Whole-body low-dose computed tomography (WBLDCT) in staging and re-staging of multiple myeloma.

The objective of this study is to evaluate the prognostic features of multiple myeloma (MM) using whole-body low-dose computed tomography (WBLDCT). One hundred three patients with biopsy-proven MM who underwent WBLDCT were retrospectively enrolled. The evolution of osteolytic lesions overtime was performed by measuring the maximum axial diameter at the baseline (T0) and the end of follow-up (Te), by using a cut-off value of 10 mm. The location and dimension of up to three lesions were registered. The time-to-fracture (TTF) was recorded. Sixty-three percent of patients presented a focal pattern, 22% a diffuse pattern, and 15% a combined one. Seventy-two percent of patients with lesions ≤ 10 mm presented stability, 27% a dimensional increase, and 1% a decrease. Patients with lesions >10 mm showed a statistically significant difference regarding the mean difference of axial diameter between T0 and Te (p = 0.015). Patients with lesions >10 mm showed an odds ratio (OR) of 29.8 (95%CIs 3.8-230.5) to develop at least one fracture. Mean TTF was significantly lower in patients with lesions >10 mm in comparison with lesions ≤ 10 mm (9 ± 3 vs 23 ± 7 months, respectively, p = 0.011). WBLDCT represents a reliable imaging-based tool for proper management of MM patients, showing that diffuse form or small lytic lesions may deserve a less frequent follow-up.

Computed tomography semi-automated lung volume quantification in SARS-CoV-2-related pneumonia.

OBJECTIVES: To evaluate a semi-automated segmentation and ventilated lung quantification on chest computed tomography (CT) to assess lung involvement in patients affected by SARS-CoV-2. Results were compared with clinical and functional parameters and outcomes. METHODS: All images underwent quantitative analyses with a dedicated workstation using a semi-automatic lung segmentation software to compute ventilated lung volume (VLV), Ground-glass opacity (GGO) volume (GGO-V), and consolidation volume (CONS-V) as absolute volume and as a percentage of total lung volume (TLV). The ratio between CONS-V, GGO-V, and VLV (CONS-V/VLV and GGO-V/VLV, respectively), TLV (CONS-V/TLV, GGO-V/TLV, and GGO-V + CONS-V/TLV respectively), and the ratio between VLV and TLV (VLV/TLV) were calculated. RESULTS: A total of 108 patients were enrolled. GGO-V/TLV significantly correlated with WBC (r = 0.369), neutrophils (r = 0.446), platelets (r = 0.182), CRP (r = 0.190), PaCO2 (r = 0.176), HCO3- (r = 0.284), and PaO2/FiO2 (P/F) values (r = - 0.344). CONS-V/TLV significantly correlated with WBC (r = 0.294), neutrophils (r = 0.300), lymphocytes (r = -0.225), CRP (r = 0.306), PaCO2 (r = 0.227), pH (r = 0.162), HCO3- (r = 0.394), and P/F (r = - 0.419) values. Statistically significant differences between CONS-V, GGO-V, GGO-V/TLV, CONS-V/TLV, GGO-V/VLV, CONS-V/VLV, GGO-V + CONS-V/TLV, VLV/TLV, CT score, and invasive ventilation by ET were found (all p < 0.05). CONCLUSION: The use of quantitative semi-automated algorithm for lung CT elaboration effectively correlates the severity of SARS-CoV-2-related pneumonia with laboratory parameters and the need for invasive ventilation. KEY POINTS: • Pathological lung volumes, expressed both as GGO-V and as CONS-V, can be considered a useful tool in SARS-CoV-2-related pneumonia. • All lung volumes, expressed themselves and as ratio with TLV and VLV, correlate with laboratory data, in particular C-reactive protein and white blood cell count. • All lung volumes correlate with patient's outcome, in particular concerning invasive ventilation.

Influence of injection rate in determining the development of artifacts during the acquisition of dynamic arterial phase in Gd-EOB-DTPA MRI studies.

