Cholangiocarcinoma (Gastroenterologists Perspectives) by AP Dr.Tin Moe Wai.pdf

Cholangiocarcinoma as gastroenterologist perspective

1. Cholangiocarcinoma:
Gastroenterologist Perspective
AP Dr. Tin Moe Wai
Senior Consultant Gastroenterologist
Yangon General Hospital
Hepatobiliary Symposium 2
nd
March, 2024

2. Perspectives
•in Diagnostic endoscopy
•in Preoperative endoscopy for resectable CCA
•in Therapeutic endoscopy for unrectable CCA

3. Background
•Incidence of CCA is increasing both in the US and globally
•Remains predominantly a threat in its early detection and
diagnosis
•Advances in endoscopic, radiographic, and genomic analysis
methods
–provided predictors of success before undergoing definitive therapies
–allow a change in management from only palliative surgery to a
curative therapy by resection or liver transplantation
•The growth of therapeutic endoscopy with available
technologies and evolving techniques become a fundamental
cornerstone of CCA:
–biliary drainage to improve quality of life and proceed with oncologic
therapies.

4. Role of endoscopy
•Most patients will need some form of endoscopic
intervention
–for tissue diagnosis or
–to gain biliary drainage
•The only patients where this will not be required
–those with local disease having up front surgery
–those with advanced disease and or underlying frailty
(should be for best supportive care from the outset
where the prognosis is poor, with a median survival time
of just 10 weeks)
Koch C, Franzke C, Bechstein WO, et al. 2020;101(4):458-465

5. Diagnostic advances in endoscopy
•Diagnosis aimed to accurately differentiate
between benign biliary strictures from early
cholangiocarcinoma
•Diagnostic modalities include
–ERCP
–Cholangioscopy
–Confocal Laser Endomicroscopy
–EUS FNA
–IDUS

6. ERCP
•Japanese guidelines recommend endoscopic retrograde
cholangiopancreatography (ERCP) as the next imaging test after CT
•Many centers have globally replaced ERCP as a means of the initial
diagnostic modality for biliary pathology with the advent of
noninvasive diagnostic modalities, such as MRI and MRCP
•The sensitivities of MRCP vs. ERCP in differentiating between benign
strictures and CCA were noted at 74% and 70%, respectively (Park
MS et al. Radiology. 2004)
•ERCP remains invaluable as it continues to be the modality of
choice for tissue acquisition
H. Kawashima et al. Digestive Endoscopy 2022; 34: 1147–1156

7. ERCP Tissue Acquisition
•Tissue samples via ERCP are obtainable by
–bile duct aspirate
–brush cytology, and
–endobiliary biopsies
Study Method Year Sensitivity Specificity
Fritcher EGB Brush Cytology 200942%
Levy MJ Brush Cytology+FISH 200893% 100%
Dudley JC Brush Cytology+NGS 201685%
Nanda A Brush Cytology+FISH+
Biopsy
201582% 100%
A. A. Nakshabandi And J. H. Lee Expert Review Of Gastroenterology & Hepatology 2023, VOL. 17, NO. 2,
175–187

8. ERCP Limitations without tissue diagnosis
Inflammatory
Malignant
Postoperative

9. Cholangioscopy
Method Study by YearSensitivity % Specificity %
Visualization alone Urban 201990-100 76-96
Miniature forceps Navaneethan U201586 100
Biopsy+ rapid onsite
examination of touch
imprint cytology
Navaneethan U201694
Brush cytology +
intraductal biopsy
Navaneethan U201659.4 100
direct single-operator
peroral cholangioscopy
system
[DSOC]
SpyGlass
A. A. Nakshabandi And J. H. Lee Expert Review Of Gastroenterology & Hepatology 2023, VOL. 17, NO. 2,
175–187

10. Spyglass Cholangioscopy
•Our case on 1
st
March 2024

11. NBI Cholangioscopy
Used when MRCP and ERCP failed to identify definite mucosa mass
use of NBI cholangioscopy demonstrated infiltrative tumor in 4 of 13 cases
presenting as irregular mucosal surface and altered color of the tumor
vasculature, especially at the marginal sites
Jang JW et al. Ann Surg Treat Res. 2017 Sep;93(3):125–129

12. Confocal Laser Endomicroscopy

13. ERCP guided CLE Vs Sampling
ERCP guided CLE ERCP guided sampling
Sensitivity 98% 45%
Specificity 67% 100%
PPV 71% 100%
NPV 97% 69%
Meining A, Chen YK, Pleskow D, et al. Gastrointest Endosc. 2011
Nov 1;74(5):961–968

14. EUS (Endoscopic Ultrasound)
•visualization of the tumor, the hilum, the celiac
axis, and the surrounding lymph nodes, thus,
allowing for staging
•EUS FNA
–100% positive predictive value and minimal post-
procedure complications compared to ERCP
Sensitivity Specificity
EUS alone 43% 79%
EUS FNA 89% 100%
Urban O et al. Gastroenterol Res Pract. 2019

15. EUS FNA
•to obtain Histological Diagnosis
•iCCA
–the composition of iCCA cells resembles those of
hepatocellular carcinoma
•eCCA
–difficult to target,
–difficult to puncture
–Contraindicated in liver transplant candidate for risk of
tumor seeding
–Peritoneal metastasis occurred in 83% of the patients who
underwent this procedure, compared to 8% of those who
did not
Heimbach JK, Sanchez W, Rosen CB, et al. HPB. 2011 May;13(5):356–360

16. IDUS (Intraductal Ultrasound)
•Diagnosis
–Sensitivity – 93%
–Specificity - 89.5%
–Accuracy - 91%
•assist in local staging
•as sensitive as ERCP with transpapillary biopsy
[89% vs. 83%] but more specific [92% vs. 42%]
Urban O et al. Gastroenterol Res Pract. 2019

