bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemosensitivity and clinical characteristics of pancreatic malignancies in BRCA mutation carriers.
Authors: Golan Talia , Kanji Zaheer , Epelbaum Ron , Devaud Nicholas , Dagan Efrat , Holter Spring , Aderka Dan , Kaufman Bella , Gershoni-Baruch Ruth , Moore Malcolm J. , Friedman Eitan , Gallinger Steven 
Published: February 2017

278 Background: Somatic inactivation of genes involved in homologous recombination (HR) may confer increased sensitivity to poly (ADP-ribose)- polymerase (PARP) inhibition and DNA cross-linking agents (eg. mitomycin C, platinum-based chemotherapy). Studies in BRCA associated ovarian cancer have demonstrated favorable outcomes with platinum based treatments. The role of BRCA mutations in pancreatic cancer outcome is understudied. In this study, the clinical features and therapeutic responses of BRCA 1/2 mutation carriers with pancreatic malignancies are reported. Methods: Patients with BRCA1/2 -associated pancreatic ductal adenocarcinoma (PDAC) diagnosed between January 1994-June 2012 were identified from clinical databases at three participating institutions. Demographic, clinical, and therapeutic response data were collected and analyzed using non-parametric models. Progression-free (PFS) and overall survival (OS) were analyzed. Results: Overall, 63 patients with PDAC and a BRCA1 (n=17), BRCA2 (n=43) or both (n=1) mutations were included. Mean age at diagnosis was 60.2 (range 33-83), 37 (58.7%) were male, 48 (76.2%) were Jewish, 26 (41.3%) were smokers, 55 (87.3%) had a family history of malignancy of which 18 (32.7%) had a history of PDAC. Twenty-five (39.7%) patients underwent a primary resection, and 30 (47.6%) had stage IV disease at presentation. PFS on platinum-based first-line chemotherapy in 12 metastatic BRCA positive cases (median: 90 days) was not statistically different than that of non-platinum chemotherapy treated carriers (n=18, median: 92 days) (p= 0.6412). Two patients with advanced disease were down-staged from unresectable to resectable using combination gemcitabine/cisplatin therapy. One of these is disease free at 50 months after surgery. Median OS for all 51 patients (excluding patients receiving experimental treatments) was 14.02 months (9.48-18.2). Conclusions: The natural history of BRCA associated PDAC appears similar to non-carriers. The role of platinum agents in these individuals remains unclear as data are not mature, however, to date, no difference in median PFS was observed. Surgical downstaging may be possible in a subset of these patients.
Hepatic artery infusion for recurrentor chemoresistant hepatic malignancy.
Authors: Wanebo Harold J. , Taneja Charu , Cummings Francis , Begossi Giovanni , Belliveau James 
Published: February 2017

295 Background: Previously treated Hepatic Colorectal Metastases (CRC) and advanced hepato cellular cancer (HCC) are tumor challenges frequently unresponsive to systemic chemo therapy (CT). We reviewed survival outcome in chemo resistant / high risk patients following hepatic artery infusion (HAI) in 21 CRC pts, 10 HCC pts, and 6 miscellaneous metastatic cancers. Methods: Patient groups: 21 CRC pts (16M, 5 F), mean age 63: 16 had metachronous (DFI-17 mos), and 5 Synchronous CA; liver extent: 76% multiple (>5) mets or extensive bilateral; CEA (ng/m), >100, 8 pts > 50 (3 pts) ;< 5 (3 pts),UNK(7 pts). Previous CT:FU/LV (11pts), Oxaliplatin (OX) or Irinotecan (IR) (10 pts). Liver surgery: Partial Resection/RFA – 9 pts. HCC – (9 PTS), cholangioCA(1pt); M/F 5/5; av.age 63yr.. Previous RX Hepatic lobectomy 4 pts, RFA/TACE – 3 patients. Miscellaneous GP (therapy): Hepatic lobectomy + HAI were in metastatic lung (1), Breast (1), advanced gall bladder Ca (GBCA) (T 3-4) (2 pts); HAI alone was done in Br. CA (1) carcinoid (1) Treatment Protocols: CRC: HAI-FUDR 12/15mg/kg/d, dexamethasone 2mg.kg/d, leukovorin (20mg/M2/d) X14 d plus bolus (d1), oxaliplatin OX 130 mg/M2 cisplatin CIS, 100 mg/M2; Systemic RX: d20-30. OX I.V. 130mg/M2, capecitabine 750-1,000 mg/M2/d x 10 days (also used in Miscel. Grp.) HCC Protocol: HAI-14 d as in CRC Protocol. Bolus infusion d1-doxorubicin 75mg/M2or OX or CIS as in CRC schema. Results: CRC:OS-CRC post start HAI = med/16 mos., 2yr/5yr = 27%/6%. HCC OS = 9 mos.( Median); 3->41mos in 9 evaluable pts.; 1 HCC pt with recurrence 2 yr. post hepatectomy survived over 3.5 yrs. with HAI + RFA/TACE – (OS-67mo).Miscellaneous group included lung (11 mos) Br CA (23, 9 mos) adv. Carcinoid (3 mos), GBCA (2 pts > 60 mos), Major Complications; Pump malfunction (4 pts), misperfusion (2) pts, infected pocket (2) pt, duodenal fistula (1) pt. Conclusions: Hepatic artery infusion alternating with systemic chemo therapy has apparent survival benefit in selected patients with persistent or progressive chemo resistant malignancy from metastatic CRC, HCC, or selected miscellaneous cancers (breast, lung, liver, gall bladder cancer) and warrants further study.
Predictors for readmission after pancreatic resection for malignancy.
Authors: Newman Naeem A , Lucas John T , Peacock Diandra A , Trottman Paul A , Winters Shira M , Wentworth Sean S , Levine Edward A. , Shen Perry 
Published: February 2017

