Impact of Donor and Recipient Cytokine Genotypes on Renal Allograft Outcome

Allelic differences in gene promoter or codifying regions have been described to affect regulation of gene expression, consequently increasing or decreasing cytokine production and signal transduction responses to a given stimulus. This observation has been reported for interleukin (IL)-10 (-1082 A/G; -819/-592 CT/CA), transforming growth factor (TGF)-beta (codon 10 C/T, codon 25 G/C), tumor necrosis factor (TNF)-alpha (-308 G/A), TNF-beta (+252 A/G), interferon (IFN)-gamma (+874 T/A), IL-6 (-174 G/C), and IL-4R alpha (+1902 G/A). To evaluate the influence of these cytokine genotypes on the development of acute or chronic rejection, we correlated the genotypes of both kidney graft recipients and cadaver donors with the clinical outcome. Kidney recipients had 5 years follow-up, at least 2 HLA-DRB compatibilities, and a maximum of 25% anti-HLA pretransplantation sensitization. The clinical outcomes were grouped as follows: stable functioning graft (NR, n = 35); acute rejection episodes (AR, n = 31); and chronic rejection (CR, n = 31). The cytokine genotype polymorphisms were defined using PCR-SSP typing. A statistical analysis showed a significant prevalence of recipient IL-10 -819/-592 genotype among CR individuals; whereas among donors, the TGF-beta codon 10 CT genotype was significantly associated with the AR cohort and the IL-6 -174 CC genotype with CR. Other albeit not significant observations included a strong predisposition of recipient TGF-beta codon 10 CT genotype with CR, and TNF-beta 252 AA with AR. A low frequency of TNF-alpha -308 AA genotype also was observed among recipients and donors who showed poor allograft outcomes.

Hepatic Artery Thrombosis in Live Liver Donor Transplantation: How to Solve - a Case Report

The decrease in the number of cadaveric donors has proved a limiting factor in the number of liver transplants, leading to the death of many patients on the waiting list. The living donor liver transplantation is an option that allows, in selected cases, increase the number of donors. One of the most serious complications in liver transplantation is hepatic artery thrombosis, in the past considered potentially fatal without urgent re-transplantation. A white male patient, 48 years old, diagnosed with hepatocellular carcinoma in chronic liver failure caused by hepatitis B virus, underwent living donor liver transplantation (right lobe). Doppler echocardiography performed in the immediate postoperative period did not identify arterial flow in the right branch, having been confirmed thrombosis of the right hepatic artery in CT angiography. Urgent re-laparotomy was performed, which consisted of thrombectomy and re-anastomosis of the hepatic artery with segmental splenic artery allograft interposition. The patient started anticoagulation and antiplatelet therapy with acetylsalicylic acid. Serial evaluation with Doppler echocardiography showed hepatic artery patency. At present, the patient is asymptomatic. One of the most devastating complications in liver transplantation, and particularly in living liver donor, is thrombosis of the hepatic artery; thus, early diagnosis and treatment is vital. The rapid intervention for revascularization of the graft avoids irreversible ischemia of the bile ducts and hepatic parenchyma, thus avoiding the need for re-transplantation.

Long-Term Survival (>25 Years) of Deceased Donor Kidney Transplant Recipients: a Single-Center Experience

INTRODUCTION: The aim of this preliminary work is to analyze the clinical features of 52 patients with a functional transplanted kidney for >25 years (all first transplant and all deceased donor recipients) and to compare with a similar though more complete study from Hôpital Necker-Paris 2012. METHODS: The mean graft survival at 25 years is 12.7% and at 30 years is 10%. The actual mean serum creatinine concentration is 1.3 mg/L. We analyzed recipient age (mean, 35.9 years) and gender (29 men and 23 women). Donor age was 26.7 ± 10.3 years. Seven patients (13.4%) were transplanted with 1 HLA mismatch, 42.3% with 2 mismatches, and 44.2% with 3 mismatches. Mean cold ischemia time was 15.45 ± 7.7 hours. Of the recipients, 76% had immediate graft function; 38% experienced 1 acute rejection episode and 4 patients had 2 rejection crises. The initial immunosuppressive regimen was azathioprine (AZA) + prednisolone (Pred) in 14 patients, cyclosporin (CSA) + Pred in 13 patients, and CSA + AZA + Pred in 25 patients. Of these patients, 19% maintained their initial regimen, and 54% (28 patients) were very stable on a mixed CSA regimen for >25 years. RESULTS: We present the major complications (diabetes, neoplasia, and hepatitis C virus positivity). CONCLUSION: Our results in deceased donor kidney recipients for >25 years are similar to the mixed population (deceased donors and living donors) presented by the Necker group, although 54% of our patients remain on CSA immunosuppression, contradicting the idea that its use is not compatible with good long-term kidney function in transplant recipients.

