Ivo Tzvetanov

Living donor kidney transplantation across positive crossmatch: The University of Illinois at Chicago Experience

Background. To increase living donation for kidney transplantation, we investigated desensitization of recipients with positive crossmatch against a potential living donor. Methods. Between June 2001 and March 2007, 57 consecutive sensitized candidates for kidney transplantation, with crossmatch positive potential living donors, were treated with various desensitization protocols. All patients received plasmapheresis every other day with intravenous immune globulin 100 mg/kg starting 1 week before the scheduled transplant. Postoperatively, the recipients continued to receive every other day plasmapheresis with intravenous immune globulin for the initial week. Immunosuppression therapy consisted of induction with thymoglobulin and a combination of tacrolimus, mycophenolate, and corticosteroids. Results. Six patients failed to convert with pretransplant immunomodulation and were not transplanted; 51 underwent live donor kidney transplant. Mean follow-up was 23 months and 36 patients have more than 1-year follow-up. One-year patient and graft survivals were 95% and 93%, respectively. There were 25 episodes of biopsy-proven or clinically presumed rejection in 22 patients in the first year. Of the 17 biopsy-proven episodes, 12 were antibody-mediated rejection and five were acute cellular rejection. Of the patients with antibody-mediated rejection (biopsy proven or empiric), two patients (12%) lost their graft by 1 year. The median modification of diet in renal disease at 6 and 12 months was 55 mL/min (range 9–104 mL/min) and 48 mL/min (range 8–99), respectively. Conclusions. Despite increased rejection rates, graft and patient survivals indicate that desensitization of positive crossmatch patients is a reasonable alternative for a sensitized patient who could potentially wait 10 or more years for a suitable cadaveric kidney.

Minimally Invasive Robotic Kidney Transplantation for Obese Patients Previously Denied Access to Transplantation

Epidemiological data indicate that 20-50% of patients on dialysis for end-stage renal disease (ESRD) are obese (body mass index [BMI] ≥30 kg/m2) (1). Obese patients with chronic renal failure have longer wait times until kidney transplantation (2) and inferior patient outcomes (3-7). In the US, for example, patients with a BMI 40 kg/m2 (2). Higher BMIs in kidney transplant recipients are associated with excess risk of surgical site infections (SSIs), which negatively impact graft survival (8). Obesity is also associated with comorbidities such as diabetes, although data on whether obesity increases mortality in kidney transplanted patients remains unclear (8,9). Provider perceptions of these risks accompanied by the expectation of some centers to give obese patients time to lose weight are the main reasons why a number of transplant centers are reluctant to list obese patients for transplantation (2,10). Unfortunately, many of these obese patients have diabetes and hypertension likely secondary to their obesity (11) and such patients who remain on dialysis have a very high mortality rate. The 5-year mortality rate for diabetic and hypertensive dialysis patients is 75 and 70%, respectively (1). A recent study demonstrated that obese patients who did not present with any SSIs had the same kidney transplant success rate as patients with a normal BMI (8). If surgical procedures could be developed that prevent SSIs and demonstrate successful outcomes, transplant centers may become less reluctant to list obese patients for kidney transplantation. Although any benefit would still have to be weighed against potential increased risks from obesity-related comorbidities. The prevalence of obesity and ESRD is higher among racial and ethnic minority populations, including African-Americans and Hispanics, compared to Non-Hispanic whites (12-15). These observations suggest developing kidney transplantation options for obese patients with ESRD may also help to reduce health disparities in racial and ethnic minorities. We therefore developed a new, minimally invasive, robotic-assisted kidney transplantation method using a short epigastric incision. This method avoids any incision in the infection prone lower quadrants of the abdomen. We hypothesized a priori that the robotic approach would reduce SSIs and improve outcomes in obese kidney transplant patients. Herein, we present our experience and outcomes of the patients undergoing minimal invasive, robotic kidney transplantation at a single institution compared to patients who underwent the conventional open procedure.

Robotic transabdominal kidney transplantation in a morbidly obese patient.

