What are pancreatic cancers?

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Malignant tumors occurring anywhere in the pancreas, an organ behind the stomach containing exocrine and endocrine glands.
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Related conditions: Acinar cell carcinoma, insulinoma, gastrinoma, glucoganoma

Definition: Pancreatic cancers are malignant tumors occurring anywhere in the pancreas. The pancreas is an organ behind the stomach containing exocrine and endocrine glands. The exocrine glands, where most pancreatic cancer occurs, release digestive juices, which break down fats, proteins, and carbohydrates, and neutralize stomach acids. The endocrine glands produce insulin and glycogen, hormones used by the body to metabolize, or break down, sugar to use as energy.

Risk factors: Factors implicated in the development of pancreatic cancer include advanced age, diabetes, cigarette smoking, chronic pancreatitis, and a family history of the disease. About two-thirds of patients who develop pancreatic cancer are older than age sixty-five, according to the National Cancer Society's 2014 statistics.

Diabetes and pancreatic cancer have been linked, but it is not clear whether diabetes is a cause or a symptom of pancreatic cancer. The American Cancer Society reported in 2014 that pancreatic cancer is more common in those who have diabetes, especially in those who have type II diabetes.

According to the American Cancer Society in 2014, an estimated 20 to 30 percent of exocrine pancreatic cancer cases can be attributed to cigarette smoking. The cancer-causing chemicals in cigarette smoke are thought to enter the bloodstream and damage the pancreas, creating a two to three times greater risk among smokers.

The role of diet in developing pancreatic cancer is inconclusive, although diets high in fat and processed meats appear to present some increased risk, and diets high in fruit, vegetables, and fiber appear to protect against cancer. Obesity and lack of physical activity are also risk factors, as is occupational exposure to chemicals and pesticides.

Long-term inflammation of the pancreas, or chronic pancreatitis, is a risk factor, but the majority of people with this condition do not develop cancer of the pancreas without the presence of other risk factors. However, having a family history of pancreatitis at a young age has been implicated in the development of pancreatic cancer years later. Individuals who have had peptic ulcer surgery with a partial gastrectomy (partial removal of the stomach) may be at increased risk of developing pancreatic cancer. Helicobacter pylori infection also has been linked to pancreatic cancer.

According to the American Society of Clinical Oncology in 2013, the National Institutes of Health has estimated that the risk of developing pancreatic cancer is increased four to five times for someone who has a first-degree relative with the cancer. Particularly among those with two or more relatives who have had pancreatic cancer, inherited deoxyribonucleic acid (DNA) mutations are believed to play a part. People of Ashkenazi Jewish descent may be at greater risk because of the presence of an inherited mutation in the breast cancer gene BRCA2 (each individual inherits two such genes, one from the mother and one from the father). However, the presence of one defective BRCA2 does not increase an individual’s risk of developing pancreatic cancer in the absence of other genetic and environmental factors.

Further, individuals with a rare hereditary disease, Peutz-Jeghers syndrome, in which affected family members develop polyps from the surface of the intestine, may be at increased risk of developing pancreatic cancer. Individuals with hereditary nonpolyposis colorectal cancer (HNPCC) also may be at increased risk of developing cancer of the pancreas.

Etiology and the disease process: Pancreatic cancer occurs when abnormal cells grow in pancreatic tissue. The vast majority of abnormal cells occur in the ducts carrying pancreatic juices from the exocrine glands. Although the exact cause of pancreatic cancer is not known, inherited or acquired changes in DNA are believed to be behind most cases. Many pancreatic cancers are not detected until they are locally advanced and have invaded the vascular system or have spread to lymph nodes. If the tumor blocks the common bile duct and bile cannot be released into the digestive system, the patient’s skin and whites of the eyes become jaundiced and the urine may become darker. The cancer may spread and cause pain in the upper abdomen and sometimes the back.

Incidence: As of 2014, according to the National Cancer Institute, pancreatic cancer is the fourth-leading cause of cancer death in the United States because it grows aggressively and causes few symptoms in the initial stages. However, it is relatively rare compared with other forms of cancer. About 46,420 new cases were diagnosed in 2014, as compared with 232,670 new cases of breast cancer and 224,210 of lung cancer. According to the American Cancer Society, rates of pancreatic cancer increased slightly throughout the first decade of the 2000s. The National Cancer Institute reported that the incidence rate of pancreatic cancer was 12.3 per 100,000 men and women between the years of 2007 and 2011, although this type of cancer is more prevalent among men than women. The incidence of pancreatic cancer is higher in the African American population than in other racial or ethnic groups in the United States, probably because of the higher rates of obesity, poverty, cigarette smoking, and type II diabetes in this group.

