bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why African Americans are more predisposed to pancreatic cancer: Nature versus nurture.
Authors: Thompson Wesley , Latif Naeem , Rahberg Robert 
Published: March 2020

e15018 Background: There are known risk factors for pancreatic cancer like diabetes mellitus; cigarette smoking; poverty, and alcoholism; all of which are more common in African American patients than the general population. The purpose was to determine if these established risk factors were more associated within African American pancreatic cancer patients to explain their 50 – 90% increased incidence in the U.S. population. Methods: This retrospective study reviewed 172 biopsy-proven pancreatic cancer patients diagnosed over ten years at University of Florida Jacksonville. We employed linear regression models to determine statistical significance of established risk factors with prevalence of pancreatic cancer among cohorts. Results: Our data showed no increased association of diabetes, tobacco use, alcohol use between African Americans and Caucasians. However, Africans Americans as a group were twice as likely to be found at stage III or IV upon diagnosis, conferring an increased mortality risk (OR = 2.2, (95% CI 1.1 – 4.39)). Among these African Americans at advanced stage of diagnosis, females were at triple risk by odds ratio to be underinsured compared to Caucasian males (OR = 3.1, (95% CI 1.29 – 7.49, p = 0.015)). African American females were almost twice as likely to be underinsured compared to Caucasian females (OR = 1.72, (95% CI 0.646, 4.558)). The lack of healthcare access maybe related to advanced stage at diagnosis and its increased mortality risk. Conclusions: Our data suggests that the risk factors of smoking, alcoholism, and diabetes mellitus alone do not explain African Americans’ propensity for pancreatic cancer. However, lack of health insurance does confer an advanced stage at diagnosis and increased mortality risk among African American females. Our data also suggests that other etiological factors such as genetics maybe be associated with the increased risk amongst African Americans. A further investigation is warranted into genetic etiologies since African American patients have higher incidence of K-ras mutations than Caucasians; and mutated K-ras has been associated with pancreatic cancer, which is a target for therapy.
Prognostic potential of tumoral FOXP3 expression in relation with tumor-infiltrating regulatory T cells in human gastric cancers.
Authors: Suh Jungho , EO Wankyu , Kim Si-Young 
Published: March 2020

e15036 Background: Expression of the transcription factor FOXP3 is crucial for the regulatory T cells (Tregs) that engage in the maintenance of immunological self-tolerance and immune homeostasis. Recently, expression of FOXP3 in cancer cells and its association with prognosis have been shown in clinical studies. For gastric cancer, however, prognostic significance of the tumoral FOXP3 expression and its relationship with Tregs remains unknown. We observed the tumoral FOXP3 and Tregs from the 118 gastric cancer patients who underwent surgery to explore its relationships with the prognosis. Methods: Tissue samples from 118 cases of gastric cancer were used for the present study. We investigated the tumoral expression of FOXP3 and Tregs count in human gastric cancer tissue by the use of immunohistochemical analysis using a tissue microarray to explore the relation with clinicopathological variables by retrospective manner. Results: FOXP3-positive cancer cells were observed in 62 of 118 (52.5%) patients. Positive Tregs (Tregs≥10/HPF) were observed in 66 of 118 (55.9%) patients. There was significant positive relationship between positive Tregs count and the tumoral FOXP3 expression (P=0.006).Positive tumoral FOXP3 expression was significantly related with the better disease free survival but not with the overall survival. But increased Tregs count was significantly related with the better overall survival (P<0.01, P<0.01, respectively). When we divide the patients into four groups by the FOXP3 expression and the Tregs count, FOXP3/Tregs(+/+) group showed the best overall survival followed by FOXP3/Tregs(-/+) group, FOXP3/Tregs(+/-,) and FOXP3/Tregs(-/-), respectively. And the survival difference between the FOXP3/Tregs(+/+)-FOXP3/Tregs(-/+) group and the FOXP3/Tregs(+/-)-FOXP3/Tregs(-/-)group became more prominent by the Tregs count. Conclusions: These results suggest that positive tumoral FOXP3 expression in relation with the high Treg count is a new prognostic marker in gastric cancer. The combination of tumoral FOXP3 and Tregs enhanced its statistical power more than separated as a prognostic marker.
TP53 mutation and BUBR1 overexpression characterize the DNA aneuploidy of gastric cancer.
Authors: Oki Eiji , Ando Koji , Ida Satoshi , Kimura Yasue , Saeki Hiroshi , Morita Masaru , Kusumoto Tetsuya , Maehara Yoshihiko 
Published: March 2020