OBJECTIVE: To assess whether different Gd-EOB-DTPA injection rates could influence the development of artifacts during the arterial phase of liver MRI studies. MATERIALS AND METHODS: All Gd-EOB-DTPA liver MRI studies performed for different clinical indications at a single tertiary referral center were retrospectively evaluated. Each examination was acquired on a 1.5 T scanner with T1 In- and Out-of-Phase, T2 with and without fat-saturation, DWI, and 3D-T1 fat-sat dynamic sequences. Patients were divided into two groups according to the injection rate (1 ml/s and 1.5 ml/s). A single radiologist recorded the presence or absence of artifacts during different acquisition phases, respectively: (1) all examination; (2) only during the arterial phase; (3) only during the portal-venous phase; (4) both in arterial and portal-venous phases. From a total of 748 MRI studies performed, 229 were excluded due to the presence of artifacts during the entire examination. The remaining 519 MRI studies were divided into two groups according to the injection rate. RESULTS: The first group (flow rate = 1 ml/s) was composed by 312 (60.1%) patients and the second group (flow rate = 1.5 ml/s) by 207 (39.9%) patients. In the first group, 2 (0.6%) patients showed artifacts in all dynamic sequences; 13 (4%) only in the arterial phase, 16 (5%) only in the portal-venous phase, and 38 (12%) both in arterial and portal-venous phases; a total of 243 (78%) showed no artifacts. In the second group, 3 (1.5%) patients had artifacts in all dynamic sequences, 82 (40%) only in the arterial phase, 20 (10%) only in the portal-venous phase, and 53 (25%) both in arterial and portal-venous phases; a total of 49 (23.5%) showed no artifacts. A significant difference between the two groups regarding the absence of artifacts in all examination and the presence of artifacts only during the arterial phase was found (p < 0.001). CONCLUSION: The development of artifacts during the arterial phase of Gd-EOB-DTPA liver MRI studies could be related to the injection rate and its reduction may help to decrease the incidence of artifacts.

Acute pulmonary embolism in hospitalized patients with SARS-CoV-2-related pneumonia: multicentric experience from Italian endemic area.

PURPOSE: To analyze pulmonary embolism (PE) on chest computed tomography pulmonary angiography (CTPA) in hospitalized patients affected by SARS-CoV-2, according to the severity of lung disease based both on temporal CT features changes and on CT-severity lung involvement (CT-severity score), along with the support of clinical and laboratory findings. METHODS: We retrospectively enrolled a total of 170 patients with confirmed SARS-CoV-2 infection who underwent CTPA examination for PE suspicion. Pulmonary arteries diameters, right ventricle/left ventricle (RV/LV) ratio, presence, absence, and distribution of PE, pulmonary artery obstructive index (PAO index), and lobe involvement were recorded. All CT scans were reviewed to assess temporal CT changes and the COVID CT-severity score. RESULTS: A total of 76 out of 170 patients (44.7%) developed PE without having any major risk factors for venous thromboembolism. The most severe pulmonary arteries involvement, expressed in terms of PAO Index, occurred in those patients with markedly elevated D-dimer and C-reactive protein (CRP) values and those patients with an advanced temporal stage of lung disease. The majority PE-positive patients were hospitalized in non-intensive wards. PE-positive patients showed a slightly higher hospitalization time in comparison with PE-negative ones. In the three months of study, overall 85.9% of patients were discharged while 14.1% died, of whom 13 PE-positive (54.2%). CONCLUSIONS: Patients hospitalized for SARS-CoV-2 infection present a higher cumulative incidence of PE compared to the general population of hospitalized patients, regardless of the severity of lung inflammation or the temporal stage of the disease.

Diagnostic accuracy of multiparametric magnetic resonance imaging combined with clinical parameters in the detection of clinically significant prostate cancer: A novel diagnostic model.

