Vicent Hernandez

Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening

BACKGROUND Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).

Unstimulated salivary flow rate, pH and buffer capacity of saliva in healthy volunteers

OBJECTIVES To assess the salivary flow rate, pH, and buffer capacity of healthy volunteers, and their relationships with age, gender, obesity, smoking, and alcohol consumption, and to establish the lower-end value of normal salivary flow (oligosialia). METHODS A prospective study was conducted in 159 healthy volunteers (age > 18 years, absence of medical conditions that could decrease salivary flow). Unstimulated whole saliva was collected during ten minutes, and salivary flow rate (ml/min), pH, and bicarbonate concentration (mmol/l) were measured using a Radiometer ABL 520. The 5 percentile of salivary flow rate and bicarbonate concentration was considered the lower limit of normality. RESULTS Median salivary flow rate was 0.48 ml/min (range: 0.1-2 ml/min). Age younger than 44 years was associated with higher flow rates (OR 2.10). Compared with women, men presented a higher flow rate (OR 3.19) and buffer capacity (OR 2.81). Bicarbonate concentration correlated with salivary flow rate. The lower-end values of normal flow rate and bicarbonate concentration were 0.15 ml/min and 1.800 mmol/l, respectively. The presence of obesity, smoking, and alcohol consumption did not influence salivary parameters. CONCLUSIONS In healthy volunteers, salivary flow rate depends on age and gender, and correlates with buffer capacity. Obesity, smoking, and alcohol use do not influence salivary secretion.

Dental and periodontal lesions in patients with gastro-oesophageal reflux disease

OBJECTIVE Dental erosion has been considered an extraesophageal manifestation of gastro-oesophageal reflux disease, but few reports have studied the relationship between this disease and other periodontal or dental lesions. The aim of this study was to investigate the prevalence of dental and periodontal lesions in patients with gastro-oesophageal reflux disease. PATIENTS AND METHODS A total of 253 subjects were prospectively studied between April 1998 and May 2000. Two study groups were established: 181 patients with gastro-oesophageal reflux disease and 72 healthy volunteers. Clinical assessment, including body mass index and consumption of tobacco and alcohol, was performed in all subjects, as well as a dental and periodontal examination performed by a dentist physician, blind as to the diagnosis of subjects. Parameters evaluated were: (a) presence and number of dental erosion, location and severity, according to the Eccles and Jenkins index [Prosthet Dent 1979;42:649-53], modified by Hattab [Int J Prosthes 2000;13:101-71; (b) assessment of dental condition by means of the CAO index; and (c) periodontal status analysed by the plaque index, the haemorrhage index, and gingival recessions. RESULTS Clinical parameters were similar in both groups (p > 0.05). Age was statistically associated with the CAO index, presence of dental erosion, and gingival recession (p < 0.001, Students t-test). Compared with the control group, the percentage of dental erosion was significantly higher in the gastro-oesophageal reflux disease group (12.5 vs. 47.5%, p < 0.001, chi2-test), as was the number and severity of dental erosions (p < 0.001, Students t-test). Location of dental erosion was significantly different between groups. Age was not statistically related to either the amount or severity of dental erosion. CAO and periodontal indices were similarly distributed between groups. CONCLUSIONS Dental erosion may even be considered as an extraesophageal manifestation of gastro-oesophageal reflux disease. The fact that the prevalence of caries and periodontal lesions is similar in patients with gastro-oesophageal reflux disease and in healthy volunteers suggests a lack of relationship with gastro-oesophageal reflux disease.

Infliximab salvage therapy after failure of ciclosporin in corticosteroid-refractory ulcerative colitis: a multicentre study

Aliment Pharmacol Ther 2012; 35: 275–283

Recurrence of acute gallstone pancreatitis and relationship with cholecystectomy or endoscopic sphincterotomy.

