Changes in Posttreatment Spleen Volume Associated with Immunotherapy Outcomes for Advanced Hepatocellular Carcinoma.

Purpose: We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib. Patients and Methods: Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation. Tumor assessment followed Response Evaluation Criteria in Solid Tumors version 1.1. The association between SV change and tumor response or progression-free survival (PFS) was analyzed. The inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics. Results: The immunotherapy group comprised 143 patients (124 men, mean age, 59.8 years ± 11.2 [standard deviation]), while the sorafenib group had 57 (47 men, mean age, 59.6 years ± 9.9). SV increased in 108 (75.5%) immunotherapy and 21 (36.8%) sorafenib patients. In the immunotherapy group, patients with increased SV were more likely than those with decreased SV to have a higher disease control rate (76.9% vs 57.1%, p = 0.024) and durable clinical benefit (52.8% vs 25.7%, p = 0.005). It was also associated with extended PFS in the immunotherapy group in both the univariate (p = 0.028) and multivariate (p = 0.014) analysis. By contrast, in the sorafenib group, an increased in SV was not associated with treatment response but was presumably associated with reduced PFS (p = 0.072) in the multivariate analysis. After IPTW adjustment, the increase in SV remained a significant predictor for DCB and PFS in the immunotherapy group. Conclusion: Most patients exhibited an increase in SV after the initiation of immunotherapy, which may be used to predict response and prognosis. However, this association was not observed in patients who received sorafenib.

The study provides significant evidence that an increase in spleen volume is associated with better treatment outcomes in advanced hepatocellular carcinoma patients undergoing immunotherapy. These findings offer oncologists a new potential biomarker for optimizing treatment strategies. Specifically, increased spleen volume could be used to predict higher rates of disease control and durable clinical benefits, allowing for more personalized care.

PET/MRI in Endometrial Cancer: Imaging Biomarkers are Associated with Disease Progression and Overall Survival.

RATIONALE AND OBJECTIVES: To evaluate the association between positron emission tomography (PET)/magnetic resonance imaging (MRI) biomarkers and survival outcomes in patients with endometrial cancer. MATERIALS AND METHODS: Between April 2014 and April 2016, 88 patients with newly diagnosed endometrial cancer participated this prospective study and underwent [18F] fluorodeoxyglucose PET/MRI. Sixty-nine patients with measurable tumors on PET/MRI were included in the image analysis. Imaging biomarkers included the minimum and mean apparent diffusion coefficients (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. The log-rank test and Cox proportional hazards model were used to assess the relationship between imaging biomarkers and survival. RESULTS: After a median follow-up of 80 months, 15 (22%) patients had tumor progression and six (9%) patients died. The results of ADCmin, ADCmean, and SUVmax did not show a significant association with progression-free survival (PFS) and overall survival (OS). Significantly shorter PFS was noted in patients with primary tumors with higher MTV (P < 0.001) and TLG (P < 0.001). Significantly shorter OS was also noted in patients with primary tumors with higher MTV (P = 0.048) and TLG (P = 0.034). In the multivariate analysis, MTV was an independent predictor of PFS (hazard ratio = 10.84, P = 0.033). CONCLUSION: PET/MRI biomarkers, particularly MTV and TLG, are associated with PFS and OS in patients with endometrial cancer. MTV was an independent predictor of PFS.

Ultrasound characteristics of soft tissues near sacroiliac joints and in the lumbar region of patients with ankylosing spondylitis.

