Multicentre retrospective analysis on pulmonary metastasectomy: an European perspective.

OBJECTIVES: To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS: Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS: A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25-75% = 1-2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS: Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice.

The role of the surgical volume for clinical outcomes in VATS lobectomy for lung cancer: a national large database multicenter analysis.

Improving the quality of lung cancer care at a cost that can be sustained is a hotly debated issue. High-risk, low-volume procedures (such as lung resections) are believed to improve significantly when centralised in high-volume centres. However, limited evidence exists to support volume requirements in lung cancer surgery. On the other hand, there was no evidence that the number of lung resections affected either the short-term perioperative results or the long-term cost. Using data from an extensive nationwide registry, this study investigated the correlations between surgical volumes and selected perioperative outcomes. A retrospective analysis of a prospectively filled national registry that follows stringent quality assurance and security procedures was conducted to ensure data accuracy and security. Patients who underwent VATS lobectomy from 2014 to 2019 at the participating centres were included. Selected perioperative outcomes were reported. Total direct hospital cost is measured at discharge for hospitalisations with a primary diagnosis of lung cancer, hospital stay costs, and postoperative length of hospital stay after lobectomy. After the propensity score matched, centres were divided into three groups according to the surgical volume of the unit where VATS lobectomies were performed (high-volume centre: > 500 lobectomies; medium-volume centre: 200-500 lobectomies; low-volume centre: < 200 lobectomies). 11,347 patients were included and matched (low-volume center = 2890; medium-volume center = 3147; high-volume center = 2907). The mean operative time density plot (Fig. 1A) showed no statistically significant difference (p = 0.67). In contrast, the density plot of the harvested lymph nodes (Fig. 1B) showed significantly higher values in the high-volume centres (p = 0.045), albeit without being clinically significant. The adjusted rates of any and significant complications were higher in the low-volume centre (p = 0.034) without significantly affecting the length of hospital stay (p = 0.57). VATS lobectomies for lung cancer in higher-volume centres seem associated with a statistically significantly higher number of harvested lymph nodes and lower perioperative complications, yet without any significant impact in terms of costs and resource consumption. These findings may advise the investigation of the learning curve effect in a complete economic evaluation of VATS lobectomy in lung cancer. Fig. 1 The mean operative time density plot showed no statistically significant difference (p = 0.67).

An evaluation of the methodological quality of published guidelines for the surgical treatment of pleural mesothelioma.

BACKGROUND: To benchmark their quality, a project was designed to analyze the methodology of previous guidelines and recommendations for malignant pleural mesothelioma projects. METHODS: A narrative literature search was conducted, and each guideline was evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and rated on a seven-point scale for its many items and domains. RESULTS: Six guidelines that met the inclusion requirements were evaluated. Due to greater development rigor and editorial independence, the engagement of scientific societies was associated with an improvement in methodological quality. CONCLUSION: According to the standards of AGREE II, the methodological quality of earlier guidelines was relatively low. Nonetheless, two previously published guidelines could serve as a template for the establishment of the most effective methodological quality guidelines.

Artificial Neural Networks in Lung Cancer Research: A Narrative Review.

BACKGROUND: Artificial neural networks are statistical methods that mimic complex neural connections, simulating the learning dynamics of the human brain. They play a fundamental role in clinical decision-making, although their success depends on good integration with clinical protocols. When applied to lung cancer research, artificial neural networks do not aim to be biologically realistic, but rather to provide efficient models for nonlinear regression or classification. METHODS: We conducted a comprehensive search of EMBASE (via Ovid), MEDLINE (via PubMed), Cochrane CENTRAL, and Google Scholar from April 2018 to December 2022, using a combination of keywords and related terms for "artificial neural network", "lung cancer", "non-small cell lung cancer", "diagnosis", and "treatment". RESULTS: Artificial neural networks have shown excellent aptitude in learning the relationships between the input/output mapping from a given dataset, without any prior information or assumptions about the statistical distribution of the data. They can simultaneously process numerous variables, managing complexity; hence, they have found broad application in tasks requiring attention. CONCLUSIONS: Lung cancer is the most common and lethal form of tumor, with limited diagnostic and treatment methods. The advances in tailored medicine have led to the development of novel tools for diagnosis and treatment. Artificial neural networks can provide valuable support for both basic research and clinical decision-making. Therefore, tight cooperation among surgeons, oncologists, and biostatisticians appears mandatory.