Symptoms: Many people do not experience symptoms of pancreatic cancer until the tumor has spread to the lungs, liver, or lymph nodes. The majority of pancreatic cancers occur in the head of the organ, creating symptoms associated with blockage of this area closest to the bile duct. One common symptom is jaundice, a yellowing of the skin and the whites of the eyes resulting from an accumulation of bilirubin in the blood. At least half of those with pancreatic cancer will experience jaundice. Other symptoms include nausea and diarrhea, a swollen gallbladder or liver, pain in the midback, fatigue, a slow metabolism, light-colored stools, and itchy skin.

The smaller percent of pancreatic cancers occurring in the tail of the pancreas often obstruct the vein draining the spleen, resulting in an enlarged spleen and pressure in varicose veins around the stomach and esophagus. An individual may experience this as pain in the midback, pain in the stomach several hours after a meal, blood clots in the legs, and loss of appetite. Tumors or cystadenocarcinoma affecting the hormone-secreting functions of the pancreas, though rare, can produce symptoms of fatigue, dizziness, chills, diarrhea, or muscle spasms.

If the pancreatic cancer occurs in the islet cells, which produce insulin and other hormones, the cells may produce too much insulin, causing the affected individual to feel dizzy and weak and to experience chills, muscle spasms, and diarrhea. This type of endocrine pancreatic cancer is considered highly treatable.

Screening and diagnosis: A high blood level of cancer antigen 19-9 (CA 19-9), a product released into the blood by pancreatic cancer cells, serves as a marker indicating the presence of a pancreatic tumor. However, this marker is used only to assess response to therapy and not as a screening test.

Because there is no screening test for pancreatic cancer, people should report any sudden onset of abdominal pain, loss of appetite, or unexplained weight change to their physician. If pancreatic cancer is suspected, the physician will palpate for presence of an abdominal tumor and order blood tests that will indicate changes in blood sugar or the presence of anemia. However, the pancreas is hidden behind other organs and cannot be felt during a routine physical exam. A differential diagnosis should rule out any liver-related causes of jaundice.

If a pancreatic tumor is present, diagnostic tests such as ultrasound, computed tomography (CT) scans, and endoscopic retrograde cholangiopancreatography (ERCP), a type of X ray, will be ordered to stage the progression of the disease. An ultrasound has been shown to be more useful than a CT scan in detecting the presence of small tumors. A CT scan can be used to guide a needle in obtaining a biopsy. During a positron emission tomography (PET) scan, a form of sugar that is readily absorbed by cancer cells is injected into the patient’s blood to assess the location and spread of cancer cells. A combination PET/CT scan has been found useful in detecting the spread of cancer that surgery cannot remove, for staging, and even for detecting early-stage cancer. ERCP can be used to examine the pancreatic duct while a tissue biopsy is taken to study the cancer cells. An angiogram can be used to show any blockage or impediment of blood flow in vessels caused by the tumor or abnormality of blood vessels to assess the likelihood of removing the cancer surgically.

If surgery such as a laparoscopy is performed, a biopsy may be taken to determine the location and spread of the disease. Laparoscopy is a diagnostic procedure in which an incision is made in the abdomen and a laparoscope, or lighted tube, is inserted to view the pancreas. Alternatively, the physician may choose to perform a laparotomy, a diagnostic surgical procedure in which a large incision is made to examine organs in the abdomen for extent of disease.

Staging for pancreatic cancer is as follows:

  • Stage IA: Tumor is confined to pancreas and is no larger than 2 centimeters (cm).
  • Stage IB: Tumor is confined to pancreas and is larger than 2 cm.
  • Stage IIA: Cancer has metastasized to nearby organs and tissues but not into large blood vessels or to lymph nodes.
  • Stage IIB: Cancer has metastasized to nearby lymph nodes and may have spread to nearby tissues and organs but not distant sites.
  • Stage III: Cancer has reached blood vessels near the pancreas and may have spread to lymph nodes but not distant sites.
  • Stage IV: Cancer, regardless of tumor size, has metastasized to distant organs, and may also be in tissues near the pancreas or in lymph nodes.

