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Pancreatic Neoplasms: HELP
Articles by Paola Spaggiari
Based on 11 articles published since 2010
(Why 11 articles?)
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Between 2010 and 2020, Paola Spaggiari wrote the following 11 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Regorafenib in patients with refractory metastatic pancreatic cancer: a Phase II study (RESOUND). 2019

Bozzarelli, Silvia / Rimassa, Lorenza / Giordano, Laura / Sala, Simona / Tronconi, Maria Chiara / Pressiani, Tiziana / Smiroldo, Valeria / Prete, Maria G / Spaggiari, Paola / Personeni, Nicola / Santoro, Armando. ·Medical Oncology & Hematology Unit, Humanitas Cancer Center, Humanitas Clinical & Research Center, IRCCS, Rozzano, Milan, 20089, Italy. · Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, 20090, Italy. · Biostatistics Unit, Humanitas Cancer Center, Humanitas Clinical & Research Center, IRCCS, Rozzano, Milan, 20089, Italy. · Anatomic Pathology Unit, Humanitas Clinical & Research Center, IRCCS, Rozzano, Milan, 20089, Italy. ·Future Oncol · Pubmed #31746632.

ABSTRACT:

2 Article FOXA2 controls the cis-regulatory networks of pancreatic cancer cells in a differentiation grade-specific manner. 2019

Milan, Marta / Balestrieri, Chiara / Alfarano, Gabriele / Polletti, Sara / Prosperini, Elena / Spaggiari, Paola / Zerbi, Alessandro / Diaferia, Giuseppe R / Natoli, Gioacchino. ·Humanitas University, Milano, Italy. · Humanitas Clinical Research Center IRCCS, Milano, Italy. · Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milano, Italy. ·EMBO J · Pubmed #31531882.

ABSTRACT: Differentiation of normal and tumor cells is controlled by regulatory networks enforced by lineage-determining transcription factors (TFs). Among them, TFs such as FOXA1/2 bind naïve chromatin and induce its accessibility, thus establishing new gene regulatory networks. Pancreatic ductal adenocarcinoma (PDAC) is characterized by the coexistence of well- and poorly differentiated cells at all stages of disease. How the transcriptional networks determining such massive cellular heterogeneity are established remains to be determined. We found that FOXA2, a TF controlling pancreas specification, broadly contributed to the cis-regulatory networks of PDACs. Despite being expressed in both well- and poorly differentiated PDAC cells, FOXA2 displayed extensively different genomic distributions and controlled distinct gene expression programs. Grade-specific functions of FOXA2 depended on its partnership with TFs whose expression varied depending on the differentiation grade. These data suggest that FOXA2 contributes to the regulatory networks of heterogeneous PDAC cells via interactions with alternative partner TFs.

3 Article Pancreatic Neuroendocrine Tumours: The Role of Endoscopic Ultrasound Biopsy in Diagnosis and Grading Based on the WHO 2017 Classification. 2019

Di Leo, Milena / Poliani, Laura / Rahal, Daoud / Auriemma, Francesco / Anderloni, Andrea / Ridolfi, Cristina / Spaggiari, Paola / Capretti, Giovanni / Di Tommaso, Luca / Preatoni, Paoletta / Zerbi, Alessandro / Carnaghi, Carlo / Lania, Andrea / Malesci, Alberto / Repici, Alessandro / Carrara, Silvia. ·Humanitas Clinical and Research Center, IRCCS, Digestive Endoscopy Unit, Division of Gastroenterology, Milan, Italy, milena.di_leo@hunimed.eu. · Humanitas University, Department of Biomedical Sciences, Milan, Italy, milena.di_leo@hunimed.eu. · Humanitas Clinical and Research Center, IRCCS, Digestive Endoscopy Unit, Division of Gastroenterology, Milan, Italy. · Department of Pathology, Humanitas Clinical and Research Center, IRCCS, Milan, Italy. · Humanitas Clinical and Research Center, IRCCS, Pancreatic Surgery Unit, Milan, Italy. · Humanitas University, Department of Biomedical Sciences, Milan, Italy. · Humanitas Clinical and Research Center, IRCCS, Division of Gastroenterology, Milan, Italy. · Humanitas Clinical and Research Center, IRCCS, Division of Oncology, Milan, Italy. · Humanitas Clinical and Research Center, IRCCS, Division of Endocrinology, Milan, Italy. ·Dig Dis · Pubmed #30897588.

