Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Costal margin injuries and trans-diaphragmatic intercostal hernia: Presentation, management and outcomes according to the Sheffield classification.

BACKGROUND: Costal margin rupture (CMR) injuries are under-diagnosed and inconsistently managed, while carrying significant symptomatic burden. We hypothesized that the Sheffield Classification system of CMR injuries would relate to injury patterns and management options. METHODS: Data were collected prospectively between 2006 and 2023 at a major trauma center in the United Kingdom. Computed tomography scans were interrogated and injuries were categorized according to the Sheffield Classification. Clinical, radiologic, management and outcome variables were assessed. RESULTS: Fifty-four patients were included in the study. Intercostal hernia (IH) was present in 30 patients and associated with delayed presentation ( p = 0.004), expulsive mechanism of injury (i.e. such as occurs with coughing, sneezing, or retching), higher body mass index ( p < 0.001), and surgical management ( p = 0.02). There was a bimodal distribution of the level of the costal margin rupture, with IH Present and expulsive mechanism injuries occurring predominantly at the ninth costal cartilage, and IH Absent cases and other mechanisms at the seventh costal cartilage ( p < 0.001). There were correlations between the costal cartilage being thin at the site of the CMR and the presence of IH and expulsive etiology ( p < 0.001). Management was conservative in 23 and surgical in 31 cases. Extrathoracic mesh IH repairs were performed in 3, Double Layer Mesh Repairs in 8, Suture IH repairs in 5, CMR plating in 8, CMR sutures in 2, and associated Surgical Stabilization of Rib Fractures in 11 patients. There was one postoperative death. There were seven repeat surgical procedures in five patients. CONCLUSION: The Sheffield Classification is associated statistically with presentation, related chest wall injury patterns, and type of definitive management. Further collaborative data collection is required to determine the optimal management strategies. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

The everlasting issue of prolonged air leaks after lobectomy for non-small cell lung cancer: A data-driven prevention planning model in the era of minimally invasive approaches.

BACKGROUND AND OBJECTIVES: Prolonged air leaks (PAL) are the most frequent complication after lobectomy for non-small cell lung cancer, even in case of minimally invasive approaches. We developed a novel score to identify high-risk patients for PAL during minimally invasive lobectomy. METHODS: A dedicated database was created. We investigated preoperative candidate features and specific intraoperative variables. Univariate and subsequent logistic regression analysis with bootstrap resampling have been used. Model performance has been assessed by reckoning the area under the receiver operating characteristics curve and the Hosmer-Lemeshow goodness of fit. RESULTS: PAL (>5 days) occurred in 72 (15.69%) patients. Five variables emerged from the model. Each one was assigned a score to provide a cumulative scoring system: forced expiratory volume in 1 second below 86% (P = 0.004, 1.5 points), body mass index <24 ( P = 0.002, 1 point), active smoking ( P = 0.001, 1.5 points), incomplete fissures ( P = 0.004, 1.5 points), and adhesions ( P = 0.0001, 1 point). The new score provided a stratification into four risk classes. CONCLUSIONS: The risk score incorporates either general or more specific variables, providing a risk stratification that could be readily applied intra- and postoperatively. Henceforth, specific technical and management measures could be properly allocated to curb PAL.

Evaluation of surgical approaches to anatomical segmentectomies: the transition to minimal invasive surgery improves hospital outcomes.

BACKGROUND: We aim to evaluate the transition process from open to video-assisted thoracoscopic surgery (VATS) anatomical segmentectomies in a regional thoracic surgical unit. METHODS: In a retrospective study from January 2013 to December 2015, we identified all anatomical segmentectomies performed in our unit. Pre, peri and postoperative data were compared between the three years (2013, 2014 and 2015) and according to operative approach. Thoracotomy after VATS intraoperative biopsy was considered a conversion for the purposes of the study. RESULTS: A total of 86 consecutive cases [56 females and 30 males, median age 70 years (range, 43 to 83 years); median FEV1 of 78% predicted (range, 41% to 126%)] were included. There was a significant change in the surgical approach with time. Fifty-two cases underwent VATS (73% via single-port) and 34 open surgeries, including nine conversions. There were no postoperative deaths in the VATS group and one in the open group. Operative outcomes were similar over time with no haemorrhagic events, equivalent R1 resection and nodal stations explored in all lymph node positive patients. In node negative cases however, open surgery was associated with more extensive mediastinal exploration. Patients in 2015 had a shorter hospital stay in comparison to those in previous years [median 4 days (range, 1-15 days) vs. median 6 days (range, 3-27 days), P=0.01]. There were no differences in the incidence of complications or readmissions to hospital over time. CONCLUSIONS: The transition over a short period of time from open to single-port VATS segmentectomy has allowed us to significantly reduce postoperative hospital stay without compromising operative or postoperative outcomes.