17. Diagnostic capabilities of each imaging modality

18. Preoperative endoscopy
•For resectable CCA
–Mapping biopsy
–Preoperative drainage

19. Mapping Biopsy
•used to diagnose superficial carcinoma in situ (CIS) extensions that cannot be diagnosed
imaging to confirm the optimal surgical planning
•5-year survival rate was significantly better in R0 (negative margins) cases than in R1cis
(positive margins for CIS) cases
Preoperative diagnosis and drainage of perihilar cholangiocarcinoma. The planned hepatectomy for this patient was right + caudate lobe
hepatectomy. (a) Endoscopic cholangiopancreatography findings show no evidence of extension at the segment IV bile duct (B4) confluence
(arrow). (b) Intraductal ultrasonography (IDUS) findings at the B4 confluence: no evidence of extension. (c) IDUS findings at the site of stenosis. (d)
Biopsy of the B4 confluence site (pathological diagnosis: benign). (e) Biopsy of the stenotic site (pathological diagnosis: adenocarcinoma). (f) Biopsy
of the downstream site (pathological diagnosis: benign). (g) A plastic stent (7F, 9 cm) is placed across the papilla (inside stent) for preoperative
drainage
H. Kawashima et al. Digestive Endoscopy 2022; 34: 1147–1156

20. Preoperative Drainage
•strongly recommended for patients scheduled to undergo
major hepatectomy
•recommended the most appropriate
preoperative drainage procedure
•drainage method of choice nowaday
–inside stent (IS) i.e above the papilla because of patient
discomfort and necessity of bile replacement with ENBD
Nagigo et.al. J Hepatobiliary Pancreat Sci. 2021;28:26–54
unilateral drainage in the future
remnant liver lobe using ENBD

21. Therapeutic Endoscopy in
unresectable CCA
•ERCP & Stenting
–Unilateral or Bilateral
–Plastic stent or Metallic stent
•ERCP guided ablative therapy
–Photodynamic therapy
–Radiofrequency ablation
•EUS guided biliary drainage
–Choledochoduodenostomy
–Hepaticogastrostomy
–Antegrade approach

22. ERCP Drainage of Unresectabe CCA
•Plastic or metal stent(stent in stent, side by side)
•Unilateral or Bilateral
•Depend on location of stricture related to anatomy of biliary
tree

23. ERCP Drainage of Unresectabe CCA
•Bilateral drainage was reported to result in longer TRBO (time to recurrent
biliary obstruction)
•Both Japanese and ASGE2 guidelines recommend drainage for
unresectable PHCC using plastic stents (PS) or uncovered self-expandable
metallic stents (SEMS)
•uncovered SEMS produce a longer TRBO than PS
•drainage of >50% of the liver volume is
superior to drainage of a lower volume
•drainage of >35% of the liver volume is
sufficient
•drainage of >50% is required in cases of
liver dysfunction

24. Plastic Vs. Metal stent
Metal stent placement
•the most effective treatment of
inoperable malignant common
bile duct stricture.
•cost effective in patients without
hepatic metastasis
•plastic stent should be placed in
patients with spread of the
tumor to the liver
•tissue ingrowth through metal
stents causing intrahepatic
biliary obstruction
•many therapeutic endoscopists
favoring PS in managing
intrahepatic strictures
Metal stent place
A. A. Nakshabandi And J. H. Lee Expert Review Of Gastroenterology & Hepatology 2023, VOL.
17, NO. 2, 175–187

25. Distal 6 3 0 8 2
Proximal 26 18 6 20 33
2019 2020 2021 2022 2023
6
3
0
8
2
26
18
6
20
33
0
5
10
15
20
25
30
35
No
of patients
Cholangiocarcinoma (YGH, GI data )
Total
ERCP
616 332 118 422 782

26. ERCP directed ablative therapies
•primary palliative therapies for CCA or
•adjunct therapies for SEMS
•combining endobiliary ablation techniques
and stenting
–prolongs stent patency and
–patient survival without significant adverse events

27. ERCP directed Photodynamic Therapy
Vítor Ottoboni et al.ABCD Arq Bras Cir Dig 2020;33(1):

28. ERCP directed Photodynamic Therapy
Aaron J Quyn et al HPB 2009Ortner et al gastroenterology 2003
PDT improves survival in Cholangio Carcinoma
n=20
n=19
Median Survival
98 vs 493 days
Surgery
PDT + StentCT + Stent

29. ERCP directed RFA
Gastrointest Endosc 2011
Pre RFA Post RFA

30. ERCP directed RFA
Kaplan-Meier survival curve comparing RFA with
stenting versus biliary stenting alone
Rebhun J et al. World J Gastrointest Endosc March 16, 2023 Volume 15 Issue 3
Forest plot of mean stent survival among treatment groups
along with difference in survival

31. EUS guided biliary drainage

32. EUS guided biliary drainage
•Have revealed multiple successful novel approaches
to otherwise complex pathologies requiring surgery
or, in some instances, no possible interventions
•The widespread use is tethered by the lack of
standardization of both a training curriculum and the
procedure itself and dedicated accessories and
devices

33. Conclusion
•Advances in diagnostic endoscopic guided modalities aimed to accurately
differentiate between benign biliary strictures from early
cholangiocarcinoma.
•Endoscopic sampling techniques and devices have improved cytology
sampling
•Recent advances in the use of cytopathology with next-generation
sequencing can provide higher diagnostic sensitivities, prognostic, and
even predictive information for therapeutic purposes.
•Most cases of CCA are unresectable.
•Several new novel approaches are described to maintain biliary drainage,
including EUS BD, all of which are technically feasible but require further
validation and dedicated devices

34. Multidisplinary