bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risks of thromboembolic events among patients diagnosed with metastatic pancreatic ductal adenocarcinoma treated with chemotherapy.
Authors: Bapat Bela , Bhurke Sharvari , Rosen Edward , Stokes Michael , Bhagnani Tarun , Nordstrom Beth , Zaknoen Sara , Qadan Ammar 
Published: February 2017

380 Background: Clinical trials suggest that patients with metastatic pancreatic ductal adenocarcinoma (mPDA) are at a high risk of thromboembolic events (TEs) as a result of both disease and treatment. Real-world data on TE rates are limited for patients with mPDA. Methods: Using a retrospective cohort design, patients with mPDA aged ≥ 65 years and treated with chemotherapy during 2007-2012 were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients enrolled in Medicare parts A, B, and D were followed from the start of first-line chemotherapy (index date) to the earliest of disenrollment from Medicare, death, or 12/31/2012. The baseline (BL) period was defined as 12 months prior to the index date. The incidence of TEs was calculated as the number of events per 100 person-years (PY) of follow-up (F/U) among patients without a BL TE. Anticoagulant use during F/U was categorized as preventive (before first TE, if any) and treatment (on or after first TE date) among patients with no BL TE. Results: Of 1,308 patients meeting the selection criteria, the mean age was 74 years, and 56% were female. The prevalence of TEs during the study period (BL or F/U) was 58% (n = 755). Excluding the 427 patients (33%) with TEs during BL, 328/881 (37%) of patients had a first TE during F/U, for an incidence rate of 85/100PY, including 29/100PY arterial and 59/100PY venous events. In the full study cohort, only 467/1,308 (36%) had a claim for any anticoagulant during the study period, although inpatient anticoagulant use is likely under-reported. Among patients receiving anticoagulants, 287/467 (61%) received low molecular weight heparin (LMWH). Preventive anticoagulant use was observed in 74/881 (8%) of patients without a BL TE; anticoagulation treatment was observed for 159/328 (48%) patients with a first TE during F/U. Conclusions: Real-world mPDA patients face a significant risk of TEs both before and after starting chemotherapy. Although inpatient use of anticoagulants including LMWH is incomplete in this database, it is clear that use of anticoagulants for treatment, and for prevention, of TEs is sub-optimal.
Towards an absolute bilirubin threshold for preoperative biliary decompression in patients undergoing whipple.
Authors: Mosquera Catalina , Dorismond Vanessa G. , Zervos Emmanuel E. 
Published: February 2017

381 Background: There is no consensus as to when preoperative biliary decompression is indicated in patients with obstructive jaundice prior to pancreatoduodenectomy. The purpose of this study is to identify a bilirubin level whereby biliary decompression provides clear benefit despite potential drawbacks. Methods: Serial logistic regression analyses were undertaken to identify the bilirubin threshold upon which biliary decompression was associated with significant improvement in overall complications, mayor complications (Clavien-Dindo ≥ 3), length of stay, readmission rates and mortality. Results: Biliary decompression independently predicted a higher incidence of overall complications in patients presenting with bilirubin ≤ 10mg/dl, (p = 0.02). For patients with bilirubin > 10mg/dl - < 15mg/dl, there were no differences in complications, mortality, length of stay or readmissions. Biliary decompression in patients with bilirubin ≥ 15mg/dl independently predicted fewer overall (72% vs 100%), and mayor complications (11 % vs 50%), p < 0.05, and lower readmission rates (27.7% vs 62.5%), p = 0.02. Patients not undergoing biliary decompression underwent resection on average two weeks sooner than those having decompression (4.7 days vs 17.2 days), p = 0.01, with no significant change in bilirubin levels between presentation and surgery. Patients with bilirubin < 15mg/dl at presentation, who underwent biliary decompression, had a bilirubin decrease of more than 50% ( 6.3mg/dl to 2.5mg/dl), and the time to resection increased by more than one week (28 days vs 20.4 days), p < 0.001. Conclusions: All patients presenting with bilirubin ≥ 15mg/dl should undergo preoperative biliary decompression to minimize the risk of complications and readmissions. Patients presenting with bilirubin ≤ 10 mg/dl should forego stent placement to avoid stent related complications without clear benefit. The decision to stent between > 10mg/dl to < 15 mg/dl should be made on a case by case basis, taking into account anticipated bilirubin level at the time of surgery.
Nutritional status and outcomes of older versus younger patients (pts) with metastatic pancreatic cancer (mPC).
Authors: Vijayvergia Namrata , Seo Jenny Y , Devarajan Karthik , Denlinger Crystal Shereen , Cohen Steven J. , Dotan Efrat 
Published: February 2017

