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1.
Trials ; 25(1): 249, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38594766

ABSTRACT

BACKGROUND: Malignant pleural effusion (MPE) is a debilitating condition as it commonly causes disabling breathlessness and impairs quality of life (QoL). Indwelling pleural catheter (IPC) offers an effective alternative for the management of MPE. However, IPC-related infections remain a significant concern and there are currently no long-term strategies for their prevention. The Australasian Malignant PLeural Effusion (AMPLE)-4 trial is a multicentre randomised trial that evaluates the use of topical mupirocin prophylaxis (vs no mupirocin) to reduce catheter-related infections in patients with MPE treated with an IPC. METHODS: A pragmatic, multi-centre, open-labelled, randomised trial. Eligible patients with MPE and an IPC will be randomised 1:1 to either regular topical mupirocin prophylaxis or no mupirocin (standard care). For the interventional arm, topical mupirocin will be applied around the IPC exit-site after each drainage, at least twice weekly. Weekly follow-up via phone calls or in person will be conducted for up to 6 months. The primary outcome is the percentage of patients who develop an IPC-related (pleural, skin, or tract) infection between the time of catheter insertion and end of follow-up period. Secondary outcomes include analyses of infection (types and episodes), hospitalisation days, health economics, adverse events, and survival. Subject to interim analyses, the trial will recruit up to 418 participants. DISCUSSION: Results from this trial will determine the efficacy of mupirocin prophylaxis in patients who require IPC for MPE. It will provide data on infection rates, microbiology, and potentially infection pathways associated with IPC-related infections. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee has approved the study (RGS0000005920). Results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12623000253606. Registered on 9 March 2023.


Subject(s)
Catheter-Related Infections , Pleural Effusion, Malignant , Humans , Pleural Effusion, Malignant/diagnosis , Pleural Effusion, Malignant/complications , Quality of Life , Mupirocin/adverse effects , Pleurodesis/methods , Talc/therapeutic use , Catheters, Indwelling/adverse effects , Catheter-Related Infections/diagnosis , Catheter-Related Infections/prevention & control , Anti-Bacterial Agents/adverse effects , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
2.
J Bronchology Interv Pulmonol ; 31(2): 155-159, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37982602

ABSTRACT

BACKGROUND: Pleural infections related to indwelling pleural catheters (IPCs) are an uncommon clinical problem. However, management decisions can be complex for patients with active malignancies due to their comorbidities and limited life expectancies. There are limited studies on the management of IPC-related infections, including whether to remove the IPC or use intrapleural fibrinolytics. METHODS: We conducted a retrospective cohort study of patients with active malignancies and IPC-related empyemas at our institution between January 1, 2005 and May 31, 2021. The primary outcome was to evaluate clinical outcomes in patients with malignant pleural effusions and IPC-related empyemas treated with intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) compared with those treated with tPA alone or no intrapleural fibrinolytic therapy. The secondary outcome evaluated was the incidence of bleeding complications. RESULTS: We identified 69 patients with a malignant pleural effusion and an IPC-related empyema. Twenty patients received tPA/DNase, 9 received tPA alone, and 40 were managed without fibrinolytics. Those treated with fibrinolytics were more likely to have their IPCs removed as part of the initial management strategy ( P =0.004). The rate of surgical intervention and mortality attributable to the empyema were not significantly different between treatment groups. There were no bleeding events in any group. CONCLUSION: In patients with IPC-related empyemas, we did not find significant differences in the rates of surgical intervention, empyema-related mortality, or bleeding complications in those treated with intrapleural tPA/DNase, tPA alone, or no fibrinolytics. More patients who received intrapleural fibrinolytics had their IPCs removed, which may have been due to selection bias.


Subject(s)
Empyema, Pleural , Pleural Effusion, Malignant , Pleural Effusion , Humans , Tissue Plasminogen Activator/therapeutic use , Fibrinolytic Agents/therapeutic use , Empyema, Pleural/drug therapy , Retrospective Studies , Pleural Effusion, Malignant/drug therapy , Pleural Effusion, Malignant/complications , Catheters, Indwelling/adverse effects , Deoxyribonucleases , Pleural Effusion/therapy
3.
JAAPA ; 36(12): 1-4, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37989195

ABSTRACT

ABSTRACT: Angiosarcoma is a rare and aggressive vascular malignancy that typically originates in the skin or soft tissue of the body. It is known to have a propensity for metastasis to the lung parenchyma in the form of pulmonary nodules and cavitary lesions; however, a less commonly described entity is in the form of a malignant pleural effusion. Management of a malignant pleural effusion due to angiosarcoma presents a unique challenge. This article describes the challenges faced during one patient's diagnostic and treatment course, and the anticipated future complications of his aggressive disease.


