Biomedical subjects
Publications and source records attributed to S G Pollard.
A modified caval preservation technique with the potential for decreased incidence of venous outflow obstruction and haemorrhage.
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The urological complications of renal transplantation are well documented. In 1990, our experience of 507 consecutive renal transplants using the Leadbetter-Politano technique, which was unsplinted in the vast majority of patients, had a ureteric complication rate of 7.7%. Here, we report the long-term incidence and management of our ureteric complications in 1186 consecutive renal transplants done over the following 11 years using an extravesical onlay stented ureteroneocystostomy. We report a considerable reduction in the urological complications of renal transplantation to 3.8%. Furthermore, we were able to use percutaneous radiological techniques to salvage the majority (84.7%) of ureteric complications. Recourse to surgery was required rarely but enabled salvage of all treatment failures.
BACKGROUND: In recent years, several reports from North America have highlighted the success of conservative treatment in patients with blunt liver trauma. The aim of this study was to identify trends in the management of blunt liver trauma in a UK tertiary referral centre dealing with both adults and children over a 10-year period. METHODS: A retrospective case note review was performed on 71 consecutive patients (58 male patients) of median age 25 years admitted to the hepatobiliary unit over the 10-year period from 1992 to 2001 with blunt liver trauma. Data relating to referring source, severity of liver injury, initial and subsequent management and outcome were collected using a standard pro forma. RESULTS: Sixty-two of the 71 patients were referred from other surgical units. Of these, 14 had undergone laparotomy at the referring hospital, with ten having perihepatic packing; the other 48 were managed conservatively. Of the 62 patients transferred to the authors' unit, 12 required surgical intervention for the liver injury. The mean number of patients with blunt liver trauma increased between the first second 5-year periods, from 3.2 to 11.0 patients per year. There was a significant reduction in the proportion of patients requiring surgery for the liver injury in both the authors' unit (from seven of 16 patients in 1992-1996 to seven of 55 in 1997-2001; P = 0.017, chi(2) test) and referring hospitals (from six of 12 to eight of 50; P = 0.014, chi(2) test). The reduction in the mortality rate, from two (12.5 per cent) of 16 in the first period to four (7.3 per cent) of 55 in the second, was not significant (P = 0.880, chi(2) test). CONCLUSION: This study demonstrated a marked increase in the number of patients with blunt liver trauma referred to a regional hepatobiliary centre in recent years. It has confirmed that the majority of such patients can be treated successfully without surgery.
Cyclosporine was introduced into clinical transplantation as an immunosuppressive agent 20 years ago. Cyclosporine is a critical dose drug with a narrow therapeutic index and requires monitoring through blood levels to avoid rejection through underexposure or toxicity through overexposure. Traditional monitoring was by measuring the trough level taken 12 hours after an oral dose, but the results correlated poorly with drug dose, toxicity, and outcome. Monitoring cyclosporine by calculating total drug exposure correlated better with outcome but was time consuming and labour intensive. An abbreviated measure of exposure over the first 4 hours after administration was found to predict outcome and allow dose adjustment. This was based on the observation that the majority of variability in the absorption of the drug was during the first 4 hours after administration--the absorption phase--and this was not reflected in the trough level. Cyclosporine exerts its immunosuppressive action by inhibition of calcineurin. The peak of this inhibition occurs during the peak concentration of the drug, which occurs during the absorption phase. On the basis of the fact that as a single time point the 2-hour level was the best surrogate marker of the maximum level, a strategy for monitoring by 2-hour levels (C2) evolved. It was shown in all organ types to be the best single point predictor of exposure and has led to an improvement in outcome both in de novo and in maintenance transplant patients.
Living donor liver transplantation (LDLT) has the capacity to reduce the current discrepancy between the number of patients on the transplant waiting list and the number of available organ donors. For pediatric patients, LDLT has clearly reduced the number of waiting list deaths, providing compelling evidence for an increase in LDLT programs. This review discusses many of the recent advances in LDLT.
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BACKGROUND: A prospective, open-label, study was conducted at 29 centers in 9 countries, involving 307 de novo liver transplant patients to compare the clinical usefulness of monitoring 2-hr post-dose cyclosporine (CsA) levels (C2) with conventional trough cyclosporine blood levels (pre-dose) (C0). METHODS: Neoral oral therapy was initiated at 15 mg/kg/day and dose adjusted according to predetermined C2 or C0 target level ranges. The primary efficacy variable was treatment failure at 3 months, where evaluation was based on a composite endpoint of biopsy-proven rejection, treatment for rejection, graft loss, death, or premature withdrawal/discontinuation from the study. RESULTS: Baseline characteristics were similar between groups. Graft loss at 12 weeks (retransplantation or death) occurred in 6.8% C2 and in 7.0% C0 patients. Overall incidence of treated acute rejection was lower for C2 (23.6%) than C0 patients (31.6%) (P=0.144, Cochran-Mantel-Haenszel [CMH] test). In hepatitis C virus (HCV)-negative patients, the incidence of rejection in the C2 group was significantly less than in the C0 group (21.2% vs. 33.0%; P<0.05), whereas in HCV-positive patients, the rejection rate was similar in both groups (26.7% for C2 group vs. 27.3% for C0 group: P=0.81). C2 patients (n=16) who reached minimum target CsA levels by day 3 had a notably low incidence of rejection (12.5%), whereas there was no difference in the incidence of rejection in C0 patients, irrespective of time to reach target level. For biopsy-proven acute rejections (21.6% for C2 vs. 30.4% for C0), the incidence of moderate and severe histological diagnosis was significantly lower in the C2 group than in the C0 group (47% vs. 73%; P=0.01). Safety profiles were similar between the two groups, with few patient withdrawals due to adverse events (9.5% for C2; 7.0% for C0). CONCLUSIONS: Using C2 monitoring, the overall incidence of acute cellular rejection was lower compared with the C0 group, and the histological severity of acute rejections was shown to be significantly milder for the C2 group, indicative of good long-term prognosis. These data demonstrate that the use of C2 monitoring is superior to C0 and results in a reduction in the incidence and severity of acute cellular rejection without detrimental effect on the drug safety profile.