OBJECTIVES: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging in the detection of prostate cancer, according to Prostate Imaging Reporting and Data System, and the usefulness of combining clinical parameters to improve patients' risk assessment. METHODS: Overall, 201 patients underwent multiparametric magnetic resonance imaging investigation with a 3-T magnet and a 32-channel body coil based on triplanar high-resolution T2-weighted, diffusion-weighted and T1-weighted dynamic contrast-enhanced imaging before, during and after intravenous administration of paramagnetic contrast agent. Random transrectal ultrasound-guided biopsy was carried out for all eligible patients. If a Prostate Imaging Reporting and Data System ≥3 lesion was present, a targeted biopsy with magnetic resonance imaging-transrectal ultrasound fusion-guided system was carried out. RESULTS: Sensitivity, specificity, positive predictive value and negative predictive value of Prostate Imaging Reporting and Data System ≥3 lesions for the detection of prostate cancer were 65.1%, 54.9%, 43.1% and 75.0% respectively, with an accuracy of 64.2% (55.1-72.7%). At uni- and multivariate analysis, age ≥70 years and prostate-specific antigen density ≥0.15 ng/mL/mL were significantly associated with prostate cancer. A new risk model named "modified Prostate Imaging Reporting and Data System" was created considering age and prostate-specific antigen density in addition to the Prostate Imaging Reporting and Data System score showing an improved correlation with prostate cancer compared with the Prostate Imaging Reporting and Data System alone (area under curve 71.4%, 95% confidence interval 62.2-80.5 vs area under curve 62.6%, 95% confidence interval 52.1-73; P ≤ 0.0001). CONCLUSIONS: The accuracy of Prostate Imaging Reporting and Data System alone in the diagnosis of prostate cancer might be suboptimal, whereas a novel risk model based on the combination of multiparametric magnetic resonance imaging data with clinical parameters could offer higher discrimination and improve the ability of diagnosing clinically significant disease.

Diagnostic Value of Quantitative Perfusion Computed Tomography Technique in the Assessment of Tumor Response to Sorafenib in Patients With Advanced Hepatocellular Carcinoma.

AIM: The aim of this study was to assess the role of dynamic contrast-enhanced perfusion computed tomography (pCT) imaging in the early detection of blood flow changes related to antiangiogenic treatment with sorafenib, in patients with advanced hepatocellular carcinoma (HCC), being the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria the standard of reference. METHODS: Between 2012 and 2016, 43 cirrhotic patients (male, n = 39; female, n = 4) with biopsy-proven multifocal HCC underwent multi-detector-row computed tomography, and pCT examinations were performed before and every 2 months after sorafenib administration. Perfusion CT technique is based on the acquisition of 16 dynamic slices/scan per 40 scans, performed on a 256-slice multi-detector-row computed tomography scanner, after intravenous bolus injection of 50 mL of iodinated contrast agent (350 mg I/mL) at a flow rate of 5 mL/s. According to mRECIST, patients were stratified into complete (CR) or partial response (PR) and stable (SD) or progressive disease (PD). The following pCT parameters were calculated: hepatic perfusion (mL/s per 100 g), time to peak (seconds), arterial perfusion (mL/s), and hepatic perfusion index (%). Perfusion CT values at baseline and first follow-up were reported for all mRECIST groups and then compared between the nonprogressor (CR, PR, SD) and progressor groups (PD). RESULTS: Most pCT values were significantly higher (P < 0.01) between baseline and follow-up in the CR and PR groups, whereas nonsignificant differences were found among SD patients, and a nonsignificant trend (P > 0.05) toward increase was observed among PD patients. Moreover, pCT values were significantly higher (P = 0.05) at baseline in the nonprogressor group compared with the progressor. CONCLUSION: Preliminary results suggest that pCT adds quantitative data of vascularization, thus demonstrating its usefulness in the assessment of therapeutic response to sorafenib in advanced HCC, in line with mRECIST criteria, offering 1-step information on tissue cellularity and vascularization.

Evaluation of image quality and radiation dose saving comparing knowledge model-based iterative reconstruction on 80-kV CT pulmonary angiography (CTPA) with hybrid iterative reconstruction on 100-kV CT.

OBJECTIVES: To evaluate dose reduction and image quality of 80-kV CT pulmonary angiography (CTPA) reconstructed with knowledge model-based iterative reconstruction (IMR), and compared with 100-kV CTPA with hybrid iterative reconstruction (iDose4). MATERIALS AND METHODS: One hundred and fifty-one patients were prospectively investigated for pulmonary embolism; a study group of 76 patients underwent low-kV setting (80 kV, automated mAs) CTPA study, while a control group of 75 patients underwent standard CTPA protocol (100 kV; automated mAs); all patients were examined on 256 MDCT scanner (Philips iCTelite). Study group images were reconstructed using IMR while the control group ones with iDose4. CTDIvol, DLP, and ED were evaluated. Region of interests placed in the main pulmonary vessels evaluated vascular enhancement (HU); signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. RESULTS: Compared to iDose4-CTPA, low-kV IMR-CTPA presented lower CTDIvol (6.41 ± 0.84 vs 9.68 ± 3.5 mGy) and DLP (248.24 ± 3.2 vs 352.4 ± 3.59 mGy × cm), with ED of 3.48 ± 1.2 vs 4.93 ± 1.8 mSv. Moreover, IMR-CTPA showed higher values of attenuation (670.91 ± 9.09 HU vs 292.61 ± 15.5 HU) and a significantly higher SNR (p < 0.0001) and CNR (p < 0.0001).The subjective image quality of low-kV IMR-CTPA was also higher compared with iDose4-CTPA (p < 0.0001). CONCLUSIONS: Low-dose CTPA (80 kV and automated mAs modulation) reconstructed with IMR represents a feasible protocol for the diagnosis of pulmonary embolism in the emergency setting, achieving high image quality with low noise, and a significant dose reduction within adequate reconstruction times(≤ 120 s).

Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) CONCLUSIONS: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment.

Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma.

BACKGROUND & AIMS: The Barcelona Clinic Liver Cancer intermediate stage (BCLC-B) of hepatocellular carcinoma (HCC) includes extremely heterogeneous patients in terms of tumour burden and liver function. Transarterial-chemoembolization (TACE) is the first-line treatment for these patients although it may be risky/useless for someone, while others could undergo curative treatments. This study assesses the treatment type performed in a large cohort of BCLC-B patients and its outcome. METHODS: Retrospective analysis of 485 consecutive BCLC-B patients from the ITA.LI.CA database diagnosed with naïve HCC after 1999. Patients were stratified by treatment. RESULTS: 29 patients (6%) were lost to follow-up before receiving treatment. Treatment distribution was: TACE (233, 51.1%), curative treatments (145 patients, 31.8%), sorafenib (18, 3.9%), other (39, 8.5%), best supportive care (BSC) (21, 4.6%). Median survival (95% CI) was 45 months (37.4-52.7) for curative treatments, 30 (24.7-35.3) for TACE, 14 (10.5-17.5) for sorafenib, 14 (5.2-22.7) for other treatments and 10 (6.0-14.2) for BSC (P<.0001). Independent prognosticators were gender and treatment. Curative treatments reduced mortality (HR 0.197, 95%CI: 0.098-0.395) more than TACE (HR 0.408, 95%CI: 0.211-0.789) (P<.0001) as compared with BSC. Propensity score matching confirmed the superiority of curative therapies over TACE. CONCLUSIONS: In everyday practice TACE represents the first-line therapy in an half of patients with naïve BCLC-B HCC since treatment choice is driven not only by liver function and nodule characteristics, but also by contraindications to procedures, comorbidities, age and patient opinion. The treatment type is an independent prognostic factor in BCLC-B patients and curative options offer the best outcome.

The evolutionary scenario of hepatocellular carcinoma in Italy: an update.

BACKGROUND & AIMS: Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of aetiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. METHODS: Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centres from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). RESULTS: The main results were as follows: (i) progressive patient aging; (ii) progressive expansion of non-viral cases and, namely, of "metabolic" hepatocellular carcinomas; (iii) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semi-annual) surveillance programme; (iv) favourable cancer stage migration; (v) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early- or intermediate-stage hepatocellular carcinoma. CONCLUSIONS: During the last 15 years several aetiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was owing both to the wider use of semi-annual surveillance, expanding the proportion of tumours that qualified for curative treatments, and to the improved outcome of loco-regional treatments.

Prognosis of untreated hepatocellular carcinoma.

UNLABELLED: The prognosis of untreated patients with hepatocellular carcinoma (HCC) is heterogeneous, and survival data were mainly obtained from control arms of randomized studies. Clinical practice data on this topic are urgently needed, so as to help plan studies and counsel patients. We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group. Prognosis was evaluated by subdividing patients according to the Barcelona Clinic Liver Cancer (BCLC) classification. We also assessed the main demographic, clinical, and oncological determinants of survival in the subgroup of patients with advanced HCC (BCLC C). Advanced (BCLC C: n = 138; 23.0%) and end-stage HCC (BCLC D; n = 210; 35.0%) represented the majority of patients. Overall median survival was 9 months, and the principal cause of death was tumor progression (n = 279; 46.5%). Patients' median survival progressively and significantly decreased as BCLC stage worsened (BCLC 0: 38 months; BCLC A: 25 months; BCLC B: 10 months; BCLC C: 7 months; BCLC D: 6 months; P < 0.0001). Female gender (hazard ratio [HR] = 0.55; 95% confidence interval [CI] = 0.33-0.90; P = 0.018), ascites (HR = 1.81; 95% CI = 1.21-2.71; P = 0.004), and multinodular (>3) HCC (HR = 1.79; 95% CI = 1.21-2.63; P = 0.003) were independent predictors of survival in patients with advanced HCC (BCLC C). CONCLUSION: BCLC adequately predicts the prognosis of untreated HCC patients. In untreated patients with advanced HCC, female gender, clinical decompensation of cirrhosis, and multinodular tumor are independent prognostic predictors and should be taken into account for patient stratification in future therapeutic studies.

Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: implications for its clinical use.

BACKGROUND: α-Fetoprotein (AFP) is a biomarker commonly used in the management of patients with hepatocellular carcinoma (HCC), although the possible determinants of its serum levels in these patients have not been adequately explored. For this study, the authors evaluated the relevance of demographic, clinical, and oncologic factors to the presence of elevated AFP levels in large cohort of patients with HCC. METHODS: In 4123 patients with HCC who were managed by the Italian Liver Cancer Group, AFP levels were assessed along with their association with demographic, biochemical, clinical, and oncologic characteristics. Patients were subdivided according to the presence of elevated AFP (ie, >10 ng/mL). RESULTS: AFP levels were elevated in 62.4% of patients with HCC. Multivariate logistic regression analysis indicated that being a woman (odds ratio [OR], 1.497; 95% confidence interval [95%CI], 1.250-1.793; P < .0001), the presence of cirrhosis (OR, 1.538; 95% CI, 1.050-2.254; P = .027), liver disease with viral etiology (OR, 1.900; 95% CI, 1.589-2.272; P < .0001), an elevated alanine aminotransferase level (OR, 1.878; 95% CI, 1.602-2.202; P < .0001), a low albumin level (OR, 1.301; 95% CI, 1.110-1.525; P = .012), an HCC tumor size >2 cm (OR, 1.346; 95% CI, 1.135-2.596; P = .001), multinodular HCC (OR, 1.641; 95% CI, 1.403-1.920; P < .0001), and the presence of vascular invasion (OR, 1.774; 95% CI, 1.361-2.311; P < .0001) were associated independently with elevated levels of AFP. Both the median AFP level and the proportion of patients who had elevated levels increased with decreasing degrees of HCC differentiation (P < .0001). CONCLUSIONS: Sex and features of chronic liver disease were identified as nontumor characteristics that influence serum AFP levels in patients with HCC. These findings should be taken into account as limitations in interpreting the oncologic meaning of this biomarker in clinical practice.

Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma.

BACKGROUND & AIMS: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. METHODS: One-thousand three-hundred and eighty Child-Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. RESULTS: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p<0.001). In a 10-year follow-up perspective, the median lead-time calculated for all surveilled patients was 6.5 months (7.2 for semiannual and 4.1 for annual surveillance). Lead-time bias accounted for most of the surveillance benefit until the third year of follow-up after HCC diagnosis. However, even after lead-time adjustment, semiannual surveillance maintained a survival benefit over symptomatic diagnosis (number of patients needed to screen = 13), as did annual surveillance (18 patients). CONCLUSIONS: Lead-time bias is the main determinant of the short-term benefit provided by surveillance for HCC, but this benefit becomes factual in a long-term perspective, confirming the clinical utility of an anticipated diagnosis of HCC.

Evaluation of the impact of transient interruption of antiangiogenic treatment using ultrasound-based techniques in a murine model of hepatocellular carcinoma.

