To the best of our knowledge, this study represents the largest single-centre series on laparoscopic ablation for HCC on cirrhosis published to date 
. Our results broadly overlap with reports from other study groups, particularly concerning the safety of the procedure, with no perioperative mortality and a low incidence of specific morbidity (25%), which is comparable with other experiences 
; our conversion rate (2%) was also in line with the literature 
. Our median postoperative hospital stay was relatively short (3 days) and similar to that of other experiences 
In other experiences 
, however, LA was used in patients eligible for traditional treatments, after selecting patients according to the number and size of their nodules and the severity of their cirrhosis. Our enrolment criteria were particular in that we prospectively applied LA super-selecting patients considered unresectable or ineligible for percutaneous ablation.
The particular feature of our treatment algorithm () lay in considering a sort of “hierarchy” of therapeutic options assigning whenever possible a potentially radical therapy regardless of BCLC stage: the first option to consider was liver resection or percutaneous ablation, the second laparoscopic ablation in those for whom resection or percutaneous ablation were technically infeasible, while TACE and Sorafenib were only considered when the previous where judged infeasible due to tumour stage ().
Due to the shortage of organs in Italy and the strong epidemiological pressure of HCC 
, we considered liver transplantation as the first-line option only for Child C patients with HCC 
or young HBV positive patients with multinodular HCC, while it was considered only for second-line therapy in patients after the first-line options failed for recurrence or incomplete treatment.
This enrolment policy enabled LA to be offered as a viable alternative to resection and/or percutaneous ablation for patients with stage BCLC-A, and as a potentially radical therapeutic alternative to TACE for super-selected patients with stage BCLC-B.
The role of LA in our treatment algorithm is justified by some theoretical advantages of the laparoscopic approach with respect to the percutaneous procedures which include the ability to approach lesions adjacent to the gastrointestinal tract, gallbladder and bile ducts, or in presence of thrombocytopenia and the chance to perform intraoperative ultrasound for a more accurate targeting of the lesions. In addition, the related pneumoperitoneum allows for an up to 40% reduction in the portal venous flow, thereby enabling an increase in the size of the ablation site; and the general anaesthesia means that a higher dose of radiofrequency energy can be used, or a larger amount of absolute alcohol can be injected in the case of alcoholics, by comparison with the percutaneous approach 
In the present study, enrolled patients survived a median 34 months, while the median survival of BCLC-A and BCLC-B patients were 39 and 28 months, respectively.
Untreated patients with intermediate-stage HCC have a median survival of approximately 16 months 
. TACE improves median survival to 19–20 months in RCTs 
and is considered the standard of care for these patients.
The selected nature of our LA population, with particular reference to BCLC B, makes any comparison with historical results after TACE impossible and in this view prospective randomized clinical trials are needed.
It is pretty clear, however, that survival figures of our BCLC A patients ineligible for resection or percutaneous ablation remain in the survival ranges described after potentially radical therapies in the international literature 
. Similarly, the remarkable low prevalence of severe adverse events after LA even in BCLC B patients, associated to the relatively good long term survival suggests a genuine potential advantage of LA on TACE in homogeneous subset of patients.
As for resection and percutaneous ablation 
, also our series of HCC patients treated by LA median showed a consistent risk of tumour recurrence intrinsically related to these loco-regional procedures. In many enrolled patients, however, LA was only the first step of a multimodal sequence of therapies used to treat the tumour. This aspect and the high safety profile of LA probably explain the good survival profile of our patients despite the high incidence of local and distant recurrences. This discrepancy between outcome endpoints is frequent for HCC patients and this is why experts in this field suggest to use patient survival as primary endpoint 
to evaluate treatment efficacy.
According to recent guidelines 
, many patients enrolled in our study would be candidates for first-line liver transplantation. With this in mind, one of the main findings of our study is that LA offers these patients the chance of a potentially curative alternative to transplantation, theoretically enabling organ saving. In this study, the 5-year survival rate for stage BCLC-A (and thus potentially transplantable) cases was about 40% (): this seems to be much lower than the figure achievable with liver transplantation 
, but in actual fact, if we consider survival after the latter from the time of listing for LT, the 5-year intention-to-treat survival rate drops to 51% 
, making it comparable with the results we achieved with LA. In this perspective, allocation of BCLC A patients to LT or to other potentially radical therapies including LA, may be considered as a function of specific organ availability, waiting list time or age 
In our series, 33 patients ultimately underwent LT as second-line therapy. This policy is similar to the one adopted by Belghiti et al. 
for patients undergoing first-line resection, reserving “salvage” LT for patients who have recurrent HCC or liver failure. The results of our study thus point to a sort of “extension” of the concept of salvage transplantation as a possible strategy not only after liver resection but also after other potentially radical therapies such as LA. A similar “extension” has been recently proposed for patients undergoing percutaneous thermal ablation 
BCLC early and intermediate stages includes a wide spectrum of potential liver diseases in terms of hepatic function (from Child A-5 to Child score B-9 patients). The results we obtained on uni- and multivariate analyses demonstrate that portal hypertension, Child-Pugh score and MELD score have little influence on survival of our patients undergoing LA. This finding is in contrast with other publications on percutaneous ablation or liver resection, in which these parameters had a clearly prognostic relevance to postoperative outcome 
. Moreover, liver decompensation signs such as ascites or hyperbilirubinemia have been recently suggested as contraindications to TACE 
The most interesting aspect of our study as regards BCLC stage, therefore, is that LA proved a safe and apparently effective therapy even for patients with a moderately impaired liver function who would be suboptimal candidates for resection, percutaneous ablation, and TACE 
. Patient super-selection and the favourable pathophysiology of minimally invasive approaches may justify our findings, however, larger studies are needed to confirm such prognostic results in this therapeutic setting.
Judging from the results of our study, a serum albumin level <37 g/l and a serum α-fetoprotein level >400 g/l are parameters that can serve preoperatively as negative prognostic factors for the long-term outcome of LA, so they should be taken into account during the patient selection process in order to exploit LA to best effect in terms of patient survival. In conclusion, the results of our study suggest that LA is a safe and effective therapeutic option for HCC patients ineligible for liver resection and/or percutaneous ablation due to their tumour's characteristics (location, size and number of nodules) and/or liver mild to moderate impairment.
The present studies presents a main limitation as we did not address a specific ablation procedure, but a treatment strategy based on the laparoscopic approach as being able to overcome several of the intrinsic limits of resection and percutaneous ablation. Thus, any consideration about the superiority of RF over alcohol injection or microwave would not be consistent with the core message of our study. The main implication of our strategy proposal for HCC patients—unsuitable for resection or percutaneous ablation—is to avoid that these patients be considered immediately for liver transplantation.
The latter is a critical point since our proposal would spare a large number of organs now used to transplant patients with small HCCs and only moderately decompensated cirrhosis.
Although only randomized clinical trials can confirm which is the best first-line therapy for this particular category of HCC patients, the current drawbacks of TACE in patients with impaired liver function 
and the shortage of organs for liver transplantation 
already support the use of LA as a potential effective therapeutic option for HCC in the current clinical practice.