ABSTRACT: BACKGROUND: One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour. OBJECTIVES: The aim of the study was to evaluate the role of endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center. METHODS: A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading. RESULTS: The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%. CONCLUSION: EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.

4 Article Ki-67 and presence of liver metastases identify different progression-risk classes in pancreatic neuroendocrine neoplasms (pNEN) undergoing resection. 2019

Milione, Massimo / Maisonneuve, Patrick / Pellegrinelli, Alessio / Spaggiari, Paola / Centonze, Giovanni / Coppa, Jorgelina / Delconte, Gabriele / Droz Dit Busset, Michele / Lanhazo, Oleksandra / Pruneri, Giancarlo / Mazzaferro, Vincenzo. ·Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy. · Department of Pathology, Cancer Center Humanitas Research Hospital, Rozzano Milan, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Endoscopy, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy. Electronic address: michele.drozditbusset@istitutotumori.mi.it. · Department of Surgery, Transcarpathian Regional Hospital, Užhorod, Ukraine. · Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; University of Milan, School of Medicine, Italy. · Surgery and Neuroendocrine Tumor Group, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; University of Milan, School of Medicine, Italy. ·Eur J Surg Oncol · Pubmed #30366875.

ABSTRACT: In pancreatic neuroendocrine neoplasms (pNEN), size ≤2 cm and Ki-67 < 3% suggest indolent behavior, but no factor alone predicts prognosis. We investigated factors predictive of tumor progression in 80 pNENs surgically resected in a single Institution from 1995 to 2015. At multivariable analysis the only two independent variables related to PFS were Ki-67 (HR 2.97; 95%CI 1.26-7.02) and presence of synchronous liver metastases (HR 3.60; 95%CI 1.70-7.61). Using Ki-67 < 3% and M0 as reference, the HR for tumor progression was 3.21 (95%CI 1.18-8.74) for M0 patients with Ki-67 3-20%, 5.06 (2.29-11.2) for M1 patients with Ki-67 ≤ 20% and 24.3 (6.64-89.2) for those with Ki-67 > 20%. Tumor size (≤2 vs. >2 cm) was not a predictive factor at any analysis. Intra-class correlation of Ki-67 values on pre-surgical biopsies vs. surgical specimens was 0.99 and Ki-67 classes were correctly identified in 97% of biopsies. Ki-67 and presence of liver metastases are the major prognostic factors in pNEN and identify different progression risks regardless of tumor size. Pre-surgical pNEN biopsy for Ki-67 assessment should be included in the evaluation of patients with 1-2 cm tumors to help in the decision on whether to perform surgical resection.

5 Article Competitive Testing of the WHO 2010 versus the WHO 2017 Grading of Pancreatic Neuroendocrine Neoplasms: Data from a Large International Cohort Study. 2018

