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Pancreatic Neoplasms: HELP
Articles by Giovanni Marchegiani
Based on 68 articles published since 2010
(Why 68 articles?)
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Between 2010 and 2020, G. Marchegiani wrote the following 68 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. 2016

Adsay, Volkan / Mino-Kenudson, Mari / Furukawa, Toru / Basturk, Olca / Zamboni, Giuseppe / Marchegiani, Giovanni / Bassi, Claudio / Salvia, Roberto / Malleo, Giuseppe / Paiella, Salvatore / Wolfgang, Christopher L / Matthaei, Hanno / Offerhaus, G Johan / Adham, Mustapha / Bruno, Marco J / Reid, Michelle D / Krasinskas, Alyssa / Klöppel, Günter / Ohike, Nobuyuki / Tajiri, Takuma / Jang, Kee-Taek / Roa, Juan Carlos / Allen, Peter / Fernández-del Castillo, Carlos / Jang, Jin-Young / Klimstra, David S / Hruban, Ralph H / Anonymous6721124. ·*Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA †Department of Pathology, Massachusetts General Hospital, Boston, MA ‡Department of Pathology, Tokyo Women's Medical University, Tokyo, Japan §Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY ¶Department of Pathology, University of Verona, Verona, Italy ||Department of Surgery, Massachusetts General Hospital, Boston, MA **Department of Surgery, University of Verona, Verona, Italy ††Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD ‡‡Departments of Surgery, University of Bonn, Bonn, Germany §§Departments of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands ¶¶Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France ||||Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands ***Departments of Pathology, Technical University, Munich, Germany †††Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan ‡‡‡Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan §§§Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea ¶¶¶Department of Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile ||||||Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY ****Department of Surgery, Massachusetts General Hospital, Boston, MA ††††Department of Surgery, Seoul National University Hospital, Seoul, Korea ‡‡‡‡Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD. ·Ann Surg · Pubmed #25775066.

ABSTRACT: BACKGROUND: There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN: An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. RESULTS: (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤ 0.5, > 0.5-≤ 1, > 1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic). CONCLUSIONS: These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.

2 Review The Clinical Management of Main Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas. 2019

Dal Borgo, Chiara / Perri, Giampaolo / Borin, Alex / Marchegiani, Giovanni / Salvia, Roberto / Bassi, Claudio. ·Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italygiamperri@hotmail.it. ·Dig Surg · Pubmed #29421807.

ABSTRACT: BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas comprise a heterogeneous group of intraductal mucin-producing neoplasms representing a typical adenoma-to-carcinoma sequence. The involvement of the main pancreatic duct (MPD) is a feature of paramount importance, directly related to a more aggressive biology and a higher malignancy rate. METHOD: We review and discuss the clinical management of IPMNs with a MPD involvement, recalling the different consensus guidelines and addressing recent controversies in literature, presenting the current clinical practice in Verona Pancreas Institute. RESULTS: All the aspects of surgical management were discussed, from the indication for surgery to the intraoperative management and the follow-up strategies. CONCLUSION: The management of presumed IPMNs involving the MPD at our Institution is in line with the International Association of Pancreatology 2012 guidelines, revised in 2016. Surgical resection proposed should achieve the complete removal of the tumor with negative margins. Despite a good prognosis in terms of survival of overall resected main duct intraductal papillary mucinous neoplasms, follow-up should not be discontinued.

3 Review Surveillance of Cystic Lesions of the Pancreas: Whom and How to Survey? 2018

Andrianello, Stefano / Falconi, Massimo / Salvia, Roberto / Crippa, Stefano / Marchegiani, Giovanni. ·Pancreatic Surgery Unit of the Department of Surgery, Verona University Hospital, Verona, Italy. · Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy. ·Visc Med · Pubmed #30140686.

ABSTRACT: The sudden prevalence increase of pancreatic cystic neoplasms (PCN) related to the use of cross-sectional imaging has raised several concerns. Even if there is a tangible risk of progression towards pancreatic cancer (PC), surgical resection cannot be offered to all patients due to the high risk of morbidity and mortality. Available guidelines are useful tools to identify patients at higher risk for harboring cancer thanks to their sensitivity. Because of their low specificity, however, such a risk is often overestimated. Recent evidence deriving from large observational series of surveilled patients suggests that the overall risk of PC is low. A large proportion of patients affected by PCN can be safely observed over time. Several follow-up schedules have been proposed in guidelines but none of them proved to be the most cost-effective. Moreover, it must still be demonstrated that any surveillance protocol can be associated with a reduction in PC-related mortality. By now, with most studies reporting a lifelong risk of malignancy, the only evidence-based recommendation regarding surveillance is that follow-up should never be discontinued as repeated observations are crucial for PC risk stratification.

4 Review Pancreatic Cancer in the Era of Neoadjuvant Therapy: A Narrative Overview. 2018

Casciani, Fabio / Marchegiani, Giovanni / Malleo, Giuseppe / Bassi, Claudio / Salvia, Roberto. · ·Chirurgia (Bucur) · Pubmed #29981662.

ABSTRACT: Pancreatic adenocarcinoma is an aggressive systemic disease with around 30% of patient presenting locally advanced disease at diagnosis and being not candidate to surgical resection. Pioneering experiences with neoadjuvant treatment for locally advanced pancreatic cancer (LAPC) were undertaken more than 25 years ago and this strategy kept on gaining consensus over time. In recent years two main breakthroughs have been done: first, clear definitions of resectable, borderline resectable and locally advanced unresectable disease were released, and, soon after, two different chemotherapy regimens (namely, FOLFIRINOX and Gemcitabine plus Nab-Paclitaxel) were introduced in the clinical practice for LAPC after their effectiveness in metastatic patients was demonstrated. This article reviews papers regarding the administration of neoadjuvant chemotherapy, with or without radiation therapy, published from 2011 through 2017 with particular significance been given to reported results in term of resection rates, complete resection (R0) rates and Overall Survival, and briefly summarizes recommendations provided by the most recent guidelines for the treatment of non-metastatic pancreatic cancer.

