bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localized pancreatic cancer (LPC) with isolated positive peritoneal cytology (PPC): A single-institution experience.
Authors: Oh Stephen Y , Edwards Alicia M , Hahn Hejin P , Mandelson Margaret T , Picozzi Vincent J. 
Published: February 2017

411 Background: Natural history (NHx) and overall survival (OS) of patients (pts) with LPC and PPC without gross metastasis (GM) at initial diagnosis are rarely studied. We assessed rate, time and pattern of disease recurrence (REC), impact of local therapy (Rx) and OS in this pt cohort from our institution. Methods: The Virginia Mason Pancreatic Cancer (PC) Database (Picozzi et.al. Proc GI Cancer Symp 2011) was used to identify pt cohort. Inclusion criteria were 1) laparoscopic PPC and 2) no other evidence of GM (radiographic/ laparoscopic). Local progression (LP) was defined as primary tumor growth with change/cessation of chemoRx. Systemic progression (SP) was defined as radiological/pathological metastastic progression. The database provided OS. Results: 39/884 (4.4%) pts initiating Rx at VMMC from 2003-2014 met these criteria. 13/39 pts were included in a prior report (Clark et.al. Am J Surg 2010). Pt characteristics include: 21/39 (54%) male; median (med) age 65 (range 49 – 83) yrs; 25/39 (64%) head lesions; med tumor size 39 (range 25 - 100) mm. Med pt follow-up is 13 mo. All pts received gemcitabine-combination chemoRx as initial Rx. 14/39 (36%) pts also received local Rx (13 consolidative chemoXRT, 1 surgery). 3 month (mo) disease control (DC) was 86% (31/36 pts, 3 pts followed <3 mo). 6 mo progression - free survival (PFS) was 72% (26/36 pts). 6/36 pts (16%, range 9+-15+ mo) are progression – free. 30/36 pts (83%) progressed (med time 8.1 mo). REC pattern was local (13/30 pts, 43%), distant (9/30 pts, 30%) and combined (8/30 pts, 27%). Pts given local Rx did not differ statistically from pts given systemic Rx only with respect to 3 mo DC, 6 mo PFS, REC rate, time, or pattern, or OS. OS for LPC with PPC was significantly better than pts with GM (n = 277) identified from the database from 2003-2014 (med OS 15 vs. 9.3 mo, p = 0.0002; 1-yr OS 68 vs. 32%, p = 0.01; 2-yr OS 34 vs. 12%, p = 0.007). Conclusions: 1)LPC with PPC is a rare PC pt cohort with high response rates to chemoRx and superior OS to those with GM. 2) However, long-term disease free OS was not seen. 3)Local Rx did not clearly alter pt cohort NHx. 4)This is the largest pt series of this pt cohort compiled from a US institution; their further study seems of value.
Adjuvant treatment patterns and clinical outcomes in patients with curative resected ampulla of Vater cancer.
