bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in clinical characteristics and treatment in hepatocellular carcinoma between Asians and non-Asians.
Authors: Wong Kit Man , Lee Jonghun John , Wong Amy , Liu Geoffrey , Sherman Morris , Cleary Sean P. , Knox Jennifer J. 
Published: February 2017

289 Background: Studies have demonstrated clinical differences in hepatocellular carcinoma (HCC) between Asians (AS) and non-Asians (NAS). In the US, AS are less likely to undergo liver transplant compared to Caucasians. Despite the large immigrant population in Canada, there has been no prior comparison of HCC in AS and NAS in the context of the Canadian universal health care system. We retrospectively evaluated the ethnic differences in HCC at the largest cancer centre in Canada. Methods: We analyzed 268 patients who enrolled in a Genetic Epidemiology Study of HCC (April 2010 to February 2013), where patients were asked to complete a questionnaire and give a blood sample at their first visit. Relevant clinical data were extracted and analyzed by descriptive statistics, t-test or Chi-square test. Results: The study population had a mean age of 61 years and 83% males. There were 45% AS, 49% Caucasians, and 6% other ethnicities. Etiologies of HCC included: Hepatitis B (HBV) 34%, Hepatitis C (HCV) 32%, non-alcoholic steatohepatitis 15%, alcohol 18%. Compared to NAS, HCC patients of Asian ancestry had significantly higher rates of HBV (60% vs. 12%, p<0.001). At diagnosis, 83% of patients were Child-Pugh A (mean MELD score 9.2). Ethnicity had no impact on Child-Pugh class, multifocal disease or macrovascular invasion. However, MELD scores were lower in AS (p=0.02). Overall, 71% of cases were initially treated with curative intent. Patients underwent various treatment modalities: liver transplant 13%, resection 31%, radiofrequency ablation 39%, transarterial chemoembolization (TACE) 21%, radiation 17%, systemic therapy 27%. AS had higher resection rates (41% vs. 22%, p<0.001), while no differences were observed for other treatments. Duration of response was 11.7 months for TACE (AS 14.2, NAS 10.5), 7.5 months for sorafenib (AS 6.8, NAS 8.1). Rate of intolerance to sorafenib was 24% (AS 27%, NAS 22%, p=0.63). This analysis was limited by inherent bias in the selection of study patients. Conclusions: AS with HCC tend to have HBV and lower MELD scores, and to undergo resection in a public health care setting with no differences in the uptake of other therapies. An analysis of survival based on ethnicity will be reported.
Relationship of novel genetically engineered mouse and the epithelial-mesenchymal transition in the metastastic progression of gastric cancers.
Authors: Kim Hark K. , Park Jun Won , Green Jeffrey E. 
Published: February 2017

3 Background: By creating mice deficient in E-cadherin, Smad4, and p53, we evaluated whether and how Cdh1 heterozygosity may accelerate the development and progression of gastric cancer, in combination with loss of Smad4 and p53. Methods: Compound conditional knockout mice of Smad4, p53, and E-cadherin were mated with Pdx-1-Cre transgenic mice. Offsprings were monitored for the development of gastric adenocarcinomas. Results: Gastric adenocarcinomas spontaneously arose in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice and recapitulated human diffuse type gastric cancers in histopathology. Gastric adenocarcinoma was more frequent in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice than in Pdx-1-Cre;Smad4F/F;Trp53F/F mice. When compared to Pdx-1-Cre;Trp53F/F;Cdh1F/F mice, Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice developed gastric adenocarcinomas more rapidly, suggesting that Smad4 and E-cadherin cooperate to constrain the development of gastric adenocarcinomas. Lung metastases were identified in three Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice, but not in the other genotypes. The epithelial-to-mesenchymal transition (EMT), characterized by increased vimentin expression, was identified at the invasive tumor front of gastric adenocarcinomas arising in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice. This phenotype was less prominent in mice with intact E-cadherin or Smad4, indicating that the suppression of EMT by E-cadherin or Smad4 may reduce metastatic signaling pathways in Pdx-1-Cre;Smad4F/F;Trp53F/F;Cdh1F/+ mice. Conclusions: Loss of E-cadherin and Smad4 cooperate with p53 loss to promote the development and metastatic progression of gastric adenocarcinomas, with similarities to human diffuse type gastric cancer. Thus, our novel genetically-engineered mouse models reveal the importance of EMT in the metastatic progression of gastric cancers, providing a unique model to test agents targeting the metastatic progression in gastric cancers.
Incidence and risk factors of thromboembolism (TE) in advanced gastric cancer (AGC) receiving chemotherapy: A prospective observational study (NCT01047618).
Authors: Ryoo Baek-Yeol , Ryu Min-Hee , Park Sook Ryun , Kang Myoung Joo , Park Kwon-Oh , Kim Jeong Hye , Kang Yoon-Koo 
Published: February 2017

