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Courtel T, Orbach D, Lacour B, Roumy M, Hescot S, Desandes E, Philippe-Chomette P, Sarnacki S, Irtan S, Dijoud F, Kubicek P, Brisse H, Fresneau B, Pire A, Réguerre Y, Mallebranche C. Childhood pancreatic neuroendocrine neoplasms: A national experience. Pediatr Blood Cancer 2025; 72:e31258. [PMID: 39135330 DOI: 10.1002/pbc.31258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 07/23/2024] [Accepted: 07/26/2024] [Indexed: 12/24/2024]
Abstract
Pancreatic neuroendocrine neoplasms (pNENs) diagnosed in childhood are very rare, with few data available. The aim was to describe the clinical presentation and behavior of children with pNENs at a national level. METHODS National multicenter retrospective study of all patients, aged from 0 to 17 years at diagnosis, treated from 2011 to 2020 for a pNEN and registered in the French National Registry of Childhood Cancers or FRACTURE database. RESULTS Fifteen patients, 13 well-differentiated pancreatic neuroendocrine tumors (pNETs) and two neuroendocrine carcinomas (pNECs), were selected. Median age at diagnosis was 14 years (range, 7-17). Eight patients, all with localized disease, had a cancer predisposition syndrome (CPS), including five cases diagnosed during systematic screening. Five (31%) had metastatic disease at diagnosis: three grade 2 pNETs and two pNECs. First line therapy included exclusive pancreatectomy (seven cases, all M0), active surveillance (three cases, all M0), medical therapies (somatostatin analogues, chemotherapy; four cases, all M1), and surgery with medical therapy (one M1 case). Three-year progression-free survival was 57% (confidence interval [CI] 95%: 27-78) and was significantly better for patients with low-grade well differentiated (73 vs. 0%; p < 10-4) and localized (76 vs. 20%; p = .02) tumors. The two patients with pNECs died. Three-year overall survival was 92% (CI95%: 59-99) and was significantly better in patients with low-grade tumor (100 vs. 50%; p = 10-4). CONCLUSION Childhood pNENs occur more frequently in adolescents with CPS. Localized low-grade pNETs in children have a very good prognosis, whereas the treatment of high-grade and metastatic pNETs/pNECs should be better defined.
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Affiliation(s)
- Tiphaine Courtel
- Unité d'Onco-Hémato-Immunologie pédiatrique, CHU Angers, Angers, France
| | - Daniel Orbach
- SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris-Saclay University (PSL), Paris, France
| | - Brigitte Lacour
- French National Registry of Childhood Solid Tumors, CHU Nancy, Nancy, France
- Inserm UMR 1153, Centre of Research in Epidemiology and StatisticS (CRESS), Paris University, Epidemiology of Childhood and Adolescent Cancers Team (EPICEA), Paris, France
| | - Marianne Roumy
- Plateforme de recherche clinique pédiatrique, CHU Angers, Angers, France
| | - Ségolène Hescot
- Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France
| | - Emmanuel Desandes
- French National Registry of Childhood Solid Tumors, CHU Nancy, Nancy, France
- Inserm UMR 1153, Centre of Research in Epidemiology and StatisticS (CRESS), Paris University, Epidemiology of Childhood and Adolescent Cancers Team (EPICEA), Paris, France
| | - Pascale Philippe-Chomette
- Department of Pediatric Surgery, Assistance Publique des Hôpitaux de Paris, Hôpital Robert Debré, Paris, France
| | - Sabine Sarnacki
- Department of Pediatric Surgery, Urology and Transplantation, Necker-Enfants Malades Hospital, APHP, Université de Paris Cité, Paris, France
| | - Sabine Irtan
- APHP-Sorbonne University, Paris, France
- Department of Pediatric Visceral and Neonatal Surgery, Armand-Trousseau Children's Hospital, APHP, Paris, France
| | | | - Pierre Kubicek
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Angers, France
| | - Hervé Brisse
- Department of Imaging, Institut Curie, PSL University, Paris, France
| | - Brice Fresneau
- Gustave Roussy, Université Paris-Saclay, Department of Children and Adolescent Oncology, Paris-Saclay University, Paris-Sud University, CESP, INSERM, Villejuif, France
| | - Aurore Pire
- Department of Pediatric Surgery, Urology and Transplantation, Necker-Enfants Malades Hospital, APHP, Université de Paris Cité, Paris, France
| | - Yves Réguerre
- Unité d'oncologie et d'hématologie pédiatrique, CHU Saint Denis de la Réunion, Bellepierre, France
| | - Coralie Mallebranche
- Unité d'Onco-Hémato-Immunologie pédiatrique, CHU Angers, Angers, France
- Université d'Angers, Université de Nantes, CHU Angers, INSERM, CRCI2NA, SFR ICAT, Angers, France
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Shen K, Su W, Liang C, Shi D, Sun J, Yu R. Differentiating small (< 2 cm) pancreatic ductal adenocarcinoma from neuroendocrine tumors with multiparametric MRI-based radiomic features. Eur Radiol 2024; 34:7553-7563. [PMID: 38869639 DOI: 10.1007/s00330-024-10837-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/08/2024] [Accepted: 05/02/2024] [Indexed: 06/14/2024]
Abstract
OBJECTIVES To assess MR-based radiomic analysis in preoperatively discriminating small (< 2 cm) pancreatic ductal adenocarcinomas (PDACs) from neuroendocrine tumors (PNETs). METHODS A total of 197 patients (146 in the training cohort, 51 in the validation cohort) from two centers were retrospectively collected. A total of 7338 radiomics features were extracted from T2-weighted, diffusion-weighted, T1-weighted, arterial phase, portal venous phase and delayed phase imaging. The optimal features were selected by the Mann-Whitney U test, Spearman's rank correlation test and least absolute shrinkage and selection operator method and used to construct the radiomic score (Rad-score). Conventional radiological and clinical features were also assessed. Multivariable logistic regression was used to construct a radiological model, a radiomic model and a fusion model. RESULTS Nine optimal features were identified and used to build the Rad-score. The radiomic model based on the Rad-score achieved satisfactory results with AUCs of 0.905 and 0.930, sensitivities of 0.780 and 0.800, specificities of 0.906 and 0.952 and accuracies of 0.836 and 0.863 for the training and validation cohorts, respectively. The fusion model, incorporating CA19-9, tumor margins, pancreatic duct dilatation and the Rad-score, exhibited the best performance with AUCs of 0.977 and 0.941, sensitivities of 0.914 and 0.852, specificities of 0.954 and 0.950, and accuracies of 0.932 and 0.894 for the training and validation cohorts, respectively. CONCLUSIONS The MR-based Rad-score is a novel image biomarker for discriminating small PDACs from PNETs. A fusion model combining radiomic, radiological and clinical features performed very well in differentially diagnosing these two tumors. CLINICAL RELEVANCE STATEMENT A fusion model combining MR-based radiomic, radiological, and clinical features could help differentiate between small pancreatic ductal adenocarcinomas and pancreatic neuroendocrine tumors. KEY POINTS Preoperatively differentiating small pancreatic ductal adenocarcinomas (PDACs) and pancreatic neuroendocrine tumors (PNETs) is challenging. Multiparametric MRI-based Rad-score can be used for discriminating small PDACs from PNETs. A fusion model incorporating radiomic, radiological, and clinical features differentiated small PDACs from PNETs well.
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Affiliation(s)
- Keren Shen
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Weijie Su
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Chunmiao Liang
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Dan Shi
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Jihong Sun
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China
| | - Risheng Yu
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
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Ahmed TM, Zhu Z, Yasrab M, Blanco A, Kawamoto S, He J, Fishman EK, Chu L, Javed AA. Preoperative Prediction of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors Using a Combined CT Radiomics-Clinical Model. Ann Surg Oncol 2024; 31:8136-8145. [PMID: 39179862 DOI: 10.1245/s10434-024-16064-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/04/2024] [Indexed: 08/26/2024]
Abstract
BACKGROUND PanNETs are a rare group of pancreatic tumors that display heterogeneous histopathological and clinical behavior. Nodal disease has been established as one of the strongest predictors of patient outcomes in PanNETs. Lack of accurate preoperative assessment of nodal disease is a major limitation in the management of these patients, in particular those with small (< 2 cm) low-grade tumors. The aim of the study was to evaluate the ability of radiomic features (RF) to preoperatively predict the presence of nodal disease in pancreatic neuroendocrine tumors (PanNETs). PATIENTS AND METHODS An institutional database was used to identify patients with nonfunctional PanNETs undergoing resection. Pancreas protocol computed tomography was obtained, manually segmented, and RF were extracted. These were analyzed using the minimum redundancy maximum relevance analysis for hierarchical feature selection. Youden index was used to identify the optimal cutoff for predicting nodal disease. A random forest prediction model was trained using RF and clinicopathological characteristics and validated internally. RESULTS Of the 320 patients included in the study, 92 (28.8%) had nodal disease based on histopathological assessment of the surgical specimen. A radiomic signature based on ten selected RF was developed. Clinicopathological characteristics predictive of nodal disease included tumor grade and size. Upon internal validation the combined radiomics and clinical feature model demonstrated adequate performance (AUC 0.80) in identifying nodal disease. The model accurately identified nodal disease in 85% of patients with small tumors (< 2 cm). CONCLUSIONS Non-invasive preoperative assessment of nodal disease using RF and clinicopathological characteristics is feasible.
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Affiliation(s)
- Taha M Ahmed
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Zhuotun Zhu
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Mohammad Yasrab
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Alejandra Blanco
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Satomi Kawamoto
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Elliot K Fishman
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Linda Chu
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Ammar A Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, NYU Langone Grossman School of Medicine, New York, NY, USA.
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4
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Acher AW, Hallet J. Advances in Management of Nonfunctional Pancreas Neuroendocrine Tumors. Surg Clin North Am 2024; 104:1095-1111. [PMID: 39237166 DOI: 10.1016/j.suc.2024.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
This article presents updates in the surgical management of non-functional sporadic pancreas neuroendocrine tumors NET, including considerations for assessment of biologic behavior to support decision-making, indications for surgery, and surgical approaches tailored to the unique nature of neuroendocrine tumors.
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Affiliation(s)
- Alexandra W Acher
- Department of Surgery, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5
| | - Julie Hallet
- Department of Surgery, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada, M4N 3M5; Susan Leslie Clinic for Neuroendocrine Tumors, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
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5
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Perry RR, Feliberti EC, Hughes MS. Management of Pancreatic Neuroendocrine Tumors: Surgical Strategies and Controversies. Endocr Pract 2024; 30:908-916. [PMID: 39032831 DOI: 10.1016/j.eprac.2024.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 06/01/2024] [Accepted: 07/09/2024] [Indexed: 07/23/2024]
Abstract
OBJECTIVE Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors which are increasing in incidence. The management of these tumors continues to evolve. This review examines the current role of surgery in the treatment of these tumors. METHODS Studies published over the past 10 years were identified using several databases including PubMed, MEDLINE, and Science Direct. Search terms included PNETs, treatment, and surgery. Clinical practice guidelines and updates from several major groups were reviewed. RESULTS Surgery continues to have a major role in the treatment of sporadic functional and nonfunctional PNETs. Pancreas-sparing approaches are increasingly accepted as alternatives to formal pancreatic resection in selected patients. Options such as watch and wait or endoscopic ablation may be reasonable alternatives to surgery for non-functional PNETs < 2 cm in size. Surgical decision-making in multiple endocrine neoplasia type 1 patients remains complex and in some situations such as gastrinoma quite controversial. The role of surgery has significantly diminished in patients with advanced disease due to the advent of more effective systemic and liver-directed therapies. However, the optimal treatments and sequencing in advanced disease remain poorly defined, and it has been suggested that surgery is underutilized in these patients. CONCLUSIONS Surgery remains a major treatment modality for PNETs. Given the plethora of available treatments, ongoing controversies and the changing landscape, management has become increasingly complex. An experienced multidisciplinary team which includes surgery is essential to manage these patients.