Rindi, Guido / Klersy, Catherine / Albarello, Luca / Baudin, Eric / Bianchi, Antonio / Buchler, Markus W / Caplin, Martyn / Couvelard, Anne / Cros, Jérôme / de Herder, Wouter W / Delle Fave, Gianfranco / Doglioni, Claudio / Federspiel, Birgitte / Fischer, Lars / Fusai, Giuseppe / Gavazzi, Francesca / Hansen, Carsten P / Inzani, Frediano / Jann, Henning / Komminoth, Paul / Knigge, Ulrich P / Landoni, Luca / La Rosa, Stefano / Lawlor, Rita T / Luong, Tu V / Marinoni, Ilaria / Panzuto, F / Pape, Ulrich-Frank / Partelli, Stefano / Perren, Aurel / Rinzivillo, Maria / Rubini, Corrado / Ruszniewski, Philippe / Scarpa, Aldo / Schmitt, Anja / Schinzari, Giovanni / Scoazec, Jean-Yves / Sessa, Fausto / Solcia, Enrico / Spaggiari, Paola / Toumpanakis, Christos / Vanoli, Alessandro / Wiedenmann, Bertram / Zamboni, Giuseppe / Zandee, Wouter T / Zerbi, Alessandro / Falconi, Massimo. ·Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italyguido.rindi@unicatt.it. · Service of Biometry and Clinical Epidemiology, Research Department, and IRCCS Fondazione Policlinico San Matteo, Pavia, Italy. · Pathology Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Oncology, Cancer Campus, Villejuif, France. · Department of Endocrinology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Surgery, University Hospital Heidelberg, Neu Heidelberg, Germany. · Neuroendocrine Tumour Unit, Centre for Gastroenterology, London, United Kingdom. · Department of Pathology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Section Endocrinology, Department of Internal Medicine, Erasmus University Medical Center and and Erasmus MC Cancer Institute Rotterdam, Rotterdam ENETS Center of Excellence, Rotterdam, The Netherlands. · Digestive and Liver Disease Unit, Sant'Andrea University Hospital, Roma ENETS Center of Excellence, Rome, Italy. · Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Department of Surgery, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Pancreatic Surgery, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen ENETS Center of Excellence, Copenhagen, Denmark. · Institute of Pathology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Hepatology and Gastroenterology, Charité, Campus Virchow Klinikum and Charite Mitte, University Medicine Berlin, Berlin ENETS Center of Excellence, Berlin, Germany. · Institute of Pathology, Stadtspital Triemli, Zurich, Switzerland. · Department of Surgery and Oncology, General and Pancreatic Surgery, The Pancreas Institute, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, Ospedale di Circolo, Università dell'Insubria, Varese, Italy. · Section of Pathology and ARC-Net Research Centre, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona ENETS Center of Excellence, Verona, Italy. · Department of Pathology, University College, Royal Free Hospital, London ENETS Center of Excellence, London, United Kingdom. · Institute of Pathology, University of Bern, Bern, Switzerland. · Pancreatic Surgery Unit, San Raffaele Scientific Institute, Milan, Italy. · Department of Pathology, Marche Polytechnic University, Ancona, Italy. · Department of Gastroenterology and Pancreatology, Hopital Beaujon, Paris ENETS Center of Excellence, Clichy, France. · Department of Medical Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma-Università Cattolica del Sacro Cuore, Roma ENETS Center of Excellence, Rome, Italy. · Department of Medical Biology and Pathology, Cancer Campus, Villejuif, France. · Department of Molecular Medicine, University of Pavia, Pavia, Italy. · Pathology Department, Humanitas Clinical and Research Center, Humanitas Milan ENETS Center of Excellence, Milan, Italy. · Department of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy. ·Neuroendocrinology · Pubmed #30300897.

ABSTRACT: BACKGROUND: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). OBJECTIVES: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. METHOD: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell's C statistics, and Royston's explained variation in univariable and multivariable analyses. RESULTS: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. CONCLUSIONS: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

6 Article Direct per-oral pancreatoscopy as a diagnostic tool for intraductal papillary mucinous neoplasm. 2018

Anderloni, Andrea / Fugazza, Alessandro / Troncone, Edoardo / Carrara, Silvia / Rovati, Andrea / Spaggiari, Paola / Repici, Alessandro. ·Digestive Endoscopy Unit, Humanitas Research Hospital, Rozzano, Milan,Italy. andrea.anderloni@humanitas.it. · Digestive Endoscopy Unit, Humanitas Research Hospital, Rozzano, Milan,Italy. · Oncology Unit, Ospedale Maggiore di Lodi, Lodi,Italy. · Department of Pathology, Humanitas Research Hospital, Rozzano, Milan, Italy. · Digestive Endoscopy Unit, Humanitas Research Hospital, Rozzano, Milan;Humanitas University, Rozzano, Milan, Italy. ·J Gastrointestin Liver Dis · Pubmed #30240462.

