1 THE PANCREAS The pancreas is located in the abdomen, tucked behind the stomach. between the upper part of your small intestine (duodenum) and the spleen. It is shaped somewhat like a tadpole - fat at one end and slender at the other - and is around 25cm in length. 2 The pancreas serves two distinct and vital functions; 1. The exocrine pancreas Once food has been mulched and partially digested by the stomach, it is pushed into the duodenum (first part of the small intestine). The pancreas helps to digest food, particularly protein. Most of the pancreas is compose of cells called exocrine cells that produce digestive enzymes. Pancreatic enzymes flow from these cells through small ducts into the main pancreatic duct, which leads to the duodenum. Pancreatic juices contain enzymes that only become activated once they reach the duodenum. This is to prevent the protein-digesting enzyme trypsin from 'eating' the protein-based pancreas or its duct. Other enzymes produced by the pancreas include amylase (to break down carbohydrate) and lipase (to break down fats). 3 The exocrine pancreas also makes sodium bicarbonate, which helps to neutralise stomach acid entering the duodenum. 2. The endocrine pancreas The pancreas makes the hormone insulin, which helps to control blood sugar levels. Insulin is manufactured by a small clump of pancreatic cells called the 'islets of Langerhans'. High blood sugar levels prompt the release of insulin, so that the sugars can pass into cells. The endocrine pancreas also makes glucagon, another hormone involved in the regulation of blood sugar. DIAGNOSIS OF PANCREATIC DISEASE Diagnostic methods depend on the disorder under investigation, but may include: General tests - such as blood tests, physical examination and x-rays. Ultrasound - sound waves form a picture of the pancreas. Computerised tomography (CT) scan - a specialised x-ray takes three-dimensional pictures of the pancreas. Magnetic resonance imaging (MRI) - similar to a CT scan, but magnetism is used to build three-dimensional pictures. Endoscopy (ERCP) - a thin telescope is inserted down the throat. This device may be used to inject contrasting dye into the pancreatic duct prior to x-rays. Laparoscopy - the pancreas is examined through a slender instrument inserted into the abdomen. Biopsy - a small tag of pancreatic tissue is taken out with a needle and examined in a laboratory. PANCREATITIS 4 The pancreas plays important roles in both digestion and metabolism. These functions may be affected by pancreatitis, an inflammatory condition that occurs when pancreatic digestive enzymes become active within the gland and attack the pancreas itself. Pancreatitis can be acute — appearing suddenly and lasting for a few days — or it can be chronic, developing gradually and persisting over many years. Both acute and chronic pancreatitis are marked by mild to severe abdominal pain, often with nausea, vomiting and fever. Both can lead to serious complications. Heavy alcohol use and gallstones are the primary causes of pancreatitis, but other factors, including certain medical conditions, some drugs and genetic mutations also can lead to the disorder. Sometimes the cause is never found.. ACUTE PANCREATITIS Acute pancreatitis is inflammation of the pancreas. This is a medical emergency and requires prompt treatment. It occurs when the pancreas suddenly becomes inflamed - the enzymes can't leave the pancreas and so cause irritation and burning. Enzymes may also leech into the abdominal cavity. The two most common causes for pancreatitis are: Drinking too much alcohol Gallstones 5 Other causes include: Medications such as corticosteroids, nonsteroidal anti- inflammatory drugs, thiazides used for blood pressure lowering, antibiotics including tetracyclines and sulphonamides and immunosuppression with azathioprine and 6-mercaptopurine. Increased levels of triglycerides (fats) or calcium in the blood. Viral infections including mumps Damage or trauma to the pancreas Pancreatic cancer Acute pancreatitis comes on suddenly, usually with mild to severe pain in the upper abdomen that may radiate through to the back and occasionally to the chest. The pain may be nearly constant for hours or even days and is likely to be worse with food. Bending forward or curling into a fetal position may provide some temporary relief. Apart from pain the presentation may feature: Nausea and vomiting Fever Rapid pulse Swollen, tender abdomen When severe, dehydration, internal bleeding, low blood pressure or shock DIAGNOSIS If acute pancreatitis is suspected, the doctor will arrange blood tests to look for: Elevated levels of pancreatic enzymes—amylase or lipase Elevated