The development of small bowel transplantation has long been hindered by the immunological and infectious barriers peculiar to the small bowel. Gradual progress has been achieved during the past decade with the use of tacrolimus and the availability of better anti-infection prophylaxis. The current status of small bowel transplantation as a life-saving option for patients failing on total parenteral nutrition and those who have developed irreversible liver failure is undisputed. Small bowel transplantation can be performed as either an intestine-only graft or as part of a composite graft with the liver and, on occasion, other organs. The various techniques of donor and recipient operations are relatively standardized. Despite the progress made, the most common causes of death and graft loss continue to be sepsis, rejection, and lymphomas. Further progress can be achieved by development of more effective immunosuppressive and immunomodulatory strategies. The role of inducing chimerism by adjuvant donor-specific bone marrow transfusions to promote graft tolerance is uncertain. Until the mortality and graft losses are further reduced, the role of small bowel transplantation will be limited to a salvage procedure for failure of total parenteral nutrition rather than a primary treatment of intestinal failure.
OBJECTIVE: Laser Doppler flowmetry (LDF) has been used as a research tool to measure splanchnic perfusion. In this report, we aim to demonstrate the clinical value of this technique in perioperative monitoring of transplanted small bowel. METHODS: A 24 year old man underwent small bowel transplantation using a previously described technique. Microvascular blood flow in the transplanted bowel was measured using an LDF splanchnic probe. Postoperatively this was applied to the stoma facilitating direct measurements of graft mucosal flow. Measurements (perfusion units (PU)) were documented prior to implantation, post-reperfusion, postoperatively, during graft ischaemia, and in response to therapeutic interventions (dopexamine and phenylephrine infusions). RESULTS: Prior to transplantation, biological zero was established. Flow at five, 15, and 60 minutes after reperfusion was 74 (1.9) PU, 87.5 (3.3) PU, and 141.5 (2.5) PU, respectively. Postoperative mucosal flow was 141.6 (2.9) PU. Subsequent LDF measurement detected absence of flow even though clinical signs suggested only moderate reduction. This was confirmed on surgical re-exploration and facilitated prompt resection of a non-viable segment. Fluid and dopexamine administration resulted in a dose dependent improvement in flow, independent of blood pressure. Addition of phenylephrine increased total mucosal flow and unmasked a cyclical component. CONCLUSION: This case demonstrates the clinical value of LDF as an "alarm" to indicate graft perfusion failure and as a monitor for therapeutic interventions. Phenylephrine and dopexamine may both be of value in improving mucosal flow in the transplanted small bowel.
BACKGROUND: The microemulsion preconcentrate formulation of cyclosporine A (CsA) (Neoral) exhibits more uniform pharmacokinetics than the conventional formulation (Sandimmun; SIM). This randomized, open-label, U.K. multicenter study compared the efficacy, safety, and tolerability of Neoral and SIM in preventing acute rejection in de novo renal transplant recipients. METHODS: Adult cadaveric kidney recipients (n=293) received Neoral or SIM twice daily for 12 months. Initially identical Neoral and SIM doses were titrated, maintaining trough CsA levels within locally defined therapeutic limits. RESULTS: In the year after transplantation, acute rejection occurred in 34% of the Neoral and 47% of the SIM recipients (P=0.037). In the intent-to-treat population, fewer treatment failures (defined as acute rejection, graft loss, withdrawal, or death) occurred in the Neoral (45%) than the SIM recipients (58%) (P=0.015) and therapeutic CsA levels (> or =250 microg/L) were reached faster with Neoral than SIM (P=0.0017). Antibody treatment of refractory rejection was used slightly less in the Neoral group (Neoral: 10%; SIM: 12%). One-year patient and graft survival rates (excluding deaths with functioning grafts) were 95% and 88%, respectively, for Neoral and 96% and 89% for SIM. Both formulations were well tolerated. No differences were observed between therapies in the nature, frequency, or severity of adverse events. Neoral use was not associated with increased nephrotoxicity or excessive immunosuppression. CONCLUSIONS: Neoral reduced the incidence of acute rejection compared with SIM, without significant increases in adverse events. This was achieved without altering existing SIM protocols and was attributed to improved absorption of CsA from Neoral and less variability in whole blood CsA concentrations.
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The use of live donors in intestinal transplantation could potentially both reduce the severity of rejection responses against this highly immunogenic organ by better tissue matching and also reduce cold ischaemia times. These two advantages over cadaveric grafts could preserve mucosal integrity and reduce the risk of systemic sepsis from bacterial translocation. The disadvantages of live donation are the inherent risk to the donor and the compromise of using a shorter graft. Although only a handful of such cases have been performed, the success rate has been high and this is a therapeutic modality which should be explored further.
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