Medical Thoracoscopy and Intrapleural Fibrinolytic Therapy for the Management of Pleural Empyema: A Cohort Study.

BACKGROUND: Pleural empyema is associated with relevant morbidity and mortality, and it may be classified, according to evolution and ultrasound, into three stages: stage I (free-flowing effusion), stage II (viscous effusion with the tendency to loculate), and stage III (organizing phase). According to guidelines, antibiotic therapy and pleural drainage are recommended, with surgery being performed when patients fail and/or in case of organized empyema. OBJECTIVES: The aim of the study was to report the efficacy and safety of medical thoracoscopy in patients with pleural empyema stratified by chest ultrasound. METHOD: Observational retrospective cohort study analyzing patients with pleural empyema treated with medical thoracoscopy. Procedure success and mortality were evaluated at 30 days and 90 days after the procedure; complications were also reported. RESULTS: 131 patients were included. Intrapleural fibrinolytic therapy was performed thereafter in the majority of cases. Medical thoracoscopy was considered successful without subsequent intervention in 99 patients (76%); 19 patients (15%) underwent a second procedure (drainage, thoracoscopy, video-assisted thoracic surgery, or thoracotomy); and 6 patients (5%) died of the evolution of empyema. Patients treated in stages I and II showed significantly better post-procedure results compared with patients treated in stage III (100%, 83.3%, and 58.1%, respectively). Thoracoscopy complications were observed in 18 patients and were reversible in all cases. CONCLUSIONS: Patients with pleural empyema treated in earlier stages (free-flowing or multiloculated effusion) with medical thoracoscopy show significantly better results than patients treated in later stages (organized empyema). This approach is safe, minimally invasive, and efficient in these patients with disease having relevant mortality; however, patient selection remains essential.

Autologous Blood Pleurodesis: What Is the Optimal Time Interval and Amount of Blood?

BACKGROUND: Air leak is the most common complication after lung resection and leads to increased length of hospital (LOH) stay or patient discharge with a chest tube. Management by autologous blood patch pleurodesis (ABPP) is controversial because few studies exist, and the technique has yet to be standardized. METHODS: We retrospectively reviewed patients undergoing ABPP for prolonged air leak (PAL) following lobectomy in three centers, between January 2014 and December 2019. They were divided into two groups: Group A, 120 mL of blood infused; Group B, 60 mL. Propensity score-matched (PSM) analysis was performed, and 23 patients were included in each group. Numbers and success rates of blood patch, time to cessation of air leak, time to chest tube removal, reoperation, LOH, and complications were examined. Univariate and multivariate analysis of variables associated with an increased risk of air leak was performed. RESULTS: After the PSM, 120 mL of blood is statistically significant in reducing the number of days before chest tube removal after ABPP (2.78 vs. 4.35), LOH after ABPP (3.78 vs. 10.00), and LOH (8.78 vs. 15.17). Complications (0 vs. 4) and hours until air leak cessation (6.83 vs. 3.91, range 1-13) after ABPP were also statistically different (p < 0.05). Air leaks that persisted for up to 13 hours required another ABPP. No patient had re-operation or long-term complications related to pleurodesis. CONCLUSION: In our experience, 120 mL is the optimal amount of blood and the procedure can be repeated every 24 hours with the chest tube clamped.

Covid-19 Interstitial Pneumonia: Histological and Immunohistochemical Features on Cryobiopsies.

