PURPOSE: To evaluate methods for contrast material labeling of stool in the unprepared colon for computed tomographic (CT) colonography and to determine their sensitivity for polyp detection. MATERIALS AND METHODS: Fifty-six patients with suspected or known polyps were assigned to five groups. Two to seven doses of 225 mL of dilute contrast material were orally administered during 24 or 48 hours. Transverse CT images were assessed for effectiveness of stool labeling. Colonoscopy was performed in all patients and was the standard. Two radiologists blinded to prior imaging and colonoscopic results assessed polyp detection. RESULTS: For each group, average stool labeling scores and ranges were as follows: 24 hour two dose, 16% and 8%-21%; 24 hour five dose, 53% and 27%-66%; 48 hour four dose, 38% and 22%-48%; 48 hour six dose, 68% and 54%-77%; and 48 hour seven dose, 88% and 75%-98%. Sensitivity for the two radiologists for the identification of patients with polyps 1 cm or larger for each group was as follows: 24 hour two dose, 50% and 67%; 24 hour five dose, 100% and 100%; 48 hour four dose, 58% and 75%; 48 hour six dose, 56% and 67%; and 48 hour seven dose, 100% and 80%. CONCLUSION: Ingestion of contrast material adequately labels stool for lesion identification; a 48-hour lead time and multiple doses of contrast material are required. Sensitivity for polyp detection in patients with adequate stool labeling approaches the sensitivity for polyp detection in prepared colons.

Twenty percent of colorectal cancers (CRCs) arise in people who have a family history of CRC in at least one other relative. Although a fraction of these CRCs are explained by two well-described autosomal dominant syndromes-5% by hereditary nonpolyposis colorectal cancer (HNPCC) and 1% by familial adenomatous polyposis (FAP)-the cause of the remaining 14% of familial aggregates of CRC is unknown. Many cases of HNPCC are due to germline mutations in DNA mismatch repair genes, leading to the tumor phenotype of microsatellite instability (MSI), and most cases of FAP are caused by germline APC mutations. To date, non-FAP familial CRC aggregates have not been evaluated for germline APC mutations. In this study, we examined the involvement of germline APC mutations in 79 individuals with CRC who had early-age onset of their cancer (age < 50 years) and/or a family history of CRC. Cases with FAP or HNPCC due to defective mismatch repair were excluded from the study. Using conformation-sensitive gel electrophoresis and the protein truncation test as the screening methods, no functionally significant germline mutations were detected for any of the cases. An apparently silent polymorphism resulting in a 1-bp alteration of A --> G (proline --> proline) in exon 4 was observed. Additionally, four intervening sequence (IVS) alterations were detected: IVS2-53t-->c in 3 cases; IVS4-17ins T in 3 cases; IVS5+32t-->c in 16 cases; and IVS5+33g-->a in 1 case. All appeared to be polymorphisms present in similar proportions in an average-risk population. We conclude that germline APC mutations do not account for familial MSS (stable microsatellite) CRC associated with few synchronous polyps.

BACKGROUND & AIMS: Assay of altered DNA exfoliated into stool represents an intriguing approach to screen for colorectal neoplasia, but multiple markers must be targeted because of genetic heterogeneity. We explored the feasibility of a stool assay panel of selected DNA alterations in discriminating subjects with colorectal neoplasia from those without. METHODS: Freezer-archived stools were analyzed in blinded fashion from 22 patients with colorectal cancer, 11 with adenomas > or =1 cm, and 28 with endoscopically normal colons. After isolation of human DNA from stool by sequence-specific hybrid capture, assay targets included point mutations at any of 15 sites on K-ras, p53, and APC genes; Bat-26, a microsatellite instability marker; and highly amplifiable DNA. RESULTS: Analyzable human DNA was recovered from all stools. Sensitivity was 91%(95% confidence interval, 71%-99%) for cancer and 82%(48%-98%) for adenomas > or =1 cm with a specificity of 93%(76%-99%). Excluding K-ras from the panel, sensitivities for cancer were unchanged but decreased slightly for adenomas to 73%(39%-94%), while specificity increased to 100%(88%-100%). CONCLUSIONS: Assay of altered DNA holds promise as a stool screening approach for colorectal neoplasia. Larger clinical investigations are indicated.

