bluuebunny/crossref_metadata_2025_split huggingface dataset:
Esophageal cancer: Five years of experience in an oncological reference center.
Authors: Cessa-Zanatta José Carlos , Alcorta-Nuñez Fernando , Salazar-Mejía Carlos Eduardo , Muñoz-Ayala Juan Manuel , Gonzalez-Alcorta Celia Beatriz , Hernandez Barajas David , Gonzalez-Guerrero Juan Francisco , Vidal-Gutiérrez Oscar , Alcorta-Garza Adelina 
Published: May 2019

e15536 Background: Squamous cell carcinoma and adenocarcinoma represent approximately 95% of malignant tumors of the esophagus. For most cases of the 20th century, squamous cell carcinoma was the predominant lineage. In the 1960s, squamous cell carcinoma accounted for more than 90% of all esophageal tumors in the United States of America, and adenocarcinoma was considered so uncommon that some oncological associations questioned its existence. However over time the incidence of esophageal adenocarcinoma (predominantly in the distal esophagus and gastroesophageal junction) has increased dramatically in Western countries, with adenocarcinoma now causing more than 60% of all esophageal cancers in the United States of America, unlike the rest of the world, where squamous cell carcinoma continues to predominate. Squamous cell carcinoma and adenocarcinoma differ in a significant number of clinical features, including tumor location and predisposing factors. Smoking and alcoholism are major risk factors for the development of squamous cell carcinoma, while the Barrett's esophagus with intestinal metaplasia (a complication of gastroesophageal reflux disease), obesity, and smoking are the risk factors related to adenocarcinoma of the esophagus. Objectives: To determine the incidence of esophageal adenocarcinoma in Mexico and its main characteristics, such as epidemiology, histological type and main risk factors. Methods: A descriptive analysis was conducted in which the histological type, age of diagnosis, location, age of the patients and risk factors were compared. Results: Average age on the studied population was 67.4 years (minimum 37, maximum 91); 74.3% of the subjects were male and 20.4%, female. It was found that the predominant histological type was Adenocarcinoma in 40.7% against 28.3% of the Epidermoid. Average age of diagnosis was at 65.88 years (minimum 37, maximum 89). In frequency of localization, lower third in 22.1%, union GE in 20.4%, middle third in 15%, and upper third in 12.4%). The predominant risk factors in our study were smoking (31%), alcoholism (36.3%) and GERD (12.4%). Conclusions: Oesophageal adenocarcinoma continues to be the most prevalent presentation of esophageal cancer in our population, despite epidemiological changes over time.
Postoperative adjuvant chemotherapy for thoracic pathological T3N0M0 esophageal cancer: A propensity score-matched analysis (APEC Study 1).
Authors: Wang Qifeng , Li Tao , Han Yongtao , Li Qiang , Peng Lin , Xie Tianpeng , Fang Qiang , Yang Xiaojun , Zhuang Xiang , Dai Wei , Jiang Yingchun , Wang Yi , Lv Jiahua , Wu Lei , Cao Bangrong , Lan Mei , Lang Jinyi 
Published: May 2019

e15537 Background: The role of postoperative chemotherapy (POCT) in thoracic esophageal squamous cell carcinoma (TESCC) has not been addressed . The aim of this study was to investigate whether POCT after an R0 resection improves outcomes in pT3N0M0 TESCC compared with operation alone. Methods: This study included 604 patients with pT3N0M0 TESCC who were treated at Sichuan Cancer Hospital from January 2009 to December 2017. The patients were divided into two groups: a surgery plus postoperative chemotherapy group (PORT group) comprising Surgery alone patients who underwent after an R0 resection and a surgery group (S group). Propensity score matching was used to create patient groups that were balanced across several covariates (n= 246 in each group). Outcome measures included overall survival (OS), disease free survival (DFS). Results: In the whole group 5-year OS and PFS were 58.4% and 56.0%. In the overall study cohort, 5-year OS (68.3% versus 50.4%, p < 0.0001) and DFS (65.5% versus 45.8%, p < 0.0001) rates were significantly higher in the POCT group than in the S group. These data were confirmed in the matched samples (5-year OS, 68.3% versus 49.5% [p < 0.0001]; DFS, 65.5% versus 42.5% [p < 0.0001]). Multivariate Cox analyses in the matched samples revealed that surgery and postoperative POCT were independently associated with longer OS (hazard ratio = 0.553, 95% confidence interval: 0.391–0.726, p < 0.0001) and longer DFS (hazard ratio = 0.556, 95% confidence interval: 0.416–0.744, p < 0.0001) than resection alone. Subgroup analysis found : POCT with IIA in pT3N0M0 have not longer OS and DFS ( p = 0.122 and p = 0.193). POCT with IIB in pT3N0M0 have the longer OS and DFS(p < 0.0001 both). Conclusions: Postoperative adjuvant Chemotherapy is strongly associated with improved OS and DFS in patients with pT3N0M0 TESCC. A multicenter, randomized phase III clinical trial is warranted to confirm these findings.
Not all HLA loss facilitate immune escape.
Authors: Zhang Li , Peng Ping , Zhao Yongtian , Zhao Zhikun , Chen Yuan 
Published: May 2019

