A Multidisciplinary Minimally Invasive Approach Is Necessary for the Contemporary Management of Esophageal Diverticula.

Background: Esophageal diverticula were traditionally treated with open surgery, which is associated with significant morbidity and mortality rates. Management has shifted to minimally invasive approaches with several advantages. We examine outcomes in patients with esophageal diverticula treated with minimally invasive techniques by a multidisciplinary surgical team at a single center. Materials and Methods: A retrospective review of a prospectively maintained database was performed for patients who underwent minimally invasive surgery for esophageal diverticula at our institution from June 2010 to December 2022. Primary outcomes were 30-day morbidity and mortality rates. Secondary outcomes were symptom resolution, length of stay (LOS), readmission, and need for reintervention. Results: A total of 28 patients were identified. Twelve patients had pharyngeal diverticula, 7 patients had midesophageal diverticula, and 9 patients had epiphrenic diverticula. Thirty-day morbidity and readmission rates were 10.7% (3 patients), 1 pharyngeal (sepsis), 1 midesophageal (refractory nausea), and 1 epiphrenic (poor oral intake). There were no esophageal leaks. Average LOS was 2.3 days, with the pharyngeal group experiencing a significantly shorter LOS (1.3 days versus 3.4 days for midesophageal, P < .01 versus 2.8 days for epiphrenic, P < .05). Symptom resolution after initial operation was 78.6%. Reintervention rate was 17.9%, and symptom resolution after reintervention was 100%. There were no mortalities. Conclusion: This study demonstrates that esophageal diverticula can be repaired safely and efficiently when performed by a multidisciplinary team utilizing advanced minimally invasive endoscopic and robotic surgical techniques. We advocate for the management of this rare condition at a high-volume center with extensive experience in foregut surgery.

Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma.

We have previously identified alveolar type II cell as the cell-of-origin of KrasG12D-induced lung adenocarcinoma using cell lineage-specific inducible Cre mouse models. Using gain-of-function and loss-of-function genetic models, we discovered that active Notch signaling and low Sox2 levels dictate the ability of type II cells to proliferate and progress into lung adenocarcinoma upon KrasG12D activation. Here, we examine the phenotype of type II cells after Kras activation and find evidence for proliferation of cells that coexpress type I and type II markers. Three-dimensional organoid culture and transplantation studies determine that these dual-positive cells are highly plastic and tumor initiating in vivo. RNA sequencing analysis reveals that these dual-positive cells are enriched in Ras/MAPK, EGFR, and Notch pathways. Furthermore, the proliferation of these cells requires active Notch signaling and is inhibited by genetic/chemical Sox2 upregulation. Our findings could provide new therapeutic strategies to target KRAS-activated lung adenocarcinomas. SIGNIFICANCE: Identification of progenitor like tumor-initiating cells in KRAS-mutant lung adenocarcinoma may allow development of novel targeted therapeutics.

The Society of Thoracic Surgeons General Thoracic Surgery Database: 2022 Update on Outcomes and Research.

The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) remains the largest and most robust thoracic surgical database in the world. Participating sites receive risk-adjusted performance reports for benchmarking and quality improvement initiatives. The GTSD also provides several mechanisms for high-quality clinical research using data from 274 participant sites and 781,000 procedures since its inception in 2002. Participant sites are audited at random annually for completeness and accuracy. Over the last year and a half, the GTSD Task Force continued to refine the data collection process, implementing an updated data collection form in July 2021, ensuring high data fidelity while minimizing data entry burden. In addition, the STS Workforce on National Databases has supported a robust GTSD-based research program, which led to eight scholarly publications in 2021. This report provides an update on volume trends, outcomes, and database initiatives as well as a summary of research productivity resulting from the GTSD over the preceding year.

Tolerability and Feasibility of the Upper Esophageal Sphincter Assist Device in Preventing Acute and Chronic Allograft Rejection Among Lung Transplant Recipients.