386 Background: Older mPC pts are less likely to receive chemotherapy (Ctx) and receive fewer agents compared to younger pts, yet have similar overall survival (OS). Both obesity and malnutrition are linked with poorer outcomes in pancreatic cancer. We evaluated the effect of body mass index (BMI) and nutritional state on survival in < 65 y (GpA) and > 65 y (GpB) mPC pts. Methods: With IRB approval, we retrospectively analyzed charts of 579 mPC pts treated between 2000 and 2010. GpA and GpB were compared based on BMI alone (<19, 20-25 and >25) and also their nutritional status (poor: albumin <3 or weight loss>15% during disease course with any BMI; good: Alb>3.5 + Wt loss<15% + BMI >20; intermediate: all others). Log-rank tests and Cox proportional hazards models were used to analyze OS and Fisher’s exact test to compare categorical variables. Results: There were 299 pts in GpA (median age 57yr) and 280 pts in GpB (median age 73 yr). Information on BMI/albumin was missing for 126 pts; total study population was 454 (GpA 238, GpB 216).Groups were well balanced for gender (majority male), PS (majority ≤1), initial stage (majority IV), and primary site (majority head). There was no significant difference in Ctx and number of agents used between the 3 subgroups across GpA and GpB. BMI alone did not affect survival in both groups. Nutritional status was significantly associated with survival when evaluating the whole population and GpA, but not GpB (Table). Good nutrition GpA pts had a lower relative risk of death versus pts in intermediate and poor nutrition groups (RR 0.83, CI 0.71-0.96, p=0.02). Good nutritional status was associated with better survival in GpA on multivariate analysis (RR=0.81, CI 0.69-0.95; p=0.008,), but not in GpB. Conclusions: Nutritional status (defined by BMI, albumin and weight loss) was associated with survival in younger mPC pts but not in older pts. Greater attention to nutrition and cancer cachexia with possible interventions throughout treatment may improve survival in mPC pts undergoing chemotherapy, especially those < 65 yrs. Table [Table: see text]
Novel nomogram combining depth of invasion and size to predict the benefit of regional lymphadenectomy for appendiceal neuroendocrine tumors (A-NET).
Authors: Mosquera Catalina , Vora Haily , Fitzgerald Timothy Louis 
Published: February 2017

389 Background: The need for regional lymphadenectomy for A-NET is predicated on the risk of nodal metastasis. Although depth of invasion is predictive of nodal metastases in other gastrointestinal NET, current guideline recommendations for A-NET are based solely upon size. Methods: Patients with A-NET from 1988-2012 were identified within the SEER registry. Depth of invasion was defined as limited to lamina propria (LP), invading or through muscularis propria (MP), and through serosa (TS). Results: A total of 1,024 patients met inclusion criteria, with majority being female (55.7%), white (86.8%), and node-negative (81.1%). On univariate analysis, risk of nodal metastases was associated with size ( < 1 cm 1.9%, 1-2 cm 19.7%, 2-4 cm 32.5%, and > 4 cm 37.2%), depth of invasion (LP 4.1%, MP 17.4% and TS 44.3%) and extent of surgery (appendectomy 8.7% vs colectomy 31.9%), p < 0.0001. On multivariate analysis, size ( < 1 cm vs 1-2 cm HR 8.80, vs 2-4 cm HR 15.68, and vs > 4 cm HR 15.16), depth of invasion (LP vs TS HR 6.67) and extent of surgery (appendectomy vs colectomy HR 2.98), continued to be associated with nodal involvement, p < 0.0001. When only patients with colectomy were considered results were similar on both univariate and multivariate analyses. On univariate survival analysis, size [ < 1cm 95.6%, 1-2cm 94.9%, 2-4cm 88.4%, and > 4cm 73.7% 5-year disease-specific survival (5-y DSS)], depth of invasion (LP 96.9%, MP 93.2%, and TS 77.1% 5-y DSS), extent of surgery (appendectomy 94.4% and colectomy 87.1%), and N stage (N0 94.7% and N1 77.7%) predicted survival, p < 0.002. In a Cox regression model, extent of surgery and N stage continued to predict survival. A nomogram was created to predict the risk of nodal metastases, AUC = 0.83. Conclusions: This simple nomogram, which incorporates size and tumor extension, accurately predicts the risk for regional nodal metastases in appendiceal NET. In addition to providing valuable information on risk for regional nodal metastases, depth of invasion independently predicts survival.
Palliative care for hepatocellular carcinoma: Analysis of the National Cancer Data Base.
Authors: Hammad Abdulrahman Y , Robbins Jared , Turaga Kiran , Christians Kathleen K. , Gamblin T. Clark , Johnston Fabian McCartney 
Published: February 2017

