Pancreatic Cancer Treatment

What is pancreas?

The pancreas is a pear-shaped gland located in the abdomen between the stomach and the spine. It is about six inches in length and is made up of two major components:

The exocrine component, made up of ducts and acini (small sacs on the end of the ducts), makes enzymes (specialized proteins) that are released into the small intestine to help the body digest and break down food, particularly fats.

The endocrine component of the pancreas is made up of specialized cells lumped together in islands in the organ, called islets of Langerhans. These cells make specific hormones, most importantly insulin, the substance that helps control the amount of sugar in the blood.

How does cancer affect pancreas?

Two types of cancer can affect the pancreas:

The pancreas has three main parts: the head (which is the part closest to the duodenum and the common bile duct), the body (the middle portion), and the tail. Cancer can develop in any of these parts.

The most common, cancer of the exocrine pancreas (hereafter referred to as pancreatic cancer), originates in the pancreatic ducts. The ducts are responsible for carrying pancreatic juice to the intestines. This type of pancreatic cancer is discussed below.

Another type of cancer consists of a group of tumours that originate from the cells that make hormones such as insulin. Like pancreatic juice, these hormones are made by the pancreas, but instead of traveling through the pancreatic ducts, they are secreted directly into the blood. These tumous are collectively referred to as pancreatic endocrine tumors, and are not addressed here. They are also very rare.

What are the risk factors?

A number of factors increase the risk of developing pancreatic cancer including

smoking

chronic pancreatitis (chronic inflammation of the pancreas)

and possibly diabetes mellitus.

What are the signs and symptoms of pancreatic cancer?

Most patients with pancreatic cancer experience pain, weight loss, and/or jaundice (yellowing of the skin).

Pain is common, and is usually felt in the upper abdomen as a dull ache that radiates to the back. It may be intermittent (comes and goes) and it may be worsened by eating.

Weight loss can be profound. Some people lose weight because of loss of appetite, the sensation of felling full after eating only a small amount of food, or diarrhoea. If the pancreatic duct is blocked by the cancer and the pancreatic juice cannot enter the intestines, the stools may seem greasy and tend to float in the toilet bowl because they contain undigested fat.

Jaundice is a sign of high levels of bilirubin (the main component of bile) in the blood. People with jaundice have yellow skin, whites of the eyes, and urine. A build-up of bilirubin in the blood can be caused by cancers in and around the pancreas, which block the ducts that drain bile from the liver into the intestines. As a result, bowel movements may not be a normal brown colour, and instead have a greyish appearance, described as clay-coloured stools.

Symptoms vary depending upon where the pancreatic cancer is located.

Cancers that develop in the head of the pancreas tend to block the drainage of bile from the liver to the intestines, and typically cause jaundice.

In contrast, tumours that arise in the body or tail are less likely to cause jaundice, and more often cause abdominal pain, weight loss, and diarrhoea.

How do you diagnose this cancer?

If a patient’s signs and symptoms suggest the possibility of pancreatic cancer, a number of different tests can be done to help pinpoint the diagnosis. All tests are not needed in every patient.

Ultrasound of the abdomen

Patients with jaundice will typically have an ultrasound as a first step in the diagnostic process. An ultrasound uses sound waves that are transmitted through a wand-like instrument (a transducer) that applied to the abdomen. The purpose of this ultrasound is to determine whether the bile system is blocked, and to identify where the blockage appears to be located.

CT scan

A CT scan uses x-rays and a computer to take detailed cross sectional pictures of the body, and it may be the initial test ordered in patients who have abdominal pain or unexplained weight loss, particularly if the person is not jaundiced. CT scan may reveal a blockage of the bile and/or pancreatic ducts, a mass within the pancreas or in the periampullary area (where the bile duct, pancreas, and duodenum come together), and/or evidence of cancer spread beyond the pancreas (for example, to the liver).

An injection of dye is usually given during the CT to allow the blood vessels surrounding the pancreas to be studied. The nature and extent of blood vessel involvement helps the surgeon to decide whether or not an operation should be performed.

Endoscopic retrograde cholangiopancreatography(ERCP)

ERCP is a dye study that may be used to outline the pancreatic duct system and bile duct system. It is performed by a gastroenterologist by inserting a small tube (called an endoscope) through the esophagus into the stomach, and then threading it through the duodenum to the papilla of Vater. Dye is then injected through the endoscope into the bile and pancreatic ducts.

