Single-cell transcriptomic analysis of human pleura reveals stromal heterogeneity and informs in vitro models of mesothelioma.

The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies. Here, we present the first comprehensive single-cell transcriptomic atlas of the human parietal pleura and demonstrate its utility in elucidating pleural biology. We confirm the presence of known universal fibroblasts and describe novel, potentially pleural-specific, fibroblast subtypes. We also present transcriptomic characterisation of multiple in vitro models of benign and malignant mesothelial cells, and characterise these through comparison with in vivo transcriptomic data. While bulk pleural transcriptomes have been reported previously, this is the first study to provide resolution at the single-cell level. We expect our pleural cell atlas will prove invaluable to those studying pleural biology and disease. It has already enabled us to shed light on the transdifferentiation of mesothelial cells, allowing us to develop a simple method for prolonging mesothelial cell differentiation in vitro.

Multicentre evaluation of renal impairment in thoracic surgery (MERITS): a retrospective cohort study.

OBJECTIVES: To measure the unit-level variation in Acute Kidney Injury (AKI) incidence post-thoracic surgery over a contemporary 1-year period. Secondary aims include examining the associations with sex, age group, operation type, length of stay and mortality. DESIGN: A multicentre, observational, retrospective study in thoracic surgery. SETTING: 17 of 35 Society for Cardiothoracic Surgery of Great Britain and Ireland (SCTS) units participated. The student wing, known as SCTS STUDENTS, supported data collection. PARTICIPANTS: Overall, 15 229 patients were collected of which 15 154 were included for analysis after exclusions. All patients (age≥18 years) undergoing any thoracic surgery from 1 April 2016 to 31 March 2017 were included. For analysis, we excluded patients with preoperative end-stage renal failure and those with incomplete data. MAIN OUTCOME MEASURES: The primary outcome is the incidence of AKI within 7 days of the procedure or discharge date if earlier. Secondary outcomes include assessing associations with patient demographics (age, sex), type of procedure (open and minimally invasive), length of stay and mortality. RESULTS: Out of 15 154 patients AKI was diagnosed in 1090 patients (7.2%) within 7 days of surgery with AKI stage 1 (4.8%), stage 2 (1.7%) and stage 3 (0.7%). There was a statistically significant variation in AKI incidence between units from 3.1 to 16.1% (p<0.05). Significant differences between AKI and non-AKI were found in post-operative length of stay (7 vs 3 days, p<0.001), 30-day mortality (9 vs 1.6%, p<0.001), 90-day mortality (14.7 vs 4.4%, p<0.001) and 1-year mortality (23.1 vs 12.2 %, p<0.001). CONCLUSIONS: Following thoracic surgery, AKI incidence ranged from 3.1% to 16.1% between units (p<0.05) with associations between AKI and both length of stay and mortality. We propose AKI as a suitable comparative and absolute quality measure in thoracic surgery. Reducing rates of AKI may improve patient outcomes, length of stay and reduce costs.

Opioid-Free Anesthesia for Lung Cancer Resection: A Case-Control Study.

OBJECTIVE: To assess the feasibility and effectiveness of an opioid-free anesthesia (OFA) technique in lung cancer resection surgery versus standard opioid-based techniques. DESIGN: Retrospective, propensity-matched, case-control study. SETTING: A single, specialty cardiothoracic center between January 2018 and July 2019. PARTICIPANTS: Adult patients undergoing lung cancer resection surgery. INTERVENTIONS: A cohort of 83 patients undergoing an OFA technique (OFA group) for lung cancer resection surgery was matched with 83 patients who underwent similar surgery with a standard anesthesia technique (STD group). Outcome measures compared between the 2 groups included postoperative pain scores at 0, 1, and 24 hours; 24-hour postoperative morphine patient-controlled analgesia consumption; recovery room and hospital lengths of stay; and 30-day all-cause mortality. MEASUREMENT AND MAIN RESULTS: No difference was found in median pain scores (interquartile range [IQR]) at 0 hours: STD 0 (0-1), OFA 0 (0-1); p = 0.48. Median pain scores (IQR) at 1 hour were statistically significantly greater in the STD group compared with the OFA group: STD 1 (0-1), OFA 0 (0-1); p = 0.03. There was no difference in median pain scores (IQR) at 24 hours: STD 0 (0-1), OFA 0 (0-1); p = 0.49. Mean postoperative 24-hour patient-controlled analgesia morphine consumption (standard deviation) was similar between groups: STD 21.1 (±18.8) mg, OFA 16.2 (±18.1) mg; p = 0.16. There was no difference in mean time spent in the postoperative recovery (standard deviation) area between the 2 groups: STD 116 (±49) minutes, OFA 108 (±34) minutes; p = 0.27. Median hospital length of stay (IQR) was longer in the STD group compared with the OFA group: STD 4 (2-6) days, OFA 3 (2-4) days; p = 0.002. CONCLUSIONS: This case-control study demonstrated that an OFA technique in lung cancer resection surgery offers a feasible and safe approach, resulting in similar postoperative pain scores and morphine consumption compared with standard opioid-containing techniques.

