Hepatobiliary and Pancreatic Cancer - Copy

Hepatobiliary and Pancreatic Cancer

Epidemiology

• Account for 4% of all new cancer diagnoses

• Cancers with a high mortality rate and accounts for 9% of all cancer-related deaths.

• Worldwide, hepatocellular carcinoma (HCC) is the third most frequent cause of death from cancer

CHOLANGIOCARCINOMA

• This is carcinoma of the cholangiocytes ie cell of the bile ducts.

• 2 forms of cholangiocarcinoma are (1) intrahepatic or mass-forming cancers

(2) ductal cholangiocarcinomas• Symptoms, if present, include abdominal

discomfort, night sweats, low-grade fever, weight loss, and anorexia.

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Lab tests

• Results of liver serum biochemical tests are nonspecific and can even be normal

• Serum tumor markers such as CA 19-9 and carcinoembryonic antigen may be elevated

CT scan

• Compared with HCCs, intrahepatic cholangiocarcinomas on cross-sectional abdominal imaging by CT do not demonstrate the same degree of contrast enhancement during arterial-phase studies.

• Delayed peripheral venous-phase enhancement is common

Pathologic analysis

• These cancers appear as adenocarcinomas and are often mistaken as adenocarcinomas of unclear origin

Ductal carcinomas

• Often involve the hepatic hilum and the confluence of the right and left hepatic ducts (Klatsken tumour);

• They may occur anywhere along the hepatic and common bile duct system.

• These cancers often present with symptoms and findings of bile duct obstruction.

• Predominant symptoms are pruritus, jaundice, and weight loss.

BLOOD TESTS

• Serum biochemical studies demonstrate a cholestatic profile (ie, elevation of alkaline phosphatase and bilirubin levels

• The serum CA 19-9 level is commonly

elevated but is nonspecific

IMMAGING • Ultrasonography and CT scan reveal bile duct

obstruction with dilation of proximal bile ducts, but a mass lesion is seldom identified.

• Cholangiography shows a stricture with proximal bile duct dilation.

• Specimens obtained by brush cytologic testing at the time of endoscopic or percutaneous cholangiography

• Histologic and cytologic confirmation of malignancy is challenging

Surgery

• Hilar cholangiocarcinoma accounts for two thirds of all cases of extrahepatic cholangiocarcinoma.

• Intrahepatic and distal extrahepatic

cholangiocarcinomas are less common.

• Surgical resection remains the mainstay of treatment, consisting of liver resection and pancreaticoduodenectomy, respectively.

Surgery

• Contrast-enhanced CT and cholangiography are necessary for appropriate patient selection and surgical planning.

• Current criteria for unresectability include the following: (1) bilateral ductal extension to secondary radicles, the main portal vein, hepatic artery, N2 lymph node metastases and distant metastases.

Surgery • The perioperative mortality of hepatic resection

for hilar cholangiocarcinoma remains between 5% and 10% in major centers.

• Currently, cholecystectomy, lobar or extended lobar hepatic and bile duct resection, regional lymphadenectomy, and Roux-en-Y hepaticojejunostomy are the treatments of choice for hilar cholangiocarcinoma.

• Hepatic resection has resulted in 5-year survival rates of 20% to 25%.

Liver Transplantation

• Liver transplantation with neoadjuvant therapy should be used in patients with hilar cholangiocarcinoma, with long-term patient survival in the range of 28% at 5.

• A variety of chemotherapy agents have been evaluated, but in general the response to these agents has been limited.

• Palliation throuh ERCP and stenting

PANCREATIC CANCER

Risk factors

• Smoking

• Advanced age

• Male sex - The male-to-female ratio of pancreatic cancer is 1.3:1.

• Chronic pancreatitis - Inflammation of the pancreas

• Diabetes mellitus

• Family history of pancreatic cancer

Presentation • The initial symptoms of pancreatic cancer are

often nonspecific and begin a few months before diagnosis.

• These symptoms include mild epigastric pain, back pain, and weight loss.

• The most common presentation of patients at diagnosis of pancreatic cancer is with obstructive jaundice accompanied by itching and pale stools

• Development of new-onset diabetes in elderly patients can herald pancreatic cancer.

Physicalexamination

• Signs of jaundice (skin and icterus).

• The gallbladder may be palpable (Courvoisier sign). This may be associated with underlying pancreatic malignancy.

• Look for signs of weight loss, adenopathies.

• Note the presence or absence of ascites.

• A high fever and chills suggest a coexisting cholangitis.

• Abdominal pain is usually associated with gall stone obstruction.

• Malignancy is more commonly associated with the absence of pain and tenderness during the physical examination.

• Excoriations suggest prolonged cholestasis or high-grade biliary obstruction.

Pathophysiology

• Typically, pancreatic cancer first metastasizes to regional lymph nodes, then to the liver and, less commonly, to the lungs.

