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Description : Check out this medical presentation on Bile Duct Cancer (Cholangiocarcinoma), which is titled "Endoscopy in PSC", to know about the EASL/ESGE clinical practice guidelines on the role of endoscopy in primary sclerosing cholangitis.

Tags : Bile Duct Cancer, Cholangiocarcinoma, Endoscopy, PSC, EASL, ESGE, clinical practice guidelines, primary sclerosing cholangitis

Published on : May 10, 2021 | Views : 1817 | Downloads : 2

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Slide 1-

Endoscopy in PSC Clinical Practice Guidelines
Slide 2-

About these slides *Current slides 9 and 10 include images which may not be adapted or shared without permission; see slide footnotes for details These slides give a comprehensive overview of the EASL/ESGE clinical practice guidelines on the role of endoscopy in primary sclerosing cholangitis The guidelines were published in full in the April 2017 issue of the Journal of Hepatology and the June 2017 issue of Endoscopy The full publication can be downloaded from the Clinical Practice Guidelines section of the EASL website Please cite the published article as: European Association for the Study of the Liver. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. J Hepatol 2017;66:1265–81 Please feel free to use, adapt, and share these slides for your own personal use, except where noted*; however, please acknowledge EASL as the source
Slide 3-

About these slides Definitions of all abbreviations shown in these slides are provided within the slide notes When you see a home symbol like this one: , you can click on this to return to the outline or topics pages, depending on which section you are in Please send any feedback to: slidedeck_feedback@easloffice.eu These slides are intended for use as an educational resource and should not be used in isolation to make patient management decisions. All information included should be verified before treating patients or using any therapies described in these materials
Slide 4-

Guideline panel ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Chairs ESGE: Lars Aabakken EASL: Tom Hemming Karlsen Panel members Jörg Albert, Marianna Arvanitakis, Olivier Chazouilleres, Jean-Marc Dumonceau, Martti Färkkilä, Peter Fickert, Gideon M Hirschfield, Andrea Laghi, Marco Marzioni, Michael Fernandez, Stephen P Pereira, Jürgen Pohl, Jan-Werner Poley, Cyriel Y Ponsioen, Christoph Schramm, Fredrik Swahn, Andrea Tringali, Cesare Hassan
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Outline ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:126581
Slide 6-

Methods Grading evidence and recommendations
Slide 7-

Grading evidence and recommendations 1. Atkins D, et al. BMC Health Serv Res 2004;4:38; 2. Qaseem A, et al. Ann Intern Med 2010;153:1949; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:126581 Grading is adapted from the GRADE system1 and is in line with that adopted by the American College of Physicians2
Slide 8-

Background Definition, prevalence, pathophysiology Diagnosis ERCP and MRC in PSC
Slide 9-

Definition and prevalence *‘Backwash’ ileitis 1. Karlsen TH, et al. J Hepatol 2017;67:1298–323; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Image © Kari C Toverud CMI 2017. Please do not adapt or share without permission A rare chronic bile duct disease Multifocal bile duct strictures and progressive liver disease1 IBD coexists in most patients1 Prevalence is 1–16 per 100,000 Regional differences across Europe More common in men Most patients present with pancolitis Right-sided predominance Subtle ileal inflammation* and rectal sparing are common Highly increased and unpredictable risk of biliary and colonic malignancy A major challenge in the clinical management of PSC Macroscopic bowel and bile duct pathology in PSC1 ‘Backwash’ ileitis Colonic cancer Pancolitis with right-sided predominance Rectal sparing Cholangiocarcinoma Multifocal bile duct strictures and dilatations
Slide 10-