The influence of prior multiport experience on the learning curve for single-port thoracoscopic lobectomy: a multicentre comparative study†.

OBJECTIVES: Competency in video-assisted thoracoscopic (VATS) lobectomy is estimated to be reached after the surgeon completes 50 cases. We wanted to explore the impact of competency in performing multiport VATS lobectomies on completing the needed number of single-port VATS. METHODS: In a retrospective multicentre study, 6 individual surgeons (3 with previous competency in multiport VATS lobectomy and 3 without) submitted their first 50 cases of single-port VATS lobectomies. Extended and sublobar resections were excluded. Pre-, peri- and postoperative data were compared between the groups of surgeons. Chi-square and Wilcoxon's rank tests were used. The less experienced surgeons had previously attended dedicated training courses and visited with experts. RESULTS: A total of 300 cases were included [150 in Group A (surgeons with previous experience performing multiport VATS) and 150 in Group B (surgeons without extensive experience performing multiport VATS)]. Surgeons in Group B performed significantly more elective open lobectomies during their learning curve period than surgeons of Group A (58 vs 1). Patients in Group B were older and had more risk factors. There were 3 in-hospital deaths (respiratory failure, sepsis and fatal stroke). There were no differences between the groups in operative time, intensive care unit admissions, hospital stay, total complications, tumour size or number of N2 stations explored. Only the duration of intercostal drainage (2 vs 3 days, 0.012), incidence of respiratory tract infections (1% vs 7%, P = 0.002) and conversion rates (4% vs 12%, P = 0.018) were better in Group A. Patients characteristics played a role in the development of respiratory infections and longer drainage times but not in the need for conversion. CONCLUSIONS: Overall, postoperative outcomes during the learning curve period for single-port VATS lobectomies are not noticeably affected by previous multiport VATS experience. Less experienced surgeons were more selective in order to achieve competency (more lower lobectomies and more open operations). Competency in single-port VATS lobectomy can be acquired safely with adequate training and good case selection but will be achieved 'faster' with previous competency in multiport VATS lobectomy.

Determining optimal fluid and air leak cut off values for chest drain management in general thoracic surgery.

BACKGROUND: Chest drain duration is one of the most important influencing aspects of hospital stay but the management is perhaps one of the most variable aspects of thoracic surgical care. The aim of our study is to report outcomes associated with increasing fluid and air leak criteria of protocol based management. METHODS: A 6-year retrospective analysis of protocolised chest drain management starting in 2007 with a fluid criteria of 3 mL/kg increasing to 7 mL/kg in 2011 to no fluid criteria in 2012, and an air leak criteria of 24 hours without leak till 2012 when digital air leak monitoring was introduced with a criteria of <20 mL/min of air leak for more than 6 hours. Patient data were obtained from electronic hospital records and digital chest films were reviewed to determine the duration of chest tube drainage and post-drain removal complications. RESULTS: From 2009 to 2012, 626 consecutive patients underwent thoracic surgery procedures under a single consultant. A total of 160 did not require a chest drain and data was missing in 22, leaving 444 for analysis. The mean age [standard deviation (SD)] was 57±19 years and 272 (61%) were men. There were no differences in the incidence of pneumothoraces (P=0.191), effusion (P=0.344) or re-interventions (P=0.431) for drain re-insertions as progressively permissive criteria were applied. The median drain duration dropped from 1-3 days (P<0.001) and accordingly hospital stay reduced from 4-6 days (P<0.001). CONCLUSIONS: Our results show that chest drains can be safely removed without fluid criteria and air leak of less than 20 mL/min with median drain duration of 1 day, associated with a reduced length of hospital stay.

