White light computer-aided optical diagnosis of diminutive colorectal polyps in routine clinical practice.

Background and study aims Artificial Intelligence (AI) systems could make the optical diagnosis (OD) of diminutive colorectal polyps (DCPs) more reliable and objective. This study was aimed at prospectively evaluating feasibility and diagnostic performance of AI-standalone and AI-assisted OD of DCPs in a real-life setting by using a white light-based system (GI Genius, Medtronic Co, Minneapolis, Minnesota, United States). Patients and methods Consecutive colonoscopy outpatients with at least one DCP were evaluated by 11 endoscopists (5 experts and 6 non-experts in OD). DCPs were classified in real time by AI (AI-standalone OD) and by the endoscopist with the assistance of AI (AI-assisted OD), with histopathology as the reference standard. Results Of the 480 DCPs, AI provided the outcome "adenoma" or "non-adenoma" in 81.4% (95% confidence interval [CI]: 77.5-84.6). Sensitivity, specificity, positive and negative predictive value, and accuracy of AI-standalone OD were 97.0% (95% CI 94.0-98.6), 38.1% (95% CI 28.9-48.1), 80.1% (95% CI 75.2-84.2), 83.3% (95% CI 69.2-92.0), and 80.5% (95% CI 68.7-82.8%), respectively. Compared with AI-standalone, the specificity of AI-assisted OD was significantly higher (58.9%, 95% CI 49.7-67.5) and a trend toward an increase was observed for other diagnostic performance measures. Overall accuracy and negative predictive value of AI-assisted OD for experts and non-experts were 85.8% (95% CI 80.0-90.4) vs. 80.1% (95% CI 73.6-85.6) and 89.1% (95% CI 75.6-95.9) vs. 80.0% (95% CI 63.9-90.4), respectively. Conclusions Standalone AI is able to provide an OD of adenoma/non-adenoma in more than 80% of DCPs, with a high sensitivity but low specificity. The human-machine interaction improved diagnostic performance, especially when experts were involved.

Artificial intelligence-assisted optical diagnosis for the resect-and-discard strategy in clinical practice: the Artificial intelligence BLI Characterization (ABC) study.

BACKGROUND: Optical diagnosis of colonic polyps is poorly reproducible outside of high volume referral centers. The present study aimed to assess whether real-time artificial intelligence (AI)-assisted optical diagnosis is accurate enough to implement the leave-in-situ strategy for diminutive (≤ 5 mm) rectosigmoid polyps (DRSPs). METHODS: Consecutive colonoscopy outpatients with ≥ 1 DRSP were included. DRSPs were categorized as adenomas or nonadenomas by the endoscopists, who had differing expertise in optical diagnosis, with the assistance of a real-time AI system (CAD-EYE). The primary end point was ≥ 90 % negative predictive value (NPV) for adenomatous histology in high confidence AI-assisted optical diagnosis of DRSPs (Preservation and Incorporation of Valuable endoscopic Innovations [PIVI-1] threshold), with histopathology as the reference standard. The agreement between optical- and histology-based post-polypectomy surveillance intervals (≥ 90 %; PIVI-2 threshold) was also calculated according to European Society of Gastrointestinal Endoscopy (ESGE) and United States Multi-Society Task Force (USMSTF) guidelines. RESULTS: Overall 596 DRSPs were retrieved for histology in 389 patients; an AI-assisted high confidence optical diagnosis was made in 92.3 %. The NPV of AI-assisted optical diagnosis for DRSPs (PIVI-1) was 91.0 % (95 %CI 87.1 %-93.9 %). The PIVI-2 threshold was met with 97.4 % (95 %CI 95.7 %-98.9 %) and 92.6 % (95 %CI 90.0 %-95.2 %) of patients according to ESGE and USMSTF, respectively. AI-assisted optical diagnosis accuracy was significantly lower for nonexperts (82.3 %, 95 %CI 76.4 %-87.3 %) than for experts (91.9 %, 95 %CI 88.5 %-94.5 %); however, nonexperts quickly approached the performance levels of experts over time. CONCLUSION: AI-assisted optical diagnosis matches the required PIVI thresholds. This does not however offset the need for endoscopists' high level confidence and expertise. The AI system seems to be useful, especially for nonexperts.

