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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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Shinozaki S, Osawa H, Miura Y, Nomoto H, Sakamoto H, Hayashi Y, Yano T, Despott EJ, Yamamoto H. Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy. DEN OPEN 2025; 5:e400. [PMID: 38919514 PMCID: PMC11196240 DOI: 10.1002/deo2.400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 05/27/2024] [Accepted: 06/03/2024] [Indexed: 06/27/2024]
Abstract
Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.
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Affiliation(s)
- Satoshi Shinozaki
- Shinozaki Medical ClinicTochigiJapan
- Department of MedicineDivision of GastroenterologyJichi Medical UniversityTochigiJapan
| | - Hiroyuki Osawa
- Department of MedicineDivision of GastroenterologyJichi Medical UniversityTochigiJapan
| | - Yoshimasa Miura
- Department of MedicineDivision of GastroenterologyJichi Medical UniversityTochigiJapan
- Department of MedicineDivision of Gastroenterology and HepatologyNihon University School of MedicineTokyoJapan
| | - Hiroaki Nomoto
- Department of MedicineDivision of GastroenterologyJichi Medical UniversityTochigiJapan
| | - Hirotsugu Sakamoto
- Department of MedicineDivision of GastroenterologyJichi Medical UniversityTochigiJapan
| | - Yoshikazu Hayashi
- Department of MedicineDivision of GastroenterologyJichi Medical UniversityTochigiJapan
| | - Tomonori Yano
- Department of MedicineDivision of GastroenterologyJichi Medical UniversityTochigiJapan
| | - Edward J. Despott
- Royal Free Unit for EndoscopyThe Royal Free Hospital and UCL Institute for Liver and Digestive HealthLondonUK
| | - Hironori Yamamoto
- Department of MedicineDivision of GastroenterologyJichi Medical UniversityTochigiJapan
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Matsueda K, Uedo N, Kitamura M, Kanesaka T, Morita M, Shichijo S, Maekawa A, Takeuchi Y, Higashino K, Michida T, Ishihara R, Kawano S, Otsuka M. Endoscopic features of gastric neuroendocrine tumors. DEN OPEN 2025; 5:e70088. [PMID: 40017512 PMCID: PMC11864922 DOI: 10.1002/deo2.70088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 01/10/2025] [Accepted: 02/14/2025] [Indexed: 03/01/2025]
Abstract
OBJECTIVES The endoscopic features of gastric neuroendocrine tumors (G-NETs) remain unclarified. The present study investigated the endoscopic features of G-NETs in relation to the clinicopathological findings. METHODS This retrospective study analyzed consecutive patients with G-NETs who received endoscopic or surgical treatment between January 2005 and December 2023. The endoscopic and clinicopathological findings of the lesions were analyzed to provide diagnostic information. RESULTS Among 29 patients, the characteristic endoscopic findings of G-NETs on white-light images were reddish color (66%), dilated vessels (83%), submucosal tumor-like marginal elevation (59%), and central depression (48%). The gross appearance of G-NETs was classified into two macroscopic subtypes: reddish polypoid lesions (n = 17) and submucosal tumor-like lesions (n = 9). Magnifying narrow-band imaging endoscopy revealed an absent microsurface pattern plus an irregular microvascular pattern in all cases of reddish polypoid lesions with central depressions (100%, 9/9). The findings of a reddish polypoid lesion and an absent microsurface pattern plus an irregular microvascular pattern corresponded to the subepithelial NET component close to the non-neoplastic surface epithelium. Additionally, reddish polypoid lesions were significantly more frequent in type 1 G-NETs than in type 3 G-NETs (80% vs. 11%, p < 0.001), while submucosal tumor-like lesions were significantly more frequent in type 3 G-NETs than in type 1 G-NETs (78% vs. 10%, p < 0.001). CONCLUSIONS These endoscopic features should increase the index of suspicion and help clinicians to correctly diagnose G-NETs through the pathological examination of biopsy specimens.
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Affiliation(s)
- Katsunori Matsueda
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
- Department of Gastroenterology and HepatologyOkayama University HospitalOkayamaJapan
| | - Noriya Uedo
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Masanori Kitamura
- Department of Diagnostic Pathology and CytologyOsaka International Cancer InstituteOsakaJapan
| | - Takashi Kanesaka
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Muneshin Morita
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Satoki Shichijo
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Akira Maekawa
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Yoji Takeuchi
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
- Department of Gastroenterology and HepatologyGunma University Graduate School of MedicineGunmaJapan
| | - Koji Higashino
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Tomoki Michida
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Ryu Ishihara
- Department of Gastrointestinal OncologyOsaka International Cancer InstituteOsakaJapan
| | - Seiji Kawano
- Department of Gastroenterology and HepatologyOkayama University HospitalOkayamaJapan
| | - Motoyuki Otsuka
- Department of Gastroenterology and HepatologyOkayama University HospitalOkayamaJapan
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Castellana C, Eusebi LH, Dajti E, Iascone V, Vestito A, Fusaroli P, Fuccio L, D’Errico A, Zagari RM. Autoimmune Atrophic Gastritis: A Clinical Review. Cancers (Basel) 2024; 16:1310. [PMID: 38610988 PMCID: PMC11010983 DOI: 10.3390/cancers16071310] [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: 02/16/2024] [Revised: 03/22/2024] [Accepted: 03/26/2024] [Indexed: 04/14/2024] Open
Abstract
Autoimmune atrophic gastritis (AAG) is a chronic condition characterized by the presence of atrophy in the oxyntic mucosa due to anti-parietal cell antibodies. This review provides a comprehensive and up-to-date overview of autoimmune atrophic gastritis, reporting recent evidence on epidemiology, pathogenesis, diagnosis, clinical presentation, risk of malignancies, and management. The prevalence of AAG has been estimated at between 0.3% and 2.7% in the general population. The diagnosis of AAG is based on a combination of the serologic profile and the histological examination of gastric biopsies. Patients with AAG are often asymptomatic but can also have dyspeptic or reflux symptoms. The atrophy of the oxyntic mucosa leads to iron and vitamin B12 malabsorption, which may result in anemia and neurological affections. Autoimmune atrophic gastritis is associated with an increased risk of type I neuroendocrine tumors (NETs) and gastric cancer, with an incidence rate of 2.8% and 0.5% per person/year, respectively. Management is directed to reinstate vitamins and iron and to prevent malignancies with endoscopic surveillance. In conclusion, atrophic autoimmune gastritis is an infrequent condition, often asymptomatic and misdiagnosed, that requires an early diagnosis for appropriate vitamin supplementation and endoscopic follow-up for the early diagnosis of NETs and gastric cancer.
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Affiliation(s)
- Chiara Castellana
- Department of Medical Sciences and Surgery, University of Bologna, 40138 Bologna, Italy; (C.C.); (L.H.E.); (E.D.); (V.I.); (L.F.); (A.D.)
- Gastroenterology Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Leonardo Henry Eusebi
- Department of Medical Sciences and Surgery, University of Bologna, 40138 Bologna, Italy; (C.C.); (L.H.E.); (E.D.); (V.I.); (L.F.); (A.D.)
- Gastroenterology Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Elton Dajti
- Department of Medical Sciences and Surgery, University of Bologna, 40138 Bologna, Italy; (C.C.); (L.H.E.); (E.D.); (V.I.); (L.F.); (A.D.)
| | - Veronica Iascone
- Department of Medical Sciences and Surgery, University of Bologna, 40138 Bologna, Italy; (C.C.); (L.H.E.); (E.D.); (V.I.); (L.F.); (A.D.)
- Gastro-Esophageal Organic Diseases Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Amanda Vestito
- Gastroenterology Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Pietro Fusaroli
- Department of Medical Sciences and Surgery, University of Bologna, 40138 Bologna, Italy; (C.C.); (L.H.E.); (E.D.); (V.I.); (L.F.); (A.D.)
- Gastroenterology Unit, Hospital of Imola, 40026 Imola, Italy
| | - Lorenzo Fuccio
- Department of Medical Sciences and Surgery, University of Bologna, 40138 Bologna, Italy; (C.C.); (L.H.E.); (E.D.); (V.I.); (L.F.); (A.D.)
- Gastroenterology Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Antonietta D’Errico
- Department of Medical Sciences and Surgery, University of Bologna, 40138 Bologna, Italy; (C.C.); (L.H.E.); (E.D.); (V.I.); (L.F.); (A.D.)
- Pathology Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Rocco Maurizio Zagari
- Department of Medical Sciences and Surgery, University of Bologna, 40138 Bologna, Italy; (C.C.); (L.H.E.); (E.D.); (V.I.); (L.F.); (A.D.)
- Gastro-Esophageal Organic Diseases Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
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Zhou Y, Li JW, Uedo N. Multimodal management of foregut neuroendocrine neoplasms. Best Pract Res Clin Gastroenterol 2024; 68:101889. [PMID: 38522885 DOI: 10.1016/j.bpg.2024.101889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Accepted: 01/30/2024] [Indexed: 03/26/2024]
Abstract
The foregut, which includes the esophagus, stomach and duodenum, represents one of the most common sites for neuroendocrine neoplasms. These are highly heterogenous with different risk of progression depending on location, cell-type of origin, size, grade and other factors. Various endoscopic and imaging modalities exist to inform therapeutic decision-making, which may be in the form of surgical or endoscopic resection and medical therapy depending on the extent of the disease after diagnostic evaluation. This narrative review aims to explore the literature on the multimodal management of such foregut neuroendocrine neoplasms.
