A comparative study assessing the efficacy and safety of radiofrequency ablation versus surgical treatment for osteoid osteoma: retrospective analysis in a single institution.

OBJECTIVE: We aim to evaluate the efficacy of CT-guided percutaneous radiofrequency ablation (RFA) and surgical treatment in osteoid osteoma (OO) treated at the Medical University of Graz. MATERIALS AND METHODS: In a single-institution study, we analysed data from January 2005 to January 2021 of patients with histological/radiological diagnosis of OO. CT and MRI scans were reviewed for typical findings. Means (with SD) and medians (with IQR) were reported for normally and non-normally distributed variables. Differences between groups were assessed using chi-squared tests and t-tests. RESULTS: One hundred nineteen patients (mean age: 21.6 ± 10.9 years; 63.9% males) with confirmed OO were retrospectively evaluated. 73 and 43 patients underwent RFA and surgery, respectively. In three cases, RFA combined with surgery was performed. Pre-intervention, 103 patients (88.8%) had undergone CT, and 101 had an MRI (87.1%). The nidus was confirmed in 82.5% of cases with CTs (85/103) and 63.4% with MRIs (64/101). The majority of nidi were located cortically (n = 96; 82.8%), most frequently in the femur (38 patients, 33.3%) with a median size of 8.0 mm (IQR: 5.0-12.0 mm). Median symptom duration before treatment was 6.0 (IQR: 4.0-13.0) months. The complication rate was 12.1% (14/116; 15.1% RFA vs. 7.0% surgery; p = 0.196). In total, 11.2% of patients had persistent symptoms after one week with clinical success rates of RFA and surgery, 86.3% and 90.7% (p = 0.647), respectively. CONCLUSION: Compared to surgical treatment, CT-guided percutaneous RFA is a safe, minimally invasive, reliable, and efficient treatment option for OO. CRITICAL RELEVANCE STATEMENT: This article critically assesses the diagnosis and treatment of osteoid osteoma, emphasising accurate imaging, and detailing a non-invasive option for effective management. KEY POINTS: • This study analyses 116 cases of OO at one institution, focusing on symptom persistence, recurrence in short-term follow-up, and complications in two study groups. • Surgery showed higher, though not statistically significant, success despite comparable symptom persistence; CT displayed typical OO features more than MRI, regardless of the intramedullary, cortical and subperiosteal location as well as the site of the affected bone. • CT-guided RFA is an effective therapeutic alternative for OO compared to surgical intervention. In case of atypical OO appearance, RFA is not the first-line treatment.

Perfusion Computed Tomography in Rectal Carcinoma: Influence of Optimization of the Patlak Range on Calculation of Equivalent Blood Volume and Flow Extraction.

PURPOSE: The aim of the study is to assess the influence of manual adjustment of the Patlak range in computed tomography (CT) perfusion analysis of rectal carcinoma compared with default range of the perfusion software. METHODS: This study was approved by the institutional review board and informed consent was obtained. Twenty-one patients (12 male, 9 female; mean age ± SD, 59 ± 11 years) with rectal cancer were included and underwent perfusion CT before preoperative chemoradiotherapy. Equivalent blood volume (BV) and flow-extraction (FE) were calculated using the Patlak plot model. Two perfusion sets were calculated per patient, a perfusion set using the default setting as provided by the software (dBV, dFE) and an optimized perfusion set after manual adaption of the Patlak range (aBV, aFE), which was limited to the intravascular space clearance of contrast to the extravascular space. Perfusion values calculated with both methods were compared for significance in differences using the Wilcoxon test. A P value of 0.05 or less was defined as statistically significant. RESULTS: Adjustment of the Patlak range statistically significantly influenced BV and FE calculation. Median dBV was 23.2 mL/100 mL (interquartile range [IQR], 12.1 mL/100 mL), whereas median aBV was 20.3 mL/100 mL (IQR, 10.9 mL/100 mL). The difference in BV was statistically significant ( P = 0.021). Median dFE was 8.3 mL/min/100 mL (IQR, 4.7 mL/min/100 mL), whereas median aFE was 15.4 mL/min/100 mL (IQR, 5.8 mL/min/100 mL). The difference in FE was statistically significant ( P < 0.001). CONCLUSIONS: Our findings indicate that in perfusion CT of rectal carcinoma, adjustment of the Patlak range may significantly influence BV and FE compared with default setting of the software. This may contribute to standardization in the use of this technique for functional imaging of rectal cancer.

Three dimensional computed tomography texture analysis of pulmonary lesions: Does radiomics allow differentiation between carcinoma, neuroendocrine tumor and organizing pneumonia?

