Pancreatic cancer

Definition

Exocrine pancreatic cancer is a disease in which cancerous cells originate within the tissues of the pancreas that produce digestive juices.

Description

The pancreas is a 6–8 in (15–20 cm) long, slippershaped gland located in the abdomen. It lies behind the stomach, within a loop formed by the small intestine. Other nearby organs include the gallbladder, spleen, and liver. The pancreas has a wide end (head), a narrow end (tail), and a middle section (body). A healthy pancreas is important for normal food digestion and also plays a critical role in the body's metabolic processes. The pancreas has two main functions, and each are performed by distinct types of tissue. The exocrine tissue makes up the vast majority of the gland and secretes fluids into the other organs of the digestive system. The endocrine tissue secretes hormones (like insulin) that are circulated in the bloodstream, and these substances control how the body stores and uses nutrients. The exocrine tissue of the pancreas, comprised mostly of acinar cells and ductal cells, produces pancreatic (digestive) juices. These juices contain several enzymes that help break down proteins and fatty foods. The exocrine pancreas forms an intricate system of channels or ducts, which are tubular structures that carry pancreatic juices to the small intestine where they are used for digestion.

Pancreatic tumors are classified as either exocrine or endocrine tumors depending on which type of tissue they arise from within the gland. Ninety-five percent of pancreatic cancers occur in the tissues of the exocrine pancreas. Ductal adenocarcinomas arise in the cells that line the ducts of the exocrine pancreas and account for 80% to 90% of all tumors of the pancreas. Unless specified, nearly all reports on pancreatic cancer refer to ductal adenocarcinomas. Less common types of pancreatic exocrine tumors include acinar cell carcinoma, cystic tumors that are typically benign but may become cancerous, and papillary tumors that grow within the pancreatic ducts. Pancreatoblastoma is a very rare disease that primarily affects young children. Two-thirds of pancreatic tumors occur in the head of the pancreas, and tumor growth in this area can lead to the obstruction of the nearby common bile duct that empties bile fluid into the small intestine. When bile cannot be passed into the intestine, patients may develop yellowing of the skin and eyes (jaundice) due to the buildup of bilirubin (a component of bile) in the bloodstream. Tumor blockage of bile or pancreatic ducts may also cause digestive problems since these fluids contain critical enzymes in the digestive process. Depending on their size, pancreatic tumors may cause abdominal pain by pressing on the surrounding nerves. Because of its location deep within the abdomen, pancreatic cancer often remains undetected until it has spread to other organs such as the liver or lung. Pancreatic cancer tends to rapidly spread to other organs, even when the primary (original) tumor is relatively small.

Though pancreatic cancer accounts for only 3% of all cancers, it is the fifth most frequent cause of cancer deaths. In 2001, an estimated 29,200 new cases of pancreatic cancer will be diagnosed in the United States. Pancreatic cancer is primarily a disease associated with advanced age, with 80% of cases occurring between the ages of 60 and 80. Men are almost twice as likely to develop this disease than women. Countries with the highest frequencies of pancreatic cancer include the United States, New Zealand, Western European nations, and Scandinavia. The lowest occurrences of the disease are reported in India, Kuwait, and Singapore. African-Americans have the highest incidence of pancreatic cancer of any ethnic group worldwide. Whether this difference is due to diet or environmental factors remains unclear.

— Lata Cherath; Elizabeth Pulcini, M.Sc.

For more information on pancreatic cancer, visit Britannica.com.

Key Terms: Acinar cell, Acinar cell carcinoma, Angiography, Biopsy, Cancer vaccines, Chemotherapy, Ductal adenocarcinoma, Endoscopic retrograde cholangiopancreatography, Endoscopic ultrasonography, Exocrine, Laparoscopic surgery, Pancreatectomy, Radiation therapy.

Definition

Exocrine pancreatic cancer is a disease in which cancerous cells originate within the tissues of the pancreas that produce digestive juices.

Description

The pancreas is a six- to eight-inch long, slippershaped gland located in the abdomen. It lies behind the stomach, within a loop formed by the small intestine. Other nearby organs include the gallbladder, spleen, and liver. The pancreas has a wide end (head), a narrow end (tail), and a middle section (body). A healthy pancreas is important for normal food digestion and also plays a critical role in the body's metabolic processes. The pancreas has two main functions, and each are performed by distinct types of tissue. The exocrine tissue makes up the vast majority of the gland and secretes fluids into the other organs of the digestive system. The endocrine tissue secretes hormones (like insulin) that are circulated in the bloodstream, and these substances control how the body stores and uses nutrients. The exocrine tissue of the pancreas produces pancreatic (digestive) juices. These juices contain several enzymes that help break down proteins and fatty foods. The exocrine pancreas forms an intricate system of channels or ducts, which are tubular structures that carry pancreatic juices to the small intestine where they are used for digestion.

