Nosratollah Nezakatgoo

Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation

Introduction. This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus (calcineurin inhibitor [CI]-sparing regimen) or mycophenolate mofetil (CI-free regimen) in high-risk cadaveric renal transplantation. Methods. Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen. The efficacy and toxicity profiles of these regimens were prospectively monitored and compared. Results. The study consisted of African Americans (71%), cadaveric donors (100%), donors aged more than 50 years (30%), and patients with delayed graft function (47%). At 1 year, patient survival, graft survival, and incidence of biopsy-proven acute rejection were 98%, 80%, and 10%, respectively, in the CI-sparing group and 100%, 89%, and 7%, respectively, in the CI-free group. Three-month protocol biopsies were performed in 41% (17/41) and 67% (20/29) of the subjects in the CI-sparing and CI-free groups, respectively. Subclinical rejection was detected in 6% (1/17) and 15% (3/20) of the subjects in the CI-sparing and CI-free groups, respectively. Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group. At 1 year, the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group (72.4±20.0 mL/min vs. 50.5±20.8 mL/min, P <0.01). The two regimens had similar toxicity profiles (hospital readmission, infection, wound complications, and metabolic complications). Conclusions. Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.

Long-term experience with simultaneous kidney-pancreas transplantation with portal-enteric drainage and tacrolimus/mycophenolate mofetil-based immunosuppression.

Abstract: Background/Aims:  Refinements in surgical techniques and advances in clinical immunosuppression have led to steadily improving results in pancreas transplantation (PTX). Although there is renewed interest in enteric exocrine drainage, most PTXs are performed with systemic venous delivery of insulin. To improve the physiology of PTX, we developed a novel technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal‐enteric [P‐E]). The purpose of the study was to analyse outcomes in patients undergoing PTX with P‐E drainage and contemporary immunosuppression.

Foregut cystic developmental malformation: New taxonomy and classification - Unifying embryopathological concepts

Foregut cystic developmental malformations are rare developmental anomalies. The problems inherent to these malformations are their presentation across specialties that include embryology, anatomy, pathology, thoracic foregut surgery, pediatric surgery and general abdominal surgery. The direct consequence of this variation has resulted in diverse terminology, classification and a failure to identify the correlation. The article aims to summarize and unify the embryological concepts of foregut cystic malformation, to suggest a generic title to the various groups of these interrelated disorders and a uniform use of nomenclature on the basis of unifying concepts of embryopathogeneis.

Prospective Observational Study of Sirolimus as Primary Immunosuppression After Renal Transplantation

Background. Sirolimus (SRL) is an important component of clinical immunosuppression in renal transplantation, but few international studies have examined how this agent is used in routine practice. Methods. Within a large prospective pharmacoepidemiological study, 718 de novo renal graft recipients treated with SRL in 65 centers in 10 countries were monitored for up to 5 years posttransplant to compare the principal outcomes and adverse effects by treatment regimen. Results. Principal treatment regimens were SRL without a calcineurin inhibitor (33%), SRL+cyclosporine A (CsA) (33%), and SRL+tacrolimus (TAC) (34%); 18% of subjects discontinued SRL, 124/718 (17%) developed biopsy-confirmed acute rejection (BCAR), 64/718 (9%) lost their graft, and 50/718 (7%) died during follow-up. Calculated creatinine clearance was 66±26 mL/min at 2 years. The most common adverse events were hypertension, hyperlipidemia, anemia, urinary tract infections, and diabetes. BCAR was significantly lower in subjects receiving SRL+TAC (hazard ratio [HR] 0.46, P=0.009) but not significantly lower in those receiving SRL+CsA (HR 0.62, P=0.102) compared with SRL without a calcineurin inhibitor. Graft loss or death did not significantly differ between treatment groups but were associated, respectively, with deceased donor grafts (HR 3.33, P<0.001) and increased age (HR 1.04, P<0.001). No improvement was observed in patients receiving mycophenolate mofetil in any treatment combination (HR 0.80, P=0.438 for BCAR; HR 0.93, P=0.849 for graft loss; and HR 0.75, P=0.531 for death). Conclusions. SRL is most commonly used in combination with mycophenolate mofetil, CsA, or TAC. BCAR was least common in subjects receiving SRL+TAC, but other outcomes seemed comparable between the treatment regimens in routine practice.

