Download - Endoscopic management of bile duct cancers

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

Outline Pre-Procedure EvaluationPre-Procedure Evaluation

Imaging studies Imaging studies Determine ResectabilityDetermine Resectability

Tissue DiagnosisTissue Diagnosis ERCP-cyto/biopsies ERCP-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

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%

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

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

Local Unresectability

Involvement of bilateral hepatic duct up to Involvement of bilateral hepatic duct up to secondary radicles bilaterally, encasement/ secondary radicles bilaterally, encasement/ occlusion or PV/ HA occlusion or PV/ HA Determined by Imaging studiesDetermined by Imaging studies

CTscan, MRI/MRCP, ERCP and EUSCTscan, MRI/MRCP, ERCP and EUS Surgical ExplorationSurgical Exploration

Klatskin’s Tumor

LabsImaging

Resectable?

ERCP

Work-up

MRCP

Magnetic Resonance Cholangio-Pancreatography (MCRP)

Non-invasiveNon-invasive Detailed imaging of biliary systemDetailed imaging of biliary system

Roadmap for EndoscopistRoadmap for EndoscopistTargets therapyTargets therapyOptimizes TreatmentOptimizes TreatmentMinimizes complicationsMinimizes complications

• CholangitisCholangitis

ERCP

MRCP

MRCP

TARGETING THERAPYTARGETING THERAPY Hintze et al GIE 2001

Evaluated MRCP to aid in unilateral stent Evaluated 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 2003CT scan or MRCP to selectively target CT scan or MRCP to selectively target

drainage using metallic stentsdrainage using metallic stentsPalliation in 77% of patientsPalliation in 77% of patients

LabsImaging

Resectable?

ERCP

Traditional Work-up

MRCP

StentDX

Tissue Sampling by ERCP

Brush CytologyBrush Cytology Forceps BiopsyForceps Biopsy

Brush Cytology in Malignant Biliary StricturesAuthorsAuthors 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

ERCP-guided Biopsy of Malignant Biliary StricturesAuthorsAuthors 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%


Combined Brush and Biopsy of Malignant Biliary strictures

AuthorsAuthors YRYR BrushBrush BiopsyBiopsy Brush and Brush 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%


EUS-guided FNA

Useful in obtaining a diagnosis in pt’s with Useful in obtaining a diagnosis in pt’s with negative ERCP cytology and high index of negative 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 Tissue 9/10 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%

EUS-guided FNA

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) underwent 36pts (22 malignant) underwent cholangioscopy with biopsiescholangioscopy with biopsies

Accuracy was 89% for differentiating Accuracy was 89% for differentiating malignant vs. non-malignant stricturesmalignant vs. non-malignant strictures

Accuracy in pt’s with previous inconclusive Accuracy in pt’s with previous inconclusive ERCP brushings or biopsies was 82%ERCP brushings or biopsies was 82%

Cholangioscopy with biopsies

Draganov et al. GIE 2012Draganov et al. GIE 2012Compared conventional cytology Compared conventional cytology

brushings and biopsies and brushings and biopsies and cholangioscopic biopsies on 26 cholangioscopic biopsies on 26 patients (17 cancer)patients (17 cancer)

Cholangioscopic biopsies significantly Cholangioscopic biopsies significantly higher accuracy (84.6% vs. 58% vs. higher accuracy (84.6% vs. 58% vs. 38.5 %)38.5 %)

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 guided ERCP with cholangioscopic guided

biopsies-if negative??biopsies-if negative?? DDx- benign vs. malignantDDx- benign vs. malignant

Consider repeat ERCP with Consider repeat ERCP with cholangioscopic biopsies if mass is cholangioscopic biopsies if mass is seen and clinical suspicion highseen and clinical suspicion high

Endoscopic Palliation

StentingStenting Unilateral vs. Bilateral?Unilateral vs. Bilateral? Plastic vs. Metallic?Plastic vs. Metallic?

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 biliary Risk 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 1cm R 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%

Unilateral vs. Bilateral Stenting

Chang et al., GIE 1998Chang et al., GIE 1998 Evaluated the outcomes of 98 patients with Evaluated the outcomes of 98 patients with

unresectable CCA who underwent unilateral or unresectable CCA who underwent unilateral or bilateral stentingbilateral stenting

Retrospective reviewRetrospective reviewPatients with bilateral drainage had a Patients with bilateral drainage had a

significant survival advantage 225 vs. 80 significant survival advantage 225 vs. 80 daysdays

Cholangitis 11% (32% in pts with un-Cholangitis 11% (32% in pts with un-drained segments)drained segments)


De Palma et al. GIE 2001De Palma et al. GIE 2001 Compared unilateral vs. bilateral hepatic duct Compared unilateral vs. bilateral hepatic duct

drainagedrainage 157 patients randomly assigned prospectively157 patients randomly assigned prospectively Unilateral group had higher stent insertion Unilateral group had higher stent insertion

success and less complicationssuccess and less complications Successful drainage, survival comparable in Successful drainage, survival comparable in

both groupsboth groups ConclusionConclusion:bilateral stenting not justified and may :bilateral stenting not justified and may

increase complicationsincrease complications


De Palma et al. GIE 2003De Palma et al. GIE 2003 Evaluated Unilateral metal stent placement for Evaluated 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 59/61Successful biliary drainage in 59/61Successful biliary drainage in 59/61Cholangitis 5%Cholangitis 5%Median stent patency of 169 daysMedian stent patency of 169 days


Naitoh et al. J Gastroenterol Hep 2009Naitoh et al. J Gastroenterol Hep 2009 Retrospective series of 46 patients Retrospective series of 46 patients

showed better outcomes with bilateral vs. showed better outcomes with bilateral vs. unilateral stentingunilateral stentingImproved stent patency bilateral group Improved stent patency bilateral group

488 vs. 210 days for unilateral group 488 vs. 210 days for unilateral group (p=.009)(p=.009)

Endoscopic Palliation

PLASTIC vs. METAL?PLASTIC vs. METAL?

