Tratamento farmacológico das angiectasias gastrintestinais

 

T. Bana e Costa¹, M. Bispo¹, P. Barreiro¹, G. Couto¹, L. Matos¹

 

 

RESUMO

As angiectasias são a principal causa de hemorragia digestiva média nos doentes idosos e a sua abordagem, se bem que facilitada pelo recurso à enteroscopia por cápsula e com mono/duplo balão, continua difícil quando a endoscopia, a cirurgia e/ou a angiografia são ineficazes ou impossíveis e/ou perante a presença de lesões múltiplas. O tratamento farmacológico é uma opção válida nestas situações. Neste artigo revê-se o papel dos fármacos mais estudados e porventura mais promissores no momento, nesta indicação: a terapêutica hormonal, o octreótido e a talidomida.

Palavras-chave: Angiectasias gastrintestinais, hemorragia digestiva média, terapêutica hormonal, octreótido, talidomida.

 

SUMMARY

Angiodysplasias are the leading cause of small bowel bleeding in the elderly. Capsule endoscopy and single/double balloon enteroscopy made the diagnosis and treatment of bleeding angiodysplasias easier. Nevertheless, endoscopic treatment, surgery and angiography are impossible or unsuccessful in many instances, particularly when there are multiple intestinal angiodysplasia. In such cases, medical therapy is the only solution. The authors review the scientific evidence supporting the use of hormonal therapy, octreotide and thalidomide, the most studied and promising drugs until now in this setting.

Keywords: Gastrointestinal angiodysplasia, mid gastrointestinal bleeding, hormonal therapy, octreotide, thalidomide

 

 

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Bibliografia

 

1-Regula J. Vascular lesions of the gastrointestinal tract. Best Pract Res Clin Gastroenterol 2008; 22:313-328.

2-Raju GS, Gerson L, Das A, Lewis B; American Gastroenterological Association. American Gastroenterological Association (AGA) Institute technical review on obscure gastrointestinal bleeding. Gastroenterology 2007; 133: 1697-1717.

3-Mergener K, Ponchon T, Gralnek I, et al. Literature review and recommendations for clinical application of small-bowel capsule endoscopy, based on a panel discussion by international experts: consensus statements for small-bowel capsule endoscopy 2006/2007. Endoscopy 2007; 39:895-909.

4-Ell C, May A. Mid-gastrointestinal bleeding: capsule endoscopy and push-and-pull enteroscopy give rise to a new medical term. Endoscopy 2006; 38:73-75.

5-Pasha SF, Leighton JA, Das A, et al. Double-ballon enteroscopy and capsule endoscopy have comparable diagnostic yield in small-bowel disease: a meta-analysis. Clin Gastroenterol Hepatol 2008;6:671-676.

6-Kwan V, Bourke MJ, Williams SJ, et al. Argon plasma coagulation in the management of symptomatic gastrointestinal vascular lesions: experience in 100 consecutive patients with long term followup. Am J Gastroenterol 2006; 101:58-63.

7-Molina Infante J, Pérez Gallardo B, Fernández Bermejo M. Update on medical therapy for obscure gastrointestinal haemorrhage. Rev Esp Enferm Dig 2007; 99:457-462.

8-Madanick RD, Barkin JS. Hormonal therapy in angiodysplasia: should we completely abandon its use? Gastroenterology 2002; 123:2156; author reply 2156-7.

9-Menefee MG, Flessa HC, Glueck HI, Hogg SP. Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease). An electron microscopic study of the vascular lesions before and after therapy with hormones. Arch Otolaryngol 1975; 101:246-51.

10-Liu YK, Kosfeld RE, Marcum SG. Treatment of uraemic bleeding with conjugated oestrogen. Lancet 1984; 2:887-90.

11-Panés J, Casadevall M, Fernández M, Piqué JM, Bosch J, Casamitjana R, et al. Gastric microcirculatory changes of portal-hypertensive rats can be attenuated by long-term estrogen-progestagen treatment. Hepatology 1994; 20:1261-70.

12-Foutch PG. Angiodysplasia of the gastrointestinal tract. Am J Gastroenterol. 1993; 88:807-18.

13-Van Cutsem E, Rutgeerts P, Coremans G, Vantrappen G. Dose-response study of hormonal therapy in bleeding gastrointestinal vascular malformations (abstr). Gastroenterology 1993; 104:A286.

14-Van Cutsem E, Rutgeerts P, Vantrappen G. Treatment of bleeding gastrointestinal vascular malformations with oestrogen-progesterone. Lancet 1990; 335:953-5.

15-Junquera F, Santos J, Saperas E, Armengol JR, Malagelada JR. Estrogen and progestagen treatment in digestive hemorrhage caused by vascular malformations. Gastroenterol Hepatol 1995;18:61-5.

16-Barkin JS, Ross BS. Medical therapy for chronic gastrointestinal bleeding of obscure origin. Am J Gastroenterol 1998; 93:1250-4.

17-Tran A, Villeneuve JP, Bilodeau M, Willems B, Marleau D, Fenyves D, et al. Treatment of chronic bleeding from gastric antral vascular ectasia (GAVE) with estrogen-progesterone in cirrhotic patients: an open pilot study. Am J Gastroenterol 1999; 94:2909-11.

18-Manzanera MJ, Gutiérrez E, Domínguez-Gil B, García JA, González E, Praga M. Digestive haemorrhage due to angiodysplasia in dialysis patients. Treatment with conjugated estrogens. Nefrologia 2005; 25:412-5.

