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Sharma A, Muralitharan M, Ramage J, Clement D, Menon K, Srinivasan P, Elmasry M, Reed N, Seager M, Srirajaskanthan R. Current Management of Neuroendocrine Tumour Liver Metastases. Curr Oncol Rep 2024; 26:1070-1084. [PMID: 38869667 PMCID: PMC11416395 DOI: 10.1007/s11912-024-01559-w] [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] [Accepted: 05/22/2024] [Indexed: 06/14/2024]
Abstract
PURPOSE OF REVIEW This article aims to illustrate the current state of investigations and management of liver metastases in patients with Neuroendocrine Neoplasms. Neuroendocrine tumours (NETs) are rising in incidence globally and have become the second most prevalent gastrointestinal malignancy in UK and USA. Frequently, patients have metastatic disease at time of presentation. The liver is the most common site of metastases for gastro-enteropancreatic NETs. Characterisation of liver metastases with imaging is important to ensure disease is not under-staged. RECENT FINDINGS Magnetic resonance imaging and positron emission tomography are now becoming standard of care for imaging liver metastases. There is an increasing armamentarium of therapies available for management of NETs and loco-regional therapy for liver metastases. The data supporting surgical and loco-regional therapy is reviewed with focus on role of liver transplantation. It is important to use appropriate imaging and classification of NET liver metastases. It is key that decisions regarding approach to treatment is undertaken in a multidisciplinary team and that individualised approaches are considered for management of patients with metastatic NETs.
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Affiliation(s)
- Aditya Sharma
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K
| | | | - John Ramage
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Dominique Clement
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Krishna Menon
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Parthi Srinivasan
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Mohamed Elmasry
- Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K
| | - Nick Reed
- Department of Oncology, Beatson Centre, G12 0YN, Glasgow, U.K
| | - Matthew Seager
- Department of Radiology, King's College Hospital, SE5 9RS, London, U.K
| | - Rajaventhan Srirajaskanthan
- Department of Gastroenterology, King's College Hospital, SE5 9RS, London, U.K..
- Neuroendocrine Tumour Unit, Institute of Liver Studies, King's College Hospital, SE5 9RS, London, U.K..
- Neuroendocrine Tumour Unit Institute of liver studies, King's College Hospital, SE5 9RS, London, U.K..
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2
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He B, Sun H, Bao M, Li H, He J, Tian G, Wang B. A cross-cohort computational framework to trace tumor tissue-of-origin based on RNA sequencing. Sci Rep 2023; 13:15356. [PMID: 37717102 PMCID: PMC10505149 DOI: 10.1038/s41598-023-42465-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 09/11/2023] [Indexed: 09/18/2023] Open
Abstract
Carcinoma of unknown primary (CUP) is a type of metastatic cancer with tissue-of-origin (TOO) unidentifiable by traditional methods. CUP patients typically have poor prognosis but therapy targeting the original cancer tissue can significantly improve patients' prognosis. Thus, it's critical to develop accurate computational methods to infer cancer TOO. While qPCR or microarray-based methods are effective in inferring TOO for most cancer types, the overall prediction accuracy is yet to be improved. In this study, we propose a cross-cohort computational framework to trace TOO of 32 cancer types based on RNA sequencing (RNA-seq). Specifically, we employed logistic regression models to select 80 genes for each cancer type to create a combined 1356-gene set, based on transcriptomic data from 9911 tissue samples covering the 32 cancer types with known TOO from the Cancer Genome Atlas (TCGA). The selected genes are enriched in both tissue-specific and tissue-general functions. The cross-validation accuracy of our framework reaches 97.50% across all cancer types. Furthermore, we tested the performance of our model on the TCGA metastatic dataset and International Cancer Genome Consortium (ICGC) dataset, achieving an accuracy of 91.09% and 82.67%, respectively, despite the differences in experiment procedures and pipelines. In conclusion, we developed an accurate yet robust computational framework for identifying TOO, which holds promise for clinical applications. Our code is available at http://github.com/wangbo00129/classifybysklearn .
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Affiliation(s)
- Binsheng He
- School of Pharmacy, Changsha Medical University, Changsha, 410219, People's Republic of China
- Academician Workstation, Changsha Medical University, Changsha, 410219, People's Republic of China
| | - Hongmei Sun
- Department of Medical Oncology, The Cancer Hospital of Jia Mu Si, Jiamusi, People's Republic of China
| | - Meihua Bao
- Academician Workstation, Changsha Medical University, Changsha, 410219, People's Republic of China
| | - Haigang Li
- Academician Workstation, Changsha Medical University, Changsha, 410219, People's Republic of China
| | - Jianjun He
- School of Pharmacy, Changsha Medical University, Changsha, 410219, People's Republic of China
- Academician Workstation, Changsha Medical University, Changsha, 410219, People's Republic of China
| | - Geng Tian
- Geneis Beijing Co., Ltd., Beijing, 100102, People's Republic of China
- Qingdao Genesis Institute of Big Data Mining and Precision Medicine, Qingdao, 266000, Shandong, People's Republic of China
| | - Bo Wang
- Geneis Beijing Co., Ltd., Beijing, 100102, People's Republic of China.
- Qingdao Genesis Institute of Big Data Mining and Precision Medicine, Qingdao, 266000, Shandong, People's Republic of China.
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Xue J, Li X, Qu N, Wu Z, Wang G, Chenhuang Z, Cao X. A case report of diagnosis of liver metastasis of medullary thyroid carcinoma by multimodal ultrasound. Radiol Case Rep 2023; 18:2279-2281. [PMID: 37128255 PMCID: PMC10147952 DOI: 10.1016/j.radcr.2023.03.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 03/12/2023] [Accepted: 03/17/2023] [Indexed: 05/03/2023] Open
Abstract
Medullary thyroid carcinoma is a rare malignant neuroendocrine tumor. Distant metastasis is difficult to detect early. It is most common in lung, liver, bone and brain. This case was reported as liver metastasis of medullary thyroid carcinoma in an elderly woman, but routine ultrasound findings were atypical. After a series of relevant imaging examinations, contrast-enhanced ultrasound and ultrasound-guided puncture biopsy were used to confirm the nature of the intrahepatic lesions. Therefore, we believe that multimodal ultrasound is of great value in the diagnosis of liver metastasis of medullary thyroid carcinoma.
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Affiliation(s)
- Jie Xue
- Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Department of Ultrasound, 20 Yuhuangding East Road, Zhifu District, Yantai City, Shandong Province China, 264000
| | - Xinying Li
- School of Medical Imaging, Binzhou Medical University, Shandong, Yantai, 264003, China
| | - Nina Qu
- Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Department of Ultrasound, 20 Yuhuangding East Road, Zhifu District, Yantai City, Shandong Province China, 264000
| | - Zhihui Wu
- School of Medical Imaging, Binzhou Medical University, Shandong, Yantai, 264003, China
| | - Guoyun Wang
- School of medicine, Qingdao University, Shandong, Qingdao, 266005, China
| | - Zhuonan Chenhuang
- School of Medical Imaging, Weifang Medical University, Shandong, Weifang, 261021, China
| | - Xiaoli Cao
- Qingdao University Medical College Affiliated Yantai Yuhuangding Hospital, Department of Ultrasound, 20 Yuhuangding East Road, Zhifu District, Yantai City, Shandong Province China, 264000
- Corresponding author.
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4
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Prospective Multicentric Assessment of 68Ga-DOTANOC PET/CT in Grade 1-2 GEP-NET. Cancers (Basel) 2023; 15:cancers15020513. [PMID: 36672462 PMCID: PMC9856693 DOI: 10.3390/cancers15020513] [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: 12/04/2022] [Revised: 01/11/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs.
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Koffas A, Giakoustidis A, Papaefthymiou A, Bangeas P, Giakoustidis D, Papadopoulos VN, Toumpanakis C. Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. Front Surg 2023; 10:1064145. [PMID: 36950054 PMCID: PMC10025557 DOI: 10.3389/fsurg.2023.1064145] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 02/07/2023] [Indexed: 03/08/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.
