Long-Term Survival Analysis of Pleural Mesothelioma Patients Undergoing Surgery: Brief Report From a Tertiary Referral Centre.

OBJECTIVES: to date, no consensus has been reached on the surgical gold-standard in pleural mesothelioma (PM). We retrospectively reviewed our experience as a tertiary referral centre, to compare short- and long-term survival of PM patients undergoing different types of surgery. METHODS: in retrospective, observational, single-centre study, we analysed all the patients histologically diagnosed with PM undergoing surgical procedures with palliative or curative intent at IRCCS Istituto Nazionale dei Tumori of Milan, Italy, from January 2003 to December 2020. The primary study endpoint was 10-year overall survival (OS) in three different types of resections: extra-pleural-pneumonectomy (EPP), pleurectomy/decortication (P/D), partial-pleurectomy/pleural-biopsy (PP/B). Secondary endpoints were postoperative hospital stay and postoperative 30-day and 90-day mortality rates. The survival function was estimated using Kaplan-Meier, and the Log-rank test was used for testing differences. Univariable and Multivariable Cox regression models were implemented to estimate Hazard Ratio (HR) for all variables of interest. RESULTS: 243 consecutive patients were enrolled, EPP was performed in 49 (20.2%), P/D in 58 (23.8%), PP/B in 136 (56.0%) patients. The median follow-up time was 19.8 months. 10-year OS was significantly better for P/D group (16%, Log-Rank test p<0.0001) compared to PP/B (1.8%) and EPP (0%). No statistically significant differences were found among the 3 surgical groups in 30- and 90-day mortality rates. At multivariable analysis, gender (male, HR=1.58), type of resection (P/D, HR=0.55) and surgery date (recent years, HR=0.61) were found to be independent prognostic factors for OS. CONCLUSIONS: in PM, lung-sparing curative approach (e.g. P/D) should be preferred in highly selected patients and in highly experienced centres, whenever appropriate. Anyway, when P/D is not indicated, adopting palliative/conservative management (e.g. PP/B) could ensure comparable results as extremely aggressive surgeries (e.g. EPP). The aim of surgery in PM should not be reaching complete resection, but rather accomplishing significant resection allowing to complete the multimodality treatment in highly selected patients in experienced centers.

Comparison between the Airgo™ Device and a Metabolic Cart during Rest and Exercise.

The aim of this study is to compare the accuracy of Airgo™, a non-invasive wearable device that records breath, with respect to a gold standard. In 21 healthy subjects (10 males, 11 females), four parameters were recorded for four min at rest and in different positions simultaneously by Airgo™ and SensorMedics 2900 metabolic cart. Then, a cardio-pulmonary exercise test was performed using the Erg 800S cycle ergometer in order to test Airgo™'s accuracy during physical effort. The results reveal that the relative error median percentage of respiratory rate was of 0% for all positions at rest and for different exercise intensities, with interquartile ranges between 3.5 (standing position) and 22.4 (low-intensity exercise) breaths per minute. During exercise, normalized amplitude and ventilation relative error medians highlighted the presence of an error proportional to the volume to be estimated. For increasing intensity levels of exercise, Airgo™'s estimate tended to underestimate the values of the gold standard instrument. In conclusion, the Airgo™ device provides good accuracy and precision in the estimate of respiratory rate (especially at rest), an acceptable estimate of tidal volume and minute ventilation at rest and an underestimation for increasing volumes.

Is central lung tumour location really predictive for occult mediastinal nodal disease in (suspected) non-small-cell lung cancer staged cN0 on 18F-fluorodeoxyglucose positron emission tomography-computed tomography?

