Living donor liver transplantation can address disparities in transplant access for patients with primary sclerosing cholangitis.

BACKGROUND: Liver transplantation (LT) is frequently lifesaving for people living with primary sclerosing cholangitis (PSC). However, patients are waitlisted for LT according to the model for end-stage liver disease-sodium (MELD-Na) score, which may not accurately reflect the burden of living with PSC. We sought to describe and analyze the clinical trajectory for patients with PSC referred for LT, in a mixed deceased donor/living donor transplant program. METHODS: This was a retrospective cohort study from November 2012 to December 2019, including all patients with PSC referred for assessment at the University Health Network Liver Transplant Clinic. Patients who required multiorgan transplant or retransplantation were excluded. Liver symptoms, hepatobiliary malignancy, MELD-Na progression, and death were abstracted from chart review. Competing risk analysis was used for timing of LT, transplant type, and death. RESULTS: Of 172 PSC patients assessed, 84% (n = 144) were listed of whom 74% were transplanted. Mean age was 47.6 years, and 66% were male. Overall mortality was 18.2% at 2 years. During the follow-up, 16% (n = 23) were removed from the waitlist for infection, clinical deterioration, liver-related mortality or new cancer; 3 had clinical improvement. At listing, 82% (n = 118) had a potential living donor (pLD). Patients with pLD had significantly lower waitlist and liver-related waitlist mortality (HR 0.20, p<0.001 and HR 0.17, p<0.001, respectively), and higher rates of transplantation (HR 1.83, p = 0.05). Exception points were granted to 13/172 (7.5%) patients. CONCLUSIONS: In a high-volume North American LT center, most patients with PSC assessed for transplant were listed and subsequently transplanted. However, this was a consequence of patients engaging in living donor transplantation. Our findings support the concern from patients with PSC that MELD-Na allocation does not adequately address their needs.

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation.

BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001). CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Effect of Linked-color Imaging on the Detection of Adenomas in Screening Colonoscopies.

OBJECTIVES: Linked-color imaging (LCI) is a new image-enhancement option that emphasizes mucosal surface contrast, facilitating the differentiation between colorectal lesions and normal mucosa. This study aimed to evaluate the potential of LCI to increase the detection of colorectal adenomas in screening colonoscopies. METHODS: A prospective randomized study was conducted using white-light imaging (WLI), blue-laser imaging (BLI)-bright and LCI. The outcome measures were adenoma detection rate (ADR), mean number of adenomas per patient, and withdrawal time. Lesion characteristics such as size, morphology, location, and histology were also evaluated. RESULTS: A total of 205 patients were randomized, and 251 adenomas were detected. The overall ADR was 62%. The ADR was 52.9% for WLI, 62.1% for BLI-bright, and 71% for LCI, and was significantly higher in the LCI group than in the WLI group (P=0.04). No significant difference was observed between LCI and BLI-bright (P=0.28) or BLI-bright and WLI (P=0.30). The mean number of adenomas per patient was 1.01, 1.03, and 1.62 for WLI, BLI-bright, and LCI, respectively, with a significant difference (P=0.02). Withdrawal time did not differ among the groups. A total of 71 adenomas were detected by WLI, 68 by BLI-bright, and 112 by LCI. There was no difference in the size and morphology of the adenomas detected, nor in the diagnosis of sessile serrated adenomas/polyps. CONCLUSION: LCI significantly increased the detection of adenomas in screening colonoscopies.

Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease.

Reliable and available non-invasive methods for hepatic fibrosis assessment are important in chronic liver disease (CLD). Our aim was to compare stepwise algorithms combining standard ultrasound with serum markers and transient elastography (TE) for detecting advanced fibrosis (F3-4) and cirrhosis. Retrospective single center study between 2012 and 2018 of CLD patients with biopsy, TE, blood tests, and liver ultrasound parameters of surface nodularity (SN), lobar redistribution, and hepatic vein nodularity. Our cohort included 157 patients (51.6% males), mean age 47.6 years, predominantly non-alcoholic fatty liver disease and viral hepatitis (61%), with F3-4 prevalence of 60.5%. Area under the curve for F3-4 was 0.89 for TE ≥ 9.6 kPa and 0.80 for FIB-4 > 3.25. In multivariate modeling, TE ≥ 9.6 kPa (OR 21.78) and SN (OR 3.81) had independent association with F3-4; SN (OR 5.89) and TE ≥ 10.2 kPa (OR 15.73) were independently associated with cirrhosis. Two stepwise approaches included FIB-4 followed by SN or TE; sensitivity and specificity of stepwise SN were 0.65 and 1.00, and 0.89 and 0.33 for TE ≥ 9.6 kPa, respectively. Ultrasound SN and TE were independently predictive of F3-4 and cirrhosis in our cohort. FIB-4 followed by SN had high specificity for F3-4.

