Fabio Monica

Changing trends in acute upper-GI bleeding: a population-based study.

BACKGROUND Advances in medical practice in recent decades have influenced the etiology and management of acute upper-GI bleeding (UGIB), but their impact on the incidence and mortality is unclear. OBJECTIVE To analyze the time trends of UGIB in 2 different management eras. DESIGN Prospective observational study. SETTING General university-affiliated hospital. PATIENTS AND INTERVENTIONS A total of 587 patients who presented with UGIB during the 1983-to-1985 period were compared with 539 patient in the 2002-to-2004 period. RESULTS The overall incidence of UGIB decreased from 112.5 to 89.8 per 100,000/y, which corresponds to a 35.5% decrease after adjustment for age (95% CI, 24.2%-46.8%). The age standardized incidence of ulcer bleeding decreased by 41.6% (95% CI, 27.2%-56%); the decrease occurred only in people younger than 70 years of age. The rate of history of peptic ulcer disease decreased from 32.7% in the 1983-to-1985 period versus 19.5% in the 2002-to-2004 period (P < .001). The mean age increased from 61.0 to 68.7 years (P < .001), and the male:female ratio decreased from 2.7 to 1.8 (P = .002). The comorbidities increased from 69% to 75% (P = .01), the use of nonsteroidal anti-inflammatory drugs from 40.0% to 46.4% (P = .03), and the cases of bleeding occurring during hospitalization from 10.4% to 17.1% (P < .001). In the 1983-to-1985 cohort, the endoscopy was solely diagnostic, and antisecretory therapy consisted of H2-antagonists drugs. In the second period, 39.3% of patients underwent endoscopic therapy, whereas proton pump inhibitors were administered in 47%. Rebleeding rates decreased from 32.5% to 7.4% (P < .001) and surgery from 10.2% to 2.0% (P < .001). Overall mortality decreased from 17.1 to 8.2 per 100,000/y, which corresponded to a 60.8% decrease after adjustment for age (95% CI, 46.5%-75.1%). The age standardized mortality rate for ulcer bleeding decreased by 56.5% (95% CI, 41.9%-71.1%). LIMITATIONS A single-center study and a potential lack of generalizability. CONCLUSIONS From the 1983-to-1985 period to the 2002-to-2004 period, major changes occurred in the incidence of UGIB, features of patients, management, and outcomes. The incidence and mortality of UGIB overall and ulcer bleeding decreased significantly, and the decline of incidence occurred only in patients younger than 70 years old.

Prophylaxis of ERCP-related pancreatitis: A randomized, controlled trial of somatostatin and gabexate mesylate

BACKGROUND & AIMS It still is debated whether post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be prevented by administering either somatostatin or gabexate mesylate. The aim of the study is to assess the efficacy of a 6.5-hour infusion of somatostatin or gabexate mesylate in preventing ERCP-related complications. METHODS In a double-blind multicenter trial, 1127 patients undergoing ERCP were randomly assigned to intravenous administration of somatostatin (750 microg; n = 351), gabexate mesylate (500 mg; n = 381), or placebo (saline; n = 395). The drug infusion started 30 minutes before and continued for 6 hours after endoscopy. Patients were evaluated clinically, and serum amylase levels were determined at 4, 24, and 48 hours after endoscopy. RESULTS No significant differences in incidences of pancreatitis, hyperamylasemia, or abdominal pain were observed among the placebo (4.8%, 32.6%, and 5.3%, respectively), somatostatin (6.3%, 26.8%, and 5.1%, respectively), and gabexate mesylate groups (5.8%, 31.5%, and 6.3%, respectively). Univariate analysis of patient characteristics and endoscopic maneuvers showed that a Freeman score >1 (P < 0.0001), >/=3 pancreatic injections (P < 0.00001), and precut sphincterotomy (P = 0.01) were significantly associated with post-ERCP pancreatitis. At multiple logistic regression analysis, >/=3 pancreatic injections (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.45-2.63) and a Freeman score >1 (OR, 1.47; 95% CI, 1.11-1.94) retained their predictive power. CONCLUSIONS Long-term (6.5-hr) administration of either somatostatin or gabexate mesylate is ineffective for the prevention of post-ERCP pancreatitis. Pancreatic injury seems to be related to difficulty in common bile duct access.

