication; pathological pH-monitoring; BE progression or adenocarcinoma onset.

Results
The study population consisted of 142 patients: 112 in the GERD group and 30 in the HH group. The characteristics of patients are shown on Figure 1. Conversion to open surgery proved necessary in 8 patients (5.6%). At a median follow-up of 22 years, 80.4% of the GERD patients and 63.3% of the HH patients were failure-free. Revisional surgery was necessary in 14 (9.8%) patients (9 GERD and 5 HH patients); indications were dysphagia (5 cases), slipped fundoplication or hernia recurrence (6 cases), abnormal pH-monitoring or esophagitis resistant to medical therapy (2 cases), and telescoping (one case). Two decades after LARS, 87.6% of GERD patients and 76.7% of HH patients were satisfied with the procedure.

Conclusions
The present study concerns one of the largest populations of patients who had undergone LF to have been followed up for more than 20 years at a single center. The findings showed that laparoscopic antireflux surgery is effective and durable (for &gt;20 years) in patients with uncomplicated GERD and, to a lesser extent, in those with a large hiatal hernia. The satisfaction rate more than 20 years after surgery almost reached 90% in the GERD group.
482. SECOND-LINE OF CAMRELIZUMAB PLUS NIMOTUZUMAB IN ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC): A SINGLE-ARM, OPEN-LABEL, PHASE 2 TRIAL
Authors: Xia Jin , Meng Xiangrui , Ji Yinghua , Yang Xiuli , Hong Yonggui , Wang Junsheng , Cui Donghai , Wang Feng 
Published: August 2023

Abstract

Background
Anti-PD-1 antibody camrelizumab monotherapy is recommended for the treatment of advanced second-line ESCC. However, the long-term survival is limited, and new effective treatments are needed. Epidermal growth factor receptor (EGFR) is usually over-expressed in more than 50% of ESCC patients(pts), and is a potential target for the treatment of ESCC. Our study aimed to assess the efficacy and safety of combination with camrelizumab and nimotuzumab (EGFR inhibitor) as second-line treatment for advanced ESCC.

Methods
This ongoing phase II trial in four sites in China enrolled pts aged 18–75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line treatment, and ECOG PS score of 0–1. Pts received 200 mg intravenous camrelizumab (Q2W) plus 400 mg intravenous nimotuzumab (QW) in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed objective response rate (ORR), overall survival (OS). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS).

Results
From 2/2021 to 4/2023, 28 of the planned 42 pts with an average 63 years old had been enrolled, including 18 (64%) males and 21 (75%) patients with an ECOG PS score of 1. Nine pts had previously used anti-PD-1/PD-L1 antibody. Among the 21 evaluable pts, 8 pts achieved partial response (PR), 13 pts stable disease (SD), illustrating an ORR of 38.0% and a DCR of 100%. Median PFS was not reached. 82.1% pts experienced adverse event(AE), with 21.4% being grade ≥ 3. The most frequent AE were RCCEP (57.1%), neutrophil count decreased (17.8%), white blood cell decreased (14.2%).

Conclusions
Camrelizumab plus nimotuzumab demonstrated encouraging clinical efficacy and acceptable safety as second-line treatment, and might be a favorable option for pts with advanced ESCC. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03766178.
485. MATTHEW EFFECT OF NEOADJUVANT THERAPY IN ESOPHAGEAL CANCER
Authors: Liu Yixin , Yang Yushang , Chen Longqi 
Published: August 2023

Abstract

Carcinoma.

Background
Neoadjuvant therapy benefits long-term survival to patients with locally advanced Esophageal Squamous Cell Carcinoma (ESCC). If the survival benefit brought by neoadjuvant therapy is considered as a positive improvement for majority patients, outweighing the negative harms, it means that some patients will experience a reduction in survival due to the negative harms, just as the Matthew effect. This study focuses on these failures of Matthew effect who may not benefit from neoadjuvant therapy and explores the specific recurrent patterns.

Method
A total of 457 recurrent ESCC patients undergoing curative esophagectomy were enrolled, including 140 patients treated with neoadjuvant therapy. The median progression time (MPT) were 24.3 months. Tumor recurrences or metastases occurring before MPT were defined as treatment failure. We retrospectively investigated the patterns of recurrence and the prognosis in patients with neoadjuvant therapy.

Results
Among recurrent patients, locoregional recurrence, lung and bone metastases were the most common recurrence sites. The median progression time to the first recurrence was 24.3 months. The locoregional recurrence rate of neoadjuvant group was lower than that of none-adjuvant group (46% vs 60.2%), while the liver and brain metastasis rates was higher (16% vs 7.5% and 8.1% vs 3.3% respectively). Kaplan–Meier analysis showed unsatisfactory prognosis for neoadjuvant therapy failures than those without neoadjuvant therapy. Moreover, for non-neoadjuvant ESCC, shorter overall survival was found in distant recurrence failures than those with locoregional recurrence, while the different recurrence patterns shared similar prognosis for neoadjuvant therapy failures.

