Polyp Adenoma, Adenomatous

Squamous-cell papillomas or carcinomas, basal-cell tumours, sebaceous adenomas, keratoacanthomas Squamous-cell papillomas or carcinomas Squamous-cell papillomas Adenocarcinomas Adenomatous polyps Adenomas... 

Duodenal tumours are rare. They account for about one-third of all small bowel neoplasms, which in turn represent approximately 5%-6% of all GIT neoplasms (Kazerooni et al. 1992). Benign tumours include adenoma, adenomatous polyp, lipoma, and leiomyoma. The latter is a benign gastrointestinal stromal tumor (GIST) of smooth-muscle type. A lipoma is the only tumour that can be diagnosed by certainty on CT as a well-circumscribed, homogeneous intraluminal mass with characteristic fat density, based on negative attenuation numbers (Fig. 9.16). 

Exposed female mice had significant compound-related increases in nasal carcinomas (NTP 1982 Stinson et al. 1981). The incidences of combined alveolar/bronchiolar carcinoma and adenoma were significantly increased in the lungs of high-dose male and female mice as compared with control animals. In addition to these tumors, adenomatous polyps were present in tracheal, bronchial, and bronchiolar lumens (NTP 1982). 

The link between Cox-2 and polyps has been most extensively studied in an animal model of FAP, the adenomatous polyposis coli gene knockout mouse, which develops multiple intestinal polyps. In this model, both sulindac and a Cox-2 inhibitor are effective in producing regression of adenomas. When this knockout mouse was crossbred to a Cox-2 knockout mouse to produce a double adenomatous polyposis coli/Cox-2 knockout, the development of intestinal polyposis was markedly reduced (Oshima etal., 1996). 

The majority of the evidence against use of COX-2 selective agents and increased risk of cardiovascular events has been derived from three gastrointestinal clinical trails. In Adenoma Prevention with Celecoxib (APC) and Prevention of colorectal Sporadic Adenomatous Polyps (PreSAP) studies approximately 3000 patients with previously documented colorectal adenoma were randomized to high dose celecoxib (400 mg vs 800 mg) and placebo [150]. The objectives of these studies were to assess the efficacy (the recurrence of adenomata) and safety of celecoxib (substantial overdose) at 5 years. After mean period of 33 months, both studies were discontinued due to increase risk of cardiovascular events in the celecoxib recipients patients. 

Colon cancer is one of the main causes of cancer mortality in Western societies [150]. About 15-20% of colorectal tumors are causally determined by inheritance of genetic alterations such as the hereditary nonpolyposis colorectal cancer (HNPCC) and the syndrome familial adenomatous polyposis (FAP) [151,152]. Microsatellite instability, a characteristic of HNPCC, is caused by mutations in the genes essential for mismatch repair. The loss of mismatch repair has several consequences most crucially, the loss of proofreading and correction of small deletions and insertions. FAP is a rare autosomal dominant syndrome caused by an inherited mutation in the APC gene. The disease is characterized by the development of multiple colorectal adenomas, numbering from a few polyps to several thousands. 

Another potential use for these drugs was to prevent the formation of adenomatous polyps in patients with a history of colorectal adenomas. Rofecoxib and celecoxib were both tested in this disease. It was the results of this test that prompted Merck to withdraw their drug from the market since this study clearly established the increased risk of cardiovascular events when rofecoxib is used. The results were sufficiently strong to have the safety monitoring board reevaluate the data for a similar trial with celecoxib. On the basis of these data the study with celecoxib was also terminated. Interestingly, another study in which celecoxib was used to prevent polyp formation resulted in no increase in cardiovascular events. The only difference between the two studies was that in the latter case celecoxib was given once a day whereas in the prior study celecoxib was administered at the same dose but twice a day. How this difference in treatment schedules affected the toxic outcomes is unknown at the present time. 

Giardiello et al., in reviewing the role of suhndac with respect to adenomatous polyps in patients with FAP, showed that regression of adenomatous polyps was evident in case reports dating back to 1983 and 1989. These observations were also confirmed in randomized studies of sulindac. This evidence prompted them to study the ability of sulindac to prevent adenomas in patients with FAP who were phenotypically normal. ... 

Lynch et al. ° described an FAP patient who developed rectal carcinoma 15 months after beginning chemoprophylaxis with sulindac. There was metastatic adenocarcinoma in 6 of 20 perirectal lymph nodes. In addition to the carcinoma, her rectal mucosa contained two adenomas and multiple foci of adenomatous changes in flat mucosa. It was concluded that, while sulindac may alter the pathogenesis of FAP, those patients undergoing sulindac chemoprevention must be monitored closely by endoscopic examination. This surveillance should include an aggressive biopsy approach, since the absence of polyps does not prove the absence of malignant neoplastic changes. 

The progressive transformation of adenomatous polyps to invasive adenocarcinoma has been characterized as the adenoma carcinoma sequence (Muto 1975). However, because the prevalence of undetected cancer in an asymptomatic screening population is very low at ca.1%, colon polyp size is widely accepted as a surrogate end point for outcomes assessment in colorectal cancer screening programs. Thus, the concept of the advanced adenoma has been developed which is defined as an adenomatous polyp measuring 10 mm or greater... 

Colorectal cancer is associated with the presence and growth of adenomatous polyps in the bowel, the greatest malignant potential being associated with the larger adenomas. The adenomacarcinoma (or dysplasia-carcinoma) sequence[56] stages the development of colon... 

Papillomas are small pale lesions, single or multiple and difficult to distinguish from glycogen deposits. Adenomatous polyps are rare with the same features as adenomas elsewhere in the gastrointestinal tract. 

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