|
1
|
Jang JO, Jang WJ, Choi CW, Choi EJ, Kim SJ, Ryu DG, Park SB, Chung JH, Lee SH, Hwang SH. A single center retrospective analysis of feasibility of diagnostic endoscopic resection for grade 1 or 2 gastric neuroendocrine tumors. Sci Rep 2025; 15:16315. [PMID: 40348849 PMCID: PMC12065875 DOI: 10.1038/s41598-025-99791-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 04/23/2025] [Indexed: 05/14/2025] Open
Abstract
Currently, endoscopic resection is recommended for gastric neuroendocrine tumors (G-NETs) < 10 mm. However, a larger G-NETs can also be resected endoscopically. Here, we evaluated the feasibility of diagnostic endoscopic resection of G-NETs. We retrospectively analyzed 31 patients, diagnosed with grade 1 or 2 G-NETs at a single tertiary referral center, between January 2009 and December 2023. Outcomes analyzed included histopathology, complete resection, and metastasis rates. The mean follow-up period was 38.9 ± 38.4 months; mean size of G-NETs was 4.9 ± 3.4 mm, and the most size of G-NETs were < 10 mm (87.1%). The maximal NET diameter was 16 mm. Most NETs were grade 1 (type 1: 90.9%; type 3: 85.0%). None of the enrolled patients showed evidence of lymph node metastasis or local recurrence. Even in R1 resection (19.4%) showed no metastasis during follow-up without additional surgery. Recurrent or multiple G-NETs were observed only in patients with type 1 NETs (27.2%, 3/11). Modified endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) showed a 100% complete resection rate. After resection, grade 1 or 2 G-NETs had no lymph nodes or distant metastases during the follow-up period. This study suggests that G-NETs smaller than 16 mm can be considered for diagnostic endoscopic resection and this resection may be potentially definitive treatment.
Collapse
Affiliation(s)
- Jin Ook Jang
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Won Jun Jang
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Cheol Woong Choi
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea.
| | - Eun Jeung Choi
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Su Jin Kim
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Dae Gon Ryu
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Su Bum Park
- Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri Mulgeum-eup, Yangsan-si, Gyeongsangnam-do, 50612, Republic of Korea
| | - Jae Hun Chung
- Department of Surgery, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Si Hak Lee
- Department of Surgery, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sun Hwi Hwang
- Department of Surgery, Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| |
Collapse
|
|
2
|
Ma XZ, Zhou N, Luo X, Guo SQ, Mai P. Update understanding on diagnosis and histopathological examination of atrophic gastritis: A review. World J Gastrointest Oncol 2024; 16:4080-4091. [DOI: 10.4251/wjgo.v16.i10.4080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 08/14/2024] [Accepted: 08/21/2024] [Indexed: 09/26/2024] Open
Abstract
Chronic atrophic gastritis (CAG) is a complex syndrome in which long-term chronic inflammatory stimulation causes gland atrophy in the gastric mucosa, reducing the stomach's ability to secrete gastric juice and pepsin, and interfering with its normal physiological function. Multiple pathogenic factors contribute to CAG incidence, the most common being Helicobacter pylori infection and the immune reactions resulting from gastric autoimmunity. Furthermore, CAG has a broad spectrum of clinical manifestations, including gastroenterology and extra-intestinal symptoms and signs, such as hematology, neurology, and oncology. Therefore, the initial CAG evaluation should involve the examination of clinical and serological indicators, as well as diagnosis confirmation via gastroscopy and histopathology if necessary. Depending on the severity and scope of atrophy affecting the gastric mucosa, a histologic staging system (Operative Link for Gastritis Assessment or Operative Link on Gastritis intestinal metaplasia) could also be employed. Moreover, chronic gastritis has a higher risk of progressing to gastric cancer (GC). In this regard, early diagnosis, treatment, and regular testing could reduce the risk of GC in CAG patients. However, the optimal interval for endoscopic monitoring in CAG patients remains uncertain, and it should ideally be tailored based on individual risk evaluations and shared decision-making processes. Although there have been many reports on CAG, the precise etiology and histopathological features of the disease, as well as the diagnosis of CAG patients, are yet to be fully elucidated. Consequently, this review offers a detailed account of CAG, including its key clinical aspects, aiming to enhance the overall understanding of the disease.
Collapse
Affiliation(s)
- Xiu-Zhen Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
| | - Ni Zhou
- Department of Gastroenterology, Xi'an International Medical Center, Xi’an 710000, Shaanxi Province, China
| | - Xiu Luo
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Si-Qi Guo
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
- The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
| | - Ping Mai
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
| |
Collapse
|
|
3
|
Kunstman JW, Nagar A, Gibson J, Kunz PL. Modern Management of Gastric Neuroendocrine Neoplasms. Curr Treat Options Oncol 2024; 25:1137-1152. [PMID: 39083164 DOI: 10.1007/s11864-024-01207-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2024] [Indexed: 09/22/2024]
Abstract
OPINION STATEMENT Gastric neuroendocrine neoplasms (G-NENs) are a heterogeneous group of tumors that broadly fall into two groups. The first group, driven by oversecretion of gastrin, are generally multifocal, small, and behave indolently with a low (but non-zero) risk of progression and metastatic spread. They are conventionally categorized into type 1, with endogenous gastric-based overproduction of gastrin, and type 2 G-NEN, with overproduction of gastrin from an extra-gastric gastrin-secreting tumor. The second group, termed type 3 G-NEN, occur spontaneously and are potentially more aggressive, having a clinical course analogous to other neuroendocrine tumors of the gastrointestinal tract. Type 1 G-NEN can be managed with endoscopic surveillance and resection of visible lesions with great success, reserving surgery for the rare high-risk lesion, whereas surgical resection of the causative gastrin-secreting tumor in type 2 G-NEN is usually curative. Type 3 G-NEN is usually managed with formal surgical resection but there is growing evidence that limited surgery or even endoscopic resection in appropriately selected patients with low risk is both safe and effective. A novel subtype of G-NEN, associated with long-term proton pump inhibitor usage, is increasing in incidence. The pathophysiology seems to parallel type 1 G-NEN. In the setting of metastatic disease, which can occur in any subtype but is most common by far in type 3 G-NEN, the lack of trial data unique to G-NEN results in extrapolation of strategies and agents for treatment of non-gastric neuroendocrine disease. The rapid pace of development in this area is likely to benefit the metastatic G-NEN patient as well. As treatment is predicate on type of G-NEN, establishing the etiology of the lesion is crucial but growing knowledge of G-NEN pathophysiology and close collaboration between pathologists, gastroenterologists, radiologists, surgeons, and oncologists have enabled a growing trend towards de-escalation and less-invasive treatment paradigms.
Collapse
Affiliation(s)
- John W Kunstman
- Department of Surgery, Division of Surgical Oncology, Yale School of Medicine, New Haven, CT, USA
- VA Connecticut Healthcare System, West Haven, CT, USA
| | - Anil Nagar
- Department of Medicine, Division of Gastroenterology, Yale School of Medicine, New Haven, CT, USA
| | - Joanna Gibson
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | - Pamela L Kunz
- Department of Medicine, Section of Medical Oncology, Yale School of Medicine, 25 York Street, New Haven, CT, 06510, USA.
| |
Collapse
|
|
4
|
Liu L, Liu W, Jia Z, Li Y, Wu H, Qu S, Zhu J, Liu X, Xu C. Application of machine learning algorithms to predict lymph node metastasis in gastric neuroendocrine neoplasms. Heliyon 2023; 9:e20928. [PMID: 37928390 PMCID: PMC10622622 DOI: 10.1016/j.heliyon.2023.e20928] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 10/09/2023] [Accepted: 10/11/2023] [Indexed: 11/07/2023] Open
Abstract
Background Neuroendocrine neoplasms (NENs) are tumors that originate from secretory cells of the diffuse endocrine system and typically produce bioactive amines or peptide hormones. This paper describes the development and validation of a predictive model of the risk of lymph node metastasis among gastric NEN patients based on machine learning platform. Methods In this investigation, data from 1256 patients were used, of whom 119 patients from the First Affiliated Hospital of Soochow University in China and 1137 cases from the surveillance epidemiology and end results (SEER) database were combined. Six machine learning algorithms, including the logistic regression model (LR), random forest (RF), decision tree (DT), Naive Bayes (NB), support vector machine (SVM), and k-nearest neighbor algorithm (KNN), were used to build the predictive model. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results Among the 1256 patients with gastric NENs, 276 patients (21.97 %) developed lymph node metastasis. T stage, tumor size, degree of differentiation, and sex were predictive factors of lymph node metastasis. The RF model achieved the best predictive performance among the six machine learning models, with an AUC, accuracy, sensitivity, and specificity of 0.81, 0.78, 0.76, and 0.82, respectively. Conclusion The RF model provided the best prediction and can help physicians determine the lymph node metastasis risk of gastric NEN patients to formulate individualized medical strategies.
Collapse
Affiliation(s)
- Lu Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Wen Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhenyu Jia
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yao Li
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Hongyu Wu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Shuting Qu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jinzhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiaolin Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chunfang Xu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China
| |
Collapse
|
|
5
|
Laffi A, Lania AGA, Ragni A, Di Vito V, Liccardi A, Rubino M, Sesti F, Colao A, Faggiano A. Gastric Neuroendocrine Tumors (g-NETs): A Systematic Review of the Management and Outcomes of Type 3 g-NETs. Cancers (Basel) 2023; 15:cancers15082202. [PMID: 37190131 DOI: 10.3390/cancers15082202] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 04/04/2023] [Accepted: 04/06/2023] [Indexed: 05/17/2023] Open
Abstract
PURPOSE to collect data from real-life experiences of the management of type 3 g-NETs and identify possible prognostic factors that may impact the decision-making process. METHODS We performed a systematic review of the literature on type 3 g-NET management using the PubMed, MEDLINE, and Embase databases. We included cohort studies, case series, and case reports written in the English language. RESULTS We selected 31 out of 556 articles from between 2001 and 2022. In 2 out of the 31 studies, a 10 mm and 20 mm cut-off size were respectively associated with a higher risk of gastric wall infiltration and/or lymph node and distant metastasis at diagnosis. The selected studies reported a higher risk of lymph node or distant metastasis at diagnosis in the case of muscularis propria infiltration or beyond, irrespective of the dimensions or grading. From these findings, size, grading, and gastric wall infiltration seem to be the most relevant factors in management staff making choices and prognoses of type 3 g-NET patients. We produced a hypothetical flowchart for a standardized approach to these rare diseases. CONCLUSION Further prospective analyses are needed to validate the prognostic impact of the use of size, grading, and gastric wall infiltration as prognostic factors in the management of type 3 g-NETs.