e15039 Background: Gastric cancers show a high frequency of DNA aneuploidy, which is a phenotype of chromosomal instability. Gastric carcinomas with aneuploidy have been shown to have higher proliferative activity and metastatic or invasive potential than diploid tumors, which leads to a poor prognosis. It has been suggested that an abnormal spindle assembly checkpoint is involved in DNA aneuploidy, but the underlying mechanism is still unclear. In this study, we focused on the TP53 gene and BUBR1 protein in gastric cancer to elucidate their relation with the features of DNA aneuploidy. Methods: The study included 178 unselected Japanese patients with primary gastric cancer who underwent gastrectomy between 1994 and 2006 at Kyushu University Hospital, Fukuoka. DNA ploidy status, TP53 gene status, and BUBR1 expression were analyzed. Nuclear DNA content was measured using laser scanning cytometry. The TP53 gene was amplified from exon 5 to exon 9, including exon-intron junctions, by PCR using p53 primers (Nippon Gene, Tokyo, Japan) and Ex Taq DNA polymerase (TaKaRa Bio Inc., Tokyo, Japan). Results: DNA aneuploidy was identified in 108 cases, and TP53 gene mutation was seen in 28 of 143 cases. Both DNA aneuploidy and TP53-mutated tumors correlated with high age and differentiated type tumors. BUBR1 aberrant expression, investigated using immunohistochemistry, was seen in 89 cases, and it correlated with malignant features such as deep invasion, and lymph node and liver metastases. DNA aneuploidy was significantly related to high BUBR1 expression (P = 0.0055), and a more significant relation was found between DNA aneuploidy and TP53mutation (P = 0.0032). Tumors with high BUBR1 expression showed poor prognosis. Conclusions: DNA aneuploidy is associated with the carcinogenesis and prognosis of gastric cancer. Therefore, there has been considerable interest in targeting cell cycle checkpoints, particularly in emerging and alternative anticancer strategies. The development of selection markers to aid in the selection of appropriate therapies for patients will be the primary focus of future research. TP53 mutation and BUBR1 expression may provide clinically useful diagnostic, therapeutic, and prognostic information.
Complications of thermal ablation of hepatic tumors: Comparison of radiofrequency and microwave techniques.
Authors: Jing Xiang , Ding Jianmin , Liu Jibin , Wang Yandong , Wang Fengmei , Wang Yijun , Du Zhi 
Published: March 2020

e15040 Background: The efficacy and safety of radiofrequency ablation (RFA) have been reported in the literatures, which are considered as frontline choice for treatment of liver cancer. Recently, microwave ablation (MWA) has emerged and gained great attention over RFA. However, in comparison to RFA, the safety of MWA for treatment of liver cancer has not been fully reported in the literatures. Studies with large clinical data sets are still needed to understand the technique and avoid the complications. The objective of this study was to retrospectively investigate the common complications of thermal ablations of liver tumors using both RFA and MWA techniques, and compare the safety between these two procedures. Methods: This retrospective study protocol was approved by our institutional ethics committee to allow investigators to review the existing patient’s medical records. A total of 879 patients with hepatic tumors underwent thermal ablation. There were 323 cases having the RFA procedures and 556 cases having MWA procedures. The complications of thermal ablations of liver tumors were compared using both RFA and MWA techniques. Results: A total of 1,030 thermal ablation sessions was performed in 879 patients with a total of 1,652 tumors. There were 323 patients with 562 tumors received a total of 376 RFA with averaged 1.16±0.48 sessions per patient. The other 556 patients with 1,090 tumors received a total of 654 MWA with averaged1.18±0.51 sessions per patient. The mortality rates were 0.31% (1/323) and 0.36% (2/556) in RFA and MWA group. In RFA and MWA group, the major complication rates were 3.5% (13/376) and 3.1% (20/654) (Table 1), meanwhile the minor complication rates were 5.9% (22/376) and 5.7% (37/654). There was no statistical significant difference for the mortality rates, the major complications, the minor complications between the RFA and MWA groups (P>0.05). Conclusions: Thermal ablation therapy in the treatment of liver cancers is relatively safe with low mortality and low incidence of serious complications. The types and incidences of complications caused by RFA and MWA are similar and comparable for safety consideration in clinical settings.
Survival of patients receiving radiofrequency ablation or ethanol injection for early-stage hepatocellular carcinoma.
Authors: Lin Zhong-Zhe , Shau Wen-Yi , Shao Yu Yun , Yeh Yi-Chun , Kuo Raymond Nien-Chen , Hsu Chiun , Hsu Chih-Hung , Cheng Ann-Lii , Lai Mei-Shu 
Published: March 2020

