bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of synchronous robot motion on human synchrony and enjoyment perception
Authors: Meneses Alexis , Yoshikawa Yuichiro , Ishiguro Hiroshi
Published: September 2021

Enhancing synchronization among people when synchronization is lacking is believed to improve their social skills,
learning processes, and proficiency in musical rhythmic development. Greater synchronization among people can be induced to
improve the rhythmic interaction of a system with multiple dancing robots that dance to a drum beat. A series of experiments were
conducted to examine the human–human synchrony between persons that participated in musical sessions with robots. In this study,
we evaluated: (a) the effect of the number of robots on a subject’s ability to synchronize with an experimenter; (b) the effect of
the type of robot synchrony, namely, whether the robots did or did not represent the subject’s rhythm; (c) the effect of an
in-sync and out-of-sync robot on a subject’s behavior. We found that: (a) three robots increased the level of synchronization
between the subject and experimenter and their enjoyment level; (b) robots may induce greater synchronization between the subject
and experimenter by reproducing the rhythms of not only the experimenter but also of the subject compared to when only the
experimenter’s rhythms had been reproduced; (c) the robots in-sync had greater influence on the natural rhythm of the subject.
Robots as an interactive-social medium in storytelling to multiple children
Authors: Tamura Yumiko , Shiomi Masahiro , Kimoto Mitsuhiko , Iio Takamasa , Shimohara Katsunori , Hagita Norihiro
Published: September 2021

This paper investigates the effects of group interaction in a storytelling situation for children using two robots: a reader robot and a listener robot as a side-participant. We developed a storytelling system that consists of a reader robot, a listener robot, a display, a gaze model, a depth sensor, and a human operator who responds and provides easily understandable answers to the children’s questions. We experimentally investigated the effects of using a listener robot and either one or two children during a storytelling situation on the children’s preferences and their speech activities. Our experimental results showed that the children preferred storytelling with the listener robot. Although two children obviously produced more speech than one child, the listener robot discouraged the children’s speech regardless of whether one or two were listening.
Do 12-month-old infants maintain expectations of contingent or non-contingent responding based on prior experiences
with unfamiliar and familiar adults?
Authors: Stenberg Gunilla
Published: September 2021

The current study examined whether infants use previous encounters for maintaining expectations for adults’
contingent responding. An unfamiliar adult responded contingently or non-contingently to infant signaling during an initial play
situation and 10 min later presented an ambiguous toy while providing positive information (Experiment 1; forty-two
12-month-olds). The infants in the contingent group looked more at the adult during toy presentation and played more with the toy
during the concluding free-play situation than the infants in the non-contingent group. When the parent had responded contingently
or non-contingently to infant bids (Experiment 2; forty 12-month-olds), the infants in the contingent group tended to look more at
the parent and tended to play more with the toy than did the infants in the non-contingent group. The results indicate that from
just a brief exposure, infants form expectations about adults’ responsiveness and maintain these expectations of
contingent/non-contingent responding from one situation to another.
Dysfunction along the continuum of vestibulocochlear anatomy, and the corresponding spectrum of clinical presentation
Authors: Cherchi Marcello , Yacovino Darío Andrés
Published: September 2021

Objective:

Explore how the terminology of some vestibulocochlear diseases leads to a misleading nosology that probably misrepresents the underlying neuroanatomy and pathology.

Methods:

Review what is known and unknown about neuroanatomical localization of some common vestibulocochlear diseases.

Results:

Literature on this topic often conveys, or strongly implies, discreteness of neuroanatomical localization and corresponding deficits, when in fact several common vestibulocochlear disorders are more likely to involve a continuum both in anatomy and in clinical presentation.

Conclusion:

Having recognized the misleading nature of the common classifications of these diseases, we suggest several strategies for improving diagnosis. Some of these suggestions are immediately applicable to the practice of vestibular medicine; others have potential relevance for emerging and future therapeutics.
Development and Validation of a UPLC–MS/MS Method for Ultra-Trace Level Determination of Acyl Chloride Potential Genotoxic Impurity in Mezlocillin
Authors: Chen Yuanqiu , Huang Lianzhou , Yuan Xiao , Luo Feng , Pu Hanlin
Published: September 2021

3-Chlorocarbonyl-1-methanesulfonyl-2-imidazolidinone (CMI) is a critical intermediate used in the synthesis of mezlocillin drug substance and also a potential genotoxic impurity with acyl chloride moiety. The content of CMI in mezlocillin should be <0.16 ppm to avoid the carcinogenicity and mutagenicity threats to patients. Therefore, a workable determination of CMI was critically crucial for ensuring the safety of mezlocillin drug products. However, the conventional HPLC method is insufficient for detection limits at ppm or lower levels. Besides, the high activity of acyl chloride also raises a challenge to the direct measurement of CMI. Thus, we explored a simple esterification approach, which converts CMI into methyl 3-(methylonyl)-2-oxoimidazolidine-1-carboxylate completely by optimizing the reaction temperature and time. Furthermore, the selected reaction monitoring model of triple quadrupole mass spectrometer optimized by the Box–Behnken design significantly enhanced the sensitivity of ultra-trace level determination. The limit of detection and limit of quantification of the method were reached 0.014 and 0.02 ppm, respectively, in the following validation study. A sensitive and specific ultra-performance liquid chromatography tandem mass spectrometry method for ultra-trace level determination of acyl chloride potential genotoxic impurity in mezlocillin drug substance has been successfully established in this study, which will provide a practical quality control tool of mezlocillin.
Group Companies and Climate Justice
Authors: Benjamin Lisa
Published: September 2021

A string of corporate litigation cases in the United Kingdom highlights the role of corporate group structures in complicating efforts to impose liability on parent companies for the activities of their subsidiaries, particularly where those subsidiaries are located in the Global South. Corporate group structures serve to insulate parent companies against liability for actions of their subsidiaries. This is the case even where economic benefits accrue to parent companies, which are often incorporated in the Global North. These group structures cabin liability for environmental and climate harms within subsidiary companies through reliance on company law principles such as limited liability and separate legal personality. These company law principles allow parent companies to enjoy corporate profits from the activities of their subsidiaries but disavow liability for any environmental damage resulting from such activities. This dichotomy has obvious equity implications, which are exacerbated in the extractive industries and in the context of climate change.

