Endoscopic management of bile duct cancers

1. ENDOSCOPIC DIAGNOSIS AND
MANAGEMENT OF BILE DUCT
CANCERS
Jason Klapman, M.D.Jason Klapman, M.D.
Associate Professor of MedicineAssociate Professor of Medicine
Director of EndoscopyDirector of Endoscopy
Gastrointestinal Tumor ProgramGastrointestinal Tumor Program
Moffitt Cancer CenterMoffitt Cancer Center

2. Outline
 Pre-Procedure EvaluationPre-Procedure Evaluation
 Imaging studiesImaging studies
 Determine ResectabilityDetermine Resectability
 Tissue DiagnosisTissue Diagnosis
 ERCP-cyto/biopsiesERCP-cyto/biopsies
 EUS with Fine Needle AspirationEUS with Fine Needle Aspiration
 Cholangioscopic directed biopsiesCholangioscopic directed biopsies
 Endoscopic TreatmentEndoscopic Treatment
 StentingStenting
 Endoscopic directed therapyEndoscopic directed therapy

3. Bismuth Classification
 Type 1 (Extrahepatic)Type 1 (Extrahepatic)
 25%25%
 Type II-IVType II-IV
 Klatskin’s TumorsKlatskin’s Tumors
60-65%60-65%
 Intrahepatic CCAIntrahepatic CCA
10-15%10-15%

4. Klatskin’s Tumor
 Definition- Perihilar tumors that involve the- Perihilar tumors that involve the
bifurcation of the hepatic ductbifurcation of the hepatic duct
 Represent 60-65% of all CCARepresent 60-65% of all CCA
 5-year survival 15-30%5-year survival 15-30%
 Resectable in only 30%Resectable in only 30%
 Palliation mainstay of treatmentPalliation mainstay of treatment

5. Criteria For Unresectability
 Medical contraindications to surgeryMedical contraindications to surgery
 N2 nodal disease or distant liver metastasesN2 nodal disease or distant liver metastases
 Vascular invasionVascular invasion
 Extra-hepatic adjacent organ invasionExtra-hepatic adjacent organ invasion
 Presence of disseminated diseasePresence of disseminated disease
 LOCAL UNRESECTABILITYLOCAL UNRESECTABILITY

6. Local Unresectability
 Involvement of bilateral hepatic duct up toInvolvement of bilateral hepatic duct up to
secondary radicles bilaterally, encasement/secondary radicles bilaterally, encasement/
occlusion or PV/ HAocclusion or PV/ HA
 Determined by Imaging studiesDetermined by Imaging studies
CTscan, MRI/MRCP, ERCP and EUSCTscan, MRI/MRCP, ERCP and EUS
 Surgical ExplorationSurgical Exploration

7. Klatskin’s Tumor

8. Labs
Imaging
Resectable?
ERCP
Work-up
MRCP

9. Magnetic Resonance Cholangio-
Pancreatography (MCRP)
 Non-invasiveNon-invasive
 Detailed imaging of biliary systemDetailed imaging of biliary system
 Roadmap for EndoscopistRoadmap for Endoscopist
Targets therapyTargets therapy
Optimizes TreatmentOptimizes Treatment
Minimizes complicationsMinimizes complications
• CholangitisCholangitis

10. ERCP
MRCP

11. MRCP
 TARGETING THERAPYTARGETING THERAPY
 Hintze et al GIE 2001
Evaluated MRCP to aid in unilateral stentEvaluated MRCP to aid in unilateral stent
placement for Klatskin’s Tumor’splacement for Klatskin’s Tumor’s
Resolution of Bilirubin in 86%Resolution of Bilirubin in 86%
Cholangitis 2/35Cholangitis 2/35
 Freeman GIE 2003Freeman GIE 2003
CT scan or MRCP to selectively targetCT scan or MRCP to selectively target
drainage using metallic stentsdrainage using metallic stents
Palliation in 77% of patientsPalliation in 77% of patients

