Outcomes of liver transplantation for hepatocellular carcinoma (HCC) are determined by cancer-related and non-related events. Treatments for hepatitis C virus infection have reduced non-cancer events ...among patients receiving liver transplants, so reducing HCC-related death might be an actionable end point. We performed a competing-risk analysis to evaluate factors associated with survival of patients with HCC and developed a prognostic model based on features of HCC patients before liver transplantation.
We performed multivariable competing-risk regression analysis to identify factors associated with HCC-specific death of patients who underwent liver transplantation. The training set comprised 1018 patients who underwent liver transplantation for HCC from January 2000 through December 2013 at 3 tertiary centers in Italy. The validation set comprised 341 consecutive patients who underwent liver transplantation for HCC during the same period at the Liver Cancer Institute in Shanghai, China. We collected pretransplantation data on etiology of liver disease, number and size of tumors, patient level of α-fetoprotein (AFP), model for end-stage liver disease score, tumor stage, numbers and types of treatment, response to treatments, tumor grade, microvascular invasion, dates, and causes of death. Death was defined as HCC-specific when related to HCC recurrence after transplantation, disseminated extra- and/or intrahepatic tumor relapse and worsened liver function in presence of tumor spread. The cumulative incidence of death was segregated for hepatitis C virus status.
In the competing-risk regression, the sum of tumor number and size and of log10 level of AFP were significantly associated with HCC-specific death (P < .001), returning an average c-statistic of 0.780 (95% confidence interval, 0.763−0.798). Five-year cumulative incidence of non−HCC-related death was 8.6% in HCV-negative patients and 18.1% in HCV-positive patients. For patients with HCC to have a 70% chance of HCC-specific survival 5 years after transplantation, their level of AFP should be <200 ng/mL and the sum of number and size of tumors (in centimeters) should not exceed 7; if the level of AFP was 200−400 ng/mL, the sum of the number and size of tumors should be ≤5; if their level of AFP was 400−1000 ng/mL, the sum of the number and size of tumors should be ≤4. In the validation set, the model identified patients who survived 5 years after liver transplantation with 0.721 accuracy (95% confidence interval, 0.648%−0.793%). Our model, based on patients’ level of AFP and HCC number and size, outperformed the Milan; University of California, San Francisco; Shanghai-Fudan; Up-to-7 criteria (P < .001); and AFP French model (P = .044) to predict which patients will survive for 5 years after liver transplantation.
We developed a model based on level of AFP, tumor size, and tumor number, to determine risk of death from HCC-related factors after liver transplantation. This model might be used to select end points and refine selection criteria for liver transplantation for patients with HCC. To predict 5-year survival and risk of HCC-related death using an online calculator, please see www.hcc-olt-metroticket.org/. ClinicalTrials.gov ID NCT02898415.
Background & Aims Both hepatic resection and radiofrequency ablation (RFA) are considered curative treatments for hepatocellular carcinoma (HCC), but their economic impact still remains not ...determined. Aim of the present study was to analyze the cost-effectiveness (CE) of these two strategies in early stage HCC (Milan criteria). Methods As first step, a meta-analysis of the pertinent literature of the last decade was performed. Seventeen studies fulfilled the inclusion criteria: 3996 patients underwent resection and 4424 underwent RFA for early HCC. Data obtained from the meta-analysis were used to construct a Markov model. Costs were assessed from the health care provider perspective. A Monte Carlo probabilistic sensitivity analysis was used to estimate outcomes with distribution samples of 1000 patients for each treatment arm. Results In a 10-year perspective, for very early HCC (single nodule <2 cm) in Child–Pugh class A patients, RFA provided similar life-expectancy and quality-adjusted life-expectancy at a lower cost than resection and was the most cost-effective therapeutic strategy. For single HCCs of 3–5 cm, resection provided better life-expectancy and was more cost-effective than RFA, at a willingness-to-pay above € 4200 per quality-adjusted life-year. In the presence of two or three nodules ⩽3 cm, life-expectancy and quality-adjusted life-expectancy were very similar between the two treatments, but cost-effectiveness was again in favour of RFA. Conclusions For very early HCC and in the presence of two or three nodules ⩽3 cm, RFA is more cost-effective than resection; for single larger early stage HCCs, surgical resection remains the best strategy to adopt as a result of better survival rates at an acceptable increase in cost.
OBJECTIVES:To critically assess centralization policies for highly specialized surgeries in Europe and North America and propose recommendations.
BACKGROUND/METHODS:Most countries are increasingly ...forced to maintain quality medicine at a reasonable cost. An all-inclusive perspective, including health care providers, payers, society as a whole and patients, has ubiquitously failed, arguably for different reasons in environments. This special article follows 3 aimsfirst, analyze health care policies for centralization in different countries, second, analyze how centralization strategies affect patient outcome and other aspects such as medical education and cost, and third, propose recommendations for centralization, which could apply across continents.
RESULTS:Conflicting interests have led many countries to compromise for a health care system based on factors beyond best patient-oriented care. Centralization has been a common strategy, but modalities vary greatly among countries with no consensus on the minimal requirement for the number of procedures per center or per surgeon. Most national policies are either partially or not implemented. Data overwhelmingly indicate that concentration of complex care or procedures in specialized centers have positive impacts on quality of care and cost. Countries requiring lower threshold numbers for centralization, however, may cause inappropriate expansion of indications, as hospitals struggle to fulfill the criteria. Centralization requires adjustments in training and credentialing of general and specialized surgeons, and patient education.
