bluuebunny/crossref_metadata_2025_split huggingface dataset:
416. BIOMARKER IDENTIFICATION FOR CHEMOTHERAPY RESPONSE PREDICTION IN BARRETT’S CARCINOMA PATIENTS BY AN INFLAMMATORY-RELATED PLASMA PROTEIN PROFILING
Authors: Thieme René , Mehdorn Matthias , Netto Jeffrey , Schierle Katrin , Lordick Florian , Thiery Joachim , Gockel Ines 
Published: September 2022

Abstract
The prognosis of patients with advanced esophageal adenocarcinoma (EAC) is still poor, which is partly due to a limited chemotherapy response. About 50% of these patients, treated with neoadjuvant chemotherapy, are non-responder, which might by influenced by inflammation and immunological conditions.
EAC patients (n = 24) were characterized prospectively in a single center study for gender (female n = 4; male n = 20), age (median 64; range 43-77 years), TNM-classification, and pathological response rate (PRR) to neoadjuvant chemotherapy. PRR was assessed according to the Schneider classification (Grade 3 + 4 total + subtotal remissions were defined as good responders). A comprehensive high performance inflammation biomarker panel, including 92 inflammatory-related proteins, was conducted in plasma (OLINK, Uppsala, Sweden). Blood was taken before neoadjuvant chemotherapy induction (baseline) and after chemotherapy completion. EAC cell lines (OE33, OE19, SK-GT-4, FLO-1) were treated with the chemokine (C-X3-C motif) ligand 1 (CX3CL1) for 48 h.
Nineteen inflammatory-related proteins were altered significantly after neoadjuvant chemotherapy completion. The five most affected proteins were TNF, IFNγ, CX3CL1, FLT3L, and PD-L1. Pathway analyses revealed an activated IL10- and IL18-signalling pathway, after neoadjuvant chemotherapy. A PRR of 3 and 4 correlated significantly with higher baseline CX3CL1 values. CX3CL1 treatment led to decreased proliferation rates in two (OE19 and SK-GT-4) of the four investigated EAC cell lines by 25-50%. Values for GDNF were higher, while values for TRAIL and TNFRSR9 were lower in patients’ plasma with a good PRR after chemotherapy completion as compared to patients with a poor PRR.
Multiplex profiling of inflammatory-related biomarkers revealed an activated interleukin signaling, (IL10- and IL18 pathway) after neoadjuvant chemotherapy. Inflammatory plasma proteins as CX3CL1 could be an interesting candidate to predict PRR and to identify patients, who will benefit from neoadjuvant chemotherapy. However further prospective studies are needed to validate our first observations.
421. THE STAPLED ANASTOMOSIS IN ESOPHAGECTOMY: NO DIFFERENCES IN LEAKAGE AND STRICTURE-RATES BETWEEN THE 25 MM AND 28 MM CIRCULAR STAPLER
Authors: Tagkalos Evangelos , Uzun Eren , Berlth Felix , Lang Hauke , Van der Sluis Pieter C , Grimminger Peter P 
Published: September 2022

Abstract
For patients undergoing an Ivor Lewis esophagectomy with a circular stapled anastomosis, the optimal diameter of the used circular stapler to restore continuity is unknown. The aim of this study was to compare the 25 mm stapled versus the 28 mm stapled esophagogastric anastomosis after Ivor Lewis esophagectomy, focusing on anastomotic insufficiency and post- operative anastomotic strictures.
Between February 2008 and June 2019, 349 consecutive patients underwent Ivor Lewis esophagectomy with gastric conduit reconstruction and circular stapled anastomosis. Patient characteristics and postoperative results, such as anastomotic insufficiency rates, postoperative anastomotic stricture rates, time to anastomotic stricture rate, and the number of dilatations, were recorded in a prospective database and analyzed.
In 222 patients (64%), the 25 mm circular stapler was used. There were no differences in baseline characteristics. Anastomotic insufficiency rates were comparable between the 25 mm (12%) and the 28 mm groups (11%) (p = 0.751). There were no differences between postoperative anastomotic strictures in the 25 mm (14%) and the 28 mm groups (14%) (p = 0.863). Within patients with postoperative anastomotic strictures, a median number of 2 dilatations were observed in each group (p = 0.573) without differences in the time to first diagnosis (p = 0.412).
There were no differences in anastomotic insufficiency and postoperative anastomotic stricture rates between the 25 mm and the 28 mm circular stapled esophagogastric anastomosis after Ivor Lewis esophagectomy. Both the 25 mm and 28 mm stapler can be safely used to create a circular stapled esophagogastric anastomosis to restore continuity after esophagectomy.
427. CHARACTERIZATION OF THE CYTOSKELETON-ASSOCIATED PROTEIN 4 (CKAP4) IN A BARRETT’S ESOPHAGUS CELL CULTURE MODEL
Authors: Limberger Beate , Ludwig Alexandra , Lyros Orestis , Nowotny Robert , Gockel Ines , Thieme René 
Published: September 2022