GOALS: We aimed to evaluate a novel upper esophageal sphincter (UES) assist device loaner program for the prevention of acute cellular rejection and chronic lung allograft dysfunction among lung transplant (LTx) recipients. BACKGROUND: Laryngopharyngeal reflux can lead to chronic microaspiration and LTx rejection. The UES assist device applies external pressure at the level of UES to decrease reflux. STUDY: We prospectively enrolled and issued UES assist devices to consecutive transplant patients referred for gastrointestinal motility testing from 2016 to 2020. Device tolerability was defined by successful utilization as a bridge to ambulatory pH monitoring and/or antireflux procedure, or as permanent therapy. Incidence of rejection was analyzed before, during, and after device implementation. RESULTS: Twenty-six participants were issued devices (15 pathologic, 5 physiological, 6 unknown reflux status), none of whom developed acute rejection episodes or chronic lung allograft dysfunction while using the device. Thirteen adopted the device promptly after transplantation (mean 1.7 mo) and remained free of rejection episodes over a mean 24.7 months of follow-up. Among those with pathologic reflux, lag time to device adoption strongly correlated with the development of rejection ( r =0.8, P =0.0006). There was no such correlation among those with physiological reflux. Five developed acute rejection after device return. CONCLUSIONS: The device was tolerated by a majority of LTx patients and appears feasible as a barrier measure in the prevention of rejection. Delayed treatment of laryngopharyngeal reflux may lead to early allograft failure; therefore, the UES assist device should be given important consideration in transplant protection.

The Role of Chemotherapy Plus Immune Checkpoint Inhibitors in Oncogenic-Driven NSCLC: A University of California Lung Cancer Consortium Retrospective Study.

Introduction: There is a paucity of data on immune checkpoint inhibitors (ICIs) plus doublet chemotherapy (C) in patients with advanced lung cancer whose tumor harbors an actionable mutation. We sought to provide insight into the role of this combination in relation to chemotherapy alone in this patient population. Methods: We conducted a retrospective study at the five University of California National Cancer Institute-designated Comprehensive Cancer Centers. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and significant adverse events. Adverse events in patients who received a tyrosine kinase inhibitor (TKI) post-ICI were also captured. Results: A total of 246 patients were identified, 170 treated with C plus ICI and 76 treated with C alone. Driver alterations included EGFR (54.9%), KRAS (32.9%), ALK (5.3%), HER2/ERBB2 (2.9%), ROS1 (1.2%), MET (1.2%), RET (0.8%), and BRAF non-V600 (0.8%). The overall PFS and OS hazard ratios were not significant at 1.12 (95% confidence interval 0.83-1.51; p = 0.472) and 0.86 (95% confidence interval: 0.60-1.24, p = 0.429), respectively. No significant differences in PFS or OS were observed in the mutational subgroups. Grade 3 or greater adverse events were lower in the C plus ICI group. The multivariate analysis for PFS and OS revealed a performance status (Eastern Cooperative Oncology Group) score of 2, and previous TKI treatment was associated with poorer outcomes with C plus ICI. Conclusions: Our study suggests that patients with oncogenic-driven NSCLC, primarily those with EGFR-driven tumors, treated with a TKI should not subsequently receive C plus ICI. Analysis from prospective clinical trials will provide additional information on the role of ICIs in this group of patients.

Single-cell chromatin profiling of the primitive gut tube reveals regulatory dynamics underlying lineage fate decisions.

Development of the gastrointestinal system occurs after gut tube closure, guided by spatial and temporal control of gene expression. However, it remains unclear what forces regulate these spatiotemporal gene expression patterns. Here we perform single-cell chromatin profiling of the primitive gut tube to reveal organ-specific chromatin patterns that reflect the anatomical patterns of distinct organs. We generate a comprehensive map of epigenomic changes throughout gut development, demonstrating that dynamic chromatin accessibility patterns associate with lineage-specific transcription factor binding events to regulate organ-specific gene expression. Additionally, we show that loss of Sox2 and Cdx2, foregut and hindgut lineage-specific transcription factors, respectively, leads to fate shifts in epigenomic patterns, linking transcription factor binding, chromatin accessibility, and lineage fate decisions in gut development. Notably, abnormal expression of Sox2 in the pancreas and intestine impairs lineage fate decisions in both development and adult homeostasis. Together, our findings define the chromatin and transcriptional mechanisms of organ identity and lineage plasticity in development and adult homeostasis.

