bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of bevacizumab on sinusoidal injury in patients receiving oxaliplatin-based chemotherapy and liver damage after massive hepatectomy in rats.
Authors: Shimada Mitsuo , Utsunomiya Toru , Hanaoka Jun , Mori Hiroki , Ikemoto Tetsuya , Imura Satoru , Morine Yuji , Miyatani Tomohiko , Sato Hirohiko , Kurita Nobuhiro 
Published: February 2017

276 Background: The aim of this study was to clarify impact of bevacizumab (Bev) on both hepatic sinusoidal injury after oxaliplatin (L-OHP)-based chemotherapy for metastatic colorectal cancer, and on liver regeneration after massive hepatectomy (Hx). Methods: <Study 1: Clinical> Fourteen patients who underwent Hx after receiving L-OHP-based chemotherapy for liver metastases from colorectal cancer were divided into two groups (Bev group (n=8) and No-Bev group (n=7)). Histology of non-cancerous liver tissue, blood chemistry such as hyaluronic acid (HA), spleen size, and postoperative complications were compared between the two groups. <Study 2: Experimental> Male Wister rats that underwent 90%-Hx were divided into two groups (Control group (n=7) and Bev group (n=7), in which Bev was injected intraperitoneally (5mg/kg) 7days before Hx). The following parameters were compared; blood chemistry, liver weight to body weight (Lw/Bw) ratio, and cytokines in liver tissues by RT-PCR, and survival rate. Results: <Study 1> Incidence of sinusoidal dilatation in Bev group was lower than that in No-Bev group (25% vs. 67%). Serum HA before Hx in Bev group (28 ng/ml).was lower than that in No-Bev group (155ng/ml). Spleen size in Bev group (174 ml) tended to be smaller than that in No-Bev group (252 ml). No significant postoperative complication was observed in Bev group, while 4 out of 7 patients had complications in No-Bev group. <Study 2> Liver damage such as ALT in Bev group (1471 IU/L) was smaller than that in Control group (2287 IU/L). Regeneration rate (Lw/Bw ratio) in Bev group was greater than that in Control group (0.80 vs. 0.67). Expression levels of IL-1β, MMP2 and MMP9 in Bev group tended to be lower than those in Control group. Survival rate at 72 hours after Hx in Bev group (83%) tended to be better than that in Control group (50%). Conclusions: Bev could reduce sinusoidal injury in patients with L-OHP-based chemotherapy, furthermore, Bev reduced liver injury and promoted liver regeneration after massive hepatectomy in rats. Those data strongly suggest Bev has beneficial effects for patients receiving L-OHP-based chemotherapy who undergo massive Hx.
Effect of non-anticancer drugs on prognosis of pancreatic cancer (PaC) receiving chemotherapy.
Authors: Nakai Yousuke , Isayama Hiroyuki , Mizuno Suguru , Sasaki Takashi , Kawakubo Kazumichi , Kogure Hirofumi , Yamamoto Natsuyo , Sasahira Naoki , Hirano Kenji , Ijichi Hideaki , Tateishi Keisuke , Tada Minoru , Koike Kazuhiko 
Published: February 2017

309 Background: Non-anticancer drugs such as metformin or statin are reported to have a potential role in cancer treatment and we previously reported inhibition of renin-angiotensin system (RAS) by angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) lead to better prognosis in PaC receiving gemcitabine (Br J Cancer 103: 1644-8). The relation between diabetes (DM) with its medication and the incidence of PaC has been described but its impact on prognosis is still unclear. Methods: We retrospectively reviewed 250 pts with advanced PaC receiving chemotherapy with gemcitabine and/or S-1 between June 2001 and April 2011 with a median follow up of 9.9 months (Mo). Univariate and multivariate analyses of progression-free survival (PFS) and overall survival (OS) were performed in pts with and without DM, using age, gender, BMI, PS, stage, protocol, DM with its treatment, hypertension (HT) with its treatment, and use of statin as variables. Results: DM was diagnosed in 124 pts (49%) and was treated with insulin or insulin analogs (n = 59), sulfonylurea (n = 38), biguanide (n = 8), thiazolidinedione (n = 6), and alpha-glucosidase inhibitor (n = 5). Statin was used in 16 pts with DM and 14 pts without DM. Locally advanced disease (44% vs. 29%) and HT (44% vs. 28%) were more prevalent in pts with DM. PFS (6.3 vs. 4.9 Mo, P = 0.440) and OS (13.3 vs. 10.0 Mo, P = 0.084) was longer in pts with DM, though not significantly. Use of statin in pts with DM was associated with longer PFS (11.6 vs. 6.0 Mo, P = 0.034) and longer OS (25.4 vs. 11.3 Mo, P = 0.006), while PFS and OS did not differ by the use of statin in pts without DM. Multivariate subgroup analysis with and without DM showed metastatic disease (Hazard ratio [HR] 2.11, P = 0.001 and HR 1.57, P = 0.013), PS 0-1 (HR 0.08, P <0.001 and HR 0.21, P <0.001), use of ACEI/ARB (HR 0.60, P = 0.030 and HR 0.46, P = 0.031) as common prognostic factors for OS. Doublet chemotherapy (HR 0.48, P = 0.007) and use of statin (HR 0.40, P = 0.010) were prognostic only in pts with DM, but any medications for DM were not significant prognostic factors. Conclusions: In our retrospective analysis, use of statin in pts with DM as well as inhibition of RAS was associated with better prognosis in pts with PaC receiving chemotherapy.
Neoadjuvant chemoradiation and intraoperative electron irradiation for locally unresectable/borderline resectable pancreas adenocarcinoma.
Authors: Ashman Jonathan Ben , Moss Adyr A , Callister Matthew D. , Reddy Kunam S , Mulligan David C , Gunderson Leonard L. , Borad Mitesh J. 
Published: February 2017

