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Pancreatic Neoplasms: HELP
Articles by Francesca Muffatti
Based on 19 articles published since 2010
(Why 19 articles?)
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Between 2010 and 2020, F. Muffatti wrote the following 19 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Treatment challenges in and outside a specialist network setting: Pancreatic neuroendocrine tumours. 2019

Lykoudis, Panagis M / Partelli, Stefano / Muffatti, Francesca / Caplin, Martyn / Falconi, Massimo / Fusai, Giuseppe K / Anonymous4960926. ·Department of Hepato-Pancreato-Biliary Surgery & Liver Transplantation, Royal Free Hospital, London, UK. Electronic address: p.lykoudis@ucl.ac.uk. · Pancreatic Surgery Unit, Pancreas Translational & Research Institute, Scientific Institute San Raffaele Hospital & University "Vita e Salute", Milan, Italy. · Department of Gastroenterology and G.I. & Tumour Neuroendocrinology, Royal Free Hospital, London, UK. · Department of Hepato-Pancreato-Biliary Surgery & Liver Transplantation, Royal Free Hospital, London, UK. ·Eur J Surg Oncol · Pubmed #29126671.

ABSTRACT: Pancreatic Neuroendocrine Neoplasms comprise a group of rare tumours with special biology, an often indolent behaviour and particular diagnostic and therapeutic requirements. The specialized biochemical tests and radiological investigations, the complexity of surgical options and the variety of medical treatments that require individual tailoring, mandate a multidisciplinary approach that can be optimally achieved through an organized network. The present study describes currents concepts in the management of these tumours as well as an insight into the challenges of delivering the pathway in and outside a Network.

2 Review How should incidental NEN of the pancreas and gastrointestinal tract be followed? 2018

Ariotti, Riccardo / Partelli, Stefano / Muffatti, Francesca / Andreasi, Valentina / Della Sala, Francesca / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Via Olgettina 60, 20132, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Via Olgettina 60, 20132, Milan, Italy. falconi.massimo@hsr.it. ·Rev Endocr Metab Disord · Pubmed #29527619.

ABSTRACT: Neuroendocrine gastro-entero-pancreatic neoplasms (GEP-NENs) constitute a heterogeneous group of tumors, whose incidence has increased over the years. The most frequent site for primary disease is the stomach followed by small and large intestine, and pancreas. In the last decade, a dramatic growing in the incidence of small, incidental GEP-NENs has been recorded. In parallel, an increasing attitude toward more conservative approaches instead of surgical management has being widely spreading. This is particularly true for small, asymptomatic, pancreatic NEN as for these tumor forms an active surveillance has proven to be safe and feasible. Primary site and biological features of the neoplasms lead to different strategies and indications for surveillance and follow-up. This review focuses on the current evidence on modality and timing of surveillance and conservative treatment of incidentally discovered lesions.

3 Review Systematic review and meta-analysis on laparoscopic pancreatic resections for neuroendocrine neoplasms (PNENs). 2017

Tamburrino, Domenico / Partelli, Stefano / Renzi, Claudio / Crippa, Stefano / Muffatti, Francesca / Perali, Carolina / Parisi, Amilcare / Randolph, Justus / Fusai, Giuseppe Kito / Cirocchi, Roberto / Falconi, Massimo. ·a HPB and Liver Transplant Surgery , Royal Free Hospital, NHS Foundation Trust , London , UK. · b Pancreatic surgery Unit, Pancreas Translational & Clinical Research Center - IRCCS San Raffaele Scientific Institute , 'Vita e Salute' University , Milan , Italy. · c Department of General and Oncologic Surgery , University of Perugia, St. Mary's Hospital , Terni , Italy. · d Department of Digestive Surgery , University of Perugia, St. Mary's Hospital , Terni , Italy. · e Tift College of Education , Mercer University , Atlanta , GA , USA. ·Expert Rev Gastroenterol Hepatol · Pubmed #27781493.

ABSTRACT: INTRODUCTION: The safety of laparoscopic resections (LPS) of pancreatic neuroendocrine neoplasms (PNENs) has been well established in the literature. Areas covered: Studies conducted between January 2003 and December 2015 that reported on LPS and open surgery (OPS) were reviewed. The primary outcomes were the rate of post-operative complications and the length of hospital stay (LoS) after laparoscopic and open surgical resection. The rate of recurrence was the secondary outcome. Eleven studies were included with a total of 907 pancreatic resections for PNENs, of whom, 298 (32.8%) underwent LPS and 609 (67.2%) underwent open surgery. LPS resulted in a significantly shorter LoS (p < 0.0001) and lower blood loss (p < 0.0001). The meta-analysis did not show any significant difference in the pancreatic fistula rate, recurrence rate or post-operative mortality between the two groups. Expert commentary: LPS is a safe approach even for PNENs and it is associated with a shorter LoS.

