Decompensation as initial presentation in patients with liver cirrhosis is associated with an increased risk of future decompensation and mortality.

BACKGROUND AND AIMS: The clinical course of patients with liver cirrhosis and adherence to hepatocellular carcinoma (HCC) screening guidelines are not well studied in the Netherlands. We investigated this and potential risk factors for decompensation and transplant-free survival (TFS) in a large regional cohort. METHODS: We performed a retrospective cohort study of patients with confirmed liver cirrhosis in Amsterdam, the Netherlands. Clinical parameters, decompensation events, development of HCC, and medication use were extracted from medical records. RESULTS: In total, 681 hospitalized and outpatients were included. Mortality risk was increased by: age (aHR 1.07, p < 0.01), smoking (aHR 1.83, p < 0.01), decompensated initial presentation (aHR 1.43, p = 0.04) and increased MELD (aHR 1.07, p < 0.01). PPI use tended to increase mortality risk (aHR 1.35, p = 0.05). The risk of future decompensation was increased with increased age (aHR 1.02, p < 0.01), decompensated initial presentation (aHR 1.37, p = 0.03) and alcohol misuse as etiology (aHR 1.34, p = 0.04). Adequately screened patients for HCC had a longer TFS compared to patients who were not (48 vs 22 months), p < 0.01). CONCLUSIONS: In patients with cirrhosis, decompensation at initial presentation was associated with an increased risk of future decompensation and mortality. Alcoholic cirrhosis was associated with an increased risk of future decompensation. Adequate HCC surveillance was associated with markedly better survival.

Dynamic clonal equilibrium and predetermined cancer risk in Barrett's oesophagus.

Surveillance of Barrett's oesophagus allows us to study the evolutionary dynamics of a human neoplasm over time. Here we use multicolour fluorescence in situ hybridization on brush cytology specimens, from two time points with a median interval of 37 months in 195 non-dysplastic Barrett's patients, and a third time point in a subset of 90 patients at a median interval of 36 months, to study clonal evolution at single-cell resolution. Baseline genetic diversity predicts progression and remains in a stable dynamic equilibrium over time. Clonal expansions are rare, being detected once every 36.8 patient years, and growing at an average rate of 1.58 cm(2) (95% CI: 0.09-4.06) per year, often involving the p16 locus. This suggests a lack of strong clonal selection in Barrett's and that the malignant potential of 'benign' Barrett's lesions is predetermined, with important implications for surveillance programs.

Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study.

OBJECTIVE: The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. METHODS: In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver operating characteristic curves and a leave-one-out analysis. RESULTS: A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain and aneusomy, were significantly associated with progression on univariate analysis. We defined an 'Abnormal Marker Count' that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI 2.6 to 29.8) increased HR when compared with the low-risk group, with an area under the curve of 0.76 (95% CI 0.66 to 0.86). CONCLUSIONS: A prediction model based on age, Barrett's length and the markers p16, MYC and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus.

CT colonography with limited bowel preparation: prospective assessment of patient experience and preference in comparison to optical colonoscopy with cathartic bowel preparation.

The purpose of this study was to prospectively compare participant experience and preference of limited preparation computed tomography colonography (CTC) with full-preparation colonoscopy in a consecutive series of patients at increased risk of colorectal cancer. CTC preparation comprised 180 ml diatrizoate meglumine, 80 ml barium and 30 mg bisacodyl. For the colonoscopy preparation 4 l of polyethylene glycol solution was used. Participants' experience and preference were compared using the Wilcoxon signed rank test and the chi-squared test, respectively. Associations between preference and experience parameters for the 173 participants were determined by logistic regression. Diarrhoea occurred in 94% of participants during CTC preparation. This side effect was perceived as severely or extremely burdensome by 29%. Nonetheless, the total burden was significantly lower for the CTC preparation than for colonoscopy (9% rated the CTC preparation as severely or extremely burdensome compared with 59% for colonoscopy; p < 0.001). Participants experienced significantly more pain, discomfort and total burden with the colonoscopy procedure than with CTC (p < 0.001). After 5 weeks, 69% preferred CTC, 8% were indifferent and 23% preferred colonoscopy (p < 0.001). A burdensome colonoscopy preparation and pain at colonoscopy were associated with CTC preference (p < 0.04). In conclusion, participants' experience and preference were rated in favour of CTC with limited bowel preparation compared with full-preparation colonoscopy.

