bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophil-to-lymphocyte ratio (NLR) to predict the short-term and long-term outcomes of gastric cancer patients.
Authors: Miyamoto Ryoichi , Inagawa Satoshi , Sano Naoki , Tadano Sosuke , Yamamoto Masayoshi 
Published: September 2018

e15560 Background: Preoperative NLR was well known as highly repeatable, cost-effective and widely available long-term postoperative prognostic marker of gastric cancer patients. However, the utility of preoperative NLR to predict short-term outcomes in gastric cancer patients remains unclear. In this study, we addressed whether the preoperative NLR is a predictive value of short-term outcome in gastric cancer patients. Methods: We retrospectively evaluated 154 consecutive gastric cancer patients. Mean NLR was calculated, and 3.5 was set as cut-off value. The patient characteristics and perioperative outcomes were respectively compared. In addition, median survival times (MSTs) were also compared. In terms of stage II/III (UICC 7th) gastric cancer patients, median disease-free survival times (MDFSTs) were compared between the two groups. Results: The patients were then divided into two groups: low-NLR group (n = 110) and high-NLR group (n = 44). Among low-NLR group and high-NLR group, significant differences were respectively observed in preoperative symptoms [56 (51%) vs. 31 (70%); p = 0.027] and perioperative outcomes including postoperative complications [3 (2.7%) vs. 5 (11.3%); p = 0.015], intraoperative blood loss (158 ± 168 g vs. 232 ± 433 g; p = 0.022), and intraoperative blood transfusion [0 vs. 3 (6.8%); p = 0.042]. MSTs and MDFSTs were significantly differed (812 vs. 594 days; p = 0.04, 848 vs. 475 days; p = 0.03, respectively). Conclusions: The present study indicated that preoperative NLR influenced not only long-term outcomes but also perioperative outcomes in gastric cancer patients. Preoperative NLR is also a useful predictive value of short-term outcomes in gastric cancer patients.
A study of thymidylate synthase gene expression as a biomarker for the treatment of esophageal adenocarcinoma.
Authors: Beamer Staci , Gatalica Zoran , Xiu Joanne , Jaroszewski Dawn E. , Stanton Melissa , Pai Rish , Krishna Murli , Thomas Mathew , Ross Helen J. , Ho Thai Huu 
Published: September 2018

e15563 Background: Expression of thymidylate synthase (TS), a target of fluoropyrimidine-based (5-FU) chemotherapy, has prognostic value in colorectal adenocarcinoma. Its value as a biomarker in treatment of esophageal adenocarcinoma (EAC) is unknown. With widespread adoption of CROSS trial protocol for treatment of EAC, 5-FU is frequently omitted from regimens. We retrospectively analyzed the association between TS protein expression and clinical outcomes in EAC. Methods: TS expression levels were measured by immunohistochemistry in formalin-fixed paraffin-embedded specimens from 35 primary EAC patients from 2 institutions (range 5/2006-1/2016); at time of diagnosis and surgical resection (33 neoadjuvant chemoradiation and 2 surgery alone). TS expression higher than 1+, 5% was read as positive. Mean follow up was 1323 days (range 263-3677). TS expression correlated with treatment response and survival in patients treated with and without 5-FU therapy (log-rank test, Kaplan-Meier method). Results: In the cohort of 35 patients, 21 patients (60%) had pretreatment positive TS expression. Overall survival (OS) for TS negative patients was 1216 days versus 974 days for TS positive (p = 0.15). In the 23 patients treated with 5-FU, TS-negative patients had a trend towards longer overall survival compared to TS-positive patients, mean OS (1272 days versus 743 days, p = 0.08). In the group of 12 patients not treated with 5-FU, 2 patients showed negative TS staining. Neoadjuvant chemoradiation was performed in 33/35 patients. Downstaging was observed in 69% (9/13) of patients with negative pre-treatment TS levels versus 55% (11/20) in pre-treatment TS positive patients (p = 0.48). In 23 patients treated with 5FU, 9/12 (75%) were downstaged in the TS-negative cohort versus 6/11 (45%) in the TS-positive cohort (p = 0.21). In the 5FU treatment group, complete response was seen in 2 patients with negative TS staining. Conclusions: Low TS expression in EAC patients trended towards improved survival and tumor downstaging, particularly in patients treated with neoadjuvant 5-FU and platinum based therapy. Prospective data and greater patient numbers may be necessary to demonstrate statistical significance.
The characteristics of c-MET and HER2 expression in gastric carcinoma and its correlation with clinical-pathological parameters.
Authors: Stuebs Patrick , Dittmar Florian , Zierau Kathrin , Fahlke Joerg , Ridwelski Karsten , Geers Ann Kristin , Lessel Jana , Jechorek Doerthe 
Published: September 2018

