bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.001) and longer median postoperative hospital stady days (17 days vs. 14 days, P &lt; 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

Abstract

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

Abstract

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 &gt;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

Abstract

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.