![]() Failed Grafts ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Although excellent rates of 1-year patient and graft survival have
been achieved in recent years for all
types of technically successful pancreas transplants (SPK, PTA, PAK) a significant number of grafts are still lost in the early post-implantation period, due to a variety
of surgical complications. Graft losses
due to leaks, bleeding, thrombosis, infections and early pancreatitis are grouped together under the
category of technical failure. Currently the number of surgical complications
is disproportionately high in comparison to the number of graft loses due to
acute rejection. Thrombosis continues to be the leading cause of
non-immunological graft loss (5.8-16.4 %) with higher rates seen in PAK and PTA
cases with enteric drainage. The pancreas has intrinsically a low blood flow compared to other solid
organs. Perioperative inflammation and edema, as well as microvascular and
endothelial damage relating to donor factors and organ preservation, all
contribute to further compromise blood flow in the early post-transplant period
leading to thrombosis. Correspondingly
longer cold ischemia times have been associated with increased incidence of
graft thrombosis. Acute rejection is suspected to play a role in some patients with early
graft thrombosis. HLA mismatches appear
not to impact on the incidence of graft
loss due to technical failures, however, HLA mismatch does have an overall negative impact on graft survival. Graft pancreatectomies:
Guidelines for gross and histological evaluation Graft pancreatectomies usually consist of the whole pancreas and attached portion of duodenum. The latter is present in continuity either
with a loop of recipient's small intestine
or a patch of urinary bladder wall. Systematic histological evaluation of failed grafts is necessary for accurate
classification of the cause of graft
loss. Minimun histological sampling
should include cross sections of all large vessels and several sections from
the parenchyma to include an adequate number of medium sized and small vessels.
The number of histological
sections depends on each case; the most
important structures should be sampled routinely. Gross evaluation: - Large arteries and veins: evaluate for thrombosis (recent and
organized), endotheliitis, arteriris, transplant vasculopathy) - Random samples from parenchyma (viable and necrotic, usually 3-5
sections): evaluate for evidence of ischemia/pancreatitis, acute rejection, chronic rejection, presence
of infectious organisms, etc.). - Area of anastomosis: evaluate for dehiscences (leaks) - Samples from any other lesions: masses (i.e. PTLD), cysts, abscesses,
lymph nodes, etc.) Ancillary studies: - Immunoperoxidase
stains for insulin and glucagon should be perfomed to evaluate for selective
destruction of beta cells (recurrence of autoimmune destruction). These cases show near normal parenchyna with
no significant evidence of fibrosis/acinar loss (chronic rejection). - Frozen tissue for
immunfluorescence stains for immunoglobulins and complement in cases suspected to represent
hyperacute rejection. - Electron
microscopy: May be helpful in recurrence of diabetes type 1. Histological
evaluation: Based on the histological findings pancreatectomies can be broadly
classified as follows. 1)
PURE VASCULAR THROMBOSIS IN AN OTHERWISE NORMAL PANCREAS In these grafts the only pathological changes
consist of recent vascular thrombosis and bland ischemic parenchymal
necrosis. There is no underlying vascular pathology or any other specific
histological change. (In early
graft loss the most important histological determination relates to blood
vessels.) The majority of these grafts (78%) are lost in
less than 48 hours after transplantation and we have never seen this pattern in
grafts lost after the first 2 weeks post-transplantation. In the case of early thrombosis, the lack of obvious histological changes associated with
the thrombosis does not rule out ultrastructural
or subtle functional damage in these organs, since older donor age and longer
cold ischemia times are associated with increased risk for early
thrombosis. 2) HYPERACUTE
ALLOGRAFT REJECTION Hyperacute rejection in the pancreas is indistinguishable from hyperacute rejection affecting other organs, and it is characterized
by necrosis of arteries and veins with
secondary massive and immediate
thrombosis and parenchymal necrosis. We
have rarely seen rapid graft loss (within 1-12 hours post-transplantation) with
extensive fibrinoid necrosis of arteries and veins with associated massive
vascular thrombosis and parenchymal necrosis. Immunohistochemical studies in these cases were positive for IgG and C3 in the wall of blood vessels.
3)
ACUTE ALLOGRAFT REJECTION Graft loss secondary to acute allograft rejection
(other than hyperacute rejection) can be seen from the first week to few months
post-transplantation (in our experience
at a mean of 5.1 weeks). These cases show endotheliitis and various degrees of necrotizing arteritis (acute
rejection Grades IV-V). Graft losses
in the first months may result from a combination of infection and rejection. 4)ACUTE AND CHRONIC REJECTION Patients with with persistent (biopsy proven) acute allograft rejection can show early interstitial fibrosis
and acinar loss consistent with chronic rejection, starting in the second month
post-transplantation. In our experience graft pancreatectomies with combined
features of acute and chronic rejection
were resected at times ranging from 6 weeks to 20 months (mean 6.6 months). 5) PANCREATITIS AND
PERIPANCREATITIS Necrotizing infectious duodeno-pancreatitis with or without abscess
formation can present at variable times post-transplantation but occur often
early on (mean 3.6 months); a vaiety of
organisms can be cultured from these grafts, most commontly enterobacteria
(Enterobacter cloacae, Proteus mirabilis) and Methicillin resistant
Staphylococcus aureus (MRSA)). Fungal infections (Often Candida) and mixed
infection are not uncommon. 6) CHRONIC REJECTION These pancreatectomies show extensive interstitial fibrosis/ acinar
atrophy and transplant (obliterative) arteriopathy. This pattern can be seen after few months post-transplantation
but is more commonly seen after the second year post-transplantation (mean 28.6
months , range 4 to 81 months). Many of
these grafts do not show any significant concurrent acute rejection. Chronic rejection is the most important cause of graft loss after the
first 6 months post-transplantation. 7) POST-TRANSPLANT
LYMPHOPROLIFERATIVE DISORDER In our center allograft pancreatectomies for PTLD were performed in 4
patients in the second month post-transplantation and in one patient in month
12 (mean 5 months). The histological findings are described in the EBV section.
INCIDENCE OF
VASCULAR THROMBOSIS Recent thrombosis is seen to some degree in all cases of early graft
loss due to acute allograft rejection with vascular involvement (superimposed
on endotheliitis or arteritis) . All cases with chronic
rejection show scattered vessels with thrombosis (acute and chronic; this
typically involves medium size to small
arteries and veins. Acute vascular thrombosis in one or more large vessels can lead to
graft pancreatectomy in otherwise well
functioning allografts. In these cases the thrombosis always occurs in
abnormal blood vessels, either showing transplant arteriopathy or lesions
consistent with healing vasculitis/endotheliitis. The presence of transplant
arteriopathy (one of the histological features of chronic rejection) is
strongly associated with recent and
organized thrombosis. Correspondingly old (organized) thrombosis is seen almost
invariably in pancreatectomies with chronic rejection. As expected, progressive graft fibrosis (correlating with increasing grades of
chronic rejection) and the presence of transplant arteriopathy are directly related to the time elapsed after transplantation. Thrombosis is insignificant in the pancreatectomies performed for infectious
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cadaver donors on graft functioning recipients. Diabetes 1989;38:1-3. ![]() Please mail comments, corrections or suggestions to the TPIS administration at the UPMC.
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