Advances in the diagnosis and follow-up of pleural lesions: a scoping review.

INTRODUCTION: Pleural lesions may have heterogeneous presentation and causes. In recent years, there have been significant advances in pleural lesions diagnostics. The aim of this review is to provide an overview of the state-of-the-art, and recent updates for diagnostic modalities and monitoring regimes for pleural lesions. AREAS COVERED: A literature search was conducted through PubMed and Web of Science for relevant articles published from 1 January 2000, to 1 March 2023. The article critically appraises the radiological modalities and biopsy techniques that are employed in pleural lesions diagnostics, including chest radiography, thoracic ultrasound, computed tomography, F-fluorodeoxyglycose positron emission tomography, magnetic resonance imaging, percutaneous and thoracoscopic pleural biopsies with reference to their strengths, limitations and clinical use. The review asserts also the available literature regarding monitoring algorithms. EXPERT OPINION: Despite the recent advances in the field, there are several key areas for improvement, including the development and validation of minimal invasive methods and tools for risk stratification, the integration of multi-omics technologies, the implementation of standardized, evidence-based diagnostic and monitoring guidelines and increased focus on research and patient-centric approaches. The broad establishment of dedicated pleural clinics may significantly assist toward this direction.

In-hospital thromboprophylaxis variation and the risk of venous thromboembolism after lung cancer surgery: a nationwide cohort study.

OBJECTIVES: Venous thromboembolic event (VTE) is a severe complication in patients with lung cancer undergoing thoracic surgery. Nevertheless, because of insufficient evidence, there are no clear guidelines, and VTE prophylaxis practices vary widely. This nationwide cohort study was a comparative study investigating VTE risk in surgical departments that routinely administered in-hospital thromboprophylaxis with low-molecular-weight heparin compared to those that did not. METHODS: We identified all patients with non-small-cell lung cancer (NSCLC) who underwent surgery in Denmark during 2010-2021. Thoracic surgery was exclusively performed in the 4 university hospitals. Three hospitals implemented in-hospital thromboprophylaxis as standard care since 2000, while the fourth adopted this practice in September 2016. VTE events were assessed at 6-month follow-up according to hospital and study period, using an inverse probability of treatment weighting approach. RESULTS: We identified 9615 patients. During 6-month follow-up, a total of 190 VTE events were observed, resulting in a weighted rate of 4.5 events per 100 person-years and an absolute risk of 2.2%. There was no clear trend according to hospital site or use of in-hospital thromboprophylaxis with a 2.2% risk in the hospital not using thromboprophylaxis compared to 1.7-3.1% in those that did. CONCLUSIONS: Use of in-hospital thromboprophylaxis did not affect the risk of VTE after surgery for NSCLC, suggesting that relying solely on in-hospital thromboprophylaxis may be insufficient to mitigate VTE risk in these patients. Further research is warranted to investigate the potential benefits of extended thromboprophylaxis in reducing VTE risk in selected NSCLC surgical patients.

Risk of Venous Thromboembolism in Patients With Stage III and IV Non-Small-Cell Lung Cancer: Nationwide Descriptive Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non-small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments. MATERIALS AND METHODS: A nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen-Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy. RESULTS: Among the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis. CONCLUSION: VTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.

Complication rates rise with age and Haller index in minimally invasive correction of pectus excavatum: A high-volume, single-center retrospective cohort study.

