|
1
|
Christodoulidis G, Kouliou MN, Ragias D, Chatziisaak D, Agko ES, Schizas D, Zacharoulis D. Last decade of advances in gastric neuroendocrine tumors: Innovations, challenges, and future directions. World J Clin Oncol 2025; 16:104577. [DOI: 10.5306/wjco.v16.i5.104577] [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: 12/24/2024] [Revised: 02/27/2025] [Accepted: 03/10/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Gastric neuroendocrine tumors (G-NETs) are rare tumors originating from enterochromaffin-like cells, with an incidence of 0.4 per 100000 annually. There are three main types: (1) Type I, linked to chronic atrophic gastritis and hypergastrinemia, makes up 75%–80% of G-NETs; (2) Type II, associated with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia, comprises 5%; and (3) Type III, sporadic tumors with a higher metastatic potential, accounting for 15%–25%. Diagnosis involves endoscopy, biopsy, and histological examination. Additional methods include serum gastrin testing, immunohistochemistry, and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis. Type I treatment usually involves endoscopic resection (ER), with surgical resection for recurrence. Somatostatin analogs (SSAs) can reduce tumor size, and the prognosis is generally excellent. Type II treatment centers on surgical removal of the gastrinoma, with ER for smaller lesions and SSAs for symptom management. Type III requires surgical resection (partial or total gastrectomy) with lymph node dissection, and possibly chemotherapy. This type has a worse prognosis due to its aggressive nature. Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases, and ongoing research into immunotherapies is expanding future treatment options. Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types. Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment, particularly for those associated with less favorable cases.
AIM To improve diagnostic precision and treatment, particularly for those associated with less favorable cases.
METHODS A systematic search was conducted in PubMed, Scopus, and Web of Science until September 2024. Two independent reviewers screened titles, abstracts, and full texts for eligibility based on G-NET treatment in adults. Eligible studies included cohort studies, clinical trials, case series, and case reports, while in vitro, pediatric, and non-English studies were excluded. Relevant data were extracted independently, and disagreements were resolved through discussion. Study quality was assessed using appropriate tools.
RESULTS G-NETs are rare, classified into three types: (1) Type I; (2) Type II; and (3) Type III. Type I G-NETs, often associated with chronic atrophic gastritis, are typically slow-growing and low-grade, with favorable outcomes following surgical resection. Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES, showing moderate malignancy risk. Type III G-NETs, the most aggressive and least common, present with distant metastases and poor prognosis. Diagnosis relies on endoscopy, imaging, and biomarkers like chromogranin A. Treatment varies by type, ranging from ER to aggressive surgery and chemotherapy for advanced cases. Regular follow-up is essential to monitor recurrence, particularly for type III G-NETs.
CONCLUSION G-NETs require tailored diagnosis and treatment based on type and stage. Types I and II generally have better prognosis, while types III and IV are linked to poorer outcomes due to invasion and metastasis. Treatment strategies vary from ER for type I to extensive surgery for type III. Emerging therapies, like somatostatin analogs and peptide-receptor radionuclide therapies, show promise in advanced cases. Further research is essential to improve early diagnosis and treatment, particularly for high-risk lesions.
Collapse
Affiliation(s)
| | - Marina Nektaria Kouliou
- Department of Internal Medicine, General Hospital of Argolida-Hospital Unit of Nafplio, Nafplio 21100, Pelopónnisos, Greece
| | - Dimitrios Ragias
- Department of Oncology, 251 Air Force General Hospital, Athens 11525, Greece
| | - Dimitrios Chatziisaak
- Department of Surgery, Kantonsspital St.Gallen, St.Gallen 9000, Switzerland
- Department of Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne 1005, Switzerland
| | - Eirini Sara Agko
- Department of Intensive Care Unit, Asklepios Paulinen Clinic Wiesbaden, Wiesbaden 65197, Germany
| | - Dimitrios Schizas
- Department of Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Dimitrios Zacharoulis
- Department of General Surgery, University of Thessaly, Larisa 41110, Thessalia, Greece
| |
Collapse
|
|
2
|
Jang JO, Jang WJ, Choi CW, Choi EJ, Kim SJ, Ryu DG, Park SB, Chung JH, Lee SH, Hwang SH. A single center retrospective analysis of feasibility of diagnostic endoscopic resection for grade 1 or 2 gastric neuroendocrine tumors. Sci Rep 2025; 15:16315. [PMID: 40348849 PMCID: PMC12065875 DOI: 10.1038/s41598-025-99791-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 04/23/2025] [Indexed: 05/14/2025] Open
Abstract
Currently, endoscopic resection is recommended for gastric neuroendocrine tumors (G-NETs) < 10 mm. However, a larger G-NETs can also be resected endoscopically. Here, we evaluated the feasibility of diagnostic endoscopic resection of G-NETs. We retrospectively analyzed 31 patients, diagnosed with grade 1 or 2 G-NETs at a single tertiary referral center, between January 2009 and December 2023. Outcomes analyzed included histopathology, complete resection, and metastasis rates. The mean follow-up period was 38.9 ± 38.4 months; mean size of G-NETs was 4.9 ± 3.4 mm, and the most size of G-NETs were < 10 mm (87.1%). The maximal NET diameter was 16 mm. Most NETs were grade 1 (type 1: 90.9%; type 3: 85.0%). None of the enrolled patients showed evidence of lymph node metastasis or local recurrence. Even in R1 resection (19.4%) showed no metastasis during follow-up without additional surgery. Recurrent or multiple G-NETs were observed only in patients with type 1 NETs (27.2%, 3/11). Modified endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) showed a 100% complete resection rate. After resection, grade 1 or 2 G-NETs had no lymph nodes or distant metastases during the follow-up period. This study suggests that G-NETs smaller than 16 mm can be considered for diagnostic endoscopic resection and this resection may be potentially definitive treatment.
Collapse
Affiliation(s)
- Jin Ook Jang
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Won Jun Jang
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Cheol Woong Choi
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea.
| | - Eun Jeung Choi
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Su Jin Kim
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Dae Gon Ryu
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Su Bum Park
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Jae Hun Chung
- Department of Surgery, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Si Hak Lee
- Department of Surgery, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sun Hwi Hwang
- Department of Surgery, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| |
Collapse
|
|
3
|
Petrillo A, Ottaviano M, Pompella L, Giunta EF, Pisapia P, Marte G, Tufo A, Di Lorenzo S, Orefice J, Miceli C, Malapelle U, Daniele B, De Vita F. Rare epithelial gastric cancers: a review of the current treatment knowledge. Ther Adv Med Oncol 2025; 17:17588359241255628. [PMID: 39867743 PMCID: PMC11760139 DOI: 10.1177/17588359241255628] [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: 08/22/2023] [Accepted: 04/30/2024] [Indexed: 01/28/2025] Open
Abstract
Gastric cancer (GC), one of the tumours with the highest mortality worldwide, is not a homogeneous disease, showing different features according to location, macroscopic aspect, histotype and molecular alterations. Adenocarcinoma is the most frequent epithelial GC (95%), the remaining 5% comprising rare epithelial tumours with their peculiarities, behaviour and incidence <6 cases/100,000/year. Due to the low number of cases, many aspects must be elucidated in this context. In this narrative review, we highlight the importance of a better understanding of rare GCs to personalize the cures in the light of the precision medicine concept. Our main aim is to translate the scarce evidence from the literature into daily clinical practice, never forgetting that all the clinicians dedicated to rare GCs should encourage such patients' enrolment in clinical trials and promote international collaborations. Hence, we focused on the treatment of the following rare GCs: rare gastric adenocarcinomas (hepatoid adenocarcinoma, medullary carcinoma with lymphoid stroma, Paneth cell carcinoma and Salivary Gland carcinoma); squamous cell carcinoma; adenosquamous carcinoma; neuroendocrine gastric neoplasms; gastroblastoma.
Collapse
Affiliation(s)
- Angelica Petrillo
- Medical Oncology Unit, Ospedale del Mare, Via E. Russo, Naples 80147, Italy
| | - Margaret Ottaviano
- Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy
| | - Luca Pompella
- Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy
| | - Emilio Francesco Giunta
- Department of Experimental Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Pasquale Pisapia
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | | | - Andrea Tufo
- Surgical Unit, Ospedale del Mare, Naples, Italy
| | - Sara Di Lorenzo
- Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Jessica Orefice
- Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Chiara Miceli
- Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| | - Umberto Malapelle
- Department of Public Health, University of Naples Federico II, Naples, Italy
| | - Bruno Daniele
- Medical Oncology Unit, Ospedale del Mare, Naples, Italy
| | - Ferdinando De Vita
- Department of Precision Medicine, Università degli Studi della Campania ‘Luigi Vanvitelli’, Naples, Italy
| |
Collapse
|
|
4
|
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.
Collapse
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
| |
Collapse
|
|
5
|
Maly M, Callebout E, Ribeiro S, Hoorens A, Carton S, Cuyle PJ, Vandamme T, Borbath I, Demetter P, Van Damme N, Van Eycken L, Verslype C, Geboes K. Neuroendocrine tumors in the stomach: An epidemiological analysis of Belgian Cancer Registry data 2010-2019. J Neuroendocrinol 2025; 37:e13473. [PMID: 39604221 DOI: 10.1111/jne.13473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 10/15/2024] [Accepted: 11/10/2024] [Indexed: 11/29/2024]
Abstract
The prevalence of gastric NEN is estimated worldwide at 8.9% of all gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) and only 0.3%-1% of all gastric neoplasms, but is rising in the last decades. The aim of this project was to map the epidemiology of gastric neuroendocrine neoplasm (gNEN) in Belgium. This is a population-wide retrospective cohort study over 10 years (2010-2019), based on data from the Belgian Cancer Registry. A total of 641 patients were included; 605 patients with gNEN and 36 with MiNEN. The AAIR of gNEN was 0.67 per 100,000 person-years, increasing over the years and with a slight female predominance (55.4%). Neuroendocrine carcinoma (NEC) accounted for 15.7% (N = 95), with an AAIR of 0.11 per 100,000 person-years. The other 510 patients were diagnosed with gNET: G1 NET was most prevalent (54.3%) followed by G2 (32.5%) and G3 NET (3.5%). Concerning the clinical classification (type) of gNET, a diagnosis of type 1 tumors was presumed in 67.6%, type 3 tumors in 17.1% and type 2 tumors in 0.6% of patients. In only 3.8% of patients, the clinical classification was explicitly stated in the pathology report. Stage IV tumors were diagnosed in 13.4% (N = 81). A favorable evolution in pathology reporting is seen. Some variables-for example, clinical classification of gNET-were heavily underreported, stressing the importance of registries integrating clinical and pathological information.
