Assessment of the 90-day mortality risk score after video-assisted thoracoscopic lobectomy in the Italian VATS Group cohort.

A five classes (A-E) aggregate risk score predicting 90-day mortality after video-assisted thoracoscopic lobectomy for lung cancer, including as independent factors male sex (3 points), DLCO <60% (1 point) and operative time >150 minutes (1 point), has been recently published. This study aims to assess the effectiveness and reliability of this risk model in a large, independent cohort of patients, to confirm its generalizability. From the Italian VATS Group Database, we selected 2,209 patients [60% males; median age 69 years (IQR:63-74)] who underwent video-assisted thoracoscopic lobectomy for non-small cell lung cancer. We calculated the aggregate risk score and the corresponding class of 90-day mortality risk for each patient. The correlation between risk classes and mortality rates was tested by Spearman's r-test. Model calibration was evaluated by Hosmer-Lemeshow goodness-of-fit test. Class A-E 90-day mortality rates were 0.33%, 0.51%, 1.39%, 1.31% and 2.56%, respectively. A strong uphill correlation was identified between risk classes and 90-day mortality (r=0.90; p=0.037), showing a positive correlation between increased mortality rate and class A to E. Hosmer-Lemeshow chi-squared value was 67.47 (p<0.001) with overall, Class D and E significantly lower 90-day mortality in our cohort than in the original one [1.04% vs 2.5% (p=0.018), 1.31% vs 5.65% (p=0.005) and 2.56% vs 18.75% (p=0.007), respectively]. Despite our data show a positive correlation between 90-day mortality and risk classes from A to E with modest discriminatory performance, the poor calibration suggests the need for model recalibration using local data to better manage and counsel lung cancer patients eligible for video-assisted thoracoscopic lobectomy.

Accuracy of 18F-FDG in Detecting Stage I Lung Adenocarcinomas According to IASLC/ATS/ERS Classification.

BACKGROUND: Only a small number of studies have explored the clinicopathological features of pulmonary adenocarcinoma (PA) associated with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) false-negative (FN) results. Herein, we investigated the FDG-PET diagnostic performance by stratifying PAs according to International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. METHODS: From January 2002 to December 2016, all consecutive patients who underwent pulmonary resection for stage I PA at six thoracic surgery institutions were retrospectively reviewed. The diagnostic performance of FDG-PET was analysed according to IASLC/ATS/ERS classification and two validated subclassifications. Univariable and multivariable logistic analysis were used to identify predictors of FDG-PET FN results. RESULTS: Five hundred and fifty (550) patients with stage I PA were included in the analyses. Most of the patients were male (n=354 [64.4%]) and smokers (n=369 [67.1%]). Ninety-seven (n=97 [17.6%]) FN cases were observed at FDG-PET imaging. On multivariable analysis, a lepidic pattern was found to be independently associated with FDG-PET FN results (odds ratio [OR], 3.20; p<0.001), while a solid pattern more commonly presented with a positive finding (OR, 0.40; p=0.066). According to Nakamura's classification, we observed an independent association between lepidic pattern and FDG-PET FN results (OR, 3.17; p<0.001), while solid/micropapillary patterns were independently related with increased FDG uptake (OR, 0.35; p=0.021). According to Yoshizawa's classification, Intermediate-grade tumours were independently correlated with FN FDG-PET results (OR, 2.78; p=0.005). CONCLUSIONS: In our cohort, histopathological features were significantly associated with FDG uptake. In particular, some adenocarcinoma subtypes (mostly Lepidic pattern) have a tendency towards FN FDG-PET findings. The correlation between computed tomography findings, clinical characteristics, and FDG uptake is mandatory, in order to tailor the precise diagnostic and therapeutic pathway for each patient.

Genome-wide expression of the residual lung reacting to experimental Pneumonectomy.

BACKGROUND: Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq). RESULTS: Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjusted P-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs were Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs were Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of "Extrinsic apoptotic signaling pathway" (FDR q = 7.60 × 10- 3) and "Response to insulin" (FDR q = 7.60 × 10- 3) genes, along with an enrichment of genes involved as "Negative regulators of DDX58/IFIH1 signaling" (FDR q = 7.50 × 10- 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections. CONCLUSION: This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.

Kynurenine/Tryptophan Ratio as a Potential Blood-Based Biomarker in Non-Small Cell Lung Cancer.