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Affiliation(s)
- Yichan Zhou
- Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, China
| | - James Weiquan Li
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Japan; Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore Health Services, Singapore
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Japan.
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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.
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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.
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7
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Kim Y, Ahn B, Choi KD, Kim BS, Yook JH, Lee GH, Hong SM, Lee JH. Gastric Neuroendocrine Tumors According to the 2019 World Health Organization Grading System: A Single-Center, Retrospective Study. Gut Liver 2023; 17:863-873. [PMID: 36588525 PMCID: PMC10651375 DOI: 10.5009/gnl220175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 07/19/2022] [Accepted: 08/18/2022] [Indexed: 01/03/2023] Open
Abstract
Background/Aims Although gastric neuroendocrine tumors (NETs) are uncommon neoplasms, their prevalence is increasing. The clinical importance of the World Health Organization (WHO) classification of gastric NETs, compared with NETs in other organs, has been underestimated. This study aimed to systematically evaluate the clinical and pathologic characteristics of gastric NETs based on the 2019 WHO classification and to assess the survival outcomes of patients from a single-center with a long-term follow-up. Methods The medical records of 427 patients with gastric NETs who underwent endoscopic or surgical resection between January 2000 and March 2020 were retrospectively reviewed. All specimens were reclassified according to the 2019 WHO classification. The clinicopathologic characteristics, treatment, and oncologic outcomes of 139 gastric NETs were analyzed. Results The patients' median age was 53.0 years (interquartile range [IQR], 46.0 to 63.0 years). The median follow-up period was 36.0 months (IQR, 15.0 to 63.0 months). Of the patients, 92, 44, and 3 had grades 1, 2, and 3 NETs, respectively. The mean tumor size significantly increased as the tumor grade increased (p=0.025). Patients with grades 2 and 3 gastric NETs more frequently had lymphovascular invasion (29.8% vs 10.9%, p=0.005) and deeper tissue invasion (8.5% vs 0%, p=0.012) than those with grade 1 tumors. The overall disease-specific survival rate was 100%. Two patients with grades 2-3 gastric NETs experienced extragastric recurrence. Conclusions Although gastric NETs have an excellent prognosis, grade 2 or grade 3 gastric NETs are associated with a larger size, deeper invasion, and extragastric recurrence, which require active treatment.
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Affiliation(s)
- Yuri Kim
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Bokyung Ahn
- Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Don Choi
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Beom-Su Kim
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Hwan Yook
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gin Hyug Lee
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Mo Hong
- Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hoon Lee
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Namikawa K, Kamada T, Fujisaki J, Sato Y, Murao T, Chiba T, Kaizaki Y, Ishido K, Ihara Y, Kurahara K, Suga T, Suzuki H, Ito M, Hirakawa K, Maruyama Y, Gotoda T, Hosokawa O, Koike T, Mabe K, Yao T, Inui K, Iishi H, Ogata H, Furuta T, Haruma K. Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort. Dig Endosc 2023; 35:757-766. [PMID: 36721901 DOI: 10.1111/den.14529] [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: 09/25/2022] [Accepted: 01/29/2023] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.
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Affiliation(s)
- Ken Namikawa
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Tomoari Kamada
- Department of Health Care Medicine, Kawasaki Medical School, Okayama, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Junko Fujisaki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Yuichi Sato
- Department of Gastroenterology, Niigata University Graduate School of Medicine and Dental Sciences, Niigata, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Takahisa Murao
- Department of Health Care Medicine, Kawasaki Medical School, Okayama, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Tsutomu Chiba
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Yasuharu Kaizaki
- Department of Pathology, Fukui Prefectural Hospital, Fukui, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Kenji Ishido
- Department of Gastroenterology, Kitasato University School of Medicine, Kanagawa, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Yutaro Ihara
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Koichi Kurahara
- Division of Gastroenterology, Matsuyama Red Cross Hospital, Ehime, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Tomoaki Suga
- Endoscopic Examination Center, Shinshu University, Nagano, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Haruhisa Suzuki
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Masanori Ito
- Department of General Internal Medicine, Hiroshima University Hospital, Hiroshima, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Katsuya Hirakawa
- Division of Gastroenterology, Fukuoka Red Cross Hospital, Fukuoka, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Yasuhiko Maruyama
- Division of Gastroenterology, Fujieda Municipal General Hospital, Shizuoka, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Takuji Gotoda
- Department of Gastroenterology, Nihon University Hospital, Tokyo, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Osamu Hosokawa
- Department of Surgery, Yokohama Sakae Kyosai Hospital, Kanagawa, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Tomohiro Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Katsuhiro Mabe
- Junpukai Health Maintenance Center - Kurashiki, Okayama, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Kazuo Inui
- Department of Gastroenterology Yamashita Hospital, Aichi, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Hiroyasu Iishi
- Department of Gastroenterology, Itami City Hospital, Hyogo, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Haruhiko Ogata
- Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Tokyo, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Shizuoka, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
| | - Ken Haruma
- Division of Gastroenterology, Department of Internal Medicine 2, Kawasaki Medical School, Okayama, Japan
- Research Group on the Treatment Guidelines for Gastric Carcinoids Associated with Autoimmune Gastritis in Japan, Tokyo, Japan
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9
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Funatsu N, Hara K, Takagi M, Onodera A, Ueno K, Endo K, Cho H. Robotically assisted total gastrectomy for lymphadenopathy after long-term follow-up for multiple type 1 gastric neuroendocrine tumor (NET): a case report. Surg Case Rep 2023; 9:142. [PMID: 37556088 PMCID: PMC10412512 DOI: 10.1186/s40792-023-01725-5] [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: 04/28/2023] [Accepted: 08/01/2023] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND Type 1 gastric neuroendrine tumor (NET) is usually associated with chronic atrophic gastritis and forms multiple lesions. While most cases of type 1 gastric NET are generally slowly growing, some develop regional lymph node metastases even after long-term dormancy. CASE PRESENTATION A 73-year-old male patient with a 32-year history of multiple gastric NET was being followed-up at the study center after endoscopic submucosal dissection (ESD) of a large gastric NET. A blood examination revealed high serum gastrin (> 3000 pg/ml). An endoscopic examination found atrophic mucosa and multiple, elevated lesions in the upper to lower stomach body. Computed tomography (CT) revealed regional lymphadenopathy in the greater omentum along the gastroepiploic artery. Robotically assisted total gastrectomy was performed with D2 lymphadenectomy and Roux-en-Y reconstruction. Pathological analysis revealed a large number of gastric NET (grade 1) with a maximum size of 4.5 mm invading the submucosal layer. A single lymph node metastasis was also detected pathologically at station #4d. The postoperative course was uneventful, and serum gastrin normalized postoperatively. At postoperative year 3, the patient has been doing well without any recurrences. CONCLUSIONS The present case of multiple gastric NET with a single regional lymph node metastasis at year 32 of follow-up was successfully treated with a robotically assisted total gastrectomy.
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Affiliation(s)
- Nozomi Funatsu
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan
| | - Kentaro Hara
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan.
| | - Maki Takagi
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan
| | - Atsushi Onodera
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan
| | - Kohdai Ueno
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan
| | - Kazuya Endo
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan
| | - Haruhiko Cho
- Department of Gastric Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-Ku, Tokyo, 113-8677, Japan
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10
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Chronic Treatment with Somatostatin Analogues in Recurrent Type 1 Gastric Neuroendocrine Tumors. Biomedicines 2023; 11:biomedicines11030872. [PMID: 36979851 PMCID: PMC10045480 DOI: 10.3390/biomedicines11030872] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/14/2023] Open
Abstract
Background: Type 1 gastric neuroendocrine tumors (GC-1) represent an uncommon subtype of neoplasms. Endoscopic resection has been proposed as the treatment of choice; active surveillance may be performed in those smaller than 1 cm, while gastric surgery may be performed for those with frequent recurrences. The antiproliferative effect of somatostatin analogues (SSA) is well known, and their action on GC-1s has been postulated as a chronic treatment to reduce recurrence. Methods: A two-centered, retrospective, observational study that included nine patients (55.6% women) diagnosed with GC-1, receiving long-term treatment with SSA, with a median follow-up from baseline of 22 months, was undertaken. Endoscopic follow-up, extension study, and analytical values of chromogranin A (Cg A) and gastrin were collected. Results: In total, 88.9% of patients presented partial or complete response. Treatment with SSA was the only independent factor with a trend to prevent tumor recurrence (Odds Ratio 0.054; p = 0.005). A nonsignificant tendency toward a decrease in CgA and gastrin was observed; lack of significance was probably related to concomitant treatment with proton pump inhibitors in some patients. Conclusions: Chronic treatment with SSA is a feasible option for recurrent GC-1s that are difficult to manage using endoscopy or gastrectomy. Randomized clinical trials to provide more scientific evidence are still needed.