Collapse
Affiliation(s)
- Marlies Maly
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Eduard Callebout
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Suzane Ribeiro
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Anne Hoorens
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
| | - Saskia Carton
- Department of Gastroenterology and Digestive Oncology, Imelda General Hospital, Bonheiden, Belgium
| | - Pieter-Jan Cuyle
- Department of Gastroenterology and Digestive Oncology, Imelda General Hospital, Bonheiden, Belgium
| | - Timon Vandamme
- NETwerk and Department of Oncology, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium
| | - Ivan Borbath
- Gastroenterology Department, UCLouvain, Louvain, Belgium
| | - Pieter Demetter
- Department of Pathology, Institut Jules Bordet, ULB, Brussels, Belgium
| | | | | | - Chris Verslype
- Department of Digestive Oncology, University Hospitals Leuven, Belgium
| | - Karen Geboes
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| |
Collapse
|
|
6
|
Sakurai Y, Karaki H, Nakamura Y, Fukuda H, Okaya T, Oheda Y, Yokoyama Y, Hirai F, Abe M, Sugano I. A case of early-stage type 3 gastric neuroendocrine tumor in the upper body of the stomach: is endoscopic resection feasible? Clin J Gastroenterol 2024; 17:814-819. [PMID: 38865017 DOI: 10.1007/s12328-024-01999-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 06/03/2024] [Indexed: 06/13/2024]
Abstract
Although gastric neuroendocrine tumors (NETs) are uncommon compared with gastric carcinomas, the incidence of NETs has been recently increasing. Gastric NETs are classified into three subgroups, and among these, gastrin-independent sporadic type 3 gastric NETs have a poor prognosis because of frequent lymph node or distant metastasis. We experienced a case of an early-stage type 3 gastric NET associated with lymphovascular and submucosal invasion. In a 54 year-old woman, esophagogastroduodenoscopy performed during a health screening identified an elevated lesion of the upper body of the stomach. The results of immunohistochemical analyses of endoscopic biopsy specimens obtained from the lesion were positive for chromogranin A and synaptophysin, indicating an NET. Because the patient's serum gastrin level was normal and she had no predisposing conditions for NET development, the tumor was diagnosed as a type 3 gastric NET. The patient underwent local resection of the tumor and regional lymph node dissection. The resected specimen indicated a diagnosis of type 3 gastric NET with invasion into the submucosa and lymphatic duct. This is an extremely rare case of an early-stage type 3 gastric NET. Our discussion provides insight into the pathogenesis and development of these tumors and the appropriate therapeutic strategy.
Collapse
Affiliation(s)
- Yoichi Sakurai
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan.
| | - Hirokazu Karaki
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yusuke Nakamura
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Hiroyuki Fukuda
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Tomohisa Okaya
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yoshio Oheda
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yuya Yokoyama
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Futoshi Hirai
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Michikazu Abe
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Isamu Sugano
- Pathology Division, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| |
Collapse
|
|
7
|
Nam K, Nam SY, Park JC, Cho YS, Choi HS, Jung K, Park SY, Cho JH, Chun H. Factors associated with gastric and duodenal neuroendocrine tumors: A multicenter case-control study. Dig Liver Dis 2024; 56:1592-1598. [PMID: 38369411 DOI: 10.1016/j.dld.2024.01.210] [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: 08/15/2023] [Revised: 01/26/2024] [Accepted: 01/26/2024] [Indexed: 02/20/2024]
Abstract
BACKGROUND AND AIMS The incidence of gastric and duodenal neuroendocrine tumors (GNET and DNET, respectively) is increasing, however associated factors of these diseases are not well known. Here, we investigated the factors associated with GNET and DNET. METHODS Patients with GNET and DNET presenting at eight tertiary referral centers between 2001 and 2020 were included and compared with healthy controls who underwent upper endoscopic screening. Clinical factors and laboratory data were analyzed to determine associated factors of GNET and DNET. RESULTS Overall, 396 patients with GNET and 193 patients with DNET were included and compared with 1725 healthy controls. Multivariate analysis showed that age (odds ratio [OR] 0.98), diabetes (OR 1.72), hypertension (OR 1.97), low serum high-density lipoprotein cholesterol (HDL-C) levels (OR 2.54), and past/present H. pylori infection (OR 1.46) were significantly associated with GNET. In contrast, DNET was significantly associated with diabetes (OR 1.80), hypertension (OR 1.68), low serum HDL-C levels (OR 2.29), and past/present H. pylori infection (OR 5.42). In the sex-based subgroup analysis in GNET, current smoking was strongly associated in women (OR 9.85), but not in men. CONCLUSIONS This study identified several common metabolic factors associated with GNET and DNET. Additionally, some factors had sex-specific associations.
Collapse
Affiliation(s)
- Kwangwoo Nam
- Department of Gastroenterology, Dankook University Hospital, Dankook University College of Medicine, Cheonan, South Korea
| | - Su Youn Nam
- School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, South Korea.
| | - Jun Chul Park
- Division of Gastroenterology, Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea
| | - Young Sin Cho
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan, South Korea
| | - Hyuk Soon Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Kyoungwon Jung
- Division of Gastroenterology, Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea
| | - Seon-Young Park
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea
| | - Joon Hyun Cho
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, South Korea
| | - Hyonho Chun
- Department of Mathematical Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea
| |
Collapse
|
|
8
|
Ortigão R, Afonso LP, Pimentel-Nunes P, Dinis-Ribeiro M, Libânio D. Predictors of Outcomes in Gastric Neuroendocrine Tumors: A Retrospective Cohort. GE PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2024; 31:236-245. [PMID: 39022301 PMCID: PMC11250119 DOI: 10.1159/000530684] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 02/02/2023] [Indexed: 07/20/2024]
Abstract
INTRODUCTION/AIM Gastric neuroendocrine tumors (GNETs) frequently have an indolent clinical course, despite their metastatic potential. The aim of the study was to identify prognostic factors associated with overall survival and risk of metastases and to evaluate the impact of serial measurements of chromogranin A (CgA). METHODS The authors performed a retrospective cohort study including consecutive patients with GNET diagnosed between 2010 and 2019, with a minimum follow-up of 1 year. Univariate and multivariate analyses were performed. RESULTS We included 132 patients with GNET (type I, 113 patients; type II, 1 patient; type III, 14 patients; type IV, 2 patients; not classifiable, 2 patients), with 61% being female and a mean age at diagnosis of 66 years. During the follow-up period (median 66 months), 3 (2.3%) patients died due to metastatic disease (1 patient with type III and 2 patients with type IV). Male gender (p = 0.030), type III/IV (p < 0.001), Ki-67 index >20% (p < 0.001), grade 2/3 (p < 0.001), invasion beyond the submucosa (p < 0.001), and presence of metastases (p < 0.001) were identified as risk factors for mortality in the univariate analysis. Metastasis developed in 7 patients (5.3%). Multivariable analysis revealed that Ki-67 >20% (p = 0.016) was an independent risk factor for metastasis. Overall, CgA showed a sensitivity of 20% for detection of recurrence and a specificity of 79% (sensitivity of 8% and specificity of 71% in type I GNETs). CONCLUSION Identification of risk factors for the presence of metastases and for mortality in these groups of patients can help in individualizing the therapeutic strategy. CgA seems to be a weak marker for monitoring patients with GNET.
Collapse
Affiliation(s)
- Raquel Ortigão
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Luís Pedro Afonso
- Department of Pathology, Portuguese Oncology Institute of Porto, Porto, Portugal
| | - Pedro Pimentel-Nunes
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal
- RISE@CI-IPOP (Health Research Network, IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), Porto, Portugal
- Unilabs Portugal, Porto, Portugal
| | - Mário Dinis-Ribeiro
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Diogo Libânio
- Gastroenterology Department, Portuguese Oncology Institute of Porto, Porto, Portugal
- MEDCIDS, Faculty of Medicine, University of Porto, Porto, Portugal
| |
Collapse
|
|
9
|
Panzuto F, Parodi MC, Esposito G, Massironi S, Fantin A, Cannizzaro R, Milione M, De Angelis CG, Annibale B. Endoscopic management of gastric, duodenal and rectal NETs: Position paper from the Italian Association for Neuroendocrine Tumors (Itanet), Italian Society of Gastroenterology (SIGE), Italian Society of Digestive Endoscopy (SIED). Dig Liver Dis 2024; 56:589-600. [PMID: 38216439 DOI: 10.1016/j.dld.2023.12.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 12/23/2023] [Accepted: 12/26/2023] [Indexed: 01/14/2024]
Abstract
The present paper reflects the position of the Italian Association for Neuroendocrine Tumors (Itanet), the Italian Society of Gastroenterology (SIGE), and the Italian Society of Digestive Endoscopy (SIED) regarding the management of patients affected by gastric, duodenal, and rectal neuroendocrine neoplasms (NENs) amenable to endoscopic treatment. The key questions discussed in this paper are summarized in Table 1. Data were extracted from the MEDLINE database through searches; expert opinions and recommendations are provided in accordance with the available scientific evidence and the authors' expertise. Recommendations are presented alongside a level of evidence and grade of recommendation based on the GRADE system. This paper specifically focuses on subgroups of NENs considered suitable for endoscopic management according to current international guidelines: i. well-differentiated gastric neuroendocrine tumors (gNET) type 1 < 2 cm and selected cases of type 3; ii. well-differentiated duodenal, non-functioning, non-ampullary NET with size < 2 cm; and well-differentiated rectal NET with size < 2 cm.