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) degrade tryptophan (Trp) into kynurenine (Kyn) at the initial step of an enzymatic pathway affecting T cell proliferation. IDO1 is highly expressed in various cancer types and associated with poor prognosis. Nevertheless, the serum Kyn/Trp concentration ratio has been suggested as a marker of cancer-associated immune suppression. We measured Kyn and Trp in blood samples of a wide cohort of non-small-cell lung cancer (NSCLC) patients, before they underwent surgery, and analyzed possible correlations of the Kyn/Trp ratio with either IDO1 expression or clinical-pathological parameters. Low Kyn/Trp significantly correlated with low IDO1 expression and never-smoker patients; while high Kyn/Trp was significantly associated with older (≥68 years) patients, advanced tumor stage, and squamous cell carcinoma (Sqcc), rather than the adenocarcinoma (Adc) histotype. Moreover, high Kyn/Trp was associated, among the Adc group, with higher tumor stages (II and III), and, among the Sqcc group, with a high density of tumor-infiltrating lymphocytes. A trend correlating the high Kyn/Trp ratio with the probability of recurrences from NSCLC was also found. In conclusion, high serum Kyn/Trp ratio, associated with clinical and histopathological parameters, may serve as a serum biomarker to optimize risk stratification and therapy of NSCLC patients.

Is Myotomy Plus Diverticulopexy Suitable for Symptomatic Zenker's Diverticula?

The aim of the study was to prospectively evaluate the outcome of myotomy plus diverticulopexy over short and long-terms. A prospectively collected consecutive series (2007-2017) of 37 patients undergoing myotomy plus diverticulopexy was analyzed for clinical condition, operative information, peri-operative events, and follow-up by means of interview and physical examination. Diverticulopexy was scheduled regardless of the diverticulum's features and patient condition, other than operability. There was no choice or selection between possible treatment options. Patients were evaluated pre-operatively, at post-operative day 30 and after 1 year. Follow-up aimed at assessing the subjective condition following treatment. During the interview, patients were asked to self-assess their ability to swallow before and after surgery. No patient had peri-operative events, complications associated with the procedure, wound infection or impaired swallowing. All patients could start drinking the day after operation, could return to solid diet on post-operative day 2 and be discharged on post-operative days 3-4. Barium swallowing was not necessary before discharge. Full solid diet was resumed according to patient's compliance from post-operative day 2 (some patients refused solid diet soon after the operation even if asymptomatic). Follow-up ranged between 1 and 8 years. No patient was lost at follow-up. No disease recurrence was observed. Finally, no patient needed or sought for a clinical examination between the follow-up calls. Patients reported at least 50% improvement of symptomatology after 1 year. Diverticulopexy appears to be clinically safe, methodologically reproducible, and an effective procedure; it avoids suturing and offers good outcome results along with high patient satisfaction.

Stage-related outcome for thymic epithelial tumours.

BACKGROUND: Thymic epithelial tumours (TETs) are characterized by a wide variety of biological behaviors. Radical resection and stage are strong prognostic factors. Aim of this study is to review our Single Center Experience. METHODS: One hundred and seventy-seven patients observed in the period from January 2000 to December 2016 were included in the study. Data regarding clinicopathologic features, treatment, and survival were collected. Stage-related clinical standpoints and therapeutic options were also evaluated. RESULTS: Non-surgical treatment was primarily performed in 15 (8.47%), unresectable disease was intraoperatively found in 12 cases (7.4%). The analysis of 150 patients undergoing curative surgery revealed 70 stage I TET (46.66%), 49 stage II (32.66%), 19 stage III (12.66%), 6 stage IVa (4%) and 6 stage IVb (4%) at the first hospital admission. Histology identified 12 A thymoma (8%), 38 AB (25.33%), 24 B1 (16%), 50 B2 (33.33%), 19 B3 (12.66%) and 7 carcinomas (4.66%). The mean follow up time was 84.14 months (sd = 61.68 months). Disease relapse occurred in 13 patients (8.78%) at a mean period of 78.85 months (sd = 60.87 months) after surgery. Exitus due to thymoma happened in 6 cases (4.05%) after a mean survival of 56.02 months (sd = 25.17 months). The 5-year overall survival rate was 0.94 (95%CI 0.88-0.97) and the 5-year disease-free survival rate was 0.90 (95%CI 0.83-0.94). The 5-year overall survival rates were 96.1% (95% CI, 89.9-98.5%) for the early stages and 87.4% (95% CI, 65.6-95.8%) for the advanced stages (p = 0.670). The 5-year disease-free survival rates resulted being 98.8% (95% CI, 92.3-99.8%) for the early stages and 59.8% (95% CI, 37.8-76.2%) for the advanced stages (p < 0.001). CONCLUSIONS: Advanced stage TETs are characterized by higher mortality and recurrence rates. Although technically demanding, surgery, as part of multimodality therapy, could prolong survival. Iterative surgical treatment of recurrences is a viable option for selected patients. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Perugia and Terni University Hospitals [Code T1003] and was retrospectively registered.

