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Pancreatic Neoplasms: HELP
Articles by Domenico Tamburrino
Based on 27 articles published since 2010
(Why 27 articles?)
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Between 2010 and 2020, D. Tamburrino wrote the following 27 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Statin use improves survival in patients with pancreatic ductal adenocarcinoma: A meta-analysis. 2020

Tamburrino, Domenico / Crippa, Stefano / Partelli, Stefano / Archibugi, Livia / Arcidiacono, Paolo Giorgio / Falconi, Massimo / Capurso, Gabriele. ·Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; PhD Candidate in Digestive Oncology, "La Sapienza University" Rome, Italy. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; Vita Salute University, Milan, Italy. · Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy. · Vita Salute University, Milan, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy. · Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Milan, Italy. Electronic address: capurso.gabriele@hsr.it. ·Dig Liver Dis · Pubmed #32113888.

ABSTRACT: BACKGROUND: Previous studies on statins' effect on survival of patients with pancreatic ductal adenocarcinoma (PDAC) report conflicting results. AIMS: To evaluate the association between statin use and PDAC patients' survival. METHODS: A systematic review and meta-analysis was performed including case-control, cohort studies and randomized controlled trials assessing the association between statin use and survival in PDAC patients. Pooled HRs with 95%CIs were calculated using random effects model; publication bias was assessed through Begg and Mazumdar test and heterogeneity by I RESULTS: 14 studies with 33,137 PDAC patients, 40% under statins, were included. Statins use was associated to a reduced death risk (HR 0.871; 95%CI: 0.819; 0.927; p = 0.0001) suggesting a protective effect, homogeneous for different geographic areas. This effect was significant in surgically resected patients (HR 0.50; 95%CI: 0.32; 0.76; p = 0.001) but not in those with advanced disease (HR 0.78; 95%CI: 0.59; 1.02; p = 0.07). In studies providing information on statin type, only rosuvastatin resulted associated to a reduced risk of death (HR 0.88; 95%CI: 0.81; 0.96; p = 0.004). CONCLUSIONS: Statins use is significantly associated with a reduced risk of death in resected PDAC patients. This finding has to be considered with caution due to publication bias and the availability of only few studies for sensitivity analyses.

2 Review Systematic review and meta-analysis of prognostic role of splenic vessels infiltration in resectable pancreatic cancer. 2018

Crippa, Stefano / Cirocchi, Roberto / Maisonneuve, Patrick / Partelli, Stefano / Pergolini, Ilaria / Tamburrino, Domenico / Aleotti, Francesca / Reni, Michele / Falconi, Massimo. ·Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. · Department of General and Oncologic Surgery, University of Perugia, St. Maria Hospital, Terni, Italy. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · Department of Surgery, Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy. · Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy; Department of Oncology, San Raffaele Scientific Institute, Milan, Italy. · Division of Pancreatic Surgery, Vita e Salute University, San Raffaele Scientific Institute, Milan, Italy; Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. Electronic address: falconi.massimo@hsr.it. ·Eur J Surg Oncol · Pubmed #29183639.

ABSTRACT: BACKGROUND: Identification of factors associated with dismal survival after surgery in resectable pancreatic ductal adenocarcinoma is important to select patients for neoadjuvant treatment. The present meta-analysis aimed to compare the results of distal pancreatectomy for resectable adenocarcinoma of the pancreatic body-tail with and without splenic vessels infiltration. METHODS: A systematic search was performed of PubMed, Embase and the Cochrane Library in accordance with PRISMA guidelines. The inclusion criteria were studies including patients who underwent distal pancreatectomy for pancreatic cancer with or without splenic vessels infiltration. 5-year overall survival (OS) was the primary outcomes. Meta-analysis was carried out applying time-to-event method. RESULTS: Six articles with 423 patients were analysed. Patients with pathological splenic artery invasion had a worse survival compared with those without infiltration (Hazard ratio 1.76, 95% CI 1.36-2.28; P < 0.0001). A similar results was found when considering pathological splenic vessels infiltration, showing that survival was significantly poorer when splenic vein infiltration was present (Hazard ratio 1.51, 95% CI 1.19-1.93; P = 0.0009). CONCLUSIONS: This meta-analysis showed worse survival for patients with splenic vessels infiltration undergoing distal pancreatectomy for pancreatic cancer. Splenic vessels infiltration represents the stigmata of a more aggressive disease, although resectable.

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 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.