301 Background: Readmission after pancreatic resection has been reported as high as 50%. This study was undertaken to determine factors predicting readmission after pancreatic resection for malignancy. Methods: We reviewed the medical records of 202 patients to identify patients that had a pancreatic resection for malignancy between 2003 and 2010. Outcome measures included patient characteristics, medical comorbidities, and perioperative factors. Results: A total of 202 patients underwent pancreatic resection for malignancy. AJCC T stage was T1, T2, T3, and T4 in 10.9%, 26.3%, 52% and 9.2% respectively. Pancreatic head malignancies made up 84.8% of the patients, 2.3% were pancreatic neck, 8.4% were pancreatic body, and 4.5% were pancreatic tail primaries. Preoperative biliary stents were placed in 58% of patients. Adjuvant radiation and chemotherapy were given in 47.8 and 61.39% respectively. The readmission rate following resection was 20% at 60 days. The most common reasons for readmission within 60 days were delayed wound healing and renal insufficiency. On univariate analysis, factors predicting higher readmission rates included positive retroperitoneal margin (p=0.048), delayed gastric emptying (p=0.015), and presence of wound infection (p=0.0020). Conclusions: Factors related to tumor burden and GI/infectious complications were the most common predictors of readmission after pancreatic resection for malignancy. Though tumor size is a relatively immutable variable, improved management of postoperative complications remains an important factor in decreasing readmission rates after pancreatic resection for malignancy.
Does interval from histologic diagnosis (Dx) to start of chemotherapy (Ctx) influence survival in advanced pancreatic adenocarcinoma (PC)?
Authors: Teo MinYuen , Jayaram Anuradha , Naidoo Jarushka , Mohd Sharial Mohd Syahizul Nuhairy , O'Brien Michelle , Bajwa Raazi , McDonnell Felicity , Geoghegan Justin , Conlon Kevin C. , Grogan William , Power Derek Gerard , McDermott Raymond S. 
Published: February 2017

