bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic value of serum CA 19-9 in patients with metastatic colorectal cancer.
Authors: Mosgaard Camilla Stedstrup , Holsey Gramkow Mathias , Dehlendorff Christian , Nielsen Dorte , Pfeiffer Per , Qvortrup Camilla , Yilmaz Mette K. N. , Larsen Ole , Bojesen Stig Egil , Schou Jakob Vasehus , Boisen Mogens Karsboel , Johansen Julia S. , Jensen Benny Vittrup 
Published: September 2018

e15131 Background: CEA is regarded as the marker of choice for monitoring patients with colorectal cancer (CRC), but the value of using CA19-9 is insufficient. The prognostic value of serum CA19-9 in combination with CEA was evaluated in patients with metastatic CRC (mCRC) before first (1) and third line therapy (3LT). Methods: From April 2004 to May 2015, pretreatment serum samples were collected from 160 and 255 patients with mCRC before 1LT and 3LT, respectively. Median age was 64 [range 33-87] and male/female ratio 243(59%)/172(41%). Serum CA19-9 was determined by routine chemiluminescent immunometric assay (normal range 0-37 KU/l). Progression-free survival (PFS) and overall (OS) crude, adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were estimated using Cox regression analysis. CA19-9 and CEA were included as log2-transformed continuous variables and adjustment included mutually between CA19-9 and CEA in addition to primary tumor location, sex and age. Results: In 3LT median pretreatment CEA levels were higher than in 1LT (59 µg/l [IQR 14-288] vs. 23[6-153] P < 0.01) while CA19-9 values were similar (112 KU/l [23-626] vs. 98[19-390]). In patients treated with 3LT univariate analysis showed that high levels of CA19-9 and CEA were associated with short PFS (CA19-9: HR = 1.06, 95% CI 1.02-1.10, P < 0.01; CEA: HR = 1.05, 1.00-1.09, P = 0.04). In 1LT neither CA19-9 nor CEA were significantly associated with PFS. In a multivariate analysis, none of the biomarkers were significantly associated with PFS. In patients treated with 3LT univariate analysis showed that high levels of CA 19-9 and CEA were associated with short OS (CA19-9: HR = 1.11, 1.07-1.16, P < 0.01; CEA: HR = 1.1, 1.06-1.16, P < 0.01). In patients treated with 1LT high levels of CA-19-9 but not CEA was significantly associated with a shorter OS (HR = 1.07, 1.00-1.14, P = 0.04). In 3LT multivariate analyses showed that high levels of CA19-9 and CEA were the only factors associated with a shorter OS (CA19-9: HR = 1.08, 1.03-1.13, P < 0.01; CEA: HR = 1.07, 1.01-1.14, P < 0.01), while there was no significant association to OS in 1LT. Conclusions: Serum CA19-9 may be a valuable prognostic biomarker in combination with CEA in mCRC patients receiving third line therapy.
Trends in biomarker testing among metastatic colorectal cancer patients: A temporal description of KRAS, NRAS, and BRAF testing in the EU5.
Authors: Lowe Kimberly , Niu Xin , Kafatos George 
Published: September 2018

