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Liver transplantation (LT) for hepatocellular carcinoma is effective for selected patients. LT for other malignancies like cholangiocarcinoma (CCA), hepatoblastoma (HB), hepatic epithelioid hemangioepithelioma (HEHE), angiosarcoma (AS), and neuroendocrine tumors (NET) is being defined. For CCA, series that did not emphasize highly selected early stage disease and neoadjuvant or adjuvant chemoradiation had an average 5-year survival of 10%. However, emphasizing neoadjuvant radiation and chemosensitization in operatively confirmed stage I or II hilar CCA has led to improved 5-year survival, up to 82%. LT is indicated under strict research protocols at selected centers, for patients with early stage CCA and anatomically unresectable (Bismuth type IV) lesions. HB is typically sensitive to cisplatin-based chemotherapy. LT plays a role as primary surgical therapy for those individuals in whom tumors remain unresectable after chemotherapy or as rescue therapy for those who are incompletely resected, recur after resection, or develop hepatic insufficiency after chemotherapy and/or resection. Long-term survival is reported at 58-88%. HEHE is a multifocal tumor that lies somewhere between benign hemangiomas and malignant AS. The extensive multifocal nature makes resection difficult and LT an attractive option. Series on LT for HEHE report overall survival of 71-78% at 5 years. However, AS is an aggressive tumor and LT is contraindicated. For NET, resection of the primary tumor and all gross metastatic disease is reported to provide 5-year survival of 70-85%. LT has been employed for some patients for unresectable tumors or for palliation of medically uncontrollable symptoms with 5-year survival reported between 36% and 80%.

Introduction: Due to the scarcity of cadaveric livers, clinical judgment must be used to avoid futile transplants. However, the accuracy of human judgment for predicting outcomes following liver transplantation is unknown. The study aim was to assess expert clinicians' ability to predict graft survival and to compare their performance to published survival models., Materials and Methods: Pre-transplant case summaries were prepared based on 16 actual, randomly selected liver transplants. Clinicians specializing in the care of liver transplant patients were invited to assess the likelihood of 90-day graft survival for each case using (1) a 4-point Likert scale ranging from poor to excellent, and (2) a visual analog scale denoting the probability of survival. Four published models were also used to predict survival for the 16 cases. RESULTS. Completed instruments were received from 50 clinicians. Prognostic estimates on the two scales were highly correlated (median r=0.88). Individual clinicians' predictive ability was 0.61+/-0.13, by area under the receiver operating characteristic curve. The performance of published models was MELD 0.59, Desai 0.66, Ghobrial 0.61, and Thuluvath 0.45. For three cases, clinicians consistently overestimated the probability of survival (87+/-10%, 89+/-9%, 86+/-9%); these patients had early graft failures caused by postoperative complications. DISCUSSION. Clinicians varied in their ability to predict survival for a set of pre-transplant scenarios, but performed similarly to published models. When clinicians overestimated the chance of transplant success, either sepsis or hepatic artery thrombosis was involved; such events may be hard to predict before surgery.

Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. In high-risk populations, including those with hepatitis B or C or with cirrhosis, serum alpha-fetoprotein (AFP) and screening ultrasound have improved detection of resectable HCC. Treatment options, including surgical resection, for patients with HCC must be selected based on the number and size of hepatic tumors, underlying hepatic function, patient condition, and available resources. An approach, which has been summarized shows the corresponding treatment choices under given clinical circumstances. For cirrhotic patients with less than three tumor nodules of a size less than 3 cm or a solitary HCC less than 5 cm, liver transplantation offers long-term survival similar to that observed in patients transplanted for nonmalignant disease. Ablative treatment using either chemical or thermal techniques provides locally effective tumor destruction. Transcatheter arterial chemoembolization (TACE) is commonly used for palliation of unresectable tumors as well as an adjunct to surgical resection, treatment of tumors before transplant, and in conjunction with other ablative therapies in a multimodality approach. Regional approaches to chemotherapy have produced more encouraging results than systemic chemotherapy, although both remain ineffective for long-term tumor control. Several newer treatment modalities are under investigation, including gene therapy, tagged antibodies, isolated perfusion, and novel radiotherapy techniques.

