Overview of Pancreatic Cancer

Symptoms, risk factors, diagnosis, screening and prevention of pancreatic cancer.

Overview of Pancreatic Cancer

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 10/2018

The pancreas is a glandular organ located in the posterior aspect of the abdomen. It lies between the liver and the spleen, and just below and behind the stomach. The pancreas produces digestive enzymes (exocrine function), which are emptied into the small bowel, as well as the hormone insulin (endocrine function), which enters the blood stream.

Adenocarcinoma is a type of cancer that begins in the cells that line the glands and ducts within the pancreas. It accounts for 90% of cancers originating in the pancreas. This treatment overview deals only with adenocarcinoma of the exocrine pancreas, which will be referred to as pancreatic cancer.

Other Exocrine Cancers of the Pancreas

  • Acinar cell carcinoma: a rare cancer of the pancreas that makes too much of the enzyme lipase which is necessary for the digestion of fat. Lipase can be measured in the blood.
  • Papillary mucinous neoplasm (IPMN): grows in the pancreatic ducts.
  • Mucinous cystadenocarcinoma: a rare cancer that is essentially a cyst filled with thick fluid and usually grows in the tail of the pancreas.

There are approximately 53,000 individuals diagnosed with cancer of the pancreas in the United States each year, and approximately 43,000 individuals succumb to the disease annually. The incidence of carcinoma of the pancreas has markedly increased over the past several decades and ranks as the fourth leading cause of cancer death in the United States. Despite the high mortality rate associated with pancreatic cancer, its cause is poorly understood.(1-5)

The treatment of pancreatic cancer may consist of surgery, precision cancer medicines, chemotherapy, and radiation therapy, and is likely to involve several different types of physicians. As newer precision cancer medicines are developed it's extremely important that all patients undergo genomic biomarker testing. Treating physicians may include a gastroenterologist, a surgeon, a medical oncologist, a radiation oncologist, or other specialists. Care must be carefully coordinated between the various treating physicians.

Symptoms & Signs of Pancreatic Cancer

The initial growth of pancreatic cancer occurs within the pancreas and may cause blockage of the pancreatic or biliary ducts and produce jaundice, a condition where the skin turns yellow. In the early stages of pancreatic cancer there are not many noticeable symptoms. Pancreatic cancer symptoms depend on the site of the cancer within the pancreas and it location. As the cancer grows, symptoms may include the following:

  • Jaundice.
  • Light-colored stools or dark urine.
  • Pain in the upper or middle abdomen and back.
  • Weight loss for no known reason.
  • Loss of appetite.
  • Fatigue

Having these symptoms does not necessarily mean a person has pancreatic cancer. Anyone with these symptoms however should see a doctor so that the problem can be caught early.(1-3)

Cause of Pancreatic Cancer

Pancreatic cancer begins when healthy cells acquire a genetic change (mutation) that causes them to turn into abnormal cells. The exact cause of most pancreatic cancers is unknown and about 5-10 percent are thought to be hereditary. (2)

Risk factors for Pancreatic Cancer

A risk factor is anything that increases a person’s chance of developing cancer. Risk factors can influence the development of cancer but most do not directly cause cancer. Many individuals with risk factors will never develop cancer and others with no known risk factors will. Most pancreatic cancers develop sporadically, which means for no known reason. Some pancreatic cancers however are more likely to develop in individuals with certain risk factors that increase an individual’s chance of developing pancreatic cancer.

The following factors may raise a person’s risk for developing pancreatic cancer.(2,3,4,5)

  • A family history of pancreatic cancer.
  • Cigarette smoking.
  • Obesity.
  • Chronic pancreatitis.
  • Advanced age

Diagnosis & Tests for Pancreatic Cancer

Doctors use many tests to find, or diagnose, cancer. They also do tests to learn if cancer has spread to another part of the body from where it started. A biopsy is the only certain way to confirm a diagnosis of cancer. When performing a biopsy, the doctor takes a sample of tissue for testing in a laboratory.(2)

In order to understand the best treatment options available for treatment of pancreatic cancer, it is important to first determine where the cancer has spread in the body. More advanced cancers may invade adjacent organs, such as the liver, bile ducts, and intestine or spread to lymph nodes, the lining of the abdominal cavity, or other organs in the body via the blood system. Pancreatic cancer cells have a propensity to spread via the blood to the liver and, less commonly, to the lungs.