Plastic Stents Metal Stents

Median Patency 3-Median Patency 3-5mos5mos

Average diameter is Average diameter is 10Fr (3.3mm)10Fr (3.3mm)

Stent change q3mos.Stent change q3mos.

Median Patency 6-Median Patency 6-8mos8mos

Self expandable up to Self expandable up to 30Fr (10mm)30Fr (10mm)

PermanentPermanent

Plastic vs. Metal?

Life ExpectancyLife Expectancy Quality of LifeQuality of Life CostCost Physician ExpertisePhysician Expertise

No Difference in Survival

ERCP Complications

ImmediateImmediate CholangitisCholangitis

Antibiotics pre/post procedureAntibiotics pre/post procedureSelective Opacification during ERCPSelective Opacification during ERCP

PancreatitisPancreatitis BleedingBleeding

LateLate Stent OcclusionStent Occlusion

New technology

Cook Zilver635Cook Zilver635®® system system UUncovered metal stent deployment system that uses a ncovered 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 introducer Less need to dilate Hilar strictures as the introducer system is much smallersystem is much smaller

Allows simultaneous deployment of bilateral stents Allows simultaneous deployment of bilateral stents through the scopethrough the scope

• This allows easier access in the future to each This allows easier access in the future to each side of the biliary system as they are side by side side of the biliary system as they are side by side and not in the Y configurationand not in the Y configuration

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 10 Side by Side deployment achieved in all 10

cases attemptedcases attempted Additional transpapillary stenting was Additional transpapillary stenting was

performed for future accessperformed for future access Conclusion- works great but would like longer Conclusion- works great but would like longer

lengths that may bridge papillalengths that may bridge papilla

Simultaneous deployment video

Tips and tricks for deployment

Spray Pam for lubrication Spray Pam for lubrication Consider a small sphincterotomyConsider a small sphincterotomy Although different sizes exist, try and place Although 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 2 ndnd stents within stents within stents to allow for future access for re-stents to allow for future access for re-intervention intervention

Outline Pre-Procedure EvaluationPre-Procedure Evaluation

Imaging studies Imaging studies Determine ResectabilityDetermine Resectability

Tissue DiagnosisTissue Diagnosis ERCP-cyto/biopsies ERCP-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

Endoscopic Management

Endoscopic-guided TherapyEndoscopic-guided Therapy Photodynamic TherapyPhotodynamic Therapy

Phot odynamic Therapy w it h

ERCP-guided PDT

Dumoulin et al.Dumoulin et al. GIE 2003 GIE 2003 PDT and Metal stent as palliation for PDT and Metal stent as palliation for

unresectable Klatskin’s tumorunresectable Klatskin’s tumor24 patients vs. 20 controls24 patients vs. 20 controlsMedian survival 9.9mos vs. 5.6mos Median survival 9.9mos vs. 5.6mos

Ortner et al.Ortner et al. Gastro 2003 Gastro 2003 Prospective randomized trial of PDT +stenting Prospective randomized trial of PDT +stenting

vs. stenting alone in Klatskin’s tumorvs. stenting alone in Klatskin’s tumor20 patients vs. 19 controls20 patients vs. 19 controlsMedian Survival PDT group 493 vs.98 daysMedian Survival PDT group 493 vs.98 days

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 or Randomized 32 pt’s to either PDT/stenting or

stent alone for nonresectable CCAstent alone for nonresectable CCAPhotosan-3 Photosan-3 9/16 received 2 PDT sessions, 1 pt 3 sessions9/16 received 2 PDT sessions, 1 pt 3 sessionsMedian survival of PDT group was Median survival of PDT group was 21mos 21mos

vs. 7mosvs. 7mos..3/16 (PDT) developed cholangitis/infected 3/16 (PDT) developed cholangitis/infected

biloma’sbiloma’s

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 in Deployment of RFA catheter successful in 21/22 21/22

SEMS placed in all patientsSEMS placed in all patientsEnd point was safety at 30 and 90 daysEnd point was safety at 30 and 90 daysEndobiliary RFA treatment appears safe Endobiliary RFA treatment appears safe Further studies are needed with longer Further studies are needed with longer

durationduration

Summary

M e t a l v s P l a s t i c

U n i l a r e r a l v s B i l a t e r a l s t e n t i n g

D i a g n o s t i c

D i a g n o s t i c

C h o l a n g i o s c o p y w i t h B i o p s i e s

N o n - d i a g n o s t i c

E R C P v s . E U S f o r d i a g n o s i s

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 l e

S u r g e r y

P o t e n t i a l l y r e s e c t a b l e

P R E S U M E D K L A T S K I N T U M O R

Conclusion

Cholangiocarcinoma still a challenge to diagnoseCholangiocarcinoma still a challenge to diagnose Improved technology including EUS/FNA and Improved technology including EUS/FNA and

cholangioscopic directed biopsies have greatly cholangioscopic directed biopsies have greatly improved yield in indeterminate stricturesimproved yield in indeterminate strictures

Bilateral stenting may be preferred when possible Bilateral stenting may be preferred when possible and is now made easier with the Zilver635and is now made easier with the Zilver635®® 6f 6f deployment system which allow simultaneous deployment system which allow simultaneous bilateral deployment bilateral deployment

Always use MRCP as a roadmap before ERCPAlways use MRCP as a roadmap before ERCP Never place uncovered metal stents without a Never place uncovered metal stents without a

prior diagnosisprior diagnosis