Correlation of Non-tumoral Liver Dose with Treatment-Related Adverse Events in Patients with Hepatocellular Carcinoma Treated with Glass-Based Yttrium-90 Radioembolization.

PURPOSE: To evaluate the relationship between non-tumor liver (NTL) dose and adverse events (AE) in patients with hepatocellular carcinoma (HCC) treated with glass-based Yttrium-90 radioembolization (Y90-RE). MATERIALS AND METHODS: A retrospective analysis of patients with HCC treated with Y90-RE between 2013 and 2018 was performed. Baseline characteristics including demographics and Y90-RE treatment approach were captured. Common Terminology Criteria for Adverse Events v5 was assessed at months 3 and 6 post-treatment. Using voxel-based dosimetry with MIM Software V. 6.9, dose-volume histograms of treated area of liver were created. Receiver operator characteristic curve was used to determine NTL dose threshold predicting AEs. Multivariate analysis was used to determine independent clinical factors of predicting severe AEs. Chi-square analysis was used to compare proportions. RESULTS: Two hundred and twenty-nine consecutive patients (115(50.2%) lobar and 114(49.8%) segmental) were included. At 3 months, there was a lower rate of any grade AE (55(46%) segmental and 36(31%) lobar, p = 0.009) and increased rate of severe AEs for lobar compared to segmental (2(2%) segmental and 9(8%) lobar, p = 0.029). At 6 months, severe AEs were greater for lobar than segmental (1(1%) segmental vs 10(9%) lobar, p = 0.005). For lobar Y90-RE, mean NTL dose of 112 Gy predicted severe AE (89% sensitivity and 91% specificity (AUC = 0.95, p = < 0.0001) at 3 and 6 months. For the segmental group, no significant association was found between NTL dose and severe treatment-related AE at 3 and 6 months. CONCLUSION: In patients with HCC undergoing glass-based lobar Y90-RE, NTL dose of > 112 Gy is associated with severe treatment-related AEs at 3-6 months.

Microwave Ablation as Bridging to Liver Transplant for Patients with Hepatocellular Carcinoma: A Single-Center Retrospective Analysis.

PURPOSE: To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant. MATERIALS AND METHODS: This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and who were listed for liver transplantation at a single medical center between 2011 and 2019. The overall survival (OS) rate statuses after liver transplant, waitlist retention, and disease progression were evaluated using the Kaplan-Meier techniques. RESULTS: Among the 88 patients (72 men and 16 women; mean age, 60 years; Model for End-Stage Liver Disease score, 11.2) who were listed for transplant, the median waitlist time was 9.4 months (interquartile range, 5.5-18.9). Seventy-one (80.7%) patients received transplant after a median waitlist time of 8.5 months. Seventeen (19.3%) patients were removed from the waitlist; of these, 4 (4.5%) were removed because of tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or alpha-fetoprotein was observed in the transplanted versus nontransplanted patients at the time of ablation (2.1 vs 2.1 cm and 34.4 vs 34.7 ng/mL for transplanted vs nontransplanted, respectively; P > .05). Five (5.1%) of the 88 patients experienced adverse events after ablation; however, they all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The OS status after liver transplant at 5 years was 76.7%, and the disease-specific survival after LTP was 89.6%, with a median follow-up of 61 months for all patients. CONCLUSIONS: MW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or LTP.

Management of uncomplicated total knee arthroplasty chronic pain and stiffness utilizing cooled radiofrequency ablation: a single institution pilot study.

OBJECTIVE: The objective of this study is to introduce cooled radiofrequency ablation technical feasibility as an alternative percutaneous image-guided treatment of chronic pain and stiffness in the setting of uncomplicated total knee arthroplasty. MATERIAL AND METHOD: This retrospective pilot study includes a total of 19 consecutive patients experiencing persistent chronic pain after total knee arthroplasty, without underlying hardware complications who had failed conservative care. Patients initially underwent anesthetic blocks of the genicular nerve branches to determine C-RFA candidacy. After adequate response to the anesthetic blocks (> 50% immediate pain relief), patients were subjected to cooled radiofrequency ablations 2-3 weeks later. Treatment response was evaluated utilizing clinically validated questionnaires (KOOS, the Knee Injury and Osteoarthritis Outcome Score) and visual analog scale (VAS) to assess pain severity, stiffness, functional activities of daily living, and use of pain medication. Follow-up outcome scores were collected up to 1 year after C-RFA procedure. RESULT: A total of 21 knees were treated consecutively between 4/2019 and 1/2020 (mean age 70.5 years; 5 M:14F). The mean total KOOS score improved significantly from baseline at 35.0 ± 14.0 to 64.2 ± 14.7 at a mean of 10.2 months after treatment (p < 0.0001), with significant improvement in mean stiffness score from 44.8 ± 16.7 to 68.8 ± 20 (p < 0.0001). The mean VAS score improved significantly from baseline at 8.30 ± 1.1 to 2.45 ± 1.8 (p < 0.0001). No major complications were encountered. No patients went on to receive re-treatment, surgical revision, or other intervention. CONCLUSION: Image-guided genicular nerve cooled radiofrequency ablation offers a promising alternative in treating chronic pain/stiffness in the setting of uncomplicated TKA.