OBJECTIVES--To define the validity of fecal blood as a marker for colorectal neoplasia in the screening setting and to compare yields by Hemoccult and HemoQuant fecal occult blood screening tests. DESIGN--A multicenter masked comparison of fecal blood test results against structural colorectal evaluations and longitudinal follow-up, serving as criterion standards, in nonreferred subjects at risk for colorectal neoplasia. SETTING--Communities, primary care centers, referral centers. PARTICIPANTS--Two groups:(1) 1217 patients aged at least 18 years undergoing routine structural surveillance evaluations following curative resection of a colorectal tumor and (2) 12312 relatives of colorectal cancer patients aged at least 50 years. INTERVENTIONS--Blinded Hemoccult II and HemoQuant testing on three mailed-in stool samples per subject. MAIN OUTCOME MEASURE--Sensitivity of fecal blood tests for colorectal neoplasia. RESULTS--In the postresection group, surveillance evaluations revealed 46 malignant colorectal neoplasms and 402 polyps. At matched specificity, sensitivity of either test for cancer was 26%(95% confidence interval, 13% to 39%). Hemoccult was positive in 21% of intraluminal recurrences, 33% of all new primary tumors, and 29% of Dukes A or B cancers; HemoQuant was elevated in 24%, 28%, and 29%, respectively. Sensitivity for polyps 1.0 cm or larger was 13% by Hemoccult and 11% by HemoQuant. In the group of relatives, estimated sensitivity for cancer at 1 to 3 years of follow-up was 25% to 33% by Hemoccult, not significantly different from the 29% to 43% by HemoQuant. CONCLUSIONS--Based on our observations in the screening setting, fecal blood appears to be a poor marker for colorectal neoplasia. Most cancers and the vast majority of polyps will be missed. Hemoccult and HemoQuant are similarly insensitive.

PURPOSE: To assess the added benefits of prone positioning in addition to supine positioning and oral iodinated contrast medium for help in the detection of colonic polyps at computed tomographic (CT) colonography. MATERIALS AND METHODS: CT colonography was performed in prone and supine positions in 180 patients with polyps or risk factors for colonic neoplasia. Patients were randomly assigned to receive a standard bowel preparation or a standard preparation plus oral iodinated contrast medium. One radiologist interpreted supine images alone, and another analyzed supine and prone images. All patients subsequently underwent colonoscopy. RESULTS: At colonoscopy, 121 large (> or =1-cm-diameter) polyps and 142 smaller (0.5-0.9-cm) polyps were identified. Prone positioning resulted in increased sensitivity for identification of patients with large (> or =1-cm) polyps (increase from 70% to 85%, P:=.004) and of patients with polyps 0.5 cm or larger (increase from 75% to 88%, P:<.005), with no change in specificity. Use of oral contrast medium did not significantly improve polyp detection even in the subset of patients in whom colonic fluid attenuation was markedly increased. CONCLUSION: Acquisition and review of supine and prone CT colonographic images significantly improves the ability to identify patients with polyps 0.5 cm in diameter or larger. Administration of oral iodinated contrast medium does not significantly improve polyp detection.

PURPOSE: To estimate the sensitivity and specificity of computed tomographic (CT) colography in detection of colorectal polyps and to compare these findings with those at axial CT. MATERIALS AND METHODS: In 70 consecutive patients, CT colography and colonoscopy were performed. Helical axial CT images and CT colographic images (multiplanar two- and three-dimensional endoluminal images) were evaluated separately by two radiologists blinded to results from colonoscopy and other imaging studies. Findings were compared with those at colonoscopy, which was the standard. RESULTS: The sensitivity and specificity for the two observers with CT colography averaged 75% and 90% in patients with adenomas 10 mm in diameter or larger, 66% and 63% in patients with adenomas 5 mm in diameter or greater, and 45% and 80% for patients with adenomas less than 5 mm in diameter, respectively. Sensitivity and specificity with axial CT were lower than those with CT colography (58% and 74%, respectively) in patients with adenomas 10 mm in diameter or larger. CONCLUSION: Compared with axial CT, CT colography appears to have superior sensitivity and specificity in detection of clinically important colorectal adenomas. Early performance of CT colography seems promising for detection of colorectal polyps 5 mm and larger.