The Impact of Surgical Experience in VATS Lobectomy on Conversion and Patient Quality of Life: Results from a Comprehensive National Video-Assisted Thoracic Surgical Database.

OBJECTIVES: Although unexpected conversion during Video-Assisted Thoracic Surgery (VATS) lobectomy is up to 23%, the effects on postoperative outcomes remain debatable. This retrospective study aimed: (i) to identify potential preoperative risk factors of VATS conversion to standard thoracotomy; (ii) to assess the impact of surgical experience in VATS lobectomy on conversion rate and patient health-related quality of life. METHODS: We extracted detailed information on VATS lobectomy procedures performed consecutively (2014-2019). Predictors of conversion were assessed with univariable and multivariable logistic regressions. To assess the impact of VATS lobectomy experience, observations were divided according to surgeons' experiences with VATS lobectomy. The impact of VATS lobectomy experience on conversion and occurrence of postoperative complications was evaluated using logistic regressions. The impact of VATS lobectomy experience on EuroQoL-5D (EQ-5D) scores at discharge was assessed using Tobit regressions. RESULTS: A total of 11,772 patients underwent planned VATS for non-small-cell lung cancer (NSCLC), with 1074 (9.1%) requiring conversion to thoracotomy. The independent predictors at multivariable analysis were: FEV1% (OR = 0.99; 95% CI: 0.98-0.99, p = 0.007), clinical nodal involvement (OR = 1.43; 95% CI: 1.08-1.90, p = 0.014). Experienced surgeons performed 4079 (34.7%) interventions. Experience in VATS lobectomy did not show a relevant impact on the risk of open surgery conversion (p = 0.13) and postoperative complications (p = 0.10), whereas it showed a significant positive impact (p = 0.012) on EQ-5D scores at discharge. CONCLUSIONS: Clinical nodal involvement was confirmed as the most critical predictor of conversion. Greater experience in VATS lobectomy did not decrease conversion rate and postoperative complications but was positively associated with postoperative patient quality of life.

Minimally Invasive Anatomical Segmentectomy versus Lobectomy in Stage IA Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: A systematic review and meta-analysis was performed to assess potential differences in perioperative outcomes and disease-free survival (DFS) and overall survival (OS) of patients with pathological stage IA non-small cell lung cancer (NSCLC) who underwent minimally invasive anatomical segmentectomy or lobectomy. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of EMBASE (through Ovid), MEDLINE (via PubMed), and Cochrane CENTRAL was conducted. Two researchers independently reviewed each eligible study that included patients with stage IA NSCLC who underwent minimally invasive anatomical segmentectomy and lobectomy and compared perioperative and/or survival outcomes of patients. RESULTS: A total of 887 publications were identified. Of these, 10 articles met our eligibility criteria. A significantly higher number of lymph nodes were harvested in lobectomies. The two groups did not significantly differ in postoperative complication rates, DFS, and OS. Patients who underwent segmentectomy had shorter postoperative hospital stays. CONCLUSIONS: Minimally invasive lobectomy and segmentectomy showed comparable short-term and long-term outcomes in stage IA NSCLC patients. Postoperative complication rates were similar. Minimally invasive lobectomies are associated with a higher number of harvested lymph nodes, although this did not affect the final staging or the survival outcomes.

Cover always the bronchial stump! A flap could prevent catastrophic complications even in complete broncho-pleural fistula.

Broncho-pleural fistula after pneumonectomy is a life-threatening condition with very high mortality rate, even if detected early. All symptomatic patients should be treated immediately. The diagnosis in the absence of symptoms poses the real difficulties of management. Early detection of asymptomatic post-pneumonectomy broncho-pleural fistula is usually fortuitous. The use of bronchoscopy allows direct and accurate evaluation of the stump. This reported case allows us to make several considerations on the treatment of fistulas, but above all to consider that the systematic bronchial stump coverage is fundamental not only for preventing fistulas, but also for limiting their enlargement and communication with the residual cavity, in order to prevent catastrophic complications.

Correction to: Cover always the bronchial stump! A flap could prevent catastrophic complications even in complete broncho­pleural fistula.

[This corrects the article DOI: 10.1007/s12055-022-01386-3.].

Immersive Three-dimensional Computed Tomography to Plan Chest Wall Resection for Lung Cancer.

