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 Pancreatic Cancer
In 2012, it's estimated almost 44,000 people in the U.S. will be diagnosed with pancreatic cancer. About one in 76 people in the U.S. will develop the disease. Pancreatic cancer affects equal numbers of men and women, almost always after the age of 45.

Cancer of the pancreas barely makes the top 10 most common cancers in the U.S. However, pancreatic cancer's tendency to spread silently before diagnosis makes it the fourth deadliest cancer diagnosis with more than 37,000 people expected to die of the disease in 2012.

Types of Pancreatic Cancer

Pancreatic cancer is classified according to which part of the pancreas is affected: the part that makes digestive substances (exocrine) or the part that makes insulin and other hormones (endocrine).

Exocrine Pancreatic Cancer

Although there are several different types of pancreatic cancer, 95% of cases are due to pancreatic adenocarcinoma.

Other less common exocrine pancreatic cancers include:

Adenosquamous carcinoma
Squamous cell carcinoma
Giant cell carcinoma
Acinar cell carcinoma
Small cell carcinoma
The exocrine pancreas makes up 95% of the pancreas, so it's not surprising that most pancreatic cancers arise here.

Endocrine Pancreatic Cancer

Other cells of the pancreas make hormones that are released directly into the bloodstream (endocrine system). Cancerous tumors arising from these cells are called pancreatic neuroendocrine tumors or islet cell tumors.

Endocrine pancreatic cancers are uncommon, and are named according to the type of hormone produced:

Insulinomas (from an insulin-producing cell)
Glucagonomas (from a glucagon-producing cell)
Somatostatinomas (from a somatostatin-making cell)
Gastrinomas (from a gastrin-producing cell)
VIPomas (from vasoactive intestinal peptide-making cell)
Some pancreatic islet cell tumors do not secrete hormones and are known as non-secreting islet tumors of the pancreas.


Causes of Pancreatic Cancer

Pancreatic cancer occurs when cells in the pancreas grow, divide, and spread uncontrollably, forming a malignant tumor. The exact cause of pancreatic cancer is unknown.

Smoking is the major risk factor for pancreatic cancer. Cigarette smoking roughly doubles the risk for pancreatic cancer when compared to non-smokers. While diabetes is not a risk factor for pancreatic cancer, the two have been linked.

Age, race, and family history are other risk factors for pancreatic cancer.

Prevention of Pancreatic Cancer

There is no known way to prevent pancreatic cancer.

Diagnosis of Pancreatic Cancer

In addition to a history and physical exam, imaging tests will be performed to help make the diagnosis of pancreatic cancer. These tests include:

Ultrasound
CT scanning
Endoscopic ultrasonography
Endoscopic retrograde cholangiopancreatography (ERCP)
A definitive diagnosis of pancreatic cancer only comes from removal of tissue (biopsy). This can be done with a needle through the skin, during endoscopy, or with an operation.

Treatment for Pancreatic Cancer

Pancreatic cancer is treated in several ways, alone or in combination:

Surgery
Chemotherapy
Radiation therapy
Palliative care

Surgery is generally done to attempt to cure pancreatic cancer, but it may also be done to lessen or prevent symptoms. Chemotherapy and radiation are often given together, prior to, after, or even without surgery, to slow pancreatic cancer's growth. Palliative care aims to reduce discomfort for people whose pancreatic cancer cannot be cured.

What to Expect From Pancreatic Cancer
 
Pancreatic cancer is a serious condition. Most cases of pancreatic cancer have already spread at the time of diagnosis, making a full cure unlikely. Treatments can allow people to live longer with pancreatic cancer and improve their quality of life. Clinical trials are ongoing to discover more effective ways of treating pancreatic cancer.

Symptoms

Pancreatic cancer often goes undetected until it's advanced and difficult to treat. In the vast majority of cases, symptoms only develop after pancreatic cancer has grown and begun to spread.

Because more than 95% of pancreatic cancer is the adenocarcinoma type, we'll describe those symptoms first, followed by symptoms of rare forms of pancreatic cancer.


