bluuebunny/crossref_metadata_2025_split huggingface dataset:
The actual accuracy of endoscopic ultrasound for detailed tumor depth determination in nonserosal exposed gastric cancer: What should we do to increase the accuracy of endoscopic ultrasound?
Authors: Lee H. , Lee J. H. 
Published: February 2017

20 Background: The accuracy of endoscopic ultrasound (EUS) for preoperative staging of gastric cancer varies. The aim of this study was to investigate the accuracy of EUS T and N staging in all and non-serosal exposed cases and identify the histopathological factors influencing accuracy. Methods: A total of 309 gastric cancer patients with confirmed pathological staging underwent EUS examination for preoperative staging at Seoul St. Mary's Hospital, Korea, between January and December 2009. Of these, 262 patients were diagnosed with non-serosal exposed gastric cancer. Results: Overall accuracies of EUS for T stage, the detailed T stages of all cases, and the detailed T stage in the non-serosal exposed group were 70.2%, 43.0%, and 41.2%, respectively. In the non-serosal exposed group, tumors greater than 5 cm in diameter were significantly associated with T overstaging (odds ratio [OR], 2.583). The overall accuracies of EUS for N staging in all cases and in the non-serosal exposed group were 71.2% and 76.7%, respectively. Tumor size (2 cm ≤ size < 5 cm; OR, 4.467; and 5 cm ≤ size; OR, 8.668) and tumor depth (submucosa; OR, 3.267; muscular propria; OR, 6.675 and subserosa; OR, 4.831) were significant factors affecting incorrect nodal detection in non-serosal exposed gastric cancer cases. Conclusions: Careful attention is required during EUS examination of large-sized gastric cancers to increase accuracy, especially for T staging. No significant financial relationships to disclose.
Comparison of ampullary adenocarcinomas and duodenal adenocarcinomas with regard to clinical outcomes and responsiveness to fluoropyrimidine-based chemotherapy.
Authors: Overman M. J. , Jiang Z. , Lal A. , Fleming J. B. , Varadhachary G. R. , Abbruzzese J. L. , Wolff R. A. 
Published: February 2017

204 Background: Though adenocarcinomas of the ampulla of Vater are classified as biliary cancers, the epithelium of origin and treatment approach for these rare tumors remains controversial. Gene expression profiling of periampullary carcinomas (GI ASCO 2011) suggest that ampullary carcinomas are more akin to duodenal than pancreaticobiliary carcinomas. Methods: Review of a M. D. Anderson Cancer Center (MDACC) periampullary surgical database from 1/1990 to 3/2010 identified 670 pancreatic, 41 extrahepatic biliary, 63 duodenal, and 131 ampullary adenocarcinomas resected at MDACC. Review of the MDACC tumor registry from 5/1990 to 1/2009 identified 240 stage I-III surgically resected ampullary adenocarcinomas seen at MDACC. 46 patients met the following inclusion criteria: MDACC confirmed pathology, distant metastatic relapse, and ≥1 cycle of either gemcitabine or fluoropyrimidine (5-FU) based first-line chemotherapy with follow-up imaging evaluation. Results: 5-year OS of patients with ampullary cancer did not differ from duodenal cancer (62% vs. 66%, p=0.19) but was significantly different from biliary (24%, p<0.001), and pancreatic cancer (17%, p<0.001). When ampullary (n=131) and duodenal (n=63) cases were stratified by T stage (T1/T2, T3/T4) or N stage (N0, N1) no statistically significant differences in OS were seen. First-line chemotherapy for metastatic ampullary carcinoma was 5-FU based in 27 patients (single agent 8, platinum 18, other 1) and gemcitabine based in 19 patients (single agent 7, platinum 8, other 4). Similar rates of prior adjuvant/neoadjvuant chemotherapy use (55% vs. 64%) and time to distant metastases (18 vs. 17m) were seen in the 5-FU and gemcitabine groups, respectively. 5-FU based chemotherapy was associated with an improved median TTP (9.1m v 4.8m, p=0.05) and trended to improve RR (44% v 21%, p=0.13) and median OS (16m vs. 12.7m, p=0.14). Conclusions: OS of resected ampullary carcinomas is similar to duodenal carcinomas but not biliary or pancreatic carcinomas. Preliminary data suggest that metastatic ampullary carcinomas may benefit more from a fluoropyrimidine-based as opposed to gemcitabine-based chemotherapy. [Table: see text]
The significance of serum interleukin-10 on the outcome of unresectable hepatocellular carcinoma (HCC).
