Electroporation is a well-known phenomenon that occurs at the cell membrane when cells are exposed to high-intensity electric pulses. Depending on electric pulse amplitude and number of pulses, ...applied electroporation can be reversible with membrane permeability recovery or irreversible. Reversible electroporation is used to introduce drugs or genetic material into the cell without affecting cell viability. Electrochemotherapy refers to a combined treatment: electroporation and drug injection to enhance its cytotoxic effect up to 1000-fold for bleomycin. Since several years, electrochemotherapy is gaining popularity as minimally invasive oncologic treatment. The adoption of electrochemotherapy procedure in interventional oncology poses several unsolved questions, since suitable tumor histology and size as well as therapeutic efficacy still needs to be deepen. Electrochemotherapy is usually applied in palliative settings for the treatment of patients with unresectable tumors to relieve pain and ameliorate quality of life. In most cases, it is used in the treatment of advanced stages of neoplasia when radical surgical treatment is not possible (eg, due to lesion location, size, and/or number). Further, electrochemotherapy allows treating tumor nodules in the proximity of important structures like vessels and nerves as the treatment does not involve tissue heating. Overall, the safety profile of electrochemotherapy is favorable. Most of the observed adverse events are local and transient, moderate local pain, erythema, edema, and muscle contractions during electroporation. The aim of this article is to review the recent published clinical experiences of electrochemotherapy use in deep-seated tumors with particular focus on liver cases. The principle of electrochemotherapy as well as the application to cutaneous metastases is briefly described. A short insight in the treatment of bone metastases, unresectable pancreas cancer, and soft tissue sarcoma will be given. Preclinical and clinical studies on treatment efficacy with electrochemotherapy of hepatic lesions and safety of the procedure adopted are discussed.
Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a paramagnetic hepatobiliary magnetic resonance (MR) contrast agent. Due to its OATP1B1/B3-dependent hepatocyte-specific ...uptake and paramagnetic properties increasing evidence has emerged to suggest that Gd-EOB-DTPA-enhanced MRI can be potentially used for evaluation of liver function. In this paper we compare the diagnostic performance of Gd-EOB-DTPA-enhanced relaxometry-based and commonly used signal-intensity (SI)-based indices, including the hepatocellular uptake index (HUI) and SI-based indices corrected by spleen or muscle, for evaluation of liver function, determined using the Indocyanin green clearance (ICG) test. Simple linear regression model showed a significant correlation of the plasma disappearance rate of ICG (ICG-PDR) with all Gd-EOB-DTPA-enhanced MRI-based liver function indices with a significantly better correlation of relaxometry-based indices on ICG-PDR compared to SI-based indices. Among SI-based indices, HUI achieved best correlation on ICG-PDR and no significant difference of respective correlations on ICG-PDR could be shown. Assessment of liver volume and consecutive evaluation of multiple linear regression model revealed a stronger correlation of ICG-PDR with both (SI)-based and T1 relaxometry-based indices. Thus, liver function can be estimated quantitatively from Gd-EOB-DTPA-enhanced MRI-based indices. Here, indices derived from T1 relaxometry are superior to SI-based indices, and all indices benefit from taking into account respective liver volumes.
The application of navigational systems has the potential to improve percutaneous interventions. The accuracy of ablation probe placement can be increased and radiation doses reduced. Two different ...types of systems can be distinguished, tracking systems and robotic systems. This review gives an overview of navigation devices for clinical application and summarizes first findings in the implementation of navigation in percutaneous interventions using irreversible electroporation. Because of the high number of navigation systems, this review focuses on commercially available ones.
In this study, we compare the primary efficacy of computed tomography-navigated stereotactic guidance to that of manual guidance for percutaneous microwave ablation of liver malignancies. In total, ...221 patients (140, 17, and 64 with hepatocellular carcinoma, cholangiocellular carcinoma, and liver metastases, respectively) with 423 treated liver lesions underwent microwave ablation (MWA). Manual guidance (M) and stereotactic guidance (S) were used for 136 and 287 lesions, respectively. The primary endpoint was the primary efficacy and the secondary endpoint was the radiation dose. A generalised estimating equation was applied to analyse the correlation between the primary efficacy (lesion basis) and the type of guidance, size and location of lesion. The primary efficacy rate was significantly higher in the S-group (84.3%) than in the M-group (75.0%, p = 0.03). Lesion size > 30 mm was negatively correlated with the efficacy rate (odds ratio 0.38; 95% confidence interval 0.20-0.74). Stereotactic guidance was associated with a significantly lower dose length product (p < 0.01). In this retrospective study, percutaneous microwave ablation under stereotactic guidance exhibited significantly greater primary efficacy than conventional manual guidance.
