Pancreatic cancer

Pancreatic cancer is a disease that starts when cells in the pancreas, a gland behind the stomach, grow out of control and form a mass. These cancerous cells can spread to other parts of the body. The most common type, called pancreatic adenocarcinoma, makes up about 90% of cases and begins in the part of the pancreas that creates digestive enzymes.

Some signs of this cancer may include yellow skin, abdominal or back pain, unexplained weight loss, and changes in the color of stools or urine. Often, there are no early signs, and by the time these symptoms appear, the cancer may have already spread.

Pancreatic cancer is rare before the age of 40 and mostly affects older adults, with more than half of cases occurring in people over 70. There are different types of pancreatic cancer, most of which begin in the part of the pancreas that produces digestive enzymes. Another smaller group starts in the part that makes hormones, called pancreatic neuroendocrine tumors. Both types are more common in men, but some rare forms affect women or children.

Signs and symptoms

Pancreatic cancer often doesn’t show clear signs at first, so it’s usually found only after it has spread. This makes it hard to treat early. However, some types of pancreatic tumors can cause symptoms because they make too much of certain hormones.

Common signs of pancreatic cancer include:

• Pain in the upper belly or back, which might get worse at night and stay for a long time. This pain can help doctors know where in the pancreas the tumor might be.
• Yellowing of the skin or eyes, called jaundice, which happens when a tumor blocks a tube that helps digest food.
• Unexplained weight loss, either because of loss of appetite or trouble digesting food.
• Feeling full quickly, nausea, and changes in stool that might smell bad or be hard to flush.
• Diabetes that appears suddenly, especially in people over 50, can sometimes be an early warning sign of pancreatic cancer.

Other findings

• Blood clots can sometimes form in people with pancreatic cancer, affecting veins in the body.
• Feeling down or depressed has also been linked to pancreatic cancer in some cases.

Pancreatic cancer metastasis

When pancreatic cancer spreads, it often reaches nearby lymph nodes first, then the liver, belly area, large intestine, or lungs. It can also spread to bones or the brain, but this is rare. Sometimes, cancers from other parts of the body, like the kidney or colon, can spread to the pancreas. Surgery may help treat these cases.

Risk factors

Risk factors for pancreatic cancer include:

• Age, sex, and ethnicity – The chance of getting pancreatic cancer goes up as people get older. Most cases happen after age 65, and cases before age 40 are rare. The disease is a bit more common in men than in women. In the United States, it happens more often in African Americans, although it is less common in Africa.
• Cigarette smoking – Smoking is a major risk factor for pancreatic cancer. The more cigarettes someone smokes and the longer they smoke, the higher the risk. Even after quitting, the risk stays higher for about 20 years before it goes down.
• Obesity – Having a very high body mass index can increase the risk of pancreatic cancer by about half.
• Family history – Some families have a higher chance of getting pancreatic cancer. If a close family member has had the disease, especially if they were young when it happened, the risk goes up. Some rare genetic conditions also increase the risk.

Other factors that may increase risk include certain rare genetic conditions, long-term diabetes mellitus, and having chronic pancreatitis. While alcohol abuse can lead to chronic pancreatitis, it has not been proven to directly cause pancreatic cancer on its own.

Pathophysiology

Pancreatic cancer starts when cells in the pancreas grow out of control and form a lump. These cancer cells can spread to other parts of the body.

There are several types of changes in the pancreas that can lead to cancer. One type is called pancreatic intraepithelial neoplasia (PanIN). These tiny changes are often found in people who never had cancer. Another type is called intraductal papillary mucinous neoplasm (IPMN). These are bigger changes that can sometimes turn into cancer. A third type is pancreatic mucinous cystic neoplasm (MCN), which mostly affects women. There is also a type called intraductal tubulopapillary neoplasm, which is less common.

When pancreatic cancer spreads, it can change the way the body’s immune system works, making it harder for the body to fight the cancer.

