Robert H. Hawes, M.D.Center for Interventional Endoscopy at AdventHealth Orlando

Medical Director,Institute for Minimally Invasive Therapy

Professor of Internal Medicine,University of Central Florida College of Medicine

University of California, Irvine12th Annual Gastroenterology & Hepatology Symposium

Disney’s Californian Hotel & SpaAnaheim, CA

February 28-29, 2020

Biliary endoscopy: Emerging technologies

Disclosures

• Olympus• Consultant

History of ERCP

• Diagnostic test (1968 – 2002)

• Therapeutic

• Sphincterotomy: 1974 (Kawai & Classen)

• Cholangioscopy: 1978 (Nakajima)

• Stent: 1979 (Soehendra)

• Plastic metal

Kawai – GIE 1974;20(4):148-51Classen – Dtsch Med Wochenschr 1974;99(11):496-7Nakajima – Gastrointest Endosc 1978;24(4):141-45Soehendra – Dtsch Med Wochenschr 1979;104(6):206-7

ERCP is 52 years old. The last major innovation was 41 years ago

ERCP for biliary disease

• Stones

• Cancer

• Benign strictures

• Inflammatory - PSC

• Post operative

ERCP for bile duct stones

• Sphincterotomy/balloon dilation Balloon/basket: 80% success

• Difficult bile duct stones

• Mechanical lithotripsy

• Large balloon dilation 90% success (index ERCP)

• SOC + EHL/Laser

ERCP for malignant biliary obstruction• Diagnosis

• Brush

• Bile 60-70%

• Blind biopsy

• SOC + targeted biopsy – 90%

• Therapy• Palliative

• Stent: plastic metal

• Therapy• Photodynamic therapy

• RFA

ERCP for benign biliary strictures

• PSC : balloon dilation

• Post-operative : Multiple plastic metal

How can we improve biliary endoscopy?

• Improve management of bile duct stones?

• Improve diagnosis of indeterminate biliary strictures?

• Improve stenting for malignancy?

• Improve treatment of benign biliary strictures

• Alternatives to ERCP?

How can we improve management of bile duct stones?

• Improve success rate for index ERCP

• Cannulation

• stone extraction

• Improve safety

• Pancreatitis

• Cholangitis

• Perforation

• Reduce time

• Reduce cost

• Reduce technical complexity

Accomplishing these goals is dependenton training and developing algorithms,

not on new technology

How can we improve diagnosis of indeterminate biliary strictures?

• Improve blind sampling

• Improve tissue acquisition in targeted biopsies

• EUS guided tissue acquisition

Flourescence in situ hybridization (FISH) for the diagnosis of cholangiocarcinoma (CCA) in PSC: a systematic review and meta-

analysis

• Pooled data for CCA in PSC• 8 studies/828 patients

• Sens: 68% (95% CI, 61%-74%

• Spec: 70% (95% CI, 66%- 73%

• Pooled data for FISH polysomy• 6 studies/690 patients

• Sens: 51% (95% CI, 43% - 59%)

• Spec: 93% (95% CI, 91%-95%)

Navaneethan U et al. Gastrointest Endosc 2014;79(6):943-950

Detection of polysomy does not meanPatients will develop cancer

How good is EUS FNA currently?

22G 22G 25G 25Gp-

valueNo Suction Suction No Suction Suction

(n=88) (n=88) (n=88) (n=88)

Diagnostic cell block 71 (80.7) 63 (71.6) 56 (65.9) 67 (73.6) 0.177

ROSE – Diagnostic accuracy: % (95% CI) 99 (94-100) 93 (86-98)) 99 (94-100) 99 (94-100) 0.06

Bang et al. UEGW, 2016

• 352 patients

• Suction vs no suction

• 22 vs 25 gauge needle

• Standard bevel

Overall diagnostic accuracy: 96.6%

Bang et al. Clin Gastroenterol Hepatol 2018;16(11):1820-1828

ProCoreCook Shark-Core

Medtronic

EasyShot IIIOlympus

AcquireBSC

New generation FNB needles

Franseen FNB vs. Standard FNA

FNB FNA p-value(n=46) (n=46)

ROSE - Diagnostic adequacy: n (%) 46 (100) 44 (95.7) 0.495

ROSE - Total no. of passes for diagnostic adequacy: Median (IQR) 1 (1-1) 1 (1-1) 0.929

Specimen bloodiness: n (%) Mild 12 (26.1) 16 (34.8) 0.736Moderate 29 (63.0) 26 (56.5)

Severe 5 (10.9) 4 (8.7)

Cell block - Diagnostic adequacy: n (%) 45 (97.8) 38 (82.6) 0.030

Cell block - Diagnostic accuracy: n (%) 43 (93.5) 37 (80.4) 0.063

• Randomized trial• n=46 with solid pancreatic mass lesions• FNA and FNB performed in all patients

