•Not all tumor nodules are clearly detectable in conventional B-mode US.•Localization and targeting of small HCC nodules and metastases with inadeguate ultrasound may decrease ablation ...effectiveness.•Contrast enhanced ultrasound can be used to guide percutanepus ablation in the case of undetectable or poorly visible targets.•This study represents a snapshot of the use of CEUS-guided ablation in real practice of Interventional Ultrasound Centers.
The present retrospective study was aimed at characterizing the clinical impact of contrast-enhanced ultrasound (CEUS) as a guidance technique for ablation of primary and secondary liver tumors at six interventional ultrasound centers. 148 patients (103M/45F, median age 74 yrs.) with 151 liver target lesions (median size 15 mm, 86.7% Hepatocellular Carcinomas) in whom CEUS guidance was used for Percutaneous Ethanol Injection (35.2%), Radiofrequency (46.3%) and Microwave (18.5%) were selected during the period 2008–2016. CEUS-guided ablations represented 7.3% (range 2.5%–13.8%) of 2015 ablative sessions performed at the participating centers. Indications to CEUS-guided ablation were: improvement of conspicuity of the target (28.5%), a target lesion undetectable on B-mode ultrasound (29.8%), detection of viable areas in nodules with either incomplete ablation or local tumor progression (41.7%). Overall, complete radiological ablation was obtained in 113/151 tumors (74.8%), with heat-based techniques (RF and MW) achieving higher rate of successful ablation (86.7%) than PEI (51%). Neither deaths nor major complications occurred after ablations.
CEUS guidance demonstrates improved visibility and effectiveness in aiding ablation procedures that are otherwise technically difficult using only B-Mode US guidance.
Background and aims
Epidemiology of hepatocellular carcinoma (HCC) is changing in most areas of the world. This study aimed at updating the changing scenario of aetiology, clinical presentation, ...management and prognosis of HCC in Italy during the last 15 years.
Methods
Retrospective analysis of the Italian Liver Cancer (ITA.LI.CA) database included 6034 HCC patients managed in 23 centres from 2004 to 2018. Patients were divided into three groups according to the date of cancer diagnosis (2004‐2008, 2009‐2013 and 2014‐2018).
Results
The main results were: (i) a progressive patient ageing; (ii) a progressive increase of non‐viral cases and, particularly, of ‘metabolic’ and ‘metabolic + alcohol’ HCCs; (iii) a slightly decline of cases diagnosed under surveillance, but with an incremental use of the semiannual schedule; (iv) a favourable cancer stage migration; (v) an increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) an improved overall survival (adjusted for the lead time in surveyed patients) in the last calendar period, particularly in viral patients; (viii) a large gap between the number of potential candidates (according to oncologic criteria and age) to liver transplant and that of transplanted patients.
Conclusions
During the last 15 years several aspects of HCC scenario have changed, as well as its management. The improvement in patient survival observed in the last period was likely because of a larger use of thermal ablation with respect to the less effective alcohol injection and to an improved management of intermediate stage patients.
Transrectal ultrasound can reveal potentially malignant prostate lesions while they are still small. However, based on ultrasound alone they are often difficult to distinguish from benign focal ...lesions. We tested the reliability of a new technique for the sonographic evaluation of typical prostate lesions in differentiating adenocarcinoma from benign lesions.
During 18 months 398 consecutive male patients 45 to 76 years old underwent transrectal ultrasound for the early detection of prostate cancer. When suspicious hypoechoic lesions were noted in the peripheral regions of the prostate, moderate pressure was applied on the lesion using the ultrasound probe to evaluate consistency. Based on the response lesions were classified as deformable (the shape changed from approximately spherical to oval) or nondeformable (the original shape was retained). All lesions were then diagnosed based on fine needle biopsy.
Peripheral hypoechoic prostate lesions were sonographically identified in 146 of 398 patients (36.7%). In 68 cases nondeformable lesions proved to be adenocarcinoma in 63 (92.6%), and chronic prostatitis and/or adenomatous hyperplasia in 5. In contrast, 62 of the 78 deformable nodules (79.5%) showed histological features of hyperplasia and/or chronic inflammation. The remaining 16 nodules, which showed more limited changes in shape during compression, were characterized by hyperplasia with acute inflammatory changes. In 5 cases there was also evidence of adenocarcinoma.
Ultrasound guided compression of suspicious prostate lesions detected on transrectal sonography is a simple, rapid and reliable maneuver that may increase the diagnostic potential of this examination.