Predictors of Successful Yttrium-90 Radioembolization Bridging or Downstaging in Patients with Hepatocellular Carcinoma.

Purpose: This study aims to identify clinical and imaging prognosticators associated with the successful bridging or downstaging to liver transplantation (LT) in patients undergoing Yttrium-90 radioembolization (Y90-RE) for hepatocellular carcinoma (HCC). Methods: Retrospectively, patients with Y90-RE naïve HCC who were candidates or potential candidates for LT and underwent Y90-RE were included. Patients were then divided into favorable (maintained or achieved Milan criteria (MC) eligibility) or unfavorable (lost eligibility or unchanged MC ineligibility) cohorts based on changes to their MC eligibility after Y90-RE. Penalized logistic regression analysis was performed to identify the significant baseline prognosticators. Results: Between 2013 and 2018, 135 patients underwent Y90-RE treatment. Among the 59 (42%) patients within MC, LT eligibility was maintained in 49 (83%) and lost in 10 (17%) patients. Within the 76 (56%) patients outside MC, eligibility was achieved in 32 (42%) and unchanged in 44 (58%). Among the 81 (60%) patients with a favorable response, 16 (20%) went on to receive LT. Analysis of the baseline characteristics revealed that lower Albumin-Bilirubin score, lower Child-Pugh class, lower Barcelona Clinic Liver Cancer stage, HCC diagnosis using dynamic contrast-enhanced imaging on CT or MRI, normal/higher albumin levels, decreased severity of tumor burden, left lobe HCC disease, and absence of HBV-associated cirrhosis, baseline abdominal pain, or fatigue were all associated with a higher likelihood of bridging or downstaging to LT eligibility (p's < 0.05). Conclusion: Certain baseline clinical and tumor characteristics are associated with the successful bridging or downstaging of potential LT candidates with HCC undergoing Y90-RE.

Supporting the improvement of air quality management practices: The "FAIRMODE pilot" activity.

This paper presents the first outcomes of the "FAIRMODE pilot" activity, aiming at improving the way in which air quality models are used in the frame of the European "Air Quality Directive". Member States may use modelling, combined with measurements, to "assess" current levels of air quality and estimate future air quality under different scenarios. In case of current and potential exceedances of the Directive limit values, it is also requested that they "plan" and implement emission reductions measures to avoid future exceedances. In both "assessment" and "planning", air quality models can and should be used; but to do so, the used modelling chain has to be fit-for-purpose and properly checked and verified. FAIRMODE has developed in the recent years a suite of methodologies and tools to check if emission inventories, model performance, source apportionment techniques and planning activities are fit-for-purpose. Within the "FAIRMODE pilot", these tools are used and tested by regional/local authorities, with the two-fold objective of improving management practices at regional/local scale, and providing valuable feedback to the FAIRMODE community. Results and lessons learnt from this activity are presented in this paper, as a showcase that can potentially benefit other authorities in charge of air quality assessment and planning.

Combination transarterial chemoembolization and microwave ablation improves local tumor control for 3- to 5-cm hepatocellular carcinoma when compared with transarterial chemoembolization alone.