5 Review Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: A systematic review and proportion meta-analysis of screening results. 2018

Paiella, Salvatore / Salvia, Roberto / De Pastena, Matteo / Pollini, Tommaso / Casetti, Luca / Landoni, Luca / Esposito, Alessandro / Marchegiani, Giovanni / Malleo, Giuseppe / De Marchi, Giulia / Scarpa, Aldo / D'Onofrio, Mirko / De Robertis, Riccardo / Pan, Teresa Lucia / Maggino, Laura / Andrianello, Stefano / Secchettin, Erica / Bonamini, Deborah / Melisi, Davide / Tuveri, Massimiliano / Bassi, Claudio. ·General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. Electronic address: salvatore.paiella@univr.it. · General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Gastroenterology B Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy; ARC-NET Research Center, University and Hospital Trust of Verona, Verona, Italy. · Department of Radiology, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Radiology, Casa di Cura Pederzoli Hospital, Peschiera del Garda, Italy. · Oncology Unit, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. ·Pancreatology · Pubmed #29709409.

ABSTRACT: BACKGROUND/OBJECTIVES: Screening/surveillance programs for pancreatic cancer (PC) in familial high-risk individuals (FPC-HRI) have been widely reported, but their merits remain unclear. The data reported so far are heterogeneous-especially in terms of screening yield. We performed a systematic review and meta-analysis of currently available data coming from screening/surveillance programs to evaluate the proportion of screening goal achievement (SGA), overall surgery and unnecessary surgery. METHODS: We searched MEDLINE, Embase, PubMed and the Cochrane Library database from January 2000 to December 2016to identify studies reporting results of screening/surveillance programs including cohorts of FPC-HRI. The main outcome measures were weighted proportion of SGA, overall surgery, and unnecessary surgery among the FPC-HRI cohort, using a random effects model. SGA was defined as any diagnosis of resectable PC, PanIN3, or high-grade dysplasia intraductal papillary mucinous neoplasm (HGD-IPMN). Unnecessary surgery was defined as any other final pathology. RESULTS: In a meta-analysis of 16 studies reporting on 1551 FPC-HRI cases, 30 subjects (1.82%), received a diagnosis of PC, PanIN3 or HGD-IPMNs. The pooled proportion of SGA was 1.4%(95% CI 0.8-2, p < 0.001, I CONCLUSIONS: The weighted proportion of SGA of screening/surveillance programs published thus far is excellent. However, the probability of receiving surgery during the screening/surveillance program is non-negligible, and unnecessary surgery is a potential negative outcome.

6 Review Systematic review, meta-analysis, and a high-volume center experience supporting the new role of mural nodules proposed by the updated 2017 international guidelines on IPMN of the pancreas. 2018

Marchegiani, Giovanni / Andrianello, Stefano / Borin, Alex / Dal Borgo, Chiara / Perri, Giampaolo / Pollini, Tommaso / Romanò, Giorgia / D'Onofrio, Mirko / Gabbrielli, Armando / Scarpa, Aldo / Malleo, Giuseppe / Bassi, Claudio / Salvia, Roberto. ·General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Radiology, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Gastroenterology and Digestive Endoscopy, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Pathology, ARCNet Research Center, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · General and Pancreatic Surgery, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. Electronic address: roberto.salvia@univr.it. ·Surgery · Pubmed #29454468.

ABSTRACT: BACKGROUND: Mural nodules (MNs) have a predominant role in the 2016 revision of the international guidelines on intraductal papillary mucinous neoplasms (IPMN) of the pancreas. The aim of this study was to evaluate MNs as predictors of invasive cancer (iCa) or high-grade dysplasia (HGD) in IPMNs and to investigate the role of MN size in risk prediction. METHODS: A PRISMA-compliant systematic review of the literature and meta-analysis on selected studies were conducted. The random effect model was adopted, and the pooled SMD (standardized mean difference) obtained. The surgical series of IPMNs at a single high-volume institution was reviewed. RESULTS: This review included 70 studies and 2297 resected IPMNs. MNs have a positive predictive value for malignancy of 62.2%. The meta-analysis suggested that MN size has a considerable effect on predicting IPMNs with both iCa or HGD with a mean SMD of 0.79. All studies included in the meta-analysis used contrast-enhanced endosonography (CE-EUS) to assess MNs. Due to the heterogeneity of the proposed thresholds, no reliable MN size cut-off was identified. Of 317 IPMNs resected at our institution, 102 (32.1%) had a preoperative diagnosis of MN. Multivariate analysis showed that MN is the only independent predictor of iCa and HGD for all types of IPMNs. CONCLUSION: MNs are reliable predictors of iCa and HGD in IPMNs as proposed by the 2016 IAP guidelines. CE-EUS seems to be the best tool for characterizing size and has the best accuracy for predicting malignancy. Further studies should determine potential MN dimensional cut-offs.

7 Review Increased incidence of extrapancreatic neoplasms in patients with IPMN: Fact or fiction? A critical systematic review. 2015

Pugliese, Luigi / Keskin, Muharrem / Maisonneuve, Patrick / D'Haese, Jan G / Marchegiani, Giovanni / Wenzel, Patrick / Del Chiaro, Marco / Ceyhan, Güralp O. ·Unit of General Surgery 2, Department of Surgery, IRCCS Policlinico San Matteo, Pavia, Italy. · Division of Gastroenterology, Department of Internal Medicine, Ege University, Izmir, Turkey. · Division of Epidemiology and Statistics, European Institute of Oncology, Milan, Italy. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Department of Surgery, Pancreas Institute, Verona University Hospital, Verona, Italy. · Department of Gastroenterology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. · Division of Surgery, CLINTEC, Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. Electronic address: gueralp.ceyhan@tum.de. ·Pancreatology · Pubmed #25841270.

