K. P. Nugent

Life expectancy after colectomy and ileorectal anastomosis for familial adenomatous polyposis

PURPOSE: Despite the introduction of screening, surveillance, and prophylactic colectomy surgery, patients with familial adenomatous polyposis (FAP) are at risk of dying from other malignancies. METHODS: In order to quantify this risk and identify the causes of mortality, a retrospective life table analysis was performed on 222 patients with familial adenomatous polyposis who had undergone a total colectomy and ileorectal anastomosis between 1948 and 1990. These FAP patients were compared with an age- and sex- matched group of the general population and a relative risk of dying was calculated. RESULTS: Of 222 patients, 53 have died. In a matched group of the general population the expected number of deaths would be 15.8. The relative risk of dying is therefore 3.35. There has been no significant improvement with time and the relative risk is greatest for female patients. CONCLUSION: The three main causes of mortality are upper gastrointestinal malignancy, desmoid disease, and perioperative complications. Further research should therefore be aimed at prevention and improved treatment of these in order to improve survival.

Solitary Juvenile Polyps: Not a Marker for Subsequent Malignancy

BACKGROUND Solitary juvenile polyps are considered benign. In contrast, juvenile polyposis is associated with malignancy and poor long-term outcome. Recent reports suggest that solitary juvenile polyps may also undergo both adenomatous and malignant change. The long-term outcome of patients with solitary juvenile polyps is unknown. Patients are treated conservatively and discharged from follow-up. The present study was designed to examine the incidence of cancer and mortality of these patients, comparing their life expectancy with that of the general population. METHODS The outcome of 82 patients with a solitary juvenile polyp between 1958 and 1982 was examined by life table analysis. Patients were traced through the Office of Population Censuses and Surveys for death and cancer registration. Patients were compared with an age- and sex-matched group of the general population. RESULTS The relative risk of dying for patients who have previously had a solitary juvenile polyp in comparison with the general population was found to be 0.66 (95% confidence interval, 0.34-1.14). There was only one case of colorectal cancer. CONCLUSIONS Patients with a solitary juvenile polyp are not at increased risk of dying of or developing colorectal cancer and do not require further follow-up or investigations.

Surveillance of duodenal polyps in familial adenomatous polyposis: progress report.

Familial adenomatous polyposis (FAP) is characterized by the presence of premalignant adenomas of the large and small bowel. Prophylactic colectomy deals with the risk for colon cancer, leaving duodenal cancer as the leading cause of death. Although most FAP patients have duodenal adenomas, only approximately 5% develop duodenal cancer. This study looks at progression of duodenal polyps with time. The outcome of endoscopic surveillance in the duodenum of 70 patients with familial adenomatous polyposis was determined. A mean of 40 months elapsed between endoscopies. Outcome was measured using video comparison and a staging system that includes histological assessment. Duodenal cancer developed in one patient, and was suspected in two others. The stage of duodenal polyposis worsened in another seven patients. When histology was ignored, comparison of video recordings in 52 patients showed a worsening in 21 (40%). In conclusion, further surveillance appears warranted so that patients at high risk for duodenal cancer might receive early treatment. Should slow progression of duodenal polyposis be shown to be associated with low risk, then most patients can be safely offered less frequent endoscopies than hitherto.

Tissue prostaglandin levels in familial adenomatous polyposis patients treated with sulindac

BACKGROUND: Recent work has demonstrated a correlation between frequency of aspirin ingestion and colorectal cancer prevention. Sulindac, another nonsteroidal anti-inflammatory drug (NSAID), has been shown to cause polyp regression and a fall in cell proliferation in patients with familial adenomatous polyposis, who are destined to develop colorectal cancer unless the colon is removed. However, the mode of action of NSAIDs in colorectal carcinogenesis prevention remains to be determined, although a prostaglandin-mediated mechanism seems likely. METHODS: Rectal or duodenal biopsies from 20 patients with familial adenomatous polyposis, who had been randomized to sulindac or placebo, were analyzed for prostaglandin (PG) E2 and E2α levels before and after treatment. RESULTS: A significant fall in prostaglandin E2 and E2α (P=0.0096; PGE2, P=0.036; PGF2α Spearmans rank correlation). CONCLUSIONS: Nonsteroidal antiinflammatory drugs may prevent colorectal cancer by their inhibition of prostaglandin synthesis. Prostaglandins may be implicated in carcinogenesis through an increase in cell proliferation, through immunosuppression, by increasing neovascularization, or via a mutagenic effect.

Caffeine phenotyping of cytochrome P4501A2, N-acetyltransferase, and xanthine oxidase in patients with familial adenomatous polyposis.

Patients with familial adenomatous polyposis (FAP) and age and sex matched controls were tested for cytochrome P4501A2 (CYP1A2), N-acetyltransferase, and xanthine oxidase activities using caffeine urinary metabolites as a discriminator. FAP patients showed significant underactivity of N-acetyltransferase (which inactivates some carcinogens) and significant overactivity of CYP1A2 (which activates some carcinogens). Xanthine oxidase activity, which can generate free radicals and cause cellular damage, was significantly increased in the FAP patients. All but one of the FAP patients had undergone colectomy. A separate group of six patients was therefore assessed before and at an average time of eight weeks after colectomy. No effect on enzyme activity was seen. The differences in enzyme activities detected in this study could produce an excess of active carcinogenic metabolites in the bile of FAP patients and contribute to the high risk for intestinal cancer in FAP.