AIMS: To investigate the musculoskeletal morphomechanical properties (i.e., the thickness and elastic modulus) and the total count of power Doppler signals near the sacroiliac joints in patients with ankylosing spondylitis (AS) and non-AS individuals. MATERIAL AND METHODS: Twenty participants with AS [median age (interquartile range): 31.7 (11.04) years] and 19 controls [36.3 (10.5) years] with no AS history were recruited. Bilateral ultrasound image acquisition was performed, including the short posterior sacroiliac ligament, interosseous sacroiliac ligament, long posterior sacroiliac ligament, iliolumbar ligament, proximal piriformis muscle, and sacrotuberous ligament. The intraclass correlation coefficients (ICC) of ultrasound parameters, laboratory test results of human leukocyte antigen B27, C-reactive protein, and erythrocyte sedimentation rate, and self-reported physical and disease activity scores were also obtained. RESULTS: The ligaments and piriformis muscle were thicker and stiffer (greater elastic modulus) in participants with AS than in non-AS participants (all p<0.01). The measurements showed good or excellent reliability (all ICC(3,1) >0.85). The numbers of power Doppler signals detected in the iliolumbar ligament, proximal piriformis muscle, and sacrotuberous ligament were higher in participants with AS than in non-AS participants (all p<0.001). A correlation was identified between disease duration and the elastic modulus of the piriformis muscle (r=0.640, p=0.003). CONCLUSION: We conclude that the ligaments and proximal piriformis muscle of AS participants have increased thickness, elastic modulus, and power Doppler signal than those of non-AS individuals. These reliable findings may serve as potential markers for the early diagnosis of AS and for assessing medication effects.

Kinematic magnetic resonance imaging for the evaluation of active motion of the mandibular condyle in patients with temporomandibular joint disorders.

PURPOSE: To explore the mandibular condylar movements in patients with temporomandibular joint (TMJ) disorders using kinematic magnetic resonance imaging (MRI). METHODS: We retrospectively recruited patients who were clinically diagnosed with internal derangement of the TMJ and referred to our center for MRI examination. The TMJ discs were categorized into normal disc (ND), anteriorly displaced disc (ADD), and disc with destruction (DD) groups using static images obtained in the closed-mouth view. The difference between the "open-mouth" and "closed-mouth" views on kinematic MRI was used to calculate the condylar translation and rotation. Two radiologists consensually performed the image readings and measurements. One-way analysis of variance and chi-squared test were used to compare the variables in the three groups. Pearson's correlation and general linear models were used to evaluate the correlation and differences between condylar translation and rotation in the three groups. RESULTS: This study included 98 TMJs from 54 patients. Twenty-six, 49, and 23 TMJs were classified as ND, ADD, and DD, respectively. Condylar rotation and translation demonstrated a significant correlation in all TMJs examined (r = 0.635, p < 0.001), with similar coefficients for all groups. The mean condylar translation in the ND group was greater than that in the ADD and DD groups (ND versus ADD: p = 0.003; ND versus DD: p = 0.002). However, the change in condylar rotation was not affected by the disc status (ND as reference; DD∗condylar translation: coefficient = 0.341, p = 0.332; ADD∗condylar translation: coefficient = -0.100, p = 0.696). CONCLUSION: Kinematic MRI studies revealed that TMJ condylar translation was correlated with its rotation for all disc statuses.

Sarcopenia and myosteatosis are associated with survival in patients receiving immunotherapy for advanced hepatocellular carcinoma.

OBJECTIVES: To investigate the association of sarcopenia, myosteatosis, and sarcopenic obesity with survival outcomes among patients who underwent immunotherapy for advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective analysis, patients who initiated immunotherapy for advanced HCC were enrolled. Sarcopenia and myosteatosis were evaluated on pretreatment CT at L3 level by skeletal muscle index and mean muscle attenuation using predefined cutoff values. Sarcopenic obesity was defined as concurrent sarcopenia and body mass index > 25 kg/m2. The log-rank test and the Cox proportional hazards model were used to compare overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 138 patients was included (discovery cohort n = 111, validation cohort n = 27). In the discovery cohort, patients with sarcopenia exhibited significantly poorer PFS (p = 0.048) and OS (p = 0.002) than patients without sarcopenia. Patients with myosteatosis exhibited significantly poorer PFS (p < 0.001) and OS (p < 0.001) than patients without myosteatosis. Patients with sarcopenic obesity compared to patients without sarcopenic obesity exhibited significantly poorer OS (p = 0.006) but not PFS (p = 0.31). In multivariate analysis adjusting for patient demographics, tumor extent, and liver function reserve, myosteatosis remained an independent predictor of poor PFS (p = 0.014) and OS (p = 0.007); sarcopenia remained an independent predictor for poor OS (p = 0.007). The prediction models for survival outcomes built by the discovery cohort showed similar performance in the validation cohort. CONCLUSIONS: Sarcopenia and myosteatosis are independent prognostic factors in patients who received immunotherapy for advanced HCC. KEY POINTS: • Sarcopenia and myosteatosis can be evaluated by CT at L3 level. • Sarcopenia, myosteatosis, and sarcopenic obesity were associated with poor survival outcomes in patients who underwent immunotherapy for advanced HCC. • Myosteatosis was an independent predictor of PFS and OS, and sarcopenia was independent for OS in these patients.