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Affiliation(s)
- Apostolos Koffas
- Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Correspondence: Apostolos Koffas
| | - Alexandros Giakoustidis
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Apostolis Papaefthymiou
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London, United Kingdom
| | - Petros Bangeas
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Giakoustidis
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Vasileios N Papadopoulos
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Christos Toumpanakis
- Centre for Gastroenterology, Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, United Kingdom
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Passand GT, Marichez A, Debordeaux F, Pinaquy JB, Chiche L. Serous cystadenoma mimicking cystic pancreatic neuroendocrine tumor on 68Ga-DOTATOC PET/CT. Diagn Interv Imaging 2022; 103:563-565. [PMID: 36280584 DOI: 10.1016/j.diii.2022.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/05/2022] [Accepted: 10/06/2022] [Indexed: 12/13/2022]
Affiliation(s)
- Goudarz T Passand
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Haut Lévêque Hospital, Bordeaux University Hospital, Pessac, 33600, France
| | - Arthur Marichez
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Haut Lévêque Hospital, Bordeaux University Hospital, Pessac, 33600, France; INSERM U1312 - Team 3 "Liver Cancers and Tumoral Invasion" - Bordeaux Institute of Oncology, University of Bordeaux, 33076, France.
| | - Frédéric Debordeaux
- Department of Nuclear Imaging, Haut Lévêque Hospital, Bordeaux University Hospital, Pessac, 33600, France
| | - Jean-Baptiste Pinaquy
- Department of Nuclear Imaging, Haut Lévêque Hospital, Bordeaux University Hospital, Pessac, 33600, France
| | - Laurence Chiche
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Haut Lévêque Hospital, Bordeaux University Hospital, Pessac, 33600, France; INSERM U1312 - Team 3 "Liver Cancers and Tumoral Invasion" - Bordeaux Institute of Oncology, University of Bordeaux, 33076, France
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7
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Hartrampf P, Werner R, Buck A. Theranostics bei gut bis mäßig differenzierten GEP-NEN. Zentralbl Chir 2022; 147:249-255. [DOI: 10.1055/a-1826-3423] [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 (NEN) sind seltene, heterogene und typischerweise langsam wachsende Tumoren. Die häufigsten Lokalisationen finden sich im gastro-entero-pankreatischen System
(GEP-NEN). NENs werden nach proliferativer Aktivität (Ki-67-Index) eingeteilt (G1–3). Gut differenzierte Tumoren exprimieren dabei typischerweise Somatostatinrezeptoren (SSTR), die als
Zielstruktur in der nuklearmedizinischen Theranostik dienen. Bei diesem Prinzip kann nach einer diagnostischen molekularen Bildgebung, meist mittels
Positronenemissionstomografie/Computertomografie (PET/CT), eine individuell zugeschnittene Peptidradiorezeptortherapie (PRRT) mit einem β-Strahler-markierten Radiopharmakon erfolgen. In
Metaanalysen zeigte die Diagnostik mittels SSTR-gerichteter PET/CT eine Sensitivität von 93% und eine Spezifität von 96%. Die SSTR-gerichtete Diagnostik kann auch zur radioaktiven Markierung
von Tumoren verwendet werden, um eine zielgerichtete Chirurgie zu ermöglichen. Die Indikation zur Einleitung einer PRRT soll stets in einer interdisziplinären Tumorkonferenz getroffen
werden. Ein Tumorprogress unter der vorangegangenen Therapie sollte dokumentiert sein. Die Therapie wird intravenös und insgesamt 4-mal in 8-wöchigem Abstand in spezialisierten
nuklearmedizinischen Zentren verabreicht. Die Wirksamkeit der PRRT wurde in der NETTER-1-Studie prospektiv untersucht und konnte eine signifikante Verbesserung des progressionsfreien
Überlebens (primärer Endpunkt) zeigen. Ausgehend von diesen Studienergebnissen steht mit Lutathera (177Lu-DOTATATE) inzwischen ein in Deutschland zugelassenes Radiopharmazeutikum zu
Behandlung von nicht resektablen oder metastasierten bzw. progredienten, gut differenzierten (G1 und G2), SSTR-positiven GEP-NEN zur Verfügung.
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Affiliation(s)
- Philipp Hartrampf
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Rudolf Werner
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Andreas Buck
- Klinik und Poliklinik für Nuklearmedizin, Universitätsklinikum Würzburg, Würzburg, Deutschland
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Yin B, Gao R, Xu Q, Wang X, Wu W. Surgical management for pancreatic neuroendocrine neoplasms with synchronous hepatic metastases: A literature review. SURGERY IN PRACTICE AND SCIENCE 2022. [DOI: 10.1016/j.sipas.2021.100055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Bodei L, Jayaprakasam VS, Kidd M, Gilardi L, Volterrani D, Paganelli G, Grana CM, Modlin IM. Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors. NUCLEAR ONCOLOGY 2022:933-974. [DOI: 10.1007/978-3-031-05494-5_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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10
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Chang A, Sherman SK, Howe JR, Sahai V. Progress in the Management of Pancreatic Neuroendocrine Tumors. Annu Rev Med 2021; 73:213-229. [PMID: 34669433 DOI: 10.1146/annurev-med-042320-011248] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous and orphan group of neoplasms that vary in their histology, clinical features, prognosis, and management. The treatment of PNETs is highly dependent on the stage at presentation, tumor grade and differentiation, presence of symptoms from hormonal overproduction or from local growth, tumor burden, and rate of progression. The US Food and Drug Administration has recently approved many novel treatments, which have altered decision making and positively impacted the care and prognosis of these patients. In this review, we focus on the significant progress made in the management of PNETs over the past decade, as well as the active areas of research. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Amy Chang
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA; ,
| | - Scott K Sherman
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa, Iowa City, Iowa 52242, USA; ,
| | - James R Howe
- Division of Surgical Oncology and Endocrine Surgery, Department of Surgery, University of Iowa, Iowa City, Iowa 52242, USA; ,
| | - Vaibhav Sahai
- Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA; ,
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11
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Cracolici V, Wang EW, Gardner PA, Snyderman C, Gargano SM, Chiosea S, Singhi AD, Seethala RR. SSTR2 Expression in Olfactory Neuroblastoma: Clinical and Therapeutic Implications. Head Neck Pathol 2021; 15:1185-1191. [PMID: 33929681 PMCID: PMC8633213 DOI: 10.1007/s12105-021-01329-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 04/17/2021] [Indexed: 11/26/2022]
Abstract
Somatostatin receptor 2 (SSTR2) expression has previously been documented in olfactory neuroblastoma (ONB). Here, we fully characterize SSTR2 expression in ONB and correlate staining results with clinicopathologic parameters including Hyams grade. We also assess SSTR2 immunohistochemistry expression in various histologic mimics of ONB to assess its diagnostic functionality. 78 ONBs (51 primary biopsies/excisions and 27 recurrences/metastases) from 58 patients were stained for SSTR2. H-scores based on intensity (0-3 +) and percentage of tumor cells staining were assigned to all cases. 51 histologic mimics were stained and scored in an identical fashion. 77/78 (99%) ONB cases demonstrated SSTR2 staining (mean H-score: 189, range: 0-290). There were no significant differences in staining between primary tumors and recurrences/metastases (mean H-score: 185 vs 198). Primary low-grade ONB had somewhat stronger staining than high-grade tumors (mean H-score: 200 vs 174). SSTR2 expression had no prognostic value when considering disease-free or disease-specific survival. SSTR2 staining is significantly higher in ONB than its histologic mimics (mean H-score: 189 vs 12.9, p < 0.001) suggesting a potential use of the marker in diagnosis of ONB. In conclusion, SSTR2 is consistently expressed in ONB suggesting a role for somatostatin-analog based imaging and therapy in this disease. More generally, SSTR2 may be another marker of neuroendocrine differentiation in ONB.
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Affiliation(s)
- Vincent Cracolici
- Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
- , 9500 Euclid Avenue, L25, Cleveland, OH, USA.
| | - Eric W Wang
- Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Paul A Gardner
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Carl Snyderman
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Stacey M Gargano
- Department of Pathology and Laboratory Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Simion Chiosea
- Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Aatur D Singhi
- Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Raja R Seethala
- Department of Pathology and Laboratory Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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12
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Wu W, Chen J, Bai C, Chi Y, Du Y, Feng S, Huo L, Jiang Y, Li J, Lou W, Luo J, Shao C, Shen L, Wang F, Wang L, Wang O, Wang Y, Wu H, Xing X, Xu J, Xue H, Xue L, Yang Y, Yu X, Yuan C, Zhao H, Zhu X, Zhao Y. The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020). JOURNAL OF PANCREATOLOGY 2021; 4:1-17. [DOI: 10.1097/jp9.0000000000000064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Abstract
Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
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Affiliation(s)
- Wenming Wu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Yihebali Chi
- Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Yiqi Du
- Department of Gastroenterology, Changhai Hospital Affiliated to Navy Medical University, Shanghai
| | - Shiting Feng
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Li Huo
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Yuxin Jiang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital of Fudan University
| | - Jie Luo
- Department of Pathology, China-Japan Friendship Hospital, Beijing
| | - Chenghao Shao
- Department of Pancreatic-biliary Surgery, Changzheng Hospital, Navy Medical University, Shanghai
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing
| | - Feng Wang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province
| | - Liwei Wang
- Department of Oncology, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai
| | - Ou Wang
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Yu Wang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Huanwen Wu
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Xiaoping Xing
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Jianming Xu
- Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing
| | - Huadan Xue
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Ling Xue
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Beijing
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing
| | - Xiongzeng Zhu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yupei Zhao
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
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Essentials of Insulinoma Localization with Selective Arterial Calcium Stimulation and Hepatic Venous Sampling. J Clin Med 2020; 9:jcm9103091. [PMID: 32992761 PMCID: PMC7601191 DOI: 10.3390/jcm9103091] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 09/19/2020] [Accepted: 09/21/2020] [Indexed: 12/25/2022] Open
Abstract
Insulinomas are the most common functional pancreatic neuroendocrine tumor. Most insulinomas can be localized non-invasively with cross-sectional and nuclear imaging. Selective arterial calcium stimulation and hepatic venous sampling is an effective and safe minimally-invasive procedure for insulinoma localization that may be utilized when non-invasive techniques are inconclusive. The procedure’s technical success and proper interpretation of its results is dependent on the interventional radiologist’s knowledge of normal and variant pancreatic arterial perfusion. Accurate pre-operative localization aids in successful surgical resection. Technical and anatomic considerations of insulinoma localization with selective arterial calcium stimulation and hepatic venous sampling are reviewed.