OBJECTIVES: The study objectives were to describe the compounded complication rate of minimally invasive repair of pectus excavatum, identify predisposing risk factors, and evaluate the optimal timing of correction. Minimally invasive repair of pectus excavatum is the standard treatment for pectus excavatum and consists of 2 invasive procedures, for example, correction with bar insertion followed by bar removal after 2 to 3 years. METHODS: A retrospective cohort study identifying children, adolescents, and adults of both genders corrected for pectus excavatum with minimally invasive repair of pectus excavatum between 2001 and 2022. Information on complications related to bar insertion and removal procedures for each individual patient was compiled into a compounded complication rate. Complication severities were categorized according to the Clavien-Dindo classification. RESULTS: A total of 2013 patients were corrected by minimally invasive repair of pectus excavatum with a median age (interquartile range) for correction of 16.6 (5) years. Overall compounded complication rate occurred at a frequency of 16.4%, of which 9.3% required invasive reinterventions (Clavien-Dindo classification ≥IIIa). The complication rate related to bar insertion was 2.6-fold higher compared with bar removal (11.8% vs 4.5%, respectively). Multivariable analysis revealed age (adjusted odds ratio, 1.05; P < .001), precorrection Haller Index (adjusted odds ratio, 1.10; P < .033), and early-phase institutional experience (adjusted odds ratio, 1.59; P < .002) as independent predisposing risk factors. The optimal age of correction was 12 years, and the compounded complication rate correlated exponentially with age with a doubling time of 7.2 years. Complications increased 2.2-fold when the Haller index increased to 5 or more units. CONCLUSIONS: Minimally invasive repair of pectus excavatum is associated with a high compounded complication rate that increases exponentially with age and high Haller Index. Consequently, we recommend repair during late childhood and early adolescence, and emphasize the importance of informing patients and relatives about the significant risks of adult correction as well as the need of 2 consecutive procedures taking the complication profile into account before planning surgery.

Efficacy of avoiding chest drains after video-assisted thoracoscopic surgery wedge resection: protocol for a randomised controlled trial.

INTRODUCTION: The use of routine postoperative chest drains after video-assisted thoracoscopic surgery (VATS) of the lung is a practice based on tradition with the aim of draining fluid and air. However, new evidence suggests that chest drains can be avoided in selected cases. With this randomised controlled trial, we wish to establish the efficacy and safety of avoiding postoperative chest drains compared with routine postoperative chest drains. METHODS AND ANALYSIS: This is a two-centre randomised controlled trial without allocation concealment, but where randomisation occurs after the end of procedure leaving operative personnel blinded during surgery. The sample size is calculated to show a difference in pain measurements using the Numeric Rating Scale under different circumstances and at different time points to show superiority of the intervention. The trial is pragmatic by design to reflect the daily clinical scenario and with the aim of increasing the external validity of the results. ETHICS AND DISSEMINATION: Approval by the local ethics committees has been obtained for both sites. The study was registered with ClinicalTrials.gov (NCT05358158) prior to inclusion. The results of the trial will be disseminated by publication in an international journal and presentation at major international thoracic surgical meetings. ARTICLE SUMMARY: This is a randomised controlled trial estimating the effects of avoiding a chest drain after VATS wedge resection of the lung on pain, total morphine use, quality of life and complications. TRIAL REGISTRATION NUMBER: NCT05358158.

Risk and Timing of Venous Thromboembolism After Surgery for Lung Cancer: A Nationwide Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable serious complication in patients with lung cancer undergoing thoracic operation. We examined the risk and timing of VTE after surgery for primary non-small cell lung cancer (NSCLC). METHODS: All patients undergoing operation for NSCLC in Denmark between 2003 and 2021 were identified in the Danish Lung Cancer Registry. VTE events in the year after operation were assessed by stage, patient characteristics, and surgical procedure. RESULTS: We identified 13,197 patients who underwent operation for NSCLC in 2003 to 2021 (mean age, 67.6 years; 50% female); 10,524 (79.7%) had stage I-II NSCLC, and 2673 (20.3%) had stage III-IV. During 1-year follow-up, there were 335 VTE events, yielding a rate of 2.87 events/100 person-years and an absolute risk of 3.3% (95% CI, 2.3-4.0). VTE risk increased with advancing cancer stage (1.8% for stage I vs 3.9% for stage IV) but varied little by pathologic type, sex, and comorbidity level. Bilobectomy was associated with highest VTE risk (4.8%; 95% CI, 3.2-6.9), followed by pneumonectomy (3.5%; 95% CI, 2.3-5.0). The hazard of VTE was highest during the first 3 months after operation, after which it declined. For stage IV cancer, hazards increased again after 6 months. At 1 year, all-cause death was 12.6% (95% CI, 12.0%-13.1%). CONCLUSIONS: VTE developed in 3.3% of patients undergoing operation for NSCLC, most commonly within 3 months postoperatively. Prolonged thromboprophylaxis could be considered, particularly in those with advanced cancer stage and undergoing extended resections.