327 Background: The use of preoperative therapy for pancreatic cancer remains controversial. This study reviews our experience using neoadjuvant chemotherapy and chemoradiation (CRT) followed by surgery with intraoperative electron irradiation (IOERT) for patients with borderline resectable (BR) or unresectable (UR) tumors. Methods: A retrospective review identified 48 patients (pts) with primary BR/UR pancreas adenocarcinoma treated with preop CRT with intent to proceed to curative surgery with IOERT. Seventeen patients did not undergo attempted resection and are excluded (disease progression, 12; medically inoperable, 3; declined surgery, 2). Thirty-one patients proceeded to resection attempt and are the subject of this analysis. Kaplan-Meier survival analysis was performed using log rank test for significance. Median follow up was 19 months (mo). Results: Complete resection (R0) was achieved in 11 pts, R1 in 5, and R2 or not resected (IOERT alone) in 15 patients. Twenty-six pts died (23 of disease, 2 unrelated causes, 1 uncertain). Median overall survival (OS) was 19 mo for all pts. Local progression was detected in only 5 patients (16%) while distant disease developed in 24 (77%). Resection status significantly correlated with OS; R0/R1 patients had a median survival of 23 mo vs. 10 mo for R2/unresected tumors (p = 0.002). Three-year OS was 35% vs. 0%, respectively. Survival was not influenced by tumor location, CA19-9 baseline or response, tumor size, or initial judgment of resectability (BR vs. UR). BR tumors were resectable after neoadjuvant therapy in 9 of 11 patients (R0, 8; R1, 1) while 8 of 20 initially UR tumors underwent resection (R0, 3; R1, 4; R2, 1). Conclusions: Neoadjuvant therapy combined with IOERT has the possibility to improve patient selection for surgical resection and to optimize local therapy. Although the prognosis for locally advanced pancreatic cancer remains poor, survival was superior among patients for whom R0 or R1 resection was achieved. Distant metastasis remained the dominant pattern of failure, and novel systemic agents are needed. Prospective evaluation of the impact of neoadjuvant chemotherapy, CRT, and IOERT is warranted.
Comparison of hepatic artery embolization and selective internal radiation therapy for metastatic neuroendocrine tumors.
Authors: Engelman Eric Steven , Leon-Ferre Roberto , Naraev Boris , Sharma Nancy , Sun Shiliang , O'Dorisio Thomas M. , Halfdanarson Thorvardur Ragnar 
Published: February 2017