Risk of Acute Lung Injury after Esophagectomy.

To develop a new approach for identifying acute lung injury (ALI) in surgical ward setting and to assess incidence rate, clinical outcomes, and risk factors for ALI cases after esophagectomy. We also compare the degree of lung injury between operative and non-operative sides. Consecutive esophageal cancer patients (n=1022) who underwent esophagectomy from Dec 2012 to Nov 2018 in our hospital were studied. An approach for identifying ALI was proposed that integrated radiographic assessment of lung edema (RALE) score to quantify degree of lung edema. Stepwise logistic regression identified risk factors for postoperative ALI incidence. The degree of bilateral lung injury was compared using the RALE score. The approach for identifying ALI in surgical ward setting was defined as acute onset, PaO2/FiO2≤300 mmHg, bilateral opacities on bedside chest radiograph with a RALE score≥16, and exclusion of cardiogenic pulmonary edema. Incidence rate of ALI was estimated to be 9.7%. ALI diagnosis was associated with multiple clinical complications, prolonged hospital stay, higher medical bills, and higher perioperative mortality. Nine risk factors including BMI, ASA class, DLCO%, duration of surgery, neutrophil percentage, high-density lipoprotein, and electrolyte disorders were identified. The RALE score of the lung lobes of the operative side was higher than the non-operative side. A new approach for identifying ALI in esophageal cancer patients receiving esophagectomy was proposed and several risk factors were identified. ALI is common and has severe outcomes. The lung lobes on the operative side are more likely to be affected than the non-operative side.

Minimally invasive thymectomy for myasthenia gravis favours left-sided approach and low severity class.

OBJECTIVES: Complete thymectomy is a key component of the optimal treatment for myasthenia gravis. Unilateral, minimally invasive approaches are increasingly utilized with debate about the optimal laterality approach. A right-sided approach has a wider field of view, while a left-sided approach accesses potentially more thymic tissue. We aimed to assess the impact of laterality on perioperative and medium-term outcomes, and to identify predictors of a 'good outcome' using standard definitions. METHODS: We performed a multicentre review of 123 patients who underwent a minimally invasive thymectomy for myasthenia gravis between January 2000 and August 2015, with at least 1-year follow-up. The Myasthenia Gravis Foundation of America standards were followed. A 'good outcome' was defined by complete stable remission/pharmacological remission/minimal manifestations 0, and a 'poor outcome' by minimal manifestations 1-3. Univariate and multivariable logistic regression analyses were performed to assess factors associated with a 'good outcome'. RESULTS: Ninety-two percent of thymectomies (113/123) were robotic-assisted. The left-sided approach had a shorter median operating time than a right-sided: 143 (interquartile range, IQR 110-196) vs 184 (IQR 133-228) min, P = 0.012. At a median of 44 (IQR 27-75) months, the left-sided approach achieved a 'good outcome' (46%, 31/68) more frequently than the right-sided (22%, 12/55); P = 0.011. Multivariable analysis identified a left-sided approach and Myasthenia Gravis Foundation of America class I/II to be associated with a 'good outcome'. CONCLUSIONS: A left-sided thymectomy may be preferred over a right-sided approach in patients with myasthenia gravis given the shorter operating times and potential for superior medium-term symptomatic outcomes. A lower severity class is also associated with a 'good outcome'.

Consensus for Thoracoscopic Left Upper Lobectomy-Essential Components and Targets for Simulation.

