The Frequency, Risk Factors, and Management of Complications From Pleural Procedures

Local anesthetic thoracoscopy (LAT) is important in the diagnosis of unilateral pleural effusions. Indwelling pleural catheters (IPC) can be inserted during LAT if a nonexpandable lung is suspected. Subcutaneous emphysema (SCE) is a known complication and is associated with increased morbidity and length of stay. It is unclear however if the incidence of SCE is affected if IPC is inserted through a separate incision to the LAT port. We aim to establish the incidence and grading of SCE when IPC is inserted during LAT and to determine if the site of IPC placement influences this. Retrospective analysis of LAT electronic records and radiology images over 8 years in a University Hospital. The incidence of SCE was assessed during admission and follow-up with the severity of SCE graded 0 to 4 (0 none; 1 at IPC site; 2 ipsilateral chest wall; 3 ipsilateral neck; 4 contralateral chest wall). 55 combined LAT and IPC procedures were performed. In 28 patients the IPC was inserted through the LAT port and in 27 the IPC was inserted in a separate intercostal space (ICS) to the LAT port. On day zero, the incidence of any SCE was lower if the IPC was inserted using a separate ICS to the LAT port compared with the same site as the LAT port( P =0.01). This was similarly reduced on discharge chest radiographs and subsequent follow-up. IPC insertion at LAT using a separate ICS to the LAT port is associated with a reduction in the incidence of SCE during admission and follow-up.

Introduction: Liver transplantation is the treatment of choice for decompensated liver disease, and by extension for hepatic hydrothorax. Persistent pleural effusions make it challenging for patients to maintain physiological fitness for transplantation. Indwelling pleural catheters (IPCs) provide controlled pleural fluid removal, including peri-operatively. The immune dysfunction of cirrhosis heightens susceptibility to bacterial infection and concerns exist regarding the sepsis potential from a tunnelled drain.Method: Six patients were identified who underwent IPC insertion for hepatic hydrothorax before successful liver transplantation, between November 2016 and November 2017.Results: All patients had recurrent transudative right sided pleural effusions. Mean age was 49 years (range 24–64) and mean United Kingdom Model for End-Stage Liver Disease score was 58. Four patients required correction of coagulopathy before insertion. There were no complications secondary to bleeding. Three patients were taught self-drainage at home of up to 1 litre (L) daily. A protocol was developed to ensure weekly review, pleural fluid culture and drainage of larger volumes in hospital. For every 2–3 L of pleural fluid drained, 100 mls of 20% Human Albumin Solution (HAS) was administered. On average an IPC was in situ for 58 days before surgery and drained 19 L of fluid in hospital. There was a small increase in average BMI (0.2) and serum albumin (2.1 g/L) at transplantation. There was one episode of stage one acute kidney injury secondary to high volume drainage. No further ascitic or pleural procedures were needed while an IPC was in situ. One thoracentesis was required after IPC removal. On average IPCs remained in situ for 7 days post transplantation and drained a further 2 L of fluid. Pleural fluid sampling was acquired on 92% of drainages in hospital. Of 44 fluid cultures, 2 cultured bacteria. Two patients had their IPCs and all other lines removed post transplantation due to suspected infection.Conclusion: Our case series describes a novel protocol and successful use of IPCs in the management of refractory hepatic hydrothorax as a bridge to liver transplantation. The protocol includes albumin replacement during pleural drainage, regular clinical review and culture of pleural fluid, with the option of self-drainage at home.

Pleural procedures are essential for the investigation and management of pleural disease and can be associated with significant morbidity and mortality. There is a lack of pleural procedure complication data in the Australian and New Zealand region. To review pleural procedure practices at Wollongong Hospital with an emphasis on the assessmentof complications, use of thoracic ultrasound (TUS), pathology results and comparison of findings with international data. Retrospective analysis of medical records was performed on pleural procedures identified through respiratory specialist trainee logbooks at Wollongong Hospital from January 2018 to December 2021. Comparison of complication rates was made to the British Thoracic Society 2011 a national pleural audit. One hundred and twenty-one pleural procedures were identified. There were 71 chest drains, 49 thoracocentesis and one indwelling pleural catheter (IPC) insertion. Ninety-seven per cent of procedures were performed for pleural effusions and 3% for pneumothorax. This audit demonstrated a complication rate (excluding pain) of 16.9% for chest drains and 4.1% for thoracocentesis. This gave an overall complication event rate of 10.8% (excluding pain) for pleural procedures. There was no major bleeding, organ puncture, pleural space infection or death. Bedside TUS was used in 99% of procedures. Complication rates for pleural procedures performed by respiratory specialist trainees at Wollongong Hospital are comparable with international outcomes. This audit provides data for comparison on pleural procedure complication rates in Australia. Future studies are required to determine complication rates with IPCs.