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11
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Kamada T, Watanabe H, Furuta T, Terao S, Maruyama Y, Kawachi H, Kushima R, Chiba T, Haruma K. Diagnostic criteria and endoscopic and histological findings of autoimmune gastritis in Japan. J Gastroenterol 2023; 58:185-195. [PMID: 36855000 PMCID: PMC9998601 DOI: 10.1007/s00535-022-01954-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 12/30/2022] [Indexed: 03/02/2023]
Abstract
The Japanese diagnostic criteria for autoimmune gastritis (AIG) were established by the "Study Group on the establishment of diagnostic criteria for type A gastritis," which is related to a workshop associated with the Japan Gastroenterological Endoscopy Society (JGES) and the Committee of AIG Research Group (CARP). The criteria were set as follows: the cases of confirmed diagnosis are patients in whom either the endoscopic or histological findings, or both, meet the requirements for AIG and who are confirmed to be positive for gastric autoantibodies (either anti-parietal cell or anti-intrinsic factor antibodies, or both). The presentation of endoscopic findings of early-stage AIG in the diagnostic criteria was withheld owing to the need for further accumulation and characterization of endoscopic clinical data. Therefore, diagnosis of early-stage AIG only requires histological confirmation and gastric autoantibody positivity. Suspected cases are patients in whom either the endoscopic or histological findings, or both, meet only the requirements for AIG. Histological findings only meet the requirements for early stage. AIG has been underdiagnosed in the past, but our study group's newly proposed diagnostic criteria will enable a more accurate and early diagnosis of AIG. The criteria can be used to stratify patients into various high-risk groups for gastric tumors and pernicious anemia. They would allow the establishment of an appropriate surveillance system in the coming years. Nevertheless, issues such as establishing the endoscopic findings of early-stage AIG and obtaining Japanese insurance coverage for gastric autoantibody tests require attention.
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Affiliation(s)
- Tomoari Kamada
- Department of Health Care Medicine, Kawasaki Medical School General Medical Center, 2-6-1, Nakasange, Kita-Ku, Okayama, 700-8505, Japan.
| | | | - Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan
| | - Shuichi Terao
- Department of Gastroenterology, Kakogawa Central City Hospital, Kakogawa, Japan
| | - Yasuhiko Maruyama
- Department of Gastroenterology, Fujieda Municipal General Hospital, Fujieda, Japan
| | - Hiroshi Kawachi
- Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Otsu, Japan
| | | | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School, Kurashiki, Japan
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12
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Gabos G, Nădășan V, Nădășan I, Petruț M, Bernatchi I, Bălășescu M, Nicolau C. Clinical characteristics and endoscopic findings in autoimmune gastritis – A retrospective study. ACTA MARISIENSIS - SERIA MEDICA 2023; 69:61-67. [DOI: 10.2478/amma-2023-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Abstract
Objectives: Autoimmune gastritis (AG) is a rare condition that increases the risk of developing stomach adenocarcinomas or carcinoid tumours. The objectives of the present research were to summarise the clinical traits of AG patients, together with gastroscopic and histopatho-logic findings, demographic data, and hematologic characteristics.
Patients and methods: A medical centre assessed 58 AG patients from January 2019 to December 2022.
Results: The majority of the patients were female (73.7%), and the mean age of the participants at the time of the diagnosis was 57.7 ± 12.1 years. We identified pernicious anaemia (54.4%), iron deficiency anaemia (21.1%), as well as autoimmune disorders (96.5%). Though 78.9% of patients reported having gastrointestinal symptoms, 69% presented exclusively upper gastrointestinal symptoms, 17% only had lower, and 14% had concurrent upper and lower gastrointestinal symptoms. All 58 AG patients were examined for associated gastric lesions, although abnormal injuries were detected in only 22 of them. One patient (1.8%) had adenocarcinoma, while five patients (8.8%) had type 1 neuroendocrine tumours (NET). In addition, hyperplastic polyps were found in 16 (28.1%) individuals.
Conclusions: Other autoimmune diseases were present with AG, which showed a female predominance. Clinicians should give AG more significant thought by allowing access to interdisciplinary teams.
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13
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Starkov YG, Dzhantukhanova SV, Zamolodchikov RD, Zvereva AA, Glotov AV. [Difficulties in diagnosis of neuroendocrine tumors of the gastrointestinal tract]. Khirurgiia (Mosk) 2023:70-76. [PMID: 37850898 DOI: 10.17116/hirurgia202304170] [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] [Indexed: 10/19/2023]
Abstract
We present diagnosis and complex minimally invasive surgical treatment of a patient with long-standing neuroendocrine tumor of the upper gastrointestinal tract. We followed-up a 50-year-old female patient after endoscopic resection of polypoid neoplasm of the stomach for 2 non-organ retroperitoneal neoplasms in the area of hepatogastric ligament. After a comprehensive examination and minimally invasive surgery including laparoscopic resection of retroperitoneal neoplasms, immunohistochemical examination, PET-CT and targeted endoscopic ultrasound of the stomach, we diagnosed a highly differentiated gastric neuroendocrine tumor with metastases into lymph nodes of hepatogastric ligament. Combination of endoscopic and morphological diagnosis with rigorous histological examination of specimen provided correct diagnosis and reasonable strategy of aggressive minimally invasive surgical treatment.
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Affiliation(s)
- Yu G Starkov
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
| | | | - R D Zamolodchikov
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
| | - A A Zvereva
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
| | - A V Glotov
- Vishnevsky National Medical Research Center of Surgery, Moscow, Russia
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14
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Abe Y, Hatta W, Asonuma S, Koike T, Abe H, Ogata Y, Saito M, Jin X, Kanno T, Uno K, Asano N, Imatani A, Fujishima F, Sasano H, Masamune A. Parietal Cell Dysfunction: A Rare Cause of Gastric Neuroendocrine Neoplasm with Achlorhydria and Extreme Hypergastrinemia. Intern Med 2022; 61:2441-2448. [PMID: 35110476 PMCID: PMC9449610 DOI: 10.2169/internalmedicine.8253-21] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 11/04/2021] [Indexed: 11/16/2022] Open
Abstract
A 69-year-old woman with multiple neuroendocrine neoplasms (NENs) was referred to our hospital. Although she had extreme hypergastrinemia (11,675 pg/mL), no findings that indicated types I to III gastric NENs were found. Although gastric corpus atrophy was suspected on conventional white-light imaging, findings on magnifying endoscopy with narrow-band imaging indicated no severe atrophy. A biopsy from the background fundic gland mucosa revealed no atrophic changes, parietal cells with vacuolated cytoplasm and negative findings for H+K+-ATPase. Thus, this case was diagnosed as multiple NENs with parietal cell dysfunction. Neither progression nor metastasis has been confirmed during two-year follow-up.
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Affiliation(s)
- Yasuaki Abe
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Sho Asonuma
- Department of Gastroenterology, South Miyagi Medical Center, Japan
| | - Tomoyuki Koike
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Hiroko Abe
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Yohei Ogata
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Masahiro Saito
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Xiaoyi Jin
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Takeshi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Kaname Uno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Naoki Asano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Akira Imatani
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | - Fumiyoshi Fujishima
- Department of Pathology, Tohoku University Graduate School of Medicine, Japan
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
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15
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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.
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16
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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.
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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
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17
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Kamada T, Maruyama Y, Monobe Y, Haruma K. Endoscopic features and clinical importance of autoimmune gastritis. Dig Endosc 2022; 34:700-713. [PMID: 34674318 DOI: 10.1111/den.14175] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 10/19/2021] [Accepted: 10/19/2021] [Indexed: 12/13/2022]
Abstract
Autoimmune gastritis (AIG) is a special type of chronic gastritis characterized by autoimmune disorders caused by cellular immunity, resulting in the destruction of parietal cells and production of antiparietal cell antibodies. Endoscopic findings of AIG are mainly characterized by corpus-dominant advanced atrophy. The antral area is generally considered to have no or mild atrophy; however, there are cases wherein the gastric mucosa is red or faded due to past infection with Helicobacter pylori or bile reflux. Currently, there are no diagnostic criteria for AIG in Japan, and it is important to make a diagnosis based on the presence of gastric autoantibodies and characteristic endoscopic and histological findings. AIG is associated with gastric cancer, neuroendocrine tumors (NETs), and other autoimmune diseases, such as thyroid diseases, anemia, and neurological symptoms due to impaired absorption of iron and vitamin B12 , and thus requires systemic treatment. The significance of diagnosing AIG is to include patients as a high-risk group for the development of gastric cancer and gastric NETs, provide an opportunity to detect autoimmune endocrine diseases, and initiate therapeutic intervention before anemia and neurological symptoms develop. It is important to pay close attention to the occurrence of AIG comorbidities not only at the time of AIG diagnosis but also during follow-up after detection.
