bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma membrane localization of human equilibrative nucleoside transporter 1 (hENT-1) to predict better outcome of adjuvant gemcitabine in cholangiocarcinoma (CC) patients.
Authors: Brandi Giovanni , Tavolari Simona , Vasuri Francesco , Farioli Andrea , Deserti Marzia , Frega Giorgio , Corbelli Jodi , Barbera Maria aurelia , Pantaleo Maria A. , Di Girolamo Stefania , Biasco Guido 
Published: March 2020

e15003 Background: The role of adjuvant chemotherapy in CC is controversial and, to date, no standard treatment has been established in this setting. Some institutions offer gemcitabine (GEM) as adjuvant strategy to radically resected CC patients. The efficient uptake of this drug into cells requires the expression and plasma membrane localization of hENT-1. A recent study showed that a high hENT-1 expression closely associated with better survivals in macroscopically (R0 + R1) resected CC patients treated with adjuvant GEM plus S-1. In the present study, we analyzed the relationship between hENT-1 expression/localization and disease free survival (DFS) in CC patients undergone surgery and treated with adjuvant GEM. Methods: A total of 71 CC patients (44 intra-hepatic and 27 extra-hepatic) operated between 2002 and 2011 (46 R0 and 25 R1) and treated with adjuvant GEM (1000 mg/m2, 1-8-15/21 days planned for 6 months) in our institution were enrolled and retrospectively analyzed for hENT-1 expression/localization by immunohistochemistry. Main outcome measure was DFS. Hazard ratios (HR) of relapse and associated 95% confidence intervals (95% CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score (estimated from baseline covariates). Results: 26/71 patients (36.6%) showed a high hENT-1 plasma membrane expression. During a median follow-up of 18.1 months (IQR 9.1–36.2) 49 relapses were observed. Patients with a high expression of hENT-1 showed a reduced risk of relapse (HR 0.50, 95%CI 0.26–0.99, p=0.047). Noteworthy, the effect of hENT-1 appeared to increase across tertiles of duration of gemcitabine-based adjuvant chemotherapy (lower tertile, ≤102 days: HR 0.87, 95%CI 0.30–2.53; middle tertile, 103–170 days: HR 0.68, 95%CI 0.22–2.06; higher tertile, ≥171 days: 0.20, 95%CI 0.04–0.94). Conclusions: High plasma membrane hENT-1 expression was associated with a longer DFS among CC patients. The interaction between hENT-1 expression and duration of chemotherapy deserves further investigations, as it could be useful to tailor optimal GEM-based adjuvant chemotherapies.
Diagnostic discrepancies between second-opinion and referring pathology reports of neuroendocrine tumors.
Authors: Lin Hillary , Longacre Teri A. , Khandelwal Vilay H. , Balise Raymond R. , Kunz Pamela L. 
Published: March 2020

e15011 Background: The nomenclature and histologic classification schemes for neuroendocrine tumors (NETs) have historically been heterogeneous and inconsistent. However, clinicians require specific descriptors to determine treatment plans for patients. In 2010, Klimstra, et al. published a set of NET pathology reporting guidelines. Using these guidelines, we undertook a systematic evaluation of discrepancies between referring versus Stanford second-opinion NET pathology reports. Methods: We developed a cohort ofall NET cases seen at Stanford University Hospital between April 1998 and December 2012 with available Stanford and referring pathology reports for the same specimen to identify the discrepancies between their clinical diagnoses. Results: Of 170 cases, histological diagnoses were discrepant in 79% of the reports; 89 (66%) of which were clinically insignificant, and 46 (34%) clinically significant. Stanford used 14 unique terms for histological description, and referring institutions used 49 unique terms. Grade, mitotic index (MI), and Ki67 were among the variables examined; they were not reported (NR) from the majority of cases in one or both reports, yet more likely to be included in the Stanford report. Grade was NR in one or both reports in 152 cases (89%); of the 18 cases reporting grade in both reports, 3 (2%) were discrepant. MI was NR in one or both reports in 128 cases (75%); of the 42 cases reporting MI in both reports, 27 (16%) were discrepant. Ki67 was NR in one or both reports in 153 cases (90%); of the 17 cases reporting Ki67 in both reports, 12 (7%) were discrepant. Reporting was found to improve over time for these variables (five-year blocks from 1998-2012). There was a trend towards improved reporting from academic hospitals (vs. non-academic hospitals) and by Stanford NET pathology experts (vs. general pathologists). Conclusions: Clinically relevant differences were frequently found between Stanford and referring pathology reports for NETs. Future studies of NET pathology discrepancies are warranted to allow additional time for adoption of the 2010 guidelines.
