LiMAx test and ultrasound elastography to measure biomarkers of declining liver function in patients with liver fibrosis: A correlation analysis.

BACKGROUND: Monitoring liver changes is crucial in the management of liver fibrosis. Current diagnostic methods include liver function tests such as the Liver Maximum Capacity (LiMAx) test and measurements of liver stiffness. While the LiMAx test quantifies liver function through 13C-methacetin metabolism, ultrasound (US) elastography noninvasively assesses liver stiffness. The relationship between the findings of these methods in patients with liver fibrosis is not fullyunderstood. OBJECTIVE: This study evaluated the correlation between LiMAx measurements of liver function and US elastography-based liver stiffness measurements to better understand the interplay between functional and structural liver parameters in fibrotic liver disease. Additionally, the relationship between body mass index (BMI) and these parameters isevaluated. METHODS: This retrospective study analysed data from 97 patients who underwent both LiMAx testing and real-time elastography, resulting in a total data set of 108 examinations. The correlations between the results of the LiMAx test and elastography and their relationships with body mass index (BMI) were analysed. RESULTS: There was a significant negative correlation (r = -0.25, p < 0.05) between LiMAx test values and liver stiffness measurements. BMI was significantly negatively correlated with LiMAx values (r = -0.29, p < 0.001) but not significantly correlated with liver stiffness values. CONCLUSIONS: This retrospective study confirms the results of previous studies showing a notable but weak association between liver function and liver stiffness. Our results highlight the potential value of both tests as complementary tools for the evaluation of liver health, reinforcing the necessity for a multimodal approach to liver assessment.

Differentiating Well-Differentiated from Poorly-Differentiated HCC: The Potential and the Limitation of Gd-EOB-DTPA in the Presence of Liver Cirrhosis.

This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease.

Progress of Ossification after Mandibular Reconstruction by Free Fibula Flap Depending on Different Timing of Radiotherapy: A Retrospective 3D Analysis by CT Scans.

Background: The aim of this study was to evaluate the difference between pre- and post-operative radiotherapy on the progress of ossification after free fibula flap reconstruction of the mandible using three-dimensional (3D) analysis. Methods: A total of 38 free fibula reconstructions of the mandible were evaluated retrospectively for ossification between bone segments by measuring Hounsfield Units (HU) in at least two postoperative computer tomography scans (average of 2.4 scans per patient; around the 5th, 12th, 16th, and 19th month postoperative). Three subgroups were created according to the time of irradiation: preoperative radiotherapy (preORT) (n = 11), postoperative radiotherapy (postORT) (n = 16), and patients without any radiation therapy (n = 11) as the control group (noRT). HU in eight regions of interest (ROI) and overlapping surfaces between segments per contact point, as well as influencing factors, were analyzed. Results: The fastest progress in gain of HU ossification with a difference of 0.30 HU/day was observed in noRT compared to preORT (p = 0.002). postORT was -0.24 HU/day slower than preORT (p = 0.005). Original and grafted bone showed a significantly slower HU uptake than between two graft segments with -84.18 HU/day (p < 0.001). Moreover, a larger initial overlapping surface between the segments in cm2 resulted in a higher rise of HU/day (p < 0.001). Conclusions: 3D analysis of post-reconstructive CT scans shows prolonged ossification of mandible reconstructions by free fibula after head and neck radiation. The effect is distinct in cases with post-operative adjuvant radiotherapy. The effects of radiotherapy on ossification may be minimized by a larger initial contact surface and improved operational techniques. Moreover, HU longitudinal measurements and 3D analysis offer new perspectives for clinical evaluation of successful bony healing.

Peri-interventional LiMAx test for liver ablation - A feasibility study.

