CHOLANGIOCARCINOMA

:
IS IT REAL PROBLEM IN
INDONESIA?
DR. dr. Rino A. Gani, SpPD-KGEH

INTRODUCTION
Cholangiocarcinoma (CCA) is the second most

common primary hepatic malignancy worldwide

1st
Hepatocellular
Carcinoma (HCC)

2st
Cholangiocarcinoma

INTRODUCTION
About

two-thirds are
located at the hepatic
duct bifurcation (60%80% of cases)

CCA

should be considered in patients with underlying

hepatolithiasis or PSC with worsening performance status,
unexplained loss of weight, or failure to thrive

INTRODUCTION
Most CCA present with jaundice and the diagnosis of

CCA should be considered in every patient with

obstructive jaundice

INTRODUCTION
Most patients with unresectable disease die within a

year of diagnosis
As there are no specific symptoms in early malignant

lesions, patients with CCA mostly present in the

advanced stages of the disease, which contributes to
its poor prognosis
CCA should be sub-classified as intrahepatic (iCCA),

perihilar (pCCA), or distal (dCCA) where iCCA arises

within the liver parenchyme

EPIDEMIOLOGY

Globally, CCA is the second most common primary hepatic malignancy, with

a reported incidence of one to two cases per 100.000 in the USA

EPIDEMIOLOGY

The incidence of CCA increases with age, and the

majority of patients are 65 years and older

EPIDEMIOLOGY

EPIDEMIOLOGY
In Indonesia, data from RSCM during 2010 until 2014

of 758 patients with obstructive jaundice obtained 402

patients with malignant cases and 356 patients with
benign cases. The most common cause of malignant
cases is carcinoma of the ampula vater (17,1%),
pancreatic cancer (55,8%), and followed by
cholangiocarcinoma (19,3%)

RISK FACTORS OF iCCA

Risk factors of iCCA has similar risk factors to HCC,
including cirrhosis, chronic viral hepatitis, alcohol
excess, diabetes, and obesity, which suggests
common pathobiological pathways to all primary liver
parenchymal tumors

Signaling pathways and molecular therapies in iCCA

GENETIC ALTERATIONS IN iCCA

Mutations
Copy number variastions
Protein fusions
Epigenome changes
Signaling pathways activated in iCCA
IL6-STAT3 pathway
EGFR signaling

Hepatocyte growth factor/ Met signaling

Molecular classification of iCCA

CLASSIFICATION

CLINICAL DIAGNOSIS OF
iCCA
Clinical Presentation
Non-specific and insufficient to establish a diagnosis
Patients with early stage usually asymptomatic

 At more advanced stages

Jaundice

Weight loss
Malaise
Fever
Abdominal discomfort
Hepatomegaly
Palpable abdominal mass
Biliary tract obstruction

(infrequently)

Pathologic Diagnosis
A pathological diagnosis of iCCA is based on the WHO

classification of biliary tract cancer

adenocarcinoma or mucinous carcinoma

showing

an

The most common histological findings of an iCCA are

those of an adenocarcinoma showing tubular and/or

papillary structures and a variable fibrous stroma
The sensitivity of liver biopsy for pathological diagnosis

will depend upon location, size, and operator expertise

Imaging
CT scanning
MRI
Fluorodeoxyglucose

(FDG-PET)
Ultrasonography

positron emission tomography

Tumor Markers
Tumor markers in serum or bile are not specific for

iCCA but may be of diagnostic value

Current tumor markers such as Carbohydrate Antigen

(CA) 19-9 and carcinoembryonic antigen have

significant overlap with other benign diseases and low
sensitivity for early stage disease which limit their use
for diagnosis

Genetic Biomarkers
Recent studies have identified mRNA and non-coding

RNA expression that are associated with iCCA

Assessment of disease extent

Radiological studies are necessary for assessment of

the extent of local-regional, or distant spread, staging,

and resectability

TREATMENT

A suggested treatment algorithm for patients with iCCA

RECOMMENDATIONS
Surgical resection is the treatment of choice for iCCA
Patients with iCCA with single intrahepatic nodules
and no evidence of disease desemination are optimal
candidates for resection. Patients demonstrating
intrahepatic metastases, vascular invasion or obvious
lymph node metastases should not undergo resection
Staging laparascopy cant be universally endorsed in
the staging of iCCA

RECOMMENDATIONS
Lymphadenectomy of regional nodes is recommended
given its prognostic value
In cirrhotic patients, advanced liver failure precludes
surgical resection
There is no established adjuvant therapy after
resection