Thrombin Generation Markers as Predictors of Cancer-Associated Venous Thromboembolism: A Systematic Review.

Venous thromboembolism (VTE) is a main contributor to morbidity and mortality in cancer patients. Biomarkers with the potential to predict cancer-associated VTE are continually sought. Of these, markers of thrombin generation present a likely option. The present systematic review examines the ability of three widely used biomarkers of thrombin generation: prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and ex vivo thrombin generation, to predict VTE in both solid and hematologic adult cancer patients. Relevant studies were identified in the PubMed and Embase databases, and the review conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Each study was evaluated using the quality assessment tool from the National Heart, Lung, and Blood Institute. The review protocol was published on PROSPERO with identifier CRD42022362339. In total, 24 papers were included in the review: 11 reporting data on F1.2, 9 on TAT, and 12 on ex vivo thrombin generation. The quality ratings of the included studies varied from good (n = 13), fair (n = 8), to poor (n = 3) with a high heterogenicity. However, F1.2, TAT complex, and ex vivo thrombin generation were all found to be associated with the development of VTE. This association was most pronounced for F1.2. Furthermore, the determination of F1.2 was able to improve the precision of several established risk assessment scores. In conclusion, markers of thrombin generation were found to be elevated in cancer patients with VTE, and particularly, F1.2 was found to be a promising predictor of cancer-associated VTE.

Comparison of video assisted thoracoscopic surgery and thoracotomy for treatment of pleural infection stage II and III: a literature review.

Background and Objective: Pleural infection is associated with significant mortality and morbidity worldwide, with a steadily increasing incidence. We sought to investigate whether video-assisted thoracic surgery (VATS) or thoracotomy provides the best outcomes in the treatment of stage II and III pleural infection as indications remain controversial. Methods: Systematic review of relevant articles from the PubMed database. Key Content and Findings: Nine non-randomized retrospective studies published between 1996 and 2020 with a total of 2,121 patients were included. Results varied between studies, but overall shorter operative and recovery times and greater patient satisfaction were demonstrated using VATS compared with thoracotomy. Conclusions: Although VATS and thoracotomy are viable treatment options for stage II and III pleural infection, VATS has potential advantages in terms of decreased operation time, fewer days with tube drainage, shorter postoperative hospital stay, reduced postoperative pain, increased patient satisfaction with the procedure, and wound appearance. VATS has limitations in the treatment of patients with stage III pleural infection, where delayed surgical referral has been shown to increase the risk of intraoperative conversion to thoracotomy. The data to date implies that debridement by VATS should be proposed as soon as possible in stage II pleural infection and considered in cases of stage III pleural infection.

Safe and efficient 2-step implementation of totally minimally invasive esophagectomy.

Background: The clinical benefits of totally minimal invasive esophagectomy (TIME) compared to open esophagectomy are documented and include reduced morbidity like pulmonary infections, shorter hospital stay and an increase in short-term quality of life. However, transition to TIME can be associated with a learning curve associated increased morbidity. We report our implementation of TIME using a 2-step approach, where the thoracoscopic part was added to the laparoscopic part in carefully selected patients. The hypothesis was that the 2-step implementation provides a safe and efficient implementation without compromising the outcomes for the patients. The aim of this study was to evaluation the implementation of minimal invasive esophagectomy at Aarhus University Hospital, where a 2-step implementation strategy has been used. Methods: In this retrospective observational cohort study a total of 369 patients with esophagus or gastroesophageal cancers underwent esophagectomy from September 1st, 2016 to July 31st, 2021 in a single high-volume tertiary institution. Totally minimally invasive Ivor Lewis esophagectomy was performed by experienced minimal invasive surgeons in 120 of the cases. The study presents the complication rates of the TIME patients in the implementation phase. Results: Anastomotic leakage occurred in 7.5% of the cases and pneumonia occurred in 5.8% of the cases. The lymph node count reached 16 or more in 94.3% of the cases and R0-resection was performed in 98.3% of the cases. Textbook outcome for esophageal cancer surgery was achieved in 45.8% of the patients. Conclusions: Hybrid minimal invasive esophagectomy can serve as a step towards totally minimally invasive esophagectomy. In our institution, major learning curve associated complications was avoided and a high level of cancer control was achieved by a 2-step implementation strategy in carefully selected patients.

