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1.
The utility of nutritional supportive care with an eicosapentaenoic acid (EPA)-enriched nutrition agent during pre-operative chemoradiotherapy for pancreatic cancer: Prospective randomized control study.
Akita, H, Takahashi, H, Asukai, K, Tomokuni, A, Wada, H, Marukawa, S, Yamasaki, T, Yanagimoto, Y, Takahashi, Y, Sugimura, K, et al
Clinical nutrition ESPEN. 2019;:148-153
Abstract
BACKGROUND & AIMS Neoadjuvant chemoradiotherapy (NACRT) for pancreatic cancer (PC) is potentially associated with various toxicities, which can lead to impaired nutritional status. Eicosapentaenoic acid (EPA) can reduce proinflammatory cytokines and positively influence cancer cachexia syndrome. The aim of this study is to clarify the utility of EPA enriched nutrition support during NACRT for PC. METHODS We randomly assigned 62 patients with PC that received NACRT to either a nutrition intervention (NI) or a normal diet (ND). Patients in the NI group received 2 bottles/day (550 kcal/day) of an EPA-enriched nutrition supplement during NACRT. The primary endpoints were the before-to-after NACRT ratios (post/pre ratios) of skeletal muscle mass and psoas major muscle area (PMA). The secondary endpoints were the post/pre ratios of other nutritional parameters and treatment-related toxicities. RESULTS Only 14 patients (45.2%) in the NI group consumed more than 50% of the EPA-enriched supplement provided. The post/pre ratio of skeletal muscle mass in the NI group (0.99 ± 0.060) was not significantly different from that of the ND group (0.96 ± 0.079, p = 0.102). However, patients that consumed ≥50% of the EPA-enriched supplement (the good intake group) had significantly higher skeletal muscle mass ratios than patients in the ND group (p = 0.042). The PMA ratio was significantly higher in the NI group (0.96 ± 0.081) than in the ND group (0.89 ± 0.072, p = 0.001). The NI and ND groups were not significantly different in other nutritional parameters or in NACRT-related toxicity. CONCLUSIONS We found that EPA-enriched intake could potentially improve the nutritional status of patients with PC that received NACRT, but it was difficult for many patients to drink, due to its disagreeable taste. University Hospital Medical Information Network (http://www.umin.ac.jp), registration number UMIN000033589, https://upload.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000038300.
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On infusion of high-dose ascorbate in treating cancer: Is it time for N-acetylcysteine pretreatment to enhance susceptibility and to lower side effects?
Valachová, K, Juránek, I, Rapta, P, Valent, I, Šoltés, L
Medical hypotheses. 2019;:8-9
Abstract
Ascorbate administered intravenously gives a high plasma concentration of this drug. Clinical trials with pancreatic carcinoma patients revealed their prolonged survival if treated with intravenous ascorbate. On the other hand, high plasma ascorbate concentration leads to severe side effects, such as nephrotoxicity. In the present paper, we advocate to lower intravenous ascorbate dosage along with monothiol N-acetylcysteine pretreatment due to anticipation of the same therapeutic effect but less or none of side effects. We describe in detail molecular mechanism of ascorbate action to be potentiated by N-acetylcysteine, as observed under in vitro conditions. Providing further arguments, we believe that the same mechanism may be employed in vivo.
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3.
Biosensors for early diagnosis of pancreatic cancer: a review.
Qian, L, Li, Q, Baryeh, K, Qiu, W, Li, K, Zhang, J, Yu, Q, Xu, D, Liu, W, Brand, RE, et al
Translational research : the journal of laboratory and clinical medicine. 2019;:67-89
Abstract
Pancreatic cancer is characterized by extremely high mortality and poor prognosis and is projected to be the leading cause of cancer deaths by 2030. Due to the lack of early symptoms and appropriate methods to detect pancreatic carcinoma at an early stage as well as its aggressive progression, the disease is often quite advanced by the time a definite diagnosis is established. The 5-year relative survival rate for all stages is approximately 8%. Therefore, detection of pancreatic cancer at an early surgically resectable stage is the key to decrease mortality and to improve survival. The traditional methods for diagnosing pancreatic cancer involve an imaging test, such as ultrasound or magnetic resonance imaging, paired with a biopsy of the mass in question. These methods are often expensive, time consuming, and require trained professionals to use the instruments and analyze the imaging. To overcome these issues, biosensors have been proposed as a promising tool for the early diagnosis of pancreatic cancer. The present review critically discusses the latest developments in biosensors for the early diagnosis of pancreatic cancer. Protein and microRNA biomarkers of pancreatic cancer and corresponding biosensors for pancreatic cancer diagnosis have been reviewed, and all these cases demonstrate that the emerging biosensors are becoming an increasingly relevant alternative to traditional techniques. In addition, we discuss the existing problems in biosensors and future challenges.
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4.
Systematic Review and Meta-analysis of Minimally Invasive Pancreatectomies for Solid Pseudopapillary Neoplasms of the Pancreas.