BACKGROUND: The pathogenetic steps leading to Covid-19 interstitial pneumonia remain to be clarified. Most postmortem studies to date reveal diffuse alveolar damage as the most relevant histologic pattern. Antemortem lung biopsy may however provide more precise data regarding the earlier stages of the disease, providing a basis for novel treatment approaches. OBJECTIVES: To ascertain the morphological and immunohistochemical features of lung samples obtained in patients with moderate Covid-19 pneumonia. METHODS: Transbronchial lung cryobiopsy was carried out in 12 Covid-19 patients within 20 days of symptom onset. RESULTS: Histopathologic changes included spots of patchy acute lung injury with alveolar type II cell hyperplasia, with no evidence of hyaline membranes. Strong nuclear expression of phosphorylated STAT3 was observed in >50% of AECII. Interalveolar capillaries showed enlarged lumen and were in part arranged in superposed rows. Pulmonary venules were characterized by luminal enlargement, thickened walls, and perivascular CD4+ T-cell infiltration. A strong nuclear expression of phosphorylated STAT3, associated with PD-L1 and IDO expression, was observed in endothelial cells of venules and interstitial capillaries. Alveolar spaces macrophages exhibited a peculiar phenotype (CD68, CD11c, CD14, CD205, CD206, CD123/IL3AR, and PD-L1). CONCLUSIONS: Morphologically distinct features were identified in early stages of Covid-19 pneumonia, with epithelial and endothelial cell abnormalities different from either classical interstitial lung diseases or diffuse alveolar damage. Alveolar type II cell hyperplasia was a prominent event in the majority of cases. Inflammatory cells expressed peculiar phenotypes. No evidence of hyaline membranes and endothelial changes characterized by IDO expression might in part explain the compliance and the characteristic pulmonary vasoplegia observed in less-advanced Covid-19 pneumonia.

Pulmonary Metastases from NSCLC and MPLC (Multiple Primary Lung Cancers): Management and Outcome in a Single Centre Experience.

BACKGROUND: This is an institutional review of surgical management of second pulmonary tumours in patients with history of Non-small Cell Lung Cancer (NSCLC) resection according to The American College of Chest Physicians' (ACCP) revision to the Martini and Melamed's criteria for the classification of multiple primary lung cancers (MPLC). METHODS: All patients who underwent iterative pulmonary resections for pulmonary metastasis (Group A) or MPLC (Group B) between 2006 and 2012 were reviewed and their survivals compared accordingly. The main criteria of insertion in Group B were different histology and the same histology with disease-free interval ≤ 4 years; we excluded loco-regional recurrence in nodes and/or on bronchial stump. RESULTS: Group A: Twenty patients; Disease free time (DFT) after first operation was 15.2 months (range 2-44). One, two and three years overall survival after second resection was 74%, 29%, 14% respectively. Group B: Thirty-six patients. One, two and three years overall survival was 94%, 81%, and 69% respectively. No statistical differences on outcome were found between the two groups in spite of the apparent worse survival rate for Group A (p=.197). CONCLUSIONS: A further resection for additional nodules, whether designated as intrapulmonary metastases or second primary NSCLC, can be an appropriate curative strategy in selected patients with unimpaired respiratory function and no evidence of distant metastatic disease. The site, the extent of the second resection, the histology and even the stage are unlikely to be related to survival.

Tracheo-bronchoplastic procedures for NSCLC: single-centre experience.

BACKGROUND: The purpose of this study was to assess operative mortality, morbidity, and long-term results of the totality of sleeve resections performed at our institutions over the last eight years, including sleeve lobectomies (SL), carinoplasties with total lung sparing (CP) and sleeve pneumonectomies (SP). METHODS: A retrospective review of all the patients who underwent a tracheo-bronchial resection for bronchial cancer between 2004 and 2012 was undertaken. Bronchial sleeve resections and combined bronchial and vascular sleeve resections were described. RESULTS: The resulting group studied was 22 patients. SL and SP had a perioperative mortality rate of 7.1% and 28.5% respectively; morbidity rates were 21.4% for SL and 42.8% for SP. Global one-year and three-year survival was 75% and 63% respectively. One-year survival was 84% for SL and 53% for SP; three-year survival rate was 65% and 35% respectively (p=0.24). The absence of nodal metastatic involvement was associated with a better outcome with a three-year survival rate of 69% in the N0 group vs a 36% rate in the N+ group. CONCLUSIONS: Sleeve resection procedures achieved satisfactory local control of the tumour in our experience even in patients with preoperative contraindication to pneumonectomy, with acceptable mortality and morbidity rates.

Synchronous thymoma and lung adenocarcinoma treated with a single mini-invasive approach.

