Malignant pleural mesothelioma (MPM) is often associated with asbestos exposure and carries an extremely poor prognosis (1). The mean latency of MPM following asbestos exposure is 40 years (1). Although several non-surgical treatments for MPM are available, the role of surgery is still important (1). Extra-pleural pneumonectomy (EPP) has long been considered a radical approach; however, the Mesothelioma and Radical Surgery (MARS) study reported that EPP has a 14.4-month median survival and might harm patients (2). Thereafter extended pleural decortication (PD) was recommended over EPP due to fewer complications (1).

PD entails removal of the parietal and visceral pleura with sparing of the pulmonary parenchyma in an effort to excise all macroscopic tumors (3). Patients with PD have lower complication and mortality rates than patients with EPP; however, complete resection (R0) is extremely difficult with little improvement in prognosis (3). As additional intraoperative treatment, photodynamic therapy (PDT) can improve the prognosis of patients with MPM (4); however, PDT is currently not authorized for use in patients with MPM in Japan.

Argon plasma coagulation (APC) is effective for tumor resection or hemostasis with minimal complications and is commonly used for treatment of endobronchial tumors (5-7); however, there are no reports involving the use of APC in the treatment of MPM. We have mainly used APC for hemostasis during PD since 2015, and we recently noticed an anti-tumor effect for patients with MPM. The aim of this study was to determine the effectiveness of APC in the treatment of patients with MPM who undergo a radical PD.

PD for patients with MPM is considered less invasive compared to EPP, and PD is recommended for some patients over EPP (1); however, PD alone is not sufficient to cure MPM because the goal of surgery in patients with MPM is to achieve macroscopic complete resection, while multimodal treatments, including additional intraoperative treatments for local control, have been attempted (1,4). Friedberg et al (4) performed PDT therapy after radical pleurectomy with good outcomes and concluded that PDT might have a role in extending survival via direct cell death, breakdown of tumor neovasculature, and/or the immune response, although PDT does not appear to have a positive impact on local control (4). Unfortunately, PDT cannot be used for patients with MPM in Japan due to a lack of social insurance system coverage.

APC is considered a minimally invasive procedure with fewer complications compared to the Nd-YAG laser. APC is commonly used for treatment of endobronchial tumors given the benefits of minimal smoke and good visual control (7). APC is useful for intraoperative hemostasis without severe complications, and APC results for tumors may be equal to the reported laser results (7).

We have mainly used APC for hemostasis during PD since 2015 and we recently noticed an anti-tumor effect among patients with MPM. Although APC is useful for intraoperative hemostasis in patients with MPM, our study showed that APC may have an anti-tumor effect secondary to coagulation. In the present study 1 patient survived 5 years and 3 patients had disease-free survival with the median overall survival of 18.5 months and the median disease-free survival of 11.1 months. A prior phase I trial of intraoperative hyperthermic treatments using cisplatin and gemcitabine for MPM revealed that the median overall and recurrence-free survival times were 20.3 and 10.7 months, respectively, the results of which were similar to our results (8), although chemotherapy of pemetrexed plus cisplatin for MPM revealed the median overall survival of 16.1 months (9). Our study revealed longer median survival compared to group with chemotherapy alone. Considering the rationale underlying PD is to achieve macroscopic complete resection without microscopic complete resection, this is the first report demonstrating the usefulness of APC for patients with MPM. Indeed, there are few reports involving experimental or feasibility studies combined with hyperthermic intrathoracic chemoperfusion therapy on cold plasma coagulation (10,11). Hoffman et al (11) reported the feasibility of cold plasma coagulation using helium gas and several adverse events were reported; however, there was no reference to the prognostic impact of cold plasma coagulation. In contrast, no complications were associated with APC. Although Hoffman et al (11) combined cold plasma coagulation with hyperthermic intrathoracic chemoperfusion therapy, we did not and only performed APC intraoperatively. Although APC differs from cold plasma coagulation, the adverse events reported in the Hoffman et al study (11) might be related to a combination of hyperthermic intrathoracic chemoperfusion therapy.

The reason why our results revealed no complications related to APC might be because we exercised caution in protecting nerves, vessels, and the pericardium from the APC during radical PD. Indeed, normal organs must be protected from collateral injury during APC.

We acknowledge the limitations of this study. Our study had a retrospective single arm and consisted of a small cohort, which limited the generalizability of our results. Because this study was retrospective, we could not get patients' consents. The potential participants were given the opportunity to decline to be further enrolled in the study (opt-out). However, despite these limitations, we did not report any adverse events associated with APC and the outcomes were favorable.

We believe that APC may be able to be selected as a potential intraoperative adjuvant treatment for MPM due to the potential anti-tumor effects. We look forward to evaluating our findings in a larger and multi-center study involving APC in patients with MPM.