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Pancreatic Neoplasms: HELP
Articles by Letizia Boninsegna
Based on 24 articles published since 2010
(Why 24 articles?)

Between 2010 and 2020, L. Boninsegna wrote the following 24 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Review Role of resection of the primary pancreatic neuroendocrine tumour only in patients with unresectable metastatic liver disease: a systematic review. 2011

Capurso, Gabriele / Bettini, Rossella / Rinzivillo, Maria / Boninsegna, Letizia / Delle Fave, Gianfranco / Falconi, Massimo. ·Digestive and Liver Disease Unit, II School of Medicine, 'Sapienza' University of Rome, Rome, Italy. ·Neuroendocrinology · Pubmed #21358176.

ABSTRACT: BACKGROUND: Surgery remains the only curative option for pancreatic neuroendocrine tumours (PNETs), but its indication is limited by metastatic disease in most patients. Indication for removing the primary lesion only in the setting of unresectable liver disease is controversial. The present systematic review aims at determining the potential bene- fits (survival, progression-free survival) or harms (morbidity, mortality) of surgical resection of the primary lesion only in patients with PNETs and unresectable metastases. METHODS: Medline was queried for studies reporting the outcome of PNET patients with unresectable liver metastases whenever there was an explicit comparison between resection of the primary lesion only ('active treatment') and no resection ('non-active treatment'). The primary outcome was survival; possible secondary outcomes were progression-free survival, treatment-related mortality and morbidity, and relief of symptoms. RESULTS: Only 3 cohort studies found were eligible and analysed; no meta-analysis could be performed. The number of patients undergoing 'active treatment' varied from 16 to 20, with a percentage ranging from 17 to 39% of cohorts. Survival was longer in patients who received 'active treatment' in 2 studies, and the 5-year survival rate also seemed higher, without significant complications. DISCUSSION: Available data suggest a possible benefit of resection of the primary lesion only in this setting. However, a bias towards a more aggressive surgical approach in patients with a better performance status or less advanced disease seems likely, and no conclusion can be drawn except for the need of randomised trials. We calculated that such a trial would require at least 118 patients per arm.

2 Review Imaging of neuroendocrine gastroenteropancreatic tumours. 2010

Graziani, R / Brandalise, A / Bellotti, M / Manfredi, R / Contro, A / Falconi, M / Boninsegna, L / Pozzi Mucelli, R. ·Dipartimento di Scienze Morfologico-Biomediche, Policlinico G.B. Rossi, Istituto di Radiologia, Verona, Italy. graziani.rossella@azosp.univr.it ·Radiol Med · Pubmed #20221711.

ABSTRACT: The role of imaging in functioning endocrine tumours (FETs) is primarily to detect the tumour, that is, to verify lesion number and location. Radiological detection of carcinoid tumours is limited by typical tumour location throughout the gastrointestinal tract or appendix and is therefore dependent on the tumour being large enough to make it recognisable in that site. The most common FET is insulinoma, which is commonly characterised by the typical appearance of a hypervascular lesion at multidetector-row computed tomography and magnetic resonance imaging. A particularly important role is played by intraoperative ultrasound in defining the exact number of lesions, their relationship with adjacent vascular structures and the pancreatic duct for the purposes of correct surgical planning (enucleation or resection). In the setting of nonfunctioning endocrine tumours (NFETs), which manifest late as large masses causing compression symptoms or as incidental findings, imaging is not primarily aimed at tumour detection, as this is relatively easy given the large size of the lesions. Rather, its role is to characterise the tumour and, in particular, to differentiate pancreatic NFET from ductal adenocarcinoma, as in comparison, malignant NFETs have a more favourable prognosis (5-year survival rate 40% compared with 3%-5% for adenocarcinoma) and therefore require different treatment approaches. As NFET are often malignant, they also require accurate staging and appropriate follow-up. In 80% of cases, NFETs have a "typical" imaging appearance: location in the pancreatic head, large dimensions (diameter between 5 and 15 cm, >10 cm in 30% of cases), capsule, sharp and regular margins owing to the expansile and noninfiltrative growth pattern, solid density and arterial hypervascularity. Some 20% of NFETs display different imaging characteristics ("atypical" appearance) as a result of arterial hypovascularity due to the presence of abundant fibrous stroma. Lastly, a small percentage of NFETs has yet a different appearance ("unusual") due to the cystic nature and/or diffuse location throughout the pancreatic parenchyma.

3 Clinical Trial Clinicopathological features of pancreatic endocrine tumors: a prospective multicenter study in Italy of 297 sporadic cases. 2010

Zerbi, Alessandro / Falconi, Massimo / Rindi, Guido / Delle Fave, Gianfranco / Tomassetti, Paola / Pasquali, Claudio / Capitanio, Vanessa / Boninsegna, Letizia / Di Carlo, Valerio / Anonymous6020648. ·Department of Surgery, Pancreas Unit, San Raffaele Scientific Institute, Milan, Italy. zerbi.alessandro@hsr.it ·Am J Gastroenterol · Pubmed #20087335.

ABSTRACT: OBJECTIVES: Information on pancreatic endocrine tumors (PETs) comes mostly from small, retrospective, uncontrolled studies conducted on highly selected patients. The aim of the study was to describe the clinical and pathological features of PETs in a prospective, multicenter study. METHODS: Newly diagnosed, histologically proven, sporadic PETs observed from June 2004 to March 2007 in 24 Italian centers were included in a specific data set. RESULTS: Two hundred ninety-seven patients (mean age 58.6+/-14.7 years, females 51.2%, males 48.8%) were analyzed. In 73 cases (24.6%), the tumor was functioning (F) (53 insulinomas, 15 gastrinomas, 5 other syndromes) and in 232 (75.4%) it was non-functioning (NF); in 115 cases (38.7%), the diagnosis was incidental. The median tumor size was 20 mm (range 2-150). NF-PETs were significantly more represented among carcinomas (P<0.001). Nodal and liver metastases were detected in 84 (28.3%) and 85 (28.6%) cases, respectively. The presence of liver metastases was significantly higher in the NF-PETs than in the F-PETs (32.1% vs. 17.8%; P<0.05), and in the symptomatic than in the asymptomatic patients (34.6% vs. 19.1%; P<0.005). At the time of recruitment, the majority of patients (251, 84.5%) had undergone surgery, with complete resection in 209 cases (83.3%). CONCLUSIONS: This study points out the high number of new cases of PETs observed in Italy, with a high prevalence of NF and incidentally discovered forms. The size of the tumor was smaller and the rate of metastasis was lower than usually reported, suggesting a trend toward an earlier diagnosis.

