Bio


Dr. Berry joined the Division of Thoracic Surgery at Stanford in August 2014. He came to Stanford from Duke University, where he had most recently served as Associate Professor. He received his medical degree at the University of Pennsylvania School of Medicine after receiving bachelors and masters degrees in Electrical Engineering at the University of Pennsylvania. He completed his residency in Cardiothoracic Surgery at Duke University Medical Center after performing a residency in General Surgery at the Hospital of the University of Pennsylvania. His Cardiothoracic Surgical training included a year dedicated to Minimally Invasive General Thoracic Surgery, a period that also included an American Association for Thoracic Surgery sponsored Traveling Fellowship at the University of Pittsburgh.

Dr. Berry practices all aspects of thoracic surgery, including procedures for benign and malignant conditions of the lung, esophagus, and mediastinum. He has a particular interest in minimally invasive techniques, and has extensive experience in treating thoracic surgical conditions using video-assisted thoracoscopic surgical (VATS), laparoscopic, robotic, endoscopic, and bronchoscopic approaches. He serves as the co-Director of the Stanford Minimally Invasive Thoracic Surgery Center (SMITS), and has both directed and taught in several minimally invasive thoracic surgery courses.

Dr. Berry also has a Masters of Health Sciences in Clinical Research from Duke University. His clinical research activities mirror his clinical interests and activities in optimizing short-term and long-term outcomes of patients with thoracic surgical conditions. He has more than 150 peer-reviewed publications, most of which are related to both the use of minimally invasive thoracic surgical techniques as well as evaluating outcomes after treatment of thoracic malignancies. His clinical practice and his research both focus on choosing the most appropriate treatment and approach for patients based on the individual characteristics of the patient and their disease process.

Clinical Focus


  • Cancer > Thoracic Oncology
  • Thoracic and Cardiac Surgery

Academic Appointments


Honors & Awards


  • Member, Pi Mu Epsilon National Math Honor Society
  • Member, Eta Kappa Nu National Electrical Engineering Honor Society
  • Member, Tau Beta Pi National Engineering Honor Society
  • Member, Alpha Omega Alpha

Professional Education


  • Board Certification: American Board of Thoracic Surgery, Thoracic and Cardiac Surgery (2010)
  • Residency: Duke University Cardiothoracic Residency (2009) NC
  • Residency: University of Pennsylvania Surgery Residency PA
  • Medical Education: Perelman School of Medicine University of Pennsylvania (1999) PA
  • Board Certification: American Board of Surgery, General Surgery (2007)
  • MHS, Duke University, Clinical Research (2012)
  • MD, University of Pennsylvania, Medicine (1999)
  • Post Bac, University of Pennsylvania, Pre-Health (1994)
  • MSE, University of Pennsylvania, Electrical Engineering (1993)
  • B Eng, University of Pennsylvania, Electrical Engineering (1990)

Clinical Trials


  • Safety and Effectiveness of a New Pleural Catheter for Symptomatic, Recurrent, MPEs Versus Approved Pleural Catheter Not Recruiting

    The purpose of this study is to determine whether a new catheter is safe and effective in treating malignant pleural effusions compared to approve catheter.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

    View full details

Stanford Advisees


All Publications


  • Lepidic-Type Lung Adenocarcinomas: Is It Safe to Observe for Growth Prior to Treating? The Annals of thoracic surgery Wong, L. Y., Elliott, I. A., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2024

    Abstract

    Lepidic-type adenocarcinomas (LPA) can be multi-focal, and treatment is often deferred until there is observed growth. This study investigated the potential downside of that strategy by evaluating the relationship of nodal involvement with tumor size and survival.The impact of tumor size on lymph node involvement and survival was evaluated for National Cancer Database patients who received surgery without induction therapy as primary treatment for cT1-3N0M0 histologically confirmed LPA from 2006-2019 using logistic regression, Kaplan-Meier, and Cox analyses.Positive nodes occurred in 442 (5.3%) of 8,286 patients. The incidence of having positive nodes approximately doubled with each 1cm increment increase in size. Patients with positive nodes were more likely to have larger tumors (27mm vs 20mm,p<0.001) and clinical T2+ disease (40.7% vs 26.8%,p<0.001) compared to node-negative patients, but tumor size was the only significant independent predictor of having positive nodal disease in logistic regression analysis; this association grew stronger with each incremental centimeter increase in size. Patients with positive nodes were more likely to undergo adjuvant radiation (23.5% vs 1.1%,p<0.001) and chemotherapy (72.9% vs 7.9%,p<0.001), and expectedly had worse survival compared to the node negative group in univariate (5-year overall survival 50.9% vs 81.1%,p<0.001) and multivariable (Hazard ratio 2.56 [95% CI 2.14-3.05],p<0.001) analyses.Nodal involvement is relatively uncommon in early-stage LPAs but steadily increases with tumor size and is associated with dramatically worse survival. This data can be used to inform treatment decisions when evaluating LPA patients.

    View details for DOI 10.1016/j.athoracsur.2024.03.003

    View details for PubMedID 38490310

  • Outcomes of surgery for catastrophic hiatal hernia presentations. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Wong, L., Leipzig, M., Elliott, I. A., Liou, D. Z., Backhus, L. M., Shrager, J. B., Berry, M. F. 2024; 28 (3): 285-286

    View details for DOI 10.1016/j.gassur.2023.12.024

    View details for PubMedID 38445922

  • Surgical revision of the postesophagectomy gastric conduit to address poor emptying. JTCVS techniques Wong, L., Rivera, M. F., Liou, D. Z., Berry, M. F. 2024; 23: 132-140

    Abstract

    Introduction: The configuration of the gastric conduit after esophagectomy can lead to chronic gastrointestinal and respiratory issues. Surgical revision of the gastric conduit has been described in small series but appears to be infrequently used. We investigated outcomes of revising dilated or redundant conduit in patients with severe quality-of-life issues.Methods: We identified all patients from 2016 to 2022 at our institution who underwent gastric conduit revision after previous esophagectomy either at our or another institution. Chart review was performed to assess prerevision course and perioperative outcomes. Pre- and postrevision imaging was compared for all patients to assess the impact of surgery on anatomic configuration. Patient-reported gastrointestinal and respiratory issues before and after surgery were examined.Results: The use of right thoracotomy combined with laparotomy to reduce redundancy and improve gastric emptying was performed in 8 patients. The symptoms necessitating reoperation included intolerance to oral intake and poor gastric emptying associated with both acute and chronic aspiration episodes. The median length of stay was 8 [4, 25] days, and there were no perioperative mortalities. Seven (87.5%) patients were tolerating oral intake at discharge. All patients had improvement in their prerevision symptoms on follow-up.Conclusions: Gastric conduit revision can improve severe postesophagectomy gastrointestinal and respiratory symptoms in patients with dilated/redundant conduits with limited perioperative morbidity.

    View details for DOI 10.1016/j.xjtc.2023.11.006

    View details for PubMedID 38351992

  • Commentary: Re-consult surgery for lung cancer patients? The role of resection after initial non-operative therapy. The Journal of thoracic and cardiovascular surgery Lin, N., Berry, M. F. 2024

    View details for DOI 10.1016/j.jtcvs.2024.01.002

    View details for PubMedID 38211895

  • Impact of guideline therapy on survival of patients with stage I-III epithelioid mesothelioma. Journal of thoracic disease Liou, D. Z., Wang, Y., Bhandari, P., Shrager, J. B., Lui, N. S., Backhus, L. M., Berry, M. F. 2023; 15 (12): 6661-6673

    Abstract

    Modern treatment guidelines recommend multimodal therapy with at least chemotherapy and surgery for patients with potentially resectable epithelioid mesothelioma. This study evaluated guideline compliance for patients with stage I-III epithelioid mesothelioma and tested the hypothesis that guideline-concordant therapy improved survival.The National Cancer Database was queried for patients with stage I-III epithelioid malignant pleural mesothelioma between 2004 and 2016. The impact of therapy was evaluated using logistic regression, Kaplan-Meier analysis, Cox-proportional hazards analysis, and propensity-scoring methods.During the study period, guideline-concordant therapy was used in 677 patients (19.1%), and 2,857 patients (80.8%) did not have guideline-concordant therapy. Younger age, being insured, living in a census tract with a higher income, clinical stage, and being treated at an academic or research program were all predictors of receiving guideline-concordant therapy in multivariable analysis. Guideline-concordant therapy yielded improved median survival [24.7 (22.4-26.1) vs. 13.7 (13.2-14.4) months] and 5-year survival [17.7% (14.7-21.3%) vs. 8.0% (7.0-9.3%)] (P<0.001), and continued to be associated with better survival in both multivariable analysis and propensity-matched analysis. In the patients who received guideline therapy, median survival [24.9 (21.9-27.2) vs. 24.5 (21.7-28.1) months] and 5-year survival [14.9% (10.9-20.2%) vs. 20.1% (16.0-25.4%)] was not significantly different between patients who underwent induction (n=304) versus adjuvant (n=373) chemotherapy (P=0.444).Guideline-concordant therapy for potentially resectable epithelioid mesothelioma is associated with significantly improved survival but used in a minority of patients. The timing of chemotherapy with surgery in this study did not have a significant impact on overall survival.

    View details for DOI 10.21037/jtd-23-1334

    View details for PubMedID 38249900

    View details for PubMedCentralID PMC10797401

  • Risk of developing subsequent primary lung cancer after receiving radiation for breast cancer. JTCVS open Wong, L., Kapula, N., He, H., Guenthart, B. A., Vitzthum, L. K., Horst, K., Liou, D. Z., Backhus, L. M., Lui, N. S., Berry, M. F., Shrager, J. B., Elliott, I. A. 2023; 16: 919-928

    Abstract

    Background: Radiotherapy (RT) is integral to breast cancer treatment, especially in the current era that emphasizes breast conservation. The aim of our study was to determine the incidence of subsequent primary lung cancer after RT exposure for breast cancer over a time span of 3decades to quantify this risk over time as modern oncologic treatment continues to evolve.Methods: The SEER (Surveillance, Epidemiology, and End Results) database was queried from 1988 to 2014 for patients diagnosed with nonmetastatic breast cancer. Patients who subsequently developed primary lung cancer were identified. Multivariable regression modeling was performed to identify independent factors associated with the development of lung cancer stratified by follow up intervals of 5 to 9years, 10 to 15years, and >15years after breast cancer diagnosis.Results: Of the 612,746 patients who met our inclusion criteria, 319,014 (52%) were irradiated. primary lung cancer developed in 5556 patients (1.74%) in the RT group versus 4935 patients (1.68%) in the non-RT group. In a multivariable model stratified by follow-up duration, the overall HR of developing subsequent ipsilateral lung cancer in the RT group was 1.14 (P=.036) after 5 to 9years of follow-up, 1.28 (P=.002) after 10 to 15years of follow-up, and 1.30 (P=.014) after >15years of follow-up. The HR of contralateral lung cancer was not increased at any time interval.Conclusions: The increased risk of developing a primary lung cancer secondary to RT exposure for breast cancer is much lower than previously published. Modern RT techniques may have contributed to the improved risk profile, and this updated study is important for counseling and surveillance of breast cancer patients.

    View details for DOI 10.1016/j.xjon.2023.10.031

    View details for PubMedID 38204675

  • Comparison of failure to rescue in younger versus elderly patients following lung cancer resection. JTCVS open Wang, Y., Kapula, N., Yang, C. J., Manapat, P., Elliott, I. A., Guenthart, B. A., Lui, N. S., Backhus, L. M., Berry, M. F., Shrager, J. B., Liou, D. Z. 2023; 16: 855-872

    Abstract

    Objective: Failure to rescue (FTR), defined as in-hospital death following a major complication, has been increasingly studied in patients who undergo cardiothoracic surgery. This study tested the hypothesis that elderly patients undergoing lung cancer resection have greater rates of FTR compared with younger patients.Methods: Patients who underwent surgery for primary lung cancer between 2011 and 2020 and had at least 1 major postoperative complication were identified using the National Surgical Quality Improvement Program database. Patients who died following complications (FTR) were compared with those who survived in an elderly (80+ years) and younger (<80years) cohort.Results: Of the 2823 study patients, the younger cohort comprised 2497 patients (FTR: n=139 [5.6%]), whereas the elderly cohort comprised 326 patients (FTR: n=39 [12.0%]). Pneumonia was the most common complication in younger (877/2497, 35.1%) and elderly patients (118/326, 36.2%) but was not associated with FTR on adjusted analysis. Increasing age was associated with FTR (adjusted odds ratio [AOR], 1.55 per decade, P<.001), whereas unplanned reoperation was associated with reduced risk (AOR, 0.55, P=.01). Within the elderly cohort, surgery conducted by a thoracic surgeon was associated with lower FTR risk (AOR, 0.29, P=.028).Conclusions: FTR following lung cancer resection was more frequent with increasing age. Pneumonia was the most common complication but not a predictor of FTR. Unplanned reoperation was associated with reduced FTR, as was treatment by a thoracic surgeon for elderly patients. Surgical therapy for complications after lung cancer resection and elderly patients managed by a thoracic specialist may mitigate the risk of death following an adverse postoperative event.

    View details for DOI 10.1016/j.xjon.2023.08.002

    View details for PubMedID 38204720

  • The impact of refusing esophagectomy for treatment of locally advanced esophageal adenocarcinoma. JTCVS open Wong, L., Elliott, I. A., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2023; 16: 987-995

    Abstract

    Objective: Patients with esophageal cancer may be reluctant to proceed with surgery due to high complication rates. This study aims to compare outcomes between eligible surgical candidates who proceeded with surgery versus those who refused surgery.Methods: Characteristics and survival of patients with locally advanced (cT3N0M0, cT1-3N+M0) mid-/distal esophageal adenocarcinoma in the National Cancer Database (2006-2019) who either proceeded with or refused surgery after chemoradiotherapy were evaluated with logistic regression, Kaplan-Meier curves, and Cox proportional hazards methods.Results: Of the 13,594 patients included in the analysis, 595 (4.4%) patients refused esophagectomy. Patients who refused surgery were older, had less distance to travel to their treatment facility, were more likely to have cN0 disease, and were more likely to be treated at a community rather than academic or integrated network program, but did not have significantly different comorbid disease distributions. On multivariable analysis, refusing surgery was independently associated with older age, uninsured, lower income, less distance to a hospital, and treatment in a community program versus an academic/research or integrated network program. Esophagectomy was associated with better survival (5-year survival 40.1% [39.2-41] vs 23.6% [19.9-27.9], P<.001) and was also independently associated with better survival in the Cox model (hazard rate, 0.78 [95% confidence interval, 0.7-0.87], P<.001).Conclusions: The results of this study can inform selected patients with resectable esophageal adenocarcinoma that their survival will be significantly diminished if surgery is not pursued. Many factors associated with refusing surgery are non-clinical and suggest that access to or support for care could influence patient decisions.

    View details for DOI 10.1016/j.xjon.2023.09.006

    View details for PubMedID 38204633

  • Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival. Journal of thoracic disease Elliott, I. A., He, H., Lui, N. S., Liou, D. Z., Guenthart, B. A., Shrager, J. B., Berry, M. F., Backhus, L. M. 2023; 15 (11): 6140-6150

    Abstract

    Pleural mesothelioma (PM) is rare but portends a poor prognosis. Multimodal treatment, including aggressive surgical resection, may offer the best chance of treatment response and improved survival. Single-center studies suggest that hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection improves outcomes, but the impact of HITHOC on postoperative morbidity and survival has not been examined on a larger scale.The National Cancer Database was queried for patients undergoing resection for PM from 2006-2017. Patients were excluded if staging or survival data was incomplete. After propensity-score matching, patients who underwent HITHOC were compared to patients who did not (case-control study). Perioperative outcomes and survival were analyzed.The final cohort consisted of 3,232 patients; of these, 365 patients underwent HITHOC. After propensity-score matching, receipt of HITHOC was associated with increased length of stay (12 vs. 7 days, P<0.001) and increased 30-day readmissions (9.9% vs. 4.9%, P=0.007), but decreased 30-day mortality (3.2% vs. 6.0%, P=0.017) and 90-day mortality (7.5% vs. 10.9%). Kaplan-Meier modeling demonstrated that HITHOC was associated with improved survival in the overall cohort (median 20.5 vs. 16.8 months, P=0.001). In multivariable analysis, HITHOC remained associated with improved overall survival [hazard ratio (HR) =0.80; 95% confidence interval (CI): 0.69-0.92; P=0.002], and this persisted in the propensity-matched analysis (HR =0.73; 95% CI: 0.61-0.88; P=0.001).Using a large national database, we describe the impact of HITHOC on survival in patients with PM. Despite observed increased short-term morbidity, in multivariable analysis HITHOC was associated with an overall survival advantage for patients undergoing surgical resection of PM.

    View details for DOI 10.21037/jtd-23-466

    View details for PubMedID 38090290

    View details for PubMedCentralID PMC10713319

  • Impact of hyperthermic intrathoracic chemotherapy (HITHOC) during resection of pleural mesothelioma on patient survival JOURNAL OF THORACIC DISEASE Elliott, I. A., He, H., Lui, N. S., Liou, D. Z., Guenthart, B. A., Shrager, J. B., Berry, M. F., Backhus, L. M. 2023
  • Clinical Impact of EGFR vs KRAS Mutations in Multifocal Lung Adenocarcinoma Jiang, J., Berry, M. F., Lui, N. S., Liou, D. Z., Trope, W. L., Backhus, L. M., Shrager, J. B. ELSEVIER SCIENCE INC. 2023: S484-S485
  • ACR Appropriateness Criteria® Incidentally Detected Indeterminate Pulmonary Nodule. Journal of the American College of Radiology : JACR Martin, M. D., Henry, T. S., Berry, M. F., Johnson, G. B., Kelly, A. M., Ko, J. P., Kuzniewski, C. T., Lee, E., Maldonado, F., Morris, M. F., Munden, R. F., Raptis, C. A., Shim, K., Sirajuddin, A., Small, W., Tong, B. C., Wu, C. C., Donnelly, E. F. 2023; 20 (11S): S455-S470

    Abstract

    Incidental pulmonary nodules are common. Although the majority are benign, most are indeterminate for malignancy when first encountered making their management challenging. CT remains the primary imaging modality to first characterize and follow-up incidental lung nodules. This document reviews available literature on various imaging modalities and summarizes management of indeterminate pulmonary nodules detected incidentally. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

    View details for DOI 10.1016/j.jacr.2023.08.024

    View details for PubMedID 38040464

  • Consequences of a Failed Nonoperative Approach in Paraesophageal Hernia Management ANNALS OF THORACIC SURGERY Wong, L., Berry, M. F. 2023; 116 (4): 860
  • Consequences of a Failed Nonoperative Approach in Paraesophageal Hernia Management ANNALS OF THORACIC SURGERY Wong, L., Berry, M. F. 2023; 116 (4): 860
  • The Role of Salvage Surgery After Definitive Radiation for Non-small-cell Lung Cancer. The Annals of thoracic surgery Rosenstein, A. L., Potter, A. L., Senthil, P., Raman, V., Kumar, A., Muniappan, A., Berry, M., Jeffrey Yang, C. 2023

    Abstract

    BACKGROUND: To evaluate outcomes of patients who undergo extended delay to surgery after definitive radiation for non-small-cell lung cancer (NSCLC).METHODS: Perioperative outcomes and five-year overall survival of patients with NSCLC who underwent definitive radiation followed by surgery from 2004-2020 in the National Cancer Database were evaluated. Patients who underwent surgery >180 days following initiation of radiation therapy (including any external beam therapy at a total dose of >60 g.y) were included in the analysis. Subgroup analyses were conducted by operation type and pathologic nodal status.RESULTS: From 2004-2020, 293 patients had an extended delay to surgery after definitive radiation. The clinical stage distribution was stage I-II in 53 (18.1%), stage IIIA in 111 (37.9%), stage IIIB in 106 (36.2%), stage IIIC in 13 (4.4%), and stage IV in 10 (3.4%) patients. Median dose of radiation received was 64.8 (60.0-66.6) g.y. Median days from radiation to surgery was 221.0 (193.0, 287.0). Lobectomy (64.5%) was the most common operation, followed by pneumonectomy (17.1%) and wedge resection (7.5%). For wedge resection, lobectomy, and pneumonectomy, the thirty-day readmission rate was 4.8%, 4.8%, and 8.3%, the thirty-day mortality rate was 0%, 3.4%, and 6.4%, and the ninety-day mortality rate was 0%, 6.2%, and 12.8% respectively. Five-year overall survival for patients with pN0, pN1, and pN2 disease was 38.6% (95% CI:30.0-47.2), 43.3% (95% CI:16.3-67.9), and 24.0% (95% CI:9.8-41.7), respectively.CONCLUSIONS: In this national analysis, extended delay to surgery after definitive radiation was associated with acceptable perioperative outcomes among a highly selected patient cohort.

    View details for DOI 10.1016/j.athoracsur.2023.07.035

    View details for PubMedID 37544397

  • The impact of neoadjuvant immunotherapy on perioperative outcomes and survival after esophagectomy for esophageal cancer. JTCVS open Wong, L., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2023; 14: 547-560

    Abstract

    Objective: Immunotherapy for esophageal cancer is relatively novel but increasingly used. This study evaluated the early use of immunotherapy as an adjunct to neoadjuvant chemoradiotherapy before esophagectomy for locally advanced disease.Methods: Perioperative morbidity (composite of mortality, hospitalization ≥21days, or readmission) and survival of patients with locally advanced (cT3N0M0, cT1-3N + M0) distal esophageal cancer in the National Cancer Database from 2013 to 2020 who underwent neoadjuvant immunotherapy plus chemoradiotherapy or chemoradiotherapy alone followed by esophagectomy were evaluated using logistic regression, Kaplan-Meier curves, Cox proportional hazards methods, and propensity-matched analysis.Results: Immunotherapy was used in 165 (1.6%) of 10,348 patients. Younger age (odds ratio, 0.66; 95% confidence interval, 0.53-0.81; P<.001) predicted immunotherapy use, which slightly delayed time from diagnosis to surgery versus chemoradiation alone (immunotherapy 148 [interquartile range, 128-177] days vs chemoradiation 138 [interquartile range, 120-162] days, P<.001). There were no statistically significant differences between the immunotherapy and chemoradiation groups for the composite major morbidity index (14.5% [24/165] vs 15.6% [1584/10,183], P=.8). Immunotherapy was associated with a significant improvement in median overall survival (69.1months vs 56.3months, P=.005) and 3-year overall survival in univariate analysis (65.6% [95% confidence interval, 57.7-74.5] vs 55.0% [53.9-56.1], P=.005), and independently predicted improved survival in multivariable analysis (hazard ratio 0.68 [95% confidence interval, 0.52-0.89], P=.006). Propensity-matched analysis also showed that immunotherapy use was not associated with increased surgical morbidity (P=.5) but was associated with improved survival (P=.047).Conclusions: Neoadjuvant immunotherapy use before esophagectomy for locally advanced esophageal cancer did not lead to worse perioperative outcomes and shows promising results on midterm survival.

