An in-silico analysis reveals further evidence of an aggressive subset of lung carcinoids sharing molecular features of high-grade neuroendocrine neoplasms.

Little is known as to whether there may be any pathogenetic link between pulmonary carcinoids and neuroendocrine carcinomas (NECs). A gene signature we previously found to cluster pulmonary carcinoids, large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), and which encompassed MEN1, MYC, MYCL1, RICTOR, RB1, SDHA, SRC and TP53 mutations or copy number variations (CNVs), was used to reclassify an independent cohort of 54 neuroendocrine neoplasms (NENs) [31 typical carcinoids (TC), 11 atypical carcinoids (AC) and 12 SCLC], by means of transcriptome and mutation data. Unsupervised clustering analysis identified two histology-independent clusters, namely CL1 and CL2, where 17/42 (40.5%) carcinoids and all the SCLC samples fell into the latter. CL2 carcinoids affected survival adversely, were enriched in T to G transversions or T > C/C > T transitions in the context of specific mutational signatures, presented with at least 1.5-fold change (FC) increase of gene mutations including TSC2, SMARCA2, SMARCA4, ERBB4 and PTPRZ1, differed for gene expression and showed epigenetic changes in charge of MYC and MTORC1 pathways, cellular senescence, inflammation, high-plasticity cell state and immune system exhaustion. Similar results were also found in two other independent validation sets comprising 101 lung NENs (24 carcinoids, 21 SCLC and 56 LCNEC) and 30 carcinoids, respectively. We herein confirmed an unexpected sharing of molecular traits along the spectrum of lung NENs, with a subset of genomically distinct aggressive carcinoids sharing molecular features of high-grade neuroendocrine neoplasms.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: An Analysis of 5721 Cases.

OBJECTIVE: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). SUMMARY BACKGROUND DATA: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. RESULTS: A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS ( P < 0.0001) and OL ( P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P <0.02). Compared to VATS, RL had lower conversion rate ( P <0.0001), shorter hospital stay ( P <0.0001) and a lower postoperative transfusion rate ( P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. CONCLUSIONS: RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: Survival Analysis of 6646 Cases.

OBJECTIVE: The aim of this study was to analyze overall survival (OS) of robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VATS), and open lobectomy (OL) performed by experienced thoracic surgeons across multiple institutions. SUMMARY BACKGROUND DATA: Surgeons have increasingly adopted RL for resection of early-stage lung cancer. Comparative survival data following these approaches is largely from single-institution case series or administrative data sets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. Consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Induction therapy patients were excluded. The propensity-score method of inverse-probability of treatment weighting was used to balance baseline characteristics. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazard models were used to evaluate association among OS and relevant risk factors. RESULTS: A total of 2789 RL, 2661 VATS, and 1196 OL cases were included. The unadjusted 5-year OS rate was highest for OL (84%) followed by RL (81%) and VATS (74%); P =0.008. Similar trends were also observed after inverse-probability of treatment weighting adjustment (RL 81%; VATS 73%, OL 85%, P =0.001). Multivariable Cox regression analyses revealed that OL and RL were associated with significantly higher OS compared with VATS (OL vs. VATS: hazard ratio=0.64, P <0.001 and RL vs. VATS: hazard ratio=0.79; P =0.007). CONCLUSIONS: Our finding from this large multicenter study suggests that patients undergoing RL and OL have statistically similar OS, while the VATS group was associated with shorter OS. Further studies with longer follow-up are necessary to help evaluate these observations.

The diagnostic utility of inspiratory-expiratory radiography for the assessment of phrenic nerve palsy associated with brachial plexus injury.

