Pleura and Peritoneum最新文献

Objectives: Biopsy morphology (surface/depth ratio) and sample processing might affect pharmacological measurements in peritoneal tissue.

Methods: This is an ex-vivo study on inverted bovine urinary bladders (IBUB). We compared cisplatin (CIS) and doxorubicin (DOX) concentration in 81 standardized transmural punch biopsies of different diameters (6 and 12 mm). Then, we assessed the effect of dabbing the peritoneal surface before analysis. After automatized tissue homogenization with ceramic beads followed by lyophilisation, DOX concentration was quantified by high-performance liquid chromatography (HPLC), CIS concentration by atomic absorption spectroscopy. Experiments were performed in triplicate; the analysis was blinded to the sample origin. Comparisons were performed using non-parametric tests.

Results: Concentrations are given in mean (CI 5-95%). Results were reproducible between experiments (for CIS p=0.783, for DOX p=0.235) and between different localizations within the IBUB (for CIS p=0.032, for DOX p=0.663). Biopsy diameter had an influence on CIS tissue concentration (6 mm biopsies: 23.2 (20.3-26.1), vs. 12 mm biopsies: 8.1 (7.2-9.2) ng/mg, p<0.001) but not on DOX: (0.46, 0.29-0.62) vs. 0.43 (0.33-0.54) ng/mg respectively, p=0.248). Dabbing the peritoneal surface reduced DOX tissue concentration (dry biopsies: 0.28 (0.12-0.43) vs. wet biopsies: 0.64 (0.35-0.93) ng/mg, p=0.025) but not CIS (23.5 (19.0-28.0) vs. 22.9 (18.9-26.9) ng/mg, respectively, p=0.735).

Conclusions: Measurements of drug concentration in peritoneal tissue can be influenced by the biopsy's surface/depth ratio and after drying the biopsy's surface. This influence can reach a factor three, depending on the drug tested. The biopsy technique and the pre-analytical sample preparation should be standardized to ensure reliable pharmacological measurements in peritoneal tissue.

Objectives: Peritoneal metastasis (PM) is commonly observed in patients with colorectal cancer (CRC). The outcome of these patients is poor, with an average survival of only six months without therapy, which requires a better understanding of PM biology and new treatment strategies.

Methods: We established and characterized a human ex vivo peritoneal model to investigate the mechanisms of peritoneal seeding and possible treatment options. For this, CRC cell lines and patient-derived tumor organoids were cultured together with human peritoneum to investigate the invasion of malignant cells and the effects of local chemotherapy.

Results: Fresh human peritoneum was cultured for up to three weeks in a stainless steel ring system, allowing for survival of all peritoneal structures. Peritoneal cell survival was documented by light microscopy and immunohistochemical staining. Further, immunohistological characterization of the tissue revealed CD3-positive T-lymphocytes and vimentin-positive fibroblasts within the peritoneum. In addition, extracellular matrix components (collagens, matrix metalloproteinases) were localized within the tissue. Coculture with CRC cell lines and patient-derived CRC organoids revealed that cancer cells grew on the peritoneum and migrated into the tissue. Coculture with CRC cells confirmed that hyperthermal treatment at 41 °C for 90 min significantly enhanced the intracellular entry of doxorubicin. Moreover, treatment with mitomycin C under hyperthermic conditions significantly reduced the amount of cancer cells within the peritoneum.

Conclusions: This human ex vivo peritoneal model provides a stringent and clinically relevant platform for the investigation of PM and for further elucidation of possible treatment options.

Objectives: Peritoneal metastases (PM) are relatively resistant to systemic chemotherapy, and data on histological response to therapy is rare. The aim of this study was to quantify the treatment response of PM after systemic chemotherapy.