Subject(s)
Hemangiosarcoma , Lung Neoplasms , Pleural Effusion, Malignant , Pleural Effusion , Humans , Pleural Effusion, Malignant/therapy , Pleural Effusion, Malignant/complications , Hemangiosarcoma/diagnosis , Hemangiosarcoma/secondary , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Lung/pathology
4.
J Nippon Med Sch ; 89(6): 616-622, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-34840219

ABSTRACT

INTRODUCTION: Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma-type mesothelioma, comprising approximately 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, it may not be useful for DMPM because of the presence of desmoplasia and bland cellular atypia. We report a case, and previously undescribed cytological features, of DMPM that was diagnosed during autopsy. CASE PRESENTATION: A man in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. A chest CT scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. During autopsy, scrape-imprint smears were prepared and cytology of pleural effusions was performed. The scrape-imprint smear samples showed spindle cells with mild nuclear atypia and grooves with fibrous stroma. Pleural effusion cytology revealed spindle cells with mild nuclear atypia, as well as grooves with loose epithelial connections. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in the cytological samples, thus indicating a diagnosis of DMPM, which was confirmed by fluorescence in situ hybridization. CONCLUSION: Cytological procedures such as pleural effusion cytology and scrape-imprinting cytology may help in diagnosing rare tumors such as DMPM.


Subject(s)
Mesothelioma, Malignant , Mesothelioma , Pleural Effusion, Malignant , Pleural Effusion , Pleural Neoplasms , Humans , Male , Autopsy , In Situ Hybridization, Fluorescence , Mesothelioma/diagnosis , Mesothelioma, Malignant/complications , Pleural Effusion/complications , Pleural Effusion/pathology , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/pathology , Pleural Neoplasms/diagnosis , Middle Aged
5.
J Bronchology Interv Pulmonol ; 30(3): 238-243, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-35698287

ABSTRACT

BACKGROUND: Indwelling pleural catheters (IPCs) are frequently used for the management of malignant pleural effusions (MPEs), but drainage can be impaired by pleural loculations. We aimed to evaluate the safety and effectiveness of intrapleural tissue plasminogen activator (tPA) versus combination tPA-deoxyribonuclease (DNase) in the treatment of loculated MPE. METHODS: We performed a retrospective review of patients with confirmed or presumed MPEs requiring IPC insertion. We compared the efficacy of intrapleural tPA, tPA-DNase, and procedural intervention on pleural fluid drainage. Secondary endpoints included the need for future pleural procedures (eg, thoracentesis, IPC reinsertion, chest tube insertion, or surgical intervention), IPC removal due to spontaneous pleurodesis, and IPC-related complications. RESULTS: Among 437 patients with MPEs, loculations developed in 81 (19%) patients. Twenty-four (30%) received intrapleural tPA, 46 (57%) received intrapleural tPA-DNase, 4 (5%) underwent a procedural intervention, and 7 (9%) received ongoing medical management. tPA improved pleural drainage in 83% of patients, and tPA-DNase improved pleural drainage in 80% of patients. tPA alone may be associated with increased rates of spontaneous pleurodesis compared with tPA-DNase. There was no difference in complications when comparing tPA, combination tPA-DNase, procedural intervention, and no therapy. CONCLUSION: Both intrapleural tPA and combination tPA-DNase appear to be safe and effective in improving pleural fluid drainage in selected patients with loculated MPE, although further studies are needed.