OBJECTIVES:To determine the prevalence of recurrence of gallstone pancreatitis, its clinical features, and the presence of prognostic factors of recurrence.METHODS:From January 1, 2000 to August 31, 2003, 233 patients admitted with acute gallstone pancreatitis (AGP) were prospectively studied. Patients were divided into two groups: recurrent and nonrecurrent group. Clinical, analytical, radiological, prognostic parameters, and severity (Atlanta criteria) were assessed, along with the performance of cholecystectomy or endoscopic sphincterotomy (ES). Clinical features of recurrence were analyzed. Univariate (χ2, Students t-test) and multivariate tests were performed. Statistical significance was assumed if p < 0.05.RESULTS:Two hundred and eighty-six attacks were identified. Forty-two patients (18.2%) recurred, suffering 53 recurrent attacks, which took place within 30 days in 23.3%. Patients who did not undergo surgery after the first attack had 31-fold risk of recurrence (OR = 31.5%, CI = 95%[7.22–137.84], p < 0.001). In patients not operated, recurrence was more frequent if ES was not performed (37.04%vs 0%, p= 0.019). Among patients with surgical risk, none who recurred underwent ES, compared with 27.9% of those who did not recur. Patients in the nonrecurrent group underwent cholecystectomy within the first 30 days or ES more frequently (31.2%vs 7.3%, p= 0.001).CONCLUSIONS:Recurrence of gallstone pancreatitis is a frequent event. Delay of cholecystectomy implies an increased risk of recurrence. ES could be an acceptable option to prevent recurrence in patients who are not candidates for surgery or who do not desire to undergo cholecystectomy.

Initial disease course and treatment in an inflammatory bowel disease inception cohort in Europe: The ECCO-EpiCom cohort

Background:The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort. Methods:Patients were followed-up every third month during the first 12 (±3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu). Results:In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn’s disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe. Discussion:In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.

Fecal immunochemical test accuracy in average-risk colorectal cancer screening.

AIM To assess the fecal immunochemical test (FIT) accuracy for colorectal cancer (CRC) and advanced neoplasia (AN) detection in CRC screening. METHODS We performed a multicentric, prospective, double blind study of diagnostic tests on asymptomatic average-risk individuals submitted to screening colonoscopy. Two stool samples were collected and the fecal hemoglobin concentration was determined in the first sample (FIT1) and the highest level of both samples (FITmax) using the OC-sensor™. Areas under the curve (AUC) for CRC and AN were calculated. The best FIT1 and FITmax cut-off values for CRC were determined. At this threshold, number needed to scope (NNS) to detect a CRC and an AN and the cost per lesion detected were calculated. RESULTS About 779 individuals were included. An AN was found in 97 (12.5%) individuals: a CRC in 5 (0.6%) and an advanced adenoma (≥ 10 mm, villous histology or high grade dysplasia) in 92 (11.9%) subjects. For CRC diagnosis, FIT1 AUC was 0.96 (95%CI: 0.95-0.98) and FITmax AUC was 0.95 (95%CI: 0.93-0.97). For AN, FIT1 and FITmax AUC were similar (0.72, 95%CI: 0.66-0.78 vs 0.73, 95%CI: 0.68-0.79, respectively, P = 0.34). Depending on the number of determinations and the positivity threshold cut-off used sensitivity for AN detection ranged between 28% and 42% and specificity between 91% and 97%. At the best cut-off point for CRC detection (115 ng/mL), the NNS to detect a CRC were 10.2 and 15.8; and the cost per CRC was 1814€ and 2985€ on FIT1 and FITmax strategies respectively. At this threshold the sensitivity, NNS and cost per AN detected were 30%, 1.76, and 306€, in FIT1 strategy, and 36%, 2.26€ and 426€, in FITmax strategy, respectively. CONCLUSION Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.

Usefulness of oral beclometasone dipropionate in the treatment of active ulcerative colitis in clinical practice: The RECLICU Study

BACKGROUND Beclometasone dipropionate (BDP) is a relatively new topically acting oral steroid to treat mild to moderately active ulcerative colitis (UC). We estimate that 20,000 patients have received oral BDP in Spain in the last two years. Our aim was to evaluate the efficacy and safety of oral BDP in clinical practice. METHODS Retrospective and multicenter study that included 434 patients with active UC treated with BDP. The partial Mayo Clinic score (pMS, 0-9) was used to measure disease activity. Remission was defined as post-treatment pMS of 0 or 1; response as a decrease in pMS of 3 points or 2 points and >30%, and failure as lack of remission or response. RESULTS BDP dose was 5 mg/day in 88% of patients and mean treatment duration was 6.2 weeks. BDP achieved remission in 44.4%, response in 22.3% and failed in 33.2% of patients. Mean pMS decreased from 4.9 ± 1.3 to 2.4 ± 2.3 (p<0.0001). Remission rate was higher in mild and moderate than in severe UC (p<0.043) and tended to be higher in left-sided and extensive UC than in proctitis (p<0.06). Failure was less frequent in patients treated for >4 weeks (p<0.02). Mild adverse events were reported in 7.6% of patients. CONCLUSION BDP induces response or remission in two thirds of active UC patients, with a good safety profile. Patients with mild to moderate, left-sided or extensive UC, receiving BDP for more than 4 weeks are most likely to benefit from this treatment.