Computer-aided detection-assisted colonoscopy: classification and relevance of false positives.

BACKGROUND AND AIMS: False positive (FP) results by computer-aided detection (CADe) hamper the efficiency of colonoscopy by extending examination time. Our aim was to develop a classification of the causes and clinical relevance of CADe FPs, and to assess the relative distribution of FPs in a real-life setting. METHODS: In a post-hoc analysis of a randomized trial comparing colonoscopy with and without CADe (NCT: 04079478), we extracted 40 CADe colonoscopy videos. Using a modified Delphi process, 4 expert endoscopists identified the main domains for the reasons and clinical relevance of FPs. Then, 2 expert endoscopists manually examined each FP and classified it according to the proposed domains. The analysis was limited to the withdrawal phase. RESULTS: The 2 main domains for the causes of CADe FPs were identified as artifacts due to either the mucosal wall or bowel content, and clinical relevance was defined as the time spent on FPs and the FP rate per minute. The mean number of FPs per colonoscopy was 27.3 ± 13.1, of which 24 ± 12 (88%) and 3.2 ± 2.6 (12%) were due to artifacts in the bowel wall and bowel content, respectively. Of the 27.3 FPs per colonoscopy, 1.6 (5.7%) required additional exploration time of 4.8 ± 6.2 seconds per FP (ie, 0.7% of the mean withdrawal time). In detail, 15 (24.2%), 33 (53.2%), and 14 (22.6%) FPs were classified as being of mild, moderate, or severe clinical relevance. The rate of FPs per minute of withdrawal time was 2.4 ± 1.2, and was higher for FPs due to artifacts from the bowel wall than for those from bowel content (2.4 ± 0.6 vs 0.3 ± 0.2, P < .001). CONCLUSIONS: FPs by CADe are primarily due to artifacts from the bowel wall. Despite a high frequency, FPs result in a negligible 1% increase in the total withdrawal time because most of them are immediately discarded by the endoscopist.

Endoscopic technological innovations for neoplasia detection in organized colorectal cancer screening programs: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Many endoscopic technological innovations have claimed to increase the adenoma detection rate (ADR), but their role in population-based organized screening programs is debated. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases through January 2020 for randomized controlled trials (RCTs) evaluating the role of technological innovations in fecal immunochemical test (FIT)/fecal occult blood test+ subjects. The primary outcome was ADR, and secondary outcomes were advanced ADR, proximal colon ADR, mean adenoma per procedure (MAP), and cancer detection rate. We calculated pooled proportion rates (%) or risk ratio with 95% confidence interval (CI) and degree of heterogeneity (I2). RESULTS: Overall, 8 high quality RCTs met inclusion criteria with 3645 patients, 1813 (49.7%) in the intervention arm (advanced imaging, 3 studies; mechanical, 5 studies) and 1832 (50.3%) in the standard colonoscopy arm (mean age, 63.6 years). Pooled ADR was 56.5% (95% CI, 49.9%-62.9%) in the intervention arm and 55.9% (95% CI, 48.6%-63%) in the standard colonoscopy arm (relative risk [RR], 1.01; 95% CI, .93-1.10; I2 = 50.4%). Similarly, no difference was observed for advanced imaging studies (RR, .95; 95% CI, .85-1.07; I2 = 50.4%) or those with mechanical innovations (RR, 1.04; 95% CI, .92-1.17; I2 = 69.49%). The pooled MAP was 1.5 in the intervention arm (95% CI, 1.2-1.8) and 1.5 in the standard colonoscopy (95% CI, 1.1-1.8), with no significant difference (unstandardized mean difference, .04; 95% CI, -.13 to .20; I2 = 53.6%). No difference in advanced ADR, proximal colon ADR, or cancer detection was found. No significant publication bias was found. CONCLUSIONS: In our systematic review and meta-analysis, no technological improvement significantly increased detection rate of colorectal neoplasia in FIT+ subjects undergoing high-quality colonoscopy by high detectors, arguing against their implementation in organized programs.

Efficacy of Real-Time Computer-Aided Detection of Colorectal Neoplasia in a Randomized Trial.

