bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic alternate promoter utilization and association with PD-L1 expression in Epstein–Barr virus positive gastric cancer.
Authors: Sundar Raghav , Qamra Aditi , Tan Angie Lay Keng , Zhang Shenli , Ng Cedric Chuan Young , Teh Bin Tean , Lee Jeeyun , Kim Kyoung-Mee , Tan Patrick 
Published: May 2019

e15509 Background: We recently elicited the role of epigenetic promoter alterations as a mechanism of immune-evasion and primary resistance to immune checkpoint inhibition in gastric cancer. High prevalence of epigenetic modifications are known to occur in Epstein-Barr virus associated gastric cancer (EBVaGC). EBVaGC has high response rates to anti-PD-1 immune checkpoint inhibitors and is associated with high levels of PD-L1 expression. However, not all EBVaGC express PD-L1 and mechanisms that mediate these phenomena are unknown. Methods: We performed NanoString profiling and PD-L1 immunohistochemistry (using Dako PD-L1 IHC 22C3) on tissue from gastric cancer patients undergoing primary tumor resections at Samsung Medical Centre, South Korea. NanoString panel was designed for 90 recurrent somatic alternate promoter-related genes, and immune-related genes including PD-L1. EBV status was determined using EBV-encoded RNA in situ hybridization and categorized as EBVaGC and EBV-negative. Samples in the top-quartile of alternate promoter utilization were classified as APhigh and the remaining APlow. Results: A total of 272 samples (EBVaGC n = 79; EBV-negative n = 193) were included in this study. EBVaGC had significantly higher PD-L1 expression (p < 0.001) compared to EBV-negative samples. APhigh group (n = 67) consisted of 61 EBV-negative and 6 EBVaGC samples. EBVaGC APhigh tumors had significantly lower PD-L1 transcript expression compared to EBVaGC APlow tumors (p = 0.011, Wilcoxon-rank sum). Similar correlation was also found with PD-L1 IHC combined positive score (CPS)(median CPS score 1 vs 8, p = 0.047). There was a trend towards poorer survival for EBVaGC APhigh tumors (vs EBVaGC APlow; HR 0.23, 95% CI: 0.046 – 1.23, p = 0.087). EBV-negative APhigh tumors also had lower PD-L1 expression (vs EBV-negative APlow; p = 0.046, Wilcoxon-rank sum). Conclusions: Increased utilization of epigenetic alternate promoter isoforms correlates with lower transcriptomic and protein expression of PD-L1 in EBVaGC. Here we describe a potential mechanism of immune-evasion to explain low immune-infiltration and PD-L1 expression that occurs in a group of EBVaGC that is traditionally considered highly immunogenic.
The ctDNA in peritoneal effusion of advanced gastric cancer for auxiliary diagnosis of peritoneal metastasis.