    View details for DOI 10.1016/j.xjon.2023.03.015

    View details for PubMedID 37425457

  • ASO Visual Abstract: Treatment and Outcomes ofProximal Esophageal Squamous Cell Carcinoma. Annals of surgical oncology Patel, D. C., Yang, C. J., Liou, D. Z., Berry, M. F. 2023

    View details for DOI 10.1245/s10434-023-13628-8

    View details for PubMedID 37219657

  • Characterization of Epidural Analgesia Interruption and Associated Outcomes After Esophagectomy. The Journal of surgical research Byrd, C. T., Kim, R. K., Manapat, P., He, H., Tsui, B. C., Shrager, J. B., Berry, M. F., Backhus, L. M., Lui, N. S., Liou, D. Z. 2023; 290: 92-100

    Abstract

    Interruption of thoracic epidural analgesia may impact the postoperative course following esophagectomy. This study investigates the incidence and causes of epidural interruption in esophagectomy patients along with associated postoperative outcomes.This single-institution retrospective analysis examined patients undergoing esophagectomy who received a thoracic epidural catheter from 2016 to 2020. Patients were stratified according to whether epidural catheter infusion was interrupted or not postoperatively. Outcomes were compared between the two groups, and predictors of epidural interruption and postoperative complications were estimated using multivariable logistic regression.Of the 168 patients who received a thoracic epidural before esophagectomy, 60 (35.7%) required epidural interruption and 108 (64.3%) did not. Interruption commonly occurred on postoperative day 1 and was due to hypotension 80% of the time. Heart failure (10.0% versus 0.9%, P = 0.009), atrial fibrillation (20.0% versus 3.7%, P = 0.002), preoperative opioid use (30.0% versus 16.7%, P = 0.043), and higher American Society of Anesthesiology classification (88.4% versus 70.4%, P = 0.008) were more prevalent in the epidural interruption cohort. The female gender was associated with epidural interruption on multivariable logistic regression (adjusted odds ratio [AOR] 2.45, P = 0.039). Patients in the epidural interruption cohort had a higher incidence of delirium (30.5% versus 13.9%, P = 0.010), sepsis (13.6% versus 3.7%, P = 0.028), and severe anastomotic leak (18.3% versus 7.4%, P = 0.032). On adjusted analysis, heart disease (AOR 4.26, P = 0.027), BMI <18.5 (AOR 9.83, P = 0.031), and epidural interruption due to hypotension (AOR 3.51, P = 0.037) were associated with severe anastomotic leak.Early epidural interruption secondary to hypotension in esophagectomy patients may be a harbinger of postoperative complications such as sepsis and severe anastomotic leak. Patients requiring epidural interruption due to hypotension should have a low threshold for additional workup and early intervention.

    View details for DOI 10.1016/j.jss.2023.04.009

    View details for PubMedID 37224609

  • Surgical Management of Esophageal Perforation: Examining Trends in a Multi-Institutional Cohort. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Wong, L. Y., Leipzig, M., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2023

    Abstract

    Esophageal perforations historically are associated with significant morbidity and mortality and generally require emergent intervention. The influence of improved diagnostic and therapeutic modalities available in recent years on management has not been examined. This study examined the surgical treatments and outcomes of a modern cohort.Patients with esophageal perforation management in the 2005-2020 American College of Surgeons National Surgical Quality Improvement Program database were stratified into three eras (2005-2009, 2010-2014, and 2015-2020). Surgical management was classified as primary repair, resection, diversion, or drainage alone based on procedure codes. The distribution of procedure use, morbidity, and mortality across eras was examined.Surgical management of 378 identified patients was primary repair (n=193,51%), drainage (n=89,24%), resection (n=70,18%), and diversion (n=26,7%). Thirty-day mortality in the cohort was 9.5% (n=36/378) and 268 patients (71%) had at least one complication. The median length of stay was 15 days. Both morbidity (Era 1 65% [n=42/60] versus Era 2 69% [n=92/131] versus Era 3 72% [n=135/187], p=0.3) and mortality (Era 1 11% [n=7/65] versus Era 2 9% [n=12/131] versus Era 3 10% [n=19/187], p=0.9) did not change significantly over the three defined eras. Treatment over time evolved such that primary repair was more frequently utilized (43% in Era 1 to 51% in Era 3) while diversion was less often performed (13% in Era 1 to 7% in Era 3) (p=0.009).Esophageal perforation management in recent years uses diversion less often but remains associated with significant morbidity and mortality.

    View details for DOI 10.1007/s11605-023-05700-1

    View details for PubMedID 37165161

    View details for PubMedCentralID 7330325

  • Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO/ESTRO Clinical Practice Guideline. Practical radiation oncology Iyengar, P., All, S., Berry, M. F., Boike, T. P., Bradfield, L., Dingemans, A. C., Feldman, J., Gomez, D. R., Hesketh, P. J., Jabbour, S. K., Jeter, M., Josipovic, M., Lievens, Y., McDonald, F., Perez, B. A., Ricardi, U., Ruffini, E., De Ruysscher, D., Saeed, H., Schneider, B. J., Senan, S., Widder, J., Guckenberger, M. 2023

    Abstract

    This joint guideline by American Society for Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) was initiated to review evidence and provide recommendations regarding the use of local therapy in the management of extracranial oligometastatic non-small cell lung cancer (NSCLC). Local therapy is defined as the comprehensive treatment of all known cancer-primary tumor, regional nodal metastases, and metastases-with definitive intent.ASTRO and ESTRO convened a task force to address 5 key questions focused on the use of local (radiation, surgery, other ablative methods) and systemic therapy in the management of oligometastatic NSCLC. The questions address clinical scenarios for using local therapy, sequencing and timing when integrating local with systemic therapies, radiation techniques critical for oligometastatic disease targeting and treatment delivery, and the role of local therapy for oligoprogression or recurrent disease. Recommendations were based on a systematic literature review and created using ASTRO guidelines methodology.Based on the lack of significant randomized phase 3 trials, a patient-centered, multidisciplinary approach was strongly recommended for all decision-making regarding potential treatment. Integration of definitive local therapy was only relevant if technically feasible and clinically safe to all disease sites, defined as 5 or fewer distinct sites. Conditional recommendations were given for definitive local therapies in synchronous, metachronous, oligopersistent, and oligoprogressive conditions for extracranial disease. Radiation and surgery were the only primary definitive local therapy modalities recommended for use in the management of patients with oligometastatic disease, with indications provided for choosing one over the other. Sequencing recommendations were provided for systemic and local therapy integration. Finally, multiple recommendations were provided for the optimal technical use of hypofractionated radiation or stereotactic body radiation therapy as definitive local therapy, including dose and fractionation.Presently, data regarding clinical benefits of local therapy on overall and other survival outcomes is still sparse for oligometastatic NSCLC. However, with rapidly evolving data being generated supporting local therapy in oligometastatic NSCLC, this guideline attempted to frame recommendations as a function of the quality of data available to make decisions in a multidisciplinary approach incorporating patient goals and tolerances.

    View details for DOI 10.1016/j.prro.2023.04.004

    View details for PubMedID 37294262

  • Consequences of a Failed Nonoperative Approach in Paraesophageal Hernia Management. The Annals of thoracic surgery Wong, L. Y., Berry, M. F. 2023

    View details for DOI 10.1016/j.athoracsur.2023.03.020

    View details for PubMedID 36963646

  • ASO Visual Abstract: Impact of Delaying Surgery After Chemoradiation on Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma. Annals of surgical oncology Wong, L. Y., Liou, D. Z., Vitzthum, L. K., Backhus, L. M., Lui, N. S., Chang, D., Shrager, J. B., Berry, M. F. 2023

    View details for DOI 10.1245/s10434-023-13156-5

    View details for PubMedID 36759429

  • The Impact of Age and Need for Emergent Surgery in Paraesophageal Hernia Repair Outcomes. The Annals of thoracic surgery Wong, L. Y., Parsons, N., David, E. A., Burfeind, W., Berry, M. F. 2023

    Abstract

    Observation of paraesophageal hernias (PEH) may lead to emergent surgery for hernia-related complications. This study evaluated urgent/emergent repair outcomes to quantify the possible sequelae of failed conservative PEH management.The impact of operative status (Elective vs. Urgent/Emergent) on perioperative mortality or major morbidity for patients who underwent hiatal hernia repair for a paraesophageal hernia diagnosis from 2012-2021 in the Society of Thoracic Surgery General Thoracic Surgery Database was evaluated with multivariable logistic regression models.Overall, 2,082 (10.9%) of 19,122 PEH patients underwent Urgent/Emergent repair. Non-elective surgery patients were significantly older than elective surgery patients (median age 73 years [IQR 63-82] versus 66 [58-74]) and had a lower preoperative performance score (p<0.001). Non-elective surgeries were more likely to be done through the chest or via laparotomy rather than via laparoscopy (20% versus 11.4%, p<0.001) and were associated with longer hospitalizations (4 days vs 2, p<0.001), higher operative mortality (4.5% vs 0.6%, p<0.001), and higher major morbidity (27% versus 5.5%, p<0.001). Non-elective surgery was a significant independent predictor of major morbidity in multivariable analysis (odds ratio 2.06, p<0.001). Patients over the age of 80 had higher operative mortality (4.3% vs 0.6%, p<0.001) and major morbidity (19% vs 6.1%, p<0.001) than younger patients overall, and more often had non-elective surgery (26% vs 8.6%, p<0.001) CONCLUSIONS: The operative morbidity of PEH repair is significantly increased when surgery is non-elective, particularly for older patients. These results can inform the potential consequences of choosing watchful waiting versus elective PEH repair.

    View details for DOI 10.1016/j.athoracsur.2023.01.017

    View details for PubMedID 36702291

  • ASO Author Reflections: Timing of Surgery and Chemoradiation for Esophageal Squamous Cell Carcinoma. Annals of surgical oncology Wong, L., Berry, M. F. 2023

    View details for DOI 10.1245/s10434-022-13048-0

    View details for PubMedID 36607525

  • Does delaying surgery following induction chemotherapy compromise survival in patients with mesothelioma? JOURNAL OF CANCER METASTASIS AND TREATMENT Wong, L., Baiu, I., Leipzig, M., Titan, A., Liou, D. Z., Lui, N., Berry, M., Shrager, J. B., Backhus, L. 2023; 9
  • Impact of Delaying Surgery After Chemoradiation on Outcomes for Locally Advanced Esophageal Squamous Cell Carcinoma. Annals of surgical oncology Wong, L., Liou, D. Z., Vitzthum, L. K., Backhus, L. M., Lui, N. S., Chang, D., Shrager, J. B., Berry, M. F. 2022

    Abstract

    BACKGROUND: Performing selective esophagectomy for locally advanced squamous cell carcinoma may spare patients morbidity, but delayed surgery may infer higher risks. This study evaluated the impact of length of time between chemoradiation and esophagectomy on perioperative outcomes and long-term survival.METHODS: The impact of surgical timing, stratified by surgery performed < 180 and ≥ 180 days from starting radiation, on perioperative outcomes and survival in patients treated with chemoradiation and esophagectomy for cT1N + M0 and cT2-4, any N, M0 squamous cell carcinoma of the mid-distal esophagus in the National Cancer Database (2006-2016) was evaluated with logistic regression, Kaplan-Meier curves, Cox proportional-hazards methods, and propensity-matched analysis.RESULTS: Median time between starting radiation and esophagectomy in 1641 patients was 93 (IQR 81-114) days. Most patients (96.8%, n = 1589) had surgery within 180 days of starting radiation, while 52 patients (3.2%) had delayed surgery. Black race and clinical T stage were associated with delayed surgery. Rates of pathologic upstaging, downstaging, complete response, and positive margins were not significantly different between the groups. Patients with delayed surgery had increased major morbidity as measured by a composite of length of hospital stay, readmission, and 30-day mortality [42.3% (22/52) vs 22.3% (355/1589), p = 0.001]. However, delayed surgery was not associated with a significant difference in survival in both univariate [5-year survival 32.8% (95% CI 21.1-50.7) vs 47.3% (44.7-50.1), p = 0.19] and multivariable analysis [hazard ratio (HR) 1.23 (0.85-1.78), p = 0.26].CONCLUSIONS: Delaying surgery longer than 180 days after starting chemoradiation for esophageal squamous cell carcinoma is associated with worse perioperative outcomes but not long-term survival.

    View details for DOI 10.1245/s10434-022-12980-5

    View details for PubMedID 36572807

  • An Investigation of Cancer-Directed Surgery for Different Histologic Subtypes of Malignant Pleural Mesothelioma. Chest Mansur, A., Potter, A., Zurovec, A. J., Nathamuni, K. V., Meyerhoff, R. R., Berry, M. F., Kang, A., Jeffrey Yang, C. 2022

    Abstract

    BACKGROUND: The role of cancer-directed surgery in the treatment of stage I-IIIA malignant pleural mesothelioma (MPM) by histologic subtypes remains controversial. The objective of this study was to evaluate the survival of the different histologic subtypes for stage I-IIIA MPM stratified by cancer-directed surgery and nonoperative management.RESEARCH QUESTION: How is the histologic subtype, clinical stage, and use of cancer-directed surgery with MPM associated with overall survival?STUDY DESIGN AND METHODS: Overall survival of patients with stage I-IIIA epithelioid, sarcomatoid, and biphasic MPM in the National Cancer Database from 2004-2017 who underwent cancer-directed surgery (i.e., surgery with or without chemotherapy + radiation) or chemotherapy with or without radiation ('nonoperative management') was evaluated using KaplanMeier analysis, multivariable Cox proportional hazards analysis, and propensity score-matched analysis.RESULTS: Of 2,285 patients with stage I-IIIA MPM who met inclusion criteria, histologic subtype was epithelioid in 71% of patients, sarcomatoid in 12% of patients, and biphasic in 17% of patients. Median survival was 20 months in the epithelioid group, 8 months in the sarcomatoid group, and 13 months in the biphasic group (P < 0.01). Among patients who underwent surgery, median survival was 25 months in the epithelioid group, 8 months in the sarcomatoid group, and 15 months in the biphasic group (P < 0.01). In multivariable Cox proportional hazards analyses, surgery was associated with improved survival in the epithelioid group (P < 0.01) but not in the sarcomatoid (P = 0.63) or biphasic (P = 0.21) groups. These findings were consistent in propensity score-matched analyses for each MPM histology.INTERPRETATION: In this national analysis, cancer-directed surgery was found to be associated with improved survival for stage I-IIIA epithelioid MPM but not for biphasic or sarcomatoid MPM.

    View details for DOI 10.1016/j.chest.2022.12.019

    View details for PubMedID 36574925

  • Risk of adenocarcinoma in patients with a suspicious ground-glass opacity: a retrospective review. Journal of thoracic disease Roy, E., Shrager, J., Benson, J., Trope, W. L., Bhandari, P., Lui, N., Liou, D., Backhus, L., Berry, M. F. 2022; 14 (11): 4236-4245

    Abstract

    Both primary lung adenocarcinoma and benign processes can have a ground-glass opacity (GGO) appearance on imaging. This study evaluated the incidence of and risk factors for malignancy in a diverse cohort of patients who underwent resection of a GGO suspicious for lung cancer.All patients who underwent resection of a pulmonary nodule with a GGO component and suspected to be primary lung cancer at a single institution from 2001-2017 were retrospectively reviewed. Risk factors for malignancy were evaluated using multivariable logistic regression analysis that included nodule size, age, sex, and race as potential predictors.The incidence of pulmonary adenocarcinoma in the 243 patients who met inclusion criteria was 86% (n=208). The most common pathologic findings in 35 patients with a benign pathology was granulomatous inflammation (n=14, 40%). Risk factors for adenocarcinoma in multivariable logistic regression were age [odds ratio (OR) 1.06, P=0.003], GGO size (OR 2.76, P<0.001), female sex (OR 4.47, P=0.002), and Asian race (OR 8.35, P=0.002). In this cohort, adenocarcinoma was found in 100% (44/44) of Asian females, 86% (25/29) of Asian males, 84% (98/117) of non-Asian females, and 77% (41/53) of non-Asian males.The likelihood of adenocarcinoma in lung nodules with a ground-glass component is influenced by sex and race. Asian females with a GGO have a much higher likelihood of having adenocarcinoma than men and non-Asians. This data can be used when deciding whether to pursue nodule resection or surveillance in a patient with a GGO.

    View details for DOI 10.21037/jtd-22-583

    View details for PubMedID 36524073

    View details for PubMedCentralID PMC9745528

  • Treatment and Outcomes of Proximal Esophageal Squamous Cell Carcinoma. Annals of surgical oncology Patel, D. C., Yang, C. J., Liou, D. Z., Berry, M. F. 2022

    Abstract

    INTRODUCTION: This study evaluated the treatment of proximal (cervical or upper thoracic) esophageal squamous cell carcinoma (SCC), for which chemoradiation is the recommended therapy.METHODS: Treatment and outcomes of patients with cT1-3N0-1M0 proximal esophageal SCC in the National Cancer Database between 2004 and 2016 was evaluated using logistic regression, Kaplan-Meier analysis, and propensity-score matching.RESULTS: Therapy of 2159 patients was chemoradiation (n=1500, 69.5%), no treatment (n=205, 9.5%), surgery (n=203, 9.4%), radiation alone (n=190, 8.8%), and chemotherapy alone (n=61, 2.8%). Factors associated with definitive therapy with either chemoradiation or surgery were younger age, non-Black race, being insured, cervical tumor location, clinical T2 and T3 stage, clinical nodal involvement, and treatment at a research/academic program. Five-year survival was significantly better in patients treated with definitive therapy than patients not treated definitively (34.0% vs. 13.3%, p<0.001). In multivariable survival analysis, receiving definitive therapy (hazard ratio [HR] 0.39, p=0.017) was associated with improved survival, while increasing age, male sex, clinical T3 stage, positive clinical nodal involvement, and increasing Charlson Comorbidity Index were associated with worse survival. Esophagectomy was not associated with improved survival in multivariable analysis of the definitive therapy cohort (HR 0.84, p=0.08) or propensity matched analysis. However, the pathologic complete response was only 33.3% (40/120) for patients who did have an esophagectomy after chemoradiation.CONCLUSIONS: This national analysis supports definitive chemoradiation for not only cervical but also proximal thoracic esophageal SCC. Routine surgery does not appear to be necessary but may have a role in patients with residual disease after chemoradiation.

    View details for DOI 10.1245/s10434-022-12683-x

    View details for PubMedID 36305985

  • Lobar versus sublobar resection in clinical stage IA primary lung cancer with occult N2 disease. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Liou, D. Z., Chan, M., Bhandari, P., Lui, N. S., Backhus, L. M., Shrager, J. B., Berry, M. F. 2022

    Abstract

    Sublobar resection is increasingly being utilized for early-stage lung cancers, but optimal management when final pathology shows unsuspected mediastinal nodal disease is unclear. This study tested the hypothesis that lobectomy has improved survival compared to sublobar resection for clinical stage IA tumors with occult N2 disease.The use of sublobar resection and lobectomy for patients in the National Cancer Database who underwent primary surgical resection for clinical stage IA non-small cell lung cancer with pathologic N2 disease between 2010 and 2017 was evaluated using logistic regression. Survival was assessed with Kaplan-Meier analysis, log-rank test, and Cox proportional hazards model.A total of 2,419 patients comprised the study cohort, including 320 sublobar resections (13.2%) and 2,099 lobectomies (86.8%). Older age, female sex, smaller tumour size, and treatment at an academic facility predicted the use of sublobar resection. Patients undergoing lobectomy had larger tumors (2.40 vs 2.05 cm, p < 0.001) and more lymph nodes examined (11 vs 5, p < 0.001). Adjuvant chemotherapy use was similar between the two groups (sublobar 79.4% vs lobectomy 77.4%, p = 0.434). Sublobar resection was not associated with worse survival compared to lobectomy in both univariate (5-year survival 46.6% vs 45.2%, p = 0.319) and multivariable Cox proportional hazards analysis (HR 0.97, p = 0.789).Clinical stage IA non-small cell lung cancer patients with N2 disease on final pathology have similar long-term survival with either sublobar resection or lobectomy. Patients with occult N2 disease after sublobar resection may not require reoperation for completion lobectomy but should instead proceed to adjuvant chemotherapy.

    View details for DOI 10.1093/ejcts/ezac440

    View details for PubMedID 36063054

  • Risk of adenocarcinoma in patients with a suspicious ground-glass opacity: a retrospective review JOURNAL OF THORACIC DISEASE Roy, E., Shrager, J., Benson, J., Trope, W., Bhandari, P., Lui, N., Liou, D., Backhus, L., Berry, M. F. 2022
  • Eligibility for Lung Cancer Screening Among Women Receiving Screening for Breast Cancer. JAMA network open Titan, A. L., Baiu, I., Liou, D., Lui, N. S., Berry, M., Shrager, J., Backhus, L. 2022; 5 (9): e2233840

    View details for DOI 10.1001/jamanetworkopen.2022.33840

    View details for PubMedID 36178692

  • Treatment for Early-Stage Lung Cancer Should Never Be "Just a Wedge" COMMENT ANNALS OF THORACIC SURGERY Berry, M. F. 2022; 114 (3): 997-998
  • Genomic Profiling of Bronchoalveolar Lavage Fluid in Lung Cancer. Cancer research Nair, V. S., Hui, A. B., Chabon, J. J., Shahrokh Esfahani, M., Stehr, H., Nabet, B. Y., Zhou, L., Chaudhuri, A. A., Benson, J. A., Ayers, K., Bedi, H., Ramsey, M. C., Van Wert, R., Antic, S., Lui, N. S., Backhus, L. M., Berry, M. F., Sung, A. W., Massion, P. P., Shrager, J. B., Alizadeh, A. A., Diehn, M. 2022

    Abstract

    Genomic profiling of Bronchoalveolar Lavage (BAL) samples may be useful for tumor profiling and diagnosis in the clinic. Here, we compared tumor-derived mutations detected in BAL samples from subjects with non-small cell lung cancer (NSCLC) to those detected in matched plasma samples. CAncer Personalized Profiling by deep Sequencing (CAPP-Seq) was used to genotype DNA purified from BAL, plasma and tumor samples from patients with NSCLC. The characteristics of cell-free DNA (cfDNA) isolated from BAL fluid were first characterized to optimize the technical approach. Somatic mutations identified in tumor were then compared to those identified in BAL and plasma, and the potential of BAL cfDNA analysis to distinguish lung cancer patients from risk-matched controls was explored. In total, 200 biofluid and tumor samples from 38 cases and 21 controls undergoing BAL for lung cancer evaluation were profiled. More tumor variants were identified in BAL cfDNA than plasma cfDNA in all stages (p<0.001) and in stage I-II disease only. Four of 21 controls harbored low levels of cancer-associated driver mutations in BAL cfDNA (mean VAF=0.5%), suggesting the presence of somatic mutations in non-malignant airway cells. Finally, using a Random Forest model with leave-one-out cross validation, an exploratory BAL genomic classifier identified lung cancer with 69% sensitivity and 100% specificity in this cohort and detected more cancers than BAL cytology. Detecting tumor-derived mutations by targeted sequencing of BAL cfDNA is technically feasible and appears to be more sensitive than plasma profiling. Further studies are required to define optimal diagnostic applications and clinical utility.