Phase I/II study of PCI-27483, a coagulation factor VIIa (FVIIa) inhibitor, in combination with gemcitabine in patients with advanced pancreatic cancer.
Authors: Mahesh Sameer A. , Gabrail Nashat Y. , Gandhi Jitendra G. , Khorana Alok A. , Manges Robert , Shah Satish , Thomas Gary W. , Hamdy Ahmed M. , Stevens-Brogan Michelle , Zhou Cathy , Elias Laurence , Loury David , Ramanathan Ramesh K. 
Published: March 2020

e15014 Background: Tissue factor (TF) up-regulation is associated with increased tumor invasiveness and progression, worsened prognosis and increased thromboembolism (VTE). Activation of protease activated receptors by TF:FVIIa complex leads to increases in IL-8, VEGF and other invasiveness promoting factors. PCI-27483 (P), a selective FVIIa inhibitor, reduced pancreatic adenocarcinoma (PCa) xenograft growth in mice at doses producing 2.5 - 3.0 x PT changes. Methods: Escalating doses of P combined with gemcitabine (G) targeting peak (2 hr post) INR = 3.0 was studied in Phase I preceding randomization to G+P at the determined dose vs. G alone in Phase II. Eligible patients (pts) had measurable locally advanced or metastatic PCa, ECOG PS 0-1, and normal PT/aPTT, and no history of VTE. G was given IV at 1 G/m2 q wk X3 every 4 wks, and P was self-administered SC bid continuously. Tumor evaluation including spiral CTs were performed at baseline and q 8 wks. Results: In phase I, 8 pts were enrolled and the targeted INR was attained at 1.2 mg/kg. In phase II, 34 patients were randomized, 16 to G and 18 to G+P. The randomized arms were well balanced; overall 88% had metastatic disease; most had liver involvement. Among pts randomized to P+G, mean ± SD 2-hr post injection INR was 3.1 ± 1.2 on D8 and 2.8 ± 1.0 on D22 (n=13). P dosing was continued for up to 96 wks; mean ± SD: 17 ± 24 wks. Dose reduction to maintain target INR was required for 6 pts. Overall tolerability and safety of G+P was similar to that of G, with a higher incidence of mostly low grade bleeding events and decreased Hgb. Efficacy measures of G vs G+P pts were not significantly different (Table). Conclusions: PCI-27483 +G was well tolerated at doses of P up to 1.5 mg/kg bid. The safety profile of the combination was consistent with that expected of each agent. While the clinical endpoints were not achieved in pancreatic cancer, the targeted inhibition of the coagulation cascade was achieved. Clinical trial information: NCT01020006. [Table: see text]
Quantitative detection of intraabdominal floating tumor cells and clusters using flowcytometry in patients with peritoneal carcinomatosis.