Authors: QI Changsong , Li Pansong , Hu Yanting , Chang Lianpeng , Wu Yi , Gong Yuhua , Gao Jing , Guan Yanfang , Zhang Xiaotian , Xia Xuefeng , Yi Xin , Shen Lin 
Published: May 2019

e15516 Background: Peritoneal metastasis (PM) is the most frequent mode of distant metastasis in advanced gastric cancer (GC). Most PM could cause peritoneal effusion. However, the cytological examination of cancer cells in peritoneal effusion is less sensitive to the identification of PM early; the specificity of serum biomarkers in peritoneal effusion is poor. It is necessary to assess the feasibility of peritoneal effusion circulating tumor DNA (ctDNA) for the PM diagnosis. Methods: 22 GCs with clinically confirmed PM as positive subjects and 11 non-cancers without PM as negative control were recruited. GC tissues were collected from 16 positive subjects. Peritoneal effusion supernatant (AS), peritoneal effusion cells (AC), and plasma were collected from each subject. Next generation sequencing (NGS) was performed using a 1021-gene panel. Sensitivity and specificity for the diagnosis of GC with PM were assessed. Results: Median age of 22 GCs with PM was 57 yrs. 12 patients were male. Diffused and mixed-type accounted for 73%. For 45% of patients, primary tumor was found in gastric body. In tissue samples, recurrent genes were TP53 (63%), CDH1 (50%), RHOA (19%), TGFBR1 (19%), KRAS (13%), and PIK3CA (13%). Private and tumor-derived mutations were found in the AS, AC, and plasma. 95% of (21/22), 82% (18/22), and 77% (17/22) of AS, AC, and plasma samples carried mutations, respectively. AS had more mutations than AC and plasma (Wilcoxon’s matched-pairs signed-ranked test, AS vs AC, p= 0.006; AS vs plasma, p = 0.013). 98% of the AC and 80% plasma mutations were contained in AS, Variant allele frequency (VAF) in AS was higher than others (Mann Whitney test, AS vs AC, p= 0.038; AS vs plasma, p< 0.001). In 22 GCs with PM, 3 were identified with no cancer cells in AS using cytological examination. Of these, 3 were detected with mutations in AS, one with mutations in AC. Mutations were detected in only one negative control AS and AC. Receiver operating characteristic (ROC) curve showed the number of mutations was related to PM (AS: AUC 0.93, 95% CI 0.82-1.00, p< 0.001; AC: AUC 0.85, 95% CI 0.70-1.00, p= 0.001). When the threshold was determined with one mutation, the sensitivity and specificity were 95% and 91% in AS, 82% and 91% in AC, respectively. Conclusions: Peritoneal effusion ctDNA contained tumor-derived and specific mutations. Peritoneal effusion ctDNA can be used for the auxiliary diagnosis of PM.
The prognostic factors associated with long-term survival in the patients with synchronous oligometastatic esophageal adenocarcinoma.
Authors: Iwatsuki Masaaki , Harada Kazuto , Wang Xuemei , Bhutani Manoop S. , Weston Brian , Lee Jeffrey H , Nguyen Quynh , Hofstetter Wayne Lewis , Thomas Irene , Rogers Jane E. , Baba Hideo , Ajani Jaffer A. 
Published: May 2019

e15523 Background: Patients with gastrointestinal cancer are increasingly being diagnosed with oligometastatic disease due to the development of sensitive imaging. Oligometastases (OLM) represent a clinical and anatomical manifestation of resistant localized cancer and/or metastases. However, oligometastatic disease is complicated by the lack of uniformity due to the heterogeneity of cancer, therefore, differing prognoses. The aim of this study is to identify the factors associated with long-term survival in the patients with synchronous oligometastatic esophageal adenocarcinoma (EAC). Methods: Between 2002 and 2016, of 1400 patients with EAC (esophagus and Siewert types I and II) treated at our institute, 233 patients initially diagnosed with stage IVB were enrolled. OLM was defined as only metastasized to one organ and less than 5 metastases. We retrospectively analyzed the association between clinicopathological factors and prognosis, especially focused on the pattern of metastases. Results: Eighty-five patients (36.5%) had OLM, and 148 (63.5%) had non-oligometastais (Non-OLM). The patients in OLM had significantly better overall survival (OS) than the patients in Non-OLM (p = 0.0001). Univariate analysis showed pattern of metastases (lymphatic OLM) and treatment method (consolidative local radiotherapy: CLT) were significantly associated with prognosis (p = 0.04 and 0.01, respectively). Multivariate analysis revealed that lymph node metastases (cN0-N1), number of metastasis (solitary) and treatment (CLT) were independent predictors for OS of patients with OLM. (p = 0.03, 0.01 and 0.001, respectively). In OLM patients, the patients with lymphatic OLM who received CLT had more favorable prognosis (5-years survival rate 25%). Conclusions: This study suggests that CLT is one of the promising modalities for oligometastatic patients with EAC, especially the patients with lymphatic OLM.