4 Article The Evolution of Surgical Strategies for Pancreatic Neuroendocrine Tumors (Pan-NENs): Time-trend and Outcome Analysis From 587 Consecutive Resections at a High-volume Institution. 2019

Landoni, Luca / Marchegiani, Giovanni / Pollini, Tommaso / Cingarlini, Sara / D'Onofrio, Mirko / Capelli, Paola / De Robertis, Riccardo / Davì, Maria V / Amodio, Antonio / Impellizzeri, Harmony / Malpaga, Anna / Miotto, Marco / Boninsegna, Letizia / Crepaz, Lorenzo / Nessi, Chiara / Zingaretti, Caterina C / Paiella, Salvatore / Esposito, Alessandro / Casetti, Luca / Malleo, Giuseppe / Tuveri, Massimiliano / Butturini, Giovanni / Salvia, Roberto / Scarpa, Aldo / Falconi, Massimo / Bassi, Claudio. ·General and Pancreatic Surgery Department, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of Oncology, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of Pathology, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Department of Radiology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy. · Department of Medicine, The Pancreas Institute-University of Verona Hospital Trust, Verona, Italy. · Division of Surgery, Ospedale "Sacro Cuore-Don Calabria", Negrar (VR), Italy. · Department of Surgery, Pederzoli Hospital, Peschiera del Garda, Verona, Italy. · Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy. ·Ann Surg · Pubmed #29189384.

ABSTRACT: OBJECTIVE: The objective of the present analysis is 2-fold: first, to define the evolution of time trends on the surgical approach to pancreatic neuroendocrine neoplasms (Pan-NENs); second, to perform a complete analysis of the predictors of oncologic outcome. BACKGROUND: Reflecting their rarity and heterogeneity, Pan-NENs represent a clinical dilemma. In particular, there is a scarcity of data regarding their long-term follow-up after surgical resection. METHODS: From the Institutional Pan-NEN database, 587 resected cases from 1990 to 2015 were extracted. The time span was arbitrarily divided into 3 discrete clusters enabling a balanced comparison between patient groups. Analyses for predictors of recurrence and survival were performed, together with conditional survival analyses. RESULTS: Among the 587 resected Pan-NENs, 75% were nonfunctioning tumors, and 5% were syndrome-associated tumors. The mean age was 54 years (±14 years), and 51% of the patients were female. The median tumor size was 20 mm (range 4 to 140), 62% were G1, 32% were G2, and 4% were G3 tumors. Time trends analysis revealed that the number of resected Pan-NENs constantly increased, while the size (from 25 to 20 mm) and G1 proportion (from 65% to 49%) decreased during the study period. After a mean follow-up of 75 months, recurrence analysis revealed that nonfunctioning tumors, tumor grade, N1 status, and vascular invasion were all independent predictors of recurrence. Regardless of size, G1 nonfunctioning tumors with no nodal involvement and vascular invasion had a negligible risk of recurrence at 5 years. CONCLUSIONS: Pan-NENs have been increasingly diagnosed and resected during the last 3 decades, revealing reliable predictors of outcome. Functioning and nodal status, tumor grade, and vascular invasion accurately predict survival and recurrence with resulting implications for patient follow-up.

5 Article Are Cystic Pancreatic Neuroendocrine Tumors an Indolent Entity Results from a Single-Center Surgical Series. 2018

Paiella, Salvatore / Marchegiani, Giovanni / Miotto, Marco / Malpaga, Anna / Impellizzeri, Harmony / Montagnini, Greta / Pollini, Tommaso / Nessi, Chiara / Butturini, Giovanni / Capelli, Paola / Posenato, Ilaria / Scarpa, Aldo / D'Onofrio, Mirko / De Robertis, Riccardo / Cingarlini, Sara / Boninsegna, Letizia / Bassi, Claudio / Salvia, Roberto / Landoni, Luca. · ·Neuroendocrinology · Pubmed #28586782.

ABSTRACT: INTRODUCTION: Cystic pancreatic neuroendocrine tumors (CPanNETs) represent an uncommon variant of pancreatic neuroendocrine tumors (PanNETs). Due to their rarity, there is a lack of knowledge with regard to clinical features and postoperative outcome. METHODS: The prospectively maintained surgical database of a high-volume institution was queried, and 46 resected CPanNETs were detected from 1988 to 2015. Clinical, demographic, and pathological features and survival outcomes of CPanNETs were described and matched with a population of 92 solid PanNETs (SPanNETs) for comparison. RESULTS: CPanNETs accounted for 7.8% of the overall number of resected PanNETs (46/587). CPanNETs were mostly sporadic (n = 42, 91%) and nonfunctioning (39%). Two functioning CPanNETs were detected (4.3%), and they were 2 gastrinomas. The median tumor diameter was 30 mm (range 10-120). All tumors were well differentiated, with 38 (82.6%) G1 and 8 (17.4%) G2 tumors. Overall, no CPanNET showed a Ki-67 >5%. A correct preoperative diagnosis of a CPanNET was made in half of the cases. After a median follow-up of >70 months, the 5- and 10-year overall survival of resected CPanNETs was 93.8 and 62.5%, respectively, compared to 92.7 and 84.6% for SPanNETs (p > 0.05). The 5- and 10-year disease-free survival rates were 94.5 and 88.2% for CPanNETs and 81.8 and 78.9% for SPanNETs, respectively (p > 0.05). CONCLUSION: In the setting of a surgical cohort, CPanNETs are rare, nonfunctional, and well-differentiated neoplasms. After surgical resection, they share the excellent outcome of their well-differentiated solid counterparts for both survival and recurrence.

6 Article Pattern and clinical predictors of lymph node involvement in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). 2013

Partelli, Stefano / Gaujoux, Sebastien / Boninsegna, Letizia / Cherif, Rim / Crippa, Stefano / Couvelard, Anne / Scarpa, Aldo / Ruszniewski, Philippe / Sauvanet, Alain / Falconi, Massimo. ·Departments of Surgery and Pathology, University of Verona, Verona, Italy. ·JAMA Surg · Pubmed #23986355.