High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: A multicentre, randomized study

BACKGROUND:The most effective schedule of proton pump inhibitor (PPI) administration following endoscopic hemostasis of bleeding ulcers remains uncertain.METHODS:Patients with actively bleeding ulcers and those with nonbleeding visible vessel or adherent clot were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to an intensive regimen (80 mg bolus followed by 8 mg/h as continuous infusion for 72 h) or a standard regimen (40 mg bolus daily followed by saline infusion for 72 h). After the infusion, all patients were given 20 mg PPI twice daily orally. The primary end point was the in-hospital rebleeding rate, as ascertained at the repeat endoscopy.RESULTS:Bleeding recurred in 28 of 238 patients (11.8%) receiving the intensive regimen, and in 19 of 236 (8.1%) patients receiving the standard regimen (P = 0.18). Most rebleeding episodes occurred during the initial 72-h infusion: 18 (7.6%) and 19 events (8.1%) in the intensive and standard groups, respectively (P = 0.32). Mean units of blood transfused were 1.7 ± 2.1 in the intensive and 1.5 ± 2.1 in the standard regimen group (P = 0.34). The duration of hospital stay was <5 days for 88 (37.0%) and 111 patients (47.0%) in the intensive and standard groups (P = 0.03). There were fewer surgical interventions in the standard versus intensive regimen (1 vs 3). Five patients in each treatment group died.CONCLUSIONS:Following endoscopic hemostasis of bleeding ulcers, standard-dose PPIs infusion was as effective as a high-dose regimen in reducing the risk of recurrent bleeding. (ClinicalTrials.gov number, NCT00374101).

Gallstone disease in an elderly population: the Silea study.

BACKGROUND Little is known on gallbladder emptying and gallstone composition in the elderly. AIMS AND SUBJECTS: Cross-sectional survey on the prevalence of gallstone disease and associated factors, gallstone characteristics and gallbladder emptying in a population aged > or = 60 years. METHODS Gallstone number and size as well as gallbladder motor function were assessed by ultrasound. Gallstone composition and pattern were evaluated by conventional radiology and computed tomography (CT) based on Hounsfield units (HU). RESULTS Gallstones were found in 148/1,065 subjects (13.9%), while 136 subjects (12.8%) were cholecystectomized with an overall prevalence of gallstone disease of 26.7% (sex ratio: F > M). Multiple gallstones (62.7%) and small gallstones (52%, diameter < or = 15 mm) were seen; silent gallstones accounted for 93.9% of the total. Only diabetes mellitus in women was significantly associated with cholelithiasis. Gallbladder fasting volumes were larger in gallstone carriers than in controls (P < 0.01); residual and ejection volumes were also significantly greater in gallstone carriers, whereas ejection fractions were similar in the two groups (50.3% +/- 2.4 versus 54.9% +/- 3.0; not significant). Gallstone calcifications were detected in 29/91 gallstone carriers by X-ray and in another 20 by CT (HU > 90). Moreover, 35 gallstone carriers had a score < or = 50 HU and six had attenuation values between 50 and 90 HU. Six gallstone patterns were identified: hypo-isodense, homogeneously dense, rimmed, laminated, core-hyperdense, gas-containing. CONCLUSIONS In the elderly, the prevalence of gallstone disease is very high, especially in women, but gallstone size, number and pattern and gallbladder emptying do not differ from those reported in the middle-aged gallstone population. Advanced age is associated with a high rate of calcified, probably pigment stones.

Bleeding peptic ulcer occurring in hospitalized patients: analysis of predictive and risk factors and comparison with out-of-hospital onset of hemorrhage.

