bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of bevacizumab on liver regeneration following hepatectomy in rats.
Authors: Mori H. , Shimada M. , Utsunomiya T. , Imura S. , Morine Y. , Ikemoto T. , Hanaoka J. , Iwahashi S. , Saito Y. , Yamada S. 
Published: February 2017

228 Background: In our clinical data, we had the interesting findings that the pathologic sinusoidal obstruction syndrome and serum hyaluronic acid after neoadjuvant oxaliplatin-associated chemotherapy for liver metastatic colorectal cancer with bevacitumab (Bev) was ameliorated compared to those without Bev. The purpose of this study was to investigate the influence of bevacizumab administration on regenerating liver in rat 70% and 90% hepatectomy (Hx) model as a surrogate model of human massive hepatectomy for liver metastatic colorectal cancer. Methods: Male Wister rats weighing 180-230g were divided into the following four groups: 70%Hx, 70%Hx + Bev, 90%Hx and 90%Hx+Bev group. The rats were pretreated with intraperitoneal administration of bevacizumab (5mg/kg) 7 days before hepatectomy. The remnant liver and blood samples were taken one day after hepatectomy, and the following parameters were evaluated: blood analysis (AST, ALT, LDH, T- Bil, and hyaluronic acid), liver weight to body weight (Lw/Bw) ratio, and postoperative survival rate for three days. Results: In the 70%Hx model, there was no significant difference between the 70%Hx group and 70%Hx + Bev group in blood analysis one day after hepatectomy; AST (1928 vs. 923 IU/L), ALT (1282 vs. 670 IU/L), T-Bil (0.17 vs. 0.19 mg/dl), LDH (3822 vs. 2967 U/L) and hyaluronic acid (995.7 vs. 1026.6 ng/ml) and in Lw/Bw ratio (1.78 vs. 1.84). In 90%Hx model, AST and ALT of blood analysis in 90%Hx+Bev group significantly decreased compared to those in 90%Hx group; AST (3428 vs. 4995 IU/L, P<0.05), ALT (1471 vs. 2287 IU/L, P<0.05), T-Bil (1.94 vs. 2.57 mg/dl), LDH (3229 vs. 5351 U/L) and hyaluronic acid (3865.7 vs. 7862.2 ng/ml). The Lw/Bw ratio in 90%Hx+Bev group significantly increased compared to that in 90%Hx group (0.80 vs. 0.67, P<0.05). The postoperative survival rate in 90%Hx+Bev group showed tendency to improve compared to that in 90%Hx group (75% vs. 50%, P=0.19). Conclusions: The administration of bevacizumab seven days before hepatectomy did not significantly affect the liver functions and liver regeneration rate. These findings suggest that hepatectomy might be safe and feasible after the use of bevacizumab. No significant financial relationships to disclose.
Molecular mechanisms underlying the synergistic interaction of the novel anticancer drug celandine with gemcitabine in preclinical models of pancreatic cancer.
Authors: Funel N. , Giovannetti E. , Del Chiaro M. , Pollina L. , Mosca F. , Peters G. , Campani D. , Boggi U. 
Published: February 2017

233 Background: Celandine (Ukrain) increased median survival in combination with gemcitabine compared to gemcitabine alone (10.4 vs. 5.2 months; p<0.001) in unresectable PDAC (Gansauge et al.; Langenbecks Arch Surg 2002). There is compelling evidence that gene transcripts of determinants of gemcitabine activity could be used to tailor PDAC chemotherapy (Giovannetti et al., Cancer Res 2006). Methods: In vitro studies were performed in two ATCC cell lines (PL45 and Mia PaCa-2) and two primary cell cultures obtained from PDAC patients who underwent surgical resections (PPTCC78 and PPTCC109). Cells were treated with celandine at IC50concentration levelsfor 48 h. The total RNA extraction was performed with TRIzol protocol. All the amplifications were carried out with normalization of gene expression against the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) housekeeping control gene, and the quantitation of gene expression was performed using the direct ratio, the standard curve method and the ΔΔCT calculation, in which the amount of target, normalized to the endogenous control and relative to the calibrator (untreated control cells) was calculated as 2(-ΔΔCt). Results: Celandine positively modulates the expression of hENT1 mRNA in all PDAC cell cultures treated with IC50 (p<0.001). The 2(-ΔΔCt) analysis revealed a mean increase of 2.8-fold (p=0.001) with respect to untreated control cells. In PL45 and Mia PaCa-2 cells celandine positively affects mRNA expression of dCK gene as well. Conclusions: To date a few options based on gemcitabine are available for treatment of PDAC. Most gemcitabine-based chemotherapy regimens resulted in a very limited disease control, and studies attempting to widen the therapeutic armamentarium against this disease are warranted. Based on the previous clinical data the celandine-gemcitabine combination appears a promising regimen and the results of the present study provide the experimental basis for the further clinical testing of the celandine-gemcitabine schedule in PDAC patients. No significant financial relationships to disclose.