e15540 Background: Evolution of tumor immunogenicity during immune checkpoint blockade therapy affects tumor response. This study is to investigate the potential mechanisms of the evolution by identifying the differences in immunogenetics between primary tumor and various metastaticlesions after immunotherapy. Methods: This study was approved by IRB. Three types of tissues from a patient with advanced squamous esophageal cancer were obtained three months after anti-PD-1 therapy. The primary tumor (E) was obtained from surgery, the metastatic tumor tissues were obtained from biopsy of the testicular (T)and skin (S) lesions. The presence of immune cell infiltrates and the availability of target antigens defined by mutated neoantigens in these 3 different tissues were examined. The genetic changes from these lesions were analyzed by whole-exome sequencing and RNA sequencing.The inter-lesional immunogenetic heterogeneity between responsive and non-responsive tumor lesions is interpreted. Results: The patient was evaluated at 1 and 3 months after anti-PD-1 therapy with image examinations. The skin metastatic lesion showed significantly decrease in size, but the testicular metastatic lesion failed to respond to the therapy. To correlate tumor response with immunogenetic heterogeneity, 3 specific genotypic changes were examined and compared. 1. Phylogenetic analysis of multi-site mutational profiles showed that metastases were more closely related to each other than to the primary tumor. Truncal and shared mutations were generally clonal with high cellular prevalence, whereas private mutations had medium to low cellular prevalence indicating subclonal status. 2. Although human leukocyte antigen (HLA) loss occurred in S, the numbers of high expression mutation that can be recognized and presented by HLA were the highest. Compared to E,S and T, an overall higher expression of HLA genes was observed in the S. 3. The number and state of different kinds of immune cell were evaluated. The analysesrevealed an increase in distinct immune cell subsets and activation of specific transcriptional networks that were more pronounced in S than T.s and activation of specific transcriptional networks that were more pronounced in S than T. Conclusions: Recent work has shown that HLA-LOH may result in reduced antigen presentation and thus facilitate immune evasion. This study analysis of inter-lesional heterogeneity during anti-PD-1 therapy demonstrated differential clonal evolution within tumors and potential impact of HLA-LOH on neoantigen presentation and expression.
Immune biomarker expression in the tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma was explored.
Authors: Li Pengfei , Luo Hongli , Chen Yanhui , Wang Yating , Chen Huan , Wu Lihong , Ma Yegang , Zhang Henghui 
Published: May 2019