306 Background: Pancreatic cancer is known to be aggressive and treatment-resistant. In potentially resectable PC, time from diagnostic imaging to surgery correlates with rates of metastases at laparatomy. In advanced PC, therapeutic benefits of ctx are frequently calculated from start of treatment. In view of its aggressiveness, we investigated if the interval between dx and commencement of ctx influences overall survival (OS) in patients (pts) with advanced PC. Methods: Pts with PC were identified from 4 insitutional databases. Inclusion criteria were unresectable (UPC) or metastatic disease (MPC) and receipt of ctx. Clinicopathologic details were collected. Intervals from histologic dx to ctx were calculated. Analyses were based on receipt of ctx within or after 2 weeks (w), 4w and 6w of dx. OS was presented as hazard ratio (HR) with associated p-value. Results: 212 pts were identified. Median age was 63 years (range: 33 – 83) and 58% were males. 60% of pts had MPC and 24% received doublet ctx. Median number of days from dx to ctx was 24 days (range: 2 – 202). For UPC and MPC, 20 and 31% of pts began ctx within 2w (p=0.08), 48 and 63% within 4w (p=0.03) and 73 and 82% within 6w (p=0.13), respectively. OS for the entire cohort, UPC and MPC were comparable whether ctx was commenced within pre-defined intervals or not (see table). A subgroup of pts treated with doublet ctx was examined. No OS difference was seen when treated within defined time points (HR 1.1, 1.0, 1.5; p=0.76, 0.96, 0.43). For 77% of MPC with hepatic metastases, no improvement in OS in relation to time interval was noted (HR 1.5, 1.0, 1.1; p=0.10, 0.90, 0.85). For 21% of MPC with ≥2 metastatic sites, ctx within 4w and 6w might improve OS but significance was not reached (HR 0.65, 0.61; p=0.43, 0.46). Conclusions: Commencement of ctx for PC could be delayed due pts-, disease- or infrastructural factors. Our data did not suggest a detrimental effect on OS from ctx delay. However, the lack of survival benefit from early ctx might be due to less effective ctx or inherent aggressiveness of the disease. [Table: see text]
Racial differences in patients with hepatocellular carcinoma: A large single-institution experience.
Authors: Venepalli Neeta K. , Nair Tad D. , Berg Stephanie A. , Modayil Mary , Gaba Ron C. , Bui James T. , Huang Yue , Cotler Scott 
Published: February 2017

318 Background: Hepatocellular carcinoma (HCC) disproportionately affects minorities with higher age-adjusted incidence and mortality rates in Hispanics (H) and blacks (B) versus non-Hispanic whites (C). While H have the fastest rising rates of HCC of all ethnic groups per SEER analysis, little is known about race specific risk factors and disease characteristics. Methods: We retrospectively reviewed HCC patients (pts) treated at University of Illinois-Chicago between 1998 and 2005. Demographics, disease characteristics, treatment patterns, and survival were analyzed with descriptive statistics and chi-square p values. Results: Mean age of HCC pts (N=195) at diagnosis was 59.7 years + 9.8 (19.5% female; 22% aged 65 or older; 61.5% Medicare or Medicaid; 4.1% without insurance; 22.6% H; 31.2% B). Compared to C and B, H pts were more likely to have ascites and NASH and less likely to have ever smoked or have hepatitis C. Compared to B, H pts were more likely to have metabolic syndrome, diabetes, and encephalopathy (HE). Compared to C, B pts had lower MELD scores. Conclusions: In our patient population, Hispanic patients were significantly more likely to have diabetes and NASH, and lower frequency of tobacco use, HCV, and elevated AFP levels at diagnosis. [Table: see text]
Comparative effectiveness and survival benefit of various treatment modalities in HCC: A SEER-Medicare analysis.
Authors: Hanna Nader , Breunig Ian Michael , Mullins C. Daniel , Seal Brian S. , Chirikov Viktor , Shaya Fadia T. 
Published: February 2017

319 Background: In the United States, the incidence of HCC has increased from 1.6 per 100,000 in 1975 to 4.9 per 100,000 in 2005. Care for HCC patients remains specialized and complex with transplant and surgery offering the only potential for long survival. However no comparative effectiveness of various treatment modalities across various stages of HCC exists. Methods: Medicare enrollees, older than 65 with an initial diagnosis of primary HCC between 2000-2007 were followed up through the end of 2009. For patients with stages I, II, III, and unstaged, data were obtained from the SEER and linked Medicare databases, with claims generated from Medicare parts A and B. Multivariate Cox proportional hazards models were used to assess overall and HCC related mortality in relation to receipt of various/no treatments, adjusting for concomitant therapies, demographics, general health status (Charlson comorbidity index), and liver conditions, moderate-severe liver disease. Results: Distributions across stages: males 64-71%, Caucasians 72-77%, African Americans 8-10%, Hispanics 12-14%; a majority (72-75%) was age 65-84; Hepatitis C was the most prevalent (17-41%). Conclusions: Compared to untreated patients, improved all-cause and HCC-related mortality was observed in all stages in the following order: transplant, surgical resection, liver directed therapy, and chemotherapy. Greater impact on HHC-related mortality was seen across all treatment groups. [Table: see text]
MicroRNA polymorphisms and esophageal cancer outcome.
Authors: Faluyi Olusola Olusesan , Eng Lawson , Qui Xin , Cheng Dangxiao , Renouf Daniel John , Marsh Sharon , Savas Sevtap , Knox Jennifer J. , Darling Gail Elizabeth , Wong Rebecca , Xu Wei , Azad Abul Kalam , Liu Geoffrey 
Published: February 2017

