Polyposis

There are few definitive data to substantiate the efficacy of LTRA therapy in refractory asthma, except for patients with aspirin-sensitive asthma. This is a fairly uncommon form of asthma that occurs generally in adults who often have no prior (i.e., childhood) history of asthma or atopy, may have nasal polyposis, and who often are dependent upon oral corticosteroids for control of their asthma. This syndrome is not specific to aspirin but is provoked by any inhibitors of the cycloxygenase-1 (COX-1) pathway. These patients have been shown to have a genetic defect that causes... 

Abbreviations LDL, low density lipoprotein TNF-a, tumor necrosis factor-a IL-6, interleukin-6 APC, adenomatous polyposis coli tumor suppressor. 

Adenomatosis Polyposis Coli (APC). Whereas Dvl is a Wnt pathway activator, GSK3, Axin and APC are all inhibitors. Axin and APC help to stabilize the activity of GSK3, keeping (3-catenin levels low and Wnt target gene transcription off in the absence of a Wnt signal (Fig. 2a). 

Bladder cancer Familial Ademomatous Polyposis (genetic pre-cancerous condition)... 

The term refers to a distinct clinical syndrome characterized by aggressive and continuous inflammatory disease of the airways with chronic eosinophilic rhinosinus-itis, asthma and often nasal polyposis [6-8]. Aspirin and other NSAIDs that inhibit COX-1 exacerbate the condition, precipitating violent asthmatics attacks. This is a hallmark of the syndrome. The prevalence of aspirin hypersensitivity in the general population ranges from 0.6 to 2.5%, but is much more frequent in adult asthmatic subjects where it reaches 10-15%, although it is often underdiagnosed. 

AIA runs a characteristic clinical course [9]. It is more frequent in women than men, and is unusual in children, beginning in adulthood, on average at the age of 30 years. Rhinorrhea and nasal congestion are usually the first symptoms, subsequently complicated by polyposis. Asthma and aspirin hypersensitivity develop 2-15 years later. Once developed, aspirin intolerance remains through life, although sporadic disappearance of intolerance has been reported. Asthma, characterized by blood and nasal eosinophilia, rims a protracted course despite avoidance of analgesics. In about half the patients, the course of asthma is severe, necessitating use of systemic corticosteroids. 

In general, treatment of the asthma underlying NSAlDs sensitivity should follow standard asthma guidelines. This type of asthma is often severe and frequently high doses of inhaled corticosteroids and daily doses of oral corticosteroids are necessary. A special treatment option is a chronic desensitization to aspirin [8]. Desensitization and aspirin maintenance is routinely used in some centers for treatment of chronic rhinusinusitis with nasal polyposis. It is the only available procedure which allows AIA patients with ischemic heart disease to use aspirin. During the state of desensitization to aspirin, not only aspirin but almost all strong NSAIDs are tolerated, so desensitization and NSAID maintenance could be used for treatment of rheumatic disease or chronic pain syndromes. 

Systemic corticosteroids, administered orally or by depot injection, are considered last-resort options when all other treatments for SAR are inadequate. Systemic steroids may be used to control rhinitis symptoms in patients with severe PAR or nasal polyposis. Data comparing oral and parenteral steroid therapy are lacking however, oral therapy is preferred due to its low cost... 

Assess the patient s symptoms to determine if selftreatment is appropriate or evaluation by a physician is necessary. Determine type of symptoms, frequency (seasonal or chronic), and precipitating triggers. Does the patient have any AR-related complications (e.g., nasal polyposis, sinusitis, or otitis media) ... 

Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC)... 

Non-steroidal anti-inflammatory agents, aspirin, and acetaminophen have been suggested for use in the prevention of different cancers, especially hereditary non-polyposis colon cancer.14 While there have been observational studies linked to a reduction of ovarian carcinoma risk, evidence is still lacking. Potential... 

Adenomatous polyposis coli (APC) gene A tumor suppressor gene, acting as a gatekeeper to prevent development of tumors. A familial cancer syndrome called FAP, or familial adenomatous polyposis, is caused by mutations in APC. Mutation of APC also occurs commonly in sporadic cases of colorectal carcinoma. 

Familial adenomatous polyposis An inherited condition in which numerous polyps form, mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs 100% of the time when not treated. 

Nasal polyposis Presence of several polyps (benign growths) in the... 

Jorde LB, Watkins WS, Carlson M, Groden J, Albertsen H, Thliveris A, et al. Hnkage disequilibrium predicts physical distance in the adenomatous polyposis coli region. Am J Hum Genet 1994 54 884-898. 

Minowa T et al. Proteomic analysis of the small intestine and colon epithelia of adenomatous polyposis coli gene-mutant mice by two-dimensional gel electrophoresis. Electrophoresis 2000 21 1782—1786. 

Primary prevention is aimed at preventing colorectal cancer in an at-risk population. To date, the only strategy shown to reduce the risk is chemoprevention with celecoxib in people with familial adenomatous polyposis. 

Secondary prevention is aimed at preventing malignancy in a population that has already manifested an initial disease process. Secondary prevention includes procedures ranging from colonoscopic removal of precan-cerous polyps detected during screening colonoscopy to total colectomy for high-risk individuals (e.g., familial adenomatous polyposis). 

Tonelli F, Ficari F, Valanzano R, Brandi ML (2003) Treatment of desmoids and mesenteric fibromatosis in familial adenomatous polyposis with raloxifene. Tumore 89 391-396... 

Without regard to therapy, potentially valuable diagnostic tests are available for presymptomatic evaluation of risk of breast cancer due to predisposition from BRCA 1 or BRCA 2 and of colon cancer related to familial adenomatous polyposis (APC gene) or hereditary nonpolyposis mismatch repair genes (MSH 2). Genetic predisposition to Alzheimer disease associated with ApoE4 is neither sufficient nor necessary to lead to the clinical condition, and no definitive therapy is available. 

Celecoxib (Celebrex ) Cox 2 inhibitor Decrease in polyps in patients with familial polyposis Phase III... 

Liu, J., et al., Siah-1 mediates a novel beta-catenin degradation pathway linking p53 to the adenomatous polyposis coli protein. Mol Cell, 2001, 7f5 , 927-36. 

Individuals at risk for developing a genetic disease with a delayed age of onset may wish to learn whether they have inherited a disease-causing mutation (e.g., Huntington disease, femilial breast cancer, hemochromatosis, adenomatous polyposis coli). In some cases, presymptomatic diagnosis can be highly usefiil in preventing serious disease consequences before they occur (e.g., phlebotomy for hemochromatosis, early tumor detection for familial breast cancer). 

There is a disease termed hereditary polyposis. Victims develop a very large number of polyps in their colons, sometimes several thousand. Since the development of a colon polyp is the first step on the road to colon carcinoma, they are at high risk of colon cancer. The associated mutation is in a gene known as the APC gene. 

A second example of inherited predisposition to cancer is provided by hereditary retinoblastoma. This is a rare tumor of the retina and, when it develops, it generally develops in one eye only. Nonetheless, in children with hereditary retinoblastoma, the cancer develops early in life and generally in both eyes. This is a striking example of the inherited predisposition to develop a tumor. As in the case of hereditary polyposis, the defect is in a tumor suppressor gene, in this case RBI. Here too patients have just one intact gene in each of their cells and a single mutation in that gene may be aU that is required to initiate tumor development. 

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