bluuebunny/crossref_metadata_2025 huggingface dataset:
135. A COMPARISON OF THE INOUE ASSESSMENT METHODS AND THE HILL GRADING OF THE GASTROESOPHAGEAL JUNCTION IN DIAGNOSING REFLUX SYMPTOM SEVERITY, ESOPHAGITIS, AND GERD AMONG PATIENTS WHO UNDERWENT UPPER GI ENDOSCOPY IN A TERTIARY HEALTHCARE FACILITY
Authors: Tan Michael Alek , Go Chris Jordan , So-Cabahug Jacklyn , Uy Karen Kaye , Sanchez Danica , Talingdan-Te Marilyn , Uy Manley
Published: September 2022

Gastroesophageal reflux disease (GERD) results from failure of the anti-reflux barriers in the gastroesophageal junction. Inoue proposed cardiac opening (CO), sliding hernia (SH), and scope holding time (SHT%) to assess this junction.

To compare these Inoue methods and the Hill grade in diagnosis of severe GERD symptoms, moderate–severe esophagitis and GERD.

Patients scheduled for gastroscopy off proton pump inhibitors were included. Symptoms were assessed using the GERDQ score. Esophagitis was determined using the modified LA Classification. The gastroesophageal junction was described using the Inoue methods and the Hill grade. The Inoue methods individually and as a composite score were compared to Hill grade.

We were unable to reach our target sample size of 91. Only 69 patients were included. In severe GERD symptom diagnosis (GERDQ ≥11), Inoue score (composed of CO and SH with 1 point each) had good performance (AUC 0.87, 95%CI 0.70–1.04). In moderate–severe esophagitis diagnosis (LA grades B-D), SH (AUC 0.73, 95%CI 0.58–0.88) and Inoue score (AUC 0.79, 95%CI 0.64–0.94) had fair performance. In GERD (either GERDQ ≥8 or esophagitis) diagnosis, Inoue score (AUC 0.88, 95%CI 0.80–0.97) and CO (AUC 0.76, 95%CI 0.63–0.89) had fair-good performance. The rest had poor or failed values.

Inoue score had fair-good performance in diagnosing severe GERD symptoms, moderate–severe esophagitis and GERD. Sliding hernia had fair performance in diagnosing moderate–severe esophagitis. CO had fair performance in diagnosing GERD. SHT% and Hill grade were poor/failed for all outcomes.
161. THE EFFECTIVENESS OF TELEPHONE AND INTERNET-BASED SUPPORTIVE CARE FOR PATIENTS WITH ESOPHAGEAL CANCER ON ENHANCED RECOVERY AFTER SURGERY IN CHINA
Authors: Yu Yuan
Published: September 2022

Esophageal cancer patients face problems related to eating and surgery-related symptoms. The eating-related problems are characterized by dysphagia, appetite loss, and nausea/vomiting linked to anatomic changes and the reconfiguration of their upper GI tract. Of all the surgery-related problems, 30% of patients reported fatigue/pain symptom cluster (pain, fatigue, insomnia, dyspnea), and 27% of patients reported the reflux/cough cluster (dry mouth, taste changes, cough, reflux). Evidence shows that the supportive care needs of esophageal cancer patients are very high.

The study was designed as an open-label, randomized controlled trial to value the efficacy of a nurse-led supportive care program in comparison with conventional care. The control group received conventional care. Patients from the intervention group received conventional care and one-on-one phone calls from nurses following their discharge assessments and education about nutrition and symptoms. Nurses also set up a WeChat group, which they invited patients to join in before discharge. Nutritional status, quality of life, the helpfulness of the follow-up service, and the patients’ satisfaction were compared 6 months after discharge to assess for differences between the two groups.

168 patients were included in the study, with 86 patients in the intervention group and 82 in the control group. Significant differences between the intervention and control groups were found in the Nutrition Risk Screening 2002 and simple diet self-assessment tool scores. The changes in blood albumin, prealbumin, and transferrin were also statistically significant. All QLQ-C30 results of the intervention group were better than those of the control group. The patients’ scores on the helpfulness of the follow-up service and their satisfaction with it were both significantly higher in the intervention group than in the control group.