The purpose of this study was to assess regional variability in access to pediatric liver transplantation. The study population included all pediatric patients (age less than 18 years) listed for liver transplantation in the United Network for Organ Sharing (UNOS) database between 1988 and 2004. The effect of region on waiting list survival, the proportion of patients transplanted, and the proportion of patients remaining on the list was determined using Kaplan-Meier and Cox proportional hazard methods. The proportion of technical variant grafts used was compared between regions using chi-square analysis. Kaplan-Meier analyses showed significant effects of region on survival on the waiting list, transplantation, and remaining on the list (all log-rank P < 0.001). Cox proportional hazard models demonstrated that region, urgency status, and listing period exerted independent effects on survival on the waiting list, transplantation, and remaining on the list (all model P < 0.01). Regional variation existed with regard to donor type (P < 0.001). Similar to adults, pediatric survival on the waiting list, the proportion of patients transplanted, and the proportion of patients remaining on the waiting list vary considerably within the 11 U.S. regions. Organ procurement organization specific effects and regional differences in utilization of deceased donor split and living donor organs may contribute to this variability.

CPOE systems hold the promise of both reducing medical errors and improving compliance with evidence-based guidelines. Evidence-based order sets have been used to make evidence-based guidelines actionable at the point of care. Investigators have conducted research into factors effecting order set use, but little has been documented regarding order set compliance. Under the direction of the Chief Medical Officer, Vanderbilt University Medical Center undertook a major effort to ensure order sets in the Vanderbilt CPOE system are evidence-based. The Vanderbilt EvidenceWeb was developed in order to monitor use and progress, and to provide feedback to clinical teams based on their requests for data. Monitoring tools and feedback to clinical groups regarding order set use and compliance have proved to be key components in improving delivery of evidence-based care.

Hypothesis: Living donor liver transplantation (LDLT) results in improved survival compared with deceased whole and split organ transplantation in children., Objective: To evaluate the effect of LDLT on graft and patient survival in pediatric liver transplantation., Design: Retrospective cohort., Methods: Data included all pediatric recipients (aged <18 years) registered in the UNOS (United Network for Organ Sharing) database from October 1, 1987, to May 24, 2004. Covariates predictive of survival by univariate analyses were included in the Cox proportional hazards regression models in a blockwise fashion to determine predictors of survival., Results: Kaplan-Meier graft and patient survival rates were improved in LDLT recipients compared with recipients of deceased whole and split organ transplantations (P<.01). In the initial model (model P<.001), prognostic factors for graft and patient survival included recipient age, race, origin of liver disease, certain pretransplantation laboratory data, medical condition, multiorgan transplantation, retransplantation, recipient-donor ABO blood compatibility, and cold and warm ischemia times. The addition of graft type to the initial covariate set did not significantly change the model (P = .21, covariate P = .09). However, most of the positive prognostic factors identified in the model were inherent characteristics of LDLT recipients and the LDLT procedure., Conclusions: Graft and patient survival in the pediatric population is better with LDLT than deceased organ transplantation. Factors that contribute to this difference include recipients who are less ill, who have shorter cold and warm ischemia times, and those with a decreased need for retransplantation but not the type of graft per se.

With nearly two years of data available since the inception of the MELD and PELD allocation system, this article examines national OPTN/SRTR data to describe trends in waiting list composition, waiting list mortality, transplant rates, and patient and graft outcomes for liver transplantation. Following a 6% reduction in the size of the waiting list after MELD was implemented in 2002, the number of patients on the waiting list grew by 2% from 2002 to 2003, while the number of liver transplants increased by 6%. The overall death rate while on the liver waiting list has decreased from 225 deaths per 1,000 patient years in 1994 to 124 deaths in 2003. As with the waiting list death rates, post-transplant death rates have also decreased over the past decade. Unadjusted one-year patient survival was lower for older donor age groups (88% for donors aged 18-34, 87% for donors aged 35-49, 85% for donors aged 50-64); a similar trend was observed at three and five years following transplantation. Intestine transplantation is performed with slowly increasing frequency and success. Early graft losses and rejection rates have changed little since 1994, but rejection is easier to control and long-term survival is improving.

