Prospective Evaluation of Single-Operator Peroral Cholangioscopy in Liver Transplant Recipients Requiring an

Evaluation of the Biliary Tract

Domingo Balderramo et alLiver Transplantation: Volume 19, Issue 2, pages 199–

206, February 2013Presented by:Dr. Amitesh Kumar Moderator:Dr. Neeraj Saraf

Introduction• Biliary complications occur in upto 20% patients after deceased donor LT • ERCP

first-line therapeutic approach - confirms diagnosis - allows therapy - success rate - 80% to 100% [1, 4, 6] limitations - cannot directly visualize the bile duct

- cannot specify characteristics of stricture or filling defect• Single-operator cholangioscopy (SOC) system using the SpyGlass direct

visualization system (Boston Scientific Corp., Natick, MA) Main indication:

o evaluation of indeterminate pancreatico- biliary strictureso treatment of large, difficult to remove common bile duct stones

high procedure success rate high accuracy in distinguishing benign and malignant lesions [12-17]

Aim of the study

To describe both cholangioscopic and histological findings of biliary lesions in liver transplant recipients using the SOC-SpyGlass direct visualization system

Study Design

• Prospective

• Descriptive

• Single center - Hospital Clinic in Barcelona, a tertiary care hospital

Study Population• Inclusion criteria: Adult recipients of deceased donor liver transplant with biliary

complications referred for ERCP between June 2009 and July 2011

• Exclusion criteria: refusal to participate in the study inability to provide informed consent pregnancy living donor liver transplant previous Roux-en-Y hepaticojejunostomy confirmed malignancy of the biliary tree advanced liver failure coagulopathy hemodynamic instability sepsis

Procedures• ERCP and cholangioscopy - all patients

• Biliary sphincterotomy - if not done previously

• If anastomotic stricture present

following were evaluated-Borders -Ulcers -concentricity versus eccentricity

2 patterns a) scarring and minimal inflammatory changesb) edema, ulceration and severe inflammatory changes

2 - 4 biopsies taken stents placed as required

• If anastomotic stricture absent

descriptive findings of anastomosis and bile duct recorded 2 to 4 biopsies of anastomosis taken endoscopic therapy of any biliary complication (eg: stone removal)

Outcomes and Definitions• Main outcome measure:

-feasibility of procedure -adequate visualization -ability to obtain biopsy

• Secondary outcomes -impact on endoscopic therapy-incidence of adverse events-total cholangioscopy time

• Plastic stents removed every 3 months stricture evaluated If A.S. still present further therapy with balloon dilation and stent placement

• Stricture considered to be relieved- if no evidence of stenosis on cholangiography and free passage of extraction balloon

• ERCP therapy defined as failing - when there was indication for percutaneous transhepatic cholangiography or surgery during follow-up

RESULTS• 23 patients met the inclusion criteria

• 7 patients were excluded hemodynamic instability (n = 2) bacterial infection (n = 2), cytomegalovirus infection (n = 1) recent T-tube extraction (n = 1) previous postsphincterotomy bleeding (n = 1)

• Finally, 16 patients were included anastomotic stricture -12 CBD stones - 2 bile leak - 1 SOD – 1

• Complete SOC successful in 15 of 16 (93.8%) In 1 patient, cholangioscope could not be advanced across the stricture

• 5patients - T-tube placed previously

• Total cholangioscopy time was 26.8 ± 10.1 minutes.

Summary of demographic and clinical characteristics and cholangioscopic findings

SL NO

SEX/ AGE

ETIOLOGY

COMPLICATION

A.S. TYPE

BORDER A.S. PATTERN ADDITIONAL FINDINGS

NEED FOR SURGERY

TIME FROM LT to ERCP (MNTH)

STENTING PERIOD (DAYS)

ERCP WITH STENTING

1 M/54 HCV AS CONC IRR A STONES NO 13.8 238 4

2 M/65 HCV AS CONC IRR A NO NO 28.3 309 5

3 M/47 ALD AS CONC REG A NO NO 5.8 113 2

4 M/48 HCV AS ECC IRR A STONES NO 12.2 131 2

5 M/64 HCV AS CONC IRR A NO NO 4.2 175 3

6 M/65 HCV AS CONC IRR A NO YES 12.6 * *

7 F/49 HCV AS CONC IRR A NO NO 27.1 124 2

8 M/60 HCV, HBV

AS CONC IRR A NO NO 64.5 195 3

9 M/45 HCV AS ECC IRR A NO NO 2.1 178 2

10 F/66 HCV AS CONC IRR B STONES YES 30.4 720 8

11 M/43 HCV AS ECC IRR B STONES NO 36.2 443 5

12 M/51 HCV AS ECC IRR B NO YES 7.6 207 3

13 F/73 HCV STONE REG CONT NO 153.8 - -

14 F/41` ALF STONE REG CONT NO 230.1 - -

15 F/45 ALF BILE LEAK

REG CONT NO 1.9 101 1

16 M/48 HCV SOD REG CONT STONES 13.8 - -

Cholangioscopy Findings• Two patterns in A.S.