Pancreatic tumors are classified as either exocrine or endocrine tumors depending on which type of tissue they arise from within the gland. Ninety-five percent of pancreatic cancers occur in the tissues of the exocrine pancreas. Ductal adenocarcinomas arise in the cells that line the ducts of the exocrine pancreas and account for 80% to 90% of all tumors of the pancreas. Unless specified, nearly all reports on pancreatic cancer refer to ductal adenocarcinomas. Less common types of pancreatic exocrine tumors include acinar cell carcinoma, cystic tumors that are typically benign but may become cancerous, and papillary tumors that grow within the pancreatic ducts. Pancreatoblastoma is a very rare disease that primarily affects young children. Two-thirds of pancreatic tumors occur in the head of the pancreas, and tumor growth in this area can lead to the obstruction of the nearby common bile duct that empties bile fluid into the small intestine. When bile cannot be passed into the intestine, patients may develop yellowing of the skin and eyes (jaundice) due to the buildup of bilirubin (a component of bile) in the bloodstream. Tumor blockage of bile or pancreatic ducts may also cause digestive problems since these fluids contain critical enzymes in the digestive process. Depending on their size, pancreatic tumors may cause abdominal pain by pressing on the surrounding nerves. Because of its location deep within the abdomen, pancreatic cancer often remains undetected until it has spread to other organs such as the liver or lung. Pancreatic cancer tends to rapidly spread to other organs, even when the primary (original) tumor is relatively small.

Demographics

Though pancreatic cancer accounts for only 3% of all cancers, it is the fifth most frequent cause of cancer deaths. In 2001, an estimated 29,200 new cases of pancreatic cancer will be diagnosed in the United States. Pancreatic cancer is primarily a disease associated with advanced age, with 80% of cases occurring between the ages of 60 and 80. Men are almost twice as likely to develop this disease than women. Countries with the highest frequencies of pancreatic cancer include the U.S., New Zealand, Western European nations, and Scandinavia. The lowest occurrences of the disease are reported in India, Kuwait and Singapore. African Americans have the highest rate of pancreatic cancer of any ethnic group worldwide. Whether this difference is due to diet or environmental factors remains unclear.

Causes and Symptoms

Although the exact cause for pancreatic cancer is not known, several risk factors have been shown to increase susceptibility to this particular cancer, the greatest of which is cigarette smoking. Approximately one-third of pancreatic cancer cases occur among smokers. People who have diabetes develop pancreatic cancer twice as often as non-diabetics. Numerous studies suggest that a family history of pancreatic cancer is another strong risk factor for developing the disease, particularly if two or more relatives in the immediate family have the disease. Other risk factors include chronic (long-term) inflammation of the pancreas (pancreatitis), diets high in fat, and occupational exposure to certain chemicals such as petroleum.

Pancreatic cancer often does not produce symptoms until it reaches an advanced stage. Patients may then present with the following signs and symptoms:

• upper abdominal and/or back pain
• jaundice
• weight loss
• loss of appetite (anorexia)
• diarrhea
• weakness
• nausea

These symptoms may also be caused by other illnesses; therefore, it is important to consult a doctor for an accurate diagnosis.

Diagnosis

Pancreatic cancer is difficult to diagnose, especially in the absence of symptoms, and there is no current screening method for early detection. The most sophisticated techniques available often do not detect very small tumors that are localized (have not begun to spread). At advanced stages where patients show symptoms, a number of tests may be performed to confirm diagnosis and to assess the stage of the disease. Approximately half of all pancreatic cancers are metastatic (have spread to other sites) at the time of diagnosis.

The first step in diagnosing pancreatic cancer is a thorough medical history and complete physical examination. The abdomen will be palpated to check for fluid accumulation, lumps, or masses. If there are signs of jaundice, blood tests will be performed to rule out the possibility of liver diseases such as hepatitis. Urine and stool tests may be performed as well.

Non-invasive imaging tools such as computed tomography (CT) scans and magnetic resonance imaging (MRI) can be used to produce detailed pictures of the internal organs. CT is the tool most often used to diagnose pancreatic cancer, as it allows the doctor to determine if the tumor can be removed by surgery or not. It is also useful in staging a tumor by showing the extent to which the tumor has spread. During a CT scan, patients receive an intravenous injection of a contrast dye so the organs can be visualized more clearly. MRI may be performed instead of CT if a patient has an allergy to the CT contrast dye. In some cases where the tumor is impinging on blood vessels or nearby ducts, MRI may be used to generate an image of the pancreatic ducts.