4 Review Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology. 2016

Crippa, Stefano / Partelli, Stefano / Belfiori, Giulio / Palucci, Marco / Muffatti, Francesca / Adamenko, Olga / Cardinali, Luca / Doglioni, Claudio / Zamboni, Giuseppe / Falconi, Massimo. ·Stefano Crippa, Stefano Partelli, Marco Palucci, Francesca Muffatti, Olga Adamenko, Massimo Falconi, Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, 20132 Milan, Italy. ·World J Gastroenterol · Pubmed #28018101.

ABSTRACT: Neuroendocrine carcinomas (NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.

5 Review Systematic review and meta-analysis of metal versus plastic stents for preoperative biliary drainage in resectable periampullary or pancreatic head tumors. 2016

Crippa, S / Cirocchi, R / Partelli, S / Petrone, M C / Muffatti, F / Renzi, C / Falconi, M / Arcidiacono, P G. ·Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy. · Department of General and Oncologic Surgery, University of Perugia, St. Maria Hospital, Terni, Italy. · Division of Pancreato-Biliary Endoscopy and Endoscopic Ultrasound, San Raffaele Scientific Institute, Milan, Italy. · Department of General and Oncologic Surgery, University of Perugia, Perugia, Italy. · Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #27296728.

ABSTRACT: BACKGROUND: Preoperative biliary drainage (PBD) with stenting increases complications compared with surgery without PBD. Metallic stents are considered superior to plastic stents when considering stent-related complications. Aim of the present systematic review and meta-analysis is to compare the rate of endoscopic re-intervention before surgery and postoperative outcomes of metal versus plastic stents in patients with resectable periampullary or pancreatic head neoplasms. METHODS: We conducted a bibliographic research using the National Library of Medicine's PubMed database, including both randomized controlled trials (RCTs) and non-RCTs. Quantitative synthesis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Statistical heterogeneity was assessed using the I(2) tests. RESULTS: One RCT and four non-RCTs were selected, including 704 patients. Of these, 202 patients (29.5%) were treated with metal stents and 502 (70.5%) with plastic stents. The majority of patients (86.4%) had pancreatic cancer. The rate of endoscopic re-intervention after preoperative biliary drainage was significantly lower in the metal stent (3.4%) than in the plastic stent (14.8%) group (p < 0.0001). The rate of postoperative pancreatic fistula was significantly lower in the meta stent group as well (5.1% versus 11.8%, p = 0.04). The rate of post-operative surgical complications and of - post-operative mortality did not differ between the two groups. CONCLUSIONS: Although the present systematic review and meta-analysis demonstrates that metal stent are more effective than plastic stents for PBD in patients with resectable periampullary tumors, randomized controlled trials are needed in order to confirm these data with a higher level of evidence.

6 Review Surgical management of neuroendocrine tumors. 2016

Tamburrino, Domenico / Spoletini, Gabriele / Partelli, Stefano / Muffatti, Francesca / Adamenko, Olga / Crippa, Stefano / Falconi, Massimo. ·HPB and Liver Transplant Surgery, Royal Free Hospital, NHS Foundation Trust, London Pond Street NW3 2QG, London, UK. Electronic address: m_tamburrino@hotmail.com. · HPB and Liver Transplant Surgery, Royal Free Hospital, NHS Foundation Trust, London Pond Street NW3 2QG, London, UK. Electronic address: gabriele.spoletini@gmail.com. · Pancreatic Surgery Unit, "Vita e Salute" University, San Raffaele Hospital, Olgettina n. 60 e n. 48, 20132 Milan, Italy. Electronic address: partelli.stefano@hsr.it. · Pancreatic Surgery Unit, "Vita e Salute" University, San Raffaele Hospital, Olgettina n. 60 e n. 48, 20132 Milan, Italy. Electronic address: muffatti.francesca@hsr.it. · Pancreatic Surgery Unit, "Vita e Salute" University, San Raffaele Hospital, Olgettina n. 60 e n. 48, 20132 Milan, Italy. Electronic address: adamenko.olga@hsr.it. · Pancreatic Surgery Unit, "Vita e Salute" University, San Raffaele Hospital, Olgettina n. 60 e n. 48, 20132 Milan, Italy. Electronic address: crippa1.stefano@hsr.it. · Pancreatic Surgery Unit, "Vita e Salute" University, San Raffaele Hospital, Olgettina n. 60 e n. 48, 20132 Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Best Pract Res Clin Endocrinol Metab · Pubmed #26971846.

