bluuebunny/crossref_metadata_2025_split huggingface dataset:
251. COMPARISON OF LAPAROSCOPIC SURGERIES WITH OR WITHOUT HAND-ASSISTED PROCEDURE IN THE ABDOMINAL PHASE OF THORACOSCOPIC ESOPHAGECTOMY IN THE PRONE POSITION
Authors: Goto Hironobu , Oshikiri Taro , Kato Takashi , Sawada Ryuichiro , Harada Hitoshi , Urakawa Naoki , Hasegawa Hiroshi , Kanaji Shingo , Yamashita Kimihiro , Matsuda Takeru , Kakeji Yoshihiro 
Published: September 2022

Abstract
Laparoscopic surgery is less invasive than open surgery in the abdominal phase of thoracoscopic esophagectomy in the prone position (TEP). Laparoscopic surgery (LAP) and hand-assisted laparoscopic surgery (HALS) for mobilization of the stomach and abdominal lymph node dissection have been standard procedures. We aimed to compare the safety and feasibility of those procedures in patients undergone TEP.
We evaluated 69 patients who underwent TEP and received gastric conduit reconstruction for esophageal cancer. The LAP group consisted of 42 patients, whereas the HALS group consisted of 27 patients. Surgical outcomes and postoperative complications (Clavien-Dindo classification, grade II or higher) were evaluated between the two groups.
No significant differences were found in age, sex, clinical T stage, clinical N status, and neoadjuvant chemotherapy status between the two groups. According to surgical outcomes, there were no significant differences in overall operation time and reconstruction route. Abdominal operation time was significantly shorter in HALS group than in LAP group (LAP: 157 min (73–238), HALS: 96 min (35–157), P &lt; 0.0001). No significant differences were observed in anastomotic leakage, recurrent laryngeal nerve palsy, pneumonia, and postoperative stay (LAP vs HALS: 19.0% vs 25.9%, P = 0.558; 2.4% vs 3.7%, P = 1.000; 16.7% vs 29.6%, P = 0.240; 31 days (16–83) vs 36 days (16–97), P = 0.301).
There were no significant differences in postoperative complications between the two groups. HALS is a feasible procedure with short abdominal operative time for patients with esophageal cancer.
253. RABEPRAZOLE IS EFFECTIVE FOR BILE REFLUX ESOPHAGITIS AFTER TOTAL GASTRECTOMY IN A RAT MODEL
Authors: Hashimoto Naoki 
Published: September 2022

Abstract
To evaluate the effect of PPI (Rabeprazole) on esophageal bile reflux in esophagitis after total gastrectomy.
Twenty -one 8 week old male Wistar rats were studied. They were performed esophagoduodenostomy of total gastrectomy to induce esophageal reflux of biliary and pancreatic juice. Five rats were performed the sham operation (Sham) (n = 8). On the postoperative day 7, they were treated with saline (Control) (n = 8) or PPI (Rabeprazole 30 mg/kg per day, ip) (n = 8) for 2 weeks. On the postoperative 21 days, all rats were sacrificed and each esophagus was evaluated histologically. Esophageal injury was evaluated by macroscopic and microscopic findings as well as the expression of COX2. We measured bile acid in the esophageal lumen and common bile duct.
The macroscopic ulcer score and microscopic ulcer length of the control group were significantly higher compared to those of the rabeprazole treated group. The expression of COX2 was significantly increased according to the immunostaing in the control group compared to rabeprazole treated group. Although there was no difference between the control and PPI groups in the total bile acids in the common bile duct, the bile acid in the esophageal lumen was significantly decreased in the rabeprazole treated group due to augmentation of the duodenal motor complex.
With this model, rabeprazole is good effect for reflux esophagitis after total gastrectomy from bile reflux. Bile acid is an important factor in the mucosal lesion induced by duodenal reflux.
PPI does not inhibit the secretion of bile acid from the common bile duct.
Therefore, we speculate PPI accelerates duodenal phase III migrating motor complex, accelerating duodenal passage of duodenal contents (bile acids), which should reduce duodenoesophageal reflux.
255. CURRENT STATUS IN POSTOPERATIVE SHORT-TERM OUTCOMES OF ESOPHAGEAL RECONSTRUCTION USING THE GASTRIC TUBE AND FREE JEJUNUM FOR CERVICAL ESOPHAGEAL CANCER
Authors: Miyawaki Yutaka , Tachimori Hisateru , Nakajima Yasuaki , Sato Hiroshi , Miyata Hiroaki , Sakuramoto Shinichi , Shimada Hideaki , Watanabe Masayuki , Kakeji Yoshihiro , Doki Yuichiro , Kitagawa Yuko 
Published: September 2022

