Tracheobronchoplasty yields long-term anatomy, function, and quality of life improvement for patients with severe excessive central airway collapse.

OBJECTIVES: This study examines the long-term anatomic and clinical effects of tracheobronchoplasty in severe excessive central airway collapse. METHODS: Included patients underwent tracheobronchoplasty for excessive central airway collapse (2002-2016). The cross-sectional area of main airways on dynamic airway computed tomography was measured before and after tracheobronchoplasty. Expiratory collapse was calculated as the difference between inspiratory and expiratory cross-sectional area divided by inspiratory cross-sectional area ×100. The primary outcome was improvement in the percentage of expiratory collapse in years 1, 2, and 5 post-tracheobronchoplasty. Secondary outcomes included mean response profile for the 6-minute walk test, Cough-Specific Quality of Life Questionnaire, Karnofsky Performance Status score, and St George Respiratory Questionnaire. Repeated-measures analysis of variance was used for statistical analyses. RESULTS: The cohort included 61 patients with complete radiological follow-up at years 1, 2, and 5 post-tracheobronchoplasty. A significant linear decrease in the percentage of expiratory collapsibility of the central airways after tracheobronchoplasty was present. Anatomic repair durability was preserved 5 years after tracheobronchoplasty, with decrease in percentage of expiratory airway collapse up to 40% and 30% at years 1 and 2, respectively. The St George Respiratory Questionnaire (74.7 vs 41.8%, P < .001) and Cough-Specific Quality of Life Questionnaire (78 vs 47, P < .001) demonstrated significant improvement at year 5 compared with baseline. Similar results were observed in the 6-minute walk test (1079 vs 1268 ft, P < .001) and Karnofsky score (57 vs 82, P < .001). CONCLUSIONS: Tracheobronchoplasty has durable effects on airway anatomy, functional status, and quality of life in carefully selected patients with severe excessive central airway collapse.

Left ventricular assist device placement in the setting of congenital VSD.

We describe the management of a 59-year-old female with an unrepaired congenital ventricular septal defect (VSD) and end stage nonischemic cardiomyopathy necessitating placement of a left ventricular assist device (LVAD) as a destination treatment. Simultaneous repair of the VSD was performed during the LVAD implantation under a beating heart. The patient remained hemodynamically stable throughout her postoperative course, without signs of hypoxia or cyanosis. Following discharge, outpatient surveillance echocardiogram demonstrated successful VSD closure and no residual shunt.

A case of fulminant myocarditis due to COVID-19 in an adolescent patient successfully treated with venous arterial ECMO as a bridge to recovery.

Emerging data suggest an association between severe acute respiratory syndrome coronavirus 2 and the development of acute myocarditis, with children and older adults being most at risk. We describe the clinical course of a previously healthy 12-year-old female who rapidly deteriorated into cardiogenic shock and arrest due to coronavirus disease 2019 induced fulminant myocarditis, necessitating venous-arterial extracorporeal membrane oxygenation as a bridge to full recovery. This case highlights the importance of early clinical recognition of myocardial involvement, and the benefits of taking a multidisciplinary approach in treating these patients.

Off pump coronary artery bypass in patients with an ejection fraction of <20%. What is our strategy?

Patients with left ventricular dysfunction and low ejection fraction (EF) are at high risk of complication and mortality after coronary artery bypass grafting (CABG). The potential success of off-pump CABG in this high-risk population has yet to be illustrated. Herein, we present our experience in regards to surgical planning and strategy on how to perform off-pump CABG in patients with very low EF.

Longitudinal Follow-up of Patients With Tracheobronchomalacia After Undergoing Tracheobronchoplasty: Computed Tomography Findings and Clinical Correlation.