Hypothesis: Donor, technical, and recipient risk factors cumulatively impact survival and health-related quality of life after liver transplantation., Design: Retrospective study., Setting: Tertiary care center., Patients: A total of 483 adults undergoing primary orthotopic liver transplantation between January 1, 1991, and July 31, 2003., Main Outcome Measures: Graft and patient survival, Karnofsky functional performance scores, Medical Outcomes Study Short Form 36 Health Survey scores, and Psychosocial Adjustment to Illness Scale scores as influenced by potential risk factors including donor age, weight, warm ischemia time, cold ischemia time (CIT), sex, United Network for Organ Sharing (UNOS) status (1 or 2A vs 2B or 3), recipient age and disease, bilirubin level, and creatinine level., Results: Five-year graft survival was 72% for recipients of donors younger than 60 years and 35% for recipients of donors 60 years and older (P<.001). A CIT of 12 hours or more was associated with shorter 5-year graft survival (71% vs 58%; P = .004). Five-year graft survival for UNOS status 2B or 3 was 71% vs 60% for status 1 or 2A (P = .02). A comparable pattern was seen for patient survival in relation to donor age (P = .003), CIT (P = .005), and urgency status (P = .03). Urgent UNOS status, advanced donor age, and prolonged CIT were independently associated with shorter graft and patient survival (P<.05). Functional performance and health-related quality of life were not affected by donor, recipient, or technical characteristics., Conclusions: Combining advanced donor age, urgent status, and prolonged CIT adversely affects graft and patient survival, and the cumulative effects of these risk factors can be modeled to predict posttransplant survival.

Mitochondrial Ca2+ (mCa2+) handling is an important regulator of liver cell function that controls events ranging from cellular respiration and signal transduction to apoptosis. Cytosolic Ca2+ enters mitochondria through the ruthenium red-sensitive mCa2+ uniporter, but the mechanisms governing uniporter activity are unknown. Activation of many Ca2+ channels in the cell membrane requires PLC. This activation commonly occurs through phosphitidylinositol-4,5-biphosphate (PIP2) hydrolysis and the production of the second messengers inositol 1,4,5-trisphosphate [I(1,4,5)P3] and 1,2-diacylglycerol (DAG). PIP2 was recently identified in mitochondria. We hypothesized that PLC exists in liver mitochondria and regulates mCa2+ uptake through the uniporter. Western blot analysis with anti-PLC antibodies demonstrated the presence of PLC-delta1 in pure preparations of mitochondrial membranes isolated from rat liver. In addition, the selective PLC inhibitor U-73122 dose-dependently blocked mCa2+ uptake when whole mitochondria were incubated at 37 degrees C with 45Ca2+. Increasing extra mCa2+ concentration significantly stimulated mCa2+ uptake, and U-73122 inhibited this effect. Spermine, a uniporter agonist, significantly increased mCa2+ uptake, whereas U-73122 dose-dependently blocked this effect. The inactive analog of U-73122, U-73343, did not affect mCa2+ uptake in any experimental condition. Membrane-permeable I(1,4,5)P3 receptor antagonists 2-aminoethoxydiphenylborate and xestospongin C also inhibited mCa2+ uptake. Although extra mitochondrial I(1,4,5)P3 had no effect on mCa2+ uptake, membrane-permeable DAG analogs 1-oleoyl-2-acetyl-sn-glycerol and DAG-lactone, which inhibit PLC activity, dose-dependently inhibited mCa2+ uptake. These data indicate that PLC-delta1 exists in liver mitochondria and is involved in regulating mCa2+ uptake through the uniporter.