Muscle Microcirculatory Responses to Incremental Exercises Are Correlated with Peak Oxygen Uptake in Individuals With and Without Type 2 Diabetes Mellitus.

Background: The role of impaired oxygen extraction on peak oxygen uptake (V̇O2peak) has been extensively studied using noninvasive and indirect methods in both diabetic patients and healthy participants. Methods: A total of 22 participants with type 2 diabetes mellitus [T2DM; median (range) age: 60 (47-70) years] and 22 controls [58 (52-69) years] with no history of diabetes were recruited (reference no. 201812135RINB). Subjects performed an exhaustive incremental exercise and were evaluated using a gas analyzer and near-infrared spectroscopy (NIRS) to determine V̇O2peak and changes in muscle oxygenation (SmO2) in the vastus lateralis, respectively. Measurements were taken at rest, warm-up, a period during exercise when SmO2 reached a minimum saturation plateau, and recovery. The microcirculatory responses of the vastus lateralis muscle during incremental exercise in patients with T2DM were compared with those in control individuals, and the correlation between changes in SmO2 and V̇O2peak was estimated. Results: The diabetic group demonstrated lower V̇O2peak, peak workload, peak heart rate, peak minute ventilation (all P < 0.05), and lower SmO2 during the rest, warm-up, and recovery phases (all P < 0.05) compared with the control group. A correlation was observed between the change in SmO2 between the warm-up and plateau value and the V̇O2peak (r = 0.608, P = 0.006). Conclusions: The results obtained in this study using NIRS support the feasibility of directly measuring changes in muscle SmO2 magnitudes to estimate the contributions of peripheral active muscle to systemic O2 uptake (V̇O2) during incremental exercise.

Prediction of Mandibular Advancement Device Response Using CPAP Pressure in Different Polysomnographic Phenotypes.

Objective: Both continuous positive airway pressure (CPAP) pressure and polysomnographic phenotypes have been associated with mandibular advancement device (MAD) treatment response, but the precise relationship has not been fully elucidated. We hypothesized that utilizing CPAP pressure would predict the MAD response in treatment-naïve patients with moderate-severe obstructive sleep apnea (OSA), and the MAD response would be associated with two polysomnographic phenotypes, including sleep stage dependency and positional dependency. Methods: OSA treatment-naïve patients with an apnea-hypopnea index (AHI) ≥15/h who declined CPAP treatment and received MAD treatment for 3-6 months were enrolled. The MAD treatment response was defined as 1) residual AHI under MAD (AHIMAD) <5/h and 2) AHIMAD <10/h. Logistic regression was applied to identify the association between CPAP pressure and MAD treatment responders. The predictability of the MAD responder status utilizing CPAP pressure was assessed with the area under the receiver operating characteristic (AUROC). Results: A total of 128 enrolled patients (AHI ≥30/h in 74.2%) were recruited, of whom 119 patients and 80 patients were included for analysis of sleep stage and positional dependency, respectively. REM-predominant OSA had lower AHI than stage-independent OSA, while the supine-predominant phenotype had lower anthropometrics than the nonpositional-dependent phenotype. The response rates for AHIMAD <5/h and AHIMAD <10/h were 25.8% and 48.4%, respectively. Lower anthropometrics, baseline AHI, and supine predominance were associated with the responder status, while CPAP pressure was an independent predictor. The AUROCs for the prediction of AHIMAD <5/h and AHIMAD <10/h responders were 0.635 and 0.664, respectively. Utilizing a CPAP level >14 cmH2O as the cutoff to predict criterion 1 and 2 nonresponders, the sensitivity was 93.9% and 95.2%, respectively. Conclusion: In treatment-naïve patients with moderate-severe OSA, the supine-predominant phenotype and lower CPAP pressure were associated with the MAD response, while the sleep stage dependency phenotype was not. Utilization of a CPAP level >14 cmH2O could be a sensitive measure to identify nonresponders.

