CHOLANGIOCARCINOMACHOLANGIOCARCINOMA

(KLATSKIN TUMOUR)(KLATSKIN TUMOUR)

TR, 84 YRS FEMALE, BG-TR, 84 YRS FEMALE, BG-OSTEOARTHRITIS OSTEOARTHRITIS

Admitted with painless obstructive jaundiceAdmitted with painless obstructive jaundice

Her symptoms were- jaundice, weight loss, Her symptoms were- jaundice, weight loss, anorexia, RUQ discomfort, heart burn, and anorexia, RUQ discomfort, heart burn, and changes in stool and urine colour.changes in stool and urine colour.

She was clinically jaundiced with a non tender She was clinically jaundiced with a non tender palpable gallbladder.palpable gallbladder.

BLOODSBLOODS

Blood- LFT : AST 287, ALT 345, bilirubin 113.5, Blood- LFT : AST 287, ALT 345, bilirubin 113.5,

ALP737, LDH 855, ALP737, LDH 855,

FBC& U/E-NormalFBC& U/E-Normal

INR- 1.0INR- 1.0

Amylase-78Amylase-78

IMAGINGIMAGING CXR & PFA.CXR & PFA.

US US Gallstone, grossly distended GB, Markedly dilated CBD and IHBD.Gallstone, grossly distended GB, Markedly dilated CBD and IHBD.

CT CT - abdomen intra & extra-hepatic bile duct dilatation to the level of the - abdomen intra & extra-hepatic bile duct dilatation to the level of the hepatic hilium. Suggestion of 2cm mass at hilium-?cholangiocarcinoma-hepatic hilium. Suggestion of 2cm mass at hilium-?cholangiocarcinoma-(Klatskin tumour)(Klatskin tumour)

MRCPMRCP-grossly dilated CBD/IHBR, abrupt narrowing of CBD with no -grossly dilated CBD/IHBR, abrupt narrowing of CBD with no obvious filling defect ?cholangiocarcinoma. Grossly distended GB.obvious filling defect ?cholangiocarcinoma. Grossly distended GB.

USS- Gallstone, grossly distended GB, Markedly dilated CBD USS- Gallstone, grossly distended GB, Markedly dilated CBD and IHBD.and IHBD.

CT- abdomen- intra & extra-hepatic bile duct dilatation to the level of the CT- abdomen- intra & extra-hepatic bile duct dilatation to the level of the hepatic hilium. Suggestion of 2cm mass at hilium-?cholangiocarcinoma-hepatic hilium. Suggestion of 2cm mass at hilium-?cholangiocarcinoma-

(Klatskin tumour)(Klatskin tumour)

MRCP-grossly dilated CBD/IHBD, abrupt narrowing of CBD with no MRCP-grossly dilated CBD/IHBD, abrupt narrowing of CBD with no obvious filling defect ?cholangiocarcinoma. Grossly distended GB.obvious filling defect ?cholangiocarcinoma. Grossly distended GB.

ENDOSCOPIC RETROGRADE ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY-CHOLANGIOPANCREATOGRAPHY-

(ERCP).(ERCP).

Performed twice- unsuccessful on both Performed twice- unsuccessful on both occassions.occassions.

PERCUTANEOUS TRANSHEPATIC PERCUTANEOUS TRANSHEPATIC CHOLANGIOGRAPHY (PTC)CHOLANGIOGRAPHY (PTC)

PTC was successfully performed with the PTC was successfully performed with the placement of a metal stent with good result- placement of a metal stent with good result- biliary decompression and relieve of her biliary decompression and relieve of her obstructive symptoms.obstructive symptoms.

KLATSKIN TUMOUR (KT)KLATSKIN TUMOUR (KT)

BG- Bile duct tumours recognized for over a century.BG- Bile duct tumours recognized for over a century. Musser first reported 18 cases of primary extrahepatic Musser first reported 18 cases of primary extrahepatic

biliary cancer.biliary cancer. Sako and colleagues found 570 cases while reviewing Sako and colleagues found 570 cases while reviewing

literature from 1935-1954.literature from 1935-1954. Malignancy of the intrahepatic bile duct was described Malignancy of the intrahepatic bile duct was described

later by Altmeir (1957).later by Altmeir (1957). Gerald Klatskin described cancer of the hepatic duct Gerald Klatskin described cancer of the hepatic duct

bifurcation in 1965 following a review of 13 cases.bifurcation in 1965 following a review of 13 cases. KT tumours are generally small, sharply localized and KT tumours are generally small, sharply localized and

seldom metastasizing.seldom metastasizing.