BACKGROUND: Simulation-based training is a valuable component of cardiothoracic surgical education. Effective curriculum development requires consensus on procedural components and focused attention on specific learning objectives. Through use of a Delphi process, we established consensus on the steps of video-assisted thoracoscopic surgery (VATS) left upper lobectomy and identified targets for simulation. METHODS: Experienced thoracic surgeons were randomly selected for participation. Surgeons voted and commented on the necessity of individual steps comprising VATS left upper lobectomy. Steps with greater than 80% of participants in agreement of their necessity were determined to have established "consensus." Participants voted on the physical or cognitive complexity of each, or both, and chose steps most amenable to focused simulation. RESULTS: Thirty thoracic surgeons responded and joined in the voting process. Twenty operative steps were identified, with surgeons reaching consensus on the necessity of 19. Components deemed most difficult and amenable to simulation included those related to dissection and division of the bronchus, artery, and vein. CONCLUSIONS: Through a Delphi process, surgeons with a variety of practice patterns can achieve consensus on the operative steps of left upper lobectomy and agreement on those most appropriate for simulation. This information can be implemented in the development of targeted simulation for VATS lobectomy.

It's not always too late: a case for minimally invasive salvage esophagectomy.

INTRODUCTION: Standard of care for locally advanced esophageal carcinoma is neoadjuvant chemoradiation (nCRT) and surgical resection 4-8 weeks after completion of nCRT. It is recommended that the CRT to surgery interval not exceed 90 days. Many patients do not undergo surgery within this timeframe due to patient/physician preference, complete clinical response, or poor performance status. Select patients are offered salvage esophagectomy (SE), defined in two ways: resection for recurrent/persistent disease after complete response to definitive CRT (dCRT) or esophagectomy performed > 90 days after completion of nCRT. Salvage esophagectomy reportedly has higher postoperative morbidity and poor survival outcomes. In this study, we assessed outcomes, overall, and disease-free survival of patients undergoing salvage esophagectomy by both definitions (recurrent/persistent disease after dCRT and/or > 90 days), compared to planned (resection after nCRT/within 90 days) esophagectomy (PE). MATERIALS AND METHODS: Retrospective review of a prospectively maintained database identified patients who underwent minimally invasive esophagectomy at a single institution from 2009 to 2019. Esophagectomy for benign disease and patients who did not receive nCRT were excluded. Outcomes included postoperative complications, length of stay (LOS), disease-free survival, and overall survival. RESULTS: 97 patients underwent minimally invasive esophageal resection for esophageal carcinoma. 89.7% of patients were male. Mean age was 64.9 years (range 36-85 years). 94.8% of patients had adenocarcinoma, with 16 transthoracic and 81 transhiatal approaches. On comparing planned esophagectomy (n = 87) to esophagectomy after dCRT failure (n = 10), no significant differences were identified in overall survival (p = 0.73), disease-free survival (p = 0.32), 30-day or major complication rate, anastomotic leak, or LOS. Similarly, when comparing esophagectomy < 90 days after CRT (n = 62) to > 90 days after CRT completion (n = 35), no significant differences were identified in overall survival (p = 0.39), disease-free survival (p = 0.71), 30-day or major complication rate, LOS, or anastomotic leak rate between groups. In this comparison, local recurrence was noted to be elevated with SE as compared to PE (64.3% vs. 25.0%, p = 0.04). CONCLUSION: Overall survival and disease-free survival were equivalent between SE and PE. Local recurrence was noted to be increased with SE, though this did not appear to affect survival. Although planned esophagectomy remains the standard of care, salvage esophagectomy has comparable outcomes and is appropriate for selected patients.

Initial and Longitudinal Cost of Surgical Resection for Lung Cancer.

