Alpha-Fetoprotein (AFP) and AFP-L3 Is Most Useful in Detection of Recurrence of Hepatocellular Carcinoma in Patients after Tumor Ablation and with Low AFP Level.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is a leading cause of mortality worldwide. While there are many risk factors for HCC including alcohol, obesity, and diabetes, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection still account for the majority of HCC worldwide. Globally, HBV is the leading risk factor for HCC. Patients with chronic hepatitis B (CHB) and advanced liver disease are at high risk for HCC. Screening for HCC is done routinely with ultrasound with or without alpha-fetoprotein (AFP) at six-month intervals. The combination of ultrasound and AFP has been shown to provide some additional detection of 6-8% of cases compared to ultrasound alone; however, this also increases false-positive results. This is because AFP can be elevated not only in the setting of HCC, but also in chronic hepatitis, liver cirrhosis, or ALT flare in CHB, which limits the specificity of AFP. AFP-L3 is a subfraction of AFP that is produced by malignant hepatocytes. The ratio of AFP-L3 to total AFP is reported as a percentage, and over 10% AFP-L3 is consistent with a diagnosis of HCC. Here, we review five cases of patients with CHB, cirrhosis, and HCC, and their levels of AFP and the AFP-L3% at various stages of disease including ALT flare, cirrhosis, initial diagnosis of HCC, and recurrence of HCC. These cases emphasize the utility of AFP-L3% in identifying early, new or recurrent HCC prior to the presence of imaging findings.

Hemodynamic Evaluation of Avalon Elite Bi-Caval Dual Lumen Cannulas and Femoral Arterial Cannulas.

Translational research is a useful tool to provide scientific evidence for cannula selection during extracorporeal life support (ECLS). The objective of this study was to evaluate four Avalon Elite bi-caval dual lumen cannulas and nine femoral arterial cannulas in terms of flow range, circuit pressure, pressure drop, and hemodynamic energy transmission in a simulated adult ECLS model. A veno-venous ECLS circuit was used to evaluate four Avalon Elite bi-caval dual lumen cannulas (20, 23, 27, and 31 Fr), and a veno-arterial ECLS circuit was used to evaluate nine femoral arterial cannulas (15, 17, 19, 21, and 23 Fr). The two circuits included a Rotaflow centrifugal pump, a Quadrox-D adult oxygenator, and 3/8 in ID tubing for arterial and venous lines. The circuits were primed with lactated Ringer's solution and packed human red blood cells (hematocrit 40%). Trials were conducted at rotational speeds from 1000 to 5000 RPM (250 rpm increments) for each Avalon cannula, and at different flow rates (0.5-7 L/min) for each femoral arterial cannula. Real-time pressure and flow data were recorded for analysis. Small caliber cannulas created higher circuit pressures, higher pressure drops and higher M-numbers compared with large ones. The inflow side of Avalon dual lumen cannula had a significantly higher pressure drop than the outflow side (inflow vs. outflow: 20 Fr-100.2 vs. 49.2 mm Hg at 1.1 L/min, 23 Fr-93.7 vs. 41.4 mm Hg at 1.6 L/min, 27 Fr-102.3 vs. 42.8 mm Hg at 2.6 L/min, 31 Fr-98.1 vs. 44.7 mm Hg at 3.8 L/min). There was more hemodynamic energy lost in the veno-arterial ECLS circuit using small cannulas compared to larger ones (17 Fr vs. 19 Fr vs. 21 Fr at 4 L/min-Medtronic: 71.0 vs. 64.8 vs. 60.9%; Maquet: 71.4 vs. 65.6 vs. 62.0%). Medtronic femoral arterial cannulas had lower pressure drops (Medtronic vs. Maquet at 4 L/min: 17 Fr-121.7 vs. 125.0 mm Hg, 19 Fr-71.2 vs. 73.7 mm Hg, 21 Fr-42.9 vs. 47.4 mm Hg) and hemodynamic energy losses (Medtronic vs. Maquet at 4 L/min: 17 Fr-43.6 vs. 44.4%, 19 Fr-31.0 vs. 31.4%, 21 Fr-20.8 vs. 22.4%) at high flow rates when compared with the Maquet cannulae. The results for this study provided valuable hemodynamic characteristics of all evaluated adult cannulas with human blood in order to guide ECLS cannula selection in clinical practice. Use of larger cannulas are suggested for VV- and VA-ECLS.

