Treatment of pancreatic cancer at an early stage

Steve Jobs died on Wednesday October 5, 2011 at the age of 56 after an eight -year battle with a rare form of pancreatic cancer. Jobs had undergone surgery for pancreatic cancer and also had a liver transplant in recent years. The man who brought the world the Mac computer with a half eaten Apple logo, later marketed the iPhone, iTunes, the  iPod, the iPad and more.

Ralph Steinman, the Canadian-born doctor who was awarded the Nobel Prize in medicine posthumously on Monday october 3, used his landmark research in his own fight against cancer. Steinman was diagnosed with pancreatic cancer four years ago. He had been working as a cell biologist at New York's Rockefeller University, which released a statement Monday saying that his life "was extended using a dendritic-cell based immunotherapy of his own design." The 68-year-old passed away on Friday 7, before the Nobel Prize Award.

The Nobel committee said it was unaware of his death so the decision would stand. The pancreas is a six- to eight-inch long, 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 is 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 tumours are classified as either exocrine or endocrine tumours 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 per cent  to 90 per cent  of all tumours of the pancreas. Less common types of pancreatic exocrine tumours include acinar cell carcinoma, cystic tumours that are typically benign but may become cancerous, and papillary tumours that grow within the pancreatic ducts. Pancreatoblastoma is a very rare disease that primarily affects young children.

Two-thirds of pancreatic tumours occur in the head of the pancreas, and tumour 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 build-up of bilirubin (a component of bile) in the bloodstream. Tumour 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 tumours 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) tumour is relatively small.

Though pancreatic cancer accounts for only three per cent  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 per cent  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)
• diarrhoea
• 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 tumours 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 tumour can be removed by surgery or not. It is also useful in staging a tumour by showing the extent to which the tumour 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 tumour 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 tumour.

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 tumour 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 tumour 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 tumour 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 tumour 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 tumour 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
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).

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 per cent of pancreatic tumours 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 tumour 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 tumour before surgery or to remove remaining cancer cells after surgery. Radiation may also be used to relieve pain or digestive problems caused by the tumour 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 tumours that have spread to nearby organs. Internal radiation therapy refers to the use of small radioactive seeds implanted in the tumour tissue. The seeds emit radiation over a period of time to kill tumour 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 tumour 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.

Alternative & 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.

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 fibre 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.