Gallbladder and Bile Duct Cancer

• Bile duct cancers
• In the USA, primary bile duct cancer occurs at a rate of 1 per 100,000 each year
• 95% epithelial adenocarcinoma (cholangiocarcinoma)
• Ages 50-70
• More common in men
• Often in the extrahepatic bile ducts
• Risk factors
 

Sclerosing cholangitis	*25
Choledochal cyst	*20
Ulcerative colitis	*15
Hepatolithiasis	*6
People of Asian origin (Clonorchis sinensis)	*5
Choledocholithiasis	*4
Thorotrast	*4
White race	*2
Male	*1.5

* Compared with the healthy population

• The most common histological type is adenocarcinoma 95% (papillary, nodular, diffuse),
• Tumors seen in the middle third (17%) and distal third (18%) have a better prognosis than tumors of the proximal third (58).
• Local and lymphatic spread are seen more often.

DIAGNOSIS

• Clinical
• Physical examination
• Biochemistry
• Radiology
• Clinical
• 90% painless jaundice
• Fatigue
• Loss of appetite
• Nonspecific abdominal discomfort
• Fever and pain (if cholangitis develops)
• Physical examination
• Mild hepatomegaly
• Hydropic gallbladder (distal tumor) -> Courvoisier sign
• Acholic stools and dark urine
• Severe itching
• Portal hypertension and splenomegaly in advanced cases obstructing the portal vein
• Biochemistry
• Increase in bilirubin, ALP and GGT values.
• Nonspecific laboratory findings
• CA 19-9
• Radiology
• US
• CT
• MRCP
• PTC
• ERCP
• Late-phase splenoportography with celiac arteriography
• Doppler USG
• Staging of bile duct cancer (AJCC-TNM)
• TNM
• T 1 -> Limited to the bile duct mucosa or muscle layer
• T 2 -> Invasion of periductal tissue
• T 3 -> Invasion of adjacent structures
• N 0 -> No regional lymph node involvement
• N 1 -> Regional lymph node involvement (hepatoduodenal ligament)
• N2  ->Peripancreatic, periduodenal, periportal, celiac
• M 0 -> No distant metastasis
• M 1 -> Distant metastasis present