ABSTRACT: During the last decades an increase in the incidence of neuroendocrine tumors (NETs) was observed. Gastroenteropancreatic NETs represent the majority of NETs. Compared with their epithelial counterpart they usually have a more indolent behaviour and surgical resection improves survival. Tumor diameter is one of the main parameter in the decision making process for nonfunctioning forms. Generally, small lesions can be treated conservatively whereas larger tumors should be treated with standard surgical resection and lymphadenectomy. Functioning tumors should be resected regardless the dimension of the lesion. Locally advanced and metastatic disease should be also treated with extended resections, keeping in consideration the grading, size, Ki67, and presence of extra-abdominal disease. In the case of metastases the panel of operative treatment includes resection, ablation, up to liver transplantation.

7 Article Management of small asymptomatic nonfunctioning pancreatic neuroendocrine tumors: Limitations to apply guidelines into real life. 2019

Partelli, Stefano / Mazza, Michele / Andreasi, Valentina / Muffatti, Francesca / Crippa, Stefano / Tamburrino, Domenico / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; Vita e Salute University, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. · Vita e Salute University, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; Vita e Salute University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Surgery · Pubmed #31109657.

ABSTRACT: BACKGROUND: International guidelines suggest a watchful strategy for small nonfunctioning pancreatic neuroendocrine tumors. The aim of this study was to evaluate the management and indications for surgery in patients with asymptomatic nonfunctioning pancreatic neuroendocrine tumors ≤2 cm. METHODS: Patients with asymptomatic, incidental, sporadic nonfunctioning pancreatic neuroendocrine tumors ≤2 cm without nodal or distant metastases were included (2012-2016). A comparison between active surveillance and surgery groups was performed. RESULTS: Of the 101 included patients, 72% underwent active surveillanc and 28% were surgically treated. Patients submitted to surgery were significantly younger (53 vs 60 years, P = .013), had a higher incidence of positive CONCLUSION: One-third of patients with asymptomatic small nonfunctioning pancreatic neuroendocrine tumors ≤2 cm underwent surgery. Patient's preference, initial tumor size, and young age were the main determinants of surgical indication. Preoperative diagnostic workup, including

8 Article Risk and Predictors of Postoperative Morbidity and Mortality After Pancreaticoduodenectomy for Pancreatic Neuroendocrine Neoplasms: A Comparative Study With Pancreatic Ductal Adenocarcinoma. 2019

Partelli, Stefano / Tamburrino, Domenico / Cherif, Rim / Muffatti, Francesca / Moggia, Elisabetta / Gaujoux, Sébastien / Sauvanet, Alain / Falconi, Massimo / Fusai, Giuseppe. ·Department of HPB and Liver Transplant Surgery, Royal Free Hospital, NHS Foundation Trust, London, United Kingdom. · Chirurgie Hépato-Bilio-Pancréatique, Beaujon Hospital, Paris. ·Pancreas · Pubmed #30946244.

ABSTRACT: OBJECTIVES: Pancreaticoduodenectomy (PD) is associated with a high risk of postoperative complications and mortality. The aim of this study was to compare postoperative morbidity after PD in patients undergoing resections for pancreatic neuroendocrine neoplasms (PanNENs) with patients undergoing the same resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data of 566 patients from 3 European tertiary referral centers between 1998 and 2014 were considered. RESULTS: Overall, 566 patients (179 with PanNENs, 387 with PDAC) who underwent PD were analyzed. Patients with PanNENs were significantly younger (56 vs 64 years, P < 0.0001). The consistency of the pancreas was soft in 147 patients (82%) with PanNENs and in 162 patients (42%) with PDAC (P < 0.0001). Patients in the PanNENs group had a significantly higher rate of pancreatic fistula (P < 0.0001), bile leak (P = 0.004), abdominal collection (P = 0.017), and development of sepsis (P = 0.042). No differences in terms of overall postoperative complications, median length of stay, and in-hospital mortality were found. On multivariate analysis sex (male), PanNENs indication, blood transfusion, and a soft pancreatic texture were independent predictors of pancreatic fistula after PD. CONCLUSIONS: Pancreaticoduodenectomy for PanNENs is associated with higher rate of surgical-specific postoperative complications than those for PDAC.