Phase II trial of neoadjuvant full-dose gemcitabine, oxaliplatin, and radiation (RT) in patients with resectable (R) or borderline resectable (BR) pancreatic cancer.
Authors: Kim E. J. , Ben-Josef E. , Griffith K. A. , Herman J. M. , Wolfgang C. L. , Bekaii-Saab T. S. , Bloomston M. , Dawson L. A. , Moore M. J. , Zalupski M. M. 
Published: February 2017

239 Background: We previously developed a regimen of full dose gemcitabine (gem), oxaliplatin (ox) and RT to maximize systemic and loco-regional disease control in pancreas cancer (JCO 25:4587, 2007). A multi-institution phase II trial was conducted to test efficacy of this regimen as neoadjuvant therapy in R/BR disease. Methods: Eligibility criteria included path confirmation, no metastasis, R/BR lesion, PS ≤2, and adequate organ function. Treatment consisted of 2, 28 day cycles of gem (1g/m2 over 30 min D1, 8, 15) and ox (85mg/m2 D1, 15) with RT during cycle 1 (30Gy in 2Gy fractions). Pts were then re-evaluated for surgery. Resected pts received 2 additional cycles of chemotherapy. Results: 68 evaluable pts were treated at 4 centers in 2007-2010. Median age was 64 (42-83), 32 men, PS 0:1:2 in 40:26:2. Median tumor size 3.2 cm (1.4–7.8), lesion in head 49, body 9, tail 10, R in 24 and BR in 44. 66 pts (97%) completed cycle 1/RT and 61 (90%) cycle 2. Therapy related adverse events ≥ grade 3 in cycles1/2 included ANC (32%), plts (24%), GI (16%), biliary/cholangitis (15%). Best response in primary was partial (10%) or stable (81%). 20 pts not operated on protocol: 8 progression (4 local, 4 distant), 8 judged not resectable, 3 toxicity, 1 early death. Of 48 laparotomies,10 not resected due to vascular involvement (6) or M1 disease (4). Resection completed in 15 of 18 R pts (13 R0, 2 R1) and 23 of 30 BR pts (19 R0, 2 R1, 2 R2). 26 pts received post-op therapy. With median fu 11.3 mos (0.7-35), 42 pts are alive, 20 pts are NED. Median survival (OS) for all pts is 21.2 mos (95%CI 13.3-not defined [ND]), resected 31.1 mos (95%CI 13.7-ND), unresected 16.0 mos (95%CI 5.8-ND). Time to treatment failure (death, progression, toxicity, no resection) and OS in R pts are 9.1 mos (95%CI 2.4-23.8) and 31.1 mos (95%CI 9.8-ND) and in BR pts 5.5 mos (95%CI 2.4-11.8) and 18.0 mos (95%CI 13.3-ND). Correlation of pathologic response and outcome is ongoing. Conclusions: Neoadjuvant therapy with full dose gem, ox and RT was possible in a large proportion of pts with localized pancreas cancer and resulted in a high percentage of R0 resections. Results are particularly encouraging given a majority of pts with BR disease. [Table: see text]
Efficacy of lanreotide 30 mg as symptomatic treatment in patients with inoperable bowel obstruction due to peritoneal carcinomatosis: A randomized double-blind, placebo-controlled study.