Subject(s)
Pleural Effusion, Malignant , Pleural Effusion , Humans , Catheters, Indwelling , Deoxyribonucleases/therapeutic use , Drainage , Fibrinolytic Agents/therapeutic use , Pleural Effusion/etiology , Pleural Effusion, Malignant/drug therapy , Pleural Effusion, Malignant/complications , Retrospective Studies , Tissue Plasminogen Activator/therapeutic use
6.
Recenti Prog Med ; 114(1): 818-820, 2023 01.
Article in English | MEDLINE | ID: mdl-36573534

ABSTRACT

Diffuse large B-cell lymphoma is the most common histologic diagnosis among the aggressive lymphomas, accounting for 30% of all lymphomas. Human herpes virus 8-negative effusion-based lymphoma (HHV8-negative EBL) is a rare form of lymphoma, under recognized and still not well characterized in the literature. In contrast to primary effusion lymphoma (PEL), HHV8-negative EBL is characterized by malignant effusion in essentially serous body cavity with no detectable contiguous tumor masses and is no associated with human immunodeficiency virus and HHV8 infections. The presence of comorbid medical conditions can hide this type of lymphoma and made diagnosis more challenging. Here, we describe a rare case of an 82-year-old male suffering from peritoneal and pleural effusion and Hepatitis B virus related cirrhosis diagnosed with HHV8-negative EBL.


Subject(s)
Acquired Immunodeficiency Syndrome , Herpesviridae Infections , Herpesvirus 8, Human , Lymphoma , Pleural Effusion, Malignant , Male , Humans , Aged, 80 and over , Lymphoma/complications , Lymphoma/pathology , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/pathology , Herpesviridae Infections/complications
7.
Clin Transl Sci ; 16(1): 104-117, 2023 01.
Article in English | MEDLINE | ID: mdl-36253892

ABSTRACT

Indwelling pleural catheter (IPC) is widely used in patients with pleural effusion (PE). This meta-analysis aimed to comprehensively summarize the clinical complication from IPC. We searched four large electronic databases (PubMed, EMBASE, MEDLINE, and Cochrane Library) for potentially relevant studies and assessed the included studies' quality using the methodological index for nonrandomized studies' criteria. Extracted data were used to pool rates, and to conduct subgroup and meta-regression analyses. Forty-one studies involving a cumulative 4983 patients with 5650 IPCs were included in this meta-analysis. The overall incidence of IPC complications was 20.3% (95% confidence interval [CI]: 15.0-26.3). The top four complications were: overall infection incidence 5.7% (95% CI: 0.7-2.4); overall catheter abnormality incidence 4.4% (95% CI: 2.8-6.3); pain incidence 1.2% (95% CI: 0.4-2.4); and overall loculation incidence 0.9% (95% CI: 0.1-2.1). Subgroup and meta-regression analyses for overall complications and infections by country, PE site, and PE type demonstrated these factors did not contribute significantly to heterogeneity. Further subgroup analyses for infection of benign PE showed that the overall infection incidence (12.6% [95% CI: 8.1-17.8] vs 0.7% [95% CI: 0.0-4.5]) and empyema incidence (9.1% [95% CI: 5.3-13.8] vs 0.0% [95% CI: 0.0-2.3]) of patients with liver-related PE were significantly higher than that of patients with heart-related PE. Our meta-analysis showed reliable pooled incidences of IPC-related complications, with infection being the most common. These results serve to remind clinicians about the incidence of IPC-related complications and emphasize the importance of taking corresponding preventive and therapeutic steps.


Subject(s)
Pleural Effusion, Malignant , Pleural Effusion , Humans , Catheterization/adverse effects , Catheters, Indwelling/adverse effects , Incidence , Pleural Effusion/epidemiology , Pleural Effusion/etiology , Pleural Effusion/therapy , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/therapy
8.
Trials ; 23(1): 530, 2022 Jun 27.
Article in English | MEDLINE | ID: mdl-35761341

ABSTRACT

INTRODUCTION: Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. METHODS AND ANALYSIS: A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. ETHICS AND DISSEMINATION: Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. DISCUSSION: Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12618001013257 . Registered on 18 June 2018. PROTOCOL VERSION: Version 3.00/4.02.19.