BACKGROUND & AIMS: One-fourth of colorectal neoplasias are missed during screening colonoscopies; these can develop into colorectal cancer (CRC). Deep learning systems allow for real-time computer-aided detection (CADe) of polyps with high accuracy. We performed a multicenter, randomized trial to assess the safety and efficacy of a CADe system in detection of colorectal neoplasias during real-time colonoscopy. METHODS: We analyzed data from 685 subjects (61.32 ± 10.2 years old; 337 men) undergoing screening colonoscopies for CRC, post-polypectomy surveillance, or workup due to positive results from a fecal immunochemical test or signs or symptoms of CRC, at 3 centers in Italy from September through November 2019. Patients were randomly assigned (1:1) to groups who underwent high-definition colonoscopies with the CADe system or without (controls). The CADe system included an artificial intelligence-based medical device (GI-Genius, Medtronic) trained to process colonoscopy images and superimpose them, in real time, on the endoscopy display a green box over suspected lesions. A minimum withdrawal time of 6 minutes was required. Lesions were collected and histopathology findings were used as the reference standard. The primary outcome was adenoma detection rate (ADR, the percentage of patients with at least 1 histologically proven adenoma or carcinoma). Secondary outcomes were adenomas detected per colonoscopy, non-neoplastic resection rate, and withdrawal time. RESULTS: The ADR was significantly higher in the CADe group (54.8%) than in the control group (40.4%) (relative risk [RR], 1.30; 95% confidence interval [CI], 1.14-1.45). Adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07 ±1.54) than in the control group (mean 0.71 ± 1.20) (incidence rate ratio, 1.46; 95% CI, 1.15-1.86). Adenomas 5 mm or smaller were detected in a significantly higher proportion of subjects in the CADe group (33.7%) than in the control group (26.5%; RR, 1.26; 95% CI, 1.01-1.52), as were adenomas of 6 to 9 mm (detected in 10.6% of subjects in the CADe group vs 5.8% in the control group; RR, 1.78; 95% CI, 1.09-2.86), regardless of morphology or location. There was no significant difference between groups in withdrawal time (417 ± 101 seconds for the CADe group vs 435 ± 149 for controls; P = .1) or proportion of subjects with resection of non-neoplastic lesions (26.0% in the CADe group vs 28.7% of controls; RR, 1.00; 95% CI, 0.90-1.12). CONCLUSIONS: In a multicenter, randomized trial, we found that including CADe in real-time colonoscopy significantly increases ADR and adenomas detected per colonoscopy without increasing withdrawal time. ClinicalTrials.gov no: 04079478.

Clinical Validation of BASIC Classification for the Resect and Discard Strategy for Diminutive Colorectal Polyps.

BACKGROUND & AIMS: Blue-light imaging (BLI) is a chromoendoscopy technique that uses direct (not filtered) emission of blue light with short wavelength (410 nm) to increase visibility of microvascular pattern and superficial mucosa. A BLI-based classification system for colorectal polyps (also called BLI Adenomas Serrated International Classification, BASIC) has been created and was validated using still images or short videos. We aimed to validate BASIC in a clinical practice setting, using thresholds recommended by the American Society for Gastrointestinal Endoscopy for the resect and discard strategy as the reference standard. METHODS: We studied 333 patients (mean age, 62.7±8.1 y; 176 men) who underwent screening colonoscopy from January through July 2019. Six endoscopists trained in BASIC participated in the study. All detected diminutive polyps were characterized by real-time BLI and categorized as adenoma or non-adenoma according to BASIC. All polyps were removed and evaluated by histopathology. The BLI-directed surveillance intervals (based on high-confidence characterization of polyps 5 mm or smaller and pathology feature for others) were compared with histology-directed surveillance intervals, according to United States Multi-society Task Force and European Society of Gastrointestinal Endoscopy recommendations. We calculated negative-predictive values of optical real-time analysis of diminutive rectosigmoid adenomas. RESULTS: When we applied BASIC, 748 polyps smaller than 5 mm were categorized with 89% accuracy (95% CI, 85.9%-90.6%). BLI-directed surveillance was correct for 90% of patients according to the United States Multi-society task force criteria (95% CI, 86%-93%) and for 96% of patients according to European Society of Gastrointestinal Endoscopy criteria (95% CI, 93%-97%). The negative-predictive value for 302 polyps smaller than 5 mm, located in the rectosigmoid colon and evaluated with high confidence, based on histologic features of adenomatous polyps, was 91% (95% CI, 85%-95%). CONCLUSIONS: Our analysis of data from 333 patients undergoing screen colonoscopies supports the validity of BASIC discriminating diminutive colorectal polyps with histologic features of adenomas from non-adenomas. This allows for the implementation of the resect and discard strategy based on BLI in clinical practice. ClinicalTrials.gov no: NCT03746171.

