Pancreas transplantation: the histologic morphology of graft loss and clinical correlations.

BACKGROUND: Graft losses due to leaks, bleeding, thrombosis, infections, and early pancreatitis are grouped together under the category of technical failure. 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 posttransplantation period shows vascular thrombosis with associated proportional parenchymal 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 been well studied. METHODS: Seventy-four consecutive pancreas graft pancreatectomies were studied histologically to evaluate for thrombosis (recent versus organized), type of vessel involved by thrombosis (arteries, veins, or both), acute rejection grade, chronic rejection grade, endotheliitis, transplant arteritis, coagulation necrosis, acute pancreatitis, presence of infectious organisms, transplant (obliterative) arteriopathy, neoplasia, relative proportions of alpha and beta islet cells, and immunoglobulin and complement deposition. The histological findings were correlated with donor and recipient data as well as clinical presentation. RESULTS: In 23 out of 39 grafts lost in the first 4 weeks posttransplantation, the only pathological changes found were vascular thrombosis and bland ischemic parenchymal necrosis. In these cases, no underlying vascular pathology or any other specific histological change was identified. Most of these grafts (78%) were lost in less than 48 hr and all in the first 2 weeks posttransplantation. Massive vascular thrombosis occurring in an otherwise histologically normal pancreas was the most common cause of graft loss in the first 4 weeks posttransplantation (59%). In most of the remaining cases (33%), although the clinical presentation suggested technical failure, there was clear histological evidence that the massive thrombosis resulted from vascular injury due to immune damage (acute and hyperacute rejection). Increased incidence of early graft thrombosis was seen in grafts from older donors and longer cold ischemia times. After the first month posttransplantation, graft pancreatectomies revealed a wider variety of pathological processes that included severe acute rejection, combined acute and chronic rejection, chronic rejection, and infections. Acute and chronic vascular thrombosis in large and small vessels was commonly seen at all times posttransplantation; chronic, organized thrombosis was strongly associated with chronic rejection. CONCLUSIONS: (a) Early acute thrombosis occurring in a histologically normal pancreas defines a true technical failure. This study showed that acute rejection leading to massive thrombosis, which clinically simulates technical failure, results in a significant proportion of early graft losses. (b) Systematic histological evaluation of failed grafts is absolutely necessary for the accurate classification of the cause of graft loss. (c) There is morphological evidence that chronically ongoing thrombosis is an important, common, contributing factor for late graft loss.     

Nuclear magnetic resonance imaging. Experience with the first 100 cases at Tygerberg Hospital

Facilities for magnetic resonance imaging (MRI) have been available in South Africa since November 1985. This article summarizes our experience with this new imaging modality, illustrates normal anatomical features and pathological conditions in sagittal, coronal and axial planes, and compares MRI with computed tomography scans of the same regions.     

Combined kidney-pancreas transplantation. Experience at the Urologic Clinic of the La Pitié Hospital]

The first attempts of pancreas transplantation were made in the middle of the 1960s and were further developed in the early 1980s with the coming of Cyclosporine. Various surgical techniques were used to carry out pancreas grafts; a total pancreatic transplantation with duodenovesical anastomosis was selected for 7 combined kidney-pancreas transplantations carried out during the past 18 months in our group. After a time lapse ranging from 18 months to 30 days, all patients were alive with functional kidney grafts. One patient only, who had lost his pancreatic graft, showed biological and histological signe of chronic rejection of his kidney graft. Five pancreas grafts are functioning, as is proved by the normal blood glucose and the normality of the markers. An immunosuppressant treatment was used in all similar cases, comprising, after an initial bolus of one gram of Methyl-Prednisolone, an initial four-drug treatment on 1/3 mg/kg/day of Prednisone, 7 mg/kg/day of Cyclosporine, 1 mg/kg/day of Imurel and, during the first fifteen days, the use of rabbit antithymocytic globulins. Ana analysis of the postoperative period revealed frequent local infectious complications, probably due to pancreatitis of the graft; however, in our experience so far, no pancreas graft was lost. The credit for this specific feature of our short series may be due to an exclusively subperitoneal approach for both the pancreas and the kidney transplantation, thus limiting the seriousness of postoperative infectious complications to a large extent.     

