bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factor of carcinoma of the ampulla of vater after surgery.
Authors: Tomiyasu Shinjiro , Oda Eri , Tanaka Hiroshi , Ishikawa Shinji , Sugita Hiroki , Arita Tetsumasa , Yagi Yasushi , Takamori Hiroshi , Kanemitsu Keiichiro , Hirota Masahiko , Baba Hideo 
Published: February 2017

270 Background: General rules for biliary tract cancer in Japan were revised and Stage of biliary tract cancer was compliant with the seventh UICC. Carcinoma of the Ampulla Vater (CAV) is relatively good prognosis among the biliary tract cancer, such as lymph node metastasis, pancreatic invasion and perineural invasion has been reported to be prognostic factors. We investigated the validity of TNM-Stage by examining the prognostic factors from the outcome of resection experienced. Methods: To evaluate prognostic factors after surgery based on a series of 70 patients of CAV from 1996 to 2014. Twenty-eight patients received pancreatoduodenectomy (PD), 25 patients received pylorus-preserving pancreatoduodenectomy (PPPD) and 17 patients received subtotal stomach-preserving pancreatoduodenectomy (SSPPD). We reviewed and analyzed the clinicopathologic data, surgical outcomes, recurrence and survival. Results: Actuarial disease-specific survival (DSS) was 65 % at five years. In univariate analysis, pancreatic invasion, lymph node metastasis and duodenal invasion are significantly poor prognosis. In multivariate analysis, pancreatic invasion is the only poor prognostic factor (p = 0.0023, hazard ratio (HR) 5.31 [confidence interval (CI) 1.77-18.9 95%]); lymph node metastasis and duodenal invasion are not significantly different (p = 0.0672 and 0.8769, respectively). Also, in the study of relapse risk factors, pancreatic invasion and lymph node metastasis are significantly different. In TNM-Stage II, those of T3N0, 1 are poor prognosis than T1, 2N1 (p = 0.0334). Conclusions: Pancreatic invasion is an independent poor prognostic and recurrence risk factor. The Stage of Japanese Society of Biliary Surgery has reflect prognosis than TNM-Stage in carcinoma of the Ampulla Vater.
Adenosquamous cell carcinoma derived from intraductal papillary mucinous neoplasm of the pancreas confirmed by genetic analysis.
Authors: Karasaki Hidenori , Kono Toru , Ono Yusuke , Maejima Taku , Mizukami Yusuke 
Published: February 2017

275 Background: Adenosquamous cell carcinoma (ASC) is an uncommon histologic variant of pancreatic cancer, representing only 1-4 % of all pancreatic neoplasms. Here we reported the extremely rare case of ASC derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreas with intensive pathological and molecular analysis. Methods: A 72-year-old diabetic male with five-year history of non-alcoholic chronic pancreatitis was admitted to our hospital with complaint of epigastric pain. The patient was diagnosed as pancreatic cancer associated with IPMN and pylorus preserving pancreaticoduodenectomy was performed in April 2012. The resected pancreas was fixed in 10% formaldehyde, and the whole specimen was sliced at a thickness of 5-mm for i) pathological analyses using hematoxylin-eosin (H-E) staining and immunostaining with specific antibodies against MUC-1, -2, -5AC, -6, p63 and CD5/6, and ii) deep sequencing of multiplex PCR amplicons of 50 cancer-associated genes utilizing Ion Torrent PGM platform. DNA was obtained from intraepithelial lesions of IPMN, invasive squamous cell carcinoma (SCC) and adenocarcinoma (AC) after enrichment for neoplastic cellularity, using manual microdissection. Results: Pathological findings showed IPMN extended from main pancreatic duct to branch ducts. The invasive tumor was predominantly consisted of poorly-differentiated SCC and small poorly-differentiated AC was also found in the edge of the SCC. All IPMN area analyzed shared combination of the mutations, KRASG12D and GNASR201C. The identical mutations in KRAS and GNAS as IPMNs were also found in SCC and AC. Conclusions: It generally difficult to fully discriminate IPMN-derived cancer (invasive IPMN) from concomitantly and independently developed de novo pancreatic ductal adenocarcinoma (PDA) originating from the “field defect”. In the current case, although SCC is a rare histotype of IPMNs, we considered that the invasive carcinoma was derived from IPMN based on their mutational profile.
Gene-pair classifier in circulating tumor and invasive cells to predict pharmacological response.
Authors: Sangar Vineet , Earls John C , Yu Kenneth H. 
Published: February 2017