Surgical Management of Thoracic Multiple Exostoses.

Hereditary multiple exostoses is a rare autosomal dominant condition resulting in the development of multiple osteochondromas. We present the case of a 25-year-old woman with hereditary multiple exostoses who was referred for thoracic surgery assessment due to severe right-sided chest pain. Computed tomographic scan allowed preoperative planning for resection of the lesion. Under general anesthesia, right video-assisted thoracoscopic surgery was performed through a cosmetic retromammary incision. Complete removal of the tumor resolved symptoms, and she was discharged 2 days later. We show that video-assisted thoracoscopic surgery with a cosmetically placed muscle-sparing incision allowed accurate resection with faster recovery.

Acute kidney injury after thoracic surgery: a proposal for a multicentre evaluation (MERITS).

OBJECTIVES: Because the mortality rate is very low in thoracic surgery, its use as a quality discriminator is limited. Acute kidney injury (AKI) is a candidate measure because it is associated with increased rates of morbidity and mortality and is partly preventable. The incidence of AKI after thoracic surgery is not well documented. We conducted an audit to determine the incidence and outcomes of AKI. This audit became a pilot project, and the results indicate the feasibility of a larger study. METHODS: Retrospective data on renal function post-thoracic surgery were collected at a tertiary cardiothoracic unit over 12 months. Renal impairment was classified according to the Kidney Disease Improving Global Outcomes criteria. RESULTS: Of 568 patients (mean = 59 ± SD 18; 38% women), AKI was diagnosed in 86 (15.1%) within 72 h post-thoracic surgery based on the Kidney Disease Improving Global Outcomes staging system (stage 1, n = 55; stage 2, n = 25; stage 3, n = 6). Significant differences were found in postoperative length of stay (3 vs 5 days; P < 0.001) of patients with and without AKI. There was a significant difference between the age groups of patients with and without AKI (P < 0.05) in the open surgical group but not in the group having video-assisted thoracoscopic surgery (VATS). There was no significant difference in the mortality rates between patients with and without AKI. CONCLUSIONS: The incidence of AKI after thoracic surgery was 15.1%. AKI was associated with longer hospital stays and was more likely in ≥60-year-old patients after open surgery than after VATS. Reducing AKI could improve patient outcomes. We propose that AKI may be a useful quality measure in thoracic surgery. We are developing a multicentre audit based on this approach.

MesoTRAP: a feasibility study that includes a pilot clinical trial comparing video-assisted thoracoscopic partial pleurectomy decortication with indwelling pleural catheter in patients with trapped lung due to malignant pleural mesothelioma designed to address recruitment and randomisation uncertainties and sample size requirements for a phase III trial.

Introduction: One of the most debilitating symptoms of malignant pleural mesothelioma (MPM) is dyspnoea caused by pleural effusion. MPM can be complicated by the presence of tumour on the visceral pleura preventing the lung from re-expanding, known as trapped lung (TL). There is currently no consensus on the best way to manage TL. One approach is insertion of an indwelling pleural catheter (IPC) under local anaesthesia. Another is video-assisted thoracoscopic partial pleurectomy/decortication (VAT-PD). Performed under general anaesthesia, VAT-PD permits surgical removal of the rind of tumour from the visceral pleura thereby allowing the lung to fully re-expand. Methods and analysis: MesoTRAP is a feasibility study that includes a pilot multicentre, randomised controlled clinical trial comparing VAT-PD with IPC in patients with TL and pleural effusion due to MPM. The primary objective is to measure the SD of visual analogue scale scores for dyspnoea following randomisation and examine the patterns of change over time in each treatment group. Secondary objectives include documenting survival and adverse events, estimating the incidence and prevalence of TL in patients with MPM, examining completion of alternative forms of data capture for economic evaluation and determining the ability to randomise 38 patients in 18 months. Ethics and dissemination: This study was approved by the East of England-Cambridge Central Research Ethics Committee and the Health Research Authority (reference number 16/EE/0370). We aim to publish the outputs of this work in international peer-reviewed journals compliant with an Open Access policy. Trial registration: NCT03412357.