Tissue plasminogen activator in gastrointestinal adenocarcinoma: What is its role?
Authors: Maslov Andrey A. , Kit Oleg I. , Frantsiyants Elena M. , Kozlova Larisa S. , Dzhenkova Elena A. , Soldatkina Natalya V. , Tishchenko Irina S. , Tumanyan Sergey V. , Gevorkyan Yuriy A. , Samoylenko Nikolay S. , Aleynov V. I. , Milakin Anton G. , Poluektov Sergey I. , Gabrichidze Petr N. 
Published: May 2019

e15532 Background: The aim of the study was a comparative analysis of the tissue plasminogen activator activity (tPA-Ag and tPA-act) in adenocarcinoma of the esophagus (EA), stomach (SA), pancreatic head (PHA), sigmoid colon (SCA) and rectum (RA). Methods: Tissues of tumors, perifocal area (PA) and resection line tissues were studied by ELISA in 143 patients (38-74 years) with EC (n = 12, G2, T2-3N0-1M0), SC (n = 28, G2, T2-3N0-1M0), PHC (n = 46, G2, Т2-4N0M0), SCC (n = 31, G2, T2-3N0-1M0) and RC (n = 26, G2, T2-3N0-1M0). Statistical analysis was performed using the Statistica 10 program. Results: Tumor levels of tPA-Ag were the highest in SA: SA˃RA˃SCA˃EA˃PHA, but in EA, SCA and RA were lower than in the resection line (p < 0.01). Tumor levels of tPA-Ag in SA were similar to the values in PA, and were 3.1-213 times higher than in other tumors. Perifocal levels of tPA-Ag were the highest in SA: SA˃SCA and RA˃EA˃PHA, but in EA and PHA they were lower than in the resection line tissues (p < 0.01), in SCA and RA – similar, in SA – exceeded the levels in all samples by 1-2 orders of magnitude (p < 0.0001). Levels of tPA-Ag were similar in resection line tissues in SCA and RA, being 2.5-128 times higher than in other tumors. The highest tPA-act was observed in perifocal and tumor tissues in SA (p < 0.0001, compared to other tumors): SA˃SCA˃RA˃EA˃PHA (p < 0.01). tPA-act in PHA tumors was 1.3 times higher (p < 0.05) than in resection line tissues and 40.5 times lower than in PA. In SCA, tPA-act was similar in tumor and PA, but was 1.3 times lower (p < 0.05) than in resection line tissues. In RA, tPA-act decreased from the resection line to the tumor by 1.3 and 2.3 times, respectively. Conclusions: The role of tPA in gastrointestinal adenocarcinomas differs: in EA, SCA and RA it has protective functions, as its levels in the tumor are lower than in the resection line. SA was accompanied by an enhanced secretion of tPA-Ag and the formation of tPA-act in tumors, with their subsequent evasion into PA. In PHA, the tPA distribution was similar, but the high rate of tPA activation led to the depletion of both forms of tPA, while still retaining their advantage in the tumor and PA, compared with the resection line.
Prevalence of gastric cancer and premalignant changes in a Michigan cohort, 2013-2017.
