Renal Transplantation With Final Allocation Based on the Virtual Crossmatch.

Solid phase immunoassays (SPI) are now routinely used to detect HLA antibodies. However, the flow cytometric crossmatch (FCXM) remains the established method for assessing final donor-recipient compatibility. Since 2005 we have followed a protocol whereby the final allocation decision for renal transplantation is based on SPI (not the FCXM). Here we report long-term graft outcomes for 508 consecutive kidney transplants using this protocol. All recipients were negative for donor-specific antibody by SPI. Primary outcomes are graft survival and incidence of acute rejection within 1 year (AR <1 year) for FCXM+ (n = 54) and FCXM- (n = 454) recipients. Median follow-up is 7.1 years. FCXM+ recipients were significantly different from FCXM- recipients for the following risk factors: living donor (24% vs. 39%, p = 0.03), duration of dialysis (31.0 months vs. 13.5 months, p = 0.008), retransplants (17% vs. 7.3%, p = 0.04), % sensitized (63% vs. 19%, p = 0.001), and PRA >80% (20% vs. 4.8%, p = 0.001). Despite these differences, 5-year actual graft survival rates are 87% and 84%, respectively. AR <1 year occurred in 13% FCXM+ and 12% FCXM- recipients. Crossmatch status was not associated with graft outcomes in any univariate or multivariate model. Renal transplantation can be performed successfully, using SPI as the definitive test for donor-recipient compatibility.

Nesiritide as bridge to multi-organ transplantation: a case report.

Nesiritide, an intravenous form of human B-type natriuretic peptide, has been approved as treatment for patients with acute decompensated heart failure. Due to its action on different receptors, nesiritide has many effects, including vasodilation and natriuresis. Cardiac preload and afterload decrease, leading to an increase in cardiac output through effects on smooth muscle and the kidneys. As a bridge to cardiac transplantation, nesiritide has been used to maintain vasodilation and diuresis without sacrificing kidney function. Our patient, prior to multi-organ transplantation, had a pulmonary capillary wedge pressure of 41 mm Hg on milrinone monotherapy, which decreased slightly with nitroprusside and further decreased to 4 mm Hg after the addition of nesiritide. The patient's measured creatinine clearance level was calculated to be 40 mL/min. When nesiritide therapy was begun, the renal function did not improve, but, as the hemodynamics improved, renal function did not decrease.

Ethical considerations and rationale of adult-to-adult living donor liver transplantation.

Adult-to-adult living donor liver transplantation (ALDLT) is a reality; shortly after its introduction into clinical practice, it is being performed in approximately 50 centers throughout the United States and Europe. The quick development of ALDLT and some deaths among donors repropose old ethical dilemmas and confront the transplant community with new urgent problems. To minimize risks for recipients and, especially, donors, two key questions are addressed: (1) who can or should perform the procedure, and (2) what patient should undergo the procedure. The high risks taken by live donors undergoing a hemihepatectomy seem to be justified by the steadily increasing mortality of adult recipients waiting for transplantation. A comprehensive consent procedure is at the base of responsible decision making for both donors and recipients. In adherence to basic medical criteria, the autonomy of decision of donors and recipients may allow the extension of indications to patients not suitable to undergo transplantation with cadaveric grafts. The broadening of indications is appropriate only in centers with adequate experience and proven expertise in ALDLT. The medical community faces the duty of regulating ALDLT before external influences force undesired policy changes, particularly if not based on medical grounds. Individual centers and patients are ultimately responsible for the correct use of LDLT.

Is any method of vascular control superior in hepatic resection of metastatic cancers? Longmire clamping, pringle maneuver, and total vascular isolation.