Methods: Retrospective monocentric cohort study of 47 consecutive patients with PM from gastrointestinal origin undergoing surgery (cytoreduction: CRS + Hyperthermic IntraPEritoneal Chemotherapy [HIPEC] or Pressurized IntraPeritoneal Aerosol Chemotherapy [PIPAC]) after prior systemic chemotherapy from 1.2015 to 3.2019. Tumor response was assessed using the 4-scale Peritoneal Regression Grading System (PRGS) (4: vital tumor to 1: complete response).

Results: Patients had a median of 2 (range: 1-7) lines and 10 (3-39) cycles of prior systemic chemotherapy. A median of four biopsies (range: 3-8) was taken with a total of 196 analyzed specimens. Twenty-four biopsies (12%) showed no histological regression (PRGS4), while PRGS 3, two and one were diagnosed in 37 (19%), 39 (20%), and 69 (49%) specimens, respectively. A significant heterogeneity was found between peritoneal biopsies in 51% patients. PRGS correlated strongly with peritoneal spread (PCI, p<0.0001), and was improved in patients with more than nine cycles of systemic chemotherapy (p=0.04). Median survival was higher in patients with PRGS < 1.8 (Quartiles one and 2) than higher (Q3 and Q4), but the difference did not reach significance in this small cohort.

Conclusions: PRGS is an objective too to describe histological response of PM of GI origin after systemic chemotherapy. This response differs significantly between patients, allowing to distinguish between chemosensitive and chemoresistant tumors.

Objectives: Enhanced recovery after surgery (ERAS) protocols have been questioned in patients undergoing cytoreductive surgery (CRS) with/without hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies. This survey was performed to study clinicians' practice about ERAS in patients undergoing CRS-HIPEC.

Methods: An online survey, comprising 76 questions on elements of prehabilitation (n=11), preoperative (n=8), intraoperative (n=16) and postoperative (n=32) management, was conducted. The respondents included surgeons, anesthesiologists, and critical care specialists.

Results: The response rate was 66% (136/206 clinicians contacted). Ninety-one percent of respondents reported implementing ERAS practices. There was encouraging adherence to implement the prehabilitation (76-95%), preoperative (50-94%), and intraoperative (55-90%) ERAS practices. Mechanical bowel preparation was being used by 84.5%. Intra-abdominal drains usage was 94.7%, intercostal drains by 77.9% respondents. Nasogastric drainage was used by 84% of practitioners. The average hospital stay was 10 days as reported by 50% of respondents. A working protocol and ERAS checklist have been designed, based on the results of our study, following recent ERAS-CRS-HIPEC guidelines. This protocol will be prospectively validated.

Conclusions: Most respondents were implementing ERAS practices for patients undergoing CRS-HIPEC, though as an extrapolation of colorectal and gynecological guidelines. The adoption of postoperative practices was relatively low compared to other perioperative practices.

Objectives: Several trials have documented the favorable safety profile, and promising clinical results of pressurized intraperitoneal aerosol chemotherapy (PIPAC) directed treatment in different types of peritoneal malignancies. However, until the results of randomized trials are available, the quality of documentation and acceptance by the users may be improved through a worldwide registry. The International Society for the Study of Pleura and Peritoneum (www.ISSPP.org) facilitated this process by creating a dedicated focus group and providing the funding needed for the creation and implementation of an international database. This article describes the design and the journey of establishing this international database and the first, preliminary results from the ISSPP PIPAC online database.

Methods: In 2019 the ISSPP PIPAC Registry Group started to create a database with a minimal dataset relevant to many diseases and applicable in different framework conditions. The task was divided into three phases including design, testing, implementation, protocol, handbook, legal requirements, as well as registry rules and bylaws for the registry group.

Results: The ISSPP PIPAC online database has six key elements (patient, consent, treatment, complications, response evaluation and follow-up). Following design, testing and implementation the database was successfully launched in June 2020. Ten institutions reported on 459 PIPAC procedures in 181 patients during the first 6 months, and the recorded data were comparable to the present literature.

Conclusions: A new international multicenter PIPAC database has been developed, tested and implemented under the auspices of ISSPP. The database is accessible through the ISSPP website (www.ISSPP.org), and PIPAC institutions worldwide are highly encouraged to participate.

