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Vanoli A, Piva N, Inzani FS, Grillo F, Klersy C, Uccella S, Spaggiari P, Albarello L, Schiavo Lena M, Milione M, Antoniacomi C, Milanetto AC, Zerbi A, Di Sabatino A, Falconi M, Anderloni A, Mattiolo P, Luchini C, Scarpa A, Fassan M, Parente P, Luinetti O, Rindi G, Paulli M, La Rosa S. Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases. Endocr Pathol 2025; 36:18. [PMID: 40347392 PMCID: PMC12065733 DOI: 10.1007/s12022-025-09861-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/28/2025] [Indexed: 05/12/2025]
Abstract
Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness. Current treatment protocols are based on functionality, tumor size, and location, but small NF-Duo-NETs may also have metastatic potential. We aimed to investigate whether tumor cell subtyping, based on hormone expression, could provide further insights into NF-Duo-NET biological behavior. We analyzed the clinico-pathological correlates of hormone expression in a multicenter series of 151 NF-Duo-NETs, subdividing tumors into five subtypes: gastrin-producing G-cell NETs (Gas-NETs), somatostatin-producing D-cell NETs (Som-NETs), serotonin-producing enterochromaffin-cell NETs (Ser-NETs), plurihormonal NETs, and gastrin-, somatostatin-, and serotonin-negative NETs (GSSN-NETs). Som-NETs were the most frequent (31%), followed by plurihormonal NETs (26%), Gas-NETs (24%), GSSN-NETs (13%), and Ser-NETs (4%). Som-NETs and GSSN-NETs were more commonly located in the ampullary region and showed significantly larger size, more frequent lymphatic and/or vascular invasion, and higher pT, pN, and American Joint Committee on Cancer (AJCC-9th edition) stages compared to Gas-NETs, which were often (77%) diagnosed at AJCC stage I. Ampullary Som-NETs showed a more invasive and metastatic potential compared to non-ampullary Som-NETs, while, among plurihormonal NETs, the predominantly expressed hormone influenced tumor biological features, with gastrin-predominant NETs showing less invasive potential. At logistic regression, both tumor cell subtype and tumor size were independently associated with aggressiveness (pT3, pN1, or pM1 stage at diagnosis). Hormonal expression profiling may be clinically relevant in NF-Duo-NETs, independently of tumor size.
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Affiliation(s)
- Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Via Carlo Forlanini 16, 27100, Pavia, Italy.
- Anatomic Pathology, Fondazione IRCCS San Matteo Hospital, Pavia, Italy.
| | - Nestor Piva
- Anatomic Pathology Department, Federal University of São Paulo, São Paulo, Brazil
| | - Frediano Socrate Inzani
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Via Carlo Forlanini 16, 27100, Pavia, Italy
- Anatomic Pathology, Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Federica Grillo
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genova, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Catherine Klersy
- Biostatistics & Clinical Trial Center, Research Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Silvia Uccella
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Department of Pathology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Paola Spaggiari
- Department of Pathology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Luca Albarello
- Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Massimo Milione
- Department of Pathology and Laboratory Medicine, First Division of Pathology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Caterina Antoniacomi
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Via Carlo Forlanini 16, 27100, Pavia, Italy
| | - Anna Caterina Milanetto
- Pancreatic and Digestive Endocrine Surgical Research Group, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- UniCamillus - International Medical University, Rome, Italy
| | - Alessandro Zerbi
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
- Pancreatic Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- First Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy
| | - Massimo Falconi
- Vita-Salute San Raffaele University, Milan, Italy
- Pancreatic and Transplant Surgery Unit, Pancreas Translational and Clinical Research Centre, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Andrea Anderloni
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Paola Mattiolo
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
- ARC-Net Research Centre, University of Verona, Verona, Italy
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
- ARC-Net Research Centre, University of Verona, Verona, Italy
| | - Matteo Fassan
- Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
- Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Foggia, Italy
| | - Ombretta Luinetti
- Anatomic Pathology, Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Guido Rindi
- Section of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
- Anatomic Pathology Unit, Department of Woman and Child Health Sciences and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- ENETS Center of Excellence Fondazione Policlinico Universitario A. Gemelli IRCCS-Università Cattolica del Sacro Cuore, Rome, Italy
| | - Marco Paulli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Via Carlo Forlanini 16, 27100, Pavia, Italy
- Anatomic Pathology, Fondazione IRCCS San Matteo Hospital, Pavia, Italy
| | - Stefano La Rosa
- Pathology Unit, Department of Medicine and Technological Innovation, University of Insubria, Varese, Italy
- Pathology Unit, Department of Oncology, ASST Sette Laghi, Varese, Italy
- Hereditary Cancer Research Center, University of Insubria, Varese, Italy
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Kenney LM, Hughes M. Surgical Management of Gastroenteropancreatic Neuroendocrine Tumors. Cancers (Basel) 2025; 17:377. [PMID: 39941746 PMCID: PMC11816225 DOI: 10.3390/cancers17030377] [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: 12/14/2024] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from enterochromaffin cells that can arise from the gastrointestinal (GI) tract and pancreas. Surgical management is the cornerstone of treatment, with the optimal approach tailored by tumor grade, size, location, and presence of metastasis. This review discusses the current strategies for the surgical management of NETs of the gastroenteropancreatic tract. METHODS A review of the available literature was conducted to evaluate surgical approaches to NETs. Consensus guidelines were incorporated to synthesize evidence-based recommendations. RESULTS For gastric NETs, surgical approach depends on Rindi Classification, WHO grade, and tumor size, with endoscopic approaches favored for smaller and low-grade lesions. Small bowel NETs can be multifocal and thus often require a surgical approach with careful evaluation of the entire intestine. Pancreatic NETs are categorized as functional or non-functional, with enucleation or formal resection strategies based on size, location, functional status, and risk of malignancy. Colorectal NETs are primarily treated with transanal localized or formal surgical resection, depending on lesion size and depth of invasion or presence of lymph node involvement. Appendiceal NETs are either treated with appendectomy or right hemicolectomy, depending on the size, location, and invasiveness of the lesions. For metastatic NETs, cytoreduction, liver transplantation, and targeted therapies offer symptom relief and possible survival benefits. CONCLUSIONS Surgical resection provides curative potential for localized NETs and symptom control in metastatic cases. Future research is essential to refine guidelines for intermediate-risk lesions and multifocal tumors, ensuring optimal outcomes for patients with gastroenteropancreatic NETs.
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Affiliation(s)
- Lisa M. Kenney
- Department of Surgery, Eastern Virginia Medical School, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, 825 Fairfax Avenue, Suite 610, Norfolk, VA 23507, USA;
| | - Marybeth Hughes
- Department of Surgery, Division of Surgical Oncology, Eastern Virginia Medical School, Macon and Joan Brock Virginia Health Sciences at Old Dominion University, 825 Fairfax Avenue, Suite 610, Norfolk, VA 23507, USA
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De Cristofaro E, Rivory J, Walter T, Jacques J, Wallenhorst T, Lafeuille P, Pioche M. Duodenal neuroendocrine tumor successfully removed by endoscopic submucosal dissection with adaptative traction device. Endoscopy 2024; 56:E317-E318. [PMID: 38593998 PMCID: PMC11003804 DOI: 10.1055/a-2291-9448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Affiliation(s)
- Elena De Cristofaro
- Gastroenterology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
| | - Jérôme Rivory
- Gastroenterology and Endoscopy Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | - Thomas Walter
- Department of Medical Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | - Jérémie Jacques
- Gastroenterology and Endoscopy Unit, Dupuytren University Hospital, Limoges, France
| | - Timothée Wallenhorst
- Gastroenterology and Endoscopy Unit, Pontchaillou University Hospital, Rennes, France
| | - Pierre Lafeuille
- Gastroenterology and Endoscopy Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | - Mathieu Pioche
- Gastroenterology and Endoscopy Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
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Hers F, Klümpen HJ, Dreijerink KMA, Engelsman AF, Nieveen van Dijkum EJM, Kaçmaz E. Endoscopic versus surgical resection of duodenal neuroendocrine neoplasms between 10 and 20 mm: A multi-centered retrospective cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108596. [PMID: 39213696 DOI: 10.1016/j.ejso.2024.108596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 07/31/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION Recommendations for resection technique of duodenal neuroendocrine neoplasms (D-NEN) with a size between 10 and 20 mm are lacking. The primary aim was to compare overall survival (OS) and progression-free survival (PFS) after endoscopic resection (ER) with surgical resection (SR). The secondary aim was to assess the incidence and clinical variables correlated with OS. METHODS Data of patients with D-NENs between 2008 and 2018 were extracted from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank. RESULTS A total of 259 patients were identified, of which 138 were included: 98 (68 %) underwent ER and 44 patients (32 %) underwent SR. Of these, 38 patients had D-NENs sized between 10 and 20 mm. ER Patients were more frequently male and had a lower T-stage and tumour size than SR patients (all P < 0.05). Positive resection margins were observed more frequently after ER compared to SR (71 % vs 15 %, P < 0.005). No patients with tumours between 10 and 20 mm died after ER or SR (median follow-up 71.8 vs. 52.0 months). PFS rates were not significantly different after ER compared to SR (P = 0.672). Recurrence rates were 13 % for ER and 7 % for SR (P = 0.604). CONCLUSION Between 2008 and 2018, the incidence increased from 0.06 to 0.11 per 100,000 patients per year. OS after ER or SR did not differ for D-NEN between 10 and 20 mm. Recurrence and PFS rates were not significantly different. These results suggest that D-NENs sized between 10 and 20 mm could potentially be treated first with ER. Future studies are needed to confirm this hypothesis.
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Affiliation(s)
- Felix Hers
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours (ACcENT), Cancer Center Amsterdam, ENETS Center of Excellence, Amsterdam, The Netherlands; Amsterdam Cancer Center, Amsterdam, The Netherlands
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours (ACcENT), Cancer Center Amsterdam, ENETS Center of Excellence, Amsterdam, The Netherlands; Amsterdam Cancer Center, Amsterdam, The Netherlands
| | - Koen M A Dreijerink
- Department of Endocrinology and Metabolism, Amsterdam UMC Location VU University, De Boelelaan 1117, Amsterdam, The Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours (ACcENT), Cancer Center Amsterdam, ENETS Center of Excellence, Amsterdam, The Netherlands; Amsterdam Cancer Center, Amsterdam, The Netherlands
| | - Anton F Engelsman
- Amsterdam Center for Endocrine and Neuroendocrine Tumours (ACcENT), Cancer Center Amsterdam, ENETS Center of Excellence, Amsterdam, The Netherlands; Amsterdam Cancer Center, Amsterdam, The Netherlands; Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, de Boelelaan 1117, 1081HV, Amsterdam, The Netherlands
| | - Els J M Nieveen van Dijkum
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours (ACcENT), Cancer Center Amsterdam, ENETS Center of Excellence, Amsterdam, The Netherlands; Amsterdam Cancer Center, Amsterdam, The Netherlands
| | - Enes Kaçmaz
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Center for Endocrine and Neuroendocrine Tumours (ACcENT), Cancer Center Amsterdam, ENETS Center of Excellence, Amsterdam, The Netherlands; Amsterdam Cancer Center, Amsterdam, The Netherlands.
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Shaikh SD, Jacoba I, Sun N, Chung E, Kim HT, Zhao Q, Weber HC. A Clinicopathological Appraisal of Duodenal Neuroendocrine Tumors at a Racially Diverse Safety Net Hospital. Am J Gastroenterol 2024:00000434-990000000-01033. [PMID: 38345246 DOI: 10.14309/ajg.0000000000002722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 01/15/2024] [Indexed: 03/20/2024]
Abstract
INTRODUCTION Significant knowledge gaps exist regarding clinicopathological profiling as well as treatment, surveillance, and survival of duodenal neuroendocrine tumors (dNETs). METHODS We clinicopathologically characterized and identified racial differences among patients with dNETs at a large safety net hospital. Tumor grades were updated based on the World Health Organization 2019 NET classification, and overall survival was determined. RESULTS We identified 17 dNETs and found no differences in clinicopathologic characteristics across racial groups. Pathological diagnosis was upgraded in 35% of dNETs, and age >65 years significantly shortened overall survival. DISCUSSION Larger-scale studies are needed to determine the significance of these findings.
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Affiliation(s)
- Sofia D Shaikh
- Section of General Internal Medicine, Boston Medical Center, Boston, Massachusetts, USA
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Isa Jacoba
- Department of Pathology & Laboratory Medicine, Boston Medical Center, Boston, Massachusetts, USA
| | - Natalie Sun
- Section of General Internal Medicine, Boston Medical Center, Boston, Massachusetts, USA
| | - Enoch Chung
- Division of General Internal Medicine, Massachusetts General Hospital, Boston MA USA
| | - Haesook T Kim
- Dana-Farber Cancer Institute, Department of Data Science, Boston, Massachusetts, USA
| | - Qing Zhao
- Department of Pathology & Laboratory Medicine, Boston Medical Center, Boston, Massachusetts, USA
| | - H Christian Weber
- Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
- Department of Pathology & Laboratory Medicine, Boston Medical Center, Boston, Massachusetts, USA
- Section of Gastroenterology & Hepatology, Boston Medical Center, Boston, Massachusetts, USA
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Le NTB, Park SJ, Cho BJ, Yang MA, Song JS, Lee WD, Ju MJ, Cho JW. Successful Endoscopic Submucosal Dissection Using Open Peroral Endoscopic Myotomy for Duodenal Neuroendocrine Tumor. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2024; 83:61-64. [PMID: 38389462 DOI: 10.4166/kjg.2023.145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 12/21/2023] [Accepted: 12/27/2023] [Indexed: 02/24/2024]
Abstract
Duodenal neuroendocrine tumors (NETs) are subepithelial tumors that are difficult to remove endoscopically, particularly when located just beyond the pylorus. This paper reports a case of a successful endoscopic submucosal dissection (ESD) using open gastric peroral endoscopic myotomy (POEM) for a remnant duodenal NET detected after endoscopic mucosal resection (EMR). A 67-year-old male presented with a 5 mm remnant duodenal NET close to the pylorus after EMR for a duodenal polypoid lesion performed four months earlier. Duodenal ESD was performed under conscious sedation using I-type and IT II knives. The tumor adhered to the fibrotic tissue, and the submucosal cushion was insufficient. Open gastric POEM was performed concurrently during ESD, resulting in the complete resection of the NET. This case suggests that while challenging, open gastric POEM can serve as a valuable technique for endoscopic resection in cases of early gastric cancer or duodenal masses located around the pylorus.