e15542 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies in China, of which the standard treatment of advanced esophageal cancer is chemotherapy followed by surgery. Recently, immunotherapy has shown great potential in ESCC treatment. The aim of this study was to explore the landscape of immune-related gene expression in the tumor microenvironment (TIME) and further explore the relationship between immune biomarkers and therapeutic effect. Methods: We retrospectively analyzed PDL1(clone sp142)/PD1 expression in a cohort of Chinese patients (male = 92, female = 18; median age = 64, range from 36 to 84) with ESCC. Patient samples were detected in Genecast. Co. from February 2017 to November 2018. Another 6 patients (male = 4, female = 2) who accepted anti-PD1/PD-L1 antibody treatment were analyzed. PD-L1/PD-1 expression and the incidence of CD8, CD57, CD68, CD163 TILs were immunohistochemically. Results: In tumor cells, more than 32% (36/110) samples of ESCC patients was stained with PDL1 (≥1%), while52.8% (21/36) of these patients highly expressed PDL1 (≥10%, 10%-98%). In tumor infiltrating lymphocytes (TILs), 31.82% (35/110) patients expressed PDL1 (≥1%) and 1.82% (2/110) highly expressed PDL1 (≥10%, 10%-50%). For PD1 expression in TILs, 17.27% (19/110) samples were positively stained with PD1 antibody (≥1%). In a subset of ESCC patients who received immune checkpoint blockade therapy (including 2 responders and 4 non-responders), the median percentage of CD163, CD68, PDL1, CD8, PD1 and CD57 were 1.49% (0.44%-9.98%), 0.40% (0.16%-19.08%), 3.74% (0%-45%), 9.52% (4.20%-13.79%), 4.51% (1.37%-33.43%) and 0.68% (0.08%-1.74%), respectively in tumor area and 4.14% (1.85%-15.99%), 1.62% (0.21%-11.47%), 4.87% (0.33%-18.97%), 7.74% (5.88%-14.35%), 3.93% (1.92%-20.54%) and 0.92% (0.27%-2.18%), respectively in stroma area. When compared with non-responders, samples from the responders showed higher CD8 expression in tumor area. Conclusions: Percentage of PDL1/PD1 expression is relatively high in Chinese patients with ESCC. High levels of CD8 positive TILs might be beneficial to patients with ESCC. Clinical investigations with large sample sizes are warranted to prove our findings.
Molecular mechanism of chemoresistance and restoration in human gastric cancer cells.
Authors: Chang Hye Jung , Choi Moon Young , Cho Min-Hee , Lee Kyoung Eun , Lee Soon-Nam 
Published: May 2019

e15544 Background: Gastric cancer is characterized by a high rate of relapse and failure of chemotherapy because of the emergence of drug resistant cells. Hence, resistance to chemotherapy is a major obstacle for the management of gastric cancer. It might be related with the development of cancer stem cells (CSCs). The aim of this study is to investigate the characteristics of the 5-fluorouracil (FU) resistant gastric cancer and to study how to restore the chemosensitivity. Methods: We used the AGS gastric cancer cell line (AGS) and transformed it into a 5-FU resistant cell line (AGS-R). AGS-R was established by continuous exposure of the cells to progressively increasing concentrations of 5-FU for about 1 year and modulating mRNA expression levels of four genes associated with thymidylate synthase (TS). The research methods used were MTT assay, flow cytometry analysis, luciferase reporter assay, western blotting, and siRNA transfection. Results: 5-FU-resistant gastric cancer cell, AGS-R was established by continuous exposure to 5-FU with gradual increase of its concentration for about 1 year. Comparing with AGS, thymidylate synthase (TS) expression in AGS-R was highly increase at transcriptional and translational level. And decreased transcriptional activity of β-catenin in AGS-R was confirmed by Western blotting and luciferase assay. Even though treatment with ICG-001, an inhibitor of β-catenin, showed growth inhibition of AGS in a dose- and time-dependent manner, but it could not in AGS-R. The expression of CD44, well-known CSCs marker, was significantly higher on AGS-R compared to AGS. And the Notch pathway was remarkably up-regulated. Flow cytometry analysis revealed that CD44 expression was reduced on AGS-R transfected with specific siRNA for notch intracellular domain (NICD). Conclusions: This study suggests that chemoresistance of gastric cancer against continuous exposure to 5-FU is associated with decrease of β-catenin activity and development of stemness via the activation of Notch pathway. Therefore, the inhibition of Notch pathway might be a potential therapeutic target in 5-FU-resistant gastric cancer.
Comparison of D2 and D2 plus radical surgery for advanced distal gastric cancer: A randomized controlled study.
Authors: Yu Pengfei , Du Yian , Xu Zhiyuan , Huang Ling , Cheng Xiangdong 
Published: May 2019

e15546 Background: The optimal extent of lymph node (LN) dissection for advanced distal gastric cancer remains controversial. The present study compared the safety and efficacy of extended LN dissection (D2 plus) with standard D2 radical surgery for advanced distal gastric cancer. Methods: Eligible patients were enrolled and randomly assigned into two groups: D2 group and D2 plus group. Patients in the D2 group received standard D2 LN dissection, while patients in the D2 plus group received an additional no. 8p, 12b, 13 and 14v LNs dissection. The clinicopathological and surgical data of these two groups was compared and the factors that may influence survival were analyzed. Results: 70 patients were enrolled, out of which 64 patients were analyzed. There were no significant differences in the operative time, blood loss and complications between the two groups. In the D2 plus group, the positive rate of the no. 12b, 13 and 14v LN was 3.1%, 9.4% and 12.5%, respectively. The positive rate of the no. 13 LN correlated with the duodenal involvement, while the positive rate of the no. 14v LN correlated with no. 6 LN metastasis. The survival analysis indicated that among patients with duodenum involvement, the 3-year disease free survival rate of the D2 plus group was significantly better than that of the D2 group. Conclusions: Duodenum involvement and positive no. 6 LN were high risk factors of advanced distal gastric cancer. D2 plus radical surgery turned out to be safe and feasible, and may improve the prognosis of these patients. However, further clinical trials are still warranted. Clinical trial information: #NCT01836991.
Factors predicting poor survival in early gastric cancer: A SEER analysis.
Authors: Alnimer Yanal Mufeed , Qasrawi Ayman , Katato Khalil 
Published: May 2019