31 Background: The incidence of TE in gastric cancer patients (pts) is known to be high. But because the previous reports were retrospectively analyzed in heterogeneous population, they give us only limited information. We therefore conducted a prospective study to investigate the incidence of TE and prognostic factors related with TE in AGC pts receiving chemotherapy. Methods: We checked D-dimer and coagulation battery at the start of chemotherapy and every 3 months thereafter. If there developed symptoms or signs of TE, or if D-dimer elevated 5 μg/mL or more we checked imaging studies to detect TE. The chemotherapy regimen mainly included fluoropyrimidine plus platinum-based for 1st-line, taxane-based for 2nd-line, and irinotecan-based for 3rd-line chemotherapy. Results: Between Nov 2009 and Apr 2012, 241 pts were analyzed. They received median 9 (range 1 - 42) cycles of chemotherapy. During the median observational duration of 16.7 months, 32 events (13.3%, 95% CI; 8.9 - 17.7%) of TE were detected. The types of TE were as follows; deep vein thrombosis (DVT) only in 18 (56.3%), pulmonary embolism (PE) only in 4 (12.5%), DVT and PE in 5 (15.6%), cerebral infarction in 4 (12.5%), and intra-abdominal arterial thrombosis 1 (3.1%) pts. The 1-year and 2-year cumulative incidences of TE were 15.0% (95% CI, 9.6 - 20.0%) and 20.0% (95% CI, 12.1 - 26.9%), respectively. The incidence rate of TE was 14.1 (95% CI, 9.6 - 19.9) events/100 person-years. In univariate analysis, the previous gastrectomy history, baseline CA72-4 level and baseline D-dimer level were statistically significant risk factor related with TE development. But in multivariate analysis, baseline D-dimer level was the only independent risk factor associated with TE development (Hazard ratio 2.46 [95% CI, 1.08 - 5.63], P= 0.033). Among 32 pts with baseline D-dimer 5.0 μg/mL or higher, 8 pts (25.0%) developed TE, while for pts whose baseline D-dimer was lower than 5.0 μg/mL, 24 out of 209 pts (11.5%) developed TE. Conclusions: The incidence rate of TE in AGC pts receiving chemotherapy was 14.1 (95% CI, 9.6 - 19.9) events/100 person-years. D-dimer was an important prognostic factor related with TE development. Clinical trial information: NCT01047618.
Prognostic factors and long-term outcomes of resected pancreatic adenocarcinoma: A comparison between two decades.
Authors: Serrano Aybar Pablo Emilio , Kim Peter Tae Wan , Leung Kenneth , Cleary Sean P. , Moulton Carol-anne , Greig Paul David , Gallinger Steven , Wei Alice Chia-chi 
Published: February 2017

318 Background: There have been improvements in short and long-term survival rates for patients with resected pancreatic adenocarcinoma over time The main objective of this study was to evaluate differences in long-term survival in a cohort of patients with resected pancreatic adenocarcinoma. Methods: This is a retrospective cohort study of patients who underwent pancreatic resection for pancreatic adenocarcinoma over 2 decades at a high volume academic centre. Univariate and multivariate analysis using Cox proportional hazards model were performed to evaluate prognostic factors associated with long-term survival. Time trend analyses were performed to evaluate differences between decades. Results: There were 489 patients identified, 179 patients during the early (1991-2000) and 310 during the recent decade (2001-2010). Main differences between early and recent decade were: node-positive disease rate (59% vs. 69%), number of lymph nodes collected (median 7 vs. 17), perioperative mortality (6.7% vs. 1.6%) and percentage of patients receiving adjuvant therapy (33% vs. 68%), respectively. There were no differences in sex distribution, age, margin positivity rate or tumor grade. In the multivariate analysis, node, margin status, tumor grade, adjuvant therapy and decade of resection were independently associated with overall survival for the entire cohort. Patients who received adjuvant therapy had better median overall survival: 17 [95% confidence interval (CI): 14-22] vs. 26 months (95% CI: 24-31). Median overall survival for the early and recent decade were 16 months (95% CI: 14-20) and 27 months (95% CI: 24-30, p<0.001), respectively. Conclusions: Factors associated with improved long-term survival remain comparable over time: low tumor grade, node and margin negative disease. Short and long-term survival for patients with resected pancreatic adenocarcinoma has improved in the recent decade. This is due to decreased perioperative mortality and increase use of adjuvant therapy.
Collective analysis of efficacy and safety of patients with advanced hepatocellular carcinoma (HCC) enrolled into early-phase clinical trials.
Authors: Madhusudanannair Vinu , Pollock Brad H. , Ketchum Norma , Weitman Steven , Sarantopoulos John , Mahalingam Devalingam 
Published: February 2017

