Background & Aims Transarterial chemoembolisation (TACE) improves survival of properly selected patients with hepatocellular carcinoma (HCC). Drug eluting beads (DEB) provide a calibrated and ...homogenous procedure while increasing efficacy. Outcome data applying this technology is lacking, and this is instrumental for clinical decision-making and for trial design. We evaluated the survival of HCC patients treated with DEB-TACE following a strict selection (preserved liver function, absence of symptoms, extrahepatic spread or vascular invasion). Methods We registered baseline characteristics, the development of treatment-related adverse events, and the overall survival of all HCC patients treated by DEB-TACE from February 2004 to June 2010. Results One hundred and four patients were treated with DEB-TACE. All but one were cirrhotic, 62.5% HCV+, 95% Child-Pugh A, 41 BCLC-A and 63 BCLC-B. Causes of DEB-TACE treatment in BCLC-A patients were: 35 unfeasible ablation, and six post-treatment recurrences. After a median follow-up of 24.5 months, 38 patients had died, two patients had received transplantation and 24 had received sorafenib because of untreatable tumour progression. Median survival of the cohort was 48.6 months (95% CI: 36.9–61.2), while it was 54.2 months in BCLC stage A and 47.7 months in stage B. Median survival after censoring follow-up at time of transplant/sorafenib was 47.7 (95% CI: 37.9–57.5) months. Conclusions These data validate the safety of DEB-TACE and show that the survival expectancy applying current selection criteria and technique is better than that previously reported. A 50% survival at 4 years should be considered when suggesting treatment for patients fitting into controversial scenarios such as expanded criteria for transplantation/resection for multifocal HCC.
Management of HCC de Lope, Carlos Rodríguez; Tremosini, Silvia; Forner, Alejandro ...
Journal of hepatology,
2012, 2012-00-00, 2012-1-00, 20120101, Letnik:
56
Journal Article
Recenzirano
Summary Hepatocellular carcinoma (HCC) is a highly prevalent and lethal neoplasia, the management of which has significantly improved during the last few years. A better knowledge of the natural ...history of the tumor and the development of staging systems that stratify patients according to the characteristics of the tumor, the liver disease, and the performance status, such as the BCLC (Barcelona Clinic Liver Cancer) system, have led to a better prediction of prognosis and to a most appropriate treatment approach. Today curative therapies (resection, transplantation, ablation) can improve survival in patients diagnosed at an early HCC stage and offer a potential long-term cure. Patients with intermediate stage HCC benefit from chemoembolization and those diagnosed at advanced stage benefit from sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative effects. In this article we review the current management in HCC and the new advances in this field.
Epidemiology, risk factors, and clinical effect of infections by multiresistant bacteria in cirrhosis are poorly known. This work was a prospective evaluation in two series of cirrhotic patients ...admitted with infection or developing infection during hospitalization. The first series was studied between 2005 and 2007 (507 bacterial infections in 223 patients) and the second between 2010 and 2011 (162 bacterial infections in 110 patients). In the first series, 32% of infections were community acquired (CA), 32% healthcare associated (HCA), and 36% nosocomial. Multiresistant bacteria (92 infections; 18%) were isolated in 4%, 14%, and 35% of these infections, respectively (P < 0.001). Extended‐spectrum β‐lactamase‐producing Enterobacteriaceae (ESBL‐E; n = 43) was the main multiresistant organism identified, followed by Pseudomonas aeruginosa (n = 17), methicillin‐resistant Staphylococcus aureus (n = 14), and Enterococcus faecium (n = 14). The efficacy of currently recommended empirical antibiotic therapy was very low in nosocomial infections (40%), compared to HCA and CA episodes (73% and 83%, respectively; P < 0.0001), particularly in spontaneous bacterial peritonitis, urinary tract infection, and pneumonia (26%, 29%, and 44%, respectively). Septic shock (26% versus 10%; P < 0.0001) and mortality rate (25% versus 12%; P = 0.001) were significantly higher in infections caused by multiresistant strains. Nosocomial origin of infection (hazard ratio HR, 4.43), long‐term norfloxacin prophylaxis (HR, 2.69), recent infection by multiresistant bacteria (HR, 2.45), and recent use of β‐lactams (HR, 2.39) were independently associated with the development of multiresistant infections. Results in the second series were similar to those observed in the first series. Conclusions: Multiresistant bacteria, especially ESBL‐producing Enterobacteriaceae, are frequently isolated in nosocomial and, to a lesser extent, HCA infections in cirrhosis, rendering third‐generation cephalosporins clinically ineffective. New antibiotic strategies tailored according to the local epidemiological patterns are needed for the empirical treatment of nosocomial infections in cirrhosis. (HEPATOLOGY 2012)
The aim of this study was to describe the imaging features by contrast‐enhanced ultrasound (CEUS) of intrahepatic cholangiocarcinoma (ICC) in cirrhosis patients. We registered the CEUS images of ...cirrhosis patients with histologically confirmed ICC. In all cases magnetic resonance imaging (MRI) was done to confirm the diagnosis and/or staging purposes. A total of 21 patients met all the criteria to be included in the study. The median nodule size was 32 mm. All nodules showed contrast enhancement at arterial phase; in 10 cases it was homogeneous and in 11 cases peripheral (rim‐like). All nodules displayed washout during the venous phases; it appeared during the first 60 seconds in 10 nodules, between 60‐120 seconds in five cases, and in six cases after 2 minutes. Ten nodules (five larger than 2 cm) displayed homogeneous contrast uptake followed by washout and they correspond to the specific pattern of hepatocellular carcinoma according to the American Association for the Study of Liver Diseases criteria. However, none of these lesions displayed washout on MRI. Conclusion: CEUS should not be used as the sole imaging technique for conclusive hepatocellular carcinoma diagnosis and if the MRI does not display the diagnostic vascular pattern, a confirmatory biopsy is mandatory. Hepatology 2010;51:2020–2029
Staging and treatment indication are relevant topics in the management of patients with hepatocellular carcinoma (HCC) and for optimal results, they have to take into account liver function, tumor ...stage, and physical status. For any staging system to be meaningful it has to link staging with treatment indication; this should be based on robust scientific data. Currently, the sole proposal that serves both aims is the Barcelona Clinic Liver Cancer (BCLC) approach. It takes into account the relevant parameters of all important dimensions and divides patients into very early/early, intermediate, advanced, and end-stage. Early-stage HCC patients should be considered for potentially curative options such as resection, ablation, and transplantation. Patients at intermediate stage benefit from chemoembolization, whereas patients at an advanced stage, or who cannot benefit from options of higher priority, have sorafenib as the standard treatment. Finally, patients at end-stage should merely receive palliative care.