PURPOSE: The purpose of this study was to evaluate intermediate and long-term changes in expiratory tracheal collapsibility by computed tomography (CT) in patients with tracheobronchomalacia following surgical treatment with tracheobronchoplasty and to correlate CT findings with clinical findings. MATERIALS AND METHODS: Between 2003 and 2016, 18 patients with tracheobronchomalacia underwent tracheobronchoplasty and were imaged preoperatively and postoperatively at both intermediate and long-term intervals. Imaging included end-inspiratory and dynamic expiratory phase scans. The cross-sectional area of the airway lumen was measured at 2 standard levels (1 cm above the aortic arch and carina). These measurements were used to calculate % collapsibility. Clinical findings recorded included a questionnaire on symptomatology and a 6-minute walk test. RESULTS: Before surgery, expiratory collapsibility of the upper trachea was 72%±25% (mean±SD) and that of the lower trachea was 68%±22%. On intermediate follow-up (mean, 1.5 y), collapsibility significantly decreased to 37%±21% at the upper trachea and 35%±19% at the lower trachea (P<0.001). On long-term follow-up (mean, 6 y), collapsibility increased to 51%±20% at the upper trachea and 47%±17% at the lower trachea and was significantly worse than on intermediate follow-up (P=0.002). However, collapsibility on long-term follow-up remained significantly lower than preoperative collapsibility (P=0.015). Clinical findings showed a similar trend as quantitative CT measurements. CONCLUSION: Expiratory tracheal collapsibility substantially decreases after tracheobronchoplasty on intermediate follow-up. At long-term follow-up, tracheal collapsibility shows a modest increase, but remains significantly lower than the preoperative baseline. Quantitative measurements from dynamic CT have the potential to play an important role as imaging biomarkers for assessing response to tracheobronchoplasty.

Frailty Characteristics Predict Respiratory Failure in Patients Undergoing Tracheobronchoplasty.

BACKGROUND: Respiratory complications are the leading cause of morbidity in patients undergoing tracheobronchoplasty, yet risk stratification systems on this population are insufficient. We investigated the association between frailty and risk of major respiratory complications after tracheobronchoplasty. METHODS: A retrospective review was made of 161 consecutive tracheobronchoplasties (October 2002 to September 2016). A frailty index was developed by the deficit-accumulation approach comprising 26 multidomain preoperative variables. The main outcome was a composite endpoint of major respiratory complications within 30 days of surgery. Odds ratio (OR) and 95% confidence interval (CI) were estimated using logistic regression. RESULTS: The cohort consisted of 103 women (64%), median age of 58 years (interquartile range, 51 to 66) and median FI of 0.25 (interquartile range, 0.1 to 0.3). Forty-eight patients (30%) had respiratory complications, the most common being respiratory failure (n = 27, 16.8%) and pneumonia (n = 25, 15.5%). Severe frailty (frailty index ≥0.33) was strongly associated with major respiratory complications (73.8% versus 2.5%; OR 58.8, 95% CI: 9.6 to 358.3). The association with severe frailty appeared stronger for respiratory failure (47.6% versus 2.5%; OR 30, 95% CI: 4.7 to 189.9) than for pneumonia (40.5% versus 0%; OR 35.2. 95% CI: 2.0 to 599.8). Further adjustment for intraoperative crystalloid volume or forced expiratory volume in 1 second moderately attenuated the association between frailty with major respiratory complications (OR 17.4. 95% CI: 2.0 to 150.8), respiratory failure (OR 13.1, 95% CI: 1.7 to 95.8), and pneumonia (OR 20.1, 95% CI: 1.1 to 341.8). CONCLUSIONS: Frailty, as indicated by frailty index, was associated with major respiratory complications, particularly respiratory failure after tracheobronchoplasty. Preoperative identification of frailty may help guide decision making for patients considering this effective, although arduous procedure.

Single-Center Experience of Tracheobronchoplasty for Tracheobronchomalacia: Perioperative Outcomes.

BACKGROUND: We present trends in practice as our experience has grown and report the postoperative morbidity and its associated factors after tracheobronchoplasty. METHODS: A retrospective cohort study was conducted of 161 patients who underwent tracheobronchoplasty from October 2002 to September 2016. The main outcome was development of a postoperative complication within 30 days of the operation. Postoperative complication events were graded using the Clavien-Dindo system. The study patients were divided into two consecutive cohorts to examine trends in systems of care. Postoperative morbidity was examined using a log-binomial regression model. RESULTS: The cohort consisted of 103 women (64%), with a median age of 58 years (interquartile range, 52 to 66 years). Postoperative morbidity occurred in 75 patients (47%). Severe complications (Clavien-Dindo grade ≥IIIa) occurred in 38 patients (24%), most of which were respiratory in nature, including 27 (17%) with respiratory failure. Median intensive care unit length of stay was 4 days (interquartile range, 3 to 5 days), with a total length of stay of 8 days (interquartile range, 6 to 11 days). In-hospital mortality occurred in 2 patients (1%). Discharge was directly to home in 68% of patients (37% without assistance and 31% with visiting nurse follow-up) and to a rehabilitation facility in 31%. After adjusting for age, sex, race, operative time, and intraoperative blood loss, forced expiratory volume in 1 second was an independent predictor (odds ratio, 0.97; 95% confidence interval, 0.95 to 0.99; p = 0.01) for postoperative morbidity. CONCLUSIONS: Despite an arduous hospital course with significant risk of severe complication, patients undergoing tracheobronchoplasty for severe tracheobronchomalacia have low risk of mortality and most are discharged directly to home.