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Affiliation(s)
- Ngoc Thi Bao Le
- Department of Gastroenterology and Hepatology, Quang Nam General Hospital, Quang Nam, Vietnam
| | - Sang Jin Park
- Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea
| | - Bong Ju Cho
- Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea
| | - Min A Yang
- Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea
| | - Jae Sun Song
- Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea
| | - Won Dong Lee
- Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea
| | - Myoung Jin Ju
- Department of Pathology, Presbyterian Medical Center, Jeonju, Korea
| | - Jin Woong Cho
- Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea
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Mirzaie S, Park JY, Mederos MA, Girgis MD. Surgical and Endoscopic Resection of Duodenal Neuroendocrine Tumors Have Similar Disease-Specific Survival Outcome. J Gastrointest Surg 2023; 27:2365-2372. [PMID: 37552388 PMCID: PMC10661787 DOI: 10.1007/s11605-023-05800-y] [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: 05/28/2023] [Accepted: 07/21/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND Duodenal neuroendocrine tumors (dNETs) are rare, and their management is not well-defined. National Comprehensive Cancer Network (NCCN) guidelines recommend surgical resection of large dNETs (> 2 cm) and endoscopic resection of small tumors (< 2 cm). We compared the survival outcomes between surgical and endoscopic resection in various dNET sizes. METHODS A retrospective cohort study was conducted using patient data from Surveillance, Epidemiology, and End Results Program (SEER) database. Variables analyzed included age, tumor size, grade, stage, and lymph node status. Disease-specific survival (DSS) was compared for endoscopic and surgical groups in dNET size strata: 0-0.5, 0.5-1, 1-2, 2-3, and > 3 cm. Kaplan-Meier and multivariable Cox proportional hazards models were used for survival analysis. RESULTS The study included 465 patients, with 124 (26.7%) undergoing surgical resection. The average age was 61.9 years, and tumor sizes ranged from 0.1 to 10.5 cm. Endoscopic resection had 40.5% of tumors between 0 and 0.5 cm, while surgery had only 21% (p < 0.001). In the surgical cohort, 79.8% had grade 1 tumors compared to 88.3% in the endoscopy group (P = 0.024). Among surgically resected cases, 48.4% (60 patients) had lymph node involvement. Age, tumor size, grade, and stage did not significantly predict survival after surgical resection. Stratified by tumor size, no difference in DSS was observed between surgery and endoscopy groups. CONCLUSIONS Endoscopic resection demonstrated similar survival outcomes to surgical resection across dNET sizes in this national analysis. Given the risks and the lack of survival benefits for surgery, endoscopic resection may be beneficial for both small and large tumors. Further studies are warranted to validate the current NCCN guidelines.
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Affiliation(s)
- Sarah Mirzaie
- David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
| | - Joon Y Park
- Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Michael A Mederos
- Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
| | - Mark D Girgis
- David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
- Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
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Kmiotek E, Lakda S, Borakati A, Ogunbiyi O, Mandair D, Caplin M, Toumpanakis C, Mirnezami R. Management Strategies and Outcomes for Small Intestinal Neuroendocrine Tumours with Involvement of the Superior Mesenteric Vessels: A Systematic Review. Curr Oncol 2023; 30:9192-9204. [PMID: 37887564 PMCID: PMC10605700 DOI: 10.3390/curroncol30100664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/26/2023] [Accepted: 10/14/2023] [Indexed: 10/28/2023] Open
Abstract
Small intestinal neuroendocrine tumours (SI-NETs) are the most common small intestinal tumours. A particularly challenging subset of these tumours is those that involve the superior mesenteric artery or vein for which the role and feasibility of surgery are often questioned. This systematic review aimed to identify and evaluate the management strategies used for these complex SI-NETs. The identified studies showed positive outcomes with surgery and multimodality therapy.
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Affiliation(s)
- Elizabeth Kmiotek
- Department of Colorectal Surgery, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK (O.O.)
| | - Sakina Lakda
- University College London Medical School, 74 Huntley Street, London WC1E 6DE, UK;
| | - Aditya Borakati
- Division of Surgery and Interventional Science, University College London, Royal Free Hospital Campus, 9th Floor, Pond Street, Hampstead, London NW3 2QG, UK;
| | - Olagunju Ogunbiyi
- Department of Colorectal Surgery, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK (O.O.)
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
| | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
| | - Reza Mirnezami
- Department of Colorectal Surgery, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK (O.O.)
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK; (D.M.); (M.C.); (C.T.)
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Malladi UD, Chimata SK, Bhashyakarla RK, Lingampally SR, Venkannagari VR, Mohammed ZA, Vargiya RV. Duodenal neuroendocrine tumor-tertiary care centre experience: A case report. World J Transl Med 2023; 11:1-8. [DOI: 10.5528/wjtm.v11.i1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 07/05/2023] [Accepted: 08/17/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms arising from neuroendocrine cells, which contribute a small fraction of gastrointestinal malignancies. Duodenal neuroendocrine tumors (dNETs) represent 2% of all gastroenteropancreatic NENs. NENs are heterogeneous in terms of clinical symptoms, location, and prognosis. Non-functional NETs are mostly asymptomatic and need a high degree of clinical suspicion. Diagnosis of NETs is by endoscopic, endosonographic biopsy, and histopathological examination with immunohistochemistry staining for synaptophysin and chromogranin A.
CASE SUMMARY We present case reports of 5 patients obtained over a period of 10 years in our center with dNETs. One patient had moderately differentiated NET and the remaining four had well-differentiated NET. Surveillance endoscopy was recommended in all the patients and is kept under regular follow-up after performing endoscopic therapy using endoscopic mucosal resection in 4 of them and one patient was advised to undergo a Whipple procedure.
CONCLUSION Recently, the number of reported cases of NETs has increased due to advancements in diagnostic modalities and prevalence because of longer survival duration. The management differs based on the site, size, proliferation grade, and locally invasive pattern. They are slow-growing tumors with a good overall prognosis. The prognosis correlates with local lymph node status and metastasis.
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Affiliation(s)
- Uma Devi Malladi
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Suraj Kumar Chimata
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Ramesh Kumar Bhashyakarla
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Sahitya Reddy Lingampally
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Vikas Reddy Venkannagari
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Zeeshan Ali Mohammed
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Rahul Vijay Vargiya
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
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Gopakumar H, Jahagirdar V, Koyi J, Dahiya DS, Goyal H, Sharma NR, Perisetti A. Role of Advanced Gastrointestinal Endoscopy in the Comprehensive Management of Neuroendocrine Neoplasms. Cancers (Basel) 2023; 15:4175. [PMID: 37627203 PMCID: PMC10453187 DOI: 10.3390/cancers15164175] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 08/15/2023] [Accepted: 08/15/2023] [Indexed: 08/27/2023] Open
Abstract
Neuroendocrine neoplasms (NENs), also called neuroendocrine tumors (NETs), are relatively uncommon, heterogenous tumors primarily originating in the gastrointestinal tract. With the improvement in technology and increasing use of cross-sectional imaging and endoscopy, they are being discovered with increasing frequency. Although traditionally considered indolent tumors with good prognoses, some NENs exhibit aggressive behavior. Timely diagnosis, risk stratification, and management can often be a challenge. In general, small NENs without local invasion or lymphovascular involvement can often be managed using minimally invasive advanced endoscopic techniques, while larger lesions and those with evidence of lymphovascular invasion require surgery, systemic therapy, or a combination thereof. Ideal management requires a comprehensive and accurate understanding of the stage and grade of the tumor. With the recent advancements, a therapeutic advanced endoscopist can play a pivotal role in diagnosing, staging, and managing this rare condition. High-definition white light imaging and digital image enhancing technologies like narrow band imaging (NBI) in the newer endoscopes have improved the diagnostic accuracy of traditional endoscopy. The refinement of endoscopic ultrasound (EUS) over the past decade has revolutionized the role of endoscopy in diagnosing and managing various pathologies, including NENs. In addition to EUS-directed diagnostic biopsies, it also offers the ability to precisely assess the depth of invasion and lymphovascular involvement and thus stage NENs accurately. EUS-directed locoregional ablative therapies are increasingly recognized as highly effective, minimally invasive treatment modalities for NENs, particularly pancreatic NENs. Advanced endoscopic resection techniques like endoscopic submucosal dissection (ESD), endoscopic submucosal resection (EMR), and endoscopic full-thickness resection (EFTR) have been increasingly used over the past decade with excellent results in achieving curative resection of various early-stage gastrointestinal luminal lesions including NENs. In this article, we aim to delineate NENs of the different segments of the gastrointestinal (GI) tract (esophagus, gastric, pancreatic, and small and large intestine) and their management with emphasis on the endoscopic management of these tumors.
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Affiliation(s)
- Harishankar Gopakumar
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA;
| | - Vinay Jahagirdar
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; (V.J.); (J.K.)
| | - Jagadish Koyi
- Department of Internal Medicine, University of Missouri-Kansas City, Kansas City, MO 64110, USA; (V.J.); (J.K.)
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, USA;
| | - Hemant Goyal
- Department of Surgery, Center for Interventional Gastroenterology at UT (iGUT), The University of Texas Health Science Center, Houston, TX 77054, USA;
| | - Neil R. Sharma
- Advanced Interventional Endoscopy & Endoscopic Oncology (IOSE) Division, GI Oncology Tumor Site Team, Parkview Cancer Institute, 11104 Parkview Circle, Suite 310, Fort Wayne, IN 46845, USA;
| | - Abhilash Perisetti
- Division of Gastroenterology and Hepatology, Kansas City Veteran Affairs, Kansas City, MO 64128, USA
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11
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Sultana Q, Kar J, Verma A, Sanghvi S, Kaka N, Patel N, Sethi Y, Chopra H, Kamal MA, Greig NH. A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management. J Clin Med 2023; 12:5138. [PMID: 37568540 PMCID: PMC10420169 DOI: 10.3390/jcm12155138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/01/2023] [Accepted: 08/02/2023] [Indexed: 08/13/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or peptide hormone secretion, impacting their quality of life and prognosis. Over the last decade, pathologic categorization, diagnostic techniques and therapeutic choices for NENs-both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs)-have appreciably evolved. Diagnosis of NEN mostly follows a suspicion from clinical features or incidental imaging findings. Hormonal or non-hormonal biomarkers (like serum serotonin, urine 5-HIAA, gastrin and VIP) and histology of a suspected NEN is, therefore, critical for both confirmation of the diagnosis and classification as an NET or NEC. Therapy for NENs has progressed recently based on a better molecular understanding, including the involvement of mTOR, VEGF and peptide receptor radionuclide therapy (PRRT), which add to the growing evidence supporting the possibility of treatment beyond complete resection. As the incidence of NENs is on the rise in the United States and several other countries, physicians are more likely to see these cases, and their better understanding may support earlier diagnosis and tailoring treatment to the patient. We have compiled clinically significant evidence for NENs, including relevant changes to clinical practice that have greatly updated our diagnostic and therapeutic approach for NEN patients.
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Affiliation(s)
- Qamar Sultana
- Department of Medicine, Deccan College of Medical Sciences, Hyderabad 500058, India;
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
| | - Jill Kar
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, Lady Hardinge Medical College, New Delhi 110001, India
| | - Amogh Verma
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Rama Medical College Hospital and Research Centre, Hapur 245304, India
| | - Shreya Sanghvi
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Lokmanya Tilak Municipal Medical College and General Hospital, Mumbai 400022, India
| | - Nirja Kaka
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, GMERS Medical College, Himmatnagar 390021, India
| | - Neil Patel
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Department of Medicine, GMERS Medical College, Himmatnagar 390021, India
| | - Yashendra Sethi
- PearResearch, Dehradun 248001, India; (J.K.); (A.V.); (S.S.); (N.K.); (N.P.)
