Pancreas Transplantation - pediagenosis
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Saturday, November 2, 2019

Pancreas Transplantation


Pancreas Transplantation
Categories of transplant
Simultaneous pancreas and kidney (SPK, 80%)
The pancreas is transplanted at the same time as a kidney from the same deceased donor. The recipient is in kidney failure, and either on or within a few months of starting dialysis. This combination is a bigger surgical operation, but has the benefit that the kidney can be used as a surrogate to monitor rejection of both grafts.

Pancreas after kidney transplantation (PAK, 15%)
Where patients have previously undergone a kidney transplant, e.g. from a live donor, or an SPK where the pancreas has failed, a subsequent solitary pancreas can be performed. This may affect the residual renal function, which needs to be carefully assessed.

Pancreas Transplantation

Pancreas transplant alone (PTA, 5%)
Indicated for life-threatening hypoglycaemic unawareness.
Patient assessment
Pancreas transplantation is a major surgical operation with a higher than average risk of complications that might necessitate further surgery. Candidates for the procedure are carefully assessed with this in mind.
The basic clinical assessment of a potential pancreas recipient is similar to that of a potential kidney transplant recipient. Particular note is taken of active ulceration or sepsis, which is a contraindication to transplantation. Examination should assess the degree of neuropathy, in addition to a full cardiovascular, respiratory and abdominal examination.
A thorough cardiovascular assessment is essential, and comprises ECG and echocardiography, with stress imaging (dob-utamine stress echo or radionuclide scan); coronary angiography, carotid duplex scanning and abdominal duplex or CT are frequently required. In addition, screening for gallstones is worth- while since cholecystectomy at the time of transplant may avoid cholecystitis in the post-operative period.

Transplantation
The donor organ
The pancreas is transplanted as a bloc of tissue, which also includes the donor duodenum. The pancreatic arterial supply comes from the splenic artery and inferior pancreaticoduodenal branch of the superior mesenteric artery; these two arteries are joined together on the back table before surgery utilising the donor’s common iliac artery bifurcation as a conduit, giving just one arterial anastomosis in the recipient. The venous drainage is via a 1 cm stump of donor portal vein.

Exocrine drainage
The pancreas produces around 1.5 litres of enzyme-rich secretions each day. This must be drained either by anastomosing the donor duodenum to the dome of the bladder (bladder drainage) or to a segment or Roux-en-Y loop of small bowel (enteric drainage). Bladder drainage has the advantage that the urinary amylase concentration will give an indication of the function of the graft; it has the disadvantage of massive bicarbonate loss and may cause a chemical cystitis necessitating subsequent conversion to enteric drainage. Most centres now perform primary enteric drainage, although bladder drainage may be preferred for solitary transplants where the ability to monitor the urinary amylase may be more important.

Venous drainage
The venous drainage may either be fashioned by anastomosing the donor portal vein to the inferior vena cava (IVC) or one of its tributaries, or to the superior mesenteric vein (SMV). The IVC has the advantage of being simple; the SMV is more physiological, because insulin is delivered to the portal circulation.
Systemic venous drainage (i.e. to the IVC) results in higher systemic insulin levels and a delayed response to increasing glucose and decreasing glucose, the latter accounting for hypoglycaemic episodes that these patients sometimes experience.
The pancreas is usually placed intraperitoneal through a midline incision, although extraperitoneal placement like a kidney is possible so long as a window into the peritoneum is made to facilitate drainage of the inflammatory exudate that arises following transplantation.

Immunosuppression and prophylaxis Lymphocyte-depleting monoclonal antibodies such as alemtuzumab are used to permit steroid-free immunosuppression; tacrolimus and mycophenolate are the usual maintenance agents. Care should be taken with sirolimus because its ability to delay healing may have catastrophic consequences should foot ulceration occur.
In addition to the usual prophylaxis given for kidney transplantation, prophylactic antifungal (e.g. fluconazole) and broad-spectrum antimicrobial (e.g. meropenem) agents are given because the duodenal contents may be contaminated.

Complications
Surgical complications
Thrombosis occurs in 5–10% of pancreas transplants. There are several reasons.
·      The splenic and superior mesenteric arteries and portal vein are large vessels capable of handling flows of 1.5 L/min; in isolation the pancreas has a blood supply nearer 100 ml/min so there is significant stasis in the vessels.
·      Pancreatitis occurs secondary to ischaemic damage. This also predisposes to thrombosis.
·      Diabetes is often associated with a hypercoagulable state.
Bleeding. The mesenteric vessels pass through the neck of the pancreas and are oversewn along the cut edge of the mesentry; the vessels to the spleen and inferior mesenteric vein (IMV) are also ligated. Nevertheless, bleeding on reperfusion and post-operatively is common, and frequently requires a second laparotomy. The necessity to give antithrombotic prophylaxis increases the risk of bleeding.
Intra-abdominal hypertension requiring interposition mesh closure of the abdominal wall may result from the extra volume of tissue transplanted into often small abdomens.

General complications
As with any abdominal surgery there is a risk of chest infection, wound infection and wound breakdown. Patients are also at risk of the long-and short-term complications of immunosuppression.
Foot ulceration, particularly heel ulceration following pro-longed immobilisation, is a risk so patients are nursed on an air mattress to minimise pressure.
Metabolic complications include bicarbonate loss from a bladder-drained pancreas and hypoglycaemia from a systemic venousdrained pancreas.

Long-term outcomes
Patients are generally insulin independent from the time of transplantation. The 1-year graft and patient survival are 90% and 98%; thereafter the half-life of a pancreas transplant is around 10 years if transplanted with a kidney, and less if transplanted in isolation  (PAK,  PTA).  Pancreas  transplantation  has  a  higher 1-year mortality than kidney transplantation alone, but a far superior 10-year survival due largely to beneficial effects in reducing cardiac events.

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