Diagnosis

Pancreatic cancer often doesn't show clear signs at first, making it hard to notice early. Symptoms can vary depending on where the cancer is in the pancreas. Common signs include unexpected weight loss, feeling weak, or having nausea. Some people might also feel pain or notice changes in their urine or stool color.

Doctors use special imaging tests, like CT scans and ultrasound, to look for signs of cancer and see if it can be removed through surgery. These tests help doctors understand more about the cancer and plan the best treatment.

Histopathology

The most common type of pancreatic cancer has certain features when looked at under a microscope. These features make it challenging to treat because they create an environment that limits the reach of some medicines.

Genetic profile of PDAC

Most cases of a common type of pancreatic cancer have changes in specific genes. These changes affect how cells grow and repair their DNA, making the cancer harder to treat. Knowing about these gene changes can help doctors predict how the cancer might behave and choose treatments that could work better.

Staging

Exocrine cancers

Pancreatic cancer is grouped into stages to describe how far it has spread. Doctors use imaging tests to determine the stage, which helps decide on the best treatment. Early-stage cancers that haven’t spread far might be removed through surgery. Later stages may involve cancer that has spread to nearby organs or farther parts of the body.

PanNETs

There is another way to group certain types of pancreatic tumors based on how the cells look and act. This helps doctors understand how the tumor might grow and choose the right treatment.

Prevention and screening

The American Cancer Society suggests not smoking, keeping a healthy weight, and eating more fruits, vegetables, and whole grains. They also recommend eating less red and processed meat. While these steps may help, there is no strong proof they will stop pancreatic cancer.

For most people, testing large groups for pancreatic cancer is not helpful and might cause harm. However, for people with a high risk due to family history, doctors may suggest special tests like endoscopic ultrasound or MRI/CT imaging. Some studies also suggest that taking aspirin could lower the chance of getting pancreatic cancer, but more research is needed.

Management

Exocrine cancer

After diagnosing cancer, doctors first check if the tumor can be removed by surgery, which is the only cure. This depends on how much the cancer has spread and its location. The patient's overall health is also considered, though age alone isn't a barrier to surgery.

Chemo and radiation treatments are often used, whether or not surgery is possible. These treatments are usually managed by a team of cancer specialists in larger medical centers.

Surgery

Surgery to cure the cancer is possible in only about 20% of new cases. Even when it seems possible, it might not be until during the operation. Factors include how close the tumor is to important blood vessels and the patient's ability to handle major surgery.

For cancers in the front part of the pancreas, a major operation called the Whipple procedure is used. It involves removing part of the pancreas and reconnecting the digestive system. Another operation, called distal pancreatectomy, is used for cancers in the back part of the pancreas and often includes removing the spleen. These surgeries are complex and can have complications.

Even when surgery seems successful, tiny cancer cells might remain, and special tests are done to check. Sometimes a small camera-guided surgery is done to better understand the outcome of a full operation.

After surgery, chemo treatments are often used to help prevent the cancer from returning. For patients who cannot have surgery, chemo can help extend life or improve quality of life. Some treatments are used before surgery to shrink the tumor, but this can delay surgery.

Chemotherapy

Chemo treatments like gemcitabine or a combination of drugs are used after surgery if the patient is healthy enough. For those who cannot have surgery, chemo can help manage the disease. New treatments are being tested in clinical trials.

Radiotherapy

Radiation treatment after surgery has been debated for years. Some studies suggest it may not be needed, while others continue to test its use. Radiation can also be used to shrink tumors that cannot be removed by surgery, but results vary.

Targeted therapy

Immunotherapy

Personalized mRNA vaccines

A 2025 study showed promising results for personalized vaccines made from a patient's own tumor genetic material. These vaccines helped the immune system recognize cancer cells in some patients, when used along with standard treatments.

