Objectives
In magnetic resonance (MR)–guided interventions, visualization of hepatic lesions may be difficult using standard unenhanced T1-weighted gradient-echo volume-interpolated breath-hold ...(VIBE) sequence due to low contrast. Inversion recovery (IR) imaging may have the potential to improve visualization without the necessity to apply contrast agent.
Methods
Forty-four patients (mean age 64 years, female 33%) scheduled for MR-guided thermoablation due to liver malignancies (hepatocellular carcinoma or metastases) were prospectively included in this study between March 2020 and April 2022. Fifty-one liver lesions were intra-procedurally characterized before treatment. Unenhanced T1-VIBE was acquired as part of the standard imaging protocol. Additionally, T1-modified look-locker images were acquired with eight different inversion times (TI) between 148 and 1743 ms. Lesion-to-liver contrast (LLC) was compared between T1-VIBE and IR images for each TI. T1 relaxation times for liver lesions and liver parenchyma were calculated.
Results
Mean LLC in T1-VIBE sequence was 0.3 ± 0.1. In IR images, LLC was highest at TI 228 ms (1.04 ± 1.1) and significantly higher compared to T1-VIBE (
p
< 0.001). In subgroup analysis, lesions of colorectal carcinoma showed the highest LLC at 228 ms (1.14 ± 1.4), and hepatocellular carcinoma showed the highest LLC at 548 ms (1.06 ± 1.16). T1-relaxation times in liver lesions were higher compared to the adjacent liver parenchyma (1184 ± 456 vs. 654 ± 96 ms,
p
< 0.001).
Conclusions
IR imaging is promising to provide improved visualization during unenhanced MR-guided liver interventions compared to standard T1-VIBE sequence when using specific TI. Low TI between 150 and 230 ms yields the highest contrast between liver parenchyma and malignant liver lesions.
Clinical relevance statement
Improved visualization of hepatic lesions during MR-guided percutaneous interventions using inversion recovery imaging without the necessity to apply contrast agent.
Key points
• Inversion recovery imaging is promising to provide improved visualization of liver lesions in unenhanced MRI.
• Planning and guidance during MR-guided interventions in the liver can be performed with greater confidence without necessity to apply contrast agent.
• Low TI between 150 and 230 ms yields the highest contrast between liver parenchyma and malignant liver lesions.
Hepatic recurrence of liver malignancies is a leading problem in patients after liver resection with curative intention. Thermoablation is a promising treatment approach for patients after hepatic ...resection, especially in liver-limited conditions. This study aimed to investigate safety, survival, and local tumor control rates of MRI-guided percutaneous thermoablation of recurrent hepatic malignancies following hepatic resection.
Data from patients with primary or secondary hepatic malignancies treated between 2004 and 2018 with MRI-guided percutaneous thermoablation of hepatic recurrence after prior hepatic resection were retrospectively analyzed. Disease-free survival and overall survival rates were calculated using the Kaplan-Meier method.
A total of 57 patients with hepatic recurrence (mean tumor size = 18.9 ± 9.1 mm) of colorectal cancer liver metastases (n = 27), hepatocellular carcinoma (n = 17), intrahepatic recurrence of cholangiocellular carcinoma (n = 9), or other primary malignant tumor entities (n = 4) were treated once or several times with MR-guided percutaneous radiofrequency (n = 52) or microwave ablation (n = 5) (range: 1-4 times). Disease progression occurred due to local recurrence at the ablation site in nine patients (15.8%), non-local hepatic recurrence in 33 patients (57.9%), and distant malignancy in 18 patients (31.6%). The median overall survival for the total cohort was 40 months and 49 months for the colorectal cancer group, with a 5-year overall survival rate of 40.7 and 42.5%, respectively. The median disease-free survival was 10 months for both the total cohort and the colorectal cancer group with a 5-year disease-free survival rate of 15.1 and 14.8%, respectively. The mean follow-up time was 39.6 ± 35.7 months.
MR-guided thermoablation is an effective and safe approach in the treatment of hepatic recurrences in liver-limited conditions and can achieve long-term survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine whether tumor grade, molecular subtype and hypoxia predict response to hypofractionated versus standard radiotherapy (RT) following breast-conserving surgery (BCS) for node-negative ...breast cancer in a randomized controlled trial (RCT).
Formalin-fixed paraffin-embedded (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology review and assessment of tumor grade using the Nottingham grading system was carried out. Tumors were classified by molecular subtype as luminal A, luminal B, HER2 enriched, basal-like or unclassified using a six-biomarker panel; ER, PR, HER-2, Ki67, CK5/6 and EGFR. Tumors were also classified as hypoxic based on the expression of HIF1α, CAIX or GLUT-1. The primary end point was local recurrence (LR).
Median follow-up was 12 years. In the multivariable Cox model, molecular subtype was the only factor predictive of LR, the 10-year cumulative incidence was 4.5% for luminal A and basal-like, 7.9% for luminal B and 16.9% for HER-2 enriched tumors (P < 0.01). Tumor grade, molecular subtype or hypoxia did not predict response to hypofractionation.