BACKGROUND: The longitudinal cost of treating patients with non-small cell lung cancer (NSCLC) undergoing surgical resection has not been evaluated. We describe initial and 4-year resource use and cost for NSCLC patients aged 65 years of age or greater who were treated surgically between 2008 and 2013. METHODS: Using clinical data for NSCLC resections from The Society of Thoracic Surgeons General Thoracic Surgery Database linked to Medicare claims, resource use and cost of preoperative staging, surgery, and subsequent care through 4 years were examined ($2017). Cost of hospital-based care was estimated using cost-to-charge ratios; professional services and care in other settings were valued using reimbursements. Inverse probability weighting was used to account for administrative censoring. Outcomes were stratified by pathologic stage and by surgical approach for stage I lobectomy patients. RESULTS: Resection hospitalizations averaged 6 days and cost $31,900. In the first 90 days, costs increased with stage ($12,430 for stage I to $26,350 for stage IV). Costs then declined toward quarterly means more similar among stages. Cumulative costs ranged from $131,032 (stage I) to $205,368 (stage IV). In the stage I lobectomy cohort, patients selected for minimally invasive procedures had lower 4-year costs than did thoracotomy patients ($120,346 versus $136,250). CONCLUSIONS: The 4-year cost of surgical resection for NSCLC was substantial and increased with pathologic stage. Among stage I lobectomy patients, those selected for minimally invasive surgery had lower costs, particularly through 90 days. Potential avenues for improving the value of surgical resection include judicious use of postoperative intensive care and earlier detection and treatment of disease.

Readmission After Lobectomy for Lung Cancer: Not All Complications Contribute Equally.

OBJECTIVE: The aim of this study was to identify independent predictors of hospital readmission for patients undergoing lobectomy for lung cancer. SUMMARY BACKGROUND DATA: Hospital readmission after lobectomy is associated with increased mortality. Greater than 80% of the variability associated with readmission after surgery is at the patient level. This underscores the importance of using a data source that includes detailed clinical information. METHODS: Using the Society of Thoracic Surgeons (STS) General Thoracic Surgery Database (GTSD), we conducted a retrospective cohort study of patients undergoing elective lobectomy for lung cancer. Three separate multivariable logistic regression models were generated: the first included preoperative variables, the second added intraoperative variables, and the third added postoperative variables. The c statistic was calculated for each model. RESULTS: There were 39,734 patients from 277 centers. The 30-day readmission rate was 8.2% (n = 3237). In the final model, postoperative complications had the greatest effect on readmission. Pulmonary embolus {odds ratio [OR] 12.34 [95% confidence interval (CI),7.94-19.18]} and empyema, [OR 11.66 (95% CI, 7.31-18.63)] were associated with the greatest odds of readmission, followed by pleural effusion [OR 7.52 (95% CI, 6.01-9.41)], pneumothorax [OR 5.08 (95% CI, 4.16-6.20)], central neurologic event [OR 3.67 (95% CI, 2.23-6.04)], pneumonia [OR 3.13 (95% CI, 2.43-4.05)], and myocardial infarction [OR 3.16 (95% CI, 1.71-5.82)]. The c statistic for the final model was 0.736. CONCLUSIONS: Complications are the main driver of readmission after lobectomy for lung cancer. The highest risk was related to postoperative events requiring a procedure or medical therapy necessitating inpatient care.

Prior tonsillectomy is associated with an increased risk of esophageal adenocarcinoma.

BACKGROUND: Esophageal cancer is a deadly cancer with 5-year survival <20%. Although multiple risk factors for esophageal adenocarcinoma (EAC) including obesity, GERD and smoking have been identified, these risk factors do not fully explain the rising incidence of EAC. In this study, we evaluated the association between prior history of tonsillectomy and EAC. Our goal was to determine whether tonsillectomies were more frequent in patients with EAC (cases) than in our thoracic surgery controls. METHODS: Cases included 452 esophagectomy cases, including 396 with EAC and 56 who underwent esophagectomy for Barrett's esophagus (BE) with high grade dysplasia (HGD). 1,102 thoracic surgery patients with surgical indications other than dysplastic BE or esophageal cancer represented the controls for our analysis. The association of tonsillectomy and HGD/EAC were primarily evaluated by using univariate tests and then verified by logistic regression analysis. Baseline demographics, medical history, and thoracic surgery controls were compared by using χ2 tests or 95% CIs. Significant risk factors were considered as covariates in the multivariate models while evaluating the association between tonsillectomy and HGD/EAC. P-values or odds ratios were estimated with 95% confidence limits to identify significances which was more appropriate. RESULTS: Tonsillectomy was more common in cases than controls and was found to have a significant association with esophageal cancer (19.9% vs. 12.7%; p-value = 0.0003). This significant association persisted after controlling for other known risk factors/covariates. CONCLUSION: A prior history of tonsillectomy was significantly associated with HGD/EAC and may represent an independent risk factor for the development of EAC. However, the underlying biology driving this association remains unclear.

