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1
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Ogata Y, Hatta W, Kanno T, Saito M, Jin X, Asano N, Koike T, Imatani A, Yuan Y, Masamune A. Type 2 and type 3 gastric neuroendocrine tumors have high risk of lymph node metastasis: Systematic review and meta-analysis. Dig Endosc 2025. [PMID: 40170116 DOI: 10.1111/den.15026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 03/05/2025] [Indexed: 04/03/2025]
Abstract
OBJECTIVES Lymph node metastasis (LNM) is crucial in determining treatment strategies for gastric neuroendocrine tumors (gNETs). While type 3 is considered more aggressive than types 1 and 2 within the clinical subtype of gNETs, the supporting data were insufficient, due to their rarity. We aimed to study the prevalence and risk factors associated with LNM in gNETs. METHODS We searched electronic databases from 1990 to 2023 to identify case-control and cohort studies regarding gNETs resected either endoscopically or surgically. The primary outcome measured was the pooled prevalence of LNM in gNETs. Secondary outcomes included categorizing the prevalence of LNM by clinical subtypes and identifying pathological risk factors associated with LNM in gNETs. RESULTS We included 28 studies, involving 1742 patients, among whom 240 had LNM (pooled prevalence rate, 11.8%; 95% confidence interval 7.6-17.9%). The pooled prevalence rates of LNM for type 1, type 2, and type 3 gNETs were 6.0%, 38.5%, and 23.2%, respectively. Type 2 (odds ratio [95% confidence interval] 11.53 [3.46-38.49]) and type 3 (6.88 [3.79-12.49]) gNETs exhibited a higher risk for LNM compared to type 1. Pathological risk factors for LNM included tumor size >10 mm (4.18 [1.91-9.17]), tumor invasion into the muscularis propria or deeper (11.21 [3.50-35.92]), grade 2/grade 3 (5.96 [2.65-13.40]), and lymphovascular invasion (34.50 [6.70-177.51]). CONCLUSION We demonstrated that type 2 gNETs, as well as type 3, had a high risk of LNM. Additionally, four pathological risk factors associated with LNM were identified.
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Affiliation(s)
- Yohei Ogata
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Takeshi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Masahiro Saito
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Xiaoyi Jin
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Naoki Asano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Akira Imatani
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Yuhong Yuan
- Department of Medicine, London Health Science Centre, London, Ontario, Canada
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
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2
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Zi M, Ma Y, Chen J, Pang C, Li X, Yuan L, Liu Z, Yu P. Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis. Cancer Med 2024; 13:e7011. [PMID: 38457192 PMCID: PMC10922030 DOI: 10.1002/cam4.7011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/29/2023] [Accepted: 01/31/2024] [Indexed: 03/09/2024] Open
Abstract
OBJECTIVE This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g-NENs). METHODS A retrospective enrollment of 142 patients diagnosed with g-NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (g-NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). RESULTS The study comprised a total of 142 g-NENs cases, with a male-to-female ratio of approximately 2:1. The 5-year survival rates for g-NEC and g-MiNEN were 26.7% and 35.2%, respectively. Corresponding 5-year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g-NEC/MiNEN showed a significantly worse prognosis compared to g-NET (p < 0.001). g-NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g-NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g-NEC/MiNEN (p = 0.010). CONCLUSION In short, the prognosis of g-NEC/MiNEN was worse than that of g-NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.
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Affiliation(s)
- Mengli Zi
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Yubo Ma
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
- The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhouZhejiangChina
| | - Jinxia Chen
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Chuhong Pang
- Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital)HangzhouZhejiangChina
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Xiao Li
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
- The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhouZhejiangChina
| | - Li Yuan
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract CancerZhejiang Cancer HospitalHangzhouChina
- Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal CancerZhejiang Cancer HospitalHangzhouChina
| | - Zhuo Liu
- Department of Colorectum surgeryZhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
| | - Pengfei Yu
- Department of Gastric surgery, Zhejiang Cancer HospitalHangzhou Institute of Medicine (HIM), Chinese Academy of SciencesHangzhouZhejiangChina
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3
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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.