Authors: Nemakayala Divyesh Reddy , Tatineni Shilpa , Enofe Ikponmwosa , Wang Ling , Laird-Fick Heather 
Published: May 2019

e15539 Background: Gastric cancer (GC) is uncommon in the US. Incidence varies by geography, race/ethnicity, sex, age, and socioeconomic status (SES). H. pylori is a risk factor for premalignant lesions and GC. Prior studies estimate risk of progression from premalignant to GC at 0.1-0.5% per year. US prevalence of premalignant lesions is unclear. This study describes the prevalence of premalignant lesions and GC in a large community-based sample. Methods: Patients aged ≥18 years undergoing EGD with gastric biopsy in Sparrow Health System were identified. Pathology reports were abstracted for sociodemographics, procedure information, and pathologic findings. Only patients with complete data were included for analysis. Statistical comparisons were assessed by chi-square tests or Fisher’s exact test in contingency tables for categorical variables, or t-tests for continuous variables as appropriate. Results: 4,111 patients were included for analysis. 3,783 (92.04%) had benign findings, 119 (2.90%) premalignant changes, and 31 (0.75%) gastric malignancies. 177 (4.31%) were H. pylori positive. Patients with benign (72.2%), premalignant (69.8%) and H. pylori-positive (69.5%) findings were often inpatients ( p< 0.001 for all comparisons), but not patients with GC (58%, p= 0.37). Benign findings and H. pylori were more common in females (69.3%, p< 0.001 and 59.9%, p< 0.001, respectively). There were no sex differences for premalignant or malignant lesions. Patients with premalignancy and malignancy were older than those with benign findings (mean age 61.6 (SD = 14.8) vs 54.9 (SD = 16.1) years, p< 0.001, and 69.9 (SD = 14.2) vs 54.9 (SD = 16.1) years, p< 0.001, respectively). There was no age difference between patients with benign changes or H. pylori (mean age 54.9 (SD = 16.1) vs 56.4 (SD = 14.4) years, p= 0.24). There were no differences in SES by histological subtype. Conclusions: In a community sample, premalignant lesions and GC were uncommon and did not vary by sex or income. H. pylori infection was also uncommon and varied by sex. This may reflect actual burden of infection or protocols for testing biopsy specimens. Understanding local prevalence of premalignant changes could inform resource planning and surveillance strategies.
Survival analysis and clinical characteristics of forty-eight patients with alpha-fetoprotein-positive gastric cancer treated by integrated Chinese and western medicine.
Authors: He Wenting , Zhang Tong , Xuan Yanhong , Zhang Hongliang 
Published: May 2019

e15550 Background: Alpha-fetoprotein-producing gastric carcinoma (AFPGC) is a special type of gastric cancer, which has characteristics of strong invasiveness, prone to liver and lymphnode metastasis, easy misdiagnosis and worse prognosis. According to the literature, the survival of AFPGC was 4-14 months (m). There is no report about integrated Chinese and Western Medicine on the AFPGC patients. This study is to explore the effect of integrated Chinese and Western Medicine on the survival and clinical characteristics of patients with AFPGC. Methods: 398 consecutive patients with gastric cancer admitted to Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine from Jan 2012 to Jun 2018 were retrospectively collected. All patients were diagnosed by pathology. And on the basis treatment of conventional Western Medicine combined with Chinese Medicine for more than 3 m. Follow-up up to Dec 31th 2018. The median follow-up time was 11.1 m. According to the results of serum alpha-fetoprotein chemiluminescence assay, AFPGC was found in 48 out of 398 patients. The median overall survival (mOS) and clinical characteristics of AFPGC patients were analyzed. Results: Among 48 patients with AFPGC, 1 case (2.1%) in stage Ⅰ, 1 case (2.1%) in stage Ⅱ, 8 cases (16.7%) in stage Ⅲ, 36 cases (75.0%) in stage Ⅳ, and 2 cases with unknown stages; 35 cases (72.9%) received chemotherapy, 22 cases (45.8%) received local treatment, including palliative radiotherapy and hepatic artery chemoembolization, and 4 cases (8.3%) received targeted therapy. At the end of follow-up, 40 patients died, with the mOS of 16 m, 27.5 m in stage Ⅰ-Ⅲ and 14 m in stage Ⅳ, which was significantly longer than reported in the literature. Compared with non-AFPGC patients, tumor metastasis and serosal invasion of higher incidence ( 75.0% vs 38.9, x2= 22.3, p < 0.0001; 75.0% vs 38.9%, x2= 17.5, p = 0.0015 ). The incidence of liver and/or lymph node metastasis is higher (52.1% vs 17.4%, x2= 25.1, p < 0.0001; 33.3% vs 15.7%, x2= 7.7, p = 0.0054 ). The incidence of pleuroperitoneal and omental metastasis is higher (33.3% vs 11.7%, x2= 13.0, p = 0.0003 ). Conclusions: Integrated Chinese and Western Medicine can significantly prolong the survival of patients with AFPGC. AFPGC seem to be more prone to tumour metastasis, serosal invasion, liver metastasis, lymph node metastasis, pleuroperitoneal and omental metastasis. However, limited by the sample size, whether the above factors are independent prognostic factors for AFPGC is still not conclusive.