Collapse
Affiliation(s)
- Alice Laffi
- Hematology and Oncology, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Andrea Gerardo Antonio Lania
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy
- Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Alberto Ragni
- Endocrinologia e Malattie Metaboliche, AO SS Antonio e Biagio e Cesare Arrigo, Via Venezia, 16, 15121 Alessandria, Italy
| | - Valentina Di Vito
- Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy
| | - Alessia Liccardi
- Operative Unit of Endocrinology, Department of Clinical Medicine and Surgery, Andrology and Diabetology, Federico II University of Naples, 80131 Naples, Italy
| | - Manila Rubino
- Servizio di Endocrinologia Oncologica, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 435, 20141 Milan, Italy
| | - Franz Sesti
- Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, Italy
| | - Annamaria Colao
- Endocrinology Unit, Department of Clinical Medicine and Surgery, University Federico II, 80126 Naples, Italy
- UNESCO "Education for Health and Sustainable Development", Federico II University, 80131 Naples, Italy
| | - Antongiulio Faggiano
- Endocrinology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, ENETS Center of Excellence, Sapienza University of Rome, 00185 Rome, Italy
| |
Collapse
|
|
6
|
Gastric neuroendocrine neoplasms: a primer for radiologists. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:3993-4004. [PMID: 35411433 DOI: 10.1007/s00261-022-03509-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/22/2022] [Accepted: 03/23/2022] [Indexed: 01/18/2023]
Abstract
Gastric neuroendocrine neoplasms are uncommon tumors with variable differentiation and malignant potential. Three main subtypes are recognized: type 1, related to autoimmune atrophic gastritis; type 2, associated with Zollinger-Ellison and MEN1 syndrome; and type 3, sporadic. Although endoscopy alone is often sufficient for diagnosis and management of small, indolent, multifocal type 1 tumors, imaging is essential for evaluation of larger, high-grade, and type 2 and 3 neoplasms. Hypervascular intraluminal gastric masses are typically seen on CT/MRI, with associated perigastric lymphadenopathy and liver metastases in advanced cases. Somatostatin receptor nuclear imaging (such as Ga-68-DOTATATE PET/CT) may also be used for staging and assessing candidacy for peptide receptor radionuclide therapy. Radiotracer uptake is more likely in well-differentiated, lower-grade tumors, and less likely in poorly differentiated tumors, for which F-18-FDG-PET/CT may have additional value. Understanding disease pathophysiology and evolving histologic classifications is particularly useful for radiologists, as these influence tumor behavior, preferred imaging, therapy options, and patient prognosis.
Collapse
|
|
7
|
Metastasis Prevalence and Survival of Patients with T1-2 Gastric Neuroendocrine Tumor Treated with Endoscopic Therapy and Surgery. Dig Dis Sci 2022; 67:3228-3238. [PMID: 34272627 DOI: 10.1007/s10620-021-07143-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 06/21/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND AIM The selection criteria and long-term outcomes of endoscopic therapy (ET) for gastric neuroendocrine tumors (G-NETs) remain controversial. METHODS Using Surveillance, Epidemiology, and End Results (SEER) Program database, we assessed the prevalence of metastasis of early G-NETs and long-term outcomes of ET in G-NET patients with good/moderate differentiation and no muscularis propria (MP) involvement. RESULTS A total of 2207 patients with stage T1 and T2 G-NETs were included. The depth of invasion into MP [odds ratio (OR) 4.581, 95% confidence interval (CI) 2.571-8.162; P < 0.001] and size of > 20 mm (OR 5.656, 95% CI 2.002-15.975; P = 0.001) were significantly associated with metastasis. The 5-year overall survival (OS) and cancer-specific survival (CSS) of the ET group were similar to the surgery group (91.11% vs. 91.09%, P = 0.750; 99.26% vs. 99.01%, P = 0.173). In the multivariable Cox proportional hazards regression models adjusting for age, gender, race, year of diagnosis, SEER region, depth of tumor invasion, site of cancer, tumor size, and chemotherapy, procedures employed (ET or surgery) had no significant impact on the OS [hazard ratio (HR) 1.189; 95%CI 0.721-1.961; P = 0.498] and CSS (HR 0.684; 95% CI 0.021-22.727; P = 0.832). CONCLUSIONS The long-term outcome of survival did not appear to differ between ET and surgery in G-NETs with good/moderate differentiation, ≤ 20 mm size, and no MP involvement.
Collapse
|
|
8
|
Dai M, Mullins CS, Lu L, Alsfasser G, Linnebacher M. Recent advances in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Surg 2022; 14:383-396. [PMID: 35734622 PMCID: PMC9160679 DOI: 10.4240/wjgs.v14.i5.383] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/17/2022] [Accepted: 04/29/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a rare group of tumors originating from neuroendocrine cells of the digestive system. Their incidence has increased over the last decades. The specific pathogenetic mechanisms underlying GEP-NEN development have not been completely revealed. Unfunctional GEP-NENs are usually asymptomatic; some grow slowly and thus impede early diagnosis, which ultimately results in a high rate of misdiagnosis. Therefore, many GEP-NEN patients present with later staged tumors. Motivated hereby, research attention for diagnosis and treatment for GEP-NENs increased in recent years. The result of which is great progress in clinical diagnosis and treatment. According to the most recent clinical guidelines, improved grading standards can accurately define poorly differentiated grade 3 neuroendocrine tumors and neuroendocrine carcinomas (NECs), which are subclassified into large and small cell NECs. Combining different functional imaging methods facilitates precise diagnosis. The expression of somatostatin receptors helps to predict prognosis. Genetic analyses of mutations affecting death domain associated protein (DAXX), multiple endocrine neoplasia type 1 (MEN 1), alpha thalassemia/intellectual disability syndrome X-linked (ATRX), retinoblastoma transcriptional corepressor 1 (RB 1), and mothers against decapentaplegic homolog 4 (SMAD 4) help distinguishing grade 3 NENs from poorly differentiated NECs. The aim of this review is to summarize the latest research progress on diagnosis and treatment of GEP-NENs.
Collapse
Affiliation(s)
- Meng Dai
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Christina S Mullins
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Lili Lu
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| | - Guido Alsfasser
- Clinic of General Surgery, Rostock University Medical Center, 18057 Rostock, Germany
| | - Michael Linnebacher
- Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany
| |
Collapse
|
|
9
|
Canakis A, Lee LS. Current updates and future directions in diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms. World J Gastrointest Endosc 2022; 14:267-290. [PMID: 35719897 PMCID: PMC9157694 DOI: 10.4253/wjge.v14.i5.267] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/14/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms are a heterogenous group of rare neoplasms that are increasingly being discovered, often incidentally, throughout the gastrointestinal tract with varying degrees of activity and malignant potential. Confusing nomenclature has added to the complexity of managing these lesions. The term carcinoid tumor and embryonic classification have been replaced with gastroenteropancreatic neuroendocrine neoplasm, which includes gastrointestinal neuroendocrine and pancreatic neuroendocrine neoplasms. A comprehensive multidisciplinary approach is important for clinicians to diagnose, stage and manage these lesions. While histological diagnosis is the gold standard, recent advancements in endoscopy, conventional imaging, functional imaging, and serum biomarkers complement histology for tailoring specific treatment options. In light of developing technology, our review sets out to characterize diagnostic and therapeutic advancements for managing gastroenteropancreatic neuroendocrine tumors, including innovations in radiolabeled peptide imaging, circulating biomarkers, and endoscopic treatment approaches adapted to different locations throughout the gastrointestinal system.
Collapse
Affiliation(s)
- Andrew Canakis
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
| | - Linda S Lee
- Division of Gastroenterology Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
| |
Collapse
|
|
10
|
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: 6] [Impact Index Per Article: 2.0] [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.
Collapse
Affiliation(s)
| | | | | | | | | | - Haixing Ju
- *Correspondence: Yuping Zhu, ; Haixing Ju,
| | - Yuping Zhu
- *Correspondence: Yuping Zhu, ; Haixing Ju,
| |
Collapse
|
|
11
|
Yang T, Fong ZV, Pak L, Wang SJ, Wei J, Wang J. A Modified T-stage Classification for Gastric Neuroendocrine Tumors. J Surg Res 2021; 270:486-494. [PMID: 34800795 DOI: 10.1016/j.jss.2021.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 10/07/2021] [Accepted: 10/11/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND The eighth edition of the American Joint Committee on Cancer (AJCC) staging manual's TNM staging classification for gastric neuroendocrine tumors has been shown to have poor prognostic discriminability. The aim of present study was to propose a modified T-stage classification, and externally validate its performance in a separate population data registry. METHODS A modified T-stage classification with tumor size and extent of tumor invasion was generated from the National Cancer Database between 2004 and 2014 (n = 1249). External validation was performed using the Surveillance, Epidemiology, and End Results registry between 1973 and 2013 (n = 539). RESULTS In the National Cancer Database population, using the AJCC T-stage classification, the 5-y survival rates were 85.7%, 80.8%, 64.5%, and 46.1% in T1, T2, T3, and T4 patients respectively (P < 0.001). These rates were more contrasting with the modified T-stage (mT) classification at 87.0%, 78.2%, 59.0%, and 40.3% respectively (P < 0.001). When patients within each of the AJCC T stages were stratified by mT stages, significant survival heterogeneity was observed within each of the AJCC T2 to T4 stages (P < 0.01). Conversely, when mT stages were stratified by AJCC T stage, no survival difference was observed in any of the mT stages (P > 0.05). The same analyses were performed using Surveillance, Epidemiology, and End Results data, and all the observed results were validated. CONCLUSION The current AJCC T stage classification categorizes patients into groups with heterogenous prognosis, thus failing to serve as an effective staging tool. A modified T-stage classification demonstrated significantly improved stratification for patients with gastric neuroendocrine tumors.
Collapse
Affiliation(s)
- Tingsong Yang
- Department of General Surgery, Shanghai Tenth Peoples' Hospital, Tongji University of Medicine, Shanghai
| | - Zhi Ven Fong
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts
| | - Linda Pak
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts
| | - Shengnan J Wang
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts
| | - Jia Wei
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts
| | - Jiping Wang
- Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
| |
Collapse
|
|
12
|
Feng H, Zheng J, Zheng C, Deng Z, Liao Q, Wang J, Li Y. The probability of Lymph node metastasis with a tumor size larger than and smaller than 4 cm is different in stages T1-T3 of Siewert type II adenocarcinoma of esophagogastric junction: A Population-Based Study. J Cancer 2021; 12:6873-6882. [PMID: 34659575 PMCID: PMC8518009 DOI: 10.7150/jca.63392] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 09/12/2021] [Indexed: 11/23/2022] Open
Abstract
Background: In adenocarcinoma of esophagogastric junction (AEG), the relationship between tumor size (TS) and lymph node metastasis (LNM) is unclear. This study aimed to explore the relationship between TS and LNM, and to construct a prediction model for LNM. Materials and Methods: Data from 4649 Siewert type II AEG patients were retrospectively acquired from the Surveillance, Epidemiology, and End Result (SEER) database. TS data was analyzed as a continuous variable, but also divided into 1-cm-interval categorical groups for further analysis. The logistic regression model and restricted cubic spline (RCS) model was used to explore the relationship between TS and LNM, after adjusting for covariates. Internal validations as well as external validation (Single-Center data) were used to check our LNM prediction model. Results: TS and LNM showed a significant relationship in the logistic regression analysis, regardless of the TS data being entered as a continuous or a categorical variable, after adjusting for covariates. The logistic regression model and RCS consistently showed that larger TS resulted in larger Odds Ratio (OR) values. When tumors were larger than 4 cm, the OR value remained relatively constant. The receiver operator characteristic curve evaluated the nomogram by the area under the curve (AUC) (AUC=0.737, in internal validation; AUC=0.626, in external validation), and the calibration curve of the nomogram showed an improved prediction system. Conclusions: In Siewert type II T1-T3 stage AEG patients, we reported that LNM increased with TS up to 4-cm, and our nomogram provided a simple tool to predict LNM.