12. Labs
Imaging
Resectable?
ERCP
Traditional Work-up
MRCP
StentDX

13. Tissue Sampling by ERCP
 Brush CytologyBrush Cytology
 Forceps BiopsyForceps Biopsy

14. Brush Cytology in Malignant
Biliary Strictures
AuthorsAuthors YRYR PT’sPT’s Ca.Ca. TPTP SeSe SpeSpe PPVPPV NPVNPV
Foutch et alFoutch et al 9191 3030 1717 66 33%33% 100%100% 100%100% 58%58%
Lee et alLee et al 9595 149149 106106 4040 37%37% 100%100% 100%100% 39%39%
Ponchon et alPonchon et al 9595 204204 127127 4545 35%35% 97%97% 96%96% 44%44%
Pugliese et alPugliese et al 9595 9494 6464 3535 54%54% 100%100% 100%100% 50%50%
Glasbrenner et alGlasbrenner et al 9999 7878 5757 3232 56%56% 90%90% 84%84% 43%43%
Mansfield et alMansfield et al 9797 4343 4141 1717 42%42% 100%100% 100%100% 8%8%
Jailwala et alJailwala et al 9999 133133 104104 3131 30%30% 100%100% 100%100% 28%28%
Macken et alMacken et al 0000 106106 6262 3535 57%57% 100%100% 100%100% 62%62%
TotalTotal 837837 578578 241241 42%42% 98%98% 99%99% 43%43%
De bellis et al, GIE 2002

15. ERCP-guided Biopsy of
Malignant Biliary Strictures
AuthorsAuthors YRYR PT’sPT’s Ca.Ca. TPTP SeSe SpeSpe PPVPPV NPVNPV
Kubota et alKubota et al 9292 4141 3232 2626 81%81% 100%100% 100%100% 75%75%
Pugliese et alPugliese et al 9494 5252 3636 1919 53%53% 100%100% 100%100% 48%48%
Ponchon et alPonchon et al 9595 128128 8282 3535 43%43% 97%97% 97%97% 41%41%
Sugiyama et alSugiyama et al 9696 4545 3131 2525 81%81% 100%100% 100%100% 67%67%
Schoefl et alSchoefl et al 9797 103103 5858 3838 65%65% 100%100% 100%100% 69%69%
Jailwala et alJailwala et al 9999 133133 104104 4848 43%43% 90%90% 94%94% 31%31%
TotalTotal 502502 343343 191191 56%56% 97%97% 97%97% 51%51%
De bellis et al, GIE 2002

16. Combined Brush and Biopsy of
Malignant Biliary strictures
AuthorsAuthors YRYR BrushBrush BiopsyBiopsy Brush andBrush and
BiopsyBiopsy
Ponchon et alPonchon et al 9595 33%33% 44%44% 61%61%
Pugliese et alPugliese et al 9595 54%54% 55%55% 61%61%
Schoefl et alSchoefl et al 9797 47%47% 65%65% 70%70%
De bellis et al, GIE 2002

17. EUS-guided FNA
 Useful in obtaining a diagnosis in pt’s withUseful in obtaining a diagnosis in pt’s with
negative ERCP cytology and high index ofnegative ERCP cytology and high index of
suspicionsuspicion
 Fritscher-Ravens et al.Fritscher-Ravens et al. GIE 2000GIE 2000
9/10 with Hilar lesions obtained a Tissue9/10 with Hilar lesions obtained a Tissue
DiagnosisDiagnosis
2 patients had LN’s aspirated2 patients had LN’s aspirated
 Eloubeidi et al.Eloubeidi et al. Clin Gastro and Hepatol 2004Clin Gastro and Hepatol 2004
25/28 pts underwent FNA25/28 pts underwent FNA
• 18 CCA, 4 benign and 3 FN18 CCA, 4 benign and 3 FN
• Impacted Pt management in 84%Impacted Pt management in 84%