BACKGROUND: Some reports describe an increased risk for cancer in patients with the Peutz-Jeghers syndrome. OBJECTIVE: To characterize occurrences of cancer in a large cohort of patients with the Peutz-Jeghers syndrome. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: 34 patients with the Peutz-Jeghers syndrome identified from Mayo Clinic records from 1945 to 1996. MEASUREMENTS: Cases of cancer documented by chart review and telephone follow-up. RESULTS: 26 cases of noncutaneous cancer developed in 18 of the 34 patients: 10 cases of gastrointestinal cancer and 16 cases of extraintestinal cancer. With the use of SEER (Surveillance, Epidemiology, and End Results) data for comparison, the relative risk for cancer was 18.5 (95% CI, 8.5 to 35.2) in women with the Peutz-Jeghers syndrome and 6.2 (CI, 2.5 to 12.8) in men with the syndrome (P = 0.001). In women, the relative risk for breast and gynecologic cancer was 20.3 (CI, 7.4 to 44.2). CONCLUSIONS: The Peutz-Jeghers syndrome is associated with an increased risk for cancer. The relative risk for breast and gynecologic cancers is particularly high.

PURPOSE: To evaluate methods for contrast material labeling of stool in the unprepared colon for computed tomographic (CT) colonography and to determine their sensitivity for polyp detection. MATERIALS AND METHODS: Fifty-six patients with suspected or known polyps were assigned to five groups. Two to seven doses of 225 mL of dilute contrast material were orally administered during 24 or 48 hours. Transverse CT images were assessed for effectiveness of stool labeling. Colonoscopy was performed in all patients and was the standard. Two radiologists blinded to prior imaging and colonoscopic results assessed polyp detection. RESULTS: For each group, average stool labeling scores and ranges were as follows: 24 hour two dose, 16% and 8%-21%; 24 hour five dose, 53% and 27%-66%; 48 hour four dose, 38% and 22%-48%; 48 hour six dose, 68% and 54%-77%; and 48 hour seven dose, 88% and 75%-98%. Sensitivity for the two radiologists for the identification of patients with polyps 1 cm or larger for each group was as follows: 24 hour two dose, 50% and 67%; 24 hour five dose, 100% and 100%; 48 hour four dose, 58% and 75%; 48 hour six dose, 56% and 67%; and 48 hour seven dose, 100% and 80%. CONCLUSION: Ingestion of contrast material adequately labels stool for lesion identification; a 48-hour lead time and multiple doses of contrast material are required. Sensitivity for polyp detection in patients with adequate stool labeling approaches the sensitivity for polyp detection in prepared colons.

BACKGROUND & AIMS: Computed tomographic colography (CTC) represents a novel technique for colorectal polyp detection. A prospective study was undertaken to determine the optimal CTC scanning parameters based on an artificial colon model and to assess the feasibility of CTC to detect clinically significant colorectal polyps. METHODS: A colon model was scanned by helical computed tomography at multiple parameters. Reformatted two-dimensional and three-dimensional images were then graded for polyp detection and image quality. Subsequently, 10 patients with known colon polyps underwent CTC immediately before colonoscopy. The number of polyps detected by two radiologists using CTC were compared with colonoscopy results that served as the gold standard. RESULTS: The optimal scanning parameters in the colon model were 5-mm collimation, 5 mm/s table speed, and 1-mm reconstruction interval. Ten patients had 30 polyps (range, 0.2-2.0 cm) by colonscopy, and all polyps > or = 0.5 cm were adenomas. Polyp detection by CTC for both observers was 100%(5 of 5)> or = 1 cm, 71%(5 of 7) between 0.5 and 0.9 cm, and 11%-28%(2-5 of 18)< 0.5 cm. CONCLUSIONS: Based on this small, unblinded pilot study, CTC is feasible for colorectal polyp detection > or = 0.5 cm in diameter.

