surgical oncology , SMS JAIPUR

1. Dr. Naina
SR1 Surgical oncology
SMS Medical College and Hospital, Jaipur
CholangioCarcinoma
18.06.2021

2. Anatomy
Applied pointers
• Common bile duct is 5 to 15 cm long.
• The supra duodenal portion of the common bile
duct has been shown to contain scattered bundles
of smooth-muscle arranged in a longitudinal
direction. The muscle is very weak and contraction
of the muscle is an unlikely cause of biliary colic.
• The union of the common bile duct and the
pancreatic duct forms the ampulla of vater
however an actual widening of the lumen as
suggested by the term ampulla will occurs in only
about 5% of cases. A normal papilla will permit the
passage of a dilator 3MM in diameter.

3. Vascular supply of CBD:
• Major Contributor is posterior superior pancreatico duodenal artery assisted by the hepatic and
cystic artery. The blood supply to the CBD may be relevant in stricture formation of the duct which
may occur following apparently minimal trauma to the duct and following liver transplantation.
• There is a vascular plexus around, in the wall of, and in the course of the common bile duct.
Branches of the Gastro duodenal artery runs on the sides of CBD at the 3 and 9 o’clock positions.
The GDA also supplies the retro pancreatic portion of the CBD. A retro portal artery which may
arise from either the coeliac axis or the SMA, runs behind the head of pancreas and posterior to
the portal vein to reach the posterior aspect of the CBD.
• It is recommended that minimal dissection be done around the CBD particularly at the sides of the
duct.
• In mobilising the duodenum and head of pancreas a thin fibrous layer on the back of head of
pancreas and portal vein should be left intact to protect the retro portal artery.

5. • The proximity of the portal vein and hepatic artery to the bile duct in the hilum leads to early
vessel involvement or occlusion from Peri hilar CCA, which affects the options for surgical
resection.
• The lymph nodal drainage of the bile ducts involves the superior pancreaticoduodenal, retro
portal, or proper hepatic nodes first and then the Peri pancreatic, coeliac and Intra aortocaval
lymph nodes.
• Lymph nodes in the ports hepatis may be difficult to remove because of attached venous
branches from the portal vein or fixation of tumour involved lymph nodes to the bile duct,
portal vein, hepatic artery or the head of pancreas.
• A multi institutional cohort study reported that the presence of lymph-node metastasis
significantly and adversely affects patient survival and explains the survival benefit of a
Lymphadenectomy for iCCA.

6. Types of Cholangiocarcinoma
• Intrahepatic CCAs arise from the Intra
hepatic biliary tract beyond the second
order ducts.
• Distal extra hepatic CCAs arise from the
common hepatic duct extending up to the
junction with the cystic duct up till the
papilla.
• Peri hilar CCA arise from the second order
ductal division within the liver and the large
extra cellular ducts up to the confluence
with the cystic duct. Most common type

8. • A preoperative clinical staging system that accurately assesses resectability
would be of value clinically. Such a classification, the Blumgart staging
system, has been proposed that is based upon biliary tumor extent, the
presence or absence of portal vein involvement, and the presence or absence
of hepatic lobar hypertrophy.

9. Etiology
• Opisthorchis viverrini and Clonorchis sinensis. - associated with ingestion of
raw fish containing the larva of liver fluke. Infestation is reversible with
praziquantel. Degree is measured by stool count and is related to the risk for
CCA. Infestation is associated with intra hepatic stones as well as with
elevated nitrates, and studies suggest that nitroso compounds may be
involved in carcinogenesis.
• HIV, HBV, HCV infections increase risk of iCCA.

10. • In 5 to 10% of patients with PSC : Occurs more frequently in patients with
chronic ulcerative colitis than in the general population. Characterised by
inflammation within the biliary tract and subsequent development of diffuse
multifocal biliary duct strictures. The presence of underlying liver
dysfunction resulting from biliary tract disease complicates surgery or
chemotherapy.
• Hepatolithiasis : In Southeast Asia, chronic portal bacterimia and portal
phlebitis are associated with intrahepatic pigmented stones and subsequently
increased risk of CCA. Cancers may develop even after stone removal
potentially related to stasis and cholangitis related to fibrosis induced by stone
disease.
• Anomalous Pancreatic biliary duct junction ( APBJ) may lead to chronic
inflammatory state in the bile duct – increased risk of CCA.