ABSTRACT: -- No abstract --

7 Article Rectal metastases from malignant mucinous cystic neoplasm of the pancreas mimicking a rectal carcinoma. 2018

Carrara, Silvia / Di Leo, Milena / Spaggiari, Paola / Bagnoli, Pietro Francesco / Repici, Alessandro. ·Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center, Humanitas University, Milan, Italy. · Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Clinical and Research Center, Department of Biomedical Sciences, Humanitas University, Milan, Italy. · Department of Pathology, Humanitas Clinical and Research Center, Humanitas University, Milan, Italy. · Department of Cancer Surgery, Humanitas Clinical and Research Center, Humanitas University, Milan, Italy. ·Gastrointest Endosc · Pubmed #28673644.

ABSTRACT: -- No abstract --

8 Article The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: Morphological Differentiation and Proliferation Identify Different Prognostic Categories. 2017

Milione, Massimo / Maisonneuve, Patrick / Spada, Francesca / Pellegrinelli, Alessio / Spaggiari, Paola / Albarello, Luca / Pisa, Eleonora / Barberis, Massimo / Vanoli, Alessandro / Buzzoni, Roberto / Pusceddu, Sara / Concas, Laura / Sessa, Fausto / Solcia, Enrico / Capella, Carlo / Fazio, Nicola / La Rosa, Stefano. ·Anatomic Pathology, Department of Pathology and Laboratory Medicine, IRCCS Foundation National Cancer Institute, Milan, Italy. ·Neuroendocrinology · Pubmed #26943788.

ABSTRACT: BACKGROUND/AIMS: Gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) are defined as neuroendocrine neoplasms (NENs) with a Ki-67 index >20% according to the 2010 WHO classification. Some reports suggest that this category is heterogeneous. We retrospectively studied a series of 136 patients affected by grade 3 GEP-NECs with the aim to clarify the prognostic role of tumor morphological differentiation, proliferation, defect in mismatch repair proteins (MMRd), CD117 expression, and site of origin. The primary endpoint was the correlation between these parameters and the overall survival (OS). METHODS: Univariate and multivariable Cox proportional hazards regression analyses were used to assess the prognostic significance of various clinical and histopathologic features. RESULTS: With a median follow-up of 81 months, the median OS was 12.9 months. At multivariate analysis, morphological differentiation, Ki-67 index, MMRd, stage, and CD117 expression were independent prognostic markers in NECs. Three different prognostic categories of NECs were identified according to the degree of morphologic differentiation (well vs. poorly differentiated) and Ki-67 index (<55% vs. ≥55%). On this basis, median OS was 43.6 months in well-differentiated neoplasms with a Ki-67 index 20-55% (named type A), 24.5 months in poorly differentiated neoplasms with a Ki-67 index 20-55% (type B), and 5.3 months (p < 0.0001) in poorly differentiated neoplasms with a Ki-67 index ≥55% (type C). CONCLUSIONS: The present study suggests that GEP-NECs represent a heterogeneous group of neoplasms which can be better classified in different prognostic categories using both tumor morphology and Ki-67 index.

9 Article Dissection of transcriptional and cis-regulatory control of differentiation in human pancreatic cancer. 2016

Diaferia, Giuseppe R / Balestrieri, Chiara / Prosperini, Elena / Nicoli, Paola / Spaggiari, Paola / Zerbi, Alessandro / Natoli, Gioacchino. ·Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy. · Division of Pancreatic Surgery, Humanitas Clinical Institute, Milan, Italy. · Department of Experimental Oncology, European Institute of Oncology (IEO), Milan, Italy gioacchino.natoli@ieo.eu. ·EMBO J · Pubmed #26769127.