To assess the differences between normal and cirrhotic livers by means of T1 mapping of liver parenchyma on gadoxetic acid (Gd-EOB-DTPA)-enhanced 3 Tesla (3T) MR imaging (MRI).
162 patients with ...normal (n = 96) and cirrhotic livers (n = 66; Child-Pugh class A, n = 30; B, n = 28; C, n = 8) underwent Gd-EOB-DTPA-enhanced 3T MRI. To obtain T1 maps, two TurboFLASH sequences (TI = 400 ms and 1000 ms) before and 20 min after Gd-EOB-DTPA administration were acquired. T1 relaxation times of the liver and the reduction rate between pre- and post-contrast enhancement images were measured.
The T1 relaxation times for Gd-EOB-DTPA-enhanced MRI showed significant differences between patients with normal liver function and patients with Child-Pugh class A, B, and C (p < 0.001). The T1 relaxation times showed a constant significant increase from Child-Pugh class A up to class C (Child-Pugh class A, 335 ms ± 80 ms; B, 431 ms ± 75 ms; C, 557 ms ± 99 ms; Child-Pugh A to B, p < 0.001; Child-Pugh A to C, p < 0.001; Child-Pugh B to C, p < 0.001) and a constant decrease of the reduction rate of T1 relaxation times (Child-Pugh class A, 57.1% ± 8.8%; B, 44.3% ± 10.2%, C, 29.9% ± 6.9%; Child-Pugh A to B, p < 0.001; Child-Pugh A to C,p < 0.001; Child-Pugh B to C, p < 0.001).
Gd-EOB-DTPA-enhanced T1 mapping of the liver parenchyma may present a useful method for determining severity of liver cirrhosis.
Monitoring disease progression is particularly important for determining the optimal treatment strategy in patients with liver disease. Especially for patients with diseases that have a reversible ...course, there is a lack of suitable tools for monitoring liver function. The development and establishment of such tools is very important, especially in view of the expected increase in such diseases in the future. Image-based liver function parameters, such as the T1 relaxometry-based MELIF score, are ideally suited for this purpose. The determination of this new liver function score is fully automated by software developed with AI technology. In this study, the MELIF score is compared with the widely used ALBI score. The ALBI score was used as a benchmark, as it has been shown to better capture the progression of less severe liver disease than the MELD and Child‒Pugh scores. In this study, we retrospectively determined the ALBI and MELIF scores for 150 patients, compared these scores with the corresponding MELD and Child‒Pugh scores (Pearson correlation), and examined the ability of these scores to discriminate between good and impaired liver function (AUC: MELIF 0.8; ALBI 0.77) and to distinguish between patients with and without cirrhosis (AUC: MELIF 0.83, ALBI 0.79). The MELIF score performed more favourably than the ALBI score and may also be suitable for monitoring mild disease progression. Thus, the MELIF score is promising for closing the gap in the available early-stage liver disease monitoring tools (i.e., identification of liver disease at a potentially reversible stage before chronic liver disease develops).
5-Fluorouracil (5FU), Folinic acid (FA), and Oxaliplatin (FOLFOX) or 5FU, FA, and Irinotecan (FOLFIRI) are standard regimens for palliative chemotherapy of metastatic colon cancer. Since data showing ...the influence of dose reduction in palliative treatment are rare, the objective of this single center, retrospective study was to further characterize the influence of dose reduction on efficacy of these therapeutic regimens.
One hundred nine patients, diagnosed with stage IV colon cancer between 2004 and 2012 and receiving palliative first-line chemotherapy with either FOLFOX or FOLFIRI regimens in our outpatient clinic were analyzed for treatment efficacy. Patients who received dose reductions due to side effects usually received doses of 80% or lower of per protocol dose. Survival data were obtained from the Regensburg Tumor Registry. Survival analysis was performed using Kaplan-Meier statistical analysis and multivariable analysis.
