PENCREATIC CANCER : SYMPTOMS, CAUSES, PREVENTION AND TREATMENT

Pancreatic cancer occurs when cells in your pancreas develop mutations in their DNA. These mutations cause cells to grow uncontrollably and to continue living after normal cells would die. These accumulating cells can form a tumor. Untreated pancreatic cancer spreads to nearby organs and blood vessels.

Most pancreatic cancer begins in the cells that line the ducts of the pancreas. This type of cancer is called pancreatic adenocarcinoma or pancreatic exocrine cancer. Rarely, cancer can form in the hormone-producing cells or the neuroendocrine cells of the pancreas. These types of cancer are called islet cell tumors, pancreatic endocrine cancer and pancreatic neuroendocrine tumors.

More than 56,000 Americans are expected to be diagnosed with pancreatic cancer in 2019. That is more than 150 people diagnosed every day.
Pancreatic cancer is the ninth most commonly diagnosed cancer in women and the 10th most commonly diagnosed in men in the U.S.
Signs and Symptoms of Pancreatic Cancer

The symptoms of exocrine pancreatic cancers and pancreatic neuroendocrine tumors (NETs) are often different, so they are described separately.

Having one or more of the symptoms below does not mean you have pancreatic cancer. In fact, many of these symptoms are more likely to be caused by other conditions. Still, if you have any of these symptoms, it’s important to have them checked by a doctor so that the cause can be found and treated, if needed.

Signs and symptoms of exocrine pancreatic cancer

Early pancreatic cancers often do not cause any signs or symptoms. By the time they do cause symptoms, they have often already spread outside the pancreas.

Jaundice and related symptoms

Jaundice is yellowing of the eyes and skin. Most people with pancreatic cancer (and nearly all people with ampullary cancer) will have jaundice as one of their first symptoms.

Jaundice is caused by the buildup of bilirubin, a dark yellow-brown substance made in the liver. Normally, the liver excretes bilirubin as part of a liquid called bile. Bile goes through the common bile duct into the intestines, where it helps break down fats. It eventually leaves the body in the stool. When the common bile duct becomes blocked, bile can’t reach the intestines, and the level of bilirubin in the body builds up.

Cancers that start in the head of the pancreas are near the common bile duct. These cancers can press on the duct and cause jaundice while they are still fairly small, which can sometimes lead to these tumors being found at an early stage. But cancers that start in the body or tail of the pancreas don’t press on the duct until they have spread through the pancreas. By this time, the cancer has often spread beyond the pancreas as well.

When pancreatic cancer spreads, it often goes to the liver. This can also lead to jaundice.

Dark urine: Sometimes, the first sign of jaundice is darker urine. As bilirubin levels in the blood increase, the urine becomes brown in color.

Light-colored or greasy stools: Bilirubin normally helps give stools their brown color. If the bile duct is blocked, stools might be pale or gray. Also, if bile and pancreatic enzymes can’t get through to the intestines to help break down fats, the stools can become greasy and might float in the toilet.

Itchy skin: When bilirubin builds up in the skin, it can start to itch as well as turning yellow.

Pancreatic cancer is not the most common cause of jaundice. Other causes, such as gallstones, hepatitis, and other liver and bile duct diseases, are much more common.

Belly or back pain

Pain in the abdomen (belly) or back is common in pancreatic cancer. Cancers that start in the body or tail of the pancreas can grow fairly large and start to press on other nearby organs, causing pain. The cancer may also spread to the nerves surrounding the pancreas, which often causes back pain. Of course, pain in the abdomen or back is fairly common and is most often caused by something other than pancreatic cancer.

Weight loss and poor appetite

Unintended weight loss is very common in people with pancreatic cancer. These people often have little or no appetite.

Nausea and vomiting

If the cancer presses on the far end of the stomach it can partly block it, making it hard for food to get through. This can cause nausea, vomiting, and pain that tend to be worse after eating.

Gallbladder or liver enlargement

If the cancer blocks the bile duct, bile can build up in the gallbladder, making it larger. Sometimes a doctor can feel this (as a large lump under the right side of the ribcage) during a physical exam. It can also be seen on imaging tests.

Pancreatic cancer can also sometimes enlarge the liver, especially if the cancer has spread to the liver. The doctor might be able to feel this below the right ribcage as well on an exam, or it might be seen on imaging tests.

