Figure - available via license: Creative Commons Attribution 3.0 Unported
Content may be subject to copyright.
Pathophysiologic mechanisms of normal acid secretion from parietal cells after a meal (a) and ECL-cell hyperplasia in patients with achlorhydria and loss of somatostatin negative feedback (b).
Source publication
Gastric carcinoid tumors (GCs) are rare lesions representing less than 10% of carcinoid tumors and less than 1% of all stomach neoplasms. There are three distinct types of gastric carcinoids; type I includes the vast majority (70-85%) of these neoplasms that are closely linked to chronic atrophic gastritis. Type II which accounts for 5-10 %, is ass...
Similar publications
Gastric neuroendocrine neoplasms of the stomach can be divided into the usually well-differentiated, hypergastrinemia-dependent type I and II lesions and the more aggressively behaving gastrin-independent type III lesions. Studying menin and its complex interrelationship with gastrin may provide insight into tumor biology at the clinical level and...
Citations
... Пациенты с АИГ с преобладаю щей атрофией тела желудка также подвержены повышенному риску возникновения нейроэндокринных опухолей (НЭО) GI-типа по классификации G-NET ВОЗ 2017 г. [51,52] Эти опухоли развиваются как следствие потери париетальных клеток, что приводит к снижению секреции желудочного сока, последующей стойкой гипергастринемии и гиперплазии энтерохромаффинноподобных клеток (ECL), а далее в небольшом проценте случаев к дисплазии ECL и НЭО желудка. На основании продольных когортных исследований частота НЭО желудка GI-типа у пациентов с хроническим АГ оценивается как 0,4-0,7% в год [53][54][55][56]. Хотя это редкая причина (<1%) неоплазии желудка, у 50% пациентов с карциноидными опухолями желудка имеется пернициозная анемия [57][58][59]. ...
Diagnosis of autoimmune gastritis (AIG) is often challenging because of the absence of typical symptoms. Clinical guidelines are lacking, which results in inadequate treatment and poor cancer screening. This work presents an overview of current management options and aims at raising awareness for this disease. The paper also describes a clinical case of the full-scale course of AIG with all its complications. Autoimmune gastritis is mostly considered as a disease of elderly with vitamin B12 deficiency and pernicious anaemia. Today it is recognized that AIG is found with a similar prevalence in all age groups, with iron deficiency being a frequent symptom. Conventional therapy consists of adequate iron and vitamin B12 supplementation, as well as symptomatic approaches. The associated risk for gastric adenocarcinoma and gastric neuroendocrine tumours requires regular endoscopic follow-up. New treatments aiming to reduce gastric atrophy and cancer risk are currently under development. Thus, treatment of autoimmune gastritis should focus on optimizing supplementation of vitamin and macronutrient deficiencies, symptomatic therapy that improves quality of life, and include cancer prevention measures. Clinical studies should address the possibility to arrest the inflammation process and to prevent progression of AIG. The author of the article suggests that itopride hydrochloride and rebamipide will be used for symptomatic and pathogenetic therapy. The problem facing gastroenterologists today is to develop domestic guidelines for the management and screening endoscopic intervals of patients with AIG.
... Type III tumors are single lesions, generally larger than 2 cm, located mainly in the gastric antrum and fundus. And type IV tumors generally manifest as multiple small lesions 5,20,31 . In this study, there was a predominance of cases with single lesions, larger than 1.5 cm, and located in the gastric antrum -a profile compatible with type III. ...
BACKGROUND
Gastric neuroendocrine tumors are a heterogeneous group of neoplasms that produce bioactive substances. Their treatment varies according to staging and classification, using endoscopic techniques, open surgery, chemotherapy, radiotherapy, and drugs analogous to somatostatin.
AIMS
To identify and review cases of gastric neuroendocrine neoplasia submitted to surgical treatment.
METHODS
Review of surgically treated patients from 1983 to 2018.
