bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione system to characterize the biological aggressiveness of the gastric cancer.
Authors: Shalashnaya Elena V. , Goroshinskaya Irina A. , Surikova Ekaterina Igorevna , Medvedeva Dar'ja E. , Kachesova Polina S. , Nemashkalova Ludmila A. , Neskubina Irina Valerevna , Maslov Andrey A. , Kit Oleg I. 
Published: September 2018

e15512 Background: The aim was a comparative study of glutathione system of tumor and its peritumoral tissues at gastric signet ring cell carcinoma (SRCC) and gastric adenocarcinoma (AC) to identify pathogenetic features of malignancy. Methods: Content of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST) were determined in the samples of tumor and peritumoral tissues, obtained during the surgery in 21 primary patients: 13 patients with SRCC, 8 patients with AC (G2-G3) without preoperative therapy. Tissue of intact stomach was studied in 12 randomly bereaved. Results: In the AC tumor tissue the GSH level was decreased by 43% and the activity of GPx and the GST was increased by 121.7% and 44.3% (p < 0.05–p < 0.001) compared with intact stomach. In peritumoral tissue both the level of GSH and GPX activity were less than in the tumor tissue at 40-45% (p < 0.05–p < 0.01). In SRCC both the GSH level and the activity of GPx and GST were increased in tumor tissue by 78%, 93.6% and 49.5% (p < 0.05–p < 0.001) compared with the intact stomach. In peritumoral tissue the GSH level was lower than in the tumor tissue by 60.2% (p < 0.01), the enzymes activity was unchanged remaining higher than in the intact stomach. The GSH level both in tumor and in peritumoral tissues was 2-3 folds higher in gastric SRCC than in AC. No significant differences in the activity of glutathione-dependent enzymes in tumors of different histotype were revealed. Conclusions: The results show the differences in the functioning of the glutathione system, depending on the histological type of gastric tumors. It is possible that greater activity of glutathione-dependent system in tissue of SRCC is needed to maintain its increased proliferative activity and determines the features of the biological behavior of this tumor histotype.
Radiation esophageal stent.
Authors: Herskovic Arnold M. , Rivard Mark , Rothstein Richard I , Hussein Zella , Saunders Jennifer , Corcoran Kathleen , Clerc Claude , Favreau John 
Published: September 2018

e15514 Baclground:Self-expanding metal stents (SEMS) produce palliative dysphagia relief for esophageal cancers (EC) which is enhanced by brachytherapy. We present a brachytherapy stent designed to deliver radiation to ECs with brachytherapy sources in the porcine esophagus. Methods: A radioactive carrier stent containing I 125 seeds was designed to deliver 60 Gy to 5mm depth over 2 months. One dummy,non-radioactive seeds, and 3 radioactive stents were implanted into the esophagus of Yucatan minipigs. Stents were left in place for up to 43 days after implant, and one pig survived 10 weeks after stent removal. Animals were monitored biweekly via endoscopy and fluoroscopic imaging throughout the study collecting tissue at necropsy. Results: Swine esophageal tissue received doses ranging from 39-48 Gy at the prescription depth of 5mm and 132-160 Gy at the mucosal surface. Tissues were assessed pathologically at 0, 1, and 10 weeks after stent removall. Endoscopic assessment of all irradiated animals found increasingly pronounced and permanent infolding of the proximal stent flare over time, eventually resulting in early stent removal. At stent removal, all animals had numerous benign mucosal polyps ( < 5mm) at both stent flares which mostly resolved. within 6 weeks of removal, At gross necropsy, small amounts of necrotic tissue as well as mucosal polyps were observed along the entire length of the tissue adjacent to the radioactive stent (mostly adjacent to the stent flares). No systemic effects related to radiation were observed. Conclusions: We demonstrated that brachytherapy stent delivery is feasible and reasonably safe for irradiated healthy tissue. Although irradiation > 130 Gy affected the mucosal tissue, stent-related injury appeared to cause more substantial damage to the tissue. Both experimental and control animals showed the most marked tissue reaction at the non radiative stent flares. Tissue reactions along the stent body were consistent with stent related tissue erosion possibly enhanced by radiation exposure, . One animal, assessed up to 10 weeks after stent removal showed nearly complete healing of the esophageal tissue. Future studies will assess safety in a larger cohort of animals with escalated RT doses and different radionuclides.
Study of microflora in stomach cancer and gastritis.
Authors: Zykova Tatiana , Kit Oleg Ivanovich , Gevorkyan Yuri , Legostaev Vladislav , Bogomolova Olga A. 
Published: September 2018

