bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discharge to a skilled nursing facility as the strongest modifiable risk factor for readmissions following pancreaticoduodenectomy.
Authors: Mirkin Katelin Anne , Hollenbeak Christopher S , Cooper Amanda Beth , Gusani Niraj Jaysukh 
Published: March 2017

435 Background: Pancreaticoduodenectomy is a technically difficult and notoriously morbid procedure. As payers begin to link reimbursement to readmission rates, there is growing interest in understanding and preventing readmissions. The objective of this study was to evaluate factors contributing to 30-day readmission rates for patients undergoing pancreaticoduodenectomy. Methods: Data from the Pennsylvania Health Care Cost Containment Council (PHC4) were reviewed for patients undergoing pancreaticoduodenectomy from 2011-2014 (n = 1,552). Outcomes included 30-day readmission and length of stay (LOS). Univariate comparisons were performed between characteristics of those readmitted (n = 404) and not readmitted (n = 1,148). Readmission and LOS were modeled using multivariate logistic regression and linear regression, respectively. Results: Of the 404 (26.0%) patients who were readmitted, the most common causes for readmission were post-operative infection (26.2%), anastomotic complications (8.0%), and dehydration (5.7%). Patients who were readmitted were more likely to be discharged to a skilled nursing facility (SNF) and were associated with a longer LOS of index admission (p < 0.001, both). In multivariate analysis, black race (HR 1.96, p = 0.001), discharge to a SNF (HR 1.73, p = 0.006) and increased LOS (HR 1.36, p = 0.019), were associated with increased odds of readmission. After controlling for patient, admission, and facility characteristics, black race, urgent and emergent admissions, and discharge to a SNF or home with home healthcare, were predictive of a longer LOS (p < 0.05). High surgeon volume, and high hospital volume were associated with a shorter LOS (p < 0.05). Conclusions: The most common causes of readmission following pancreaticoduodenectomy in Pennsylvania from 2011-2014 were post-operative infection, anastomotic complications, and dehydration. Patients with a longer initial hospital stay and those discharged to a SNF were associated with higher odds of readmission. Understanding the interplay of these factors may result in opportunities to prevent readmissions, and improve outcomes in patients undergoing this complex surgery.
Correlation of circulating IL-8 levels with improved overall survival in advanced pancreatic cancer patients in response to antisense OT-101 (trabedersen) therapy.
Authors: Trieu Vuong N. , D'Cruz Osmond , Qazi Sanjive , Ng Kevin , Hwang Larn 
Published: March 2017

444 Background: Overexpression of the transforming growth factor-beta 2 (TGF-β2) has been suggested as a pivotal factor for malignant progression of pancreatic cancer (PAC). OT-101 (Trabedersen) is a phosphorothioate antisense oligodeoxynucleotide target the human TGF-β2 mRNA. A Phase I/II study of OT-101 was characterized by outstanding overall survival (OS) in patients with advanced PAC. In this study, we examined the association between plasma levels of 31 cyto-/chemokines and OS outcomes in PAC patients treated with OT-101. Methods: Plasma levels of 31 cyto-/chemokine were tracked over a period of 11 days at 8 time points during 3 cycles of intravenous OT-101 therapy (140 mg/m2/day) for 12 PAC patients. A mixed ANCOVA model was developed to time evolution of 19 cyto-/chemokine levels with median expression 1 following OT-101 therapy. Pearson pairwise correlation coefficients of cyto-/chemokine levels across all time points and all patients were utilized to construct a correlation cluster to identify co-regulated cyto-/chemokines. Regression and hierarchical cluster analyses were performed to identify potential cytokine signatures. Protein-protein interaction networks were constructed using STRING10 algorithm. Plasma cyto-/chemokine levels were compared with OS outcome. Results: Three highly correlated subsets of cyto-/chemokines (Cluster 1: EGF, MIP-1α, MIP-1b; Cluster 2: FGF-2, IL-1R, MIG, IP-10, IL-15, IFN-α, IL-12A; Cluster 3: IL-2R, IL-6, IL-8, HGF) were identified following OT-101 therapy. An increasing trend was observed among 13 cytokines. 4 of the 12 patients exhibited a consistent increase in MIP-1α and IL-1b. Suppression of TGF-b signaling by OT-101 led to upregulation of IL-15, IP-10 and HGF. 3 significant associations of cyto-/chemokine and OS were observed at Cycle 1 measurements. The ANCOVA model that examined the levels of 31 cyto-/chemokines with OS as the co-variate resulted in IL-8 exhibiting a significant positive association with OS ( P= 0.0039). Conclusions: Levels of IL-8 were positively associated with OS across 12 PAC patients serving as potential biomarkers for treatment outcome following OT-101 therapy. Clinical trial information: NCT00844064.
