Introduction

In recent years, radiofrequency interstitial thermal ablation (TA) has been performed with good results in patients with hepatocellular carcinoma (HCC). Furthermore, while TA is most commonly performed through a percutaneous approach [1, 2], there is a sub-group of patients who may benefit from a laparoscopic thermoablation (LTA) approach [3]. The rationale of this technique is to combine the advantages of an improved staging allowed by the intracorporeal ultrasound examination [4] with a safe approach to liver lesions difficult or impossible to be treated percutaneously [3]. The aim of our review was to evaluate the advantages and limits of the laparoscopic approach according the criteria of the evidence-based medicine (www.cebm.net). A systematic research of PubMed, Science Citation Index, and Embase databases was accomplished for articles published before October 2019. We identified 29 articles using the keywords “laparoscopic radiofrequency and hepatocellular carcinoma” and “laparoscopic microwave and hepatocellular carcinoma” to obtain all studies useful for this review analysis. Manual cross-referencing was accomplished, and we also analyzed the reference lists of the included articles to identify further undetected studies. Case reports and abstracts were excluded. Table 1 shows the characteristics of these 29 studies [4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32].

Table 1 Characteristics of selected studies
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Basing on its peculiar characteristics, the LTA should be able:

  • To stage the intrahepatic HCC disease at best using laparoscopic ultrasound (LUS) [33];

  • To treat patients at risk of unsuccessful therapy through a percutaneous access;

  • To treat safely those patients at risk of complications;

  • To improve the thermoablation results (total necrosis and tumor recurrence).

Staging of the intrahepatic disease

Although intraoperative ultrasound (IOUS) is the most effective tool for detecting focal liver lesions [34], this technique has shown remarkable amount of false positive for what concern HCC definition in cirrhotic patients [35]. The introduction of second-generation US contrast agents, has improved the accuracy of IOUS in this specific field [36]. This technique via laparoscopic approach so-called laparoscopic ultrasound (LUS) uses a linear array high-resolution (7.5 MHz) transducers mounted on probes that are introduced through standard 11.0 mm trocars. Even if few papers have been reported, LUS shown a great value in HCC diagnosis and staging (Table 2); better staging, by detecting new suspect HCC in 8–22% of cases [6, 7, 10, 12, 17, 26], means to avoid unnecessary laparotomy with a remarkable percentage of patients (16.5%) as reported by Lai et al. who shown 44 out of 122 consecutive patients with HCC and liver cirrhosis found to be unresectable after laparoscopic staging [37]. Authors concluded that LUS have a significant effect both on identifying surgically untreatable disease and in selecting the optimal treatment strategy. The key point is to be sure of histology of new suspect HCC found by LUS.

Table 2 Studies with staging liver tumors with LUS
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Moreover, Ido et al. [38] reported power of LUS in detecting new suspect HCC nodules in 64 out of 186 patients (34.4%); LUS guided biopsy was made on all 134 new lesions with a histological confirm in 28 cases (21%). Nevertheless, this quite low yield of LUS in detecting true HCCs, the authors outlined that when new nodular lesions are detected by LUS, these patients must be considered at high risk for recurrence, even if there is no histological evidence of HCC. We reported similar results in our personal series with 22% out of 68 patients submitted to LUS showing new malignant nodules. These findings support the validity of a single-stage approach with discovery and immediate treatment of new HCC nodules allowed by the LUS use [26].

Moreover, Klegar et al. [39] remarked high yield of LUS in changing operative management in 9/20 (45%) of HCC scheduled for liver resection. Management was changed because of LUS finding of severe nodular cirrhosis in four cases, more extensive staging in six cases either for number of nodules or for intrahepatic satellites metastases or carcinomatosis discover. On the contrary LUS shown a down staging in two cases, thus allowing a gentler procedure.

Among opponents of considering LUS as a crucial staging tool in HCC surgical treatment, Reddy et al. [40] reported his experience on 16 patients scheduled for liver transplantation (LT), all submitted to LUS as first step, thus showing to be suitable to LT in 100% of cases. Finally, at laparotomy, one patient was found to have extrahepatic disease; thus, the procedure was abandoned. One patient was found to have lesser curvature lymphadenopathy. Two patients had major vascular involvement noted in the explanted liver. Finally, authors concluded that laparoscopy cannot be routinely performed as a staging tool in a pre-transplant program due to low yield.

Any way on the basis of these data, there is a reasonable evidence that laparoscopic staging is useful and may alter patient management and treatment in patients with HCC and liver cirrhosis (level 2b of evidence).