OBJECTIVES: Current guidelines recommend preoperative invasive mediastinal staging in centrally located tumours with negative mediastinum on positron emission tomography-computed tomography, based on a 20-30% prevalence of occult mediastinal disease (pN2-3). However, a uniform definition of central tumour location is lacking. Our objective was to determine the best definition in predicting occult pN2-3. METHODS: A single-institution database was queried for patients with (suspected) non-small-cell lung cancer staged cN0 after positron emission tomography-computed tomography and referred to invasive staging and/or primary surgery. We evaluated 5 definitions: inner 1/3, inner 2/3, contact with bronchovascular structures, ≤2 cm from bronchus or endobronchial visualization. RESULTS: Between 2005 and 2015, 813 patients were eligible (cT1: 42%, cT2: 28%, cT3: 17% and cT4: 11%). Invasive mediastinal staging and resection were performed in 30% and 97% of patients, respectively. Any nodal upstaging (pN+) was found in 21% of patients, of whom pN2-3 was found in 8%. Central tumour location demonstrated 4 times higher odds for any pN+ [for inner 1/3 vs outer 2/3, odds ratio 3.90 (95% confidence interval 2.24-6.77), P < 0.001], whereas no significantly different odds was observed for pN2-3. The discriminative ability for pN+ was not significantly different between the several definitions. CONCLUSIONS: The prevalence of occult pN2-3 was only 8% when modern fusion positron emission tomography-computed tomography imaging pointed at clinical N0 non-small-cell lung cancer. None of the 5 verified definitions of centrality was predictive for occult pN2-3. However, each definition of centrality was related to any pN+ at a prevalence of 21%, without significant differences in discriminative ability between definitions. These data question whether indication for preoperative invasive mediastinal staging should be based on centrality alone.

Tailored intraoperative localization of non-palpable pulmonary lesions for thoracoscopic wedge resection using hybrid room technology.

INTRODUCTION: VATS wedge resection can require conversion to thoracotomy when pulmonary lesions cannot be identified. Hybrid operating rooms (HORs) provide real-time image acquisition capabilities allowing the intraoperative placement of markers to facilitate the removal of non-palpable nodules during VATS. OBJECTIVES: To present our workflow based on the alternative use of two different markers according to the location of the lung lesion and report our initial results. METHODS: All consecutive patients with non-palpable lesions requiring VATS wedge resection underwent localization of the targets in HOR. Lesions were considered non-palpable if they were small (<1 cm), deep (>1 cm from surface), subsolid, or located within a dystrophic area. Anesthetized patients were placed in lateral decubitus. Cone-beam CT (CBCT) was performed, and the needle trajectory was planned using Syngo iGuide Needle Guidance. Metal hook-wire or coil was placed, according to our workflow, close to the lesion and their position was verified by CBCT or fluoroscopy. RESULTS: Eleven VATS wedge resections were performed in 10 patients with 12 non-palpable lesions. The localization was performed with seven hook-wires and four coils in 30 minutes (range 17-56 minutes). The median estimated total effective dose was 11.6 mSv (range 1.9-24.7 mSv). Eleven lesions were removed by VATS, and one deep nodule required a thoracotomy. No complications were observed. CONCLUSIONS: Our experience confirms that HOR is suitable for simultaneous localization and VATS resection of 'difficult' pulmonary lesions. A versatile approach, using different devices, seems advisable for the removal of targets in every clinical scenario, reducing the VATS conversion rate.

Multicentric evaluation of the impact of central tumour location when comparing rates of N1 upstaging in patients undergoing video-assisted and open surgery for clinical Stage I non-small-cell lung cancer†.

OBJECTIVES: Large retrospective series have indicated lower rates of cN0 to pN1 nodal upstaging after video-assisted thoracic surgery (VATS) compared with open resections for Stage I non-small-cell lung cancer (NSCLC). The objective of our multicentre study was to investigate whether the presumed lower rate of N1 upstaging after VATS disappears after correction for central tumour location in a multivariable analysis. METHODS: Consecutive patients operated for PET-CT based clinical Stage I NSCLC were selected from prospectively managed surgical databases in 11 European centres. Central tumour location was defined as contact with bronchovascular structures on computer tomography and/or visibility on standard bronchoscopy. RESULTS: Eight hundred and ninety-five patients underwent pulmonary resection by VATS (n = 699, 9% conversions) or an open technique (n = 196) in 2014. Incidence of nodal pN1 and pN2 upstaging was 8% and 7% after VATS and 15% and 6% after open surgery, respectively. pN1 was found in 27% of patients with central tumours. Less central tumours were operated on by VATS compared with the open technique (12% vs 28%, P < 0.001). Logistic regression analysis showed that only tumour location had a significant impact on N1 upstaging (OR 6.2, confidence interval 3.6-10.8; P < 0.001) and that the effect of surgical technique (VATS versus open surgery) was no longer significant when accounting for tumour location. CONCLUSIONS: A quarter of patients with central clinical Stage I NSCLC was upstaged to pN1 at resection. Central tumour location was the only independent factor associated with N1 upstaging, undermining the evidence for lower N1 upstaging after VATS resections. Studies investigating N1 upstaging after VATS compared with open surgery should be interpreted with caution due to possible selection bias, i.e. relatively more central tumours in the open group with a higher chance of N1 upstaging.

