PITAC: Pressurized Intrathoracic Aerosol Chemotherapy

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Pressurized intrathoracic aerosol chemotherapy (PITAC) is a novel and promising treatment for malignant pleural effusion, allowing surgeons to achieve an effective pleurodesis together with a potential anti-neoplastic effect. The treatment delivers chemotherapeutic agents via a nebulizer into the thoracic cavity, where a therapeutic aerosol is formed. 

PITAC rationale is based on physical properties such as the homogeneous distribution of a gas within a closed space and creating a pressure gradient to overcome the tumor interstitial fluid pressure, which enhances in-tissue drug penetration. This procedure is performed using VATS, incorporating all the advantages of a minimally invasive approach. In addition, a low dose of chemotherapeutic drugs is administered with no systemic toxicity.

Given these advantages, PITAC may soon represent a pioneering treatment in the field of loco-regional therapy for pleural carcinomatosis. This video presents a demonstration of the procedure.



First, the patient was laid in the lateral decubitus position under general anesthesia. Two 12 mm balloon trocars were positioned in the chest wall, one in the seventh intercostal space (ICS) in the mid-axillary line and one in the fifth ICS in the anterior axillary line. The camera was inserted through the trocar at the seventh ICS. A standard thoracoscopy was then performed with a careful exploration of the entire thoracic cavity. Balloon trocars were required to create a closed system and avoid pressurized aerosol dispersal outside the thoracic cavity. After MPE removal and lysis of eventual pleural adhesions, multiple parietal pleural biopsies were sampled as common practice. In patients without a preoperative diagnosis of pleural carcinomatosis, pathologic confirmation should be obtained by intraoperative frozen section.

A dedicated checklist containing all safety aspects of the PITAC procedure was double checked before administration of chemotherapy drugs. CO2 was used to pressurize the pleural space and the gas was inflated into thoracic cavity by the trocar at the fifth ICS. The dedicated CE-certified nebulizer in surgical stainless steel was then inserted through the trocar at the fifth ICS and connected to a high pressure injector. Cytostatic solutions were prepared according to the patient’s body surface area (BSA), calculated with the Boyd formula, and were then drawn into the injector syringe. Before starting the nebulization, the patient was covered with a sterile drape to minimize operating room air contamination with aerosol chemotherapeutic agents.

Next, all the staff left the operating room (OR) to prevent eventual exposure to chemotherapy. Using a remote control, cisplatin (10.5 mg/m2 in 150 mL NaCl 0.9 percent) and doxorubicin (2.1 mg/m2 in 50 mL NaCl 0.9 percent) were aerosolized into the pleural cavity at 0.7 mL/s flow with a maximal upstream pressure of 220 PSI. This closed system was left in a steady state for 30 minutes at 37 °C under a constant intrathoracic pressure of 12 mmHg CO2 to increase drug penetration into the neoplastic tissue. Cisplatin and doxorubicin were selected for both direct cytotoxic and sclerosing effects on pleural layers.

Vital signs and the nebulization procedure were remote controlled by both surgeons and anesthesiologists from outside the OR, even though there is no significant inhalation risk. At the end of 30 minutes of nebulization, the staff entered the OR to remove the remaining toxic aerosol using a closed surgical smoke evacuation system with two microparticle filters to capture residual molecules. 

Next, the pleural space was carefully explored to check hemostasis. The trocar ballons were then deflated and retracted under vision control. Finally, two chest drains were placed and the lung was ventilated.

To conclude, PITAC is a safe, feasible, and effective technique to control malignant pleural effusion recurrence. Further investigations should also assess its oncological role. PITAC might represent a pioneering treatment in the field of locoregional therapy for pleural carcinomatosis.

References

1. Clive AOJ, Bhatnagar R, Preston NJ, et al. Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev 2016;5:CD010529.
2. Bibby AC, Dorn P, Psallidas I, Porcel JM, Janssen J, Froudarakis M et al. ERS/EACTS statement on the management of malignant pleural effusions. Eur J Cardiothorac Surg 2018; doi:10.1093/ejcts/ezy258.
3. Solass W, Hetzel A, Nadiradze G, Sagynaliev E, Reymond MA. Description of a novel approach for intraperitoneal drug delivery and the related device. Surg Endosc 2012;26(7):1849–55.
4. Solass W, Giger-Pabst U, Zieren J, Reymond MA. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): occupational health and safety aspects. Ann Surg Oncol 2013;20(11):3504–11.
5. Solass W, Kerb R, Murdter T, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy. Ann Surg Oncol 2014; 21(2):553–9.
6. B. Tempfer, G. Winnekendonk, W. Solass et al. Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: a phase2 study. Gynecologic Oncology, vol. 137, no. 2, pp. 223–228, 2015.
7. Kuchen N, Cereser T, Hailemariam S and Schoeb O. Safety and efficacy of pressurized intraperitoneal/intrathoracic aerosol chemotherapy (PIPAC/PITAC) in patients with peritoneal and/or pleural carcinomatosis: A preliminary experience. J Med Therap. 2018; 2(1): 1-6.
8. Drevet G, Maury JM, Bakrin N, Tronc F. Technique of pressurized intrathoracic aerosol chemotherapy (PITAC) for malignant pleural effusion. Pleura Peritoneum. 2020 Nov 9;5(4):20200129.
9. Tempfer CB, Giger-Pabst U, Seebacher V, Petersen M, Dogan A, Rezniczek GA. A phase I, single-arm, open-label, dose escalation study of intraperitoneal cisplatin and doxorubicin in patients with recurrent ovarian cancer and peritoneal carcinomatosis. Gynecol Oncol 2018; 150: 23–30.
10. Mazumdar M, Smith A, Schwartz LH. A statistical simulation study finds discordance between WHO criteria and RECIST guideline. J Clin Epidemiol. 2004 Apr;57(4):358-65.

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