Safety margin assessment after microwave ablation of liver tumors: inter- and intrareader variability

Background. The aim of the study was to evaluate the inter- and intrareader variability of the safety margin assessment after microwave ablation of liver tumors using post-procedure computed tomography (CT) images as well as to determine the sensitivity and specificity of identification remnant tumor tissue. Patients and methods. A retrospective analysis of 58 patients who underwent microwave ablation (MWA) of primary or secondary liver malignancies (46 hepatocellular carcinoma, 9 metastases of a colorectal cancer and 3 metastases of pancreatic cancer) between September 2017 and June 2019 was conducted. Three readers estimated the minimal safety margin in millimeters using side-by-side comparison of the 1-day pre-ablation CT and 1-day postablation CT and judged whether ablation was complete or incomplete. One reader estimated the safety margin again after 6 weeks. Magnetic resonance imaging (MRI) after 6 weeks was the gold standard. Results. The intraclass correlation coefficient (ICC) for estimation of the minimal safety margin of all three readers was 0.357 (95%-confidence interval 0.194-0.522). The ICC for repeated assessment (reader 1) was 0.774 (95%-confidence interval 0.645-0.860). Sensitivity and specificity of the detection of complete tumor ablation, defined as no remnant tumor tissue in 6 weeks follow-up MRI, were 93%/82%/82% and 33%/17%/83%, respectively. Conclusions. In clinical practice, the safety margin after liver tumor ablation is often assessed using side-by-side comparison of CT images. In the study, we were able to show, that this technique has a poor reliability (ICC 0.357). From our point of view, this proves the necessity of new technical procedures for the assessment of the safety distance

Phage mediated horizontal transfer of the sopE1 gene increases enteropathogenicity of Salmonella enterica serotype Typhimurium for calves

Epidemiological evidence shows that the sopE1 gene is associated with Salmonella Typhimurium phage types causing epidemics in cattle. In this study we demonstrate that horizontal transfer of the sopE1 gene by lysogenic conversion with the SopEΦ increased enteropathogenicity of S. Typhimurium in the bovine ligated ileal loop model. These data support the hypothesis that phage mediated horizontal transfer of the sopE1 gene contributes to the emergence of epidemic cattle-associated S. Typhimurium clone

Early Detection of Local Tumor Progression after Irreversible Electroporation (IRE) of a Hepatocellular Carcinoma Using Gd-EOB-DTPA-Based MR Imaging at 3T

Simple Summary Liver tumors like hepatocellular carcinoma (HCC) can be treated minimally invasive, e.g., by Irreversible Electroporation (IRE), which destroys the cancer. As it is possible that the tumor re-grows due to single tumor cells inadvertently not covered by the treatment, follow-up imaging of the liver is important for early detection of local tumor progression. As ablation leaves scarred tissue, recurrent tumor after IRE can appear vastly different than before treatment and thus can be hard to detect on MRI via classical imaging features. We here examined cases of local tumor progression after IRE of HCC and found distinct MR-imaging features helpful for the identification of re-grown viable tumor, namely T2 BLADE and diffusion weighted images (DWI) at the ablation zone border and T1 portal-venous and delayed phase post-contrast images in the center of the ablation zone. This knowledge will help in early detection and re-treatment of HCC for a prolonged survival. Abstract This single-center retrospective study was conducted to improve the early detection of local tumor progression (LTP) after irreversible electroporation (IRE) of a hepatocellular carcinoma (HCC) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-based 3T MR imaging and to identify helpful signal characteristics by comparing 23 patients with and 60 patients without LTP. To identify the differences in the sensitivity of MRI sequences, the specificity, positive prediction value, negative prediction value (NPV) and diagnostic odds ratio were calculated. A chi-squared test, two-tailed student’s t-test and binary logistic regression model were used to detect distinct patient characteristics and variables for the prediction of LTP. LTP was mostly detected in the peripheral ablation zone (82.6%) within the first six months (87.0%). The central LTP ablation area presented more hypointensities in T1 p.v. (sensitivity: 95.0%; NPV: 90.0%) and in T1 d.p. (sensitivity: 100.0%; NPV: 100.0) while its peripheral part showed more hyperintensities in T2 BLADE (sensitivity: 95.5%; NPV: 80.0%) and in diffusion sequences (sensitivity: 90.0%). Liver cirrhosis seems to be an unfavorable prognosticator for LTP (p = 0.039). In conclusion, LTP mostly occurs in the peripheral ablation zone within six months after IRE. Despite often exhibiting atypical Gd-EOB-DTPA MR signal characteristics, T2 BLADE and diffusion sequences were helpful for their detection in the peripheral zone while T1 p.v. and T1 d.p. had the highest sensitivity in the central zone