Collapse
Affiliation(s)
- Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy.
| | - Maria Caterina Parodi
- Department of Gastroenterology and Digestive Endoscopy, IRCCS Teaching Hospital San Martino, Genova, Italy
| | - Gianluca Esposito
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| | - Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Alberto Fantin
- Gastroenterology Unit; Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Renato Cannizzaro
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Italy; Department of Medical, Surgical and Health Sciences, University of Trieste, Italy
| | - Massimo Milione
- Pathology First Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy
| | - Claudio Giovanni De Angelis
- Gastroenterology Department, Endoscopy Unit, Azienda Ospedaliero Universitaria, Città della Salute e della Scienza di Torino, Turin, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Digestive Disease Unit, ENETS Center of Excellence, Sant'Andrea University Hospital, Rome, Italy
| |
Collapse
|
|
10
|
Han L, Li J, Liang C, Chu Y, Wang Y, Lv L, Liu D, Tan Y. Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors. Surg Endosc 2024; 38:2041-2049. [PMID: 38429572 DOI: 10.1007/s00464-024-10706-0] [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: 09/28/2023] [Accepted: 01/18/2024] [Indexed: 03/03/2024]
Abstract
BACKGROUND In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.
Collapse
Affiliation(s)
- Liu Han
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
- Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan, China
- Clinical Research Center for Digestive Diseases in Hunan Province, Changsha, 410011, Hunan, China
| | - Jianglei Li
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
- Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan, China
- Clinical Research Center for Digestive Diseases in Hunan Province, Changsha, 410011, Hunan, China
- Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410000, Hunan, China
| | - Chengbai Liang
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
- Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan, China
- Clinical Research Center for Digestive Diseases in Hunan Province, Changsha, 410011, Hunan, China
| | - Yi Chu
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
- Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan, China
- Clinical Research Center for Digestive Diseases in Hunan Province, Changsha, 410011, Hunan, China
| | - Yongjun Wang
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
- Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan, China
- Clinical Research Center for Digestive Diseases in Hunan Province, Changsha, 410011, Hunan, China
| | - Liang Lv
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
- Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan, China
- Clinical Research Center for Digestive Diseases in Hunan Province, Changsha, 410011, Hunan, China
| | - Deliang Liu
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
- Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan, China.
- Clinical Research Center for Digestive Diseases in Hunan Province, Changsha, 410011, Hunan, China.
| | - Yuyong Tan
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
- Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan, China.
- Clinical Research Center for Digestive Diseases in Hunan Province, Changsha, 410011, Hunan, China.
| |
Collapse
|
|
11
|
Sok C, Ajay PS, Tsagkalidis V, Kooby DA, Shah MM. Management of Gastric Neuroendocrine Tumors: A Review. Ann Surg Oncol 2024; 31:1509-1518. [PMID: 38062290 PMCID: PMC10922891 DOI: 10.1245/s10434-023-14712-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/20/2023] [Indexed: 01/30/2024]
Abstract
Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors.
Collapse
Affiliation(s)
- Caitlin Sok
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Pranay S Ajay
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Vasileios Tsagkalidis
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Mihir M Shah
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
| |
Collapse
|
|
12
|
Dell’Unto E, Esposito G, Rinzivillo M, Marasco M, Annibale B, Panzuto F. Type 3 gastric neuroendocrine neoplasms: the rising promise of conservative endoscopic management. Front Med (Lausanne) 2024; 11:1327864. [PMID: 38357651 PMCID: PMC10864619 DOI: 10.3389/fmed.2024.1327864] [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: 10/25/2023] [Accepted: 01/15/2024] [Indexed: 02/16/2024] Open
Abstract
Gastric neuroendocrine neoplasms (g-NENs) are rare tumors arising from the gastric enterochromaffin-like cells. Recent data suggests an increased detection rate, attributed to more frequent esophagogastroduodenoscopies. While type 3 g-NENs were historically deemed aggressive, emerging research indicates potential for conservative management, especially endoscopic resection, in well-differentiated, small tumors. European guidelines now advocate for endoscopic intervention in selected cases, but North American guidelines remain more conservative. Key factors influencing outcomes are tumor size, grading, and depth of gastric wall infiltration. Endoscopic resection has shown promise for tumors confined to submucosal layers without lymphovascular invasion. Given the complexities, a multidisciplinary team approach is essential for management decisions. Current insights are largely based on retrospective studies, underscoring the need for prospective research to optimize endoscopic approaches.
Collapse
Affiliation(s)
- Elisabetta Dell’Unto
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Gianluca Esposito
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Matteo Marasco
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
- PhD in Translational Medicine and Oncology, Sapienza University of Rome, Rome, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| |
Collapse
|
|
13
|
Chacchi-Cahuin R, Despott EJ, Lazaridis N, Rimondi A, Fusai GK, Mandair D, Anderloni A, Sciola V, Caplin M, Toumpanakis C, Murino A. Endoscopic Management of Gastro-Entero-Pancreatic Neuroendocrine Tumours: An Overview of Proposed Resection and Ablation Techniques. Cancers (Basel) 2024; 16:352. [PMID: 38254841 PMCID: PMC10814323 DOI: 10.3390/cancers16020352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/06/2024] [Accepted: 01/08/2024] [Indexed: 01/24/2024] Open
Abstract
A literature search of MEDLINE/PUBMED was conducted with the aim to highlight current endoscopic management of localised gastro-entero-pancreatic NETs. Relevant articles were identified through a manual search, and reference lists were reviewed for additional articles. The results of the research have been displayed in a narrative fashion to illustrate the actual state-of-the-art of endoscopic techniques in the treatment of NETs. Localised NETs of the stomach, duodenum and rectum can benefit from advanced endoscopic resection techniques (e.g., modified endoscopic mucosal resection, endoscopic full thickness resection, endoscopic submucosal dissection) according to centre expertise. Radiofrequency thermal ablation can be proposed as an alternative to surgery in selected patients with localised pancreatic NETs.
Collapse
Affiliation(s)
- Rocio Chacchi-Cahuin
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Edward J. Despott
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Nikolaos Lazaridis
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Alessandro Rimondi
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| | - Giuseppe Kito Fusai
- Department of HPB Surgery and Liver Transplant, Royal Free Hospital NHS Foundation Trust, London NW3 2QG, UK
| | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Andrea Anderloni
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy;
| | - Valentina Sciola
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Milano, 20122 Milan, Italy;
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, The Royal Free Hospital, Pond Street, London NW3 2QG, UK
| | - Alberto Murino
- Royal Free Unit for Endoscopy, The Royal Free Hospital and University College London (UCL) Institute for Liver and Digestive Health, London NW3 2QG, UK; (R.C.-C.)
| |
Collapse
|
|
14
|
Kim CG. Endoscopic Treatment for Gastric Subepithelial Tumor. J Gastric Cancer 2024; 24:122-134. [PMID: 38225771 PMCID: PMC10774759 DOI: 10.5230/jgc.2024.24.e11] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 12/21/2023] [Accepted: 12/21/2023] [Indexed: 01/17/2024] Open
Abstract
Most gastric subepithelial tumors (SETs) are asymptomatic and are often incidentally discovered during endoscopic procedures conducted for unrelated reasons. Although surveillance is sufficient for the majority of gastric SETs, certain cases necessitate proactive management. Laparoscopic wedge resection, although a viable treatment option, has its limitations, particularly in cases where SETs (especially those with intraluminal growth) are not visualized on the peritoneal side. Recent advances in endoscopic instruments and technology have paved the way for the feasibility of endoscopic resection of SETs. Several promising endoscopic techniques have emerged for gastric SET resection, including submucosal tunneling endoscopic resection, endoscopic full-thickness resection (EFTR), laparoscopic and endoscopic cooperative surgery (LECS), and non-exposure EFTR (non-exposed endoscopic wall-inversion surgery and non-exposure simple suturing EFTR). This study aimed to discuss the indications, methods, and outcomes of endoscopic therapy for gastric SETs. In addition, a simplified diagram of the category of SETs according to the therapeutic indications and an algorithm for the endoscopic management of SET is suggested.
Collapse
Affiliation(s)
- Chan Gyoo Kim
- National Cancer Center, Center for Gastric Cancer, Goyang, Korea.
| |
Collapse
|
|
15
|
Guo X, Zhao X, Huang G, Yu Y. Advances in Endoscopic Diagnosis and Treatment of Gastric Neuroendocrine Neoplasms. Dig Dis Sci 2024; 69:27-35. [PMID: 37971578 DOI: 10.1007/s10620-023-08180-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 11/01/2023] [Indexed: 11/19/2023]
Abstract
Gastric neuroendocrine neoplasms refer to a group of diseases that are relatively rare. They can be classified into three subtypes based on their clinical and histopathological features, and there are significant differences in diagnosis, treatment, and prognosis among the different subtypes. The incidence of gastric neuroendocrine neoplasms has been increasing globally in recent years with the localized disease being particularly evident. Gastrointestinal endoscopy is of irreplaceable importance for the diagnosis and management of g-NENs. Endoscopy with biopsy is the gold standard for the diagnosis of g-NENs. Ultrasound endoscopy can assess the depth of tumor invasion and the presence of lymphatic metastases, which is important for the development of treatment strategies. Meanwhile, for some small and low-risk lesions, endoscopic surveillance or endoscopic resection has satisfactory therapeutic results and prognosis. This means that even though the incidence has increased, advances in endoscopic techniques have allowed more patients to adopt a relatively conservative treatment strategy. However, the criteria for patients suitable for endoscopic surveillance or endoscopic resection remain controversial.
Collapse
Affiliation(s)
- Xinrui Guo
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Xiaohan Zhao
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Gang Huang
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China
| | - Yanbo Yu
- Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China.