279 Background: Improved diagnostic tools for predicting treatment response and prognosis are needed in pancreatic adenocarcinoma (PDAC), the fourth leading cause of cancer mortality in the U.S. In this study, we explored the diagnostic potential of gene expression signatures from circulating tumorigenic and invasive cells (CTICs). Methods: We recruited 50 PDAC patients to participate in our IRB-approved study. 35 patients were evaluable for response to chemotherapy treatment. 10 mL of peripheral blood was collected from patients with unresectable PDAC prior to initiating chemotherapy and again at disease progression. Clinical data was prospectively collected. Blood was processed for isolation of circulating TP cells (Vita-Cap, Vitatex Inc.), total RNA was extracted and gene-expression analysis was performed (Affymetrix GeneChipHuman Genome U133 Plus 2.0 array). Using time to progression (TTP) as a threshold, twenty-five patients with TTP>120 days were labeled as responders and ten patients with TTP<=120 days were labeled as non-responders. Results: Network analysis of expression profiles revealed that the PTC1 and CDC25 pathways were significantly different in responders and non-responders. Both pathways contribute towards tumorigenesis, and enhance tumor resistance to therapeutic intervention in PDAC. Further investigation into these pathways revealed that the relative expression of ATM and XPO1 was the most accurate classifier (76% accuracy, Specificity = 80% and Sensitivity = 72%). Additionally, 18 out of 20 patients of the patients with ATM < XPO1expression pattern responded to treatment. Mechanistically, this observation suggests that ATM may be counteracting DNA damage inflicted by chemotherapy during G2/M transition of the cell cycle. Conclusions: Computational analysis of gene expression data from CTICs can reliably predict pharmacological response. Pathway analysis identifies gene interaction networks relevant to tumorigenesis and drug response. Data will be updated with longitudinal analysis of treatment response in both responders and non-responders to the treatment.
A high density of tumor infiltrating CD3 and CD8 cells to predict recurrence free survival in patient with hepatocellular carcinoma.
Authors: Gabrielson Andrew , Wu Yunan , Kallakury Bhaskar , Jiang Jiji , Wang Hongkun , Johnson Lynt B. , Island Eddie , Fishbein Thomas , Satoskar Rohits , Jha Reena , Kachhela Jaydeep , Feng Perry , Zhang Tiger , Tesfaye Anteneh , Bhuvaneshwar Krithika , Gusev Yuriy , Prins Petra , Marshall John , Atkins Michael B. , He Aiwu Ruth 
Published: February 2017

280 Background: The ability to define risk of hepatocellular carcinoma (HCC) recurrence after resection could improve the clinical management of patients. The pathological factors currently indicative of tumor invasiveness, such as vascular invasion, elevated AFP and advanced pTNM stage, are the established risk factors for recurrence. It has been suggested that immune cells that infiltrate a tumor are a prognostic factor in predicting patient outcome. In this study, the prognostic significance of tumor immune infiltration, as defined by the Immunoscore methodology, was assessed in patients with HCC. Methods: The influence of immune infiltration on clinical outcome was evaluated in patients who had undergone resection of HCC. The density of intratumoral immune infiltrates were measured in the center of the tumor (CT) and in the invasive margin (IM) of 45 stage I to IV HCC tissue specimens from a single cohort. The density of total (CD3+) and cytotoxic (CD8+) T lymphocytes in the CT and IM were obtained by immunohistochemistry and quantified using a Nuance FX Multiplex Biomarker Imaging system in tandem with ImageJ image processing software. Immune cell density in the CT and IM was converted to a binary score (0 as Low, 1 as High), with a cutoff threshold determined by the median density of CD3+ and CD8+ cells (273 cells/mm² and 217.5 cells/mm², respectively). The Immunoscore values were correlated with tumor recurrence and recurrence-free survival. Results: High densities of both CD3+ and CD8+ T lymphocytes in the CT and IM, along with a corresponding Immunoscore of 3+ (on a scale from 0 to 4), were significantly correlated with a low rate of recurrence (p-value = 0.0004). High densities of CD3+ lymphocytes alone were correlated with a prolonged recurrence-free survival (p-value = 0.0005). High densities of CD8+ lymphocytes alone were also correlated with a prolonged recurrence-free survival (p-value = 0.0031). Conclusions: The Immunoscore is a useful prognostic marker in patients with HCC who have received primary tumor resection. To better characterize the immune landscape of HCC tumors, the correlation between the Immunoscore and additional immune biomarkers are being evaluated.
A phase II, open-label, randomized clinical trial of panitumumab plus gemcitabine and oxaliplatin (GEMOX) versus GEMOX alone as first-line treatment in advanced biliary tract cancer: The Vecti-BIL study.
Authors: Leone Francesco , Marino Donatella , Filippi Roberto , Cereda Stefano , Belli Carmen , Spadi Rosella , Nasti Guglielmo , Montano Massimo , Amatu Alessio , Aprile Giuseppe , Cagnazzo Celeste , Fasola Gianpiero , Siena Salvatore , Ciuffreda Libero , Reni Michele , Aglietta Massimo 
Published: February 2017

