Tumors of the Biliary System

Anatomy

Gallbladder Cancer Usually seen in the elderly Diagnosis at advanced stage, unless discovered incidentally during Cholecystectomy (1%) Poor prognosis: 5-38% 5 Yr. Survival Usually unresctable at diagnosis

Incidence 5 th common GI Malignancy 5,000 Diagnosed Annually in the US M:F Ration 1:2-3 75% Diagnosed Above age 65 Prevalence higher in different ethnic groups (e.g. higher in Native Americans) Higher Prevalence of Gallstones!

Etiology Gallstones Anomalous Pancreato Biliary Junction Porcelain Gallbladder Choledochal Cysts PSC Obesity Salmonella Typhi Infection

Porcelain Gallbladder

Pathology And Staging Adenocarcinoma – 90% Less Frequent SCC Oat Cell Carcinoma Undifferentiated Adenosquamatous Carcinoid

TMN Staging Stage Invasion to Lamina PropriaT1a Invasion to Muscular LayerT1b Invasion to Perimuscular connective tissue T2 Peforation of the serosa and/or invasion of the liver and/or invasion of other adjacent organ T3 Invasion to Portal Vein or Hepatic Artery or Multiple extrahepatic organs T4

TMN Staging T1 N0 M0 T2 N0 M0 Stage IA Stage IB T3 N0 M0 T1/T2/T3 N1 M0 Stage IIA Stage IIB T4 Nx M0Stage III Tx Nx M1Stage IV

Clinical Presentation RUQ Cholecystis – Acute, Chronic Cholelithiasis Weight Loss Jaundice Abdominal Mass Less common presentation

DD Acute/Chronic Cholecystitis Cholelithiasis Pancreatic Cancer Gallbladder Hydrops

The gallbladder is abnormally distended, measuring more than 10 cm long. The gallbladder wall is thin (arrows), and there is echogenic sludge within the lumen. Gallbladder Hydrops

Diagnosis US – First modality in RUQ evaluation Heterogeneous Mass replacing Gallbladder Irregular Gallbladder Wall Sen, % CT – Mass replacing Gallbladder Extension to adjacent organs

Diagnosis MRI Enables differentiation from the adjacent liver Visualization of Biliary Obstruction or Portal Vein encasement Cholangiography – Helps diagnose Jaundiced patients for Gallbladder cancer Typical finding: Long Stricture of CBD

Chlangiogram of cholangiocarcinoma. Arrow points to a filling defect of a tumor

Management Depends on the stage of the tumor T1a, T1b – Diagnosed at Cholecystectomy. 5-yr. survival 85%, 100%, resoectively Tx. – Cholecystectomy Complications in Laparoscopic Approach: –Peritoneal Carcinomatosis –Bile Spillage (associated with poor prognosis)

Management invasion beyond (stages II and III) the gallbladder muscular layer – Increased incidence of Lymph node mtastases Tx. - Extended Cholecystectomy for improved survival compared with residual disease Cystic duct stump involvement: CBD resection with Roux-en-Y anastamosis Liver involvement: at least 2 cm resection beyond palpable or sonographic extent Larger tumors: Extended Hepatectomy

Roux-en-Y Hepaticojejunostomy Roux en Y = End to Side Anastamosis

Management In most cases therapy is palliative Requires a tissue diagnosis Obstructive Jaundice can be managed with placement of a stent, either endoscopically or percutaneously. Pain Can be treated with Percutaneous Celiac Plexus Block Results with chemotherapy are poor

Survival most patients with gallbladder cancer have advanced unresectable disease at the time of presentation. As a result, fewer than 15% of all patients with gallbladder cancer are alive after 5 years Depends on pathologic state at presentation

Cholangiocarcinoma

Originates anywhere along the biliary tree. Most commonly at the hepatic duct bifurcation (60%-80% of cases). The diagnosis of cholangiocarcinoma should be considered in every patient with obstructive jaundice

Incidence 1-2 : 100,000 15% Intrahepatic Over the past two decades in developed countries: Intrahepatic incidence Extrahepatic incidence

Risk Factors Choledochal Cysts PSC Hepatolithiasis Hepatitis B, C Increasing Age (usually 50-70) Small male predominance Common Features: Bile Duct Stones Biliary Stasis Infection

Genetic Syndromes Associated with Cholangiocarcinoma Lynch Syndrome II Multiple Billiary Papilomatosis

Staging and Classification Intrahepatic – Treated like HCC Hilar – Largest group, Treated with Bile Duct resection, preferably partial Hepatectomy Distal – Like other peri ampullary tumors, Pancreaticoduodenostomy

TNM Staging Tis carcinoma in situ T1 tumor invades the subepithelial connective tissue T2 tumor invades peri. bromuscular connective tissue T3 tumor invades adjacent organs.

TNM Staging Tis N0 M0Stage 0 T1 N0 M0Stage I T2 N0 M0Stage II T1/2 N1/2 M0Stage III T3 Nx M0Stage IVA Tx Nx M1Stage IVB

Clinical Presentation Jaundice Distal Cholangiocarcinoma – 90% Intrahepatic Cholangiocarcinmoa– Rarely Jaundiced Less Common symptoms Pruritus Fever Abdominal Pain Fatigue Anorexia, Weight Loss

Lab Tests perihilar and distal cholangiocarcinoma – Bilirubin > 10 mg/dL ASP, CA19-9 Increased CA19-9 = sialylated Lewis (a) antigen, a blood type protein on red blood cell

Imaging Studies Abdominal US/CT Intrahepatic cholangiocarcinomas - easily visualized on CT scans perihilar and distal tumors are often difficult to visualize on ultrasound and standard CT scan ERCP/PTC – to define Biliary anatomy most important feature in determining resectability in patients with perihilar tumors – PTC favored Others – MRI, PET

Management Operative vs. Non-Operative approach Radiologic Criteria for non resectabilty Bilateral hepatic duct involvement up to secondary radicals Bilateral hepatic artery involvement Encasement of the portal vein proximal to its bifurcation Atrophy of one hepatic lobe with contralateral portal vein encasement Atrophy of one hepatic lobe with contralateral biliary radical involvement Distant metastasis

Palliative Approach Biliary drainage – serum bilirubin>10mg/dL PTC preferred in perihilar Cholangiocarcinoma ERCP preferred in distal Cholangiocarcinoma Stents Metallic stents remain patent longer longer than plastic stents and require less manipulations Surgical Roux-en-Y Hepaticojejunostomy

Surgical Approach good-risk patients without evidence of metastatic or locally unresectable disease intraoperatively, more than half are found to have metastases or locally unresectable disease »Use of Laparoscopy can may avoid unnecessary Laparotomy

Distal Cholangiocarcinoma Pancreaticoduodenectomy (Whipple's Procedure), Pylorus preserving operation preferred → 5 Ys. Survival – 15-25% If resection os not possible due to vascular involvement Cholecystectomy Roux-en-Y Hepaticojejunostomy Gastrojejunostomy

Intrahepatic Cholangiocarcinoma hepatic resection → 3-ys. survival rates of 22%-66%

Perihilar Cholangiocarcinoma bile duct resection alone leads to high local recurrence rates addition of a modified hepatic resection has improved resectability rates.

Medical Therapy Radiotherapy - survival benefit for local disease Chemotherapy has not been shown to improve survival Combined treatment may be more effective due to sensitization effect

Octcomes Long-term survival dependent on the stage of disease at presentation palliative procedure or complete tumor resection Resection + partial hepatectomy – 5 ys. survival rate > 50% resectable distal bile duct cancer – 5 ys. survival rate of 28% to 45%.