Negative climate impacts are and will be felt predominantly in the Global South. In addition, environmental damage removes avenues of climate adaptation for vulnerable populations. But company law principles are not impervious to these equity challenges. These principles have never been absolute and courts have consistently found exceptions to them, although those exceptions have fluctuated in effectiveness and frequency over the years. Recent decisions by the Court of Appeal and Supreme Court in the United Kingdom imposed duties on parent companies for environmental damage caused by their subsidiaries. Cases following the decision in Chandler v Cape Industries illustrate tension between company law as interpreted in the Global North, and climate and environmental justice as experienced in the Global South. Climate change forces a reconceptualization of company law, including transnational corporate liability. This paper argues that these reconsiderations are not only appropriate, but given the contested histories of many of these companies in the Global South, long overdue.
Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications
Authors: Gawałko Monika , Agbaedeng Thomas A , Saljic Arnela , Müller Dominik N , Wilck Nicola , Schnabel Renate , Penders John , Rienstra Michiel , van Gelder Isabelle , Jespersen Thomas , Schotten Ulrich , Crijns Harry J G M , Kalman Jonathan M , Sanders Prashanthan , Nattel Stanley , Dobrev Dobromir , Linz Dominik
Published: September 2021

Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. In this review, we discuss the evidence suggesting a potential bidirectional association between AF and gut microbiota, identifying gut microbiota-derived metabolites as possible regulators of the AF substrate. We summarize the effect of gut microbiota on the development and progression of AF risk factors, including heart failure, hypertension, obesity, and coronary artery disease. We also discuss the potential anti-arrhythmic effects of pharmacological and diet-induced modifications of gut microbiota composition, which may modulate and prevent the progression to AF. Finally, we highlight important gaps in knowledge and areas requiring future investigation. Although data supporting a direct relationship between gut microbiota and AF are very limited at the present time, emerging preclinical and clinical research dealing with mechanistic interactions between gut microbiota and AF is important as it may lead to new insights into AF pathophysiology and the discovery of novel therapeutic targets for AF.
151 A RANDOMIZED,OPEN CLINICAL TRIAL TO COMPARE THE EFFICACY AND SAFETY OF ANLOTINIB PLUS IRINOTECAN VERSUS IRINOTECAN IN PATIENTS WITH ESCC
Authors: Wang Feng , Meng Xiangrui , Liu Hangrui , Fan Qingxia
Published: September 2021

The benefit of systemic treatment in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain. Anlotinib (AL3818) is a novel multi-target TKI, inhibiting tumor angiogenesis and proliferation. A phase II trial (NCT02649361) has demonstrated that anlotinib has a durable antitumor activity with a manageable adverse event profile in refractory metastatic ESCC. This study (NCT03387904) aimed at comparing the effects and safety of Anlotinib Plus Irinotecan versus Irinotecan in patients with ESCC.

Methods

We conducted a prospective randomized, multicenter, phase II trial to compare the efficacy of Anlotinib Plus Irinotecan with Irinotecan in recurrent ESCC patients who had resistance to platinum or taxane-based chemotherapy. Eligible patients were adults with pathologically confirmed recurrent ESCC, and 82 patients were randomized 1:1 to Irinotecan (65 mg/m2/day 1 and day 8) with or without anlotinib (12 mg qd day 1 to 14) of a 21-day cycle till progression or intolerable. The primary endpoint is the disease control rate (DCR) and progression-free survival (PFS) and the secondary end points are objective response rate (ORR) and overall survival (OS).

Results

Between 13/1 2019 and 20/1 2020, a total of 43 patients were enrolled and randomly assigned to either the anlotinib plus irinotecan (n = 22) or the irinotecan group (n = 21).The mPFS was longer in trial group than in control group (89 days vs 66 days, HR = 0.447, P = 0.055). The Disease control rate (DCR) was 54.5% in trial group and 38.1% in the control group. The treatment-related adverse events (>10%) were fatigue (59.1%), nausea (50.0%), decreased appetite (36.4%), hoarseness (27.3%), thyroid-stimulating hormone elevation (22.7%), diarrhea (9.1%), and decreased lymphocytes count(9.1%) in trial group. Grade 3 AEs included fatigue (4.5% vs 4.8%), nausea (4.5% vs 0%) and diarrhea (4.5% vs 0%) in two groups.

Conclusion

Anlotinib plus irinotecan was similarly tolerable but prolonged PFS compared to irinotecan monotherapy as a second-line treatment in patients with recurrent ESCC.
156 THE EXPRESSION AND ROLE OF ANO9 IN HUMAN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Inoue Hiroyuki , Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hirotaka , Katsurahara Keita , Kudou Michihiro , Shimizu Hiroki , Arita Tomohiro , Kosuga Toshiyuki , Morimura Ryo , Kuriu Yoshiaki , Ikoma Hisashi , Kubota Takeshi , Okamoto Kazuma , Otsuji Eigo
Published: September 2021

The anoctamin (ANO) family consists of transmembrane proteins in 10 isoforms, and ANOs are broadly expressed in epithelial and non-epithelial tissues. Few studies have reported the function and activation mechanism of ANO9 in esophageal squamous cell carcinoma (ESCC), and the clinical significance of its expression remains unclear. The aims of the present study were to investigate the role of ANO9 in the regulation of tumor progression and its clinicopathological significance in ESCC.