Pericardium matrix buttressing hinders the stapled bronchial stump healing.

BACKGROUND: Biomechanical and histological properties of stapled bronchi with and without bovine pericardial matrix plus collagen reinforcement are analyzed. MATERIALS AND METHODS: Pneumonectomy with mechanical bronchial suture was performed in the swine model. Pigs were randomly assigned to three groups: three-row staplers without reinforcement (Traditional), with reinforcement (Buttressed) and control "wild type", non-resected normal bronchus (Normal). Intraoperative test was carried for air leaks at 20/30/40 mm Hg endobronchial pressure. After 60 d, tracheobronchial specimen was harvested, stocked, and analyzed. Tensile test was performed using INSTRON 5965 loading frame machine. Maximal strain resistance value, length of elongation at rupture parameter, and stiffness coefficient (K) were evaluated. Histological analysis was performed. Sample size calculation was assessed (four per group), and the Student t-test was used to statistically evaluate differences in biomechanical variables. RESULTS: No fistula occurred. Biomechanical analysis showed that maximal strain resistance is 41.22 ± 2.11 N (Traditional), 24.53 ± 3.47 N (Buttressed), and 30.91 ± 0.29 N (Normal); elongation at rupture is 16.01 ± 1.82 mm (Traditional), 12.89 ± 0.48 mm (Buttressed), and 9.32 ± 0.11 mm (Normal). Finally, K is 2.59 ± 0.16 N/mm (Traditional), 1.91 ± 0.33 N/mm (Buttressed), and 3.32 ± 0.01 N/mm (Normal). Stumps without reinforcement proved higher resistance and length of elongation than reinforced ones. Normal bronchial tissue shows the highest stiffness coefficient. Statistical analysis produced significant values for each biomechanical feature. Group Buttressed stumps show greater thickness and a substantial inflammatory reaction with granulation tissue along the whole scar and around areas of discontinuity within the scar, not yet healed. CONCLUSIONS: Reinforcing the mechanical suture line of bronchial stump with bovine pericardial matrix plus collagen shows suboptimal biomechanical and histological characteristics compared to using the stapler alone.

Pleurodesis with Thulium Cyber Laser versus talc poudrage: a comparative experimental study.

Sclerosing fluids to achieve pleurodesis could be hardly replaced for bed-side procedures, but other devices may be successfully applied during thoracoscopy. Thulium Cyber Laser was experimented for this purpose and compared to talc poudrage. Twenty pigs underwent operative videothoracoscopy (VATS). Ten models were subjected to double-port VATS and parietal pleura photoevaporation using Thulium Cyber Laser™ (TCL) 150 W 2010 nm on the posterior third of three ribs; the pleural surface was homogeneously treated inside the target perimeter. The remaining ten pigs underwent uniportal thoracoscopy; talc poudrage was performed using the current clinical practice dosage (1 g/18 kg) with accurate talc powder spread over the whole pleural surface. All models were followed up for 60 days. Pleurodesis firmness was graded on a three-tier scale (none-moderate-firm) and site-matching topographical expectancy was evaluated. TCL produced pleurodesis in all models: 7/10 were firm and 3/10 moderate. Talc poudrage pleurodesis was firm in 4/10 and moderate in 6/10. Pleural adhesions were found exclusively in the treated area after laser treatment, while talc created a wide spectrum of effects, most commonly anarchic jagged adhesions obliterating less than 50 % of the pleural cavity (7/10), mostly declivous. The pathologist found more aggressive inflammation (sometimes severe) in the talc group. Expected localized pleurodesis was always registered in laser group (10/10), while talc poudrage was found poorly effective if consistent pleurodesis is expected in an apico-dorsal position (2/10). Laser pleurodesis appears more homogeneous, qualitatively not inferior, and topographically more predictable than talc pleurodesis. Parietal photoevaporation seems effective and the localized pleurodesis is reproducible.