Blood clots

Sometimes, the first clue that someone has pancreatic cancer is a blood clot in a large vein, often in the leg. This is called a deep vein thrombosis or DVT. Symptoms can include pain, swelling, redness, and warmth in the affected leg. Sometimes a piece of the clot can break off and travel to the lungs, which might make it hard to breathe or cause chest pain. A blood clot in the lungs is called a pulmonary embolism or PE.

Still, having a blood clot does not usually mean that you have cancer. Most blood clots are caused by other things.

Fatty tissue abnormalities

Some people with pancreatic cancer develop an uneven texture of the fatty tissue underneath the skin. This is caused by the release of the pancreatic enzymes that digest fat.

Diabetes

Rarely, pancreatic cancers cause diabetes (high blood sugar) because they destroy the insulin-making cells. Symptoms can include feeling thirsty and hungry, and having to urinate often. More often, cancer can lead to small changes in blood sugar levels that don’t cause symptoms of diabetes but can still be detected with blood tests.

Signs and symptoms of pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (NETs) often release excess hormones into the bloodstream. Different types of tumors make different hormones, which can lead to different symptoms.

Gastrinomas

These tumors make gastrin, a hormone that tells the stomach to make more acid. Too much gastrin causes a condition known as Zollinger-Ellison syndrome, in which the stomach makes too much acid. This leads to stomach ulcers, which can cause pain, nausea, and loss of appetite. Severe ulcers can start bleeding. If the bleeding is mild, it can lead to anemia (too few red blood cells), which can cause symptoms like feeling tired and being short of breath. If the bleeding is more severe, it can make stool black and tarry. Severe bleeding can itself be life-threatening.

If the stomach acid reaches the small intestine, it can damage the cells of the intestinal lining and break down digestive enzymes before they have a chance to digest food. This can cause diarrhea and weight loss.

Glucagonomas

These tumors make glucagon, a hormone that increases glucose (sugar) levels in the blood. Most of the symptoms that can be caused by a glucagonoma are mild and are more often caused by something else.

Excess glucagon can raise blood sugar, sometimes leading to diabetes. This can cause symptoms such as feeling thirsty and hungry, and having to urinate often.

People with these tumors can also have problems with diarrhea, weight loss, and malnutrition. The nutrition problems can lead to symptoms like irritation of the tongue and the corners of the mouth.

The symptom that brings most people with glucagonomas to their doctor is a rash called necrolytic migratory erythema. This is a red rash with swelling and blisters that often travels from place to place on the skin.

Insulinomas

These tumors make insulin, which lowers blood glucose levels. Too much insulin leads to low blood sugar, which can cause symptoms like weakness, confusion, sweating, and rapid heartbeat. When blood sugar gets very low, it can lead to a person passing out or even going into a coma and having seizures.

Somatostatinomas

These tumors make somatostatin, which helps regulate other hormones. Symptoms of this type of tumor can include belly pain, nausea, poor appetite, weight loss, diarrhea, symptoms of diabetes (feeling thirsty and hungry, and having to urinate often), and jaundice (yellowing of the skin and eyes).

The early symptoms of a somatostatinoma tend to be mild and are more often caused by other things, so these tumors tend to be diagnosed at an advanced stage. Often, they are not found until they spread to the liver, when they cause problems like jaundice and pain.

VIPomas

These tumors make a substance called vasoactive intestinal peptide (VIP). Too much VIP can lead to problems with diarrhea. This may be mild at first, but gets worse over time. By the time they are diagnosed, most people have severe, watery diarrhea.

Other symptoms can include nausea, vomiting, muscle cramps, feeling weak or tired, and flushing (redness and warmth in the face or neck).

People with these tumors also tend to have low levels of acid in their stomachs, which can lead to problems digesting food.

PPomas

These tumors make pancreatic polypeptide (PP), which helps regulate both the exocrine and endocrine pancreas. They can cause problems such as belly pain and an enlarged liver. Some people also get watery diarrhea.

Carcinoid tumors

These tumors often make serotonin or its precursor, 5-HTP. When a pancreatic tumor makes these substances, they first travel to the liver. The liver breaks these substances down before they can reach the rest of the body and cause problems. Because of this, carcinoid tumors often don’t cause symptoms until they spread outside the pancreas.