Endobronchial valve treatment in chronic obstructive pulmonary disease: A qualitative study of patients' expectations.

Objectives: Endobronchial valve (EBV) treatment is a treatment option for selected patients with severe chronic obstructive pulmonary disease (COPD) to reduce dyspnea and improve quality of life. However, the procedure is associated with risk of complications, and not all patients achieve the expected outcomes. The present study explores patients' expectations while waiting for EBV treatment. Methods: Fifteen patients accepted for EBV treatment at Aarhus University Hospital in Denmark from October 2020 to June 2021 participated in a 30-min, semi-structured interview about (1) the experience of living with COPD and (2) expectations regarding EBV. Results: Four themes were identified: a life of reduced quality; hopes and expectations; information about EBV; and perception of risks. Most patients described their lives as not worth living, and they hoped that EBV would give them their physical and social lives back, while also being aware that EBV would probably not work miracles. Patients' information seeking was influenced by their hopes and expectations to the treatment. They filtered out negative information, focusing on the hope for a positive outcome. This made them willing to run the risk of complications. Conclusion: Living a life of considerably reduced quality, patients might have an increased focus on potential positive effects of EBV treatment while filtering out information about potential side effects. This might bias their decision-making process.

Risk of recurrent cancer-associated venous thromboembolism: A Danish nationwide cohort study.

BACKGROUND: Predictive factors for recurrent cancer-associated venous thromboembolism have been inconsistent across previous studies. To provide data for improved risk stratification, we described the risk of recurrent venous thromboembolism overall and across age, sex, calendar period, cancer type, Ottawa risk score, cancer stage, and cancer treatment in a nationwide cohort of patients with active cancer. METHODS: Using Danish administrative registries, we identified a cohort of all adult patients with active cancer and a first-time diagnosis of venous thromboembolism during 2003-2018. We accounted for the competing risk of death and calculated absolute risks of recurrent venous thromboembolism at six months. RESULTS: The population included 34,072 patients with active cancer and venous thromboembolism. Recurrence risks at six months were higher for patients with genitourinary cancer (6.5%), lung cancer (6.1%), gastrointestinal cancer (5.6%), brain cancer (5.2%), and hematological cancer (5.1%) than for patients with gynecological cancer (4.7%), breast cancer (4.1%), and other cancer types (4.8%). Recurrence risks were similar for men (5.2%) and women (4.9%), with and without chemotherapy (5.1%), across Ottawa risk score group (low: 5.0%; high: 5.1%) and across calendar periods but increased with increasing cancer stage. The overall six-month all-cause mortality risk was 26%, and highest for patients with lung cancer (49%) and lowest among breast cancer patients (4.1%). CONCLUSIONS: Six-month recurrence risk after first-time cancer-associated venous thromboembolism was high and varied by cancer type and patient characteristics. Refining risk stratification for recurrence may improve decision-making regarding treatment duration after cancer-associated thromboembolism.

Does the time to diagnosis and treatment influence outcome in adults with pleural infections.