32 Background: Better understanding of the biology of esophageal cancer may help improve its treatment. MicroRNAs (miRs) regulate mRNA and can exert some influence on carcinogenesis. Identification of the microRNAs which regulate esophageal cancer development could potentially yield alternative therapeutic options. Objectives: We evaluated polymorphisms in miRs, miR biogenesis, binding sites of miR and their role in the survival of esophageal cancer patients. Methods: 324 esophageal cancer patients of all stages and histological subtypes were evaluated. Using Illumina Custom GoldenGate, 43 polymorphisms in miR pathways were evaluated. Cox proportional hazards models adjusted for clinical prognostic variables and determined the association of polymorphisms with overall survival (OS) and progression free survival (PFS). Adjusted hazard ratio (aHR) and 95% confidence intervals (CI) were calculated. Results: Among our patients, 83% were male while the mean age was 65 years. 73% had adenocarcinomas while 33.6% had advanced tumors (Stage IV). The median PFS was 1.20 years, while median OS was 2.17 years. After adjustment for clinical variables, a 5’UTR polymorphism in pri-mir26a-1 (rs7372209) was significantly associated with reduced PFS [aHR=0.78, CI:0.62-0.98, p=0.04] and OS [aHR 0.71 (0.56-0.89), p=0.003]. Three other polymorphisms were significantly associated with OS but not PFS: these included two polymorphisms of miR processing genes, DDX20 (rs197412) [aHR 1.31 (1.04-1.64), p=0.02] and EIF2C1 (rs595961) [aHR 0.76 (0.60-0.97), p=0.03] as well as the CD86 3’UTR C>G (rs17281995) polymorphism, which has been predicted to affect the binding of miR337, miR582, miR200a, miR184, and miR212 [aHR 1.38 (1.03-1.85), p=0.03]. Conclusions: We report the initial association of miR related polymorphisms with survival in esophageal cancer. We plan to explore additional relationships and validate these findings in other datasets.
Adjuvant chemotherapy in the management of cholangiocarcinoma: A 10-year cohort analysis.
Authors: Shaikh Tahir M. , Asmis Timothy R. , Jonker Derek J. 
Published: February 2017

330 Background: The evidence regarding treatment outcomes from chemotherapy for cholangiocarcinomas (CCAs) is limited because of the high mortality rate and a low overall incidence. Most studies are small and include a heterogeneous group of tumors (biliary, pancreatic, hepatocellular, and ampullary cancers) that each have a unique natural history and response to chemotherapy. The aim of this study is to assess the effect of chemotherapy on survival of patients with surgically resected (R0-negative margins/R1-positive margins) and unresectable (R2-gross residual tumor/metastatic) CCAs. Methods: In a retrospective single-center study, data on all CCA patients (n=209) from 1998 to 2008 were evaluated. Survival time was assessed as a primary outcome measure. Patient demographics, pathological diagnosis, performance status, chemo-radiation therapy, surgical resection, relapse rates and laboratory outcomes were assessed. Results: 209 cases of CCA (female n=116, mean age 65, adenocarcinoma n=166 (79.4%), stage 0/1 n=17 (8.1%), stage 2/3 n=99 (47.3%), stage 4 n=93 (44.4 %)) were identified. 162 (77.5%) patients received treatment (surgical resection n=118 (R0 n=53, R1 n=21) chemotherapy n=85, radiation therapy n=33). Median overall survival (months) was 9.8 (no treatment =2.1, treatment =12.4 (R0 and R1 surgical resection =21.9 and 10.9 p<.001). Median survival (months) in patients with surgical resection with and without adjuvant chemotherapy was 22.2 vs 21.9 p=0.75 for R0 resection and 18.1 vs 10.9 p=0.10 for R1 resection. In patients with unresectable tumor, median survival with and without chemotherapy was 10.7 and 2.1 months (p<.05) respectively. Conclusions: CCAs are associated with poor survival if untreated. Complete surgical resection was associated with significantly improved survival outcomes. Adjuvant chemotherapy in the setting of R0 resection did not improve survival compared to surgical monotherapy. In the setting of unresectable or metastatic CCA, survival was significantly prolonged in patients who received palliative chemotherapy. Although not conclusive, these data suggests the use of adjuvant chemotherapy in the setting resection with positive margins (R1) may also prolong survival.
A molecular profile of colorectal cancer to guide prognosis and therapy after resection of primary or metastatic disease.
Authors: Uronis Joshua M. , VanDeusen Jeffrey Bryan , Datto Michael B. , Lucas Joseph , Morse Michael , Mantyh Christopher , Lyerly H. Kim , Clary Bryan M. , Hsu Shiaowen David 
Published: February 2017