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Affiliation(s)
- Tomoari Kamada
- Department of, Health Care Medicine, Kawasaki Medical School, Okayama, Japan
| | - Yasuhiko Maruyama
- Department of Gastroenterology, Fujieda Municipal General Hospital, Shizuoka, Japan
| | - Yasumasa Monobe
- Department of, Pathology, Kawasaki Medical School, Okayama, Japan
| | - Ken Haruma
- Department of, General Internal Medicine 2, Kawasaki Medical School, Okayama, Japan
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18
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Jeong JH, Lee SY, Han HS. Gastric Corpus Hypertrophy with a Bleeding Hyperplastic Polyp in a Helicobacter pylori-naive Subject After Long-term Proton Pump Inhibitor Use. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2022. [DOI: 10.7704/kjhugr.2021.0062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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19
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Cai Y, Liu Z, Jiang L, Ma D, Zhou Z, Ju H, Zhu Y. Patterns of Lymph Node Metastasis and Optimal Surgical Strategy in Small (≤20 mm) Gastroenteropancreatic Neuroendocrine Tumors. Front Endocrinol (Lausanne) 2022; 13:871830. [PMID: 35937823 PMCID: PMC9350735 DOI: 10.3389/fendo.2022.871830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 05/24/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Regional lymph node metastasis (LNM) is crucial for planning additional lymphadenectomy, and is directly correlated with poor prognosis in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the patterns of LNM for small (≤20 mm) GEP-NETs remain unclear. This population-based study aimed at evaluating LNM patterns and identifying optimal surgical strategies from the standpoint of lymph node dissemination. METHODS This retrospective cohort study retrieved data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database for 17,308 patients diagnosed as having localized well-differentiated GEP-NETs ≤ 20 mm between January 1, 2004, and December 31, 2017. The patterns of LNM were characterized in 6,622 patients who underwent extended resection for adequate lymph node harvest. RESULTS Of 6,622 patients with localized small GEP-NETs in the current study, 2,380 (36%) presented with LNM after regional lymphadenectomy. Nodal involvement was observed in approximately 7.4%, 49.1%, 13.6%, 53.7%, 13.8%, 7.8%, and 15.4% of gastric (g-), small intestinal (si-), appendiceal (a-), colonic (c-), rectal (r-), non-functional pancreatic (nfp-), and functional pancreatic (fp-) NETs ≤ 20 mm. Patients with younger age, larger tumor size, and muscularis invasion were more likely to present with LNM. Additional lymphadenectomy conferred a significant survival advantage in NETs (≤10 mm: HR, 0.47; 95% CI, 0.33-0.66; p < 0.001; 11-20 mm: HR, 0.54; 95% CI, 0.34-0.85; p = 0.008) and fp-NETs ≤ 20 mm (HR, 0.08; 95% CI, 0.02-0.36; p = 0.001), as well as g-NETs (HR, 0.39; 95% CI, 0.16-0.96; p = 0.041) and c-NETs of 11-20 mm (HR, 0.07; 95% CI, 0.01-0.48; p = 0.007). Survival benefits of additional lymphadenectomy were not found in a-NETs, r-NETs, and nfp-NETs with a small size. CONCLUSIONS Given the increased risk for nodal metastasis, primary tumor resection with regional lymphadenectomy is a potential optimal surgical strategy for si-NETs and fp-NETs ≤ 20 mm, as well as g-NETs and c-NETs of 11-20 mm. Local resection is an appropriate and reliable surgical approach for a-NETs, r-NETs, and nfp-NETs ≤ 20 mm.
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Affiliation(s)
| | | | | | | | | | - Haixing Ju
- *Correspondence: Yuping Zhu, ; Haixing Ju,
| | - Yuping Zhu
- *Correspondence: Yuping Zhu, ; Haixing Ju,
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20
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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.
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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
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21
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Jeong JH, Lee SY, Han HS, Kim JH, Sung IK, Park HS. Five Autoimmune Gastritis Patients with Positive Findings of Serum Anti-parietal Cell Antibodies. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0016] [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
Autoimmune gastritis is a corpus-dominant type of gastritis with positive serum anti-parietal cell antibodies (APCA) and/or anti-intrinsic factor antibodies. Serum APCA and pepsinogen (PG) assays were performed in subjects with corpus-dominant gastritis detected by endoscopy. Serum APCA was positive in five patients. All these patients were postmenopausal women (four Koreans and one Caucasian from the Russian Federation) with a mean age of 59.0±3.2 years. They displayed low PG I levels ranging from 8.1 to 18.8 ng/mL (mean, 11.4±4.8 ng/mL) and low PG I/II ratios ranging from 0.7 to 2.4 (mean, 1.2±0.7). Three of the patients were being treated for autoimmune thyroiditis. Multiple gastric neuroendocrine tumors were observed in two Helicobacter pylori (H. pylori)-naive patients with high serum gastrin levels exceeding 700 pg/mL and serum chromogranin A levels exceeding 1,000 ng/mL. In the remaining three patients, intestinal metaplasia was observed in the biopsied specimens from the antrum, suggesting a history of H. pylori infection. Our findings indicate the value of positive serum APCA findings, low serum PG I levels, and low serum PG I/II ratios in confirming autoimmune gastritis in patients showing corpus-dominant atrophy, regardless of their H. pylori infection status.
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22
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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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23
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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.
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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
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24
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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.
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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
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25
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Hu J, Liu W, Chen Z, Lin D, Su M, Lan P. A Novel Snare Traction-Assisted Method During Endoscopic Resection for Upper Gastrointestinal Submucosal Tumors. J Laparoendosc Adv Surg Tech A 2020; 31:416-422. [PMID: 32924769 DOI: 10.1089/lap.2020.0462] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: Traction-assisted endoscopic resection is an approach to provide better procedural outcomes than conventional endoscopic procedure in treating gastric or esophageal epithelial lesions. Submucosal tumors (SMTs) are challenging to resect endoscopically due to the difficulty in exposure and high incidence of full-thickness resection. In this study, we investigated the efficacy of snare traction-assisted method, served as an "extra hand," for upper gastrointestinal SMTs. Methods: From June 2019 to May 2020, we used the snare traction-assisted method to treat 11 patients with 12 upper gastrointestinal SMTs in the Sixth Affiliated Hospital, Sun Yat-sen University. The duration of the procedures and the outcomes were recorded. Results: A total of 11 patients with 12 lesions were treated by snare traction-assisted endoscopic resection. The mean procedure time was 26.8 ± 8.3 minutes. En bloc resection was achieved in all the 12 lesions. The mean length of the specimens was 11.5 ± 4.0 mm. Full-thickness resection was performed in four lesions. The patients were discharged in 5.0 days after procedures without delayed bleeding or other complication reported. Conclusion: Snare traction-assisted method is an effective tool for endoscopic resection of upper gastrointestinal SMTs. Further prospective studies comparing the snare traction-assisted method with the conventional procedure are necessary.
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Affiliation(s)
- Jiancong Hu
- Department of Endoscopic Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wei Liu
- Department of Endoscopic Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zexian Chen
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Dezheng Lin
- Department of Endoscopic Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Mingli Su
- Department of Endoscopic Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ping Lan
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
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26
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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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27
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Rossi RE, Invernizzi P, Mazzaferro V, Massironi S. Response and relapse rates after treatment with long-acting somatostatin analogs in multifocal or recurrent type-1 gastric carcinoids: A systematic review and meta-analysis. United European Gastroenterol J 2020; 8:140-147. [PMID: 32213066 PMCID: PMC7079271 DOI: 10.1177/2050640619890465] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 10/29/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Type-1 gastric neuroendocrine tumors represent a recurring disease and long-acting somatostatin analogs can inhibit both gastrin release and endocrine cell proliferation. The efficacy and timing of this treatment are still unclear. We performed a systematic review of the literature to clarify the role of somatostatin analog treatment in type-1 gastric neuroendocrine tumors. METHODS A computerized literature search was performed using relevant keywords to identify all the pertinent articles published in the last 15 years. RESULTS Eight studies were included in this systematic review on somatostatin analogs in type-1 gastric neuroendocrine tumors. A complete response rate ranged from 25-100%. When only the six prospective studies were considered, no significant heterogeneity was observed, and the pooled cumulative complete response rate was 84.5% (confidence interval 73.8-92.8). Three studies evaluated the type-1 gastric neuroendocrine tumor recurrence, with a cumulative relapse rate of 30.2% (confidence interval 13.1-50.6) after 34 months. CONCLUSION Somatostatin analogs, namely lanreotide and octreotide, have an excellent response rate, with a good safety profile in selected type-1 gastric neuroendocrine tumors, which cannot be safely managed by endoscopic follow-up or resection due to multiple or frequently recurring disease. After therapy discontinuation, the cumulative relapse rate observed after a median 34-month follow-up was relatively high (30.2%).
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Affiliation(s)
- Roberta Elisa Rossi
- Gastrointestinal and Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione, RCCS Istituto Nazionale Tumori (INT, National Cancer Institute) and Università degli Studi di Milano, Milan, Italy
| | - Pietro Invernizzi
- Department of Gastroenterology and Center for Liver Autoimmune Diseases, San Gerardo Hospital, Monza, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal and Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione, RCCS Istituto Nazionale Tumori (INT, National Cancer Institute) and Università degli Studi di Milano, Milan, Italy
| | - Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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28
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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.
