Diagnosis and Management of Gastric Neuroendocrine Neoplasms
Diagnosis and Management of Gastric Neuroendocrine Neoplasms
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.
Gastrointestinal neuroendocrine neoplasms (GI-NENs) arise from cells of the diffuse endocrine system. These tumours can synthesize, store and secrete amines and peptides that are used to identify them; in addition, when bioactive, these compounds can cause distinct clinical syndromes. GI-NENs may be diagnosed on the basis of the presence of symptoms attributable to clinical syndromes (functioning tumours), but the majority present with local symptoms and/or mass effects (nonfunctioning tumours). GI-NENs were originally considered to be rare, but recent data have suggested that they are increasingly being diagnosed with an estimated incidence of 2·5–5 cases/100 000/year. Although this might be attributed to the increased number of screening procedures employed, autopsy data have shown that GI-NENs are probably more common than previously believed.
The majority of GI-NENs are regarded as well-differentiated tumours that follow a prolonged course even in the presence of metastases. In contrast, poorly differentiated GI-NENs, constituting a minority of GI-NENs, follow an aggressive course similar to small- and large-cell lung carcinomas (SCLC/LCLC), albeit with a more prolonged survival. Since 2006 and after the implementation of specific classification systems, it has become apparent that primary site of tumour origin, degree of tumour cell proliferation based on Ki-67 labelling index (LI) defining tumour grade and extent of disease based on TNM staging identify different tumour subtypes and have an impact on prognosis (Table 1 and Table 2). Following the diagnosis of GI-NENs, a meticulous work-up employing biochemical, radiological, radionuclide and histological assessments is required to identify indices used to predict prognosis and select appropriate treatment(s). It is therefore vital for the clinicians to familiarize themselves with all recent developments involving diagnostic and therapeutic approaches to provide evidence-based and cost-effective patient care.
A recent prospective study has indicated that gastric NENs (GNENs) are the most common GI-NENs and constitute up to 23% of all GI-NENs recorded over a year. Gastric NENs are further subdivided into types 1–3 on the basis of their pathogenesis; types 1 and 2 are usually multiple and related to gastrin hypersecretion, in contrast to type 3, which is mostly single and not gastrin related (Table 3). Type 1 GNENs are the result of excessive gastrin secretion secondary to atrophic gastritis, whereas type 2 GNENs develop secondary to a gastrin-secreting tumour of either the duodenum or pancreas, often in the context of multiple endocrine neoplasia type 1 (MEN1). While GNEN type 3 is usually highly malignant resembling gastric carcinomas, the vast majority of GNENs are type 1 (GNEN1), which usually follow an indolent course, although a subset may become relatively aggressive. Selection of the most appropriate treatment modality and follow-up strategy of GNEN1 depends on the associated or underlying disease process, determined by endoscopic and histological techniques. It is therefore important to be able to identify GNEN1 at high risk for a more aggressive course and to utilize targeted diagnostic and therapeutic approaches in a cost-effective and efficient manner for the great majority, which have an indolent and essentially benign course.
Abstract and Introduction
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.
Introduction
Gastrointestinal neuroendocrine neoplasms (GI-NENs) arise from cells of the diffuse endocrine system. These tumours can synthesize, store and secrete amines and peptides that are used to identify them; in addition, when bioactive, these compounds can cause distinct clinical syndromes. GI-NENs may be diagnosed on the basis of the presence of symptoms attributable to clinical syndromes (functioning tumours), but the majority present with local symptoms and/or mass effects (nonfunctioning tumours). GI-NENs were originally considered to be rare, but recent data have suggested that they are increasingly being diagnosed with an estimated incidence of 2·5–5 cases/100 000/year. Although this might be attributed to the increased number of screening procedures employed, autopsy data have shown that GI-NENs are probably more common than previously believed.
The majority of GI-NENs are regarded as well-differentiated tumours that follow a prolonged course even in the presence of metastases. In contrast, poorly differentiated GI-NENs, constituting a minority of GI-NENs, follow an aggressive course similar to small- and large-cell lung carcinomas (SCLC/LCLC), albeit with a more prolonged survival. Since 2006 and after the implementation of specific classification systems, it has become apparent that primary site of tumour origin, degree of tumour cell proliferation based on Ki-67 labelling index (LI) defining tumour grade and extent of disease based on TNM staging identify different tumour subtypes and have an impact on prognosis (Table 1 and Table 2). Following the diagnosis of GI-NENs, a meticulous work-up employing biochemical, radiological, radionuclide and histological assessments is required to identify indices used to predict prognosis and select appropriate treatment(s). It is therefore vital for the clinicians to familiarize themselves with all recent developments involving diagnostic and therapeutic approaches to provide evidence-based and cost-effective patient care.
A recent prospective study has indicated that gastric NENs (GNENs) are the most common GI-NENs and constitute up to 23% of all GI-NENs recorded over a year. Gastric NENs are further subdivided into types 1–3 on the basis of their pathogenesis; types 1 and 2 are usually multiple and related to gastrin hypersecretion, in contrast to type 3, which is mostly single and not gastrin related (Table 3). Type 1 GNENs are the result of excessive gastrin secretion secondary to atrophic gastritis, whereas type 2 GNENs develop secondary to a gastrin-secreting tumour of either the duodenum or pancreas, often in the context of multiple endocrine neoplasia type 1 (MEN1). While GNEN type 3 is usually highly malignant resembling gastric carcinomas, the vast majority of GNENs are type 1 (GNEN1), which usually follow an indolent course, although a subset may become relatively aggressive. Selection of the most appropriate treatment modality and follow-up strategy of GNEN1 depends on the associated or underlying disease process, determined by endoscopic and histological techniques. It is therefore important to be able to identify GNEN1 at high risk for a more aggressive course and to utilize targeted diagnostic and therapeutic approaches in a cost-effective and efficient manner for the great majority, which have an indolent and essentially benign course.
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