Síndrome Carcinóide Online (Carcinoid Syndrome)

¨Os tumores carcinóides são derivados das células enterocromafínicas capazes de produzir grande variedade de mediadores neuroendócrinos incluindo a serotonina. A síndrome carcinóide ocorre quando esses mediadores, que são normalmente metabolizados pelo fígado, estão presentes na circulação sistêmica. Isso se deve à ocorrência de metástases hepáticas ou tumores extra-abdominais, ou quando são tumores grandes e/ou múltiplos que produzem um nível de mediadores que ultrapassa a capacidade de metabolização hepática. A síndrome carcinóide só ocorre em menos de 10% dos pacientes com tumores carcinóides. Os tumores carcinóides são mais prevalentes na quinta ou sexta décadas de vida, acometendo mais as mulheres (55%) do que os homens. Os tumores carcinóides são classificados de acordo com o local de origem. O local de origem mais freqüente é o trato gastrointestinal (cerca de 74%) seguido do trato broncopulmonar (25%). Estima-se que cerca de 75% dos doentes com tumor carcinóide desenvolvam metástases hepáticas, independentemente do local de origem. Os tumores carcinóides do intestino delgado e dos brônquios apresentam uma evolução mais maligna do que os tumores de outros locais. Os pacientes que apresentam tumores carcinóides gastrointestinais só apresentam a síndrome carcinóide se desenolverem metástases hepáticas. Os tumores carcinóides brônquicos e outros tumores carcinóides extra-intestinais podem causar a síndrome carcinóide mesmo que não haja doença metastática. O diagnóstico clínico é baseado nos sintomas de flushing e diarréia. As principais manifestações da síndrome carcinóide também incluem sudorese, sibilos, dor abdomina e fibrose cardíaca. As manifestações cutâneas relatadas são: flushing, pelagra, quadro esclerodermiforme, telangectasias e metástases cutâneas. O flushing ocorre em quase todos os casos (90%) e geralmente é restrito às regiões de face, pescoço e tronco superior. A cardiopatia carcinóide pode ser encontrada em até 60% dos pacientes com tumores carcinóides metastáticos. Consiste em depósitos de tecido fibroso no endocárdio, nos folhetos valvares, nos átrios e nos ventrículos. A valvopatia cardíaca é a manifestação histopatológica mais freqüente, com lesão da valva tricúspide (regurgitação tricúspide) sendo encontrada em 97% dos pacientes e lesão da valva pulmonar (estenose pulmonar) sendo encontrada em 88% dos pacientes. As manifestações são as de valvopatia cardíaca direita e incluem edema periférico, ascite e hepatomegalia pulsátil. A cromogranina-A é um marcador bioquímico tumoral inespecífico de tumores carcinóides e o aumento da excreção urinária de ácido 5-hidroxiindolacético (5-HIAA), um marcador específico para a síndrome carcinóide (o exame inicial mais útil para fazer o diagnóstico de síndrome carcinóide). Estudos de localização nos tumores/síndrome carcinóide são: ultrassonografia (US) abdominal, endoscopia, US endoscópica, endoscopia com vídeo-cápsula, tomografia computadorizada, ressonância magnética, angiografia abdominal seletiva, cintilografia com ¹¹¹In-pentetreotide (e sonda radioisotópica intraoperatória), cintilografia com ¹²³I (¹³¹I) -metaiodobenzilguanidina (MIBG), cintilografia óssea e tomografia por emissão de pósitron (¹¹C-5-HT). Tratamento para tumores/síndrome carcinóide são: cirurgia, análogos de somatostatina, interferon-alfa, radioterapia, embolização arterial hepática, quimioembolização hepática, escleroterapia alcoólica de metástases hepáticas (MH), ablação por radiofreqüência de MH, criocirurgia de MH, ocasionalmente transplante hepático, radioterapia associada a análogos de somatostatina, ¹³¹I-MIBG e ocasionalmente quimioterapia. Atualmente, a remoção cirúrgica do tumor carcinóide localizado consiste na primeira escolha terapêutica, tanto com finalidade curativa como paliativa. O tratamento clínico com análogos da somatostatina, por sua vez, representou um avanço no cuidado paliativo desses doentes.¨