Predictors of changes in preoperative tumor stage between dynamic computed tomography and gadoxetate disodium-enhanced magnetic resonance imaging for hepatocellular carcinoma.

BACKGROUND/PURPOSE: Gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) has a higher diagnostic accuracy for hepatocellular carcinoma (HCC) than computed tomography (CT). However, indications for performing EOB-MRI after dynamic CT are not well defined. Therefore, we investigated the clinical factors associated with changes in the preoperative tumor stage between dynamic CT and EOB-MRI. METHODS: A prospective cohort was conducted from January 2014 to December 2017. 156 adult patients with clinical suspicion of HCC before liver resection were enrolled and we retrospectively reviewed the images. The tumor staging was evaluated by dynamic CT and then EOB-MRI subsequently according to the TNM staging system. The changes in tumor stage between two modalities were identified, and the associated clinical factors were analyzed. RESULTS: A total of 99 patients were analyzed after excluding 57 patients. 20 patients (20.2%) had changes in tumor stage between dynamic CT and EOB-MRI. The change occurred only in early stage (T1 and T2 lesions) based on dynamic CT initially. Furthermore, in univariate and multivariate analyses, albumin-bilirubin (ALBI) grade 2 and log alpha-fetoprotein (AFP) levels were associated with changes in tumor staging by EOB-MRI than those without (50% vs. 9.9%, p < 0.001 and 2.04 ± 1.35 vs. 1.40 ± 1.16, p = 0.038, respectively). Patients with changes in tumor stage also exhibited higher 1-year recurrence rate and shorter recurrence-free survival. CONCLUSION: Changes in preoperative tumor stage between dynamic CT and EOB-MRI were associated with CT-defined early stage, ALBI grades, higher log AFP levels, and early recurrence.

Early Changes in DCE-MRI Biomarkers May Predict Survival Outcomes in Patients with Advanced Hepatocellular Carcinoma after Sorafenib Failure: Two Prospective Phase II Trials.

In this paper, our main objective was to predict survival outcomes using DCE-MRI biomarkers in patients with advanced hepatocellular carcinoma (HCC) after progression from 1st-line sorafenib treatment in two prospective phase II trials. This study included 74 participants (men/women = 64/10, mean age 60 ± 11.8 years) with advanced HCC who received 2nd-line targeted therapy (n = 41 with lenalidomide in one clinical trial; n = 33 with axitinib in another clinical trial) after sorafenib failure from two prospective phase II studies. Among them, all patients underwent DCE-MRI at baseline, and on days 3 and 14 of treatment. The relative changes (Δ) in the DCE-MRI parameters, including ΔPeak, ΔAUC, and ΔKtrans, were derived from the largest hepatic tumor. The treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The Cox model was used to investigate the associations of the clinical variables and DCE-MRI biomarkers with progression-free survival (PFS) and overall survival (OS). The objective response rate (ORR) was 10.8% (8/74) and the disease control rate (DCR) was 58.1% (43/74). The median PFS and OS values were 1.9 and 7.8 months, respectively. On day 3 (D3), participants with high reductions in ΔPeak_D3 (hazard ratio (HR) 0.4, 95% confidence interval (CI) 0.17-0.93, p = 0.017) or ΔAUC_D3 (HR 0.51, 95% CI 0.25-1.04, p = 0.043) were associated with better PFS. On day 14, participants with high reductions in ΔPeak_D14 (HR 0.51, 95% CI 0.26-1.01, p = 0.032), ΔAUC_D14 (HR 0.54, 95% CI 0.33-0.9, p = 0.009), or ΔKtrans_D14 (HR 0.26, 95% CI 0.12-0.56, p < 0.001) had a higher PFS than those with lower reduction values. In addition, high reductions in ΔAUC_D14 (HR 0.53, 95% CI 0.32-0.9, p = 0.016) or ΔKtrans_D14 (HR 0.47, 95% CI 0.23-0.98, p = 0.038) were associated with a better OS. Among the clinical variables, ORR was associated with both PFS (p = 0.001) and OS (p = 0.005). DCR was associated with PFS (p = 0.002), but not OS (p = 0.089). Cox multivariable analysis revealed that ΔKtrans_D14 (p = 0.002) remained an independent predictor of PFS after controlling for ORR and DCR. An early reduction in tumor perfusion detected by DCE-MRI biomarkers, especially on day 14, may predict favorable survival outcomes in participants with HCC receiving 2nd-line targeted therapy after sorafenib failure.