PURPOSE: Chest wall resections for lung cancer treatment remain difficult to plan using standard 2-dimensional computed tomography. Although virtual reality headsets have been used in many medical contexts, they have not been used in chest wall resection planning. DESCRIPTION: We compared preoperative planning of a chest wall surgical resection for lung cancer treatment between senior and resident surgeons who used an immersive virtual reality device and a 2-dimensional computed tomography. EVALUATION: Chest wall resection planning was more accurate when surgeons used virtual reality vs computed tomography analysis (28.6% vs 18.3%, P = .018), and this was particularly true in the resident surgeon group (27.4% vs 8.3%, P = .0025). Predictions regarding the need for chest wall substitutes were also more accurate when they were made using virtual reality vs computed tomography analysis in all groups (96% vs 68.5%, P < .0001). Other studied parameters were not affected by the use of the virtual reality tool. CONCLUSIONS: Virtual reality may offer enhanced accuracy for chest wall resection and reconstruction planning for lung cancer treatment.

Impact of the extent of lung resection on postoperative outcomes of pulmonary metastasectomy for colorectal cancer metastases: an exploratory systematic review.

Background: Pulmonary metastasectomy (PM) with curative intent has become a widely accepted treatment for lung metastases from solid tumours in selected patients, with low perioperative morbidity and mortality. In particular, PM is strongly recommended in selected patients with secondary lesions from colorectal cancer (CRC), due to its excellent postoperative prognosis. Nevertheless, the impact of the extent of PM on recurrence and survival remains controversial. This review aimed at assessing differences in short- and long-term postoperative outcomes depending on the extent of lung resection for lung metastases. Methods: A systematic literature review of studies comparing anatomical and non-anatomical resections of lung metastases was performed (Prospective Register of Systematic Reviews Registration: 254931). A literature search for articles published in English between the date of database inception and January 31, 2021 was performed in EMBASE (via Ovid), MEDLINE (via PubMed) and Cochrane CENTRAL. Retrospective studies, randomised and non-randomised controlled trials were included. The Cochrane Collaboration tool was used to determine the risk of bias for the primary outcome for included studies. Results: Out of 432 papers, three retrospective non-randomised studies (1,342 patients) were selected for systematic reviewing. Although our search design did not exclude any primary tumour histology, all selected studies investigated surgical resection of lung metastases from CRC. Because of variations in the compared surgical approaches to pulmonary metastases, a meta-analysis proved unfeasible. There was a tendency to perform anatomical resections for larger metastases. Multivariate analyses revealed that anatomical resections were protective for recurrence-free survival (RFS), while the impact of such procedures on overall survival (OS) remained uncertain. A significantly higher incidence of resection-margin recurrences was observed in patients who underwent non-anatomical resections. Discussion: Anatomical resections of lung metastases from CRC seem to be associated with improved RFS. However, well-constructed comparative clinical trials focusing on the extent of PM are needed.

Long-term clinical outcomes and prognostic factors of upfront surgery as a first-line therapy in biopsy-proven clinical N2 non-small cell lung cancer.

Background: Multimodality therapy offers the best opportunity to improve pathological N2 non-small cell lung cancer (NSCLC) prognosis. This paper aimed to evaluate the long-term clinical outcomes and the prognostic factors of upfront surgery as first-line therapy in biopsy-proven clinical N2. Methods: Retrospective review of biopsy-proven cN2 NSCLC patients operated between 2007 and 2017. Upfront surgery was considered if the primary tumour was deemed completely resectable, with mediastinal nodal involvement confined to a single station and no preoperative evidence of extranodal tumour invasion. Results: Two hundred eighty-five patients who underwent radical resections were included. One hundred fifty-nine patients (55.8%) received induction chemotherapy. At follow-up completion, 127 (44.6%) patients had died. For the induction chemotherapy group, the median overall survival (OS) was 49 months [95% confidence interval (CI): 38-70 months], and the 5-year OS was 44.4%. The median and 5-year OS for the up front surgery group was 66 months (95% CI: 40-119 months) and 66.3%, respectively. There were no statistically significant differences between treatment approaches (p = 0.48). One hundred thirty-four patients (47.0%) developed recurrence. The recurrence-free survival (RFS) at 5 years was 17% (95% CI: 11-25%) for induction chemotherapy and 22% (95% CI: 9-32%) for upfront surgery; there were no statistically significant differences between groups (p = 0.93). No significant differences were observed based on the clinical N status (OS, p = 0.36; RFS, p = 0.65). Conclusions: Upfront surgery as first-line therapy for biopsy-proven cN2 NSCLC showed favourable clinical outcomes, similar to those obtained after induction chemotherapy followed by surgery. Therefore, it should be considered one of the multimodality treatment options in resectable N2 NSCLC.