ABSTRACT: IMPORTANCE: Nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs) are often indolent neoplasms without lymph node (LN) metastasis at diagnosis. Therefore, in patients with low risk of LN metastasis, the extent of surgery and lymphadenectomy could be limited and follow-up adjusted to the very low risk of relapse. OBJECTIVE: To construct a predicting model to assess the risk of pN+ prior to surgical resection for NF-PanNETs using preoperative retrievable variables. DESIGN: Retrospective review using multiple logistic regression analysis to construct predictive model of pN+ based on preoperatively available data. SETTING: The combined prospective databases of the Surgical Departments of the University of Verona, Verona, Italy, and Beaujon Hospital, Clichy, France, were queried for clinical and pathological data. PARTICIPANTS: All patients with resected (R0 or R1), pathologically confirmed NF-PanNETs between January 1, 1993 and December 31, 2009. MAIN OUTCOME AND MEASURE: Risk of lymph node metastases in patients with pancreatic neuroendocrine tumors. RESULTS: Among 181 patients, nodal metastases were reported in 55 patients (30%) and were associated with decreased 5-year disease-free survival (70% vs 97%, P < .001). Multivariable analysis showed that independent factors associated with nodal metastasis were radiological nodal status (rN) (odds ratio [OR], 5.58; P < .001) and tumor grade (NET-G2 vs NET-G1: OR, 4.87; P < .001) (first model). When the tumor grade was excluded, rN (OR, 4.73; P = .001) and radiological tumor size larger than 4 cm (OR, 2.67; P = .03) were independent predictors of nodal metastasis (second model). The area under the receiver operating characteristic curve for the first and second models were 80% and 74%, respectively. CONCLUSIONS AND RELEVANCE: Patients with NF-PanNET-G1 have a very low risk of pN+ in the absence of radiological signs of node involvement. When preoperative grading assessment is not achieved, the radiological size of the lesion is a powerful alternative predictor of pN+. The risk of pathological nodal involvement in patients with NF-PanNETs can be accurately estimated by a clinical predictive model.

7 Article Preoperative assessment of nonfunctioning pancreatic endocrine tumours: role of MDCT and MRI. 2013

Foti, Giovanni / Boninsegna, Letizia / Falconi, Massimo / Mucelli, Roberto Pozzi. ·Dipartimento di Radiologia, Ospedale Sacrocuore Don Calabria, Via don A. Sempreboni 5, 37024, Negrar, Italy, gfoti81@yahoo.it. ·Radiol Med · Pubmed #23801403.

ABSTRACT: PURPOSE: This study was done to compare the diagnostic accuracy of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) in the preoperative assessment of nonfunctioning pancreatic endocrine tumours (NFPET). MATERIALS AND METHODS: Fifty-one patients (25 men, 26 women; mean age, 52 years), preoperatively investigated by both MDCT and MRI and subsequently operated on with a histological diagnosis of NFPET, were included in this study. MDCT and MRI accuracy in evaluating location, size, margins, baseline density/signal intensity, structure, pattern of enhancement, peak enhancement phase, involvement of main pancreatic duct, involvement of adjacent organs, infiltration of peritumoural vessels, involvement of locoregional lymph nodes, and liver metastases was compared using Pearson correlation, Mann-Whitney and chi-square tests. A value of p<0.05 was considered statistically significant. RESULTS: MDCT and MRI had similar accuracy in assessing size, margins, baseline density/signal intensity, structure, pattern of enhancement, peak enhancement phase, involvement of main pancreatic duct, involvement of adjacent organs, involvement of locoregional lymph nodes, and liver metastases (p>0.05). MDCT was superior to MRI in evaluating the infiltration of peritumoural vessels (p=0.025). CONCLUSIONS: MDCT performed better than MRI in assessing vascular involvement and should be considered the best imaging tool for preoperative evaluation of NFPET.

8 Article Presentation, diagnostic features and glucose handling in a monocentric series of insulinomas. 2013

Toaiari, M / Davì, M V / Dalle Carbonare, L / Boninsegna, L / Castellani, C / Falconi, M / Francia, G. ·Department of Internal Medicine D, "G.B. Rossi" University Hospital, Verona, Italy. ·J Endocrinol Invest · Pubmed #23608735.

ABSTRACT: BACKGROUND: New aspects have emerged in the clinical and diagnostic scenarios of insulinoma: current guidelines have lowered the diagnostic insulin threshold to 3 μU/ml in the presence of hypoglycemia (<55 mg/dl); post-prandial hypoglycemia has been reported as the only presenting symptom; preexisting diabetes mellitus (DM) was recognized in some patients. AIM: To evaluate clinical features, diagnostic criteria and glucose metabolic profile in a monocentric series of patients affected by insulinomas including two subgroups: sporadic and multiple endocrine neoplasia type-1 syndrome (MEN-1). SUBJECTS AND METHODS: Clinical, pathological and biochemical data regarding 33 patients were analyzed. RESULTS: following the current guidelines the 72-h fasting test was initially positive in all cases but one. In this case the test, initially negative, became positive after a 2-yr follow-up. Nadir insulin level was ≥ 3 μU/ml but <6 μU/ml in 3 patients and ≥ 6 μU/ml in the remaining 30 cases. At presentation, 27 patients (82%) reported only fasting symptoms, 3 (9%) only post-prandial and 3 (9%) both. Seven cases (21%) had previously been affected by type 2 DM or impaired glucose metabolism. CONCLUSIONS: In our series the new cut-off of insulin increased the sensitivity of the 72-h fasting test from 87% to 97%. The absence of hypoglycemia during the test cannot definitively rule out the diagnosis and the test should be repeated in every highly suspicious case. Post-prandial hypoglycemia can be the only presenting symptom. DM may be associated with the occurrence of insulinoma. So that a possible diagnosis of insulinoma must not be ignored if previous impaired glucose handling is evident.

9 Article Treatment of malignant pancreatic neuroendocrine neoplasms: middle-term (2-year) outcomes of a prospective observational multicentre study. 2013

Zerbi, Alessandro / Capitanio, Vanessa / Boninsegna, Letizia / Delle Fave, Gianfranco / Pasquali, Claudio / Rindi, Guido / Campana, Davide / Falconi, Massimo / Anonymous1830752. ·Pancreatic Surgery, Department of Surgery, Humanitas Clinical and Research Center, Milan, Italy. ·HPB (Oxford) · Pubmed #23472667.

ABSTRACT: BACKGROUND: Information on malignant pancreatic neuroendocrine neoplasms (pNENs) is mostly from retrospective studies in highly selected patients. The aim of this prospective, multicentre study was to assess treatment and outcomes of malignant pNENs in clinical practice. PATIENTS AND METHODS: Consecutive patients with newly diagnosed, histologically-proven pNENs were included and followed-up for 2 years. Tumours were defined as malignant when nodal or distant metastases were present or invasion of extrapancreatic structures/organs was evident. RESULTS: A total of 140 patients with malignant pNENs were included. Ninety-eight patients (70.0%) underwent a surgical resection (76 radical and 22 palliative). Other non-surgical treatments were used in 101 patients (72.1%): somatostatin analogues (n = 63), chemotherapy (n = 30), ablative treatments (n = 15) and peptide-receptor radionuclide therapy (n = 14). No relationship was observed between the 2010 WHO classification and type of treatment. A surgical resection was more often performed in incidentally detected tumours located in the pancreas body tail. Two-year progression-free survival was 63.8%: 82% after a radical resection, 44% after a palliative resection and 41% without a resection. A radical resection and Ki67 proliferative index >5% and >10% were the only significant prognostic determinants in multivariate analysis. CONCLUSIONS: A radical resection is the cornerstone treatment of malignant pNENs and represents, together with Ki67 assessment, the most powerful prognostic factor for 2-year outcomes.

