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Clarke CN, Ward E, Henry V, Nimmer K, Phan A, Evans DB. Impact of Regional Metastasis on Survival for Patients with Nonfunctional Pancreatic Neuroendocrine Tumors: A Systematic Review. Ann Surg Oncol 2024; 31:4976-4985. [PMID: 38652199 DOI: 10.1245/s10434-024-15249-1] [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: 08/31/2023] [Accepted: 03/19/2024] [Indexed: 04/25/2024]
Abstract
BACKGROUND Controversy exists regarding the benefit of lymphadenectomy for nonfunctional pancreatic neuroendocrine tumors (NF-PNET). PATIENTS AND METHODS MEDLINE/PubMed, EMBASE, and the Cochrane Library were searched for studies of pancreatic neuroendocrine tumors (PNET) published between 1990 and 2021. Studies of functional PNET were excluded. Reported incidence of lymph node metastasis (LNM) and survival analysis of either disease-free survival (DFS) or overall survival (OS) were required for inclusion. RESULTS Overall, 52 studies analyzing 24,608 PNET met the inclusion criteria. The reported LNM rate for NF-PNET ranged from 7 to 64 % (median 24.5%). Reported LNM rates ranged from 7 to 51% (median 11%) for NF-PNET< 2 cm in 14 studies and 29-47% (median 38%) in NF-PNET > 2 cm. In total, 19 studies (66%) reported LNM to have a negative impact on DFS. Additionally, 21 studies (60%) reported LNM to have a negative impact on OS. Two studies investigating the impact of lymphadenectomy (LND) found LND had the greatest impact for large, high-grade tumors. The overall quality of available evidence was low as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation System. CONCLUSIONS Published literature evaluating the impact of regional LNM and LND in PNET is confounded by heterogeneity in practice patterns and the retrospective nature of these cohort studies. Most studies suggest high rates of LNM in NF-PNET that negatively impact DFS and OS. Given the high rate of LNM in NF-PNET and its potential detrimental effect on DFS and OS, we recommend lymphadenectomy be completed for NF-PNET > 2 cm and strongly considered for NF-PNET < 2 cm.
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Affiliation(s)
- Callisia N Clarke
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
| | - Erin Ward
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Valencia Henry
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Kaitlyn Nimmer
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Alexandria Phan
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Doug B Evans
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
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Hesami M, Blake M, Anderson MA, Asmundo L, Kilcoyne A, Najmi Z, Caravan PD, Catana C, Czawlytko C, Esfahani SA, Kambadakone AR, Samir A, McDermott S, Domachevsky L, Ursprung S, Catalano OA. Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses. J Comput Assist Tomogr 2024; 48:521-532. [PMID: 38657156 PMCID: PMC11245376 DOI: 10.1097/rct.0000000000001615] [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] [Indexed: 04/26/2024]
Abstract
ABSTRACT Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.
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Affiliation(s)
- Mina Hesami
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Michael Blake
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Mark A. Anderson
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Luigi Asmundo
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
- Postgraduation School in Radiodiagnostics, Università degli Studi di Milano, Milan, Italy
| | - Aoife Kilcoyne
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Zahra Najmi
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Peter D. Caravan
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ciprian Catana
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Cynthia Czawlytko
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shadi Abdar Esfahani
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Avinash R. Kambadakone
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Anthony Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shaunagh McDermott
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Liran Domachevsky
- Department of Nuclear Medicine, The Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Stephan Ursprung
- Department of Radiology, University Hospital Tuebingen, Tuebingen, Germany
| | - Onofrio A. Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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Asmundo L, Rizzetto F, Blake M, Anderson M, Mojtahed A, Bradley W, Shenoy-Bhangle A, Fernandez-del Castillo C, Qadan M, Ferrone C, Clark J, Ambrosini V, Picchio M, Mapelli P, Evangelista L, Leithner D, Nikolaou K, Ursprung S, Fanti S, Vanzulli A, Catalano OA. Advancements in Neuroendocrine Neoplasms: Imaging and Future Frontiers. J Clin Med 2024; 13:3281. [PMID: 38892992 PMCID: PMC11172657 DOI: 10.3390/jcm13113281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 05/23/2024] [Accepted: 05/30/2024] [Indexed: 06/21/2024] Open
Abstract
Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management.
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Affiliation(s)
- Luigi Asmundo
- Postgraduation School in Radiodiagnostics, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy;
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Francesco Rizzetto
- Postgraduation School in Radiodiagnostics, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy;
- Department of Radiology, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy;
| | - Michael Blake
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Mark Anderson
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Amirkasra Mojtahed
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - William Bradley
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Anuradha Shenoy-Bhangle
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
| | - Carlos Fernandez-del Castillo
- Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (C.F.-d.C.); (M.Q.)
| | - Motaz Qadan
- Department of Surgery, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (C.F.-d.C.); (M.Q.)
| | - Cristina Ferrone
- Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA;
| | - Jeffrey Clark
- Department of Oncology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA;
| | - Valentina Ambrosini
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (V.A.); (S.F.)
- Nuclear Medicine, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Maria Picchio
- Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy; (M.P.); (P.M.)
| | - Paola Mapelli
- Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132 Milan, Italy; (M.P.); (P.M.)
| | - Laura Evangelista
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy;
| | - Doris Leithner
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany;
| | - Konstantin Nikolaou
- Department of Radiology, University Hospital Tuebingen, Osianderstraße 5, 72076 Tübingen, Germany; (K.N.); (S.U.)
| | - Stephan Ursprung
- Department of Radiology, University Hospital Tuebingen, Osianderstraße 5, 72076 Tübingen, Germany; (K.N.); (S.U.)
| | - Stefano Fanti
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 9, 40138 Bologna, Italy; (V.A.); (S.F.)
- Nuclear Medicine, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Angelo Vanzulli
- Department of Radiology, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy;
- Department of Oncology and Hemato-Oncology, Università Degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy
| | - Onofrio Antonio Catalano
- Department of Radiology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA; (M.B.); (M.A.); (A.M.); (W.B.); (A.S.-B.)
