Overview of Pancreas Transplantation
The first successful pancreas transplant was performed by WD Kelly in 1966. Since then, the outcomes of pancreas transplants have significantly improved. These improvements can be attributed to advancements in surgical techniques and more effective medications to suppress the immune system. Over the last three decades, these advancements have made the process of pancreas transplantation much more successful. Particularly for patients with type 1 diabetes, a pancreas transplant is the closest thing we have to a cure.
In 1984, the International Pancreas Transplant Registry was created. This registry has collected data from over 48,000 pancreas transplants that have been performed in the past 30 years. It’s important to note that diabetes mellitus is a leading cause of end-stage kidney disease worldwide.
When kidneys fail (a condition known as end-stage renal disease), a kidney transplant is usually the best treatment. However, for diabetes patients, a kidney transplant alone might not be enough. This is because metabolic abnormalities caused by diabetes can continue to occur, or even get worse, even after a successful kidney transplant. A pancreas transplant is the only known treatment that can maintain normal blood sugar levels and bring glycosylated hemoglobin levels back to normal in patients with type 1 diabetes. Glycosylated hemoglobin is a measure of blood sugar control over the last two to three months.
It’s also notable that the success rate for combined kidney and pancreas transplants is similar to the success rates for kidney, liver, and heart transplants alone. This means that at one year and five years after surgery, rates of survival and organ function are comparable across these different transplant procedures.
Anatomy and Physiology of Pancreas Transplantation
The pancreas is an organ that is crucial for our body’s digestion process and how it uses and stores energy. This organ has two main parts: the exocrine and endocrine pancreas. They have different roles but work in harmony. Signals from the nervous system and hormones regulate both parts of the pancreas. The exocrine part helps us digest our food, while the endocrine part helps keep our blood sugar levels steady by regulating glucose.
Speaking of the endocrine part, even though it makes up just 2% of the pancreas, it’s pretty vital. Within this part, there are different groups of cells known as islets of Langerhans. These cells include insulin-producing beta-cells (making up 65% to 80% of the total), glucagon releasing alpha-cells (about 15% to 20%), somatostatin producing delta-cells (around 3% to 10%), pancreatic polypeptide-containing PP cells (1%), and ghrelin containing epsilon-cells (less than 1%).
The other part, called the exocrine pancreas, consists of acinar and ductal cells. These cells collectively produce and transport enzymes needed for digestion into a part of the small intestine called the duodenum.
The pancreas, all in all, is a singular organ that is about 14 to 18 cm long, 2 to 9 cm wide and 2 to 3 cm thick, weighing somewhere in the range of 50 to 100 grams. It can essentially be divided into three parts: the head, body, and tail, without any clear borders between them. Some experts might also refer to a fourth and fifth part, which are considered part of the head of the pancreas.
The head of the pancreas is shaped like a “C” along with the upper bend of the duodenum. This part of the pancreas is found behind the stomach, and it stretches almost horizontally inside your body. The tail of the pancreas is located near the spleen. This whole organ is surrounded by a fibrous capsule, which further creates tissue sections, splitting the inside into lobes and lobules. About 15% to 25% of the pancreas is made up of tissue called mesenchymal tissue, which includes numerous fat cells.
Why do People Need Pancreas Transplantation
There are four different ways to transplant a pancreas:
1. Pancreas transplant alone, also known as a PTA.
2. Simultaneous pancreas and kidney transplant, or SPK.
3. Pancreas after kidney transplant, which is known as PAK.
4. Transplant from a deceased donor’s pancreas and a live donor’s kidney at the same time.12
A pancreas transplant alone might be the best option for people with severe complications from diabetes. This is a condition where the body cannot control sugar levels in the blood. Some of these patients experience severe drops in blood sugar levels, or they might have a life-threatening condition called ketoacidosis, which is an excessive level of acids in the blood. These patients find that insulin therapy no longer helps them and their quality of life is degrading. Their kidneys are functioning well and they have no buildup of waste products in their blood – a condition called uremia. Their kidneys are likely to continue working well because their filtration rate – the rate at which the kidney filters the blood – falls into the healthy range of 80 to 100 mL/min/1.73 m2.12
An SPK transplant becomes a choice for patients with type 1 diabetes who also have end-stage renal failure – this means their kidneys have stopped working and they are on dialysis, a treatment that performs the job of kidneys, or will need dialysis soon. For these patients, the pancreas and kidney come from the same deceased donor.