Pneumonectomy and broncho-pleural fistula: predicting factors and stratification of the risk.

The goal of the study is to evaluate the different risk factors and stratify the patients, before the surgery, into distinct risk classes. We retrospectively reviewed pre, peri, and postoperative outcomes of 366 consecutive patients who underwent pneumonectomy for lung cancer between the last 10 years (2009-2019). We classified the patients into four classes, depending on preoperative assessments. Differences between groups were assessed with the log-rank test. Multivariable Cox proportional hazards regression analysis was used to assess the independent prognostic significance of the variables associated with the development of BPF at univariate analysis. Finally, we performed non-linear [artificial neural network (ANN)] multiple regression analyses. All tests were two-sided, and p values < 0.05 were considered significant. Fifty-one patients (13.9%) out of 366 developed BPF. Male sex (p = 0.048), right side (p = 0.015), postoperative pulmonary complications (p = 0.0139) and adjuvant treatments (p = 0.0169) were the independent predicting factors of fistulas in multivariate analysis. The right side (p = 0.043) and adjuvant treatments (p = 0.032) were the independent predicting factors of BPF after the ANN analysis. Based on multivariate and artificial neural network analysis and our experience, we observed a trend of growing risk of BPF in the first 4 weeks (early fistula), considering the four classes. Preoperative differentiation of the patients into four risk classes could allow a correct stratification of the growing risk of developing early BPF. This information could be significant to share with patients and the other physicians during the decision-making process, to minimise the risk of BPF.

A Focused Review on Primary Graft Dysfunction after Clinical Lung Transplantation: A Multilevel Syndrome.

Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation (LTx). However, PGD is an umbrella term that encompasses the ongoing pathophysiological and -biological mechanisms occurring in the lung grafts. Therefore, we aim to provide a focused review on the clinical, physiological, radiological, histological and cellular level of PGD. PGD is graded based on hypoxemia and chest X-ray (CXR) infiltrates. High-grade PGD is associated with inferior outcome after LTx. Lung edema is the main characteristic of PGD and alters pulmonary compliance, gas exchange and circulation. A conventional CXR provides a rough estimate of lung edema, while a chest computed tomography (CT) results in a more in-depth analysis. Macroscopically, interstitial and alveolar edema can be distinguished below the visceral lung surface. On the histological level, PGD correlates to a pattern of diffuse alveolar damage (DAD). At the cellular level, ischemia-reperfusion injury (IRI) is the main trigger for the disruption of the endothelial-epithelial alveolar barrier and inflammatory cascade. The multilevel approach integrating all PGD-related aspects results in a better understanding of acute lung failure after LTx, providing novel insights for future therapies.

The Weekday Effect on Morbidity of Lung Cancer Surgery: A Real-World Analysis.

BACKGROUND: Many authors have investigated the possible adverse effects among patients who underwent elective surgery on Friday when compared with patients operated earlier in the week. Nonetheless, the weekday effect is still a matter of debate. This study aimed at investigating the postoperative morbidity rates after lung cancer surgery and their relationship with the weekday the surgery took place. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of patients who underwent elective thoracotomic lobectomies for lung cancer. Categorical data were analyzed using the chi-square test or Fisher's exact test. Association between predictors and binary outcomes while considering the weekday stratification was determined with Cochran-Mantel-Haenszel statistics. To characterize the typical Friday patient, a multiple logistic regression analysis was performed. RESULTS: A total of 817 patients (2015-2019) were identified. Complication rates divided by day of surgery were 164 (20.07%) for patients operated on Mondays, 182 (22.27%) on Tuesdays, 205 (25.09%) on Wednesdays, 172 (21.05%) on Thursdays, and 94 (11.51%) on Fridays. Crude morbidity rates by weekday were Monday 21.53%, Tuesday 20.51%, Wednesday 27.70%, Thursday 20.0%, and Friday 10.26%. No overall association between day of surgery and overall morbidity was found (ρ = 0.095). Median hospital length of stay was 5 days (range: 2-45 days), and there were no statistically significant differences between days. The Cochran-Mantel-Haenszel statistics showed no association between morbidity and the weekday. CONCLUSION: In patients undergoing elective lobectomies for lung cancer, the weekday of surgery was not statistically significantly associated with an increase in the risk of postoperative morbidity.

Preserving the eponym: Klinkenbergh technique for bronchial stump suturing.