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Mestre-Alagarda C, Srirajaskanthan R, Zen Y, Giwa M, Howard M, Ooft ML. Genetic and epigenetic prognosticators of neuroendocrine tumours of the GI tract, liver, biliary tract and pancreas: A systematic review and meta-analysis. Histopathology 2024; 84:255-265. [PMID: 37565289 DOI: 10.1111/his.15025] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 07/25/2023] [Accepted: 07/30/2023] [Indexed: 08/12/2023]
Abstract
Multiple recurrent genetic and epigenetic aberrations have been associated with worse prognosis in multiple studies of neuroendocrine tumours (NETs), but these have been mainly small cohorts and univariate analysis. This review and meta-analysis will focus upon the literature available on NETs of the gastrointestinal (GI) tract, liver, biliary tract and pancreas. PubMed and Embase were searched for publications that investigated the prognostic value of (epi)genetic changes of neuroendocrine tumours. A meta-analysis was performed assessing the association of the (epi)genetic alterations with overall survival (OS), disease-free survival (DFS) or locoregional control (LRC). In the pancreas DAXX/ATRX [hazard ratio (HR) = 3.29; 95% confidence interval (CI) = 2.28-4.74] and alternative lengthening telomeres (ALT) activation (HR = 8.20; 95% CI = 1.40-48.07) showed a pooled worse survival. In the small bowel NETs gains on chromosome 14 were associated with worse survival (HR 2.85; 95% CI = 1.40-5.81). NETs from different anatomical locations must be regarded as different biological entities with diverging molecular prognosticators, and epigenetic changes being important to the pathogenesis of these tumours. This review underpins the prognostic drivers of pancreatic NET which lie in mutations of DAXX/ATRX and ALT pathways. However, there is reaffirmation that prognostic molecular biomarkers of small bowel NETs should be sought in copy number variations (CNVs) rather than in single nucleotide variations (SNVs). This review also reveals how little is known about the prognostic significance of epigenetics in NETs.
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Affiliation(s)
| | | | - Yoh Zen
- Institute of Liver Studies, King's College Hospital and King's College London, London, UK
| | - Mojisola Giwa
- Department of Histopathology, King's College Hospital, King's College, London, UK
| | - Mark Howard
- Department of Histopathology, King's College Hospital, King's College, London, UK
| | - Marc Lucas Ooft
- Institute of Liver Studies, King's College Hospital, London, UK
- Pathology-DNA, Rijnstate Hospital, Arnhem, the Netherlands
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Lu Z, Li T, Liu C, Zheng Y, Song J. Development and validation of a survival prediction model and risk stratification for pancreatic neuroendocrine neoplasms. J Endocrinol Invest 2023; 46:927-937. [PMID: 36394822 DOI: 10.1007/s40618-022-01956-7] [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: 09/03/2022] [Accepted: 10/30/2022] [Indexed: 11/18/2022]
Abstract
PURPOSE We explored risk variables associated with cancer-specific survival (CSS) in patients with pancreatic neuroendocrine neoplasms (PNENs) and created a network dynamic nomogram model to predict patient survival time. METHODS A total of 7750 patients with PNENs were included in this analysis, including 134 with functional PNENs and 7616 with nonfunctional PNENs. Clinical feature and prognosis differences between functional and nonfunctional PNENs were compared. Independent prognostic factors affecting CSS were analyzed by univariate and multifactorial Cox regression. Nomogram and web-based prognosis prediction of PNENs were developed and validated by C indices, decision curve analysis, and calibration plots. RESULTS Patients with functional PNENs were younger at diagnosis than those with nonfunctional PNENs. Functional PNENs had better prognoses than nonfunctional PNENs (5-year survival rates: 78.55% and 71.10%, respectively). Univariate and multifactorial Cox regression analyses showed that tumor infiltration (T), nodal metastasis (N), metastasis (M), tumor site, differentiation grade, age, marital status, and surgical treatment were independent prognostic risk factors for CSS, which were included in the prognostic nomogram and web-based prognosis calculator. The calibration plots and decision curve analysis showed that the nomogram had excellent prediction and clinical practical ability. The C indices for CSS in the training and validation cohorts were 0.848 (95% CI 0.838-0.8578) and 0.823 (95% CI 0.807-0.839), respectively. We scored all patients according to the nomogram and divided patients into three different risk groups. The prognosis of the low-risk population was significantly better than those of the middle- and high-risk populations based on Kaplan-Meier survival curve. CONCLUSION We analyzed the clinical features of PNENs and developed a convenient and web dynamic nomogram to predict CSS.
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Affiliation(s)
- Z Lu
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, NO. 1 DaHua Road, Dong Dan, Beijing, 100730, People's Republic of China
| | - T Li
- National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Dahua Road, Dongcheng District, Beijing, 100730, People's Republic of China
- Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - C Liu
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, NO. 1 DaHua Road, Dong Dan, Beijing, 100730, People's Republic of China
| | - Y Zheng
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, NO. 1 DaHua Road, Dong Dan, Beijing, 100730, People's Republic of China
- Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - J Song
- Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, NO. 1 DaHua Road, Dong Dan, Beijing, 100730, People's Republic of China.
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Kaur A, Wang S, Herbert J, Steinberg L, Kumar A. Analysis of Clinical Characteristics and Survival in Patients With Functional Neuroendocrine Tumors of Gastrointestinal Origin. Pancreas 2022; 51:1171-1178. [PMID: 37078942 DOI: 10.1097/mpa.0000000000002171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/21/2023]
Abstract
OBJECTIVES Functional neuroendocrine tumors (FNETs) are characterized by excess secretion of disease-specific hormones. In this study, we attempted to define survival trends in patients with some of these uncommon tumors. METHODS Using the Surveillance, Epidemiology, and End Results database, 529 patients with FNETs (gastrinoma, insulinoma, glucagonoma, VIPoma, and somatostatinoma) were identified. We analyzed patient and tumor characteristics, overall survival, and cancer-specific survival. RESULTS Functional neuroendocrine tumors were found to be more predominant in White patients older than 50 years. Most common FNETs were gastrinoma (56.3%) and insulinoma (23.8%). Most FNETs were found in the pancreas, with the second most common location being the small bowel. Surgery was the primary modality of treatment, used in 55.8% of the cases. Median overall survival was 9.8 years (95% confidence interval [CI], 7.9-11.8) with a median cancer-specific survival of 18.5 years (95% CI, 12.8-24.2). In multivariate analysis, age >50 years (hazard ratio [HR], 2.7; 95% CI, 2.02-3.64), no surgical resection (HR, 1.88; 95% CI, 1.43-2.46), metastasis (HR, 3.0; 95% CI, 2.0-4.5), and poor differentiation were associated with poor survival. Site and histology did not have a significant impact on survival (P = 0.82 and 0.57 respectively). CONCLUSIONS Our study highlights the most important prognostic factors for gastrointestinal FNETs.