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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
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29
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Daskalakis K, Tsoli M, Karapanagioti A, Chrysochoou M, Thomas D, Sougioultzis S, Karoumpalis I, Kaltsas GA, Alexandraki KI. Recurrence and metastatic potential in Type 1 gastric neuroendocrine neoplasms. Clin Endocrinol (Oxf) 2019; 91:534-543. [PMID: 31254407 DOI: 10.1111/cen.14055] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/16/2019] [Accepted: 06/27/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of our study was to assess clinico-pathological and biochemical parameters of Type 1 Gastric Neuroendocrine Neoplasms (GNEN1) with respect to tumours propensity for recurrence and metastasis. METHODS Hospital charts of GNEN1 patients were reviewed at a single tertiary referral centre. RESULTS We included 114 consecutive patients (74 women; age at baseline 54.5 ± 12.7 years [mean ± SD]) with GNEN1. All tumours (n = 114) were well differentiated; Grade 1 (G1) accounted for 56 patients (49%), whereas 46 (40%) were Grade 2 (G2) and 12 (11%) of unknown Grade. Overall follow-up encompassed 45.3 ± 46 (mean ± SD) months in 84 patients who were subjected to annual surveillance; 44 (52%) developed recurrence in the stomach during follow-up with 22 experiencing multiple recurrences; three (2.6%) presented with metastases in locoregional lymph nodes (n = 3) and/or the liver (n = 2); No metastasis or death was reported during follow-up. Median recurrence-free survival (RFS) was 31 months (95% CI: 7.6-54.4). Among clinico-pathological and biochemical parameters investigated, endoscopic intervention compared with surgery (P-value = .009) and higher serum-gastrin levels (s-gastrin) at baseline and first-year follow-up were associated with recurrence (P-value = .022 and .003 respectively) and also shorter RFS (log-rank P = .009 for type of intervention and .014 for s-gastrin, respectively). Receiver Operator Curve analysis of s-gastrin levels at first-year follow-up for recurrence demonstrated an area under the curve of 0.702. CONCLUSION Despite the relatively high prevalence of G2 tumours, endoscopically and/or surgically treated GNEN1 remains an indolent disease with a low metastatic propensity and no disease-specific mortality reported in our series. Many patients though will experience local recurrence, warranting long-term endoscopic surveillance with s-gastrin biomarker being a complementary tool in recurrence prediction.
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Affiliation(s)
- Kosmas Daskalakis
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Marina Tsoli
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Angeliki Karapanagioti
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Chrysochoou
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Thomas
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Stavros Sougioultzis
- Gastroenterology Division, Department of Pathophysiology, Laikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Karoumpalis
- Department of Gastroenterology, "G. Gennimatas" General Hospital, Athens, Greece
| | - Gregory A Kaltsas
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Krystallenia I Alexandraki
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
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30
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Tsolakis AV, Ragkousi A, Vujasinovic M, Kaltsas G, Daskalakis K. Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis. World J Gastroenterol 2019; 25:5376-5387. [PMID: 31558880 PMCID: PMC6761239 DOI: 10.3748/wjg.v25.i35.5376] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 06/12/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3% (25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8; heterogeneity: P = 0.126; I 2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2; 95%CI: 1.8-161.1; heterogeneity: P = 0.165; I 2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2; 95%CI: 0.3-11.6; heterogeneity: P = 0.304; I 2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3; 95%CI: 0.1-1.1; heterogeneity: P = 0.173; I 2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5-year disease-specific survival rates reported; hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.
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Affiliation(s)
- Apostolos V Tsolakis
- Department of Oncology and Pathology, Karolinska Institute, Stockholm 17177, Sweden
- Cancer Centre Karolinska, CCK, Karolinska University Hospital, Stockholm 17176, Sweden
| | - Athanasia Ragkousi
- 1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Miroslav Vujasinovic
- Department of Digestive Diseases, Karolinska University Hospital, Stockholm 14186, Sweden
| | - Gregory Kaltsas
- 1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Kosmas Daskalakis
- 1st Department of Propaupedic Internal Medicine, Endocrine Oncology Unit, Laiko Hospital, National and Kapodistrian University of Athens, Athens 11527, Greece
- Department of Surgical Sciences, Uppsala University, Uppsala 75185, Sweden
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31
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Crown A, Kennecke H, Kozarek R, Lopez-Aguiar AG, Dillhoff M, Beal EW, Poultsides GA, Makris E, Idrees K, Smith PM, Nathan H, Beems M, Abbott D, Fisher AV, Fields RC, Davidson J, Maithel SK, Rocha FG. Gastric carcinoids: Does type of surgery or tumor affect survival? Am J Surg 2019; 217:937-942. [PMID: 30686481 DOI: 10.1016/j.amjsurg.2018.12.057] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 12/10/2018] [Accepted: 12/27/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Gastric carcinoids are rare neuroendocrine tumors of the gastrointestinal tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients. METHODS All patients who underwent resection of gastric carcinoids at 8 institutions from 2000 to 2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection, LR or formal gastrectomy, FG). Clinicopathological parameters, recurrence-free (RFS) and overall survival (OS) were compared between groups. RESULTS Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p < 0.04 and p < 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p < 0.017). This trend persisted when type II and type IV groups were excluded (p < 0.045). CONCLUSION Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.
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Affiliation(s)
- Angelena Crown
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA
| | - Hagen Kennecke
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA
| | - Richard Kozarek
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Mary Dillhoff
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Eliza W Beal
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - George A Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Eleftherios Makris
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Paula Marincola Smith
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Hari Nathan
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Megan Beems
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Daniel Abbott
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Alexander V Fisher
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
| | - Jesse Davidson
- Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Flavio G Rocha
- Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, USA.
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Chen X, Li B, Wang S, Yang B, Zhu L, Ma S, Wu J, He Q, Zhao J, Zheng Z, Li S, Wang T, Liang L. Efficacy and safety of endoscopic submucosal dissection for gastrointestinal neuroendocrine tumors: a 10-year data analysis of Northern China. Scand J Gastroenterol 2019; 54:384-389. [PMID: 31037980 DOI: 10.1080/00365521.2019.1588367] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Objective: Endoscopy is the main method to treat gastrointestinal neuroendocrine tumors (GI-NETs), but the specific indications are still controversial. We aim to investigate the clinical outcomes of GI-NETs patients who experienced endoscopic submucosal dissection (ESD). Methods: We retrospectively reviewed the clinical features and prognosis of 65 GI-NETs patients who underwent ESD between 2008 and 2018. Results: A total of 65 patients diagnosed with GI-NETs pathologically, bearing 75 lesions, were found by endoscopy incidentally for other symptoms. The locations of these lesions were stomach (n = 24), duodenal bulb (n = 4) and rectum (n = 47). The diameter of 75 tumors were as follows: size ≤ 1 cm (78.7%), 1 cm < size ≤ 2 cm (17.3%), 2 cm < size ≤ 3.5 cm (4.0%). Endoscopic ultrasonography (EUS) suggested that 72 lesions were confined to submucosa and 3 lesions invaded into muscularis propria. The rates of en bloc resection and complete resection were all 100% and the rates of intraoperative bleeding and perforation were 2.7% and 1.3%, respectively. None of the 65 patients had lymph nodes and distant metastasis during the period of study. Conclusion: For GI-NETs without lymph nodes and distant metastases, the lesion confined to submucosa with the diameter ≤1 cm is absolute indication of ESD. For rectal neuroendocrine tumors limited in submucosa with the diameter between 1 and 2 cm, and Type 1 gastric neuroendocrine tumors predicted to be T2, ESD should be prioritized to preserve gastrointestinal volume and function at initial treatment.
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Affiliation(s)
- Xin Chen
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Bianxia Li
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Saiyu Wang
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | | | | | - Shuang Ma
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Jingyi Wu
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Qijin He
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Jingwen Zhao
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Zhongqing Zheng
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Shu Li
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Tao Wang
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
| | - Li Liang
- a Department of Gastroenterology and Hepatology , General Hospital, Tianjin Medical University , Tianjin , China
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Kubo K, Kimura N, Mabe K, Nishimura Y, Kato M. Synchronous Triple Gastric Cancer Incorporating Mixed Adenocarcinoma and Neuroendocrine Tumor Completely Resected with Endoscopic Submucosal Dissection. Intern Med 2018; 57:2951-2955. [PMID: 29780136 PMCID: PMC6232031 DOI: 10.2169/internalmedicine.0842-18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
The endoscopic and pathological features of early gastric mixed adenoneuroendocrine carcinoma (MANEC), as well as its carcinogenesis, remain largely unclear. Screening esophagogastroduodenoscopy was performed on an 80-year-old man, revealing 3 superficial elevated lesions. Endoscopic submucosal dissection (ESD) was performed, and the patient was diagnosed with intramucosal gastric cancer comprising mixed adenocarcinoma and neuroendocrine tumor, well-differentiated adenocarcinoma and well-differentiated adenocarcinoma, with negative margins. To our knowledge, this is the first report describing the endoscopic and pathological findings of synchronous triple gastric cancer incorporating mixed adenocarcinoma and neuroendocrine tumor completely resected with ESD.