Diagnostic Performance of Proton Magnetic Resonance Spectroscopy and 18F-Fluorocholine PET to Differentiate Benign From Malignant Breast Lesions.

PURPOSE: The aim of this study was to evaluate the diagnostic performance of the proton magnetic resonance spectroscopy (MRS) and 18F-fluorocholine (FCH) PET for suspicious breast findings on conventional imaging (mammography and breast ultrasound). METHODS: From September 2012 to December 2015, 37 women with 39 breast lesions on conventional imaging were enrolled and underwent proton MRS and FCH PET. The MRS parameters of choline signal-to-noise ratio (SNR), choline integral (I(cho)), and the PET parameters including SUVmax in the prone (SUV1) and supine (SUV2) positions were analyzed. Receiver operating characteristic curves with the area under the curve, sensitivity, and specificity under the optimal cutoff points for the different parameters were determined. RESULTS: Twenty-three lesions (59%) were malignant, and 16 (41.0%) were benign. The malignant lesions tended to show significantly higher MRS and PET parameters than benign lesions (choline SNR, P = 0.007; I(cho), P = 0.003; SUV1 and SUV2, P < 0.0001). Fair to moderate correlations were noted between the choline SNR and PET parameters (SUV1, Spearman rank correlation coefficient, ρ = 0.477; SUV2, ρ = 0.483), as well as I(cho) and PET parameters (SUV1, ρ = 0.493; SUV2, ρ = 0.549). The SUV2 showed the highest diagnostic performance (area under the curve, 0.918). Using 2.5 as the optimal cutoff point, the SUV2 yields 89.5% sensitivity and 87.5% specificity for differentiating malignant from benign lesions. CONCLUSION: The MRS parameters were fairly to moderately correlated with FCH PET parameters, and both could differentiate malignant from benign breast lesions with SUV2 showing best diagnostic performance.

Metabolic Alterations in Pancreatic Cancer Detected by In Vivo 1H-MR Spectroscopy: Correlation with Normal Pancreas, PET Metabolic Activity, Clinical Stages, and Survival Outcome.

OBJECTIVE: To compare the metabolites of in vivo 1H- MRS in pancreatic cancer with normal pancreas, and correlate these metabolites with Positron Emission Tomography (PET) metabolic activity, clinical stages, and survival outcomes. METHODS: The prospective study included 58 patients (mean age 62.7 ± 12.1 years, range 34-81 years; 36 men, 22 women) with pathological proof of pancreatic adenocarcinoma, and all of them received 18F-fluorodeoxyglucose (FDG) PET/MRI before treatment. The single-voxel MRS with a point-resolved selective spectroscopy sequence was used to measure metabolites (creatine, Glx (glutamine and glutamate), N-acetylaspartate (NAA), and lipid) of pancreatic cancer and adjacent normal parenchyma, respectively. FDG-PET parameters included SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Non-parametric tests were used to evaluate the differences of MRS metabolites between pancreatic cancer and those in normal pancreas, and their correlation with PET parameters and clinical stages. The correlation with progression-free survival (PFS) and overall survival (OS) was measured using the Kaplan-Meier and Cox proportional hazard models. RESULTS: When compared with normal pancreas, the Glx, NAA, and lipid levels were significantly decreased in pancreatic cancer (all p < 0.05). Creatine, Glx, and lipid levels were all inversely correlated with both MTV (rho = -0.405~-0.454) and TLG (rho = -0.331~-0.441). For correlation with clinical stages, lower lipid levels were found in patients with T4 (vs.

Safety and Efficacy of Kartigen® in Treating Cartilage Defects: A Randomized, Controlled, Phase I Trial.