Authors: Chan S. L. , Mo F. , Wong S. C. , Hui E. P. , Loong H. H. , Mok T. , Chan A. T. , Yeo W. 
Published: February 2017

205 Background: Serum interleukin-10 (IL-10) is associated with active hepatitis in patients (pts) with hepatitis B viral (HBV) infection. In HBV-related HCC, elevation of serum IL-10 is frequently observed but its significance on the outcome of HCC is unclear. Methods: A prospective cohort of newly diagnosed and inoperable HCC was recruited from a multidisciplinary clinic from Prince of Wales Hospital from 2006 to 2008. The baseline demographics, tumor characteristics/stage, laboratory parameters, virologic factors (HBV DNA, antiviral therapy) and first-line treatment modality were documented at the time of diagnosis. Serum IL-10 was measured by enzyme-linked immunosorbent essay. Univariate and multivariate analyses were conducted. Overall survival (OS) was the primary endpoint. Results: Total 180 new cases of inoperable HCC were evaluated. The median follow-up time was 15.5 months. Median age was 60.5 years. Most (159 pts; 88.3%) were males. 81.1% of them were positive for HBsAg. Total 120 (66.7%) had radiologic evidence of cirrhosis. 20 (11.1%), 85 (47.2%) and 75 (41.7%) received locoablative, trans- arterial/systemic therapy and supportive care respectively. The mean level of serum IL-10 was 18.1pg/ml (range: 2.8-11.7). 114 (63.3%) had log IL-10 higher than 1.0 pg/ml. Pts with log IL-10 >1.0 pg/ml had significantly worse OS than those with log IL-10≤ 1.0 pg/ml (14.8 vs. 4.5 months; HR 2.39; p<.0001). Multivariate analysis found log IL-10 (HR=2.57; p=0.005), CLIP score, TNM stage, treatment modality and the use of anti-viral therapy for HBV infection be the independent prognostic factors. Exploratory analyses showed that pts with Log IL-10>1.0pg/ml had higher ALT and HBV DNA, lower albumin, higher chance of ascites, worse Child-Pugh stage and worse tumor stage (Table). Conclusions: Serum IL-10 is an independent prognostic factor for inoperable HCC. Pts with high IL-10 level have poorer liver reserves and worse tumor staging. [Table: see text] No significant financial relationships to disclose.
Effect of a novel FAK inhibitor targeted to the binding site of VEGFR3 on pancreatic cancer proliferation in vitro and in vivo.
Authors: Kurenova E. V. , Liao J. , He D. , Hunt D. L. , Chekhau A. , Hochwald S. N. , Ostrov D. A. , Cance W. G. 