After a kidney transplant, some patients will need a pancreas transplant. This is done in patients who meet the criteria for a pancreas-alone transplant and those whose kidney transplants are functioning well. This approach helps to reduce the waiting time and mortality rate compared to an SPK transplant.
Interestingly, one benefit of getting a pancreas from a deceased donor and a kidney from a live donor together is a lower rate of the new organ not functioning immediately – this is known as delayed graft function. This approach also significantly shortens the waiting times and improves the survival rate compared to patients awaiting an SPK transplant.12
Currently, SPK is the best option for patients with type 1 diabetes and related end-stage renal disease. Pancreas-alone transplants are performed in patients whose kidney functions are normal but they do not notice when their blood glucose levels become dangerously low (hypoglycemic unawareness).13
The benefits of pancreas transplants include better control of blood glucose levels and an improved quality of life. On the other hand, kidney transplant in diabetic patients doesn’t work well and the prognosis is usually poor. Pancreas transplants, both SPK and PAK, are performed for people with insulin-dependent diabetes (either type 1 or type 2) who have chronic kidney failure.7
Despite the recent decrease in pancreas transplants, the outcomes have improved noticeably for all types of transplants due to advancements in immunosuppression (medicines that lower the body’s ability to reject a transplanted organ), improved surgical technique, and a better selection of donors and recipients. The drop in pancreas transplants can be due to improved insulin delivery systems, concerns about the outcomes after solitary pancreas transplants, and a new interest in islet transplants (a procedure where cells from a healthy pancreas are transplanted to a patient). However, pancreas transplants are only an option for a selected group of diabetic patients who have chronic kidney failure, complications affecting other parts of the body than the kidney, or struggle with difficult control of blood glucose levels.16
When a Person Should Avoid Pancreas Transplantation
There are some conditions that make a pancreas transplant absolutely impossible. These include:
Being over 65 years old. Having heart disease that can’t be corrected with treatments, which is a major risk for the procedure. Suffering from a heart attack within the past six months. Having a heart that isn’t pumping blood well (known as “left ventricular ejection fraction” under 30%) or having high blood pressure in the lungs (over 50mm Hg).
Other conditions that rule out a transplant include incurable cancer (except for skin cancer that hasn’t spread, or a low-grade form of prostate cancer), a severe infection throughout the body, stomach ulcers, a weakened immune system, severe mental health issues that might stop a person from following their treatment correctly, or any other reason that could make surgery too dangerous.
There are also “relative contraindications” – these are conditions that might not necessarily rule out a transplant, but that will make it riskier or more complicated. They include:
Having a stroke that causes long-term damage, having an active infection of hepatitis B or C virus, being overweight (a body mass index over 30 kg/m), requiring a high amount of insulin (over 1.5 units/kg per day), having severe disease of the blood vessels in the lower body, or abusing alcohol, tobacco, or drugs.
Preparing for Pancreas Transplantation
When it comes to pancreas transplants, the selection of donors is pretty strict. This can sometimes limit the number of potential donors. If a donor has a history of heavy drinking, diabetes in the family, or high levels of a digestive enzyme called serum amylase in their blood, their pancreas may not make the cut. Also, doctors typically don’t use pancreases with scarring or fat build-up because these can cause severe inflammation once reconnected in the recipient. This can result in serious health problems or even death. Pancreases from overweight donors or those older than 60 are also usually declined, as the pancreas is delicate and can get injured during removal.
When picking a donor, doctors aim to match the prospective recipient as closely as possible with the ‘ideal’ donor. To do this, they maintain the potential donor’s body extremely well to avoid any unstable blood pressure or heart rate conditions. The donor’s blood type should match the recipient’s, and they should typically be between 5 and 50 years old. If only the pancreas is being donated, the donor should weigh between 30 and 50kg, and more than 50kg if both the pancreas and liver are being donated. Doctors also consider any signs of pancreatitis, swelling of the gland, internal bleeding, fat build-up or hardened texture in a pancreas as these can increase the risk for complications after the transplant. Donors can get excluded if they have type 1 diabetes, pancreatic disease, if they’ve had certain previous surgeries, cancer, certain infectious diseases, chronic liver disease, a body mass index above 40 kg/m2, or a history of chronic alcohol abuse.