Rapamycin rescue therapy in patients after kidney transplantation: first clinical experience

This study was aimed at analysing rapamycin (RAPA) rescue therapy with calcineurin inhibitor (CNI) withdrawal in renal transplant patients primarily presenting with CNI-nephrotoxicity (CNI-Neph), chronic allograft nephropathy (CAN) without [CAN(a)] and with histological changes suggestive of chronic rejection [CAN(b)]. In 36 patient with CNI-Neph (n = 6), CAN(b) (n = 21), CAN(a) (n = 7), and others (n = 2) RAPA therapy was started 4.4-115 months (median 30.6 months) after renal transplantation. During a follow up of 3-33 months (median 19 months) parameters of kidney function were recorded. Three patients on haemodialysis did not show any recovery of graft function. Of the remaining 33 patients renal function improved in 22 (66.7%), was stable in three (9%) but deteriorated in eight (24%) patients, of whom seven (21%) required haemodialysis thereafter. Success rate of RAPA therapy differed with respect to the histological diagnosis: 70% in CAN(b), 80% in CNI-Neph and 33% in CAN(a). Furthermore, in patients with creatinine levels above 400 mum (n = 6) graft function rarely improved (n = 2, 33%). The RAPA rescue therapy with CNI withdrawal appears promising in a special cohort of patients with chronic renal allograft dysfunction even late after transplantation.     

Renal transplantation in patients with dense deposit disease: morphological characteristics of recurrent disease and clinical outcome.

BACKGROUND: Dense deposit disease (DDD) is an uncommon cause of end-stage renal disease (ESRD). As a consequence, information on the outcome of renal transplantation in patients with DDD comes from series with a limited number of patients. METHODS: We present the histological and clinical data of 13 adult patients with DDD, who received their first allograft in our centre in the period between 1983 and 1994. RESULTS: Renal transplant biopsies were performed in 11 patients, at 2.9 months after transplantation (median; range 0.4-13.8 months). The indication for taking the biopsy was in all instances a raised serum creatinine level. Five patients also had a significant proteinuria. In only one patient, light microscopy showed alterations in the capillary walls suggestive of a recurrence of DDD. However, by immunofluorescence or electron microscopy, we found glomerular deposits compatible with a recurrence of DDD in all 11 patients. Three patterns of glomerular C3 deposition were found: globular depositions only in the mesangium; mesangial accumulation with linear deposits in the capillary wall; and prominent linear presence in the capillary wall with only a few mesangial granules. The findings by electron microscopy matched the immunofluorescence results. The linear C3 accumulation in the capillary wall was visible ultrastructurally as electron-dense ribbon-like transformation of the glomerular basement membrane. Mesangial C3 deposits were seen ultrastructurally as local electron-dense deposits in the mesangium. Four patients showed a pronounced glomerular influx of neutrophils, accompanied by crescents in three patients. In these three latter patients, the recurrence of DDD was the only histological lesion. In the other patients, the recurrence was merely a coincidence, the biopsy demonstrating an additional histological lesion (three chronic vascular rejection, two acute rejection, one ischaemic necrosis and two cyclosporin A toxicity). Eight patients with a recurrence of DDD have progressed to ESRD at an average of 14 months (range 0.2-38 months) after transplantation. The recurrence was the sole cause of graft loss in the three patients with crescents. The patients in whom the C3 deposits were confined to the mesangium appeared to have a better prognosis. CONCLUSIONS: The histological recurrence rate of DDD is high. The histological picture is quite diverse, and in most patients abnormalities are only found by immunofluorescence and electron microscopy. Up to one-quarter of the patients with DDD lost their grafts because of a recurrence.     

Experience with cyclosporine and steroids in clinical renal transplantation.

We have reviewed the results of patient survival and transplant function of the last 100 recipients of renal allografts treated with cyclosporine (CyA) plus low-dose steroids since November 1981; the follow-up varies between 3 months and 2 years. A group of 56 individuals transplanted between January 1980 and October 1982 and immunosuppressed with azathioprine (Aza) and steroids were used as comparison. There were five deaths among 100 patients treated with CyA and two among 56 treated with Aza. There were, however, marked differences in allograft function. Using actuarial curves, 2-year allograft survival from 24 living, related, one haplotype matched donors was 83%, as compared to an unsatisfactory 60% graft function among 24 nonrandomized, comparable, Aza-treated recipients. The 2-year actuarial survival of 76 allografts from cadaver donors was 76%; that of 36 grafts in patients treated with Aza, 48%. Interestingly, function of first cadaver allografts was 84% at 2 years, far better (p less than 0.002) than cadaver graft function (58%) in patients who had been previously transplanted; these latter results are comparable to Aza-treated cadaver recipients. Side effects and complications of this difficult drug, as well as its benefits, have been stressed in this article.     

Laparoscopic cholecystectomy. Experience of the first 150 patients.

Between April 1991 and May 1992, 150 patients were treated by laparoscopic cholecystectomy. Eleven patients (7.3%) required conversion to open laparotomy and five (3.3%) patients were operated on for postoperative complications. There were two (1.3%) patients with a hepatic duct lesion, one of which was treated with a T-tube alone but the other required a bilioenteral reconstruction. The average operation time was 72 minutes (range 30-240 minutes). The mean hospital stay of all patients was 2.1 days (range 1-28 days) and the mean time to return to work was 11.5 days (range 6-60 days).