RESULTS
Fifteen patients were included, predominantly female (73.33%), with a mean age of 55.93 years. The most common symptom was epigastric pain (93.3%), and the mean time of symptom onset was 10.07 months. The preoperative upper digestive endoscopy (UDE) indicated a predominance of cases with 0 to 1 lesion (60%), sizing ≥1.5 cm (40%), located in the gastric antrum (53.33%), with ulceration (60%), and Borrmann III (33.33%) classification. The assessment of the surgical specimen indicated a predominance of invasive neuroendocrine tumors (60%), with angiolymphatic invasion in most cases (80%). Immunohistochemistry for chromogranin A was positive in 60% of cases and for synaptophysin in 66.7%, with a predominant Ki-67 index between 0 and 2%. Metastasis was observed in 20% of patients. The surgical procedure most performed was subtotal gastrectomy with Roux-en-Y reconstruction (53.3%). Tumor recurrence occurred in 20% of cases and a new treatment was required in 26.67%.
CONCLUSIONS
Gastric neuroendocrine tumors have a low incidence in the general population, and surgical treatment is indicated for advanced lesions. The study of its management gains importance in view of the specificities of each case and the need for adequate conduct to prevent recurrences and complications.
HEADINGS:
Stomach neoplasms; Neuroendocrine tumors; Surgical oncology
... Type 2 G-NETs are less common (5-8% of all G-NETs) and are similar to type 1 G-NETs with regards to cellular composition and the association with hypergastrinemia, though they more frequently metastasize and are associated with multiple endocrine neoplasia type 1 (MEN1) and Zollinger-Ellison syndrome. [34][35][36] Type 3 G-NETs are not associated with hypergastrinemia or MEN1. They account for 14-25% of all G-NETs and, importantly, have the greatest tendency to metastasize. ...
Practice of neuroendocrine neoplasms (NENs) of the digestive tract, which comprise a highly diverse group of tumors with a rising incidence, faces multiple biological, diagnostic, and therapeutic issues. Part of these issues are due to misuse and misinterpretation of the classification and terminology of NENs of the digestive tract, which make it increasingly challenging to evaluate and compare literature. For instance, grade 3 neuroendocrine tumors (NETs) are frequently referred to as neuroendocrine carcinomas (NECs) and vice versa, while NECs are by definition high grade and therefore constitute a separate entity from NETs. Moreover, the term NETs is regularly misused to describe NENs in general, and NETs are frequently referred to as benign, while they should always be considered malignancies as they do have metastatic potential. To prevent misconceptions in future NEN-related research, we reviewed the most recent terminology used to classify NENs of the digestive tract and created an overview that combines the classification of these NENs according to the World Health Organization (WHO) with location- and functionality-based classifications. This overview may help clinicians and researchers in understanding current literature and could serve as a guide in the clinic as well as for writing future studies on NENs of the digestive tract. In this way, we aim for the universal use of terminology, thereby providing an efficient foundation for future NEN-related research.
... However, their incidence has been increasing, probably due to the growing use of digestive endoscopies [3][4][5]. Type 1 gastric carcinoids (GC-1) are the most frequent subgroup; they are usually associated with chronic atrophic gastritis and hypergastrinemia [6]. Type 2 gastric carcinoid tumors are gastrin-producing tumors (Zolliger-Ellison syndrome) and usually occur in the context of multiple endocrine neoplasia type 1 (MEN-1). ...
... In addition, the implementation of screening in syndromes such as MEN-1 has facilitated the active search and diagnosis of gastro-entero-pancreatic neuroendocrine tumors in these patients [12]. For these reasons, it remains unclear whether this disease is really on the rise or whether it is a reporting artifact [4,13,14]. One of the causes cited for the increased incidence of GC-1 is the widespread use of proton pump inhibitors. ...
... Pathophysiologically, GC-1s are associated with autoimmune atrophic gastritis [3] with the complete atrophy of the oxyntic mucosa, which produces achlorhydria and intrinsic factor deficiency. When achlorhydria persists, the G cells in the gastric antrum experience hyperplasia, and excessive secretion of gastrin occurs [4]. Hypergastrinemia promotes enterochromaffin cell hyperplasia, which may lead to the appearance of GC-1s [14]; these are usually not very aggressive and small in size [8]. ...
Background:
Type 1 gastric neuroendocrine tumors (GC-1) represent an uncommon subtype of neoplasms. Endoscopic resection has been proposed as the treatment of choice; active surveillance may be performed in those smaller than 1 cm, while gastric surgery may be performed for those with frequent recurrences. The antiproliferative effect of somatostatin analogues (SSA) is well known, and their action on GC-1s has been postulated as a chronic treatment to reduce recurrence.