5 Review Selection criteria in resectable pancreatic cancer: a biological and morphological approach. 2014

Tamburrino, Domenico / Partelli, Stefano / Crippa, Stefano / Manzoni, Alberto / Maurizi, Angela / Falconi, Massimo. ·Domenico Tamburrino, Stefano Partelli, Stefano Crippa, Alberto Manzoni, Angela Maurizi, Massimo Falconi, Pancreatic Surgery Unit, Department of Surgery, Polytechnic University of Marche Region, 60126 Ancona-Torrette, Italy. ·World J Gastroenterol · Pubmed #25170205.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDA) remains one of the most aggressive tumors with a low rate of survival. Surgery is the only curative treatment for PDA, although only 20% of patients are resectable at diagnosis. During the last decade there was an improvement in survival in patients affected by PDA, possibly explained by the advances in cancer therapy and by improve patient selection by pancreatic surgeons. It is necessary to select patients not only on the basis of surgical resectability, but also on the basis of the biological nature of the tumor. Specific preoperative criteria can be identified in order to select patients who will benefit from surgical resection. Duration of symptoms and level of carbohydrate antigen 19.9 in resectable disease should be considered to avoid R1 resection and early relapse. Radiological assessment can help surgeons to distinguish resectable disease from borderline resectable disease and locally advanced pancreatic cancer. Better patient selection can increase survival rate and neoadjuvant treatment can help surgeons select patients who will benefit from surgery.

6 Review Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas. 2014

Paini, Marina / Crippa, Stefano / Partelli, Stefano / Scopelliti, Filippo / Tamburrino, Domenico / Baldoni, Andrea / Falconi, Massimo. ·Marina Paini, Domenico Tamburrino, Department of Surgery, University of Verona, 37134 Verona (VR), Italy. ·World J Gastroenterol · Pubmed #25110429.

ABSTRACT: Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management.

7 Review GEP-NETS update: a review on surgery of gastro-entero-pancreatic neuroendocrine tumors. 2014

Partelli, Stefano / Maurizi, Angela / Tamburrino, Domenico / Baldoni, Andrea / Polenta, Vanessa / Crippa, Stefano / Falconi, Massimo. ·Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy. · Pancreatic Surgery UnitUniversità Politecnica delle Marche, Via Conca, 71, 60126 Ancona, ItalyDepartment of SurgeryUniversity of Verona, Verona, Italy m.falconi@univpm.it. ·Eur J Endocrinol · Pubmed #24920289.

ABSTRACT: The incidence of neuroendocrine tumors (NETs) has increased in the last decades. Surgical treatment encompasses a panel of approaches ranging from conservative procedures to extended surgical resection. Tumor size and localization usually represent the main drivers in the choice of the most appropriate surgical resection. In the presence of small (<2 cm) and asymptomatic nonfunctioning NETs, a conservative treatment is usually recommended. For localized NETs measuring above 2 cm, surgical resection represents the cornerstone in the management of these tumors. As they are relatively biologically indolent, an extended resection is often justified also in the presence of advanced NETs. Surgical options for NET liver metastases range from limited resection up to liver transplantation. Surgical choices for metastatic NETs need to consider the extent of disease, the grade of tumor, and the presence of extra-abdominal disease. Any surgical procedures should always be balanced with the benefit of survival or relieving symptoms and patients' comorbidities.

8 Review Surgical management of pancreatic neuroendocrine neoplasms. 2014

Partelli, Stefano / Maurizi, Angela / Tamburrino, Domenico / Crippa, Stefano / Pandolfi, Silvia / Falconi, Massimo. ·Prof. Massimo Falconi, Department of Surgery,, Clinical Chirurgia del Pancreas,, Ospedali Riuniti,, Via Conca 71,, Torrette-Ancona 60126, Italy, T: +39 0715965781, F: +39 0712206024, m.falconi@univpm.it. ·Ann Saudi Med · Pubmed #24658547.

ABSTRACT: Pancreatic neuroendocrine neoplasms are relatively rare entities, representing approximately 1% to 2% of all pancreatic tumors. Owing to their rarity as well as their relatively indolent natural history, treatment approaches are not yet standardized. A formal pancreatic resection is usually mandatory for large and localized sporadic pancreatic tumors or in the presence of symptoms. However, in small and asymptomatic lesions, a conservative approach consisting in a careful wait-and-see policy is going to appear as more appropriate, particularly when, to remove the lesion, an aggressive surgical procedure is required, such as pancreaticoduodenectomy or distal splenopancreatectomy, depending on the localization of the tumor. Surgery has also a significant role in locally advanced and metastatic forms. In the setting of MEN 1 syndrome or Von-Hippel Lindau disease, the tumor size and the possible symptoms should be considered in the evaluation of a proper treatment.

9 Article Time to CA19-9 nadir: a clue for defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma. 2020

Reni, Michele / Peretti, Umberto / Zanon, Silvia / Macchini, Marina / Balzano, Gianpaolo / Mazza, Elena / Tamburrino, Domenico / Orsi, Giulia / Arcidiacono, Paolo Giorgio / Falconi, Massimo / Gianni, Luca. ·Department of Medical Oncology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. reni.michele@hsr.it. · Department of Medical Oncology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. · Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. · Università "Vita E Salute", Via Olgettina 58, 20132, Milan, Italy. ·Cancer Chemother Pharmacol · Pubmed #32157412.