Due to the shortage and high demand of transplant organs, the criteria for donors are sometimes stretched to include more high-risk groups, but this can result in higher chances of transplant failure. To identify suitable donors, transplant teams use the P-PASS score (a score calculated on 9 health parameters of the donor) and the pDRI system(a measurement to predict outcomes after a pancreas transplants). Donors with a P-PASS score less than 17 are considered for transplants as they have three times the average acceptance rate.
The waiting list for pancreas transplants has been growing over the years in many countries. Since 2000, the number of patients waiting for a transplant has steadily increased. Only 1,005 patients were added to the active candidates list in 2011. Despite this, recent information is showing that these waiting lists are still expanding all over the world.
How is Pancreas Transplantation performed
A pancreas and a kidney transplant can be done at the same time or one after another. If only the pancreas is being transplanted, the procedure can take about 3 to 4 hours. But, if both the pancreas and kidney are being transplanted together, it may stretch to about 6 to 8 hours. In general, the kidney is placed on the left side of your belly, and the pancreas is placed on the right side. Notably, the original or “native” pancreas and kidneys are not taken out.
The blood vessels of the new pancreas are connected to the iliac vessels, this is the main group of blood vessels in the lower part of your belly. Since the pancreas has two primary blood supply routes, a ‘Y’ graft is made using blood vessels from the donor; this allows the pancreas to be supplied by a single blood vessel. A connection is also made between the small intestine and the pancreas so that the digestive juices produced by the pancreas can get drained into the intestine. A segment of the duodenum (the initial part of the small intestine) from the donor is used to make this connection. All these steps are carried out through one or two cuts in your belly or groin area.
If the pancreas is being taken from a donor who is also donating several other organs, the pancreas is removed using a certain technique after the liver has been taken out. This essentially involves taking out the pancreas together with the duodenum and spleen, and few blood vessels from the area are preserved as well. The donor’s spleen is then removed from the pancreas-duodenum combination. Then, a ‘Y’ graft is created between the pancreas-duodenum combination and the blood vessels. This is typically done through a cut along the center of your belly.
Monitoring the health of the new pancreas can be a bit tough because there aren’t simple ways to tell early on if there’s any injury to the transplanted pancreas. Thus, high blood sugar or hyperglycemia (which is a pretty late sign of significant and irreversible damage to the pancreas), an increase in serum amylase and lipase levels (certain enzymes produced by the pancreas), and basal and stimulated C-peptide levels (which is a measure of how well the transplanted pancreas is functioning) are usually monitored. With some techniques, doctors can measure the pancreas’s function by measuring a substance called amylase in your urine or by examining tissue from the duodenum.
Similar to other solid organ transplants, pancreas transplant patients require immunosuppression, or medication that reduces the body’s immune response to prevent it from rejecting the new organ. These medications can include thymoglobulin, alemtuzumab, or basiliximab, followed by tacrolimus and mycophenolate, as well as possibly steroids. In addition, to avoid blood clots in the new pancreas graft, patients are given a low dose of a type of anticoagulant twice daily.
Possible Complications of Pancreas Transplantation
Getting a pancreas transplant can be a complex operation and it’s not without its risks. There can be quite a lot of complications after the surgery that can sometimes require more surgery. Some of these complications could include heavy bleeding, infection (known as sepsis), inflammation of the pancreas (pancreatitis), and blood clots (thrombosis). However, the risks linked to blood clots have been improved recently through better monitoring of blood thickness (coagulation).
One of the problematic complications is the injury caused by the lack of blood supply followed by sudden normalization of blood supply (ischemia-reperfusion injury). In simple terms, this means damage happens when the blood supply returns to the tissue after a period of lack of oxygen. In such cases, this problem may result in inflammation of the pancreas and infection, leading in some instances to a fluid leakage from the pancreas.
During any surgical procedure, there’s always a chance that you could bleed, and this comes with an approximated risk of 5%. Blood clots can also cause the new pancreas to stop working, though there are anticoagulant medications (like heparin, citrate, or epoprostenol) that can be used to reduce this risk. There are some other complications to note as well such as leaks at the surgical site where the pancreas connects with the intestines(gastrointestinal anastomotic leak), pancreatitis, infection within the abdominal cavity (intra-abdominal sepsis), and heart conditions.