BACKGROUND: The phrenic nerve is commonly injured with trauma to the brachial plexus. Hemi-diaphragmatic paralysis may be well-compensated in healthy individuals at rest but can be associated with persistent exercise intolerance in some patients. This study aims to determine the diagnostic value of inspiratory-expiratory chest radiography compared to intraoperative stimulation of the phrenic nerve for assessing phrenic nerve injury associated with brachial plexus injury. METHODS: Over a 21-year period, the diagnostic utility of three-view inspiratory-expiratory chest radiography for identification of phrenic nerve injury was determined by comparison to intraoperative phrenic nerve stimulation. Multivariate regression analysis was used to identify independent predictors of phrenic nerve injury and having an incorrect radiographic diagnosis. RESULTS: A total of 237 patients with inspiratory-expiratory chest radiography underwent intraoperative testing of phrenic nerve function. Phrenic nerve injury was present in approximately one-fourth of cases. Preoperative chest radiography had a sensitivity of 56%, specificity of 93%, positive predictive negative of 75%, and negative predictive value of 86% for identification of a phrenic nerve palsy. Only C5 avulsion was found to be a predictor of having an incorrect diagnosis of phrenic nerve injury on radiography. CONCLUSION: While inspiratory-expiratory chest radiography has good specificity for detecting phrenic nerve injuries, a high number of false negatives suggest that it should not be relied upon for routine screening of dysfunction after traumatic brachial plexus injury. This is likely multifactorial and relates to variation in diaphragm shape and position, as well as limitations regarding static image interpretation of a dynamic process.

Optimizing clinical cytology touch preparations for next generation sequencing.

Intraoperative diagnosis is routinely performed on cytology touch preparations (TPs) from core needle biopsies (CNBs). Current interest promotes their utility as an important source of patient tissue for clinical genomic testing. Herein we present whole genome structural variant analysis (SVA) from mate-pair sequencing (MPseq) and whole exome sequencing (WES) mutation calling in DNA directly whole genome amplified (WGA) from TPs. Chromosomal copy changes and somatic DNA junction detection from MPseq of TPs were highly consistent with associated CNBs and bulk resected tissues in all cases. While increased frequency coverage noise from limitations of amplification of limited sample input was significant, this was effectively compensated by natural tumor enrichment during the TP process, which also enhanced variant detection and loss of heterozygosity evaluations from WES. This novel TP methodology enables expanded utility of frequently limited CNB for both clinical and research genomic testing.

Computational prediction of cancer-gene function.

Most cancer genes remain functionally uncharacterized in the physiological context of disease development. High-throughput molecular profiling and interaction studies are increasingly being used to identify clusters of functionally linked gene products related to neoplastic cell processes. However, in vivo determination of cancer-gene function is laborious and inefficient, so accurately predicting cancer-gene function is a significant challenge for oncologists and computational biologists alike. How can modern computational and statistical methods be used to reliably deduce the function(s) of poorly characterized cancer genes from the newly available genomic and proteomic datasets? We explore plausible solutions to this important challenge.

Hyperoxia-induced changes in estradiol metabolism in postnatal airway smooth muscle.

Supplemental oxygen, used to treat hypoxia in preterm and term neonates, increases the risk of neonatal lung diseases, such as bronchopulmonary dysplasia (BPD) and asthma. There is a known sex predilection for BPD, but the underlying mechanisms are not clear. We tested the hypothesis that altered, local estradiol following hyperoxia contributes to pathophysiological changes observed in immature lung. In human fetal airway smooth muscle (fASM) cells exposed to normoxia or hyperoxia, we measured the expression of proteins involved in estrogen metabolism and cell proliferation responses to estradiol. In fASM cells, CYP1a1 expression was increased by hyperoxia, whereas hyperoxia-induced enhancement of cell proliferation was blunted by estradiol. Pharmacological studies indicated that these effects were attributable to upregulation of CYP1a1 and subsequent increased metabolism of estradiol to a downstream intermediate 2-methoxyestradiol. Microarray analysis of mouse lung exposed to 14 days of hyperoxia showed the most significant alteration in CYP1a1 expression, with minimal changes in expression of five other genes related to estrogen receptors, synthesis, and metabolism. Our novel results on estradiol metabolism in fetal and early postnatal lung in the context of hyperoxia indicate CYP1a1 as a potential mechanism for the protective effect of estradiol in hyperoxia-exposed immature lung, which may help explain the sex difference in neonatal lung diseases.

