J M Millis

Incidence and outcome of infection by vancomycin-resistant Enterococcus following orthotopic liver transplantation

Vancomycin-resistant Enterococcus (VRE) has become a significant nosocomial pathogen. For this study, the records of 325 patients who underwent orthotopic liver transplantation (OLT) were reviewed. Thirty-four patients were infected by VRE (incidence of 10.5%, 14% in adults vs. 5% in children, P < 0.01). Common features of patients who developed infections with VRE included previous antibiotic use (25 patients, 15 of whom received vancomycin), co-infection by other pathogens (28 patients), and relaparotomy following OLT (20 patients). Pulmonary and/or renal failure preceded infection by VRE in 11 and 4 adult patients, respectively. Biliary complications were exceedingly common in patients infected by VRE (28 patients) and significantly increased the risk of infection by VRE (21.5% vs. 3.1% for patients without biliary complications, P < 0.0001). Mortality associated with VRE infections was high (56% vs. 19% for patients not infected by VRE, P < 0.0005). The most frequent cause of death was sepsis (16 of 19 patient deaths), often polymicrobial. The high incidence of infection by VRE following OLT, the lack of effective antibiotics for the treatment of VRE, and the association of VRE with patient mortality emphasizes the need to define the risk factors associated with VRE infection. We suggest early surgical intervention to treat complications that may predispose patients to infection by VRE.

Comparison of pancreas transplantation with portal venous and enteric exocrine drainage to the standard technique utilizing bladder drainage of exocrine secretions.

Although bladder drainage of pancreatic exocrine secretions has been reported to decrease morbidity and improve pancreas allograft survival, significant complications remain associated with this technique. Furthermore, this technique requires systemic venous drainage of pancreas allografts. Evidence suggests that portal venous drainage of pancreas grafts prevents hyperinsulinemia and improves lipoprotein composition. This report documents our initial experience with portal venous and enteric exocrine drainage of pancreas allografts (portal/enteric technique) and compares it with the standard technique of systemic venous and bladder exocrine drainage (systemic/bladder technique). Patient and allograft survival, as well as allograft function, were comparable for the two procedures. There were no significant technical complications in this pilot series. Enteric exocrine drainage was associated with a significant reduction in the incidence of acidosis and dehydration when compared with bladder drainage (P<0.005). The portal/enteric technique also avoided reoperation for enteric conversion, as was required by 33% of patients in the systemic/bladder group. The incidence and outcome of allograft rejection were similar for the two techniques. These data suggest that combined pancreas/kidney transplantation with portal venous and enteric exocrine drainage is safe and results in outcomes similar to the standard technique, while eliminating many complications of bladder drainage. These findings should encourage additional studies to determine the consequences of portal venous drainage.

An analysis of hepatic retransplantation in children

BACKGROUND The limited supply of organ donors has led some groups to reconsider the role of retransplantation. Historically, except for children with malignancies, extrahepatic sources of sepsis, or severe irreversible neurologic injuries, our institution has offered all children with failing liver grafts the option of retransplantation regardless of their current severity of illness. The purpose of this study was to examine the outcome of hepatic retransplantation in children in an attempt to identify factors predictive of outcome and to assess the results of our approach to retransplantation. METHODS Between October 1984 and December 1995, 314 children less than 15 years of age underwent a total of 441 liver transplants. Data were obtained retrospectively by review of hospital records. RESULTS With a mean follow-up period of 5.3+/-2.7 years, the overall patient survival rates at 1 and 5 years were 77.1% and 67.1%, respectively. Primary allograft survival rates were 65.6% and 56.5%, respectively. Of the 137 patients who developed failure of their primary allograft, 92 underwent retransplantation (29.3% of all primary transplants). Both patient and allograft survival rates were significantly decreased after retransplantation (P<0.0001 versus primary transplants). Univariate and multivariate analysis of retransplanted patients revealed only two factors that were statistically related to patient and graft survival: age at the time of retransplantation (P<0.02 univariate and P<0.05 multivariate) and retransplantation with a reduced-size allograft (P<0.005 univariate and P<0.05 multivariate). In this series, the effect on patient survival of differences in medical condition as reflected by United Network for Organ Sharing (UNOS) status approached, but did not achieve, significance (P=0.08 for UNOS 1 versus UNOS 2 and 3). UNOS status did not affect graft survival. Neither the cause of primary allograft loss or the timing of retransplantation relative to the first transplant were related to outcome. CONCLUSIONS These data demonstrate that the failure of primary hepatic allografts remains a major problem in pediatric liver transplantation and that the overall results of retransplantation were significantly worse than those associated with primary transplants. We have identified a group of children who experienced a significantly worse outcome after retransplantation. This group consisted of children less than 3 years of age retransplanted using reduced-size grafts. Based on this finding, we now attempt to avoid retransplanting young children with reduced-size grafts. By using this approach, we hope to be able to offer children the option of retransplantation with improved results and simultaneously minimize the negative impact on patients awaiting primary transplants.

