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Perez K, Del Rivero J, Kennedy EB, Basu S, Chauhan A, Connolly HM, Dasari AN, Gangi A, Clarke CN, Hallet J, Howe JR, Grady E, Ivanidze J, Mittra ES, White SB, Raj NP, Vijayvergia N, Lewis MA, Chan JA, Kunz PL, Mailman J, Arshad J, Soares HP, Singh S, Chandrasekharan C, Soulen MC, Janson ET, Halfdanarson TR, Strosberg JR, Bergsland EK. Symptom Management for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline. JCO Oncol Pract 2025:OP2500133. [PMID: 40344544 DOI: 10.1200/op-25-00133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/07/2025] [Accepted: 03/24/2025] [Indexed: 05/11/2025] Open
Abstract
PURPOSE To develop a clinical practice guideline and recommendations for symptom management of patients with well-differentiated grade 1 to grade 3 metastatic gastroenteropancreatic neuroendocrine tumors. METHODS ASCO convened an Expert Panel to develop a clinical practice guideline by reviewing the literature for relevant guidelines, systematic reviews, randomized controlled trials (RCTs), and observational studies to develop recommendations for clinical practice. RESULTS The literature review identified eight guidelines, 19 systematic reviews, and three RCTs that informed the development of guideline recommendations. RECOMMENDATIONS Recommendations are included for carcinoid syndrome, carcinoid heart disease and carcinoid crisis, and functional pancreatic neuroendocrine tumor syndromes. Recommendations are provided for surgical management, liver-directed therapy, and systemic therapy options, as well as palliative care. Limited guidance is provided for sequencing of interventions.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
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Affiliation(s)
| | | | | | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Parel, Mumbai, India
| | | | | | | | | | | | - Julie Hallet
- Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | | | | | | | | | | | - Nitya P Raj
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | | | | | | | | | - Simron Singh
- Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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Guo Z, Chen Y, Liu R, Chen Y. The Occult Insulinoma Was Localized Using Endoscopic Ultrasound Guidance: A Case Report. Clin Case Rep 2025; 13:e9634. [PMID: 39935661 PMCID: PMC11810623 DOI: 10.1002/ccr3.9634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 09/23/2024] [Accepted: 11/11/2024] [Indexed: 02/13/2025] Open
Abstract
Insulinomas are the primary etiology of endogenous hyperinsulinemic hypoglycemia, which often manifest with Whipple's triad and neuroglycopenic symptoms. Given the diverse clinical manifestation and subtle onset of insulinomas generally in a small size, detecting a minority of these generally small tumors can be challenging. We reported a case of a 44-year-old female patient with recurrent hypoglycemia accompanied by hyperinsulinemia, and the conventional imaging revealed no abnormality. With the aid of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB), the insulinoma was precisely diagnosed and localized, and successfully excised via operation. The patient's hyperinsulinemia and hypoglycemic episodes were relieved significantly after surgery. The application of EUS-FNAB notably enhances the diagnostic accuracy for occult insulinomas, thereby informing appropriate surgical management. Herein, we advocate for invasive EUS examination in patients exhibiting strong clinical and laboratory indicators of insulinoma, even when conventional imaging results are negative.
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Affiliation(s)
- Zhongqiu Guo
- Department of Endocrinology and Metabolism, Longgang District People's Hospital of ShenzhenThe Second Affiliated Hospital of the Chinese University of Hong Kong, Longgang Central CityShenzhenGuangdongPeople's Republic of China
| | - Yanrong Chen
- Department of Endocrinology and Metabolism, Longgang District People's Hospital of ShenzhenThe Second Affiliated Hospital of the Chinese University of Hong Kong, Longgang Central CityShenzhenGuangdongPeople's Republic of China
| | - Ronghuo Liu
- Department of Endocrinology and Metabolism, Longgang District People's Hospital of ShenzhenThe Second Affiliated Hospital of the Chinese University of Hong Kong, Longgang Central CityShenzhenGuangdongPeople's Republic of China
| | - Yuhua Chen
- Department of Endocrinology and Metabolism, Longgang District People's Hospital of ShenzhenThe Second Affiliated Hospital of the Chinese University of Hong Kong, Longgang Central CityShenzhenGuangdongPeople's Republic of China
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3
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Nduwimana MJ, Colak C, Bilgin C, Kassmeyer BA, Bolan CM, Menias CO, Venkatesh SK. Differentiation between renal cell carcinoma metastases to the pancreas and pancreatic neuroendocrine tumors in patients with renal cell carcinoma on CT or MRI. Abdom Radiol (NY) 2025:10.1007/s00261-024-04787-7. [PMID: 39775027 DOI: 10.1007/s00261-024-04787-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/23/2024] [Accepted: 12/24/2024] [Indexed: 01/11/2025]
Abstract
PURPOSE To determine whether renal cell carcinoma metastases (RCC-Mets) to the pancreas can be differentiated from pancreatic neuroendocrine tumors (PNETs) in patients with RCC on CT or MRI at presentation. METHODS This retrospective study included patients with biopsy-proven RCC-Mets (n = 102) or PNETs (n = 32) at diagnosis or after nephrectomy for RCC. Inter-observer agreement (Cohen kappa) was assessed in 95 patients with independent reads by two radiologists, with discrepancies resolved by consensus for final analysis. The remaining 39 cases underwent consensus reads by two different radiologists for final analysis. The CT/MRI images were reviewed for number, size, regional distribution, parenchymal location (exophytic or intrapancreatic), contrast-enhancement, and enhancement pattern of pancreatic lesions in the available phases. Statistical tests were conducted using two sample t-tests and Pearson's chi-squared test for numeric and categorical variables respectively. RESULTS The study group comprised of 134 patients (90 males) with 265 lesions (229 RCC-Mets and 36 PNETs). Patients with PNETs were significantly younger (62 ± 12 years vs. 67 ± 9 years, p = 0.013). Inter-observer agreement for CT/MRI features was excellent across multiple imaging variables (k = 0.86-1.00). Most PNETs were single lesions (88 vs. 63%, p = 0.008), smaller in size (14 mm vs. 23 mm, p = 0.042), more common in the body and tail (81 vs. 57%, p = 0.01), showed homogeneous contrast enhancement (64-79% vs. 39-49%, p < 0.01-0.03), less T1-hypointense (80 vs. 99%, p = 0.002) and more DWI hyperintense (71 vs. 58%, p < 0.001) compared to RCC-Mets. CONCLUSION PNETs are typically single, occur in distal pancreas, and enhance homogeneously compared to RCC-Mets which are often multiple, occur in the proximal pancreas, and enhance heterogeneously.
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Affiliation(s)
| | | | - Cem Bilgin
- Mayo Clinic Rochester, Rochester, MN, USA
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Hesami M, Blake M, Anderson MA, Asmundo L, Kilcoyne A, Najmi Z, Caravan PD, Catana C, Czawlytko C, Esfahani SA, Kambadakone AR, Samir A, McDermott S, Domachevsky L, Ursprung S, Catalano OA. Diagnostic Anatomic Imaging for Neuroendocrine Neoplasms: Maximizing Strengths and Mitigating Weaknesses. J Comput Assist Tomogr 2024; 48:521-532. [PMID: 38657156 PMCID: PMC11245376 DOI: 10.1097/rct.0000000000001615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
ABSTRACT Neuroendocrine neoplasms are a heterogeneous group of gastrointestinal and lung tumors. Their diverse clinical manifestations, variable locations, and heterogeneity present notable diagnostic challenges. This article delves into the imaging modalities vital for their detection and characterization. Computed tomography is essential for initial assessment and staging. At the same time, magnetic resonance imaging (MRI) is particularly adept for liver, pancreatic, osseous, and rectal imaging, offering superior soft tissue contrast. The article also highlights the limitations of these imaging techniques, such as MRI's inability to effectively evaluate the cortical bone and the questioned cost-effectiveness of computed tomography and MRI for detecting specific gastric lesions. By emphasizing the strengths and weaknesses of these imaging techniques, the review offers insights into optimizing their utilization for improved diagnosis, staging, and therapeutic management of neuroendocrine neoplasms.
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Affiliation(s)
- Mina Hesami
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Michael Blake
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Mark A. Anderson
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Luigi Asmundo
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
- Postgraduation School in Radiodiagnostics, Università degli Studi di Milano, Milan, Italy
| | - Aoife Kilcoyne
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Zahra Najmi
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Peter D. Caravan
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ciprian Catana
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Cynthia Czawlytko
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shadi Abdar Esfahani
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Avinash R. Kambadakone
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Anthony Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shaunagh McDermott
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Liran Domachevsky
- Department of Nuclear Medicine, The Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Stephan Ursprung
- Department of Radiology, University Hospital Tuebingen, Tuebingen, Germany
| | - Onofrio A. Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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5
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Ferreira Dalla Pria HR, Sharbidre KG, Virarkar M, Javadi S, Bhosale H, Maxwell J, Lall C, Morani AC. Imaging Update for Hereditary Abdominopelvic Neuroendocrine Neoplasms. J Comput Assist Tomogr 2024; 48:533-544. [PMID: 37832535 DOI: 10.1097/rct.0000000000001547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2023]
Abstract
ABSTRACT Neuroendocrine neoplasms have shown a linear increase in incidence and prevalence in recent decades, primarily due to improved cross-sectional imaging, expanded use of endoscopic procedures, and advanced genetic analysis. However, diagnosis of hereditary neuroendocrine tumors is still challenging because of heterogeneity in their presentation, the variety of tumor locations, and multiple associated syndromes. Radiologists should be familiar with the spectrum of these tumors and associated hereditary syndromes. Furthermore, as the assessment of multiple tumor elements such as morphology, biochemical markers, and presence of metastatic disease are essential for the treatment plan, conventional anatomic and functional imaging methods are fundamental in managing and surveilling these cases. Our article illustrates the role of different cross-sectional imaging modalities in diagnosing and managing various hereditary abdominopelvic neuroendocrine tumors.
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Affiliation(s)
| | - Kedar G Sharbidre
- Abdominal Imaging Section, Department of Radiology, University of Alabama at Birmingham, AL
| | - Mayur Virarkar
- Department of Radiology, University of Florida College of Medicine-Jacksonville, FL
| | - Sanaz Javadi
- Department of Abdominal Imaging, Division of Diagnostic Imaging
| | | | - Jessica Maxwell
- Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Chandana Lall
- Department of Radiology, University of Florida College of Medicine-Jacksonville, FL
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Mo S, Huang C, Wang Y, Zhao H, Wu W, Jiang H, Qin S. Endoscopic ultrasonography-based intratumoral and peritumoral machine learning radiomics analyses for distinguishing insulinomas from non-functional pancreatic neuroendocrine tumors. Front Endocrinol (Lausanne) 2024; 15:1383814. [PMID: 38952387 PMCID: PMC11215175 DOI: 10.3389/fendo.2024.1383814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 06/05/2024] [Indexed: 07/03/2024] Open
Abstract
OBJECTIVES To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs). METHODS A total of 106 patients, comprising 61 with insulinomas and 45 with NF-PNETs, were included in this study. The patients were randomly assigned to either the training or test cohort. Radiomics features were extracted from both the intratumoral and peritumoral regions, respectively. Six machine learning algorithms were utilized to train intratumoral prediction models, using only the nonzero coefficient features. The researchers identified the most effective intratumoral radiomics model and subsequently employed it to develop peritumoral and combined radiomics models. Finally, a predictive nomogram for insulinomas was constructed and assessed. RESULTS A total of 107 radiomics features were extracted based on EUS, and only features with nonzero coefficients were retained. Among the six intratumoral radiomics models, the light gradient boosting machine (LightGBM) model demonstrated superior performance. Furthermore, a peritumoral radiomics model was established and evaluated. The combined model, integrating both the intratumoral and peritumoral radiomics features, exhibited a comparable performance in the training cohort (AUC=0.876) and achieved the highest accuracy in predicting outcomes in the test cohorts (AUC=0.835). The Delong test, calibration curves, and decision curve analysis (DCA) were employed to validate these findings. Insulinomas exhibited a significantly smaller diameter compared to NF-PNETs. Finally, the nomogram, incorporating diameter and radiomics signature, was constructed and assessed, which owned superior performance in both the training (AUC=0.929) and test (AUC=0.913) cohorts. CONCLUSION A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.