Objective: To investigate the effect of early diagnosis and intervention in adult patients with complicated parapneumonic pleural effusion or pleural empyema and the impact on outcomes. Methods: A systematic review based on a literature search of the PubMed database was performed. Results: Eleven eligible studies were included; nine observational studies and two randomised controlled trials totalling a study population of 10,717 patients. The studies were conducted from 1992 to 2018, all in Europe and Northern America except one. Results varied between studies, but a trend towards better outcome in patients with shorter duration of symptoms and quicker initiation of treatment was found. We found that duration of symptoms before treatment may affect length of hospital stay, rate of conversion to open surgery, and frequency of complications. Conclusion: We found that an earlier intervention in adults suffering from complicated parapneumonic pleural effusion and pleural empyema may potentially improve the outcome of patients in terms of length of stay, conversion to open surgery, and general complications following treatment, but not regarding mortality. Further studies are required to specify the timing of each intervention, and direct comparison in early management of interventions.

The left upper lobe challenge in video-assisted thoracoscopic surgery-use of a composite score to improve the assessment of simulated lobectomy.

AIM: The aim of this study is to develop a reliable composite score based on simulator metrics to assess competency in virtual reality video-assisted thoracoscopic surgery lobectomy and explore the benefits of combining it with expert rater assessments. METHODS: Standardized objective assessments (time, bleeding, economy of movement) and subjective expert rater assessments from 2 previous studies were combined. A linear mixed model including experience level, lobe and the number of previous simulated procedures was applied for the repeated measurements. Reliability for each of the 4 assessments was calculated using Cronbach's alpha. The Nelder-Mead numerical optimization algorithm was used for optimal weighting of scores. A pass-fail standard for the composite score was determined using the contrasting groups' method. RESULTS: In total, 123 virtual reality video-assisted thoracoscopic surgery lobectomies were included. Across the 4 different assessments, there were significant effects (P < 0.01) of experience, lobe, and simulator experience, but not for simulator attempts on bleeding (P = 0.98). The left upper lobe was significantly more difficult compared to other lobes (P = 0.02). A maximum reliability of 0.92 could be achieved by combining the standardized simulator metrics with standardized expert rater scores. The pass/fail level for the composite score when including 1 expert rater was 0.33. CONCLUSIONS: Combining simulator metrics with 1 or 2 raters increases reliability and can serve as a more objective method for assessing surgical trainees. The composite score may be used to implement a standardized and feasible simulation-based mastery training program in video-assisted thoracoscopic surgery lobectomy.

Assessing VATS competence based on simulated lobectomies of all five lung lobes.

OBJECTIVES: To determine the number of procedures and expert raters necessary to provide a reliable assessment of competence in Video-Assisted Thoracoscopic Surgery (VATS) lobectomy. METHODS: Three randomly selected VATS lobectomies were performed on a virtual reality simulator by participants with varying experience in VATS. Video recordings of the procedures were independently rated by three blinded VATS experts using a modified VATS lobectomy assessment tool (VATSAT). The unitary framework of validity was used to describe validity evidence, and generalizability theory was used to explore the reliability of different assessment options. RESULTS: Forty-one participants (22 novices, 10 intermediates, and 9 experienced) performed a total of 123 lobectomies. Internal consistency reliability, inter-rater reliability, and test-retest reliability were 0.94, 0.85, and 0.90, respectively. Generalizability theory found that a minimum of two procedures and four raters or three procedures and three raters were needed to ensure the overall reliability of 0.8. ANOVA showed significant differences in test scores between the three groups (P < 0.001). A pass/fail level of 19 out of 25 points was established using the contrasting groups' standard setting method, leaving one false positive (one novice passed) and zero false negatives (all experienced passed). CONCLUSION: We demonstrated validity evidence for a VR simulator test with different lung lobes, and a credible pass/fail level was identified. Our results can be used to implement a standardized mastery learning training program for trainees in VATS lobectomies that ensures that everyone reaches basic competency before performing supervised operations on patients.

Intrapleural fibrinolysis and DNase versus video-assisted thoracic surgery (VATS) for the treatment of pleural empyema (FIVERVATS): protocol for a randomised, controlled trial - surgery as first-line treatment.