Methods

In human ESCC cell lines KYSE150 and KYSE790, knockdown experiments were performed using ANO9 siRNA, and the effects on cell proliferation, cell cycle, apoptosis, invasion and migration were analyzed. The gene expression profiles of cells were examined using a microarray analysis. Immunohistochemical (IHC) analysis was performed on 57 primary tumor samples obtained from ESCC patients who underwent curative esophagectomy between 1999 and 2009 in Kyoto Prefectural University of Medicine.

Results

In an in vitro study, the depletion of ANO9 reduced cell proliferation, invasion and migration in KYSE150 and KYSE 790 cells. And, the depletion of ANO9 increased the number of cells in G0/G1 arrest and induced apoptosis in these cells. The results of the microarray analysis indicated that various centrosome-related genes such as CEP120, CNTRL and SPAST, were up- or down-regulated in ANO9-depleted KYSE150 cells. The IHC results showed that high expression of ANO9 was independent prognostic factor in ESCC patients (p = 0.025).

Conclusion

ANO9 played the important role in the cell cycle and progression of ESCC cells through the expression of centrosome-related genes. In addition, the high expression of ANO9 was a poor prognostic factor in ESCC patients. The results of the present study indicate that ANO9 has potential as a biomarker for cancer growth and as a therapeutic target for ESCC such as inhibitor or RNA interference of ANO9.
159 METFORMIN DOWNREGULATES PD-L1 EXPRESSION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA BY INHIBITING IL-6 SIGNALING PATHWAY
Authors: Wang Feng , Xin Dao , Meng Xiangrui , Fan Qingxia
Published: September 2021

ESCC is an aggressive cancer with poor prognosis in China. Metformin with low cost and toxicity have proved to have anti-cancer effects in many kinds of cancers, while its role in combination of immune checkpoint blockade and mechanism in ESCC has seldom been studied. This study was designed to evaluate the potential role of combinatorial anti-tumor effect with metformin and immunomodulatory monoclonal antibodies (mAbs) targeting programmed cell death protein-1 (PD-1) in vitro and in vivo.

Methods

Reverse transcription-quantitative polymerase chain reaction, western blot and immunohistochemistry (IHC) assays were used to study the effects of metformin on the expression levels of PD-L1. In addition, T cell activation and killing assay were performed in the co-culture system of ESCC cell and peripheral blood mononuclear cells (PBMCs) treated with metformin or IL-6 to evaluate the function of inhibiting PD-L1 expression. In vivo assay, we used NPIdKOTM mice model, which was re-constructed replaced immune system by transplanting PBMCs through intravenously injecting. Mice were treated with metformin alone as well as in combination with anti-PD-1 mAbs.

Results

PD-L1 expression were downregulated by metformin via JAK2 and STAT3 signaling pathway. The results showed that metformin promoted CD3/CD28 induced ERK phosphorylation at a dose dependent measure. And IL-2 was increased in the supernatant of KYSE-450/PBMC coculture system after metformin treatment. Both of which are indicators of T cell activation. T cell mediated tumor killing assay showed that metformin inducing PD-L1 downregulation could protect T cell function, and it could be reversed by IL-6. It showed that metformin enhanced its efficacy in TE-7 cells-harboring mice in the combination treatment group, reflected by tumor sizes assay, and in vivo imaging system.

Conclusion

Various approaches are under way to expand the benefits and improve the efficacy of these immune checkpoint inhibitors. Another approach is combining immunotherapy with existing anticancer therapies. In this regard, we have evaluated the mechanism of metformin inhibiting PD-L1 expression in ESCC. This finding indicated that metformin significantly improved the antitumor effects by anti-PD-1 blockade without detectable toxicity and suggested that metformin has strong potential to be used in combination with immunotherapy.
166 CLINICAL IMPACT OF NEW BIOMARKERS IN THE PATIENTS WITH ESOPHAGEAL CARCINOMA
Authors: Shimada Hideaki , Yajima Satoshi , Oshima Yoko , Nanami Tatsuki , Ito Masaaki , Suzuki Takashi , Shiratori Fumiaki , Hoshino Isamu , Nabeya Yoshihiro
Published: September 2021

We have developed several new biomarkers in patients with esophageal carcinoma. In this paper, we reviewed the clinical impact of serum autoantibodies, growth factors, blood counts, and other serum tumor markers.

Methods

Blood samples of patients with esophageal carcinoma were obtained before surgery and were stored at −80°C until the ELISA assay. Target tumor antigens for autoantibodies were SURF1, LOC, HOOK2, AGENCOURT, TROP-2, TRIM21, GLUT-1, Myomegalin, Makorin-1, CUEC-23, ECSA-1, p53, and NY-ESO-1. Growth factor-related molecules were followed; midkine, VEGF, PDECGF, and HGF. The other markers were followed; platelet, CRP, IAP, SCC-Ag, CYFRA21-1, and fibrinogen.

Results

A total of 24 biomarkers were evaluated for their clinical impact on patients’ survival and tumor stages. High positive rates, more than 40% were found in SURF1, Myomegalin, midkine, and HGF. Although the majority of autoantibodies did not have a prognostic impact, all the growth factors have a prognostic impact on patients’ survival. Lutine blood tests, such as platelet count, neutrophil-lymphocyte ratio, fibrinogen, and CRP, were also useful to predict prognosis.

