Management of COVID-19 related tracheal stenosis: The state of art.

Tracheal stenosis (TS) is a debilitating disease promoted by pathologic narrowing of the trachea. The acute respiratory distress syndrome caused by COVID-19 has been demonstrated to trigger enhanced inflammatory response and to require prolonged invasive mechanical ventilation as well as high frequency of re-intubation or emergency intubation, thus increasing the rate and complexity of TS. The standard-of-care of COVID-19-related tracheal complications has yet to be established and this is a matter of concern. This review aims at collecting latest evidence on this disease, providing an exhaustive overview on its distinctive features and open issues, and investigating different diagnostic and therapeutic strategies to handle COVID-19-induced TS, focusing on endoscopic versus open surgical approach. The former encompasses bronchoscopic procedures: electrocautery or laser-assisted incisions, ballooning dilation, submucosal steroid injection, endoluminal stenting. The latter consists of tracheal resection with end-to-end anastomosis. As a rule, traditionally, the endoscopic management is restricted to short, low-grade, and simple TS, whereas the open techniques are employed in long, high-grade, and complex TS. However, the critical conditions or extreme comorbidities of several COVID-19 patients, as well as the marked inflammation in tracheal mucosa, have led some authors to apply endoscopic management also in complex TS, recording acceptable results. Although severe COVID-19 seems to be an issue of the past, its long-term complications are still unknown and considering the increased rate and complexity of TS in these patients, we strongly believe that it is worth to focus on it, attempting to find the best management strategy for COVID-19-related TS.

Post-intubation iatrogenic tracheobronchial injuries: The state of art.

Iatrogenic tracheobronchial injury (ITI) is an infrequent but potentially life-threatening disease, with significant morbidity and mortality rates. Its incidence is presumably underestimated since several cases are underrecognized and underreported. Causes of ITI include endotracheal intubation (EI) or percutaneous tracheostomy (PT). Most frequent clinical manifestations are subcutaneous emphysema, pneumomediastinum and unilateral or bilateral pneumothorax, even if occasionally ITI can occur without significant symptoms. Diagnosis mainly relies on clinical suspicion and CT scan, although flexible bronchoscopy remains the gold standard, allowing to identify location and size of the injury. EI and PT related ITIs more commonly consist of longitudinal tear involving the pars membranacea. Based on the depth of tracheal wall injury, Cardillo and colleagues proposed a morphologic classification of ITIs, attempting to standardize their management. Nevertheless, in literature there are no unambiguous guidelines on the best therapeutic modality: management and its timing remain controversial. Historically, surgical repair was considered the gold standard, mainly in high-grade lesions (IIIa-IIIb), carrying high morbi-mortality rates, but currently the development of promising endoscopic techniques through rigid bronchoscopy and stenting could allow for bridge treatment, delaying surgical approach after improving general conditions of the patient, or even for definitive repair, ensuring lower morbi-mortality rates especially in high-risk surgical candidates. Our perspective review will cover all the above issues, aiming at providing an updated and clear diagnostic-therapeutic pathway protocol, which could be applied in case of unexpected ITI.

The Role of Surgery in Patients with COVID-19-Related Thoracic Complications.