10 Article Partial pancreaticoduodenectomy can provide cure for duodenal gastrinoma associated with multiple endocrine neoplasia type 1. 2013

Lopez, Caroline L / Falconi, Massimo / Waldmann, Jens / Boninsegna, Letizia / Fendrich, Volker / Goretzki, Peter K / Langer, Peter / Kann, Peter H / Partelli, Stefano / Bartsch, Detlef K. ·Department of Surgery, Philipps-University, Marburg, Germany. ·Ann Surg · Pubmed #22580937.

ABSTRACT: OBJECTIVE: To evaluate the outcome of pancreaticoduodenectomy (PD) versus non-PD resections for the treatment of gastrinoma in multiple endocrine neoplasia type 1. BACKGROUND: Gastrinoma in MEN1 is considered a rarely curable disease and its management is highly controversial both for timing and extent of surgery. METHODS: Clinical characteristics, complications and outcomes of 27 prospectively collected MEN1 patients with biochemically proven gastrinoma, who underwent surgery, were analyzed with special regard to the gastrinoma type and the initial operative procedure. RESULTS: Twenty-two (81%) patients with gastrinoma in MEN1 had duodenal gastrinomas and 5 patients (19%) had pancreatic gastrinomas. At the time of diagnosis, 21 (77%) gastrinomas were malignant (18 duodenal, 3 pancreatic), but distant metastases were only present in 4 (15%) patients. Patients with pancreatic gastrinomas underwent either distal pancreatic resections or gastrinoma enucleation with lymphadenectomy, 2 patients also had synchronous resections of liver metastases. One of these patients was biochemically cured after a median of 136 (77-312) months. Thirteen patients with duodenal gastrinomas underwent PD resections (group 1, partial PD [n = 11], total PD [n = 2]), whereas 9 patients had no-PD resections (group 2) as initial operative procedure. Perioperative morbidity and mortality, including postoperative diabetes, differed not significantly between groups (P > 0.5). All patients of group 1 and 5 of 9 (55%) patients of group 2 had a negative secretin test at hospital discharge. However, after a median follow-up of 136 (3-276) months, 12 (92%) patients of group 1 were still normogastrinemic compared to only 3 of 9 (33%) patients of group 2 (P = 0.023). Three (33%) patients of group 2 had to undergo up to 3 reoperations for recurrent or metastatic disease compared to none of group 1. CONCLUSIONS: Duodenal gastrinoma in MEN1 should be considered a surgically curable disease. PD seems to be the adequate approach to this disease, providing a high cure rate and acceptable morbidity compared to non-PD resections.

11 Article Impact of lymphadenectomy on survival after surgery for sporadic gastrinoma. 2012

Bartsch, D K / Waldmann, J / Fendrich, V / Boninsegna, L / Lopez, C L / Partelli, S / Falconi, M. ·Department of Surgery, University Hospital Giessen and Marburg, Marburg, Germany. ·Br J Surg · Pubmed #22864882.

ABSTRACT: BACKGROUND: The study was undertaken to determine prognostic factors and the value of systematic lymphadenectomy on survival in sporadic gastrinoma. METHODS: Patients with sporadic gastrinoma who underwent initial surgery during a 21-year period in two tertiary referral centres were analysed retrospectively with respect to clinical characteristics, operative procedures and outcome. RESULTS: Forty-eight patients with a median age of 52 (range 22-73) years were analysed. Some 18 patients had pancreatic and 26 had duodenal gastrinomas, whereas the primary tumour remained unidentified in four patients. After a median postoperative follow-up of 83 (range 3-296) months, 20 patients had no evidence of disease, 13 patients were alive with disease, 11 patients had died from the disease and four had died from unrelated causes. In 41 patients who underwent potentially curative surgery, systematic lymphadenectomy with excision of more than ten lymph nodes resulted in a higher rate of biochemical cure after surgery than no or selective lymphadenectomy (13 of 13 versus 18 of 28 patients; P = 0·017), with a trend towards prolonged disease specific survival (P = 0·062) and disease-free survival (P = 0·120), and a reduced risk of death (0 of 13 versus 7 of 24 patients; P = 0·037). Negative prognostic factors for disease specific survival were pancreatic location (P = 0·029), tumour size equal to or larger than 25 mm (P = 0·003), Ki-67 index more than 5 per cent (P < 0·001), preoperative gastrin level 3000 pg/ml or more (P = 0·003) and liver metastases (P < 0·001). Sex, age, type of surgery and presence of lymph node metastases had no influence on disease free or disease specific survival. CONCLUSION: In sporadic gastrinoma, systematic lymphadenectomy during initial surgery may reduce the risk of persistent disease and improve survival.

12 Article TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. 2012

Rindi, G / Falconi, M / Klersy, C / Albarello, L / Boninsegna, L / Buchler, M W / Capella, C / Caplin, M / Couvelard, A / Doglioni, C / Delle Fave, G / Fischer, L / Fusai, G / de Herder, W W / Jann, H / Komminoth, P / de Krijger, R R / La Rosa, S / Luong, T V / Pape, U / Perren, A / Ruszniewski, P / Scarpa, A / Schmitt, A / Solcia, E / Wiedenmann, B. ·Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore, Histopathology and Cytodiagnosis Unit, Policlinico Gemelli, Largo A. Gemelli, 8, Roma I-00168, Italy. guido.rindi@rm.unicatt.it ·J Natl Cancer Inst · Pubmed #22525418.