Detection of Incomplete Irreversible Electroporation (IRE) and Microwave Ablation (MWA) of Hepatocellular Carcinoma (HCC) Using Iodine Quantification in Dual Energy Computed Tomography (DECT)

Early detection of local tumor progression (LTP) after irreversible electroporation (IRE) and microwave ablation (MWA) of hepatocellular carcinoma (HCC) remains challenging. The goal of this study was to identify cases with insufficient ablation and prevent HCC recurrencies by measuring iodine uptake using dual-energy computed tomography (DECT). In 54 HCC-patients, the volumetric iodine concentration (VIC) of the central and peripheral ablation area was evaluated by DECT within 24 h after IRE or MWA. Follow-up was performed with CT and/or MRI at 6 weeks, 3, 6, 9, and 12 months, respectively. In both groups, LTP was solely detected in the peripheral area (IRE: n = 4; MWA: n = 4) and LTP patients showed significantly higher VIC values in the peripheral zone than patients without LTP (IRE: * p = 0.0005; MWA: * p = 0.000). In IRE-LTP patients, no significant difference between the VIC values of non-ablated liver tissue and the peripheral zone was detected (p = 0.155). The peripheral zones of IRE patients without LTP (* p = 0.000) and MWA patients, irrespective of the presence of LTP (LTP: * p = 0.005; without LTP: * p = 0.000), showed significantly lower VIC values than non-ablated liver parenchyma. Higher BCLC tumor stages were indicative for LTP (* p = 0.008). The study suggests that elevated iodine uptake in the peripheral ablation zone could help identify LTP after IRE and MWA of HCC

Changes in gadoxetic-acid-enhanced MR imaging during the first year after irreversible electroporation of malignant hepatic tumors

Purpose To evaluate the appearance and size of ablation zones in gadoxetic-acid-enhanced magnetic resonance imaging (MRI) during the first year after irreversible electroporation (IRE) of primary or secondary hepatic malignancies and to investigate potential correlations to clinical features. Material and methods The MRI-appearance of the ablation area was assessed 1-3 days, 6 weeks, 3 months, 6 months, 9 months and 1 year after IRE. The size of the ablation zone and signal intensities of each follow-up control were compared. Moreover, relationships between clinical features and the MRI-appearance of the ablation area 1-3 days after IRE were analyzed. Results The ablation zone size decreased from 5.6 +/- 1.4 cm (1-3 days) to 3.7 +/- 1.2 cm (1 year). A significant decrease of central hypointensities was observed in T2-blade- (3 months), T2 haste- (6 weeks; 3 months; 6 months; 1 year), T1 arterial phase- (3 months; 1 year), and diffusion-sequences (6 weeks; 3 months; 6 months; 9 months; 1 year). The unenhanced T1-sequences showed significantly increasing central hypointensities (6 weeks; 3 months; 6 months; 9 months; 1 year). Significantly increasing peripheral hypointensities were detected in T1 arterial phase- (3 months; 6 months; 9 months; 1 year) and in T1 portal venous phase-sequences (6 weeks; 3 months; 6 months; 9 months; 1 year). Peripheral hypointensities of unenhanced T1-sequences decreased significantly 1 year after IRE. 1-3 days after IRE central T1 portal venous hypo- or isointensities were detected significantly more often than hyperintensities, if more than 3 IRE electrodes were used. Conclusion Hepatic IRE results in continuous reduction of ablation zone size during the first postinterventional year. In addition to centrally decreasing T1-signal and almost steadily increasing signal in the enhanced T2 haste-, diffusion- and T1 arterial phase-sequences, there is a trend toward long-term decreasing T1 arterial- and portal venous MRI-signal intensity of the peripheral ablation area, probably representing a region of reversible electroporation

Necessity of Immediate MRI Imaging in the Acute Care of Severely Injured Patients

Background and Objectives: The standard diagnostic procedure for a patient with a suspected polytrauma injury is computed tomography (CT). In individual cases, however, extended acute imaging using magnetic resonance imaging (MRI) can provide valuable and therapy-relevant information. The aim of our cohort study was to find such cases and to describe their characteristics in order to be able to give possible recommendations for MRI application in acute trauma situations. Materials and Methods: In the study period from 2015–2019, an evaluation of the imaging performed on polytrauma patients was carried out. The specific diagnostic and therapeutic criteria of the MRI group were further defined. Results: In total, 580 patients with an ISS ≥16 (injury severity score) were included in the study. Of these 580 patients, 568 patients received a CT scan and 12 patients an MRI scan as part of the initial diagnostic. Altogether, 66.67% of the MRIs took place outside of regular service hours. The main findings for MRI indications were neurological abnormalities with a focus on myelon injuries. Further MRI examinations were performed to rule out vascular injuries. All in all, 58.3% of the MRIs performed resulted in modified therapeutic strategies afterward. Conclusions: MRI in the context of acute diagnostic of a severely injured patient will likely remain reserved for special indications in the future. However, maximum care hospitals with a high flow of severely injured patients should provide 24/7 MR imaging to ensure the best possible care, especially in neurological and blunt vascular injuries

