PROviding Better ACcess To ORgans: A comprehensive overview of organ-access initiatives from the ASTS PROACTOR Task Force.

The American Society of Transplant Surgeons (ASTS) PROviding better Access To Organs (PROACTOR) Task Force was created to inform ongoing ASTS organ access efforts. Task force members were charged with comprehensively cataloguing current organ access activities and organizing them according to stakeholder type. This white paper summarizes the task force findings and makes recommendations for future ASTS organ access initiatives.

Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.

New insights into mechanisms of spontaneous liver transplant tolerance: the role of Foxp3-expressing CD25+CD4+ regulatory T cells.

Liver allografts in mice are accepted across MHC barriers without requirement for immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we investigated the role of Foxp3-expressing CD25(+)CD4(+) regulatory T cells (Treg) in the induction of murine liver transplant tolerance. Foxp3(+)CD25(+)CD4(+) T cells were increased in liver grafts and recipient spleens from day 5 to day 100 posttransplantation, associated with enhanced CTLA4 and TGF-beta expression and IL-4 production. Depletion of recipient CD25(+)CD4(+) T cells using anti-CD25 mAb (250 microg/day) induced acute liver allograft rejection. This was associated with a decreased ratio of Foxp3(+) Treg: T effector cells, decreased IL-4 and elevated IL-10 and IL-2 production by graft-infiltrating T cells, and reduced apoptotic activity of graft-infiltrating CD4(+) and CD8(+) T cells in anti-CD25-mAb-treated recipients. Thus, the data suggest that Foxp3(+)CD25(+)CD4(+)Treg are involved in spontaneous acceptance of liver allografts in mice. The ratio of Treg to T effector cells appears to determine liver transplant outcome. CTLA4, IL-4, TGF-beta and apoptosis of graft-infiltrating T cells are also associated with liver transplant tolerance and may contribute, at least in part, to the mechanisms of Treg-mediated immune regulation in this model.

Ureteral complications in renal transplantation: a comparison of the Lich-Gregoir versus the Taguchi technique.

OBJECTIVE: Modifications of the Lich-Gregoir extravesical ureteroneocystostomy have become the standard technique for management of the ureter during renal transplantation. We performed a comparative outcome examination of the standard Lich-Gregoir technique and the Taguchi or "one-stitch" technique. METHODS: We reviewed our experience at the University of Washington with the Taguchi (one-stitch, Minnesota) extravesical reimplant technique that involves tacking the distal ureter to the bladder mucosa with a single absorbable stitch. RESULTS: During a 3.5-year period, 330 renal transplants were performed and in 73 cases a Taguchi ureteral anastomosis was employed rather than the Lich-Gregoir technique (238 cases). The overall complication rate for the Taguchi technique was 23% (n = 16) as opposed to 7.1% for the Lich-Gregoir technique. When comparing the Taguchi to the Lich-Gregoir technique, there was a significant increase in hematuria and ureteral complications (P = .002, .012). In a multivariate analysis, the Taguchi technique was a significant risk factor for both hematuria and ureteral complications. CONCLUSIONS: In summary, our limited experience with Taguchi ureteroneocystostomy resulted in dramatically higher complication rates than the modified the Lich-Gregoir technique.

The role of Foxp3+ regulatory T cells in liver transplant tolerance.