ABSTRACT: BACKGROUND: To identify potential associations between intraductal papillary mucinous neoplasm of the pancreas (IPMN) and extrapancreatic neoplasms (EPN), a systematic review of the literature has been performed. METHODS: A systematic search of Medline/Pubmed was performed according to the PRISMA guidelines for reporting systematic reviews and meta-analysis for the following search terms: "extrapancreatic", "non pancreatic", "additional pancreatic", "additional primary" and alternatively matched with "neoplasms/tumours/cancers/malignancies/lesions". The results obtained specifically for IPMN were examined one by one by two independent investigators for further data selection and extraction. RESULTS: Fifteen studies were identified to be suitable and included for systematic review. Fourteen reported an elevated risk for extrapancreatic malignancy, particularly gastric and colon cancer, while the largest and only prospective study did not find any association. Most studies were retrospective with a weak level of evidence that was not substantially enhanced even by a recent multicentre case series. CONCLUSIONS: The available data on this clinically relevant question remain inconclusive. Due to lacking evidence on extrapancreatic neoplasms in IPMN patients, only a standard surveillance can be advised.

8 Review Is it safe to follow side branch IPMNs? 2014

Marchegiani, Giovanni / Fernández-del Castillo, Carlos. · ·Adv Surg · Pubmed #25293604.

ABSTRACT: Management of Bd-IPMN remains challenging. Critical appraisal of the published literature reveals that the actual treatment of what is presumed to be Bd-IPMN remains unsatisfactory, with a high rate of surgically overtreated patients. Until we accrue more precise knowledge of the natural history of Bd-IPMN, management of patients with this presumed diagnosis should be individually tailored and preferably carried out in centers with a high expertise. For now, the authors strongly think that the old guidelines should be followed in most patients because these have proven to correctly identify lesions that can be safely followed. Although the new guidelines allow for follow-up of lesions greater than 3 cm, and for the most part this is safe, they should be used cautiously in younger patients because very close surveillance would be required for their long remaining lifespan.

9 Review Pancreatic hepatoid carcinoma: a review of the literature. 2013

Marchegiani, Giovanni / Gareer, Haytham / Parisi, Alice / Capelli, Paola / Bassi, Claudio / Salvia, Roberto. ·Department of Surgery, Verona University Hospital, Verona, Italy. ·Dig Surg · Pubmed #24281319.

ABSTRACT: BACKGROUND: Hepatoid carcinomas (HCs) are extrahepatic neoplasms exhibiting features of hepatocellular tumors in terms of morphology and immunohistochemistry. They have been described in several organs, most notably in the stomach and ovary. They can present in pure forms or in association with other morphological aspects, such as endocrine tumors or ductal adenocarcinomas. The aim of this review is to describe aspects of hepatoid adenocarcinoma of the pancreas with regard to epidemiology, diagnosis, and treatment. METHODS: The PubMed database was searched for publications addressing hepatoid adenocarcinoma of the pancreas. We have searched for articles including the following keywords: 'pancreatic hepatoid carcinoma', 'ectopic liver cancer' and 'rare pancreas neoplasm' published to date. As references, we used case reports and review articles. RESULTS: Pancreatic forms of HCs are extremely uncommon: only 22 cases have been reported. CONCLUSIONS: The possibility of an HC of the pancreas should be considered in the differential diagnosis of an uncommon pathological mass of the pancreas. Treatment seems to be related to the association with other neoplasms, tumor extension at the time of diagnosis and the possibility to perform a radical resection. The common embryologic origin of the pancreas and liver, together with peculiar environmental factors, may explain the development of pancreatic HCs.

10 Review Drain management after pancreatic resection: state of the art. 2011

Giovinazzo, Francesco / Butturini, Giovanni / Salvia, Roberto / Mascetta, Giuseppe / Monsellato, Daniela / Marchegiani, Giovanni / Pederzoli, Paolo / Bassi, Claudio. ·Surgical Department, Pancreas Centre, Hospital of 'G.B.Rossi', University of Verona, Piazzale 'L.A. Scuro', 37134, Verona, Italy. · Surgical Department, Pancreas Centre, Hospital of 'G.B.Rossi', University of Verona, Piazzale 'L.A. Scuro', 37134, Verona, Italy. claudio.bassi@univr.it. · Department of Surgery, General Surgery B, P.Le L.A. Scuro 10, 37134, Verona, Italy. claudio.bassi@univr.it. ·J Hepatobiliary Pancreat Sci · Pubmed #21861143.

ABSTRACT: BACKGROUND: Placement of intraperitoneal drain (ID) after abdominal surgery is a common practice. Postoperative pancreatic fistula (POPF), incidence of which ranges from 2% to more than 30%, represents the most common major complication after pancreatic resection. The goal of this paper is to review the state of the art in ID management after pancreatic resection. METHODS: Data from randomized controlled trials (RCT) are reported together with data from our institution in the period before and after the start of the two reported RCTs. RESULTS: One thousand five hundred eighty patients underwent surgical resection for pancreatic lesions at our institution from 1990 to 2010. The overall rate of POPF was 23% before and 19.5% after (p = 0.24) the performance of the RCTs. Both postoperative morbidity and average in-hospital stay were higher in the period before the RCTs (13.6 ± 11.4 versus 13.4 ± 10.3 days, respectively). CONCLUSIONS: POPF is a complex and multifactorial complication after pancreatic surgery. On the basis of the present results and review of the RCTs, the value of ID and its management after pancreatic surgery remain unclear.

11 Review Pancreaticoduodenectomy for pancreatic cancer: the Verona experience. 2011

Malleo, Giuseppe / Marchegiani, Giovanni / Salvia, Roberto / Butturini, Giovanni / Pederzoli, Paolo / Bassi, Claudio. ·Department of Surgery, General Surgery B, G.B. Rossi Hospital, P.Le L.A. Scuro 10, 37134, Verona, Italy. ·Surg Today · Pubmed #21431477.

ABSTRACT: Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related mortality in the Western world. The current treatment is multimodal, and in resectable patients radical surgery represents the key-step toward long-term survival. Pancreaticoduodenectomy (PD) is the most widely performed operation, because the majority of ductal carcinomas arise in the head of the pancreas. Once considered extremely hazardous, PD has evolved into a safe procedure, with mortality below 5% and morbidity rates in the range from 20% to 60% at high-volume centers. Verona is regarded as one of the most prominent institutions for pancreatic surgery in Europe. More than 5500 patients with pancreatic diseases have been managed, and the surgical case load has increased substantially, with more than 1350 PDs performed. This review discusses this center's experience in surgical treatment of pancreatic head cancer. Furthermore, the preliminary results of radiofrequency thermal ablation of locally advanced ductal cancer are presented.