Final results of early non-invasive gastric cancer detection study using the serum pepsinogen test method in Croatian patients.
Authors: Trivanovic Dragan , Plestina Stjepko , Honovic Lorena , Dobrilla-Dintinjana Renata , Tanaskovic Jelena Vlasic 
Published: May 2019

e15551 Background: Gastric cancer (GC) is the 8th most common cancer cause of cancer deaths in Croatia and 2nd most common cause of cancer deaths worldwide. GC of the intestinal type is usually preceded by a chronic atrophic gastritis which is a precancerous change in the stomach. Methods: A reliable diagnostic tool for the early detection of the GC is essential. Screening programs have led to an improvement of overall 5-y survival rate for GC in Japan and Pepsinogen test method was suggested to reduce mortality from gastric cancer. The gold standard for the diagnosis of GC is the pathohistological study of biopsies obtained during an upper GI endoscopy, an invasive method that is too complicated for use in population screening and patients with comorbidity. We have conducted a prospective single center clinical study over a period of > 2 years to evaluate sensitivity and specificity of reagents, and to determine if these reagents can be part of routine. Inclusion criteria for the study were: signed informed consent, life expectancy > 12, and exclusion criteria were: previous treatments for any malignancy, current usage of IPP or NSAIDs medication, poor ECOG performance status ≥3, known history of H. pylori eradication treatment or gastric surgery. We previously reported preliminary results of PG test method in Croatian population. Here, we present mature data after median follow-up of 26 months. Statistical analyses were performed by using a Mann-Whitney U test, multiple logistic regression and the receiver operating characteristics (ROC) to evaluate the predictive power of biomarkers. Results: Blood samples have been collected from patients with suspicious to GC attending for endoscopy or surgery. We used cut off points to evaluate gastric cancer risk: PGI ≤ 70 and PGI/II ratio ≤ 3.0. Of the 116 patients, 25 patients had GC and 91 had non-malignant pathology on tissue biopsy (like atrophic gastritis). Based on an optimal cut-off value calculated by ROC curve analysis had accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 86.2%, 60.0%, 93.4%, 65.2%and 89.47%, respectively, for the diagnosis of GC. AUC was 0.767 (95% CI 64.0-89.0). Conclusions: The single use of pepsinogen tests is not sufficient for stomach cancer detection; however, it provides a valuable test for selecting a population that needs further diagnosing. Meanwhile, its high specificity could also help to avoid unnecessary endoscopy, especially in older population or patients with heavy burden of comorbidity. Clinical trial information: 2016-0019-34.
Effect of p-PAQR3Thr32 on PD-L1 expression and immune evasion in gastric cancer.