ABSTRACT: BACKGROUND: Defining optimal treatment duration in patients with resectable pancreatic ductal adenocarcinoma (PDAC) receiving primary chemotherapy is an unmet need. The role of time to CA19-9 nadir and of nadir magnitude was explored in this study. PATIENTS AND METHODS: The databases of our institution's prospective trials were queried to speculate on the time to maximum chemotherapy response. Patients with pathologically proven, metastatic (N = 356) or non-metastatic non-resected (N = 163) PDAC and elevated baseline (> 34 UI/mL) CA19-9 were analyzed. Survival curves were estimated using the Kaplan-Meier method and compared by means of the log-rank test for analyses including at least 45 patients. Multivariable Cox proportional hazards model was used to estimate clinical features for their association with OS. All probability values were from two-sided tests. RESULTS: Time to CA19-9 nadir was ≥ 4 months in 184 of 346 (53%) metastatic and 121 of 163 (74%) non-metastatic patients (p = 0.002). The likelihood of a later nadir was higher with taxane-based chemotherapy as compared to taxane-free combinations (73% versus 56%; p = 0.02). Both metastatic and non-metastatic patients had significantly longer survival when nadir occurred later. Patients with a larger CA19-9 nadir magnitude had significantly longer survival. Metastatic patients with CA19-9 reduced by < 50%, 50-89%, or > 89% and had a median survival of 7.4, 9.8, and 14.7 months, respectively (p ≤ 0.001 for all comparisons). The corresponding figures for non-metastatic patients were 10.6; 17.0; and 18.7 months, respectively (p ≤ 0.02 for < 50% versus 50-89% or > 89%; p = 0.14 for 50-89% versus > 89%). Multivariable analyses showed that time to CA19-9 nadir but not CA19-9 nadir magnitude was independently predictive of survival. CONCLUSION: The present study suggests that a 4-6 months program might be a more suitable candidate for prospective assessment in comparison to shorter pre-defined period in patients who are candidates to surgery after primary chemotherapy.

10 Article Postoperative Outcomes and Functional Recovery After Preoperative Combination Chemotherapy for Pancreatic Cancer: A Propensity Score-Matched Study. 2019

Pecorelli, Nicolò / Pagnanelli, Michele / Cinelli, Lorenzo / Di Salvo, Francesca / Partelli, Stefano / Crippa, Stefano / Tamburrino, Domenico / Castoldi, Renato / Belfiori, Giulio / Reni, Michele / Falconi, Massimo / Balzano, Gianpaolo. ·Division of Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute, Milan, Italy. · Vita-Salute San Raffaele University, Milan, Italy. · Department of Medical Oncology, San Raffaele Scientific Institute, Milan, Italy. ·Front Oncol · Pubmed #31850203.

ABSTRACT:

11 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

12 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.

13 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.

14 Article Major postoperative complications after pancreatic resection for P-NETS are not associated to earlier recurrence. 2017

Valente, R / Lykoudis, P / Tamburrino, D / Inama, M / Passas, I / Toumpanakis, C / Luong, T V / Davidson, B / Imber, C / Malagò, M / Rahman, S H / Shankar, A / Sharma, D / Caplin, M / Fusai, G. ·Department of Hepatopancreatobiliary and Liver Transplantation Surgery, Royal Free and University College London, NW32QG, UK; Hepatopancreatobiliary Service, Barts Health NHS Trust, The Royal London Hospital, E1 1BZ, UK. Electronic address: r.valente@ucl.ac.uk. · Department of Hepatopancreatobiliary and Liver Transplantation Surgery, Royal Free and University College London, NW32QG, UK. · Neuroendocrine Tumour Unit, Royal Free and University College London, NW32QG, UK. · Histopathology Unit, Royal Free and University College London, NW32QG, UK. ·Eur J Surg Oncol · Pubmed #28821361.