320 Background: Sorafenib is the only approved systemic therapy in HCC. Clinical trials in HCC often exclude patients with Child-Pugh Stage (CPS) B/C cirrhosis. Furthermore, limited information on outcomes specific to HCC population are reported from early clinical trials. We evaluated the efficacy and safety of early phase clinical trial agents used to treat HCC. Methods: 42 consecutive patients with advanced HCC enrolled in one of the 53 phase I trials at our institution between 2003- 2013 were analyzed. Median progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves along with medians and groups were compared with the log rank test. The magnitude of association and survival was estimated with the hazard ratio (HR). Results: Median age 63 (33–84), males 75 %, ECOG PS 0–1 92%, CPS A 19%, B 71.7% and C 9.4%. 41.5% subjects were treated with prior Sorafenib. Class of agents used included cytotoxics such as microtubule inhibitors (26.4%), anti-folates (5.7%), alkylators (1.9%), topoisomerase inhibitors (5.7%), and non-cytotoxic agents such as pro-apoptotic therapies (15.1%), anti-VEGF (17%) mTOR/ EGFR/ IGFR (22.6%), and HDAC inhibitors (5.7%). When evaluating for efficacy for all patients, the mPFS (95% CI) =2.3 (1.9, 3.9) months and 12 month OS ± SEM = 59% ± 15%. The mPFS was 3.7 months versus 2.1 months for CPS A subjects and CPS B/C subjects respectively (HR 1.5, CI: 0.7- 3.5, p= 0.31). The 12-month OS was 80 ± 18% among pts with CPS A vs 74 ± 8% in CPS B. Grade 3-4 toxicity included hematologic (13.2%) and hepatic (20.8%), with no significant difference in toxicity between the two CPS groups. Finally, cytotoxic agents had a mPFS of 3.1 months (95% CI: 2.1- 4.4) vs 1.9 months (95% CI: 1.1- 2.3) for non-cytotoxic therapy (HR 1.56, 95% CI: 0.8–3.07, p = 0.19). The 12 month OS was 46% vs 50% between these two groups (HR 6.2, CI: 1.3–29.3, p = 0.009). Conclusions: Patients with advanced HCC have a modest survival that is compounded further by poor liver function. Our data suggests that there are no significant differences in efficacy and safety between HCC patients with varying liver dysfunction based on CPS status.
Stereotactic body radiation therapy for pancreatic cancer: Single institutional experience.
Authors: Moningi Shalini , Raman Siva P. , Dholakia Avani Satish , Hacker-Prietz Amy , Pawlik Timothy M. , Zheng Lei , Weiss Matthew , Laheru Daniel A. , Wolfgang Christopher Lee , Herman Joseph M. 
Published: February 2017

328 Background: Stereotactic Body Radiation Therapy (SBRT) is emerging as a possible standard treatment for pancreatic cancer; however, there is limited data to support its efficacy. This study reviews our institution’s experience using SBRT in the treatment of pancreatic cancer (PCA). Methods: Charts of all PCA patients receiving SBRT from January 2010 to June 2013 were retrospectively reviewed. The primary end points were overall survival (OS) and tumor response assessed by RECIST criteria. 95% of the PTV (GTV + 2-3 mm) received a total dose of 20-33 Gy in five fractions (4-6.6 Gy/fraction), with up to 20% heterogeneity allowed. Pre- and post-SBRT chemotherapy regimens included gemcitabine, cisplatin, FOLFIRINOX, 5-FU or paclitaxel. Results: 84 patients received SBRT, with a median follow-up time of 15.3 months. Median age was 66.5 years, 57.1% were male and 65.5% had head tumors. 66 patients received definitive SBRT for locally advanced or borderline resectable PCA, 4 patients were treated with adjuvant SBRT, and 14 received SBRT for treatment of recurrent disease. Median OS from the date of diagnosis for patients receiving definitive radiation was 17.8 mos (95% CI 14.9-20.9).For recurrent patients the median OS from first day of SBRT was 11.8 mos (95%CI 8.3-15.3). In the definitive SBRT group, among patients who were alive and had follow-up scans, the 6 and 12 month local control rate (stable or partial response) based on RECIST criteria was 84.6% and 81.8%, respectively. Five patients underwent surgery following SBRT and all had negative resection margins. Acute toxicity was minimal with most experiencing grade 1 or 2 fatigue and no grade 3/4 acute toxicity. Late grade 3/4 GI toxicity was seen in 5% (4/84) and 1 patient had a grade 5 GI bleed due to direct tumor invasion into the duodenum. Conclusions: Our early results using SBRT in the definitive and recurrent settings show favorable local control, toxicity, and survival when compared to historical outcomes using chemoradiation. Acute and late toxicity was minimal however the optimal dose and fractionation as well as normal tissue dose constraints need to be determined. Integration of SBRT with more aggressive chemotherapy may result in improved outcomes in patients with PCA.
Recurrence of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: Is there a role for locoregional treatment?
Authors: Gangi Alexandra , Menon Vijay G. , Sheckley Marwan , Tuli Richard , Hendifar Andrew Eugene , Wachsman Ashley , Nissen Nicholas N. 
Published: February 2017