Outcomes

Fulfilling criteria for thermoablation laparoscopic approach are shown in Table 3, including patients not suitable to HR, or patients with HCC not visible to percutaneous route (liver dome) or deep next to hilum (high risk of biliary stricture), or superficial lesions juxta visceral structures (gallbladder, colon, or stomach) as regards laparoscopic approach is effective and safe, allowing the direct visualization of surrounding structures and their active protection by performing specific laparoscopic maneuvers (separating or cooling techniques) thus reducing the risk of visceral injuries [26].

Table 3 Indications for the laparoscopic approach
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Table 4 shows the outcomes in the published series. However, until 2013, the articles included few patients and the results reflect a pioneering period for the LTA. The ability to identify and treat lesions located at the dome of the liver, peripheral in the liver, or in proximity to other organs makes LTA more flexible than the percutaneous approach, while remaining minimally invasive [22, 26, 32]. However, if the percutaneous procedure is unfeasible, this can be considered a problematic situation also for the laparoscopic approach, influencing the LTA results. In the last years, as regards LTA efficacy, technical success (total necrosis) could be obtained in a single session in more than 90% of all patients and it is in the expected range (90–100%) with similar results obtained by the most important percutaneous series [1, 2, 41, 42]. On the other hand, local tumor progression (LTP) in an TA ablated site is a serious occurrence, with described rates ranging from 3.2 to 26% after RFA in percutaneous series [1, 41, 42], influenced by the tumor size and the difficult location of the nodules. Also for the laparoscopic approach, different indications (see Table 3) should influence the LTP results: in articles published in the last years, the LTP rates in the laparoscopic series ranged from 2.8 to 23%. Many of these studies have suggested that local control of the laparoscope is an advantage during LTA compared with the percutaneous approach. LTP rates shown in the LTA studies represent very good results considering the problematic locations of the HCC tumors submitted to a laparoscopic approach. Some Authors showed that subcapsular tumors and/or tumors contiguous to viscera had an independent statistical association with LTP after percutaneous ablation [22, 43, 44]. In subcapsular tumors, saline injection into the abdominal cavity could be an effective method to widen the extrahepatic space before the RFA procedure reducing the risk of visceral complications [45]. Also, in the study of De La Serna et al. [22], LTP rates are higher for HCC superficially located. However, in other studies the laparoscopic approach obtain higher rates of success for superficial lesions [26, 32], we ascribe the improved LTP rates to the fact that both LUS and direct visualization can become more precise in targeting the lesion, while the increased technical difficulty of placing percutaneously the electrode adequately for a subcapsular tumor, thus leading to incomplete ablation. Also, for lesions contiguous to viscera, they can safely be mobilized away from the target lesion decreasing the risk of LTP and complications after LTA. On the other hand, also for the laparoscopic approach, the presence of LTP after treatment of deep-sited lesions remains a real problem: larger studies should confirm that this approach could improve LTP and technique effectiveness for deep-sited nodules.

Table 4 Outcomes of laparoscopic thermoablation for HCC
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It’s mandatory to develop new laparoscopic ultrasound probes or navigation technologies able to simplify electrode insertion into the lesion, thus getting the procedure safer, more effective and reliable, and overcoming the limit of puncturing deep-sited tumors with a totally free-hand technique. Finally, LTA seems to obtain a good rate of total necrosis also in patients with lesions difficult to treat for their position (level 4 of evidence); further studies are needed to elucidate if LTA is able to obtain better results than the percutaneous approach in unselected patients.

Safe treatment of patients at risk of complications

The laparoscopic procedure proved to be feasible and safe with a low rate of serious complications [46,47,48]. In the majority of these series, severe complications rates (Dindo-Clavien classes superior to 3A and 3B) were 2% or less.

Most common complications after LTA are pulmonary affections (pneumonia and pneumothorax) due to the needle route through the wall chest, and postoperative bleeding from the abdominal wall (trocar access). The advantage of laparoscopic approach over the percutaneous via is the proper bleeding control if early recognize during operation. Moreover, there is so-called “post-ablative syndrome”, an early and transient postoperative (within 24–48 h) treatment-related side-effect, including abdominal pain, mild fever, and pleural effusion, generally not requiring any invasive treatment. Quite exceptional complications are bile duct stenosis, liver infarction, and liver abscess or failure. A very few cases of tumor seeding in the puncture route and intraperitoneal dissemination have been described.

Finally, the rate of complications is similar among both approaches (laparoscopic and percutaneous), with a mild advantage for the former especially for what concern bleeding and visceral damage control. (level 4 of evidence).

Conclusion

Laparoscopic thermoablation is an effective and safe curative treatment for HCCs not suitable to liver resection, when percutaneous approach is not feasible (level 4 of evidence).