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Affiliation(s)
- Anahat Kaur
- From the Department of Hematology-Oncology, Albert Einstein College of Medicine-Jacobi Medical Center
| | - Shuai Wang
- Department of Internal Medicine, Albert Einstein College of Medicine-Jacobi Medical Center
| | - Joshua Herbert
- Department of Internal Medicine, Albert Einstein College of Medicine-Jacobi Medical Center
| | - Lewis Steinberg
- Department of Hematology-Oncology, Jacobi Medical Center, Bronx, NY
| | - Abhishek Kumar
- From the Department of Hematology-Oncology, Albert Einstein College of Medicine-Jacobi Medical Center
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Reassessment of somatostatin receptor SST4 expression in bronchopulmonary and gastroenteropancreatic neuroendocrine neoplasms using the novel rabbit monoclonal anti-human SST4 antibody 7H49L61. Sci Rep 2022; 12:14722. [PMID: 36042228 PMCID: PMC9428033 DOI: 10.1038/s41598-022-19014-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 08/23/2022] [Indexed: 11/11/2022] Open
Abstract
Somatostatin receptors SST1, SST2, and SST5 are overexpressed in neuroendocrine neoplasms (NENs), but little is known about SST4 expression in NENs because of a lack of specific monoclonal antibodies. We recently developed and thoroughly characterised a rabbit monoclonal anti-human SST4 antibody, 7H49L61, and showed that it is well suited for identifying SST4 expression in routine pathology samples. The present study aimed to re-evaluate SST4 expression in a large set of NEN samples using this antibody. For this purpose, we assessed SST4 expression in 722 formalin-fixed, paraffin-embedded NEN samples from 274 patients by immunohistochemistry using the novel antibody 7H49L61. The immunostaining was semiquantitatively evaluated using the 12-point immunoreactivity score (IRS), and the results were correlated with clinicopathological data. SST4 was detected in 39.3% of all NENs, but with a median IRS of 2.0, its expression intensity was negligible overall. In all cases, both cytoplasmic and membraneous staining was observed. SST4 expression was somewhat higher in bronchopulmonary NEN (BP-NEN) than in gastroenteropancreatic NEN (GEP-NEN) but still very low. SST4 expression positively correlated with favourable patient outcomes in BP-NEN but had a positive association with Ki-67 index or tumour grading and a negative interrelationship with overall survival in GEP-NEN. In conclusion, unlike that of other SST subtypes, SST4 expression in both BP-NEN and GEP-NEN is negligible and of no diagnostic or therapeutic relevance.
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Comparative outcomes of pancreatic neuroendocrine neoplasms: A population-based analysis of the SEER database. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2181-2187. [DOI: 10.1016/j.ejso.2022.05.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/07/2022] [Accepted: 05/17/2022] [Indexed: 11/18/2022]
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Krogh S, Grønbæk H, Knudsen AR, Kissmeyer-Nielsen P, Hummelshøj NE, Dam G. Predicting Progression, Recurrence, and Survival in Pancreatic Neuroendocrine Tumors: A Single Center Analysis of 174 Patients. Front Endocrinol (Lausanne) 2022; 13:925632. [PMID: 35837305 PMCID: PMC9273749 DOI: 10.3389/fendo.2022.925632] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 05/24/2022] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION The European Neuroendocrine Tumor Society, ENETS, reports variables of prognostic significance in pancreatic neuroendocrine tumors (PNET). However, studies have short follow-ups, and the optimal treatment remains controversial. We aimed to determine overall survival (OS), progression-free survival (PFS) after conservative treatment, and recurrence-free survival (RFS) after surgery and further to find predictors of aggressive PNET behavior to support treatment decisions. METHODS 174 patients with PNET treated at Aarhus University Hospital from 2011 to 2021 were included in a retrospective cohort study. Patients were divided into surgically resected (SUR, n=91) and medically or conservatively treated (MED, n=83). Variables were tested in univariate and multivariate survival analysis. Median follow-up time was 3.4 years in the MED group and 4.5 years in the SUR group. RESULTS The 5-year OS was 95% and 65% for the SUR and MED groups, respectively. The 5-year RFS in the SUR group was 80% whereas the 5-year PFS in the MED group was 41%. Larger tumor size, Ki67 index, tumor grade, and stage were predictive of shorter OS, RFS, and PFS. Further, chromogranin A was a predictor of OS. Larger tumor size was associated with higher stage and grade. Only 1 of 28 patients with stage 1 disease and size ≤2 cm developed progression on a watch-and-wait strategy during a median follow-up of 36 months. CONCLUSION This study supported the ENETS staging and grading system to be useful to predict OS, PFS, and RFS in PNET. Further, our data support that small, localized, low-grade PNETS can be followed with active surveillance.
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Affiliation(s)
- Sara Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | | | | | | | - Gitte Dam
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
- *Correspondence: Gitte Dam,
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Imaging and implications of tumor thrombus in abdominal malignancies: reviewing the basics. Abdom Radiol (NY) 2020; 45:1057-1068. [PMID: 31696267 DOI: 10.1007/s00261-019-02282-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Extension of tumor tissue within a vein is a recognized prognostic factor in abdominal malignancy because of its influence on tumor staging and selection of therapeutic management. With the advent of newer surgical techniques, and variable treatment strategies, imaging plays a crucial role in categorizing patients according to the tumor resectability and vascular reconstruction techniques during surgery. Understanding the clinical impact of tumor thrombus increases the awareness of the radiologist about the key findings in tumor staging and decision-making of surgical approach. Ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) can be used individually and in combination to accurately assess the tumor thrombus. In our pictorial review, we will discuss the imaging findings and clinical consequences of tumor thrombosis in abdominal malignancies, including hepatocellular carcinoma, pancreatic neuroendocrine tumor, renal cancer, and adrenal cortical carcinoma.
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Blakely AM, Lafaro KJ, Li D, Kessler J, Chang S, Ituarte PHG, Lee B, Singh G. Lymphovascular Invasion Predicts Lymph Node Involvement in Small Pancreatic Neuroendocrine Tumors. Neuroendocrinology 2020; 110:384-392. [PMID: 31401633 DOI: 10.1159/000502581] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 08/08/2019] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Pancreatic neuroendocrine tumors (p-NETS) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for p-NETS ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small p-NETS. METHODS The National Cancer Database was queried for patients with p-NETS ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004-2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity. RESULTS Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LNs were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 vs. 95 months, log-rank p < 0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p < 0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1-2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these 4 factors, 25% were node-positive. CONCLUSIONS Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional LN dissection to fully stage patients with small p-NETS. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.