Chemotherapy and survival benefit in elderly patients with advanced gastric cancer.
Authors: Sugimoto Aya , Nishida Tsutomu , Takahashi Kei , Mukai Kaori , Matsubara Tokuhiro , Hayashi Shiro , Yamamoto Masashi , Nakajima Sachiko , Fukui Koji , Inada Masami 
Published: March 2017

45 Background:There is little evidence if chemotherapy (CT) offer survival benefit for elderly patients (EP) with advanced gastric cancer (AGC). Methods: This was a single-centre retrospective study. A total of 118 patients with AGC were hospitalized at our hospital from April 2012 to June 2016. Of them, EP older than 75 years with AGC were eligible for inclusion in the study. Basically, the treatment strategy, chemotherapy (CT) or best supportive care (BSC) were comprehensively decided according to their background. We evaluate the risk factors for survival using the Cox proportional hazard model and explored the optimal indication for CT for EP. Results: Of 118 patients with AGC, 47 patients were enrolled as EP [63% men; mean age, 81 years]. Of EP, 26 patients (55%) received CT and 21 patients received BSC. As first-line CT, 13 patients received S1 monotherapy, the others treated with combination agents. The median overall survival time (MST) was 138 days. There was no significant difference between CT and BSC group (172 vs. 118 days, p = 0. 1087). Univariate analysis revealed the following 5 factors for poor prognosis were significant (defined as p-value < 0.1): Performance status (PS) 3a 2 (HR3.7, 95% CI: 1.5-8.5), C-reactive protein levels 3a 1mg/dL (HR4.0, 95% CI: 1.8-9.4), albumin level < 3g/dL (HR2.1, 95% CI: 1.1-4.3), neutrophil/lymphocyte ratio (NLR) 3a 4 (HR3.7, 95% CI: 1.7-8.5), and diffuse type (HR1.8, 95% CI: 0.9-3.8). As each poor risk factor of 5 and age factor 3a 80 years represents point 1, we calculated total points (0-6) for each patient. Median total points of CT and BSC were 2 and 4, respectively (p = 0.0196). Therefore, we set cut-off point of 3. Then, EP with a total point of 3 and more were classified as high risk group (HR: N = 25) and the others were as low risk group (LR: N = 22). There was significantly longer MST in LR than HR (all EP; 457 vs 105 days, HR: 0.23, p = 0.0002 and EP with CT; 232 vs 113 days, HR:0.26, p = 0.0085). Conclusions: Our findings using the scoring system including 6 factors suggest that EP with a total point 3 and more, were poor prognosis and may not receive benefit from CT for AGC. When judging indication for CT in EP with AGC, this scoring system may be useful, and in case of LR (total point 0-2) may be considered an indication for CT.
Small bowel adenocarcinoma treatment: A single centre experience.