Conclusion

We have evaluated the clinical impact of 24 new biomarkers, including 13 autoantibodies, for the patients with esophageal carcinoma. Although the autoantibodies were useful to detect relatively early stage of the disease, the prognostic impact of these biomarkers was limited. All growth factors were useful to predict patients’ survival.
170 SKELETAL MUSCLE LOSS DURING NEOADJUVANT CHEMOTHERAPY IS A PREDICTOR OF MAJOR POSTOPERATIVE COMPLICATIONS IN PATIENTS WITH ESOPHAGUS CANCER
Authors: Higashizono Kazuya , Sato Shinsuke , Nagai Erina , Taki Yusuke , Nishida Masato , Ohata Kou , Kanemoto Hideyuki , Watanabe Masaya , Oba Noriyuki
Published: September 2021

It is known that various factors, including surgical stress, nutritional deficits and sarcopenia, affect the incidence of postoperative complications. The aim of this study is to identify the predictors of major complications (Clavien-Dindo ≥II) after esophageal resection following neoadjuvant chemotherapy (NAC).

Methods

Forty-nine patients with esophageal cancer undergoing NAC and surgery between January 2017 and December 2019 were identified from our surgery database and retrospectively analyzed. Onodera prognostic nutritional index (PNI) was used as the indicator of nutritional status. For the evaluation of skeletal muscle mass, computed tomography imaging of the total cross-sectional muscle tissue measured at the third lumbar level defined the skeletal muscle index (SMI). Images were collected before and after NAC. Univariate and multivariate logistic regression analyses were used to assess the association between various predictors and major postoperative complications.

Results

Of the Forty-nine patients, 20 patients (40.8%) had major complication after surgery. Of the 20 patients, 5 had pneumonia and 4 had anastomotic leakage. Nine patients (18.3%) complete planned dose of NAC. SMI reduction was observed in 42 patients (85.7%) during NAC. According to univariate analysis, SMI reduction during NAC, and PNI before chemotherapy were significantly associated with major postoperative complications (P = 0.032, P = 0.035, respectively). According to multivariate analysis, SMI reduction during NAC is an independent predictor for the incidence of major postoperative complications (P = 0.0034).

Conclusion

Skeletal muscle loss during neoadjuvant chemotherapy can be an useful predictor of major postoperative complications in patients with esophageal cancer.
210 SALVAGE SURGERY AFTER DEFINITIVE CHEMORADIOTHERAPY FOR CT4 THORACIC ESOPHAGEAL CANCER
Authors: Sato Hiroshi , Miyawaki Yutaka , Fujiwara Naoto , Sugita Hirofumi , Sakuramoto Shinichi , Okamoto Kojun , Yamaguchi Shigeki , Koyama Isamu
Published: September 2021

Salvage surgery after curative chemoradiotherapy for cT4 thoracic esophageal cancer is the only treatment that can be expected to cure, but the incidence of postoperative complications is also high, and its indication and timing should be carefully considered. In our hospital, radical chemoradiotherapy was positively performed for cT4 chest esophageal cancer, and salvage surgery was positively performed.

Methods

We examined 24 salvage surgery cases after chemo radiotherapy for cT4 esophageal cancer, which was conducted at our hospital from April 2012 to June 2018. The effect of treatment is determined after radical chemoradiotherapy. In the case of PR/SD, salvage surgery or salvage surgery is performed after additional chemotherapy. Salvage surgery was actively considered when it was considered resectable and resistant. In cases where CR was obtained, salvage surgery was performed in cases where relapse was observed during the course. Invasion organs were 9 cases of aorta, 11 cases of tracheobronchial, and 4 cases of others.

Results

No hospital deaths.Postoperative complications were 50%. Pneumonia 21%, anastomotic leak 13%. The period from the start of radical chemoradiotherapy to salvage surgery was 2.2 to 17.0 months (median 3.8 months). Grade 3 was observed in 4 cases. The 3-year OS was 80%, and the 3-year PFS was 43%. The recurrence rate of cT4b (Ao) was 75%, and that of cT4b (tracheobronchial) was 57%. In addition, the recurrence rate was high in the cases that were cN (+) and all the cases had postoperative recurrence in the cases that were pN (+) in the histopathological examination after salvage surgery.

Conclusion

Since cT4 was down-staged and enabled for radical surgery, dCRT could eventually be a powerful preoperative treatment. There was no death at the hospital, and postoperative complications are considered acceptable.Consideration of multidisciplinary treatment for patients with positive lymph node metastasis is needed. There are not a few cases of pCR, and surgical indications and informed consent are more important.
263 MEDIASTINAL LYMPHADENECTOMY UNDER LAPAROSCOPIC ASSISTED SINGLE-PORT INFLATABLE MEDIASTINOSCOPY THROUGH LEFT NECK APPROACH
Authors: Gan Xiangfeng , Li Xiaojian , Cao Qingdong
Published: September 2021

Minimally invasive esophagectomy (MIE) has developed for decades. However, conventional MIE requires transthoracic operation, it could increase the risk of many perioperative cardiopulmonary complications. Therefore, mediastinoscopy-assisted transhiatal esophagectomy has been proposed, but the traditional surgical methods have shortcomings, such as unclear vision, especially during the dissection of mediastinal lymph nodes. A new approach of mediastinal lymphadenectomy under single-port inflatable mediastinoscopy through one left-neck incision was proposed.

Methods

With pneumomediastinum, esophagectomy was to be performed over the aortic arch to the level of lower edge of the left main bronchus, and the lymphadenectomy of 106recL has also accomplished during this process. At the level of lower edge of the right subclavian artery (RSA), between the trachea and the esophagus, the instruments could get accessed to the right RLN. The lymphadenectomy could get accomplished up to 2-cm at the upper edge of the RSA. Between the trachea and esophagus, the lymphadenectomy of 107 would be performed along the trailing edge of the trachea down to the carina.

