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Discerning the Primary Carcinoma in Malignant Peritoneal and Pleural Effusions Using Imaging Mass Spectrometry-A Feasibility Study.
Schwamborn K, Weirich G, Steiger K, Zimmermann G, Schmidmayr M, Weichert W, Caprioli RM
(2019) Proteomics Clin Appl 13: e1800064
MeSH Terms: Diagnosis, Differential, Feasibility Studies, Humans, Mass Spectrometry, Molecular Imaging, Peritoneal Neoplasms, Pleural Effusion, Malignant, Tissue Array Analysis
Show Abstract · Added March 3, 2020
PURPOSE - Malignant effusions challenge diagnostic accuracy due to cytomorphologic overlaps between various malignant primaries. Workup of this material to establish a correct diagnosis is time consuming and limited by the sparsity of material. In order to circumvent these drawbacks, the use of MALDI imaging MS (IMS) as a diagnostic platform has been explored.
EXPERIMENTAL DESIGN - Cytology cell blocks from malignant effusions (serous ovarian carcinoma and several non-ovarian carcinomas including gastric adenocarcinoma) containing at least 30% neoplastic cells are selected for generation of cytology microarrays (CMA). CMA sections are transferred to conductive glass slides, subjected to on-tissue tryptic digestion, and matrix application for MALDI-IMS analysis.
RESULTS - Supervised classification analysis identifies serous ovarian carcinomas as the source of malignant effusions with a sensitivity of 85.7% when compared to samples from all other included primary sites. When compared to gastric adenocarcinoma, serous ovarian carcinoma samples can be delineated with a sensitivity of 97.3%.
CONCLUSION AND CLINICAL RELEVANCE - These preliminary results highlight that MALDI-IMS allows subtyping of malignant effusions to identify the precise origin of neoplastic cells. While achieving similar results compared to classical approaches such as immunocytology, more material is conserved that will be available for further tests.
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Myeloid-derived interleukin-1β drives oncogenic KRAS-NF-κΒ addiction in malignant pleural effusion.
Marazioti A, Lilis I, Vreka M, Apostolopoulou H, Kalogeropoulou A, Giopanou I, Giotopoulou GA, Krontira AC, Iliopoulou M, Kanellakis NI, Agalioti T, Giannou AD, Jones-Paris C, Iwakura Y, Kardamakis D, Blackwell TS, Taraviras S, Spella M, Stathopoulos GT
(2018) Nat Commun 9: 672
MeSH Terms: Animals, Cell Line, Tumor, Chemokine CXCL1, Female, Genes, ras, Humans, I-kappa B Kinase, Interleukin-1beta, Male, Mice, Mice, Inbred C57BL, Mutation, Myeloid Cells, NF-kappa B, Pleural Effusion, Malignant, Receptors, Interleukin-1
Show Abstract · Added March 21, 2018
Malignant pleural effusion (MPE) is a frequent metastatic manifestation of human cancers. While we previously identified KRAS mutations as molecular culprits of MPE formation, the underlying mechanism remained unknown. Here, we determine that non-canonical IKKα-RelB pathway activation of KRAS-mutant tumor cells mediates MPE development and this is fueled by host-provided interleukin IL-1β. Indeed, IKKα is required for the MPE-competence of KRAS-mutant tumor cells by activating non-canonical NF-κB signaling. IL-1β fuels addiction of mutant KRAS to IKKα resulting in increased CXCL1 secretion that fosters MPE-associated inflammation. Importantly, IL-1β-mediated NF-κB induction in KRAS-mutant tumor cells, as well as their resulting MPE-competence, can only be blocked by co-inhibition of both KRAS and IKKα, a strategy that overcomes drug resistance to individual treatments. Hence we show that mutant KRAS facilitates IKKα-mediated responsiveness of tumor cells to host IL-1β, thereby establishing a host-to-tumor signaling circuit that culminates in inflammatory MPE development and drug resistance.
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16 MeSH Terms
The diagnosis of pleural effusions.