12 Clinical Trial Is there a role for near-infrared technology in laparoscopic resection of pancreatic neuroendocrine tumors? Results of the COLPAN "colour-and-resect the pancreas" study. 2017

Paiella, Salvatore / De Pastena, Matteo / Landoni, Luca / Esposito, Alessandro / Casetti, Luca / Miotto, Marco / Ramera, Marco / Salvia, Roberto / Secchettin, Erica / Bonamini, Deborah / Manzini, Gessica / D'Onofrio, Mirko / Marchegiani, Giovanni / Bassi, Claudio. ·General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. salvatore.paiella@univr.it. · General and Pancreatic Surgery Department, Pancreas Institute, University and Hospital Trust of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. · Radiology Department, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. ·Surg Endosc · Pubmed #28374260.

ABSTRACT: BACKGROUND: The intraoperative identification of pancreatic neuroendocrine tumors (PanNETs) is of utmost importance to drive their laparoscopic resection. Near-infrared (NIR) surgery has emerged as a new technique for localizing tumors or neoplastic tissue. This study aimed to explore the results of the application of NIR in the laparoscopic resection of PanNETs. METHODS: Per protocol we enrolled ten subjects undergoing laparoscopic pancreatic surgery for PanNET from March 2016 to October 2016. During surgery, the patients were injected with indocyanine green dye (ICG, 25 mg given in 5 boli of 5 mg each). The switch-activation of NIR was performed to identify PanNETs. An ex-post analysis of the images was realized using ImageJ Software® to calculate the fluorescence signal. RESULTS: NIR imaging identified all ten PanNETs. Nine (90%) laparoscopic distal pancreatectomy with splenectomy and one (10%) laparoscopic enucleation were performed. The mean maximum tumor dimension was 2.4 cm (range 1-4 cm). Eight non-functioning PanNETs (80%) and two insulinomas (20%) were found at the final pathology. Nine out of ten (90%) PanNETs were detected after the second ICG bolus. The mean latency time was 80 s and the mean visibility time was 220 s. The peak of tumor visualization was reached 20 min after the last bolus. This finding was confirmed by the ex-post analysis of the fluorescence signal (mean signal-to-background ratio of 7.7, p = 0.001). NIR identified two additional lesions, which turned out to be normal lymph nodes at final pathology. A fluorescent signal was identified at the bed of the enucleation, and thus, a further exeresis was performed and final pathology revealed that is was residual neoplastic tissue. CONCLUSIONS: This explorative study shows that NIR with ICG can have a role in laparoscopic pancreatic resection of PanNETs. Further studies are needed to assess the proper setting and role of this new and promising technology.

13 Clinical Trial The proteome of postsurgical pancreatic juice. 2015

Marchegiani, Giovanni / Paulo, Joao A / Sahora, Klaus / Fernández-Del Castillo, Carlos. ·From the *Department of Surgery, Massachusetts General Hospital, Harvard Medical School; and †Department of Cell Biology, Harvard Medical School, Boston, MA. ·Pancreas · Pubmed #25875796.

ABSTRACT: OBJECTIVE: This study aimed to evaluate the proteome of the pancreatic juice after pancreatectomy. METHODS: Pancreatic juice samples were obtained during surgery and the postoperative period. Proteins were identified by mass spectrometry-based protein quantification technology and compared with published data of the nonoperated pancreas. Subgroup analyses were done in patients with pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant chemotherapy and in smokers. RESULTS: Five hundred eighteen proteins were identified in the postoperative pancreatic juice, encompassing all of the main organ functions. Sixty-seven of these were also present in the published data of the nonoperated pancreas and 7 of these had significant variation of concentration after surgery. Growth factors that have been described in postsurgical regeneration of the liver were not found to be overexpressed, whereas clusterin did, confirming the finding of previous experimental studies on pancreatic regeneration. Several proteins involved in immunomodulation and organ functions were differently expressed, depending on PDAC, neoadjuvant therapy, and smoking. CONCLUSIONS: The proteome of the pancreas after surgical resection contains factors related to all main organ functions, changes over time, and is different in patients with PDAC receiving neoadjuvant therapy and in smokers. The pancreas reacts to the surgical trauma by producing proteins that protect the organ and stimulate the restoration of its function.

14 Article Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma. 2020

Strijker, Marin / Soer, Eline C / de Pastena, Matteo / Creemers, Aafke / Balduzzi, Alberto / Beagan, Jamie J / Busch, Olivier R / van Delden, Otto M / Halfwerk, Hans / van Hooft, Jeanin E / van Lienden, Krijn P / Marchegiani, Giovanni / Meijer, Sybren L / van Noesel, Carel J / Reinten, Roy J / Roos, Eva / Schokker, Sandor / Verheij, Joanne / van de Vijver, Marc J / Waasdorp, Cynthia / Wilmink, Johanna W / Ylstra, Bauke / Besselink, Marc G / Bijlsma, Maarten F / Dijk, Frederike / van Laarhoven, Hanneke W. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, Amsterdam, The Netherlands. · Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Department of Gastroenterology and Hepatology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. · Oncode Institute, Amsterdam, The Netherlands. ·Int J Cancer · Pubmed #31340061.