HYPOTHESIS: Although control of the hepatic vascular pedicle is commonly used during hepatic resection, the optimal method of vascular control continues to be debated. The utility of total or selective vascular isolation, pedicle inflow occlusion, or the absence of vascular isolation during minor and major hepatectomy needs to be examined. DESIGN: Retrospective review of hepatic resections performed for either isolated colorectal or noncolorectal hepatic metastases. SETTING: The University of Chicago Hospitals, Chicago, Ill, a tertiary-care referral center. PATIENTS: One hundred forty-one patients who underwent hepatic resection for isolated metastatic liver disease were identified through The University of Chicago Hospitals Tumor Registry. MAIN OUTCOME MEASURES: Intraoperative parameters, perioperative morbidity and mortality, and tumor recurrence. RESULTS: Four groups were compared with alternative methods of vascular management, including total vascular isolation, Longmire clamping, Pringle maneuver, or no vascular control. Tumor number and size were not significantly different between groups. Blood loss and transfusion requirements tended to be higher in the total vascular isolation group and were significantly higher compared with the Pringle group (P =.06) and the no vascular control group (P =.04), but this also correlated with a higher incidence of complexity of surgical resection. The highest incidence of postoperative complications occurred in the total vascular isolation group (P<.05). With similar permanent pathologic margins, the rates of intrahepatic recurrence were similar among all groups, with the no vascular control group having the lowest recurrence rate. CONCLUSIONS: All methods of vascular control appeared equivalent with respect to limiting blood loss and transfusion requirements while providing adequate surgical margins. The highest rates of blood requirements and complications were noted in the total vascular isolation group, which corresponded to the highest incidence of complex resections. The Longmire clamp group incurred the lowest incidence of complications and resulted in identical surgical margins. The application of vascular control is beneficial to surgeons during hepatic resection, but the method of control should be selected based on the location and complexity of resection required and preference of the individual surgeon.

Open cardiotomy for removal of migrating transjugular intrahepatic portosystemic shunt stent combined with liver transplantation.

BACKGROUND: Transjugular intrahepatic shunts are widely used for the management of variceal bleeding. Complications such as stent misplacement or migration may occur. METHODS: We describe the management of a transjugular intrahepatic shunts stent that migrated across the tricuspid valve in a patient with Child-Pugh category C cirrhosis. RESULTS: An attempt at percutaneous retrieval of the stent was unsuccessful. Due to the unacceptably high risk for mortality from open heart surgery with cardiopulmonary bypass in the setting of cirrhosis, stent removal was deferred until the time of orthotopic liver transplantation. The procedures were performed successfully, and the patient made a good recovery. CONCLUSION: Surgical stent extraction and valve repair can be performed safely along with orthotopic liver transplantation in carefully selected patients with end-stage liver disease.

Are concerns over right laparoscopic donor nephrectomy unwarranted?

OBJECTIVE: To examine the ability of several large, experienced transplantation centers to perform right-sided laparoscopic donor nephrectomy safely with equivalent long-term renal allograft function. SUMMARY BACKGROUND DATA: Early reports noted a higher incidence of renal vein thrombosis and eventual graft loss. However, exclusion of right-sided donors would deprive a significant proportion of donors a laparoscopically harvested graft. METHODS: A retrospective review was performed among 97 patients from seven centers performing right-sided laparoscopic donor nephrectomy. Surgical and postoperative demographic factors were evaluated. Complications were identified and long-term renal allograft function was compared with historical left-sided laparoscopic donor nephrectomy cohorts. RESULTS: Right laparoscopic donor nephrectomy was performed for varying reasons, including multiple left renal arteries or veins, smaller right kidney, or cystic right renal mass. Mean surgical time was 235.0 +/- 66.7 minutes, with a mean blood loss of 139 +/- 165.8 mL. Conversion was required in three patients secondary to bleeding or anatomical anomalies. Mean warm ischemic time was limited at 238 +/- 112 seconds. Return to diet was achieved on average after 7.5 +/- 2.3 hours, with mean discharge at 54.6 +/- 22.8 hours. Two grafts were lost during the early experience of these centers to renal vein thrombosis. Both surgical and postoperative complications were limited, with few long-term adverse effects. Mean serum creatinine levels were higher than open and left laparoscopic donor nephrectomy on postoperative day 1, but at all remaining intervals the right laparoscopic donors had equivalent creatinine values. CONCLUSIONS: These results confirm that right laparoscopic donor nephrectomy provides similar patient benefits, including early return to diet and discharge. Long-term creatinine values were no higher than in traditional open donor or left laparoscopic donor cohorts. These results establish that early concerns about high thrombosis rates are not supported by a multiinstitutional review of laparoscopic right donor nephrectomies.

Portal and mesenteric venous calcification in patients with advanced cirrhosis.