BACKGROUND: Development of escape pathways from antiangiogenic treatments was reported to be associated with enhanced tumor aggressiveness and rebound effect was suggested after treatment stop. Aim of the study was to evaluate tumor response simulating different conditions of administration of antiangiogenic treatment (transient or definitive treatment stop) in a mouse model of hepatocellular carcinoma. METHODS: Subcutaneous tumors were created by inoculating 5 × 10(6) Huh7 cells into the right flank of 14 nude mice. When tumor size reached 5-10 mm, mice were divided in 3 groups: group 1 was treated with placebo, group 2 was treated with sorafenib (62 mg/kg via gavage) but temporarily suspended from day +5 to +9, whereas in group 3 sorafenib was definitively stopped at day +5. At day +13 all mice were sacrificed, collecting masses for Western-Blot analyses. Volume was calculated with B-mode ultrasonography at day 0, +5, +9, +11 and +13. VEGFR2-targeted contrast-enhanced ultrasound using BR55 (Bracco Imaging) was performed at day +5 and +13 and elastonosography (Esaote) at day +9 and +11 to assess tumor stiffness. RESULTS: Median growth percentage delta at day +13 versus day 0 was 197% (115-329) in group 1, 81% (48-144) in group 2 and 111% (27-167) in group 3. Median growth delta at day +13 with respect to day +5 was 79% (48-127), 37% (-14128) and 81% (15-87) in groups 1, 2 and 3, respectively. Quantification of targeted-CEUS at day +13 showed higher values in group 3 (509 Arbitrary Units AI, range 293-652) than group 1 (275 AI, range 191-494) and group 2 (181 AI, range 63-318) (p=0.033). Western-Blot analysis demonstrated higher VEGFR2 expression in group 3 with respect to group 1 and 2. CONCLUSIONS: A transient interruption of antiangiogenic treatment does not impede restoration of tumor response, while a definitive interruption tends to stimulate a rebound of angiogenesis to higher level than without treatment.

Multidisciplinary treatment of hepatocellular carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part II - Non-surgical treatments.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of its management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the second part of guidelines, focused on the multidisciplinary tumor board of experts and non-surgical treatments of HCC.

Multidisciplinary Treatment of Hepatocellular Carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part I - Surgical treatments.

Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.

Rise and fall of HCV-related hepatocellular carcinoma in Italy: a long-term survey from the ITA.LI.CA centres.

BACKGROUND & AIMS: Hepatitis C virus (HCV) is the leading aetiological factor of HCC in the western world where, overall, its incidence is increasing, despite data suggesting an initial drop in some areas. The aim of this study was to evaluate epidemiology, clinical features and survival of HCV-related HCC (HCV-HCC) in a wide time range in Italy. METHODS: Multicentre retrospective study including 3695 patients prospectively recruited by the ITA.LI.CA group. Patients were classified into three subgroups according to aetiology (Group A[GA], pure HCV; Group B[GB], HCV + cofactors; and Group C[GC], non-HCV) and in 5 time cohorts (5 years each), according to the year of diagnosis. Age, gender, Child-Pugh score, modality of diagnosis, stage, presence of thrombosis/metastases, type of treatment and survival were analysed. RESULTS: A total of 1801 GA patients, 445 GB and 1333 GC were recruited. The number of GA patients peaked in the 1996-2000, gradually dropping thereafter (P < 0.0001), as observed for GB (P < 0.0001). Age at diagnosis increased (P < 0.0001), while percentage of patients diagnosed during surveillance and stage improved only in GA (P = 0.02 and P = 0.003 respectively). The survival significantly increased over time particularly in GA (median 37 months) and was longer in GA than in GB and GC (P < 0.0001). CONCLUSIONS: The prevalence of HCC-HCV is decreasing in Italy since 2001. HCV-HCC patients are older, more frequently diagnosed under surveillance and in an earlier stage. HCC survival improved in the last 15 years and is significantly higher in patients with HCV-HCC. We therefore expect a further drop in both incidence and mortality for HCV-HCC in the years to come.

Synchronous hepatocellular carcinoma and renal cell carcinoma in young woman with sarcoidosis: A case report.

Hepatocellular carcinoma (HCC) and clear cell renal carcinoma are both frequent cancers, especially in patients with risk factors such as cirrhosis in the first case or genetic mutations such as Li-Fraumeni syndrome in the second case; however, their synchronous appearance is very rare especially in young patients with no apparent predisposing factors. We describe the case of a 33-year-old woman with acute pain onset in right hypochondrium. The ultrasound (US) imaging and the contrast-enhanced computed tomography (CECT) of the abdomen revealed 2 abdominal masses: one in the VI-VII segments of the liver and the other one in the right kidney. The chest CECT study, acquired for staging purpose, detected multiple micronodules with patchy peri-bronchial distribution at both lungs. At the histological examination, the tumor arising from the right kidney was finally diagnosed as clear cell renal carcinoma, whereas the tumor arising from the right lateral hepatic lobe as HCC. The histological examination of lung lesions revealed sarcoidosis granulomas. The patient is still being followed up for the occurrence of lung and lymph node metastases from HCC 14 months later.