The liver has long been considered a tolerogenic organ that favors the induction of peripheral tolerance. The mechanisms underlying liver tolerogenicity remain largely undefined. In this study, we characterized Foxp3-expressing CD4+ CD25+ regulatory T cells (Treg) in liver allograft recipients and examined the role of Treg in inherent liver tolerogenicity by employing the mouse spontaneous liver transplant tolerance model. Orthotopic liver transplantation was performed from C57BL/10 (H2b) to C3H/HeJ (H2k) mice. The percentage of CD4+ CD25+ Treg was expanded in the liver grafts and recipient spleens from day 5 up to day 100 posttransplantation, associated with high intracellular Foxp3 and CTLA4 expression. Immunohistochemistry further demonstrated significant numbers of Foxp3+ cells in the liver grafts and recipient spleens and increased transforming growth factor beta expression in the recipient spleens throughout the time courses. Adoptive transfer of spleen cells from the long-term liver allograft survivors significantly prolonged donor heart graft survival. Depletion of recipient CD4+ CD25+ Treg using anti-CD25 monoclonal antibody (250 microg/d) induced acute liver allograft rejection, associated with elevated anti-donor T-cell proliferative responses, CTL and natural killer activities, enhanced interleukin (IL)-2, interferon-gamma, IL-10, and decreased IL-4 production, and decreased T-cell apoptotic activity in anti-CD25-treated recipients. Moreover, CTLA4 blockade by anti-CTLA4 monoclonal antibody administration exacerbated liver graft rejection when combined with anti-CD25 monoclonal antibody. Thus, Foxp3+ CD4+ CD25+ Treg appear to underpin spontaneous acceptance of major histocompatability complex- mismatched liver allografts in mice. CTLA4, IL-4, and apoptosis of alloreactive T cells appear to contribute to the function of Treg and regulation of graft outcome.

Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance.

Liver allografts are accepted spontaneously in all mouse strain combinations without immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we examined the effect of CD4+ CD25+ T regulatory cells (Treg) on the induction of mouse liver transplant tolerance. Orthotopic liver transplantation was performed from B10 (H2b) to C3H (H2k) mice. Depleting rat anti-mouse CD25 mAb (PC61) was given to the donors or recipients (250 microg/d IP) pretransplant or to the recipients postoperatively. At day 5 posttransplantation, both effector T cells (mainly CD8) and CD4+ CD25+ Treg were increased in the liver allografts and host spleens compared to naïve mice. Anti-CD25 mAb administration, either pretransplantation or posttransplantation, reduced the ratio of CD4+ CD25+ Treg to the CD3 T cells of liver grafts and recipient spleens and induced liver allograft acute rejection compared to IgG treatment. Anti-CD25 mAb administration elevated anti-donor T-cell proliferative responses and CTL and NK activities of graft infiltrates and host splenocytes; reduced CTLA4, Foxp3, and IDO mRNA levels; increased IL-10 and IFN-gamma; and decreased IL-4 mRNA levels in the livers or host spleens. The number of apoptotic T cells was reduced significantly in the liver grafts and treated host spleens. Therefore, anti-CD25 mAb administration changed the balance of CD4+ CD25+ Treg to activated T cells of liver graft recipients, preventing liver transplant tolerance. This was associated with enhanced anti-donor immune reactivity, downregulated Treg gene expression, and reduced T cell apoptosis in the grafts and host spleens.

Optimizing a canine survival model of orthotopic lung transplantation.

INTRODUCTION: While acute models of orthotopic lung transplantation have been described in dogs, the technical considerations of developing a survival model in this species have not been elaborated. Herein, we describe optimization of a canine survival model of orthotopic lung transplantation. METHODS: Protocols of orthotopic left lung transplantation and single lung ventilation were established in acute experiments (n=9). Four dogs, serving as controls, received autologous, orthotopic lung transplants. Allogeneic transplants were performed in 16 DLA-identical and 16 DLA-mismatched unrelated recipient dogs. Selective right lung ventilation was utilized in all animals. A Malecot tube was left in the pleural space connected to a Heimlich valve for up to 24 hours. To date, animals have been followed up to 24 months by chest radiography, pulmonary function tests, bronchoscopy with lavage, and open biopsies. RESULTS: Long-term survival was achieved in 34/36 animals. Two recipients died intraoperatively secondary to cardiac arrest. All animals were extubated on the operating table, and in all cases the chest tube was removed within 24 hours. Major complications included thrombosis of the pulmonary artery and subcritical stenosis of bronchial anastamosis. One recipient underwent successful treatment of a small bowel intussusception. CONCLUSIONS: We report our experience in developing a survival canine model of orthotopic single lung transplantation. While short-term survival following canine lung transplantation is achievable, we report particular considerations that facilitate animal comfort, early extubation, and lung reexpansion in the immediate postoperative period, further optimizing use of this species for experimental modeling of long-term complications after lung transplantation.

Urologic aspects of kidney-pancreas transplantation.