Authors: Ha Hyerim , Oh Do-Youn , Kim Tae-Yong , Lee KyoungBun , Kim Kyubo , Lee Kyung-Hun , Han Sae-Won , Chie Eui Kyu , Jang Jin-Young , Im Seock-Ah , Kim Tae-You , Kim Sun-Whe , Ha Sung Whan , Bang Yung-Jue 
Published: February 2017

415 Background: Ampulla of Vater cancer (AoV ca) is rare tumor, and its adjuvant treatment after curative resection has not been well established. The purpose of this study is to see the clinical outcomes of curatively resected AoV ca patients and to figure out the role of adjuvant treatment. Methods: We reviewed 227 AoV ca patients who underwent curative resection at the Seoul National University Hospital between 1997 and 2012. Clinical factors, pathologic findings, adjuvant treatment pattern, disease-free survival (DFS) and overall survival (OS) were analyzed. Results: Median age was 61.5 year old (range, 33.8-88.2) and 125 patients were male. T1/T2 stage was found in 63.9% of patients and T3/4 stage was in 36.1%. Seventy-seven patients (33.9%) had node positive disease (N+) and seventy-three patients (32.1%) had well-differentiated histology. OS of all patients was 90.9 months (95% CI: 58.4-128.09). 5-Year OS- and DFS- rate were 58.2% and 62.5%, respectively. On multivariate analysis, adverse prognostic factors for OS included poorly differentiated histology (HR 1.35, 95% CI: 1.01-1.81, p=0.045), elevated CEA (HR 2.55, 95% CI: 1.29-5.04, p=0.007), elevated CA 19-9(HR 1.86, 95% CI: 1.08-3.21, p=0.027), and stage (HR 2.34, 95% CI: 1.43-3.82, p=0.001). A total of 104 patients (46.3%) received adjuvant treatment (concurrent chemoradiotherapy (CCRT) 32, CCRT with maintenance chemotherapy 58, chemotherapy alone 9, radiotherapy alone 5). Most of the chemotherapies were 5-FU-based ones. Among patients with T1/T2 & N (-) (n=111), only 25 patients (22.5%) received adjuvant treatment. In contrast, among patients with T3/T4 or N (+) (n=116), 79 patients (68.1%) received adjuvant treatment. 5Y-OS rate was 74.1% in patients with T1/T2 and N (-) and that of patients with T3/T4 or N (+) was 43.0% (p<0.001). In T1/T2 and N (-) stage, OS was not different according to adjuvant treatment. In T3/T4 or N (+) stage, adjuvant CCRT with maintenance chemotherapy conferred the longest OS, which was not statistically significant. (5Y-OSR: 47.0% vs 41.4% in no adjuvant treatment.) Conclusions: Adjuvant treatment should be further defined in AoV ca, especially in T3/T4 or N (+) stage.
Effect of complications after pancreaticoduodenectomy on adjuvant therapy utilization and survival in pancreatic cancer.
Authors: Hnoosh Dima , Saeed Hayder M. , Huang Bin , Maynard Erin , Durbin Eric B , DeSimone Philip A. , Kudrimoti Mahesh R. , Anthony Lowell Brian , Hosein Peter Joel , McGrath Patrick , Tzeng Ching-Wei David 
Published: February 2017

422 Background: While adjuvant therapy (AT) completion is a necessary component of multimodality therapy for pancreatic adenocarcinoma (PDAC), its timing and utilization can be hindered by complications after pancreaticoduodenectomy (PD). The primary aim of this study was to evaluate the impact of post-PD complications on AT utilization and overall survival (OS). Methods: Patients treated with PD for PDAC at a single institution (2000-2012) were evaluated. Data on 90-day complications were extracted from the electronic medical record with postoperative major complications (PMC) defined as Grade ≥3. Patient records were linked to the Surveillance Epidemiology End Results - Kentucky Cancer Registry for AT and OS data. Early AT required a first dose before 8 weeks, while late was 8-16 weeks. Initiation after 16 weeks was not considered adjuvant. Chi-square statistics, Kaplan-Meier plots, and log-rank tests were used to examine associations among complication status and AT timing, AT utilization, and OS. Results: Of 84 total patients, 54 (64%) received AT (34 [41%] early; 20 [24%] late). Rates of patients with 90-day complications were as follows: 44 (52%) Grade ≥1, 37 (44%) Grade ≥2, and 18 (21%) Grade ≥3. Low-grade (Grades 1-2) complications were not associated with late AT or lack of AT (both p>0.082). However, PMC were associated with lower rates of AT (7/18, 39% with PMC vs. 47/66, 71% without PMC, p=0.011). Even patients who recovered from PMC were less likely to meet the early 8-week window (4/18, 22%, patients with PMC, vs. 30/66, 46%, patients with no PMC, p=0.039). PMC were associated with worse median OS (6.1 mo, 95% confidence interval, CI, 1.6-12.1, vs. 20.8 mo, 95% CI 17.3-23.8, with no PMC, p<0.001), while low-grade complications were not (all p>0.079). Conclusions: In this series,low-grade complications had minimal effects on AT timing, AT utilization, and OS, but PMC were associated with late and decreased AT utilization and negatively impacted OS.These data suggest that strategies to decrease PMC and/or treatment sequencing alternatives to increase multimodality completion rates in high-risk patients may improve oncologic outcomes.