white cell count High blood sugar 6 Elevated liver enzymes and bilirubin Low calcium levels Oxygen status Because laboratory tests can't confirm a diagnosis of acute pancreatitis, the doctor may request an ultrasound or computerized tomography (CT) scan of your abdomen to examine your pancreas and to check for gallstones, a duct problem, or destruction of the gland. You may also have X-rays of your abdomen and chest to rule out other reasons for your symptoms. COMPLICATIONS Severe cases of acute pancreatitis may lead to a number of complications: Infection A damaged pancreas may become infected with bacteria that spread from the bowel into the inflamed pancreas. The infection may also spread to the blood-stream. Signs of infection include fever and an elevated white blood cell count. Pancreatic infections can be fatal without intensive treatment which may include drainage and surgical removal to remove infected and/or dead tissue. Sometimes multiple such operations are needed. Multi-organ failure may also occur. Pseudocysts These are collections of pancreatic fluid and tissue debris that form within the pancreas or in an obstructed duct. If small no specific treatment may be necessary but if large, bleeding or infected then urgent measures are needed. Abscess A collection of pus in or near the pancreas. Treatment involves drainage by needle, catheter or surgery. Respiratory failure Chemicals circulating in the blood can effect lung function, causing the level of oxygen in the blood to fall to low levels. 7 TREATMENT Acute pancreatitis usually requires admission to hospital. Severe cases or those with complications often need admission to an Intensive Care Unit. Treatment goals include controlling the pain, allowing the pancreas to rest, careful fluid balance and maintaining full respiratory function. Because the pancreas goes into action whenever you eat, you won't be able to eat or drink for a few days. Instead, you'll receive fluids and nutrition through a vein (intravenously). Your doctor may also feed you through a tube that's been passed into your stomach and intestine so that it goes past the pancreas. Placing the tube in the bowel beyond the pancreas ensures that the pancreas is not stimulated, yet you can still receive the nutrition you need. When gallstones block the pancreatic duct, your doctor may recommend a procedure to remove the stones. You may eventually need surgery to remove your gallbladder if gallstones continue to pose problems. Mild cases of acute pancreatitis generally improve in a week or less. Moderate to severe cases take longer. 8 CHRONIC PANCREATITIS Chronic pancreatitis means recurring bouts of inflammation, even when known triggers (such as alcohol) are eliminated. Alcoholics are at increased risk of developing this condition. The relentless inflammation eventually damages or destroys parts of the pancreas, reducing its function. Symptoms include digestive upsets and passing fatty, foul-smelling stools. In addition to pain, one may experience the following with chronic pancreatitis: Nausea and vomiting Fever Weight loss, even when appetite and eating habits are normal Oily, malodorous stools resulting from poor digestion and malabsorption of nutrients, particularly fats (steatorrhea) Diabetes DIAGNOSIS Diagnosing chronic pancreatitis can be challenging because some tests may yield normal results. It can also be difficult to distinguish acute from chronic pancreatitis. Even so, certain tests can help rule out other problems and aid in the diagnosis. These include: Blood tests. Stool test. This measures the fat content in feces. Chronic pancreatitis often causes excess fat in the stool because the fat isn't digested and absorbed normally by the small intestine. Pancreatic function test. If there is weight lost or the doctor suspects a malabsorption problem, a pancreatic function test can be used. Several tests exist but are not commonly used. Ultrasound. In standard (external) ultrasound, a wand-like device (transducer) is placed on the body. It emits inaudible 9 sound waves that are reflected to the transducer and then translated into a moving image by a computer. Endoscopic ultrasound may provide images of the pancreas and bile and pancreatic ducts that are superior to those produced by standard ultrasound. ERCP (X-ray of bile and pancreatic ducts). The doctor gently threads an endoscope down the throat and through the stomach to the opening of the bile and pancreatic ducts in the duodenum. A dye passed through a thin, flexible tube (catheter) inside the endoscope allows for X-ray images of the ducts. The complications common to acute pancreatitis can also occur in the chronic