A 75 year-old man with a lesion in the middle lobe of the lung was discovered to also have, during the follow-up period, a mass in the mediastinum, diagnosed as a multi-thymic cyst. Both pathologies were successfully treated with a single surgical approach by video-assisted thoracoscopy. We performed a middle VATS lobectomy with complete lymphadenectomy followed by radical thymectomy without additional incision. The postoperative course was uneventful.

Accuracy of transthoracic ultrasound for the prediction of chest wall infiltration by lung cancer and of lung infiltration by chest wall tumours.

BACKGROUND: We wanted to determine the accuracy of transthoracic ultrasound in the prediction of chest wall infiltration by lung cancer or lung infiltration by chest wall tumours. METHODS: Patients having preoperative CT-scan suspect for lung/chest wall infiltration were prospectively enrolled. Inclusion criteria for lung cancer were: obliteration of extrapleural fat, obtuse angle between tumour and chest wall, associated pleural thickening. The criteria for chest wall tumours were: rib destruction and intercostal muscles infiltration with extrapleural fat obliteration and intrathoracic extension. Lung cancer patients with evident chest wall infiltration were excluded. Transthoracic ultrasound was preoperatively performed. Predictions were checked during surgical intervention. RESULTS: Twenty-three patients were preoperatively examined. Sensitivity, specificity, positive and negative predictive values of transthoracic ultrasound were 88.89%, 100%, 100% and 93.3%, respectively. Youden index was used to determine the best cut-off for tumour size in predicting lung/chest wall infiltration: 4.5cm. At univariate logistic regression, tumour size (<4.5 vs ≥ 4.5cm) (p=0.0072) was significantly associated with infiltration. CONCLUSIONS: Transthoracic ultrasound is a useful instrument for predicting neoplastic lung or chest wall infiltration in cases of suspect CT-scans and could be used as part of the preoperative workup to assess tumour staging and to plan the best surgical approach.

Surgery for non-small cell lung cancer in younger patients: what are the differences?

BACKGROUND: Non-small cell lung cancer (NSCLC) in young adults is uncommon. The objective of this study was to evaluate the clinicopathological characteristics, outcomes and prognosis of people younger than 50 years old treated surgically for NSCLC. METHODS: A retrospective study was conducted using the institutional database of four thoracic surgery units to collect patients with NSCLC younger than 50 years who had undergone surgery. These patients were compared with older patients (>75-years) operated in the same institutions and in the same period. RESULTS: We identified 113 young patients and 347 older patients. Younger patients were more likely to be female, non-smokers, with fewer comorbidities. Younger patients were more likely to be symptomatic at the time of diagnosis. Risk factors for poor prognosis in younger patients were T-stage, and disease-free-interval less than 548 days. Kaplan-Meier analysis showed a lower five-year survival in older patients compared with the younger ones (66% vs 38%, p=0.001). CONCLUSIONS: In conclusion NSCLC in younger patients has some distinct clinicopathological characteristics. The overall-survival of young patients is better than in older patients. Young patients receive more complete and aggressive treatment that could explain better survival. Further prospective studies with larger patient populations are required, to clarify the biological and genetic variance of NSCLC in younger patients.

Treatment strategy for rectal cancer with synchronous metastasis: 65 consecutive Italian cases from the Bologna Multidisciplinary Rectal Cancer Group.

BACKGROUND: Twenty percent of rectal cancer patients have synchronous distant metastasis at diagnosis. At present, the treatment strategy in this patient setting is not well defined. This study in one institution evaluates the treatment strategy of three different patient groups. PATIENTS AND METHODS: Between January 2000 and July 2011, 65 patients with M1 rectal cancer were evaluated. Three different groups were defined: rectal cancer with resectable metastatic disease (group A); rectal cancer with potentially resectable metastatic disease (group B), and rectal cancer with unresectable metastatic disease (group C). RESULTS: Group A included 11 patients (16.9%), group B 28 patients (43.1%) and group C 26 patients (40%). Forty-three (66.2%) patients underwent surgery for primary rectal cancer, and 30 (46.2%) patients for metastasis resection (23 liver, 4 lung and 3 ovary). Median overall survival (OS) by group was: 51 (5-86; group A), 32 (24-40; group B) and 16 (7-26; group C) months. Patients undergoing metastasis resection have higher median OS than unresected patients (44 vs. 15 months; p < 0.001). CONCLUSIONS: The treatment strategy in synchronous metastatic rectal cancer must consider the possibility of distant metastasis resection. Long-term survival can be achieved using an integrated approach.