- Shandong Provincial Clinical Research Center for Digestive Disease, Qilu Hospital of Shandong University, Jinan, Shandong, People's Republic of China.
| |
Collapse
|
|
16
|
Liu L, Liu W, Jia Z, Li Y, Wu H, Qu S, Zhu J, Liu X, Xu C. Application of machine learning algorithms to predict lymph node metastasis in gastric neuroendocrine neoplasms. Heliyon 2023; 9:e20928. [PMID: 37928390 PMCID: PMC10622622 DOI: 10.1016/j.heliyon.2023.e20928] [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: 02/23/2023] [Revised: 10/09/2023] [Accepted: 10/11/2023] [Indexed: 11/07/2023] Open
Abstract
Background Neuroendocrine neoplasms (NENs) are tumors that originate from secretory cells of the diffuse endocrine system and typically produce bioactive amines or peptide hormones. This paper describes the development and validation of a predictive model of the risk of lymph node metastasis among gastric NEN patients based on machine learning platform. Methods In this investigation, data from 1256 patients were used, of whom 119 patients from the First Affiliated Hospital of Soochow University in China and 1137 cases from the surveillance epidemiology and end results (SEER) database were combined. Six machine learning algorithms, including the logistic regression model (LR), random forest (RF), decision tree (DT), Naive Bayes (NB), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), were used to build the predictive model. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results Among the 1256 patients with gastric NENs, 276 patients (21.97 %) developed lymph node metastasis. T stage, tumor size, degree of differentiation, and sex were predictive factors of lymph node metastasis. The RF model achieved the best predictive performance among the six machine learning models, with an AUC, accuracy, sensitivity, and specificity of 0.81, 0.78, 0.76, and 0.82, respectively. Conclusion The RF model provided the best prediction and can help physicians determine the lymph node metastasis risk of gastric NEN patients to formulate individualized medical strategies.
Collapse
Affiliation(s)
- Lu Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Wen Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhenyu Jia
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yao Li
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Hongyu Wu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Shuting Qu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jinzhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiaolin Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chunfang Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| |
Collapse
|
|
17
|
Cavalcoli F, Gallo C, Coltro LA, Rausa E, Cantù P, Invernizzi P, Massironi S. Therapeutic Challenges for Gastric Neuroendocrine Neoplasms: Take It or Leave It? MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1757. [PMID: 37893475 PMCID: PMC10608689 DOI: 10.3390/medicina59101757] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 09/23/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023]
Abstract
Background and Objectives: Gastric neuroendocrine neoplasms (gNENs) represent rare but increasingly recognized tumors. They are distinguished into three main clinical types (type-1, type-2, and type-3) according to gastrin level and at histological evaluation in well-differentiated G1, G2, or G3 lesions, as well as poorly-differentiated lesions. Small type-1 and type-2 neoplasms with low proliferation indices demonstrated excellent survival without progression during an extended follow-up period, and for these reasons, active endoscopic observation or endoscopic resection are feasible options. On the other hand, surgery is the treatment of choice for more aggressive type-3, G3, or infiltrating neoplasms. The present study aims to comprehensively review and compare the available therapeutic strategies for gNENs. Materials and Methods: A computerized literature search was performed using relevant keywords to identify all of the pertinent articles with particular attention to gNEN endoscopic treatment. Results: In recent years, different endoscopic resective techniques (such as endoscopic mucosal dissection, modified endoscopic mucosal resection, and endoscopic full-thickness resection) have been developed, showing a high rate of complete resection for advanced and more aggressive lesions. Conclusions: Overall, gNENs represent a heterogeneous group of lesions with varying behavior which require personalized management. The non-operative approach for small type-1 gNENs seems to be feasible and should be promoted. A step-up approach with minimally invasive endoscopic therapies might be proposed, particularly for type-1 gNEN. On the other hand, it is important to recognize the negative prognostic factors in order to identify those rare cases requiring more aggressive approaches. A possible therapeutic algorithm for localized gNEN management is provided.
Collapse
Affiliation(s)
- Federica Cavalcoli
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (F.C.); (P.C.)
| | - Camilla Gallo
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Lorenzo Andrea Coltro
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Emanuele Rausa
- Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy;
| | - Paolo Cantù
- Gastroenterology and Digestive Endoscopy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (F.C.); (P.C.)
| | - Pietro Invernizzi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
| | - Sara Massironi
- Division of Gastroenterology, Fondazione IRCCS San Gerardo dei Tintori, University of Milano-Bicocca School of Medicine, 20900 Monza, Italy; (C.G.)
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, ASST Monza, 20900 Monza, Italy
| |
Collapse
|
|
18
|
Esposito G, Dell'Unto E, Ligato I, Marasco M, Panzuto F. The meaning of R1 resection after endoscopic removal of gastric, duodenal and rectal neuroendocrine tumors. Expert Rev Gastroenterol Hepatol 2023; 17:785-793. [PMID: 37497604 DOI: 10.1080/17474124.2023.2242261] [Citation(s) in RCA: 8] [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: 04/15/2023] [Revised: 05/26/2023] [Accepted: 07/25/2023] [Indexed: 07/28/2023]
Abstract
INTRODUCTION Well-differentiated gastric, duodenal, and rectal neuroendocrine neoplasms (NETs) are rare diseases usually managed by endoscopic treatment. Although several endoscopic techniques are available, the number of patients with incomplete (R1) resection is significant. AREAS COVERED This review focuses on the meaning of incomplete R1 findings after endoscopic resection in type I gastric NETs; nonfunctioning, non-ampullary duodenal NETs; and small rectal NETs. Data were identified by MEDLINE database search without publication date limitation. EXPERT OPINION An incomplete R1 finding may have no significant impact on a patient's clinical outcome, particularly in small G1 type I gastric NETs, which have an indolent course. A 'stepwise approach,' which uses more advanced endoscopic techniques, or minimally invasive surgery may be justified to achieve complete margin-free resection. This approach must balance the tumor features and the procedure-related risk of complications, particularly in the duodenum, where the role of deep endoscopic resections is limited due to the thin duodenal wall. Gastric and rectal NETs that are incompletely removed after initial resection are more easily amenable to deep endoscopic techniques. However, this might not be necessary for patients with comorbidities, elderly, or both due to the uncertainty of how R1 finding impacts a patient's clinical outcome.
Collapse
Affiliation(s)
- Gianluca Esposito
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| | - Elisabetta Dell'Unto
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| | - Irene Ligato
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| | - Matteo Marasco
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| | - Francesco Panzuto
- ENETS Center of ExcellenceDepartment of Medical-Surgical Sciences, Translational Medicine Sapienza University of Rome, Digestive Disease Unit - Sant'andrea University Hospital, Rome, Italy
| |
Collapse
|
|
19
|
Laffi A, Lania AGA, Ragni A, Di Vito V, Liccardi A, Rubino M, Sesti F, Colao A, Faggiano A. Gastric Neuroendocrine Tumors (g-NETs): A Systematic Review of the Management and Outcomes of Type 3 g-NETs. Cancers (Basel) 2023; 15:cancers15082202. [PMID: 37190131 DOI: 10.3390/cancers15082202] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 04/04/2023] [Accepted: 04/06/2023] [Indexed: 05/17/2023] Open
Abstract
PURPOSE to collect data from real-life experiences of the management of type 3 g-NETs and identify possible prognostic factors that may impact the decision-making process. METHODS We performed a systematic review of the literature on type 3 g-NET management using the PubMed, MEDLINE, and Embase databases. We included cohort studies, case series, and case reports written in the English language. RESULTS We selected 31 out of 556 articles from between 2001 and 2022. In 2 out of the 31 studies, a 10 mm and 20 mm cut-off size were respectively associated with a higher risk of gastric wall infiltration and/or lymph node and distant metastasis at diagnosis. The selected studies reported a higher risk of lymph node or distant metastasis at diagnosis in the case of muscularis propria infiltration or beyond, irrespective of the dimensions or grading. From these findings, size, grading, and gastric wall infiltration seem to be the most relevant factors in management staff making choices and prognoses of type 3 g-NET patients. We produced a hypothetical flowchart for a standardized approach to these rare diseases. CONCLUSION Further prospective analyses are needed to validate the prognostic impact of the use of size, grading, and gastric wall infiltration as prognostic factors in the management of type 3 g-NETs.
Collapse
Affiliation(s)
- Alice Laffi
- Hematology and Oncology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Andrea Gerardo Antonio Lania
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy
- Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Alberto Ragni
- Endocrinologia e Malattie Metaboliche, AO SS Antonio e Biagio e Cesare Arrigo, Via Venezia, 16, 15121 Alessandria, Italy
| | - Valentina Di Vito
- Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy
| | - Alessia Liccardi
- Operative Unit of Endocrinology, Department of Clinical Medicine and Surgery, Andrology and Diabetology, Federico II University of Naples, 80131 Naples, Italy
| | - Manila Rubino
- Servizio di Endocrinologia Oncologica, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 435, 20141 Milan, Italy
| | - Franz Sesti
- Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy
| | - Annamaria Colao
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University Federico II, 80126 Naples, Italy
- UNESCO "Education for Health and Sustainable Development", Federico II University, 80131 Naples, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, ENETS Center of Excellence, Sapienza University of Rome, 00185 Rome, Italy
| |
Collapse
|
|
20
|
Nabi Z, Lakhtakia S, Reddy DN. Current status of the role of endoscopy in evaluation and management of gastrointestinal and pancreatic neuroendocrine tumors. Indian J Gastroenterol 2023; 42:158-172. [PMID: 37129761 DOI: 10.1007/s12664-023-01362-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 02/15/2023] [Indexed: 05/03/2023]
Abstract
The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased over the last several decades. In general, NETs are slow-growing neoplasms and the data on the natural history is still evolving. The availability and improved utilization of advanced imaging modalities have allowed the selection of cases suitable for endotherapy. In this regard, endoscopic ultrasound (EUS) has emerged as a central imaging modality to assess the depth of infiltration in gastroduodenal as well as rectal NETs. Enhanced EUS modalities, including contrast-enhanced EUS and EUS elastography, reliably differentiate pancreatic neuroendocrine tumors (PNETs) from adenocarcinomas and may enable prediction of aggressive PNETs. With recent developments in therapeutic endoscopy, a large proportion of GEP-NETs can be safely managed endoscopically. Endoscopic resection techniques, including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), allow the safe removal of gastroduodenal and rectal NETs. Recent data indicate that modified EMR techniques may be superior to conventional EMR with regard to histologically complete resection. Device-assisted endoscopic full thickness resection is emerging as a safe and effective technique for upper gastrointestinal as well as rectal NETs. In selected cases with PNETs, who are otherwise unfit for surgery, EUS-guided ablation is increasingly being recognized as a safe treatment option. This review focusses on evidence-based approaches to endoscopic evaluation and the management of GEP-NETs with special emphasis on recent advancements.