- Government Doon Medical College, HNB Uttarakhand Medical Education University, Dehradun 248001, India
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, India;
| | - Mohammad Amjad Kamal
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China;
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1216, Bangladesh
- Enzymoics, Hebersham, NSW 2770, Australia
- Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia
| | - Nigel H. Greig
- Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
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12
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Panzuto F, Ramage J, Pritchard DM, van Velthuysen MLF, Schrader J, Begum N, Sundin A, Falconi M, O'Toole D. European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for gastroduodenal neuroendocrine tumours (NETs) G1-G3. J Neuroendocrinol 2023; 35:e13306. [PMID: 37401795 DOI: 10.1111/jne.13306] [Citation(s) in RCA: 60] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 05/09/2023] [Accepted: 05/10/2023] [Indexed: 07/05/2023]
Abstract
The aim of the present guidance paper was to update the previous ENETS guidelines on well-differentiated gastric and duodenal neuroendocrine tumours (NETs), providing practical guidance for specialists in the diagnosis and management of gastroduodenal NETs. Type II gastric NETs, neuroendocrine carcinomas (NECs), and functioning duodenal NETs are not covered, since they will be discussed in other ENETS guidance papers.
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Affiliation(s)
- Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy
| | - John Ramage
- Department of Gastroenterology, Hampshire Hospitals and ENETS Center, Kings Health Partners London, London, United Kingdom
| | - D Mark Pritchard
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | | | - Joerg Schrader
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Nehara Begum
- Department for General-, Visceral-, Thoracic- and Endocrine Surgery, Johannes-Wesling-Klinikum Minden, University Hospital of the Ruhr-University Bochum, Bochum, Germany
| | - Anders Sundin
- Department of Surgical Sciences, Radiology & Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Massimo Falconi
- Pancreas Translational and Clinical Research Center, Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Dermot O'Toole
- National Centre for Neuroendocrine Tumours, ENETS Centre of Excellence, St. Vincent's University Hospital, Dublin, Ireland
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13
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Chetcuti Zammit S, Sidhu R. Small bowel neuroendocrine tumours - casting the net wide. Curr Opin Gastroenterol 2023; 39:200-210. [PMID: 37144538 DOI: 10.1097/mog.0000000000000917] [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: 05/06/2023]
Abstract
PURPOSE OF REVIEW Our aim is to provide an overview of small bowel neuroendocrine tumours (NETs), clinical presentation, diagnosis algorithm and management options. We also highlight the latest evidence on management and suggest areas for future research. RECENT FINDINGS Dodecanetetraacetic acid (DOTATATE) scan can detect NETs with an improved sensitivity than when compared with an Octreotide scan. It is complimentary to small bowel endoscopy that provides mucosal views and allows the delineation of small lesions undetectable on imaging. Surgical resection is the best management modality even in metastatic disease. Prognosis can be improved with the administration of somatostatin analogues and Evarolimus as second-line therapies. SUMMARY NETs are heterogenous tumours affecting most commonly the distal small bowel as single or multiple lesions. Their secretary behaviour can lead to symptoms, most commonly diarrhoea and weight loss. Metastases to the liver are associated with carcinoid syndrome.
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Affiliation(s)
| | - Reena Sidhu
- Academic Department of Gastroenterology, Royal Hallamshire Hospital, Department of Infection, Immunity and Cardiovascular Diseases, University of Sheffield, Sheffield, UK
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14
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Kim GH, Yi K, Joo DC, Lee MW, Jeon HK, Lee BE. Magnifying Endoscopy with Narrow-Band Imaging for Duodenal Neuroendocrine Tumors. J Clin Med 2023; 12:3106. [PMID: 37176547 PMCID: PMC10179496 DOI: 10.3390/jcm12093106] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/17/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Duodenal neuroendocrine tumors (NETs) are rare subepithelial tumors that arise from the neuroendocrine cells beneath the epithelial layer. However, an accurate histopathological diagnosis is difficult when tissue samples are obtained using conventional endoscopic forceps biopsy alone. This study aimed to evaluate the magnifying endoscopy with narrow-band imaging (ME-NBI) findings of duodenal NETs. We retrospectively analyzed a database of 22 duodenal NETs from 21 patients who underwent ME-NBI between January 2011 and June 2022. The ME-NBI, endosonographic, and histopathologic findings of duodenal NETs were analyzed. Nineteen lesions were located in the bulb, two were located in the superior duodenal angle, and one was located in the second portion of the duodenum. Eighteen lesions (82%) had IIa morphology, and nine (41%) had central depression on the surface. On endoscopic ultrasonography, almost all lesions (20/22, 91%) were located in the second and/or third layers, and the median tumor size was 6 mm. During ME-NBI, the microsurface pattern was regular in 18 lesions (82%) and absent in 4 (18%). The microvascular pattern was regular in 17 lesions (77%), irregular in 4 (18%), and absent in 1 (5%). Thickened subepithelial vessels were observed in 15 (68%) lesions. There was no difference in tumor size according to the presence or absence of thickened subepithelial vessels (6.1 ± 1.8 mm vs. 5.9 ± 3.8 mm, p = 0.860). In conclusion, the characteristic ME-NBI findings of duodenal NETs were regular microsurface and microvascular patterns and the presence of thickened subepithelial vessels. These ME-NBI features may be useful for differentiating duodenal NETs from other duodenal subepithelial lesions.
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Affiliation(s)
- Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 49241, Republic of Korea; (K.Y.); (D.C.J.); (M.W.L.); (H.K.J.)
- Biomedical Research Institute, Pusan National University Hospital, Busan 49241, Republic of Korea
| | - Kiyoun Yi
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 49241, Republic of Korea; (K.Y.); (D.C.J.); (M.W.L.); (H.K.J.)
| | - Dong Chan Joo
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 49241, Republic of Korea; (K.Y.); (D.C.J.); (M.W.L.); (H.K.J.)
| | - Moon Won Lee
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 49241, Republic of Korea; (K.Y.); (D.C.J.); (M.W.L.); (H.K.J.)
| | - Hye Kyung Jeon
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 49241, Republic of Korea; (K.Y.); (D.C.J.); (M.W.L.); (H.K.J.)
| | - Bong Eun Lee
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 49241, Republic of Korea; (K.Y.); (D.C.J.); (M.W.L.); (H.K.J.)
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15
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Ito T, Ramos-Alvarez I, Jensen RT. Successful Lifetime/Long-Term Medical Treatment of Acid Hypersecretion in Zollinger-Ellison Syndrome (ZES): Myth or Fact? Insights from an Analysis of Results of NIH Long-Term Prospective Studies of ZES. Cancers (Basel) 2023; 15:1377. [PMID: 36900170 PMCID: PMC10000208 DOI: 10.3390/cancers15051377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/09/2023] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Analysis of the efficacy/pharmacology of long-term/lifetime medical treatment of acid hypersecretion in a large cohort of ZES patients in a prospective study. This study includes the results from all 303 patients with established ZES who were prospectively followed and received acid antisecretory treatment with either H2Rs or PPIs, with antisecretory doses individually titrated by the results of regular gastric acid testing. The study includes patients treated for short-term periods (<5 yrs), patients treated long-term (>5 yrs), and patients with lifetime treatment (30%) followed for up to 48 years (mean 14 yrs). Long-term/lifelong acid antisecretory treatment with H2Rs/PPIs can be successfully carried out in all patients with both uncomplicated and complicated ZES (i.e., with MEN1/ZES, previous Billroth 2, severe GERD). This is only possible if drug doses are individually set by assessing acid secretory control to establish proven criteria, with regular reassessments and readjustments. Frequent dose changes both upward and downward are needed, as well as regulation of the dosing frequency, and there is a primary reliance on the use of PPIs. Prognostic factors predicting patients with PPI dose changes are identified, which need to be studied prospectively to develop a useful predictive algorithm that could be clinically useful for tailored long-term/lifetime therapy in these patients.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | | | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA
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16
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Stan-Ilie M, Şandru V, Plotogea OM, Rînja E, Pavel C, Constantinescu G, Negreanu L, Paduraru DN, Bolocan A, Andronic O, Davitoiu D, Bălan GG, Constantinescu A. Duodenal Gangliocytic Paragangliomas-Case Series and Literature Review. Life (Basel) 2023; 13:597. [PMID: 36983753 PMCID: PMC10058500 DOI: 10.3390/life13030597] [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: 01/10/2023] [Revised: 02/12/2023] [Accepted: 02/16/2023] [Indexed: 02/23/2023] Open
Abstract
Duodenal gangliocytic paragangliomas are rare neuroendocrine tumors primarily localized in the periampullary area. Though mostly asymptomatic, they can present with various symptoms, most often jaundice, anemia and abdominal pain. The present paper is a case series report, describing our personal experience with patients presenting to the Emergency Unit with different symptoms due to duodenal gangliocytic paraganglioma. Endoscopic resection is safe and indicated in most of the cases, being also associated with lower medical costs. EUS plays a central role in the pre-resection management and in surveillance, and immunostaining is decisive to ascertain the tumor histologic origin. In addition to reporting our experience, we researched the literature regarding these rare tumors and performed a comprehensive review.
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Affiliation(s)
- Madalina Stan-Ilie
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Vasile Şandru
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Oana-Mihaela Plotogea
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Ecaterina Rînja
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Christopher Pavel
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Gabriel Constantinescu
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Lucian Negreanu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Dan Nicolae Paduraru
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Alexandra Bolocan
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Octavian Andronic
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Dragos Davitoiu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Surgery, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
| | - Gheorghe G. Bălan
- Department of Gastroenterology, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania
| | - Alexandru Constantinescu
- Department 5, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Gastroenterology, University Emergency Hospital Bucharest, 050098 Bucharest, Romania
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17
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Muacevic A, Adler JR, Farraj M, Kaliounji H, Farraj KL. A Rare Presentation of a Duodenal Neuroendocrine Tumor. Cureus 2023; 15:e33747. [PMID: 36788876 PMCID: PMC9922524 DOI: 10.7759/cureus.33747] [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] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
Neuroendocrine tumors (NETs), which are a rare type of tumor, are defined as epithelial cells with predominantly neuroendocrine differentiation and consist of a spectrum of tumors emerging from stem cells throughout the body and can occur anywhere in the body. While they are rare, the incidence over the past few decades has increased. Here we present a case of a 64-year-old female who was incidentally found to have a duodenal neuroendocrine tumor. The patient initially presented to the emergency department secondary to syncope and collapse. During her trauma evaluation, an incidental lobulated soft tissue mass inferior to the distal stomach was seen on complete computed tomography (CT) scans. The surgery team was consulted for resection of the mass and an octreotide scan was performed prior to resection to further evaluate the mass and to check for any signs of metastatic disease. The octreotide scan demonstrated intense radiotracer accumulation within the duodenal mass consistent with a neuroendocrine tumor and no areas of abnormal radiotracer accumulation suspicious for metastatic disease. Pathology of the resected mass was positive for a well-differentiated neuroendocrine tumor with an organoid pattern and homogenous oval-round neoplastic cells with a salt-pepper nuclear and pseudo glandular arrangement that was well-circumscribed and partially encapsulated with negative margins. Immunohistochemistry was positive for AE ⅓, CD56, Synaptophysin, and chromogranin and negative for CD117, DOG-1, CD34, and CD45. The prevalence of NETs has increased over the years due to the improvement in diagnostic tools, such as upper gastrointestinal endoscopy. In addition to the fact that the duodenum is a rare location for such tumors, neuroendocrine tumors are also typically found in those under 50 years old. However, our patient was found to have both a duodenal mass and was over the age of 50 at the time of presentation and diagnosis. To date, a consensus on a conclusive treatment of duodenal NETs (D-NETs) has not been reached. This case brings to light the importance of further research in diagnosing and treating neuroendocrine tumors and also raises awareness for clinicians to have this in their differential.
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18
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Koffas A, Giakoustidis A, Papaefthymiou A, Bangeas P, Giakoustidis D, Papadopoulos VN, Toumpanakis C. Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. Front Surg 2023; 10:1064145. [PMID: 36950054 PMCID: PMC10025557 DOI: 10.3389/fsurg.2023.1064145] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 02/07/2023] [Indexed: 03/08/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.
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Affiliation(s)
- Apostolos Koffas
- Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Correspondence: Apostolos Koffas
| | - Alexandros Giakoustidis
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Apostolis Papaefthymiou
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London, United Kingdom
| | - Petros Bangeas
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Giakoustidis
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Vasileios N Papadopoulos
- 1st Department of Surgery, General Hospital Papageorgiou, School of Medicine, Faculty of Medical Sciences, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Christos Toumpanakis
- Centre for Gastroenterology, Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, United Kingdom
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19
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Small bowel neuroendocrine neoplasm: what surgeons want to know. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:4005-4015. [PMID: 35312820 DOI: 10.1007/s00261-022-03485-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/01/2022] [Accepted: 03/02/2022] [Indexed: 01/18/2023]
Abstract
Neuroendocrine neoplasms of the small bowel are a diverse group of tumors with a broad spectrum of imaging findings and clinical implications. Most tumors originate in close proximity to the ileocecal valve and most commonly metastasize to the mesentery and liver. This review will highlight the imaging findings of primary and metastatic small bowel neuroendocrine neoplasm that are most relevant to the surgical team.
