Pancreas transplantation: The histologic morphology of graft loss and clinical correlations

Background. Graft losses due to leaks, bleeding, thrombosis, infections, an d early pancreatitis are grouped together under the category of technical f ailure. Among these complications, massive vascular thrombosis continues to be the most important cause of early graft loss due to technical failure. Pathological evaluation of most allografts lost early in the posttransplant ation period shows vascular thrombosis with associated proportional parench ymal necrosis, The morphological findings in allografts that are considered to be lost due to technical failure has not been systematically addressed. In particular, the role of acute rejection in early graft loss has not bee n well studied. Methods. Seventy-four consecutive pancreas graft pancreatectomies were stud ied histologically to evaluate for thrombosis (recent versus organized), ty pe of vessel involved by thrombosis (arteries, veins, or both), acute rejec tion grade, chronic rejection grade, endotheliitis, transplant arteritis, c oagulation necrosis, acute pancreatitis, presence of infectious organisms, transplant (obliterative) arteriopathy, neoplasia, relative proportions of alpha and beta islet cells, and immunoglobulin and complement deposition. T he histological findings were correlated with donor and recipient data as w ell as clinical presentation. Results. In 23 out of 39 grafts lost in the first 4 weeks posttransplantati on, the only pathological changes found were vascular thrombosis and bland ischemic parenchymal necrosis. In these cases, no underlying vascular patho logy or any other specific histological change was identified. Most of thes e grafts (78%) were lost in less than 48 hr and all in the first 2 weeks po sttransplantation. Massive vascular thrombosis occurring in an otherwise hi stologically normal pancreas was the most common cause of graft loss in the first 4 weeks posttransplantation (59%). In most of the remaining cases (3 3%), although the clinical presentation suggested technical failure, there was clear histological evidence that the massive thrombosis resulted from v ascular injury due to immune damage (acute and hyperacute rejection). Incre ased incidence of early graft thrombosis was seen in grafts from older dono rs and longer cold ischemia times, After the first month posttransplantatio n, graft pancreatectomies revealed a wider variety of pathological processe s that included severe acute rejection, combined acute and chronic rejectio n, chronic rejection, and infections. Acute and chronic vascular thrombosis in large and small vessels was commonly seen at all times posttransplantat ion; chronic, organized thrombosis was strongly associated with chronic rej ection. Conclusions. (a) Early acute thrombosis occurring in a histologically norma l pancreas defines a true technical failure. This study showed that acute r ejection leading to massive thrombosis, which clinically simulates technica l failure, results in a significant proportion of early graft losses. (b) S ystematic histological evaluation of failed grafts is absolutely necessary for the accurate classification of the cause of graft loss. (c) There is mo rphological evidence that chronically ongoing thrombosis is an important, c ommon, contributing factor for late graft loss.