Carcinoid-syndrome: recent advances, current status and controversies

Ito, Tetsuhide; Lee, Lingaku; Jensen, Robert T.

doi:10.1097/med.0000000000000376

Cited by 96 publications

(51 citation statements)

References 195 publications

(469 reference statements)

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Section: Efficacy Of Everolimusmentioning

confidence: 99%

“…In the management of F-NETs, control of the hormone hypersecretory syndrome is a key factor for maintaining quality of life (QOL) and also survival in many cases[103,104]. Carcinoid-syndrome is the most frequent ectopic hormonal syndromes in NETs[104], and SSA is the standard initial treatment [104–106]. In the recent phase III TELESTAR trial, telotristat ethyl, a peripheral tryptophan hydroxylase inhibitor, in combination with SSA demonstrated significant reduction in bowel movement frequency in NETs with SSA refractory carcinoid syndrome[30].…”

Section: Efficacy Of Everolimusmentioning

confidence: 99%

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Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

Lee

Ito

Jensen

2018

Expert Opinion on Pharmacotherapy

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Introduction: Since the initial approval of everolimus in 2011, there have been a number of important changes in therapeutic/diagnostic modalities as well as classification/staging systems of neuroendocrine tumors (NETs), which can significantly impact the use of everolimus in patients with advanced NETs. Areas covered: The efficacy of everolimus monotherapy and combination therapy demonstrated in clinical studies involving patients with advanced NETs are reviewed. Several factors affecting everolimus’ use are described including: the development and routine use of NET classification/staging systems; widespread use of molecular imaging modalities; side-effects; drug resistance; and the availability of other treatment options. Furthermore, the current position of everolimus in the treatment approach is discussed, taking into account the recommendations from the recent guidelines. Expert opinion: Although everolimus demonstrated its high efficacy and tolerability in the RADIANT trials and other clinical studies, there still remain a number of controversies related to everolimus treatment in the management of NETs. The synergistic anti-growth effect of other agents in combination with everolimus or its effect on overall survival have not been established. The appropriate order of the use of everolimus in the treatment of advanced NETs still remains unclear, which needs to be defined in further studies and will be addressed in the new guidelines.

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Section: Efficacy Of Everolimusmentioning

confidence: 99%

Section: Efficacy Of Everolimusmentioning

confidence: 99%

Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

Lee

Ito

Jensen

2018

Expert Opinion on Pharmacotherapy

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“…The hallmark symptoms of carcinoid syndrome are flushing and diarrhea; atypical signs and symptoms can include wheezing, abdominal pain, valvular heart disease, telangiectasias, pellagra, and the complications of mesenteric fibrosis, including ureteral obstruction, bowel obstruction, and bowel ischemia [1]. These symptoms are mediated by the release of serotonin (5-HT), histamine, kallikrein, prostaglandins, and tachykinins [2]. The diagnosis of CS requires these symptoms and corresponding elevations in lab tests.…”

Section: Introductionmentioning

confidence: 99%

Carcinoid Syndrome: A Review

Gade¹,

Olariu²,

Douthit³

2020

Cureus

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Carcinoid syndrome (CS) is a paraneoplastic syndrome caused by the release of serotonin and other substances from well-differentiated neuroendocrine tumors (NETs). The hallmark symptoms of carcinoid syndrome are flushing and diarrhea; atypical signs and symptoms can include wheezing, abdominal pain, valvular heart disease, telangiectasias, pellagra, and the complications of mesenteric fibrosis, including ureteral obstruction, bowel obstruction, and bowel ischemia. These symptoms are mediated by the release of serotonin (5-HT), histamine, kallikrein, prostaglandins, and tachykinins. The diagnosis of CS requires these symptoms and corresponding elevations in lab tests. Treatment options include surgery and medical management with somatostatin analogs.

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“…e most common symptom is diarrhoea which is reported in around 80% of patients [4,17,18]. e diarrhoea is secretory with a frequency of a least 3 bowel motions a day and is due to increased gastrointestinal motility stimulated by hormones produced by the NEN [19,20].…”

Section: Signs and Symptoms Of Carcinoid Syndromementioning

confidence: 99%

Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome

Clement

Ramage

Srirajaskanthan

2020

Journal of Oncology

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Carcinoid syndrome (CS) develops in patients with hormone-producing neuroendocrine neoplasms (NENs) when hormones reach a significant level in the systemic circulation. The classical symptoms of carcinoid syndrome are flushing, diarrhoea, abdominal pain, and wheezing. Neuroendocrine neoplasms can produce multiple hormones: 5-hydroxytryptamine (serotonin) is the most well-known one, but histamine, catecholamines, and brady/tachykinins are also released. Serotonin overproduction can lead to symptoms and also stimulates fibrosis formation which can result in development of carcinoid syndrome-associated complications such as carcinoid heart disease (CaHD) and mesenteric fibrosis. Transforming growth factor beta (TGF-β) is one of the main factors in developing fibrosis, but platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF2), and connective tissue growth factor (CTGF or CCN2) are also related to fibrosis development. Treatment of CS focuses on reducing serotonin levels with somatostatin analogues (SSA’s). Telotristat ethyl and peptide receptor radionuclide therapy (PRRT) have recently become available for patients with symptoms despite being established on SSA’s. Screening for CaHD is advised, and early intervention prolongs survival. Mesenteric fibrosis is often present and associated with poorer survival, but the role for prophylactic surgery of this is unclear. Depression, anxiety, and cognitive impairment are frequently present symptoms in patients with CS but not always part of their care plan. The role of antidepressants, mainly SSRIs, is debatable, but recent retrospective studies show evidence for safe use in patients with CS. Carcinoid crisis is a life-threatening complication of CS which can appear spontaneously but mostly described during surgery, anaesthesia, chemotherapy, PRRT, and radiological procedures and may be prevented by octreotide administration.

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Carcinoid-syndrome: recent advances, current status and controversies

Abstract: There have been numerous advances in all aspects of the carcinoid-syndrome, which is the most common functional syndrome neuroendocrine tumors produce. These advances are leading to new approaches to the management of these patients and in some cases to new controversies.

Cited by 96 publications

References 195 publications

Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

Carcinoid Syndrome: A Review

Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome

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