Pleura and Peritoneum最新文献

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.

Objectives: Peritoneal regression grade score (PRGS) has emerged a scoring system designed to measure the extent of residual disease following systemic or intraperitoneal therapies in patients with carcinomatosis. Higher (3-4) PRG-Scores match with a mediocre treatment response and prognosis. Conversely, lower grades (1-2) response are linked to significantly longer overall and progression-free survival periods. This study explores the utility of PRGS in assessing prognosis and optimizing therapeutic strategies for patients with peritoneal metastasis secondary to gastric malignancy.

Methods: This is a prospective cohort study, including patients with gastric cancer and peritoneal metastasis undergoing chemotherapy with intent for subsequent cytoreductive surgery. The primary endpoint of the study is to assess the pathological response of peritoneal involvement to primary chemotherapy according to the PRGS. Secondary objectives are to correlate PRGS with some clinical, pathological and molecular features (MMR, PDL1, CPS, HER2) as well as with other clinical and biochemical markers related to chemotherapy response.

Results: This protocol summarizes the current scientific evidence regarding the effectiveness of the PRGS in assessing peritoneal response to targeted therapies. It further hypothesizes its potential utility in evaluating the effects of systemic therapies for gastric cancer with peritoneal metastases, while also defining inclusion and exclusion criteria and outlining a flowchart for its implementation.

Conclusions: Our final endpoint is to expand PRGS applications to curative settings and identify factors such as tumor biology and chemotherapy regimens that may guide patient selection for adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer with peritoneal metastasis.

Objectives: Non-mucinous appendiceal neoplasms (NMAN) are rare. The role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal dissemination from NMAN is poorly defined. We hypothesise that histology impacts survival and compared the disease characteristics and short- and long-term outcomes of mucinous and non-mucinous appendiceal neoplasms treated with CRS/HIPEC.

Methods: We retrospectively reviewed a prospective database of 228 patients with peritoneal disease from appendiceal primaries proceeding to CRS/HIPEC from 01/01/2008 to 30/06/2022 at a tertiary referral centre in New Zealand.

Results: There were 209 mucinous appendiceal neoplasms (MANs) and 19 NMANs. NMANs were more likely to metastasise to lymph nodes (p<0.001) and be treated with systemic chemotherapy (p<0.001) than MANs. Surgery for NMAN was more likely to involve small bowel resection (p<0.001) and less likely to achieve complete cytoreduction (p<0.001). Short-term outcomes were similar between MAN and NMAN. CRS/HIPEC for NMAN had a major complication rate of 15.3 % and no perioperative mortality. Extraperitoneal recurrence, including pleural and systemic recurrence, was more likely to occur in NMAN than all grades of MAN. The median overall survival was not reached in MAN and 16.0 months in NMAN. High PCI, ECOG, and tumour grade were associated with poor survival in NMAN.

Conclusions: The prognosis following CRS/HIPEC for NMAN is poor. Patients with NMAN need to be judiciously selected for CRS/HIPEC.

Objectives: In 2020, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) reached stage 2b of the IDEAL framework and a prospective international PIPAC database was launched in June 2020 by the International Society for the Study of the Pleura and Peritoneum (ISSPP). The ISSPP PIPAC database consists of six key elements, which are reported in an annual report. The ISSPP Registry Group decided to investigate data completeness within the ISSPP PIPAC Database.

Methods: Retrospective analysis of data completeness in the six key elements was performed between October 1st and 14th, 2024. This was complemented by an in-depth analysis of missing data in Response Evaluation, Complications, and Follow-up.

Results: Thirty centers, 950 patients, and 2777 PIPAC procedures were registered in the ISSPP database by October 2024. Sixteen of the 30 centers had included patients. Incomplete data were observed in four of the six key elements. Most centers (7/16) had incomplete data in Complications, followed by Response evaluation (5/16), and Follow-up (2/16). In depth analysis showed that, e.g., for complications, the date and type of the complication was registered in 88 and 89 %, respectively. Incomplete data in Response evaluation occurred mainly in the small group of patients evaluated by nonperitoneal regression grading score (non-PRGS, n=316), where no scoring was provided in 211 patients (72 %). Follow-up data, such as date of death or reasons for stopping PIPAC, were provided for 86 and 85 % of patients.