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Abstract
CLINICAL/METHODICAL ISSUE Conventional imaging tests like computed tomography (CT) cannot visualize somatostatin receptor (SSTR) expression on the tumor cell surface. STANDARD RADIOLOGICAL METHODS For imaging of SSTR-expressing tumors conventional morphological imaging tests such as CT or magnetic resonance imaging (MRI) are employed. METHODICAL INNOVATIONS Molecular imaging of SSTR expression on the tumor cell surface, in particular by using (whole body) single photon emission computed tomography (SPECT) and positron emission tomography (PET), are considered the current standard of care. Only the use of CT enables for exact localization of putative sites of disease (hybrid imaging). PERFORMANCE Hybrid SPECT/CT and PET/CT are of utmost importance for staging and monitoring of treatment efficacy. SSTR-PET is superior to SPECT and the PET radiotracer 68Ga-DOTATATE has been approved in multiple countries. In addition, SSTR positivity revealed by SPECT or PET pave the way for a peptide receptor radionuclide therapy (PRRT). Such a theranostic approach enables for systemic or locoregional radiation with β‑emitting radionuclides, which are linked to the identical amino acid peptide used for PET or SPECT imaging. The prospective, randomized Netter‑1 trial has shown significant benefit for patients receiving PRRT. ACHIEVEMENTS A combined use of conventional and functional imaging tests is superior to conventional imaging alone and allows for identification of suitable candidates for a theranostic approach. PRACTICAL RECOMMENDATIONS In case of clinical suspicion or after having obtained histological evidence, hybrid SSTR-SPECT/CT or -PET/CT should be performed, preferably in a dedicated molecular imaging center.
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15
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Basu S, Parghane RV, Naik C. Clinical efficacy of 177Lu-DOTATATE peptide receptor radionuclide therapy in thyroglobulin-elevated negative iodine scintigraphy: A "not-so-promising" result compared to GEP-NETs. World J Nucl Med 2020; 19:205-210. [PMID: 33354174 PMCID: PMC7745860 DOI: 10.4103/wjnm.wjnm_21_19] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Accepted: 05/26/2019] [Indexed: 01/09/2023] Open
Abstract
This study aimed at assessing the performance of 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) in de-differentiated thyroid carcinoma thyroglobulin-elevated negative iodine scintigraphy (TENIS) in terms of clinical efficacy and outcome. This is a retrospective analysis of patients of TENIS who had undergone PRRT in a tertiary care setting. The selected patients were analyzed for the following parameters: (i) the patient characteristics, (ii) the metastatic burden, (iii) study of PRRT cycles and activity, (iv) response assessment (undertaken by three-parameter scale: symptomatic including Karnofsky/Lansky Performance scoring, biochemical and scan features) employing predefined criteria (detailed in methods), and (v) Grade III/IV hematological or renal toxicity. According to the qualitative uptake of the tracer in somatostatin receptor (SSTR)-based imaging (with either 99mTc-HYNIC-TOC/68Ga-DOTATATE), the lesions were divided into the following four categories: Grade 0: no uptake, Grade I: uptake less than the liver but more than background, Grade II: uptake equal to the liver, and Grade III: uptake more than the liver. A total of eight patients of TENIS who had undergone 177Lu-DOTATATE were retrieved. Among those eight patients, the follow-up duration (from the time of the 1st PRRT cycle) at the time of analysis ranged from 7 to 52 months, with an average of 34 months. At the time of assessment, two (25%) out of the eight patients had expired due to extensive metastatic disease and 6 (75%) were alive. On symptomatic response, complete disappearance of symptoms was found in one patient (12.5%), whereas three patients (37.5%) showed partial improvement in symptoms after PRRT and four patients (50%) showed worsening of and appearance of new symptoms. On biochemical response, reduction in serum thyroglobulin (TG) was found in three patients (37.5%) after PRRT and increase in serum TG was noticed in the rest of five patients (62.5%). Imaging response showed stable scan in two patients (25%) and progressive disease (PD) in six patients (75%), following a progression-free survival ranging from 7 to 16 months, when they were considered for tyrosine kinase inhibitors in view of PD. There was no obvious evidence of Grade III/IV hematological or renal toxicity in any of the patients, suggesting that the therapy in this group of patients is well tolerated. In addition, we also observed that most patients of TENIS showed low-grade uptake on SSTR-based imaging (Grade II as per our semi-quantitative scale), with only one patient showing Grade III uptake. 177Lu-DOTATATE PRRT demonstrates modest response in SSTR-positive metastatic TENIS patients: (i) low SSTR expression and tracer avidity, and correspondingly lesser degree of targeting by the therapeutic agent and (ii) the fact that most of the TENIS patients usually have fluorodeoxyglucose (FDG)-avid disease, where high FDG avidity is commensurate with aggressive biology and could be the reason for the relatively less response documented. Larger prospective data need to be accrued in this domain in view of its well tolerability and nonavailability of better efficacious and less toxic treatment at present; however, this needs to be tried in receptor-positive cases with high-grade uptake (Score III/IV) for a definitive conclusion.
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Affiliation(s)
- Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai, Maharashtra, India.,Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Rahul V Parghane
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai, Maharashtra, India.,Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Chinna Naik
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai, Maharashtra, India.,Homi Bhabha National Institute, Mumbai, Maharashtra, India
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16
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Eusebi LH, Thorburn D, Toumpanakis C, Frazzoni L, Johnson G, Vessal S, Luong TV, Caplin M, Pereira SP. Endoscopic ultrasound-guided fine-needle aspiration vs fine-needle biopsy for the diagnosis of pancreatic neuroendocrine tumors. Endosc Int Open 2019; 7:E1393-E1399. [PMID: 31673610 PMCID: PMC6805236 DOI: 10.1055/a-0967-4684] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 06/03/2019] [Indexed: 02/07/2023] Open
Abstract
Background and study aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) as a method of obtaining preoperative diagnosis of pancreatic neuroendocrine tumors (PanNETs) has been reported in several series. Fine-needle biopsies (FNB) are increasingly employed to obtain core specimens during EUS. However, the differences in efficacy between these sampling methods in the diagnosis of PanNETs still needs to be defined. Patients and methods Over a 13-year period, all patients who underwent EUS-guided tissue sampling of suspicious pancreatic lesions with clinical, endoscopic and pathologic details were entered into an electronic database. Lesions underwent EUS-FNA or FNB sampling, or a combination of the two. The accuracy and safety of different EUS-guided sampling methods for confirmed PanNETs were investigated. Results A total of 91 patients (M/F: 42/49, median age: 57 years), who underwent 102 EUS procedures had a final diagnosis of PanNET. Both EUS-guided sampling modalities were used in 28 procedures, EUS-FNA alone was used in 61 cases, while EUS-FNB alone in 13 cases. Diagnostic yield of EUS-FNA and EUS-FNB alone, including the inadequate specimens, was 77.5 % (95 %CI: 68.9 - 86.2 %) and 85.4 % (95 %CI: 74.6 - 96.2 %), respectively. The combination of both sampling modalities established the diagnosis in 96.4 % of cases (27/28) (95 %CI: 89.6 - 100 %), significantly superior to EUS-FNA alone ( P = 0.023). Diagnostic sensitivity among the adequate samples for EUS-FNA, EUS-FNB and for the combination of the two methods was 88.4 % (95 %CI: 80.9 - 96.0 %), 94.3 % (95 %CI: 86.6 - 100 %) and 100 % (95 %CI: 100 - 100 %). There was one reported complication, a post-FNA bleeding, treated conservatively. Conclusions EUS-FNB improves diagnostic sensitivity and confers additional information to cytological assessment of PanNETs.