Tan, HL, Syn, N, Goh, BKP
Pancreas. 2019;(10):1334-1342
Abstract
OBJECTIVES We report the first systematic review and meta-analysis on minimally invasive pancreatectomy (MIP) for solid pseudopapillary neoplasms (SPPN) of the pancreas. METHODS A systematic review of all studies reporting patient characteristics and outcomes of MIP for SPPN was conducted. RESULTS We reviewed 27 studies comprising 149 patients with SPPN managed via MIP. Five were comparative retrospective cohort studies, comprising 46 and 60 patients in the minimally-invasive and open groups, respectively. Tumor size was smaller in the minimally-invasive group (mean difference, -2.20; 95% confidence interval (CI), -3.09 to -1.32; P < 0.001). The MI group had lower intraoperative blood loss (mean difference, -180.19; 95% CI, -344.28 to -16.09; P = 0.03) and transfusion requirement (relative risk, 0.24; 95% CI, 0.06-0.94; P = 0.04), and a shorter time to diet (mean difference, -2.99; 95% CI, -3.96 to -2.03; P < 0.001) and length of stay (mean difference, -3.61; 95% CI, -6.98 to -0.24; P = 0.04). There was no significant difference in operating time, margin positivity, postoperative morbidity, and postoperative pancreatic fistula rates. CONCLUSIONS Minimally invasive pancreatectomy for SPPN is associated with decreased intraoperative blood loss and transfusion requirements and a shorter postoperative time to diet and hospital stay.
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Meta-analysis of FOLFIRINOX regimen as the first-line chemotherapy for locally advanced pancreatic cancer and borderline resectable pancreatic cancer.
Xu, X, Wu, Q, Wang, Z, Zheng, S, Ge, K, Jia, C
Clinical and experimental medicine. 2019;(1):149-157
Abstract
The study aimed to evaluate the effectiveness of the first-line chemotherapy FOLFIRINOX in treating pancreatic cancer. Pertinent studies were derived from the PubMed, Cochrane Library and EMBASE. The outcomes were analyzed according to resection rate and radical (R0) resection rate. Data were expressed as weighted commix proportions with 95% confidence intervals (CIs). Twenty-three studies, involving 968 patients with locally advanced pancreatic cancer (LAPC) and borderline resectable pancreatic cancer (BRPC), were examined. After treatment, 55% (95% CI 52-58%) of the patients underwent resection and 40% (95% CI 37-43%) underwent R0 resection, and the median overall survival ranged from 15.5 to 35.4 months, with a 10.0-27.1 months' median progression-free survival. The meta-analysis shows that FOLFIRINOX, as the first-line therapy, has significant down-staging effects in patients with LAPC or BRPC, with a 40% R0 resection rate and the adverse events under control.
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6.
[New progress in the treatment of locally advance pancreatic cancer].
de Santibañes, M, Sanchez Clariá, R, de Santibañes, E, Pekolj, J, Mazza, O
Medicina. 2019;(Spec 6/1):576-581
Abstract
Locally advanced pancreatic cancer (LAPC) has several definitions, but it is essentially a non-metastatic tumor, in which the initial surgical resection is not considered beneficial due to the extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of chemotherapy with calcium leucovorin, fluorouracil, irinotecan hydrochloride and oxaliplatin (FOLFIRINOX) and gemcitabine-nab (nanoparticle albumin-bound)-paclitaxel (gem-nab) had very important implications for the management of patients with LAPC. After 4 to 6 months of induction chemotherapy, a large proportion of them have stable disease or even tumor regression, allowing to rescue those who initially were not candidates for surgery, with 30-35 months overall survival after surgery.
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7.
Structure-Based Virtual Screening Allows the Identification of Efficient Modulators of E-Cadherin-Mediated Cell-Cell Adhesion.
Dalle Vedove, A, Falchi, F, Donini, S, Dobric, A, Germain, S, Di Martino, GP, Prosdocimi, T, Vettraino, C, Torretta, A, Cavalli, A, et al
International journal of molecular sciences. 2019;(14)
Abstract
Cadherins are a large family of transmembrane calcium-dependent cell adhesion proteins that orchestrate adherens junction formation and are crucially involved in tissue morphogenesis. Due to their important role in cancer development and metastasis, cadherins can be considered attractive targets for drug discovery. A recent crystal structure of the complex of a cadherin extracellular portion and a small molecule inhibitor allowed the identification of a druggable interface, thus providing a viable strategy for the design of cadherin dimerization modulators. Here, we report on a structure-based virtual screening approach that led to the identification of efficient and selective modulators of E-cadherin-mediated cell-cell adhesion. Of all the putative inhibitors that were identified and experimentally tested by cell adhesion assays using human pancreatic tumor BxPC-3 cells expressing both E-cadherin and P-cadherin, two compounds turned out to be effective in inhibiting stable cell-cell adhesion at micromolar concentrations. Moreover, at the same concentrations, one of them also showed anti-invasive properties in cell invasion assays. These results will allow further development of novel and selective cadherin-mediated cell-cell adhesion modulators for the treatment of a variety of cadherin-expressing solid tumors and for improving the efficiency of drug delivery across biological barriers.
