Gastrointestinal Neuroendocrine Tumors: Clinical and Pathological Correlates

2019 ◽  
Vol 03 (01) ◽  
pp. 003-013
Author(s):  
Sanjit Datta ◽  
Annika Sinha ◽  
Baljendra Kapoor
Keyword(s):  
Neuroendocrine Tumors ◽  
Somatostatin Receptor ◽  
Management Strategies ◽  
Survival Rates ◽  
Endocrine System ◽  
Treatment Modalities ◽  
Clinical Syndromes ◽  
Wide Range ◽  
Poorly Differentiated ◽  
Diffuse Endocrine System

AbstractGastrointestinal neuroendocrine tumors (GI-NETs), previously classified as carcinoid tumors, are rare cancers that arise from cells of the diffuse endocrine system of the gastrointestinal tract. These tumors most commonly arise from the bronchus, jejunoileum, or colon/rectum. They produce peptide products that can lead to identifiable clinical syndromes such as carcinoid syndrome, which is classically associated with diarrhea, flushing, and heart disease. The latest classifications of GI-NETs include pancreatic NETs, which can produce a wide range of pancreatic hormones leading to syndromes such as Zollinger–Ellison's syndrome. The prognosis for patients with GI-NETs varies widely depending on the size, location, and presence of metastatic disease, with 5-year survival rates ranging from 0 to 15% for poorly differentiated NETs and 10-year survival rates of up to 100% for patients with insulinomas smaller than 2 cm. A wide range of treatment modalities is commonly used to treat GI-NETs, including surgical and endoscopic resection, locoregional therapies, cytotoxic chemotherapy, and somatostatin receptor targeted therapy. The goal of this review is to detail the classification, epidemiology, clinical syndromes, diagnosis, and staging of these tumors and to provide an overview of management strategies.

scholarly journals On the history and some characteristics of neuroendocrine tumors of the gastrointestinal tract. Review. Part 1

2021 ◽  
pp. 60-72
Author(s):  
S. Rybakov
Keyword(s):  
Gastrointestinal Tract ◽  
Neuroendocrine Tumors ◽  
Endocrine System ◽  
Secretory Activity ◽  
Clinical Syndrome ◽  
Biologically Active ◽  
Clinical Aspects ◽  
Clinical Syndromes ◽  
Diffuse Endocrine System ◽  
Active Substances

The literature review is devoted to the analysis of numerous studies that have formed the basis for creating ideas about the diffuse endocrine system. In addition to the main endocrine glands, also there are cellular accumulations and individual cells that produce various hormones and biologically active substances. It is established that, in particular, in the organs of the gastrointestinal tract, starting from the esophagus and to the terminal parts of the large intestine, there are several types of endocrine cells with these functions. Most of them are in the pancreas, antrum of the stomach, duodenum, the initial part of the intestine, in the liver. Excessive secretory activity of these cells can cause the development of pathological clinical syndromes, characterized by the effect of the corresponding hormones. The morphological substrate of such syndromes may be tumors or diffuse hyperplasia of the corresponding cells. The author considers the pancreas as an integral part of the diffuse endocrine system, as specific endocrine functions in it perform numerous accumulations (islets of Langerhans) or individual cells. The review of the numerous neuroendocrine tumors of the gastrointestinal tract examines in detail the characteristics of some of them in historical and clinical aspects, in particular insulinoma as the most common and well-studied tumor. Glucagonoma is also considered as a neuroendocrine tumor derived from α-cells of the pancreas, is a kind of insulinoma antagonist, as it secretes an excess of the hormone glucagon, causing the development of hyperglycemic clinical syndrome in contrast to hypoglycemic, caused by insulin. It is a rare tumor and its consideration after insulinoma can be explained by the antagonistic nature of the action of hormones produced by these tumors. In the group of neuroendocrine tumors of the pancreas, glucagonoma follows the frequency of insulinoma and gastrinoma.

scholarly journals On the history and some characteristics of neuroendocrine tumors of the gastrointestinal tract. Neuroendocrine tumors of the pancreas. Part 2