Results

56 patients with esophageal squamous cell carcinoma from March to September 2019 who underwent this operation. The mean age of 56 patients was 67.4 years, 46 were males, and 10 were females. Preoperative TNM staging: T1b, 10 cases; T2, 35 cases; and T3, 11 cases. The median number of mediastinal LNs removed was 17 (9 to 23); 6 (2 to 9) along the left RLN; 3 (1 to 6) along the right RLN. 7 patients (12.5%) developed RLN palsy. All of the 7 RLN palsy were left side, none of them appeared at 3-month postoperation.

Conclusion

This single-port inflatable mediastinoscopy technology could remove the upper mediastinal LNs on both sides with a single incision on the left neck, avoid trauma to the right neck. The bilateral RLN could be clearly exposed and protected under the mediastinoscopy. Compared with previous surgical techniques, this surgery is less invasive, and the bilateral RLN is more clearly revealed. The surgical procedure described here is the first mediastinal lymphadenectomy under mediastinoscopy through one single left-neck incision.

Video

https://www.jianguoyun.com/p/DUvIaIsQoPWPBhj1mt8C.
285 RIGHT COMPARED WITH LEFT THORACIC APPROACH ESOPHAGECTOMY FOR PATIENTS WITH MIDDLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Zheng Yan , Xing Wenqun , Li Yin , Liu Xianben , Zhang Ruixiang , Sun Haibo
Published: September 2021

The open surgical approaches for esophageal cancer (EC) can be mainly divided into the right and left transthoracic approach in China. Although it shows an increasing number of right side approach, the optimal surgical technique remains unclear. This study attempt to compare the long-term survival between two approaches in a large cancer center with rich experience of both side transthoracic approach.

Methods

The patients who underwent right transthoracic approach esophagectomy (Right, McKeown) and left transthoracic approach esophagectomy (Left, Sweet or chest neck dual-incision) for esophageal squamous cell carcinoma (ESCC) during January 2015 to January 2018 were included. The overall survival (OS) rate and perioperative data between two groups were retrospectively analysed.

Results

We included 437 patients who underwent Right (n = 202) or Left (n = 235) approach for ESCC. There was a significantly longer median operative time (250 min vs. 190 min, P < 0.001) and longer median postoperative hospital stady days (17 days vs. 14 days, P < 0.001) in Right groups. The OS at 34-months was 69.83% and 67.32% in Right and Left groups, respectively; hazard ratio (HR) (95% CI): 1.121 (0.723–1.737), p = 0.611.

Conclusion

For middle thoracic ESCC without suspected lymph node metastasis in the upper mediastinum, the esophagectomy through left thoracic approach could achieve the same OS with right side, and better short-term outcomes.
308 PROGNOSTIC FACTORS OF PATIENTS WITH LYMPH NODE RECURRENCE AFTER ESOHAGECTOMY
Authors: Tanaka Koji
Published: September 2021

Background: Lymph node recurrence (LNrec) is a frequent form of recurrence in esophageal squamous cell carcinoma (ESCC), but is often characterized as a systemic disease. However, loco-regional treatment may provide cure for lymph node-only recurrence without distant metastases. There is no consensus on the outcome of multidisciplinary treatment, including surgical resection. The aim of this study is to identify the prognostic factors and to establish treatment strategy for LNrec.

Methods

Methods: Among 1160 patients who underwent esophagectomy for ESCC between 2004 and 2017 in our hospital, 117 patients (12.4%) who had LN-only recurrence without distant recurrence were analyzed retrospectively. The standard operation consisted of subtotal esophagectomy with 2- or 3-field lymph node dissection via right thoracotomy or video assisted thoracic surgery (VATS) and gastric tube reconstruction. Recurrence site, treatment for LN rec, and survival after recurrence were examined. Survival curves were plotted using the Kaplan–Meier method, and differences between survival curves were compared using the log-rank Test.

Results

The 3-year survival rate after recurrence of all lymph node-only cases was 19.5%. The 3-year survival rate after recurrence was significantly better in patients with single recurrence: 25.1%/multiple recurrence 12.4% (p = 0.0222). The 3-year survival rate after recurrence was initial p-stage: II or lower/III or higher = 39.0/14.1% (p = 0.0107). Patients with a high p-stage at initial surgery had a significantly poor prognosis. Patients who underwent local treatment (C RT or surgery) after recurrence had significantly better prognosis than those who did not (25.8/10.6%; p = 0.0006).

Conclusion

Single LN rec, low initial p-stage, local treatment (CRT or surgery) were identified as prognostic factors in patients with LN-only recurrence.
369 POOR CORRELATION BETWEEN FDG-PET AND PATHOLOGIC RESULTS AFTER EXPERIMENTAL NEOADJUVANT IMMUNOCHEMOTHERAPY FOR GASTROESOPHAGEAL ADENOCARCINOMA: RESULTS OF A CLINICAL TRIAL
Authors: Alcindor Thierry , Opu Touhid , Mueller Carmen , Ah-Son Nicolas , Hickeson Marc , Marcus Victoria , Camilleri-Broet Sophie , Fiset Pierre-Olivier , Ferri Lorenzo
Published: September 2021

A lack of FDG-PET response to neoadjuvant chemotherapy for gastroesophageal adenocarcinoma is considered as indicative of a poor prognosis, whereas pathologic complete or near-complete response (pCR/near-pCR) predicts a more favorable outcome. In a single-arm phase II trial of perioperative immunochemotherapy, we sought to establish a correlation between the results of an FDG-PET performed after the neoadjuvant part of the treatment and the pathologic results obtained after surgery.