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20
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El Bakouri A, El wassi A, Eddaoudi Y, Bouali M, EL Hattabi K, Bensardi F, Fadil A. Fortuitous discovery of an early neuroendocrine tumor during appendicular peritonitis. Ann Med Surg (Lond) 2022; 82:104735. [PMID: 36268349 PMCID: PMC9577830 DOI: 10.1016/j.amsu.2022.104735] [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: 07/25/2022] [Revised: 09/18/2022] [Accepted: 09/18/2022] [Indexed: 11/27/2022] Open
Abstract
Introduction Neuroendocrine tumors of the small bowel are rare but represent the most frequent histological type at this level; their incidence is increasing thanks to the evolution of diagnostic means.Intestinal NETs, developed at the expense of enterochromaffin cells of the embryological midgut, are frequently associated with mesenteric lymph node dissemination and distant metastasis (liver, peritoneum). Materials and methods We report a case of Incidental discovery of a small bowel neuroendocrinetumor during appendicular peritonitis in the department of Emergency visceral surgery P35 of the ibn rochd hospital in casablanca. Results Our patient Our patient was admitted to the emergency room for generalized abdominal pain with an appendicular symptomatology evolving five days before days the consultation with clinical examination: conscious patient stable on the hemodynamic and respiratory plan The examination noted generalized abdominal defense the hernial orifices were free The biological work-up revealed a hb 13 g/dL; hyperleukocytosis with predominantly PNN at 18,300 elements/mm3,CRP was elevated to 190, renal function was normal urea 5 mmol/L creatinemia 9 mg/l an abdominal ultrasound showed a 9 mm appenndix perforated at its tip with moderate peritoneal effusion.the patient were operated in the emergency room, approached by laparotomy with the exploration we found a swollen and inflamed appenndix perforated at the level of its tip with moderate peritoneal effusion with false membranes in all the peritoneal cavity with the presence of a polyp localized at 2 m from the duodenojejunal flexur .the patient benefited from a retrograde appendectomy with peritoneal cleansing and a resection of the polyp with 1cm on each side with a Grele-grele anastomosis with the examination of the anapathomopathologist: aspect compatible with a well differentiated neuroendocrine tumor of grade 2. Conclusion Digestive NETs are rare tumors, but their incidence has increased significantly in recent years. This is due to a better knowledge of these tumors, whose diagnosis is becoming easier with the advent of new morphological and biological techniques.The intestinal location is the most frequent. The digestive surgeon must therefore be familiar with its management. An update of knowledge and collaboration between surgeons, anatomopathologists, radiologists and oncologists are necessary, Whatever their location, these tumors are on the one hand capable of producing and secreting amines and on the other hand they are characterized by a common phenotype, expression of general endocrine markers (specific neuron enolase, chromogranin) or specific endocrine markers and expression of peptide receptors such as somastotatin receptors.These tumors are most often diagnosed incidentally during the workup of aspecific digestive disorders or during hormonal hypersecretion syndrome or rarely by a complication.
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Affiliation(s)
- Abdelilah El Bakouri
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
| | - anas El wassi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Yassine Eddaoudi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Mounir Bouali
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Khalid EL Hattabi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Fatimazahra Bensardi
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
| | - Abdelaziz Fadil
- Visceral Surgery Emergency Department P35, University Hospital Center Ibn Rochd, Casablanca, Morocco
- Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco
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21
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Diagnostic features and management options for duodenal neuroendocrine neoplasms: a retrospective, multi-centre study. Sci Rep 2022; 12:15762. [PMID: 36130981 PMCID: PMC9492724 DOI: 10.1038/s41598-022-19738-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 09/02/2022] [Indexed: 11/09/2022] Open
Abstract
Duodenal neuroendocrine neoplasms (dNENs) are rare neoplasms but their incidence is on the rise. They are classified into 5 sub-types but there remains much heterogeneity in behaviour in particular of non-functioning dNENs. To retrospectively analyse outcomes for all types of dNENs, and highlight prognostic factors associated with worse outcome. 102 (57 m/45f.) patients were identified with mean age at diagnosis 62 (range 32–87) years. The majority were non-functioning tumours 87/102 and median size was 10 mm (range 0.9–130 mm). 83 patients had Stage I or II disease, of which 17 underwent endoscopic resection with R1 rate of 45% and complication rate 12%. 36 patients were kept under endoscopic surveillance. There were 11 deaths of which 4 were disease related. Age and Ki67 > 20% were associated with worse OS in all dNENs. In non-functioning dNENs Ki67 > 3% was a predictor of lymph nodes metastases with OR 18.2 (2.54–13) (p < 0.005) in univariate analyses and liver metastases with OR 6.79 (1.56–29.5) (p < 0.05) in the multivariate analysis. Lesions 11–20 mm in size had OR 11.1 (1.16–106) compared to lesions < 11 mm for the prediction of lymph node metastases in the multivariate analysis (p < 0.05). ROC analysis of size of non-functioning dNENs to predict LN metastases found < 15 mm had an AUROC of 0.9 (0.81–0.99) with a sensitivity of 85% and specificity of 88%. dNENs are increasing in incidence, however low grade and smaller lesions have an indolent course and the role of endoscopic resection and active surveillance needs to be reviewed.
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22
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Iabichino G, Di Leo M, Arena M, Rubis Passoni GG, Morandi E, Turpini F, Viaggi P, Luigiano C, De Luca L. Diagnosis, treatment, and current concepts in the endoscopic management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:4943-4958. [PMID: 36160644 PMCID: PMC9494936 DOI: 10.3748/wjg.v28.i34.4943] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 06/29/2022] [Accepted: 08/22/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors derived from the neuroendocrine cell system, which that have increased in incidence and prevalence in recent years. Despite improvements in radiological and metabolic imaging, endoscopy still plays a pivotal role in the number of GEP-NENs. Tumor detection, characterization, and staging are essential in management and treatment planning. Upper and lower gastrointestinal (GI) endoscopy is essential for correct localization of the primary tumor site of GI NENs. Endoscopic ultrasonography (EUS) has an important role in the imaging and tissue acquisition of pancreatic NENs and locoregional staging of GI neuroendocrine tumors. Correct staging and histological diagnosis have important prognostic implications. Endoscopic operating techniques allow the removal of small GI NENs in the early stage of mucosal or submucosal invasion of the intestinal wall. Preoperative EUS-guided techniques may help the surgeon locate small and deep tumors, thus avoiding formal pancreatic resections in favor of parenchymal-sparing surgery. Finally, locoregional ablative treatments have been proposed in recent studies with promising results in selected patients.
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Affiliation(s)
| | - Milena Di Leo
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Monica Arena
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | | | | | - Francesca Turpini
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Paolo Viaggi
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
| | - Carmelo Luigiano
- Gastroenterology Section, Grande Ospedale Metropolitano “Bianchi-Melacrino-Morelli”, Reggio Calabria 89124, Italy
| | - Luca De Luca
- Digestive Endoscopy Unit, ASST Santi Paolo e Carlo, Milano 20144, Italy
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23
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Fernandes CJ, Leung G, Eads JR, Katona BW. Gastroenteropancreatic Neuroendocrine Tumors. Gastroenterol Clin North Am 2022; 51:625-647. [PMID: 36153114 DOI: 10.1016/j.gtc.2022.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.
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Affiliation(s)
- Conrad J Fernandes
- Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Galen Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Jennifer R Eads
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA.
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24
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de Jorge Huerta L, Solares Fernández I, Sánchez-Moreno B, Males Maldonado D, de Ibarrola Andrés C, Díaz-Simón R. Sporadic, non-functional, gastrin-producing duodenal neuroendocrine tumors: A retrospective study of an infrequent disease. J Dig Dis 2022; 23:455-461. [PMID: 36168962 PMCID: PMC10099524 DOI: 10.1111/1751-2980.13129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 07/19/2022] [Accepted: 09/25/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Non-functioning gastrin-producing neuroendocrine neoplasms (NEN) of the duodenum are rare gastrointestinal tumors without a clinical syndrome due to gastrin production. Their incidence has significantly increased as an incidental finding during endoscopic studies. The aim of this study was to describe the characteristics and prognostic factors of this emergent and infrequent neoplasm. METHODS We performed a retrospective observational study based on the duodenal NENs samples with positive staining for gastrin at the Department of Pathology, University Hospital 12-de-Octubre (Madrid, Spain) between 2000 and 2017. Patients with clinically functional tumors ([Zollinger-Ellison syndrome] or gastrin >1000 pg/mL), with previously diagnosed multiple endocrine neoplasia (MEN) syndrome or synchronous neoplasia were excluded. Clinicopathological and therapeutic variables, follow-up, recurrence, and mortality data were collected. RESULTS In all, 21 patients were included. Most of the tumors were diagnosed incidentally as a single small polypoid lesion limited to mucosa/submucosa and with a low histological grade. Four (19.0%) patients presented with metastatic involvement at diagnosis (lymphatic and/or hepatic). These four patients also had a high or intermediate mitotic grade and infiltration further than submucosa. Local resection was applied in most cases as curative treatment. There were two cases of tumor recurrence and two tumor-related deaths with a 5-year disease-free survival of 81.0%. CONCLUSIONS The majority of these tumors were diagnosed at a localized stage and had a good prognosis with treatment. Nevertheless, given the potential metastatic risk, a close follow-up is necessary, especially in those with aggressive pathological factors such as deep infiltration or high histological grade.
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Affiliation(s)
- Lucía de Jorge Huerta
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - Isabel Solares Fernández
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - Beatriz Sánchez-Moreno
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - David Males Maldonado
- Department of Endocrinology and Metabolism, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - Carolina de Ibarrola Andrés
- Department of Anatomical Pathology, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - Raquel Díaz-Simón
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
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25
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Ehlken H, Younis F, Wolter S, Schrader J. Spannungsfeld endoskopische Resektionsverfahren bei GEP-NET // Endoscopic resection for GEP-NET. Zentralbl Chir 2022; 147:256-263. [PMID: 35705087 DOI: 10.1055/a-1829-7370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
ZusammenfassungNeuroendokrine Tumoren des Verdauungstraktes (GEP-NET) sind eine seltene Tumorentität, die häufig als Zufallsbefund diagnostiziert werden. Ein großer Teil dieser Zufallsdiagnosen wird im
Rahmen einer endoskopischen Untersuchung gestellt. Während die vollständige Entfernung des Tumors im Sinne einer kurativen chirurgischen Resektion nach onkologischen Kriterien das
Standardvorgehen für lokalisierte Tumorerkrankungen ist, kann bei kleinen Tumoren ohne Hinweis und Risiko für eine lymphogene Metastasierung eine endoskopische Abtragung in gleicher
Intention erfolgen. Während dies für Magen-, Duodenum- und Rektum-NET der Standard ist, sollten NET des Jejunums und Ileums aufgrund der hohen Metastasierungsrate trotz geringer Tumorgröße
regelhaft nicht endoskopisch angegangen werden. Die Grenze für eine endoskopische Resektion ergibt sich sowohl durch die technische Machbarkeit im Sinne des Erreichens einer R0-Resektion,
der erwarteten Komplikationen im Sinne von Blutung und Perforationen als auch durch das vermutete Risiko für eine lymphogene Metastasierung. Generell wird eine endoskopische Resektion bei
Befunden < 1 cm regelhaft empfohlen, da sowohl die gute technische Machbarkeit als auch das geringe Metastasierungsrisiko für eine endoskopische Resektion sprechen. Bei allen Befunden
über 2 cm Größe sind sowohl die technischen Erfolgsaussichten so niedrig als auch das Metastasierungsrisiko so hoch, dass in dieser Situation regelhaft ein chirurgisches Vorgehen erfolgen
sollte. Es bleibt somit ein Graubereich bei der Tumorgröße zwischen 1 und 2 cm, wo sowohl endoskopische, aber auch chirurgische Resektionsverfahren sinnvoll eingesetzt werden können.
Zunehmend kommen auch gemeinsame Eingriffe im Sinne eines endoskopisch-laparoskopischen Rendezvous-Verfahrens zum Einsatz – insbesondere im Duodenum bieten sich diese Eingriffe an, um eine
minimale Resektion mit größtmöglicher R0-Erfolgsrate und niedriger Perforationsrate zu erreichen.
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Affiliation(s)
- Hanno Ehlken
- Klinik und Poliklinik für interdisziplinäre Endoskopie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Fadi Younis
- Klinik und Poliklinik für interdisziplinäre Endoskopie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Stefan Wolter
- Klinik für Allgemein-, Viszeral und Thoraxchirurgie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
| | - Jörg Schrader
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
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26
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Borbath I, Pape UF, Deprez PH, Bartsch DK, Caplin M, Falconi M, Garcia-Carbonero R, Grozinsky-Glasberg S, Jensen RT, Arnold R, Ruszniewski P, Toumpanakis C, Valle JW, O Toole D. ENETS standardized (synoptic) reporting for endoscopy in neuroendocrine tumors. J Neuroendocrinol 2022; 34:e13105. [PMID: 35233848 DOI: 10.1111/jne.13105] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 01/27/2022] [Accepted: 02/05/2022] [Indexed: 02/06/2023]
Abstract
Despite efforts from various endoscopy societies, reporting in the field of endoscopy remains extremely heterogeneous. Harmonisation of clinical practice in endoscopy has been highlighted by application of many clinical practice guidelines and standards pertaining to the endoscopic procedures and reporting are underlined. The aim of the proposed "standardised reporting" is to (1) facilitate recognition of gastrointestinal neuroendocrine neoplasms (NEN) on initial endoscopy, (2) to enable interdisciplinary decision making for treatment by a multidisciplinary team, (3) to provide a basis for a standardised endoscopic follow-up which allows detection of recurrence or progression reliably, (4) to make endoscopic reports on NEN comparable between different units, and (5) to allow research collaboration between NEN centres in terms of consistency of their endoscopic data. The ultimate goal is to improve disease management, patient outcome and reduce the diagnostic burden on the side of the patient by ensuring the highest possible diagnostic accuracy and validity of endoscopic exams and possibly interventions.