Use of a "composite" vascular access graft in a young child on hemodialysis.

Although arterio‐venous fistulae (AVF) are currently considered to be the first choice of permanent vascular access for hemodialysis, there are some patients who are not candidates for fistulae and synthetic grafts provide other options. The Thoratec (Vectra™) polyurethane vascular access graft is a new prosthetic graft that may be cannulated within days of insertion due to “self‐sealing” properties. However, a tendency for kinking at the suture site due to the strong elasticity of this graft, leading to undesirable complications such as thrombosis, have been reported. We describe a surgical modification of the anastomosis by interposing a segment of expanded polytetrafluoroethylene graft (ePTFE, Venaflo™) between the native vessels and the polyurethane graft sections in a pediatric patient. This modification may overcome the kinking complication associated with use of the polyurethane graft and the resulting thrombosis.

Liver transplant using donors after cardiac death: a single-center approach providing outcomes comparable to donation after brain death.

OBJECTIVES Organ donation after cardiac death remains an available resource to meet the demand for transplant. However, concern persists that outcomes associated with donation after cardiac death liver allografts are not equivalent to those obtained with organ donation after brain death. The aim of this matched case control study was to determine if outcomes of liver transplants with donation after cardiac death donors is equivalent to outcomes with donation after brain death donors by controlling for careful donor and recipient selection, surgical technique, and preservation solution. MATERIALS AND METHODS A retrospective, matched case control study of adult liver transplant recipients at the University of Tennessee/Methodist University Hospital Transplant Institute, Memphis, Tennessee was performed. Thirty-eight donation after cardiac death recipients were matched 1:2, with 76 donation after brain death recipients by recipient age, recipient laboratory Model for End Stage Liver Disease score, and donor age to form the 2 groups. A comprehensive approach that controlled for careful donor and recipient matching, surgical technique, and preservation solution was used to minimize warm ischemia time, cold ischemia time, and ischemia-reperfusion injury. RESULTS Patient and graft survival rates were similar in both groups at 1 and 3 years (P = .444 and P = .295). There was no statistically significant difference in primary nonfunction, vascular complications, or biliary complications. In particular, there was no statistically significant difference in ischemic-type diffuse intrahepatic strictures (P = .107). CONCLUSIONS These findings provide further evidence that excellent patient and graft survival rates expected with liver transplants using organ donation after brain death donors can be achieved with organ donation after cardiac death donors without statistically higher rates of morbidity or mortality when a comprehensive approach that controls for careful donor and recipient matching, surgical technique, and preservation solution is used.

Steroid-free Liver Transplantation Using Rabbit Antithymocyte Globulin Induction in 500 Consecutive Patients.

Background We have previously documented the efficacy of a steroid-free immunosuppression protocol using rabbit antithymocyte globulin (RATG) induction in orthotopic liver transplantation (OLT) with tacrolimus minimization. The purpose of this report is to demonstrate the benefits of this protocol in a large cohort of patients. Methods We evaluated outcomes of 500 consecutive OLT recipients who received RATG induction and a single dose of solumedrol given before the first dose of RATG. Mycophenolate mofetil was initiated postoperatively with delayed initiation of tacrolimus. Sirolimus replaced tacrolimus if serum creatinine remained above 2.0 mg/dL by day 7. Patients were weaned to tacrolimus or sirolimus monotherapy at 3 months. Mean model for end-stage liver disease (MELD) at transplantation was 22 ± 6. Results Forty-four percent of patients had hepatitis C. Posttransplant creatinine was highest at 1 month (1.43 ± 0.95 mg/dL) and improved to 1.26 ± 0.60 mg/dL (P < 0.05) at 2.5 years. Glomerular filtration rate was lowest at 1 month (65.6 ± 30.0) and improved by 1 year (72.7 ± 28.2, P < 0.01). Tacrolimus was initiated at 4.79 ± 13.3 days with a level of 4.95 ± 2.45 ng/mL at 1 year. One-year patient and graft survival were 92.8% and 89.6%, respectively, with a 3-year patient survival of 82.9%. Rejection occurred in 114 (22.8%) patients, 33 (6.6%) patients requiring steroids. Univariate and multivariate Cox proportional hazard analyses were performed to evaluate the effects of donor and recipient characteristics on patient and graft survivals. Pretransplant creatinine was consistently a statistically significant predictor for patient and graft survival. Conclusion This is the largest reported series of OLT recipients using a steroid-free protocol with RATG induction demonstrating excellent outcomes, low complication rates, and preservation of renal function.

