Juan D. Arenas

Efficacy and Safety of Low-Dose Valganciclovir in the Prevention of Cytomegalovirus Disease in Adult Liver Transplant Recipients

The efficacy and safety of valganciclovir (VGCV) for cytomegalovirus (CMV) prophylaxis in liver transplant recipients has not been established. We retrospectively compared the efficacy and safety of low‐dose oral VGCV (450 mg once daily for 90 days) and standard oral ganciclovir (1 g three times a day for 90 days, GCV) in preventing CMV disease in 109 adult liver transplant recipients who survived at least 1 month between January 2001 and April 2003 (49 GCV and 60 VGCV). The incidence of CMV disease at 1 year post‐transplant was similar among patients treated with VGCV and GCV (3% and 4%, respectively). Three of the four CMV disease cases occurred in high‐risk recipients with CMV serotype of donor+/recipient− (D+/R−) and all cases presented after completion of CMV prophylaxis, ranging 114‐152 days post‐transplant. Severe neutropenia was rare, and thrombocytopenia and anemia occurred at similar frequencies with both prophylaxis regimens. In conclusion, a 90‐day regimen of low‐dose oral VGCV has a similar efficacy and safety profile to high‐dose oral GCV in adult liver transplant recipients. D+/R− liver transplant recipients remain at risk of developing CMV disease after completion of antiviral prophylaxis. Additional prospective studies with close monitoring for CMV viremia and drug resistance are needed to further establish the optimal dose and duration of VGCV in liver transplant recipients. Liver Transpl 12:112–116, 2006.

Epithelioid hemangioendothelioma of the liver disseminated to the peritoneum treated with liver transplantation and interferon alpha-2B.

Epithelioid hemangioendothelioma (EH) is a rare, low-grade, malignant neoplasm of vascular origin that may develop at different sites, such as in the soft tissue, lungs, or liver. We report the case of a 21-year-old female with primary EH of the liver treated by liver transplantation and review the available literature on EH. This patient developed symptomatic recurrence of the tumor in the pelvis 2 months posttransplant. Treatment with interferon alpha-2b resulted in substantial regression of the pelvic metastases and alleviation of symptoms, but the patient developed graft rejection and died of associated complications 16 months posttransplant. This report is the first showing the efficacy of interferon in this setting.

Gender imbalance in living donor renal transplantation

BACKGROUND Previous studies have shown more women than men among living donors (LD) and more men among recipients of those kidneys. In this study, we compared the evolving demographics of LD transplants. METHODS We retrospectively analyzed all LD transplants performed in our center between 1964 and 2000. RESULTS Among 1182 LD cases, 1035 (88%) were biologically related (LRD) and 147 (12%) were unrelated (LURD). LURD donors and recipients were significantly older than LRD donors and recipients, respectively (P=0.0001). More LURD allograft recipients were male (71%) compared with LRD recipients (57%) (P=0.0013). The proportion of female donors was 55% in both groups. Spousal donations were predominantly wife-to-husband (69%). Compared with the LRD group, there was a greater proportion of female-to-male LURD transplants (46 vs. 30%) and a smaller proportion of female-to-female LURD transplants (10 vs. 25%) (P=0.0001). When spousal pairs were excluded from the analysis, there was a higher proportion of male-to-male (48 vs. 27%) donations and a lower proportion of male-to-female (18 vs. 9%) and female-to-female (25 vs. 17%) transplants in the LURD group (P=0.001). CONCLUSIONS Gender disparities in LD transplantation are primarily due to a higher proportion of wife-to-husband donations and a lower incidence of male-to-female grafts among nonspousal LURD transplants. Strategies should be devised to ensure access for women to renal transplantation and to encourage and facilitate donation by men.

Single-center study of technical graft loss in 714 consecutive renal transplants

No series has specifically focused on rates of technical failure in the kidney transplantation operation. We retrospectively examined the incidence of technical graft loss in a single kidney transplant program. A total of 714 transplants were performed, with a mean follow-up of 3.4 years (range 2–5 years). Technical graft loss was defined as graft loss within the first 2 weeks, without evidence of allograft rejection. Fourteen patients (2%) demonstrated technical graft loss, none of whom received kidneys with multiple renal arteries (n=106 with multiple renal arteries). The incidence of technical graft loss was significantly higher in diabetic recipients (4.3% vs. 1.4%, P=0.03). The mean donor age was significantly higher (46.7 vs. 38.1 years, P=0.05) in patients with technical graft loss. We observed that arterial thrombosis seemed to be related to the donor (older donor significant risk P=0.04) and that venous thrombosis seemed to be related to the recipient (four of seven patients with positive hypercoagulable workup).

Evaluation of pancreatic allograft dysfunction by laparoscopic biopsy.

Background. Histologic evaluation of a failing pancreatic allograft is necessary for accurate classification of graft dysfunction. Unlike percutaneous or transcystoscopic techniques, laparoscopic biopsy allows visualization of the allograft in addition to obtaining tissue for histologic examination. Methods. We retrospectively reviewed all laparoscopic pancreas transplant biopsies performed over a 15-month period ending February 2002. Results. There were 12 laparoscopic pancreas biopsies performed in 11 patients between 6 weeks and 8 years (mean 2.5±2.8 years) after transplant. Indications for biopsy were hyperglycemia (n=8), hyperamylasemia (n=3), and graft tenderness (n=1). Adequate tissue was obtained in 11 of 12 biopsies. Two patients received definitive treatment at the time of laparoscopy (pseudocyst debridement, ovarian cyst excision). Conclusions. Laparoscopic pancreas transplant biopsy allows safe visualization of the allograft and effective specimen retrieval, and in some cases provides the opportunity for therapeutic intervention.