PURPOSE: To investigate whether CT texture analysis allows differentiation between adenocarcinomas, squamous cell carcinomas, carcinoids, small cell lung cancers and organizing pneumonia and between carcinomas and neuroendocrine tumors. METHOD: This retrospective study included patients 133 patients (30 patients with organizing pneumonia, 30 patients with adenocarcinoma, 30 patients with squamous cell carcinoma, 23 patients with small cell lung cancer, 20 patients with carcinoid), who underwent CT-guided biopsy of the lung and had a corresponding histopathologic diagnosis. Pulmonary lesions were segmented in consensus by two radiologists with and without a threshold of -50HU in three dimensions. Groupwise comparisons were performed to assess for differences between all five above-listed entities and between carcinomas and neuroendocrine tumors. RESULTS: Pairwise comparisons of the five entities revealed 53 statistically significant texture features when using no HU-threshold and 6 statistically significant features with a threshold of -50HU. The largest AUC (0.818 [95%CI 0.706-0.930]) was found for the feature wavelet-HHH_glszm_SmallAreaEmphasis for discrimination of carcinoid from the other entities when using no HU-threshold. In differentiating neuroendocrine tumors from carcinomas, 173 parameters proved statistically significant when using no HU threshold versus 52 parameters when using a -50HU-threshold. The largest AUC (0.810 [95%CI 0.728-0,893]) was found for the parameter original_glcm_Correlation for discrimination of neuroendocrine tumors from carcinomas when using no HU-threshold. CONCLUSIONS: CT texture analysis revealed features that differed significantly between malignant pulmonary lesions and organizing pneumonia and between carcinomas and neuroendocrine tumors of the lung. Applying a HU-threshold for segmentation substantially influenced the results of texture analysis.

CT texture analysis reliability in pulmonary lesions: the influence of 3D vs. 2D lesion segmentation and volume definition by a Hounsfield-unit threshold.

OBJECTIVE: Reproducibility problems are a known limitation of radiomics. The segmentation of the target lesion plays a critical role in texture analysis variability. This study's aim was to compare the interobserver reliability of manual 2D vs. 3D lung lesion segmentation with and without pre-definition of the volume using a threshold of - 50 HU. METHODS: Seventy-five patients with histopathologically proven lung lesions (15 patients each with adenocarcinoma, squamous cell carcinoma, small cell lung cancer, carcinoid, and organizing pneumonia) who underwent an unenhanced CT scan of the chest were included. Three radiologists independently segmented each lesion manually in 3D and 2D with and without pre-segmentation volume definition by a HU threshold, and shape parameters and original, Laplacian of Gaussian-filtered, and wavelet-based texture features were derived. To assess interobserver reliability and identify the most robust texture features, intraclass correlation coefficients (ICCs) for different segmentation settings were calculated. RESULTS: Shape parameters had high reliability (64-79% had excellent and good ICCs). Texture features had weak reliability levels, with the highest ICCs (38% excellent or good) found for original features in 3D segmentation without the use of a HU threshold. A small proportion (4.3-11.5%) of texture features had excellent or good ICC values at all segmentation settings. CONCLUSION: Interobserver reliability of texture features from CT scans of a heterogeneous collection of manually segmented lung lesions was low with a small proportion of features demonstrating high reliability independent of the segmentation settings. These results indicate a limited applicability of texture analysis and the need to define robust texture features in patients with lung lesions. KEY POINTS: • Our study showed a low reproducibility of texture features when 3 radiologists independently segmented lung lesions in CT images, which highlights a serious limitation of texture analysis. • Interobserver reliability of texture features was low regardless of whether the lesion was segmented in 2D and 3D with or without a HU threshold. • In contrast to texture features, shape parameters showed a high interobserver reliability when lesions were segmented in 2D vs. 3D with and without a HU threshold of - 50.

18F-FDG PET/CT in Primary Mesothelioma of the Liver.

ABSTRACT: Primary malignant mesothelioma is a rarity among malignant liver tumors. We present the case of a 48-year-old woman presenting with increasing upper abdominal discomfort and inappetence accompanied by a weight loss of approximately 10 kg. CT and MRI revealed a highly suspicious mass lesion in the liver. 18F-FDG PET/CT performed for staging showed a pathological 18F-FDG uptake of the known liver tumor. Histology and immunohistochemistry indicated mesothelioma of the liver. Herein we present a rare case of primary mesothelioma in the liver with CT, MRI, and 18F-FDG PET/CT.

Non-colorectal liver metastases: A review of interventional and surgical treatment modalities.