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Affiliation(s)
- Roger R Perry
- Division of Surgical Oncology, Eastern Virginia Medical School, Norfolk, Virginia.
| | - Eric C Feliberti
- Division of Surgical Oncology, Eastern Virginia Medical School, Norfolk, Virginia
| | - Marybeth S Hughes
- Division of Surgical Oncology, Eastern Virginia Medical School, Norfolk, Virginia
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Albers MB, Sevcik M, Wiese D, Manoharan J, Rinke A, Jesinghaus M, Bartsch DK. Characteristics, therapy, and outcome of rare functioning pancreatic neuroendocrine neoplasms. Sci Rep 2024; 14:18507. [PMID: 39122816 PMCID: PMC11316089 DOI: 10.1038/s41598-024-68290-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 07/22/2024] [Indexed: 08/12/2024] Open
Abstract
Functioning pancreatic neuroendocrine neoplasms other than insulinomas and gastrinomas (rf-pNENs) are exceptionally rare tumours. Thus, their characteristics and long-term prognosis have not been well defined. This article aims to present data and experience from a single institution concerning this topic. Twelve of 216 (5.5%) patients with pNENs operated between 2002 and 2022 in the ENETS Centre of Excellence Marburg had rf-pNENs and their data were retrospectively analysed. We identified three vasoactive intestinal polypeptide producing pNENs, four glucagonomas and five calcitoninomas. The tumour could be visualised by preoperative imaging in all 12 patients, and six patients had distant metastases at the time of diagnosis. The tumour was located in the pancreatic tail in nine patients and the median tumour size was 82 (range 12-220) mm. Eleven patients underwent tumour resections (two robotic, nine conventional), nine of which were R0. After a median follow-up of 75 (range 1-247) months, six patients were alive, five of whom had no evidence of disease. All patients who remained disease-free had an initial R0 resection of the primary tumour and no initial liver involvement. This study sheds light on the distinct characteristics and outcomes of these exceedingly rare tumours, offering insights for improved understanding and management.
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Affiliation(s)
- Max B Albers
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Marburg, Philipps University Marburg, Marburg, Germany.
| | - Martina Sevcik
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Marburg, Philipps University Marburg, Marburg, Germany
| | - Dominik Wiese
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Marburg, Philipps University Marburg, Marburg, Germany
| | - Jerena Manoharan
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Marburg, Philipps University Marburg, Marburg, Germany
| | - Anja Rinke
- Department of Internal Medicine, Division of Gastroenterology and Endocrinology, University Hospital Marburg, Philipps University Marburg, Marburg, Germany
| | - Moritz Jesinghaus
- Institute of Pathology, University Hospital Marburg, Philipps University Marburg, Marburg, Germany
| | - Detlef K Bartsch
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Marburg, Philipps University Marburg, Marburg, Germany
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Partelli S, Battistella A, Andreasi V, Muffatti F, Tamburrino D, Pecorelli N, Crippa S, Balzano G, Falconi M. Critical appraisal of the adequacy of surgical indications for non-functioning pancreatic neuroendocrine tumours. BJS Open 2024; 8:zrae083. [PMID: 39107074 PMCID: PMC11303005 DOI: 10.1093/bjsopen/zrae083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 04/22/2024] [Accepted: 06/20/2024] [Indexed: 08/09/2024] Open
Abstract
BACKGROUND The lack of preoperative prognostic factors to accurately predict tumour aggressiveness in non-functioning pancreatic neuroendocrine tumours may result in inappropriate management decisions. This study aimed to critically evaluate the adequacy of surgical treatment in patients with resectable non-functioning pancreatic neuroendocrine tumours and investigate preoperative features of surgical appropriateness. METHODS A retrospective study was conducted on patients who underwent curative surgery for non-functioning pancreatic neuroendocrine tumours at San Raffaele Hospital (2002-2022). The appropriateness of surgical treatment was categorized as appropriate, potential overtreatment and potential undertreatment based on histologic features of aggressiveness and disease relapse within 1 year from surgery (early relapse). RESULTS A total of 384 patients were included. Among them, 230 (60%) received appropriate surgical treatment, whereas the remaining 154 (40%) underwent potentially inadequate treatment: 129 (34%) experienced potential overtreatment and 25 (6%) received potential undertreatment. The appropriateness of surgical treatment was significantly associated with radiological tumour size (P < 0.001), tumour site (P = 0.012), surgical technique (P < 0.001) and year of surgical resection (P < 0.001). Surgery performed before 2015 (OR 2.580, 95% c.i. 1.570 to 4.242; P < 0.001), radiological tumour diameter < 25.5 mm (OR 6.566, 95% c.i. 4.010 to 10.751; P < 0.001) and pancreatic body/tail localization (OR 1.908, 95% c.i. 1.119 to 3.253; P = 0.018) were identified as independent predictors of potential overtreatment. Radiological tumour size was the only independent determinant of potential undertreatment (OR 0.291, 95% c.i. 0.107 to 0.791; P = 0.016). Patients subjected to potential undertreatment exhibited significantly poorer disease-free survival (P < 0.001), overall survival (P < 0.001) and disease-specific survival (P < 0.001). CONCLUSIONS Potential overtreatment occurs in nearly one-third of patients undergoing surgery for non-functioning pancreatic neuroendocrine tumours. Tumour diameter emerges as the sole variable capable of predicting the risk of both potential surgical overtreatment and undertreatment.
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Affiliation(s)
- Stefano Partelli
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Anna Battistella
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Valentina Andreasi
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Muffatti
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Domenico Tamburrino
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Nicolò Pecorelli
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Stefano Crippa
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Gianpaolo Balzano
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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Battistella A, Tacelli M, Mapelli P, Schiavo Lena M, Andreasi V, Genova L, Muffatti F, De Cobelli F, Partelli S, Falconi M. Recent developments in the diagnosis of pancreatic neuroendocrine neoplasms. Expert Rev Gastroenterol Hepatol 2024; 18:155-169. [PMID: 38647016 DOI: 10.1080/17474124.2024.2342837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 04/10/2024] [Indexed: 04/25/2024]
Abstract
INTRODUCTION Pancreatic Neuroendocrine Neoplasms (PanNENs) are characterized by a highly heterogeneous clinical and biological behavior, making their diagnosis challenging. PanNENs diagnostic work-up mainly relies on biochemical markers, pathological examination, and imaging evaluation. The latter includes radiological imaging (i.e. computed tomography [CT] and magnetic resonance imaging [MRI]), functional imaging (i.e. 68Gallium [68 Ga]Ga-DOTA-peptide PET/CT and Fluorine-18 fluorodeoxyglucose [18F]FDG PET/CT), and endoscopic ultrasound (EUS) with its associated procedures. AREAS COVERED This review provides a comprehensive assessment of the recent advancements in the PanNENs diagnostic field. PubMed and Embase databases were used for the research, performed from inception to October 2023. EXPERT OPINION A deeper understanding of PanNENs biology, recent technological improvements in imaging modalities, as well as progresses achieved in molecular and cytological assays, are fundamental players for the achievement of early diagnosis and enhanced preoperative characterization of PanNENs. A multimodal diagnostic approach is required for a thorough disease assessment.
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Affiliation(s)
- Anna Battistella
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Matteo Tacelli
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreato-biliary Endoscopy and EUS Division, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Paola Mapelli
- Vita-Salute San Raffaele University, Milan, Italy
- Nuclear Medicine Department, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Valentina Andreasi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Luana Genova
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Muffatti
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco De Cobelli
- Vita-Salute San Raffaele University, Milan, Italy
- Radiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
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Javed AA, Zhu Z, Kinny-Köster B, Habib JR, Kawamoto S, Hruban RH, Fishman EK, Wolfgang CL, He J, Chu LC. Accurate non-invasive grading of nonfunctional pancreatic neuroendocrine tumors with a CT derived radiomics signature. Diagn Interv Imaging 2024; 105:33-39. [PMID: 37598013 PMCID: PMC10873069 DOI: 10.1016/j.diii.2023.08.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 08/21/2023]
Abstract
PURPOSE The purpose of this study was to develop a radiomics-signature using computed tomography (CT) data for the preoperative prediction of grade of nonfunctional pancreatic neuroendocrine tumors (NF-PNETs). MATERIALS AND METHODS A retrospective study was performed on patients undergoing resection for NF-PNETs between 2010 and 2019. A total of 2436 radiomic features were extracted from arterial and venous phases of pancreas-protocol CT examinations. Radiomic features that were associated with final pathologic grade observed in the surgical specimens were subjected to joint mutual information maximization for hierarchical feature selection and the development of the radiomic-signature. Youden-index was used to identify optimal cutoff for determining tumor grade. A random forest prediction model was trained and validated internally. The performance of this tool in predicting tumor grade was compared to that of EUS-FNA sampling that was used as the standard of reference. RESULTS A total of 270 patients were included and a fusion radiomic-signature based on 10 selected features was developed using the development cohort (n = 201). There were 149 men and 121 women with a mean age of 59.4 ± 12.3 (standard deviation) years (range: 23.3-85.0 years). Upon internal validation in a new set of 69 patients, a strong discrimination was observed with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.71-0.90) with corresponding sensitivity and specificity of 87.5% (95% CI: 79.7-95.3) and 73.3% (95% CI: 62.9-83.8) respectively. Of the study population, 143 patients (52.9%) underwent EUS-FNA. Biopsies were non-diagnostic in 26 patients (18.2%) and could not be graded due to insufficient sample in 42 patients (29.4%). In the cohort of 75 patients (52.4%) in whom biopsies were graded the radiomic-signature demonstrated not different AUC as compared to EUS-FNA (AUC: 0.69 vs. 0.67; P = 0.723), however greater sensitivity (i.e., ability to accurately identify G2/3 lesion was observed (80.8% vs. 42.3%; P < 0.001). CONCLUSION Non-invasive assessment of tumor grade in patients with PNETs using the proposed radiomic-signature demonstrated high accuracy. Prospective validation and optimization could overcome the commonly experienced diagnostic uncertainty in the assessment of tumor grade in patients with PNETs and could facilitate clinical decision-making.
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Affiliation(s)
- Ammar A Javed
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Surgery, New York University Langone Hospital, New York City, New York 10016, USA
| | - Zhuotun Zhu
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Benedict Kinny-Köster
- Department of Surgery, New York University Langone Hospital, New York City, New York 10016, USA
| | - Joseph R Habib
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Satomi Kawamoto
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Ralph H Hruban
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Elliot K Fishman
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Christopher L Wolfgang
- Department of Surgery, New York University Langone Hospital, New York City, New York 10016, USA
| | - Jin He
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Linda C Chu
- Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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10
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Bell-Allen N, McKay B, Kilburn D, Waters P, Cavallucci D. Robotic enucleation & uncinectomy of complex lesions of the proximal pancreas. ANZ J Surg 2023; 93:2897-2903. [PMID: 37795900 DOI: 10.1111/ans.18719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 09/14/2023] [Accepted: 09/17/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND Malignant tumours within the proximal pancreas traditionally require pancreaticoduodenectomy (PD) for cure. For smaller lesions with borderline malignant potential the risk/benefit of PD becomes difficult to justify. Robotic approaches to these lesions allow for parenchymal preserving resection with reduced complication profile without oncological compromise. METHODS A review of a single surgeons prospectively collated database across two institutions of consecutive robotic enucleations or parenchyma preserving resections of the proximal pancreas was performed between July 2018 and October 2021. Standard demographic data, preoperative variables, intraoperative parameters, post-operative outcomes, morbidity and mortality were recorded. RESULTS Thirteen patients (8 female and 5 male) underwent robotic enucleation (EN) (8) and/or uncinectomy (UN) (5) in the proximal pancreas. Mean BMI was 32(kg/m2 ). Three patients (21%) underwent preoperative prophylactic pancreatic duct stenting. One patient required conversion to open. The median operative time in the EN group was 170 min (108-224 min) and the UN group was 160 min (110-204 min). The majority (8) of lesions were pNETs. Three lesions were IPMNs, with 1 solitary fibrous tumour and a serous cystic neoplasm (SCN) respectively. Median tumour size was 23 mm (11-58 mm) in the EN group, and 27 mm (17-38 mm) in the UN group. Ten of 13 patients had an R0 resection. There was no mortality in our series. Four (31%) patients across both groups developed clinically relevant POPF while none developed new endocrine or exocrine insufficiency. Average outpatient follow-up has been 6 months (1-18 months). CONCLUSION A robotic approach in proximal parenchymal preserving pancreatectomy is expanding, safe and feasible.