18. EUS-guided FNA

19. EUS-guided FNA

20. Cholangioscopy with biopsies
 Single-operator system introduced in 2005Single-operator system introduced in 2005
 Indeterminate biliary stricturesIndeterminate biliary strictures
 Ramchandani et al. GIE 2011Ramchandani et al. GIE 2011
 36pts (22 malignant) underwent36pts (22 malignant) underwent
cholangioscopy with biopsiescholangioscopy with biopsies
Accuracy was 89% for differentiatingAccuracy was 89% for differentiating
malignant vs. non-malignant stricturesmalignant vs. non-malignant strictures
Accuracy in pt’s with previous inconclusiveAccuracy in pt’s with previous inconclusive
ERCP brushings or biopsies was 82%ERCP brushings or biopsies was 82%

21. Cholangioscopy with biopsies
 Draganov et al. GIE 2012Draganov et al. GIE 2012
Compared conventional cytologyCompared conventional cytology
brushings and biopsies andbrushings and biopsies and
cholangioscopic biopsies on 26cholangioscopic biopsies on 26
patients (17 cancer)patients (17 cancer)
Cholangioscopic biopsies significantlyCholangioscopic biopsies significantly
higher accuracy (84.6% vs. 58% vs.higher accuracy (84.6% vs. 58% vs.
38.5 %)38.5 %)

22. Diagnostic algorithm for tissue
diagnosis
 ERCP brushings/biopsy- if negativeERCP brushings/biopsy- if negative
 EUS with FNA- if negativeEUS with FNA- if negative
 ERCP with cholangioscopic guidedERCP with cholangioscopic guided
biopsies-if negative??biopsies-if negative??
 DDx- benign vs. malignantDDx- benign vs. malignant
Consider repeat ERCP withConsider repeat ERCP with
cholangioscopic biopsies if mass ischolangioscopic biopsies if mass is
seen and clinical suspicion highseen and clinical suspicion high

23. Endoscopic Palliation
 StentingStenting
 Unilateral vs. Bilateral?Unilateral vs. Bilateral?
 Plastic vs. Metallic?Plastic vs. Metallic?

24. Are two stents better than one to
obtain resolution of jaundice?
 Technical issuesTechnical issues
 Feasibility of placing 2 stentsFeasibility of placing 2 stents
 Risk of cholangitis of undrained biliaryRisk of cholangitis of undrained biliary
segment if unable to place 2 stentssegment if unable to place 2 stents
 MRCP useful to target drainageMRCP useful to target drainage
R hepatic duct 1cmR hepatic duct 1cm
L hepatic duct 3cmL hepatic duct 3cm
 Drainage of 25% of liver resolves jaundiceDrainage of 25% of liver resolves jaundice
 L lobe-35%, R-lobe-55-60%, caudate lobe 10-L lobe-35%, R-lobe-55-60%, caudate lobe 10-
15%15%

25. Unilateral vs. Bilateral Stenting
 Chang et al., GIE 1998Chang et al., GIE 1998
 Evaluated the outcomes of 98 patients withEvaluated the outcomes of 98 patients with
unresectable CCA who underwent unilateral orunresectable CCA who underwent unilateral or
bilateral stentingbilateral stenting
Retrospective reviewRetrospective review
Patients with bilateral drainage had aPatients with bilateral drainage had a
significant survival advantage 225 vs. 80significant survival advantage 225 vs. 80
daysdays
Cholangitis 11% (32% in pts with un-Cholangitis 11% (32% in pts with un-
drained segments)drained segments)

26. Unilateral vs. Bilateral Stenting
 De Palma et al. GIE 2001De Palma et al. GIE 2001
 Compared unilateral vs. bilateral hepatic ductCompared unilateral vs. bilateral hepatic duct
drainagedrainage
 157 patients randomly assigned prospectively157 patients randomly assigned prospectively
 Unilateral group had higher stent insertionUnilateral group had higher stent insertion
success and less complicationssuccess and less complications
 Successful drainage, survival comparable inSuccessful drainage, survival comparable in
both groupsboth groups
 ConclusionConclusion:bilateral stenting not justified and may:bilateral stenting not justified and may
increase complicationsincrease complications