11. • In 10 to 20% of patients with choledochal cyst CCA will develop if left on treated or managed
with surgical drainage alone. Early excision reduces the risk of CCA. Caroli disease is a rare
variant of Choledochal cyst that results in intrahepatic ductal dilatation and an increased risk
of developing CCA.
• Occupational exposure to asbestos and volatile compounds in printing industry like 1,2 Di
chloro propane may also increase the risk of CCA.
• Thorotrast is a vascular contrast agent used earlier – associated with an increased risk of
cancer.
• Risk associated with cigarette smoking not well quantified.
• Liver cirrhosis is a risk factor for ICCA. Risk factors for cirrhosis such as chronic HCV, chronic
HBV and alcohol are also associated with higher risk for iCCA.

12. Pathology
Gross morphology
• Exophytic ,nodular mass forming, Intra ductal, periductal infiltrating ( sclerosing)
• Sclerosing type associated with an intense desmoplastic reaction and often manifests
as diffuse thickening of the ducts without a defined mass.
• The nodular type tends to result in a mass lesion and usually arises within the liver.
• Intraductal type are less common and can encompass a range of lesions from pre-
neoplastic to invasive carcinomas.
• In some patients dCCA may present only as a thickened bile duct wall involved in a
dense fibrous scar.
• Polyploid or capillary cancers have the best prognosis. Papillary cancers represent a
low-grade Adeno carcinoma that is represented by a polyploid mass filling the lumen
of the bile duct with minimal invasion and no desmoplastic reaction.

13. Histology
• More than 90% are epithelial adenocarcinomas.
• Other variants are well differentiated, pleomorphic, giant cell, adeno squamous, oat cell and colloid
carcinomas.
• Sclerosing tumours are characterised by an extensive fibrous stroma with interspersed tumour
cells.
• Papillary tumours may have papillary fronds with extension into the bile duct lumen and may
produce extra cellular mucin.
• Nodular mass forming tumours may vary with appearances akin to sclerosing type or with tubular
pattern.
• Satellites are common and may result from spread along the bile ducts or from vascular invasion
and Intrahepatic metastatic spread.
• Regional lymph node meta stasis and perineural invasion are common with PCCA and DCCA.
Distant metastasis occur but are unusual.

14. • IDH1/2 Mutations are not seen with PCCA or DCCA but may occur in UpTo
25% of ICCA whereas KRAS mutations are more common in the former.
• FGFR2 Fusions are seen virtually exclusively in ICCA in upto 45%of cases.
• Her 2 neu Occur alterations occur largely in gallbladder and DCCA.

15. _—

19. DD between iCCA AND HCC:
• Intra hepatic CCA can be distinguished from HCC by slow uptake of contrast,
particularly in highly desmoplastic tumours and a peripheral rim of enhancement.
MuCIN production ,fibrosis between the acini of tumour tissue and a more overtly
glandular pattern other main differentiating characteristics from HCC.
• Unlike HCC, some CCA stain positively for cancer antigen 199 or CEA or alpha V
beta six INTEGRIN, but not for hepatocyte antigen.
• It may be difficult to distinguish ICCA from a liver metastasis of extrahepatic origin
if a cytology can analysis shows adenocarcinoma. Cytokeratin 7 or cytokeratin 20
maybe helpful to establish a biliary origin. CK 20 is focal and rare in ICCA in
contrast to being diffuse and common in colorectal cancer metastasis. If a primary
site cannot be identified a diagnosis of ICCA should be presumed.

20. Surgery for iCCA
• Resectibility rate 32-90%
• Mortality <10%
• Prognostic factors include lymph-node metastasis, positive margin status, vascular
invasion, satellite metastasis, tumour size, CA1 99 level more than 1000.
• Intrahepatic intraductal papillary tumours have an excellent prognosis if completely
resected.
• Median survival after surgical resection is 36 months
• Five-year survival with R0 is approximately 60% but curative resection is possible
only in about 30%.

21. • There is high risk of tumour recurrence both locally with intrahepatic
metastasis as well as with extrahepatic disease.
• Surgery is generally not indicated for recurrent CCA.
• Liver transplant 5 year survival 29% therefore not generally offered.
• IDH1 and IDH2 more commonly identified mutations in ICCA.

26. Perihilar CCA:
• PCCA are less accessible than other distal CCA for sampling. The highly
desmoplastic nature of these tumours further limits the amount of cellular
material that may be obtained for a cytologic analysis.
• Benign disease noted in about 10% of surgical resections performed for
presumed PCCA. A positive diagnosis with brush cytology ranges from 44% to
80%.
• Mucobilia on ERCP is an uncommon finding that is highly suggestive of a
papillary CCA. Papillary tumours could be either intrahepatic or extrahepatic.
Fnac is also useful if a mass can be seen on US examination or on CT scan.

