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Pancreatic Neoplasms: HELP
Articles by Tessa Ya Sung Le Large
Based on 13 articles published since 2010
(Why 13 articles?)
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Between 2010 and 2020, T. Y. Le Large wrote the following 13 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Key biological processes driving metastatic spread of pancreatic cancer as identified by multi-omics studies. 2017

Le Large, T Y S / Bijlsma, M F / Kazemier, G / van Laarhoven, H W M / Giovannetti, E / Jimenez, C R. ·Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands; Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · Laboratory of Experimental Oncology and Radiobiology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Cancer Pharmacology Lab, AIRC Start Up Unit, University of Pisa, Pisa, Italy; CNR-Nano, Institute of Nanoscience and Nanotechnology, Pisa, Italy. · Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: c.jimenez@vumc.nl. ·Semin Cancer Biol · Pubmed #28366542.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by a high metastatic burden, already at the time of diagnosis. The metastatic potential of PDAC is one of the main reasons for the poor outcome next to lack of significant improvement in effective treatments in the last decade. Key mutated driver genes, such as activating KRAS mutations, are concordantly expressed in primary and metastatic tumors. However, the biology behind the metastatic potential of PDAC is not fully understood. Recently, large-scale omic approaches have revealed new mechanisms by which PDAC cells gain their metastatic potency. In particular, genomic studies have shown that multiple heterogeneous subclones reside in the primary tumor with different metastatic potential. The development of metastases may be correlated to a more mesenchymal transcriptomic subtype. However, for cancer cells to survive in a distant organ, metastatic sites need to be modulated into pre-metastatic niches. Proteomic studies identified the influence of exosomes on the Kuppfer cells in the liver, which could function to prepare this tissue for metastatic colonization. Phosphoproteomics adds an extra layer to the established omic techniques by unravelling key functional signaling. Future studies integrating results from these large-scale omic approaches will hopefully improve PDAC prognosis through identification of new therapeutic targets and patient selection tools. In this article, we will review the current knowledge on the biology of PDAC metastasis unravelled by large scale multi-omic approaches.

2 Review Surveillance strategy for small asymptomatic non-functional pancreatic neuroendocrine tumors - a systematic review and meta-analysis. 2017

Sallinen, Ville / Le Large, Tessa Y S / Galeev, Shamil / Kovalenko, Zahar / Tieftrunk, Elke / Araujo, Raphael / Ceyhan, Güralp O / Gaujoux, Sebastien. ·Department of Abdominal Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Department of Transplantation and Liver Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. Electronic address: ville.sallinen@helsinki.fi. · Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · General Surgery Department, Saint Luke's Clinical Hospital, Saint-Petersburg, Russia. · Federal Medical and Rehabilitation Center, Department of Surgical Oncology, Moscow, Russia. · Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. · Department of Upper Gastrointestinal and Hepato-Pancreato-Biliary Surgery, Barretos Cancer Hospital, Barretos, São Paulo, Brazil. · Department of Digestive and Endocrine Surgery, Cochin Hospital, APHP, Paris, France; Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, France. Electronic address: sebastien.gaujoux@aphp.fr. ·HPB (Oxford) · Pubmed #28254159.

ABSTRACT: BACKGROUND: Non-functional pancreatic neuroendocrine tumors (NF-PNET) are rare neoplasms being increasingly diagnosed. Surgical treatment or expectant management are both suggested for small NF-PNETs. The aim of this study was to evaluate the outcome of surveillance strategy for small NF-PNETs. METHODS: A systematic search was performed up to March 2016 in MEDLINE, EMBASE and the Cochrane Library according to the PRISMA guidelines. Data was pooled using the random-effects model. RESULTS: Nine articles including 344 patients with sporadic and 64 patients with MEN1 related NF-PNET were selected. Tumor growth was observed in 22% and 52%, development of metastases were reported on 0% and 9%, and rate of secondary surgical resection was 12% and 25% in patients with sporadic or MEN1 related NF-PNETs, respectively. All metastases (1 distant, 4 nodal) were reported by a single study in patients with MEN1. Reason for secondary surgery was tumor growth in half of patients undergoing surgery. DISCUSSION: Expectant management of small asymptomatic, sporadic, NF-PNETs could be a reasonable option in highly selected patients. However, the level of evidence is low and longer follow-up is needed to identify patients could benefit from upfront surgery instead of expectant treatment.