Preoperative statin administration does not protect against early postoperative acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Statins have been shown to possess antiinflammatory and immunomodulatory effects. In this study, we sought to determine if preoperative statin therapy is associated with a reduced frequency of postoperative acute respiratory distress syndrome (ARDS) in surgical populations at increased risk of developing ARDS. METHODS: We performed a retrospective cohort evaluation of the association between preoperative statin therapy and early postoperative ARDS in patients undergoing elective high-risk thoracic and aortic vascular surgery. The association between preoperative statin therapy and postoperative ARDS was assessed using propensity-adjusted analyses to control for indication bias and confounding factors. RESULTS: Of 1845 patients, 722 were receiving preoperative statin therapy. One hundred twenty patients developed postoperative ARDS. Frequencies of ARDS among those receiving statin therapy versus those who were not was 7.2% and 6.1%, respectively (OR = 1.20; 95% CI, 0.83-1.75; P = 0.330). Neither the stratified propensity score analysis (pooled OR 0.93; 95% CI, 0.60-1.43) nor matched analysis (OR = 0.78; 95% CI, 0.48-1.27) identified a statistically significant association between preoperative statin administration and postoperative ARDS. When compared to matched controls, patients who developed postoperative ARDS did not differ in mortality (7.7% vs 8.8%, P = 0.51), hospital length of stay (21 days vs 15 days, P = 0.21), or ventilator-free days (24 days vs 25 days, P = 0.62). CONCLUSIONS: In patients undergoing high-risk surgery, preoperative statin therapy was not associated with a statistically significant reduction in postoperative ARDS. These results do not support the use of statins as prophylaxis against ARDS in patients undergoing high-risk surgery.

Esophagectomy Enhanced Recovery After Surgery Initiative Results in Improved Outcomes.

BACKGROUND: Esophagectomy for esophageal cancer is a procedure with high morbidity and mortality. This study developed a Multidisciplinary Esophagectomy Enhanced Recovery Initiative (MERIT) pathway and analyzed implementation outcomes in a single institution. METHODS: The MERIT pathway was developed as a practice optimization and quality improvement initiative. Patients were studied from November 1, 2021 to June 20, 2022 and were compared with historical control subjects. The Wilcoxon rank sum test and the Fisher exact test were used for statistical analysis. RESULTS: The study compared 238 historical patients (January 17, 2017 to December 30, 2020) with 58 consecutive MERIT patients. There were no significant differences between patient characteristics in the 2 groups. In the MERIT group, 49 (85%) of the patients were male, and their mean age was 65 years (range, 59-71 years). Most cases were performed for esophageal cancer after neoadjuvant therapy. Length of stay improved by 27% from 11 to 8 days (P = .27). There was a 12% (P = .05) atrial arrhythmia rate reduction, as well as a 9% (P = .01) decrease in postoperative ileus. Overall complications were reduced from 54% to 35% (-19%; P = .01). CONCLUSIONS: This study successfully developed and implemented an enhanced recovery after surgery pathway for esophagectomy. In the first year, study investigators were able to reduce overall complications, specifically atrial arrhythmias, and postoperative ileus.

The 2023 American Association for Thoracic Surgery (AATS) Expert Consensus Document: Management of subsolid lung nodules.

OBJECTIVE: Lung cancers that present as radiographic subsolid nodules represent a subtype with distinct biological behavior and outcomes. The objective of this document is to review the existing literature and report consensus among a group of multidisciplinary experts, providing specific recommendations for the clinical management of subsolid nodules. METHODS: The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an international, multidisciplinary expert panel composed of radiologists, pulmonologists, and thoracic surgeons with established expertise in the management of subsolid nodules. A focused literature review was performed with the assistance of a medical librarian. Expert consensus statements were developed with class of recommendation and level of evidence for each of 4 main topics: (1) definitions of subsolid nodules (radiology and pathology), (2) surveillance and diagnosis, (3) surgical interventions, and (4) management of multiple subsolid nodules. Using a modified Delphi method, the statements were evaluated and refined by the entire panel. RESULTS: Consensus was reached on 17 recommendations. These consensus statements reflect updated insights on subsolid nodule management based on the latest literature and current clinical experience, focusing on the correlation between radiologic findings and pathological classifications, individualized subsolid nodule surveillance and surgical strategies, and multimodality therapies for multiple subsolid lung nodules. CONCLUSIONS: Despite the complex nature of the decision-making process in the management of subsolid nodules, consensus on several key recommendations was achieved by this American Association for Thoracic Surgery expert panel. These recommendations, based on evidence and a modified Delphi method, provide guidance for thoracic surgeons and other medical professionals who care for patients with subsolid nodules.