e15136 Background: The European Medicines Agency (EMA) changed its indication language from wild-type KRAS to wild-type RAS ( KRAS and NRAS) for metastatic colorectal cancer (mCRC) patients treated with panitumumab in July 2013. The objective of this study was to describe patterns of KRAS, NRAS, and BRAF testing among mCRC patients in the EU5 (United Kingdom (U.K.), Germany, France, Italy and Spain) and to evaluate if there were demographic or clinical differences in the patients who were/were not tested. Methods: This descriptive study utilized a serial physician survey from Oncology Analyzer data (IMS Health Oncology, Fairfield, CT, USA), which provides real-world epidemiologic and clinical data. Trends in biomarker testing were evaluated by calculating the proportion of patients who were /were not tested for combinations of KRAS, NRAS, and BRAF within each of the five countries. KRAS and BRAF data were available in all countries from quarter three (Q3) 2012 to quarter two (Q2) 2015. NRAS was available in all countries from quarter 1 (Q1) 2014 to Q2 2015. Frequencies and proportions were also calculated to summarize patient demographic and clinical characteristics between groups with different testing choices. Results: The study included 32,961 mCRC patients. Prior to July 2013, most patients were tested for only KRAS. The proportions of patients tested for both KRAS and NRAS increased substantially during the period of data availability for NRAS, including < 1% to 19.1% in the U.K., 8.8% to 31.9% in France, 13.1% to 43.2% in Germany, 5.9% to 24.6% in Italy, and 8.7% to 31.4% in Spain. The proportions of patients tested for all three biomarkers also increased during the period of data availability for all three biomarkers (Q1 2014 to Q2 2015), including 2.3% to 16.4% in the U.K., 4.8% to 26.6% in France, < 1% to 2.4% in Germany, 4.2% to 22.3% in Italy, and 1.5% to 9.3% in Spain. There were few differences in patient demographic or clinical characteristics between those with different testing choices. Conclusions: This analysis provides a description of the patterns of biomarker testing using read-world data and suggests a consistent increase in testing among mCRC patients in the EU5.
Extramural venous invasion on pretreatment MRI and surgical pathology: Is there a role in predicting prognosis in rectal cancer?
Authors: Kamran Sophia C. , Kordbacheh Hamed , Baliyan Vinit , Hong Theodore S. , Kambadakone Avinash 
Published: September 2018

e15165 Background: Extramural venous invasion (EMVI) describes tumor cells invading the veins beyond the muscularis propria and has been previously recognized as a predictor for survival and disease recurrence in rectal cancer. EMVI is generally diagnosed on pathology after surgical resection. Pretreatment MRI has been proposed as a surrogate imaging biomarker for recognition of EMVI. Our objective is to study the prognostic significance of EMVI in rectal cancers based on pretreatment MRI imaging to determine its correlation with overall survival (OS), local recurrence (LR), and distant metastases (DM). We also compare MRI-detected EMVI to EMVI detected on pathology to evaluate correlation. Methods: In this ongoing study, records of rectal cancer patients with a pretreatment staging MRI diagnosed between 2004-2015 were retrospectively reviewed (n = 180). Pretreatment rectal MRIs were evaluated for different imaging characteristics, including EMVI. The endpoint of OS was calculated using the Kaplan-Meier method and compared with a log-rank test. A p< 0.05 was considered significant. Cox proportional hazard ratios for LR and DM were generated using clinical, imaging, and pathologic characteristics. Results: Most patients were male (63%) with a median age at diagnosis of 63 years (28.5-95.2). Eighty percent of patients received neoadjuvant chemoradiation (nCRT) followed by surgery and adjuvant chemotherapy (AC); 20% received nCRT followed by surgery. A pathologic complete response was achieved in 17% of patients. Median survival was 48.5 months (2.6-145.2); five-year OS was 85%. The receipt of AC improved OS (HR 0.40, CI 0.2-0.9). Of 70 patients with EMVI noted on the pretreatment MRI, 22 (31%) had EMVI on pathology (p = 0.05). EMVI on MR was not found to be prognostically significant for OS, LR, or DM. EMVI on pathology was found to be significant for DM (HR 3.74, CI 1.8-8.0). Conclusions: Preliminary results show that pretreatment MR-detected EMVI was not found to be predictive for OS, LR, or DM, but pathologically-detected EMVI was found to be a predictor for DM. Further analysis of the relationship between this surrogate imaging biomarker on post-CRT MRI and outcomes is ongoing.
Next-generation sequencing of esophageal carcinosarcoma to reveal high frequency of actionable PIK3CA gene mutations.
Authors: Lu Hongyang , Yang Shifeng , Jiang Zhiming , Xie Fajun , Qin Jing , Gong Lei , Han Na , Fan Yun , Mao Weimin 
Published: September 2018