Authors: Bredin Philip , McKendrick Joseph J , Cooray Prasad , Wong Rachel 
Published: March 2017

451 Background: Small bowel adenocarcinoma (SBA) has a high mortality. Randomised controlled trials are not feasible due to its rarity, therefore there is no gold standard treatment approach. Surgical resection for early stage disease is the only potentially curative option. Systemic therapeutic options are generally extrapolated from oesophagogastric and colorectal chemotherapy regimens. Methods: This is a retrospective review of treatment and outcomes for SBA patients who attended Eastern Health between 1st January 2010 and 30thJune 2015. Approval was obtained from the Eastern Health Human Research and Ethics Committee. Results: Thirty-six patients with SBA were identified: 16 (44%) duodenal, 12 (33%) ampullary, 6 (17%) jejunal, 2 (6%) terminal ileum, 1 not specified. Median age was 72 and 25 (69%) were male. Stage at diagnosis was as follows: Stage 1 = 4 (11%), Stage 2 = 8 (22%), Stage 3 = 9 (25%) and Stage 4 = 10 (28%). Surgery with curative intent occurred in 19 patients (Whipple’s = 13, wide local excision = 6) of whom 6 received adjuvant (predominantly fluoropyrimidine-based) chemotherapy. One patient died from post-operative complications. At last follow-up, 8 patients remained in complete remission; 11 had relapsed; 3 were lost to follow-up. Three patients had died due to disease. Median relapse-free survival in the curative-intent group was 21.4 months. Median overall survival (OS) has not been reached. Sixteen patients were initially treated with palliative intent. Ten underwent palliative surgery (bypass = 7; resection = 3). Overall, 16 patients commenced palliative chemotherapy, including 8 from the curative-intent group post-relapse. The most commonly used regimen was oxaliplatin plus fluoropyrimidine. Best responses to chemotherapy were partial response = 5 (31%) and stable disease = 4 (25%). Six patients received second-line chemotherapy. Median progression-free survival on first-line chemotherapy was 4.8 months. Median OS was 9.4 months. Conclusions: SBA has a poor prognosis. Although 56% of advanced SBA patients had disease control using chemotherapy extrapolated from other gastrointestinal malignancies, responses were not durable.
The effect of duloxetine on chemotherapy-induced peripheral neuropathy in advanced pancreatic cancer patients receiving gemcitabine plus nab-paclitaxel treatment.
Authors: Suzuki Hidetaka , Shinohara Akira , Ohno Izumi , Mitsunaga Shuichi , Takeno Misaki K , Funazaki Hideki , Kimura Gen , Watanabe Kazuo , Umemoto Kumiko , Sasaki Mitsuhito , Takahashi Hideaki , Imaoka Hiroshi , Hashimoto Yusuke , Ikeda Masafumi , Yamaguchi Masakazu 
Published: March 2017

453 Background: Recently, gemcitabine plus nab-paclitaxel (GN) has come to be used frequently as the first-line chemotherapy for advanced pancreatic cancer. It has been reported that chemotherapy-induced peripheral neuropathy (CIPN) associated with nab-paclitaxel (nab-PTX) may impair the quality of life of the patients, and may, moreover, necessitate dose reduction or early cessation of the chemotherapy, thereby potentially impacting patient survival. However, there are no established treatments against CIPN. Several reports have suggested that duloxetine, which has been proved to be highly effective in managing diabetic peripheral neuropathy, is also effective against CIPN induced by platinum agents and taxanes. The aim of this study was to examine the frequency of nab-PTX related CIPN, its various influences, and the efficacy of duloxetine in the management of CIPN. Methods: Data of 121 pancreatic cancer patients who received GN as first chemotherapy between December 2014 and December 2015 at the National Cancer Center Hospital East, Japan, were analyzed retrospectively. Results: The frequency of CIPN of any grade was 60.3% (73 patients) and that of CIPN of grade ≥ 2 was 21.5% (26 patients). Among the patients who showed CIPN, 34 patients received 20-60 mg of duloxetine once daily, and the remaining patients never received it (no duloxetine group). 18 patients were on duloxetine for more than four weeks (the duloxetine group). 8 patients discontinued duloxetine in less than four weeks because of its side effects, such as, nausea, and somnolence. In the duloxetine group, CIPN was improved in 4 patients, and remained non-progressive in 12 patients. The relative dose intensity (RDI) of nab-PTX since the emergence of CIPN in the duloxetine group was higher than that in the no duloxetine group (63.2 % vs. 48.2 %, p = 0.0046). Conclusions: The frequency of nab-PTX related CIPN at our hospital was almost similar to that of previous reports. The results of this study suggest the possibility that duloxetine not only improves nab-PTX-related CIPN, but delays its progression. Therefore, it might contribute to continuing GN with a high RDI for longer periods of time.
Surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: Meta-analysis of randomized controlled trials.
Authors: Lee Kyung-Hun , Lee Dae-Won , Jang Myoung-Jin , Kim Tae-Yong , Han Sae-Won , Oh Do-Youn , Im Seock-Ah , Kim Tae-You 
Published: March 2017

454 Background: Time to progression (TTP) is suggested as a reliable endpoint compared to progression free survival (PFS) in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied. Methods: We searched Pubmed and Embase data to obtain data source. Eligible studies were randomized controlled phase III trials which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association of treatment effects as shown by the hazard ratio (HR) of TTP and OS in each trial was assessed by Spearman rank correlation coefficient ( rs) and linear regression analysis. The association between median TTP and OS was also investigated. Results: Nine studies with a total of 18 treatment arms and 6318 patients were included. Incremental benefit from the study treatment in TTP from each trial was correlated with incremental benefit in OS. The rs value and R2 value between log (HRTTP) and log (HROS) was 0.73 (95% CI 0.12 – 0.94, p = 0.024) and 0.57. The minimum TTP effect to predict a treatment effect on OS was 0.63. Median TTP was associated with median OS. The rs value between TTP and OS was 0.73 (95% confidence interval (CI) 0.40 – 0.89, p < 0.001) and the corresponding R2 was 0.42. Conclusions: Our study results suggest that TTP could be used as a surrogate marker for OS in the clinical trials of advanced HCC. However, the results suggest modest correlation between treatment effects on TTP and OS. Along with individual-level analysis more evidences are needed to confirm our finding.
Can total psoas area predict toxicity after stereotactic body radiation therapy in borderline resectable and locally advanced pancreatic cancers?
Authors: Jin Will , Mellon Eric , Frakes Jessica M. , Murimwa Gilbert , Hodul Pamela Joy , Pimiento Jose Mario , Soares Heloisa P. , Kim Richard D. , Malafa Mokenge Peter , Hoffe Sarah E. 
Published: March 2017

455 Background: Total Psoas Area (TPA), a marker of sarcopenia, found clinical utility as an independent predictor of clinical outcomes in gastrointestinal cancers as a proxy for nutritional status. Our study evaluated the relationship of TPA and other proxies of nutrition like Body Mass Index (BMI) and Body Surface Area (BSA) with outcomes in Borderline Resectable Pancreatic Cancer (BRPC) and Locally Advanced Pancreatic Cancer (LAPC) patients receiving Stereotactic Body Radiation Therapy (SBRT). Methods: In retrospective analysis of an IRB approved database, 183 BRPC and LAPC patients treated with SBRT from 2009-2016 met our selection criteria. Patients underwent gemcitabine based or FOLFIRINOX chemotherapy for 3 months prior to SBRT. Eligible patients were those with pre-SBRT planning CT imaging on Pinnacle, a treatment planning system, and an identifiable L4 vertebra. Bilateral psoas muscles were manually contoured at the L4 vertebral level. This area was normalized by patient height (median = 876.505 mm2/m). ROC curves were created for TPA, BMI and BSA. Toxicities were evaluated by binomial logistic regression; survival functions were evaluated by Kaplan-Meier. Significance was set at p < 0.05. Results: Low TPA (OR = 1.903, p = 0.036) and BSA (OR = 1.836 p = 0.048) were predictive of acute toxicities but only TPA was predictive of Grade 3+ acute toxicities (OR = 10.24, p = 0.040). Both findings were independent of tumor resectability. No association was found between TPA/BMI/BSA and late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median = 21.98 months) than their LAPC (median = 16.2 months) counterparts (p = 0.002), independent of nutritional status. Conclusions: Pre-SBRT TPA measurement is readily available and more specific than BMI or BSA as a predictor of serious acute radiotoxic complications following SBRT in BRPC/LAPC patients. However, tumor resectability remains as the only predictor of overall survival in this cohort. Whether initial pre-chemo TPA may predict acute toxicity related to chemotherapy and guide individualization of systemic regimen warrants further investigation.