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Affiliation(s)
- Leonardo H. Eusebi
- HPB endoscopy unit, Royal Free Hospital NHS Trust, London, UK,Department of Medical and Surgical Sciences, University of Bologna, Italy
| | | | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Trust, London, UK
| | - Leonardo Frazzoni
- Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Gavin Johnson
- HPB endoscopy unit, Royal Free Hospital NHS Trust, London, UK,Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Sheida Vessal
- HPB endoscopy unit, Royal Free Hospital NHS Trust, London, UK
| | - Tu Vinh Luong
- Department of Cellular Pathology, Royal Free London NHS Foundation, London, UK
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, Royal Free Hospital NHS Trust, London, UK
| | - Stephen P. Pereira
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK,Institute for Liver & Digestive Health, University College London, UK,Corresponding author Prof. Stephen P. Pereira The UCL Institute for Liver & Digestive HealthNW3 2PFUK+4407729632540
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17
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Walczyk J, Sowa-Staszczak A. Diagnostic imaging of gastrointestinal neuroendocrine neoplasms with a focus on ultrasound. J Ultrason 2019; 19:228-235. [PMID: 31807329 PMCID: PMC6856780 DOI: 10.15557/jou.2019.0034] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Accepted: 06/26/2019] [Indexed: 12/12/2022] Open
Abstract
The diagnosis of gastrointestinal neuroendocrine neoplasms represents a significant diagnostic challenge since these tumours have a various, often non-specific clinical presentation. Currently, more than half of gastroenteropancreatic neuroendocrine neoplasms are detected incidentally, usually during surgery, diagnostic imaging studies or endoscopic procedures performed for other indications. Sometimes the first symptom of the disease is the presence of metastatic lesions in the liver. A neuroendocrine tumour is diagnosed based on the clinical presentation, assessment of specific and non-specific biochemical markers, imaging studies and histopathological examination. Focal lesions, both primary and metastatic may be small and often have an atypical location. Diagnostic imaging of neuroendocrine tumours is of fundamental importance for determining the location of the primary lesion, staging of the disease, selection of treatment and monitoring of its effects. In addition, diagnostic imaging make it possible not only to detect tumours, but also to perform therapeutic procedures based on the result. Transabdominal ultrasound is one of the first diagnostic imaging method for neuroendocrine neoplasms. New ultrasound techniques such as ultrasound elastography, contrast-enhanced ultrasound, endoscopic ultrasound, intraductal and intraoperative ultrasound improve the efficacy of ultrasound examination. Endoscopic ultrasound is a fundamental diagnostic tool for the detection of neuroendocrine tumours of the pancreas and the distal part of the colon. Due to the large variety of neuroendocrine tumours and differences in tumour biology, clinical stage and expression of somatostatin receptors, no single imaging method is sufficient; therefore, in order to determine the right diagnosis and select the best treatment, it is recommended that a combined morphological and functional assessment be used.
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Affiliation(s)
- Joanna Walczyk
- Clinical Department of Endocrinology, University Hospital in Kraków, Kraków, Poland.,Jagiellonian University, Medical College, Faculty of Medicine, Kraków, Poland
| | - Anna Sowa-Staszczak
- Clinical Department of Endocrinology, University Hospital in Kraków, Kraków, Poland.,Jagiellonian University, Medical College, Faculty of Medicine, Kraków, Poland
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18
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Fard N, Schlemmer HP, Raue F, Jobke B. CT- and ultrasound-characteristics of hepatic lesions in patients with multiple endocrine neoplasia syndrome. A retrospective image review of 25 cases. PLoS One 2019; 14:e0212865. [PMID: 30817772 PMCID: PMC6394931 DOI: 10.1371/journal.pone.0212865] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 02/11/2019] [Indexed: 11/18/2022] Open
Abstract
Introduction Liver metastases from neuroendocrine tumors in multiple endocrine neoplasia syndrome are common (75%) and significantly impairs the prognosis. Characterisation of liver lesions in these patients is challenging, as liver metastases are difficult to differentiate from benign liver lesions such as haemangioma. Methods In this study we aimed to characterize the radiological findings of hepatic metastases in MEN patients. The findings of contrast-enhanced CT were considered for the main diagnosis. We retrospectively evaluated 25 patients with MEN-syndrome (10 MEN1/ 15 MEN2) including 11 men and 14 women between 28–62 years of age. Results Liver metastases (48%, 12/25) and hemangioma (40%, 10/25) were the most common liver lesions among our patients. The most common primary tumors in our MEN1 and MEN2 patients with liver metastases were of pancreatic neuroendocrine tumor (70%, 7/10) und medullary thyroid carcinoma (100%, 15/15) origin, respectively. CT-characteristics were grouped into three main categories, depending on contrast dynamics. The majority of hepatic metastases (75%, 14/25) are presented as multiple lesions with a slow growth in an average 5 years of follow-up-period. We were able to find a common CT pattern and categorise these for each MEN-syndrome. Hepatic metastases in MEN1 presented commonly a blurred arterial enhancement with a low portal venous enhancement and less frequently a prominent enhancement in the arterial phase, which mimics the classical haemangioma. In MEN2 the liver metastases exhibited disseminated mixed hyper- and hypo-enhanced lesions in CT-scans. Moreover, lesion calcifications are pathognomonic in MEN2. The main limitation of this study is the missing histopathological confirmation in the majority of cases. Conclusions In this retrospective imaging study, we were able to categorise and find a common CT pattern for hepatic lesions in patients with MEN-syndrome. In order to differentiate these lesions sufficiently, a combination of a 3-phasic CT-scan with US is required. Other liver specific imaging modalities (MRI, CEUS, SMS-PET/CT) should complement the diagnosis in individual cases.
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Affiliation(s)
- Nassim Fard
- Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | | | - Björn Jobke
- Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Telemedicine Clinic/Unilabs, Barcelona, Spain
- * E-mail:
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19
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Parghane RV, Talole S, Basu S. Prevalence of hitherto unknown brain meningioma detected on 68Ga-DOTATATE positron-emission tomography/computed tomography in patients with metastatic neuroendocrine tumor and exploring potential of 177Lu-DOTATATE peptide receptor radionuclide therapy as single-shot treatment approach targeting both tumors. World J Nucl Med 2019; 18:160-170. [PMID: 31040748 PMCID: PMC6476244 DOI: 10.4103/wjnm.wjnm_39_18] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
There is a relative paucity of data in the literature regarding the prevalence of meningiomas and their detection in the clinical setting of neuroendocrine tumors (NETs). The primary aim of this study was to study incidentally detected meningiomas (on 68Ga-DOTATATE/ 18F fluorodeoxyglucose positron-emission tomography/computed tomography [18F-FDG PET/CT]) in metastatic NET patients referred for peptide receptor radionuclide therapy (PRRT). The secondary aims of this study were to evaluate the response rate of these incidentally detected meningiomas following PRRT and determine progression-free survival (PFS) in this group of patients. This was a retrospective analysis of 500 metastatic/advanced NET patients who had undergone 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT before PRRT workup. The case records were searched to identify cases of hitherto unknown meningiomas detected on PET images; subsequently, these patients underwent brain magnetic resonance imaging (MRI) for confirmation of diagnosis. Following 177Lu-DOTATATE PRRT, posttreatment functional and structural imaging response evaluation of the meningiomas were undertaken by 68Ga-DOTATATE PET/CT, MRI, or CT brain, respectively, along with clinical neurological evaluation. The patients were designated as responders and nonresponders based on predefined response assessment criteria. The PFS of these incidentally detected meningiomas following PRRT was estimated using the Kaplan-Meier product-limit method. Twelve NET patients were retrospectively identified with abnormal focal brain uptake on 68Ga-DOTATATE PET/CT. Of these, meningiomas were finally diagnosed on brain MRI examination in six patients (M: F =3:3; age range: 30-66 years; and mean age: 45 years), with a prevalence of 1.2%. Standardized uptake value (SUVmax) of meningiomas on 68Ga-DOTATATE and 18F-FDG PET/CT ranged from 7.0 to 22.0 (average 17.0) and 10.19-13.70 (mean: 12.10), respectively, and lesion-to-normal brain parenchyma SUVmax ratio ranged from 140 to 400 (mean: 340) and 1.02-1.07 (mean: 1.04), respectively. Of six patients with incidentally detected meningiomas, one patient died within 1 month and five patients received 177Lu-DOTATATE PRRT, the number of cycles ranging from two to six (average: 4) and cumulative therapeutic dose ranging from 13.28 to 29.97GBq (average dose: 19.86GBq). Follow-up in these patients ranged from 8 to 36 months (mean: 19.4 months) after the first dose of PRRT. Complete disappearance of neurological symptoms was found in two of five patients (40%), partial response in one of five (20%), and worsening of symptoms in two of five patients (40%). The overall "responder" and "nonresponder" of the meningiomas after PRRT were three patients (60%) and two patients (40%), respectively. Two patients (40%) died of advanced NET at the time of analysis of these data. The observed mean PFS of the meningioma lesions following PRRT was 26.25 months (95% confidence interval, 16.65-35.84 months). No major hematological and renal toxicity were documented in any of these patients. To conclude, 68Ga-DOTATATE PET/CT imaging is an effective technique for the incidental identification of meningioma in NET patients. Considering the limited therapeutic options in the palliative setting of advanced or metastatic NET patients and morbidity associated with the therapeutic procedures, PRRT could be a promising targeted therapeutic approach for such cases of incidentally detected meningiomas, which is also helpful in stabilizing the disease process without any significant toxicity.