e15503 Background: Esophageal carcinosarcoma (ESC) is a rare malignant esophageal neoplasm consisting of both carcinomatous and sarcomatous components. Drive genes mutations may potentially serve as novel biomarkers to targeted therapy in ESC, and they also may explain the mechanisms of the unique dual-differentiation pattern. Actionable gene alterations with any significant frequency in ESC were unknown due to specimen numbers and limited studies. A comprehensive study of clinical characteristic and molecular alterations in ESC is needed to better understand biology and guide therapy. Methods: Fifteen cases of ESCs which received surgical resection were retrospectively collected from the Zhejiang Cancer Hospital in China between 2009 and 2016, next generation sequencing was performed to identify genotypic changes, and clinical characteristic of these patients was also collected and analyzed. Results: ESC patients are easily occurred in male, heavy smokers, and old patients. The mainly gross types were medullary and fungating type. Mutation of phosphatase and tensin homologue ( PTEN), MAP2K1(MEK1), anaplastic lymphoma kinase ( ALK), RET, and NF1 were detected in one patient respectively. Mutation of ERBB2(HER2), MET and single copy loss of Rb1 were detected in two patients respectively. Mutation of ROS1 and phosphoinositide-3-kinase catalytic alpha ( PIK3CA) were detected in three patients respectively. Conclusions:PIK/AKT pathway may be important in pathogenesis of ESCs, and it may be an ideal therapeutic target.
Bolus infusion of cisplatin, 5-fluorouracil, and leucovorin as alternative first-line therapy for advanced gastric cancer.
Authors: Coelho Rafael Correa , Abreu Pedro Duarte , Monteiro Mariana Ribeiro , Stramosk Ana Paula , Gil Roberto Almeida , Siqueira Mariana , Pereira Bruno dos Santos Vilhena , Guedes Duque Cristiano , Palladino Alexandre de Mendonca , Graudenz Marcia Silveira , Andrade Carlos J C 
Published: September 2018

e15511 Background: Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death worldwide.Classic regimens in first line setting for advanced GC combine platinum compounds and fluoropirimidines ± antracyclines or docetaxel. At Brazilian National cancer Institute (INCA), there are limitations in hospital beds and infusion pumps, so the combination between cisplatin (CDDP) + 5-Fluorouracil (5-FU) in an infusion protocol has been out of possibility. An institutional project with an adapted protocol involving CDDP + 5-FU + Leucovorin (CFL) in bolus demonstrated good results and CFL became routine at INCA for more than 10 years. Methods: Retrospective cohort study evaluating 109 patients with advanced GC treated in first line setting with CDDP 80mg/m2(D1) + 5- FU 400mg/m2 (D1,D8,D15,D22)+ Leucovorin (LV) 20mg/m2 (D1,D8,D15,D22) in 28-day cycles from January 2008 to December 2014. Results: The median age was 54 years (24y-80y), 53.6% were male, 70% white and 20% mulatto, 49.1% formal smokers and 15.5% formal drinkers. Tumor staging at initial diagnosis was: E IIA 2.7%, E IIB 2.7%, E IIIA 1.8%, E IIIB 5.5%, E IIIC 5.5% and E IV 81.8%. Performance status ≤ 2 was present in 97.3% and G3 disease in 63.6%. The most common metastatic sites were: lymph nodes 31.8%, peritoneum 24.5%, liver 21.8% and lung 2.7%. The median of cycles received per patient was 4. Complete responses were achieved in 6.4%, partial responses in 14.5% and stable disease in 14.5%. Median PFS was 6.3 months (5.08 – 7.58) and median OS was 8.3 months (6.79 – 9.87). Seventy five (68.8%) patients were alive in 1-year and 26 (23.9%) in 2-years. Dose reduction was necessary in 9.1% and the most common toxicities were: nausea 27.3%, vomiting 19.3% fatigue 13.6%, diarrhea 10.6%, mucositis 4.2% and neutropenia 4.2%. Of all adverse events, grade 3 and 4 corresponded to 11.36% and 1.51%, respectively. Three patients had neutropenia G4. Only 26 patients (23.8%) received second line treatment. Conclusions: Chemotherapy protocol in bolus combining CDDP, 5-FU and LV could be an alternative for CDDP and 5-FU infusion protocol.
bghcng.
Authors: Castaneda Altamirano Carlos , Belmar Lopez Carolina , Castillo Garcia Miluska , Nieves Jais , Polo Julio , Chumpitaz Rodrigo , Gonzales Zoila , Bernabe Luis A. , Galvez Renato , Sanchez Joselyn , Payet Eduardo , Barreda Fernando , Chávez Iván 
Published: September 2018