2021 ◽  
pp. 70-81
Author(s):  
S. I. Rybakov
Keyword(s):  
Gastrointestinal Tract ◽  
Neuroendocrine Tumors ◽  
Endocrine System ◽  
Secretory Activity ◽  
Clinical Syndrome ◽  
Biologically Active ◽  
Clinical Aspects ◽  
Clinical Syndromes ◽  
Diffuse Endocrine System ◽  
Active Substances

The literature review presents the analysis of numerous studies that have formed the basis for creating ideas about the diffuse endocrine system,namely existence of the cellular accumulations and individual cells that produce various hormones and biologically active substances in addition to the main endocrine glands. Several types of endocrine cells with these functionshave been established, in particular, in the organs of the gastrointestinal tract, starting from the esophagus and up to the terminal parts of the large intestine. Most of them are contained in the pancreas, antrum of the stomach, duodenum, the initial part of the intestine, in the liver. Excessive secretory activity of these cells can cause the development of pathological clinical syndromes, characterized by the effects of the corresponding hormones. The tumors or diffuse hyperplasia of the corresponding cellsmay present morphological substrate of such syndromes. The author considers the pancreas as an integral part of the diffuse endocrine system, as specific endocrine functions in it perform numerous accumulations (islets of Langerhans) or individual cells. The review of the numerous neuroendocrine tumors of the gastrointestinal tract examines in detail the characteristics of some of them in historical and clinical aspects, in particular Zollinger—Ellison syndrome as the most common and well-studied tumor. Glucagonoma is also considered as a neuroendocrine tumorderived from α-cells of the pancreas, is a kind of insulinoma antagonist, as it secretes an excess of the hormone glucagon, causing the development of hyperglycemic clinical syndrome in contrast to hypoglycemic, caused by insulin. It is a rare tumor and its consideration after insulinoma can be explained by the antagonistic nature of the action of hormones produced by these tumors. In the group of neuroendocrine tumors of the pancreas, glucagonoma follows the frequency of insulinoma and gastrinoma.

Treatment of cancer

2018 ◽  
Author(s):  
David Cutter ◽  
Martin Scott-Brown
Keyword(s):  
Management Strategies ◽  
Colon Adenocarcinoma ◽  
Management Plan ◽  
Treatment Modalities ◽  
Management Approach ◽  
Best Management ◽  
Appropriate Treatment ◽  
Wide Range ◽  
Specialist Nurses ◽  
The Individual

The variety of conditions that are considered to be ‘cancer’ is extremely wide, with marked variation in the management approach from disease to disease. A common feature in the management of malignant conditions, however, is the involvement of a wide range of medical professionals at different stages of the patient pathway. This commonly includes physicians, surgeons, radiologists, pathologists, medical oncologists, radiation oncologists, and specialist nurses, as well as a plethora of other allied disciplines. As such, a practice that has been widely adopted is to work as a multidisciplinary team (MDT), with regular meetings to decide the appropriate treatment for each patient with a cancer diagnosis, on an individual and case-by-case basis. The main treatment modalities for the treatment of cancer are surgery, radiotherapy, and chemotherapy. While these are often combined to form a multimodality therapy, they are all, in isolation, potentially radical (curative) therapies for certain conditions. For example, surgery (in the case of a Stage I colon adenocarcinoma), radiotherapy (in the case of early laryngeal squamous cell carcinoma), and chemotherapy (in the case of acute lymphoblastic leukaemia) are all curative as single-modality treatments. It is commonly the case, however, for a patient to require more than one mode of therapy to achieve the best outcome, for example a combination of surgery, chemotherapy, and radiotherapy for early breast cancer. It can also be the case that two or more different management strategies are thought to give equivalent oncological results, for example surgery or radiotherapy for early prostate cancer. In this situation, the MDT and the patient need to decide on the ‘best’ management plan for the individual, based on their personal and professional opinions and on the differing toxicity profiles of the alternate treatments.