BACKGROUND: Local ablation is an important treatment for liver cancer in cases of cirrhosis. Liver failure may occur after ablation, especially in advanced liver diseases. Currently, there is no standardization for peri-interventional risk assessment. The liver maximum capacity test (LiMAx) is used to assess functional liver capacity, but there is a lack of exploration of its use in this context. OBJECTIVE: The aim of this study was to retrospectively evaluate the usefulness of peri-interventional LiMAx measurements in patients with primary or secondary liver cancer who underwent ablation treatment. METHODS: A LiMAx test was performed at 24 hours pre- and postablation in 49 patients. Blood parameters were collected to determine liver function using MELD and ALBI scores. The results of the LiMAx test were related with these scores and to critical postintervention LiMAx values. RESULTS: LiMAx values correlated strongly with MELD and ALBI scores before the intervention and reflected the change in liver function, as shown by an increase in scores after the intervention. Notably, LiMAx values decreased during the intervention. AUC analysis for patients at risk of reaching a critical liver level after the intervention showed a cutoff value of 186µg/kg/h. CONCLUSIONS: The LiMAx test may be a valuable tool in liver ablation for both peri-interventional monitoring of liver function and preintervention risk assessment.

Diagnostic Value of Diffusion-Weighted Imaging with Background Body Signal Suppression (DWIBS) for the Pre-Therapeutic Loco-Regional Staging of Cervical Cancer: A Feasibility and Interobserver Reliability Study.

(1) Background: cervical cancer is one of the leading causes of cancer-related deaths and the fourth most common cancer among women worldwide. Magnetic resonance imaging (MRI) is the modality of choice for loco-regional staging of cervical cancer in the primary diagnostic workup beginning with at least stage IB. (2) Methods: we retrospectively analyzed 16 patients with histopathological proven cervical cancer (FIGO IB1−IVA) for the diagnostic accuracy of standard MRI and standard MRI with diffusion-weighted imaging with background body signal suppression (DWIBS) for the correct pre-therapeutic assessment of the definite FIGO category. (3) Results: In 7 out of 32 readings (22%), DWIBS improved diagnostic accuracy. With DWIBS, four (13%) additional readings were assigned the correct major (I−IV) FIGO stages pre-therapeutically. Interobserver reliability of DWIBS was weakest for parametrial infiltration (k = 0.43; CI-95% 0.00−1.00) and perfect for tumor size <2 cm, infiltration of the vaginal lower third, infiltration of adjacent organs and loco-regional nodal metastases (k = 1.000; CI-95% 1.00−1.00). (4) Conclusions: the pre-therapeutic staging of cervical cancer has a high diagnostic accuracy and interobserver reliability when using standard MRI but can be further optimized with the addition of DWIBS sequences when reporting is performed by an experienced radiologist.

Case Report: Extramedullary Acute Promyelocytic Leukemia: An Unusual Case and Mini-Review of the Literature.

Background: Acute promyelocytic leukemia (APL) constitutes a serious hematological emergency necessitating rapid diagnosis and therapy to prevent lethal bleedings resulting from APL-induced thrombocytopenia and coagulopathy. Atypical manifestations of APL, such as extramedullary disease at first presentation, pose diagnostic challenges and delay the onset of appropriate therapy. Nevertheless, extramedullary manifestations of APL are mostly accompanied by blood count alterations pointing to an underlying hematological disease. In this report, we present the first case of APL bearing close resemblance to a metastasized laryngeal carcinoma with normal blood counts and absent coagulopathy. Case Presentation: A 67-year-old man with a previous history of smoking was admitted to our hospital with progressive hoarseness of voice, odynophagia, dysphagia and exertional dyspnea. Laryngoscopy revealed a fixed right hemi larynx with an immobile right vocal fold. Imaging of the neck via magnetic-resonance imaging (MRI) and positron emission tomography-computed tomography (PET/CT) with F-18-fluordeoxyglucose (FDG) showed a large hypermetabolic tumor in the right piriform sinus and tracer uptake in adjacent lymph nodes, highly suspicious of metastasized laryngeal carcinoma. Surprisingly the histological examination revealed an extramedullary manifestation of acute promyelocytic leukemia. Remarkably, blood counts and coagulation parameters were normal. Moreover, no clinical signs of hemorrhage were found. PML-RARA fusion was detected in both laryngeal mass and bone marrow. After diagnosis of APL, ATRA-based chemotherapy was initiated resulting in complete remission of all APL manifestations. Conclusions: This is the first case report of APL initially presenting as laryngeal chloroma. Additionally, we performed a comprehensive literature review of previously published extramedullary APL manifestations. In aggregate, a normal blood count at first presentation constitutes an extremely rare finding in patients initially presenting with extramedullary APL manifestations.

