William R. Schindler

Location of Adenomas Missed by Optical Colonoscopy

Context How often does colonoscopy miss adenomas? Contribution During a multicenter screening trial, experienced colonoscopists performed same-day optical (OC) and virtual colonoscopy (VC) on 1233 asymptomatic adults. Optical colonoscopy performed without knowledge of the VC findings missed 55 of 511 polyps; 21 of these polyps were adenomas measuring 6 mm or greater. Adenomas missed by OC were usually on the proximal side of a fold or near the anal verge. Virtual colonoscopy missed 14% of the adenomas that measured 6 mm or greater that were de-tected by OC. Implications Neither OC nor VC is a perfect test: Each misses 10% to 14% of adenomas that measure 6 mm or greater. The Editors Optical colonoscopy (OC) is widely accepted as the gold standard for detecting colorectal neoplasia (1, 2). However, even in the most experienced hands, this skilled examination is understandably not infallible. Retrospective analysis has suggested that the OC miss rate for adenomas 10 mm or greater is approximately 10% (3). More recently, prospective back-to-back or tandem colonoscopy studies have reported miss rates for 10-mm adenomas ranging from 0% to 6% (4, 5). However, in addition to evaluating relatively small populations of patients with a high prevalence of polyps, a notable weakness common to these studies was that they used OC as its own reference standard. In a large, prospective, multicenter trial that was primarily intended to evaluate the performance of virtual colonoscopy (VC) in asymptomatic adults (6), we also had a unique opportunity to evaluate the adenoma miss rate on OC by segmentally unblinding the results from same-day VC. By using a reference standard other than OC itself for comparison, we could uncover lesions that may be systematically missed on repeated colonoscopies. These data not only provide novel insight into OC miss rates but also indicate the relative blind spots where more attention could be focused. Methods Study Design The institutional review boards at all 3 participating medical centers approved the study protocol for same-day VC and OC, and all patients provided written informed consent. We recruited asymptomatic adults who were referred for colorectal cancer screening. Exclusion criteria were a positive stool guiaic test result or iron deficiency anemia within the past 6 months; rectal bleeding, hematochezia, or unintentional weight loss of more than 10 pounds within the past 12 months; OC within the past 10 years or barium enema within the past 5 years; personal history of adenomatous polyps, colorectal cancer, or inflammatory bowel disease; and family history of familial adenomatous polyposis or nonpolyposis cancer syndromes. Between May 2002 and June 2003, 1253 asymptomatic adults enrolled in the study. Eight patients were excluded because of failure to reach the cecum at OC, 6 patients were excluded because of inadequate colonic preparation, and another 6 patients were excluded because of computed tomography (CT) system failure. The final study group comprised 1233 asymptomatic adults (728 men and 505 women; mean age, 57.8 years) who successfully completed same-day VC and OC. Study participants underwent colonic preparation with oral intake of 90 mL of phospho-soda and 10 mg of bisacodyl. To opacify residual colonic fluid and stool for VC examination, patients also consumed dilute oral contrast as previously described (7). Our CT protocol and VC technique have also been detailed previously (6). To briefly summarize, we obtained supine and prone CT acquisitions on multidetector scanners after patient-controlled rectal insufflation of room air. One of 6 trained radiologists interpreted VC studies by using a commercially available CT colonography system (Viatronix V3D-Colon, version 1.2, Viatronix, Inc., Stony Brook, New York). We used the 3-dimensional endoluminal fly-through view primarily for detecting polyps and 2-dimensional images for confirmation and problem solving. We measured polyps on the 3-dimensional view and recorded them by segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, or rectum). We defined the proximal colon as including the cecum to the splenic flexure. We prospectively rated diagnostic confidence for each detected lesion on a 3-point scale (most certain, intermediate, and least certain). One of 17 experienced colonoscopists performed OC immediately after VC interpretation by using standard commercial video colonoscopes (Olympus, Inc., Melville, New York). The colonoscope was advanced to the cecum and then sequentially withdrawn into more distal segments for polyp detection. The colonoscopist measured polyps by using a calibrated linear probe, which is more accurate than either visual or biopsy forceps estimation (8). Our polyp-matching algorithm requires VC and OC agreement according to size (within a 50% margin of error) and location (within the same or adjacent segment). After the colonoscopist evaluated a given segment, a study nurse unblinded the VC results for the previous segment. For any suspected polyp seen on VC that measured 5 mm or greater but was not seen on the initial blinded OC, the colonoscopist closely reexamined that segment and could review the VC images for guidance. We sent all retrieved polyps for histologic examination. For all cases in which a colorectal neoplasm measuring 6 mm or greater was found on second-look OC, we retrospectively reviewed both the VC and OC images. We recorded polyp characteristics, such as size, morphologic characteristic (sessile, pedunculated, or flat), and location on VC. If the polyp was situated on a colonic fold on VC, we further subcategorized it as being located on the back (proximal) side, front (distal) side, or edge of the fold. We analyzed both supine and prone VC sets for all cases. The primary reason that diminutive polyps measuring 5 mm at VC were included for potential unblinding at OC was that, given the relative error in polyp measurement, such polyps found on second-look OC might, in fact, measure 6 mm or greater. This allows for more accurate assessment of the OC miss rate at the 6-mm threshold. We did not include unblinded polyps that measured 5 mm or less on both VC and OC examinations in the final analysis. All study participants completed a detailed questionnaire on their personal and family medical history. For the purposes of this study, particular attention was given to the question about previous abdominal or pelvic surgery, since adhesions could conceivably result in a more difficult colonoscopic examination. Statistical Analysis Prospective OC performance was compared against the enhanced reference standard of second-look OC after segmental unblinding of VC results. We estimated exact binomial 95% CIs for OC miss rates. We used the chi-square test to compare the frequency of previous abdominal surgery among patients with and without polyps missed at OC and also to compare the OC miss rates among the 3 medical centers. We calculated the 95% CIs by using Stata software, version 7.0 for Windows (Stata Corp., College Station, Texas), and performed the chi-square tests by using SAS software, version 8.0 for Windows (SAS Institute, Inc., Cary, North Carolina). Role of the Funding Source The funding source had no role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results The performance characteristics of VC from this prospective, multicenter screening trial, using OC as the reference standard, have been previously reported (6). Our technique of segmental unblinding also allows for a separate assessment of OC by using the blinded VC results for comparison, which is the focus of this study. We identified 1310 polyps at OC in the 1233 asymptomatic adults; 511 (39.0%) of these polyps measured 5 mm or greater (Figure 1).Of these 511 polyps, 55 (10.8%) were found only on second-look OC after segmental unblinding of VC results. Twenty-four (43.6%) of the 55 unblinded lesions were nonadenomatous, including 16 hyperplastic polyps. Of the 31 missed neoplasms, 10 adenomas that measured only 5 mm were excluded from further analysis because of their diminutive size (9). Including unblinded lesions, 554 adenomas were detected on OC in this screening sample; 210 of these measured 6 mm or greater and 51 measured 10 mm or greater. Figure 1. Polyp flowchart. In 20 patients (17 men and 3 women; mean age, 58.2 years), 21 adenomas measuring 6 mm or greater (range, 6 mm to 17 mm; mean, 8.1 mm) were found on OC only after the VC results were unblinded, which represent the lesions of primary interest for this study (Table). The corresponding adenoma miss rate on prospective OC examination was 10.0% (95% CI, 6.3% to 14.9%) (21 of 210 adenomas) at a 6-mm cutoff. The 20 patients with missed adenomas that measured 6 mm or greater represented only 1.6% of the study sample (20 of 1233 patients) but 11.9% of patients with adenomas 6 mm or greater (20 of 168 patients). At 8-mm and 10-mm thresholds, the OC adenoma miss rates by polyp were 10.5% (CI, 5.2% to 18.5%) (10 of 95 adenomas) and 11.8% (CI, 4.4% to 23.9%) (6 of 51 adenomas), respectively. The 10 patients with missed adenomas 8 mm or greater represented 12.2% (10 of 82 patients) of all patients with neoplasms of this size or greater; the 6 patients with missed adenomas 8 mm or greater represented 12.5% of all patients with neoplasms 10 mm or greater. Table. Characteristics of Neoplasms Missed at Prospective Colonoscopic Evaluation Seventeen (81.0%) of the 21 unblinded neoplasms 6 mm or greater were tubular adenomas, 3 (14.3%) were tubulovillous adenomas, and 1 (4.8%) was an adenocarcinoma. Seven (33.3%) of the 21 unblinded polyps were classified as advanced lesions (that is, size 10 mm or high-grade dysplasia, prominent villous component, or focus of malignancy). There were 15 sessile lesions, 4 pedunculated lesions, and 2 flat les