Triptolide to induce cell death of pancreatic cancer cells via inhibition of 14-3-3γ expression.
Authors: Wang Wei , Luo Jinbing , Liang Yinghui , Chen Yubin , Lin Wenjie 
Published: February 2017

425 Background: Pancreatic cancer is one of the malignant tumors which exhibit resistance to chemotherapy. Gemcitabine-based therapy is a standard for advanced pancreatic cancer though it brings severe side-effect and average median survival is only 6 months. Hence increasing interest has focused on new agent with targeted therapies. Here we investigated the growth-inhibitory and apoptotic effect of triptolide, a diterpenoid triepoxide, and the role of 14-3-3γ expression in the apoptotic pathway induced by triptolide in human pancreatic cancer cells (AsPC-1 and PANC-1). Methods: Cell proliferation was measured by SRB, apoptotic cells were assessed by flow cytometry for Annexin V/PI staining and western blot for cleaved caspase-8, 9, 3 and fluorescent substrate assay for activities of caspase-8, 9, 3. To explore further mechanism of triptolide triggering death receptor pathway, specific siRNA targeted for 14-3-3γ was used to knock down 14-3-3γ expression measured by ELISA. In vivo, AsPC-1 xenografts in the absence or presence of stable down-regulation of 14-3-3γ expression by RNAi were treated with triptolide for 4 weeks and the tumor growth was compared, tumor samples were tested by ELISA and western blot for 14-3-3γ level. Results: Triptolide inhibits the proliferation at extremely low concentrations (12.5-50 nM) and induces apoptosis of pancreatic cancer cells through activating the caspase cascade associated with Bid cleavage. Moreover triptolide inhibited 14-3-3γ expression at dose and time-dependent manner and 14-3-3γ down-regulation sensitized cells to triptolide-induced apoptosis. Likewise, in vivo experiment of AsPC-1 xenografts, stable down-regulation of 14-3-3γ expression by RNAi significantly enhances triptolide-induced apoptosis and tumor growth delay. Conclusions: Triptolide exerted significant growth inhibitory effects and induced apoptosis in vitro and in vivo. Triptolide may have a potential to be an effective agent against pancreatic cancer and its mechanism of action is mediated by the inhibition of 14-3-3γ expression. The role of 14-3-3γ expression involved in resistance to apoptosis pathway make it be a potential therapeutic target in pancreatic cancer.
Laboratory evaluation of hepatic synthetic function as a predictor of ethiodol retention during transarterial (chemo) embolization in hepatocellular carcinoma (HCC).
Authors: Dyer Brandon Alan , McCallum Raluca , Savitsky Leah , Kato Catherine , Fuss Martin , Thomas Charles R. , Naugler Wilscott , Kolbeck Kenneth , Kaufman John , Farsad Khashayar , Fung Alice , Tanyi James 
Published: February 2017

431 Background: Image-guidance for HCC suffers due to a lack of contrast between tumor and liver parenchyma. To compensate for the inability to directly visualize the radiation target other IGRT strategies have been employed for target optimization. Transarterial embolization (TAE) and transarterial chemoembolization (TACE) are level 1, evidence-based treatments for HCC and improve survival by several months; however, local failure occurs in up to 50% of treated lesions by 6 months. The lack of durable local control provides a rationale to add a second treatment modality. If Ethiodol is used as an embolizing agent, the treated HCC becomes radio-opaque. In the current assessment, we correlated the quality of Ethiodol tumor stains with liver function parameters as prognosticators for Ethiodol stain retention prior to simulation for SBRT. Methods: Records of 31 patients undergoing staged TAE/TACE prior to SBRT (50 Gy/5) were evaluated under an institutional protocol. The quality of Ethiodol stains in simulation CT were graded as excellent (mean HU of >300), good (mean HU of 225-300), fair (mean HU 150-225), and poor (mean HU <150). A liver function panel, general labs, Child-Pugh and MELD scores prior to TACE/TAE were also recorded and correlated with the quality of Ethoidol stain at simulation. Results: Duration between TACE/TAE and simulation was 124+120 days. Simulation scans showed excellent, good, fair and poor tumor stains in 7 (mean HU =360+48), 3 (mean HU =262+17), 15 (mean HU =184+24) and 6 (mean HU =130+16) cases, respectively. Of all laboratory testing, only Child-Pugh score showed strong statistical correlation (p<0.0012) with the retention of Etioldol. Conclusions: TACE/TAE-based Ethiodol tumor stain facilitates tumor visualization for SBRT of HCC. While it is not conclusive that laboratory testing can serve as a predictor of Ethiodol stain retention between TACE/TAE and simulation for SBRT, the Child-Pugh score presents a unique matrix for patient stratification.