CONCLUSION/RECOMMENDATIONS:There is an obvious need in most areas for effective centralization. Unrestrained, purely “market driven” approaches are deleterious to patients and society. Centralization should not be based solely on minimal number of procedures, but rather on the multidisciplinary treatment of complex diseases including well-trained specialists available around the clock. Audited prospective database with monitoring of quality of care and cost are mandatory.
We consider the general Landau-Lifshitz-Gilbert theory underlying the magnetization dynamics of a macrospin magnet subject to spin-torque effects and thermal fluctuations. Thermally activated ...dynamical properties are analyzed by averaging the full magnetization equations over constant-energy orbits. After averaging, all the relevant dynamical scenarios are a function of the ratio between hard and easy axis anisotropies. We derive analytically the range of currents for which limit cycles exist and discuss the regimes in which the constant energy orbit averaging technique is applicable.
This study was designed to demonstrate the need of accounting for respiration (R) when causality between heart period (HP) and systolic arterial pressure (SAP) is under scrutiny. Simulations ...generated according to a bivariate autoregressive closed-loop model were utilized to assess how causality changes as a function of the model parameters. An exogenous (X) signal was added to the bivariate autoregressive closed-loop model to evaluate the bias on causality induced when the X source was disregarded. Causality was assessed in the time domain according to a predictability improvement approach (i.e., Granger causality). HP and SAP variability series were recorded with R in 19 healthy subjects during spontaneous and controlled breathing at 10, 15, and 20 breaths/min. Simulations proved the importance of accounting for X signals. During spontaneous breathing, assessing causality without taking into consideration R leads to a significantly larger percentage of closed-loop interactions and a smaller fraction of unidirectional causality from HP to SAP. This finding was confirmed during paced breathing and it was independent of the breathing rate. These results suggest that the role of baroreflex cannot be correctly assessed without accounting for R.
We study the magnetization dynamics of spin-torque oscillators in the presence of thermal noise and as a function of the spin-polarization angle in a macrospin model. The macrospin has biaxial ...magnetic anisotropy, typical of thin film magnetic elements, with an easy axis in the film plane and a hard axis out of the plane. Using a method that averages the energy over precessional orbits, we derive analytic expressions for the current that generates and sustains out-of-plane precessional states. We find that there is a critical angle of the spin polarization necessary for the occurrence of such states and predict a hysteretic response to applied current. This model can be tested in experiments on orthogonal spin-transfer devices, which consist of both an in-plane and out-of-plane magnetized spin polarizers, effectively leading to an angle between the easy and spin-polarization axes.
Background
It remains unclear whether hepatectomy for hepatocellular carcinoma should be performed as an anatomic resection (AR) or a nonanatomic resection (NAR). Because no randomized controlled ...trials are currently available on this topic, a meta-regression analysis was performed on available observational studies to control for confounding variables.
Methods
A systematic review of studies published from 1990 to 2011 in the PubMed and Embase databases was performed. Patient and disease-free survival (DFS), postoperative mortality, and morbidity were considered as outcomes. Results are expressed as relative risk (RR) or weighted mean differences with 95 % of confidence interval.
Results
Eighteen observational studies involving 9,036 patients were analyzed: 4,012 were in the AR group and 5,024 in the NAR group. Meta-analysis suggested that AR provided better 5-year patient survival (RR 1.14;
P
= 0.001) and DFS than NAR (RR 1.38;
P
= 0.001). However, patients in the NAR group were characterized by a higher prevalence of cirrhosis (RR 1.27;
P
= 0.010), more advanced hepatic dysfunction (RR 0.90 for Child-Pugh class A;
P
= 0.001) and smaller tumor size (weighted mean difference 0.36 cm;
P
< 0.001) compared with patients in the AR group. Meta-regression analysis showed that the different proportion of cirrhosis in the NAR group significantly affected both 5-year patient survival (RR 1.28;
P
= 0.016) and DFS (RR 1.74;
P
= 0.022). Tumor size only slightly affected DFS (RR 1.72;
P
= 0.076). Postoperative mortality and morbidity were unaffected (
P
> 0.05 in all cases).
Conclusions
Patient survival and DFS after AR seem to be superior to NAR because the worse liver function reserve in the NAR group significantly affects prognosis.
Conventional criteria for liver transplantation for patients with hepatocellular carcinoma are single HCC ≤ 5 cm or less than or equal to three HCCs ≤ 3 cm. We prospectively evaluated the possibility ...of slightly extending these criteria in a down‐staging protocol, which included patients initially outside conventional criteria: single HCC 5–6 cm or two HCCs ≤ 5 cm or less than six HCCs ≤ 4 cm and sum diameter ≤ 12 cm, but within Milan criteria in the active tumors after the down‐staging procedures. The outcome of patients down‐staged was compared to that of Milan criteria after liver transplantation and since the first evaluation according to an intention‐to‐treat principle. From 2003 to 2006, 177 patients with HCC were considered for transplantation: the transplantation rate was comparable between the Milan and down‐staging groups: 88/129 cases (68%) versus 32/48 cases (67%), respectively. At a median follow‐up of 2.5 years after transplantation, the 1 and 3 years' disease‐free survival rates were comparable: 80% and 71% in the Milan group versus 78% and 71% in the down‐staging. The actuarial intention‐to‐treat survival was 27/48 patients (56.3%) in the down‐staging and 81/129 cases (62.8%) in the Milan group, p = n.s. The proposed down‐staging criteria provide a comparable outcome to the conventional criteria.
This study of a new down‐staging protocol for patients with HCC moderately beyond the Milan criteria on waiting list for liver transplantation shows that both the intention‐to‐treat analysis and the post‐operative outcome were comparable between down‐staging and conventional criteria group. See also editorial by Lo in this issue on page 2485.
PDF