Liver metastases (LM) occur in up to 90% either simultaneously with the diagnosis of the primary tumor or at a later time-point. While resection of colorectal LM and resection or transplantation of neuroendocrine LM is part of a standard therapy with a 5-year patient survival of up to 80%, resection of non-colorectal and non-neuroendocrine LM is still discussed controversially. The reason for it is the significantly lower survival benefit of all different tumor entities depending on the biological aggressiveness of the tumor. Randomized controlled trials are lacking. However, reviews of case series with ≥100 liver resections are available. They show a 5-year patient survival of up to 42% compared to only <5% in patients without treatment. Risk factors for poor survival include the type of primary tumor, a short interval between resection of the primary tumor and liver resection, extrahepatic manifestation of the tumor, number and size of the LM, and extent of liver resection. Overall, it has recently been shown that a good patient selection, the technical advances in surgical therapy and the use of a risk score to predict the prognosis lead to a significantly better outcome so that it is no longer justified not to offer liver resection to patients with non-colorectal, non- endocrine LM. Since modern therapy of LM is multimodal, the optimal therapeutic approach is decided individually by a multidisciplinary team consisting of visceral surgeons, oncologists, interventional radiologists and radiologists as part of a tumor board.

Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients.

Objective: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. Methods: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. Results: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. Conclusion: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients.

Non-contrast-enhanced CT texture analysis of primary and metastatic pancreatic ductal adenocarcinomas: value in assessment of histopathological grade and differences between primary and metastatic lesions.

PURPOSE: To evaluate the utility of non-contrast-enhanced CT texture analysis (CTTA) for predicting the histopathological differentiation of pancreatic ductal adenocarcinomas (PDAC) and to compare non-contrast-enhanced CTTA texture features between primary PDAC and hepatic metastases of PDAC. METHODS: This retrospective study included 120 patients with histopathologically confirmed PDAC. Sixty-five patients underwent CT-guided biopsy of primary PDAC, while 55 patients underwent CT-guided biopsy of hepatic PDAC metastasis. All lesions were segmented in non-contrast-enhanced CT scans for CTTA based on histogram analysis, co-occurrence matrix, and run-length matrix. Statistical analysis was conducted for 372 texture features using Mann-Whitney U test, Bonferroni-Holm correction, and receiver operating characteristic (ROC) analysis. A p value < 0.05 was considered statistically significant. RESULTS: Three features were identified that differed significantly between histopathological G2 and G3 primary tumors. Of these, "low gray-level zone emphasis" yielded the largest AUC (0.87 ± 0.04), reaching a sensitivity and specificity of 0.76 and 0.83, respectively, when a cut-off value of 0.482 was applied. Fifty-four features differed significantly between primary and hepatic metastatic PDAC. CONCLUSION: Non-contrast-enhanced CTTA of PDAC identified differences in texture features between primary G2 and G3 tumors that could be used for non-invasive tumor assessment. Extensive differences between the features of primary and metastatic PDAC on CTTA suggest differences in tumor microenvironment.

Secondary sclerosing cholangitis in a young COVID-19 patient resulting in death: A case report.

BACKGROUND: With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 in Wuhan, China, liver injury in patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has been regularly reported in the literature. There are a growing number of publications describing the occurrence of secondary sclerosing cholangitis (SSC) after SARS-CoV-2 infection in various cases. We present a case of sudden onset SSC in a critically ill patient (SSC-CIP) following COVID-19 infection who was previously healthy. CASE SUMMARY: A 33-year old female patient was admitted to our University Hospital due to increasing shortness of breath. A prior rapid antigen test showed a positive result for SARS-CoV-2. The patient had no known preexisting conditions. With rapidly increasing severe hypoxemia she required endotracheal intubation and developed the need for veno-venous extracorporeal membrane oxygenation in a setting of acute respiratory distress syndrome. During the patient´s 154-d stay in the intensive care unit and other hospital wards she underwent hemodialysis and extended polypharmaceutical treatment. With increasing liver enzymes and the development of signs of cholangiopathy on magnetic resonance cholangiopancreatography (MRCP) as well as endoscopic retrograde cholangiopancreatography (ERCP), the clinical setting was suggestive of SSC. At an interdisciplinary meeting, the possibility of orthotopic liver transplantation and additional kidney transplantation was discussed due to the constant need for hemodialysis. Following a deterioration in her general health and impaired respiratory function with a reduced chance of successful surgery and rehabilitation, the plan for transplantation was discarded. The patient passed away due to multiorgan failure. CONCLUSION: SSC-CIP seems to be a rare but serious complication in patients with SARS-CoV-2 infection, of which treating physicians should be aware. Imaging with MRCP and/or ERCP seems to be indicated and a valid method for early diagnosis. Further studies on the effects of early and late SSC in (post-) COVID-19 patients needs to be performed.

Liver Transplantation in Malignancies: A Comprehensive and Systematic Review on Oncological Outcome.

