Australasian Malignant PLeural Effusion (AMPLE)-4 trial: study protocol for a multi-centre randomised trial of topical antibiotics prophylaxis for infections of indwelling pleural catheters.

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.

Tracheobronchial stents: an expanding prospect.

The first dedicated tracheobronchial silicone stent was designed by the French pulmonologist Jean-Paul Dumon. The most common indications for stenting are to minimise extrinsic airway compression from mass effect, maintain airway patency due to intrinsic obstruction or treat significant nonmalignant airway narrowing or fistulae. Silicone stents require rigid bronchoscopy for insertion; however, they are more readily repositioned and removed compared with metallic stents. Metallic stents demonstrate luminal narrowing when loads are applied to their ends, therefore stents should either be reinforced at the ends or exceed the area of stenosis by a minimum of 5 mm. Nitinol, a nickel-titanium metal alloy, is currently the preferred material used for airway stents. Airway stenting provides effective palliation for patients with severe symptomatic obstruction. Drug-eluting and three-dimensional printing of airway stents present promising solutions to the challenges of the physical and anatomical constraints of the tracheobronchial tree. Biodegradable stents could also be a solution for the treatment of nonmalignant airway obstruction.

Endobronchial indocyanine green instillation to identify the intersegmental plane for successful segmentectomy.

The traditional indications for lobectomy for resectable Non-small Cell Lung Cancer (NSCLC) may be set to change. Recently, anatomical segmentectomy (AS) versus lobectomy as an approach for early-stage NSCLC has been described in phase 3 randomised controlled trials. The demand for methods to facilitate AS may increase as a consequence. We describe three cases of AS using the combination of endobronchial infiltration of indocyanine green (ICG) to identify the intersegmental plane (critical for the performance of AS), and Computed Tomography (CT) guided methylene blue injection for lesion localisation. The operations were completed successfully demonstrating satisfactory post-operative outcomes including lesion resection with clear surgical margins and acceptable length of stay. We believe that endobronchial instillation of ICG and CT-guided methylene blue injection for lesion localisation show promise as a technique to complement parenchymal sparing thoracic oncological surgery.

Reversal of collateral ventilation using endoscopic polymer foam in COPD patients undergoing endoscopic lung volume reduction with endobronchial valves: A controlled parallel group trial.

BACKGROUND AND OBJECTIVE: We have previously described reversal of collateral ventilation (CV) in a severe chronic obstructive pulmonary disease (COPD) patient with endoscopic polymer foam (EPF), prior to endoscopic lung volume reduction (ELVR) with valves. The aim of this study was to investigate the efficacy of this in a larger cohort and compare outcomes with a similar cohort with no CV. METHODS: Patients with severe COPD, with the left upper lobe (LUL) targeted for ELVR, were assessed for CV with high resolution computed tomography (HRCT). If fissure completeness was >95% they were enrolled as controls for valves alone (endobronchial valve control group [EBV-CTRL]). If fissure completeness was 80%-95%, defects were mapped to the corresponding segment, where EPF was instilled following confirmation of CV with CHARTIS. EBVs were inserted 1 month afterwards. RESULTS: Fourteen patients were enrolled into both arms. After 6 months, there were significant improvements in both groups in forced expiratory volume in 1 s (FEV1; +19.7% EPF vs. +27.7% EBV-CTRL, p < 0.05); residual volume (RV; -16.2% EPF vs. -20.1% EBV-CTRL, p = NS); SGRQ (-15.1 EPF vs. -16.6 EBV-CTRL p = NS) and 6 min walk (+25.8% EPF [77.2 m] vs. +28.4% [82.3 m] EBV-CTRL p = NS). Patients with fissural defects mapped to the lingula had better outcomes than those mapped to other segments (FEV1 +22.9% vs. +16.3% p < 0.05). There were no serious adverse reactions to EPF. CONCLUSION: EPF successfully reverses CV in severe COPD patients with a left oblique fissure that is 80%-95% complete. Following EBV, outcomes are similar to patients with complete fissures undergoing ELVR with EBV alone. EPF therapy to reverse CV potentially increases the number of COPD patients suitable for ELVR with minimal adverse reactions.

Australasian Malignant PLeural Effusion (AMPLE)-3 trial: study protocol for a multi-centre randomised study comparing indwelling pleural catheter (±talc pleurodesis) versus video-assisted thoracoscopic surgery for management of malignant pleural effusion.

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.

Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): A Pilot Randomized Clinical Trial.

