Protocol Biopsies After Pancreas Transplantation Alone?

Robert J. Stratta, MD

Disclosures

October 21, 2003

Question

What is your opinion of protocol biopsies after pancreas alone transplantation (PTA)?

Alfonso Navarro, MD

Response from Robert J. Stratta, MD

The diagnosis of pancreas allograft rejection, in the absence of a simultaneously transplanted kidney, can be problematic. Serum amylase and lipase are markers of pancreatic exocrine function, and the acinar (exocrine) pancreas typically manifests rejection prior to the endocrine pancreas. However, exocrine markers are not always reliable and reproducible in the detection of rejection. Allograft pancreatitis may occur in the absence of rejection due to infection, ischemia, reperfusion injury, or exocrine leakage. Hyperglycemia is often a late manifestation of rejection and may be associated with other causes of pancreatic dysfunction such as ischemia, drug toxicity, pancreatitis, or infection. C-peptide or insulin levels are logistically difficult to use for monitoring. Consequently, the ability to safely biopsy the pancreas allograft is a useful monitoring tool to elucidate the differential diagnosis of either exocrine or endocrine dysfunction.

It is well established that a hierarchy of rejection exists, as a PTA has a higher intrinsic incidence (and severity) of rejection than either a sequential pancreas after kidney transplant (PAKT) or simultaneous kidney-pancreas transplant (SKPT). Moreover, rejection after PTA may occur in the absence of any clinical indicators. Most studies of surveillance biopsy monitoring after PTA have shown an incidence of subclinical rejection ranging from 15% to 30%, depending on the induction and maintenance immunosuppressive regimen. For this reason, we continue to utilize surveillance biopsies after PTA and PAKT.

Since we are using thymoglobulin induction, our first surveillance biopsy is performed at 3 weeks posttransplantation. If the first biopsy is completely negative, we continue to perform biopsies every 4 weeks until the patient has 2 consecutive negative biopsies. If the biopsy shows rejection, we will treat the patient with anti-T-cell therapy (usually thymoglobulin) for 5-7 doses, increase maintenance immunosuppressive therapy, and perform a follow-up (posttreatment) biopsy at 2-3 weeks after therapy to document interval histologic improvement and then continue surveillance biopsies every 2-3 weeks until the patient has 2 consecutive negative biopsies.

If the biopsy shows minimal rejection, borderline changes, or inflammation of undetermined significance, we will treat with corticosteroids and perform a follow-up (posttreatment) biopsy at 2-3 weeks after therapy to once again document interval resolution and then continue surveillance biopsies every 2-3 weeks until the patient has 2 consecutive negative biopsies.

In the past, we would perform surveillance biopsies at 3 months, 6 months, and even 12 months after transplantation. In our experience, however, subclinical rejection is rarely detected after the first 2 surveillance biopsies, so we have simplified to the above protocol such that patients rarely are undergoing surveillance pancreas allograft biopsy more than 3 months after transplantation.

However, if the patient has evidence of either endocrine/exocrine dysfunction or unexplained fever, abdominal pain, or leukocytosis, then we have a low threshold for performing a clinically indicated biopsy to make a diagnosis or rule out rejection. We try to avoid empiric antirejection therapy in the absence of a histologic diagnosis.

With new drug regimens, the incidence of rejection of PTA is much lower, so surveillance pancreas allograft biopsies have become less important in the management of these patients. However, the ability to biopsy the pancreas allograft, whether for surveillance or clinical indications, is essential to provide optimal care to these unique patients.

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