9 Article Ct radiomic features of pancreatic neuroendocrine neoplasms (panNEN) are robust against delineation uncertainty. 2019

Mori, Martina / Benedetti, Giulia / Partelli, Stefano / Sini, Carla / Andreasi, Valentina / Broggi, Sara / Barbera, Maurizio / Cattaneo, Giovanni M / Muffatti, Francesca / Panzeri, Marta / Falconi, Massimo / Fiorino, Claudio / De Cobelli, Francesco. ·Medical Physics, San Raffaele Scientific Institute, Milano, Italy. · Radiology, San Raffaele Scientific Institute, Milano, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute University, Milano, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milano, Italy. · Radiology, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute University, Milano, Italy. · Medical Physics, San Raffaele Scientific Institute, Milano, Italy. Electronic address: fiorino.claudio@hsr.it. ·Phys Med · Pubmed #30738530.

ABSTRACT: PURPOSE: The aim of this study was to quantify the impact of CT delineation uncertainty of pancreatic neuroendocrine neoplasms (panNEN) on Radiomic features (RF). METHODS: Thirty-one previously operated patients were considered. Three expert radiologists contoured panNEN lesions on pre-surgical high-resolution contrast-enhanced CT images and contours were transferred onto pre-contrast CT. Volume agreement was quantified by the DICE index. After images resampling and re-binning, 69 RF were extracted and the impact of inter-observer variability was assessed by Intra-Class Correlation (ICC): ICC > 0.80 was considered as a threshold for "very high" inter-observer agreement. RESULTS: The median volume was 1.3 cc (range: 0.2-110 cc); a satisfactory inter-observer volume agreement was found (mean DICE = 0.78). Only 4 RF showed ICC < 0.80 (0.48-0.73), including asphericity and three RFs (of five) of the neighborhood intensity difference matrix (NID). CONCLUSIONS: The impact of inter-observer variability in delineating panNEN on RF was minimum, with the exception of the NID family and asphericity, showing a moderate agreement. These results support the feasibility of studies aiming to assess CT radiomic biomarkers for panNEN.

10 Article The size of well differentiated pancreatic neuroendocrine tumors correlates with Ki67 proliferative index and is not associated with age. 2019

Partelli, Stefano / Muffatti, Francesca / Rancoita, Paola Maria Vittoria / Andreasi, Valentina / Balzano, Gianpaolo / Crippa, Stefano / Doglioni, Claudio / Rubini, Corrado / Zamboni, Giuseppe / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · University Centre for Statistics in the Biomedical Sciences, "Vita-Salute" University, Milan, Italy. · Department of Pathology, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Pathology, Polytechnic University of Marche Region, Ancona, Italy. · Department of Pathology, "Sacro Cuore-Don Calabria" Hospital, Negrar, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Dig Liver Dis · Pubmed #30723019.

ABSTRACT: BACKGROUND: Concerns exist about a conservative management of well-differentiated nonfunctioning small pancreatic neuroendocrine tumors (NF-PanNET) in young patients and when preoperative Ki67 proliferative index is ≥3%. AIM: To evaluate an association between age, tumor size and grading in patients with sporadic NF-PanNET who underwent curative resection. METHODS: Patients who underwent surgery for sporadic NF-PanNET (excluding G3) were retrospectively analyzed. Linear regression analysis was performed to evaluate a possible correlation between continuous variables, whereas multiple logistic regression analysis was performed for determining predictors of NF-PanNET-G2. RESULTS: Overall, 235 patients with NF-PanNET-G1/G2 were included. The median largest radiological diameter was 25 mm. Age correlated neither with tumor size (P = 0.675) nor with Ki67 index (P = 0.376). On multivariate linear regression analysis, factors independently associated with Ki67 index were NF-PanNET size (P = 0.031), perineural invasion (P = 0.004), microvascular invasion (P = 0.001) and necrosis (P = 0.009). The most accurate NF-PanNET size for predicting NF-PanNET-G2 was 25 mm. On multivariate analysis, a NF-PanNET size >25 mm was independently associated with the risk of having a PanNET-G2 (P = 0.025). CONCLUSION: No correlations exist between age and NF-PanNET size or proliferative index. Therefore, an a priori aggressive attitude is not justified in young patients with small NF-PanNET, as a long-life expectancy is probably unlikely to increase the risk of malignant transformation.