e15521 Background: Helicobacter pylori (HP) infection is one of the most common infections worldwide and is a risk factor for gastric cancer (GC) development. This study was conducted to determinate the prevalence rate of HP as well as presence of vacA and cagA in gastric cancer samples from Peruvian patients. Methods: GC samples were prospectively collected from patients who went to surgery between April 2015 and November 2016. Three types of gastric samples were obtained from each patient: tumoral area (T), proximal healthy (P) and distal healthy tissue (D) samples. HP status through H&E was analyzed by a pathologist. DNA was extracted from tissue, and detection of colonization (ureA and hspA) and virulence genes (vacA and cagA) of HP was performed through quantitative PCR (qPCR). Results: A total of 183 patients were studied with a mean age of 64 years and 51.9% were men. 52.2% had a primary from antrum, 47.8% was HG 3 and 60% were diffuse. Presence of HP through H&E was found in 58.4% (n=107/183). Positive HP cases through qPCR were determinate with positivity of at least one ureA/hspA gene and was found in 89.6% (n=164/183). HP detection rate and its concentration were higher in D (ureA: 62.8%, n=115, [703.58±245.47pg]; hspA: 73.8%, n=135, [42.77±10.17pg]) than P (ureA: 59.0%, n=108, [539.69±121.32pg]; hspA: 71.0%, n=130, [31.90±8.64pg]) and T (ureA: 49.7%, n=91, [296.32±164.98pg]; hspA: 70.5%, n=129, [4.6±1.33pg]) (p<.001). Antrum location was associated to higher level of hspA expression (p=0.047). Neither histology (p=0.45) nor HG (p=0.2) was associated to level of hspA expression. qPCR detected HP in 75% (n=57/76) of cases without evidence of HP by pathology evaluation (H&E) (ICC: 0.77 vs 0.58). cagA virulence gene was detected in 95.8% (n=159/166) while vacAm allele in 85.5% (n=142/166) and vacAs allele in 96.8% (n=160/166). vacA+cagA- combination was found in 0.6% (n=1/166), vacA+cagA+ cases in 95.8% (n=159/166) and vacA-cagA- cases in 3.6% (n=3/166). Conclusions: Our results show a significant presence of HP in Peruvian gastric cancer patients and combination of vacA+/-cagA+/- virulence genes had particular patterns.
Whole-exome sequencing to identify HOMEZ mutation as a prognostic marker in esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy.
Authors: Luo Hong Lei , Jing Zhao , Xie Rui Fei , Wu Hong Jin , Zhang Xiao Yan , Zhang Hong Fang , Li Wen Xin , Hua Yu Hui , Wu Shi Xiu 
Published: September 2018

