A risk index for advanced neoplasia on the second surveillance colonoscopy in patients with previous adenomatous polyps.

BACKGROUND: Predicting the risk of advanced colorectal neoplasia on the second surveillance colonoscopy could help tailor surveillance. OBJECTIVE: To derive and validate a risk index for advanced neoplasia on the second surveillance colonoscopy. DESIGN: Retrospective cohort. SETTING: Single-specialty practice; Veterans Affairs Medical Center. PATIENTS: A total of 965 patients with baseline adenomatous polyps, 2 surveillance colonoscopies, and no reported family history of colorectal cancer; validation cohort of 372. INTERVENTIONS: Multivariable logistic regression including demographics and previous colonoscopy results; derivation and validation of a risk index. MAIN OUTCOME MEASUREMENTS: Advanced adenoma (≥1 cm in size, villous histology, or high-grade dysplasia) on the second surveillance colonoscopy. RESULTS: Mean age was 57.8 ± 9.8 years, 62% were men, and 36% had an advanced adenoma on the index colonoscopy. Associated with advanced adenoma on the second surveillance colonoscopy were age at index colonoscopy (scored 0 for younger than 55 years of age, 1 for 55-59 years of age, 2 for 60-64 years of age, and 3 for older than 65 years of age) and previous findings (non-neoplastic, nonadvanced, advanced [scored 0, 1, and 2, respectively]) on index colonoscopy and the first surveillance colonoscopy, with scores ranging from 1 to 7. Risks of advanced adenoma on the second surveillance colonoscopy with scores of 5 or less and more than 5 were 4.8% (95% confidence interval, 3.5%-6.4%) and 14.9% (95% confidence interval, 7.4%-25.7%), respectively, comprising 93% and 7%, respectively, of the cohort. Corresponding results in the validation cohort were 5.6% and 19.2%, respectively, comprising 86.1% and 13.9%, respectively, of the cohort. LIMITATIONS: Retrospective study with potential for selection bias. CONCLUSION: This index stratifies the risk of advanced adenoma on the second surveillance colonoscopy. If validated independently, it may be useful for tailoring surveillance.

Yield of the second surveillance colonoscopy based on the results of the index and first surveillance colonoscopies.

BACKGROUND AND STUDY AIMS: The risk of advanced colorectal neoplasia (ACN) after the first surveillance colonoscopy is not well quantified. The aim of the current study was to quantify the risk of ACN on the second surveillance colonoscopy based on previous colonoscopic findings. PATIENTS AND METHODS: This was a single-site study of patients with index adenomas who underwent two surveillance colonoscopies. ACN was defined as advanced adenoma (≥ 1 cm, villous histology, or high-grade dysplasia) or as "high-risk" findings (advanced adenoma or ≥ 3 non-advanced adenoma [NAA]). RESULTS: Among 509 patients with low-risk index findings, 61 (12.0 %; 95 % confidence interval [CI], 9.3 % - 15.1 %) had high-risk findings on the first surveillance colonoscopy, 11 of whom (18.0 %; 95 %CI 9.4 % - 30.0 %) had high-risk findings on second surveillance colonoscopy compared with 39 (8.7 %; 95 %CI 6.3 % - 11.7 %) of the remaining 448 patients who had normal or low-risk findings on the first surveillance colonoscopy (relative risk [RR] = 2.07; 95 %CI 1.12 - 3.83). Among 456 patients with high-risk index findings, 91 (20.0 %; 95 %CI 16.3 % - 23.9 %) had high-risk findings on the first surveillance colonoscopy, 20 of whom (22.0 %; 95 %CI 14.0 % - 31.9 %) had high-risk findings on second surveillance colonoscopy compared with 40 (11.0 %; 95 %CI 8.0 % - 146 %) of the remaining 365 patients who had normal or low-risk findings on first surveillance colonoscopy (RR = 2.01; 95 %CI 1.04 - 3.32). Results were similar when only advanced adenomas were considered. CONCLUSIONS: Patients with high-risk findings on index and first surveillance colonoscopies require close surveillance. Those with low-risk findings on index colonoscopy and normal/non-advanced findings on the first surveillance colonoscopy have low subsequent risk of ACN. These and previous data may be useful for generating recommendations for the timing of the second surveillance colonoscopy.

Oxidative stress in chronic liver disease: relationship between peripheral and hepatic measurements.

INTRODUCTION: Oxidative stress plays an important role in the pathogenesis of many liver diseases. Investigators often measure markers of oxidative stress in peripheral veins as a reflection of hepatic oxidative stress as it is not always feasible to measure oxidative stress in liver tissue. However, it is unknown whether markers of oxidative stress measured from peripheral sites accurately reflect hepatic tissue oxidative stress. The aim of this study is to examine the relationship of oxidative stress marker among hepatic tissue, hepatic and peripheral veins and urine. METHODS: Malondialdehyde (MDA), a marker of oxidative stress was measured in hepatic vein, peripheral vein and urine samples from 26 consecutive patients undergoing transjugular liver procedures. In 19 patients undergoing liver biopsies, we measured MDA by immunohistochemical staining of paraffin-embedded liver tissue. RESULTS: Peripheral venous MDA levels showed significant correlation with hepatic venous MDA levels (r = 0.62, P = 0.02), but they did not correlate with hepatic tissue MDA content (r = 0.22, P = 0.4). Hepatic venous MDA levels did not correlate with hepatic tissue MDA content (r = -0.01, P = 0.9). Subgroup analysis of patients without portal hypertension showed a positive correlation between hepatic venous and hepatic tissue MDA levels, but this was not statistically significant (r = 0.45, P = 0.22). Urinary MDA did not correlate with MDA from any other sampling location. CONCLUSION: Oxidative stress measured from the peripheral venous samples is poorly reflective of hepatic tissue oxidative stress. Hepatic venous sampling might be suitable for assessing hepatic tissue oxidative stress in patients without portal hypertension, but a larger study is needed to examine this possibility.