329 Background: The majority of patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma (PDA) will face recurrence. While other types of metastatic tumors are often treated with loco-regional therapy, this approach is rarely applied to metastatic PDA. We examined recurrence patterns of PDA and the potential application of loco-regional treatment. Methods: Evaluation of a prospective database of patients undergoing pancreaticoduodenctomy at an academic institution by a single surgeon. Patients: Pancreaticoduodenectomy for PDA was performed in 95 patients between 2002 and 2012. Margin status was R0 in 88 (93%) and R1 in the remainder. Results: Overall median survival was 27 months and 1 and 3 year survival was 68% and 41%. Known recurrence occurred in 44 of 64 patients (69%) at a median of 20.9 months, while the status of 31 patients was unknown. The most common site of initial recurrence was liver (n=19, median 9.2 months post-surgery), followed by local recurrence (n=15; median 18.7 months) and lung (n=5; median 5.2 months). Patients with R0 margin vs R1 recurred at a median 21 vs 5 months. In our series, 6 patients (5/6 treated in the last 2 years) underwent loco-regional treatment of recurrent disease, including liver resection (n=2), stereotactic radiotherapy (n=2), hepatic ablation (n=1) or radioembolization (n=1). All 6 patients treated with loco-regional therapy are alive at a median of 15.6 months after recurrence and a median of 25.3 months since initial surgery. Conclusions: The initial site of recurrent PDA after pancreaticoduodenectomy is usually liver, and the major risk factor for recurrence is the margin status at resection. Loco-regional modalities for the treatment of recurrent PDA hold promise in select patients. The tendency to utilize loco-regional therapy for recurrent PDA is increasing and warrants continued consideration.
Outcomes of adjuvant radiotherapy and lymph node dissection in elderly patients with pancreatic cancer treated with surgery and chemotherapy.
Authors: Freilich Jessica , Mellon Eric Albert , Springett Gregory M. , Meredith Ken , Hodul Pamela Joy , Malafa Mokenge Peter , Fulp William J. , Zhao Xiuhua , Hoffe Sarah E. , Shridhar Ravi 
Published: February 2017

332 Background: To determine the effects of postoperative radiation therapy (PORT) and lymph node resection (LNR) on survival in patients age ≥ 70 with pancreatic cancer treated with surgery and chemotherapy. Methods: An analysis of patients with surgically resected pancreatic cancer who received chemotherapy from the SEER database from 2004-2008 was performed to determine association of PORT and LNR on survival. Survival curves were calculated according to the Kaplan-Meier method and log-rank analysis. Multivariate analysis (MVA) was performed by the Cox proportional hazard model. Results: We identified 961 patients who met inclusion criteria. The only significant difference between PORT patients and no PORT patients was age, median 75 and 76 years, respectively (p=0.007). Overall survival (OS) in PORT versus no PORT was not statistically different in the whole cohort (p=0.064), N0 (p=0.803) or N1 (p=0.0501). On univariate analysis (UVA) there was increased OS in patients with lower T stage (p<0.001), N0 status (p<0.001), lower AJCC stage (p<0.001) and lower grade (p<0.001). No OS difference was seen based on gender, location, or PORT. There was no difference in OS based on number of lymph nodes removed in all patients (p=0.74), N0 (p=0.59), and N1 (p=0.07). MVA for all patients revealed higher T stage, N1, and high grade were prognostic for worse mortality, while there was a trend for decreased mortality with PORT (p=0.052). In N0 patients, increased T-stage and grade were prognostic for worse survival, while PORT and number of lymph nodes removed were not. In N1 patients, higher T-stage and grade were prognostic for increased mortality, while increasing number of lymph nodes removed was associated with decreased mortality. PORT trended towards improved survival in N1 patients (p=0.06). Age, gender and tumor location were not prognostic for survival. Conclusions: Adjuvant radiation therapy and number of lymph nodes removed in patients age ≥70 does not seem to correlate with increased OS in surgically resected pancreatic cancer treated with chemotherapy. Future clinical trials will need to address age as a stratification factor for pancreatic cancer in the adjuvant setting.
Hapten-enhanced personalized chemoimmunotherapy by intratumoral drug delivery in advanced pancreatic cancer.
Authors: Yu Baofa , Lu Yuanfei 
Published: February 2017

