9/14/2018 Disclosures Consultant for Boston Scientific and Olympus - - PDF document

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9/14/2018 Disclosures Consultant for Boston Scientific and Olympus - - PDF document

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9/14/2018 Disclosures Consultant for Boston Scientific and Olympus Early Allograft Dysfunction and Biliary No off-label use of devices and equipment Strictures After Liver Transplantation Mustafa Arain, MD Associate Professor of Medicine

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Early Allograft Dysfunction and Biliary Strictures After Liver Transplantation

Mustafa Arain, MD Associate Professor of Medicine Director of Advanced Endoscopy University of California – San Francisco mustafa.arain@ucsf.edu

Disclosures

Consultant for Boston Scientific and Olympus No off-label use of devices and equipment

Outline

  • Indications and anatomic considerations
  • Diagnostic evaluation
  • Endoscopic interventions
  • Living donor liver transplant (LDLT)

Indications- Biliary Complications Strictures Leaks Stones

Early - Days Early – Occasionally Late – Weeks to Years Late – Months to Years

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ERCP for elevated LFTs and suspected anastomotic stricture

? Stricture Air in the biliary tree

Patient with a Roux-en-Y Hepatico-jejunosotomy

Anatomic Considerations

  • Ductal anatomy
  • Type of surgery – type of liver donation
  • Understanding of segmental and sectoral anatomy

Ductal Anatomy

Choledocho- dochal anastomosis

  • Aka duct to duct (DD)

anastomosis

  • Most common
  • Easy endoscopic access
  • Availability of a wide

selection of accessories and stents

Donor duct Recipient duct Anastomosis (with stricture)

Ductal Anatomy

Roux-en-Y hepatico- jejunostomy

  • Enteroscopy assisted

ERCP

  • Need to reach jejuno-

jejunal anastomosis and then advance the scope up the biliary limb

  • Limited accessories
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Donor variation

Complete

  • Deceased donor liver (DD)
  • Donor after cardiac death

(DCD)

  • Increased risk of biliary

complications vs DD

Partial Liver

  • Living donor transplant

(LDLT)

  • Right lobe
  • Smaller duct caliber –

increased complications vs DD

  • Split liver transplant (SLD)
  • Left or right lobe

Sectoral Ductal Anatomy

Left hepatic duct sector

  • II, III and IV

Right anterior sector

  • V and VIII

Right posterior sector

  • VI and VII

Diagnosis

 Clinical suspicion early post-operatively  Asymptomatic – incidental finding on routine labs/imaging  Symptoms – pain, fever, jaundice, pruritis  Labs

 Elevated LFTs  Signs of infection

Imaging Modalities

  • Ultrasound
  • Nuclear medicine scan
  • CT
  • MRCP
  • EUS
  • ERCP
  • PTC

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

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Imaging Modalities

  • Ultrasound
  • Nuclear medicine scan
  • CT
  • MRCP
  • EUS
  • ERCP
  • PTC

Ductal dilation on US, Doppler for vascular abnormalities

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

Imaging Modalities

  • Ultrasound
  • Nuclear medicine scan
  • CT
  • MRCP
  • EUS
  • ERCP
  • PTC

Biliary leak evaluation

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

Nuclear Medicine Hepatobiliary Scan

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Surgical Drain Surgical Drain

Nuclear Medicine Hepatobiliary Scan

Surgical Drain

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Imaging Modalities

  • Ultrasound
  • Nuclear medicine scan
  • CT
  • MRCP
  • EUS
  • ERCP
  • PTC

Fluid collections/ abscesses

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

Imaging Modalities

  • Ultrasound
  • Nuclear medicine scan
  • CT
  • MRCP
  • EUS
  • ERCP
  • PTC

Main diagnostic study

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

MRCP (Magnetic Resonance Cholangiopancreatograpy)

  • Non-invasive, non-contrast
  • Evaluation of entire biliary tree
  • Provides a roadmap of anatomy prior to intervention
  • High sensitivity for determining strictures and stones
  • Newer contrast media allows dynamic imaging of the biliary system

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

MRCP

Limitations

  • Pacemaker/ICD
  • Patient compliance, claustrophobia
  • Small stones may be missed
  • May falsely suggest stricture at anastomotic site
  • Contrast MRI
  • Nephrogenic systemic sclerosis

Yeh BM et al. Radiographics 2009, Seale MK et al. Radiographics 2009, Boraschi P et al. Clin Transplant 2010, Beltran MM et al. Transplant Proc 2005

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MRCP: Anastomotic stricture in LDLT