Authors: Mariani P. , Blumberg J. , Chauvenet L. 
Published: February 2017

242 Background: Somatostatin analogues in previous open label studies improved symptoms due to bowel obstruction in patients with peritoneal carcinomatosis. This study assessed the efficacy and safety of lanreotide microparticles 30 mg as treatment of clinical symptoms in inoperable patients. Methods: Eighty cancer patients with inoperable digestive obstruction of malignant origin (mean age 62.3 years, 82.5% female) were randomized to receive one intramuscular injection either of lanreotide microparticles 30 mg (N=43) or placebo (N=37). The primary location of cancer was mostly genital (ovary 37.5%, uterus 13.8%) or digestive (colon 16.3%, stomach 11.3%, pancreas 6.3%). Most patients were fed by central parenteral route (80%) and were severely impaired (63.8% ECOG 3 or 4). The primary endpoint was the response rate at day 7 (responders defined as patients with ≤ 1 vomiting episode per day or no vomiting recurrence after removal of the NGT, for at least 3 consecutive days) assessed in a diary card in the intention to treat (ITT) population. Per protocol (PP) population mainly excludes concomitant treatment and inclusion criteria deviations defined during a blinded data review meeting. Results: In the ITT analysis, 41.9% of lanreotide 30mg treated patients were responders versus 29.7% for placebo. This difference was not statistically significant (odds ratio (OR) = 1.75 (95% CI [0.68; 4.49], p = 0.24, logistic regression). The predefinedPP (n= 49) sub group analysis did show a statistically and clinically significantly higher response rate in the lanreotide group (OR 3.60 (95% CI [1.03, 12.62], p = 0.045). There was no significant difference between the 2 treatment groups in secondary efficacy endpoints assessment but there were significant differences in favor of lanreotide in well-being using a visual analogue scale at D3 (p = 0.04), D6 (p = 0.04) and D7 (p = 0.01). No drug-related serious adverse event (SAE) or unexpected event was reported. Conclusions: Lanreotide 30 mg may decrease clinical symptoms and improve well-being in patients with inoperable bowel obstruction due to peritoneal carcinomatosis. [Table: see text]
Phase II study of sunitinib malate following hepatic artery embolization for metastatic neuroendocrine tumors.
Authors: Strosberg J. R. , Cheema A. , Campos T. , Valone T. , Kvols L. K. 
Published: February 2017

244 Background: Neuroendocrine tumors (NETs) frequently metastasize to the liver. Hepatic arterial embolization is an important therapeutic modality in treating patients with liver-predominant metastases. NETs are highly vascular and are known to express both VEGF and VEGFR. We hypothesize that administration of sunitinib, a VEGFR inhibitor, following hepatic artery embolization will delay tumor revascularization and extend progression-free survival. Methods: Patients with metastatic neuroendocrine tumors to the liver underwent a series of selective arterial embolizations followed by sunitinib (one week after each embolization, and continued until disease progression or up to a maximum of 8 cycles). Radiographic response rates were assessed by RECIST criteria. PFS and OS were calculated using Kaplan-Meier methodology. Results: 39 patients with metastatic NETs were enrolled. Primary tumor sites included the small intestine (26), pancreas (10), rectum (2), and lung (1). The initial starting dose of sunitinib was 50 mg; however, all five patients enrolled at this dose required dose reductions, and the starting dose was subsequently lowered to 37.5 mg. The majority of patients required further dose reductions to 25 mg. Twenty-eight patients (72%) experienced a partial radiographic response (PR), eight patients (20%) had stable disease, and three patients (8%) had progressive disease as their best response. Median PFS was 18 months and the rate of 1-year PFS was 72%. The rates of overall survival (OS) at 1 year and 2 years were 94% and 78%. Serum VEGF levels increased by an average of 51 pg/ml (34%) after embolization. Conclusions: Hepatic artery embolization is a highly active treatment option for patients with metastatic neuroendocrine tumors to the liver. Embolization stimulates release of VEGF into the circulation. Sunitinib can be administered following hepatic artery embolization. The high rates of progression-free survival and overall survival associated with this sequence of therapies are encouraging. [Table: see text]
The outcome of definitive or salvage radiotherapy for locally advanced hepatocellular carcinoma: A retrospective cohort study of 822 patients from a single institution.