PURPOSE: To compare transarterial chemoembolization (TACE) monotherapy to combination TACE and microwave ablation (MWA) for local control of 3- to 5-cm hepatocellular carcinoma (HCC). METHODS: Patients with HCC between 3 and 5 cm treated with TACE monotherapy or combination TACE + MWA at a single institution between 2007 and 2016 were retrospectively reviewed. Twenty-four HCCs (median diameter 3.8 cm) in 16 patients (13 males; median age 64 years) were treated using TACE monotherapy. Combination TACE + MWA was used to treat 23 HCCs (median diameter 4.2 cm) in 22 patients (18 males; median age 61 years). Microwave ablation was performed at a target time of two weeks following TACE. Individual tumors were followed by serial contrast-enhanced CT or MR. Response to treatment was evaluated on a tumor-by-tumor basis using mRECIST criteria with the primary outcome being local tumor progression (LTP). Data were analyzed using Fisher's exact test for categorical variables and Wilcoxon rank sum test for continuous variables. Time to LTP was estimated with the Kaplan-Meier method. RESULTS: Relative to TACE monotherapy, TACE + MWA provided a trend toward both a lower rate of LTP (34.8% vs. 62.5%, p = 0.11) and a higher complete response rate (65.2% vs. 37.5%; p = 0.12). Time to LTP (22.3 months vs. 4.2 months; p = 0.001) was significantly longer in the TACE + MWA group compared to TACE monotherapy. CONCLUSIONS: Combination therapy with TACE and microwave ablation improves local control and increases time to LTP for 3-5 cm HCC.

Robotically Assisted Sonic Therapy as a Noninvasive Nonthermal Ablation Modality: Proof of Concept in a Porcine Liver Model.

Purpose To determine the feasibility of creating a clinically relevant hepatic ablation (ie, an ablation zone capable of treating a 2-cm liver tumor) by using robotically assisted sonic therapy (RAST), a noninvasive and nonthermal focused ultrasound therapy based on histotripsy. Materials and Methods This study was approved by the institutional animal use and care committee. Ten female pigs were treated with RAST in a single session with a prescribed 3-cm spherical treatment region and immediately underwent abdominal magnetic resonance (MR) imaging. Three pigs (acute group) were sacrificed immediately following MR imaging. Seven pigs (chronic group) were survived for approximately 4 weeks and were reimaged with MR imaging immediately before sacrifice. Animals underwent necropsy and harvesting of the liver for histologic evaluation of the ablation zone. RAST ablations were performed with a 700-kHz therapy transducer. Student t tests were performed to compare prescribed versus achieved ablation diameter, difference of sphericity from 1, and change in ablation zone volume from acute to chronic imaging. Results Ablation zones had a sphericity index of 0.99 ± 0.01 (standard deviation) (P < .001 vs sphericity index of 1). Anteroposterior and transverse dimensions were not significantly different from prescribed (3.4 ± 0.7; P = .08 and 3.2 ± 0.8; P = .29, respectively). The craniocaudal dimension was significantly larger than prescribed (3.8 ± 1.1; P = .04), likely because of respiratory motion. The central ablation zone demonstrated complete cell destruction and a zone of partial necrosis. A fibrous capsule surrounded the ablation zone by 4 weeks. On 4-week follow-up images, ablation zone volumes decreased by 64% (P < .001). Conclusion RAST is capable of producing clinically relevant ablation zones in a noninvasive manner in a porcine model. © RSNA, 2018.

Real-world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis.

BACKGROUND: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile. MATERIAL AND METHODS: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). RESULTS: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105 /mm3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). CONCLUSIONS: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count.

Microwave Ablation of the Lung in a Porcine Model: Vessel Diameter Predicts Pulmonary Artery Occlusion.

PURPOSE: To determine the size of pulmonary artery (PA) at risk for occlusion during percutaneous microwave ablation and to assess the effect of vessel diameter, number, and patency, on ablation zone volume. MATERIALS AND METHODS: Computed tomography (CT) fluoroscopy-guided percutaneous microwave ablations were performed in 8 pigs under general anesthesia. All ablations were performed at 65 W for 5 min with a single 17-gauge antenna positioned in the central third of the lungs. A CT pulmonary angiogram was performed immediately after the ablations. The maximum diameter, number and patency of PA branches within each ablation zone were recorded. Ablation volumes were measured at gross dissection and with CT. Student's t test was used to compare ablation zone volumes among groups. RESULTS: Twenty-one pulmonary ablations were performed. Six of the ablation zones (29%) contained at least 1 occluded PA branch. The mean diameter of the occluded PA branches in the ablation zones (2.4 mm; range, 2.0-2.8 mm) was significantly smaller than non-occluded PA branches (3.7 mm; range: 2.1-6.9 mm; p = 0.009). No PA branches ≥3 mm in size were occluded. There was no significant difference in volume of gross ablation zones that contained occluded versus non-occluded PAs (p = 0.42), one versus multiple PAs (p = 0.71), or PAs <3 mm versus ≥3 mm in diameter (p = 0.44). CONCLUSIONS: PAs ≥3 mm in size have a low risk for iatrogenic occlusion during percutaneous microwave ablation. The presence of multiple adjacent PA branches, an occluded PA branch, and a vessel diameter ≥3 mm within the ablation zone had no observed effect on ablation zone volume.