e15043 Background: Randomized trials suggest that radiofrequency ablation (RFA) may be more effective than percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC). However, the survival advantage of RFA need confirmation in daily practice. Methods: We conducted a population-based cohort study using the Taiwan Cancer Registry, National Health Insurance claim database and National Death Registry data from 2004 through 2009. Patients receiving PEI or RFA as first-line treatment for newly-diagnosed stage I-II HCC were enrolled. Results: A total of 658 patients receiving RFA and 378 patients receiving PEI treatment were included for final analysis. The overall survival (OS) rates of patients in the RFA and PEI groups at 5-year were 55% and 42%, respectively (p< 0.01). Compared to patients that received PEI, those that received RFA had lower risks of overall mortality and first-line treatment failure (FTF), with adjusted hazard ratios (HRs) [95% confidence interval (C.I.)] of 0.60 (0.50-0.73) for OS and 0.54 (0.46-0.64) for FTF. The favorable outcomes for the RFA group were consistently significant for patients with tumors > 2 cm as well as for those with tumors < 2 cm. Consistent results were also observed in other subgroup analyses defined by gender, age, tumor stage, and co-morbidity status. Conclusions: RFA provides better survival benefits than PEI for patients with unresectable stage I-II HCC, irrespective of tumors > 2 cm or ≤ 2 cm, in contemporary clinical practice.
Long-term survival and clinical efficacy in patients with advanced pancreatic and small bowel metastatic neuroendocrine tumors (GEP-NET) after I.V. 90Y DOTATATE.
Authors: Rogowski Wojciech , Wachula Ewa , Zok Jolanta , Lewczuk Anna , Cwikla Jaroslaw , Wysocki Piotr 
Published: March 2020

e15045 Background: Current therapeutic options for patients with progressive metastatic gastroenteropancreatic neuroendocrine tumour/neoplasm (GEP-NET/NEN) are limited. Treatment with SST analogues is method of choice, due to good symptoms control. [DOTA0, D-Phe1,Tyr3] octreotate[DOTATATE] has a higher affinity for SST2 receptors and thus is able to achieve longer disease control. The aim of this study was to evaluate long term radiological and clinical therapeutic effect of 90Y-DOTATATE in patients with progressive somatostatin receptor–positive small bowel and pancreatic neuroendocrine tumour/neoplasm (GEP-NET/NEN).The primary end point was assessing OS and PFS in long term follow-up. Methods: 67 patients progressing after treatment with SST analogues were inlcuded in the study. The mean treatment activity was 3.8GBq. The mean interval between therapies was 7 weeks (range 6 -9 weeks). Patients were treated up to mean a cumulative activity of 11.2 GBq. Due to pure beta emission (90Y) internal dosimetry was evaluated. Results: Median overall survival (OS) and progression-free survival (PFS) are shown in the Table. In univariate analysis Ki-67 (p=0.048) was the only significant factor influencing OS in pancreatic tumors. That was not confirmed in multivariate analysis. In small bowel tumors we defined three factors influencing survival in univariate analysis. These were: female gender (p=0.023), performance status at the beginning of therapy (p=0.031) and presence of liver metastases (p=0.026). Female gender (HR=0.30, 95% CI 0.11-0.81; p=0.018) was confirmed as positive prognostic factor in multivariate analysis. Factos influencing PFS were also assessed and will be presented as well. Conclusions: 90Y DOTATATE PRRT is effective in long term outcome (OS and PFS) in patient with advances progressive pancreatic and small bowel GEP-NET. This therapy is relatively safe as initial systemic therapy and after previous treatment with chemotherapy or somatostatine analogues as well. [Table: see text]
MET amplification occurrence and prediction of unfavorable clinical outcomes in patients with recurrent/metastatic gastric cancer after chemotherapy.
Authors: Li Yu-hong , An Xin , Wang Fang , Shao Qiong , Wang Feng-Hua , Wang Zhiqiang , Chen Cui , Li Cong , Luo Huiyan , Zhang Sheng Dong , Xu Rui-hua 
Published: March 2020