332 Background: Liver-directed therapies can be beneficial in reducing morbidity and mortality in patients with metastatic neuroendocrine tumors (mNETs). We compared the clinical outcomes of patients treated with hepatic artery embolization/chemoembolization (HA(C)E) or selective internal radiation therapy (SIRT) with SIR-Spheres at our institution over the last ten years. Methods: Medical records of 42 mNET patients with hepatic metastases treated with either bland hepatic artery embolization (HAE), chemoembolization (HACE), or SIRT at the University of Iowa from 2001 to 2011 were analyzed. Chi-square and Wilcoxon rank-sum tests were performed to compare the groups. Time to progression (TTP) and overall survival (OS) were calculated using Kaplain-Meier analysis. Results: The tumors were located in the small bowel in 21 patients (50%), pancreas in 8 (19%), lung in 2 (5%), and other locations in 11 patients (26%). Ten patients (24%) had extra-hepatic metastases. 13 patients had HAE, 17 patients had HACE and 12 patients had SIRT. 20 of these patients had a second procedure with 6 receiving SIRT, 9 HAE and 5 HACE. TTP was similar between SIRT (15.1 months) and HAE or HACE (19.6 months) (p= 0.968). There was a trend towards an increased TTP in patients receiving HACE (33.4 months), compared to HAE (12.1 months) or SIRT (15.1 months) (p = 0.512). The overall survival for all patients from the first intervention was 41.9 months. Conclusions: There appears to be no significant difference in TTP in patients treated with SIRT compared to patients treated with HAE or HACE in this cohort; however, there may be a trend towards a longer time to disease progression in patients treated with chemoembolization compared to the other two modalities. Patients tend to have a prolonged survival after all three liver-directed therapies.
Feasibility and potential benefits of second-line chemotherapy in patients with advanced biliary tract cancer.
Authors: Walter Thomas , Horgan Anne M. , McKeever Elizabeth , Min Trisha , McNamara Mairead , Hedley David W , Serra Stefano , Krzyzanowska Monika K. , Chen Eric Xueyu , Mackay Helen , Feld Ronald , Moore Malcolm J. , Knox Jennifer J. 
Published: February 2017

338 Background: Chemotherapy is effective in metastatic or unresectable biliary tract cancer (BTC). The benefits of second-line chemotherapy (CT2) are unclear. Methods: We retrospectively studied all patients (pts) receiving at least one cycle of chemotherapy for advanced BTC at our institution between 1991 and 2011. We analyzed pt and chemotherapy characteristics (type of regimen; tumor response; time to progression (TTP); and overall survival (OS)). The objectives were: 1) to characterize pts eligible for CT2; 2) to evaluate the efficacy of CT2. Results: 367, 89 (24%), and 24 (6%) pts received CT1, CT2, and CT3, respectively. Primary tumor location was the gallbladder (30%), intraphepatic (16%), perihilar (20%), distal common bile duct (20%), and ampulla of Vater (14%). 88% had a baseline performance status of 0-1 prior to CT1. The regimen and efficacy data of CT1 and CT2 are presented in the Table . On univariate analysis females (p=0.002) and pts with TTP >6 months on CT1 (p=0.016) were the only variables associated with receiving CT2. The only factor associated with disease control (objective response+ stable disease) on CT2 was the regimen type (75% with a doublet versus 46% with monotherapy, p=0.03). Conclusions: Among patients with advanced BTC treated with chemotherapy, less than 25% received CT2; but responses were seen and were surprisingly high even in this selected population. Pts with a longer TTP on CT1 were more likely to be offered CT2. Better disease control with CT2 occurs with a doublet than single agent, however clearly more effective therapies must be found. Updated data will be presented. [Table: see text]
Incidence and natural history of bone metastases in neuroendocrine tumors.
Authors: Keiser Jennifer , Nakakura Eric K. , Imhoff Laurel , Mayorga Margaret A. , Bobiak Sarah , Venook Alan Paul , Bergsland Emily K. 
Published: February 2017

340 Background: Bone metastases (BM) occur in carcinoids and other neuroendocrine tumors (NET), however, a comparative analysis of the incidence and natural history of BM across different NET subtypes has not been performed. We retrospectively characterized BM incidence, complications, and management across five subtypes: carcinoid/unknown primary (CARC), pancreatic NET (PNET), pheochromocytomas/paragangliomas (PHEO), adrenal cortical carcinoma (ACC) and high grade NET (HGNET) using data collected in the context of the NCCN NET Outcomes Database. Methods: 296 NET patients (pts) presenting at UCSF from 2004 to 2007 were retrospectively identified. Eligibility criteria included presentation on or after Jan 1, 2004, continued management at UCSF within one year of consultation, age over 18, and pathological confirmation of an eligible NET subtype. BM identified radiographically and/or pathologically, and classified as symptomatic (pain, pathologic fracture, or spinal cord compression) or asymptomatic. BM treatments (tx) included radiation, surgery, bisphosphonate and/or denosumab. Results: BM identified in 36/296 (12%): 29% pts with HGNET (5/17), 10% pts with CARC (12/121), 7.4% pts with PNET (6/81), 17% pt with PHEO (11/66), 18% pt with ACC (2/11). BM occurred in 21 men/15 women; median age 54. 30/36 (83%) had stage IV disease at diagnosis (dx); 69% had BM at dx. 69% pts were eventually symptomatic: bone pain (24/25, 96%), cord compression (3/25, 12%) and/or pathologic fracture (6/25, 24%); 8/25 (32%) had more than one symptom from BM. Median survival from BM: 28 mo (21.1 mo if symptomatic; 34.3 mo if asymptomatic). Overall, 81% (29/36) pt received tx for BM: 53% XRT (19/36), 25% surgery (9/36), 39% bisphosphonate (14/36), and/or 11% denosumab (4/36). Conclusions: 12% of pts with NET in this database developed BM. Most pts with BM experienced pain. Serious complications such as cord compression and/or pathological fracture occurred in 36% (9/25) suggesting that bisphosphonate and/or denosumab tx may be of value in these patients. Accrual to the database is ongoing.
Correlation of biliary stenting with clinical outcome in patients with advanced pancreatic cancer treated with chemotherapy.
Authors: Faloppi Luca , Maccaroni Elena , Giampieri Riccardo , Bianconi Maristella , Bittoni Alessandro , Del Prete Michela , Antognoli Stefania , Scartozzi Mario , Cascinu Stefano 
Published: February 2017