Collapse
Affiliation(s)
- Zaheer Nabi
- Asian Institute of Gastroenterology, Hyderabad, 500 082, India.
| | | | | |
Collapse
|
|
21
|
Massironi S, Gallo C, Laffusa A, Ciuffini C, Conti CB, Barbaro F, Boskoski I, Dinelli ME, Invernizzi P. Endoscopic techniques for gastric neuroendocrine tumors: An update. World J Gastrointest Endosc 2023; 15:103-113. [PMID: 37034968 PMCID: PMC10080559 DOI: 10.4253/wjge.v15.i3.103] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 01/11/2023] [Accepted: 02/08/2023] [Indexed: 03/16/2023] Open
Abstract
Gastric neuroendocrine neoplasms (gNENs) are a rare type of gastric neoplasm, even if their frequency is increasing according to the latest epidemiologic revisions of the main registries worldwide. They are divided into three main subtypes, with different pathogeneses, biological behaviors, and clinical characteristics. GNEN heterogeneity poses challenges, therefore these neoplasms require different management strategies. Update the knowledge on the endoscopic treatment options to manage g-NENs. This manuscript is a narrative review of the literature. In recent years, many advances have been made not only in the knowledge of both the pathogenesis and the molecular profiling of gNENs but also in the endoscopic expertise towards innovative treatment options, which proved to be less aggressive without losing the capability of being radical. The endoscopic approach is increasingly applied in the field of gastrointestinal (GI) luminal neoplasms, and this is true not only for adenocarcinomas but also for gNENs. In particular, different techniques have been described for the endoscopic removal of suspected lesions, ranging from classical polypectomy (cold or hot snare) to endoscopic mucosal resection (both with "en bloc" or piecemeal technique), endoscopic submucosal dissection, and endoscopic full-thickness resection. GNENs comprise different subtypes of neoplasms with distinct management and prognosis. New endoscopic techniques offer a wide variety of approaches for GI localized neoplasms, which demonstrated to be appropriate and effective also in the case of gNENs. Correct evaluation of size, site, morphology, and clinical context allows the choice of tailored therapy in order to guarantee a definitive treatment.
Collapse
Affiliation(s)
- Sara Massironi
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Camilla Gallo
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Alice Laffusa
- Interventional Endoscopy Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Cristina Ciuffini
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore di Roma, Center for Endoscopic Research Therapeutics and Training (CERTT), Roma 00168, Italy
| | - Clara Benedetta Conti
- Interventional Endoscopy Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Federico Barbaro
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore di Roma, Center for Endoscopic Research Therapeutics and Training (CERTT), Roma 00168, Italy
| | - Ivo Boskoski
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore di Roma, Center for Endoscopic Research Therapeutics and Training (CERTT), Roma 00168, Italy
| | - Marco Emilio Dinelli
- Interventional Endoscopy Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| | - Pietro Invernizzi
- Gastroenterology Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB) 20900, Italy
| |
Collapse
|
|
22
|
Liang J, Jiang Y, Abboud Y, Gaddam S. Role of Endoscopy in Management of Upper Gastrointestinal Cancers. Diseases 2022; 11:diseases11010003. [PMID: 36648868 PMCID: PMC9844461 DOI: 10.3390/diseases11010003] [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: 09/21/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
Upper gastrointestinal (GI) malignancy is a leading cause of cancer-related morbidity and mortality. Upper endoscopy has an established role in diagnosing and staging upper GI cancers, screening for pre-malignant lesions, and providing palliation in cases of advanced malignancy. New advances in endoscopic techniques and technology have improved diagnostic accuracy and increased the therapeutic potential of upper endoscopy. We aim to describe the different types of endoscopic technology used in cancer diagnosis, summarize the current guidelines for endoscopic diagnosis and treatment of malignant and pre-malignant lesions, and explore new potential roles for endoscopy in cancer therapy.
Collapse
|
|
23
|
Ryu DG, Kim SJ, Choi CW, Kang DH, Kim HW, Park SB, Nam HS, Lee SH, Hwang SH. Clinical outcomes of gastroduodenal neuroendocrine tumors according to their WHO grade: A single-institutional retrospective analysis. Medicine (Baltimore) 2022; 101:e30397. [PMID: 36123854 PMCID: PMC9478211 DOI: 10.1097/md.0000000000030397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The management of gastroduodenal neuroendocrine tumor (NET) has been controversial between radical surgical resection and local excision including endoscopic resection. A gastroduodenal NET grade (G), measured by their mitotic rate and Ki67 proliferation index, is important to predict prognosis. In this study, we aimed to compare the clinical outcomes of gastroduodenal NET according to grades in order to identify poor prognostic factors of gastroduodenal NETs. Fifty-four gastroduodenal NETs diagnosed between December 2008 and December 2020 in a tertiary referral hospital were retrospectively reviewed. The clinical outcomes of gastroduodenal NETs, according to tumor grades and factors associated with NET G2-3, were analyzed. A total of 52 gastroduodenal NET patients was enrolled. The mean follow-up period was 56.2 ± 40.1 months. The mean size of gastric and duodenal NET was 7.9 ± 11.0 mm and 9.8 ± 7.6 mm, respectively. During the study period, 72.7% (16/22) of gastric NETs and 83.3% (25/30) of duodenal NETS were G1. All G1 gastroduodenal NETs showed no lymph node or distant metastasis during the study periods. All G3 gastroduodenal NETs showed metastasis (one lymph node metastasis and 3 hepatic metastases). Among metastatic NETs, the smallest tumor size was a 13 mm gastric G3 NET. Factors associated with G2-3 NETs were larger tumor size, mucosal ulceration, proper muscle or deeper invasion, and lymphovascular invasion. A small-sized gastroduodenal NET confined to submucosa without surface ulceration may be suitable for endoscopic resection. After local resection of a gastroduodenal NET (G1) without lymphovascular and muscle proper invasion, follow-up examination without radical surgical resection can be recommended. G3 NETs may be treated by radical surgical resection, regardless of tumor size.
Collapse
Affiliation(s)
- Dae Gon Ryu
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Su Jin Kim
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Cheol Woong Choi
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
- *Correspondence: Cheol Woong Choi, Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Korea (e-mail: or )
| | - Dae Hwan Kang
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Hyung Wook Kim
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Su Bum Park
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Hyeong Seok Nam
- Department of Internal Medicine, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Si Hak Lee
- Department of Surgery, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sun Hwi Hwang
- Department of Surgery, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| |
Collapse
|
|
24
|
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.
Collapse
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
| |
Collapse
|
|
25
|
Rossi RE, Elvevi A, Gallo C, Palermo A, Invernizzi P, Massironi S. Endoscopic techniques for diagnosis and treatment of gastro-entero-pancreatic neuroendocrine neoplasms: Where we are. World J Gastroenterol 2022; 28:3258-3273. [PMID: 36051341 PMCID: PMC9331536 DOI: 10.3748/wjg.v28.i26.3258] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/04/2022] [Accepted: 04/15/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The correct localization of the primary tumor site and a complete histological diagnosis represent the milestones for the proper management of gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs). AIM To analyze current evidence on the role of endoscopy in the diagnosis/treatment of GEP-NENs. METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature (retrospective and prospective studies, systematic reviews, case series) published in the last 15 years, using both medical subject heading (MeSH) terms and free-language keywords: gastro-entero-pancreatic neuroendocrine neoplasms; endoscopy; ultrasound endoscopy; capsule endoscopy; double-balloon enteroscopy; diagnosis; therapy; staging. RESULTS In the diagnostic setting, endoscopic ultrasonography (EUS) represents the diagnostic gold standard for pancreatic NENs and the technique of choice for the locoregional staging of gastric, duodenal and rectal NENs. The diagnosis of small bowel NENs (sbNENs) has been improved with the advent of video capsule endoscopy and double-balloon enteroscopy, which allow for direct visualization of the entire small bowel; however, data regarding the efficacy/safety of these techniques in the detection of sbNENs are scanty and often inconclusive. From a therapeutic point of view, endoscopic removal is the treatment of choice for the majority of gastric NENs (type 1/2), for well-differentiated localized nonmetastatic duodenal NENs < 1 cm, confined to the submucosa layer and for < 10 mm, stage T1-T2, rectal NENs. EUS-guided pancreatic locoregional ablative treatments have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients. CONCLUSION Standard axial endoscopy and EUS still play a pivotal role in several GEP-NENs. Advanced techniques for increasing the rate of R0 resection should be reserved for high-volume referral centers.
Collapse
Affiliation(s)
- Roberta Elisa Rossi
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Camilla Gallo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Andrea Palermo
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
| |
Collapse
|
|
26
|
Metastasis Prevalence and Survival of Patients with T1-2 Gastric Neuroendocrine Tumor Treated with Endoscopic Therapy and Surgery. Dig Dis Sci 2022; 67:3228-3238. [PMID: 34272627 DOI: 10.1007/s10620-021-07143-7] [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: 01/01/2021] [Accepted: 06/21/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM The selection criteria and long-term outcomes of endoscopic therapy (ET) for gastric neuroendocrine tumors (G-NETs) remain controversial. METHODS Using Surveillance, Epidemiology, and End Results (SEER) Program database, we assessed the prevalence of metastasis of early G-NETs and long-term outcomes of ET in G-NET patients with good/moderate differentiation and no muscularis propria (MP) involvement. RESULTS A total of 2207 patients with stage T1 and T2 G-NETs were included. The depth of invasion into MP [odds ratio (OR) 4.581, 95% confidence interval (CI) 2.571-8.162; P < 0.001] and size of > 20 mm (OR 5.656, 95% CI 2.002-15.975; P = 0.001) were significantly associated with metastasis. The 5-year overall survival (OS) and cancer-specific survival (CSS) of the ET group were similar to the surgery group (91.11% vs. 91.09%, P = 0.750; 99.26% vs. 99.01%, P = 0.173). In the multivariable Cox proportional hazards regression models adjusting for age, gender, race, year of diagnosis, SEER region, depth of tumor invasion, site of cancer, tumor size, and chemotherapy, procedures employed (ET or surgery) had no significant impact on the OS [hazard ratio (HR) 1.189; 95%CI 0.721-1.961; P = 0.498] and CSS (HR 0.684; 95% CI 0.021-22.727; P = 0.832). CONCLUSIONS The long-term outcome of survival did not appear to differ between ET and surgery in G-NETs with good/moderate differentiation, ≤ 20 mm size, and no MP involvement.