Overview of pathophysiology1 1. Karlsen TH, et al. J Hepatol 2017;67:1298–323; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Image © Kari C Toverud CMI 2017. Please do not adapt or share without permission >20 susceptibility genes have been identified Role of gut-derived antigens remains unclear Primary or secondary disturbances in bile homeostasis are thought to contribute to PSC T cells, macrophages and neutrophils are likely to engage with an activated cholangiocyte phenotype Chronic injury + common fibrotic mechanisms involving hepatic stellate cells and portal myofibroblasts in an undefined cross-talk with cholangiocytes Liver-related complications in PSC are mainly represented by bile duct strictures, liver cirrhosis and CCA
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Diagnosis of PSC *Dilated bile ducts or focal lesion 1. EASL CPG. Management of cholestatic liver diseases. J Hepatol 2009;51:237–67; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Based on clinical, laboratory, imaging, and histological findings A diagnostic work-up for PSC should be performed in: All patients with IBD and abnormal liver biochemistry Especially elevated ALP and GGT values Non-IBD patients with elevated cholestatic liver enzymes not otherwise explained A proposed algorithm for PSC diagnosis in adult patients with cholestasis is the focus of a different guideline Diagnostic approach to cholestasis in adult patients1
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ERCP and MRC in PSC 1. Weismüller TJ, et al. J Hepatol 2008;48 Suppl 1:S38–57; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 ERCP plays a significant role in PSC High accuracy Prognostic value Sampling and therapeutic possibilities However, ERCP must be integrated within well-defined clinical algorithms with less invasive/ non-invasive tests Widespread use of MRC has restricted ERCP to cases where the diagnosis is equivocal or when sampling or endoscopic treatment are required Patient A: multifocal strictures of the intrahepatic bile ducts and high-grade stenosis at the cystic duct junction. Patient B: long-segment filiform stenosis of the common bile duct ERCP MRC ERCP and MRC in patients with PSC1 A B
Slide 13-