This study highlighted the important role of nurse-led supportive care based on telephone and Internet-based support for patients after ERAS. The supportive care improved patients’ nutritional status, elevated their quality of life, and improved their satisfaction with the care provided to them.
207. THE EVOLUTION OF THE PERIOPERATIVE ENHANCED RECOVERY PROTOCOL IN ESOPHAGEAL SURGERY DURING 10 YEARS
Authors: Yan Maria , Ruchkin Dmitry
Published: September 2022

The perioperative enhanced recovery protocol routinely uses in esophageal surgery. It acquired new aspects which were adapted to reduce the rate of morbidity and mortality. Esophagectomy still remains a high-risk operation, which carries out in high-volume centers on patients with significant comorbidities. It challenges the multidisciplinary team to personalize approach to create a safe recovery after surgery. The objective of the study is to show the aspects of evolution of the protocol after esophageal surgery.

A total 393 patients with benign and malignant esophageal diseases underwent esophagectomy with simultaneous reconstruction between December 2012 and December 2021. The median age was 59 years (47;67), females were 39,7% and males—60,3%. The prevalence of the patient with nutritional deficiency was 20% (BIM < 18.5) and ASA score III-IV—66,9%. The tranthoracic and transhiatal esophagectomy were used for 42,2% and 57,8% of patients with the reconstruction by gastric pull up (92,1%), colon conduit (6,4%), jejunal loop interpostion with gastric pull-up 1% and with colon conduit 0,5%.

169 patients (43%) had postoperative complications, while 28,9% of them had one complication and 3,6% more than 4 complications at the same time. The prevalence of complications: pneumonia—8,2%, atrial dysrhythmia requiring intervention—7,7%, pulmonary embolism—1%, acute renal failure requiring dialysis—1,5%. The anastomotic leak occured in 5,4% patients and conduit necrosis—in 2,8% (2,3% extensive) patients. The prevalence of patients required repeated surgery was 6,4%. The rate of severe complications (>IIIb- Clavien-Dindo) was 14,4%. Median postoperative day was 9 (8;11). The postoperative mortality rate 1,8%.

The aspects of the perioperative enhanced recovery protocol were modified to complicated surgery with simultaneous resection of other organs, esophagogastrectomy or reconstruction by combined conduit with jejunal loop with early oral feeding and rapid recovery. The decade-long experience of the evolution of the perioperative enhanced recovery protocol has led to the development of the personalized approach to the patients with significant comorbidities that allowed reducing the incidence of postoperative complications and mortality after esophagectomy.
221. ANASTOMOTIC LEAK AFTER A CARDIO-OESOPHAGECTOMY: A RETROSPECTIVE 12 YEAR EXPERIENCE OF A TERTIARY CENTRE
Authors: Chaudhury Madhu , Singh Mohan , Shetty Vinutha , Ball Chris , Ward Jeremy , Turner Paul , Pursnani Kishore
Published: September 2022

Anastomotic leak (AL) post cardio-oesophagectomy remains a significant complication which can impact morbidity and mortality. Incidences of anastomotic leakage after oesophagectomy range between 0 and 20%. Current clinical practice is driven by regional centres and anecdotal experience. We present our 12 year experience with managing patients with anastomotic leaks.

This was a retrospective study using the electronic database to analyse the incidence of anastomotic leak in consecutive patients who underwent elective cardio-oesophagectomy from April 2009 to December 2021 in a Tertiary Upper GI cancer centre. The grade of the AL was determined according to the Clavien-Dindo Grade (CDG). A leak associated with Grade > III was categorised as severe anastomotic leak. We used Cox multivariable analysis to observe any link in the severity of the anastomotic leak and prognosis.

A total of 560 patients underwent cardio-oesophagectomy. The median length of stay was 13 (Range 3 to 148 days) days and the median age was 66 (46–79) years. M/F 2:1. AL was seen in 26 cases (4.3%); of which 9 cases (0.7%) were classified as severe AL (CDG > 3). Our results are presented on the table attached. Statistical analysis does not show any link between the severity of the anastomotic leak, those who had neoadjuvant therapy and the survival outcome.