3 Review FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer. 2016

Caparello, Chiara / Meijer, Laura L / Garajova, Ingrid / Falcone, Alfredo / Le Large, Tessa Y / Funel, Niccola / Kazemier, Geert / Peters, Godefridus J / Vasile, Enrico / Giovannetti, Elisa. ·Chiara Caparello, Alfredo Falcone, Niccola Funel, Enrico Vasile, Elisa Giovannetti, University Hospital of Pisa, 56124 Pisa, Italy. ·World J Gastroenterol · Pubmed #27610011.

ABSTRACT: Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase III trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARC levels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microRNAs as predictive biomarkers.

4 Review Bioinformatic analysis reveals pancreatic cancer molecular subtypes specific to the tumor and the microenvironment. 2016

Le Large, Tessa Y S / Mato Prado, Mireia / Krell, Jonathan / Bijlsma, Maarten F / Meijer, Laura L / Kazemier, Geert / Frampton, Adam E / Giovannetti, Elisa. ·a Department of Surgery , VU University Medical Center , Amsterdam , The Netherlands. · b Department of Medical Oncology , VU University Medical Center , Amsterdam , The Netherlands. · c Department of Medical Oncology , Academic Medical Center , Amsterdam , The Netherlands. · d Division of Cancer, Department of Surgery & Cancer, Imperial Centre for Translational and Experimental Medicine (ICTEM) , Imperial College , London , UK. · e HPB Surgical Unit, Department of Surgery & Cancer , Imperial College , London , UK. · f Cancer Pharmacology Lab, AIRC Start-Up Unit , University of Pisa , Pisa , Italy. · g CNR-Nano , Institute of Nanoscience and Nanotechnology , Pisa , Italy. ·Expert Rev Mol Diagn · Pubmed #27118062.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease characterized by a dense desmoplastic reaction surrounding malignant epithelial cells. Interaction between the epithelial and stromal compartments is suggested to enhance its aggressive nature. Indeed, therapies targeting the stroma, as well as the tumor cells, may improve survival outcomes for patients. The evaluated study by Moffitt et al. used bioinformatic techniques to separate gene expression patterns of normal tissues from PDAC and stroma in a large cohort of samples. The researchers identified two different subtypes of PDAC ('classical' and 'basal-like') and surrounding stroma ('normal' and 'activated'). The basal-like subtype was associated with worse prognosis and a trend towards better response to adjuvant therapy. Hopefully, the molecular stratification of PDAC will potentially allow more personalized treatment strategies and guide clinical decision making.

5 Review Molecular mechanisms underlying the role of microRNAs in the chemoresistance of pancreatic cancer. 2014

Garajová, Ingrid / Le Large, Tessa Y / Frampton, Adam E / Rolfo, Christian / Voortman, Johannes / Giovannetti, Elisa. ·Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ; Department of Experimental, Diagnostic and Speciality Medicine, University of Bologna, Sant'Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. · Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. · HPB Surgical Unit, Department of Surgery & Cancer, Imperial College, Hammersmith Hospital Campus, White City, London W12 0NN, UK. · Phase I-Early Clinical Trials Unit, Department of Medical Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium. · Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands ; Start-Up Unit, University of Pisa, Lungarno Pacinotti 43, 56126 Pisa, Italy. ·Biomed Res Int · Pubmed #25250326.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

6 Article Combined Expression of Plasma Thrombospondin-2 and CA19-9 for Diagnosis of Pancreatic Cancer and Distal Cholangiocarcinoma: A Proteome Approach. 2020