Pancreatic Cancer Symptoms: Location Matters

Initially, pancreatic cancer tends to be silent and painless as it grows. By the time it's large enough to cause symptoms, pancreatic cancer has generally grown outside the pancreas. At this point, symptoms depend on the cancer's location within the pancreas:

Pancreatic cancer in the head of the pancreas tends to cause symptoms such as weight loss, jaundice (yellow skin), dark urine, light stool color, itching, nausea, vomiting, abdominal pain, back pain, enlarged lymph nodes in the neck.
Pancreatic cancer in the body or tail of the pancreas usually causes belly and/or back pain and weight loss.
In general, symptoms appear earlier from cancers in the head of the pancreas, compared to those in the body and tail.

Pancreatic Cancer: Gastrointestinal Symptoms

Because pancreatic cancer grows around important areas of the digestive system, gastrointestinal symptoms often predominate:

Abdominal pain. More than 80% of people with pancreatic cancer eventually experience some abdominal pain as the tumor grows. Pancreatic cancer can cause a dull ache in the upper abdomen radiating to the back. The pain may come and go.
Bloating. Some people with pancreatic cancer have a sense of early fullness with meals (satiety) or an uncomfortable swelling in the abdomen.
Nausea
Diarrhea
Pale-colored stools.
 
If the duct draining bile into the intestine is blocked by pancreatic cancer, the stools may lose their brown color and become pale or clay-colored. Urine may become darker.
Pancreatic Cancer: Constitutional (Whole-Body) Symptoms
As it grows and spreads, pancreatic cancer affects the whole body. Constitutional symptoms can include:

Weight loss
Malaise
Loss of appetite
Elevated blood sugars.

Some people with pancreatic cancer develop diabetes as the cancer impairs the pancreas' ability to produce insulin. (However, the vast majority of people with a new diagnosis of diabetes do not have pancreatic cancer.)

Pancreatic Cancer: Skin Symptoms
 
Jaundice: As pancreatic cancer blocks the duct that releases bile into the intestine (common bile duct), the ingredients of bile build up in the blood. This turns the skin and the eyes yellow, a condition called jaundice. The same blockage causes dark urine and light-colored stools.

Itching: People with pancreatic cancer sometimes report itching all over. Blockage of the bile ducts is often responsible.


Symptoms of Rare Pancreatic Cancers

Islet cell tumors, also called neuroendocrine tumors, arise from the cells in the pancreas that make hormones. Islet cell tumors account for only 1.5% of all pancreas tumors.

Like pancreatic adenocarcinoma, islet cell tumors may cause abdominal pain, weight loss, nausea, and vomiting. Hormones released by an islet cell tumor can also cause symptoms:

Insulinomas (excess insulin): sweating, anxiety, lightheadedness, and fainting from low blood sugar.
Glucagonomas (excess glucagon): diarrhea, excessive thirst or urination, weight loss.
Gastrinomas (excess gastrin): abdominal pain, nonhealing stomach ulcers, reflux, weight loss.
Somatostatinomas (excess somatostatin): diarrhea, weight loss, abdominal pain, foul-smelling fatty stools.
VIPomas (excess vasoactive intestinal peptide): abdominal cramping, watery diarrhea, facial flushing.


Pancreatic Cancer's Sneaky Symptoms
 
In a very small number of people with pancreatic cancer, early symptoms might be present that could lead to an earlier diagnosis. Unfortunately, researchers have been unable to identify any predictable pattern. One study that surveyed 305 people with pancreatic cancer illustrated the challenge:

About 4% reported having a sudden disgust for preferred tastes (like coffee, smoking, or wine) that preceded other symptoms by more than six months.
5% of people had loss of appetite, a feeling of early fullness with meals, or profound weakness, more than six months before more obvious symptoms developed.
1% of people had attacks of acute pancreatitis more than six months before their diagnosis with pancreatic cancer.
The rarity and vagueness of these situations points out the difficulty of using early symptoms to catch pancreatic cancer at an earlier stage.

That said, symptoms like weight loss, persistent loss of appetite, yellowing of the eyes or skin, dark urine, or light-colored stools should always prompt concern. Consistent or worsening discomfort, nausea, vomiting, or diarrhea are also disconcerting. If you feel something's not right, see your doctor.

