Cholangiocarcinoma : Is It Real Problem in Indonesia?

Cholangiocarcinoma : Is It Real Problem in Indonesia?DR. dr. Rino A. Gani, SpPD-KGEHINTRODUCTIONCholangiocarcinoma (CCA) is the second most common primary hepatic malignancy worldwide

1st Hepatocellular Carcinoma (HCC)2st CholangiocarcinomaAbout two-thirds are located at the hepatic duct bifurcation (60%-80% of cases)

INTRODUCTIONCCA should be considered in patients with underlying hepatolithiasis or PSC with worsening performance status, unexplained loss of weight, or failure to thrive

Most CCA present with jaundice and the diagnosis of CCA should be considered in every patient with obstructive jaundice

INTRODUCTIONMost 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

INTRODUCTIONEPIDEMIOLOGYGlobally, CCA is the second most common primary hepatic malignancy, with a reported incidence of one to two cases per 100.000 in the USA

The incidence of CCA increases with age, and the majority of patients are 65 years and older

EPIDEMIOLOGY

EPIDEMIOLOGYIn 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%) EPIDEMIOLOGYRISK 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 iCCAGENETIC 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 signalingMolecular classification of iCCAClassification

CLINICAL DIAGNOSIS OF iCCAClinical Presentation

Non-specific and insufficient to establish a diagnosis

Patients with early stage usually asymptomatic

At more advanced stagesJaundiceWeight lossMalaiseFeverAbdominal discomfortHepatomegalyPalpable abdominal massBiliary tract obstruction (infrequently)

Pathologic Diagnosis

A pathological diagnosis of iCCA is based on the WHO classification of biliary tract cancer showing an adenocarcinoma or mucinous carcinoma

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 scanningMRIFluorodeoxyglucose positron emission tomography (FDG-PET)Ultrasonography

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 extentRadiological 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 iCCARECOMMENDATIONSSurgical 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 iCCARECOMMENDATIONSLymphadenectomy 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