Role of systemic immunosuppression on subglottic stenosis in granulomatosis with polyangiitis: Analysis of a single-centre cohort.

PURPOSE: Subglottic stenosis (SGS) is a potentially life-threatening manifestation of granulomatosis with polyangiitis (GPA). Endoscopic dilation is effective, but relapses are frequent and the benefit of systemic immunosuppression in this setting is still controversial. We aimed to investigate the role of immunosuppressive treatment on SGS relapse risk. METHODS: This is a retrospective observational study based on review of medical charts among our cohort of patients with GPA. RESULTS: Twenty-one patients with SGS-GPA were identified, with a prevalence of 20% among our entire GPA cohort (n = 105). Compared to patients without SGS, patients with SGS-GPA had an earlier disease onset (mean age 30.2 vs. 47.3 years, p<0.001), and lower BVAS (mean 10.5 vs 13.5; p = 0.018). Five patients didn't receive systemic immunosuppression for SGS and they all (100%) relapsed after the first procedure, while among medical treatment group relapse rate was 44% (p = 0.045). When single treatment regimens are considered, rituximab (RTX) and cyclophosphamide (CYC) yielded a protective role towards the need of subsequent dilation procedure after the first if compared with absence of medical treatment. Patients with SGS and generalized disease, who initially received either a RTX- or a CYC-based induction treatment, and higher cumulative doses of glucocorticoids, showed a delayed median time to SGS relapse (36 vs. 12 months, p = 0.024). CONCLUSIONS: Subglottic stenosis is highly prevalent in patients with GPA and may define a milder systemic disease subset occurring more frequently in younger patients. Systemic immunosuppression provides benefit in preventing recurrence of SGS in GPA patients and regimens based on cyclophosphamide or rituximab might have a non-redundant role in this setting.

Chest Drainage Therapy: What Comes out of Pandora's Box Can Affect Patient Outcomes.

Background: Over the last 100 years, the original three-bottle chest drainage system has been variously engineered into compact disposables and electronic units. Clinicians are now surrounded by a plethora of different types of systems, but little is known about the way that they work and perform. Thus, we sought to test the performance of the most commonly used chest drainage units under conditions that are relevant to clinical practice. Methods: A pleural space environment simulator was built. Thirty-two units were tested under four clinical scenarios: air leak interpretation during quiet breathing and after obstructed inspiration (−5 to −150 cmH2O), a buildup of negative pressure (−100 cmH2O), a bronchopleural fistula (10 L/min) and the need for effective external suction in the presence of air leakage. Twenty-five units were "traditional" thoracic drainages, five were "digital" low-flow/low-vacuum pumps and two were hybrids (a combination of the two). According to the design of the seal and of the suction control, the units were classified as wet-wet, wet-dry and dry-dry. Results: All wet units showed reverse air flow, with the potential to mimic an air leak when there was none. Ten wet units showed no automatic negative pressure relief features, while five dry-dry did but were slow to react. Ten wet and five dry-dry units showed no capability to handle a 10 L/min leak, as they were restrictive to flow (peak pressure up to 55 cmH2O). Only seven dry-suction units were able to maintain the set suction at high airflow rates (>20 L/min). Conclusions: Different chest drainage unit designs lead to different performances, some of which may negatively impact patient outcomes. This sounds the call to tailor our clinical practice for the individual patient. A paradigm shift to better understand all components of pleural physiology post-surgical intervention on this relatively neglected topic is needed to improve our daily practice.

The procedure and effectiveness of release maneuvers in tracheobronchial resection and reconstruction.