The Clinical and Economic Implications of Different Treatment Pathways for Patients With Rapidly Recurrent Malignant Pleural Effusion

Sir, Malignant pleural effusion heralds a poor prognosis with a median survival ranging from 3 to 12 months. These patients are mostly candidates for palliative therapy which includes alleviation of dyspnoea and facilitating the patient to spend the rest of their life at home with minimal hospitalisations. There are three main modalities of management in malignant pleural effusion, namely, repeated needle thoracentesis, intercostal tube drainage with chemical pleurodesis, and indwelling pleural catheter (IPC). Chemical pleurodesis has always been the first-line approach for malignant pleural effusions, but it requires apposition of pleural surfaces and a mean duration of hospital stay of 4 days.[1] An IPC is a multi-fenestrated silicone tube which is inserted aseptically, allowing long-term access to pleural space. The catheter is tunnelled through a short section of subcutaneous tissue and has a cuff that acts as a focal point for fibrous growth to allow the drain to remain in place. The catheter has a one-way access valve designed to be attached to a proprietary vacuum drainage bottle or a suction machine. The pre-vacuumed bottles provide the advantage of home drainage of the pleural fluid and are calibrated to drain only one litre of fluid, which prevents re-expansion pulmonary oedema during unsupervised drainage at home. Even though there is large international data on the use and advantage of IPC, there is paucity of Indian data regarding the same with only one case report published to the best of our knowledge.[2] This is why we would like to report our early experience on managing poor performance malignant pleural effusion using IPC in the Indian population. We inserted IPC in six patients with malignant pleural effusion who either had a moderate to high risk as per LENT score (LDH level in pleural fluid, ECOG performance scale, neutrophil lymphocyte ratio, tumour type) or had a trapped lung. IPCs were inserted aseptically on an out-patient basis, and patients were followed up for 3 months [Figure 1]. For the initial 1-week, daily drainage of the pleural fluid was carried out on an out-patient basis using a low-pressure suction pump, following which symptom-guided home drainage of the pleural fluid was performed using vacuum bottles. The daily visual analogue score (VAS) score (0–100) was recorded for the first 1 week, followed by 3, 6, 9, and 12 weeks. Patients were reviewed on an out-patient basis every third week, during which their dyspnoea was assessed using VAS and the catheter was inspected for any complications. During the 3 months follow-up or follow-up till death (whichever was earlier), the number and duration of hospital admissions for pleural effusion-related complaints and the number of auto-pleurodesis (defined as less than 50 ml drain for 3 consecutive days with radiological apposition of the pleural surface and no evidence of loculated collection or catheter blockage) were noted.Figure 1: Steps of IPC insertionOut of six patients who were managed with IPC, three were male and three were female. Metastatic lung carcinoma was the most common cause of pleural effusion in this group of patients (n = 3, 50%). Other causes of malignant pleural effusion were carcinoma breast, hepatocellular carcinoma, and angiosarcoma. The mean age of patients was 59 years (SD 19 years). All patients had symptomatic malignant pleural effusion with moderate to high LENT scores (mean 5, SD 1). One patient had a trapped lung. Five patients had unilateral pleural effusion, whereas one had bilateral effusion. During follow-up, two patients died, two patients had the IPC removed at the sixth and seventh weeks post insertion because of auto-pleurodesis, one patient had IPC removed at the sixth week because of pleural space infection, and one patient continued draining through IPC for 3 months. The median duration of catheter drainage was 60 days. Five out of six patients did not require any hospital admission for effusion-related complaints. One patient was admitted for 3 days in hospital, and IPC was removed and replaced with a large bore inter-coastal drainage tube because of pleural space infection. The mean breathlessness on presentation as per VAS was 80.83. Post IPC insertion and drainage, VAS dropped to a mean value of 45.83. This relief of breathlessness was maintained throughout the study period [Table 1]. Two out of the six patients had auto-pleurodesis. The patients who achieved auto-pleurodesis were an 88-year-old male and a 66-year-old female, both of whom had an adenocarcinoma lung with malignant pleural effusion. Auto-pleurodesis was achieved after a mean duration of 7 weeks of drainage.Table 1: Degree of dyspnoea as per visual analogue scale before and after insertion of IPCThe main advantage of IPC over chemical pleurodesis is the reduced number of days spent in hospital. Randomised control trial by Putnam et al.[3] showed the mean duration of hospital admission in chemical pleurodesis patients to be 7 days, whereas IPCs could be safely used as an out-patient procedure requiring no hospital admission. The second therapeutic intervention in malignant effusion trial (TIME 2 trial) and Australian malignant pleural effusion trial (AMPLE trial) also showed fewer effusion related hospital admissions post IPC insertion. In our experience, we were able to replicate these results with five out of our six patients requiring no hospital admissions. Patients were able to self-drain the effusion when symptomatic while at the comfort of their home. Even though a tunnelled tract of IPC, a cuff, and a one-way valve are designed to prevent ascending infection, catheter-associated pleural space infection can complicate IPC. A large multi-centre review of 1021 patients with IPC found an infection rate of 4.8%.