Collapse
|
|
27
|
Canakis A, Lee LS. Current updates and future directions in diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Endosc 2022; 14:267-290. [PMID: 35719897 PMCID: PMC9157694 DOI: 10.4253/wjge.v14.i5.267] [Citation(s) in RCA: 3] [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: 12/31/2021] [Revised: 02/14/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered, often incidentally, throughout the gastrointestinal tract with varying degrees of activity and malignant potential. Confusing nomenclature has added to the complexity of managing these lesions. The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm, which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms. A comprehensive multidisciplinary approach is important for clinicians to diagnose, stage and manage these lesions. While histological diagnosis is the gold standard, recent advancements in endoscopy, conventional imaging, functional imaging, and serum biomarkers complement histology for tailoring specific treatment options. In light of developing technology, our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors, including innovations in radiolabeled peptide imaging, circulating biomarkers, and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.
Collapse
Affiliation(s)
- Andrew Canakis
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Linda S Lee
- Division of Gastroenterology Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
| |
Collapse
|
|
28
|
Risk factors for metastasis and survival of patients with T1 gastric neuroendocrine carcinoma treated with endoscopic therapy versus surgical resection. Surg Endosc 2022; 36:6162-6169. [PMID: 35507062 PMCID: PMC9283353 DOI: 10.1007/s00464-022-09190-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 03/07/2022] [Indexed: 11/16/2022]
Abstract
Background Gastrectomy with lymphadenectomy is recommended for early gastric Neuroendocrine carcinoma (G-NEC). We attempted to determine the prevalence and risk factors of metastasis of T1 G-NEC and compare the long-term survival of patients after receiving endoscopic therapy (ET) and radical surgery. Methods In this study, 205 patients in total with T1 G-NEC were collected from the Surveillance Epidemiology and End Result database. Independent predictors of metastasis were identified by Logistic regression analysis, followed by the calculation of both cancer-specific survival (CSS) and overall survival (OS). Results Twenty-five patients (12.2%) were burdened with metastasis at initial diagnosis, with a prevalence of 5.2% (3/58) in mucosa lesions and 16.2% (16/99) in submucosa lesions (P = 0.045). No metastasis was detected in lesions with mucosa involvement and tumors ≦ 20 mm (0%, 0/49). The most significant risk factor for metastasis was tumors > 20 mm [odds ratio (OR) 18.64; 95% confidence interval (CI) 4.01–86.68; P < 0.001]. For patients with T1N0M0 G-NEC who received ET or surgery, the 10-year OS was similar between the mucosa extension and submucosa extension groups, which was 91.56% in ET group vs 87.50% in surgery group (P = 0.62) and 57.33% vs 77.83% (P = 0.11), respectively. In addition, the 10-year CSS was also similar between the mucosa extension and submucosa extension groups with 97.30% in ET vs 100% in surgery (P = 0.51) and 97.62% vs 86.49% (P = 0.65). Conclusions In G-NEC, tumors > 20 mm were considered as the most significant risk factor for metastasis. ET seemed adequate for the lesions with mucosa involvement and size ≦ 2 cm.
Collapse
|
|
29
|
Zhu C, Kawachi H, Lu X. A rare gastric lesion: diminutive, well-differentiated, Grade 3, type 3 gastric neuroendocrine tumor with extremely high ki-67 index removed en bloc under endoscopy. Gastric Cancer 2022; 25:659-664. [PMID: 35179666 DOI: 10.1007/s10120-022-01277-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 01/10/2022] [Indexed: 02/07/2023]
Abstract
Grade 3, type 3 gastric neuroendocrine tumor (g-NET) shows specific features of clinical interest and the therapeutic management of the lesion is not yet completely standardized. We present the unusual case of a 34-year-old male patient with a diminutive (less than 0.5 cm), well-differentiated, G3, type 3g-NET with extremely high Ki-67 index (higher than 80%). The lesion was subsequently removed en bloc via endoscopic submucosal dissection. Regarding the proliferation rate, Ki-67 index values usually range from 21 to 50%, and less commonly above 55%, in G3 NET. To our knowledge, this lesion represents a small size with the highest Ki-67 index diagnosed with G3 g-NET. However, as g-NET might recur even after a long duration, we recommend a long-term follow-up, such as 10 years after complete resection in patients to evaluate the endoscopic resection approach.
Collapse
Affiliation(s)
- Chunpeng Zhu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Hiroshi Kawachi
- Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Xinliang Lu
- Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
| |
Collapse
|
|
30
|
How to Select Patients Affected by Neuroendocrine Neoplasms for Surgery. Curr Oncol Rep 2022; 24:227-239. [PMID: 35076884 DOI: 10.1007/s11912-022-01200-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/10/2021] [Indexed: 11/03/2022]
|
|
31
|
Abstract
Purpose of Review Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach cancer. The three main subtypes have different pathogeneses, biological behaviours and clinical characteristics, so they require different management strategies. This article will provide an overview of g-NENs and highlight recent advances in the field. Recent Findings Molecular profiling has revealed differences between indolent and aggressive g-NENs, as well as a new somatic mutation responsible for some familial type I g-NENs. Novel biomarkers have been developed which will hopefully improve diagnosis, treatment, risk stratification and follow-up. Patient treatment is also changing, as evidence supports the use of less aggressive options (e.g. endoscopic surveillance or resection) in some patients with more indolent tumours. Summary g-NEN heterogeneity poses challenges in understanding and managing this rare disease. More basic science research is needed to investigate molecular pathogenesis, and future larger clinical studies will hopefully also further improve treatment and patient outcomes.
Collapse
|
|
32
|
Exarchou K, Kamieniarz L, Tsoli M, Victor A, Oleinikov K, Khan MS, Srirajaskanthan R, Mandair D, Grozinsky-Glasberg S, Kaltsas G, Howes N, Pritchard DM, Toumpanakis C. Is local excision sufficient in selected grade 1 or 2 type III gastric neuroendocrine neoplasms? Endocrine 2021; 74:421-429. [PMID: 34120313 DOI: 10.1007/s12020-021-02775-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/23/2021] [Indexed: 02/07/2023]
Abstract
PURPOSE Type III gastric neuroendocrine neoplasms (g-NENs) have historically been regarded as aggressive tumours, hence current guidelines advocate radical surgery with lymph node dissection. Data on the roles of endoscopic or less extensive surgical resections are more limited. The aim of our study is to evaluate the clinicopathological features and long-term outcomes of patients undergoing endoscopic or limited surgical resection for localised grade 1 or 2 type III g-NENs when compared to radical surgery. METHODS Retrospective analysis of all patients diagnosed with a localised grade 1 or 2 type III g-NENs across six tertiary NEN centers between 2006 and 2019. RESULTS Forty-five patients were diagnosed with a potentially resectable grade 1 or 2 type III g-NEN of whom 36 underwent either endoscopic or surgical resection. No statistically significant differences were found between the three resection groups in terms of patient age, tumour location, grade or size. Only tumour size was found to be significantly associated with poor clinical outcome (p = 0.012) and ROC curve analysis identified tumour size >10 mm as a negative predictor (AUC:0.8030, p = 0.0021). Tumours >10 mm were also more likely to be associated with lymph node metastases on imaging and histology (p = 0.039 and p = 0.026 respectively). CONCLUSIONS Localised grade 1 or 2 type III g-NENs had a good prognosis in this series. Tumour size >10 mm was the most significant prognostic factor affecting patient outcome. Endoscopic resection or limited surgical resection is feasible and safe in small type III g-NENs which demonstrate favourable grade 1/2, well differentiated histology.
Collapse
Affiliation(s)
- Klaire Exarchou
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool ENETS Centre of Excellence, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
- Department of Upper Gastrointestinal Surgery, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Lukasz Kamieniarz
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free Hospital, London, UK
| | - Marina Tsoli
- 1st Department of Propaedeutic Internal Medicine, Endocrine Oncology Unit, ENETS Centre of Excellence, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexandra Victor
- South Wales NET Service, Department of Gastroenterology, University Hospital of Wales, Cardiff, UK
| | - Kira Oleinikov
- Neuroendocrine Tumor Unit, ENETS Center of Excellence, Endocrinology & Metabolism Department, Division of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Mohid S Khan
- South Wales NET Service, Department of Gastroenterology, University Hospital of Wales, Cardiff, UK
| | - Raj Srirajaskanthan
- Department of Gastroenterology, Institute of Liver studies, Kings College Hospital, ENETS Centre of Excellence, London, UK
| | - Dalvinder Mandair
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free Hospital, London, UK
| | - Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, ENETS Center of Excellence, Endocrinology & Metabolism Department, Division of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Gregory Kaltsas
- 1st Department of Propaedeutic Internal Medicine, Endocrine Oncology Unit, ENETS Centre of Excellence, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Nathan Howes
- Department of Upper Gastrointestinal Surgery, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - D Mark Pritchard
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool and Liverpool ENETS Centre of Excellence, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free Hospital, London, UK.
| |
Collapse
|
|
33
|
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.
Collapse
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
| |
Collapse
|
|
34
|
Köseoğlu H, Duzenli T, Sezikli M. Gastric neuroendocrine neoplasms: A review. World J Clin Cases 2021; 9:7973-7985. [PMID: 34621854 PMCID: PMC8462212 DOI: 10.12998/wjcc.v9.i27.7973] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [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: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.
Collapse
Affiliation(s)
- Hüseyin Köseoğlu
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
| | - Tolga Duzenli
- Department of Gastroenterology, Hitit University Erol Olçok Education and Research Hospital, Çorum 19200, Turkey
| | - Mesut Sezikli
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
| |
Collapse
|
|
35
|
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.