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Affiliation(s)
- Andrew M Blakely
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Kelly J Lafaro
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Daneng Li
- Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California, USA
| | - Jonathan Kessler
- Department of Diagnostic Radiology, City of Hope National Medical Center, Duarte, California, USA
| | - Sue Chang
- Department of Pathology, City of Hope National Medical Center, Duarte, California, USA
| | - Philip H G Ituarte
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Byrne Lee
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA
| | - Gagandeep Singh
- Department of Surgery, City of Hope National Medical Center, Duarte, California, USA,
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12
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Zhang C, Wu Y, Zhuang H, Li D, Lin Y, Yin Z, Lu X, Hou B, Jian Z. Establishment and validation of an AJCC stage- and histologic grade-based nomogram for pancreatic neuroendocrine tumors after surgical resection. Cancer Manag Res 2019; 11:7345-7352. [PMID: 31496796 PMCID: PMC6689125 DOI: 10.2147/cmar.s200340] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 06/12/2019] [Indexed: 01/30/2023] Open
Abstract
Background Development of an accurate model to predict prognosis for patients with pancreatic neuroendocrine tumors (P-NETs) after surgical resection is urgently needed. Methods In the present study, we conducted Cox proportional hazards regression to identify critical prognostic factors for P-NETs by analyzing data from 2174 patients in the Surveillance, Epidemiology, and End Results (SEER) database. Based on the results of multivariate analysis, a novel nomogram was established. Finally, the novel nomogram for P-NETs was validated in a cohort of 81 patients from a Chinese institute. Results In the multivariate analysis, age, tumor location, American Joint Committee on Cancer (AJCC) stage, histologic grade, lymph node ratio (LNR) and tumor size were independent risk factors for overall survival (OS) in P-NET patients who underwent radical resection. A nomogram consisting of age, sex, AJCC stage and histologic grade was found to have a concordance index (C-index) of 0.79 for OS in the SEER database, which was significantly higher than the C-index based on the AJCC stage, European Neuroendocrine Tumor Society (ENETS) stage or histologic grade alone. In the validation cohort, the C-index based on the nomogram reached 0.78 for OS. We also defined high-risk (total points >13.5 based on the nomogram) and low-risk populations (total points <13.5 based on the nomogram) in the validation cohort. We found that the actual 5-year recurrence rate in the high-risk group was significantly higher than that in the low-risk group (80.8% vs 23.4%, P<0.001). Kaplan-Meier analysis showed that the 5-year recurrence-free survival (RFS) in the low-risk group was significantly higher than that in the high-risk group (P<0.001). Conclusion An AJCC stage- and histologic grade-based model was found to be extremely efficient in predicting survival for patients with P-NETs after surgical resection and deserves further evaluation for future clinical applications.
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Affiliation(s)
- Chuanzhao Zhang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China
| | - Yanxia Wu
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510080, People's Republic of China
| | - Hongkai Zhuang
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China.,Department of Clinical Medicine, Shantou University of Medical College, Shantou 515000, People's Republic of China
| | - Dezhi Li
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China
| | - Ye Lin
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China
| | - Zi Yin
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China
| | - Xin Lu
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China
| | - Baohua Hou
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China
| | - Zhixiang Jian
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People's Republic of China
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Different somatostatin and CXCR4 chemokine receptor expression in gastroenteropancreatic neuroendocrine neoplasms depending on their origin. Sci Rep 2019; 9:4339. [PMID: 30867449 PMCID: PMC6416272 DOI: 10.1038/s41598-019-39607-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 01/28/2019] [Indexed: 12/12/2022] Open
Abstract
Somatostatin receptors (SST), especially SST2A, are known for their overexpression in well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). The chemokine receptor CXCR4, in contrast, is considered to be present mainly in highly proliferative and advanced tumors. However, comprehensive data are still lacking on potential differences in SST or CXCR4 expression pattern in GEP-NEN in dependence on the place of origin. Overall, 412 samples from 165 GEP-NEN patients, comprising both primary tumors (PT) and metastases (MTS), originating from different parts of the gastrointestinal tract or the pancreas were evaluated for SST and CXCR4 expression by means of immunohistochemistry using monoclonal antibodies. SST2A was present in 85% of PT with a high intensity of expression, followed by SST5 (23%), CXCR4 (21%), SST3 (10%), SST1 (9%), and SST4 (4%). PT displayed higher SST2A and chromogranin A (CgA) expression levels than MTS. In both PT and MTS lower SST2A and CgA expression levels were found in tumors originating from the appendix or colon, compared to tumors from other origins. Tumors derived from appendix or colon were associated with significantly worse patient outcomes. Positive correlations were noted between SST2A and CgA as well as between CXCR4 and Ki-67 expression levels. SST2A and CgA negativity of the tumors was significantly associated with poor patient outcomes. All in all, SST2A was the most prominent receptor expressed in the GEP-NEN samples investigated. However, expression levels varied considerably depending on the location of the primary tumor.
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14
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Benetatos N, Hodson J, Marudanayagam R, Sutcliffe RP, Isaac JR, Ayuk J, Shah T, Roberts KJ. Prognostic factors and survival after surgical resection of pancreatic neuroendocrine tumor with validation of established and modified staging systems. Hepatobiliary Pancreat Dis Int 2018; 17:169-175. [PMID: 29576279 DOI: 10.1016/j.hbpd.2018.03.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 01/03/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Pancreatic neuroendocrine tumors (PNETs) display wide heterogeneity with highly variable prognosis. This study aimed to identify variables related to survival after surgical resection of PNET. METHODS A total of 143 patients were identified from a prospectively maintained database. Patient characteristics were analyzed and prognostic factors for overall survival and progression-free survival were evaluated. The WHO, ENETS and AJCC scoring systems were applied to the cohort, and their ability to predict patient outcomes were compared. RESULTS Multivariate analysis found that female gender, lymph node metastases and increasing WHO 2010 grade to be independently associated with reduced overall survival (P < 0.05). Patients requiring multi-visceral resection or debulking surgery found to be associated with shortest survival. ROC analysis found the ENETS and AJCC scoring systems to be similarly predictive of 5-year overall survival. Modified Ki67 significantly improved its accuracy in predicting 5-year overall survival (AUROC: 0.699 vs 0.605; P < 0.01). CONCLUSIONS Multi-visceral or debulking surgery is associated with poor outcomes. There seems to be no significant difference between enucleation and anatomical segmental resection. Available scoring systems have reasonable accuracy in stratifying disease severity, with no system identified as being superior. Prognostic stratification with modified grading systems needs further validation before applied in clinical practice.
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Affiliation(s)
- Nikolaos Benetatos
- The HPB Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, UK
| | - James Hodson
- Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham, UK
| | - Ravi Marudanayagam
- The HPB Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, UK
| | - Robert P Sutcliffe
- The HPB Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, UK
| | - John R Isaac
- The HPB Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, UK
| | - John Ayuk
- Endocrinology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham, UK
| | - Tahir Shah
- Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospital of Birmingham NHS Foundation Trust, Birmingham, UK
| | - Keith J Roberts
- The HPB Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, UK.
