pancreas diseases : Probing the Pancreas

The human pancreas, an elongated, flattened gland behind the stomach, is involved in or affected by a number of diseases, including diabetes mellitus, cystic fibrosis, pancreatitis, and pancreatic cancer. These conditions are diagnosed and treated with products regulated by the Food and Drug Administration.

The pancreas is composed of two major types of tissues:

exocrine tissue (acini), which secretes digestive enzymes via the pancreatic duct into the duodenum (part of the small intestine leading from the stomach)
endocrine tissue (islets of Langerhans), which produces and secretes the hormones insulin and glucagon directly into the blood.
Endocrine tissue contains alpha, beta and delta cells. Beta cells produce insulin and alpha cells produce glucagon. These hormones regulate blood glucose levels. Delta cells secrete the hormone somatostatin, which inhibits insulin and glucagon secretion.
Diabetes

A deficiency of insulin in the body results in diabetes mellitus, which affects about 13 million individuals in the United States. It is characterized by a high blood glucose (sugar) level and glucose spilling into the urine due to a deficiency of insulin. As more glucose concentrates in the urine, more water is excreted, resulting in extreme thirst, rapid weight loss, drowsiness, fatigue, and possibly dehydration. Because the cells of the diabetic cannot use glucose for fuel, the body uses stored protein and fat for energy, which leads to a buildup of acid (acidosis) in the blood. If this condition is prolonged, the person can fall into a diabetic coma, characterized by deep labored breathing and fruity-odored breath.

There are two types of diabetes. In Type I diabetes, formerly called juvenile-onset diabetes, the pancreas cannot produce insulin. People with Type I diabetes must have daily insulin injections. But they need to avoid taking too much insulin because that can lead to insulin shock, which begins with a mild hunger. This is quickly followed by sweating, shallow breathing, dizziness, palpitations, trembling, and mental confusion. As the blood sugar falls, the body tries to compensate by breaking down fat and protein to make more sugar. Eventually, low blood sugar leads to a decrease in the sugar supply to the brain, resulting in a loss of consciousness. Eating a sugary food can prevent insulin shock until appropriate medical measures can be taken.

Type II diabetes, formerly called adult-onset diabetes, can occur at any age. The pancreas can produce insulin, but the cells do not respond to it.

For many years, treatment was insulin therapy for Type I and oral sulfonylureas and/or insulin therapy for Type II.

Metformin (glucophage) was the first antidiabetic drug approved by FDA (May 1995) for the treatment of Type II diabetes since the oral sulfonylureas were introduced in 1984. Metformin promotes the use of insulin already in the blood. This May 1995 approval was followed by the September 1995 approval of another antidiabetic drug, Acarbose (precose), in September 1995. It slows down the digestion and absorption of complex sugars, which reduces blood sugar levels after meals.

Before 1982, insulin was purified from beef or pork pancreas. This was a problem for those diabetics allergic to animal insulin. Researchers produced a synthetic insulin called humulin. Approved by FDA in 1982, it was the first genetically engineered consumer health product manufactured for diabetics. Synthetic insulins can be produced in unlimited quantities.

Another possible treatment for diabetes includes surgically replacing the pancreas' endocrine tissues (islets of Langerhans) with healthy islet of Langerhans tissue grafts. Since 1988, 45 patients worldwide have undergone successful transplantation.

Cystic Fibrosis

The major problem of cystic fibrosis, the number one genetic killer disease of children in the United States, is that the body overproduces thick, sticky mucus. The mucus blocks the pancreatic ducts, which impedes the flow of the pancreatic juices from the pancreas into the duodenum of the small intestines. Food cannot be properly digested. Without treatment, children with cystic fibrosis suffer from malnutrition and constant diarrhea; their average life expectancy is 21. Pancreatic enzyme preparations are usually used to minimize the disease's effects on the pancreas.

Pancreatic juices contain enzymes for digesting all three major food types (proteins, carbohydrates and fats), as well as quantities of bicarbonate ions, which play an important role in neutralizing the acid emptied by the stomach into the duodenum. The most important enzyme for fat digestion is pancreatic lipase, which is capable of changing fat into glycerol fatty acids and cholesterol. Hormones regulate pancreatic secretions. Food enters the small intestine. The hormones secretin and cholecystokinin cause the pancreas to create large quantities of fluid containing bicarbonate ions, which neutralizes the acid stomach contents.