Background: Surgical resection and reconstruction are effective and radical treatments for tracheal tumors. Tension-free, well-perfused anastomosis plays a crucial role in postoperative prognosis. The use of various release maneuvers may be required to minimize anastomotic tension. However, the detailed procedures and effectiveness of them are seldomly reported. In the current study, we demonstrated the procedures and advantages of various release maneuvers during tracheal resection and reconstruction. Methods: All patients who underwent tracheobronchial resection and reconstruction between January 2019 to December 2021 were included in the study. The patients underwent tracheal release maneuvers, including laryngeal suprahyoid, pericardial, hilar, and inferior pulmonary ligament releasing. The patients' clinical features, surgical procedures, complications and postoperative outcomes were also described. Results: A total of 67 patients received release maneuvers during tracheobronchial surgery. Males accounted for a greater proportion (46/67, 65.7%) of the cohort. The mean age was 44.4 years. Most lesions were located in the thoracic and cervical trachea (21/67 and 17/67, respectively), and 18 cases of carinal (9/67) and bronchial (9/67) lesions were also included. Inferior pulmonary ligament releasing was applied to most noncervical lesion patients (39/67). Two cases of thyroid carcinoma with tracheal invasion received laryngeal suprahyoid release maneuvers. Adenoid cystic carcinoma (26.9%) and squamous cell carcinoma (14.9%) were the most commonly seen malignancies. Postoperative bronchoscopy showed no anastomotic abnormalities, including ischemic change, necrosis, or dehiscence. The median postoperative hospital stay was 7 days, ranging from 4 to 38 days. In the current study, a patient with postoperative aspiration had the longest hospital stay. In addition, 3 cases of anastomotic stenosis and laryngeal edema were observed. No other maneuver-related complications or particular discomforts were reported during the 6-month follow-up. Conclusions: Anastomosis is the key to successful tracheobronchial resection and reconstruction. Release maneuvers are recommended to facilitate tension-free anastomosis. In addition to simple neck flexion and paratracheal dissection, laryngeal, hilar, and pericardial releasing allow longer trachea to be resected and preservation of well-vascularized anastomosis. The release maneuvers showed acceptable effect and reliable safety without significant morbidity or mortality.

Catamenial Pneumothorax as the First Expression of Thoracic Endometriosis Syndrome and Pelvic Endometriosis.

OBJECTIVE: The menstrual-related catamenial pneumothorax (CP) can be the first expression of thoracic endometriosis syndrome (TES), which is the presence of endometriotic lesions in the lungs and pleura, and pelvic endometriosis (PE). This study aims to analyze our experience with this specific correlation describing our multidisciplinary approach to CP. METHODS: Hospital records of 32 women, operated for CP at our Department from January 2001 to December 2021 were reviewed. Surgical treatment consisted of videothoracoscopy and laparoscopy when indicated. RESULTS: TES and PE were diagnosed in 13 (40.6%) and 12 (37.5%) women, respectively. The association of TES and PE was present in 11 cases (34%). Fifteen patients (46.9%) underwent laparoscopy, of which 11 concurrently with videothoracoscopy. Most of the patients affected had stage III-IV endometriosis (40.6%). All patients received hormonal therapy after surgery. Five patients with PE conceived spontaneously resulting in six live births. The mean follow-up was 117 ± 71 months (range 8-244). Pneumothorax recurrence occurred in six patients (18.8%). At present, all women are asymptomatic, with no sign of pneumothorax recurrence. CONCLUSIONS: CP might be the first expression of TES and/or PE. A multidisciplinary approach is advocated for optimal management of the disease.

Venoarterial Extracorporeal Membrane Oxygenation Support in Lung Cancer Resection.

Cardiovascular comorbidities often prevent patients with otherwise resectable early-stage lung cancer from undergoing surgery due to prohibitive perioperative risk. Here we describe the intraoperative use of venoarterial (VA) extracorporeal membrane oxygenation in a stage cIIA lung cancer patient with arterial infiltration and severe postischemic dilated cardiomyopathy (ejection fraction, 0.23) undergoing left upper lobectomy with pulmonary artery angioplasty. Providing intraoperative cardiovascular and respiratory function support, venoarterial extracorporeal membrane oxygenation represents a suitable option for patients with heart failure, ensuring an adequate hemodynamic profile and reducing the risk of complications. Thus, these otherwise inoperable patients can be offered a potentially curative surgical resection of the malignancy.