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15
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Zhou B, Zhan C, Wu J, Liu J, Zhou J, Zheng S. Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in Surgically Resectable Pancreatic Neuroendocrine Tumors. Med Sci Monit 2017; 23:5574-5588. [PMID: 29168979 PMCID: PMC5709942 DOI: 10.12659/msm.907182] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background The aim of this study was to evaluate the predictive and prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in pancreatic neuroendocrine tumor (PNET) patients undergoing potentially curative resection. Material/Methods A retrospective review of 172 patients with PNETs was conducted. Kaplan-Meier curves and multivariate Cox proportional models were used to calculate overall survival (OS) and disease-free survival (DFS). The predictive performance of the NLR was compared with other inflammation-based scores and conventional stratification systems using receiver operating characteristic (ROC) curve analysis. Results Elevated NLR and PLR were both associated with advanced AJCC stage and high grade. In the univariate analysis, elevated NLR and PLR were both significantly associated with decreased OS and DFS. In the multivariate analysis, the preoperative NLR, but not the PLR, was an independent risk factor for OS (HR=4.471, 95% CI 1.531–13.054, p=0.006) and DFS (HR=2.531, 95% CI 1.202–5.329, p=0.015). The discriminatory capability of the NLR was superior to that of other inflammation-based scores in OS prediction. Furthermore, the predictive range was expanded by incorporating the NLR into the conventional stratification systems, including the AJCC stage and WHO classification systems. Conclusions As an independent prognostic factor, an elevated preoperative NLR is superior to the PLR with respect to predicting clinical outcomes in PNET patients undergoing potentially curative resection. The incorporation of the NLR into the existing conventional stratification systems improved the predictive accuracy.
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Affiliation(s)
- Bo Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Canyang Zhan
- Department of Neonatology, Children's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Jingjing Wu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Jianhua Liu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Jie Zhou
- Department of Pathology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland)
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16
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Wang BP, Tian WJ, Zhang J, Jiang CX, Qu HQ, Zhu M. Nonfunctional pancreatic endocrine tumor in the peripancreatic region in a Chinese patient with multiple endocrine neoplasia type 1. J Int Med Res 2017; 46:908-915. [PMID: 29239255 PMCID: PMC5971513 DOI: 10.1177/0300060517728653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) in patients with multiple endocrine neoplasia type 1 (MEN1), which results from a mutation in the MEN1 gene, are commonly small, multiple tumors located in the pancreatic head and inside the pancreatic parenchyma. We herein describe a 35-year-old woman with bone pain and a 7-year history of a prolactinoma. She was clinically diagnosed with MEN1 based on the presence of the prolactinoma and parathyroid hyperplasia. Abdominal computed tomography revealed a 5-cm mass close to the splenic hilum. This soft tissue tumor, which was located outside the pancreatic parenchyma and the tissue origin of which could not be identified preoperatively, was found to be connected to the pancreatic tail. After resection, histological examination revealed a well-differentiated neuroendocrine tumor of pancreatic origin. Genetic testing revealed a heterozygous transition mutation of guanine to adenine at the coding nucleotide 133 in exon 2 (c.133G>A), resulting in an amino acid substitution of glutamic acid with lysine (E45K) in the MEN1 gene. This patient with MEN1 presented with a clinical condition involving a single non-metastatic NF-pNET located outside the pancreatic parenchyma with a missense mutation in the MEN1 gene, which could easily have been misdiagnosed as an accessory spleen.
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Affiliation(s)
- Bao-Ping Wang
- 1 Department of Endocrinology, Tianjin Medical University General Hospital, Heping District, Tianjin, China
| | - Wei-Jun Tian
- 2 Department of General Surgery, Tianjin Medical University General Hospital, Heping District, Tianjin, China
| | - Jie Zhang
- 2 Department of General Surgery, Tianjin Medical University General Hospital, Heping District, Tianjin, China
| | - Chang-Xin Jiang
- 3 Department of Pathology, Tianjin Medical University General Hospital, Heping District, Tianjin, China
| | - Hui-Qi Qu
- 4 Department of Paediatrics, Division of Endocrinology, 54473 McGill University Health Centre Research Institute, Montréal, Québec, Canada
| | - Mei Zhu
- 1 Department of Endocrinology, Tianjin Medical University General Hospital, Heping District, Tianjin, China
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17
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Zandee WT, Kamp K, van Adrichem RC, Feelders RA, de Herder WW. Effect of hormone secretory syndromes on neuroendocrine tumor prognosis. Endocr Relat Cancer 2017; 24:R261-R274. [PMID: 28483790 DOI: 10.1530/erc-16-0538] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2017] [Accepted: 05/08/2017] [Indexed: 12/12/2022]
Abstract
The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete a wider variety of hormones, like insulin, glucagon and gastrin leading to distinct clinical syndromes. Historically mortality in patients with functioning NETs was high due to the complications caused by the hypersecretion of hormones. This has been reduced with several drugs: proton-pump inhibitors decrease acid secretion caused by gastrinomas. Somatostatin analogs can inhibit the secretion of multiple hormones and these are now the cornerstone for treating patients with a gastroenteropancreatic NET. However, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs and everolimus can also decrease symptoms of hypersecretion and increase progression-free survival. Several factors affect the survival in patients with a functioning NET. Complications of hypersecretion negatively impact survival; however, secretion of hormones is also often a sign of a well-differentiated NET and due to the symptoms, functioning NETs can be detected in an earlier stage suggesting a positive effect on prognosis. The effect on survival is also dependent on the type of hormone being secreted. This review aims to study the effect of hormone secretion on the prognosis of NETs with the contemporary treatments options available today.
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Affiliation(s)
- Wouter T Zandee
- Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC, Rotterdam, the Netherlands
| | - Kimberly Kamp
- Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC, Rotterdam, the Netherlands
| | - Roxanne C van Adrichem
- Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC, Rotterdam, the Netherlands
| | - Richard A Feelders
- Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC, Rotterdam, the Netherlands
| | - Wouter W de Herder
- Department of Internal MedicineSector Endocrinology, ENETS Centre of Excellence, Erasmus MC, Rotterdam, the Netherlands
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Zhou B, Duan J, Yan S, Zhou J, Zheng S. Prognostic factors of long-term outcome in surgically resectable pancreatic neuroendocrine tumors: A 12-year experience from a single center. Oncol Lett 2017; 13:1157-1164. [PMID: 28454228 PMCID: PMC5403230 DOI: 10.3892/ol.2017.5561] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2015] [Accepted: 11/21/2016] [Indexed: 01/28/2023] Open
Abstract
The present study was performed to assess the prognostic factors with respect to patient survival and clinicopathological characteristics for patients who underwent surgery for pancreatic neuroendocrine tumors (PNETs). A retrospective review of patients pathologically diagnosed with PNETs at the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, Zhejiang, China) between September 2002 and September 2013 was conducted. The clinicopathological findings, overall survival (OS) rate and disease-free survival (DFS) rate of the patients with PNETs were analyzed. Prognostic factors were determined by univariate and multivariate analyses. A total of 104 patients were selected. The median age at presentation was 52 years (range, 19–76 years). The most common surgical procedure was distal pancreatectomy (51.0%), followed by pancreaticoduodenectomy (27.9%) and local resection of the pancreas (16.3%). The majority of the tumors were of low or moderate grade (93.3%, grade 1 or 2) and were local or regional stage (92.3%). The 1-, 3- and 5-year OS rates were 95, 85 and 73%, respectively. Meanwhile, the 1-, 3- and 5-year DFS rates were 86, 72 and 68%, respectively. The OS and DFS rates were significantly different with regard to the grade (grades 1, 2 and 3; P<0.001) and stage (local, regional and distant disease; P<0.001). Furthermore, patients with a low Ki-67 index experienced superior OS and DFS rates compared with patients with a high Ki-67 index (P<0.001). The presence of lymph node metastasis was predictive of inferior OS and DFS rates compared with the absence of lymph node metastasis (P<0.001). OS rate for PNETs was significantly affected by resection margin status (P<0.001). In multivariable analysis, the significant factors associated with OS rate were stage (P=0.02), grade (P<0.001), lymph node status (P=0.025), Ki-67 index (P=0.031) and resection margin status (P<0.001). Meanwhile, stage (P=0.001), grade (P=0.017), lymph node status (P=0.02) and Ki-67 index (P=0.016) were prognostic factors for DFS rate. In conclusion, grade, stage, Ki-67 index and lymph node involvement are significant prognostic factors for OS and DFS rates in surgically resectable PNETs. Furthermore, surgical margin status may also be an independent predictor for the prognosis of PNETs. It is anticipated that these findings may provide useful predictors of clinical survival, particularly in the setting of resected disease.