Prophylactic use of alpha-1 adrenergic blocking agents for prevention of postoperative urinary retention: A review & meta-analysis of randomized clinical trials.

BACKGROUND: Alpha-1 adrenergic blockers used to treat postoperative urinary retention (POUR) may also have a preventative role. Here we assess the evidence behind their prophylactic use on POUR prevention. STUDY DESIGN: PRISMA guidelines were followed. All studies reviewed for eligibility, data extraction, and risk of bias assessment. Pooled risk ratios with 95% confidence intervals calculated using a random effects model. Heterogeneity assessed using Forest plots, I2 statistic and Chi-squared Cochran's Q-statistic. RESULTS: Fifteen RCTs (1732 patients) included. Prophylactic alpha-1 adrenergic blockers significantly reduced risk of POUR, 13.16% vs 30.24%, RR = 0.48 (95%CI: 0.33; 0.70, p-value = .001), without a statistically significant increase in adverse events. Substantial heterogeneity found between included studies (I2 = 65.49% [95%CI:48.49; 95.01] & Q-statistic 43.46 (p-value<.001)). Subgroup analysis revealed strong risk reduction and little heterogeneity in males (RR:0.33, 95%CI:0.23; 0.47, p-value<.001, I2:10.58) and patients receiving spinal anesthesia (RR:0.26, 95%CI:0.14; 0.46, p-value<.0001, I2 = 0%). CONCLUSION: Prophylactic alpha-1 adrenergic blockers reduce risk of POUR in males and after spinal anesthesia.

Fatal Hemoptysis After Closure of Gastrobronchial Fistula Using an Amplatzer Vascular Device.

The Amplatzer family of vascular devices has been used off-label for the treatment of complex gastrointestinal and airway fistulas. We report a case in which closure of a benign gastrobronchial fistula with the use of an Amplatzer device resulted in massive hemoptysis and death.

Current concepts in severe adult tracheobronchomalacia: evaluation and treatment.

There is increasing recognition of tracheobronchomalacia (TBM) in patients with respiratory complaints, though its true incidence in the adult population remains unknown. Most of these patients have an acquired form of severe diffuse TBM of unclear etiology. The mainstays of diagnosis are dynamic (inspiratory and expiratory) airway computed tomography (CT) scan and dynamic flexible bronchoscopy with forced expiratory maneuvers. While the prevailing definition of TBM is 50% reduction in cross-sectional area, a high proportion of healthy volunteers meet this threshold, thus this threshold fails to identify patients that might benefit from intervention. Therefore, we consider complete or near-complete collapse (>90% reduction in cross-sectional area) of the airway to be severe enough to warrant potential intervention. Surgical central airway stabilization by posterior mesh splinting (tracheobronchoplasty) effectively corrects malacic airways and has been shown to lead to significant improvement in symptoms, health-related quality of life, as well as functional and exercise capacity in carefully selected adults with severe diffuse TBM. A short-term stent trial clarifies a patient's candidacy for surgical intervention. Coordination of care between experienced interventional pulmonologists, radiologists, and thoracic surgeons is essential for optimal outcomes.

Impact of Increasing Age on Cause-Specific Mortality and Morbidity in Patients With Stage I Non-Small-Cell Lung Cancer: A Competing Risks Analysis.