Impact of Heart Rate on Pulsatile Hemodynamic Performance in a Neonatal ECG-Synchronized ECLS System.

The experimental circuit consisted of an i-cor diagonal pump, a Medos Hilite 800 LT oxygenator, an 8Fr Biomedicus arterial cannula, a 10Fr Biomedicus venous cannula, and six feet of 1/4 in ID tubing for arterial and venous lines. The circuit was primed with lactated Ringer's solution and packed red blood cells (hematocrit 40%). Trials were conducted at various heart rates (90, 120, and 150 bpm) and flow rates (200, 400, and 600mL/min) under nonpulsatile and pulsatile mode with pulsatile amplitudes of 1000-4000rpm (1000 rpm increments). Real-time pressure and flow data were recorded for analysis. The i-cor pump was capable of creating nonpulsatile and electrocardiography (ECG)-synchronized pulsatile flow, and automatically reducing pulsatile frequency by increasing the assist ratio at higher heart rates. Reduced pulsatile frequency led to lower hemodynamic energy generation but did not affect circuit pressure drop. Pulsatile flow delivered more hemodynamic energy to the pseudopatient when compared with nonpulsatile flow. The pump generated more hemodynamic energy with higher pulsatile amplitudes. The i-cor pump can automatically adjust the pulsatile assist ratio to create pulsatile flow at higher heart rates, although this caused some hemodynamic energy loss. Compared with nonpulsatile flow, pulsatile flow generated and transferred more hemodynamic energy to the neonate during ECLS (200-600mL/min), especially at high pulsatile amplitudes and low flow rates.

Evaluation of Two Femoral Arterial Cannulae With Conventional Non-Pulsatile and Alternative Pulsatile Flow in a Simulated Adult ECLS Circuit.

The objective of this study is to evaluate the hemodynamic characteristics of two femoral arterial cannulae in terms of circuit pressure, pressure drop, and hemodynamic energy transmission under non-pulsatile and pulsatile modes in a simulated adult extracorporeal life support (ECLS) system. The ECLS circuit consisted of i-cor diagonal pump and console (Xenios AG, Heilbronn, Germany), an iLA membrane ventilator (Xenios AG), an 18 Fr or 16 Fr femoral arterial cannula (Xenios AG), and a 23/25 Fr Estech remote access perfusion (RAP) femoral venous cannula (San Ramon, CA, USA). The circuit was primed with lactated Ringer's solution and packed red blood cells to achieve a hematocrit of 35%. All trials were conducted at room temperature with flow rates of 1-4 L/min (1 L/min increments). The pulsatile flow settings were set at pulsatile frequency of 75 bpm and pulsatile amplitudes of 1000-4000 rpm (1000 rpm increments). Flow and pressure data were collected using a custom data acquisition system. Total hemodynamic energy (THE) is calculated by multiplying the ratio between the area under the hemodynamic power curve (∫flow × pressure dt) and the area under the pump flow curve (∫flow dt) by 1332. The pressure drop across the arterial cannula increased with increasing flow rate and decreasing cannula size. The pressure drops of 18 Fr and 16 Fr cannulae were 19.4-24.5 and 38.4-45.3 mm Hg at 1 L/min, 55.2-56.8 and 110.9-118.3 mm Hg at 2 L/min, 94.1-105.1 and 209.7-215.1 mm Hg at 3 L/min, and 169.2-172.6 and 376.4 mm Hg at 4 L/min, respectively. Pulsatile flow created more hemodynamic energy than non-pulsatile flow, especially at lower flow rates. The percentages of THE loss across 18 Fr and 16 Fr cannula were 16.0-18.7 and 27.5-30.8% at 1 L/min, 35.1-35.7 and 52.3-53.8% at 2 L/min, 48.3-50.3 and 67.3-68.4% at 3 L/min and 62.9-63.1 and 79.0% at 4 L/min. The hemodynamic performance of the arterial cannula should be evaluated before use in clinical practice. The pressure drops and percentages of THE loss across two cannulae tested using human blood were higher compared to the manufacturer's data tested using water. The cannula size should be chosen to match the expected flow rate. In addition, this novel i-cor ECLS system can provide non-pulsatile and ECG-synchronized pulsatile flow without significantly increasing the cannula pressure drop and hemodynamic energy loss.