• It can also directly invade surrounding visceral organs such as the duodenum, stomach, and colon, or it can metastasize to any surface in the abdominal cavity via peritoneal spread.

• Ascites may result, and this has an ominous prognosis.

Investigations

• laboratory studies to confirm cholestasis, measurement of levels of tumor marker CA 19-9.

• Approximately 75% of all pancreatic carcinomas occur within the head or neck of the pancreas

• 15-20% occur in the body of the pancreas, and 5-10% occur in the ta

Histology

• The most common type of pancreatic cancer arises from the exocrine glands and is called adenocarcinoma of the pancreas.

• The endocrine glands of the pancreas can give rise to a completely different type of cancer, referred to as pancreatic neuroendocrine carcinoma or islet cell tumor.

Surgery

• Surgical resection of localized pancreatic adenocarcinoma currently provides the only opportunity for cure.

• In high-volume centers, operative mortality is frequently reported to be less than 3%.

• Pancreaticoduodenectomy is the procedure of choice for lesions of the pancreatic head, whereas lesions of the body and tail require distal pancreatectomy.

Selecting appropriate patients• Selection for resection includes evaluation of

patient-related factors (comorbidities and functional status) and tumor-related factors.

• Criteria for tumor resectability typically include the following:

(1) absence of metastatic disease(2) patency of the portal vein and superior

mesenteric vein confluence(3) absence of celiac axis or superior mesenteric

artery involvement

Palliative treatment

• To address quality of life issues• Not aimed at curing the pathology • Includesa. pain managementb. pruiritus and jaundice by stentingc. Nutritional supportd. Address gastric outlet and duodenal

obstruction if present

Liver tumors

• Benign haemangioma, adenoma, focal nodular hyperplasia

• Malignant a. Primary Hepatocellular ca and

cholangiocarcinoma b. Metastatic (MOST COMMON)

HCC

• Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte, generally leading to death within 6-20 months.

• Hepatocellular carcinoma frequently arises in the setting of cirrhosis, appearing 20-30 years following the initial insult to the liver

• Fibrolamellar hepatocellular ca occurs in non cirrhotic liver

Cirrhosis • Cirrhosis is the major risk factor for HCC

• Cirrhosis arises in pts with chronic hepatitis B or C virus infection and alcohol use.

• Rare risk factors for cirrhosis are; hereditary hemochromatosis, α1-antitrypsin deficiency, autoimmune hepatitis, primary biliary cirrhosis.

• Fungal aflatoxins that contaminate grains and legumes

also have a synergistic effect with other causes of liver injury and contribute to the development of liver cancer in parts of sub-Saharan Africa and Asia

History

• Patients generally present with symptoms of advancing cirrhosis.

• Pruritus• Jaundice• Splenomegaly• Variceal bleeding• Cachexia• Increasing abdominal girth (portal vein occlusion by

thrombus with rapid development of ascites)• Hepatic encephalopathy• Right upper quadrant pain (uncommon)

Physical examination

• Jaundice• Ascites• Hepatomegaly• Alcoholic stigmata (gynaecomastia, spider

angiomata)• Flapping tremors• Pedal edema• Periumbilical collateral veins

Laboratory Studies

• Expect derranged liver functions consistent with cirrhosis. total bilirubin, aspartate aminotransferase (AST), alkaline phosphatase, albumin, and prothrombin time to show results

• Alpha-fetoprotein (AFP) is elevated in 75% of cases. The level of elevation correlates inversely with prognosis.

• In the setting of a growing mass, cirrhosis, and the absence of acute hepatitis, a level greater than 1000 ng/mL is considered diagnostic of hepatocellular carcinoma (without biopsy).

CT

Histologic Findings

• Histology is quite variable, ranging from well-differentiated tumors to anaplastic tumors.

• The fibrolamellar subtype is associated with a better prognosis, possibly because it is not associated with cirrhosis and is more likely to be resectable.).

Medical Care

• Available treatment options depend on the size, number, and location of tumors; presence or absence of cirrhosis

• Operative risk based on extent of cirrhosis and comorbid diseases; overall performance status; patency of portal vein; and presence of metastatic disease.

• Treat the complications of cirrhosis with diuretics,

paracentesis for ascites, lactulose for encephalopathy, ursodiol for pruritus, sclerosis or banding for variceal bleeding, and antibiotics for spontaneous bacterial peritonitis.

Surgical treatment• Surgical resection and liver transplantation are

the only chances of cure but have limited applicability.

• The main prognostic factors for resectability are tumor size and liver function.

• Only about 5% of hepatocellular carcinoma patients are suitable for transplantation; these patients may have a 5-year survival of greater than 75%.

• Other local therapies are chemoembolization, ethanol ablation, radiofrequency ablation, cryoablation, and radiotherapy.