Subject(s)
Pleural Effusion, Malignant , Catheters, Indwelling/adverse effects , Drainage/methods , Humans , Multicenter Studies as Topic , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/therapy , Pleurodesis/adverse effects , Pleurodesis/methods , Quality of Life , Randomized Controlled Trials as Topic , Talc , Thoracic Surgery, Video-Assisted/adverse effects
9.
Am J Ind Med ; 65(7): 620-623, 2022 07.
Article in English | MEDLINE | ID: mdl-35524457

ABSTRACT

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that originates from hyperplasia and metaplasia of the mesothelial cells that cover the pleural cavity. Previous exposure to asbestos is the main risk factor. Since MPM is often diagnosed at an advanced stage with rapid evolution and resistance to treatment, it is associated with an unfavorable outcome. Mesothelioma in situ (MIS) has been postulated as a preinvasive phase of MPM; however, its diagnostic criteria have been defined only recently. Diagnosis of MIS may represent an opportunity for early therapies with better results, but the optimal approach has not been defined thus far. Here, we report on a case of a 74-year-old man with right-sided pleural effusion and a previous history of occupational exposure to asbestos for 9 years who was diagnosed with MIS after a latency of 36 years. During follow-up, spontaneous disease regression was observed 5 months after the initial diagnosis; however, it recurred in the form of invasive epithelioid MPM. There is a paucity of literature on MIS and its evolution; however, our case provides relevant knowledge of this unusual behavior, which is important to define follow-up and therapeutic strategies for future cases.


Subject(s)
Asbestos , Mesothelioma, Malignant , Mesothelioma , Pleural Effusion, Malignant , Pleural Neoplasms , Aged , Asbestos/toxicity , Humans , Male , Mesothelioma/etiology , Pleural Effusion, Malignant/complications , Pleural Neoplasms/etiology
10.
Medicine (Baltimore) ; 101(52): e32207, 2022 Dec 30.
Article in English | MEDLINE | ID: mdl-36595983

ABSTRACT

BACKGROUND: Although there are new treatments for non-small cell lung cancer with malignant pleural effusion, these therapies are prone to recurrent pleural effusion and poor in efficacy. And recombinant human endostatin is a new type of anti-tumor angiogenesis drug independently developed in my country. It has the effect of inhibiting tumor angiogenesis, inhibiting tumor proliferation and differentiation, and effectively inhibiting the formation and recurrence of malignant pleural effusion. Therefore, this study is aim to systematically review the efficacy and safety of intrapleural injection of endostar combined with cisplatin in the treatment of non-small cell lung cancer (NSCLC) with malignant pleural effusion. METHODS: Databases including Cochrane Library, PubMed, CBM, Embase, CNKI, and WanFang Data were searched to collect randomized controlled trials about endostar combined with cisplatin for NSCLC with malignant pleural effusion from inception to April 2022. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in included studies. Finally, the meta-analysis was made by using RevMan 5.4.1 software. RESULTS: A total of 11 randomized controlled trials involving 814 patients were finally included. The results of the meta-analysis showed that: The overall response rate and the improvement rate of quality of life in the endostar combined with cisplatin group were higher than that of the cisplatin alone group (relative risk = 1.58, 95% confidence interval = 1.42-1.76, P < .00001; relative risk = 1.63, 95% confidence interval = 1.38-1.93, P < .00001, respectively). Meanwhile, there were no significant differences between the 2 groups in the incidence of gastrointestinal reaction, the incidence of leucopenia, the incidence of thrombocytopenia, and the incidence of hypodynamia (all P values > .05). CONCLUSION: Compared with cisplatin, intrapleural injection of endostar combined with cisplatin could improve the overall response rate and the quality of life of NSCLC patients with malignant pleural effusion. Due to the limited quality and quantity of included studies, more high-quality studies are needed to verify the above conclusion.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Pleural Effusion, Malignant , Humans , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/therapeutic use , Endostatins/therapeutic use , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/drug therapy , Quality of Life , Randomized Controlled Trials as Topic , Thrombocytopenia/epidemiology
11.
Nat Commun ; 12(1): 6690, 2021 11 18.
Article in English | MEDLINE | ID: mdl-34795282

ABSTRACT

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer.


Subject(s)
Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic/immunology , Immunophenotyping/methods , Pleural Effusion, Malignant/immunology , RNA-Seq/methods , Single-Cell Analysis/methods , Aged , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/immunology , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/complications , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Macrophages/classification , Macrophages/immunology , Macrophages/metabolism , Male , Middle Aged , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/genetics , T-Lymphocytes/classification , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology
13.
Cancer Sci ; 111(10): 3747-3758, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32706142

ABSTRACT

Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant-associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet-like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p-STAT3, HIF-1α and Nf-kB. VEGF/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.