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Affiliation(s)
- Shuangyang Mo
- Gastroenterology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
- Gastroenterology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Cheng Huang
- Oncology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Yingwei Wang
- Gastroenterology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Huaying Zhao
- Gastroenterology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Wenhong Wu
- Gastroenterology Department, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, China
| | - Haixing Jiang
- Gastroenterology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Shanyu Qin
- Gastroenterology Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Khoury T, Sbeit W, Fusaroli P, Campana D, Brighi N, Napoleon B, Lisotti A. Safety and efficacy of endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine neoplasms: Systematic review and meta-analysis. Dig Endosc 2024; 36:395-405. [PMID: 37702096 DOI: 10.1111/den.14681] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 09/10/2023] [Indexed: 09/14/2023]
Abstract
OBJECTIVE Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been constantly increasing, particularly in the treatment of pancreatic neuroendocrine neoplasms (pNENs). While emerging data in this field are accumulating, we aimed to assess the pooled efficacy and safety of EUS-RFA for pNENs. METHODS The PubMed/Medline, Embase, and Cochrane Library databases search was conducted to identify studies reporting EUS-RFA of pNENs with outcomes of interest (efficacy and safety). The primary outcome was radiological response. Efficacy was assessed by the pooled clinical response rate, whereas safety was assessed by the pooled adverse events (AEs) rate. Heterogeneity was assessed using I2. Pooled estimates and the 95% confidence interval (CI) were calculated using a random-effect model. RESULTS Eleven studies involving 292 patients were included. The pooled technical success rate was 99.2% (95% CI 97.9-99.9%), with no heterogeneity. The pooled complete radiological response was 87.1% (95% CI 80.1-92.8%). The pooled partial response was 11.4% (95% CI 6.2-18.1%). The pooled clinical response rate for functional pNENs was 94.9% (95% CI 90.7-97.9%), with no heterogeneity. The pooled incidence of AEs was 20.0% (95% CI 14.0-26.7%); most AEs were mild to moderate in grade, while the pooled incidence of severe AEs was 0.9% (95% CI 0.2-2.3%). The most common AEs were transient mild abdominal pain in 19 patients (6.5%), and mild to moderate pancreatitis in 23 patients (7.9%). No cases of mortality were reported. CONCLUSION Endoscopic ultrasound-guided radiofrequency ablation resulted on a feasible approach for pNENs treatment, with excellent technical success, high radiological and clinical response, and acceptable AE rate.
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Affiliation(s)
- Tawfik Khoury
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Wisam Sbeit
- Department of Gastroenterology, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Pietro Fusaroli
- Gastroenterology Unit, Hospital of Imola, University of Bologna, Bologna, Italy
| | - Davide Campana
- Department of Experimental, Diagnostic and Specialty Medicine, Sant'Orsola-Malpighi University Hospital, ENETS Center of Excellence, Bologna, Italy
| | - Nicole Brighi
- Department of Medical Oncology, IRCCS Romagna Institute for the Study of Tumors "Dino Amadori", Meldola, Italy
| | - Bertrand Napoleon
- Department of Gastroenterology, Jean Mermoz Private Hospital, Ramsay Health, Lyon, France
| | - Andrea Lisotti
- Gastroenterology Unit, Hospital of Imola, University of Bologna, Bologna, Italy
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Ferreira B, Heredia A, Serpa J. An integrative view on glucagon function and putative role in the progression of pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC). Mol Cell Endocrinol 2023; 578:112063. [PMID: 37678603 DOI: 10.1016/j.mce.2023.112063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Revised: 08/16/2023] [Accepted: 09/02/2023] [Indexed: 09/09/2023]
Abstract
Cancer metabolism research area evolved greatly, however, is still unknown the impact of systemic metabolism control and diet on cancer. It makes sense that systemic regulators of metabolism can act directly on cancer cells and activate signalling, prompting metabolic remodelling needed to sustain cancer cell survival, tumour growth and disease progression. In the present review, we describe the main glucagon functions in the control of glycaemia and of metabolic pathways overall. Furthermore, an integrative view on how glucagon and related signalling pathways can contribute for pancreatic neuroendocrine tumours (pNETs) and hepatocellular carcinomas (HCC) progression, since pancreas and liver are the major organs exposed to higher levels of glucagon, pancreas as a producer and liver as a scavenger. The main objective is to bring to discussion some glucagon-dependent mechanisms by presenting an integrative view on microenvironmental and systemic aspects in pNETs and HCC biology.
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Affiliation(s)
- Bárbara Ferreira
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal
| | - Adrián Heredia
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal; Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz MB, 1649-028, Lisboa, Portugal
| | - Jacinta Serpa
- iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Campo Dos Mártires da Pátria, 130, 1169-056, Lisboa, Portugal; Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG), Rua Prof Lima Basto, 1099-023, Lisboa, Portugal.
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Gorai PK, Bharti PS, Kumar S, Rajacharya GH, Bandyopadhyay S, Pal S, Dhingra R, Kumar R, Nikolajeff F, Kumar S, Rani N. C1QA and COMP: plasma-based biomarkers for early diagnosis of pancreatic neuroendocrine tumors. Sci Rep 2023; 13:21021. [PMID: 38030709 PMCID: PMC10686980 DOI: 10.1038/s41598-023-48323-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/24/2023] [Indexed: 12/01/2023] Open
Abstract
Pancreatic Neuroendocrine tumors (PanNET) are challenging to diagnose and often detected at advanced stages due to a lack of specific and sensitive biomarkers. This study utilized proteomics as a valuable approach for cancer biomarker discovery; therefore, mass spectrometry-based proteomic profiling was conducted on plasma samples from 12 subjects (3 controls; 5 Grade I, 4 Grade II PanNET patients) to identify potential proteins capable of effectively distinguishing PanNET from healthy controls. Data are available via ProteomeXchange with the identifier PXD045045. 13.2% of proteins were uniquely identified in PanNET, while 60% were commonly expressed in PanNET and controls. 17 proteins exhibiting significant differential expression between PanNET and controls were identified with downstream analysis. Further, 5 proteins (C1QA, COMP, HSP90B1, ITGA2B, and FN1) were selected by pathway analysis and were validated using Western blot analysis. Significant downregulation of C1QA (p = 0.001: within groups, 0.03: control vs. grade I, 0.0013: grade I vs. grade II) and COMP (p = 0.011: within groups, 0.019: control vs grade I) were observed in PanNET Grade I & II than in controls. Subsequently, ELISA on 38 samples revealed significant downregulation of C1QA and COMP with increasing disease severity. This study shows the potential of C1QA and COMP in the early detection of PanNET, highlighting their role in the search for early-stage (Grade-I and Grade-II) diagnostic markers and therapeutic targets for PanNET.
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Affiliation(s)
- Priya Kumari Gorai
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
| | | | - Shashi Kumar
- Department of Metabolic Engineering, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | - Girish H Rajacharya
- Department of Metabolic Engineering, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
| | | | - Sujoy Pal
- Department of GI Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Renu Dhingra
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Fredrik Nikolajeff
- Department of Health Science, Lulea University of Technology, Luleå, Sweden
| | - Saroj Kumar
- Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
- Department of Health Science, Lulea University of Technology, Luleå, Sweden.
| | - Neerja Rani
- Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
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Alshareefy Y, Cummins S, Mazzoleni A, Sharma V, Guggilapu S, Leong AWY, Wireko AA. A review of functional pancreatic neuroendocrine tumors: Exploring the molecular pathogenesis, diagnosis and treatment. Medicine (Baltimore) 2023; 102:e36094. [PMID: 37986400 PMCID: PMC10659674 DOI: 10.1097/md.0000000000036094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 10/13/2023] [Accepted: 10/23/2023] [Indexed: 11/22/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PanNETs) are a rare subtype of pancreatic cancer and can be divided into functional (30-40%) and nonfunctional subtypes. The different subtypes of functional PanNETs (F-PanNETs) have a variety of classical presentations that raise suspicion for an underlying PanNET. It is estimated that 90% of PanNETs are sporadic, and the PI3K-Akt-mTOR and ATRX/DAXX signaling pathways have been recognized as key genetic pathways implicated in the pathogenesis. The other 10% of PanNETs may occur in the context of familial cancer syndromes such as MEN1. Chromogranin A is the most useful biomarker currently; however, several studies have shown limitations with its use, especially its prognostic value. Synaptophysin is a novel biomarker which has shown promising preliminary results however its use clinically has yet to be established. Blood tests assessing hormone levels, cross-sectional imaging, and endoscopic ultrasound remain at the core of establishing a diagnosis of F-PanNET. The treatment options for F-PanNETs include surgical methods such as enucleation, systemic therapies like chemotherapy and novel targeted therapies such as everolimus. The prognosis for F-PanNETs is more favorable than for nonfunctional PanNETs, however metastatic disease is associated with poor survival outcomes. Researchers should also focus their efforts on identifying novel pathways implicated in the pathogenesis of F-PanNETs in order to develop new targeted therapies that may reduce the need for surgical intervention and on the establishment of novel biomarkers that may reduce the need for invasive testing and allow for earlier detection of F-PanNETs.
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Affiliation(s)
- Yasir Alshareefy
- School of Medicine, Trinity College Dublin, The University of Dublin, Ireland
| | - Sinead Cummins
- School of Medicine, Trinity College Dublin, The University of Dublin, Ireland
| | - Adele Mazzoleni
- Barts and the London School of Medicine and Dentistry, London, United Kingdom
| | - Vidushi Sharma
- School of Medicine, Trinity College Dublin, The University of Dublin, Ireland
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11
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Damaskos C, Dimitroulis D, Garmpi A, Antoniou EA, Kouraklis G, Psilopatis I, Mavri M, Diamantis E, Marinos G, Kyriakos G, Farmaki P, Patsouras A, Kontzoglou K, Garmpis N. Synchronous Insulinoma and Glucagonoma: A Review of the Literature. In Vivo 2023; 37:2402-2408. [PMID: 37905620 PMCID: PMC10621456 DOI: 10.21873/invivo.13345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 08/03/2023] [Accepted: 08/07/2023] [Indexed: 11/02/2023]
Abstract
BACKGROUND/AIM Pancreatic neuroendocrine tumors (PNETs) are pancreatic neoplasms with neuroendocrine features, divided into functioning and non-functioning. The non-functioning PNETs are the largest group, and their morbidity is the result of their potential to invade surrounding tissues and metastasize. The functioning PNETs produce hormonal symptoms due to over-secretion of specific hormones. They constitute 1% to 2% of all pancreatic tumors. The use of novel imaging methods has rendered their detection more frequent. Insulinoma, the most common functioning PNET, comprises 35-40% of all functioning PNETs. Its clinical presentation is due to hyperinsulinemia and the subsequent hypoglycemia. Glucagonoma accounts for 5% of all PNETs and is the fourth most frequent functioning PNET, following insulinoma, gastrinoma, and vipoma. Its symptoms are due to the massive secretion of glucagon and ensuing hyperglycemia. The co-existence of two PNETs is a very rare entity. This report aimed to describe cases of concomitant insulinomas and glucagonomas. MATERIALS AND METHODS A review of the literature was performed using the PubMed database and Cochrane library aiming to identify reported cases of concomitant pancreatic insulinoma and glucagonoma. Specifically, the research was conducted using the keywords, separately and in various combination, including insulinoma, glucagonoma, cystic, pancreatic neuroendocrine tumors and hypoglycemia. Only publications in English were included in the present study. RESULTS A total of 8 cases of concomitant pancreatic insulinoma and glucagonoma were identified, corresponding to the period 1992-2021. CONCLUSION Concomitant insulinoma and glucagonoma are rare and challenging. A multidisciplinary approach is necessary for diagnosis, prognosis, and therapy.