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Affiliation(s)
- Nicholas Bell-Allen
- Department of HPB Surgery, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia
| | - Bartholomew McKay
- Department of HPB Surgery, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia
| | - Daniel Kilburn
- Department of HPB Surgery, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia
| | - Peadar Waters
- Department of HPB Surgery, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia
- Department of Surgery, Cork University Hospital, Cork, Ireland
| | - David Cavallucci
- Department of HPB Surgery, Royal Brisbane & Women's Hospital, Brisbane, Queensland, Australia
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11
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Pellat A, Barat M, Cottereau AS, Terris B, Coriat R. [Well-differentiated neuroendocrine tumors of the digestive tract: Focus on pancreatic neuroendocrine tumors]. Bull Cancer 2023; 110:955-967. [PMID: 36935319 DOI: 10.1016/j.bulcan.2023.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/16/2023] [Accepted: 03/01/2023] [Indexed: 03/19/2023]
Abstract
Pancreatic neuroendocrine tumors are rare tumors showing a rising incidence. They are well-differentiated tumors, classified by grade according to their Ki67 index value (grade 1 to 3). Pancreatic neuroendocrine tumors are mainly sporadic tumors but about 10% arise within endocrine tumor syndromes such as multiple endocrine neoplasia type 1. They can be responsible for functional syndromes or non-specific clinical symptoms depending on tumor extension. However, there is also an increase of incidental diagnoses of nonfunctional pancreatic neuroendocrine tumors with the widespread use of high-quality imaging techniques. About 50 % of pancreatic neuroendocrine tumors are diagnosed at a metastatic stage, with metastases often located in the liver. Chromogranin A, CT-scan and often an abdominal MRI, and functional imaging should be performed for tumor staging and follow-up. Imaging with PET/CT with 68Ga-labeled somatostatin analogues has the highest sensitivity for the diagnosis of pancreatic neuroendocrine tumors, while 18fluorodeoxyglucose PET/CT can sometimes be useful. Overall, they are rather indolent tumors with prolonged survival. Surgery is the recommended treatment in the localized setting, with the exception of small<2cm nonfunctional tumors that can be monitored with imaging techniques. For advanced tumors, there are several available treatments such as somatostatine analogues, chemotherapy, targeted therapies (sunitinib, everolimus), locoregional ablative therapies and Peptide Receptor Radiolabelled Therapy. The treatment strategy will depend on the initial tumor staging, tumor grade, aggressiveness and patient's choice.
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Affiliation(s)
- Anna Pellat
- AP-HP, hôpital Cochin, service de gastroentérologie et d'oncologie digestive, 27, rue du faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, 75006 Paris, France.
| | - Maxime Barat
- AP-HP, hôpital Cochin, service de radiologie, 27, rue du faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, 75006 Paris, France
| | - Anne-Ségolène Cottereau
- AP-HP, hôpital Cochin, service de médecine nucléaire, 27, rue du faubourg Saint-Jacques, 75014 Paris, France
| | - Benoit Terris
- AP-HP, hôpital Cochin, service d'anatomopathologie, 27, rue du faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, 75006 Paris, France
| | - Romain Coriat
- AP-HP, hôpital Cochin, service de gastroentérologie et d'oncologie digestive, 27, rue du faubourg Saint-Jacques, 75014 Paris, France; Université Paris Cité, 75006 Paris, France
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12
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Gangi A, Ferrone CR. What Is the Role of Lymph Node Resections in Small Islet Tumors? Adv Surg 2023; 57:47-58. [PMID: 37536861 DOI: 10.1016/j.yasu.2023.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
Well-differentiated nonfunctional pancreatic neuroendocrine tumors are often indolent neoplasms without lymph node (LN) metastasis at diagnosis. Patients with PNETs that are functional or >2 cm should have surgical resection as per the standard of care. However, in appropriately selected patients with NF PNETs <2 cm who are at low risk of LN metastasis, the extent of surgery and lymphadenectomy could be limited.
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Affiliation(s)
- Alexandra Gangi
- Gastrointestinal Tumor Program, Division of Surgical Oncology, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Boulevard North Tower, Suite 8215, Los Angeles, CA 90048, USA.
| | - Cristina R Ferrone
- Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Boulevard North Tower, Suite 8215, Los Angeles, CA 90048, USA
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13
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Alfagih A, AlJassim A, Alqahtani N, Vickers M, Goodwin R, Asmis T. Small Bowel Neuroendocrine Tumors-10-Year Experience of the Ottawa Hospital (TOH). Curr Oncol 2023; 30:7508-7519. [PMID: 37623025 PMCID: PMC10453717 DOI: 10.3390/curroncol30080544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 08/04/2023] [Accepted: 08/07/2023] [Indexed: 08/26/2023] Open
Abstract
(1) Aim: The prevalence and incidence of small bowel NETs have increased significantly over the past two decades. This study aims to report the 10-year experience of SB-NET management at a regional cancer center in Canada. (2) Materials and methods: We conducted a retrospective study of the clinical and pathological data of patients diagnosed with biopsy-proven SB-NET at The Ottawa Hospital (TOH), Ottawa, Canada between 2011 and 2021. We report the clinicopathological characteristics of these patients, as well as their outcomes data, including survival rates. (3) Results: Between 2011 and 2021, a total of 177 SB-NET cases were identified with 51% (n = 91) of cases being males. The most common sites of the tumors were the ileum 53% (n = 94), followed by the duodenum 9% (n = 16) and jejunum 7% (n = 12). Approximately 24% (n = 42) of the patients had symptoms for over six months prior to diagnosis and 18% (n = 32) had functioning SB-NET during the course of the disease. The majority of patients had locally advanced or metastatic disease at the time of presentation with stage III, and stage IV representing 42% (n = 75), and 41% (n = 73) respectively. The majority of patients 84% (n = 148) had well-differentiated histology. One hundred twenty patients underwent surgical resection of the primary tumor including 28 patients (16%) with limited metastatic disease. A total of 21 patients (18%) had recurrence after curative surgery. A total of 62 patients (35%) received first-line somatostatin analog (SSA) therapy for unresectable disease and seven patients had PRRT after progression on SSA. Five years OS was 100%, 91%, 97%, and 73% for stages I, II, III, and IV respectively. In univariate analysis, carcinoid symptoms, T stage, and differentiation were significant predictors for worse overall survival, but not RFS. (4) Conclusions: Compared to published historical controls, our study suggests improvement in the 5-year survival rate of SB-NETs over the last 10 years.
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Affiliation(s)
- Abdulhameed Alfagih
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1N 6N5, Canada; (A.A.); (A.A.); (N.A.); (M.V.); (R.G.)
- Medical Oncology Department, Comprehensive Cancer Center, King Fahad Medical City, Riyadh 11525, Saudi Arabia
| | - Abdulaziz AlJassim
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1N 6N5, Canada; (A.A.); (A.A.); (N.A.); (M.V.); (R.G.)
- Kuwait Cancer Control Center, Kuwait City 42262, Kuwait
| | - Nasser Alqahtani
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1N 6N5, Canada; (A.A.); (A.A.); (N.A.); (M.V.); (R.G.)
- King Abdulaziz Hospital, Ministry of National Guard Health Affairs, Al Ahsa 11426, Saudi Arabia
| | - Michael Vickers
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1N 6N5, Canada; (A.A.); (A.A.); (N.A.); (M.V.); (R.G.)
| | - Rachel Goodwin
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1N 6N5, Canada; (A.A.); (A.A.); (N.A.); (M.V.); (R.G.)
| | - Timothy Asmis
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1N 6N5, Canada; (A.A.); (A.A.); (N.A.); (M.V.); (R.G.)
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14
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Javed AA, Pulvirenti A, Razi S, Zheng J, Michelakos T, Sekigami Y, Thompson E, Klimstra DS, Deshpande V, Singhi AD, Weiss MJ, Wolfgang CL, Cameron JL, Wei AC, Zureikat AH, Ferrone CR, He J. Grading Pancreatic Neuroendocrine Tumors Via Endoscopic Ultrasound-guided Fine Needle Aspiration: A Multi-institutional Study. Ann Surg 2023; 277:e1284-e1290. [PMID: 35081574 PMCID: PMC9364076 DOI: 10.1097/sla.0000000000005390] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES To identify factors associated with concordance between World Health Organization (WHO) grade on cytological analysis (c-grade) and histopathological analysis (h-grade) of surgical specimen in patients with PanNETs and examine trends in utilization and accuracy of EUS-FNA in preoperatively predicting grade. BACKGROUND WHO grading system is prognostic in pancreatic neuroendo-crine tumors (PanNETs). The concordance between c-grade and h-grade is reported to be between 50% and 92%. METHODS A multicenter retrospective study was performed on patients undergoing resection for PanNETs at four high-volume centers between 2010 and 2019. Patients with functional or syndrome-associated tumors, and those receiving neoadjuvant therapy were excluded. Factors associated with concordance between c-grade and h-grade and trends of utilization of EUS-FNA were assessed. RESULTS Of 869 patients included, 517 (59.5%) underwent EUS-FNA; 452 (87.4%) were diagnostic of PanNETs and WHO-grade was reported for 270 (59.7%) patients. The concordance between c-grade and h-grade was 80.4% with moderate concordance ( Kc = 0.52, 95% CI: 0.41-0.63). Significantly higher rates of concordance were observed in patients with smaller tumors (<2 vs. ≥2cm, 81.1% vs. 60.4%, P = 0.005). Highest concordance (98.1%) was observed in patients with small tumors undergoing assessment between 2015-2019 with a near-perfect concordance ( Kc = 0.88, 95% CI: 0.61-1.00). An increase in the utilization of EUS-FNA (56.1% to 64.1%) was observed over the last 2 decades ( P = 0.017) and WHO-grade was more frequently reported (44.2% vs. 77.6%, P < 0.001). However, concordance between c-grade and h-grade did not change significantly (P = 0.118). CONCLUSION Recently, a trend towards increasing utilization and improved diagnostic accuracy of EUS-FNA has been observed in PanNETs. Concordance between c-grade and h-grade is associated with tumor size with near-perfect agreement when assessing PanNETs <2cm in size.
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Affiliation(s)
- Ammar A. Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA
| | - Alessandra Pulvirenti
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Samrah Razi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Jian Zheng
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | - Yurie Sekigami
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Elizabeth Thompson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - David S. Klimstra
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Vikram Deshpande
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Aatur D. Singhi
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | | | - John L. Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alice C. Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Amer H. Zureikat
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | | | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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15
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Choi JH, Paik WH, Lee SH, Lee MW, Cho IR, Ryu JK, Kim YT. Efficacy and predictive factors of endoscopic ultrasound-guided ethanol ablation in benign solid pancreatic tumors. Surg Endosc 2023:10.1007/s00464-022-09833-3. [PMID: 37079095 PMCID: PMC10338579 DOI: 10.1007/s00464-022-09833-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 12/16/2022] [Indexed: 04/21/2023]
Abstract
BACKGROUNDS AND OBJECTIVES Endoscopic ultrasound-guided ethanol ablation (EUS-EA) has recently been introduced for the management of solid pancreatic tumors, including pancreatic neuroendocrine tumors (PNETs) and solid pseudopapillary tumors (SPTs). The study aims to evaluate the efficacy and predictive factors for response of EUS-EA in solid pancreatic tumors. METHODS Between October 2015 and July 2021, 72 patients who underwent EUS-EA for solid pancreatic tumors were included. The study outcomes were to evaluate the efficacy of EUS-EA with complete remission (CR) and objective response, and their predictive factors. RESULTS During follow-up, 47 patients were diagnosed with PNETs and 25 with SPTs. Eight cases reached CR and 48 reached objective response. When compared with SPTs, PNETs showed similar duration to reach CR (median not reached; p = 0.319), but shorter duration to reach objective response (PNETs: median 20.6 months, 95%CI 10.26-30.88; SPTs: median 47.7 months, 95%CI 18.14-77.20; p = 0.018). Ethanol dosage > 0.35 ml/cm3 shortened the duration to reach CR (median not reached; p = 0.026) and objective response (median 42.5 months, 95%CI 25.34-59.66 vs. 19.6 months, 95%CI 10.17-29.09; p = 0.006). CR had no significant predictive factors, but PNETs showed significant predictive factors for objective response (HR 3.34, 95%CI 1.07-10.43; p = 0.038). Twenty-seven patients experienced adverse events, and there were two severe cases. CONCLUSION EUS-EA for pancreatic solid lesions seems feasible as a local treatment for patients who refuse or are unfit for surgery. Additionally, PNETs seem to be the better candidate for EUS-EA.
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Affiliation(s)
- Jin Ho Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Woo Hyun Paik
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Sang Hyub Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Min Woo Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - In Rae Cho
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Ji Kon Ryu
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yong-Tae Kim
- Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
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16
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van Beek DJ, Verschuur AVD, Brosens LAA, Valk GD, Pieterman CRC, Vriens MR. Status of Surveillance and Nonsurgical Therapy for Small Nonfunctioning Pancreatic Neuroendocrine Tumors. Surg Oncol Clin N Am 2023; 32:343-371. [PMID: 36925190 DOI: 10.1016/j.soc.2022.10.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Pancreatic neuroendocrine tumors (PNETs) occur in < 1/100,000 patients and most are nonfunctioning (NF). Approximately 5% occur as part of multiple endocrine neoplasia type 1. Anatomic and molecular imaging have a pivotal role in the diagnosis, staging and active surveillance. Surgery is generally recommended for nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) >2 cm to prevent metastases. For tumors ≤2 cm, active surveillance is a viable alternative. Tumor size and grade are important factors to guide management. Assessment of death domain-associated protein 6/alpha-thalassemia/mental retardation X-linked and alternative lengthening of telomeres are promising novel prognostic markers. This review summarizes the status of surveillance and nonsurgical management for small NF-PNETs, including factors that can guide management.
