Use of healthcare REsources and associated COsts in controlled versus uncontrolled carcinoid SYndrome in patients with neuroendocrine tumours: the RECOSY study.

PURPOSE: To report healthcare resource use and associated costs in controlled versus uncontrolled carcinoid syndrome (CS) in patients with neuroendocrine tumours. METHODS: A cross-sectional, non-interventional multicentre study was conducted with retrospective data analysis. Resource use was compared between two patient groups: those with controlled CS (> 12 months with no uncontrolled CS episodes) and uncontrolled CS (< 12 months since last uncontrolled episode). Patients were matched for age, sex, and origin and grade of tumour. When no matching patients were available, data from deceased patients were used. Information on healthcare resource use came from review of medical records, patient history and physician reports. Working capacity was assessed using the Work Productivity and Activity Impairment General Health questionnaire. RESULTS: Twenty-six university hospitals in Spain participated, between July 2017 and April 2018. 137 patients were enrolled; 104 were analysed (2 groups of 52). Patients with uncontrolled CS had 10 times more emergency department (ED) visits (mean 1.0 vs 0.10 visits; P = 0.0167), were more likely to have a hospital admission (40.4% vs 19.2%; P = 0.0116) and had longer hospital stays (mean 7.87 vs 2.10 days; P = 0.0178) than those with controlled CS. This corresponded to higher annual hospitalisation costs (mean €5511.59 vs €1457.22; P = 0.028) and ED costs (€161.25 vs €14.85; P = 0.0236). The mean annual total healthcare costs were 60.0% higher in patients with uncontrolled than controlled CS (P = NS). CONCLUSION: This study quantifies higher health resource use, and higher hospitalisation and ED costs in patients with uncontrolled CS. Better control of CS may result 3in lower medical costs.

Carcinoid syndrome: update on the pathophysiology and treatment.

Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment. While these agents provide significant relief from carcinoid syndrome symptoms, there is inevitable clinical progression, and new therapeutic interventions are needed. More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. Given the complexity involving the origin, diagnosis and management of patients with carcinoid syndrome, we have undertaken a comprehensive review to update information about the pathophysiology, diagnostic tools and treatment sequence of this syndrome, which currently comprises a multidisciplinary approach.

Carcinoid syndrome: update on the pathophysiology and treatment

Approximately 30-40% of patients with well-differentiated neuroendocrine tumors present with carcinoid syndrome, which is a paraneoplastic syndrome associated with the secretion of several humoral factors. Carcinoid syndrome significantly and negatively affects patients' quality of life; increases costs compared with the costs of nonfunctioning neuroendocrine tumors; and results in changes in patients' lifestyle, such as diet, work, physical activity and social life. For several decades, patients with neuroendocrine tumors and carcinoid syndrome have been treated with somatostatin analogues as the first-line treatment. While these agents provide significant relief from carcinoid syndrome symptoms, there is inevitable clinical progression, and new therapeutic interventions are needed. More than 40 substances have been identified as being potentially related to carcinoid syndrome; however, their individual contributions in triggering different carcinoid symptoms or complications, such as carcinoid heart disease, remain unclear. These substances include serotonin (5-HT), which appears to be the primary marker associated with the syndrome, as well as histamine, kallikrein, prostaglandins, and tachykinins. Given the complexity involving the origin, diagnosis and management of patients with carcinoid syndrome, we have undertaken a comprehensive review to update information about the pathophysiology, diagnostic tools and treatment sequence of this syndrome, which currently comprises a multidisciplinary approach.

Central nervous system plus autonomic nervous system disorders responsible for gastrointestinal and pancreatobiliary diseases.

Clinical digestive disorders depend on the non-adequate coupling of functioning of the gastrointestinal tract with that of its affluent systems, namely, the pancreatic exocrine and the hepato-biliary secretions. The secretion of gastrointestinal hormones is monitored by the peripheral autonomic nervous system. However, the latter is regulated by the central nervous system (CNS) circuitry localized at the medullary pontine segment of the CNS. In turn, both parasympathetic and adrenergic medullary circuitries are regulated by the pontine A5 noradrenergic (NA) and the dorsal raphe serotonergic nuclei, respectively. DR-5HT is positively correlated with the C1-Ad medullary nuclei (responsible for adrenal gland secretion), whereas the MR-5HT nucleus is positively correlated with the A5-NA pontomedullary nucleus. The latter is responsible for neural sympathetic activity (sympathetic nerves). Both types of sympathetic activities maintain an alternation with the peripheral parasympathetic branch, which is positively correlated with the enterochromaffin cells that secrete serotonin. Serotonin displays hormonal antagonism to the circulating catecholamines.

Carcinoid syndrome: diagnosis and medical management

Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what combination of bioactive substances is secreted. Midgut carcinoid can present with the carcinoid syndrome in the presence of liver metastases. Its most typical clinical manifestations include cutaneous flushing and diarrhea. A nonspecific biochemical tumor marker for carcinoid tumors is serum chromogranin A and a specific marker for the carcinoid syndrome is the increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA). Localizing studies in carcinoid tumors/syndrome are: transabdominal ultrasonography (US), endoscopy, endoscopic US, videocapsule endoscopy, computerized tomography, magnetic resonance imaging, selective abdominal angiography, 111In-pentetreotide scintigraphy (and intraoperative radionuclide probe), 123I (131I)-metaiodobenzylguanidine (MIBG) scintigraphy, bone scintigraphy and 11C-5-HT positron emission tomography (PET). Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs, interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)-embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation of liver metastases, cryosurgery of liver metastases, occasionally liver transplantation, radiotherapy-coupled somatostatin analogs, 131I-MIBG and occasionally chemotherapy.