The population of pancreas transplant recipients is growing steadily, and urologists most likely will be confronted with their unique anatomy and metabolic complications. The principles of diagnosis and management of these patients can be applied to other transplant recipients (e.g., heart, lung, and liver) who also are maintained on life-long immunosuppression and in whom urologic pathology develops commensurate with the incidence in the general population.

Outcomes with the selective use of enteric exocrine drainage in pancreas transplantation.

BACKGROUND: Bladder drainage of the exocrine secretions of pancreas transplants has been the standard of practice as it affords the ability to monitor for rejection and is thought to be associated with decreased morbidity. Recently, there has been renewed interest in avoiding the urinary tract complications and metabolic derangements that accompany bladder drainage by draining pancreatic exocrine secretions into the jejunum (enteric drainage). We sought to determine whether enteric drainage of pancreas transplants is safe and offers advantages without compromise in graft function or longevity. METHODS: We retrospectively reviewed all pancreas transplants performed at the University of Washington between 2000 and 2003. Selection of the exocrine drainage method was based on the length of cold ischemia time and whether the pancreas was transplanted alone or in combination with a kidney. Pearson's chi-square and Fisher's Exact tests were used for statistical comparisons in complications or rejections between the groups. RESULTS: Thirty-four pancreas transplants were performed with exocrine drainage into the bladder used in 17 and enteric drainage in 17. The complication rate was 53% in the bladder-drained group and 41% (P=.49) in the enteric-drained group. The incidence of pancreas rejection was 24% in the bladder-drained versus 29% in the enteric-drained patients (P=.50). One graft failed, which was in the bladder cohort. CONCLUSIONS: We found comparable rejection and complication rates between groups. We conclude that enteric drainage is safe when used selectively, and entails no increased risks compared with bladder drainage.

The Mitrofanoff catheterizable channel: patient acceptance.

A review of our experience with the Mitrofanoff catheterizable channel, with emphasis on patient acceptance and preference, is presented. Continent catheterizable channels using the Mitrofanoff principle were created in 35 patients (mean age 9.1 years, range 2 to 21). Mean followup was 22 months (range 1 to 60). Followup data are available for 33 patients. We used the appendix, ureter, fallopian tube and tube of stomach to construct the channel. All 33 patients used the Mitrofanoff catheterizable channel without difficulty for at least 3 months postoperatively. A total of 16 patients (48%) can empty the bladder only by Mitrofanoff catheterization and do so without difficulty. All 11 patients (33%) who have the potential to catheterize either the Mitrofanoff channel or urethra choose to catheterize the Mitrofanoff channel preferentially. The patient not using Mitrofanoff catheterization had stomal stenosis 12 months postoperatively and elected to perform urethral catheterization rather than undergo surgical repair. Five patients (15%) can void but all use the Mitrofanoff catheterizable channel to monitor post-void residual volumes. This study shows a high acceptance rate for patients receiving a continent catheterizable stoma.

Endoscopic treatment of bladder outlet obstruction in men after pancreas transplantation.

PURPOSE: Diabetic cystopathy comprises a spectrum of voiding dysfunction. The usual clinical manifestations are impaired bladder sensation and detrusor contractility. Diabetic cystopathy is present in as many as 43 to 85% of patients undergoing pancreas transplantation. We evaluated endoscopic management of bladder outlet obstruction for adjuvant treatment of urological complications after pancreas transplantation. MATERIALS AND METHODS: We evaluated 10 men with recurrent urological complications, including bladder leak, urinary tract infection, the dysuria/urethritis syndrome and reflux nephropathy, after pancreas transplantation. Evaluation consisted of peak flow rate, post-void residual and written questionnaires in all cases, and preoperative urodynamics in 2. All patients had signs and symptoms of bladder outlet obstruction at post-transplant presentation and underwent bladder neck incision, direct visual internal urethrotomy, limited transurethral resection of the bladder neck or transurethral resection of the prostate. Hospital costs, including operating room, laboratory, pharmacy, hospital room occupancy, anesthesia and radiology fees, were obtained from the University of Washington. RESULTS: Mean peak flow rate plus or minus standard deviation increased from 10.1+/-3.2 to 21.0+/-5.1 cc per second and post-void residual decreased from 259.2+/-38.6 to 43.6+/-36.8 cc after endoscopic intervention. Of the patients 4 presented early (mean 4.3 months) after transplantation with bladder leak or reflux nephropathy, while late presentation (mean 43 months) was associated with recurrent urinary tract infection, the urethritis/dysuria syndrome and more obstructive symptoms. Complications resolved in all cases after surgery and enteric conversion, which costs 5-fold more than endoscopic intervention, was avoided. CONCLUSIONS: Recurrent urological complications warrant early evaluation for occult bladder dysfunction. Endoscopic procedures to relieve outlet obstruction are beneficial in alleviating recurrent urological complications in men after pancreas transplantation. This cost-effective and low morbidity procedure may obviate the need for enteric conversion in some male transplant recipients.

