Combination and Optimal Sequencing of Systemic and Locoregional Therapies in Hepatocellular Carcinoma: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel.

Hepatocellular carcinoma, historically, has had a poor prognosis with very few systemic options. Furthermore, most patients at diagnosis are not surgical candidates. Therefore, locoregional therapy (LRT) has been widely used, with strong data supporting its use. Over the last 15 years, there has been progress in the available systemic agents. This has led to the updated Barcelona Clinic Liver Cancer (BCLC) algorithm's inclusion of these new systemic agents, with advocacy of earlier usage in those who progress on LRT or have tumor characteristics that make them less likely to benefit from LRT. However, neither the adjunct of LRT nor the specific sequencing of combination therapies is addressed directly. This Research Consensus Panel sought to highlight research priorities pertaining to the combination and optimal sequencing of LRT and systemic therapy, assessing the greatest needs across BCLC stages.

Combination of Doxorubicin and Antiangiogenic Agents in Drug-Eluting Beads: In Vitro Loading and Release Dynamics in View of a Novel Therapeutic Approach for Hepatocellular Carcinoma.

PURPOSE: Antiangiogenic agents have been used for many years as a first-line systemic treatment for advanced HCC. Embolization with cytostatic drugs on the other hand is the first-line treatment for intermediate HCC. The two types of drugs have not been combined for intraarterial delivery yet. The loading and release dynamics and the in vitro effect of their combination are tested in this experimental study. MATERIALS AND METHODS: Drug-eluting beads were loaded with doxorubicin, sunitinib and sunitinib analogue piperazine (SAP) alone and with their combinations. Diameter change, loading, release, and effect in cellular proliferation were assessed. RESULTS: The average microsphere diameter after loading was 473.7 µm (µm) for Doxorubicin, 388.4 µm for Sunitinib, 515.5 µm for SAP, 414.8 µm for the combination Doxorubicin/Sunitinib and 468.8 µm for the combination Doxorubicin /SAP. Drug release in 0.9% NaCl was 10% for Doxorubicin, 49% for Sunitinib, 25% for SAP, 20%/18% for the combination Doxorubicin/Sunitinib, and 18%/23% for the combination Doxorubicin/SAP whereas in human plasma it was 56%, 27%, 13%, 76%/63% and 62%/15%, respectively. The mean concentration of Doxorubicin that led to inhibition of 50% of cellular proliferation in an HCC Huh7 cell line was 163.1 nM (nM), for Sunitinib 10.3 micromolar (µΜ), for SAP 16.7 µΜ, for Doxorubicin/Sunitinib 222.4 nM and for Doxorubicin/SAP 275 nM. CONCLUSIONS: Doxorubicin may be combined with antiangiogenic drugs with satisfactory in vitro loading and release outcomes and effect on cellular lines.

Comparison of pulmonary and small airways function between idiopathic inflammatory myopathies patients with and without interstitial lung disease.

OBJECTIVES: To evaluate pulmonary and small airway function in patients with idiopathic inflammatory myopathies (IIM) and make comparisons between patients with and without interstitial lung disease (ILD). METHODS: Newly diagnosed IIM patients with and without ILD determined by high resolution computed tomography were included in the study. Pulmonary and small airway function was assessed by spirometry, diffusing capacity for carbon monoxide (DLCO), body plethysmography, single and multiple breath nitrogen washout, impulse oscillometry and measurement of respiratory resistance by the interrupter technique (Rint) using the Q-box system. We used discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography to evaluate for small airway dysfunction. RESULTS: Study cohort comprised of 26 IIM patients, 13 with and 13 without ILD. IIM-ILD patients presented more frequently with dyspnoea, fever, arthralgias and positive anti-synthetase antibodies, compared to IIM patients without ILD. Classic spirometric parameters and most lung physiology parameters assessing small airway function did not differ between the two groups. Predicted total lung capacity and residual volume (TLCN2WO, RVN2WO) measured by multiple breath nitrogen washout and the TLCN2WO/TLCpleth ratio were significantly lower in IIM-ILD patients compared to those without ILD (mean: 111.1% vs. 153.4%, p=0.034, median: 171% vs. 210%, p=0.039 and median: 1.28 vs. 1.45, p=0.039, respectively). Rint tended to be higher among IIM-ILD patients (mean:100.5% vs. 76.6%, p=0.053). CONCLUSIONS: Discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography in IIM-ILD patients indicate an early small airways dysfunction in these patients.