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Affiliation(s)
- Bo Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Jixuan Duan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Sheng Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Jie Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
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19
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Chan DL, Segelov E, Singh S. Everolimus in the management of metastatic neuroendocrine tumours. Therap Adv Gastroenterol 2017; 10:132-141. [PMID: 28286565 PMCID: PMC5330615 DOI: 10.1177/1756283x16674660] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Neuroendocrine tumours are increasing in incidence and cause a variety of symptoms. The mammalian target of rapamycin (mTOR) pathway plays a key role in neuroendocrine tumour (NET) pathogenesis, leading to increased lipid synthesis, protein synthesis and cellular growth. Upregulation of this pathway is noted in both hereditary and sporadic NETs. This understanding has led to investigations of mTOR inhibitors as therapy for metastatic NETs. After promising preclinical findings, everolimus, an mTOR inhibitor, was trialled in the RADIANT-1-4 studies on patients with advanced, well differentiated NETs. RADIANT-3 and RADIANT-4 established the efficacy of everolimus in improving progression-free survival (PFS) for metastatic NET of pancreatic, lung and gastrointestinal origin, leading to the US Food and Drug Administration (FDA) approval for its use in tumour control in those settings. Everolimus treatment is generally well tolerated; common adverse events include stomatitis, diarrhoea, rash and hyperglycaemia. Although discontinuation rates are low, many patients may require dose modification to successfully continue therapy. The combination of everolimus with somatostatin analogues (SSAs) (such as octreotide or pasireotide) or other targeted agents such as bevacizumab has not produced additional incremental benefit, and dual biologic therapy is not used widely. Ongoing trials are investigating everolimus compared with chemotherapy, optimal sequencing of therapy and combination of everolimus with radiotherapy. Future research should concentrate on identification of predictive biomarkers for benefit from mTOR therapy and include quality of life as a measure.
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Affiliation(s)
| | - Eva Segelov
- St Vincent’s Hospital, New South Wales, Australia
| | - Simron Singh
- Odette Cancer Centre, 2075 Bayview Avenue, Room T2 047, Toronto, ON, Canada M4N 3M5
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20
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Jilesen APJ, van Eijck CHJ, in't Hof KH, van Dieren S, Gouma DJ, van Dijkum EJMN. Postoperative Complications, In-Hospital Mortality and 5-Year Survival After Surgical Resection for Patients with a Pancreatic Neuroendocrine Tumor: A Systematic Review. World J Surg 2016; 40:729-48. [PMID: 26661846 PMCID: PMC4746219 DOI: 10.1007/s00268-015-3328-6] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Studies on postoperative complications and survival in patients with pancreatic neuroendocrine tumors (pNET) are sparse and randomized controlled trials are not available. We reviewed all studies on postoperative complications and survival after resection of pNET. A systematic search was performed in the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE from 2000-2013. Inclusion criteria were studies of resected pNET, which described postoperative complications separately for each surgical procedure and/or 5-year survival after resection. Prospective and retrospective studies were pooled separately and overall pooled if heterogeneity was below 75%. The random-effect model was used. Overall, 2643 studies were identified and after full-text analysis 62 studies were included. Pancreatic fistula (PF) rate of the prospective studies after tumor enucleation was 45%; PF-rates after distal pancreatectomy, pancreatoduodenectomy, or central pancreatectomy were, respectively, 14-14-58%. Delayed gastric emptying rates were, respectively, 5-5-18-16%. Postoperative hemorrhage rates were, respectively, 6-1-7-4%. In-hospital mortality rates were, respectively, 3-4-6-4%. The 5-year overall survival (OS) and disease-specific survival (DSS) of resected pNET without synchronous resected liver metastases were, respectively, 85-93%. Heterogeneity between included studies on 5-year OS in patients with synchronous resected liver metastases was too high to pool all studies. The 5-year DSS in patients with liver metastases was 80%. Morbidity after pancreatic resection for pNET was mainly caused by PF. Liver resection in patients with liver metastases seems to have a positive effect on DSS. To reduce heterogeneity, ISGPS criteria and uniform patient groups should be used in the analysis of postoperative outcome and survival.
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Affiliation(s)
- Anneke P J Jilesen
- Department of Surgery, Academic Medical Center, Meibergdreef 9, P. O. Box 22660, 1105 AZ, Amsterdam, The Netherlands.
| | | | - K H in't Hof
- Department of Surgery, Academic Medical Center, Meibergdreef 9, P. O. Box 22660, 1105 AZ, Amsterdam, The Netherlands
| | - S van Dieren
- Department of Methodology and Statistics Clinical Research Unit, Academic Medical Center, Amsterdam, The Netherlands
| | - Dirk J Gouma
- Department of Surgery, Academic Medical Center, Meibergdreef 9, P. O. Box 22660, 1105 AZ, Amsterdam, The Netherlands
| | - Els J M Nieveen van Dijkum
- Department of Surgery, Academic Medical Center, Meibergdreef 9, P. O. Box 22660, 1105 AZ, Amsterdam, The Netherlands
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Qi XY, Ma L, Lu Q, Yang LL, Li JW, Ling WW, Luo Y. Ultrasonographic features and differential diagnosis of solid pseudopapillary tumors of the pancreas. Shijie Huaren Xiaohua Zazhi 2016; 24:1269. [DOI: 10.11569/wcjd.v24.i8.1269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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22
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Wang G, Ma Y, Qu FZ, Sun B. Status quo of diagnosis and treatment of pancreatic neuroendocrine tumors. Shijie Huaren Xiaohua Zazhi 2015; 23:3817-3823. [DOI: 10.11569/wcjd.v23.i24.3817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are clinically rare digestive system tumors, which are characterized by insidious onset, a high potential of malignant tendency and a high misdiagnosis rate. In recent years, with the gradual increase of incidence and the continuous improvement of clinical diagnosis level, the detection and diagnosis rates of PNETs have been constantly increasing. In view of their malignant potential, early diagnosis and surgical intervention are essential. Therefore, clinicians should raise their awareness of this disease so as to effectively improve the diagnosis and treatment.