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Affiliation(s)
- Dirk-Jan van Beek
- Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Internal Mail Number G.04.228, PO Box 85500, Utrecht 3508 GA, the Netherlands
| | - Anna Vera D Verschuur
- Department of Pathology, University Medical Center Utrecht, Internal Mail Number G02.5.26, PO Box 85500, Utrecht 3508 GA, the Netherlands. https://twitter.com/annaveraverschu
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Internal Mail Number G4.02.06, PO Box 85500, Utrecht 3508 GA, the Netherlands
| | - Gerlof D Valk
- Department of Endocrine Oncology, University Medical Center Utrecht, Internal Mail Number Q.05.4.300, PO Box 85500, Utrecht 3508 GA, the Netherlands
| | - Carolina R C Pieterman
- Department of Endocrine Oncology, University Medical Center Utrecht, Internal Mail Number Q.05.4.300, PO Box 85500, Utrecht 3508 GA, the Netherlands.
| | - Menno R Vriens
- Department of Endocrine Surgical Oncology, University Medical Center Utrecht, Internal Mail Number G.04.228, PO Box 85500, Utrecht 3508 GA, the Netherlands
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17
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Konstantinoff KS, Morani AC, Hope TA, Bhosale PR, Francis IR, Yano M, Iravani A, Trikalinos NA, Itani M. Pancreatic neuroendocrine tumors: tailoring imaging to specific clinical scenarios. Abdom Radiol (NY) 2023; 48:1843-1853. [PMID: 36737523 DOI: 10.1007/s00261-022-03737-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/26/2022] [Accepted: 10/28/2022] [Indexed: 02/05/2023]
Abstract
The clinical and imaging presentation of pancreatic neuroendocrine tumors (PanNETs) is variable and depends on tumor grade, stage, and functional status. This degree of variability combined with a multitude of treatment options and imaging modalities results in complexity when choosing the most appropriate imaging studies across various clinical scenarios. While various guidelines exist in the management and evaluation of PanNETs, there is an overall lack of consensus and detail regarding optimal imaging guidelines and protocols. This manuscript aims to fill gaps where current guidelines may lack specificity regarding the choice of the most appropriate imaging study in the diagnosis, treatment planning, monitoring, and surveillance of PanNETs under various clinical scenarios.
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Affiliation(s)
- Katerina S Konstantinoff
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, 63110, USA
| | - Ajaykumar C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, The University of California, San Francisco, 185 Berry Street Lobby 6, San Francisco, CA, 94107, USA
| | - Priya R Bhosale
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Isaac R Francis
- Department of Radiology, Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI, 48109, USA
| | - Motoyo Yano
- Department of Radiology, Mayo Clinic Hospital, 5777 E. Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Amir Iravani
- Department of Radiology, University of Washington, 1959 NE Pacific St, Seattle, WA, 98195, USA
| | - Nikolaos A Trikalinos
- Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110, USA
| | - Malak Itani
- Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO, 63110, USA.
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Pellegrino F, Granata V, Fusco R, Grassi F, Tafuto S, Perrucci L, Tralli G, Scaglione M. Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists. Tomography 2023; 9:217-246. [PMID: 36828370 PMCID: PMC9958666 DOI: 10.3390/tomography9010018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/22/2023] [Accepted: 01/23/2023] [Indexed: 01/31/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes. Furthermore, they are primarily nonfunctioning, while, in the case of insulinomas, gastrinomas, glucagonomas, vipomas, and somatostatinomas, they produce hormones responsible for clinical syndromes. The GEP-NEN tumor grade and cell differentiation may result in different clinical behaviors and prognoses, with grade one (G1) and grade two (G2) neuroendocrine tumors showing a more favorable outcome than grade three (G3) NET and neuroendocrine carcinoma. Two critical issues should be considered in the NEN diagnostic workup: first, the need to identify the presence of the tumor, and, second, to define the primary site and evaluate regional and distant metastases. Indeed, the primary site, stage, grade, and function are prognostic factors that the radiologist should evaluate to guide prognosis and management. The correct diagnostic management of the patient includes a combination of morphological and functional evaluations. Concerning morphological evaluations, according to the consensus guidelines of the European Neuroendocrine Tumor Society (ENETS), computed tomography (CT) with a contrast medium is recommended. Contrast-enhanced magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is usually indicated for use to evaluate the liver, pancreas, brain, and bones. Ultrasonography (US) is often helpful in the initial diagnosis of liver metastases, and contrast-enhanced ultrasound (CEUS) can solve problems in characterizing the liver, as this tool can guide the biopsy of liver lesions. In addition, intraoperative ultrasound is an effective tool during surgical procedures. Positron emission tomography (PET-CT) with FDG for nonfunctioning lesions and somatostatin analogs for functional lesions are very useful for identifying and evaluating metabolic receptors. The detection of heterogeneity in somatostatin receptor (SSTR) expression is also crucial for treatment decision making. In this narrative review, we have described the role of morphological and functional imaging tools in the assessment of GEP-NENs according to current major guidelines.
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Affiliation(s)
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Naples, Italy
| | - Francesca Grassi
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80127 Naples, Italy
| | - Salvatore Tafuto
- S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori, IRCCS, Fondazione “G. Pascale”, 80131 Naples, Italy
| | - Luca Perrucci
- Ferrara Department of Interventional and Diagnostic Radiology, Ospedale di Lagosanto, Azienda AUSL, 44023 Ferrara, Italy
| | - Giulia Tralli
- Department of Radiology, Ospedale Santa Maria della Misericordia, 45100 Rovigo, Italy
| | - Mariano Scaglione
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
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19
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Contrast Enhanced EUS for Predicting Solid Pancreatic Neuroendocrine Tumor Grade and Aggressiveness. Diagnostics (Basel) 2023; 13:diagnostics13020239. [PMID: 36673049 PMCID: PMC9857765 DOI: 10.3390/diagnostics13020239] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/29/2022] [Accepted: 12/29/2022] [Indexed: 01/11/2023] Open
Abstract
Pancreatic neuroendocrine tumor (PNET) behavior assessment is a daily challenge for physicians. Modern PNET management varies from a watch-and-wait strategy to surgery depending on tumor aggressiveness. Therefore, the aggressiveness definition plays a pivotal role in the PNET work-up. The aggressiveness of PNETs is mainly based on the dimensions and histological grading, with sometimes a lack of specificity and sensibility. In the last twenty years, EUS has become a cornerstone in the diagnostic phase of PNET management for its high diagnostic yield and the possibility of obtaining a histological specimen. The number of EUS applications in the PNET work-up has been rapidly increasing with new and powerful possibilities. The application of contrast has led to an important step in PNET detection; in recent years, it has been gaining interesting applications in aggressiveness assessment. In this review, we underline the latest experiences and opportunities in the behavior assessment of PNETs using contact-enhanced EUS and contested enhanced harmonic EUS with a particular focus on the future application and possibility that these techniques could provide.
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Abstract
Neuroendocrine tumors (NETs) represent a heterogeneous group of tumors, with variable presentation based on the location of origin and degree of metastatic spread. There are no randomized control trials to guide surgical management; however, surgery remains the mainstay of treatment for most gastroenteropancreatic NETs based on retrospective studies. Metastatic disease is common at the time of presentation, particularly in the liver. There is a role for cytoreduction for improvement of both symptoms and survival. Robust prospective randomized data exists to support the use of medical therapies to improve progression-free and overall survival in patients with advanced, metastatic, and unresectable NETs.
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21
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Mori M, Palumbo D, Muffatti F, Partelli S, Mushtaq J, Andreasi V, Prato F, Ubeira MG, Palazzo G, Falconi M, Fiorino C, De Cobelli F. Prediction of the characteristics of aggressiveness of pancreatic neuroendocrine neoplasms (PanNENs) based on CT radiomic features. Eur Radiol 2022; 33:4412-4421. [PMID: 36547673 DOI: 10.1007/s00330-022-09351-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 10/13/2022] [Accepted: 11/29/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVES To predict tumor grade (G1 vs. G2/3), presence of distant metastasis (M+), metastatic lymph nodes (N+), and microvascular invasion (VI) of pancreatic neuroendocrine neoplasms (PanNEN) based on preoperative CT radiomic features (RFs), by applying a machine learning approach aimed to limit overfit. METHODS This retrospective study included 101 patients who underwent surgery for PanNEN; the entire population was split into training (n = 70) and validation cohort (n = 31). Based on a previously validated methodology, after tumor segmentation on contrast-enhanced CT, RFs were extracted from unenhanced CT images. In addition, conventional radiological and clinical features were combined with RFs into multivariate logistic regression models using minimum redundancy and a bootstrap-based machine learning approach. For each endpoint, models were trained and validated including only RFs (RF_model), and both (radiomic and clinicoradiological) features (COMB_model). RESULTS Twenty-five patients had G2/G3 tumor, 37 N+, and 14 M+ and 38 were shown to have VI. From a total of 182 RFs initially extracted, few independent radiomic and clinicoradiological features were identified. For M+ and G, the resulting models showed moderate to high performances: areas under the curve (AUC) for training/validation cohorts were 0.85/0.77 (RF_model) and 0.81/0.81 (COMB_model) for M+ and 0.67/0.72 and 0.68/0.70 for G. Concerning N+ and VI, only the COMB_model could be built, with poorer performance for N+ (AUC = 0.72/0.61) compared to VI (0.82/0.75). For all endpoints, the negative predictive value was good (≥ 0.75). CONCLUSIONS Combining few radiomic and clinicoradiological features resulted in presurgical prediction of histological characteristics of PanNENs. Despite the limited risk of overfit, external validations are warranted. KEY POINTS • Histology is the only tool currently available allowing characterization of PanNEN biological characteristics important for prognostic assessment; significant limitations to this approach exist. • Based upon preoperative contrast-enhanced CT images, a machine learning approach optimized to favor models' generalizability was successfully applied to train predictive models for tumor grading (G1 vs. G2/3), microvascular invasion, metastatic lymph nodes, and distant metastatic spread. • Moderate to high discriminative models (AUC: 0.67-0.85) based on few parameters (≤ 3) showing high negative predictive value (0.75-0.98) were generated and then successfully validated.
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22
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Javed AA, Pulvirenti A, Zheng J, Michelakos T, Sekigami Y, Razi S, McIntyre CA, Thompson E, Klimstra DS, Deshpande V, Singhi AD, Weiss MJ, Wolfgang CL, Cameron JL, Wei AC, Zureikat AH, Ferrone CR, He J. A novel tool to predict nodal metastasis in small pancreatic neuroendocrine tumors: A multicenter study. Surgery 2022; 172:1800-1806. [PMID: 36192215 DOI: 10.1016/j.surg.2022.08.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/25/2022] [Accepted: 08/19/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Nonfunctional pancreatic neuroendocrine tumors display a wide range of biological behavior, and nodal disease is associated with metastatic disease and poorer survival. The aim of this study was to develop a tool to predict nodal disease in patients with small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors. METHODS A multicenter retrospective study was performed on patients undergoing resection for small nonfunctional pancreatic neuroendocrine tumors. Patients with genetic syndromes, metastatic disease at diagnosis, neoadjuvant therapy, or positive resection margin were excluded. Factors associated with nodal disease were identified to develop a predictive model. Internal validation was performed using bootstrap with 1,000 resamples. RESULTS Nodal disease was observed in 39 (11.1%) of the 353 patients included. Presence of nodal disease was significantly associated with lower 5-year disease-free survival (71.6% vs 96.2%, P < .001). Two predictors were strongly associated with nodal disease: G2 grade (odds ratio: 3.51, 95% confidence interval: 1.71-7.22, P = .001) and tumor size (per mm increase, odds ratio: 1.14, 95% confidence interval: 1.03-1.25, P = .009). Adequate discrimination was observed with an area under the curve of 0.71 (95% confidence interval: 0.63-0.80). Based on risk distribution, 3 risk groups of nodal disease were identified; low (<5%), intermediate (≥5% to <20%), and high (≥20%) risk. The observed mean risk of nodal disease was 3.7% in the low-risk patients, 9.6% in the intermediate-risk patients, and 30.4% in the high-risk patients (P < .001). The 10-year disease-free survival in the low, intermediate, and high-risk groups was 100%, 88.8%, and 50.1%, respectively. CONCLUSION Our model using tumor grade and size can predict nodal disease in small nonfunctional pancreatic neuroendocrine tumors. Integration of this tool into clinical practice could help guide management of these patients.