Angiographic Imaging of Prostatic Artery Origin in a Greek Population and Correlation With Technical and Clinical Aspects of Prostatic Artery Embolization.

Background This study aimed, first, to angiographically investigate and analyze prostatic artery (PA) origin in a Greek male population with benign prostatic hyperplasia (BPH) treated with prostatic artery embolization (PAE) and, second, to correlate prostatic arterial anatomy with technical and clinical aspects of PAE. Methodology This was a retrospective study of BPH patients who underwent PAE in a single tertiary center in Greece from June 2019 to July 2022. For the first part of the study, PA was imaged with computed tomography angiography (CTA) before PAE and with digital subtraction angiography (DSA) during PAE in all patients. A widely accepted system for the classification of PA origin was applied. Type I, a common origin of PA and superior vesical artery (SVA) from the anterior division of internal iliac artery (IIA). Type II, PA originating from the anterior division of IIA, separate from, and inferior to SVA. Type III, the origin of PA from the obturator artery. Type IV, the origin of PA from the internal pudendal artery. Type V, rarer origins of PA. For the second part of the study, a subgroup of patients from the first part (treated with the same PAE protocol and free of vascular pathology that could have interfered with the technical success of PAE) was selected. In this subgroup, differences in PA origin were correlated with technical aspects (feasibility of catheterization of PA, fluoroscopy time (FT), dose area product (DAP)) and clinical outcomes of PAE. Results After the exclusion of four patients, 159 patients were included in the first part of the study. From a total of 355 PAs, 110 (31%) were compatible with type I, 58 (16.3%) type II, 45 (12.7%) type III, 110 (31%) type IV, and 32 (9%) type V. PA origin from an accessory internal pudendal artery was the most common among the rare origins of type V. Regarding the second part of the study (a subgroup of 101 patients selected to facilitate comparisons between the different types of PA origin), type I was associated with significantly more incidences of failed or difficult catheterization of the PA compared to all other types combined (27/64 vs. 18/138, p < 0.001). Types III, IV, and V showed a relatively low degree of technical difficulty. Patients with type I PA origin of at least one pelvic side (subgroup (I), n = 48) had significantly longer FT and DAP compared to the rest (subgroup (O), n = 53). Clinical success rates of PAE were slightly lower for the subgroup (I), although the difference was not statistically significant (75.8% vs. 83.8% at 18 months post-PAE, p = 0.137). No major complications were observed. Conclusions This is the first study of PA origin in Greece. It was demonstrated that types I and IV of PA origin were the most common and had the same prevalence. Type I showed significantly higher technical difficulty compared to the others, but had no significant impact on the clinical outcomes of PAE.

Percutaneous thrombin injection under contrast-enhanced ultrasound guidance to control active extravasation not associated with pseudoaneurysm.

The technique of percutaneous thrombin injection (PTI) under contrast-enhanced ultrasound (CEUS) guidance for control of acute hemorrhage-active extravasation not associated with pseudoaneurysm is demonstrated in three cases: 1) Massive spontaneous retroperitoneal hematoma in a patient with multiple comorbidities. Contrast-enhanced computed tomography (CT) showed extensive active extravasation, which was only partially controlled by transarterial embolization. CEUS was performed in the angiography suite. Contrary to unenhanced US and colour Doppler US (CDUS), CEUS confirmed persistent extravasation; CEUS-guided PTI was performed immediately thereafter. 2) Large rectus sheath hematoma in a patient on anticoagulant therapy. Contrast-enhanced CT and unenhanced US/CD could not definitely diagnose extravasation. CEUS clearly showed extravasation and was used for guidance of PTI. 3) Chest wall hematoma complicating central venous catheter placement in a patient with coronavirus on anticoagulant therapy. CDUS was inconclusive. CEUS was performed at the bedside, clearly showed active extravasation, and was used for guidance of PTI. In all three cases, post-PTI CEUS confirmed the absence of residual enhancement of the hematomas, and the hemodynamic status of the patients improved. PTI appears to be effective in selected cases of hematomas associated with active extravasation. In this context, CEUS may be the most suitable modality for guidance and for an immediate evaluation of the treatment effect.