ABSTRACT: BACKGROUND: The oncological impact of surgical complications has been studied in visceral and pancreatic cancer. AIM: To investigate the impact of complications on tumour recurrence after resections for pancreatic neuroendocrine tumours. METHODS: We have retrospectively analysed 105 consecutive resections performed at the Royal Free London Hospital from 1998 to 2014, and studied the long-term outcome of nil-minor (<3) versus major (≥3) Clavien-Dindo complications (CD) on disease-free (DFS) and overall survival (OS). RESULTS: The series accounted for 41 (39%) pancreaticoduodenectomies, two (1.9%) central, 48 (45.7%) distal pancreatectomies, eight (7.6%) enucleations, four (3.8%) total pancreatectomies. Sixteen (15.2%) were extended to adjacent organs, 13 (12.3%) to minor liver resections. Postoperative complications presented in 43 (40.1%) patients; CD grade 1 or 2 in 23 (21.9%), grades ≥3 in 20 (19%). Among 25 (23.8%) pancreatic fistulas, 14 (13.3%) were grades B or C. Thirty-four (32.4%) patients developed exocrine, and 31 (29.5%) endocrine insufficiency. Seven patients died during a median 27 (0-175) months follow up. Thirty-day mortality was 0.9%. OS was 94.1% at 5 years. Thirty tumours recurred within 11.7 (0.8-141.5) months. DFS was 44% at 5 years. At univariate analysis, high-grade complications were not associated with shorter DFS (p = 0.744). At multivariate analysis, no parameter was independent predictor for DFS or OS. The comparison of nil-minor versus major complications showed no DFS difference (p = 0.253). CONCLUSION: From our series, major complications after P-NETs resection are not associated to different disease recurrence; hence do not require different follow up or adjuvant regimens.

15 Article Active Surveillance Beyond 5 Years Is Required for Presumed Branch-Duct Intraductal Papillary Mucinous Neoplasms Undergoing Non-Operative Management. 2017

Crippa, Stefano / Pezzilli, Raffaele / Bissolati, Massimiliano / Capurso, Gabriele / Romano, Luigi / Brunori, Maria Paola / Calculli, Lucia / Tamburrino, Domenico / Piccioli, Alessandra / Ruffo, Giacomo / Fave, Gianfranco Delle / Falconi, Massimo. ·Department of Surgery, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Pancreas Translational &Clinical Research Center, Division of Pancreatic Surgery, Università Vita-Salute, San Raffaele Scientific Institute, Milan, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Division of Transplant Surgery, San Raffaele Scientific Institute, Milan, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, University Sapienza, Rome, Italy. · Department of Radiology, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Division of Gastroenterology, Sacro Cuore-Don Calabria Hospital, Negrar, Verona, Italy. · Department of Radiology, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Surgery, Università Politecnica delle Marche, Ancona, Italy. ·Am J Gastroenterol · Pubmed #28244498.

ABSTRACT: OBJECTIVES: To evaluate the results of active surveillance beyond 5 years in patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WF) and high-risk stigmata (HRS) undergoing non-operative management. METHODS: Patients with a minimum follow-up of 5 years who underwent surveillance with at least yearly magnetic resonance imaging were included. New onset of and predictors of WF/HRS during follow-up as well as long-term survival were analyzed. RESULTS: In all, 144 patients were followed for a median of 84 months. At diagnosis multifocal BD-IPMNs were found in 53% of cases and mean size of the largest cyst was 15.5 mm. Changes during follow-up were observed in 69 patients (48%). New onset of WF/HRS were observed in 26 patients (18%) but the rate of HRS was only 4%. WF and HRS developed after a median follow-up of 71 and 77.5 months from diagnosis, respectively, and without previous changes in 19/26 patients. Independent predictors of WF/HRS development were size at diagnosis>15 mm, increase in number of lesions, main pancreatic duct growth rate ≥0.2 mm/year, cyst growth rate >1 mm/year. Overall, the rate of pancreatic invasive malignancy was 2% and the 12-year disease-specific survival was 98.6%. CONCLUSIONS: Long-term nonoperative management is safe for BD-IPMNs without WF and HRS. Discontinuation of surveillance cannot be recommended since one out of six patients developed WF/HRS far beyond 5 years of surveillance and without previous relevant modifications. An intensification of follow-up should be considered after 5 years.

16 Article [Pancreatic cancer]. 2016

Falconi, Massimo / Tamburrino, Domenico / Buzzetti, Elena / Partelli, Stefano. ·Chirurgia del Pancreas, Pancreas Translational & Clinical Research Center, Ospedale San Raffaele, Università "Vita e Salute", Milano. · HPB and Liver Transplant Surgery, Royal Free Hospital, NHS Foundation Trust, London (UK). · UCL Institute for Liver and Digestive Health, Royal Free Hospital, NHS Foundation Trust, London (UK). ·Recenti Prog Med · Pubmed #27362726.

ABSTRACT: Pancreatic cancer is the fourth leading cause of death for neoplasm in western countries. Surgery still remains the treatment of choice although almost 80% of patients are not resectable at diagnosis because of liver metastases and the 5-year overall survival of patients treated with surgery is only (20%). During the last two decades we have witnessed an overall improvement in terms of survival, mostly due to the advances in therapy and strategies for a more accurate patient selection for surgery. Specific preoperative criteria, mostly linked to the biological features of the tumour, have been proposed to better identify those patients who will benefit from surgical resection, such as duration of symptoms and serum level of CA19-9 in resectable disease. Oncological therapy plays a central role in the management of pancreatic cancer. In patients undergone surgical resection, adjuvant therapy might increase the overall survival and reduce the rate of early relapse. Patients with locally advanced pancreatic cancer can be treated with neoadjuvant treatment. Chemotherapy or chemoradiotherapy are usually used with the aim to downstage the disease but whether one specific strategy or drug is the treatment of choice is still under debate.