339 Background: Biomarkers used to identify patients at high risk for recurrence after surgical resection of colorectal cancer (CRC) lack predictive capacity and are applicable only to localized disease. As the use of adjuvant therapy in this setting can be controversial, the development of a biomarker that is prognostic, predictive, and applicable after resection of primary or metastatic disease may dramatically improve patient outcomes. Methods: We compiled microarray data from 850 patients with predominantly primary CRC from four publically available datasets to predict activity of 19 oncogenic pathways to generate patterns of pathway deregulation for each patient tumor. Mixture modeling was applied to the samples using affinity propagation to subgroup tumors bearing unique patterns of pathway deregulation. The model was then applied to a dataset of 133 predominantly metastatic CRC samples from patients undergoing curative surgical resection at the Duke University Medical Center. Results: Mixture modeling resulted in the identification of 6 distinct molecular subgroups of CRC (MSCC) based on pathway deregulation for both primary and metastatic CRC. Kaplan-Meier analysis of the primary data set revealed differences in recurrence free survival among the 6 MSCC (p=0.0004) with patients assigned to MSCC3 having the poorest prognosis and patients assigned to MSCC4 having the best prognosis. A similar result was obtained when the model was applied to the metastatic data set (p<0.05). Comprehensive analysis of 41 oncogenes showed that no specific mutations were associated with the any of the subgroups. Finally, we observed that MSCCs demonstrate differential sensitivity to specific targeted agents such as MSCCs 1, 2 and 3 to inhibition of Her2 by Lapatinib and EGFR by erlotinib (p<0.05). Conclusions: Prediction of oncogenic signaling pathway deregulation is a powerful tool that may be used to molecularly sub-classify CRCs into clinically relevant subgroups. These subgroups have prognostic implications for recurrence following surgical resection and may help to identify therapies in the adjuvant setting after resection of either primary or metastatic disease.
The impact of aspirin and statin usage on the likelihood of advanced neoplasia at colonoscopy following a positive FOB screening test.
Authors: Mansouri David , Mcmillan Donald C. , Crighton Emilia M , Horgan Paul G. 
Published: February 2017

346 Background: There is increasing evidence that non-steroidal anti-inflammatory drugs, in particular aspirin, and statins can reduce the incidence and progression of colorectal cancer. However, studies examining this relationship within colorectal cancer screening are limited. Therefore the aim of the present study was to assess the impact of aspirin and statins on an individual’s risk of advanced neoplasia in a colorectal cancer screening programme. Methods: A prospectively maintained database of all patients in the first round of screening (April 2009 to March 2011) in our geographical was analysed. Medication usage was recorded prospectively at pre-colonoscopy assessment. The outcome measure was advanced neoplasia, which was defined as cancer or an intermediate or high risk adenomata (>2 polyps, or > 1 polyp >1cm). Results: 4,631 individuals underwent colonoscopy following a positive FOBt of which complete results were available for 4,188 (90%) pts. Overall, 657 (16%) were on aspirin, 880 (21%) were on statins and 537 (13%) were on both. Colorectal pathology was associated with a positive FOBt in 3,043 (73%) pts. Aspirin usage was associated with a reduced likelihood of colorectal pathology being identified (OR 0.79 (0.66-0.95) p=0.012). In the 3,043 pts in whom colorectal pathology was identified, advanced neoplasia was seen in 1,704 (56%) pts. Patients with advanced neoplasia were more likely to be older (OR 1.38 (1.19-1.59)) and male (OR 1.66 (1.43-1.94)) (both p<0.001). In contrast, those on aspirin (OR 0.68(0.56-0.83)), statins (OR 0.65 (0.55-0.78)) or both (OR 0.69 (0.55-0.86)) were less likely to have advanced neoplasia at colonoscopy (all p<0.001). On multivariate analysis, use of both aspirin and statins (OR 0.60 (0.48-0.75) p<0.001) remained independently associated with less advanced neoplasia. Conclusions: In patients undergoing colonoscopy following a positive FOBt with documented evidence of statin or aspirin usage, advanced neoplasia was less likely to be found. This suggests that usage of these medications may have a chemopreventative effect within the context of screening for colorectal cancer.