Authors: Seong J. 
Published: February 2017

248 Background: With technological development and awareness of efficacy, radiotherapy (RT) is more frequently adopted in management of hepatocellular carcinoma (HCC). To assess the efficacy of RT, we conducted this retrospective cohort study from a single institute. Methods: The analysis involved 822 patients who underwent definitive or salvage RT for locally advanced HCC from January 1997 to August 2009. Two-dimensional RT, 3-dimensional conformal RT (3D-CRT), and intensity-modulated RT including tomotherapy (IMRT) were carried out for 186 (22.6%), 579 (70.4%), and 57 (6.9%) patients, respectively. In a majority of patients, RT was done either concurrently with intra-arterial 5-FU (500 mg/m2) chemotherapy (CCRT group; 326 patients, 39.7%), or following transarterial chemoembolization (TACE+RT group; 244 patients, 29.7%). Total radiation dose was 30 to 64.8 Gy (median dose 45 Gy) in 1.8-2 Gy fraction. Results: The median age of total 822 patients was 55 and 84.3% was male. The 2, 3, and 4-year overall survival rates of total patients were 21.2, 13.1, and 10.1%, respectively. In 2-year survival, the patients with Child-Pugh class A did better than B or C (23% vs 10.9%, p<0.001), without portal vein thrombosis (PVT) did better than with PVT (26.8% vs 14.3%, p<0.001), and without lymph node metastasis (LNM) did better than with LNM (22.9% vs 11.7%, p<0.001). Patients with total dose higher than 45 Gy did better than those with less than 45 Gy (30.1% vs. 15.6%, p<0.001). The best outcome was shown in patients received higher than 45 Gy using 3D-CRT or IMRT, with 2-year overall survival rates of 25.9% (CCRT) and 41.3% (TACE+RT). Conclusions: This study showed a substantial effect of RT in locally advanced HCC. Further analysis will be continued to provide the best option of radiotherapy for locally advanced HCC. No significant financial relationships to disclose.
Prevalence of HER2/neu overexpression/amplification in a Hispanic population with gastric adenocarcinoma.
Authors: Rodarte Shade M. , Flores Gutierrez J. , Garcia Labastida L. , Villela L. , Barbosa Quintana A. , Paredes Garcia A. , Gamboa O. , Guzman Huerta E. 
Published: February 2017

25 Background: In Europe, Asia, and North America, studies have identified that approximately 20% of patients with gastric adenocarcinoma exhibit overexpression of HER2/neu. This group of patients has been shown to benefit from combination therapy with the anti-HER2/neu monoclonal antibody trastuzumab. These findings have not been studied in Hispanics who may possess a distinct gastric cancer genotype. The aim of this study is to determine the rate of HER2/neu positivity in a completely Hispanic population with gastric adenocarcinoma and to analyze the clinical factors associated with HER2/neu. Methods: We conducted a retrospective study in three different hospitals in Monterrey, Mexico. The study population consisted of Hispanic patients with gastric adenocarcinoma who have had a gastric resection and for whom there were adequate amounts of tissue available in paraffin blocks. Tissue was tested for HER2/neu using both Immunohistochemistry (IHC) and the fluorescent in situ hybridization (FISH) techniques. Results: From 2000 to 2010, we initially evaluated 27 gastric cancer tumor samples. Sex distribution was 15 males and 12 females with a mean age of 57±15 (SD) years. Anatomic distribution of tumor was 4% in the cardias, 40% in the body and 56% in the antrum. Lauren's histological type distribution was 52% diffuse and 48% intestinal. Fifty-three percent of the tumors were high grade and nodal positivity was present in 69%. Overexpression of Her-2/neu (IHC ++ and +++) was found in five (17.4%) of the samples, being moderate (++) in two (7.4%) and strong (+++) in three (11%) tumor samples. FISH amplification for the HER2/neu gene was found in two (7.4%) tumors and was only seen in samples with a strong (+++) IHC result. There was no association identified between HER2/neu status with age, gender, degree of differentiation, T stage, or nodal status. Conclusions: In a homogeneous Hispanic population, 17.4% of gastric cancer patients were found to overexpress HER2/neu by IHC. FISH did not identify any additional HER2/neu positive tumors. It is important to consider IHC testing for HER2/neu in Hispanic gastric cancer patients as they could benefit from a chemotherapy regimen containing trastuzumab. No significant financial relationships to disclose.
