Pleura and Peritoneum最新文献

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: 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: Current therapies show limited efficacy against peritoneal metastases (PM) from pancreatic cancer. Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has emerged as a novel intraperitoneal drug delivery method. Recently, a dose-escalation study identified the safe dose of Nabpaclitaxel for PIPAC administration, an ideal intraperitoneal chemotherapy agent against pancreatic cancer. Combining systemic NabPaclitaxel-Gemcitabine with NabPaclitaxel-PIPAC may enhance disease control in pancreatic cancer patients with PM.

Methods: The Nab-PIPAC trial is a single-center, prospective, open-label, phase II study (ClinicalTrials.gov identifier: NCT05371223). Its primary goal is to evaluate the antitumor activity of the combined treatment based on Disease Control Rate (DCR) using RECISTv.1.1 criteria. Secondary objectives include feasibility, safety, pathological response, progression-free and overall survival, nutritional status, quality of life, pharmacokinetics of NabPaclitaxel-PIPAC, and PM molecular evolution via translational research. The treatment protocol consists of three courses, each with two cycles of intravenous NabPaclitaxel-Gemcitabine and one cycle of NabPaclitaxel-PIPAC, with standard metastatic pancreatic cancer doses for the former and 112.5 mg/m² for the latter. Sample size follows Simon's two-stage design: 12 patients in stage one and 26 in stage two (80 % power, 0.1 alpha).

Results: Partial results will be available after first stage enrollment.

Conclusions: This trial aims to determine the antitumor efficacy and safety of combining NabPaclitaxel-PIPAC with systemic NabPaclitaxel-Gemcitabine in pancreatic cancer patients with PM.

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.

Objectives: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface malignancies. However, surgical morbidity is high, and prediction of severe postoperative complications (SPC) is limited. We hypothesized that the changes in thromboelastogram (TEG) values following CRS could be associated with SPC.

Methods: We retrospectively analyzed a cohort of CRS and HIPEC patients who had TEG measured before and after CRS. Clinical and postoperative data were retrieved from a prospectively maintained database.

Results: Our 37-patient cohort was comprised of 24 men and 13 women with an age (median, [interquartile range, IQR]) 55 (47-65) years, of whom six had SPC. The ones with SPC did not differ from the others in age, sex, tumor histology or preoperative chemotherapy. The extent of surgery as measured by the peritoneal carcinomatosis index and the number of organs resected was comparable between SPC group vs. no SPC [9 (3-10.5) vs. 9 (5-14), p=1.0; 2 (0.75-2.25) vs. 2 (1-3), p=0.88, respectively]. The TEG parameters showed increased R- and K- time for the patients with SPC compared to those without (6 ± 3.89 vs. 4.05 ± 1.24, p=0.01; 1.65 ± 0.63 vs. 1.25 ± 0.4, p=0.03, respectively). The TEG values were significantly associated with SPC in the multivariable analysis (odds ratio=1.53, p=0.05).

Conclusions: TEG changes are associated with SPC. Intra-operative markers of SPC could guide intraoperative decisions, such as stool diversion and postoperative triage of patients to an appropriate level of care.

Objectives: Laparoscopic ultrasound (LUS) combines both laparoscopy and ultrasound imaging of the peritoneum liver and retroperitoneum. LUS has not been described in treatments with pressurized intraperitoneal aerosol chemotherapy (PIPAC). We present our experience with LUS in patients undergoing PIPAC.

Methods: Retrospective study of LUS findings from the prospective PIPAC-OPC2 trial. Main outcome was changes in overall treatment strategy due to LUS findings.

Results: PIPAC-OPC2 included 143 patients of which 33 patients were treated with electrostatic precipitation PIPAC. Nine patients were excluded due to primary non-access. During PIPAC 1, LUS was performed in 112 of 134 (84 %) PIPAC procedures and changed overall treatment strategy in one patient due to detection of multiple liver metastases unseen by baseline CT. During PIPAC 2 and 3 LUS was performed in 59 of 104 (57 %) and 42 of 78 (54 %) PIPAC procedures, respectively. Throughout PIPAC 1-3, LUS also detected pathological lymph nodes in 16 patients, and focal liver lesions in another four patients of uncertain origin. No further examinations were performed in these patients, and the overall treatment strategy was not changed according to the PIPAC-OPC2 protocol. One patient had a splenic capsule rupture related to the LUS itself. This was managed conservatively.

Conclusions: LUS may be safely performed during PIPAC. However, LUS has limited clinical impact in patients scheduled for PIPAC, and cannot be recommended as a routine procedure when performing PIPAC.

Objectives: Pleural effusion (PE) is the most frequent pulmonary complication of dasatinib, a tyrosine kinase inhibitor (TKI). Concurrent pericardial effusions have been reported in about one-third of the cases. In this study, we aimed to investigate ascites generation in chronic-phase chronic myeloid leukemia (CML-CP) patients developing PE under dasatinib.

Methods: We conducted a cross-sectional study to evaluate whether pericardial effusion and ascites accompany PE in CML-CP patients treated with dasatinib. For this purpose, consecutive patients with CML-CP who developed PE under dasatinib therapy have been evaluated with chest X-ray, transthoracic echocardiography, and abdominal ultrasonography.

Results: There were seven patients, and the median age was 50 years (range, 31-73 years). Most of patients were male (n=5). All patients received imatinib as first-line TKI. Six patients received dasatinib following imatinib failure in second line. The median duration from dasatinib initiation to PE generation was 58 months (range, 8-135 months). Consequently, four patients had grade 1 pericardial effusion, and no patient had ascites.

Conclusions: In our small study, dasatinib-related PE was associated with low-grade pericardial effusion but no ascites. There are hypothetical explanations of this phenomenon including the simultaneous activation/inhibition of kinases; however, more research needs to be performed on this topic.