281 Background: Biliary tract cancer (BTC) is a rare and lethal disease with very few therapeutic options. Preclinical data suggest that Epithelial Growth Factor Receptor (EGFR) pathway activation could be involved in BTC pathogenesis, envisaging a potential role of anti-EGFR monoclonal antibodies. Methods: Patients (pts) with metastatic or unresectable BTC, harboring wild-type KRAS status, with ECOG performance status 0-2, without prior systemic therapy, were randomized to GEMOX (gemcitabine, 1000 mg/m² and oxaliplatin, 100 mg/m²) therapy with (arm A) or without (arm B) panitumumab (6 mg/kg), q2w for up to 12 cycles. Maintenance therapy with panitumumab alone was allowed in arm A in case of clinical benefit after 12 cycles. The primary endpoint was the progression-free survival (PFS). The target hazard ratio was 0.60 requiring 88 pts for 74 PFS events (80% 1-β power, α = 0.10, log-rank test 1-sided). Secondary endpoints were objective response rate (RR) (RECIST vers.1.1), overall survival (OS), and safety. Results: From 06/2010 to 09/2013, 89 pts were enrolled (median age 64 years; metastatic 78%; gallbladder 32%, extra-hepatic 21%, intra-hepatic 47%). After a median follow-up of 8.6 months (mo), with six pts (two progression-free) in arm A, and eight pts (none progression-free) in arm B still in follow-up, median PFS was 7.7 mo in arm A (95% CI 4.7–10.6) and 5.5 mo (95% CI 3.2–7.8) in arm B (p=0.10). RR was 25.0% in arm A and 18.2% in arm B. No differences in survival were seen, being median OS 9.5 mo (95% CI 5.7-13.3) in arm A and 9.9 mo in arm B (95% CI 5.1-14.6), p= 0.49. The most common all grade toxicities were skin toxicity (71%), nausea (67%), and fatigue (53%) in arm A; nausea (64%), neurotoxicity (57%), and fatigue (52%) in arm B. The most common grade 3 or 4 toxicities were: hepatic toxicity (20%), diarrhea (13%), and nausea (13%) in arm A; cholestasis (14%), dyspnea (9%), and diarrhea (9%) in arm B. Conclusions: Although the results are not fully mature, the combination of GEMOX and panitumumab showed a trend towards better PFS and RR in KRAS wild-type BTC pts as compared to GEMOX alone. No impact on OS seems evident. Clinical trial information: NCT01389414.
Effect of KRAS mutation on long-term outcomes of patients undergoing hepatic resection for colorectal liver metastases.
Authors: Margonis Georgios A , Spolverato Gaya , Kim Yuhree , Karagkounis Georgios , Choti Michael A. , Pawlik Timothy M. 
Published: February 2017

282 Background: The impact of KRAS mutation on overall (OS) and recurrence-free (RFS) survival of patients with colorectal liver metastases (CLM) remains poorly defined. We sought to investigate the prognostic value of KRAS in a large cohort of patients undergoing liver resection for CLM. Methods: Between 2003 and 2013, 334 patients underwent hepatic resection for CLM at Johns Hopkins Hospital and met the inclusion criteria. Somatic mutations at codons 12/13 were evaluated through a sequencing analysis of the tumor samples. Clinicopathological characteristics, perioperative details, and outcomes were stratified by KRAS status (mtKRAS vs. wtKRAS) and analyzed. Results: Among 334 patients undergoing liver resection for CLM, mtKRAS was identified in 115 (34.4%) patients. Median CEA was 7.3 ng/dL; 40.4% of patients had a solitary tumor and median tumor size was 2.5 cm. At a median follow-up of 28.2 months, recurrence was observed in 59 (51.3%) patients with mtKRAS and 117 (53.4%) patients with wtKRAS (P=0.71); there was no difference in the pattern of recurrence (liver: mtKRAS, 39.0% vs. wtKRAS, 52.1%; lung: mtKRAS, 55.6% vs. wtKRAS, 64.3%; both P>0.05). While 5-year log-rank OS was comparable among mtKRAS (41.6%) vs. wtKRAS (48.5%), on multivariable Cox survival analysis mtKRAS was associated with worse OS(HR, 1.65; 95%CI, 1.07-2.54). Moreover, among patients who experienced a recurrence, 5-year OS was worse among those patients who had mtKRAS (mtKRAS, 28.1% vs. wtKRAS, 44.5%; P=0.004). After controlling for tumor factors, as well as receipt of chemotherapy, mtKRAS status remained independently associated with a worse outcome among patients who recurred(HR 2.07, 95% CI 1.31-3.27; P=0.002). Conclusions: mtKRAS was noted in one-third of patients with CLM. While KRAS status did not impact pattern of recurrence, mtKRAS was an independent predictor of worse OS among patients who experienced a recurrence following resection of CLM.
Overall survival and clinical characteristics in BRCA mutation carriers with stage I/II pancreatic cancer (PC).
Authors: Golan Talia , Sella Tal , Javle Milind M. , Borgida Ayelet , O'Reilly Eileen Mary , Kelsen David Paul , Epelbaum Ron , Kindler Hedy Lee , Katz Matthew H. G. , Gallinger Steven 
Published: February 2017