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Imaging Modalities

  • Ultrasound
  • Nuclear medicine scan
  • CT
  • MRCP
  • EUS
  • ERCP
  • PTC

Rarely done early, can be done to evaluate biliary/pancreatic diseases

Imaging Modalities

  • Ultrasound
  • Nuclear medicine scan
  • CT
  • MRCP
  • EUS
  • ERCP
  • PTC

Therapeutic procedures, should NOT be considered diagnostic studies

Biliary Strictures

Anastomotic

  • Short, focal stricture, at the bile

duct anastomosis

  • Occur in 5-10 % of patients with

deceased donor transplantation

  • Scarring and fibrosis

Non-anastomotic strictures

  • Upstream from biliary anastomosis,

involve intrahepatic ducts/branches

  • Deceased Donor: 5-15%, Donor

after cardiac death: 20-33%

  • Multiple etiologies
  • Ischemia plays a major role
  • Associated with HA

stenosis/occlusion, PV occlusion, CMV, PSC, ABO incompatibility, chronic rejection

Arain MA et al. Liver Transpl 19:482–498, 2013, Koneru B. Liver Transpl 2006;12:702-704 Duffy JP et al. Ann Surg 2010;252:652-661, Ayoub WS et al. Dig Dis Sci 2010;55: 1540-1546

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Biliary Strictures

Anastomotic

  • Respond well to endoscopic

therapy

Non-anastomotic strictures

  • Difficult to treat
  • Require prolonged treatment often

12 months or more with multiple endoscopic procedures

  • Increased morbidity, decreased

graft survival

Arain MA et al. Liver Transpl 2013, Koneru B. Liver Transpl 2006, Buxbaum JL et al GIE 2011 Duffy JP et al. Ann Surg 2010, Ayoub WS et al. Dig Dis Sci 2010

Anastomotic Stricture on MRCP ERCP Balloon dilation of the stricture

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Multiple stents across the stricture High grade Anastomotic Stricture

No filling above the stricture initially Wire passage across the stricture

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Proximal filling Balloon Dilation Fully covered metal biliary stent

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Resolution

Principles of Stricture Management

  • Sphincterotomy → Balloon dilation → Stent placement
  • Repeat ERCP q2-3 months and place maximal number of large

caliber stents (10 Fr) until stricture resolves

  • Consider fully covered metallic biliary stents for high grade,

resistant strictures or as first line therapy - associated with fewer number of procedures* (two recent randomized trials)

Graziadei IW et al. Liver Transpl 2006, Rizk RS et al. Gastrointest Endosc 1998, Morelli J et al. Gastrointest Endosc 2003, Costamagna G et al. Gastrointest Endosc 2001, *Cote G et al. JAMA 2016, *Tal AO et al. GIE 2017

ERCP early post-op, low platelets

Pancreatic duct cannulation CBD stricture Pancreatic duct stent

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Balloon dilation

  • f the biliary
  • rifice

Biliary stents Pancreatic stent

Difficult Stricture: PTC aided treatment Percutaneous transhepatic balloon dilation

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Percutaneous transhepatic balloon dilation Non-anastomotic Strictures Filling of all three sectoral ducts

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Balloon dilation: Right posterior hepatic duct Balloon dilation: Right anterior hepatic duct Balloon dilation: left hepatic duct 10 Fr stents in all sectoral ducts

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Ischemic Cholangiopathy – 3 mo post Ischemic Cholangiopathy – 3 mo post Ischemic Cholangiopathy – 3 mo post Ischemic Cholangiopathy – 3 mo post

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‘Resolution’ after 8 ERCPs… DCD complicated by HA stenosis MRCP – Ischemic cholangiopathy

Central scarring extending into the intrahepatic branches No specific target for endoscopic therapy

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Post-transplant Bile Leaks

  • Up to 25% of patients
  • Etiology
  • Anastomotic site leak
  • Ischemic injury
  • T-tube insertion (if done)
  • Surface leak
  • Associated with fluid collections, abscesses
  • Generally, respond to intensive endoscopic therapy
  • however, high rate of PTC and surgery reported in the literature

Arain MA et al. Liver Transpl 19:482–498, 2013, Koneru B. Liver Transpl 2006;12:702-704 Duffy JP et al. Ann Surg 2010;252:652-661, Ayoub WS et al. Dig Dis Sci 2010;55: 1540-1546

Bile leak – Duct to duct anastomosis

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Bile leak – Duct to duct anastomosis

Pancreatic wire Percutaneous drain CBD

Bile leak – Duct to duct anastomosis

Anastomotic leak

Bile leak – Duct to duct anastomosis

CBD and PD stents

Biliary Leak

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Principles of Anastomotic Leak Management

  • Sphincterotomy (assuming no contraindication) → Avoid balloon

dilation → Stent placement across the leak

  • Repeat ERCP in 4-6 weeks and upsize stent(s) and/or place

additional stents (if possible)

  • May develop stricture at the leak site – dilation okay once leak

resolves

Graziadei IW et al. Liver Transpl 2006, Rizk RS et al. Gastrointest Endosc 1998, Morelli J et al. Gastrointest Endosc 2003, Costamagna G et al. Gastrointest Endosc 2001

Stones and Casts

  • Bile Stasis

Stone formation

  • Biliary strictures lead to stasis … there similar risk factors for stone

formation as strictures (arterial/venous compromise, ischemia etc)

  • NAS

Recurrent intrahepatic stones/casts

  • Casts syndrome – multiple large, hard stones, often hilar/central

ductal dilation, longstanding impairment of flow vs different etiology?