Here, we aimed to investigate the safety and preliminary efficacy of Kartigen®, a matrix with autologous bone marrow mesenchymal stem cell-derived chondrocyte precursors embedded in atelocollagen. As a surgical graft, Kartigen® was implanted onto the cartilage defects at the weight-bearing site of the medial femoral condyle of the knee. Fifteen patients were enrolled and stratified into two groups, undergoing either Kartigen® implantation (n = 10) or microfracture (control group, n = 5). The primary endpoint was to evaluate the safety of Kartigen® by monitoring the occurrence of adverse events through physician queries, physical examinations, laboratory tests, and radiological analyses for 2 years. There were no infections, inflammations, adhesions, loose body, or tumor formations in the Kartigen®-implanted knees. The preliminary efficacy was assessed using the International Knee Documentation Committee (IKDC) score, visual analog scale, and second-look arthroscopy. The postoperative IKDC scores of the Kartigen® group significantly improved in the 16th week (IKDC = 62.1 ± 12.8, p = 0.025), kept increasing in the first year (IKDC = 78.2 ± 15.4, p < 0.005), and remained satisfactory in the second year (IKDC = 73.6 ± 13.8, p < 0.005), compared to the preoperative condition (IKDC = 47.1 ± 17.0), while the postoperative IKDC scores of the control group also achieved significant improvement in the 28th week (IKDC = 68.5 ± 6.1, p = 0.032) versus preoperative state (IKDC = 54.0 ± 9.1). However, the IKDC scores decreased in the first year (IKDC = 63.5 ± 11.6) as well as in the second year (IKDC = 52.6 ± 16.4). Thirteen patients underwent second-look arthroscopy and biopsy one year after the operation. The Kartigen® group exhibited integration between Kartigen® and host tissue with a smooth appearance at the recipient site, whereas the microfracture group showed fibrillated surfaces. The histological and immunohistochemical analyses of biopsy specimens demonstrated the columnar structure of articular cartilage and existence of collagen type II and glycosaminoglycan mimic hyaline cartilage. This study indicates that Kartigen® is safe and effective in treating cartilage defects.

Lumbar Disc Herniation Automatic Detection in Magnetic Resonance Imaging Based on Deep Learning.

Background: Lumbar disc herniation (LDH) is among the most common causes of lower back pain and sciatica. The causes of LDH have not been fully elucidated but most likely involve a complex combination of mechanical and biological processes. Magnetic resonance imaging (MRI) is a tool most frequently used for LDH because it can show abnormal soft tissue areas around the spine. Deep learning models may be trained to recognize images with high speed and accuracy to diagnose LDH. Although the deep learning model requires huge numbers of image datasets to train and establish the best model, this study processed enhanced medical image features for training the small-scale deep learning dataset. Methods: We propose automatic detection to assist the initial LDH exam for lower back pain. The subjects were between 20 and 65 years old with at least 6 months of work experience. The deep learning method employed the YOLOv3 model to train and detect small object changes such as LDH on MRI. The dataset images were processed and combined with labeling and annotation from the radiologist's diagnosis record. Results: Our method proves the possibility of using deep learning with a small-scale dataset with limited medical images. The highest mean average precision (mAP) was 92.4% at 550 images with data augmentation (550-aug), and the YOLOv3 LDH training was 100% with the best average precision at 550-aug among all datasets. This study used data augmentation to prevent under- or overfitting in an object detection model that was trained with the small-scale dataset. Conclusions: The data augmentation technique plays a crucial role in YOLOv3 training and detection results. This method displays a high possibility for rapid initial tests and auto-detection for a limited clinical dataset.

Iodized oil computed tomography versus ultrasound-guided radiofrequency ablation for early hepatocellular carcinoma.