Treatment of Thoracic Endometriosis Syndrome: A Meta-Analysis and Review.

BACKGROUND: Thoracic endometriosis syndrome (TES) is a rare disorder characterized by the presence of functional endometrial tissue within the chest cavity. Up to 80% of women with TES present with concomitant pelvic endometriosis. The diagnostic-curative path is defined by both thoracic surgeons and gynecologists, consistent with the manifestation of the disease. The aim of the study was to analyze the different approaches to generate an ideal diagnosis-treatment algorithm that can be shared by both specialties. METHODS: We searched PubMed and Scopus for studies that were completed by March 2019 and that included at least 8 patients with TES. Information on preoperative exams, surgical technique, postoperative management, and recurrence of disease was collected for meta-analysis. RESULTS: Twenty-five studies including a total of 732 patients were eligible. Almost all of the patients underwent radiologic pelvis investigation (96%; confidence interval [CI], 87%-100%). Videothoracoscopy was the preferred surgical technique (84%; 95% CI, 66%-96%). Intraoperative evaluation revealed the presence of diaphragmatic anomalies in 84% of cases (95% CI, 73%-93%). The overall pooled prevalence of concomitant or staged laparoscopy was 52% (95% CI, 18%-85%). Postoperative hormone therapy was heterogeneous with a pooled prevalence of 61% (95% CI, 33%-86%; I2 = 95.6%; P < .01). Recurrence of symptoms was documented in 27% of patients (95% CI, 20%-34%; I2 = 54.7%; P < .01). CONCLUSIONS: TES should be managed jointly by thoracic surgeons and gynecologists. Chest-abdomen magnetic resonance imaging seems to offer the most details for TES. Combined or staged videothoracoscopy and laparoscopy can provide adequate information to fine-tune proper surgical treatment and postoperative medical therapy.

Perspective: Did Covid-19 Change Non-small Cell Lung Cancer Surgery Approach?

The novel coronavirus (Covid-19), as of January 2021, infected more than 85 million people worldwide, causing the death of about 1,840 million. Italy had more than 2 million infected and about 75,000 deaths. Many hospitals reduced their ordinary activity by up to 80%, to leave healthcare staff, wards, and intensive care unit (ICU) beds available for the significant number of Covid-19 patients. All this resulted in a prolonged wait for hospitalization of all other patients, including those with non-small cell lung cancer (NSCLC) eligible for surgery. The majority of thoracic surgery departments changed the clinical-therapeutic path of patients, re-adapting procedures based on the needs dictated by the pandemic while not delaying the necessary treatment. The establishment of Covid-19-free hub centers allowed some elective surgery in NSCLC patients but most of the operations were delayed. The technology has partly facilitated patients' visits through telemedicine when security protocols have prevented face-to-face assessments. Multidisciplinary consultations had to deal also with the priority of the NSCLC cases discussed. Interpretation of radiologic exams had to take into account the differential diagnosis with Covid-19 infection. All the knowledge and experience of the past months reveal that the Covid-19 pandemic has not substantially changed the indications and type of surgical treatment in NSCLC. However, the diagnostic process has become more complex, requiring rigorous planning, thus changing the approach with the patients.

CXCR4 engagement triggers CD47 internalization and antitumor immunization in a mouse model of mesothelioma.