Anastomotic leaks of all grades prolongs both ITU and hospital stay. This subsequently causes delays in adjuvant therapies affecting long term prognosis. Aggressive treatment early on for large leaks suggests no significant compromise on over-all long-term prognosis.
236. TH1 CELL IS THE KEY IMMUNE-ASSOCIATED PREDICTOR OF PATHOLOGICAL COMPLETE RESPONSE FOLLOWING NEOADJUVANT CHEMORADIATION FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Yuan Jianye , Weng Zelin , Xie Xiuying , Wen Jing , Fu Jianhua
Published: September 2022

Neoadjuvant chemoradiation followed by surgery is recommended for locally advanced esophageal squamous cell carcinoma (ESCC). Patients achieve pathological complete response (pCR) have better survival outcomes. Immune cells in tumor microenvironment (TME) are potential to affect chemoradiation sensitivity. Our study aimed to discover key immune-associated predictors of pCR for ESCC.

The infiltrations of multiple immune cells were estimated by ImmuCellAI and cibersort based on RNA-seq data of fifty ESCC samples before treatment. The infiltrations of immune cells including Th1 cells, CD3+ T cells, CD8+ T cells, NK cells, NKT cells and DCs were evaluated by multiplex immunohistochemistry (mIHC) in 131 ESCC samples before treatment. In-vitro cell experiments were performed to discover the effects of Th1 cells on tumor cells.

The analysis of RNA-seq data of ESCC revealed that the infiltration of Th1 cells was higher in pCR group. Results of mIHC demonstrated that infiltrations of Th1 cells and its relevant immune cells including CD8+ T cells, NK cells, NKT cells and DCs were positively associated with pCR. ESCC samples were divided into two subtypes based on the infiltration of these immune cells, with the high infiltration subtype was easier to achieve pCR. In-vitro cell experiments confirmed that Th1 cells were able to inhibit proliferation and improve chemoradiation sensitivity of tumor cells.

Infiltrations of Th1 cells and its relevant immune cells are positively associated with pCR following neoadjuvant chemoradiation in ESCC. Th1 cells can improve the chemoradiation sensitivity of tumor cells.
240. PERIOPERATIVE OUTCOME AND SURGICAL TECHNIQUE OF TRANSMEDIASTINAL ESOPHAGECTOMY FOR ESOPHAGOGASTRIC JUNCTION CANCER
Authors: Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hirotaka , Ohashi Takuma , Shimizu Hiroki , Arita Tomohiro , Yamamoto Yusuke , Morimura Ryo , Kuriu Yoshiaki , Ikoma Hisashi , Kubota Takeshi , Otsuji Eigo
Published: September 2022

We started performing mediastinal lymph node dissection by a laparoscopic transhiatal approach (LTHA) in 2009. To date, 463 patients had undergone our method during various esophageal surgical procedures, including esophagogastric junction cancer (EGJC). Furthermore, we started performing single-port mediastinoscopic cervical approach in 2014, and developed a simple technique for transmediastinal esophagectomy (TME) without thoracic approach (350 cases). Fifty four patients with EGJC were treated by TME.

Left single-port mediastinoscopic cervical approach was performed with pneumomediastinum. Mainly for advanced SCC, upper mediastinal lymph node dissection including recurrent laryngeal nerve LNs was performed with intraoperative monitoring using NIM system. Next, LTHA was performed for en bloc mediastinal lymph node dissection. The esophageal hiatus was opened, and working space was secured by Long Retractors. The posterior plane of the pericardium was extended. The posterior side of LNs was then separated. Finally, while lifting LNs like a membrane, they were resected from bilateral mediastinal pleura. Reconstruction with narrow gastric conduit was performed through substernal tract.

Patients with EGJC performed TME were analyzed (n = 54, SCC/Adeno/Others = 29/23/2). Upper mediastinal lymph node metastasis was found in 9 cases (SCC/Adeno = 5/4), middle mediastinal lymph node metastasis was found in 5 cases (SCC/Adeno = 3/2), and all of them had advanced tumors. Their perioperative outcome were compared with those performed the right thoracotomy (n = 41). The operative time and bleeding were decreased by TME. The number of resected mediastinal lymph nodes, pR0 rate, and mediastinal recurrence in the two groups were not different. In 92.6% of patients treated by TME, extubation was performed at 0 POD. Postoperative respiratory complications was decreased by TME (TME:7.4%, thoracotomy:17.1%).