27. Unilateral vs. Bilateral Stenting
 De Palma et al. GIE 2003De Palma et al. GIE 2003
 Evaluated Unilateral metal stent placement forEvaluated Unilateral metal stent placement for
hilar obstruction in 61patientshilar obstruction in 61patients
 All patients underwent MRCP pre-procedureAll patients underwent MRCP pre-procedure
Stent insertion 59/61Stent insertion 59/61
Successful biliary drainage in 59/61Successful biliary drainage in 59/61
Cholangitis 5%Cholangitis 5%
Median stent patency of 169 daysMedian stent patency of 169 days

28. Unilateral vs. Bilateral Stenting
 Naitoh et al. J Gastroenterol Hep 2009Naitoh et al. J Gastroenterol Hep 2009
 Retrospective series of 46 patientsRetrospective series of 46 patients
showed better outcomes with bilateral vs.showed better outcomes with bilateral vs.
unilateral stentingunilateral stenting
Improved stent patency bilateral groupImproved stent patency bilateral group
488 vs. 210 days for unilateral group488 vs. 210 days for unilateral group
(p=.009)(p=.009)

29. Endoscopic Palliation
PLASTIC vs. METAL?PLASTIC vs. METAL?

30. Plastic Stents Metal Stents
 Median Patency 3-Median Patency 3-
5mos5mos
 Average diameter isAverage diameter is
10Fr (3.3mm)10Fr (3.3mm)
 Stent change q3mos.Stent change q3mos.
 Median Patency 6-Median Patency 6-
8mos8mos
 Self expandable up toSelf expandable up to
30Fr (10mm)30Fr (10mm)
 PermanentPermanent

31. Plastic vs. Metal?
 Life ExpectancyLife Expectancy
 Quality of LifeQuality of Life
 CostCost
 Physician ExpertisePhysician Expertise
No Difference in Survival

32. ERCP Complications
 ImmediateImmediate
 CholangitisCholangitis
Antibiotics pre/post procedureAntibiotics pre/post procedure
Selective Opacification during ERCPSelective Opacification during ERCP
 PancreatitisPancreatitis
 BleedingBleeding
 LateLate
 Stent OcclusionStent Occlusion

33. New technology
 Cook Zilver635Cook Zilver635®® systemsystem
 UUncovered metal stent deployment system that uses ancovered metal stent deployment system that uses a
6fr deliver catheter6fr deliver catheter
 Sizes 6,8 and 10mm and 4,6 and 8cm lengthSizes 6,8 and 10mm and 4,6 and 8cm length
 Advantages over conventional SEMSAdvantages over conventional SEMS
 Less need to dilate Hilar strictures as the introducerLess need to dilate Hilar strictures as the introducer
system is much smallersystem is much smaller
 Allows simultaneous deployment of bilateral stentsAllows simultaneous deployment of bilateral stents
through the scopethrough the scope
• This allows easier access in the future to eachThis allows easier access in the future to each
side of the biliary system as they are side by sideside of the biliary system as they are side by side
and not in the Y configurationand not in the Y configuration

34. Zilver635® 6F system
 Waxman et al. GIE 2010Waxman et al. GIE 2010
 49 stents placed in 16 patients49 stents placed in 16 patients
 Technical success was 100%Technical success was 100%
 Side by Side deployment achieved in all 10Side by Side deployment achieved in all 10
cases attemptedcases attempted
 Additional transpapillary stenting wasAdditional transpapillary stenting was
performed for future accessperformed for future access
 Conclusion- works great but would like longerConclusion- works great but would like longer
lengths that may bridge papillalengths that may bridge papilla

37. Simultaneous deployment video

38. Tips and tricks for deployment
 Spray Pam for lubricationSpray Pam for lubrication
 Consider a small sphincterotomyConsider a small sphincterotomy
 Although different sizes exist, try and placeAlthough different sizes exist, try and place
largest diameter stent when possiblelargest diameter stent when possible
 When stents unable to bridge papilla,When stents unable to bridge papilla,
consider deploying shorter 2consider deploying shorter 2ndnd
stents withinstents within
stents to allow for future access for re-stents to allow for future access for re-
interventionintervention