Abstract
While the incidence of EAC is rapidly increasing, its prognosis remains poor, with a five-year survival rate of 20%. Consequently, the discovery of new molecular targets for an efficient characterization of EAC patients is necessary. CKAP4 has been attributed to be increased in various cancer entities and has a role in tumorigenesis. However, its role in EAC development and progression is widely unknown.
In a Barrett’s esophagus, in vitro cell culture model of BE and EAC, CKAP4 expression levels were verified with qPCR, western blot and FACS analysis. In OE33 and OE19 cells a knockdown of CKAP4-expression was done by siRNA for 48 h and 72 h. In siCKAP4 transfected cells FACS (apoptosis), western blot analysis, colony forming assay (CFA), transmigration, adhesion and proliferation assays, were performed. Using western blot, the impact of CKAP4-knockdown on the phosphorylation of Akt, MAP-Kinase, GSK3ß and ß-Catenin was investigated. Furthermore, DKK1-, Ki67- and p21-mRNA-expression was analyzed in siCKAP4 cells using qPCR.
CKAP4 was present in all cell lines of the Barrett’s sequence (squamous epithelium, metaplasia, dysplasia, and EAC). CKAP4 surface expression was significantly increased in OE33, OE19 and Flo-1 cells. The phosphorylation of Akt was decreased in OE19 cells only, whereas the phosphorylation of MAP-kinase was reduced in OE33 cells, suggesting a role of CKAP4 in tumor-associated proliferation. This was confirmed by decreased colonies in CFA in siCKAP4 cells. FACS analysis showed a significant increase in the amount of apoptotic cells after siCKAP4 transfection. SiCKAP4 led to an increased expression of adhesion molecules, suggesting an impact of CKAP4 in cell adhesion.
The role of CKAP4 is barely investigated in EAC at this time. Acting as a Dickkopf-1 (DKK1) receptor, the DKK1-CKAP4-axis might promote cell proliferation independently to the Wnt-pathway. Based on our current results, it can be assumed, that CKAP4 is important for EAC cell growth, proliferation and cell adhesion. Nevertheless, further characterization of CKAP4 is necessary, particularly focusing on the CKAP4-DKK1-axis to provide more evidence for its contribution in EAC development.
431. THORACOSCOPIC ESOPHAGEAL CANCER SURGERY IN THE LEFT LATERAL POSITION WITH EMPHASIS ON SAFETY AND RADICAL CURE
Authors: Sato Hiroshi , Miyawaki Yutaka , Lee Seigi , Sugita Hirofumi , Sakuramoto Shinichi 
Published: September 2022

Abstract
Compared with thoracoscopic esophagectomy in the prone position (PP), the conventional thoracoscopic esophagectomy in the left lateral position (LL) with artificial pneumothorax is slightly more difficult for dissection of the middle and lower mediastinum, but is superior to PP because the operation can be performed with good visual field in the upper mediastinum. The purpose of this study was to clarify the safety and curative potential of this technique.
We retrospectively reviewed 246 cases of thoracic esophageal cancer surgery from April 2012 to December 2018. Thoracoscopic surgery (group V) was performed in 154 patients and open right thoracotomy (group O) in 92 patients. When this procedure was judged to be feasible, it was started thoracoscopically, and when it was judged to be unfeasible, a small thoracotomy of about 10–15 cm was added to allow one hand to enter. Thoracoscopy not only reduces the invasiveness of the procedure, but also allows us to share the anatomy, and improves the maneuverability of esophageal transfer and ensures safety in emergency situations.
Postoperative complications with Clavien-Dindo classification II or higher were 40% in group O and 51% in group V. In group V, anastomotic leak was 15 (9.7%), vocal cord paralysis 34 (22%), pneumonia 17 (11%), SSI 16 (10%). The mean postoperative hospital stay was 20 days. 8 (8.7%) patients in the O group had anastomotic leak, 10 (11%) had vocal cord paralysis, 8 (8.7%) had pneumonia, 12 (7.8%) had SSI. The mean postoperative hospital stay was 28 days. Of 27 salvage procedures, 14 (52%) were performed thoracoscopically. Thoracoscopic surgery was completed in 10 cases and combined thoracotomy in 4 cases.
Short-term outcomes of thoracoscopic surgery show an increase in vocal cord paralysis compared to open surgery. The procedure does not improve infectious complications. This technique has the advantage of easy conversion to open thoracotomy, including in emergency situations, and is more advantageous in advanced cancer, and can be a curative and safe treatment for highly advanced cancer.
451. CLINICAL PATTERNS AND TREATMENT OUTCOMES OF OESOPHAGEAL PERFORATION—A TEN-YEAR RETROSPECTIVE ANALYSIS FROM A TERTIARY CENTER IN SOUTH INDIA
Authors: Sigamony Negine Paul Paul , Yacob Myla , Surendran Suraj , Chandran Sudhakar , John Anoop , Simon Ebby , Samarasam Inian 
Published: September 2022

