Patients and study design
This was a retrospective study to analyze the clinical efficacy and survival benefit of intrapleural hyperthermic perfusion using distilled water to treat malignant pleural effusion. The records of patients with malignant pleural effusion who admitted to department of cardiothoracic surgery of Taizhou Hospital between January 2014 and December 2018 were reviewed. All patients received intrapleural hyperthermic perfusion using distilled water. Eligible criteria included patients aged ≥18 years and MPE confirmed by chest X-ray and/or computed tomography (CT) investigation, pleural cytology and/or biopsy. Patients’ cardiorespiratory function was able to tolerate general anesthesia. All patients underwent thorough examination before surgery including medical history, physical examination, computed tomography scan of the chest and abdomen, magnetic resonance scan of the brain, general bone scintigraphy to evaluate the primary tumor and metastases sites. The clinical stage of these patients was evaluated according to the eighth edition of the American Joint Committee on Cancer TNM staging. All patients signed an informed consent form.
The response of treatment was defined as follows: 1. complete response (CR; no re-accumulation of pleural effusion after IPH for at least four weeks); 2. partial response (PR; pleural effusion was reduced by 50% and this situation was sustained for four weeks; 3. no consequence (NC; pleural effusion was not reduced.
Surgical technique
VATS was performed for every patient under general anesthesia with double lumen endotracheal tubes ventilation. The vital signs were monitored through electrocardiogram. Invasive pressure and end tidal CO2 (etCO2) were also monitored. The patient was placed at 90°of lateral position. A 4 cm and 1 cm incision were made at the fourth and seventh intercostal space along the anterior and middle axillary line, separately, the latter of which was used for drainage after surgery. A trocar was inserted into the pleural cavity. Then, thoracoscope was put through the port and used to explore the pleural cavity for the extent of adhesion and tumor involvement. The adhesions, fibrinoid membrane restraining lung re-expansion and pleural effusion was removed with thoracoscopic equipment. Enough disseminated tumor tissues were achieved for biopsy. Then, 32F and 28F chest tubes were inserted into the above two ports as inflow and outflow catheters. The tubes were fixed to the chest wall with sutures and connected to a standard extracorporeal circuit (roller pump, heat exchanger and reservoir). A temperature sensor was put into the thoracic cavity for real-time monitoring.
Perfusion technique
After the procedure inside the thorax, the tubes were connected to the perfusion system and the extracorporeal circulation was started. The heating circuit system had preheated the distilled water to 43℃ in advance. Then the pleural cavity began to perfuse and the ipsilateral lung collapsed. The flow rate was set between 1000 and 1500 ml/min. The temperature of the pleural cavity was maintained around 43℃. The perfusion procedure continued for 60 minutes. After perfusion, the thoracoscope was used to confirm no active bleeding, pulmonary air leakage. A 26F chest tube was placed through the seventh intercostal port in the thoracic cavity for drainage.
Follow-up
Patients were followed every two weeks for the first month and every month thereafter. Chest radiographs or ultrasound were done during the follow up. All patients were followed until they died. Survival was calculated from the date of surgery. The information of pleural effusion and overall survival were retrieved.
Statistical analysis
Data were presented as the mean ± standard deviation or the median and range. Overall survival was analyzed using Kaplan-Meier method with log-rank tests. The volume of pleural effusion was estimated through a three Dimension reconstruction of computed tomography of the chest with the software of Mimics Medical version 19.0 (Materialise, Belgium). IBM SPSS version 22.0 (IBM SPSS, lnc, Chicago, IL) was used for calculation. The Kaplan-Meier method with the log-rank test was used for survival analysis. The COX proportional hazards regression model was applied to perform univariate and multivariate analyses, and those variables that achieved a value of P <0.2 in univariate analysis were entered into the multivariable analysis. All statistical tests were 2-sided and a value of P <0.05 was considered to be statistically significant.