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Affiliation(s)
- Kimitoshi Kubo
- Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Japan
| | - Noriko Kimura
- Department of Pathology, National Hospital Organization Hakodate Hospital, Japan
| | - Katsuhiro Mabe
- Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Japan
| | - Yusuke Nishimura
- Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Japan
| | - Mototsugu Kato
- Department of Gastroenterology, National Hospital Organization Hakodate Hospital, Japan
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Chung CS, Tsai CL, Chu YY, Chen KC, Lin JC, Chen BC, Sun WC, Yen HH, Chen CY, Wu IC, Kuo CH, Shih HY, Bair MJ, Wang JP, Hu WH, Yang CS, Han ML, Cheng TY, Tseng CM, Tsai MC, Hu ML, Wang HP. Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A Digestive Endoscopy Society of Tawian (DEST). Medicine (Baltimore) 2018; 97:e12101. [PMID: 30235663 PMCID: PMC6160255 DOI: 10.1097/md.0000000000012101] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Gastric neuroendocrine tumors (GNETs) are a heterogeneous group of neoplasm with varying biological characteristics. This study aimed to investigate the clinical features and outcomes of GNET patients after endoscopic diagnosis and treatment in a multicenter registry. Patients with GNETs confirmed histologically were recruited from 17 hospitals between January 2010 and April 2016 in Taiwan. Clinical, laboratory, radiological, endoscopic, pathological data, treatment strategies, follow-up periods, and survivals were collected retrospectively. Totally 187 (107 female, 80 male) patients were recruited. Mean ( ± standard deviation [SD]) age and size of tumors were 63.2-year-old ( ± 14.6) and 2.3-cm ( ± 3.0). World Health Organization (WHO) grading were 93 (49.7%) G1, 26 (13.9%) G2, 40 (21.4%) G3, and 28 (15.0%) unknown. G3 patients were older (mean ± SD, 71.6 ± 12.4 vs. 60.9 ± 14.3/56.7 ± 15.4 years), larger (6.1 ± 4.0 vs.1.2 ± 1.3/2.4 ± 2.5 cm), more distally located (35.0% vs. 7.6%/15.4%), lower proportion of superficial lesions (17.5% vs. 61.9%/53.8%) and higher rates of lymphovascular invasion (32.5% vs. 3.2%/7.7%) than G1/G2. There was no nodal or distant organ metastases despite different grading of lesions≦10 mm and those <20 mm limited to mucosa and submucosa layers. GNETs larger than 20 mm with G1, G2, and G3 had lymph node (LN) metastatic rates of 21.4%, 30.0%, and 59.3%, respectively. Survivals were different between grading for those >20 mm (log-rank test P = .02). Male gender (P = .01), deeper invasion (P = .0001), nodal (P < .0001), and distant organ metastases (P = .0001) were associated with worse outcome. In conclusion, treatment strategies for GNET should be decided by grading, size, invasiveness, and LN metastasis risk. Curative endoscopic resection is feasible for G1/2 lesions less than 20 mm and limited to mucosa/submucosa layers without lymphovascular invasion.
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Affiliation(s)
- Chen-Shuan Chung
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Banciao District
- College of Medicine, Fu Jen Catholic University, New Taipei City
| | - Cho-Lun Tsai
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei
- Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi
| | - Yin-Yi Chu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan
| | - Kuan-Chih Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Banciao District
| | - Jung-Chun Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei
| | - Bao-Chung Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei
| | - Wei-Chih Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veteran General Hospital, Kaohsiung
| | - Hsu-Heng Yen
- Endoscopy Center, Changhua Christian Hospital, Changhua City
| | - Chiung-Yu Chen
- Division of Gastroenterology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan
| | - I-Chen Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - Hisang-Yao Shih
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital
| | - Jack P. Wang
- Division of Gastroenterology, Department of Internal Medicine, Taipei City Hospital, Renai Branch, Taipei
| | - Wen-Hao Hu
- Department of Internal Medicine, National Taiwan University Hospital, Hsinchu branch, Hsinchu
| | | | - Ming-Lun Han
- Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan
| | - Tsu-Yao Cheng
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei
- Department of Laboratoty Medicine, National Taiwan University Hospital, Taipei
| | - Chao-Ming Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung
| | - Ming-Chang Tsai
- Division of Gastroenterology, Chung Shan Medical University Hospital, Taichung
| | - Ming-Luen Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei
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Shinozaki S, Osawa H, Kobayashi Y, Sakamoto H, Hayashi Y, Miura Y, Kawarai Lefor A, Yamamoto H. Long-term outcomes of patients with symptomatic gastroesophageal reflux disease treated with vonoprazan. Scand J Gastroenterol 2018; 53:897-904. [PMID: 30056768 DOI: 10.1080/00365521.2018.1486883] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE The novel potassium-competitive acid blocker, vonoprazan, provides rapid and effective acid suppression. The aim of this study is to evaluate the long-term outcomes of patients with symptomatic gastroesophageal reflux disease (GERD) treated with vonoprazan. METHODS This retrospective cohort study included 55 patients with symptomatic GERD treated with vonoprazan who have been followed for more than one year. The effectiveness of vonoprazan on gastrointestinal symptoms was evaluated using the Izumo scale, a self-reported questionnaire reflecting quality of life related to various abdominal symptoms. RESULTS These 55 patients with symptomatic GERD had non-erosive reflux disease (n = 30) or erosive esophagitis (n = 25). Vonoprazan (10 mg) for one month improved GERD symptoms in 89% (responders) and the improvement was maintained at one year in 82% without additional treatment. One-year maintenance therapy resulted in sustained resolution of GERD symptoms in 47%. Of the 49 responders, nine patients had relapse of GERD symptoms and dose escalation of vonoprazan improved the symptoms in six patients. Postprandial distress and the presence of erosive esophagitis before starting vonoprazan were identified as significant negative and positive predictors of sustained resolution of GERD symptoms for one year, respectively. Epigastric pain, postprandial distress, constipation and diarrhea were significantly improved at one-month and maintained at one year. After one-year of treatment, the endoscopic healing rate of erosive esophagitis was 95%. CONCLUSION One-year treatment with vonoprazan significantly improves GERD symptoms and endoscopic healing of erosive esophagitis is satisfactory. The long-term use of vonoprazan is effective and useful to control GERD.
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Affiliation(s)
- Satoshi Shinozaki
- a Shinozaki Medical Clinic , Utsunomiya , Japan.,b Division of Gastroenterology Department of Medicine , Jichi Medical University , Shimotsuke , Japan
| | - Hiroyuki Osawa
- b Division of Gastroenterology Department of Medicine , Jichi Medical University , Shimotsuke , Japan
| | - Yasutoshi Kobayashi
- b Division of Gastroenterology Department of Medicine , Jichi Medical University , Shimotsuke , Japan
| | - Hirotsugu Sakamoto
- b Division of Gastroenterology Department of Medicine , Jichi Medical University , Shimotsuke , Japan
| | - Yoshikazu Hayashi
- b Division of Gastroenterology Department of Medicine , Jichi Medical University , Shimotsuke , Japan
| | - Yoshimasa Miura
- b Division of Gastroenterology Department of Medicine , Jichi Medical University , Shimotsuke , Japan
| | | | - Hironori Yamamoto
- b Division of Gastroenterology Department of Medicine , Jichi Medical University , Shimotsuke , Japan
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Kinoshita Y, Ishimura N, Ishihara S. Advantages and Disadvantages of Long-term Proton Pump Inhibitor Use. J Neurogastroenterol Motil 2018; 24:182-196. [PMID: 29605975 PMCID: PMC5885718 DOI: 10.5056/jnm18001] [Citation(s) in RCA: 140] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Revised: 01/28/2018] [Accepted: 02/09/2018] [Indexed: 12/13/2022] Open
Abstract
Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, even though their beneficial effects for those conditions have not been fully confirmed. PPIs tend to be given for conditions in which the necessity of the drug has not been clarified, thus otherwise rare adverse effects are presented as clinically relevant. Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit and to continue to investigate their adverse effects with high quality prospective studies.
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Affiliation(s)
- Yoshikazu Kinoshita
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane,
Japan
| | - Norihisa Ishimura
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane,
Japan
| | - Shunji Ishihara
- Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Shimane,
Japan
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Igarashi R, Irisawa A, Shibukawa G, Soeta N, Sato A, Yamabe A, Fujisawa M, Arakawa N, Yoshida Y, Ikeda T, Abe Y, Maki T, Yamamoto S, Oshibe I, Saito T, Hojo H. Case Report of a Small Gastric Neuroendocrine Tumor in a Deep Layer of Submucosa With Diagnosis by Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Treatment With Laparoscopic and Endoscopic Cooperative Surgery. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2018; 11:1179547617749226. [PMID: 29371789 PMCID: PMC5768268 DOI: 10.1177/1179547617749226] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 09/29/2017] [Indexed: 12/24/2022]
Abstract
Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by enterochromaffin-like cells of the stomach. Optimal management of GNETs has not yet been definitively determined. Endoscopic resection is approximately recommended for small GNETs associated with hypergastrinemia. However, endoscopic resection might present risk of perforation or positive vertical margin because neuroendocrine tumors occur in the deep mucosa, with some invading the submucosa. In this case, a patient with type A chronic atrophic gastritis had a small subepithelial lesion in a deep submucosal layer, and we diagnosed it as GNET using endoscopic ultrasound-guided fine-needle aspiration biopsy using a forward-viewing and curved linear-array echoendoscope. Moreover, our results show that laparoscopic and endoscopic cooperative surgery with regional lymph node dissection is a safe and feasible procedure for GNETs, especially those that cross to the muscularis propria. We suggest this approach as one therapeutic option for GNETs because it safely minimizes resection and is less invasive.