Transarterial Chemoembolization with Anthracyclines-Loaded Polyethylene Glycol Drug Eluting Microspheres for the Treatment of Hepatocellular Carcinoma: A Pooled Multicentric Analysis of Survival in 580 Patients.

PURPOSE: To evaluate survival, efficacy and safety of transarterial chemoembolization (TACE) in the treatment of patients with hepatocellular carcinoma (HCC), through a pooled analysis of patients with BCLC 0, A and B HCC stages, treated with polyethylene glycol drug eluting microspheres (PEG-DEM) TACE. MATERIALS AND METHODS: Patients from 3 retrospective and 2 prospective registries were included. Overall survival (OS), progression-free survival (PFS), tumour response and safety were evaluated. Multivariate Cox regression analysis was performed to evaluate predictors of OS. RESULTS: A total of 580 patients (72.1% males, mean age 66.9 ± 10.3 years) were included. 43.5% had BCLC A, and 41.0% BCLC B disease stage, and 85.8% were Child-Pugh class A. Complete and partial response (mRECIST or RECIST1.1) were achieved in 60.14% and 27.11% of patients, with overall response and disease control rates of 87.30% and 94.60%, respectively. Median OS was 50.8 months for the total population, and 61.2 and 38.1 months for BCLC 0 + A and BCLC B patients, respectively. Median PFS for the total population, BCLC 0 + A and BCLC B groups was 15.6, 21.6 and 12.7 months, respectively. CONCLUSIONS: This multicentric pooled analysis confirmed efficacy and safety of PEG-DEM TACE, with a median OS of 50.8 months.

Small airways dysfunction in patients with systemic sclerosis and interstitial lung disease.

Background: A number of studies report small airways involvement in patients with systemic sclerosis (SSc). Furthermore, small airways dysfunction is increasingly recognized in patients with interstitial lung disease (ILD) of idiopathic or autoimmune etiology. The objectives of this study were to evaluate small airways function in SSc patients with ILD and explore the effect of treatment on small airways function by using conventional and contemporary pulmonary function tests (PFTs). Methods: This single-center, prospective, observational study included a total of 35 SSc patients, with and without ILD based on HRCT scan, evaluated by a special radiologist blindly. Clinical data were collected from all patients who were also assessed for HRCT findings of small airways disease. Small airways function was assessed by classic spirometry, measurement of diffusing capacity for carbon monoxide, body plethysmography, single breath nitrogen washout (N2SBW) and impulse oscillometry (IOS). The prevalence of small airways dysfunction according to R5-R20, phase III slopeN2SBW and CV/VC methodologies was calculated in the total SSc population. Pulmonary function tests were compared between: (a) SSc-ILD and non-ILD patients and (b) two time points (baseline and follow up visit) in a subset of SSc-ILD patients who received treatment for ILD and were re-evaluated at a follow up visit after 12 months. Results: Phase III slopeN2SBW and R5-R20 showed the highest diagnostic performance for detecting small airways dysfunction among SSc patients (61 and 37.5%, respectively). Twenty three SSc patients were found with ILD and 14 of them had a 12-month follow up visit. SSc-ILD patients compared to those without ILD exhibited increased phase III slopeN2SBW ≥120% (p = 0.04), R5-R20 ≥0.07 kPa/L/s (p = 0.025), airway resistance (Raw) (p = 0.011), and special airway resistance (sRaw) (p = 0.02), and decreased specific airway conductance (sGaw) (p = 0.022), suggesting impaired small airways function in the SSc-ILD group. Radiographic features of SAD on HRCT were observed in 22% of SSc-ILD patients and in none of SSc-non-ILD patients. Comparison of PFTs between baseline and follow-up visit after 12 months in the 14 SSc-ILD treated patients, showed improvement of phase III slopeN2SBW (p = 0.034), R5-R20 (p = 0.035) and Raw (p = 0.044) but not sRaw and sGaw parameters. Conclusion: Phase III slopeN2SBW and R5-R20 may reveal small airways dysfunction in SSc associated ILD before structural damage and may be partially improved in a subset of patients receiving treatment for ILD.

A Retrospective, Single-Center Study of Technical-Procedural Factors Affecting Radiation Dose During Prostatic Artery Embolization.