    View details for DOI 10.1158/0008-5472.CAN-22-0554

    View details for PubMedID 35748739

  • Half of Anastomotic Leaks after Esophagectomy are Undetected on Initial Postoperative Esophagram. The Annals of thoracic surgery Elliott, I. A., Berry, M. F., Trope, W., Lui, N. S., Guenthart, B. A., Liou, D. Z., Whyte, R. I., Backhus, L. M., Shrager, J. B. 2022

    Abstract

    The sensitivity of fluoroscopic esophagrams with oral contrast to exclude anastomotic leak after esophagectomy is not well-documented, and the consequences of missing a leak in this setting have not been previously described.We performed a retrospective cohort study of a prospectively maintained institutional database of patients undergoing esophagectomy with esophagogastric anastomosis 2008-2020. Relevant details regarding leaks, management, and outcomes were obtained from the database and formal chart review. Statistical analysis was performed to compare patients with and without leaks, and those with false negative versus positive esophagrams.There were 384 patients who underwent esophagectomy with gastric reconstruction: the majority were Ivor-Lewis (82%), and 51% were wholly or partially minimally-invasive. Using a broad definition of leak, 55 patients (16.7%) developed an anastomotic leak. Twenty-seven of the 55 patients (49%) who ultimately were found to have a leak initially had a negative esophagram (performed on average on postoperative day 6). Those with a negative initial esophagram were more likely to have an uncontained leak (81% vs. 29%, p<0.01), require unplanned readmission (70% vs. 39%, p=0.02), and undergo reoperation (44% vs. 11%, p<0.01).Early postoperative esophagrams intended to evaluate anastomotic integrity have a low sensitivity of 51%, and leaks missed on initial esophagram have greater clinical consequences than those identified on initial esophagram. These findings suggest a high index of suspicion must be maintained even after a normal esophagram and calls into question the common practice of using this test to triage patients for diet advancement.

    View details for DOI 10.1016/j.athoracsur.2022.04.053

    View details for PubMedID 35618049

  • Positron emission tomography/computed tomography differentiates resectable thymoma from anterior mediastinal lymphoma. The Journal of thoracic and cardiovascular surgery Byrd, C. T., Trope, W. L., Bhandari, P., Konsker, H. B., Moradi, F., Lui, N. S., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B. 2022

    Abstract

    OBJECTIVE: Discrete anterior mediastinal masses most often represent thymoma or lymphoma. Lymphoma treatment is nonsurgical and requires biopsy. Noninvasive thymoma is ideally resected without biopsy, which may potentiate pleural metastases. This study sought to determine if clinical criteria or positron emission tomography/computed tomography could accurately differentiate the 2, guiding a direct surgery versus biopsy decision.METHODS: A total of 48 subjects with resectable thymoma and 29 subjects with anterior mediastinal lymphoma treated from 2006 to 2019 were retrospectively examined. All had pretreatment positron emission tomography/computed tomography and appeared resectable (solitary, without clear invasion or metastasis). Reliability of clinical criteria (age and B symptoms) and positron emission tomography/computed tomography maximum standardized uptake value were assessed in differentiating thymoma and lymphoma using Wilcoxon rank-sum test, chi-square test, and logistic regression. Receiver operating characteristic analysis identified the maximum standardized uptake value threshold most associated with thymoma.RESULTS: There was no association between tumor type and age group (P=.183) between those with thymoma versus anterior mediastinal lymphoma. Patients with thymoma were less likely to report B symptoms (P<.001). The median maximum standardized uptake value of thymoma and lymphoma differed dramatically: 4.35 versus 18.00 (P<.001). Maximum standardized uptake value was independently associated with tumor type on multivariable regression. On receiver operating characteristic analysis, lower maximum standardized uptake value was associated with thymoma. Maximum standardized uptake value less than 12.85 was associated with thymoma with 100.00% sensitivity and 88.89% positive predictive value. Maximum standardized uptake value less than 7.50 demonstrated 100.00% positive predictive value for thymoma.CONCLUSIONS: Positron emission tomography/computed tomography maximum standardized uptake value of resectable anterior mediastinal masses may help guide a direct surgery versus biopsy decision. Tumors with maximum standardized uptake value less than 7.50 are likely thymoma and thus perhaps appropriately resected without biopsy. Tumors with maximum standardized uptake value greater than 7.50 should be biopsied to rule out lymphoma. Lymphoma is likely with maximum standardized uptake value greater than 12.85.

    View details for DOI 10.1016/j.jtcvs.2022.02.055

    View details for PubMedID 35568521

  • Silver Nitrate-Coated Versus Standard Indwelling Pleural Catheter for Malignant Effusions: The SWIFT Randomized Trial. Annals of the American Thoracic Society Shrager, J. B., Bhatnagar, R., Kearney, C. T., Retzlaff, N. P., Cohen, E., Stanton, A. E., Keyes, C., Wahidi, M. M., Gillespie, C., Rahman, N., Kerry, A. L., Feller-Kopman, D., Nader, D., Akulian, J., Chen, A., Berry, M., Majid, A., Reddy, C., Tremblay, A., Maskell, N. A. 2022

    Abstract

    RATIONALE: Tunneled, indwelling pleural catheters (IPC) have been demonstrated to be an effective method of managing malignant pleural effusions. However, they allow pleurodesis and can therefore be removed in only a subset of patients. A novel, silver-nitrate coated IPC was developed with the intention of creating a rapid, effective chemical pleurodesis to allow more frequent and earlier catheter removal. This study represent the pivotal clinical trial evaluating that catheter vs the standard IPC.OBJECTIVES: To compare the efficacy of a novel silver nitrate-eluting indwelling pleural catheter (SNCIPC) with that of a standard, uncoated catheter.METHODS: The SWIFT trial was a multicentre, parallel-group, randomised, controlled, patient-blind trial. Central randomisation occurred following a computer-generated schedule, stratified by site. Recruitment was from 17 secondary or tertiary-care hospitals in the USA and 3 in the UK and included adult patients with malignant pleural effusion needing drainage, without evidence of lung entrapment or significant loculation. The intervention group underwent insertion of a SNCIPC with maximal fluid drainage, followed by a tapering drainage schedule. The control group received a standard, uncoated catheter. Follow up was until 90 days. The primary outcome measure was pleurodesis efficacy, measured by fluid drainage, at 30 days.RESULTS: 119 patients were randomised. 5 withdrew before receiving treatment, leaving 114 (77 SNCIPC, 37 standard IPC) for intention-to-treat analysis. Mean age was 66 years (SD 11). More patients in the SNCIPC group were in-patients (39% vs 14%, p=0.009). For the primary outcome, pleurodesis rates were 12/37 (32%) in the control group and 17/77 (22%) in the SNCIPC group (rate difference -0.10, 95% CI -0.30-0.09). Median time to pleurodesis was 11 days (IQR 9-23) in the control group and 4 days (IQR 2-15) in the SNCIPC group. No significant difference in treatment-related adverse event rates was noted between groups.CONCLUSIONS: The SNCIPC did not improve pleurodesis efficacy compared to a standard indwelling pleural catheter. This study does not support the wider use of the SNCIPC device. Clinical trial registered with ClinicalTrials.gov (NCT02649894).

    View details for DOI 10.1513/AnnalsATS.202111-1301OC

    View details for PubMedID 35363591

  • Consensus for Thoracoscopic Lower Lobectomy: Essential Components and Targets for Simulation. The Annals of thoracic surgery Erwin, P. A., Lee, A. C., Ahmad, U., Antonoff, M., Arndt, A., Backhus, L., Berry, M., Birdas, T., Cassivi, S. D., Chang, A. C., Cooke, D. T., Crabtree, T., DeCamp, M., Donington, J., Fernandez, F., Force, S., Gaissert, H., Hofstetter, W., Huang, J., Kent, M., Kim, A. W., Lin, J., Martin, L. W., Meyerson, S., Mitchell, J. D., Molena, D., Odell, D., Onaitis, M., Puri, V., Putnam, J., Reddy, R., Schipper, P., Seder, C. W., Shrager, J., Tong, B., Veeramachaneni, N., Watson, T., Whyte, R., Ferguson, M. K. 2021

    Abstract

    BACKGROUND: Despite demonstration of its clear benefits relative to open approaches, a video-assisted thoracic surgery (VATS) technique for pulmonary lobectomy has not been universally adopted. This study aims to overcome potential barriers by establishing the essential components of the operation as well as determining which steps would be most useful for simulation training.METHODS: After randomly selecting experienced thoracic surgeons to participate, an initial list of components to a lower lobectomy was distributed. Feedback was provided by the participants and modifications were made based on anonymous responses in a Delphi process. Components were declared essential once at least 80% of participants came to an agreement. The steps were then rated based upon cognitive and technical difficulty, followed by listing the components most appropriate for simulation.RESULTS: After three rounds of voting, 18 components were identified as essential to performance of a VATS lower lobectomy. The components deemed the most difficult included isolation and division of the basilar and superior segmental branches of the pulmonary artery, isolation and division of the lower lobe bronchus, and the dissection of lymphovascular tissue to expose the target bronchus. The steps determined to be most amenable for simulation included isolation and division of the branches of the pulmonary artery, the lower lobe bronchus, and the inferior pulmonary vein.CONCLUSIONS: Using a Delphi process, a list of essential components for a VATS lower lobectomy was established. Furthermore, three components were identified as most appropriate for simulation-based training, providing insights for future simulation development.

    View details for DOI 10.1016/j.athoracsur.2021.09.033

    View details for PubMedID 34688617

  • Rationale and design of a mechanistic clinical trial of JAK inhibition to prevent ventilator-induced diaphragm dysfunction. Respiratory medicine Shrager, J. B., Wang, Y., Lee, M., Nesbit, S., Trope, W., Konsker, H., Fatodu, E., Berry, M. S., Poulstides, G., Norton, J., Burdon, T., Backhus, L., Cooke, R., Tang, H. 2021; 189: 106620

    Abstract

    INTRODUCTION: Ventilator-induced diaphragm dysfunction (VIDD) is an important phenomenon that has been repeatedly demonstrated in experimental and clinical models of mechanical ventilation. Even a few hours of MV initiates signaling cascades that result in, first, reduced specific force, and later, atrophy of diaphragm muscle fibers. This severe, progressive weakness of the critical ventilatory muscle results in increased duration of MV and thus increased MV-associated complications/deaths. A drug that could prevent VIDD would likely have a major positive impact on intensive care unit outcomes. We identified the JAK/STAT pathway as important in VIDD and then demonstrated that JAK inhibition prevents VIDD in rats. We subsequently developed a clinical model of VIDD demonstrating reduced contractile force of isolated diaphragm fibers harvested after 7 vs 1h of MV during a thoracic surgical procedure.MATERIALS AND METHODS: The NIH-funded clinical trial that has been initiated is a prospective, placebo controlled trial: subjects undergoing esophagectomy are randomized to receive 6 preoperative doses of the FDA-approved JAK inhibitor Tofacitinib (commonly used for rheumatoid arthritis) vs. placebo. The primary outcome variable will be the difference in the reduction that occurs in force generation of diaphragm single muscle fibers (normalized to their cross-sectional area), in the Tofacitinib vs. placebo subjects, over 6h of MV.DISCUSSION: This trial represents a first-in-human, mechanistic clinical trial of a drug to prevent VIDD. It will provide proof-of-concept in human subjects whether JAK inhibition prevents clinical VIDD, and if successful, will support an ICU-based clinical trial that would determine whether JAK inhibition impacts clinical outcome variables such as duration of MV and mortality.

    View details for DOI 10.1016/j.rmed.2021.106620

    View details for PubMedID 34655959

  • Induction therapy is not associated with improved survival in large cT4N0 non-small cell lung cancers. The Annals of thoracic surgery Sun, B. J., Bhandari, P., Jeffrey Yang, C., Berry, M. F., Shrager, J. B., Backhus, L. M., Lui, N. S., Liou, D. Z. 2021

    Abstract

    BACKGROUND: The 8th edition staging for non-small cell lung cancer reclassified tumors >7 cm as stage IIIA (T4N0); previously, such tumors without nodal disease were considered stage IIB (T3N0). This study tested the hypothesis that induction chemotherapy for these stage IIIA patients does not improve survival compared to primary surgery.METHODS: The National Cancer Database was queried for non-small cell lung cancer patients with tumor size >7 cm who underwent surgical resection from 2010 - 2015. Patients with clinically node-positive disease or tumor invasion of major structures were excluded. Patients undergoing induction chemotherapy followed by surgery (IC) were compared to patients undergoing primary surgery (PS). Propensity-score matching was performed.RESULTS: In total, 1,610 patients with cT4N0 disease based on tumor size >7 cm and no tumor invasion underwent surgical resection: 1,346 (83.6%) comprised the PS group and 264 (16.4%) the IC group. After propensity-score matching, IC had a higher rate of pN0 (78.4% vs 66.0%, p<0.001) and less lymphovascular invasion (13.9% vs 26.3%, p<0.001), but longer postoperative stay (6 vs 5 days, p<0.001) and higher 30-day mortality (3.5% vs 0%, p=0.002). Median 5-year survival was similar between IC and PS (53.5% vs 62.2%, p=0.075), and IC was not independently associated with survival (HR 1.45, p=0.146).CONCLUSIONS: Patients with cT4N0 non-small cell lung cancer based on tumor size >7 cm and no tumor invasion of major structures have similar overall survival with either IC or PS. IC should not be routinely given for this subset of stage IIIA patients.

    View details for DOI 10.1016/j.athoracsur.2021.07.058

    View details for PubMedID 34425099

  • Surgical resection for patients with pulmonary aspergillosis in the national inpatient sample. Journal of thoracic disease Patel, D. C., Bhandari, P., Epstein, D. J., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2021; 13 (8): 4977-4987

    Abstract

    The role of lung resection in patients with pulmonary aspergillosis is generally reserved for those with localized disease who fail medical management. We used a national database to investigate the influence of preoperative patient comorbidities on inpatient mortality and need for surgery.Patients admitted with pulmonary aspergillosis between 2007 to 2015 were identified in the National Inpatient Sample dataset. Inpatient mortality rates were compared between patients treated medically and surgically. Predictors of mortality, surgical intervention, and non-elective admission were evaluated using multivariable logistic regression.Among a population estimate of 112,998 patients with pulmonary aspergillosis, 107,606 (95.2%) underwent medical management alone and 5,392 (4.8%) underwent surgical resection. Positive predictors for surgery included hemoptysis, and history of lung cancer or chronic pulmonary diseases. Surgically treated patients had a lower inpatient mortality when compared to those treated medically (11.5% vs. 15.1%, P<0.001) in univariate analysis, but this finding did not persist in multivariable analysis (AOR 0.97, P=0.509). The odds of mortality were lower in patients undergoing video assisted thoracoscopic surgery compared to an open approach (AOR 0.77, P=0.001). Among patients treated surgically, mortality was higher in those with a history of lung cancer, solid organ transplantation, liver disease, human immunodeficiency virus infection, hematologic diseases, chronic pulmonary diseases, and those admitted non-electively requiring surgery.In this generalizable study, medical and surgical management of pulmonary aspergillosis were comparable in terms of inpatient mortality. However, non-elective admission and patients with select comorbidities have significantly worse outcomes after surgical intervention.

    View details for DOI 10.21037/jtd-21-151

    View details for PubMedID 34527336

    View details for PubMedCentralID PMC8411153

  • Short-term and intermediate-term readmission after esophagectomy. Journal of thoracic disease Wang, Y., Yang, C. J., He, H., Buchan, J. M., Patel, D. C., Liou, D. Z., Lui, N. S., Berry, M. F., Shrager, J. B., Backhus, L. M. 2021; 13 (8): 4678-4689

    Abstract

    The objective of this study was to characterize short- and intermediate-term readmissions following esophagectomy and to identify predictors of readmission in these two groups.Patients who underwent esophagectomy in the National Readmissions Database (2013-2014) were grouped according to whether first readmission was "short-term" (readmitted <30 days) or "intermediate-term" (readmitted 31-90 days) following index admission for esophagectomy. Predictors of readmission were evaluated using multivariable logistic regression modeling.Of the 3,005 patients who underwent esophagectomy, 544 (18.1%) had a short-term readmission and 305 (10.1%) had an intermediate-term readmission. The most frequent reasons for short-term readmission were post-operative infection (7.5%), dysphagia (6.3%) and pneumonia (5.1%). The most common intermediate-term complications were pneumonia (7.2%), gastrointestinal stricture/stenosis (6.9%) and dysphagia (5.9%). In multivariable analysis, being located in a micropolitan area, increasing number of comorbidities and higher severity of illness score were associated with an increased likelihood of having a short-term readmission while being discharged to a facility (as opposed to directly home) was associated with increased likelihood of both short- and intermediate-term readmission (all P<0.05).In this analysis, postoperative infection was the most common reason for short-term readmission. Dysphagia and pneumonia were common reasons for both short- and intermediate-term readmission of patients following esophagectomy. Interventions focused on reducing the risk of postoperative infection and pneumonia may reduce hospital readmissions. Gastrointestinal stricture and dysphagia were associated with increased risk of intermediate readmission and should be examined in the context of morbidity associated with pyloric procedures (e.g., pyloromyotomy) at the time of esophagectomy.

    View details for DOI 10.21037/jtd-21-637

    View details for PubMedID 34527309

    View details for PubMedCentralID PMC8411130

  • Surgical resection for patients with pulmonary aspergillosis in the national inpatient sample JOURNAL OF THORACIC DISEASE Patel, D. C., Bhandari, P., Epstein, D. J., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B., Lui, N. S. 2021
  • Short-term and intermediate-term readmission after esophagectomy JOURNAL OF THORACIC DISEASE Wang, Y., Yang, C., He, H., Buchan, J. M., Patel, D. C., Liou, D. Z., Lui, N. S., Berry, M. F., Shrager, J. B., Backhus, L. M. 2021
  • Early Discharge after Lobectomy for Lung Cancer does not Equate to Early Readmission. The Annals of thoracic surgery Patel, D. C., Leipzig, M., Jeffrey Yang, C., Wang, Y., Shrager, J. B., Backhus, L. M., Lui, N. S., Liou, D. Z., Berry, M. F. 2021

    Abstract

    BACKGROUND: Enhanced recovery after surgery (ERAS) pathways in several specialties reduce length of stay, but accelerated discharge after thoracic surgery is not well characterized. This study tested the hypothesis that patients discharged on post-operative day 1 (POD1) after lobectomy for lung cancer have an increased risk of readmission.METHODS: Patients who underwent a lobectomy for lung cancer between 2011-2019 in the American College of Surgeons National Surgical Quality Improvement Program database were identified. Readmission rates were compared between patients discharged on postoperative day 1 (POD1) and patients discharged POD 2-6. Early discharge and readmission predictors were evaluated using multivariable logistic regression analysis.RESULTS: Only 854 (3.8%) of 22,585 patients that met inclusion criteria were discharged on POD1, though POD1 discharge rates increased from 2.3% to 8.1% (p< 0.001) from 2011 to 2019. Median hospitalization for POD2-6 patients was 4 days (IQR: 3-5). Patient characteristics associated with a lower likelihood of POD1 discharge were increasing age, smokers, or history of dyspnea, while a minimally invasive approach was the strongest predictor of early discharge (AOR 5.42, p<0.001). Readmission rates were not significantly different for POD1 and POD2-6 groups in univariate analysis (6.0% vs 7.0%, p=0.269). Further, POD1 discharge was not a risk factor for readmission in multivariable analysis (AOR 1.10, p=0.537).CONCLUSIONS: Select patients can be discharged on POD1 after lobectomy for lung cancer without an increased readmission risk, supporting this accelerated discharge target inclusion in lobectomy ERAS protocols.

    View details for DOI 10.1016/j.athoracsur.2021.05.053

    View details for PubMedID 34126077

  • Influence of facility volume on long-term survival of patients undergoing esophagectomy for esophageal cancer. The Journal of thoracic and cardiovascular surgery Patel, D. C., Jeffrey Yang, C., He, H., Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2021

    Abstract

    OBJECTIVE: This study investigated the influence of facility volume on long-term survival in patients with esophageal cancer treated with esophagectomy.METHODS: Patients treated with esophagectomy for cT1 3N0 3M0 adenocarcinoma or squamous cell carcinoma of the mid-distal esophagus in the National Cancer Database between 2006 and 2013 were stratified by annual facility esophagectomy volume dichotomized as more/less than both 6 and 20. Patient characteristics associated with facility volume were evaluated using logistic regression, and the influence of facility volume on survival was evaluated with Kaplan-Meier curves, Cox proportional hazards methods, and propensity matched analysis.RESULTS: Of 11,739 patients who had esophagectomy at 1018 facilities where annual volume ranged from 1 to 47.6 cases, 4262 (36.3%) were treated at 44 facilities with annual esophagectomy volume>6 and 1515 (12.9%) were treated at 7 facilities with annual volume>20. Higher volume was associated with significantly better 5-year survival for both annual volume > 6 (47.6% vs 40.2%; P<.001) and annual volume>20 (47.2% vs 42.3%; P<.001), which persisted in propensity matched analyses as well as Cox multivariable analysis (hazard ratio, 0.81; 95% confidence interval, 0.74-0.89; P<.001 for facility volume>6 and hazard ratio, 0.78; 95% confidence interval, 0.65-0.95; P=.01 for facility volume>20). In Cox multivariable analysis that considered facility volume as a continuous variable, higher volume continued to be associated with better survival (hazard ratio, 0.93 per 5 cases; 95% CI, 0.91-0.96; P<.001).CONCLUSIONS: Esophageal cancer patients treated with esophagectomy at higher volume facilities have significantly better long-term survival than patients treated at lower volume facilities.