Methods:
A two-centered, retrospective, observational study that included nine patients (55.6% women) diagnosed with GC-1, receiving long-term treatment with SSA, with a median follow-up from baseline of 22 months, was undertaken. Endoscopic follow-up, extension study, and analytical values of chromogranin A (Cg A) and gastrin were collected.
Results:
In total, 88.9% of patients presented partial or complete response. Treatment with SSA was the only independent factor with a trend to prevent tumor recurrence (Odds Ratio 0.054; p = 0.005). A nonsignificant tendency toward a decrease in CgA and gastrin was observed; lack of significance was probably related to concomitant treatment with proton pump inhibitors in some patients.
Conclusions:
Chronic treatment with SSA is a feasible option for recurrent GC-1s that are difficult to manage using endoscopy or gastrectomy. Randomized clinical trials to provide more scientific evidence are still needed.
... Diagnosis and Treatment of Gastric Neuroendocrine Tumors3형은 어떤 알려진 임상적 조건과 관련 없이 산발적 (sporadic)으로 발생하고 공격적인 행동 양식을 보이며[10], 전체 위 신경내분비종양의 10-15% 정도를 차지하 는 것으로 보고되고 있다[24].1, 2형과 달리 위축성 위염 등의 다른 위 병변과의 관련성을 보이지 않으면서 남자에 게 더 흔하고, 종양 자체가 가스트린을 만드는 경우를 제 외하고 대개 혈중 가스트린과 위산의 생성은 정상 범주에 속한다[25]. 주로 2 cm보다 큰 단독의 궤양성, 또는 침윤 치를 올릴 수 있으므로 가급적 1주 이상 약제를 중단한 후 에 측정하도록 한다. ...
... [40] Regarding the therapeutic approach, annual or twice yearly endoscopic surveillance for small tumors (<10 mm diameter), surgical therapy (antrectomy, gastrectomy), endoscopic therapy (polypectomy, endoscopic mucosal resection or endoscopic submucosal dissection) for tumors >10 mm diameter, longacting somatostatin analogs lanreotide and octreotide, are available options for type 1 g-NETs. [41][42][43][44][45][46][47] A gastrin/cholecystokinin 2 receptor antagonist, Netazepide, showed promising results, by decreasing the number and the size of the tumors and by normalizing CgA levels. [48] Some authors advocate antrectomy in order to eliminate the gastrin stimulus that promotes tumor growth, and local resection of the largest tumors with subsequent endoscopic surveillance of the gastric remnant. ...
Rationale:
Gastric neuroendocrine neoplasms (g-NENs) represent a distinctive group of gastric tumors, stratified into different prognostic categories according to different histological characteristics, put forth in the 2018 World Health Organization classification system. The clinical presentations, as well as pathological features, represent important data in establishing the type of the tumor, in estimating the tumor behavior, and in selecting the best therapeutic strategy. In our case series we presented different clinical scenarios that may be encountered in practice regarding gastric NENs. We performed a literature review and discussed diagnostic strategy, current classification system, precursor lesions, and therapeutic options in g-NENs.
Patient concerns:
The first patient was a 41-year-old female with weight loss, persistent dyspeptic complaints and a history of pernicious anemia. In the second clinical case a 61-year-old man was admitted with heartburn, abdominal pain, diarrhea and mild iron deficiency anemia. The third patient was a 56-year-old male with a history of neoplasia, admitted for weight loss, dyspeptic complaints, and liver metastases.
Diagnosis:
All the 3 patients underwent upper endoscopy with targeted biopsies. Histopathological and laboratory evaluation, together with imagistic evaluation (abdominal ultrasound, endoscopic ultrasound, and magnetic resonance imaging) allowed the distinction between 3 different types of gastric tumors: type 1 enterochromaffin-like-cell G1 NET, type 2 enterochromaffin-like-cell G2 NET, and type 3 G2 NET with liver metastases.
Interventions:
Endoscopic polypectomy of the largest lesion was performed in patient with type 1 g-NET and autoimmune chronic atrophic gastritis, followed by regular endoscopic surveillance with biopsies. In type 2 g-NET associated with pancreatic gastrinoma, pancreaticoduodenectomy with total gastrectomy were performed. In type 3 g-NET, detected in metastatic stage, oncologic therapy was performed.