Subject(s)
Lung Neoplasms/genetics , Pleural Effusion, Malignant/genetics , STAT3 Transcription Factor/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor Receptor-2/genetics , Aged , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cell Survival/genetics , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Female , Human Umbilical Vein Endothelial Cells , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Lung Neoplasms/complications , Lung Neoplasms/pathology , Male , NF-kappa B/genetics , Neovascularization, Pathologic/complications , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/pathology , Pleural Effusion/genetics , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/pathology
14.
BMJ Open Respir Res ; 7(1)2020 06.
Article in English | MEDLINE | ID: mdl-32527872

ABSTRACT

Background Despite improved screening techniques, diagnosis of lung cancer is often late and its prognosis is poor. In the present study, in vitro chemosensitivity of solid tumours and pleural effusions of lung adenocarcinomas were analysed and compared with clinical drug response.Methods Tumour cells were isolated from resected solid tumours or pleural effusions, and cryopreserved. Three-dimensional (3D) tissue aggregate cultures were set up when the oncoteam reached therapy decision for individual patients. The aggregates were then treated with the selected drug or drug combination and in vitro chemosensitivity was tested individually measuring ATP levels. The clinical response to therapy was assessed by standard clinical evaluation over an 18 months period.Results Based on the data, the in vitro chemosensitivity test results correlate well with clinical treatment response.Conclusions Such tests if implemented into the clinical decision making process might allow the selection of an even more individualised chemotherapy protocol which could lead to better therapy response.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/therapeutic use , Drug Screening Assays, Antitumor/methods , Lung Neoplasms/drug therapy , Pleural Effusion, Malignant/drug therapy , Adenocarcinoma/complications , Adenocarcinoma/pathology , Antineoplastic Agents/pharmacology , Feasibility Studies , Humans , Lung Neoplasms/complications , Lung Neoplasms/pathology , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/pathology , Prognosis , Tumor Cells, Cultured
15.
Thorac Cancer ; 11(7): 1876-1884, 2020 07.
Article in English | MEDLINE | ID: mdl-32421226

ABSTRACT

BACKGROUND: Pleurodesis is the standard of care for non-small cell lung cancer (NSCLC) patients with symptomatic malignant pleural effusion (MPE). However, there is no standard management for MPE uncontrolled by pleurodesis. Most patients with unsuccessful MPE control are unable to receive effective chemotherapy. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of MPE. This multicenter, phase II study investigated the effects of bevacizumab plus chemotherapy in nonsquamous NSCLC patients with unsuccessful management of MPE. METHODS: Nonsquamous NSCLC patients with MPE following unsuccessful tube drainage or pleurodesis received bevacizumab (15 mg/kg) plus chemotherapy every three weeks. The primary endpoint was pleural effusion control rate (PECR), defined as the percentage of patients without reaccumulation of MPE at eight weeks. Secondary endpoints included pleural progression-free survival (PPFS), safety, and quality of life (QoL). RESULTS: A total of 20 patients (median age: 69 years; 14 males; 20 adenocarcinomas; six epidermal growth factor receptor mutations) were enrolled in nine centers. The PECR was 80% and the primary end point was met. The PPFS and the overall survival (OS) were 16.6 months and 19.6 months, respectively. Patients with high levels of VEGF in the MPE had shorter PPFS (P = 0.010) and OS (P = 0.002). Toxicities of grade ≥ 3 included neutropenia (50%), thrombocytopenia (10%), proteinuria (10%), and hypertension (2%). The cognitive QoL score improved after treatment. CONCLUSIONS: Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE, and should be considered as a standard therapy in this setting. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Bevacizumab plus chemotherapy is highly effective with acceptable toxicities in nonsquamous NSCLC patients with uncontrolled MPE. WHAT THIS STUDY ADDS: Bevacizumab plus chemotherapy should be considered as a standard treatment option for patients with uncontrolled MPE. CLINICAL TRIAL REGISTRATION: UMIN000006868 was a phase II study of efficacy of bevacizumab plus chemotherapy for the management of malignant pleural effusion (MPE) in nonsquamous non-small cell lung cancer patients with MPE unsuccessfully controlled by tube drainage or pleurodesis (North East Japan Study Group Trial NEJ-013B) (http://umin.sc.jp/ctr/).