Boosting antitumor immunity has emerged as a powerful strategy in cancer treatment. While releasing T-cell brakes has received most attention, tumor recognition by T cells is a pre-requisite. Radiotherapy and certain cytotoxic drugs induce the release of damage-associated molecular patterns, which promote tumor antigen cross-presentation and T-cell priming. Antibodies against the "do not eat me" signal CD47 cause macrophage phagocytosis of live tumor cells and drive the emergence of antitumor T cells. Here we show that CXCR4 activation, so far associated only with tumor progression and metastasis, also flags tumor cells to immune recognition. Both CXCL12, the natural CXCR4 ligand, and BoxA, a fragment of HMGB1, promote the release of DAMPs and the internalization of CD47, leading to protective antitumor immunity. We designate as Immunogenic Surrender the process by which CXCR4 turns in tumor cells to macrophages, thereby subjecting a rapidly growing tissue to immunological scrutiny. Importantly, while CXCL12 promotes tumor cell proliferation, BoxA reduces it, and might be exploited for the treatment of malignant mesothelioma and a variety of other tumors.

Derivation and validation of a nomogram model for pulmonary thromboembolism in patients undergoing lung cancer surgery.

BACKGROUND: A specific risk-stratification tool is needed to facilitate safe and cost-effective approaches to the prophylaxis of acute pulmonary thromboembolism (PTE) in lung cancer surgery patients. This study aimed to develop and validate a simple nomogram model for the prediction of PTE after lung cancer surgery using readily obtainable clinical characteristics. METHODS: A total of 14,427 consecutive adult patients who underwent lung cancer surgery between January 2015 and July 2018 in our institution were retrospectively reviewed. Included in the cohort were 136 patients who developed PTE and 544 non-PTE patients. The patients were randomly divided into the derivation group (70%, 95 PTE patients and 380 non-PTE patients) and the validation group (30%, 41 PTE patients and 164 non-PTE patients). A nomogram model was developed based on the results of multivariate logistic analysis in the derivation group. The cut-off values were defined using Youden's index. The prognostic accuracy was measured by area under the curve (AUC) values. RESULTS: In the derivation group, multivariate logistic analysis was carried out to evaluate the risk score. The risk assessment model contained five variables: age [95% confidence interval (CI): 1.008-1.083, P=0.016], body mass index (95% CI: 1.077-1.319, P=0.001), operation time (95% CI: 1.002-1.014, P=0.008), the serum level of cancer antigen 15-3 (CA15-3) before surgery (95% CI: 1.019-1.111, P=0.005), and the abnormal results of compression venous ultrasonography before surgery (95% CI: 2.819-18.838, P<0.001). All of them were independent risk factors of PTE. To simplify the risk assessment model, a nomogram model was established, which showed a good predictive performance in the derivation group (AUC 0.792, 95% CI: 0.734-0.853) and in the validation group (AUC 0.813, 95% CI: 0.737-0.890). CONCLUSIONS: A high-performance nomogram was established on the risk factors for PTE in patients undergoing lung cancer surgery. The nomogram could be used to provide an individual risk assessment and guide prophylaxis decisions for patients. Further external validation of the model is needed in lung cancer surgery patients in other clinical centers.

A risk stratification scheme for synchronous oligometastatic non-small cell lung cancer developed by a multicentre analysis.

BACKGROUNDS: Oligometastatic Non-Small Cell Lung Cancer (NSCLC) patients represent a category without a standard therapeutic approach. However, in selected oligometastatic NSCLC, radical surgery seems to offer a good prognosis. This retrospective study aimed to analyse the long-term outcomes of synchronous oligometastatic patients treated with curative intent and identify the factors associated with better results and the proposal of a risk stratification system for classifying the synchronous oligometastatic NSCLC. METHODS: The medical records of patients from 18 centres with pathologically diagnosed synchronous oligometastatic NSCLC were retrospectively reviewed. The inclusion criteria were synchronous oligometastatic NSCLC, radical surgical treatment of the primary tumour with or without neoadjuvant/adjuvant therapy and radical treatment of all metastatic sites. The Kaplan - Meier method estimated survivals. A stratified backward stepwise Cox regression model was assessed for multivariable survival analyses. RESULTS: 281 patients were included. The most common site of metastasis was the brain, in 50.89 % patients. Median overall survival was 40 months (95 % CI: 29-53). Age ≤65 years (HR = 1.02, 95 % CI: 1.00-1.05; p = 0.019), single metastasis (HR = 0.71, 95 % CI: 0.45-1.13; p = 0.15) and presence of contralateral lung metastases (HR = 0.30, 95 % CI: 0.15 - 0.62; p = 0.001) were associated with a good prognosis. The presence of pathological N2 metastases negatively affected survival (HR = 2.00, 95 % CI: 1.21-3.32; p = 0.0065). These prognostic factors were used to build a simple risk classification scheme. CONCLUSIONS: Treatment of selected synchronous oligometastatic NSCLC with curative purpose could be conducted safely and at acceptable 5-year survival levels, especially in younger patients with pN0 disease.