e15566 Background: The aim of this study was to determine whether overexpression of c-MET or HER2 had an effect on the clinical-pathological parameters and / or the prognosis of gastric carcinoma, as well as a direct correlation among those parameters. Methods: 134 gastric resectates were archived between 2007-2012 and retrospectively examined for c-MET and HER2 expression via immunohistochemistry (IHC). The HER2 status IHC2 + was additionally verified by means of Chromogenic in situ hybridization (CISH). Statistical data analysis was performed on the basis of the parameters acquired in the prospective multicentre observation study QCGC'07 / 09. Results: A total of 71 patients (53%) were found to express c-MET low and 63 patients (47%) expressed c-MET high, 122 patients (91%) were found to be HER2 negative and 12 persons (9%) were HER2 positive. C-MET high was significantly more pronounced in the Lauren intestinal type (63.8%, p = 0.001) and moderately to poorly differentiated tumour tissue (G2 50.9%, G3 43.9%, p = 0.038) as well es tissue with lymph vessel infiltration (L1 59.1%, p = 0.039). HER2 showed no significant effect on the clinical-pathological parameters. The median overall survival was shown to be shortened for the c-MET high-expressing (c-MET low 56 months, SD: ± 24.67; 95% CI: 7.65-104.36 vs. c-MET high 32 months, SD: ± (median-OS HER2 negative 38 months, SD: ± 14.11, 95% CI: 10.35-65, p = 0.839), and HER2 negative, 65, median-OS HER2 positive not reached, p = 0.305) patients. 8/134 resectates (5.97%, p = 0.135) were high and positive in both expression patterns, showing no significant difference to the OS (p = 0.393). Conclusions: In our studies, c-MET high or HER2 negative expression was associated with a poorer OS. However, no direct correlation between HER2 and c-MET could be demonstrated
Phase I study of the anti-PD-1 antibody SHR-1210 in patients with advanced solid tumors.
Authors: Huang Jing , Mo Hongnan , Wu Dawei , Chen Xuelian , Ma Lanying , Lan Bo , Qu Dong , Yang Qing , Xu Binghe 
Published: September 2018

e15572 Background: SHR-1210 is a humanized anti-PD-1 IgG4 antibody that blocks the binding of PD-L1 and PD-L2 to PD-1. SHR-1210 binds to PD-1 with high affinity. Methods: This phase 1 study consisted of dose-escalation and expansion cohorts. We used a standard 3+3 design to assess safety in the dose escalation part. SHR-1210 was initially administered by intravenous (IV) infusion over 30 minutes on days 1 and 28, and repeated every 14 days thereafter. Based on pharmacologic models, disease-specific cohorts were enrolled to receive SHR-1210 at 200 mg IV every 2 weeks (Q2W). Results: Overall, a total of 58 patients were treated with SHR-1210 at 3 dose levels and schedules: 60 mg Q2W (12 patients); 200 mg Q2W (34 patients), and 400 mg Q2W (12 patients). 49/58 patients received > 2 cycles (each cycle was 28 days) while 36/58 patients were receiving ongoing treatment at the time of abstract preparation. No dose-limiting toxicity (DLT) was observed. The most common adverse events (AEs) related to SHR-1210 included: reactive capillary hemangiomas (79.3%), hypothyroidism (29.3%), pruritus (19.0%), elevated transaminase (13.8%), increased bilirubin (12.1%), fatigue (12.1%), fever (10.3%), and diarrhea (10.3%). Of the 46 cases of hemangiomas, only 5 patients were with grade 2, others were evaluated as grade 1. Of the 17 cases of hypothyroidism were asymptomatic and none exceeded grade 2 severity. Serious AEs suspected to be related to SHR-1210 included one grade 3 acute exacerbation of chronic obstructive pulmonary disease, one grade 3 elevated cardiac troponin I, one grade 4 thrombocytopenia and one grade 4 neutropenia. Overall, the objective response rate as assessed by central review was 31.0%, with a disease control rate of 46.5%. No patients achieved complete response. Eighteen patients had partial response, including 10 esophageal squamous cell carcinoma patients (10/29), three gastric cancer patients (3/8), one lung cancer patient (1/3), one nasopharynx cancer patient (1/3), one hepatocellular carcinoma patient (1/3), one colorectal carcinoma patient (1/3), and one bladder cancer patient (1/1). Conclusions: SHR-1210 was well-tolerated with encouraging antitumor activity and a safety profile. Clinical trial information: NCT02742935.
Effect of GPC1 on epithelial-to-mesenchymal transition and stemness and interaction with ITGB1 in gastric cancer.
Authors: Wang Shiqing , Wu Zhenzhen , Zhou Minyu , Liao Wangjun 
Published: September 2018