Uniportal thoracoscopic management of middle lobe torsion after upper lobectomy.

Lobar torsion is a rare but potentially life-threatening complication following pulmonary resection. Surgical management usually entails an exploratory thoracotomy and resection of the involved lobe if nonviable. We present the case of a 67-year-old woman diagnosed with right middle lobe torsion 5 days after thoracotomy and right upper lobectomy for squamous carcinoma of the lung. A thoracoscopic right middle lobectomy was successfully performed utilizing a single 4-cm port placed along the midaxillary line in the 5th intercostal space.

Completing the audit cycle improves surgical standards in lung cancer. Why do some patients still not receive the best care?

INTRODUCTION: Intraoperative gold standards in the management of lung cancer include performing anatomical resection and mediastinal lymphadenectomy). Our aim was to measure improvement in quality of surgery by reauditing anatomical resection and lymph node excision in patients undergoing lung cancer surgery as per gold standards. METHODS: A complete audit cycle was performed-an initial retrospective analysis of 100 consecutive patients with primary lung cancer operated on by a single surgeon (July 2009-October 2010), followed by a prospective reaudit of 102 patients (November 2010-October 2011). Clinical and pathological data were collected from clinical notes, surgical database, and histopathology reports. Univariate and multivariate analyses were performed to identify further areas of potential improvement. RESULTS: The number of nonanatomical resections dropped from 12% to 6% (p = not significant). The rate of performing excision of at least 1, 2, and 3 mediastinal (N2) lymph node stations improved from 86% to 91%, 63% to 77%, and 40% to 63%, respectively (p = 0.003). On multivariate analysis, failure to perform anatomical resection was related to use of video assisted thoracic surgery (VATS) techniques, previous malignancy, and high-predicted surgical risk by European Society Objective Score .01. Less complete intraoperative lymph node excision was associated with cases performed by VATS and in octogenarians. CONCLUSIONS: There is continued adherence to the guidelines, when considering cases in terms of anatomical resections, and marked improvement in complying with the gold standards for lymph node excision. The use of the audit tool has contributed to improved quality of surgical care in patients operated for lung cancer.

The left thoracotomy approach for excision of distal tracheal carcinoma in the presence of right-sided aorta.

Tracheal primary carcinoma is a rare malignancy, and we believe that its presence in a patient with a right-sided aorta has not been described before. We report a case of a primary tracheal squamous carcinoma in a patient with a four-branched right-sided aortic arch. The patient underwent a tracheal resection approached by a left thoracotomy. The surgical exposure was excellent once the ligamentum arteriosum had been divided. All the aortic arch branches and the phrenic, vagus and recurrent laryngeal nerves were identified and preserved.

Initial experience with the use of biological implants for soft tissue and chest wall reconstruction in thoracic surgery.

BACKGROUND: Synthetic materials have traditionally been used for tissue reconstruction in thoracic surgery. New biomaterials have been tested in other areas of surgery with good results. The aim of our study is to evaluate our initial experience using prostheses in extended thoracic surgery. METHODS: A review was performed of all patients who underwent extended surgical procedures requiring soft tissue reconstruction with bioprosthetic materials after thoracic surgery from August 2009 to August 2011. A total of 44 consecutive patients were included. Operations involved radical pleurectomy and decortication for mesothelioma (n = 29), extended operations for thoracic malignancies (n = 8), surgery for trauma or perforated organs or complications (n = 6), and for benign infectious causes (n = 1). RESULTS: A total of 76 patches were used in 44 patients (median of 2; range 1 to 3 per patient). Median hospital stay was 13 (range 5 to 149) days. Three patients died during the postoperative period (6.8%); pulmonary embolism 5 days after intrapericardial pneumonectomy with chest wall reconstruction, fatal pneumonia 26 days after radical pleurectomy and decortication for mesothelioma, and bronchopleural fistula 11 days after pneumonectomy with diaphragm and atrium excision for lung cancer after initial chemoradiotherapy. No other surgical exploration or removal of patches has been required for infection. CONCLUSIONS: Our initial experience of using bioprosthetic patches for soft tissue reconstruction in thoracic surgery has proven satisfactory with overall acceptable results. The infection rates are low even when a proportion of procedures were performed under contaminated environments. Biologic prosthesis should be part of the surgical options to reconstruct soft tissues in thoracic surgery.