form of the disease. In addition, chronic pancreatitis can lead to: Bleeding. Ongoing inflammation and damage to the blood vessels surrounding the pancreas can cause potentially fatal bleeding. Malnutrition and weight loss. Lack of digestive enzymes prevents your body from absorbing nutrients from food. The result is often unintended weight loss and malnutrition. Diabetes. Damage to insulin-producing cells can lead to diabetes, a disease that affects the way your body uses blood sugar. Drug addiction. Because medical treatments for severe pancreatic pain aren't always effective, people with pancreatitis may become addicted to pain medications. Pancreatic cancer. Long-term inflammation of the pancreas increases your risk of pancreatic cancer, one of the most serious of all malignancies. TREATMENT The main goals of treatment for chronic pancreatitis are to help stop alcohol and drug abuse, control pain and improve malabsorption problems. . Pain relief. Unlike acute pancreatitis, in which the pain often disappears within a few days to weeks, chronic pancreatitis pain can 10 linger. However, conventional pain relievers can be ineffective and pose a real risk of addiction. Using potent pancreatic enzymes to treat pain has proved effective for some people. Enzyme therapy works by increasing the levels of enzymes in the duodenum, which in turn decreases the secretion of enzymes by the pancreas. This is thought to reduce secretion pressure — and hence, pain — within the pancreas. For severe pain that can't be controlled, treatment options include surgery to remove damaged tissue or procedures to block pain signals or deaden the nerves transmitting the pain. Enzyme therapy. Enzyme supplements such as pancreatic lipase (Pancrease) can help treat malabsorption problems. By replacing missing enzymes, these tablets help restore normal digestion and improve steatorrhea, leading to weight gain and enhanced well-being. These supplements are generally taken before and during meals and snacks. Dietary changes. Your doctor may recommend eating smaller meals and limiting fats, which will help reduce your need for as many digestive enzymes. Diabetes Chronic pancreatitis can cause diabetes in some people. Treatment usually involves maintaining a healthy diet and getting regular exercise. Some people also need insulin injections, although insulin must be used cautiously because of the risk of low blood sugar (hypoglycemia). Therapy for alcohol dependency. This may be the most important step in treating alcohol-related pancreatitis. In the early stages of the disease, simply stopping drinking may relieve even severe pain. People who don't stop drinking have a significantly higher chance of dying of pancreatitis 11 CANCER OF THE PANCREAS Pancreatic cancer develops when cancerous cells form in the tissues of the pancreas. The pancreas secretes enzymes that aid digestion and hormones that help regulate the metabolism of carbohydrates. Pancreatic cancer spreads rapidly and is seldom detected in its early stages, which is a major reason why it's a leading cause of cancer death. Signs and symptoms may not appear until the disease is quite advanced. By that time, the cancer is likely to have spread to other parts of the body and surgical removal is no longer possible. CLINICAL PRESENTATION Signs and symptoms of pancreatic cancer often don't occur until the disease is advanced. When symptoms do appear, they may include: Upper abdominal pain that may radiate to the middle or upper back. Pain may be constant or intermittent and is often worse after eating or when you lie down. Loss of appetite and unintentional weight loss. Unintended weight loss is a common sign of pancreatic cancer. Weight loss occurs in most types of cancer because cancerous (malignant) cells deprive healthy cells of nutrients, and this is especially true in pancreatic cancer. Jaundice (Yellowing of the skin) About half of people with pancreatic cancer develop jaundice, which occurs when bilirubin, a breakdown product of worn-out blood cells, accumulates in the blood. Normally, bilirubin is eliminated in bile, a fluid produced in the liver. If a pancreatic tumor blocks the flow of bile, excess pigment from bilirubin may turn the skin and the whites of the eyes yellow. In addition, the urine may be dark brown and the stools white or clay- colored. Although jaundice is a common sign of pancreatic cancer, it's more likely to result from other conditions, such as gallstones or hepatitis. 