Bang et al. Gut 2018;67(12):2081-2084

Franseen FNB vs. Standard FNA

FNB FNA p-value

Median total tissue area, IQR (mm2): 6.1 (2.2-9.9) 0.28 (0.05-0.93) < 0.0001

Median total tumor area, IQR (mm2): 0.68 (0.23-2.8) 0.099 (0.004-0.3) < 0.0001

Desmoplastic fibrosis present: n (%) 33 (84.6) 13 (33.3) < 0.0001

Median area of desmoplastic fibrosis, IQR (mm2): 3.9 (0.5-8.2) 0 (0-0.11) < 0.0001

Architecture retained: n (%) 43 (93.5) 9 (19.6) < 0.0001

Suitable for immunohistochemistry studies: n (%) 41 (100) 28 (68.3) < 0.0001

Bang et al. Gut 2018;67(12):2081-2084

How can we improve stenting for malignancy?

• Drug eluding stents?

• Delivery of PDT with stents?

• RFA?

• EUS guided biliary drainage?

Efficacy of a metal stent with chemo eluding membrane (MSCPM) vs covered metal stent (CMS) for malignant biliary

obstruction

• Prospective comparative study

• Paclitaxel-incorporated membrane

• 106 patients: MSCPM – 60, CMS - 46

Endpoint P valueStent patency NS

Survival NS

AE NS

Jang SI et al. Dig Dis Sci 2013;58(3):865-71

Combining photo-sensitizer with metal stent for PDT treatment

• Polymeric photo-sensitizer (pullulan acetate-conjugated pheophorbide) incorporated into a metal stent

• In bench top model – PDT-stent sustained photodynamic activities for at least 2 mo

• After light exposure, the PDT-stent successfully generated cytotoxic singlet oxygen in the surrounding tissues

• Demonstrated apoptotic degradation of tumor cells in tumor mouse models

• Endoscopic biliary in-stent PDT treatments in mini pigs suggested efficacy of PDT-stent in cholangiocarcinoma

• Has potential for combined therapy in cholangiocarcinomaBae BC et al. Biomaterials 2014;35(30):8487-95

Can RFA improve management of malignant biliary obstruction?

• Prospective database, retrospective review

• 64 patients with malignant biliary obstruction

• Metal stent + RFA vs Metal stent alone

• Patients matched for age, diagnosis, performance status, palliative chemo

• Technical success 100% in both groups

• Multivariable Cox proportional regression analysis showed RFA to be an

independe3nt predictor of survival [HR 0.29 (0.11-0.76), p = 0.012

Sharaiha RZ et al. Dig Dis Sci 2014;59(12):3099-102

How can we improve biliary endoscopy?

• Improve management of bile duct stones?

• Improve diagnosis of indeterminate biliary strictures?

• Improve stenting for malignancy?

• Improve treatment of benign biliary strictures

• Alternatives to ERCP?

RT of EUS-guided biliary drainage vs. PTC in failed ERCP

Lee TH et al. Clin Gastroenterol Hepatol 2016;14(7):1011-19

Variable EGBD(n=34)

PTBD(n=32) P value

Technical success,% 94.1 96.9 0.008(NI margin 15%)

Functional success, % 87.5 87.1 0.4

Adverse events, % 8.8 31.2 0.02

Re-interventions, % 8 17 0.01

Median Length of Stay 6 (3-14) 12 (4-24) 0.001

RT comparing EUS and ERCP for primary biliary decompression in pancreatic cancer

ERCP EUS Risk ratioP

(n=34) (n=33) (95% CI)

Adverse events 5 (14.7) 7 (21.2)0.69 (0.24 -

1.97)0.487

Moderate severity: n (%) 2 (5.9%) 2 (6%) 0.97 (0.15-6.49) 0.999-

Technical success: n (%) 32 (94.1) 30 (90.9)1.04 (0.90 -

1.19)0.673

Stent dysfunction requiring reintervention: n (%)

1 (2.9) 1 (3.0)0.97 (0.06 -

14.9)0.999

Total bilirubin < 50% baseline at 2 week post-procedure: n (%)

31 (91.2) 32 (97.0)0.94 (0.83 -

1.06)0.614

Surgical resection : n (%) 5 (14.7) 5 (15.2)0.97 (0.31 –

3.04)0.999

JY Bang et al. Gastrointest Endosc 2018;88(1):9-17

Take home points• ERCP and now EUS form the basis for biliary endoscopy

• The indications for biliary endoscopy have not changed over the

last 50 years

• EUS (tissue acquisition/interventions), metal stents and single

operator cholangioscopy represent the most impactful

technologies influencing the practice of biliary endoscopy

• Optimal utilization of existing technologies rather than looking for

major new technologies should occupy the time of a young biliary

endoscopist

AdventHealth Orlando

ShyamVaradarajulu

MuhammadHasan

UdhayNavaneethan

Ji YoungBang