Experimental left pneumonectomy in pigs: procedure and management.

BACKGROUND: Because there is no detailed description of procedures and perioperative management of major pulmonary resections in swine, we reviewed our experience to delineate the most effective practice in performing left pneumonectomy. MATERIALS AND METHODS: Analysis of 11 consecutive left pneumonectomies. Animal data, operative reports, anesthesia records, and perioperative facts were evaluated. Follow-up information until postoperative day 60, methods of care-taking, therapy administration, and all the stabling aspects were systematically assessed. The investigation was aimed at highlighting those procedural steps or details which make the difference in optimizing the available resources (animals, instruments, and personnel). No statistical analysis was performed considering data characteristics and the descriptive nature of information. RESULTS: Surgery requires a median time of 2 h and 16 min; two operators and one anesthesiologist represent the basic team. Circulators' number depends on goals to accomplish. The most straightforward procedure requires careful dissection of the pulmonary ligament (limited view), pulmonary veins (low variability), pulmonary artery (delicate), and finally bronchus (no variability observed). The key factors for good anesthesia management have been identified: sedation by caregivers, preoxygenation before induction of general anesthesia, high respiratory rates with low tidal volume after pneumonectomy, and noninvasive ventilation after extubation. Antibiotic prophylaxis has been performed. Postoperative care must be continuous until animals are able to stand up, afterward "preventive noncurative," and always animal friendly. Ideas for minimally stressful therapy administration are helpful. CONCLUSIONS: After the delineation of this methodology, the compliance to a routine practice allowed us to reduce time, stress, and cost; quality and quantity of possible research increased.

Aneurysmal artery supplying pulmonary sequestration: successful combined approach.

A 62-year-old man was diagnosed with an asymptomatic intralobar pulmonary sequestration supplied by a short-neck proximal 57×25 mm aneurysmal artery originating from the mid-descending aorta. The patient underwent thoracic endovascular aneurysm repair; an aortic endograft was released to entirely restore the aberrant vessel. Then, pulmonary resection was performed. A triportal video-assisted left lower lobectomy was carried out. The thoracic endovascular aneurysm repair minimized the risk of bleeding and allowed a safe pulmonary resection with a minimally invasive approach.

Phrenoplasty Techniques for the Reconstruction of Basal Chest Wall Defects.

BACKGROUND: Primary and secondary tumors of the abdominal lower third of the bony thorax are relatively rare. Therefore, indications and techniques for chest wall reconstructions in this area are not well defined. METHODS: The techniques for reconstructing basal chest wall defects using the diaphragm are described. Indications for phrenoplasty are limited to reconstruction after full-thickness resection of at least two of the last four ribs in the midaxillary line. The diaphragm can be used for reconstructive purposes both if it is intact and if it is partially involved in the resection of the chest wall. RESULTS: At our institution, the abovementioned reconstructive technique was successfully performed in five patients with an uneventful post-operative course. CONCLUSIONS: The main advantages of these methods are the use of promptly available, high-quality autologous tissue and the exclusion of the pleural space from the defect area, thus transforming a thoracic defect into an abdominal one. The disadvantage is a variable reduction in the volume of the hemithorax. These techniques could be compared with other reconstruction techniques using pre-/post-operative respiratory functional tests.

Bioinformatics identification of characteristic genes of cervical cancer via an artificial neural network.