Introduction This study aims to evaluate the effect of technical-procedural factors on radiation dose during prostatic artery embolization (PAE). Methods This was a single-center, retrospective study of 59 patients with benign prostatic hyperplasia (BPH) who underwent prostatic artery embolization from March 2020 to September 2021. Computed tomography angiography (CTA) was performed for vascular planning prior to PAE in all patients. The effect of the following techniques on the dose area product (DAP) of PAE was evaluated: application of low-dose protocol (LDP) for digital subtraction angiography (DSA), reduction of oblique projections by performing PAE of at least one pelvic side utilizing anteroposterior projections only (AP-PAE), utilization of "roadmap" technique instead of DSA for the delineation of pelvic arterial anatomy (RDMP-PAE), and cone-beam CT (CBCT). The impact of the patient's body mass index (BMI) on DAP was also calculated. The effective dose (ED) of PAE and pre-PAE CTA was calculated from DAP and from dose length products, respectively, using appropriate conversion factors. Results For the entire study population (n = 59), the mean DAP of PAE was 16,424.7 ± 8,019 µGy‧m2. On simple regression analysis, LDP, AP-PAE, and RDMP-PAE significantly contributed to DAP reduction during PAE (30% (p = 0.004), 26.7% (p = 0.013), and 31.2% (p = 0.004), respectively). On multiple regression, LDP and AP-PAE maintained their significant effect (p = 0.002 and p = 0.006, respectively). CBCT was associated with a not statistically significant increase in DAP (10.1%) (p = 0.555). The ED of CTA represented 21.2% ± 10.6% of the ED of PAE. Conclusion Of the four studied factors, LDP, AP-PAE, and RDMP-PAE proved to be relatively simple and widely available techniques that could limit radiation exposure of both the operators and the patients during PAE. The contribution of planning CTA to the overall radiation exposure of patients undergoing PAE appears to be not negligible.

Polyethylene Glycol Drug-Eluting Embolic Microspheres Loaded with Doxorubicin for the Treatment of Hepatocellular Carcinoma: Feasibility, Safety, and Pharmacokinetic Study.

PURPOSE: Polyethylene glycol drug-eluting microspheres (PEG-DEMs) can be loaded to elute doxorubicin. The current study evaluated the pharmacokinetic profile and safety of PEG-DEMs in the treatment of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The current prospective, multicenter, dose-escalation study enrolled 25 patients (68% men) with early or intermediate stage HCC and a performance status of 0. Patients in Cohort I were assigned to receive target doxorubicin doses of 75, 100, or 150 mg. Analyses were performed on the basis of the specific dose of doxorubicin that the patients received because some patients received less than the assigned dose. Patients in Cohort II received the maximum safe tested dose. Adverse events were classified according to the Common Terminology Criteria for Adverse Events version 4.03. The tumor response was evaluated every 3 months according to the European Association for the Study of the Liver criteria and modified Response Evaluation Criteria in Solid Tumors. RESULTS: The maximum tested safe dose of doxorubicin was 150 mg. For the groups that received ≤75, 75-100, and 101-150 mg of doxorubicin, the peak plasma concentrations were 286.7 ng/mL ± 220.1, 157.1 ng/mL ± 94.6, and 245.4 ng/mL ± 142.8, respectively; the areas under the curves calculated from 0 to 24 h were 421.7 (ng × h)/mL ± 221.2, 288.1 (ng × h)/mL ± 100.9, and 608.3 (ng × h)/mL ± 319.3, respectively, with almost complete clearance at 24 h. There was no death within 30 d. The best objective response rate was 81%, and the disease control rate was 91%. The median overall survival was 27.2 months (95% confidence interval [CI], 17.5 months to not evaluated [n.e.]); the median progression-free survival was 9.8 months (95% CI, 5.5 months to n.e.). CONCLUSIONS: PEG-DEMs demonstrated a favorable safety profile with low systemic concentration of doxorubicin, and promising efficacy.

Prostatic artery embolization performed in anteroposterior projections versus steep oblique projections: single centre retrospective comparative analysis.