Pancreatitis

Another common disease associated with the exocrine function of the pancreas is pancreatitis (inflammation of the pancreas), which can be either acute or chronic.

The most common cause of acute pancreatitis is blockage by a gallstone of the main secretory duct from the pancreas as well as the common bile duct. When this happens, large quantities of pancreatic secretions pool in the pancreas and can digest the entire pancreas within a few hours. But because the islets of Langerhans are not adversely affected, the pancreas can continue secreting insulin. Acute pancreatitis is a condition demanding immediate medical attention. It is characterized by abdominal pain, vomiting, abdominal swelling and gas, fever, muscle aches, and a drop in blood pressure. When appropriately treated, the effects of acute pancreatitis usually calm down within five to seven days. Treatment includes stopping oral consumption and providing nourishment only with intravenous fluids.

Chronic pancreatitis occurs when acute pancreatitis continues until pancreatic function is greatly diminished. Symptoms include persistent pain in the upper abdomen which can radiate to the back and last for days or weeks, with mild jaundice (yellow skin and eyes) and rapid weight loss. A person can have recurrent attacks over several years. This may result in secondary bacterial infections of the pancreas, calcium deficiencies, and Type II diabetes.

Pancreatic Cancer

Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, affecting about 27,000 persons yearly. It is second only to colon cancer as a cause of death from gastrointestinal malignancy. It affects men twice as frequently as women and is more likely to develop after the age of 40. Pancreatic cancer risks increase with chronic pancreatitis, diabetes mellitus, genetic factors (more common in blacks than whites), smoking, excess alcohol consumption, high-fat diets, and exposure to industrial chemicals such as urea, naphthalene or benzidine. Symptoms include weight loss, abdominal pain, nausea, loss of appetite, itching, jaundice, and constipation. Abdominal stress may improve or worsen after eating, and the pain may increase after lying down. Because its symptoms mimic many other common health problems, it often goes undetected until it is too late to treat effectively.

When early diagnosis and early treatment are possible, however, survival chances increase. Imaging with endoscopic ultrasound may aid early diagnosis. Researchers are also rapidly building a library of potential genetic markers that indicate the onset of pancreatic cancer. Treatment includes chemotherapeutic drugs and traditional surgical techniques.

The most commonly used chemotherapeutic agents are 5-Fluorouracil (5-FU ) and the recently approved Gemzar (gemcitabine), a nucleoside analog that mimics DNA building blocks. FDA's approval of Gemzar last May was based on two clinical studies in patients with cancer that was locally advanced or had spread beyond the pancreas. These studies found improvement with Gemzar in what is termed "clinical benefit response"--a measure including changes in patients' use of painkillers, pain intensity, and body weight.

The first study, conducted with patients who had never before received chemotherapy, showed that when compared to patients receiving 5-FU therapy, patients treated with Gemzar had a statistically significant improvement in clinical benefit (23.8 percent versus 4.8 percent) and in median survival (5.6 months versus 4.2 months).

A second study conducted in 63 patients previously treated with 5-FU therapy and then given Gemzar showed a clinical benefit response of 27 percent and a median survival of 3.8 months.

Before its approval, FDA authorized Gemzar's manufacturer, Eli Lilly and Company, to make the drug available through a Treatment IND (investigational new drug) program. More than 2,800 patients received the drug under this program between February 1995 and May 1996. Treatment INDs allow drug developers to give patients access to drugs before they are approved for marketing in cases of immediately life-threatening or otherwise serious diseases.

Cryosurgery, a type of surgery in which extremely low temperatures are employed either locally or generally to destroy tissue, is also being investigated for use in pancreatic cancer. The technique involves specific time length and time interval applications by a probe containing liquid nitrogen to freeze the cancer cells to death. The advantages of cryosurgery are that it is inexpensive, requires shorter hospital stays, and causes less blood loss.

Pancreatic diseases are among the most common and most deadly diseases that affect Americans today. Due to genetics and the pancreas' inability to cope with disease, having one pancreatic disease primes the body to contract or develop a second pancreatic disease. Although scientists have made considerable progress in the treatment of diabetes, early detection and treatments for cystic fibrosis and pancreatic cancer don't always guarantee the patient will live a long normal life. However, researchers are constantly searching for new and improved methods to complement or replace current therapies in an attempt to at least improve the patient's quality of life.

Craig D. Reid, a writer in Los Angeles, was diagnosed with cystic fibrosis more than 30 years ago.

by Craig D. Reid, Ph.D.