Update on Percutaneous Local Ablative Procedures for the Treatment of Hepatocellular Carcinoma. / Aktueller Stand zu perkutanen lokalablativen Verfahren beim hepatozellulären Karzinom.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide. Because many hepatocellular carcinomas are already unresectable at the time of initial diagnosis, percutaneous tumor ablation has become established in recent decades as a curative therapeutic approach for very early (BCLC 0) and early (BCLC A) HCC. The aim of this paper is to provide a concise overview of the percutaneous local ablative procedures currently in use, based on their technical characteristics as well as clinical relevance, taking into account the current body of studies. MATERIALS AND METHODS: The literature search included all original papers, reviews, and meta-analyses available via MEDLINE and Pubmed on the respective percutaneous ablation procedures; the primary focus was on randomized controlled trials and publications from the last 10 years. RESULTS AND CONCLUSIONS: Radiofrequency ablation (RFA) and microwave ablation (MWA) are well-established procedures that are considered equal to surgical resection in the treatment of stage BCLC 0 and A HCC with a diameter up to 3 cm due to their strong evidence in international and national guidelines. For tumors with a diameter between 3 and 5 cm, the current S3 guidelines recommend a combination of transarterial chemoembolization (TACE) and thermal ablation using RFA or MWA as combination therapy is superior to thermal ablation alone in tumors of this size and shows comparable results to surgical resection in terms of overall survival. Alternative, less frequently employed thermal procedures include cryotherapy (CT) and laser ablation (LA). Non-thermal procedures include irreversible electroporation (IRE), interstitial brachytherapy (IBT), and most recently, electrochemotherapy (ECT). Due to insufficient evidence, these have only been used in individual cases and within the framework of studies. However, the nonthermal methods are a reasonable alternative for ablation of tumors adjacent to large blood vessels and bile ducts because they cause significantly less damage to these structures than thermal ablation methods. With advances in the technology of the respective procedures, increasingly good evidence, and advancements in supportive techniques such as navigation devices and fusion imaging, percutaneous ablation procedures may expand their indications for the treatment of larger and more advanced tumors in the coming years. KEY POINTS: · RFA and MWA are considered equal to surgical resection as a first-line therapy for the curative treatment of stage BCLC 0 and A HCCs with a diameter of up to 3 cm.. · For HCCs with a diameter between 3 and 5 cm, a combination of TACE and RFA or MWA is recommended. This combination therapy yields results comparable to those of surgical resection in terms of overall survival.. · Due to insufficient evidence, alternative ablation methods have only been used in individual cases and within the framework of studies. However, nonthermal methods, such as IRE, IBT, and, most recently, ECT, are a reasonable alternative for ablation of HCCs adjacent to large blood vessels and bile ducts because they cause significantly less damage to these structures than thermal ablation methods.. CITATION FORMAT: · Luerken L, Haimerl M, Doppler M et al. Update on Percutaneous Local Ablative Procedures for the Treatment of Hepatocellular Carcinoma. Fortschr Röntgenstr 2022; 194: 1075 - 1086.

Stereotactic Microwave Ablation of Hepatocellular Carcinoma: The Impact of Tumor Size and Minimal Ablative Margin on Therapeutic Success.