333 Background: Currently cancer therapy is not satisfied with the effectiveness of available treatment. Engaging the power of immune system of individual patient has been considered as a highly attractive way for cancer treatment. Sipuleucel-T is an autologous cellular vaccine and represents a significant milestone for cancer immunotherapy. To evaluate the clinical effective of hapten enhanced personalized chemoimmunotherapy by intratumoral delivery of a combined drugs solution called ChemoCancerVac (CCV) in the treatment of advance pancreatic cancer and further to analyze the effect of immune adjuvant. Methods: Introtumoral injection of CCV into late stages of pancreatic cancer (92 cases), which is a proprietary therapeutic regimen composed of three components for modulation of chemoimmunotherapy, i.e. an oxidant, a cytotoxic drug and a hapten. The patients (47 patients with effect analysis and 45 patients with complete survival data were randomly divided into two groups: introtumoral chemotherapy (ITCT) alone received the CCV without hapten and introtumoral chemoimmunotherapy (ITCIT) received the CCV with the hapten. Results: In the ITCT and ITCIT groups, the clinical response rates were 92.86% and 82.88%, the median survival time and 6-month survival rate were 6.45 months vs 4.98 months and 45% vs 64%, respectively. All of mentioned above were showed no statistical difference (p>0.05), whereas 1-year survival rate of the ITCT group was 5% while that of ITCiT group was 28%. The difference was significant (p<0.05). Conclusions: The hapten enhanced personerlized immunotherapy by intratumoral injection of CCV was effective in the pancreatic cancer, meanwhile, the hapten plays an important role in prolong the patient survival time which are valuable in the clinic application.
Prospective observational study on chemotherapy-induced nausea and vomiting (CINV) for hepatobiliary and pancreatic cancer patients who were to receive chemotherapy including cisplatin by the CINV study group of Japan.
Authors: Furuse Junji , Baba Hideo , Ohkawa Shinichi , Sugimori Kazuya , Yamamoto Kazuhide , Minami Hironobu , Kitagawa Yuko , Kuramochi Hidekazu , Kwon A-Hon , Unno Michiaki , Wakabayashi Go , Aiba Keisuke , Tamura Kazuo 
Published: February 2017

341 Background: There has been no nationwide survey on CINV or validation of the guideline in Japan. The aim of the study is to investigate occurrence of CINV in hepatobiliary and pancreatic (HBP) cancer patients who are to receive chemotherapy including high and moderate emetic risk for the first time. In addition, primary care medical staffs' perception on CINV for their patients is also studied. Methods: A nationwide survey on CINV was conducted by the CINV study group of Japan. 21 institutions participated in the study. A 7-day diary for CINV was provided to the patient prior to chemotherapy to record daily occurrence and severity of CINV and an amount of food intake. Acute and delayed CINV was defined as nausea and vomiting which developed within or after 24 hours after the start of chemotherapy, respectively. The medical staffs also filled out questionnaires about their patient’s CINV. Results: A total 103 HBP cancer patients of 1,952 patients registered in this study during the period from April 2011 to December 2012 were analyzed. These patients’ diary and their medical staffs' report were sent to the central office. Underlying diseases were biliary tract cancer (70 patients), hepatocellular carcinoma (23) and pancreatic cancer (10). There were 62 males with a median age of 69 (range: 37-83) and 41 females with a median age of 63 (range: 41-80). MEC was given to 4 as was HEC to 99 patients. Acute nausea was experienced in 6 (5.8%), while was noted delayed nausea in 25 (24.3%). Acute vomiting was noted in 2 (1.9%) patients, while delayed vomiting was experienced in 6 (5.8%). The predictive factors for delayed nausea were female and motion sickness. The predictive factor for delayed vomiting was morning sickness. Medical staffs overestimated the incidence of acute and delayed nausea/vomiting. Conclusions: CINV seems to be under control with management by the guideline, but delayed nausea remained to be high and needs further investigation.