e15580 Background: Gastric cancer is the fourth frequently diagnosed cancer worldwide and tumor metastasis plays an important role in its poor prognosis. EMT, which occurs during embryonic development and carcinoma progression, contributes to metastasis and regulates stemness. GPC1, a member of the heparan sulfate proteoglycans family, is overexpressed in many types of cancer, and associates with metastasis and tumor progression. However, it is unknown that the functions of GPC1 and its underlying mechanism in gastric cancer. Methods: Immunohistochemistry analysis was performed in 245 GC tissues to explore the relationship between GPC1 and tumor metastasis. Transwell migration and wound-healing assay were conducted to evaluate the effects of GPC1 on migration and invasiveness. Epithelial marker and mesenchymal markers expression in GC cells were detected by Western blot and immunofluorescence. GPC1 expression induced by TGF-β was detected by Western Blot. After GPC1 was knock downed, the metastatic effect and EMT markers induced by TGF-β were detected. Co-Immunoprecipitation was used to detect the interaction between ITGB1 and GPC1. Results: The expression of GPC1 was higher in GC tissues than in adjacent normal tissues and associated with poor prognosis. Knocking down GPC1 suppressed EMT and stemness which reduced metastasis in vivo and vitro by inhibiting Erk1/2 MAPK and FAK/Akt pathways. TGF-β stimulation significantly upregulated the expression of GPC1 whereas knocking down of GPC1 reversed TGF-β-mediated EMT and stemness. Moreover, we found that knocking down GPC1 could downregulate ITGB1 which was known to promote EMT in gastric cancer. Overexpression of ITGB1 counteracted the influence of knocking down GPC1 on EMT and stemness. Furthermore, GPC1 formed a complex with ITGB1, which indicated that the ability of GPC1 to stimulate EMT is ITGB1-dependent. Conclusions: We conclude that GPC1, through its interaction with ITGB1, plays an important role in regulating TGF-β-mediated EMT and stemness, and could be a potential future therapeutic target to prevent progression of gastric cancer.
A situation where hepatocellular carcinoma (HCC) may be more common in women than men: Clinical and genetic patterns of non risk-factored HCC.
Authors: El Dika Imane Hassan , Harding James J. , Capanu Marinela , Berger Michael F. , Rebibo Dafna , Rusek Matthew , Chou Joanne F. , O'Reilly Eileen Mary , Saltz Leonard , Abou-Alfa Ghassan K. 
Published: September 2018

e15614 Background: Men are classically diagnosed with HCC three times more frequently than women. The gender difference persists after adjusting for confounding risk factors of viral hepatitis and alcoholic cirrhosis, presumably due to protective role of estrogens in women. In rare and unclear circumstances, HCC can arise in patients with no identified risk factor. Methods: Archival FFPE samples from patients with HCC and no underlying liver disease who consented to an IRB-approved protocol from 2014 onward were analyzed using the MSK-IMPACT platform, a hybridization capture based next generation sequencing assay for targeted deep sequencing of all exons and selected introns of > 400 key cancer genes. Tumor and matched normal libraries were sequenced on an Illumina HiSeq 2500. Sequencing output was processed using a custom analysis pipeline. Demographic and treatment data was prospectively collected. Fisher’s exact tests were performed to look for associations between clinical characteristics and genetic alterations. Results: 16 patients were identified with 12 (75%) women affected versus 4 men only. Median age at diagnosis was 64 years. 5 (21%) patients had concomitant other malignancy, being melanoma, lymphoma, mesothelioma, rectal and prostate adenocarcinoma. 75% of patients underwent upfront surgery while only 12% presented with metastatic disease. Median number of genetic mutations was 4. Genetic sequencing did not reveal a specific molecular signature in this subgroup of patients; TERT and CTNNB1 were the most commonly mutated genes, found in 37% of cases. Median follow-up was 20 months and all patients were alive at last follow-up. Conclusions: In contrast to HCC in the general population, we found that HCC in the absence of risk factors is diagnosed more commonly in women than men in this small cohort. Patients in this cohort appear to live longer which can be attributed to normal underlying liver function or different disease biology. The pattern and number of genetic mutations reported herein are not different from those previously reported in risk-factored HCC. The study of a larger cohort of this non-previously defined non-risk factored HCC is warranted.
Benefit of second-line chemotherapy for advanced biliary tract cancer.
Authors: Moik Florian , Riedl Jakob M. , Winder Thomas , Bezan Angelika , Rossmann Christopher , Szkandera Joanna , Kasparek Anne-Katrin , Schaberl-Moser Renate , Pichler Martin , Stoger Herbert , Stotz Michael , Gerger Armin , Posch Florian 
Published: September 2018