Pancreatic Cancer Causes Still Unknown

Pancreatic cancer develops when a cell in the pancreas acquires damage to its DNA that causes it to behave and multiply abnormally. A single cancer cell grows and divides rapidly, becoming a tumor that does not respect normal boundaries in the body. Eventually, cells from the tumor travel elsewhere in the body (metastasize) through the blood or lymphatic system.

No one knows exactly how the process of DNA damage leading to pancreatic cancer occurs. Analyzing pancreatic cancers removed by surgery shows certain mutations that occur in nearly all cases, and others that vary between people.

Some of these mutations happen occur randomly. Others occur in response to things we do or experience in the environment. Some mutations may be inherited. When enough mutations accumulate, a cell becomes malignant and a tumor begins to grow.

Pancreatic Cancer Risk Factors

No one understands the underlying causes of pancreatic cancer, but certain risk factors have been identified. These factors are present more often in people who get pancreatic cancer than in people who don't.

There are multiple pancreatic risk factors, although most are only weakly associated with the disease. Many people with pancreatic cancer don't have any one specific risk factor.

About one in 76 people will develop pancreatic cancer. This represents the average risk of the condition. People with any of the pancreatic risk factors are at slightly higher risk than the general population:

Genetics. Five percent to 10% of people with pancreatic cancer have an immediate family member who also had it. Several different genes have been associated with the increased risk, although no "pancreatic cancer gene" has yet been identified.
Diabetes. People with diabetes are not necessarily more likely to get pancreatic cancer but the two have been linked.
Smoking. Cigarette smoking is well known to increase the risk for pancreatic cancer. The more a person smokes, the higher the risk. Ten years after quitting smoking, the risk returns to about that of someone who never smoked.
Obesity and inactivity. In a study of 88,000 nurses, those who were obese (body mass index higher than 30) were more likely to develop pancreatic cancer. Those who exercised frequently were about half as likely to get pancreatic cancer, compared to those who did not exercise at all.
Diet. A diet high in fat and meat (especially smoked or processed meat) has been linked to pancreatic cancer in animal studies. Eating a healthy diet rich in fruits and vegetables decreased pancreatic cancer risk in other studies. Still other studies suggest there's no identifiable link between diet and pancreatic cancer.
Lycopene and selenium. Studies have shown low levels of these nutrients in some people who developed pancreatic cancer. That's not proof that low levels of lycopene and selenium cause pancreatic cancer, though. Any diet that includes lean meat and red or yellow vegetables should provide adequate lycopene and selenium.
Eliminating your risk factors for pancreatic cancer won't reduce your risk entirely. But eating a healthy diet, keeping a healthy weight, and exercising frequently will improve overall health, and reduce your risk of other health problems.

Diagnosis

Pancreatic cancer may go undetected until it's advanced. By the time symptoms occur, diagnosing pancreatic cancer is usually relatively straightforward. Unfortunately, a cure is rarely possible at that point.

(This section focuses on pancreatic adenocarcinoma, which account for more than 95% of pancreatic cancer. Other forms of pancreatic cancer are mentioned at the end.)

Diagnosing pancreatic cancer usually happens when someone comes to the doctor after experiencing weeks or months of symptoms. Pancreatic cancer symptoms frequently include abdominal pain, weight loss, itching, or jaundice (yellow skin). A doctor then embarks on a search for the cause, using the tools of the trade:

By taking a medical history, a doctor learns the story of the illness, such as the time of onset, nature and location of pain, smoking history, and other medical problems.
During a physical exam, a doctor might feel a mass in the abdomen and notice swollen lymph nodes in the neck, jaundiced skin, or weight loss.
Lab tests may show evidence that bile flow is being blocked, or other abnormalities.
Based on a person's exam, lab tests, and description of symptoms, a doctor often orders an imaging test:

