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Biomedical subjects

Richard B Freeman

Publications and source records attributed to Richard B Freeman.

At least 19 recordsLinked to original sources
PubMed2006

Optimizing staging for hepatocellular carcinoma before liver transplantation: A retrospective analysis of the UNOS/OPTN database.

Assignment of liver allocation priority for hepatocellular carcinoma is predicated on accurate imaging staging. We analyzed radiographically defined stage (radiologic stage [RS]) at listing and most recent extension and pathologic stage (PS) data from 789 liver transplant recipients for whom no pretransplant ablative treatment was given. There were no predetermined imaging or pathological protocols in this retrospective analysis of wait list data. Seventy-two (9.1%), 690 (87.5%), and 27 (3.4%) were listed as stage 1, 2 and >2, respectively. Computed tomography (CT) scan alone (46.4%), magnetic resonance image scan alone (37.1%), ultrasound alone (1.3%), and multiple imaging studies (15.2%) were used with no difference in time to transplant for listing or most recent scan among the recipient groups. Overall accuracy (RS = PS) was 44.1% and was not different if original listing RS or most recent RS was used for comparison with PS. No one type of imaging technique had superior accuracy (P = 0.13); however, CT scan used alone or in combination compared to not being used at all, had higher odds of being accurate (odds ratio [OR] 1.38 [1.03-1.84], P = 0.031). In addition, imaging done less than 90 days before transplant had higher odds of being accurate (OR 1.49 [1.06-2.08], P = 0.019) as did RS = 2 or 3 (OR 5.56 [2.70-11.11], P < 0.0001). We observed considerable variation in RS accuracy among the United Network for Organ Sharing and Organ Procurement and Transplantation Network regions that is unexplained. In conclusion, current imaging requirements for RS prior to liver transplantation are unacceptably inaccurate. Future policy should require more accurate modalities or combinations of techniques.

Carcinoma, Hepatocellular↗
PubMed2006

Transplantation for hepatocellular carcinoma: The Milan criteria and beyond.

KEY CONCEPTS: 1. Liver transplantation offers excellent results for selected candidates with hepatocellular carcinoma (HCC). 2. Selection strategies have evolved but are mainly based on size and number of tumors, which are surrogates for vascular invasion. Newer techniques show promise for identifying patients at high risk for recurrence and selecting those with low risk, even though they may exceed currently established tumor size criteria. 3. Evaluation of the effectiveness of liver transplantation for HCC requires an intent-to-treat approach that must include an accounting of the dropout rate of patients while waiting. 4. Locoregional pretransplantation adjuvant treatments may have some role for downstaging and/or reducing the dropout rate before transplantation, but their posttransplantation effect on outcome remains undetermined. 5. Liver allocation for HCC candidates in the context of increasing HCC prevalence requires better and evidence-based prioritization policies.

Carcinoma, Hepatocellular↗
PubMed2005

The survival benefit of liver transplantation.

Demand for liver transplantation continues to exceed donor organ supply. Comparing recipient survival to that of comparable candidates without a transplant can improve understanding of transplant survival benefit. Waiting list and post-transplant mortality was studied among a cohort of 12 996 adult patients placed on the waiting list between 2001 and 2003. Time-dependent Cox regression models were fitted to determine relative mortality rates for candidates and recipients. Overall, deceased donor transplant recipients had a 79% lower mortality risk than candidates (HR = 0.21; p < 0.001). At Model for End-stage Liver Disease (MELD) 18-20, mortality risk was 38% lower (p < 0.01) among recipients compared to candidates. Survival benefit increased with increasing MELD score; at the maximum score of 40, recipient mortality risk was 96% lower than that for candidates (p < 0.001). In contrast, at lower MELD scores, recipient mortality risk during the first post-transplant year was much higher than for candidates (HR = 3.64 at MELD 6-11, HR = 2.35 at MELD 12-14; both p < 0.001). Liver transplant survival benefit at 1 year is concentrated among patients at higher risk of pre-transplant death. Futile transplants among severely ill patients are not identified under current practice. With 1 year post-transplant follow-up, patients at lower risk of pre-transplant death do not have a demonstrable survival benefit from liver transplant.

Adolescent↗
PubMed2005

Regional variations in peer reviewed liver allocation under the MELD system.