Authors: Ling Zhi-Qiang 
Published: May 2019

e15571 Background: Therapies targeted to the immune checkpoint mediated by PD-1 and PD-L1 show antitumor activity in some solid tumors. We have now examined PD-L1 expression and its regulation in gastric cancer with p-PAQR3Thr32 protein. Methods: The expression of PD-L1 at the protein and mRNA levels in gastric cancer cell lines was examined by flow cytometry, real-time RT-PCR and western blot analysis, respectively. The expression of PD-L1 and p-PAQR3Thr32 protein in 319 surgically resected gastric cancer specimens was evaluated by immunohistochemical analysis. Results: The PD-L1 expression level was higher in gastric cancer cell lines positive for p-PAQR3Thr32 protein induced by glucose starvation than in those negative for the p-PAQR3Thr32 protein. Forced expression of p-PAQR3Thr32 protein in gastric cancer cells markedly increased PD-L1 expression, whereas endogenous PD-L1 expression in p-PAQR3Thr32 protein positive gastric cancer cells was attenuated by treatment with PAQR3 siRNAs. Furthermore, expression of PD-L1 was downregulated by inhibitors of the IRF1 and STAT1 in IFNs-PDL1 signaling pathway in gastric cancer cells positive for p-PAQR3Thr32 protein. At clinical tissue level, the expression level of PD-L1 was positively associated with the presence of p-PAQR3Thr32 protein in gastric cancer specimens. Moreover, the expression level of p-PAQR3Thr32 protein was negatively correlated with CD3, CD8, GZMA (CD8 T cell secretory factor) and positively correlated with CD68 (macrophage marker). Conclusions: Our findings that p-PAQR3Thr32 protein induced by glucose deficiency upregulate PD-L1 by activating IFNs-PDL1 signaling pathway in gastric cancer reveal a direct link between p-PAQR3Thr32 protein and PD-L1 expression. It is suggested that p-PAQR3Thr32 protein may be involved in tumor immunosuppression by inhibiting the proliferation and activity of CD8 T cells in gastric cancer tissues.
The impact of method of recurrence detection on esophageal/gastroesophageal junction (EGJ) cancer outcomes.
Authors: Matloubieh Jubin Eghbali , Licona-Freudensten Alexandra Pilar , Baran Andrea M , Dunne Richard Francis , Hezel Aram F , Noel Marcus Smith , Lada Michal J , Peyre Christian G , Jones Carolyn E , Tejani Mohamedtaki Abdulaziz 
Published: May 2019

e15580 Background: Trimodality treatment (tx) with neoadjuvant chemoradiation (CRT) followed by esophagectomy is standard tx for locally advanced EGJ cancer. Post-operatively, there is no strong consensus about role of routine surveillance imaging. At the University of Rochester, patients (pts) have surveillance CT scans every 4-6 months (mos) for the first 2 years post-esophagectomy and every 6-12 mos for the next 3 years. Methods: Pts were identified who underwent esophagectomy for T1-T3 EGJ cancer between January 2011 and December 2015 at our institution. Objectives were to describe the impact of timing and methods of recurrence detection (MoRD) on patient outcomes. Recurrence-free (RFS) and overall survival (OS) were graphed via the Kaplan-Meier method. Results: 138 pts underwent esophagectomy for EGJ cancer: 107 (77.5%) were male, median age was 64, and 116 patients (84.1%) had adenocarcinoma. 112 pts (81.2%) had neoadjuvant CRT. The entire cohort’s median OS was 38.4 mos. 68 pts (49.3%) relapsed with a median RFS of 20.0 mos. Recurrence was detected by routine imaging in 36 pts (52.9%), imaging triggered by symptoms in 27 pts (39.7%), and symptoms alone in 5 pts (7.4%). Post-relapse median OS was 2.3 mos when detected based on symptoms alone, 5.0 mos when detected by imaging triggered by symptoms, and 13.7 mos when detected by routine scans (log-rank p = 0.041). There was no significant association between baseline patient/tumor characteristics or pathologic response and MoRD . 53 patients (77.9%) received salvage/palliative tx with a median of 2 tx (IQR = 1). There was no significant association between MoRD and number of salvage/palliative tx. Conclusions: 49.3% of pts relapsed after esophagectomy for EGJ cancer, consistent with current literature. Almost half of relapses were detected based on symptoms despite routine imaging. Increased OS for pts with relapse detected by routine scans is likely related to lead time bias, but may also be related to increased tx intensity or less aggressive tumors. MoRD did not have a measurable impact on number of lines of post-relapse tx. Prospective randomized trials are needed to determine real benefit of regular surveillance scans among EGJ cancer survivors.