e15516 Background: The purpose of the study was to compare the rates of bacterial and fungal colonization of the mucosa in stomach cancer and gastritis. Methods: 59 tumor and healthy tissue samples in stomach cancer and 33 stomach mucosa bioptates in gastritis were studied. DNAs were extracted by the adsorption method. DNAs of Enterobacteriaceae, Staphylococcus spp., Streptococcus spp., Candida spp., Bacteroides spp. were determined by real-time PCR. Results: 40.0% of 30 patients with stomach cancer had adenocarcinoma, 13.3% – signet ring cell carcinoma, 6.7% – undifferentiated cancer, 6.7% – NHL, 3.3% – squamous cell carcinoma, 6.7% – combined signet ring cell carcinoma and neuroendocrine or undifferentiated cancer, 23.3% – combined adenocarcinoma and neuroendocrine, signet ring cell or undifferentiated cancer. The comparison group included 33 patients with morphologically verified superficial gastritis. DNA of Bacteroides spp. was found in tumor and healthy tissues of 80.0% of cancer patients; it was not found in gastritis. DNA of B. fragilis was found in all tumor tissue samples, BFT – in 8.3% of them. The mean amount of Enterobacteriaceae in tumor tissue was 6.7x105 copy/ml, in healthy tissue – 7.0x105 copy/ml, in bioptates in gastritis – 4.0х102 copy/ml; Staphylococcus spp. – 3.4х102 copy/ml, 2.6х102 copy/ml and 8.7х101 copy/ml, Streptococcus spp. – 9.1х105 copy/ml, 1.3х105 copy/ml and 5.1х103 copy/ml, respectively. Thus, the amount of Enterobacteriaceae in tumor tissue in stomach cancer exceeded the value in gastritis by 1675 times, Staphylococcus spp. – by 3.9 times, Streptococcus spp. – by 178 times. Genes of resistance to the penicillin class TEM were found in 50.0% of patients with stomach cancer and in 8.7% of patients with gastritis. DNAs of Candida spp. in stomach cancer were found in 40% of patients in tumor tissue and in 31.0% in healthy tissue, in gastritis – in 8.3% of patients. Conclusions: Enterobacteriaceae and Streptococcus spp., mostly combined, dominate among microflora colonizing gastric mucosa in stomach cancer. The established differences in microbiocenosis in stomach cancer in comparison with gastritis suggest the possible involvement of aerobic and anaerobic microflora in the process of malignant transformation.
A preoperative nomogram for tumor regression grade following induction chemotherapy for esophageal squamous cell carcinoma.
Authors: Kang Xiaozheng , Dai Liang , Yan Wanpu , Yang Yongbo , Zhou Haitao , Fu Hao , Yang Heli , Fan Mengying , Lin Yao , Liang Zhen , Xiong Hongchao , Chen Ke-Neng 
Published: September 2018

e15525 Background: To (1) evaluate the continuous distribution of tumor regression grade (TRG) in resection specimens after induction chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC), (2) determine the effects of TRG on survival after esophagectomy, and (3) identify preoperative predictors of TRG. Methods: From June 2001 to October 2012, 212 patients underwent induction chemotherapy followed by esophagectomy for locally advanced ESCC. TRG, assessed as the percentage of residual primary ESCC cells in resection specimens, was classified histologically by pathologists. Random Forest technology was used for data analysis. A nomogram was developed allowing prediction of TRG through use of preoperative clinical factors for patients with clinically locally advanced ESCC who are candidates for treatment with a radical esophagectomy. Results: Twenty-four specimens (11%) had no residual primary cancer (ypT0), 39 (18%) had 1% to 10% residual cancer, 48 (23%) had 11% to 50%, 101 (48%) had more than 50%. Survival was worse with increasing residual primary ESCC, plateauing at 50%. Poorer TRG was associated with worse 3-year overall survival. Better pathologic grade (G), larger number of pack year smoking, fewer cycles of induction chemotherapy, lower level of creatinine, younger age, greater tumor length and clinical T stage were associated with poorer TRG. Conclusions: Better TRG in response to preoperative chemotherapy is associated with a linear increase in survival after esophagectomy for locally advanced ESCC. A nomogram has been developed that can be used to predict TRG. Therefore, for patients with poorer TRG, the role of adjuvant therapy needs to be further assessed in an attempt to improve survival.
Is third-line chemotherapy routine practice in recurrent or metastatic gastric cancer?
Authors: Lee Hyun Woo , Choi Yong Won , Ahn Mi Sun , Kang Seok Yun , Choi Jin-Hyuk 
Published: September 2018

