CHOLANGICARCINOMA

1. CHOLANGIOCARCINOMA
Dr Lalit K Shah
Resident 1st year
General Surgery
Moderator- Dr Mahipendra Tiwari

2. INTRODUCTION
• Cholangiocarcinoma are tumor originating from bile duct
epithelium
• It is a rare malignancy with overall annual incidence is 1–
1.5 per 100000
• The peak incidence in the 8th decade
• The male:female ratio is approximately 1.5:1

3. CLASSIFICATION
• Cholangiocarcinomas are
classified into three groups
according to their
anatomical location:
(1) intrahepatic(iCCA, 10%)
(2) perihilar(pCCA, 50%)
(3) distal(dCCA, 40%)

4. CLASSIFICATION
• Anatomically, tumours involving the biliary confluence
(hilar cholangiocarcinoma or Klatskin tumours) account
for 60% of cases, with the remainder involving the distal
bile duct (20–30%) or intrahepatic ducts (10–20%)
• Histological Types
1. Diffuse infiltrative/sclerosing
2. Nodular/mass forming
3. Papillary

5. • It can also be classified as
1. Extra-hepatic: divided into perihilar(including confluence
itself) and distal segments with the transition at the point
where the CBD lies posterior to duodenum
2. Intra-hepatic: originate from either small intra-hepatic
ductules(peripheral cholangiocarcinoma) or large intra-
hepatic duct proximal to the bifurcation of right and left
hepatic ducts

6. EPIDEMIOLOGY
• In the United States- 1 to 2 cases per 100000 population
• 3% of all G.I malignancy
• The high prevalence in Asian descent is attributable to
endemic chronic parasitic infestation
• Intra-hepatic variety has been rising over last two
decades in Europe, N America, Asia, Australia and Extra-
hepatic variety are declining internationally
(Patel T. Hepatology 2001;33:1353, Welzel TM et al
2006:98:873, Jespen P et al)

7. RISK FACTORS
1. Chronic inflammatory conditions
• Primary sclerosing cholangitis (PSC)
• Oriental cholangiohepatitis
• Hepatitis C infection
2. Parasitic infections
• Opisthorchis viverrini
• Clonorchis sinensis

8. RISK FACTORS
3. Congenital
• Choledochal cysts
• Caroli’s disease
4. Chemical agents
• Thorium dioxide (Thorotrast); Vinyl chloride; Dioxin;
Asbestos
5. Post surgical
• Biliary–enteric anastomosis

9. • In Western countries, PSC is the most important risk
factor; indeed, approximately 30% of cases of
cholangiocarcinoma in the West are diagnosed in patients
with PSC
• Among patients with PSC, the estimated lifetime
incidence of cholangiocarcinoma ranges from 5% to 10%,
with approximately 50% of these cases being diagnosed
within 24 months of the diagnosis of PSC

10. • In Asian countries, infestation with the liver flukes
Opisthorchis viverrini or Clonorchis sinensis and
hepatolithiasis are important risk factors for
cholangiocarcinoma
• Cirrhosis and hepatitis B or C viral infection have recently
been recognized as important etiologic factors, especially
for intrahepatic cases.

11. Pathology
• While there are several similarities in the pathogenesis
and pathology of iCCA, pCCA, and dCCA, there are also
notable differences
• Genetic analyses comparing iCCAs to the other two types
show that ERBB2/HER2 is less frequently altered in
iCCAs, whereas genes of the FGF pathway are more
frequently altered

12. • SMAD4 may also be less frequently altered in iCCA
• Alterations in K-ras, p53 and P16INK4A are prevalent in
all cholangiocarcinomas
• The most notable genetic difference between iCCAs and
the other types involves mutations in isocitrate
dehydrogenase 1 and 2 (IDH1/2), which occur in
approximately 20% of iCCAs and are generally not found
in other types of cholangiocarcinomas