Determining the extent of the spread or the stage of the cancer is of initial importance to determine whether the cancer can be removed surgically. Upon completion of the clinical “staging evaluation,” your physicians will determine whether the cancer can be removed by surgery.(1) The most common surgical procedure is a “Whipple” procedure. During this procedure the surgeon removes a portion of the pancreas, duodenum, stomach, and the entire gallbladder. Recent clinical studies have suggested that surgery is underutilized in patients with early-stage cancer of the pancreas, and that there is an opportunity to improve care of pancreatic cancer patients in the United States by offering surgery to all appropriate patients with early-stage operable disease.(3)

Following surgical removal of pancreatic cancer, a final “pathologic” stage will be determined. If the cancer cannot be removed by surgery, then the results of the clinical staging evaluation will be used to assign a stage. The following diagnostic procedures may be used in the evaluation of pancreatic cancer.

Imaging tests: Tests such as X-rays, CT scans, magnetic resonance imaging (MRI) and positron emission tomography (PET) are used to help determine the stage and whether the cancer has spread.

  • Computed Tomography (CT) Scan: A CT scan is a technique for imaging body tissues and organs, during which X-ray transmissions are converted to detailed images, using a computer to synthesize X-ray data. A CT scan is conducted with a large machine positioned outside the body that can rotate to capture detailed images of the organs and tissues inside the body.
  • Magnetic Resonance Imaging (MRI): MRI uses a magnetic field rather than X-rays, and can often distinguish more accurately between healthy and diseased tissue than a CT. An MRI gives a better picture of cancer located near bone than does CT, does not use radiation, and provides pictures from various angles that enable doctors to construct a three-dimensional image of the cancer.
  • Positron emission tomography (PET): Positron emission tomography scanning is an advanced technique for imaging body tissues and organs. One characteristic of living tissue is the metabolism of sugar. Prior to a PET scan, a substance containing a type of sugar attached to a radioactive isotope (a molecule that emits radiation) is injected into the patient’s vein. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons) that create the production of gamma rays that can be detected by the PET machine to produce a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells.

Endoscopic Retrograde Cholangiopancreatography (ERCP): Pancreatic cancers may cause blockage of the pancreatic and biliary ducts and produce jaundice. A gastroenterologist may attempt to relieve jaundice using a special procedure where a scope is passed through the stomach into the area of the blockage. An ERCP can also be used to sample (biopsy) any suspicious lesions in the area.

Endosonography: Endosonography refers to an ultrasound test performed through an endoscope. Ultrasound tests utilize sound waves to detect different densities of tissue, including cancer. Endoscopic ultrasound may be used to determine the size of the cancer and whether surrounding lymph nodes may be enlarged.

Gastroscopy: A gastroscopy is an examination performed through an endoscope, which is a flexible tube inserted through the esophagus that allows the physician to visualize, photograph and biopsy (sample) the cancer. All patients have a gastroscopy with a biopsy to determine the histology or appearance of the cancer under the microscope.

Laparoscopy: Laparoscopy is a procedure that involves the insertion of an endoscope through a small incision in the abdomen. Laparoscopy is an important tool for staging and has proven to be more reliable than CT scanning in detecting spread of cancer to the liver and the lining of the abdomen (peritoneum).

Stages of Pancreatic Cancer

In order to learn more about the most recent information available concerning the treatment of pancreatic cancer, click on the appropriate stage.

Stage I: Cancer is confined to the pancreas.

Stage II: Cancer may extend to the duodenum, bile ducts, or fat surrounding the pancreas, but does not invade any local lymph nodes.

Stage III: Cancer invades one or more of the local lymph nodes and has extended to major blood vessels.

Stage IV: Cancer has spread to the stomach, bowel, or distant locations in the body, which may include the liver, lungs, bones, or other sites.

Recurrent/Relapsed: The pancreatic cancer has been detected or returned (recurred/relapsed) following an initial treatment.

Genomic or Biomarker Testing-Precision Cancer Medicine

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancers growth. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

  • Germline BRCA - mutated pancreatic cancer accounts for ~7% of all pancreatic cancers and can be treated with a precision cancer medicine known as a PARP inhibitor. BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA. When either of these genes is mutated, or altered DNA damage may not be repaired properly, and the cells are more likely to develop additional genetic alterations that can lead to cancer.(6,7)

Screening & Prevention of Pancreatic Cancer

Information about the prevention of cancer and the science of screening appropriate individuals at high risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.(2)

Over the past several decades, the incidence of pancreatic cancer has been increasing and the disease is now the fifth leading cause of cancer death in the United States. Pancreatic cancer accounts for approximately 2% of all newly diagnosed cancers in the United States each year, but 5% of all cancer deaths. Pancreatic cancer is often called a silent killer because it usually does not cause any recognizable symptoms until it is advanced and has spread outside the pancreas. As a result, the majority of pancreatic cancers are not diagnosed until they have reached advanced stages and are considered incurable.