Authors: Kitayama Joji , Kamei Takao , Emoto Shigenobu , Yamaguchi Hironori , Ishigami Hironori 
Published: March 2020

e15027 Background: Peritoneal metastasis (P) is the most life-threatening types of metastasis in patients with gastrointestinal cancer. Although the presence of tumor cells in peritoneal cavity is evaluated with microscopic observation by pathologists (Cy) or detection of mRNA of tumor specific molecules, no reliable method is available to quantify the accurate volume of tumor cells. Methods: Acsites or peritoneal lavages were recovered from 72 patients who underwent abdominal surgery for gastrointestinal cancer. In patients who received intraperitoneal (IP) chemotherapy for peritoneal metastasis, 40 samples were obtained from subcutaneous intraperitoneal access port during the course of chemotherapy. In those 112 samples, cells were recovered by centrifugation, fixed and immunostained with mAbs to CD45 and to CD326 (EpCAM). Using FACS analysis, CD326(+)CD45(-) and CD45(+)CD326(-) cells were determined as tumor cells (T) and leukocytes (L), respectively, and T/L ratio was calculated. Results: In 72 patients with surgery, Median (M) of T/L ratio of the P(+) patients was 15.3% (0%-751.3%), which was significantly higher than P(-) patients (M=0%, 0%-2.1%, p<0.001). In P1 patients, 50 samples which was determined as positive cytology (Cy+) showed higher T/L ratio as compared with 33 samples with Cy (-) (M=23.0%, 0.3%-751.3% vs M=0.53%, 0%-3.5%, p<0.0001). In 17 patients who underwent IP chemotherapy, T/L ratio was markedly decreased after chemotherapy (M=75%, 0.2%-339.0% vs M=0.16%, 0%-35.0%, p<0.0001) and the response was more sensitive than Cy. Moreover, the MST of the 21 P1 patients who showed T/L ratio less than 10% at initial examination was 459 days, while MST of 8 P1 patients whose CT/L ratio was more than 10% was 188 day (p<0.0012). Conclusions: T/L ratio measured with flowcytometry well reflects the total volume of intraperitoneal tumor cells and could be a reliable biomarker to predict the prognosis as well as effectiveness of IP chemotherapy in P1 patients in gastrointestinal cancer.
The management of dysphagia in esophageal adenocarcinoma patients undergoing neoadjuvant chemotherapy: Can invasive tube feeding be avoided?
Authors: Cools-Lartigue Jonathan , Jones Daniel , Zourikian Taline , Rousseau Mathieu , Spicer Jonathan , Eckert Eleanor , Alcindor Thierry , Ferri Lorenzo 
Published: March 2020

e15034 Background: Neoadjuvant chemotherapy is an accepted standard for locally advanced esophago-gastric adenocarcinoma. However the dysphagia frequently associated with this condition may interfere with patient tolerance of neoadjuvant chemotherapy. Surgical or endoscopic invasive tube feeding (ITF), including stents, is a commonly employed strategy to maintain nutritional support however it can cause significant morbidity in its own right. We sought to determine if an approach of careful dietary counseling and fast-tracked neoadjuvant chemotherapy can obviate the need for ITF. Methods: Pts undergoing neoadjuvant chemotherapy (DCF or ECF Q3 weeks x3 or FLOT Q2weeks x4) for locally advanced (cT3 and/or N+) esophageal or EGJ adenocarcinoma at a single institution from 3/07-9/12 were identified from a prospective database. All received dietary counseling and were closely monitored for signs/ symptoms of malnutrition with serial (baseline/pre-surgery) Body Mass Index (BMI), albumin, dysphagia scores (DS: 0 best - 4 worse), and quality of life (FACT-E). We assessed the response of dysphagia and nutritional status to neoadjuvant treatment and the need for ITF. Data presented as median (Interquartile Range) or median (±SD), paired t-test or Wilcoxon signed ranks test determined significance (*p=0.05). Results: Of 130 patients undergoing neoadjuvant chemotherapy 78 had dysphagia scores of 2 or greater, most of whom received DCF (91%). Overall the dysphagia improved in 75/78 (96%) from a DS of 3 (2-4) to 0 (0-1)*. This was associated with an increase in FACT-E QoL scores (117±23 to 140±20)*. Weight (Kg)(70±22:69±24), BMI (24.5±8 to 23.9±7), and Albumin (40±5 to 37±4) were maintained. Only one patient required a stent, and none a jejunostomy, or gastrostomy. Conclusions: Appropriately timed neoadjuvant chemotherapy with a highly effective regimen rapidly restores normal swallowing, maintains nutritional status, and obviates the need for stenting or invasive tube feeding in patients with significant dysphagia from esophageal adenocarcinoma.