The technique for bronchial stump suturing following lung resection which is currently applied in the Department of Thoracic Surgery at the University Hospitals Leuven, Belgium owes its name to the Dutch surgeon Dr. Klinkenbergh (1891-1985). A true pioneer of cardiothoracic surgery in Europe, Dr. Klinkenbergh dedicated himself to the surgical treatment of pulmonary tuberculosis. His work was praised by his peers for his precision and the reasoning behind every gesture. The Klinkenbergh technique consists in performing two running sutures which cross each other 'in the same manner as the laces of a shoe' to close the bronchus, limiting the occurrence of broncho-pleural fistulas. In our experience with more than 100 patients in the last 5 years (2016-2020) who underwent open pneumonectomy for benign or malignant disease, less than 2% developed post-operative broncho-pleural fistulas.

Urinary Biomarkers for Early Diagnosis of Lung Cancer.

Lung cancer is the leading cause of cancer deaths worldwide. Its early detection has the potential to significantly impact the burden of the disease. The screening and diagnostic techniques in current use suffer from limited specificity. The need therefore arises for a reliable biomarker to identify the disease earlier, which can be integrated into a test. This test would also allow for the recurrence risk after surgery to be stratified. In this context, urine could represent a non-invasive alternative matrix, with the urinary metabolomic profile offering a potential source for the discovery of diagnostic biomarkers. This paper aims to examine the current state of research and the potential for translation into clinical practice.

Chest wall resection and reconstruction for primary and metastatic sarcomas: an 11-year retrospective cohort study.

OBJECTIVES: Chest wall sarcomas are rare, aggressive malignancies, the management of which mainly revolves around surgery. Radical tumour excision with free margins represents the optimal treatment for loco-regional clinically resectable disease. The objective of this study was to review our 11-year experience with chest wall resection for primary and metastatic sarcomas, focusing on surgical techniques and strategies for reconstruction. METHODS: Retrospective analysis of a comprehensive database of patients who underwent chest wall resection for primary or secondary sarcoma at our Institute from January 2009 to December 2019. RESULTS: Out of 26 patients, 21 (81%) suffered from primary chest wall sarcoma, while 5 (19%) had recurring disease. The median number of resected ribs was 3. Sternal resection was performed in 6 cases (23%). Prosthetic thoracic reconstruction was deemed necessary in 24 cases (92%). Tumour recurrence was observed in 15 patients (58%). The median overall survival was 73.6 months. Primary and secondary tumours showed comparable survival (P = 0.49). At univariate analysis, disease recurrence and infiltrated margins on pathological specimens were associated with poorer survival (P = 0.014 and 0.022, respectively). In patients with primary sarcoma, the median progression-free survival was 13.3 months. Associated visceral resections were significantly associated to postoperative complications (P = 0.02). CONCLUSIONS: Chest wall resection followed by prosthetic reconstruction is feasible in carefully selected patients and should be performed by experienced surgeons with the aim of achieving free resection margins, resulting in improved long-term outcomes.

Prognostic Value of the Hemoglobin/Red Cell Distribution Width Ratio in Resected Lung Adenocarcinoma.

BACKGROUND: The ratio of hemoglobin to red cell distribution width (HRR) has been described as an effective prognostic factor in several types of cancer. The aim of this study was to investigate the prognostic role of preoperative HRR in resected-lung-adenocarcinoma patients. METHODS: We enrolled 342 consecutive patients. Age, sex, surgical resection, adjuvant treatments, pathological stage, preoperative hemoglobin, red cell distribution width, and their ratio were recorded for each patient. RESULTS: Mean age was 66 years (SD: 9.0). There were 163 females (47.1%); 169 patients (49.4%) had tumors at stage I, 71 (20.8%) at stage II, and 102 (29.8%) at stage III. In total, 318 patients (93.0%) underwent lobectomy, and 24 (7.0%) pneumonectomy. Disease-free survival multivariable analysis disclosed an increased hazard ratio (HR) of relapse for preoperative HRR lower than 1.01 (HR = 2.20, 95%CI: (1.30-3.72), p = 0.004), as well as for N1 single-node (HR = 2.55, 95%CI: (1.33-4.90), p = 0.005) and multiple-level lymph node involvement compared to N0 for both N1 (HR = 9.16, 95%CI:(3.65-23.0), p < 0.001) and N2 (HR = 10.5, 95%CI:(3.44-32.2, p < 0.001). CONCLUSION: Pre-operative HRR is an effective prognostic factor of disease-free survival in resected-lung-adenocarcinoma patients, together with the level of pathologic node involvement.