Current concepts in hepatic resection for hepatocellular carcinoma in cirrhotic patients

Hepatocellular carcinoma(HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with liver cirrhosis.Liver resection is considered the most potentially curative therapy for HCC patients when liver transplantation is not an option or is not immediately accessible.This review is aimed at investigating the current concepts that drive the surgical choice in the treatment of HCC in cirrhotic patients;Eastern and Western perspectives are highlighted.An extensive literature review of the last two decades was performed,on topics covering various aspects of hepatic resection.Early post-operative and long-term outcome measures adopted were firstly analyzed in an attempt to define an optimal standardization useful for research comparison.The need to avoid the development of post-hepatectomy liver failure represents the "conditio sine qua non" of surgical choice and the role of the current tools available for the assessment of liver function reserve were investigated.Results of hepatic resection in relationship with tumor burden were compared with those of available competing strategies,namely,radiofrequency ablation for early stages,and trans-arterial chemoembolization for intermediate and advanced stages.Finally,the choice for anatomical versus non-anatomical,as well as the role of laparoscopic approach,was overviewed.The literature review suggests that partial hepatectomy for HCC should be considered in the context of multi-disciplinary evaluation of cirrhotic patients.Scientific research on HCC has moved,in recent years,from surgical therapy toward non-surgical approaches and most of the literature regarding topics debated in the present review is represented by observational studies,whereas very few well-designed randomized controlled trials are currently available;thus,no robust recommendations can be derived.

Surveillance for early diagnosis of hepatocellular carcinoma: How best to do it?

Surveillance for hepatocellular carcinoma(HCC)is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy.Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments.Repetition of liver ultrasonography(US)every 6 mo is the recommended surveillance program to detect early HCCs,and a positive US has to entrain a well-defined recall policy based on contrast-enhanced,dynamic radiological imaging or biopsy for the diagnosis of HCC.Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance,the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure.Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC.The promotion of specific educational programs for practitioners,clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.

How albumin administration for cirrhosis impacts on hospital albumin consumption and expenditure

AIM:To assess the impact of guidelines for albumin prescription in an academic hospital,which is a referral center for liver diseases.METHODS:Although randomized trials and guidelines support albumin administration for some complications of cirrhosis,the high cost of albumin greatly limits its use in clinical practice.In 2003,a multidisciplinary panel at Sant'Orsola-Malpighi University Hospital(Bologna,Italy)used a literature-based consensus method to list all the acute and chronic conditions for which albumin is indicated as first-or second-line treatment.Indications in hepatology included prevention of post-paracentesis circulatory dysfunction and renal failure induced by spontaneous bacterial peritonitis,and treatment of hepatorenal syndrome and refractory ascites.Although still debated,albumin administration in refractory ascites is accepted by the Italian health care system.We analyzedalbumin prescription and related costs before and after implementation of the new guidelines.RESULTS:While albumin consumption and costs doubled from 1998 to 2002,they dropped 20%after 2003,and remained stable for the following 6 years.Complications of cirrhosis,namely refractory ascites and paracentesis,represented the predominant indications,followed by major surgery,shock,enteric diseases,and plasmapheresis.Albumin consumption increased significantly after guideline implementation in the liver units,whereas it declined elsewhere in the hospital.Lastly,extra-protocol albumin prescription was estimated as<10%.CONCLUSION:Albumin administration in cirrhosis according to international guidelines does not increase total hospital albumin consumption if its use in settings without evidence of efficacy is avoided.

Serum SCCA-IgM as a predictor of hepatocellular carcinoma in patients with liver cirrhosis

Aberrant Squamous Cell Carcinoma Antigen (SCCA) expression is an early hepatocarcinogenetic event and circulating SCCA-IgM complexes are elevated in most HCC patients. We evaluated whether serum SCCA-IgM levels can identify HCV +ve cirrhotic patients at low HCC risk. In this retrospective study we enrolled 29 cirrhotic patients in whom serum SCCA-IgM was measured 8 - 69 months (median 31) before HCC diagnosis, and 28 cirrhotic patients who remained HCC- free, with SCCA-IgM measured 15 - 68 months (median 48) before the study end. The best discriminating value of SCCA-IgM was calculated and tested in predicting HCC diagnosis within 12, 24 and 36 months. Sensitivity analysis, considering different HCC incidence, was conducted to identify the patient subgroup with an annual cancer risk below the threshold of a cost-effective semiannual surveillance with ultrasound. Cumulative HCC incidence at 12, 24 and 36 months was 7.0%, 15.7% and 26.3%, respectively. SCCA-IgM levels were higher in HCC than in cirrhotic patients [median: 381 (95% C.I.: 50 - 5289) vs. 100 (70 - 493) AU/mL, P = 0.005]. The SCCA-IgM value ≤ 200 AU/mL accurately identified patients at low risk of HCC development in the subsequent year (sensitivity 75%, specificity 62%, positive predictive value 13% and negative predictive value 97%). Considering an annual HCC incidence ≤ 3%, patients with SCCA-IgM ≤ 200 AU/mL (60% of the whole patients) had an HCC risk below the accepted threshold of a cost-effective surveillance (1.5%). In conclusion, provided that our provocative results are confirmed in larger studies, SCCA-IgM serum measurement could permit implementation of a two step (with different costs) surveillance: an initial serological surveillance, based on the annual monitoring of this biomarker, and the conventional surveillance by semiannual US when SCCA-IgM becomes >200 AU/mL. This could improve the cost/effectiveness of surveillance of HCV infected patients at risk of HCC.

Ramucirumab as a second-line treatment for hepatocellular carcinoma: reaching out further to patients with elevated alpha-fetoprotein

Hepatocellular carcinoma(HCC)occurs at a rate of 3-5%per year in patients with compensated cirrhosis,and itoften represents the first disease complication and themain cause of death in these patients(1).Surveillance forHCC is recommended by all liver disease associations,as it increases patient survival mainly as a result of earlydiagnosis of the tumour,allowing most patients to conveyto curative treatments(2,3).