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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
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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.
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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
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5
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Nassereddine H, Chicaud M, Rebah K, Théou-Anton N, Sautet A, Dermer J, Couvelard A. Pathogenic ATM Variant-Harbouring Well-Differentiated Aggressive Type 1 Gastric Neuroendocrine Tumour with High-grade Features (G3 NET): a New Addition to the Clinical and Pathological Spectrum of Gastric Neuroendocrine Neoplasms. Endocr Pathol 2021; 32:517-523. [PMID: 34019237 DOI: 10.1007/s12022-021-09681-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/11/2021] [Indexed: 12/12/2022]
Abstract
Gastric type 1 neuroendocrine tumours are considered to have low rates of proliferation and a good prognosis. We report here a patient with an aggressive well-differentiated high-grade gastric neuroendocrine tumour (gastric grade 3 NET), in a context of autoimmune gastritis. Consistent with grade 3 disease, the tumour had a Ki-67 proliferation index of 30%. Targeted next-generation sequencing identified variants of four genes, including a pathogenic ATM variant underlying the differentiation and metastatic potential of the tumour. Liver metastasis was diagnosed during follow-up, and the patient died after 6 years, due to disease progression.
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Affiliation(s)
- Hussein Nassereddine
- Département de Pathologie, Hôpital Bichat, AP-HP, 46 Rue Henri Huchard, 75018, Paris, France.
| | - Matthieu Chicaud
- Département de Pathologie, Hôpital Bichat, AP-HP, 46 Rue Henri Huchard, 75018, Paris, France
- Sorbonne Université, Paris, France
| | - Khedidja Rebah
- Département de Génétique, Hôpital Bichat, AP-HP, 46 Rue Henri Huchard, 75018, Paris, France
| | - Nathalie Théou-Anton
- Département de Génétique, Hôpital Bichat, AP-HP, 46 Rue Henri Huchard, 75018, Paris, France
| | | | - Jacques Dermer
- Service de Chirurgie Viscérale Et Cancérologique, Clinique de L'Estrée, 93245, Stains, France
| | - Anne Couvelard
- Département de Pathologie, Hôpital Bichat, AP-HP, 46 Rue Henri Huchard, 75018, Paris, France
- Université de Paris, Paris, France
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6
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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.
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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
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7
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Exarchou K, Howes N, Pritchard DM. Systematic review: management of localised low-grade upper gastrointestinal neuroendocrine tumours. Aliment Pharmacol Ther 2020; 51:1247-1267. [PMID: 32390152 DOI: 10.1111/apt.15765] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 02/24/2020] [Accepted: 04/12/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Neuroendocrine tumours (NETs) of the stomach and duodenum are rare, but are increasing in incidence. Optimal management of localised, low-grade gastric and duodenal NETs remains controversial. AIMS To systematically review recent literature that has evaluated the management of localised low-grade gastric and duodenal NETs. METHODS A systematic literature search was conducted. Articles were screened and eligible articles fully assessed. Additional articles were identified through the included articles' reference lists. RESULTS Several relevant retrospective case series were identified, but there was considerable heterogeneity between studies and they reported a variety of parameters. Type I gastric NETs had an excellent prognosis and conservative management approaches such as endoscopic surveillance/resection were appropriate in most cases. Many type III gastric NETs were low grade and appeared to have a better prognosis than has previously been appreciated. Endoscopic rather than surgical resection was therefore effective in some patients who had small, low-grade tumours. Duodenal NETs were more heterogenous. Endoscopic resection was generally safe and effective in patients who had small, low-grade, nonfunctional, non-ampullary tumours. However, some patients, especially those with larger or ampullary duodenal NETs, required surgical resection. CONCLUSIONS Most type I gastric NETs behave indolently and surgical resection is only rarely indicated. Some type III gastric and duodenal NETs have a worse prognosis, but selected patients who have small, localised, nonfunctional, low-grade tumours are adequately and safely treated by endoscopic resection. Due to the complexity of this area, a multidisciplinary approach to management is strongly recommended.
