Pancreatic Cancer

Overview

The pancreas is a digestive organ located in the upper abdomen behind the stomach on a level with the inverted V where the ribs meet at the front. It is about 15cm (6 inches) long. The large rounded section on the right-hand side of the body is called the head of the pancreas, the middle part is known as the body of the pancreas and the narrow part on the left-hand side of the body is called the tail of the pancreas. The head of the pancreas lies next to the first part of the small intestine, which is called the duodenum.

Pancreatitis

Pancreatitis is an inflammatory condition of the pancreas. It may be acute in onset or may be a chronic inflammatory and fibrotic process in which case it is termed as chronic pancreatitis.

Chronic Pancreatitis

Chronic pancreatitis is a long standing inflammation of the pancreas. Pancreas is involved in many functions such as insulin production and synthesis of digestive enzymes. This inflammation leads to loss of these functional capabilities as well as alteration in the structure of pancreas. People with chronic pancreatitis require ongoing medical care to minimize their symptoms, slow the damage to the pancreas, and address any complications that arise. In most cases, treatment controls but does not cure the underlying problem.

Causes

• Exess alcohol consumption
• Hereditary predisposition
• Hyperparathyroidism which causes hypercalcemia (high calcium levels in blood)
• Obstruction of pancreatic duct from stones, tumor etc.
• Hypertriglyceridemia( high fat content in blood)
• Autoimmune causes and use of drugs such as steroids, estrogens, etc.
• In some cases, a cause may not be established.

Symptoms

Chronic pancreatitis is more common in men in the 45-54 yrs age group.

• Pain

Most common symptom of this condition is pain in upper part of abdomen which radiate to the back. Pain at times is excruciating and may be brought upon within 15 - 20 minutes of taking food. It may occur frequently sometimes even 2 -3 times per week or may last 24 hours a day for several days requiring intake of pain killers. Some 20% of patients may never experience any pain at all.

• Loss of pancreatic function

This is manifested by loss of weight, nausea and foul smelling fatty or greasy stools (steatorrhea) which are difficult to flush. This is due to decreased digestion if fat which leads to weight loss and loss of certain vitamins in the body. Patients may also have a high blood sugar level due to lack of insulin production.

Complications of chronic pancreatitis

Chronic pancreatitis can lead to complications like:
Blockage of the ducts that drain the pancreas and gallbladder, leading to jaundice (yellowing of the skin) and bouts of worsening pancreatitis. Blockage of the upper intestine which may cause pain and vomiting leading to further weight loss. 

Diagnostic tests

The signs and symptoms of chronic pancreatitis can be similar to those caused by other health problems, such as an ulcer, gallstones, irritable bowel syndrome, or even pancreatic cancer and hence it can be a tricky and difficult diagnosis to make in the initial one or two years of the disease 

Blood tests

Tests are done to detect pancreatic enzymes in the blood stream like serum amylase and lipase, but it cannot distinguish between an attack of acute pancreatitis and chronic pancreatitis with conviction. Secretic stimulation test may be done but is also not 100% diagnostic. 

Stool test

Fecal estimation of fat and elastase is also done to diagnose fat malabsorption.

The digestive juices produced by the pancreas flow down a tube (the pancreatic duct) into the duodenum. The bile duct drains bile from the liver, into the duodenum, and joins the pancreatic duct at the sphincter of Oddi just as it enters the duodenum.

It has various types of cells grouped into 2 categories-- exocrine cells which produce several digestive enzymes that drain through the pancreatic duct into the duodenum i.e, the first part of the small intestine; and endocrine cells which are specialized cells producing a number of hormones like insulin, glucagon, gastrin etc which are secreted directly into the blood stream. 

Each type can form different cancerous and non cancerous (benign) tumors. In addition, tumors can spread to the pancreas from other organs. Newer advanced imaging techniques, like 64- slice multidetector CT scan, 3-Tesla MRI scanner, Octreotide nuclear scans has helped in acurately diagnosing and staging pancreatic tumors and thus helping in planned surgery which augments favourable outcome.