e15621 Background: Second-line chemotherapy (2LCTX) is increasingly applied in patients (pts) with advanced biliary tract cancer (aBTC), although no randomized trial has so far demonstrated the benefit of this intervention over best supportive care (BSC) alone. In the absence of randomized data, we thus conducted a comparative effectiveness analysis of survival outcomes in aBTC pts treated with BSC±2LCTX. Methods: In this single-center cohort study, we retrospectively included 80 pts with metastatic, recurrent, or inoperable aBTC who completed 1st-line CTX at our department between 2003 and 2016. Thirty-eight of these pts (48%) received 2LCTX+BSC (Fluoropyrimidine (FP) mono: n = 26 (68%), FP-based combination CTX: n = 9 (24%), Others: n = 3 (8%)). Primary endpoint was 18-month overall survival (OS). An inverse-probability-of-treatment-weighted analysis (IPTW) was implemented to rigorously account for imbalances in prognostic variables between the two study groups. Results: During a median follow-up of 14.8 months, we observed 49 deaths. Six-month, 12-month, and 18-month OS estimates were 77%, 53% and 23% in the BSC+2LCTX group, and 29%, 21%, and 14% in patients in the BSC group, for a univariable hazard ratio (HR) for OS of 0.36 (95%CI: 0.20-0.64, p = 0.001). However, pts receiving 2LCTX+BSC had a significantly higher prevalence of favorable prognostic variables, such as a higher Karnofsky Index (p = 0.0001), lower serum bilirubin (p = 0.03), higher hemoglobin (p = 0.002), and higher serum albumin (p = 0.0007). After careful adjustment for these imbalances using IPTW, 2LCTX+BSC was not associated with an OS benefit over BSC alone (Adjusted HR = 0.62, 95%CI: 0.30-1.29, p = 0.201). In IPTW analysis, 6-, 12-, and 18-month OS were 51%, 33% and 14% in the BSC+2LCTX group, and 35%, 29%, and 19% in patients in the BSC group. The beneficial association of 2LCTX with OS was highly time-dependent, with IPTW HRs of 0.07 (p = 0.002), 0.42 (p = 0.05), and 0.53 (p = 0.11) after 3, 6, and 12 months, respectively. Conclusions: Within the limitations of a non-randomized study, our data support the concept that 2LCTX is associated with a short-term OS benefit in pts with aBTC.
Immune cell surface proteins from tumor samples to predict patient clinical outcome.
Authors: Desai Jasmin Radhika , He Aiwu Ruth , Gusev Yuriy , Bhuvaneshwar Krithika , Smith Coleman , Kroemer Alexander H , Prins Petra 
Published: September 2018

e15630 Background: The incidence and mortality of Hepatocellular carcinoma (HCC) are rapidly increasing in the US. Treatments for advanced HCC are limited despite best efforts to develop therapeutics that target the deregulated pathways of HCC. Recent studies reveal a direct causal relationship between cancer and immune dysfunction, whereby tumor cells and their microenvironment can evade immune attack by exploiting various immunoregulatory mechanisms in a process termed “cancer immune editing”. The objective is to determine the relationship between immune cell surface protein transcripts from tumor samples and the clinical outcome of pts by performing exploratory analyses of liver cancer data from the cancer genome atlas (TCGA). Methods: We analyzed RNAseq data from a cohort of 75 HCC samples in the TCGA collection. We explored the association of expression of a group of specific markers for infiltrating lymphocytes (several subtypes) with overall survival (OS) and these results were confirmed by IHC analysis of the same cell subtypes in HCC samples from patients at GUH. Results: Among the 75 HCC cases analyzed, 25 pts had Hepatitis C (HCV), 25 had Hepatitis B (HBV), and 25 had HCV and HBV co-infection. Fourteen of the 75 cases were found to express the CD8B isoform. The LOG RANK survival test showed a significant association between CD8B levels and OS (ChiSq = 5.2, 1df; p = 0.0222), as did the Cox proportional hazard model for survival. The latter test showed that pts with HCC that did not express CD8B were at a higher risk of death compared with those who had CD8B-expressing HCC. Additional immune cell subtype specific transcripts are being tested. Based on analysis of differentially expressed gene differences between immune cell subtype ‘low’ vs. ‘high’ groups, pathways highly relevant to lymphocyte signaling and immune response and infiltration were identified. Thus, 5 tumor-infiltrating immune cell subtypes were found to have wide variability among patients. Using IHC, these cell subtypes were assessed in HCC samples from patients and correlated to clinical outcome. Conclusions: Immune cell specific transcripts in tumor samples may serve as a predictor of response to treatments that target immune evasion in cancer patients.
Guidelines for management of urgent symptoms in cholangiocarcinoma (CC) patients (pts) with biliary stents or catheters using the modified RAND/UCLA Delphi process.
Authors: Iyer Renuka V. , Acquisto Susan G. , Bridgewater John A. , Choti Michael A. , Hong Theodore S. , Kis Bela , Mead Peter A , Roberts Lewis R. , Roberts Rebecca , Parikh Neehar D. , Sicklick Jason K. , Siegel Richard S. , Whisenant Jonathan R. , Cherepanov Dasha , Broder Michael , Valle Juan W. 
Published: September 2018