Purpose To perform competing risks analysis and determine short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who had undergone resection for stage I non-small-cell lung cancer (NSCLC). Patients and Methods Of 5,371 consecutive patients who had undergone curative-intent resection of primary lung cancer at our institution (2000 to 2011), 2,186 with pathologic stage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were included in the analysis, specifically, Charlson comorbidity index, predicted postoperative (ppo) diffusing capacity of the lung for carbon monoxide, and ppo forced expiratory volume in 1 second. Cause-specific mortality analysis was performed with competing risks analysis. Results Of 2,186 patients, 1,532 (70.1%) were ≥ 65 years of age, including 638 (29.2%) ≥ 75 years of age. In patients < 65, 65 to 74, and ≥ 75 years of age, 5-year lung cancer-specific cumulative incidence of death (CID) was 7.5%, 10.7%, and 13.2%, respectively (overall, 10.4%); noncancer-specific CID was 1.8%, 4.9%, and 9.0%, respectively (overall, 5.3%). In patients ≥ 65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer-specific CID; the higher noncancer-specific, early-phase mortality was enhanced in patients ≥ 75 years of age than in those 65 to 74 years of age. Multivariable analysis showed that low ppo diffusing capacity of lung for carbon monoxide was an independent predictor of severe morbidity ( P < .001), 1-year mortality ( P < .001), and noncancer-specific mortality ( P < .001), whereas low ppo forced expiratory volume in 1 second was an independent predictor of lung cancer-specific mortality ( P = .002). Conclusion In patients who undergo curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with an increasing impact as patient age increases.

Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma: Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent Prognostic Factor.

INTRODUCTION: We previously reported the prognostic significance of the lung adenocarcinoma immune microenvironment. In this study, we preformed comprehensive analysis of immune markers and their associations with prognosis in patients with lung squamous cell carcinoma. METHODS: We reviewed surgically resected, solitary lung squamous cell carcinoma patients (n = 485; 1999-2009) who were randomly split into a training cohort (n = 331) and validation cohort (n = 154). We constructed tissue microarrays and performed immunostaining for CD3, CD45RO, CD8, CD4, FoxP3, CD20, CD68, CXCL12, CXCR4, CCR7, interleukin-7 receptor, and interleukin-12 receptor ß2. Overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model. RESULTS: Analysis of single immune cell infiltration revealed that high tumor-infiltrating CD10(+) neutrophils were associated with worse prognoses in the training cohort (p = 0.021). Analysis of biologically relevant immune cell combinations identified that patients with high CD10 neutrophil and low CD20(+) lymphocyte had a significantly worse OS (5-year OS, 42%) than those with other combinations of CD10 and CD20 (5-year OS, 62%; p < 0.001); this was confirmed in the validation cohort (p = 0.032). For the multivariate analysis, high CD10/low CD20 immune cell infiltration was an independent predictor of OS in both the training cohort (hazard ratio = 1.61, p = 0.006) and the validation cohort (hazard ratio = 1.75; p = 0.043). CONCLUSION: High CD10(+)/low CD20(+) immune cell infiltration ratio is a significant prognostic factor of lung squamous cell carcinoma. Immunomodulatory therapy of tumor-specific neutrophil and B-lymphocyte responses may have applicability in the treatment of lung squamous cell carcinoma.

Resection of Primary and Secondary Tumors of the Sternum: An Analysis of Prognostic Variables.

BACKGROUND: We sought to determine the prognostic variables associated with overall survival (OS) and recurrence-free probability (RFP) in patients with primary and secondary sternal tumors treated with surgical resection. METHODS: A retrospective analysis of patients who underwent resection of primary or secondary sternal tumors at 2 cancer institutes between 1995 and 2013 was performed. OS and RFP were estimated using the Kaplan-Meier method, and predictors of OS and RFP were analyzed using the Cox proportional hazards model. RESULTS: Sternal resection was performed in 78 patients with curative (67 [86%]) or palliative (6 [8%]) intent. Seventy-three patients (94%) had malignant tumors, of which 28 (36%) were primary and 45 (57%) were secondary malignancies. Sternal resections were complete in 13 patients (17%) and partial in 65 (83%). There were no perioperative deaths, and grade III/IV complications were noted in 17 patients (22%). The 5-year OS was 80% for patients with primary malignant tumors, 73% for patients with nonbreast secondary malignant tumors, and 58% for patients with breast tumors (p = 0.85). In the overall cohort, R0 resection was associated with prolonged 5-year OS (84% vs 20%) on univariate (p = 0.004) and multivariate (adjusted hazard ratio, 3.37; p = 0.029) analysis. On subgroup analysis, R0 resection was associated with improved OS and RFP only for patients with primary malignant tumors. CONCLUSIONS: Sternal resection can achieve favorable OS for patients with primary and secondary sternal tumors. R0 resection is associated with improved 5-year OS and RFP in patients with primary malignant tumors. We did not detect a similar effect in patients with breast or nonbreast secondary tumors.

