Digestive Neuroendocrine Tumors Research Articles

TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system

The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor–node–metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.

Screening for activated kinases reveals constitutive stimulation of cAMP response element binder (CREB) and protein kinase B (PKB/Akt) in digestive neuroendocrine tumors (dNETs)

Screening for activated kinases reveals constitutive stimulation of cAMP response element binder (CREB) and protein kinase B (PKB/Akt) in digestive neuroendocrine tumors (dNETs)

Tumeur carcinoïde de l’intestin grêle

Carcinoïd tumors are non-pancreatic digestive neuroendocrine tumors well differentiated. Most of time they are developed from enterochromaffin cells of the digestive tract. Most of them are localized in ileum, rectum, stomach and appendix. Only bronchi are a frequent extra-digestive localization (20 to 25%). Most of these tumors are asymptomatic and discovered incidentally during a laparotomy or secondary to the exploration of a carcinoïd syndrom. From a case report and a recent review of literature, diagnosis, histology and treatment of small bowel carcinoïd tumors are summarized.

Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system

This consensus report gives a detailed description of the use of somatostatin analogs in the management of neuroendocrine tumors of the gastroenteropancreatic system. As background information we have outlined critical aspects of the pathology, the use of tumor markers, a definition of functional and non-functional digestive neuroendocrine tumors, different imaging modalities, surgical considerations, liver embolization and the use of cytotoxic drugs as well as interferon. Included in the report is an overview of somatostatin, somatostatin analogs and its receptor expression in different neuroendocrine tumors. It will also define the binding affinities of different somatostatin analogs to the five different subtypes of somatostatin receptor. We compare the efficacy of octreotide and lanreotide in reducing diarrhea and flushing. Side-effects are described and we provide practical information on somatostatin analog treatment.

Digestive neuroendocrine tumours: diagnosis and treatment in Italy. A survey by the Oncology study Section of the Italian Society of Gastroenterology (SIGE)

Background. New insights in the diagnosis and treatment of digestive neuroendocrine tumours have prompted a renewed interest in these rare and complex diseases. Aim. To establish how many new cases of digestive neuroendocrine tumours were diagnosed, and how they were treated, at gastroenterological centres across Italy during a two-year period (1997–1998). Methods. The 12 centres taking part filled in a data collection form reporting type of tumour, methods of diagnosis and therapeutic strategies adopted in each case. Data were collected and analysed by the authors of the present report. Results. Data refer to 98 patients, 22 with functioning and 76 with non-functioning digestive neuroendocrine tumours [5D carcinoids, 48 pancreatic endocrine tumour syndromes]. Primary tumours were localised in 96% (38% with metastases) of non-functioning and 81% (50% with metastases) of functioning tumours. These were surgically removed in >80% of patients in both groups. Somatostatin analogue treatment, with or without interferon, was administered in 35% of patients, while chemotherapy was used in 9% and 23% of functioning and non-functioning tumours, respectively. The imaging study always included a computed tomography scan (20% helical computed tomography). Magnetic resonance and somatostatin receptor scintigraphy were also performed, the former in 41% and 21% of the two (functioning and non-functioning tumour) groups, the latter in 45% and 30%. Conclusions. The number of functioning digestive neuroendocrine tumours reported was lower than expected. Surgery plays a major role in the treatment of these tumours in all centres. Overall, in only a small number of patients was a multidisciplinary approach applied.

Could somatostatin receptor subtypes (sst) expression be considered as positive prognostic factor in patients with digestive neuroendocrine tumors (dNETs)?

Could somatostatin receptor subtypes (sst) expression be considered as positive prognostic factor in patients with digestive neuroendocrine tumors (dNETs)?

Could somatostatin receptor subtypes (sst) expression be considered as positive prognostic factor in patients with digestive neuroendocrine tumors (dNETs)?

Could somatostatin receptor subtypes (sst) expression be considered as positive prognostic factor in patients with digestive neuroendocrine tumors (dNETs)?

Could somatostatin receptor subtypes (sst) expression be considered as positive prognostic factors in patients with digestive neuroendocrine tumours (dNETs)?