Collapse
Affiliation(s)
- Huolun Feng
- Department of gastrointestinal surgery, Guangdong Provincial People's Hospital; Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P. R. China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, P. R. China
| | - Jiabin Zheng
- Department of gastrointestinal surgery, Guangdong Provincial People's Hospital; Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P. R. China
| | - Chengbin Zheng
- Department of gastrointestinal surgery, Guangdong Provincial People's Hospital; Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P. R. China
| | - Zhenru Deng
- Department of gastrointestinal surgery, Guangdong Provincial People's Hospital; Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P. R. China
| | - Qianchao Liao
- Department of gastrointestinal surgery, Guangdong Provincial People's Hospital; Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P. R. China
| | - Junjiang Wang
- Department of gastrointestinal surgery, Guangdong Provincial People's Hospital; Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P. R. China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, P. R. China
| | - Yong Li
- Department of gastrointestinal surgery, Guangdong Provincial People's Hospital; Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P. R. China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, P. R. China
| |
Collapse
|
|
13
|
Noh JH, Kim DH, Yoon H, Hsing LC, Na HK, Ahn JY, Lee JH, Jung KW, Choi KD, Song HJ, Lee GH, Jung HY. Clinical Outcomes of Endoscopic Treatment for Type 1 Gastric Neuroendocrine Tumor. J Gastrointest Surg 2021; 25:2495-2502. [PMID: 33825119 DOI: 10.1007/s11605-021-04997-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 03/23/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although the rate of early detection and endoscopic treatment of gastric neuroendocrine tumors (NETs) is steadily increasing, there are insufficient studies on the long-term outcomes of endoscopic treatment. Therefore, we aimed to investigate the clinical features and long-term outcomes of endoscopic treatment for type 1 gastric NETs. METHODS Subjects who underwent endoscopic treatment for gastric NETs between March 1997 and December 2015 were included. Clinical features and endoscopic treatment outcomes were retrospectively investigated by reviewing medical records. RESULTS In total, 125 subjects underwent endoscopic treatment including forceps biopsy (n = 21), argon plasma coagulation (n = 1), endoscopic mucosal resection (EMR, n = 62), and endoscopic submucosal dissection (ESD, n = 41). In total, 103 patients with 114 lesions, who underwent EMR or ESD, were analyzed to evaluate endoscopic and oncologic outcomes. The rates of en bloc resection in the EMR and ESD groups were 91.5% and 97.7%, respectively. Complete resection rates were significantly higher in the ESD group than in the EMR group; it was also higher in < 1-cm small-sized lesions than in 1-2-cm large-sized lesions. Adverse events were similar between the two groups. During a median follow-up period of 63 months, local recurrence rates were 6.5% and 2.4% in the EMR and ESD groups, respectively, and the disease-free survival rate did not differ significantly between the groups. CONCLUSION Endoscopic treatment for type 1 gastric NETs less than 2 cm in diameter and confined to mucosal and submucosal layers could be an effective and safe treatment strategy based on the favorable long-term outcome.
Collapse
Affiliation(s)
- Jin Hee Noh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
| | - Hwan Yoon
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Li-Chang Hsing
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Kyong Na
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Don Choi
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho June Song
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gin Hyug Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| |
Collapse
|
|
14
|
Shah SC, Piazuelo MB, Kuipers EJ, Li D. AGA Clinical Practice Update on the Diagnosis and Management of Atrophic Gastritis: Expert Review. Gastroenterology 2021; 161:1325-1332.e7. [PMID: 34454714 PMCID: PMC8740554 DOI: 10.1053/j.gastro.2021.06.078] [Citation(s) in RCA: 241] [Impact Index Per Article: 60.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 06/09/2021] [Accepted: 06/28/2021] [Indexed: 02/07/2023]
Abstract
DESCRIPTION The purpose of this Clinical Practice Update Expert Review is to provide clinicians with guidance on the diagnosis and management of atrophic gastritis, a common preneoplastic condition of the stomach, with a primary focus on atrophic gastritis due to chronic Helicobacter pylori infection-the most common etiology-or due to autoimmunity. To date, clinical guidance for best practices related to the diagnosis and management of atrophic gastritis remains very limited in the United States, which leads to poor recognition of this preneoplastic condition and suboptimal risk stratification. In addition, there is heterogeneity in the definitions of atrophic gastritis, autoimmune gastritis, pernicious anemia, and gastric neoplasia in the literature, which has led to confusion in clinical practice and research. Accordingly, the primary objective of this Clinical Practice Update is to provide clinicians with a framework for the diagnosis and management of atrophic gastritis. By focusing on atrophic gastritis, this Clinical Practice Update is intended to complement the 2020 American Gastroenterological Association Institute guidelines on the management of gastric intestinal metaplasia. These recent guidelines did not specifically discuss the diagnosis and management of atrophic gastritis. Providers should recognize, however, that a diagnosis of intestinal metaplasia on gastric histopathology implies the diagnosis of atrophic gastritis because intestinal metaplasia occurs in underlying atrophic mucosa, although this is often not distinctly noted on histopathologic reports. Nevertheless, atrophic gastritis represents an important stage with distinct histopathologic alterations in the multistep cascade of gastric cancer pathogenesis. METHODS The Best Practice Advice statements presented herein were developed from a combination of available evidence from published literature and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out. These statements are meant to provide practical advice to clinicians practicing in the United States. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Atrophic gastritis is defined as the loss of gastric glands, with or without metaplasia, in the setting of chronic inflammation mainly due to Helicobacter pylori infection or autoimmunity. Regardless of the etiology, the diagnosis of atrophic gastritis should be confirmed by histopathology. BEST PRACTICE ADVICE 2: Providers should be aware that the presence of intestinal metaplasia on gastric histology almost invariably implies the diagnosis of atrophic gastritis. There should be a coordinated effort between gastroenterologists and pathologists to improve the consistency of documenting the extent and severity of atrophic gastritis, particularly if marked atrophy is present. BEST PRACTICE ADVICE 3: Providers should recognize typical endoscopic features of atrophic gastritis, which include pale appearance of gastric mucosa, increased visibility of vasculature due to thinning of the gastric mucosa, and loss of gastric folds, and, if with concomitant intestinal metaplasia, light blue crests and white opaque fields. Because these mucosal changes are often subtle, techniques to optimize evaluation of the gastric mucosa should be performed. BEST PRACTICE ADVICE 4: When endoscopic features of atrophic gastritis are present, providers should assess the extent endoscopically. Providers should obtain biopsies from the suspected atrophic/metaplastic areas for histopathological confirmation and risk stratification; at a minimum, biopsies from the body and antrum/incisura should be obtained and placed in separately labeled jars. Targeted biopsies should additionally be obtained from any other mucosal abnormalities. BEST PRACTICE ADVICE 5: In patients with histology compatible with autoimmune gastritis, providers should consider checking antiparietal cell antibodies and anti-intrinsic factor antibodies to assist with the diagnosis. Providers should also evaluate for anemia due to vitamin B-12 and iron deficiencies. BEST PRACTICE ADVICE 6: All individuals with atrophic gastritis should be assessed for H pylori infection. If positive, treatment of H pylori should be administered and successful eradication should be confirmed using nonserological testing modalities. BEST PRACTICE ADVICE 7: The optimal endoscopic surveillance interval for patients with atrophic gastritis is not well-defined and should be decided based on individual risk assessment and shared decision making. A surveillance endoscopy every 3 years should be considered in individuals with advanced atrophic gastritis, defined based on anatomic extent and histologic grade. BEST PRACTICE ADVICE 8: The optimal surveillance interval for individuals with autoimmune gastritis is unclear. Interval endoscopic surveillance should be considered based on individualized assessment and shared decision making. BEST PRACTICE ADVICE 9: Providers should recognize pernicious anemia as a late-stage manifestation of autoimmune gastritis that is characterized by vitamin B-12 deficiency and macrocytic anemia. Patients with a new diagnosis of pernicious anemia who have not had a recent endoscopy should undergo endoscopy with topographical biopsies to confirm corpus-predominant atrophic gastritis for risk stratification and to rule out prevalent gastric neoplasia, including neuroendocrine tumors. BEST PRACTICE ADVICE 10: Individuals with autoimmune gastritis should be screened for type 1 gastric neuroendocrine tumors with upper endoscopy. Small neuroendocrine tumors should be removed endoscopically, followed by surveillance endoscopy every 1-2 years, depending on the burden of neuroendocrine tumors. BEST PRACTICE ADVICE 11: Providers should evaluate for iron and vitamin B-12 deficiencies in patients with atrophic gastritis irrespective of etiology, especially if corpus-predominant. Likewise, in patients with unexplained iron or vitamin B-12 deficiency, atrophic gastritis should be considered in the differential diagnosis and appropriate diagnostic evaluation pursued. BEST PRACTICE ADVICE 12: In patients with autoimmune gastritis, providers should recognize that concomitant autoimmune disorders, particularly autoimmune thyroid disease, are common. Screening for autoimmune thyroid disease should be performed.
Collapse
Affiliation(s)
- Shailja C. Shah
- Gastroenterology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California,Division of Gastroenterology, University of California, San Diego, La Jolla, California
| | - M. Blanca Piazuelo
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Ernst J. Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Dan Li
- Department of Gastroenterology, Kaiser Permanente Northern California, Santa Clara, California,Division of Research, Kaiser Permanente Northern California, Oakland, California
| |
Collapse
|
|
15
|
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.
Collapse
|
|
16
|
Hanna A, Kim-Kiselak C, Tang R, Metz DC, Yang Z, DeMatteo R, Fraker DL, Roses RE. Gastric Neuroendocrine Tumors: Reappraisal of Type in Predicting Outcome. Ann Surg Oncol 2021; 28:8838-8846. [PMID: 34120268 DOI: 10.1245/s10434-021-10293-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/25/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Type I gastric neuroendocrine tumors (GNETs) are typically managed either expectantly or endoscopically. In contrast, locoregional surgery has been recommended for patients with type III GNETs because of the risk of metastasis. This study aimed to identify predictors of outcome independent of type in a contemporary cohort of GNET patients. METHODS A single-institution retrospective cohort study of 121 patients with a pathologic diagnosis of primary GNET between January 2009 and June 2019 was performed. GNETs were designated as type 1 (n = 74) if atrophic gastritis was present, or as type III (n = 47) in the absence of atrophic gastritis. Demographic, clinical, and histopathologic factors were examined using Kaplan-Meier and multivariable Cox regression to assess the impact of various factors on recurrence and overall survival. RESULTS Median follow-up for the entire cohort was 62.7 months. While there was no difference in OS in patients with different GNET types (p = 0.10), higher tumor grade (p = 0.02) and presence of nodal or distant metastases (p = 0.02) predicted worse survival on multivariable analysis. Among type III GNET patients, those with small (< 0.5 cm), grade 1 lesions ("low-risk") were less likely to develop metastases (0% versus 33%, p < 0.01) and more likely to survive (100% versus 67%, p < 0.01) at 5 years. CONCLUSIONS Size and tumor grade predict recurrence and survival in patients with GNETs irrespective of type. Small, low-grade type III GNETs are associated with minimal risk of progression and may be managed accordingly.