The referential survival data of borderline resectable pancreatic cancer (BRPC) patients who are candidate for neoajuvant chemotherapy followed by surgery.
Authors: Saito Kei , Ishii Hiroshi , Ozaka Masato , Osumi Hiroki , Yamada Ikuhiro , Sasaki Takashi , Matsuyama Masato , Takano Kouichi , Sasahira Naoki 
Published: February 2017

434 Background: The aim of this study is to clarify referential survival data of BRPC patients who are candidate for neoajuvant chemotherapy followed by surgery. Methods: This retrospective study included data from all consecutive patients who were diagnosed as having invasive ductal pancreatic cancer at our hospital between January 2008 and December 2013. Selection criteria were as follows: patients who 1) had histologically confirmed pancreatic adenocarcinoma, 2) were diagnosed as having non-metastatic disease by dynamic CT before treatment, 3) had received anti-cancer treatment, and had been observed for 3 months or longer. We reviewed CT stage (UICC) and treatment modality, and analyzed their survival data. Results: There were 428 patients who met the selection criteria. Among them, clinical CT stage I/II (Group A; potentially respectable) and stage III (Group B; locally advanced) were documented in 170 (40%) and 131, respectively. Laparotomy was performed in all patients in Group A. Of the 170 in Group A, 166 (98%) received resection with curative intent, and the remaining 4 did not received resection because of discovery of occult metastasis at laparotomy. Of the 131 in Group B, 36 (27%; Group B-1) received resection with curative intent, 7 did not received resection because of occult metastasis, and the remaining 88 did not receive laparotomy because they were diagnosed as having locally advanced unresectable disease by CT. Among Group B, patients other than Group B-1 received gemcitabine-based chemotherapy (Group B-2; N=95). The median survival time, 1-yr, 2-yr, and 3-yr survival rate were 28.7 months, 78.6%, 55.5%, and 38.9% in Group A, 16.8 months, 63.8%, 31.8%, and 19.8% in Group B-1, and 13.8 months, 60.1%, 21.7%, and 5.9% in Group B-2, respectively. Conclusions: Based on our historical data, we suppose that 16.8 months of median survival time or survival rate of 19.8 at 3-yr, i.e, Group B-1 survival data, may be an appropriate threshold value in the single-arm phase 2 BRPC study.
Outcomes and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma (HCC).