Radiofrequency ablation (RFA) is an evolving technology used to treat unresectable liver tumors. Currently, there is no accurate method to determine RFA margins in real-time during the procedure. We hypothesized that a fiber-optic based spectroscopic monitoring system could detect thermal damage from RFA in real-time. Fluorescence (F) and diffuse reflectance (Rd) spectra were continuously acquired from within the expected ablation zone during canine hepatic RFA using a fiber-optic microinterrogation probe (MIP). The F and Rd spectral feedback were continuously monitored and ablations were stopped based on changes in spectra alone. After each ablation, the MIP tract was marked with India ink and the ablation zone was excised. The relationship of the MIP to the zone of ablation was examined grossly and microscopically. F and Rd spectral changes occurred in three characteristic phases as the ablation zone progresses past the MIP. Phase 1 indicates minimal deviation from normal lives. Phase 2 occurs as the MIP lies within the hemorrhagic zone of the ablated tissue. Phase 3 correlates with complete tissue coagulation. The absolute magnitude of spectral change correlates with the gross and histologic degree of thermal damage. Optical spectroscopy is a technology that allows real-time detection of thermal tissue damage. In this study, both F and Rd spectroscopy accurately defined the advancing hemorrhagic edge of the zone of ablation and the central coagulation zone. These results suggest that F and Rd spectroscopy can be used to create a real-time feedback system to accurately define RFA margins.

Hypothesis: Long-term quality of life (QOL) in patients undergoing laparoscopic cholecystectomy (LC) incurring bile duct injury (BDI) and repair is comparable to that of patients undergoing uncomplicated LC., Design: Case comparison study., Setting: Secondary and tertiary care centers., Patients: Eighty-six patients incurring BDI during LC between January 1, 1991, and July 31, 2003, were surveyed. Comparison subjects underwent uncomplicated LC during the same period., Main Outcome Measures: Health-related QOL as assessed by the Karnofsky Performance Scale, Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and Psychosocial Adjustment to Illness Scale., Results: Fifty patients with BDI (39 [78%] female; mean +/- SEM age, 55 +/- 2 years) and 74 patients with uncomplicated LC (51 [69%] female, mean +/- SEM age, 52 +/- 2 years) responded. Of the 50 BDI patients, 48 (96%) had no stricture and normal liver function at QOL assessment. The mean +/- SEM follow-up period to QOL assessment for the BDI and uncomplicated LC groups was 62 +/- 6 and 47 +/- 3 months, respectively. The mean +/- SD Karnofsky Performance Scale scores were 77 +/- 9 vs 93 +/- 8 for the 2 groups, respectively (P <.001). The mean +/- SD SF-36 physical component scale scores after BDI vs uncomplicated LC were 36 +/- 11 vs 47 +/- 12, respectively (P <.001), compared with 50 +/- 10 for the normal population (P <.001). The mean +/- SD SF-36 mental component scale scores were 43 +/- 14 vs 49 +/- 11 for the 2 groups, respectively (P =.02), compared with 50 +/- 10 for the normal population (P =.01). Patients with BDI scored poorer on the Psychosocial Adjustment to Illness Scale health care orientation and domestic environment scales (P=.01)., Conclusion: After BDI and repair, there are long-term detrimental effects of BDI on health-related QOL.