349 Background: The head of the pancreas is a common location for primary pancreatic tumour and therefore obstructive jaundice is a common complication deriving from this location. Although very important in the palliative treatment of this setting of patients, endoscopic procedures are an important source of complications, frequently influencing the prognosis. Aim of our analysis was to assess the clinical outcome of pancreatic cancer patients with biliary stent. Methods: We retrospectively analyzed a population of metastatic or locally advanced pancreatic cancer patients receiving at our Institution a first line chemotherapy between 2002 and 2010. Results: 163 patients were eligible for our analysis, 29 (18%) carried a biliary stent before first line treatment. A statistically significant difference in time to progression (TTP) was found in patients with or without biliary stent (respectively 2.77 months vs 4.27 months p=0,03). Clinical characteristics were homogeneous between the two groups (age, sex, performance status, stage, objective response rate, chemotherapy performed, toxicity profile). Overall survival analysis was worse in patients with biliary stent (5.93 months vs 8.33 months). In the group of patients with biliary stent toxicity was worse in patients receiving a combination chemoterapy (GEMOX). Conclusions: In our population placement of biliary stent seems to have a negative prognostic role in advanced pancreatic cancer patients. Our data also show that in patients with biliary stent the toxicity profile of chemotherapy may influence treatment adherence and clinical outcome. These observations seem to suggest that patients with obstructive jaundice even when successfully treated with plastic or metal stent may still represent a group of patients with a worse clinical outcome, not suitable for an intensive first-line approach such as FOLFIRINOX.
Helicobacter pylori and the risk of Barrett's esophagus: A meta-analysis.
Authors: Salami Augustine , Njei Basile M. , Ditah Ivo C. 
Published: February 2017

35 Background: Helicobacter pylori infection (HPI) is well known to play a role in the carcinogenesis of gastric cancer, and has been associated with MALTomas, pancreatic and colon cancer. Barrett’s esophagus (BE) is associated with a 30 fold increase risk of esophageal adenocarcinoma. However, the association of BE with HPI is unclear. The purpose of this study is to summarise all available evidence on the direction and magnitude of the association between HPI and BE. Methods: Two reviewers independently conducted a systematic search on the Cochrane library, MEDLINE and Pub Med databases from 1980 to Jan 2011. Identified articles comparing HPI in BE with controls were manually reviewed for additional references. H.pylori infection had to be confirmed by culture/serology or histology. Adjusted risk estimates were extracted and summarized using fixed-effects model. Inter-extractor discrepancies were resolved by referring to the original article. Publication bias was assessed using the Begg and Egger tests. Analysis was done using STATA version 11. Results: 21 studies (16 case control and 5 cohort studies) were eligible for analysis. These studies involved 12,458 patients. The overall pooled risk ratio for the association between HPI and BE was 0.75 (95% CI- 0.59-0.94). By study design a similar trend was observed only among the case control studies, 0.54 (95% CI 0.33-0.88). Another subgroup analysis excluding the study by Veith (“outlier”) did not change direction of association. There was no evidence of publication bias or heterogeneity among included studies. Conclusions: This study suggests that HPI is not associated with an increase risk of BE, and may actually confer decrease. These findings are consistent with previously published studies. Further data, preferably from prospective studies is needed to better elucidate the association between HPI and BE for more accurate determination.
Enhanced antitumor effect via combination of triptolide with 5-fluorouracil in pancreatic cancer cell lines.
Authors: Wang Wei 
Published: February 2017