BACKGROUND: To present and evaluate an approach for reduction of utilization of steep oblique angiographic projections during prostatic artery embolization (PAE). METHODS: Single-center, retrospective study of patients who underwent bilateral PAE (from October 2018 to November 2019) and in whom it was possible to embolize PA of at least one pelvic side utilizing anteroposterior projections only (AP-PAE group), with the following techniques: Identification of the origin of PA on anteroposterior angiographic views. Utilization of anatomic landmarks from the planning computed tomographic angiography. Distal advancement of the angiographic catheter or microcatheter in the anterior division of internal iliac artery. Gentle probing with microguidewire at the expected site of origin of the PA. The AP-PAE approach was initially applied to all PAE patients during the study period and when this approach failed, additional steep oblique projections were acquired; patients who underwent bilateral PAE, with both anteroposterior and oblique projections for both pelvic sides, formed the standard PAE (S-PAE) group. The AP-PAE group was compared with S-PAE group in terms of baseline clinical and anatomic features, technical/procedural aspects and outcomes. RESULTS: Forty-six patients (92 pelvic sides) were studied. AP-PAE was feasible in 12/46 patients (26.0%): unilateral AP-PAE in 9/46 patients (19.5%); bilateral AP-PAE in 3/46 patients (6.5%). AP-PAE group had larger prostates (p = 0.047) and larger PAs (p < 0.001). Body mass index (BMI) and other baseline features were comparable between the two groups (mean BMI, AP-PAE group: 27.9 ± 3.6, S-PAE group: 27.0 ± 3.5, p = 0.451). Mean fluoroscopy time and dose area product were lower in AP-PAE group (46.3 vs 57.9 min, p = 0.084 and 22,924.9 vs 35,800.4 µGy.m2, p = 0.018, respectively). Three months post PAE, comparable clinical success rates (11/12 vs 31/34, p = 0.959) and mean International Prostate Symptom Score reduction (60.2% vs 58.1%, p = 0.740) were observed for AP-PAE and for S-PAE group, respectively. No major complications were encountered. CONCLUSION: AP-PAE is associated with significant reduction in radiation exposure and appears to be feasible, safe and effective, but it can be applied in a relatively small percentage of patients.

Sonographic evaluation of prostatic artery embolization: Far beyond size measurements.

Prostatic artery embolization (PAE) has gained acceptance as a minimally invasive, safe and effective treatment of symptomatic benign prostatic hyperplasia. Radiologic imaging is an indispensable part of post-interventional evaluation of PAE and serves both clinical and investigational purposes. In this context, ultrasonography (US) has a central and multifaceted role. Gray-scale US is routinely utilized for measurement of significant outcome parameters (prostatic volume, intra-vesical prostatic protrusion and post-void residual volume) before and after PAE. Improvement of these parameters may become more obvious one-month post-PAE, or later. Contrast-enhanced US (CEUS) with intravenous administration of a second-generation echo-enhancer can demonstrate prostatic infarcts (as enhancement defects) immediately post-PAE and monitor their resolution over time. The volume of prostatic infarcts can also be measured and compared to prostatic volume. Prostatic infarction is a definite sign of the local efficacy of PAE and a predictor of prostate shrinkage and (at least in some patients) of clinical success. CEUS can also be performed intraoperatively in the angio-suite, for on-site evaluation of the ischemic effect; a variation of this technique, with intraarterial (instead of intravenous) administration of diluted echo enhancer, can also be applied intraoperatively, to map the embolized territory and to prevent non-target embolization. Initial experience with US-elastographic techniques (shear-wave and strain elastography) has shown that they can detect and quantify the improvement of tissue elasticity post-PAE, thus providing new insights into the therapeutic mechanisms of this treatment. With utilization of high-end equipment, experience and standardized imaging protocols, US could be the primary modality for imaging evaluation of PAE.

Transarterial Chemoembolization of HCC with Radiopaque Microspheres: Evaluation with Computed Tomography and the Complementary Role of Contrast-Enhanced Ultrasonography.