Lobar lung transplantation from deceased donors: A systematic review.

AIM: To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio. METHODS: We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx. RESULTS: Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx (n = 138) was associated with a lower one-year-survival compared to conventional-LTx (n = 539) (65.1% vs 84.1%, P < 0.001). CONCLUSION: Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option.

Central tumour location should be considered when comparing N1 upstaging between thoracoscopic and open surgery for clinical stage I non-small-cell lung cancer.

OBJECTIVES: Nodal upstaging is a quality indicator for oncological thoracic surgery and is found in up to 25% of patients with clinical stage I (cStage-I) non-small-cell lung cancer (NSCLC). In large retrospective series, lower N1 upstaging was reported after video-assisted thoracic surgery (VATS) resections. We studied the impact of central primary tumour location on nodal upstaging in cStage-I NSCLC. METHODS: Consecutive patients operated for cStage-I NSCLC were selected from a prospectively managed surgical database. Tumour location was classified as central if the lesion was visible during standard video bronchoscopy. A nodal station mapping was drawn for each patient based on final pathological examination. Univariable and additive multivariable binary logistic regression analyses were performed. RESULTS: Between 2007-2014, 334 patients underwent anatomical resection for cStage-I NSCLC, either by open thoracotomy (n = 158) or by VATS (n = 176; conversion rate 1.7%). All patients underwent imaging with [(18)F]-fluorodeoxyglucose positron emission tomography and computer tomography. Invasive mediastinal staging was performed in 24.6% of patients. There were more central tumours in the open group (24.1%, n = 38) compared with the VATS group (4.5%, n = 8). There was no significant difference between the number (mean ± standard deviation) of nodal stations examined (open 5 ± 1.9 vs VATS 5 ± 1.7, P = 0.99). Pathological nodal upstaging was found in 15.9% (n = 53) of cStage-I patients. Nodal pN1 and pN2 upstaging were 13.3 and 8.2%, respectively, for the open group, and 6.3 and 4.5%, respectively, for the VATS group. In 32.6% (n = 15/46) of patients with a central cStage-I tumour pN1, upstaging was found. A binary logistic regression model (including tumour location, technique, tumour size, gender and histology) showed that only tumour location had a significant impact on pN1 upstaging [peripheral versus central; odds ratio (OR) 5.07 (confidence interval, CI: 1.89-13.60), P = 0.001], while surgical technique had no significant impact [VATS versus open; OR 0.74 (CI: 0.31-1.78), P = 0.50]. CONCLUSIONS: The number of lymph node stations examined during VATS resections is similar to open resections for cStage-I NSCLC. Almost one-third of the patients with a central cStage-I NSCLC were upstaged to pN1. Tumour location was the only independent variable for pN1 upstaging in logistic regression analysis. It is a potential bias in retrospective studies and should therefore be accounted for when comparing different surgical resection techniques for cStage-I NSCLC.

Thoracoscopic tunnel technique for anatomical lung resections: a 'fissure first, hilum last' approach with staplers in the fissureless patient.

OBJECTIVES: To minimize air leak after anatomical lung resections, many video-assisted thoracic surgery (VATS) surgeons use a 'fissureless' technique, using staplers to divide the hilar bronchovascular structures first and the main part of the fissure last. We describe a cohort of 198 consecutive patients operated with an alternative fissureless technique, opening the fissure completely with staplers at an early stage of the VATS anatomical lung resection. METHODS: To open the incomplete fissure first and with staplers, a tunnel dissection is started anterior between the triangle of pulmonary veins and the parenchyma. After identification of the pulmonary artery, the anvil of a first stapler is placed on top of the artery and the anterior part of the fissure is divided. Dissection between artery and parenchyma is continued until the fissure is completely stapled. From a prospectively managed single institution database, we retrieved 405 patients scheduled for VATS anatomical resection between October 2009 and December 2014. The patients were categorized in four consecutive periods: a learning curve with the first 50 cases of VATS lobectomy technique (LC), a period of consecutive 'hilum first, fissure last' (HF), a transition group (TG) during which both techniques were used and a period of consecutive 'fissure first, hilum last' (FF). RESULTS: No significant differences in operating time, frequency of prolonged air leak or hospital stay were observed between HF (n = 45) and FF (n = 198). Chest tubes were removed earlier in the FF period (6.9 vs 5.2 days, P = 0.025). Excluding the learning curve, we found 2 patients (2.8%) operated 'hilum first' with an intraoperative complication that potentially could have been avoided by a 'fissure first' technique. CONCLUSIONS: By making a tunnel between the bronchovascular structures and parenchyma from anteriorly to posteriorly, one can open the fissure completely with staplers at an early stage of an anatomical lung resection. This combines the advantages of both the 'fissureless' hilum first technique and classic (open) fissure first dissection, i.e. minimal air leak and optimal anatomical overview before bronchovascular structures are divided, potentially avoiding inadvertent transections. A cohort of 198 consecutive patients operated with this alternative fissureless technique demonstrates the feasibility and non-inferiority regarding hospital stay, chest tube duration, operation time and complications in comparison with the hilum first technique.