[4] In our experience, one out of our six patients (with hepatocellular carcinoma as the cause of malignant pleural effusion) developed pleural space infection requiring hospital admission, replacement of IPC with a wide bore inter-coastal drainage tube, and antibiotics. TIME 2 trial was the first to examine whether using an IPC or the instillation of talc slurry via a chest tube was effective at relieving dyspnoea. Dyspnoea improved in both groups, with no significant difference in the mean VAS. In our experience, all our patients had statistically significant symptom relief with IPC drainage which was maintained throughout the study with initial aggressive pleural fluid drainage and later symptom-guided pleural fluid drainage. In this way, IPCs offer the advantage of dyspnoea relief with symptom-guided at-home self-drainage using vacuum bottles. One of the major limiting factors of IPC is cost. The catheter is much costlier than routine inter-coastal drainage, and there is recurring cost of single use pre-vacuumed bottles. Interestingly, a Dutch analysis of cost of IPC showed a mean cost of IPC comparable with that of chemical pleurodesis.[5] This is because of the cost of in-patient care which is reduced in IPC drainage. There are no studies regarding the same in the Indian population. In conclusion, IPCs are a novel method for management of malignant pleural effusion which offers good symptom relief with the added advantage of reduced hospital admissions, the option of which should be offered to all patients with malignant pleural effusion. Further studies in the Indian population are required to assess the improvement in quality of life and cost effectiveness as compared to conventional management. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

INDWELLING PLEURAL CATHETERS FOR TREATMENT OF RECURRENT PLEURAL EFFUSION DUE TO CONGESTIVE HEART FAILURE: A SINGLE CENTER EXPERIENCE

This section reviews papers published in Respirology in 2014 regarding prevention, novel diagnostic techniques, translational research and treatments for lung cancer. Other important developments in this field are also addressed. Cannabis is the most commonly used illicit substance worldwide.1 Although cannabis is known to contain harmful and carcinogenic substances, little is understood with regard to its effects on respiratory health, such as the potential for chronic obstructive pulmonary disease (COPD) and lung cancer. Gates et al.2 reported the results of an excellent review regarding cannabis smoking and respiratory health. Based on the previous literature, chronic cannabis use is associated with an increased prevalence of symptoms of chronic bronchitis.3 In contrast, the relationship between cannabis and lung cancer is contentious, although some papers have suggested a positive association. What about electronic cigarettes (e-cigarettes)? Are they safe or potentially harmful? E-cigarettes or electronic nicotine delivery system (ENDS) devices deliver a vaporized liquid to the lungs that usually contains nicotine and other chemicals. While some studies have shown that individuals who do not intend to quit smoking may reduce their intake of combustible cigarettes by smoking e-cigarettes, other studies have failed to show the superiority of this approach over the use of nicotine replacement medicine in individuals trying to quit smoking.4 Therefore, the potential benefits of ENDS are not well proven. In contrast, the inhalation of vapor from e-cigarette cartridges has been shown to enhance inflammatory changes in mouse airways, and the short-term use of e-cigarettes has been shown to adversely affect the lung function. Therefore, e-cigarettes are considered to be potentially harmful. Lam D et al.4 mentioned, in an editorial published in Respirology, that the Asian Pacific Society of Respirology (APSR) fully supports the joint statement by the Forum of International Respiratory Societies (FIRS) on the use of e-cigarettes, that electronic nicotine delivery devices should be restricted or banned until more information about their safety is available. The incidence of adenocarcinoma (Ad) has increased, while that of squamous cell carcinoma (Sq) and small cell lung carcinoma (SCLC) has decreased in Europe, North America and Japan.5 However, few studies have assessed the incidence and histological type of lung cancer in China. Kong et al.6 reported the findings of a population-based study of the incidence of lung cancer in Tianjin, the third largest city in China, during the period of 1981–2005. According to their report, the most common histological type is Sq in males and Ad in females. However, during the 25-year study period, the age-adjusted incidence of Sq declined sharply, while that of Ad continued to increase among younger groups. The authors concluded that tailored strategies for prevention and control should be developed to meet the needs of various populations. In Respirology, Alcada et al.7 evaluated the features of mediastinal lymphadenopathy on computed tomography (CT) and the clinical data of 217 human immunodeficiency virus (HIV) patients in the era of combination antiretroviral therapy. Among these patients, 52 were identified to have mediastinal lymphadenopathy, and 17 (33%) were diagnosed with pulmonary malignancy, including lung cancer. Larger lymph nodes were associated with increased odds of malignancy (OR 2.89; 95% confidence interval 1.24–6.1) according to a multivariate analysis. The reason for the high association between lung malignancy and HIV was discussed; however, the mechanisms remain unknown. The authors emphasized the need for a histological diagnosis in patients exhibiting swollen mediastinal lymph nodes. Although the National Lung Cancer Screening Trial (NLST) demonstrated that the application of low-dose computed tomography (LDCT) is useful for reducing lung cancer-related mortality,8 whether the detection of subcentimeter non-calcified nodules without changes in size over a 2-year follow-up period are indicative of malignancy or should be further followed up remains unknown. Shin et al.9 performed a retrospective study to answer this question. The authors investigated 635 subjects who received follow-up for LDCT for an initial 2-year screening period with three