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INTRODUCTION: Patients with familial adenomatous polyposis develop colorectal cancers if left untreated. As indicated in patients with familial adenomatous polyposis, prophylactic colectomy has been recommended even in a milder colonic phenotype referred to as attenuated familial adenomatous polyposis. However, therapeutic strategies in attenuated familial adenomatous polyposis are still controversial. METHODS: We report a patient with attenuated familial adenomatous polyposis who has been treated with sulindac for five years. During the period of observation, she has been carefully followed up by chromoscopic and radiographic surveillance. Immunohistochemical study for cyclooxygenase-2 and genetic analysis in the adenomatous polyposis coli gene was also performed. RESULTS: Continuous administration of sulindac resulted in obvious regression of both colorectal adenomatous polyps and gastric fundic gland polyps, and no cancers developed during the observation period. Immunohistochemical study showed the decrease of cyclooxygenase-2–positive epithelial cells in colorectal polyps by the treatment. The genetic analysis revealed a C to A substitution at nucleotide 481 of her germline adenomatous polyposis coli gene, which resulted in a nonsense mutation at codon 161. CONCLUSIONS: Our case suggests that treatment with sulindac accompanied by intensive colonoscopic surveillance may be a choice of management for attenuated familial adenomatous polyposis.

At least 1% to 3% of all colorectal cancers (CRCs) are known to be due to mutations in one of the mismatch repair (MMR) genes responsible for hereditary nonpolyposis colorectal cancer (HNPCC, or “Lynch syndrome”).1 Although it is uncommon, the presence of HNPCC carries significant clinical managemen

PURPOSE: We describe a patient who had precancerous colonic symptoms and a positive family history of multiple occurrences of early-onset colorectal cancer in her first-degree and second-degree relatives consistent with hereditary nonpolyposis colorectal cancer. Hereditary nonpolyposis colorectal cancer diagnosis had not been made before her diagnosis of carcinoma of the cecum with liver metastasis. She died at age 20, leading to litigation. Controversies about standards of care, their malpractice implications, and pertinent legal issues are discussed. METHODS: Review of the medical and family history was made by the expert witness (HTL) with appropriate documentation of the chronology of symptoms, as derived from depositions. These documents revealed that the patient's mother had repeatedly discussed with the caregivers her concern about the family history of colon cancer and the need for appropriate surveillance. RESULTS: The patient's colonic symptoms progressed for a period of three years. Flexible sigmoidoscopy was performed by a nonphysician. The physician who ordered the procedure considered this appropriate because isolated polyps were reported in the patient's father and paternal uncle, which apparently led him to believe that the diagnosis was familial adenomatous polyposis. During litigation procedures, a pedigree was constructed and found to be consistent with hereditary nonpolyposis colorectal cancer. The case was settled in favor of the plaintiff before trial. CONCLUSION: It is essential to understand the natural history of hereditary nonpolyposis colorectal cancer, inclusive of the need for surveillance colonoscopy in patients at increased risk by virtue of their position in their family pedigree.

During its second meeting at Amsterdam in 1990, the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC) decided to carry out a pilot study on colorectal cancer surveillance in HNPCC. The objectives of the study were to ascertain in each of the participating centers the number of HNPCC families, the recommended screening procedures, the age at diagnosis of colorectal cancer (CRC), and the occurrence of interval cancers. Nine centers in seven countries including Denmark, Finland, Italy, Japan, The Netherlands, Switzerland, and the United States participated. Data were derived from a total of 165 families. With respect to screening, half of the centers advise colonoscopy as the only procedure. The interval between the consecutive examinations varies from one to three years. In the majority of the centers, screening begins at 20 to 25 years. Lifelong screening is recommended by three centers, while the rest advise discontinuation at age 60 to 75 years. The family material included 840 patients with colorectal cancer. The mean age at diagnosis was 45 years, and about 15 percent were diagnosed at age 60 or later. A total of 682 high-risk relatives are being followed. After the follow-up of 1 to 10 years in these families, only six cases of interval cancers were encountered.

We describe the clinical and pathologic features in four extended kindreds that are consistent with the hereditary flat adenoma syndrome (HFAS). This colon cancer susceptibility disorder is believed to be inherited as an autosomal dominant. The principal phenotypic marker is multiple colonic adenomas (usually less than 100), with a tendency for proximal location. The majority of these adenomas are flat or slightly raised and plaquelike, as opposed to polypoid. Colon cancers have typically developed in middle age and show no unusual histologic features. There are a variety of extracolonic manifestations, including adenomas and carcinomas of the small bowel and fundic gland polyps. The HFAS is contrasted with hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis (FAP) and shown to be distinct from both in the numbers and distribution of colonic adenomas and the typical age of cancer diagnosis. The clinical implications of these findings are discussed. Given its linkage to the FAP locus on 5q and the phenotypic parallels between HFAS and FAP, we conclude that HFAS is a variant of FAP.

Familial adenomatous polyposis coli is a heterogeneous disease with respect to genetics as well as its colonic polyposis and cancer phenotype. The authors report a family with variation in phenotypic expression of polyps ranging from isolated polyps to florid carpeting of the entire colonic mucosal surface. In addition to early-onset colonic cancer, a patient with isolated polyps had a seminoma and subsequently developed gastroesophageal cancer. His son, also with isolated colonic polyps, manifested a pararectal rhabdomyosarcoma. The significance of these variations can only be assessed fully through the study of cancer of all anatomic sites in many additional families.

We describe features of multiple cancers in a small kindred wherein a cluster of tumors affecting various anatomic sites has been observed among eight directline relatives. Three of these individuals have had two or more primary malignancies, and one woman showed a remarkable tolerance to invasive cancer, having had four histologically verified neoplasms (cancers of the ovary, endometrium, and colon, and myelogenous leukemia). The constellation of tumors occurring at an early age among relatives of the kindred supports a genetic etiology.

Ten families prone to cancer of the colon (in the absence of familial polyposis coli) have been investigated. A significantly greater frequency of carcinomas of the proximal colon was evident relative to non-familial colonic cancers (65% versus less than 35%, P less than .001). Moreover, family members with proximal colonic cancers experienced significantly enhanced survival, compared with family members with distal colonic or rectal cancers. Findings consistent with a genetic predisposition included early mean age at onset (45 years) and a high frequency (40%) of multiple primary cancers in the patients studied. The results are in accord with reported findings in 11 similar kindreds from the literature, and strongly suggest the existence of a heritable variety of colonic cancer in which the proximal colon is at particularly high risk. Extraordinary early diagnostic measures, including colonoscopy, are indicated for members of such families.