Kidney transplantation in morbidly obese patients can be technically demanding. Furthermore, morbidly obese patients experience a high rate of wound infections and related complications, which mostly result from the longer length and extent of the incision. These complications can be avoided through minimally invasive surgery; however, conventional laparoscopic instruments are unsuitable for the safe performance of a kidney transplant in morbidly obese patients. Herein, we report the first minimally invasive, total robotic kidney transplant in a morbidly obese patient. A left, deceased donor kidney was transplanted into a 29‐year‐old woman with a body mass index (BMI) of 41 kg/m2 who had been on hemodialysis for 5 years. The operation was performed intraabdominally using the DaVinci Robotic Surgical System with 4 trocars and a 7 cm midline incision. The operative time was 223 min, and the blood loss was less than 50 cc. The kidney had immediate graft function. No perioperative complications were observed, and the patient was discharged on postoperative day 5 with normal kidney function. Minimally invasive access and robotic technology facilitated the safe performance of a successful kidney transplant in a morbidly obese patient.

Robot‐assisted right lobe donor hepatectomy

Recent advances in robotic surgical technology have enabled application to complex surgical procedures. Following extensive institutional experience with major robotic liver resections, we determined that it was safe to apply this technology to right lobe donor hepatectomy (RLDH). The procedure was performed using the Da Vinci Robotic Surgical System, in an entirely minimally invasive fashion, during which the liver graft was safely extracted through a limited lower abdominal incision. Both donor and recipient recovered well, without acute complications. To our knowledge, this is the first case reported in the literature. The technical feasibility of this minimally invasive approach is demonstrated, exemplifying the novel exciting opportunities offered by robotic technology.

Current status of living donor small bowel transplantation.

Purpose of reviewTo analyze the current status of living donor intestinal transplantation (LDIT) as a treatment option for intestinal failure. Recent findingsLong-term outcomes from LDIT and combined living donor intestinal/liver transplantation (CLDILT) are comparable with those from transplantation using deceased donors. In certain life-threatening situations, especially in pediatric patients, this strategy may offer potential advantages. SummaryAccording United Network for Organ Sharing (UNOS) data children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list compared with all candidates for solid organ transplantation. Elective nature of CLDILT offers multiple advantages for this patient population. LDIT also could be life-saving option for patients with intestinal failure who run out of venous access. Optimal timing, short ischemia time and good human leukocyte antigen (HLA) matching may contribute to lower postoperative complications. Current literature suggests that living intestinal donors experience very low morbidity and high level of satisfaction.

Interleukin-2 receptor blockade with humanized monoclonal antibody for solid organ transplantation.

Importance of the field: Induction therapy has reduced the incidence of acute rejection compared with historical standards. The potency of currently available induction immunosuppression is not without risk and should be carefully considered. Induction with daclizumab, an IL-2 receptor antagonist, has been used safely and effectively for over 10 years across different transplant types. As a result of daclizumab use, transplant centers are able to implement steroid-sparing or calcineurin minimization protocols. Unfortunately, the manufacturing costs have resulted in withdrawal of this agent from the market reducing the options for patients undergoing transplantation. Areas covered in this review: This review will update the reader on recently published daclizumab studies in adult solid organ transplant recipients, focusing on comparative studies with other induction agents. What the reader will gain: This paper will provide a summary of comparative studies between daclizumab and other induction therapies focusing on their efficacy and safety. Take home message: Novel applications, such as long-term use in combination with calcineurin-inhibitor dose reduction and its value in the treatment of acute or chronic rejection have yet to be explored. Since daclizumab has been withdrawn from the market, future IL-2 receptor blockade will have to be achieved with basiliximab, which is a chimeric, monoclonal antibody directed against the same epitope.

State of the Art of Robotic Surgery in Organ Transplantation

Within the last two decades the application of minimally invasive surgical technologies has shown significant benefits when it comes to complex surgical procedures. Lower rates of complications and higher patient satisfaction are commonly reported. Until recently these benefits were inaccessible for patients with solid organ transplantation, because conventional laparoscopy was seen as nonapplicable in such technically demanding procedures. The introduction of the da Vinci Robotic Surgical System, with its inherent advantages, has expanded the ability to complete solid organ transplantation in a minimally invasive fashion. Robotic applications in kidney, pancreas, and liver transplantation have been reported. The initial results showed the viability of this technique in the field. The most extensive experience has been described in kidney transplantation. Over 700 donor nephrectomies and more than 70 renal transplants have been performed successfully with the robotic system. The proven advantage of the robotic technique, especially in obese kidney recipients, is a significantly lower rate of surgical site infection, which in these highly immunosuppressed patients is reflected in superior outcomes. The first results in pancreas transplantation and living donor hepatectomy are very promising; however, larger series are needed in order to address the value of the robotic surgery in these areas of solid organ transplantation.