17 Article Active Surveillance versus Surgery of Nonfunctioning Pancreatic Neuroendocrine Neoplasms ≤2 cm in MEN1 Patients. 2016

Partelli, Stefano / Tamburrino, Domenico / Lopez, Caroline / Albers, Max / Milanetto, Anna Caterina / Pasquali, Claudio / Manzoni, Marco / Toumpanakis, Christos / Fusai, Giuseppe / Bartsch, Detlef / Falconi, Massimo. ·Pancreatic Surgery Unit, Department of Internal Medicine, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy. ·Neuroendocrinology · Pubmed #26731608.

ABSTRACT: BACKGROUND: The aim of this study was to evaluate the efficacy of conservative treatment for nonfunctioning pancreatic neuroendocrine neoplasms (NF-PNEN) ≤2 cm in multiple endocrine neoplasia type 1 (MEN1)-affected patients compared with surgical treatment. METHODS: The databases of 4 tertiary referral institutions (San Raffaele Scientific Institute, Milan; Philipps-Universität Marburg, Marburg; University of Padua, Padua; Royal Free Hospital, London) were analyzed. A comparison of conservative management and surgery at initial diagnosis of NF-PNEN ≤2 cm between 1997 and 2013 was performed. RESULTS: Overall, 27 patients (45%) underwent up-front surgery and 33 patients (55%) were followed up after the initial diagnosis. A higher proportion of patients in the surgery group were female (70 vs. 33%, p = 0.004). Patients were mainly operated on in the period 1997-2007 as compared with the period 2008-2013 (n = 17; 63 vs. 37%; p = 0.040). The rate of multifocal tumors was higher in the surgery group (n = 24; 89%) than in the 'no surgery' group (n = 22; 67%; p = 0.043). After a median follow-up of 126 months, 1 patient deceased due to postoperative complications within 30 days after surgery. The 5-, 10-, and 15-year progression-free survival (PFS) rates were 63, 39, and 10%, respectively. The median PFS was similar in the two groups. Overall, 13 patients (32.5%) were operated on after initial surgical or conservative treatment. The majority of the surgically treated patients had stage 1 (77.5%), T1 (77.5%), and G1 (85%) tumors. CONCLUSIONS: NF-PNEN ≤2 cm in MEN1 patients are indolent neoplasms posing a low oncological risk. Surgical treatment of these tumors at initial diagnosis is rarely justified in favor of conservative treatment.

18 Article Long-Term Outcomes of Surgical Management of Pancreatic Neuroendocrine Tumors with Synchronous Liver Metastases. 2015

Partelli, Stefano / Inama, Marco / Rinke, Anja / Begum, Nehara / Valente, Roberto / Fendrich, Volker / Tamburrino, Domenico / Keck, Tobias / Caplin, Martyn E / Bartsch, Detlef / Thirlwell, Christina / Fusai, Giuseppe / Falconi, Massimo. ·Pancreatic Surgery Unit, University Hospital of Ancona, Ancona, Italy. ·Neuroendocrinology · Pubmed #26043944.

ABSTRACT: BACKGROUND: The value of surgical resection in the management of pancreatic neuroendocrine tumors (PNET) with liver metastases (LM) is still debated. The aim of this study was to evaluate the outcomes of surgery of PNET with LM. METHODS: Patients with PNET with synchronous LM between 2000 and 2011 from 4 high-volume institutions were included. The patients were divided into 3 groups: curative resection, palliative resection, and no resection. RESULTS: Overall, 166 patients were included. Eighteen patients (11%) underwent curative resection, 73 patients (43%) underwent palliative resection, and 75 patients (46%) underwent conservative treatment. The median overall survival (OS) from the time of diagnosis was 73 months. Patients who underwent curative resection had a significantly better median OS from the initial diagnosis compared with those who underwent palliative resection and those who were conservatively treated (97 vs. 89 vs. 36 months, p = 0.0001). The median OS from the time of diagnosis in those patients who underwent radical or palliative resection was 97 months, with a 5-year survival rate of 76%. On multivariate analysis, factors associated with OS from the time of diagnosis were the presence of bilobar metastases, tumor grading, and curative resection in a first model. On a second model, curative or palliative surgery was an independent predictor of OS. Among 91 patients who underwent surgery, the presence of pancreatic neuroendocrine carcinoma G3 was the only factor independently associated with a poorer survival after surgery (median OS: 35 vs. 97 months, p < 0.0001). CONCLUSIONS: Patients with LM from PNET benefit from surgical resection, although surgery should be reserved to well- or moderately differentiated forms.