additional years thereafter in whom non-calcified subcentimeter nodules were evaluated. A total of 1107 subcentimeter nodules (1037 solid, 70 ground-glass opacity nodules) were detected. All solid subcentimeter nodules exhibiting stability for the initial 2-year period on screening LDCT were considered benign, as none of these lesions showed growth in the subsequent period. In contrast, subcentimeter GGNs have a greater potential for growth than solid nodules and require further follow-up with CT for more than 2 years, as some of them could be malignant. As a result of the increasing rate of detection of lung cancer nodules during lung cancer screening using CT, the development of a non-invasive diagnostic method for reducing the risks associated with biopsies is warranted. Confocal laser endoscopy (CLE) allows for real-time non-invasive histological imaging, and a probe-based CLE (pCLE) method has been developed in which the probe can be passed into the distal airway via the working channel of the bronchoscope, thus obtaining an optical biopsy sample. Meanwhile, Sorokina et al.10 performed an ex vivo study to evaluate the correlations between light microscopic findings and pCLE imaging findings of primary lung cancer. The authors examined 18 lobectomy samples from 18 different patients and found that pCLE can be used to identify lung carcinoma in ex vivo samples. Certain light microscopic features of lung carcinoma may be visualized on pCLE. These results suggest that pCLE is a non-invasive diagnostic method for making the histological diagnosis of nodules detected on CT scans. The volume doubling time (VDT) can be calculated using serial CT scans and may be applied to evaluate indeterminate pulmonary nodules detected at lung cancer screening. A retrospective study of VDT in surgically resected non-small cell lung cancer patients was recently reported by Mackintosh et al.11 The authors investigated 109 eligible scans in 46 patients with lung cancer (36 Ad, six Sq, two large cell and two carcinoids) and demonstrated that the non-small cell lung carcinoma (NSCLC) growth rate appears to be highly variable and related to both the histological subtype and smoking history, but not the presence of symptoms at diagnosis. Relatively slow-growing Ad lesions frequently metastasize. Araz et al.12 examined the correlations between the Ki-67, p53, transforming growth factor (TGF)-b and lysyl oxidase (LOX) values and the metastatic stage in various types of lung cancers. Consequently, high levels of cellular LOX and TGF-b were found to be related to an increased incidence of distant metastasis in Ad patients. LOX and TGF-b may therefore be useful markers of metastatic disease in patients with Ad. Furthermore, Ming et al.13 evaluated the diagnostic utility of the vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) and specificity protein-1 (SP-1) mRNA expression levels in cells obtained via bronchial brushing in 93 patients with lung cancer and 51 benign pulmonary lesions as a control. In the cancer group, the VEGF mRNA levels were significantly correlated with the SP-1 mRNA levels (P < 0.01) and showed the highest diagnostic rate, with a sensitivity of 89.2% and accuracy of 90.3%. These values were significantly better than those for cytology (P < 0.01). The authors concluded that the detection of VEGF mRNA and SP-1 mRNA in bronchial brushing cells may be useful for identifying early-stage lung cancer. Ost et al. and Yasufuku et al. both published excellent reviews with regard to multi-modality systematic approaches to mediastinal lymph node staging and the role of the bronchoscopist in identifying molecular profiles in cases of non-small cell lung cancer, respectively14, 15 Accurate and efficient lymph node staging is essential for selecting the treatment modality, and determining the molecular profile of the tumour is necessary for choosing appropriate molecular target drugs and prolonging the patient's survival. Qvale et al.16 showed that paraneoplastic Hu and collapsing response mediator protein 5 antibodies, which were originally thought to be specific markers for paraneoplastic syndrome, are found only in smokers without cancer or neurological disease using sera obtained from 552 smokers (379 smokers with and 173 without COPD) and 300 healthy controls. Preoperative physiological assessments are important for accurate patient selection and to provide appropriate treatment. Although the Eastern Cooperative Oncology Group (ECOG) performance status (PS) is usually used in clinical practice, its accuracy is not satisfactory. Therefore, Roman et al.17 compared the peak oxygen consumption (VO2 peak) with the ECOG PS in order to evaluate the clinical utility of the VO2 peak in operable patients with non-small cell lung cancer. The authors employed 392 NSCLC patients. PS scoring systems do not provide sensitive measurements of the functional status. Therefore, the authors concluded that the VO2 peak may be useful in the clinical management of oncology patients. Patients with advanced adenoid cystic carcinoma (ACC) of the central airway often develop fibrotic airway stenosis following radiotherapy. Eom et al.18 revealed the clinical utility of bronchoscopic intervention, including silicone airway stenting, in such patients. Forty-seven patients with ACC who received radiotherapy were analysed. Twenty-three per cent of the patients suffered from fibrotic airway stenosis after radiotherapy and underwent bronchoscopic intervention. The authors demonstrated this intervention to be safe and useful for treating airway stenosis after radiotherapy in patients with ACC. The intrapleural delivery of a commercially available compound made up of proteins produced by Staphylococcus aureus is used clinically to induce pleurodesis. Lansley et al.19 reported the findings of a proof-of-principle study showing the efficacy of inhibiting mesothelioma growth with a compound consisting of Staphylococcus aureus bioproducts. The authors demonstrated that in addition to its pleurodesing effect, this bacterial compound has anti-tumoural activities against