Outcomes:
The patients follow-up was selected according to tumor behavior, from regular endoscopic surveillance to oncology follow-up. The prognosis was good in case 1, whilst poorer outcomes were associated with more aggressive tumors in case 2 and case 3.
Lessons:
g-NENs are rare tumors with distinct clinical and histological features. Our case series emphasized the role of close collaboration between clinician and pathologist, as well as the importance of a detailed pathology report.
... Type 1 G1 gastric NETs usually have an excellent prognosis, dependent on the following conventional factors: tumour size, degree of deep mucosal invasion, and extent of vascular and lymphatic invasion [2]. Metastasis occurs in 2-5% of cases, but Grozinsky-Glasberg et al. showed, in a cohort of 20 metastatic type 1 NETs, that metastasis had no clear effect on prognosis [5,11,12]. Depending on the series considered, the proportion of G2 tumours ranges from 10 to 25% [10,13], and may be slightly higher than previously thought, but gastric G3 NETs remain exceptional. Most of the published cases were type 3 tumours [14][15][16][17]. ...
Gastric type 1 neuroendocrine tumours are considered to have low rates of proliferation and a good prognosis. We report here a patient with an aggressive well-differentiated high-grade gastric neuroendocrine tumour (gastric grade 3 NET), in a context of autoimmune gastritis. Consistent with grade 3 disease, the tumour had a Ki-67 proliferation index of 30%. Targeted next-generation sequencing identified variants of four genes, including a pathogenic ATM variant underlying the differentiation and metastatic potential of the tumour. Liver metastasis was diagnosed during follow-up, and the patient died after 6 years, due to disease progression.
... Gastric carcinoids are most commonly diagnosed on endoscopic ultrasound, which demonstrates lesions in the deep mucosa or submucosa. 63 The management of gastric carcinoids are dependent on the subtype and size of the tumor. 61 Type 3 gastric carcinoids are treated with subtotal or total gastrectomy. ...
This review article discusses the diagnoses and treatment of patients with multiple endocrine neoplasia type 1 (MEN 1). The most common tumors associated with MEN 1 are located in the pancreas, pituitary, and parathyroid glands. Less common tumors include neuroendocrine tumors of the lung and thymus, adrenal tumors, and cutaneous lesions. This article describes the diagnosis, clinical manifestations, treatment, and surveillance of tumors associated with patients who are diagnosed with MEN 1.
... 4 An extremely rare form of gNET (type IV) may also arise from the gastrin or serotonin producing endocrine cells of the stomach. 5 Patients with this pathology present with upper abdomen pain, bloating, nausea or vomiting, symptoms of anemia, weight loss, or hematemesis. Further evaluation may reveal an associated condition such as Zollinger-Ellison's syndrome or multiple endocrine neoplasia type 1. 4 Gastric polyps may incidentally be found on UGIE. ...
Gastric neuroendocrine tumor (gNET) is a rare carcinoid of the stomach whose incidence is increasing due to widespread use of upper gastrointestinal endoscopy (UGIE). There are four types of gNETs with different management strategies and prognosis. Here, we present a patient who came with abdomen pain and intermittent melena. UGIE showed a sessile polyp in the stomach. The patient subsequently underwent polypectomy and was symptomatically relieved.
... In their patient, the diagnosis of carcinoid tumor came 16 years after his diagnosis of AIH. Although our patient did not have features suspicious for carcinoid tumor, it potentially increases her risk of developing it in the future, as studies have shown an increased prevalence of carcinoid tumors in patients with PA [9,10]. It is vital that the clinician identifies this association as it can potentially allow patients with AIH and PA to get screened for gastric carcinoid tumors and have it treated at an earlier stage. ...
The co-occurrence of autoimmune hepatitis (AIH) and pernicious anemia (PA) is extremely rare. We present a case of a 70-year-old woman with AIH who presented for the evaluation of poor appetite and weight loss. Laboratory studies were significant for microcytic anemia, B12, and iron deficiency. Esophagogastroduodenoscopy showed diffuse gastric mucosal atrophy, and the pathology from the body of the stomach showed chronic gastritis. Additional testing was positive for parietal cell antibody and intrinsic factor blocking antibody, confirming the diagnosis of PA. To the best of our knowledge, there is only one documented case of AIH associated with PA.