Early Prediction of Sepsis Incidence in Critically Ill Patients Using Specific Genetic Polymorphisms.

Several diagnostic methods for the evaluation and monitoring were used to find out the pro-inflammatory status, as well as incidence of sepsis in critically ill patients. One such recent method is based on investigating the genetic polymorphisms and determining the molecular and genetic links between them, as well as other sepsis-associated pathophysiologies. Identification of genetic polymorphisms in critical patients with sepsis can become a revolutionary method for evaluating and monitoring these patients. Similarly, the complications, as well as the high costs associated with the management of patients with sepsis, can be significantly reduced by early initiation of intensive care.

Recent insights into the molecular pathogenesis of Crohn's disease: a review of emerging therapeutic targets.

Chronic inflammatory bowel diseases (IBDs) are a subject of great interest in gastroenterology, due to a pathological mechanism that is difficult to explain and an optimal therapeutic approach still undiscovered. Crohn's disease (CD) is one of the main entities in IBD, characterized by clinical polymorphism and great variability in the treatment response. Modern theories on the pathogenesis of CD have proven that gut microbiome and environmental factors lead to an abnormal immune response in a genetically predisposed patient. Genome-wide association studies in patients with CD worldwide revealed several genetic mutations that increase the risk of IBD and that predispose to a more severe course of disease. Gut microbiota is considered a compulsory and an essential part in the pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different bacterial strains can be found in all patients with IBD. The discovery of Escherichia coli entero-invasive on resection pieces in patients with CD now increases the likelihood of antimicrobial or vaccine-type treatments. Recent studies targeting intestinal immunology and its molecular activation pathways provide new possibilities for therapeutics. In addition to antitumor necrosis factor molecules, which were a breakthrough in IBD, improving mucosal healing and resection-free survival rate, other classes of therapeutic agents come to focus. Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent cellular immune response. In addition to anti-integrin antibodies, chemokine receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging results in clinical trials. Micro-RNAs have demonstrated their role as disease biomarkers but it could also become useful for the treatment of IBD. Moreover, cellular therapy is another therapeutic approach under development, aimed for severe refractory CD. Other experimental treatments include intravenous immunoglobulins, exclusive enteral nutrition, and granulocyte colony-stimulating factors.

Microwave Ablation for the Treatment of Hepatic Adenomas.

Microwave (MW) ablation was used to treat 12 hepatocellular adenomas in six patients (five women and one man; mean age, 39.6 y). Mean treated tumor size was 2.7 cm ± 2.0. Tumor response was evaluated with serial cross-sectional imaging for a mean follow-up of 12.6 months ± 7.1. Primary treatment effectiveness and local tumor control were 100%. There were no instances of hemorrhage, malignant transformation, new hepatic tumors, or extrahepatic metastases. This early experience of treatment of hepatic adenomas by MW ablation demonstrates it to be a safe and feasible treatment modality at short-term follow-up. Continued investigation, including comparison with other treatment modalities, is warranted.

Prevalence and impact on survival of hepatopulmonary syndrome and cirrhotic cardiomyopathy in a cohort of cirrhotic patients.

