Print version ISSN 2237-9363
J. Coloproctol. (Rio J.) vol.32 no.2 Rio de Janeiro Apr./June 2012
Eduardo Fonseca Alves FilhoI; Carlos Ramon Silveira MendesII; Marcelo Da Silva BarretoIII; Rogério Souza Medrado De AlcantaraIV
ICoordinator, Service of Coloproctology, Hospital Português da Bahia - Salvador (BA), Brazil; Full member, Sociedade Brasileira de Coloproctologia (TSBCP) - Salvador (BA), Brazil
IIService of Coloproctology, Hospital Português da Bahia - Salvador (BA), Brazil; Member of the Sociedade Brasileira de Coloproctologia (ASBCP) - Salvador (BA), Brazil
IIIService of Coloproctology, Hospital Português da Bahia - Salvador (BA), Brazil; TSBCP - Salvador (BA), Brazil
IVService of Coloproctology, Hospital Português da Bahia - Salvador (BA), Brazil; ASBCP - Salvador (BA), Brazil
Carcinoid tumors are rare. They may appear in the entire gastrointestinal and respiratory tracts, with single or multiple occurrences. Prognosis is dependent on the size and location. Symptoms may appear in carcinoid syndrome, related to active substances, especially serotonin. One important aspect associated with these tumors and usually ignored is fibrogenesis. This is a case report of a patient with carcinoid tumor of the terminal ileum, treated by laparoscopy, associated with fat and fibrosis infiltration.
Keywords: carcinoid tumor; colectomy; laparoscopy.
Tumores carcinoides são pouco frequentes, podem surgir em todo o trato gastrointestinal e respiratório, podem ser únicos ou múltiplos. O prognóstico depende do tamanho e da localização do tumor. Podem ocorrer sintomas relacionados à síndrome carcinoide, decorrente da produção de substâncias ativas, em especial serotonina. Um aspecto comumente ignorado associado a estes tumores é a estimulação da fibrogênese. Relatamos um caso de tumor carcinoide de íleo, tratado por videolaparoscopia, associado à infiltração fibroadiposa.
Palavras-chave: tumor carcinoide; colectomia; laparoscopia.
Carcinoid tumors are infrequent neuroendocrine neoplasms that may occur in the entire gastrointestinal, and outside it as well1. They may be single or multiple tumors and are associated with secretion of several active substances that can lead to many specific or nonspecific symptoms, particularly related to carcinoid syndrome. The presentation, although frequent but not always remembered, is the fibrous reaction that the tumor may cause. The purpose of this study was to report a case of carcinoid tumor of the terminal ileum, treated by videolaparoscopy, associated with fat and fibrosis infiltration of the abdominal cavity and the cecum.
A 68-year-old female patient, asymptomatic, was submitted to routine ileocolonoscopy for colorectal neoplasm screening four years ago, which showed submucosal tumor in the ileum of around 1 cm and two sessile polyps of 0.5 cm in the rectum, and polypectomy of rectal polyps (tubular adenomas) was performed. The patient remained without supervision for four years. A new ileocolonoscopy was performed (Figures 1 and 2), which showed ileocecal valve bulge and submucosal tumor of the terminal ileum of around 2 cm, involving 50% of the lumen. The abdominal computed tomography (CT) showed no anomalies and imaging and laboratorial exams showed no alterations.
Considering the future risk of obstruction, impossibility of endoscopic treatment and involvement of malignancy, the surgical intervention was the adopted therapy. At the surgical inventory, performed by laparoscopy, a high amount of fibrous adherence in the abdominal cavity was observed, with no evidence of metastases. Adhesiolysis and laparoscopic right hemicolectomy were performed, with laterolateral ileotransverse lymphadenectomy and extracorporeal mechanical anastomosis (Figure 3). The patient was discharged from the hospital on the third postoperative day.
At the pathological anatomy, a carcinoid tumor of 2 cm was observed in the ileum, limited to the muscularis propria, and 23 neoplasm-free lymph nodes, as well as lipomatosis of the ileocecal valve and fat and fibrosis infiltration of the cecal appendix. The patient was taken to the service of oncology, which did not prescribe any adjuvant treatment.
The term karzinoid tumor was first used in 1907, by Oberndorfer, to describe tumors less aggressive than adenocarcinomas2. Carcinoid tumors derive from enterochromaffin cells, which are part of the diffuse endocrine system (amine precursor uptake and decarboxylation - APUD); although usually occurring in the form of subepithelial lesions, they are histologically considered epithelial tumors3.
According to their embryological origin, carcinoid tumors can be classified as: foregut (thymus, respiratory system, stomach, duodenum, pancreas and ovaries), midgut (jejunum, ileum, appendix and proximal colon); hindgut (distal colon and rectum)2. The most frequently affected structures are: appendix, ileum, rectum and bronchi1-5.
In a clinical perspective, they can be classified as functioning or non-functioning, depending on the production of substances, such as amines (serotonin and histamine), proteins (hormones and kinins) and prostaglandins. The first type causes carcinoid syndrome associated with vasomotor symptoms: hot flashes, alterations to systemic arterial pressure, bronchospasm and diarrhea6,7. The syndrome invariably occurs associated with liver metastases or tumors outside the hepatic portal system1. Metastases are more common in tumors in the jejunum and ileum. Tumors smaller than 1 cm rarely cause metastases, while around 10% of the tumors up to 2 cm and 70% of tumors over 2 cm are associated with metastases.