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Affiliation(s)
- Klaire Exarchou
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Nathan Howes
- Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - David Mark Pritchard
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
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8
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Kim BS, Park YS, Yook JH, Kim BS. Comparison of the prognostic values of the 2010 WHO classification, AJCC 7th edition, and ENETS classification of gastric neuroendocrine tumors. Medicine (Baltimore) 2016; 95:e3977. [PMID: 27472674 PMCID: PMC5265811 DOI: 10.1097/md.0000000000003977] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
The ability of the European Neuroendocrine Tumor Society (ENETS) system, 2010 World Health Organization (WHO) grading system, and American Joint Committee on Cancer (AJCC) staging system to predict survival after gastric neuroendocrine tumor (NET) resection has not yet been validated.We retrospectively evaluated 175 gastric NETs from 1996 to 2014. WHO grade 3 (G3) patients (n = 66) had a lower survival rate than grade 1 (G1) (n = 39) or grade 2 (G2) (n = 13) patients, with similar high survival rates for G1 and G2 patients. G3 patients had a lower survival rate than mixed-type patients (n = 57). Using the AJCC classification, most of the G1/2 NETs (86.6%) were confined to T1/T2, N0 tumor, and stage I/IIa, but the survival rate was not well distributed. In contrast, G3/mixed tumors were well distributed in terms of T, N, stage, and survival. Using the ENETS classification, 64.6% of the tumors were T2 and only 8.6% were T3. In addition, 49.7% were stage IIIb and only 1.9% was IIa, with poor survival distribution.Our findings strongly suggested that the WHO and ENETS classification systems have shown a low prognostic value. The AJCC TNM system showed a low prognostic value for well-differentiated NETs (G1 or G2). In contrast, the AJCC TNM system had a high prognostic value for G3 or mixed tumors.
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Affiliation(s)
- Beom Su Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Soo Park
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hwan Yook
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byung-Sik Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Correspondence: Byung-Sik Kim, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, SongPa-Gu, Seoul 05505, Korea (e-mail: )
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9
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Zou TH, Zheng RH, Gao QY, Kong X, Chen XY, Ge ZZ, Chen YX, Zou XP, Fang JY. Factors affecting occurrence of gastric varioliform lesions: A case-control study. World J Gastroenterol 2016; 22:5228-5236. [PMID: 27298565 PMCID: PMC4893469 DOI: 10.3748/wjg.v22.i22.5228] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Revised: 03/16/2016] [Accepted: 03/30/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the factors influencing the occurrence of gastric varioliform lesions (GVLs) and their possible link with gastric cancer.
METHODS: A 1:1 matched case-control study was performed to retrospectively analyze data from 1638 chronic gastritis patients who had undergone gastroscopy at one of two Chinese hospitals between 2009 and 2014. Patients with GVLs (cases) were compared to those without such lesions (controls). Endoscopic and pathological findings were recorded, along with interview information on Helicobacter pylori (H. pylori) infection, medical, drug and family histories, lifestyle and eating habits. The association between each factor and the occurrence of GVLs was estimated, and then multivariate conditional logistic regression was used to evaluate the independent factors.
RESULTS: The frequency and severity of glandular atrophy, intestinal metaplasia (IM) and low-grade intraepithelial neoplasia were significantly increased in the GVL group (P < 0.01). Overall analysis showed that H. pylori infection [3.051 (2.157, 4.317), P <0.001], allergic respiratory diseases [3.636 (2.183, 6.055), P < 0.001], work-related stress [2.019 (1.568, 2.600), P < 0.001], irregular meals [2.300 (1.462, 3.619), P < 0.001], high intake of spicy food [1.754 (1.227, 2.507), P = 0.002] and high intake of fresh fruit [0.231 (0.101, 0.529), P = 0.001] were significantly correlated with the occurrence of GVLs (positively, except for the latter). Stratified analyses indicated that pickled food consumption in patients over 50 years old [7.224 (2.360, 22.115), P = 0.001] and excessive smoking in men [2.013 (1.282, 3.163), P = 0.002] were also positively correlated, and that, for antral GVLs, vegetable consumption [0.491 (0.311, 0.776), P = 0.002] was negatively correlated.