287 Background: BRCA1/2 mutation carriers with PC may have distinct biologic outcomes. We recently described favorable overall survival (OS) in patients with early-stage resected PC. However the prognostic impact of germline (GL) BRCA1/2 mutations in surgically-resected PC cases has not been yet compared with institution-matched controls. Methods: A multi-center, case-control retrospective analysis was performed of patients with surgically-resected, BRCA1/2 mutated PC from years 2001-2012. Non-hereditary PC controls were defined as BRCA negative or absence of a personal and first degree familial history of breast, ovarian or PC. Cases were matched by: age at diagnosis (+/- 5 years), treatment (neoadjuvant vs. adjuvant) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ2and Fisher's exact test and median DFS/OS using Kaplan-Meier method and log-rank testing. Results: 20 patients with GL BRCA1/2 mutation PC were identified and matched (1:2) with 40 non-hereditary controls. Cases were comparable to controls in all tumor and treatment (neoadjuvant vs. adjuvant) related variables except lymphovascular involvement (30.6% vs 64.7%, p= 0.014). However, BRCA cases frequently received neoadjuvant (8/10 vs 6/14)/adjuvant (7/15 vs 3/34) platinum-based treatment. Clinical characteristics of GL BRCA1/2PC cases: BRCA1=3, BRCA2=17. Mean age was 56.7 years (41-78, SD 10.0), 65% (n=13) were female, 55% (n=11) were Jewish, 55% (n=11) had a family history and 95% (n=19) were stage II at resection. We demonstrated no difference in median OS (23.8 vs 25.9 months, p=0.397) and in DFS (13.6 vs 12.6 months, p=0.404) in BRCA1/2 mutation carriers vs controls. BRCA1/2mutation carriers did not experience improved DFS or OS with platinum-based chemotherapy. Conclusions: In this retrospective analysis, the prognosis of surgically-resectable BRCA associated PC is no different than that of sporadic PC from the same institution. The role of DNA damaging agents in this setting is still inconclusive.
A phase I/II study of TRC105 in combination with sorafenib in hepatocellular carcinoma (HCC).
Authors: Duffy Austin G. , Ma Chi , Ulahannan Susanna Varkey , Makarova-Rusher Oxana V. , Fioravanti Suzanne , Walker Melissa , Venkatesan Aradhana , Turkbey Ismail B. , Choyke Peter L. , Trepel Jane B. , Cao Liang , Compton Kathryn , Figg William Douglas , Greten Tim F. 
Published: February 2017