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Affiliation(s)
- Ivan Borbath
- Department of Hepato-Gastroenterology, Cliniques universitaires Saint-Luc, Bruxelles, Belgium
| | - Ulrich-Frank Pape
- Department of Internal Medicine and Gastroenterology, Asklepios Klinik St. Georg, Asklepios Tumorzentrum Hamburg, Hamburg, Germany
- Department of Hepatology and Gastroenterology, Charité Campus Mitte, Charité University Medicine Berlin, Berlin, Germany
| | - Pierre H Deprez
- Department of Hepato-Gastroenterology, Cliniques universitaires Saint-Luc, Bruxelles, Belgium
| | - Detlef Klaus Bartsch
- Department of Visceral-, Thoracic- and Vascular Surgery at the Philipps-University Marburg, Marburg, Germany
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital and University College London, London, UK
| | - Massimo Falconi
- Department of Surgery, San Raffaele Hospital IRCCS, Università Vita-e-Salute, Milan, Italy
| | | | - Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Division of Medicine, Endocrinology & Metabolism Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Robert T Jensen
- Gastrointestinal Cell Biology Section, Digestive Disease Branch, National Institute of Health, Bethesda, Maryland, USA
| | - Rudolf Arnold
- Zentrum für Innere Medizin, Universitätsklinikum Marburg, Marburg, Germany
| | - Philippe Ruszniewski
- Department of Gastroenterology-Pancreatology, Beaujon Hospital and Université de Paris, Clichy, France
| | - C Toumpanakis
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital and University College London, London, UK
| | - Juan W Valle
- Department of Medical Oncology, University of Manchester/The Christie NHS Foundation Trust, Manchester, UK
| | - Dermot O Toole
- National Centre for Neuroendocrine Tumours, St Vincent's University Hospital and St James's Hospital and Trinity College Dublin, Dublin, Ireland
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27
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Kohno S. Diagnosis and Surgical Treatment of Gastroenteropancreatic Neuroendocrine Neoplasms: A Literature Review. CANCER DIAGNOSIS & PROGNOSIS 2022; 2:115-125. [PMID: 35399177 PMCID: PMC8962810 DOI: 10.21873/cdp.10085] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 01/31/2022] [Indexed: 06/14/2023]
Abstract
This review aimed to highlight the characteristics and surgical treatments of tumours, and answer questions regarding the assessment of gastrointestinal neuroendocrine neoplasms (NENs) and optimal therapy. NENs comprise tumours that can produce hormones and cause a secretory syndrome. The diagnostic method and accuracy differ depending on the site of occurrence; hence, the relevant scientific society has created NEN treatment guidelines for each organ. Gastroenteric pancreatic (GEP) NENs have been unified and classified together according to the 2019 World Health Organization classification. Treatment is based on complete tumour resection, and when metastatic or primary lesions cannot be completely resected, lesions and symptoms are treated. Except for surgery for NENs, chemotherapy, molecularly targeted drugs, transarterial chemoembolization, etc., have also been confirmed as treatments. GEP NEN treatment methods will continue to advance and change because of surgery and other advances in treatment and diagnostic methods.
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Affiliation(s)
- Shuzo Kohno
- Department of Surgery, The Jikei University Katsushika Medical Center, Tokyo, Japan
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28
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Tran CG, Sherman SK, Suraju MO, Nayyar A, Gerke H, El Abiad RG, Chandrasekharan C, Ear PH, O’Dorisio TM, Dillon JS, Bellizzi AM, Howe JR. Management of Duodenal Neuroendocrine Tumors: Surgical versus Endoscopic Mucosal Resection. Ann Surg Oncol 2022; 29:75-84. [PMID: 34515889 PMCID: PMC8688294 DOI: 10.1245/s10434-021-10774-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 08/22/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Management of duodenal neuroendocrine tumors (DNETs) is not standardized, with smaller lesions (< 1-2 cm) generally treated by endoscopic mucosal resection (EMR) and larger DNETs by surgical resection (SR). This study reviewed how patients were selected for treatment and compared outcomes. PATIENTS AND METHODS Patients with DNETs undergoing resection were identified through institutional databases, and clinicopathologic data recorded. χ2 and Wilcoxon tests compared variables. Survival was determined by Kaplan-Meier, and Cox regression tested association with survival. RESULTS Among 104 patients, 64 underwent EMR and 40 had SR. Patients selected for SR had larger tumor size, younger age, and higher T, N, and M stage. There was no difference in progression-free (PFS) or overall survival (OS) between SR and EMR. In 1-2 cm DNETs, there was no difference in PFS between SR and EMR [median not reached (NR), P = 0.1]; however, longer OS was seen in SR (median NR versus 112 months, P = 0.03). In 1-2 cm DNETs, SR patients were more likely to be node-positive and younger. After adjustment for age, resection method did not correlate with survival. Comparison of surgically resected DNETs versus jejunoileal NETs revealed longer PFS (median NR versus 73 months, P < 0.001) and OS (median NR versus 119 months, P = 0.004) DISCUSSION: In 1-2 cm DNETs, there was no difference in survival between EMR and SR after adjustment for age. Recurrences could be salvaged, suggesting that EMR is a reasonable strategy. Compared with jejunoileal NETs, DNETs treated by SR had improved PFS and OS.
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Affiliation(s)
- Catherine G. Tran
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Scott K. Sherman
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Mohammed O. Suraju
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Apoorve Nayyar
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Henning Gerke
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Rami G. El Abiad
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
| | | | - Po Hien Ear
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Thomas M. O’Dorisio
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Joseph S. Dillon
- Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA
| | - Andrew M. Bellizzi
- Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA
| | - James R. Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
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29
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Matsueda K, Kanesaka T, Kitamura M, Shichijo S, Maekawa A, Yamamoto S, Takeuchi Y, Higashino K, Uedo N, Michida T, Honma K, Miyashiro I, Ishihara R. Favorable long-term outcomes of endoscopic resection for nonampullary duodenal neuroendocrine tumor. J Gastroenterol Hepatol 2021; 36:3329-3336. [PMID: 34142385 DOI: 10.1111/jgh.15586] [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: 04/13/2021] [Revised: 05/30/2021] [Accepted: 06/15/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM The long-term outcomes of endoscopic resection for nonampullary duodenal neuroendocrine tumors are limited. We aimed to clarify it. METHODS Consecutive patients with nonampullary duodenal neuroendocrine tumors endoscopically treated at our institute between January 2005 and June 2020 were included in this retrospective study. En bloc and R0 resection rates and adverse events were evaluated as short-term outcomes of endoscopic resection. The 5-year overall and recurrence-free survival rates of patients after endoscopic resection were calculated as long-term outcomes. RESULTS Of 34 patients with 34 lesions, 33 patients (97%) underwent endoscopic mucosal resection, and one (3%) underwent endoscopic submucosal dissection. En bloc resection was achieved in 33 lesions (97%). R0 resection was achieved in 20 lesions (59%). The median tumor size was 6 mm (range: 3-13). Thirty-one lesions (91%) and three lesions (9%) were classified as G1 and G2, respectively. Lymphovascular invasion was observed in six lesions (18%). Intraprocedural perforation occurred in four patients (12%) who were conservatively treated with endoscopic closure. All 34 patients were followed up without additional treatment after endoscopic resection, and no recurrence or metastasis developed during the median follow-up period of 47.9 months (range: 9.0-187.1). The 5-year overall survival and recurrence-free survival rates were 87.1% and 100%, respectively. CONCLUSIONS Endoscopic resection provided a favorable long-term prognosis for patients with nonampullary duodenal neuroendocrine tumors without lymph node metastasis.
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Affiliation(s)
- Katsunori Matsueda
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Takashi Kanesaka
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Masanori Kitamura
- Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
| | - Satoki Shichijo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Akira Maekawa
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Sachiko Yamamoto
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Yoji Takeuchi
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Koji Higashino
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Tomoki Michida
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Keiichiro Honma
- Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan
| | - Isao Miyashiro
- Cancer Control Center, Osaka International Cancer Institute, Osaka, Japan
| | - Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
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Zenovia S, Neculae E, Trifan AV, Dimache M, Fotea V, Sîngeap AM. Duodenal large-cell neuroendocrine carcinoma as unusual cause of acute pancreatitis. Arch Clin Cases 2021; 7:15-21. [PMID: 34754922 PMCID: PMC8565687 DOI: 10.22551/2020.26.0701.10167] [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] [Indexed: 11/25/2022] Open
Abstract
Early identification of acute pancreatitis etiology is essential for choosing the best therapeutic management. The main causes are cholelithiasis and alcohol consumption. Tumors that obstruct the main pancreatic duct are uncommon causes of acute pancreatitis. Duodenal neuroendocrine tumors are rare entities and may be exceptional causes of acute pancreatitis. A 57-year-old male, with associated severe cardiovascular pathology, was admitted with clinical and biological picture of acute pancreatitis. Biliary and alcoholic causes were excluded. Abdominal contrast-enhanced computed tomography scan identified circumferential wall thickening of the second segment of the duodenum with peri-ampullary and papillary nodular non-homogenous contrast enhancement aspect. Upper gastrointestinal endoscopy described irregular hypertrophic duodenal mucosal folds and biopsies were performed. The histopathological diagnosis after immunohistochemistry tests was duodenal large-cell neuroendocrine carcinoma. The patient was referred to the oncology clinic and palliative treatment was initiated. The evolution was marked by additional complications due to the tumor evolution – upper gastrointestinal bleeding and obstructive jaundice, conservatory treated and, respectively, by interventional radiology technique. This case illustrates that, although often obvious, etiological diagnosis approach of acute pancreatitis can be sometimes challenging. Tumor cause is infrequent and requires thorough work-up, as the treatment is different. Although extremely rare and sometimes with mild clinical presentation, duodenal neuroendocrine carcinomas may have dramatic onset and evolution, involving extensive therapeutic resources.
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Affiliation(s)
- Sebastian Zenovia
- "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Ecaterina Neculae
- "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania
| | - Anca Victorița Trifan
- "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania.,Gastroenterology and Hepatology Clinic, "Sf. Spiridon" Emergency Clinical Hospital, Iasi, Romania
| | - Mihaela Dimache
- "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania.,Gastroenterology and Hepatology Clinic, "Sf. Spiridon" Emergency Clinical Hospital, Iasi, Romania
| | - Vasile Fotea
- "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania.,Radiology Department, "Sf. Spiridon" Emergency Clinical Hospital, Iasi, Romania
| | - Ana-Maria Sîngeap
- "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania.,Gastroenterology and Hepatology Clinic, "Sf. Spiridon" Emergency Clinical Hospital, Iasi, Romania
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31
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Yozgat A, Kekilli M, Altay M. Time to give up traditional methods for the management of gastrointestinal neuroendocrine tumours. World J Clin Cases 2021; 9:8627-8646. [PMID: 34734042 PMCID: PMC8546836 DOI: 10.12998/wjcc.v9.i29.8627] [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: 02/20/2021] [Revised: 05/19/2021] [Accepted: 08/24/2021] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) are a rare and heterogeneous disease group and constitute 0.5% of all malignancies. The annual incidence of NETs is increasing worldwide. The reason for the increase in the incidence of NETs is the detection of benign lesions, incidental detection due to the highest use of endoscopic and imaging procedures, and higher recognition rates of pathologists. There have been exciting developments regarding NET biology in recent years. Among these, first of all, somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis, hormone secretion, and proliferation. Subsequently, activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism. Finally, the importance of proangiogenic factors (platelet-derived growth factor, vascular endothelial growth factor, fibroblastic growth factor, angiopoietin, and semaphorins) in the progression of NET has been determined. Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.
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Affiliation(s)
- Ahmet Yozgat
- Department of Gastroenterology, Ufuk University, Ankara, 06510, Turkey
| | - Murat Kekilli
- Department of Gastroenterology, Gazi University, Ankara 06560, Turkey
| | - Mustafa Altay
- Department of Endocrinology and Metabolism, University of Health Sciences Turkey, Keçiören Health Administration and Research Center, Ankara 06190, Turkey
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Rossi RE, Milanetto AC, Andreasi V, Campana D, Coppa J, Nappo G, Rinzivillo M, Invernizzi P, Modica R, David A, Partelli S, Lamberti G, Mazzaferro V, Zerbi A, Panzuto F, Pasquali C, Falconi M, Massironi S. Risk of preoperative understaging of duodenal neuroendocrine neoplasms: a plea for caution in the treatment strategy. J Endocrinol Invest 2021; 44:2227-2234. [PMID: 33651317 DOI: 10.1007/s40618-021-01528-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 02/04/2021] [Indexed: 02/05/2023]
Abstract
PURPOSE Pretreatment staging is the milestone for planning either surgical or endoscopic treatment in duodenal neuroendocrine neoplasms (dNENs). Herein, a series of surgically treated dNEN patients was evaluated to assess the concordance between the pre- and postsurgical staging. METHODS Retrospective analysis of patients with a histologically confirmed diagnosis of dNENs, who underwent surgical resection observed at eight Italian tertiary referral centers. The presurgical TNM stage, based on the radiological and functional imaging, was compared with the pathological TNM stage, after surgery. RESULTS From 2000 to 2019, 109 patients were included. Sixty-six patients had G1, 26 a G2, 7 a G3 dNEN (Ki-67 not available in 10 patients). In 46/109 patients (42%) there was disagreement between the pre- and postsurgical staging, being it understaged in 42 patients (38%), overstaged in 4 (3%). As regards understaging, in 25 patients (22.9%), metastatic loco-regional nodes (N) resulted undetected at both radiological and functional imaging. Understaging due to the presence of distal micrometastases (M) was observed in 2 cases (1.8%). Underestimation of tumor extent (T) was observed in 12 patients (11%); in three cases the tumor was understaged both in T and N extent. CONCLUSIONS Conventional imaging has a poor detection rate for loco-regional nodes and micrometastases in the presurgical setting of the dNENs. These results represent important advice when local conservative approaches, such as endoscopy or local surgical excision are considered and it represents a strong recommendation to include endoscopic ultrasound in the preoperative tools for a more accurate local staging.