Le Large, Tessa Y S / Meijer, Laura L / Paleckyte, Rosita / Boyd, Lenka N C / Kok, Bart / Wurdinger, Thomas / Schelfhorst, Tim / Piersma, Sander R / Pham, Thang V / van Grieken, Nicole C T / Zonderhuis, Barbara M / Daams, Freek / van Laarhoven, Hanneke W M / Bijlsma, Maarten F / Jimenez, Connie R / Giovannetti, Elisa / Kazemier, Geert. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands. · Department of Pathology, Cancer Center Amsterdam, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands. · Laboratory of Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Cancer Pharmacology Lab, Associazione Italiana per la Ricerca sul Cancro (AIRC) Start-Up Unit, Fondazione Pisana per la Scienza, University of Pisa, Pisa, Italy. ·Oncologist · Pubmed #31943574.

ABSTRACT: BACKGROUND: Minimally invasive diagnostic biomarkers for patients with pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are warranted to facilitate accurate diagnosis. This study identified diagnostic plasma proteins based on proteomics of tumor secretome. MATERIALS AND METHODS: Secretome of tumor and normal tissue was collected after resection of PDAC and dCCA. Differentially expressed proteins were measured by mass spectrometry. Selected candidate biomarkers and carbohydrate antigen 19-9 (CA19-9) were validated by enzyme-linked immunosorbent assay in plasma from patients with PDAC (n = 82), dCCA (n = 29), benign disease (BD; n = 30), and healthy donors (HDs; n = 50). Areas under the curve (AUCs) of receiver operator characteristic curves were calculated to determine the discriminative power. RESULTS: In tumor secretome, 696 discriminatory proteins were identified, including 21 candidate biomarkers. Thrombospondin-2 (THBS2) emerged as promising biomarker. Abundance of THBS2 in plasma from patients with cancer was significantly higher compared to HDs (p < .001, AUC = 0.844). Combined expression of THBS2 and CA19-9 yielded the optimal discriminatory capacity (AUC = 0.952), similarly for early- and late-stage disease (AUC = 0.971 and AUC = 0.911). Remarkably, this combination demonstrated a power similar to CA19-9 to discriminate cancer from BD (AUC = 0.764), and THBS2 provided an additive value in patients with high expression levels of bilirubin. CONCLUSION: Our proteome approach identified a promising set of candidate biomarkers. The combined plasma expression of THBS2/CA19-9 is able to accurately distinguish patients with PDAC or dCCA from HD and BD. IMPLICATIONS FOR PRACTICE: The combined plasma expression of thrombospondin-2 and carbohydrate antigen 19-9 is able to accurately diagnose patients with pancreatic cancer and distal cholangiocarcinoma. This will facilitate minimally invasive diagnosis for these patients by distinguishing them from healthy individuals and benign diseases.

7 Article Unravelling the Diagnostic Dilemma: A MicroRNA Panel of Circulating MiR-16 and MiR-877 as A Diagnostic Classifier for Distal Bile Duct Tumors. 2019

Meijer, Laura L / Puik, Jisce R / Le Large, Tessa Y S / Heger, Michal / Dijk, Frederike / Funel, Niccola / Wurdinger, Thomas / Garajová, Ingrid / van Grieken, Nicole C T / van de Wiel, Mark A / Giovannetti, Elisa / Kazemier, Geert. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands. · Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC, University of Amsterdam, 1105 AZ, The Netherlands. · Department of Experimental Surgery, Amsterdam UMC, University of Amsterdam, 1105 AZ, The Netherlands. · Department of Pharmaceutics, Jiaxing University Medical College, Jiaxing 314001, Zhejiang, China. · Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, 3584 CG, The Netherlands. · Department of Pathology, Amsterdam UMC, University of Amsterdam, 1105 AZ, The Netherlands. · Cancer Pharmacology Lab, AIRC Start-Up Unit, Fondazione Pisana per la Scienza onlus, 56017 Pisa, Italy. · Department of Neurosurgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands. · Medical Oncology Unit, University Hospital of Parma, 43 126 Parma, Italy. · Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands. · Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, 1081 HV, The Netherlands. e.giovannetti@amsterdamumc.nl. · Cancer Pharmacology Lab, AIRC Start-Up Unit, Fondazione Pisana per la Scienza onlus, 56017 Pisa, Italy. e.giovannetti@amsterdamumc.nl. ·Cancers (Basel) · Pubmed #31443224.