Collapse
Affiliation(s)
- Andrew Hanna
- Department of General Surgery, University of Pennsylvania, Philadelphia, PA, USA.
| | | | - Rebecca Tang
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - David C Metz
- Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Zhaohai Yang
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Ronald DeMatteo
- Department of General Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Douglas L Fraker
- Department of General Surgery, University of Pennsylvania, Philadelphia, PA, USA
| | - Robert E Roses
- Department of General Surgery, University of Pennsylvania, Philadelphia, PA, USA
| |
Collapse
|
|
17
|
Sivandzadeh GR, Ejtehadi F, Shoaee S, Aminlari L, Niknam R, Taghavi AR, Geramizadeh B, Hormati A, Safarpour AR, Bagheri Lankarani K. Endoscopic mucosal resection: still a reliable therapeutic option for gastrointestinal neuroendocrine tumors. BMC Gastroenterol 2021; 21:238. [PMID: 34030644 PMCID: PMC8142474 DOI: 10.1186/s12876-021-01821-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 05/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neuroendocrine tumors (NETs), as a rare and heterogeneous category of solid tumors, feature various morphologies and behaviors. In recent years, the incidence of NETs has continued to increase. Endoscopic mucosal resection (EMR) is one of the therapeutic modalities for the treatment of gastric and rectal NETs. METHODS We evaluated patients with well-differentiated NETs of the stomach, duodenum, or rectum between 2011 and 2018. In this study, all cases with tumors confined to the mucosal or submucosal layers and smaller than 20 mm were resected using the EMR technique. We used EUS, CT scan, or MRI to exclude patients with advanced disease. All patients were actively monitored for recurrence according to the recommended protocols. RESULTS A total of 36 patients with NETs entered the study; 17 (47.2%) were female and the remaining 19 (52.8%) were male, with a total age range of 20-74 years (mean: 52.47 ± 13.47 years). Among the tumors, 31 cases (86.1%) were G1 and the remaining 5 (13.9%) were G2. Based on the pathology reports, 22 tumors (61.1%) were smaller than 1 cm, while the remaining 14 (38.9%) were between 1-2 cm. Twenty-two patients (61.1%) had a margin of specimen involved with the tumor. No recurrence was observed during the mean follow-up time of 63.5 ± 19.8 months (range: 39-103 months). All 36 cases survived during the study period. CONCLUSION Conventional EMR procedure provides low chance of R0 (complete resection) achievement in gastrointestinal NETs smaller than 20 mm and limited to the mucosa or sub mucosa. However, it could be an option if patients are closely followed. Postoperative marginal involvement is not a reliable predictor of disease recurrence, which may be explained by the deleterious effect of heat coagulation and cauterization applied during tumor removal.
Collapse
Affiliation(s)
- Gholam Reza Sivandzadeh
- Department of Internal Medicine, Gastroenterohepatology Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Fars Iran
| | - Fardad Ejtehadi
- Department of Internal Medicine, Gastroenterohepatology Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Fars Iran
| | - Shima Shoaee
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Fars Iran
| | - Ladan Aminlari
- Gastroentrohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Fars Iran
| | - Ramin Niknam
- Department of Internal Medicine, Gastroenterohepatology Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Fars Iran
| | - Ali Reza Taghavi
- Department of Internal Medicine, Gastroenterohepatology Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Fars Iran
| | - Bita Geramizadeh
- Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Fars Iran
| | - Ahmad Hormati
- Gastrointestinal and Liver Diseases Research Center, Iran University of Medical Sciences, Firozgar Hospital, Tehran, Iran
| | - Ali Reza Safarpour
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Kamran Bagheri Lankarani
- Health Policy Research Center, School of Medicine, Institute of Health, Shiraz University of Medical Sciences, Building No. 2, Eighth Floor, Zand Avenue, 71345-1414 Shiraz, Fars Iran
| |
Collapse
|
|
18
|
Panzuto F, Magi L, Esposito G, Rinzivillo M, Annibale B. Comparison of Endoscopic Techniques in the Management of Type I Gastric Neuroendocrine Neoplasia: A Systematic Review. Gastroenterol Res Pract 2021; 2021:1-6. [PMID: 33859684 PMCID: PMC8026302 DOI: 10.1155/2021/6679397] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/09/2021] [Accepted: 03/17/2021] [Indexed: 02/08/2023] Open
Abstract
Background. Endoscopic resection is considered the treatment of choice for type I gastric neuroendocrine neoplasia (gNEN) given its indolent behaviour; however, the favoured endoscopic technique to remove these tumours is not well established. Aims. This systematic review is aimed at investigating the best endoscopic management for type I gNEN. Methods. PubMed Central/Medline and Scopus were systematically searched for records up to August 31, 2020. Results. After screening the 675 retrieved records, 6 studies were selected for the final analysis. The main endoscopic resection techniques described were endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Overall, 112 gNENs were removed by EMR and 77 by ESD. Both techniques showed similar results for complete and en bloc resection (97.4% and 98.7%; 92.3% and 96.3% with ESD and EMR, respectively). ESD was associated with a higher rate of complications than EMR (11.7% vs. 5.4%), but this difference was not statistically significant (
). The rates of recurrence during follow-up were 18.2% and 11.5% for EMR and ESD, respectively. Conclusions. To date, there are no sufficient data showing superiority of a given endoscopic technique over others. Both ESD and EMR seem to be effective in the management of type I gNEN, with a relatively low rate of recurrence.
Collapse
Affiliation(s)
- Francesco Panzuto
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Ludovica Magi
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
- Department of Translational and Precision Medicine, Sapienza University of Rome, Italy
| | - Gianluca Esposito
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Italy
| | - Maria Rinzivillo
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Bruno Annibale
- Digestive Disease Unit, Sant’Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Italy
| |
Collapse
|
|
19
|
Hirasawa T, Yamamoto N, Sano T. Is endoscopic resection appropriate for type 3 gastric neuroendocrine tumors? Retrospective multicenter study. Dig Endosc 2021; 33:408-417. [PMID: 32578248 DOI: 10.1111/den.13778] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 06/12/2020] [Accepted: 06/16/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND Gastrectomy with lymphadenectomy is recommended for type 3 gastric neuroendocrine tumors (G-NETs). This study aimed to identify the risk factors for lymph node metastasis (LNM) arising from G-NETs to assess the suitability of endoscopic resection (ER). METHODS Nationwide clinicopathological data of patients with type 3 G-NETs who underwent surgery or ER were collected. A single pathologist graded the histological tumor specimens. RESULTS Among 176 cases from 53 institutions, 144 were eligible for analysis (90 NET-G1 and 54 NET-G2 grade, 8-mm median-size tumors). Of these, 63 patients had undergone ER (15 with additional surgeries). Histological data regarding LNM were available for 93 surgical patients. LNM was confirmed in 15 (16%) tumors and was correlated with tumor diameter, invasion depth, and tumor grade. LNM was negative in six tumors ≤5 mm, confined to the mucosa or submucosa, with a grade of G1, and without lymphovascular invasion, but the number of cases was too small to propose ER indications. Among 48 patients treated with ER alone, only one developed recurrence; no mortality was observed at follow-up, although many patients were classified with SM2/NET-G2/tumors >5 mm. This suggests that not all LNMs arising from small G-NETs are fatal. CONCLUSION Gastrectomy with lymphadenectomy for type 3 G-NETs is recommended on the basis of LNM. However, ER for type 3 G-NETs ≤10 mm, confined to the mucosa or submucosa, with a grade of G1 has shown excellent survival outcomes despite the risk of LNM, and therefore, could be an alternative treatment option.
Collapse
Affiliation(s)
- Toshiaki Hirasawa
- Departments of, Department of, Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Noriko Yamamoto
- Department of, Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Sano
- Department of, Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| |
Collapse
|
|
20
|
Dhruv S, Anwar S, Polavarapu A, Liliane D. Gastric Carcinoid: The Invisible Tumor! Cureus 2021; 13:e13556. [PMID: 33791175 PMCID: PMC8004355 DOI: 10.7759/cureus.13556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Neuroendocrine tumor (NET) of the stomach or gastric carcinoid (GC) is a rare tumor derived from enterochromaffin-like (ECL) cells of the stomach and is more common in women after the fifth decade of life. The incidence of GC has been recently trending up. While most GC are visible lesions upon direct visualization on endoscopy, one-fourth of these tumors are intramucosal and not readily identified on upper endoscopy. Thus, a complete gastric map with biopsies of antrum, body, and fundus is required to confirm the presence of carcinoid growth. Herein we report a rare case of GC which was identified on a random gastric biopsy specimen.
Collapse
Affiliation(s)
- Samyak Dhruv
- Internal Medicine, Northwell Health, New York, USA
| | | | | | - Deeb Liliane
- Gatsroenterology, Northwell Health, New York, USA
| |
Collapse
|
|
21
|
Ramai D, Singh J, Barakat M, Chandan S, Adler DG. Rate of lymph node metastasis in patients with T1 gastric carcinoid tumors. Eur J Gastroenterol Hepatol 2021; 32:302-303. [PMID: 33369959 DOI: 10.1097/meg.0000000000001900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Daryl Ramai
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn
| | - Jameel Singh
- Department of Medicine, Mather Hospital, Port Jefferson
| | - Mohamed Barakat
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Brooklyn, New York
| | - Saurabh Chandan
- Division of Gastroenterology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Douglas G Adler
- Division of Gastroenterology and Hepatology, University of Utah School of Medicine, Huntsman Cancer Center, Salt Lake City, Utah, USA
| |
Collapse
|
|
22
|
Wang J, Doherty G. Neuroendocrine Tumors: Stomach. ENDOCRINE SURGERY COMPREHENSIVE BOARD EXAM GUIDE 2021:661-679. [DOI: 10.1007/978-3-030-84737-1_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
23
|
Abstract
PURPOSE OF REVIEW Gastroesophageal neuroendocrine neoplasms (NENs) are a rare entity. Recent 2019 WHO classifications reflect our understanding of tumor biology, namely, that distinct molecular characteristics underline tumor behavior and prognosis. Here, we reviewed the evidence for linking molecular findings with the clinicopathological features and treatment of gastroesophageal NENs. RECENT FINDINGS Degree of differentiation and Ki-67 proliferation index are required for accurate classification of neuroendocrine tumors and carcinomas but not sufficient to distinguish between the two entities. Resection remains the mainstay treatment for early-stage gastroesophageal neuroendocrine tumors. Additional perioperative therapy may benefit mitotically active tumors. There is a role for somatostatin analogues, especially in the setting of metastatic and symptomatic disease. New radiolabeled somatostatin analogues, immunotherapy, and embolization offer multimodality treatments for distant metastases. We need to understand the specific underlying biology of the various subtypes of gastroesophageal NENs to provide tailored treatment.
Collapse
|
|
24
|
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%).