11 Article Association between preoperative Vasostatin-1 and pathological features of aggressiveness in localized nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET). 2019

Andreasi, Valentina / Partelli, Stefano / Manzoni, Marco / Muffatti, Francesca / Colombo, Barbara / Corti, Angelo / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; "Vita e Salute" University, Milan, Italy. · Endocrinology Unit, San Raffaele Scientific Institute, Milan, Italy. · Experimental Oncology Division, San Raffaele Scientific Institute, Milan, Italy. · Experimental Oncology Division, San Raffaele Scientific Institute, Milan, Italy; "Vita e Salute" University, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; "Vita e Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Pancreatology · Pubmed #30470614.

ABSTRACT: BACKGROUND: A reliable and accessible biomarker for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNET) is currently unavailable. Chromogranin A (CgA) represents the best-described neuroendocrine biomarker, but its accuracy is low. Vasostatin-1 (VS-1), a fragment derived from the cleavage of CgA, was recently investigated and found to be more accurate as tumor biomarker in a cohort of patients affected by mainly metastatic small intestinal NET. METHODS: Patients submitted to surgery for sporadic localized NF-PanNET at San Raffaele Hospital were included. Preoperative plasma samples were prospectively collected. Circulating levels of total-CgA and VS-1 were retrospectively investigated by sandwich Enzyme-Linked ImmunoSorbent Assays. RESULTS: Overall, 50 patients were included. VS-1 value (P=0.0001) was the only preoperatively retrievable factor independently associated with NF-PanNET size. No significant correlation between CgA and tumor diameter was found (P = 0.057). A VS-1 value of 0.39 nM was identified as the optimal VS-1 cut-off accurately associated with NF-PanNET larger than 4 cm. Patients with VS-1 > 0.39 nM had a significantly higher frequency of microvascular invasion (P = 0.005) and nodal metastasis (P = 0.027). Median VS-1 plasma level was significantly higher in the presence of microvascular invasion (P = 0.001) and nodal metastasis (P = 0.012). PPI assumption significantly increased total-CgA levels, but not those of VS-1 (P = 0.111). CONCLUSIONS: In localized, non-metastatic NF-PanNET, VS-1 is strongly associated to tumor dimension and its plasma levels are significantly higher in the presence of microvascular invasion and nodal metastases; moreover, VS-1 value is not affected by the PPI use.

12 Article Recurrence of Pancreatic Neuroendocrine Tumors and Survival Predicted by Ki67. 2018

Genç, C G / Falconi, M / Partelli, S / Muffatti, F / van Eeden, S / Doglioni, C / Klümpen, H J / van Eijck, C H J / Nieveen van Dijkum, E J M. ·Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. · Pancreatic Surgery Unit, Pancreas Translational and Research Institute, Scientific Institute, San Raffaele Hospital, University Vita e Salute, Milan, Italy. · Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands. · Department of Pathology, Scientific Institute, San Raffaele Hospital, University Vita e Salute, Milan, Italy. · Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands. · Cancer Center Amsterdam, Amsterdam, The Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands. e.j.nieveenvandijkum@amc.uva.nl. ·Ann Surg Oncol · Pubmed #29789972.

ABSTRACT: BACKGROUND: Despite evidence of different malignant potentials, postoperative follow-up assessment is similar for G1 and G2 pancreatic neuroendocrine tumors (panNETs) and adjuvant treatment currently is not indicated. This study investigated the role of Ki67 with regard to recurrence and survival after curative resection of panNET. METHODS: Patients with resected non-functioning panNET diagnosed between 1992 and 2016 from three institutions were retrospectively analyzed. Patients who had G1 or G2 tumor without distant metastases or hereditary syndromes were included in the study. The patients were re-categorized into Ki67 0-5 and Ki67 6-20%. Cox regression analysis with log-rank testing for recurrence and survival was performed. RESULTS: The study enrolled 241 patients (86%) with Ki67 0-5% and 39 patients (14%) with Ki67 6-20%. Recurrence was seen in 34 patients (14%) with Ki67 0-5% after a median period of 34 months and in 16 patients (41%) with Ki67 6-20% after a median period of 16 months (p < 0.001). The 5-year recurrence-free and 10-year disease-specific survival periods were respectively 90 and 91% for Ki67 0-5% and respectively 55 and 26% for Ki67 6-20% (p < 0.001). The overall survival period after recurrence was 44.9 months, which was comparable between the two groups (p = 0.283). In addition to a Ki67 rate higher than 5%, tumor larger than 4 cm and lymph node metastases were independently associated with recurrence. CONCLUSIONS: Patients at high risk for recurrence after curative resection of G1 or G2 panNET can be identified by a Ki67 rate higher than 5%. These patients should be more closely monitored postoperatively to detect recurrence early and might benefit from adjuvant treatment. A clear postoperative follow-up regimen is proposed.