e15523 Background: The outcomes of inoperable esophageal squamous carcinoma (ESCC) patients treated with concurrent chemoradiotherapy remain poor. The discovery of novel biomarkers for predicting prognosis could allow for more accurate risk stratification and identification of high-risk patients. Although previous studies have elucidated some genomic alterations could be predictors of survival in these patients, none has focused on comprehensive genetic analysis using high-throughput platforms. Methods: Whole-exome sequencing was done in 96 inoperable ESCC patients treated with concurrent chemoradiotherapy from our phase Ⅲ clinical trial (NCT00686114). The prognostic marker was developed using a Random Survival Forest supervised classification methods based on log-rank splitting rules. The independence of the marker in survival prediction was evaluated by multivariable Cox regression analysis. The marker was further validated for the prognostic utility in an independent cohort (n = 150). The biological function of the genomic alteration was predicted by GO annotations. Results: A HOMEZ mutation (chr14:23744800_ACATCAT/ACAT) was detected in 54.1% of patients with ESCC received concurrent chemoradiotherapy. We identified the mutation was significantly associated with overall survival (hazard ratio [HR] 1.842; 95% confidence interval [CI] 1.080-3.142; P = 0.025) and loco-regional free survival (HR 3.008; 95% CI 1.302-6.947; P = 0.010). Multivariable Cox regression analysis showed that the mutation was also an independent prognostic factors for patients with ESCC (mutation type vs. wild type, overall survival: HR 2.161; 95% CI 1.241-3.764; p = 0·007; loco-regional free survival: HR 3.576; 95% CI 1.509-8.473; p = 0.004). GO annotations showed that HOMEZ tended to be frequently related to transcription factor activity, sequence-specific DNA binding and transcription corepressor activity. Conclusions: HOMEZ mutation is a novel independent prognostic factor for inoperable ESCC patients treated with concurrent chemoradiotherapy, and may be a potential therapeutic target.
Serum tumor markers to predict cancer-related venous thromboembolism in gastric cancer.
Authors: Yang Yan , Yang Yang , Shen Jie , Jie Xia , Yu Lixia , Qian Hanqing , Wei Jia , Du Juan , Liu Baorui 
Published: September 2018

e15526 Background: To investigate the relationship between the preoperative level of serum tumor markers and cancer-related venous thromboembolism in patients with gastric cancer. Methods: 1005 patients with gastric cancer who underwent curative resection were finally enrolled in this study. Serum tumor markers including CEA, CA19-9, CA242, CA72-4, CA125 were tested within one week before curative surgery. Measurement data between groups were compared with t test. The sensitivity, specificity, positive predictive values, and negative predictive values of five biomarkers and the combination group were calculated, respectively. The odds ratios were calculated via both univariate and multivariate logistic regression models. Results: Cancer-related venous thromboembolism was found in 540 (53.73%) patients. The increase of each cancer marker is remarkably related with cancer-related venous thromboembolism. The more abnormal serum tumor markers come out, the high the risk of positive cancer-related venous thromboembolism can be. The possibility of positive cancer-related venous thromboembolism would be 2.9 times as much as a normal patient as any of the tumor markers increases. With the increase of any 4 of the tumor markers can make the risk 16.4 times Conclusions: The status of postoperative cancer-related venous thromboembolism can be predicted from preoperative serum tumor markers. For those patients with a high risk of positive cancer-related venous thromboembolism, more aggressive treatment should be arranged.
RACK1 to modulate expression of MMP10 via Src/NF-κB pathway in gastric cancer.
Authors: Chen Ling , Chen Hao , Liu Fenglin 
Published: September 2018