Blue-light imaging compared with high-definition white light for real-time histology prediction of colorectal polyps less than 1 centimeter: a prospective randomized study.

BACKGROUND AND AIMS: Blue-light imaging (BLI) is a new chromoendoscopy technique, potentially useful for differentiating neoplastic from nonneoplastic lesions. The present study was aimed at comparing BLI with high-definition white light (HDWL) in the real-time histology prediction of colon polyps <10 mm. METHODS: Consecutive outpatients undergoing colonoscopy with the ELUXEO 7000 endoscopy platform and 760 series video colonoscopes (Fujifilm Co, Tokyo, Japan) who had at least 1 polyp <10 mm were randomized to BLI or HDWL for polyp characterization. The accuracy of high-confidence real-time histology prediction (adenoma vs not adenoma) by either BLI or HDWL for polyps <10 mm (primary end-point) and diminutive (≤5 mm) polyps was calculated, along with sensitivity, specificity, and positive and negative predictive values, with histopathology as the reference standard. RESULTS: A total of 483 polyps were detected in 245 randomized patients (125 and 120 in the BLI and HDWL arms, respectively). A total of 358 were diminutive, and 283 were adenomas. Overall, 222 (85.7%) and 193 (86.1%) polyps were characterized with high confidence by BLI and HDWL, respectively (P = .887), with an overall accuracy of 92% and 84%, respectively (P = .011). The accuracy was significantly higher by BLI than HDWL, also for diminutive polyps (92% vs 83%; P = .008). When BLI was used, the negative predictive value for diminutive rectosigmoid polyps was 88%, and the post-polypectomy surveillance interval was correctly attributed in 85.7% and 93.7% of patients, respectively, according to U.S. and European guidelines. CONCLUSION: BLI was superior to HDWL for the real-time prediction of histology in polyps <10 mm. A BLI-dedicated classification might further improve the endoscopist performance. (Clinical trial registration number: NCT03274115.).

Bowel Preparation for Gastrointestinal Endoscopic Procedures With Sodium Picosulphate-Magnesium Citrate Is an Effective, Safe, and Well-Tolerated Option in Pediatric Patients: A Single-Center Experience.

To obtain optimal visualization of the colonic mucosa during gastrointestinal endoscopic procedures, an adequate bowel preparation is mandatory, but a standardized protocol is still lacking for pediatric patients. Polyethylene glycol (PEG) is currently the most used laxative, but the amount of liquid to be taken orally is a large volume for the pediatric population and it may not be well tolerated. The aim of our preliminary trial was to evaluate efficacy, tolerability, and safety of sodium picosulphate-magnesium citrate (SPMC) used as bowel preparation before colonoscopy in children. Fifty children who needed a colonoscopy were prospectively enrolled between April and December 2013 and SPMC was administered to them as bowel preparation. A questionnaire about the product tolerance was completed by the patients' parents. The grade of bowel preparation and any related side effect were evaluated. The mean value of the Boston Bowel Preparation Scale was 7, out of a maximum of 9. Only 5 patients had an inadequate bowel preparation. Seventy percent of the patients considered the taste of the preparation very palatable. The remaining 26% considered it not palatable or not palatable at all. During the preparation, 18% of children complained of nausea, 20% abdominal pain, 2% vomiting, and 2% manifested headache. Bowel preparation with SPMC offers an efficient alternative to PEG and allows, on equal terms of efficacy, tolerability and safety, a much lower amount of laxative to ingest, and remarkable quality, especially in infants and toddlers.

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.