OBJECTIVE: The incidence of calcification in the portal and mesenteric venous system was studied in patients with advanced cirrhosis undergoing evaluation for liver transplantation. The significance of portal and mesenteric calcification on liver transplantation was also investigated. CONCLUSION: An 11% incidence of portal and mesenteric venous calcification was found in patients with cirrhosis, which was much higher than anticipated. Two (29%) of seven patients who had calcification present on CT and underwent liver transplantation died at surgery as a result of portal venous thrombosis. Thus, venous calcification seen on CT is a significant finding in patients undergoing liver transplantation.

Hepatic resection: effective treatment for primary and secondary tumors.

BACKGROUND: Hepatic resection is an accepted therapeutic modality for isolated colorectal metastases (CRM) and primary hepatobiliary cancers (PC). Controversy continues regarding the safety, efficacy, and appropriateness of resection for noncolorectal metastases (NCM). METHODS: A retrospective review of 167 resections in 160 patients was performed to evaluate the impact of demographics and perioperative data on survival and recurrence. Statistical analyses were performed by Student t test, analysis of variance, and Kaplan-Meier survival estimates. RESULTS: Resections were performed for CRM, 110 of 167 (66%), NCM, 31 of 167 (19%), and PC, 26 of 167 (15%). The interval from primary to metastases was significantly longer in the NCM group than the CRM group (34.7+/-45.1 vs. 18.7+/-23.7 months; P<.01). Mean number of lesions was not different between groups; however, NCM were larger than CRM (5.9+/-4.5 vs 4.5+/-2.9 cm; P<.05). Operative complications were significantly greater for PC (54%) versus CRM and NCM (21% and 19%, respectively; P<.01), although length of stay was similar between groups. Perioperative mortality was 2%. Actuarial survival at 1 year, 3 years, and 5 years was CRM 91%, 54%, and 40%, PC 75%, 60%, and 38%, and NCM 68%, 36%, and not available, respectively (CRM vs. NCM; P<.01 at 3 years). CONCLUSIONS: Hepatic resection for primary and secondary malignancy can be performed with minimal morbidity and mortality. Resection of NCM is associated with a lower overall survival compared with CRM and PC. The disease-free interval from resection of the primary to metastasectomy is prolonged and hepatic recurrence infrequent after resection in the NCM group. These results suggest that tumor biology is a critical determinant of outcome after hepatic resection of primary and secondary hepatic tumors.

Combined liver and kidney transplantation in children.

BACKGROUND: Preexisting renal dysfunction has been reported to significantly increase the morbidity and mortality associated with orthotopic liver transplantation (OLT). OLT alone has been recommended for adults and children with end-stage liver disease and reversible causes of renal failure (i.e., hepatorenal syndrome), whereas combined liver and kidney transplantation (LKT) has been shown to be an effective treatment for adults with combined end-stage liver and kidney disease. The purpose of this study was to examine the role of LKT in children. METHODS: Between October of 1984 and 1997, 385 children less than 18 years of age underwent OLT at the University of Chicago. During this same time period 12 patients underwent LKT. Data were gathered by retrospective review of the patients medical records and by interviews conducted with the patients' families. RESULTS: Actuarial patient survival was comparable for children who underwent OLT alone and LKT (69% versus 67% at 5 years). All allograft losses in the LKT group were the result of patient death and occurred within the first 90 postoperative days. Factors associated with decreased patient survival included severity of illness as reflected by United Network of Organ Sharing status and LKT after failed OLT or cadaveric renal transplant. CONCLUSIONS: In children with concomitant endstage liver and kidney disease, LKT can be considered an effective therapeutic option in selected patients. Long-term patient survival in patients undergoing LKT is comparable to that of patients with normal renal function undergoing OLT alone.

Primary living-donor liver transplantation at the University of Chicago: technical aspects of the first 104 recipients.