If the doctor suspects pancreatic cancer and no visible masses are seen with a CT scan, a patient may undergo a combination of invasive tests to confirm the presence of a pancreatic tumor. Endoscopic ultrasound (EUS) involves the use of an ultrasound probe at the end of a long, flexible tube that is passed down the patient's throat and into the stomach. This instrument can detect a tumor mass through high frequency sound waves and echoes. EUS can be accompanied by fine needle aspiration (FNA), where a long needle, guided by the ultrasound, is inserted into the tumor mass in order to take a biopsy sample. Endoscopic retrograde cholangiopancreatography (ERCP) is a technique often used in patients with severe jaundice because it enables the doctor to relieve blockage of the pancreatic ducts. The doctor, guided by endoscopy and x rays, inserts a small metal or plastic stent into the duct to keep it open. During ERCP, a biopsy can be done by collecting cells from the pancreas with a small brush. The cells are then examined under the microscope by a pathologist, who determines the presence of any cancerous cells.

In some cases, a biopsy may be performed during a type of surgery called laparoscopy, which is done under general anesthesia. Doctors insert a small camera and instruments into the abdomen after a minor incision is made. Tissue samples are removed for examination under the microscope. This procedure allows a doctor to determine the extent to which the disease has spread and decide if the tumor can be removed by further surgery.

An angiography is a type of test that studies the blood vessels in and around the pancreas. This test may be done before surgery so that the doctor can determine the extent to which the tumor invades and interacts with the blood vessels within the pancreas. The test requires local anesthesia and a catheter is inserted into the patient's upper thigh. A dye is then injected into blood vessels that lead into the pancreas, and x rays are taken.

As of April 2001, doctors at major cancer research institutions such as Memorial Sloan-Kettering Cancer Center in New York were investigating CT angiography, an imaging technique that is less invasive than angiography alone. CT angiography is similar to a standard CT scan, but allows doctors to take a series of pictures of the blood vessels that support tumor growth. A dye is injected as in a CT scan (but at rapid intervals) and no catheter or sedation is required. A computer generates 3D images from the pictures that are taken, and the information is gathered by the surgical team who will develop an appropriate strategy if the patient's disease can be operated on.

Treatment Team

Pancreatic cancer is a complex disease that involves specialists from a variety of medical disciplines. Patients are likely to interact with medical oncologists, gastroenterologists, radiologists, and surgeons to develop a suitable treatment plan. Treatment plans vary depending on the stage of the disease and the overall health of the patient. Cancers of the pancreas frequently cause intense pain by pressing on the surrounding network of nerves in the abdomen; therefore, anesthesiologists who specialize in pain management may play a role in making a patient more comfortable. Obstruction of the intestine or bowel can also be a cause of pain, but is usually relieved through surgery. Patients receiving chemotherapy meet with oncologists who determine the dose schedule and oncology nurses who administer the chemotherapy. Patients who undergo partial or total removal of their pancreas may develop diabetes, and an endocrinologist will prescribe insulin or other medication to help them manage this condition. It is important for patients to get proper nutrition during any treatment for cancer. Patients may wish to consult a nutritionist or dietician to assist them (this may require oral replacement of digestive enzymes).

Clinical Staging, Treatments, and Prognosis

Staging

After cancer of the pancreas has been diagnosed, doctors typically use a TNM staging system to classify the tumor based on its size and the degree to which it has spread to other areas in the body. T indicates the size and local advancement of the primary tumor. Since cancers often invade the lymphatic system before spreading to other organs, regional lymph node involvement (N) is an important factor in staging. M indicates whether the tumor has metastasized (spread) to distant organs. In stage I, the tumor is localized to the pancreas and has not spread to surrounding lymph nodes or other organs. Stage II pancreatic cancer has spread to nearby organs such as the small intestine or bile duct, but not the surrounding lymph nodes. Stage III indicates lymph node involvement, whether the cancer has spread to nearby organs or not. Stage IVA pancreatic cancer has spread to organs near the pancreas such as the stomach, spleen, or colon. Stage IVB is a cancer that has spread to distant sites (liver, lung). If pancreatic cancer has been treated with success and then appears again in the pancreas or in other organs, it is referred to as recurrent disease.

Treatments

Treatment of pancreatic cancer will depend on several factors, including the stage of the disease and the patient's age and overall health status. A combination of therapies is often employed in the treatment of this disease to improve the patient's chances for survival. Surgery is used whenever possible and is the only means by which cancer of the pancreas can be cured. However, less than 15% of pancreatic tumors can be removed by surgery. By the time the disease is diagnosed (usually at Stage III), therapies such as radiation and chemotherapy or both are used in addition to surgery to relieve a patient's symptoms and enhance quality of life. For patients with metastatic disease, chemotherapy and radiation are used mainly as palliative (pain-alleviating) treatments.

Surgery

Three types of surgery are used in the treatment of pancreatic cancer, depending on what section of the pancreas the tumor is located in. A Whipple procedure removes the head of the pancreas, part of the small intestine and some of the surrounding tissues. This procedure is most common since the majority of pancreatic cancers occur in the head of the organ. A total pancreatectomy removes the entire pancreas and the organs around it. Distal pancreatectomy removes only the body and tail of the pancreas. Chemotherapy and radiation may precede surgery (neoadjuvant therapy) or follow surgery (adjuvant therapy). Surgery is also used to relieve symptoms of pancreatic cancer by draining fluids or bypassing obstructions. Side effects from surgery can include pain, weakness, fatigue, and digestive problems. Some patients may develop diabetes or malabsorption as a result of partial or total removal of the pancreas.