A decade of extended-criteria lung donors in a single center: was it justified?

Despite a worldwide need to expand the lung donor pool, approximately 75% of lung offers are not accepted for transplantation. We investigated the impact of liberalizing lung donor acceptance criteria during the last decade on the number of effective transplants and early and late outcomes in our center. All 514 consecutive lung transplants (LTx) performed between Jan 2000 and Oct 2011 were included. Donors were classified as matching standard criteria (SCD; n = 159) or extended criteria (ECD; n = 272) in case they fulfilled at least one of the following criteria: age >55 years, PaO2 /FiO2 at PEEP 5 cmH2 O < 300 mmHg at time of offer, presence of abnormalities on chest X-ray, smoking history, presence of aspiration, presence of chest trauma, or donation after circulatory death. Outcome parameters were primary graft dysfunction (PGD) grade at 0, 12, 24, and 48 h after LTx, time to extubation, stay in intensive care unit (ICU), early and late infection, acute rejection and bronchiolitis obliterans syndrome (BOS), and survival. Two hundred and seventy-two recipients (63.1%) received ECD lungs. PGD grade at T0 was similar between groups, while at T12 (<0.01), T24 (<0.01), and T48 (<0.05), PGD3 was observed more often in ECDs. ICU stay (P < 0.05) was longer in ECDs compared with SCDs. Time to extubation, respiratory infections, acute rejection, lymphocytic bronchiolitis, BOS, and survival were not different between groups. Accepting ECDs contributed in increasing the number of lung transplants performed in our center. Although this lung donor strategy has an impact on early postoperative outcome, liberalizing criteria did not influence long-term outcome after LTx.

Do we need to cool the lung graft after ex vivo lung perfusion? A preliminary study.

BACKGROUND: After normothermic ex vivo lung perfusion (EVLP), pulmonary grafts are usually flush-cooled and stored on ice until implantation although evidence for this practice lacks. We compared outcomes between 2 post-EVLP preservation strategies in a porcine left single-lung transplantation model. MATERIAL AND METHODS: After cold flush and 2-h EVLP, donor lungs were prepared and split. In [C], (n = 5) lungs cooled on device to 15°C were preserved in ice-water; in [W] (n = 5), lungs were disconnected from EVLP at 37°C and kept at room temperature. The left lung was transplanted in a recipient animal. Posttransplant, 6 h-monitoring included hourly assessment of pulmonary vascular resistance, pulmonary artery pressure, plateau airway pressure, compliance, and oxygenation before and after exclusion of the right lung. Lung biopsies and bronchoscopy with bronchoalveolar lavage (BAL) were performed at retrieval, at the end of EVLP (R lung), and 1 and 6 h after reperfusion (L lung). RESULTS: Lungs in [W] showed the highest compliance (P < 0.05) and the lowest plateau airway pressure (not statistically significant) throughout the whole reperfusion period. Oxygenation and pulmonary artery pressure were similar between groups. Pulmonary vascular resistance was stable in [C], but rose after reperfusion in [W]. Histologic signs of lung injury and BAL neutrophilia were more pronounced in [C] at 1 h (not statistically significant and P < 0.05, respectively). BAL cytokine levels and lung tissue expression of intercellular adhesion molecule 1 did not differ between groups. CONCLUSIONS: Normothermic preparation after EVLP results in similar graft performances compared with lung cooling after EVLP.