PURPOSE: To assess the diagnostic performance of computed tomography (CT), and of the combination of CT with contrast-enhanced ultrasonography (CT + CEUS), for the early evaluation of local response of hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) with radiopaque drug-eluting microspheres (RO-DEMs). MATERIALS AND METHODS: 30 HCC patients (55 target tumors) were treated with TACE with RO-DEMs (diameter: 70-150 µm) preloaded with 75 mg doxorubicin/2 ml of microspheres. Unenhanced and contrast-enhanced CT, followed by CEUS, were performed 1-3 days post-RO-DEMs-TACE. Contrast-enhanced magnetic resonance (MR) performed 1 month later served as the reference standard. Local tumor response was evaluated with modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: MR diagnosed 9 tumors with complete response and 46 with residual disease. Compared to MR, CT had 9 false negative and 1 false positive diagnosis for residual tumor. Potential causes for these misdiagnoses were the hyperdensities and associated artifacts (caused by the accumulation of RO-DEMs in the target tumors) and the small size of residual tumor. CT + CEUS had 3 false negative and no false positive diagnosis for residual tumor. The sensitivity, specificity and diagnostic accuracy of CT for detection of residual tumor were, respectively: 80.4%, 88.9% and 81.8%, and for CT + CEUS: 93.5%, 100% and 94.5%, respectively. Agreement (kappa coefficient) in application of mRECIST between MR and CT was lower than between MR and CT + CEUS (0.508 vs. 0.757). CONCLUSION: CT evaluation of TACE with RO-DEMs is associated with limitations which can be partially overcome by combining CT with CEUS.

Prevalence, distribution and clinical significance of joints, muscles and bones in sarcoidosis: an 18F-FDG-PET/CT study.

OBJECTIVES: In Sarcoidosis joints-muscles-bones (JMBs) localizations are of the least common. 18F-FDG-PET/CT imaging revolutionized detection of JMBs involvement by adding metabolic activity information and allowing for a comprehensive, whole-body mapping of the disease. AIM AND METHODS: This study investigated prevalence, distribution, and clinical significance of JMBs sarcoidosis in 195 consecutive patients that underwent 18F-FDG PET/CT examination. RESULTS: Joint and bone involvement were encountered in 15% of patients with a mean of the maximum-standardized-uptake-value (SUVmax) of 6.1. Most common location was the axial skeleton. Hypercalciuria was significantly more frequent in patients with osseous involvement (p = 0.003). Muscle activity (SUVmax = 2.4) was encountered in 20% of the patients, most frequently in treatment-naïve (p = 0.02). The muscles of the lower extremities were affected the most. Muscle and bone localization coexist in 50% of the cases. JMBs disease was almost asymptomatic, not related to chronicity but to pulmonary, nodal, and systemic disease. Long-term follow-up and treatment response of affected patients confirmed sarcoidosis. CONCLUSION: 18F-FDG-PET/CT revealed JMBs localizations and coexistence with other organ sites supporting the concept that sarcoidosis is a systemic disease. By allowing an integrative interpretation of multi-organ involvement in the context of a pattern highly suggestive of sarcoidosis, it strongly keeps-off the diagnosis of malignancy.

Characteristics and Prognosis of Hepatocellular Carcinoma in Multi-Transfused Patients with ß-Thalassemia. Experience of a Single Tertiary Center.

BACKGROUND/AIM: The incidence of hepatocellular carcinoma (HCC) in patients with transfusion dependent thalassemia (TDT) has been increasing, where viral hepatitis and iron overload are the two established HCC risk factors. The aim of this study was to investigate the etiological factors of HCC development and to evaluate the possible factors associated with survival in our cohort of TDT patients with HCC. METHODS: Records of patients with TDT diagnosed with HCC from 2008 to 2018 were reviewed. Liver iron concentration (LIC) has been assessed by the signal-intensity-ratio MRI. The diagnosis of HCC was made by a 3-phase contrast magnetic resonance imaging (MRI) and patients were staged and treated for HCC according to Barcelona Clinic Liver Cancer (BCLC) grading system. RESULTS: Forty-two TDT patients with HCC have been included. Most of them (78.5%) were anti-HCV positive, 59.5% HCV-RNA positive, and 16.5% had serological markers of resolved HBV infection. Patients with HCV infection have been treated successfully with either Peg-IFNa±Ribavirin or with the new direct antivirals (DAAs). At the time of HCC diagnosis, all patients with chronic HCV infection were HCV-RNA negative, 78.5% had underlying cirrhosis, and the vast majority (98%) had average or mild elevated LIC values. According to the BCLC system, patients were classified as 0-A: 28.5%, B: 57% and C-D: 14.5%. HCC has been treated with loco-regional treatment in 78.5% of our patients, while the rest have received sorafenib. Twenty-eight patients (66.5%) died due to HCC with a median survival time of 6 months (range: 2-60). Using the Cox proportional hazard model, the only factors associated with poor survival were BCLC stages C and D. CONCLUSIONS: In conclusion, BCLC staging is the main prognostic factor of survival in patients with TDT who develop HCC.