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Affiliation(s)
- Rahul V Parghane
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Mumbai, Maharashtra, India.,Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sanjay Talole
- Homi Bhabha National Institute, Mumbai, Maharashtra, India.,Department of Biostatistcs, Tata Memorial Hospital, Mumbai, Maharashtra, India
| | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Mumbai, Maharashtra, India.,Homi Bhabha National Institute, Mumbai, Maharashtra, India
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20
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Abstract
Neuroendocrine tumors, including carcinoids, are rare and insidiously growing tumors. Related to their site of origin, tumors can be functional, causing various forms of the carcinoid syndrome, owing to the overproduction of serotonin, histamine, or other bioactive substances. They often invade adjacent structures or metastasize to the liver and elsewhere. Treatment includes multimodal approaches, including cytoreductive surgery, locoregional embolization, cytotoxic therapy, peptide receptor radionuclide therapy, and various targeted therapies with goals of symptom relief and control of tumor growth. This article summarizes current and emerging approaches to management and reviews several promising future therapies.
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Affiliation(s)
- Paul Benjamin Loughrey
- Department of Ophthalmology, Royal Victoria Hospital, Belfast Trust, Grosvenor Road, Belfast, BT12 6BA, UK; Department of Endocrinology and Diabetes, Royal Victoria Hospital, Belfast Trust, Grosvenor Road, Belfast, BT12 6BA, UK
| | - Dongyun Zhang
- Department of Medicine, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA
| | - Anthony P Heaney
- Department of Medicine, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA; Department of Neurosurgery, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA.
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21
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Affiliation(s)
- Arturo Chiti
- Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano
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22
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Role of Functional Imaging in the Diagnosis of Neuroendocrine Tumors. Updates Surg 2018. [DOI: 10.1007/978-88-470-3955-1_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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23
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Yordanova A, Eppard E, Kürpig S, Bundschuh RA, Schönberger S, Gonzalez-Carmona M, Feldmann G, Ahmadzadehfar H, Essler M. Theranostics in nuclear medicine practice. Onco Targets Ther 2017; 10:4821-4828. [PMID: 29042793 PMCID: PMC5633297 DOI: 10.2147/ott.s140671] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The importance of personalized medicine has been growing, mainly due to a more urgent need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for specific molecular targeting, both for diagnostics and therapy. The visualization of potential targets can help predict if a patient will benefit from a particular treatment. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents has been continually increasing. In this article, important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with a well-known radioiodine therapy in patients with thyroid cancer and then progresses through various approaches for the treatment of advanced cancer with targeted therapies. The aim of this review was to provide a summary of background knowledge and current applications, and to identify the advantages of targeted therapies and imaging in nuclear medicine practices.
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Affiliation(s)
- Anna Yordanova
- Department of Nuclear Medicine (Clinical Nuclear Medicine)
| | | | | | | | | | | | - Georg Feldmann
- Department of Medicine 3, University Hospital Bonn, Bonn, Germany
| | | | - Markus Essler
- Department of Nuclear Medicine (Clinical Nuclear Medicine)
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24
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Manguso N, Gangi A, Johnson J, Harit A, Nissen N, Jamil L, Lo S, Wachsman A, Hendifar A, Amersi F. The role of pre-operative imaging and double balloon enteroscopy in the surgical management of small bowel neuroendocrine tumors: Is it necessary? J Surg Oncol 2017; 117:207-212. [PMID: 28940412 DOI: 10.1002/jso.24825] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 08/11/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES Pre-operative localization of small bowel neuroendocrine tumors (SBNET) is important for operative planning. The aim was to determine the effectiveness of pre-operative imaging and double-balloon enteroscopy (DBE) in identifying extent of disease. METHODS Database review identified 85 patients with primary SBNET between 2006 and 2013. Analysis included patients who underwent imaging, endoscopy, and surgery at our institution. RESULTS Average age was 60.7 years. Sixty-six (77.1%) patients had a primary NET in the ileum. Seventy-two patients (67.3%) underwent CT, 47 (46.7%) had MRI, 44 (46.7%) had somatostatin receptor imaging (SRI), and 41 (39.3%) underwent DBE. The sensitivity of each in identifying the NET was 59.7% for CT, 54% for MRI, 56% for SRI, and 88.1% for DBE. Eighteen (21.2%) patients had primary tumors not identified on imaging. Of these 18, 13 underwent DBE, and 12 of 13 (92.3%) DBEs identified the primary lesion. DBE was significantly better at identifying the primary NET than CT, MRI or SRI (P = 0.004, 0.007, and 0.012). CONCLUSIONS Most SBNETs are identified with a combination of imaging modalities. In those with unidentified primary tumors after imaging, DBE should be considered as it may provide valuable information as to the location of the primary tumor.
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Affiliation(s)
- Nicholas Manguso
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Alexandra Gangi
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Jeffrey Johnson
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Attiya Harit
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Nicholas Nissen
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
| | - Laith Jamil
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Simon Lo
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Ashley Wachsman
- Department of Radiology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Andrew Hendifar
- Department of Internal Medicine, Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, California
| | - Farin Amersi
- Department of Surgery, Division of Surgical Oncology and Hepatobiliary Surgery, Cedars-Sinai Medical Center, Los Angeles, California
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Lolli I, Stasi E, Fucilli F, Pirrelli M, Armentano R, Campanella G, Lotesoriere C, Lorusso D. Sarcoidosis mimicking metastatic progression of pancreatic neuroendocrine tumor: A case report. Medicine (Baltimore) 2017; 96:e7273. [PMID: 28658123 PMCID: PMC5500045 DOI: 10.1097/md.0000000000007273] [Citation(s) in RCA: 2] [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] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Pancreatic neuroendocrine tumors (PNETs) account for less than 5% of all pancreatic tumors. PNETs develop from pancreatic endocrine islet cells and have a variable range of malignant potential. These neoplasms tend to have a slower growth rate than exocrine tumors and may remain undetectable for years. Achieving a correct diagnosis and staging is of key importance for the optimal management of the disease and requires experience with the disease, an accurate clinical status evaluation and a critical interpretation of the radiological findings derived from morphological and functional imaging techniques as well as an integrated multidisciplinary approach. The possibility that some clinical data and radiological findings encountered during the diagnostic and staging procedures may not be related to PNETs but to concomitant clinical conditions should always be taken into consideration. This is mandatory as an incorrect stadiation may lead to patients' mis-management. PATIENT CONCERNS We report the case of a 34-year-old female, with a past medical history of idiopathic acute pancreatitis, presenting with a severe upper abdominal pain, steady and radiating to the back. DIAGNOSES Initial investigations incidentally detected a nonfunctioning pancreatic neuroendocrine tumor (NF-PNET) of intermediate grade G2. Subsequent investigations aimed at determining a correct tumor staging showed a negative indium-111- OctreoScan but an increased 18F-labeled fluorodesossiglucose (18F-FDG) uptake in multiple bilateral nodules in the lungs and in 1 nodular lesion located in the right gluteal subcutaneous tissue. An early tumor progression of a G2 NF-PNET that had to be treated with chemotherapy was suspected. INTERVENTIONS The histological examination of the gluteal subcutaneous nodule showed noncaseating granulomas, disproving the initial clinical suspect and allowing the diagnosis of active sarcoidosis in the G2 NF-PNET patient. LESSONS A misdiagnosis and a consequent therapeutic mismanagement were avoided with the support of an integrated multidisciplinary team.
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Affiliation(s)
| | | | | | | | | | | | | | - Dionigi Lorusso
- Department of Surgery, Scientific Institute for Digestive Disease IRCCS Saverio De Bellis, Castellana Grotte (Ba), Italy
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Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F–DOPA. Eur J Nucl Med Mol Imaging 2017; 44:1588-1601. [DOI: 10.1007/s00259-017-3728-y] [Citation(s) in RCA: 150] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Accepted: 05/09/2017] [Indexed: 12/15/2022]
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Pelosi E, Deandreis D, Cassalia L, Penna D. Diagnostic Applications of Nuclear Medicine: Colorectal Cancer. NUCLEAR ONCOLOGY 2017:777-797. [DOI: 10.1007/978-3-319-26236-9_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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28
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Bodei L, Kidd M, Gilardi L, Volterrani D, Paganelli G, Grana CM, Modlin IM. Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors. NUCLEAR ONCOLOGY 2017:799-838. [DOI: 10.1007/978-3-319-26236-9_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Maxwell JE, Howe JR. Pancreatic neuroendocrine tumors. BLUMGART'S SURGERY OF THE LIVER, BILIARY TRACT AND PANCREAS, 2-VOLUME SET 2017:997-1006.e3. [DOI: 10.1016/b978-0-323-34062-5.00065-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Dromain C, Déandréis D, Scoazec JY, Goere D, Ducreux M, Baudin E, Tselikas L. Imaging of neuroendocrine tumors of the pancreas. Diagn Interv Imaging 2016; 97:1241-1257. [PMID: 27876341 DOI: 10.1016/j.diii.2016.07.012] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 07/18/2016] [Indexed: 12/13/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous disease. PNET can be functioning or non-functioning with different clinical presentations and different prognosis based on WHO and pTNM classifications. The role of imaging includes the localization of small functioning tumor, differentiation of these tumors from adenocarcinoma, identification of signs of malignancy and evaluation of extent. PNETs have a broad spectrum of appearance. On CT and MRI, most of functioning PNETs are well defined small tumors with intense and homogeneous enhancement on arterial and portal phases. However, some PNETs with a more fibrous content may have a more delayed enhancement that is best depicted on the delayed phase. Other PNETs can present as purely cystic, complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are larger with less intense and more heterogeneous enhancement. Functional imaging is useful for disease staging, to detect disease recurrence or the primary but also to select patient candidate for peptide receptor radiometabolic treatment. Somatostatin receptor scintigraphy (SRS) (Octreoscan®) is still the most available technique. Gallium 68-SST analogue PET have been demonstrated to be more sensitive than SRS-SPEC and it will be the future of functional imaging for NET. Finally, 18FDG PET/CT is indicated for more aggressive PNET as defined either by negative SRS and huge tumor burden or ki67 above 10% or poorly differentiated PNEC tumors.