e15558 Background: Patients (pts) with recurrent or metastatic gastric cancer eventually experience disease progression during or after completion of first-line chemotherapy. Second-line therapy is generally recommended in the current guidelines. Although third-line therapy is often performed in daily practice in some countries, there are few reports about the benefit of third-line therapy. Methods: A retrospective review was conducted on 683 pts who underwent at least first-line palliative chemotherapy for recurrent (n = 297) or primary metastatic (n = 386) gastric cancer. Clinicopathological characteristics and overall survival (OS) were analyzed according to the lines of chemotherapy as well as for all study pts. Results: One hundred and forty-nine pts (21.8%) underwent third- or further-line therapy. Third- or further-line therapy was more frequently performed in pts with young age ( < 70) (p < 0.0001), ECOG PS 0 or 1 (p < 0.0001) at the initiation of first-line therapy, first-line combination regimen (p = 0.006), and palliative surgical resection before first-line therapy (p = 0.029). The median follow-up duration was 62 months (24-151 months) for the survivors. The median OS for pts after first- and third-line therapy was 10 and 6 months, respectively. The median OS of pts who received third-line therapy was significantly longer than that of pts who received second- or lesser-line therapy (18 vs. 8 months, p < 0.0001). Multivariate analysis revealed that third- or further-line therapy was independently associated with favorable OS (hazard ratio = 0.56, p < 0.0001) along with surgical resection (p < 0.0001) and first-line combination regimen (p = 0.008), whereas signet ring cell histology (p = 0.002) and peritoneal metastasis (p = 0.027) were independent prognostic factors of poor OS. Conclusions: This study suggests that recurrent or metastatic gastric cancer pts may benefit from third-line chemotherapy, although careful selection is essential.
Esophageal cancer in elderly patients: A population-based study.
Authors: Zeng Yuan , Liang Wenhua , He Jianxing 
Published: September 2018

e15561 Background: As the aging issue and increased elderly esophageal cancer (EC) patients, we sought to study the clinical characteristics, treatment modality and outcomes of EC patients 70 years or older compared with those younger than 70 years old. Methods: The national Surveillance, Epidemiology, and End Results (SEER) database for the period from 1973 to 2013 was analyzed. The patient and treatment characteristics were compared between the age groups. Multivariate Cox proportional hazard regression analyses were also performed to identify independent prognostic factors. Propensity-score matching analyses (PSA) regarding survival after different treatments were also performed in locoregional EC . Results: Of 61,799 eligible patients, 24,046 patients (38.9%) were 70 years or older and 37,753 patients (61.1%) were younger than 70 years. Compared with the younger group, patients 70 years or older were characterized by having a higher proportion of patients with female gender, white race, localized disease, non-ademocarcinoma and without any treatment, as well as inferior overall survival (HR, 1.324) and EC-specific survival (HR, 1.270). In addition, older patients shared same independent prognostic factors with younger patients, including age, histology and race. Specifically, compared with those receiving no intensive treatments, surgery alone (HR, 0.342), both surgery and RT (HR, 0.323) and RT only (HR, 0.525) were favorable among elderly patients, as confirmed by both multivariate adjustment and PSA. Conclusions: Compared to younger EC patients, those 70 years or older showed distinctive clinical characteristics and inferior survival. Despite showing a higher proportion of localized disease, patients 70 years or older were less likely to be subjected to surgery or/and RT. Thus, the role of intensive treatments, which were identified as favorable factors among elderly patients in this study, warrants further investigation.
The potential prognostic value of expression of stem cell marker of CD44s, EpCAM, and OVA66 in patients with gastric adenocarcinoma.
Authors: Yan Ning , Xu Ying chun , Zhang Fengchun , Chen Siyu 
Published: September 2018