13. • Even the cell of origin may differ between iCCAs and the
other types of cholangiocarcinoma
• While it was previously suspected that all
cholangiocarcinomas result from the transformation of
cells of bile duct epithelium (cholangiocytes)
• It has recently been shown that this may not always be
the case for iCCA and Liver cells (hepatocytes,
hepatoblasts, and hepatic progenitor cells) can give rise

14. CLINICAL PRESENTATION
• Cholangiocarcnomas become symptomatic when the
tumor obstructs the biliary drainage system, causing
painless jaundice
• Common symptoms
-Pruritis-66%
-Abdominal pain-30-50%
-Weight loss-30-50%
-Fever

15. • Signs
-Jaundice-90%
-Hepatomegaly-25-40%
-Right upper quadrant mass-10%

16. INTRAHEPATIC EXTRAHEPATIC
Late presentation Jaundice
Fever Signs of biliary obstruction
Weight Loss Imaging suggestive of bile duct obstruction
Abdominal Pain
Incidental Finding of isolated hepatic mass

17. INVESTIGATIONS
1. LFT
elevated both total and direct bilirubin
2-10 fold increase ALP
SGOT,SGPT initially normal, elevated in chronic biliary
obstruction

18. 2. Tumor marker
CEA(>5.2 ng/ml- sensitivity 68%, specificity 82%)
CA 19.9
-without cholangitis or cholestasis cutoff >37U/ml- sensitivity
78%, specificity 83%
-presence of cholangitis or cholestasis cutoff >300U/ml
(kim HJ et al Am J Gastroenterol)
Combine CEA + CA 19.9

19. 3. USG
Transabdominal USG is a useful first study for evaluating
obstructive jaundice
It can reveal dilation of the biliary tree
Klatskin: segmental dilation and non-union of RHD and
LHD
Distal cholangiocarcinoma: stricture, polypoid mass, GB
distended

21. 4. CECT
useful for detection of intra-hepatic tumors, biliary
obstruction, liver atrophy
Klatskin tumor- ductal dilation, non-union of RHD and
LHD +/- thickened wall
Triphasic CECT:
-arterial and portal venous phase: hypoenhancing soft
tissue infiltration with mass forming hypovascular lesion
with peripheral rim enhancement
-delayed phase: central rim enhancement

22. evaluation of resectibility: extent of vascular involvement,
biliary anatomy, vascular anatomy and relation of tumor

24. 5. MRCP
non-invasive technique for evaluation of duct system
not require contrast material
delineates extent of biliary involvement
helpful for resection margin

25. 6. Cholangiography(ERCP or PTC)
Preoperative cholangiography is diagnostic or therapeutic
in biliary obstruction
MRCP+ CT replaced invasive chloangiography in
obstructive jaundice due to proximal lesion but still
cholangiography is indicated in
-distal obstruction
-tissue diagnosis
-pre-operative biliary drainage is needed

26. • ERCP vs PTC
-ERCP preffered in PSC as stricturing of intra-hepatic
biliary tree makes PTC difficult
-PTC preferred for imaging of proximal biliary system if
complete obstruction of distal biliary tree

28. 7. EUS
Done if CBD dilated but no mass is seen in CT/MRI
EUS plus FNAB has more sensitivity in distal tumors than
ERCP+ brush cytology
In proximal tumor its role is uncertain

29. 8. PET Scan
Helps in identifying occult metastases, nodal involvement

30. • Staging Laparoscopy
peroitoneal or liver metastasis 20-40% cases at surgical
exploration
to avoid morbidity of unnecessary laparotomy

31. STAGING
• Bismuth-Corlette Classification(Hilar cholangicarcinoma)
• MSKCC Classification
• AJCC

32. Bismuth-Corlette Classification
Doesn’t include vascular encasement, LN involvement, liver atrophy and distant metastasis

33. MSKCC Classification
It takes into account extent of bile duct involvement as well as vascular invasion and hepatic atrophy, may
help determine both the resectability for the tumor and the necessary surgical procedure