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Affiliation(s)
- C Dromain
- Service de radiodiagnostic et radiologie interventionnelle, bureau CIBM 09-084, rue Bugnon 46, 1011 Lausanne, Switzerland.
| | - D Déandréis
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - J-Y Scoazec
- Anapathology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - D Goere
- Surgery department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - M Ducreux
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - E Baudin
- Oncology department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
| | - L Tselikas
- Imaging department, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94805 Villejuif cedex, France
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Liu EH, Solorzano CC, Katznelson L, Vinik AI, Wong R, Randolph G. AACE/ACE disease state clinical review: diagnosis and management of midgut carcinoids. Endocr Pract 2016; 21:534-545. [PMID: 25962092 DOI: 10.4158/ep14464.dsc] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE Neuroendocrine tumors (NETs) are a collection of complex tumors that arise from the diffuse endocrine system, primarily from the digestive tract. Carcinoid tumors most commonly originate from the small intestine. These tumors are either referred to as small intestinal neuroendocrine tumors or midgut carcinoids (MGCs). The purpose of this review article is to survey the diagnostic and therapeutic pathways for patients with MGC and provide an overview of the complex multidisciplinary care involved in improving their quality of life, treatment outcomes, and survival. METHODS The current literature regarding the diagnosis and management of MGCs was reviewed. RESULTS Dry flushing and secretory diarrhea are the hallmarks of the clinical syndrome of MGC. Managing MGC requires attention to the overall symptom complex, including the physical effects of the tumor and biomarker levels. The somatostatin analogs (SAs) octreotide and lanreotide are highly efficacious for symptomatic improvement. MGCs require resection to encompass the primary tumor and mesenteric lymph node metastases and should include cholecystectomy if the patient is likely to receive SA therapy. Debulking of liver metastasis by resection in combination with ablative therapies and other liver-directed modalities may help palliate symptoms and hormonal overproduction in carefully selected patients. Quality of life is an important measure of patients' perception of the burden of their disease and impact of treatment modalities and may be a useful guide in deciding changes in therapy to alter apparent health status. CONCLUSION MGC is a challenging malignancy that requires the input of a multidisciplinary team to develop the best treatment plan. Consultation with expert centers that specialize in NETs may also be indicated for complex cases. With expert care, patients can be cured or live with the disease and enjoy good quality of life.
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Affiliation(s)
- Eric H Liu
- Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University, Nashville, Tennessee
| | - Carmen C Solorzano
- Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University, Nashville, Tennessee
| | | | - Aaron I Vinik
- Department of Medicine, Eastern Virginia Medical School, Norfolk, Virginia
| | - Richard Wong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Gregory Randolph
- Department of Otolaryngology, Massachusetts General Hospital, Boston, Massachusetts
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Jilesen A, Hoefnagel S, Busch O, Bennink R, Gouma D, Nieveen van Dijkum E. The influence of somatostatin receptor scintigraphy during preoperative staging of non-functioning pancreatic neuroendocrine tumours. Clin Radiol 2016; 71:537-42. [PMID: 27016111 DOI: 10.1016/j.crad.2016.01.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 01/11/2016] [Accepted: 01/18/2016] [Indexed: 11/30/2022]
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El Rassy E, Tabchi S, Kourie HR, Assi T, Chebib R, Farhat F, Kattan J. Pancreatic small cell cancer. Clin Res Hepatol Gastroenterol 2016; 40:276-280. [PMID: 26566245 DOI: 10.1016/j.clinre.2015.09.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/15/2015] [Accepted: 09/24/2015] [Indexed: 02/04/2023]
Abstract
Small cell carcinoma (SCC) is most commonly associated with lung cancer. Extra-pulmonary SCC can originate in virtually any organ system, with the gastrointestinal tract being the most common site of involvement. We review the clinical presentation, pathogenesis, histology, imaging modalities and optimal therapeutic management of PSCC in light of available evidence.
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Affiliation(s)
- Elie El Rassy
- Department of Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Lebanon, Lebanon.
| | - Samer Tabchi
- Department of Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Lebanon, Lebanon
| | - Hampig Raphael Kourie
- Department of Oncology, Jules Bordet Institute, Free University of Brussels (ULB), 1, Héger-Bordet Street, Brussels, Belgium
| | - Tarek Assi
- Department of Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Lebanon, Lebanon
| | - Ralph Chebib
- Department of Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Lebanon, Lebanon
| | - Fadi Farhat
- Department of Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Lebanon, Lebanon
| | - Joseph Kattan
- Department of Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Lebanon, Lebanon
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Deppen SA, Liu E, Blume JD, Clanton J, Shi C, Jones-Jackson LB, Lakhani V, Baum RP, Berlin J, Smith GT, Graham M, Sandler MP, Delbeke D, Walker RC. Safety and Efficacy of 68Ga-DOTATATE PET/CT for Diagnosis, Staging, and Treatment Management of Neuroendocrine Tumors. J Nucl Med 2016; 57:708-14. [PMID: 26769865 DOI: 10.2967/jnumed.115.163865] [Citation(s) in RCA: 162] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 12/01/2015] [Indexed: 12/13/2022] Open
Abstract
UNLABELLED Our purpose was to evaluate the safety and efficacy of (68)Ga-DOTATATE PET/CT compared with (111)In-pentetreotide imaging for diagnosis, staging, and restaging of pulmonary and gastroenteropancreatic neuroendocrine tumors. METHODS (68)Ga-DOTATATE PET/CT and (111)In-pentetreotide scans were obtained for 78 of 97 consecutively enrolled patients with known or suspected pulmonary or gastroenteropancreatic neuroendocrine tumors. Safety and toxicity were measured by comparing vital signs, serum chemistry values, or acquisition-related medical complications before and after (68)Ga-DOTATATE injection. Added value was determined by changes in treatment plan when (68)Ga-DOTATATE PET/CT results were added to all prior imaging, including (111)In-pentetreotide. Interobserver reproducibility of (68)Ga-DOTATATE PET/CT scan interpretation was measured between blinded and nonblinded interpreters. RESULTS (68)Ga-DOTATATE PET/CT and (111)In-pentetreotide scans were significantly different in impact on treatment (P < 0.001). (68)Ga-DOTATATE PET/CT combined with CT or liver MRI changed care in 28 of 78 (36%) patients. Interobserver agreement between blinded and nonblinded interpreters was high. No participant had a trial-related event requiring treatment. Mild, transient events were tachycardia in 1, alanine transaminase elevation in 1, and hyperglycemia in 2 participants. No clinically significant arrhythmias occurred. (68)Ga-DOTATATE PET/CT correctly identified 3 patients for peptide-receptor radiotherapy incorrectly classified by (111)In-pentetreotide. CONCLUSION (68)Ga-DOTATATE PET/CT was equivalent or superior to (111)In-pentetreotide imaging in all 78 patients. No adverse events requiring treatment were observed. (68)Ga-DOTATATE PET/CT changed treatment in 36% of participants. Given the lack of significant toxicity, lower radiation exposure, and improved accuracy compared with (111)In-pentetreotide, (68)Ga-DOTATATE imaging should be used instead of (111)In-pentetreotide imaging where available.
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Affiliation(s)
- Stephen A Deppen
- Veterans Affairs Hospital, Tennessee Valley VA Healthcare System, Nashville, Tennessee Department of Thoracic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Eric Liu
- Rocky Mountain Cancer Centers, Denver, Colorado
| | - Jeffrey D Blume
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jeffrey Clanton
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Chanjuan Shi
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Laurie B Jones-Jackson
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | | | - Richard P Baum
- THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging (PET/CT), ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany
| | - Jordan Berlin
- Vanderbilt-Ingram Cancer Center, Nashville, Tennessee; and
| | - Gary T Smith
- Veterans Affairs Hospital, Tennessee Valley VA Healthcare System, Nashville, Tennessee Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Michael Graham
- Department of Radiology, University of Iowa, Iowa City, Iowa
| | - Martin P Sandler
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Dominique Delbeke
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Ronald C Walker
- Veterans Affairs Hospital, Tennessee Valley VA Healthcare System, Nashville, Tennessee Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee Vanderbilt-Ingram Cancer Center, Nashville, Tennessee; and
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Maxwell JE, O'Dorisio TM, Howe JR. Biochemical Diagnosis and Preoperative Imaging of Gastroenteropancreatic Neuroendocrine Tumors. Surg Oncol Clin N Am 2015; 25:171-94. [PMID: 26610781 DOI: 10.1016/j.soc.2015.08.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Neuroendocrine tumors are a group of neoplasms that can arise in a variety of locations throughout the body and often metastasize early. A patient's only chance for cure is surgical removal of the primary tumor and all associated metastases, although even when surgical cure is unlikely, patients can benefit from surgical debulking. A thorough preoperative workup will often require multiple clinical tests and imaging studies to locate the primary tumor, delineate the extent of the disease, and assess tumor functionality. This review discusses the biomarkers important for the diagnosis of these tumors and the imaging modalities needed.