Effects of Pulsatile Control Algorithms for Diagonal Pump on Hemodynamic Performance and Hemolysis.

The objective of this study is to compare hemodynamic performances under different pulsatile control algorithms between Medos DeltaStream DP3 and i-cor diagonal pumps in simulated pediatric and adult ECLS systems. An additional pilot study was designed to test hemolysis using two pumps during 12h-ECLS. The experimental circuit consisted of parallel combined pediatric and adult ECLS circuits using an i-cor pump head and either an i-cor console or Medos DeltaStream MDC console, a Medos Hilite 2400 LT oxygenator for the pediatric ECLS circuit, and a Medos Hilite 7000 LT oxygenator for the adult ECLS circuit. The circuit was primed with lactated Ringer's solution and human packed red blood cells (hematocrit 40%). Trials were conducted at various flow rates (pediatric circuit: 0.5 and 1L/min; adult circuit: 2 and 4L/min) under nonpulsatile and pulsatile modes (pulsatile amplitude: 1000-5000rpm [1000 rpm increments] for i-cor pump, 500-2500rpm [500 rpm increments] for Medos pump) at 36°C. In an additional protocol, fresh whole blood was used to test hemolysis under nonpulsatile and pulsatile modes using the two pump systems in adult ECLS circuits. Under pulsatile mode, energy equivalent pressures (EEP) were always greater than mean pressures for the two systems. Total hemodynamic energy (THE) and surplus hemodynamic energy (SHE) levels delivered to the patient increased with increasing pulsatile amplitude and decreased with increasing flow rate. The i-cor pump outperformed at low flow rates, but the Medos pump performed superiorly at high flow rates. There was no significant difference between two pumps in percentage of THE loss. The plasma free hemoglobin level was always higher in the Medos DP3 pulsatile group at 4 L/min compared to others. Pulsatile control algorithms of Medos and i-cor consoles had great effects on pulsatility. Although high pulsatile amplitudes delivered higher levels of hemodynamic energy to the patient, the high rotational speeds increased the risk of hemolysis. Use of proper pulsatile amplitude settings and intermittent pulsatile mode are suggested to achieve better pulsatility and decrease the risk of hemolysis. Further optimized pulsatile control algorithms are needed.

In Vitro Hemodynamic Evaluation of ECG-Synchronized Pulsatile Flow Using i-Cor Pump as Short-Term Cardiac Assist Device for Neonatal and Pediatric Population.