Single-Center North American Experience of Liver Transplantation in Autoimmune Hepatitis: Infrequent Indication but Good Outcomes for Patients.

BACKGROUND AND AIMS: A 40% risk of disease recurrence post-liver transplantation (LT) for autoimmune hepatitis (AIH) has been previously reported. Risk factors for recurrence and its impact on long-term patient outcome are poorly defined. We aimed to assess prevalence, time to disease recurrence, as well as patient and graft survival in patients with recurrent AIH (rAIH) versus those without recurrence. METHODS: Single-center retrospective study of adult recipients who underwent LT for AIH between January 2007 and December 2017. Patients with AIH overlap syndromes were excluded. RESULTS: A total of 1436 LTs were performed during the study period, of whom 46 (3%) for AIH. Eight patients had AIH overlap syndromes and were excluded. Patients were followed up for 4.4 ± 3.4 years and mean age at LT was 46.8 years. Average transplant MELD (Model for End-Stage Liver Disease) score was 24.9. About 21% of patients (8 of 38) were transplanted for acute onset of AIH; 66% of patients (n = 25) received a deceased donor liver graft, and 34% a living donor organ. rAIH occurred in 7.8% (n = 3/38) of recipients. Time to recurrence was 1.6, 12.2 and 60.7 months. Patient and graft survival in patients without recurrence was 88.6% and 82.8% in 5 years, whereas in those with rAIH, it was 66.7%, respectively. CONCLUSION: Although AIH recurs post-LT, our data indicate a lower recurrence rate when compared to the literature and excellent patient and graft survival.

Salvage Therapy with Sofosbuvir/Velpatasvir/Voxilaprevir in DAA-experienced Patients: Results from a Prospective Canadian Registry.

BACKGROUND: Despite the current highly effective therapies with direct-acting antiviral agents (DAAs), some patients with chronic hepatitis C virus (HCV) infection still do not achieve sustained virological response (SVR) and require retreatment. Sofosbuvir/velpatasvir/voxilaprevir (SVV) is recommended as the first-line retreatment option for most patients. The aim of this study was to evaluate the efficacy of SVV as salvage therapy after at least one course of DAA. METHODS: Data were collected on all HCV-infected patients who failed DAAs and were prescribed SVV from a prospective Canadian registry (CANUHC) including 17 sites across Canada. Factors associated with failure to achieve SVR with SVV therapy and the utility of RAS testing and ribavirin use were evaluated. RESULTS: A total of 128 patients received SVV after non-SVR with DAA treatment: 80% male, median age 57.5 (31-86), 44% cirrhotic, and 17 patients post liver transplant. First line regimens included: sofosbuvir/velpatasvir (27.3%), sofosbuvir/ledipasvir (26.5%), grazoprevir/elbasvir (12.5%), other (33.5%). Ribavirin was added to SVV in 26 patients due to past sofosbuvir/velpatasvir use (n = 8), complex resistance associated substitution profiles (n = 16) and/or cirrhosis (n = 9). Overall SVR rate was 96% (123/128). Of 35 patients who previously failed sofosbuvir/velpatasvir, 31 (88.5%) achieved SVR compared to 92 of 93 (99%) among those receiving any other regimen (P = .01). CONCLUSIONS: Similar to reports from phase 3 clinical trials, SVV proved highly effective as salvage therapy for patients who failed a previous DAA therapy. Those who failed SVV had at least 2 of the following factors: genotype 3, presence of cirrhosis, past liver transplantation, past exposure to sofosbuvir/velpatasvir and/or complex resistance profiles.

Biliary cannulation with contrast and guide-wire versus exclusive guide-wire: A prospective, randomized, double-blind trial.