Pancreatic Neuroendocrine Tumors: Presentation, Management, and Outcomes

2009 ◽  
Vol 75 (10) ◽  
pp. 1025-1029 ◽  
Author(s):  
Nicholas N. Nissen ◽  
Amanda S. Kim ◽  
Run Yu ◽  
Edward M. Wolin ◽  
Marc L. Friedman ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Pancreatic Resection ◽  
Survival Rates ◽  
Pancreatic Neoplasm ◽  
Disease Free Survival ◽  
Treatment Modalities ◽  
Entire Group ◽  
Pancreatic Neuroendocrine Tumors ◽  
Multiple Treatment ◽  
Systemic Treatments

Pancreatic neuroendocrine tumors (pNETs) are an uncommon pancreatic neoplasm. We reviewed the presentation, management, and outcome of patients with pNETs treated at a single center by a multidisciplinary approach between 2004 and 2008. Over this time period, 154 patients with carcinoid and neuroendocrine tumors were treated, which included 46 patients (30% of total) with pNETs. The most common presentations included abdominal pain (20 of 46 [43%]), systemic symptoms such as hypoglycemia (15 of 46 [33%]), and incidental mass (7 of 46 [15%]). Fourteen patients had functional tumors. At the time of diagnosis, 22 patients (48%) presented without metastases and 24 (52%) had metastatic disease. Median follow up for the entire group was 42 months. All patients with nonmetastatic pNET underwent pancreatic resection with 95 per cent postoperative survival. Overall survival in this group at 3 years was 86 per cent and disease-free survival was 81 per cent. In patients presenting with metastatic pNET, multiple treatment modalities were used, including liver resection or ablation (n = 15), hepatic chemoembolization (n = 17), pancreatic resection (n = 12), and systemic treatments (n = 7). Three-year survival was 70 per cent. Pancreatic resection results in greater than 80 per cent 3-year survival in nonmetastatic pNET. In patients presenting with metastatic pNET, excellent survival rates are also achievable using a multidisciplinary multimodal approach.

Temozolomide and capecitabine (CAPTEM) is effective in metastatic well-differentiated gastrointestinal neuroendocrine tumors.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 366-366
Author(s):  
İzzet Dogan ◽  
Didem Tastekin ◽  
Senem Karabulut ◽  
Burak Sakar
Keyword(s):  
Prognostic Factors ◽  
Neuroendocrine Tumors ◽  
Cox Regression ◽  
Somatostatin Receptor ◽  
Ki 67 ◽  
Cox Regression Analysis ◽  
Number Of Patients ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Metastatic Sites

366 Background: The study aimed to evaluate patients' outcomes and prognosis with metastatic gastrointestinal neuroendocrine tumors (mgNET) who treated temozolomide and capecitabine (CAPTEM). Methods: The data of forty-three patients were retrospectively evaluated. Clinicopathological features and treatment approaches were recorded. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS). Prognostic factors were assessed with Cox-regression analysis. Results: Median age was 59 (27-85) years. The number of male and female patients was 23 (%53.5) and 20 (%46.5), respectively. Pancreas (%51.2) was the most common site of the tumor. The number of patients with well- and poorly-differentiated mgNET was 38 (%88.4) and 5 (%11.6), respectively. The most common metastatic sites were liver (%62.8), lymph node (%58.1), and bone (%18.6). Eleven (%25.6) of the patients previously had undergone surgery, and some patients received radiotherapy (%9.5), chemotherapy (%19), and nuclear therapy (%9.3). Also, patients received octreotide (%86) or lanreotide (%14) with CAPTEM. In patients with well-differentiated mgNET, median PFS was 17.4 months, and disease control ratio %79.4 (%3-complete response, %38.2-partial response, and %38.2-stable response). No response observed in patients with poorly differianted mgNET, and the median PFS was calculated as 4.5 months. Grade 1-2 toxicity was observed in 34 (%79.1) of the patients, and grade 3-4 toxicity in 8 (%18.6). Four (%9.5) patients discontinued therapy for the toxicity. The most common toxicities were anemia (%37.2), thrombocytopenia (%25.6), and fatigue (%16.3). At a median follow-up of 33.8 (2.9-172.73) months, the ratio of five-years OS was %61. In multivariate analysis; gender (p=0.008), age (p=0.007), and Ki-67 levels (p=0.011) were a statistically significant for OS. However, the site of the tumor (p=0.186), number of metastatic sites (p=0.255), and type of somatostatin receptor ligand (p=0.903) were not. Conclusions: In the study, we showed that CAPTEM + somatostatin receptor ligands (octreotide or lanreotide) were effective and well-tolerated in patients with well-differentiated mgNET. But, it was not effective in patients with poorly-differentiated mgNET. Male gender, aged over 60 years, and tumor with a high level of Ki-67 were negative prognostic factors.