e15641 Background: CC pts with biliary stents or catheters are prone to have obstruction/infection and studies show 20-40% present with fever/or jaundice requiring urgent treatment for which there is no uniform guideline. We aimed to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: We recruited 13 physician experts from relevant specialty, geography, and practice settings. Patient scenarios were developed and panelists rated the therapies before and after a face-to-face discussion. The appropriateness of various therapies was rated on a 1-9 scale and classified as appropriate, inappropriate, or uncertain. Scenarios with > 2 ratings of 1-3 (inappropriate) and > 2 ratings of 7-9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions (92%) and the UK (8%); had practiced for a mean 16.5 years (4-33 years). Panelists rated 480 scenarios before the meeting, but re-rated only 288 clinical scenarios as they felt that ongoing treatment with chemotherapy did not influence decision-making. Disagreement decreased from 37.5% before the meeting to 10.4% after. Consensus statements are summarized in the table below. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in urgent management of ascending cholangitis in pts with CC. (Support: The Cholangiocarcinoma Foundation). [Table: see text]
Clinical and epidemiological features in 495 gastroenteropancreatic neuroendocrine patients in Mexico.
Authors: Medrano Guzman Rafael 
Published: September 2018

e15687 Background: Data, incidence and/or prevalence about gastroenteropancreatic neuroendocrine tumors remains unknown in Mexico. Also there is no evidence about any Mexican multicenter study reporting information such as clinical presentation, diagnostic approach and treatment. The biggest problem is the lack of clinical and therapeutic management results so physicians can validate the proper patient protocols. Methods: To know the clinical, epidemiological and therapeutic characteristics of NET-GEP patients treated at the 5 biggest Concentration Mexican Medical Institutions.This paper was developed with the support of 5 Public Medical Institutions: Mexican Social Security Institute (IMSS), Institute for Social Security and Services for State Workers (ISSSTE), Secretary of the Mexican Navy, Petroleos Mexicanos (PEMEX), Ministry of Public Health 495 Patients from 6 hospitals where included: Oncology Hospital, CMN XXI Century, Hospital No. 25 25, Monterrey IMSS, National Cancer Institute (INCAN), National Medical Center November 20, Naval General Hospital of High Specialty and Private Institutions. This was a observational and retrospective academic paper . Results: :Of 495 patients, 59.7% (296) were women and 40.32% (200) were men, 26% of them had around 50 years old. Diagnosis symptoms included: abdominal pain 47.27% (234), gastrointestinal bleeding 18.58% (92) no-predominant symptoms 28.88% (143). Around 32.25% (160) had Carcinoid syndrome and 67.74% (336) were nonfunctioning. The predominant location was pancreas 33.27% (165) and stomach 28.02% (139). 36% resulted circumscribed neoplasia (179), features polypoid 26% (129) and infiltrative 15% (73). The size was > 2cm in 49% (242) > 1-2cm: 36% (180) 0.5 to 1 cm 9% (45) < 0.5 cm 6% (29). Grade: GI 64% (316), GII 13% (66), GIII 23% (114). Metastasis positive ganglioanres (6%) (31), negative (94%) (465). Only seven cases extra nodal metastases (liver (3), lung (2), spleen (2)) Conclusions:This is the first multi-center study in Mexico. Which reflects the clinical characteristics of the NET_GET. The results differ in their epidemiology from that reported in other countries. However, the clinical and therapeutic results are very similar.