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.

A case of malignant mesothelioma in a young patient with childhood leukaemia who had received total body irradiation.

This case report explores a 34-year-old male diagnosed with mesothelioma who had no known risk factors. The patient initially was treated for empyema with antibiotics but later represented to hospital with worsening symptoms. He underwent a surgical Video-assisted thoracoscopic surgery procedure and lung biopsy, which revealed a diagnosis of mesothelioma. The young age of the patient as well as absence of significant risk factors for mesothelioma made the diagnosis unexpected. The patient had total body irradiation (TBI) therapy for leukaemia as a child, which increases the risk of developing cancer. However, there are limited studies exploring the risk of pleural mesothelioma post-TBI. Young patients who represent to hospital, with limited response to initial treatment, and suspicious radiological features should be considered for lung biopsy to reduce the risk of a missed diagnosis. Patients with a background of TBI should also be considered for follow-up to monitor for any subsequent malignancy.

Clinical Outcomes and Return to Sports After Open Reduction and Hamstring Tendon Autograft Reconstruction in Patients With Acute Traumatic First-Time Posterior Dislocation of the Sternoclavicular Joint.

BACKGROUND: Traumatic posterior dislocations of the sternoclavicular joint (SCJ) are rare. Multiple case reports, case series, and systematic reviews have been published on the treatment of posterior SCJ dislocations. However, they have usually been of small numbers, described a variety of surgical techniques on a mixture of acute and chronic dislocations, and have not focused on functional recovery or return to sports. PURPOSE/HYPOTHESIS: The purpose of this study was to assess the clinical outcomes and return to sports after SCJ open reduction and reconstruction using a hamstring tendon autograft in patients with an acute first-time traumatic posterior dislocation of the SCJ. We hypothesized that SCJ open reduction and reconstruction would result in high survivorship, good clinical outcomes, and a high rate of return to sports. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This study included all patients who underwent SCJ open reduction and reconstruction within 14 days of sustaining a first-time traumatic posteriorly dislocated SCJ, with a minimum 3-year follow-up. Patient-reported outcomes were assessed by the following scores: short version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH), Rockwood SCJ, modified Constant, and Single Assessment Numeric Evaluation (SANE). Survivorship was defined as no clinical failure, such as instability or recurrent dislocation, and no revision surgery. Return to sports was assessed using a customized questionnaire. RESULTS: A total of 19 patients who underwent surgery were included, with a mean age of 30.8 years (range, 18-52 years). Seventeen patients were available at final follow-up at a mean 94.5 months (range, 37-155 months). At final follow-up, the mean scores were as follows: QuickDASH, 4.3 (range, 0-20.4); Rockwood, 13.9 (range, 12-15); modified Constant, 94.4 (range, 71-100); and SANE, 92.1 (range, 70-100). The construct survivorship was 96%. Of the 14 patients who participated in sports, 12 (86%) returned to their preinjury levels. CONCLUSION: After an acute first-time traumatic posterior SCJ dislocation, open reduction and stabilization with a hamstring tendon autograft, undertaken within 14 days of injury, provides good clinical outcomes and high rates of survivorship and return to sports.

Subxiphoid, Nonintubated, Opioid-Free, Video-Assisted Pneumonectomy: A New Frontier in Thoracic Surgery.

Surgical approaches to major pulmonary resections have evolved from thoracotomy to multiportal video-assisted thoracoscopy (VATS) and subsequently uniportal VATS. The efficacy of this progress has been validated in a multitude of publications demonstrating reductions in complications, patient perception of pain, and postoperative length of stay. More recent advances include subxiphoid extrathoracic access and nonintubated, opioid-free anesthesia. Early publications have demonstrated promising results with respect to safety, technical feasibility, and enhanced recovery. However, there remains a paucity of literature relating to hybrid approaches comprising both subxiphoid and nonintubated, opioid-free anesthesia in the context of pneumonectomy. The current report is the case of a patient undergoing pneumonectomy. Both subxiphoid and nonintubated, opioid-free techniques were utilized. The authors describe preoperative workup, surgical and anesthesia-related caveats, and postoperative recovery. In conclusion, this approach is technically feasible, safe, and may be associated with enhanced recovery.

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.

Uniportal subxiphoid bilateral removal of self-introduced thoracic foreign bodies.