Clinical outcomes of early-stage ampullary carcinoma: A single institutional experience.
Authors: Manne Ashish , Reddy Sushanth , Li Peng , Contreras Carlo M. , Christein John , Vickers Selwyn M. , Heslin Martin , Jacob Rojymon , Wang Thomas N. , Kasi Anup , Posey James , Paluri Ravi Kumar 
Published: March 2017

456 Background: Ampullary carcinoma [AC] is a rare malignancy associated with favorable prognosis among pancreatobiliary tumors. Pancreaticoduodenectomy [PDY] is considered to be curative for early stage cancers. The role of adjuvant chemotherapy [CT] or combination chemoradiation [CRT] remains uncertain for stage I/II. In this analysis we reviewed our institution’s experience with AC. Methods: From 2005 to 2015, 62 patients with stage 1 and 2 AC with at least one year follow up after PDY were reviewed. Clinical and pathologic factors and disease status were obtained from chart review. The patients’ demographical and oncological characteristics are summarized. The univariate Cox proportional hazard model was conducted for evaluating the parameters associated with overall survival. Kaplan-Meier method and log-rank was used to compare the time-to-events. Results: Adjuvant treatment was administered in 61%: CT (32%), CRT (29%) 39% surgical alone. The median overall survival [OS] for the study cohort is 60 months with 3 yr OS at 58% and 5 yr OS at 50%. Recurrence noted in 21% of patients. About half of patients surviving five years were alive at 10 years. Lymph node [LN] metastases (57%) predicted worse PFS (HR 2.29, 95% CI (1.13-4.61), p = 0.021) but did not significantly affect OS (HR 1.2, 95% CI (0.84-3.61);p = 0.13). There were no postoperative deaths following surgery.Peri- pancreatic extension [PPE] (20%) and peri-neural invasion [PNI] (16%) was also found to be determinants for poor OS. Current data did not suggest lympho-vascular invasion (24%) predict OS (HR 1.20, 95% CI (0.49, 2.96);p = 0.63 or PFS(HR 1.45 (0.65, 3.20),p = 0.36). When compared to surgery alone adjuvant CT or CRT had no statistically significant difference in terms of PFS (p = 0.53) or OS (p = 0.96). Conclusions: The use of adjuvant treatment may be most useful at improving long-term disease control in patients with high-risk features; however, no significant difference between CT and CRT was demonstrated in our series. This could be due to small sample size and needs further validation in larger cohort. PDY with regional lymphadenectomy is appropriate for early-stage AC, but worst outcomes seen in patients with PPE, PNI and LN involvement.
Analysis of outcomes in metastatic pancreatic cancer: Real-world experience in academic cancer centers.
Authors: Popa Elizabeta C. , Rabinovich Emma , Sohal Davendra , Arbour Kathryn Cecilia , Kim Timothy Suyong , Lu Yao , Christos Paul J. , Khorana Alok A. , Shah Manish A. 