Risk of Advanced Proximal Neoplasms According to Distal Colorectal Findings: Comparison of Sigmoidoscopy-Based Strategies

BACKGROUND Screening for colorectal cancer with sigmoidoscopy benefits from the fact that distal findings predict the risk of advanced proximal neoplasms (APNs). This study was aimed at comparing the existing strategies of postsigmoidoscopy referral to colonoscopy in terms of accuracy and resources needed. METHODS Asymptomatic individuals aged 50-69 years were eligible for a randomized controlled trial designed to compare colonoscopy and fecal immunochemical test. Sigmoidoscopy yield was estimated from results obtained in the colonoscopy arm according to three sets of criteria of colonoscopy referral (from those proposed in the UK Flexible Sigmoidoscopy, Screening for COlon REctum [SCORE], and Norwegian Colorectal Cancer Prevention [NORCCAP] trials). Advanced neoplasm detection rate, sensitivity, specificity, and number of individuals needed to refer for colonoscopy to detect one APN were calculated. Logistic regression analysis was performed to identify distal findings associated with APN. All statistical tests were two-sided. RESULTS APN was found in 255 of 5059 (5.0%) individuals. Fulfillment of UK (6.2%), SCORE (12.0%), and NORCCAP (17.9%) criteria varied statistically significantly (P < .001). The NORCCAP strategy obtained the highest sensitivity for APN detection (36.9%), and the UK approach reached the highest specificity (94.6%). The number of individuals needed to refer for colonoscopy to detect one APN was 6 (95% confidence interval [CI] = 4 to 7), 8 (95% CI = 6 to 9), and 10 (95% CI = 8 to 12) when the UK, SCORE, and NORCCAP criteria were used, respectively. The logistic regression analysis identified distal adenoma ≥10 mm (odds ratio = 3.77; 95% CI = 2.52 to 5.65) as the strongest independent predictor of APN. CONCLUSIONS Whereas the NORCCAP criteria achieved the highest sensitivity for APN detection, the UK recommendations benefited from the lowest number of individuals needed to refer for colonoscopy.

Fecal immunochemical test accuracy in familial risk colorectal cancer screening

There is little information on fecal immunochemical test (FIT) in familial risk colorectal cancer (CRC) screening. Our study assesses FIT accuracy, number needed to scope (NNS) and cost to detect a CRC and an advanced neoplasia (AN) in this setting. We performed a multicentric, prospective, double‐blind study of diagnostic tests on individuals with first‐degree relatives (FDRs) with CRC submitted to screening colonoscopy. Two stool samples were collected and fecal hemoglobin in the first sample (FIT1) and the highest in both samples (FITmax) were determined. Areas under the curve (AUC) for CRC and AN as well as the best FIT1 and FITmax cutoff value for CRC were determined. At this threshold, NNS and the cost per lesion detected were calculated. A total of 595 individuals were included (one FDR > 60 years, 413; two FDR or one ≤ 60 years, 182). AN and CRC were found in 64 (10.8%) and six (1%) patients, respectively. For CRC diagnosis, FIT1 AUC was 0.96 [95% confidence interval (CI): 0.95–0.98] and FITmax AUC was 0.95 (95% CI: 0.93–0.97). For AN diagnosis, FIT1 and FITmax AUC were 0.74 (95% CI: 0.66–0.82). The best cutoff point for CRC was 115. At this threshold, the NNS to detect a CRC was 5.67 and 7.67, and the cost per CRC was 1,064€ and 1591.33€ on FIT1 and FITmax strategies, respectively. FIT shows high accuracy to detect CRC in familial CRC screening. Performing two tests does not improve diagnostic accuracy, but increases cost and NNS to detect a lesion.