pleural malignancies and concluded that its anti-tumoural activity against mesothelioma warrants clinical validation.20 Finally, a very attractive treatment strategy, stem cell therapy, was recently introduced in an editorial published in Respirology.21 It has been reported that cellular therapy using stem cells may constitute a major component of future therapies. Pleural procedures such as thoracentesis and chest drain insertion are commonly performed worldwide. Complications, including iatrogenic pneumothorax, bleeding and re-expansion pulmonary oedema, may occur although probably at a lower rate than previously thought. In a 3.5-year audit of 529 bedside procedures using safety checklists, and ultrasound-guidance in 86% of the cases, the complication rate was only 3% and was similar whether being performed by either pulmonologist or non-pulmonologist operators.22 The presence of COPD independently increased the risk of complications by nearly sevenfold. In another large series of 9320 ultrasound-guided thoracenteses, the overall complication rate (0.98%) and pneumothorax rate (0.61%) was also lower than many published studies.23 Specifically, the incidence of re-expansion pulmonary oedema was extremely low (0.01%). Recently, an intriguing preliminary observation of cough-related changes in pleural pressure during therapeutic thoracentesis in three patients showed that elevation of pleural pressure not only coincided with coughing episodes but persisted shortly thereafter.24 Thus, the authors hypothesized that cough might have a beneficial effect preventing the excessive drop in pleural pressure. Determination of epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogen homologue (KRAS) mutational status, as well as anaplastic lymphoma kinase rearrangement, has become an essential part of the evaluation of lung cancer patients because of its prognostic and therapeutic implications. Obtaining tissue samples for this purpose is often difficult, whereas analysing pleural fluid is easy and less invasive. In a study of 57 patients with malignant pleural effusions (84% with lung cancer), detection of KRAS mutations by peptide nucleic acid clamping was higher in pleural fluid samples (14%) and their cellular blocks (16.7%) than in matched tumour tissues (5%) and serum (3.6%) specimens, thus reinforcing the suitability of the former for mutation analyses.25 An excellent review addressed the current controversies and trends in the management of malignant pleural effusions.26 The main goal when dealing with this condition should be to relieve patient's symptoms with the least invasive and cost-effective strategies, while reducing hospitalization time. Therapeutic thoracentesis, due to its temporary benefits, is indicated in patients with: (i) very short expected survival (e.g. ≤4 weeks) or poor performance status; (ii) potential multifactorial causes of breathlessness in order to establish the relative contribution of the effusion to this symptom; and (iii) tumours in which a favourable short-term response to targeted therapies or chemotherapy is expected (eg. small cell lung cancer, lung cancer with EGFR mutations, lymphoma). Even though the risk of re-expansion pulmonary oedema is extremely low, recommended fluid removal is generally limited to 1.5 L unless pleural pressure is monitored during the procedure. Pleurodesis and placement of an indwelling pleural catheter (IPC) are the common definitive procedures to control symptomatic malignant effusions, but the preferred choice is controversial.26 The ideal timing for pleurodesis, that is, whether it should be performed routinely at the diagnosis of malignant pleurisy or deferred until symptomatic recurrence occurs, has not been established. Talc poudrage pleurodesis through thoracoscopy has not demonstrated superiority over chest tube talc slurry.26 If talc is selected as the sclerosant agent, large particle size preparations are recommended to avoid the development of an acute respiratory distress syndrome. Finally, IPC allows the ambulatory drainage of malignant effusions with similar symptomatic benefits as pleurodesis. It is indicated either as a primary approach or when pleurodesis fails (up to 30%) or is unsuitable (trapped lung). The procedure has few minor complications (eg. catheter blockage, cellulitis, symptomatic loculation) and spontaneous pleurodesis ensues in almost half the patients at an average time of 2 months, a situation in which IPC is definitely removed.26 Future treatment strategies for malignant pleural effusions should encompass advances in translational and experimental medicine. For example, one study evaluated the anti-tumoural effects of a S. aureus bio-product which has been used as a pleurodesing agent.19 This commercially available compound killed mesothelial cells in vitro and retarded tumour growth in a murine model of mesothelioma. A review described the role of interventional pulmonology in the management of bacterial infections of the pleural space.27 All patients with community-acquired parapneumonic effusions or empyema should receive empirical antibiotics covering Gram-positive cocci and anaerobes, but usually not atypical bacterial pathogens such as Legionella or Mycoplasma. The optimal duration of antibiotic therapy is unknown, although a period of 4 to 6 weeks is not uncommon.27 Nutritional supplementation is advised if poor nutrition is a concern. A decision on whether to drain non-purulent effusions is challenging and generally based on radiological (large effusions) and pleural fluid biochemical (low pH or glucose) or microbiological (positive Gram stains or cultures) data. As there are no randomized controlled studies offering guidance, it may be wise to follow the recommendation of Dr Light in initially performing a therapeutic rather than a diagnostic thoracentesis.28 The rationale is that if no fluid re-accumulates, no additional therapy will be necessary. Alternatively, when indicators for pleural drainage exist, small-bore chest drains placed under ultrasound guidance are the procedure of choice.27 The rightful