This procedure, TME, resulted in a good surgical view, safe en-bloc mediastinal lymph node dissection, and the decrease of postoperative respiratory complications in patients with EGJC.
244. EXPLORING THE OPTIMAL STARTING AGE FOR ESOPHAGEAL CANCER SCREENING BASED ON DATA FROM A MULTICENTER POPULATIONS-BASED COHORT AND CANCER REGISTRY
Authors: Chen Ru , Dou Lizhou , Zhou Jiachen , Song Guohui , Li Bianyun , Zhao Deli , Hua Zhaolai , Wang Xinzheng , Li Jun , Hao Changqing , Li Yanyan , Feng Xiang , Li Lin , Wei Wenqiang , Wang Guiqi
Published: September 2022

Although endoscopic screening has been proven to be effective in reducing the incidence and mortality of esophageal cancer, evidence is limited on the determination of starting age for individuals participating in the screening. The aim of this study is to provide evidence-based recommendations on starting age for esophageal cancer screening.

We used the data from a multicenter prospective screening cohort in high-risk areas of esophageal cancer in China to explore the starting age of population-based screening. The target population was all permanent residents aged between 40 and 69 years from six centers. The hazard ratio (HR) with 95% confidence interval (CI) and number needed to screen (NNS) were compared between the screened group and the unscreened group in different age groups. The starting age of opportunistic screening for general population was analyzed based on the incidence and mortality of esophageal cancer estimated from cancer registry.

The cohort analyzed in this study consisted 113340 screened and 224677 unscreened subjects. Compared with the unscreened group, significant reductions were observed in incidence and mortality in all age groups in the screened group except for the incidence in the 40–49 age group (HR = 0.94, 95%CI:0.79–1.13). There were large gaps in the effectiveness of screening for different age groups. The NNS to prevent one esophageal cancer death was 769, 198 and 63 in the 40–49, 50–59 and 60–69 age groups, respectively. Incidence and mortality of esophageal cancer in the general population attained the average at the age of 50–54 years.

Postponing the starting age of endoscopic screening to 50 years might improve the effectiveness of screening in high-risk areas. Individuals with general risk could take their first endoscopic screening at the age of 50–54 years.
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

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 < 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

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

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 = <0.001, <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

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

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

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

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) <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

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

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

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.
282. VALIDITY AND RELIABILITY OF CROWD-SOURCED AND EXPERT VIDEO ASSESSMENT IN MINIMALLY INVASIVE ESOPHAGECTOMY USING GLOBAL RATING SCALES
Authors: Ketel Mirte , Klarenbeek Bastiaan , Eddahchouri Yassin ,   MIE-GOALS Collaboration Group, Abma Inger , Rosman Camiel , van Workum Frans
Published: September 2022

Minimally Invasive Esophagectomy (MIE) is a complex and technically demanding procedure and implementation is associated with a substantial learning curve. Suboptimal surgical performance in complex minimally invasive procedures has convincingly been related to less favorable patient outcomes. Structured video-based assessment by other surgeons can objectively evaluate surgical performance, but requires a surgeon’s scarce time. This study investigated whether crowdsourcing, collective surgical performance evaluation by anonymous and untrained laypeople, could be a valid alternative for MIE.

Two video assessments types were conducted via the C-SATS platform with eight MIE operative videos. First, videos were cut into eight procedural phase-based video clips of maximum ten minutes. These 64 video clips were assessed with the validated Global Operative Assessment of Laparoscopic Skills (GOALS)‘s four domains (depth perception, bimanual dexterity, efficiency and tissue handling) using a 1-5 Likert scale. Each video clip was assessed by a pair of two MIE experts and > 30 crowd workers, recruited via Amazon Mechanical Turk. Second, the same expert pairs assessed the corresponding complete video with the procedure-specific MIE competency assessment tool (MIE-CAT).

Experts assessed 128 clips and sixteen complete videos in 3.5 months. Crowd workers assessed 1984 clips in < two days. Expert scores showed a wider range (expert GOALS score range 7.50-19.50 versus 12.84-15.63 for crowds). When comparing experts and crowd workers scores, a poor correlation was found on all domains and total GOALS scores (ICC ≤ 0.42). When correlating GOALS scores with MIE-CAT scores a strong, positive correlation between experts’ scores was found (r¬s = 0.76, p = 0.03) while between crowd’s GOALS and expert’s MIE-CAT scores a small correlation was found (r¬s = 0.23, p = 0.58) (Figure 1).