CONCLUSION: Seven risk factors and two protective factors are determined for GVLs, which were found to be associated with premalignant abnormalities.
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10
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Azakami K, Nishida K, Tanikawa K. [A case of gastric endocrine cell carcinoma which was significantly reduced in size by radiotherapy]. Nihon Ronen Igakkai Zasshi 2016; 53:62-9. [PMID: 26935520 DOI: 10.3143/geriatrics.53.62] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
In 2010, the World Health Organization classified gastric neuroendocrine tumors (NETs) into three types: NET grade (G) 1, NET G2 and neuroendocrine carcinoma (NEC). NECs are associated with a very poor prognosis. The patient was an 84-year-old female who was initially diagnosed by gastrointestinal endoscope with type 3 advanced gastric cancer with stenosis of the gastric cardia. Her overall status and performance status did not allow for operations or intensive chemotherapy. Palliative radiotherapy was performed and resulted in a significant reduction in the size of the tumor as well as the improvement of the obstructive symptoms. She died 9 months after radiotherapy. An autopsy provided a definitive diagnosis of gastric endocrine cell carcinoma, and the effectiveness of radiotherapy was pathologically-confirmed. Palliative radiotherapy may be a useful treatment option for providing symptom relief, especially for old patients with unresectable advanced gastric neuroendocrine carcinoma.
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11
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Liang P, Wang YX, Ren XC, Gao JB. Neuroendocrine carcinoma of the stomach: clinical features and CT findings. Abdom Radiol (NY) 2016; 41:19-24. [PMID: 26830607 DOI: 10.1007/s00261-015-0593-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE The purpose of the study is to investigate the computed tomographic characteristic and clinical findings of gastric neuroendocrine carcinoma (G-NEC) to increase awareness of this disease. METHODS Twenty-two patients with a diagnosis of G-NEC were identified through the PACS of our hospital from August 2010 to November 2014. The clinical data, computed tomography (CT) features, and pathology records were analyzed. RESULTS Among the 22 patients, 21 were male (95.45%), and 1 was female (4.55%). The mean age was 63.5 years old. Positive rates of neuroendocrine markers were 77.28% for chromogranin A staining, 86.36% for synaptophysin staining. All cases were single lesions including 16 (72.73%) in the gastric fundus, 3 (13.64%) in the gastric body and 1 (4.55%) in the gastric angle. Additionally 2 (9.09%) were found in the gastric antrum. Gastric wall was local thickening in 15 cases, and mass formation in 7 cases, with the stenosis and deformation of the adjacent gastric cavity. The long-axis diameter of the lesions ranged from 1.2 to7.4 cm (mean diameter, 2.47 cm), and the long-axis diameter was <2 cm in 12 case, 2-7.4 cm in 10 cases. The radiodensity values of the lesions were homogeneous density in 15 cases ranging from 22 to 47 HU (mean 34 HU). An ulcer with an irregular base and slightly raised borders located in the stomach was seen in 19 cases. The CT images showed homogeneous enhancement in 15 cases and heterogeneous enhancement in 7 cases. Obvious enhancement was seen in two cases, moderate enhancement was seen in sixteen cases, and mildly enhancement was seen in four cases. The peak value occurred in the arterial phase in 5 cases and the peak value was seen in 17 cases in the portal phase. Eleven lesions invaded the gastric serosa, and lymphatic metastasis was observed in 21 cases, 8 of which were combined with liver metastasis. CT images revealed 2 cases of the liver metastasis had obvious enhancement. CONCLUSION The CT features regarding location, incidence rates of ulcer and enhancement pattern described in our findings are common in all malignant gastric tumors. Therefore, the diagnosis of G-NEC must be confirmed with pathological test.