place for intrapleural fibrinolytics remains a matter of intense debate. Meta-analyses of randomized controlled trials that have included the negative First Multicenter Intrapleural Sepsis Trial 1 (MIST1) and second MIST2 studies still conclude that urokinase or alteplase might be potentially effective for reducing the need for surgery.29 According to MIST2 study, the administration of alteplase and DNase intrapleurally should be considered whenever patients, particularly those who are not good surgical candidates, fail to respond to thoracostomy drainage. Surgical (i.e. video-assisted thoracoscopic surgery or open thoracotomy) rather than medical thoracoscopy is favoured when sepsis is uncontrolled despite the previously instituted therapies or when lung entrapment develops as a complication of the pleural infection. A systematic review reported the clinical characteristics and treatment of patients with yellow-nail syndrome (YNS).30 It is probably an acquired disease affecting lymphatic drainage, which is diagnosed when at least two of the following three characteristics are met: yellow nails, lymphoedema and chronic respiratory symptoms including pleural effusions in 40–50% of the cases. The authors compiled 150 YNS patients with pleural effusions.30 The median age was 60 years, without gender predominance. All patients had lymphoedema, yet 14% did not exhibit yellow nails. Pleural effusions were bilateral in two thirds, had a serous appearance in 75% of the cases and milky in 20%, and met exudative criteria with lymphocytic predominance in 95%. On pleural biopsy, findings were either unspecific or consistent with chronic pleuritis. For symptomatic persistent effusions, pleurodesis or decortication/pleurectomy is effective in most cases. Acute respiratory infection is a major cause of morbidity and mortality among children, especially in developing countries. In a study by Wu et al.31 in Hubei, China, indirect immunofluorescence assays for immunoglobulin M antibodies were positive in 7046 (67.5%) of 10 435 serum specimens collected from hospitalized children presenting with acute respiratory infection symptoms against at least one of the following nine pathogenic viruses and atypical bacteria: Mycoplasma virus respiratory virus Legionella and had the highest detection rate followed by virus and respiratory virus for hospitalization and diagnostic criteria for study might have to the high detection As many as specimens were positive for at least two an of the in current and of the profile with their specific and age may still to the clinical management of children hospitalized for acute respiratory infection. et al. the potential role of acute a common disease of in the of Acute in has been associated with an increased risk of the primary However, it remains whether acute to the subsequent development of or it the clinical in to between various and viral is to be by in different of these may important prognostic and to prevention treatment. In a by et al. studies with a total of patients, the positive negative and diagnostic odds of the receptor on for diagnosis of lower respiratory infection were and The overall diagnostic was similar for community-acquired and in but not was significantly by the method in analysis. for were in studies using different on either serum or fluid as the is a clinical studies are to the diagnostic utility of in different clinical Mycoplasma be diagnosed through clinical symptoms and in children and with community-acquired et al. reported findings on CT of the chest in of cases of infection with cough or more and a chest observation the sensitivity of chest in or due to An chest should not be to in children or presenting with acute respiratory A clinical risk using of 4 for for 2 for chronic and 1 for has previously been found to well at patients regarding their risk for S. aureus or in patients via the with bacterial et al. another risk for by potentially pathogens using of for 5 for 2 for and for the presence of other risk for The risk the in pathogens in the with among patients hospitalized with bacterial and in a subsequent with among similar patients. An optimal between sensitivity and specificity was at a low of A of or hospitalization may thus the for appropriate antibiotic against in the empirical treatment of bacterial The of from bacterial not to a clinically infection. In the study by et among patients with from respiratory specimens, was diagnosed by treatment or fluid in patients whereas with was diagnosed in another Patients with were independently associated with a of of more than radiological findings other than and a of or In a study by et of patients diagnosed of had of symptoms as by a time interval of over from to The time from to diagnosis was independently associated with previous and antibiotic therapy, and less While it was associated with a higher rate of there was less need for and no effect on has been shown to be a useful addition to the diagnostic for community-acquired A higher mortality was in as compared to but in a previous In a study by et al. patients for the performed the of showed a sensitivity of results were independently associated with a higher risk of treatment and thus prognostic of a positive in in presence of of to and duration of antibiotic treatment for acute respiratory infections has been shown to reduce antibiotic consumption without on treatment or mortality different clinical In a study by et serum was found to be an of mortality among to a with cough for 2 or more weeks in serum and could be into a prognostic model to patients with different mortality risks from variable to a model may be useful in identifying patients at high risk of from lower respiratory infections in low and HIV infection is In a study by et previous use of in patients hospitalized for was independently associated with a inflammatory response as by lower tumour factor but there was no on association persisted in a of patients with A previous study demonstrated a different inflammatory with a lower in among patients with COPD as compared to those but such