Jaroslaw Regula

Quality Indicators for Colonoscopy and the Risk of Interval Cancer

BACKGROUND Although rates of detection of adenomatous lesions (tumors or polyps) and cecal intubation are recommended for use as quality indicators for screening colonoscopy, these measurements have not been validated, and their importance remains uncertain. METHODS We used a multivariate Cox proportional-hazards regression model to evaluate the influence of quality indicators for colonoscopy on the risk of interval cancer. Data were collected from 186 endoscopists who were involved in a colonoscopy-based colorectal-cancer screening program involving 45,026 subjects. Interval cancer was defined as colorectal adenocarcinoma that was diagnosed between the time of screening colonoscopy and the scheduled time of surveillance colonoscopy. We derived data on quality indicators for colonoscopy from the screening programs database and data on interval cancers from cancer registries. The primary aim of the study was to assess the association between quality indicators for colonoscopy and the risk of interval cancer. RESULTS A total of 42 interval colorectal cancers were identified during a period of 188,788 person-years. The endoscopists rate of detection of adenomas was significantly associated with the risk of interval colorectal cancer (P=0.008), whereas the rate of cecal intubation was not significantly associated with this risk (P=0.50). The hazard ratios for adenoma detection rates of less than 11.0%, 11.0 to 14.9%, and 15.0 to 19.9%, as compared with a rate of 20.0% or higher, were 10.94 (95% confidence interval [CI], 1.37 to 87.01), 10.75 (95% CI, 1.36 to 85.06), and 12.50 (95% CI, 1.51 to 103.43), respectively (P=0.02 for all comparisons). CONCLUSIONS The adenoma detection rate is an independent predictor of the risk of interval colorectal cancer after screening colonoscopy.

Consensus Statements for Management of Barrett's Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barretts esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies.

Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal Endoscopy (ESGE) Guideline

MAIN RECOMMENDATIONS The following recommendations for post-polypectomy endoscopic surveillance should be applied only after a high quality baseline colonoscopy with complete removal of all detected neoplastic lesions.1 In the low risk group (patients with 1 - 2 tubular adenomas < 10 mm with low grade dysplasia), the ESGE recommends participation in existing national screening programmes 10 years after the index colonoscopy. If no screening programme is available, repetition of colonoscopy 10 years after the index colonoscopy is recommended (strong recommendation, moderate quality evidence). 2 In the high risk group (patients with adenomas with villous histology or high grade dysplasia or ≥10 mm in size, or ≥ 3 adenomas), the ESGE recommends surveillance colonoscopy 3 years after the index colonoscopy (strong recommendation, moderate quality evidence). Patients with 10 or more adenomas should be referred for genetic counselling (strong recommendation, moderate quality evidence). 3 In the high risk group, if no high risk adenomas are detected at the first surveillance examination, the ESGE suggests a 5-year interval before a second surveillance colonoscopy (weak recommendation, low quality evidence). If high risk adenomas are detected at first or subsequent surveillance examinations, a 3-year repetition of surveillance colonoscopy is recommended (strong recommendation, low quality evidence).4 The ESGE recommends that patients with serrated polyps < 10 mm in size with no dysplasia should be classified as low risk (weak recommendation, low quality evidence). The ESGE suggests that patients with large serrated polyps (≥ 10 mm) or those with dysplasia should be classified as high risk (weak recommendation, low quality evidence).5 The ESGE recommends that the endoscopist is responsible for providing a written recommendation for the post-polypectomy surveillance schedule (strong recommendation, low quality evidence).