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Affiliation(s)
- Ryo Igarashi
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Atsushi Irisawa
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Goro Shibukawa
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Nobutoshi Soeta
- Department of Surgery, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Ai Sato
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Akane Yamabe
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Mariko Fujisawa
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Noriyuki Arakawa
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Yoshitsugu Yoshida
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Tsunehiko Ikeda
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Yoko Abe
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Takumi Maki
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Shogo Yamamoto
- Department of Gastroenterology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Ikuro Oshibe
- Department of Surgery, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Takuro Saito
- Department of Surgery, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
| | - Hiroshi Hojo
- Department of Pathology, Aizu Medical Center, Fukushima Medical University, Fukushima, Japan
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Manfredi S, Walter T, Baudin E, Coriat R, Ruszniewski P, Lecomte T, Laurenty AP, Goichot B, Rohmer V, Roquin G, Cojocarasu OZ, Lombard-Bohas C, Lepage C, Morcet J, Cadiot G. Management of gastric neuro-endocrine tumours in a large French national cohort (GTE). Endocrine 2017; 57:504-511. [PMID: 28664309 DOI: 10.1007/s12020-017-1355-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 06/13/2017] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Gastric neuro-endocrine tumours are rare. European guidelines for the management of neuro-endocrine tumours have been published in 2012. The aim of our survey was to study the management of gastric neuro-endocrine tumours registered in the national cohort. A prospective national cohort registers the Neuro-endocrine tumours in France since January 2003 (GTE network). We reviewed all the individual medical reports of gastric neuro-endocrine tumours in order to collect data on treatment. RESULTS One hundred and ninety seven gastric neuro-endocrine tumours diagnosed between 1964 and 2013 in 20 centres were registered. For 181 cases data were considered complete for our survey. Eighty four tumours were type 1 (46.4%); five types 2 (2.8%); 52 types 3 (28.7%) and 40 types 4 (22.1%). Types 1 and 2 were first endoscopically managed in 93 and 60% of cases, respectively, whereas surgery was first done in 45 and 42%, respectively, of types 3 and 4. Systemic treatment, chemotherapy and/or somatostatin analogue, was first administered exclusively for types 3 and 4. Near 3% of types 1 and 40% of types 2 received at a time somatostatin analogue treatment. Five-year survival rates were 98.3, 100, 63.2 and 31.8% for types 1, 2, 3 and 4, respectively. CONCLUSION The great majority of gastric neuro-endocrine tumours registered in this national cohort are treated in accordance with the current guidelines. The survival rates we reported must be interpreted with caution, because this cohort registered preferentially selected patients eligible for treatment. The registration of all the gastric neuro-endocrine tumours, in particular type 1 considered as benign and type 4 not eligible for specific anti-cancer treatment must be encouraged.
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Affiliation(s)
- Sylvain Manfredi
- CHU Dijon, hepato-gastroenterology unit, University of Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21000, Dijon, France.
| | - Thomas Walter
- Département d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, cedex 03, France
| | - Eric Baudin
- Gustave Roussy, Département d'Oncologie Endocrinienne, 94805, Villejuif cedex, France
| | - Romain Coriat
- Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, Paris Descartes University, Paris, France
| | | | - Thierry Lecomte
- CHRU de Tours, service d'Hépato-Gastroenterologie, CNRS, UMR 7292, GICC & Université Francois-Rabelais, Tours, France
| | | | - Bernard Goichot
- Department of Internal Medicine, Endocrinology and Nutrition, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
| | - Vincent Rohmer
- Service d'endocrinologie et maladies métaboliques, CHU d'Angers, 4 rue Larrey, 49100, Angers, France
| | | | | | - Catherine Lombard-Bohas
- Département d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, cedex 03, France
| | - Côme Lepage
- CHU Dijon, hepato-gastroenterology unit, University of Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21000, Dijon, France
| | | | - Guillaume Cadiot
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France
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Sato Y, Hashimoto S, Mizuno KI, Takeuchi M, Terai S. Management of gastric and duodenal neuroendocrine tumors. World J Gastroenterol 2016; 22:6817-6828. [PMID: 27570419 PMCID: PMC4974581 DOI: 10.3748/wjg.v22.i30.6817] [Citation(s) in RCA: 101] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 06/16/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type I, II, and III. Type I G-NETs, which are the most common subtype (70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type II G-NETs (5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Both type I and II G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type III G-NETs (10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type III G-NETs, while endoscopic resection and follow-up, which are acceptable for the treatment of most type I and II G-NETs, are only acceptable for small and well differentiated type III G-NETs. D-NETs include gastrinomas (50%-60%), somatostatin-producing tumors (15%), nonfunctional serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinomas (< 3%), and gangliocytic paragangliomas (< 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs (G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.
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Postlewait LM, Baptiste GG, Ethun CG, Le N, Cardona K, Russell MC, Willingham FF, Kooby DA, Staley CA, Maithel SK. A 15-year experience with gastric neuroendocrine tumors: Does type make a difference? J Surg Oncol 2016; 114:576-580. [PMID: 27393718 DOI: 10.1002/jso.24369] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 06/21/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastric neuroendocrine tumors (GNETs) are rare and classified into three types by disease etiology and typical behavior. METHODS The aim was to describe outcomes after GNET resection at a single institution from 2000 to 2014, stratified by tumor type. Given the small patient number, P-values were not assigned. RESULTS Of 22 patients, 12 patients (55%) had Type 1, none (0%) had Type 2, and 10 (45%) had Type 3 tumors. Compared to Type 3, Type 1 patients were younger (mean age: 52 vs. 59 years) with similar rates of endoscopic resection (25% vs. 20%). Type 1 GNETs often had multiple tumors (60% vs. 10%) and were not poorly differentiated (0% vs. 11%). Only 33% of Type 1 had nodal metastases compared to 71% of Type 3. Type 1 GNETs presented with metastatic disease less often (17% vs. 40%). Three year recurrence-free survival was 33% for Type 1 compared to 86% for Type 3. Disease-specific survival at 3-years was 100% and 75% for Types 1 and 3, respectively. CONCLUSION Type 1 GNETs are often indolent and multifocal without nodal involvement, but have high recurrence risk. Type 3 is more aggressive with increased nodal involvement; nodal evaluation should be routinely performed. Determination of GNET type is paramount to treating patients with this rare disease. J. Surg. Oncol. 2016;114:576-580. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Lauren M Postlewait
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Gillian G Baptiste
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Cecilia G Ethun
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Nina Le
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Kenneth Cardona
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Maria C Russell
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Field F Willingham
- Division of Gastroenterology, Department of Internal Medicine, Emory University, Atlanta, Georgia
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Charles A Staley
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia.
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Fendrich V, Bartsch DK. Chirurgische Therapie gastroduodenaler neuroendokriner Neoplasien. Chirurg 2016; 87:280-7. [PMID: 26779647 DOI: 10.1007/s00104-015-0138-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Campana D, Ravizza D, Ferolla P, Faggiano A, Grimaldi F, Albertelli M, Berretti D, Castellani D, Cacciari G, Fazio N, Colao A, Ferone D, Tomassetti P. Clinical management of patients with gastric neuroendocrine neoplasms associated with chronic atrophic gastritis: a retrospective, multicentre study. Endocrine 2016; 51:131-9. [PMID: 25814125 DOI: 10.1007/s12020-015-0584-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Accepted: 03/19/2015] [Indexed: 12/19/2022]
Abstract
To provide data regarding clinical presentation, pathological features, management, and response to different treatments of patients with type I gastric neuroendocrine tumors in stages 0-2A. The study design consist of an Italian multicentre, retrospective analysis of patients with type I gastric neuroendocrine tumors managed with different therapeutic approaches: surgery, endoscopic surveillance, endoscopic resection, or somatostatin analog therapy. Among the 97 patients included, 3 underwent surgery, 45 (46.4%) radical endoscopic resection of the neoplastic lesions, 13 (13.4%) follow-up with upper endoscopy, and 36 (37.1%) somatostatin analog therapy. At the end of the follow-up, all patients were alive and there was no evidence of metastatic disease. Somatostatin analog therapy resulted in a complete response in 76.0% of the patients and stable disease in 24.0%. A prolonged period of therapy, the use of a full dose of somatostatin analogs and higher gastrin levels at diagnosis were related to a complete response to the therapy. The recurrence rate was 26.3% in patients treated with somatostatin analog therapy and 26.2% in patients treated with endoscopic resection, without a statistically significant difference in terms of disease-free survival. Regarding recurrence of the disease, no statistical difference was found according to type of therapy, number of neoplastic lesions, and 2010 WHO classification. The only risk factor for tumor recurrence was a short period of medical treatment. In conclusion, our study suggested that endoscopic surveillance, endoscopic resection and somatostatin analog therapy represent valid options in the management of patients with type I gastric neuroendocrine tumors in stages 0-2A.