Could somatostatin receptor subtypes (sst) expression be considered as positive prognostic factors in patients with digestive neuroendocrine tumours (dNETs)?

Use of chromogranin a as specific serum marker in functioning and non-functioning digestive neuroendocrine tumors

Use of chromogranin a as specific serum marker in functioning and non-functioning digestive neuroendocrine tumors

Staging digestive neuroendocrine tumors (dNETs): Comparative role of somatostatin receptors scintigraphy and helical CT (hCT)

Staging digestive neuroendocrine tumors (dNETs): Comparative role of somatostatin receptors scintigraphy and helical CT (hCT)

Relationship between somatostatin receptor subtypes (SST) and clinical outcome on patients with digestive neuroendocrine tumors (DNETS)

Relationship between somatostatin receptor subtypes (SST) and clinical outcome on patients with digestive neuroendocrine tumors (DNETS)

Combined helical CT (hCT) and somatostatin receptor scintigraphy (SRS) improve the diagnosis in patients with digestive neuroendocrine tumors (dNET)

Combined helical CT (hCT) and somatostatin receptor scintigraphy (SRS) improve the diagnosis in patients with digestive neuroendocrine tumors (dNET)

High sensitivity of chromogranin a (CgA) as serum marker of functioning and non-functioning digestive neuroendocrine tumors

High sensitivity of chromogranin a (CgA) as serum marker of functioning and non-functioning digestive neuroendocrine tumors

Site-Specific Epithelial-Mesenchymal Interactions in Digestive Neuroendocrine Tumors: An Experimental in Vivo and in Vitro Study

Little is known about the functional interactions between digestive neuroendocrine tumor cells and their stromal microenvironment. The focus of our study is whether mesenchymal cells modulate peptide expression, cell proliferation, and invasiveness in digestive neuroendocrine tumor cells. We designed an experimental in vivo and in vitro study using the mouse enteroendocrine cell line STC-1. In vivo, STC-1 cells were injected subcutaneously in 18 immunosuppressed newborn rats. At day 21, all animals presented poorly differentiated neuroendocrine tumors with lung metastases. Subcutaneous tumors were usually limited by a capsule containing basement membrane components and myofibroblasts that presented a low mitotic index. Lung tumors were devoid of capsule and poor in myofibroblasts, and their mitotic index was high. The profile of peptide expression in STC-1 tumors was different from that of cultured STC-1 cells. In vitro, STC-1 cells were cultured with fibroblasts of different origins, including dermis, lung, digestive tract, and liver. Based on their origin, myofibroblasts differentially modulated hormone synthesis, proliferation, spreading, and adhesion of STC-1 cells. In conclusion, our results show that site-specific functional interactions between mesenchymal and neuroendocrine cells may contribute to modulating the behavior of digestive neuroendocrine tumors, depending on their growth site.

Expression of vascular endothelial growth factor in digestive neuroendocrine tumours

Angiogenesis is a complex multistep process essential for tumour growth. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and vascular permeability-inducing agent. Recent studies have shown that VEGF expression is correlated to microvessel density and tumour progression. The aim of this study was to analyse VEGF expression in a series of gastrointestinal neuroendocrine tumours. Surgical specimens from 28 gastrointestinal carcinoids and 20 pancreatic endocrine tumours were examined for VEGF expression by immunohistochemistry. Intense cytoplasmic staining for VEGF was observed in several cells of the islets of Langerhans and in neuroendocrine cells of normal digestive mucosa. All midgut carcinoids showed strong VEGF expression in tumoral cells. Positive VEGF immunostaining was observed in 16 of 20 neuroendocrine pancreatic tumours but it was usually much lower than in midgut carcinoids. Western blotting analysis in eight cases identified a major band at 30-32 kDa. No correlation between VEGF expression and tumour stage was found. This study demonstrates that neuroendocrine cells are a major source of VEGF, particularly in midgut carcinoids. This finding suggests that the presence of VEGF may be required to maintain the differentiated state of capillary vessels in these hypervascular tumours. Such secretion, in conjunction with the other growth factors synthesized by these neuroendocrine tumours, may have an important role in tumour growth.