Rationale: Pleural effusion commonly complicates community-acquired pneumonia and is associated with intense pleural inflammation. Whether antiinflammatory treatment with corticosteroids improves outcomes is unknown. Objectives: To assess the effects of corticosteroids in an adult population with pneumonia-related pleural effusion. Methods: The STOPPE (Steroid Therapy and Outcome of Parapneumonic Pleural Effusions) trial was a pilot, multicenter, double-blinded, placebo-controlled, randomized trial involving six Australian centers. Patients with community-acquired pneumonia and pleural effusion were randomized (2:1) to intravenous dexamethasone (4 mg twice daily for 48 h) or placebo and followed for 30 days. Given the diverse effects of corticosteroids, a comprehensive range of clinical, serological, and imaging outcomes were assessed in this pilot trial (ACTRN12618000947202). Measurements and Main Results: Eighty patients were randomized (one withdrawn before treatment) and received dexamethasone (n = 51) or placebo (n = 28). This pilot trial found no preliminary evidence of benefits of dexamethasone in improving time to sustained (>12 h) normalization of vital signs (temperature, oxygen saturations, blood pressure, heart, and respiratory rates): median, 41.0 (95% confidence interval, 32.3-54.5) versus 27.8 (15.4-49.5) hours in the placebo arm (hazard ratio, 0.729 [95% confidence interval, 0.453-1.173]; P = 0.193). Similarly, no differences in C-reactive protein or leukocyte counts were observed, except for a higher leukocyte count in the dexamethasone group at Day 3. Pleural drainage procedures were performed in 49.0% of dexamethasone-treated and 42.9% of placebo-treated patients (P = 0.60). Radiographic pleural opacification decreased over time with no consistent intergroup differences. Mean duration of antibiotic therapy (22.4 [SD, 15.4] vs. 20.4 [SD, 13.8] d) and median hospitalization (6.0 [interquartile range, 5.0-10.0] vs. 5.5 [interquartile range, 5.0-8.0] d) were similar between the dexamethasone and placebo groups. Serious adverse events occurred in 25.5% of dexamethasone-treated and 21.4% of placebo-treated patients. Transient hyperglycemia more commonly affected the dexamethasone group (15.6% vs. 7.1%). Conclusions: Systemic corticosteroids showed no preliminary benefits in adults with parapneumonic effusions. Clinical trial registered with www.anzctr.org.au (ACTRN12618000947202).

Interventional bronchoscopy for chronic obstructive pulmonary disease: more than a pipe dream.

Endoscopic lung volume reduction (ELVR) is recognised in both national and international expert guidelines as one of the few additive treatments to benefit patients with advanced chronic obstructive pulmonary disease (COPD) who are otherwise receiving optimal medical and supportive care. Despite these recommendations and a growing evidence base, these procedures are not widely offered across Australia and New Zealand, and general practitioner and physician awareness of this therapy can be improved. ELVR aims to mitigate the impact of hyperinflation and gas trapping on dyspnoea and exercise intolerance in COPD. Effective ELVR is of proven benefit in improving symptoms, quality of life, lung function and survival. Several endoscopic techniques to achieve ELVR have been developed, with endobronchial valve placement to collapse a single lobe being the most widely studied and commonly practised. This review describes the physiological rationale underpinning lung volume reduction, highlights the challenges of patient selection, and provides an overview of the evidence for current and investigational endoscopic interventions for COPD.

Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial.

Rationale: Chronic bronchitis (CB) is characterized by productive cough with excessive mucus production, resulting in quality-of-life impairment and increased exacerbation risk. Bronchial rheoplasty uses an endobronchial catheter to apply nonthermal pulsed electrical fields to the airways. Preclinical studies have demonstrated epithelial ablation followed by regeneration of normalized epithelium.Objectives: To evaluate the feasibility, safety, and initial outcomes of bronchial rheoplasty in patients with CB.Methods: Pooled analysis of two separate studies enrolling 30 patients undergoing bilateral bronchial rheoplasty was conducted. Follow-up through 6 months (primary outcome) and 12 months included assessment of adverse events, airway histology, and changes in symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test and St. George's Respiratory Questionnaire (SGRQ).Measurements and Main Results: Bronchial rheoplasty was performed in all 30 patients (63% male; mean [SD] age, 67 [7.4]; mean [SD] postbronchodilator FEV1, 65% [21%]; mean [SD] COPD Assessment Test score 25.6 [7.1]; mean [SD] SGRQ score, 59.6 [15.3]). There were no device-related and four procedure-related serious adverse events through 6 months, and there were none thereafter through 12 months. The most frequent nonserious, device- and/or procedure-related event through 6 months was mild hemoptysis in 47% (14 of 30) patients. Histologically, the mean goblet cell hyperplasia score was reduced by a statistically significant amount (P < 0.001). Significant changes from baseline to 6 months in COPD Assessment Test (mean, -7.9; median, -8.0; P = 0.0002) and SGRQ (mean, -14.6; median, -7.2; P = 0.0002) scores were observed, with similar observations through 12 months.Conclusions: This study provides the first clinical evidence of the feasibility, safety, and initial outcomes of bronchial rheoplasty in symptomatic patients with CB.Clinical trial registered with www.anzctr.org.au (ACTRN 12617000330347) and clinicaltrials.gov (NCT03107494).