Circulating cell-free and extracellular vesicles-derived microRNA as prognostic biomarkers in patients with early-stage NSCLC: results from RESTING study.

BACKGROUND: Factors to accurately stratify patients with early-stage non-small cell lung cancer (NSCLC) in different prognostic groups are still needed. This study aims to investigate 1) the prognostic potential of circulating cell-free (CF) and extracellular vesicles (EVs)-derived microRNA (miRNAs), and 2) their added value with respect to known prognostic factors (PFs). METHODS: The RESTING study is a multicentre prospective observational cohort study on resected stage IA-IIIA patients with NSCLC. The primary end-point was disease-free survival (DFS), and the main analyses were carried out separately for CF- and EV-miRNAs. CF- and EV-miRNAs were isolated from plasma, and miRNA-specific libraries were prepared and sequenced. To reach the study aims, three statistical models were specified: one using the miRNA data only (Model 1); one using both miRNAs and known PFs (age, gender, and pathological stage) (Model 2), and one using the PFs alone (Model 3). Five-fold cross-validation (CV) was used to assess the predictive performance of each. Standard Cox regression and elastic net regularized Cox regression were used. RESULTS: A total of 222 patients were enrolled. The median follow-up time was 26.3 (95% CI 25.4-27.6) months. From Model 1, three CF-miRNAs and 21 EV-miRNAs were associated with DFS. In Model 2, two CF-miRNAs (miR-29c-3p and miR-877-3p) and five EV-miRNAs (miR-181a-2-3p, miR-182-5p, miR-192-5p, miR-532-3p and miR-589-5p) remained associated with DFS. From pathway enrichment analysis, TGF-beta and NOTCH were the most involved pathways. CONCLUSION: This study identified promising prognostic CF- and EV-miRNAs that could be used as a non-invasive, cost-effective tool to aid clinical decision-making. However, further evaluation of the obtained miRNAs in an external cohort of patients is warranted.

Desmoid tumour of the thoracic outlet in a 70 year-old man successfully removed through cervico-thoracic Dartevelle approach.

Desmoid tumours have a strong tendency for local invasion and recurrence. A 70 year-old male presented with cervical and left shoulder pain associated with a supraclavicular mass. The computed-tomography showed an expansive lesion measuring 10 cm × 6 cm × 5.5 cm in the left supraclavicular space. At magnetic resonance imaging the subclavian vessels and the brachial plexus were dislocated anteriorly but not infiltrated. An incisional biopsy suggested a desmoid tumour. An anterior cervicothoracic approach was used to remove the tumour. The chest wall was reconstructed with titanium bars and a polytetrafluoroethylene-patch. The clavicle was fixed using a titanium clip. The post-operative course was uneventful. The patient was treated with adjuvant radiation therapy. After six months the patient is in good clinical condition free from disease recurrence. In conclusion, desmoid tumour of the thoracic outlet is a challenging situation. Wide radical resection should be attempted whenever possible. The Dartevelle approach gives an optimal surgical field with direct control of vessels and nerve roots facilitating tumour dissection and radical resection en-bloc with the chest wall. The chest wall reconstruction with titanium bars and clips is a simple and effective method to guarantee good respiratory function and to stabilise the shoulder girdle.

Sternal resection and reconstruction for local recurrence of breast cancer using the sternal allograft transplantation technique.

Sternal involvement in patients with breast cancer is relatively rare and its treatment is still controversial. Surgery is usually indicated in cases of single metastases in a multimodality protocol. Partial or complete sternectomy associated or not with the resection of surrounding tissues is the technique of choice to obtain safety margins and radical treatment of the disease. The most challenging part of the operation is the reconstruction of the anterior chest wall in order to avoid secondary complications and respiratory failure. In the last few years, different techniques and materials have been used to reconstruct the sternum. We report our experience in two patients with recurrent breast cancer using the sternal allograft technique to replace the sternum after partial sternectomy. The use of a sternal-allograft provides excellent functional and cosmetic results without complications during the follow-up period. The implantation technique is simple and reproducible.

Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches.

Lung cancer (LC) is the second most common neoplasm in men and the third most common in women. In the last decade, LC therapies have undergone significant improvements with the advent of immunotherapy. However, the effectiveness of the available treatments remains insufficient due to the presence of therapy-resistant cancer cells. For decades, chemotherapy and radiotherapy have dominated the treatment strategy for LC; however, relapses occur rapidly and result in poor survival. Malignant lung tumors are classified as either small- or non-small-cell lung carcinoma (SCLC and NSCLC). Despite improvements in the treatment of LC in recent decades, the benefits of surgery, radiotherapy, and chemotherapy are limited, although they have improved the prognosis of LC despite the persistent low survival rate due to distant metastasis in the late stage. The identification of novel prognostic molecular markers is crucial to understand the underlying mechanisms of LC initiation and progression. The potential role of phosphatidylinositol in tumor growth and the metastatic process has recently been suggested by some researchers. Phosphatidylinositols are lipid molecules and key players in the inositol signaling pathway that have a pivotal role in cell cycle regulation, proliferation, differentiation, membrane trafficking, and gene expression. In this review, we discuss the current understanding of phosphoinositide-specific phospholipase enzymes and their emerging roles in LC.

Oligometastatic breast cancer and metastasis-directed treatment: an aggressive multimodal approach to reach the cure.

Metastatic breast cancer (BC) is considered an incurable disease and is usually treated with palliative intent. However, about 50% of metastatic BCs present with only a few metastatic lesions and are characterized by longer overall survival. These patients, defined as oligometastatic, could benefit from a multimodal approach, which combines systemic therapy with metastasis-directed treatment (stereotactic ablative therapy or surgery). The current definition of oligometastatic seems incomplete since it is based only on imaging findings and does not include biological features, and the majority of relevant data supporting this strategy comes from retrospective or non-randomized studies. However, the chance of reaching long-term complete remission or even a cure has led to the development of randomized trials investigating the impact of combined treatment in oligometastatic BC (OMBC). The SABR-COMET trial, the first randomized study to include BC patients, showed promising results from a combination of stereotactic ablative radiotherapy and systemic therapy. Considering the randomized trial's results, multidisciplinary teams should be set up to select OMBC patients who could achieve long-term survival with aggressive multimodal treatment.

A massive post-sternotomy sternal defect treated by allograft sternal transplantation.

We report a case of a patient with complete sternal destruction after cardiac surgery, who underwent total sternal replacement with sternal allograft, titanium bars, and screws.

Can topical application of tranexamic acid reduce blood loss in thoracic surgery? A prospective randomised double blind investigation.

OBJECTIVE: The systemic or topical use of antifibrinolytic agents is effective in reducing postoperative bleeding and blood product transfusion in cardiac surgery. We sought to study the effect of the topical application of tranexamic acid into the pleural space to reduce postoperative bleeding after lung surgery. METHODS: This was a prospective randomised double blind placebo controlled investigation. From May-2010 to February-2012, 89-patients, scheduled for pulmonary resection, were randomly allocated to one of the two study groups. Group-A received 5 g of tranexamic-acid in 100 ml of saline solution. Group-B received 100 ml of saline solution as placebo. RESULTS: The blood loss in the first 12-h was significantly less in group-A. The same trend was observed in the first 24-h but without reaching a true statistical significance. The mean volume of blood transfusion was statistically lower in group-A. The analysis between post-operative haemoglobin concentration, haematocrit, platelet-count, international-normalised-ratio, fibrinogen and partial-thromboplastin-time of both groups was not statistically significant. CONCLUSION: In our experience, the topical use of tranexamic-acid after lung surgery reduces postoperative bleeding and blood transfusion volume. The topical administration of tranexamic-acid is safe without increasing the risk of post-operative complications related to pharmacological side-effects.