Lessons learned in pediatric small bowel and liver transplantation from living-related donors.

Background. Children are the primary candidates for intestinal transplant with more than 70% requiring a combined liver-bowel transplant. We report our single-center experience with living donor intestinal transplantation (LDITx) and combined living donor intestinal and liver transplant (CLDILTx) in pediatric patients. Patients and Methods. Between October 2002 and June 2006, 13 living donor intestinal grafts were transplanted in 10 recipients. In five cases CLDILTx was performed. The intestinal grafts consisted of a 150-cm segment of ileum, whereas the liver transplant was completed using standard left lateral grafts. Results. No complications occurred in any donors. In CLDILTx recipients, the patient survival at 1 and 2 years was 100%, the liver graft survival 100%, and the bowel graft survival 80%; the patient who lost the initial intestinal graft was successfully retransplanted. In LDITx recipients, the patient and graft survival at 1 and 3 years were 60% and 50%, respectively. Two isolated LDITx recipients, both 6 months of age and low body weight (mean, 6 vs. 9 kg) died within 4 months posttransplant. One LDITx recipient developed chronic rejection 3.5 years after the original transplant and died after retransplant. All patients who are alive with functioning grafts are currently on full enteral feeding without need for any intravenous supplementation, except for a recipient of CLDILTx, currently on total parenteral nutrition for late fistula. Conclusions. The early outcomes of intestinal transplantation from living donors are promising, particularly for candidates in need of CLDLITx. In this subgroup, the elimination of the high mortality on the cadaver waiting list (∼30%) represents a substantial advantage.

Multifocal cutaneous and systemic plasmablastic lymphoma in an infant with combined living donor small bowel and liver transplant.

Abstract:  Small bowel allograft recipients have a relatively high risk (approximately 20%) of developing PTLD. Onset of PTLD is usually soon after transplant (median of eight months). Children are at a higher risk than adults. Although PBL was originally described in 1997 by Delecluse et al. as a human immunodeficiency virus‐associated neoplasm typically presenting in the oral cavity, it is now recognized as a PTLD. We describe an unusual and interesting case and to our knowledge the first case of an infant who developed diffuse multifocal cutaneous and systemic PBL shortly after small bowel and liver transplant. We report a case of a 14‐month‐old female child who received a small bowel and liver transplant from her father. She had excellent graft function with no rejection episodes. Five months post‐transplant she developed a sudden gastrointestinal bleed and was noted to have a constantly rising EBV titer despite ongoing maximal antiviral therapy. A patchy erythematous rash was noted on her abdomen that was diagnosed as PBL–PTLD. By the time of this diagnosis, she had developed multiorgan failure unresponsive to therapy.

The Use of Bortezomib as a Rescue Treatment for Acute Antibody-Mediated Rejection: Report of Three Cases and Review of Literature

Antibody-mediated rejection (AMR) typically occurs early after transplantation in approximately 5%-7% of recipients. The literature reports suggest that 12%-37% of kidney transplant recipients with acute AMR do not respond to treatment and eventually lose their grafts. The proteasome inhibitor bortezomib is currently approved by the Food and Drug Administration for the treatment of multiple myeloma. It has been demonstrated both in vitro and in vivo to possess apoptotic properties against mature plasma cells. Herein we have described a series of 3 patients with positive cross-matches who developed early AMR after kidney transplantation. Bortezomib rescue treatment was administered after the patients failed to respond to plasmapheresis/intravenous immunoglobulin and splenectomy. All 3 patients responded with full, durable recovery of renal function. In conclusion, bortezomib is useful to treat refractory AMR after kidney transplantation.