ABSTRACT: Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow-up in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantiated, especially in mPDAC. In this retrospective analysis of prospectively collected samples, cell-free DNA from plasma samples of 58 treatment-naive mPDAC patients was isolated and sequenced using a custom-made pancreatobiliary NGS panel. Pathogenic mutations were detected in 26/58 (44.8%) samples. Cross-check with droplet digital PCR showed good agreement in Bland-Altman analysis (p = 0.217, nonsignificance indicating good agreement). In patients with liver metastases, ctDNA was more frequently detected (24/37, p < 0.001). Tumor volume (3D reconstructions from imaging) and ctDNA variant allele frequency (VAF) were correlated (Spearman's ρ = 0.544, p < 0.001). Median overall survival (OS) was 3.2 (95% confidence interval [CI] 1.6-4.9) versus 8.4 (95% CI 1.6-15.1) months in patients with detectable versus undetectable ctDNA (p = 0.005). Both ctDNA VAF and tumor volume independently predicted OS after adjustment for carbohydrate antigen 19.9 and treatment regimen (hazard ratio [HR] 1.05, 95% CI 1.01-1.09, p = 0.005; HR 1.00, 95% CI 1.01-1.05, p = 0.003). In conclusion, our study showed that ctDNA detection rates are higher in patients with larger tumor volume and liver metastases. Nevertheless, measurements may diverge and, thus, can provide complementary information. Both ctDNA VAF and tumor volume were strong predictors of OS.

15 Article International validation and update of the Amsterdam model for prediction of survival after pancreatoduodenectomy for pancreatic cancer. 2019

van Roessel, Stijn / Strijker, Marin / Steyerberg, Ewout W / Groen, Jesse V / Mieog, J Sven / Groot, Vincent P / He, Jin / De Pastena, Matteo / Marchegiani, Giovanni / Bassi, Claudio / Suhool, Amal / Jang, Jin-Young / Busch, Olivier R / Halimi, Asif / Zarantonello, Laura / Groot Koerkamp, Bas / Samra, Jaswinder S / Mittal, Anubhav / Gill, Anthony J / Bolm, Louisa / van Eijck, Casper H / Abu Hilal, Mohammed / Del Chiaro, Marco / Keck, Tobias / Alseidi, Adnan / Wolfgang, Christopher L / Malleo, Giuseppe / Besselink, Marc G. ·Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. · Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands. · Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK. · Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. · Pancreatic Surgery Unit, Division of Surgery, Karolinska Institute at Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden. · Department of Surgery, Erasmus Medical Center, Erasmus University Rotterdam, Rotterdam, the Netherlands. · Department of Surgery, Royal North Shore Hospital, St Leonards, University of Sydney, Sydney, NSW, Australia. · Cancer Diagnosis and Pathology Group Kolling Institute of Medical Research and University of Sydney, Sydney, NSW, Australia. · Department of Surgery, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany. · Division of Surgical Oncology, Department of Surgery, University of Colorado at Denver-Anschutz Medical Campus, Aurora, CO, USA. · Section of Hepato-Pancreato-Biliary & Endocrine Surgery, Virginia Mason Medical Center, Seattle, WA, USA. · Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address: m.g.besselink@amsterdamumc.nl. ·Eur J Surg Oncol · Pubmed #31924432.

ABSTRACT: BACKGROUND: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer. METHODS: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement. RESULTS: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3-year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001). CONCLUSIONS: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www.pancreascalculator.com may facilitate use in daily practice and future trials.

16 Article Solid Pseudopapillary Neoplasms of the Pancreas: Clinicopathologic and Radiologic Features According to Size. 2019

De Robertis, Riccardo / Marchegiani, Giovanni / Catania, Matteo / Ambrosetti, Maria Chiara / Capelli, Paola / Salvia, Roberto / D'Onofrio, Mirko. ·Department of Radiology, Azienda Ospedaliera Universitaria Integrata Verona, Piazzale A. Stefani 1, 37126 Verona, Italy. · Department of Pancreatic Surgery, G. B. Rossi Hospital, University of Verona, Verona, Italy. · Department of Radiology, G. B. Rossi Hospital, University of Verona, Verona, Italy. · Department of Pathology, G. B. Rossi Hospital, University of Verona, Verona, Italy. ·AJR Am J Roentgenol · Pubmed #31310181.

ABSTRACT:

17 Article Residual pancreatic function after pancreaticoduodenectomy is better preserved with pancreaticojejunostomy than pancreaticogastrostomy: A long-term analysis. 2019

Benini, Luigi / Gabbrielli, Armando / Cristofori, Chiara / Amodio, Antonio / Butturini, Giovanni / Cardobi, Nicolò / Sozzi, Carlo / Frulloni, Luca / Mucelli, Roberto Pozzi / Crinò, Stefano / Bassi, Claudio / Marchegiani, Giovanni / Andrianello, Stefano / Malleo, Giuseppe / Salvia, Roberto. ·Gastroenterology B, Department of Medicine, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Radiology, Department of Diagnosis and of Pathology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. Electronic address: claudio.bassi@univr.it. ·Pancreatology · Pubmed #31005377.

ABSTRACT: BACKGROUND: Pancreatico-enteric anastomosis after pancreaticoduodenectomy can be performed using either a pancreaticojejunostomy (PJ) or pancreaticogastrostomy (PG). Differences in surgical outcomes are still a matter of debate, and less is known about long-term functional outcomes. METHODS: Twelve years after the conclusion of a comparative study evaluating the surgical outcomes of PJ and PG (Bassi et al., Ann Surg 2005), available patients underwent morphological and functional pancreatic assessment: pancreatic volume and duct diameter measured by MRI, impaired secretion after secretin, fecal fat, fecal elastase-1 (FE-1), serum vitamin D and endocrine function. Quality of life and symptom scores were evaluated with the EORTC QLQ-C30 questionnaire. RESULTS: Only 34 patients were available for assessment. No differences were found in terms of BMI variation, endocrine function, quality of life or symptoms. Exocrine function was more severely impaired after PG than after PJ (fecal fats 26.6 ± 4.1 vs 18.2 ± 3.6 g/day; FE-1 121.4 ± 6.7 vs 170.2 ± 25.5 μg/g, vitamin D 18.1 ± 1.8 vs. 23.2 ± 3.1 ng/mL). MRI assessment identified a lower pancreatic volume (26 ± 3.1 vs. 36 ± 4.1 cm CONCLUSION: Compared to PJ, PG is associated with a more severely impaired exocrine function long-term, but they result similar endocrine function and quality of life. In patients with a long life expectancy, this should be taken into account.