Tacrolimus therapy for refractory acute renal allograft rejection : Definition of the histologic response by protocol biopsies

UNLABELLED Protocol biopsies were performed to define the histologic response to tacrolimus therapy in patients with refractory acute renal allograft rejection. Renal allograft biopsies were performed at defined intervals after initiation of tacrolimus therapy. Protocol biopsies were performed before tacrolimus therapy (within 48 hr of initiation of therapy) and after 1 week of therapy. If the 1-week biopsy did not show rejection reversal, repeat protocol biopsies were obtained at 1- to 2-week intervals, until histologic reversal was observed. Additional biopsies were obtained at 4 weeks and at 8-12 weeks after initiation of tacrolimus therapy. Indicated biopsies were also performed to evaluate increases in serum creatinine. A total of 92 biopsies were performed in 23 patients (average 4.0 biopsies/ patient). Biopsies were performed in each patient immediately before starting tacrolimus therapy (23 biopsies), and 69 biopsies (3.0 biopsies/patient) were performed during tacrolimus therapy. Rejection diagnosis was based on strict Banff criteria. Pretacrolimus biopsies demonstrated mild acute rejection in 64% of patients and moderate acute rejection in 36%. One week after initiation of tacrolimus therapy, protocol biopsies revealed the following: no rejection (60%), improvement (13%), no change (20%), and worsening rejection (7%). Histologic changes at 1 week did not correlate with changes in renal function, as 63% of patients that showed histologic improvement or reversal during the first 2 weeks of therapy did not show improvement in serum creatinine. A lack of histologic improvement (or worsening) at 1 week was demonstrated in a significant proportion of patients (27%); increased tacrolimus dosing provided rejection reversal or improvement in 1-2 weeks in each of these patients. Recurrent rejection was diagnosed on eight biopsies in seven patients, however six episodes were diagnosed by protocol biopsies alone (i.e., in the absence of an elevation in serum creatinine). Delayed improvement in renal function, despite histologic reversal, was likely due to physiologic effects of tacrolimus (i.e., afferent arteriolar vasoconstriction), as histologic evidence of tacrolimus toxicity was not observed during the first 2 weeks of therapy. Histologic evidence of tacrolimus nephrotoxicity (nodular arteriolar hyalinosis) was found in 21% (15 of 69) of biopsies in 39% of patients (9 of 23) at a median time of 60 days (range 12-150 days). Tacrolimus dose and blood levels (by IMx assay) did not correlate with development of clinically silent or clinically evident nephrotoxicity. IN CONCLUSION 1) protocol biopsies provide information that allows individualization of tacrolimus rejection therapy, 2) histologic resolution of rejection often precedes biochemical improvement, 3) histologic evidence of tacrolimus nephrotoxicity is seldom observed in the first 2 weeks of therapy, and 4) clinically silent recurrent rejection and clinically silent tacrolimus nephrotoxicity are observed with significant frequency during tacrolimus therapy for refractory renal allograft rejection.

2007: The Year of Regulatory Change

INTRODUCTION The two countries that performed the most organ transplants in 2006, the United States and China, initiated significant regulatory changes in 2007 that continue into 2008 and likely several more years. The purpose of this article is to highlight the reasons behind the regulatory initiatives, document the new regulations, and assess the impact thus far. METHODS Review of US and Chinese governmental regulations emphasizing the underlying principles and impact. RESULTS We evaluated the changes with respect to equity and transparency; understanding transplant policy; field strength; and informed consent. We found a number of similarities between the US and Chinese regulatory changes. The changes in the United States introduced new members into the team (independent donor advocates) and improved documentation, while China began the process of regulation by defining the process and identifying practices that are not allowed. CONCLUSIONS We found a number of similarities between the regulatory changes in the United States and China. Both countries have made significant progress in attempting to improve the process for both donors and recipients. The United States is a more mature system, while China is attempting to move toward an international standard. In the short term, there may be decreased overall access to transplantation while transplant centers and policies adjust to the new regulations in both countries.