Conclusion
For treatment failure patients with early progression, neoadjuvant therapy has an advantage in controlling local recurrence, but this positive improvement does not transform into survival benefits, indicating Matthew effect of neoadjuvant therapy in ESCC.
491. VITAMIN B12 DEFICIENCY AFTER ONCOLOGICAL ESOPHAGECTOMY AND GASTRECTOMY
Authors: Sallakhi Aria , Baumgartl Isabella Alexandra , Andresen Julian Ramin , Khater Hagar , Gibas Georg , Medibach Amadea , Marolt Cordula , Radlspöck Wolfgang , Zacherl Johannes 
Published: August 2023

Abstract
Vitamin B12 deficiency is common in patients with resections of the upper digestive tract and must be expected during follow-up examinations. While esophagectomy with gastric pull-ups preserve the duodenal passage and a large part of the stomach, (sub)total gastrectomies result in significant losses of gastric tissue and the common Y-Roux reconstruction bypasses the duodenal passage.
This is a monocentric, retrospective, descriptive analysis of prospectively collected follow-up data. Between January 2015 and December 2019, 232 patients underwent an oncological (sub)total gastrectomy or esophagectomy.
After applying the exclusion criteria (patient below 18, primary bone marrow disease, hereditary forms of anemia, postoperative tumor recurrence, R1/R2 situation), 157 patients remained for analysis: 103 patients (=66%) with esophagectomy (ER) and 54 (=34%) with (sub)total gastrectomy (SGE). Vitamin B12 levels were analyzed three, six, twelve, 18, and 24 months after the surgery. Prophylactic intramuscular vitamin B12 substitution (Erycytol 1 mg depot) was routinely prescribed quarterly only in patients with a total gastrectomy.
After 3 postoperative months the incidence of vitamin B12 deficiency were 24% in the ER group vs. 5% (p = 0,064) in the SGE group; 17% vs. 10% (p = 0.4) after 6 months; 8% vs. 5% (p = 0.65) after 1 year; 10% vs. 10% (p = 0.83) after 18 months, and 12.5% vs. 39% (p = 0.022) after 2 years. The resulted incidence of hyperchromic macrocytic anemia is furtherly discussed in the abstract entitled ‘Types and incidence of postoperative anemia after oncological esophageal and gastric resections’. Comparing the total gastrectomy versus subtotal gastrectomy subgroups, patients with a subtotal gastrectomy have higher vitamin B12 deficiency incidences throughout the 24-month follow-up period.
The human body physiologically provide a sufficient vitamin B12 storage for minimum 6–9 months. The high incidence of vitamin B12 deficiency in the ER group in the first 6 postoperative months might be due to a pre-existing vitamin B12 deficiency.
After the 6th postoperative month there is an approximation between the Vitamin B12 deficiency incidences of ER and (S)GE patients. In the final 2-year follow-up, the incidence of vitamin B12 deficiency was significantly higher in the (S)GE group.
492. TYPES AND INCIDENCE OF POSTOPERATIVE ANEMIA AFTER ONCOLOGICAL ESOPHAGECTOMY AND GASTRECTOMY
Authors: Sallakhi Aria , Baumgartl Isabella Alexandra , Andresen Julian Ramin , Khater Hagar , Gibas Georg , Medibach Amadea , Marolt Cordula , Radlspöck Wolfgang , Zacherl Johannes 
Published: August 2023

Abstract
According to current literature, anemias that develop after oncological esophageal and gastric resections are classified as deficiency anemias. Due to the surgery-related changes in the mechanical and biochemical conditions of the upper gastrointestinal tract, there is an alteration in the processing and absorption of hematopoietic-relevant vitamins and trace elements like iron, vitamin B6, vitamin B12, folic acid, copper and essential amino acids in the postoperative phase.
Between January 2015 and December 2019, 232 patients underwent a (sub)total gastrectomy or esophagectomy at our center. In this monocentric retrospective analysis of prospectively collected follow-up data, 157 patients were included after applying the exclusion criteria: Age below 18, primary bone marrow disease, hereditary forms of anemia, postoperative tumor recurrence and R1/R2 situation. 103 patients (=66%) belonged to the esophagectomy group and 54 patients (=34%) to the (sub)total gastrectomy group. Preoperatively and three, six, twelve, 18, and 24 months postoperatively the following laboratory parameters were collected and descriptively analyzed: Hemoglobin, MCV, MCH, serum iron, ferritin, transferrin, and vitamin B12.
Two years after the oncological resection 28% of patients with esophagectomy, EE, and 48% of patients with (sub)total gastric resection, (S)GE, show anemia. Normocytic anemia was the dominant type. The MCV distribution of anemic patients in the EE group was as follows: 3% microcytic, 77% normocytic, and 20% macrocytic. The anemic patients in the (S)GE group show the following MCV distribution: 16% microcytic, 81% normocytic, and 3% macrocytic. The (S)GE collective has more anemic patients in percentage terms than the EE collective throughout the whole follow-up period. This difference is significant at the 12th (p = 0.032) and 18th-month (p = 0.023) postoperative follow-up.
A high percentage of patients with oncological resection of the upper gastrointestinal tract have a relevant postoperative anemia. The known postoperative iron and vitamin deficiencies, that would be associated with microcytic hypochromic and macrocytic hyperchromic anemia, are not the relevant causes for this anemia as it is predominantly a normocytic form. Normocytic anemia is an indication for an anemia of chronic disease. The reason for the predominance of normocytic anemia is not specifically known.
Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension
Authors: Danese Silvio , Panaccione Remo , Abreu Maria T , Rubin David T , Ghosh Subrata , Dignass Axel , Afzali Anita , Wolf Douglas C , Chiorean Michael V , Vermeire Severine , Jain Anjali , Charles Lorna , Lawlor Garrett , Osterman Mark T , Wu Hsiuanlin , Canavan James B , Petersen AnnKatrin , Colombel Jean-Frederic , Regueiro Miguel 
Published: August 2023

Abstract

Backgrounds and Aims
This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis.

Methods
Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates.

Results
This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently.

Conclusions
Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.