RADIATION THERAPY Radiation therapy is sometimes used to shrink a tumor before surgery or to remove remaining cancer cells after surgery. Radiation may also be used to relieve pain or digestive problems caused by the tumor if it cannot be removed by surgery. External radiation therapy refers to radiation applied externally to the abdomen using a beam of high-energy x rays. High-dose intraoperative radiation therapy is sometimes used during surgery on tumors that have spread to nearby organs. Internal radiation therapy refers to the use of small radioactive seeds implanted in the tumor tissue. The seeds emit radiation over a period of time to kill tumor cells. Radiation treatment may cause side effects such as fatigue, tender or itchy skin, nausea, vomiting, and digestive problems.

CHEMOTHERAPY Chemotherapeutic agents are powerful drugs that are used to kill cancer cells. They are classified according to the mechanism by which they induce cancer cell death. Multiple agents are often used to increase the chances of tumor cell death. Gemcitabine is the standard drug used to treat pancreatic cancers and can be used alone or in combination with other drugs, such as 5-fluorouracil (5-FU, or fluorouracil). Other drugs are being tested in combination with gemcitabine in several ongoing clinical trials, specifically irinotecan (CPT-11) and oxaliplatin. Chemotherapy may be administered orally or intravenously in a series of doses over several weeks. During treatment, patients may experience fatigue, nausea, vomiting, hair loss (alopecia), and mouth sores, depending on which drugs are used.

Biological Treatments

Numerous vaccine treatments are being developed in an effort to stimulate the body's immune system into attacking cancer cells. This is also referred to as immunotherapy. Another type of biological treatment involves using a targeted monoclonal antibody to inhibit the growth of cancer cells. The antibody is thought to bind to and neutralize a protein that contributes to the growth of the cancer cells. Investigational treatments such as these may be considered by patients with metastatic disease who would like to participate in a clinical trial. Biological treatments typically cause flu-like symptoms (chills, fever, loss of appetite) during the treatment period.

Prognosis

Unfortunately, cancer of the pancreas is often fatal, and median survival from diagnosis is less than six months, while the five-year survival rate is 4%. This is mainly due to the lack of screening methods available for early detection of the disease. Yet, even when localized tumors can be removed by surgery, patient survival after five years is only 10% to 15%. These statistics demonstrate the aggressive nature of most pancreatic cancers and their tendency to recur. Pancreatic cancers tend to be resistant to radiation and chemotherapy and these modes of treatment are mainly used to relieve pain and tumor burden.

Alternative and Complementary Therapies

Acupuncture or hypnotherapy may be used in addition to standard therapies to help relieve the pain associated with pancreatic cancer. Because of the poor prognosis associated with pancreatic cancer, some patients may try special diets with vitamin supplements, certain exercise programs, or unconventional treatments not yet approved by the FDA. Patients should always inform their doctors of any alternative treatments they are using as they could interfere with standard therapies. As of 2000, the National Cancer Institute (NCI) was funding phase III clinical trials of a controversial treatment for pancreatic cancer that involves the use of supplemental pancreatic enzymes (to digest cancerous cells) and coffee enemas (to stimulate the liver to detoxify the cancer). These theories remain unproven and the study is widely criticized in the medical community. It remains to been seen whether this method of treatment has any advantage over the standard chemotherapeutic regimen in prolonging patient survival or improving quality of life.

Coping With Cancer Treatment

Patients should discuss with their doctors any side effects they experience from treatment. Many drugs are available to relieve nausea and vomiting associated with cancer treatments and for combating fatigue. Special diets or supplements, including pancreatic enzymes, may be recommended if patients are experiencing digestive problems. Insulin or other medication may be prescribed if patients develop diabetes as a result of partial or total removal of their pancreas.

Clinical Trials

A large number of clinical trials are underway to assess the therapeutic effect of new chemotherapy regimens and several new immunotherapies. Gemcitabine is being tested in combination with irinotecan (CPT-11) in patients with metastatic pancreatic disease. Other agents under investigation are DX-8951f and R115777. Some drugs are being tested in combination with radiation therapy or with biological therapies. Two preliminary studies using the vaccine G17DT showed a significant improvement in the survival of patients with advanced pancreatic cancer. The monoclonal antibody cetuximab (IMC-C225) in combination with gemcitabine also showed positive preliminary results. There are trials available for patients with all stages of pancreatic cancer. Patients can find out which trials they are eligible for by talking with their doctors. Information about ongoing trials can be found at . Many treatments given during clinical trials are considered experimental by health insurance companies and may not be covered by certain health plans. Patients should discuss their options with their doctors and health insurance providers.