Mitochondrial calcium (mCa + 2) overload occurs during cold preservation and is an integral part of mitochondrial-dependent apoptotic pathways. We investigated the role of mCa + 2 overload in cell death following hypothermic storage using HepG2 cells stored in normoxic-hypothermic (4 degrees C) or hypoxic (< 0.1% O2)-hypothermic Belzer storage solution. Cells were stored for 6 h, with or without 10 microM ruthenium red (mCa + 2 uniporter inhibitor) followed by rewarming in oxygenated media at 37 degrees C. Cytoplasmic cytochrome c levels were studied by Western analysis and by fluorescent microscopy after transfection of cytochrome c-GFP expression plasmid. Immunofluorescence determined the intracellular, spatio-temporal distribution of Bax, and TUNEL staining was used to evaluate cell death after 180 min of rewarming. Caspase activation was evaluated using Western analysis and a caspase 3 activity assay. Bax translocation, cytochrome c release, and early rewarming cell death occurred following hypothermic storage and were exacerbated by hypoxia. Caspase 3 activation did not occur following hypothermic storage. Blockade of mCa + 2 uptake prevented Bax translocation, cytochrome c release, and early rewarming cell death. These studies demonstrate that mCa + 2 uptake during hypothermic storage, both hypoxic and normoxic, contributes to early rewarming apoptosis by triggering Bax translocation to mitochondria and cytochrome c release.

Because most patients with pancreatic cancer present with biliary obstruction, percutaneous transhepatic cholangiopancreatography (PTC) or endoscopic retrograde cholangiopancreatography (ERCP) is often performed first to relieve obstruction. Fine needle biopsy (FNA) provides a tissue diagnosis, but is often nondiagnostic due to sampling error. Computed tomography (CT) is the workhorse of oncology, but is poor at defining the nature of pancreatic lesions. Small primary tumors are often not visualized. Fast magnetic resonance imaging (MRI) techniques allowing dynamic imaging after IV gadolinium and new contrast agents allow better characterization of the lesions for patients having contraindications for IV CT contrast agents. Magnetic resonance cholangiopancreatography (MRCP) allows noninvasive visualization of the biliary tree. Endoscopic ultrasonography (EUS) allows evaluation of the detailed regional anatomy with the possibility of FNA. 18F-Fluorodeoxyglucose (FDG) is the most common tracer used in positron emission tomography (PET), and most malignant tumors, including pancreatic carcinoma, have increased FDG uptake compared with normal cells. This functional imaging does not replace but is complementary to morphological imaging. FDG PET is particularly helpful: (1) for the diagnosis in patients with suspected pancreatic cancer in whom CT fails to identify a mass, or those in whom FNAs are nondiagnostic; (2) for staging by detecting CT-occult metastases; (3) for detecting recurrence; and (4) for monitoring therapy. Limitations include false-positive inflammatory processes and false-negative carcinoma in patients with diabetes and hyperglycemia, and islet cell tumors.

Purpose: The psychometric properties of generic health-related quality of life (HRQOL) assessment instruments were evaluated to identify a reliable, valid, and non-redundant battery to measure longitudinal outcomes in organ transplant patients., Methods: Objective functional performance and subjective HRQOL were assessed in 371 solid organ (liver, heart, kidney, lung) transplant patients using the Karnofsky scale, the SF-36 Health Survey (SF-36), and Psychosocial Adjustment to Illness Scale (PAIS). The surveys' internal-consistency reliability, criterion-related validity, and redundancy were tested., Results: The SF-36 mental (MCS) and physical components (PCS), and PAIS summary scales were internally consistent (all alpha > or = 0.83). Four out of seven PAIS scales (vocational, domestic, sexual, social) were collectively associated with the PCS (R = 0.65, P < 0.001), as was functional performance (r = 0.52, P < 0.001). Three PAIS scales (family, social, psychological distress) were associated with the MCS (R = 0.72, P < 0.001). Only the PAIS healthcare orientation (satisfaction) scale was not associated with the SF-36((R)). The relationship between functional performance and the PCS is stronger (r = 0.52, P < 0.001) than with the MCS (r = 0.25, P < 0.001) and the PAIS global score (r = 0.37, P < 0.001)., Conclusions: The SF-36 and PAIS are internally consistent and exhibit divergent criterion-related validity but, with the exception of the PAIS healthcare orientation scale, are statistically redundant. The advantages of the SF-36 include wider use, more norms, and a lesser response burden. A transplant-specific patient satisfaction inventory was indicated and was developed.