e15047 Background: Several large studies have reported an extremely low incidence of MET gene amplification (GA) in patients with radically resected gastric cancer. The aim of our study was to evaluate the prevalence and prognostic role of MET GA and protein expression in recurrent/metastatic gastric cancer patients who received chemotherapy. Methods: This retrospective study included 232 recurrent/metastatic gastric cancer patients. MET GA and protein expression were evaluated by fluorescent in-situ hybridization (FISH) and immunohistochemistry (IHC), respectively.Results: MET GA and strong protein expression were observed in 8.3% and 9.6% of patients, respectively. MET IHC 3+ was significantly correlated with GA. Patients with MET GA more frequently had a poor performance status (P < 0.001) and poorly differentiate tumors (P = 0.015) than those without MET GA. Both MET GA and IHC 3+ expression were associated with substantially shorter median progression free survival (PFS) and overall survival (OS). The median OS and PFS for patients with MET GA positive vs. MET GA negative were 5.7 vs. 15.5 months (P < 0.001) and 3.6 vs. 6.9 months (P < 0.001), respectively.The median OS and PFS for patients with MET IHC 3+ vs. IHC (0 to 2+) were 6.3 vs. 15.1 months (P < 0.001) and 3.6 vs. 7.0 months (P < 0.001), respectively. Conclusions: In recurrent/metastatic gastric cancer, MET amplification and strong protein expression are not rare and significantly associated with unfavorable clinical outcomes.
Low levels of radiofrequency electromagnetic fields and cancer cell proliferation in vivo.
Authors: Pasche Boris , Zimmerman Jacquelyn W. , Jimenez Hugo , Pennison Michael J. , Brezovich Ivan , Yi Nengjun , Kuster Niels , Costa Frederico , Barbault Alexandre 
Published: March 2020

e15049 Background: The incidence of hepatocellular carcinoma (HCC) is increasing but five-year survival remains dismal. Intrabuccal administration of amplitude-modulated radiofrequency electromagnetic fields (RF EMF) is a novel, non-invasive treatment modality resulting in whole body absorption of very low levels of RF EMF. Recent studies show that this approach elicits radiological responses in patients with HCC and breast cancer (J Exp Clin Cancer Res, 2009, 28:51; Br J Cancer, 2011, 105:640). Using an in vitro exposure system replicating the levels of exposure achieved in humans, we have shown that HCC cells and breast cancer cells are growth inhibited by HCC-specific and breast cancer-specific frequencies, respectively. Additionally, RF EMF exposure causes modulation of gene expression and disruption of the mitotic spindle (Br J Cancer 2012, 106:307). Methods: HCC cells were exposed to radiofrequency electromagnetic fields modulated at specific frequencies previously identified in HCC patients. MicroRNA arrays compared exposed and control groups of HCC cells. HCC cells were injected subcutaneously in NOD SCID mice. Following palpable tumor establishment, mice were exposed to HCC-specific RF EMF at a specific absorption rate of 0.4 W/kg and euthanized following excessive tumor burden. Results: We identified increased levels of miRNAs targeting proteins belonging to the PI3K pathway, specifically IP3/DAG signaling and intracellular calcium release, a pathway frequently disrupted in HCC and breast cancer. While HCC xenografts grew in control mice, we observed significant tumor shrinkage in mice exposed to HCC-specific modulation frequencies and residual xenograft tumor cells were infiltrated with fibrous tissue and showed significantly decreased proliferation and increased apoptosis. There was no evidence of altered cell proliferation or fibrosis in other organs. Conclusions: These findings are the first in vivo evidence of the efficacy of RF EMF in HCC and uncover a novel mechanism that targets cancer cell growth at specific modulation frequencies, by means of changes in PI3K signaling and release of intracellular calcium.
Activity of nab-paclitaxel (nab-P) monotherapy in heavily pretreated pancreatic cancer (aPDAC) patients (pts): A multicenter retrospective analysis.
Authors: Vaccaro Vanja , Bria Emilio , Reni Michele , Sperduti Isabella , Gelibter Alain , Nuzzo Carmen , Torsello Angela , Garufi Carlo , Lucchini Eleonora , Frizziero Melissa , Melisi Davide , Belli Carmen , Cereda Stefano , Tortora Giampaolo , Cognetti Francesco , Milella Michele 
Published: March 2020