ABSTRACT: Accurate diagnosis of pancreatic head lesions remains challenging as no minimally invasive biomarkers are available to discriminate distal cholangiocarcinoma (CCA) from pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to identify specific circulating microRNAs (miRNAs) to diagnose distal CCA. In the discovery phase, PCR profiling of 752 miRNAs was performed on fourteen patients with distal CCA and age- and sex-matched healthy controls. Candidate miRNAs were selected for evaluation and validation by RT-qPCR in an independent cohort of distal CCA (

8 Article Proteomic analysis of gemcitabine-resistant pancreatic cancer cells reveals that microtubule-associated protein 2 upregulation associates with taxane treatment. 2019

Le Large, Tessa Ya Sung / El Hassouni, Btissame / Funel, Niccola / Kok, Bart / Piersma, Sander R / Pham, Thang V / Olive, Kenneth P / Kazemier, Geert / van Laarhoven, Hanneke W M / Jimenez, Connie R / Bijlsma, Maarten F / Giovannetti, Elisa. ·Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, NetherlandsLEXOR, Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, NetherlandsCancer Pharmacology Lab, AIRC-Start-Up, University Hospital of Pisa, Pisa, Italy. · Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands. · Cancer Pharmacology Lab, AIRC-Start-Up, University Hospital of Pisa, Pisa, Italy. · Surgery, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands. · Departments of Medicine and Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York City, NY, USA. · Medical Oncology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands. · LEXOR, Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands. · Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, Netherlands. ·Ther Adv Med Oncol · Pubmed #31205498.

ABSTRACT: Background: Chemoresistance hampers the treatment of patients suffering from pancreatic ductal adenocarcinoma (PDAC). Here we aimed to evaluate the (phospho)proteome of gemcitabine-sensitive and gemcitabine-resistant PDAC cells to identify novel therapeutic targets and predictive biomarkers. Methods: The oncogenic capabilities of gemcitabine-sensitive and resistant PDAC cells were evaluated Results: Gemcitabine-resistant cells had increased potential to induce xenograft tumours ( Conclusions: These data show an explanation as to why the combination of gemcitabine with nab-paclitaxel is effective in PDAC patients. The identified gemcitabine-resistance marker, MAP2, emerged as a novel prognostic marker in PDAC patients treated with gemcitabine and warrants further clinical investigation.