13 Article The number of positive nodes accurately predicts recurrence after pancreaticoduodenectomy for nonfunctioning neuroendocrine neoplasms. 2018

Partelli, Stefano / Javed, Ammar A / Andreasi, Valentina / He, Jin / Muffatti, Francesca / Weiss, Matthew J / Sessa, Fausto / La Rosa, Stefano / Doglioni, Claudio / Zamboni, Giuseppe / Wolfgang, Christopher L / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Medicine and Surgery, University of Insubria, Varese, Italy. · Service of Clinical Pathology, Lausanne University Hospital, Institute of Pathology, Lausanne, Switzerland. · Department of Pathology, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Pathology, Ospedale "Sacro Cuore-Don Calabria", Negrar, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #29610023.

ABSTRACT: BACKGROUND: The most appropriate nodal staging for pancreatic neuroendocrine neoplasms (PanNENs) is unclear. Aim of the study was to evaluate the effect of the number of positive lymph nodes on prognosis after pancreaticoduodenectomy for PanNENs. METHODS: A retrospective analysis of pancreaticoduodenectomies for nonfunctioning PanNENs was performed. PanNENs with nodal metastases (N+) were classified into N1 (1 to 3 positive lymph nodes) and N2 (4 or more positive lymph nodes). Univariate and multivariate analyses of disease-free survival were performed. RESULTS: 157 patients were included. 99 patients (63%) had N0 PanNENs whereas 58 patients (37%) had nodal involvement (N+). Patients with N0 PanNENs had a 3-year disease-free survival rate of 89% compared with 83% and 75% in patients with N1 and N2 PanNENs, respectively (P < 0.0001). Independent predictors of disease-free survival were the presence of necrosis, lymph node ratio and nodal status. Factors positively correlated with the number of positive lymph nodes were the Ki67 value, the T stage and the number of examined lymph nodes. Similar percentage of N0 and N+ PanNENs was demonstrated for a cut-off of 13 examined lymph nodes. CONCLUSIONS: The number of positive lymph nodes is accurate in predicting recurrence for PanNENs. Thirteen examined lymph nodes seems to be the minimum number of lymph nodes to be resected/examined in patients who undergo pancreaticoduodenectomy for PanNENs.

14 Article Peptide receptor radionuclide therapy as neoadjuvant therapy for resectable or potentially resectable pancreatic neuroendocrine neoplasms. 2018

Partelli, Stefano / Bertani, Emilio / Bartolomei, Mirco / Perali, Carolina / Muffatti, Francesca / Grana, Chiara Maria / Schiavo Lena, Marco / Doglioni, Claudio / Crippa, Stefano / Fazio, Nicola / Zamboni, Giuseppe / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Surgery Department, European Institute of Oncology, Milan, Italy. · Nuclear Medicine Department, "S. Anna" Hospital, Ferrara, Italy. · Nuclear Medicine Department, European Institute of Oncology, Milan, Italy. · Pathology Department, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Oncology Department, European Institute of Oncology, Milan, Italy. · Pathology Department, "Sacro Cuore-Don Calabria" Hospital, Negrar, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Surgery · Pubmed #29284590.

ABSTRACT: BACKGROUND: Peptide receptor radionuclide therapy is a valid therapeutic option for pancreatic neuroendocrine neoplasms. The aim of this study was to describe an initial experience with the use of peptide receptor radionuclide therapy as a neoadjuvant agent for resectable or potentially resectable pancreatic neuroendocrine neoplasms. METHODS: The postoperative outcomes of 23 patients with resectable or potentially resectable pancreatic neuroendocrine neoplasms at high risk of recurrence who underwent neoadjuvant peptide receptor radionuclide therapy (peptide receptor radionuclide therapy group) were compared with 23 patients who underwent upfront surgical operation (upfront surgery group). Patients were matched for tumor size, grade, and stage. Median follow-up was 61 months. RESULTS: The size (median greatest width) of the primary pancreatic neuroendocrine neoplasms decreased after neoadjuvant peptide receptor radionuclide therapy (59 to 50 mm; P=.047). There were no differences in intraoperative and postoperative outcomes and there were no operative deaths, but the risk of developing a pancreatic fistula tended to be less in the peptide receptor radionuclide therapy group when compared to the upfront surgery group (0/23 vs 4/23; P < .02). The incidence of nodal metastases at the time of resection was also less in the peptide receptor radionuclide therapy group (n= 9/23 vs 17/23; P<.02). Neither median disease-specific survival (not reached in either group; P=.411) nor progression-free survival (52 vs 37 months; P>.2) differed between groups, but progression-free survival in the 31 patients who had an R0 resection seemed to be greater in the 15 patients in the peptide receptor radionuclide therapy group versus 16 patients the upfront group (median progression-free survival not reached vs 36 months; P<.05). CONCLUSION: Neoadjuvant peptide receptor radionuclide therapy for resectable or potentially resectable pancreatic neuroendocrine neoplasms in patients with high-risk features of recurrence seems to be beneficial, but well-designed and much larger prospective trials are needed to confirm the safety and the oncologic value of this approach.