19 Article Evaluation of a predictive model for pancreatic fistula based on amylase value in drains after pancreatic resection. 2014

Partelli, Stefano / Tamburrino, Domenico / Crippa, Stefano / Facci, Enrico / Zardini, Claudio / Falconi, Massimo. ·Department of Surgery, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy. · Department of Surgery, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy. Electronic address: m.falconi@univpm.it. ·Am J Surg · Pubmed #25001423.

ABSTRACT: BACKGROUND: Amylase value in drains (AVD) is a predictor of pancreatic fistula (PF). We evaluated the accuracy of an AVD-based model. METHODS: Two hundred thirty-one patients underwent pancreatoduodenectomy with pancreaticojejunostomy (PDPJ) or pancreatoduodenectomy with duct-to-mucosa (PDDTM) and distal pancreatectomy (DP). Patients with AVD greater than 5,000 U/L on postoperative day (POD) 1 underwent AVD measurement on POD5. RESULTS: Sensitivity and specificity of POD1 AVD greater than 5,000 in predicting PF were 71% and 90%, respectively. The sensitivity and specificity of POD5 AVD greater than 200 were 90% and 83%, respectively. AVD greater than 1,000 (for PDPJ) and 2,000 U/L (PDDTM and DP) represented the most accurate cutoffs on POD1. AVD greater than 200 (PDPJ), 300 (PDDTM), and 50 U/L (DP) represented the cutoffs with the highest sensitivity in predicting PF on POD5. CONCLUSION: AVD-based model for predicting PF after pancreatic resection is an accurate tool, although AVD cutoffs should be evaluated for each type of operation.

20 Article The role of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in resectable pancreatic cancer. 2014

Crippa, Stefano / Salgarello, Matteo / Laiti, Silvia / Partelli, Stefano / Castelli, Paola / Spinelli, Antonello E / Tamburrino, Domenico / Zamboni, Giuseppe / Falconi, Massimo. ·Division of Pancreatic Surgery, Department of Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy. · Department of Nuclear Medicine, University of Verona, Negrar, Italy. · Residency Programme in Surgery, University of Verona, Italy. · Department of Pathology, Ospedale Sacro Cuore-Don Calabria, Negrar, Italy. · Department of Medical Physics and Experimental Imaging, San Raffaele Scientific Institute, Milan, Italy. · Division of Pancreatic Surgery, Department of Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy. Electronic address: m.falconi@univpm.it. ·Dig Liver Dis · Pubmed #24721105.

ABSTRACT: BACKGROUND: The role of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in pancreatic ductal adenocarcinoma is debated. We retrospectively assessed the value of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in addition to conventional imaging as a staging modality in pancreatic cancer. METHODS: (18)Fluoro-deoxyglucose positron emission tomography/computed tomography was performed in 72 patients with resectable pancreatic carcinoma after multi-detector computed tomography positron emission tomography was considered positive for a maximum standardized uptake value >3. RESULTS: Overall, 21% of patients had a maximum standardized uptake value ≤ 3, and 60% of those had undergone neoadjuvant treatment (P=0.0001). Furthermore, 11% of patients were spared unwarranted surgery since positron emission tomography/computed tomography detected metastatic disease. All liver metastases were subsequently identified with contrast-enhanced ultrasound. Sensitivity and specificity of positron emission tomography/computed tomography for distant metastases were 78% and 100%. The median CA19.9 concentration was 48.8 U/mL for the entire cohort and 292 U/mL for metastatic patients (P=0.112). CONCLUSIONS: The widespread application of (18)fluoro-deoxyglucose positron emission tomography/computed tomography in patients with resectable pancreatic carcinoma seems not justified. It should be considered in selected patients at higher risk of metastatic disease (i.e. CA19.9>200 U/mL) after undergoing other imaging tests. Neoadjuvant treatment is significantly associated with low metabolic activity, limiting the value of positron emission tomography in this setting.

21 Article Incidental diagnosis as prognostic factor in different tumor stages of nonfunctioning pancreatic endocrine tumors. 2014

Crippa, Stefano / Partelli, Stefano / Zamboni, Giuseppe / Scarpa, Aldo / Tamburrino, Domenico / Bassi, Claudio / Pederzoli, Paolo / Falconi, Massimo. ·Department of Surgery, Policlinico GB Rossi, University of Verona, Verona, Italy; Department of Surgery, Ospedale Sacro Cuore-Don Calabria, Negrar (VR), Italy. · Department of Pathology, Policlinico GB Rossi, University of Verona, Verona, Italy; Department of Pathology, Ospedale Sacro Cuore-Don Calabria, Negrar (VR), Italy. · Department of Pathology, Policlinico GB Rossi, University of Verona, Verona, Italy. · Department of Surgery, Policlinico GB Rossi, University of Verona, Verona, Italy. · Department of Surgery, Policlinico GB Rossi, University of Verona, Verona, Italy. Electronic address: m.falconi@univpm.it. ·Surgery · Pubmed #24646958.

