Should We Be Performing Pancreas Transplants?

The vast majority of the 1 million people with Type I dia- betes in the United States are treated with maintenance exogenous insulin therapy. Only about 1 in 1000 (approx- imately 1300/year) are treated with transplantation. The whole organ pancreas transplant has been one of the most difficult organs to transplant successfully because of a high risk for pancreatitis, graft thrombosis and rejection. A decade ago, one could question the wisdom of perform- ing a pancreas transplant in any patient. However, with improvements in immunosuppression and patient man- agement, the field has improved steadily. Simultaneous pancreas kidney (SPK) transplantation was the first to show an improvement and now several reports have suggested that SPK leads to increased patient survival and a better quality of life compared to a kidney transplant alone. In soli- tary pancreas transplantation, either pancreas after kidney (PAK) or pancreas transplant alone (PTA), a survival bene- fit has been more difficult to ascertain. In fact, Ventstrom et al. actually reported a survival disadvantage for PAK in their paper published in the Journal of the American Medi- cal Association (1). In the present issue of AJT , Gruessner et al. revisit the question of the survival benefit of PAK, with their data indicating, that with the current cohort of patients and current follow-up, neither a survival advantage nor disadvantage could be found. The survival benefits of transplantation are most often as- sessed retrospectively, as prospective studies are often not feasible because of ethical concerns (e.g. if a proce- dure is perceived to be vastly superior), but also because of financial, patient resource and statistical power con- straints. Even the most sophisticated retrospective com- parisons are plagued by important selection biases that of- ten times are not readily recognizable by the clean numbers presented in analysis tables. An obvious bias in assessing a survival advantage of transplantation lies in the fact that the selection process is geared to direct organs toward those patients who are healthy enough to safely undergo transplantation, which leaves sicker patients in the non- transplanted group. A partial but far from perfect solution to this bias is to use as the comparison group, patients that have been cleared for and are awaiting transplantation. It is unclear though, how to most appropriately handle this comparison group. For example, the decision of whether or not to censor patients who go off the waiting list does not make the reference group more or less appropriate, but it clearly changes the mortality risk of the comparison group and perhaps the result of the analysis. There is really no ideal way of handling all the potential biases, and both the Venstrom and Gruessner paper have their own underlying biases in how they handle the reference group.