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Affiliation(s)
- R E Rossi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
- HBP Surgery, Hepatology and Liver Transplantation Unit, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan, Italy.
| | - A C Milanetto
- Pancreatic and Endocrine Digestive Surgical Unit, Department of Surgery, Oncology and Gastroenterology, Università degli Studi di Padova, Padua, Italy
| | - V Andreasi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy
| | - D Campana
- Department of Experimental, Diagnostic and Specialty Medicine, ENETS Center of Excellence, Bologna University, St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - J Coppa
- HBP Surgery, Hepatology and Liver Transplantation Unit, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan, Italy
| | - G Nappo
- Pancreatic Surgery, Humanitas Clinical, and Research Center-IRCCS, ENETS Center of Excellence, Humanitas University, Milan, Rozzano, Italy
| | - M Rinzivillo
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - P Invernizzi
- Division of Gastroenterology, San Gerardo Hospital, Bicocca School of Medicine, University of Milano, Monza, Italy
| | - R Modica
- Division of Endocrinology, Department of Clinical Medicine and Surgery, ENETS Center of Excellence, University "Federico II" of Naples, Naples, Italy
| | - A David
- Pancreatic and Endocrine Digestive Surgical Unit, Department of Surgery, Oncology and Gastroenterology, Università degli Studi di Padova, Padua, Italy
| | - S Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy
| | - G Lamberti
- Department of Experimental, Diagnostic and Specialty Medicine, ENETS Center of Excellence, Bologna University, St. Orsola-Malpighi University Hospital, Bologna, Italy
| | - V Mazzaferro
- HBP Surgery, Hepatology and Liver Transplantation Unit, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
| | - A Zerbi
- Pancreatic Surgery, Humanitas Clinical, and Research Center-IRCCS, ENETS Center of Excellence, Humanitas University, Milan, Rozzano, Italy
| | - F Panzuto
- Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - C Pasquali
- Pancreatic and Endocrine Digestive Surgical Unit, Department of Surgery, Oncology and Gastroenterology, Università degli Studi di Padova, Padua, Italy
| | - M Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Center, ENETS Center of Excellence, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy
| | - S Massironi
- Division of Gastroenterology, San Gerardo Hospital, Bicocca School of Medicine, University of Milano, Monza, Italy
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Carvão J, Dinis-Ribeiro M, Pimentel-Nunes P, Libânio D. Neuroendocrine Tumors of the Gastrointestinal Tract: A Focused Review and Practical Approach for Gastroenterologists. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2021; 28:336-348. [PMID: 34604465 PMCID: PMC8443956 DOI: 10.1159/000512089] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 10/01/2020] [Indexed: 02/05/2023]
Abstract
Neuroendocrine tumors (NETs) are rare tumors derived from the neuroendocrine cell system, and more commonly found in the gastrointestinal (GI) tract. Over the last decades, the incidence of GI-NETs has been steadily increasing, partly due to the expanding indications for endoscopy. Most patients with NETs are asymptomatic, and their NETs are noticed during screening examinations; thus, endoscopists are on the frontline of the diagnosis of GI-NETs. Since GI-NETs are less frequent than other malignancies, the natural history, diagnosis, and management of these tumors may not be fully understood. In this review, we aim to update the endoscopist on key clinical features and management of patients with gastric, duodenal, and rectal NETs.
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Affiliation(s)
- Joana Carvão
- Gastroenterology Department, Hospital Central do Funchal, Funchal, Portugal
| | - Mário Dinis-Ribeiro
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Pedro Pimentel-Nunes
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
- Surgery and Physiology Department, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Diogo Libânio
- Gastroenterology Department, Instituto Português de Oncologia do Porto, Porto, Portugal
- MEDCIDS − Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Porto, Portugal
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Folkestad O, Wasmuth HH, Mjønes P, Fougner R, Hauso Ø, Fossmark R. Survival and Disease Recurrence in Patients with Duodenal Neuroendocrine Tumours-A Single Centre Cohort. Cancers (Basel) 2021; 13:cancers13163985. [PMID: 34439140 PMCID: PMC8391208 DOI: 10.3390/cancers13163985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/02/2021] [Accepted: 08/04/2021] [Indexed: 12/02/2022] Open
Abstract
Simple Summary Neuroendocrine tumours of the upper part of the small intestine are rare. They are slow growing but may spread to lymph nodes or other organs already when the tumours are small. Such tumours may be treated by endoscopic removal or by an operation. In the current study we present the treatment results of 32 patients with this rare tumour. We found that the long-term survival was long, and patients more often died from other diseases. The survival was associated with the growth rate of the tumours and whether all the tumour tissue could be removed. Endoscopic removal was sufficient for smaller tumours <10 mm, whereas a high proportion of tumours 10–20 mm have lymph node metastases that must be removed by an operation to make patients tumour free. None of the tumours that were perceived as cured after removal recurred after an average follow-up time of 4.8 years. Abstract Background: Duodenal neuroendocrine tumours (D-NETs) are rare but increasingly diagnosed. This study aimed to assess the overall survival and recurrence rate among patients treated for D-NETs. Methods: Patients with D-NETs were retrospectively reviewed with a median follow-up time of 4.8 years (range 0.0–17.2 years). Results: A total of 32 patients with median age 68.0 years were identified. Fifteen patients underwent surgery while ten patients underwent endoscopic treatment. Mean estimated overall survival for the entire population was 12.1 years (95% CI 9.5–14.7 years), while 5-year overall survival was 81.3%. Tumour grade G1 was associated with longer mean estimated survival compared to G2 tumours (13.2 years versus 4.4 years, p = 0.010). None of the 23 patients who underwent presumed radical endoscopic or surgical resection had disease recurrence during follow-up. Tumours <10 mm could be treated endoscopically whereas a high proportion of patients with tumours 10–20 mm should be considered for surgery. Conclusion: Patients with D-NETs had long overall survival, and mortality was more influenced by other diseases. Both endoscopic and surgical resections were effective as no recurrences were diagnosed during follow-up.
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Affiliation(s)
- Oddry Folkestad
- Department of Gastrointestinal Surgery, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway;
- Department of Gastrointestinal Surgery, Vestfold Hospital, 3103 Tønsberg, Norway
| | - Hans H. Wasmuth
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
| | - Patricia Mjønes
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Pathology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Reidun Fougner
- Department of Radiology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway;
| | - Øyvind Hauso
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Gastroenterology and Hepatology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway; (H.H.W.); (P.M.); (Ø.H.)
- Department of Gastroenterology and Hepatology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Correspondence: ; Tel.: +47-7292-5164
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Sakaray Y, Abuji K, Chatterjee D, Irrinki S. Giant retroperitoneal lymph node-an uncommon presentation of duodenal neuroendocrine tumour. BMJ Case Rep 2021; 14:14/7/e243048. [PMID: 34290018 DOI: 10.1136/bcr-2021-243048] [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: 11/04/2022] Open
Abstract
Primary retroperitoneal neuroendocrine tumours (NETs) are extremely rare, and many a times, these are metastatic lesions with known or unknown primary location, most commonly arising from the stomach, duodenum, small intestine and rectum. NETs arising from the duodenum are more commonly seen in the first part of the duodenum followed by the second part. The incidence is increasing because of easy accessibility to endoscopies and cross-sectional imaging. In NETs, lymph node (LN) metastasis occurs commonly when the tumour size is more than 2 cm. In contrast, LN metastasis occurs even with subcentimetric lesions, especially the ampullary variant of NETs. A patient presented to us with mild abdominal pain and found to have retroduodenal mass. On evaluation found to be a metastatic LN deposit of NET with the primary arising from the first part and supra-ampullary part of duodenum.
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Affiliation(s)
- Yashwant Sakaray
- General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kishore Abuji
- General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Debajyoti Chatterjee
- Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Santhosh Irrinki
- General Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Wang R, Mohapatra S, Jovani M, Akshintala VS, Kamal A, Brewer OG, Kumbhari V, Shin EJ, Canto MI, Khashab MA, Singh VK, Lennon AM, Kalloo AN, Ngamruengphong S. Risk factors for lymph node metastasis and survival of patients with nonampullary duodenal carcinoid tumors treated with endoscopic therapy versus surgical resection: analysis of the Surveillance, Epidemiology, and End Results program. Gastrointest Endosc 2021; 93:1384-1392. [PMID: 33347833 DOI: 10.1016/j.gie.2020.12.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Accepted: 12/03/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Endoscopic therapy (ET) has been used to treat nonampullary duodenal neuroendocrine tumors (NAD-NETs) ≤10 mm in size, but data on long-term outcomes are limited. In addition, management of 11- to 19-mm NAD-NETs is not well defined because of variable estimates of risk of metastasis. We aimed to determine the prevalence and risk factors of metastasis of NAD-NETs ≤19 mm and evaluate the long-term survival of patients after ET as compared with radical surgery. METHODS The Surveillance Epidemiology and End Result database was used to identify 1243 patients with T1-2 histologically confirmed NAD-NETs ≤19 mm in size. Cancer-specific survival (CSS) and overall survival (OS) were calculated. RESULTS Overall, 4.8% of cases had metastasis at the time of diagnosis, with lower prevalence in ≤10-mm lesions (3.1%) versus 11- to 19-mm lesions (11.7%, P < .001). The risk factors for metastases included invasion to the muscularis propria (odds ratio, 25.95; 95% confidence interval, 9.01-76.70), age <65 years (odds ratio, 1.93), submucosal involvement (odds ratio, 3.1), and 11 to 19 mm in size (vs ≤10 mm). In patients with well- to moderately differentiated T1-2N0M0 NAD-NETs ≤19 mm confined to the mucosa/submucosa who underwent ET or surgery, the 5-year CSS was 100%. The 5-year OS was similar between the ≤10-mm and 11- to 19-mm groups (86.6% vs 91.0%, P = .31) and the ET and surgery groups (87.4% vs 87.5%, P = .823). CONCLUSIONS In NAD-NETs, invasion to the muscularis propria is the strongest risk factor for metastasis. In the absence of metastasis, in lesions with well/moderate differentiation and without muscle invasion, ET is adequate for NAD-NETs ≤10 mm and is a viable option for 11- to 19-mm lesions.
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Affiliation(s)
- Rui Wang
- Gastroenterology Department, West China Hospital of Sichuan University, Chengdu, Sichuan, China; Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Sonmoon Mohapatra
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Manol Jovani
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Venkata S Akshintala
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Ayesha Kamal
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Olaya Gutierrez Brewer
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Vivek Kumbhari
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Eun Ji Shin
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Marcia I Canto
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Mouen A Khashab
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Vikesh K Singh
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Anne Marie Lennon
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Anthony Nicholas Kalloo
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Saowanee Ngamruengphong
- Department of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
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Exarchou K, Moore AR, Smart HL, Duckworth CA, Howes N, Pritchard DM. A "Watch and Wait" Strategy Involving Regular Endoscopic Surveillance Is Safe for Many Patients with Small, Sporadic, Grade 1, Non-Ampullary, Non-Functioning Duodenal Neuroendocrine Tumours. Neuroendocrinology 2021; 111:764-774. [PMID: 32937631 DOI: 10.1159/000511613] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 09/09/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Duodenal neuroendocrine tumours (d-NETs) are rare but are increasing in incidence. Current ENETS guidelines advocate resection of all localized d-NETs. However, "watch and wait" may be appropriate for some localized, small, grade 1, non-functioning, non-ampullary d-NETs. We evaluated whether patients with such d-NETs who chose "watch and wait" involving regular endoscopic surveillance had equivalent disease-related outcomes to patients undergoing endoscopic or surgical resection. METHODS Retrospective review of patients with histologically confirmed d-NETs at Liverpool ENETS Centre of Excellence 2007-2020. RESULTS Sixty-nine patients were diagnosed with d-NET of which 50 were sporadic, non-functioning, non-ampullary tumours. Patient treatment groups were similar in terms of age, gender, and tumour location and grade, but unsurprisingly, larger tumours (median diameter 17 mm [p < 0.0001]) were found in the surgically treated group. Five patients underwent surgical resection with no evidence of tumour recurrence or disease-related death. Twelve patients underwent endoscopic resection (ER), with 1 local recurrence detected during follow-up. Thirty patients (28 with d-NETs ≤10 mm) underwent "watch and wait" with resection only if tumours increased in size. The d-NETs in 28/30 patients remained stable or decreased in size over a median 27 months (IQR: 15-48, R: 3-98). In 7 patients, the d-NET was completely removed by avulsion during diagnostic biopsy and was not seen at subsequent endoscopies. Only 2 patients showed increased d-NET size during surveillance, of whom only one was fit for ER. No NET-related deaths were documented during follow-up. CONCLUSIONS All of the localized, ≤10 mm, grade 1, non-functioning, non-ampullary d-NETs in this cohort behaved indolently with very low risks of progression and no tumour-related deaths. "Watch and wait," therefore, appears to be a safe alternative management strategy for selected d-NETs.