Porcel JM, Azzopardi M, Koegelenberg CF, Maldonado F, Rahman NM, Lee YC
(2015) Expert Rev Respir Med 9: 801-15
MeSH Terms: Humans, Pleural Effusion
Show Abstract · Added February 1, 2016
Pleural effusions arise from a variety of systemic, inflammatory, infectious and malignant conditions. Their precise etiological diagnosis depends on a combination of medical history, physical examination, imaging tests and pertinent pleural fluid analyses; including specific biomarkers (e.g., natriuretic peptides for heart failure, adenosine deaminase for tuberculosis, or mesothelin for mesothelioma). Invasive procedures, such as pleuroscopic biopsies, may be required for persistently symptomatic effusions which remain undiagnosed after the analysis of one or more pleural fluid samples. However, whenever parietal pleural nodularity or thickening exist, image-guided biopsies should first be attempted. This review addresses the current diagnostic approach to pleural effusions secondary to heart failure, pneumonia, cancer, tuberculosis and other less frequent conditions.
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The Use of Indwelling Tunneled Pleural Catheters for Recurrent Pleural Effusions in Patients With Hematologic Malignancies: A Multicenter Study.
Gilbert CR, Lee HJ, Skalski JH, Maldonado F, Wahidi M, Choi PJ, Bessich J, Sterman D, Argento AC, Shojaee S, Gorden JA, Wilshire CL, Feller-Kopman D, Ortiz R, Nonyane BAS, Yarmus L
(2015) Chest 148: 752-758
MeSH Terms: Adult, Aged, Aged, 80 and over, Catheters, Indwelling, Drainage, Female, Hematologic Neoplasms, Humans, Male, Middle Aged, Palliative Care, Pleural Effusion, Malignant, Retrospective Studies, Treatment Outcome
Show Abstract · Added July 28, 2015
BACKGROUND - Malignant pleural effusion is a common complication of advanced malignancies. Indwelling tunneled pleural catheter (IPC) placement provides effective palliation but can be associated with complications, including infection. In particular, hematologic malignancy and the associated immunosuppressive treatment regimens may increase infectious complications. This study aimed to review outcomes in patients with hematologic malignancy undergoing IPC placement.
METHODS - A retrospective multicenter study of IPCs placed in patients with hematologic malignancy from January 2009 to December 2013 was performed. Inclusion criteria were recurrent, symptomatic pleural effusion and an underlying diagnosis of hematologic malignancy. Records were reviewed for patient demographics, operative reports, and pathology, cytology, and microbiology reports.
RESULTS - Ninety-one patients (mean ± SD age, 65.4 ± 15.4 years) were identified from eight institutions. The mean × SD in situ dwell time of all catheters was 89.9 ± 127.1 days (total, 8,160 catheter-days). Seven infectious complications were identified, all of the pleural space. All patients were admitted to the hospital for treatment, with four requiring additional pleural procedures. Two patients died of septic shock related to pleural infection.
CONCLUSIONS - We present, to our knowledge, the largest study examining clinical outcomes related to IPC placement in patients with hematologic malignancy. An overall 7.7% infection risk and 2.2% mortality were identified, similar to previously reported studies, despite the significant immunosuppression and pancytopenia often present in this population. IPC placement appears to remain a reasonable clinical option for patients with recurrent pleural effusions related to hematologic malignancy.
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14 MeSH Terms
Medical thoracoscopy.
Skalski JH, Astoul PJ, Maldonado F
(2014) Semin Respir Crit Care Med 35: 732-43
MeSH Terms: Biopsy, Diagnosis, Differential, Humans, Pleural Diseases, Pleural Effusion, Malignant, Thoracic Surgery, Video-Assisted, Thoracoscopy
Show Abstract · Added July 28, 2015
The burden of pleural diseases continues to rise and affects an increasingly complex and aging patient population. As such, thoracentesis is one of the most common procedures performed by respiratory physicians, as pleural fluid analysis can establish the diagnosis of pleural effusions in approximately 75% of the cases. When a diagnosis is not reached, options include image-guided biopsies, only possible when focal pleural lesions can be identified by computed tomography or ultrasound; closed pleural biopsies, associated with a relatively low diagnostic yield; and surgical pleural biopsies, which typically require general anesthesia and a hospital stay. Medical thoracoscopy addresses some of the limitations of these techniques, allows a comprehensive pleural examination and targeted pleural biopsies, and offers the possibility of treatment of recurrence in the same setting. As such, medical thoracoscopy is ideally positioned as a valuable tool in the diagnosis of unexplained exudative pleural effusions.
