Improved visualization of hepatic tumors in magnetic resonance-guided thermoablation using T1-inversion-recovery imaging with variable inversion time.

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.

MRI-guided percutaneous thermoablation as first-line treatment of recurrent hepatic malignancies following hepatic resection: single center long-term experience.

PURPOSE: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy.

PURPOSE: 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). PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Activity-dependent release of transforming growth factor-beta in a neuronal network in vitro.

For neurotrophins and also for members of the transforming growth factor beta (TGF-beta) 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-beta in vitro using mouse primary hippocampal neurons at embryonic day E16.5 as model. We show that neuronal activity regulates TGF-beta release and TGF-beta expression in vitro. Treatment of the cultures with KCl, 3-veratroylveracevine (veratridine), glutamate or carbamylcholine chloride (carbachol) increased the levels of secreted TGF-beta, as assessed by the MLEC/plasminogen activator inhibitor (PAI)-luciferase-assay, whereas TGF-beta 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-beta2 and TGF-beta3 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-beta inducible early gene (Tieg1) expression, demonstrating that activity-dependent released TGF-beta may exert autocrine actions and thereby activate the TGF-beta-dependent signaling pathway. Together, these results suggest an activity-dependent release and gene transcription of TGF-beta from mouse hippocampal neurons in vitro as well as subsequent autocrine functions of the released TGF-beta within the hippocampal network.

[Malignant gastrointestinal stromal tumor (GIST) of the papilla vateri. A rare tumor entity]. / Maligner gastrointestinaler Stromatumor (GIST) der Papilla vateri. Eine seltene Tumorentität.

We present the case report of a 68-year-old female patient who had a malignant gastrointestinal stromal tumor of the papilla of Vater. The abdominal CT showed a coin-shaped lesion in the liver (segment VIII). Intraoperative rapid histological examination detected an old parasitic hepatic cyst. To exclude metastasis, we performed duodenopancreatectomy with curative intention. The postoperative course was without complications and neither chemotherapy nor other adjunct treatment was necessary. Because of heterogeneity, the different localization, and in this case the rare localization, surgery of gastrointestinal stromal tumors is difficult. However, we adhered to oncological and therapeutic standards of surgery for papillary carcinoma. This case is discussed based on a review of the literature. However, until now there has been no case report of gastrointestinal stromal tumor of the papilla of Vater in the literature.

High mobility group protein HMGA1 expression in breast cancer reveals a positive correlation with tumour grade.

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.

[Metachronous second carcinoma after curative treatment of cholangiocarcinoma by duodenopancreatectomy]. / Metachrones Zweitcarcinom nach kurativer Behandlung eines Cholangiocarcinoms durch Duodenopankreatektomie.

In comparison to pancreatic cancer, extrahepatic cholangiocarcinoma has a better prognosis and a higher resection rate, but it is tainted with the occurrence of metachronic tumors. Metachronic tumors of the female genitalia are described in the literature, but metachronic gastric cancer after curative treatment of cholangiocacinoma is also possible.

Two cases of fibrocystic breast disease with polysomy 18 as the sole clonal cytogenetic abnormality.

In the present study, we describe the occurrence of numerical alterations of chromosome 18 in two cases of benign fibrous/fibrocystic tumors of the breast, both of which were studied by conventional cytogenetic investigations and one of which was additionally tested by fluorescence in situ hybridization with the use of an alphoid centromeric probe specific for chromosome 18. Case 1 showed a tetrasomy 18 in 2 of 33 metaphases as the only clonal chromosomal aberration. Case 2 revealed both trisomy and tetrasomy 18 as clonal alterations in metaphases and interphase nuclei.

Fluorescence in situ hybridization studies on breast tumor samples for distinguishing between different subsets of breast cancer.

OBJECTIVES: To evaluate fluorescence in situ hybridization for distinguishing between malignant and benign breast tumors and determining genetic subgroups of breast cancers. STUDY DESIGN: Touch preparations from 94 surgically removed breast tumors (17 benign and 77 malignant) were hybridized with a DNA probe specific for centromeric DNA sequences of chromosome 1. Twenty samples were additionally hybridized with a chromosome 9-specific probe. RESULTS: We investigated the heterogeneity of the cell populations on the basis of the number of signals per nucleus. All benign tumors showed two signals per nucleus. In contrast, carcinomas revealed a broad spectrum of hybridization patterns. Some showed almost exclusively two signals per nucleus, and others exceeded four signals. CONCLUSION: The hybridization patterns of individual tumors can be used for defining different subsets of breast cancer. The results may have prognostic impact, leading to "molecular-cytogenetic grading" of breast cancer.

Trisomy 8 and 18 as frequent clonal and single-cell aberrations in 185 primary breast carcinomas.

For cytogenetic investigations short-term cultures of 185 breast carcinomas (135 invasive ductal, 21 invasive lobular, 12 invasive ductal with intraductal components, seven heterogeneous, six intraductal, four invasive ductal and lobular) were prepared. Cytogenetic examinations revealed clonal abnormalities in 39 cases with a predominance of simple numerical chromosome changes, i.e., trisomies of chromosomes 7, 8, and 18. One hundred forty-six tumors did not show clonal abnormalities, but single-cell aberrations other than monosomies occurred in 79 of these tumors. Compared to cells of epithelial hyperplasia of the breast, amniotic fluid cells, and cells from pleomorphic adenomas cultivated using the same medium, the frequency of single-cell trisomies was significantly higher. Trisomy 8 was not only found as a clonal aberration in 10 cases but was also the most frequent non-clonal aberration. Trisomy 7 and 18 were also frequent clonal as well as non-clonal cytogenetic deviations.