e15548 Background: The benefit of adjuvant treatment in gastric adenocarcinoma patients with muscularis propria involvement but not beyond is unclear. We aim to establish a model that identifies the factors that could adversely affect the prognosis in these patients, whom could potentially benefit from adjuvant treatment. Methods: We used the Surveillance, Epidemiology, and End Results Program (SEER) database to identify subjects with stage T2aN0M0 gastric adenocarcinoma according to the 6th AJCC TNM staging system who underwent tumor resection between 2004-2015. The effect of the following factors on the 5-year overall survival (OS) was evaluated using Kaplan-Meier analysis: demographics, tumor size, grade and site, number of lymph nodes (LNs) being examined and extent of surgery. Factors with a P value < 0.1% in log-rank test were entered in a Cox proportional hazard ratio (HR) model. Results: We identified 1337 patients who met the inclusion criteria. After a median follow-up of 42 months (1-60), the 5-year OS was 64% with the median being unreached. The following factors were significantly associated with shorter OS in univariate analysis: Age > 60 years with a HR = 1.86 (95% CI 1.49-2.32), Non-Hispanics excluding non-Hispanic Asian and Pacific Islanders with a HR = 1.87 (95% CI 1.54-2.28), patients with less than 15 lymph nodes examined at the time of surgery with a HR = 1.86 (95% CI 1.52-2.26), tumors at the fundus and cardia of the stomach compared to other sites with a HR = 1.73 (95% CI 1.37-2.15), those who underwent endoscopic resection with a HR = 2.27 (95% CI 1.16-4.4) and those who didn’t receive chemotherapy with a HR = 1.23 (95%CI 1.001-1.52) . On multivariate analysis; the following factors were predictors for worse OS; Age > 60 years with a HR = 1.97 (95% CI 1.46-2.65), Non-Hispanics excluding non-Hispanic Asian and Pacific Islanders with a HR = 1.45 (95%CI 1.10-2.00), those in whom less < 15 LNs were examined at the time of surgery with a HR = 1.75 (95% 1.38-2.22) and gastric adenocarcinoma at the cardia and fundus with a HR = 1.50 (95%CI 1.20-1.86). Conclusions: Patients with T2aN0M0 gastric adenocarcinoma, and one of the adverse prognostic factors in our Cox-proportional hazard ratio model need to be studied for possible benefit of adjuvant treatment.
Association of high copy number instability (CNI) score with prognosis in patients with gastric cancer after surgical resection.
Authors: Zhang Yanling , Ren Dandan , Mao Beibei , Song Xue , Yang Wanning , Zhang Henghui , Cai Lisheng 
Published: May 2019

e15552 Background: As the fifth most common malignancies and the third leading cause of cancer death in the world, gastric cancer (GC) is often diagnosed in locally advanced or metastatic stage and, therefore, has a poor prognosis. Copy number instability (CNI) score, interpreted as the general measure of genomic instability, was reported as a prognosis predictor of some types of cancer, but its role in prognosis of GC patients remains unknown. The aim of the present study was to investigate its prognostic value in patients with GC after surgical resection and adjuvant chemotherapy. Methods: The present study included 120 patients who had received gastrectomy and adjuvant chemotherapy with stage II-IV GC. Follow-up was available for them. DNA was extracted from primary formalin-fixed paraffin-embedded (FFPE) tumor specimens and matched blood samples. Genomic profiles were analyzed by using a designed panel (1408 genes) based on next generation sequencing (NGS). Results: The most frequently mutated genes were TP53 (49%), PIK3CA (8%), RNF43 (6%) ERBB3 (6%) and APC (6%), and the most frequently amplified genes were TRPS1 (41%), COL1A2 (31%), CSMD3 (29%), ZFHX4 (29%), NAV3 (23%). CNI score was negatively correlated with OS, the CNI-high group had markedly shorter OS than CNI-low group ( p= 0.0093). In addition, there were statistically significant differences in OS between different clinical staging ( p= 0.0468). Moreover, the Cox proportional hazard model showed that CNI score was an independent prognosis factor in GC. Conclusions: The current study indicates that CNI score in primary tumor tissue is an independent predictive prognostic biomarker for GC.
Lactate dehydrogenase and baseline markers associated with clinical outcomes of advanced esophageal squamous cell carcinoma patients treated with camrelizumab (SHR-1210), a novel anti-PD-1 antibody.
Authors: Wang Xi , Zhang Bo , Chen Xuelian , Mo Hongnan , Wu Dawei , Lan Bo , Li Qun , Xu Binghe , Huang Jing 
Published: May 2019