Authors: Ziogas Dimitrios , Thillai Kiruthikah , Korantzis Ippokratis , Chowdhury MH Ruhe , Papadatos-Pastos Dionysios , Suddle Abid , O'Grady John , Heaton Nigel , Ross Paul J. , Sarker Debashis 
Published: February 2017

435 Background: HCC is the third commonest malignancy worldwide, with the highest incidence rates in patients over 75 years of age. Although sorafenib is used for patients with advanced HCC, there are concerns about the outcomes and tolerability in this age group. Methods: We conducted a retrospective study of 190 patients treated with sorafenib (177 with sorafenib alone, 17 patients with a combination of sorafenib and erlotinib/placebo within the SEARCH trial). Patient demographics and outcomes were recorded. Results: 190 patients were identified with a median age of 66 (26-87). 151 patients were <75 years old (yrs) and 39 patients were >75. 157 patients were male and 33 female. Underlying liver disease in the over 75 group were: non-alcoholic fatty liver disease (N=14, 35.9%), unknown aetiology (N=14, 35.9%), alcoholic liver disease (N=7, 17.9%), hepatitis C (N=2, 5.1%), hepatitis B (N=1, 2.56%,) and autoimmune hepatitis (N=1, 2.56%). 33 patients were Child-Pugh A status when starting sorafenib (A5=25, A6=8) and 6 patients were Child-Pugh B (B7=5, B8=1). There was no statistically significant difference in OS between patients over the age of 75 and younger (7.1m for >75 yrs and 10.4 <75 yrs p=0.360), or in PFS (4.2m vs. 6.8m [p=0.539]). There was also no increase in G3/4 toxicities between both groups of patients with comparable incidences of G3/4 diarrhoea (4.7% <75 vs. 2.6% ≤75 p=0.481), skin toxicity (6.6% vs. 5.1% p=0.537), fatigue (7.3% vs. 7.7% p =0.58) and deteriorating liver function (2.6% vs. 7.3% p = 0.25). There was no difference between the incidence of dose reductions or interruptions (34% vs. 35.9% p=0.5). Conclusions: Our study suggests that patients aged 75 or older appear to tolerate treatment with sorafenib well with comparable toxicities to those less than 75. We also found no significant differences in survival. With an aging population and increasing incidences of HCC, further prospective evidence is needed to identify safety and survival outcomes in this important group of patients.
FOLFIRINOX chemotherapy in locally advanced and metastatic pancreatic adenocarcinoma: A retrospective analysis of toxicity and outcomes.
Authors: Kerr Ashleigh , Grose Derek B , Hall Sally , McIntosh David , MacLaren Vivienne , Ali Clinton , Hennessy Aisling , McDonald Alexander , Graham Janet Shirley 
Published: February 2017

436 Background: The FOLFIRINOX chemotherapy regimen has been shown to improve overall survival in patients with metastatic pancreatic cancer, however, toxicity is increased. The aim of this analysis was to assess the tolerability and outcomes of this regimen in clinical practice. Methods: A retrospective analysis of patients treated with FOLFIRINOX chemotherapy in a tertiary referral centre between January 2013 and May 2014 was conducted. Toxicity was graded as per CTCAE version 4.0. Overall survival and tumour response were analysed. Results: A total of 80 patients were identified with locally advanced or metastatic disease in 47 and 33 cases respectively. The median patient age was 63 (range 30 –79) and the median number of cycles delivered was 6 (range 1-12). G3/4 neutropenia was recorded in 12.5% of patients, with a febrile neutropenia rate of 9.9%. G3/4 nausea and vomiting was reported in 17.5% and G3/4 diarrhoea in 15% of cases. G3/4 electrolyte disturbance occurred in 5%. Response rates assessed after 3-6 cycles showed PR 26%, SD 31% and PD 25%. Median duration of follow up for survivors is 8.7 months (range 3.6 – 20.8). Median OS is 11.4 months (95% CI 10.1 – 12.7). Median OS was reported as 11.4 months, 10.9 months and 2.3 months according to baseline PS 0, 1 and 2 respectively (log rank p <0.001). Conclusions: FOLFIRINOX can be safely delivered out with a trial cohort. Outcomes are strongly influenced by patient PS and careful patient selection is critical.
Phase I/II study of sorafenib in combination with intermittent hepatic arterial infusion chemotherapy using cisplatin for unresectable advanced hepatocellular carcinoma with portal vein tumor thrombus.