Collapse
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
| |
Collapse
|
|
25
|
Naito S, Naito M, Yamamoto N, Kume T, Hosino S, Kinjyo Y, Naito Y, Naito H, Hasegawa S. Polypoid gallbladder neuroendocrine tumor diagnosed as benign polyp before surgery: A case report. Mol Clin Oncol 2019; 12:225-229. [PMID: 32064098 PMCID: PMC7017218 DOI: 10.3892/mco.2019.1971] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 11/25/2019] [Indexed: 01/24/2023] Open
Abstract
Gallbladder neuroendocrine tumors (GB-NETs) comprise only 0.5% of all NET cases, and their biology has been incompletely characterized. In the present study we report the case of a 50-year-old male patient with GB-NET who was admitted to Naito Hospital with diarrhea as the main complaint. At initial diagnosis, serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were within the normal range. Abdominal ultrasonography and contrast-enhanced computed tomography (CT) revealed gallbladder adenomyomatosis and cholecystitis, and an 8-mm pedunculated polypoid lesion was found in the neck of the gallbladder using drip infusion cholecystocholangiography-CT. As it was considered a benign polyp, laparoscopic cholecystectomy was performed. Pathological examination revealed a polypoid lesion that comprised NET cells with a cord-like or ribbon-like arrangement, and the cells exhibited positive immunostaining for chromogranin A and synaptophysin. In addition, immunohistochemical staining showed a Ki-67 index (i.e., proliferation index) of <1%, and no necrosis or mitotic figures were observed in the background. Based on these observations, we diagnosed the following: GB-NET, G1, 10x12 mm in size and located in the gallbladder neck. According to the World Health Organization 2010 classification, NET G1 is a well-differentiated tumor, with the tumor cells having a low proliferative potential [Ki-67 index ≤2%; mitotic figure number <2 (/10 HPF)]. It is regarded as a low- to mild-grade malignancy. Low-grade GB-NET occurs relatively rarely, and no clear guidelines have been formulated regarding its surgical treatment, such as minimal surgical excision margins or lymph node dissection. Detailed treatment recommendations should be developed after systematic studies of additional cases of GB-NET.
Collapse
Affiliation(s)
- Shigetoshi Naito
- Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan.,Naito Hospital, Kurume, Fukuoka 830-0038, Japan
| | | | | | - Tohru Kume
- Naito Hospital, Kurume, Fukuoka 830-0038, Japan
| | | | - Yoshinao Kinjyo
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Yoshiki Naito
- Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | | | - Suguru Hasegawa
- Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan
| |
Collapse
|
|
26
|
Felder S, Jann H, Arsenic R, Denecke T, Prasad V, Knappe-Drzikova B, Maasberg S, Wiedenmann B, Pavel M, Pascher A, Pape UF. Gastric neuroendocrine neoplasias: manifestations and comparative outcomes. Endocr Relat Cancer 2019; 26:751-763. [PMID: 31272081 PMCID: PMC6686747 DOI: 10.1530/erc-18-0582] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 07/04/2019] [Indexed: 12/15/2022]
Abstract
Although gastric neuroendocrine neoplasias (gNEN) are an orphan disease, their incidence is rising. The heterogeneous clinical course powers the ongoing discussion of the most appropriate classification system and management. Prognostic relevance of proposed classifications was retrospectively analysed in 142 patients from a single tertiary referral centre. Baseline, management and survival data were acquired for statistical analyses. The distribution according to the clinicopathological typification was gNEN-1 (n = 86/60.6%), gNEN-2 (n = 7/4.9%), gNEN-3 (n = 24/16.9%) and gNEN-4 (n = 25/17.6%), while hypergastrinemia-associated gNEN-1 and -2 were all low-grade tumours (NET-G1/2), formerly termed sporadic gNEN-3 could be subdivided into gNEN-3 with grade 1 or 2 and gNEN-4 with grade 3 (NEC-G3). During follow-up 36 patients died (25%). The mean overall survival (OS) of all gNEN was 14.2 years. The OS differed statistically significant across all subgroups with either classification system. According to UICC 2017 TNM classification, OS differed for early and advanced stages, while WHO grading indicated poorer prognosis for NEC-G3. Cox regression analysis confirmed the independent prognostic validity of either classification system for survival. Particularly careful analysis of the clinical course of gNEN-1 (ECLomas, gastric carcinoids) confirmed their mostly benign, but recurrent and extremely slowly progressive behaviour with low risk of metastasis (7%) and an efficient long-term control by repetitive endoscopic procedures. Our study provides evidence for the validity of current classifications focusing on typing, grading and staging. These are crucial tools for risk stratification, especially to differentiate gNEN-1 as well as sporadic gNET and gNEC (gNEN-3 vs -4).
Collapse
Affiliation(s)
- S Felder
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - H Jann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - R Arsenic
- Institut für Pathologie, Charité – Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - T Denecke
- Klinik für Radiologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - V Prasad
- Klinik für Nuklearmedizin, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Klinik für Nuklearmedizin, Universitätklinikum Ulm, Ulm, Germany
| | - B Knappe-Drzikova
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - S Maasberg
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany
| | - B Wiedenmann
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - M Pavel
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Medizinische Klinik 1, Gastroenterologie, Pneumologie und Endokrinologie, Universitätsklinikum der Friedrich-Alexander Universität Erlangen, Erlangen, Germany
| | - A Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Uinversitätsklinikum Münster, Münster, Germany
| | - U F Pape
- Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie (einschl. Arbeitsbereich Stoffwechselerkrankungen), Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Innere Medizin und Gastroenterologie, Asklepios Klinik St. Georg, Asklepios Medical School, Hamburg, Germany
- Correspondence should be addressed to U F Pape:
| |
Collapse
|
|
27
|
Aisu Y, Yasukawa D, Kimura Y, Hori T. Laparoscopic and endoscopic cooperative surgery for gastric tumors: Perspective for actual practice and oncological benefits. World J Gastrointest Oncol 2018; 10:381-397. [PMID: 30487950 PMCID: PMC6247108 DOI: 10.4251/wjgo.v10.i11.381] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 09/15/2018] [Accepted: 10/11/2018] [Indexed: 02/05/2023] Open
Abstract
Laparoscopic and endoscopic cooperative surgery (LECS) is a surgical technique that combines laparoscopic partial gastrectomy and endoscopic submucosal dissection. LECS requires close collaboration between skilled laparoscopic surgeons and experienced endoscopists. For successful LECS, experience alone is not sufficient. Instead, familiarity with the characteristics of both laparoscopic surgery and endoscopic intervention is necessary to overcome various technical problems. LECS was developed mainly as a treatment for gastric submucosal tumors without epithelial lesions, including gastrointestinal stromal tumors (GISTs). Local gastric wall dissection without lymphadenectomy is adequate for the treatment of gastric GISTs. Compared with conventional simple wedge resection with a linear stapler, LECS can provide both optimal surgical margins and oncological benefit that result in functional preservation of the residual stomach. As technical characteristics, however, classic LECS involves intentional opening of the gastric wall, resulting in a risk of tumor dissemination with contamination by gastric juice. Therefore, several modified LECS techniques have been developed to avoid even subtle tumor exposure. Furthermore, LECS for early gastric cancer has been attempted according to the concept of sentinel lymph node dissection. LECS is a prospective treatment for GISTs and might become a future therapeutic option even for early gastric cancer. Interventional endoscopists and laparoscopic surgeons collaboratively explore curative resection. Simultaneous intraluminal approach with endoscopy allows surgeons to optimizes the resection area. LECS, not simple wedge resection, achieves minimally invasive treatment and allows for oncologically precise resection. We herein present detailed tips and pitfalls of LECS and discuss various technical considerations.
Collapse
Affiliation(s)
- Yuki Aisu
- Department of Digestive Surgery, Tenri Hospital, Tenri 632-8552, Nara, Japan
| | - Daiki Yasukawa
- Department of Surgery, Shiga University of Medical Science, Otsu 520-2192, Japan
| | - Yusuke Kimura
- Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Tomohide Hori
- Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan
| |
Collapse
|
|
28
|
Cives M, Strosberg JR. Gastroenteropancreatic Neuroendocrine Tumors. CA Cancer J Clin 2018; 68:471-487. [PMID: 30295930 DOI: 10.3322/caac.21493] [Citation(s) in RCA: 398] [Impact Index Per Article: 56.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 08/07/2018] [Accepted: 08/13/2018] [Indexed: 12/13/2022] Open
Abstract
Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from the diffuse neuroendocrine system. They frequently originate in the gastroenteropancreatic (GEP) tract and the bronchopulmonary tree, and their incidence has steadily increased in the last 3 decades. Fundamental biologic and genomic differences underlie the clinical heterogeneity of NETs, and distinct molecular features characterize NETs of different grades and different primary sites. Although surgery remains the cornerstone of treatment for localized tumors, systemic treatment options for patients with metastatic NETs have expanded considerably. Somatostatin analogs have demonstrated both antisecretory and antitumor efficacy. Peptide receptor radionuclide therapy with lutetium-177 dotatate (177 Lu-DOTATATE) has been approved for advanced GEP-NETs. The antitumor activity of everolimus has been demonstrated across a wide spectrum of NETs, and the antiangiogenic agent sunitinib has been approved for pancreatic NETs (pNETs). Chemotherapy with temozolomide and capecitabine has recently demonstrated an unprecedented prolongation of progression-free survival in a randomized trial of pNETs. Multiple retrospective series have reported the efficacy of liver-directed therapies both for palliating symptoms of hormone excess and for controlling tumor growth. Telotristat, an oral inhibitor of tryptophan hydroxylase, has been shown to reduce diarrhea in patients with carcinoid syndrome. Defining the therapeutic algorithm and identifying biomarkers predictive of response to treatments are among the main priorities for the next decade of research in the NET field.
Collapse
Affiliation(s)
- Mauro Cives
- Associate Professor, Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy
| | - Jonathan R Strosberg
- Associate Professor, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida
| |
Collapse
|
|
29
|
Grozinsky-Glasberg S, Alexandraki KI, Angelousi A, Chatzellis E, Sougioultzis S, Kaltsas G. Gastric Carcinoids. Endocrinol Metab Clin North Am 2018; 47:645-660. [PMID: 30098721 DOI: 10.1016/j.ecl.2018.04.013] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastric carcinoids, formally named gastric neuroendocrine neoplasms (NENs), are derived from enterochromaffin-like cells of the stomach and are increasingly diagnosed. A majority are designated as type I (related to autoimmune gastritis) and type II (related to gastrinoma) neoplasms that develop secondary to gastrin hypersecretion. Types I and II gastric carcinoids are mostly small-sized (1-2 cm), multiple, low-malignancy potential lesions mainly confined to the gastric mucosa/submucosa. These lesions have an indolent course and low metastatic potential. In contrast, type III gastric carcinoids are single, larger-sized (>2 cm), non-gastrin-related lesions that infiltrate the muscular layers associated with local and distant metastases.