Progress in genome-inspired treatment decisions for multifocal lung adenocarcinoma.

INTRODUCTION: Multifocal lung adenocarcinoma (MFLA) is becoming increasingly recognized as a distinct subset of lung cancer, with unique biology, disease course, and treatment outcomes. While definitions remain controversial, MFLA is characterized by the development and concurrent presence of multiple independent (non-metastatic) lesions on the lung adenocarcinoma spectrum. Disease progression typically follows an indolent course measured in years, with a lower propensity for nodal and distant metastases than other more common forms of non-small cell lung cancer. AREAS COVERED: Traditional imaging and histopathological analyses of tumor biopsies are frequently unable to fully characterize the disease, prompting interest in molecular diagnosis. We highlight some of the key questions in the field, including accurate definitions to identify and stage MLFA, molecular tests to stratify patients and treatment decisions, and the lack of clinical trial data to delineate best management for this poorly understood subset of lung cancer patients. We review the existing literature and progress toward a genomic diagnosis for this unique disease entity. EXPERT OPINION: Multifocal lung adenocarcinoma behaves differently than other forms of non-small cell lung cancer. Progress in molecular diagnosis may enhance potential for accurate definition, diagnosis, and optimizing treatment approach.

Impact of FDG PET Standardized Uptake Value in Resected Clinical Stage IA Non-Small Cell Lung Cancer.

BACKGROUND: A significant proportion of patients with clinical stage IA non-small cell lung cancer (NSCLC) experience will recurrence and decreased survival after surgery. This study examined the impact of preoperative primary tumor positron emission tomography (PET) scan maximum standardized uptake value (SUVmax) on oncologic outcomes after surgery. METHODS: This was a retrospective review of 251 patients who underwent surgical treatment of clinical stage IA NSCLC at an academic medical center (2005-2014). Patients were classified according to PET SUVmax level (low vs high) for analysis of upstaging, tumor recurrence, and overall survival. RESULTS: Median SUVmax values were higher in squamous cell carcinoma than in adenocarcinoma (median 3.3 vs 7.2; P < .0001). There were 109 (43.4%) patients in the SUVmax low group and 142 (56.6%) in the SUVmax high group. Patients with SUVmax high had larger tumors. SUVmax high was associated with higher rates of nodal upstaging (16.2% vs 4.6% in SUVmax low; P = .004), particularly in N1 nodes. SUVmax high was independently associated with nodal upstaging (adjusted odds ratio, 3.95; 95% CI, 1.36-11.46; P = .011). SUVmax high was associated with time to recurrence (hazard ratio, 1.62; 95% CI, 1.03-2.54; P = .036), but this association was lost on multivariable analysis (hazard ratio, 1.52; 95% CI, 0.91-2.54; P = .106). SUVmax was not associated with overall survival. CONCLUSIONS: Preoperative PET SUVmax level is strongly associated with nodal upstaging, particularly in N1 nodes, in patients with clinical stage IA NSCLC who undergo resection. PET SUVmax should be regarded as a risk factor when considering candidacy for sublobar resections and in future trials involving patients with stage I NSCLC.

Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer.