BACKGROUND: The use of exclusive guide-wire cannulation (e-GW) instead of contrast injection reduces post-ERCP pancreatitis (PEP) and pre-cutting and increases cannulation rate. Herein, we intend to compare e-GW with the hybrid technique (GW-C and/or contrast injection). METHODS: Prospective single-center randomized comparative study, which included all patients referred to ERCP to our unit. Patients with non-naïve papilla; previous ERCP; direct infundibulotomy, ampullectomy, Billroth II gastrectomy or pancreatic sphincterotomy and patients lost to follow up were excluded. RESULTS: 727 consecutive patients were assessed. Of these, 588 naïve papilla patients were included and randomized to receive e-GW (n = 299) or GW-C (n = 289) for selective biliary cannulation. The mean age was 60.3 years and 60.5% were women. PEP occurred in 15(5%) cases in e-GW group and 9(3.1%) in the GW-C group (p = 0.29). Time to reach deep cannulation was faster in the latter group (75% < 5 min vs. 50.2% < 5 min, p<0.001). > 10 min until cannulation was observed in 21% vs. 10% of the ERCPs (groups e-GW and GW-C, respectively, p < 0.001). Total ERCP time was also shorter in the GW-C group (12 vs. 10 min; p < 0.001). Pre-cut (23.8 vs.11.8%, p < 0.001) and pancreatic sphincterotomy as a pre-cut technique (15.8 vs. 5.6%, p < 0.001) were used more frequently in the e-GW group. CONCLUSIONS: Compared to exclusive G-W- assisted biliary cannulation, the hybrid technique did not significantly reduce the PEP rate, however it promoted faster cannulation and, consequently, reduced the total procedure time and the use of pre-cut techniques.

Single Topic Conference on Autoimmune Liver Disease from the Canadian Association for the Study of the Liver.

Autoimmune liver disease (AILD) spans a spectrum of chronic disorders affecting the liver parenchyma and biliary system. Three main categories of AILD are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). This review condenses the presentation and discussions of the Single Topic Conference (STC) on AILD that was held in Ottawa, Ontario, in November 2019. We cover generalities regarding disease presentation and clinical diagnosis; mechanistic themes; treatment paradigms; clinical trials, including approaches and challenges to new therapies; and looking beyond traditional disease boundaries. Although these diseases are considered autoimmune, the etiology and role of environmental triggers are poorly understood. AILDs are progressive and chronic conditions that affect survival and quality of life. Advances have been made in PBC treatment because second-line treatments are now available (obeticholic acid, bezafibrate); however, a significant proportion still present suboptimal response. AIH treatment has remained unchanged for several decades, and data suggest that fewer than 50% of patients achieve a complete response and as many as 80% develop treatment-related side effects. B-cell depletion therapy to treat AIH is in an early stage of development and has shown promising results. An effective treatment for PSC is urgently needed. Liver transplant remains the best option for patients who develop decompensated cirrhosis or hepatocellular carcinoma within specific criteria, but recurrent AILD might occur. Continued efforts are warranted to develop networks for AILD aimed at assessing geo-epidemiological, clinical, and biochemical differences to capture the new treatment era in Canada.

Endoscopic Biliary Large Balloon Dilation Lithotripsy for Giant and Impacted Stones Removal: A Western Series.

BACKGROUND: Endoscopic removal of packed, large, or impacted stones, in which a basket cannot be deployed or is unable to grasp the stone(s), is challenging and inevitably leads to repeated procedures such as stent insertion and extra- or intracorporal lithotripsy. In this study, we describe the results of an alternative stone disintegration technique in a considerable series of patients using an esophageal/pyloric balloon for stone fragmentation or making working space in the bile duct to allow the deployment of the basket, a technique we call endoscopic biliary large balloon lithotripsy. METHODS: We retrieved data from 1,429 endoscopic retrograde cholangiopancreatographies (ERCPs) from 2 prospective trials performed between 2014 and 2019. Patients with difficult bile duct stones, in which a balloon dilator up to 15 mm was used to crush or increase the working space parallel to the stones in the common or hepatic duct, were included in the study. RESULTS: From the 1,429 ERCPs, 299 had difficult stones (>1 cm, impacted or multiple stones). Large balloon lithotripsy was employed in 46 cases after endoscopic papillotomy and endoscopic biliary large balloon dilation with failed attempted balloon or basket stone(s) extraction. Failure to clear the bile duct at first ERCP occurred in 4 cases (91.3% of success). Complications were observed in 5 patients (10.8%; 1 perforation, 1 pancreatitis, and 3 bleedings), who were treated conservatively. CONCLUSIONS: Large balloon lithotripsy, in order to crush the stones or make working room for baskets or balloons in the bile duct, is an effective, safe, and low cost technique for impacted, packed, or giant bile duct stones.

Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.