291 Background: Endoglin (CD105) is an endothelial cell membrane receptor highly expressed on proliferating tumor vasculature, including HCC. CD105 is essential for angiogenesis and its expression is upregulated by hypoxia and VEGF inhibition. TRC105 is a chimeric IgG1 anti-CD105 monoclonal antibody that inhibits angiogenesis and causes ADCC and apoptosis of proliferating endothelium. Sorafenib is the only FDA-approved drug in HCC. Methods: Preclinical: Murine BNL HCC cells were grown subcutaneously in wildtype Balb/c mice and treated with antibody to murine CD105, (clone MJ7/18; 10-200ug) + sorafenib (10 mg/kg daily p.o.) or sorafenib alone with assessment for CD105 expression, tumor size. Clinical: Patients with HCC (Childs Pugh A/B7), ECOG 0/1, were enrolled in a phase I study of TRC105 at 3, 6, 10, 15mg/kg q 2wks plus sorafenib 400mg bid. Correlative biomarkers included DCE-MRI, color Doppler ultrasonography, circulating endothelial and endothelial progenitor cells, plasma levels of angiogenic factors, soluble CD105 and tumor IHC for CD105. Samples were also collected for immunogenicity and pharmacokinetics. Results: Preclinical studies: CD105 expression was increased in BNL HCC tumors by sorafenib. Anti-CD105 antibody + sorafenib reduced tumor volume compared to sorafenib alone. Clinical trial: 19 pts were enrolled; Hep B/C/NA: 2/10/7; M:F 13:6; Mean age of 60 (range 18-76); 1 DLT (increased AST) occurred at 10mg/kg. Three of 14 (21%) evaluable pts achieved PR by RECIST. Four patients had confirmed stable disease, one of whom was treated for 22 months. Median time on study was 4 months (range 2 to 22 months). Conclusions: TRC105 combined with sorafenib was well tolerated at the recommended single agent doses of both drugs. Encouraging evidence of activity was observed and the study is proceeding to the phase 2 stage. Full correlative and clinical data will be presented. Clinical trial information: NCT01306058.
The association of HGF/Cmet overexpression with clinicopathologic factors in hepatocellular carcinoma.
Authors: Goff Laura Williams , Shaikh Fyza Y , Du Liping , Washington Mary Kay , Salaria Safia N 
Published: February 2017

297 Background: The Cmet receptor tyrosine kinase is overexpressed in 20-50% of hepatocellular cancers (HCC) and has been associated with aggressive features. Little is known about the clinical characteristics of patients whose tumors overexpress Cmet. We examined Cmet expression levels on a series of 80 HCC samples to evaluate for an association between overexpression and clinicopathologic features. Methods: Samples from 80 patients with HCC were assessed with immunohistochemistry (IHC) analysis for hepatocyte growth factor (HGF) and Cmet. Positive staining was correlated with age, sex, race, HCC risk factors, tumor grade, stage, metastatic sites and survival. Results: Hepatitis B virus (HBV) patients were more likely to have Cmet positive tumors than those with other risk factors for HCC such as hepatitis C or alcohol. Higher tumor grade was associated with Cmet positivity. No evidence of association between Cmet positivity and survival was seen although HGF positivity tended to associate with a trend toward decreased survival. Conclusions: Cmet pathway overexpression in HCC is associated with distinct clinical and pathologic features. [Table: see text]
ING3 as a novel regulator of pancreatic cancer growth and aggressiveness.
Authors: Koutsioumpa Marina , Hatziapostolou Maria , Polytarchou Christos , Joshi Swapna , Iliopoulos Dimitrios 
Published: February 2017

304 Background: Recent studies demonstrate that chromatin regulation by posttranslational means, such as histone methylation or acetylation, is an essential control mechanism in tumorigenesis and tumor progression. Accumulative findings support the notion that pancreatic cancer tumorigenesis is not only governed by genetic alterations but also aberrant epigenetic regulation. The aim of the present study was to identify and assess the role of chromatin regulators in pancreatic cancer. Methods: The gene expression profile of chromatin regulators was assessed using gene expression microarray analysis in pancreatic cancer and uninvolved human tissues. Validation of microarray findings was performed by qRT-PCR in two extended cohorts of patients and by immunohistochemistry in pancreas tumor tissue microarrays. PANC-1, MIA Paca-2, Capan-2, HPAF-II and AsPC-1 cell lines were used for in vitro assays. Efficiency of knockdown experiments, performed by RNAi interference assays and shRNA-expressing lentiviral vectors, was evidenced by qRT-PCR and Western Blot Analysis. Cell proliferation, invasion and colony formation assays were conducted in genetically modified cells. The significance of variability between the results from each group and corresponding control was determined by unpaired t-test. Results: Differential expression analysis of chromatin regulators in pancreatic cancer versus uninvolved tissues demonstrates that 27 epigenetic molecules are significantly de-regulated (>1.5 fold, P<0.05). By hierarchical clustering, the samples are classified into two major groups that reflect the normal and cancer state. The decreased expression of inhibitor of growth family member 3 (ING3), a component of the NuA4 histone acetyl-transferase complex, was further validated by qRT-PCR and immunohistochemistry analysis in tumor tissues. Transient or stable silencing of ING3 caused significant increase of viability, proliferation, colony formation and invasion in several pancreatic cell lines. Conclusions: Our data show that human pancreatic cancer is characterized by loss of ING3 expression and we defined a potential role of the latter in pancreatic cancer cell growth and invasion.