Accuracy of two scoring systems for risk stratification in thoracic surgery.

We investigate the suitability of the two existing risk stratification systems available for predicting mortality in a cohort of patients undergoing lung resection under a single surgeon. Data from the 290 consecutive patients who underwent pulmonary resection between January 2008 and January 2011 were extracted from a prospective clinical data base. In-hospital mortality risk scores are calculated for every patient by using Thoracoscore and ESOS.01 and were compared with actual in-hospital mortality. The receiver operating characteristic (ROC) curve was used to establish how well the systems rank for predicting patient mortality. Actual in-hospital mortality was 3.1% (n = 9). Thoracoscore and ESOS values (mean ± SEM) were 4.93 ± 0.32 and 4.08 ± 0.41, respectively. The area under the ROC curve values for ESOS and Thoracoscore were 0.8 and 0.6, respectively. ESOS was reasonably accurate at predicting the overall mortality (sensitivity 88% and specificity 67%), whereas Thoracoscore was a weaker predictor of mortality (sensitivity 67% and specificity 53%). The ESOS score had better predictive values in our patient population and might be easier to calculate. Because of their low specificity, the use of these scores should be limited to the assessment of outcomes of surgical cohorts, but they are not designed to predict risks for individual patients.

Prospective external convergence evaluation of two different quality-of-life instruments in lung resection patients.

OBJECTIVES: The interpretation of studies on quality of life (QoL) after lung surgery is often difficult owing to the use of multiple instruments with inconsistent scales and metrics. Although a more standardized approach would be desirable, the most appropriate instrument to be used in this setting is still largely undefined. The aim of the study was to assess the respective ability of two validated QoL instruments (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30/L13 and Short Form (36) Health Survey (SF-36)) to detect perioperative changes in QoL of patients submitted to pulmonary resection for non-small-cell lung cancer (NSCLC). METHODS: A prospective study on 33 consecutive patients (May 2009-December 2009) was submitted to pulmonary resection. All patients completed both EORTC QLQ-C30 with lung module 13 and SF-36 pre- and postoperatively (3 months). Preoperative changes of all SF-36 and EORTC scales were assessed by using the Cohen's effect-size method. External convergence between different instruments (SF-36 vs EORTC) was assessed by measuring the correlation of scales evaluating the same concepts (physical, psychosocial, and emotional). The correlation coefficients between standardized perioperative changes (effect sizes) of objective functional parameters (forced expiratory volume in 1s (FEV1) and diffusion lung capacity for carbon monoxide (DLCO)) and SF-36 or EORTC scales were also investigated. RESULTS: A poor correlation (r < 0.5) was detected between most of the scales of the two instruments measuring the same QoL concepts, indicating that they may be complementary in investigating different aspects of QoL. Only the SF-36 and EORTC social functioning scales and the SF-36 mental health and EORTC emotional functioning scales had a correlation coefficient >0.5. In general, EORTC was more sensitive in detecting physical or emotional declines but was more conservative in detecting improvements. Both SF-36 and EORTC showed poor correlations (r < 0.5) between perioperative changes in QoL and FEV1 or DLCO, confirming that objective parameters cannot be surrogates to the subjective perception of QoL. In particular, there was a poor correlation between perceived changes in dyspnea and objective changes in FEV1 or DLCO. CONCLUSIONS: EORTC behaved similarly to SF-36 in assessing perioperative changes in generic QoL scales, but, with the use of its lung module, provided a more detailed evaluation of specific symptoms. For this reason, EORTC should be regarded as the instrument of choice for measuring QoL in the thoracic surgery setting.

Short-term perioperative treatment with ambroxol reduces pulmonary complications and hospital costs after pulmonary lobectomy: a randomized trial.