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Affiliation(s)
- Christos Damaskos
- Renal Transplantation Unit, Laiko General Hospital, Athens, Greece;
- NS Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Dimitroulis
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Anna Garmpi
- First Department of Propedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Efstathios A Antoniou
- NS Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Department of General Surgery and HPB Surgery of Adults and Children, Hygeia Hospital, Athens, Greece
| | - Gregory Kouraklis
- Department of Surgery, Evgenideio Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Iason Psilopatis
- Department of Gynecology, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Maria Mavri
- Department of General Surgery and HPB Surgery of Adults and Children, Hygeia Hospital, Athens, Greece
| | - Evangelos Diamantis
- Academic Department of Internal Medicine - Endocrinology Unit, Agioi Anargyroi General Oncology Hospital of Kifisia, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Marinos
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Georgios Kyriakos
- Seccion de Endocrinologia y Nutrition, Hospital General Universitario Santa Lucia, Cartagena, Spain
| | - Paraskevi Farmaki
- First Department of Pediatrics, Agia Sofia Children's Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Konstantinos Kontzoglou
- NS Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Nikolaos Garmpis
- NS Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
- Department of General Surgery and HPB Surgery of Adults and Children, Hygeia Hospital, Athens, Greece
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Regolo M, Cardaci N, Salmeri C, Laudani A, Colaci M, Ippolito M, Motta F, Magrì S, Parisi S, Torcitto AG, Malatino L. Pancreatic Neuroendocrine Tumor (Pan-NET) Presented by Abdominal Pain: A Case Report and Literature Review. J Clin Med 2023; 12:6617. [PMID: 37892755 PMCID: PMC10607714 DOI: 10.3390/jcm12206617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 09/24/2023] [Accepted: 10/18/2023] [Indexed: 10/29/2023] Open
Abstract
A pancreatic neuroendocrine tumor (Pan-NET) is a rare neoplasm originating in the neuroendocrine system. Carcinoid syndrome occurs in approximately 19% of patients with functional Pan-NETs, typically when liver metastases occur. In this paper, we describe the case of a patient with a low-grade non-functional Pan-NET, but with a typical clinical presentation of carcinoid syndrome. An 81-year-old male was admitted to our Department of Internal Medicine at Cannizzaro Hospital (Catania, Italy) because of the onset of abdominal pain with nausea, loose stools, and episodic flushing. Firstly, an abdominal contrast-enhanced CT scan showed a small pancreatic hyper-vascular mass; then, a gallium-68 DOTATOC integrated PET/CT revealed an elevated expression of SSTR receptors. Serum chromogranin A and urinary 5-HIAA measurements were negative. We performed an endoscopic ultrasonography (EUS) by a fine-needle biopsy (EUS-FNB), allowing the immunostaining of a small mass (0.8 cm) and the diagnosis of a low-grade (G1) non-functional Pan-NET (NF-Pan-NET). Surgery was waived, while a follow-up strategy was chosen. The early recognition of Pan-NETs, although rare, is necessary to improve the patient's survival. Although helpful to allow for immunostaining, EUS-FNB needs to be warranted in future studies comparing EUS-FNB to EUS-FNA (fine-needle aspiration), which is, to date, reported as the tool of choice to diagnose Pan-NETs.
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Affiliation(s)
- Matteo Regolo
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Nicolas Cardaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Clara Salmeri
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Alfredo Laudani
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Michele Colaci
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
| | - Massimo Ippolito
- Nuclear Medicine Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Fabio Motta
- Pathological Anatomy Unit, Cannizzaro Hospital, 95126 Catania, Italy;
| | - Salvatore Magrì
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | - Stefanie Parisi
- Endoscopy Unit, Cannizzaro Hospital, 95126 Catania, Italy; (S.M.); (S.P.)
| | | | - Lorenzo Malatino
- Department of Clinical and Experimental Medicine, University of Catania, 95124 Catania, Italy; (M.R.); (A.L.); (M.C.)
- Academic Unit of Internal Medicine, Cannizzaro Hospital, 95126 Catania, Italy
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13
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Giampatzis V, Kotsiari C, Bostantzis P, Chrisoulidou A, Fotiadou A, Loti S, Papantoniou S, Papadopoulou P. Pancreatic Vasoactive Intestinal Peptide-Producing Tumor as a Rare Cause of Acute Diarrhea and Severe Hypokalemia. J Med Cases 2023; 14:307-316. [PMID: 37868325 PMCID: PMC10586331 DOI: 10.14740/jmc4141] [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: 07/24/2023] [Accepted: 08/19/2023] [Indexed: 10/24/2023] Open
Abstract
Pancreatic vasoactive intestinal peptide-producing tumor (VIPoma) is a rare functional neuroendocrine tumor most commonly presenting with watery diarrhea and electrolyte abnormalities that include hypokalemia, hypercalcemia and metabolic acidosis. This type of tumor has usually insidious clinical behavior that is characterized by chronic secretory diarrhea, lasting usually from months to years before diagnosis, not responsive to usual medical or dietary treatment approaches. Given the resemblance of VIPoma with other more common causes of chronic watery diarrhea, the final diagnosis is often delayed and the tumors are usually large and metastatic at the time of detection. Our case of pancreatic VIPoma demonstrates an unusual clinical course for this type of tumor with acute refractory diarrhea and rapid deterioration of patient's clinical and biochemical status that required emergent in-hospital diagnosis and treatment. Our patient is a 45-year-old woman who presented with abrupt, watery diarrhea during the past 24 h before admission accompanied with severe hypokalemia as well as hyponatremia, hyperglycemia and hypercalcemia. Despite aggressive management with fluid administration and electrolyte replenishment, no significant improvement in patient's symptoms and electrolyte imbalance was observed. After exclusion of other causes of acute diarrhea from the medical history and the laboratory tests, the clinical suspicion of a functional neuroendocrine tumor was raised. After the establishment of final diagnosis of pancreatic VIPoma with biochemical tests and magnetic resonance imaging (MRI), somatostatin analogues were prescribed and the patient underwent distal pancreatectomy and splenectomy with no signs of lymph node and splenic metastases. Few days after the surgical resection of the tumor, the patient readmitted to our hospital with tarry stools and severe anemia. The abdominal computed tomography (CT) revealed a retroperitoneal cystic lesion. The gastrointestinal bleeding gradually recessed after endoscopic hemostasis of duodenal ulcer lesions whereas the cystic lesion (postoperative lymphocele) was successfully drained under CT-guidance before discharge. After almost 10 years postoperatively, the patient is still asymptomatic with no signs of relapse or metastasis of the disease in the periodic laboratory and imaging follow-up. In conclusion, pancreatic VIPoma can sometimes manifest symptoms of abrupt onset and rapid progression that require high clinical suspicion, appropriate diagnostic workup and aggressive management.
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Affiliation(s)
| | | | | | - Alexandra Chrisoulidou
- Endocrinology Department, Theageneio Anticancer Hospital, Alexandrou Symeonidi 2, Thessaloniki 54639, Greece
| | - Aimilia Fotiadou
- Endocrinology Department, Theageneio Anticancer Hospital, Alexandrou Symeonidi 2, Thessaloniki 54639, Greece
| | - Soultana Loti
- Department of Radiology, General Hospital of Kavala, Greece
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14
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Pellegrino F, Granata V, Fusco R, Grassi F, Tafuto S, Perrucci L, Tralli G, Scaglione M. Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists. Tomography 2023; 9:217-246. [PMID: 36828370 PMCID: PMC9958666 DOI: 10.3390/tomography9010018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/22/2023] [Accepted: 01/23/2023] [Indexed: 01/31/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes. Furthermore, they are primarily nonfunctioning, while, in the case of insulinomas, gastrinomas, glucagonomas, vipomas, and somatostatinomas, they produce hormones responsible for clinical syndromes. The GEP-NEN tumor grade and cell differentiation may result in different clinical behaviors and prognoses, with grade one (G1) and grade two (G2) neuroendocrine tumors showing a more favorable outcome than grade three (G3) NET and neuroendocrine carcinoma. Two critical issues should be considered in the NEN diagnostic workup: first, the need to identify the presence of the tumor, and, second, to define the primary site and evaluate regional and distant metastases. Indeed, the primary site, stage, grade, and function are prognostic factors that the radiologist should evaluate to guide prognosis and management. The correct diagnostic management of the patient includes a combination of morphological and functional evaluations. Concerning morphological evaluations, according to the consensus guidelines of the European Neuroendocrine Tumor Society (ENETS), computed tomography (CT) with a contrast medium is recommended. Contrast-enhanced magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is usually indicated for use to evaluate the liver, pancreas, brain, and bones. Ultrasonography (US) is often helpful in the initial diagnosis of liver metastases, and contrast-enhanced ultrasound (CEUS) can solve problems in characterizing the liver, as this tool can guide the biopsy of liver lesions. In addition, intraoperative ultrasound is an effective tool during surgical procedures. Positron emission tomography (PET-CT) with FDG for nonfunctioning lesions and somatostatin analogs for functional lesions are very useful for identifying and evaluating metabolic receptors. The detection of heterogeneity in somatostatin receptor (SSTR) expression is also crucial for treatment decision making. In this narrative review, we have described the role of morphological and functional imaging tools in the assessment of GEP-NENs according to current major guidelines.
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Affiliation(s)
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Naples, Italy
| | - Francesca Grassi
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80127 Naples, Italy
| | - Salvatore Tafuto
- S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori, IRCCS, Fondazione “G. Pascale”, 80131 Naples, Italy
| | - Luca Perrucci
- Ferrara Department of Interventional and Diagnostic Radiology, Ospedale di Lagosanto, Azienda AUSL, 44023 Ferrara, Italy
| | - Giulia Tralli
- Department of Radiology, Ospedale Santa Maria della Misericordia, 45100 Rovigo, Italy
| | - Mariano Scaglione
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
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15
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Marc B, Monino L, Rimbas M. EUS-guided intra-tumoral therapies. Best Pract Res Clin Gastroenterol 2022; 60-61:101817. [PMID: 36577536 DOI: 10.1016/j.bpg.2022.101817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
EUS-guided treatments for focal tumor lesions has been developed since 20 years using at onset of the technique mainly local and guided alcohol injection [1-4]. Pancreatic tumors are the most assessed targeted lesions for EUS treatment because of their accessibility and because EUS management could be a safe alternative to surgery. More and more pancreatic tumors are discovered mainly fortuitously due to the advances in conventional imaging (abdominal ultrasound, CT, MRI) resulting in the question of surgical management of an asymptomatic pancreatic lesion ("incidentaloma") [5-8]. The lesions detected include mostly pancreatic cystic neoplasms (PCN) and neuroendocrine tumors (NET) mainly well differentiated. Clinically, NET are mostly non-functional and do not induce secretory disorders [5-8]. Once their nature is yielded by diagnostic tests like EUS-FNA, incidental nonfunctional NET currently lead to difficult management when their largest diameter is less than 2 cm [2,4,9,10]. EUS-guided treatment for pancreatic adenocarcinoma have also been developed with recent prospective observational study and randomized control study [11,12]. Thus, therapeutic surgical choices could be challenged by EUS- guided treatment [2,4,9].
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Affiliation(s)
- Barthet Marc
- Aix Marseille Université, Service de Gastro-entérologie, Hôpital Nord, Chemin des Bourrely, 13915, Marseille, cedex 20, France.
| | | | - Mihai Rimbas
- Gastroenterology Department, Colentina Clinical Hospital, Bucharest, Romania
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16
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Persano I, Parlagreco E, La Salvia A, Audisio M, Volante M, Buttigliero C, Scagliotti GV, Brizzi MP. Synchronous or metachronous presentation of pancreatic neuroendocrine tumor versus secondary lesion to pancreas in patients affected by renal cell carcinoma. Systematic review. Semin Oncol 2022; 49:476-481. [PMID: 36759234 DOI: 10.1053/j.seminoncol.2023.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 01/17/2023] [Accepted: 01/17/2023] [Indexed: 02/05/2023]
Abstract
The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two malignancies share both radiological and cytopathological features, making the differential diagnosis very challenging. In this review, we collected all cases of concurrent diagnosis of localized panNET and RCC, with or without VHL, as reported in the literature to date. We aimed to provide an insight into the differential diagnosis between panNET and RCC pancreatic metastasis with a focus on the optimal therapeutic algorithm depending on the diagnosis. We performed literature research in PubMed library databases for articles about coexisting panNET and RCC published from 2001 to 2018. We selected nine articles with a total of 13 patients, including one treated at our institution. Patients' median age was 49 years and eight out of 13 patients were women. VHL was diagnosed in nine cases. Most patients underwent radical nephrectomy for RCC (9/13) and a clear cell renal carcinoma variant was identified in six cases. The diagnosis of panNET was synchronous with RCC detection in nine cases and metachronous in four cases. The diameter of the pancreatic lesion was >2 cm in six cases. In two cases the panNET was misdiagnosed as metastatic RCC by radiological tests. Somatostatin receptor scanning was performed only in our patient (Octreoscan) showing intense uptake in the pancreatic mass. Endoscopic ultrasound fine needle aspiration of the pancreatic lesion was performed in four patients: in two cases the panNET was confused with metastatic RCC by cytological analysis. Most patients underwent pancreatic surgery (10/13) without histological confirmation. Clear cell panNET was recognized in six cases, while mixed neuroendocrine non-neuroendocrine neoplasm was diagnosed in one patient. Immunohistochemistry (IHC) staining showed positivity to typical neuroendocrine markers (chromogranin A and synaptophysin) in all reported tested cases (8/8). Three patients underwent systemic treatment: two patients received sunitinib and one patient interleukin-2 (IL-2). Other neoplasms were observed in seven patients, of whom six were affected by VHL syndrome. When neoplastic lesions are recognized in both the kidney and pancreas, panNET and RCC pancreatic metastasis are often misdiagnosed due to similar radiological and cytopathological features. An accurate differential diagnosis is crucial and IHC plays a central role in distinguishing the two entities. The therapeutic algorithm may change depending on the diagnosis: while pancreatic RCC metastases benefit from resection, in panNETs and VHL the indication for surgery must be carefully evaluated.