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23
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The efficacy of 177Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis. Eur J Nucl Med Mol Imaging 2015; 42:1964-70. [DOI: 10.1007/s00259-015-3155-x] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 07/24/2015] [Indexed: 12/16/2022]
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24
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Gebauer N, Schmidt-Werthern C, Bernard V, Feller AC, Keck T, Begum N, Rades D, Lehnert H, Brabant G, Thorns C. Genomic landscape of pancreatic neuroendocrine tumors. World J Gastroenterol 2014; 20:17498-17506. [PMID: 25516664 PMCID: PMC4265611 DOI: 10.3748/wjg.v20.i46.17498] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2014] [Revised: 05/03/2014] [Accepted: 07/25/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the prognostic role of genomic stability and copy number alterations (CNAs) pancreatic neuroendocrine tumors (PanNETs).
METHODS: A high-resolution array-based comparative genomic hybridization approach was utilized in order to investigate and quantify chromosomal aberrations in a panel of 37 primary PanNET and 11 metastatic samples. DNA samples were extracted from formalin-fixed and paraffin-embedded tumor specimen. Genomic findings were correlated with histopathological and immunohistochemical data. Moreover, the dataset was subjected to employing an unsupervised hierarchical clustering analysis approach utilizing Euclidean distance and average linkage and associations between genomically defined tumor groups and recurrent CNAs or clinicopathological features of the study group were assessed.
RESULTS: Numerous chromosomal aberrations were recurrently detected in both, primary tumor samples and metastases. Copy number gains were most frequently observed at 06p22.2-p22.1 (27.1%), 17p13.1 (20.8%), 07p21.3-p21.2 (18.8%), 09q34.11 (18.8%). Genomic losses were significantly less frequent and the only recurrent aberration affected 08q24.3 (6.3%). Moreover, we detected a high degree of genomic heterogeneity between primary tumors and metastatic lesions. Unsupervised hierarchical clustering of loci affected by CNAs in more than 3 primary tumor samples revealed two genetically distinct tumor groups as well as two chromosomal clusters of genomic imbalances indicating a small subset of tumors with common molecular features (13.5%). Aberrations affecting 6p22.2-22.1, 8q24.3, 9q34.11 and 17p13.1 (P = 0.011; 0.003; 0.003; 0.001), were significantly associated with a poorer survival prognosis.
CONCLUSION: This study suggests that several frequent CNAs in numerous candidate regions are involved in the pathogenesis and metastatic progression of PanNET.
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Pancreatic neuroendocrine tumor: A multivariate analysis of factors influencing survival. Eur J Surg Oncol 2014; 40:1564-71. [PMID: 25086992 DOI: 10.1016/j.ejso.2014.06.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Revised: 05/29/2014] [Accepted: 06/17/2014] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The outcomes of pancreatic neuroendocrine tumors are extremely diverse, and determining the best strategy, optimal timing of therapy and the therapeutic results depend on understanding prognostic factors. We determined the clinical, radiological and histological factors associated with survival and tumor recurrence for patients with pancreatic neuroendocrine tumor. METHODS From January 1, 1991 to December 31, 2011, 127 patients with pancreatic neuroendocrine tumor underwent pancreatectomy. The variables including clinical characteristics, surgical data and pathological findings were examined by univariate and multivariate analyses. RESULTS There were 103 patients with non-functional tumors (81%). Sixty-four patients (50%) underwent left pancreatectomy, 51 (42%) patients underwent pancreatico-duodenectomy, 12 (9%) patients underwent enucleation and 2 patients (1%) underwent central pancreatectomy. Forty-eight patients (38%) had synchronous liver metastases. Six patients (5%) required portal vein resection, and 19 (15%) patients required enlarged "en-bloc" resection of adjacent organs. The overall morbidity and mortality rates were 48% and 2.3%, respectively. The 1-, 3- and 5-year overall survival rates were 94%, 84%, and 74%, respectively. In multivariate analyses, synchronous liver metastases (p = 0.02) and portal vein resection (p < 0.01) were independent prognostic factors of survival. CONCLUSIONS Synchronous liver metastases and portal vein resection were found to be independent factors influencing survival.
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Boyar Cetinkaya R, Vatn M, Aabakken L, Bergestuen DS, Thiis-Evensen E. Survival and prognostic factors in well-differentiated pancreatic neuroendocrine tumors. Scand J Gastroenterol 2014; 49:734-41. [PMID: 24679166 DOI: 10.3109/00365521.2014.903432] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Pancreatic neuroendocrine tumors (P-NETs) account for 2-3% of all pancreatic neoplasms. The aim of our study was to investigate survival and prognostic factors in patients with P-NETs. MATERIAL AND METHODS We retrospectively reviewed the medical records of 114 patients diagnosed with well-differentiated P-NETs from 1982 through 2010. We studied demographical, clinical, radiological, and histopathological characteristics. RESULTS Median age at diagnosis was 57 years (range 32-83); 53% were men and 78% had nonfunctional tumors. The most common presenting symptoms were abdominal pain (41%), weight loss (36%), and diarrhea (25%); 19% of the tumors were incidental findings. Median duration of symptoms before diagnosis was 4 months, 3 months for nonfunctional, and 12 months for functional tumors (p < 0.001). At diagnosis, 32.5% patients had local, 22.8% had regional, and 44.7% had distant disease. Men had more often distant disease at diagnosis (p = 0.02). Median survival was 6.6 years (95% confidence interval [CI]: 4.0-9.2). Overall 5-year survival was 53.9% (95% CI: 43.4-63.3). For those with local disease and those with distant disease at diagnosis, the 5-year survivals were 70.2% (95% CI: 49.9-83.6) and 33.0% (95% CI: 19.7-46.7), respectively. Surgery with curative intent was performed on 46 patients. Newly detected liver metastases were diagnosed up to 10 years after surgery in this group. In patients with metastases, palliative surgery (debulking) did not have a significant effect on survival compared to those who had no surgery. CONCLUSION Distant metastases, Ki-67 > 2%, nonfunctional tumors, elevated level of chromogranin A, and palliative treatment were associated with poor survival.
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Affiliation(s)
- Raziye Boyar Cetinkaya
- Department of Gastroenterology, Rikshospitalet, Oslo University Hospital , Oslo , Norway
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Chen MH, Yeh YC, Shyr YM, Jan YH, Chao Y, Li CP, Wang SE, Tzeng CH, Chang PMH, Liu CY, Chen MH, Hsiao M, Huang CYF. Expression of gremlin 1 correlates with increased angiogenesis and progression-free survival in patients with pancreatic neuroendocrine tumors. J Gastroenterol 2013; 48:101-8. [PMID: 22706573 DOI: 10.1007/s00535-012-0614-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2011] [Accepted: 05/09/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs). METHODS The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification. RESULTS The presence of expression of GREM1 (p = 0.016) and high MVD (p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD (p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas (p < 0.001). CONCLUSIONS GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs.