BACKGROUND: Long-term survival in esophagectomy patients with esophageal cancer is low due to tumor-related characteristics, with few reports of modifiable variables influencing outcome. We identified determinants of overall survival, time to recurrence, and disease-free survival in this patient cohort. METHODS: Adult patients who underwent esophagectomy for primary esophageal cancer from January 5, 2000, through December 30, 2010, at our institution were identified. Univariate Cox models and multivariable logistic regression analyses were used to identify associations between modifiable and unmodifiable patient and clinical variables and outcome of survival for the total cohort and a subgroup with locally advanced disease. RESULTS: We identified 870 patients with esophageal cancer who underwent esophagectomy. The median follow-up time was 15 years, and the 15-year overall survival rate was 25.2%, survival free of recurrence was 57.96%, and disease-free survival was 24.21%. Decreased overall survival was associated with the following unmodifiable variables: older age, male sex, active smoking status, history of coronary artery disease, advanced clinical stage, and tumor location. Decreased overall survival was associated with the following modifiable variables: use of neoadjuvant therapy, advanced pathologic stage, resection margin positivity, surgical reintervention, and blood transfusion requirement. The overall survival probability 6 years after esophagectomy was 0.920 (95% CI, 0.895-0.947), and time-to-recurrence probability was 0.988 (95% CI, 0.976-1.000), with a total of 17 recurrences and 201 deaths. CONCLUSIONS: Once patients survive 5 years, recurrence is rare. Long-term survival can be achieved in high-volume centers adhering to National Comprehensive Cancer Network guidelines using multidisciplinary care teams that is double what has been previously reported in the literature from national databases.

MicroRNA-mRNA interactions in a murine model of hyperoxia-induced bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a chronic lung disease of premature neonates characterized by arrested pulmonary alveolar development. There is increasing evidence that microRNAs (miRNAs) regulate translation of messenger RNAs (mRNAs) during lung organogenesis. The potential role of miRNAs in the pathogenesis of BPD is unclear. RESULTS: Following exposure of neonatal mice to 80% O2 or room air (RA) for either 14 or 29 days, lungs of hyperoxic mice displayed histological changes consistent with BPD. Comprehensive miRNA and mRNA profiling was performed using lung tissue from both O2 and RA treated mice, identifying a number of dynamically regulated miRNAs and associated mRNA target genes. Gene ontology enrichment and pathway analysis revealed that hyperoxia modulated genes involved in a variety of lung developmental processes, including cell cycle, cell adhesion, mobility and taxis, inflammation, and angiogenesis. MiR-29 was prominently increased in the lungs of hyperoxic mice, and several predicted mRNA targets of miR-29 were validated with real-time PCR, western blotting and immunohistochemistry. Direct miR-29 targets were further validated in vitro using bronchoalveolar stem cells. CONCLUSION: In newborn mice, prolonged hyperoxia induces an arrest of alveolar development similar to that seen in human neonates with BPD. This abnormal lung development is accompanied by significant increases in the levels of multiple miRNAs and corresponding decreases in the levels of predicted mRNA targets, many of which have known or suspected roles in pathways altered in BPD. These data support the hypothesis that dynamic regulation of miRNAs plays a prominent role in the pathophysiology of BPD.

Preoperative gabapentin for acute post-thoracotomy analgesia: a randomized, double-blinded, active placebo-controlled study.

BACKGROUND: The role of preoperative gabapentin in postoperative pain management is not clear, particularly in patients receiving regional blockade. Patients undergoing thoracotomy benefit from epidural analgesia but still may experience significant postoperative pain. We examined the effect of preoperative gabapentin in thoracotomy patients. METHODS: Adults undergoing elective thoracotomy were enrolled in this prospective, randomized, double-blinded, placebo-controlled study, and randomly assigned to receive 600 mg gabapentin or active placebo (12.5 mg diphenhydramine) orally within 2 hours preoperatively. Standardized management included thoracic epidural infusion, intravenous patient-controlled opioid analgesia, acetaminophen and ketorolac. Pain scores, opioid use and side effects were recorded for 48 hours. Pain was also assessed at 3 months. RESULTS: One hundred twenty patients (63 placebo and 57 gabapentin) were studied. Pain scores did not significantly differ at any time point (P = 0.53). Parenteral and oral opioid consumption was not significantly different between groups on postoperative day 1 or 2 (P > 0.05 in both cases). The frequency of side effects such as nausea and vomiting or respiratory depression was not significantly different between groups, but gabapentin was associated with decreased frequency of pruritus requiring nalbuphine (14% gabapentin vs. 43% control group, P < 0.001). The frequency of patients experiencing pain at 3 months post-thoracotomy was also comparable between groups (70% gabapentin vs. 66% placebo group, P = 0.72). CONCLUSIONS: A single preoperative oral dose of gabapentin (600 mg) did not reduce pain scores or opioid consumption following elective thoracotomy, and did not confer any analgesic benefit in the setting of effective multimodal analgesia that included thoracic epidural infusion.