    View details for DOI 10.1016/j.jtcvs.2021.05.048

    View details for PubMedID 34247867

  • A new model using artificial intelligence to predict recurrence after surgical resection of stage I-II non-small cell lung cancer. Lui, N., Wei, N., Trope, W., Nesbit, S., Bhandari, P., Lee, C., Hu, H., Guo, H., Liou, D. Z., Shrager, J. B., Backhus, L., Berry, M. F., Yang, E. LIPPINCOTT WILLIAMS & WILKINS. 2021
  • ACR Appropriateness Criteria Intensive Care Unit Patients. Journal of the American College of Radiology : JACR Expert Panel on Thoracic Imaging, Laroia, A. T., Donnelly, E. F., Henry, T. S., Berry, M. F., Boiselle, P. M., Colletti, P. M., Kuzniewski, C. T., Maldonado, F., Olsen, K. M., Raptis, C. A., Shim, K., Wu, C. C., Kanne, J. P. 2021; 18 (5S): S62–S72

    Abstract

    Chest radiography is the most frequent and primary imaging modality in the intensive care unit (ICU), given its portability, rapid image acquisition, and availability of immediate information on the bedside preview. Due to the severity of underlying disease and frequent need of placement of monitoring devices, ICU patients are very likely to develop complications related to underlying disease process and interventions. Portable chest radiography in the ICU is an essential tool to monitor the disease process and the complications from interventions; however, it is subject to overuse especially in stable patients. Restricting the use of chest radiographs in the ICU to only when indicated has not been shown to cause harm. The emerging role of bedside point-of-care lung ultrasound performed by the clinicians is noted in the recent literature. The bedside lung ultrasound appears promising but needs cautious evaluation in the future to determine its role in ICU patients. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

    View details for DOI 10.1016/j.jacr.2021.01.017

    View details for PubMedID 33958119

  • Investigating gene expression profiles associated with clinical radiation resistance in KEAP1/NFE2L2 wildtype lung cancer. Binkley, M. S., Jeon, Y., Nesselbush, M., Moding, E. J., Nabet, B., Almanza, D., Yoo, C., Kurtz, D. M., Owen, S., Backhus, L. M., Berry, M. F., Shrager, J. B., Ramchandran, K. J., Padda, S. K., Das, M., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. AMER ASSOC CANCER RESEARCH. 2021
  • Cancer diagnoses and survival rise as 65-year-olds become Medicare-eligible. Cancer Patel, D. C., He, H., Berry, M. F., Yang, C. J., Trope, W. L., Wang, Y., Lui, N. S., Liou, D. Z., Backhus, L. M., Shrager, J. B. 2021

    Abstract

    BACKGROUND: A Medicare effect has been described to account for increased health care utilization occurring at the age of 65 years. The existence of such an effect in cancer care, where it would be most likely to reduce mortality, has been unclear.METHODS: Patients aged 61 to 69 years who were diagnosed with lung, breast, colon, or prostate cancer from 2004 to 2016 were identified with the Surveillance, Epidemiology, and End Results database and were dichotomized on the basis of eligibility for Medicare (61-64 vs 65-69 years). With age-over-age (AoA) percent change calculations, trends in cancer diagnoses and staging were characterized. After matching, uninsured patients who were 61 to 64 years old (pre-Medicare group) were compared with insured patients who were 65 to 69 years old (post-Medicare group) with respect to cancer-specific mortality.RESULTS: In all, 134,991 patients were identified with lung cancer, 175,558 were identified with breast cancer, 62,721 were identified with colon cancer, and 238,823 were identified with prostate cancer. The AoA growth in the number of cancer diagnoses was highest at the age of 65 years in comparison with all other ages within the decade for all 4 cancers (P < .01, P < .001, P < .01, and P < .001, respectively). In a comparison of diagnoses at the age of 65 years with those in the 61- to 64-year-old cohort, the greatest difference for all 4 cancers was seen in stage I. In matched analyses, the 5-year cancer-specific mortality was worse for lung (86.3% vs 78.5%; P < .001), breast (32.7% vs 11.0%; P < .001), colon (57.1% vs 35.6%; P < .001), and prostate cancer (16.9% vs 4.8%; P < .001) in the uninsured pre-Medicare group than the insured post-Medicare group.CONCLUSIONS: The age threshold of 65 years for Medicare eligibility is associated with more cancer diagnoses (particularly stage I), and this results in lower long-term cancer-specific mortality for all cancers studied.LAY SUMMARY: Contributing to the current debate regarding Medicare for all, this study shows that the expansion of Medicare would improve cancer outcomes for the near elderly.

    View details for DOI 10.1002/cncr.33498

    View details for PubMedID 33778953

  • A National Analysis of Short-term Outcomes and Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Clinical Stage II Non-Small-Cell Lung Cancer ANNALS OF SURGERY Yang, C., Kumar, A., Deng, J. Z., Raman, V., Lui, N. S., D'Amico, T. A., Berry, M. F. 2021; 273 (3): 595–605
  • Endoscopic Instead of Surgical Resection of Tracheal ACC: Maybe, But Not So Fast... reply ANNALS OF THORACIC SURGERY Shah, S. A., Yang, C., Berry, M. F. 2021; 111 (3): 1094
  • Strong for Surgery: Association Between Bundled Risk Factors and Outcomes After Major Elective Surgery in the VA Population. World journal of surgery Liou, D. Z., Patel, D. C., Bhandari, P., Wren, S. M., Marshall, N. J., Harris, A. H., Shrager, J. B., Berry, M. F., Lui, N. S., Backhus, L. M. 2021

    Abstract

    BACKGROUND: Strong for Surgery (S4S) is a public health campaign focused on optimizing patient health prior to surgery by identifying evidence-based modifiable risk factors. The potential impact of S4S bundled risk factors on outcomes after major surgery has not been previously studied. This study tested the hypothesis that a higher number of S4S risk factors is associated with an escalating risk of complications and mortality after major elective surgery in the VA population.METHODS: The Veterans Affairs Surgical Quality Improvement Program (VASQIP) database was queried for patients who underwent major non-emergent general, thoracic, vascular, urologic, and orthopedic surgeries between the years 2008 and 2015. Patients with complete data pertaining to S4S risk factors, specifically preoperative smoking status, HbA1c level, and serum albumin level, were stratified by number of positive risk factors, and perioperative outcomes were compared.RESULTS: A total of 31,285 patients comprised the study group, with 16,630 (53.2%) patients having no S4S risk factors (S4S0), 12,323 (39.4%) having one (S4S1), 2,186 (7.0%) having two (S4S2), and 146 (0.5%) having three (S4S3). In the S4S1 group, 60.3% were actively smoking, 35.2% had HbA1c>7, and 4.4% had serum albumin<3. In the S4S2 group, 87.8% were smokers, 84.8% had HbA1c>7, and 27.4% had albumin<3. Major complications, reoperations, length of stay, and 30-day mortality increased progressively from S4S0 to S4S3 groups. S4S3 had the greatest adjusted mortality risk (adjusted odds radio [AOR] 2.56, p=0.04) followed by S4S2 (AOR 1.58, p=0.02) and S4S1 (AOR 1.34, p=0.02).CONCLUSION: In the VA population, patients who had all three S4S risk factors, namely active smoking, suboptimal nutritional status, and poor glycemic control, had the greatest risk of postoperative mortality compared to patients with fewer S4S risk factors.

    View details for DOI 10.1007/s00268-021-05979-8

    View details for PubMedID 33598723

  • Resection of a Giant Epithelioid Hemangioendothelioma Arising from the Superior Vena Cava. The Annals of thoracic surgery Elliott, I. A., Kasinpila, P., Guenthart, B. A., MacArthur, J. W., Berry, M. F. 2021

    Abstract

    Epithelioid hemangioendothelioma is a rare malignant vascular sarcoma. Here we present a patient with a very large tumor arising from the superior vena cava (SVC), in whom a resection with negative margins was accomplished using veno-venous bypass and bovine pericardial patch reconstruction of the SVC.

    View details for DOI 10.1016/j.athoracsur.2021.01.034

    View details for PubMedID 33529605

  • Use of a Personalized Multimedia Education Platform Improves Preoperative Teaching for Lung Cancer Patients. Seminars in thoracic and cardiovascular surgery Benson, J. n., Bhandari, P. n., Lui, N. n., Berry, M. n., Liou, D. Z., Shrager, J. n., Ayers, K. n., Backhus, L. M. 2021

    Abstract

    We sought to develop and evaluate a personalized multimedia education (ME) tool for pre-operative patient education to improve patient health knowledge, quality of life and satisfaction with care in thoracic surgery. The ME tool was developed and deployed in outpatient clinic during preoperative teaching for patients undergoing surgical resection for lung cancer for quality improvement. Patients were given an electronic survey prior to preoperative teaching and at initial post-operative visit to assess teaching effectiveness and care satisfaction. Sequential patients received either standard preoperative teaching or teaching using the ME tool. Pre- and postoperative survey responses were compared using independent sample paired t-test and multivariable linear regression modeling for adjustment. The final ME tool was an iPad application that incorporated real-time annotations of 3-dimensional, interactive anatomic diagrams. The tool featured video tours of operations, and radiology image import for annotation by the surgeon. Forty-eight patients were included in this pilot study (standard education (SE) n=26; ME, n=22). ME patients had significantly higher satisfaction scores compared to SE patients with respect to length of education materials, clarity of content, supportiveness of content and willingness to recommend materials to others. There was no difference in length of clinic visit between groups. Both patient and provider input can be used to create an innovative electronic preoperative educational tool that prepares and empowers patients in shared decision-making before surgery. Improvements in health literacy and self-efficacy may be more difficult to achieve but remain important as multimedia teaching tools are further developed.

    View details for DOI 10.1053/j.semtcvs.2021.03.003

    View details for PubMedID 33711462

  • Treatment for Early-Stage Lung Cancer Should Never Be "Just a Wedge". The Annals of thoracic surgery Berry, M. F. 2021

    View details for DOI 10.1016/j.athoracsur.2021.09.004

    View details for PubMedID 34582755

  • Perioperative Outcomes After Combined Esophagectomy and Lung Resection. The Journal of surgical research Patel, D. C., Bhandari, P., Shrager, J. B., Berry, M. F., Backhus, L. M., Lui, N. S., Liou, D. Z. 2021; 270: 413-420

    Abstract

    The impact of concomitant lung resection during esophagectomy on short-term outcomes is not well characterized. This study tests the hypothesis that lung resection at the time of esophagectomy is not associated with increased perioperative morbidity or mortality.Perioperative outcomes for esophageal cancer patients who underwent esophagectomy alone (EA) were compared to patients who had concurrent esophagectomy and lung resection (EL) using the NSQIP database between 2006-2017. Predictors of morbidity and mortality, including combined surgery, were evaluated using multivariable logistic regression.Among the 6,225 study patients, 6,068 (97.5%) underwent EA and 157 (2.5%) underwent EL. There were no differences in baseline characteristics between the two groups. Operating time for EL was longer than EA (median 416 versus 371 minutes, P < 0.01). Median length of stay was 10 d for both groups. Perioperative mortality was not significantly different between EL and EA patients (5.1% versus 2.8%, P = 0.08). EL patients had higher rates of postoperative pneumonia (22.3% versus 16.2%, P = 0.04) and sepsis (11.5% versus 7.1%, P = 0.03), however major complication rates overall were similar (40.8% versus 35.3%, P = 0.16). Combining lung resection with esophagectomy was not independently associated with increased postoperative morbidity (AOR 1.21 [95% CI 0.87-1.69]) or mortality (AOR 1.63 [95% CI 0.74-3.58]).Concurrent lung resection during esophagectomy is not associated with increased mortality or overall morbidity, but is associated with higher rates of pneumonia beyond esophagectomy alone. Surgeons considering combined lung resection with esophagectomy should carefully evaluate the patient's risk for pulmonary complications and pursue interventions preoperatively to optimize respiratory function.

    View details for DOI 10.1016/j.jss.2021.09.037

    View details for PubMedID 34775148

  • Global analysis of shared T cell specificities in human non-small cell lung cancer enables HLA inference and antigen discovery. Immunity Chiou, S. H., Tseng, D. n., Reuben, A. n., Mallajosyula, V. n., Molina, I. S., Conley, S. n., Wilhelmy, J. n., McSween, A. M., Yang, X. n., Nishimiya, D. n., Sinha, R. n., Nabet, B. Y., Wang, C. n., Shrager, J. B., Berry, M. F., Backhus, L. n., Lui, N. S., Wakelee, H. A., Neal, J. W., Padda, S. K., Berry, G. J., Delaidelli, A. n., Sorensen, P. H., Sotillo, E. n., Tran, P. n., Benson, J. A., Richards, R. n., Labanieh, L. n., Klysz, D. D., Louis, D. M., Feldman, S. A., Diehn, M. n., Weissman, I. L., Zhang, J. n., Wistuba, I. I., Futreal, P. A., Heymach, J. V., Garcia, K. C., Mackall, C. L., Davis, M. M. 2021; 54 (3): 586–602.e8

    Abstract

    To identify disease-relevant T cell receptors (TCRs) with shared antigen specificity, we analyzed 778,938 TCRβ chain sequences from 178 non-small cell lung cancer patients using the GLIPH2 (grouping of lymphocyte interactions with paratope hotspots 2) algorithm. We identified over 66,000 shared specificity groups, of which 435 were clonally expanded and enriched in tumors compared to adjacent lung. The antigenic epitopes of one such tumor-enriched specificity group were identified using a yeast peptide-HLA A∗02:01 display library. These included a peptide from the epithelial protein TMEM161A, which is overexpressed in tumors and cross-reactive epitopes from Epstein-Barr virus and E. coli. Our findings suggest that this cross-reactivity may underlie the presence of virus-specific T cells in tumor infiltrates and that pathogen cross-reactivity may be a feature of multiple cancers. The approach and analytical pipelines generated in this work, as well as the specificity groups defined here, present a resource for understanding the T cell response in cancer.

    View details for DOI 10.1016/j.immuni.2021.02.014

    View details for PubMedID 33691136

  • Endoscopic instead of surgical resection of tracheal ACC - maybe, but not so fast. The Annals of thoracic surgery Shah, S., Jeffrey Yang, C., Berry, M. F. 2020

    View details for DOI 10.1016/j.athoracsur.2020.08.078

    View details for PubMedID 33189671

  • ACR Appropriateness Criteria Blunt Chest Trauma-Suspected Cardiac Injury. Journal of the American College of Radiology : JACR Expert Panels on Cardiac Imaging and Thoracic Imaging, Stojanovska, J., Hurwitz Koweek, L. M., Chung, J. H., Ghoshhajra, B. B., Walker, C. M., Beache, G. M., Berry, M. F., Colletti, P. M., Davis, A. M., Hsu, J. Y., Khosa, F., Kicska, G. A., Kligerman, S. J., Litmanovich, D., Maroules, C. D., Meyersohn, N., Syed, M. A., Tong, B. C., Villines, T. C., Wann, S., Wolf, S. J., Kanne, J. P., Abbara, S. 2020; 17 (11S): S380–S390

    Abstract

    Blunt cardiac injuries range from myocardial concussion (commotio cordis) leading to fatal ventricular arrhythmias to myocardial contusion, cardiac chamber rupture, septal rupture, pericardial rupture, and valvular injuries. Blunt injuries account for one-fourth of the traumatic deaths in the United States. Chest radiography, transthoracic echocardiography, CT chest with and without contrast, and CT angiography are usually appropriate as the initial examination in patients with suspected blunt cardiac injury who are both hemodynamically stable and unstable. Transesophageal echocardiography and CT heart may be appropriate as examination in patients with suspected blunt cardiac injuries. This publication of blunt chest trauma-suspected cardiac injuries summarizes the literature and makes recommendations for imaging based on the available data and expert opinion. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

    View details for DOI 10.1016/j.jacr.2020.09.012

    View details for PubMedID 33153551

  • Greater Ipsilateral Rectus Muscle Atrophy after Robotic Thoracic Surgery Compared to Open and VATS Approaches Wang, Y., Bhandari, P., Trope, W., Guenthart, B. A., Guo, H., Liou, D., Backhus, L. M., Berry, M., Ben Shrager, J., Lui, N. ELSEVIER SCIENCE INC. 2020: S289
  • KEAP1/NFE2L2 mutations to predict local recurrence after radiotherapy but not surgery in localized non-small cell lung cancer. Binkley, M. S., Jeon, Y., Nesselbush, M., Moding, E. J., Nabet, B., Almanza, D. S., Yoo, C., Kurtz, D., Owen, S., Backhus, L., Berry, M. F., Shrager, J. B., Ramchandran, K., Padda, S., Das, M., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. AMER SOC CLINICAL ONCOLOGY. 2020
  • Cancer diagnoses and survival rise as 65-year-olds become Medicare eligible. Patel, D. C., He, H., Berry, M. F., Yang, C., Trope, W., Lui, N., Liou, D. Z., Backhus, L., Shrager, J. B. AMER SOC CLINICAL ONCOLOGY. 2020
  • Discovery of a novel shared tumor antigen in human lung cancer. Tseng, D., Chiou, S., Yang, X., Reuben, A., Wilhelmy, J., McSween, A., Conley, S., Sinha, R., Nabet, B., Wang, C., Shrager, J. B., Berry, M. F., Backhus, L., Lui, n., Wakelee, H. A., Neal, J. W., Zhang, J., Garcia, K., Mackall, C., Davis, M. AMER SOC CLINICAL ONCOLOGY. 2020
  • Reply: The importance of appropriate selection for segmentectomy. The Journal of thoracic and cardiovascular surgery Jeffrey Yang, C., Berry, M. F. 2020

    View details for DOI 10.1016/j.jtcvs.2020.03.146

    View details for PubMedID 32386765

  • Sub-solid lung adenocarcinoma in Asian versus Caucasian patients: different biology but similar outcomes. Journal of thoracic disease Lui, N. S., Benson, J., He, H., Imielski, B. R., Kunder, C. A., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B. 2020; 12 (5): 2161-2171

    Abstract

    Asian and Caucasian patients with lung cancer have been compared in several database studies, with conflicting findings regarding survival. However, these studies did not include proportion of ground-glass opacity or mutational status in their analyses. Asian patients commonly develop sub-solid lung adenocarcinomas that harbor EGFR mutations, which have a better prognosis. We hypothesized that among patients undergoing surgery for sub-solid lung adenocarcinomas, Asian patients have better survival compared to Caucasian patients.We identified Asian and Caucasian patients who underwent surgical resection for a sub-solid lung adenocarcinoma from 2002 to 2015 at our institution. Sub-solid was defined as ≥10% ground-glass opacity on preoperative CT scan or ≥10% lepidic component on surgical pathology. Time-to-event multivariable analysis was performed to determine which characteristics were associated with recurrence and survival.Two hundred twenty-four patients were included with median follow up 48 months. Asian patients were more likely to be never smokers (76.3% vs. 29.0%, P<0.01) and have an EGFR mutation (69.4% vs. 25.6% of those tested, P<0.01), while Caucasian patients were more likely to have a KRAS mutation (23.5% vs. 4.9% of those tested, P<0.01). There was a trend towards Asian patients having a higher proportion of ground-glass opacity (38.8% vs. 30.5%, P=0.11). Time-to-event multivariable analysis showed that higher proportion of ground-glass opacity was significantly associated with better recurrence-free survival (HR 0.76 per 20% increase, P=0.02). However, mutational status and race did not have a significant impact on recurrence-free or overall survival.Asian and Caucasian patients with sub-solid lung adenocarcinoma have different tumor biology, but recurrence-free and overall survival after surgical resection is similar.

    View details for DOI 10.21037/jtd.2020.04.37

    View details for PubMedID 32642121

    View details for PubMedCentralID PMC7330405

  • Sub-solid lung adenocarcinoma in Asian versus Caucasian patients: different biology but similar outcomes JOURNAL OF THORACIC DISEASE Lui, N. S., Benson, J., He, H., Imielski, B. R., Kunder, C. A., Liou, D. Z., Backhus, L. M., Berry, M. F., Shrager, J. B. 2020; 12 (5): 2161–71
  • Impact of Surveillance After Lobectomy for Lung Cancer on Disease Detection and Survival. Clinical lung cancer Mayne, N. R., Mallipeddi, M. K., Darling, A. J., Jeffrey Yang, C., Eltaraboulsi, W. R., Shoffner, A. R., Naqvi, I. A., D'Amico, T. A., Berry, M. F. 2020

    Abstract

    INTRODUCTION: Existing guidelines for surveillance after non-small-cell lung cancer (NSCLC) treatment are inconsistent and have relatively sparse supporting literature. This study characterizes detection rates of metachronous and recurrent disease during surveillance with computed tomography scans after definitive treatment of early stage NSCLC.MATERIALS AND METHODS: The incidence of metachronous and recurrent disease in patients who previously underwent complete resection via lobectomy for stage IA NSCLC at a single center from 1996 to 2010 were evaluated. A subgroup analysis was used to compare survival of patients whose initial surveillance scan was 6 ± 3 months (early) versus 12 ± 3 months (late) after lobectomy.RESULTS: Of 294 eligible patients, 49 (17%) developed recurrent disease (14 local only, 35 distant), and 45 (15%) developed new NSCLC. Recurrent disease was found at a mean of 22 ± 19 months, and new primaries were found at a mean of 52 ± 31 months after lobectomy (P< .01). Five-year survival after diagnosis of recurrent disease was significantly lower than after diagnosis of second primaries (2.3% vs. 57.5%; P< .001). In the subgroup analysis of 187 patients, both disease detection on the initial scan (2% [2/94] vs. 4% [4/93]; P= .44) and 5-year survival (early, 80.8% vs. late, 86.7%; P= .61) were not significantly different between the early (n= 94) and the late (n= 93) groups.CONCLUSION: Surveillance after lobectomy for stage IA NSCLC is useful for identifying both new primary as well as recurrent disease, but waiting to start surveillance until 12 ± 3 months after surgery is unlikely to miss clinically important findings.