Correlation of Computed Tomography Parameters with Histology, Stage and Prognosis in Surgically Treated Thymomas.

Background and objectives: The histological classification and staging of thymic tumors remains a matter of debate. The correlation of computed tomography (CT) parameters with tumor histology and stage also still has to be completely assessed. The aim of this study was therefore to analyze the correlation of radiological parameters with histological and staging classifications of thymomas evaluating their prognostic role. Methods: Data of 50 patients with thymoma submitted to a complete surgical treatment between 2005 and 2015 were retrospectively analyzed. Tumors were classified according to the WHO and Suster and Moran (S&M) histological classifications and to the Masaoka-Koga and tumor, node and metastases (TNM) staging systems. The correlation of CT features with histology and stage and the prognostic role of histopathological and radiological features were assessed. Results: Five-year overall (OS) and disease-free survival (DFS) were 90.3% and 81.1%, respectively. A significant correlation of DFS with the Masaoka-Koga (p = 0.001) and TNM staging systems (p = 0.002) and with the S&M (p = 0.02) and WHO histological classifications (p = 0.04) was observed. CT scan features correlated with tumor stage, histology and prognosis. Moderately differentiated tumors (WHO B3) had a significantly higher incidence of irregular shape and contours (p = 0.002 and p = 0.001, respectively) and pericardial contact (p = 0.036). A larger tumor volume (p = 0.03) and a greater length of pleural contact (p = 0.04) adversely influenced DFS. The presence of pleural (p < 0.001) or lung invasion (p = 0.02) and of pleural effusion (p = 0.004) was associated with a significantly worse OS. Conclusions: Pre-operative CT scan parameters correlate with stage and histology, and have a prognostic role in surgically treated thymomas.

Prognostic role of positron emission tomography and computed tomography parameters in stage I lung adenocarcinoma.

Background According to the current pathological classification, lung adenocarcinoma includes histological subtypes with significantly different prognoses, which may require specific surgical approaches. The aim of the study was to assess the role of CT and PET parameters in stratifying patients with stage I adenocarcinoma according to prognosis. Patients and methods Fifty-eight patients with pathological stage I lung adenocarcinoma who underwent surgical treatment were retrospectively reviewed. Adenocarcinoma in situ and minimally-invasive adenocarcinoma were grouped as non-invasive adenocarcinoma. Other histotypes were referred as invasive adenocarcinoma. CT scan assessed parameters were: ground glass opacity (GGO) ratio, tumour disappearance rate (TDR) and consolidation diameter. The prognostic role of the following PET parameters was also assessed: standardized uptake value (SUV) max, SUVindex (SUVmax to liver SUVratio), metabolic tumour volume (MTV), total lesion glycolysis (TLG). Results Seven patients had a non-invasive adenocarcinoma and 51 an invasive adenocarcinoma. Five-year disease-free survival (DFS) and cancer-specific survival (CSS) for non-invasive and invasive adenocarcinoma were 100% and 100%, 70% and 91%, respectively. Univariate analysis showed a significant difference in SUVmax, SUVindex, GGO ratio and TDR ratio values between non-invasive and invasive adenocarcinoma groups. Optimal SUVmax, SUVindex, GGO ratio and TDR cut-off ratios to predict invasive tumours were 2.6, 0.9, 40% and 56%, respectively. TLG, SUVmax, SUVindex significantly correlated with cancer specific survival. Conclusions CT and PET scan parameters may differentiate between non-invasive and invasive stage I adenocarcinomas. If these data are confirmed in larger series, surgical strategy may be selected on the basis of preoperative imaging.