ABSTRACT: BACKGROUND: Both the European Neuroendocrine Tumor Society (ENETS) and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization (UICC/AJCC/WHO) have proposed TNM staging systems for pancreatic neuroendocrine neoplasms. This study aims to identify the most accurate and useful TNM system for pancreatic neuroendocrine neoplasms. METHODS: The study included 1072 patients who had undergone previous surgery for their cancer and for which at least 2 years of follow-up from 1990 to 2007 was available. Data on 28 variables were collected, and the performance of the two TNM staging systems was compared by Cox regression analysis and multivariable analyses. All statistical tests were two-sided. RESULTS: Differences in distribution of sex and age were observed for the ENETS TNM staging system. At Cox regression analysis, only the ENETS TNM staging system perfectly allocated patients into four statistically significantly different and equally populated risk groups (with stage I as the reference; stage II hazard ratio [HR] of death = 16.23, 95% confidence interval [CI] = 2.14 to 123, P = .007; stage III HR of death = 51.81, 95% CI = 7.11 to 377, P < .001; and stage IV HR of death = 160, 95% CI = 22.30 to 1143, P < .001). However, the UICC/AJCC/WHO 2010 TNM staging system compressed the disease into three differently populated classes, with most patients in stage I, and with the patients being equally distributed into stages II-III (statistically similar) and IV (with stage I as the reference; stage II HR of death = 9.57, 95% CI = 4.62 to 19.88, P < .001; stage III HR of death = 9.32, 95% CI = 3.69 to 23.53, P = .94; and stage IV HR of death = 30.84, 95% CI = 15.62 to 60.87, P < .001). Multivariable modeling indicated curative surgery, TNM staging, and grading were effective predictors of death, and grading was the second most effective independent predictor of survival in the absence of staging information. Though both TNM staging systems were independent predictors of survival, the UICC/AJCC/WHO 2010 TNM stages showed very large 95% confidence intervals for each stage, indicating an inaccurate predictive ability. CONCLUSION: Our data suggest the ENETS TNM staging system is superior to the UICC/AJCC/WHO 2010 TNM staging system and supports its use in clinical practice.

13 Article Surgical management of insulinomas: short- and long-term outcomes after enucleations and pancreatic resections. 2012

Crippa, Stefano / Zerbi, Alessandro / Boninsegna, Letizia / Capitanio, Vanessa / Partelli, Stefano / Balzano, Gianpaolo / Pederzoli, Paolo / Di Carlo, Valerio / Falconi, Massimo. ·Department of Surgery, Chirurgia Generale B, Policlinico GB Rossi, University of Verona, Piazzale La Scuro, 10-37134, Verona, Italy. ·Arch Surg · Pubmed #22430908.

ABSTRACT: OBJECTIVE: To analyze the characteristics and outcomes following enucleation and pancreatic resections of insulinomas. DESIGN: Retrospective cohort study; prospective database. SETTINGS: Academic, tertiary, and referral centers. PATIENTS: Consecutive patients with insulinomas (symptoms of hyperinsulinism and positive fasting glucose test) who underwent surgical treatment between January 1990 and December 2009. MAIN OUTCOME MEASURES: Operative morbidity, tumor recurrence, and survival after treatment. RESULTS: A total of 198 patients (58.5% women; median age, 48 years) were identified. There were 175 (88%) neuroendocrine tumors grade G1 and 23 (12%) neuroendocrine tumors grade G2. Malignant insulinomas defined by lymph node/liver metastases were found in 7 patients (3.5%). Multiple insulinomas were found in 8% of patients, and 5.5% of patients had multiple endocrine neoplasia type 1. Surgical procedures included 106 enucleations (54%) and 92 pancreatic resections (46%). Mortality was nil. Rate of clinically significant pancreatic fistula was 18%. Enucleations had a higher reoperation rate compared with pancreatic resections (8.5% vs 1%; P = .02). Multiple endocrine neoplasia type 1 was significantly associated with younger age at onset (P < .005) and higher rates of malignancies and multiple lesions. Median follow-up was 65 months. Six patients (3%; 5 patients had neuroendocrine tumors grade G2) developed tumor recurrence. Four patients (2%) died of disease. New exocrine (1.5%) and endocrine (4%) insufficiencies were associated only with pancreatic resections. CONCLUSIONS: Outcomes following surgical resection of insulinomas are satisfactory, with no mortality and good functional results. Recurrence is uncommon (3%), and it is more likely associated with neuroendocrine tumors grade G2. Insulinomas in multiple endocrine neoplasia type 1 are at higher risk for being malignant and multifocal, requiring pancreatic resections.

14 Article Malignant pancreatic neuroendocrine tumour: lymph node ratio and Ki67 are predictors of recurrence after curative resections. 2012

Boninsegna, Letizia / Panzuto, Francesco / Partelli, Stefano / Capelli, Paola / Delle Fave, Gianfranco / Bettini, Rossella / Pederzoli, Paolo / Scarpa, Aldo / Falconi, Massimo. ·Department of Surgery, University of Verona, Verona, Italy. ·Eur J Cancer · Pubmed #22129889.

ABSTRACT: INTRODUCTION: Malignant pancreatic neuroendocrine tumours (PNENs) are generally associated with a good prognosis after radical resection. In other pancreatic malignancies predictors of recurrence and the role of lymph node ratio (LNR) are well known, but both have been scarcely investigated for malignant PNETs. METHODS: The prospective database from the surgical Department of Verona University was queried. Clinical and pathological data of all patients with resected malignant PNET between 1990 and 2008 were reviewed. Univariate and multivariate analysis were performed. RESULTS: Fifty-seven patients (male/female ratio=1) with a median age of 58 years (33-78) entered in the study. Twenty-nine (51%) patients underwent pancreaticoduodenectomy and 28 (49%) distal pancreatectomy. Postoperative mortality was nil with a 37% morbidity rate. There were 36 (63%) patients with lymph node metastases (N1). Of these, 23 (64%) had a lymph node ratio (LNR) >0 and ≤0.20 and 13 (36%) had a LNR >0.20. The median overall survival and the median disease free survival (DFS) were 190 and 80 months, respectively. Recurrent disease was identified in 24 patients (42%) with a 2 and 5-year DFS rate of 82% and 49%, respectively. On multivariate analysis, LNR >0.20 (HR=2.75) and a value of Ki67 >5% (HR=3.39) were significant predictors of recurrence (P<0.02). CONCLUSIONS: After resection for malignant PNETs, LNR and a Ki67 >5% are the most powerful predictors of recurrence. The presence of these factors should be considered for addressing patients to adjuvant treatment in future clinical trials.

15 Article Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors. 2011

Malpeli, Giorgio / Amato, Eliana / Dandrea, Mario / Fumagalli, Caterina / Debattisti, Valentina / Boninsegna, Letizia / Pelosi, Giuseppe / Falconi, Massimo / Scarpa, Aldo. ·Department of Pathology and Diagnostics, University of Verona, Verona, Italy. giorgio.malpeli@univr.it ·BMC Cancer · Pubmed #21838870.