    View details for DOI 10.1016/j.cllc.2020.03.011

    View details for PubMedID 32376115

  • Integrating genomic features for non-invasive early lung cancer detection. Nature Chabon, J. J., Hamilton, E. G., Kurtz, D. M., Esfahani, M. S., Moding, E. J., Stehr, H., Schroers-Martin, J., Nabet, B. Y., Chen, B., Chaudhuri, A. A., Liu, C. L., Hui, A. B., Jin, M. C., Azad, T. D., Almanza, D., Jeon, Y. J., Nesselbush, M. C., Co Ting Keh, L., Bonilla, R. F., Yoo, C. H., Ko, R. B., Chen, E. L., Merriott, D. J., Massion, P. P., Mansfield, A. S., Jen, J., Ren, H. Z., Lin, S. H., Costantino, C. L., Burr, R., Tibshirani, R., Gambhir, S. S., Berry, G. J., Jensen, K. C., West, R. B., Neal, J. W., Wakelee, H. A., Loo, B. W., Kunder, C. A., Leung, A. N., Lui, N. S., Berry, M. F., Shrager, J. B., Nair, V. S., Haber, D. A., Sequist, L. V., Alizadeh, A. A., Diehn, M. 2020; 580 (7802): 245-251

    Abstract

    Radiologic screening of high-risk adults reduces lung-cancer-related mortality1,2; however, a small minority of eligible individuals undergo such screening in the United States3,4. The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)5, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.

    View details for DOI 10.1038/s41586-020-2140-0

    View details for PubMedID 32269342

  • Integrating genomic features for non-invasive early lung cancer detection NATURE Chabon, J. J., Hamilton, E. G., Kurtz, D. M., Esfahani, M. S., Moding, E. J., Stehr, H., Schroers-Martin, J., Nabet, B. Y., Chen, B., Chaudhuri, A. A., Liu, C., Hui, A. B., Jin, M. C., Azad, T. D., Almanza, D., Jeon, Y., Nesselbush, M. C., Keh, L., Bonilla, R. F., Yoo, C. H., Ko, R. B., Chen, E. L., Merriott, D. J., Massion, P. P., Mansfield, A. S., Jen, J., Ren, H. Z., Lin, S. H., Costantino, C. L., Burr, R., Tibshirani, R., Gambhir, S. S., Berry, G. J., Jensen, K. C., West, R. B., Neal, J. W., Wakelee, H. A., Loo, B. W., Kunder, C. A., Leung, A. N., Lui, N. S., Berry, M. F., Shrager, J. B., Nair, V. S., Haber, D. A., Sequist, L. V., Alizadeh, A. A., Diehn, M. 2020
  • A National Analysis of Treatment Patterns and Outcomes for Patients 80 Years or Older with Esophageal Cancer. Seminars in thoracic and cardiovascular surgery Yang, C. J., Wang, Y. n., Raman, V. n., Patel, D. n., Lui, N. n., Backhus, L. n., Shrager, J. n., Berry, M. F., Liou, D. n. 2020

    Abstract

    The purpose of this study was to evaluate practice patterns and outcomes for patients 80 years or older with esophageal cancer using a nationwide cancer database. Practice patterns for patients 80 years or older with stage I-IV esophageal cancer in the National Cancer Database from 2004-2014 were analyzed. Overall survival associated with different treatment strategies were evaluated using the Kaplan-Meier method and multivariable Cox proportional hazard models. In the study period, 40.5% and 46.2% of patients with stage I adenocarcinoma and squamous cell carcinoma, respectively, did not receive any treatment at all. Less than 11% (196/1,865) of patients with stage I-II disease underwent esophagectomy, even though surgery was associated with a better 5-year survival compared to no treatment (stage I: 47.3% [95% CI 36.2%-57.6%] vs 14.9% [95% CI: 11.2%-19.1%]; stage II: 29.3% [95% CI 20.1%-39.1%] vs 1.2% [95% CI: 0.1%-5.5%]). Of the 1,596 (37.7%) patients with stage III disease who received curative-intent treatment (surgery or chemoradiation), the 5-year survival was significantly better than that of patients who received no treatment (11.9% [95% CI: 9.7%-14.4% vs 4.3% [95% CI: 1.9%-8.3%]). In this national analysis of patients 80 years and older with esophageal cancer, over 40% of patients with stage I disease did not receive treatment. Patients with stage I-III disease had better survival and risks and benefits of treatment for elderly patients should be discussed in a multidisciplinary setting.

    View details for DOI 10.1053/j.semtcvs.2020.09.004

    View details for PubMedID 32977014

  • Perioperative Outcomes and 5-year Survival After Open versus Thoracoscopic Sleeve Resection for Lung Cancer. Seminars in thoracic and cardiovascular surgery Mayne, N. R., Darling, A. J., Raman, V. n., Balderson, S. n., Berry, M. F., Harpole, D. H., D'Amico, T. A., Yang, C. J. 2020

    Abstract

    The objective of this study was to evaluate the impact of a video-assisted thoracoscopic (VATS) approach on outcomes in patients who underwent sleeve lobectomy for non-small-cell lung cancer (NSCLC). Outcomes of patients with cT1-T3, N0-N2, M0 NSCLC who underwent sleeve lobectomy in the National Cancer Data Base (NCDB) from 2010-2015 were assessed using Kaplan-Meier, propensity score-matching, and Cox proportional hazards analyses. An "intent-to-treat" analysis was performed. In the NCDB, 210 sleeve lobectomy patients met inclusion criteria (VATS 44 [21%], thoracotomy 166 [79%]). Nine (20%) of the VATS cases were converted to open. Compared to an open approach, VATS was associated with no significant differences in lymph nodes examined (median 9.5 vs 9.0, p = 0.72), length of stay (median 6 days vs 6 days, p = 0.36), 30-day mortality (4.5% vs 1.8%; p = 0.28), and 90-day mortality (6.8% vs 4.8%; p = 0.70). There were no significant differences in 5-year survival between the VATS and open groups in both the entire cohort (VATS [85%] vs open [79%]; log-rank p = 0.91) and in a propensity score-matched analysis of 86 patients (log-rank p = 0.75). Furthermore, a VATS approach was also not associated with worse survival in multivariable analysis (HR = 0.64; 95% CI [0.23-1.78]; p = 0.39). In this national analysis, a VATS approach for sleeve lobectomy for NSCLC was not associated with worse short-term or long-term outcomes when compared to an open approach.

    View details for DOI 10.1053/j.semtcvs.2020.08.013

    View details for PubMedID 32858216

  • ACR Appropriateness Criteria® Hemoptysis. Journal of the American College of Radiology : JACR Olsen, K. M., Manouchehr-Pour, S. n., Donnelly, E. F., Henry, T. S., Berry, M. F., Boiselle, P. M., Colletti, P. M., Harrison, N. E., Kuzniewski, C. T., Laroia, A. T., Maldonado, F. n., Pinchot, J. W., Raptis, C. A., Shim, K. n., Tong, B. C., Wu, C. C., Kanne, J. P. 2020; 17 (5S): S148–S159

    Abstract

    Hemoptysis, the expectoration of blood, ranges in severity from nonmassive to massive. This publication reviews the literature on the imaging and treatment of hemoptysis. Based on the literature, the imaging recommendations for massive hemoptysis are both a chest radiograph and CT with contrast or CTA with contrast. Bronchial artery embolization is also recommended in the majority of cases. In nonmassive hemoptysis, both a chest radiograph and CT with contrast or CTA with contrast is recommended. Bronchial artery embolization is becoming more commonly utilized, typically in the setting of failed medical therapy. Recurrent hemoptysis, defined as hemoptysis that recurs following initially successful cessation of hemoptysis, is best reassessed with a chest radiograph and either CT with contrast or CTA with contrast. Bronchial artery embolization is increasingly becoming the treatment of choice in recurrent hemoptysis, with the exception of infectious causes such as in cystic fibrosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

    View details for DOI 10.1016/j.jacr.2020.01.043

    View details for PubMedID 32370959

  • A National Analysis of Minimally Invasive vs Open Segmentectomy for Stage IA Non-small-cell Lung Cancer. Seminars in thoracic and cardiovascular surgery Kumar, A. n., Deng, J. n., Raman, V. n., Okusanya, O. n., Baiu, I. n., Berry, M. F., D'Amico, T. A., Yang, C. J. 2020

    Abstract

    The objective of this study was to compare long-term outcomes of open versus minimally invasive (MIS) segmentectomy for early stage non-small-cell lung cancer (NSCLC), which has not been evaluated using national studies. Outcomes of open versus MIS segmentectomy for clinical T1, N0, M0 NSCLC in the National Cancer Data Base (2010-2015) were evaluated using propensity score matching. Of the 39,351 patients who underwent surgery for stage IA NSCLC from 2010-2015, 770 underwent segmentectomy by thoracotomy and 1,056 by MIS approach (876 thoracoscopic [VATS], 180 robotic). The MIS to open conversion rate was 6.7% (n=71).  After propensity-score matching, all baseline characteristics were well-balanced between the open (n=683) and MIS (n=683) groups. When compared to the open group, the MIS group had shorter median length of stay (LOS) (4 vs 5 days, p<0.001) and lower 30-day mortality (0.6% vs 1.9%, p=0.037). There were no significant differences between MIS and open groups with regard to 30-day readmission (5.0% vs 3.7%, p=0.43), or upstaging from cN0 to pN1/N2/N3 (3.1% vs 3.6%, p=0.89). The MIS approach was associated with similar long-term overall survival as the open approach (5-year survival: 62.3% vs 63.5%, p=0.89; multivariable-adjusted HR: 0.99, 95% CI: 0.82-1.21, p=0.96). In this national analysis of open versus MIS segmentectomy for clinical stage IA NSCLC, MIS was associated with shorter LOS and lower perioperative mortality, and similar nodal upstaging and 5-year survival when compared to segmentectomy via thoracotomy. MIS segmentectomy does not appear to compromise oncologic outcomes for clinical stage IA NSCLC.

    View details for DOI 10.1053/j.semtcvs.2020.09.009

    View details for PubMedID 32977013

  • Transcervical Thymectomy is the Most Cost-Effective Surgical Approach in Myasthenia Gravis. The Annals of thoracic surgery Sholtis, C. n., Teymourtash, M. n., Berry, M. n., Backhus, L. n., Bhandari, P. n., He, H. n., Benson, J. n., Wang, Y. Y., Yevudza, E. n., Lui, N. n., Shrager, J. n. 2020

    Abstract

    Extended thymectomy is now proven to improve the course of myasthenia gravis. Retrospective studies demonstrate that several techniques for thymectomy achieve overlapping remission rates. We therefore compared perioperative outcomes and costs among 3 approaches to thymectomy: sternotomy; video/robot assisted; transcervical.To ensure similar study groups, we excluded patients with >4cm or invasive tumors and those who underwent less than an extended thymectomy or concurrent procedures. Hospital costs were collected and analyzed by blinded finance personnel.The final study group consisted of 25 transcervical, 23 video/robotic, and 14 sternotomy subjects. There was a higher incidence of myasthenia gravis in the transcervical and sternotomy groups (p<0.01) and of thymoma in the video/robotic and sternotomy groups (p<0.01). Mean modified Charlson co-morbidity score was higher for sternotomy (2.7±2.1) than transcervical (1.00±.58; p<0.001) and video/robotic (1.13±.97; p=0.001). There was no difference in complication rates between approaches (p=0.83). The cost of transcervical thymectomy was 45% of the cost of sternotomy (p<0.001) and 58% of the cost of video/robotic (p=0.018) approaches; these differences remained highly significant on multivariate analysis. Transcervical thymectomy had shorter mean length of stay (1.2±.5 days) than median sternotomy (4.4±3.5; p<0.001) and video/robot assisted thymectomy (2.6±.96; p=0.045), and "bed cost" was the major contributor to cost difference between the groups.Transcervical thymectomy, which provides overlapping myasthenia gravis remission rates vs. more invasive approaches, is equally safe and far less costly than sternotomy and video/robotic approaches.

    View details for DOI 10.1016/j.athoracsur.2020.01.047

    View details for PubMedID 32135150

  • Does size matter? A national analysis of the utility of induction therapy for large thymomas. Journal of thoracic disease Liou, D. Z., Ramakrishnan, D. n., Lui, N. S., Shrager, J. B., Backhus, L. M., Berry, M. F. 2020; 12 (4): 1329–41

    Abstract

    Tumor size of 8 cm or greater is a risk factor for recurrence after thymoma resection, but the role of induction therapy for large thymomas is not well defined. This study tested the hypothesis that induction therapy for thymomas 8 cm and larger improves survival.The use of induction therapy for patients treated with surgical resection for Masaoka stage I-III thymomas in the National Cancer Database between 2006-2013 was evaluated using logistic regression, Kaplan-Meier analysis, and Cox-proportional hazards methods.Of the 1,849 patients who met inclusion criteria, 582 (31.5%) had tumors ≥8 cm. Five-year survival was worse in patients with tumors ≥8 cm compared to smaller tumors [84.6% (95% CI: 81.2-88.1%) vs. 89.4% (95% CI: 87.2-91.7%), P=0.003]. Induction therapy was used in 166 (9.0%) patients overall and was more likely in patients with tumors ≥8 cm [adjusted odds ratio (AOR) 3.257, P<0.001]. Induction therapy was not associated with improved survival in the subset of patients with tumors ≥8 cm in either univariate [80.9% (95% CI: 72.6-90.1%) vs. 85.4% (95% CI: 81.8-89.3%), P=0.27] or multivariable analysis [hazard ratio (HR) 1.54, P=0.10]. Increasing age (HR 1.56/decade, P<0.001) and Masaoka stage III (HR 1.76, P=0.04) were associated with worse survival in patients with tumors ≥8 cm.Survival after thymoma resection is worse for tumors 8 cm or larger compared to smaller tumors and is not improved by induction therapy. Size alone should not be a criterion for using induction therapy prior to thymoma resection.

    View details for DOI 10.21037/jtd.2020.02.63

    View details for PubMedID 32395270

    View details for PubMedCentralID PMC7212162

  • A Patient-Specific Mixed-Reality Visualization Tool for Thoracic Surgical Planning. The Annals of thoracic surgery Perkins, S. L., Krajancich, B. n., Jeffrey Yang, C. F., Hargreaves, B. A., Daniel, B. L., Berry, M. F. 2020

    Abstract

    Identifying small lung lesions during minimally invasive thoracic surgery can be challenging. We describe 3D mixed-reality visualization technology that may facilitate non-invasive nodule localization.A software application and medical image processing pipeline were developed for the Microsoft HoloLens to incorporate patient-specific data and provide a mixed-reality tool to explore and manipulate chest anatomy with a custom-designed user interface featuring gesture and voice recognition.A needs assessment between engineering and clinical disciplines identified the potential utility of mixed-reality technology in facilitating safe and effective resection of small lung nodules. Through an iterative process, we developed a prototype employing a wearable headset that allows the user to: (1) view a patient's original preoperative imaging, (2) manipulate a 3D rendering of that patient's chest anatomy including the bronchial, osseus, and vascular structures, and (3) simulate lung deflation and surgical instrument placement.Mixed-reality visualization during surgical planning may facilitate accurate and rapid identification of small lung lesions during minimally invasive surgeries and reduce the need for additional invasive pre-operative localization procedures.

    View details for DOI 10.1016/j.athoracsur.2020.01.060

    View details for PubMedID 32145195

  • KEAP1/NFE2L2 mutations predict lung cancer radiation resistance that can be targeted by glutaminase inhibition. Cancer discovery Binkley, M. S., Jeon, Y. J., Nesselbush, M. n., Moding, E. J., Nabet, B. Y., Almanza, D. n., Kunder, C. n., Stehr, H. n., Yoo, C. H., Rhee, S. n., Xiang, M. n., Chabon, J. J., Hamilton, E. n., Kurtz, D. M., Gojenola, L. n., Owen, S. G., Ko, R. B., Shin, J. H., Maxim, P. G., Lui, N. S., Backhus, L. M., Berry, M. F., Shrager, J. B., Ramchandran, K. J., Padda, S. K., Das, M. n., Neal, J. W., Wakelee, H. A., Alizadeh, A. A., Loo, B. W., Diehn, M. n. 2020

    Abstract

    Tumor genotyping is not routinely performed in localized non-small cell lung cancer (NSCLC) due to lack of associations of mutations with outcome. Here, we analyze 232 consecutive patients with localized NSCLC and demonstrate that KEAP1 and NFE2L2 mutations are predictive of high rates of local recurrence (LR) after radiotherapy but not surgery. Half of LRs occurred in KEAP1/NFE2L2 mutation tumors, indicating they are major molecular drivers of clinical radioresistance. Next, we functionally evaluate KEAP1/NFE2L2 mutations in our radiotherapy cohort and demonstrate that only pathogenic mutations are associated with radioresistance. Furthermore, expression of NFE2L2 target genes does not predict LR, underscoring the utility of tumor genotyping. Finally, we show that glutaminase inhibition preferentially radiosensitizes KEAP1 mutant cells via depletion of glutathione and increased radiation-induced DNA damage. Our findings suggest that genotyping for KEAP1/NFE2L2 mutations could facilitate treatment personalization and provide a potential strategy for overcoming radioresistance conferred by these mutations.

    View details for DOI 10.1158/2159-8290.CD-20-0282

    View details for PubMedID 33071215

  • ACR Appropriateness Criteria® Occupational Lung Diseases. Journal of the American College of Radiology : JACR Cox, C. W., Chung, J. H., Ackman, J. B., Berry, M. F., Carter, B. W., de Groot, P. M., Hobbs, S. B., Johnson, G. B., Maldonado, F. n., McComb, B. L., Tong, B. C., Walker, C. M., Kanne, J. P. 2020; 17 (5S): S188–S197

    Abstract

    Ordering the appropriate diagnostic imaging for occupational lung disease requires a firm understanding of the relationship between occupational exposure and expected lower respiratory track manifestation. Where particular inorganic dust exposures typically lead to nodular and interstitial lung disease, other occupational exposures may lead to isolated small airway obstruction. Certain workplace exposures, like asbestos, increase the risk of malignancy, but also produce pulmonary findings that mimic malignancy. This publication aims to delineate the common and special considerations associated with occupational lung disease to assist the ordering physician in selecting the most appropriate imaging study, while still stressing the importance of a multidisciplinary approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

    View details for DOI 10.1016/j.jacr.2020.01.022

    View details for PubMedID 32370962

  • Paradoxical Motion on Sniff Test Predicts Greater Improvement Following Diaphragm Plication. The Annals of thoracic surgery Patel, D. C., Berry, M. F., Bhandari, P. n., Backhus, L. M., Raees, S. n., Trope, W. n., Nash, A. n., Lui, N. S., Liou, D. Z., Shrager, J. B. 2020

    Abstract

    Diaphragm plication (DP) improves pulmonary function and quality of life for those with diaphragm paralysis/dysfunction. It is unknown whether differing degrees of diaphragm dysfunction as measured by sniff testing impact results after plication.Patients who underwent minimally invasive DP from 2008-2019 were dichotomized based on sniff test results: paradoxical motion (PM) vs. no paradoxical motion (NPM) - the latter including normal/decreased/no motion. Preoperative and postoperative pulmonary function testing (PFT) after DP was compared between the two groups. The impact of diaphragm height index (DHI), a measure of diaphragm elevation, was also assessed.Twenty-six patients underwent preoperative sniff testing, DP, and postoperative PFTs. Including all patients, DP resulted in a 17.8 ± 5.5% (p<0.001) improvement in forced expiratory volume at 1 second (FEV1), a 14.4 ± 5.3% (p<0.001) improvement in forced vital capacity (FVC), and a 4.7 ± 4.6% (p=0.539) improvement in diffusing capacity (DLCO). There were greater improvements in the PM group (n=16) vs. NPM group (n=10) for FEV1 (27.2 ± 6.0% vs. 3.9 ± 6.2%, p=0.017) and FVC (28.1 ± 5.3% vs. -0.5 ± 3.3%, p=0.001). There was no difference in ΔDLCO between groups. There were no differences between patients with PM and NPM in postoperative course/complications. No value for DHI predicted improvement in PFTs following DP.Patients with PM on sniff test have dramatically greater objective improvements in pulmonary function following plication than those without PM. Most patients without PM do not demonstrate improvement in standard PFTs. Improvements in dyspnea require additional study.

    View details for DOI 10.1016/j.athoracsur.2020.07.049

    View details for PubMedID 33031777

  • Commentary: Resection of clinical early-stage lung cancer with unexpected nodal disease-can less really be the same? The Journal of thoracic and cardiovascular surgery Yang, C. J., Berry, M. F. 2019

    View details for DOI 10.1016/j.jtcvs.2019.12.030

    View details for PubMedID 32067788

  • The Oldest Old: A National Analysis of Outcomes for Patients 90 Years or Older With Lung Cancer. The Annals of thoracic surgery Yang, C. J., Brown, A. B., Deng, J. Z., Lui, N. S., Backhus, L. M., Shrager, J. B., D'Amico, T. A., Berry, M. F. 2019

    Abstract

    BACKGROUND: Most clinicians will encounter patients 90 years or older with non-small cell lung cancer (NSCLC), but evidence that informs treatment decisions for this extremely elderly population is lacking. This study evaluated outcomes associated with treatment strategies for this nonagenarian population.METHODS: Treatment and overall survival for patients 90 years and older with NSCLC in the National Cancer Data Base (2004-2014) were evaluated using logistic regression, the Kaplan-Meier method, and multivariable Cox proportional hazard models.RESULTS: The majority (n = 4152, 57.6%) of the 7205 patients 90 years or older with stage I-IV NSCLC did not receive any therapy. For the entire cohort, receiving treatment was associated with significantly better survival when compared with no therapy (5-year survival, 9.3% [95% confidence interval [CI], 8.0%-10.7%] vs 1.7% [95% CI, 1.2%-2.2%]; multivariable adjusted hazard ratio, 0.53; P < .001). Stage I patients had the most pronounced survival benefit with treatment (median survival, 27.4 months vs 10.0 months with no treatment; P < .001). Among this subset of patients with stage I disease (n= 1430), only 12.7% (n= 182) had surgery and 33% (n= 471) had no therapy. In these stage I patients surgery was associated with significantly better 5-year survival (33.7% [95% CI, 25.4%-42.1%]) than nonoperative therapy (17.1% [95% CI, 13.7%-20.8%]) and no therapy (6.2% [95% CI, 3.8%-9.4%]).CONCLUSIONS: Therapy for nonagenarians with NSCLC is associated with a significant survival benefit but is not used in most patients. Treatment should not be withheld for these "oldest old" patients based on their age alone but should be considered based on stage and patient preferences in a multidisciplinary setting.