Prevention

Although the exact cause of pancreatic cancer is not known, there are certain risk factors that may increase a person's chances of developing the disease. Quitting smoking will certainly reduce the risk for pancreatic cancer and many other cancers. The American Cancer Society recommends a diet rich in fruits, vegetables, and dietary fiber in order to reduce the risk of pancreatic cancer. According to the NCI, workers who are exposed to petroleum and other chemicals may be at greater risk for developing the disease and should follow their employer's safety precautions. People with a family history of pancreatic cancer are at greater risk than the general population, as a small percentage of pancreatic cancers are considered hereditary.

Special Concerns

Pain control is probably the single greatest problem for patients with pancreatic cancer. As the cancer grows and spreads to other organs in the abdomen, it often presses on the surrounding network of nerves, which can cause considerable discomfort. In most cases, pain can be alleviated with analgesics or opioids. If medication is not enough, a doctor may inject alcohol into the abdominal nerve area to numb the pain. Surgical treatment of the affected nerves is also an option.

Pancreatic cancer patients frequently have difficulty maintaining their weight because food may not taste good or the pancreas is not releasing enough enzymes needed for digestion. Therefore, supplements of pancreatic enzymes may be helpful in restoring proper digestion. Other nutritional supplements may be given orally or intravenously in an effort to boost calorie intake. However, cachexia (severe muscle breakdown) caused by certain substances that the cancer produces, remains a significant problem to treat.

Patients with pancreatic cancer may experience anxiety and depression during their diagnosis and treatment. Statistics on the prognosis for the disease can be discouraging, however, there are many new treatments on the horizon that may significantly improve the out-come for this disease. Many patients find it helpful to join support groups where they can discuss their concerns with others who are also coping with the illness.

Resources

Books

Teeley, Peter, and Philip Bashe. The Complete Cancer Survival Guide. New York: Doubleday, 2000.

Periodicals

Bornman, P.C., and I.J. Beckingham. "ABC of Diseases of Liver, Pancreas, and Biliary System. Pancreatic Tumours." British Medical Journal 322, no. 7288 (March 24, 2001): 721–3.

Haut, E., A. Abbas, and A. Schuricht. "Pancreatic Cancer: The Role of the Primary Care Physican." Consultant 39, no. 12 (December 1999): 3329.

Parks, R.W., and O.J. Garden. "Ensuring Early Diagnosis in Pancreatic Cancer." Practitioner 244, no. 1609 (April 2000): 336–8, 340–1, 343.

Organizations

CancerNet. National Cancer Institute, 9000 Rockville Pike, Bldg.31, Rm.10A16, Bethesda, Maryland, 20892. (800) 422-6237. .

Hirshberg Foundation for Pancreatic Cancer Research. 375 Homewood Rd., Los Angeles, CA 90049. (310) 472-6310. .

National Pancreas Foundation. PO Box 935, Wexford, PA 15090-0935. .

Pancreatic Cancer Action Network. PO Box 1010, Torrance, CA 90505. (877) 272-6226. .

Other

Johns Hopkins Medical Institutions. [cited July 20, 2005]. .

Memorial Sloan-Kettering Cancer Center. Patient Information on Pancreatic Cancer. [cited July 20, 2005]. .

University of Texas MD Anderson Cancer Center. Pancreatic Tumor Study Group. [cited July 20, 2005]. .

"What You Need To Know About Cancer of the Pancreas." National Cancer Institute. [cited July 20, 2005]. .

Questions to Ask the Doctor

• What is my prognosis?
• What is the standard course of treatment for my cancer at this stage?
• How long will the course of treatment take?
• What side effects will I experience?
• What can be done to relieve my abdominal pain?
• What should I do to prepare for surgery?
• Can you refer me to a nutritionist or dietician?
• Are there any alternative therapies you would recommend?
• Am I eligible to participate in a clinical trial?
• Will my health insurance cover costs associated with a clinical trial?
• Are there any support groups I can join?

—Lata Cherath, Ph.D.; Elizabeth Pulcini, M.Sc.