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Affiliation(s)
- Irene Persano
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy.
| | - Elena Parlagreco
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
| | - Anna La Salvia
- National Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, Italy
| | - Marco Audisio
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
| | - Marco Volante
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
| | - Consuelo Buttigliero
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
| | | | - Maria Pia Brizzi
- Department of Oncology, University Hospital San Luigi Gonzaga, University of Turin, Orbassano, Italy
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Endoscopic ultrasound-guided radiofrequency ablation of premalignant pancreatic-cystic neoplasms and neuroendocrine tumors: prospective study. Eur J Gastroenterol Hepatol 2022; 34:1111-1115. [PMID: 36170679 DOI: 10.1097/meg.0000000000002422] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a developing therapeutic approach for premalignant pancreatic-cystic neoplasms (PCNs) and small pancreatic neuroendocrine tumors (PNETs). The safety and efficacy of pancreatic EUS-RFA were previously reported in small series. Herein we report our initial experience with RFA of PCNs and small PNETs. METHODS This is a prospective single-center study including 12 patients with a median follow-up of 7 months, with either PCN or PNET &lt;2 cm. Eligible PCNs were either intraductal papillary mucinous neoplasms (IPMN) with worrisome features or mucinous cystic neoplasms (MCN) that were not eligible or refused surgery. Ablation was performed using a 19-gauge dedicated needle. RESULTS Twelve patients were treated, five had PCNs (four IPMNs, one MCN; median size of 36 mm, range 12-60) and seven had PNETs (median size 8.9 mm, range 6-18). Among patients with PCNs, the complete radiologic response was achieved in 3/5 (60%), partial response in 1/5 (20%) and failure in 1/5 (20%). Among six patients with nonfunctioning PNETs, the complete radiologic response was achieved in 4/6 (66.7%), partial radiologic response in 0/6 (0%) and failure in 2/6 (33.3%). Following a median follow-up of 7 months. One patient with insulinoma showed complete resolution of hypoglycemia-related symptoms. Three postprocedural adverse events occurred, including one case (1/12, 8.3%) of mild acute pancreatitis and two cases (2/12, 16.7%) of abdominal pain. CONCLUSION EUS-guided RFA for premalignant PCNs and PNETs is feasible and well-tolerated. Efficacy would be further evaluated with continued follow-up of patients.
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Figueiredo Ferreira M, Garces-Duran R, Eisendrath P, Devière J, Deprez P, Monino L, Van Laethem JL, Borbath I. EUS-guided radiofrequency ablation of pancreatic/peripancreatic tumors and oligometastatic disease: an observational prospective multicenter study. Endosc Int Open 2022; 10:E1380-E1385. [PMID: 36262511 PMCID: PMC9576329 DOI: 10.1055/a-1922-4536] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 08/09/2022] [Indexed: 10/25/2022] Open
Abstract
Background and study aims Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is an emerging and minimally invasive technique that seems promising for treatment of focal pancreatic and peripancreatic lesions. Our aim was to prospectively evaluate the feasibility, safety, and technical and clinical success of pancreatic and extra-pancreatic EUS-RFA. Patients and methods We prospectively collected clinical and technical data for all patients who underwent EUS-RFA at two Belgian academic centers from June 2018 to February 2022. Feasibility, adverse events (AEs), and follow-up were also assessed. Results Twenty-nine patients were included, accounting for 35 lesions: 10 non-functioning neuroendocrine tumors (29 %), 13 pancreatic insulinomas (37 %), one adenocarcinoma (3 %), and 11 intra-pancreatic and extra-pancreatic metastatic lesions (31 %). Technical success was achieved in 100 % of cases, with a median of three power applications per lesion (interquartile range 2). The majority of patients (59 %) presented no collateral effects, three (10.3 %) developed non-severe acute pancreatitis, and four (14 %) had mild abdominal pain. At 6 months follow-up (n = 25), 36 % of patients showed radiological complete response, 16 % presented a significant partial response and 48 % showed < 50 % decrease in diameter. At 12 months (n = 20), 30 % showed complete necrosis and 15 % > 50 % decrease in diameter. Hypoglycemia related to insulinoma was immediately corrected in all 13 cases, with no recurrence during follow-up. Conclusions EUS-RFA is feasible, safe, and effective for treatment of pancreatic and peripancreatic tumors. Larger and longer multicenter prospective studies are warranted to establish its role in management of focal pancreatic lesions and oligometastatic disease. Symptomatic insulinoma currently represent the best indication.
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Affiliation(s)
- Mariana Figueiredo Ferreira
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Belgium,Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Saint-Pierre University Hospital, Université Libre de Bruxelles, Belgium
| | - Rodrigo Garces-Duran
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Cliniques Universitaires St. Luc, Université Catholique de Louvain, Belgium
| | - Pierre Eisendrath
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Saint-Pierre University Hospital, Université Libre de Bruxelles, Belgium
| | - Jacques Devière
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Belgium
| | - Pierre Deprez
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Cliniques Universitaires St. Luc, Université Catholique de Louvain, Belgium
| | - Laurent Monino
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Cliniques Universitaires St. Luc, Université Catholique de Louvain, Belgium
| | - Jean-Luc Van Laethem
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Belgium
| | - Ivan Borbath
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Cliniques Universitaires St. Luc, Université Catholique de Louvain, Belgium
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Wan Y, Hao H, Chen Y, Zhang Y, Yue Q, Li Z. Application of spectral CT combined with perfusion scan in diagnosis of pancreatic neuroendocrine tumors. Insights Imaging 2022; 13:145. [PMID: 36057734 PMCID: PMC9440967 DOI: 10.1186/s13244-022-01282-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 07/20/2022] [Indexed: 11/10/2022] Open
Abstract
Background Pancreatic neuroendocrine tumors (pNETs) are heterogeneous tumors from the pancreatic neuroendocrine system, and early diagnosis is important for tumor prognosis and treatment. In this study, we aimed to explore the diagnostic value of spectral CT combined with perfusion scanning in improving the detection rate of pNETs. Methods From December 2018 to December 2020, 58 patients with clinically suspected pNETs were prospectively enrolled in the study for one-stop spectral CT combined with perfusion scanning, 36 patients were confirmed with pNETs by histopathology. An independent cohort of 30 patients with pNETs who underwent routine pancreatic perfusion scanning in our hospital during the same period were retrospectively collected. The image characters of pNETs versus tumor-free pancreatic parenchymal were examined. Results The detection rate of spectral CT combined with perfusion was 83.1–96.2%. CT values of the pNETs lesions under each single energy in the arterial phase were statistically higher than those of the adjacent normal pancreatic parenchyma. IC, WC and NIC, in the arterial phase of pNETs lesion were all statistically higher than those of the adjacent normal pancreatic parenchyma. The perfusion parameters of pNETs including BF, BV and MSI were significantly higher than those in normal parenchyma. The average effective radiation dose during the perfusion combined energy spectrum enhanced scanning process was 17.51 ± 2.18 mSv. Conclusion The one-stop spectral CT combined with perfusion scan improves the detection of pNETs according to morphological features, perfusion parameters and energy spectrum characters with a relatively small radiation dose.
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Hackeng WM, Assi HA, Westerbeke FHM, Brosens LAA, Heaphy CM. Prognostic and Predictive Biomarkers for Pancreatic Neuroendocrine Tumors. Surg Pathol Clin 2022; 15:541-554. [PMID: 36049835 DOI: 10.1016/j.path.2022.05.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Pancreatic neuroendocrine tumors (PanNETs) represent a clinically challenging disease because these tumors vary in clinical presentation, natural history, and prognosis. Novel prognostic biomarkers are needed to improve patient stratification and treatment options. Several putative prognostic and/or predictive biomarkers (eg, alternative lengthening of telomeres, alpha-thalassemia/mental retardation, X-linked (ATRX)/Death Domain Associated Protein (DAXX) loss) have been independently validated. Additionally, recent transcriptomic and epigenetic studies focusing on endocrine differentiation have identified PanNET subtypes that display similarities to either α-cells or β-cells and differ in clinical outcomes. Thus, future prospective studies that incorporate genomic and epigenetic biomarkers are warranted and have translational potential for individualized therapeutic and surveillance strategies.
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Affiliation(s)
- Wenzel M Hackeng
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
| | - Hussein A Assi
- Department of Medicine, Boston University School of Medicine, 820 Harrison Avenue, FGH 2011, Boston, MA 02118, USA
| | - Florine H M Westerbeke
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands
| | - Christopher M Heaphy
- Department of Medicine, Boston University School of Medicine, 650 Albany Street, Room 444, Boston, MA 02118, USA; Department of Pathology & Laboratory Medicine, Boston University School of Medicine, 650 Albany Street, Room 444, Boston, MA 02118, USA.
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21
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Bell PD, Singhi AD. Integrating Molecular Analysis into the Pathologic Evaluation of Pancreatic Cysts. Surg Pathol Clin 2022; 15:455-468. [PMID: 36049828 DOI: 10.1016/j.path.2022.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
The development of cross-sectional imaging techniques has enhanced the detection of pancreatic cystic lesions (PCLs). PCLs are found in approximately 2% of the general population, often as incidentally detected lesions on computed tomography or MRI during the evaluation of other medical conditions. Broadly, PCLs are classified as mucinous or nonmucinous. Mucinous PCLs include mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. Nonmucinous PCLs include pseudocysts, serous cystadenomas, solid pseudopapillary neoplasms, and cystic pancreatic neuroendocrine tumors, as well as cystic acinar cell carcinoma, cystic degeneration of pancreatic ductal adenocarcinoma, lymphoepithelial cyst, and others.
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Affiliation(s)
- Phoenix D Bell
- Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St. Pittbsurgh, PA 15213, USA.
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, 200 Lothrop St. Pittbsurgh, PA 15213, USA
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22
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La Salvia A, Persano I, Parlagreco E, Audisio A, Cani M, Brizzi MP. Pancreatic adenocarcinoma and pancreatic high-grade neuroendocrine carcinoma: two sides of the moon. Med Oncol 2022; 39:168. [PMID: 35972607 DOI: 10.1007/s12032-022-01764-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 06/09/2022] [Indexed: 06/15/2023]
Abstract
Pancreatic adenocarcinoma is the seventh leading cause of cancer death in the world and the most common type pf pancreatic cancer. Unfortunately, less than 20% of patients are surgically resectable and the great majority of cases are treated with palliative chemotherapy with unsatisfactory results. No targeted agents or personalized approaches have been validated in the last decades. On the other side, neuroendocrine neoplasms of the pancreas are generally considered indolent tumours. However, high-grade neuroendocrine carcinoma is a rare subtype of neuroendocrine neoplasm of the pancreas (accounting up to 10% of the neuroendocrine neoplasms of the pancreas), with particularly aggressive behaviour and poor prognosis. Even in this case, the treatment is represented by palliative chemotherapy with dismal results and no personalized therapies are available, so far. Notably, the quality of life of these patients is disappointingly low and the future perspectives of more personalized diagnostic and therapeutic strategies are scarce. In this review, we discuss relevant and current information on epidemiology, pathology, diagnosis, clinical presentation, treatment and ongoing clinical trials of these two entities, in order to illustrate the two sides of the moon.
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Affiliation(s)
- Anna La Salvia
- Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
| | - Irene Persano
- Department of Oncology, San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Elena Parlagreco
- Department of Oncology, San Luigi Gonzaga Hospital, Orbassano, Italy
| | | | - Massimiliano Cani
- Department of Oncology, San Luigi Gonzaga Hospital, Orbassano, Italy
| | - Maria Pia Brizzi
- Department of Oncology, San Luigi Gonzaga Hospital, Orbassano, Italy
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23
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Rossi G, Petrone MC, Capurso G, Partelli S, Falconi M, Arcidiacono PG. Endoscopic ultrasound radiofrequency ablation of pancreatic insulinoma in elderly patients: Three case reports. World J Clin Cases 2022; 10:6514-6519. [PMID: 35979317 PMCID: PMC9294912 DOI: 10.12998/wjcc.v10.i19.6514] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 10/16/2021] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) has recently been proposed as a local treatment for functional pancreatic neuroendocrine neoplasms in patients unfit for surgery, in order to obtain clinical syndrome regression. Data on the safety and long-term effectiveness of this approach are scarce, and EUS-RFA procedures are not standardized. CASE SUMMARY The present case series reports 3 elderly patients with a pancreatic insulinoma and comorbidities, locally treated by EUS-guided RFA with clinical success in terms of hypoglycemic symptoms. RFA procedures were performed during deep sedation, under EUS control with a 19 G needle, an electrode 5-mm in size at a power of 30 W and multiple RFA applications during the same session in order to treat the whole area of the lesions. Immediate relief of symptoms was evident in 2 patients after the first EUS-RFA, while in the third patient a second endoscopic treatment was needed. All 3 patients are symptom-free without need of medications after 24 mo of follow-up with imaging follow-up showing no disease recurrence. A single adverse event of intraprocedural bleeding occurred, which was successfully treated endoscopically. CONCLUSION EUS-RFA represents an effective and safe alternative to surgery for the treatment of insulinomas in elderly patients at high surgical risk. However, larger multicenter studies with longer follow-up are needed in order to better assess its safety and clinical success.