Abstract
Oesophageal perforation is a rare, often life-threatening clinical condition with reported mortality rates of 18 to 25%. Early diagnosis is often challenging with many patients presenting late and in shock. Management is even more challenging with a myriad of options but no standard options or criteria. We aim to review our ten-year experience of managing oesophageal perforation and propose an algorithmic approach for managing this condition.
A retrospective review of patients diagnosed with oesophageal perforation from 2011 to 2020 was done. Oesophago-gastric anastomotic perforations and corrosive injuries were excluded. The data relevant for the study including Pittsburgh Severity Score (PSS) was collected from the hospital electronic medical records and strengthened using telephonic conversation.
Thirty-six patients (M: F-26:10, mean age: 48 years) were included. In 21 (58%) patients, the perforation was localized to the thoracic oesophagus. The commonest cause of perforation was Iatrogenic (n = 22, 61%), followed by spontaneous (n = 9, 25%). A severe PSS score (≥7) was associated with increased risk of operative intervention (76%) and mortality (18%). Eighteen patients (50%) required operative interventions wherein a primary repair was performed in seven (39%) patients, sepsis drainage in eight (44%) patients, and a diversion in one (6%) patient. Overall, eleven (31%) patients required a re-intervention, and the overall in-hospital mortality was 8.3%.
Early diagnosis and decision making using an algorithmic approach are critical in the management of oesophageal perforation. PSS score is a useful tool in assessing the severity of disease. A combined multidisciplinary approach involving therapeutic endoscopy, surgery, and critical care is essential. A minimally invasive surgical approach is a feasible option in selected group of patients.
456. THE PROGNOSTIC IMPACT OF TUMOR BUDDING IN ESOPHAGEAL ADENOCARCINOMA
Authors: Fiocca Roberto , Mastracci Luca , Lugaresi Marialuisa , Grillo Federica , D'Errico Antonietta , Malvi Deborah , Spaggiari Paola , Tomezzoli Anna , Albarello Luca , Ristimäki Ari , Bottiglieri Luca , Bonora Elena , Krishnadath Kausilia K , Rosati Riccardo , Romario Uberto Fumagalli , De Manzoni Giovanni , Räsänen Jari , Mattioli Sandro 
Published: September 2022

Abstract
In a previous study on esophageal adenocarcinoma (EAC) cases submitted to surgery (without neoadjuvant treatment), an algorithm (EACGSE classification) 1 based on morphologic distinctions provided significant prognostic impact. Tumor budding is a specific type of invasive growth pattern and was found to be an important prognostic parameter in gastrointestinal cancers. 2–3 We aimed to evaluate the prevalence of budding in glandular adenocarcinomas and its impact on survival.
The EAC cohort classified according to EACGSE 1 was included in the study: among the different histotypes, 215 cases, classified as well (WD) and poorly (PD) differentiated glandular adenocarcinomas, were considered. Tumor budding was defined as single cells or clusters of up to four cells at the invasive margin. Budding was grouped according to ITBCC 2 into Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (10 or more buds). Furthermore, the most prognostically relevant cut off for bud number in EAC was defined by ROC analysis. Cancer specific survival analyses were performed using the Kaplan–Meier method and Cox regression analyses.
Tumor budding was assessed in one hotspot (a field measuring 0.785 mm2) at the invasive front and ROC analysis identified 8 buds per field cut off as the most informative in relation to survival. By using this cut off, frequency of budding was higher in glandular PD (84/124,68%) cases than in WD ones (7/91,8%, p &lt; 0.001). Budding was a strong negative predictor of survival both in univariate (p &lt; 0.001) and multivariate analyses (p &lt; 0.001) (Fig. 1). Using the 3 categories proposed by ITBCC, 2 budding was significantly related to survival in univariate analysis (p = 0.006) but lost significance in multivariate analysis.
Tumor budding showed a prognostically negative impact in glandular EACs. The 8 buds per field cut off appears to provide the best prognostic discriminant. Tumor budding assessment should be added to the identification of other prognostic factors already described in the same series (stage, histotype and vascular invasion). 1
457. STANDARDIZATION AND SHORT-TERM RESULTS OF ROBOT-ASSISTED THORACOSCOPIC ESOPHAGECTOMY
Authors: Koyanagi Kazuo , Kazuno Akihito , Yamamoto Miho , Higuchi Tadashi , Yatabe Kentaro , Kanamori Kohei , Tajima Kohei , Nakamura Kenji , Nabeshima Kazuhito , Ogimi Mika 
Published: September 2022