The ERCP may help to pinpoint the cause of jaundice, but is usually used only if less invasive tests do not provide enough information. An additional benefit of the ERCP is that if a blockage is identified in one of the bile ducts, it may be possible to place a flexible tube or catheter (also called a “stent”) through the area that is blocked. This procedure can relieve the bile duct obstruction, allowing the bile to once again flow into the intestines, and lowering the amount of bilirubin in the blood operation

Percutaneous transhepatic cholangiopancreatography(PTC)

PTC is an alternative way of visualizing the bile ducts to determine where a blockage is located. Instead of threading a tube into the bile system via the esophagus, a specially trained radiologist threads a tube into the bile ducts by inserting a needle into the liver from outside of the body, and then threading a catheter (over the needle) into the hepatic ducts.

Magnetic resonance cholangiopancreatography (MRCP)

MRCP is an MRI focusing on the bile ducts and pancreas. MRI uses magnetic fields and radio waves to produce detailed pictures of the body. It can create a very detailed three dimensional image of the pancreas, biliary ducts, liver, and surrounding blood vessels without the need for injection of dye.

MRCP is sometimes done if an ERCP or PTC is not technically possible, or if the information provided by the ERCP and CT is incomplete and/or confusing.

Endoscopic ultrasound (EUS)

In this test, ultrasound is done from inside the body by placing the ultrasound transducer on the tip of an endoscope which is then passed into the duodenum by going down the esophagus. EUS is sometimes done if a small tumour is suspected, or to get more information about whether a pancreatic tumor can be removed by surgery.

Biopsy

A biopsy refers to the surgical removal of a small piece of tissue for examination under a microscope, looking for evidence of cancer. For patients suspected of having pancreatic cancer, a biopsy can be performed by inserting a biopsy needle into the area of abnormality. The needle can be inserted into a pancreatic tumor through the skin of the abdominal wall under guidance of a CT scan, or as part of an EUS procedure.

Pancreatic cancer staging

Treatment and prognosis for individual cancers depends upon the extent or “stage” of disease. The most commonly used pancreatic cancer staging system is the TNM (“Tumor, nodes, metastases”) system. It is based upon tumour size and how far the cancer has penetrated into the structures surrounding the pancreas, whether the cancer involves lymph nodes adjacent to the pancreas, and whether the cancer has spread to other organs.

These factors are then combined to assign a “stage grouping” from I to IV, with stage I cancers being the earliest and least advanced stage disease and stage IV the most advanced. The final staging of a pancreatic cancer often depends upon the findings during surgery.

How do you treat this cancer?

Several approaches to treatment of pancreatic cancer are available.

For patients whose cancer has not spread significantly and who are strong enough to withstand an operation, doctors will attempt to remove the cancer surgically. Surgery provides the only opportunity for cure. Surgery is not possible in many patients because the disease is often advanced at the time of diagnosis. Only 5 – 10% of pancreatic cancers are suitable for surgery. Many are not because the cancer has either spread to other organs, or cannot be removed because it is lying too close to, or invading a major blood vessel.

In some cases, chemotherapy and/or radiation therapy will be recommended following surgery while in others it may be offered before surgery (termed neoadjuvant therapy). For patients who are not candidates for surgery, radiation and/or chemotherapy may be offered.

Surgical treatment for pancreatic cancer:

Surgery for tumors in the head of the pancreas

The standard operation for tumours located in the head of the pancreas is a Whipple’s procedure (a pancreaticoduodenectomy). In this procedure, the surgeon removes the pancreatic head, the duodenum (first part of the small intestine), part of the jejunum (the next part of the small intestine), the common bile duct, the gallbladder, and part of the stomach.

The basic concept behind the pancreaticoduodenectomy is that the head of the pancreas and the duodenum share the same arterial blood supply (the gastroduodenal artery). These arteries run through the head of the pancreas, so that both organs must be removed if the single blood supply is severed. If only the head of the pancreas were removed it would compromise blood flow to the duodenum, resulting in tissue necrosis.

Pancreaticoduodenectomy (Whipple,sprocedure)

Reconstruction surgery.

In the past, complications and deaths following this operation were high, and cure rates were less than 10 percent. However, more recent results suggest better outcomes:

In experienced hands, the death rate following surgery is less than 4 percent.
The long-term outlook for patients undergoing this surgery varies, depending in part on whether the cancer has affected the lymph nodes. Between 10 and 30 percent of patients undergoing a Whipple’s procedure for pancreatic cancer will be alive and cancer-free five years after the operation.
Surgery for tumours in the body or tail of the pancreas

Because tumours in the body or tail of the pancreas do not cause the same symptoms as those in the head of the pancreas, these cancers tend to be discovered at a later stage, when they are more advanced.