Background & Aims The role of hepatic resection for hepatocellular carcinoma (HCC) in different Barcelona Clinic Liver Cancer (BCLC) stages is controversial. We aimed at measuring the survival ...benefit of resection vs. non-surgical-therapies in each BCLC stage. Methods Using the ITA.LI.CA database, we identified 2090 BCLC A, B, and C HCC patients observed between 2000 and 2012: 550 underwent resection, 1046 loco-regional therapy (LRT), and 494 best supportive care (BSC). A multivariate log-logistic model was chosen to predict median survival (MS) after resection vs. MS after LRT or BSC. The results were expressed as net survival benefit of resection: (MS resection – MS LRT)/MS BSC. Results After stratifying for BCLC stage, the median net survival benefit of resection over LRT was: BCLC 0 = 62% (40%, 82%), A = 45% (13%, 65%), B = 46% (9%, 76%), C = −16% (−55%, 33%). Model for end-stage liver disease (MELD) score >9, Child B class, and performance status (PST) = 2 were the main risk factors for liver resection. 1181 Child A patients (57%) with MELD ⩽9 and PST <2 had always a large positive net survival benefit of resection over LRT, independently of BCLC stage: BCLC 0 = 64% (44%, 85%), A = 59% (45%, 74%), B = 71% (52%, 90%), C = 56% (36%, 78%). Among the 909 (43%) patients with at least one risk factor (MELD >9 or PST = 2 or Child B class), resection did not prove any survival benefit over LRT. Conclusions Resection could result in survival benefit over LRT for HCC patients regardless of their BCLC stage, provided that liver dysfunction (Child B or MELD >9) and PST >1 are absent.
Background & Aims The current guidelines recommend the surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on liver ultrasonography repetition at either 6 ...or 12 month intervals, since there is no compelling evidence of superiority of the more stringent program. This study aimed at comparing cancer stage, treatment applicability, and survival between patients on semiannual or annual surveillance. Methods We analyzed the clinical records of 649 HCC patients in Child-Pugh class A or B, observed in ITA.LI.CA centers. HCC was detected in 510 patients submitted to semiannual surveillance (Group 1) and in 139 submitted to annual surveillance (Group 2). In Group 1 the survival was presented as observed and corrected for the lead time. Results The cancer stage was less severe in Group 1 than in Group 2 ( p < 0.001), with more single tiny (⩽2 cm) and less advanced tumors. Treatment applicability was improved by the semiannual program ( p = 0.020). The median observed survival was 45 months (95% CI 40.0–50.0) in Group 1 and 30 months (95% CI 24.0–36.0) in Group 2 ( p = 0.001). The median corrected survival of Group 1 was 40.3 months (95% CI 34.9–45.7) ( p = 0.028 with respect to the observed survival of Group 2). Age, platelet count, α-fetoprotein, Child-Pugh class, cancer stage, and hepatocellular carcinoma treatment were independent prognostic factors. Conclusions Semiannual surveillance increases the detection rate of very early hepatocellular carcinomas and reduces the number of advanced tumors as compared to the annual program. This translates into a greater applicability of effective treatments and into a better prognosis.
The presence of cirrhosis is the only risk factor that is advocated for recurrence of hepatocellular carcinoma (HCC) 2 years after hepatic resection compared with noncirrhotic control subjects; ...however, data for cohorts of exclusively patients with cirrhosis are lacking. This study was designed to assess risk factors and annual incidence of early (<2 years) and late (>2 years) recurrence after resection of cirrhosis and to compare these findings with those of patients with cirrhosis enrolled in HCC surveillance programs (HCC occurrence). Data from 204 patients with cirrhosis resected for HCC and 150 surveilled for cirrhosis were retrospectively collected and compared using propensity score matching to overcome biases of nonrandomized study. Risk factors for early recurrence (incidence = 21.8%/year) were higher serum alpha-fetoprotein (AFP) levels, poorly differentiated tumor, and presence of microvascular invasion (
P
< 0.05). Risk factors for both late recurrence (18.4%/year) and HCC occurrence (3.3%/year) were male gender, older age, and higher serum transaminase levels; multiple primary tumors and higher AFP were additional risk factors for late recurrence and HCC occurrence respectively (
P
< 0.05). After propensity adjustment, resected patients with less than two risk factors for late recurrence showed an annual incidence of HCC (6.2%/year) similar to that of surveilled patients with ≥2 risk factors (5.8%/year;
P
= 0.898). Early and late recurrence of HCC for patients with cirrhosis after resection have distinct risk factors. Annual incidence of HCC 2 years or more after resection may be similar to that of general patients because the same risk factors are involved; assessment of these characteristics could be useful in tailoring clinical management.
The Barcelona Clinic Liver Cancer (BCLC) intermediate stage (BCLC B) includes a heterogeneous population of patients with hepatocellular carcinoma (HCC). Recently, in order to facilitate treatment ...decisions, a panel of experts proposed to subclassify BCLC B patients. In this study, we aimed to assess the prognostic capability of the BCLC B stage reclassification in a large cohort of patients with untreated HCC managed by the Italian Liver Cancer Group.