Guidelines Key recommendations
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Endoscopic diagnosis of PSC ERCP in confirmed PSC Relevance of dominant strictures Assessing risk of CCA Therapeutic ERCP PSC and cholangiocarcinoma Brush cytology for identification of CCA Endoscopic surveillance of PSC-associated IBD Topics ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Click on a topic to skip to that section
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Endoscopic diagnosis of PSC Angulo J, et al. Hepatol 2000;33:5207; Moff SL, et al. Gastrointest Endosc 2006;64:21923; Vittelas AJR, et al. AJR Am J Roentgenol 2002;179:399407; Talwalker JA. Hepatology 2004;40:3945; Dave M. Radiology 2010;256:38796 ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Diagnostic performance of MRC vs. ERCP Comparable accuracy: 90% vs. 97% MRC better for peripheral ducts: 87% vs. 63% Comparable inter-observer agreement: 0.83 vs. 0.73 Good diagnostic performance with MRCP Sensitivity 86% Specificity 94% MRC allows access to occluded or isolated ductal segments MRC is the optimal cost-effective approach
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Endoscopic diagnosis of PSC: MRC as standard *Except in early-stage PSC restricted to intrahepatic bile ducts and rare cases of contraindication to MRC ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 MRC has replaced ERCP as the standard in diagnosing PSC* Confirms PSC in patients with high pre-test probability Excludes PSC in patients with low pre-test probability Confirmatory ERCP not required with clinical and biochemical indicators of PSC Unless therapeutic procedures or ductal sampling are indicated Unless findings are ambiguous
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Differential diagnosis of PSC ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Ductographic features defining PSC may be present in other diseases Specificity of cholangiographic features of PSC without the additional diagnostic clinical and biochemical clues is poor
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Endoscopic diagnosis of PSC: Role of ERCP 1. Cesare Hassan, personal communication ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 ERCP may be warranted in some patients with normal MRC Consider level of persisting clinical suspicion Consider impact of diagnosis on patient management and prognosis MRC may miss PSC changes1 Minute calibre ducts disappear Discreet changes disappear with lower resolution Fluid dilation may be necessary In patients with early PSC
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Ductographic criteria for PSC ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Amsterdam criteria classify ductographic changes on cholangiography according to severity Shown to correlate with prognosis
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Ductographic criteria for PSC ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 None of the ductographic criteria are specific for PSC Interpret in the context of demographic data and clinical features Review by teams with expertise in complex biliary disease is useful Multiple secondary causes of sclerosing cholangitis must be considered
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Endoscopic diagnosis with ERCP ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 ERCP is the only suggested endoscopic technique for the diagnosis of PSC No role for brush cytology, ductal biopsy, cholangioscopy, or confocal laser endomicroscopy In selected cases with suspected extrahepatic disease and inconclusive MRC findings Endoscopic ultrasound and elastography may add information on common bile duct strictures, wall thickening, and liver fibrosis stage
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ERCP in confirmed PSC: Relevance of dominant strictures 1. Chapman MH, et al. Eur J Gastroenterol Hepatol 2012;24:1051–8; 2. Rudolph G, et al. J Hepatol 2010;53:3137; 3. Rudolph G, et al. J Hepatol 2009;51:149–55; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Dominant strictures associated with: Pruritus, jaundice, recurrent cholangitis1 More advanced histology1 Increased risk of CCA1 Increased risk of biliary, gallbladder and colorectal carcinoma, when associated with IBD2 Reduced OLT-free survival3 Multiple dominant structures can be found in the same patients Strength of recommendation Quality of evidence 73% No dominant stricture (n=74) 25% Dominant stricture (n=97) p=0.011 18 years 0 0.0 0.2 0.4 0.6 0.8 1.0 5 10 15 20 Time after study entry (years) Survival Survival free of liver transplantation3
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ERCP in confirmed PSC: Relevance of dominant strictures 1. Chapman MH, et al. Eur J Gastroenterol Hepatol 2012;24:1051–8; 2. Rudolph G, et al. J Hepatol 2010;53:3137; 3. Rudolph G, et al. J Hepatol 2009;51:149–55; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Dominant strictures associated with: Pruritus, jaundice, recurrent cholangitis1 More advanced histology1 Increased risk of CCA1 Increased risk of biliary, gallbladder and colorectal carcinoma, when associated with IBD2 Reduced OLT-free survival3 Multiple dominant structures can be found in the same patients Strength of recommendation Quality of evidence 73% No dominant stricture (n=74) 25% Dominant stricture (n=97) p=0.011 18 years 0 0.0 0.2 0.4 0.6 0.8 1.0 5 10 15 20 Time after study entry (years) Survival Survival free of liver transplantation3 Clinical and therapeutic decisions regarding endoscopic interventions should not be based on the definition of dominant stricture(s) alone but considered as a compound clinical decision
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ERCP in confirmed PSC: Assessing risk of CCA *Not related to liver failure; †Especially in patients with a diagnosis of clinically significant hilar or extrahepatic strictures on MRC ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 ERCP may be indicated in confirmed PSC and changes in: Clinical events Exacerbation of jaundice* Episodes of fever and chills suggestive of cholangitis Worsening of pruritus Worsening pain in right upper abdominal quadrant, fatigue, and weight loss Laboratory abnormalities Rapid increase in serum bilirubin levels and/or cholestatic liver enzymes† Clinically significant strictures on US or MRC New onset or progressive intrahepatic or extrahepatic bile duct dilatation Strength of recommendation Quality of evidence
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ERCP in confirmed PSC: Assessing risk of CCA ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Disproportionately severe stricture and concomitant biliary filling defects Marked biliary dilatation Common bile duct ≤2 cm Right or left intrahepatic ducts ≤1 cm Other intrahepatic ducts ≤5 mm Abnormal cytological findings Suspicion of malignancy Aneuploid DNA New-onset dominant stricture(s) SUGGESTS CCA ↓ ERCP US/MRC findings
Slide 26-

