Pancreatic Cancer

Pancreatic Cancer

Background: In the United States, approximately 30,000 people die of pancreatic cancer each year. Among cancers of the gastrointestinal tract, it is the third most common malignancy and the fifth leading cause of cancer-related death.

Pancreatic Cancer • Background: • The disease is difficult to diagnose in its early stages, and most patients have incurable disease by the time they present with symptoms. • The overall 5-year survival rate for this disease is less than 5%.

Pancreatic Cancer • Pathophysiology: • Pancreatic cancers can arise from both the exocrine and endocrine portions of the pancreas. • Of pancreatic tumors, 95% develop from the exocrine portion of the pancreas.

Pancreatic Cancer

• Pathophysiology: • 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 tail.

Pancreatic Cancer

• Pathophysiology: • Typically, pancreatic cancer first metastasizes to regional lymph nodes, then to the liver • It can also directly invade surrounding visceral organs such as the: • ► duodenum • ► stomach, and colon. •

• ► and less commonly, to the lungs.

Pancreatic Cancer • Pathophysiology: • The molecular genetics of pancreatic adenocarcinoma have been well studied. • ► Of these tumors, 80-95% have mutations in the KRAS2 gene. • ► and 85-98% have mutations, or deletions, in the CDKN2 gene.

Pancreatic Cancer • Pathophysiology: • 50% have mutations in TP53. • • and about 55% have deletions or mutations of Smad4.

Pancreatic Cancer • Pathophysiology: • Remember • Although studies are underway, the genetic mutations associated with pancreatic adenocarcinoma are not yet clinically useful in screening for or diagnosing the disease.

Pancreatic Cancer • Pathophysiology: • As in other organs, chronic inflammation is a predisposing factor in the development of pancreatic cancer. • Patients with chronic pancreatitis from alcohol, especially those with familial forms, have much higher incidence and an earlier age of onset of pancreatic carcinoma.

Pancreatic Cancer

• Frequency: • Worldwide, pancreatic cancer ranks thirteenth in incidence but eighth as a cause of cancer death.

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Pancreatic Cancer

• Frequency: • Most other countries have incidence rates of 8-12 cases per 100,000 persons per year.

• ► For example, the incidence in India is less than 2 cases per 100,000 persons per year.

Pancreatic Cancer • Mortality/Morbidity: • Pancreatic carcinoma is unfortunately usually a fatal disease. • Patients eventually succumb to the consequence of : • ► Local lymph node metastasis • ► Distant metastasis

Pancreatic Cancer • Mortality/Morbidity: • Remember • ► Overall survival is less than 5%. • ► Patients able to undergo surgery 20% of cases.

• ►After surgery: • Survival time is 12-19 months • 5 years survival rate 15- 20%

Pancreatic Cancer • Mortality/Morbidity: • The best predictors of long-term survival after surgery are: •

1) a tumor diameter of less than 3 cm

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2) no nodal involvement

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3) and negative resection margins.

Pancreatic Cancer

• Sex: • The male-to-female ratio for pancreatic cancer is 1.21.5:1.

• Age: • The median age at diagnosis is 69 years in whites and 65 years in blacks.

Pancreatic Cancer

• Clinical Presentation • History • The early clinical diagnosis of pancreatic cancer is fraught with difficulty. • Unfortunately, the initial symptoms are often quite nonspecific and subtle in onset.

Pancreatic Cancer • Clinical Presentation • History • Patients typically report the gradual onset of nonspecific symptoms such as: • • • • •

Anorexia malaise nausea fatigue and midepigastric or back pain.

Pancreatic Cancer

• Clinical Presentation • History • Significant weight loss is a characteristic feature of pancreatic cancer.

Pancreatic Cancer

• Clinical Presentation • History • These initial symptoms can be easily attributed to other processes unless a physician has a high index of suspicion for the possibility of underlying pancreatic carcinoma.

Pancreatic Cancer • Clinical Presentation • History • ► Delayed diagnosis is a common problem in patients with pancreatic cancer.

• ► With fewer than a third of patients being diagnosed within 2 months of the onset of their symptoms.

Pancreatic Cancer • Clinical Presentation • History • Pain is the most common presenting symptom in patients with pancreatic cancer.

• Typically, it is midepigastric in location, with radiation of the pain sometimes occurring to the mid - or lowerback region.

Pancreatic Cancer • Clinical Presentation • History • Back radiation of the pain is a worrisome sign indicating retroperitoneal invasion of the splanchnic nerve plexus by the tumor.