If the patient has a tumour that can be removed surgically, a laparoscopic exploration is usually done first to make sure the cancer has not spread within the abdominal cavity. If surgery is still an option, part of the pancreas is removed, usually along with the spleen. However, long-term outcome for these patients is usually poor.

Adjuvant therapy after surgery

Adjuvant (additional) therapy refers to chemotherapy,radiation, or a combination of both that is recommended for patients who are thought to be at high risk of having cancer reappear (termed a recurrence or a relapse) after a tumour has been removed surgically. Even if the tumour has been completely removed, tiny cancer cells may remain in the body and grow, causing relapse after surgery. For such patients, adjuvant therapy can prevent relapse and prolong survival by eradicating the tiny cancer cells before they have had a chance to grow.

Treatment of locally advanced pancreatic cancer

Locally advanced pancreatic cancer has not yet spread to distant locations in the body, but has extended into surrounding organs or structures, making surgical removal impossible. The best therapy for locally advanced pancreatic cancer is unknown. Options include chemotherapy alone or a combination of radiation therapy with chemotherapy. This approach increases the average survival for patients with locally advanced cancer by about one year compared to no treatment, but rarely results in long-term survival.

CyberKnife

CyberKnife robotic radiosurgery is a relatively new development for pancreatic cancer. Radiosurgery is the use of very accurately targeted highly focused radiation in a few (1 – 5) very large doses with the aim of obliterating a tumour completely. It can only be given to small areas but is a promising therapy for locally advanced inoperable disease or for patients who would otherwise have surgery but are not fit enough.

Chemotherapy

Patients with metastatic pancreatic cancer (stage IV) have a poor prognosis, with survival averaging only three to six months. Chemotherapy may be offered as a means of slowing the spread of the disease or to relieve disease-related symptoms.

Many different chemotherapeutic drugs and drug combinations have been studied. To date, none has consistently been proven to be more effective than single agent Gemcitabine.

How do you treat signs and symptoms?

Treatment for pancreatic cancer may include a number of other therapies to improve disease-related symptoms.

The symptoms that are most often treated include jaundice, bowel obstruction, pain, and weight loss.

Jaundice is caused by an obstruction of the flow of bile through the common bile duct into the intestine. The most common treatment is the placement of a stent, which is a small tubular device that is inserted into a duct to keep it open. The stent can usually be placed through an endoscope during an ERCP procedure. Initially, a plastic stent is placed, particularly if surgical removal of the cancer is possible. However, plastic stents often get clogged by debris and may become infected and require replacement. Once a decision is made that surgery is not possible, the plastic stent is replaced with a metal one.

If stenting is not possible due to technical reasons, bypass surgery can be done to create a detour around the blockage and restore the drainage of bile. However, this is rarely necessary.

About 15 to 20 percent of patients with pancreatic cancer will develop an obstruction in the duodenum caused by growth of tumour into this part of the small intestine, or from compression from a growing tumour which is outside of the duodenum in the head of the pancreas. A preventive bypass surgery may be performed to create a detour between the stomach and a lower part of the intestine.

Many patients with pancreatic cancer have abdominal pain because the pancreas lies in front of the celiac plexus, the nerve center for many of the abdominal organs. Cancers affecting the pancreas can grow locally and invade this structure, causing severe pain that can be difficult to control. In some patients, medication alone is enough to control the discomfort. Radiation therapy may also help alleviate pain in some cases by shrinking the tumor.

An additional treatment that is being used with increasing frequency is celiac plexus neurolysis (CPN). In this procedure, nerves that transmit pain signals from the area of the tumour are injected with alcohol so that they are unable to transmit signals normally. This procedure can be performed in one of three ways: in the operating theatre at the time of the initial surgical exploration, by a radiologist using a needle that is inserted into the area of the celiac plexus from outside of the body under CT guidance, or through an endoscope by a specially trained gastroenterologist, using endoscopic ultrasound.

Weight loss is common in patients with pancreatic cancer. There can be many causes. One cause is related to a decrease in the absorption of food due to a lack of the pancreatic enzymes that are found in pancreatic juice. Some patients benefit from taking pancreatic enzyme replacement. Other causes of weight loss, such as vomiting or depression, can also be addressed and treated.