Pleura and Peritoneum最新文献

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: 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.

Objectives: Treatment of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is still evolving. Conducting a randomized trial is challenging due to the high heterogeneity in the presentation of peritoneal disease and various surgical approaches. Biological research may facilitate more rapid translation of information into clinical practice. There is an emerging need for a preclinical model to improve HIPEC treatment protocols in terms of drug doses and treatment durations. The aim of the study is to design a tool that serves as an in vitro three-dimensional (3D) microfluidic peritoneal metastatic colorectal cancer model to test the efficacy of different HIPEC treatments.

Methods: We determined the effects of current therapy options using a 3D static disease model on human colon carcinoma cell lines (HCT 116) and transforming growth factor-β1 induced epithelial-to-mesenchymal transition (EMT) HCT 116 lines at 37 °C and 42 °C for 30, 60, and 120 min. We determined oxaliplatin's half maximal inhibitory concentrations in a 3D static culture by using viability assay. Clinical practices of HIPEC were applied in the developed model.

Results: EMT-induced HCT 116 cells were less sensitive to oxaliplatin treatment compared to non-induced cells. We observed increased cytotoxicity when increasing the temperature from 37 °C to 42 °C and extending the treatment duration from 30 to 120 min. We found that 200 mg/m² oxaliplatin administered for 120 min is the most effective HIPEC treatment option within the framework of clinic applications.

Conclusions: The tool map provide insights into creating more realistic pre-clinical tools that could be used for a patient-based drug screening.