Chemopreventive Agents After Pancreatic Resection for Ductal Adenocarcinoma: Legend or Scientific Evidence?

Published on Apr 1, 2021in Annals of Surgical Oncology4.061
· DOI :10.1245/S10434-020-09097-Y
Domenico Tamburrino16
Estimated H-index: 16
(UniSR: Vita-Salute San Raffaele University),
Giovanni Guarneri4
Estimated H-index: 4
(UniSR: Vita-Salute San Raffaele University)
+ 5 AuthorsMassimo Falconi105
Estimated H-index: 105
(UniSR: Vita-Salute San Raffaele University)
Sources
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related death in the USA. A wealth of evidence has demonstrated the chemopreventive activity of aspirin, statins, and metformin against PDAC. The aim of this study is to investigate the effect of aspirin, statins, and metformin on disease-free survival (DFS) and disease-specific survival (DSS) in a large population of PDAC patients undergoing pancreatic resection. All patients who underwent pancreatic resections between January 2015 and September 2018 were retrospectively reviewed. The potentially “chemopreventive agents” considered for the analysis were aspirin, statins, and metformin. Drug use was defined in case of regular assumption at least 6 months before diagnosis and regularly after surgery along the follow-up period. A total of 430 patients were enrolled in this study, with median DFS and DSS of 21 months (IQR 13–30) months and 34 (IQR 26–52) months, respectively. On multivariable analysis, use of aspirin was associated with better DFS (HR: 0.62; p = 0.038). Metformin was associated with better DFS, without reaching statistical significance (p = 0.083). Use of statins did not influence DFS in the studied population. Aspirin, metformin, and statins were not associated with better DSS on multivariable analysis. Factors influencing DSS were pT3/pT4, N1, N2, no adjuvant treatment, G3, and ASA score > 3. The results suggest that chronic use of aspirin is associated with increased DFS but not with better DSS after surgical resection in patients with PDAC.
References29
Newest
#1Gemma Palazzolo (IIT: Istituto Italiano di Tecnologia)H-Index: 9
#2Hilaria Mollica (IIT: Istituto Italiano di Tecnologia)H-Index: 6
Last. Paolo Decuzzi (IIT: Istituto Italiano di Tecnologia)H-Index: 54
view all 10 authors...
Abstract Although screening has reduced mortality rates for colorectal cancer (CRC), about 20% of patients still carry metastases at diagnosis. Postsurgery chemotherapy is toxic and induces drug resistance. Promising alternative strategies rely on repurposing drugs such as aspirin (ASA) and metformin (MET). Here, tumor spheroids were generated in suspension by primary CRCs and metastatic lymph nodes from 11 patients. These spheroids presented a heterogeneous cell population including a small cor...
5 CitationsSource
#1Domenico Tamburrino (Sapienza University of Rome)H-Index: 16
#2Stefano CrippaH-Index: 60
Last. Gabriele CapursoH-Index: 56
view all 7 authors...
Abstract Background Previous studies on statins’ effect on survival of patients with pancreatic ductal adenocarcinoma (PDAC) report conflicting results. Aims To evaluate the association between statin use and PDAC patients’ survival. Methods A systematic review and meta-analysis was performed including case-control, cohort studies and randomized controlled trials assessing the association between statin use and survival in PDAC patients. Pooled HRs with 95%CIs were calculated using random effect...
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#1Fang Hao (Tianjin Medical University)H-Index: 3
#2Qinhong Xu (Xi'an Jiaotong University)H-Index: 2
Last. Enrique Rozengurt (UCLA: University of California, Los Angeles)H-Index: 118
view all 8 authors...
Author(s): Hao, Fang; Xu, Qinhong; Wang, Jing; Yu, Shuo; Chang, Hui-Hua; Sinnett-Smith, James; Eibl, Guido; Rozengurt, Enrique | Abstract: We examined the impact of statins on Yes-associated Protein (YAP) localization, phosphorylation and transcriptional activity in human and mouse pancreatic ductal adenocarcinoma (PDAC) cells. Exposure of sparse cultures of PANC-1 and MiaPaCa-2 cells to cerivastatin or simvastatin induced a striking re-localization of YAP from the nucleus to the cytoplasm and i...