Computed tomography (CT scan): A scanner takes multiple X-ray pictures, and a computer reconstructs them into detailed images of the inside of the abdomen. A CT scan helps doctors make a pancreatic cancer diagnosis.
Magnetic resonance imaging (MRI): Using magnetic waves, a scanner creates detailed images of the abdomen, in particular the area around the pancreas, liver, and gallbladder.
Ultrasound: Harmless sound waves reflected off organs in the belly create images, potentially helping doctors make a pancreatic cancer diagnosis.
Positron emission tomography (PET scan): Radioactive glucose injected into the veins is absorbed by cancer cells. PET scans may help determine the degree of pancreatic cancer spread.
If imaging studies detect a mass in the pancreas, a pancreatic cancer diagnosis is likely, but not definite. Only a biopsy -- taking actual tissue from the mass -- can diagnose pancreatic cancer. Biopsies can be performed in several ways:

Percutaneous needle biopsy: Under imaging guidance, a radiologist inserts a needle into the mass, capturing some tissue. This procedure is also called a fine needle aspiration (FNA).
Endoscopic retrograde cholangiopancreatography (ERCP): A flexible tube with a camera and other tools on its end (endoscope) is put through the mouth to the small intestine, near the pancreas. ERCP can collect images from the area, as well as take a small biopsy with a brush.
Endoscopic ultrasound: Similar to ERCP, an endoscope is advanced near the pancreas. An ultrasound probe on the endoscope locates the mass, and a needle on the endoscope plucks some tissue from the mass.
Laparoscopy is a surgical procedure that uses several small incisions. Using laparoscopy, a surgeon can collect tissue for biopsy, as well as see inside the abdomen to determine if pancreatic cancer has spread. However, laparoscopy has higher risks than other biopsy approaches.
If pancreatic cancer seems very likely, and the tumor appears removable by surgery, doctors may recommend surgery without a biopsy. Early Detection of Pancreatic Cancer
Treating pancreatic cancer is challenging when it's discovered at an advanced stage, as is usually the case. Researchers are seeking methods of early detection, but so far none has proved useful. These methods include:

Blood tests. Certain substances, such as carcinoembryonic antigen (CEA) and CA 19-9, are elevated in people with pancreatic cancer. However, blood tests don't allow for early detection of pancreatic cancer, because these levels may not rise until pancreatic cancer is advanced, if at all.

Endoscopic ultrasound. Some families have multiple members affected by pancreatic cancer. The American Cancer Society says that up to 10% of pancreatic cancers may be caused by inherited DNA changes. Studies are ongoing to see if aggressive screening with endoscopic ultrasound works for early detection of pancreatic cancer in healthy family members. Early results are promising. However, endoscopy is an invasive procedure, so its use is only justified in people already at high risk for pancreatic cancer.

Pancreatic Neuroendocrine Cancers

Pancreatic neuroendocrine tumors arise from a separate group of hormone-producing cells in the pancreas. Like adenocarcinoma, islet cell cancers are generally diagnosed with imaging and biopsy. These types of tumors may cause no symptoms or symptoms related to hormones secreted by the tumor.

Treatment

The best treatment for pancreatic cancer depends on how far it has spread, or its stage. The stages of pancreatic cancer are easy to understand. What is difficult is attempting to stage pancreatic cancer without resorting to major surgery. In practice, doctors choose pancreatic cancer treatments based upon imaging studies , surgical findings, and an individual’s general state of well being.

Understanding Pancreatic Cancer

Stages of Pancreatic Cancer

Stage is a term used in cancer treatment to describe the extent of spread of the cancer. 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 a single layer of cells in 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 centimeters (stage IB).
Stage II: Local spread. Pancreatic cancer has grown outside the pancreas, or has spread to nearby lymph nodes.
Stage III: Wider spread. The tumor has expanded into nearby major blood vessels or nerves but has not metastasized.
Stage IV: Confirmed spread. Pancreatic cancer has spread to distant organs.
Determining pancreatic cancer's stage is often tricky. Imaging tests like CT scans and ultrasound provide some information, but knowing exactly how far pancreatic cancer has spread usually requires surgery.