Abstract
Cervical esophageal cancer is rare of esophageal cancers. Therefore, there is currently no survey for a large cohort of postoperative short-term outcomes. The gastric tube or the free jejunum are the two major reconstructed organs in esophageal reconstruction after esophagectomy for cervical esophageal cancer. This study aimed to clarify the current status of esophageal reconstruction by reconstructed organ after esophagectomy for cervical esophageal cancer, especially postoperative morbidities and mortality.
Based on the Japan National Clinical Database, 807 surgically treated cases of cervical esophageal cancer between January 1, 2016, and December 31, 2019, were enrolled. Clinical outcomes were compared between the gastric tube group and the free jejunum group.
The frequency of surgical site infection in organ space, anastomotic leakage, pneumonia, empyema, and chylothorax was significantly higher in the gastric tube group (10.0%, 17.9%, 16.7%, 2.0%, and 3.3%, respectively) than in the free jejunum group (2.9%, 6.7%, 11.1%, 0.0%, and 0.3%, respectively) (p = &lt;0.001, &lt;0.001, 0.029, 0.008 and 0.005, respectively). Significantly more patients in the gastric tube group required long-term hospitalization over 90 days (p = 0.039).
Although these two major reconstructed organs are often not oncologically selectable, our results suggested that the free jejunum reconstruction after esophagectomy for cervical esophageal cancer may be more desirable when confined resection of the cervical esophagus was oncologically acceptable.
263. EFFECTS OF PREHABILITATION AND POST-OPERATIVE HIGH-FLOW NASAL CANNULA AFTER OPEN ESOPHAGECTOMY ON PULMONARY COMPLICATIONS: A FEASIBILITY STUDY
Authors: Vecchiato Massimo , Deana Cristian , Ziccarelli Antonio , Raimondi Paola , Martino Antonio , Pontoni Marta , Patruno Vincenzo , Bassi Flavio , Petri Roberto 
Published: September 2022

Abstract
Pulmonary complications (PPC) are still reported in 30% of patients also after minimally-invasive esophagectomy in high volume centers. 1–2.
Prehabilitation programs are promising in ERAS protocols. 3 Open esophagectomy (OE) has the lowest anastomotic leakage rate but higher PPC.4,5.
The combination of pre-habilitation and the application of High-Flow Nasal Cannula (HFNC) after OE has not been investigated yet.
This is a feasibility study evaluating a pre-habilitation program and the post-operative application of HFNC on PPC after OE.
We prospectively included patients undergoing OE from May 2021 to February 2022.
A preoperative multimodal prehabilitation program was applied to all patients.
Within 4 hours after surgery, patients were extubated and put under HFNC (50–60 lt/min with FIO2 0.4, humidifier temperature at 34°C) for the following 5 days. Chest physiotherapist applied daily post-operative respiratory exercise to all patients.
Hospital stay outcomes, feasibility of HFNC and PPC were recorded by 30 days after surgery.
We compared this group with an historic cohort (January 2016–March 2021) where HFNC was not applied to determine differences in baseline characteristics and post-operative complications.
We included 45 patients for the final analysis, 12 in the HFNC and 33 in the historic cohort. Baseline characteristics comparisons are shown in table 1.
No interruption of post-operative HFNC was recorded due to patient’s complain.
PPC in the two groups were statistically comparable. No adverse event was related to HFNC application. The overall leakage rate was 9%.
A prehabilitation program and HFNC use after OE seems feasible, safe and well tolerated by patients.
PPC were lower in the treatment group without statistically significant difference. Pneumonia was recorded in less than 20% of patients; in the study group there weren’t severe pulmonary complications (ARDS, reintubations).
HFNC looks like an interesting tool for post-operative respiratory support.
Larger randomized controlled trials should be designed to evaluate HFNC efficacy after esophagectomy.
268. COMPARISON OF OUTCOME OF GASTRIC TUBE RECONSTRUCTION FOR ESOPHAGEAL CANCER BETWEEN RECONSTRUCTIVE ROUTES
Authors: Tanaka Koji , Yamashita Kotaro , Makino Tomoki , Saitoh Takuro , Yamamoto Kazuyoshi , Takahashi Tsuyoshi , Kurokawa Yukinori , Nakajima Kiyokazu , Eguchi Hidetoshi , Doki Yuichiro 
Published: September 2022