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Affiliation(s)
- Jessica E Maxwell
- Department of General Surgery, University of Iowa Hospitals and Clinics, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - Thomas M O'Dorisio
- Department of Internal Medicine, University of Iowa Hospitals and Clinics, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
| | - James R Howe
- Department of General Surgery, University of Iowa Hospitals and Clinics, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
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Abstract
Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed.
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Maxwell JE, Howe JR. Imaging in neuroendocrine tumors: an update for the clinician. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2015; 2:159-168. [PMID: 26257863 DOI: 10.2217/ije.14.40] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Neuroendocrine tumors are a heterogeneous group of neoplasms that are best worked up and managed using a variety of clinical and imaging studies. They are often diagnosed after they have already metastasized, though this does not necessarily preclude an attempt at curative surgical treatment or surgical debulking. Tumor burden assessment often requires use of multiple imaging modalities including computed tomography, magnetic resonance imaging and ultrasound. Somatostatin receptor-based imaging is also of great utility in looking for primaries and determining the extent of metastatic disease. This paper will review the most common imaging modalities used in the diagnosis and treatment of neuroendocrine tumors.
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Affiliation(s)
- Jessica E Maxwell
- Department of General Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
| | - James R Howe
- Department of General Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
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Bodei L, Sundin A, Kidd M, Prasad V, Modlin IM. The status of neuroendocrine tumor imaging: from darkness to light? Neuroendocrinology 2015; 101:1-17. [PMID: 25228173 DOI: 10.1159/000367850] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 08/23/2014] [Indexed: 11/19/2022]
Abstract
Diagnostic imaging plays a pivotal role in the diagnosis, staging, treatment selection and follow-up for neuroendocrine tumors. The available diagnostic strategies are morphologic imaging, including computed tomography, magnetic resonance imaging (MRI) and ultrasound techniques, and molecular imaging, including scintigraphy with (111)In-pentetreotide and positron emission tomography with (68)Ga-DOTA-peptides, (18)F-DOPA and (11)C-5-HTP. A combination of anatomic and functional techniques is routinely performed to optimize sensitivity and specificity. The introduction of diffusion-weighted MRI and dynamic contrast-enhanced techniques represents a promising advance in radiologic imaging, whereas new receptor-binding peptides, including somatostatin agonists and antagonists, represent the recent most favorable innovation in molecular imaging. Future development includes the short-term validation of these techniques, but in extension also a more comprehensive multilevel integration of biologic information pertaining to a specific tumor and patient, possibly encompassing genomic considerations, currently evolving as a new entity denoted 'precision medicine'. The ideal is a diagnostic sequence that captures the global status of an individual's tumor and encompasses a multidimensional characterization of tumor location, metabolic performance and target identification. To date, advances in imagery have focused on increasing resolution, discrimination and functional characterization. In the future, the fusion of imagery with the parallel analysis of biological and genomic information has the potential to considerably amplify diagnosis.
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Affiliation(s)
- Lisa Bodei
- Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy
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Yang J, Kan Y, Ge BH, Yuan L, Li C, Zhao W. Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis. Acta Radiol 2014; 55:389-98. [PMID: 23928010 DOI: 10.1177/0284185113496679] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gallium-68 somatostatin receptor positron emission tomography (PET) has been used in the diagnosis of neuroendocrine tumors (NETs). The compounds often used in molecular imaging of NETs with PET are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. There is varying affinity to different somatostatin receptors. PURPOSE To systematically review and perform a meta-analysis of published data regarding the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. MATERIAL AND METHODS A comprehensive literature search of studies published through 30 April 2013 regarding 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs was performed using the PubMed/MEDLINE, Embase, and Scopus databases. Pooled sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. RESULTS Ten studies comprising 416 patients with NETs were included in this meta-analysis. The pooled sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs calculated on a per-patient-based analysis was 93% (95% confidence interval [CI] 89-96%) and 96% (95% CI 91-99%). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing NETs was 85% (95% CI 74-93%) and 100% (95% CI 82-100%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98, respectively, on a per-patient-based analysis. CONCLUSION The molecular imaging agents 68Ga-DOTATOC and 68Ga-DOTATATE demonstrated high sensitivity and specificity in the diagnosis of NETs on PET scan. Although both are accurate tools in the diagnosis of NETs, 68Ga-DOTATATE PET may be more sensitive and specific than 68Ga-DOTATOC PET scan.
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Affiliation(s)
- Jigang Yang
- Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Ying Kan
- Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Benjamin H Ge
- Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Leilei Yuan
- Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Chunlin Li
- Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, PR China
| | - Wenrui Zhao
- Department of Nuclear Medicine, Navy General Hospital, Hai Dian District, PR China
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Woodbridge LR, Murtagh BM, Yu DFQC, Planche KL. Midgut Neuroendocrine Tumors: Imaging Assessment for Surgical Resection. Radiographics 2014; 34:413-26. [DOI: 10.1148/rg.342135504] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Sollini M, Erba PA, Fraternali A, Casali M, Di Paolo ML, Froio A, Frasoldati A, Versari A. PET and PET/CT with 68gallium-labeled somatostatin analogues in Non GEP-NETs Tumors. ScientificWorldJournal 2014; 2014:194123. [PMID: 24693229 PMCID: PMC3947736 DOI: 10.1155/2014/194123] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2013] [Accepted: 10/30/2013] [Indexed: 12/27/2022] Open
Abstract
Somatostatin (SST) is a 28-amino-acid cyclic neuropeptide mainly secreted by neurons and endocrine cells. A major interest for SST receptors (SSTR) as target for in vivo diagnostic and therapeutic purposes was born since a series of stable synthetic SST-analouges PET became available, being the native somatostatin non feasible for clinical use due to the very low metabolic stability. The rationale for the employment of SST-analogues to image cancer is both based on the expression of SSTR by tumor and on the high affinity of these compounds for SSTR. The primary indication of SST-analogues imaging is for neuroendocrine tumors (NETs), which usually express a high density of SSTR, so they can be effectively targeted and visualized with radiolabeled SST-analogues in vivo. Particularly, SST-analogues imaging has been widely employed in gastroenteropancreatic (GEP) NETs. Nevertheless, a variety of tumors other than NETs expresses SSTR thus SST-analogues imaging can also be used in these tumors, particularly if treatment with radiolabeled therapeutic SST-analouges PET is being considered. The aim of this paper is to provide a concise overview of the role of positron emission tomography/computed tomography (PET/CT) with (68)Ga-radiolabeled SST-analouges PET in tumors other than GEP-NETs.
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Affiliation(s)
- Martina Sollini
- Nuclear Medicine Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Paola Anna Erba
- Regional Center of Nuclear Medicine, University of Pisa, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, 56125 Pisa, Italy
| | - Alessandro Fraternali
- Nuclear Medicine Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Massimiliano Casali
- Nuclear Medicine Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Maria Liberata Di Paolo
- Nuclear Medicine Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Armando Froio
- Nuclear Medicine Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Andrea Frasoldati
- Endocrinology Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, 42123 Reggio Emilia, Italy
| | - Annibale Versari
- Nuclear Medicine Unit, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, 42123 Reggio Emilia, Italy
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van Essen M, Sundin A, Krenning EP, Kwekkeboom DJ. Neuroendocrine tumours: the role of imaging for diagnosis and therapy. Nat Rev Endocrinol 2014; 10:102-14. [PMID: 24322649 DOI: 10.1038/nrendo.2013.246] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
In patients with neuroendocrine tumours (NETs), a combination of morphological imaging and nuclear medicine techniques is mandatory for primary tumour visualization, staging and evaluation of somatostatin receptor status. CT and MRI are well-suited for discerning small lesions that might escape detection by single photon emission tomography (SPECT) or PET, as well as for assessing the local invasiveness of the tumour or the response to therapy. Somatostatin receptor imaging, by (111)In-pentetreotide scintigraphy or PET with (68)Ga-labelled somatostatin analogues, frequently identifies additional lesions that are not visible on CT or MRI scans. Currently, somatostatin receptor scintigraphy with (111)In-pentetreotide is the more frequently available of the two techniques to determine somatostatin receptor expression and is needed to select patients for peptide receptor radionuclide therapy. In the future, because of its higher sensitivity, PET with (68)Ga-labelled somatostatin analogues is expected to replace somatostatin receptor scintigraphy. Whereas (18)F-FDG-PET is only used in high-grade neuroendocrine cancers, PET-CT with (18)F-dihydroxy-L-phenylalanine or (11)C-5-hydroxy-L-tryptophan is a useful problem-solving tool and could be considered for the evaluation of therapy response in the future. This article reviews the role of imaging for the diagnosis and management of intestinal and pancreatic NETs. Response evaluation and controversies in NET imaging will also be discussed.