Subxiphoid uniportal video-assisted thoracoscopic lung volume reduction surgery.

We present the case of a 50-year-old woman with severe emphysema, who underwent subxiphoid uniportal video-assisted lung volume reduction surgery. Standard techniques include staged unilateral video-assisted thoracoscopic surgery and historically sternotomy and thoracotomy. Concerns that the subxiphoid incision may have impacted on the abdominal component of ventilation was considered; however, this was not the case, and pain control was excellent. The patient was discharged home after 3 days with no chest drain. Lung function and performance status have improved considerably.

Long term and disease-free survival following surgical resection of occult N2 lung cancer.

BACKGROUND: Despite systematic investigation with computed tomography (CT), positron emission tomography (PET)/CT, CT or magnetic resonance imaging (MRI) brain imaging and supplementary investigation using endobronchial ultrasound guided biopsy (EBUS), endo-oesophageal ultrasound guided biopsy (EUS), fine needle aspiration (FNA), mediastinoscopy or mediastinotomy, there is an approximately 10% rate of occult N2 disease identified at pathological staging. It has been hypothesised that such occult disease, too small or inactive to be identified during pre-operative multi-modality staging, may represent low volume disease that may have equivalent survival to patients with similar stage at clinical, pre-operative assessment. We compared the long-term survival and disease-free survival of patients with the same clinical TNM stage with and without occult N2 disease. METHODS: We retrospectively analysed a database that prospectively captured information on all patients assessed and treated for lung cancer in our surgical unit. We reviewed data on patients who underwent lung cancer surgery with curative intent between January 2006 and August 2010. RESULTS: A total of 312 lung cancer resections were performed [mean age 68 (range, 42-86) years old and male:female ratio 1.14:1]. Occult N2 disease was identified in 28 (8.7%) of 312 patients. There was no difference in the rate of N2 disease for different tumour histological types. Five-year survival with occult N2 disease was 35.8% vs. 62.5% without. Median survival was 34 months with occult N2 disease vs. 84 months without. CONCLUSIONS: With contemporary staging techniques, so-called occult N2 disease, even with low volume and PET non-avid disease, does not have an indolent course and should still be considered a risk factor for poorer prognosis.

Robotic Camera Assistance: The Future of Laparoscopic and Thoracoscopic Surgery?

INTRODUCTION: Minimally invasive techniques have become the standard for a variety of procedures across all surgical specialties. There has been a recent move to integrate robotic technology into standard laparoscopic and thoracoscopic surgery with the aim of improving stability of the visual field with the use of robotic camera assistance. The aim of this study was to report on and examine the use of a headset-controlled robotic camera holder, FreeHand. METHODS: Between May 2013 and Dec 2016, 105 procedures were observed where the FreeHand robotic camera assistant was used. Observations were made of 43 consultant surgeons in 30 hospitals performing 21 different surgical procedures. During the surgery, the number of scope cleans and collisions were quantified, and surgeons were asked to score from 0 to 5 the setup, ergonomics, usability, and overall experience in a questionnaire. RESULTS: Overall surgeon satisfaction was rated as "good" for setup (4.29), ergonomics of the system (4.12), usability (4.39), and overall experience of the system (4.34). In 8 operations (7.6%), there was a conversion from robotic camera assistant to manual assistant. There were no reported adverse events attributable to the use of the system. CONCLUSION: This study demonstrates the breadth of surgical procedures that can be performed with a robotic camera assistant. The robotic camera assistant was found to be safe and simple to use and was positively perceived on assessment in multiple procedures spanning several surgical specialties. This work suggests that robotic camera assistants may offer significant benefits to laparoscopic and thoracoscopic surgeons.

The role of positron emission tomography in the diagnosis, staging and response assessment of non-small cell lung cancer.

Lung cancer is a common disease and the leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Following diagnosis of lung cancer, accurate staging is essential to guide clinical management and inform prognosis. Positron emission tomography (PET) in conjunction with computed tomography (CT)-as PET-CT has developed as an important tool in the multi-disciplinary management of lung cancer. This article will review the current evidence for the role of 18F-fluorodeoxyglucose (FDG) PET-CT in NSCLC diagnosis, staging, response assessment and follow up.

Hybrid video-assisted thoracoscopic surgery lobectomy and en-bloc chest wall resection for non-small cell lung cancer.

