Pancreatic Cancer

Pancreatic ductal adenocarcinoma is the 13th most commonly diagnosed cancer worldwide and the 8th most common cause of cancer death.  In the USA and the UK it is 4th and 5th, respectively, on the death list.  It afflicts men and women in almost equal numbers and is extremely difficult to diagnose in its early stages, for which reason over half of patients have distant metastases and more than one quarter have regional spread at the time of diagnosis.  The overall 5-year survival rate is less than 5%.

New cases/year

World 2008: 278,684 [male: 144,859, female: 133,825];

USA 2011 (est): 44,030; UK 2008: 8,085

Deaths/year

World 2008: 266,669 [male: 138,377, female: 128,292];

USA 2011 (est): 37,660; UK 2008: 7,781

Risk factors

Smoking is thought to contribute to ~20% of cases. Diabetes, long term inflammation of the pancreas (chronic pancreatitis, 70% of which is caused by heavy alcohol consumption) and stomach ulcers. Diets high in meats and fats, diets low in vegetables and folate. Possible hereditary factors in ~10%. Rare under the age of 40: 63% of new cases present over the age of 70.

Symptoms

Weight loss, stomach or back pain, jaundice (yellow skin color), development of diabetes.

Staging

TNM system is used (see Tumour staging). Patients almost always present with stage 4.

Classification

CA19-9 in the blood is used as a marker for colon and pancreatic cancer.  However it has low sensitivity and specificity, its level being elevated in some non-malignant diseases.  In patients not expressing Lewis antigen (~5% of cases) no increase in CA19-9 levels occurs even with large tumours.

Major gene mutations

80-95% of these tumours have mutations in KRAS, so they resemble leukemias in that one major mutation drives development. Other frequently mutated genes are P53, CDKN2 and PIK3CA.

Whole genome sequencing of tumour slices has shown that they are made up of mixtures of sub-clones. On average it takes 15 years for metastases to appear from these primary growths. From that point the average lifespan is two years.

Treatment

Because this cancer generally presents late and metastasises early it is usually resistant to treatment.  Fewer that 20% of cases are treatable by surgery. Gemcitabine gives partial response in 10% of cases and in 30-40% stabilizes the disease. Other inhibitors are under development.

Side effects

Gemcitabine has multiple side effects including allergy, nausea, hair loss. General suppression of the immune system and increased infection risk.

Prognosis

Poor: mean overall survival time is 6-7 months. The survival rates for stages of exocrine pancreatic cancer range from 37% (Stage IA) to 1% (Stage IV).

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