A dose reduction due to side effects was necessary in 46 (42%) patients. Dose reduction was independent of age. Major reasons for dose reduction were neutropenia (30%) followed by polyneuropathy (16%) and diarrhea (14%). Dosage was more often reduced in patients receiving FOLFOX based therapy. Comparison of patients with dose reduction versus patients with full dosage showed no significant difference on overall survival (p = 0.430). Subgroup analysis revealed dose reduction in patients with N2 stage disease was associated with improved survival. Patients who underwent dose reduction received more cycles of chemotherapy (13.7 vs. 10.8 cycles) and cumulative dosage was similar in both groups.
Contrary to our expectations, the need to reduce chemotherapy dosage due to side effects does not indicate a worse prognosis in our retrospective analysis. We believe this can in part be explained by better adaption to interindividual pharmacokinetics and longer time of treatment.
Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a hepatocyte-specific MRI contrast agent. Because the hepatic uptake of Gd-EOB-DTPA depends on the integrity of the ...hepatocyte mass, this uptake can be quantified to assess liver function. We report the relationship between the extent of Gd-EOB-DTPA uptake and the degree of liver fibrosis. T1-weighted volume-interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 minutes after contrast injection. Strong correlations of the uptake characteristics of Gd-EOB-DTPA with the relative enhancement (RE) of the liver parenchyma and the grade of fibrosis/cirrhosis, classified using the Ishak scoring system, were observed. The subdivisions between the grades of liver fibrosis based on RE were highly significant for all combinations, and a ROC revealed sensitivities ≥82% and specificities ≥87% for all combinations. MR imaging is a satisfactorily sensitive method for the assessment of liver fibrosis/cirrhosis.
Using new perfusion software for evaluation of the success of percutaneous treatments of malignant liver tumors with CEUS.
Retrospective analysis of 88 patients (74 male, 14 female; 30 - 84 years) ...with 165 malignant liver lesions. The lesions were 57 metastases and 108 HCCs. The success of interventional treatment (IRE n = 47; RFA n = 38; MWA n = 44; TACE n = 36) was evaluated by CEUS and perfusion software (VueBox
). CEUS was performed after injection of 1 - 2.4 ml of sulfur hexafluoride microbubbles (SonoVue
) using a 1 - 5 MHz convex probe. DICOM loops up to 1 min. in the ablation area were stored digitally in the PACS. Regions of interest (ROI) were manually placed in the center, the margins of the lesions as well as in the surrounding tissue. Using VueBox
peak, time to peak (TTP), mean transit time (mTT), rise time (RT), the wash-in and wash-out rate were calculated for the regions, in order to evaluate the success of the percutaneous treatment after the ablation in comparison to the ceCT/ceMRI up to 6 months after the treatment.
There were significant differences in all cases between the center compared to the margins for the main perfusion parameters (peak, mTT, RT) (p < 0.001). Peak, wash-in and wash-out ratios were further analyzed with the type of lesion and the method of ablation. All parameters were significantly different between lesions treated successfully vs. lesions with recurrence.
A combination of CEUS with perfusion imaging enables critical assessment of successful treatment after percutaneous interventional procedures for a malignant liver lesion.
Gd-EOB-DTPA, a liver-specific contrast agent with T1-shortening effects, is routinely used in clinical routine for detection and characterization of focal liver lesions and has recently received ...increasing attention as a tool for the quantitative analyses of liver function. We report the relationship between the extent of Gd-EOB-DTPA- induced T1 relaxation and the degree of liver fibrosis, which was assessed according to the METAVIR score. For the T1 relaxometry, a transverse 3D VIBE sequence with inline T1 calculation was acquired prior to and 20 minutes after Gd-EOB-DTPA administration. The reduction rates of the T1 relaxation time (rrT1) between the pre- and postcontrast images were calculated, and the optimal cutoff values for the fibrosis stages were determined with receiver operating characteristic (ROC) curve analyses. The rrT1 decreased with the severity of liver fibrosis and regression analysis revealed a significant correlation of the rrT1 with the stage of liver fibrosis (r = -0.906, p < 0.001). ROC analysis revealed sensitivities ≥78% and specificities ≥94% for the differentiation of different fibrosis stages. Gd-EOB-DTPA-enhanced T1 relaxometry is a reliable tool for both the detection of initial hepatic fibrosis and the staging of hepatic fibrosis.
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