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Affiliation(s)
- Martijn van Essen
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
| | - Anders Sundin
- Department of Radiology, Karolinska University Hospital, Stockholm, 17176 Stockholm, Sweden
| | - Eric P Krenning
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
| | - Dik J Kwekkeboom
- Department of Nuclear Medicine, Erasmus MC, 's Gravendijkwal 230, Rotterdam, 3015 GD, Netherlands
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Ganeshan D, Bhosale P, Yang T, Kundra V. Imaging features of carcinoid tumors of the gastrointestinal tract. AJR Am J Roentgenol 2013; 201:773-786. [PMID: 24059366 DOI: 10.2214/ajr.12.9758] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Recent studies have provided a better understanding of the biologic behavior of gastrointestinal carcinoid tumors. This article focusing on imaging of gastrointestinal carcinoids will emphasize epidemiology, molecular biology, taxonomy, histopathology, and management. CONCLUSION Gastrointestinal carcinoids are a biologically heterogeneous group of tumors, with variable clinical presentation and biologic behavior. Imaging can play an important role in multidisciplinary identification and management of this disease.
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Affiliation(s)
- Dhakshina Ganeshan
- 1 All authors: Division of Diagnostic Imaging, Body Imaging Section, Unit 1473, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009
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Abstract
Pancreatic neuroendocrine neoplasms are uncommon but rising in incidence. There have been recent changes in the WHO nomenclature and a newly proposed American Joint Committee on Cancer TNM staging, which complement each other. These neoplasms are of great medical and radiological interest because of their diverse presenting features and imaging appearances. There is an increased role for both anatomic and functional imaging in the assessment of these neoplasms. A review of the nomenclature, staging, and imaging is presented in this paper.
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Single photon emission computed tomography/computed tomography in the evaluation of neuroendocrine tumours: a review of the literature. Nucl Med Commun 2013; 34:98-107. [PMID: 23222696 DOI: 10.1097/mnm.0b013e32835bd59d] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
The scintigraphic investigation of neuroendocrine tumours such as carcinoids has depended on standard techniques such as I-metaiodobenzylguanidine and In-pentetreotide imaging. More recently, the use of PET techniques such as Ga-DOTATATE has been advocated. An alternative improved modality is high-quality single photon emission computed tomography/computed tomography (SPECT/CT), which has the advantages of better sensitivity and specificity and has shown improved localization in up to 60% of cases. These advantages are especially true for pancreatic and lymph node lesions. Overall, SPECT/CT can result in a change in clinical management in 25% of patients. Although it is possible to combine SPECT and CT performed at different time points, there is better anatomical localization and improved reporter confidence when SPECT and CT are performed simultaneously.
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Somatostatin receptor PET/CT in neuroendocrine tumours: update on systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 2013; 40:1770-80. [PMID: 23873003 DOI: 10.1007/s00259-013-2482-z] [Citation(s) in RCA: 145] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Accepted: 06/03/2013] [Indexed: 12/14/2022]
Abstract
PURPOSE Neuroendocrine tumours (NET) are uncommon and may be localized in many different places in the body. Traditional imaging has mainly been performed with CT and somatostatin receptor scintigraphy (SRS). Recently, it has become possible to use somatostatin receptor PET/CT (SMSR PET) instead, which might improve diagnostic quality. To evaluate the diagnostic quality of SMSR PET we performed a meta-analysis as an update of a previous study published in 2012. METHODS A literature search was performed searching MEDLINE, Embase and five other databases with a combination of the expressions "PET", "positron emission tomography", "neuroendocrine" and "NET". The search was updated to 31 December 2012. Studies were selected which evaluated the sensitivity and specificity of SMSR PET for NET in the thorax or abdomen with a study size of at least eight patients. The methodological quality of the included studies was evaluated with QUADAS-2. RESULTS Eight studies fulfilled the inclusion criteria and were selected for final analysis, and 14 articles from a previous meta-analysis were added for a total of 22 articles. A total of 2,105 patients were included in the studies, an increase from 567 in the previous meta-analysis. The pooled sensitivity was 93 % (95 % CI 91 - 94 %) and specificity 96 % (95 % CI 95 - 98 %). The area under the summary ROC curve was 0.98 (95 % CI 0.95 - 1.0). In the previous meta-analysis the pooled sensitivity was 93 % (95 % CI 91 - 95 %) and specificity 91 % (95 % CI 82 - 97 %). CONCLUSION SMSR PET has good diagnostic performance for evaluation of NET in the thorax and abdomen, better than SRS which has been the previous standard method. This meta-analysis gives further support for switching to SMSR PET.
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Puli SR, Kalva N, Bechtold ML, Pamulaparthy SR, Cashman MD, Estes NC, Pearl RH, Volmar FH, Dillon S, Shekleton MF, Forcione D. Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: a systematic review and meta analysis. World J Gastroenterol 2013; 19:3678-84. [PMID: 23801872 PMCID: PMC3691045 DOI: 10.3748/wjg.v19.i23.3678] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2013] [Revised: 04/06/2013] [Accepted: 04/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To detect pancreatic neuroendocrine tumors (PNETs) has been varied. This study is undertaken to evaluate the accuracy of endoscopic ultrasound (EUS) in detecting PNETs. METHODS Only EUS studies confirmed by surgery or appropriate follow-up were selected. Articles were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model). RESULTS Initial search identified 2610 reference articles, of these 140 relevant articles were selected and reviewed. Data was extracted from 13 studies (n = 456) which met the inclusion criteria. Pooled sensitivity of EUS in detecting a PNETs was 87.2% (95%CI: 82.2-91.2). EUS had a pooled specificity of 98.0% (95%CI: 94.3-99.6). The positive likelihood ratio of EUS was 11.1 (95%CI: 5.34-22.8) and negative likelihood ratio was 0.17 (95%CI: 0.13-0.24). The diagnostic odds ratio, the odds of having anatomic PNETs in positive as compared to negative EUS studies was 94.7 (95%CI: 37.9-236.1). Begg-Mazumdar bias indicator for publication bias gave a Kendall's tau value of 0.31 (P = 0.16), indication no publication bias. The P for χ² heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION EUS has excellent sensitivity and specificity to detect PNETs. EUS should be strongly considered for evaluation of PNETs.
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PET/CT using ¹⁸F-FDOPA provides improved staging of carcinoid tumor patients in a Canadian setting. Nucl Med Commun 2012; 33:322-30. [PMID: 22183015 DOI: 10.1097/mnm.0b013e32834f2603] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
AIM In Canada, staging of carcinoid tumors is largely based on computed tomography (CT) imaging sometimes complemented with somatostatin receptor scintigraphy (SRS). This study assessed the diagnostic accuracy of 6-[¹⁸F]fluoro-3,4-dihydroxyphenylalanine (¹⁸F-FDOPA) PET/CT in neuroendocrine tumors. METHODS We prospectively included 27 patients with either suspected carcinoid (n=6, with all prior tests negative) or with an established diagnosis of intestinal carcinoid tumor (n=21) from two Canadian treatment centers. Findings of ¹⁸F-FDOPA PET/CT were compared with SRS, CT, and combined SRS/CT using a composite reference standard comprising all available imaging, biochemistry, surgery, and follow-up data. Sensitivity was calculated per patient, per body region, and per lesion. The contribution to patient management was estimated from the feedback of attending physicians. RESULTS In documented carcinoid patients, ¹⁸F-FDOPA PET/CT identified disease in 20 of 21 patients (patient-based sensitivity 95%). In 56 positive regions, ¹⁸F-FDOPA PET/CT detected 53, CT detected 34, SRS detected 34, and CT+SRS detected 39 regions, leading to region-based sensitivities of 95, 61, 62, and 71%, respectively. Lesion-based sensitivities were 96, 69, 50, and 72%, respectively. In the six patients with suspected disease only, one CT scan was positive, but ¹⁸F-FDOPA PET/CT was negative for all. ¹⁸F-FDOPA PET contributed to patient management in 12/21 patients (57%). CONCLUSION ¹⁸F-FDOPA PET/CT proved to be an excellent modality for staging of carcinoid tumor patients, with superior performance compared with currently applied methods in Canada. In patients with suspected disease with negative prior imaging investigations, ¹⁸F-FDOPA was not helpful.
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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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Pepe G, Moncayo R, Bombardieri E, Chiti A. Somatostatin receptor SPECT. Eur J Nucl Med Mol Imaging 2012; 39 Suppl 1:S41-51. [DOI: 10.1007/s00259-011-2019-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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