39. Outline
 Pre-Procedure EvaluationPre-Procedure Evaluation
 Imaging studiesImaging studies
 Determine ResectabilityDetermine Resectability
 Tissue DiagnosisTissue Diagnosis
 ERCP-cyto/biopsiesERCP-cyto/biopsies
 EUS with Fine Needle AspirationEUS with Fine Needle Aspiration
 Cholangioscopic directed biopsiesCholangioscopic directed biopsies
 Endoscopic TreatmentEndoscopic Treatment
 StentingStenting
 Endoscopic directed therapyEndoscopic directed therapy

40. Endoscopic Management
 Endoscopic-guided TherapyEndoscopic-guided Therapy
 Photodynamic TherapyPhotodynamic Therapy
Photodynamic Therapy w ith

41. ERCP-guided PDT
 Dumoulin et al.Dumoulin et al. GIE 2003GIE 2003
 PDT and Metal stent as palliation forPDT and Metal stent as palliation for
unresectable Klatskin’s tumorunresectable Klatskin’s tumor
24 patients vs. 20 controls24 patients vs. 20 controls
Median survival 9.9mos vs. 5.6mosMedian survival 9.9mos vs. 5.6mos
 Ortner et al.Ortner et al. Gastro 2003Gastro 2003
 Prospective randomized trial of PDT +stentingProspective randomized trial of PDT +stenting
vs. stenting alone in Klatskin’s tumorvs. stenting alone in Klatskin’s tumor
20 patients vs. 19 controls20 patients vs. 19 controls
Median Survival PDT group 493 vs.98 daysMedian Survival PDT group 493 vs.98 days

42. ERCP-guided PDT
 Zoepf et al. Am J of Gastro 2005Zoepf et al. Am J of Gastro 2005
 Randomized 32 pt’s to either PDT/stenting orRandomized 32 pt’s to either PDT/stenting or
stent alone for nonresectable CCAstent alone for nonresectable CCA
Photosan-3Photosan-3
9/16 received 2 PDT sessions, 1 pt 3 sessions9/16 received 2 PDT sessions, 1 pt 3 sessions
Median survival of PDT group wasMedian survival of PDT group was 21mos21mos
vs. 7mosvs. 7mos..
3/16 (PDT) developed cholangitis/infected3/16 (PDT) developed cholangitis/infected
biloma’sbiloma’s

43. ERCP-guided RFA
 Steel et al. GIE 2011Steel et al. GIE 2011
 22 patients (16 pancreatic and 6 CCA)22 patients (16 pancreatic and 6 CCA)
Deployment of RFA catheter successful inDeployment of RFA catheter successful in
21/2221/22
SEMS placed in all patientsSEMS placed in all patients
End point was safety at 30 and 90 daysEnd point was safety at 30 and 90 days
Endobiliary RFA treatment appears safeEndobiliary RFA treatment appears safe
Further studies are needed with longerFurther studies are needed with longer
durationduration

44. Summary
M e t a l v s P la s t ic
U n ila r e r a l v s B ila t e r a l s t e n t in g
D ia g n o s t ic
D ia g n o s t ic
C h o la n g io s c o p y w it h B io p s ie s
N o n - d ia g n o s t ic
E R C P v s . E U S f o r d ia g n o s is
M R C P
R e f e r r a l f o r E R C P
U n r e s e c t a b le
S u r g e r y
P o t e n t ia lly r e s e c t a b le
P R E S U M E D K L A T S K I N T U M O R

45. Conclusion
 Cholangiocarcinoma still a challenge to diagnoseCholangiocarcinoma still a challenge to diagnose
 Improved technology including EUS/FNA andImproved technology including EUS/FNA and
cholangioscopic directed biopsies have greatlycholangioscopic directed biopsies have greatly
improved yield in indeterminate stricturesimproved yield in indeterminate strictures
 Bilateral stenting may be preferred when possibleBilateral stenting may be preferred when possible
and is now made easier with the Zilver635and is now made easier with the Zilver635®® 6f6f
deployment system which allow simultaneousdeployment system which allow simultaneous
bilateral deploymentbilateral deployment
 Always use MRCP as a roadmap before ERCPAlways use MRCP as a roadmap before ERCP
 Never place uncovered metal stents without aNever place uncovered metal stents without a
prior diagnosisprior diagnosis