e15562 Background: The present study aimed to (i) examine the expression pattern of putative stem cell markers, CD44s, EpCAM, and new tumor specific antigen OVA66, in gastric adenocarcinoma (GA) and normal para-cancer tissues; (ii) determine if the expression of these proteins is associated with overall survival of GA. Methods: 84 GA patients confirmed by histopathology were examined the expressions of CD44s, EpCAM and OVA66 using tissue microarray technique. The immunohistochemistry analysis were carried out to explore the differential expression CD44s , EpCAM and OVA66 in GA compared to normal para-cancer tissues (p = 0.001). Next, Kaplan-Meier analysis was conducted to investigate their effect in overall survival(OS). Results: The immunohistochemistry analysis demonstrated the differential expression CD44s and EpCAM in GA compared to normal para-cancer tissues (p = 0.001), while there was no significant difference of OVA66 expression between cancer and normal specimens (p = 0.366). The upregulated expression of CD44s was well correlated with lymph node metastasis (p = 0.018), however the expression of OVA66 was only associated with gender of the patients (p = 0.025) and age at presentation (p = 0.018). The univariate analysis demonstrated that patients with blood and lymphatic vessel invasion, pT category 3 to 4, pN positive, with faraway metastasis, and stage Ⅲ to Ⅳ had a significantly shorter OS. Both increased expressions of the CD44s and EpCAM was shown in patients with poor OS (p = 0.037) and was confirmed by multivariate analysis. Conclusions: Our study suggested EpCAM is a potential diagnostic marker for gastric cancer and combined with CD44+/EpCAM+ can be regarded as an independent prognostic marker for patients with GA.
PDL-1 and immunohistochemistry markers in esophageal adenocarcinoma.
Authors: Jaroszewski Dawn E. , Xiu Joanne , Gatalica Zoran , Beamer Staci , Stanton Melissa , Pai Rish , Krishna Murli , Thomas Mathew , Ross Helen J. , Ho Thai Huu 
Published: September 2018

e15567 Background: Esophageal adenocarcinoma (EAC) prognosis is poor and there is a need to identify patients that benefit most from neoadjuvant therapy. To examine the association of various biomarkers with clinical outcomes in neoadjuvant treatment of EAC, we retrospectively evaluated the biomarker expression (TS, ERCC1, TOPO1, PD-L1, PD-1) in patient matched formalin-fixed paraffin-embedded (FFPE) tumor samples. Methods: Immunohistochemistry of TS (TS106/4H4B1) , ERCC1 (Ab. 8F1), TOPO1 (1D6), PD-L1 (both 22c3 and SP142), PD-1 (NAT105), and chromogenic in-situ hybridization (CISH) of Her2 were performed on FFPE samples from 35 patients across 2 institutions at time of EAC diagnosis and after treatment when available. Retrospective clinical data and survival (5/2006-1/2016) was analyzed with a mean follow up of 110 months (range 22-306). Results: Overexpression (pre/post-treatment) of TS (60%/54%), ERCC1 (69%/16%), TOPO1 (74%/50%), PD-1 (54%/63%), PD-L1 (SP142) (2.9%/4%), PD-L1 (22c3) (0%/4%) and amplification of Her2 (18%/23%) were observed. Pretreatment observed PD-L1 levels were lower in our study (3%) when compared to other studies in EAC specimens (35%). Immunohistochemistry and changes observed after chemoradiation are reviewed in Table. No markers had significant correlation with prognosis however TS negative expression showed a non-significant (p=0.15) trend towards improved survival. Conclusions: Analyzing biomarkers in our neoadjuvant EAC cohort demonstrated a lower than expected PD-L1 positivity. In the largest cohort, to our knowledge, of patient matched FFPE tumor samples, we did not observe a statistically significant association between TS, ERCC1, TOPO1, PD-L1, or PD-1 with improved clinical outcomes. [Table: see text]
How to improve the lymph node detection and staging accuracy in gastric cancer patients: A randomized controlled trial in single center.
Authors: Yao Zengwu , Jiang Lixin 
Published: September 2018