Despite rapid results from crowd workers, a poor agreement between crowd and experts’ GOALS scores was observed. MIE might be technically too difficult to assess for laypeople. Furthermore, GOALS might not be extensive enough to assess MIE performance in detail, while the procedure-specific MIE-CAT might be more comprehensive. However, the correlation between the experts’ MIE-CAT and GOALS scores indicates video clip assessments (instead of full length video assessments) could be helpful to shorten assessment time.
286. THORACOPHRENOLAPAROMY FOR SURGICAL TREATMENT OF GEJ CANCER
Authors: Garbarino Giovanni Maria , Eshuis Wietse J , Daams Freek , van Berge Henegouwen Mark I , Gisbertz Suzanne S
Published: September 2022

Nowadays, there is still a lack of consensus about the optimal surgical management of gastroesophageal junction (GEJ) tumor. The CARDIA-trial results, comparing transthoracic esophagectomy versus transhiatal extended gastrectomy for GEJ type II tumor, are still expected. Thoracophrenolaparotomy (TPL) allows to perform radical resections (higher rate of R0 and more extensive mediastinal lymphadenectomy) with both esophago-gastric or esophago-jejunal anastomoses. The aim of this study is to describe TPL for the treatment of GEJ and gastric cancer.

A retrospective analysis of all TPL performed for GEJ and gastric cancer with esophageal involvement at the Amsterdam UMC from January 2019 to October 2021 was conducted. The primary endpoint was the evaluation of R1 resections. The secondary endpoints were postoperative and pathological outcomes.

Forty-seven patients were included for the analysis. 18 patients underwent an esophago-cardia resection with gastric conduit reconstruction and 29 patients a total gastrectomy with distal esophagectomy. The main indications for TPL were cT3 (74.5%) and cN+ (55.3%) tumors. Postoperative pneumonia occurred in 4 (8.5%) patients and anastomotic leak in 2 (4.3%) patients. The mean hospital stay was 9.8 (±6.1) days. The mean tumor size was 42.3 (±32.8) mm and the mean proximal margin 31.0 (±20.7) mm. Two (4.3%)patients had a R1 resection of whom only one (2.1%) had a positive proximal margin. The mean number of retrieved lymph nodes was 31.6 (±9.9).

Thoracophrenolaparotomy for selected patients with GEJ and gastric cancer is associated with high R0 resection rate, low pneumonia and anastomotic leak incidence, together with a short hospital stay. TPL should still be considered a reliable surgical option, even in high-volume centers for minimally invasive upper gastrointestinal surgery.
291. A CASE OF LAPAROSCOPIC AND THORACOSCOPIC ENUCLEATION FOR GIANT CIRCUMFERENTIAL ESOPHAGEAL LEIOMYOMA
Authors: Sato Kazuhide , Masuda Takahiro , Tanishima Yuichiro , Fujisaki Muneharu , Uno Koei , Hara Keigo , Takahashi Keita , Yano Fumiaki , Eto Ken
Published: September 2022

Enucleation is surgically or endoscopically performed for submucosal tumors of the esophagus, especially for esophageal leiomyoma. Enucleation for large and circumferential tumors is technically challenging given a higher risk of mucosal injury and/or tumor rupture during procedure. We present a case of giant leiomyoma with a maximal diameter of 8 cm successfully enucleated by laparoscopic and thoracoscopic approaches.

A 24-year-old man was referred to our hospital with a mediastinal tumor suspected on chest X-ray. He suffered from heartburn for more than 10 years and recently dysphagia. Endoscopic examination revealed esophageal submucosal tumors located at 30 cm to 35 cm from the incisor, involving whole luminal circumference. Boring biopsies were endoscopically performed of which pathological diagnosis was esophageal leiomyoma. CT showed wall thickening in the lower esophagus with a maximal esophageal diameter of 8 cm.

Giant esophageal tumor enucleation with antireflux fundoplication was performed using both laparoscopy and thoracoscopy. The tumor expanded circumferential shape with the longitudinal extent of approximately 8 cm. After tumor enucleation, the esophageal mucosa was circumferentially exposed from the level of the azygos vein to the esophagogastric junction without the muscle layer. The esophageal mucosal injury occurred in 3 places, which were repaired by primary closure using absorbable threads. The operation time was 827 minutes and the loss of blood was 230 mL. The specimen was 160 g, and the final pathological diagnosis was leiomyoma. Postoperative course was not eventful.