Oxaliplatin, irinotecan, bevacizumab followed by docetaxel, bevacizumab in inoperable gastric cancer: Final efficacy results of a multicenter phase II trial (AGMT Gastric-3) of the arbeitsgemeinschaft Medikamentöse tumortherapie (AGMT).
Authors: Woell Ewald , Keil Felix , Thaler Josef , Gruenberger Birgit , Hejna Michael , Eisterer Wolfgang , Fridrik Michael A. , Romeder Franz , Greil Richard 
Published: March 2020

e15041 Background: We could show efficacy of oxaliplatin and irinotecan as well as oxaliplatin, irinotecan and cetuximab in previous trials.Time to progression however was short suggesting acquired chemotherapy resistance.To address this problem sequential chemotherapy combined with bevacizumab is investigated in the presented Gastric-3 trial. Methods: Oxaliplatin 85 mg/m2 and irinotecan 125 mg/m2 are administered biweekly (q2w) for the first three months followed by docetaxel 50mg/m2 q2w for subsequent three months. Chemotherapy is combined with bevacizumab 5 mg/kg q2w which is administered until progression. Primary endpoint is response rate. 40 patients (pts.) with histological proven unresectable and/or metastatic gastric adenocarcinoma treated in a first-line setting are evaluated. Median age: 62.5 years PS 0: 26 pts., PS 1: 12 pts., missing: 2 pts.,single metastatic site: 25 pts., multiple metastases: 13 pts., missing: 2. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 and included diarrhea (72.5%), nausea (65%), emesis (50%), abdominal pain (50%), fatigue (47.5%), polyneuropathy (40%), neutropenia (25%), hypokalemia (22.5%), hypertension (22.5%). Grade 3 and 4 toxicities included neutropenia (25%), diarrhea (12.5%), ileus/subileus (10%), hypokalemia (7.5%), leucopenia (7.5%), anemia (5%), meningiosis carcinomatosa (5%). Objective response rate after 3 cycles was available in 31 patients: CR 1/31 (3.2%), PR 48.4%, SD 35.5%, PD 12.9%. After 6 cycles there were 14 evaluable patients with CR 2/14 (14.3%), PR 42.9%, SD 35.7% and PD 7.1%. Median progression free survival was 32 weeks, median overall survival was53 weeks. Progression rate or death was 34/40 (85%), mortality 29/40 (72.5%). Maintenance therapy was given in 12/40 pts. (30%). Median time on maintenance therapy was 17 weeks, range (2 – 77). Conclusions: The combination of oxaliplatin and irinotecan with bevacizumab followed by docetaxel with bevacizumab is feasible and active in advanced gastric cancer. Clinical trial information: 2008-006128-79.
Correlation of prognosis with the gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma.
Authors: Wang Yijun , Shan Shigang , Gao Yingtang , Zhang Qin , Wang Fengmei , Jing Xiang , Du Zhi 
Published: March 2020

e15050 Background: Serum golgi protein73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and it correlation with clinicopathologic parameters. Methods: Tissue GP73 (tGP73) levels were detected in specimens of group A (n=186) including HCC (n=62), peritumoral tissue (PTL) (n=43), high/low-grade hepatic atypical hyperplasia (AH) (n=32/2), chronic hepatitis B (CHB) (n=42) and normal controls (NC) (n=5) by immunohistochemistry, and GP73 expression in group B (n=159) and group C (n=16) were detected by RT-PCR and Western blot respectively. sGP73 levels were detected in subjects of group D (n=287) by ELISA. Results: GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P<0.05), while sGP73 in HCC group was lower than in liver cirrhosis (LC) group (P<0.001). Both tGP73 and sGP73 levels were negatively associated with tumor size and TNM stage, and tGP73 levels were positively associated with tumor differentiation. The high-tGP73 group showed significantly better overall and disease-free survival than low-tGP73 group (P=0.008, P=0.018). Multivariate analysis revealed that the tGP73 level was an independent prognostic factor for HCC, but not sGP73. Conclusions: GP73 increases gradually in the progression ofbenign liver diseases to precancerous lesions and HCC. This expression pattern suggests the regulatory mechanism of GP73 is related to the progression of chronic liver diseases. Furthermore, a high level of tGP73 is a favorable prognostic factor for HCC.