9 CitationsSource
#1Vanessa Selak (University of Auckland)H-Index: 6
#2Rod Jackson (University of Auckland)H-Index: 54
Last. Sue Wells (University of Auckland)H-Index: 23
view all 10 authors...
Background: Many prognostic models for cardiovascular risk can be used to estimate aspirin's absolute benefits, but few bleeding risk models are available to estimate its likely harms. Objective: To develop prognostic bleeding risk models among persons in whom aspirin might be considered for the primary prevention of cardiovascular disease (CVD). Design: Prospective cohort study. Setting: New Zealand primary care. Participants: The study cohort comprised 385 191 persons aged 30 to 79 years whose...
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#1Vanessa SelakH-Index: 6
#2Rod JacksonH-Index: 54
Last. Sue WellsH-Index: 23
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Several prognostic models estimate potential cardiovascular benefits of using aspirin for primary prevention. This prognostic model estimates bleeding risk among persons in whom aspirin may be cons...
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#1Livia Archibugi (UniSR: Vita-Salute San Raffaele University)H-Index: 13
#2Paolo Giorgio Arcidiacono (UniSR: Vita-Salute San Raffaele University)H-Index: 40
Last. Gabriele Capurso (UniSR: Vita-Salute San Raffaele University)H-Index: 56
view all 3 authors...
Abstract Background Previous studies investigating the association between statin use and pancreatic cancer (PDAC) risk for a possible chemopreventive effect gathered heterogeneous results. Aims To conduct a systematic review and meta-analysis to clarify this association. Methods Comprehensive literature search of articles published up to February 2018, including case-control (CC),cohort studies (C), randomized controlled trials (RCTs) assessing association between statin use and PDAC risk. Stud...
17 CitationsSource
#1Weikun Qian (Xi'an Jiaotong University)H-Index: 13
#2Jie Li (Xi'an Jiaotong University)H-Index: 23
Last. Wanxing Duan (Xi'an Jiaotong University)H-Index: 24
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Abstract Aims Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases and has few effective and reliable therapeutic strategies. The anti-tumor effect of metformin is widely known, however, there is only limited evidence regarding the anti-angiogenesis effect and chemosensitization of metformin and its underlying mechanisms in PDAC. Main methods In the present study, we adopted a spontaneous PDAC mouse model named LSL‑KrasG12D/+; Trp53fl/+; Pdx1‑Cre (KPC) mice to explore th...
21 CitationsSource
: Despite new and exciting research and renewed optimism about future therapy, current statistics of survival from pancreatic cancer remains dismal. Patients seeking alternative or complementary treatments should be warned to avoid the hype and instead look to real science. A variety of relatively safe and inexpensive treatment options that have shown success in preclinical models and/or retrospective studies are currently available. Patients require their physicians to provide therapeutic guida...
12 CitationsSource
#1Shuji Isaji (Mie University)H-Index: 38
#2Shugo Mizuno (Mie University)H-Index: 23
Last. Christopher L. Wolfgang (Johns Hopkins University)H-Index: 102
view all 13 authors...
This statement was developed to promote international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) which was adopted by the National Comprehensive Cancer Network (NCCN) in 2006, but which has changed yearly and become more complicated. Based on a symposium held during the 20th meeting of the International Association of Pancreatology (IAP) in Sendai, Japan, in 2016, the presenters sought consensus on issues related to BR-PDAC. We defined patient...
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#1Livia Archibugi (Sapienza University of Rome)H-Index: 13
#2Matteo Piciucchi (Sapienza University of Rome)H-Index: 12
Last. Gabriele Capurso (Sapienza University of Rome)H-Index: 56
view all 10 authors...
Data on the association between aspirin and statin use and Pancreatic Ductal AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed, but no studies evaluated the potential combined or confounding effect of the two at the same time. We aimed to investigate the association between aspirin and statin exclusive and combined use and PDAC occurrence. Data on environmental factors, family and medical history were screened in a case-control study. PDAC cases were matched to cont...
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Pancreatic ductal adenocarcinoma continues to be a lethal disease, for which efficient treatment options are very limited. Increasing efforts have been taken to understand how to prevent or intercept this disease at an early stage. There is convincing evidence from epidemiologic and preclinical studies that the antidiabetic drug metformin possesses beneficial effects in pancreatic cancer, including reducing the risk of developing the disease and improving survival in patients with early-stage di...
Source
#1Domenico TamburrinoH-Index: 16
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