Multicenter evaluation of adjuvant therapy for gallbladder cancer.
Authors: Wang J. , Hsu C. C. , Fuller C. D. , Pawlik T. M. , Miller R. C. , Czito B. G. , Tuli R. , Ben-Josef E. , Herman J. M. 
Published: February 2017

251 Background: To assess the effect of adjuvant therapy in gallbladder adenocarcinoma (GBC). Methods: Retrospective review was conducted at five institutions to identify pts who had surgery for confirmed dx of GBC from 1985-2008 (N = 189). Pts were excluded if they had chemo alone (N = 8), path other than adenoca (N= 7), carcinoma in situ (N=1), < 30 days of follow-up (N = 2), or missing data (N=14). Of the remaining 156 pts, 58 received surgery only and 98 received adj RT ± chemo. Kaplan-Meier was used for overall survival (OS) and Cox proportional hazards to compare risk factors. Results: Median age of dx was 64.4, 68.0% were female, 37.9% had ≥ stage 2b, 37.2% had + nodes, and 32.1% had + margins. Overall, 35.9% of the patients had simple cholecystectomy (SC) only and 64.1% had radical resection (ER). mOS for pts treated with surgery alone was 49.7 months (95% CI: 24.8 to Inf). On univariate analysis, + margins (HR 2.72, p<0.001) was associated with worse OS, whereas ER compared to SC improved survival in both univariate (HR 0.46, p<0.001) and multivariate (HR 0.53, p=0.033) analyses after adjusting for node/margins, T-stage, adj RT, age, gender, and institution. mOS for the entire cohort vs. adj RT (median 50.4 Gy) ± chemo was 30.7 months (95% CI: 19.2 to 46.9) vs. 26.9 months (95% CI: 15.5 to 39.1). But, compared to surgery alone, the adj group was more likely to have had node +, margin +, or T-stage 3+ (all p<0.001). The adj RT group was also less likely than surgery alone pts to have undergone ER (p = 0.007). On multivariate analysis, decreased OS was also found for node + (HR 2.09, p=0.004), margin + (HR 1.84, p=0.043), and T3/T4 disease (HR 2.37, p=0.002). After adjusting for surgical extent, node, margin, T stage, age, gender, and institution, there was improved OS with adj therapy (HR: 0.43, p = 0.020). When stratified by surgical extent, the risk estimate for adj RT improved OS among those with SC (n=56; HR 0.20, p=0.135) and ER (n=100; HR 0.46, p=0.067), but was not statistically significant. Conclusions: ER was associated with improved OS, whereas node/margin+ and T-stage 3+ were associated with worse survival. In multivariate analysis, adj RT improved OS after surgery. Given the poor prognosis of GBC patients with advanced disease, consideration of adj therapy is appropriate. No significant financial relationships to disclose.
Effect of gemcitabine on specific antitumor responses of modified vaccinia Ankara (MVA) expressing survivin in a murine pancreatic carcinoma model.
Authors: Ishizaki H. , Chijiiwa K. , Manuel E. , Srivastava T. , Song G. , Diamond D. J. , Ellenhorn J. D. 