The objective of this study was to assess the hemodynamic properties of the i-cor ECG-synchronized cardiac assist system for off-label use as a short-term cardiac assist device for neonatal and pediatric patients and compare nonpulsatile to pulsatile flow with different amplitudes. The circuit consisted of the i-cor diagonal pump with 3 feet of » inch arterial and venous tubing and a soft-shell reservoir, primed with lactated Ringer's solution and human packed red blood cells (hematocrit 42%). Trials were conducted with three different sets of cannulas (8-Fr arterial 10-Fr venous, 10-Fr arterial 12 Fr-venous, and 12-Fr arterial 14-Fr venous) with increasing flow rates at varying pseudo-patient pressures (40, 60, 80, and 100 mm Hg) and under nonpulsatile mode and pulsatile mode with pulsatile amplitudes 2000, 2500, and 3000 rpm at 36°C. Pressure and flow waveforms were recorded using a custom-made data acquisition device for each trial. Energy equivalent pressure (EEP) was higher than mean pressure under pulsatile mode, and increased with increasing pseudo-patient's pressure and flow rate while EEP was the same as the mean pressure under nonpulsatile mode. Total hemodynamic energy (THE) levels increased with pressure and pulsatile amplitude and slightly decreased with increasing flow rate. The percent THE lost throughout the circuit increased with flow rate and pulsatile amplitude and decreased with pseudo-patient's pressure. SHE levels also increased with pseudo-patient pressure and pulsatile amplitude and decreased with increasing flow rate. The i-cor diagonal pump can be used as a short term cardiac assist device for neonatal and pediatric patients and is able to provide nonpulsatile as well as pulsatile flow. Compared with nonpulsatile flow, pulsatile flow can generate and deliver more hemodynamic energy to the patients.

In Vitro Evaluation of ECG-Synchronized Pulsatile Flow Using the i-cor Diagonal Pump in Neonatal and Pediatric ECLS Systems.

The objective was to assess the i-cor electrocardiogram-synchronized diagonal pump in terms of hemodynamic energy properties for off-label use in neonatal and pediatric extracorporeal life support (ECLS) circuits. The neonatal circuit consisted of an i-cor pump and console, a Medos Hilite 800 LT oxygenator, an 8Fr arterial cannula, a 10Fr venous cannula, 91 cm of 0.6-cm ID arterial tubing, and 91 cm of 0.6-cm ID venous tubing. The pediatric circuit was identical except it included a 12Fr arterial cannula, a 14Fr venous cannula, and a Medos Hilite 2400 LT oxygenator. Neonatal trials were conducted at 36°C with hematocrit 40% using varying flow rates (200-600 mL/min, 200 mL increments) and postarterial cannula pressures (40-100 mm Hg, 20 mm Hg increments) under nonpulsatile mode and pulsatile mode with various pulsatile amplitudes (1000-4000 rpm, 1000 rpm increments). Pediatric trials were conducted at different flow rates (800-1600 mL/min, 400 mL/min increments). Mean pressure and energy equivalent pressure increased with increasing postarterial cannula pressure, flow rate, and pulsatile amplitude. Physiologic-like pulsatility was achieved between pulsatile amplitudes of 2000-3000 rpm. Pressure drops were greatest across the arterial cannula. Pulsatile flow generated significantly higher total hemodynamic energy (THE) levels than nonpulsatile flow. THE levels at postarterial cannula site increased with increasing postarterial cannula pressure, pulsatile amplitude, and flow rate. No surplus hemodynamic energy (SHE) was generated under nonpulsatile mode. Under pulsatile mode, preoxygenator SHE increased with increasing postarterial cannula pressure and pulsatile amplitude, but decreased with increasing flow rate. The i-cor system can provide nonpulsatile and pulsatile flow for neonatal and pediatric ECLS. Pulsatile amplitudes of 2000-3000 rpm are recommended for use in neonatal and pediatric patients.

In Vitro Comparison of Pediatric Oxygenators With and Without Integrated Arterial Filters in Maintaining Optimal Hemodynamic Stability and Managing Gaseous Microemboli.

