Pleura and Peritoneum最新文献

Objectives: Ovarian cancer (OC) often presents with peritoneal metastases (PM) which contribute significantly to morbidity and treatment resistance. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) has emerged as a promising modality for locoregional drug delivery in peritoneal surface malignancies. Historically, combined intraperitoneal (IP) and intravenous (IV) cisplatin and paclitaxel regimens have demonstrated activity in first-line OC treatment. PIPAC nab-paclitaxel and cisplatin with systemic nab-paclitaxel holds promise as a safe and effective therapy, but has not been explored in OC.

Methods: This ongoing, dose de-escalation, single-arm phase I study evaluates triplet bidirectional chemotherapy with a safety lead-in (NCT04329494). The study evaluates the safety and tolerability of a 28-day cycle of Day 1 PIPAC nab-paclitaxel 90 mg/m² and cisplatin 15 mg/m² in combination with Days 8 and 15 IV nab-paclitaxel 100 mg/m² for three cycles in recurrent OC patients with unresectable PM.

Results: Enrollment is ongoing at U.S. academic centers. The primary endpoints are dose-limiting toxicities and adverse events. Secondary endpoints include radiographic (RECIST v1.1), histologic, and surgical response, progression-free and overall survival, and post-operative complications.

Conclusions: This study investigates the safety, feasibility, and preliminary activity of the combination of PIPAC and systemic IV chemotherapy in recurrent OC patients to determine efficacy and safety for a future Phase II trial.

Objectives: Malignant pleural effusion is a common evolution of various cancers and is associated with poor prognosis and quality of life. Currently, the surgical approach is mainly palliative, involving videothoracoscopic talc pleurodesis or the insertion of indwelling pleural catheters. No surgical options with a curative intent are validated for this indication. The aim of our study was to evaluate a score for assessing resectability in pleural carcinomatosis.

Methods: 122 consecutive patients with recurrent symptomatic pleural effusion, referred to our thoracic surgery department for a surgical exploration of the pleura, were prospectively included. Each patient underwent a detailed description of videothoracoscopic findings, which were summarized in our pleural carcinomatosis score. Resectability was then discussed in our surgical staff meeting.

Results: Eighty patients (65.6 %) were diagnosed with metastatic pleural spread, while 42 patients were diagnosed with benign pleural disease (34.4 %). Patients diagnosed with benign pleural effusion had a median score of 2, and 29 patients (69 %) were considered resectable. Patients diagnosed with malignant pleural effusion had a median score of 11, and only 13 patients (16.2 %) were considered resectable. Those deemed resectable had a median score of 5. The threshold for resectability in our score was set at 6.

Conclusions: The meticulous exploration of the pleura and calculation of the pleural carcinomatosis score could aid in selecting patients for curative-intent surgery. Patients with a score equal to or less than 6 should be discussed in a multidisciplinary tumor board where the possibility of surgery is considered.

Objectives: To evaluate current postoperative management strategies for incidentally discovered, completely resected low-grade appendiceal mucinous neoplasms (LAMNs) within the French RENAPE network and to assess the need for a new national consensus.

Methods: A national survey was conducted among RENAPE expert centers using a structured questionnaire based on standardized postoperative risk scenarios. Survey items addressed surveillance strategies, indications for reoperation, and use of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

Results: Ninety-one percent of centers responded. All reported systematic multidisciplinary discussion, centralized pathology and imaging review, standardized imaging, and tumor marker assessment. Marked heterogeneity was observed. For low-risk patients (R0 resection, no perforation, no extra-appendiceal mucin), 50 % recommended no follow-up and 50 % proposed long-term MRI surveillance. In intermediate-risk cases (limited perforation or adjacent mucin), 80 % favored MRI follow-up, while 20 % recommended diagnostic laparoscopy or prophylactic CRS-HIPEC. In high-risk scenarios with radiologic suspicion of implants, 60% proposed early CRS-HIPEC, whereas others preferred laparoscopic assessment or surveillance.

Conclusions: This survey highlights wide variation in postoperative strategies for LAMNs within RENAPE, especially in intermediate-risk cases. While consensus exists on centralized review and imaging, significant evidence gaps persist regarding prophylactic HIPEC. These findings underscore the need for harmonized, evidence-based protocols and prospective data collection.