Published: February 2017

214 Background: Even with successful surgical resection and treatment pancreatic adenocarcinoma has a high incidence of recurrence because of metastatic spread. Vascular endothelial growth factor receptor 3 (VEGFR3) is related to lymphatic metastasis. VEGFR3 binds to the survival protein, focal adhesion kinase (FAK), to promote pancreatic cancer (PC) lymphangiogenesis. In this study we have pinpointed the site of interaction of VEGFR3 and FAK to create drug capable of disrupting their signaling with antitumor effect. Methods: 200,000 small molecules were screened in silico for their abilities to interact with the VEGFR3 /FAK binding site. Effects of the selected compounds on PC cell lines MiaPaCa2 and Panc1 were examined by MTT assay (viability), BrdU incorporation (proliferation), Boyden chamber (motility), TUNEL and flow cytometry (cell cycle, apoptosis), and Western blot (phosphorylation, apoptosis). Results: We selected compound C4 because it disrupted the FAK-VEGFR3 complexes in PC cells, as was shown by immunoprecipitation. It caused a dose-dependent dephosphorylation and inactivation of the VEGFR3. Inhibition of VEGFR3 with 10μM of C4 resulted in 80% reduction in cell viability, decrease in proliferation and a 50% reduction in motility. Treatment led to apoptosis in PC cells, confirmed by PARP cleavage. C4 increased the sensitivity of PC cells to chemotherapy in vitro. MiaPaca2 have shown 40% apoptosis after only 24 h of treatment with combination of C4 and gemcitabine at nanomolar concentrations ineffective alone. C4 reduced tumor growth in vivo in murine models of PC. C4 (60 mg/kg, daily IP) decreased tumor growth after 21 days of treatment to 60% (P=0.017). Lower dose of the C4 (10 mg/kg) still had an effect and inhibited tumor growth by 30%, but concomitant administration with low dose of gemcitabine (4 mg/kg, Q4dx6), had significant synergistic effect and led to 80% of tumor reduction. We also have shown that combination of C4 with gemcitabine had prolonged cytostatic effect on tumor growth after treatment withdrawal. Conclusions: Targeting the scaffolding function of FAK with the small-molecule inhibitors can be effectively used to develop potential oral-based PC therapeutics. [Table: see text]
Association of tumor PDGFR-α and PDGFR-β expression and survival after resection of hepatocellular carcinoma.
Authors: Patel S. H. , Kneuertz P. J. , Delgado M. , Cohen C. , Sarmiento J. , Staley C. A. , Kooby D. A. , Farris A. B. , Maithel S. K. 
Published: February 2017

220 Background: Hepatocellular carcinoma (HCC) proliferates through angiogenic pathways mediated, in part, by vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptors (PDGFR) α and β. We hypothesized that overexpression of these proteins is associated with decreased survival after resection. Methods: 57 patients with available tissue for analysis who underwent liver resection for HCC between 8/00 and 3/08 at one institution were identified from a prospectively maintained database. Tumors were assessed by immunohistochemistry for VEGFR2, PDGFR-α, and PDGFR-β expression and were graded by a single pathologist. Primary outcome was overall survival (OS). Results: Median age was 64 yrs; 65% were male. Median F/U was 25 mo, and OS was 26 mo. Median tumor size and number were 7 cm and 1, respectively. Macro- and microvascular invasion were present in 9% and 42% of patients, respectively. 25% had tumors that met Milan criteria. 9% had positive resection margins. 35% of patients had cirrhosis and the median nonadjusted MELD score was 7.5. Tumors exhibited differential expression of VEGFR2 (low: 79%, high: 21%), PDGFR-α (low: 93%, high: 7%), and PDGFR-β (low: 96%, high: 4%). After excluding all 30-day deaths (n=7), high PDGFR-α and β expression were independently associated with decreased OS (8.7 vs 29.1 mo, p=0.01; 2.8 vs 28.8 mo, p<0.001; respectively). When adjusted for tumor burden, margin status, and MELD score on independent multivariate analyses, both PDGFR-α and β expression were predictive of decreased survival (Table). Conclusions: High PDGFR-α and PDGFR-β expression are independently associated with decreased overall survival after resection of HCC. This finding may help to select patients who would benefit from targeted inhibitor therapy in the adjuvant setting. [Table: see text] No significant financial relationships to disclose.
Effect of diferuloyl methane (curcumin) on radiation-induced inhibition of proliferation and cytotoxicity of pancreatic cancer cells.
Authors: Tuli R. , Surmak A. , Herman J. M. 