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Affiliation(s)
- Ming-Huang Chen
- Institute of Clinical Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong St., Taipei, 112, Taiwan
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Martin-Perez E, Capdevila J, Castellano D, Jimenez-Fonseca P, Salazar R, Beguiristain-Gomez A, Alonso-Orduña V, Martinez Del Prado P, Villabona-Artero C, Diaz-Perez JA, Monleon A, Marazuela M, Pachon V, Sastre-Valera J, Sevilla I, Castaño A, Garcia-Carbonero R. Prognostic factors and long-term outcome of pancreatic neuroendocrine neoplasms: Ki-67 index shows a greater impact on survival than disease stage. The large experience of the Spanish National Tumor Registry (RGETNE). Neuroendocrinology 2013; 98:156-68. [PMID: 23988576 DOI: 10.1159/000355152] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Accepted: 08/21/2013] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Pancreatic neuroendocrine neoplasms (PNENs) are uncommon neoplasms with a wide spectrum of clinical behavior. The objective of this study was to assess in a large cohort of patients the relative impact of prognostic factors on survival. METHODS From June 2001 through October 2010, 1,271 patients were prospectively registered online (www.getne.org) at the Spanish National Cancer Registry for Gastroenteropancreatic Neuroendocrine Tumors (RGETNE) by participating centers. Clinical and histopathological features were assessed as potential prognostic factors by uni- and multivariate analyses. RESULTS Of 483 PNENs, 171 (35%) were functional (F) and 312 (65%) non-functional (NF). NF-PNENs were associated with a higher incidence of histological features denoting more aggressive disease, such as poor tumor differentiation, Ki-67 >20%, or vascular invasion (NF- vs. F-PNENs, respectively, p < 0.05). Nevertheless, functionality was not a significant predictor of survival (p = 0.19). Stage at diagnosis, Ki-67 index, tumor differentiation and surgical resection of the primary tumor were all significant prognostic factors in univariate analysis. However, Ki-67 (>20 vs. ≤2%) (hazard ratio (HR) 2.21, p = 0.01) and surgical resection (yes vs. no) (HR 0.92, p = 0.001) were the only independent predictors of survival in multivariate analysis. Among patients who underwent surgery, high Ki-67 index (HR 10.37, p = 0.02) and poor differentiation (HR 8.16, p = 0.03) were the only independent predictors of clinical outcome. CONCLUSION Ki-67 index and tumor differentiation are key prognostic factors influencing survival of patients with PNENs and, in contrast to what it is observed for other solid malignancies, they seem to have a greater impact on survival than the extent of disease. This should be borne in mind by physicians in order to appropriately tailor therapeutic strategies and surveillance of these patients.
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Watzka FM, Laumen C, Fottner C, Weber MM, Schad A, Lang H, Musholt TJ. Resection strategies for neuroendocrine pancreatic neoplasms. Langenbecks Arch Surg 2012; 398:431-40. [DOI: 10.1007/s00423-012-1024-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2012] [Accepted: 10/23/2012] [Indexed: 02/07/2023]
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Specificity and sensitivity of ⁹⁹mTc-EDDA/HYNIC-Tyr³-octreotide (⁹⁹mTc-TOC) for imaging neuroendocrine tumors. Nucl Med Commun 2012; 33:69-79. [PMID: 21970835 DOI: 10.1097/mnm.0b013e32834cecfe] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVES Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the ⁹⁹mTc-EDDA-HYNIC-Tyr³octreotide (⁹⁹mTc-TOC) to image and localize NETs and their metastases. MATERIALS AND METHODS Freeze-dried kits containing 0.0125 mg HYNIC-octreotide and co-ligands were easily labeled and quality controlled within the hospital radiopharmacy. Fifty-six consecutive Mexican patients with a previous presumptive diagnosis of NETs underwent several clinical and laboratory studies and were referred to the Nuclear Medicine Department for a routine scan with ⁹⁹mTc-TOC. The patients were injected with 500-600 MBq ⁹⁹mTc-TOC, and whole-body images were obtained 2 h later with a SPECT or a SPECT/CT camera. Two nuclear medicine physicians observed the images and classified them as 17 negative and 39 positive. After correlating the image of each patient with our 'gold standard' (biopsy, clinical history, morphological images, and tumor marker assays), the ⁹⁹mTc-TOC images were classified by the same two physicians as 12 true negatives, five false negatives, 38 true positives and one false positive. RESULTS The validity of ⁹⁹mTc-TOC in terms of relative frequencies with corresponding 95% confidence intervals were as follows: 92.3% (64-100%) specificity; 88.4% (78-97%) sensitivity; and the agreement beyond chance was 73% (60-84%). The positive predictive value was 97.4% (87-100%); the negative predicted value was 70.6% (48-93%); the accuracy was 89.3% (89-97%); and the prevalence was 76.8% (64-87%). CONCLUSION Because of these high values, we strongly recommend scintigraphy with the Mexican-produced ⁹⁹mTc-TOC for the localization of NETs and their metastases, and we conclude that it is a good tool for detecting neuroendocrine disease in a Mexican population.
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Prognostic factors and survival in patients with neuroendocrine tumors of the pancreas. Tumour Biol 2011; 32:697-705. [PMID: 21479734 DOI: 10.1007/s13277-011-0170-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2011] [Accepted: 03/07/2011] [Indexed: 12/13/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are uncommon malignancies. The purpose of this study was to identify the prognostic factors of pancreatic neuroendocrine tumors at a single center in China. Clinical data of 27 patients with PNETs treated at the Sun Yat-sen University Cancer Center between January 1995 and December 2010 were retrospectively reviewed. Survival was estimated with the Kaplan-Meier methodology. Twenty-three patients (85.2%) had nonfunctional tumors and four patients (14.8%) had functional tumors. The majority of PNETs located in the body and/or tail of the pancreas in 20 patients (74.1%). All Patients with functional tumors cause syndromes related to hormone overproduction. Anorexia, nausea, vomiting, obstructive jaundice, weight loss, and incidental mass were more common in patients with nonfunctional tumors. The median follow-up time was 40 months. The overall 1-, 2-, and 5-year accumulative survival rates were 91%, 81%, and 81%, respectively. In univariate analysis, factors associating with significantly better survival included macroscopically radical resection of the primary tumor, tumor-node-metastasis (TNM) staging, World Health Organization (WHO) classification, and palliative chemotherapy. Macroscopically radical resection of the primary tumor, TNM staging, WHO classification, and palliative chemotherapy were prognostic variables which may emerge as a practical clinical tool to predict survival.
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