The Model for End-Stage Liver Disease (MELD) is used to assign priority for liver transplantation candidates. The Organ Procurement and Transplantation Network (OPTN) approved recognized exceptional diagnoses (RED's) for which MELD fails to accurately measure priority. Centers can request increased MELD points in cases not recognized by this policy (non-RED's). Our aim was to compare regional practices to justify non-RED requests for MELD adjustments. The UNOS/OPTN database was queried to extract all adult cases for which a non-RED MELD adjustment was requested from 2/27/02 until 8/27/03. The data were stratified by region and justification. Data for 29,510 listings were available. 26,947 had complete diagnosis information. There were 827 non-RED requests of which 477 (57.7%) petitions were approved by the regional review boards (RRBs). The approval rate varied significantly among regions (range: 28-75%, p<0.0001). The most common non-RED's were complications of portal hypertension (48%). The percentage of patients listed with non-RED's varied significantly among regions (0.7-8.3 %, p<0.0001), as did the proportion of patients transplanted with non-RED's (2.1-31.9%, p<0.0001). Demographics did not differ among regions requesting non-REDs.Widespread regional variations exist in the handling of requests for non-REDs. These variations point to the need for reform to standard exception criteria.

Adult↗
PubMed2004

Risk factors for cytomegalovirus viremia and disease developing after prophylaxis in high-risk solid-organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) D+/R- solid-organ transplant (SOT) recipients carry increased risk of developing CMV disease; however, other risk factors in these patients have not been delineated. METHODS: We examined 20 demographic and clinical variables for their association with the development of CMV disease, as defined by an independent endpoint committee (IEC) and also by the investigator (investigator treated [IT]), or CMV viremia within 12 months of transplant in D+/R- transplant recipients who received prophylaxis with valganciclovir or oral ganciclovir for 100 days. RESULTS: Recipients with low creatinine clearance (Ccr,<40 mL/min) at screening had a significantly increased hazard of developing IEC-defined CMV disease (hazards ratio [HR]=4.28, confidence interval [CI] 1.69, 10.83). Females were twice as likely (HR=2.19, CI .21, 3.99) to develop IEC-defined CMV disease than males. These variables were associated with an increased risk of IEC-defined CMV disease in time-dependent models. Recipients with blood group A were also more likely to develop IEC-defined CMV disease than those with group O (HR=2.36 CI 1.24, 4.51) in the logistic regression model only. Prophylactic drug, organ type, recipient age, rejection episodes, and maintenance immunosuppression regimen were not associated with IEC-defined CMV disease. Female sex was the only variable associated with the development of CMV viremia (odds ratio [OR]=1.65; CI 1.03, 2.65) and IT CMV disease (OR=1.78; CI 1.08, 2.93). CONCLUSIONS: Low Ccr at screening and blood type A are risk factors for IEC-defined CMV disease, and female sex was a risk factor for IEC- and IT-defined CMV disease and viremia in high-risk SOT recipients. These variables should perhaps be considered when optimizing treatment.

ABO Blood-Group System↗
PubMed2004

Cytokine gene promoter polymorphisms and mortality in acute renal failure.

BACKGROUND: Although cytokines play a pivotal role in the inflammatory responses that mediate the severity of acute renal failure (ARF), the importance of pro- and anti-inflammatory cytokine gene promoter polymorphisms has been unexplored. METHODS: We prospectively evaluated the relationship of single nucleotide polymorphism in the promoter region of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) to mortality in 61 patients with ARF requiring intermittent hemodialysis. Cytokine genotyping was performed on leukocytes using PCR techniques. Cox proportional-hazards regression analysis was used to explore these relationships. RESULTS: The mean (+/-SD) APACHE II score was 24 +/- 7, MOF score 2 +/- 1, and 64% had sepsis. The TNF-alpha high producer genotype (-308 A-allele carrier) was associated with a higher risk of death after adjustment for the APACHE II score (HR=2.5; P=0.04), and the IL-10 intermediate/high producer genotype (-1082 G-allele carrier) was associated with a lower risk of death after adjustment for the MOF score (HR=0.36; P=0.03). Considering combinations of genotypes, the TNF-alpha high and IL-10 low producer genotype combination was associated with a approximately 6-fold increased risk of death compared to the TNF-alpha-low and IL-10 intermediate/high producer genotype combination, after adjustment for either APACHE II (P=0.004), MOF score (P=0.004) or sepsis (P=0.006). CONCLUSIONS: TNF-alpha and IL-10 gene polymorphisms are related to the risk of death among patients with ARF who require dialysis. Larger studies are needed to confirm these relationships.

Acute Kidney Injury↗
PubMed2004

MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status 1 patients.