352 Background: Pancreatic cancer is one of the most aggressive types of cancer, and lack of effective treatment results in a very low 6-month survival rate. This study aims to explore the enhancement of therapeutic effect on human pancreatic cancer cell lines (AsPC-1, MiaPaCa-2 and PANC-1) via combination of triptolide (TPL),derived from the herb Tripterygium wilfordii, and 5-fluorouracil (5-FU). Methods: Cell proliferation was measured by MTT, apoptotic cells were assessed by flow cytometry and western blot for cleaved caspase-8, 9, 3 and PARP. To explore the role of nuclear factor kappaB (NF-kB) activity in pancreatic cancer cell lines, AsPC-1/IkBaM and PANC-1/IkBaM cells (NF-kB activity of AsPC-1 and PANC-1 cells was silenced by IkB-a mutation) were treated with TPL plus 5-FU. NF-kB activity was determined by electrophoretic mobility shift assay. Results: TPL demonstrated toxicity on three pancreatic cancer cell lines with the IC50 of 25-40 nM. The combination of TPL (IC30 concentration) and 5-FU enhanced the cytotoxicity significantly compared to not only 5-FU alone but also Gemcitabine (the first line drug for advanced pancreatic cancer) alone. Combination index (CI) indicated the effect of TPL plus 5-FU was highly synergistic. Furthermore, pancreatic cancer cells treated with TPL plus 5-FU exhibited increased apoptosis, as evidenced by stronger Annexin V/ PI staining, higher levels of pro-apoptotic proteins including cleaved caspases and activated PARP compared to cells treated with TPL or 5-FU or Gemcitabine alone. In the mechanism study, AsPC-1/IkBaM and PANC-1/IkBaM cells showed more resistance to enhanced apoptosis induced by TPL plus 5-FU compared to wild-type cells. It indicated the enhanced effect of TPL was related with NF-kB activity. Conclusions: 1) TPL has a potent therapeutic effect on pancreatic cancer cell lines; 2) the combination of TPL with 5-FU enhances the therapeutic effect which is more powerful than Gemcitabine in vitro, low concentration of TPL showed high synergistic effect with 5-FU; 3) the inhibitory effect of TPL plus 5-FU on pancreatic cancer is mediated by the induction of apoptosis and TPL enhanced the apoptosis via inhibition of NF-kB activity.
Rapamycin in patients with advanced hepatocellular carcinoma progressing on prior antiangiogenic therapy.
Authors: Bouattour Mohamed , Wassermann Johanna , Dreyer Chantal , Vilgrain Valérie , Paradis Valerie , Raymond Eric , Faivre Sandrine J. 
Published: February 2017

356 Background: PI3K/Akt/mTOR is a critical survival pathway in hepatocellular carcinoma (HCC) often correlated with poor prognosis. Rapamycin (sirolimus) and its analogue everolimus, are specific mTOR inhibitors that showed promising antitumor activity in preclinical models and clinical cases of HCC Aims: To evaluate the safety and efficacy of rapamycin in patients (pts) with advanced HCC after failure or intolerance to prior antiangiogenic therapy Methods: In this retrospective cohort, we analyzed consecutive patients with progressive HCC after 1 to 3 lines of treatment including at least sorafenib. All pts received oral rapamycin at 20 to 30 mg once a week. Adverse events (AEs) were assessed using NCI-CTCAE v3.0, and tumor response was evaluated according to RECIST criteria. Results: Nine patients (F/M: 1/8) with compensated liver cirrhosis (Child A, n = 6; Child B7, n = 2) or no cirrhosis (n=1) and histologically proven HCC were included in this study. Overall, therapy with rapamycin was well tolerated. Most common toxicities were asthenia (grade 1-2: 5 pts) anaemia (all grade: 5 pts; grade 3: 2 pts ) and thrombocytopenia (grade 1-2: 2 pts). Liver function deterioration was observed in 2 pts with advanced cirrhosis (Child B7). Radiological evaluation was available in 6 pts. No objective tumor response was observed however stable disease ≥ 3 months was observed in 4 cases. Moreover, 2 pts showed stable disease at 6 months. Prolonged stabilization under rapamycin was observed in pts who were previously controlled at least for 6 months with sorafenib. Rapamycin was discontinued due to disease progression in 7/8 pts, toxicity in 1/8 pts. One pt shows ongoing long-lasting disease stabilization (8 + months). Conclusions: Rapamycin displayed an acceptable safety profile and may achieved disease stabilization in patients with heavily pretreated advanced HCC.