Therapeutic ERCP in selected patients *Strength of recommendation, weak; quality of evidence, low ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 In patients with confirmed PSC, MRC should be considered prior to therapeutic ERCP to confirm the indication* Exclude focal parenchymal changes Guide clinicians performing the ERCP to minimize the risk of complications Potential benefits must be weighed against known risks in patients with no other therapeutic option except LTx Following dominant stricture treatment: In patients with a significant (≤20%) increase in cholestasis, cholestasis, pruritus, pain, cholangitis, and jaundice are likely to improve In patients with ESLD, only cholangitis is expected to improve Strength of recommendation Quality of evidence
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Therapeutic ERCP: Overall outcomes Stiehl A, et al. J Hepatol 2002;51:151–6 106 patients treated for up to 13 years with UDCA 57 with dominant strictures treated endoscopically 52 repeated balloon dilations 5 temporary stenting KM survival rates free of LTx 5 years after first dilation Stage 2: 100% Stage 3: 72% Stage 4: 50% Overall survival improved vs. Mayo prognostic model (p<0.001) Stage 1 and Stage 2 vs. Stage 3: p<0.01 Stage 1 and Stage 2 vs. Stage 4: p<0.001 Stage 1 Stage 2 Stage 3 Stage 4 Overall 0 0.0 0.4 0.6 0.8 1.0 20 40 60 80 Time after study entry (months) Survival Survival free of liver transplantation 106 93 67 48 26 0.2 100 7 120 3 140 160 N=
Slide 28-

Balloon dilation vs. balloon dilation + stenting *2 weeks 1. Ponsioen C, et al. J Hepatol 2017;66:S1–2; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Data are largely limited to retrospective studies: Significant improvement in LTx-free survival compared with the Mayo model has been reported only with balloon dilation Reported perforation rate is generally higher with stenting vs. balloon dilation Rates of SAEs are higher with stenting vs. balloon dilation DILSTENT trial comparing single balloon dilation vs. short-term* stenting was prematurely stopped1 No differences in recurrence-free re-intervention rates or initial failure Significantly higher SAE rate, mainly post-ERCP pancreatitis and suppurative cholangitis, was seen in the stent group (42%) vs. balloon group (10%)
Slide 29-

Balloon dilation vs. balloon dilation + stenting *S, stent; BS, balloon dilation + stent; B, balloon dilation; †LTx-free survival; ‡52% laboratory improvement/70% clinical improvement; §Mean References are in notes ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Data are largely limited to retrospective studies
Slide 30-

Balloon dilation vs. balloon dilation + stenting *S, stent; BS, balloon dilation + stent; B, balloon dilation; †LTx-free survival; ‡52% laboratory improvement/70% clinical improvement; §Mean; ‖Strength of recommendation, weak; quality of evidence, low References are in notes ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Data are largely limited to retrospective studies
Slide 31-

Therapeutic ERCP: Role of sphincterotomy ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Biliary sphincterotomy is not recommended routinely prior to biliary stenting If cannulation is difficult, biliary sphincterotomy is advised These patients are likely to require multiple procedures
Slide 32-

Therapeutic ERCP: Dilation schemes *Complete balloon inflation within the dominant stricture with no waist observed fluoroscopically, followed by the unobstructed passage of contrast medium through the dilated biliary segment to the duodenum ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 No comparative data on optimal dilation scheme or balloon diameter Consider bile duct diameter upstream and downstream of the dominant stricture to avoid dilating to more than the duct diameter Balloon dilations are usually repeated at intervals of 14 weeks Until technical success* For an average of 2–3 balloon dilations
Slide 33-