BACKGROUND & AIMS: Extrahepatic complications of cirrhosis increase the risk for decompensation of the liver disease and death. Previous studies show common pathogenetic mechanisms involved in the development of hepatopulmonary syndrome and cirrhotic cardiomyopathy. We aimed to assess the link between these entities and their effect on disease-related patient morbidity and mortality. METHODS: Seventy-four consecutive cirrhotic patients without prior history of cardiovascular and pulmonary disease were included in a prospective observational study. Routine blood work, arterial blood gas analysis, pulse oximetry measurements, N-terminal pro-brain natriuretic peptide levels and contrast enhanced echocardiography examination with tissue Doppler imaging were performed in all patients. Patients were followed up for a median of 6 months and disease-related adverse events and death were the main outcomes tested. Statistical analysis was conducted according to the presence of hepatopulmonary syndrome or cirrhotic cardiomyopathy. RESULTS: Hepatopulmonary syndrome was diagnosed in 17 patients (23%) and cirrhotic cardiomyopathy in 30 patients (40.5%). There was no association between the presence of cirrhotic cardiomyopathy and the existence of mild or moderate hepatopulmonary syndrome. No echocardiographic parameters were useful in predicting the presence of hepatopulmonary syndrome. N-terminal pro-brain natriuretic peptide levels and length of QT interval did not aid in diagnosis of cirrhotic cardiomyopathy. Neither entity had significant influence on disease-related outcomes in the follow-up period. CONCLUSIONS: Hepatopulmonary syndrome and cirrhotic cardiomyopathy are independent complications arising in cirrhosis and have a limited influence on morbidity and mortality on a pre-liver transplantation population.

Vertebral body osteolysis following the use of bone morphogenetic protein in spinal surgery: a mimicker of infection.

This report describes the imaging findings in three patients who developed lumbar spine osteolysis after posterior spinal fusion using rhBMP-2. These cases demonstrate the variable course of osteolysis, as well as the importance of recognizing its radiological appearances to prevent confusion with infection following spinal fusion.

Nuclear Division Index may Predict Neoplastic Colorectal Lesions.

BACKGROUND: Colorectal cancer (CRC) develops by accumulation of multiple genetic damages leading to genetic instability that can be evaluated by cytogenetic methods. In the current study we used Cytokinesis-Blocked Micronucleus Assay (CBMN) technique to assess the behavior of Nuclear Division Index(NDI) in peripheral lymphocytes of patients with CRC and polyps versus patients with normal colonoscopy. METHODS: Blood samples were collected from patients after informed consent. By CBMN technique we assessed the proportion of mono-nucleated, bi-nucleated, tri-nucleated and tetra-nucleated cells/500 cells, to calculate NDI. Data were statistically analyzed using the SPSS 11.0 package. RESULTS: 45 patients were available for analysis, 23 men and 22 women, with a mean age of 58.7±13.5. 17 had normal colonoscopy, 17 colonic polyps and 11 CRC. The mean NDI values were significantly smaller for patients with CRC or polyps than in patients with normal colonoscopy (1.57 vs 1.73, p=0.013). The difference persisted for patients with neoplastic lesions (adenomas and carcinomas) when compared with patients with normal colonoscopy or non neoplastic (hyperplastic) polyps (1.56 vs.1.71, p=0.018). The NDI cut-off value to predict the presence of adenomas or carcinomas was equal to 1.55 with a 54.2% sensitivity and 81% specificity of lower values (p=0.019). The NDI cut off value to predict the presence of advanced adenomas or cancer was 1.525 for a sensitivity of 56.3% and a specificity of 82.8% (p=0.048). CONCLUSION: NDI may be useful in screening strategies for colorectal cancer as simple, noninvasive, inexpensive cytogenetic biomarker.

Effect of peri-modiolar cochlear implant positioning on auditory nerve responses: a neural response telemetry study.

CONCLUSIONS: There was no evidence that a reduction in current was needed for nerve stimulation as a result of modiolar placement of a cochlear implant. However, modiolus hugging did reduce the spread of excitation for the basal and apical electrodes. This improved stimulation selectivity may result in improved speech discrimination by implant users. OBJECTIVE: To test the effect of modiolar placement of a cochlear implant on stimulation thresholds, and to confirm whether peri-modiolar electrode placement resulted in the hypothesized reduced spread of excitation. MATERIAL AND METHODS: Auditory nerve responses were measured by means of neural response telemetry (NRT) in 14 subjects. All subjects received a Nucleus CI24R(CS) Contour implant. For each subject, the stimulation threshold and response growth rate were determined on all the odd-numbered electrodes, using a masker-and-probe paradigm. In addition, the spatial spread of excitation was measured on electrodes 1, 6, 11, 16 and 20, using a variable-masker paradigm. All NRT measurements were performed intra-operatively, both before and after peri-modular placement of the electrode by removal of surgical stylet. RESULTS: Removal of the stylet had no significant effect on the threshold and growth rate of NRT responses. It caused a reduction in the spread of excitation for electrodes 1, 6 and 20, but not for electrodes 11 and 16.