Pleural Cryobiopsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural biopsy using either video-assisted thoracoscopic surgery or medical pleuroscopy is the current diagnostic criterion standard for pleural pathology with a high, yet imperfect, diagnostic yield. Cryobiopsy may provide greater tissue, increase depth of sampled tissue, and/or reduce crush artifact. However, its impact on diagnostic yield remains uncertain, and there are potential concerns regarding its safety too. We performed a systematic review and meta-analysis to investigate the same. METHODS: We performed a systematic search of MEDLINE, Embase, and Google Scholar for studies evaluating the performance of pleural cryobiopsy, assessing the quality of each study using the Quality Assessment, Data Abstraction and Synthesis-2 tool. Using inverse variance weighting, we performed a meta-analysis of diagnostic yield estimations. We also reviewed specimen characteristics and complications related to the procedure. RESULTS: Seven observational studies involving 586 pleural biopsies (311 cryobiopsies and 275 flexible forceps biopsies) were evaluated. All but one study used a semi-rigid thoracoscope. Meta-analysis generated a diagnostic yield of 96.5% for cryobiopsy and 93.1% for forceps biopsy with an inverse variance-weighted OR of 1.61 (95% CI, 0.71-3.66) and an I2 of 16%. No instances of moderate to severe bleeding were reported with cryobiopsy. A funnel plot illustrated no major publication bias. CONCLUSIONS: Based on analysis of relatively homogenous observational data, pleural cryobiopsy is safe but does not increase diagnostic yield over flexible forceps biopsy. Adequately powered multicenter randomized trials are needed for further investigation.

Transbronchial Cryobiopsy in Interstitial Lung Disease: Safety of a Standardized Procedure.

BACKGROUND: Transbronchial lung cryobiopsy (TBCB) plays an increasing role in the evaluation of diffuse parenchymal lung disease with acceptable diagnostic yield and safety profile compared with that of video-assisted thoracoscopic surgical lung biopsy on most reports. However, published outcomes with regard to safety and complication rates vary. We aim to determine the safety profile of TBCB when performed using a standardized protocol consistent with recently published expert guidelines. MATERIALS AND METHODS: We reviewed prospectively maintained databases from 5 Australian tertiary referral centers. The procedures were performed in accordance with a recent expert statement recommending standardization of TBCB procedures, in particular with fluoroscopy, a secured airway, and prophylactic bronchial blockers. Periprocedural complications were assessed along with clinical outcomes. RESULTS: A total of 121 patients underwent TBCB between August 2013 and August 2017 following a standardized protocol using general anesthesia. Of them, 84 patients (66.7%) were discharged on the day of the procedure. Pneumothorax occurred in 18 patients (14.9%), 13 (10.7%) of whom required chest tube drainage. Moderate bleeding occurred in 15 patients (13.2%) and severe bleeding in 1 (0.83%). Histopathologic diagnosis was made in 80 patients (66.1%). CONCLUSION: Pooled outcomes from Australian tertiary centers indicate that TBCB is safe when performed in a protocolized fashion. Active measures to anticipate and manage bleeding and to direct biopsy position result in low rates of major complications.

Management of recurrent haemoptysis in malignancy with combined TISSEEL and intrabronchial valves.

Management of recurrent haemoptysis poses a difficult clinical scenario. TISSEEL (Baxter Healthcare Corporation Deerfield, IL, USA) is a fibrin sealant often used in surgery to aid control of bleeding. However, when endoscopic TISSEEL is used independently, migration, dislodgement, or even expectoration of the fibrin clot is a common complication that may lead to recurrence of haemoptysis. Here we describe two patients with recurrent haemoptysis in the context of malignancy who underwent bronchoscopy, during which they were managed with application of topical TISSEEL to the bleeding area, followed by deployment of an intrabronchial valve, followed by a further application of TISSEEL over the valve. The combination of TISSEEL and intrabronchial valve appeared to control haemoptysis and was resistant to expectoration or migration in these two cases. Thus, this combination may provide a safe and effective therapeutic option for the control of bronchial bleeding secondary to malignancy.

Laparoscopic adjustable gastric banding - under-diagnosed late respiratory complications.

With the current epidemic of obesity in Australia, bariatric surgery has become increasingly accessible for patients with a body mass index above 35 kg/m². Laparoscopic adjustable gastric banding (LAGB) is currently the weight loss surgery of choice for its perceived simplicity and its low peri-operative complication and mortality rates. The short term complications and long term benefits of sustained weight loss with LAGB are well described but the medium term respiratory complications are less clearly appreciated. We report three cases with LAGB who presented with significant respiratory tract symptoms to the Nepean Hospital in New South Wales, a teaching hospital with a busy LAGB service, during the period from January to March 2012.