Chest wall invasion is seen in 5% to 8% of patients presenting with lung cancer. We report a case of complete resection of a 14 cm × 9 cm pT3N0M0 squamous cell carcinoma arising from the right lower lobe and invading the lower chest wall posteriorly, in a 75 years old male, via a hybrid thoracoscopic [video-assisted thoracoscopic surgery (VATS)] approach. Following conventional VATS lobectomy, a targeted 10 cm incision was performed to allow wide resection of the 7th to 10th ribs and 6th to 9th transverse processes, with the defect being subsequently reconstructed with a composite rigid prosthesis. The patient made an uneventful recovery, and was discharged on the 3rd postoperative day; with later adjuvant chemotherapy. Thoracoscopic surgery is not currently widely adopted in patients with chest wall invasion, likely due to the technical difficulties. We briefly review the various techniques described in the current literature, whilst emphasising a role for such an approach in highly selected cases.

A Randomized Controlled Trial of High-Flow Nasal Oxygen (Optiflow) as Part of an Enhanced Recovery Program After Lung Resection Surgery.

BACKGROUND: Patients undergoing thoracic surgery are at risk of postoperative pulmonary complications, which are associated with increased morbidity and mortality. High-flow nasal oxygen therapy delivers humidified, warmed positive airway pressure but has not been tested routinely after thoracic surgery. METHODS: We performed a randomized, controlled, blinded study. Patients undergoing elective lung resection were randomly assigned to either high-flow nasal oxygen or standard oxygen therapy. Patients were otherwise treated within an established enhanced recovery program. The primary outcome was the difference between the preoperative and postoperative 6-minute walk test. Secondary outcomes included hospital length of stay, spirometry, and patient-reported outcomes measured using the Postoperative Quality of Recovery Scale. RESULTS: Fifty-nine patients were randomly assigned to either high-flow nasal oxygen (n = 28) or standard oxygen (n = 31) therapy. We found no difference in the 6-minute walk test outcome or spirometry; however, length of hospital stay was significantly lower in the high-flow nasal oxygen group, median 2.5 days (range, 1 to 22), compared with the standard oxygen group, median 4.0 days (range, 2 to 18); geometric mean ratio was 0.68 (95% confidence interval: 0.48 to 0.86, p = 0.03). No significant differences in recovery domains were found, but patients in the high-flow nasal oxygen group reported significantly higher satisfaction (p = 0.046). CONCLUSIONS: Prophylactic high-flow nasal oxygen therapy, when incorporated into an enhanced recovery program, did not improve 6-minute walk test results but was associated with reduced length of hospital stay and improved satisfaction after lung resection, compared with standard oxygen. This finding has implications for reduced costs and better service provision, and a multicenter trial powered for length of stay is required.

Creative Use of Contralateral Combined Myocutaneous Free Flap for Empyema Cavity.

Treatment of chronic postpneumonectomy empyema is a reconstructive problem that is always complicated by previous thoracic surgical procedures. Free flaps may be used because they effectively obliterate remaining pleural cavity dead space. Combined muscle free flaps with common vascular pedicles are viable alternatives when single muscle flaps do not possess adequate bulk. This case describes a contralateral combined latissimus dorsi-serratus anterior myocutaneous free flap with anastomoses to thoracodorsal vessels used for correction of chronic empyema. We also describe successful correction of a posterolateral chest wall defect using the adjacent axillary system as a recipient vessel. An accompanying skin paddle also enabled reliable cutaneous coverage of the external defect.

Efficacy and cost of video-assisted thoracoscopic partial pleurectomy versus talc pleurodesis in patients with malignant pleural mesothelioma (MesoVATS): an open-label, randomised, controlled trial.

BACKGROUND: Malignant pleural mesothelioma incidence continues to rise, with few available evidence-based therapeutic options. Results of previous non-randomised studies suggested that video-assisted thoracoscopic partial pleurectomy (VAT-PP) might improve symptom control and survival. We aimed to compare efficacy in terms of overall survival, and cost, of VAT-PP and talc pleurodesis in patients with malignant pleural mesothelioma. METHODS: We undertook an open-label, parallel-group, randomised, controlled trial in patients aged 18 years or older with any subtype of confirmed or suspected mesothelioma with pleural effusion, recruited from 12 hospitals in the UK. Eligible patients were randomly assigned (1:1) to either VAT-PP or talc pleurodesis by computer-generated random numbers, stratified by European Organisation for Research and Treatment of Cancer risk category (high vs low). The primary outcome was overall survival at 1 year, analysed by intention to treat (all patients randomly assigned to a treatment group with a final diagnosis of mesothelioma). This trial is registered with ClinicalTrials.gov, number NCT00821860. FINDINGS: Between Oct 24, 2003, and Jan 24, 2012, we randomly assigned 196 patients, of whom 175 (88 assigned to talc pleurodesis, 87 assigned to VAT-PP) had confirmed mesothelioma. Overall survival at 1 year was 52% (95% CI 41-62) in the VAT-PP group and 57% (46-66) in the talc pleurodesis group (hazard ratio 1·04 [95% CI 0·76-1·42]; p=0·81). Surgical complications were significantly more common after VAT-PP than after talc pleurodesis, occurring in 24 (31%) of 78 patients who completed VAT-PP versus ten (14%) of 73 patients who completed talc pleurodesis (p=0·019), as were respiratory complications (19 [24%] vs 11 [15%]; p=0·22) and air-leak beyond 10 days (five [6%] vs one [1%]; p=0·21), although not significantly so. Median hospital stay was longer at 7 days (IQR 5-11) in patients who received VAT-PP compared with 3 days (2-5) for those who received talc pleurodesis (p<0·0001). INTERPRETATION: VAT-PP is not recommended to improve overall survival in patients with pleural effusion due to malignant pleural mesothelioma, and talc pleurodesis might be preferable considering the fewer complications and shorter hospital stay associated with this treatment. FUNDING: BUPA Foundation.