18 Article Reinforced stapler versus ultrasonic dissector for pancreatic transection and stump closure for distal pancreatectomy: A propensity matched analysis. 2019

Pulvirenti, Alessandra / Landoni, Luca / Borin, Alex / De Pastena, Matteo / Fontana, Martina / Pea, Antonio / Esposito, Alessandro / Casetti, Luca / Tuveri, Massimiliano / Paiella, Salvatore / Marchegiani, Giovanni / Malleo, Giuseppe / Salvia, Roberto / Bassi, Claudio. ·Unit of General and Pancreatic Surgery, University of Verona Hospital Trust, Italy. · Unit of General and Pancreatic Surgery, University of Verona Hospital Trust, Italy. Electronic address: Roberto.salvia@univr.it. ·Surgery · Pubmed #30975498.

ABSTRACT: BACKGROUND: Postoperative pancreatic fistula is the primary contributor to morbidity after distal pancreatectomy. To date, no techniques used for the transection and closure of the pancreatic stump have shown clear superiority over the others. This study aimed to compare the rate of postoperative pancreatic fistula after pancreatic transection conducted with a reinforced stapler versus an ultrasonic dissector after a distal pancreatectomy. METHOD: Prospectively collected data of consecutive patients who underwent distal pancreatectomy from 2014 to 2017 were reviewed retrospectively. We included distal pancreatectomies in which pancreatic transection was performed by reinforced stapler or ultrasonic dissector; we excluded extended distal pancreatectomies. To overcome the absence of randomization, we conducted a propensity matching analysis according to risk factors for postoperative pancreatic fistula. RESULTS: Overall, 200 patients met the inclusion criteria. The reinforced stapler was employed in 108 patients and the ultrasonic dissector in 92 cases. After one-to-one propensity matching, 92 patients were selected from each group. The matched reinforced stapler and ultrasonic dissector cohort had no differences in baselines characteristics except for the mini-invasive approach, which was more common in the ultrasonic dissector group (34% vs 51%, P = .025). Overall, 48 patients (26%) developed a postoperative pancreatic fistula, 46 (25%) a grade B postoperative pancreatic fistula, and 2 (1%) a grade C postoperative pancreatic fistula. In the reinforced stapler group, the rate of postoperative pancreatic fistula was 12% (n = 11) and in the ultrasonic dissector group 40% (n = 37) with a P < .001. CONCLUSION: The results of this study suggest that the use of reinforced stapler for pancreatic transection decreases the risk of postoperative pancreatic fistula. A randomized trial is required to confirm these preliminary data.

19 Article Preoperative Imaging Evaluation after Downstaging of Pancreatic Ductal Adenocarcinoma: A Multi-Center Study. 2019

Beleù, Alessandro / Calabrese, Angela / Rizzo, Giulio / Capelli, Paola / Bellini, Nicolò / Caloggero, Simona / Calbi, Roberto / Tinazzi Martini, Paolo / De Robertis, Riccardo / Carbognin, Giovanni / Marchegiani, Giovanni / Scarpa, Aldo / Salvia, Roberto / Bassi, Claudio / D'Onofrio, Mirko. ·Department of Radiology, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. ale.beleu@gmail.com. · Department of Radiology, Istituto Oncologico Giovanni Paolo II, 70124 Bari, Italy. acalabrese22@gmail.com. · Department of Radiology, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. giulioriz11@gmail.com. · Department of Pathology, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. paolacapelli@hotmail.com. · Department of Radiology, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. bellini.nico@live.it. · Department of Radiology, G. Martino Hospital, University of Messina, 98125 Messina, Italy. simona.caloggero@hotmail.it. · Department of Radiology, Ospedale Generale Regionale "F. Miulli", 70021 Acquaviva della Fonti, Italy. calbi.roberto@gmail.com. · Department of Radiology, Ospedale P. Pederzoli, 37019 Peschiera del Garda, Italy. paolo.tinazzimartini@univr.it. · Department of Radiology, Ospedale Civile Maggiore Borgo Trento, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy. riccardo.derobertislombardi@univr.it. · Department of Radiology, Ospedale "Sacro Cuore, Don Calabria", 37024 Negrar, Italy. giovanni.carbogni@univr.it. · Department of Surgery, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. giovanni.marchegiani@aovr.veneto.it. · Department of Pathology, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. aldo.scarpa@univr.it. · Department of Surgery, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. roberto.salvia@univr.it. · Department of Surgery, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. claudio.bassi@univr.it. · Department of Radiology, G.B. Rossi Hospital, University of Verona, 37134 Verona, Italy. mirko.donofrio@univr.it. ·Cancers (Basel) · Pubmed #30823544.

ABSTRACT: INTRODUCTION: Evaluation of pancreatic ductal adenocarcinoma (PDAC) after chemoradiotherapy downstaging is challenging due to computed tomography (CT) overestimation of tumor extension and residual vascular involvement, limiting access to surgery to some patients with potentially resectable tumors. With this study, we wanted to assess which radiological findings are most reliable at pre-operative imaging in the evaluation of PDAC after chemoradiotherapy in order to achieve complete resection. METHODS: We retrospectively enrolled 71 patients with locally advanced and borderline resectable PDAC who underwent neoadjuvant chemoradiotherapy. Pre-operative CT or magnetic resonance (MR) have been evaluated by three radiologists to assess major qualitative and quantitative parameters of lesions. Accuracy, sensitivity, and specificity compared to anatomopathological results were evaluated for each parameter. Cohen's K-coefficient has been calculated to evaluate the inter-observer agreement (IOA). Both single and consensus lecture have been tested. Different dimensional cut-offs were tested to categorize tumors according to their major axis and to compare with anatomopathological diameter, tumor persistence, and margin infiltration. RESULTS: A 25 mm cut-off was 67% sensitive, 90% specific, and 77% accurate in assessing real tumor dimension. 25 mm cut-off reported a 64% sensitivity, 78% specificity, and 69% accuracy in assessing R0 resection. Each 5 mm increment of major axis dimension there is an odds ratio (OR) 1.79 (95% CI 1.13⁻2.80, CONCLUSION: Imaging methods tend to underestimate PDAC resectability after neoadjuvant-CRT. IOA is poor to fair in evaluating most of the qualitative parameters of downstaged pancreatic adenocarcinoma. Surgery should be considered for downstaged borderline resectable PDACs, independently from perivascular cuff presence, especially for tumors smaller than 25 mm.