An assessment of the impact of geographic variation on resection rates and survival for early-stage pancreatic adenocarcinoma.
Authors: McDowell Bradley D. , Smith Brian J. , Button Anna M , Howe James R. , Chrischilles Elizabeth A. , Mezhir James J. 
Published: March 2020

e15052 Background: Pancreatic resection is the only known curative option for pancreatic adenocarcinoma. Resection has been previously reported to be underutilized in patients with early stage disease. To develop a better understanding of this issue and control for treatment selection factors, we examined the relationship between geographic area resection rates and survival in patients with stage I/II pancreatic cancer. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) data for patients with stage I/II cancer of the pancreatic head diagnosed from 2004-2009. We excluded patients with less than 3mo survival. Resection rates were calculated within Health Service Areas (HSAs) across all 18 SEER regions. Resection rate was defined as the number of patients who had an operation divided by the total number diagnosed with early stage pancreatic cancer. Multivariate Cox regression was used to estimate the overall survival effect of HSA rates while controlling for age, gender, marital status, poverty level, education, and AJCC stage. Results: 8,323 patients with stage I (n=1,454) and stage II (n=6,869) disease were analyzed. Pancreatectomy was performed in 476 patients (32.7%) with stage I disease and 3,846 (56.0%) with stage II disease. HSA resection rates were arranged into five groups (quintiles) which ranged from 42.7 to 65.7% (Table). Across the quintiles, median overall survival increased from 11 to 14 months, suggesting a positive association with resection rate. Multivariate analysis revealed that for every 10.00% increase in resection rate, the risk of overall death decreased by 5.26% (p<0.001). Conclusions: Patients with early stage pancreatic cancer who live in areas with higher resection rates have longer average survival times. Because geography should not influence treatment response, we conclude that efforts to raise resection rates should increase survival times in patients for whom there is uncertainty about the risk/benefits of resection. [Table: see text]
Phase II trial of nemorubicin hydrochloride (N) in combination with cisplatin (cDDP) administered by intra-hepatic artery (IHA) in patients (pts) with hepatocellular carcinoma (HCC): Final results.
Authors: Izzo Francesco , Vogl Thomas J. , Gadaleta-Caldarola Gennaro , Middleton Mark R. , Valle Juan W. , Hammerstingl Renate , Gadaleta Cosmo D. , Martignoni Marcella , Petroccione Anna , Mariani Mariangela , Davite Cristina , Fiore Francesco 
Published: March 2020

e15061 Background: N is a novel DNA-intercalator, mainly metabolized in liver by CYP3A4 enzyme and showing synergic antitumor activity with cDDP. The objective of this study was to evaluate the efficacy and toxicity of N administered by IHA in combination with cDDP to unresectable HCC pts. Methods: The study was in two HCC pt populations: advanced risk (ARP) (CLIP 2, bilirubin ≤ 2.5 mg/dL, portal vein thrombosis [PVT] admitted) and intermediate risk (IRP) (CLIP 0-1, bilirubin ≤ 1.5 x ULN, no PVT). Treatment was repeated every 4-6 wks for a maximum of 6 courses, if acceptable toxicity and no disease progression occurred. A single-arm, Simon’s Minimax two-stage design was adopted to evaluate the primary endpoint of tumour response (WHO criteria, critical numbers of responses to reject H0were ≥ 6/29 evaluable pts and ≥ 11/33 evaluable pts in ARP and