Pancreatic cancer is a disease caused by the uncontrolled growth of cells in the pancreas. The pancreas is a hand-sized, pear-shaped organ located behind the stomach in the abdomen. It produces enzymes that help in digestion and hormones, such as insulin, which regulate blood glucose levels. Pancreatic cancers are often divided into 2 main types based on their site of origin in the pancreas:

1. Exocrine tumors: A majority of pancreatic cancers originate from the exocrine component. The exocrine component of the pancreas secretes enzymes that help in digestion and it consists of ducts and small sacs, called acini, at the end of the ducts. The majority of exocrine tumors arise from the internal lining of the ducts of the pancreas and are called ductal adenocarcinomas.

2. Endocrine tumors: The tumors originating from endocrine glands are called pancreatic neuroendocrine tumors (PNETs) or islet cell tumors. The endocrine component of the pancreas is tasked with synthesizing hormones. The tumors in this part may be functional meaning that they also synthesize hormones.

Pancreatic cancer begins when abnormal cells in the pancreas grow and divide out of control and form a tumor.

Symptoms

The symptoms of pancreatic cancer are not noticeable until the disease has progressed to an advanced stage. The silent nature of the disease coupled with its rapid spread makes it challenging to diagnose and manage pancreatic cancer which is reflected in its extremely low survival rates. Moreover, the symptoms are not uniform in all cases and they closely resemble those of pancreatitis – inflammation of the pancreas.

Following are some common symptoms of pancreatic cancer:

• Yellowing of the skin and eyes (jaundice)

• Abdominal pain that radiates to the back and arms

• Pale-colored stool

• Dark-colored urine

• Painful swelling of an arm or leg due to a blood clot

• Fatigue and weakness

• Unexplained weight loss

• Loss of appetite

• Nausea and vomiting

Diagnosis

The diagnosis of pancreatic cancer starts with a physical examination during which the signs of pancreatic cancer are evaluated in a patient presenting with one or more of the above symptoms. The clinician looks for signs of jaundice as well as any detectable structural abnormalities caused by the tumor by palpating the abdomen of the patient. Physical examination helps determine the course of further diagnostic workup which is also influenced by the patients’ age, overall general health status, and availability of various tests.

The diagnostic tests fall into the following 3 general domains:

1. Blood tests: Following physical examination, blood tests for bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, and amylase and/or lipase are performed.  Abnormal levels of these substances indicate the presence of pancreatic cancer; however, they may be altered in some other cancerous and non-cancerous conditions so they cannot pinpoint the presence of pancreatic cancer. In the context of blood tests suggestive of pancreatic cancer, the level of a tumor marker, called carbohydrate antigen 19-9 (CA 19-9), is evaluated. CA19-9 value greater than 100 U/mL indicates pancreatic cancer.

2. Imaging techniques: To locate the position of the tumor in the body and evaluate its progression, various types of imaging techniques are utilized. These tests include computed tomography (CT), positron emission tomography (PET), endoscopic retrograde cholangiopancreatography (ERCP), ultrasound, percutaneous transhepatic cholangiography (PTC), and magnetic resonance imaging (MRI).

   
   

3. Biopsy: A biopsy serves as a confirmatory test in which a small sample of tumor tissue is removed and analyzed under a microscope. It also facilitates the identification of specific mutated genes which serves as a crucial foundation for personalized treatment, allowing for targeted approaches based on individual genetic profiles. Two commonly used techniques are fine needle aspiration and core needle biopsy.

Management

Surgical resection of the tumor is the primary treatment option when the disease has not spread to other parts of the body. The extent of surgery depends on the size and location of the tumor, and accordingly whole or a part of the pancreas is removed. Depending upon the local spread of the disease, the nearby anatomical parts are also removed along with the pancreas.

After surgery, radiation therapy is used to kill the remaining cancer cells. The source of radiation can be placed outside the body, as in conventional radiotherapy, or inside the body. Moreover, newer types of radiotherapy offer more precise beams that only target the tumor thus avoiding the unwanted effects of radiation exposure.

Besides surgical resection and radiotherapy, chemotherapy is also included in the standard of care management of pancreatic cancer. Among the various chemotherapy drugs given, capecitabine, fluorouracil (5-FU) and gemcitabine are the most common. Chemotherapy can also be given before surgery.

The standard of care management for pancreatic cancer is not effective and it continues to have a high mortality rate that has not improved in decades. New therapeutic options such as targeted therapy and immunotherapy are being introduced to improve clinical outcomes. Further research is needed to diagnose pancreatic cancer when it has not spread to the other parts of the body and effectively manage it.