A Placebo-controlled trial of obeticholic acid in primary biliary cholangitis

BACKGROUND Primary biliary cholangitis (formerly called primary biliary cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. Alkaline phosphatase and bilirubin levels correlate with the risk of liver transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has shown potential benefit in patients with this disease. METHODS In this 12-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 217 patients who had an inadequate response to ursodiol or who found the side effects of ursodiol unacceptable to receive obeticholic acid at a dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with adjustment to 10 mg if applicable (the 5-10-mg group), or placebo. The primary end point was an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from baseline, and a normal total bilirubin level. RESULTS Of 216 patients who underwent randomization and received at least one dose of obeticholic acid or placebo, 93% received ursodiol as background therapy. The primary end point occurred in more patients in the 5-10-mg group (46%) and the 10-mg group (47%) than in the placebo group (10%; P<0.001 for both comparisons). Patients in the 5-10-mg group and those in the 10-mg group had greater decreases than those in the placebo group in the alkaline phosphatase level (least-squares mean, -113 and -130 U per liter, respectively, vs. -14 U per liter; P<0.001 for both comparisons) and total bilirubin level (-0.02 and -0.05 mg per deciliter [-0.3 and -0.9 μmol per liter], respectively, vs. 0.12 mg per deciliter [2.0 μmol per liter]; P<0.001 for both comparisons). Changes in noninvasive measures of liver fibrosis did not differ significantly between either treatment group and the placebo group at 12 months. Pruritus was more common with obeticholic acid than with placebo (56% of patients in the 5-10-mg group and 68% of those in the 10-mg group vs. 38% in the placebo group). The rate of serious adverse events was 16% in the 5-10-mg group, 11% in the 10-mg group, and 4% in the placebo group. CONCLUSIONS Obeticholic acid administered with ursodiol or as monotherapy for 12 months in patients with primary biliary cholangitis resulted in decreases from baseline in alkaline phosphatase and total bilirubin levels that differed significantly from the changes observed with placebo. There were more serious adverse events with obeticholic acid. (Funded by Intercept Pharmaceuticals; POISE ClinicalTrials.gov number, NCT01473524; Current Controlled Trials number, ISRCTN89514817.).

Delayed-Release Oral Mesalamine 4.8 g/day (800-mg Tablet) Is Effective for Patients With Moderately Active Ulcerative Colitis

BACKGROUND AND AIMS It is not clear what induction dose of mesalamine is optimal for treating patients with mildly and moderately active ulcerative colitis (UC). This study was conducted to determine the efficacy and safety of mesalamine 4.8 g/day compared with 2.4 g/day for the treatment of moderately active UC. METHODS A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8 g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason, Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals, Inc) in 772 patients with moderately active UC. The primary endpoint was treatment success (overall improvement) at week 6, defined as improvement in the Physicians Global Assessment (based on clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy), with no worsening in any individual clinical assessment. RESULTS The primary objective of noninferiority was met. Seventy percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% (251 of 383) of patients receiving 2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9). In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical remission at week 6 compared with 35% of patients who received 2.4 g/day (P = .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients previously treated with corticosteroids, oral mesalamines, rectal therapies, or multiple UC medications. Both regimens were well-tolerated with similar adverse events. CONCLUSIONS Delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC.

The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer.

BACKGROUND AND STUDY AIM While colonoscopy screening is widely used in several European countries and the United States, there are no randomized trials to quantify its benefits. The Nordic-European Initiative on Colorectal Cancer (NordICC) is a multinational, randomized controlled trial aiming at investigating the effect of colonoscopy screening on colorectal cancer (CRC) incidence and mortality. This paper describes the rationale and design of the NordICC trial. STUDY DESIGN Men and women aged 55 to 64 years are drawn from the population registries in the participating countries and randomly assigned to either once-only colonoscopy screening with removal of all detected lesions, or no screening (standard of care in the trial regions). All individuals are followed for 15 years after inclusion using dedicated national registries. The primary end points of the trial are cumulative CRC-specific death and CRC incidence during 15 years of follow-up. POWER ANALYSIS: We hypothesize a 50 % CRC mortality-reducing efficacy of the colonoscopy intervention and predict 50 % compliance, yielding a 25 % mortality reduction among those invited to screening. For 90 % power and a two-sided alpha level of 0.05, using a 2:1 randomization, 45 600 individuals will be randomized to control, and 22 800 individuals to the colonoscopy group. Interim analyses of the effect of colonoscopy on CRC incidence and mortality will be performed at 10-year follow-up. CONCLUSIONS The aim of the NordICC trial is to quantify the effectiveness of population-based colonoscopy screening. This will allow development of evidence-based guidelines for CRC screening in the general population.

Vascular lesions of the gastrointestinal tract.