34. AJCC

37. Biliary Drainage
• Role of pre-operative biliary drainage
benefits vs drawback
Available retrospective data and one recently reported
multicenter randomized controlled trial (DRainage vs
OPeration [DROP] trial) suggest that among patients
undergoing pancreaticoduodenectomy for periampullary
cancers, routine preoperative biliary stenting is
associated with increased perioperative morbidity rates,
especially with respect to infectious complications

38. Some authors believe stents placed preoperatively make
intraoperative assessment of tumor extent more difficult
However, as liver resection is indicated for most patients
with pCCA, there is concern about postoperative hepatic
insufficiency due to the potentially impaired ability of the
remnant liver to regenerate if biliary flow from that
segment was obstructed preoperatively

39. First, as a potential benefit of drainage is the relief of
obstruction in the portion of liver that will need to
regenerate after resection, drainage of the FLR as
opposed to the liver to be resected is preferred
Second, it should be kept in mind that the patient may be
found to be unresectable on exploration, so drainage
should be planned according to the general principles for
palliating hilar biliary obstruction

40. TREATMENT
Unresectability
Distal
• Medically unfit patient
• Distant metastatic disease
distant metastases(liver + other organ)
Lymph node metastases beyond PV, HA, peripancreatic
• Major vascular involvement
significant portal/SMV
Superior mesentric artery
Common or proper hepatic artery

41. Peripheral or Hilar
• Medically unfit patient
• Distant metastatic disease
hepatic metastases
Lymph node metastases beyond PV, HA, peripancreatic
and celiac axis distribution
• Extensive Local involvement
B/L(or C/L) involvement of PV, HA, secondary biliary
radicals

42. • Inadequate future liver remnant
<30% FLR in patient with normal(non atrophied) hepatic
parenchyma
<2 contiguous segments with adequate portal venous and
hepatic arterial inflow, adequate hepatic venous drainage
and adequate biliary drainage

43. Principles Of Surgery
• complete resection with negative margin
• regional lymphadenectomy(porta hepatis)

44. Distal Cholangiocarcinoma
• Treated with pancreatico-duodenectomy
• A pylorus preserving operation is preferable and feasible
• Because these lesions tend to grow in a submucosal plane,
a frozen section of the proximal bile duct margin helps
ensure an R0 resection
• An R0 resection remains one of the most important
prognostic factors for this disease, with 5-year survival
rates of up to 50% in node-negative patients with an R0
resection

45. Hilar Cholangiocarcinoma
• Type 1 and 2
CBD resection and cholecystectomy
5-10 mm margin of resection
resection of the bile duct and nodal tissue requires
skeletonization of hepatic artery and portal vein
Indications of partial hepatectomy
-U/L second order biliary radicle involvement
-ipsilateral portal vein involvement

46. • Type 3 and 4
-complex hepatic resections
-trisectionectomy
• An extensive neoadjuvant therapy protocol followed by
transplantation has shown promising results in tightly
controlled trials where hilar cholangiocarcinoma occurs in
the setting of underlying liver disease.

48. • Reconstruction
resection and reconstruction of
PV and/or HA may be
necessary for complete
resection
Biliary reconstruction(Roux-en-
Y hepaticojejunostomy

49. • Post resection status

50. • Principles of systemic therapy
primary treatment for unresectable and metastatic
disease-preferred regimen is Gemcitabine+cisplatin
subsequent line therapy for cancers if progression is
FOLFOX or FOLFIRI
• surveilance for R0 and R1 resection
consider imaging every 3 to 6 months for 2 years
every 6-12 months for upto 5 years or as clinically
indicated

51. Intrahepatic Cholangiocarcinoma

55. REFERENCES
• Sabiston Textbook Of Surgery 21st edition
• Bailey & Love 27th edition
• NCCN Guidelines
• Pubmed

56. THANK YOU