was not and COPD therefore to inflammatory response in with potential on disease clinical treatment has also been associated with a lower incidence of parapneumonic effusion in patients with different chronic respiratory The clinical of pulmonary is often to In an study by et al. a total of pulmonary patients in the size of decreased in and increased in another on serial chest CT during a median follow-up duration of 1 was associated with higher more and was associated with size of and of prognostic markers are in patients with and infection. et al. a retrospective of 52 with and pulmonary nodules and on at were found to be of chemotherapy was more to to as compared with patients with but there was no in survival. The has to be with as it is often to selection especially in to who to and when to in an et al. an using and to the role of an in the of a of on the and survival of in was found to be of to either or of with and the of thus to a role of the in the et al. evaluated the performance of microscopic observation in 173 samples collected from patients to have its time as compared to the the clinical utility of the was still

BACKGROUND: Malignant and paramalignant pleural effusions are important complications of many malignancies. The two main management options debated in the literature are: 1) insertion of an indwelling pleural catheter (IPC) to achieve chronic drainage of the effusion, or 2) hospitalization with tube thoracostomy and subsequent chemical pleurodesis (CP) with talc or doxycycline to prevent fluid reaccumulation. We aimed to describe a large series of patients with malignant pleural effusions managed with an IPC, identify and validate factors identified in the literature as predictors of spontaneous pleurodesis in the IPC group and compare the group managed with IPC to patients managed with CP. METHODS: We designed a retrospective cohort study comparing patients with malignant and paramalignant pleural effusions managed either with CP between March 1, 2003 and February 28, 2006 or IPC insertion between May 1, 2006 and April 1, 2009. The CP group was identified through the prescription of talc or doxycycline and the IPC group from the IPC clinic database. Data were collected from paper and electronic records and from the Government of Ontario. RESULTS: We identified 193 consecutive patients with an ECOG performance status of less than 4 (ECOG less than 4 means that the patient is not completely disabled and confined to bed or chair) having undergone IPC insertion and 168 who were managed with CP. None of the variables we tested were significant predictors of spontaneous pleurodesis in the IPC group. Pleural effusion control rates at 6 months were higher in the IPC group than in the CP

Pleural diseases are a frequent health problem and most clinical studies to date focused on generation of successful treatments for pleural diseases without considering patients9 opinion for their symptomatic relief. Patients-related outcome measures (PROMs) should be objectively assessed and guide interventions. In our study we estimated PROMs after pleural interventions. We prospectively collected data from 124 patients (12/2013-2/2015). Pleural interventions included diagnostic-therapeutic aspiration, medical thoracoscopy, intercostal chest drain (ICD) and indwelling pleural catheter (IPC) insertion. We gathered information for pain, dyspnea, expected improvement and willingness to repeat the procedure if needed by using a visual analogue scale (VAS). The results showed that the most painful procedure was medical thoracoscopy (VAS: 20 ± 20.3mms) whereas diagnostic aspiration (VAS: 2.52 ± 4.78mms) was the less uncomfortable. Pain measurements were similar in ICD and IPC insertion groups. VAS for dyspnoea demonstrated that intercostal drain insertion had the greatest effect in patients9 breathlessness compared to the other procedures (VAS difference pre and post-procedure: 50.8 ± 27mms). 99.8% of the patients would repeat any of the procedures. Our study demonstrates the significant effect of pleural procedures in PROMs. Interventions ought to be patient oriented and our study will lead to the addition of PROMs in future clinical studies in pleural diseases.

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Chest tube insertion is a common procedure usually done for the purpose of draining accumulated air or fluid in the pleural cavity. Small-bore chest tubes (≤14F) are generally recommended as the first-line therapy for spontaneous pneumothorax in non-ventilated patients and pleural effusions in general, with the possible exception of hemothoraces and malignant effusions (for which an immediate pleurodesis is planned). Large-bore chest drains may be useful for very large air leaks, as well as post-ineffective trial with small-bore drains. Chest tube insertion should be guided by imaging, either bedside ultrasonography or, less commonly, computed tomography. The so-called trocar technique must be avoided. Instead, blunt dissection (for tubes >24F) or the Seldinger technique should be used. All chest tubes are connected to a drainage system device: flutter valve, underwater seal, electronic systems or, for indwelling pleural catheters (IPC), vacuum bottles. The classic, three-bottle drainage system requires either (external) wall suction or gravity (“water seal”) drainage (the former not being routinely recommended unless the latter is not effective). The optimal timing for tube removal is still a matter of controversy; however, the use of digital drainage systems facilitates informed and prudent decision-making in that area. A drain-clamping test before tube withdrawal is generally not advocated. Pain, drain blockage and accidental dislodgment are common complications of small-bore drains; the most dreaded complications include organ injury, hemothorax, infections, and re-expansion pulmonary edema. IPC represent a first-line palliative therapy of malignant pleural effusions in many centers. The optimal frequency of drainage, for IPC, has not been formally agreed upon or otherwise officially established.