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Affiliation(s)
- Ammar A Javed
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. http://www.twitter.com/ammar_asrar
| | | | - Jian Zheng
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | - Yurie Sekigami
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Samrah Razi
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Caitlin A McIntyre
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Elizabeth Thompson
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - David S Klimstra
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Vikram Deshpande
- Department of Surgery, Massachusetts General Hospital, Boston, MA
| | - Aatur D Singhi
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | | | - John L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Alice C Wei
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh School of Medicine, PA
| | | | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
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23
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Persano I, Parlagreco E, La Salvia A, Audisio M, Volante M, Buttigliero C, Scagliotti GV, Brizzi MP. Synchronous or metachronous presentation of pancreatic neuroendocrine tumor versus secondary lesion to pancreas in patients affected by renal cell carcinoma. Systematic review. Semin Oncol 2022; 49:476-481. [PMID: 36759234 DOI: 10.1053/j.seminoncol.2023.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 01/17/2023] [Accepted: 01/17/2023] [Indexed: 02/05/2023]
Abstract
The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two malignancies share both radiological and cytopathological features, making the differential diagnosis very challenging. In this review, we collected all cases of concurrent diagnosis of localized panNET and RCC, with or without VHL, as reported in the literature to date. We aimed to provide an insight into the differential diagnosis between panNET and RCC pancreatic metastasis with a focus on the optimal therapeutic algorithm depending on the diagnosis. We performed literature research in PubMed library databases for articles about coexisting panNET and RCC published from 2001 to 2018. We selected nine articles with a total of 13 patients, including one treated at our institution. Patients' median age was 49 years and eight out of 13 patients were women. VHL was diagnosed in nine cases. Most patients underwent radical nephrectomy for RCC (9/13) and a clear cell renal carcinoma variant was identified in six cases. The diagnosis of panNET was synchronous with RCC detection in nine cases and metachronous in four cases. The diameter of the pancreatic lesion was >2 cm in six cases. In two cases the panNET was misdiagnosed as metastatic RCC by radiological tests. Somatostatin receptor scanning was performed only in our patient (Octreoscan) showing intense uptake in the pancreatic mass. Endoscopic ultrasound fine needle aspiration of the pancreatic lesion was performed in four patients: in two cases the panNET was confused with metastatic RCC by cytological analysis. Most patients underwent pancreatic surgery (10/13) without histological confirmation. Clear cell panNET was recognized in six cases, while mixed neuroendocrine non-neuroendocrine neoplasm was diagnosed in one patient. Immunohistochemistry (IHC) staining showed positivity to typical neuroendocrine markers (chromogranin A and synaptophysin) in all reported tested cases (8/8). Three patients underwent systemic treatment: two patients received sunitinib and one patient interleukin-2 (IL-2). Other neoplasms were observed in seven patients, of whom six were affected by VHL syndrome. When neoplastic lesions are recognized in both the kidney and pancreas, panNET and RCC pancreatic metastasis are often misdiagnosed due to similar radiological and cytopathological features. An accurate differential diagnosis is crucial and IHC plays a central role in distinguishing the two entities. The therapeutic algorithm may change depending on the diagnosis: while pancreatic RCC metastases benefit from resection, in panNETs and VHL the indication for surgery must be carefully evaluated.
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Affiliation(s)
- Irene Persano
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy.
| | - Elena Parlagreco
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
| | - Anna La Salvia
- National Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, Italy
| | - Marco Audisio
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
| | - Marco Volante
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
| | - Consuelo Buttigliero
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
| | | | - Maria Pia Brizzi
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
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24
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Partelli S, Massironi S, Zerbi A, Niccoli P, Kwon W, Landoni L, Panzuto F, Tomazic A, Bongiovanni A, Kaltsas G, Sauvanet A, Bertani E, Mazzaferro V, Caplin M, Armstrong T, Weickert MO, Ramage J, Segelov E, Butturini G, Staettner S, Cives M, Frilling A, Moulton CA, He J, Boesch F, Selberheer A, Twito O, Castaldi A, De Angelis CG, Gaujoux S, Holzer K, Wilson CH, Almeamar H, Vigia E, Muffatti F, Lucà M, Lania A, Ewald J, Kim H, Salvia R, Rinzivillo M, Smid A, Gardini A, Tsoli M, Hentic O, Colombo S, Citterio D, Toumpanakis C, Ramsey E, Randeva HS, Srirajaskanthan R, Croagh D, Regi P, Gasteiger S, Invernizzi P, Ridolfi C, Giovannini M, Jang JY, Bassi C, Falconi M. Management of asymptomatic sporadic non-functioning pancreatic neuroendocrine neoplasms no larger than 2 cm: interim analysis of prospective ASPEN trial. Br J Surg 2022; 109:1186-1190. [PMID: 35986682 PMCID: PMC10364756 DOI: 10.1093/bjs/znac267] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/18/2022] [Accepted: 07/14/2022] [Indexed: 12/31/2022]
Affiliation(s)
- Stefano Partelli
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.,Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Sara Massironi
- Division of Gastroenterology and Centre for Autoimmune Liver Diseases, San Gerardo Hospital, Monza, Italy.,Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Patricia Niccoli
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Wooil Kwon
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Luca Landoni
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Francesco Panzuto
- Digestive Disease Unit, ENETS Centre of Excellence, Sant' Andrea University Hospital, Rome, Italy
| | - Ales Tomazic
- Department of Abdominal Surgery, University Medical Centre, Ljubijana, Slovenia
| | - Alberto Bongiovanni
- Osteoncology and Rare Tumours Centre (CDO-TR), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
| | - Gregory Kaltsas
- First Propaedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Alain Sauvanet
- Department of Pancreatology, Hôpital Beaujon, University of Paris, Paris, France
| | - Emilio Bertani
- Division of Gastrointestinal Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal and Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute) and Università degli Studi di Milano, Milan, Italy
| | - Martyn Caplin
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Thomas Armstrong
- Department of Hepatobiliary Surgery, Wessex NET Group ENETS Centre of Excellence, University Hospital Southampton, Southampton, UK
| | - Martin O Weickert
- ARDEN NET Centre, ENETS Centre of Excellence, University Hospitals Coventry and Warwickshire NHS Trust and Warwick Medical School, University of Warwick, Coventry, UK
| | - John Ramage
- Kings Health Partners NET Centre, Kings College Hospital London, London, UK
| | - Eva Segelov
- Department of Oncology and Surgery (School of Clinical Sciences at Monash Health), Monash University, Clayton, Victoria, Australia
| | | | - Stefan Staettner
- Department of General, Visceral and Vascular Surgery, Salzkammergutklinikum Vöcklabruck, Vöcklabruck, Austria
| | - Mauro Cives
- Department of Biomedical Sciences and Human Oncology, University of Bari 'Aldo Moro', Bari, Italy
| | - Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Carol Anne Moulton
- Division of General Surgery, University of Toronto, Toronto, Ontario, Canada.,Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medical, Baltimore, Maryland, USA
| | - Florian Boesch
- Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany
| | - Andreas Selberheer
- Section Endocrine Surgery, Division of General Surgery, Department of Surgery, Medical University, Vienna, Austria
| | - Orit Twito
- Endocrine Institute, Meir Medical Center, Kfar-Sava, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Antonio Castaldi
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Claudio G De Angelis
- Gastroenterology Unit, Department of Medical Sciences, City of Health and Science Hospital, Turin, Italy
| | - Sebastien Gaujoux
- Department of Digestive, Hepatobiliary and Endocrine Surgery, Paris Sorbonne University, Pitiè Salpétrière Hospital, Paris, France
| | - Katharina Holzer
- Department of Visceral-, Thoracic- and Vascular Surgery, Section of Endocrine Surgery, University Hospital Marburg (UKGM), Marburg, Germany
| | - Colin H Wilson
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle upon Tyne, UK
| | - Hussein Almeamar
- National NET Centre and ENETS Centre of Excellence, St Vincent's University Hospital, Dublin, Ireland
| | - Emanuel Vigia
- Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, CHULC, Lisbon, Portugal
| | - Francesca Muffatti
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.,Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Martina Lucà
- Division of Gastroenterology and Centre for Autoimmune Liver Diseases, San Gerardo Hospital, Monza, Italy.,Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Andrea Lania
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Jacques Ewald
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Hongbeom Kim
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, ENETS Centre of Excellence, Sant' Andrea University Hospital, Rome, Italy
| | - Alojz Smid
- Department of Gastroenterology and Hepatology, University Medical Centre Ljubijana, Ljubljana, Slovenia
| | - Andrea Gardini
- General and Oncological Surgery Unit, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Marina Tsoli
- First Propaedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Olivia Hentic
- Department of Pancreatology, Hôpital Beaujon, University of Paris, Paris, France
| | - Samuele Colombo
- Division of Gastrointestinal Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Davide Citterio
- Gastrointestinal and Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione, IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute) and Università degli Studi di Milano, Milan, Italy
| | - Christos Toumpanakis
- ENETS Centre of Excellence, Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - Emma Ramsey
- Department of Hepatobiliary Surgery, Wessex NET Group ENETS Centre of Excellence, University Hospital Southampton, Southampton, UK
| | | | | | - Daniel Croagh
- Department of Oncology and Surgery (School of Clinical Sciences at Monash Health), Monash University, Clayton, Victoria, Australia
| | - Paolo Regi
- Department of Surgery, Pederzoli Hospital, Peschiera del Garda, Italy
| | - Silvia Gasteiger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Pietro Invernizzi
- Division of Gastroenterology and Centre for Autoimmune Liver Diseases, San Gerardo Hospital, Monza, Italy.,Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
| | - Cristina Ridolfi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Hospital-IRCCS, Rozzano, Milan, Italy
| | - Marc Giovannini
- Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France
| | - Jin-Young Jang
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Claudio Bassi
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Massimo Falconi
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.,Pancreas Translational and Clinical Research Centre, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
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25
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Abe K, Kitago M, Iwasaki E, Yagi H, Abe Y, Hasegawa Y, Hori S, Tanaka M, Nakano Y, Kitagawa Y. Reconsideration of operative indications in pancreatic neuroendocrine neoplasms. World J Surg Oncol 2022; 20:366. [PMID: 36397094 PMCID: PMC9673351 DOI: 10.1186/s12957-022-02834-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 11/05/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The incidence of pancreatic neuroendocrine neoplasm (PNEN) has been increasing. Resection is typically indicated for PNEN, regardless of its size; however, the indications for its resection are controversial. This study aimed to evaluate the treatment results of surgical resection of PNEN at our institute. METHODS In this single-center, retrospective, case-control study, 87 patients who underwent PNEN resection and 17 patients with PNEN who did not undergo surgical resection between 1993 and 2020 were included in this study. Clinical characteristics and outcomes were reviewed and statistically compared. Survival was also estimated for the patients in each cohort. RESULTS Seventeen patients who underwent resection (20%) had lymph node metastasis. Tumors measuring ≥ 2.0 cm and multiple lesions were identified as independent predictors for lymph node metastasis (odds ratio [OR] 17.3, 95% confidence interval [CI] 3.0-100.0, p = 0.001 and OR 8.7, 95% CI 1.5-52.0, p = 0.018, respectively). There was a significant difference in the survival curves depending on the presence or absence of lymph node metastasis (5-year overall survival 74.7% vs. 94.3%, p < 0.001; 5-year recurrence-free survival: 66.3% vs. 93.6%, p < 0.001). All 17 PNEN cases under observation with a median 8 mm (range 5-23) tumor size for a median of 34 (range 2.4-114) months showed slight morphological change with a median tumor growth rate of 0.15 mm (range 0-3.33) per year. CONCLUSION Patients with tumors measuring ≥ 2.0 cm have a high probability of lymph node metastasis or recurrence, thereby requiring resection. PNEN measuring < 1.0 cm may be acceptable for observation.