9 Article Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study. 2018

Sallinen, Ville J / Le Large, Tessa Y S / Tieftrunk, Elke / Galeev, Shamil / Kovalenko, Zahar / Haugvik, Sven-Petter / Antila, Anne / Franklin, Oskar / Martinez-Moneo, Emma / Robinson, Stuart M / Panzuto, Francesco / Regenet, Nicolas / Muffatti, Francesca / Partelli, Stefano / Wiese, Dominik / Ruszniewski, Philippe / Dousset, Bertrand / Edwin, Bjørn / Bartsch, Detlef K / Sauvanet, Alain / Falconi, Massimo / Ceyhan, Güralp O / Gaujoux, Sebastien / Anonymous100922. ·Department of Abdominal Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Department of Transplantation and Liver Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland. Electronic address: ville.salinen@helsinki.fi. · Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany. · General Surgery Department, Saint Luke's Clinical Hospital, Saint Petersburg, Russia. · Federal Medical and Rehabilitation Center, Department of Surgical Oncology, Moscow, Russia. · The Intervention Center, Oslo University Hospital, Oslo, Norway; Department of Surgery, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway. · Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland. · Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden. · Gastroenterology Department, Hospital Universitario Cruces, Barakaldo, Bizkaia, Spain. · Department of HPB Surgery, Freeman Hospital, Newcastle Upon Tyne, UK. · Digestive and Liver Disease Unit, Sant'Andrea Hospital - Sapienza University of Rome, Italy. · Department of Digestive and Endocrine Surgery, Institut des Maladies Digestives (IMAD), Nantes 44093, France. · Chirurgia Del Pancreas, Chirurgia Del Pancreas, Pancreas Translational & Clinical Research Center, Università Vita e Salute, Ospedale San Raffaele IRCC, Milano, Italy. · Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany. · Department of Gastroenterology, Pôle des Maladies de L'Appareil Digestif (PMAD), DHU Unity, Clichy 92110, France; Université Paris Diderot, Paris, France. · Department of Digestive, Pancreatic and Endocrine Surgery, Cochin Hospital, APHP, Paris, France; Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. · The Intervention Center, Oslo University Hospital, Oslo, Norway; Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Université Paris Diderot, Paris, France; AP-HP, Hôpital Beaujon, Department of Hepato-Pancreato-Biliary Surgery, Pôle des Maladies de L'Appareil Digestif (PMAD), DHU Unity, University Paris VII, AP-HP, Hôpital Beaujon, Clichy 92110, France. ·HPB (Oxford) · Pubmed #28988702.

ABSTRACT: BACKGROUND: Malignant potential of small (≤20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs. METHODS: Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses. RESULTS: sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized ≤10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively. CONCLUSIONS: In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.

10 Article The Role of MicroRNAs in Resistance to Current Pancreatic Cancer Treatment: Translational Studies and Basic Protocols for Extraction and PCR Analysis. 2016

Garajová, Ingrid / Le Large, Tessa Y S / Giovannetti, Elisa / Kazemier, Geert / Biasco, Guido / Peters, Godefridus J. ·Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, CCA 1.42, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands. · Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy. · Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, CCA 1.42, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands. gj.peters@vumc.nl. ·Methods Mol Biol · Pubmed #26910074.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a common cause of cancer death and has the worst prognosis of any major malignancy, with less than 5 % of patients alive 5-years after diagnosis. The therapeutic options for metastatic PDAC have changed in the past few years from single agent gemcitabine treatment to combination regimens. Nowadays, FOLFIRINOX or gemcitabine with nab-paclitaxel are new standard combinations in frontline metastatic setting in PDAC patients with good performance status. MicroRNAs (miRNA) are small, noncoding RNA molecules affecting important cellular processes such as inhibition of apoptosis, cell proliferation, epithelial-to-mesenchymal transition (EMT), metastases, and resistance to common cytotoxic and anti-signaling therapy in PDAC. A functional association between miRNAs and chemoresistance has been described for several common therapies. Therefore, in this review, we summarize the current knowledge on the role of miRNAs in the resistance to current anticancer treatment used for patients affected by metastatic PDAC.

11 Article Circulating microRNAs as diagnostic biomarkers for pancreatic cancer. 2015

Le Large, Tessa Y S / Meijer, Laura L / Prado, Mireia Mato / Kazemier, Geert / Frampton, Adam E / Giovannetti, Elisa. ·a Department of Surgery , VU University Medical Center , Amsterdam , the Netherlands. · b Department of Medical Oncology , VU University Medical Center , Amsterdam , the Netherlands. · c Division of Oncology, Department of Surgery & Cancer , Imperial Centre for Translational and Experimental Medicine (ICTEM), Imperial College, Hammersmith Hospital Campus , London , UK. · d HPB Surgical Unit, Department of Surgery & Cancer , Imperial College, Hammersmith Hospital Campus , London , UK. · e Cancer Pharmacology Lab, AIRC Start-Up Unit , University of Pisa , Pisa , Italy. ·Expert Rev Mol Diagn · Pubmed #26567751.