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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7 MeSH Terms
Impact of pleural manometry on the development of chest discomfort during thoracentesis: a symptom-based study.
Pannu J, DePew ZS, Mullon JJ, Daniels CE, Hagen CE, Maldonado F
(2014) J Bronchology Interv Pulmonol 21: 306-13
MeSH Terms: Aged, Aged, 80 and over, Chest Pain, Cohort Studies, Drainage, Dyspnea, Female, Humans, Linear Models, Male, Manometry, Middle Aged, Paracentesis, Pleural Effusion, Pneumothorax, Pressure, Pulmonary Edema, Retrospective Studies, Thoracic Surgical Procedures, Ultrasonography
Show Abstract · Added July 28, 2015
BACKGROUND - Routine manometry is recommended to prevent complications during therapeutic thoracentesis, but has not definitively been shown to prevent pneumothorax or reexpansion pulmonary edema. As chest discomfort correlates with negative pleural pressures, we aimed to determine whether the use of manometry could anticipate the development of chest discomfort during therapeutic thoracentesis.
METHODS - A retrospective chart review of 214 consecutive adults who underwent outpatient therapeutic thoracentesis at our institution between January 1, 2011 and June 30, 2013 was performed. We compared preprocedural to postprocedural discomfort (using a linear analog scale from 0 to 10) in patients undergoing thoracentesis with or without manometry. We used a multivariate model to adjust for possible confounders. Changes of dyspnea scores were also analyzed.
RESULTS - Manometry was performed in 82/214 patients (38%). On univariate and multivariate analyses, neither the change in chest discomfort nor dyspnea scores was significantly different in the manometry versus the control group (P=0.12 and 0.24, respectively). Similar results were also found in the subgroup of large-volume thoracentesis (P=0.32 for discomfort, P=1.0 for dyspnea).
CONCLUSIONS - In our retrospective study, the use of manometry did not appear to anticipate the development of chest discomfort during therapeutic thoracentesis. Prospective studies are needed to confirm these findings.
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20 MeSH Terms
Pleural effusion following blunt splenic injury in the pediatric trauma population.
Kulaylat AN, Engbrecht BW, Pinzon-Guzman C, Albaugh VL, Rzucidlo SE, Schubart JR, Cilley RE
(2014) J Pediatr Surg 49: 1378-81
MeSH Terms: Adolescent, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Length of Stay, Male, Multiple Trauma, Pleural Effusion, Retrospective Studies, Spleen, Thoracoscopy, Wounds, Nonpenetrating
Show Abstract · Added August 26, 2015
BACKGROUND - Pleural effusion is a potential complication following blunt splenic injury. The incidence, risk factors, and clinical management are not well described in children.
METHODS - Ten-year retrospective review (January 2000-December 2010) of an institutional pediatric trauma registry identified 318 children with blunt splenic injury.
RESULTS - Of 274 evaluable nonoperatively managed pediatric blunt splenic injures, 12 patients (4.4%) developed left-sided pleural effusions. Seven (58%) of 12 patients required left-sided tube thoracostomy for worsening pleural effusion and respiratory insufficiency. Median time from injury to diagnosis of pleural effusion was 1.5days. Median time from diagnosis to tube thoracostomy was 2days. Median length of stay was 4days for those without and 7.5days for those with pleural effusions (p<0.001) and 6 and 8days for those pleural effusions managed medically or with tube thoracostomy (p=0.006), respectively. In multivariate analysis, high-grade splenic injury (IV-V) (OR 16.5, p=0.001) was associated with higher odds of developing a pleural effusion compared to low-grade splenic injury (I-III).