BACKGROUND: Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. METHODS: We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs (≥200 mg/day) and furosemide (≥25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008-000625-19, and ClinicalTrials.gov, number NCT01288794. FINDINGS: From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0·028), resulting in a 38% reduction in the mortality hazard ratio (0·62 [95% CI 0·40-0·95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3-4 non-liver related adverse events. INTERPRETATION: In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. FUNDING: Italian Medicine Agency.

Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study.

BACKGROUND: Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI). METHODS: Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate. RESULTS: Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively (P < 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group (P = 0.01). CONCLUSIONS: LCI could reduce the miss rate of neoplastic lesions in the right colon.

Educational strategies for colonoscopy bowel prep overcome barriers against split-dosing: A randomized controlled trial.

BACKGROUND: A split-dose (SD) regimen is crucial for colonoscopy quality. Compliance with SD for early morning colonoscopy is generally poor. The present study evaluated whether pre-colonoscopy counselling, in addition to a dedicated leaflet, might increase SD uptake. METHODS: Consecutive 50-69-year-old patients undergoing screening colonoscopy before 10 a.m. were randomized to either receive written information only on bowel preparation (Written Group, WG) or written and oral instructions (Written and Oral Group, WaOG). The leaflet strongly encouraged SD adoption. The primary endpoint was the number of patients adopting SD in each group. The secondary endpoints were predictors of SD uptake, compliance with preparation schemes and cleansing adequacy. RESULTS: A total of 286 patients (143 WG, 143 WaOG) were enrolled (mean age 59.6 ± 6.1 years, men 49.3%). SD was adopted by 114 and 125 patients in the WG and WaOG, respectively (79.7% versus 87.4%, p = 0.079). No significant differences were observed for the proportion of patients with full compliance with preparation scheme (97.9% versus 97.2%, p = 0.99) and of procedures with adequate bowel cleansing (95.6% versus 95.1%, p = 0.77). At multivariate analysis, a > 1 h travel time to the endoscopy service was inversely correlated with SD uptake (odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09-0.98). CONCLUSIONS: Our leaflet guaranteed satisfactory uptake of SD and excellent adherence to the preparation scheme for early morning colonoscopy. Its use might marginalize the need for additional oral instructions, particularly in open-access settings.

Technical interventions to increase adenoma detection rate in colonoscopy.

INTRODUCTION: Adenoma detection rate (ADR) is the most robust colonoscopy quality metric and clinical studies have adopted it as the ideal method to assess the impact of technical interventions. Areas covered: We reviewed papers focusing on the impact of colonoscopy technical issues on ADR, including withdrawal time and technique, second evaluation of the right colon, patient positional changes, gastrointestinal assistant participation during colonoscopy, water-aided technique, optimization of bowel preparation and antispasmodic administration. Expert commentary: Overall, technical interventions are inexpensive, available worldwide and easy to implement. Some of them, such as the adoption of split dose regimen and slow scope withdrawal to allow a careful inspection, have been demonstrated to significantly improve ADR. Emerging data support the use of water-exchange colonoscopy. According to published studies, other technical interventions seem to provide only marginal benefit to ADR. Unfortunately, the available evidence has methodological limitations, such as small sample sizes, the inclusion of expert endoscopists only and the evaluation of single technical interventions. Additionally, larger studies are needed to clarify whether these interventions might have a higher benefit on low adenoma detectors and whether the implementation of a bundle of them, instead of a single technical maneuver, might have a greater impact on ADR.

Narrow-band imaging in the prediction of surveillance intervals after polypectomy in community practice.