This is a report of a 31-year-old male refugee, who was admitted to Intensive Therapy Unit after being found in severe chest pain after escaping extreme torture from his home country. He was found to have four nails in his thorax. These were removed using a subxiphoid video-assisted thorascopic surgery (VATS) technique. This technique allowed excellent visualization of the right, left and anterior mediastinal part of the chest and therefore preventing damage or injury to surrounding structures. This was particularly useful in a complex case such as this. By avoiding an intercoastal incision and intercostal manipulation, our patient had limited pain post-procedure facilitating an earlier aggressive mobilization program with potential benefit in terms of improved lung expansion, reduction of atelectasis and lung infections. With the right training, the technical challenges of using the technique should be overcome and thus the benefits of subxiphoid VATS will be offered to a larger portion of thoracic surgical patients.

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.

A hypercoagulable state leading to venous limb gangrene associated with occult lung adenocarcinoma.

We report a case of lung adenocarcinoma-associated hypercoagulability leading to venous limb gangrene, managed successfully with argatroban and then dabigatran. Use of idarucizumab permitted diagnostic investigations, leading to targeted antineoplastic therapy with crizotinib, surgical resection with curative intent, and continued survival over 2 years after the index event.

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.

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.

The role of EBUS-TBNA and standard bronchoscopic modalities in the diagnosis of sarcoidosis.

BACKGROUND AND AIMS: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is an accurate and minimally invasive technique that has been shown to have excellent diagnostic yield in the diagnosis of mediastinal and hilar lymphadenopathy. However, endoscopic bronchial biopsy (EBB) and transbronchial lung biopsy (TBLB) are still the standard method for making a pathologic diagnosis of sarcoidosis. The aim of this study was to compare the diagnostic yield of EBUS-TBNA and TBLB through a flexible bronchoscope in patients with stage I and II sarcoidosis. METHODS: A total of 653 patients with suspected stage I and II sarcoidosis were included in this retrospective study. After radiological assessment, patients were qualified to bronchoscopy. Patients underwent sequential EBUS-TBNA followed by TBLB and/or EBB. In all patients, 1056 biopsies from mediastinal lymph nodes group were taken. RESULTS: In all of the biopsied lymph nodes, positive results were obtained in 549 patients (84%). In 180 patients with stage II TBLB, a biopsy was taken from affected part of the lung. Positive results were found in 79 patients (43.9%). EBB was performed in 340 patients, with a positive result in 101 (29.7%). Mediastinoscopy was performed in 60 patients (9.2%) with a negative result in EBUS-TBNA, TBLB and/or EBB. Non-caseating granulomas were found in 48 patients. The sensitivity of TBLB technique alone was significantly lower at 43.9% (79/180) (P < 0.001). The sensitivity of EBB was significantly lower than EBUS-TBNA and TBLB and reached 29.7% (101/340) (P < 0.0001, P < 0.003). The overall diagnostic accuracy for EBUS-TBNA was 84%, and the combination of EBUS-TBNA with standard bronchoscopic techniques had a diagnostic accuracy of 89%. CONCLUSION: The diagnostic yield of the EBUS-TBNA for stage I and II sarcoidosis is clearly higher than for TBLB and EBB. The combination of EBUS-TBNA with standard bronchoscopic techniques is safe and feasible, and optimizes the diagnostic yield in patients with pulmonary sarcoidosis and enlarged intrathoracic lymph nodes. EBUS-TBNA in combination with standard bronchoscopy may be considered to be the first-line investigation in patients with suspected sarcoidosis and enlarged intrathoracic lymphadenopathy.

Subxiphoid approach for spontaneous bilateral pneumothorax: a case report.

The development of video-assisted thoracoscopic surgery (VATS) has contributed to reduced pain and improved recovery following thoracic surgery. However, pain remains a major issue. Patients with bilateral pulmonary pathology requiring operative intervention may have even more pain due to bilateral transthoracic incisions. The recently described uniportal subxiphoid VATS approach provides an opportunity to undertake bilateral thoracic surgery through a single incision that avoids the bilateral intercostal nerve damage caused by transthoracic incision and drainage. Here we report a case of a patient requiring bilateral bullectomy and pleurectomy for the management of pneumothorax that was performed successfully by the subxiphoid VATS approach.

Subxiphoid single incision thoracoscopic surgery approach for thymectomy: a case report.

Thoracic surgery is rapidly evolving with minimally invasive strategies now dominating. Thymectomy has traditionally been performed through a sternotomy, but more recently video-assisted thoracoscopic surgery (VATS) approaches have become increasingly popular. To further minimise surgical impact, the uniportal subxiphoid VATS technique has recently been described, using a muscle sparing incision that avoids intercostal nerve injury. A potential advantage that makes this approach particularly suited to thymectomy includes the ability to access both sides of the chest with a single incision. There is also the potential for reduced post-operative pain and chronic thoracostomy neuralgia. Here we describe the management of a patient with thymoma, reporting our procedure and technique for performing uniportal subxiphoid VATS thymectomy.