Objective: Patients with several thoracic complications induced by SARS-CoV-2 infection may benefit from surgery, but its role in this condition is largely unknown, and many surgeons' advice against any surgical referrals. Our aim is to investigate the efficacy and safety of surgery in COVID-19 patients with thoracic complications requiring surgery. Methods: We designed a multicenter observational study, involving nine thoracic surgery departments, evaluating patients who developed thoracic complications in hospital, surgically managed from March 1, 2020, to May 31, 2021. An overall 30-day mortality was obtained by using the Kaplan-Meier method. Multivariable Cox regression model and logistic models were applied to identify the variables associated with mortality and postoperative complications. Results: Among 83 patients, 33 (40%) underwent surgery for complicated pneumothorax, 17 (20.5%) for pleural empyema, 13 (15.5%) for hemothorax, 8 (9.5%) for hemoptysis, 5 patients (6%) for lung abscess, 4 (5%) for infected pneumatoceles, and 3 (3.5%) for other causes. Within 30 days of surgery, 60 patients (72%) survived. At multivariable analysis, age (HR 1.05 [95% CI, 1.01, 1.09], p = 0.022), pulmonary hypertension (HR 3.98 [95% CI, 1.09, 14.5], p = 0.036), renal failure (HR 2.91 [95% CI, 1.19, 7.10], p-value 0.019), thoracotomy (HR 4.90 [95% CI, 1.84, 13.1], p-value 0.001) and infective affections (HR 0.17 [95% CI, 0.05, 0.58], p-value 0.004) were found to be independent prognostic risk factors for 30-day mortality. Age (OR 1.05 [95% CI, 1.01, 1.10], p = 0.023) and thoracotomy (OR 3.85 [95% CI, 1.35, 12.0] p = 0.014) became significant predictors for 30-day morbidity. Conclusion: Surgical management of COVID-19-related thoracic complications is affected by high mortality and morbidity rates, but a 72% survival rate still seems to be satisfactory with a rescue intent. Younger patients without pulmonary hypertension, without renal insufficiency and undergoing surgery for infectious complications appear to have a better prognosis.

Standardization of Procedures to Contain Cost and Reduce Variability of Care After the Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has changed many aspects of our private and professional routine. In particular, the lockdowns have severely affected the entire healthcare system and hospital activities, forcing it to rethink the protocols in force. We suggest that this scenario, in spite of the new challenges involving so far complex healthcare providers, may lead to the unique opportunity to rethink pathways and management of patients. Indeed, having to resume institutional activity after a long interruption that has completely canceled the previously existing schemes, healthcare providers have the unique opportunity to overcome obsolete and "we have always done in this way" model on the wave of the general desire to resume a normal life. Furthermore, the pandemic has highlighted some flaws in our health system, highlighting those critical issues that most need to be addressed. This article is a review of pre-pandemic literature addressing the use of Lean Six Sigma (LSS) and standardization processes in thoracic surgery to improve efficiency. Our goal is to identify the main issues that could be successfully improved along the entire pathway of a patient from the first referral to diagnosis, hospitalization, and surgical operation up to convalescence. Furthermore, we aim to identify the standardization processes that have been implemented to achieve significant improvements in patient outcomes while reducing costs. The methods and goals that could be used in the near future to modernize our healthcare systems are drawn up from a careful reading and interpretation in light of the pandemic of the most significant review articles in the literature.

Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant: An Italian Multicenter Experience.

Background and aim: Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers. Methods: All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR. Results: Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9-306) since LT and PMR was performed after 2.4 months (0-43.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50-365); median post-operative overall stay 5 days (2-11). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7-213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12-74), respectively, with a median OS of 51 months (95%CI 24-78). Conclusion: Selected patients with isolated pulmonary HCC-recurrence after LT and with preserved hepatic function showed that a pulmonary metastasectomy could be efficacious in managing a PM-HCC and could give an opportunity for long-term survival.

Lung transplantation from donation after controlled cardiocirculatory death. Systematic review and meta-analysis.