Successful surgical salvage of partial pancreatic allograft thrombosis

BACKGROUND Venous thrombosis remains an important cause of pancreatic graft loss. Nevertheless, reports are scarce of treatment alternatives to complete graft removal. We describe a case of surgical salvage of a partial pancreatic graft thrombosis. METHODS We used descriptive retrospective analysis. RESULTS A 36-year-old patient with juvenile-onset diabetes mellitus and previous living related renal transplant received a cadaveric pancreas transplant in the right iliac fossa with enteric exocrine drainage and standard vascular anastomosis. Two days after discharge from the hospital, he presented with severe right upper quadrant pain, nausea, vomiting, fever, and leukocytosis. He was taken to the operating room for exploration. The tail of the pancreas, which was kinked under the gallbladder, was necrotic and excised. The remainder of the pancreas looked normal. The patient recovered well from surgery and was discharged home 7 days later. CONCLUSIONS Partial pancreatectomy is an acceptable surgical alternative for incomplete graft thrombosis.

Salvage of an unstable brain dead donor with prompt extracorporeal support

Maximizing the support of the marginal donor is an approach to optimizing the donor pool. Thirty-two percent of brain dead donors are hemodynamically unstable and 25% of donors under the age of 60 with traumatic brain injuries expire before organs can be procured (1, 2). When standard donor management protocols are insufficient to salvage a potential donor, aggressive attempts to save the organs can be considered. We present a case of an unstable brain dead donor who suffered premature cardiac death and the use of ECMO (extra-corporeal membrane oxygenation) perfusion in the successful salvage of organs for transplantation. Shortly after being declared brain dead, a 25-year-old patient became hypoxic and hemodynamically unstable. The patient’s family strongly desired organ donation. Despite hormonal replacement and three vasopressors, his mean arterial pressure (MAP) was less than 45 mm Hg. The situation was reviewed with the family, who gave consent for ECMO. The ECMO team was called for an emergent cannulation. The patient was placed on venous-arterial ECMO via cannula placement in the common femoral artery, the internal jugular vein, and the common femoral vein. The patient had a significant improvement in hemodynamics and resumed making urine (MAP 60 to 75). Approximately 75 min later and for unclear reasons, the patient had a cardiac arrest. The MAP was maintained at 53 via ECMO support following cessation of cardiac activity. The patient was transported to the operating room. ECMO flow was not interrupted during this transport. Shortly after arriving into the operating room, cold University of Wisconsin solution was infused through the ECMO circuit. The femoral venous cannula was cut and allowed to drain into a waste bucket. The abdomen was opened and cold slush was poured into the abdominal cavity. The perfusate return soon cleared and the kidneys were procured in the standard fashion. The kidneys were placed on pulsatile pump perfusion. Both kidneys were transplanted and functioned immediately. At our center, we have had success with a protocol using extracorporeal support for NHBDs (non-heart beating donors) (3). In our experience with NHBD, balloon aortic occlusion and a mean ECMO flow of 3.0 L/minute provides physiologic flow to the intra-abdominal organs. Failure of physiologic support to prevent early cardiac death was the second most frequent potentially remediable causes of procurement failure (4). Many potential donors who are unstable are not referred to the local organ procurement organization. In addition, patients who have been hemodynamically tenuous are frequently only kidney donors and the other organs are not procured. In this case, the use of ECMO salvaged the kidneys for donation. In addition, the circuit provided an expeditious means to perfuse with cold University of Wisconsin solution. Using ECMO to optimize brain dead donors is a novel strategy to increase the number of donors and the yield of organs per donor. Michael J. Englesbe Derek Woodrum Meelie Debroy Richard Chenault William Miller Judiann Miskulin Fresca Swaniker John C. Magee Juan D. Arenas Jeffery D. Punch Randall S. Sung Department of Surgery Division of Transplant Surgery and Surgical Critical Care University of Michigan Health System Ann Arbor, Michigan

Erratum: Efficacy and safety of low-dose valganciclovir in the prevention of cytomegalovirus disease in adult liver transplant recipients (Liver Transplantation (2006) vol. 12 (112-116))

2. Flechner SM, Avery RK, Fisher R, Mastroianni BA, Papajcik DA, O’Malley KJ, et al. A randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for cytomegalovirus prophylaxis in high-risk kidney transplant recipients. Transplantation 1998;66:1682–1688. 3. Gane E, Saliba F, Valdecasas GJ, O’Grady J, Pescovitz MD, Lyman S, et al. Randomised trial of efficacy and safety of oral ganciclovir in the prevention of cytomegalovirus disease in liver-transplant recipients. The Oral Ganciclovir International Transplantation Study Group. Lancet 1997; 350:1729–1733. 4. Rubin RH, Kemmerly SA, Conti D, Doran M, Murray BM, Neylan JF, et al. Prevention of primary cytomegalovirus disease in organ transplant recipients with oral ganciclovir or oral acyclovir prophylaxis. Transplant Infect Dis 2000; 2:112–117. 5. Winston DJ, Busuttil RW. Randomized controlled trial of oral ganciclovir versus oral acyclovir after induction with intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in cytomegalovirus-seropositive liver transplant recipients. Transplantation 2003; 75:229–233. 6. Winston DJ, Busuttil RW. Randomized controlled trial of sequential intravenous and oral ganciclovir versus prolonged intravenous ganciclovir for long-term prophylaxis of cytomegalovirus disease in high-risk cytomegalovirus-seronegative liver transplant recipients with cytomegalovirus-seropositive donors. Transplantation 2004;77:305–308.