BACKGROUND: Microwave ablation (MWA) has gained relevance in the treatment of hepatic malignancies and especially in hepatocellular carcinoma (HCC), and it is an important alternative to surgery. The purpose of the study was to evaluate whether the minimal ablative margin (MAM) or the initial tumor size has a greater effect on the success of stereotactic MWA of HCC regarding the time to local tumor progression (LTP) and overall survival (OS). METHODS: 88 patients, who received stereotactic MWA of 127 tumor lesions with a curative intention were included in this single-center, retrospective study. The MAM was evaluated in a side-by-side comparison of pre- and post-ablative, contrast-enhanced slice imaging. A Cox proportional hazard model with a frailty term was computed to assess the influence of the MAM and the maximum tumor diameter on the time to LTP and the OS. RESULTS: The maximum tumor diameter was identified as a significant positive predictor for LTP (hazard ratio 1.04, 95% CI 1.00-1.08, p = 0.03), but it was not a significant positive predictor for the OS (p = 0.20). The MAM did not have a significant influence on LTP-free survival (p = 0.23) and OS (p = 0.67). CONCLUSION: For the successful stereotactic MWA of HCC, the MAM and maximum tumor diameter might not have an influence on the OS, but the maximum tumor diameter seems to be an independent predictor of the time to LTP.

Complementary imaging of ultrasound and PET/CT: A new opportunity?

AIM: To evaluate the effectiveness of complementary imaging of high-resolution ultrasound including CEUS with PET/CT for tissue characterization and tumor detection. MATERIAL AND METHODS: 100 patients were examined with PET/CT and US/CEUS between January 2018 until February 2020. All patients underwent PET/CT followed by selective US/CEUS within 4 weeks. Comparison regarding concordant or diverging findings in PET/CT and US. Analysis of the differences concerning the lesions number of found by PET/CT and US/CEUS or the possibility of a secured diagnosis following ultrasound causing therapeutic changes. RESULTS: Diverging findings regarding the number of liver lesions in PET/CT and CEUS were found in 35 out of 64 patients (54%). Regarding renal lesions, a more definite diagnosis following ultrasound, causing a change of therapeutic approach, was achieved in 89%. Concordant results in PET/CT and US were found in 83% of patients with splenic and nodal findings. In 78% of patients with increased musculoskeletal or soft tissue tracer uptake, US was able to make a secured diagnosis with therapeutic changes. CONCLUSION: The present results indicate a strong benefit of complementary imaging of PET/CT and selective, high-resolution ultrasound especially in patients with liver, renal and musculoskeletal or soft tissue findings.

Diagnostic performance of quantitative and qualitative parameters for the diagnosis of aortic graft infection using [18F]-FDG PET/CT.

PURPOSE: The aim of this study was the evaluation of quantitative and qualitative parameters for the diagnosis of aortic graft infection (AGI) using [18F]-FDG PET/CT. METHODS: PET/CT was performed in 50 patients with clinically suspected AGI. 12 oncological patients with aortic repair but without suspicion of AGI were included in the analysis to serve as control cohort. The [18F]-FDG uptake pattern around the graft was assessed using (a) a five-point visual grading scale (VGS), (b) SUVmax and (c) different graft-to-background ratios (GBRs). The diagnostic performance of VGS, SUVmax and GBRs was assessed and compared by ROC analysis. RESULTS: 28 infected and 34 uninfected grafts were identified by standard of reference. SUVmax and VGS were the most powerful predictors for the diagnosis of AGI according to the area under the curve (AUC 0.988 and 0.983, respectively) without a significant difference compared to GBRs. SUVmax and VGS showed congruent and accurate findings in 54 patients (i.e. either both positive or negative), yielding sensitivity and specificity (100%) in this subgroup of patients. CONCLUSION: Quantitative analysis by SUVmax and qualitative analysis by VGS are highly effective in the diagnosis of AGI and should be tested as an outcome measure in prospective trials.

Primary efficacy of percutaneous microwave ablation of malignant liver tumors: comparison of stereotactic and conventional manual guidance.

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.

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.