Subject(s)
Adenocarcinoma of Lung/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Pleural Effusion, Malignant/drug therapy , Pleurodesis/adverse effects , Adenocarcinoma of Lung/etiology , Adenocarcinoma of Lung/pathology , Aged , Bevacizumab/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/etiology , Carcinoma, Non-Small-Cell Lung/pathology , Docetaxel/administration & dosage , Erlotinib Hydrochloride/administration & dosage , Female , Follow-Up Studies , Humans , Lung Neoplasms/etiology , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/pathology , Pemetrexed/administration & dosage , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/pathology , Prognosis , Survival Rate
16.
Indian J Tuberc ; 67(1): 98-104, 2020 Jan.
Article in English | MEDLINE | ID: mdl-32192626

ABSTRACT

BACKGROUND: Tuberculous pleural effusion is the manifestation of Mycobacterium tuberculosis infection in pleura. With existing means, it is difficult to establish the diagnosis of tuberculosis (TB) and non-TB pleural effusions; thus, establishing the diagnosis of TB pleural effusion and non-TB pleural effusion is still a clinical problem. Tumour necrosis factor alpha (TNFα) is a potent inflammatory cytokine that plays an important role in immunity to Mycobacterium tuberculosis infections, this level of cytokine increases in pleural effusion due to tuberculosis. OBJECTIVE: To compare the TNF-α level of pleural fluid in TB and non-TB pleural effusion. METHODS: The samples in this study that fulfilled the inclusion criteria were patients with non-TB pleural tuberculosis effusion in the inpatient ward in Pulmonology Unit Dr. Soetomo General Hospital Surabaya, male and female, aged between 15 and 60 years. The data is divided into two: primary data and secondary data of patients who fulfilled inclusion and exclusion criteria. The data with normal distribution was analyzed using independent t2 test and if the data distribution is abnormal, it was analyzed using Fisher's exact test. RESULTS: There were 22 subjects divided into 2 groups that were 11 patients with TB pleural effusion and 11 patients with non-TB pleural effusion. The TNF-α level of pleural fluid in TB pleural effusion was 25.43±13.55pg/mL. The TNF-α level of pleural fluid in non-TB was 5.98±1.89pg/mL. The serum TNF-α level in TB pleural effusion was 83.22±88.15pg/mL. The serum TNF-α level in non-TB was 68.54±57.88pg/mL. There was higher level of TNF-α pleural fluid in TB pleural effusion than in non-TB pleural effusion (25.43±13.55pg/mL vs 5.98±1.89pg/mL, p value <0.05). The serum TNF-α level in patients with TB pleural effusion was higher than TNF-α serum level of non-TB pleural effusion. There was no significant difference between TNF-α level of pleural fluid and serum TNF-α levels in the TB pleural effusion group (p value >0.05). CONCLUSION: The TNF-α level of pleural fluid in TB pleural effusion was higher than non-TB pleural effusions and there was no significant difference between serum TNF-α levels in the TB pleural effusion group and in the non-TB pleural effusion group.


Subject(s)
Exudates and Transudates/metabolism , Pleural Effusion/metabolism , Tuberculosis, Pleural/metabolism , Tumor Necrosis Factor-alpha/metabolism , Adolescent , Adult , Aged , Case-Control Studies , Exudates and Transudates/chemistry , Female , Humans , Male , Middle Aged , Pleural Effusion/etiology , Pleural Effusion, Malignant/complications , Pleural Effusion, Malignant/metabolism , Pneumonia/complications , Pneumonia/metabolism , Tuberculosis, Pleural/blood , Tuberculosis, Pleural/complications , Tumor Necrosis Factor-alpha/blood , Young Adult
17.
Thorax ; 75(5): 432-434, 2020 05.
Article in English | MEDLINE | ID: mdl-32165417

ABSTRACT

Malignant pleural effusion is common and causes disabling symptoms such as breathlessness. Treatments are palliative and centred around improving symptoms and quality of life but an optimal management strategy is yet to be universally agreed. A novel pump system, allowing fluid to be moved from the pleural space to the urinary bladder, may have a role for the management of recurrent malignant pleural effusion. We hereby describe the first animal study using this device and the results of the first application in patients.