Premature emission after spinal cord injury.

Physicians and psychologists almost always treat premature emission or ejaculation as a psychological problem. We report on 6 men who had sudden onset of severe premature emission after spinal cord injury. All men suffered spinal cord injury related to trauma at the T12-L1 level, and had areflexic bladders after the injury. Two men had normal penile sensation. None of the men had premature ejaculation before injury with average time of intercourse of 10 to 20 minutes before organsm. After the injury they noticed emission before or at vaginal entry. Two patients reported emission with any sexual thoughts and 1 had emission when started in a nonsexual manner. Sexual therapy using squeeze and stop/start techniques was unsuccessful in all cases. Patients were started on phenoxybenzamine, terazosin or prazosin and reported slight improvement. We believe that injury in the conus area of the spinal cord may disinhibit the ejaculatory mechanism and allow for premature emission.

Rescue of acute portal vein thrombosis after liver transplantation using a cavoportal shunt at re-transplantation.

BACKGROUND: Portal vein thrombosis is a rare but devastating complication following orthotopic liver transplantation. Fulminant liver failure ensues with acute portal vein thrombosis after transplantation limiting the treatment options. METHODS: We successfully re-transplanted a 46-year-old female patient who developed acute portal vein thrombosis 19 d after orthotopic liver transplantation. Vascular reconstruction included a cavoportal shunt to augment portal blood flow. RESULTS: Twelve months after re-transplantation this patient lives independently and enjoys excellent liver allograft function. CONCLUSIONS: Cavoportal shunt can augment portal blood flow in adult recipients of orthotopic liver transplants. This technique can be successfully employed during re-transplantation when portal blood flow is inadequate to maintain patency.

Use of ultrasound and cystoscopically guided pancreatic allograft biopsies and transabdominal renal allograft biopsies: safety and efficacy in kidney-pancreas transplant recipients.

The use of allograft biopsies to guide treatment after solid organ transplantation is a valuable tool in the detection and treatment of rejection. Prior development and use of the cystoscopically guided pancreatic allograft biopsy have allowed for more accurate and timely diagnosis of pancreatic allograft dysfunction, possibly contributing to our 1-year pancreas graft, renal allograft and patient survival rates of 87.1%, 88.5% and 96.8%, respectively. We reviewed our experience, examining efficacy and complication rates of pancreas and kidney biopsies in 31 cadaveric pancreas or combined kidney and pancreas transplants performed between June 1990 and February 1992 with at least 1 year of followup. There were 94 pancreas, 54 kidney and 53 duodenal mucosal biopsies in 29 evaluable patients. This biopsy technique uses a 24.5F side-viewing nephroscope to view the cystoduodenostomy, with the duodenum acting as a portal for biopsy needles into the pancreas. Pancreatic tissue is obtained with either an 18 gauge, 500 mm. Menghini aspiration/core needle or an 18 gauge, 500 mm. Roth core needle. Percutaneous renal allograft biopsies are performed independently or simultaneously with the pancreas biopsies using a 16 gauge spring loaded needle. Pancreas biopsies were prompted by clinical indications of rejection (decreased urinary amylase, increased serum amylase or increased serum creatinine) or by protocol (10, 21 and 40 days postoperatively). Among the biopsies 30% were required by protocol, of which 10 (36%) revealed abnormal pathological findings and 5 (18%) showed evidence of occult cellular rejection. Renal biopsies demonstrated rejection in 69% of the cases. Of simultaneous pancreas/kidney biopsies 33% revealed concomitant rejection. A total of 88 Menghini needles with 170 passes was used in 73 biopsy attempts, yielding 126 tissue cores with a 16% complication rate. A total of 41 Roth needles was used with 73 passes in 34 biopsy attempts, yielding 55 tissue cores with a complication rate of 21%. Complications included self-limited bleeding from the biopsy site in 13% of the cases, bleeding requiring clot evacuation and fulguration in 1% and asymptomatic hyperamylasemia in 12%. Renal biopsy complications included 1 arteriovenous fistula (2%). We conclude that ultrasound and cystoscopically guided pancreatic allograft biopsy and percutaneous renal allograft biopsies are safe and essential methods of obtaining tissue for histological diagnosis without serious sequelae. The Menghini and Roth needles in cystoscopically guided pancreatic allograft biopsy have similar yield and complication rates in obtaining pancreatic tissue, although they require different performance techniques. In some cases both needles are necessary and are complementary in obtaining adequate tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Retrospective comparison of the patency of Wallstents and Palmaz long-medium stents used for TIPS. Transjugular intrahepatic portosystemic shunts.