BACKGROUND: An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors. METHODS: HCV-uninfected organ recipients without pre-existing liver disease were treated with ezetimibe (10 mg; an HCV entry inhibitor) and glecaprevir-pibrentasvir (300 mg/120 mg) before and after transplantation from HCV-infected donors aged younger than 70 years without co-infection with HIV, hepatitis B virus, or human T-cell leukaemia virus 1 or 2. Recipients received a single dose 6-12 h before transplant and once a day for 7 days after surgery (eight doses in total). HCV RNA was assessed once a day for 14 days and then once a week until 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection, as evidenced by undetectable serum HCV RNA at 12 weeks after transplant, and assessed in the intention-to-treat population. Safety monitoring was according to routine post-transplant practice. 12-week data are reported for the first 30 patients. The trial is registered on ClinicalTrials.gov, NCT04017338. The trial is closed to recruitment but follow-up is ongoing. FINDINGS: 30 patients (23 men and seven women; median age 61 years (IQR 48-66) received transplants (13 lung, ten kidney, six heart, and one kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5·11 log10IU/mL (IQR 4·55-5·63) and at least three HCV genotypes were represented (nine [50%] donors with genotype 1, two [11%] with genotype 2, five [28%] with genotype 3, and two [11%] with unknown genotype). All 30 (100%) transplant recipients met the primary endpoint of undetectable HCV RNA at 12 weeks post-transplant, and were HCV RNA-negative at last follow-up (median 36 weeks post-transplant [IQR 25-47]). Low-level viraemia was transiently detectable in 21 (67%) of 30 recipients in the early post-transplant period but not after day 14. Treatment was well tolerated with no dose reductions or treatment discontinuations; 32 serious adverse events occurred in 20 (67%) recipients, with one grade 3 elevation in alanine aminotransferase (ALT) possibly related to treatment. Non-serious transient elevations in ALT and creatine kinase during the study dosing period resolved with treatment completion. Among the serious adverse events were two recipient deaths due to causes unrelated to study drug treatment (sepsis at 49 days and subarachnoid haemorrhage at 109 days post-transplant), with neither patient ever being viraemic for HCV. INTERPRETATION: Ezetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors. FUNDING: Canadian Institutes of Health Research; the Organ Transplant Program, University Health Network.

The Pathophysiology of Cholestasis and Its Relevance to Clinical Practice.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-hirschfield a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-interview-hirschfield an interview with the author https://www.wileyhealthlearning.com/Activity/7058609/disclaimerspopup.aspx questions and earn CME.

Efficacy of endoscopic treatments for acute esophageal variceal bleeding in cirrhotic patients: systematic review and meta-analysis.

Background and aim Guidelines recommend use of ligation and vasoactive drugs as first-line therapy and as grade A evidence for acute variceal bleeding (AVB), although Western studies about this issue are lacking. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy of endoscopic treatments for AVB in patients with cirrhosis. Trials that included patients with hepatocellular carcinoma, use of portocaval shunts or esophageal resection, balloon tamponade as first bleeding control measure, or that received placebo or elective treatment in one study arm were excluded. Results A total of 8382 publications were searched, of which 36 RCTs with 3593 patients were included. Ligation was associated with a significant improvement in bleeding control (relative risk [RR] 1.08; 95 % confidence interval [CI] 1.02 - 1.15) when compared to sclerotherapy. Sclerotherapy combined with vasoactive drugs showed higher efficacy in active bleeding control compared to sclerotherapy alone (RR 1.17; 95 % CI 1.10 - 1.25). The combination of ligation and vasoactive drugs was not superior to ligation alone in terms of overall rebleeding (RR 2.21; 95 %CI 0.55 - 8.92) and in-hospital mortality (RR 1.97; 95 %CI 0.78 - 4.97). Other treatments did not generate meta-analysis. Conclusions This study showed that ligation is superior to sclerotherapy, although with moderate heterogeneity. The combination of sclerotherapy and vasoactive drugs was more effective than sclerotherapy alone. Although current guidelines recommend combined use of ligation with vasoactive drugs in treatment of esophageal variceal bleeding, this study failed to demonstrate the superiority of this combined treatment.

Impact of linked-color imaging on colorectal adenoma detection.