The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (i.e. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition, meaning a person may be at higher risk for a certain cancer if a family member has that type of cancer.

Heredity or Genetic Factors

Hereditary associations account for only a small fraction of the total number of cases of pancreatic cancer. Only 7 to 8% of patients with pancreatic cancer have one or more family members with pancreatic cancer. Some other inherited syndromes are associated with an increased incidence of pancreatic cancer, including familial adenomatous polyposis, familial atypical multiple mole melanoma and hereditary pancreatitis. Forty percent of patients with hereditary pancreatitis develop pancreatic cancer by the age of 70. The risk of developing pancreatic cancer is approximately 75% if the pattern of inheritance is through the father. Researchers have identified two gene mutations in families with hereditary pancreatitis. This discovery has helped to allow for screening in families with a history of familial pancreatitis.(2)

Environmental or Non-Genetic Factors

Although the causes of pancreatic cancer remain ambiguous, researchers have identified some risk factors that are associated with pancreatic cancer; however, these environmental factors do not account for the majority of cases.

Cigarette Smoking: The most consistent risk factor associated with pancreatic cancer is cigarette smoking. Cigarette smokers are two to three times more likely to develop pancreatic cancer than nonsmokers. Approximately 30% of pancreatic cancers are believed to directly result from smoking.

Age: Research indicates that the risk of pancreatic cancer increases with age. The average age at diagnosis is 70. People under 40 rarely develop pancreatic cancer.

Diet: The results of several clinical studies indicate that individuals who consume a diet high in fat and low in fruits and vegetables and dietary folate may be at an increased risk of pancreatic cancer. Some researchers have reported an association between meat and fish consumption and the risk of pancreatic cancer. This may be related to the carcinogenic and mutagenic effects of heterocyclic aromatic amines present in cooked meat and fish.(5)

Obesity: Research indicates that individuals who are obese are at an increased risk for developing pancreatic cancer. Researchers used data from two United States cohort studies to evaluate the relationship between obesity, physical activity and the risk of pancreatic cancer. The study involved 46,648 men ages 40 to 75 and 117,041 women ages 30 to 55, with10-20 years of follow-up. The results indicated that individuals with a higher body mass index (BMI) had an increased risk of pancreatic cancer compared with individuals with a lower BMI. Furthermore, moderate activity reduced the risk of pancreatic cancer, especially among individuals with a high BMI.

Occupational exposure: Some studies suggest that exposure to petroleum and other chemicals might increase the risk of pancreatic cancer. Petrochemical workers, hairdressers and rubber workers appear to be at an increased risk of pancreatic cancer.

Pancreatitis: Chronic pancreatitis refers to a long-term inflammation of the pancreas. Patients with non-hereditary chronic pancreatitis appear to have an increased incidence of pancreatic cancer; however, the majority of individuals with chronic pancreatitis never develop pancreatic cancer.

Diabetes: There is an increased incidence of pancreatic cancer among patients with diabetes. Individuals with diabetes develop pancreatic cancer twice as often as those who do not have diabetes. Onset of diabetes may herald the appearance of pancreatic cancer, particularly if the diabetes occurs during or beyond age 50. Diabetes is present in 60-80% of patients with pancreatic cancer and the majority of patients were diagnosed within 2 years of the cancer. Patients with diabetes and cancer more often do not have a family history of diabetes. It appears that a subgroup of patients with late onset diabetes who have no family history of diabetes may be at an increased risk. Abnormalities of glucose metabolism in individuals who do not have diabetes are also associated with an increase in pancreatic cancer.

Prevention of Pancreatic Cancer

Cancer is largely a preventable illness. Two-thirds of cancer deaths in the U.S. can be linked to tobacco use, poor diet, obesity, and lack of exercise. All of these factors can be modified. Nevertheless, an awareness of the opportunity to prevent cancer through changes in lifestyle is still under-appreciated.(2)

Since the development of pancreatic cancer is poorly understood, it is difficult to make recommendations for prevention. Currently, the best approach is to avoid the risk factors for this disease and modify diet and lifestyle.