Neuroendocrine tumors in children and young adults: Incidence, survival, and prevalence in the United States

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22120-e22120
Author(s):  
M. S. O'Dorisio ◽  
P. Navalkele ◽  
T. M. O'Dorisio ◽  
C. F. Lynch
Keyword(s):  
United States ◽  
Young Adults ◽  
Young People ◽  
Neuroendocrine Tumors ◽  
Endocrine System ◽  
The United States ◽  
Seer Data ◽  
Children And Young Adults ◽  
Diffuse Endocrine System ◽  
Incidence Prevalence

e22120 Background: Neuroendocrine tumors (NET) arising from the diffuse endocrine system are thought to be quite rare in children and young adults. However, a surprising number of young people have been referred to our neuroendocrine tumor clinic and the NCI has targeted NET as a high priority for development of new diagnostic and therapeutic options. This analysis of the SEER database was undertaken to determine the incidence, prevalence, and survival of NET in young people. Their incidence, prevalence, and survival were compared with neuroblastoma, a related pediatric malignancy arising in the neural crest. Methods: The SEER data were obtained from 9 standard SEER registries for the diagnosis years of 1975 to 2004 using SEER*Stat version 6.4.4. ICD-9 codes related to neuroendocrine tumors and to neuroblastoma were characterized as to patient age, gender, racial and ethnic background, stage, grade, histology, incidence, survival, and prevalence. Results: Neuroendocrine tumors occur more often in females among children and young adults with the most common sites being bronchial, ovarian, and breast. The overall incidence of neuroendocrine tumors was lower than for neuroblastoma in the age range 0–30 years. However, the 30 year limited prevalence of neuroendocrine tumors in the 9 SEER registries was 698 compared to 881 for neuroblastoma. This extrapolated to over 7000 children and young adults with neuroendocrine tumors across the United States. Survival rate of young people with neuroendocrine tumors declined from 84% in 1975–1986 to 80% in the 1987–2004 era. Conclusions: These results indicate that neuroendocrine tumors constitute an unrecognized cancer threat to children and young adults. Survival of children and young adults with neuroendocrine tumors has decreased over the past 30 years in the United States. We recommend the establishment of centers of care for children and young adults diagnosed with neuroendocrine tumors with the expectation that earlier diagnosis coupled with targeted therapies will decrease the incidence of metastatic disease and improve survival. No significant financial relationships to disclose.

scholarly journals Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future

2019 ◽  
Vol 20 (12) ◽  
pp. 3049 ◽  
Author(s):  
Anna Kathrin Stueven ◽  
Antonin Kayser ◽  
Christoph Wetz ◽  
Holger Amthauer ◽  
Alexander Wree ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Clinical Symptoms ◽  
Somatostatin Receptor ◽  
Randomized Study ◽  
Phase Iii ◽  
Response To Treatment ◽  
Treatment Modalities ◽  
Controlled Study ◽  
Somatostatin Analogue ◽  
Significant Prolongation