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. 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. 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. 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.

205 Background: Indwelling pleural catheter (IPC) placement is an alternative to chemical pleurodesis for malignant pleural effusion (MPE), a complication of advanced cancer. In 1997 an IPC was approved which uses vacuum bottles (VB) for drainage (PleurX, Becton, Dickinson and Company, Franklin Lakes, NJ), and later another IPC system, which employs a manually operated vacuum pump (VP) for drainage (Aspira, Bard Access Systems, Salt Lake City, UT). Most studies comparing IPC versus chemical pleurodesis used the VB IPC. In clinical practice VB and VP are used interchangeably. We conducted a single-center retrospective study to compare the efficacy and safety of these two IPC systems. Methods: With Institutional Review Board approval, we recorded baseline characteristics and outcomes in patients with MPE who received an IPC in our hospital from January 2013 to March 2015. Results: 27 patients were found (median age 59 years, range 30-92). ECOG performance status was 3-4 in 24 (89%); mean ±SD albumin, 2.49 ± 0.48g/dL; median respiratory rate 24 breaths / minute (range 18-40); median heart rate 106 beats / minute (range 59 – 138). A palliative care consultation was requested in 14 (52%) patients. Cancer was of lung (9 patients, 33%), breast (8, 30%), gastrointestinal (4, 15%), hematological (2, 7%), gynecological (2, 7%), prostate (1, 4%) and melanoma (1, 4%). Pleural fluid was exudate in 24 (89%); cytology malignant in 8 (31%). Six patients (22%) received chemotherapy with IPC in situ. VP group (VPG) consisted of 18 (67%) patients and the VB group (VBG) of 9 (33%), with similar characteristics. Spontaneous pleurodesis and IPC removal were achieved in 4 patients (22%) in VPG, 3 (33%) in VBG. Additional pleural procedures were required in 6 (33%) of VPG and 2 (22%) of VBG. Median length of stay was 9 days (range 2 – 38) in VPG, 13 days (range 4-32) in VBG. Catheter-related complications (pain, obstruction, infection, hemorrhage) rate was 39% (7 patients) in VPG and 33% (3 patients) in VBG; no death was caused. Intergroup differences were not statistically significant. Conclusions: In our sample, symptom palliation was achieved in all patients; efficacy and safety were similar for either type of IPC. More studies are needed for further comparisons.

Background Indwelling pleural catheters (IPCs) are used to manage recurring effusions in patients with symptomatic malignant pleural effusion (MPE). A subset of these patients will have had previous failed talc pleurodesis. This study aims to look at the rate of autopleurodesis (and the time to achieve this) in IPC patients who had received previous talc compared to those who had not. Methods All IPC insertion records for MPE between 2008 and April 2017 were analysed retrospectively. Data on previous ipsilateral pleural procedures, including attempted talc pleurodesis performed prior to the IPC insertion, and details about IPC insertion outcomes were collected from the medical records. Autopleurodesis was defined as minimal or no output via IPC, with subsequent IPC removal. Results 181 IPC insertions for MPEs were recorded, but 2 insertions were excluded due to insufficient data about IPC removal date and reason for removal (n=179 analysed further). 68 patients (38%) had received prior talc (60 received talc once; 8 received talc twice); while 111 (62%) had not received prior talc. IPC was subsequently removed due to autopleurodesis in 23 of the 68 (33.8%) who had received prior talc after a median 105 days (IQR 91) (an additional IPC was removed because of pain 4 days after insertion). IPC was subsequently removed due to autopleurodesis in 37 of the 111 (33.3%) who had not received prior talc after a median 104 days (IQR 83.5) (3 more IPCs removed in this group for other reasons). There was no difference in rates of autopleurodesis between patients who had received prior talc and those who had not (X2 0.0045, p=0.946). When comparing time to autopleurodesis, there was no statistically significant difference between the 2 groups (2 tailed Mann Whitney test, p=0.29). Conclusion There does not seem to be a difference in the rate of autopleurodesis between patients who had previous failed talc pleurodesis and those who chose IPC in the first instance. Further studies are needed to investigate whether the pleural space in certain patients is inherently resistant to different forms of pleurodesis.

Interventions for the management of malignant pleural effusions: a network meta-analysis.