Evaluation of Alterations to Bile Ducts and Laboratory Values During the First 3 Months After Irreversible Electroporation of Malignant Hepatic Tumors

Purpose: To assess the incidence and evolution of biliary alterations adjacent to the ablation area in patients with hepatic malignancies during the first 3 months after percutaneous irreversible electroporation (IRE) and to investigate associated changes in laboratory values. Material and Methods: Bile ducts located within a <1.0 cm radius of the ablation zone were analyzed in 45 patients by preinterventional and postinterventional MRI (1-3 days, 6 weeks, and 3 months after IRE). Moreover, levels of alkaline phosphatase (AP) and serum bilirubin (SB) were examined for evidence of bile duct injury. Biliary alterations and the presence of postinterventional-elevated laboratory levels were correlated with features of the lesions, patients, ablation procedures, and laboratory values. Results: A total of 80 bile ducts were located within a 1.0 cm radius of the ablation zone: 59 were encased, 16 were abutting and 5 were located within a radius of 0.1-1.0 cm of the ablation area. In total, 38 biliary injuries (narrowing, n=22; dilatation, n=14; biloma, n=2) were detected, 3 cases of narrowing occurred for the first time 6 weeks and 3 months after IRE, 21 alterations (dilatation: n=9; narrowing; n=10; biloma: n=2) had resolved during the first 6 weeks, 1 alteration (dilatation: n=1) had resolved by the last follow-up control. Three months after IRE, 19 patients showed elevated levels of AP, whereas SB levels were increased in 10 cases. No significant association between biliary alterations or postinterventional-elevated laboratory values and the investigated characteristics of lesions, patients, ablation procedures or laboratory values could be proven. Conclusion: Different alterations of bile ducts adjacent to an IRE ablation zone are common, of which dilatation and especially narrowing commonly represent a long-term complication after IRE. Moreover, a definite correlation between the frequently observed prolonged post-ablative elevation of AP- and SB-levels and the postinterventional biliary alterations could not be proven

The Salmonella enterica Serotype Typhimurium Effector Proteins SipA, SopA, SopB, SopD, and SopE2 Act in Concert To Induce Diarrhea in Calves

Salmonella enterica serotype Typhimurium requires a functional type III secretion system encoded by Salmonella pathogenicity island 1 (SPI1) to cause diarrhea. We investigated the role of genes encoding secreted target proteins of the SPI1-associated type III secretion system for enteropathogenicity in calves. Salmonella serotype Typhimurium strains having mutations in sptP, avrA, sspH1, or slrP induced fluid secretion in the bovine ligated ileal loop model at levels similar to that of the wild type. In contrast, mutations in sipA, sopA, sopB, sopD, or sopE2 significantly reduced fluid accumulation in bovine ligated ileal loops at 8 h postinfection. A strain carrying mutations in sipA, sopA, sopB, sopD, and sopE2 (sipA sopABDE2 mutant) caused the same level of fluid accumulation in bovine ligated ileal loops as a strain carrying a mutation in sipB, a SPI1 gene required for the translocation of effector proteins into host cells. A positive correlation was observed between the severity of histopathological lesions detected in the ileal mucosa and the levels of fluid accumulation induced by the different mutants. After oral infection of calves, the Salmonella serotype Typhimurium sipAsopABDE2 mutant caused only mild diarrhea and was more strongly attenuated than strains having only single mutations. These data demonstrate that SipA, SopA, SopB, SopD, and SopE2 are major virulence factors responsible for diarrhea during Salmonella serotype Typhimurium infection of calves

Stress, the cortisol awakening response and cognitive function

There is evidence that stress-induced disruption of the circadian rhythm of cortisol secretion, has negative consequences for brain health. The cortisol awakening response (CAR) is the most prominent and dynamic aspect of this rhythm. It has complex regulatory mechanisms making it distinct from the rest of the cortisol circadian rhythm, and is frequently investigated as a biomarker of stress and potential intermediary between stress and impaired brain function. Despite this, the precise function of the CAR within the healthy cortisol circadian rhythm remains poorly understood. Cortisol is a powerful hormone known to influence cognition in multiple and complex ways. Studies of the CAR and cognitive function have used varied methodological approaches which have produced similarly varied findings. The present review considers the accumulating evidence linking stress, attenuation of the CAR and reduced cognitive function, and seeks to contextualize the many findings to study populations, cognitive measures, and CAR methodologies employed. Associations between the CAR and both memory and executive functions are discussed in relation to its potential role as a neuroendocrine time of day signal that synchronizes peripheral clocks throughout the brain to enable optimum function, and recommendations for future research are provided