20 Article Dislocation of intra-abdominal drains after pancreatic surgery: results of a prospective observational study. 2019

Marchegiani, Giovanni / Ramera, Marco / Viviani, Elena / Lombardo, Fabio / Cybulski, Adam / Chincarini, Marco / Malleo, Giuseppe / Bassi, Claudio / Zamboni, Giulia A / Salvia, Roberto. ·Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of Radiology, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Department of General and Pancreatic Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. claudio.bassi@univr.it. · Department of General and Pancreatic Surgery, "GB Rossi" Hospital, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. claudio.bassi@univr.it. ·Langenbecks Arch Surg · Pubmed #30771076.

ABSTRACT: PURPOSE: The use of intra-abdominal drains after major surgical procedures represents a well-established but controversial practice. No data are available regarding both the occurrence and the potential impact of their postoperative accidental dislocation. The aim of this study is to assess the actual rate of dislocation of intra-abdominal drains postoperatively and to evaluate its clinical impact. METHODS: This is a prospective observational study using major pancreatic surgery as a model. Ninety-one consecutive patients undergoing pancreatoduodenectomy (PD) or distal pancreatectomy (DP) underwent low-dose, non-enhanced computed tomography (LDCT) on postoperative days (POD) 1 and 3 in a blinded fashion to assess the position of drains. We compared the outcomes of patients with dislocated and correctly placed drains. RESULTS: Overall, drains were dislocated in 30 patients (33%), without differences between PD and DP. Most of dislocations were already present on POD 1 (77%). Postoperative complications occurred in 57% of patients, and the rate of postoperative pancreatic fistula (POPF) was 27%. The dislocated cohort had lesser morbidity (40% vs. 66%; relative risk (RR), 0.35; 95% CI, 0.14-0.86; P = 0.020), and the rate of POPF (3% vs. 39%, respectively; RR, 0.05; 95% CI, 0.01-0.42; P < 0.001). After PD, patients with dislocated drains had a shorter hospital stay (12 vs. 20 days; P = 0.015). No significant differences in terms of need for percutaneous drainage procedures, abdominal collections, or grade C POPFs were found between the groups. CONCLUSIONS: Dislocation of intra-abdominal drains is an early and frequent event after major pancreatic resection. Its occurrence might protect against the negative effects of maintaining drainage, eventually leading to better postoperative outcomes. This data reinforces the knowledge that surgical drains might be detrimental in selected cases.

21 Article Correlation between appearance of the retroportal fat plane at preoperative CT and pathology findings in resected adenocarcinoma of the pancreatic head. 2019

Lombardo, F / Zamboni, G A / Bonatti, M / Chincarini, M / Ambrosetti, M C / Marchegiani, G / Malleo, G / Mansueto, G / Pozzi Mucelli, R. ·Department of Radiology, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. Electronic address: fabio.lombardo@me.com. · Department of Radiology, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. · Department of Radiology, Ospedale Centrale di Bolzano, Via L. Boehler 5, 39100 Bolzano, Italy. · Department of Surgery, University of Verona, Piazzale L.A. Scuro 10, 37134, Verona, Italy. ·Clin Radiol · Pubmed #30691733.

ABSTRACT: AIM: To correlate the appearance of the retroportal fat plane at preoperative computed tomography (CT) and the pathology findings in resected adenocarcinoma of the pancreatic head (PDAC). MATERIAL AND METHODS: Forty-eight patients with resected PDAC of the pancreatic head were included (24 men, 24 women, mean age 63 years, median BMI 24.1). All patients underwent CT <30 days before surgery. The state of the retroperitoneal resection margin and the presence of lymphatic or perineural invasion were obtained from pathology reports. CT images were reviewed independently by two radiologists for assessment of the retroportal fat plane and graded in two categories (clear/effaced). Inter-reader discrepancies were solved in consensus. Interobserver agreement was calculated and Fisher's test was used to assess the correlation between CT and pathology findings. Visceral fat areas were measured and correlated with CT findings. RESULTS: A clear retroportal fat plane was significantly associated with a negative retroperitoneal margin at pathology with 100% specificity and PPV (p=0.0001). No association was observed between the appearance of the fat plane at CT and the presence of lymphatic or perineural invasion (p=ns). Interobserver agreement for retroportal fat plane evaluation was good (0.741). False-positive cases had a significantly lower visceral fat area than the correctly classified patients (p=0.0480). CONCLUSIONS: A clear retroportal fat plane is significantly associated with negative retroperitoneal resection margins at pathology. The lack of visceral adipose tissue can lead to overestimation of retroportal fat plane involvement at preoperative CT.

22 Article The Actual Prevalence of Symptoms in Pancreatic Cystic Neoplasms: A Prospective Propensity Matched Cohort Analysis. 2019

Marchegiani, Giovanni / Andrianello, Stefano / Miatello, Chiara / Pollini, Tommaso / Secchettin, Erica / Tedesco, Giorgia / D'Onofrio, Mirko / Malleo, Giuseppe / Bassi, Claudio / Salvia, Roberto. ·Department of General and Pancreatic Surgery, 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 General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy, roberto.salvia@univr.it. ·Dig Surg · Pubmed #30541002.

ABSTRACT: BACKGROUND: The prevalence of symptoms in pancreatic cystic neoplasms (PCNs) is mainly based on retrospective surgical series. The aim of this study is to describe the actual prevalence of symptoms in PCNs under surveillance. METHODS: Patients with PCNs under surveillance observed from 2015 to 2017 were submitted to magnetic resonance imaging (MRI) and a specific interview. An identical survey was carried out on a control population matched for age, sex, and comorbidities in which any pancreatic disease was excluded by MRI. RESULTS: Two groups of 184 individuals were compared. Patients with PCNs have a similar prevalence of abdominal pain when compared to controls (35.2 vs. 28.8, p = 0.2). PCNs in the distal pancreas experienced a significantly increased prevalence of abdominal pain (42.3 vs. 28.8%, p = 0.04), whereas size and presumed connection with the ductal system did not affect the prevalence of abdominal pain. PCNs associated with abdominal pain did not differ in terms of clinical and radiological features from asymptomatic ones. CONCLUSION: Patients with PCNs under surveillance have a similar prevalence of abdominal pain when compared to a matched population of controls. Abdominal pain might not correlate with radiological signs of malignancy.