Since surgery has risks, doctors first determine whether pancreatic cancer appears to be removable by surgery (resectable). Pancreatic cancer is then described as follows:

Resectable: On imaging tests, pancreatic cancer hasn't spread (or at least not far), and a surgeon feels it might all be removable. About 10% of pancreatic cancers are considered resectable when first diagnosed.
Locally advanced (unresectable): Pancreatic cancer has grown into major blood vessels on imaging tests, so the tumor can't safely be removed by surgery.
Metastatic: Pancreatic cancer has clearly spread to other organs, so surgery cannot remove the cancer.
If pancreatic cancer is resectable, surgery followed by chemotherapy or radiation or both may extend survival.

Treating Resectable Pancreatic Cancer

People whose pancreatic cancer is considered resectable may undergo one of three surgeries:

Whipple procedure (pancreaticoduodenectomy): A surgeon removes the head of the pancreas, parts of the stomach and small intestine, some lymph nodes, the gallbladder, and the common bile duct. The remaining organs are reconnected in a new way to allow digestion. The Whipple procedure is a difficult and complicated surgery. Surgeons and hospitals that do the most operations have the best results.

About half the time, once a surgeon sees inside the abdomen, pancreatic cancer that was thought to be resectable turns out to have spread, and thus be unresectable. The Whipple procedure is not completed in these cases. 

Distal pancreatectomy: The tail and/or body of the pancreas are removed, but not the head. This surgery is uncommon for pancreatic cancer because most tumors arising outside the head of the pancreas within the body or tail are unresectable.

Total pancreatectomy: The entire pancreas is surgically removed. Although once considered useful, this operation is uncommon today.

Chemotherapy or radiation therapy or both can also be used in conjunction with surgery for resectable and unresectable pancreatic cancer in order to:

Shrink pancreatic cancer before surgery, improving the chances of resection (neoadjuvant therapy)
Prevent or delay pancreatic cancer from returning after surgery (adjuvant therapy)
Chemotherapy includes cancer drugs that travel through the whole body. Chemotherapy ("chemo") kills pancreatic cancer cells in the main tumor as well as those that have spread widely. Either of three chemotherapy drugs can be used for pancreatic cancer:

5-fluorouracil (5-FU) or capecitabine
Gemcitabine
Both 5-FU and gemcitabine are given into the veins during regular visits to an oncologist (cancer doctor). An oral drug, capecitabine, may be substituted for 5-FU, especially with radiation.

In radiation therapy, a machine beams high-energy X-rays to the pancreas to kill pancreatic cancer cells. Radiation therapy is done during a series of daily treatments, usually over a period of weeks.

Both radiation therapy and chemotherapy damage some normal cells, along with cancer cells. Side effects can include nausea, vomiting, appetite loss, weight loss, and fatigue as well as toxicity to the blood cells. Symptoms usually cease within a few weeks after radiation therapy is complete.

Treating Locally Advanced (Unresectable) Pancreatic Cancer
In locally advanced pancreatic cancer, surgery can't remove the entire tumor. Since surgery to remove only part of the pancreatic cancer has been shown not to help, nonsurgical therapies are best.

Treatment consists of chemotherapy with or without radiation therapy. Either 5-FU or gemcitabine can extend life in people with locally advanced pancreatic cancer.

Treating Metastatic Pancreatic Cancer

In metastatic pancreatic cancer, surgery is used only for symptom control, such as for pain, jaundice, or gastric outlet obstruction.. Radiation may be used for symptom relief as well.

Gemcitabine is the single most active drug for treating metastatic pancreas cancer. Many studies have been performed to improve on the results of gemcitabine. The latest study,demonstrated that a 4 drug regimen, known as FOLFIRINOX (5-FU/leucovorin/oxaliplatin/irinotecan), is superior to gemcitabine. However due to toxicities, this therapy should be reserved for persons with good activity levels. Other combinations include gemcitabine with erlotinib, gemcitabine with capecitabine gemcitabine with cisplatin, gemcitabine with nab-paclitaxel. .

If an individual progresses on gemcitabine, usual regimens include oxaliplatin with 5-FU or capecitabine or cisplatin with 5-FU or capecitabine. However, efficacy of these regimens is limited.