Collapse
Affiliation(s)
- Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, P.O.B. 12000, Jerusalem 91120, Israel
| | - Krystallenia I Alexandraki
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Anna Angelousi
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Eleftherios Chatzellis
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Stavros Sougioultzis
- Department of Pathophysiology, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Gregory Kaltsas
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece.
| |
Collapse
|
|
30
|
Hirose Y, Sakata J, Endo K, Takahashi M, Saito R, Imano H, Kido T, Yoshino K, Sasaki T, Wakai T. A 0.8-cm clear cell neuroendocrine tumor G1 of the gallbladder with lymph node metastasis: a case report. World J Surg Oncol 2018; 16:150. [PMID: 30037336 PMCID: PMC6057040 DOI: 10.1186/s12957-018-1454-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2018] [Accepted: 07/19/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Neuroendocrine tumors (NETs) of the gallbladder are rare and generally considered low-grade malignancies. We herein describe a case of a patient with a 0.8-cm clear cell NET G1 of the gallbladder with nodal involvement. CASE PRESENTATION A 65-year-old man with no medical history indicative of von Hippel-Lindau (VHL) disease underwent laparoscopic cholecystectomy for cholecystolithiasis. There was a 0.8-cm tumor in the neck of the gallbladder. Histologic examination revealed nests or trabecular growth of clear cells with small round-to-oval nuclei. Immunohistochemically, tumor cells showed positivity for chromogranin A and synaptophysin; Ki-67 index was < 1.0%. Based on the World Health Organization 2010 classification, we made a diagnosis of clear cell variant of NET G1 without VHL disease. The tumor invaded the muscular layer and had no extension to the perimuscular connective tissue but had metastasized to a cystic duct node. A radical second resection with regional lymphadenectomy of the gallbladder was performed, and there was no metastasis on histology. After the definitive surgery, he was followed up for 10 months without adjuvant therapy and is alive and well with no evidence of recurrence. CONCLUSIONS Our experience suggests that, even when smaller than 1 cm, NET G1 of the gallbladder can metastasize. When NET G1 is incidentally identified in the gallbladder of a surgical specimen, detailed pathologic examination of the cystic duct node, when found, should be performed to guide whether a radical second resection with regional lymphadenectomy is appropriate.
Collapse
Affiliation(s)
- Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510 Japan
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510 Japan
| | - Kazuhiko Endo
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Masato Takahashi
- Department of Diagnostic Pathology, Akita Kousei Medical Center, Akita, Japan
| | - Reijiro Saito
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Hiroshi Imano
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Tomoki Kido
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Kei Yoshino
- Department of Digestive Surgery, Akita Kousei Medical Center, Akita, Japan
| | - Toshiki Sasaki
- Department of Diagnostic Pathology, Akita Kousei Medical Center, Akita, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 951-8510 Japan
| |
Collapse
|
|
31
|
Merath K, Bagante F, Beal EW, Lopez-Aguiar AG, Poultsides G, Makris E, Rocha F, Kanji Z, Weber S, Fisher A, Fields R, Krasnick BA, Idrees K, Smith PM, Cho C, Beems M, Schmidt CR, Dillhoff M, Maithel SK, Pawlik TM. Nomogram predicting the risk of recurrence after curative-intent resection of primary non-metastatic gastrointestinal neuroendocrine tumors: An analysis of the U.S. Neuroendocrine Tumor Study Group. J Surg Oncol 2018; 117:868-878. [PMID: 29448303 PMCID: PMC5992105 DOI: 10.1002/jso.24985] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 01/01/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND The risk of recurrence after resection of non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative-intent resection. METHODS A training set to develop the nomogram and test set for validation were identified. The predictive ability of the nomogram was assessed using c-indices. RESULTS Among 1477 patients, 673 (46%) were included in the training set and 804 (54%) in y the test set. On multivariable analysis, Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki-67 index (HR 1.08, 95% CI, 1.05-1.10; P < 0.001). GEP-NET invading adjacent organs had a HR of 1.65 (95% CI, 1.03-2.65; P = 0.038), similar to tumors ≥3 cm (HR 1.67, 95% CI, 1.11-2.51; P = 0.014). Patients with 1-3 positive nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12-2.87; P = 0.014) and 2.51 (95% CI, 1.50-4.24; P < 0.001), respectively. The nomogram demonstrated good ability to predict risk of recurrence (c-index: training set, 0.739; test set, 0.718). CONCLUSION The nomogram was able to predict the risk of recurrence and can be easily applied in the clinical setting.
Collapse
Affiliation(s)
- Katiuscha Merath
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Fabio Bagante
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
- Department of Surgery, University of Verona, Verona, Italy
| | - Eliza W Beal
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Alexandra G Lopez-Aguiar
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | | | | | - Flavio Rocha
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Zaheer Kanji
- Department of Surgery, Virginia Mason Medical Center, Seattle, Washington
| | - Sharon Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Alexander Fisher
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Ryan Fields
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Bradley A Krasnick
- Department of Surgery, Washington University School of Medicine, St. Louis, Wisconsin
| | - Kamran Idrees
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - Paula M Smith
- Division of Surgical Oncology, Department of Surgery, Vanderbilt University, Nashville, Tennessee
| | - Cliff Cho
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Wisconsin
| | - Megan Beems
- Division of Hepatopancreatobiliary and Advanced Gastrointestinal Surgery, Department of Surgery, University of Michigan, Ann Arbor, Wisconsin
| | - Carl R Schmidt
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Mary Dillhoff
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - Timothy M Pawlik
- Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| |
Collapse
|
|
32
|
Vanoli A, La Rosa S, Miceli E, Klersy C, Maragliano R, Capuano F, Persichella A, Martino M, Inzani F, Luinetti O, Di Sabatino A, Sessa F, Paulli M, Corazza GR, Rindi G, Bordi C, Capella C, Solcia E. Prognostic Evaluations Tailored to Specific Gastric Neuroendocrine Neoplasms: Analysis Of 200 Cases with Extended Follow-Up. Neuroendocrinology 2018; 107:114-126. [PMID: 29895024 DOI: 10.1159/000489902] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Accepted: 05/02/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Gastric neuroendocrine neoplasms (NENs) are very heterogeneous, ranging from mostly indolent, atrophic gastritis-associated, type I neuroendocrine tumors (NETs), through highly malignant, poorly differentiated neuroendocrine carcinomas (pdNECs), to sporadic type III NETs with intermediate prognosis, and various rare tumor types. Histologic differentiation, proliferative grade, size, level of gastric wall invasion, and local or distant metastases are used as prognostic markers. However, their value remains to be tailored to specific gastric NENs. METHODS Series of type I NETs (n = 123 cases), type III NETs (n = 34 cases), and pdNECs (n = 43 cases) were retrospectively collected from four pathology centers specializing in endocrine pathology. All cases were characterized clinically and histopathologically. During follow-up (median 93 months) data were recorded to assess disease-specific patient survival. RESULTS Type I NETs, type III NETs, and pdNECs differed markedly in terms of tumor size, grade, invasive and metastatic power, as well as patient outcome. Size was used to stratify type I NETs into subgroups with significantly different invasive and metastatic behavior. All 70 type I NETs < 0.5 cm (micro-NETs) were uneventful. Ki67-based grading proved efficient for the prognostic stratification of type III NETs; however, grade 2 (G2) was not associated with tumor behavior in type I NETs. Although G3 NETs (2 type I and 9 type III) had a very poor prognosis, it was found that patient survival was longer with type III G3 NETs compared to pdNECs. CONCLUSIONS Given the marked, tumor type-related behavior differences, evaluation of gastric NEN prognostic parameters should be tailored to the type of neoplastic disease.
Collapse
Affiliation(s)
- Alessandro Vanoli
- Department of Molecular Medicine, University of Pavia and Pathology Unit, IRCCS San Matteo Hospital, Pavia, Italy
| | - Stefano La Rosa
- Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland
| | - Emanuela Miceli
- Department of Internal Medicine, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy
| | - Catherine Klersy
- Clinical Epidemiology and Biometry Service, IRCCS San Matteo Hospital, Pavia, Italy
| | - Roberta Maragliano
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Francesca Capuano
- Department of Molecular Medicine, University of Pavia and Pathology Unit, IRCCS San Matteo Hospital, Pavia, Italy
| | - Andrea Persichella
- Department of Molecular Medicine, University of Pavia and Pathology Unit, IRCCS San Matteo Hospital, Pavia, Italy
| | - Michele Martino
- Department of Internal Medicine, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy
| | - Frediano Inzani
- Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore-Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Rome, Italy
| | - Ombretta Luinetti
- Department of Molecular Medicine, University of Pavia and Pathology Unit, IRCCS San Matteo Hospital, Pavia, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy
| | - Fausto Sessa
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Marco Paulli
- Department of Molecular Medicine, University of Pavia and Pathology Unit, IRCCS San Matteo Hospital, Pavia, Italy
| | - Gino Roberto Corazza
- Department of Internal Medicine, IRCCS San Matteo Hospital, University of Pavia, Pavia, Italy
| | - Guido Rindi
- Institute of Anatomic Pathology, Università Cattolica del Sacro Cuore-Fondazione Policlinico Universitario Agostino Gemelli, Rome, Italy
- European Neuroendocrine Tumor Society (ENETS) Center of Excellence, Rome, Italy
| | - Cesare Bordi
- Anatomic Pathology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Carlo Capella
- Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Enrico Solcia
- Department of Molecular Medicine, University of Pavia and Pathology Unit, IRCCS San Matteo Hospital, Pavia, Italy
| |
Collapse
|
|
33
|
Yazici C, Boulay BR. Evolving role of the endoscopist in management of gastrointestinal neuroendocrine tumors. World J Gastroenterol 2017; 23:4847-4855. [PMID: 28785139 PMCID: PMC5526755 DOI: 10.3748/wjg.v23.i27.4847] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 05/05/2017] [Accepted: 06/12/2017] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) are uncommon gastrointestinal neoplasms but have been increasingly recognized over the past few decades. Luminal NETs originate from the submucosa of the gastrointestinal tract and careful endoscopic exam is a key for accurate diagnosis. Despite their reputation as indolent tumors with a good prognosis, some NETs may have aggressive features with associated poor long-term survival. Management of NETs requires full understanding of tumor size, depth of invasion, local lymphadenopathy status, and location within the gastrointestinal tract. Staging with endoscopic ultrasound or cross-sectional imaging is important for determining whether endoscopic treatment is feasible. In general, small superficial NETs can be managed by endoscopic mucosal resection and endoscopic submucosal dissection (ESD). In contrast, NETs larger than 2 cm are almost universally treated with surgical resection with lymphadenectomy. For those tumors between 11-20 mm in size, careful evaluation can identify which NETs may be managed with endoscopic resection. The increasing adoption of ESD may improve the results of endoscopic resection for luminal NETs. However, enthusiasm for endoscopic resection must be tempered with respect for the more definitive curative results afforded by surgical treatment with more advanced lesions.
