An unusually severe phenotype for familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is a dominantly inherited predisposition to the development of many hundreds to thousands of adenomatous polyps of the colon. The mean age of onset is around 15 years, symptoms may arise in the third decade, and the median age for the development of colonic cancer is 35-40 years. Prophylactic colectomy reduces the risk of death from colorectal cancer to such an extent that late sequelae such as upper gastrointestinal tumours have become the main cause of mortality in appropriately managed patients. The age at which colonic surveillance begins reflects the natural history of the disease. Onset of polyp formation and cancer in childhood is very unusual, but has recently been associated with a specific mutation at codon 1309 in exon 15 where a more severe phenotype is sometimes observed. The case histories of two families are reported in which there is childhood onset of polyps in the youngest generation and in one case a carcinoma, in whom mutations have been identified in exon 11 of the APC gene. Several other affected relatives were diagnosed at ages ranging from 5-48 years, some already with a cancer at the time of first screening. Since the aim of screening for colonic polyps is prevention of colonic cancer, family members at risk should be offered genetic assessment and direct mutation testing where this is possible, usually in the early teens. In the absence of a genetic test (the situation in about one third of families) or in a known gene carrier, annual colonoscopy examination is advised from the same age. Clinicians should take note of the family history and be prepared to consider much earlier intervention if symptoms occur in a child with a family history of FAP. Where childhood onset of polyps has occurred, other children at risk in the family must be offered earlier genetic testing and endoscopic surveillance.

     

Management of colorectal cancers

The management of colorectal cancers, published in a recent issue of Effective Health Care, is reviewed.     

Results of extrafascial excision and conventional surgery for rectal cancer at Auckland Hospital

BACKGROUND: Recent studies have suggested that local recurrence rates following rectal cancer surgery are reduced if the mesorectum is removed intact within its fascia propria. The present study aims to compare the outcomes of conventional surgery for rectal cancer and surgery in which the rectum and mesorectum are removed by the technique of extrafascial excision (EFE). METHODS: All patients undergoing surgery for rectal cancer at Auckland Hospital from 1980 to 1996 were identified. Demographic, tumour, operation, outcome, survival and follow-up data were obtained from patient charts, New Zealand (NZ) Death Registry, death certificates and the NZ Electoral Roll. Complication rates, recurrence rates, overall and cancer-free survival and treatment costs were calculated for each group. RESULTS: A total of 262 patients had curative surgery (138 had conventional surgery, 124 had EFE). The groups were similar with respect to age, sex, operation performed and Dukes' stage. There was no difference in complication rates between the groups. Mean follow-up was 7 years in survivors. Twenty-nine conventional-surgery (21%) and eight EFE (6%) patients developed local pelvic recurrence. The 5-year actuarial local recurrence rates were 30% and 10%, respectively (P = 0.0006). The 5-year overall survival was 54% for conventional surgery and 60% for EFE (P = 0.23). The 5-year cancer-free survival was 63% for conventional surgery and 74% for EFE (P = 0.02). Average initial costs were NZ$15,717 and NZ$15,158 for conventional surgery and EFE, respectively. The average cost of local recurrence was an additional NZ$10,471. CONCLUSIONS: The present study adds further support to the growing evidence that excision of the mesorectum within an intact fascial envelope reduces local recurrence rates after surgery for rectal cancer. There appears to be an associated improvement in cancer-free survival. Complication rates and cost were not increased in the patients having EFE.     

Analyzing patterns of staining in immunohistochemical studies: application to a study of prostate cancer recurrence.

BACKGROUND: Immunohistochemical studies use antibodies to stain tissues with the goal of quantifying protein expression. However, protein expression is often heterogeneous resulting in variable degrees and patterns of staining. This problem is particularly acute in prostate cancer, where tumors are infiltrative and heterogeneous in nature. In this article, we introduce analytic approaches that explicitly consider both the frequency and intensity of tissue staining. METHODS: Compositional data analysis is a technique used to analyze vectors of unit-sum proportions, such as those obtained from soil sample studies or species abundance surveys. We summarized specimen staining patterns by the proportion of cells staining at mild, moderate, and intense levels and used compositional data analysis to summarize and compare the resulting staining profiles. RESULTS: In a study of Syndecan-1 staining patterns among 44 localized prostate cancer cases with Gleason score 7 disease, compositional data analysis did not detect a statistically significant difference between the staining patterns in recurrent (n = 22) versus nonrecurrent (n = 22) patients. Results indicated only modest increases in the proportion of cells staining at a moderate intensity in the recurrent group. In contrast, an analysis that compared quantitative scores across groups indicated a (borderline) significant increase in staining in the recurrent group (P = 0.05, t test). CONCLUSIONS: Compositional data analysis offers a novel analytic approach for immunohistochemical studies, providing greater insight into differences in staining patterns between groups, but possibly lower statistical power than existing, score-based methods. When appropriate, we recommend conducting a compositional data analysis in addition to a standard score-based analysis.