Methods

Inclusion criteria: locally advanced gastroesophageal adenocarcinoma (T3 and/or N+); adequate organ function; ECOG PS 0–1; no contraindication to immunotherapy; Staging: CT, FDG-PET, EUS, diagnostic laparoscopy. Eligible patients receive docetaxel/cisplatin/5-FU (mDCF) on day 1 and avelumab on day 4 of each 2-week cycle and are restaged after 4 cycles. FDG-PET response is defined as reduction of >35% of pre-treatment SUV. Surgery is performed if no disease progression. Four cycles of mDCF/avelumab are administered after surgery. Tumor regression is scored from 0 (no tumor cells) to 3 (no tumor regression). The primary endpoint is the pCR/near-PCR rate (score 0–1).

Results

As of February 24, 2020, 28 patients have been enrolled and 22 have been operated. Paired FDG-PET response and pathologic response data are available for 21 patients. We observed 16/21 FDG-PET responses and 6/21 pCR/near-pCR. Of the latter, 4 were associated with an FDG-PET response and 2 with no FDG-PET response. Ten patients with score 3 tumor regression had had FDG-PET response. No statistical correlation could be found between FDG-PET response and likelihood of pCR/near-pCR.

Conclusion

Given the discrepancy observed between FDG-PET and pathologic results, the need for a repeat FDG-PET for gastroesophageal adenocarcinoma after neoadjuvant immunochemotherapy and before surgery should be questioned. Analysis of the tumor microenvironment could possibly explain these results. Future studies will look into correlation between the results presented and survival.
436 PRONE THORACOSCOPIC ESOPHAGECTOMY FOR PATIENTS WITH LOW PULMONARY FUNCTION
Authors: Takiguchi Gosuke , Oshikiri Taro , Horikawa Manabu , Kitamura Yu , Horie Kazumasa , Urakawa Naoki , Hasegawa Hiroshi , Yamamoto Masashi , Shingo Kanaji , Matsuda Yoshiko , Yamashita Kimihiro , Matsuda Takeru , Nakamura Tetsu , Suzuki Satoshi , Kakeji Yoshihiro
Published: September 2021

Thoracoscopic esophagectomy in the prone position (TEP) for esophageal cancer is reported to have superiority in preserving postoperative respiratory function and reducing postoperative respiratory complications. In Japan, the majority of patients with esophageal cancer are smokers and have obstructive ventilation disorders. But, the feasibirity and safety of TEP for patients with low respiratory function is unclear.

Objectives

To clarify the feasibirity and safety of TEP for esophageal cancer patients with obstructive respiratory function.

Methods

The 95 patients with obstructive respiratory disorder who underwent TEP and gastric tube reconstruction via posterior mediastinal route for esophageal cancer from January 2016 to April 2019 were divided into the two groups, low respiratory function (LRF) group and the control group. Short-term outcomes were compared between two groups.

Results

The control group was 73 cases, and the LRF group was 22 cases. Propensity score matching using age, gender, cT, and cN as covariates was used to identify matched patients (22 per group) in both groups. There were no differences in operation time of overall and intrathoracic part, or blood loss in each group. In the postoperative complications, pneumonia (13.6% vs. 9.1%), recurrent laryngeal palsy (18.2% vs. 22.7%), anastomotic leakage (13.6% vs. 13.6%) and hospital stay (36.3 days vs 27.5 days) were no differences in both groups.

Conclusion

TEP can be feasible and safe for the patients with obstructive ventilation disorder and low respiratory function.
493 THE IMPACT OF PARATRACHEAL LYMPHADENECTOMY ON SURVIVAL AFTER ESOPHAGECTOMY: A NATION-WIDE PROPENSITY SCORE MATCHED ANALYSIS
Authors: Hagens Eliza , Kingma B , Berge Henegouwen M , Borggreve A , Ruurda J , Hillegersberg R , Gisbertz S
Published: September 2021

Lymph node status in patients with esophageal carcinoma is one of the most important prognostic parameters in esophageal carcinoma. The distribution pattern of lymph node metastases and the optimal extent of lymphadenectomy remains unclear. Therefore the extent of high mediastinal lymphadenectomy, including removal of the paratracheal lymph node stations, in esophageal surgery is a subject of debate. The aim of this study is to investigate the impact of paratracheal lymphadenectomy on survival.

Methods

For this nation-wide population-based cohort study, patients with an esophageal or gastro-esophageal junction carcinoma treated by elective transthoracic esophagectomy with two-field lymphadenectomy between 2011 and 2017 were included from the national Dutch Upper Gastro-intestinal Cancer Audit (DUCA) registry. Patients who died within 30 days after surgery or where lymphadenectomy data was missing were excluded from analyses. After propensity score matching patients with adenocarcinoma and squamous cell separately, overall survival was compared between patients who underwent paratracheal lymphadenectomy versus patients who did not. Subgroup analysis was performed in patients with cN0 disease.

Results

3143 patients were included in the DUCA. A total of 512 patients with adenocarcinoma (n = 256 vs. n = 256) and 157 patients with squamous cell carcinoma (n = 62 vs. n = 62) were matched. For both patients with adenocarcinoma and squamous cell carcinoma a paratracheal lymphadenectomy was not significantly associated with longer overall survival (11 versus 10 months, p = 0.209 and 12 versus 11 months, p = 0.206, figure 1). In subgroup analysis, including patients with a squamous cell carcinoma and cN0 disease, paratracheal lymphadenectomy was associated with longer survival (13 versus 9 months, p = 0.011). This was not seen in patients with adenocarcinoma (11 versus 9 months p = 0.263).