ABSTRACT: BACKGROUND: Incidentally discovered nonfunctioning pancreatic endocrine tumors (NF-pNETs) increasingly are being detected, and their management is debated. Moreover, the prognostic importance of incidental diagnosis for locally advanced or metastatic NF-pNETs is unknown. The aim of this study is to analyze the outcomes of incidentally discovered/symptomatic NF-pNETs stratified by tumor stage. A preliminary experience with nonoperative treatment of incidental NF-pNETs is reported. METHODS: Consecutive patients with symptomatic/incidental NF-PETs observed between 1990 and 2009 were analyzed, with different tumor stages considered. Nonoperative management of incidental NF-pNETs was evaluated. RESULTS: Among 355 patients with NF-pNETs, the diagnosis was incidental in 124 (35%). Incidental NF-pNETs were associated more commonly with lower tumor stages compared with symptomatic tumors (P < .0001), but 30% of incidental NF-pNETs were stage III-IV. Incidental NF-pNETs had greater rates of radical resections and of R0 margins (P < .0001). Five-year progression-free survival (PFS) was 83% and 32% for incidental and symptomatic NF-pNETs, respectively (P < .0001). Five-year PFS was better for incidental NF-pNETs compared with symptomatic tumors for each tumor stage, including stage III (69% vs 27%, P < .0001) and stage IV (60% vs 17%, P = .112). After a median follow-up of 36 months, there was no tumor progression in 12 patients who underwent nonoperative management of incidental NF-pNETs. CONCLUSION: A total of 30% of incidental NF-pNETs present with stage III-IV disease. PFS is much greater for incidental NF-pNETs compared with symptomatic patients, and this difference is evident also for stage III-IV tumors, suggesting that absence of symptoms may indicate a less-aggressive disease. Nonoperative management can be an alternative to surgery in selected incidental NF-pNETs.

22 Article The natural history of a branch-duct intraductal papillary mucinous neoplasm of the pancreas. 2014

Crippa, Stefano / Partelli, Stefano / Tamburrino, Domenico / Falconi, Massimo. ·Division of Surgery, Ospedale "Sacro Cuore-Don Calabria," Negrar (VR), Italy; Department of Surgery, University of Verona, Verona, Italy; Division of Pancreatic and Digestive Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy. Electronic address: ste.crippa@libero.it. · Division of Surgery, Ospedale "Sacro Cuore-Don Calabria," Negrar (VR), Italy; Department of Surgery, University of Verona, Verona, Italy; Division of Pancreatic and Digestive Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy. · Division of Surgery, Ospedale "Sacro Cuore-Don Calabria," Negrar (VR), Italy; Department of Surgery, University of Verona, Verona, Italy. ·Surgery · Pubmed #23261026.

ABSTRACT: -- No abstract --

23 Article Observational study of natural history of small sporadic nonfunctioning pancreatic neuroendocrine tumors. 2013

Gaujoux, Sébastien / Partelli, Stefano / Maire, Frédérique / D'Onofrio, Mirko / Larroque, Béatrice / Tamburrino, Domenico / Sauvanet, Alain / Falconi, Massimo / Ruszniewski, Philippe. ·MD, Department of Hepatobiliary and Pancreatic Surgery, Hospital Beaujon, 100, Boulevard du Général Leclerc, 92110 Clichy, France. alain.sauvanet@bjn.aphp.fr. ·J Clin Endocrinol Metab · Pubmed #24057286.

ABSTRACT: CONTEXT: Asymptomatic sporadic nonfunctioning, well-differentiated pancreatic neuroendocrine tumors (NF-PNETs) are increasingly diagnosed, and their management is controversial because of their overall good but heterogeneous prognosis. OBJECTIVE: The objective of the study was to assess the natural history of asymptomatic sporadic NF-PNETs smaller than 2 cm in size and the risk-benefit balance of nonoperative management. EXPERIMENTAL DESIGN: From January 2000 to June 2011, 46 patients with proven asymptomatic sporadic NF-PNETs smaller than 2 cm in size were followed up for at least 18 months with serial imaging in tertiary referral centers. RESULTS: Patients were mainly female (65%), with a median age of 60 years. Tumors were mainly located in the pancreatic head (52%), with a median lesion size of 13 mm (range 9-15). After a median follow-up of 34 months (range 24-52) and an average of four (range 3-6) serial imaging sessions, distant or nodal metastases appeared on the imaging in none of the patients. In six patients (13%), a 20% or greater increase in size was observed. Overall median tumor growth was 0.12 mm per year, and neither patients nor tumor characteristics were found to be significant predictors of tumor growth. Overall, eight patients (17%) underwent surgery after a median time from initial evaluation of 41 months (range 27-58); all resected lesions were European Neuroendocrine Tumor Society T stage 1 (n = 7) or 2 (n = 1), grade 1, node negative, with neither vascular nor peripancreatic fat invasion. CONCLUSIONS: In selected patients, nonoperative management of asymptomatic sporadic NF-PNETs smaller than 2 cm in size is safe. Larger and prospective multicentric studies with long-term follow-up are now needed to validate this wait-and-see policy.