Exocrine Cell Tumors

Pancreatic exocrine cells commonly arise from the pancreatic duct and form adenocarcinomas which comprise 95% of all pancreatic exocrine cancers. Other less common types of exocrine cell cancers include:

• Mucinous noncystic carcinoma
• Adenosquamous carcinomas
• Mucinous cyst adenocarcinoma
• Intraductal papillary mucinous carcinoma

Our main concern in treating pancreatic cancer revolves around the extent of tumor spread rather than its type. Benign tumors of pancreas include cystadenomas like serous cystadenoma, mucinous cystadenoma, etc.

Endocrine Cell Tumors

Neuroendocrine tumors arise from hormone producing cells (endocrine cells) of the pancreas are more commonly non cancerous than cancerous. They may or may not be hormone producing tumors.

Total Pancreatectomy

• Total pancreatectomy for pancreatic cancer is usually not recommended as the endocrine and exocrine functions of the pancreas are totally lost which result in severe metabolic disturbances.
• Total pancreatectomy may prevent pancreatic fistulas and provide a radical eradication of the tumor.
• The median survival rates are reported to be shorter after total pancreatectomy than after pancreaticoduodenectomy.
• Total pancreatectomy is considered in a few selected patients, e.g. patients with positive resection margins in frozen sections (e.g. IPMN) or tumors not resectable with partial pancreactectomy.
• If total pancreatectomy is opted, retaining the pylorus improves the post surgical outcome.

Distal or caudal pancreatectomy

• When the tumor is located in the left side of the pancreas, a distal or caudal pancreatectomy is considered. Often the tumors that arise in the left region of the pancreas are diagnosed at a very late stage when metastasis has already occurred.
• Resection is a possibility only if the tumor is localised and the celiac axis, the superior mesenteric arteries are not involved. Involvement of splenic vessels is not a contraindication for resection.
• The entire pancreatic body and tail has to be assessed along with the assessment of celiac axis, periaortic region and the peritoneum.
• The spleen is resected in most of the cases after ligating the splenic artery: removal of the spleen assists dissection of the tail. In small and more indolent tumors, spleen resection is a well described procedure with documented benefits.
• The left sided tumors are typically larger in size and lymph nodes are involved to a lesser extent as compared to the right sided tumors.

Pancreaticoduodenectomy

Pancreaticoduodenectomy is performed in patients with tumors in the head, neck, or uncinate process of the pancreas. Recent advances in the surgical techniques and post operative care have improved the outcomes and even long term survival rates. The procedure of pancreaticoduodenectomy is further classified as:

• Kausch-Whipple pancreaticoduodenectomy (Classical Whipple procedure)
• Pylorus preserving pancreaticoduodenectomy (PPPD)

Assessment for resectibility

• The first step in the surgical resection is to rule out distant spread of the disease. The surgeon has to explore for spread of the tumor in the liver, peritoneum, and distant lymph nodes. 

• If the tumor shows involvement in the superior mesenteric artery (SMA), celiac trunk, or hepatic arteries resection is usually not considered while it can be carried out if the superior mesenteric vein (SMV) or the portal vein (PV) is affected. 

• Surgery is considered only if the intraoperative assessment confirms that the tumor is localised in the head, neck and uncinate process of the pancreas. 

• Surgery is considered only if the intraoperative assessment confirms that the tumor is localised in the head, neck and uncinate process of the pancreas. 

• In PPPD, the pylorus is preserved and the duodenum is divided after the pyloric ring. 

• The advantages of PPPD are shorter operative time, minimal effect on the function of pylorus and stomach as a reservoir of food and on the digestive functions of the stomach. 

• Studies have reported that the adverse effects, hospitalisation period, survival time and safety in both the types of resection surgeries are comparable.⁶ PPPD is now a preferred choice for patients with pancreatic adenocarcinoma although level I evidence is lacking.