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Affiliation(s)
- Pan Liang
- Department of Radiology, The First Affiliated Hospital, Zhengzhou University, No.1. Eastern Jianshe Road, Zhengzhou, 450052, China
| | - Yi-Xu Wang
- Department of Radiology, The First Affiliated Hospital, Zhengzhou University, No.1. Eastern Jianshe Road, Zhengzhou, 450052, China
| | - Xiu-Chun Ren
- Department of Radiology, The First Affiliated Hospital, Zhengzhou University, No.1. Eastern Jianshe Road, Zhengzhou, 450052, China
| | - Jian-Bo Gao
- Department of Radiology, The First Affiliated Hospital, Zhengzhou University, No.1. Eastern Jianshe Road, Zhengzhou, 450052, China.
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Kim BS, Park YS, Yook JH, Oh ST, Kim BS. Differing Clinical Courses and Prognoses in Patients With Gastric Neuroendocrine Tumors Based on the 2010-WHO Classification Scheme. Medicine (Baltimore) 2015; 94:e1748. [PMID: 26554772 PMCID: PMC4915873 DOI: 10.1097/md.0000000000001748] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 09/10/2015] [Accepted: 09/15/2015] [Indexed: 12/20/2022] Open
Abstract
The aim of this study is to test the prognostic accuracy of the 2010-WHO classification for postsurgery survival in nonmetastatic gastric neuroendocrine tumor (NET) cases. Whether the 2010-WHO classification of NETs can predict relapse after surgical resection has not yet been established.We selected 175 nonmetastatic gastric NET patients at Asan Medical Center, Seoul, Korea between 1996 and 2013. All tumors were classified using the WHO-2010 scheme.Among 175 patients with gastric NETs, we diagnosed 39 cases as WHO grade 1, 13 cases as grade 2, 66 cases as grade 3 (neuroendocrine carcinomas; NECs), and 57 cases as mixed with adenocarcinoma. Patients with grade 3 had a lower relapse-free survival (RFS) and overall survival (OS) than those with WHO grade 1/2 and had a lower OS than patients with mixed type tumors. Patients with grade 1/2 had a better OS than patients with mixed type. There was no significant difference in RFS and OS between small and large cell type lesions. Among WHO grade 1/2 patients with ≤1 cm sized lesions, none exhibited lympho-vascular, perineural, mucosal, or submucosal invasion, and we detected no lymph node metastases or recurrences.Our findings strongly suggest that WHO grade 3 behaves more aggressively than adenocarcinoma. Additionally, the survival of cases with large and small cell NEC was similar. Among WHO grade 1/2 patients who had ≤1 cm lesions, none exhibited lympho-vascular, perineural, mucosal, or submucosal invasion and all could be treated by endoscopic resection or minimally invasive surgery without node dissection.
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Affiliation(s)
- Beom Su Kim
- From the Department of Surgery (BSK, JHY, STO, BSK); and Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (YSP)
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Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review. Diagnostics (Basel) 2015; 5:119-76. [PMID: 26854147 PMCID: PMC4665594 DOI: 10.3390/diagnostics5020119] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 03/24/2015] [Accepted: 03/26/2015] [Indexed: 02/07/2023] Open
Abstract
To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4–16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning surgery are often undecided and second-line chemotherapy is not yet established. After an analysis of over 2600 articles, we can conclude that there is indeed more empirical literature concerning GEP-NECs available than previously assumed. This unique review is based on 333 selected articles and contains detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation, diagnosis, treatment and survival are presented. Finally, key points are discussed with directions for future research priorities.