Does a computer-aided detection algorithm in a second read paradigm enhance the performance of experienced computed tomography colonography readers in a population of increased risk?

We prospectively determined whether computer-aided detection (CAD) could improve the performance characteristics of computed tomography colonography (CTC) in a population of increased risk for colorectal cancer. Therefore, we included 170 consecutive patients that underwent both CTC and colonoscopy. All findings >or=6 mm were evaluated at colonoscopy by segmental unblinding. We determined per-patient sensitivity and specificity for polyps >or=6 mm and >or=10 mm without and with computer-aided detection (CAD). The McNemar test was used for comparison the results without and with CAD. Unblinded colonoscopy detected 50 patients with lesions >or=6 mm and 25 patients with lesions >or=10 mm. Sensitivity of CTC without CAD for these size categories was 80% (40/50, 95% CI: 69-81%) and 64% (16/25, 95% CI: 45-83%), respectively. CTC with CAD detected one additional patient with a lesion >or=6 mm and two with a lesion >or=10 mm, resulting in a sensitivity of 82% (41/50, 95% CI: 71-93%) (p = 0.50) and 72% (18/25, 95% CI: 54-90%) (p = 1.0), respectively. Specificity without CAD for polyps >or=6 mm and >or=10 mm was 84% (101/120, 95% CI: 78-91%) and 94% (136/145, 95% CI: 90-98%), respectively. With CAD, the specificity remained (nearly) unchanged: 83% (99/120, 95% CI: 76-89%) and 94% (136/145, 95% CI: 90-98%), respectively. Thus, although CTC with CAD detected a few more patients than CTC without CAD, it had no statistically significant positive influence on CTC performance.

Quality of Barrett's surveillance in The Netherlands: a standardized review of endoscopy and pathology reports.

OBJECTIVE: The quality of Barrett's surveillance relies on an adequate endoscopic inspection, obtaining a sufficient number of biopsy specimens, good communication of the endoscopic findings to the pathologist, and an accurate description of the histological findings by the pathologist. The aim of this study was to assess the quality of Barrett's surveillance in daily practice in The Netherlands. MATERIALS AND METHODS: A structured scoring list was developed to evaluate systematically the quality of endoscopy and pathology reports. From 15 hospitals, endoscopy reports and corresponding pathology reports were selected randomly and evaluated by two observers. In case of disagreement, the observers re-evaluated the reports in a consensus meeting. RESULTS: One hundred and fifty cases were evaluated. The adherence to current standard biopsy protocols (four quadrant biopsies every 2 cm) decreased with increasing Barrett's length: 0-5 cm: 79%; 5-10 cm: 50%; 10-15 cm: 30%. The indication for the endoscopy was mentioned in 28% of the pathology reports, in 4% the presence/absence of oesophagitis was communicated, and in 19% the location and/or aetiology of biopsies was described. The presence/absence of dysplasia was mentioned in 93% of pathology reports. CONCLUSION: Endoscopy reports and pathology reports in current practice do not include all relevant information for an adequate Barrett's surveillance. In short Barrett's oesophagus, the adherence to current standard biopsy protocols is acceptable, but in longer segments (with a higher risk for neoplastic progression) this is clearly insufficient. The communication between endoscopists and pathologist is suboptimal.

CT colonography with limited bowel preparation: performance characteristics in an increased-risk population.

PURPOSE: To prospectively evaluate the sensitivity and specificity of computed tomographic (CT) colonography with limited bowel preparation for the depiction of colonic polyps, by using colonoscopy as the reference standard. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Patients at increased risk for colorectal cancer underwent CT colonography after fecal tagging, which consisted of 80 mL of barium sulfate and 180 mL of diatrizoate meglumine. Bisacodyl was added for stool softening. A radiologist and a research fellow evaluated all data independently by using a primary two-dimensional approach. Discrepant findings for lesions 6 mm or larger in diameter were solved with consensus. Segmental unblinding was performed. Per-patient sensitivity and specificity, per-polyp sensitivity, and number of false-positive findings were found (for lesions > or = 6 mm and > or = 10 mm in diameter). Per-patient sensitivities (blinded colonoscopy vs CT colonography) were tested for significance with McNemar statistics. Interobserver variability was analyzed per segment (prevalence-adjusted bias-adjusted kappa values [kappa(p)]). RESULTS: One hundred fourteen of 168 patients (105 men, 63 women; mean age, 56 years) had polyps, with 56 polyps 6 mm or larger and 17 polyps 10 mm or larger. Per-patient sensitivities were not significantly different for CT colonography (consensus reading) and colonoscopy (P > or = .070). Sensitivity of CT colonography for patients with lesions 6 mm or larger and 10 mm or larger was 76% and 82%, respectively, and specificity of CT colonography was 79% and 97%, respectively. Blinded colonoscopy depicted 91% (lesions > or = 6 mm) and 88% (lesions > or = 10 mm) of disease in patients. Per-polyp sensitivity for CT colonography was 70% (lesions > or = 6 mm) and 82% (lesions > or = 10 mm). Number of false-positive findings was 42 (lesions > or = 6 mm) and six (lesions > or = 10 mm). kappa(p) Was 0.88 (lesions > or = 6 mm) and 0.96 (lesions > or = 10 mm). CONCLUSION: CT colonography with limited bowel preparation has a sensitivity of 82% and specificity of 97% for patients with polyps 10 mm or larger.