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Affiliation(s)
- Gemma Rossi
- Division of Pancreato-Biliary Endoscopy and Endosonography, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano 20132, Italy
| | - Maria Chiara Petrone
- Division of Pancreato-Biliary Endoscopy and Endosonography, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano 20132, Italy
| | - Gabriele Capurso
- Division of Pancreato-Biliary Endoscopy and Endosonography, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano 20132, Italy
| | - Stefano Partelli
- Department of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano 20132, Italy
| | - Massimo Falconi
- Department of Pancreatic Surgery, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano 20132, Italy
| | - Paolo Giorgio Arcidiacono
- Division of Pancreato-Biliary Endoscopy and Endosonography, Pancreas Translational and Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milano 20132, Italy
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24
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Lin ZQ, Li X, Yang Y, Wang Y, Zhang XY, Zhang XX, Guo J. Nonfunctional pancreatic neuroendocrine tumours misdiagnosed as autoimmune pancreatitis: A case report and review of literature. World J Clin Cases 2022; 10:4886-4894. [PMID: 35801029 PMCID: PMC9198893 DOI: 10.12998/wjcc.v10.i15.4886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 10/29/2021] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonfunctional pancreatic neuroendocrine tumours are difficult to diagnose in the early stage of disease due to a lack of clinical symptoms, but they can rarely manifest as autoimmune pancreatitis. Autoimmune pancreatitis is an uncommon disease that may cause recurrent acute pancreatitis and is therefore often regarded as a special type of chronic pancreatitis.
CASE SUMMARY We report a case of a 42-year-old female who had nonspecific upper abdominal pain for 4 years and radiological abnormalities of the pancreas that mimicked autoimmune pancreatitis. The symptoms and pancreatic imaging did not improve following 1 year of steroid therapy. Finally, pancreatic biopsy was performed through endoscopic ultrasonography-guided fine-needle aspiration biopsy, and nonfunctional pancreatic neuroendocrine tumours were ultimately diagnosed. Pancreatectomy has resolved her symptoms.
CONCLUSION Therefore, the differentiation of nonfunctional pancreatic neuroendocrine tumours from autoimmune pancreatitis is very important, although it is rare. We propose that endoscopic ultrasonography-guided fine-needle aspiration biopsy should be performed if imaging characteristics are equivocal or the diagnosis is in question.
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Affiliation(s)
- Zi-Qi Lin
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xin Li
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yan Yang
- Laboratory Medicine, West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yi Wang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Ying Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Xin Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia Guo
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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25
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Hue JJ, Sugumar K, Mohamed A, Selfridge JE, Bajor D, Hardacre JM, Ammori JB, Rothermel LD, Winter JM, Ocuin LM. Assessing the Role of Operative Intervention in Elderly Patients With Nonfunctional Pancreatic Neuroendocrine Neoplasms. Pancreas 2022; 51:380-387. [PMID: 35695765 DOI: 10.1097/mpa.0000000000002023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Resection of locoregional pancreatic neuroendocrine neoplasms (PanNENs) is typically recommended, but there is a paucity of data on the management of elderly patients. METHODS The National Cancer Database (2004-2016) was queried for patients 80 years or older with localized PanNENs. Patients were grouped as nonoperative or operative management. Postoperative outcomes and survival were compared. RESULTS In total, 591 patients were included: 202 underwent resection, and 389 did not. Increasing age and pancreatic head tumors were associated with lower likelihood of resection. The overall 90-day mortality rate was 6.4%, which was higher for pancreatoduodenectomy than distal pancreatectomy (13.6% vs 5.1%, respectively). Operatively managed patients had longer median survival (80.8 vs 45.0 months, P < 0.001), and this association was independent of tumor location. On multivariable Cox regression, resection remained associated with longer survival (hazard ratio, 0.69; 95% confidence interval, 0.50-0.95). Among operatively managed patients, age and tumor location were not associated with survival; however, greater comorbidity and high-risk tumor-specific features were associated with worse survival. CONCLUSIONS Resection of nonfunctional PanNENs in elderly patients is associated with improved survival compared with nonoperative management. Resection could be considered in appropriate operative candidates, regardless of tumor location, but the perioperative mortality rate must be considered.
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Affiliation(s)
- Jonathan J Hue
- From the Division of Surgical Oncology, Department of Surgery
| | - Kavin Sugumar
- From the Division of Surgical Oncology, Department of Surgery
| | - Amr Mohamed
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - J Eva Selfridge
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | - David Bajor
- Department of Medicine, Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH
| | | | - John B Ammori
- From the Division of Surgical Oncology, Department of Surgery
| | | | - Jordan M Winter
- From the Division of Surgical Oncology, Department of Surgery
| | - Lee M Ocuin
- From the Division of Surgical Oncology, Department of Surgery
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26
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Hue JJ, Sugumar K, Ammori JB, Rothermel LD, Hardacre JM, Winter JM, Ocuin LM. Facility type and size-stratified analysis of management patterns and outcomes of patients with localized non-functional pancreatic neuroendocrine tumors. HPB (Oxford) 2022; 24:498-506. [PMID: 34419354 DOI: 10.1016/j.hpb.2021.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 04/10/2021] [Accepted: 07/16/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Non-functional neuroendocrine tumors of the pancreas (NF-pNETs) are uncommon. Consensus guidelines have conflicting recommendations. We performed a nationwide analysis of patterns in management and outcomes based on facility type and tumor size. METHODS The National Cancer Database (2004-2016) was queried for patients with localized NF-pNETs (<1 cm, 1-2 cm, >2 cm) stratified by facility type. Management decisions, operative outcomes, and survival were compared. RESULTS A total of 7170 patients were included in the analysis (<1 cm = 916; 1-2 cm = 2180; >2 cm = 4074). Most patients were treated at academic facilities (62.8%). Over 67% of patients with tumors <1 cm underwent resection, independent of facility type (p = 0.443). There was no association between facility type and operative vs non-operative management of patients with NF-pNETs 1-2 cm in size. Patients treated at academic facilities were more likely to undergo resection for tumors >2 cm compared to other facility types. Resection was associated with improved survival among patients with tumors 1-2 cm (HR = 0.43,p < 0.001) and >2 cm (HR = 0.32,p < 0.001), but not <1 cm (HR = 0.64,p = 0.054), as compared to non-operative management. CONCLUSION There is heterogeneity in management of NF-pNETs across facility types. Treatment at academic facilities appears to be associated with higher resection rates for tumors >2 cm. There appears to be an independent association between operative management and improved survival for tumors ≥1 cm in size.
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Affiliation(s)
- Jonathan J Hue
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Kavin Sugumar
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - John B Ammori
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Luke D Rothermel
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jeffrey M Hardacre
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Jordan M Winter
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Lee M Ocuin
- Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
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27
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Cherchir F, Naceur I, Haouari AA, Ben Achour T, Ben Mansour H, Bellil K, Said F, Houman MH. Unilateral pseudouveitis revealing a pancreatic neuroendocrine carcinoma: A case report. Clin Case Rep 2022; 10:e05563. [PMID: 35280094 PMCID: PMC8905139 DOI: 10.1002/ccr3.5563] [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: 01/11/2022] [Revised: 02/17/2022] [Accepted: 02/20/2022] [Indexed: 12/04/2022] Open
Abstract
Neuroendocrine tumors are a heterogeneous group of tumors with a wide range of malignant potential that tend to have a relative prolonged course. These tumors infrequently metastasize to the orbit. To the best of our knowledge, ocular metastases from pancreatic neuroendocrine tumors (PNETs) have never been reported in the literature. We report the case of a 61-year-old man who presented with progressive deterioration of general condition with unilateral recurrent episodes of non-granulomatous panuveitis of the left eye related to a choroidal metastasis. Radiological imaging and histopathological analyses led to the diagnosis of metastatic pancreatic neuroendocrine carcinoma as the primary tumor. Choroidal metastases from neuroendocrine tumors are extremely rare, but compromise patients' well-being because of visual impairment. Uncommonly, these metastases can be the first manifestation of unknown tumors, warranting further investigations to detect the primary cancer.
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Affiliation(s)
- Faten Cherchir
- Department of Internal MedicineLa Rabta University HospitalUniversity of Tunis El ManarTunisTunisia
| | - Ines Naceur
- Department of Internal MedicineLa Rabta University HospitalUniversity of Tunis El ManarTunisTunisia
| | - Ahmed Anas Haouari
- Department of Medical OncologySalah Azaiez InstituteUniversity of Tunis El ManarTunisTunisia
| | - Tayssir Ben Achour
- Department of Internal MedicineLa Rabta University HospitalUniversity of Tunis El ManarTunisTunisia
| | - Hajer Ben Mansour
- Department of Medical OncologySalah Azaiez InstituteUniversity of Tunis El ManarTunisTunisia
| | - Khadija Bellil
- Department of Anatomic PathologyLa Rabta University HospitalUniversity Tunis El ManarTunisTunisia
| | - Fatma Said
- Department of Internal MedicineLa Rabta University HospitalUniversity of Tunis El ManarTunisTunisia
| | - Mohamed Habib Houman
- Department of Internal MedicineLa Rabta University HospitalUniversity of Tunis El ManarTunisTunisia
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Racial disparities in operative management of localized, non-functional pancreatic neuroendocrine tumors in surgically fit patients. HPB (Oxford) 2022; 24:217-225. [PMID: 34247942 DOI: 10.1016/j.hpb.2021.06.418] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/16/2021] [Accepted: 06/11/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Guidelines recommend resection of non-functional neuroendocrine tumors of the pancreas (NF-pNETs) that are ≥2 cm in size. We compared utilization of surgery based on race. METHODS We identified non-Hispanic White and Black patients with localized NF-pNETs ≥2 cm and Charlson-Deyo score 0-1 in the NCDB (2004-2016). We compared utilization of surgery by race, adjusting for clinicodemographic variables. Overall survival was compared based on management. RESULTS A total of 3459 patients were included (White = 3005; Black = 454). Black patients were younger (58vs63 years) and more often treated at academic facilities (65.3%vs60.3%). Overall, Black and White patients underwent surgery at similar rates (77.3%vs79.6%). When stratified by primary site, Black patients with body/tail tumors were less likely to undergo surgery (78.5%vs84.7%). On multivariable analysis, Black race was associated with a lower likelihood of surgery overall (OR 0.74,p = 0.034) and in patients with body/tail tumors (OR 0.56,p = 0.001). Non-operative management was associated with a higher risk of death (HR 3.19,p < 0.001). CONCLUSION In a national cohort of patients with NF-pNETs meeting criteria for resection, Black race is associated with lower frequency of surgery. Operative intervention is associated with prolonged survival. Persistent racial disparities in management of a surgically curable disease should be targeted for improvement.
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29
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Havasi A, Sur D, Cainap SS, Lungulescu CV, Gavrilas LI, Cainap C, Vlad C, Balacescu O. Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers. Int J Mol Sci 2022; 23:1109. [PMID: 35163032 PMCID: PMC8834851 DOI: 10.3390/ijms23031109] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/10/2022] [Accepted: 01/18/2022] [Indexed: 12/17/2022] Open
Abstract
Pancreatic neuroendocrine tumors (PanNETs) are rare tumors; however, their incidence greatly increases with age, and they occur more frequently among the elderly. They represent 5% of all pancreatic tumors, and despite the fact that low-grade tumors often have an indolent evolution, they portend a poor prognosis in an advanced stages and undifferentiated tumors. Additionally, functional pancreatic neuroendocrine tumors greatly impact quality of life due to the various clinical syndromes that result from abnormal hormonal secretion. With limited therapeutic and diagnostic options, patient stratification and selection of optimal therapeutic strategies should be the main focus. Modest improvements in the management of pancreatic neuroendocrine tumors have been achieved in the last years. Therefore, it is imperative to find new biomarkers and therapeutic strategies to improve patient survival and quality of life, limiting the disease burden. MicroRNAs (miRNAs) are small endogenous molecules that modulate the expression of thousands of genes and control numerous critical processes involved in tumor development and progression. New data also suggest the implication of miRNAs in treatment resistance and their potential as prognostic or diagnostic biomarkers and therapeutic targets. In this review, we discusses the current and new challenges in the management of PanNETs, including genetic and epigenetic approaches. Furthermore, we summarize the available data on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discuss their function as future therapeutic targets.