Classification of vascular abnormalities of the gastrointestinal tract on the basis of anatomy and pathophysiology has recently been suggested. Angiodysplasia, an example of an arteriovenous lesion, may cause either acute or chronic bleeding. Diagnosis may be difficult. High-quality standard endoscopy, capsule endoscopy, and double-balloon enteroscopy are most efficacious. Therapy using argon plasma coagulation is currently preferred. Pharmacological therapy has been employed, but a final conclusion about its efficacy cannot yet be drawn. Dieulafoy lesion, an arterial type of vascular abnormality, is rare but serious. It can be responsible for severe haemorrhage. Mechanical endoscopic methods are the most efficacious. Gastric antral vascular ectasia (GAVE), a capillary lesion, can be safely biopsied; it coincides with several diseases (including liver cirrhosis), may cause chronic iron-deficiency anaemia, and is best treated by argon plasma coagulation. Haemangiomas, benign neoplastic lesions, usually occur as part of other specific syndromes; they are difficult to manage due to the multiplicity and size of the lesions.

Diagnostic yield and safety of endoscopic-ultrasound guided trucut biopsy in patients with gastric submucosal tumors: a prospective study

BACKGROUND AND STUDY AIMS Endoscopic-ultrasound-guided trucut needle biopsy (EUS-TCB) has not been adequately evaluated in patients with submucosal tumors (SMTs). PATIENTS AND METHODS This prospective, uncontrolled study involving 49 consecutive patients with hypoechoic gastric SMTs (> or = 20 mm) evaluated diagnostic yield and 30-day morbidity of EUS-TCB, factors related to the success of EUS-TCB, and agreement between EUS-TCB and the surgical pathology diagnosis. Seventy-three percent of tumors were gastrointestinal stromal tumors (GIST). RESULTS Tumor tissue adequate for diagnosis was obtained by EUS-TCB in 31 patients (63 %; 95 %CI 49 % to 75 %). In the remaining cases, EUS-TCB provided no tissue (n = 11) or an insufficient amount (n = 7). Logistic regression analysis showed that tumor location on the lesser curvature of the stomach was the only independent predictor of obtaining diagnostic material [odds ratio (OR) 7.4; 95 %CI 1.9 to 28; P = 0.004]. The experience of the endosonographer, the size of the tumor, and the location of the tumor relative to the long axis of the stomach were not related to the success of the biopsy. Agreement between EUS-TCB and surgical pathology specimens in respect of the diagnosis and CD117 status was high (0.9, standard error 0.31; and 0.95, standard error 0.16, respectively); however, there was no correlation between the mitotic index as determined on EUS-TCB and that determined on the surgical pathology specimen (correlation coefficient, 0.08). There were two severe septic complications in 52 procedures (3.9 %; 95 %CI 0.3 % to 14 %). CONCLUSIONS The diagnostic yield of EUS-TCB in patients with gastric SMTs was moderate. Tissue samples were too small to reliably determine the mitotic index. Antibiotic prophylaxis should be considered because of possible septic complications.

Helical computed tomographic cholangiography versus endosonography for suspected bile duct stones: a prospective blinded study in non-jaundiced patients

BACKGROUND Helical computed tomography performed after intravenous administration of a cholangiographic contrast material (HCT-cholangiography) may be useful for detecting bile duct stones in non-jaundiced patients. However, this method has never been compared with other non-invasive biliary imaging tests. AIMS To compare prospectively HCT-cholangiography and endosonography (EUS) in a group of non-jaundiced patients with suspected bile duct stones. METHODS Fifty two subjects underwent both HCT-cholangiography and EUS. Endoscopic retrograde cholangiography (ERCP), with or without instrumental bile duct exploration, served as a reference method, and was successful in all but two patients. RESULTS Thirty four patients (68%) were found to have choledocholithiasis at ERCP. The sensitivity for HCT-cholangiography in stone detection was 85%, specificity 88%, and accuracy 86%. For EUS the sensitivity was 91%, specificity 100%, and accuracy 94%. The differences were not significant. No serious complications occurred with either method. CONCLUSIONS HCT-cholangiography and EUS are safe and comparably accurate methods for detecting bile duct stones in non-jaundiced patients.

A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy

Objective This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. Design We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Results Advanced colorectal neoplasia was detected in 2544 of the 35 918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (p<0.001 for these four factors), and Body Mass Index (p=0.033). In the validation set, the model was well calibrated (ratio of expected to observed risk of advanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7–8. Conclusions Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies.