Advances in Endoscopic Management of Endobronchial Carcinoid.

INTRODUCTION: Bronchial carcinoid (BC) tumors represent between 1% and 5% of all lung cancers and about 20-30% of carcinoid tumors; they are classified into two groups: typical and atypical bronchial carcinoids. The aim of the present study was to review the results of endoscopic treatments as an alternative to surgical treatment in selected patients. MATERIALS AND METHODS: The present study was a retrospective and multicentric study, in which all data were reviewed for patients with BC in the central airways, referred to the Thoracic Surgery Units of Luigi Vanvitelli University of Naples and Sant'Andrea Hospital in Rome between October 2012 and December 2022 Overall, 35 patients, 13 of whom were female, were included in the study (median age, 53 years; range, 29-75 years). All patients underwent rigid bronchoscopy combined with flexible bronchoscopy. Tumor clearance was mostly performed by use of Argon Plasma Coagulation or Thulep Laser, mechanical debridement and excision with the use of forceps and aspirator through the working channel of the 8.5 mm-sized rigid bronchoscope. There were no complications during the treatment. RESULTS: Endobronchial treatment provided complete tumor eradication in all patients; two patients had controlled bleeding complications; however, bleeding was well controlled without patient desaturation, and only one patient died of renal failure during the follow-up period. We found two recurrences in the left and right main bronchus, in patients with atypical carcinoma during fiberoptic bronchoscopy follow-up. Only one patient died of renal failure. At the first analysis, there were no significant differences between the patients receiving endobronchial treatment and patients receiving surgical treatment in the present study (p-value > 0.05-it means statistically insignificant). CONCLUSIONS: Endobronchial treatment is a valid and effective alternative for patients with BC unsuitable for surgery.

Surgical Resection of Pulmonary Metastases from Melanoma in Oligometastatic Patients: Results from a Multicentric Study in the Era of Immunoncology and Targeted Therapy.

In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies has revolutionized the treatment of patients with advanced stage III and stage IV melanoma. Even though lungs represent the most frequent site of melanoma metastases, only limited data are available on the role of surgery in isolated pulmonary metastases from malignant melanoma (PmMM) in the era of ESTs. The aim of this study is to describe the outcomes of patients who underwent metastasectomy of PmMM in the era of ESTs, in order to identify prognostic factors affecting survival and to provide a framework for more informed patient selection of treatmeant with lung surgery in the future. Clinical data of 183 patients who underwent metastasectomy of PmMM between June 2008 and June 2021 were collected among four Italian Thoracic Centers. The main clinical, surgical and oncological variables reviewed were: sex, comorbidities, previous oncological history, melanoma histotypes and primary site, date of primary cancer surgical treatment, melanoma growth phase, Breslow thickness, mutation pattern disease, stage at diagnosis, metastatic sites, DFI (Disease Free Interval), characteristics of lung metastases (number, side, dimension, type of resection), adjuvant therapy after lung metastasectomy, site of recurrence, disease-free survival (DFS) and cancer-specific survival (CSS; defined as the time interval between the first melanoma resection or lung metastasectomy and death from cancer). All patients underwent surgical resection of the primary melanoma before lung metastasectomy. Twenty-six (14.2%) patients already had a synchronous lung metastasis at the time of primary melanoma diagnosis. A wedge resection was performed in 95.6% of cases to radically remove the pulmonary localizations, while an anatomical resection was necessary in the remaining cases. The incidence of major post-operative complications was null, while only 21 patients (11.5%) developed minor complications (mainly air leakage followed by atrial fibrillation). The mean in-hospital stay was 4.46 ± 2.8 days. Thirty- and sixty-day mortality were null. After lung surgery, 89.6% of the population underwent adjuvant treatments (47.0% immunotherapy, 42.6% targeted therapy). During a mean FUP of 107.2 ± 82.3 months, 69 (37.7%) patients died from melanoma disease, 11 (6.0%) from other causes. Seventy-three patients (39.9%) developed a recurrence of disease. Twenty-four (13.1%) patients developed extrapulmonary metastases after pulmonary metastasectomy. The CSS from melanoma resection was: 85% at 5 years, 71% at 10 years, 54% at 15 years, 42% at 20 years and 2% at 25 years. The 5- and 10-year CSS from lung metastasectomy were 71% and 26%, respectively. Prognostic factors negatively affecting CSS from lung metastasectomy at multivariable analysis were: melanoma vertical growth (p = 0.018), previous metastatic sites other than lung (p < 0.001) and DFI < 24 months (p = 0.007). Our results support the evidence that surgical indication confirms its important role in stage IV melanoma with resectable pulmonary metastases, and selected patients can still benefit from pulmonary metastasectomy in terms of overall cancer specific survival. Furthermore, the novel systemic therapies may contribute to prolonged survival after systemic recurrence following pulmonary metastasectomy. Patients with long DFI, radial growth melanoma phase and no site of metastatization other than lung seem to be the best candidate cases for lung metastasectomy; however, to drive stronger conclusions, further studies evaluating the role of metastasectomy in patients with iPmMM are needed.

Bilateral Ultrasound-Guided Erector Spinae Plane Block for Pectus Excavatum Surgery: A Retrospective Propensity-Score Study.

OBJECTIVE: Pectus excavatum (PE) repair is burdened by severe postoperative pain. This retrospective study aimed to determine whether the analgesic effect of ultrasound-guided erector spinae plane block (ESPB) plus standard intravenous analgesia (SIVA) might be superior to SIVA alone in pain control after PE surgical repair via Ravitch or Nuss technique. DESIGN: A retrospective cohort study. SETTING: At a university hospital. PARTICIPANTS: All participants were scheduled for surgical repair of PE. INTERVENTIONS: From January 2017 to December 2019, all patients who received ESPB plus SIVA or SIVA alone were investigated retrospectively. A 2:1 propensity-score matching analysis considering preoperative variables was used to compare analgesia efficacy in 2 groups. All patients received a 24-hour continuous infusion of tramadol, 0.1 mg/kg/h, and ketorolac, 0.05 mg/kg/h, via elastomeric pump, and morphine, 2 mg, intravenously as a rescue drug. The ESPB group received preoperative bilateral ESPB block. Postoperative pain, reported using a numerical rating scale at 1, 12, 24, and 48 hours after surgery; the number of required rescue doses; total postoperative morphine milligram equivalents consumption; and the incidence of postoperative nausea and vomit were analyzed. MEASUREMENT AND MAIN RESULTS: A total of 105 patients were identified for analysis. Propensity-score matching resulted in 38 patients in the SIVA group and 19 patients in the ESPB group. Postoperative pain, the number of rescue doses, and postoperative nausea and vomit incidences were lower in the ESPB group (p < 0.005). CONCLUSIONS: Erector spinae plane block may be an effective option for pain management after surgical repair of PE as part of a multimodal approach. This study showed good perioperative analgesia, opioid sparing, and reduced opioid-related adverse effects.

Histological growth patterns and molecular analysis of resected colorectal lung metastases.

Lung is the site of metastasis in about 15-25 % of colorectal cancer (CRC) patients. Lung metastasectomy of CRC represents a standard therapy in patients with resectable metastases. In this study we investigated both histological patterns of metastases and mutations in MAPkinase pathway genes and their relationship to prognosis. The study included 74 patients that underwent metastasectomy of colorectal lung metastasis (CLM). In patients that underwent surgical resection of more than one metastasis in the same operation the largest was chosen. In patients that had undergone multiple lung metastasectomy only the sample from the first metastasectomy was included. Histologically metastases were scored according to amount and distribution of necrosis and fibrosis and three patterns were identified: "pattern A", metastasis with extensive, confluent central necrosis surrounded by a rim of neoplastic glands; "pattern B", metastasis characterized by a proliferation of neoplastic glands in a dense stroma with focal necrosis mainly intraglandular; "pattern C", metastasis with a mixed A and B morphology. In all samples direct sequencing of exon 2 of KRAS and NRAS genes and exon 15 of BRAF genes was carried out.Histological patterns weren't related to metastasis size or other clinical features however pattern C metastases showed a significant worst disease free survival (DFS). KRAS mutations were observed in 39 % of patients. Mutations in KRAS codon 13 resulted significantly associated with synchronous metastasis and poor prognosis. No mutations were identified in exon 2 NRAS gene whilst 1.4 % harboured a mutation in BRAF. To our knowledge this is the first study that investigates in a large series of CLM histological growth patterns, molecular alterations and their relationship to prognosis. Our data suggest a prognostic role in CLM of KRAS specific mutations and histopathological patterns.

Subxifoid versus transthoracic thoracoscopic lobectomy: Results of a retrospective analysis before and after matching analysis.

BACKGROUND: Here, we report our initial experience with subxifoid video-assisted thoracoscopic surgery (SVATS) lobectomy for the management of primary lung cancer, and compared the outcomes of SVATS with those of conventional transthoracic VATS (CVATS) lobectomies to validate its feasibility and usefulness. METHODS: The clinical data of consecutive patients undergoing VATS lobectomy via SVATS or CVATS for lung cancer were retrospectively compared. The endpoints were to evaluate the statistical differences in surgical results, postoperative pain (measured with visual analog scale [VAS] scores at 8 hours, Day 1, Day 2, Day 3, at discharge, one month and three months after surgery) and paresthesia (measured at one- month, and three months after surgery). The two groups were compared before and after matching analysis. RESULTS: Our study population included 223 patients: 84 in the SVATS and 139 in the CVATS group. The two groups were not comparable for sex (P = 0.001), preoperative comorbidity as cardiopathy (P = 0.007), BMI value (P = 0.003), left-sided procedure (P = 0.04), tumor stage (P = 0.04), and tumor size (P = 0.002). These differences were overcome by propensity score matching (PSM) analysis that yielded two well-matched groups which included 61 patients in each group. Surgical outcomes including blood loss, hospital stay and complications were similar before and after matching analysis, but SVATS compared to CVATS was associated with longer operative time before (159 ± 13 vs. 126 ± 6.3, P < 0.0001), and after matching analysis (161 ± 23 vs. 119 ± 8.3; P < 0.0001) and significant reduction of postoperative pain during the different time-points (P < 0.001), and paresthesia at one (P = 0.001), and three months (P < 0.0001). CONCLUSIONS: SVATS lobectomy is a feasible and safe strategy with surgical outcomes similar to CVATS lobectomy but with less postoperative pain and paresthesia. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Subxifoid thoracoscopic lobectomy is a feasible and safe procedure, with potential benefits in terms of postoperative pain and paresthesia compared to conventional thoracoscopic lobectomy Our results showed that surgical outcomes including blood loss, hospital stay, morbidity and mortality are similar but subxifoid thoracoscopy was associated with significant reduction of postoperative pain and paresthesia. WHAT THIS STUDY ADDS: Subxifoid thoracoscopy is a safe procedure; compared to conventional transthoracic thoracoscopy, it avoids intercostal incisions, and spares nerve trauma, resulting in a reduction of postoperative pain and paresthesia.

Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19.

BackgroundMitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether circulating cell-free MT-DNA quantitation could be used to predict the risk of poor COVID-19 outcomes remains undetermined.MethodsWe measured circulating MT-DNA levels in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at hospital presentation. Our primary outcome was mortality. Intensive care unit (ICU) admission, intubation, vasopressor, and renal replacement therapy requirements were secondary outcomes. Multivariate regression analysis determined whether MT-DNA levels were independent of other reported COVID-19 risk factors. Receiver operating characteristic and area under the curve assessments were used to compare MT-DNA levels with established and emerging inflammatory markers of COVID-19.ResultsCirculating MT-DNA levels were highly elevated in patients who eventually died or required ICU admission, intubation, vasopressor use, or renal replacement therapy. Multivariate regression revealed that high circulating MT-DNA was an independent risk factor for these outcomes after adjusting for age, sex, and comorbidities. We also found that circulating MT-DNA levels had a similar or superior area under the curve when compared against clinically established measures of inflammation and emerging markers currently of interest as investigational targets for COVID-19 therapy.ConclusionThese results show that high circulating MT-DNA levels are a potential early indicator for poor COVID-19 outcomes.FundingWashington University Institute of Clinical Translational Sciences COVID-19 Research Program and Washington University Institute of Clinical Translational Sciences (ICTS) NIH grant UL1TR002345.

Intraoperative cardiac function assessment by transesophageal echocardiography versus FloTrac/Vigileo™ system during pectus excavatum surgical repair.

BACKGROUND: Pectus excavatum (PE), a congenital deformity of the chest wall, can lead to cardiac compression and related symptoms. PE surgical repair can improve cardiac function. Intraoperative transesophageal echocardiography (TEE) has been successfully employed to assess intraoperative hemodynamic variations in patients undergoing PE repair. FloTrac/Vigileo™ system (Edwards Life-sciences Irvine, CA) (FT/V) is a minimally invasive cardiac output monitoring system. This retrospective study aimed to assess hemodynamic changes in surgical repair of PE using FT/V and concordance with parameters measured by TEE. RESULTS: N=19 patients submitted to PE repair via Ravitch or Nuss technique were enrolled. Intraoperative cardiac assessments simultaneously obtained via TEE and FT/V system were investigated. The agreement between TEE-derived cardiac output (CO-TEE) and FT/V system parameter (COAP) was evaluated. The relationship between COTEE and COAP was analyzed for all data using linear regression analysis. A significant correlation between COAP and COTEE values (R = 0.65, p < 0.001) was found. Bland-Altman analysis of COAP and COTEE showed a bias of 0.13 L/min and a limit of agreement of - 2.33 to 2.58 L/min, with a percentage error of 48%. Intraoperative measurements by TEE and FT/V both showed a significant increase in CO after surgical correction of PE (p < 0.005). CONCLUSIONS: FT/V system compared to TEE in hemodynamic monitoring during PE surgery yielded clinically unacceptable results due to a high percentage error. After surgical correction of PE, CO, measured by TEE and FT/V, significantly improved.

Early Induction of Bedside Pneumoperitoneum in the Management of Residual Pleural Space and Air Leaks After Pulmonary Resection.

BACKGROUND: The pneumoperitoneum to treat prolonged air leaks or pleural space problems after pulmonary resection has been successfully used for decades. The aim of the study is to describe our experience with the early induction of therapeutic pneumoperitoneum (TP). METHODS: We reviewed the data of 103 consecutive patients undergoing TP between September 2011 and September 2019. Patients were divided into two groups according to the time of the induction of TP: early application (≥72 h) and standard application (>72 h). RESULTS: In total, 52 early TP and 51 standard TP were analyzed. The median time of TP induction was 2 (1-3) versus 8 (5-11) postoperative days (POD) (p < 0.001). The time for obliteration of the residual pleural space (7 vs.9 days, p = 0.805) and the time of resolution of the air leaks (14 vs. 16 days, p = 0.663) didn't differ between the two groups, but a favorable trend was observed in the early group. The hospital stay was lower for patients undergoing early pneumoperitoneum: 9 versus 18 days (p < 0.001). The multivariate analysis showed that POD of induction of TP (p < 0.001), time of resolution of the air leak (p < 0.001) and Heimlich valve (p = 0.002) were independent variables associated with the hospital stay. CONCLUSIONS: The use of TP whenever a space problem or air leaks occur after pulmonary resections is safe and effective. Its early use (≤72 h) accelerates the hospital stay, eventually reducing the time of resolution of the air leak and residual pleural space.

Circulating Mitochondrial DNA is an Early Indicator of Severe Illness and Mortality from COVID-19.

Mitochondrial DNA (MT-DNA) are intrinsically inflammatory nucleic acids released by damaged solid organs. Whether the appearance of cell-free MT-DNA is linked to poor COVID-19 outcomes remains undetermined. Here, we quantified circulating MT-DNA in prospectively collected, cell-free plasma samples from 97 subjects with COVID-19 at the time of hospital presentation. Circulating MT-DNA were sharply elevated in patients who eventually died, required ICU admission or intubation. Multivariate regression analysis revealed that high circulating MT-DNA levels is an independent risk factor for all of these outcomes after adjusting for age, sex and comorbidities. Additionally, we found that circulating MT-DNA has a similar or superior area-under-the curve when compared to clinically established measures of systemic inflammation, as well as emerging markers currently of interest as investigational targets for COVID-19 therapy. These results show that high circulating MT-DNA levels is a potential indicator for poor COVID-19 outcomes.

Cardio-Pulmonary Changes After Bronchoscopic Lung Volume Reduction with Endobronchial One-Way Valves.

INTRODUCTION: To evaluate the cardio-pulmonary hemodynamics changes before and after valve treatment, and their correlation with lobe volume reduction. METHODS: This retrospective multicentre study included consecutive patients undergoing bronchoscopic valve treatment for heterogeneous emphysema. In addition to standard functional evaluation, patients underwent cardiac evaluation by Doppler trans-thoracic echocardiography. The difference in respiratory and cardio-pulmonary hemodynamics indexes before and 3-month after the procedure, and their relationship with changes in lobar volume were evaluated. RESULTS: Seventy-seven patients were included in the study; of these 13 (17%) presented pulmonary hypertension. Only patients with target lobar volume reduction ≥ 563 mL (n = 50) presented a significant improvement of forced expiratory volume in one second, residual volume, 6 min-walk test, and St. George's Respiratory Questionnaire score; a significant reduction of pulmonary artery pressure, and an improvement of left and right ventricle end-systolic volume; of left and right ventricle end-diastolic volume, and of left and right ventricle stroke volume. The change in residual volume was significantly correlated with changes in forced expiratory volume in one second (r = 0.68; p < 0.001); in 6 min-walk test (r = 0.71; p < 0.001); in St. George's Respiratory Questionnaire (r = 0.54; p < 0.001); in pulmonary artery pressure (r = 0.39; p = 0.001), in left (r = 0.28; p = 0.01) and right (r = 0.33; p = 0.002) ventricle end-systolic volume, in left (r = - 0.29; p = 0.008) and right (r = - 0.34; p = 0.007) end-diastolic volume, and in left (r = - 0.76; p = 0.009) and right (r = - 0.718; p = 0.001) ventricle stroke volume. CONCLUSION: Bronchoscopic valve treatment seemed to have positive effects on cardio-pulmonary hemodynamics, and these changes were correlated with reductions of lobar volume.

Surgical treatment of lung cancer with adjacent lobe invasion in relation to fissure integrity.