(A) mild erythema and scarring (n = 9)(B) severe edema, erythema, ulceration

with sloughing (n = 3)

• Patients without A.S. - pale mucosa, mild edema, no stenosis (C)

• Biliary epithelium of native or graft bile duct outside the anastomosis - no significant abnormalities

• Additional CBD stones noted which were not seen in initial cholangiograms for 5 patients (31%) (D)

Clinical evolution according to cholangioscopic findings in patients with A.S.

Characteristic Pattern A (n=9) Pattern B (n=3) P Value

Duration of stenting (days) 167±87 457±257 0.01

ERCP procedures with stenting 2.7±1.2 5.3±2.5 0.03

Success of endoscopic therapy [n(%)] 8(88.9) 1(33.4) 0.13

Characteristics of patients with A.S.

Variable Pattern A (n=9) Pattern B(n=3) P value

Baseline data

Age (years 55.6±8.4 53.9±11.4 0.81

Male sex [n(%)] 8(88.9) 2(66.7) 0.45

HCV etiology [n(%)] 8(88.9) 3(100) >0.99

Post liver transplant data

Bile leak[n(%)] 2(22.2) 0(0) >0.99T – tube use[n(%)] 3(33.3) 0(0) 0.51

Acute cellular rejection[n(%)] 1(11.1) 0(0) >0.99

CMV infection[n(%)] 2(22.2) 0(0) >0.99

Hepatic artery thrombosis[n(%)] 1(11.1) 0(0) >0.99

Immunosuppression at ERCP[n(%)]

Tacrolimus 3(33.3) 2(66.7) 0.53

Cyclosporine 3(33.3) 0(0) 0.51

Mammalian target of rapamycin inhibitor 2(22.2) 1(33.3) >0.99

Prednisolone 4(44.4) 0(0) 0.49

Mycophenolate mofetil 2(22.2) 0(0) >0.99

ERCP data

Time from LT to ERCP (months) 14.9(9.5) 24.7(15.1) 0.24

Time from LT to ERCP >12 MONTHS [n(%)] 6(66.7) 2(66.7) >0.99

• All patients with A.S. - followed up until the A.S. was resolved or surgery or percutaneous transhepatic cholangiography was needed

• Stenting period: pattern B (457 days) > pattern A (167 days) [P = 0.01] • Maximum number of stents placed in any patient = 4• Response to endoscopic therapy: pattern A(88.9%) > pattern

B(33.4%) [P = 0.13]• Complications: 1 patient (6.2%) - cholangitis • 3 patients with A.S. underwent hepaticojejunostomy because:

I. inability to traverse the stricture with a guide wire II. development of a liver abscess (unrelated to procedure)III. lack of a response despite multiple sessions

• No restenosis during follow-up• No significant differences in age, sex, post liver transplant evolution,

or time from transplant to ERCP between pattern A and pattern B

Histopathological Findings

• Adequate tissue – 81% patients

• Pattern A:(1) Nuclear pseudostratification,

prominent nucleoli, focal mucinous metaplasia, and focal intraepithelial inflammatory cells (mostly neutrophils)

(2) Subepithelial mucinous biliary glands associated with a chronic inflammatory infiltrate

• Pattern B:(1) Moderate fibrinous material with

scattered neutrophilic aggregates(2) Mild nuclear pseudostratification

and abundant intraepithelial neutrophils

• Patients without A.S. - normal columnar epithelial biliary cells with basal nuclei

• There were no findings compatible with graft rejection, fungal infection, cytomegalovirus infection, or post transplant lymphoproliferative disorder

Discussion• Outcomes of patients who develop A.S. or other

complications after liver transplant has improved with advances in surgical, endoscopic and radiological management [2-5, 29]

• The main findings of this study indicate that (1) ERCP-guided SOC with the SpyGlass system is feasible and

can successfully be performed in LT recipients with biliary complications

(2) 2 different cholangioscopic AS patterns can be easily identified and may help to predict responses to therapy

(3) histological findings in ASs show nonspecific inflammatory changes

• Responses to endoscopic treatment in LT recipients with A.S. may differ according to the cholangioscopy pattern

• Patients with pattern A: responded better than patients required fewer days of stenting to achieve a final response to

endoscopic therapy

• Patients with Pattern B needed more ERCP sessions with stenting require prolonged therapy should be considered for early surgery if there is no good

response after 1 or 2 sessions to prevent a prolonged course of ERCP and it’s complications

Suggested treatment algorithm based on findings of SOC

Limitations of the study• Small sample size

• Single-center study

• Presence of a learning curve with this procedure

• Patients who underwent living donor LT or recipients of transplants from donors after cardiac death, who have a higher incidence of A.S. versus recipients of cadaveric donors were not included

Conclusion

• ERCP-guided SOC with the SpyGlass system is feasible and can be successfully performed in liver tranplant recipients with biliary complications

• Cholangioscopic findings of A.S. may predict the response to ERCP therapy

Suggested future studies

• Further prospective studies comparing ERCP alone to ERCP plus SOC

• Large prospective, multicenter study that could evaluate predetermined criteria based on patient characteristics, surgical characteristics of transplants, radiographic and cholangiographic criteria, and visual characteristics under SOC as well as correlations of specific endpoints with the outcomes of endoscopic therapy, the need for surgical reinterventions, and clinical outcomes

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Thankyou