Published: February 2017

256 Background: Survivin is overexpressed by 70% to 80% of pancreatic cancers, and is associated with resistance to chemotherapy and a poor prognosis. Gemcitabine has been a standard treatment for patients with advanced pancreatic cancer for a decade. Recent reports have demonstrated that gemcitabine treatment attenuates the tumor-suppressive environment by eliminating CD11b+/Gr- 1+ myeloid derived suppressor cells (MDSCs). We hypothesize that a cancer vaccine targeting survivin can achieve enhanced efficacy when combined with gemcitabine. Methods: In this study, we tested this hypothesis using modified vaccinia Ankara (MVA) expressing full-length murine survivin. The poorly immunogenic mouse pancreas adenocarcinoma cell line, Pan02, which expresses murine survivin and is syngeneic to C57BL/6, was used for this study. Results: Immunization with MVA-survivin resulted in a modest therapeutic antitumor effect on established Pan02 tumors. When administered with gemcitabine, MVA-survivin immunization resulted in significant tumor regression and prolonged survival. The enhanced vaccine efficacy was associated with decreased CD11b+/Gr-1+ MDSCs. To analyze thesurvivin specific immune response to MVA-survivin immunization, we utilizeda peptide library of 15mers with 11 residues overlapping fromfull-length murine survivin. Splencytes from miceimmunized with MVA-survivin produced intracellular γ-interferon inresponse to in vitro stimulation with the overlapping peptidelibrary. Increased survivin-specific CD8+ T cells that specifically recognized the Pan02 tumor line were seen in mice treated with MVA-survivin and gemcitabine. Conclusions: Thesedata suggestthat vaccination with MVA-survivin in combination with gemcitabine represents an attractive strategy to overcometumor-induced peripheral immune tolerance, and this effect has potential for clinical benefit in pancreatic cancer. No significant financial relationships to disclose.
A phase II study of neoadjuvant gemcitabine/5-fluorouracil followed by 5-fluorouracil/oxaliplatin concurrent with radiation in patients with locally advanced pancreatic cancer.
Authors: Lin C. , Kos B. M. , Sasson A. R. , Meza J. L. , Grem J. L. 
Published: February 2017

259 Background: We designed this phase II trial to determine the efficacy and safety of a neoadjuvant regimen involving gemcitabine, infusional 5-fluorouracil (5-FU), oxaliplatin and radiation therapy (RT) in patients with locally advanced pancreatic adenocarcinoma Methods: Induction chemotherapy (CT) consisted of two 3-week cycles of weekly gemcitabine with 24-hour continuous infusion of 5 FU for 2 of 3 weeks. Chemoradiation (CRT) consisted of RT of 50.4 Gy in 28 fractions or 50 Gy in 25 fractions and weekly oxaliplatin with 24-hour continuous infusion of 5 FU throughout RT. The first 7 patients also received celecoxib 200 mg BID throughout induction CT and CRT. Upon completion of CRT, surgical candidates underwent a pancreatoduodenectomy. Response rate was assessed according to RECIST criteria 4 weeks after the end of CRT. CTC AE v3 was used to grade the acute side effects. The failure-free survival (FFS), overall survival (OS) and median survival were analyzed by the Kaplan Meier method. Results: Twenty-nine patients who had borderline resectable pancreatic adenocarcinoma at the UNMC were enrolled and received induction CT. Twenty-four patients completed CRT. Nineteen patients had surgical exploration: 4 were unresectable, 6 had intra-abdominal metastases, and 9 had resection (seven had R0 resection, 2 had R1 resection, and 6 had negative nodes). The median follow up was 27 months. There were maximum 48% acute grade 3-4 toxicities during induction CT and CRT. The median FFS and OS were 7 and 10 months and the 2-year FFS and OS were 17% and 28%. Median OS and FFS for patients with and without resection was 26 vs. 9 months, p=0.06; and 19 vs. 5 months, p=0.01. Patients with CA19-9 above 90 U/L throughout treatment had significantly shorter FFS and OS than patients with CA19-9 less than 90 throughout treatment or had a decline from baseline to less than 90 after treatment. Conclusions: Induction gemcitabine/5-FU followed by 5-FU/oxaliplatin concurrent with RT led to down staging in 31% patients with subsequent resection. Further innovative strategies are needed to improve the outcome of patients with locally advanced pancreatic cancer. No significant financial relationships to disclose.