• Bismuth – Corlette

• Resectability
• Bilateral or multifocal intrahepatic spread on cholangiography
• Involvement of the main portal vein
• Bilateral involvement of the hepatic arterial or portal venous structures
• Patient-related factors (advanced comorbid disease, cirrhosis and portal hypertension)
• Distant mets (liver, lung, peritoneum or N2 lymph node mets);
if present, the tumor is considered unresectable.
• Resectability
• Staging laparoscopy may be performed to identify lymphatic and occult peritoneal spread that cannot be shown by preoperative studies before laparotomy. Laparoscopic US is a highly sensitive method for precisely visualizing the involved bile ducts and the surrounding anatomy.
• RESECTABILITY
• Serial US, CT and antegrade or retrograde cholangiography show the location, size and spread of bile duct cancers causing obstruction.
• If a resectable tumor is found in these studies, the next step is to determine the tumor's local vascular involvement.
• Resectability (Pre-op)
• Percutaneous transhepatic cholangioscopy (PTCS) performed preoperatively to precisely define the boundaries of the tumor located in the intrahepatic bile ducts and to plan the resection margins
• Portal vein embolization on the diseased side preoperatively to achieve hypertrophy of the tumor-free side (Nimura)
• TREATMENT
• Curative resection
• Palliative resection
• Adjuvant
• Surgery
In patients with bile duct cancer, surgical resection with negative margins is the only chance of cure. The extent of resection is determined directly by the tumor's location and regional invasion.
Before surgery, the patient's metabolic disorders and coagulation disorders must be treated.
• Surgery
• Distal third --> Whipple procedure
• Middle third --> Resection and Roux-en-Y hepaticojejunostomy
• Proximal third --> Resection and Roux-en-Y hepaticojejunostomy (bilateral), if necessary liver resection and caudate lobectomy
• Palliation
In patients with unresectable cholangiocarcinoma, palliation is needed to minimize the symptoms of biliary obstruction.
• Nonoperative palliation
• Operative palliation
• Nonoperative palliation
Biliary drainage tubes that can be placed percutaneously or endoscopically are used. Both ductal systems must be drained effectively, regardless of the location of the tumor.
• Plastic stents
• Metal stents
• Operative palliation
• Biliary-enteric bypass with or without stents
• Internal anastomosis to a major hepatic duct (often a segment III bypass)
• Adjuvant therapy
• No effect on survival
• RT
• CT (5-FU, Mitomycin-C and cisplatin)
• Brachytherapy (internal radiotherapy with iridium wires)
• Clinical results
• Gallbladder cancers
• They are seen 3-4 times more often in women than in men.
• The fifth most common tumor of the GI tract
• Gallbladder cancer has been found in 1% of patients who undergo cholecystectomy for symptomatic cholelithiasis.
• Stones accompany 90% of gallbladder cancers.
• Risk
• Stones
• Porcelain gallbladder
• Adenomatous polyps
• Chronic typhoid carriage
• Diagnosis
• It is an aggressive tumor characterized by early metastasis and a rapid clinical course.
• In symptomatic patients, the tumor is already at an advanced stage when diagnosed.
• Symptoms are similar to those of benign gallbladder diseases.
• Clinical
• Right upper quadrant pain
• Loss of appetite, nausea
• Intolerance to fatty foods
• Fever, chills
• Weight loss
• Jaundice, itching
• It may present as acute cholecystitis.
• Physical examination
• Tenderness or a mass in the epigastric region or right upper quadrant
• Hepatomegaly
• Jaundice
• Ascites
• Biochemistry
• Nonspecific findings: leukocytosis, anemia, raised sedimentation rate, low albumin, etc.)
• Increase in liver function test values
• Coagulation disorder in advanced cases
• Radiology
• US
• CT
• MRCP
• ERCP
• STAGING
• TNM
• T is --> Carcinoma in situ
• T 1 --> Mucosal involvement
• T 2 --> Involvement of perimuscular connective tissue
• T 3 --> Extends beyond the serosa or involves one adjacent organ
• T 4 --> Tumor extends more than 2 cm into the liver or involves 2 or more adjacent organs
• N 0 --> No lymph node mets
• N 1 --> Mets to cystic duct, pericholedochal and/or hilar lymph nodes
• N 2 --> Mets to peripancreatic, periduodenal, celiac and/or superior mesenteric lymph nodes
• M 0 --> No distant mets
• M 1 --> Distant mets present
• Histology
• 90% adenocarcinoma (papillary, nodular, papillary infiltrative and nodular infiltrative)
• 10% squamous or adenosquamous
• Spread
• Local spread is the most common. 65-95% have liver involvement.
• Venous spread: Into the liver along the gallbladder bed
• Lymphatic spread: To the cystic, pericholedochal, periportal, hilar, peripancreatic, periduodenal, celiac, SMA and para-aortic lymph nodes
• Nevin classification
STAGE
I --> Limited to the mucosa
II --> Mucosa and muscularis mucosae
III --> Mucosa, muscularis and subserosa
IV --> Local invasion or metastasis
• Most patients are caught at stage 4-5, which worsens the prognosis.
• Treatment
• Surgery
• CT (postoperative adjuvant)
• RT (postoperative adjuvant)
• Palliation
• Surgery
• Stage I -> Cholecystectomy
• Stage II-III -> T2,3,N0 Extended cholecystectomy (resection of segments 4 and 5 together with N1 and N2 lymph node dissection)
• T4 N0 patient: Right trisegmentectomy and lymph node dissection
• N1 patient: Right trisegmentectomy and bile duct resection
• N2 or M1 patient --> Palliation
In stage I patients
• Patients after cholecystectomy:
• T1 (clear margins): no additional treatment needed
• T1 (tumor at the cystic duct margin): resection of the cystic duct.
• T2,3: Right trisegmentectomy, lymph node dissection, and removal of the port sites.
• N2 or M1 patient: palliation