    View details for DOI 10.1016/j.athoracsur.2019.09.027

    View details for PubMedID 31757356

  • National Evaluation of Short-Term and Intermediate-Term Readmission after Esophagectomy Yang, C. J., Wang, Y., He, H., Liou, D., Lui, N., Berry, M. F., Shrager, J., Backhus, L. ELSEVIER SCIENCE INC. 2019: S279–S280
  • A Multi-Center Analysis of Right vs Left-Sided Pneumonectomy Following Induction Therapy Yang, C. J., Mayne, N., Battoo, A., Yendamuri, S., Demmy, T., Mckenna, R., D'Amico, T., Berry, M. ELSEVIER SCIENCE INC. 2019: S278
  • Broad Genomic Profiling of Bronchoalveolar Lavage Fluid in Lung Cancer Nair, V., Hui, A., Chabon, J., Esfahani, M., Stehr, H., Nabet, B., Benson, J., Chaudhuri, A., Zhou, L., Ayers, K., Bedi, H., Ramsey, M., Van Wert, R., Sung, A., Lui, N., Backhus, L., Berry, M., Massion, P., Shrager, J., Alizadeh, A., Diehn, M. ELSEVIER SCIENCE INC. 2019: S747–S748
  • Management of Benign Esophageal Perforation in the National Inpatient Sample Lui, N., Bhandari, P., Backhus, L., Liou, D., Shrager, J., Berry, M. F. ELSEVIER SCIENCE INC. 2019: E209
  • Response to Comment on "A National Analysis of Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Stage I Nonsmall-cell Lung Cancer'' ANNALS OF SURGERY Yang, C., Kumar, A., Berry, M. F., D'Amico, T. A. 2019; 270 (2): E47
  • The role of thoracoscopic pneumonectomy in the management of non-small cell lung cancer: A multicenter study Yang, C., Yendamuri, S., Mayne, N. R., Battoo, A., Wang, H., Meyerhoff, R., Vandusen, K., Hirji, S. A., Berry, M. E., McKenna, R. J., Demmy, T. L., D'Amico, T. A. MOSBY-ELSEVIER. 2019: 252–62
  • ACR Appropriateness Criteria Noninvasive Clinical Staging of Primary Lung Cancer. Journal of the American College of Radiology : JACR Expert Panel on Thoracic Imaging:, de Groot, P. M., Chung, J. H., Ackman, J. B., Berry, M. F., Carter, B. W., Colletti, P. M., Hobbs, S. B., McComb, B. L., Movsas, B., Tong, B. C., Walker, C. M., Yom, S. S., Kanne, J. P. 2019; 16 (5S): S184–S195

    Abstract

    Lung cancer is the leading cause of cancer-related deaths in both men and women. The major risk factor for lung cancer is personal tobacco smoking, particularly for small-cell lung cancer (SCLC) and squamous cell lung cancers, but other significant risk factors include exposure to secondhand smoke, environmental radon, occupational exposures, and air pollution. Education and socioeconomic status affect both incidence and outcomes. Non-small-cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, comprises about 85% of lung cancers. SCLC accounts for approximately 13% to 15% of cases. Prognosis is directly related to stage at presentation. NSCLC is staged using the eighth edition of the tumor-node-metastasis (TNM) criteria of the American Joint Committee on Cancer. For SCLC the eighth edition of TNM staging is recommended to be used in conjunction with the modified Veterans Administration Lung Study Group classification system distinguishing limited stage from extensive stage SCLC. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

    View details for PubMedID 31054745

  • Adjuvant Therapy for Patients with Early Large Cell Lung Neuroendocrine Cancer: A National Analysis. The Annals of thoracic surgery Raman, V., Jawitz, O. K., Yang, C. J., Tong, B. C., D'Amico, T. A., Berry, M. F., Harpole, D. H. 2019

    Abstract

    BACKGROUND: Current guidelines do not routinely recommend adjuvant therapy for resected stage I large cell lung neuroendocrine cancer (LCNEC). However, data regarding the role of adjuvant therapy in early LCNEC are limited. This National Cancer Database (NCDB) analysis was performed to improve the evidence guiding adjuvant therapy for early LCNEC.METHODS: Overall survival (OS) of patients with pathologic T1-2aN0M0 LCNEC who underwent surgery in the NCDB from 2003 to 2015 was evaluated with Kaplan-Meier and multivariable Cox proportional hazards analyses. Patients who died within 30 days of surgery and with >R0 resection were excluded.RESULTS: Of 2642 patients meeting study criteria, 481 (18%) received adjuvant therapy. Adjuvant chemotherapy in stage IB patients was associated with a significant increase in OS (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.50, 0.90). However, there was no significant difference in survival between adjuvant chemotherapy and no adjuvant therapy for stage IA LCNEC (HR 0.92; 95%CI 0.75, 1.11). Adjuvant radiation, whether alone or in combination with chemotherapy, was not associated with a change in OS. In subgroup analysis, patients receiving adjuvant chemotherapy following lobar resection for stage IB LCNEC had a significant survival benefit compared to patients not receiving adjuvant therapy.CONCLUSIONS: In early stage LCNEC, adjuvant chemotherapy appears to confer an additional overall survival advantage only in patients with completely resected stage IB LCNEC and not for patients with completely resected stage IA LCNEC.

    View details for PubMedID 31004586

  • Right-Sided Versus Left-Sided Pneumonectomy After Induction Therapy for Non-Small Cell Lung Cancer ANNALS OF THORACIC SURGERY Yang, C., Shah, S. A., Lin, B. K., VanDusen, K. W., Chan, D. Y., Tan, W. D., Ranney, D. N., Cox, M. L., D'Amico, T. A., Berry, M. F. 2019; 107 (4): 1074-1081
  • A National Analysis of Short-term Outcomes and Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Clinical Stage II Non-Small-Cell Lung Cancer. Annals of surgery Yang, C. J., Kumar, A., Deng, J. Z., Raman, V., Lui, N. S., D'Amico, T. A., Berry, M. F. 2019

    Abstract

    MINI: In this national analysis, thoracoscopic lobectomy was associated with shorter hospital stay and no significant difference in long-term survival when compared to open lobectomy for cT1-2N1M0 non-small-cell lung cancer (NSCLC). These results suggest that thoracoscopic techniques are feasible in the treatment of stage II (cN1) NSCLC.OBJECTIVE: To compare outcomes after open versus thoracoscopic (VATS) lobectomy for clinical stage II (cN1) non-small-cell lung cancer (NSCLC).BACKGROUND: There have been no published studies evaluating the impact of a VATS approach to lobectomy for N1 NSCLC on short-term outcomes and survival.METHODS: Outcomes of patients with clinical T1-2, N1, M0 NSCLC who underwent lobectomy without induction therapy in the National Cancer Data Base (2010-2012) were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.RESULTS: Median follow-up of 1559 lobectomies (1204 open and 355 VATS) was 43.2 months. The VATS approach was associated with a shorter median hospitalization (5 vs 6 d, P < 0.001) than the open approach. There were no significant differences between the VATS and open approach with regard to nodal upstaging (12.0% vs 10.5%, P = 0.41), 30-day mortality (2.3% vs 3.1%, P = 0.31), and overall survival (5-yr survival: 48.6% vs 48.7%, P = 0.76; multivariable-adjusted HR for VATS approach: 1.08, 95% CI: 0.90-1.30, P = 0.39). A propensity score-matched analysis of 334 open and 334 VATS patients who were well matched by 14 common prognostic covariates, including tumor size, and comorbidities, continued to show no significant differences in nodal upstaging, 30-day mortality, and 5-year survival between the VATS and open groups.CONCLUSION: In this national analysis, VATS lobectomy was used in the minority of N1 NSCLC cases but was associated with shorter hospitalization and similar nodal upstaging rates, 30-day mortality, and long-term survival when compared to open lobectomy. These findings suggest thoracoscopic techniques are feasible for the treatment of stage II (cN1) NSCLC.

    View details for PubMedID 30946089

  • The influence of hormone replacement therapy on lung cancer incidence and mortality. The Journal of thoracic and cardiovascular surgery Titan, A. L., He, H. n., Lui, N. n., Liou, D. n., Berry, M. n., Shrager, J. B., Backhus, L. M. 2019

    Abstract

    Data regarding the effects of hormone replacement therapy (HRT) on non-small cell lung cancer (NSCLC) are mixed. We hypothesized HRT would have a protective benefit with reduced NSCLC incidence among women in a large, prospective cohort.We used data from the multicenter randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2001). Participants were women aged 50 to 74 years followed prospectively for up to 13 years for cancer screening. The influence of HRT on the primary outcome of NSCLC incidence and secondary outcomes of all-cause and disease-specific mortality were assessed with Kaplan-Meier analysis and Cox proportional hazard models adjusting for covariates.In the overall cohort of 75,587 women, 1147 women developed NSCLC after a median follow-up of 11.5 years. HRT use was characterized as 49.4% current users, 17.0% former users, and 33.6% never users. Increased age, smoking, comorbidities, and family history were associated with increased risk of NSCLC. On multivariable analysis, current HRT use was associated with reduced risk of NSCLC compared with never users (hazard ratio, 0.80; 95% confidence interval, 0.70-0.93; P = .009). HRT or oral contraception use was not associated with significant differences in all-cause mortality or disease-specific mortality.These data represent among the largest prospective cohorts suggesting HRT use may have a protective effect on the development of NSCLC among women; the physiological basis of this effect merits further study; however, the results may influence discussion surrounding HRT use in women.

    View details for DOI 10.1016/j.jtcvs.2019.10.070

    View details for PubMedID 31866083

  • Society for Translational Medicine Expert consensus on the selection of surgical approaches in the management of thoracic esophageal carcinoma JOURNAL OF THORACIC DISEASE Mao, Y., Yu, Z., You, B., Fang, W., Badgwell, B., Berry, M. F., Ceppa, D. P., Chen, C., Chen, H., Cuesta, M. A., D'Journo, X., Eslick, G. D., Fu, J., Fu, X., Gao, S., He, J., He, J., Huang, Y., Jiang, G., Jiang, Z., Kim, J. Y., Li, D., Li, H., Li, S., Liu, D., Liu, L., Liu, Y., Li, X., Li, Y., Mao, W., Molena, D., Morse, C. R., Novoa, N. M., Tan, L., Tan, Q., Toker, A., Tong, T., Wang, Q., Weksler, B., Xu, L., Xu, S., Yan, T., Zhang, L., Zhang, X., Zhang, X., Zhang, Z., Zhi, X., Zhou, Q. 2019; 11 (1): 319–28
  • ACR Appropriateness Criteria® Acute Respiratory Illness in Immunocompromised Patients. Journal of the American College of Radiology : JACR Lee, C. n., Colletti, P. M., Chung, J. H., Ackman, J. B., Berry, M. F., Carter, B. W., de Groot, P. M., Hobbs, S. B., Johnson, G. B., Maldonado, F. n., McComb, B. L., Tong, B. C., Walker, C. M., Kanne, J. P. 2019; 16 (11S): S331–S339

    Abstract

    The immunocompromised patient with an acute respiratory illness (ARI) may present with fever, chills, weight loss, cough, shortness of breath, or chest pain. The number of immunocompromised patients continues to rise with medical advances including solid organ and stem cell transplantation, chemotherapy, and immunomodulatory therapy, along with the continued presence of human immunodeficiency virus and acquired immunodeficiency syndrome. Given the myriad of pathogens that can infect immunocompromised individuals, identifying the specific organism or organisms causing the lung disease can be elusive. Moreover, immunocompromised patients often receive prophylactic or empiric antimicrobial therapy, further complicating diagnostic evaluation. Noninfectious causes for ARI should also be considered, including pulmonary edema, drug-induced lung disease, atelectasis, malignancy, radiation-induced lung disease, pulmonary hemorrhage, diffuse alveolar damage, organizing pneumonia, lung transplant rejection, and pulmonary thromboembolic disease. As many immunocompromised patients with ARI progress along a rapid and potentially fatal course, timely selection of appropriate imaging is of great importance in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking, or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

    View details for DOI 10.1016/j.jacr.2019.05.019

    View details for PubMedID 31685101

  • A Minimally Invasive Approach to Lobectomy After Induction Therapy Does Not Compromise Survival. The Annals of thoracic surgery Jeffrey Yang, C. F., Nwosu, A. n., Mayne, N. R., Wang, Y. Y., Raman, V. n., Meyerhoff, R. R., D'Amico, T. A., Berry, M. F. 2019

    Abstract

    The objective of this study was to evaluate the impact of a VATS approach on outcomes in patients who underwent lobectomy after induction therapy.Outcomes of patients with T2-T4, N0, M0 and T1-T4, N1-N2, M0 non-small-cell lung cancer (NSCLC) who received induction chemotherapy or chemoradiation followed by lobectomy in the National Cancer Data Base (NCDB) (2010-2014) were assessed using Kaplan-Meier, propensity score-matched, multivariable logistic regression and Cox proportional hazards analyses.In the NCDB, 2,887 lobectomy patients met inclusion criteria (VATS 676 [23%], Thoracotomy 2,211 [77%]). Of the VATS cases, patients who underwent induction chemoradiation were more likely to undergo conversion (aOR 1.70, p = 0.05). Compared to an open approach, VATS was associated with decreased length of stay (median: 5 days vs 6 days, P < 0.001) and no significant differences in 30-day mortality (VATS [1.5% (n=10)] vs open [2.6% (n=58)]; P=0.13) and 90-day mortality (VATS [3.7% (n=25)] vs open [5.6% (n=124)]; P=0.14). There were no significant differences in 5-year survival between the VATS and open groups in both the entire cohort (VATS [50.3%] vs open [52.3%]; P=0.83) and in a propensity score-matched analysis of 876 patients; furthermore, a VATS approach was also not associated with worse survival in multivariable analysis (HR = 1.02; 95% CI [0.86, 1.20]; P = 0.83).In this national analysis, a VATS approach for lobectomy in patients who received induction therapy for locally advanced NSCLC was not associated with worse short-term or long-term outcomes when compared to an open approach.

    View details for DOI 10.1016/j.athoracsur.2019.09.065

    View details for PubMedID 31733187

  • A national analysis of open versus minimally invasive thymectomy for stage I to III thymoma. The Journal of thoracic and cardiovascular surgery Yang, C. J., Hurd, J. n., Shah, S. A., Liou, D. n., Wang, H. n., Backhus, L. M., Lui, N. S., D'Amico, T. A., Shrager, J. B., Berry, M. F. 2019

    Abstract

    The oncologic efficacy of minimally invasive thymectomy for thymoma is not well characterized. We compared short-term outcomes and overall survival between open and minimally invasive (video-assisted thoracoscopic and robotic) approaches using the National Cancer Data Base.Perioperative outcomes and survival of patients who underwent open versus minimally invasive thymectomy for clinical stage I to III thymoma from 2010 to 2014 in the National Cancer Data Base were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. Predictors of minimally invasive use were evaluated using multivariable logistic regression. Outcomes of surgical approach were evaluated using an intent-to-treat analysis.Of the 1223 thymectomies that were evaluated, 317 (26%) were performed minimally invasively (141 video-assisted thoracoscopic and 176 robotic). The minimally invasive group had a shorter median length of stay when compared with the open group (3 [2-4] days vs 4 [3-6] days, P < .001). In a propensity score-matched analysis of 185 open and 185 minimally invasive (video-assisted thoracoscopic + robotic) thymectomy, the minimally invasive group continued to have a shorter median length of stay (3 vs 4 days, P < .01) but did not have significant differences in margin positivity (P = .84), 30-day readmission (P = .28), 30-day mortality (P = .60), and 5-year survival (89.4% vs 81.6%, P = .20) when compared with the open group.In this national analysis, minimally invasive thymectomy was associated with shorter length of stay and was not associated with increased margin positivity, perioperative mortality, 30-day readmission rate, or reduced overall survival when compared with open thymectomy.

    View details for DOI 10.1016/j.jtcvs.2019.11.114

    View details for PubMedID 32245668

  • A National Analysis of Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Stage I Non-small-cell Lung Cancer ANNALS OF SURGERY Yang, C., Kumar, A., Klapper, J. A., Hartwig, M. G., Tong, B. C., Harpole, D. H., Berry, M. F., D'Amico, T. A. 2019; 269 (1): 163–71
  • Impact of positive margins and radiation after tracheal adenoid cystic carcinoma resection on survival. The Annals of thoracic surgery Jeffrey Yang, C. F., Shah, S. n., Ramakrishnan, D. n., Raman, V. n., Diao, K. n., Wang, H. n., Commander, S. n., D'Amico, T. n., Berry, M. F. 2019

    Abstract

    Achieving negative margins for adenoid cystic carcinoma (ACC) of the trachea can be technically difficult. This study evaluated the impact of positive margins on prognosis and tested the hypothesis that radiation improves survival in the setting of incomplete resection.The impact of margin status and adjuvant therapy on overall survival of patients with tracheal ACC in the National Cancer Data Base (1998-2014) who underwent resection with known margin status and with no documented nodal or distant disease, was evaluated using Kaplan-Meier and Cox proportional hazard analysis.Of 132 patients who met study criteria, 79 (59.8%) had positive margins following resection. Adjuvant radiation was given to 95 (72.0%) patients overall and to 62 (78.5%) of the 79 patients with positive margins. The survival of patients with positive margins was not significantly different than the survival of patients with negative margins (5-year survival 82.2% [95% CI: 71.3-89.3] vs 82.0% [95% CI: 67.0-90.6], p=0.97), even after multivariable adjustment (HR, 1.73; 95% CI: 0.62-4.84; p=0.30). In the subset of patients with positive margins, there was no significant difference in survival between patients who did or did not receive postoperative radiation therapy (5-year survival: 82% [95% CI: 68.8-89.9] vs 82.4% [95% CI: 54.7-93.9], p=0.80), even after multivariable adjustment (HR, 1.04; 95% CI: 0.21-5.25; p=0.96).The majority of tracheal ACC resections performed in this national cohort had positive margins. Adjuvant radiation was commonly used for positive margins but was not associated with an overall survival benefit.

    View details for DOI 10.1016/j.athoracsur.2019.08.094

    View details for PubMedID 31589850

  • Society for Translational Medicine Expert consensus on the selection of surgical approaches in the management of thoracic esophageal carcinoma. Journal of thoracic disease Mao, Y., Yu, Z., You, B., Fang, W., Badgwell, B., Berry, M. F., Ceppa, D. P., Chen, C., Chen, H., Cuesta, M. A., D'Journo, X. B., Eslick, G. D., Fu, J., Fu, X., Gao, S., He, J., He, J., Huang, Y., Jiang, G., Jiang, Z., Kim, J. Y., Li, D., Li, H., Li, S., Liu, D., Liu, L., Liu, Y., Li, X., Li, Y., Mao, W., Molena, D., Morse, C. R., Novoa, N. M., Tan, L., Tan, Q., Toker, A., Tong, T., Wang, Q., Weksler, B., Xu, L., Xu, S., Yan, T., Zhang, L., Zhang, X., Zhang, X., Zhang, Z., Zhi, X., Zhou, Q. 2019; 11 (1): 319-328

    View details for DOI 10.21037/jtd.2018.12.07

    View details for PubMedID 30863610

    View details for PubMedCentralID PMC6384330

  • The role of thoracoscopic pneumonectomy in the management of non-small cell lung cancer: A multicenter study. The Journal of thoracic and cardiovascular surgery Yang, C. J., Yendamuri, S., Mayne, N. R., Battoo, A., Wang, H., Meyerhoff, R. R., Vandusen, K., Hirji, S. A., Berry, M. F., McKenna, R. J., Demmy, T. L., D'Amico, T. A. 2018

    Abstract

    OBJECTIVE: The objective of this study was to evaluate the impact of the video-assisted thoracoscopic (VATS) approach on the outcomes of patients who underwent pneumonectomy.METHODS: The effect of the surgical approach on perioperative complications and survival in patients who underwent pneumonectomy for nonmetastatic non-small cell lung cancer across 3 institutions (2000-2016) was assessed using multivariable logistic regression, Cox proportional hazards analysis, and propensity-score matching. Completion pneumonectomies were excluded from this study, and an "intent-to-treat" analysis was performed.RESULTS: During the study period, 359 patients met inclusion criteria and underwent pneumonectomy for nonmetastatic non-small cell lung cancer; 124 (35%) underwent pneumonectomy via VATS and 235 (65%) via thoracotomy. Perioperative mortality (VATS, 7% [n = 9] vs open, 8% [n = 19]; P = .75) and morbidity (VATS, 28% [n = 35] vs open, 28% [n = 65]; P = .91) were similar between the groups, even after multivariable adjustment. VATS showed similar 5-year survival when compared with thoracotomy in unadjusted analysis (47% [95% confidence interval (CI), 36-56] vs 33% [95% CI, 27-40]; P=.19), even after multivariable adjustment (hazard ratio, 0.76 [95% CI, 0.50-1.18]; P=.23). In a propensity score-matched analysis that balanced patient characteristics, there were no significant differences found in overall survival between the 2 groups (P=.69).CONCLUSIONS: Although the role of VATS pneumonectomy will likely become clearer as more surgeons report results, this multicenter study suggests that the VATS approach for pneumonectomy can be performed safely, with at least equivalent oncologic outcomes when compared with thoracotomy.

    View details for PubMedID 30739773

  • The impact of postoperative therapy on primary cardiac sarcoma. The Journal of thoracic and cardiovascular surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018; 156 (6): 2194-2203

    Abstract

    Primary cardiac sarcomas (PCS) are extremely rare, portend a very poor prognosis, and have limited outcomes data to direct management. This study evaluated the impact of postoperative chemotherapy and/or radiotherapy on survival for PCS.A retrospective chart review was conducted of 12 patients diagnosed with and who underwent resection for PCS at a single institution between 2000 and 2016. Data were collected on patient/tumor characteristics and analyzed with respect to treatment and outcome using Kaplan-Meier methods.Median age was 43 (range 21-73 years) with a 50:50 male-to-female ratio. The most common subtype was angiosarcoma (42%), and 25% presented with distant metastases (DMs). The initial treatment modality for all patients was surgery, with 58% having macroscopically positive (R2) margins. In total, 75% received postoperative chemotherapy and/or radiotherapy. Median progression-free survival (PFS) was 5.9 months, and median overall survival (OS) was 12.0 months. Achieving negative or microscopically positive margins (R0/R1) as compared with R2 resection significantly improved PFS (12.6 vs 2.7 months, P = .008) and OS (21.8 vs 7.2 months, P = .006). DM at presentation demonstrated a significantly shorter OS (7.0 vs 16.9 months, P = .04) and PFS (0.7 vs 7.9 months, P = .003) compared with localized disease. Patients given postoperative therapy had longer OS compared with surgery only, but this difference was not statistically significant (15.5 vs 2.6 months, P = .12).Gross total surgical resection can significantly improve PFS and OS in PCS, but DM at diagnosis is an extremely poor prognostic sign. Postoperative therapy should be considered, although this study was likely underpowered to demonstrate a statistically significant benefit.