In women enrolled in the HWBI trial following BCS tumor molecular subtype predicted LR. However tumor grade, molecular subtype and hypoxia did not predict response to hypofractionation suggesting that patients with node-negative breast tumors of all grades and molecular subtypes may be safely treated with hypofractionated RT regimens.
Abstract For neurotrophins and also for members of the transforming growth factor beta (TGF-β) family an activity-dependent regulation of synthesis and release has been proposed. Together with the ...observation that the secretion of neurotransmitters is initiated by neurotrophic factors, it is reasonable to assume that they might act as retrograde modulators enhancing the efficacy and stabilization of synapses. In the present study, we have tested this hypothesis and studied the release and regulation of TGF-β in vitro using mouse primary hippocampal neurons at embryonic day E16.5 as model. We show that neuronal activity regulates TGF-β release and TGF-β expression in vitro . Treatment of the cultures with KCl, 3-veratroylveracevine (veratridine), glutamate or carbamylcholine chloride (carbachol) increased the levels of secreted TGF-β, as assessed by the MLEC/plasminogen activator inhibitor (PAI)–luciferase-assay, whereas TGF-β release stimulated by KCl or veratridine was reduced in the presence of tetrodotoxin or 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). In addition, application of glutamate significantly upregulated expression of TGF-β2 and TGF-β3 in the culture. Notably, KCl stimulation caused Smad (composite term from SMA ( C. elegans ) and MAD=mothers against dpp ( Drosophila )) translocation into the nucleus and upregulated TGF-β inducible early gene (Tieg1) expression, demonstrating that activity-dependent released TGF-β may exert autocrine actions and thereby activate the TGF-β-dependent signaling pathway. Together, these results suggest an activity-dependent release and gene transcription of TGF-β from mouse hippocampal neurons in vitro as well as subsequent autocrine functions of the released TGF-β within the hippocampal network.
Members of the HMGA protein (high mobility group protein A) family act as master switches of the chromatin structure by bending DNA and thus modulating the formation of transcription factor complexes ...of a number of target genes. Accordingly, HMGA proteins have been shown to be associated with the development and/or progression of a variety of benign and malignant tumours. Nevertheless, the HMGA1 expression studies published so far have not included primary breast cancer samples. In this study we have investigated the HMGA1 expression patterns in a series of 170 breast cancer samples by immunohistochemistry. We have found a strong variation in HMGA1 expression between the tumours. Based on an immunoreactive score (IRS) 14.1% of the tumour samples were scored to IRS 8-12 (strong positivity for HMGA1), 24.7% were scored to IRS 4-6 (moderate positivity), 25.3% were scored to IRS 1-3 (weak positivity), and 35.9% showed no positivity at all. Immunoreaction could be detected in all histological types of breast cancers analysed with the exception of invasive papillary and cribriform carcinoma. Statistical analysis revealed a strong correlation between tumour grade and HMGA1 expression (rs=0.3516, p<0.0001). Thus, the HMGA1 expression level can be considered a potential prognostic marker for breast cancer.
The tetracycline-controlled transcription system has become one of the most potent systems for experimental manipulations of transcription levels in vivo. Here we report on rtTA variants, which were ...generated by combining the existing positively regulated Tet repressor domains of rtTA and rtTA-M2 with a modified and multimerized minimal transactivation domain from VP16 (L-domain). A transactivator with multimerized L-domains shows drastically reduced background activity and enhanced transcriptional activation on different tetracycline-responsive promoters. The new rtTA variants require higher doses of doxycycline and display a more linear dose–response curve than the original rtTA or rtTA-M2 proteins.
Background: The aim of this study was to review the role
of the pathologist in mammography screening. Patients
and Methods: The first German mammography screening
project was undertaken in Bremen in ...June 2001.
Women between the ages of 50 and 69 were offered
mammographic assessment. Suspicious findings were
followed up by a stereotactic core biopsy or vacuum-assisted
core biopsy. The tissue was examined at the Department
of Pathology in Bremen as well as at the Section
of Breast Pathology at the University Münster. Each
case was discussed in a multidisciplinary board. The
core biopsies were classified according to the 5-point
scale of the internationial guidelines. Results: Biopsies
were obtained from 402 women within the first 2 years
of the screening project. Of these, 47% were assigned to
group B5 (malignant), 44% were categorized in group B2
(benign) while 1% was classified in group B1 (regular
breast tissue, unsatisfactory) and 8% were assigned to
the group B3/B4 (lesion of uncertain malignant potential /
suspicious for malignancy). The discrepancies in 10% of
the cases centered on papillary lesions, flat epithelial
atypia (FEA) and atypical ductal hyperplasia (ADH). Conclusion:
In clearly defined lesions the agreement of the
histological findings of independent pathologists is very
high. In unclear lesions it should be raised. In addition,
close cooperation between clinicians, radiologists and
pathologists is critical.
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