BACKGROUND AND AIMS: Linked-color imaging (LCI) is a new technology that emphasizes changes in mucosal color by providing clearer and brighter images, thus allowing red and white areas to be visualized more clearly. We investigated whether LCI increases the detection of colorectal adenomas compared with white-light imaging (WLI) and blue-laser imaging (BLI)-bright. METHODS: Consecutive patients undergoing colonoscopy were randomized (1:1:1) into examination by WLI, BLI-bright, or LCI during withdrawal of the colonoscope. The adenoma detection rate (ADR), mean number of adenomas per patient, and withdrawal time were evaluated. The lesions were evaluated according to size, morphology, location, and histology. RESULTS: A total of 379 patients were randomized, and 412 adenomas were detected. The ADR was 43.2%, 54.0%, and 56.9% for WLI, BLI-bright, and LCI, respectively, and was significantly higher in the LCI group than in the WLI group (P = .03). No significant difference was observed between LCI and BLI-bright (P = .71) or BLI-bright and WLI (P = .09). The mean number of adenomas per patient was 0.82, 1.06, and 1.38 for WLI, BLI-bright, and LCI, respectively, with a significant difference between LCI and WLI (P = .03). Withdrawal time did not differ among the groups. A total of 102 adenomas were detected by WLI, 131 by BLI-bright, and 179 by LCI. LCI provided a higher rate of detection of adenomas ≤5 mm in size than WLI (P = .02), with a borderline significance for a higher detection of sessile serrated adenomas (P = .05). Nonpolypoid adenomas were more commonly located in the right colon segment and polypoid adenomas in the left colon segment, with a significant difference only between BLI-bright (P < .01) and LCI (P = .03). CONCLUSIONS: Our findings show that LCI increases the detection of colorectal adenomas during colonoscopy. (Clinical trial registration number: RBR-9xg6dx.).

A Practical Review of Primary Biliary Cholangitis for the Gastroenterologist.

Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic liver disease characterized by biliary destruction and progressive intrahepatic cholestasis. PBC primarily affects women in their fifth or sixth decade of life. Although many patients are asymptomatic at presentation, fatigue, pruritus, sicca syndrome, and upper abdominal discomfort are common symptom manifestations. The etiology of PBC is thought to be related to interactions between underlying genetic predisposition and microbial and xenobiotic environmental triggers. The diagnosis is established in the setting of biochemical cholestasis and antimitochondrial or disease-specific antinuclear antibodies, with histologic evidence of nonsuppurative granulomatous cholangitis being supportive, but not required, to confirm disease. Care of patients with PBC encompasses therapies to slow disease progression, manage symptoms associated with cholestasis, and treat complications of advanced liver disease. Risk stratification based on simple clinical and laboratory parameters, either as binary response criteria and/or continuous models, helps identify the patients at greatest risk of poor outcome. First-line therapy to slow disease progression is ursodeoxycholic acid (UDCA), which is the mainstay of pharmacologic therapy for all patients with PBC. The only currently approved second-line option for patients who do not achieve adequate biochemical response or are intolerant to UDCA is the novel farnesoid X receptor agonist obeticholic acid. Off-label use of peroxisome proliferator-activated receptor agonists, including the fibrate class of drugs where available, is also recognized as an option for patients.

Blue laser imaging: a new image-enhanced endoscopy for the diagnosis of colorectal lesions.

BACKGROUND: Image-enhanced endoscopy enables real-time differential diagnosis of colorectal lesions through the observation of microvascular architecture. PURPOSE: To evaluate the efficacy of using blue laser imaging (BLI) for capillary pattern analysis in the differential diagnosis of neoplastic and non-neoplastic lesions. PATIENTS AND METHODS: This prospective study included 920 consecutive superficial lesions diagnosed in 457 patients. The capillary pattern was analysed using BLI-bright magnification on the basis of the Teixeira classification. Histopathology was used as the reference standard. RESULTS: The adenoma detection rate was 42.3%, with a mean of 0.95 adenomas per patient. Neoplastic lesions were predominant (70.3%), of which 33 (5.1%) had advanced histology. Neoplastic progression was significantly increased in patients aged at least 50 years, in lesions at least 10 mm and in lesions located in the right colon (P<0.01). BLI-based capillary pattern analysis showed 95.5% accuracy, 95.7% sensitivity, 95.2% specificity, 97.9% positive predictive value and 90.3% negative predictive value in the diagnosis of neoplastic lesions. For 672 diminutive lesions (≤5 mm), BLI-based capillary pattern analysis showed 95.7% accuracy, 96.6% sensitivity, 93.6% specificity, 97.2% positive predictive value and 92.2% negative predictive value. Analysing only lesions up to 5 mm in the rectum and sigmoid colon, the values were 95.2, 93.9, 96.5, 95.8 and 94.8%, respectively. CONCLUSION: BLI associated with magnification yielded excellent results for the real-time predictive histological diagnosis of colorectal lesions.

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial.