We reviewed 84 consecutive cases of peptic ulcer hemorrhage, which occurred, in an area of 270,000 people, from 1986 to 1988, in patients already hospitalized for other diseases (in-bleeders). These subjects were compared with a prospective series of 386 patients who initially bled as out-patients and were then admitted (out-bleeders). Of 84 hemorrhages in hospitalized patients, 41 followed major surgery, while 43 were associated with other severe conditions. Bleeding site was duodenal in two thirds. Mean age was 67 ± 15 years versus 59 ± 15 among out-bleeders. Fifty percent of in-bleeders had recently received nonsteroidal antiinflammatory drugs (NSAIDs), and one third were on anticoagulants and 10% on corticosteroids; in 39 (46%) bleeding was shown to be persistent or recurrent, 5 (5.9%) underwent endoscopic and 18 (21%) surgical therapy; 29 died (34%). The corresponding figures among out-bleeders were: further bleeding 80 (20.7%), endoscopic therapy 12 (3.1%), surgery 25 (6.5%), deaths 17 (4.4%). As regards in-bleeders, only active bleeding and endoscopic stigmata emerged as statistically significant risk factors for further bleeding. The latter was shown to be significantly related to mortality. The most relevant finding was, however, that NSAIDs and anticoagulants, in association with stress and aging, are very frequently involved in peptic ulcer bleeding of hospitalized patients. The fatal outcome of one third, despite all available treatments, highlights the importance of prevention against drug- and stress-related mucosal damage in in-patients suffering from severe diseases.

Comparison between different colon cleansing products for screening colonoscopy. A noninferiority trial in population-based screening programs in Italy.

BACKGROUND AND STUDY AIMS The high volume and poor palatability of 4 L of polyethylene glycol (PEG)-based bowel cleansing preparation required before a colonoscopy represent a major obstacle for patients. The aim of this study was to compare two low volume PEG-based preparations with standard 4 L PEG in individuals with a positive fecal immunochemical test (FIT) within organized screening programs in Italy. PATIENTS AND METHODS A total of 3660 patients with a positive FIT result were randomized to receive, in a split-dose regimen, 4 L PEG or 2 L PEG plus ascorbate (PEG-A) or 2 L PEG with citrate and simethicone plus bisacodyl (PEG-CS). The noninferiority of the low volume preparations vs. 4 L PEG was tested through the difference in proportions of adequate cleansing. RESULTS A total of 2802 patients were included in the study. Adequate bowel cleansing was achieved in 868 of 926 cases (93.7 %) in the 4 L PEG group, in 872 out of 911 cases in the PEG-A group (95.7 %, difference in proportions  + 1.9 %, 95 % confidence interval [CI]  - 0.1 to 3.9), and in 862 out of 921 cases in the PEG-CS group (93.6 %, difference in proportions  - 0.2 %, 95 %CI  - 2.4 to 2.0). Bowel cleansing was adequate in 95.5 % of cases when the preparation-to-colonoscopy interval was between 120 and 239 minutes, whereas it dropped to 83.3 % with longer intervals. Better cleansing was observed in patients with regular bowel movements (95.6 %) compared with those with diarrhea (92.4 %) or constipation (90.8 %). CONCLUSION Low volume PEG-based preparations administered in a split-dose regimen guarantee noninferior bowel cleansing compared with 4 L PEG. Constipated patients require a personalized preparation. TRIAL REGISTRATION EudraCT 2012 - 003958 - 82.

Comparative Efficacy of Colonoscope Distal Attachment Devices in Increasing Rates of Adenoma Detection: A Network Meta-analysis