27. Perihilar CCA:
• Recent studies have shown that bilateral second order duct extension does not affect
prognosis, independent of nodal metastasis and vascular invasion.
• The presence of extra hepatic nodal disease or metastasis is a contraindication to transplant.
In carefully selected patients,a multi modality approach combining preoperative CTRT,
staging laparoscopy, and orthotropic liver transplantation has resulted in overall five-year
survival rates of up to 82%.
• Outcomes better in PSC with 72% five-year survival compared with 51% in non-PSC
patients.if liver transplant is being considered As a treatment option, fna of the hilar lesion by
EUS should be avoided because of the risk of tumour seeding.
• It may be appropriate if a hemihepatectomy for CCA is planned in a jaundice patient or if a
pancreatico duodenectomy is to be done in a patient with long-standing or severe jaundice.

28. Surgery for perihilar CCA:
• Excision of the bile ducts maybe possible up to the first order-branches of the
right and left bile duct. If the tumour extends beyond this on one side, a partial
hepatectomy may be needed and a roux en Y reconstruction performed.
• The contralateral preserved bile duct should be transected at the level of the first
segmental branch to maximise the chance of a negative margin. If the resection
is extended beyond the first order branches, a main drainage channel may need
to be fashioned by suturing the individual segmental or sectoral ducts together.
• A caudate lobe resection is often routinely performed because invasion of the
caudate ducts may occur. Several early branches of the left hepatic duct drain in
the caudate lobe and can be involved with the tumour involving the left main
hepatic duct. Indeed 46% of PCCA microscopically involve the caudate lobe.

29. • Bilateral bile duct involvement to the point that all 4 sectional ducts are
involved precludes curative resection.
• Other indicators of unresectibility include bilateral intrahepatic bile duct
spread, involvement of the main trunk of the portal vein, involvement of both
branches of the portal vein or bilateral involvement of hepatic artery and portal
vein, or combination of vascular involvement of one side of liver with extensive
bile duct involvement on the other side. With vascular replacement it may be
possible to resection some tumours previously considered unresectable.

30. • A periportal lymphadenopathy is not a contraindication and resection with r1
determined after resection can provide significant palliation.
• Lymphadenectomy should include all Soft tissue in porta hepatis excluding the
portal vein and hepatic artery. The CHA nodes, the celiac artery nodes , the
Peripancreatic nodes and the interaortocaval lymph-node should be assessed
because dissection may be indicated
• Adequate staging may require sampling of at least seven nodes.
• Desmoplastic nature of these tumours and fibro inflammatory changes related to
presence of biliary stent often restricts an accurate determination of the
presence of tumour in frozen sections.

31. Distal CCA
• In patients with PSC, cut-off of 100 international units for CA 99 has a sensitivity of 89% and specificity
of 86% for CCA in PSC.
• The kings college group index that incorporates both CEA AND CA199 values has attained similar
sensitivities for cancers arising in patients with psc.
• Bile CEA levels are reportedly elevated in CCA but not in benign diseases other than intrahepatic
stones.
• The diagnosis of malignancy patients who have a biliary stricture can be very difficult. Because of the
dense associated stroma, well differentiated cancers with little invasion are difficult to differentiate from
the bile duct that has a fibrotic scar or stricture from PSC or other biliary tract injury.
• The presence of malignant appearing cells within nerve sheets that is perineural invasion is an
important diagnostic criterion of malignancy that is not present in benign stricturing disease such as
PSC.

32. • Cancers of the lower bile duct may not be readily distinguished from ampulla ray,
duodenal or pancreatic cancers. Although all present similar to DCCA, establishing
the diagnosis is helpful because the DCCA are less likely to metastasise widely and
may have a more favourable outcome with aggressive treatment.
• After surgical resection, many patients require pancreatic enzyme replacement and
few develop diabetes.
• Poor prognostic factor - p53Expression, nodal mets, positive margins, pancreatic
invasion and perineural invasion.
• Tumour recurrence may occur locally within the peritoneum or local nodes or with
distant metastasis.

34. PCCA post resection:
• Negative prognostic variables include tumour stage, nodal disease, tumour
grade, BiliRubin concentration, serum albumin level, post-operative sepsis and
presence of Mucobilia.
• Recurrence is most commonly occur locally at the resection bed or within the
retroperitoneal lymph nodes. Distant Mets occur in one third of cases most
commonly within lung (most common), mediastinum, liver or peritoneum.
Routine liver resection maybe indicated.
• Surgery is generally not indicated for the recurrent CCA.

36. Most centers selectively perform nonoperative biliary drainage in patients with
perihilar cholangiocarcinoma who have a serum bilirubin level over 10 mg/dL,
deferring definitive operative intervention until bilirubin levels are less than 2 to 3
mg/dL.

41. Thank you!