Outcomes of Simultaneous Peritoneal Dialysis and Arteriovenous Fistula Placement in End-Stage Renal Disease Patients

Peritoneal dialysis (PD) interruption requiring hemodialysis (HD) is not uncommon and its frequently abrupt nature prevents timely creation of permanent HD access and avoidance of central venous catheters (CVC). We retrospectively studied a cohort of 24 end-stage renal disease (ESRD) patients (mean age 50.7 years, 83.3% African-Americans, 58.3% females, time on dialysis interquartile range [IQR] 0 – 65 days) who had simultaneous PD catheter insertion and backup arteriovenous fistula (AVF) creation between January 1, 2012, and December 31, 2013. The primary outcome of interest was the percent of patients receiving HD through the backup AVF at the time of PD interruption. A median (IQR) for PD catheter use after its insertion was 10.5 (2 – 20) days. After the mean follow-up of 19.6 months, 12 patients remained on PD, 2 patients received a kidney transplant, and 1 patient died. The overall AVF patency was 66.7%. A total of 9 (37.5%) patients had PD interruption requiring permanent (8 patients) or temporary (1 patient) HD after the mean (standard deviation [SD]) follow-up of 12.3 (8.2) months. Arteriovenous fistula was used as the initial access in 4 patients, and in 3 patients the original AVF was used after additional surgical revision. Forty-four percent of patients with a backup AVF fistula avoided CVC at the time of PD interruption requiring HD. The simultaneous AVF creation at the time of PD catheter insertion reduced but did not fully eliminate CVC at the time of PD interruption. Larger studies are needed to evaluate the utility of a backup AVF in PD patients.

A technique for the salvage of megafistulas allowing immediate dialysis access

Objective Almost two million individuals are undergoing renal replacement therapy worldwide, with hemodialysis being the common form. Many factors influence the primary patency of an arteriovenous fistula (AVF), including vessel size, fistula flow rates, cannulation practice, and thrombotic tendencies. Excess dilation of the AVF, resulting in the development of a megafistula, is a complication that can result in a need for AVF revision and subsequent failure. Methods The charts of patients who underwent autogenous AVF revision because of the development of a megafistula with aneurysmectomy and vein transposition by a single surgeon during a 7‐year period from 2009 through 2016 were reviewed. A technique is described in which after aneurysmorrhaphy, the repaired venous component of the AVF is transposed through a new tunnel while the vein is rotated 90 degrees. This allows the AVF to be accessed immediately, making placement of a tunneled dialysis catheter unnecessary. Results There were 102 patients included in the study, with follow‐up ranging from 7 to 95 months. In our cohort, 92 of the 102 revised AVFs (90.2%) maintained primary functional patency. Of the 102 patients who underwent this revision technique, there were 10 fistulas that subsequently failed after a mean of 29 months. There were only seven patients who experienced recurrent fistula dilation requiring repeated aneurysmectomy. Conclusions We describe a technique for management of the development of a megafistula that uses only autogenous tissue and, perhaps most important, eliminates the need for temporary dialysis catheter placement.