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Affiliation(s)
- Kodai Abe
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Eisuke Iwasaki
- Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hiroshi Yagi
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yasushi Hasegawa
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Shutaro Hori
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Masayuki Tanaka
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yutaka Nakano
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, 160-8582, Japan
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26
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Guo N, Liang Z, Xiong LJ. Clinicopathological characteristics, survival outcomes and prognostic factors in the cT1N0M0 pancreatic neuroendocrine tumors: A SEER-based study. Medicine (Baltimore) 2022; 101:e31019. [PMID: 36254020 PMCID: PMC9575711 DOI: 10.1097/md.0000000000031019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Small nonfunctional pancreatic neuroendocrine tumors ≤2 cm have different biological features, and there is no gold standard treatment for them. This study aimed to assess the risk of malignancy of small non-functional pancreatic neuroendocrine tumors and their outcomes after radical resection. The optimal management of small, incidentally detected pancreatic neuroendocrine tumors is controversial, with the aim of identifying factors predicting survival in patients with clinical stage T1N0M0 (cT1N0M0) pancreatic neuroendocrine tumors and whether surgical treatment improves survival. Using the Surveillance, Epidemiology, and End Results database, we identified 637 patients with cT1N0M0 pancreatic neuroendocrine tumors from 2010 to 2015, including clinicopathological characteristics, treatment modalities, and outcome data. From the surveillance, epidemiology, and end results database of 637 patients with cT1N0M0 PNENs, 564 were treated surgically. Age (P = .000), sex (P < .001), and surgery (P < .001) were independent risk factors affecting survival. Patients who have undergone surgery, women and young adults have a higher overall survival rate. The following independent prognostic predictors for cT1N0M0 pNENs were identified: age, sex, and surgery. At last, we concluded that Surgery can increase the overall survival of pancreatic neuroendocrine tumors in T1N0M0.
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Affiliation(s)
- Nian Guo
- Department of Endocrinology, Second Clinical School of Medicine, Jinan University Guangdong, China
| | - Zhen Liang
- Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China
- Correspondence: Zhen Liang, Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), 1017 Dongmen North Road, Luohu District, Shenzhen, Guangdong, 518000, China (e-mail: )
| | - Li Jiao Xiong
- Department of Geriatrics, Second Clinical School of Medicine, Jinan University Guangdong, Guangzhou, Guangdong, China
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27
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Fernandes CJ, Leung G, Eads JR, Katona BW. Gastroenteropancreatic Neuroendocrine Tumors. Gastroenterol Clin North Am 2022; 51:625-647. [PMID: 36153114 DOI: 10.1016/j.gtc.2022.06.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.
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Affiliation(s)
- Conrad J Fernandes
- Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Galen Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Jennifer R Eads
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA.
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28
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Bell PD, Singhi AD. Integrating Molecular Analysis into the Pathologic Evaluation of Pancreatic Cysts. Surg Pathol Clin 2022; 15:455-468. [PMID: 36049828 DOI: 10.1016/j.path.2022.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
The development of cross-sectional imaging techniques has enhanced the detection of pancreatic cystic lesions (PCLs). PCLs are found in approximately 2% of the general population, often as incidentally detected lesions on computed tomography or MRI during the evaluation of other medical conditions. Broadly, PCLs are classified as mucinous or nonmucinous. Mucinous PCLs include mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. Nonmucinous PCLs include pseudocysts, serous cystadenomas, solid pseudopapillary neoplasms, and cystic pancreatic neuroendocrine tumors, as well as cystic acinar cell carcinoma, cystic degeneration of pancreatic ductal adenocarcinoma, lymphoepithelial cyst, and others.
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Affiliation(s)
- Phoenix D Bell
- Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St. Pittbsurgh, PA 15213, USA.
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St. Pittbsurgh, PA 15213, USA
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Tan Q, Chengzhi X, Chen Y. The management of small nonfunctional pancreatic neuroendocrine tumors: It's time to define the high-risk features. J Surg Oncol 2022; 126:1135-1136. [PMID: 36004442 DOI: 10.1002/jso.27025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 07/11/2022] [Accepted: 07/14/2022] [Indexed: 11/10/2022]
Affiliation(s)
- Qingquan Tan
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiang Chengzhi
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yonghua Chen
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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30
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Wiese D, Bartsch DK. [Controversy: asymptomatic small pancreatic neuroendocrine neoplasms : Current standards in diagnostics and treatment]. CHIRURGIE (HEIDELBERG, GERMANY) 2022; 93:739-744. [PMID: 35913627 DOI: 10.1007/s00104-022-01647-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/20/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND For the increasingly diagnosed entity of small asymptomatic, sporadic, nonfunctional, pancreatic neuroendocrine neoplasms (pNEN), a negligible or at least unclear prognostic relevance of the disease for patient survival has often been observed. OBJECTIVE Safety and acceptance of a watch-and-wait strategy versus surgical resection for small, asymptomatic nonfunctional (NF) pNEN. METHODS Presentation and evaluation of the relevant literature as well as the corresponding national and European guidelines. RESULTS Surgery of small NF-pNEN shows complication rates of 15-32% (Clavien-Dindo ≥ 3) and a mortality of 3.6%. Even for pNEN < 2 cm the presence of lymph node metastases has been observed in 11% of cases, while their prognostic relevance in G1-pNEN compared with active surveillance remains unclear. On average 14% of patients under active surveillance for small NF-pNEN, underwent a resection. Relevant tumor growth during surveillance was found in < 20% of cases. In all well-selected surveillance cohorts no metachronous lymphatic or distant metastases occurred during active surveillance and especially no cases of a metachronous no longer curable disease. CONCLUSION Even small asymptomatic NF-pNEN have a certain metastatic potential but the clinical relevance has prospectively not yet been clearly determined. Controlled surveillance of these tumors is at least an alternative to immediate tumor resection. Especially patients above 70 years old do not seem to benefit from resection. The pros and cons of a resection should therefore be individually evaluated with the patient.
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Affiliation(s)
- D Wiese
- Klinik für Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Baldingerstraße, 35043, Marburg, Deutschland.
| | - D K Bartsch
- Klinik für Viszeral‑, Thorax- und Gefäßchirurgie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Baldingerstraße, 35043, Marburg, Deutschland
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31
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Bösch F, Ghadimi M, Angele MK. Personalisierte Resektionsverfahren bei neuroendokrinen Neoplasien des Pankreas. Zentralbl Chir 2022; 147:264-269. [DOI: 10.1055/a-1823-1275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungNeuroendokrine Neoplasien des Pankreas (pNEN) haben eine steigende Inzidenz und erhalten klinisch dadurch eine immer höhere Relevanz. Neben den hormonell inaktiven pNEN gibt es die
hormonproduzierenden Tumoren, und sowohl die inaktiven als auch die aktiven pNEN können entweder sporadisch oder hereditär vorkommen. Die Behandlung orientiert sich an tumorassoziierten
Faktoren, aber auch an individuellen patienteneigenen Gegebenheiten. Für die Behandlung sind individuelle maßgeschneiderte Konzepte notwendig, welche die jeweiligen Faktoren und
Gegebenheiten berücksichtigen.
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Affiliation(s)
- Florian Bösch
- Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen, Gottingen, Deutschland
| | - Michael Ghadimi
- Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Universitätsmedizin Göttingen, Gottingen, Deutschland
| | - Martin K. Angele
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, München, Deutschland
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Zhang XF, Xue F, Wu Z, Lopez-Aguiar AG, Poultsides G, Makris E, Rocha F, Kanji Z, Weber S, Fisher A, Fields R, Krasnick BA, Idrees K, Smith PM, Cho C, Beems M, Lyu Y, Maithel SK, Pawlik TM. Development and Validation of a Modified Eighth AJCC Staging System for Primary Pancreatic Neuroendocrine Tumors. Ann Surg 2022; 275:e773-e780. [PMID: 32511134 PMCID: PMC10188291 DOI: 10.1097/sla.0000000000004039] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system. BACKGROUND Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial. METHODS Data from the SEER registry (1975-2016) (n = 3303) and a multi-institutional database (2000-2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (no LNM), N1 (1-3 LNM), and N2 (≥4 LNM), but adopting a new stage classification. RESULTS The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts. CONCLUSION A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging.
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Affiliation(s)
- Xu-Feng Zhang
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Feng Xue
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zheng Wu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | | | | | - Flavio Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Zaheer Kanji
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Sharon Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Alexander Fisher
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Ryan Fields
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Bradley A Krasnick
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - Paula M Smith
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - Cliff Cho
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Megan Beems
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan
| | - Yi Lyu
- Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Timothy M Pawlik
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
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Dai M, Mullins CS, Lu L, Alsfasser G, Linnebacher M. Recent advances in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Surg 2022; 14:383-396. [PMID: 35734622 PMCID: PMC9160679 DOI: 10.4240/wjgs.v14.i5.383] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/17/2022] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a rare group of tumors originating from neuroendocrine cells of the digestive system. Their incidence has increased over the last decades. The specific pathogenetic mechanisms underlying GEP-NEN development have not been completely revealed. Unfunctional GEP-NENs are usually asymptomatic; some grow slowly and thus impede early diagnosis, which ultimately results in a high rate of misdiagnosis. Therefore, many GEP-NEN patients present with later staged tumors. Motivated hereby, research attention for diagnosis and treatment for GEP-NENs increased in recent years. The result of which is great progress in clinical diagnosis and treatment. According to the most recent clinical guidelines, improved grading standards can accurately define poorly differentiated grade 3 neuroendocrine tumors and neuroendocrine carcinomas (NECs), which are subclassified into large and small cell NECs. Combining different functional imaging methods facilitates precise diagnosis. The expression of somatostatin receptors helps to predict prognosis. Genetic analyses of mutations affecting death domain associated protein (DAXX), multiple endocrine neoplasia type 1 (MEN 1), alpha thalassemia/intellectual disability syndrome X-linked (ATRX), retinoblastoma transcriptional corepressor 1 (RB 1), and mothers against decapentaplegic homolog 4 (SMAD 4) help distinguishing grade 3 NENs from poorly differentiated NECs. The aim of this review is to summarize the latest research progress on diagnosis and treatment of GEP-NENs.
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Affiliation(s)
- Meng Dai
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Christina S Mullins
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Lili Lu
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Guido Alsfasser
- Clinic of General Surgery, Rostock University Medical Center, 18057 Rostock, Germany
| | - Michael Linnebacher
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
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Perinel J, Nappo G, Zerbi A, Heidsma CM, Nieveen van Dijkum EJM, Han HS, Yoon YS, Satoi S, Demir IE, Friess H, Vashist Y, Izbicki J, Muller AC, Gloor B, Sandini M, Gianotti L, Subtil F, Adham M. Sporadic nonfunctional pancreatic neuroendocrine tumors: Risk of lymph node metastases and aggressiveness according to tumor size: A multicenter international study. Surgery 2022; 172:975-981. [PMID: 35623953 DOI: 10.1016/j.surg.2022.04.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/25/2022] [Accepted: 04/06/2022] [Indexed: 01/08/2023]
Abstract
BACKGROUND Although the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival. METHODS Resected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999-2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence. RESULTS Overall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46-2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm. CONCLUSION In resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients.
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Affiliation(s)
- Julie Perinel
- Department of Digestive Surgery, E. Herriot Hospital, Hospices Civils de Lyon, Lyon Sud Faculty of Medicine, UCBL1, Lyon, France.
| | - Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS Rozzano, Milan, Italy
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Charlotte M Heidsma
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, The Netherlands
| | | | - Ho Seong Han
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea
| | - Yoo-Seok Yoon
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Republic of Korea
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Osaka, Japan; Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Ihsan Ekin Demir
- Department of Surgery, Technical University Munich Faculty of Medicine, Munchen, Germany
| | - Helmut Friess
- Department of Surgery, Technical University Munich Faculty of Medicine, Munchen, Germany
| | - Yogesh Vashist
- Medias Klinikum, Centre for Surgical Oncology, Burghausen, Germany
| | - Jakob Izbicki
- General, Visceral, and Thoracic Surgery Department, Clinic University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Beat Gloor
- University Hospital Bern Inselspital Bern, Switzerland
| | - Marta Sandini
- School of Medicine and Surgery, University of Milano-Bicocca and Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Luca Gianotti
- School of Medicine and Surgery, University of Milano-Bicocca and Department of Surgery, San Gerardo Hospital, Monza, Italy
| | - Fabien Subtil
- UCBLUMR CNRS 5558 - LBBE, Service de Biostatistiques, Hospices Civils de Lyon, France
| | - Mustapha Adham
- Department of Digestive Surgery, E. Herriot Hospital, Hospices Civils de Lyon, Lyon Sud Faculty of Medicine, UCBL1, Lyon, France
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Clinicopathological Characteristics of Nonfunctional Pancreatic Neuroendocrine Neoplasms and the Effect of Surgical Treatment on the Prognosis of Patients with Liver Metastases: A Study Based on the SEER Database. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3689895. [PMID: 35720036 PMCID: PMC9200579 DOI: 10.1155/2022/3689895] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/23/2022] [Accepted: 04/11/2022] [Indexed: 12/13/2022]
Abstract
Background The incidence of nonfunctional pancreatic neuroendocrine neoplasms (NF-pNENs) has been increasing annually. This study is aimed at investigating the clinicopathological characteristics and high-risk factors of NF-pNENs and the influence of surgical treatment on the prognosis of NF-pNEN patients with liver metastases. Methods pNEN patients in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. This study analyzed patients diagnosed with NF-pNENs from 2000 to 2017 who met the inclusion criteria. A retrospective analysis of the clinicopathological characteristics of NF-pNEN patients was conducted. Kaplan-Meier method was used to calculate the survival time. A multivariate Cox regression model was used to analyze the survival outcomes and risk factors. Results From 2000 to 2017, the SEER database registered 10576 patients with pNENs and 1774 patients with liver metastases. Cox analysis revealed that age, sex, primary site, grade, tumor stage, surgery, tumor size, and liver metastasis were risk factors of prognosis, with grade being the most influential index. Patients with NF-pNENs with liver metastasis and no metastasis had different primary site, grade, and tumor size. In general, a higher grade was associated with a larger tumor and a greater risk of liver metastasis. Meanwhile, patients with liver metastasis showed that those with tumors originated from the tail of the pancreas had better prognoses than those with tumors originated from other parts. Surgical treatment can improve the prognosis of patients with liver metastases, despite the tumor grade. Conclusions The incidence of pNENs has been increasing annually, and the liver has been the most common site of metastasis. Liver metastasis in patients with NF-pNENs, related to tumor size and grade, affected their long-term survival. Surgery significantly improved the prognosis of patients with liver metastases secondary to NF-pNENs with different grades.