Authors: Ishizaki Morihiko 
Published: February 2017

441 Background: Our purpose in the study was to ascertain the feasibility of a combination therapy with sorafenib and hepatic arterial infusion therapy (HAIC) using cisplatin (CDDP) for unresectable advanced HCC included portal vein tumor thrombus. Methods: Phase I study: Soraenib was administered continuously, whereas CDDP was given on day1, 8, and 15. The dose of sorafenib was escalated in two steps from 400 to 800 mg/body, whereas the dose of CDDP was escalated in three steps from 20 to 25 and 30 mg/m2. We estimate the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of this therapy, to determine the recommended dose (RD). Phase II study: Thirty-five patients with unresectable HCC received this therapy under RD, and the efficacy and safety were assessed. Results: Phase I study: 15 patients (11 male/4 female, median age: 73.1 years) with unresectable advanced HCC have been enrolled. None of the patients treated with sorafenib 400mg and cisplatin 20 mg/m2 experienced DLT. Three of three patients treatd with sorafenib 800mg and cisplatin 20 mg/m2 experienced DLTs (two serum bilirubin elevation and one hepatic encephalopathy). None of the patients treated with sorafenib 400mg and cisplatin 25 mg/m2 experienced DLT. One of six patients treated with sorafenib 400mg and cisplatin 30 mg/m2 experienced dose-limiting thrombocytopenia, and One of them experienced dose-limiting serum aspartate aminotransferase elevation. Phase II study: 35 patients (27 male / 8 female, median age : 69.2 years) with unresectable advanced HCC have been enrolled. The clinical response were rated as 9 partial response (PR), 18 stable disease (SD), and 8 progressive disease (PD). Conclusions: In this study, RD of this therapy was sorafenib 400mg/body and CDDP 30 mg/m2. Sorafenib in combination with intermittent HAIC using CDDP for unresectable advanced HCC was expected to be safe and effective treatment. Clinical trial information: 000008571.
Role of neoadjuvant treatment regimens for locally advanced pancreatic cancer.
Authors: Alfayez Mohammad , Graham Janet Shirley , Hall Sally , McIntosh David , MacLaren Vivienne , McDonald Alexander , Ali Clinton , Hennessy Aisling , Karteszi Hedvig , Jamieson Nigel , Carter Ross , McKay Colin , Dickson Euan , Grose Derek B 
Published: February 2017

444 Background: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality worldwide. Lymph node involvement and resection margin status play important roles in predicting relapse. Resectable disease occurs in only 15–20% of total patients who present with PDAC. Unfortunately, margin involvement (R1) occurs in 70–80% of these patients. Emerging evidence has shown that the use of neoadjuvant chemotherapy and localised radiotherapy to downsize the tumours and increase the margin clearance (R0) rate may improve the overall survival of PDAC patients.We report a neoadjuvant therapy approach in the non-clinical trial setting of our large, tertiary cancer centre. Methods: We prospectively collected the outcome data and toxicity of 53 patients diagnosed with borderline resectable or initially non-resectable PDAC between 2012 and 2014. These patients received either FOLFIRINOX (FFX) or Gemcitabine/Capecitabine (GemCap) combination chemotherapies. Following restaging by computed tomography (CT), the patients proceeded to preo-operative 5-FU-based chemo-radiotherapy, immediate resection or subsequent palliativetherapies. Results: The median age was 65 (range 30 – 79) at PDAC diagnosis. Sixty-one percent (n=32) were male with the commonest anatomical location being the head of the pancreas (58%, n=31). The median follow up for survivors is 13.7 months (range: 5.3–24.4). The median overall survival was 18.3 months (95%, CI: 12.0–24.5). There was no statistical difference between overall survival in patients receiving FFX and GemCap chemotherapies. The margin clearance rate (R0) was 36% (4/11) in patients who proceeded to resection after neoadjuvant chemotherapy alone. The rate was 100% (4/4) in patients who received additional chemoradiation prior to surgery. Conclusions: This case series reveals that neoadjuvant therapy improved survival of patients with PDAC. In addition, we showed an increase in the R0 resection rate in patients who underwent chemoradiation prior to surgery. Further work is ongoing but based on historical data we believe that this neoadjuvant approach may lead to a long term survival benefit.