e15559 Background: A small proportion of patients with advanced esophageal squamous cell carcinoma (ESCC) could benefit from immune checkpoint inhibitors, and reliable peripheral blood biomarkers for outcomes of anti-PD-1 immunotherapy were not identified in ESCC. Methods: A total of 43 patients were retrospectively reviewed in the ESCC cohort of a phase I trial from our center. All patients received intravenous camrelizumab (SHR-1210), a novel anti-PD-1 antibody, at a dose of 60 mg, 200 mg or 400 mg (4-week interval after first dose followed by a 2-week schedule) and repeated every two weeks until disease progression or intolerable toxicity. The associations between lactate dehydrogenase (LDH) as well as other peripheral blood biomarkers at baseline and the efficacy of camrelizumab were also investigated. Results: With a median follow-up of 19.6 months, the overall response rate was 25.6% (11/43), including one complete response. Median progression-free survival (PFS) and overall survival were 2.0 months (95% CI: 0-4.1 months) and 8.0 months (95% CI: 7.2-8.8 months), respectively. Notably, four patients achieved a PFS exceeding 12 months, including three patients with a long-lasting duration of response over 1 year. Patients with an elevated baseline lactate dehydrogenase had lower tumor response rates (8.3% vs. 32.3%, p = 0.02) as well as shorter PFS (median: 1.8 vs. 4.0 months; HR 0.39, p = 0.002) and overall survival (median: 4.2 vs. 10.4 months; HR 0.22, p < 0.0001) compared with patients with normal levels. An increase of lactate dehydrogenase level during treatment was significantly associated with disease progression (p = 0.014). Multivariate Cox analysis identified LDH (HR = 0.18), C-reactive protein (HR = 0.27), number of involved organs (HR = 0.31), absolute monocyte count (HR = 0.33) and Eastern Cooperative Oncology Group performance status (HR = 0.36) as independent prognostic factors. Conclusions: Serum LDH, as is readily available in routine clinical practice, is a potential marker for response and a powerful independent factor for survival in advanced ESCC patients receiving anti-PD-1 treatment.
The mutational profile analysis of different response to neoadjuvant chemoradiation therapy in local advanced esophageal squamous cell cancer patients.
Authors: Wang Xiaofeng , Shi Xinying , Yang Xu , Wang Wenqing , Deng Lei , Zhao Lili , Yang Wanning , Mao Beibei , Zhang Henghui , Liang Jun 
Published: May 2019

e15560 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant diseases in the world and especially in China. The combined modality therapy neoadjuvant chemoradiation therapy (nCRT) has become the new standard of care. This study was aimed to investigate the molecular features in cell-free DNA (cfDNA) that is related with the response to nCRT in the local advanced ESCC. Methods: 24 eligible ESCC patients with received nCRT were included and baseline blood were collected from Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. 14 patients had response and the other 10 patients had no response to nCRT, respectively. Both cfDNA fragments and fragmented genomic DNA were extracted for enrichment of a 0.96M size panel covering exon regions of 1,408 genes. Gene alterations were analyzed to explore the relationship between genetic characterizations of cfDNA and response to nCRT. Results: The most common mutated genes were NOTCH1, IRS1, TP53. The somatic alternation of NOTCH1, IRS1, ZFHX4 occurred more frequently in response group than in non-response group. On the contrary, patients with response to nCRT had significantly less mutations of PDE11A, STK11. Moreover, the tumor mutation burden (TMB) of cfDNA in response group was significantly higher than non-response group(p = 0.024). Conclusions: The molecular features in cfDNA of patients with response to nCRT were different from those without response. Five genes’ mutational profile could identify the response and non-response patients with local advanced ESCC. However, prospective studies are needed to validate our findings.