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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.
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.
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.
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.
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.
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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.
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.
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.
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.