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Affiliation(s)
- Andrei Havasi
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania; (A.H.); (C.C.)
- 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
- MedEuropa Radiotherapy Center, 410191 Oradea, Romania
| | - Daniel Sur
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania; (A.H.); (C.C.)
- 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
| | - Simona Sorana Cainap
- Department of Mother and Child, Pediatric Cardiology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
| | | | - Laura-Ioana Gavrilas
- Department of Bromatology, Hygiene, Nutrition, University of Medicine and Pharmacy “Iuliu Hatieganu”, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;
| | - Calin Cainap
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 400015 Cluj-Napoca, Romania; (A.H.); (C.C.)
- 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
| | - Catalin Vlad
- Department of Surgery, The Oncology Institute “Prof. Dr. Ion Chiricuta”, 34–36, Republicii Street, 400015 Cluj-Napoca, Romania;
- Department of Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 8, Victor Babes Street, 400012 Cluj-Napoca, Romania
| | - Ovidiu Balacescu
- 11th Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400015 Cluj-Napoca, Romania;
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuta’’, 400015 Cluj-Napoca, Romania
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30
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Brugel M, Walter T, Goichot B, Smith D, Lepage C, Do Cao C, Hautefeuille V, Rebours V, Cadiot G, de Mestier L. Efficacy of treatments for VIPoma: A GTE multicentric series. Pancreatology 2021; 21:1531-1539. [PMID: 34404601 DOI: 10.1016/j.pan.2021.08.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/28/2021] [Accepted: 08/04/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Vasoactive intestinal peptide-secreting tumor (VIPoma) is a very rare, life-threatening, functioning pancreatic neuroendocrine tumor (pNET). The efficacy of antitumor therapies against functioning symptoms and tumor burden have been poorly described in VIPoma. OBJECTIVE Describe the impact of treatments on the secretory syndrome, tumor burden and survival in patients with VIPoma. METHODS We retrospectively reviewed the records of patients with VIPoma treated in seven French expert centers between 1990 and 2016. Diagnostic of VIPoma was reassessed using strict criteria. We evaluated the antisecretory efficacy (>50 % decrease of daily bowel movements), and antitumor efficacy (RECIST 1.1) of all treatments received. RESULTS Twenty-two patients were included. pNETs were mostly metastatic (77 %) and classified as grade 2 (83 %). Median follow-up was 78.2 months. Surgical excision of nonmetastatic VIPoma effectively controlled the secretory syndrome. Although 4/5 patients had metastatic recurrences, all patients were alive after median post-operative follow-up of 171 months. Among the 87 treatments received for metastatic VIPoma, curative-intent surgery (n = 14), somatostatin analogs alone (n = 11), chemotherapy (n = 23), transarterial liver embolization (TALE) (n = 14), everolimus (n = 10) and sunitinib (n = 7) achieved, respectively, 100 %, 67 %, 83 %, 50 %, 20 % and 100 % antisecretory efficacy. The 5-year OS rate was 63.6 %, with pejorative impact of higher Ki-67 index (P = 0.045) and higher plasma VIP concentration (P = 0.025). CONCLUSIONS Surgical resection of localized VIPoma is effective but rarely curative. For metastatic VIPoma, curative-intent surgery, chemotherapy and sunitinib are the therapeutic options that best combined antitumor and antisecretory efficacies.
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Affiliation(s)
- Mathias Brugel
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré Hospital and Reims-Champagne-Ardenne University, Reims, France.
| | - Thomas Walter
- Department of Digestive Oncology, ENETS Centre of Excellence, Hospices Civils de Lyon, Lyon, France
| | - Bernard Goichot
- Department of Internal Medicine, Endocrinology & Nutrition, Hôpital Hautepierre, Strasbourg University Hospital, France
| | - Denis Smith
- Department of Hepato-Gastroenterology and Digestive Oncology, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Côme Lepage
- Department of Hepato-Gastroenterology and Digestive Oncology, Dijon University Hospital, Dijon, France
| | - Christine Do Cao
- Department of Endocrinology, Hôpital Claude-Huriez, Lille University Hospital, Lille, France
| | - Vincent Hautefeuille
- Department of Hepato-Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | - Vinciane Rebours
- Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Hôpital Beaujon and Université de Paris Nord, Clichy, France
| | - Guillaume Cadiot
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré Hospital and Reims-Champagne-Ardenne University, Reims, France
| | - Louis de Mestier
- Department of Gastroenterology-Pancreatology, ENETS Centre of Excellence, Hôpital Beaujon and Université de Paris Nord, Clichy, France
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Segaran N, Devine C, Wang M, Ganeshan D. Current update on imaging for pancreatic neuroendocrine neoplasms. World J Clin Oncol 2021; 12:897-911. [PMID: 34733612 PMCID: PMC8546658 DOI: 10.5306/wjco.v12.i10.897] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/21/2021] [Accepted: 08/27/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNEN) are a heterogeneous group of tumors with differing pathological, genetic, and clinical features. Based on clinical findings, they may be categorized into functioning and nonfunctioning tumors. Adoption of the 2017 World Health Organization classification system, particularly its differentiation between grade 3, well-differentiated pancreatic neuroendocrine tumors (panNET) and grade 3, poorly-differentiated pancreatic neuroendocrine carcinomas (panNEC) has emphasized the role imaging plays in characterizing these lesions. Endoscopic ultrasound can help obtain biopsy specimen and assess tumor margins and local spread. Enhancement patterns on computed tomography (CT) and magnetic resonance imaging (MRI) may be used to classify panNEN. Contrast enhanced MRI and diffusion-weighted imaging have been reported to be useful for characterization of panNEN and quantifying metastatic burden. Current and emerging radiotracers have broadened the utility of functional imaging in evaluating panNEN. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET)/CT and somatostatin receptor imaging such as Gallium-68 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate PET/CT may be useful for improved identification of panNEN in comparison to anatomic modalities. These new techniques can also play a direct role in optimizing the selection of treatment for individuals and predicting tumor response based on somatostatin receptor expression. In addition, emerging methods of radiomics such as texture analysis may be a potential tool for staging and outcome prediction in panNEN, however further investigation is required before clinical implementation.
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Affiliation(s)
- Nicole Segaran
- Department of Radiology, Mayo Clinic Arizona, Phoenix, AZ 85259, United States
| | - Catherine Devine
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Mindy Wang
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Dhakshinamoorthy Ganeshan
- Department of Diagnostic Radiology, Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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Long-term outcome after EUS-guided radiofrequency ablation: Prospective results in pancreatic neuroendocrine tumors and pancreatic cystic neoplasms. Endosc Int Open 2021; 9:E1178-E1185. [PMID: 34447860 PMCID: PMC8383082 DOI: 10.1055/a-1479-2199] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 10/29/2020] [Indexed: 12/14/2022] Open
Abstract
Background and study aims Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for pancreatic neuroendocrine tumors (NETs) and intraductal pancreatic mucinous neoplasia (IPMN) with worrisome features or high-risk stigmata (WF/HRS) has been evaluated in few series with short-term outcomes. This study's primary endpoint was to assess the long-term efficacy of EUS-RFA in patients with NETs or pancreatic cystic neoplasms (PCNs) over at least 3 years. Patients and methods Twelve patients had 14 NETs with a mean 13.4-mm size (10-20) and 17 patients had a cystic tumor (16 IPMN, 1 MCA) with a 29.1-mm mean size (9-60 were included. They were treated with EUS-guided RFA, evaluated prospectively at 1 year, and followed annually for at least 3 years. Results The mean duration of follow-up was 42.9 months (36-53). Four patients died during follow-up (17-42 months) from unrelated diseases. At 1-year follow-up, and 85.7 % complete disappearance was seen in 12 patients with 14 NETs. At the end of follow-up (45.6 months), complete disappearance of tumors was seen in 85.7 % of cases. One case of late liver metastasis occurred in a patient with initial failure of EUS-RFA. At 1-year follow-up, a significant response was seen in 70.5 % of 15 patients with PCNs. At the end of the follow-up, there was a significant response in 66.6 % with no mural nodules. Two cases of distant pancreatic adenocarcinoma unrelated to IPMN occurred. Conclusions EUS-RFA results for pancreatic NETs or PCNs appear to be stable during 42 months of follow-up.
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Ishikawa R, Kamata K, Hara A, Tanaka H, Okamoto A, Yamazaki T, Nakai A, Omoto S, Minaga K, Yamao K, Takenaka M, Minami Y, Watanabe T, Chiba Y, Chikugo T, Matsumoto I, Takeyama Y, Matsukubo Y, Hyodo T, Kudo M. Utility of contrast-enhanced harmonic endoscopic ultrasonography for predicting the prognosis of pancreatic neuroendocrine neoplasms. Dig Endosc 2021; 33:829-839. [PMID: 33020955 DOI: 10.1111/den.13862] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 09/28/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Pancreatic neuroendocrine neoplasms (PanNENs), including Grade 1 (G1) or G2 tumors, can have a poor prognosis. This study investigated the value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for predicting the prognosis of PanNENs. METHODS This single-center, retrospective study included 47 consecutive patients who underwent CH-EUS and were diagnosed with PanNEN by surgical resection or EUS-guided fine needle aspiration between December 2011 and February 2016. Patients were divided into aggressive and non-aggressive groups according to the degree of clinical malignancy. CH-EUS was assessed regarding its capacity for diagnosing aggressive PanNEN, the correspondence between contrast patterns and pathological features, and its ability to predict the prognosis of PanNEN. RESULTS There were 19 cases of aggressive PanNEN and 28 cases of non-aggressive PanNEN. The aggressive group included three G1, four G2, three G3 tumors, three mixed neuroendocrine non-neuroendocrine neoplasms, and six neuroendocrine carcinomas. CH-EUS was superior to contrast-enhanced computed tomography for the diagnosis of aggressive PanNEN (P < 0.001): hypo-enhancement on CH-EUS was an indicator of aggressive PanNEN, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94.7%, 100%, 100%, 96.6%, and 97.9%, respectively. Among G1/G2 PanNENs, cases with hypo-enhancement on CH-EUS had a poorer prognosis than those with hyper/iso-enhancement (P = 0.0009). Assessment of 36 resected specimens showed that hypo-enhancement on CH-EUS was associated with smaller and fewer vessels and greater degree of fibrosis. CONCLUSION Contrast-enhanced harmonic endoscopic ultrasonography may be useful for predicting the prognosis of PanNENs.
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Affiliation(s)
- Rei Ishikawa
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Akane Hara
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Hidekazu Tanaka
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Ayana Okamoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Tomohiro Yamazaki
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Atsushi Nakai
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Shunsuke Omoto
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Kosuke Minaga
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Kentaro Yamao
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Mamoru Takenaka
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Tomohiro Watanabe
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Yasutaka Chiba
- Clinical Research Center, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Takaaki Chikugo
- Department of Diagnostic Pathology, Kindai University Hospital, Osaka, Japan
| | - Ippei Matsumoto
- Departments of, Department of, Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Yoshifumfi Takeyama
- Departments of, Department of, Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Yuko Matsukubo
- Department of, Radiology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Tomoko Hyodo
- Department of, Radiology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
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Abstract
OBJECTIVE. The purpose of this article is to review the clinical manifestations, endocrine tumors types, and multimodality diagnostic tools available to physicians involved in the management of patients with multiple endocrine neoplasia (MEN) syndrome, in addition to discussing relevant imaging findings and appropriate imaging follow-up. CONCLUSION. Thorough knowledge of the spectrum of tumors associated with MEN gene mutations aids in the screening, diagnostic workup, and posttreatment monitoring of patients with MEN-related gene mutations.
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Garnier H, Loo C, Czauderna P, Vasudevan SA. Pediatric Gastrointestinal Stromal Tumors and Neuroendocrine Tumors: Advances in Surgical Management. Surg Oncol Clin N Am 2021; 30:219-233. [PMID: 33706897 DOI: 10.1016/j.soc.2020.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastrointestinal stromal tumors and neuroendocrine tumors in adult and pediatric populations differ immensely. Despite these established differences, the extreme rarity of gastrointestinal stromal tumors and neuroendocrine tumors in the pediatric population has resulted in the lack of consensus management guidelines, making optimal surgical approaches unclear. Comprehensive management principles to guide surgical approaches in adult literature are extensive. However, these are still lacking for pediatric patients. International cooperation to develop standardized pediatric-specific guidelines is urgently warranted in the future. This article highlights the vast differences between adult and pediatric parameters and provides recommendations on optimal and novel surgical approaches in children.