Objectives: Pseudomyxoma peritonei (PMP) is a rare, slow-growing cancer with few efficacious treatment options in unresectable cases. Mutations in the KRAS and GNAS oncogenes are common, but the reported frequencies vary greatly, most likely because of low tumor cellularity in peritoneal tumor samples. With treatments targeting these mutations becoming increasingly available, reliable detection of mutations is essential.

Methods: The frequency of KRAS and GNAS mutations was analyzed in tumor samples from 167 patients with verified PMP using targeted DNA sequencing and/or droplet digital polymerase chain reaction. When analysis of fresh-frozen peritoneal tumor samples did not reveal mutations, macrodissected formalin-fixed samples were analyzed.

Results: Mutations in cancer-related genes were detected in 98 % of the analyzed samples, with KRAS and GNAS mutated in 148 (89 %) and 139 (83 %) cases, respectively. In 48 % of the analyzed cases, the mutational diagnosis was based on primary tumor samples.

Conclusions: High frequencies of KRAS and GNAS mutations support the proposed role as driver mutations and as potential therapy targets. The primary tumor may serve as an alternative source of tumor material, increasing the likelihood of detecting targetable mutations. Combined with highly sensitive analytical methods, this approach facilitates selection of patients for novel targeted therapeutic strategies.

Objectives: The effects of preoperative chemotherapy have been poorly studied in colorectal cancer with peritoneal metastases (CRC-PM). This study evaluated preoperative chemotherapy from the first multi-disciplinary team meeting (MDT) decision, focusing on the response rates, surgical outcomes, and survival.

Methods: This retrospective cohort study analyzed consecutive patients with resectable or potentially resectable CRC-PM evaluated at Uppsala University Hospital's peritoneal-MDT between March 2019 and December 2023. Kaplan-Meier curves and Cox-regression analyses were used for survival analysis.

Results: Of 179 patients, 81 underwent upfront surgery; 52 received doublet chemotherapy and 46 received doublet with targeted therapy. Targeted group showed a 52 % overall response rate vs. 36 % for doublet group (p=0.14), with patients selected for CRS and HIPEC at a 52 % vs. 31 % rate, respectively, p=0.086. The median overall survival was superior in the targeted group than in the doublet group (intention-to-treat with all patients included): 21 (95 %CI: 18-35) vs. 17 (95 %CI: 14-22) months (p=0.027). The VEGF-targeted therapy outperformed EGFR-targeted therapy: 32 (95 %CI: 21-Not reached) vs. 15 (95 %CI: 11-40) months (p=0.042).

Conclusions: Preoperative chemotherapy with targeted antibodies improves overall survival in CRC-PM in patients that are not candidates for upfront CRS and HIPEC. Bevacizumab is associated with improvement over EGFR targeted treatment in a subgroup analysis.

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative intraperitoneal drug delivery technique utilizing a nebulizer to aerosolize liquid chemotherapy agents under pressure, distributing them evenly throughout the peritoneal cavity to achieve therapeutic effects. As increasing clinical evidence supports the safety and efficacy of PIPAC as a promising treatment for peritoneal metastasis, optimizing nebulizer technology to enhance treatment outcomes has garnered significant research interest.

Content: Following initial investigations into the internal structure, mechanical properties, and optimization parameters of the original PIPAC nebulizer, researchers worldwide have focused on refining nebulizer design and exploring innovative applications of aerosolization devices, resulting in the development of several clinically applicable nebulizers with distinct characteristics.

Summary: This review aims to provide a comprehensive examination of the global advancements in PIPAC nebulizer development, the nebulizer alternative devices, evaluation parameters and methods, as well as future research directions, aiming to inform the development, optimization, and application of novel nebulizers for PIPAC, thereby contributing to the advancement of this promising therapeutic approach.

Outlook: Current methods for evaluating nebulizer performance are continually being refined, and the integration of nebulizers with other physical modalities holds great promise for further improving PIPAC outcomes.