OBJECTIVE: To assess in a randomized clinical trial the influence of perioperative short-term ambroxol administration on postoperative complications, hospital stay and costs after pulmonary lobectomy for lung cancer. METHODS: One hundred and forty consecutive patients undergoing lobectomy for lung cancer (April 2006-November 2007) were randomized in two groups. Group A (70 patients): ambroxol was administered by intravenous infusion in the context of the usual therapy on the day of operation and on the first 3 postoperative days (1000 mg/day). Group B (70 patients): fluid therapy only without ambroxol. Groups were compared in terms of occurrence of postoperative complications, length of stay and costs. RESULTS: There were no dropouts from either group and no complications related to treatment. The two groups were well matched for perioperative and operative variables. Compared to group B, group A (ambroxol) had a reduction of postoperative pulmonary complications (4 vs 13, 6% vs 19%, p=0.02), and unplanned ICU admission/readmission (1 vs 6, 1.4% vs 8.6%, p=0.1) rates. Moreover, the postoperative stay and costs were reduced by 2.5 days (5.6 vs 8.1, p=0.02) and 2765 Euro (2499 Euro vs 5264 Euro, p=0.04), respectively. CONCLUSIONS: Short-term perioperative treatment with ambroxol improved early outcome after lobectomy and may be used to implement fast-tracking policies and cut postoperative costs. Nevertheless, other independent trials are needed to verify the effect of this treatment in different settings.

Peak oxygen consumption during cardiopulmonary exercise test improves risk stratification in candidates to major lung resection.

BACKGROUND: The objective of this investigation was to assess the association of peak oxygen consumption (Vo(2)) with postoperative outcome in a prospective cohort of patients undergoing major lung resection for the treatment of lung cancer. METHODS: Preoperative symptom-limited cardiopulmonary exercise testing (CPET) performed using cycle ergometry was conducted in 204 consecutive patients who had undergone pulmonary lobectomy or pneumonectomy. Peak Vo(2) was tested for possible association with postoperative cardiopulmonary complications and mortality. Logistic regression analysis, validated by a bootstrap analysis, was used to adjust for the effect of other perioperative factors. The role of peak Vo(2) in stratifying the surgical risk was further assessed in different groups of patients subdivided according to their cardiorespiratory status. RESULTS: Logistic regression showed that peak Vo(2) was an independent and reliable predictor of pulmonary complications (p = 0.04). All six deaths occurred in patients with a peak Vo(2) of < 20 mL/kg/min (four deaths in patients with a peak Vo(2) of < 12 mL/kg/min). The mortality rate in this high-risk group was 10-fold higher (4 of 30 patients; 13%) compared to those with higher peak Vo(2) (p = 0.006). Compared to patients with a peak Vo(2) of > 20 mL/kg/min, those with a peak Vo(2) of < 12 mL/kg/min had 5-fold, 8-fold, 5-fold, and 13-fold higher rates, respectively, of total cardiopulmonary complications pulmonary complications, cardiac complications, and mortality. CONCLUSIONS: The present study supports a more liberal use of CPET before lung resection compared to the current guidelines since this test can help in stratifying the surgical risk and optimizing perioperative care.

Computational patient-specific models based on 3-D ultrasound data to quantify uterine arterial flow during pregnancy.

Information on uterine blood flow rate during pregnancy would widely improve our knowledge on feto-placental patho-physiology. Ultrasonographic flow rate evaluation requires the knowledge of the spatial velocity profiles throughout the investigated vessel; these data may be obtained from hemodynamic simulations with accurate computational models. Recently, computational models of superficial vessels have been created using 3-D ultrasound data; unfortunately, common reconstruction methods are unsuitable for the uterine arteries due to the low quality achievable of imaged deep vessels. In this paper a simplified spline-based technique was applied to create computational models for patient-specific simulations of uterine arterial heamodynamics. Moreover, a novel method to quantify the uterine flow rates was developed based on echo-Doppler measurements and computational data. Preliminary results obtained for four patients indicated a quite narrow range for the blood flow rate through the main uterine artery with large variability in the flow split between corporal and cervical branches. Furthermore, parabolic-like velocity profiles were obtained in the branching region of the different patients, suggesting a clinical use of averaged, not patient-specific, spatial velocity distribution coefficients for the blood flow rate calculation. The developed reconstruction method based on 3-D ultrasound imaging is efficient for creating realistic custom models of the uterine arteries. The results of the fluid dynamic simulations allowed us to quantify the uterine arterial flow and its repartition in normal pregnancies.