Douglas J. Robertson

A Pooled Analysis of Advanced Colorectal Neoplasia Diagnoses After Colonoscopic Polypectomy

BACKGROUND & AIMS Limited data exist regarding the actual risk of developing advanced adenomas and cancer after polypectomy or the factors that determine risk. METHODS We pooled individual data from 8 prospective studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance. RESULTS During a median follow-up period of 47.2 months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; standard error, 2.2) and those with an adenoma 20 mm in size or greater (19.3%; standard error, 1.5). Risk factor patterns were similar for advanced adenomas and invasive cancer. In multivariate analyses, older age (P < .0001 for trend) and male sex (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.19-1.65) were associated significantly with an increased risk for metachronous advanced neoplasia, as were the number and size of prior adenomas (P < .0001 for trend), the presence of villous features (OR, 1.28; 95% CI, 1.07-1.52), and proximal location (OR, 1.68; 95% CI, 1.43-1.98). High-grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics. CONCLUSIONS Occurrence of advanced colorectal neoplasia is common after polypectomy. Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas.

Incomplete Polyp Resection During Colonoscopy—Results of the Complete Adenoma Resection (CARE) Study

BACKGROUND & AIMS Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice. METHODS We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. Associations between IRR and polyp size, morphology, histology, and endoscopist were assessed by regression analysis. RESULTS Of 346 neoplastic polyps (269 patients; 84.0% men; mean age, 63.4 years) removed by 11 gastroenterologists, 10.1% were incompletely resected. IRR increased with polyp size and was significantly higher for large (10-20 mm) than small (5-9 mm) neoplastic polyps (17.3% vs 6.8%; relative risk = 2.1), and for sessile serrated adenomas/polyps than for conventional adenomas (31.0% vs 7.2%; relative risk = 3.7). The IRR for endoscopists with at least 20 polypectomies ranged from 6.5% to 22.7%; there was a 3.4-fold difference between the highest and lowest IRR after adjusting for size and sessile serrated histology. CONCLUSIONS Neoplastic polyps are often incompletely resected, and the rate of incomplete resection varies broadly among endoscopists. Incomplete resection might contribute to the development of colon cancers after colonoscopy (interval cancers). Efforts are needed to ensure complete resection, especially of larger lesions. ClinicalTrials.gov Number: NCT01224444.

Guidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer

The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3,4,5,6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.

Colorectal cancers soon after colonoscopy: a pooled multicohort analysis

Objective Some individuals are diagnosed with colorectal cancer (CRC) despite recent colonoscopy. We examined individuals under colonoscopic surveillance for colonic adenomas to assess possible reasons for diagnosing cancer after a recent colonoscopy with complete removal of any identified polyps. Design Primary data were pooled from eight large (>800 patients) North American studies in which participants with adenoma(s) had a baseline colonoscopy (with intent to remove all visualised lesions) and were followed with subsequent colonoscopy. We used an algorithm based on the time from previous colonoscopy and the presence, size and histology of adenomas detected at prior exam to assign interval cancers as likely being new, missed, incompletely resected (while previously an adenoma) or due to failed biopsy detection. Results 9167 participants (mean age 62) were included in the analyses, with a median follow-up of 47.2 months. Invasive cancer was diagnosed in 58 patients (0.6%) during follow-up (1.71 per 1000 person-years follow-up). Most cancers (78%) were early stage (I or II); however, 9 (16%) resulted in death from CRC. We classified 30 cancers (52%) as probable missed lesions, 11 (19%) as possibly related to incomplete resection of an earlier, non-invasive lesion and 14 (24%) as probable new lesions. The cancer diagnosis may have been delayed in three cases (5%) because of failed biopsy detection. Conclusions Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy.

Colorectal cancers detected after colonoscopy frequently result from missed lesions.