Our goal was to evaluate fluorodeoxyglucose (FDG) positron emission tomography (PET) in staging patients with biliary tract cancers. Fifty consecutive patients who underwent FDG-PET for suspected cholangiocarcinoma (n=36) or gallbladder carcinoma (n=14) were reviewed. Patients with cholangiocarcinoma were divided into two groups: group 1 had nodular type (mass=1 cm) (n=22) and group 2 had infiltrating type (n=14) cholangiocarcinoma. Thirty-one of 36 patients evaluated for cholangiocarcinoma had cholangiocarcinoma and five did not. Sensitivity was 85% for nodular morphology but only 18% for infiltrating morphology. Sensitivity for metastases was 65% but false negative for carcinomatosis in three of three patients. One false positive result occurred in a patient with primary sclerosing cholangitis who had acute cholangitis. Seven (58%) of 12 patients had FDG uptake along the tract of a biliary stent. FDG-PET led to a change in surgical management in 30% (11 of 36) of patients evaluated for cholangiocarcinoma because of detection of unsuspected metastases. Eleven of 14 patients with gallbladder carcinoma were newly diagnosed by cholecystectomy or another type of exploratory procedure, whereas three patients were undergoing follow-up. Nine had residual gallbladder carcinoma at the time of PET. Sensitivity for gallbladder carcinoma was 78%. Sensitivity for extrahepatic metastases was 50% in eight patients; six of them had carcinomatosis. These data suggest that PET is accurate in predicting the presence of nodular cholangiocarcinoma (mass>1cm) but was not helpful for the infiltrating type. PET was also helpful for detecting residual gallbladder carcinoma following cholecystectomy, but was not helpful in patients with carcinomatosis. Although FDG-PET led to a change in management in 30% of patients with cholangiocarcinoma, it must be interpreted with caution in patients with primary sclerosing cholangitis and with stents in place, as well as in those with known granulomatous disease.

Cholangiocarcinoma presents a formidable diagnostic and treatment challenge. The majority of patients present with unresectable disease and have a survival of less than 12 months following diagnosis. Progress has been made by the appropriate selection of patients for treatment options including resection, with the routine use of more aggressive resections in order to achieve margin-negative resections. This has resulted in longer survival times for these patients. Neoadjuvant and adjuvant therapies have, for the most part, not improved survival in patients with this tumor, and new strategies are needed to improve this line of therapy. The prognosis for unresectable patients is poor, and palliative measures should be aimed at increasing quality of life first and increasing survival second.

Background: Primary hepatic carcinoid tumors (PHCTs) are extremely rare, and fewer than 50 cases have been reported in the English-language literature. We report a patient with a PHCT and review the cases in the literature., Methods: Our patient presented with symptoms and underwent liver resection for PHCT and regional lymph node metastasis. He underwent two more liver resections over the following 7 years for recurrent PHCT. Cases reported in the English-language literature were reviewed and survival analysis was performed with the Kaplan-Meier method. The survival impacts of age, gender, tumor foci, extrahepatic metastasis, unilobar versus bilobar disease, and type of preoperative treatment were determined by means of log-rank test., Results: Our patient has been free of symptoms for 14 years of follow-up and free of disease for 8 years of follow-up. Forty-eight cases of PHCT were found in the literature, and 92% of these patients underwent resection. Actuarial 5- and 10-year survival for all patients was 78% and 59%, respectively, whereas for resected patients, 10-year survival was 68%. The administration of preoperative chemotherapy, radiation therapy, or chemoembolization did not impact survival, nor did age, gender, presence of extrahepatic metastasis, number of tumors, or distribution of the tumor within the liver., Conclusions: Resection is the treatment of choice for PHCT and has provided favorable outcomes. Resection for PHCT can be performed in most patients and offers long-term survival.