Collapse
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
| |
Collapse
|
|
36
|
Hanna A, Kim-Kiselak C, Tang R, Metz DC, Yang Z, DeMatteo R, Fraker DL, Roses RE. Gastric Neuroendocrine Tumors: Reappraisal of Type in Predicting Outcome. Ann Surg Oncol 2021; 28:8838-8846. [PMID: 34120268 DOI: 10.1245/s10434-021-10293-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/25/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Type I gastric neuroendocrine tumors (GNETs) are typically managed either expectantly or endoscopically. In contrast, locoregional surgery has been recommended for patients with type III GNETs because of the risk of metastasis. This study aimed to identify predictors of outcome independent of type in a contemporary cohort of GNET patients. METHODS A single-institution retrospective cohort study of 121 patients with a pathologic diagnosis of primary GNET between January 2009 and June 2019 was performed. GNETs were designated as type 1 (n = 74) if atrophic gastritis was present, or as type III (n = 47) in the absence of atrophic gastritis. Demographic, clinical, and histopathologic factors were examined using Kaplan-Meier and multivariable Cox regression to assess the impact of various factors on recurrence and overall survival. RESULTS Median follow-up for the entire cohort was 62.7 months. While there was no difference in OS in patients with different GNET types (p = 0.10), higher tumor grade (p = 0.02) and presence of nodal or distant metastases (p = 0.02) predicted worse survival on multivariable analysis. Among type III GNET patients, those with small (< 0.5 cm), grade 1 lesions ("low-risk") were less likely to develop metastases (0% versus 33%, p < 0.01) and more likely to survive (100% versus 67%, p < 0.01) at 5 years. CONCLUSIONS Size and tumor grade predict recurrence and survival in patients with GNETs irrespective of type. Small, low-grade type III GNETs are associated with minimal risk of progression and may be managed accordingly.
Collapse
Affiliation(s)
- Andrew Hanna
- Department of General Surgery, University of Pennsylvania, Philadelphia, PA, USA.
| | | | - Rebecca Tang
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - David C Metz
- Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Zhaohai Yang
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Ronald DeMatteo
- Department of General Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Douglas L Fraker
- Department of General Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Robert E Roses
- Department of General Surgery, University of Pennsylvania, Philadelphia, PA, USA
| |
Collapse
|
|
37
|
Lorenzo D, Maire F, Hentic O, Prat F, Ruszniewski P, de Mestier L. Endoscopic diagnosis and treatment of neuroendocrine tumors. CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH 2021; 18:201-206. [DOI: 10.1016/j.coemr.2021.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
38
|
Jung SW. Endoscopic Treatment of Gastric and Duodenal Neuroendocrine Tumors: Present and Future. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2020.0055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Gastric and duodenal neuroendocrine tumors (NETs) are not common; however, there is an increase in the incidence due to increased use of endoscopy. Endoscopic treatment has been applied to treat small NET G1 in the stomach and duodenum. For the endoscopic treatment of NETs, it is necessary to evaluate tumor size, depth of invasion, and lymphatic and distant metastasis. This article will review the current knowledge concerning the endoscopic treatment of gastric and duodenal neuroendocrine tumors.
Collapse
|
|
39
|
Hirasawa T, Yamamoto N, Sano T. Is endoscopic resection appropriate for type 3 gastric neuroendocrine tumors? Retrospective multicenter study. Dig Endosc 2021; 33:408-417. [PMID: 32578248 DOI: 10.1111/den.13778] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 06/12/2020] [Accepted: 06/16/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Gastrectomy with lymphadenectomy is recommended for type 3 gastric neuroendocrine tumors (G-NETs). This study aimed to identify the risk factors for lymph node metastasis (LNM) arising from G-NETs to assess the suitability of endoscopic resection (ER). METHODS Nationwide clinicopathological data of patients with type 3 G-NETs who underwent surgery or ER were collected. A single pathologist graded the histological tumor specimens. RESULTS Among 176 cases from 53 institutions, 144 were eligible for analysis (90 NET-G1 and 54 NET-G2 grade, 8-mm median-size tumors). Of these, 63 patients had undergone ER (15 with additional surgeries). Histological data regarding LNM were available for 93 surgical patients. LNM was confirmed in 15 (16%) tumors and was correlated with tumor diameter, invasion depth, and tumor grade. LNM was negative in six tumors ≤5 mm, confined to the mucosa or submucosa, with a grade of G1, and without lymphovascular invasion, but the number of cases was too small to propose ER indications. Among 48 patients treated with ER alone, only one developed recurrence; no mortality was observed at follow-up, although many patients were classified with SM2/NET-G2/tumors >5 mm. This suggests that not all LNMs arising from small G-NETs are fatal. CONCLUSION Gastrectomy with lymphadenectomy for type 3 G-NETs is recommended on the basis of LNM. However, ER for type 3 G-NETs ≤10 mm, confined to the mucosa or submucosa, with a grade of G1 has shown excellent survival outcomes despite the risk of LNM, and therefore, could be an alternative treatment option.
Collapse
Affiliation(s)
- Toshiaki Hirasawa
- Departments of, Department of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Noriko Yamamoto
- Department of, Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Sano
- Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| |
Collapse
|
|
40
|
Andreasi V, Partelli S, Muffatti F, Manzoni MF, Capurso G, Falconi M. Update on gastroenteropancreatic neuroendocrine tumors. Dig Liver Dis 2021; 53:171-182. [PMID: 32912771 DOI: 10.1016/j.dld.2020.08.031] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2020] [Revised: 08/20/2020] [Accepted: 08/21/2020] [Indexed: 02/07/2023]
Abstract
The incidence gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has dramatically risen over the last three decades, probably due to the increased detection of asymptomatic lesions. The diagnostic work-up for patients with suspected GEP-NENs is based on conventional imaging, endoscopy, pathology, and functional imaging, including 68Gallium-DOTATATE PET and 18F-FDG PET. The choice of the best treatment strategy should be based on the evaluation of tumor-related features and patient's characteristics. A conservative management, consisting of active surveillance or endoscopic resection, has been advocated for patients with small, incidentally discovered, nonfunctioning tumors without features of aggressiveness. On the other hand, surgery with lymphadenectomy, also with a minimally invasive approach, represents the gold standard for the curative treatment of localized disease. Moreover, surgical resection plays an important role also in the context of a multimodal treatment strategy for patients with advanced GEP-NENs. Finally, a wide range of medical therapies, comprising somatostatin analogues, peptide receptor radionuclide therapy, target therapies and several chemotherapy regimens, can be offered to patients with advanced GEP-NENs not amenable of surgical resection, according to the biological and molecular features of their disease.
Collapse
Affiliation(s)
- Valentina Andreasi
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy
| | - Francesca Muffatti
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy
| | - Marco F Manzoni
- Endocrinology Unit, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Centre, OSR ENETS Center of Excellence IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational & Clinical Research Center, OSR ENETS Center of Excellence, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
| |
Collapse
|
|
41
|
Andreasi V, Partelli S, Muffatti F, Falconi M. New Surgical Strategies. NEUROENDOCRINE NEOPLASIA MANAGEMENT 2021:113-128. [DOI: 10.1007/978-3-030-72830-4_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
42
|
Ravizza D, Fiori G. Gastric Neuroendocrine Tumors. NEUROENDOCRINE NEOPLASIA MANAGEMENT 2021:179-190. [DOI: 10.1007/978-3-030-72830-4_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
43
|
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.
Collapse
|
|
44
|
Li YL, Qiu XD, Chen J, Zhang Y, Li J, Xu JM, Wang C, Qi ZR, Luo J, Tan HY. Clinicopathological characteristics and prognosis of 77 cases with type 3 gastric neuroendocrine tumours. World J Gastrointest Oncol 2020; 12:1416-1427. [PMID: 33362912 PMCID: PMC7739150 DOI: 10.4251/wjgo.v12.i12.1416] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 09/28/2020] [Accepted: 10/28/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND For the rarity of type 3 gastric neuroendocrine tumours (g-NETs), their clinicopathological characteristics and prognosis are not well illustrated. AIM To describe the clinicopathological features and outcome of type 3 g-NETs in the Chinese population. METHODS Based on the 2019 WHO pathological classification, the clinicopathological characteristics and prognosis of patients with type 3 g-NETs in China were retrospectively analysed. RESULTS A total of 77 patients (55.8% of females) with type 3 g-NETs were analysed, with a median age of 48 years (range: 28-79 years). The tumours were mainly located in the gastric fundus/body (83.1%) and were mostly solitary (83.1%), with a median size of 1.5 cm (0.8-3.5 cm). Of these, there were 37 G1 tumours (48.1%), 31 G2 (40.3%), and 9 G3 (11.7%). Ten (13.0%) and 24 (31.2%) patients had lymph node and distant metastasis, respectively. In addition, type 3 g-NETs were heterogeneous. Compared with G1 NETs, G2 NETs had a higher lymph node metastasis rate, and G3 NETs had a higher distant metastasis rate. G1 and G2 NETs with stage I/II disease (33/68) received endoscopic treatment, and no tumour recurrence or tumour-related death was observed within a median follow-up time of 36 mo. Grade and distant metastasis were identified to be independent risk factors for prognosis in multivariable analysis. CONCLUSION Type 3 g-NETs are obviously heterogeneous, and the updated WHO 2019 pathological classification may be used to effectively evaluate their biological behaviors and prognosis. Also, endoscopic treatment should be considered for small (< 2 cm), low grade, superficial tumours.
Collapse
Affiliation(s)
- Yuan-Liang Li
- Beijing University of Chinese Medicine, Beijing 100029, China
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Xu-Dong Qiu
- Beijing University of Chinese Medicine, Beijing 100029, China
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
| | - Yu Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, Guangdong Province, China
| | - Jie Li
- Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Beijing Cancer Hospital, Beijing 100037, China
| | - Jian-Ming Xu
- Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing 100071, China
| | - Chao Wang
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Zhi-Rong Qi
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jie Luo
- Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Huang-Ying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
| |
Collapse
|
|
45
|
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.