24 Article Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence. 2013

Campana, Davide / Capurso, Gabriele / Partelli, Stefano / Nori, Francesca / Panzuto, Francesco / Tamburrino, Domenico / Cacciari, Giulia / Delle Fave, Gianfranco / Falconi, Massimo / Tomassetti, Paola. ·Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy. davide.campana@unibo.it ·Eur J Nucl Med Mol Imaging · Pubmed #23619938.

ABSTRACT: PURPOSE: Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. METHODS: Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). RESULTS: A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with (90)Y or (177)Lu. The objective response rate was 27.5% (partial response, PR), while 50.7% had stable disease and 23.2% had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. CONCLUSION: Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided.

25 Article Pancreatic tumors and immature immunosuppressive myeloid cells in blood and spleen: role of inhibitory co-stimulatory molecules PDL1 and CTLA4. An in vivo and in vitro study. 2013

Basso, Daniela / Fogar, Paola / Falconi, Massimo / Fadi, Elisa / Sperti, Cosimo / Frasson, Chiara / Greco, Eliana / Tamburrino, Domenico / Teolato, Sara / Moz, Stefania / Bozzato, Dania / Pelloso, Michela / Padoan, Andrea / De Franchis, Giuseppe / Gnatta, Elisa / Facco, Monica / Zambon, Carlo-Federico / Navaglia, Filippo / Pasquali, Claudio / Basso, Giuseppe / Semenzato, Gianpietro / Pedrazzoli, Sergio / Pederzoli, Paolo / Plebani, Mario. ·Department of Medicine, University of Padova, Padova, Italy. daniela.basso@sanita.padova.it ·PLoS One · Pubmed #23359812.

ABSTRACT: BACKGROUND: Blood and spleen expansion of immature myeloid cells (IMCs) might compromise the immune response to cancer. We studied in vivo circulating and splenic T lymphocyte and IMC subsets in patients with benign and malignant pancreatic diseases. We ascertained in vitro whether pancreatic adenocarcinoma (PDAC)-associated IMC subsets are induced by tumor-derived soluble factors and whether they are immunosuppressive focusing on the inhibitory co-stimulatory molecules PDL1 and CTLA4. METHODOLOGY AND PRINCIPAL FINDINGS: 103 pancreatic and/or splenic surgical patients were enrolled including 52 PDAC, 10 borderline and 10 neuroendocrine tumors (NETs). Lymphocytes and IMCs were analysed by flow cytometry in blood, in spleen and in three PDAC cell conditioned (CM) or non conditioned PBMC. PDL1 and CTLA4 were studied in 30 splenic samples, in control and conditioned PBMC. IMCs were FACS sorted and co-coltured with allogenic T lymphocytes. In PDAC a reduction was found in circulating CD8(+) lymphocytes (p = 0.004) and dendritic cells (p = 0.01), which were reduced in vitro by one PDAC CM (Capan1; p = 0.03). Blood myeloid derived suppressive cells (MDSCs) CD33(+)CD14(-)HLA-DR(-) were increased in PDAC (p = 0.022) and were induced in vitro by BxPC3 CM. Splenic dendritic cells had a higher PDL1 expression (p = 0.007), while CD33(+)CD14(+)HLA-DR(-) IMCs had a lower CTLA4 expression (p = 0.029) in PDAC patients. In vitro S100A8/A9 complex, one of the possible inflammatory mediators of immune suppression in PDAC, induced PDL1 (p = 0.018) and reduced CTLA4 expression (p = 0.028) among IMCs. IMCs not expressing CTLA4 were demonstrated to be immune suppressive. CONCLUSION: In PDAC circulating dendritic and cytotoxic T cells are reduced, while MDSCs are increased and this might favour tumoral growth and progression. The reduced CTLA4 expression found among splenic IMCs of PDAC patients was demonstrated to characterize an immune suppressive phenotype and to be consequent to the direct exposure of myeloid cells to pancreatic cancer derived products, S100A8/A9 complex in particular.

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