Collapse
|
|
34
|
Beduya D, Parasher G. Evaluation and Management of Mucosal and Submucosal Lesions in the Foregut. UPPER ENDOSCOPY FOR GI FELLOWS 2017:139-150. [DOI: 10.1007/978-3-319-49041-0_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
|
35
|
Sagatun L, Fossmark R, Jianu CS, Qvigstad G, Nordrum IS, Mjønes P, Waldum HL. Follow-up of patients with ECL cell-derived tumours. Scand J Gastroenterol 2016; 51:1398-405. [PMID: 27309188 DOI: 10.3109/00365521.2016.1169588] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To review the presentation, treatment and outcome of patients with type 1 gastric carcinoid tumours. MATERIAL AND METHODS We retrospectively reviewed medical records and re-evaluated histopathological specimens of 26 patients with type 1 gastric carcinoids treated at a single tertiary referral centre from 1993 to 2013, with median time of follow-up 52.5 months (IQR 90.8). RESULTS Seven patients (27%) had single tumours and 19 patients (73%) multiple tumours at the time of diagnosis. The median number of tumours and median diameter of largest tumour were 2.5 (IQR 3.2) and 6.0 mm (IQR 9.5) respectively. Median serum gastrin was 321.0 pmol/l (IQR 604.0) and median serum chromogranin A 7.7 nmol/l (IQR 5.3). Three patients had metastatic disease at the time of diagnosis and two developed metastases during follow-up. Patients with metastatic disease had larger primary tumours than the others (20.0 mm (IQR 28.5) vs. 5.0 mm (IQR 5.5), p = 0.04). There was a positive correlation between age and tumour size (r = 0.44, p = 0.03) and between serum chromogranin A and serum gastrin at diagnosis (r = 0.76, p = 0.001). Patients were either treated with surgery (n = 8 (31%)), a long-acting somatostatin analogue and/or gastrin receptor antagonist (n = 10 (39%)) for a period of time, or were observed without treatment (n = 8 (31%) with close endoscopic follow up. CONCLUSIONS Although gastric carcinoids have an overall good prognosis, a significant proportion develops metastatic disease. As partial and total gastrectomy is associated with major side effects, treatment with long-acting a somatostatin analogue or gastrin antagonist should be considered.
Collapse
Affiliation(s)
- Liv Sagatun
- a Department of Gastroenterology and Hepatology , St Olav's Hospital , Trondheim , Norway ;,b Department of Cancer Research and Molecular Medicine, Faculty of Medicine , Norwegian University of Science and Technology , Trondheim , Norway
| | - Reidar Fossmark
- a Department of Gastroenterology and Hepatology , St Olav's Hospital , Trondheim , Norway ;,b Department of Cancer Research and Molecular Medicine, Faculty of Medicine , Norwegian University of Science and Technology , Trondheim , Norway
| | - Constantin S Jianu
- a Department of Gastroenterology and Hepatology , St Olav's Hospital , Trondheim , Norway
| | - Gunnar Qvigstad
- a Department of Gastroenterology and Hepatology , St Olav's Hospital , Trondheim , Norway ;,b Department of Cancer Research and Molecular Medicine, Faculty of Medicine , Norwegian University of Science and Technology , Trondheim , Norway
| | - Ivar S Nordrum
- c Department of Pathology and Medical Genetics , St Olav's Hospital , Trondheim , Norway ;,d Department of Laboratory Medicine, Children and Woman Health , NTNU , Trondheim , Norway
| | - Patricia Mjønes
- b Department of Cancer Research and Molecular Medicine, Faculty of Medicine , Norwegian University of Science and Technology , Trondheim , Norway ;,c Department of Pathology and Medical Genetics , St Olav's Hospital , Trondheim , Norway
| | - Helge L Waldum
- a Department of Gastroenterology and Hepatology , St Olav's Hospital , Trondheim , Norway ;,b Department of Cancer Research and Molecular Medicine, Faculty of Medicine , Norwegian University of Science and Technology , Trondheim , Norway
| |
Collapse
|
|
36
|
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: 20] [Impact Index Per Article: 2.2] [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.
Collapse
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.
| |
Collapse
|
|
37
|
|
|
38
|
Jenny HE, Ogando PA, Fujitani K, Warner RRP, Divino CM. Laparoscopic antrectomy: a safe and definitive treatment in managing type 1 gastric carcinoids. Am J Surg 2016; 211:778-82. [PMID: 26992358 DOI: 10.1016/j.amjsurg.2015.08.040] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Revised: 08/15/2015] [Accepted: 08/18/2015] [Indexed: 01/02/2023]
Abstract
BACKGROUND Treatment for type 1 gastric carcinoid (T1GC) includes esophagogastroduodenoscopy (EGD), polypectomy, and antrectomy, but few studies compare outcomes. This study assessed risk-benefit ratio to determine the most effective treatment for T1GC. METHODS A retrospective review of 52 T1GC patients (ages 30 to 88 years; 77% female) presenting to Mount Sinai Medical Center between 2004 and 2012 was conducted. Patient demographics, procedures, and outcomes were reviewed, and patient satisfaction was assessed using a phone-administered validated questionnaire. Data were analyzed using SPSS version 20 software. RESULTS Average EGDs needed per follow-up year was significantly lower for antrectomy than polypectomy or EGD surveillance (.395 vs 1.038 vs 1.380, P = .002). Antrectomy patients exhibited decreased recurrence risk than polypectomy patients (11% vs 44%, P = .049), despite longer follow-up time (6.10 vs 4.39 years, P = .023). CONCLUSIONS Antrectomy treats T1GC with lower recurrence risk and less postintervention monitoring, whereas allowing patients to avoid the discomfort of repeated EGD surveillance and anxiety over a lingering condition.
Collapse
Affiliation(s)
- Hillary E Jenny
- Division of General Surgery, Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1259, New York, NY, 10029, USA
| | - Paul A Ogando
- Division of General Surgery, Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1259, New York, NY, 10029, USA
| | - Kenji Fujitani
- Division of General Surgery, Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1259, New York, NY, 10029, USA
| | - Richard R P Warner
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Carcinoid and Neuroendocrine Tumors, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Celia M Divino
- Division of General Surgery, Department of Surgery, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place Box 1259, New York, NY, 10029, USA; Center for Carcinoid and Neuroendocrine Tumors, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| |
Collapse
|
|
39
|
Lee JS, Kim GH, Park DY, Yoon JM, Kim TW, Seo JH, Lee BE, Song GA. Endoscopic Submucosal Dissection for Gastric Subepithelial Tumors: A Single-Center Experience. Gastroenterol Res Pract 2015; 2015:425469. [PMID: 26347772 PMCID: PMC4548140 DOI: 10.1155/2015/425469] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2015] [Revised: 07/09/2015] [Accepted: 07/13/2015] [Indexed: 12/11/2022] Open
Abstract
Background and Aims. Endoscopic submucosal dissection (ESD) has been accepted as a treatment modality for gastrointestinal epithelial tumors. Recently, ESD has been applied to resect subepithelial tumors (SETs) in the gastrointestinal tract, but clinical evidence on its efficacy and safety is limited. The aim of this study was to investigate the efficacy and safety of ESD for gastric SETs and to assess possible predictive factors for incomplete resection. Patients and Methods. Between January 2006 and December 2013, a total of 49 patients with gastric SET underwent ESD at our hospital. Clinicopathologic characteristics of patients and SETs, therapeutic outcomes, complications, and follow-up outcomes were evaluated. Results. The overall rates of en bloc resection and complete resection were 88% (43/49) and 84% (43/49), respectively. Complete resection rates in tumors originating from the submucosal layer were significantly higher than those in tumors originating from the muscularis propria layer (90% versus 56%, P = 0.028). In multivariate logistic regression analyses, tumor location (upper third: odds ratio [OR] 12.639, 95% confidence interval [CI] 1.087-146.996, P = 0.043) and layer of tumor origin (muscularis propria: OR 8.174, 95% CI 1.059-63.091, P = 0.044) were independently associated with incomplete resection. Procedure-related bleeding and perforation rates were both 4%. No recurrence was observed in patients with complete resection at a median follow-up period of 29 months (range: 7-83 months). Conclusions. ESD is an effective, safe, and feasible treatment for gastric SETs. The frequency of incomplete resection increases in tumors located in the upper third of the stomach and in those originating from the muscularis propria layer.
Collapse
Affiliation(s)
- Jin Sung Lee
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 602-739, Republic of Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 602-739, Republic of Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea
| | - Do Youn Park
- Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea
- Department of Pathology, Pusan National University School of Medicine, Busan 602-739, Republic of Korea
| | - Jong Min Yoon
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 602-739, Republic of Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea
| | - Tae Wook Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 602-739, Republic of Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea
| | - Jong Hun Seo
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 602-739, Republic of Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea
| | - Bong Eun Lee
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 602-739, Republic of Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea
| | - Geun Am Song
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 602-739, Republic of Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea
| |
Collapse
|
|
40
|
Eltrombopag Use in Thrombocytopenia for Endoscopic Submucosal Dissection of a Gastric Carcinoid. ACG Case Rep J 2015; 2:24-6. [PMID: 26157896 PMCID: PMC4435337 DOI: 10.14309/crj.2014.73] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 08/14/2014] [Indexed: 11/17/2022] Open
Abstract
Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain platelet levels for the safe and complete endoscopic submucosal dissection of a gastric carcinoid in a patient with severe thrombocytopenia due to cirrhosis and idiopathic thrombocytopenic purpura. We performed complete and safe endoscopic removal of a gastric carcinoid after correcting the thrombocytopenia.
Collapse
|
|
41
|
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: 31] [Impact Index Per Article: 3.1] [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.
Collapse
|
|
42
|
Management and disease outcome of type I gastric neuroendocrine tumors: the Mount Sinai experience. Dig Dis Sci 2015; 60:996-1003. [PMID: 25399327 DOI: 10.1007/s10620-014-3410-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 10/17/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM The incidence of gastric neuroendocrine tumors (NETs) has increased tenfold since the 1970s. Our aim was to describe the clinicopathologic profile, management, and outcomes of type I gastric NETs at The Mount Sinai Hospital. METHODS From existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation, we identified 56 patients with type I gastric NETs seen at The Mount Sinai Hospital from 1993 to 2012. We generated a comprehensive dataset encompassing demographic, clinical, endoscopic, and pathologic factors. Survival information was determined from medical records and the Social Security Death Index. Tumor-node-metastasis staging was conducted, and tumors were graded based on mitotic counts and Ki67 index. RESULTS Median NET size was 3.0 mm; 55.8 % displayed multifocal disease. Stages I, II, III, and IV disease were observed in 83.8, 10.8, 5.4, and 0 %, respectively. Tumors were either low (69.7 %) or intermediate (30.3 %) grade. Furthermore, 3.6 % of patients developed gastric dysplasia, and 5.5 % had gastric adenocarcinoma. Patients underwent endoscopy every 15 months, while 28.6 % underwent polypectomy, 32.7 % somatostatin therapy, and 46.4 % surgical resection. 5- and 10-year disease-specific survival was 100 %. CONCLUSIONS Most patients received annual endoscopic surveillance, with a minority undergoing surgical resection, though outcomes remained excellent independent of therapeutic approach. We identified a very low but real rate of loco-regional spread, despite the generally indolent behavior of type I gastric NETs. Several patients demonstrated concurrent dysplasia or adenocarcinoma, underscoring the efficacy of regular endoscopic management not only for gastric NETs, but also for dysplasia and adenocarcinoma.