We tested HemoQuant, a quantitative assay of fecal blood based on the fluorescence of heme-derived porphyrin, in 106 healthy volunteers, 170 patients with gastrointestinal symptoms but with normal diagnostic studies, 44 patients with gastrointestinal cancer, 75 patients with benign polyps, and 374 patients with a variety of other benign gastrointestinal lesions, including ulcers and erosions. In 98 per cent of the healthy volunteers, fecal hemoglobin concentrations were less than 2 mg per gram of stool. Levels were similarly low in stools from patients with symptoms and normal studies and in patients with relatively minor benign lesions. Within these groups, levels were slightly higher in those who had ingested red meat or aspirin. The fecal hemoglobin concentration was higher in patients with gastrointestinal cancer than in any other group, and 97 per cent of those with colorectal cancer had levels above 2 mg per gram. The sensitivity of HemoQuant was significantly greater than that of the guaiac test Hemoccult, particularly when heme was degraded or stools were dry. Intestinal degradation of heme to porphyrin can be measured separately by HemoQuant, and was greater when bleeding was from proximal lesions rather than distal ones. We conclude that HemoQuant is a more sensitive measure of gastrointestinal bleeding than Hemoccult, and that its capacity to measure degraded heme may be useful in indicating the anatomic site of bleeding.

To evaluate the association of Helicobacter pylori infection with gastroduodenal ulceration and symptoms in rheumatoid arthritis patients chronically ingesting nonsteroidal anti-inflammatory drugs (NSAIDs), a population-based study was performed. Residents of Olmsted County, Minnesota, and surrounding counties, 40 years of age and over with active rheumatoid arthritis taking therapeutic dose of NSAIDs daily for 6 months or more were evaluated (n = 50). An endoscopic score from 0 to 5 was assigned and independently confirmed. Biopsies were obtained from the antrum and gastric body for the presence of H. pylori. A symptom score based on the frequency and severity of dyspeptic symptoms was calculated. Substantial mucosal injury (greater than or equal to grade 2) was observed at endoscopy in 33 patients (66%); 14 (28%) had chronic ulcers. Eleven of the community patients with rheumatoid arthritis (22%) were H. pylori positive; adjusting for age, the prevalence of H. pylori was not significantly different to that in 67 health controls (25%). One or more upper gastrointestinal symptoms were reported by 19 of the community patients (38%). Adjusting for age, community rheumatoid arthritis patients with H. pylori were not more likely to have visible mucosal damage or dyspepsia, but were significantly more likely to have histological gastritis (P less than 0.01). The results suggest that, in primarily asymptomatic persons from the community with rheumatoid arthritis taking daily NSAIDs for 6 months or more, H. pylori infection is not related to the severity of visible mucosal injury.

Iron deficiency, with or without anemia, occurs commonly in long-distance runners, but the cause is unknown. The recent development of a simple quantitative assay for fecal hemoglobin, HemoQuant , allowed us to study whether gastrointestinal bleeding occurs in runners. Blood and stool samples were collected from 24 runners before and after a race of 10 to 42.2 km and from age- and sex-matched, nonrunning controls. The mean blood hemoglobin level and hematocrit were significantly lower in runners than in controls. Serum ferritin levels were below normal in 4 runners but in no controls. Fecal hemoglobin levels increased in 20 of 24 runners (p less than 0.01) after a race. Mean fecal hemoglobin level was 1.08 mg/g (range, 0.11 to 2.36) in controls and 0.99 mg/g (0.18 to 2.41) in runners before a race, but peaked at 3.96 mg/g (0.37 to 43.20) after a race. Competitive long-distance running induces gastrointestinal blood loss and may contribute to iron deficiency.