Equivalent Survival Between Lobectomy and Segmentectomy for Clinical Stage IA Lung Cancer.

BACKGROUND: The oncologic efficacy of segmentectomy is controversial. We compared long-term survival in clinical stage IA (T1N0) Medicare patients undergoing lobectomy and segmentectomy in The Society of Thoracic Surgeons database. METHODS: The Society of Thoracic Surgeons General Thoracic Surgery Database was linked to Medicare data in 14,286 lung cancer patients who underwent segmentectomy (n = 1654) or lobectomy (n = 12,632) for clinical stage IA disease from 2002 to 2015. Cox regression was used to create a long-term survival model. Patients were then propensity matched on demographic and clinical variables to derive matched pairs. RESULTS: In Cox modeling segmentectomy was associated with survival similar to lobectomy in the entire cohort (hazard ratio, 1.04; 95% confidence interval, 0.89-1.20; P = .64) and in the matched subcohort. A subanalysis restricted to the 2009 to 2015 population (n = 11,811), when T1a tumors were specified and positron emission tomography results and mediastinal staging procedures were accurately recorded in the database, also showed that segmentectomy and lobectomy continue to have similar survival (hazard ratio, 1.00; 95% confidence interval, 0.87-1.16). Subanalysis of the pathologic N0 patients demonstrated the same results. CONCLUSIONS: Lobectomy and segmentectomy for early-stage lung cancer are equally effective treatments with similar survival. Surgeons from The Society of Thoracic Surgeons database appear to be selecting patients appropriately for sublobar procedures.

A 37-Year-Old Man With Pleuritic Chest Pain.

CASE PRESENTATION: A 37-year-old man with poorly controlled type 2 diabetes presented with severe right-sided pleuritic chest pain, respiratory splinting, and cough. Two weeks earlier, he had been evaluated at an urgent care for cough and was prescribed a 5-day course of azithromycin for bronchitis. He then presented to our ED reporting mild, right-sided pleuritic chest pain. Vital signs were normal, and his chest radiograph showed a trace right pleural effusion (Fig 1A). He was discharged with naproxen for pleurisy. Three days later, he returned, reporting a dramatic increase in the severity of his pleuritic chest pain and a cough that had become productive of yellow-brown sputum. He denied fever, but endorsed chills and night sweats. His medications included atorvastatin, lisinopril, metformin, and saxagliptin. His parents were from Guam, although he was born and raised in San Diego, CA. He was employed as a social worker and denied any history of cigarette smoking, alcohol, or drug use.

Penetration, Completeness, and Representativeness of The Society of Thoracic Surgeons General Thoracic Surgery Database for Lobectomy.

BACKGROUND: Not all surgeons performing lobectomy in the United States report outcomes to The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD). We examined penetration, completeness, and representativeness of the STS GTSD for lobectomy in the Centers for Medicare and Medicaid Services (CMS) patient population. METHODS: The STS GTSD lobectomies from 2002 to 2013 were linked and matched to CMS data using a deterministic matching algorithm. Penetration at center- and patient-level were determined by the number of CMS lobectomy sites and patients, matched to STS GTSD data, divided by the total number of CMS lobectomy sites and patients, respectively. Completeness was defined as the ratio of lobectomies linked to STS GTSD data to the total number of lobectomies. Representativeness was determined by comparing outcomes for patients undergoing lobectomy at matched and unmatched STS GTSD sites. RESULTS: A total of 9,569 centers were included in the study. Center level penetration steadily increased from 1.2% (10 of 859 sites) in 2002 to 25% (169 of 675 sites) in 2013. Patient-level penetration was highest, 38% (4,177 of 11,018), in 2013. Completeness at GTSD sites varied from 59% to 78% over the study period. Postoperative length of stay was longer for nonparticipants than for STS GTSD surgeons (median 6 versus 5 days, p < 0.001); 30-day mortality was higher for nonparticipants than for STS GTSD participants (3.3% versus 1.6%, p < 0.001). CONCLUSIONS: Participation in the STS GTSD has increased over time, but penetration lags behind that of the other STS National Databases. The STS GTSD participants have superior observed perioperative outcomes for lobectomy compared with nonparticipants. Database participation may reflect high quality care, and ongoing efforts to increase surgeon participation in the STS GTSD should be continued.