Collapse
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
| |
Collapse
|
|
46
|
Alekberzade AV, Krylov NN, Lipnitskiy EM, Shakhbazov RO, Azari F. [Gastric neuroendocrine tumors]. Khirurgiia (Mosk) 2019:111-120. [PMID: 31825351 DOI: 10.17116/hirurgia2019121111] [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: 12/23/2022]
Abstract
Gastrointestinal neuroendocrine tumors are rare neoplasms. Currently, incidence of gastric neuroendocrine tumors (gNETs) is being significantly increased. There are 3 groups of gNETs: types I, II and III. Each type has important features regarding clinical picture, prognosis and treatment strategy. Type I is the most common (70-80%) and associated with chronic atrophic gastritis including autoimmune gastritis and Helicobacter associated atrophic gastritis. Type II (5-6%) is associated with multiple endocrine neoplasia type I and Zollinger-Ellison syndrome (MEN I - ZES). Both types are characterized by hypergastrinemia and small tumor dimension. These neoplasms are multiple and mostly benign. On the contrary, NETs type III (10-15%) is not associated with hypergastrinemia and represented by single large neoplasms. Tumors are malignant as a rule. Therefore, surgical resection and chemotherapy are preferred for these tumors. Endoscopic surgery followed by observation is acceptable for almost all NETS type I and II. At the same time, this approach is advisable only for small and highly differentiated neoplasms type III.
Collapse
Affiliation(s)
- A V Alekberzade
- Sechenov First Moscow State Medical University, Moscow, Russia
| | - N N Krylov
- Sechenov First Moscow State Medical University, Moscow, Russia
| | - E M Lipnitskiy
- Sechenov First Moscow State Medical University, Moscow, Russia
| | - R O Shakhbazov
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA
| | - F Azari
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia PA, USA
| |
Collapse
|
|
47
|
Felder S, Jann H, Arsenic R, Denecke T, Prasad V, Knappe-Drzikova B, Maasberg S, Wiedenmann B, Pavel M, Pascher A, Pape UF. Gastric neuroendocrine neoplasias: manifestations and comparative outcomes. Endocr Relat Cancer 2019; 26:751-763. [PMID: 31272081 PMCID: PMC6686747 DOI: 10.1530/erc-18-0582] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 07/04/2019] [Indexed: 12/15/2022]
Abstract
Although gastric neuroendocrine neoplasias (gNEN) are an orphan disease, their incidence is rising. The heterogeneous clinical course powers the ongoing discussion of the most appropriate classification system and management. Prognostic relevance of proposed classifications was retrospectively analysed in 142 patients from a single tertiary referral centre. Baseline, management and survival data were acquired for statistical analyses. The distribution according to the clinicopathological typification was gNEN-1 (n = 86/60.6%), gNEN-2 (n = 7/4.9%), gNEN-3 (n = 24/16.9%) and gNEN-4 (n = 25/17.6%), while hypergastrinemia-associated gNEN-1 and -2 were all low-grade tumours (NET-G1/2), formerly termed sporadic gNEN-3 could be subdivided into gNEN-3 with grade 1 or 2 and gNEN-4 with grade 3 (NEC-G3). During follow-up 36 patients died (25%). The mean overall survival (OS) of all gNEN was 14.2 years. The OS differed statistically significant across all subgroups with either classification system. According to UICC 2017 TNM classification, OS differed for early and advanced stages, while WHO grading indicated poorer prognosis for NEC-G3. Cox regression analysis confirmed the independent prognostic validity of either classification system for survival. Particularly careful analysis of the clinical course of gNEN-1 (ECLomas, gastric carcinoids) confirmed their mostly benign, but recurrent and extremely slowly progressive behaviour with low risk of metastasis (7%) and an efficient long-term control by repetitive endoscopic procedures. Our study provides evidence for the validity of current classifications focusing on typing, grading and staging. These are crucial tools for risk stratification, especially to differentiate gNEN-1 as well as sporadic gNET and gNEC (gNEN-3 vs -4).
Collapse
Affiliation(s)
- S Felder
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - H Jann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - R Arsenic
- Institut für Pathologie, Charité – Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - T Denecke
- Klinik für Radiologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - V Prasad
- Klinik für Nuklearmedizin, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Klinik für Nuklearmedizin, Universitätklinikum Ulm, Ulm, Germany
| | - B Knappe-Drzikova
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - S Maasberg
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany
| | - B Wiedenmann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - M Pavel
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Medizinische Klinik 1, Gastroenterologie, Pneumologie und Endokrinologie, Universitätsklinikum der Friedrich-Alexander Universität Erlangen, Erlangen, Germany
| | - A Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uinversitätsklinikum Münster, Münster, Germany
| | - U F Pape
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany
- Correspondence should be addressed to U F Pape:
| |
Collapse
|
|
48
|
Tsoli M, Chatzellis E, Koumarianou A, Kolomodi D, Kaltsas G. Current best practice in the management of neuroendocrine tumors. Ther Adv Endocrinol Metab 2019; 10:2042018818804698. [PMID: 30800264 PMCID: PMC6378464 DOI: 10.1177/2042018818804698] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Accepted: 09/05/2018] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine neoplasms are rare tumors that display marked heterogeneity with varying natural history, biological behavior, response to therapy and prognosis. Their management is complex, particularly as a number of them may be associated with a secretory syndrome and involve a variety of options. A number of factors such as proliferation rate, degree of differentiation, functionality and extent of the disease are mostly utilized to tailor treatment accordingly, ideally in the context of a multidisciplinary team. In addition, a number of relevant scientific societies have published therapeutic guidelines in an attempt to direct and promote evidence-based treatment. Surgery remains the treatment of choice with an intention to cure while it may also be recommended in some cases of metastatic disease and difficult to control secretory syndromes. Long-acting somatostatin analogs constitute the main treatment for the majority of functioning tumors, whereas specific evolving agents such as telotristat may be used for the control of carcinoid syndrome and related sequelae. In patients with advanced disease not amenable to surgical resection, treatment options include locoregional therapies, long-acting somatostatin analogs, molecular targeted agents, radionuclides, chemotherapy and recently immunotherapy, alone or in combination. However, the ideal time of treatment initiation, sequence of administration of different therapies and identification of robust prognostic markers to select the most appropriate treatment for each individual patient still need to be defined.
Collapse
Affiliation(s)
| | - Eleftherios Chatzellis
- First Department of Propaedeutic Internal
Medicine, Laiko General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
| | - Anna Koumarianou
- Fourth Department of Internal Medicine, Attikon
University General Hospital, Athens, Greece
| | - Dionysia Kolomodi
- First Department of Propaedeutic Internal
Medicine, Laiko General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
| | - Gregory Kaltsas
- First Department of Propaedeutic Internal
Medicine, Laiko General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
| |
Collapse
|
|
49
|
Grozinsky-Glasberg S, Alexandraki KI, Angelousi A, Chatzellis E, Sougioultzis S, Kaltsas G. Gastric Carcinoids. Endocrinol Metab Clin North Am 2018; 47:645-660. [PMID: 30098721 DOI: 10.1016/j.ecl.2018.04.013] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastric carcinoids, formally named gastric neuroendocrine neoplasms (NENs), are derived from enterochromaffin-like cells of the stomach and are increasingly diagnosed. A majority are designated as type I (related to autoimmune gastritis) and type II (related to gastrinoma) neoplasms that develop secondary to gastrin hypersecretion. Types I and II gastric carcinoids are mostly small-sized (1-2 cm), multiple, low-malignancy potential lesions mainly confined to the gastric mucosa/submucosa. These lesions have an indolent course and low metastatic potential. In contrast, type III gastric carcinoids are single, larger-sized (>2 cm), non-gastrin-related lesions that infiltrate the muscular layers associated with local and distant metastases.
Collapse
Affiliation(s)
- Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, P.O.B. 12000, Jerusalem 91120, Israel
| | - Krystallenia I Alexandraki
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Anna Angelousi
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Eleftherios Chatzellis
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Stavros Sougioultzis
- Department of Pathophysiology, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Gregory Kaltsas
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece.
| |
Collapse
|
|
50
|
Min BH, Hong M, Lee JH, Rhee PL, Sohn TS, Kim S, Kim KM, Kim JJ. Clinicopathological features and outcome of type 3 gastric neuroendocrine tumours. Br J Surg 2018; 105:1480-1486. [PMID: 29893418 DOI: 10.1002/bjs.10901] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Revised: 03/10/2018] [Accepted: 05/03/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND With the widespread use of endoscopy, small and low-grade type 3 gastric neuroendocrine tumours (NETs) are increasingly being detected. The clinicopathological features, biological behaviour and appropriate treatment strategy for these NETs remain unclear. METHODS Patients with biopsy-proven gastric NET and a normal fasting serum gastrin level were identified from a prospectively maintained database. Clinicopathological features and long-term outcome of local resection for type 3 NETs were reviewed retrospectively and compared according to tumour grade. RESULTS Some 32 patients with type 3 gastric NETs were included (25 patients with NET grade G1, 5 with G2 and 2 with G3). Pathological tumour size was 2·0 cm or less in 30 patients. All tumours were well differentiated, even G3 lesions, and all tumours but one were confined to the submucosal layer. G1 NETs were significantly smaller and had a significantly lower lymphovascular invasion rate than G2 and G3 NETs. Twenty-two patients with a G1 NET without lymphovascular invasion were treated with wedge or endoscopic resection. After a median follow-up of 59 (range 6-102) months, no patient with a G1 NET of 1·5 cm or smaller developed recurrence and one patient with a G1 NET larger than 1·5 cm had recurrence in a perigastric lymph node. Among seven patients with a G2 or G3 NET, two had lymph node metastasis and one had liver metastases. CONCLUSION Low-grade type 3 gastric NET has non-aggressive features and a favourable prognosis. Wedge or endoscopic resection may be a valid option for patients with type 3 gastric G1 NET no larger than 1·5 cm without lymphovascular invasion.
Collapse
Affiliation(s)
- B-H Min
- Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - M Hong
- Department of Pathology and Translational Genomics, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - J H Lee
- Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - P-L Rhee
- Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - T S Sohn
- Department of Surgery, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - S Kim
- Department of Surgery, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - K-M Kim
- Department of Pathology and Translational Genomics, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - J J Kim
- Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|