Published: March 2017

458 Background: FOLFIRINOX is an active regimen for metastatic pancreatic cancer demonstrating a median overall survival of 11.1 months at the expense of significant treatment-related toxicity. Dose modifications are routinely used in clinical practice however there is little data regarding impact on outcomes and use of second line therapy. In this study we report on the treatment course and outcomes of 92 patients treated at two academic centers. Methods: We conducted an IRB-approved retrospective cohort study of patients with metastatic pancreatic adenocarcinoma treated with first line FOLFIRINOX between 2011 and 2015. Hazard ratios were calculated by Cox proportional hazard models and median survival was estimated using Kaplan-Meier method. Results: 92 patients were identified with a median follow-up of 13.2 months (range 1.2-47.3 mo); 57 males (62%), ECOG 0/1 = 75 (82%). Fifty-four percent required dose reductions of >25% in at least one of three component drugs within the first 6 cycles [95% CI 0.44, 0.65]. Irinotecan was dose reduced in 43% of patients (n=39) while 64% required modification or discontinuation of 5FU. Ten patients (11%) received the full dose of FOLFIRINOX as originally published and 17 patients (25%) discontinued FOLFIRINOX due to toxicity. 60% of patients demonstrated disease control at first imaging assessment after 4-6 cycles of treatment. Median PFS was 7.11 months (95% CI: 5.06-8.51) and OS 13.01 months (95% CI: 9.17-16.95). There was a decrease in PFS and OS associated with a dose reduction of two or more drugs with a HR of 1.68 (95% CI 1.01-2.82, p=0.048) and 1.98 (95% CI 1.08-3.65, p=0.027) respectively. Sixty-seven patients [73%] went on to receive 2nd line therapy [n=67] with 55% receiving gemcitabine-based regimens, the majority with nab-paclitaxel [82%]. Forty-two patients demonstrated progressive disease [63%]. Conclusions: Modest FOLFIRINOX dose modifications are prevalent in clinical practice and are not associated with a reduction in efficacy. A median survival of 13 months with dose modified FOLFIRINOX is compelling. Dose reduction of 2 or more agents was associated with diminished survival. Second line therapy following FOLFIRINOX was associated with modest activity.
FDG PET/CT in pancreatic cancer staging and management: A retrospective study.
Authors: Kinupe Abrahao Ana Beatriz , Ung Yee , Ko Yoo-Joung , Berry Scott R. 
Published: March 2017

464 Background: FDG PET/CT scan (PET) has been approved by Cancer Care Ontario since 2011 for pancreatic cancer patients who have potentially resectable disease. A recent prospective study supported the use of PET in patients with a pancreatic mass and showed improved staging accuracy. Herein, we reviewed the outcomes of PET in the disease staging and management of patients with pancreatic mass at a single academic center. Methods: We collected demographics, CA 19-9 level, CT, MRI and PET results of patients with suspicious pancreas mass followed at Sunnybrook Health Sciences Centre from April to August 2011. We reviewed disease staging after CT/MRI and clinical management decision after PET result. We excluded patients with proven non-primary adenocarcinoma of the pancreas from the analysis. Results: In this cohort, 58 patients had PET scans. 14 patients with non-primary adenocarcinoma of the pancreas were excluded. From 44 patients analyzed, 61% of them were females, median age 70, 19 patients had biliary obstruction with biliary drain, CA 19.9 was elevated preoperatively in 27 patients (level above 1400 was seen in 37% of 44 patients), pancreatic mass median SUV = 4.8 and 7 patients had SUV < 2.5 with no FDG avid at the pancreas mass (both biopsy proven). Ten patients were discovered to have metastatic disease on PET. PET results were discordant with the CT/MRI disease staging in 34% of cases. PET revealed metastatic disease in 7 patients with prior CT or MRI considered to be negative for metastasis. PET showed localized disease in 8 patients with suspicious metastasis on CT or MRI. However, none of the patients underwent pancreatic resection. Clinical management was changed after PET results in 80% of patients with discordant PET and CT/MRI results. Conclusions: In this single-centre retrospective analysis, PET results changed the metastatic disease status depicted by CT or MRI in 34% of patients and clinical management was guided by PET results for the majority of those patients. This supports the use of PET as a tool to guide staging and treatment of pancreas cancer.