Abstract
Surgical cases of robot-assisted thoracoscopic esophagectomy (RAMIE) is increasing because of the advantages of robotic system. We introduced RAMIE in 2019 and standardized the surgical procedure. The usefulness of RAMIE was examined by classifying surgical cases into early and late periods and comparing the surgical results.
Fifty-four patients who underwent RAMIE were enrolled in the study. All patients underwent D2 or higher lymph node (LN) dissection, gastric tube reconstruction, and R0 surgery. The patients were divided into two groups, 26 cases in the first half up to December 2020 and 28 cases in the second half after January 2021. The patient background, surgical technique, and short-term results were compared. The tumor staging was based on the UICC 8th version.
Thoracic surgery time was 274 minutes, the chest bleeding volume was 30 mL, and the postoperative hospital stay was 19 days (median). In the late stage, patients with clinical thoracic LN metastasis (p = 0.01) and advanced stage (p = 0.006) were higher than those in the early period. There were significantly more cases of thoracic duct resection and D3 dissection in the late period (p = 0.02, p = 0.009). No differences in postoperative complications and intra-hospital death was observed, however the postoperative hospital stay was significantly shortened in the late period (p = 0.001).
Thorough mediastinal LN dissection by RAMIE could be safely performed by standardizing and improving the surgical procedures. RAMIE has several issues such as higher cost associated with equipment and longer operative time, but it is possible to perform precise procedures with solo surgery, and it is expected that cost reduction effects will be expected in terms of the number of participants in surgery and the length of hospital stay after surgery.
466. OUTCOME OF NIVOLUMAB FOR UNRESECTABLE ADVANCED OR RECURRENT ESOPHAGEAL CANCER IN OUR INSTITUTION
Authors: Tabuchi Satoshi , Takano Yuki , Ochiai Shigeto , Gunji Takahiro , Kobayashi Toshimichi , Suzumura Hirofumi , Shigoka Masatoshi , Chiba Naokazu , Hidaka Eiji , Kawachi Shigeyuki 
Published: September 2022

Abstract
In recent years, drug therapy for esophageal cancer has seen rapid progress, including immune checkpoint inhibitors. Guidelines for the treatment of esophageal cancer recommend nivolumab as second-line therapy. We report the results of nivolumab for unresectable advanced or recurrent esophageal cancer in our institution, including the cases that responded to the therapy.
We analyzed 12 patients (male: female = 10:2, median age: 67 years) treated with nivolumab for unresectable advanced or recurrent esophageal cancer between March 2020 and March 2022.
The status of treatment, response rate, adverse effects, and conversion rate to next line were analyzed for these patients.
The median follow-up period was 4.2 months, and the median number of treatment cycles was 5 (2-41). Response rate was 17%, and disease control rate was 42%. Adverse effects included one case (8%) of severe diarrhea, considered ir-AE. The patient was treated with steroids. The rate of conversion to next-line treatment was 17% (2 cases).
Nivolumab for esophageal cancer has a good prognosis in patients who respond to it. In addition, it is important to pay attention to ir-AE, perform imaging and physical examinations, and evaluate accurately and treat quickly.
476. SONIC HEDGEHOG POSITIVE EXPRESSION IS ASSOCIATED WITH PROGNOSIS AND THE RESPONSE OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA TO NEOADJUVANT CHEMOTHERAPY
Authors: Sun Haibo , Liu Xianben , Xing Wenqun , Feng Shaokang , Jiang Duo , Yan Sen , Ma Yaxing 
Published: September 2022