Alternatively, some physicians stage the pancreatic cancer on the basis of the likelihood that the tumor can be removed surgically according to the following stages: resectable (can remove entire tumor); locally advanced, unresectable (wherein complete removal of the tumor is not possible); and metastatic (where the cancer has spread and surgery would be undertaken only to relieve symptoms or complications).

Treatment and therapy: The Whipple procedure, or pancreatectomy, a major surgery with a high risk of complications, is used when it is likely that surgery will cure the individual of the entire pancreatic tumor. The head of the pancreas and parts of the stomach and small intestine, bile duct, and gallbladder are removed. After this surgery, the pancreas is still able to produce insulin and digestive juices. A total pancreatectomy involves removal of the entire pancreas, part of the stomach and small intestine, the common bile duct, and the gallbladder, spleen, and nearby lymph nodes.

Palliative surgery may relieve pain and complications associated with the impact of the cancer on digestion, particularly blockage of the bile duct. When surgery cannot remove the entire tumor, during the course of an ERCP, a biliary stent is placed to relieve biliary obstruction and allow vessels to move bile. Inserting an endoscopic or percutaneous biliary stent can relieve jaundice, particularly for those with cancer in the head of the pancreas.

Radiation therapy may be administered five times a week for several weeks or months before surgery, after surgery, or as a primary treatment in conjunction with chemotherapy when the cancer is isolated in the pancreas but cannot be removed surgically.

Chemotherapy alone, particularly gemcitabine, is often used for palliative care of metastatic pancreatic cancer that has spread distally to other organs or body parts. Gemcitabine (Gemzar) has resulted in clinical improvement in some of these patients. The use of erlotinib (Tarceva), which stops signals that instruct cancer cells to multiply, in combination with gemcitabine has proved to be more effective than using gemcitabine alone. However, patients must be healthy and functioning well enough to be able to tolerate the side effects of chemotherapy. Common side effects of chemotherapy treatment with gemcitabine include fatigue, lowered production of blood cells, increased incidence of infection, tiredness, breathlessness, and bruising.

Ongoing clinical trials involve a vaccine for pancreatic cancer that is used to treat existing disease by causing an immune response to the pancreatic cancer.

Prognosis, prevention, and outcomes: The mortality rate for pancreatic cancer based on National Cancer Institute data collected between 2007 and 2011 is 10.9 deaths per 100,000 men and women per year. According to the American Society of Clinical Oncology's data for 2013, the overall five-year survival rates for this cancer are 6 percent. The majority of pancreatic cancers are diagnosed when they have already metastasized.

According to the American Cancer Society in 2014, the five-year survival rate following diagnosis for those with cancers of the exocrine pancreas, the most common type, is 12 to 14 percent when the cancer is localized. However, when it has spread to nearby organs and tissues, the survival rate falls to between 3 and 7 percent, and 1 percent when the cancer has spread to distant organs.

Recommendations for preventing pancreatic cancer include health education to reduce tobacco consumption and referring those at increased risk for familial reasons to genetic counseling and possibly genetic testing.

Bibliography

Azmi, Asfar S, ed. Molecular Diagnostics and Treatment of Pancreatic Cancer: Systems and Network Biology Approaches. London: Academic, 2014. Print.

Hassan, M. N., et al. “Risk Factors for Pancreatic Cancer: Case-Control Study.” American Journal of Gastroenterology 102.12 (2007): 2696–2707. Print.

Reber, Howard, ed. Pancreatic Cancer: Pathogenesis, Diagnosis, and Treatment. Totowa: Humana, 1998. Print.

Risch, H. A. “Etiology of Pancreatic Cancer, with a Hypothesis Concerning the Role of N-Nitroso Compounds and Excess Gastric Acidity.” Journal of the National Cancer Institute 9512 (2003): 948–960. Print.

Wiederpass, E., et al. “Occurrence, Trends and Environment Etiology of Pancreatic Cancer.” Scandinavian Journal of Environmental Health 243 (1998): 165–174. Print.

Wolfgang, Christopher L., et al. "Recent Progress in Pancreatic Cancer." CA: A Cancer Journal for Clinicians 63.5 (2013): 318–48. Print.

Yadav, Dhiraj, and Albert B. Lowenfels. "The Epidemology of Pancreatitis and Pancreatic Cancer." Gastroenterology 144.6 (2013): 1252–61. Print.

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