The Model for End-Stage Liver Disease (MELD) score is predictive of survival and is used to prioritize patients with chronic liver disease patients for orthotopic liver transplantation (OLT). The aims of this study are (1) to assess the ability of MELD score at listing to predict pretransplant and posttransplant survival for nonchronic liver disease patients listed with the Organ Procurement and Transplantation Network/ United Network for Organ Sharing (OPTN/UNOS) as Status 1; and (2) to compare survival associated with 4 diagnostic groups within the Status 1 designation. The study population consisted of adult patients listed for OLT at Status 1 in the UNOS national database between November 1, 1999 and March 14, 2002 (N = 720). Events within 30 days of listing were analyzed using Kaplan-Meier and Cox regression methodology. Patients meeting criteria for fulminant hepatic failure without acetaminophen toxicity (FHF-NA, n = 312) had the poorest survival probability while awaiting OLT; this was negatively correlated with MELD score (P =.0001). These patients experienced the greatest survival benefit associated with OLT, with an estimated improvement of survival from about 58% to 91% (P <.0001). Patients listed for primary nonfunction within 7 days of OLT (n = 268) did not show mortality to be related to MELD score (P =.41) and did not show a significant association between survival and OLT (P =.68). In conclusion, liver allocation within the Status 1 designation may need to be further stratified by diagnosis, and MELD score may be useful for prioritizing FHF-NA candidates.

Adult↗
PubMed2004

Results of the first year of the new liver allocation plan.

Liver allocation policy in the U.S. was recently changed to a continuous disease severity scale with minimal weight given to time waiting in an effort to better prioritize deceased donor liver transplant candidates. We compared rates of waiting list registrations, removals, transplants, and deaths during the year prior to implementation of the new liver allocation policy (2/27/01-2/26/02, Era 1) with the first year's experience (2/27/02-2/26/03, Era 2) under this new policy. Rates were adjusted for 1,000 patient years on the waiting list and compared using z-tests. A 1-sided test was used to compare death rates; 2-sided tests were used to compare transplant rates. Overall and subgroup analyses were performed for demographic, geographic, and medical strata. In Era 2, we observed a 12% reduction in new liver transplant waiting list registrations, with the largest reductions seen in new registrants with low MELD/PELD scores. In Era 2, there was a 3.5% reduction in waiting list death rate (P =.076) and a 10.2% increase in cadaveric transplants (P <.001). The reduction in waiting list mortality and increase in transplantation rates were evenly distributed across all demographic and medical strata, with some variation across geographic variables. Early patient and graft survival after deceased donor liver transplantation remains unchanged. In conclusion, by eliminating the categorical waiting list prioritization system that emphasized time waiting, the new system has been associated with reduced registrations and improved transplantation rates without increased mortality rates for individual groups of waiting candidates or changes in early transplant survival rates.

Graft Survival↗
PubMed2004

Aerobic capacity is associated with 100-day outcome after hepatic transplantation.

The shortage of donor organs highlights the need to better identify patients most likely to benefit from hepatic transplantation. Reduced aerobic capacity (decreased peak oxygen consumption [VO(2)] during symptom-limited cardiopulmonary exercise testing) is frequently present in cirrhosis. Peak VO(2) during cardiopulmonary exercise testing may predict short-term outcome after hepatic transplantation. Symptom-limited testing was performed on a cycle ergometer (continuous ramp protocol) and VO(2) determined using a metabolic cart. One hundred fifty-six patients were tested; 59 subsequently underwent hepatic transplantation. Results showed that survivors and nonsurvivors were similar in age, duration of liver disease, Child-Pugh score, MELD score, resting cardiovascular function, pulmonary function, and gas exchange. The 6 (10.2%) patients dying within 100 days of transplantation were more likely to have reduced aerobic capacity (peak VO(2) <60% predicted and VO(2) at anaerobic threshold [VO(2)-AT] <50% predicted peak VO(2)) compared to survivors (4/6 vs. 7/53, P <.01). Using a multiple logistic regression model controlling for duration and severity of liver disease and time to transplantation, reduced aerobic capacity was independently associated with 100-day mortality. In conclusion, reduced aerobic capacity during cardiopulmonary exercise testing is associated with decreased short-term survival after hepatic transplantation. Further study is needed to determine if cardiopulmonary exercise testing can be used to improve allocation of donor organs. To ensure optimum allocation of donor organs, it is important to identify patients most likely to benefit from transplantation. Investigators have identified a number of preoperative, intraoperative, and postoperative factors that predict increased risk for postoperative mortality. Unfortunately, predictive accuracy has not been high, and the timing of factor identification does not optimize organ utilization. Identification of predictors of survival at the time of listing for transplantation might lead to better resource allocation.

Adult↗