This study assesses the magnetic resonance (MR) features of intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis with specific analysis of the contrast enhancement pattern. ...Cholangiocarcinoma may show increased contrast uptake in the arterial phase, and, if washout in the delayed venous phase were to be detected, the noninvasive diagnostic criteria proposed in the American Association for the Study of Liver Diseases guidelines would be refuted. We reviewed the MR findings of 25 patients with cirrhosis with 31 histologically confirmed ICC nodules. Signal intensity on basal T1‐weighted and T2‐weighted images and characteristics of enhancement after contrast administration on arterial, portal, and delayed phase were registered. Enhancement pattern was defined according to the behavior of the lesions in each phase, and dynamic pattern was described according to the progression of enhancement throughout the different phases. The most frequent pattern displayed by ICC was a progressive contrast uptake (80.6%). Stable contrast enhancement was registered in 19.4%. None of the ICCs showed a washout pattern, a profile that is specific for hepatocellular carcinoma (HCC). The ICC dynamic behavior differed significantly according to tumor size: progressive enhancement pattern was the most frequent (20 of 25 cases) in lesions larger than 20 mm, whereas the stable pattern was mainly identified in nodules smaller than 20 mm. The most characteristic MR contrast pattern in ICC in cirrhosis is a progressive contrast uptake throughout the different phases, whereas contrast washout at delayed phases is not observed. Because stable enhancement pattern without washout also can be registered in small HCC nodules, the evaluation of delayed phase is mandatory for a proper nodule characterization. If washout is not registered, a biopsy should be mandatory for diagnosis. (HEPATOLOGY 2009.)
This is an updated review of screening, early diagnosis and treatment of hepatocellular carcinoma, focusing on the advancements occurred in the last years and highlighting the challenges in clinical ...research. Hepatocellular carcinoma (HCC) is nowadays the sixth most frequent cancer worldwide with up to 740,000 new cases diagnosed each year, and it is the third most prevalent cause of cancer-related-death worldwide (1). This neoplasm usually appears linked to an underlying liver disease, being one of the most relevant causes of death in patients diagnosed of liver cirrhosis (2,3). In the last years, important advancements in terms of diagnosis, staging and treatment of HCC, improving the management and outcome of the disease, have been made (4-7). Despite the fact that these improvements have absolutely changed natural history of HCC, there are several areas that still need further advancements. The aim of this document is to discuss some controversial aspects, which in our opinion constitute real challenges in clinical research of HCC.
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•The risk of HCC in patients with HCV cirrhosis treated with DAAs persists despite viral cure.•The presence of indeterminate nodules before starting DAA is associated with a 3 times ...greater risk of HCC.•A time association between DAA therapy and developing HCC reflects increased short-term HCC risk.•DAA therapy elicits a mechanism that primes the emergence of HCC early during follow-up.
Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC.
This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years.
A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96–4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55–5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased.
These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation.
In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased.
Evaluation of response to treatment is a key aspect in cancer therapy. Response Evaluation Criteria in Solid Tumors (RECIST) are used in most oncology trials, but those criteria evaluate only ...unidimensional tumor measurements and disregard the extent of necrosis, which is the target of all effective locoregional therapies. Therefore, the European Association for the Study of the Liver (EASL) guidelines recommended that assessment of tumor response should incorporate the reduction in viable tumor burden. The current report provides an assessment of the agreement/concordance between both RECIST and the EASL guidelines for the evaluation of response to therapy.
The authors evaluated a cohort of 55 patients within prospective studies, including 24 patients with hepatocellular carcinoma who underwent transarterial chemoembolization (TACE) with drug eluting beads (DEB-TACE) and 31 patients who underwent percutaneous ablation (percutaneous ethanol injection PEI/radiofrequency RF). Triphasic helical computed tomography scans were performed at baseline, at 1 month, and at 3 months after procedure, and 2 independent radiologists evaluated tumor response.
Evaluating response according to RECIST criteria, no patients achieved a complete response (CR), 21.8% of patients achieved a partial response (PR) (none in the PEI/RF group), 47.3% of patients had stable disease (SD), and 30.9% of patients had progressive disease (PD). When response was evaluated according to the EASL guidelines, 54.5% of patients achieved a CR, 27.3% of patients achieved a PR, 3.6% of patients had SD, and 14.5% had PD. The kappa coefficient was 0.193 (95% confidence interval, 0.0893-0.2967; P < .0001).
RECIST missed all CRs and underestimated the extent of partial tumor response because of tissue necrosis, wrongly assessing the therapeutic efficacy of locoregional therapies. This evaluation should incorporate the reduction in viable tumor burden as recognized by nonenhanced areas on dynamic imaging studies.
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