-
The Lancet. Respiratory Medicine Jun 2024Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone.
METHODS
MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants.
FINDINGS
Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group.
INTERPRETATION
Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone.
FUNDING
National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).
Topics: Humans; Female; Male; Pleural Neoplasms; Middle Aged; Aged; Mesothelioma; Treatment Outcome; United Kingdom; Pleura; Mesothelioma, Malignant; Combined Modality Therapy; Adult; Antineoplastic Combined Chemotherapy Protocols; Lung Neoplasms
PubMed: 38740044
DOI: 10.1016/S2213-2600(24)00119-X -
Respiratory Medicine Mar 2017Medical thoracoscopy is an effective and safe procedure for diagnosing pleural effusions of undetermined causes. But there are still a part of patients with pleural...
BACKGROUND
Medical thoracoscopy is an effective and safe procedure for diagnosing pleural effusions of undetermined causes. But there are still a part of patients with pleural effusions were diagnosed as nonspecific pleurisy when no specific biopsy results were found after undergoing thoracoscopic biopsy. The long-term outcome of these patients is unclear, and anxieties about undiagnosed malignancy persist.
METHODS
Between July 2005 and June 2014, medical thoracoscopy using the semi-rigid instrument was performed and pleural biopsy was taken in 833 patients with pleural effusions. Fifty-two patients diagnosed with nonspecific pleurisy with available follow-up data were included in the present study and their medical records were reviewed.
RESULTS
Fifty-two patients (31 men and 21 women) were included. Mean follow up was 35.5 ± 40.9 months (range, 1-143 months). No specific diagnosis was established in 21 (40.4%) of the patients. Eight of 52 patients with nonspecific pleurisy (15.4%) were subsequently diagnosed with pleural malignancies. 23 of 52 patients (44.2%) were diagnosed as benign diseases. The recurrence of pleural effusion during followed-up and pleural nodules or plaques found in medical thoracoscopy was associated with malignant disease.
CONCLUSION
Patients with nonspecific pleurisy after medical thoracoscopy should be closely monitored, especially in those patients with the recurrence of pleural effusion during followed-up, pleural nodules or plaques found in medical thoracoscopy. One year of clinical follow-up for patients found to have nonspecific pleurisy is likely sufficient.
Topics: Aged; Biopsy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Patient Outcome Assessment; Pleura; Pleural Effusion; Pleural Effusion, Malignant; Pleural Neoplasms; Pleurisy; Recurrence; Thoracoscopy
PubMed: 28284315
DOI: 10.1016/j.rmed.2017.01.005 -
Scientific Reports Nov 2017Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics...
Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206. Differential expression analysis of transcriptomes from four paired samples before and after treatment identified 230 treatment-specific responsive genes in pleural macrophages. Functional analysis identified interferon-related pathway to be the most responsive genes and further confirmed macrophage polarization to M2-like phenotype. We further demonstrate that expression of a significant fraction of responsive genes was modulated directly by antibiotics in pleural macrophages in vitro. Our results conclude that pleural macrophages polarize from M1-like to M2-like phenotype within a mean of 3.5 days post antibiotics treatment, which is dependent on both pleural cytokine environment and direct modulatory effects of antibiotics. The treatment-specific genes could be used to study the roles of pleural macrophages in the pathogenesis of tuberculous pleuritis and to monitor the response to antibiotics treatment.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biomarkers; Cell Polarity; Cytokines; Down-Regulation; Female; Humans; Macrophage Activation; Macrophages; Male; Middle Aged; Pleura; Tuberculosis, Pleural; Young Adult
PubMed: 29101376
DOI: 10.1038/s41598-017-14808-9 -
Thorax Apr 1994
Review
Topics: Adult; Developing Countries; Female; HIV Infections; Humans; Male; Respiratory Tract Infections; Tropical Medicine
PubMed: 8202911
DOI: 10.1136/thx.49.4.370 -
Hawai'i Journal of Medicine & Public... Sep 2015Toothpicks are commonly used household items that rarely cause serious injury or infection. Toothpick-related injuries often occur due to ingestion with subsequent...
