| Familial adenomatous polyposis(FAP) is a common hereditary disease of the digestive tract. Since FAP was first known 120 years ago, knowledge about FAP as well as clinical diagnosis and treatment of the condition has been evolving gradually, from knowing it as multiple polyposis in early years to the establishment of sized familial registration centers in American and European countries today;from permanent colostomy in the past to widespread use of up-date pouches; and from finding association of FAP with apenteric lesions to the study of APC genotype-phenotype at molecular level. But in China there is no sized familial FAP registration center at present, nor are there systematic data about clinical diagnosis and treatment or related research of FAP. For this reason, we conducted a follow-up study on FAP inpatients and their family lines in an attempt to gain insight into the diagnosis and treatment of FAP, and at the same time to determine whether COX-2 gene is involved in the development and progression of colorectal cancers and explore possible mechanisms of regulating its expression. On the basis of the above study, we used COX-2 as the functional target point to observe therapeutic effects of selective COX-2 inhibitor on enteral and apenteric lesions of the FAP patients and analyze the clinical significance of selective COX-2 inhibitor in preventing and curing colorectal cancers. Part I Clinical diagnosis of FAP and registration of family treesThe hallmark clinical manifestation of FAP is growth of large numbers of adenomatous polyps in the colon during adolescence. FAP patients and their families are high risk populations of colorectal carcinoma accounting for 1% of all colorectal carcinomas. FAP is associated with various enteral manifestations including fundal adenoma, duodenal adenomatous polyps, hard fibroma, epithelial hyperplasia of fundal retinal pigment and osteoma. A correct understanding of the clinical features and significance of these enteral and apenteric changes would help diagnosis and treatment of FAP. In industrial countries such as America and European countries, there are national or local FAP familial registration centers offering screening and follow-up for families of FAP patients, which has significantly lowered the incidence of colorectal carcinoma and apenteric cancers. There has been no report describing systematic studies on FAP in China. We therefore carried out a series of studies in 22 FAP patients who were admitted in Changhai Hospital between 2001 and 2003, which included examination of enteral and apenteric lesions, investigation of family lines and postoperative follow-up observation. In addition, the clinical data of 96 FAP cases clinically diagnosed between 1985 and 2000 were analyzed retrospectively, which included clinical (enteral and apenteric manifestations, methods of diagnosis and screening, surgical modality and follow-up findings). The results and observations of this part of study showed that colorectoscopy is the most reliable means of clinical diagnosis of FAP, playing an essential role in family screening; CHRPE is a highly specific accessory means of diagnosing FAP; duodenal adenoma and hard fibroma are serious apenteric lesions of FAP, affecting prognosis of FAP patients; and there is a risk of developing recurrent adenoma and carcinoma in the residual colon after subtotal colectomy. Part II Expression of COX-2 gene in FAP and sporadic colorectal cancersIn cells of mammary animals there are two sorts of cycloxygenase (COX): COX-1 and COX-2. COX-1 is mainly expressed constituently, catalyzing synthesized prostaglandins (PGs) and participating in normal physiological processes of the kidneys, the gastrointestinal tract, platelets and other histological systems; while COX-2 is an inducible enzyme, expressed inductively under the action of stimulating factors, bacterial endotoxins, cytokines and growth factors, catalyzing synthesized PG monomer to participate in pathological molecular incidents such as regulating cell... |
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