12 Itching. In the later stages of pancreatic cancer, severe itching may develop when high levels of bile acids, another component of bile, accumulate in the skin. Nausea and vomiting. In advanced cases of pancreatic cancer, the tumor may block a portion of the digestive tract, usually the upper portion of the small intestine (duodenum), causing nausea and vomiting. Digestive problems. When cancer prevents pancreatic enzymes from being released into the intestine, there will be problems digesting foods — especially those high in fat. Eventually, this may lead to significant weight loss and even malnutrition TYPES OF PANCREATIC CANCER Most pancreatic tumours originate in the duct cells or in the cells that produce digestive enzymes (acinar cells). Such tumours are called Adeno-carcinomas, These account for nearly 95 percent of pancreatic cancers. Tumours that begin in the islet cells (endocrine tumors) are much less common. When they do occur, they may cause the affected cells to produce too much hormone. For example, tumours in insulin cells (insulinomas) may lead to an overproduction of insulin. While tumours in glucagon cells (glucagonomas) might cause excess amounts of glucagon to be secreted, while Tumors can also develop in the ampulla of Vater — the place where the bile and pancreatic ducts empty into the small intestine. Called ampullary cancers, these tumors often block the bile duct, leading to jaundice. Because even a small tumor can obstruct the bile duct, signs and symptoms of ampullary cancer usually appear earlier than do symptoms of other pancreatic cancers. 13 Why pancreatic cancer occurs Healthy cells grow and divide in an orderly way. This process is controlled by DNA. When DNA is damaged, changes occur. One result is that cells may begin to grow out of control and eventually form a tumour — a mass of malignant cells. Researchers don't know exactly what damages DNA in the vast majority of cases of pancreatic cancer. RISK FACTORS Risk factors include:. Age: Most occur in people older than 65. Sex. More men than women develop pancreatic cancer. Cigarette smoking. Smokers are 2 to 3 times more likely to develop pancreatic cancer than nonsmokers. This is probably the greatest known risk factor for pancreatic cancer, with smoking associated with almost one in three cases of pancreatic cancer. Diabetes. Having diabetes may increase the risk of pancreatic cancer. Insulin resistance or high insulin levels may also be risk factors for pancreatic cancer. Hereditary pancreatitis. Hereditary pancreatitis (HP) is a rare genetic condition marked by recurrent attacks of pancreatitis and has an increased risk of developing pancreatic cancer. Excess weight. People who are very overweight or obese may have a greater risk of developing pancreatic cancer than do people of normal weight. Diet. A diet high in animal fat and low in fruits and vegetables may increase the risk of pancreatic cancer. 14 Chemical exposure. People who work with petroleum compounds, including gasoline and other chemicals, have a higher incidence of pancreatic cancer than people not exposed to these chemicals. DIAGNOSIS Detecting pancreatic cancer in its early stages is difficult. Signs and symptoms usually don't appear until the cancer is large or has spread (metastasized) to other tissues. And because the pancreas is relatively hidden — tucked behind the stomach and inside the loop of duodenum — small tumors can't be seen or felt during routine exams. CA 19-9 is produced by pancreatic cancer cells and can be detected by a blood test. By the time blood levels are high enough to be measured, the cancer is no longer in its early stages. Currently there is no effective screening test for pancreatic cancer. If pancreatic cancer is suspected, the doctor may order: Ultrasound imaging. In this test, a device called a transducer is placed on the upper abdomen. High-frequency sound waves reflect off abdominal tissues and are translated by a computer into moving images of internal organs, including the pancreas. Ultrasound tests are safe and Computerized tomography (CT) scan. This imaging test allows the doctor to visualize the pancreas, in two-dimensional slices. Magnetic resonance imaging (MRI). Instead of X-rays, this test uses a powerful magnetic field and radio waves to create images of the pancreas. Endoscopic retrograde cholangiopancreatiography (ERCP). In this procedure, a thin, flexible tube (endoscope) is gently passed down the throat, through the stomach and into the upper part of the small intestine. The bile ducts are thin tubes that carry bile, a fluid produced in the liver that helps digest fats. These ducts are often the site of pancreatic tumors. A dye is then injected into the ducts through 15 a small hollow tube (catheter) that's passed through the endoscope. Finally, X-rays are taken of the ducts. Endoscopic ultrasound (EUS). In this test, an ultrasound device is passed through an endoscope into the stomach. The device directs sound waves to the pancreas. The images are superior to those produced by standard ultrasound and are particularly useful for detecting small pancreatic tumors. Percutaneous transhepatic cholangiography (PTC). In this test, your doctor carefully inserts a thin needle into the liver. A dye is then injected into the bile ducts in the liver, and a special X-ray machine (fluoroscope) tracks the dye as it moves through the ducts. Biopsy. In this procedure, a small sample of tissue is removed and examined for malignant cells under a microscope. It's the only way to make a definitive diagnosis of cancer. Biopsies of the pancreas and bile ducts can be performed in several ways. If the mass can be reached with a needle, the doctor may choose to perform a fine- needle aspiration (FNA) — a procedure in which a very thin needle is inserted through the skin and into the pancreas. An ultrasound or CT scan is often used to guide the needle's placement. When the needle has reached the tumor, cells are withdrawn and sent to a lab for further study. Tissue samples can also be removed during ERCP or EUS. Laparoscopy. This procedure uses a small, lighted instrument (laparoscope) to view the pancreas and surrounding tissue. The instrument is attached to a television camera and inserted through a small incision in the abdomen. The camera allows the surgeon to clearly see what's happening inside. During laparoscopy, the surgeon can take tissue samples to help confirm a diagnosis of cancer. Laparoscopy may also be used to determine how far cancer has spread. Risks include bleeding and infection and a slight chance of injury to your abdominal organs or blood vessels. 16 STAGING PANCREATIC CANCER Staging tests help determine the size and location of cancer and whether it has spread. They're crucial in helping the doctor determine the most appropriate treatment. Pancreatic cancer may be staged in several ways. Some terms used are: Resectable. All the tumor nodules can be removed. Locally advanced. Because the cancer has spread to tissues around the pancreas or into the blood vessels, it can no longer be completely removed. Metastatic. At this stage, the cancer has spread to distant organs, such as the lungs and liver. COMPLICATIONS The pancreas produces a number of enzymes that break down food so the body can absorb nutrients. Pancreatic tumors often interfere with the production or flow of these enzymes. As a result, the gut cannot easily absorb nutrients, which can leads to diarrhea and weight loss. Other complications of pancreatic cancer include: Problems with glucose metabolism. Tumors that affect the ability of your pancreas to produce insulin can lead to problems with glucose metabolism, including diabetes. Jaundice, sometimes with severe itching. When a pancreatic tumor blocks the bile duct, the thin tube that carries bile the your liver to the duodenum, jaundice(yellowing of the skin and eyes) occurs. The yellow color comes from excess bilirubin. Bile acids may cause intense itching when they build up in the skin. Pain. Large pancreatic tumors may press on surrounding nerves, leading to back or abdominal pain that may sometimes be severe. When medications aren't enough, cutting or injecting alcohol into some of the affected nerves may be an option. 17 Metastasis. This is the most serious complication of pancreatic cancer. The pancreas is surrounded by a number of vital organs, including your stomach, spleen, liver, lungs and intestine. Because pancreatic tumors are rarely discovered in the early stages, they often have time to spread to these organs or to nearby lymph nodes. TREATMENT Treatment for pancreatic cancer depends on the stage and location of the cancer as well as on age, overall health and personal preferences. Especially when cancer is advanced, choosing a treatment plan is a major decision, and it's important that all choices are discussed by the patient and their doctor. The first goal of treatment is always to eliminate the cancer completely. When that isn't possible, the focus may be on preventing the tumor from growing or causing more harm. In some cases, an approach called palliative care may be best. Palliative care refers to treatment aimed not at removing or slowing the disease, but at helping relieve symptoms and making you as comfortable as possible. Surgery The only way to eliminate pancreatic cancer is an operation to completely remove the tumor. Unfortunately, this is possible only in a small percent of people. Once the cancer has spread beyond the pancreas to other organs, lymph nodes or