23 Article Patterns of Recurrence after Resection for Pancreatic Neuroendocrine Tumors: Who, When, and Where? 2019

Marchegiani, Giovanni / Landoni, Luca / Andrianello, Stefano / Masini, Gaia / Cingarlini, Sara / D'Onofrio, Mirko / De Robertis, Riccardo / Davì, Mariavittoria / Capelli, Paola / Manfrin, Erminia / Amodio, Antonio / Paiella, Salvatore / Malleo, Giuseppe / Damoli, Isacco / Miotto, Marco / Bianchi, Beatrice / Nessi, Chiara / Vivani, Elena / Scarpa, Aldo / Salvia, Roberto / Bassi, Claudio. ·Department of General and Pancreatic Surgery, 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 Medicine, University of Verona Hospital Trust, Verona, Italy. · Pathology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of Gastroenterology, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy. · Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy, roberto.salvia@univr.it. ·Neuroendocrinology · Pubmed #30481765.

ABSTRACT: BACKGROUND/AIMS: Pancreatic neuroendocrine tumors (pan-NENs) represent an increasingly common indication for pancreatic resection, but there are few data regarding possible recurrence after surgery. The aim of the study was to describe the frequency, timing, and patterns of recurrence after resection for pan-NENs with consequent implications for postoperative follow-up. METHODS: We performed a retrospective analysis of pan-NENs resected between 1990 and 2015 at The Pancreas Institute, University of Verona Hospital Trust. Predictors of recurrence were assessed. Survival analysis was conducted using the Kaplan-Meier and conditional survival (CS) methods. RESULTS: The cohort consisted of 487 patients with a median follow-up of 71 months. Recurrence developed in 12.3%: 54 (11.1%) liver metastases, 11 (2.3%) local recurrence, 10 (2.1%) nodal recurrence, and 8 (1.6%) metastases in other organs. Thirty-one (6.4%) died due to disease recurrence. Size > 21 mm, G3 grade, nodal metastasis, and vascular infiltration were independent predictors of overall recurrence. Recurrence occurred either during the first year of follow-up (n = 9), or after 10 years (n = 4). CS analysis revealed that nonfunctioning G1 pan-NEN ≤20 mm without nodal metastasis or vascular invasion had a negligible risk of developing recurrence. In the present series, after 5 years of follow-up without developing recurrence, tumor recurrence occurred only in the form of liver metastases. CONCLUSIONS: Recurrence of pan-NENs is rare and is predicted by tumor size, nodal metastasis, grading, and vascular invasion. Patients with G1 pan-NEN without nodal metastasis and vascular invasion may be considered cured by surgery. After 5 years without recurrence, follow-up should focus on excluding the development of liver metastases.

24 Article Molecular alterations associated with metastases of solid pseudopapillary neoplasms of the pancreas. 2019

Amato, Eliana / Mafficini, Andrea / Hirabayashi, Kenichi / Lawlor, Rita T / Fassan, Matteo / Vicentini, Caterina / Barbi, Stefano / Delfino, Pietro / Sikora, Katarzyna / Rusev, Borislav / Simbolo, Michele / Esposito, Irene / Antonello, Davide / Pea, Antonio / Sereni, Elisabetta / Ballotta, Maria / Maggino, Laura / Marchegiani, Giovanni / Ohike, Nobuyuki / Wood, Laura D / Salvia, Roberto / Klöppel, Günter / Zamboni, Giuseppe / Scarpa, Aldo / Corbo, Vincenzo. ·ARC-Net Research Centre, University and Hospital Trust of Verona, Verona, Italy. · Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy. · Department of Pathology, Tokai University School of Medicine, Isehara, Japan. · Institute of Pathology, Heinrich-Heine-University and University Hospital of Düsseldorf, Düsseldorf, Germany. · Department of Surgery, General Surgery B, University of Verona, Verona, Italy. · Section of Anatomic Pathology, Azienda Ospedaliera Rovigo, Rovigo, Italy. · Department of Pathology and Laboratory Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Pathology, Technical University Munich, Munich, Germany. · Division of Pathology, Sacro Cuore-Don Calabria Hospital, Negrar, Italy. ·J Pathol · Pubmed #30306561.

ABSTRACT: Solid pseudopapillary neoplasms (SPN) of the pancreas are rare, low-grade malignant neoplasms that metastasise to the liver or peritoneum in 10-15% of cases. They almost invariably present somatic activating mutations of CTNNB1. No comprehensive molecular characterisation of metastatic disease has been conducted to date. We performed whole-exome sequencing and copy-number variation (CNV) analysis of 10 primary SPN and comparative sequencing of five matched primary/metastatic tumour specimens by high-coverage targeted sequencing of 409 genes. In addition to CTNNB1-activating mutations, we found inactivating mutations of epigenetic regulators (KDM6A, TET1, BAP1) associated with metastatic disease. Most of these alterations were shared between primary and metastatic lesions, suggesting that they occurred before dissemination. Differently from mutations, the majority of CNVs were not shared among lesions from the same patients and affected genes involved in metabolic and pro-proliferative pathways. Immunostaining of 27 SPNs showed that loss or reduction of KDM6A and BAP1 expression was significantly enriched in metastatic SPNs. Consistent with an increased transcriptional response to hypoxia in pancreatic adenocarcinomas bearing KDM6A inactivation, we showed that mutation or reduced KDM6A expression in SPNs is associated with increased expression of the HIF1α-regulated protein GLUT1 at both primary and metastatic sites. Our results suggest that BAP1 and KDM6A function is a barrier to the development of metastasis in a subset of SPNs, which might open novel avenues for the treatment of this disease. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

25 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.

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