Abstract
The route of gastric tube reconstruction after esophageal cancer resection is generally adopted as either posterior sternal or posterior mediastinal. There have been no large-scale comparative studies, and each institution has chosen a route based on its own experience. Therefore, we conducted an observational study at our institution to compare the postoperative outcomes of posterior sternal and posterior mediastinal reconstruction in gastric tube reconstruction for esophageal cancer.
The study included 159 patients with thoracic esophageal cancer who underwent subtotal esophagectomy and gastric tube reconstruction (73 patients in the posterior sternal reconstruction (RS) group and 86 patients in the posterior mediastinal reconstruction (PM) group) from 2016 to 2018 and compared perioperative and postoperative complications and postoperative nutritional status.
There were no differences in age, location, or pStage between the reconstructive routes, but BMI was significantly higher in RS (22.0 ± 2.9) and PM (20.8 ± 3.1). Anastomotic leakage (RS:PM = 8%:3%) and respiratory complications (RS:PM = 6%:15%) were not significantly different. PM was also significantly more common with ileus (13%). Anastomotic stenosis requiring dilation was significantly less common in PM than RS (31%:17%, p = 0.04). Weight loss was significantly higher in the RS group at 1 year postoperatively (RS/PM:13.9%/10.2%, p = 0.02). We have changed to PM with gastrostomy and the modified Collard anastomosis. These procedures have decreased the occurrence of ileus due to jejunostomy. Anastomotic stenosis was reduced to 5%.
In gastric tube reconstruction after subtotal esophageal resection for esophageal cancer, the reconstructive route (posterior sternal or posterior mediastinal route) showed no significant difference in the incidence of postoperative pneumonia or anastomotic leakage. By changing the anastomotic procedure, a decrease in anastomotic stenosis was observed even with posterior sternal reconstruction. We plan to accumulate more cases and investigate the effects on quality of life and nutritional status in the future.
269. PATIENT-DERIVED TUMOR ORGANOIDS AND XENOGRAFTS AS BASIC AND PRECLINICAL TRANSLATIONAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA MODELS
Authors: Yu Valen Zhuoyou , Lung Bryan Chee-chad , Wong Ian Yu-hong , Wong Claudia Lai-yin , Chan Desmond Kwan-kit , Chan Fion Siu-yin , Law Betty Tsz-ting , Law Simon , Lung Maria Li 
Published: September 2022

Abstract
Patient-derived xenografts have been gold standards for cancer modeling and drug testing. However, low establishment efficiency and high maintenance cost have hindered the development in the field. Recently, patient-derived tumor organoid (PDO) cultures have been developed as an efficient and economic model to mimic and recapitulate the original tumor tissue. Due to the limited availability of current esophageal squamous cell carcinoma (ESCC) models, we aimed to establish PDO cultures for ESCC study.
We have established and biobanked a panel of ESCC PDO cultures in vitro from Chinese ESCC treatment-naïve patients undergoing an endoscopic examination or upfront surgery, or patients undergoing neoadjuvant chemoradiotherapy (CRT) followed by surgery in Hong Kong. We also established and maintained a panel of PDO-derived xenograft (PDOX) in immunocompromised mice.
Genomic profiling showed consistent mutational landscapes of the established PDOs, as compared to ESCC patient profiles. Transcriptomic profiling suggests PDOs closely resemble patient tumor samples. In vitro chemotherapy treatments followed by prolonged recovery suggests the existence of a subpopulation of persistent cells likely enriched by neoadjuvant CRT and well-preserved by organoid cultivation. Coupled with live-cell bioluminescent-based quantification techniques, PDO cultures can be employed in high-throughput therapeutic screening. Immunohistochemical examination confirmed the squamous origin of the PDOs and PDOXs. Slow-proliferating PDOXs allow adequate interaction between the cancer cells and the host and are useful as a suitable preclinical drug testing platform.
ESCC PDOs can be efficiently established from highly limited patient tissue samples and maintained long-term in vitro and can be feasibly integrated with mouse models. ESCC PDOs and PDOXs serve as novel models for ESCC basic and translational studies.
270. SAFETY AND EFFICACY OF PREOPERATIVE FOLFOX FOR PATIENTS WITH RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA WHO ARE NOT CANDIDATES FOR CISPLATIN
Authors: Kadono Toru , Yamamoto Shun , Ohara Akihiro , Itoyama Mai , Yokoyama Kazuki , Honma Yoshitaka , Ishiyama Koshiro , Oguma Junya , Daiko Hiroyuki , Kato Ken 
Published: September 2022