CONCLUSIONS - Pleural effusion following pediatric blunt splenic injury has an incidence of 4.4% and is associated with high-grade splenic injuries and longer lengths of stay. While some symptomatic patients may be successfully managed medically, many require tube thoracostomy for progressive respiratory symptoms.
Copyright © 2014 Elsevier Inc. All rights reserved.
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15 MeSH Terms
Symptom relief after large-volume thoracentesis in the absence of lung perfusion.
Klecka ME, Maldonado F
(2014) Chest 145: 1141-1143
MeSH Terms: Dyspnea, Humans, Male, Middle Aged, Pleural Effusion, Pulmonary Circulation, Recovery of Function, Recurrence, Respiratory Function Tests, Thoracostomy, Ventilation-Perfusion Ratio
Show Abstract · Added July 28, 2015
The physiologic basis for relief from dyspnea after therapeutic thoracentesis remains poorly understood. Here, we describe the case of a 46-year-old man with large recurrent pleural effusion with absent perfusion to the affected lung who experienced dramatic dyspnea relief after large-volume thoracentesis. This patient's improvement in breathlessness cannot be attributed to improved gas exchange and suggests the primary physiologic basis for the relief in dyspnea is a change in respiratory system mechanics or work of breathing.
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11 MeSH Terms
The lymphatic system in malignant pleural effusion. Drain or immune switch?
Marazioti A, Blackwell TS, Stathopoulos GT
(2014) Am J Respir Crit Care Med 189: 626-7
MeSH Terms: Animals, Pleural Effusion, Malignant, Th1 Cells, Th17 Cells
Added March 25, 2014
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4 MeSH Terms
Feasibility and safety of outpatient medical thoracoscopy at a large tertiary medical center: a collaborative medical-surgical initiative.
DePew ZS, Wigle D, Mullon JJ, Nichols FC, Deschamps C, Maldonado F
(2014) Chest 146: 398-405
MeSH Terms: Aged, Clinical Competence, Cooperative Behavior, Diagnosis, Differential, Feasibility Studies, Female, Follow-Up Studies, Humans, Male, Minnesota, Outpatients, Pleural Effusion, Reproducibility of Results, Retrospective Studies, Tertiary Care Centers, Thoracoscopy
Show Abstract · Added February 1, 2016
BACKGROUND - Medical thoracoscopy (MT) is performed by relatively few pulmonologists in the United States. Recognizing that an outpatient minimally invasive procedure such as MT could provide a suitable alternative to hospitalization and surgery in patients with undiagnosed exudative pleural effusions, we initiated the Mayo Clinic outpatient MT program and herein report preliminary data on safety, feasibility, and outcomes.
METHODS - All consecutive patients referred for outpatient MT from October 2011 to August 2013 were included in this study. Demographic, radiographic, procedural, and histologic data were recorded prospectively and subsequently analyzed.
RESULTS - Outpatient MT was performed on 51 patients, with the most common indication being an undiagnosed lymphocytic exudative effusion in 86.3% of the cohort. Endoscopic findings included diffuse parietal pleural inflammation in 26 patients (51%), parietal pleural studding in 19 patients (37.3%), a normal examination in three patients (5.9%), diffuse parietal pleural thickening in two patients (3.9%), and a diaphragmatic defect in one patient (2%). Pleural malignancy was the most common histologic diagnosis in 24 patients (47.1%) and composed predominantly of mesothelioma in 14 (27.5%). Nonspecific pleuritis was the second most frequent diagnosis in 23 patients (45.1%). There were very few complications, with no significant cases of hemodynamic or respiratory compromise and no deaths.
CONCLUSIONS - Outpatient MT can be integrated successfully into a busy tertiary referral medical center through the combined efforts of interventional pulmonologists and thoracic surgeons. Outpatient MT may provide patients with a more convenient alternative to an inpatient surgical approach in the diagnosis of undiagnosed exudative pleural effusions while maintaining a high diagnostic yield and excellent safety.
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16 MeSH Terms