ABSTRACT: BACKGROUND: RASSF1A gene silencing by DNA methylation has been suggested as a major event in pancreatic endocrine tumor (PET) but RASSF1A expression has never been studied. The RASSF1 locus contains two CpG islands (A and C) and generates seven transcripts (RASSF1A-RASSF1G) by differential promoter usage and alternative splicing. METHODS: We studied 20 primary PETs, their matched normal pancreas and three PET cell lines for the (i) methylation status of the RASSF1 CpG islands using methylation-specific PCR and pyrosequencing and (ii) expression of RASSF1 isoforms by quantitative RT-PCR in 13 cases. CpG island A methylation was evaluated by methylation-specific PCR (MSP) and by quantitative methylation-specific PCR (qMSP); pyrosequencing was applied to quantify the methylation of 51 CpGs also encompassing those explored by MSP and qMSP approaches. RESULTS: MSP detected methylation in 16/20 (80%) PETs and 13/20 (65%) normal pancreas. At qMSP, 11/20 PETs (55%) and 9/20 (45%) normals were methylated in at least 20% of RASSF1A alleles.Pyrosequencing showed variable distribution and levels of methylation within and among samples, with PETs having average methylation higher than normals in 15/20 (75%) cases (P = 0.01). The evaluation of mRNA expression of RASSF1 variants showed that: i) RASSF1A was always expressed in PET and normal tissues, but it was, on average, expressed 6.8 times less in PET (P = 0.003); ii) RASSF1A methylation inversely correlated with its expression; iii) RASSF1 isoforms were rarely found, except for RASSF1B that was always expressed and RASSF1C whose expression was 11.4 times higher in PET than in normal tissue (P = 0.001). A correlation between RASSF1A expression and gene methylation was found in two of the three PET cell lines, which also showed a significant increase in RASSF1A expression upon demethylating treatment. CONCLUSIONS: RASSF1A gene methylation in PET is higher than normal pancreas in no more than 75% of cases and as such it cannot be considered a marker for this neoplasm. RASSF1A is always expressed in PET and normal pancreas and its levels are inversely correlated with gene methylation. Isoform RASSF1C is overexpressed in PET and the recent demonstration of its involvement in the regulation of the Wnt pathway points to a potential pathogenetic role in tumor development.

16 Article Tumor size correlates with malignancy in nonfunctioning pancreatic endocrine tumor. 2011

Bettini, Rossella / Partelli, Stefano / Boninsegna, Letizia / Capelli, Paola / Crippa, Stefano / Pederzoli, Paolo / Scarpa, Aldo / Falconi, Massimo. ·Department of Surgery, S. Cuore-Don Calabria Hospital, Negrar, Verona, Italy. ·Surgery · Pubmed #21683859.

ABSTRACT: BACKGROUND: Tumor size is a criterion of staging in nonfunctioning pancreatic endocrine tumors as well as a predictor of outcome after curative resection. This study analyzes the correlation between tumor size and malignancy in patients with nonfunctioning pancreatic endocrine tumors. METHODS: All patients with nonfunctioning pancreatic endocrine tumors who underwent curative resection (R0) at our institution between 1990 and 2008 were considered. Their clinicopathologic characteristics were compared among 3 different groups according to tumor size. Univariate and multivariable analyses were performed. RESULTS: Over the study period, 177 patients were identified. Overall, 90 patients (51%) had a tumor size ≤2 cm (group 1), 46 (26%) had tumor size between >2 cm and ≤4 cm (group 2), and 41 (23%) had tumor size >4 cm (group 3). Tumors ≤2 cm were more frequently incidentally discovered (group 1, 57% vs group 2, 51% vs group 3, 32%; P = .014) and benign (group 1, 81% vs group 2, 65% vs group 3, 5%; P < .0001). The presence of a nonfunctioning pancreatic endocrine tumor >2 cm and a nonincidental diagnosis of the tumor were independent predictors of malignancy at multivariable analysis. None of the 51 patients (29%) with a pancreatic endocrine tumor ≤2 cm that was incidentally diagnosed died of disease. CONCLUSION: A strict correlation between tumor size and malignancy in nonfunctioning pancreatic endocrine tumors was demonstrated. A nonoperative management could be advocated for tumors ≤2 cm when discovered incidentally.

17 Article Metastatic and locally advanced pancreatic endocrine carcinomas: analysis of factors associated with disease progression. 2011

Panzuto, Francesco / Boninsegna, Letizia / Fazio, Nicola / Campana, Davide / Pia Brizzi, Maria / Capurso, Gabriele / Scarpa, Aldo / De Braud, Filippo / Dogliotti, Luigi / Tomassetti, Paola / Delle Fave, Gianfranco / Falconi, Massimo. ·II School of Medicine, Sapienza University of Roma, Sant'Andrea Hospital, Via di Grottarossa 1035, Rome, Italy. ·J Clin Oncol · Pubmed #21555696.

ABSTRACT: PURPOSE: Knowledge of clinical course of pancreatic endocrine carcinomas (PECs) is poor. This study aimed to determine the time to progression of advanced PECs, and to identify predictors capable of selecting subgroups with higher risk of progression. PATIENTS AND METHODS: In this multicenter retrospective analysis, patients with advanced PECs were enrolled. Staging was according to European Neuroendocrine Tumors Society guidelines. Grading was based on proliferation index using Ki67 immunohistochemistry. The primary end point was progression-free survival (PFS), which was assessed using the Kaplan-Meier method. The Cox regression proportional hazard model was used to identify predictors for tumor progression. RESULTS: Two hundred two patients with PECs were enrolled, including 172 with well-differentiated and 30 with poorly differentiated endocrine carcinomas. There were 34 patients with stage III and 168 with stage IV tumors. G1 tumors were present in 19.7% of patients, whereas 60.1% of patients had G2 tumors, and the remaining 20.2% had G3 tumors. Disease progression occurred in 166 patients (82.2%), at a median interval of 10 months (interquartile range, 5 to 22) from diagnosis. Median PFS was 14 months. Different PFS were observed depending on G grade (P < .001) and tumor differentiation (P < .001) and in patients who did not receive any antitumor treatment (P = .002). The major risk factor for progression was the proliferation index Ki67 (hazard ratio, 1.02 for each increasing unit; P < .001). Overall 5-year survival was 44.1%. CONCLUSION: The vast majority of patients with advanced PECs undergo disease progression. The major risk factor for progression is Ki67 index, which should lead physicians dealing with PECs to plan appropriate follow-up programs and therapeutic strategies.

18 Article Presentation and outcome of pancreaticoduodenal endocrine tumors in multiple endocrine neoplasia type 1 syndrome. 2011

Davì, Maria Vittoria / Boninsegna, Letizia / Dalle Carbonare, Luca / Toaiari, Marco / Capelli, Paola / Scarpa, Aldo / Francia, Giuseppe / Falconi, Massimo. ·Department of Medicine, University of Verona, Italy. mariavittoria.davi @ ospedaleuniverona.it ·Neuroendocrinology · Pubmed #21464564.