15 Article A Systematic review and meta-analysis on the role of palliative primary resection for pancreatic neuroendocrine neoplasm with liver metastases. 2018

Partelli, Stefano / Cirocchi, Roberto / Rancoita, Paola M V / Muffatti, Francesca / Andreasi, Valentina / Crippa, Stefano / Tamburrino, Domenico / Falconi, Massimo. ·Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. · Department of Digestive and Liver Surgery Unit, St Maria Hospital, Terni, Italy. · University Centre for Statistics in the Biomedical Sciences, "Vita-Salute" University, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy; Digestive Oncology PhD Program, La Sapienza University, Rome, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·HPB (Oxford) · Pubmed #29196022.

ABSTRACT: BACKGROUND: Role of palliative pancreatic neuroendocrine neoplasm (PanNEN) resection (pPanNEN-R) is controversial. This study was designed as a meta-analysis of studies which allow a comparison of pPanNEN-R and non-surgical management (PanNEN-nR). METHODS: All published studies until 2017 allowing for the comparison of pPanNEN-R and PanNEN-nR were reviewed. Primary outcome was overall survival (OS). Secondary outcomes measures included postoperative morbidity, reoperation, readmission, length of hospital stay (LOS), and quality of life (QoL). Risk of death was compared by computing the odds-ratio (OR), while 5- and 10-year OS using weighted mean differences. RESULTS: Seven studies were included. A total of 885 patients were included, of whom 252 (28%) underwent pPanNEN-R and 633 (72%) underwent PanNEN-nR. Overall quality of included studies was fair. The risk of death was significantly reduced in patients who underwent pPanNEN-R compared to those who underwent PanNEN-nR (OR = 0.38, 95% CI 0.23-0.65). Data on postoperative morbidity, reoperation, readmission, LOS, and QoL were not adequately reported therefore a meta-analysis for the secondary outcomes was not performed. DISCUSSION: pPanNEN-R in patients with unresectable LM seems to be associated with a better OS compared to non-surgical management but the limitations of included studies does not allow firm conclusions.

16 Article Clinical Usefulness of 2018

Rinzivillo, Maria / Partelli, Stefano / Prosperi, Daniela / Capurso, Gabriele / Pizzichini, Patrizia / Iannicelli, Elsa / Merola, Elettra / Muffatti, Francesca / Scopinaro, Francesco / Schillaci, Orazio / Salgarello, Matteo / Falconi, Massimo / Delle Fave, Gianfranco / Panzuto, Francesco. ·Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy. · Division of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Vita e Salute University, Milan, Italy. · Department of Nuclear Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. · Department of Radiology, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy. · Department of Nuclear Medicine, University of Tor Vergata, Rome, Italy. · Department of Nuclear Medicine, Ospedale Sacro Cuore Don Calabria, Negrar, Italy. · Digestive and Liver Disease Unit, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy fpanzuto@ospedalesantandrea.it. ·Oncologist · Pubmed #29118267.

ABSTRACT: BACKGROUND: The role of RESULTS: A total of 93 patients, including 69 patients with pancreatic NENs and 24 patients with small-intestine NENs, were included. At the time of study entry, 64 patients (68.8%) had PD, and the remaining 29 patients (31.2%) had SD. A total of 62 patients (66.7%) had positive IMPLICATIONS FOR PRACTICE: The findings of the present study may help physicians dealing with advanced neuroendocrine neoplasms to select patients for whom

17 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.