INTRODUCTION: Pleural empyema is a frequent disease with a high morbidity and mortality. Current standard treatment includes antibiotics and thoracic ultrasound (TUS)-guided pigtail drainage. Simultaneously with drainage, an intrapleural fibrinolyticum can be given. A potential better alternative is surgery in terms of video-assisted thoracoscopic surgery (VATS) as first-line treatment. The aim of this study is to determine the difference in outcome in patients diagnosed with complex parapneumonic effusion (stage II) and pleural empyema (stage III) who are treated with either VATS surgery or TUS-guided drainage and intrapleural therapy (fibrinolytic (Alteplase) with DNase (Pulmozyme)) as first-line treatment. METHODS AND ANALYSIS: A national, multicentre randomised, controlled study. Totally, 184 patients with a newly diagnosed community acquired complicated parapneumonic effusion or pleural empyema are randomised to either (1) VATS procedure with drainage or (2) TUS-guided pigtail catheter placement and intrapleural therapy with Actilyse and DNase. The total follow-up period is 12 months. The primary endpoint is length of hospital stay and secondary endpoints include for example, mortality, need for additional interventions, consumption of analgesia and quality of life. ETHICS AND DISSEMINATION: All patients provide informed consent before randomisation. The research project is carried out in accordance with the Helsinki II Declaration, European regulations and Good Clinical Practice Guidelines. The Scientific Ethics Committees for Denmark and the Danish Data Protection Agency have provided permission. Information about the subjects is protected under the Personal Data Processing Act and the Health Act. The trial is registered at www. CLINICALTRIALS: gov, and monitored by the regional Good clinical practice monitoring unit. The results of this study will be published in peer-reviewed journals and presented at various national and international conferences. TRIAL REGISTRATION NUMBER: NCT04095676.

Warfarin monitoring and interference by lupus anticoagulant in patients with antiphospholipid syndrome.

INTRODUCTION: Patients with antiphospholipid syndrome (APS) receive vitamin K antagonists, which warrants international normalized ratio (INR) monitoring. Research has indicated that presence of lupus anticoagulant (LA) can interfere with INR results obtained by point-of-care testing (POCT) devices. We aimed to investigate whether a systematic difference exists between POCT-INR and plasma-INR in patients with APS. MATERIALS AND METHODS: We compared 291 paired POCT- and plasma-INR results from 52 LA-positive APS patients receiving warfarin with each patient having a minimum of three paired measurements of paired POCT-INR (CoaguChek, Roche Diagnostics) and plasma-INR. Agreement limits were considered satisfactory if differences were within ±0.4 INR for plasma-INR < 2.0, within ±20% for plasma-INR 2.0 to 3.5, within ±20% for plasma-INR > 3.5 to 4.5, within ±25% for plasma-INR > 4.5 to 6.0 and within ±30% for plasma-INR > 6.0. RESULTS: A strong positive correlation was found between POCT- and plasma-INR, Spearman's rho (95% CI) = 0.72 (0.65-0.78), p < 0.001. The average bias was 0.1 INR (3.7%), p < 0.001. 79% of paired INR results met the agreement limits with 67% of the diverging POCT-INRs being from a subset of five patients, who had consistently higher POCT- than plasma-INR. CONCLUSIONS: The majority of LA-positive APS patients had no clinically significant difference between POCT-INR and plasma-INR. However, in a subset of patients, clinically significant systematic differences were found. Consequently, systematic comparison of a minimum three paired POCT- and plasma-INR results is recommended before implementing POCT-INR monitoring in LA-positive APS patients.

Localized malignant mesothelioma in the stomach and mediastinum.

Localized malignant mesothelioma is rare. It has a histological pattern identical to diffuse malignant mesothelioma but without diffuse serosal spread. Localized malignant mesothelioma typically originates from the pleura, peritoneum or pericardium, but can occasionally develop from organs. Our cases represent what might be the largest mediastinal localized malignant mesothelioma described and the first presentation of the epithelioid type in the stomach of an adult.