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Affiliation(s)
- Klaire Exarchou
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
- Department of Upper Gastrointestinal Surgery, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
| | - Andrew R Moore
- Department of Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
| | - Howard L Smart
- Department of Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
| | - Carrie A Duckworth
- Department of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Nathan Howes
- Department of Upper Gastrointestinal Surgery, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom
| | - D Mark Pritchard
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom,
- Department of Gastroenterology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom,
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Zhou YJ, Wang QW, Zhang QW, Chen JN, Wang XY, Gao YJ, Li XB. Patterns of Lymph Node Metastasis in Patients With T1/T2 Gastroduodenal Neuroendocrine Neoplasms: Implications for Endoscopic Treatment. Front Endocrinol (Lausanne) 2021; 12:658392. [PMID: 34122337 PMCID: PMC8194267 DOI: 10.3389/fendo.2021.658392] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 05/06/2021] [Indexed: 12/20/2022] Open
Abstract
Guidelines have differed in their opinion regarding the indications for endoscopic resection of gastric-neuroendocrine neoplasms (g-NENs) and duodenal-NENs (d-NENs). We examined the association between size and lymph node metastasis (LNM) to identify candidates most suitable for endoscopic resection. We identified 706 patients with T1/T2 g-NENs and 621 patients with T1/T2 d-NENs from the SEER database. The prevalence of LNM and risk factors associated with LNM were analyzed. LNM was present in 8.1% of patients with gastroduodenal neuroendocrine tumors (NETs) and 31.6% of patients with neuroendocrine carcinomas (NECs). Multivariate logistic regression indicated that tumor size >10mm, greater invasion depth, and poor differentiation were independently associated with LNM. In addition, the percentage of g-NETs invading submucosa with LNM increased with tumor size (≤10 mm,3.9%;11-20 mm,8.6%;>20 mm,16.1%). However, in contrast to the low LNM risk in patients with small g-NETs (≤10 mm), we found that LNM rate exceeded 5% even for patients with small submucosal-infiltrating d-NETs. Among patients with nodal-negative g-NETs, the cause specific survival (CSS) was similar for those who received surgical resection and endoscopic resection. Among patients with d-NETs, the CSS was better for those who received endoscopic resection. In conclusion, patients with d-NETs had a higher probability of LNM than those with g-NETs. Endoscopic resection can be utilized for curative treatment of submucosa-infiltrating g-NETs and intramucosal d-NETs when the size is 10 mm or less. These results reinforce the need to search for LNM in lesions that are larger than 10 mm.
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Gay-Chevallier S, de Mestier L, Perinel J, Forestier J, Hervieu V, Ruszniewski P, Millot I, Valette PJ, Pioche M, Lombard-Bohas C, Subtil F, Adham M, Walter T. Management and Prognosis of Localized Duodenal Neuroendocrine Neoplasms. Neuroendocrinology 2021; 111:718-727. [PMID: 32335556 DOI: 10.1159/000508102] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Accepted: 04/21/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The characteristics, prognostic factors, and management of duodenal neuroendocrine neoplasms (dNEN) are ill-defined, given their rarity. Whether nonsurgical management might be appropriate for patients with nonmetastatic dNEN and a good prognosis, as is the case for pancreatic NEN (pNEN), is unknown. We aimed to describe the management and prognosis of nonmetastatic dNEN patients. METHODS All consecutive patients with nonmetastatic dNEN managed between 1981 and 2018 in 2 expert centers were included. Recurrence-free survival (RFS) and factors associated with recurrence were estimated. RESULTS A total of 145 patients with dNEN were included. Twenty-eight patients with sporadic, nonfunctioning, small (median 7 mm) dNEN underwent endoscopic resection, with a 5-year RFS rate of 89.4%. Local recurrence occurred in 2 patients, who underwent surgery with no new events. The 5-year RFS rate was 87.9% in patients who underwent surgery. Upon univariate analysis, age, size, Ki67 index, and lymph node involvement (LN+) were significantly associated with worse RFS for all dNEN treated (endoscopy/surgery); multivariate analysis found that age, size, and LN+ were associated with worse RFS. CONCLUSION Selected nonmetastatic dNEN had a favorable outcome, and a less invasive therapeutic strategy appeared more suitable than oncological surgery.
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Affiliation(s)
- Servane Gay-Chevallier
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service de Gastroentérologie et d'Oncologie Médicale, Lyon, France
| | - Louis de Mestier
- Service de Gastroentérologie et Pancréatologie, Hôpital Beaujon, Université de Paris, Clichy, France
| | - Julie Perinel
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service de Chirurgie Digestive, Lyon, France
- Université Lyon 1, Université de Lyon, Lyon, France
| | - Julien Forestier
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service de Gastroentérologie et d'Oncologie Médicale, Lyon, France
| | - Valérie Hervieu
- Université Lyon 1, Université de Lyon, Lyon, France
- Hospices Civils de Lyon, Service de Pathologie Multisite, Site EST, Centre de Biologie et de Pathologie Est, Bron, France
| | - Philippe Ruszniewski
- Service de Gastroentérologie et Pancréatologie, Hôpital Beaujon, Université de Paris, Clichy, France
| | - Ingrid Millot
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service d'anesthésie-Réanimation, Lyon, France
| | - Pierre-Jean Valette
- Université Lyon 1, Université de Lyon, Lyon, France
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service de Radiologie, Lyon, France
| | - Mathieu Pioche
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service de Gastroentérologie et d'Oncologie Médicale, Lyon, France
- Université Lyon 1, Université de Lyon, Lyon, France
| | - Catherine Lombard-Bohas
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service de Gastroentérologie et d'Oncologie Médicale, Lyon, France
| | - Fabien Subtil
- Université Lyon 1, Université de Lyon, Lyon, France
- Hospices Civils de Lyon, Service de Biostatistiques, Lyon, France
- CNRS, Laboratoire de Biométrie et Biologie Évolutive UMR 5558, Villeurbanne, France
| | - Mustapha Adham
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service de Chirurgie Digestive, Lyon, France
- Université Lyon 1, Université de Lyon, Lyon, France
| | - Thomas Walter
- Hospices Civils de Lyon, Hôpital Édouard Herriot, Service de Gastroentérologie et d'Oncologie Médicale, Lyon, France,
- Université Lyon 1, Université de Lyon, Lyon, France,
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Zhang YQ, Wen JX, Luo RK, Yuan HX, Wang WP. Imaging and Contrast-enhanced Ultrasound features of duodenal neuroendocrine tumor: A case report. Clin Hemorheol Microcirc 2020; 76:27-32. [PMID: 32538825 DOI: 10.3233/ch-200816] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Duodenal neuroendocrine tumors are rare neoplasms arising from endocrine cells. Here we present a case of 32-year-old woman with Duodenal neuroendocrine tumors, report the imaging and contrast-enhanced Ultrasound (CEUS) features and review previous literatures of neuroendocrine tumors, which may be valuable for the differential diagnosis of duodenal neoplasms.
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Affiliation(s)
- Yan-Qun Zhang
- Department of Ultrasound, Xiamen Branch, Zhongshan Hospital of Fudan University, Xiamen, Fujian Province, China.,Department of Ultrasound, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Jie-Xian Wen
- Department of Ultrasound, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Rong-Kui Luo
- Department of Pathology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Hai-Xia Yuan
- Department of Ultrasound, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Wen-Ping Wang
- Department of Ultrasound, Zhongshan Hospital of Fudan University, Shanghai, China
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Gangliocytic Paraganglioma of Ampulla Masquerading as a Neuroendocrine Tumor. J Gastrointest Cancer 2020; 52:776-779. [PMID: 32895898 DOI: 10.1007/s12029-020-00507-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Costa RDD, Kemp R, Santos JSD, Costa DAPD, Ardengh JC, Ribas-Filho JM, Ribas CAPM. THE ROLE OF CONVENTIONAL ECHOENDOSCOPY (EUS) IN THERAPEUTIC DECISIONS IN PATIENTS WITH NEUROENDOCRINE GASTROINTESTINAL TUMORS. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2020; 33:e1512. [PMID: 32844878 PMCID: PMC7448866 DOI: 10.1590/0102-672020190001e1512] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 04/23/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Gastrointestinal neuroendocrine tumors are rare, usually presented as subepithelial or polypoid tumors. Accurate diagnosis and indication of the type of resection are still challenging. AIM To determine the effectiveness of echoendoscopy in determining the depth of the lesions (T) identified by endoscopy in order to evaluate surgical and/or endoscopic indication, and to evaluate the results of endoscopic removal in the medium term. METHODS Twenty-seven patients were included, all of whom underwent echoendoscopy for TN tumor staging and the evaluation of possible endoscopic resection. The parameters were: lesion size, origin layer, depth of involvement and identified perilesional adenopathies. The inclusion criteria for endoscopic resection were: 1) high surgical risk; 2) those with NET <2 cm; 3) absence of impairment of the muscle itself; and 4) absence of perilesional adenopathies in echoendoscopy and in others without distant metastases. Exclusion criteria were TNE> 2 cm; those with infiltration of the muscle itself; with perilesional adenopathies and distant metastases. The techniques used were: resection with polypectomy loop; mucosectomy with saline injection; and mucosectomy after ligation with an elastic band. The anatomopathological study of the specimens included evaluation of the margins and immunohistochemistry (chromogranin, synaptophysin and Ki 67) to characterize the tumor. Follow-up was done at 1, 6 and 12 months. RESULTS Resections with polypectomy loop were performed in 15 patients; mucosectomy in five; mucosectomy and ligation with elastic band in three and the remaining four were referred for surgery. The anatomopathological specimens and immunohistochemical analyzes showed positive chromogranin and synaptophysin, while Ki 67 was less than 5% among all cases. The medium-term follow-up revealed three recurrences. The average size of tumors in the stomach was 7.6 mm and in the duodenum 7.2 mm. Well-demarcated, hypoechoic, homogeneous lesions occurred in 75%; mucous layer in 80%; and the deep and submucosal mucosa in 70%. CONCLUSIONS Echoendoscopy proved to be a good method for the study of subepithelial lesions, being able to identify the layer affected by the neoplasm, degree of invasion, echogenicity, heterogeneity, size of the lesion and perilesional lymph node involvement and better indicate the treatment option.
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Affiliation(s)
- Rodrigo Dias da Costa
- Medical Research Institute, University Evangelical Hospital of Curitiba, Evangelical Faculty of Paraná, Curitiba, PR, Brazil
| | - Rafael Kemp
- Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
| | - José Sebastião Dos Santos
- Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil
| | | | - José Celso Ardengh
- Medical Research Institute, University Evangelical Hospital of Curitiba, Evangelical Faculty of Paraná, Curitiba, PR, Brazil
| | - Jurandir Marcondes Ribas-Filho
- Medical Research Institute, University Evangelical Hospital of Curitiba, Evangelical Faculty of Paraná, Curitiba, PR, Brazil
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Ahmed M. Gastrointestinal neuroendocrine tumors in 2020. World J Gastrointest Oncol 2020; 12:791-807. [PMID: 32879660 PMCID: PMC7443843 DOI: 10.4251/wjgo.v12.i8.791] [Citation(s) in RCA: 130] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/26/2020] [Accepted: 07/18/2020] [Indexed: 02/05/2023] Open
Abstract
Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological, biological, and clinical characteristics that have increased in incidence and prevalence within the last few decades. They contain chromogranin A, synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor. Ki-67 index and mitotic index correlate with cellular proliferation. Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors. Most of the gastrointestinal neuroendocrine tumors are non-functional. World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm. Gastric neuroendocrine tumors arise from enterochromaffin like cells. They are classified into 4 types. Only type I and type II are gastrin dependent. Small intestinal neuroendocrine tumor is the most common small bowel malignancy. More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve. Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs. Duodenal and jejuno-ileal neuroendocrine tumors are distinct biologically and clinically. Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver. Appendiceal neuroendocrine tumors are generally detected after appendectomy. Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis. Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000. Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy, endoscopic ultrasound, serology of biomarkers, imaging studies and functional somatostatin scans. Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.
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Affiliation(s)
- Monjur Ahmed
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Thomas Jefferson University, Philadelphia, PA 19107, United States
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Kachare SD, Liner KR, Vohra NA, Zervos EE, Fitzgerald TL. A Modified Duodenal Neuroendocrine Tumor Staging Schema Better Defines the Risk of Lymph Node Metastasis and Disease-free Survival. Am Surg 2020. [DOI: 10.1177/000313481408000836] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Duodenal neuroendocrine tumors are rare but increasing in incidence and optimal management is hindered by lack of duodenum-specific staging. Duodenal carcinoids were identified in the Surveillance, Epidemiology and End Results tumor registry. Depth of invasion was defined as limited to lamina propria (LP), invading muscularis propria (MP), through muscularis propria (TMP), and through serosa (S). Nine hundred forty-nine patients were identified with majorities being male (57%), white (70%), and node-negative (87%). Tumor size (cm) was less than 1, 47 per cent; 1 to 2, 35 per cent; and greater than 2, 8 per cent with 76 per cent LP. Lymph node (LN) involvement was associated with age, depth of invasion (LP 4%, MP 28%, TMP 54%, and S 57%) and size (less than 1 cm, 3%; 1 to 2 cm, 13%; and greater than 2 cm, 40%). Using the current T staging, LN involvement was: T1 (LP) 2 per cent, T2 (MP or greater than 1 cm) 13 per cent, T3 (TMP) 54 per cent, and T4 (S) 57 per cent. We reclassified current T1 to T1a and current T2 stage to T1b (1 to 2 cm and LP) and T2 (MP or greater than 2 cm). LN metastasis for T1b tumors was 4.7 per cent compared with 20.8 per cent for T2. The resulting TNM classification better defines 5-year disease-specific survival. Our modified staging schema identifies a low-risk group (T1a and T1b) that may be considered for local therapy.