Abstract
The standard preoperative treatment for resectable locally advanced esophageal squamous cell cancer (LAESCC) in Japan is a cisplatin (CDDP)-containing chemotherapy. However, patients with renal or cardiac dysfunction and elderly patients are not candidates for CDDP because of renal toxicity and the need for hydration. Oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX) therapy causes less renal toxicity and does not require hydration. We evaluated the preoperative FOLFOX therapy in patients who are unsuitable for CDDP remains unknown.
The subjects of this retrospective study were histologically confirmed LAESCC patients unsuitable for CDDP because of an age ≥ 75 years or a creatinine clearance (CCr) &lt;60 mL/min, or cardiac dysfunction who received preoperative FOLFOX therapy at our hospital between 2019 and 2021. Supraclavicular lymph node metastasis was considered resectable. Preoperative FOLFOX therapy (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and 5-fluorouracil 400 mg/m2 [bolus] plus 2400 mg/m2 [continuous] every 2 weeks) was administered for 3 or 4 courses. We evaluated adverse events during preoperative chemotherapy (CTCAE version 5.0), complete resection rate, and histopathological response.
Thirty-five patients were eligible for inclusion in the study (median age 77 years [range, 65–89]; performance status 0/1, 40%/60%; clinical stage I/II/III/IVB [only supraclavicular lymph node], 11%/29%/57%/3%). The reasons for selecting FOLFOX were renal dysfunction (74%), age ≥ 75 years (69%), and cardiac dysfunction (17%). Four patients (11.4%) discontinued chemotherapy because of progression (n = 2), febrile neutropenia (n = 1), or neutropenia (n = 1). The most common grade ≥ 3 adverse events were neutropenia (60%) and leucopenia (29%). 31 patients underwent surgery. The complete resection rate was 87% (27/31) and the pathological complete resection rate was 16% (5/31). There were no treatment-related deaths.
Preoperative FOLFOX therapy was well tolerated and showed promising short-term efficacy in patients with resectable LAESCC who were not candidates for CDDP.
278. SHORT- AND LONG-TERM OUTCOME AFTER UPFRONT SURGERY OR NEOADJUVANT CHEMOTHERAPY FOLLOWED BY SURGERY IN ELDERLY PATIENTS WITH RESECTABLE ESOPHAGEAL CANCER
Authors: Shimonosono Masataka , Sasaki Ken , Tsuruda Yusuke , Noda Masahiro , Tada Nobuhiro , Arigami Takaaki , Matsushita Daisuke , Ohtsuka Takao 
Published: September 2022

Abstract
In Japan, the standard therapeutic strategy for resectable advanced esophageal cancer (R-AEC) is neoadjuvant chemotherapy (NAC) followed by surgery. However, there is no strong evidence of the strategy for the elderly patients, thus the efficacy of NAC for the elderly patients with R-AEC remains controversial. Here we studied the efficacy of NAC for R-AEC in the patients aged 75 or older.
This study included the patients aged 75 or older who diagnosed with R-AEC and underwent esophagectomy in our institution from 2005 to 2021. Among the total of 59 cases with R-AEC, the cases who received neoadjuvant chemoradiotherapy or who had poor follow-up were excluded, and the remaining 42 cases were enrolled in this cohort. Among 42 patients with R-AEC, 33 patients underwent UFS and 9 patients underwent NAC followed by surgery. The short- and long-term outcome was evaluated between upfront surgery (UFS) group and NAC group.
There was a difference in historical background: patients in UFS group were more in 2012 or before, and patients in NAC group were more later than 2013. There was no significant differences in age, PS, Charlson comorbidity index and clinical characteristics such as TNM disease stage between two groups. The short-term outcome, the frequency of postoperative complications, curability, etc., was similar in two groups. In UFS group, only 5 cases (15.2%) underwent adjuvant chemotherapy. NAC improved 2-year RFS (UFS: 51.4% vs. NAC 76.2%, not significant), and 2-year OS (UFS 60.1% vs. NAC 71.1%, not significant).
This study showed the likelihood of the benefits of NAC on the long-term outcomes without increasing the postoperative complications in patients with R-AEC aged 75 or older. There were some limitations in this study, single-institutional and retrospective study with small number of cases. The further study will be needed to clarify the efficacy of NAC in elderly patients with R-AEC.
279. CLONAL RELATIONSHIP AND ALCOHOL CONSUMPTION-ASSOCIATED MUTATIONAL SIGNATURE IN SYNCHRONOUS HYPOPHARYNGEAL TUMORS AND ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Ko Josephine 
Published: September 2022