Objectives: Pleural effusion, defined as an abnormal accumulation of fluid in pleural space, can be of two types: transudative and exudative. The primary aim of the study was to assess the predictive accuracy of procalcitonin (PCT) and pentraxin-3 (PTX-3) in comparison to other biochemical markers such as C-reactive protein (CRP), and adenosine deaminase (ADA) in the differential diagnosis of pleural effusions.

Methods: A cross-sectional analytical study was conducted on patients with pleural effusion. Multiple comparisons and receiver-operating characteristics (ROC) analyses were made to evaluate the diagnostic significance of biochemical markers.

Results: Sixty-six patients with exudative pleural effusion classified as malignant, tuberculous, and parapneumonic effusions (malignant pleural effusion [MPE], tuberculous [TPE], and parapneumonic [PPE]) were included. Significant differences in pleural fluid levels in both PCT (p-value: 0.001) and PTX-3(p-value: 0.001), as well as serum levels of PCT (p-value: 0.001), were observed between the three groups. ROC analysis showed both PTX-3 and PCT having favorable discrimination ability with high sensitivity (≥90%) and specificity to predict PPE from TPE and MPE.

Conclusions: Evaluation of serum and pleural fluid PCT and levels of PTX-3 in the pleural fluid may be used as an early biomarker to differentiate the etiology of pleural effusion.

Objectives: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with postoperative gastroparesis and ileus. In 2015, our practice shifted from using percutaneous gastrostomy tubes (PGT), to nasogastric tubes (NGT) for prophylactic gastric decompression after CRS-HIPEC. This study aimed to compare these methods for length of stay (LOS) and associated complications.

Methods: Patients that underwent CRS-HIPEC for peritoneal metastases from colorectal cancer between 2014 and 2019 were included. Cases were grouped based on receiving NGT or PGT postoperatively. Multivariable linear regression determined the independent effect of decompression method on LOS, thereby adjusting for confounders.

Results: In total, 179 patients were included in the analyses. Median age was 64 years [IQR:54-71]. Altogether, 135 (75.4%) received a NGT and 44 (24.6%) received a PGT. Gastroparesis occurred significantly more often in the PGT group (18.2 vs. 7.4%, p=0.039). Median LOS was significantly shorter for patients with a NGT (15 [IQR:12-19] vs. 18.5 [IQR:17-25.5], p<0.001). PGT was independently associated with longer LOS in multivariable analysis (Beta=4.224 [95%CI 1.243-7.204]). There was no difference regarding aspiration, pneumonia and postoperative mortality between groups.

Conclusions: NGT should be preferred over PGT for gastric decompression after CRS-HIPEC as it is associated with fewer gastroparesis and shorter LOS.

Objectives: Platinum salts are commonly used in hyperthermic intraperitoneal chemotherapy (HIPEC) for digestive tract cancer treatment. During HIPEC with oxaliplatin for peritoneal metastases (PMs) treatment, the ovaries are directly exposed to the drug, questioning about ovarian resection and the potential impact of the drug on ovarian functionality, especially in young women of childbearing age. The goal of this work is to understand unwanted damages to the ovaries during HIPEC therapy by the determination of the concentration and distribution of platinum in ovaries in order to address its potential toxicity.

Methods: Mass spectrometry imaging techniques, matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP MS), were used to study the penetration of oxaliplatin in ovaries after HIPEC treatment.

Results: MALDI-MS allowed the localization of an oxaliplatin-derivative (m/z 456.2) at the periphery of the ovaries. The quantitative LA-ICP MS maps confirmed the localization of elemental platinum as well as in the central part of ovaries from patients who received a previous platinum salt-based chemotherapy.

Conclusions: LA-ICP MS images showed that platinum diffusion was extended in cases of previous systemic treatment, questioning about platinum derivatives gonado-toxicity when combining the two treatments.