Adrenalectomy for isolated metastasis from operable non-small-cell lung cancer.

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'in [patients with isolated adrenal metastasis from operable/operated non-small cell lung cancer] is [adrenalectomy] superior [to chemo/radiotherapy alone for achieving long-term survival]?' Altogether >160 papers were found using the reported search, of which 3 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that the body of evidence is small, retrospective and not formally controlled. As such interpretation is limited by selection bias in assignment of patients. These limitations notwithstanding, surgical resection is associated with prolonged survival for patients with isolated adrenal metastasis from non-small cell lung cancer (NSCLC). Patient selection is probably critical. Factors that are important are: otherwise early tumour, node (TN) status of the lung primary and R0 resection, long disease-free interval and confidence that there are no other sites of metastasis. Patients with ipsilateral adrenal metastasis may derive the greatest survival benefit from adrenalectomy, since spread to the ipsilateral gland may occur via direct lymphatic channels in the retroperitoneum. Involvement of the contralateral adrenal may signify haematogenous spread and therefore, a more aggressive process. Adrenalectomy must be accompanied by regional lymph node clearance to reduce the chance of further spread from the adrenal itself.

Free deep inferior epigastric perforator flap used for management of post-pneumonectomy space empyema.

Various solutions exist for management of post-pneumonectomy space empyema. We describe the use of a free deep inferior epigastric perforator (DIEP) flap to fill the space and close a pleural window. Previously, flaps involving abdominal muscle or omentum have been used for this purpose. Abdominal surgery to harvest such flaps can impair ventilatory mechanics. The DIEP flap--harvested from the abdomen, and composed primarily of skin and muscle avoids this problem, thus is a desirable technique in patients with impaired lung function. We believe this is the first report of the DIEP flap to close a postpneumonectomy empyema space.

Benign emptying of postpneumonectomy space due to severe dehydration.

Causes of benign emptying of the postpneumonectomy space include small bronchopleural fistulas with spontaneous healing and escape of fluid into the chest wall or diaphragm. We present an additional cause: severe dehydration. As postpneumonectomy empyema usually involves drainage of the pleural space, it is important to be aware of this uncommon cause so as to avoid unnecessary instrumentation and contamination of the postpneumonectomy space.

What is the survival after surgery for localized malignant pleural mesothelioma?

A best evidence topic in thoracic surgery was written according to a structured protocol. This was with the purpose of assisting our management of patients with localized malignant mesothelioma of the pleura (LMM). Although the terminology is used inconsistently, this variant has been formally defined by the WHO as a distinct entity defined as localized disease histologically identical to the diffuse form but without any evidence of pleural spread. Treatments for LMM include different combinations of surgery, chemotherapy and radiotherapy. There is an impression that LMM may have a better outcome than the commoner diffuse form of malignant mesothelioma that has been reported to have a survival between 8 and 14 months. In order to advise our patients on prognosis, we studied the duration of survival after surgical resection of LMM. A total of 150 papers were found, of which 16 represented the best evidence to answer the question. The authors, journal, date, country of publication, study type, relevant outcomes and results of these papers are tabulated. It is difficult to combine the results of these 16 papers because both treatments and results are reported differently. Some report median survival (range: 11.6-36 months) and others disease-free survival (range: 0 months to 11 years). Median survival to the longest follow-up was 29 months when calculated by pooling data from informative papers using the Kaplan-Meier method. Our review suggests that survival in LMM is longer than that generally quoted for the more common diffuse form of malignant mesothelioma. Hence, aggressive treatment of LMM may be reasonable in appropriate patients.