IRP, respectively). Results: Thirty-seven ARP pts (27 evaluable) and 42 IRP pts (33 evaluable) were enrolled. The median number of cycles was 3 in both ARP (range 1-13; dose 400 mcg/m2 nemorubicin and 60 mg/m2 cDDP) and in IRP (range 1-6; dose 600 mcg/m2 nemorubicin and 60 mg/m2 cDDP). The trial was successful in ARP with 8 successes/27 evaluable pts (RR 30%): 7 partial responses (PR), 1 downstaging and 8 minor responses (MR)/ disease stabilization (SD) > 3 months. The IRP did not meet the efficacy criteria:2 CR, 5 PR and 13 MR/SD > 3 months (7 responses/33 evaluable pts; RR 21%). Overall, the main Grade 3-4 hematological and biochemical toxicities in ARP/IRP were thrombocytopenia (28/58%), neutropenia (26/60%), aspartate aminotransferase (25/31%), alanine aminotransferase (14/23%) and bilirubin increase (17/21%). The most frequent adverse events (any Grade ≥ 20%) were fatigue (38%), nausea (35/29%), and vomiting (24/26%). Conclusions: The trial was successful in ARP but not in IRP; IHA infusion of N with cDDP showed promising activity in both IRP and ARP with a well tolerated regimen. These encouraging results warrant further investigation in HCC, specially in multinodular type. Clinical trial information: 2005-000731-26.
Docetaxel, oxaliplatin, and capecitabine (DOX) combination chemotherapy for metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Di Lauro Luigi , Sergi Domenico , Belli Franca , Fattoruso Silvia Ileana , Arena Maria Grazia , Pizzuti Laura , Vici Patrizia 
Published: March 2020

e15065 Background: So far, the prognosis of advanced gastric cancer is dismal. Combination chemotherapy of docetaxel (D), cisplatin (C) and fluorouracil (F) showed activity in metastatic gastric cancer, but this regimen was complicated by a high incidence of myelotoxicity. We performed a multicenter phase II trial substituting C with oxaliplatin (O) and F with capecitabine (X) in chemotherapy-naive patients (pts) with gastric or GEJ adenocarcinoma. Methods: Pts with measurable distant metastases received D 60 mg/mq iv, O 100 mg/mq iv on day 1 and X 500 mg/mq orally twice daily continuously, with cycles repeated every 3 weeks for a maximum of 8. G-CSF was used only as secondary prophylaxis. The primary endpoint was overall response rate (RR) according to RECIST. Toxicity was reported according to NCI-CTC v 3.0. Optimal Simon's two-stage design was employed with 6/15 responses required in the first stage to allow continuation to 46 pts. Results: 46 pts were enrolled: M/F 28/18; median age 66 years (32-75); median ECOG PS 1 (0-2); primary tumor resected/ unresected 16/30; disease location was gastric in 34 and GEJ in 12 pts; sites of disease were liver in 27, nodes in 25, peritoneum in 20, lung in 8 and bone in 5 pts. At the time of analysis all pts were evaluable for response and toxicity. In 46 pts, 3 CR and 21 PR were observed, for an overall RR of 52.1% (95% CI, 37.7%-66.5%). Responses were obtained in 15/27 pts (55%) with liver metastases. Disease remained stable in 14 pts (30.5 %). Median TTP was 6.8 months and median OS was 12.6 months. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 41%, 4% and 9% of the pts, respectively. Febrile neutropenia was observed in 2 pts (4%). Other grade 3 toxicities included mucositis in 2 pts (4%), vomiting in 3 pts (6.5%) and diarrhea in 2 pt (4%). There were no severe neurotoxicity, nor treatment-related deaths. Conclusions: The DOX combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric or GEJ adenocarcinoma and deserves further evaluation in randomized trials and, hopefully, in neoadjuvant setting.