The purpose of this study was to compare the Capiox FX15 oxygenator with integrated arterial filter to the Capiox RX15 oxygenator with separate Capiox AF125 arterial filter in terms of hemodynamic properties and gaseous microemboli (GME) capturing. Trials were conducted at varying flow rates (2.0 L/min, 3.0 L/min, 4.0 L/min), temperatures (30°C, 35°C), and flow modalities (pulsatile, nonpulsatile). Pressure and flow waveforms were recorded using a custom-made data acquisition system. GME data were recorded using an Emboli Detection and Classification Quantifier after injecting a 5 mL air bolus into the venous line. Maximum instantaneous pre-oxygenator flows reached 7.4 L/min under pulsatile conditions when the roller pump was set to a flow rate of 4 L/min. Mean pressure drops were slightly greater in the FX15 group (P < 0.0001), and the diverted flow from the arterial purge line was slighter greater in the FX15 group at 3 L/min and 4 L/min (P < 0.0001). There was a slight generation of surplus hemodynamic energy (SHE) at the pre-oxygenator site for both oxygenators under "nonpulsatile mode." However, higher pre-oxygenator SHE levels were recorded for both groups with "pulsatile mode." The RX15 and FX15 groups were both able to remove all microemboli from the circuit at 2 L/min and 3 L/min in "nonpulsatile mode." Microemboli were delivered to the patient at 4 L/min with pulsatile flows in both groups. The RX15 oxygenator with separate AF125 arterial filter and FX15 oxygenator with integrated arterial filter performed similarly in terms of hemodynamic performance and microemboli capturing. Pulsatile flows at 4 L/min produced instantaneous flow rates that surpassed the documented maximum flow rates of the oxygenators and might have contributed to the delivery of GME to the pseudo-patient.

In Vitro Comparison of Two Neonatal ECMO Circuits Using a Roller or Centrifugal Pump With Three Different In-Line Hemoconcentrators for Maintaining Hemodynamic Energy Delivery to the Patient.

The objective of this study was to compare three different hemoconcentrators (Hemocor HPH 400, Mini, and Junior) with two different neonatal ECMO circuits using a roller or a centrifugal pump at different pseudo-patient pressures and flow rates in terms of hemodynamic properties. This evidence-based research is necessary to optimize the ECMO circuitry for neonates. The circuits used a 300-mL soft-shell reservoir as a pseudo-patient approximating the blood volume of a 3 kg neonate, two blood pumps, and a Quadrox-iD Pediatric oxygenator with three different in-line hemoconcentrators (Hemocor HPH 400, Mini, and Junior). One circuit used a Maquet H20 roller pump and another circuit used a Maquet RotaFlow centrifugal pump. The circuit was primed with lactated Ringer's solution followed by heparinized packed red blood cells with a hematocrit of 40%. The pseudo-patient's pressure was manually maintained at 40, 60, or 80 mm Hg and the flow rate was maintained at 200, 400, or 600 mL/min with a circuit temperature of 36°C. Pressure and flow data was recorded using a custom-made data acquisition device. Mean pressures, diverted blood flow, pressure drops, and total hemodynamic energy (THE) were calculated for each experimental condition. The roller pump and centrifugal pump performed similarly for all hemodynamic properties with all experimental conditions. The Hemocor HPH Junior hemoconcentrator added the highest resistance to the circuit. The Hemocor HPH Junior provided the highest circuit pressures, lowest diverted blood flow, highest pressure drop across the circuit, and highest THE generated by the pump. The Hemocor HPH 400 added the least resistance to the circuit, providing the lowest circuit pressures, more diverted flow, lowest pressure drop, and the lowest THE generated by the pump. However, the THE delivered to the patient was the same for the three hemoconcentrators. While the three hemoconcentrators performed differently in terms of hemodynamic properties throughout the circuit, the THE transmitted to the patient was similar for all three hemoconcentrators due to the consistent pseudo-patient's pressure that was manually maintained for each trial. While the THE delivered to the patient indicates similar perfusion for these patients with any of the three hemoconcentrators, the differences in added resistance to the circuit may impact the decision of which hemoconcentrator is used. There was no clinically significant difference between the two circuits with the roller versus centrifugal pump in terms of hemodynamic properties in this study. Further in vivo research is warranted to confirm our findings.