BACKGROUND AND PURPOSE: Radiofrequency ablation (RFA) is the standard of care for early stage hepatocellular carcinoma (HCC). However, the clinical outcomes of iodized oil computed tomography (IoCT) versus ultrasound (US)-guided RFA for HCC remain unclear. METHODS: We retrospectively analyzed consecutive treatment-naïve patients who received curative RFA for HCC within Milan criteria from January 2016 to December 2018. Patients who underwent either IoCT-guided RFA (IoCT group) or US-guided RFA (US group) were included. Various clinical factors, including tumor location, were adjusted with a 1:1 propensity score matching. Subsequently, the cumulative incidence rates for recurrence and hazard ratios for survival were calculated. RESULTS: We included 184 (37.9%) and 301 (62.1%) patients who received IoCT- and US-guided RFA, respectively. Before propensity score matching, IoCT guidance was significantly associated with multiple tumors, higher body mass index, lower albumin level, and tumors located at S8. After matching, the 1-, 2-, and 3-year local tumor progression rates of the IoCT group were significantly lower than those of the US group (4.4%, 6.9%, and 7.5% vs. 14.4%, 16.3%, and 16.3%, respectively, at p = 0.002, 0.009, and 0.016, respectively). In univariate analyses and multivariate analyses that adjusted for clinical and tumor location-related parameters, the IoCT group had better recurrence-free survival (hazard ratio = 0.581, 95% confidence interval 0.375-0.899) than those with US guidance but not overall survival. CONCLUSION: IoCT-guided RFA had a lower local tumor progression rate and better recurrence-free survival than did US-guided RFA for HCC within the Milan criteria. CT-guide RFA is a safe and effective alternative to US-guided with similar overall survival. IoCT-guided RFA might have a better local tumor control than US-guided. IoCT-guided RFA may be more suitable for male patients, aged < 70 years, a single tumor measuring 2-5 cm, and a tumor located at the subdiaphragmatic/subcardiac region.

Dynamic Contrast-Enhanced and Intravoxel Incoherent Motion MRI Biomarkers Are Correlated to Survival Outcome in Advanced Hepatocellular Carcinoma.

OBJECTIVE: This study assessed dynamic contrast-enhanced (DCE)-MRI and intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) parameters to prospectively predict survival outcomes in participants with advanced hepatocellular carcinoma (HCC) who received lenalidomide, a dual antiangiogenic and immunomodulatory agent, as second-line therapy in a Phase II clinical trial. MATERIALS AND METHODS: Forty-four participants with advanced HCC who had progression after sorafenib as first-line treatment were prospectively enrolled. Pretreatment MRI parameters-obtained from DCE-MRI (peak, slope, AUC, Ktrans, Kep, and Ve), apparent diffusion coefficient (ADC), and IVIM DWI (pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f))-were derived from the largest hepatic tumor. The Cox model was used to investigate the associations of the parameters with progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS and OS were 2.3 and 8.0 months, respectively. Univariate analysis showed that participants with a high slope (p = 0.024), Kep (p < 0.001), and ADC (p = 0.018) values had longer PFS than those with low values; participants with a small tumor size (p = 0.006), high slope (p = 0.01), ADC (p = 0.015), and f (p = 0.012) values had longer OS than those with low values did. Cox multivariable analysis revealed that Kep (p < 0.001) and ADC (p = 0.009) remained independent predictors of PFS; slope (p = 0.003) and ADC (p = 0.009) remained independent predictors of OS. Moreover, Kep and slope were still significant after Bonferroni correction was performed (p < 0.005). CONCLUSION: Both pretreatment DCE-MRI and IVIM DWI parameters, especially slope and ADC, may predict PFS and OS in participants with HCC receiving lenalidomide as second-line therapy.

Atelocollagen-Embedded Chondrocyte Precursors as a Treatment for Grade-4 Cartilage Defects of the Femoral Condyle: A Case Series with up to 9-Year Follow-Up.

We demonstrated the safety and efficacy of autologous chondrocyte precursor (CP) cell therapy in repairing Grade 4 cartilage defects of medial femoral condyles. The autologous bone marrow mesenchymal stem cells of each participant were isolated, amplified, and then differentiated into CPs in atelocollagen. Neotissues made of CPs were implanted into cartilage defects with an average cell density of 4.9 ± 2.1 × 106 cells/cm2 through arthrotomy. The knee function was evaluated with the International Knee Documentation Committee (IKDC) subjective knee form. Patients' knee functions significantly improved by the 28th week (IKDC score = 68.3 ± 12.1), relative to the initial functionality before the CP therapy (IKDC score = 46.1 ± 16.4, p-value = 0.0014). Nine of these twelve patients maintained good knee functions for 9 years post-implantation (IKDC score = 69.8 ± 12.3) at levels higher than the pre-implantation values (p-value = 0.0018). Patients were evaluated with MRI and arthroscopy, and the defective sites exhibited a smooth surface without a gap between the implant and host tissue. This study demonstrates that autologous CPs successfully engraft into the host tissue and result in the re-formation of hyaline-like cartilage, thereby improving the impaired knee functions. Most importantly, no adverse event was reported during this long-term follow-up period.