Published: February 2017

222 Background: Pancreatic ductal adenocarcinoma carries a dismal prognosis. Unfortunately, the majority of patients present with locally advanced or metastatic disease unamenable to resection, and the benefit of radiation therapy (RT) in this population is not well substantiated. Diferuloyl methane (curcumin) is a naturally occurring polyphenol derived from the spice turmeric. Although it has been shown to have anticancer properties, it has not been well studied with radiation, particularly for pancreatic cancer. Herein, we attempt to determine whether curcumin can sensitize pancreatic cancer cells to radiation. Methods: The pancreatic carcinoma cell lines, MiaPaCa-2 and Panc02, were utilized for studies. Cells were treated with curcumin (10 nM to 1 mM), RT (1 to 9 Gy), or combinations thereof and compared to untreated controls. Cells were irradiated using a 137-Cs GammaCell in a single fraction. If applicable, cells were pretreated with curcumin one hour prior to RT. Cell viability was assessed through reduction of resazurin into fluorescent resorufin. Levels of apoptosis were determined by measuring caspase-3 and -7 activities using a luminescent assay. Results: Treatment with curcumin alone led to minimal inhibition of proliferation until concentrations exceeded 10 uM. The half maximal inhibitory concentration (IC50) was 40 uM and the IC20 was 10 uM. Cells experienced a dose- dependent inhibition of proliferation with increasing RT doses (IC20 of 5 Gy). Combined treatment with IC20 of curcumin and RT led to a synergistic increase in inhibition of proliferation (70%). The RT dose enhancement factor was 2.5 with 100 uM curcumin and 5 Gy. Caspase 3/7 activity was not significantly enhanced by treatment with curcumin alone (10 uM), but increased significantly when RT was added (5 Gy; p<.01). Conclusions: Curcumin is a potent radiosensitizer of pancreatic cancer cells that synergistically enhances the effects of RT. It has minimal effects on proliferation and apoptosis when used as a single agent at lower doses. Curcumin also potentiates RT-induced cytotoxicity through induction of apoptosis. These data are currently being validated in an orthotopic pancreatic cancer model. No significant financial relationships to disclose.
Sorafenib plus cisplatin and gemcitabine in the treatment of advanced hepatocellular carcinoma (HCC): A phase II study by the Gruppo Oncologico dell'Italia Meridionale (prot. GOIM 2705).
Authors: Giuliani F. , Febbraro A. , Addeo R. , Rizzi D. , Maiello E. , Del Prete S. , Pisconti S. , Colucci G. 
Published: February 2017

225 Background: Sorafenib is the standard treatment in advanced HCC. The combination of cisplatin and gemcitabine demonstrated to be active and well tolerated in tumors with a similar poor outcome such as pancreatic and biliary-tract cancers. Considering these data, the GOIM started a phase II trial aiming to evaluate the activity and safety of the combination of sorafenib, gemcitabine and cisplatin in advanced HCC. Methods: Patients affected by advanced HCC, not suitable for surgery or locoregional procedures, with measurable disease (Recist criteria), age ≥ 18 years, clip-score ≤3, ECOG performance status ≥ 60 (K.fsky), adequate bone marrow reserve and renal and hepatic function and who signed written informed consent, were enrolled and received cisplatin 40 mg/mq iv plus gemcitabine 800 mg/mq iv bi-weekly, while sorafenib was orally administrated at the dosage of 400 mg bid continuously. A maximum of 6 cycles of chemotherapy was planned; a maintenance with sorafenib was permitted for not progressing patients. The evaluation of activity was performed every three cycles. A Simon's two stage, two steps study design was applied: at the first step, at least 3 OR had to be observed among the first 28 patients to continue the enrollment. Up to now, 23 patients have been enrolled. Their main characteristics were: sex (male/female) 19/4, median age: 70 yrs, median PS 80,main sites of disease liver 22, lymph nodes 4, lung 2, others 3. Results: Up to now 18 patients are evaluable for activity while 5 are too early. One CR, 3 PR, 6 SD and 8 PRO for an ORR of 4/18 (22%) and a tumor control of 10/18 (55%). Twenty-one patients are evaluable for safety. The main observed side effects (%G1-2/G3-4) (NCI criteria) were: hand-foot skin reaction (HFSR) 9/14, mucositis 9/4, diarrhea 23/4, nausea/vomiting 23/0, leucopenia 23/0, anemia 9/0, thrombocytopenia 19/4, asthenia 14/14, cardiovascular 0/4, others 9/4. Conclusions: Our preliminary data seems to demonstrate that the combination of cisplatin, gemcitabine, and sorafenib is active and well tolerated in advanced HCC patients. The accrual is ongoing. No significant financial relationships to disclose.