When these tumors do spread, it is most often to the liver. There, the cancer cells can release hormones directly into the blood leaving the liver. This can cause the carcinoid syndrome, with symptoms including flushing (redness and warmth in the face or neck), diarrhea, wheezing, and a rapid heart rate. These symptoms often occur in episodes, between which the person may feel fine.

Over a long time, the hormone-like substances released by these tumors can damage heart valves, causing shortness of breath, weakness, and a heart murmur (an abnormal heart sound).

Non-functioning neuroendocrine tumors

These tumors don’t make excess hormones, so they don’t cause symptoms in early stages and often grow quite large before they are found. Most of these are cancers and start to cause problems as they get larger or spread outside the pancreas. Symptoms can be like those from exocrine pancreas cancers, including jaundice (yellowing of the eyes and skin), belly pain, and weight loss.

Symptoms caused by the cancer spreading

When pancreatic NETs spread, most often they go to the liver. This can enlarge the liver, which can cause pain and loss of appetite. It can also affect liver function, sometimes leading to jaundice (yellowing of the skin and eyes) and abnormal blood tests.

These cancers can also spread to other organs and tissues. The symptoms depend on where the cancer is growing. For example, cancer spread to the lungs can cause shortness of breath or a cough. Spread to bones can cause pain in those bones.
Risk factors

Factors that may increase your risk of pancreatic cancer include:

• Chronic inflammation of the pancreas (pancreatitis)
• Diabetes
• Family history of genetic syndromes that can increase cancer risk, including a BRCA2 gene mutation, Lynch syndrome and familial atypical mole-malignant melanoma (FAMMM) syndrome
• Family history of pancreatic cancer
• Smoking
• Obesity
• Older age, as most people are diagnosed after age 65
• A large study demonstrated that the combination of smoking, long-standing diabetes and a poor diet increases the risk of pancreatic cancer beyond the risk of any one of these factors alone.

Prevention

You may reduce your risk of pancreatic cancer if you:

• Stop smoking. If you smoke, try to stop. Talk to your doctor about strategies to help you stop, including support groups, medications and nicotine replacement therapy. If you don't smoke, don't start.
• Maintain a healthy weight. If you are at a healthy weight, work to maintain it. If you need to lose weight, aim for a slow, steady weight loss — 1 to 2 pounds (0.5 to 1 kilogram) a week. Combine daily exercise with a diet rich in vegetables, fruit and whole grains with smaller portions to help you lose weight.
• Choose a healthy diet. A diet full of colorful fruits and vegetables and whole grains may help reduce your risk of cancer.

Consider meeting with a genetic counselor if you have a family history of pancreatic cancer. He or she can review your family health history with you and determine whether you might benefit from a genetic test to understand your risk of pancreatic cancer or other cancers.

Stages of Pancreatic Cancer

Stage is a term used in cancer treatment to describe the extent of the cancer's spread. The stages of pancreatic cancer are used to guide treatment and to classify patients for clinical trials. The stages of pancreatic cancer are:

• Stage 0: No spread. Pancreatic cancer is limited to top layers of cells in the ducts of the pancreas. The pancreatic cancer is not visible on imaging tests or even to the naked eye.
• Stage I: Local growth. Pancreatic cancer is limited to the pancreas, but has grown to less than 2 centimeters across (stage IA) or greater than 2 but no more than 4 centimeters (stage IB).
• Stage II: Local spread. Pancreatic cancer is over 4 centimeters and is either limited to the pancreas or there is local spread where the cancer has grown outside of the pancreas, or has spread to nearby lymph nodes. It has not spread to distant sites.
• Stage III: Wider spread. The tumor may have expanded into nearby major blood vessels or nerves, but has not metastasized to distant sites.
• Stage IV: Confirmed spread. Pancreatic cancer has spread to distant organs.

Treatments

The prognosis (chance of recovery) and treatment options depend on the following:

Whether or not the tumor can be removed by surgery.
The stage of the cancer (the size of the tumor and whether the cancer has spread outside the pancreas to nearby tissues or lymph nodes or to other places in the body).
The patient’s general health.
Whether the cancer has just been diagnosed or has recurred (come back).
Pancreatic cancer can be controlled only if it is found before it has spread, when it can be completely removed by surgery. If the cancer has spread, palliative treatment can improve the patient's quality of life by controlling the symptoms and complications of this disease.