BACKGROUND: The interest in donation after cardiocirculatory death (DCD) donors for lung transplantation (LT) has been recently rekindled due to lung allograft shortage. Clinical outcomes following DCD have proved satisfactory. The aim of this systematic review is to provide a thorough analysis of published experience regarding outcomes of LT after controlled DCD compared with donation after brain death (DBD) donors. METHODS: We performed a literature search in Cochrane Database of Systematic Reviews, PubMed and Web of Science using the items "lung transplantation" AND "donation after circulatory death" on November 1, 2018. The full text of relevant articles was evaluated by two authors independently. Quality assessment was performed using the NIH protocol for case-control and case series studies. A pooled Odds ratio (OR) and mean differences with inverse variance weighting using DerSimonian-Laird random effect models were computed to account for between-trial variance (τ2). RESULTS: Of the 508 articles identified with our search, 9 regarding controlled donation after cardiac death (cDCD) were included in the systematic review, including 2973 patients (403 who received graft from DCD and 2570 who had DBD). Both 1-year survival and 2 and 3-grade primary graft dysfunction (PGD) were balanced between the two cohorts (OR = 1.00 and 1.03 respectively); OR for airway complications was 2.07 against cDCD. We also report an OR = 0.57 for chronic lung allograft dysfunction (CLAD) and an OR = 0.57 for 5-year survival against cDCD. CONCLUSIONS: Our meta-analysis shows no significant difference between recipients after cDCD or DBD regarding 1-year survival, PGD and 1-year freedom from CLAD. Airway complications and long-term survival were both related with transplantation after cDCD, but these statistical associations need further research.

Pulmonary metastasectomy: an overview.

Metastasectomy is the most frequent surgical resection undertaken by thoracic surgeons, being the lung the second common site of metastases. The present oncological criteria for pulmonary metastasectomy are: (I) the primary cancer need to be controlled or controllable; (II) no extrathoracic metastasis-that is not controlled or controllable-exists; (III) all of the tumor must be resectable, with adequate pulmonary reserve; (IV) there are no alternative medical treatment options with lower morbidity. General favourable prognostic features in patients with pulmonary metastases are: (I) one or few metastases; (II) long disease free interval; (III) normal CEA levels in colorectal cancers. Negative predictive features in patients candidate to pulmonary metastasectomies are: (I) active primary cancer; (II) extrathoracic metastases; (III) inability to obtain surgical radicality; (IV) mediastinal lymphatic spread. The lack of controlled trials and studies limited by short follow-up and small cohorts did not allow to overcome some skepticism; moreover, the heterogeneity of these patients in terms of demographic, biologic and histologic characteristics represents a clear limit even in the largest series. On the basis of present knowledge, without results coming from on-going randomized trials, radical resection, histology, and disease free interval seem to be independent prognostic factors identifying a cohort of patients maximally benefitting from lung metastasectomy.

Plasmatic extracellular vesicle microRNAs in malignant pleural mesothelioma and asbestos-exposed subjects suggest a 2-miRNA signature as potential biomarker of disease.

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an aggressive cancer mainly caused by asbestos exposure and refractory to current therapies. Specific diagnostic markers for early MPM diagnosis are needed. Changes in miRNA expression have been implicated in several diseases and cancers, including MPM. We examined if a specific miRNA signature in plasmatic extracellular vesicles (EV) may help to discriminate between malignant pleural mesothelioma patients (MPM) and subjects with Past Asbestos Exposure (PAE). METHODOLOGY/PRINCIPAL FINDINGS: We investigated 23 MPM patients and 19 cancer-free subjects with past asbestos exposure (PAE). We screened 754 miRNAs in plasmatic EVs by OpenArray and found 55 differential miRNAs using logistic regression models adjusted for age, sex, BMI, and smoking. Among the top-20 differential miRNAs chosen for validation by Real time PCR, 16 were confirmed. Using receiver operating characteristic (ROC) curve analysis, the most discriminating miRNA combination was given by miR-103a-3p + miR-30e-3p, which generated an AUC of 0.942 (95% CI 0.87-1.00), with a sensitivity of 95.5% and a specificity of 80.0%. Using multivariate Cox regression analysis including gender, age, BMI and smoking we found a Hazard Ratio for miR-103a-3p above the median of 0.37 (95%CI 0.13-1.13) and of 0.51 (95%CI 0.17-1.52) for miR-30e-3p. CONCLUSIONS: This study suggests EV-associated miR-103a-3p and miR-30e-3p are able to discriminate MPM from PAE subjects. Larger and prospective studies are needed to confirm these two-miRNA signature alone or in combination with other biomarkers as diagnostic tools for MPM.