Serial evaluation of segmental esophageal reconstruction using a polyurethane scaffold in a pig model.

Background: Many esophageal pathologies are clinically treated by resection and reconstruction of the esophagus. Surgical esophagectomy remains a morbid procedure and despite minimally invasive advances, has changed little in decades. Novel approaches to esophageal segmental resection and reconstruction are an unmet need. Methods: Circumferential thoracic esophageal transection was performed in both male and female pigs and the defects reconstructed using 5 or 10 cm polyurethane (PU) tubular grafts and stented. A subset were treated with stent only. Animals were survived to 14, 30, 60, and 399 days. Tissues were evaluated histologically, and via non-invasive serial endoscopy and contrast swallowing studies in long-term animals. Results: Luminal patency was achieved in all animals with no clinical evidence of leak. In short-term animals, there was healing noted in all cases with a variably sized region of ulceration remaining at the most central part of the repaired tube (between the proximal and distal anastomosis). In four long-term animals following stent removal, two resumed normal diet and thrived, while two animals were euthanized prior to the proposed endpoint because of stricture formation and inability to tolerate a normal diet. Re-epithelialization was observed in all groups, and more complete over time. Conclusions: The PU scaffold provides a matrix across which formation of new tissue can occur. The mechanisms through which this happens remain unclear, but likely a combination of fibrosis and tissue contraction, in conjunction with new tissue formation.

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer.

OBJECTIVES: Pembrolizumab is a programmed death receptor-1 masking antibody approved for metastatic non-small cell lung cancer. This Phase 2 study (NCT02818920) of neoadjuvant pembrolizumab in non-small cell lung cancer had a primary end point of safety and secondary end points of efficacy and correlative science. METHODS: Patients with untreated clinical stage IB to IIIA non-small cell lung cancer were enrolled. Two cycles of pembrolizumab (200 mg) were administered before surgery. Standard adjuvant chemotherapy and radiation were encouraged but not required. Four cycles of adjuvant pembrolizumab were provided. RESULTS: Of 35 patients enrolled, 30 received neoadjuvant pembrolizumab and 25 underwent lung resection. Only 1 patient had a delay before surgery attributed to pembrolizumab; this was due to thyroiditis. All patients underwent anatomic resection and mediastinal lymph node dissection; the majority (18/25%, 72%) of patients underwent lobectomy. Of the 25 patients, 23 had an initial minimally invasive approach (92%); 5 of these were converted to thoracotomy (21.7%). R0 resection was achieved in 22 patients (88%), and major pathologic response was observed in 7 of 25 patients (28%). The most common postoperative adverse event was atrial fibrillation, affecting 6 of 25 patients (24%). Median chest tube duration and length of stay were 3 and 4 days, respectively. One patient required readmission to the hospital within 30 days. There was no mortality within 90 days of surgery. CONCLUSIONS: In this study, pembrolizumab was safe and well tolerated in the neoadjuvant setting, and its use was not associated with excess surgical morbidity or mortality. Minimally invasive approaches are feasible in this patient population, but may be more challenging than in cases without neoadjuvant immunotherapy. Pathologic response was higher than typically observed with standard neoadjuvant chemotherapy.

Surgical management of lung cancer.