BACKGROUND & AIMS Several add‐on devices have been developed to increase rates of colon adenoma detection (ADR). We assessed their overall and comparative efficacy, and estimated absolute magnitude of benefit through a network meta‐analysis. METHODS We searched the PubMed/Medline and Embase database through March 2017 and identified 25 randomized controlled trials (comprising 16,103 patients) that compared the efficacy of add‐on devices (cap; Endocuff; Arc Medical Design Ltd, Leeds, UK, and Endorings; Us Endoscopy, Mentor, OH) with each other or with standard colonoscopy. The primary outcome was ADR; secondary outcomes included rate of polyp detection, and rate of and time to cecal intubation. We performed pairwise and network meta‐analyses, and appraised quality of evidence using Grading of Recommendations Assessment, Development and Evaluation. We estimated the magnitude of increase in ADR by low‐performing endoscopists (baseline ADR, 10%) and high‐performing endoscopists (baseline ADR, 40%) with use of these devices. RESULTS Overall, distal attachment devices increased ADR compared with standard colonoscopy (relative risk [RR], 1.13; 95% CI, 1.03–1.23; low‐quality evidence), with potential absolute increases in ADR to 11.3% for low‐performing endoscopists and to 45.2% for high‐performing endoscopists. In a comparative evaluation, we found low‐quality evidence that Endocuff increases ADR compared with standard colonoscopy (RR, 1.21; 95% CI, 1.03–1.41), with anticipated increases in ADR to 12% for low‐performing endoscopists and to 48% for high‐performing endoscopists. We found very low quality evidence to support the use of Endorings (RR, 1.70; 95% CI, 0.86–3.36) or caps (RR, 1.07; 95% CI, 0.96–1.19) vs standard colonoscopy for increasing ADR. The benefit of one distal attachment device over another was uncertain due to very low quality evidence. CONCLUSIONS Based on network meta‐analysis, we anticipate only modest improvement in ADRs with use of distal attachment devices, especially in low‐performing endoscopists.

Clean Colon Software Program (CCSP), Proposal of a standardized Method to quantify Colon Cleansing During Colonoscopy: Preliminary Results

Background and study aims: Neoplastic lesions can be missed during colonoscopy, especially when cleansing is inadequate. Bowel preparation scales have significant limitations and no objective and standardized method currently exists to establish colon cleanliness during colonoscopy. The aims of our study are to create a software algorithm that is able to analyze bowel cleansing during colonoscopies and to compare it to a validate bowel preparation scale. Patients and methods: A software application (the Clean Colon Software Program, CCSP) was developed. Fifty colonoscopies were carried out and video-recorded. Each video was divided into 3 segments: cecum-hepatic flexure (1st Segment), hepatic flexure-descending colon (2nd Segment) and rectosigmoid segment (3rd Segment). Each segment was recorded twice, both before and after careful cleansing of the intestinal wall. A score from 0 (dirty) to 3 (clean) was then assigned by CCSP. All the videos were also viewed by four endoscopists and colon cleansing was established using the Boston Bowel Preparation Scale. Interclass correlation coefficient was then calculated between the endoscopists and the software. Results: The cleansing score of the prelavage colonoscopies was 1.56 ± 0.52 and the postlavage one was 2,08 ± 0,59 (P < 0.001) showing an approximate 33.3 % improvement in cleansing after lavage. Right colon segment prelavage (0.99 ± 0.69) was dirtier than left colon segment prelavage (2.07 ± 0.71). The overall interobserver agreement between the average cleansing score for the 4 endoscopists and the software pre-cleansing was 0.87 (95 % CI, 0.84 – 0.90) and post-cleansing was 0.86 (95 % CI, 0.83 – 0.89). Conclusions: The software is able to discriminate clean from non-clean colon tracts with high significance and is comparable to endoscopist evaluation.

PWE-008 Colorectal cancer screening programs and the rate of surgical oncology procedures in the veneto region (italy)