ABSTRACT: There is an urgent need for novel and reliable biomarkers for the diagnosis and prognostication of pancreatic ductal adenocarcinoma (PDAC). Circulating microRNAs (miRNAs) have been extensively profiled in PDAC blood samples, but few studies have performed adequate validation of candidate markers. The evaluated study by Xu et al. investigated pre-operative plasma miRNAs from PDAC patients over three phases and three surgical centers. They revealed miR-486-5p and miR-938 were able to discriminate PDAC patients from healthy controls and those with chronic pancreatitis. The diagnostic ability of miR-486-5p for identifying PDAC from healthy controls was comparable to that of CA 19-9. This study provides further evidence for the use of blood-based miRNAs as diagnostic biomarkers in PDAC. However, as these have not been identified in previous studies these require further validation and methodology needs to be standardized if these are ever to be used in the clinic.

12 Article AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients. 2014

Avan, Abolfazl / Avan, Amir / Le Large, Tessa Y S / Mambrini, Andrea / Funel, Niccola / Maftouh, Mina / Ghayour-Mobarhan, Majid / Cantore, Maurizio / Boggi, Ugo / Peters, Godefridus J / Pacetti, Paola / Giovannetti, Elisa. ·Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. · Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Biochemistry of Nutrition Research Center, and Department of New Sciences and Technology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. · Department of Medical Oncology, Carrara Civic Hospital, Carrara, Italy. · Start-Up Unit, University of Pisa, Pisa, Italy. · Biochemistry of Nutrition Research Center, and Department of New Sciences and Technology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. · Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands; Start-Up Unit, University of Pisa, Pisa, Italy. ·PLoS One · Pubmed #25238546.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a substantial impact on clinical management. Here we investigated the prognostic value and association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia in PDAC. Genotyping was performed in DNA from blood samples of a test and validation cohorts of 151 and 152 chemo-naive locally-advanced/metastatic PDAC patients, respectively. The association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia as well as the correlation between cachexia and the candidate polymorphisms and overall survival were analyzed. Akt expression and phosphorylation in muscle biopsies were evaluated by specific ELISA assays. SELP-rs6136-AA and AKT1-rs1130233-AA/GA genotypes were associated with increased risk of developing cachexia in both cohorts (SELP: p = 0.011 and p = 0.045; AKT1: p = 0.004 and p = 0.019 for the first and second cohorts, respectively), while patients carrying AKT1-rs1130233-GG survived significantly longer (p = 0.002 and p = 0.004 for the first and second cohorts, respectively). In the multivariate analysis AKT1-rs1130233-AA/GA genotypes were significant predictors for shorter survival, with an increased risk of death of 1.7 (p = 0.002) and 1.6 (p = 0.004), in the first and second cohorts, respectively. This might be explained by the reduced phosphorylation of Akt1 in muscle biopsies from patients harboring AKT1-rs1130233-AA/GA (p = 0.003), favoring apoptosis induction. In conclusion, SELP and AKT1 polymorphisms may play a role in the risk of cachexia and death in PDAC patients, and should be further evaluated in larger prospective studies.

13 Minor Usefulness of Measuring microRNAs in Bile and Plasma for Pancreatic Ductal Adenocarcinoma Diagnosis. 2015

Le Large, Tessa Y S / Frampton, Adam E / Meijer, Laura L / Stebbing, Justin / Kazemier, Geert / Giovannetti, Elisa. ·1] Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands [2] Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands. · Department of Surgery and Cancer, Imperial College, London, UK. · Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands. · 1] Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands [2] AIRC Start-Up Unit, University of Pisa, Pisa, Italy. ·Am J Gastroenterol · Pubmed #25942302.

ABSTRACT: -- No abstract --