Small RNA sequencing for profiling microRNAs in long-term preserved formalin-fixed and paraffin-embedded non-small cell lung cancer tumor specimens.

BACKGROUND: The preservation of microRNAs in formalin-fixed and paraffin-embedded (FFPE) tissue makes them particularly useful for biomarker studies. The utility of small RNA sequencing for microRNA expression profiling of FFPE samples has yet to be determined. METHODS: Total RNA was extracted from de-paraffinized and proteinase K-treated FFPE specimens (15-20 years old) of 8 human lung adenocarcinoma tumors by affinity chromatography on silica columns. MicroRNAs in the RNA preparations were quantified by the Illumina HiSeq 2000 sequencing platform with sequencing libraries prepared with the TruSeq Small RNA Sample Preparation Kit (version 2.0) to obtain unpaired reads of 50 b for small RNA fragments. MicroRNAs were also quantified using Agilent Human miRNA (release 16.0) microarrays that can detect 1,205 mature microRNAs and by quantitative reverse transcription (RT)-PCR assays. RESULTS: Between 9.1-16.9 million reads were obtained by small RNA sequencing of extracted RNA samples. Of these, only 0.6-2.3% (mean = 1.5%) represented microRNAs. The sequencing method detected 454-625 microRNAs/sample (mean = 550) compared with 200-349 (mean = 286) microRNAs detected by microarray. In Spearman correlation analyses, the average correlation coefficient for the 126 microRNAs detected in all samples by both methods was 0.37, and >0.5 for 63 microRNAs. In correlation analyses of the sequencing- and RT-PCR-based measurements, the coefficients were 0.19-0.95 (mean = 0.73) and >0.7, respectively, for 7 of 9 examined microRNAs. The average inter-replicate Spearman correlation coefficient for the sequencing method was 0.81. CONCLUSIONS: Small RNA sequencing can be used to obtain microRNA profiles of FFPE tissue specimens with performance characteristics similar to those of microarrays, in spite of the fragmentation of ribosomal and messenger RNAs that reduces the method's informative capacity. The accuracy of the method can conceivably be improved by increasing sequencing depth and/or depleting FFPE tissue RNAs of ribosomal RNA fragments.

Recent advances and clinical implications of the micropapillary histological subtype in lung adenocarcinomas.

Micropapillary (MIP) histologic subtype included in the classification of lung adenocarcinomas (ADCs) is associated with both size- and stage-independent poor prognoses. MIP pattern in lung ADCs, even at small, early stages, correlates with high lymphovascular invasion, visceral pleural invasion and lymph node metastases. Recently, we reported that patients with a MIP component are at a higher risk of locoregional recurrence after limited resection. Identification of a MIP pattern is only possible with permanent pathologic sections; preoperative imaging, cytology or intraoperative frozen section specimens remain unreliable. The intermixed, heterogenous morphology of lung ADC presents a technical challenge in investigating the molecular biology of cells with MIP morphology. A comprehensive understanding of the biology of MIP morphology is vital for therapeutic interventions.

The tumor immune microenvironment in octogenarians with stage I non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality and has increasingly become a disease of elderly patients. Elderly patients are underrepresented in clinical trials that evaluate treatments for NSCLC. It has been suggested that patients >65 years of age have less robust immune responses to infections, immunizations, and tumors compared with younger patients. With increasing focus and number of immunotherapy clinical trials for NSCLC, we investigated the relationship between patient age and the tumor immune microenvironment in NSCLC. Using tissue microarrays from 1,278 patients with surgically resected Stage I NSCLC (≤65 years [33%], 66-79 years [55%], and ≥80 years [12%]), we determined whether quantitative and qualitative immune cell infiltration in the tumor differed between younger and older patients. Furthermore, we investigated the prognostic value of immune cell infiltration with respect to recurrence in octogenarians. We found that there were no statistically significant differences between older and younger patients in tumoral immune infiltration or effector regulatory immune response ratios (FoxP3/CD3, FoxP3/CD4, and FoxP3/CD8 ratios). In octogenarians, presence of low tumoral CD68+ immune cells was an independent predictor of recurrence. In the uniform cohort of surgically selected and resected Stage I NSCLC patients, tumor immune cell infiltration among the older age group resembled other age groups. Our study provides information that supports inclusion of older age patients selected for surgical resection in neoadjuvant or adjuvant immunotherapy clinical trials for lung cancer.