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Affiliation(s)
- Davide Campana
- Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy.
| | - Davide Ravizza
- Division of Endoscopy and Unit of Gastrointestinal and Neuroendocrine Tumours, European Institute of Oncology, Milan, Italy
| | - Piero Ferolla
- Department of Medical Oncology, Multidisciplinary NET Center, Umbria Regional Cancer Network, Umbria, Italy
| | - Antongiulio Faggiano
- Division of Endocrinology, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Franco Grimaldi
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia, Udine, Italy
| | - Manuela Albertelli
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI) and Center of Excellence for Biomedical Research (CEBR), University of Genova, Genoa, Italy
- IRCCS-AOU San Martino-IST, Genoa, Italy
| | - Debora Berretti
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia, Udine, Italy
| | - Danilo Castellani
- Department of Gastroenterology, Multidisciplinary NET Center, Umbria Regional Cancer Network, Umbria, Italy
| | - Giulia Cacciari
- Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy
| | - Nicola Fazio
- Division of Endoscopy and Unit of Gastrointestinal and Neuroendocrine Tumours, European Institute of Oncology, Milan, Italy
| | - Annamaria Colao
- Division of Endocrinology, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Diego Ferone
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI) and Center of Excellence for Biomedical Research (CEBR), University of Genova, Genoa, Italy
- IRCCS-AOU San Martino-IST, Genoa, Italy
| | - Paola Tomassetti
- Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy
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Massironi S, Zilli A, Fanetti I, Ciafardini C, Conte D, Peracchi M. Intermittent treatment of recurrent type-1 gastric carcinoids with somatostatin analogues in patients with chronic autoimmune atrophic gastritis. Dig Liver Dis 2015; 47:978-983. [PMID: 26321479 DOI: 10.1016/j.dld.2015.07.155] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2015] [Revised: 07/27/2015] [Accepted: 07/30/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Optimal management and treatment of type-1 gastric carcinoids is under debate. AIMS This prospective study evaluates the outcome of patients with recurrent type-1 gastric carcinoids treated with somatostatin analogues. METHODS From 2000 to 2013, among a population of 107 chronic atrophic gastritis patients, 25 (20% males, median age 62 years) developed type-1 gastric carcinoids and underwent regular clinical and endoscopic follow-up (median 77 months, range 6-165) after the initial treatment. Those patients showing recurrent disease were treated with somatostatin analogues until carcinoid disappearance. RESULTS 12/25 patients (33% males, median age 65 years) showed recurrent gastric carcinoids and were treated with somatostatin analogues for a median duration of 12 months. Median gastrin and chromogranin A levels, which were 802 pg/mL and 33 U/L, respectively, decreased to 299 pg/mL (p=0.002) and 15.6 U/L (p=0.001) at the end of the treatment. Gastric carcinoids disappeared after a median length of treatment of 12 months. After a median time of 19.5 months from somatostatin analogues discontinuation, 4/12 patients (25% males, median age 56 years) showed a further recurrence. A new cycle of treatment was performed successfully. CONCLUSIONS This study confirms that type-1 gastric carcinoids are a recurring disease and somatostatin analogues, administered on 12-month cycles, represent an effective treatment.
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Affiliation(s)
- Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Alessandra Zilli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Ilaria Fanetti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Clorinda Ciafardini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Maddalena Peracchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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Massironi S, Zilli A, Conte D. Somatostatin analogs for gastric carcinoids: For many, but not all. World J Gastroenterol 2015; 21:6785-6793. [PMID: 26078554 PMCID: PMC4462718 DOI: 10.3748/wjg.v21.i22.6785] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Revised: 02/22/2015] [Accepted: 04/16/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric carcinoids (GCs) are classified as: type I, related to hypergastrinemia due to chronic atrophic gastritis (CAG), type II, associated with Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1, and type III, which is normogastrinemic. The management of type-I gastric carcinoids (GC1s) is still debated, because of their relatively benign course. According to the European Neuroendocrine Tumor Society guidelines endoscopic resection is indicated whenever possible; however, it is not often feasible because of the presence of a multifocal disease, large lesions, submucosal invasion or, rarely, lymph node involvement. Therefore, somatostatin analogs (SSAs) have been proposed as treatment for GC1s in view of their antisecretive, antiproliferative and antiangiogenic effects. However, in view of the high cost of this therapy, its possible side effects and the relatively benign course of the disease, SSAs should be reserved to specific subsets of "high risk patients", i.e., those patients with multifocal or recurrent GCs. Indeed, it is reasonable that, after the development of a gastric neuroendocrine neoplasm in patients with a chronic predisposing condition (such as CAG), other enterochromaffin-like cells can undergo neoplastic proliferation, being chronically stimulated by hypergastrinemia. Therefore, definite indications to SSAs treatment should be established in order to avoid the undertreatment or overtreatment of GCs.
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Abstract
Submucosal gastrointestinal tumors represent a unique, diverse and challenging group of lesions found in modern medical practice. While management has traditionally been surgical, the development of advanced endoscopic techniques is challenging this approach. This review aims to investigate the role of endotherapy in treatment pathways, with a focus on carcinoid and gastrointestinal stromal tumors. In particular, we will discuss which lesions can be safely treated endoscopically, the evidence base behind such approaches and the limitations of the current evidence. The review will consider how these techniques may change the management of submucosal tumors in the future.
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Sato Y. Endoscopic diagnosis and management of type I neuroendocrine tumors. World J Gastrointest Endosc 2015; 7:346-353. [PMID: 25901213 PMCID: PMC4400623 DOI: 10.4253/wjge.v7.i4.346] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 12/09/2014] [Accepted: 01/12/2015] [Indexed: 02/05/2023] Open
Abstract
Type I gastric neuroendocrine tumors (TI-GNETs) are related to chronic atrophic gastritis with hypergastrinemia and enterochromaffin-like cell hyperplasia. The incidence of TI-GNETs has significantly increased, with the great majority being TI-GNETs. TI-GNETs present as small (< 10 mm) and multiple lesions endoscopically and are generally limited to the mucosa or submucosa. Narrow band imaging and high resolution magnification endoscopy may be helpful for the endoscopic diagnosis of TI-GNETs. TI-GNETs are usually histologically classified by World Health Organization criteria as G1 tumors. Therefore, TI-GNETs tend to display nearly benign behavior with a low risk of progression or metastasis. Several treatment options are currently available for these tumors, including surgical resection, endoscopic resection, and endoscopic surveillance. However, debate persists about the best management technique for TI-GNETs.
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Lahner E, Galli G, Esposito G, Pilozzi E, Corleto VD, Annibale B. Updated features associated with type 1 gastric carcinoids patients: a single-center study. Scand J Gastroenterol 2014; 49:1447-1455. [PMID: 25309981 DOI: 10.3109/00365521.2014.968859] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE Data on clinical presentation and associated features of patients with type 1 gastric carcinoids (T1-GCs) are scanty. This study aimed to provide detailed data on a series of patients with T1-GCs. MATERIAL AND METHODS Clinical, laboratory, endoscopic, and histological data were assessed from 31 T1-GCs patients (cross-sectional design), consecutively diagnosed in a tertiary center according to a standardized diagnostic protocol. T1-GCs were diagnosed at baseline or follow-up gastroscopy for atrophic gastritis in 74.2% and 25.8% of patients, respectively. RESULTS Seventy-one percent of T1-GC patients were female. Age ranged from 23 to 78 (median 58 years). T1-GCs were more frequently diagnosed between 40-49 years (35.5%) and 60-69 years (32.3%) (p = 0.0383). Thyroid disease was present in 54.8% (in 29% autoimmune). All 31 patients had either cobalamin or iron deficiency with or without anemia. Manifest pernicious anemia was present in 67.7% of patients and cobalamin deficiency without anemia in 9.7% patients. Iron deficiency anemia was present in 29% and iron deficiency without anemia in 12.9% of patients. In 48.4% of patients, T1-GCs appeared as polyps, which were single in all cases and had a median size of 4 mm (range 2-15 mm). In patients with polypoid T1-GCs, thyroid disease of autoimmune and nonautoimmune origin (p = 0.0181) was more frequently associated. CONCLUSION This study shows that T1-GCs may be diagnosed at any age. Autoimmune features are frequently present as well as cobalamin and iron deficiency. The copresence of autoimmune diseases and micronutrient deficiencies should be accurately investigated, in particular in patients with polypoid T1-GCs.
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Affiliation(s)
- Edith Lahner
- Department of Digestive and Liver Disease, Sant'Andrea Hospital, Medical School, Sapienza University , Rome , Italy
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Sato Y. Clinical features and management of type I gastric carcinoids. Clin J Gastroenterol 2014; 7:381-6. [PMID: 26184015 DOI: 10.1007/s12328-014-0528-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Accepted: 09/02/2014] [Indexed: 12/14/2022]
Abstract
Type I gastric carcinoids (TIGCs) are related to chronic atrophic gastritis and are characterized by hypergastrinemia and hyperplasia of enterochromaffin-like cells. TIGCs are the most frequently diagnosed of all gastric carcinoids, accounting for about 70-80 %. Endoscopically, TIGCs are present as small (<10 mm), polypoid lesions or, more frequently, as smooth, rounded submucosal lesions. Histologically, TIGCs arise in the deep mucosa, with some invading the submucosa. Most TIGCs are well-differentiated tumors, with metastasis being rare. Therefore, patients with TIGCs generally have an excellent prognosis. Among the currently available treatment options are total gastrectomy, partial resection, antrectomy, endoscopic resection, and endoscopic surveillance, although no consensus has been reached on their optimal management. Further studies are needed to develop better management options for patients with TIGC.
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Affiliation(s)
- Yuichi Sato
- Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, 951-8121, Japan,
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