e15057 Background: No standard treatment exists in pretreated aPDAC pts, who have already received available active drugs. nab-P has shown to improve survival in combination with GEM in first line and to be active in GEM-resistant aPDAC pts. Methods: aPDAC pts who received off-label single agent nab-P (125 or 100 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28- day cycle) as 2nd or further line of treatment for metastatic disease in three Italian centers were retrospectively reviewed. Results: 29 pts were identified (M/F: 16/13; median age: 66 yrs, range: 39-83); >50% of pts had an ECOG PS 2; median number of previous treatment lines: 2 (range 1-5); 7 pts had received Folfirinox as first line. nab-P starting dose was 125 mg/m2 in 5 pts and 100 mg/m2 in the others. A median of 2 cycles (range 1-10) were administered. Two partial responses (44 and 46-wk duration) were observed; 4 pts had stable disease SD (9, 16, 23, 28-wk duration, respectively); 5 pt are presently not evaluable. Median and mean progression free survival (PFS) were 8 (95% CI: 5-11) and 13 (95% CI: 7-18) wks, respectively; median and mean overall survival (OS) were 13 (95% CI: 9-17) and 25 (95% CI: 15-35) wks, respectively. Three- and 6-month PFS rates were 33% and 15%, respectively; 6- and 12-month OS rates were 36% and 22%, respectively. Toxicity was mild with G4 neutropenia in 1 pt and G3 neuropathy in 1 pts. With at least 10 out of 29 pts free from progression at 3 months (3-month PFS rate: 35%), our results satisfy the following post-hoc statistical hypothesis: p0: 15%, p1: 35%, a: 5%, 1-b: 80%, according to A’Hern exact single stage phase II design. Conclusions: nab-P is well tolerated and moderately active, even in heavily pretreated aPDAC pts. Further analyses are warranted, especially to identify the small proportion of pts who derive exceptionally prolonged benefit from nab-P monotherapy.
Correlation of loss of spinophilin expression with increased proliferation and viability as a prognostic factor in patients with hepatocellular carcinoma.
Authors: Ress Anna Lena , Aigelsreiter Ariane , Schauer Silvia , Eisner Florian , Samonigg Hellmut , Lackner Carolin , Haybaeck Johannes , Bauernhofer Thomas , Pichler Martin 
Published: March 2020

e15064 Background: A loss of the putative tumorsuppressor protein spinophilin has been recently involved in the pathogenesis of lung and other carcinoma types. However, a detailed study of the clinical significance and functional cellular effects of spinophilin in hepatocellular carcinoma (HCC) has never been performed. Methods: In this study, we determined for the first time the expression pattern of spinophilin and some of it´s known interacting/down-stream genes (p53, p14ARF, pRB) and proliferation markers (MIB-1 and Cyclin D) in human hepatocellular carcinoma (HCC). The prognostic relevance of spinophilin expression was determined on a cohort of 104 HCC patients who underwent primary tumor resection, followed by functional gene silencing studies. Results: Reduced spinophilin expression was detected by three independent methods (Western blot, RT-PCR and IHC) in a substantial number of patients (70%, p<0.05). Loss of spinophilin expression in HCC tissue was correlated with increased MIB-1 proliferation marker (p=0.01). In terms of clinical outcome, the disease-free survival (DFS) rate was 14.8% and 39.1% (p=0.010) and the cancer-specific survival (CSS) rate was 23.5% and 43.5% (p=0.006) for patients with low and high spinophilin expression, respectively. Multivariate Cox regression analysis identified low expression of spinophilin as an independent poor prognostic factor with respect to DFS (HR=1.8, CI=1.04-3.40, p=0.043) and CSS (HR=2.0, CI=1.1-3.8, p=0.025). Silencing of spinophilin expression in HepG2 cells was associated with increased cellular growth rate (p<0.05). Conclusions: According to our data, the loss of this putative tumor suppressor protein is an independent negative prognosticator for the clinical outcome of HCC patients. Reduced levels of spinophilin expression are associated with higher proliferation rates of HCC cells.