Pleura and Peritoneum最新文献

Objectives: Despite the introduction of multimodal treatment regimens, the prognosis of gastric cancer peritoneal metastasis (GCPM) remains poor. To establish efficient therapies, a deeper understanding of pathophysiological mechanisms in the development of GCPM is necessary and this requires adequate functional models. Therefore, we established a three-dimensional model to study tumor adhesion, invasion and growth.

Methods: A co-culture of peritoneal mesothelial cells with fibroblasts and collagen I was cultivated to further seed human gastric cancer cell lines on the surface. Different imaging techniques (optical microscopy, immunohistochemistry, scanning (SEM) and transmission (TEM) electron microscopy) served as tools to proof the sustainability of the model.

Results: We demonstrated the feasibility of creating a robust GCPM model. We showed that the model is reproducible under various conditions (6-, 12-, and 24-wells) and pre-analytical processing is possible. The imaging was feasible and allowed the comparison of morphological changes on the GCPM model to normal human peritoneum.

Conclusions: We established a reproducible and robust organotypic model of GCPM which can be used to generate deeper knowledge on the pathophysiology of GCPM and might serve as a platform for testing different chemotherapy schemes in order to establish a personalized treatment for patients with GCPM.

Objectives: The prognosis of patients with peritoneal metastases (PM) is poor, and these patients have a brief overall survival. Most patients with advanced PM receive palliative therapy to maintain their quality of life. In our current study, we investigated whether patient-specific 3D-tissue slices from patients with PM subjected to pressurized intraperitoneal aerosol chemotherapy could be cultured in vitro.

Methods: Biopsies from gastric cancer patients with PM were characterized for cytokeratin-positive tumor cells and the proliferation marker Ki-67. Biopsies from seven patients were cut to 350 µM thick slices in a standardized manner, cultured with 10 µM 5-fluorouracil, doxorubicin, cisplatin, oxaliplatin, or irinotecan for 96 h, and then examined histopathologically and via immunohistochemistry for persistent cytokeratin and Ki-67 expression.

Results: In vitro cultured slices revealed a similar morphology to un-cultured specimens, and Ki-67-positive tumor cell areas were present after 96 h. The total amount of tumor cells per slice was determined by pan-cytokeratin staining. In the doxorubicin-treated slices, the cytokeratin-positive tumor cell fraction and proliferative (Ki-67pos) cells were decreased. Patient-specific 3D-tissue-slice cultures from peritoneal biopsies were cultured in vitro for up to 4 days.

Conclusions: Potentially, these cultures are a reliable model to evaluate the chemosensitivity of patients with PM. Further investigation is needed to match the chemosensitivity with the clinical course of these patients.

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.