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Endo S, Yamada T, Nakagawa T, Chihara T, Yamauchi A, Nishikawa K, Nishijima J. Esophageal endocrine cell carcinoma: a report of eight cases and a review of the literature. Esophagus 2014; 11:267-272. [DOI: 10.1007/s10388-013-0404-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/29/2023]
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Xu HY, Zhang ZY, Ren F, Tang L, Zhang FC. Clinicopathological characteristics and prognostic factors of gastric neuroendocrine carcinoma. Shijie Huaren Xiaohua Zazhi 2014; 22:3291-3299. [DOI: 10.11569/wcjd.v22.i22.3291] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the clinical characteristics and prognostic factors of gastric neuroendocrine carcinoma (GNEC).
METHODS: The clinical data for 50 GNEC patients treated at our hospital between November 1, 2007 and March 31, 2014 were reviewed and analyzed retrospectively. Kaplan-Meier survival curves were plotted, and log-rank tests and Cox proportional hazards analysis were used for univariate and multivariate comparisons of overall survival (OS).
RESULTS: There were 44 neuroendocrine carcinoma (NEC) (G3) and 6 mixed adenoneuroendocrine carcinoma (MANEC) (G2-3) patients enrolled in this study. Among them, 39 were male and 11 were female, with a median age of 61.32±10.48 years. At presentation, 6 (12.0%) cases were diagnosed with stage Ⅱ, and the percentages of stage Ⅲ and Ⅳ patients was 68.0% and 20.0%, respectively. All of the cases received radical surgery for the primary and metastatic masses. 36 (72.0%) cases had lymph node metastasis and intravascular tumor thrombi were found in 17 (34.0%) cases. The percentage of patients receiving chemotherapy was 50.0% (25/50). The follow-up duration was 1 to 50 mo. 15 cases developed relapse and 18 patients died. Univariate analysis revealed that the ratio of neutrophils to lymphocytes (NLR), Ki67 and chemotherapy were significant prognostic factors (P < 0.05). Cox regression analysis showed that Ki67 was an independent prognostic factor.
CONCLUSION: GNEC is a relatively uncommon and highly aggressive malignancy, and Ki67 is an important independent prognostic factor.
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Chen Z, Xiao HE, Ramchandra P, Huang HJ. Imaging and pathological features of primary hepatic neuroendocrine carcinoma: An analysis of nine cases and review of the literature. Oncol Lett 2014; 7:956-962. [PMID: 24944650 PMCID: PMC3961293 DOI: 10.3892/ol.2014.1844] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2013] [Accepted: 11/29/2013] [Indexed: 02/07/2023] Open
Abstract
The present study aimed to analyze the imaging features and pathological basis of primary hepatic neuroendocrine carcinoma (PHNEC). A retrospective analysis of the imaging and pathological features of nine PHNEC cases was carried out at The Second Xiangya Hospital of Central South University (Changsha, China). The nine patients were subjected to dynamic contrast-enhanced computed tomography (CT) scanning of the liver and pathological diagnosis of the tissue samples. In addition, two patients were subjected to magnetic resonance imaging (MRI). CT scanning revealed the presence of single or multiple masses in the liver with a maximum diameter of 1–10 cm. These hepatic masses were of low density as showed by plain CT. These masses showed uneven or annular enhancement at their margins in the arterial phase. The venous portal phase showed consistent or declined enhancement and the delayed phase showed light enhancement in these masses. In addition, multiple intrahepatic nodules with long T1 and T2 signal intensities and obvious enhancement were observed by MRI in one patient, while intrahepatic lesions with moderate length T2 signal intensities and light enhancement not visible on the T1 image were observed in another patient. Pathological analysis revealed that the tumor cells exhibited morphological diversity. Immunohistochemical staining revealed that the tumor cells were chromogranin A- and synaptophysin-positive, and carcinoembryonic antigen-, hepatocytic antigen- and α-fetoprotein-negative. Imaging methods, including CT and MRI, are useful for the diagnosis of PHNEC; however, pathological examination is required for a final, definite diagnosis.
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Affiliation(s)
- Zhu Chen
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Hua-En Xiao
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Paudel Ramchandra
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Hai-Jiang Huang
- Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
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