Polyethylene glycol vs. sodium phosphate for bowel preparation: a treatment arm meta-analysis of randomized controlled trials.

BACKGROUND: Results of meta-analyses of randomized trials comparing PEG and NaP are inconsistent and have not included trials comparing either or both preps to less traditional ones. AIM: To perform a meta-analysis by treatment arm. METHODS: Using MEDLINE and EMBASE, we identified English-language trials published from 1990 to 2008 that included PEG and/or NaP, and aggregated them by treatment arm into: 4 liter (L) PEG; 2 L PEG; split-dose PEG; two 45 ml doses of NaP +/- adjunctive medication; and NaP tablets. We compared prep quality and the proportion completing the prep. RESULTS: Among 71 trials (patient N = 10,201), excellent prep quality was present in 34% (CI, 26-41%) for 4 L PEG alone; 39% (CI, 26-51%) for 2 L PEG; 37% (CI, 28-46%) for split-dose PEG; 42% (CI, 33-51%) for NaP solution; 44% (CI, 38-51%) for NaP with adjunctive meds; and 58% (CI, 49-67%) for NaP tablets. Patients receiving NaP were more likely to complete the prep (97% [CI, 96-98%] vs. 90% [CI, 87-92%] for 4L PEG alone); however, completion rates for 2L PEG (98%) and split dose PEG (95%) were similar to NaP. CONCLUSIONS: NaP tablets resulted in better prep quality and higher completion rates compared to other regimens. In comparisons limited by sample size, split dose PEG was not statistically different from NaP solution for completion rate or prep quality.

Drug-induced QT prolongation in cirrhotic patients with transjugular intrahepatic portosystemic shunt.

GOALS AND BACKGROUND: Nearly 40% of cytochrome P450 3A (CYP3A) activity is located in the small intestine. An earlier study has shown that cirrhotics with transjugular intrahepatic portosystemic shunts (TIPS) have diminished intestinal CYP3A activity. We hypothesized that oral CYP3A substrates known to prolong QT interval may cause further prolongation of the QT interval in cirrhotic patients with TIPS. STUDY: A total of 23 patients (9 healthy controls, 6 cirrhotics without and 8 cirrhotics with TIPS) participated in a study that tested this hypothesis using erythromycin as the probe drug. Participants with cirrhosis with and without TIPS were matched for age, sex, race, BMI and etiology of liver disease. Serial electrocardiograms were obtained at baseline, after single dose of erythromycin 500 milligrams, and after 7 days of erythromycin (500 milligrams orally twice daily). QT intervals were measured in 3 consecutive beats in 3 leads and corrected QT intervals (QTc) were obtained using various correction formulae. The maximal QTc change (ΔQTc Max) after single and multiple dose administration was the primary outcome. RESULTS: At baseline, the QTc intervals (mean±S.E) in cirrhotics with TIPS (418±6 msec) and cirrhosis (431±6 msec) were significantly higher compared with controls (388±9 msec, P=0.021). After a single dose of erythromycin, there was no significant difference among the 3 groups in ΔQTc Max (P=0.7). However, after a 7 day course, cirrhotics with TIPS developed significantly greater ΔQTc Max (179.5±67.8 msec) compared with cirrhotics (31.2±9.5 msec) and healthy controls (38.3±3.3 msec) (P=0.03). CONCLUSION: This study suggests that patients with TIPS are potentially at increased risk for abnormal QT prolongation when exposed to oral CYP 3A substrates with QT prolonging effect.

Generalizability of the nonalcoholic steatohepatitis Clinical Research Network histologic scoring system for nonalcoholic fatty liver disease.

GOALS AND BACKGROUND: The recently developed histologic scoring system for nonalcoholic fatty liver disease (NAFLD) by the nonalcoholic steatohepatitis (NASH) Clinical Research Network (CRN) is becoming increasingly popular. However, its generalizability to a community setting has not been evaluated. We conducted a study to compare a community general pathologist to an expert hepatopathologist in assessing NAFLD using the NASH CRN scoring system. STUDY: Forty-eight consecutive patients with suspected NAFLD underwent liver biopsy. Histologic features of interest such as steatosis, lobular inflammation, balloon degeneration, fibrosis, NAFLD Activity Score (NAS), and the presence of NASH were scored in a blinded fashion by the 2 pathologists on 2 separate occasions 3 months apart. RESULTS: The mean (± SD) length of the liver biopsy samples was 25 ± 5 mm. Interobserver agreement (κ) between 2 pathologists was 0.62 (0.45-0.80) for steatosis, 0.44 (0.23-0.65) for lobular inflammation, 0.25 (0.11-0.38) for ballooning, 0.40 for NAS (0.28-0.52), and 0.35 (0.19-0.52) for fibrosis. The 2 pathologists diagnosed "definite NASH" in a similar proportion of patients (56% vs. 57%), but their interobserver agreement was only 0.46 (0.24-0.67) as they both diagnosed different levels of NASH (borderline vs. definite) in different subjects. Intraobserver agreement was generally comparable for steatosis, lobular inflammation, NAS, and diagnosis of NASH, but not for fibrosis. CONCLUSIONS: Clinically important differences exist between community general pathologist and expert hepatopathologist in assessing NAFLD using the NASH CRN scoring system. More studies are needed to investigate its suitability for community-based clinical practice.