18 Article A New Scoring System to Predict Recurrent Disease in Grade 1 and 2 Nonfunctional Pancreatic Neuroendocrine Tumors. 2018

Genç, Cansu G / Jilesen, Anneke P / Partelli, Stefano / Falconi, Massimo / Muffatti, Francesca / van Kemenade, Folkert J / van Eeden, Susanne / Verheij, Joanne / van Dieren, Susan / van Eijck, Casper H J / Nieveen van Dijkum, Elisabeth J M. ·Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands. · Pancreatic Surgery Unit, Pancreas Translational & Research Institute, Scientific Institute San Raffaelle Hospital & University Vita e Salute, Milano, Italy. · Department of Pathology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Methodology and Statistic CRU, Academic Medical Center, Amsterdam, the Netherlands. · Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands. ·Ann Surg · Pubmed #28594340.

ABSTRACT: OBJECTIVE: The aim of this study was to predict recurrence in patients with grade 1 or 2 nonfunctioning pancreatic neuroendocrine tumors (NF-pNET) after curative resection. BACKGROUND: Surgical resection is the preferred treatment for NF-pNET; however, recurrence occurs frequently after curative surgery, worsening prognosis of patients. METHODS: Retrospectively, patients with NF-pNET of 3 institutions were included. Patients with distant metastases, hereditary syndromes, or grade 3 tumors were excluded. Local or distant tumor recurrence was scored. Independent predictors for survival and recurrence were identified using Cox-regression analysis. The recurrence score was developed to predict recurrence within 5 years after curative resection of grade 1 to 2 NF-pNET. RESULTS: With a median follow-up of 51 months, 211 patients with grade 1 to 2 NF-pNET were included. Thirty-five patients (17%) developed recurrence. The 5- and 10-year disease-specific/overall survival was 98%/91% and 84%/68%, respectively. Predictors for recurrence were tumor grade 2, lymph node metastasis, and perineural invasion. On the basis of these predictors, the recurrence score was made. Discrimination [c-statistic 0.81, 95% confidence interval (95% CI) 0.75-0.87] and calibration (Hosmer Lemeshow Chi-square 11.25, P = 0.258) indicated that the ability of the recurrence score to identify patients at risk for recurrence is good. CONCLUSIONS: This new scoring system could predict recurrence after curative resection of grade 1 and 2 NF-pNET. With the use of the recurrence score, less extensive follow-up could be proposed for patients with low recurrence risk. For high-risk patients, clinical trials should be initiated to investigate whether adjuvant therapy might be beneficial. External validation is ongoing due to limited availability of adequate cohorts.

19 Article Is there a role for surgical resection in patients with pancreatic cancer with liver metastases responding to chemotherapy? 2016

Crippa, S / Bittoni, A / Sebastiani, E / Partelli, S / Zanon, S / Lanese, A / Andrikou, K / Muffatti, F / Balzano, G / Reni, M / Cascinu, S / Falconi, M. ·Department of Surgery, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Department of Oncology, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy. · Department of Surgery, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy. · Department of Oncology, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. · Department of Surgery, IRCCS Ospedale San Raffaele, Vita-Salute University, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #27423449.

ABSTRACT: BACKGROUND: New chemotherapeutic regimens have improved survival for stage IV pancreatic ductal adenocarcinoma and occasionally major response of liver metastases can be observed. Aim of this work is to analyze the outcomes of patients undergoing primary chemotherapy for liver metastases from pancreatic cancer and to evaluate the results of surgical resection. METHODS: Retrospective analysis. EXCLUSION CRITERIA: patients with extra-hepatic metastases, patients with Eastern Cooperative Oncology Group performance status ≥3, patients undergoing supportive care alone. RESULTS: 127 patients were identified. Liver metastases were unilobar in 28.5% of patients. Chemotherapy regimens included gemcitabine alone or in association with other agents (44%), oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX 8%), and cisplatin, gemcitabine plus capecitabine and epirubicin (PEXG) or capecitabine and docetaxel (PDXG) or epirubicin and fluorouracil (PEFG) (48%). 56 patients (44%) had a complete (7%) or partial response (37%). surgical resection was carried out in 11 patients (8.5%). Median overall survival was 11 months for the entire cohort and 15 months for those with partial/complete response. In this sub-group median survival was significantly longer (46 versus 11 months) for patients undergoing resection (P < 0.0001). Independent predictors of overall survival were chemotherapy with multiple agents (HR: 0.512), surgical resection (HR: 0.360), >5 liver metastases at diagnosis (HR: 3.515), and CA 19.9 reduction < 50% of baseline value (HR: 2.708). CONCLUSIONS: Surgical resection of primary pancreatic tumor with or without residual liver disease can be considered in selected cases after primary chemotherapy and it is associated with improved survival.