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8.
Protein Induced by Vitamin K Absence II (PIVKA-II) as a potential serological biomarker in pancreatic cancer: a pilot study.
Tartaglione, S, Pecorella, I, Zarrillo, SR, Granato, T, Viggiani, V, Manganaro, L, Marchese, C, Angeloni, A, Anastasi, E
Biochemia medica. 2019;(2):020707
Abstract
INTRODUCTION Protein induced by vitamin K absence II (PIVKA-II) is an abnormal prothrombin increased in gastrointestinal malignancy. We aimed to evaluate PIVKA-II in comparison to established pancreatic cancer (PC) biomarkers (CA 19-9, carcinoembryonic antigen (CEA) and CA 242) measured in PC patients and in patients with benign pancreatic diseases. MATERIALS AND METHODS We studied 26 PC patients (Group 1) and 20 patients with benign pancreatic diseases (Group 2). PIVKA-II and CEA were measured by chemiluminescent enzyme immunoassay method (CLEIA) on LUMIPULSE G1200 (Fujirebio-Europe, Gent, Belgium), CA 19-9 and CA 242 were measured by ELSA (CisBio Bioassays, Codolet, France) and EIA (Fujirebio Diagnostics AB, Göteborg, Sweden), respectively. Receiver operating characteristic (ROC) analysis was performed to assess biomarkers' diagnostic characteristics in both groups. RESULTS Median and interquartile range (IQR) in Group 1 and Group 2 were: 1749.0 (320.2 - 3921.0) vs. 31.0 (23.0 - 43.0) mAU/mL (P < 0.001) for PIVKA-II, 260.0 (158.7 - 272.0) vs. 45.2 (9.0 - 58.0) U/mL (P = 0.034) for CA 19-9, 104.0 (30.2 - 150.0) vs. 7.2 (4.8 - 26.0) U/mL (P < 0.050) for CA 242, 9.4 (5.3 - 37.5) vs. 4.5 (1.8 - 7.0) ng/mL (P = 0.021) for CEA. Areas under the ROC curve of PIVKA-II, CA 19-9, CA 242, CEA were 0.86 (95% CI: 0.71 - 1.00), 0.58 (95% CI: 0.38 - 0.78), 0.73 (95% CI: 0.54 - 0.92), 0.64 (95% CI: 0.44 - 0.85), respectively. CONCLUSIONS PIVKA-II is significantly higher in PC than in benign pancreatic diseases. PIVKA-II shows a rather good diagnostic performance compared to CA 19-9, CEA and CA242, thus its determination could help PC management.
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Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells.
Azzariti, A, Iacobazzi, RM, Di Fonte, R, Porcelli, L, Gristina, R, Favia, P, Fracassi, F, Trizio, I, Silvestris, N, Guida, G, et al
Scientific reports. 2019;(1):4099
Abstract
Over the past decade, cold atmospheric plasmas have shown promising application in cancer therapy. The therapeutic use of plasma-activated media is a topic addressed in an emerging field known as plasma pharmacy. In oncology, plasma-activated media are used to harness the therapeutic effects of oxidant species when they come in contact with cancer cells. Among several factors that contribute to the anticancer effect of plasma-activated liquid media (PALM), H2O2 and NO derivatives likely play a key role in the apoptotic pathway. Despite the significant amount of literature produced in recent years, a full understanding of the mechanisms by which PALM exert their activity against cancer cells is limited. In this paper, a sealed dielectric-barrier discharge was used to disentangle the effect of reactive nitrogen species (RNS) from that of reactive oxygen species (ROS) on cancer cells. Two cancers characterized by poor prognosis have been investigated: metastatic melanoma and pancreatic cancer. Both tumour models exposed to PALM rich in H2O2 showed a reduction in proliferation and an increase in calreticulin exposure and ATP release, suggesting the potential use of activated media as an inducer of immunogenic cell death via activation of the innate immune system.
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10.
Interpretation of adverse reactions and complications in Chinese expert consensus of Iodine-125 brachytherapy for pancreatic cancer.
Li, Q, Liang, Y, Zhao, Y, Gai, B
Journal of cancer research and therapeutics. 2019;(4):751-754
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Abstract
Owing to the location of the pancreas and its complex anatomical relationship, it is difficult to perform radioactive Iodine-125 seed implantation in patients with pancreatic cancer as it can cause surgical side effects and further complications. To standardize the procedure of radioactive Iodine-125 seed implantation in the treatment of pancreatic cancer and reduce the occurrence of adverse reactions and complications during and after operation, the Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee, Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, and the Radioactive Seed Therapy Branch organized and helped establish an expert consensus in China regarding radioactive Iodine-125 seed implantation in the treatment of pancreatic cancer. This article aims at interpreting the adverse reactions and complications after the implantation of radioactive seeds.