OBJECTIVE: To evaluate the impact of technical modifications on living-donor liver transplants in children since their introduction in 1989. SUMMARY BACKGROUND DATA: Although more than 4,000 liver transplants are performed every year in the United States, only approximately 500 are performed in children. Living-donor liver transplantation has helped to alleviate the organ shortage for small children in need of liver transplantation. Few centers have amassed a sufficient number of cases to evaluate the impact of the different techniques used in pediatric living-donor liver transplantation. METHODS: From 1989 through 1997, 104 primary living-donor liver transplants were performed at the University of Chicago. Three phases of the living-donor liver transplant program can be defined based on the techniques of vascular reconstruction: phase 1, November 1989 to November 1994 (n = 78); phase 2, November 1994 to January 1996 (n = 6); and January 1996 to present (n = 20). The patients' charts were reviewed retrospectively. The incidence and type of vascular complications and patient and graft survival rates were analyzed. RESULTS: Although the demographics of the patients have not changed during the three phases of the living-donor liver transplant program, the outcomes have improved. Without the use of conduits, the incidence of portal vein complications has significantly decreased from 44% to 8%. The incidence of hepatic artery thrombosis has decreased from 22% to 0% with the use of microvascular techniques. The combined use of both techniques has led to a significant increase in graft survival, from 74% to 94%. CONCLUSIONS: The living-donor liver transplant recipient operation has undergone significant technical changes since its introduction in 1989. These changes have decreased the vascular complications associated with this type of graft. Avoiding the use of vascular conduits and performing microvascular hepatic artery anastomoses are the critical steps in improving graft survival.

Modern immunosuppression.

The current treatment of posttransplant lymphoproliferative disease (PTLD) includes prophylaxis at the time of transplant, decreasing or stopping immunosuppresion and initiation of antiviral therapy in patients with polymerase chain reaction or clinical evidence of PTLD, and judicial reintroduction of immunosuppression in patients who have cleared their PTLD and have begun to have rejection. The pharmacology, pharmacokinetics, notable side effects, and toxicities of the immunosuppressive agents are described in this article. At the conclusion of each section the author's current practice with these agents and treatment strategies are described.

Indications, evaluations, and postoperative care of the combined liver-heart transplant recipient.

Multiorgan transplantation is now possible because of improvements in immunosuppression and surgical techniques. Combined liver-heart transplantation (CLHT) is a new option with initial 1-year data reporting 80% 1-year survival rates. Organs transplanted with the liver appear to have less allograft rejection. Within the United States, fifteen CLHTs have been performed. Three CLHTs have been performed at the University of Chicago and are discussed in this article. Guidelines for evaluation and listing criteria for CLHT recipients have not been established in the medical community. Postoperative care of this patient group is demanding and requires a thorough understanding of multiorgan pathophysiology, management of high-incidence acute renal dysfunction, tight intravascular volume regulation, and an experienced multidisciplinary approach to care.

Liver transplantation at the University of Chicago.

Since our 1995 report, improvements in patient survival after liver transplantation have widened indications for liver transplantation and led to a greater imbalance between donor supply and need. The organ shortage is the major barrier to liver transplantation at this time. Despite expanded donor criteria, there has been only a marginal increase in the number of liver transplants performed nationally. We have used several approaches to decrease the demand for organs in both adults and children. Our center was one of the first institutions to use reduced-size, living-donor, and split liver transplants routinely. The use of reduced-size liver transplants has decreased as the use of split liver transplantation has increased. Both split liver transplantation and living donor transplantation play an important role in caring for pediatric and adult patients with end-stage and fulminant liver disease. We have concentrated our recent efforts to optimizing the technical aspects of living donor transplantation in order to decrease the need for retransplantation and further organ use. These efforts have dramatically increased graft survival. We have also focused attention on treating patients prior to transplantation in an attempt to eventually abrogate the need for traditional transplantation in some disease processes. With the use of hepatocytes and liver assist devices, we have demonstrated that we can provide a level of metabolic support not achieved with traditional medical therapy for patients with fulminant hepatic failure. As further advances in these therapies are made over the next several years, a concerted effort to bridge patients to recovery will be made. As liver transplantation has become more standardized, it has opened the door to more challenges. We have used liver transplantation in combination with cardiac transplantation to care for selected patients with end stage disease of both organs. This has been remarkably successful for the 3 patients transplanted at the University of Chicago. The immunologic benefit of this combination appears to be a decreased incidence of cardiac rejection. We have standardized the technical components of this combined operation to allow for optimal organ function and patient survival.