■ Carcinoid syndrome: update on the pathophysiology and treatment

Anezka C. Rubin de Celis Ferrari, João Glasberg, Rachel P Riechelmann

Clinics (Sao Paulo) 2018; 73(Suppl 1): e490s

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096975/
■ A case of carcinoid syndrome due to malignant metastatic carcinoid tumor with carcinoid heart disease involving four cardiac valves

Brianna J. Shinn, Laura J. Tafe, Pantila Vanichakarn

Am J Case Rep. 2018; 19: 284–288.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865407/

■ Carcinoid heart disease revealed by cyanosis with both right and left valvular involvement: a case report

Khadija Khay, Salim Arous, Tarik Bentaoune et al

J Med Case Rep. 2018; 12: 23.

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■ Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial

Marianne Pavel, David J Gross, Marta Benavent et al

Endocr Relat Cancer. 2018 Mar; 25(3): 309–322

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811631/

■ Primary carcinoid tumor of the testis: a case report and review of the literatur

R A Zahr, K Chalhoub, E Mansour et al

Case Reports in Urology 2018, Article ID 3614387, 4 pages

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■ Image gallery: flush in carcinoid syndrome

A Marchetti, A Nosbaum

British Journal of Dermatology 2018, vol 179 (1)

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■ ENETS consensus guidelines for the standards of care in neuroendocrine tumors: pre- and perioperative therapy in patients with neuroendocrine tumors

Gregory Kaltsas, Martyn Caplin, Philippa Davies et al

Neuroendocrinology. 2017 Sep; 105(3): 245–254

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■ The North American Neuroendocrine Society (NANETS) consensus guidelines for surveillance and medical management of midgut neuroendocrine tumors

Jonathan R. Strosberg, Thorvardur R. Halfdanarson, Andrew M. Bellizzi et al

Pancreas. 2017 Jul; 46(6): 707–714

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■ Primary neuroendocrine neoplasm of the esophagus – Report of 14 cases from a single institute and review of the literature

Tustumi,Francisco et al.

Arq. Gastroenterol., Mar 2017, vol.54, no.1, p.4-10

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■ Tumores neuroendocrinos de origen pulmonar: Reporte de un caso.

Caviedes M, Josefina et al

Rev. chil. enferm. respir., Mar 2017, vol.33, no.1, p.47-53

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■ Predictive factors associated with carcinoid syndrome in patients with gastrointestinal neuroendocrine tumors

Beilei Cai, Michael S Broder, Eunice Chang, Tingjian Yan, David C Metz

World J Gastroenterol. 2017 Oct 28; 23(40): 7283–7291

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■ Refractory carcinoid syndrome: a review of treatment options

Rachel P. Riechelmann, Allan A. Pereira, Juliana F. M. Rego, Frederico P. Costa

Ther Adv Med Oncol. 2017 Feb; 9(2): 127–137

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■ The frequency of carcinoid syndrome at neuroendocrine tumor diagnosis: a large population-based study using SEER-Medicare dat

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Lancet Oncol. 2017 Apr; 18(4): 525–53

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■ Liver metastasis secondary to primary mesenteric carcinoid.

J Juanmartiñena-Fernández, José Francisco et al.

Rev. esp. enferm. dig., Mar 2017, vol.109, no.3, p.211-212

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■ Diverticulitis of the appendix as debut of appendicular cystadenoma and carcinoid tumor

J Fernández-Gómez-Cruzado, Laura et al.