blood vessels, surgery is usually no longer an option. When surgery is possible, the surgeon, depending on the extent and location of the tumor will consider one of the following procedures, Whipple procedure (pancreatoduodenectomy). This procedure involves removing the wide end (head) of the pancreas. To do that, the surgeon must also remove the duodenum, gallbladder and the end of the common bile duct. Sometimes part of thestomach is removed as well. The end of the bile duct and remaining part of the pancreas are then connected to the small intestine so that bile and pancreatic enzymes continue to reach the small intestine. Total pancreatectomy. In this procedure, the surgeon removes your entire pancreas as well as the bile duct, gallbladder and spleen; part 18 of the small intestine and stomach; and most of the lymph nodes in the area. Total pancreatectomy isn't because there doesn't appear to be enough benefit from the procedure to justify the serious risks Distal pancreatectomy. In this procedure, which is primarily used to treat islet cell cancers, only the tail — or the tail and a small portion of the body of your pancreas — is removed. Sometimes the spleen may also be removed. Operations for pancreatic cancer are complex and carry significant risks including infection, bleeding and death. The most successful outcomes generally occur when these procedures are performed in cancer centers by highly experienced surgeons. Radiation therapy Radiation therapy uses high-energy X-rays to destroy cancer cells. Radiation treatments may be recommended before or after cancer surgery, often in combination with chemotherapy. The doctor may recommend a combination of radiation and chemotherapy treatments when the cancer is not suitable for surgery Side effects of radiation therapy may include a burn on the skin similar to sunburn where the radiation enters the body, nausea, vomiting and fatigue. Chemotherapy Chemotherapy uses drugs to help kill cancer cells. Injected into a vein or taken orally, these drugs travel through the bloodstream. For that reason, they're often used to treat cancers that have spread. Chemotherapy, or chemotherapy in combination with radiation, is the usual treatment for pancreatic cancers that have spread to nearby tissues or distant organs. Although chemotherapy won't eliminate the cancer, it may help relieve symptoms. It may also help improve survival when used as an adjuvant therapy after an operation to remove a tumor in the pancreas. Fluorouracil (5-FU) was the only chemotherapy option for people with pancreatic cancer.. Now doctors are having more success with a 19 newer drug, gemcitabine. Doctors are also testing a number of other new medications and new combinations of older medicines. Chemotherapy drugs affect normal cells as well as malignant ones, especially fast-growing cells in the digestive tract and bone marrow. For that reason, side effects — including nausea and vomiting, mouth sores, an increased chance of infection due to a shortage of white blood cells, and fatigue — are common. Palliative procedures If your cancer has spread too far to be completely removed by an operation, the primary goal will be to relieve your signs and symptoms. Treatments that focus on making you more comfortable include: Surgical bypass. Tumors that block the bile duct, pancreatic duct or duodenum can cause pain, digestive difficulties, nausea, vomiting, jaundice and severe itching. To help ease some of these symptoms, a surgeon can reroute the flow of bile by going around (bypassing) the tumor. Stent insertion. When a bypass operation isn't an option, a stainless steel or plastic tube (stent) can be placed in the bile duct to keep it open. Pain management. Tumors pressing on surrounding nerves can cause severe pain, especially in the later stages of the disease. Although pain is a real concern for people with pancreatic cancer, treatment with morphine or similar medications can provide relief in many cases. Long-lasting forms of morphine that need to be taken only once or twice a day may be especially helpful. When medication isn't enough, the doctor may discuss other options, such as cutting some of the nerves that transmit pain signals or injecting alcohol into these nerves to block the sensation of pain. Pancreatic enzyme tablets. By replacing the digestive enzymes your pancreas no longer produces, these tablets can improve the body's ability to absorb nutrients and may help reduce diarrhea and weight loss. Insulin therapy. When pancreatic cancer affects insulin production, insulin injections may be needed to help control blood sugar levels.
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