The noun has one meaning:

Meaning #1: cancer of the pancreas

Pancreatic cancer
Classification and external resources
ICD-10	C25.
ICD-9	157
OMIM	260350
DiseasesDB	9510
MedlinePlus	000236
eMedicine	med/1712
MeSH	D010190

Pancreatic cancer is a malignant neoplasm of the pancreas. Each year in the United States, about 42,470 individuals are diagnosed with this condition and 35,240 die from the disease.^[1] The prognosis is relatively poor but has improved; the three-year survival rate is now about thirty percent (according to the Washington University School of Medicine), but less than 5 percent of those diagnosed are still alive five years after diagnosis. Complete remission is still rather rare.^[2]

About 95% of exocrine pancreatic cancers are adenocarcinomas (M8140/3). The remaining 5% include adenosquamous carcinomas, signet ring cell carcinomas, hepatoid carcinomas, colloid carcinomas, undifferentiated carcinomas, and undifferentiated carcinomas with osteoclast-like giant cells.^[3] Exocrine pancreatic cancers are far more common than endocrine pancreatic cancers (also known as islet cell carcinomas), which make up about 1% of total cases.^[4][5]

Contents 1 Signs and symptoms 1.1 Presentation 2 Causes 2.1 Alcohol 3 Diagnosis 4 Prevention 5 Treatment 5.1 Surgery 5.2 Chemotherapy 6 Prognosis 7 Epidemiology 8 See also 9 References 10 External links

Signs and symptoms

Presentation

Pancreatic cancer is sometimes called a "silent killer" because early pancreatic cancer often does not cause symptoms,^[6] and the later symptoms are usually non-specific and varied.^[6] Therefore, pancreatic cancer is often not diagnosed until it is advanced.^[6] Common symptoms include:

• Pain in the upper abdomen that typically radiates to the back^[6] (seen in carcinoma of the body or tail of the pancreas)
• Loss of appetite and/or nausea and vomiting^[6]
• Significant weight loss
• Painless jaundice (yellow skin/eyes, dark urine)^[6] when a cancer of the head of the pancreas (about 60% of cases) obstructs the common bile duct as it runs through the pancreas. This may also cause pale-colored stool and steatorrhea.
• Trousseau sign, in which blood clots form spontaneously in the portal blood vessels, the deep veins of the extremities, or the superficial veins anywhere on the body, is sometimes associated with pancreatic cancer.
• Diabetes mellitus, or elevated blood sugar levels. Many patients with pancreatic cancer develop diabetes months to even years before they are diagnosed with pancreatic cancer, suggesting that new onset diabetes in an elderly individual may be an early warning sign of pancreatic cancer.^[7]
• Clinical depression has been reported in association with pancreatic cancer, sometimes presenting before the cancer is diagnosed. However, the mechanism for this association is not known.^[8]

Causes

Risk factors for pancreatic cancer include:^[6][9]

• Age (particularly over 60)^[6]
• Male gender
• African-American ethnicity^[6]
• Smoking. Cigarette smoking has a risk ratio of 1.74 with regard to pancreatic cancer; a decade of non-smoking after heavy smoking is associated with a risk ratio of 1.2.^[10]
• Diets low in vegetables and fruits^[11]
• Diets high in red meat^[12]
• Obesity^[13]
• Diabetes mellitus is both risk factor for pancreatic cancer, and, as noted earlier, new onset diabetes can be an early sign of the disease.
• Chronic pancreatitis has been linked, but is not known to be causal. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.
• Helicobacter pylori infection
• Family history, 5–10% of pancreatic cancer patients have a family history of pancreatic cancer. The genes responsible for most of this clustering in families have yet to be identified. Pancreatic cancer has been associated with the following syndromes; autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene and PALB2 gene, Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene, hereditary non-polyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, and the familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene.^[2][14]
• Gingivitis or periodontal disease^[15]

Alcohol

It is controversial whether alcohol consumption is a risk factor for pancreatic cancer. Drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, but "chronic pancreatitis that is due to alcohol doesn't increase risk as much as other types of chronic pancreatitis."^{[clarification needed][16]} Overall, the association is consistently weak and the majority of studies have found no association.^{[17][18][19][20]}

Some studies suggest a relationship,^[21] with risk increasing with increasing amount of alcohol intake.^[22][23] Risk is greatest in heavy drinkers^[24][25][26] mostly on the order of four or more drinks per day.^[27] But there appears to be no increased risk for people consuming up to 30g of alcohol a day,^[20][28] so most of the U.S. consumes alcohol at a level that "is probably not a risk factor for pancreatic cancer."^[26]

Several studies caution that their findings could be due to confounding factors.^[25][29] Even if a link exists, it "could be due to the contents of some alcoholic beverages"^[30] other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk.^[31]

A pooled analysis concluded, "Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day."^[32]

Diagnosis

Most patients with pancreatic cancer experience pain, weight loss, or jaundice.^[33]

Pain is present in 80 to 85 percent of patients with locally advanced or advanced metastic disease. The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back. It may be intermittent and made worse by eating. Weight loss can be profound; it can be associated with anorexia, early satiety, diarrhea, or steatorrhea. Jaundice is often accompanied by pruritus and dark urine. Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion.

The initial presentation varies according to location of the cancer. Malignancies in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhea, weight loss, and jaundice. The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis (Trousseau sign), or a previous attack of pancreatitis are sometimes noted.

Courvoisier sign defines the presence of jaundice and a painlessly distended gallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstones.