e15529 Background: Receptor of activated C kinase 1 (RACK1) is regarded as a scaffolding protein in multiple intracellular signal transduction pathways. Our previous works had demonstrated that RACK1 might involve in progression of gastric cancer, and could be a criterion to predict the good prognosis for the patients after surgical resection. The aim of this study is to explore the regulatory role of RACK1 in matrix metalloproteinase 10 (MMP10) autocrine, and which may be involved in invasion of gastric cancer. Methods: RACK1 knockdown gastric cell lines were established by shRNA. Secretion of cytokines secretion, as well as MMP10 was measured by antibody arrays and enzyme-linked immunosorbent assay. Cell migration and invasion was compared between normal and RACK1 knockdown cells. Pharmacological inhibitors were employed in searching specific signaling pathway. The correlation of RACK1 and MMP10 expression in gastric cancer samples was analyzed by Spearman’s ρ test. Results: Expression of MMP10 was substantially enhanced after knockdown of RACK1 in vitro, which contributed to enhanced migration and invasiveness of gastric cancer cells in autocrine manner. Specific inhibitors of NF-κB and c-Src, as well as overexpression of dominant-negative c-Src mutant, could suppress the expression of MMP10. Finally, an inverse correlation of RACK1 and IL-8 expression was confirmed in gastric cancer samples. Conclusions: Down-regulation of RACK1 resulted in the up-regulation of MMP10 in gastric cancer, which might enhance invasiveness via Src/NF-κB pathway partially.
Risk factors associated with early postoperative complications following laparoscopic total gastrectomy: Experience from the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) group.
Authors: Liu Jingdong , Li Haojie , Zhao Gang , Xu Zekuan , Li Guoxin , Yu Peiwu , He Hongyong , Shen Kuntang , Liu Fenglin , Sun Yihong 
Published: September 2018

e15544 Background: The incidence rate of proximal gastric cancer has been rising steadily, and laparoscopic total gastrectomy (LTG) has been widely adopted. However, the safety of LTG still lacks solid evidence to prove. The aim of this study was to evaluate morbidity and mortality of LTG, and determine the risk factors associated with early postoperative complications. Methods: A retrospective multicenter study was carried out in China, and medical records of 109 gastric cancer patients receiving LTG during September 2014 and June 2016 were retrieved from the database. Patient characteristics, surgical outcomes, and postoperative morbidities and mortalities were analyzed. Results: Morbidity and mortality rates were 22.0% and 0% respectively. Pulmonary infection (13.8%, n = 15) was the most common complication. Most complications were grade II (15.5%, n = 17) according to the Clavien-Dindo classification. Multivariable analysis identified comorbidity, type of reconstruction method (TLTG) were independent risk factors of early postoperative complications. Comorbidity was the only independent risk factor of complications graded more than II. Diabetes mellitus was found correlated with surgical complication in subgroup analysis. Conclusions: LTG is safe and technically feasible in treating gastric cancer. Careful selection of patients without comorbidity and applying laparoscopy-assisted total gastrectomy instead of totally laparoscopic total gastrectomy may decrease postoperative complications.
Assessment of HER2 status in adenocarcinomas of the stomach or gastroesophageal junction in a Western population.
Authors: Martinez Lago Nieves , Padin Iruegas Maria Elena , Abdulkader Ihab , Santamaria Dora Insua , Carrera Juan Jose , Antunez Lopez Jose Ramón , López López Rafael 
Published: September 2018

e15548 Background: HER2 status is a predictive biomarker to response to trastuzumab in metastatic adenocarcinomas of the stomach our gastroesophageal junction. However, relatively little is known about the role of HER2 in the non-metastatic disease in western population. Methods: This study included 106 patients with gastric cancer who underwent surgery between January 2007 and June 2014 at Universitary Hospital of Santiago de Compostela. Immunohistochemical expression of HER2 was analyzed using the DAKO-HercepTest™ and gene amplification using DAKO-DuoCISH kit; both was scored according to published reports. Correlations between HER2 status, clinicopathological characteristics, survival and relapse sites were retrospective analyzed. Results: HER2 expression rate by IHC was: 76 patients (71.7%) classificated as negative, 7 patients (6.6%) as positive and 23 patients (21.7%) as equivocal. HER2 gene amplification by DuoCISH was positive in 14 patients (13.2%). HER2 status was associated with intestinal subtype (p = 0.010), tumor grade (well-moderately differentiated, p = 0.008), lower tumor invasion (p 0.018) and distant relapse (p = 0.048). There was a significant interaction between HER2 status and significantly worse disease-free survival (DFS) (P = 0.039) and overall survival (OS) (P = 0.028), respectively. Conclusions: In our population, HER2 status appears to be associated with differentiated clinicopathological characteristic, worse OS and DFS and distant site of relapse in patients with resected gastric cancer.