PanNETs

Main articles: Neuroendocrine tumor and Pancreatic neuroendocrine tumor

Treatment for PanNETs depends on the tumor's size and location. Small tumors may be monitored over time. Larger tumors can sometimes be removed by surgery. Medications can help control hormone levels or slow tumor growth. Other treatments like targeted therapy or radiation may be used if needed.

Palliative care

Palliative care helps manage symptoms and improve quality of life for people with serious illnesses like pancreatic cancer. It focuses on treating pain, nausea, and other symptoms rather than curing the disease. Treatments can include medications, procedures to block pain signals, or inserting tubes to help with digestion. Palliative care also supports patients and families in making difficult decisions.

Prognosis

Pancreatic cancer often has a poor outlook because it is usually found late, when it has already grown or spread. However, for some less common types of pancreatic tumors called PanNETs, many do not cause symptoms and may even be harmless. Even when these cannot be treated with surgery, about 16% of people live for five more years.

For most cases of the common type of pancreatic cancer, treatments can help people live longer, but usually not more than one year. In the United States, the chance of living five years after being diagnosed has slowly increased over time. For a smaller group of early-stage cases, about 20% of people in America live for five years after diagnosis.

Many genes affect how this type of cancer progresses, with some linked to worse outcomes and others to better ones.

Epidemiology

Pancreatic cancer is a serious disease that happens when cells in the pancreas grow out of control. In 2015, it caused over 400,000 deaths around the world. Even though it isn’t one of the most common cancers, it is one of the leading causes of cancer deaths.

This type of cancer is found more often in developed countries. In the United States, about 1 in 67 people may develop it during their lifetime. It happens a bit more often in men than women, but the difference has become smaller in recent years. Some groups, like African Americans in the U.S., have higher risks than others.

PanNETs

A less common type of pancreatic cancer is called pancreatic neuroendocrine tumors (PanNETs). These tumors are rare, occurring in about 5 cases per one million people each year. Many of these tumors do not cause symptoms and might not even be noticed unless found during tests for other reasons. They make up only about 1 to 2% of all pancreatic tumors.

History

Recognition and diagnosis

In the 1700s, an Italian scientist named Giovanni Battista Morgagni was the first to describe cases of cancer in the pancreas. For many years, doctors were unsure if this disease really existed because it looked similar to another condition called pancreatitis. More detailed reports started to appear in the 1800s. By the early 1900s, cancer of the pancreas was widely accepted as a real illness.

Doctors also began to learn about a special type of pancreatic tumor in the 1900s. In 1927, they reported the first case of a tumor that caused too much insulin. Later, two American doctors identified another type of tumor linked to severe stomach ulcers. Today, these tumors are called neuroendocrine tumors.

Modern imaging tools now help doctors find early signs of pancreatic cancer more often.

Surgery

The first operation to remove part of the pancreas and intestine was performed in 1898, but the patient did not survive long. Early surgeries were difficult because doctors thought removing certain parts would be too dangerous. It wasn’t until 1935 that a successful operation was reported in the United States. This operation, now known as the Whipple procedure, remained very risky for many years.

Over time, new discoveries, like the use of vitamin K to prevent dangerous bleeding and the development of safe blood transfusion methods, helped patients survive surgery better. By the 1970s, about 25% of patients still did not survive the operation. However, as hospitals became more experienced, survival rates improved greatly. Today, the Whipple procedure is much safer, with very low rates of death during or shortly after surgery.

Research directions

Scientists are studying many ways to better understand and treat pancreatic cancer. They look at how genes work, ways to find the disease early, and different treatments for people at various stages of the illness. They are also testing new surgery methods and treatments that target specific parts of the cancer cells.

Researchers are also interested in how diabetes might be linked to pancreatic cancer and whether finding diabetes early could help diagnose cancer sooner. They are trying new drugs that target how cancer cells grow and spread, and they are studying ways to use the body’s own immune system to fight cancer. New techniques and tools are being tested to improve treatment and help people live longer.