EpidemiologyEpidemiology Tumours of bile duct are rare-2% of all cancers found at autopsy.Tumours of bile duct are rare-2% of all cancers found at autopsy.

Malignant tumours more common than benign adenomas and Malignant tumours more common than benign adenomas and papillomas.papillomas.

Cholangiocarcinoma most common malignancy of bile ducts, >50%-Cholangiocarcinoma most common malignancy of bile ducts, >50%-Holland et at…2007.Holland et at…2007.

More common in Israel, Japan and American indians More common in Israel, Japan and American indians

Annual incidence of bile duct Ca in USA is 1/100,000 people. Autopsy Annual incidence of bile duct Ca in USA is 1/100,000 people. Autopsy studies show and incidence of 0.01-0.46%. 4,000 new cases reported studies show and incidence of 0.01-0.46%. 4,000 new cases reported annually in USA.annually in USA.

England and Wales - 2.8/100,000 females & 2/100,000 males.England and Wales - 2.8/100,000 females & 2/100,000 males.

ETIOLOGYETIOLOGY Risk factors for bile duct cancer include:Risk factors for bile duct cancer include:

Ulcerative colitisUlcerative colitis

Primary sclerosing cholangitis-10-30%Primary sclerosing cholangitis-10-30%

Parasitic infestations:Liver fluke common in Far East-Parasitic infestations:Liver fluke common in Far East-intrahepatic CC accounts for 20% of primary liver intrahepatic CC accounts for 20% of primary liver tumour.tumour.

Opisthorchis viverrini-found inThailand, and West Opisthorchis viverrini-found inThailand, and West Malaysia.Malaysia.

ETIOLOGYETIOLOGY Toxic chemicals-thorium dioxide (thorotrast), Toxic chemicals-thorium dioxide (thorotrast),

radionuclides, carcinogens-arsenic, nitrosaminesradionuclides, carcinogens-arsenic, nitrosamines

Congenital fibrosis or cysts-cogenital hepatic fibrosis, Congenital fibrosis or cysts-cogenital hepatic fibrosis, cystic dilatation, choledochal cyst, polycystic livercystic dilatation, choledochal cyst, polycystic liver

Drugs: methyldopa, isoniazide, OCP.Drugs: methyldopa, isoniazide, OCP.

Gallstones and hepatolithiasis-decrease incidence >10 Gallstones and hepatolithiasis-decrease incidence >10 years post cholecystectomy.years post cholecystectomy.

Biliary cirrhosis and typhoid carriers.Biliary cirrhosis and typhoid carriers.

PATHOPHYSIOLOGYPATHOPHYSIOLOGY Bile duct tumours cause bile duct obstruction - biliary Bile duct tumours cause bile duct obstruction - biliary

stasis and alteration of liver function testsstasis and alteration of liver function tests

Prolonged obstruction then leads to-Prolonged obstruction then leads to-

Hepatocellular dysfunction, renal dysfunction Hepatocellular dysfunction, renal dysfunction

Progressive malnutrition, Pruritus, coagulopathyProgressive malnutrition, Pruritus, coagulopathy

Cholangitis- esp if previous endoscopic, percutaneous or Cholangitis- esp if previous endoscopic, percutaneous or surgical biliary interventions have been performed.surgical biliary interventions have been performed.

Anatomically, biliary tree is divided into 3 parts, upper 3Anatomically, biliary tree is divided into 3 parts, upper 3rdrd-55%, middle -55%, middle 33rdrd 15% and lower 3 15% and lower 3rdrd 10%.Of these tumours, 10% are diffuse. 10%.Of these tumours, 10% are diffuse.

Bismuth Classification Bismuth Classification Type i-involvement of common hepatic duct.Type i-involvement of common hepatic duct.

Type ii-bifurcation involved without involvement of Type ii-bifurcation involved without involvement of secondary intrahepatic duct.secondary intrahepatic duct.

Type iiia-extends into the right secondary intrahepatic Type iiia-extends into the right secondary intrahepatic duct.duct.

Type iiib-extends into the left secondary intrahepatic duct.Type iiib-extends into the left secondary intrahepatic duct.

Type iv- secondary intrahepatic ducts involved on both Type iv- secondary intrahepatic ducts involved on both sides.sides.