Abstract
Neoadjuvant therapy follow by surgery is the standard treatment mode for patients with locally advanced esophageal squamous cell carcinoma (ESCC). This research aimed to investigated the potential of sonic hedgehog (Shh), glioma-associated oncogene homolog1 (Gli1) and Phospho-S6 (p-S6) to predict the response of ESCC to neoadjuvant chemotherapy.
Firstly, the expressions of Shh, Gli1 and p-S6 in cancer tissues and normal tissues of 49 ESCC patients without neoadjuvant therapy were detected by immunohistochemistry. A total of 390 ESCC patients were included in the nest study, and 44 pairs of patients with or without neoadjuvant chemotherapy were matched after 1:1 propensity score matching to evaluate the effect of neoadjuvant chemotherapy on the expression of Shh, Gli1 and p-S6. The relationship between Shh, Gli1, and p-S6 expression and the outcomes of neoadjuvant chemotherapy was analyzed retrospectively.
The expressions of Shh (positive/negative: 25/24 vs. 0/49, P﹤0.001), Gli1 (24/25 vs. 0/49, P﹤0.001) and p-S6 (16/33 vs. 0/49, P﹤0.001) in cancer tissues were significantly higher than those in normal tissues. Neoadjuvant chemotherapy did not change the expression of Shh (24/20 vs. 23/21, P=0.109), Gli1 (23/21 vs. 21/23, P=0.839) and p-S6 (10/34 vs. 15/29, P=0.383) in ESCC cancer tissues. Among them, the positive expression of Shh was associated with poor tumor regression grade (TRG2-3/TRG1: 23/1 vs. 12/8, P=0.003) and poor 5-year survival rate (44.7% vs. 65.8%, P=0.041).
The expressions of Shh, Gli1 and p-S6 were increased significantly in ESCC and were not affected by neoadjuvant chemotherapy. Shh is a significant predictive indicator of ESCC response to neoadjuvant chemotherapy and prognosis.
477. TEXTBOOK OUTCOMES FOR OESOPHAGECTOMY: AN EVALUATION OF OESOPHAGECTOMY QUALITY PERFORMANCE INDICATORS AT A SINGLE HIGH-VOLUME AUSTRALIAN OESOPHAGOGASTRIC CENTRE
Authors: Wu M , McGregor R , Scott J , Smithers M , Frankel A , Barbour A , Thomson I 
Published: September 2022

Abstract
In 2017 the Dutch Upper-Gastrointestinal Audit Group (DUCA) proposed a ten-item composite measure for a “textbook outcome” after oesophagogastric resection. Utilising this composite measure, studies have shown associations between textbook outcomes and better conditional and overall survival. The aim of our study was to evaluate the applicability of this measure in the setting of an Australian oesophagogastric centre and to ascertain whether textbook outcome was associated with improved survival.
Data were obtained by retrospective analysis of a prospectively maintained database of oesophagogastric malignancies at a single oesophagogastric unit from 2013 to 2018. We used the DUCA group definition of textbook outcomes, encompassing resection radicality, resection margins, lymph node clearance, intra- and post-operative complications, length of stay, hospital and intensive care unit re-admissions, and post-operative mortality. Multivariable logistic regression analysis was conducted to assess association between patient factors and textbook outcome. Cox regression analysis was used to assess association between textbook outcome and survival. Post-operative complications were analysed in two separate groups (Clavien-Dindo ≥2 and Clavien-Dindo ≥3).
A total of 246 patients were analysed, with 50.8% achieving a textbook outcome when complications were defined as Clavien-Dindo ≥2 and 58.9% when using Clavien-Dindo ≥3. Patients with age &lt;75 or a respiratory co-morbidity were less likely to achieve a textbook outcome. The 30-, 90-day and 1-year mortality rates were 1.6%, 2.4% and 15% respectively. There was no difference in survival between those who did versus those who did not have a textbook outcome when complications were defined as Clavien-Dindo ≥2. There was improved overall survival if complications were defined as Clavien-Dindo ≥3 (HR0.58, p=0.015).
Textbook outcome is a new multi-parameter metric that aims to better capture the quality of oesophageal cancer surgery compared to traditional volume-outcome relationships. We have demonstrated that it is applicable in our population, with the percentage of patients having a textbook outcome comparing favourably with published data. In our series, a textbook outcome was associated with improved overall survival when defining complications as Clavien-Dindo ≥3.