Remnant pancreas reconstruction

The remnant pancreas is anastomosed either to the jejunum or the stomach to prevent leakage of the pancreatic juices. The anastomotic techniques are:

• Pancreaticojejunostomy
• The duct to mucosa technique is commonly used in pancreaticojejunostomy; a number of variations are described with excellent results.
• Pancreaticogastrostomy
• The procedure involves lodging the pancreatic remnant or the pancreatic duct into the stomach or pancreatic duct into the gastric mucosa.
• The alkaline juices from pancreas may alter gastric pH and affect the gastric mucosa but studies reveal comparable results in terms of survival, complications and recovery with both pancreaticojejunostomy and pancreaticogastrostomy.
• Pancreaticoenteric anastomosis is crucial as it is the single major cause of morbidity and mortality after surgery. The choice of the technique is usually at the surgeon's discretion as it requires expertise and precise implementation.

Reconstruction for biliodigestive continuity

• Gastrojejunostomy is performed after Kausch- Whipple procedure, while a duodenojejunostomy is performed after PPPD.
• Studies have indicated that antrectomy does not have an advantage over PPPD in terms of delayed gastric emptying (DGE). Post surgical complications and extended radical surgery have been found to increase DGE.⁷
• An antecolic duodenojejinostomy is reported to reduce the incidence of post operative DGE.

Pancreas transplant: An insulin-free treatment for type 1 diabetes

A pancreas transplant is a potential cure for advanced type 1 diabetes. Learn what to expect of the transplant process, the surgery itself and follow-up care.

Type 1 diabetes is a condition in which your pancreas produces little or no insulin, a hormone that allows sugar (glucose) to enter your cells. Treatment for type 1 diabetes is a lifelong commitment of monitoring blood sugar, taking insulin, eating healthy foods and maintaining a healthy weight. For some people, however, insulin therapy and healthy lifestyle choices aren't enough.

If you have severe type 1 diabetes that isn't being successfully managed with insulin therapy, you might be a candidate for a pancreas transplant. A successful pancreas transplant may eliminate the need for insulin therapy.

How does the pancreas lose its ability to produce insulin?

The pancreas releases enzymes into your small intestine to break down nutrients. It also releases hormones into your bloodstream to help your body use glucose. One of these hormones, insulin, lets glucose enter your cells. Glucose is a main source of energy for the cells that make up your muscles and other tissues.

Throughout the pancreas are clusters of specialized cells that produce insulin. When you have type 1 diabetes, your immune system — which normally protects you from viruses and bacteria — attacks and kills these cells. This may occur through a combination of factors, including a genetic predisposition or exposure to certain viruses.

Without insulin, glucose can't get into your cells. Lack of insulin can lead to potentially fatal complications. High blood sugar, which can eventually damage your blood vessels and other tissues, is a particular concern. Your eyes, nerves and kidneys are particularly susceptible to this damage.

Who might be considered a candidate for a pancreas transplant?

A pancreas transplant offers a potential cure for type 1 diabetes, but it's not a standard diabetes treatment. Often, the side effects of a pancreas transplant are more serious than the diabetes. If your diabetes treatment plan is working, a pancreas transplant isn't likely a better option. But if your diabetes can't be controlled or you have serious diabetes-related complications, a pancreas transplant may be worthwhile.

The lack of suitable donor pancreases is a major obstacle in the use of pancreas transplants.

Are there different types of pancreas transplants?

If you have frequent insulin reactions or poor blood sugar control and relatively healthy kidneys, your doctor may recommend a pancreas-only transplant. Often, however, a pancreas transplant is combined with a kidney transplant or done after a successful kidney transplant. The strategy is to give you a healthy kidney and a pancreas that's unlikely to contribute to diabetes-related kidney damage in the future.

You might also be a candidate for an islet cell transplant. With this experimental transplant procedure, only the insulin-producing cells from a donor pancreas — not the entire organ — are transplanted into your body.

What should I consider when choosing a transplant center?

If your doctor recommends a pancreas transplant — either alone or combined with a kidney transplant — you may be referred to a transplant center. You're also free to select a transplant center on your own or choose a center from your insurance company's list of preferred providers.