BACKGROUND AND STUDY AIMS: It has been proposed that the use of narrow-band imaging (NBI) for real-time histological assessment to determine postpolypectomy surveillance intervals is a cost-effective approach to the management of diminutive polyps. However, significant discrepancies in NBI performance have been observed among endoscopists; hence, professional societies recommend training, monitoring, and auditing. The aim of the present study was to evaluate the performance of real-time optical diagnosis for diminutive polyps after the inclusion of this approach in an internal quality assurance program, in order to assess its applicability in clinical practice Patients and methods: Four endoscopists attended periodic training sessions on NBI assessment of polyp histology before and during the study. Performance was audited and periodic feedback was provided. The accuracy of high-confidence NBI evaluation for polyps ≤ 5 mm in predicting surveillance intervals according to the European and US guidelines, and the negative predictive value (NPV) for adenoma in the rectosigmoid were calculated and compared with recommended thresholds (90 % agreement and 90 % NPV, respectively). RESULTS: Overall, 284 outpatients (mean age 61.3 ±â€Š18.2 years; 63 % males) were enrolled. A total of 656 polyps were detected, 465 of which (70.9 %) were diminutive (70.5 % adenomas). Sensitivity, specificity, positive and negative predictive values, and accuracy of high-confidence NBI predictions for adenoma in diminutive lesions were 95.3 %, 83.5 %, 93.5 %, 87.6 %, and 91.9 %, respectively. High-confidence characterization of diminutive polyps predicted the correct surveillance interval in 95.8 % and 93.3 % of cases according to European and American guidelines, respectively. NPV for adenoma in the rectosigmoid was 91.3 % CONCLUSIONS: For community settings in which endoscopists are adequately trained and performance is periodically audited, real-time optical diagnosis for diminutive polyps is sufficiently accurate to avoid postpolypectomy histological examination of resected lesions, or to leave rectosigmoid hyperplastic polyps in place. Trial registered at ClinicalTrials.gov (NCT02196402).

Adrenal function and microbial DNA in noninfected cirrhotic patients with ascites: Relationship and effect on survival.

BACKGROUND: There are few data on clinical relevance of adrenal dysfunction and its relationship with occult microbial DNA in noninfected haemodynamically stable cirrhotic patients with ascites. AIMS: The aim of this study was to evaluate prognostic role of adrenal dysfunction, microbial DNA, and their relationship. METHODS: Adrenal function was assessed in 93 consecutive patients following a corticotropin stimulation test. Adrenal dysfunction was defined as: basal cortisol <10 µg/dl, delta cortisol <9 µg/dl, or peak cortisol <18 µg/dl. Microbial DNA was assessed in blood and ascites of 54 consecutive patients. Patients were followed up until liver transplantation or death. RESULTS: Adrenal dysfunction was not significantly associated with mortality, while the risk of death rose significantly with an increase in basal cortisol values (HR 1.13 per 1-µl/dl increase; 95% CI 1.01-1.26). Microbial DNA was independently associated with reduced survival (HR 8.05, 95% CI 1.57-41.2). In microbial DNA-positive patients a significant correlation was found between Model for End-Stage Liver Disease (MELD) score and basal cortisol values (Pearson's r=0.5107; p=0.018). CONCLUSIONS: Microbial DNA and MELD score, but not adrenal function, were the best independent predictors of mortality in noninfected cirrhotic patients with ascites. High serum cortisol levels may be a systemic reaction to microbial translocation, increasing in parallel with deterioration of liver function.

A multicentre case control study on complicated coeliac disease: two different patterns of natural history, two different prognoses.

BACKGROUND: Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. METHODS: Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. RESULTS: 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. CONCLUSIONS: Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.

Terlipressin and albumin for type-1 hepatorenal syndrome associated with sepsis.

BACKGROUND & AIMS: Terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections. However, there is no information on efficacy and safety of this treatment in patients with type-1 HRS associated with sepsis. Study aim was to investigate the effects of early treatment with terlipressin and albumin on circulatory and kidney function in patients with type-1 HRS and sepsis and assess factors predictive of response to therapy. METHODS: Prospective study in 18 consecutive patients with type-1 HRS associated with sepsis. RESULTS: Treatment was associated with marked improvement in arterial pressure and suppression of the high levels of plasma renin activity and norepinephrine. Response to therapy (serum creatinine <1.5mg/dl) was achieved in 12/18 patients (67%) and was associated with improved 3-month survival compared to patients without response. Non-responders had significantly lower baseline heart rate, poor liver function tests, slightly higher serum creatinine, and higher Child-Pugh and MELD scores compared to responders. Interestingly, non-responders had higher values of CLIF-SOFA score compared to responders (14±3 vs. 8±1, respectively p<0.001), indicating greater severity of acute-on-chronic liver failure (ACLF). A CLIF-SOFA score ⩾11 had 92% sensitivity and 100% specificity in predicting no response to therapy. No significant differences were observed between responders and non-responders in baseline urinary kidney biomarkers. Treatment was safe and no patient required withdrawal of terlipressin. CONCLUSIONS: Early treatment with terlipressin and albumin in patients with type-1 HRS associated with sepsis is effective and safe. Patients with associated severe ACLF are unlikely to respond to treatment.