390 Background: Palliative care is provided to a subset of hepatocellular carcinoma (HCC) patients with the aim of symptomatic relief and improving quality of life. The present study sought to assess and compare the prevalence and efficacy of different palliative therapies for HCC from the National Cancer Database (NCDB). Methods: The NCDB, a retrospective national database that captures approximately 70% of all patients treated for cancer, was queried for patients with HCC who were deemed non-resectable from 1998-2011. Patients were stratified by receipt of palliative care. Descriptive analyses were performed. Survival analysis was examined by log-rank test and Kaplan Meier curves, and a multivariate proportional hazards model was utilized to identify the predictors of survival. Results: A total of 3,267 patients were identified; 287 (8.7%) received surgical palliation, 827 (25.3%) received radiotherapy, 877 (26.8%) received chemotherapy, 1,067 (32.6%) received pain therapy, while 209 (6.4%) received a combination of the previous 3 modalities. The median age was 61 (54-72), and 81.3% of the patients were males, and of Caucasian ancestry (72.5%). Difference in the Charlson Comorbidity Index (CCI) existed between the comparison groups (p< 0.001). On a multivariate hazards model, palliative radiotherapy was identified as a positive predictor of survival (Hazards Ratio (HR): 0.71 [95%CI:0.56-0.90]), while pain therapy was a negative predictor of survival (HR: 1.79 [95%CI: 1.43-2.25]). Stratifying by disease stage, palliative radiotherapy provided a significant survival benefit for patients with stage IV disease. Examining the RT cohort, most patients received external beam radiation (80%) and palliative radiation was most frequently delivered to the spine (35%) followed by the liver (19%). The survival benefit was more significant when the liver was targeted (OS: 3.7 months vs. 7.3 months, p= 0.03). Conclusions: Amongst the palliative therapies examined, radiotherapy appear to extend survival and should be considered for patients presenting with late stage HCC. Pain therapy alone acts as a negative predictor of survival and should not be considered as a sole intervention for patients with late stage disease.
Intraoperative radiotherapy (IORT) in the era of intensive neoadjuvant chemotherapy and chemoradiotherapy for locally advanced and borderline resectable adenocarcinoma of the pancreas (PDAC).
Authors: Keane Florence K. , Wo Jennifer Yon-Li , Ferrone Cristina , Clark Jeffrey W. , Blaszkowsky Lawrence Scott , Allen Jill N. , Kwak Eunice Lee , Ryan David P. , Lillemoe Keith D , Fernandez-del Castillo Carlos , Hong Theodore S. 
Published: February 2017

393 Background: Improved outcomes with FOLFIRINOX or gemcitabine with nab-paclitaxel in the treatment of metastatic PDAC have prompted incorporation of these regimens into neoadjuvant treatment of PDAC. While some patients are still found to be unresectable after neoadjuvant treatment, others are able to undergo resection. Our aims are to evaluate outcomes and toxicities associated with use of IORT in this setting. Methods: We retrospectively analyzed records of 85 patients with locally advanced/ borderline resectable PDAC who received neoadjuvant treatment with chemotherapy and/or chemoradiotherapy followed by surgical exploration in an IORT-equipped operating suite between 2010-2015. Descriptive statistics were used to compare surgical outcomes. Survival analysis was used to calculate overall survival (OS). Results: Of 85 patients, 49 (57.6%) underwent resection after neoadjuvant treatment, 27 (31.8%) were unresectable, and 9 (10.6%) were found to have distant metastases. 24 of 49 patients who underwent resection received IORT for close/positive margins on intraoperative frozen section. There was no significant difference in operative times, postoperative complications, or operative morbidity in patients who underwent resection and IORT vs those who underwent resection alone. Median OS was 31.1 months in patients who underwent resection alone and 35.1 months in patients who underwent resection and IORT. Despite the increased incidence of close/ positive margins in patients who underwent resection and IORT, the rates of local recurrence were similar to those who underwent resection alone. 26 of 27 patients with unresectable disease upon exploration received IORT. Median OS was 20.5 months. IORT was associated with increased hospital stay (4 vs. 3.5 d), but no significant difference in operative time or morbidity. Conclusions: IORT is not associated with increased toxicity when used in conjunction with resection or surgical exploration after neoadjuvant therapy. IORT resulted in median OS of 35 months for patients with close or positive margins and of 20.5 months for patients with unresectable disease.
Rapid immunohistochemical analysis of pancreatic cytology from endoscopic ultrasound-guided fine-needle aspirates: A prospective clinical trial.
Authors: Tsai Susan , Ritch Paul S. , Erickson Beth , George Ben , Johnston Fabian McCartney , Mackinnon Alexander C. , Evans Douglas B. , Christians Kathleen K. 
Published: February 2017