Background: The current study was undertaken to identify factors specific to kidney transplantation that are associated with posttransplant functional performance (FP) and health-related quality of life (HRQOL)., Methods: Karnofsky FP status was assessed longitudinally in 86 adult kidney transplant recipients. Patients reported HRQOL using the Short Form-36 (SF-36) health survey and the Psychosocial Adjustment to Illness Scale (PAIS)., Results: FP improved (P <0.001) after kidney transplantation (from 75 +/- 1 to 77 +/- 1, 81 +/- 1, and 82 +/- 1 at 0, 3, 6, and 12 months, respectively). Patients receiving organs from living donors showed continued improvement through posttransplant year 1 while those receiving cadaveric organs stabilized at month 6 (simple interaction contrast, year 1 versus pretransplant; P <0.05). Patients receiving dialysis therapy for 6 months or more prior to transplantation demonstrated lower SF-36 posttransplant physical component scores in comparison with patients who were transplanted preemptively (38 +/- 1 versus 45 +/- 2, P <0.05). Path analysis demonstrated the positive direct effect of time on FP with kidney transplantation (beta = 0.23, P <0.05), and the negative direct effects on FP of diabetes (beta = -0.22) and cadaveric organs (beta = -0.22, both P <0.05). In turn, FP had a positive direct effect on HRQOL (beta = 0.40, P <0.001)., Conclusions: Overall improvement in FP is attenuated 1 year after kidney transplantation in recipients of organs from cadaveric donors. The positive effect of time after transplantation, and the negative effects of cadaveric organs and diabetes on posttransplant HRQOL, are indirect and are mediated by the direct effects of these variables on posttransplant FP.

Background: Some previous studies suggested that transplantation performed in Department of Veterans Affairs (VA) patients was associated with a higher rate of complications and poorer outcomes. We examined more than a decade of experience with solid organ transplantation at a single center and compared VA patients with nonveteran patients to assess long-term patient and graft survival and health-related quality of life (HRQOL)., Methods: Demographic, clinical, and survival data were extracted from a database that included all transplants from January 1990 through December 2002 at Vanderbilt University Medical Center (non-VA) and the Nashville VA Medical Center (VA). The HRQOL was assessed in a subset of patients using the Karnofsky functional performance (FP) index and the Short-Form-36 self-report questionnaire. Data were analyzed by Kaplan-Meier survival and analysis of variance methods., Results: One thousand eight hundred nine adult patients receiving solid organ transplants (1,896 grafts) between 1990 and 2002 were reviewed: 380 VA patients (141 liver, 54 heart, 183 kidney, 2 lung) and 1429 non-VA patients (280 liver, 246 heart, 749 kidney, 154 lung). Mean follow-up time was 46 +/- 1 months. Five-year graft survival for VA and non-VA patients, respectively, was liver 65% +/- 5% versus 69% +/- 3% (P = 0.97); heart 73% +/- 8% versus 73% +/- 3% (P = 0.67); and kidney 76% +/- 5% versus 77% +/- 2% (P = 0.84). Five-year patient survival was liver 75% +/- 5% versus 78% +/- 3% (P = 0.94); heart 73% +/- 8% versus 74% +/- 3% (P = 0.75); and kidney 84% +/- 4% versus 87% +/- 2% (P = 0.21) for VA and non-VA, respectively. In the first 3 years after transplant, the FP scores for VA versus non-VA patients were 85 +/- 2 versus 87 +/- 1 (P = 0.50). The SF-36 mental component scales were 47 +/- 3 versus 49 +/- 1 (P = 0.39); and the SF-36 physical component scales were 37 +/- 2 versus 38 +/- 1 (P = 0.59), respectively. Longer-term (through year 7) HRQOL scores for VA versus non-VA patients were FP 85 +/- 1 versus 88 +/- 1 (P = 0.17); mental component scales 47 +/- 2 versus 49 +/- 1 (P = 0.29); and physical component scales 35 +/- 2 versus 39 +/- 1 (P = 0.05), respectively., Conclusions: The veteran patients have similar graft and patient survival as the nonveteran patients. Overall quality of life is similar between veterans and nonveterans during the first three years after transplantation. A trend toward a later decline in the veterans' perception of their physical functioning may stem from the increased prevalence of hepatitis C virus among VA liver transplant recipients, a known factor reducing late HRQOL.