ABSTRACT: AIM: To assess presentation and outcome of pancreaticoduodenal endocrine tumors (PDETs) in a single center series of multiple endocrine neoplasia type 1 (MEN1) patients. METHODS: Retrospective analysis of prospectively collected data of MEN1 patients observed at the University of Verona. RESULTS: Thirty-one MEN1 patients had PDETs, including 16 nonfunctioning (NF), 6 insulinomas and 9 Zollinger-Ellison syndrome (ZES). In 16 of these patients (52%), PDET was the manifestation which led to the diagnosis of MEN1; among this group, 15 patients (94%) previously had unidentified primary hyperparathyroidism (PHPT), which was asymptomatic in 9 cases (60%). Of the 31 patients, 19 (61%) underwent curativesurgery and 13 (68%, 7 NF-PDETs, 4 insulinomas and 2 ZES) were disease-free after a median follow-up of 3 years (range: 0.5-15). One patient had debulking surgery with stable disease after 2 years of follow-up. Eight patients with NF-PDETs ≤20 mm and 2 with ZES, treated with a conservative approach, showed stable disease. One patient with insulinoma was lost to follow-up. CONCLUSIONS: PDET may be the manifestation that leads to MEN1 diagnosis since the almost constant presence of PHPT is very often unrecognized or considered sporadic. Conversely, the presence of PDETs should be looked for in all patients presenting PHPT, even if asymptomatic, particularly before age 50. Surgery may be curative in the majority of insulinomas and can prolong disease-free survival in NF-PDET, but is not proven to be effective in ZES. A conservative approach can be safely reserved for patients with NF-PDETs ≤20 mm.

19 Article Surgical treatment of pancreatic endocrine tumours in Italy: results of a prospective multicentre study of 262 cases. 2011

Zerbi, Alessandro / Capitanio, Vanessa / Boninsegna, Letizia / Pasquali, Claudio / Rindi, Guido / Delle Fave, Gianfranco / Del Chiaro, Marco / Casadei, Riccardo / Falconi, Massimo / Anonymous7250672. ·Pancreatic Surgery Section, Humanitas Scientific Institute, via Manzoni 56, Rozzano, Milan, Italy. alessandro.zerbi@humanitas.it ·Langenbecks Arch Surg · Pubmed #20857140.

ABSTRACT: BACKGROUND: Information on the treatment of pancreatic endocrine tumours (PETs) comes mostly from small, retrospective, uncontrolled studies. METHODS: Newly diagnosed, histologically proven PETs, observed from June 2004 to March 2007 in 24 Italian centres, were included in a specific dataset. RESULTS: Three-hundred and ten patients (mean age 57.6 years, females 46.6%) were analysed. At the time of recruitment, 262 (84.5%) underwent surgery. The percentage of operated patients was 91.9% and 62.0% in surgical and non-surgical centres, respectively. A curative resection was carried out in 83.6% (n = 219) of cases, a palliative resection (debulking) in 10.7% (n = 28), an exploratory laparotomy in 4.6% (n = 12), and a bypass procedure in 1.1% (n = 3). Laparoscopy was performed in 8.0% (n = 21) of cases. Resection consisted of a pancreatoduodenectomy in 46 cases (21.0%), a distal pancreatectomy in 95 (43.4%), an enucleation in 50 (22.8%), a middle pancreatectomy in 16 (7.3%) and a total pancreatectomy in 12 (5.5%). Liver resection was associated with pancreatic resection in 26 cases (9.9%). Post-operative mortality was 1.5% and morbidity 39.7%, respectively. A curative resection was performed more frequently in asymptomatic, small, non-metastatic, benign and at uncertain behaviour tumours, with low Ki67 values. CONCLUSIONS: This study strongly indicates the fact that surgical resection represents the cornerstone treatment of PETs.

20 Article Pancreatic cystic endocrine tumors: a different morphological entity associated with a less aggressive behavior. 2010

Boninsegna, Letizia / Partelli, Stefano / D'Innocenzio, Maria Michela / Capelli, Paola / Scarpa, Aldo / Bassi, Claudio / Pederzoli, Paolo / Falconi, Massimo. ·Department of Surgery, S. Cuore-Don Calabria Hospital, Negrar, Italy. ·Neuroendocrinology · Pubmed #20689265.

ABSTRACT: BACKGROUND: Cystic pancreatic endocrine tumors (CPETs) are rare lesions and their biological features have been scarcely investigated. AIM: To compare clinical and pathological features of resected non-functioning sporadic CPETs (NF-CPETs) with solid pancreatic endocrine tumors (SPETs) in a single-institution experience. METHODS: All patients with a pathologically confirmed diagnosis of sporadic non-functioning pancreatic endocrine tumors who underwent curative resection between 1990 and 2008 were included. A comparison of demographic, clinical and pathological characteristics between CPETs and SPETs was made. Univariate and multivariable analyses were performed to identify preoperative predictors of carcinoma (non-functioning pancreatic endocrine carcinoma). RESULTS: Twenty-one (11.5%) patients with a histological diagnosis of NF-CPET were identified. The median age was 60 years (IQR 46.5-73.5 years) and a diagnosis of carcinoma (non-functioning pancreatic endocrine carcinoma) was made in 3 (14.3%) cases. In the comparison with NF-SPETs, no differences were found in terms of gender (p = 0.75), age (p = 0.81), presenting symptoms (p = 0.43), localization of the tumors (p = 0.46) and type of resection (p = 0.31). The incidence of non-functioning pancreatic endocrine carcinoma was significantly lower in the NF-CPET versus the NF-SPET group (14.3 vs. 40.4%, p = 0.04). By univariate analysis, preoperative predictors of non-functioning pancreatic endocrine carcinoma included the presence of symptoms (OR 3.96, 95% CI 2.06-7.63) and an increase in the absolute value of radiological diameter (OR 1.05, 95% CI 1.03-1.07). A cystic morphology of the lesion turned out to be a negative predictor of carcinoma (OR 0.25, 95% CI 0.70-0.87). These results were confirmed by multivariable analysis. CONCLUSIONS: NF-CPETs have a measurable propensity to be benign. In those patients affected by small and asymptomatic NF-CPET a more conservative surgical approach or a follow-up policy could be considered.

21 Article MEN1 in pancreatic endocrine tumors: analysis of gene and protein status in 169 sporadic neoplasms reveals alterations in the vast majority of cases. 2010

Corbo, Vincenzo / Dalai, Irene / Scardoni, Maria / Barbi, Stefano / Beghelli, Stefania / Bersani, Samantha / Albarello, Luca / Doglioni, Claudio / Schott, Christina / Capelli, Paola / Chilosi, Marco / Boninsegna, Letizia / Becker, Karl-Friedrich / Falconi, Massimo / Scarpa, Aldo. ·ARC-NET Research Center Department of Pathology, University of Verona, Policlinico G.B. Rossi c/o Piastra Odontoiatrica, Piazzale L.A. Scuro 10, Verona, Italy. ·Endocr Relat Cancer · Pubmed #20566584.