19-Lewis BS, Salomon P, Rivera-MacMurray S, Kornbluth AA, Wenger J, Waye JD. Does hormonal therapy have any benefit for bleeding angiodysplasia? J Clin Gastroenterol 1992; 15:99-103.

20-Junquera F, Feu F, Papo M, Videla S, Armengol JR, Bordas JM, et al. A multicenter, randomized, clinical trial of hormonal therapy in the prevention of rebleeding from gastrointestinal angiodysplasia. Gastroenterology. 2001; 121:1073-9.

21-Velasco FJ, Ramos A, Peixe B, Açucena F, Sousa D, Guerreiro H, et al. Resposta à hormonoterapia em doente com hemorragia por angioectasias do intestino delgado diagnosticadas por cápsula endoscópica. GE – J Port Gastrenterol 2008; 15:110-13.        [ Links ]

22-Leite S, Cotter J/ Velasco FJ. Carta ao Editor/Resposta do Autor. GE – J Port Gastrenterol 2009;16:35-36.        [ Links ]

23-Petitti DB, Wingerd J, Pellegrin F, Ramcharan S. Risk of vascular disease in women. Smoking, oral contraceptives, noncontraceptive estrogens, and other factors. JAMA 1979; 242:1150-4.

24-Buring JE. Low-dose oral contraceptives and stroke. N Engl J Med 1996; 335:53-4.

25-Scarpignato C. Octreotide: from basic science to clinical medicine. Karger Prog Basic Clin Pharmacol 1996; 10.

26-Blich M, Fruchter O, Edelstein S, Edoute Y. Somatostatin therapy ameliorates chronic and refractory gastrointestinal bleeding caused by diffuse angiodysplasia in a patient on anticoagulation therapy. Scand J Gastroenterology 2003; 38:81-3.

27-Torsoli A, Annibale B, Viscardi A. Treatment of bleeding due to diffuse angiodysplasia of the small intestine with somatostatin analogue. Eur J Gastroenterol Hepatol 1991; 3:785-7.

28-Rossini FP, Arrigoni A, Pennazio M. Ocretotide in the treatment of bleeding due to angiodysplasia of the small intestine. Am J Gastroenterol 1993; 88:1424-7.

29-Nardode G, Rocco A, Balzano T, Budillon G. The efficacy of octreotide in chronic bleeding due to vascular abnormalities of the gastrointestinal tract. Aliment Pharmacol Ther 1999; 13:1429-1436.

30-Junquera F, Saperas E, Videl S, Feu F, Vilaseca J, Armengol J, Bordas J, Pique J, Malagelada J. Long term efficacy of octreotide in the prevention of recurrent bleeding from gastrointestinal angyodysplasia. Am J Gastroenterol 2007; 102:254-260.

31-Bowers M, McNulty O, Mayne E. Ocreotide in the treatment of gastrointestinal bleeding caused by angiodysplasias in two patients with von Willebrand´s disease. Br J Hematol 2000; 108:524-7.

32-McKeage K, Cheer S, Waqstaff AJ. Octreotide long-acting release (LAR). A review of its use in the management of acromegaly. Drugs 2003; 63:2473-99.

33-Anthony LB. Long acting formulations of somatostatin analogues. Ital J Gastroenterol Hepatol 1999; 31:S216-8.

34-Scaglione G, Pietrini L, Russo F, Franco M, Sorrentini I. Long-acting octreotide as rescue therapy in chronic bleeding from gastrointestinal angiodysplasia. Aliment Pharmacol Ther 2007; 26:935-942.

35-Orsi P, Guatti-Zuliani C, Okolicsanyi L. Long-acting octreotide is effective in controlling rebleeding angiodysplasia of the gastrointestinal tract. Digest Liver Dis 2001; 33:330-4.

36-Bernstein J. Thalidomide. Clin Toxicol Rev 1999; 21.

37-Matthews S, McCoy C. Thalidomide: a review of approved and investigational uses. Clin Ther 2003;25:342-395.

38-Bauditz J, Schachschal G, Wedel S, et al. Thalidomide for treatment of severe intestinal bleeding. Gut 2004; 53:609-612.

39-Dabak V, Kuriakose P, Kamboj G, et al. A pilot study of thalidomide in recurrent GI bleeding due to angiodysplasias. Dig Dis Sci 2007; 53:1632-1635.

40-Shurafa M, Kamboj G. Thalidomide for the treatment of bleeding angiodysplasias. Am J Gastroenterol 2003; 98:221-222.

41-Heidt J, Langers A, Van Der Meer F, et al. Thalidomide as treatment for digestive tract angiodysplasias Nether J Med 2006; 64:425-428.

42-Hirri H, Green P, Lindsay J. Von Willbrand’s disease and angiodysplasia treated with thalidomide. Hemophilia 2006; 12:285-286.

43-Alberto S, Felix J. Thalidomide for the treatment of severe intestinal bleeding. Endoscopy 2008;40:788.

 

 

¹Serviço de Gastrenterologia, Centro Hospitalar de Lisboa Ocidental - Lisboa, Portugal

 

Correspondência:

Tiago Bana e Costa

Serviço de Gastrenterologia

Centro Hospitalar de Lisboa Ocidental

(Hospital de Egas Moniz)

Rua da Junqueira 126

1349-019 Lisboa

Telefone: 213 624 139

E-mail: tiagocosta@netcabo.pt

Recebido para publicação: 26/05/2009

Aceite para publicação: 09/07/2009