Prediction of Lumbar Disc Bulging and Protrusion by Anthropometric Factors and Disc Morphology.

The relationship between reduced disc height and disc bulging and/or protrusion has been controversial. The purposes of this study were to examine the relationship between disc morphology and disc bulging and protrusion and to establish a model for predicting disc bulging and protrusion. This is a retrospective study. A total of 452 MRI scans from a spine study were analysed, 210 (46.5%) were men. Logistic regression analysis was applied to identify the association between anthropometric factors, disc morphology factors, and outcome. Model 1 was constructed using anthropometric variables to investigate the capacity for predicting outcomes. Model 2 was constructed using anthropometric and disc morphology variables. Age, body weight, body height, disc height, and disc depth were significantly associated with outcome. The area under the curve (AUC) statistics of Model 2 were significantly better than those of Model 1 at the L3-L4 and L4-L5 levels but not at the L5-S1 level. The results showed an association between disc morphology and disc bulging and/or protrusion at the L3-L4, L4-L5, and L5-S1 levels. The model utilizing both anthropometric factors and disc morphology factors had a better capacity to predict disc bulging and/or protrusion compared with the model using only anthropometric factors.

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

BACKGROUND: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use. METHODS: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered. RESULTS: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies. CONCLUSION: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.

PET/MRI in Cervical Cancer: Associations Between Imaging Biomarkers and Tumor Stage, Disease Progression, and Overall Survival.

BACKGROUND: Positron emission tomography (PET)/MRI biomarkers have been shown to have prognostic significance in patients with cervical cancer. Their associations with progression-free survival (PFS) and overall survival (OS) merit further investigation. PURPOSE: To evaluate the association between PET/MRI biomarkers and tumor stage, PFS, and OS in patients with cervical cancer. STUDY TYPE: Prospective cohort study. POPULATION: In all, 54 patients with newly diagnosed cervical cancer and measurable tumors (>1 cm) were included in the image analysis. FIELD STRENGTH/SEQUENCE: 3.0T integrated PET/MRI including diffusion-weighted echo-planar imaging (b = 50 and 1000 s/mm2 ) and [18F]fluorodeoxyglucose PET. ASSESSMENT: Two radiologists measured the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean ), maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. STATISTICAL TESTS: A Mann-Whitney U-test was used to evaluate the association between the imaging biomarkers and tumor stage. A Cox proportional hazards model was used to assess the relationships between the imaging biomarkers and survival. RESULTS: In advanced tumors (T ≥ 1b2, M1, stage ≥ IB3), ADCmin was significantly lower and MTV, TLG, MTV/ADCmin , and TLG/ADCmin were significantly higher (P values between <0.001 and 0.036). In N1 tumors, ADCmin was significantly lower and MTV and MTV/ADCmin were significantly higher (P values between 0.005 and 0.016). In survival analysis, SUVmax was an independent predictor of PFS (hazard ratio [HR] = 4.57, P < 0.05), and ADCmin was an independent predictor of OS (HR = 0.02, P < 0.05). In subgroup analysis of patients with different stages, MTV/ADCmin was a predictor of PFS in stage I disease (P = 0.003), ADCmin (P = 0.038), and MTV (P = 0.020) in stage II, SUVmax (P = 0.006), and TLG (P = 0.006) in stage IV; and ADCmin was a predictor of OS in stage III disease (P = 0.008). DATA CONCLUSION: PET/MRI biomarkers of cervical cancer are associated with tumor stage and survival. SUVmax and ADCmin are independent predictors of PFS and OS, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 3.

Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF. METHODS: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured. RESULTS: One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926). CONCLUSIONS: Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery. CLINICAL TRIAL NUMBER: NCT01312012 (ClinicalTrials.gov) LAY SUMMARY: Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.