e15577 Background: To evaluate the effects of carbon nanoparticles by subserosa injection and different Lymph node retrievals by surgeon or pathologist in improving the positive and total lymph node detection and staging accuracy in patients who undergone the standard D2 gastrectomy. Methods: We collected 200 gastric cancer patients who undergone the standard D2 radical lymph node resection gastrectomy from November 2013 to November 2014 in Gastrointestinal Surgery Ward of Yantai Yuhuangding Hospital. The cases were randomly devidided into 4 groups (N = 50): Pathologist group(PA), surgeon group(SU), surgeon plus carbon nanoparticles group(SU+CN), pathologist plus carbon nanoparticles group (PA+CN) . The number of lymph nodes and the proportion of TNM stages were calculated respectively. Results: In the positive and total number of lymph nodes in all cases, it is significantly higher in Group SU than Group PA (3.64±4.32 VS 2.63±3.45),( 25.46±5.24 VS 20.23±6.32),Group SU+CN than Group PA (4.56±3.86 VS 2.63±3.45 ),(30.76±8.42 VS 20.23±6.32), Group PA+CN than Group PA(3.83±2.09 VS 2.63±3.45),(24.98±6.01 VS 20.23±6.32), Group SU+CN than Group SU(4.56±3.86 VS 2.63±3.45),(30.76±8.42 VS 25.46±5.24), Group SU+CN than Group PA+CN(4.56±3.86 VS 3.83±2.09),( 30.76±8.42 VS 24.98±6.01) (P < 0.05). The proportion of each TNM stage is significantly different in Group SU VS Group PA, Group SU+CN VS Group PA, Group PA+CN VS Group PA, Group SU+CN VS Group SU, Group SU+CN VS Group PA+CN(P < 0.05), while it is similar in Group PA+CN VS Group SU(P < 0.05). The highest proportion of Stage I and II and the lowest proportion of Stage III is in Group PA, and in Group SU+CN by contrary. Multivariate analysis shows carbon nanoparticles by subserosa injection and lymph node retrievals by surgeon are independent factors. Conclusions: Carbon nanoparticles by subserosa injection and lymph node retrievals by surgeon could be used as independent factors to improve the number of positive and total lymph nodes in standard D2 radical lymph node resection gastrectomy. It may also improve the accuracy of pathological staging of gastric cancer patients. Clinical trial information: ChiCTR-TRC-14876411.
Molecular profiling-guided therapy in gastroesophageal carcinoma: A single-institution experience.
Authors: Kankeu Fonkoua Lionel Aurelien , Liao Jason , Yee Nelson S. 
Published: September 2018

e15582 Background: Gastroesophageal carcinoma (GEC) including carcinoma of stomach (GC), gastroesophageal junction (GEJ), and esophagus (EC) is the 2nd leading cause of cancer death worldwide. Chemotherapy and HER2-targeted therapy (trastuzumab) have shown limited efficacy. We aim to assess the impact of molecular profile (MP)-guided therapy (MPgt) by correlating expression of select biomarkers in GEC patients (pts) with survival. Methods: 27 GEC (11 GC, 9 GEJ, 7 EC) submitted to Caris Life Sciences for molecular profiling between 2011 and 2016 were analyzed and correlated with pt survival. The impact of MPgt was assessed by calculating the ratio of progression-free survival (PFS) on MPgt to PFS on the preceding empiric therapy. MPgt was deemed beneficial if PFS ratio ≥1.3. Results: In-situ hybridization indicated amplification of HER2 (15.4%) and c-MET (7.4%). Immunohistochemistry revealed increased expression of TOPO1 (57.7%), TOP2A (38.5%), HER2 (15.4%) and c-MET (6.9%), as well as decreased expression of TS (69.2%), ERCC1 (42.3%), and PGP (15.4%). These data suggest sensitivity to topoisomerase inhibitors, anthracyclines, trastuzumab, MET-targeted therapy, fluoropyrimidine, platinums, and taxanes, respectively. Expression of these markers was heterogeneous among pts, and a trend toward improved PFS was noted in pts with low/absent ERCC1 expression on platinum-based therapy ( P= 0.06). Of the 13 pts who had sufficient data to assess the benefit of MPgt, 5 (38%) achieved a PFS ratio ≥1.3. One pt with metastatic HER2-amplified EC who had initially demonstrated clinical benefit from trastuzumab-containing chemotherapy, developed a new HER2 and c-MET co-amplified lung metastasis. Conclusions: While MPgt was beneficial in 38% of pts, tumor-associated plasticity, clonal evolution, and adaptive resistance may have limited efficacy. The emergence of HER2 and c-MET co-amplified clones is a potential resistance mechanism in HER2-amplified GEC, and highlights combined inhibition of receptor tyrosine kinases as a therapeutic strategy. Further studies with expanded data sets will be needed to test the hypothesis that actionable targets can be used independently to predict treatment response in GEC pts.