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Affiliation(s)
- Hanna Garnier
- Department of Surgery and Urology for Children and Adolescents, Medical University of Gdansk, Marii Skłodowskiej-Curie 3a, Gdańsk 80-210, Poland
| | - Caitlyn Loo
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, 7200 Cambridge Street, 7th Floor, Houston, TX 77030, USA; School of Medicine, Royal College of Surgeons in Ireland, 123 St Stephens Green, Saint Peter's, Dublin D02 YN77, Ireland
| | - Piotr Czauderna
- Department of Surgery and Urology for Children and Adolescents, Medical University of Gdansk, Marii Skłodowskiej-Curie 3a, Gdańsk 80-210, Poland
| | - Sanjeev A Vasudevan
- Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, 7200 Cambridge Street, 7th Floor, Houston, TX 77030, USA.
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Application of low dose pancreas perfusion CT combined with enhancement scanning in diagnosis of pancreatic neuroendocrine tumors. Pancreatology 2021; 21:240-245. [PMID: 33191144 DOI: 10.1016/j.pan.2020.10.046] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 10/02/2020] [Accepted: 10/24/2020] [Indexed: 12/11/2022]
Abstract
PURPOSE To explore the diagnostic value of pancreatic perfusion CT combined with contrast-enhanced CT in one-time scanning (PCECT) in pancreatic neuroendocrine tumors (PNETs) and to evaluate the difference of perfusion parameters between different grades of PNETs. MATERIALS AND METHODS From October 2016 to December 2018, forty consecutive patients with histopathological-proven PNETs were identified retrospectively that received PCECT for the preoperative PNETs evaluation. Two board certified radiologists who were blinded to the clinical data evaluated the images independently. The image characters of PNETs vs. tumor-free pancreatic parenchymal and different grades of PNETs were analyzed. RESULTS One-time PCECT scanning had a detection rate of 89.1% for PNETs, which was higher than the detection accuracy of the perfusion CT only (83.6%). The perfusion parameters of PNETs including blood volume (BV), blood flow (BF), mean slope of increase (MSI), and capillary surface permeability (PS) were significantly increased than those of tumor-free pancreatic parenchyma (p < 0.05, respectively). For differential comparison between grade I (G1) and grade II (G2) tumors, the parameters of BF and impulse residue function (IRF) of tumor tissue were significantly higher in the G2 tumors (p < 0.05, for both). In this study, the total radiation dose of the whole PCECT scan was 16.241 ± 2.289 mSv. CONCLUSION The one-time PCECT scan may improve the detection of PNETs according to morphological features and perfusion parameters with a relative small radiation dose. The perfusion parameters of BF and IRF may be used to help distinguish G1 and G2 tumors in the preoperative evaluation.
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Khan T, Paul BK, Hasan MT, Islam MR, Arefin M, Ahmed K, Islam MK, Moni MA. Significant pathway and biomarker identification of pancreatic cancer associated lung cancer. INFORMATICS IN MEDICINE UNLOCKED 2021. [DOI: 10.1016/j.imu.2021.100637] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
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Bispo M, Caldeira A, Leite S, Marques S, Moreira T, Moutinho-Ribeiro P, Nunes N. Endoscopic Ultrasound-Guided Ablation of Focal Pancreatic Lesions: The GRUPUGE Perspective. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2020; 27:410-416. [PMID: 33251290 DOI: 10.1159/000507895] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2020] [Accepted: 04/13/2020] [Indexed: 12/26/2022]
Abstract
Focal pancreatic lesions include a heterogeneous group of solid and cystic lesions, with different natures and variable clinical, imagiological, and pathological characteristics. Several endoscopic ultrasound (EUS)-guided ablative techniques have been tested during the last decade for the treatment of these pancreatic lesions, mostly consisting of the injection of ablative agents and, more recently, radiofrequency ablation. The most encouraging EUS-guided ablation outcomes are being reached in the treatment of some pancreatic cystic neoplasms and small (≤2 cm) pancreatic neuroendocrine tumours (pNETs). Data supporting a potential role of ablative therapies in the treatment of pancreatic ductal adenocarcinoma is still lacking. In this article, GRUPUGE presents an updated perspective of the potential role of EUS-guided ablation for the treatment of pancreatic cystic neoplasms and pNETs, addressing the selection criteria and technical issues of different techniques and analysing recent data on their safety and efficacy.
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Affiliation(s)
- Miguel Bispo
- Department of Gastroenterology and Digestive Endoscopy, Champalimaud Foundation, Lisbon, Portugal
| | - Ana Caldeira
- Department of Gastroenterology, Hospital Amato Lusitano, Castelo Branco, Portugal
| | - Sílvia Leite
- Department of Gastroenterology, Hospital da Senhora da Oliveira, Guimarães, Portugal
| | - Susana Marques
- Department of Gastroenterology and Digestive Endoscopy, Champalimaud Foundation, Lisbon, Portugal
| | - Teresa Moreira
- Department of Gastroenterology, Centro Hospitalar Universitário do Porto - Hospital de Santo António, Porto, Portugal
| | - Pedro Moutinho-Ribeiro
- Department of Gastroenterology, Centro Hospitalar e Universitário São João, Porto, Portugal
| | - Nuno Nunes
- Department of Gastroenterology, Hospital do Divino Espírito Santo, Ponta Delgada, São Miguel, Portugal
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Imperatore N, de Nucci G, Mandelli ED, de Leone A, Zito FP, Lombardi G, Manes G. Endoscopic ultrasound-guided radiofrequency ablation of pancreatic neuroendocrine tumors: a systematic review of the literature. Endosc Int Open 2020; 8:E1759-E1764. [PMID: 33269308 PMCID: PMC7671767 DOI: 10.1055/a-1261-9605] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 08/18/2020] [Indexed: 12/17/2022] Open
Abstract
Background and study aims Surgery is the mainstay therapy for pancreatic neuroendocrine tumors (P-NETs), but it is associated with significant adverse events (AEs). In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been described for treating P-NETs. We performed a systematic literature review aimed at exploring the feasibility, effectiveness, and safety of EUS-RFA in treatment of P-NETs. Methods The literature review was performed in PubMed/MEDLINE, EMBASE, and SCOPUS to identify all case reports of EUS-RFA for treatment of P-NETs. Results Sixyt-one patients (males 49.2 %, mean age 64.5 years) and 73 tumors (mean size 16 mm, insulinomas 30.1 %) treated with EUS-RFA were included from 12 studies. The overall effectiveness of EUS-RFA was 96 % (75 % - 100 %) without differences between functional vs. non-functional P-NETs ( P = 0.3) and without relevant issues about safety (mild AEs 13.7 %). While tumor location was not predictive for incomplete/non-response to EUS-RFA, greater tumor dimensions predicted treatment failure (21.8 ± 4.71 mm in the non-response group vs 15.07 ± 7.34 mm in the response group, P = 0.048). At ROC analysis, a P-NET size cut-off value ≤18 mm predicted response to treatment, with a sensitivity of 80 % (95 % CI 28.4 % - 99.5 %), a specificity of 78.6 % (95 % CI 63.2 % - 89.7 %), a positive predictive value of 97.1 % (95 % CI 84.7 % - 99.9 %) and a negative predictive value of 30.8 % (95 % CI 9.1 % - 61.4 %), with an area under the curve of 0.81 (95 % CI 0.67 - 0.95). Conclusions EUS-RFA is safe and effective for treating P-NETs. It may be reasonable to consider EUS-RFA for small P-NETs, irrespective of the functional status.
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Affiliation(s)
- Nicola Imperatore
- Gastroenterology and Endoscopy Unit, AORN A Cardarelli, Naples, Italy
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine Federico II of Naples, Naples, Italy
| | - Germana de Nucci
- Gastroenterology and Endoscopy Unit, ASST Rhodense, Garbagnate Milanese, Milan, Italy
| | | | - Annalisa de Leone
- Gastroenterology and Endoscopy Unit, AORN A Cardarelli, Naples, Italy
| | | | - Giovanni Lombardi
- Gastroenterology and Endoscopy Unit, AORN A Cardarelli, Naples, Italy
| | - Gianpiero Manes
- Gastroenterology and Endoscopy Unit, ASST Rhodense, Garbagnate Milanese, Milan, Italy
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de Nucci G, Imperatore N, Mandelli ED, di Nuovo F, d’Urbano C, Manes G. Endoscopic ultrasound-guided radiofrequency ablation of pancreatic neuroendocrine tumors: a case series. Endosc Int Open 2020; 8:E1754-E1758. [PMID: 33269307 PMCID: PMC7671764 DOI: 10.1055/a-1261-9359] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 08/18/2020] [Indexed: 12/30/2022] Open
Abstract
Background and study aims Surgery is the considered the therapeutic cornerstone for pancreatic neuroendocrine tumors (P-NETs), although burdened by high risk of significant adverse events. Recently, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been described for P-NETs. We aimed to evaluate the effectiveness and safety of EUS-RFA for treatment of P-NETs. Patients and methods We prospectively included all consecutive patients with P-NET ≤ 20 mm who were treated with EUS-RFA and were followed-up for at least 12 months. Results Ten patients (5 males, mean age 78.6 years, mean body mass index 28.2) with 11 P-NETs (mean size 14.5 mm; range 9 - 20 mm) localized in the pancreatic head (3 lesions), pancreatic body (5 lesions), and tail (3 lesions) underwent complete EUS ablation with one session of RFA. Complete ablation of P-NET was reached using a single-session RFA with a mean of 2.3 treatment applications per session. At both 6 - and 12-months computed tomography scans, all the patients had complete disappearance of lesions with radiological normalization. Regarding safety, only two cases of mild abdominal pain were recorded in two subjects with pancreatic head lesion, which were effectively treated with analgesics. The mean duration of hospital stay was 4 days (range 3 - 7 days). Conclusions EUS-RFA is effective and safe in treating P-NETs. It may be considered an effective therapeutic option in the treatment of small P-NETs independently from their functional status.
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Affiliation(s)
- Germana de Nucci
- Gastroenterology and Endoscopy Unit, ASST Rhodense, Garbagnate Milanese, Milan, Italy
| | - Nicola Imperatore
- Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine Federico II of Naples, Naples, Italy,Gastroenterology and Endoscopy Unit, AORN A Cardarelli, Naples, Italy
| | | | - Franca di Nuovo
- Pathology Unit, ASST Rhodense, Garbagnate Milanese, Milan, Italy
| | | | - Gianpiero Manes
- Gastroenterology and Endoscopy Unit, ASST Rhodense, Garbagnate Milanese, Milan, Italy
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Bhat AS, Farrugia A, Marangoni G, Ahmad J. Multivisceral robotic resection: a glimpse into the future of minimally invasive abdominal surgery. BMJ Case Rep 2020; 13:e234887. [PMID: 32843403 PMCID: PMC7449279 DOI: 10.1136/bcr-2020-234887] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2020] [Indexed: 01/30/2023] Open
Abstract
A 62-year-old man was referred to the Hepato-Pancreato-Biliary (HPB) surgeons with left upper quadrant discomfort. The initial investigations and CT scans revealed a tumour in the pancreatic tail with liver metastases, confirmed on MRI. It was initially thought to be an adenocarcinoma; however, further investigations found that it was a grade 1 neuroendocrine tumour with Ki 67 at 1% and it was agreed that he would undergo a total robotic surgery involving resection of the locally advanced tumour of the tail of pancreas, with the involvement of the stomach, and splenic flexure of the colon with liver metastases. The resulting procedure was a total robotic distal pancreatectomy, splenectomy, sleeve resection of stomach, cholecystectomy, atypical resection of two liver lesions and microwave ablation of multiple liver lesions. Four days post-operatively, he was discharged from hospital and commenced adjuvant chemotherapy. He currently enjoys a good quality of life.