Association of TIM-3 with BCLC Stage, Serum PD-L1 Detection, and Response to Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma.

Considering the increasing importance of immune checkpoints in tumor immunity we investigated the clinical relevance of serum T-cell immunoglobulin and mucin domain-3 (TIM-3) in patients with hepatocellular carcinoma (HCC). Serum TIM-3 levels were measured and their association with HCC stage and the detection of serum programmed death ligand-1 (PD-L1) were assessed. In patients submitted to transarterial chemoembolization (TACE), pre- and 1-week post-treatment TIM-3 levels were also evaluated. We studied 53 HCC patients with BCLC stages: 0 (5.7%), A (34%), B (32.1%), C (22.6%), and D (5.7%). The patients with advanced HCC (BCLC C) had significantly higher TIM-3 levels than patients with BCLC A (p = 0.009) and BCLC B (p = 0.019). TIM-3 levels were not associated with HCC etiology (p = 0.183). PD-L1 detection (9/53 patients) correlated with TIM-3 levels (univariate analysis, p = 0.047). In 33 patients who underwent TACE, post-treatment TIM-3 levels (231 pg/mL, 132-452) were significantly higher than pre-TACE levels (176 pg/mL, 110-379), (p = 0.036). Complete responders had higher post-TACE TIM-3 levels (534 pg/mL, 370-677) than partial responders (222 pg/mL, 131-368), (p = 0.028). Collectively, TIM-3 may have a role in anti-tumor immunity following TACE, setting a basis for combining immunotherapy and chemoembolization.

Role of locoregional therapies in the wake of systemic therapy.

Multiple systemic agents have recently been approved in the first- and second-line setting for hepatocellular carcinoma (HCC), increasing the therapeutic options for patients and treating physicians. The randomised controlled trials that led to these approvals were predominantly conducted in a population comprised of patients with advanced HCC. However, these trials also included a subset of patients who had progressed after locoregional therapies (LRTs), mostly transarterial chemoembolisation. With a greater number of systemic agents available, the role of LRTs has become a topic of debate, specifically regarding when to transition to systemic therapy in unresectable HCC and the potential opportunities for combining locoregional and systemic therapies. Trials of immuno-oncology agents (notably T cell checkpoint inhibitors) are ongoing in the advanced disease setting and these agents also present opportunities for combination therapies, both with other systemic agents and with LRTs in earlier stage disease. This article will review strategies to guide patient selection for LRT as well as the development of locoregional-systemic combinations based on scientific rationale and the challenges of clinical trial design in this setting.

18F-FDG PET/CT in Pulmonary Sarcoidosis:Quantifying Inflammation by the TLG index.

Objectives: In sarcoidosis progressive pulmonary disease affects prognosis. Pulmonary disease activity estimated by classic means poorly predicts severity and progressiveness. 18F-fluoro-2-deoxyglucose-positron-emission-tomography computed-tomography (18F-FDG-PET/CT) estimates pulmonary activity by inflammatory-cells metabolism. We aimed to investigate pulmonary sarcoidosis by 18F-FDG-PET/CT and evaluate the role of total-lesion-glycolysis (TLG) value, as an index quantifying the whole burden of lung inflammation.Methods: This is a retrospective study of sequentially gathered data. From a Greek cohort of 195 sarcoidosis-patients, 87 were identified with lung increased 18F-FDG uptake and further studied.Results: Visualizing lung by 18F-FDG-PET/CT identified new imaging patterns and revealed activity in all Scadding stages. Ever-smokers presented significantly higher TLG and lower DLCO compared to never-smokers. However, TLG value did not correlate with functional indices and did not differ between symptomatic and non-symptomatic patients. Among treatment-naïve patients, TLG did not differ significantly in those requiring therapy compared to those remained off.Conclusion: 18F-FDG PET/CT improved imaging and detection of pulmonary involvement and through TLG value revealed the deleterious smoking effect. The fact that TLG neither detected patients with clinical symptoms and functional impairment nor identified those requiring treatment once again confirms that in pulmonary sarcoidosis the link between activity, severity and decision to treat still eludes us.