We experienced a case of enucleation for a giant esophageal circumferential submucosal tumor. Enucleation may be considered a possible treatment strategy to avoid esophagectomy even for a giant circumferential tumor especially in young patients.
292. ROLE OF PREOPERATIVE NEOADJUVANT CHEMORADIOTHERAPY FOR LOCALLY ADVANCED BORDERLINE RESECTABLE THORACIC ESOPHAGEAL CANCER
Authors: Wakita Akiyuki , Motoyama Satoru , Sato Yusuke , Fujita Hiromu , Kemuriyama Kohei , Hayashi Kenjiro , Minamiya Yoshihiro
Published: September 2022

The results of the JCOG1109 trial indicate that the standard preoperative neoadjuvant therapy is Docetaxel-cisplatin-fluorouracil (DCF) combined chemotherapy. However, appropriate preoperative treatment for borderline resectable cases is still controversial. Preoperative CF-RT therapy with more substantial local control continues to be an option for tumors with a high risk of invading adjacent organs.

The study participants were 163 cT3 locally advanced thoracic esophageal cancer patients who underwent preoperative CF-RT therapy followed by radical esophagectomy. The patients were partitioned into 58 borderline resectable cases (cT3.5 group) and 105 resectable cases (cT3 group). We compared the clinicopathological features, surgical results, and survival between the two groups to verify the effectiveness of preoperative CF-RT therapy for cT3.5 cases.

SCC was the predominant cancer histological type. Significantly more upper and middle mediastinum cases and fewer lower mediastinum cases in the cT3.5 group (p < 0.0001). There were no significant differences in postoperative complications; anastomotic leakage was 12.1%, and recurrent laryngeal nerve palsy was 32.8%. The pCR rate was significantly lower in the cT3.5 group (p = 0.0219). Nineteen patients (32.8%) in the cT3.5 group relapsed. Details of recurrence were locoregional in 7 patients, distant LN in 1 patient, and distant organ in 11 patients. There were no significant differences in neither 5-year OS nor 5-year DFS between the two groups (p = 0.6547, p = 0.8799; respectively).

Borderline resectable esophageal cancer (cT3.5) treated with preoperative CF-RT therapy showed a comparable survival rate even though the pCR rate was lower than that of resectable esophageal cancer (cT3). Preoperative CF-RT therapy may still be a promising treatment for locally advanced thoracic esophageal cancer with suspected invasion of adjacent organs.
307. INGENUITY OF ESOPHAGOGASTRIC ANASTOMOSIS IN OUR DEPARTMENT -RECONSTRUCTED GASTRIC TUBE STUMP CLOSURE USING ENDO GIA RADIAL RELOAD
Authors: Hirahara Noriyuki , Matsubara Takeshi , Hayashi Hikota , Yamamoto Tetsu , Hyakudomi Ryoji , Tajima Yoshitsugu
Published: September 2022

Anastomotic leakage is one of the three major complications after esophagectomy and can lead to surgery-related death. In our department, the standard surgical procedure is to elevate the gastric conduit via the posterior mediastinal pathway, and end-to-side anastomosis using a circular stapler for the residual esophagus and gastric conduit. In this study, we will report our reconstruction method and ingenuity, since Linear stapler was changed to Endo GIA Radial Reload and better outcomes were delivered.

The lesser curvature of the gastric conduit stump is the site where blood flow is most reduced. When the gastric conduit stump is closed with Linear stapler, the blood flow may be further reduced, because the stapler on the lesser curvature of the gastric conduit and the stapler on gastric conduit stump intersect. Closing the gastric conduit stump using Radial Reload avoids the stapler intersect at the lesser curvature and the gastric conduit stump. In addition, since a natural curve is formed at the gastric conduit stump, the pressure applied to the gastric tube stump by coughing can be dispersed.

Nine patients have undergone this reconstruction method, and no anastomotic leakage has been observed.

It is important to constantly evaluate one’s own surgical technique, and to continue developing the surgical technique for further safety by making improvements.