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Kaliszewski K, Ludwig M, Greniuk M, Mikuła A, Zagórski K, Rudnicki J. Advances in the Diagnosis and Therapeutic Management of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs). Cancers (Basel) 2022; 14:2028. [PMID: 35454934 PMCID: PMC9030061 DOI: 10.3390/cancers14082028] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 04/10/2022] [Accepted: 04/14/2022] [Indexed: 02/07/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are an increasingly common cause of neoplastic diseases. One of the largest groups of NENs are neoplasms localized to the gastroenteropancreatic system, which are known as gastroenteropancreatic NENs (GEP-NENs). Because of nonspecific clinical symptoms, GEP-NEN patient diagnosis and, consequently, their treatment, might be difficult and delayed. This situation has forced researchers all over the world to continue progress in the diagnosis and treatment of patients with GEP-NENs. Our review is designed to present the latest reports on the laboratory diagnostic techniques, imaging tests and surgical and nonsurgical treatment strategies used for patients with these rare neoplasms. We paid particular attention to the nuclear approach, the use of which has been applied to GEP-NEN patient diagnosis, and to nonsurgical and radionuclide treatment strategies. Recent publications were reviewed in search of reports on new strategies for effective disease management. Attention was also paid to those studies still in progress, but with successful results. A total of 248 papers were analyzed, from which 141 papers most relevant to the aim of the study were selected. Using these papers, we highlight the progress in the development of diagnostic and treatment strategies for patients with GEP-NENs.
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Affiliation(s)
- Krzysztof Kaliszewski
- Department of General, Minimally Invasive and Endocrine Surgery, Wroclaw Medical University, Borowska Street 213, 50-556 Wroclaw, Poland; (M.L.); (M.G.); (A.M.); (K.Z.); (J.R.)
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[Diagnostics and clinical management of premalignant diseases of the pancreas]. Internist (Berl) 2022; 63:401-413. [PMID: 35234978 DOI: 10.1007/s00108-022-01308-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2022] [Indexed: 10/19/2022]
Abstract
Pancreatic cancer is one of the most aggressive solid tumors and still has a poor prognosis. A delayed diagnosis at advanced stages and a poor response to systemic treatment frequently make a curative treatment impossible. Therefore, the identification of high-risk patients and screening them regularly is the most promising approach to improve the prognosis. Chronic pancreatitis as well as neoplastic pancreatic cysts can greatly increase the risk of developing pancreatic cancer. Furthermore, familial syndromes and germline mutations also confer an increased risk for development of pancreatic cancer. This article provides an overview of the various premalignant diseases of the pancreas. The value of the various imaging modalities, such as magnetic resonance imaging and endosonography are particularly discussed as well as the screening interval and the indications for surgical treatment are explained.
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Hashimoto S, Nakaoka K, Tanaka H, Kuzuya T, Kawabe N, Nagasaka M, Nakagawa Y, Miyahara R, Shibata T, Hirooka Y. Transabdominal ultrasonographic diagnosis of relatively rare pancreatic neoplasms. J Med Ultrason (2001) 2022; 49:187-197. [PMID: 35149959 DOI: 10.1007/s10396-022-01192-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 01/12/2022] [Indexed: 11/28/2022]
Abstract
There are various types of pancreatic neoplasms, and their prognosis and treatment methods are different. Therefore, accurate diagnosis is important to determine the best treatment strategy. Transabdominal ultrasonography is frequently used as a screening examination for diagnostic imaging of pancreatic neoplasms. In this review, we have focused on the characteristics of ultrasonic findings for relatively rare pancreatic neoplasms.
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Affiliation(s)
- Senju Hashimoto
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Kazunori Nakaoka
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Hiroyuki Tanaka
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Naoto Kawabe
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Mitsuo Nagasaka
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Yoshihito Nakagawa
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Ryoji Miyahara
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Tomoyuki Shibata
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Hepatology, Fujita Health University School of Medicine, 1‑98 Dengakugakubo, Kutukake‑cho, Toyoake, Aichi, 470‑1192, Japan.
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How to Select Patients Affected by Neuroendocrine Neoplasms for Surgery. Curr Oncol Rep 2022; 24:227-239. [PMID: 35076884 DOI: 10.1007/s11912-022-01200-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2021] [Indexed: 11/03/2022]
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Marchese U, Gaillard M, Pellat A, Tzedakis S, Abou Ali E, Dohan A, Barat M, Soyer P, Fuks D, Coriat R. Multimodal Management of Grade 1 and 2 Pancreatic Neuroendocrine Tumors. Cancers (Basel) 2022; 14:433. [PMID: 35053593 PMCID: PMC8773540 DOI: 10.3390/cancers14020433] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/11/2022] [Accepted: 01/13/2022] [Indexed: 12/13/2022] Open
Abstract
Pancreatic neuroendocrine tumors (p-NETs) are rare tumors with a recent growing incidence. In the 2017 WHO classification, p-NETs are classified into well-differentiated (i.e., p-NETs grade 1 to 3) and poorly differentiated neuroendocrine carcinomas (i.e., p-NECs). P-NETs G1 and G2 are often non-functioning tumors, of which the prognosis depends on the metastatic status. In the localized setting, p-NETs should be surgically managed, as no benefit for adjuvant chemotherapy has been demonstrated. Parenchymal sparing resection, including both duodenum and pancreas, are safe procedures in selected patients with reduced endocrine and exocrine long-term dysfunction. When the p-NET is benign or borderline malignant, this surgical option is associated with low rates of severe postoperative morbidity and in-hospital mortality. This narrative review offers comments, tips, and tricks from reviewing the available literature on these different options in order to clarify their indications. We also sum up the overall current data on p-NETs G1 and G2 management.
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Affiliation(s)
- Ugo Marchese
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Martin Gaillard
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Anna Pellat
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
| | - Stylianos Tzedakis
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Einas Abou Ali
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
| | - Anthony Dohan
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - Maxime Barat
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - Philippe Soyer
- Department of Radiology, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.D.); (M.B.); (P.S.)
| | - David Fuks
- Department of Digestive, Hepatobiliary and Pancreatic Surgery, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (M.G.); (S.T.); (D.F.)
| | - Romain Coriat
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, AP-HP, Université de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France; (A.P.); (E.A.A.); (R.C.)
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Tan Q, Wang X, Li Y, Liu Y, Liu X, Ke N. Prognostic Factors of Small Non-Functional Pancreatic Neuroendocrine Tumors and the Risk of Lymph Node Metastasis: A Population-Level Study. Front Endocrinol (Lausanne) 2022; 13:907415. [PMID: 35873006 PMCID: PMC9299363 DOI: 10.3389/fendo.2022.907415] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 05/04/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Small non-functional neuroendocrine tumors (NF-PNETs) are a heterogeneous subset of tumors with controversy regarding their optimal management. We aimed to analyze the prognostic factors of patients with small NF-PNETs and create a risk score for lymph node metastasis (LNM). METHODS Data of 751 patients with NF-PNETs ≤ 2 cm were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate survival analysis was performed to analyze the prognostic factors. Logistic regression was used to identify risk factors for LNM. RESULTS Of the 751 patients, 99 (13.2%) were confirmed to have LNM. In multivariate survival analysis, LNM (hazard ratio [HR], 2.12; 95% CI, 1.04-4.32, p = 0.040) was independently associated with disease-specific survival. Logistic regression identified that tumor location in the head of the pancreas (odds ratio [OR], 4.33; 95% CI, 2.75-6.81; p < 0.001), size ≥ 1.5-2 cm (OR, 1.84; 95% CI, 1.17-2.87; p = 0.009), and grade III-IV (OR, 7.90; 95% CI, 1.79-34.90; p = 0.006) were independent risk factors of LNM. According to the OR value, the risk of LNM was scored as follows: a score of 1 for tumors located in the body/tail of the pancreas and 4 for those located in the head; a score of 1 for tumors <1 cm and 2 for those ≥1.5-2 cm; and a score of 1 for tumors with grade I-II and 8 for those with grade III-IV. Finally, the median score for this cohort was 4, with an interquartile range of 3-6. Therefore, patients were classified as three groups based on the risk score system: a total score of 1-3 for low risk, 4-6 for intermediate risk (OR, 2.98; 95% CI, 1.59-5.60; p = 0.001), and 7-14 for high risk (OR, 8.94; 95% CI, 4.50-17.7; p < 0.001), with an incidence of LNM 5.0%, 13.5%, and 31.8%, respectively (p < 0.001). CONCLUSION Surgical resection with regional lymphadenectomy is recommended for small NF-PNETs with malignant potential of LNM. A risk score for LNM based on tumor grade, location, and size may preoperatively predict LNM of small NF-PNETs and guide clinical practice.
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Affiliation(s)
- Qingquan Tan
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xing Wang
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yichen Li
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yingyi Liu
- The First Clinical College, Chongqing Medical University, Chongqing, China
| | - Xubao Liu
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xubao Liu, ; Nengwen Ke,
| | - Nengwen Ke
- Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Xubao Liu, ; Nengwen Ke,
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Yang Z, Zhang D, Shi G. Reappraisal of a 2-cm Cutoff Size for the Management of Nonfunctional Pancreatic Neuroendocrine Tumors: A Population-Based Study. Front Endocrinol (Lausanne) 2022; 13:928341. [PMID: 35923628 PMCID: PMC9339804 DOI: 10.3389/fendo.2022.928341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 05/31/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Expectant observation and aggressive surgery are both recommended for small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs). However, the optimal management of small NF-PanNETs remains disputable due to the heterogeneous clinical behavior. METHODS Patients who were diagnosed with pancreatic neuroendocrine neoplasms (PanNENs) between 2000 and 2018 were identified from the surveillance, epidemiology, and end results (SEER) database and reviewed retrospectively. Tumor aggressiveness was defined as poor differentiation, lymph node involvement, liver involvement, and advanced stage. The best cutoff of tumor size associated with tumor aggressiveness was determined through the receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to identify prognostic factors in patients with tumors of ≤2 cm. RESULTS A total of 5,172 patients with PanNENs were enrolled, including 1,760 (34.0%) tumors ≤2 cm and 3,412 (66.0%) tumors >2 cm. A 2.5-cm cutoff size was found to be associated with a satisfactory ability in predicting tumor aggressiveness. On multivariate analysis, age, gender, ethnicity, tumor grade, tumor number, and stage were independent prognostic factors for overall survival (OS) in patients with tumors less than or equal to 2 cm in size. A total of 1,621 patients were diagnosed with NF-PanNETs according to the WHO classification, of whom 1,350 underwent surgery, 271 performed active observation. The OS was significantly better in the surgery group compared to the observation group regardless of propensity score analysis. Additionally, a total of 407 patients were selected based on the multivariate Cox regression analysis, of whom 46 underwent observation, 361 underwent surgery, and the OS was comparable. CONCLUSION Expectant observation may be a reasonable alternative to aggressive surgical resection in highly selected small NF-PanNET patients. Also, the decision to observe versus surgery should not only be based on tumor size alone but also take into account other important clinicopathological factors.