OBJECTIVES:: The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. METHODS:: In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. RESULTS:: A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). CONCLUSION:: The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR.

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial

OBJECTIVES: The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. METHODS: In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. RESULTS: A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). CONCLUSION: The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR.

Prophylaxis of pancreatitis with intravenous ketoprofen in a consecutive population of ERCP patients: a randomized double-blind placebo-controlled trial.

Background Acute pancreatitis is the most common complication after ERCP, occurring in about 4 % of the procedures. Only the placement of pancreatic duct prosthesis and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) have shown benefit in the prevention of post-ERCP pancreatitis (PEP). Although the benefit of rectal administration of indomethacin or diclofenac is recommended by some studies and society guidelines especially in a selected group of high-risk patients, there is so far, no standardization of time or route of NSAID administration. The aim of the current study is to investigate the role of an intravenous NSAID administered before the procedure for PEP prevention. Methods In this randomized double-blind clinical trial, all consecutive patients who underwent ERCP were randomized to receive saline infusion with ketoprofen or saline, immediately before the procedure. Results A total of 477 patients were enrolled and completed follow-up. The majority of patients (72.1 %) had bile duct stones, and only 1.5 % had a clinical suspicion of sphincter of Oddi dysfunction. PEP developed in 5 of 253 (2 %) patients in the placebo group and in 5 of 224 (2.2 %) patients in the ketoprofen group (p = 1.). Conclusions Intravenous administration of ketoprofen immediately prior to ERCP did not result in reduction in PEP in a general population of ERCP patients.

IMPACT OF THE PEGYLATED-INTERFERON AND RIBAVIRIN THERAPY ON THE TREATMENT-RELATED MORTALITY OF PATIENTS WITH CIRRHOSIS DUE TO HEPATITIS C VIRUS.

UNLABELLED: Although the protease inhibitors have revolutionized the therapy of chronic hepatitis C (CHC), the concomitant use of pegylated-interferon (PEG-IFN) and ribavirin (RBV) is associated to a high rate of adverse effects. In this study, we evaluated the consequences of PEG-IFN and RBV and their relationship with mortality in patients with cirrhosis. METHODS: Medical records of CHC who underwent treatment with PEG-IFN and RBV in a public hospital in Brazil were evaluated. All the patients with cirrhosis were selected, and their clinical and laboratory characteristics, response to treatment, side effects and mortality were evaluated. RESULTS: From the 1,059 patients with CHC, 257 cirrhotic patients were evaluated. Of these, 45 (17.5%) achieved sustained viral response (SVR). Early discontinuation of therapy occurred in 105 (40.8%) patients, of which 39 (15.2%) were due to serious adverse effects. The mortality rate among the 257 cirrhotic patients was 4.3%, occurring in 06/242 (2.4%) of the Child-A, and in 05/15 (33.3%) of the Child-B patients. In conclusion, the treatment of patients with cirrhosis due to HCV with PEG-IFN and RBV shows a low SVR rate and a high mortality, especially in patients with liver dysfunction.

Large Colorectal Lesions: Evaluation and Management.

In the last years, a distinctive interest has been raised on large polypoid and non-polypoid colorectal tumors, and specially on flat neoplastic lesions ≥20 mm tending to grow laterally, the so called laterally spreading tumors (LST). Real or virtual chromoendoscopy, endoscopic ultrasound or magnetic resonance should be considered for the estimation of submucosal invasion of these neoplasms. Lesions suitable for endoscopic resection are those confined to the mucosa or selected cases with submucosal invasion ≤1000 µm. Polypectomy or endoscopic mucosal resection remain a first-line therapy for large colorectal neoplasms, whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory.

Nos últimos anos houve um crescente interesse pelas lesões colorretais polipoides e não polipoides de grande tamanho, especialmente pelas lesões planas neoplásicas ≥20 mm que tendem a crescer lateralmente - as chamadas lesões de espraiamento lateral (LST). Para avaliar o acometimento submucoso dessas lesões, pode-se utilizar a cromoendoscopia real ou virtual, a ecoendoscopia e a ressonância magnética. A ressecção endoscópica está indicada em lesões restritas à mucosa ou em casos selecionados com invasão da submucosa ≤ 1000 µm. A polipectomia e a ressecção endoscópica de mucosa permanecem um tratamento de primeira escolha para lesões colorretais grandes, enquanto que as LSTs cuja ressecção em bloco é mandatória devem ser submetidas à dissecção submucosa endoscópica em centros com grande experiência na técnica ou à ressecção cirúrgica.