We assessed the prognosis of 269 untreated HCC patients observed in the period 1987-2012 who were reclassified according to the proposed subclassification of the BCLC B stage from stage B1 to stage B4. We evaluated and compared the survival of the various substages.
Median survival progressively decreased from stage B1 (n=65, 24.2%: 25 months) through stages B2 (n=105, 39.0%: 16 months) and B3 (n=22, 8.2%: 9 months), to stage B4 (n=77, 28.6%: 5 months; P<0.0001). Moreover, we observed a significantly different survival between contiguous stages (B1 vs. B2, P=0.0002; B2 vs. B3, P<0.0001; B3 vs. B4, P=0.0219). In multivariate analysis, the BCLC B subclassification (P<0.0001), MELD score (P=0.0013), and platelet count (P=0.0252) were independent predictors of survival.
The subclassification of the intermediate-stage HCC predicts the prognosis of patients with untreated HCC. The prognostic figures identified in this study may be used as a benchmark to assess the efficacy of therapeutic intervention in the various BCLC B substages, whereas it remains to be established whether incorporation of the MELD score might improve the prognosis of treated patients.
Conflicting evidence indicates that HIV seropositivity may influence the outcome of patients with hepatocellular carcinoma (HCC), a leading cause of mortality in people with HIV. We aimed to verify ...whether HIV affected the overall survival (OS) of patients with HCC, independent of treatment and geographic origin.
We designed an international multicohort study of patients with HCC accrued from four continents who did not receive any anticancer treatment. We estimated the effect of HIV seropositivity on patients' OS while accounting for common prognostic factors and demographic characteristics in uni- and multivariable models.
A total of 1,588 patients were recruited, 132 of whom were HIV positive. Most patients clustered within Barcelona Clinic Liver Cancer (BCLC) C or D criteria (n = 1,168 74%) and Child-Turcotte-Pugh (CTP) class B (median score, 7; interquartile range IQR, 3). At HCC diagnosis, the majority of patients who were HIV-positive (n = 65 64%) had been on antiretrovirals for a median duration of 8.3 years (IQR, 8.59 years) and had median CD4
cell counts of 256 (IQR, 284) with undetectable HIV RNA (n = 68 52%). OS decreased significantly throughout BCLC stages 0 to D (16, 12, 7.5, 3.1, and 3 months, respectively; P < .001). Median OS of patients who were HIV-positive was one half that of their HIV-uninfected counterparts (2.2 months bootstrap 95% CI, 1.2 to 3.1 months v 4.1 months 95% CI, 3.6 to 4.4 months). In adjusted analyses, HIV seropositivity increased the hazard of death by 24% ( P = .0333) independent of BCLC ( P < .0001), CTP ( P < .0001), α-fetoprotein ( P < .0001), geographical origin ( P < .0001), and male sex ( P = .0016). Predictors of worse OS in patients who were HIV-positive included CTP ( P = .0071) and α-fetoprotein ( P < .0001).
Despite adequate antiretroviral treatment, HIV seropositivity is associated with decreased survival in HCC, independent of stage, anticancer treatment, and geographical origin. Mechanistic studies investigating the immunobiology of HIV-associated HCC are urgently required.
The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. We compared the presenting features and outcome of HCC in elderly (>or=70 years) and younger ...patients (<70 years).
Multicentre retrospective cohort study and nested case-control study. Patients 614 elderly and 1104 younger patients from the ITA.LI.CA database, including 1834 HCC cases consecutively diagnosed from January 1987 to December 2004. Both groups were stratified according to treatment: hepatic resection, percutaneous procedures, transarterial chemoembolisation (TACE). Survival was assessed in the whole population and in each treatment subgroup. Age, sex, aetiology, cirrhosis, comorbidities and cancer stage (CLIP score) were tested as predictors of survival. In each subgroup, differences in patient survival were also assessed after adjustment and matching by propensity score.
Ageing was associated with a higher prevalence of comorbidities, better liver function and CLIP score. Regardless of age, two-thirds of patients underwent radical treatments or TACE. Elderly patients underwent more ablative procedures and fewer resections or TACE sessions. The survival of elderly and younger patients was comparable in each treatment subset, and was predicted by CLIP score. This result was confirmed by the propensity analysis.
The overall applicability of radical or effective HCC treatments was unaffected by old age. However, treatment distribution differed, elderly individuals being more frequently treated with percutaneous procedures and less frequently with resection or TACE. Survival was unaffected by age and primarily predicted by cancer stage, assessed by the CLIP system, both in the overall population and in treatment subgroups.