Retrospective analysis of first-line chemotherapy in 132 patients with advanced small-bowel adenocarcinoma.
Authors: Tsushima T. , Boku N. , Honma Y. , Takahashi H. , Ueda S. , Nishina T. , Kawai H. , Kato S. , Suenaga M. , Tamura F. 
Published: February 2017

260 Background: No standard care has been established for advanced small-bowel adenocarcinoma (SBA). The aim of this study is to explore a most promising chemotherapy regimen for advanced SBA. Methods: All data were collected from medical records of patients with advanced or recurrent SBA who received chemotherapy between April 1999 and March 2009 at 41 hospitals in Japan. Selection criteria were as follows: 1) histologically proven SBA, excluding ampullary carcinoma, 2) no previous chemotherapy or radiotherapy, 3) ECOG PS 0-2, 4) adequate bone marrow, hepatic and renal functions, 5) no concomitant malignancy. Patients were divided into the five groups by regimens: group A, fluoropyrimidine alone; group B, fluoropyrimidine + cisplatin; group C, fluoropyrimidine + oxaliplatin; group D, fluoropyrimidine + irinotecan; group E, others. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Results: Demographics of selected 132 patients were: median age (range), 59 (23-78) years; male/female, 87/45; location of primary tumor, duodenum/jejunum/ileum/unknown, 80/32/17/3; advanced/recurrent disease, 91/41. The numbers of the patients in group A, B, C, D and E were 60, 17, 22, 11 and 22, and objective response rates (ORR) in the patients with target lesions were 20% (9/46), 38% (5/13), 42% (8/19), 25% (2/8), 21% (4/19), respectively. Median PFS and OS were 6.0 and 14.0 months for the whole population, and those in each group are shown in the Table.In comparison with fluoropyrimidine alone (A), oxaliplatin-combined regimens (C) associated with better PFS (HR=0.53 [0.31-0.93], p=0.03) and OS (HR=0.64 [0.33-1.25], p=0.19), while cisplatin-combined regimens (B) did not (HR=1.54 [0.88-2.68], p=0.13 for PFS and HR=1.67 [0.94-2.97], p=0.08 for OS) by univariate analysis. Conclusions: It is suggested that oxaliplatin-combined regimens might be the most promising regimen for advanced SBA. [Table: see text] No significant financial relationships to disclose.
Clinical outcomes in pancreatic adenocarcinoma (PAC) associated with a known BRCA mutation.
Authors: Lowery M. A. , Stadler Z. K. , Ludwig E. , Salo-Mullen E. , D'Adamo D. R. , Allen P. J. , Kurtz R. C. , Kelsen D. P. , O'Reilly E. M. 