Pancreatic Cancer • Clinical Presentation • History • Weight loss may be related to: • ► anorexia • ► malabsorption from pancreatic exocrine insufficiency caused by pancreatic duct obstruction by the cancer.

Pancreatic Cancer • Clinical Presentation • History • The onset of diabetes mellitus within the previous year is sometimes associated with pancreatic carcinoma.

Pancreatic Cancer • Clinical Presentation • History

• ► The most characteristic sign of pancreatic carcinoma of the head of the pancreas is painless obstructive jaundice.

Pancreatic Cancer • Clinical Presentation • History • a) Patients with this sign may come to medical attention before their tumor grows large enough to cause abdominal pain. • b) These patients usually notice a darkening of their urine and lightening of their stools before they or their families notice the change in skin pigmentation. • c) Pruritus may accompany obstructive jaundice.

Pancreatic Cancer • Clinical Presentation • History • Migratory thrombophlebitis (i.e. Trousseau sign) and venous thrombosis also occur with higher frequency in patients with pancreatic cancer.

Pancreatic Cancer • Clinical Presentation • Physical • The physical examination findings in a patient with pancreatic cancer are usually limited to evidence of: • ► significant weight loss • • ► and some mild-to-moderate midepigastric tenderness.

Pancreatic Cancer • Clinical Presentation • Physical • Patients with jaundice may have a palpable gallbladder (i.e. Courvoisier sign).

• ► and may have evidence of skin excoriations from pruritus.

Pancreatic Cancer • Clinical Presentation • Physical • Patients presenting with end-stage disease may have: • ■ ascites • ■ a palpable abdominal mass hepatomegaly from liver metastases • ■ or splenomegaly from portal vein obstruction.

Pancreatic Cancer • Causes: • Smoking – Smoking is the most common environmental risk factor for pancreatic carcinoma. – People who smoke have at least a 2-fold increased risk for pancreatic cancer.

• Causes: • Dietary factors Alcohol consumption does not appear to be an independent risk factor for pancreatic cancer unless it is associated with chronic pancreatitis.

Causes ► The incidence of pancreatic cancer appears to be higher in people with increased energy. ► and lower in those with a diet rich in fresh fruits and vegetables.

Pancreatic Cancer Causes • Diabetes mellitus ► Patients with diabetes mellitus of at least 5years' duration have a 2-fold increased risk of developing pancreatic carcinoma.

Pancreatic Cancer • Causes

• ► Chronic pancreatitis. • ► Genetic factors

Pancreatic Cancer • Differential Diagnosis • Choledocholithiasis Cholelithiasis Duodenal Ulcers Gastric Cancer Gastric Ulcers Neoplasms of the Endocrine Pancreas Pancreatitis, Acute Pancreatitis, Chronic

Pancreatic Cancer • Differential Diagnosis • Abdominal Aortic Aneurysm Ampullary Carcinoma Bile Duct Strictures Bile Duct Tumors Cholangitis Cholecystitis Choledochal Cysts

• Workup • Lab studies • ► General laboratory studies

The laboratory findings in patients with pancreatic cancer are usually nonspecific. ► As with many chronic diseases, a mild anemia may be present.

►Thrombocytosis is also sometimes observed in patients with cancer.

• Workup • Lab studies • ►General laboratory studies • Patients presenting with obstructive jaundice show significant elevations in: • bilirubin (conjugated and total) • alkaline phosphatase (ALP) • gamma-glutamyl transpeptidase (GGT) • and • aspartate aminotransferase (ASP) and alanine aminotransferase (ALT).

• Workup • Lab studies • ►General laboratory studies • Interestingly, amylase and lipase are infrequently elevated in pancreatic carcinoma.

• Workup • Lab studies • ►General laboratory studies

Patients may also have laboratory evidence of malnutrition e.g. low serum albumin or cholesterol levels.

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Workup Lab studies ►General laboratory studies Tumor markers – The major useful tumor marker for pancreatic carcinoma is carbohydrate antigen 19-9 (CA 19-9).

• Workup • Imaging Studies • computed tomography (CT) scanning. ultrasonography (US). • magnetic resonance imaging (MRI). • (ERCP). • and positron emission tomography (PET). Scanning

• TREATMENT

• Medical Care: • Chemotherapy • Palliative therapy

• Surgical Care: • Pancreaticoduodenectomy (Whipple operation). • Neoadjuvant chemoradiation.

• Thanks