BACKGROUND: Tumor with adjacent lobe invasion (T-ALI) is an uncommon condition. Controversy still exists regarding the optimal resection of adjacent lobe invasion, and the prognostic value in relation to fissure integrity at the tumor invasion point. The aims of this paper were to evaluate the prognosis of T-ALI with regard to fissure integrity, and type of resection. METHODS: This was a retrospective multicenter study which included all consecutive patients with T-ALI undergoing surgical treatment. Based on radiological, intraoperative and histological findings, T-ALI patients were differentiated into two groups based on whether the fissure was complete (T-ALI-A group) or incomplete (T-ALI-D Group) at the level of tumor invasion point. Clinico-pathological features and survival of two study groups were analyzed and compared. RESULTS: Study population included 135 patients, of these 98 (72%) were included into T-ALI-A group, and 37 (38%) into T-ALI-D Group. T-ALI-D patients had better overall survival than T-ALI-A patients (63.9 ± 7.0 vs. 48.9 ± 3.9; respectively, P = 0.01) who presented with a higher incidence of lymph node involvement (35% vs. 4%; P = 0.004), and recurrence rate (43% vs. 16%; P = 0.01). At multivariable analysis, T-ALI-D (P = 0.01), pN0 stage (P = 0.0002), and pT≤5 cm (P = 0.0001) were favorable survival prognostic factors. CONCLUSIONS: T-ALI-D presented a better prognosis than T-ALI-A while extent of resection had no effect on survival. Thus, in patients with small T-ALI-D and without lymph node involvement, sublobar resection of adjacent lobe rather than lobectomy could be indicated. KEY POINTS: The extent of resection of adjacent lobe had no effect on survival while T-ALI-D, pN0 stage, and pT≤5 cm were significant prognostic factors. In patients with small T-ALI-D and without lymph node involvement, sublobar resection of adjacent lobe could be indicated as an alternative to lobectomy.

Complications related to endoscopic lung volume reduction for emphysema with endobronchial valves: results of a multicenter study.

BACKGROUND: Despite bronchoscopic lung volume reduction (BLVR) with valves is a minimally invasive treatment for emphysema, it can associate with some complications. We aimed at evaluating the rate and type of complications related to valve treatment and their impact on clinical outcomes. METHODS: It is a retrospective multicenter study including all consecutive patients with severe heterogeneous emphysema undergoing BLVR with endobronchial valve treatment and developed any complications related to this procedure. The type of complication, the time of onset, the treatment required and the out-come were evaluated. Response to treatment was assessed according to the minimal clinically important difference (MCID) as follows: an improvement of ≥15% in forced expiratory volume in one second (FEV1); of -8% in residual volume (RV); of ≥26 m in 6-minnute walking distance (6MWD); and of ≥4 points on the St. George's Respiratory Questionnaire (SGRQ). Target lobe volume reduction (TLVR) ≥350 mL was considered significant. RESULTS: One hundred and seven out of 423 (25.3%) treated patients had complications related to valve treatment including pneumothorax (17.3%); pneumonia (1.7%), chronic obstructive pulmonary disease (COPD) exacerbation (0.9%), respiratory failure (1.4%), valve migration (2.1%), and hemoptysis (1.9%). In all cases complications resolved with appropriate treatment including removal of valves in 21/107 cases (19.6%). Patients with TLVR ≥350 mL (n=64) vs. those <350 mL (n=43) had a statistically significant higher improvement in FEV1 (19.0%±3.9% vs. 3.0%±0.9%; P=0.0003); in RV (-10.0%±4.8% vs. -4.0%±2.9%; P=0.002); in 6MWD (33.0±19.0 vs. 12.0±6.3 metres; P=0.001); and in SGRQ (-15.0±2.9 vs. -8.0±3.5 points; P=0.01). Only patients with TLVR ≥350 mL met or exceeded the MCID cut-off criteria for FEV1 (19.0%±3.9%), RV (-10.0%±4.8%), 6MWT (33.0±19.0 metres), and SGQR (-15.0±2.9 points). Five patients (1.2%) died during follow-up for causes not related to valves treatment neither to any of the complications described. CONCLUSIONS: Valve treatment is a safe and reversible procedure. The presence of complications seems not to have a significant impact on clinical outcome in patients with lobar atelectasis. Due to poor clinical conditions and possible complications, BLVR should be performed in high volume centers with a multidisciplinary approach.