INTRODUCTION: Liver transplantation (LT) is today's standard treatment for both end-stage liver disease and tumors; however, suitable grafts for LT are a scarce resource and outcome after LT is highly dependent on its underlying indication. Thus, patients must be carefully selected to optimize the number of life years gained per graft. This comprehensive and systematic review critically reflects the most recently published oncological outcome data after LT in malignancies based on the preoperative radiological findings. METHODS: A systematic literature search was conducted to detect preferentially most recent high-volume series or large database analysis on oncological outcomes after LT for both primary liver cancer and liver metastases between January 1, 2019, and November 14, 2020. A comprehensive review on the radiological assessment of the reviewed liver malignancies is included and its preoperative value for an outcome-driven indication reflected. RESULTS: Twenty most recent high-volume or relevant studies including a total number of 2,521 patients were identified including 4, 4, 4, 4, 3, and 1 publications on oncological outcome after LT for hepatocellular carcinoma, cholangiocellular carcinoma, hepatic epitheloid hemangioendothelioma, hepatoblastoma, and both metastatic neuroendocrine tumors and colorectal cancer, respectively. The overall survival is comparable to patients without tumors if patients with malignancies are well selected for LT; however, this is highly dependent on tumor entity, tumor stage, and both neoadjuvant and concomitant treatment. DISCUSSION/CONCLUSION: LT is a promising option for better survival in patients with malignant liver tumors in selected patients; however, the indication must be critically discussed prior to LT in every single case in the context of organ shortage.

Circulating Tumor DNA as a Marker for Treatment Response in Metastatic Melanoma Patients Using Next-Generation Sequencing-A Prospective Feasibility Study.

We prospectively performed a longitudinal analysis of circulating tumor DNA (ctDNA) from 149 plasma samples and CT scans in Stage III and IV metastatic melanoma patients (n = 20) treated with targeted agents or immunotherapy using two custom next-generation sequencing (NGS) Ion AmpliSeq™ HD panels including 60 and 81 amplicons in 18 genes, respectively. Concordance of matching cancer-associated mutations in tissue and plasma was 73.3%. Mutant allele frequency (MAF) levels showed a range from 0.04% to 28.7%, well detectable with NGS technologies utilizing single molecule tagging like the AmpliSeq™ HD workflow. Median followup time of the tissue and/or plasma positive cohort (n = 15) was 24.6 months and median progression-free survival (PFS) was 7.8 months. Higher MAF ≥ 1% at baseline was not significantly associated with a risk of progression (Odds Ratio = 0.15; p = 0.155). Although a trend could be seen, MAF levels did not differ significantly over time between patients with and without a PFS event (p = 0.745). Depending on the cell-free DNA amount, NGS achieved a sensitivity down to 0.1% MAF and allowed for parallel analysis of multiple mutations and previously unknown mutations. Our study indicates that NGS gene panels could be useful for monitoring disease burden during therapy with ctDNA in melanoma patients.

Cell-free DNA analysis reveals POLR1D-mediated resistance to bevacizumab in colorectal cancer.

BACKGROUND: Bevacizumab, a monoclonal antibody against soluble VEGFA, is an approved and commonly administered anti-angiogenic drug in patients with metastasized colorectal cancer (mCRC). The survival benefit of anti-VEGF therapy in mCRC patients is limited to a few months, and acquired resistance mechanisms are largely unknown. Here, we employed whole-genome sequencing of plasma DNA to evaluate the tumor genome of patients undergoing treatment with bevacizumab to determine novel aberrations associated with resistance. METHODS: Using longitudinal plasma analyses, we studied the evolution of tumor genomes in a mCRC cohort (n = 150) and conducted analyses of CRC cases from The Cancer Genome Atlas (TCGA) database (n = 619) to identify associations between genomic aberrations and clinical features. We employed whole-genome sequencing to identify the most frequently occurring focal somatic copy number alterations (SCNAs). Using the TCGA data as a comparative and supporting dataset, we defined the minimally amplified overlapping region and studied the mechanistic consequences of copy number gain of the involved genes in this segment. In addition, we established an in vitro cell model and conducted downstream gene expression and cell viability assays to confirm our findings from the patient dataset. RESULTS: We observed a recurrent focal amplification (8.7% of cases) on chromosome 13q12.2. Analysis of CRC cases from the TCGA database suggested that this amplicon is associated with more advanced stages. We confirmed that this 13q12.2 amplicon frequently emerges later during the clinical course of disease. After defining the minimally amplified region, we observed that the amplification and expression of one gene, POLR1D, impacted cell proliferation and resulted in upregulation of VEGFA, an important regulator of angiogenesis which has been implicated in the resistance to bevacizumab treatment. In fact, in several patients, we observed the emergence of this 13q12.2 amplicon under bevacizumab treatment, which was invariably associated with therapy resistance. CONCLUSIONS: Non-invasive analyses of cell-free DNA from patients undergoing treatment with bevacizumab enabled the tracking of evolving tumor genomes and helped identify a recurrent focal SCNA of clinical relevance. Here, we describe a novel resistance mechanism against a widely applied treatment in patients with mCRC which will impact the clinical management of patients.