Transcriptional signature primes human oral mucosa for rapid wound healing.

Oral mucosal wound healing has long been regarded as an ideal system of wound resolution. However, the intrinsic characteristics that mediate optimal healing at mucosal surfaces are poorly understood, particularly in humans. We present a unique comparative analysis between human oral and cutaneous wound healing using paired and sequential biopsies during the repair process. Using molecular profiling, we determined that wound-activated transcriptional networks are present at basal state in the oral mucosa, priming the epithelium for wound repair. We show that oral mucosal wound-related networks control epithelial cell differentiation and regulate inflammatory responses, highlighting fundamental global mechanisms of repair and inflammatory responses in humans. The paired comparative analysis allowed for the identification of differentially expressed SOX2 (sex-determining region Y-box 2) and PITX1 (paired-like homeodomain 1) transcriptional regulators in oral versus skin keratinocytes, conferring a unique identity to oral keratinocytes. We show that SOX2 and PITX1 transcriptional function has the potential to reprogram skin keratinocytes to increase cell migration and improve wound resolution in vivo. Our data provide insights into therapeutic targeting of chronic and nonhealing wounds based on greater understanding of the biology of healing in human mucosal and cutaneous environments.

Minimally Invasive Lung Cancer Surgery Performed by Thoracic Surgeons as Effective as Thoracotomy.

Purpose The prevalence of minimally invasive lung cancer surgery using video-assisted thoracic surgery (VATS) has increased dramatically over the past decade, yet recent studies have suggested that the lymph node evaluation during VATS lobectomy is inadequate. We hypothesized that the minimally invasive approach to lobectomy for stage I lung cancer resulted in a longitudinal outcome that was not inferior to thoracotomy. Patients and Methods Patients > 65 years of age who had undergone lobectomy for stage I lung cancer between 2002 and 2013 were analyzed within the Society of Thoracic Surgeons General Thoracic Surgery Database, which had been linked to Medicare data, as part of a retrospective-cohort, noninferiority study. Results A total of 10,597 patients with clinical stage I lung cancer who underwent lobectomy were evaluated (4,448 patients underwent thoracotomy, and 6,149 underwent VATS). VATS patients had a more favorable distribution of all health-related variables, including pulmonary function (59% of VATS patients had intact spirometry v 51% of thoracotomy patients; P < .001). Cox proportional hazards models were performed over two eras to account for an evolving practice standard. The mortality risk associated with the VATS approach was not greater than thoracotomy in either the earlier era (2002 to 2008; hazard ratio, 0.97; 95% CI, 0.87 to 1.09; P = .62) or the more recent era (2009 to 2013; hazard ratio, 0.84; 95% CI, 0.75 to 0.93; P < .001). Kaplan-Meier survival estimates of 2,901 propensity-matched VATS-thoracotomy pairs demonstrated that the 4-year survival associated with VATS (68.6%) was modestly superior to thoracotomy (64.8%; P = .003). The analyses detailed above were replicated in a separate cohort of pathologic stage I patients with similar findings. Conclusion The long-term efficacy of lobectomy for stage I lung cancer performed using the VATS approach by board-certified thoracic surgeons does not seem to be inferior to that of thoracotomy.