Tiredness, irritability and difficulty eating due to pain also exist. Pancreatic cancer is usually discovered during the course of the evaluation of aforementioned symptoms.

Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer. However, it lacks sensitivity and specificity. When a cutoff above 37 U/mL is used, this marker has a sensitivity of 77% and specificity of 87% in discerning benign from malignant disease. CA 19-9 might be normal early in the course, and could be elevated due to benign causes of biliary obstruction.^[34]

Imaging studies, such as computed tomography (CT scan) can be used to identify the location of the cancer. Endoscopic ultrasound (EUS) is another procedure that can help visualize the location and can serve to guide a percutaneous needle biopsy, which is necessary to establish a definitive diagnosis.^[35]

In the September 2009 issue of the journal Cancer Prevention Research, scientists from the University of Texas M.D. Anderson Cancer Center identified microRNAs associated with pancreatic cancer from blood samples of pancreatic cancer patients, leading to a new and minimally invasive approach to early detection.^[36]

Prevention

According to the American Cancer Society, there are no established guidelines for preventing pancreatic cancer, although cigarette smoking has been reported as responsible for 20–30% of pancreatic cancers.^[37]

The ACS recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains while decreasing red meat intake, although there is no consistent evidence that this will prevent or reduce pancreatic cancer specifically.^[38][39] In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association.^[40] The evidence in support of this lies mostly in small case-control studies.^[11]

In September 2006, a long-term study concluded that taking Vitamin D can substantially cut the risk of pancreatic cancer (as well as other cancers) by up to 50%, but this study needs to evaluate fully the risks, costs and potential benefits of taking Vitamin D.^[41][42][43]

Several studies, including one published on 1 June 2007, indicate that B vitamins such as B12, B6, and folate, can reduce the risk of pancreatic cancer when consumed in food, but not when ingested in vitamin tablet form.^[44][45]

Treatment

Surgery

Treatment of pancreatic cancer depends on the stage of the cancer.^[46] The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas. This procedure involves removing the pancreatic head and the curve of the duodenum together (pancreato-duodenectomy), making a bypass for food from stomach to jejunum (gasto-jejunostomy) and attaching a loop of jejunum to the cystic duct to drain bile (cholecysto-jejunostomy). It can only be performed if the patient is likely to survive major surgery and if the cancer is localized without invading local structures or metastasizing. It can therefore only be performed in the minority of cases.

Spleen-preserving distal pancreatectomy can also be used as a method to remove a cancer running through centre of pancreas; this is invasive surgery, resulting in loss of body and tail.^{[citation needed]} Cancers of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy.^[46] Recently, localized cancers of the pancreas have been resected using minimally invasive (laparoscopic) approaches. ^[47]

After surgery, adjuvant chemotherapy with gemcitabine has in several large randomized studies been shown to significantly increase the 5-year survival (from approximately 10 to 20%), and should be offered if the patient is fit after surgery(Oettler et al. JAMA 2007, Neoptolemos et al. NEJM 2004, Oettler et al. ASCO proc 2007) . There is a study being done currently by Washington University that is using interferon to treat the cancer, and it has boosted survival times somewhat further. Addition of radiation therapy is a hotly debated topic, with groups in the US often favoring the use of adjuvant radiation therapy, while groups in Europe do not, due to the lack of any large randomized studies to show any survival benefit of this strategy.^[48]

Surgery can be performed for palliation, if the malignancy is invading or compressing the duodenum or colon. In that case, bypass surgery might overcome the obstruction and improve quality of life, but it is not intended as a cure.^[35]

Chemotherapy

In patients not suitable for resection with curative intent, palliative chemotherapy may be used to improve quality of life and gain a modest survival benefit. Gemcitabine was approved by the United States Food and Drug Administration in 1998 after a clinical trial reported improvements in quality of life in patients with advanced pancreatic cancer. This marked the first FDA approval of a chemotherapy drug for a non-survival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis. Addition of oxaliplatin (Gem/Ox) conferred benefit in small trials, but is not yet standard therapy.^[49], a recently published study ECOG 6201 failed to show superiority of GEMOX over gemcitabine alone (Poplin et al, JCO 2009, Louvet et al. JCO 2005). Fluorouracil (5FU) may also be included, however no large randomized study has shown significant survival benefit from this addition(Berlin et al. JCO 2002). One sofar unpublished trial has shown a significant benefit from adding capecitabine to gemcitabine (Cunningham et al. ASCO proc 2005),

On the basis of a Canadian led Phase III Randomised Controlled trial involving 569 patients with advanced pancreatic cancer, the US FDA has licensed the use of erlotinib (Tarceva) in combination with gemcitabine as a palliative regimen for pancreatic cancer. This trial compared the action of gemcitabine/erlotinib vs gemcitabine/placebo and demonstrated improved survival rates, improved tumor response and improved progression-free survival rates(Moore et al. JCO 2005). The survival improvement with the combination is on the order of less than four weeks, leading some cancer experts to question the incremental value of adding erlotinib to gemcitabine treatment. New trials are now investigating the effect of the above combination in the adjuvant and neoadjuvant setting.^[50] A trial of anti-angiogenesis agent bevacizumab (Avastin) as an addition to chemotherapy has shown no improvement in survival of patients with advanced pancreatic cancer(Kindler et al.). It may cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.