It’s important to note that the new pancreas also has an underlying risk of being rejected by your body, this occurs between 5 to 25% of the time depending upon the type of treatment used to suppress the immune system. A quick diagnosis of rejection can improve outcomes, but this can often be challenging. This is why doctors will typically monitor things like your blood sugar levels, try to measure the amount of insulin being produced by the pancreas, check the levels of a substance called C-peptide and other similar parameters to diagnose the rejection process.
Medical imaging techniques like ultrasound, CT scans, and MRI are essential for observing possible blood clots in the new pancreas. Blood clots can either be partial or complete. Complete clots can lead to a loss of the new pancreas unless urgent procedures are done to remove the clot, while partial clots can usually be treated with anticoagulants.
After the operation, you might experience a range of complications including pancreatitis, the accumulation of fluid around the pancreas (peripancreatic fluid collections), leaks from the pancreas, blood clots, and heavy bleeding. In some cases, there could present complications related to the surgical suture of the duodenum with the recipient’s intestine (duodenal graft complications (DGC)), which is seen in about 20% of patients who get a pancreas transplant.
Technical failure, or the loss of the graft within the first three months due to blood clots, pancreatitis, infections, fistulas (abnormal connection between two body parts), and bleeds could also cause the loss of the newly transplanted pancreas.
Depending on the method of how your new pancreas was put in, there can be specific complications too. If your new pancreas was attached to your bladder (vesical drainage), you could face urinary and metabolic problems. In some cases, people might need further surgery to connect the new pancreas to the intestine instead. Those who receive a pancreas with this bladder attachment can also experience metabolic acidosis (excess acid in the body due to the loss of bicarbonate in urine) and dehydration, requiring careful control of fluid and bicarbonate levels.
When the new pancreas is connected to the intestine, this poses a risk of leaks from the intestine which poses a risk to the patient’s survival. Factors that increase the risk of these leaks include prolonged lack of blood supply to the pancreas followed by re-supply, trauma to the duodenum, pancreatitis after blood supply is restored, and infection within the abdomen. Removal of the pancreatic graft is usually the treatment for this sort of complication.
Infections are a serious cause of complications and deaths in pancreas transplantation. The most common are bacterial infections, particularly affecting the abdominal wall and urinary tract. Virus infections, particularly cytomegalovirus are also possible due to the immune-suppressing treatment given. On top of this, there is also the risk for fungal infections, so it’s important to diagnose these early on for successful treatment.
So, while there are numerous potential complications linked with pancreas transplantation, the procedure has seen significant improvement over the years in both surgical technique and post-operative care. These advances ensure the possible complications are closely monitored and treated promptly for most of the patients undergoing the procedure.
What Else Should I Know About Pancreas Transplantation?
After a transplant procedure, patient survival rates are excellent: more than 96% of patients live after one year, and more than 83% live up to five years. The longest a transplant has been known to last are 26 years for combined kidney and pancreas transplants, 24 years for a pancreas transplant after a kidney transplant, and 23 years for a pancreas transplant alone.
For people with diabetes, a pancreas transplant can help control blood sugar levels. According to the Diabetes Control and Complications Trial, it lowers the HbA (hemoglobin A1c, a blood test that measures average blood sugar levels over the past three months) to normal levels, even after ten years. This means that blood sugar levels are 42 mmol/L on average after 6 years, compared to 55 mmol/L for patients treated with intense insulin therapy. Some studies also suggest that a pancreas transplant can improve the body’s fat metabolism.
Pancreas transplantation is the only available treatment that can restore long-term normal blood sugar levels without the risks of low blood sugar (hypoglycemia). In addition, pancreas transplants can dramatically improve diabetic kidney disease (glomerular lesions) after ten years.
People living with diabetes and advanced kidney disease (end-stage renal disease) face significant health risks and shortened lifespan. A combined kidney-pancreas transplant (SPK transplant) can vastly improve the quality of life and life expectancy for these patients.
After two years of a successful transplant, diabetic patients also see improvements in their nervous system function. Pancreas transplantation not only enhances heart health and reduces diabetes-related kidney disease in type 1 diabetic patients but it also enhances their quality of life. Neuropathy (nerve damage), retinopathy (eye damage), and the healing of certain skin lesions can all improve after a pancreas transplant.