Conclusions: Overall data completeness of the ISSPP PIPAC Database was considered satisfactory at the present state, and the ISSPP Registry Group has launched several initiatives to further improve data completeness and quality, to provide solid data sets for future annual reports and other research.

Objectives: Cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC) requiring diaphragmatic stripping or resection may predispose to pleuropulmonary recurrence. This review was to assess the rates of pleuropulmonary recurrence after CRS/HIPEC for patients who had high-grade appendiceal neoplasm and meosthelioma.

Methods: A retrospective review (September 1996-November 2021) at a single tertiary center identified 716 patients who underwent CRS/HIPEC with diaphragmatic intervention; 203 had high-grade appendiceal neoplasms and 63 had mesothelioma. Radiologic or pathologic evidence of pleuropulmonary recurrence was recorded. Time from CRS/HIPEC to chest recurrence was analyzed using Kaplan-Meier methods.

Results: Twenty patients (12 appendiceal; 8 mesothelioma) developed pleuropulmonary recurrence. In the appendiceal cohort (mean age 51.5 years; median PCI 30), all 12 underwent bilateral diaphragm intervention (four with full-thickness resection) with CCR 0-1. Time to chest recurrence ranged from 0.3 to 82.8 months; half experienced early respiratory complications (e.g., pleural effusion, pneumothorax). In the mesothelioma cohort (mean age 44.9 years; median PCI 22.1), seven had bilateral stripping (two with resection) and one had unilateral stripping; CCR was 0-1. Recurrence occurred between 8.0 and 85.4 months (median ∼31.4 months); half had early respiratory compromise. No significant associations were observed between PCI, CCR, or extent of diaphragmatic intervention and recurrence risk, although ICU stay and CCR weakly correlated with recurrence in mesothelioma.

Conclusions: Pleuropulmonary recurrence following CRS/HIPEC with diaphragm intervention is rare (2.7 %), with early recurrences suggesting occult thoracic involvement. Bilateral diaphragm manipulation was common among those with recurrence.

Objectives: In 2020, the International Society for the Study of the Pleura and Peritoneum (ISSPP) launched a database monitoring real-world data on Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)-directed therapy in patients with peritoneal metastases (PM). This study covers data from the third annual report on the ISSPP PIPAC database.

Methods: Systematic analysis of all data reported to the ISSPP PIPAC database between June 15th, 2020, and November 1st, 2024. We hypothesize that ISSPP PIPAC data align with existing literature.

Results: Seventeen PIPAC centers reported 3224 PIPAC treatments in 1126 patients with PM (median number of treatments 2, range 1-33). The median peritoneal cancer index (PCI) at PIPAC 1 was 19 and remained unchanged during subsequent treatments. The number of patients with >500 mL ascites significantly decreased from the first three PIPAC treatments to PIPAC 4+ (p<0.01). Major complications (Dindo-Clavien ≥3b) occurred in 0.7 % of the treatments, while Common. Terminology Criteria for Adverse Events (CTCAE) grades ≥3 were reported in 5.2 %. Peritoneal regression grading score (PRGS) was performed in 2306 (72 %) of the treatments. At PIPAC 1, 2, and 3, complete or major response (mean PRGS ≤2) was achieved in 57 %, 72 %, and 75 % of the patients, respectively. Median overall survival from PIPAC 1 was 12.5 months. Patients with complete/major response (mean PRGS ≤2) at PIPAC 1-3 had a longer overall survival compared to patients with minimal/no response (mean PRGS >2).

Conclusions: This study from the ISSPP PIPAC database provides substantial real-world data demonstrating the feasibility, safety, and potential effect of PIPAC-directed therapy in patients with PM.