ABSTRACT: Pancreatic endocrine tumors (PETs) may be part of hereditary multiple endocrine neoplasia type 1 (MEN1) syndrome. While MEN1 gene mutation is the only ascertained genetic anomaly described in PETs, no data exist on the cellular localization of MEN1-encoded protein, menin, in normal pancreas and PETs. A total of 169 PETs were used to assess the i) MEN1 gene mutational status in 100 clinically sporadic PETs by direct DNA sequencing, ii) immunohistochemical expression of menin in normal pancreas and 140 PETs, including 71 cases screened for gene mutations, and iii) correlation of these findings with clinical-pathological parameters. Twenty-seven PETs showed mutations that were somatic in 25 patients and revealed to be germline in 2 patients. Menin immunostaining showed strong nuclear and very faint cytoplasmic signal in normal islet cells, whereas it displayed abnormal location and expression levels in 80% of tumors. PETs harboring MEN1 truncating mutations lacked nuclear protein, and most PETs with MEN1 missense mutations showed a strong cytoplasmic positivity for menin. Menin was also misplaced in a significant number of cases lacking MEN1 mutations. In conclusion, the vast majority of PETs showed qualitative and/or quantitative alterations in menin localization. In 30% of cases, this was associated with MEN1 mutations affecting sequences involved in nuclear localization or protein-protein interaction. In cases lacking MEN1 mutations, the alteration of one of the menin interactors may have prevented its proper localization, as suggested by recent data showing that menin protein shuttles between the nucleus and cytoplasm and also affects the subcellular localization of its interactors.

22 Article Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. 2010

Scarpa, Aldo / Mantovani, William / Capelli, Paola / Beghelli, Stefania / Boninsegna, Letizia / Bettini, Rossella / Panzuto, Francesco / Pederzoli, Paolo / delle Fave, Gianfranco / Falconi, Massimo. ·Department of Pathology, University of Verona, Verona, Italy. aldo.scarpa@univr.it ·Mod Pathol · Pubmed #20305616.

ABSTRACT: Pancreatic endocrine tumors are rare diseases and devising a clinically effective prognostic stratification of patients is a major clinical challenge. This study aimed at assessing whether the tumor-node-metastasis (TNM)-based staging and proliferative activity-based grading recently proposed by the European NeuroEndocrine Tumors Society (ENETS) have clinical value. TNM was applied to 274 patients with histologically diagnosed pancreatic endocrine tumors operated from 1991 to 2005, with last follow-up at December 2007. According to World Health Organization (WHO) classification, 246 were well-differentiated neoplasms (51 benign, 56 uncertain behavior, 139 carcinomas) and 28 poorly differentiated carcinomas. Grading was based on Ki67 immunohistochemistry. Survival analysis not only ascertained the prognostic value of the TNM system but also highlighted that in the absence of nodal and distant metastasis, infiltration and tumor dimensions over 4 cm had prognostic significance. T parameters were then appropriately modified to reflect this weakness. The 5-year survival for modified TNM stages I, II, III and IV were 100, 93, 65 and 35%, respectively. Multivariate analysis identified TNM stages as independent predictors of death, in which stages II, III and IV showed a risk of death of 7, 29 and 58 times higher than stage I tumors (P<0.0001). Ki67-based grading resulted an independent predictor of survival with cut-offs at 5 and 20%. In conclusion, WHO classification assigns clinically significant diagnostic categories to pancreatic endocrine tumors that need prognostic stratification by applying a staging system. The ENETS-TNM provides the best option, but it requires some modifications to be fully functional. The modified TNM described in this study ameliorates the clinical applicability and prediction of outcome of the ENETS-TNM; it (i) assigns a risk of death proportional to the stage at the time of diagnosis, and (ii) allows a clinically based staging of patients, as the T parameters as modified permit their clinical-radiological recognition. Ki67-based grading discerns prognosis of patients with same stage diseases.

23 Article Parenchyma-preserving resections for small nonfunctioning pancreatic endocrine tumors. 2010

Falconi, Massimo / Zerbi, Alessandro / Crippa, Stefano / Balzano, Gianpaolo / Boninsegna, Letizia / Capitanio, Vanessa / Bassi, Claudio / Di Carlo, Valerio / Pederzoli, Paolo. ·Chirurgia Generale B (Pancreas Unit), Department of Surgery, University of Verona, Policlinico GB Rossi, Verona, Italy. massimo.falconi@univr.it ·Ann Surg Oncol · Pubmed #20162460.

ABSTRACT: BACKGROUND: Parenchyma-preserving resections (PPRs), including enucleation and middle pancreatectomy (MP), are accepted procedures for insulinomas, but their role in the treatment of nonfunctioning pancreatic endocrine tumors (NF-PETs) is debated. The aim of this study was to evaluate perioperative and long-term outcomes after PPRs for NF-PETs. METHODS: All patients who underwent PPRs for NF-PETs between 1990 and 2005 were included. Patients with multiple endocrine neoplasia type 1 were excluded. RESULTS: Overall, 50 patients (23 men, 27 women, median age 59 years) underwent 26 enucleations and 24 MP. A total of 58% of NF-PETs were incidentally discovered. Median size of the tumors was 13.5 mm with no preoperative suspicion of malignancy in all patients. Overall morbidity and pancreatic fistula rates were 58 and 50%, respectively. Reoperation rate was 4%, with no mortality. Postoperative complications were higher in the MP group. At pathology, there were 34 (68%) benign lesions, 13 (26%) neoplasms of uncertain behavior, and 3 (6%) well-differentiated carcinomas. Forty-one patients (82%) had tumors < or =2 cm in size. Only eight patients (16%) had at least one lymph node removed. After a median follow-up of 58 months, no patient died of disease. Overall, four patients (8%) experienced tumor recurrence after a mean of 68 months. The incidence of exocrine/endocrine insufficiency was 8%. CONCLUSIONS: PPRs are generally safe and effective procedures for treating small NF-PETs. However, better selection criteria must be identified, and lymph node sampling should be performed routinely to avoid understaging. Long-term follow-up evaluation (>5 years) is of paramount importance given the possible risk of late recurrence.

24 Minor Implications of the new histological classification (WHO 2010) for pancreatic neuroendocrine neoplasms. 2012

Crippa, S / Partelli, S / Boninsegna, L / Falconi, M. · ·Ann Oncol · Pubmed #22753260.

ABSTRACT: -- No abstract --