Lung cancer continues to be the most frequent cancer-related cause of death in the United States and throughout the world. Surgical resection is currently the most effective treatment in early-stage non-small-cell lung cancer, and historically the only treatment approach achieving significant cure rates. In advanced disease, therapeutic approaches involving chemotherapy and/or radiation therapy are utilized to improve prognosis, either as part of a neoadjuvant treatment approach followed by surgical resection or as definitive treatment alone. The role of surgery in locally advanced or metastatic non-small-cell lung cancer remains controversial, with more studies required to further refine the application of modern surgical techniques. For any treatment approach, thorough preoperative staging as well as careful patient selection are essential to assess the benefits and risks involved for the patient. Surgical management of early-stage non-small-cell lung cancer and its role in more advanced disease are discussed in this review.

Management of Epiphrenic Diverticula and Short-term Outcomes.

Epiphrenic diverticulum is a rare and benign condition with significant surgical morbidity and evolving surgical management. The objective of this study was to analyze short-term clinical outcomes after surgery for epiphrenic diverticula. We conducted a retrospective cohort study in a single tertiary care center of all patients who underwent treatment for epiphrenic esophageal diverticula from June 1990 to December 2016. Data collection included demographics, operative details and short-term outcomes (esophageal leak, other complications, 30-day mortality). In addition, all preoperative imaging was reviewed by an esophageal radiologist in order to describe epiphrenic diverticula characteristics in a uniform and blinded manner. Of the 94 patients in the study, 84 patients were managed with an open surgical approach and 10 with minimally invasive techniques. Median size of diverticula was 5.5 cm and mean height above gastroesophageal junction was 4 cm. A myotomy was completed in 95% of patients and a fundoplication in 58%. The MIS group had a shorter length of stay (4 vs 6 days). Overall complication rate was 27% with an esophageal leak rate of 7% with 60% grade I leaks that sealed with conservative management. Complete resection of the diverticulum, closure of the muscle over the resection, contralateral myotomy, and consideration for partial fundoplication are common strategies utilized to surgically treat patients with epiphrenic diverticulum. Minimally invasive approaches are increasingly utilized.

Autologous blood patch pleurodesis for prolonged postoperative air leaks.

BACKGROUND: A prolonged air leak (PAL) is the most frequent complication after pulmonary resection. This study aimed to assess the safety and efficacy of autologous blood patch pleurodesis (ABPP) to treat PAL. METHODS: A prospectively maintained database identified patients with a PAL after pulmonary resection for lung cancer between 2015-2019. In this observational cohort study, clinical data were collected to retrospectively compare patients undergoing ABPP to no ABPP in a propensity-matched analysis. Kaplan Meier estimates and Cox models accounting for inverse probability weighting (IPTW) were used to assess the association of ABPP with each outcome. RESULTS: Of the 740 patients undergoing lung resection, 110 (15%) were identified as having a PAL at postoperative day (POD) 5. There was no difference between baseline characteristics among those undergoing ABPP (n=34) versus no ABPP (n=76). Propensity-weighted analysis did not reveal a significant association of ABPP treatment with in-hospital complication (P=0.18), hospital length of stay (LOS) (P=0.13), or post-discharge complication (P=0.13). However, ABPP treatment was associated with a lower risk of hospital readmission [P=0.02, hazard ratio (HR) 0.16] and reoperation for air leak or empyema (P=0.05, HR 0.11). Although not statistically significant, the mean chest tube (CT) removal of 11 days for the ABPP group was less than the no ABPP group (16 days) (P=0.14, HR 1.5-2). Those treated with ABPP were less likely to be discharged with a CT (ABPP 7/34, 21% vs. no ABPP 40/76, 53%). There was no statistical difference in empyema development between groups (ABPP 0/34, 0% vs. no ABPP 4/76, 5%, P=0.39, HR 0.24). CONCLUSIONS: ABPP administration is safe compared to traditional PAL management. In a retrospective propensity-matched analysis, postoperative patients treated with ABPP required less readmission and reoperation for PAL. Larger powered randomized trials may demonstrate the magnitude of benefit from treatment with ABPP.