Feasibility study of computed tomography colonography using limited bowel preparation at normal and low-dose levels study.

The purpose was to evaluate low-dose CT colonography without cathartic cleansing in terms of image quality, polyp visualization and patient acceptance. Sixty-one patients scheduled for colonoscopy started a low-fiber diet, lactulose and amidotrizoic-acid for fecal tagging 2 days prior to the CT scan (standard dose, 5.8-8.2 mSv). The original raw data of 51 patients were modified and reconstructed at simulated 2.3 and 0.7 mSv levels. Two observers evaluated the standard dose scan regarding image quality and polyps. A third evaluated the presence of polyps at all three mSv levels in a blinded prospective way. All observers were blinded to the reference standard: colonoscopy. At three times patients were given questionnaires relating to their experiences and preference. Image quality was sufficient in all patients, but significantly lower in the cecum, sigmoid and rectum. The two observers correctly identified respectively 10/15 (67%) and 9/15 (60%) polyps > or =10 mm, with 5 and 8 false-positive lesions (standard dose scan). Dose reduction down to 0.7 mSv was not associated with significant changes in diagnostic value (polyps > or =10 mm). Eighty percent of patients preferred CT colonography and 13% preferred colonoscopy (P<0.001). CT colonography without cleansing is preferred to colonoscopy and shows sufficient image quality and moderate sensitivity, without impaired diagnostic value at dose-levels as low as 0.7 mSv.

MR colonography with limited bowel preparation compared with optical colonoscopy in patients at increased risk for colorectal cancer.

PURPOSE: To prospectively evaluate the diagnostic performance of magnetic resonance (MR) colonography by using limited bowel preparation in patients with polyps of 10 mm or larger in diameter in a population at increased risk for colorectal cancer, with optical colonoscopy as the reference standard. MATERIALS AND METHODS: The institutional review boards of all three hospitals approved the study. All patients provided written informed consent. In this multicenter study, patients undergoing colonoscopy because of a personal or family history of colorectal cancer or adenomatous polyps were included. Two blinded observers independently evaluated T1- and T2-weighted MR colonographic images obtained with limited bowel preparation (bright-lumen fecal tagging) for the presence of polyps. The limited bowel preparation consisted of a low-fiber diet, with ingestion of lactulose and an oral gadolinium-based contrast agent (with all three major meals) starting 48 hours prior to imaging. Results were verified with colonoscopic outcomes. Patient sensitivity, patient specificity, polyp sensitivity, and interobserver agreement for lesions of 10 mm or larger were calculated for both observers individually and combined. RESULTS: Two hundred patients (mean age, 58 years; 128 male patients) were included; 41 patients had coexistent symptoms. At colonoscopy, 12 patients had 22 polyps of 10 mm or larger. Per-patient sensitivity was 58% (seven of 12) for observer 1, 67% (eight of 12) for observer 2, and 75% (nine of 12) for both observers combined for polyps of 10 mm or larger. Per-patient specificity was 95% (178 of 188) for observer 1, 97% (183 of 188) for observer 2, and 93% (175 of 188) for both observers combined. Per-polyp sensitivity was 55% (12 of 22) for observer 1, 50% (11 of 22) for observer 2, and 77% (17 of 22) for both observers combined. Interobserver agreement was 93% for identification of patients with lesions of 10 mm or larger. CONCLUSION: In patients at increased risk for colorectal cancer, specificity of MR colonography by using limited bowel preparation was high, but sensitivity was modest.