Volume 9, Issue 4

Objectives Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) has been suggested as a new therapy for patients with malignant pleural effusion (MPE) and/or pleural metastasis (PLM). The patients have a poor prognosis with a median survival of 3 to 12 months. We present feasibility, patient safety, and cytological/histological response assessment in PITAC-treated patients with MPE and/or PLM. Methods Patients eligible for PITAC and treated at Odense PIPAC Center were included. PITAC was performed in lateral decubitus or prone position under double-lumen endotracheal tube ventilation to allow exclusion of the lung if necessary. After positioning of the ultrasound-guided trocar, the second trocar is inserted by video-assisted thoracoscopy. MPE was evacuated and measured. Pleural lavage was performed if no or small amounts of MPE were present. MPE or pleural lavage fluid was analyzed cytologically. Visible PLM was biopsied and sent for histology assessment using a four-tiered Thoracic Regression Grading Score (TRGS). After a walkthrough of the safety checklist, the chemotherapy was nebulized followed by 30 min of passive diffusion. The chemotherapy and chemotherapy-saturated air was evacuated through a closed bag and ventilation system. Results We report data on 11 intended PITACs in five patients. Nine PITACs were completed and two PITACs were discontinued due to intraoperative complications or technical reasons. Response evaluation was available in three patients: one showed complete response (TRGS 1) and another stable disease (TRGS 2). Cytology was available from two patients: one showed conversion from malignant to benign. The 30-day mortality was zero. Conclusions PITAC appears to be safe and feasible.

Objectives Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) is a minimally invasive cancer-directed therapy for patients with malignant pleural effusion (MPE) and/or pleural metastasis (PLM). PITAC is based on Pressurized IntraPeritoneal Aerosol Chemotherapy, which has proven to be safe and feasible. Since 2012, 47 PITACs have been published, and prospective data on feasibility, safety and potential local response are lacking. Methods The prospective, controlled, phase-I study is designed to treat MPE with PITAC. There are no data to support the estimated number of patients needed, but previous experience estimates the non-access rate to 20 %. Twenty eligible patients with MPE will receive two or more PITACs at four-week intervals. During video-assisted thoracoscopy, MPE and/or pleural lavage fluid is evacuated, and the extent of visible PLM is assessed. Pleural biopsies are collected, if possible, for histological response as per Thoracic Regression Grading Score (TRGS). Patients are screened for treatment-related intra- and postoperative complications. The primary outcome is the number of patients with Clavien-Dindo ≥3b or Common Terminology Criteria for Adverse Events≥4 within 30 days. Secondary objectives include PLM-score, TRGS and cytology, length of hospitalization, personnel safety, quality of life, and change in MPE volume. Results PITAC is expected to be safe and feasible for patients and personnel, and achieve positive results in the reduction of MPE volume. Conclusions The results may significantly impact the next clinical, technical, and scientific steps in the implementation of PITAC. Given the suboptimal treatment options for MPE and the seemingly promising results of PITAC, we find the implementation of PITAC ethically reasonable and sound.

Objectives Cancer cells can activate coagulation and inhibit fibrinolysis. The aim was to investigate the association between the burden of peritoneal metastases from colorectal cancer (PM-CRC) and biomarkers reflecting thrombin generation and fibrinolysis. Methods A cohort of 55 patients with PM-CRC scheduled for cytoreductive surgery. Patients were grouped by the peritoneal cancer index (PCI) assessed intraoperatively into limited PM-CRC (PCI≤15) and extensive PM-CRC (PCI>15). Blood samples were obtained before surgery. Thrombin generation was measured in vivo by thrombin-antithrombin complex (TAT) and prothrombin fragment 1+2 (F1+2), and ex vivo by the endogenous thrombin potential (ETP). Fibrinolysis was analyzed with fibrin clot lysis assay, fibrinogen, and D-dimer. Results Non-significantly decreased thrombin generation by F1+2 (p=0.72), TAT (p=0.32), and ETP (p=0.19) were observed in patients with extensive PM-CRC (n=9) compared with limited PM-CRC (n=46). Non-significantly prolonged 50 % clot lysis time were found in patients with extensive PM-CRC than in patients with limited PM-CRC. Conclusions Minor non-significant differences in thrombin generation and fibrinolysis were found between patients with extensive PM-CRC and limited PM-CRC. Thus, increased peritoneal metastatic burden from colorectal cancer does not seem to affect thrombin generation and fibrinolysis.