PROgnosticating COeliac patieNts SUrvivaL: the PROCONSUL score.

INTRODUCTION: It has been shown that mortality rates of coeliac patients correlate with age at diagnosis of coeliac disease, diagnostic delay for coeliac disease, pattern of clinical presentation and HLA typing. Our aim was to create a tool that identifies coeliac patients at higher risk of developing complications. METHODS: To identify predictors of complications in patients with coeliac disease, we organised an observational multicenter case-control study based on a retrospective collection of clinical data. Clinical data from 116 cases (patients with complicated coeliac disease) and 181 controls (coeliac patients without any complications) were collected from seven European centres. For each case, one or two controls, matched to cases according to the year of assessment, gender and age, were selected. Diagnostic delay, pattern of clinical presentation, HLA typing and age at diagnosis were used as predictors. RESULTS: Differences between cases and controls were detected for diagnostic delay and classical presentation. Conditional logistic models based on these statistically different predictors allowed the development of a score system. Tertiles analysis showed a relationship between score and risk of developing complications. DISCUSSION: A score that shows the risk of a newly diagnosed coeliac patient developing complications was devised for the first time. This will make it possible to set up the follow-up of coeliac patients with great benefits not only for their health but also for management of economic resources. CONCLUSIONS: We think that our results are very encouraging and represent the first attempt to build a prognostic score for coeliac patients.

Role of bowel ultrasound as a predictor of surgical recurrence of Crohn's disease.

BACKGROUND: In Crohn's disease natural history, about 80% of the patients require surgery, which is not curative: unfortunately, the disease recurs in many patients. OBJECTIVE: To investigate the role of intestinal ultrasound to predict the risk of post-operative surgical recurrence in Crohn's disease. MATERIAL AND METHODS: A total of 196 patients, with ileal or ileocolonic Crohn's disease, undergoing intestinal resection, were retrospectively enrolled. All patients underwent bowel ultrasonography 6-15 months after resection. Wall thickness at the anastomosis level was measured, and thickening >3 mm was evaluated as risk factor of long-term need for reoperation. RESULTS: Patients who have a bowel wall thickness >3 mm have an risk ratio (RR) of surgical recurrence = 2.1 [95% confidence interval (CI) = 1.12-3.74] higher than those with a thickness of ≤3 mm. The absolute incidence of new surgical intervention is 13% in patients with thickness of 3 mm, 28% in patients with thickness >3 mm, 29,1% with thickness >4 mm, 34% with thickness >5 mm, and 40% with thickness >6 mm. CONCLUSIONS: Bowel wall thickness >3 mm at ultrasound may be a non-invasive predictor of early surgical recurrence after ileo-colonic resection.

Quality of life in coeliac patients: Italian validation of a coeliac questionnaire.

BACKGROUND: Coeliac disease (CD) is a chronic condition requiring a gluten-free diet, which is a very demanding diet to maintain on a life-long basis. For this reason it is a condition that can have serious repercussions on the quality of life (QOL). Therefore the need to elaborate a questionnaire on QOL specifically for patients with CD (CDQ): its original language is German, and the translation/validation process represents a considerable challenge involving not only a translation into Italian but also an adaptation to the country's specific cultural differences. METHODS: The questionnaire has been translated according to a "German → Italian → Italian → German" algorithm with reconciliation of the differences. Scores for CDQ are computed overall and over four areas of four items each: emotion, gastrointestinal symptoms, gastrointestinal worries, social problems. RESULTS: CDQ was administered to 171 coeliacs (F 132, mean age 38 yrs ± 14). Completeness was optimal. Item internal consistency was satisfied for 100% and 97% of patients for the specific and generic part, respectively. Cronbach's α coefficient was 0.7 for all scales. The general CDQ was higher in patients reporting subjective well-being (discriminant validity). CONCLUSIONS: The Italian translation of CDQ sounds natural, is easy to understand and reduces possible cultural biases to a minimum. A field test gave results comparable to the original validation, supporting the use of CDQ in cross-national surveys.