Orbital Exenteration for Eyelid Skin Carcinoma

Exenteration of the orbit is a disfiguring and destructive procedure; it is generally performed for orbital malignancies and often provides a significant reconstructive challenge. Our purpose was to evaluate the clinical indications for orbital exenteration in a tertiary referral center and to assess the reconstructive options employed. A retrospective nonrandomized analysis was performed, selecting all patients undergoing orbital exenteration over a 5-year period, between January 2005 and January 2010. Patient demographics, tumor characteristics, and reconstructive techniques used were evaluated. Twenty patients with a mean age of 76.5 years underwent total orbital exenteration. Basal cell carcinoma was the main operative indication (45%), followed by squamous cell carcinoma (15%). Reconstructive techniques included cover of the raw orbital cavity with a temporal muscular flap in all cases followed with split skin grafting (25%), bilaterally pedicle V-Y advancement flap (10%) and a fasciocutaneous island flap of the retroauricular region (65%). Twenty percent of patients had local complications and all were treated in a satisfactory fashion. Eyelid skin tumors remain an important cause of orbital exenteration. Temporal muscle flap is a reliable and stable reconstructive solution after orbital exenteration and additional aid is supplied with skin grafts or local flaps. This technique ensures a good aesthetic outcome and better situation for later complementary treatments and minimal associated donor site morbidity.

Morphometric Analysis of the Extensor Tendons of the Hallux and Potential Implications for Tendon Grafting

Although several tendon sources are available for reconstructive surgical procedures, all have one or more shortcomings. The aim of this work was to evaluate if the extensor tendons of the hallux showed anatomical characteristics that could make them an additional source for tendon grafting procedures.The authors performed a detailed morphometric analysis of the extensor tendons of the hallux in 26 lower limbs in order to evaluate the putative association of anatomical variants with hallux valgus, and to attempt to assess the feasibility of using part of the extensor apparatus of the hallux as a source of tendon for grafting procedures.An accessory extensor hallucis longus ten-don was found in 92.3% of cases. The extensor hallucis brevis tendon length was 10.5 ± 0.6 cm; its width was 0.5 ± 0.1 cm, and its thickness varied between 1-2 mm, making it a potentially good candidate as a source of ten-don grafts. Several anatomical variations were observed, namely the fusion of the tendons of the extensor hallucis brevis and the accessory extensor hallucis longus muscles in the distal part of the foot.This new therapeutic option, if implemented, would possibly increase the supply of autogenous donor tissue for reconstructive procedures, thereby enhancing the reconstructive surgeon’s armamentarium.

Abdominoplasty and Thoraco-Epigastric Flaps for Large Anterior Trunk Defects after Dermatofibrosarcoma Protuberans Wide Resection: Two Illustrative Cases

INTRODUCTION: Excision of large dermatofibrosarcoma protuberans in the anterior aspect of the trunk often results in large surgical defects that frequently dictate the need for microsurgical reconstruction. However, this option is not always available. PRESENTATION OF CASE: The authors describe two patients with very large anterior trunk dermatofibrosarcoma protuberans: one in the epigastric region and the other in the hypogastric region. In the patient with the hypogastric tumor, a classical abdominoplasty flap associated with umbilical transposition was used to cover the skin defect after muscle and fascial plication, and placement of a polypropylene mesh. In the patient with the epigastric tumor, a synthetic mesh was also placed, and the skin and subcutaneous defect was reconstructed with a reverse abdominoplasty flap and two thoraco-epigastric flaps. In both cases, complete closure was possible without immediate or late complications. DISCUSSION: The local options described in this paper present several potential advantages compared to microsurgical reconstruction, namely they are easier and faster to perform and teach; they provide a good skin color and texture match; they are not associated with distant donor site morbidity; follow-up is usually less cumbersome; the post-operative hospital stay tends to be shorter; they are less costly; they are less prone to complete failure. CONCLUSION: The authors believe that these two patients clearly show that local flaps, although frequently neglected, continue to be valid options for reconstructing large anterior trunk defects, even in the current era of microsurgery enthusiasm.

Chronic Allograft Dysfunction - Is There a Treatment?