Objectives: Peritoneal mesothelioma (PM) shares features with genitourinary (GU) malignancies, including histologic appearance, embryologic origin and genetic predispositions. However, data on their co-occurrence are limited. The study presents a case series of PM patients with associated GU malignancies and explores outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

Methods: A prospectively maintained CRS-HIPEC database from a tertiary referral center (2011-2024) was reviewed. Demographics, tumor characteristics and outcomes were compared between PM patients with and without GU malignancies (including gynecologic and urologic cancers).

Results: Among 237 CRS-HIPEC patients, 8/17 patients with PM were found to have another GU malignancy (median age 52.8, 62.5 % male). This included renal cell carcinoma, prostate cancer, ovarian tumors and cervical carcinoma. Most GU malignancies were diagnosed before PM (5/8), two were diagnosed post-CRS-HIPEC, and one synchronously. Three patients reported asbestos exposure; two had BAP1 mutations. Compared to those without GU malignancies, affected patients tended to have higher PCI (19.8 vs. 14.3) and poorer 3-year survival (62.5 vs. 100 %).

Conclusions: GU malignancy is common among PM patients undergoing CRS-HIPEC and could represent a higher-risk subgroup. These findings raise the hypothesis of a potential association between PM and GU malignancy. Shared origins, oncogenesis of similar cell types, environmental exposures or genetic predispositions may contribute and warrant further investigation.

Objectives: Pseudomyxoma peritonei (PMP) is a rare peritoneal malignancy. BromAc ^® is a novel therapeutic agent which has been developed to dissolve and facilitate the drainage of mucin as a palliative treatment for PMP; however, its effect is significantly reduced in patients with hard mucin. This study aimed to assess whether combining collagenase or cysteamine with BromAc ^® would be more effective in dissolving hard mucin.

Methods: This preclinical human in vitro study examined the effect of adding collagenase to BromAc ^® on hard mucin samples when incubated at 37 °C over 24 h. The effect of cysteamine alone and in combination with collagenase and BromAc ^® was also examined as a supplementary arm of this study. Five experiments were conducted with appropriate controls. Human hard mucin samples were sliced into equal fractions using a sterile surgical scalpel, weighed and noted. The leftover solid mucin was weighed at 0, 1, 3, 5, and 24 h post-treatment.

Results: At 24 h post-treatment, all combinations with collagenase demonstrated almost 100 % dissolution of hard mucin. At 3 and 5 h post-treatment, only BromAc ^® with collagenase at 250 μg/mL was found to be superior to BromAc ^® alone. Combinations with cysteamine were not found to be effective.

Conclusions: This study provides promising evidence of the efficacy and synergistic effect of combining BromAc ^® with collagenase to dissolve hard mucin. Further preclinical and clinical research should be undertaken to assess its safety and efficacy in the clinical setting.

Objectives: Complicated pleural infections present significant challenges. Predominant causative microorganisms include the Streptococcus anginosus group (SAG) and Klebsiella pneumoniae (KP). However, limited data are available on the risk factors and outcomes associated with SAG-related pleural infection compared to KP-related pleural infection.

Methods: This retrospective study was conducted in patients who underwent pleural drainage due to complicated pleural infection at Kyungpook National University Hospital in South Korea between January 2011 and December 2023. Clinical characteristics, drug resistance profiles, and outcomes were compared between patients with SAG-related and KP-related pleural infections.

Results: A total of 432 patients were assessed. Among them, 161 (37 %) had positive pleural fluid cultures, with SAG (n=68, 42 %) and KP (n=34, 21 %) being the predominant pathogens. Thus, 102 patients with complicated pleural infection caused by SAG or KP were analyzed. SAG cases were associated with higher rates of chronic neurologic disease, lower rates of diabetes mellitus, prolonged symptom duration, elevated white blood cell counts, and positive gram stains on pleural fluid compared to KP cases. There were no significant differences observed between the two groups regarding radiological findings. SAG strains showed resistance rates exceeding 20 % to penicillin, erythromycin, tetracycline, and clindamycin, while remaining largely susceptible to commonly used third-generation cephalosporins, ampicillin, and fluoroquinolones. The in-hospital mortality rates were approximately 10 %, consistent across both groups.

Conclusions: SAG-related pleural infections showed distinct clinical features, including more frequent chronic neurologic disease, but in-hospital mortality was comparable to that of KP-related infections.