    View details for DOI 10.1016/j.jtcvs.2018.04.127

    View details for PubMedID 30454911

  • Long-term Survival After Surgery Compared With Concurrent Chemoradiation for Node-negative Small Cell Lung Cancer ANNALS OF SURGERY Yang, C., Chan, D. Y., Shah, S. A., Yemkun, B. A., Wang, X. F., D'Amico, T. A., Berry, M. F., Harpole Jr, D. H. 2018; 268 (6): 1105-1112
  • Right-sided vs Left-sided Pneumonectomy after Induction Therapy for Non-small-cell Lung Cancer. The Annals of thoracic surgery Yang, C. J., Shah, S., Lin, B. K., Vandusen, K., Chan, D. Y., Tan, W., Ranney, D., Cox, M., D'Amico, T. A., Berry, M. F. 2018

    Abstract

    BACKGROUND: A right-sided pneumonectomy after induction therapy for non-small-cell lung cancer (NSCLC) has been shown to be associated with significant perioperative risk. We examined the impact of laterality on long-term survival after induction therapy and pneumonectomy using the National Cancer Data Base (NCDB).METHODS: Perioperative and long-term outcomes of patients who underwent pneumonectomy following induction chemotherapy with or without radiation from 2004-2014 in the NCDB were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.RESULTS: During the study period, 1465 patients (right n=693 [47.3%], left n=772 [52.7%]) met inclusion criteria. Right-sided pneumonectomy was associated with significantly higher 30-day (8.2% [57/693] vs 4.2% [32/772], p< 0.01) and 90-day mortality (13.6% [94/693] vs 7.9% [61/772], p<0.01), and right-sided pneumonectomy was a predictor of higher 90-day mortality (OR 2.23, p<0.01). However, overall survival between right and left pneumonectomy was not significantly different in univariate (5-year survival 37.6% [95% CI: 0.34-0.42] vs 35% [95% CI: 0.32-0.39], log-rank p=0.94) or multivariable analysis (hazard ratio, 1.07 [95% CI: 0.92-1.25], p=0.40). In a propensity score-matched analysis of 810 patients, there were no significant differences in 5-year survival between the right- vs left-sided groups (34.7% [95% CI: 0.30-0.40] vs 34.1%, [95% CI: 0.29-0.39], log-rank p =0.86).CONCLUSIONS: In this national analysis, right-sided pneumonectomy after induction therapy was associated with a significantly higher perioperative but not worse long-term mortality compared to a left-sided procedure.

    View details for PubMedID 30448482

  • Response to: "Comment on: A National Analysis of Longterm Survival Following Thoracoscopic Versus Open Lobectomy for Stage I Nonsmallcell Lung Cancer". Annals of surgery Yang, C. J., Kumar, A., Berry, M. F., D'Amico, T. A. 2018

    View details for PubMedID 30407205

  • Society for Translational Medicine expert consensus on training and certification standards for surgeons and assistants in minimally invasive surgery for lung cancer. Journal of thoracic disease Liu, L., Mei, J., He, J., Gao, S., Li, S., He, J., Huang, Y., Xu, S., Mao, W., Tan, Q., Chen, C., Li, X., Zhang, Z., Jiang, G., Xu, L., Zhang, L., Fu, J., Li, H., Wang, Q., Liu, D., Tan, L., Zhou, Q., Fu, X., Jiang, Z., Chen, H., Fang, W., Zhang, X., Li, Y., Tong, T., Yu, Z., Liu, Y., Zhi, X., Yan, T., Zhang, X., Demmy, T. L., Berry, M. F., Gutierrez Pérez, A. B., Cataneo, D., Bille, A., Licht, P., Kocher, G. J., Oncel, M., Evman, S., Jensen, K., Bagan, P., Embun, R. 2018; 10 (10): 5666-5672

    View details for DOI 10.21037/jtd.2018.08.72

    View details for PubMedID 30505474

    View details for PubMedCentralID PMC6236169

  • Examination of Optimal Timing of Post-Surgical Surveillance for Early Stage Lung Cancer Patients and Association with Outcomes Colwell, E., Bhandari, P., Benson, J., He, H., Lui, N., Berry, M., Shrager, J., Backhus, L. ELSEVIER SCIENCE INC. 2018: S819
  • The Role of Adjuvant Therapy for Patients with Early Stage Large Cell Neuroendocrine Lung Cancer: A National Analysis Raman, V., Yang, C., Jawitz, O., Erkmen, C., Tong, B., D'Amico, T., Berry, M., Harpole, D. ELSEVIER SCIENCE INC. 2018: S648
  • Factors Associated With Treatment of Clinical Stage I Non-Small-cell Lung Cancer: A Population-based Analysis. Clinical lung cancer Berry, M. F., Canchola, A. J., Gensheimer, M. F., Gomez, S. L., Cheng, I. 2018; 19 (5): e745–e758

    Abstract

    BACKGROUND: The present study examined clinical stage I non-small-cell lung cancer (NSCLC) treatment in the population-based California Cancer Registry.PATIENTS AND METHODS: The characteristics associated with first clinical stage I NSCLC treatment (surgery, radiation, no local therapy) from 2003 to 2014 were identified using logistic regression. Survival was evaluated using Kaplan-Meier and Cox proportional hazard analyses.RESULTS: Surgery was used in most patients who met the inclusion criteria (14,545 of 19,893; 73.1%), although relatively similar numbers had undergone radiation (n= 2848; 14.3%) or not received therapy (n= 2500; 12.6%). Surgery use ranged from 68.5% to 77.2% patients annually. The percentage of patients with no therapy decreased from 18.1% (315 of 1737) in 2003 to 10.3% (176 of 1703) in 2014, and radiation use increased from 10.7% (185 of 1737) in 2003 to 21.2% (361 of 1703) in 2014. Patients who did not receive therapy were more likely to be older, not white, male, and unmarried, to have no insurance or public insurance other than Medicare, to live in a lower socioeconomic status neighborhood, to have been seen at a non-National Cancer Institute cancer center hospital or hospital serving lower socioeconomic status patients, and to have larger tumors. The 5-year all-cause survival after no therapy (12.7%) was significantly worse than that after surgery (64.9%) or radiation (21.5%; P< .0001).CONCLUSION: In the present population-based analysis, surgery was the most common treatment for clinical stage I NSCLC but was not used for almost 27% of patients. Radiation use increased and the proportion of patients who did not receive any therapy decreased over time.

    View details for PubMedID 30149883

  • Factors Associated With Treatment of Clinical Stage I Non-Small-cell Lung Cancer: A Population-based Analysis CLINICAL LUNG CANCER Berry, M. F., Canchola, A. J., Gensheimer, M. F., Gomez, S. L., Cheng, I. 2018; 19 (5): E745–E758
  • ALL EVIDENCE POINTS TO THE NEED FOR COLLABORATIVE CARE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yerokun, B. A., Berry, M. F., Hartwig, M. G. 2018; 156 (2): 820–21

    View details for PubMedID 30011771

  • Computed Tomography Features associated With the Eighth Edition TNM Stage Classification for Thymic Epithelial Tumors JOURNAL OF THORACIC IMAGING Padda, S. K., Terrone, D., Tian, L., Khuong, A., Neal, J. W., Riess, J. W., Berry, M. F., Hoang, C. D., Burt, B. M., Leung, A. N., Schwartz, E. J., Shrager, J. B., Wakelee, H. A. 2018; 33 (3): 176–83

    Abstract

    The eighth edition of the TNM classification of malignant tumors for the first time includes an official staging system for thymic epithelial tumors (TETs) recognized by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC). Staging is critical for the management of TETs, and determining stage accurately from imaging has the potential to improve clinical outcomes. We examine preoperative computed tomography (CT) characteristics of TETs associated with AJCC/UICC pathologic TNM stage.In this retrospective study, patients were included if they met all the following criteria: (1) diagnosis of TET, (2) had primary curative intent surgery performed at Stanford University, and (3) had available preoperative CT imaging for review. Tumor pathology was staged according to the eighth edition TNM classification. Fifteen CT scan features were examined from each patient case according to the International Thymic Malignancy Interest Group standard report terms in a blinded manner. A Lasso-regularized multivariate model was used to produce a weighted scoring system predictive of pathologic TNM stage.Examining the 54 patients included, the following CT characteristics were associated with higher pathologic TNM stage when using the following scoring system: elevated hemidiaphragm (score of 6), vascular endoluminal invasion (score of 6), pleural nodule (score of 2), lobulated contour (score of 2), and heterogeneous internal density (score of 1). Area under the receiver operating characteristic curve was 0.76.TETs with clearly invasive or metastatic features seen on CT are associated with having higher AJCC/UICC pathologic TNM stage, as expected. However, features of lobulated contour and heterogeneous internal density are also associated with higher stage disease. These findings need to be validated in an independent cohort.

    View details for PubMedID 29219888

  • Intraoperative costs of video-assisted thoracoscopic lobectomy can be dramatically reduced without compromising outcomes JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Richardson, M. T., Backhus, L. M., Berry, M. F., Vail, D. G., Ayers, K. C., Benson, J. A., Bhandari, P., Teymourtash, M., Shrager, J. B. 2018; 155 (3): 1267-+

    Abstract

    To determine whether surgeon selection of instrumentation and other supplies during video-assisted thoracoscopic lobectomy (VATSL) can safely reduce intraoperative costs.In this retrospective, cost-focused review of all video-assisted thoracoscopic surgery anatomic lung resections performed by 2 surgeons at a single institution between 2010 and 2014, we compared VATSL hospital costs and perioperative outcomes between the surgeons, as well as costs of VATSL compared with thoracotomy lobectomy (THORL).A total of 100 VATSLs were performed by surgeon A, and 70 were performed by surgeon B. The preoperative risk factors did not differ significantly between the 2 groups of surgeries. Mean VATSL total hospital costs per case were 24% percent greater for surgeon A compared with surgeon B (P = .0026). Intraoperative supply costs accounted for most of this cost difference and were 85% greater for surgeon A compared with surgeon B (P < .0001). The use of nonstapler supplies, including energy devices, sealants, and disposables, drove intraoperative costs, accounting for 55% of the difference in intraoperative supply costs between the surgeons. Operative time was 25% longer for surgeon A compared with surgeon B (P < .0001), but this accounted for only 11% of the difference in total cost. Surgeon A's overall VATSL costs per case were similar to those of THORLs (n = 100) performed over the same time period, whereas surgeon B's VATSL costs per case were 24% less than those of THORLs. On adjusted analysis, there was no difference in VATSL perioperative outcomes between the 2 surgeons.The costs of VATSL differ substantially among surgeons and are heavily influenced by the use of disposable equipment/devices. Surgeons can substantially reduce the costs of VATSL to far lower than those of THORL without compromising surgical outcomes through prudent use of costly instruments and technologies.

    View details for PubMedID 29224839

  • Survival after radiation for stage I and II non-small cell lung cancer with positive margins JOURNAL OF SURGICAL RESEARCH Gulack, B. C., Cox, M. L., Yang, C., Speicher, P. J., Kara, H., D'Amico, T. A., Berry, M. F., Hartwig, M. G. 2018; 223: 94–101

    Abstract

    There is limited data guiding treatment for positive margins following lobectomy for early-stage non-small cell lung cancer (NSCLC). Using data from the National Cancer Data Base, we sought to determine whether radiation therapy following lobectomy for stage I or II NSCLC was associated with improved overall survival in patients with positive margins.Patients who underwent lobectomy without induction therapy for stage I or II NSCLC (1998-2006) with positive resection margins were selected. Patients were stratified by administration of radiation therapy following surgery, and overall survival was estimated using the Kaplan-Meier method. The association between radiation therapy and survival was adjusted for nonrandom treatment selection using Cox proportional hazards regression modeling.Positive margins were recorded in 1934 of 49,563 (3.9%) patients who underwent lobectomy for stage I or II NSCLC. Positive margin status was associated with significantly worse 5-year survival (34.5% versus 57.2%, P < 0.001). After selection of patients with positive margins and known radiation status and exclusion of patients who had upstaged disease or received radiation therapy for palliative indications, radiation therapy was used in 579 of 1579 patients (38.2%) but was not associated with a significant difference in the likelihood of death during subsequent follow-up (hazard ratio: 1.10, 95% confidence interval: 0.90, 1.35).Positive margins following lobectomy for stage I or II NSCLC are associated with reduced 5-year survival. Postsurgical radiation is not strongly associated with an improvement in overall survival among these patients.

    View details for PubMedID 29433891

  • Surgical Outcomes After Neoadjuvant Chemotherapy and Ipilimumab for Non-Small Cell Lung Cancer ANNALS OF THORACIC SURGERY Yang, C., Mayne, N. R., Wang, X., Berry, M. F., Tong, B., Harpole, D. H., D'Amico, T. A., Christensen, J. D., Ready, N. E., Klapper, J. A. 2018; 105 (3): 924–29

    Abstract

    The objective of this study was to evaluate the safety and feasibility of using neoadjuvant chemotherapy plus ipilimumab followed by surgery as a treatment strategy for stage II-IIIA non-small cell lung cancer.From 2013 to 2017, postoperative data from patients who underwent surgery after neoadjuvant chemotherapy plus ipilimumab in the TOP1201 trial, an open label phase II trial (NCT01820754), were prospectively collected. The surgical outcomes from TOP1201 were compared with outcomes in a historical cohort of patients receiving standard preoperative chemotherapy followed by surgery identified from our institution's prospectively collected thoracic surgery database.In the TOP1201 trial, 13 patients were treated with preoperative chemotherapy and ipilimumab followed by surgery. In the historical cohort, 42 patients received preoperative chemotherapy by a platinum doublet regimen preoperative chemotherapy by a platinum doublet regimen without ipilimumab followed by lobectomy or pneumonectomy. The 30-day mortality in both groups was 0%. The most frequently occurring perioperative complications in the TOP1201 group were prolonged air leak (n = 2, 15%) and urinary tract infection (n = 2, 15%). The most common perioperative complication in the preoperative chemotherapy alone group was atrial fibrillation (n = 6, 14%). One patient (8%) had atrial fibrillation in the TOP1201 group. There was no apparent increased occurrence of adverse surgical outcomes for patients in the TOP1201 group compared with patients receiving standard of care neoadjuvant chemotherapy alone before surgery for stage II-IIIA non-small cell lung cancer.This report is the first to demonstrate the safety and feasibility of surgical resection after treatment with ipilimumab and chemotherapy in stage II-IIIA non-small-cell lung cancer.

    View details for PubMedID 29258674

  • Induction therapy for locally advanced distal esophageal adenocarcinoma: Is radiation Always necessary? The Journal of thoracic and cardiovascular surgery Liou, D. Z., Backhus, L. M., Lui, N. S., Shrager, J. B., Berry, M. F. 2018

    Abstract

    OBJECTIVE: To compare outcomes between induction chemotherapy alone (ICA) and induction chemoradiation (ICR) in patients with locally advanced distal esophageal adenocarcinoma.METHODS: Patients in the National Cancer Database treated with ICA or ICR followed by esophagectomy between 2006 and 2012 for cT1-3N1M0 or T3N0M0 adenocarcinoma of the distal esophagus were compared using logistic regression, Kaplan-Meier analysis, and Cox proportional hazards methods.RESULTS: The study group included 4763 patients, of whom 4323 patients (90.8%) received ICR and 440 patients (9.2%) received ICA. There were no differences in age, sex, race, Charlson Comorbidity Index, treatment facility type, clinical T or N status between the 2 groups. Tumor size ≥5cm (odds ratio, 1.46; P=.006) was the only factor that predicted ICR use. Higher rates of T downstaging (39.7% vs 33.4%; P=.012), N downstaging (32.0% vs 23.4%; P<.001), and complete pathologic response (13.1% vs 5.9%; P<.001) occurred in ICR patients. Positive margins were seen more often in ICA patients (9.6% vs 5.5%; P=.001), but there was no difference in 5-year survival (ICR 35.9% vs ICA 37.2%; P=.33), and ICR was not associated with survival in multivariable analysis (hazard ratio=1.04; P=.61).CONCLUSIONS: ICR for locally advanced distal esophageal adenocarcinoma is associated with a better local treatment effect, but not improved survival compared with ICA, which suggests that radiation can be used selectively in this clinical situation.

    View details for PubMedID 29530567

  • Thoracic Surgery Considerations in Obese Patients THORACIC SURGERY CLINICS Liou, D. Z., Berry, M. F. 2018; 28 (1): 27-+

    Abstract

    The obesity epidemic in the United States has increased greatly over the past several decades, and thoracic surgeons are likely to see obese patients routinely in their practices. Obesity has direct deleterious health effects such as metabolic disorder and cardiovascular disease, and is associated with many cancers. Obese patients who need thoracic surgery pose practical challenges to many of the routine elements in perioperative management. Preoperative assessment of obesity-related comorbid conditions and risk stratification for surgery, thorough intraoperative planning for anesthesia and surgery, and postoperative strategies to optimize pulmonary hygiene and mobility minimize the risk of adverse outcomes.

    View details for PubMedID 29150035

  • Presence of Even a Small Ground-Glass Component in Lung Adenocarcinoma Predicts Better Survival CLINICAL LUNG CANCER Berry, M. F., Gao, R., Kunder, C. A., Backhus, L., Khuong, A., Kadoch, M., Leung, A., Shrager, J. 2018; 19 (1): E47–E51

    Abstract

    While lepidic-predominant lung adenocarcinomas are known to have better outcomes than similarly sized solid tumors, the impact of smaller noninvasive foci within predominantly solid tumors is less clearly characterized. We tested the hypothesis that lung adenocarcinomas with even a small ground-glass opacity (GGO) component have a better prognosis than otherwise similar pure solid (PS) adenocarcinomas.The maximum total and solid-component diameters were determined by preoperative computed tomography in patients who underwent lobar or sublobar resection of clinical N0 adenocarcinomas without induction therapy between May 2003 and August 2013. Survival between patients with PS tumors (0% GGO) or tumors with a minor ground-glass (MGG) component (1%-25% GGO) was compared by Kaplan-Meier and Cox analyses.A total of 123 patients met the inclusion criteria, comprising 54 PS (44%) and 69 MGG (56%) whose mean ground-glass component was 18 ± 7%. The solid component tumor diameter was not significantly different between the groups (2.3 ± 1.2 cm vs. 2.5 ± 1.3 cm, P = .2). Upstaging to pN1-2 was more common for the PS group (13% [7/54] vs. 3% [2/69], P = .04), but the distribution of pathologic stage was not significantly different between the groups (PS 76% stage I [41/54] vs. MGG 80% stage I [55/69], P = .1). Having a MGG component was associated with markedly better survival in both univariate analysis (MGG 5-year overall survival 86.7% vs. PS 64.5%, P = .001) and multivariable survival analysis (hazard ratio, 0.30, P = .01).Patients with resected cN0 lung adenocarcinoma who have even a small GGO component have markedly better survival than patients with PS tumors, which may have implications for both treatment and surveillance strategies.

    View details for PubMedID 28743420

  • Long-term outcomes of surgical resection for stage IV non-small-cell lung cancer: A national analysis LUNG CANCER Yang, C., Gu, L., Shah, S. A., Yerokun, B. A., D'Amico, T. A., Hartwig, M. G., Berry, M. F. 2018; 115: 75–83

    Abstract

    Treatment guidelines recommend surgical resection in select cases of stage IV non-small-cell lung cancer (NSCLC) but are based on limited evidence. This study evaluated outcomes associated with surgery in stage IV disease.Factors associated with survival of stage IV NSCLC patients treated with surgery in the National Cancer Date Base (2004-2013) were evaluated using multivariable Cox proportional hazards analyses. Outcomes of the subset of patients with cT1-2, N0-1, M1 and cT3, N0, M1 disease treated with surgery or chemoradiation were evaluated using Kaplan-Meier analyses.The five-year survival of all stage IV NSCLC patients who underwent surgical resection (n=3098) was 21.1%. Outcomes were related to the locoregional extent of the primary tumor, as both increasing T status (T2 HR 1.30 [p<0.001], T3 HR 1.28 [p<0.001], and T4 HR 1.28 [p<0.001], respectively, compared to T1) and nodal involvement (N1 HR 1.34 [p<0.001], N2 HR 1.50 [p<0.001], and N3 HR 1.49 [p<0.001], respectively, compared to N0) were associated with worse survival. Outcomes were also related to the extent of surgical resection, as pneumonectomy (HR 1.58, p<0.001), segmentectomy (HR 1.36, p=0.009), and wedge resection (HR 1.70, p<0.001) were all associated with decreased survival when compared to lobectomy. The five-year survival of cT1-2, N0-1, M1 and cT3, N0, M1 patients was 25.1% (95% CI: 22.8-27.5) after surgical resection (n=1761) and 5.8% (95% CI: 5.2-6.5) after chemoradiation (n=8180).Surgery for cT1-2, N0-1, M1 or cT3, N0, M1 disease is associated with a 5-year survival of 25% and does not appear to compromise outcomes when compared to non-operative therapy, supporting guidelines that recommend surgery for very select patients with stage IV disease. However, surgery provides less benefit and should be considered much less often for stage IV patients with mediastinal nodal disease or more locally advanced tumors.