Improvement of the primary efficacy of microwave ablation of malignant liver tumors by using a robotic navigation system.

Background The aim of the study was to assess the primary efficacy of robot-assisted microwave ablation and compare it to manually guided microwave ablation for percutaneous ablation of liver malignancies. Patients and methods We performed a retrospective single center evaluation of microwave ablations of 368 liver tumors in 192 patients (36 female, 156 male, mean age 63 years). One hundred and nineteen ablations were performed between 08/2011 and 03/2014 with manual guidance, whereas 249 ablations were performed between 04/2014 and 11/2018 using robotic guidance. A 6-week follow-up (ultrasound, computed tomography and magnetic resonance imaging) was performed on all patients. Results The primary technique efficacy outcome of the group treated by robotic guidance was significantly higher than that of the manually guided group (88% vs. 76%; p = 0.013). Multiple logistic regression analysis indicated that a small tumor size (≤ 3 cm) and robotic guidance were significant favorable prognostic factors for complete ablation. Conclusions In addition to a small tumor size, robotic navigation was a major positive prognostic factor for primary technique efficacy.

18F-FDG PET/MRI compared with clinical and serological markers for monitoring disease activity in patients with aortitis and chronic periaortitis.

OBJECTIVES: We compared the diagnostic value of fully integrated 18F-FDG PET/MRI to that of clinical and serological markers for monitoring disease activity in patients with aortitis/chronic periaortitis (A/CPA) during immunosuppressive therapy. METHODS: Patients positive for A/CPA at the initial and at least 2 consecutive PET/MRI studies were included for retrospective analysis. Imaging (qualitative and quantitative analysis), clinical, and serologic (C-reactive protein, erythrocyte sedimentation rate) assessments were determined at each visit, and their findings compared. Differences in various PET/MRI parameters, clinical symptoms, and serologic markers during therapy between first and second visits were tested for statistical significance. Spearman's rank correlation coefficient was calculated to relate imaging to serologic marker changes between the first 2 visits. RESULTS: Serial assessments were performed in 12 patients with A/CPA, over 34 visits. PET/MRI suggested active disease in 22/34 (64.7%) studies, whereas clinical assessment and serological analysis were positive in only 18/34 (52.9%) and 17/34 (50%) cases, respectively. Disease activity assessment differed between PET/MRI, and clinical and serological markers, in 8/34 (23.5%) and 9/34 (26.5%) cases, respectively. Imaging and serologic parameters (p < 0.009) and clinical symptoms (p = 0.063) predominantly improved at the second visit. Changes from the first to the second visit were not correlated between PET/MRI and serologic markers. CONCLUSIONS: Fully integrated 18F-FDG PET/MRI provides a comprehensive imaging approach with data on vascular/perivascular inflammation that is complementary to clinical and laboratory assessments. This highlights the potential value of imaging-based disease activity monitoring, which might have a crucial impact on clinical management in patients with A/CPA.

Full-Core Biopsy Systems Take Larger Liver Tissue Samples with Lower Fragmentation Rates Than Conventional Side-Notch Systems: A Randomized Trial.

BACKGROUND: The aim of this study was to compare the histopathological quality and physical features of the specimen of a full-core end-cut biopsy system with that of the standard side-notch system for liver biopsies. METHODS: A full-core end-cut 16G biopsy device and a standard side-notch 16G needle were used to take biopsies of unclear liver lesions. Patients were randomized in two groups of 16 patients each. The primary endpoint of this prospective study was the core length measured using a dedicated microscope imaging software. Secondary endpoints were the quality of the specimen rated by an independent pathologist unaware of the device (scale from 1 to 5; with 1 as best and 5 as worst), the core diameter (determined by the microscopic imaging software) and presence of fragmentation (evaluated by the pathologist). RESULTS: For the full-core (FC) and side-notch (SN) groups, the mean core length was similar with 13,599 µm and 11,570 µm (p=0.131), respectively. The quality of the specimen was significantly better in the FC-group with an average rating of 1.68 vs 2.50 (p=0.009). The fragmentation rate in the FC-group was statistically significantly lower at 2/27 (7%) than in the SN-group at 13/33 (39%) (p=0.021). The diameter in the FC-group was 1042 µm vs 930 µm in SN-group (p=0.018).