Subject(s)
Catheters, Indwelling , Implants, Experimental , Pleural Effusion, Malignant/therapy , Urinary Bladder , Animals , Disease Models, Animal , Dyspnea/etiology , Female , Humans , Middle Aged , Pleural Effusion, Malignant/complications , Prosthesis Failure , Prosthesis Implantation/methods , Recurrence , Swine
18.
Expert Opin Biol Ther ; 20(3): 319-326, 2020 03.
Article in English | MEDLINE | ID: mdl-32011207

ABSTRACT

Background: Immune-checkpoint inhibitors have radically changed the treatment landscape of Non-Small-Cell Lung Cancer (NSCLC). It is still unclear whether specific clinical characteristics might identify those patients benefiting from immunotherapy more than others. The aim of this study was to identify clinical characteristics associated with disease-specific survival (DSS), time-to-treatment failure (TTF), objective responses (OR) and progressive disease (PD) in NSCLC patients treated with Nivolumab.Methods: This was a multicenter retrospective study conducted on 294 patients treated with Nivolumab for advanced NSCLC.Results: Of the more than 50 variables analyzed, five showed a significant correlation with DSS: ECOG PS, size of the biggest brain metastasis, number of metastatic sites, toxicity, and malignant pleural effusion. Three variables significantly correlated with TTF: malignant pleural effusion, number of metastatic sites, number of liver metastases. Malignant pleural effusion was the only variable showing a significant correlation with OR, as well as the only one correlating with all the endpoints of the study.Conclusions: This study identified clinical characteristics associated with survival and response during treatment with Nivolumab in NSCLC patients. The unfavorable association between malignant pleural effusion and objective response is a novel finding with important translational implications.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Nivolumab/therapeutic use , Adult , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Pleural Effusion, Malignant/complications , Prognosis , Retrospective Studies , Treatment Outcome
19.
Arch Bronconeumol (Engl Ed) ; 56(3): 143-148, 2020 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-31253375

ABSTRACT

INTRODUCTION: Pleural disease involves a large number of admissions and long hospital stays. In order to improve this situation, a Pleural Unit (PU) was created in our hospital. Our aim was to analyze the clinical impact of this unit. MATERIAL AND METHODS: In this prospective study, we included patients admitted to the PU of the Hospital Universitario Central de Asturias for primary spontaneous pneumothorax (PSP), secondary spontaneous pneumothorax (SSP), complicated parapneumonic pleural effusion (CPPE), and malignant pleural effusion (MPE) between January 2015 and December 2018. We analyzed descriptive parameters, mean length of stay, readmissions at 1 month, need for surgery, and in the CPPE group, in-hospital mortality. The data were compared with those of patients admitted to the respiratory medicine department for the same diseases during the previous two years (2013-2014). We also describe all procedures performed in the PU, in both inpatients and outpatients. RESULTS: A total of 741 patients were included, We observed a progressive decrease in total admissions for pleural diseases and mean length of stay (days) (with the exception of MPE), as follows: PSP: from 6.2 to 4.2 (P=.004); SSP: 13.2 to 8.6 (P=.005), MPE: 10.3 to 12.3 (P=.05); and CPPE: 18.3 to 11.3 (P=.001) There was a reduction in hospital readmissions at 1 month and in in-hospital mortality due to CPPE in the PU period (14.9% to 5.5%) (P=.021). CONCLUSIONS: The creation of a PU could decrease the number of unnecessary admissions, and reduce mean lengths of stay and, in the case of CPPE, in-hospital mortality.


Subject(s)
Empyema, Pleural , Hospitalization , Pleural Effusion , Adult , Diagnosis, Differential , Empyema, Pleural/complications , Female , Hospital Mortality , Hospitals , Humans , Male , Middle Aged , Pleura/pathology , Pleural Effusion/complications , Pleural Effusion, Malignant/complications , Pneumothorax/complications , Prospective Studies
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