Evaluation of the diagnostic utility of endobronchial ultrasound-guided transbronchial needle aspiration for metastatic mediastinal tumors.

BACKGROUND AND OBJECTIVES: The mediastinum is a relatively uncommon site of distant metastases, which typically appear as peripheral lung nodules. We chose to assess the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of distant metastases to the mediastinum. MATERIALS AND METHODS: Over the period 2008-2013, a total of 446 patients with concurrent or previously diagnosed and treated extrathoracic malignancies were evaluated. RESULTS: Surgical treatment was carried out in 414 patients (156 women and 237 men aged 26-68 years, mean age of 56.5 years) presenting with distant metastases to the lungs: Thoracoscopic wedge resection was completed in 393 patients and lobectomy and segmentectomy were performed in 7 and 14 patients, respectively. The median time from primary tumor resection was 6.5 years (range: 4.5 months to 17 years). Thirty-two of these patients underwent EBUS-TBNA for mediastinal manifestation of the underlying disease. EBUS-TBNA specimens were aspirated from the subcarinal or right paratracheal lymph node stations in 26 (81%) patients and from the hilar lymph nodes in 6 (18.8%) patients only. Metastases to lymph nodes were confirmed in 14 of these patients (43.8%). Primary lung cancer was diagnosed in seven patients. Mediastinoscopy was performed in two patients to reveal either lymph node metastasis or sarcoidosis. Thoracotomy for pulmonary metastases resection and mediastinal lymph node biopsy was performed in nine patients. Lymph node metastasis was confirmed in five patients (15.6%). The diagnostic efficacy, sensitivity, specificity, and negative predictive value (NPV) of EBUS-TBNA were 78.8%, 93.3%, 100%, and 87.5%, respectively. CONCLUSION: EBUS-TBNA is a valuable diagnostic tool in a selected group of patients with secondary tumors in the mediastinum and lungs.

Endobronchial ultrasound-guided transbronchial needle aspiration in the staging of lung cancer patients.

OBJECTIVE: Mediastinoscopy as diagnostic procedure for evaluation of mediastinum in patients with non-small-cell lung cancer has long been considered the reference standard. However, less invasive method has occurred. Endobronchial ultrasound-guided transbronchial needle aspiration came into widespread use and has resulted in controversy as to whether it is a good replacement for mediastinoscopy. We chose to demonstrate the usefulness of endobronchial ultrasound-guided transbronchial needle aspiration in evaluating the mediastinum in patients with non-small-cell lung cancer. MATERIAL AND METHODS: Over a 48-month period, 1841 patients underwent endobronchial ultrasound-guided transbronchial needle aspiration at our healthcare centre. In all patients, 2964 biopsies from the lymph node group N2 and 783 from group N1 were taken. The mean short axis of the lymph nodes biopsied was 2.0 (range: 0.6-2.6). The mean number of lymph node stations biopsied per patient was 2.6. Patients with a negative result of endobronchial ultrasound-guided transbronchial needle aspiration underwent mediastinoscopy. All patients with a negative result in endobronchial ultrasound-guided transbronchial needle aspiration and mediastinoscopy underwent surgical resection with lymph node sampling. RESULTS: The metastases to lymph nodes N2/N3 and N1 were found in 1111 (60.3%) and 199 (9.3%), respectively. Mediastinoscopy was performed in 730 patients with a positive result in 83 (11.4%) patients. In the group of operated patients, metastatic N1 disease was found in 264 (14.1%). In the group of the operated patients, mediastinal involvement of disease (N2) was found in 30 patients (4.5%). The sensitivity, negative predictive value and diagnostic accuracy for hilar lymph node staging for endobronchial ultrasound-guided transbronchial needle aspiration were 57%, 96% and 96%, respectively. The sensitivity, negative predictive value and diagnostic accuracy per patient for mediastinal lymph node staging for endobronchial ultrasound-guided transbronchial needle aspiration and mediastinoscopy were 91%, 85%, 93% and 73%, 95.5%, 97%, respectively. The specificity and positive predictive value of both tests were 100%. CONCLUSION: The clinical usefulness of endobronchial ultrasound-guided transbronchial needle aspiration is undeniable according to diagnostic performance data. Endobronchial ultrasound-guided transbronchial needle aspiration should be considered complementary to mediastinoscopy in the evaluation of patients with radiographically abnormal mediastinum.