400 Background: Acquisition of pancreatic cancer (PC) tissue specimens from endoscopic ultrasound-guided fine needle aspirates (EUS-FNA) is crucial to investigational pancreatic cancer trials seeking to utilize molecular profile directed therapy. Methods: In an ongoing prospective clinical trial we have utilized molecular profiling of EUS-FNA specimens from patients with resectable and borderline resectable pancreatic cancers. Cytologic specimens were evaluated for six biomarkers to guide the choice of neoadjuvant therapy: secreted protein acid rich in cysteine (SPARC), thymidylate synthase (TYMS), ribonucleotide reductase M1 (RRM1), human equilibrative nucleoside transporter 1 (ENT1), excision repair cross-complementing 1 (ERCC), and topoisomerase 1 (TOPO). Final immunohistochemical (IHC) interpretation was scored by a single pathologist using both staining intensity and percent immunochemically reactive cells. Results: The trial has enrolled 99 patients to date; 47 (47%) resectable patients and 52 (52%) borderline resectable patients. No patient experienced a EUS-FNA related complication. IHC profiling was reported in a median of 5 business days (IQR:3). Of the 99 patient samples, 73 (74%) had adequate cellularity for IHC profiling and this was not affected by stage of disease (n = 35, resectable; n = 38 borderline resectable; p = 0.82). Analysis of SPARC expression was limited to specimens with adequate stromal cells for analysis (n = 50, 51%). Among the 73 patients with adequate tissue for profiling, expression profiling was interpreted to be favorable for the following therapeutic agents: nab-paclitaxel, (SPARC, n = 35, 48%), 5-fluorouracil (TYMS, n = 68, 93%), gemcitabine (RRM1, n = 34, 47%; ENT1, n = 38, 52%), platinum agents (ERCC, n = 30, 41%), and irinotecan (TOPO, n = 62, 85%). Conclusions: The use of EUS-FNA specimens for molecular diagnostics is feasible and IHC analysis was possible in 74% of patient specimens, with preservation of stromal components in over 50%. Further refinement of molecular techniques may expand the breadth of analysis which may be performed, to include quantitative polymerase chain reaction and genetic sequencing Clinical trial information: NCIT01726582.
Bridging therapy effectiveness in the treatment of hepatocellular carcinoma prior to orthotopic liver transplantation.
Authors: Zlobinsky Rubinstein Maria M , Kaubisch Andreas , Kinkhabwala Milan , Reinus John , Liu Qiang , Chuy Jennifer W. 
Published: February 2017

401 Background: Orthotopic liver transplantation (OLT) is the only curative intervention for both hepatocellular carcinoma (HCC) and underlying cirrhosis. OLT is limited by both donor organ shortages and long waitlists for transplant. In order to halt tumor progression, various bridging therapies (BT) have been utilized. Despite complete radiologic responses following BT, viable tumor is often present on explant analysis. We present an update of our experience and include novel bridging modalities. Methods: 35 patients were retrospectively evaluated in a transplant center prior to OLT for HCC. A total of 68 locoregional therapies were utilized. Success of BT was assessed by radiologic response and histopathological examination of the explanted livers. Results: 61 nodules were studied in liver explants. Pre-transplant treatments included: TACE, alcohol ablation (ETOH), radiofrequency ablation (RFA), microwave ablation, selective internal radiation therapy (SIRT) and stereotactic body radiation therapy (SBRT). Radiologically, 36 nodules (59 %) achieved complete response compared to 20 nodules (33%) on explant analysis. Approximately 1/3 of treated nodules with complete tumor necrosis (CTN) were treated with TACE + RFA. 60% of nodules (12/20) with CTN were treated with more than one bridging modality. 75% of nodules (3/4) treated with SIRT alone showed CTN. Patients underwent a mean of 2.2 BT. Four out of 35 (11%) patients had no residual HCC on explant analysis. Conclusions: Although favorable radiologic responses are seen following BT, viable HCC is often seen in liver explants. Newer strategies like SIRT may enhance locoregional control and should be explored as part of an aggressive approach for patients awaiting transplant. [Table: see text]
The minimal effective relative dose intensity (RDI) for modified FOLFIRINOX in advanced pancreatic cancer: Suggestion for modified Hryniuk’s calculation method.
Authors: Lee Jong-chan , Paik Kyu-hyun , Kim Hyoung Woo , Kang Jingu , Park Young Soo , Kim Jaihwan , Hwang Jin-Hyeok 
Published: February 2017