Therapeutic strategy for tracheal chondrosarcoma: report of two cases.

Primary chondrosarcoma of the trachea is an extremely rare tumor. We report two cases of tracheal chondrosarcoma describing the role of surgical and conservative treatment. Endoscopic treatment with rigid bronchoscopy was performed in both patients to restore airway patency and obtain histological specimens for diagnosis. One of the patients subsequently underwent successful tracheal resection and reconstruction. The other patient, who had a contraindication to surgical treatment due to associated diseases underwent iterative endoscopic LASER treatment and is alive three years after the first diagnosis. Surgical treatment remains the treatment of choice of tracheal chondrosarcoma. When surgery is contraindicated endoscopic treatment may allow relatively longterm survival due to the slow growth of these tumors.

Cost-effectiveness of endoscopic mediastinal staging.

Lung cancer is the first cause of cancer-related mortality. Mediastinal staging has a main role in the definition of the therapeutic strategy in early-stage and locally-advanced non-small cell lung cancer (NSCLC). Non-invasive mediastinal staging with CT or PET imaging has relatively limited accuracy, and nodal biopsy may be required to reach adequate staging results. In the last two decades endoscopic techniques have been increasingly used in the field of mediastinal staging thanks to a reduced invasiveness and to the possibility of obtaining a more thorough assessment in comparison with surgical techniques. However, the ideal staging strategy is still a matter for debate, particularly considering the cost-effectiveness of the different approaches. Complication-rate, costs, impact on quality of life, time delay to treatment and survival of the different staging techniques still have to be analyzed in detail. Other issues to be discussed are the optimal combination of staging approaches and the influence of factors as the prevalence of nodal disease on the cost-effectiveness of the different methods. Future issues of invasive staging concern the possibility of extending the definition of nodal status to N1 intrapulmonary nodes, in the light of the development of new oncological and surgical therapeutic approaches.

Surgical treatment of single and multiple thymoma recurrences.

OBJECTIVES: A significant number of patients with thymoma develop a recurrence after surgery. The results of previous studies analyzing therapeutic strategies in the treatment of recurrences have been controversial. Aim of the study was to evaluate the role of surgery in the treatment of thymoma recurrences assessing prognostic factors related with survival. METHODS: Between January 1993 and September 2018, 27 of 161 patients had a recurrence after complete thymoma resection. Twenty-one (13%) underwent surgical treatment of the recurrence. Primary tumor stage was: I in a patient, IIa in five, IIb in nine and III in six. The recurrence was regional in all patients and both regional and distant in four. WHO histological classification was: A in two patients, B1 in two, B2 in seven and B3 in 10 patients. RESULTS: Median disease-free survival from surgical treatment of the primary tumor and recurrence was 44 months (1-124). Thirty-eight operations were performed (range 1-5). Complete resection rate was 66%. Adjuvant radiotherapy and chemotherapy after surgical treatment of recurrences were performed respectively in ten and nine patients, including eight patients with multiple recurrences. Five and 10-year tumor-specific survival from recurrence was, respectively, 79% and 66%. Survival analysis showed a significant correlation between survival and WHO classification, with a significantly lower survival in patients with B3 tumors in comparison with A to B2 tumors (p = 0.026). CONCLUSIONS: Long-term survival was observed following surgical treatment of thymoma recurrences. These results were observed even after multiple recurrences when surgical treatment was performed within a multimodality oncological approach.