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Paiella S, Landoni L, Tebaldi S, Zuffante M, Salgarello M, Cingarlini S, D'Onofrio M, Parisi A, Deiro G, Manfrin E, Bianchi B, Montagnini G, Crinò SF, Bassi C, Salvia R. Dual-Tracer (68Ga-DOTATOC and 18F-FDG-)-PET/CT Scan and G1-G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Single-Center Retrospective Evaluation of 124 Nonmetastatic Resected Cases. Neuroendocrinology 2022; 112:143-152. [PMID: 33508821 DOI: 10.1159/000514809] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 01/28/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The combined use of 68gallium (68Ga)-DOTA-peptides and 18fluorine-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) scans in the workup of pancreatic neuroendocrine tumors (PanNETs) is controversial. This study aimed at assessing both tracers' capability to identify tumors and to assess its association with pathological predictors of recurrence. METHODS Prospectively collected, preoperative, dual-tracer PET/CT scan data of G1-G2, nonmetastatic, PanNETs that underwent surgery between January 2013 and October 2019 were retrospectively analyzed. RESULTS The final cohort consisted of 124 cases. There was an approximately equal distribution of males and females (50.8%/49.2%) and G1 and G2 tumors (49.2%/50.8%). The disease was detected in 122 (98.4%) and 64 (51.6%) cases by 68Ga-DOTATOC and by 18F-FDG PET/CT scans, respectively, with a combined sensitivity of 99.2%. 18F-FDG-positive examinations found G2 tumors more often than G1 (59.4 vs. 40.6%; p = 0.036), and 18F-FDG-positive PanNETs were larger than negative ones (median tumor size 32 mm, interquartile range [IQR] 21 vs. 26 mm, IQR 20; p = 0.019). The median Ki67 for 18F-FDG-positive and -negative examinations was 3 (IQR 4) and 2 (IQR 4), respectively (p = 0.029). At least 1 pathological predictor of recurrence was present in 74.6% of 18F-FDG-positive cases (vs. 56.7%; p = 0.039), whereas this was not found when dichotomizing the PanNETs by their dimensions (≤/>20 mm). None of the 2 tracers predicted nodal metastasis. The receiver operating characteristic curve analysis showed that 18F-FDG uptake higher than 4.2 had a sensitivity of 49.2% and specificity of 73.3% for differentiating G1 from G2 (AUC = 0.624, p = 0.009). CONCLUSION The complementary adoption of 68Ga-DOTATOC and 18F-FDG tracers may be valuable in the diagnostic workup of PanNETs despite not being a game-changer for the management of PanNETs ≤20 mm.
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Affiliation(s)
- Salvatore Paiella
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Luca Landoni
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Sarah Tebaldi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Michele Zuffante
- Nuclear Medicine Unit, Integrated University Hospital of Verona, Verona, Italy
| | - Matteo Salgarello
- Department of Nuclear Medicine, Ospedale Sacro Cuore Don Calabria, Negrar, Verona, Italy
| | - Sara Cingarlini
- Pancreas Institute, Oncology Unit, University of Verona Hospital Trust, Verona, Italy
| | - Mirko D'Onofrio
- Pancreas Institute, Radiology Unit, University of Verona Hospital Trust, Verona, Italy
| | - Alice Parisi
- Pancreas Institute, Department of Diagnostics and Public Health, Section of Pathology, University Verona Hospital Trust, Verona, Italy
| | - Giacomo Deiro
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Erminia Manfrin
- Pancreas Institute, Department of Diagnostics and Public Health, Section of Pathology, University Verona Hospital Trust, Verona, Italy
| | - Beatrice Bianchi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Greta Montagnini
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Stefano Francesco Crinò
- Pancreas Institute, Gastroenterology and Digestive Endoscopy Unit, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Pancreas Institute, General and Pancreatic Surgery Unit, University of Verona Hospital Trust, Verona, Italy
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Gamal GH. The utility of 18F-FDG PET/CT in the diagnosis, staging of non-functioning pancreatic neuroendocrine tumors. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2021. [DOI: 10.1186/s43055-021-00617-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
The non-functional PNETs are often discovered incidentally, they are commonly malignant and commonly present at a late stage with large size. We evaluate in this study the usefulness of 18F-FDG PET/CT in the detection and staging of non-functioning PNETs.
Results
Thirty patients with non-functioning PNETs were involved in this prospective study over a period starting from September 2016 to March 2021. Age ranged from 33 to 79 years. 18F-FDG PET/CT detected 26 patients had SUV max ≥ 2.5 of primary lesions and 4 lesions had SUV max < 2.5. There was no statistical significant between the site of the lesions and the type of grading of the tumors. 32 distant metastatic lesions were detected which show SUVmax ≥ 2.5 and only 9%where below 2.5. Of 30 patients, 4 patients (13.3%) of well differentiated tumor had altered their clinical strategies according to the results of PET/CT examinations. 18F-FDG PET/CT upstaged 1 patient with stage IB and 3 patients with IIA and B to stage IV.
Conclusion
The increased use of 18F-FDG PET/CT in the investigation of patient with PNETs allows for more accurate staging and therefore more appropriate management decision.
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de Ponthaud C, Menegaux F, Gaujoux S. Updated Principles of Surgical Management of Pancreatic Neuroendocrine Tumours (pNETs): What Every Surgeon Needs to Know. Cancers (Basel) 2021; 13:5969. [PMID: 34885079 PMCID: PMC8656761 DOI: 10.3390/cancers13235969] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 11/25/2021] [Accepted: 11/25/2021] [Indexed: 02/07/2023] Open
Abstract
Pancreatic neuroendocrine tumours (pNETs) represent 1 to 2% of all pancreatic neoplasm with an increasing incidence. They have a varied clinical, biological and radiological presentation, depending on whether they are sporadic or genetic in origin, whether they are functional or non-functional, and whether there is a single or multiple lesions. These pNETs are often diagnosed at an advanced stage with locoregional lymph nodes invasion or distant metastases. In most cases, the gold standard curative treatment is surgical resection of the pancreatic tumour, but the postoperative complications and functional consequences are not negligible. Thus, these patients should be managed in specialised high-volume centres with multidisciplinary discussion involving surgeons, oncologists, radiologists and pathologists. Innovative managements such as "watch and wait" strategies, parenchymal sparing surgery and minimally invasive approach are emerging. The correct use of all these therapeutic options requires a good selection of patients but also a constant update of knowledge. The aim of this work is to update the surgical management of pNETs and to highlight key elements in view of the recent literature.
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Affiliation(s)
- Charles de Ponthaud
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
| | - Fabrice Menegaux
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
| | - Sébastien Gaujoux
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France; (C.d.P.); (F.M.)
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Bat. Husson Mourier, 47-83 Boulevard de l’Hôpital, 75013 Paris, France
- Paris-Sorbonne University, 21 rue de l’Ecole de Médecine, 75006 Paris, France
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Frey S, Mirallié E, Le Bras M, Regenet N. What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review. Cancers (Basel) 2021; 13:5954. [PMID: 34885063 PMCID: PMC8656750 DOI: 10.3390/cancers13235954] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are a heterogeneous group of tumors derived from cells with neuroendocrine differentiation. They are considered malignant by default. However, their outcomes are variable depending on their presentation in the onset of hereditary syndromes, hormonal secretion, grading, and extension. Therefore, although surgical treatment has long been suggested as the only treatment of pancreatic neuroendocrine neoplasms, its modalities are an evolving landscape. For selected patients (small, localized, non-functional panNENs), a "wait and see" strategy is suggested, as it is in the setting of multiple neuroendocrine neoplasia type 1, but the accurate size cut-off remains to be established. Parenchyma-sparring pancreatectomy, aiming to limit pancreatic insufficiency, are also emerging procedures, which place beyond the treatment of insulinomas and small non-functional panNENs (in association with lymph node picking) remains to be clarified. Furthermore, giving the fact that the liver is generally the only metastatic site, surgery keeps a place of choice alongside medical therapies in the treatment of metastatic disease, but its modalities and extensions are still a matter of debate. This narrative review aims to describe the current recommended surgical management for pancreatic NENs and controversies in light of the actual recommendations and recent literature.
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Affiliation(s)
- Samuel Frey
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- L’institut du Thorax, Université de Nantes, CNRS, INSERM, CHU de Nantes, 44000 Nantes, France
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Eric Mirallié
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Maëlle Le Bras
- Endocrinologie, Diabétologie et Nutrition, L’institut du Thorax, CHU Nantes, 44000 Nantes, France;
| | - Nicolas Regenet
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
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Cienfuegos JA, Hurtado-Pardo L, Rotellar F. Small pancreatic neuroendocrine tumours: observe and monitor or prompt surgical resection. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 114:1-4. [PMID: 34794318 DOI: 10.17235/reed.2021.8419/2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Over recent decades there has been a significant increase in the annual incidence of neuroendocrine tumors of the pancreas (PanNets), from 0.4 to 0.8 per 100,000 inhabitants, due to the more widespread use of more sensitive imaging techniques (cross-sectional and functional imaging).
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Tsilimigras DI, Pawlik TM. Pancreatic neuroendocrine tumours: conservative versus surgical management. Br J Surg 2021; 108:1267-1269. [PMID: 34519788 DOI: 10.1093/bjs/znab232] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 06/02/2021] [Indexed: 11/12/2022]
Affiliation(s)
- D I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - T M Pawlik
- Department of Surgery, Division of Surgical Oncology, Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA
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Incidence, Clinical Presentation and Trends in Indication for Diagnostic Work-Up of Small Intestinal and Pancreatic Neuroendocrine Tumors. Diagnostics (Basel) 2021; 11:diagnostics11112030. [PMID: 34829377 PMCID: PMC8624499 DOI: 10.3390/diagnostics11112030] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 10/26/2021] [Accepted: 10/28/2021] [Indexed: 01/15/2023] Open
Abstract
Background: The incidence of small intestinal (SI) and pancreatic neuroendocrine tumors (siNETs and pNETs) seems to have increased. The increased frequency of incidental findings might be a possible explanation. The study aimed to examine (1) changes in incidence and the stage at diagnosis (2010–2011 vs. 2019–2020), (2) changes in the initial indication for diagnostic workup and 3) the differences in stage between incidentally discovered vs. symptomatic disease during the entire study period. Methods: We performed a retrospective study, that includes consecutive siNET and pNET patients referred to the Copenhagen ENETS center of excellence in 2010–2011 and 2019–2020. Results: The annual incidence of siNET per 100,000 increased from 1.39 to 1.84, (p = 0.05). There was no change in the stage at diagnosis, and in both periods approximately 30% of patients were incidentally diagnosed (p = 0.62). Dissemination was found in 72/121 (60%) of symptomatic vs. 22/50 (44%) of incidentally discovered SI tumors in the entire cohort, (p = 0.06). The annual incidence of pNET increased from 0.42 to 1.39 per 100,000, (p < 0.001). The proportion of patients with disseminated disease decreased from 8/21 (38%) to 12/75 (16%), (p = 0.02) and the number of incidental findings increased from 4/21 (19%) to 43/75 (57%), (p = 0.002). More symptomatic patients had disseminated disease compared to patients with incidentally discovered tumors (15/49 (31%) vs. 5/47 (11%), (p = 0.01)). Conclusion: The incidence of siNET and pNETs increased over the past decade. For siNETs, the stage of disease and the distribution of symptomatic vs. incidentally discovered tumors were unchanged between the two periods. Patients with pNETs presented with more local and incidentally discovered tumors in the latter period. Patients with incidentally discovered siNETs had disseminated disease in 44% of the overall cases. The vast majority of incidentally found pNETs were localized.
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Frequency of Neuroendocrine Tumor Studies: Using Latent Dirichlet Allocation and HJ-Biplot Statistical Methods. MATHEMATICS 2021. [DOI: 10.3390/math9182281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background: Neuroendocrine tumors (NETs) are severe and relatively rare and may affect any organ of the human body. The prevalence of NETs has increased in recent years; however, there seem to be more data on particular types, even though, despite the efforts of different guidelines, there is no consensus on how to identify different types of NETs. In this review, we investigated the countries that published the most articles about NETs, the most frequent organs affected, and the most common related topics. Methods: This work used the Latent Dirichlet Allocation (LDA) method to identify and interpret scientific information in relation to the categories in a set of documents. The HJ-Biplot method was also used to determine the relationship between the analyzed topics, by taking into consideration the years under study. Results: In this study, a literature review was conducted, from which a total of 7658 abstracts of scientific articles published between 1981 and 2020 were extracted. The United States, Germany, United Kingdom, France, and Italy published the majority of studies on NETs, of which pancreatic tumors were the most studied. The five most frequent topics were t_21 (clinical benefit), t_11 (pancreatic neuroendocrine tumors), t_13 (patients one year after treatment), t_17 (prognosis of survival before and after resection), and t_3 (markers for carcinomas). Finally, the results were put through a two-way multivariate analysis (HJ-Biplot), which generated a new interpretation: we grouped topics by year and discovered which NETs were the most relevant for which years. Conclusions: The most frequent topics found in our review highlighted the severity of NETs: patients have a poor prognosis of survival and a high probability of tumor recurrence.
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