Collapse
|
|
43
|
Fernandes D, Soares JB, Rolanda C. Gastric Mixed Adenoneuroendocrine Carcinoma. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2015; 22:34-36. [PMID: 28868368 PMCID: PMC5580157 DOI: 10.1016/j.jpge.2014.07.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 07/29/2014] [Indexed: 12/25/2022]
Affiliation(s)
- Dália Fernandes
- Department of Gastroenterology, Hospital Cova da Beira, Covilhã, Portugal.,Department of Gastroenterology, Hospital de Braga, Braga, Portugal
| | | | - Carla Rolanda
- Department of Gastroenterology, Hospital de Braga, Braga, Portugal.,Life and Health Sciences Research Institute, University of Minho, Braga, Portugal
| |
Collapse
|
|
44
|
Wang Y, Zhuo C, Shi D, Zheng H, Xu Y, Gu W, Cai S, Cai G. Unfavorable effect of small tumor size on cause-specific survival in stage IIA colon cancer, a SEER-based study. Int J Colorectal Dis 2015; 30:131-7. [PMID: 25392257 DOI: 10.1007/s00384-014-2056-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/25/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND We sought to determine the prognostic role of tumor size on cause-specific survival (CSS) of patients with stage IIA colon cancer. METHODS Surveillance, Epidemiology and End Results (SEER) database was utilized to identify patients with stage IIA colorectal cancer (examined lymph nodes ≥12) diagnosed from 1988 to 2003. The prognostic effect of tumor size on CSS was evaluated by univariate and multivariate analyses. RESULTS A total of 8775 patients were enrolled in the analysis. The median follow-up time was 109 months. As determined by minimal P value method, tumor sizes of 2.5 and 6.0 cm were used as optimal cutoff value to divide the cohort. The 8-year CSS of colon cancer with tumor sizes ≤2.5, 2.6-6.0, and >6.0 cm was 81.6, 86.2, and 86.7% respectively (P = 0.003). In the multivariate analysis of colon cancer, using ≤2.5-cm tumors as reference, decreased hazard ratio (HR) of CSS was observed in 2.6-6.0 cm (HR, 0.736; 95% confidence interval (CI), 0.599-0.905; P = 0.004) and >6.0 cm (HR, 0.770; 95% CI, 0.619-0.958; P = 0.019) tumors. CONCLUSIONS In stage IIA colon cancer, small tumor size represented a subset with decreased CSS. Further studies are merited to validate the unfavorable prognostic role of small tumor size in stage IIA colon cancer.
Collapse
Affiliation(s)
- Yuwei Wang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China
| | | | | | | | | | | | | | | |
Collapse
|
|
45
|
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: 10] [Impact Index Per Article: 0.9] [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.
Collapse
Affiliation(s)
- Yuichi Sato
- Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, 951-8121, Japan,
| |
Collapse
|
|
46
|
Yang Y, Li LQ, Zheng JT, Chen Q, Wang M. Diagnosis, treatment and prognosis of gastric neuroendocrine carcinoma. Shijie Huaren Xiaohua Zazhi 2014; 22:3831-3834. [DOI: 10.11569/wcjd.v22.i25.3831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the therapeutic effects, treatment strategies, clinicopathologic features, and prognosis of gastric-neuroendocrine carcinoma (G-NEC).
METHODS: According to the 2010 World Health Organization (WHO) classification of NEC, clinical data for 44 patients with G-NEC were analyzed retrospectively, including treatment methods, pathological features and prognosis.
RESULTS: All the 44 patients were followed. The median survival of these patients was 23.5 mo, and the overall 1-, 3- and 5-year survival rates were 70.8%, 25.3% and 12.0%, respectively. Univariate analysis showed that age, gender, tumor size, and tumor location were not correlated with prognosis, but surgical procedure, invasive depth, lymph node and distant metastases were significantly correlated with prognosis.
CONCLUSION: G-NEC has a high recurrence rate and poor prognosis. The prognosis depends on multiple factors such as carcinoma infiltration and metastasis and surgical treatment. Multidisciplinary treatment should be given in these cases.
Collapse
|
|
47
|
Kaltsas G, Grozinsky-Glasberg S, Alexandraki KI, Thomas D, Tsolakis AV, Gross D, Grossman AB. Current concepts in the diagnosis and management of type 1 gastric neuroendocrine neoplasms. Clin Endocrinol (Oxf) 2014; 81:157-168. [PMID: 24750249 DOI: 10.1111/cen.12476] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Revised: 04/07/2014] [Accepted: 04/15/2014] [Indexed: 12/13/2022]
Abstract
The vast majority of gastrin-related gastrointestinal neuroendocrine neoplasms (GI-NENs) develop in the context of chronic atrophic gastritis (type 1), a condition closely related to autoimmune thyroid diseases. These neoplasms are defined as gastric NENs type 1 (GNEN1) and have recently been shown to constitute the commonest GI-NENs in a prospective study. GNEN1s are usually multiple and follow a relative indolent course, raising questions regarding the extent that such patients should be investigated and the appropriate therapeutic interventions needed. Recently, a number of consensus statements and guidelines have been published from various societies dealing with the diagnosis and management of GI-NENs. Endocrinologists are among the many different medical specialties involved in GNEN1s diagnosis and management. However, despite recent advances, few randomized trials are available, and thus existing evidence remains relatively weak compared to other malignancies. The purpose of this review is to provide recent evidence along with currently employed modalities addressing the diagnosis, management, long-term follow-up and potential comorbidities of GNEN1s.
Collapse
Affiliation(s)
- Gregory Kaltsas
- Department of Pathophysiology, National University of Athens, Athens, Greece
| | | | | | | | | | | | | |
Collapse
|
|
48
|
Kim HH, Kim GH, Kim JH, Choi MG, Song GA, Kim SE. The efficacy of endoscopic submucosal dissection of type I gastric carcinoid tumors compared with conventional endoscopic mucosal resection. Gastroenterol Res Pract 2014; 2014:253860. [PMID: 24693280 PMCID: PMC3947882 DOI: 10.1155/2014/253860] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 01/09/2014] [Indexed: 12/13/2022] Open
Abstract
Background and Aims. Conventional endoscopic submucosal resection (EMR) of carcinoid tumors often involves the resection margin, which necessitates further intervention. Endoscopic submucosal dissection (ESD) is widely accepted for removing carcinoid tumors. We aimed to evaluate the clinical usefulness of ESD with that of EMR for resection of type I gastric carcinoid tumors. Patients and Methods. The study enrolled 62 patients (37 males, 25 females; median age, 50 years; range, 40-68 years) who were treated with EMR or ESD at three hospitals; the study group had 87 type I gastric carcinoid tumors with an estimated size of ≤10 mm. The complete resection rate and the complications associated with these two procedures were analyzed. Results. The overall ESD complete resection rate was higher than that of the EMR rate (94.9% versus 83.3%, P value = 0.174). A statistically lower vertical margin involvement rate was achieved when ESD was performed compared to when EMR was performed (2.6% versus 16.7%, P value = 0.038). The complication rate was not significantly different between the two groups. Conclusions. ESD showed a higher complete resection rate, particularly for the vertical margin, with a similar complication rate. We mildly recommend ESD rather than EMR for removing type I gastric carcinoid tumors.
Collapse
Affiliation(s)
- Hyung Hun Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul 137-701, Republic of Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University, School of Medicine, Busan 614-735, Republic of Korea
| | - Ji Hyun Kim
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, Gaegeum-dong, Busanjin-Gu, Busan 602-739, Republic of Korea
| | - Myung-Gyu Choi
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul 137-701, Republic of Korea
| | - Geun Am Song
- Department of Internal Medicine, Pusan National University, School of Medicine, Busan 614-735, Republic of Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan 602-702, Republic of Korea
| |
Collapse
|
|
49
|
Grozinsky-Glasberg S, Thomas D, Strosberg JR, Pape UF, Felder S, Tsolakis AV, Alexandraki KI, Fraenkel M, Saiegh L, Reissman P, Kaltsas G, Gross DJ. Metastatic type 1 gastric carcinoid: a real threat or just a myth? World J Gastroenterol 2013; 19:8687-8695. [PMID: 24379587 PMCID: PMC3870515 DOI: 10.3748/wjg.v19.i46.8687] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Revised: 08/25/2013] [Accepted: 09/03/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1 (GCA1). METHODS Information on clinical, biochemical, radiological, histopathological findings, the extent of the disease, as well as the use of different therapeutic modalities and the long-term outcome were recorded. Patients' data were assessed at presentation, and thereafter at 6 to 12 monthly intervals both clinically and biochemically, but also endoscopically and histopathologically. Patients were evaluated for the presence of specific symptoms; the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also recorded. The evaluation of response to treatment was defined using established WHO criteria. RESULTS We studied twenty consecutive patients with a mean age of 55.1 years. The mean follow-up period was 83 mo. Twelve patients had regional lymph node metastases and 8 patients had liver metastases. The primary tumor mean diameter was 20.13 ± 10.83 mm (mean ± SD). The mean Ki-67 index was 6.8% ± 11.2%. All but one patient underwent endoscopic or surgical excision of the tumor. The disease was stable in all but 3 patients who had progressive liver disease. All patients remained alive during the follow-up period. CONCLUSION Metastatic GCA1 carries a good overall prognosis, being related to a tumor size of ≥ 1 cm, an elevated Ki-67 index and high serum gastrin levels.
Collapse
|
|
50
|
Kwon YH, Jeon SW, Kim GH, Kim JI, Chung IK, Jee SR, Kim HU, Seo GS, Baik GH, Choi KD, Moon JS. Long-term follow up of endoscopic resection for type 3 gastric NET. World J Gastroenterol 2013; 19:8703-8708. [PMID: 24379589 PMCID: PMC3870517 DOI: 10.3748/wjg.v19.i46.8703] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2013] [Revised: 09/27/2013] [Accepted: 10/19/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To clarify the short and long-term results and to prove the usefulness of endoscopic resection in type 3 gastric neuroendocrine tumors (NETs). METHODS Of the 119 type 3 gastric NETs diagnosed from January 1996 to September 2011, 50 patients treated with endoscopic resection were enrolled in this study. For endoscopic resection, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) was used. Therapeutic efficacy, complications, and follow-up results were evaluated retrospectively. RESULTS EMR was performed in 41 cases and ESD in 9 cases. Pathologically complete resection was performed in 40 cases (80.0%) and incomplete resection specimens were observed in 10 cases (7 vs 3 patients in the EMR vs ESD group, P = 0.249). Upon analysis of the incomplete resection group, lateral or vertical margin invasion was found in six cases (14.6%) in the EMR group and in one case in the ESD group (11.1%). Lymphovascular invasions were observed in two cases (22.2%) in the ESD group and in one case (2.4%) in the EMR group (P = 0.080). During the follow-up period (43.73; 13-60 mo), there was no evidence of tumor recurrence in either the pathologically complete resection group or the incomplete resection group. No recurrence was reported during follow-up. In addition, no mortality was reported in either the complete resection group or the incomplete resection group for the duration of the follow-up period. CONCLUSION Less than 2 cm sized confined submucosal layer type 3 gastric NET with no evidence of lymphovascular invasion, endoscopic treatment could be considered at initial treatment.
Collapse
|