When you're considering transplant centers, ask about the number and type of transplants the center performs each year, as well as its organ and recipient survival rates. You can compare transplant center statistics through a database maintained by the Scientific Registry of Transplant Recipients.

Also consider additional services provided by the transplant center. Many transplant centers coordinate support groups, assist with travel arrangements, help secure local housing for the recovery period and offer referrals to other helpful resources.

Do I need to be accepted by the transplant center?

When you select a transplant center, you'll need an evaluation to determine whether you meet the center's eligibility requirements for a pancreas transplant. The team at the transplant center will assess whether you:

• Are healthy enough to have surgery and tolerate lifelong post-transplant medications
• Have any medical conditions that would hinder transplant success
• Are willing and able to take medications as directed
• Have family and friends to support you during this stressful time

What can I do to prepare for the pancreas transplant?

Whether you're waiting for a donated pancreas to become available or your transplant surgery is already scheduled, it's important to keep your mind and body healthy.

• Take your medications as prescribed.
• Follow your diet and exercise guidelines.
• Keep all appointments with your health care team.
• Stay involved in healthy activities, including relaxing and spending time with family and friends.
• Keep a positive outlook.
• Consider joining a support group.

If you're waiting for a donated pancreas — which can take several years or even longer — make sure the transplant team knows how to reach you at all times. Keep your packed hospital bag handy, and arrange transportation to the transplant center in advance.

What happens during the transplant?

Pancreas transplant surgery usually lasts about three hours. Simultaneous kidney-pancreas transplant surgery takes a few more hours.

The surgeon will place the new pancreas and a small portion of the donor's small intestine into your lower abdomen. The donor intestine will likely be attached to your small intestine, and the donor pancreas will be connected to blood vessels that supply blood to your legs. Your own pancreas will probably be left in place to aid digestion. If you're also receiving a kidney transplant, the blood vessels of the new kidney will be attached to blood vessels in the lower part of your abdomen. The new kidney's ureter — the tube that links the kidney to the bladder — will be connected to your bladder.

Your new pancreas should start working immediately, and your old pancreas will continue to perform its other functions. If you have a new kidney, it'll make urine just like your own kidneys did when they were healthy. Often this starts immediately. In other cases, urine production takes up to a few weeks.

Expect soreness or pain around the incision site while you're healing. Recovery time in the hospital is usually about one week, followed by close monitoring for an additional three to four weeks. During this time, you'll need to stay fairly close to the transplant center.

What can I expect after the transplant?

Even with the best possible match between you and the donor, your immune system will try to reject the new pancreas. Your drug regimen will include medications to suppress your immune system. You'll likely take these or similar drugs for the rest of your life.

Some of these medications may cause noticeable side effects. Steroid-like medications can make your face become round and full. You may gain weight, develop acne or facial hair, or experience abdominal problems. These effects may decrease as time goes on.

Because medications to suppress your immune system make your body more vulnerable to infection, your doctor may also prescribe antibacterial, antiviral and antifungal medications. Some immune system medications can also increase the risk of developing or aggravating certain conditions, such as high blood pressure, high cholesterol and cancer.

Your post-transplant treatment will be a delicate balancing act between preventing rejection and managing unwanted side effects. Your doctor will monitor your treatment closely and adjust it as needed. You'll also need to follow a diet designed to keep your new pancreas healthy.

What are typical survival rates?

A pancreas transplanted along with a kidney is more likely to survive than a pancreas transplanted alone. According to the Organ Procurement and Transplantation Network:

• About 85 percent of people who receive a simultaneous pancreas-kidney transplant have a functioning pancreas after one year. The rate drops to about 70 percent after five years.
• About 78 percent of people who receive a pancreas-after-kidney transplant have a functioning pancreas after one year. The rate drops to about 56 percent after five years.
• About 73 percent of people who receive a pancreas-only transplant have a functioning pancreas after one year. The rate drops to about 53 percent after five years.