PURPOSE: To compare patency rates of transjugular intrahepatic portosystemic shunts (TIPS) after placement of long-medium Palmaz stents or Wallstents. METHODS: We performed a retrospective review of TIPS performed at our institution between December 1997 and December 1998. During this time period we placed long-medium Palmaz stents for TIPS procedures in 17 patients and Wallstents in 20 patients as the initial stent. Patency was determined on follow-up by ultrasound, angiography, or pathologic examination in the event of transplant. RESULTS: Primary patency in the Palmaz stent group was 70.6% (12/17 patients) (follow-up 1-399 days, mean 127 days). Both primary assisted and secondary patency in the Palmaz group was 100% (17/17 patients) (follow up 1-399 days, mean 154 days). Primary patency in the Wallstent group was 50% (10/20 patients) (follow up 1-370 days, mean 65 days). Primary assisted patency in the Wallstent group was 80% (16/20 patients) (follow up 1-601 days, mean 141 days). Secondary patency in the Wallstent group was 100% (20/20 patients) (follow up 2-601 days, mean 142 days). Kaplan-Meier analysis of the two groups of patients yielded a primary patency of 266 days (standard error 45 days) for TIPS with the Palmaz stent and 139 days (standard error 45 days) for the Wallstent (p =.04). The 3, 6, and 12-month primary patency rates were .84, .63, and .42 respectively for the Palmaz stents and .36, .36, and .18 respectively for the Wallstent. There was no significant difference in primary assisted or secondary patency between the two stent groups. The mean tract curvature in the patients with Palmaz stents was 23.5 degrees (SD 18.2 degrees, range 0-69.0 degrees ) compared with 57 degrees (SD 34.5 degrees, range 7.0-144.0 degrees ) in patients with Wallstents (p =.01). CONCLUSIONS: Our nonprospective, nonrandomized study suggests that TIPS created with the long-medium Palmaz stent have a higher primary patency than those created with the Wallstent in tracts that are relatively straight.

Quantitation of BK virus load in serum for the diagnosis of BK virus-associated nephropathy in renal transplant recipients.

BK virus-associated nephropathy is an increasingly recognized cause of graft dysfunction among kidney transplant recipients, and definitive diagnosis requires renal biopsy. By using a newly developed, quantitative, real-time polymerase chain reaction (PCR) assay for BK virus DNA, a retrospective analysis was done of sequential serum samples (n=28) from 4 transplant recipients with histopathologically documented BK virus nephropathy and from samples (n=76) from 16 transplant recipient control patients. BK virus DNA was detected in serum samples from all 4 case patients versus 0 of 16 control patients (P< .0001, Fisher's exact test) at a median of 32 weeks (range, 17-61 weeks) before the diagnosis of BK virus nephropathy. BK virus load decreased in 3 of 3 patients after the reduction of immunosuppression and/or nephrectomy. It is concluded that quantitative PCR for BK virus DNA in serum is useful both for identifying transplant recipients at risk for BK virus nephropathy and for monitoring the response to therapy.