Toothpicks are commonly used household items that rarely cause serious injury or infection. Toothpick-related injuries often occur due to ingestion with subsequent trauma/infection at distal sites within the gastrointestinal tract; however, cardiovascular, pleural, and soft tissue infections have been reported. Eikenella corrodens is a gram-negative, facultative anaerobic bacillus found in oral flora associated with bite wound infections. A few case reports describe E. corrodens osteomyelitis from toothpick puncture wounds. We report a case of foot cellulitis and abscess in an elderly diabetic after toothpick puncture injury that was unresponsive to empiric antibiotics. Wound cultures grew E. corrodens and rare Peptostreptococcus species. E. corrodens is resistant to first-generation cephalosporins, macrolides, aminoglycosides, clindamycin, and metronidazole. This case highlights the insidious nature of E. corrodens infections and the need to tailor empiric antibiotics for skin and soft tissue infections based on the mechanism of injury. In addition, this case stresses the importance of protective footwear in diabetics and serves as a cautionary tale regarding the use of seemingly innocuous toothpicks.
Topics: Abscess; Aged; Cellulitis; Eikenella corrodens; Female; Foot Diseases; Gram-Negative Bacterial Infections; Humans; Mouth; Wounds, Penetrating
PubMed: 26793413
DOI: No ID Found -
PloS One 2013Heat shock protein 70 (HSP70) has been implicated in infection-related processes and has been found in body fluids during infection. This study aimed to determine...
Heat shock protein 70 (HSP70) has been implicated in infection-related processes and has been found in body fluids during infection. This study aimed to determine whether pleural mesothelial cells release HSP70 in response to bacterial infection in vitro and in mouse models of serosal infection. In addition, the in vitro cytokine effects of the HSP70 isoform, Hsp72, on mesothelial cells were examined. Further, Hsp72 was measured in human pleural effusions and levels compared between non-infectious and infectious patients to determine the diagnostic accuracy of pleural fluid Hsp72 compared to traditional pleural fluid parameters. We showed that mesothelial release of Hsp72 was significantly raised when cells were treated with live and heat-killed Streptococcus pneumoniae. In mice, intraperitoneal injection of S. pneumoniae stimulated a 2-fold increase in Hsp72 levels in peritoneal lavage (p<0.01). Extracellular Hsp72 did not induce or inhibit mediator release from cultured mesothelial cells. Hsp72 levels were significantly higher in effusions of infectious origin compared to non-infectious effusions (p<0.05). The data establish that pleural mesothelial cells can release Hsp72 in response to bacterial infection and levels are raised in infectious pleural effusions. The biological role of HSP70 in pleural infection warrants exploration.
Topics: Adult; Aged; Aged, 80 and over; Animals; Cell Line; Cytokines; Epithelial Cells; Epithelium; Extracellular Space; Female; HSP72 Heat-Shock Proteins; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Middle Aged; Peritoneal Lavage; Pleura; Pleural Effusion; Streptococcal Infections; Streptococcus pneumoniae
PubMed: 23704948
DOI: 10.1371/journal.pone.0063873 -
PloS One 2021Evacuation of infected fluid in pleural infections is essential. To date, the use of an intrapleural fibrinolytic agent such as urokinase and DNase has not yet been... (Comparative Study)
Comparative Study
INTRODUCTION
Evacuation of infected fluid in pleural infections is essential. To date, the use of an intrapleural fibrinolytic agent such as urokinase and DNase has not yet been assessed in infections managed by repeated therapeutic thoracentesis (RTT).
METHODS
We performed a retrospective comparative study of two successive cohorts of consecutive patients with pleural infections from 2001 to 2018. Between 2001 and 2010, patients had RTT with intrapleural urokinase (RTT-U). After 2011, patients received intrapleural urokinase and DNase with RTT (RTT-UD). Data were collected through a standardized questionnaire.
RESULTS
One hundred and thirty-three patients were included: 93 were men and the mean age was 59 years (standard deviation 17.2). Eighty-one patients were treated with a combination of intrapleural urokinase and DNase, and 52 were treated with intrapleural urokinase only. In the RTT-UD, RTT failure occurred in 14 patients (17%) compared to 10 (19%) in the RTT-U group (P = 0.82). There was no difference between the two groups in intensive care unit admission, surgical referrals or in-hospital mortality. RTT-UD was associated with faster time to apyrexia (aOR = 0.51, 95%CI [0.37-0.72]), a reduced length of hospital stay (aOR = 0.61, 95%CI [0.52-0.73]) and a higher volume of total pleural fluid retrieved (aOR = 1.38, 95%CI [1.02-1.88]). Complications were rare with only one hemothorax in the RTT-UD group and no pneumothorax requiring drainage in either group.
