Map of Pancreatica Walks and Runs

What is Pancreatic Cancer?

The Pancreas

The pancreas is a small, spongy organ which lies just under the curvature of the stomach and deep within the abdomen. The function of the pancreas is a complicated, but one could say that it primarily does two things. It produces enzymes which are useful for the digestion of food AND it secretes hormones which, among other things, help maintain and regulate body sugar levels.

The pancreatic enzymes are produced in cells which are called acinar cells; this part of the pancreas is called the EXOCRINE part of the pancreas. The clumps of acinar cells are found gathered throughout the pancreas; these cells release salts and enzymes into small tributaries which collect and transport this pancreatic fluid. These small creeks eventually gather and coalesce into the river known as the pancreatic duct. This sixteenth-of-an inch wide duct runs from left-to-right along the length of the pancreas, eventually (usually) joining up with the bile duct and emptying its combined digestive contents into the first part of the small bowel (called the duodenum).

Additionally, the pancreas has an ENDOCRINE or hormonal function. For example, inside of specialized groupings of cells called the Islets of Langerhans, the pancreas produces hormones which are secreted directly into the blood stream. These hormones have numerous effects, and will be addressed in a simplistic fashion here. Insulin (produced by so-called beta cells) has effects, among which it lowers the level of glucose in the blood. Glucagon (produced by alpha cells) tends to increase the level of blood sugar. Other hormones, as well as various peptides, are produced by the endocrine pancreas–including also somatostatin, a hormone which inhibits the secretion of insulin.

Pancreatic Cancer

Malignant cancer is a tumor (or growth) in which an aggregation of individual cells begins to grow in a rapid, uncontrolled and abnormal manner; and which may spread by aggressive local extension or by the seeding of other organs through blood vessel channels or via the lymphatic system. There also exist benign tumors which tend to be (but are not always) less serious, which tend to grow more slowly and orderly, and which tend not to spread by colonizing into other parts of the body (this process known as metastasis). Cancer can arise from virtually any kind of cell in the body.

In up to 95% of cases, pancreatic cancer arises from the exocrine portion of the organ. The least common exocrine pancreatic cancer comes from acinar cells. Most of the exocrine tumors (~90%) are from ductal cells–those which line the pancreatic ducts. These tumors are classified as carcinomas, a word that refers to tumors arising from a lining cell. Further, under the microscope, the appearance and arrangement of these carcinoma cells can appear as duct-like (or “adeno”) giving the term adenocarcinoma to this most common form of pancreatic cancer.

About three-quarters of exocrine pancreatic cancer arises in the head and neck of the pancreas (the anatomic parts through which the pancreatic duct runs just before it meets the duodenum). Some of these carcinomas arise in the body of the pancreatic organ, and less than ten percent arise in the tail of the pancreas (the tapering smaller “left” area, closest to the spleen).

It is now understood that cancer is caused by the mutations of a gene which confer increased abnormal growth potential to cells. Genes in which this potential is directly conferred are called oncogenes. Other kinds of genes whose role includes that of preventing this phenomenon from happening are called tumor-suppressor genes. And finally there is a third kind of gene, called DNA-repair genes, the loss of function through mutation which may allow both activated oncogenes and thwarted tumor-suppressor genes to lead to cancer. It is generally believed that more than one mutation, modifying more than one regulatory pathway, is necessary for cancer to occur.

An oncogene called K-ras is found to be altered in up to 95% of ductal adenocarcinomas of the pancreas (what we usually refer to as pancreatic cancer. Common known tumor-suppressor genes which are inactivated by mutation in this kind of pancreatic cancer are the p53 and p16 genes. For example, p53 is inactivated in about 70% of adenocarcinoms of the pancreas. Still other genetic mutations have been found. This area of inquiry is currently a source of a great deal of interest and research, with an eye toward finding effective treatment or earlier diagnosis of pancreatic cancer.

It has been approximated that up to 30% of the changes which initiate cancer of the pancreas are caused by smoking; and that about 10% are secondary to hereditary genetic predisposition. There appears to be a mild correlation between the onset of diabetes and pancreatic cancer, but it is not entirely clear if this is fully a cause or perhaps an effect of the cancer. There does not appear to be a strong correlation between the onset of pancreatic cancer and the drinking of alcohol or of coffee (though these have been issues of some controversy).

Metastasis and endocrine tumors are two topics which are addressed in more detail in later questions. The most common sites of metastasis of pancreatic cancer (adenocarcinoma) are the liver, the peritoneum – which is the thin lining which contains many structures in the abdominal cavity, and the lungs. Cancers of the endocrine portion of the pancreas (neuroendocrine tumors) are less common than exocrine cancer of the pancreas – about two to three thousand cases are diagnosed each year in the U.S.. They are typically referred to as neuroendocrine tumors – or otherwise known as islet cell tumors. Carcinoid tumors are a typically slow growing type of neuroendocrine tumor. Although they arise from the hormone producing area of the organ, neuroendocrine tumors can be either functioning (demonstrating excess hormone secretion which produces symptoms) or non-functioning. Endocrine tumors have a different natural history than the exocrine tumors. As a whole, they tend to be slower growing and have a better prognosis than standard pancreatic cancer. The treatment of neuroendocrine tumors of the pancreas is distinct from that of adenocarcinoma of the pancreas.

This above description of tumor types is somewhat superficial as there really exists a large number of types of pancreatic cancer (many of these are very rare), some of which have shared characteristics and which may be very difficult to classify. The U.S. Armed Forces Institute of Pathology histological classification of pancreatic cancer outlines several kinds of malignant tumors of the exocrine pancreas (including “miscellaneous carcinomas”), further offering a number of sub-classifications of ductal adenocarcinoma alone and even sub-classifications of acinar cell carcinoma. They identify other forms of benign tumors and multiple “borderline” tumor types, described as having uncertain malignant potential. From this, one can perhaps get a better sense of the complexity of the subject.

The Toll of Pancreatic Cancer

Each year more than 40,000 people in the United States are diagnosed with adenocarcinoma of the pancreas and more than twice that in Europe. Most of these people will have passed away by the end of the first year. The incidence of pancreatic cancer increases with age; most people are between the ages of 60 to 80 when they receive the diagnosis. Men have tended to be over-represented, though in recent years the gap between men and women has shrunk, possibly due to increased cigarette smoking among women. In the U.S., pancreatic cancer is 9th or 10th most commonly diagnosed cancer (depending on gender), but the fourth leading cause of cancer death in men and women. The median survival period from the time of diagnosis until demise is arguably the worst of any of the cancers. The median survival for untreated advanced cancer of the pancreas is about 3 1/2 months; with good treatment this increases to about six months, though many will live much longer.

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