Avoid Smoking: Since cigarette smoking is responsible for 30% of pancreatic cancers, it would be wise to avoid or quit smoking.

Diet: Diet is a fertile area for immediate individual and societal intervention to decrease the risk of developing certain cancers. Numerous studies have provided a wealth of often-contradictory information about the detrimental and protective factors of different foods.

There is convincing evidence that excess body fat substantially increases the risk for many types of cancer. While much of the cancer-related nutrition information cautions against a high-fat diet, the real culprit may be an excess of calories. Studies indicate that there is little, if any, relationship between body fat and fat composition of the diet. These studies show that excessive caloric intake from both fats and carbohydrates lead to the same result of excess body fat. The ideal way to avoid excess body fat is to limit caloric intake and/or balance caloric death in men in the United intake with ample exercise.

It is still important, however, to limit fat intake, as evidence still supports a relationship between cancer and polyunsaturated, saturated and animal fats. Specifically, studies show that high consumption of red meat and dairy products can increase the risk of certain cancers. One strategy for positive dietary change is to replace red meat with chicken, fish, nuts and legumes.

High fruit and vegetable consumption has been associated with a reduced risk for developing at least 10 different cancers. This may be a result of potentially protective factors such as carotenoids, folic acid, vitamin C, flavonoids, phytoestrogens and isothiocyanates. These are often referred to as antioxidants.

There is strong evidence that moderate to high alcohol consumption also increases the risk of certain cancers. One reason for this relationship may be that alcohol interferes with the availability of folic acid. Alcohol in combination with tobacco creates an even greater risk of certain types of cancer.

While researchers have long evaluated the link between diet and all cancers, there also has been research to investigate the link between diet and pancreatic cancer. Recent studies have indicated that reducing intake of well-cooked meat and fish and increasing the intake of fruit and vegetables might be important for preventing pancreatic cancer. In addition, the results of a recent clinical study indicate that a high intake of dietary folate significantly reduces the risk of pancreatic cancer. Some rich sources of dietary folate are leafy greens, turnip greens, dry beans, peas and some fruits and vegetables.

Exercise: Higher levels of physical activity may reduce the incidence of some cancers. According to researchers at Harvard, if the entire population increased their level of physical activity by 30 minutes of brisk walking per day (or the equivalent energy expenditure in other activities), we would observe a 15% reduction in the incidence of colon cancer.

Screening and Early Diagnosis of Pancreatic Cancer

For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in individuals who do not have any symptoms of a cancer but are at high risk for that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection and treatment strategies.(2)

Pancreatic cancer has a high mortality rate because it is difficult to find the disease early. Pancreatic cancer usually does not cause any recognizable symptoms until it is advanced and has spread outside the body. Since the pancreas is deep inside the body, it is difficult to detect tumors during a routine check-up. Currently, there are no screening tests to find this disease early in individuals who have no symptoms.

Currently, computerized tomography (CT) scans are the best way to detect small pancreatic cancers. Endoscopic ultrasound will detect small pancreatic cancers not detected by CT scans. The cancer marker CA 19-9 is sometimes elevated in early cases of pancreatic cancer.

There are no specific recommendations for screening people who are at a high risk for pancreatic cancer. However, one strategy would be to perform a screening CT for persons with familial syndromes associated with an increased risk of pancreatic cancer. In high-risk patients, endoscopic ultrasound is performed if the CT scan is equivocal or negative. A CA 19-9 should be performed on all high-risk patients.

References:

  1. American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017.
  2. https://www.nccn.org/patients/guidelines/pancreatic/files/assets/basic-html/page-1.html#
  3. Silverman DT, Schiffman M, Everhart J, et al.: Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer 80 (11): 1830-7, 1999.]National failure to operate on early stage pancreatic cancer. Annals of Surgery. 2007;246:173-180.
  4. Tersmette AC, Petersen GM, Offerhaus GJ, et al.: Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res 7 (3): 738-44, 2001.
  5. Nöthlings U, Wilkens LR, Murphy SP, et al.: Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst 97 (19): 1458-65, 2005.
  6. World Cancer Research Fund International. Pancreatic cancer statistics. Accessed February 2019 from https://www.wcrf.org/dietandcancer/cancer-trends/pancreatic-cancer-statistics
  7. https://news.cancerconnect.com/pancreatic-cancer/lynparza-first-promising-new-drug-to-treat-pancreatic-cancer-in-years-H6BzHID6FUiWnbz7R-Oe8A/
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