Introduction Colorectal cancer (CRC) is a leading cause of cancer mortality in the Veneto Region (North-east Italy). Population screening of adults between 50 and 75 for CRC was begun in 2002, and it became standard practice in all 21 local health units (LHU) of the region in 2008, 14 LHU provided in the program also follow-up colonoscopy and 7 LHU no. This study was carried out to evaluate the impact on surgery rates of CRC screening and follow-up programs. Method This is a retrospective cohort study on administrative data based on anonymous computerised database of Veneto Region hospital discharges between 2000 and 2015. All Veneto residents (in screening age) discharge records with principal diagnosis of CRC treated with surgery were included in the study. The number of patients studied rose approximately 18% reaching 1,547,097 for the last year (2015). The Standardised Hospitalisation Ratio (SHR) per five-year age group was calculated and expressed per 10 000 population. Results During the study period, 30 399 surgical procedures for colorectal cancer were performed (colon 63%, rectum 36%, secondary malignant neoplasm 1%) with a SHR of 139.1, higher in males (OR: 1.66; CI 95%: 1.62–1.7; p<0.05). An analysis of the annual SHR distribution uncovered two distinct phases: during the first phase there was a rising tendency that reached a maximum value in 2007 (166,9; X2 trend: 46.731; p<0.05) and during the second there was a falling tendency that reached its minimum value in 2015 (102.3; X2 trend: 429.791; p<0.05), with a total reduction of 28%. The cancer stratification by site shows that the rate of surgical procedures of the proximal colon during the last year was the same as the 2000 value (41.5), instead there was a significant decrease (−37,3%; X2 trend: 559.282; p<0.05) in the rate of procedures on the distal colon and rectum which fell from 94.4 to 59.2 (Figure1). The stratification of LHU in which the screening program included a follow-up colonoscopy and others didn’t show significant difference in the reduction in surgical procedures (Figure2). Abstract PWE008 Figure 1 Abstract PWE-008 Figure 2 Conclusion Study findings confirmed that CRC screening was effective in reducing the number of oncological surgical oncology procedures particularly with regard to the distal colon and rectum. Data analysis showed that the screening seemed to accelerate reaching the peak rate in surgical procedures that took place in 2007. After that time point the number of operations began to fall as far as the distal colon was concerned (it fell by 37.3%). Finally data suggest that the real benefit in reduction of oncological surgery procedures is due to the first screening colonoscopy. Disclosure of Interest None Declared

115 Impact on Colorectal Cancer Mortality of Screening Programmes Based on Immunochemical Fecal Occult Blood Test in the Veneto Region (Italy)

Background There is evidence that colorectal cancer (CRC) screening programmes based on guaiac fecal occult blood test reduce CRC-specific mortality. Several studies showed higher performances of fecal immunochemical test (FIT) compared to guaiac test. In Italy most CRC screening programmes utilize FIT, but data on their impact on mortality are lacking. Methods In the Veneto Region (north-east of Italy), FIT screening programmes were activated in different areas between 2002 and 2009. Subjects 50-69 years old are invited every two years to perform FIT and, if positive, are referred to colonoscopy. We compared CRC mortality between areas where screening was activated in 2002-2004 (early screening areas ESA) and in 2008-2009 (late screening areas LSA). For ESA and LSA we computed CRC mortality rates of 50-74 years old subjects in 2002-2011 and the Annual Percent Change (APC), with 95% Confidence intervals (CI95%). The association between mortality time trends and screening activation was evaluated by a Poisson regression model with an interaction term between year and area, adjusting for age and gender. To evaluate whether changes in mortality reflected different underlying incidence rates, we analyzed CRC incidence from 1995 to 2006 (last year available) of the two areas included in the Veneto Cancer Registry. Results The mid-period 50-74yrs resident population of ESA and LSA was respectively 288,125 and 357,486. In the study period CRC mortality rates in ESA declined from 45.7 per 100,000 in 2002 to 36.2 in 2011. In LSA mortality was stable around 45 per 100,000 (FIgure 1).The APC was -3.5% (CI95% -5.3% to -1.6%) in ESA and -0.5% (CI95% -2.5% to 1.5%) in LSA. Poisson regression showed a significant interaction between area and year, with a 2.8% (p=0.029) reduction of mortality rates attributable to screening per year. The estimated reduction of CRC mortality in ESA vs LSA was 25% over the whole study period. However, the association between area and mortality rates was observed only in females (6.2% annual reduction, p=0.004) but not in males. The incidence rates in LSA progressively increased between 1995 and 2006, with a APC of +1.4% (CI95% 0.8% to 2.0%) over the whole period. The ESA showed an increase between 2000 and 2003 (APC +9.9%; CI95% 5.9% to 14.1%) followed by a steep reduction (APC -22.4%; CI95% -35.1% to -7.4%)(Figure 2). Conclusion The ESA showed a 25% reduction of CRC mortality compared to the LSA, independent from underlying incidence rates. This ecological study represents one of the first evidences of the impact on mortality of FIT screening programmes. Further research on this topic is needed.