402 Background: Since FOLFIRINOX (5-fluorouracil, oxaliplatin, leucovorin and irinotecan) improved efficacy but also increased toxicity in pancreatic ductal adenocarcinoma (PDA) patients, several reports have been published about modified FOLFIRINOX as a concept of dose reduction. However, the lower limit of dose reduction is still unclear. The aim of this study is to find the minimal relative dose intensity (RDI, %) of FOLFIRINOX that can be expected to yield tumor response in advanced pancreatic ductal adenocarcinoma. Methods: A total of 95 PDA patients treated with FOLFIRINOX as a first line therapy were retrospectively reviewed. Based on Hryniuk’s arithmetic formula, we defined an extended Hryniuk’s calculation and launched a calculator site ( http://www.rdicalc.com ). Using receiver operator characteristic (ROC) curve, we investigated minimal RDI with a view to obtaining tumor response rate (RR) and disease control rate (DCR). The toxicity profile was also described. Results: Among the 95 patients, 85 patients completed the initial treatment until the first radiological evaluation with median 3 cycles and 56 days. Thirty one patients had locally advanced PDAC and 54 had metastatic disease. As the minimal effective thresholds, the ROC curve showed 71.5% RDI for RR (78.1% sensitivity, 83.0% specificity) and 54.5% RDI for DCR (91.3% sensitivity, 56.3% specificity). When divided by 5% units, the minimal RDI for RR and DCR was 70% and 55%, respectively. Among the 95 patients, including the dropout group, grade III/IV neutropenia, febrile neutropenia and vomiting was 45%, 13% and 31%, respectively. Early period toxicities and RDI did not show dose-response relationships. Conclusions: Although reduced dose FOLFIRINOX could be effective in advanced PDAC, our data suggest that more than 70% RDI for RR and 55% for DCR should be preserved. Toxicity rates were not influenced by RDI level in the early therapeutic period.
Correlation between change of FA score and postoperative recurrence in esophageal cancer patients who received neoadjuvant treatment.
Authors: Matsuda Satoru , Takeuchi Hiroya , Fukuda Kazumasa , Nakamura Rieko , Takahashi Tsunehiro , Wada Norihito , Kawakubo Hirofumi , Kitagawa Yuko 
Published: February 2017

41 Background: We previously reported that fibrinogen and albumin score (FA score), which was consisted of plasma fibrinogen level (FNG) and serum albumin level (Alb), was shown to predict postoperative survival in esophageal cancer patients who underwent transthoracic esophagectomy. In this study, in patients who received neoadjuvant chemotherapy (NAC), change of FA score during NAC was reviewed and the correlation with recurrence free survival (RFS) was investigated. Methods: We retrospectively reviewed 125 patients who received neoadjuvant chemotherapy and underwent transthoracic esophagectomy in our institution between 2001 and 2012. FNG and Alb before (preTx) and after (preope) NAC were confirmed in 92 patients. Based on our previous reports, patients with elevated fibrinogen ( > 350 mg/dL) and decreased albumin ( < 3.8 g/dl) levels were allocated a FA score of 2, those with only one of these abnormalities were allocated a FA score of 1, and those with neither of these abnormalities were allocated a FA score of 0. Regarding change of FA score, based on the preTx and preope FA score, we classified into decrease group and increase (no change or increase) group. Patient characteristics, clinicopathological factors, preTx FA score, and preope FA score were reviewed, and correlation with RFS was investigated. Results: The number of preTx and preope FA score 0/1/2 was 39/41/12, 36/37/19. Regarding change of FA score, FA score decreased in 70 patients (76%), increased in 22 (24%). There was no significant difference in patient background and clinicopathological factors between groups. In survival univariate analysis, change of FA score (Increase group, HR 2.023, p = 0.025) were significantly correlated with RFS. In multivariate analysis, using preTx clinical stage as a covariate, FA score was shown to be an independent predict factor (Increase group, HR 2.076, p = 0.023) for RFS significantly. Conclusions: Change of FA score between before and after NAC was shown to be a predictive factor of RFS in esophageal cancer patients who received NAC. Both fibrinogen and albumin are popular indicators routinely measured in daily clinical practice, FA score may be highly validate and feasible.