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 post-ablation 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.

Vertebral bone marrow fat fraction changes in postmenopausal women with breast cancer receiving combined aromatase inhibitor and bisphosphonate therapy.

BACKGROUND: Quantification of vertebral bone marrow (VBM) water-fat composition has been proposed as advanced imaging biomarker for osteoporosis. Estrogen deficiency is the primary reason for trabecular bone loss in postmenopausal women. By reducing estrogen levels aromatase inhibitors (AI) as part of breast cancer therapy promote bone loss. Bisphosphonates (BP) are recommended to counteract this adverse drug effect. The purpose of our study was to quantify VBM proton density fat fraction (PDFF) changes at the lumbar spine using chemical shift encoding-based water-fat MRI (CSE-MRI) and bone mineral density (BMD) changes using dual energy X-ray absorptiometry (DXA) related to AI and BP treatment over a 12-month period. METHODS: Twenty seven postmenopausal breast cancer patients receiving AI therapy were recruited for this study. 22 subjects completed the 12-month study. 14 subjects received AI and BP (AI+BP), 8 subjects received AI without BP (AI-BP). All subjects underwent 3 T MRI. An eight-echo 3D spoiled gradient-echo sequence was used for CSE-based water-fat separation at the lumbar spine to generate PDFF maps. After manual segmentation of the vertebral bodies L1-L5 PDFF values were extracted for each vertebra and averaged for each subject. All subjects underwent DXA of the lumbar spine measuring the average BMD of L1-L4. RESULTS: Baseline age, PDFF and BMD showed no significant difference between the two groups (p > 0.05). There was a relative longitudinal increase in mean PDFF (∆relPDFF) in both groups (AI+BP: 5.93%; AI-BP: 3.11%) which was only significant (p = 0.006) in the AI+BP group. ∆relPDFF showed no significant difference between the two groups (p > 0.05). There was no significant longitudinal change in BMD (p > 0.05). CONCLUSIONS: Over a 12-month period, VBM PDFF assessed with CSE-MRI significantly increased in subjects receiving AI and BP. The present results contradict previous results regarding the effect of only BP therapy on bone marrow fat content quantified by magnetic resonance spectroscopy and bone biopsies. Future longer-term follow-up studies are needed to further characterize the effects of combined AI and BP therapy.

In vivo confirmation of altered hepatic glucose metabolism in patients with liver fibrosis/cirrhosis by 18F-FDG PET/CT.

OBJECTIVE: The aim of this study was to assess the value of 18F-FDG PET/CT for quantitative assessment of hepatic metabolism in patients with different stages of liver fibrosis/cirrhosis. MATERIALS AND METHODS: 18F-FDG PET/CT scans of 37 patients either with or without liver fibrosis/cirrhosis, classified according to the METAVIR score (F0-F4) obtained from histopathological analysis of liver specimen, were analyzed retrospectively and classified as follows: no liver fibrosis (F0, n = 6), mild liver fibrosis (F1, n = 11), advanced liver fibrosis (F2, n = 6), severe liver fibrosis (F3, n = 5), and liver cirrhosis (F4, n = 11). The liver-to-blood ratio (LBR, scan time corrected for a reference time of 75 min) was compared between patient groups. RESULTS: Patients with liver fibrosis or cirrhosis (≥ F1; LBR 1.53 ± 0.35) showed a significant higher LBR than patients with normal liver parenchyma (F0, 1.08 ± 0.23; P = 0.004). In direct comparison, LBR increased up to the advanced stage of liver fibrosis (F2; 2.00 ± 0.40) and decreased until liver cirrhosis is reached (F4, 1.32 ± 0.14). CONCLUSION: Functional changes in liver parenchyma during liver fibrosis/cirrhosis affect hepatic glucose metabolism and significantly differ between stages of liver fibrosis/cirrhosis, classified according to the METAVIR scoring system, as demonstrated by LBR quantification by 18F-FDG PET/CT.