Rev. esp. enferm. dig., Feb 2017, vol.109, no.2, p.145-146

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■ Cardiothoracic manifestations of neuroendocrine tumorus

Ramin Mandegaran, Sarojini David, Nicholas Screaton

Br J Radiol. April 2016; 89(1060): 20150787

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■ Complications from carcinoid syndrome: review of the current evidence

J M Mota, L G Sousa, R P Riechelmann

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■ Treatment of symptomatic neuroendocrine tumor syndrome: recent advances and controversies

Tetsuhide Ito, Lingaku Lee, Robert T. Jensen

Expert Opin Pharmacother. 2016 Nov; 17(16): 2191–2205

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■ Endobronchial carcinoid and concurrent carcinoid syndrome in an adolescent female

J D Cogen, J Swanson, T Ong

Case Reports in Pediatrics 2016 (2016), Article ID 2074970, 3 pages

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■ Role of computed tomography in detection and staging of small bowel carcinoid tumors

David Bonekamp, Siva P Raman, Karen M Horton, Elliot K Fishman

World J Radiol. 2015 Sep 28; 7(9): 220–235.

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■ Challenges in the diagnosis and management of well-differentiated neuroendocrine tumors of the lung (typical and atypical carcinoid): current status and future considerations

Edward M. Wolin

Oncologist. 2015 Oct; 20(10): 1123–1131

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591949/

■ Clinical benefits of above-standard dose of octreotide LAR in patient with neuroendocrine tumor for control of carcinoid syndrome symptoms: a multicenter retrospective chart review study

Jonathan R. Strosberg, Al B. Benson, Lynn Huynh et a

Oncologist. 2014 Sep; 19(9): 930–936.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153451/

■ Síndrome carcinoide y compromiso valvular cardiaco, a propósito de 2 casos.

Paredes, Alejandro et al.

Rev. méd. Chile, Mayo 2014, vol.142, no.5, p.662-666

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■ Imaging features of carcinoid heart disease

S Bradette, K Papas, J Pressacco

Canadian Association of Radiologists Journal 2014, vol 65: 213-217

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■ Serial surveillance of carcinoid heart disease: factors associated with echocardiographic progression and mortality

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British Journal of Cancer 2014, vol 111: 1703-1709

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■ Telotristat etiprate, a novel serotonin synthesis inhibitors in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide

Matthew H. Kulke, Thomas O’Dorisio, Alexandria Phan et a

Endocr Relat Cancer. 2014 Oct; 21(5): 705–71

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■ Ileal carcinoid tumor within Crohn’s disease

Mogollón, Mónica et AL

Rev. esp. enferm. dig., Apr 2014, vol.106, no.4, p.298-299

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■ Chemotherapy and irradiation for locally advanced and metastatic pulmonary carcinoid tumors

Curtis R. Chong, Lori J. Wirth, Mizuki Nishino et al

Lung Cancer. 2014 Nov; 86(2): 241–24

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■ Duodenal carcinoid with carcinoid syndrome

Ravikiran Naalla, Kamesh Konchada, Odaiyappan Kannappan, Ramachandra Lingadakai

BMJ Case Rep. 2014; 2014: bcr201320215

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■ Carcinoid tumor of the common bile duct

Ayllón-Terán, M.ª Dolores et al.

Rev. esp. enferm. dig., Dec 2014, vol.106, no.8, p.560-561

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■ Circulating serotonin and bone density, structure and turnover in Carcinoid syndrome

Jennifer S. Walsh, John D. Newell-Price, Miguel DeBono et al

J Clin Endocrinol Metab. 2013 Jul; 98(7): 2902–290

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■ Acromegalia ectópica por carcinoide bronquial.

Rojo Álvaro, J. et al.

Anales Sis San Navarra, Dic 2013, vol.36, no.3, p.563-567

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■ Carcinoid tumor of the duodenum: a rare tumor at an unusual sitie. Case series from a single institution

Waisberg, Jaques et al.

Arq. Gastroenterol., Mar 2013, vol.50, no.1, p.3-9

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-28032013000100003&lng=en&nrm=iso

■ Tumor carcinoide e sequestro pulmonar.

Westphal, Fernando Luiz et al.

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■ Primary lung carcinoid, a rare cause of paraparesis: report of a case and review of the literatures

Aikaterini N. Visouli, Kaid Darwiche, Georgios I. Kourtoglou et al

J Thorac Dis. 2012 Nov; 4(Suppl 1): 49–55.