Background: Graft dysfunction as a result of preservation injury remains a major clinical problem in liver transplantation. This is related in part to accumulation of mitochondrial calcium (Ca(2+)), which has been linked to activation of proapoptotic factors. We hypothesized that cold ischemia increases mitochondrial Ca(2+) uptake in a concentration dependent fashion and that ruthenium red (RR) will attenuate these changes by inhibiting the mitochondrial Ca(2+) uniporter., Methods: Rat livers perfused with cold University of Wisconsin (UW) solution (4 degrees C) with or without RR (10 microM) via the portal vein (n = 3 per group) were processed immediately (no ischemia) or after 24 h cold-storage (24 h cold ischemia). Mitochondria were separated by differential centrifugation, and adenosine triphosphate (ATP)-dependent (45)Ca(2+) uptake was determined in the presence of ATP (5 mM), adenosine diphosphate (ADP), or adenosine 5'-beta,gamma-imidotriphosphate (AMP-PNP); variable concentrations of extramitochondrial (45)Ca(2+) were used. All measurements were performed in triplicate. Student's t test with P < 0.05 was taken as significant., Results: Our data demonstrate the following: 1) ATP-dependent (45)Ca(2+) uptake in mitochondria separated from livers following 24 h of cold ischemia in UW alone was higher than in mitochondria isolated from non-ischemic livers; the increased uptake was dependent on the concentration of (45)Ca(2+) in the incubation buffer. 2) There was no difference in ATP-dependent (45)Ca(2+) uptake between nonischemic mitochondria and those separated from livers stored in UW-RR for 24 h. 3) (45)Ca(2+) uptake in mitochondria from livers subjected to 24 h of cold ischemia in UW-RR was significantly lower compared to those from livers stored in UW alone when (45)Ca(2+) concentrations were greater than 1 microM., Conclusion: 1) Cold ischemia affects mitochondrial Ca(2+) handling, especially when it is challenged by high extramitochondrial Ca(2+) concentrations. 2) The addition of RR in preservation solution attenuates the effects of cold ischemia on mitochondrial Ca(2+) handling. 3) Inhibition of mitochondrial Ca(2+) uniporter with RR protects mitochondria from Ca(2+) overload at high Ca(2+) concentrations. These findings may offer a potentially effective strategy for prevention of ischemia-reperfusion injury in liver transplantation.

Our aim was to examine the effects of hepatitis C virus (HCV) infection, a leading cause of end-stage liver disease, and its recurrence after liver transplantation on functional performance and health-related quality of life. Functional performance, liver function, and HCV recurrence were assessed longitudinally in 75 adult transplant recipients (28 with HCV). Quality of life was reported once after transplantation. Functional performance improved through year 2 (P < 0.001) and then declined in those with HCV, whereas the others remained stable (P = 0.05). Time had a positive effect (beta = 0.22, P = 0.05) and HCV infection had a negative effect (beta = -0.28, P = 0.01) on post-transplant functional performance. Educational level (beta = 0.24, P < 0.05) and recent functional performance (beta = 0.31, P = 0.01) had positive effects on quality of life. HCV recurrence was associated with relatively poorer pretransplant functional performance, a greater rate of improvement through month 3 (P < 0.05), and abnormal transaminase values between years 1 and 2 (P < 0.001). Rehospitalization for recurrent HCV was associated with reduced functional performance (P < 0.05). Functional performance improves with time following liver transplantation, but HCV infection exerts an opposing and comparably strong effect. Post-transplant functional performance, in turn, directly affects post-transplant quality of life. Severe, recurrent HCV illness is associated with reduced functional performance.