BACKGROUND & AIMS Colorectal cancers (CRCs) that are detected in patients who have received colonoscopies (interval cancers) arise from missed lesions, incomplete resections of adenomas, or de novo. We estimated rates of interval cancer from missed lesions. METHODS Adenoma miss rates, cancer prevalence among patients with adenoma (based on size), and rates of adenoma-to-cancer transitions were estimated from the literature. We used a model to apply these risk estimates to a hypothetical average-risk population that received screening colonoscopies. We calculated the proportion of individuals with tumors missed at the baseline colonoscopy and tumors that arose from missed adenomas during a 5-year follow-up period. Sensitivity analyses were performed to assess robustness. RESULTS We found that 0.7 per 1000 persons undergoing a screening colonoscopy had a cancer that was missed at the baseline colonoscopy and an additional 1.1 per 1000 subsequently developed cancer from a missed adenoma. Therefore, the expected rate of individuals with CRC, based on missed adenomas, was 1.8 per 1000 persons within 5 years. By using the most conservative assumptions-a low miss rate and low prevalence of cancer in adenomas-0.5 per 1000 persons would have a detectable CRC within 5 years after a screening colonoscopy. In contrast, using the highest reported miss rates and cancer prevalence, CRCs from missed lesions would occur in 3.5 per 1000 screened persons. CONCLUSIONS A significant number of patients undergoing a screening colonoscopy that did not detect cancer actually have a malignant lesion or adenoma that could progress in a short interval. Most interval cancers might reflect missed rather than new lesions. Improving adenoma detection could reduce the rate of interval cancers.

INFLAMMATORY BOWEL DISEASE IN THE ELDERLY

Approximately 15% of all patients with IBD first develop symptoms after age 65. As the number of elderly in the population continues to grow, clinicians should expect to see a greater number of elderly IBD patients. In general, the presenting features of IBD are similar to those encountered in younger patients, but the broad differential diagnosis of colitis in the elderly can make definitive diagnosis more challenging. Although most therapies for IBD have not been studied specifically in the elderly, as a general rule, medical and surgical treatment options are the same regardless of age. Osteoporosis, a condition generally associated with aging, should be managed aggressively in patients with IBD because many older persons already have a substantial baseline risk for accelerated bone loss.

The Association of Lifestyle and Dietary Factors with the Risk for Serrated Polyps of the Colorectum

Some serrated polyps of the colorectum are likely preinvasive lesions, evolving through a newly recognized serrated pathway to colorectal cancer. To assess possible risk and protective factors for serrated polyps and particularly to explore differences in risk factors between polyps in the right and left colorectum, we pooled data from three large multicenter chemoprevention trials. A serrated polyp was defined broadly as any serrated lesion (hyperplastic, sessile serrated adenoma, “traditional” serrated adenoma, mixed adenoma) diagnosed during each trials main treatment period of ∼3 to 4 years. Using generalized linear regression, we computed risk ratios and 95% confidence intervals as measures of the association between risk for serrated polyps and demographic, lifestyle, and dietary variables. Of the 2,830 subjects that completed at least one follow-up exam after randomization, 675 (23.9%) had at least one left-sided serrated polyp and 261 (9.2%) had at least one right-sided lesion. In the left colorectum, obesity, cigarette smoking, dietary fat, total energy intake, and red meat intake were associated with an increased risk for serrated polyps. In the right colon, aspirin treatment was associated with a reduced risk and family history of polyps and folate treatment were associated with an increased risk for serrated polyps. Our results suggest that several common lifestyle and dietary variables are associated with risk for serrated polyps, and some of these may differ for the right and left colorectum. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2310–7)

Survival after hepatic resection of colorectal cancer metastases: a national experience.

Most estimates of short‐ and long‐term survival after hepatic resection of colorectal cancer metastases are derived from surgical case series. For the current report, the authors used Medicare data to investigate operative mortality and long‐term survival in a national sample and examined the factors associated with survival.

A trial of calcium and Vitamin D for the prevention of colorectal adenomas

BACKGROUND Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopists recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. RESULTS Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. CONCLUSIONS Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.).

Irritable bowel syndrome: patients' attitudes, concerns and level of knowledge

Irritable bowel syndrome (IBS) is a common, chronic disorder that reduces patients’ quality‐of‐life. Although highly prevalent, little is known about patients’ understanding of this disorder.