Stones on MRCP

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Biliary Casts Endoscopy in Altered anatomy

Roux-en-Y hepaticojejunostomy (RYHJ)

  • Enteroscopy assisted ERC
  • Pediatric colonoscope
  • Device assisted (single balloon or double balloon enteroscopy)

Roux-en-Y gastric bypass (RYGB)

  • Enteroscopy
  • Remnant access
  • Percutaneous, EUS-guided or surgical access
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Deep Enteroscopy : Single balloon overtube assisted Stenotic anastomosis Cannulation

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Balloon dilation Living Donor Liver Transplantation

  • Difficult anastomoses due to small size of donor ducts
  • Higher incidence of ischemic and non-ischemic complications
  • A2ALL – multi-center US cohort
  • Recipient: Leak 32%, Stricture 17%
  • Donor: Leak 9.2%, Stricture 0.7%

Olthoff KM et al. Ann Surg 2005, Ghobrial RM et al. Gastroenterology 2008, Soejima Y et al. Liver Transpl 2006, Seo JK et al. Liver Transpl 2009

Living Donor Liver Transplantation

  • Management
  • Biliary strictures – Response 60-80%...low
  • Biliary leaks – Need for surgery 50-65%...high
  • High rates of PTC and surgery for both…really necessary?

Olthoff KM et al. Ann Surg 2005, Ghobrial RM et al. Gastroenterology 2008, Soejima Y et al. Liver Transpl 2006, Seo JK et al. Liver Transpl 2009, Rao HB et al WJG 2018

MRCP:Anastomotic stricture in LDLT

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Right anterior and posterior sectoral access Balloon dilation Bisectoral stent placement

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Follow-up ERCP Additional stent placement into right anterior duct Resolution of strictures LDLT with early anastomotic leak

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Small intrahepatic ducts Bisectoral access Bisectoral 5 Fr stents Follow-up ERCP

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7 Fr and 8.5 Fr stents Resolution of leak Leak with fistula and abscess Gastric fistula to the abscess cavity

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Balloon dilation of fistula tract and transpapillary stent into the abscess

Cavity sweep/lavage with a stone retrieval balloon Multiple stents

Transgastric stent into cavity Transpapillary stent into cavity Transpapillary biliary stent

Resolution (months later)

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LDLT leak – Anastomotic variation

Cystic duct to right posterior Hepatic duct to right anterior

Right anterior duct anastomotic leak

Cystic duct to right posterior Hepatic duct to right anterior Leak

Dual stents Resolution of leak

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Right LDLT with RYHJ Enteroscopy ERC Right LDLT

Anterior duct wire Posterior duct wire

Stents after balloon dilation

Anterior duct stent Posterior duct stent

Donor Leak

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Dual stents – 10 Fr long and short

Resolution of leak

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Complication Recurrence

  • 13/46 (28%) pts
  • All were biliary strictures
  • Median duration from stent removal to presentation: 3.7 months (0.7-19.3)
  • 12/13 treated with repeat ERCP
  • Median # of ERCPs: 4 (range 2-9)
  • No PTC or surgery
  • 1 pt lost to follow-up

Advances in ERCP Technology

  • Access
  • SwingTip, bidirectional, steerable cannula
  • Wide array of wires (Visiglide, NovaGold, Terumo Glide)
  • Therapy
  • Soft large caliber stents (Johlin)
  • Covered metal biliary stents
  • Cholangioscopy
  • Direct using a pediatric endoscope
  • SpyGlass -> SpyGlass DS (fiber optic vs digital)

Conclusions

  • Biliary complications are common post LT
  • Non-invasive diagnostic imaging (MRCP, HIDA) should

precede therapeutic endoscopy

  • Advanced endoscopists must be knowledgeable in biliary

anatomy and be aware of the patient’s type of transplant and ductal anatomy

  • Advances in endoscopic technologies and development of

newer accessories allow a high proportion (ideally over 90%)

  • f patients to be treated endoscopically
  • Duration of therapy varies depending on underlying etiology

e.g. type of donor liver, vascular complications etc.

  • Patients require a multi-disciplinary approach to co-manage

complications (e.g. leaks) and/or facilitate endoscopic treatment (e.g. difficult access)

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