Predictive value of diminutive colonic adenoma trial: The PREDICT trial

BACKGROUND & AIMS Diminutive adenomas (1-9 mm in diameter) are frequently found during colon cancer screening with flexible sigmoidoscopy (FS). This trial assessed the predictive value of these diminutive adenomas for advanced adenomas in the proximal colon. METHODS In a multicenter, prospective cohort trial, we matched 200 patients with normal FS and 200 patients with diminutive adenomas on FS for age and gender. All patients underwent colonoscopy. The presence of advanced adenomas (adenoma >or= 10 mm in diameter, villous adenoma, adenoma with high grade dysplasia, and colon cancer) and adenomas (any size) was recorded. Before colonoscopy, patients completed questionnaires about risk factors for adenomas. RESULTS The prevalence of advanced adenomas in the proximal colon was similar in patients with diminutive adenomas and patients with normal FS (6% vs. 5.5%, respectively) (relative risk, 1.1; 95% confidence interval [CI], 0.5-2.6). Diminutive adenomas on FS did not accurately predict advanced adenomas in the proximal colon: sensitivity, 52% (95% CI, 32%-72%); specificity, 50% (95% CI, 49%-51%); positive predictive value, 6% (95% CI, 4%-8%); and negative predictive value, 95% (95% CI, 92%-97%). Male gender (odds ratio, 1.63; 95% CI, 1.01-2.61) was associated with an increased risk of proximal colon adenomas. CONCLUSIONS Diminutive adenomas on sigmoidoscopy may not accurately predict advanced adenomas in the proximal colon.

Spontaneous Peritonitis Due to Streptococcus bovis

TO THE EDITOR: Spontaneous bacterial peritonitis (SBP) is a common complication in patients with ascites. It is estimated that 8–27% of patients with cirrhosis develop this complication (1). The organisms involved in SBP are usually gastrointestinal pathogens. Escherichia coli, Streptococci, and Klebsiella account for approximately 80% of the cases, but various other organisms such as Enterococcus, Enterobacter, and Clostridium species have been known to cause SBP (1). Although different species of Streptococcus have been isolated from ascitic fluid, Streptococcus bovis has only been reported in a few cases. We report a case of spontaneous bacterial peritonitis due to this organism.