Insulin-like growth factor (IGRF) and vascular endothelial growth factor (VEGF) are related to pulmonary and intestinal carcinoid tumors, and the increased expression of these factors is associated with tumor growth due to increased angiogenesis, which seems to be related to metastases and reduced survival1.
Another aspect related to the production of substances by the tumor, especially serotonin and the transforming growth factor-beta 1 (TGF-β1), is the occurrence of fibrogenesis, mainly in tumors of the ileum and jejunum, which many times leads to bowel obstruction3,4. Fibrosis usually occurs in the mesentery, called desmoplastic reaction. Fibrosis occurs less frequently in the retroperitoneum, pleura, skin and endocardium, leading to heart valve lesions, particularly in the right side.
Serotonin regulates the production of TGF-β, which, in turn, promotes the collagen synthesis by stimulating fibroblasts in the extracellular matrix. Tachykinins promote the DNA synthesis in fibroblasts and neurokinins are involved in heart valve fibrosis4,8.
Studies show that high serum levels of serotonin bound with platelets and high urinary levels of 5-hydroxy-indole-acetic acid (5-HIAA - the serotonin metabolite produced in the kidneys) are commonly associated with liver metastases; whereas the peritoneal mass associated with fibrosis is only related to high levels of serotonin bound with platelets1.
The preoperative diagnosis is not always possible. The urinary excretion of 5-HIAA above 8 mg/24 h presents sensitivity and specificity of 73% and 100%, respectively2. Hindgut and foregut tumors are not associated with high urinary levels of 5-HIAA, neither with serum serotonin, but the serum level of platelet serotonin is more sensitive in the detection of these tumors. Imaging exams are more useful when associated with methods that detect metabolites secreted by the tumor, such as: scintillography and positron emission tomography (PET). Fibrous tumors smaller than 1.5 cm are identified in tomography in 50 to 75% of midgut tumors2.
The treatment is surgical, depending on the tumor location and size. Tumors of the appendix smaller than 1 cm can be treated through appendicectomy and tumors over 2 cm, with right hemicolectomy. Tumors of intermediate size should be individualized. Small bowel tumors are treated with resections of both primary and secondary lesions. Colon tumors should be resected depending on their location. Rectal tumors smaller than 1 cm can be treated with local resections, for 1 to 2 cm, the treatment is individualized, over 2 cm, with rectosigmoidectomy, if possible, or rectal amputation6.
The drug treatment I used to relieve the symptoms related to carcinoid syndrome, such as octeocride, lanreotide, H2 blockers, phenothiazine, corticosteroids, serotonin blockers2. Chemotherapy is ineffective in advanced stages of the diseases. Substances that inhibit angiogenesis and tumor growth, such as endostatin, sunitinib, sorafenib and bevacizumab, seem to bring promising results1. Prognosis is dependent on both tumor staging and location, and tumors of the ileum and jejunum present the worst prognosis.
A high level of suspicion for carcinoid tumors should be taken into account, especially in the presence of systemic symptoms and signs of local or distant fibrosis.
1. Kidd M, Modlin IM, Shapiro MD, Camp RL, Mane SM, Usinger W, et al. CTGF, intestinal stellate cells and carcinoid fibrogenesis. World J Gastroenterol 2007;13(39):5208-16. [ Links ]
2. Druce M, Rockall A, Grossman AB.Fibrosis and carcinoid syndrome: from causation to future therapy. Nat Rev Endocrinol 2009;5(5):276-83. [ Links ]
3. Jackson LN, Chen LA, Larson SD, Silva SR, Rychahou PG, Boor PJ, et al. Development and characterization of a novel in vivo model of carcinoid syndrome. Clin Cancer Res 2009;15(8):2747-55. [ Links ]
4. Bowen KA, Silva SR, Johnson JN, Doan HQ, Jackson LN, Gulhati P, et al. An analysis of trends and growth factor receptor expression of GI carcinoid tumors. J Gastrointest Surg 2009;13(10):1773-80. [ Links ]
5. Levy AD, Rimola J, Mehrotra AK, Sobin LH. From thearchives of the AFIP: benign fibrous tumors and tumorlikelesions of the mesentery: radiologic-pathologic correlation. Radiographics2006;26(1):245-64. [ Links ]
6. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97(4):934-59. [ Links ]
7. Modlin IM, Champaneria MC, Chan AK, Kidd M. A three decade analysis of 3,911 all intestinal neuroendocrine tumors: the rapid pace of no progress. Am J Gastroenterol2007;102(7):1464-73. [ Links ]
8. Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J2004;18(7):816-27. [ Links ]
Eduardo Fonseca Alves Filho
Avenida Princesa Isabel, 914, sala 316 - Barra Avenida
CEP: 40144-900 - Salvador (BA), Brazil
Submitted on: 09/30/2010
Approved on: 11/15/2010
Financing source: none.
Conflict of interest: nothing to declare.
Study carried out at the Service of Coloproctology at the Hospital Português da Bahia - Salvador (BA), Brazil.