Conclusion

In both patients with an esophageal adenocarcinoma as squamous cell carcinoma, the addition of paratracheal lymphadenectomy during transthoracic esophagectomy was not significantly associated with longer survival. However, a significantly longer survival was seen in cN0 patients who underwent an additional paratracheal lymphadenectomy, therefore routine removal of paratracheal lymph nodes might still be beneficial. Further studies are warranted with larger subgroups to investigate the impact of an additional (routine) paratracheal lymphadenectomy on survival.
54 CLINICOPATHOLOGICAL FEATURES AND TREATMENT OUTCOMES OF ESOPHAGOGASTRIC JUNCTIONAL CARCINOMA TREATED WITH CURATIVE SURGERY
Authors: Kaida Sachiko
Published: September 2021

Compared to Western countries, Japanese esophagogastric junctional carcinoma (JC) demonstrates different epidemiologic backgrounds; squamous cell carcinoma is dominant over Barrett adenocarcinoma, and there is no consensus on surgical approach or dissection range of lymph node. JC is defined as the cancer, that is the center of the tumor is within 2 cm from the esophagogastric junction to the esophagus and stomach respectively by the Japanese Classification of Esophageal Cancer, 11th edition.

Methods

According to the definition, we examined the clinicopathological features and treatment outcomes of patients who underwent curative resection and pathologically defined as JC. From 2012 to 2019, 23 consecutive patients with JC who received with curative surgery in Shiga University of Medical Science Hospital were included. Clinicopathological classification was based on Japanese Classification of Esophageal Cancer, 11th edition. The patients consisted of 18 males and 5 females, median age was 68 (43–91) years old.

Results

Pathological diagnoses were 19 adenocarcinoma, 1 squamous cell carcinoma, 2 mixed adenoneuroendocrine carcinoma (MANEC) and 1 malignant melanoma. Patients with Barrett’s esophagus were 7 cases (30.4%). Surgical procedure was esophagectomy via right thoracotomy 9 cases, esophagectomy via left thoracotomy 2 case and laparotomy 12 cases. Tumor invasion was pT1:6 (26.1%), pT2:3 (13.0%), pT3:5 (21.7%) and pT4:9 (39.1%). Lymph node metastases were observed in 16 cases (69.6%) and #1,2,3:15 cases (93.8%), #4,5: 3 cases (18.8%), #7,8a,9: 6 cases (37.5%), #19,20: 3 cases (18.8%) and #105–110: 5 cases (31.3%). Among 7 recurrence patients, peritonitis carcinomatosa was 4 cases.

Conclusion

In most positive lymph node metastasis cases, metastasis was observed in #1, 2 and 3 lymph nodes, but metastasis to the cervical lymph node was not observed. In the G, GE cases, right thoracotomy was not performed because there were no metastases to the upper mediastinal lymph nodes. These results suggested that surgical operation could be reduced to proximal gastrectomy for early G, GE cases. Future studies are necessary to further evaluate this result.
548 COMPARISON OF ESOPHAGECTOMY OUTCOMES BETWEEN A NATIONAL CENTER, A NATIONAL AUDIT COLLABORATIVE, AND AN INTERNATIONAL DATABASE USING ECCG STANDARDIZED DEFINITIONS
Authors: Reynolds John V , Elliott Jessie A , Donlon Noel , Donohoe Claire , Ravi Narayanasamy , Kuppusamy Madhan Kumar , Low Donald E
Published: September 2021

The ECCG developed a standardized platform for reporting operative complications, with consensus definitions, and DUCA adopted these definitions and have reported a comparison against these benchmarks. The aim of this study was to report five year complications data using the standardized definitions of the Esophageal Complications Consensus Group (ECCG), and to compare with published ECCG benchmark studies from the collaborative group and from the Dutch Upper Gastrointestinal Cancer Audit (DUCA).

Methods

All patients undergoing multimodal therapy or surgery with curative intent from 2014 to 2018 inclusive were studied. All data were recorded prospectively and maintained internally as well as entered onto a secure online database (Esodata.org) from 2015. Statistical analysis was performed using SPSS® (version 18.0).

Results

219 patients (mean age 67; 77% male) underwent open resection, 66.6% via transthoracic en bloc resection. 30-day and 90-day mortality were 0.0 and 0.9%, respectively. The anastomotic leak rate was 5.4%, and chyle leak 5.4%. Pneumonia was recorded in 18.2%, respiratory failure 10.9%, and ARDS in 2.7%. Atrial dysrhythmia occurred in 22.8%, recurrent nerve injury 3.1%, and delirium in 5.0%. Compared with both ECCG and DUCA, where MIE constituted 47% and 86% of surgical approaches, respectively, overall complications were similar in this open series, as was complications severity, however anastomotic leak rate were several-fold less, and mortality rates were lower.

Conclusion

In this unselected consecutive series and comparative audit with benchmark averages from the ECCG and DUCA publication, a low mortality and anastomotic leak rate were the key differential findings. Although not risk-stratified or directly matched, the severity of complications from this ‘open’ series is consistent with series containing large numbers of total or hybrid MIE, highlighting a need to adhere to these strictly defined definitions in further prospective research and randomized studies.
661 EFFICACY OF ROBOT ASSISTED MINIMALLY INVASIVE ESOPHAGECTOMY: PROPENSITY MATCHED ANALYSIS OF RAMIE IN COMPARISON WITH CONVENTIONAL MIE
Authors: Fujita Takeo , Sato Kazuma , Ozaki Asako , Akutsu Tomohiro , Fujiwara Hisashi , Daiko Hiroyuki
Published: September 2021

Robot assisted minimally invasive esophagectomy (RAMIE) has been reported to be potential advantages in previous reports. Here we demonstrate the difference between these two minimally invasive procedures and investigated the surgical results of RAMIE in comparison with MIE using propensity matched-cohort.