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Affiliation(s)
| | - Alexia Farrugia
- Warwick Medical School, University of Warwick, Coventry, West Midlands, UK
- General and Hepatobiliary Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Gabriele Marangoni
- Warwick Medical School, University of Warwick, Coventry, West Midlands, UK
- General and Hepatobiliary Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
| | - Jawad Ahmad
- Warwick Medical School, University of Warwick, Coventry, West Midlands, UK
- General and Hepatobiliary Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
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Mpilla GB, Philip PA, El-Rayes B, Azmi AS. Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations. World J Gastroenterol 2020; 26:4036-4054. [PMID: 32821069 PMCID: PMC7403797 DOI: 10.3748/wjg.v26.i28.4036] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 06/10/2020] [Accepted: 07/16/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreatic neuroendocrine tumors (PNETs) are known to be the second most common epithelial malignancy of the pancreas. PNETs can be listed among the slowest growing as well as the fastest growing human cancers. The prevalence of PNETs is deceptively low; however, its incidence has significantly increased over the past decades. According to the American Cancer Society's estimate, about 4032 (> 7% of all pancreatic malignancies) individuals will be diagnosed with PNETs in 2020. PNETs often cause severe morbidity due to excessive secretion of hormones (such as serotonin) and/or overall tumor mass. Patients can live for many years (except for those patients with poorly differentiated G3 neuroendocrine tumors); thus, the prevalence of the tumors that is the number of patients actually dealing with the disease at any given time is fairly high because the survival is much longer than pancreatic ductal adenocarcinoma. Due to significant heterogeneity, the management of PNETs is very complex and remains an unmet clinical challenge. In terms of research studies, modest improvements have been made over the past decades in the identification of potential oncogenic drivers in order to enhance the quality of life and increase survival for this growing population of patients. Unfortunately, the majority of systematic therapies approved for the management of advanced stage PNETs lack objective response or at most result in modest benefits in survival. In this review, we aim to discuss the broad challenges associated with the management and the study of PNETs.
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Affiliation(s)
- Gabriel Benyomo Mpilla
- Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, United States
| | - Philip Agop Philip
- Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, United States
| | - Bassel El-Rayes
- Department of Hematology Oncology, Emory Winship Institute, Atlanta, GA 30322, United States
| | - Asfar Sohail Azmi
- Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, United States
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Malignant Insulinoma with Multiple Liver Metastases and Hypercalcitoninemia in a Patient with Type 2 Diabetes Mellitus Presenting as Recurrent Episodes of Diaphoresis due to Severe Hypoglycemia. Case Rep Endocrinol 2020; 2020:4239679. [PMID: 32082648 PMCID: PMC7019204 DOI: 10.1155/2020/4239679] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 12/18/2019] [Accepted: 01/04/2020] [Indexed: 11/17/2022] Open
Abstract
Insulinoma is an insulin-producing pancreatic neuroendocrine tumor that can be malignant in about 10% of cases. Locoregional invasion, lymph node metastases, or remote metastases are the main criteria of malignant insulinoma. Its incidence in patients with pre-existing diabetes mellitus (DM) is exceptionally rare. In this report, we describe a 66-year-old man with long-standing type 2 DM who presented with recurrent episodes of diaphoresis due to severe hypoglycemia despite the withdrawal of insulin therapy, hypercalcitoninemia, and biochemical and radiological findings suggestive of metastatic malignant insulinoma. Unfortunately, after few days of diazoxide treatment, edema, hypotension, oliguria, and water retention were observed, patient's clinical status deteriorated rapidly, and he died in our department from acute renal failure.
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Suvvari T, Nudurupati R, Kumar Akunuri R, Simhachalam Kutikuppala L. A rare case of pancreatic neuroendocrine tumor. APOLLO MEDICINE 2020. [DOI: 10.4103/am.am_98_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Fang JM, Shi J. A Clinicopathologic and Molecular Update of Pancreatic Neuroendocrine Neoplasms With a Focus on the New World Health Organization Classification. Arch Pathol Lab Med 2019; 143:1317-1326. [PMID: 31509453 PMCID: PMC7141760 DOI: 10.5858/arpa.2019-0338-ra] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
CONTEXT.— According to the 2017 World Health Organization classification, pancreatic neuroendocrine neoplasms (PanNENs) include a new category of pancreatic neuroendocrine tumor, grade 3, which is often difficult to differentiate from pancreatic neuroendocrine carcinoma. However, pancreatic neuroendocrine tumor grade 3 and pancreatic neuroendocrine carcinoma are distinct entities with very different clinical presentation, prognosis, and therapeutic strategies. Recent discoveries on the molecular characteristics of pancreatic neuroendocrine tumors also play an essential role in the pathologic differential diagnosis of PanNENs. In addition, the histopathologic varieties of PanNENs bring in many differential diagnoses with other pancreatic neoplasms, especially acinar cell carcinoma, solid pseudopapillary neoplasm, and ductal adenocarcinoma. OBJECTIVE.— To provide a brief update of the World Health Organization classification; the clinical, histopathologic, immunohistochemical, and molecular characteristics; and the differential diagnoses and biological behavior of PanNENs. DATA SOURCES.— Analysis of the pertinent literature (PubMed) and authors' clinical practice experience based on institutional and consultation materials. CONCLUSIONS.— The evolving clinical, histopathologic, immunohistochemical, and molecular features of PanNENs are reviewed. Important differential diagnoses with other neoplasms of the pancreas are discussed.
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Affiliation(s)
- Jiayun M Fang
- From the Department of Pathology, University of Michigan, Ann Arbor
| | - Jiaqi Shi
- From the Department of Pathology, University of Michigan, Ann Arbor
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Farooqui ZA, Chauhan A. Neuroendocrine Tumors in Pediatrics. Glob Pediatr Health 2019; 6:2333794X19862712. [PMID: 31384627 PMCID: PMC6647200 DOI: 10.1177/2333794x19862712] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 05/14/2019] [Accepted: 05/15/2019] [Indexed: 12/23/2022] Open
Abstract
Neuroendocrine cells are dispersed diffusely throughout many organ systems in the body and hence neuroendocrine tumors (NETs) can arise from almost anywhere in the body. NETs are considered rare tumors, and the current incidence is reported to be about 6 cases in 100 000 in adults and about 2.8 cases per million in the pediatric age group. Despite the indolent nature of these tumors, they have the potential for metastasis and significant morbidity. NETs can be asymptomatic at the time of diagnosis or can present with flushing, diarrhea, wheezing, weight loss, and fatigue among other symptoms. Due to the ambiguity of presenting symptoms, it is not uncommon for NETs to be diagnosed late in the disease course. Despite low incidence, the prevalence of the disease is high since patients live for many years and sometimes decades. Early detection of well-differentiated NETs has excellent outcomes with the majority of early-stage diseases being cured with surgical resection alone. There have been recent advancements in the management of metastatic progressive NETs with approval of peptide receptor radionuclide therapy, telotristat, and everolimus. Awareness of these rare tumors and its management is crucial for optimal management. This article will focus on pediatric NETs and current advances in its management.
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Affiliation(s)
| | - Aman Chauhan
- Markey Cancer Center, Lexington, KY, USA
- University of Kentucky, Lexington, KY, USA
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Bosco D, Perrotti S, Spatola C, Vecchio GM, Latino R, Di Cataldo A. Rare breast and subcutaneous metastases from pancreatic neuroendocrine tumor: a case report. World J Surg Oncol 2019; 17:121. [PMID: 31296241 PMCID: PMC6624935 DOI: 10.1186/s12957-019-1662-0] [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] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 07/01/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Neuroendocrine tumors are a group of rare neoplasms, and the pancreatic neuroendocrine tumors (PNETs) represent only 1-2% of all pancreatic malignant tumors. The most common sites of these tumors include the gastrointestinal tract, lung, adrenal gland, and thyroid gland. Moreover, the most common sites of PNET metastases are the lymph nodes, liver, spleen, and bone. A 40-year-old woman with pT3N1 PNET underwent surgical excision of the lesion (12 cm, at the level of the pancreatic body and tail). Postsurgical treatment included chemotherapy and radiation, both of which the patient showed a good tolerance for. After a 12-month disease-free interval, however, the patient reported the development of a lesion in her left breast and a small lesion in the left posterior region of her neck. The lesions were surgically excised, and the histological findings characterized both as pancreatic neuroendocrine metastatic poorly differentiated neoplasms (G3). A re-staging CT scan showed multiple metastases in the left axillary, clavicular, and latero-cervical lymph nodes, as well as diffuse osteolytic-osteoblastic bone metastases, almost mimicking the behavior of a primitive breast tumor. CONCLUSION This case of breast and subcutaneous metastases from PNET should prompt awareness of potential metastatic lesions in unusual locations.
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Affiliation(s)
- Dorotea Bosco
- Department of General and Oncological Surgery, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Salvatore Perrotti
- Department of General and Oncological Surgery, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.
| | - Corrado Spatola
- Department of Oncology and Radiotherapy, University of Catania, Catania, Italy
| | | | - Rosalia Latino
- Department of General and Oncological Surgery, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Antonio Di Cataldo
- Department of General and Oncological Surgery, University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
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Barthet M. Endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine tumor. ANNALES D'ENDOCRINOLOGIE 2019; 80:182-184. [PMID: 31053252 DOI: 10.1016/j.ando.2019.04.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Marc Barthet
- Service de gastro-entérologie, hôpital Nord, chemin des Bourrely, 13915 Marseille cedex 20, France.
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Guilmette J, Nosé V. Paraneoplastic syndromes and other systemic disorders associated with neuroendocrine neoplasms. Semin Diagn Pathol 2019; 36:229-239. [PMID: 30910348 DOI: 10.1053/j.semdp.2019.03.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Neuroendocrine paraneoplastic syndromes (PNS) consist of metabolic disorders that accompany benign and malignant neoplasms but remain unrelated to mass effects or invasion by the primary tumor or its metastases. The underlying pathogenesis responsible for PNS usual clinical presentation relies on aberrant production of protein hormones, proteins and other substances by the tumor. Prompt recognition of characteristic signs and symptoms combined with serological identification of key substances may result in early diagnosis of PNS and its underlying malignancy. For these reasons, healthcare professionals should familiarize themselves with tumor-induced hypercalcemia, syndrome of inappropriate antidiuretic hormone, carcinoid syndrome, virilisation syndrome, gynecomastia, acromegaly, Cushing syndrome, osteogenic osteomalacia, tumor-induced hypoglycemia, necrolytic migratory erythema, and watery diarrhea, hypokalemia and achlorydria syndrome. Medical awareness for PNS can improve patient outcomes through earlier administration of cancer therapy and treatment, better symptomatic relief and prolong overall survival.
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Affiliation(s)
- Julie Guilmette
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114-2696, United States; Department of Pathology, Charles-Lemoyne Hospital, Greenfield Park, Quebec, Canada
| | - Vânia Nosé
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114-2696, United States.
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Guo CG, Ren S, Chen X, Wang QD, Xiao WB, Zhang JF, Duan SF, Wang ZQ. Pancreatic neuroendocrine tumor: prediction of the tumor grade using magnetic resonance imaging findings and texture analysis with 3-T magnetic resonance. Cancer Manag Res 2019; 11:1933-1944. [PMID: 30881119 PMCID: PMC6407516 DOI: 10.2147/cmar.s195376] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
PURPOSE The purpose of this study was to evaluate the performance of magnetic resonance imaging (MRI) findings and texture parameters for prediction of the histopathologic grade of pancreatic neuroendocrine tumors (PNETs) with 3-T magnetic resonance. PATIENTS AND METHODS PNETs are classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity. A total of 77 patients with pathologically confirmed PNETs met the inclusion criteria. Texture analysis (TA) was applied to T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) maps. Patient demographics, MRI findings, and texture parameters were compared among three different histopathologic subtypes by using Fisher's exact tests or Kruskal-Wallis test. Then, logistic regression analysis was adopted to predict tumor grades. ROC curves and AUCs were calculated to assess the diagnostic performance of MRI findings and texture parameters in prediction of tumor grades. RESULTS There were 31 G1, 29 G2, and 17 G3 patients. Compared with G1, G2/G3 tumors showed higher frequencies of an ill-defined margin, a predominantly solid tumor type, local invasion or metastases, hypo-enhancement at the arterial phase, and restriction diffusion. Four T2-based (inverse difference moment, energy, correlation, and differenceEntropy) and five DWI-based (correlation, contrast, inverse difference moment, maxintensity, and entropy) TA parameters exhibited statistical significance among PNETs (P<0.001). The AUCs of six predicting models on T2WI and DWI ranged from 0.703-0.989. CONCLUSION Our data indicate that MRI findings, including tumor margin, texture, local invasion or metastases, tumor enhancement, and diffusion restriction, as well as texture parameters can aid the prediction of PNETs grading.
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Affiliation(s)
- Chuan-Gen Guo
- Department of Radiology, The First Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310003, China
| | - Shuai Ren
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China,
| | - Xiao Chen
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China,
| | - Qi-Dong Wang
- Department of Radiology, The First Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310003, China
| | - Wen-Bo Xiao
- Department of Radiology, The First Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310003, China
| | - Jing-Feng Zhang
- Department of Radiology, The First Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310003, China
| | | | - Zhong-Qiu Wang
- Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China,
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