Therapeutic ERCP: Stent therapy *Final stent diameter in the case of stepwise stenting 1. Cesare Hassan, personal communication ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Plastic stents only should be used1 Stent calibre and length should be adapted to the specific biliary tree configuration Need for pre-stent balloon dilation is unclear Short-term stenting duration is favoured Stents tend to clog rapidly in PSC patients Similar efficacy with stenting for 1–2 weeks vs. 8–12 weeks
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Therapeutic ERCP: Complications ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 ERCP carries an increased risk of complications in the context of PSC Pancreatitis in up to 7% of procedures NSAIDs and prophylactic pancreatic stenting are beneficial Cholangitis in up to 8% of procedures Suggest that cannulation in patients with PSC may be more difficult than in other patients
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Therapeutic ERCP: Risk of pancreatitis ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 High risk for post-ERCP pancreatitis Pre-cut biliary sphincterotomy Pancreatic guidewire-assisted biliary cannulation Endoscopic balloon sphincteroplasty Pancreatic sphincterotomy Plus > 3 of: Female gender Previous pancreatitis Younger age Non-dilated extrahepatic bile ducts Absence of chronic pancreatitis Normal serum bilirubin, Duration of cannulation attempts >10 minutes >1 pancreatic guidewire passage Pancreatic injection Failure to clear bile duct stones Intraductal ultrasound
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Therapeutic ERCP: Bacterial cholangitis ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Bacterial cholangitis and bacteriobilia are relatively common in PSC Use of prophylactic antibiotics are beneficial in elective ERCP Reduce bacteraemia Seem to prevent cholangitis and septicaemia Bile fluid sampling could be considered during ERCP Guide antibiotic treatment if cholangitis occurs despite prophylaxis Strength of recommendation Quality of evidence
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ERCP in confirmed PSC: Assessing risk of CCA ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Disproportionately severe stricture and concomitant biliary filling defects Marked biliary dilatation Common bile duct ≤2 cm Right or left intrahepatic ducts ≤1 cm Other intrahepatic ducts ≤5 mm Abnormal cytological findings Suspicion of malignancy Aneuploid DNA New-onset dominant stricture(s) SUGGESTS CCA ↓ ERCP US/MRC findings
Slide 38-

PSC and cholangiocarcinoma *Particularly with an associated enhancing mass lesion 1. Dyson JK, et al. Lancet 2018; http://dx.doi.org/10.1016/S0140-6736(18)30300-3; 2. Boonstra K, et al. Hepatology 2013;58:2045–55; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Cancer screening is a key part of follow-up1 Lifetime risk for CCA in patients with PSC is 10–20% Up to 400-fold higher than general population CCA is a common cause of death among patients with PSC In a large Dutch study:2 CCA in 41/590 (7%) patients 33/41 died (80%) after a median period of 1 year (range, 0–7)2 Strength of recommendation Quality of evidence
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Brush cytology for identification of CCA 1. Boberg KM, et al. J Hepatol 2006;45:568–74; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Bile duct brushing is highly specific for CCA Sensitivity is modest Precludes utility for early detection of CCA in PSC Addition of FISH analysis enhances the sensitivity for detecting CCA Ductal biopsy improves sensitivity, specificity, and accuracy Other techniques are not established in routine clinical practice Brush cytology specimens showing low- and high-grade dysplasia1 Low High Corresponding bile duct histology1
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ERCP findings alone cannot exclude CCA ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Not possible to distinguish malignant and benign strictures with ERCP alone Diagnosis always requires additional techniques Most CCAs develop in the perihilar region or in extrahepatic bile ducts Reachable with a cytological brush Strength of recommendation Quality of evidence
Slide 41-

Endoscopic surveillance of PSC-associated IBD 1. Claessen MM, et al. J Hepatol 2009;50:158–64; ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Relationship between PSC and IBD is well-established Risk of CRC is higher in patients with PSC + IBD than PSC alone1 Long-term risk of CRC in PSC + IBD patients is about threefold higher than risk of CCA1 Occurrence of CRC in these patients leads to reduced survival1 2% Without IBD 31% With IBD p=0.008 20 years 0 0 20 30 40 50 5 Time (years) Cumulative risk (%) Cumulative risk of CRC in 211 patients with PSC1 56 10 Number at risk: 75 10 33 43 15 10 23 20 3 4 25 1 0 85 114 Without IBD With IBD
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Endoscopic surveillance of PSC-associated IBD ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Risk of CRC in PSC-associated IBD makes it crucial to perform a full ileocolonoscopy at the time of PSC diagnosis in all patients Follow-up based on findings Endoscopic surveillance of PSC-associated colitis is presumed to increase the chance of early detection of dysplasia or malignancy Strength of recommendation Quality of evidence
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Endoscopic surveillance of PSC-associated IBD ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Most dysplasia is visible at colonoscopy Invisible dysplastic lesions be diagnosed by random biopsies during surveillance Strength of recommendation Quality of evidence
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Summary
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Main recommendations ESGE/EASL CPG Endoscopy in PSC. J Hepatol 2017;66:1265–81 Strength of recommendation Quality of evidence