Medical management of secretory syndromes related to gastroenteropancreatic neuroendocrine tumours

Abstract

Although recent epidemiological evidence indicates that the prevalence of non-functioning gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) is rising, a significant number of GEP-NETs still present with symptoms related to the secretion of biologically active substances leading to the development of distinct clinical syndromes. In the past, these syndromes were associated with substantial morbidity and mortality due to the lack of specific therapies; however, since the introduction of long-acting somatostatin analogues and medications such as proton pump inhibitors, their control has been greatly improved. As a result, nowadays, the main cause of morbidity and mortality in GEP-NETs is mostly directly related to tumour growth and the extent of metastatic disease. However, in some patients with functioning tumours and extensive disease, control of the secretory syndrome still remains problematic, necessitating the employment of several cytoreductive techniques, which may not always be sufficient. Recently, new agents directed against tumour growth, or exerting increased binding activity to receptors expressed in these tumours, or interfering with the synthetic pathway of some of the compounds secreted by these tumours, have been developed. Since there are no specific guidelines addressing the totality of the management of the secretory syndromes related to GEP-NETs, this review aims at critically analysing the medical management of previously recognised secretory syndromes; it also addresses areas of uncertainty, assesses the newer therapeutic developments and also addresses recently described but poorly characterised secretory syndromes related to GEP-NETs.

The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8‐institution study from the US Neuroendocrine Tumor Study Group

“…These findings suggest that symptom persistence after surgery may serve as a strong surrogate marker for persistence of tumor cells within the body. Although there is no current standard adjuvant therapy for patients with functional NETs, as the therapeutic armamentarium grows, it is feasible that symptom persistence after the surgery may be a reasonable selection criterion for patients in future clinical trials . Even more importantly, however, this study demonstrates that patients with symptom persistence may warrant more frequent radiographical surveillance to detect earlier disease recurrence …”

Paediatric VIPoma: A Jamboree of Electrolytes

“…Preoperative octreotide therapy (somatostatin analogue) is the cornerstone of management of VIPoma patients (5). Octreotide in a dose of 250-450 µg day -1 has been observed to bring about a 60% symptomatic, 70% biochemical and 5%-10% tumour response.…”

Paraneoplastic endocrine syndromes

“…Ectopically produced bioactive substances from endocrine and non-endocrine neoplasms leading to endocrine PNS are mostly peptides and hormones, and less commonly biogenic amines, steroids or thyroid hormones (Kaltsas et al 2010, Dimitriadis et al 2016. The symptoms are produced following the direct secretion of these substances from the tumour to the circulation, although they may also exert paracrine and autocrine effects.…”