Tracheal reconstruction: mini-review and anatomical study on the use of antero lateral thigh fascial flap for heterotopical transplantation.

Background: The reconstructive tracheal options for extensive lesions still remain limited and although a valid substitute is required unfortunately, the biomechanical tracheal characteristics do not allow an easy replacement. In this study we reviewed the described options and investigated, in human cadaver model, whether thigh fascia can be used, as an alternative to forearm fascia, as recipient site for trachea graft heterotopical allotransplantation. Anatomical study: In three fresh cadavers, 3 tracheal graft, 6 radial forearm (RF) fascial flaps and 6 antero-lateral thigh (ALT) fascial flaps were harvested. For each flap we simulated the heteretopical transplantation of the trachea in each fascial flap, and the harvesting of the composite graft as a free flap. The composite graft was finally decomposed at bench and the pedicle was injected to confirm fascial vascularization. The main measured outcomes were: flap fascia vascularization after pedicle injection, average time of flap harvesting, number of perforators included in ALT fascial flap and diameter of the vessels for anastomosis. Difficulties were noted, in order to compare RF flap and ALT flap. Results: Fascia vascularization was confirmed in all cases by pedicle injection. The main difficulty with radial flap was to harvest the fascial layer due to its thinness and its strong adherence to palmaris longus tendon, while the main difficulty with ALT flap was to prevent any traction on the perforators. The average time of flap harvesting and graft inset (by a junior plastic surgeon) was 1 h and 30 min for radial forearm flap and 2 h and 10 min for ALT flap. Conclusion: Despite many different techniques proposed in the literature, tracheal heterotopical allotransplantation still seemed the most promising, and ALT flap promised be a feasible alternative for heterotopical transplantation of trachea.

Second Surgery for Recurrent Malignant Pleural Mesothelioma after Multimodality Treatment: A Systematic Review.

Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumour with poor prognosis. To date, a multimodality treatment, including chemotherapy and surgery, with or without radiotherapy, is the gold standard therapy for selected patients with epithelioid and early-stage MPM. In this setting, the goal of surgery is to achieve the macroscopic complete resection, obtained by either extrapleural pneumonectomy or pleurectomy/decortication. Failure, in local and/or distant sites, is one of the major concerns; in fact, there has been no established treatment for the recurrence of MPM after the multimodal approach, and the role of surgery in this context is still controversial. By using electronic databases, studies that included recurrent MPM patients who underwent a second surgery were identified. The endpoints included were: a pattern of recurrence, post-recurrence survival (PRS), and the type of second surgery. When available, factors predicting better PRS and perioperative mortality and morbidity were collected. This systematic review offers an overview of the results that are currently obtained in patients undergoing a second surgery for relapsed MPM, with the aim to provide a comprehensive view on this subject that explores if a second surgery leads to an improvement in survival.

Comparative Analysis of Free-Circulating and Vesicle-Associated Plasma microRNAs of Healthy Controls and Early-Stage Lung Cancer Patients.

In recent years, circulating extracellular miRNAs have emerged as a useful tool for the molecular characterization and study of tumors' biological functions. However, the high heterogeneity in sample processing, isolation of circulating fraction, RNA extraction, and sequencing hamper the reproducibility and the introduction of these biomarkers in clinical practice. In this paper, we compare the content and the performance of miRNA sequencing in plasma-derived samples processed with different isolation protocols. We tested three different fractions of miRNA from healthy-donor human blood: whole plasma (WP), free-circulating (FC) and EV-associated, isolated by either column (ccEV) or size exclusion chromatography (secEV) miRNAs. An additional cohort of 18 lung cancer patients was analyzed. Protein profiles of ccEV and secEV were compared and miRNA expression profiles were assessed through sequencing. Slight differences were found between ccEV and secEV expressions of typical EV markers. Conversely, sequencing performance and the mirnome profile varied between RNA extracted using different isolation methods. Sequencing performance was better in FC samples. Higher varieties of miRNAs were identified in WP and FC with respect to ccEV and secEV. Analysis of free-circulating and EV-associated miRNA profiles in lung cancer patients demonstrated the reliability of the biomarkers identifiable on plasma with these approaches.