PRESENTATIONPRESENTATION CC seen in advanced unresectable stageCC seen in advanced unresectable stage

Early diagnosis unusualEarly diagnosis unusual

Typically elderly- average age 60-65years though Klatskin Typically elderly- average age 60-65years though Klatskin slightly younger age groupslightly younger age group

Abnormal LFTs / Jaundice-90%Abnormal LFTs / Jaundice-90%

Abdominal pain / Weight loss- in (30-50%) of cases -Patel Abdominal pain / Weight loss- in (30-50%) of cases -Patel et al 2006et al 2006

Pruritus seen in 66% of patientsPruritus seen in 66% of patients

PRESENTATIONPRESENTATION Fever- 20%Fever- 20%

Diarrhoea, anorexia, changes in urine & stool Diarrhoea, anorexia, changes in urine & stool colour and weight loss.colour and weight loss.

Liver may be enlarged and smooth-25-40%Liver may be enlarged and smooth-25-40%

Distended and non tender gallbladder 10%Distended and non tender gallbladder 10%

Epigastric tenderness.Epigastric tenderness.

DIAGNOSISDIAGNOSIS History / physical examinationHistory / physical examination

Labouratory-CEA and CA19.9 –sensitivity of 66% and a Labouratory-CEA and CA19.9 –sensitivity of 66% and a specificity of 100% in diagnosing CC in pt with PSC.specificity of 100% in diagnosing CC in pt with PSC.

Imaging-tumours are generally small-USS/ CT may fail to Imaging-tumours are generally small-USS/ CT may fail to show the lesion.show the lesion.

Cholangiography via a transhepatic or endoscopic Cholangiography via a transhepatic or endoscopic approach reqired to define biliary anatomy and extent of approach reqired to define biliary anatomy and extent of the lesion.the lesion.

DIAGNOSISDIAGNOSIS Cholangiographic appearance of Klatskin tumour is Cholangiographic appearance of Klatskin tumour is

characteristic.characteristic.

PTC preferred over ERCP for demonstrating ductal PTC preferred over ERCP for demonstrating ductal anatomy-PTC-almost 100% sensitivity & specificity.anatomy-PTC-almost 100% sensitivity & specificity.

MRCP non-invasive and now more available.MRCP non-invasive and now more available.

Histology –a well defferentiated adenocarcinoma-short Histology –a well defferentiated adenocarcinoma-short annular constricting lesion 75%, diffusely infiltrating with annular constricting lesion 75%, diffusely infiltrating with long strictures 15%& intraluminal polypoid mass-3-5%long strictures 15%& intraluminal polypoid mass-3-5%

TREATMENTTREATMENT Management challenging with relatively poor prognosis.Management challenging with relatively poor prognosis.

Surgery continues to be the mainstay of therapy with 5year Surgery continues to be the mainstay of therapy with 5year survival of 10-40%.survival of 10-40%.

Complete resection with negative histologic margins –long -Complete resection with negative histologic margins –long -term survival.term survival.

Yang WL et at.. 2007 reported in a study of 185 cases (1972-Yang WL et at.. 2007 reported in a study of 185 cases (1972-2006) a median survival of 37 months following radical 2006) a median survival of 37 months following radical resection, 17months for palliative resection and death within resection, 17months for palliative resection and death within 1.5years if no resection.1.5years if no resection.

Hepatic resection- a critical component of operative approach. Hepatic resection- a critical component of operative approach.

TREATMENTTREATMENT Adjuvant chemoradiotherapy-no benefit.Adjuvant chemoradiotherapy-no benefit.

Liver transplant for unresectable tumour remains Liver transplant for unresectable tumour remains controversial, tumour recurrence >90%.controversial, tumour recurrence >90%.

Advances in interventional Radiology and endoscopy- Advances in interventional Radiology and endoscopy- facilitate non surgical option.facilitate non surgical option.

Benefit of external beam radiotherapy for palliation of Benefit of external beam radiotherapy for palliation of proximal CC uncertain.proximal CC uncertain.

Photodynamic therapy a new palliative treatment modality Photodynamic therapy a new palliative treatment modality for failed stent. Thomas Zoepf et al concluded in a series in for failed stent. Thomas Zoepf et al concluded in a series in 2008 -offers similar survival time as incomplete resection.2008 -offers similar survival time as incomplete resection.

CONCLUSIONCONCLUSION

Klatskin tumour is tumour of bile duct Klatskin tumour is tumour of bile duct bifurcation.bifurcation.

Diagnosis can be quite challenging as Diagnosis can be quite challenging as presentation is in an advanced stage with non-presentation is in an advanced stage with non-specific symptoms.specific symptoms.

Surgery offers the only hope of cure.Surgery offers the only hope of cure.

THANK YOU!THANK YOU!