CONCLUSION
Compared to urokinase only, intrapleural use of urokinase and DNase in RTT was associated with quicker defervescence, shorter hospital stay and increased volumes of pleural fluid drained. Randomized controlled trials evaluating urokinase and DNase with RTT technique would be required to confirm these results.
Topics: Adult; Aged; Deoxyribonucleases; Disease-Free Survival; Drainage; Empyema, Pleural; Female; Humans; Male; Middle Aged; Pleura; Pleural Diseases; Pleural Effusion; Pneumothorax; Retrospective Studies; Surveys and Questionnaires; Thoracentesis; Urokinase-Type Plasminogen Activator
PubMed: 34547022
DOI: 10.1371/journal.pone.0257339 -
Respiratory Medicine Sep 2015Differentiating tuberculous pleural effusion from other lymphocytic pleural effusions is often challenging. This retrospective study aimed to assess the efficacy and...
BACKGROUND
Differentiating tuberculous pleural effusion from other lymphocytic pleural effusions is often challenging. This retrospective study aimed to assess the efficacy and safety of medical thoracoscopy in patients with suspected tuberculous pleural effusion.
METHODS
Between July 2005 and June 2014, patients with pleural effusions of unknown etiologies underwent medical thoracoscopy in our institute after less invasive means of diagnosis had failed. Demographic, radiographic, procedural, and histological data of patients with tuberculous pleural effusion were analyzed.
RESULTS
During this 9-year study, 333 of 833 patients with pleural effusion were confirmed to have tuberculous pleurisy. Under thoracoscopy, we observed pleural nodules in 69.4%, pleural adhesion in 66.7%, hyperemia in 60.7%, plaque-like lesions in 6.0%, ulceration in 1.5% of patients with tuberculous pleurisy. Pleural biopsy revealed the presence of Mycobacterium tuberculosis in the pleural tissue or/and demonstration of caseating granulomas in 330 (99.1%) patients. No serious adverse events were recorded, and the most common minor complication was transient chest pain (43.2%) from the indwelling chest tube.
CONCLUSIONS
Our data showed that medical thoracoscopy is a simple procedure with high diagnostic yield and excellent safety for the diagnosis of tuberculous pleural effusion.
Topics: Adult; Aged; Biopsy; Female; Humans; Male; Middle Aged; Pleura; Pleural Effusion; Retrospective Studies; Thoracoscopy; Tomography, X-Ray Computed; Tuberculosis, Pleural
PubMed: 26166016
DOI: 10.1016/j.rmed.2015.06.008 -
Journal of Korean Medical Science Jan 2021The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain...
The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain necrosis. Compared with other organs, the etiological distribution and morphological patterns of pleural epithelioid granulomas have rarely been investigated. We evaluated the final etiologies and morphological patterns of pleural epithelioid granulomatous inflammation in a tuberculosis (TB)-prevalent country. Of 83 patients with pleural granulomas, 50 (60.2%) had confirmed TB pleurisy (TB-P) and 29 (34.9%) had probable TB-P. Four patients (4.8%) with non-TB-P were diagnosed. With the exception of microbiological results, there was no significant difference in clinical characteristics and granuloma patterns between the confirmed TB-P and non-TB-P groups, or between patients with confirmed and probable TB-Ps. These findings suggest that most pleural granulomatous inflammation (95.2%) was attributable to TB-P in TB-endemic areas and that the granuloma patterns contributed little to the prediction of final diagnosis compared with other organs.
Topics: Adenosine Deaminase; Adult; Algorithms; DNA, Bacterial; Female; Granuloma; Humans; Male; Middle Aged; Mycobacterium tuberculosis; Pleura; Pleurisy; Tuberculosis
PubMed: 33398944
DOI: 10.3346/jkms.2021.36.e10 -
Internal Medicine (Tokyo, Japan) Aug 2021
Topics: COVID-19; Humans; Lung; Pleura; SARS-CoV-2
PubMed: 34092732
DOI: 10.2169/internalmedicine.7183-21