What if my new pancreas fails?

A pancreas transplant offers no guarantees. Your new pancreas may fail because of organ rejection or other factors that can't be controlled. If this happens, you can resume insulin treatments and consider a second transplant. This decision will depend on your current health, your ability to withstand surgery and your expectations for maintaining a certain quality of life. Discuss these choices with your doctor, transplant team and family to determine what's best for you.

Via: www.mayoclinic.com

Pancreas Transplantation

Whole pancreas transplantation

In people with type 1 diabetes, the islet cells in the pancreas no longer produce insulin. So it seems logical that giving a new pancreas to a person with type 1 diabetes would cure their disease. Usually it does.

But the cure can be worse than the disease. The body has a complex system for telling its own parts from foreign parts. To fool the body into accepting the donor organ, doctors try to match the donor and recipient for a blood protein called human leukocyte antigen (HLA) type. Patients with a transplanted organ must take immunosuppressive drugs in order to prevent the immune system from fighting the new organ. The side effects of these drugs may be worse than the problems caused by diabetes, and the operation itself is serious. One to two people in 10 die within a year of getting a pancreas transplant. However, there are situations where a person has such severe complications from diabetes that having a pancreas transplant and taking these immunosuppressive drugs is no worse. People with kidney transplants have to use these drugs anyway so, for these people, pancreas transplants can be worthwhile.

When the transplant takes, the patient no longer has diabetes and is unlikely to get it again. Insulin shots and frequent blood glucose testing are no longer necessary. Restoring normal blood glucose levels may stop complications from worsening, although many more studies are needed.

Pancreas transplants can be rejected, and roughly half of them are. Pancreases attached so that they drain into the bladder are rejected less often than pancreases attached in other body sites. When a transplant fails, the person gets diabetes again.

Remember that pancreas transplants work only for people with type 1 diabetes. The major problem in people with type 2 diabetes isn't a failing pancreas, but the body's inability to respond to insulin in the right way.

Partial pancreas transplantation

Unfortunately, there are not enough cadaver pancreases to go around because not enough people sign up to be organ donors, and each pancreas must meet strict guidelines. When a whole cadaver pancreas is not available, a person can receive a portion of a pancreas from a living relative.

When a patient with diabetes is receiving a kidney transplant from a living relative, it is usually beneficial to perform a partial pancreas transplant at the same time. Since the transplanted kidney will become damaged by diabetes over time, transplanting a partial pancreas from the same donor will help control blood glucose levels and protect the new kidney from further damage. Transplant success seems higher when patients and donors are matched for HLA types, and a pancreas transplanted along with a kidney is less likely to fail than a pancreas transplanted alone.

Benefits and risks

Pancreas transplants are safest in people who do not have heart or blood vessel disease. Before you get a transplant, your doctor will check your circulatory system to see if it is healthy enough to risk the operation.

As with any operation, the healthier you are, the better you can withstand the physical stress of surgery. Possible side effects of surgery include bleeding and infection.

Immunosuppressive drugs are hard on the body, but people who get transplants must take these drugs the rest of their lives. Azathioprine and cyclosporine, two commonly used drugs, make it more likely for you to get infections and have other side effects. You will need to avoid people who have infections, such as a cold or the flu. Also, you should not be immunized without first checking with your doctor. These drugs can also damage the kidneys. For example, using either of these medicines for many years could increase your risk for some cancers.

A recenty study (JAMA, 2003) has indicated that, for patients with functioning kidneys, survival rates of patients who receive pancreas-only transplants are worse than the survival rates of patients who manage their diabetes with conventional therapy (insulin, diet, etc.). Therefore, the decision to have a pancreas-only transplant should be very carefully considered by both the patient and physician. Because of the lower survival rates seen with pancreas-only transplants, and because a pancreas transplanted along with a kidney is less likely to fail than a pancreas transplanted alone, pancreas transplants are nearly always done only in people with type 1 diabetes who are getting or already have a transplanted kidney.