BACKGROUND: Artificial neural networks (ANNs) have been extensively used in the field of medicine. The present hypothesis-free study sought to use an ANN to identify the characteristic genes of cervical cancer (CC). METHODS: RNA sequencing profiles were obtained from the GSE7410, GSE9750, GSE63514, and GSE52903 datasets. The differentially expressed genes (DEGs) were identified and compared between the normal and CC tissues. An ANN analysis was conducted to obtain the random-forest tree and to examine differences in gene filtering. A neural network model was established using the characteristic genes of CC, while the verification accuracy of the model was examined by Cox regression. The differences in the immune infiltrating cells between the normal cervical and CC tissues were compared by CIBERSORT (an analytical tool can provide an estimation of the abundances of member cell types in a mixed cell population). RESULTS: Nine genes' characteristics for CC were identified: cyclin-dependent kinase inhibitor 2A (CDKN2A), chromosome 1 open reading frame 112 (C1orf112), helicase, lymphoid-specific (HELLS), mini-chromosome maintenance protein 5 (MCM5), mini-chromosome maintenance protein 2 (MCM2), kinetochore associated 1 (KNTC1), cysteine-rich secretory protein 3 (CRISP3), phytanoyl-CoA 2-hydroxylase interacting protein (PHYHIP), and cornulin (CRNN). CONCLUSIONS: ANN is a robust neural network model that can be used to potentially predict CC based on the gene score. It can provide novel insights into the pathogenesis and molecular mechanisms of CC.

Lung Cancer Surgery in Octogenarians: Implications and Advantages of Artificial Intelligence in the Preoperative Assessment.

The general world population is aging and patients are often diagnosed with early-stage lung cancer at an advanced age. Several studies have shown that age is not itself a contraindication for lung cancer surgery, and therefore, more and more octogenarians with early-stage lung cancer are undergoing surgery with curative intent. However, octogenarians present some peculiarities that make surgical treatment more challenging, so an accurate preoperative selection is mandatory. In recent years, new artificial intelligence techniques have spread worldwide in the diagnosis, treatment, and therapy of lung cancer, with increasing clinical applications. However, there is still no evidence coming out from trials specifically designed to assess the potential of artificial intelligence in the preoperative evaluation of octogenarian patients. The aim of this narrative review is to investigate, through the analysis of the available international literature, the advantages and implications that these tools may have in the preoperative assessment of this particular category of frail patients. In fact, these tools could represent an important support in the decision-making process, especially in octogenarian patients in whom the diagnostic and therapeutic options are often questionable. However, these technologies are still developing, and a strict human-led process is mandatory.

Xanthoma of rib: a case report and review of the literature.

BACKGROUND: Xanthomas are well-circumscribed benign proliferative lesions seen mainly in soft tissues. Usually, they are found in hyperlipidemia and familial hyperlipoproteinemia. Histologically, are characterized by macrophage-like mononuclear cells, multinucleated giant cells and abundant foam cells. The bone involvement, however, is notoriously rare and rib localization is extremely rare. CASE PRESENTATION: A 55-year-old man performed a chest X-ray and a subsequent chest Computed Tomography scan showing a rib lesion that was surgically removed and a diagnosis of rib xanthoma was made. The patient presented an unknown condition of hyperlipidemia. CONCLUSION: Rib xanthoma can be discovered accidentally and can be helpful in identifying an unrecognized condition of hyperlipidemia.

Concomitant Intubation with Minimal Cuffed Tube and Rigid Bronchoscopy for Severe Tracheo-Carinal Obstruction.

BACKGROUND: Our aim was to report on the use of an innovative technique for airway management utilizing a small diameter, short-cuffed, long orotracheal tube for assisting operative rigid bronchoscopy in critical airway obstruction. METHODS: We retrospectively reviewed the clinical data of 36 patients with life-threatening critical airway stenosis submitted for rigid bronchoscopy between January 2008 and July 2021. The supporting ventilatory tube, part of the Translaryngeal Tracheostomy KIT (Fantoni method), was utilized in tandem with the rigid bronchoscope during endoscopic airway reopening. RESULTS: Indications for collateral intubation were either tumors of the trachea with near-total airway obstruction (13), or tumors of the main carina with total obstruction of one main bronchus and possible contralateral involvement (23). Preliminary dilation was necessary before tube placement in only 2/13 patients with tracheal-obstructing tumors (15.4%). No postoperative complications were reported. There was one case of an intraoperative cuff tear, with no further technical problems. CONCLUSIONS: In our experience, this innovative method proved to be safe, allowing for continuous airway control. It enabled anesthesia inhalation, use of neuromuscular blockage and reliable end-tidal CO2 monitoring, along with protection of the distal airway from blood flooding. The shorter time of the procedure was due to the lack of need for pauses to ventilate the patient.