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■ Tumores neuroendócrinos do pulmão: principais achados radiológicos em uma série de 22 casos com confirmação anatomopatológica.

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Radiol Bras, Ago 2012, vol.45, no.4, p.191-19

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■ In patient with carcinoid syndrome undergoing valve replacement: Wil a biological valve have acceptable durability?

Nigel Mabvuure, Alex Cumberworth, Sandip Hindocha

Interact Cardiovasc Thorac Surg. 2012 Sep; 15(3): 467–471

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422934/

■ Ampullary carcinoid tumor: An atypical location

Tallón-Aguilar, Luis et al

Rev. esp. enferm. dig., June 2012, vol.104, no.6, p.335-336

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■ Diagnosis, treatment and follow-up of gastric carcinoid tumors: Analysis of 14 cases

Aguirre, Alazne et al.

Rev. esp. enferm. dig., Sept 2011, vol.103, no.9, p.493-494

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■ Carcinoide gastrointestinal: Experiencia de siete años en el Instituto Nacional del Cáncer (2000-2006).

Buchholtz F, Martín et al

Rev Chil Cir, Oct 2010, vol.62, no.5, p.480-485

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■ Long-standing malignant pancreatic carcinoid treated with octreotide.

Varas-Lorenzo, M. J.

Rev. esp. enferm. dig., Nov 2010, vol.102, no.11, p.662-666

http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1130-01082010001100009&lng=es&nrm=iso

■ Usefulness of endoscopic ultrasonography (EUS) for selecting carcinoid tumors as candidates to endoscopic resection

Varas, M. J. et al.

Rev. esp. enferm. dig., Oct 2010, vol.102, no.10, p.577-582

http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1130-01082010001000002&lng=es&nrm=iso

■ Carcinoid: the disease and its implications for anaesthesia

B Powell, A Al Mukhtar, G H Mills

Continuing Education in Anaesthesia Critical Care & Pain 2010, vol 11 (1)

https://academic.oup.com/bjaed/article/11/1/9/285683

■ Carcinoid syndrome

Habib ur Rehman

CMAJ. 2009 Jun 23; 180(13): 1329.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696530/

■ Múltiples tumores carcinoides y adenocarcinomas gástricos sincrônicos

Moya Valverde, E. et al.

Rev. esp. enferm. dig., Feb 2009, vol.101, no.2, p.147-148

http://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1130-01082009000200013&lng=es&nrm=iso

■ Tumor carcinoide primario de riñón: A propósito de un caso.

Espinosa, Rául et al.

Arch. Esp. Urol., Mar 2009, vol.62, no.2, p.147-150

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■ Carcinoid tumors

Scott N. Pinchot, Kyle Holen, Rebecca S. Sippel, Herbert Chen

Oncologist. 2008 Dec; 13(12): 1255–1269

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901509/

■ Tumor carcinoide testicular asociado a teratoma: A propósito de un caso

Martínez Ballesteros, C. et al.

Actas Urol Esp, Abr 2008, vol.32, no.4, p.458-460

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■ Síndrome carcinóide: relato de caso

Niwa, Ane Beatriz Mautari and Nico, Marcello Menta Simonsen

An. Bras. Dermatol., Dez 2008, vol.83, no.6, p.549-55

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■ Carcinoide intestinal múltiple: Análisis de un caso y revisión de la literatura.

Butte B, Jean Michel et al

Rev. méd. Chile, Oct 2006, vol.134, no.10, p.1306-1309

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■ Guidelines for the diagnosis and management of carcinoid tumours. Part 1: the gastrointestinal tract. A statement from a Canadian National Carcinoid Experte Group

J Maroun, W Kocha, L Kvols et al

Curr Oncol 2006, vol 13 (2): 67-76

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■ Carcinoid tumors

R G Roberson, W J Geiger

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■ Tumor carcinóide retal polipóide: relato de caso.

Sobral, Hernán Augusto Centurión et al.

Rev bras. colo-proctol., Set 2006, vol.26, no.3, p.328-330

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■ Carcinoid syndrome: diagnosis and medical management