In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has been a mainstay of antisecretory therapy in functioning neuroendocrine tumors, which cause various clinical symptoms depending on hormonal hypersecretion. Beyond symptomatic management, recent research demonstrates that SSAs exert antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2). Both the PROMID (placebo-controlled, prospective, randomized study in patients with metastatic neuroendocrine midgut tumors) and the CLARINET (controlled study of lanreotide antiproliferative response in neuroendocrine tumors) trial showed a statistically significant prolongation of time to progression/progression-free survival (TTP/PFS) upon SSA treatment, compared to placebo. Moreover, the combination of SSA with peptide receptor radionuclide therapy (PRRT) in small intestinal NETs has proven efficacy in the phase 3 neuroendocrine tumours therapy (NETTER 1) trial. PRRT is currently being tested for enteropancreatic NETs versus everolimus in the COMPETE trial, and the potential of SSTR-antagonists in PRRT is now being evaluated in early phase I/II clinical trials. This review provides a synopsis on the pharmacological development of SSAs and their use as antisecretory drugs. Moreover, this review highlights the clinical evidence of SSAs in monotherapy, and in combination with other treatment modalities, as applied to the antiproliferative management of neuroendocrine tumors with special attention to recent high-quality phase III trials.

Epidemiology and treatment of high-grade gastrointestinal neuroendocrine tumors (HG-GI-NETs).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 421-421
Author(s):  
Olatunji B. Alese ◽  
Renjian Jiang ◽  
Walid Labib Shaib ◽  
Christina Sing-Ying Wu ◽  
Mehmet Akce ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Proportional Hazards ◽  
Management Strategies ◽  
Survival Rates ◽  
Multivariable Analysis ◽  
High Volume ◽  
Cox Proportional Hazards ◽  
High Grade ◽  
Short Treatment ◽  
Academic Center

421 Background: High grade neuroendocrine tumors of the gastrointestinal tract are rare tumors. Management strategies are modeled after small cell lung cancer (SCLC). Treatment patterns and outcomes have not been studied. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2013. Univariate and multivariate testing was done to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between patient characteristics and survival. Results: A total of 1,861 patients were identified for the 10 years of the study. The mean age was 63 years (SD±13), with a male preponderance (53.3%). The vast majority of patients (78.1%) were non-Hispanic Whites. The most common primary sites were pancreas (PNET = 19.4%), large intestine (18.1%), esophagus (17.8%) and rectum (15.5%). About 27.9% of the cases were resectable at the time of diagnosis, and distribution across stages 1-IV was 6.6%, 10.5%, 18% and 64.6% consecutively. Liver was a common site of metastases (50.4%), followed by bone (11.3%) and lungs (10.8%). Only 3.5% of the patients had brain metastases. On univariable analysis, age < 65years (HR 0.72; 0.66-0.8; p < 0.001) and treatment at an academic center (HR 0.88; 0.79-0.99; p < 0.034) were associated with improved survival. Multivariable analysis confirmed prognostic advantage of treatment at an academic center. Patients treated with chemotherapy had a median overall survival (OS) of 11.2 months, compared with 1.7 months for those who did not. The median OS for high grade PNET was 6 months, compared to 9.9 months for other HG-GI-NETs. One year and 5-year survival rates were 27.5% vs. 41% and 4.5% vs. 12.3% respectively. Conclusions: This is the largest series of HG-GI-NET. Almost two-thirds of the cases present with metastatic disease. Pattern of metastasis differs from SCLC. Survival is short. Treatment at high volume academic center, younger age and use of chemotherapy are associated with improved survival.

Highlights of the biology of endocrine tumours of the gut and pancreas.

2003 ◽  
pp. 427-436 ◽  
Author(s):  
G Rindi ◽  
C Bordi
Keyword(s):  
Growth Factors ◽  
Endocrine System ◽  
Low Grade ◽  
High Grade ◽  
Bioactive Substances ◽  
Endocrine Tumours ◽  
Genetic Abnormalities ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Diffuse Endocrine System

Originating from cells of the diffuse endocrine system the endocrine tumours of the gut and the pancreatic tract are rare entities characterized by a common phenotypic aspect and producing several bioactive substances including growth factors. Two major categories are identified: well-differentiated and poorly differentiated tumours. The clinical behaviour varies ranging from benign to low grade malignant for well-differentiated tumours/carcinomas to high grade malignant for poorly differentiated carcinomas. The two major categories of well-differentiated and poorly differentiated tumours display distinct phenotypes and genetic backgrounds possibly supporting distinct histogenesis. Genetic abnormalities associated with either induction or progression of tumours may vary depending on the site of origin.

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