Abstract
The patients with dual esophageal squamous cell carcinoma (ESCC) and head and neck cancers have poor prognosis, but the underlying genetic pathogenesis is unclear. We hypothesize that independent origin rather than multifocality, which means local or lateral spreading involves the development of synchronous ESCC and hypopharyngeal cancer (HPC). We also hypothesize that multi-regional assessment provides better understanding of the evolution of tumor subclones and assessment of intra-tumor heterogeneity to guide personalized treatment with prognostic implications.
Multiple region whole-exome sequencing (M-WES) and clonality analysis were used to assess clonal relationship and spatial inter- or intra-tumor heterogeneity (ITH) in 62 tumor regions, six normal tissues, and 15 blood samples from eight dual ESCC/HPC and ten ESCC patients.
All synchronous ESCC/HPC patients had COSMIC 16 mutation signature compared to only 40% ESCC in the current study (p = 0.013) and public ESCC dataset (n = 165, p = 0.003). The mutational landscape and copy number variation (CNV) profiles were completely distinct between the ESCC/HPC; clonality analysis further suggested the two primary tumors shared no or only one clone accompanying independent subclone evolution. The M-WES strategy demonstrated higher sensitivity and accuracy for detection of mutational prevalence and the late branch mutations among different regions in the ESCC tumors compared to traditional single biopsy strategy. Patients with high ITH was significantly associated with both relapse and survival.
Our hypothesis-generating M-WES ITH assessment data have implications for prognostication. We are the first to show a distinctive CNV and genetic mutation profile, the predominant alcohol-related COSMIC 16 mutational signature in synchronous ESCC/HPC, providing genetic evidence for a multi-centric independent origin for clonal evolution and the theory of field cancerization implicating an etiologic role of alcohol metabolism in dual ESCC/HPC carcinogenesis.
280. MULTI-OMIC FEATURES OF OESOPHAGEAL ADENOCARCINOMA PATIENTS PRE-TREATED WITH PREOPERATIVE NEOADJUVANT THERAPY
Authors: Naeini Marjan , Newell Felicity , Aoude Lauren G , Bonazzi Vanessa F , Patel Kalpana , Lampe Guy , Koufariotis Lambros T , Lakis Vanessa , Addala Venkateswar , Kondrashova Olga , Johnston Rebecca L , Sharma Sowmya , Brosda Sandra , Holmes Oliver , Leonard Conrad , Wood Scott , Xu Qinying , Thomas Janine , Walpole Euan , Mai G Tao , Ackland Stephen P , Martin Jarad , Burge Matthew , Finch Robert , Karapetis Christos S , Shannon Jenny , Nott Louise , Bohmer Robert , Wilson Kate , Barnes Elizabeth , Zalcberg John R , Smithers B Mark , Simes John , Price Timothy , Gebski Val , Nones Katia , Watson David I , Pearson John V , Barbour Andrew P , Waddell Nicola 
Published: September 2022

Abstract
The incidence of oesophageal adenocarcinoma (OAC) is rising in Western countries, with a 5-year overall survival (OS) rate of 14%. Curative treatment based on oesophagectomy is only suitable for ~50% of patients due to late-stage diagnosis. While the addition of preoperative chemotherapy or chemoradiotherapy has improved OS in OAC patients, little is known about the molecular basis of treatment response and patient outcomes.
We investigated multi-omics data including whole-genome sequencing, RNA sequencing, methylation profiles and immunohistochemistry from 115 OAC patients mostly from DOCTOR phase II clinical trial that utilized neoadjuvant therapy (ANZCTR-ACTRN12609000665235).
We identified genomic features associated with poor OS, such as the APOBEC mutational signature. We also showed that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. RNA sequencing and methylation profiles suggested four immune clusters associated with OS and progression-free survival. The immune-suppressed cluster was associated with worse survival and epithelial-mesenchymal transition signature and enriched with myeloid-derived cells. The immune hot cluster was associated with better survival and enriched with T-cells, myeloid-derived cells, interferon-gamma and alpha responses, and immune markers such as CCL5, CD8A, and NKG7.
We investigated multi-omic features of OAC tumours from patients who were part of phase II clinical trial. We discovered prognostic features such as mutational signatures and complex genomic events. We identified distinct immune clusters associated with patient outcomes and the potential of immunotherapy for select clusters. We characterized molecular features of OAC patients which has the potential to predict responses to neoadjuvant therapy and develop better-selected therapy, monotherapy, or combination therapy in the future.