Prognosis

Patients diagnosed with pancreatic cancer typically have a poor prognosis partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis. Median survival from diagnosis is around 3 to 6 months; 5-year survival is less than 5%.^[51] With 37,170 cases diagnosed in the United States in 2007, and 33,700 deaths, pancreatic cancer has one of the highest fatality rates of all cancers and is the fourth highest cancer killer in the United States among both men and women. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year.^[52]

Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered and it has been suggested that the cancer can also prompt the onset of diabetes and vice versa.^[53] Thus diabetes is both a risk factor for the development of pancreatic cancer and diabetes can be an early sign of the disease in the elderly.

Epidemiology

Age-standardized death from pancreatic cancer per 100,000 inhabitants in 2004.^[54]

     no data      less than 1      1-2      2-3      3-4      4-5      5-6      6-7      7-8      8-9      9-10      10-11      more than 11

See also

• Category:Deaths from pancreatic cancer
• Category:Pancreatic cancer survivors

References

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External links

• Pancreatic Cancer at American Cancer Society
• The Johns Hopkins Pancreatic Cancer Web Site
• Pancreatic Cancer Action Network (PanCAN)
• The Pancreatic Society of Great Britain and Ireland
• The Johns Hopkins Pancreatic Cancer Web Site Discussion Board
• Rare Pancreatic & Neuroendocrine Cancer Support
• Pancreatic Cancer UK
• Confronting Pancreatic Cancer (Pancreatica.org)
• Cancer of the Pancreas (Cancer Supportive Care Program)
• The National Familial Pancreas Tumor Registry
• Pancreatic Cancer Collaborative Registry (PCCR)
• The Lustgarten Foundation For Pancreatic Cancer Research

v • d • e Tumors: digestive system neoplasia (C15-C26/D12-D13, 150-159/211) GI tract Upper GI tract Esophagus Squamous cell carcinoma · Adenocarcinoma Stomach Gastric carcinoma · Signet ring cell carcinoma · Gastric lymphoma (MALT lymphoma) · Linitis plastica Lower GI tract Small intestine Duodenal cancer (Adenocarcinoma) Appendix Carcinoid · Pseudomyxoma peritonei Colon/rectum colorectal polyp: Peutz-Jeghers syndrome · Juvenile polyposis syndrome · Familial adenomatous polyposis/Gardner's syndrome · Cronkhite–Canada disease neoplasm: Adenocarcinoma · Familial adenomatous polyposis · Hereditary nonpolyposis colorectal cancer Anus Squamous cell carcinoma Upper and/or lower Gastrointestinal stromal tumor · Krukenberg tumor (metastatic) Accessory Liver malignant: Hepatocellular carcinoma (Fibrolamellar) · Hepatoblastoma benign: Hepatocellular adenoma · Cavernous hemangioma hyperplasia: Focal nodular hyperplasia · Nodular regenerative hyperplasia Biliary tract bile duct: Cholangiocarcinoma · Klatskin tumor gallbladder: Gallbladder cancer Pancreas exocrine pancreas: Adenocarcinoma · Pancreatic ductal carcinoma Pancreatoblastoma Peritoneum Primary peritoneal cancer digestive system navs: anat of tract,glands,perit,diaphragm/physio/dev, noncongen/congen/congen of d+w/neoplasia, symptoms+signs/eponymous, proc

v • d • e Tumors: endocrine gland neoplasia (C73-C75/D34-D35, 193-194/226-227) Pancreas/ islets of Langerhans neuroendocrine tumors/islet cell carcinoma: α:Glucagonoma · β:Insulinoma · δ:Somatostatinoma · G:Gastrinoma · VIPoma Hypothalamic/ pituitary axes +parathyroid Pituitary Prolactinoma · ACTH-secreting pituitary adenoma · Growth hormone-secreting pituitary adenoma Craniopharyngioma Pituicytoma Thyroid carcinoma: epithelial cell (Papillary, Follicular/Hurthle cell) · parafollicular cell (Medullary) · Anaplastic Thyroid adenoma Parathyroid Parathyroid adenoma · Parathyroid carcinoma Adrenal tumor adrenal cortex (Adrenocortical adenoma, Adrenocortical carcinoma) adrenal medulla (Pheochromocytoma, Neuroblastoma) · see also Paraganglioma Gonads see genital neoplasia Pinealoma Pinealoblastoma · Pineocytoma MEN 1 · 2A · 2B endocrine navs: anat/physio/dev/hormones, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc

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