ABSTRACT: The histological grade of carcinomas describes the ability of tumor cells to organize in differentiated epithelial structures and has prognostic and therapeutic impact. Here, we show that differential usage of the genomic repertoire of transcriptional enhancers leads to grade-specific gene expression programs in human pancreatic ductal adenocarcinoma (PDAC). By integrating gene expression profiling, epigenomic footprinting, and loss-of-function experiments in PDAC cell lines of different grade, we identified the repertoires of enhancers specific to high- and low-grade PDACs and the cognate set of transcription factors acting to maintain their activity. Among the candidate regulators of PDAC differentiation, KLF5 was selectively expressed in pre-neoplastic lesions and low-grade primary PDACs and cell lines, where it maintained the acetylation of grade-specific enhancers, the expression of epithelial genes such as keratins and mucins, and the ability to organize glandular epithelia in xenografts. The identification of the transcription factors controlling differentiation in PDACs will help clarify the molecular bases of its heterogeneity and progression.

10 Article A Bone in the Pancreas. 2016

Carrara, Silvia / Spaggiari, Paola / Zerbi, Alessandro. ·Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas Research Hospital, Rozzano Milan, Italy. · Department of Pathology, Humanitas Research Hospital, Rozzano Milan, Italy. · Pancreatic Surgery Unit, Humanitas Research Hospital, Rozzano Milan, Italy. ·Gastroenterology · Pubmed #26718169.

ABSTRACT: -- No abstract --

11 Article Morphohistological features of pancreatic stump are the main determinant of pancreatic fistula after pancreatoduodenectomy. 2014

Ridolfi, Cristina / Angiolini, Maria Rachele / Gavazzi, Francesca / Spaggiari, Paola / Tinti, Maria Carla / Uccelli, Fara / Madonini, Marco / Montorsi, Marco / Zerbi, Alessandro. ·Section of Pancreatic Surgery, Department of General Surgery, Humanitas Research Hospital, University of Milan School of Medicine, Via Manzoni 56, Rozzano, 20089 Milan, Italy. · Department of Pathology, Humanitas Research Hospital, Rozzano, 20089 Milan, Italy. ·Biomed Res Int · Pubmed #24900974.

ABSTRACT: INTRODUCTION: Pancreatic surgery is challenging and associated with high morbidity, mainly represented by postoperative pancreatic fistula (POPF) and its further consequences. Identification of risk factors for POPF is essential for proper postoperative management. AIM OF THE STUDY: Evaluation of the role of morphological and histological features of pancreatic stump, other than main pancreatic duct diameter and glandular texture, in POPF occurrence after pancreaticoduodenectomy. PATIENTS AND METHODS: Between March 2011 and April 2013, we performed 145 consecutive pancreaticoduodenectomies. We intraoperatively recorded morphological features of pancreatic stump and collected data about postoperative morbidity. Our dedicated pathologist designed a score to quantify fibrosis and inflammation of pancreatic tissue. RESULTS: Overall morbidity was 59,3%. Mortality was 4,1%. POPF rate was 28,3%, while clinically significant POPF were 15,8%. Male sex (P = 0.009), BMI ≥ 25 (P = 0.002), prolonged surgery (P = 0.001), soft pancreatic texture (P < 0.001), small pancreatic duct (P < 0.001), pancreatic duct decentralization on stump anteroposterior axis, especially if close to the posterior margin (P = 0.031), large stump area (P = 0.001), and extended stump mobilization (P = 0.001) were related to higher POPF rate. Our fibrosis-and-inflammation score is strongly associated with POPF (P = 0.001). DISCUSSION AND CONCLUSIONS: Pancreatic stump features evaluation, including histology, can help the surgeon in fitting postoperative management to patient individual risk after pancreaticoduodenectomy.