Published: February 2017

268 Background: BRCA1 and -2 germ-line mutations are associated with increased risk of PAC; approximately 5% of all cases of PAC are estimated to be due to an inherited genetic mutation (Lynch, HT, et al. Pancreatology, 2001;1(5):466-471). Other BRCA-associated cancers have demonstrated increased sensitivity to platinum chemotherapy and PARP inhibitors (PARPi) with improved clinical outcomes compared to sporadic cases (J Clin Oncol, 2008 Dec 1;26(34):5530-6). Outcomes in BRCA-associated pancreatic cancer are unknown. Methods: Patients with a known BRCA1 or -2 mutation and a diagnosis of PAC were retrospectively identified from the MSKCC Familial Pancreas Cancer Registry and via institutional database review. Outcomes and clinical characteristics were reviewed. 7 patients (1 male) with BRCA2 mutation and PAC, 4 patients (1 male) with BRCA1 mutation and PAC, were identified. Two further cases of BRCA mutation and cholangiocarcinoma were identified. Results: See Table for patient demographics. Treatment for advanced disease included a PARP inhibitor (PARPi) in 2 cases; both pts had a radiologic partial response (PR) to therapy. Five patients received platinum-based chemotherapy for advanced disease, 4 of whom had a PR. Median survival for all patients was 27.6 months. Conclusions: The use of platinum- containing chemotherapy, radiation therapy, and PARPi to target the BRCA-associated defective DNA repair mechanism is deserving of further investigation in these patients. PARPi have demonstrated promising efficacy in patients with BRCA-mutated breast and ovarian cancer and are undergoing prospective evaluation in PAC. Genetic testing in patients presenting with a personal history or strong family history of BRCA associated cancers may help to guide choice of therapy. [Table: see text] No significant financial relationships to disclose.
FOLFIRI regimen as second-/third-line chemotherapy in patients with advanced pancreatic adenocarcinoma refractory to gemcitabine and platinum salts: A retrospective series of 70 patients.
Authors: Neuzillet C. , Hentic O. , Rousseau B. , Rebours V. , Bengrine-Lefèvre L. , Raymond E. , Ruszniewski P. , Louvet C. , Hammel P. 
Published: February 2017

272 Background: Gemcitabine-based regimen is a standard of first-line chemotherapy in patients with advanced pancreatic adenocarcinoma (PAC) and 5-FU/oxaliplatin combination is an option for second line (Oettle, 2009). Some data suggest a potential efficacy of 5-FU/irinotecan regimen (FOLFIRI) as first-line treatment (Taïeb, 2007)or in patients with gemcitabine/platinum-refractory advanced PAC (Yoo, 2009; Gebbia, 2010). Methods: All consecutive patients with unresectable advanced PAC (01-2005/05-2010) and OMS≤2 received FOLFIRI-1 (irinotecan 180 mg/m2 D1, n=60) or FOLFIRI-3 regimen (irinotecan 100 mg/m2 D1/D3 n=10) after failure of gemcitabine- and platinum-based chemotherapies as a systematic policy in two institutions. Following data were analyzed: tumor response, progression free survival (PFS), overall survival rate (OS), and grade 3-4 toxicities. Results: Seventy patients were studied. Median age was 60 years (range: 24-81); 37 (52.9%) were male; 30 (42.9%) were PS 0, 27 were PS 1 and 13 were PS 2. Cancer was locally advanced in 15.7% and metastatic in 84.3% of patients. Before FOLFIRI regimen, patients received 1 line (n=24, 34.3%), 2 lines (n=40, 57.1%) or ≥ 3 lines (n=6, 8.8%) chemotherapy. PFS with previous line was less than 3 months in most patients. Tumor control was achieved in 31 (44.3%) patients (partial response: 5, stable disease: 26). PFS was 17% at 12 months and 3% at 24 months. Median PFS was 23 weeks (range: 2-147). OS was 24% at 12 months and 9% at 24 months. Median OS was 24 weeks (range: 2-147). From the initial diagnosis, 1-year and 2-year survivals were 79% and 32%. Dose adaptation was required in 21 (30.0%) patients. Eighteen (25.7%) patients had grade 3-4 toxicities, mainly hematologic (n=13) or digestive (n=6). Febrile neutropenia occurred in 3 patients without death. Conclusions: FOLFIRI regimen after failure of gemcitabine- and platinum-based regimens for advanced PAC in our study had an acceptable toxicity and a surprising efficacy in patients OMS 0-2. These results suggest that FOLFIRI regimen should be further tested as first-line chemotherapy in patients with advanced pancreatic cancer. No significant financial relationships to disclose.