Carcinoid syndrome: diagnosis and medical management.

Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what combination of bioactive substances is secreted. Midgut carcinoid can present with the carcinoid syndrome in the presence of liver metastases. Its most typical clinical manifestations include cutaneous flushing and diarrhea. A nonspecific biochemical tumor marker for carcinoid tumors is serum chromogranin A and a specific marker for the carcinoid syndrome is the increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA). Localizing studies in carcinoid tumors/syndrome are: transabdominal ultrasonography (US), endoscopy, endoscopic US, videocapsule endoscopy, computerized tomography, magnetic resonance imaging, selective abdominal angiography, 111In-pentetreotide scintigraphy (and intraoperative radionuclide probe), 123I (131I)-metaiodobenzylguanidine (MIBG) scintigraphy, bone scintigraphy and 11C-5-HT positron emission tomography (PET). Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs, interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)-embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation of liver metastases, cryosurgery of liver metastases, occasionally liver transplantation, radiotherapy-coupled somatostatin analogs, 131I-MIBG and occasionally chemotherapy.

Manejo del tumor carcinoide del aparato digestivo y del síndrome carcinoide / Management of gastrointestinal carcinoid tumors and carcinoid syndrome

Introducción. Los tumores carcinoides son raros, la mayoría de las publicaciones informan casos clínicos aislados y la descripción de series clínicas es limitada. La calidad de vida y el tiempo de supervivencia de los pacientes dependen del control del crecimiento tumoral y de la paliación adecuada de sus síntomas. Objetivo. Informar datos epidemiológicos y formas de manejo de esta tumoración así como del síndrome carcinoide en el Instituto Nacional de Cancerología, (INCan) de México durante los últimos 15 años. Métodos. Se revisaron los expedientes clíncos de pacientes diagnosticados y tratados de tumores carcinoides en el INCan de 1982 a 1997. Resultados. El sitio primario más frecuente de localización fue el aparato digestivo (61 por ciento) seguido del árbol broncopulmonar (23 por ciento). De los del aparato digestivo, la mayoría se localiza en el colon derecho y el apéndice cecal. La supervivencia mayor fue en los de origen apendicular, menores de 2 cm y/o localizados. Al momento del diagnóstico 47 por ciento tenían enfermedad metastásica siendo también factor de mal pronóstico. En nuestro medio, el interferón solo o en combinación con octreotida o cirugía citorreductora ofrecen las mejores formas de paliación para el síndrome carcinoide. Conclusiones. Los carcinoides son raros, en general tienen un mejor comportamiento biológico que otros tumores. El tratamiento está encaminado a resecar las lesiones localizadas lo que incrementa la supervivencia o a paliar a aquellos pacientes sintomáticos cuyas lesiones no son resecables

[Management of digestive system carcinoid tumors and carcinoid syndrome]. / Manejo del tumor carcinoide del aparato digestivo y del síndrome carcinoide.

INTRODUCTION: Carcinoid tumors are rare, most of the publications are case reports and the clinical series are uncommon. The quality of life and survival time of these patients depend on the adequate control of tumor growth and good palliation of their symptoms. AIMS: The purpose of this study is to inform epidemiological data and forms of management for these tumors and the Carcinoid Syndrome at the National Institute of Cancerology (INCan) at Mexico City in the last 15 years. METHODS: A retrospective review of the clinical records of patients diagnosed and treated at the INCan with carcinoid tumors from 1982 to 1997 was performed. RESULTS: The most common origin place was the gastrointestinal tract (GI), and the majority involved the right colon and the appendix. The longest survivors were patients with tumors originated in the appendix, tumors smaller than 2 cm or localized. At the time of diagnosis 47% of patients had metastatic disease that was also a poor prognostic factor. The experience in our hospital seem to support the use of interferon alone or in combination with octreotide or debulking surgery for the palliation of carcinoid syndrome. CONCLUSIONS: Carcinoid tumors are rare, and have a slow growth and less aggressive biological nature than noncarcinoid tumors. Treatment should be focused on trying to cure the small or localized lesions or to find the best palliative method for those symptomatic advanced lesions.

Manifestaciones poco frecuentes de un síndrome carcinoide / Unfrequent manifestations of a carcinoid syndrome

Este trabajo estará destinado a mostrar las manifestaciones poco comues de un sindrome carcinoide de ciego. En este caso particular, la paciente presentó no sólo las clásicas manifestaciones del síndrome carcinoide, sino que también evidenció en el transcurso de su enfermedad otras menos frecuentes, lo que motivó su presentación. Se escriben así manifestaciones cutáneas, oftalmológicas, neurológicas, articulares. Se hará mención a las dificultades diagnósticas en este tipo de tumores así como a la demora en establecer un diagnóstico certero. Asimismo se discutirán las distintas opciones terapéuticas para estos síndromes y la evolución de este caso en particular(AU)

Manifestaciones poco frecuentes de un síndrome carcinoide / Unfrequent manifestations of a carcinoid syndrome

Este trabajo estará destinado a mostrar las manifestaciones poco comues de un sindrome carcinoide de ciego. En este caso particular, la paciente presentó no sólo las clásicas manifestaciones del síndrome carcinoide, sino que también evidenció en el transcurso de su enfermedad otras menos frecuentes, lo que motivó su presentación. Se escriben así manifestaciones cutáneas, oftalmológicas, neurológicas, articulares. Se hará mención a las dificultades diagnósticas en este tipo de tumores así como a la demora en establecer un diagnóstico certero. Asimismo se discutirán las distintas opciones terapéuticas para estos síndromes y la evolución de este caso en particular