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Affiliation(s)
- Swapnil D. Kachare
- From the Brody School of Medicine, Division of Surgical Oncology, East Carolina University, Greenville, North Carolina
| | - Kendall R. Liner
- From the Brody School of Medicine, Division of Surgical Oncology, East Carolina University, Greenville, North Carolina
| | - Nasreen A. Vohra
- From the Brody School of Medicine, Division of Surgical Oncology, East Carolina University, Greenville, North Carolina
| | - Emmanuel E. Zervos
- From the Brody School of Medicine, Division of Surgical Oncology, East Carolina University, Greenville, North Carolina
| | - Timothy L. Fitzgerald
- From the Brody School of Medicine, Division of Surgical Oncology, East Carolina University, Greenville, North Carolina
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45
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Exarchou K, Howes N, Pritchard DM. Systematic review: management of localised low-grade upper gastrointestinal neuroendocrine tumours. Aliment Pharmacol Ther 2020; 51:1247-1267. [PMID: 32390152 DOI: 10.1111/apt.15765] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 02/24/2020] [Accepted: 04/12/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Neuroendocrine tumours (NETs) of the stomach and duodenum are rare, but are increasing in incidence. Optimal management of localised, low-grade gastric and duodenal NETs remains controversial. AIMS To systematically review recent literature that has evaluated the management of localised low-grade gastric and duodenal NETs. METHODS A systematic literature search was conducted. Articles were screened and eligible articles fully assessed. Additional articles were identified through the included articles' reference lists. RESULTS Several relevant retrospective case series were identified, but there was considerable heterogeneity between studies and they reported a variety of parameters. Type I gastric NETs had an excellent prognosis and conservative management approaches such as endoscopic surveillance/resection were appropriate in most cases. Many type III gastric NETs were low grade and appeared to have a better prognosis than has previously been appreciated. Endoscopic rather than surgical resection was therefore effective in some patients who had small, low-grade tumours. Duodenal NETs were more heterogenous. Endoscopic resection was generally safe and effective in patients who had small, low-grade, nonfunctional, non-ampullary tumours. However, some patients, especially those with larger or ampullary duodenal NETs, required surgical resection. CONCLUSIONS Most type I gastric NETs behave indolently and surgical resection is only rarely indicated. Some type III gastric and duodenal NETs have a worse prognosis, but selected patients who have small, localised, nonfunctional, low-grade tumours are adequately and safely treated by endoscopic resection. Due to the complexity of this area, a multidisciplinary approach to management is strongly recommended.
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Affiliation(s)
- Klaire Exarchou
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Nathan Howes
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - David Mark Pritchard
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
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Mele C, Mencarelli M, Caputo M, Mai S, Pagano L, Aimaretti G, Scacchi M, Falchetti A, Marzullo P. Phenotypes Associated With MEN1 Syndrome: A Focus on Genotype-Phenotype Correlations. Front Endocrinol (Lausanne) 2020; 11:591501. [PMID: 33312161 PMCID: PMC7708377 DOI: 10.3389/fendo.2020.591501] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 10/16/2020] [Indexed: 12/21/2022] Open
Abstract
Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited tumor syndrome, associated with parathyroid, pituitary, and gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs). MEN1 is usually consequent to different germline and somatic mutations of the MEN1 tumor suppressor gene, although phenocopies have also been reported. This review analyzed main biomedical databases searching for reports on MEN1 gene mutations and focused on aggressive and aberrant clinical manifestations to investigate the potential genotype-phenotype correlation. Despite efforts made by several groups, this link remains elusive to date and evidence that aggressive or aberrant clinical phenotypes may be related to specific mutations has been provided by case reports and small groups of MEN1 patients or families. In such context, a higher risk of aggressive tumor phenotypes has been described in relation to frameshift and non-sense mutations, and predominantly associated with aggressive GEP NETs, particularly pancreatic NETs. In our experience a novel heterozygous missense mutation at c.836C>A in exon 6 was noticed in a MEN1 patient operated for macro-prolactinoma, who progressively developed recurrent parathyroid adenomas, expanding gastrinomas and, long after the first MEN1 manifestation, a neuroendocrine uterine carcinoma. In conclusion, proof of genotype-phenotype correlation is limited but current evidence hints at the need for long-term interdisciplinary surveillance in patients with aggressive phenotypes and genetically confirmed MEN1.
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Affiliation(s)
- Chiara Mele
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
- Istituto Auxologico Italiano, IRCCS, Division of General Medicine, S. Giuseppe Hospital, Piancavallo, Italy
| | - Monica Mencarelli
- Istituto Auxologico Italiano, IRCCS, Laboratory of Molecular Biology, S. Giuseppe Hospital, Piancavallo, Italy
| | - Marina Caputo
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Division of Endocrinology, University Hospital “Maggiore della Carità”, Novara, Italy
| | - Stefania Mai
- Istituto Auxologico Italiano, IRCCS, Laboratory of Metabolic Research, S. Giuseppe Hospital, Piancavallo, Italy
| | - Loredana Pagano
- Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Gianluca Aimaretti
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
- Division of Endocrinology, University Hospital “Maggiore della Carità”, Novara, Italy
| | - Massimo Scacchi
- Istituto Auxologico Italiano, IRCCS, Division of General Medicine, S. Giuseppe Hospital, Piancavallo, Italy
| | - Alberto Falchetti
- Istituto Auxologico Italiano, IRCCS, Rehabilitation Unit, S. Giuseppe Hospital, Unit for Bone Metabolism Diseases, Verbania, Italy
- Diabetes & Lab of Endocrine and Metabolic Research, Dept. of Clinical Sciences & Community Health, University of Milan, Milan, Italy
| | - Paolo Marzullo
- Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
- Istituto Auxologico Italiano, IRCCS, Division of General Medicine, S. Giuseppe Hospital, Piancavallo, Italy
- *Correspondence: Paolo Marzullo,
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Gamboa AC, Liu Y, Lee RM, Zaidi MY, Staley CA, Kooby DA, Winer JH, Shah MM, Russell MC, Cardona K, Maithel SK. Duodenal neuroendocrine tumors: Somewhere between the pancreas and small bowel? J Surg Oncol 2019; 120:1293-1301. [PMID: 31621090 DOI: 10.1002/jso.25731] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 09/22/2019] [Indexed: 01/21/2023]
Abstract
BACKGROUND While sub-2 cm pancreatic neuroendocrine tumors (NETs) are often observed, small bowel-NETs undergo resection and lymphadenectomy regardless of size. Aim was to define the natural history of duodenal (D-NETs), determine the role of resection, and define the factors associated with overall survival (OS) after resection. METHODS National Cancer Database (2004-2014) was queried for the patients with nonmetastatic/nonfunctional D-NETs. Local resection (LR): local excision/polypectomy/excisional biopsy. Anatomic resection (AR): radical surgery. Tumor size was divided into less than 1 cm, 1 to 2 cm, and ≥2 cm. Propensity score weighting was used to create balanced resection and no-resection cohorts. The primary endpoint was OS. RESULTS Among 5502 patient, the median age was 65 years. The median follow-up was 49 months. The median tumor size was 0.8 cm. Resection was performed in 72% (n = 3954; LR: 61%, AR: 39%). Lymph node (LN) resection was performed in 26% (43% had metastasis). A total of 74% had negative margins. Resection and no-resection cohorts were propensity score weighted for age/sex/race/Charlson-Deyo score/tumor grade (all independently associated with OS on multivariable analysis). Resection was associated with improved median OS compared to no resection in all sizes (<1 cm: median not reached vs 194 months; 1-2 cm: median not reached vs 56 months; >2 cm: median not reached vs 90 months; all P < .01). Subset analysis of each resection size cohort demonstrated that neither type of resection, LN retrieval, LN positivity, or margin status was associated with OS (all P > .05). CONCLUSION Patients with nonmetastatic and nonfunctional D-NETS should be considered for resection regardless of tumor size. Given the lack of prognostic value, the resection type and extent of LN retrieval should be tailored to each patient's clinical picture and safety profile.
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Affiliation(s)
- Adriana C Gamboa
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Yuan Liu
- Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Rachel M Lee
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Mohammad Y Zaidi
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Charles A Staley
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Joshua H Winer
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Mihir M Shah
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Maria C Russell
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Kenneth Cardona
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
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Lee L, Ramos-Alvarez I, Ito T, Jensen RT. Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome. Int J Mol Sci 2019; 20:5128. [PMID: 31623145 PMCID: PMC6829234 DOI: 10.3390/ijms20205128] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/08/2019] [Accepted: 10/13/2019] [Indexed: 02/07/2023] Open
Abstract
The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
| | | | - Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan.
| | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
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Alekberzade AV, Krylov NN, Garmanova TN, Shahbazov R, Azari F, Zuykova KS, Litovchenko ED. [Duodenal neuroendocrine tumors]. Khirurgiia (Mosk) 2019:87-95. [PMID: 31355821 DOI: 10.17116/hirurgia201907187] [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: 11/17/2022]
Abstract
Significant augmentation of the incidence of duodenal neuroendocrine tumors duodenum has been observed in recent decades. There are 5 histological types of these tumors: gastrinoma (50-60%), somatostatin-producing tumor (15%), inactive serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinoma (<3%) and gangliocytic paraganglioma (<2%). The majority of tumors are localized within the bulb and postbulbar part of duodenum, 20% are found in periampular area. Treatment strategy depends on dimensions, localization, histological class, stage and type of tumor. It is believed that endoscopic resection is permissible for small inactive tumors (G1) located above major duodenal papilla. The majority of other neoplasms requires surgical resection. Personal experience of various surgeons is limited by small group of patients. Therefore, it is necessary to summarize results for selection of optimal treatment.
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Affiliation(s)
- A V Alekberzade
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
| | - N N Krylov
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
| | - T N Garmanova
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
| | - R Shahbazov
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA
| | - F Azari
- Department of Surgery, University of Pennsylvania, Philadelphia PA, USA
| | - K S Zuykova
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
| | - E D Litovchenko
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
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Park SG, Lee BE, Kim GH, Park JW, Lee MW, Kim SJ, Choi CW, Lee S, Park DY. Risk factors for lymph node metastasis in duodenal neuroendocrine tumors: A retrospective, single-center study. Medicine (Baltimore) 2019; 98:e15885. [PMID: 31169696 PMCID: PMC6571284 DOI: 10.1097/md.0000000000015885] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/25/2019] [Accepted: 05/05/2019] [Indexed: 02/06/2023] Open
Abstract
Duodenal neuroendocrine tumors (NETs) are rare, and risk factors associated with lymph node (LN) metastasis are still not well defined. The aim of this study was to investigate risk factors of LN metastasis in duodenal NETs based on the final histopathologic results and clinical follow-up data.This study included a total of 44 duodenal NETs in 38 patients who underwent endoscopic or surgical resection between January 2008 and December 2015. Diagnosis of duodenal NETs was confirmed based on immunohistochemical staining of chromogranin A, synaptophysin, and CD56; the clinicopathologic records were collected at the time of the initial diagnosis of duodenal NETs.Most duodenal NETs were small (≤1 cm in 33 tumors), World Health Organization (WHO) grade G1 (in 32 tumors), limited to the mucosa and/or submucosa (in 40 tumors), and located at the duodenal bulb (in 32 tumors). Of 44 tumors, lymphovascular invasion was present in 4 (9.1%), and among 38 patients, LN metastasis was detected in 4 (10.5%). LN metastases were significantly associated with the non-bulb location, tumor size >10 mm, tumor invasion into the muscularis propria or deeper, WHO grade G2, and lymphovascular invasion. During the mean follow-up period of 54.5 months (range, 24-123 months), recurrence occurred in 1 patient.Non-bulb location, tumor size >10 mm, invasion beyond the submucosa, WHO grade G2, and lymphovascular invasion are risk factors of LN metastasis in duodenal NETs. These findings can help clinicians choose the appropriate therapeutic modality for duodenal NETs.
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Affiliation(s)
- Sang Gyu Park
- Department of Internal Medicine, Pusan National University School of Medicine
| | - Bong Eun Lee
- Department of Internal Medicine, Pusan National University School of Medicine
- Biomedical Research Institute, Pusan National University Hospital, Busan
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine
- Biomedical Research Institute, Pusan National University Hospital, Busan
| | - Joon Woo Park
- Department of Internal Medicine, Pusan National University School of Medicine
| | - Moon Won Lee
- Department of Internal Medicine, Pusan National University School of Medicine
- Biomedical Research Institute, Pusan National University Hospital, Busan
| | - Su Jin Kim
- Department of Internal Medicine, Pusan National University School of Medicine
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan
| | - Cheol Woong Choi
- Department of Internal Medicine, Pusan National University School of Medicine
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan
| | - Sojeong Lee
- Department of Pathology, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Do Youn Park
- Department of Pathology, Pusan National University School of Medicine, Busan, Republic of Korea
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