Methods

We investigated 154 cases of thoracic esophagectomy conducted between 2020/1 to 2021/1. Among these cases, we analyzed 30 cases of RAMIE in comparison with 30 cases of matched-cohort which conducted conventional thoracoscopic esophagectomy (MIE) in the prone. Then we evaluated the surgical results between two groups.

Results

There were no differences in age (69.2 vs 69.1 yo), gender (M:F = 24:6 vs 24:6), cStage (Stage I,II,III,IV:6,3,14,7 vs 8,3,14,5), and preoperative chemotherapy (70% vs 66.7%) between RAMIE and matched-cohort MIE. There was statistically significant difference in total time of thoracic phase (233.1 vs 173.3 min; p < 0.01). There were no significant differences in postoperative events in RAMIE vs MIE (Clavien-Dindo Grade 1≧; Recurrent laryngeal nerve paralysis (RLNP) (16.7 vs 20.0%; p = 0.19). However, after the learning curve archived, seldom cases were diagnosed postoperative RLNP in RAMIE cases in comparison with MIE (p = 0.06).

Conclusion

We demonstrated the formalization of our procedure and surgical results of RAMIE. There were no significant differences in postoperative events between two groups. However RLNP was lower after the learning peak. Incidence of RLNP could be reduced in RAMIE.
662 MICROVASCULAR MYOCUTANEOUS AND CUTANEOUS FREE FLAP RECONSTRUCTION FOR PATIENTS WITH TERMINAL ESOPHAGOSTOMY AFTER COMPLICATED ONCOLOGICAL ESOPHAGUS RESECTION
Authors: Pölsler Lukas , Presl Jaroslav , Brandtner Christian , Gaggl Alexander , Hutter Jörg , Koch Oliver , Emmanuel Klaus
Published: September 2021

Persisting anastomotic leak after oncological esophagectomy is a severe problem associated with high mortality and morbidity. Unfortunately, treatment options with promising results are scarce especially when conventional operative and endoscopic methods have failed. Due to limitation of oral intake and need for artificial nutrition quality of life is reduced. Microvascular myocutaneous and cutaneous free flap (MFF) reconstruction could be a promising alternative.

Methods

This retrospective cohort study presents seven patients treated between March 2017 and November 2020 at our surgical department, with terminal esophagostomy after complicated oncological esophagus resection without further feasible treatment options. All Patients received anastomotic MFF reconstruction. We have examined postoperative outcomes, complications according to Clavien-Dindo-Classification and patient contentment with a questionnaire. Additionally, we described important procedure related facts.

Results

The included seven male patients had median age of 65.15 years (range: 48–75). MFF function was adequate in six out of seven patients, graft rejection appeared in one patient. Five patients initially had good results, surgical revision was performed in one patient to ensure graft function. Postoperative complications appeared in 6/7 patients (Table 1). Mean duration of inpatient care was 63 days (Range: 24–156). At time of evaluation, one patient has died cancer related. No more additional nutrition was needed in 3/6 patients with adequate graft function. The majority of patients reported an improved quality of life compared to preoperatively.

Conclusion

MFF free flap can be a safe and feasible treatment option for patients with terminal esophagostomy after complicated oncological esophagus resection without further treatment options or in patients with complicated postoperative course with complex combined defects. The renewed ability of oral food intake results in a significant improvement of quality of life for the patients. No procedure related mortality was observed. Number of patients with regained ability of oral intake is encouraging.
663 QUANTITATIVE PERFUSION ASSESSMENT TO PREDICT ANASTOMOTIC LEAK AFTER ESOPHAGECTOMY
Authors: Ishikawa Yoshitaka , Breuler Christopher , Chang Andrew C , Lin Jules , Orringer Mark B , Lynch William R , Lagisetty Kiran H , Wakeam Elliot , Reddy Rishindra M
Published: September 2021

Impaired gastric conduit perfusion is a risk factor for anastomotic leak after esophagectomy. Most studies evaluating conduit perfusion have been qualitative with limited impact on post-operative care. The aim of this study is to evaluate the feasibility of intraoperative quantitative assessment of gastric conduit perfusion with indocyanine green (ICG) fluorescence angiography as a predictor for cervical esophagogastric anastomotic (CEGA) leak after esophagectomy.

Methods

ICG fluorescence angiography using the SPY elite® (Stryker, MI, USA) system was performed in patients who had undergone a transhiatal or McKeown esophagectomy CEGA from July 2015 through December 2020. Fluorescence angiography assessed Ingress (dye uptake) and Egress (dye exit). Ingress Index, Ingress Time, Egress Index, and Egress Time at two anatomic landmarks (tip of the conduit, and 5 cm from tip) were calculated from the measured curve of fluorescence (Figure). The collected data between the leak (L) group and the no-leak (NL) group were compared by both univariate and multivariable analyses to analyze risk factors potentially associated with CEGA leak.

Results

304 patients were evaluated. There was no significant difference in patients' demographic and post-operative complications between the groups (L n = 73; NL n = 231), except for anastomotic stricture (42.5 vs 9.1%, p < 0.01). 5 cm and Tip Ingress Index were significantly lower in L (35.0 vs 45.1% and 17.4 vs 25.7%, p < 0.01). 5 cm Ingress Time was significantly higher in L (70.6 vs 56.8 sec, p < 0.01). On multivariable analysis, these variables retained statistical significance, suggesting that these three variables can be used to predict future leak.

Conclusion

This study revealed that gastric conduit perfusion correlates with the incidence of CEGA leak. Intraoperative measurement of gastric conduit perfusion may be predictive for CEGA leak following esophagectomy. These variables can be easily collected intraoperatively with the SPY study and used to make clinical decisions which may avert CEGA leak.