Improved detection rates and treatment planning of head and neck cancer using dual-layer spectral CT.

PURPOSE: The aim of this study was to evaluate the advantages of dual-layer spectral CT (DLSCT) in detection and staging of head and neck cancer (HNC) as well as the imaging of tumour margins and infiltration depth compared to conventional contrast enhanced CT (CECT). MATERIALS AND METHODS: Thirty-nine patients with a proven diagnosis of HNC were examined with a DLSCT scanner and retrospectively analysed. An age-matched healthy control group of the same size was used. Images were acquired in the venous phase. Virtual monoenergetic 40keV-equivalent (MonoE40) images were compared to CECT-images. Diagnostic confidence for tumour identification and margin detection was rated independently by four experienced observers. The steepness of the Hounsfield unit (HU)-increase at the tumour margin was analysed. External carotid artery branch image reconstructions were performed and their contrast compared to conventional arterial phase imaging. Means were compared using a Student's t-test. ANOVA was used for multiple comparisons. RESULTS: MonoE40 images were superior to CECT-images in tumour detection and margin delineation. MonoE40 showed significantly higher attenuation differences between tumour and healthy tissue compared to CECT-images (p < 0.001). The HU-increase at the boundary of the tumour was significantly steeper in MonoE40 images compared to CECT-images (p < 0.001). Iodine uptake in the tumour was significantly higher compared to healthy tissue (p < 0.001). MonoE40 compared to conventional images allowed visualisation of external carotid artery branches from the venous phase in a higher number of cases (87% vs. 67%). CONCLUSION: DLSCT enables improved detection of primary and recurrent head and neck cancer and quantification of tumour iodine uptake. Improved contrast of MonoE40 compared to conventional reconstructions enables higher diagnostic confidence concerning tumour margin detection and vessel identification. KEY POINTS: • Sensitivity concerning tumour detection are higher using dual-layer spectral-CT than conventional CT. • Lesion to background contrast in DLSCT is significantly higher than in CECT. • DLSCT provides sufficient contrast for evaluation of external carotid artery branches.

Ewing sarcoma partial regression without GvHD by chondromodulin-I/HLA-A*02:01-specific allorestricted T cell receptor transgenic T cells.

Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1-specific allorestricted T cell receptor (TCR) wild-type and transgenic cytotoxic (CD8+) T cells against ES. Patients and Methods: Three refractory HLA-A2+ ES patients were treated with HLA-A*02:01/peptide-specific allorepertoire-derived (i.e., allorestricted) CD8+ T cells. Patient #1 received up to 4.8 × 105/kg body weight HLA-A*02:01- allorestricted donor-derived wild-type CD8+ T cells. Patient #2 received up to 8.2 × 106/kg HLA-A*02:01- donor-derived and patient #3 up to 6 × 106/kg autologous allorestricted TCR transgenic CD8+ T cells. All patients were treated with the same TCR complementary determining region 3 allorecognition sequence for CHM1 peptide 319 (CHM1319). Results: HLA-A*02:01/CHM1319-specific allorestricted CD8+ T cells showed specific in vitro lysis of all patient-derived ES cell lines. Therapy was well tolerated and did not cause graft versus host disease (GvHD). Patients #1 and #3 showed slow progression, whereas patient #2, while having BM involvement, showed partial metastatic regression associated with T cell homing to involved lesions. CHM1319 TCR transgenic T cells could be tracked in his BM for weeks. Conclusions: CHM1319-TCR transgenic T cells home to affected BM and may cause partial disease regression. HLA-A*02:01/antigen-specific allorestricted T cells proliferate in vivo without causing GvHD.