BACKGROUND: The major causes of renal transplant loss are death and chronic allograft dysfunction (CAD). The aims of this study were to determine the incidence of CAD in our population and the relation between allograft survival and immunosuppressive regimens. METHODS: We studied retrospectively 473 patients who received deceased donor kidney transplants with at least 1 allograft biopsy between January 1990 and May 2007. Clinical data included age, gender, biopsy data, and immunosuppression before and after kidney biopsy. Mean age was 45.4 +/- 12.7 years including 65% males with a mean follow-up of 6.7 +/- 4.5 years. CAD was observed in 177 of 473 biopsies: 48 patients showed interstitial fibrosis (IF); 101 chronic rejection (CR); 16 transplant glomerulopathy (TG); and 12, CR and TG. Mean follow-up since the discovery of the histologic feature was 60.5 +/- 50.5 months for IF; 38.3 +/- 40.8 for CR, and 18.2 +/- 19.2 for TG. RESULTS: CAD, which was more common in younger patients (P = .03), correlated upon univariate and multivariate analysis with CKD stage 5d development (P < .001). Deposition of C4d in peritubular capillaries was more frequent among CAD patients (P = .004), an association with particular relevance to recipients with CR (P = .02) and TG (P < .001). When we analyzed CAD subpopulation, we observed a positive correlation between allograft survival and immunosuppression modification after biopsy. Substitution of sirolimus (40/177) was shown in univariate, multivariate and Cox regression analyses to be a renal protector (P < .002). Allograft survival was also correlated with initial mycophenolate mofetil versus azathioprine, (62/177) immunosuppression (P < .001). CONCLUSION: CAD, a frequent histologic feature, may benefit from sirolimus conversion.

Zero-Time Kidney Histology Predicts Early Graft Function

Our purposes are to determine the impact of histological factors observed in zero-time biopsies on early post transplant kidney allograft function. We specifically want to compare the semi-quantitative Banff Classification of zero time biopsies with quantification of % cortical area fibrosis. Sixty three zero-time deceased donor allograft biopsies were retrospectively semiquantitatively scored using Banff classification. By adding the individual chronic parameters a Banff Chronic Sum (BCS) Score was generated. Percentage of cortical area Picro Sirius Red (%PSR) staining was assessed and calculated with a computer program. A negative linear regression between %PSR/ GFR at 3 year post-transplantation was established (Y=62.08 +-4.6412X; p=0.022). A significant negative correlation between arteriolar hyalinosis (rho=-0.375; p=0.005), chronic interstitial (rho=0.296; p=0.02) , chronic tubular ( rho=0.276; p=0.04) , chronic vascular (rho= -0.360;P=0.007), BCS (rho=-0.413; p=0.002) and GFR at 3 years were found. However, no correlation was found between % PSR, Ci, Ct or BCS. In multivariate linear regression the negative predictive factors of 3 years GFR were: BCS in histological model; donor kidney age, recipient age and black race in clinical model. The BCS seems a good and easy to perform tool, available to every pathologist, with significant predictive short-term value. The %PSR predicts short term kidney function in univariate study and involves extra-routine and expensive-time work. We think that %PSR must be regarded as a research instrument.

Transplantation in Highly Sensitised Patients Treated with Intravenous Immunoglobulin and Rituximab

Renal transplant in highly sensitised patients is associated with increased morbidity. The aim of this retrospective study was to evaluate the clinical evolution of 30 highly sensitised deceased donor kidney transplants and the influence of different timing of B cell directed treatment and its importance in the outcome of these patients. All recipients had negative complement dependent lymphocytotoxicity cytotoxic T cell crossmatch and no identified anti human leucocyte antigen class I donor specific antibodies. T cell flow crossmatch was performed within 24h of transplantation with serum obtained pretransplant (historic, recent or baseline). Posttransplant flow crossmatch were performed prospectively starting on the 3rd posttransplantation day. The immunosuppressive regime included thymoglobulin, tacrolimus, mycofenolate mofetil and steroids. Positive flow crossmatch occurred in 20/29 patients by the 3rd posttransplantation day, and in 17/27 patients after the 3rd posttransplantation day. All patients were started on intravenous immunoglobulin before transplantation: in nine patients (group A) at 400mg/kg/day for five days; in the remaining 21 patients (group B), as a continued infusion of 2g/kg during 48h. In group A, Rituximab was added only in the presence of antibody mediated rejection; in group B, introduced on the 3rd posttransplantation day whenever a positive flow crossmatch (with serum obtained pre or posttransplant) was reported. Antibody mediated rejection was observed in 44.4% of patients in group A, and 19% of those in group B. Mean follow-up was 12.2±5.5 months. Overall allograft survival was 76.6%, 81% in group B, and 66.6% in group A. At last follow up, mean serum creatinine was 1.3±0.6 mg/dl. Renal transplantation with pretransplant positive flow crossmatch is highly associated with antibody mediated rejection, despite introduction of intravenous immunoglobulin pretransplantation. However high dose intravenous immunoglobulin for 48h plus Rituximab by the 3rd posttransplantation day reduce the incidence of antibody mediated rejection by more than 50% and allowed for allograft survival of 81% at one year, with an excellent renal function.