    View details for PubMedID 29290266

  • The Impact of Post-Operative Therapy on Primary Cardiac Sarcoma The Journal of Thoracic and Cardiovascular Surgery Wu, Y., Million, L., Moding, E. J., Scott, G., Berry, M., Ganjoo, K. N. 2018
  • Genomic Profiling of Bronchoalveolar Lavage Fluid in Patients with Non-Small Cell Lung Cancer Nair, V. S., Li, A., Stehr, H., Chabon, J., Chaudhuri, A., Zhou, L., Naemi, H., Ayers, K., Ramsey, M., Bedi, H. S., Van Wert, R., Sung, A. W., Lui, N., Backhus, L., Berry, M., Shrager, J. B., Alizadeh, A., Diehn, M. AMER THORACIC SOC. 2018
  • Immune Activation in Early-Stage Non-Small Cell Lung Cancer Patients Receiving Neoadjuvant Chemotherapy Plus Ipilimumab. Clinical cancer research : an official journal of the American Association for Cancer Research Yi, J. S., Ready, N., Healy, P., Dumbauld, C., Osborne, R., Berry, M., Shoemaker, D., Clarke, J., Crawford, J., Tong, B., Harpole, D., D'Amico, T. A., McSherry, F., Dunphy, F., McCall, S. J., Christensen, J. D., Wang, X., Weinhold, K. J. 2017; 23 (24): 7474-7482

    Abstract

    Purpose: To determine the immunologic effects of neoadjuvant chemotherapy plus ipilimumab in early-stage non-small cell lung cancer (NSCLC) patients.Experimental Design: This is a single-arm chemotherapy plus phased ipilimumab phase II study of 24 treatment-naïve patients with stage IB-IIIA NSCLC. Patients received neoadjuvant therapy consisting of 3 cycles of paclitaxel with either cisplatin or carboplatin and ipilimumab included in the last 2 cycles.Results: Chemotherapy alone had little effect on immune parameters in PBMCs. Profound CD28-dependent activation of both CD4 and CD8 cells was observed following ipilimumab. Significant increases in the frequencies of CD4+ cells expressing activation markers ICOS, HLA-DR, CTLA-4, and PD-1 were apparent. Likewise, increased frequencies of CD8+ cells expressing the same activation markers, with the exception of PD-1, were observed. We also examined 7 resected tumors and found higher frequencies of activated tumor-infiltrating lymphocytes than those observed in PBMCs. Surprisingly, we found 4 cases of preexisting tumor-associated antigens (TAA) responses against survivin, PRAME, or MAGE-A3 present in PBMC at baseline, but neither increased frequencies nor the appearance of newly detectable responses following ipilimumab therapy. Ipilimumab had little effect on the frequencies of circulating regulatory T cells and MDSCs.Conclusions: This study did not meet the primary endpoint of detecting an increase in blood-based TAA T-cell responses after ipilimumab. Collectively, these results highlight the immune activating properties of ipilimumab in early-stage NSCLC. The immune profiling data for ipilimumab alone can contribute to the interpretation of immunologic data from combined immune checkpoint blockade immunotherapies. Clin Cancer Res; 23(24); 7474-82. ©2017 AACR.

    View details for DOI 10.1158/1078-0432.CCR-17-2005

    View details for PubMedID 28951518

    View details for PubMedCentralID PMC5732888

  • Impact of Timing of Lobectomy on Survival for Clinical Stage IA Lung Squamous Cell Carcinoma CHEST Yang, C., Wang, H., Kumar, A., Wang, X., Hartwig, M. G., D'Amico, T. A., Berry, M. F. 2017; 152 (6): 1239–50

    Abstract

    Because the relationship between the timing of surgery following diagnosis of lung cancer and survival has not been precisely described, guidelines on what constitutes a clinically meaningful delay of resection of early-stage lung cancer do not exist. This study tested the hypothesis that increasing the time between diagnosis and lobectomy for stage IA squamous cell carcinoma (SCC) would be associated with worse survival.The association between timing of lobectomy and survival for patients with clinical stage IA SCC in the National Cancer Data Base (2006-2011) was assessed using multivariable Cox proportional hazards analysis and restricted cubic spline (RCS) functions.The 5-year overall survival of 4,984 patients who met study inclusion criteria was 58.3% (95% CI, 56.3-60.2). Surgery was performed within 30 days of diagnosis in 1,811 (36%) patients, whereas the median time to surgery was 38 days (interquartile range, 23, 58). In multivariable analysis, patients who had surgery 38 days or more after diagnosis had significantly worse 5-year survival than patients who had surgery earlier (hazard ratio, 1.13 [95% CI, 1.02-1.25]; P = .022). Multivariable RCS analysis demonstrated the hazard ratio associated with time to surgery increased steadily the longer resection was delayed; the threshold time associated with statistically significant worse survival was ∼90 days or greater.Longer intervals between diagnosis of early-stage lung SCC and surgery are associated with worse survival. Although factors other than the timing of treatment may contribute to this finding, these results suggest that efforts to minimize delays beyond those needed to perform a complete preoperative evaluation may improve survival.

    View details for PubMedID 28800867

  • A National Analysis of Long-term Survival Following Thoracoscopic Versus Open Lobectomy for Stage I Non-small-cell Lung Cancer. Annals of surgery Yang, C. J., Kumar, A., Klapper, J. A., Hartwig, M. G., Tong, B. C., Harpole, D. H., Berry, M. F., D'Amico, T. A. 2017

    Abstract

    OBJECTIVE: The objective of this study was to compare the long-term survival of open versus thoracoscopic (VATS) lobectomy for early stage non-small-cell lung cancer (NSCLC).BACKGROUND: Data from national studies on long-term survival for VATS versus open lobectomy are limited.METHODS: Outcomes of patients who underwent open versus VATS lobectomy for clinical T1-2, N0, M0 NSCLC in the National Cancer Data Base were evaluated using propensity score matching.RESULTS: The median follow-up of 7114 lobectomies (5566 open and 1548 VATS) was 52.0 months. Propensity score matching resulted in 1464 open and 1464 VATS patients who were well-matched by 14 common prognostic covariates including tumor size and comorbidities. The VATS approach was associated with a shorter median length of stay (5 vs. 6 days, P < 0.001) and better 5-year survival (66.0% vs. 62.5%, P = 0.026), and was not significantly different compared with the open approach with regard to nodal upstaging (11.2% vs. 12.5%, P = 0.46), and 30-day mortality (1.7% vs. 2.5%, P = 0.14). In the propensity-matched analysis of 2928 patients, there were no significant differences in 5-year survival between the VATS and open groups (66.3% vs. 65.8%, P = 0.92).CONCLUSIONS: In this national analysis, VATS lobectomy was used in the minority of patients with stage I NSCLC. VATS lobectomy was associated with shorter length of stay and noninferior long-term survival when compared with open lobectomy. These results support previous findings from smaller single- and multi-institutional studies that suggest that VATS does not compromise oncologic outcomes when used for early-stage lung cancer and suggest the need for broader implementation of VATS techniques.

    View details for PubMedID 28799982

  • Reporting and Guidelines in Propensity Score Analysis: A Systematic Review of Cancer and Cancer Surgical Studies. Journal of the National Cancer Institute Yao, X. I., Wang, X., Speicher, P. J., Hwang, E. S., Cheng, P., Harpole, D. H., Berry, M. F., Schrag, D., Pang, H. H. 2017; 109 (8)

    Abstract

    : Propensity score (PS) analysis is increasingly being used in observational studies, especially in some cancer studies where random assignment is not feasible. This systematic review evaluates the use and reporting quality of PS analysis in oncology studies.: We searched PubMed to identify the use of PS methods in cancer studies (CS) and cancer surgical studies (CSS) in major medical, cancer, and surgical journals over time and critically evaluated 33 CS published in top medical and cancer journals in 2014 and 2015 and 306 CSS published up to November 26, 2015, without earlier date limits. The quality of reporting in PS analysis was evaluated. It was also compared over time and among journals with differing impact factors. All statistical tests were two-sided.More than 50% of the publications with PS analysis from the past decade occurred within the past two years. Of the studies critically evaluated, a considerable proportion did not clearly provide the variables used to estimate PS (CS 12.1%, CSS 8.8%), incorrectly included non baseline variables (CS 3.4%, CSS 9.3%), neglected the comparison of baseline characteristics (CS 21.9%, CSS 15.6%), or did not report the matching algorithm utilized (CS 19.0%, CSS 36.1%). In CSS, the reporting of the matching algorithm improved in 2014 and 2015 ( P  = .04), and the reporting of variables used to estimate PS was better in top surgery journals ( P  = .008). However, there were no statistically significant differences for the inclusion of non baseline variables and reporting of comparability of baseline characteristics.The use of PS in cancer studies has dramatically increased recently, but there is substantial room for improvement in the quality of reporting even in top journals. Herein we have proposed reporting guidelines for PS analyses that are broadly applicable to different areas of medical research that will allow better evaluation and comparison across studies applying this approach.

    View details for DOI 10.1093/jnci/djw323

    View details for PubMedID 28376195

  • Surgery Versus Optimal Medical Management for N1 Small Cell Lung Cancer. Annals of thoracic surgery Yang, C. J., Chan, D. Y., Speicher, P. J., Gulack, B. C., Tong, B. C., Hartwig, M. G., Kelsey, C. R., D'Amico, T. A., Berry, M. F., Harpole, D. H. 2017; 103 (6): 1767-1772

    Abstract

    Adjuvant chemotherapy has been demonstrated to improve the outcomes of patients with N1 non-small cell lung cancer. It is unknown whether patients previously thought to have unresectable small cell lung cancer (SCLC) may have tumors amenable to surgery if adjuvant therapies can be given. This study was undertaken to evaluate whether surgery, in the setting of modern adjuvant therapies, can be beneficial for patients with N1-positive SCLC.Patients with clinical T1-3 N1 M0 SCLC who underwent concurrent chemoradiation versus surgery and adjuvant therapy in the National Cancer Data Base from 2003 to 2011 were examined. Overall survival was assessed using Kaplan-Meier and Cox proportional hazards analysis and propensity score-matched analysis.Of 1,041 patients with cT1-3 N1 M0 SCLC who met inclusion criteria, 96 patients (9%) underwent surgery and adjuvant chemotherapy with or without radiation and 945 (91%) underwent concurrent chemoradiation alone. Multivariable Cox modeling demonstrated that surgery with adjuvant chemotherapy with or without radiation (hazard ratio 0.74, 95% confidence interval: 0.56 to 0.97) was associated with improved survival compared with concurrent chemoradiation. After propensity matching, surgery with adjuvant chemotherapy with or without radiation was associated with improved 5-year survival compared with concurrent chemoradiation (31.4% versus 26.3%).In an analysis of a national population-based cancer database, surgery followed by adjuvant chemotherapy with or without radiation for cT1-3 N1 SCLC had improved outcomes compared with concurrent chemoradiation. These results support the re-evaluation of the role of surgery in multimodality therapy for N1 SCLC in a clinical trial setting.

    View details for DOI 10.1016/j.athoracsur.2017.01.043

    View details for PubMedID 28385378

  • Long-term Survival After Surgery Compared With Concurrent Chemoradiation for Node-negative Small Cell Lung Cancer. Annals of surgery Yang, C. J., Chan, D. Y., Shah, S. A., Yerokun, B. A., Wang, X. F., D'Amico, T. A., Berry, M. F., Harpole, D. H. 2017

    Abstract

    To determine whether surgery with adjuvant chemotherapy offers a survival advantage over concurrent chemoradiation for patients with cT1-2N0M0 small cell lung cancer (SCLC).Although surgery with adjuvant chemotherapy is the recommended treatment for patients with cT1-2N0M0 SCLC per international guidelines, there have been no prospective or retrospective studies evaluating the impact of surgery versus optimal medical management for cT1-2N0M0 SCLC.Outcomes of patients with cT1-2N0M0 SCLC who underwent surgery with adjuvant chemotherapy or concurrent chemoradiation in the National Cancer Data Base (2003-2011) were evaluated using Cox proportional hazards analyses and propensity-score-matched analyses.During the study period, 681 (30%) patients underwent surgery with adjuvant chemotherapy and 1620 (70%) underwent concurrent chemoradiation. After propensity-score matching, all 14 covariates were well balanced between the surgery (n = 501) and concurrent chemoradiation (n = 501) groups. Surgery was associated with a higher overall survival (OS) than concurrent chemoradiation (5-year OS 47.6% vs 29.8%, P < 0.01). To minimize selection bias due to comorbidities, we limited the propensity-matched analysis to 492 patients with no comorbidities; surgery remained associated with a higher OS than concurrent chemoradiation (5-year OS 49.2% vs 32.5%, P < 0.01).In a national analysis, surgery with adjuvant chemotherapy was used in the minority of patients for early stage SCLC. Surgery with adjuvant chemotherapy for node-negative SCLC was associated with improved long-term survival when compared to concurrent chemoradiation. These results suggest a significant underuse of surgery among patients with early stage SCLC and support an increased role of surgery in multimodality therapy for cT1-2N0M0 SCLC.

    View details for DOI 10.1097/SLA.0000000000002287

    View details for PubMedID 28475559

  • Socioeconomic Status, Not Race, Is Associated With Reduced Survival in Esophagectomy Patients. Annals of thoracic surgery Erhunmwunsee, L., Gulack, B. C., Rushing, C., Niedzwiecki, D., Berry, M. F., Hartwig, M. G. 2017

    Abstract

    Black patients with esophageal cancer have worse survival than white patients. This study examines this racial disparity in conjunction with socioeconomic status (SES) and explores whether race-based outcome differences exist using a national database.The associations between race and SES with overall survival of patients treated with esophagectomy for stages I to III esophageal cancer between 2003 and 2011 in the National Cancer Data Base were investigated using the Kaplan-Meier method and proportional hazards analyses. Median income by zip code and proportion of the zip code residents without a high school diploma were grouped into income and education quartiles, respectively and used as surrogates for SES. The association between race and overall survival stratified by SES is explored.Of 11,599 esophagectomy patients who met study criteria, 3,503 (30.2%) were in the highest income quartile, 2,847 (24.5%) were in the highest education quartile, and 610 patients (5%) were black. Before adjustment for SES, black patients had worse overall survival than white patients (median survival 23.0 versus 34.7 months, log rank p < 0.001), and overall, survival times improved with increasing income and education (p < 0.001 for both). After adjustment for putative prognostic factors, SES was associated with overall survival, whereas race was not.Prior studies have suggested that survival of esophageal cancer patients after esophagectomy is associated with race. Our study suggests that race is not significantly related to overall survival when adjusted for other prognostic variables. Socioeconomic status, however, remains significantly related to overall survival in our model.

    View details for DOI 10.1016/j.athoracsur.2017.01.049

    View details for PubMedID 28410639

  • Induction chemotherapy for T3N0M0 non-small-cell lung cancer increases the rate of complete resection but does not confer improved survival. European journal of cardio-thoracic surgery Anderson, K. L., Mulvihill, M. S., Yerokun, B. A., Speicher, P. J., D'Amico, T. A., Tong, B. C., Berry, M. F., Hartwig, M. G. 2017

    Abstract

    The objective of this study was to evaluate outcomes of induction therapy prior to an operation in patients with cT3 non-small-cell lung cancer (NSCLC).Patients diagnosed with cT3N0M0 NSCLC from 2006 to 2011 in the National Cancer Database who were treated with lobectomy or pneumonectomy were stratified by treatment strategy: an operation first versus induction chemotherapy. Propensity scores were developed and matched cohorts were generated. Short-term outcomes included margin status, 30- and 90-day mortality rates, readmission and length of stay. Survival analyses using Kaplan-Meier methods were performed on both the unadjusted and propensity matched cohorts.A total of 3791 cT3N0M0 patients were identified for inclusion, of which 580 (15%) were treated with induction chemotherapy. Prior to adjustment, patients treated with induction chemotherapy were younger, had a higher comorbidity burden and were more likely to have private insurance (all P  < 0.001). Following matching, patients receiving induction chemotherapy were more likely to subsequently undergo an open procedure (87.3 vs 77.8%, P  = 0.005). These patients were more likely to obtain R0 resection (93.1% vs 90.0%, P  = 0.04) and were thereby less likely to have positive margins at the time of resection (6.9% vs 10.0%, P  = 0.03). Patients who received induction therapy had higher rates of 90-day mortality (6.6% vs 3.4%) but there was no difference in long-term survival between the groups.Despite yielding increased rates of R0 resection, induction chemotherapy for cT3N0M0 NSCLC is not associated with improved survival and should not be considered routinely. Further studies are warranted to elucidate cohorts that may benefit from induction therapy.

    View details for DOI 10.1093/ejcts/ezx091

    View details for PubMedID 28402406

  • A national analysis of wedge resection versus stereotactic body radiation therapy for stage IA non-small cell lung cancer. journal of thoracic and cardiovascular surgery Yerokun, B. A., Yang, C. J., Gulack, B. C., Li, X., Mulvihill, M. S., Gu, L., Wang, X., Harpole, D. H., D'Amico, T. A., Berry, M. F., Hartwig, M. G. 2017

    Abstract

    Lobectomy is considered optimal therapy for early-stage non-small cell lung cancer, but sublobar wedge resection and stereotactic body radiation therapy are alternative treatments. This study compared outcomes between wedge resection and stereotactic body radiotherapy.Overall survival of patients with cT1N0 and tumors ≤2 cm who underwent stereotactic body radiotherapy or wedge resection in the National Cancer Data Base from 2008 to 2011 was assessed via a Kaplan-Meier and propensity score-matched analysis. A center-level sensitivity analysis that used observed/expected mortality ratios was conducted to identify an association between center use of stereotactic body radiotherapy and mortality.Of the 6295 patients included, 1778 (28.2%) underwent stereotactic body radiotherapy, and 4517 (71.8%) underwent wedge resection. Stereotactic body radiotherapy was associated with significantly reduced 5-year survival compared with wedge resection in both unmatched analysis (30.9% vs 55.2%, P < .001) and after adjustment for covariates (31.0% vs 49.9%, P < .001). Stereotactic body radiotherapy also was associated with worse overall survival than wedge resection after 2 subgroup analyses of propensity-matched patients (P < .05 for both). Centers that used stereotactic body radiotherapy more often as opposed to surgery for patients with cT1N0 patients with tumors <2 cm were more likely to have an observed/expected mortality ratio > 1 for 3-year mortality (P = .034).In this national analysis, wedge resection was associated with better survival for stage IA non-small cell lung cancer than stereotactic body radiotherapy.

    View details for DOI 10.1016/j.jtcvs.2017.02.065

    View details for PubMedID 28461054

  • Traveling to a High-volume Center is Associated With Improved Survival for Patients With Esophageal Cancer. Annals of surgery Speicher, P. J., Englum, B. R., Ganapathi, A. M., Wang, X., Hartwig, M. G., D'Amico, T. A., Berry, M. F. 2017; 265 (4): 743-749

    Abstract

    An association between volume and outcomes has been observed for esophagectomy, though little is known about why or how patients choose low- or high-volume centers. The purpose of this study was to evaluate how travel burden and hospital volume influence treatment and outcomes of patients with locally advanced esophageal cancer.Predictors of receiving esophagectomy for patients with T1-3N1M0 mid or distal esophageal cancer in the National Cancer Data Base from 2006 to 2011 were identified using multivariable logistic regression. Survival was compared using propensity score-matched groups: patients in the bottom quartile of travel distance who underwent treatment at low-volume facilities (Local) and patients in the top quartile of travel distance who underwent treatment at high-volume facilities (Travel).Of 4979 patients who met inclusion criteria, we identified 867 Local patients who traveled 2.7 [interquartile range (IQR): 1.6-4 miles] miles to centers that treated 2.6 (IQR: 1.9-3.3) esophageal cancers per year, and 317 Travel patients who traveled 107.1 (IQR: 65-247) miles to centers treating 31.9 (IQR: 30.9-38.5) cases. Travel patients were more likely to undergo esophagectomy (67.8% vs 42.9%, P < 0.001) and had significantly better 5-year survival (39.8% vs 20.6%, P < 0.001) than Local patients.Patients who travel longer distances to high-volume centers have significantly different treatment and better outcomes than patients who stay close to home at low-volume centers. Strategies that support patient travel for treatment at high-volume centers may improve esophageal cancer outcomes.

    View details for DOI 10.1097/SLA.0000000000001702

    View details for PubMedID 28266965

    View details for PubMedCentralID PMC5143210

  • The EZ-Blocker (R) in Patients With Short Tracheas JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Cohn, S., Brodsky, J. B., Berry, M. F. 2017; 31 (2): 631-632
  • Bleeding risk associated with eptifibatide (Integrilin) bridging in thoracic surgery patients JOURNAL OF THROMBOSIS AND THROMBOLYSIS Waldron, N. H., Dallas, T., Erhunmwunsee, L., Wang, T. Y., Berry, M. F., Welsby, I. J. 2017; 43 (2): 194-202

    Abstract

    Antiplatelet use for treatment of coronary artery disease (CAD) is common amongst thoracic surgery patients. Perioperative management of antiplatelet agents requires balancing the opposing risks of myocardial ischemia and excessive bleeding. Perioperative bridging with short-acting intravenous antiplatelet agents has shown promise in preventing myocardial ischemia, but may increase bleeding. We sought to determine whether perioperative bridging with eptifibatide increased bleeding associated with thoracic surgery. After Institutional Review Board approval, we identified thoracic surgery patients receiving eptifibatide at our institution (n = 30). These patients were matched 1:2 with control patients with CAD who did not receive eptifibatide from an institutional database of general thoracic surgery patients. The primary endpoint for our study was the number of units of blood transfused perioperatively. There were no differences in our primary endpoint, number of units of blood products transfused. There were also no differences noted between groups in intraoperative blood loss, chest tube duration, or postoperative length of stay (LOS). While there were no difference noted in overall complications, including our outcome of perioperative MI or death, composite cardiovascular events were more common in the eptifibatide group. In our retrospective exploratory analysis, eptifibatide bridging in patients with high-risk or recent PCI was not associated with an increased need for perioperative transfusion, bleeding, or increased LOS. In addition, we found a similar rate of perioperative mortality or myocardial infarction in both groups, though the ability of eptifibatide to protect against perioperative myocardial ischemia is unclear given different baseline CAD characteristics.

    View details for DOI 10.1007/s11239-016-1441-5

    View details for Web of Science ID 000394997800008

  • The Role of Extent of Surgical Resection and Lymph Node Assessment for Clinical Stage I Pulmonary Lepidic Adenocarcinoma: An Analysis of 1991 Patients. Journal of thoracic oncology Cox, M. L., Yang, C. J., Speicher, P. J., Anderson, K. L., Fitch, Z. W., Gu, L., Davis, R. P., Wang, X., D'Amico, T. A., Hartwig, M. G., Harpole, D. H., Berry, M. F. 2017

    Abstract

    This study examined the association of extent of lung resection, pathologic nodal evaluation, and survival for patients with clinical stage I (cT1-2N0M0) adenocarcinoma with lepidic histologic features in the National Cancer Data Base.The association between extent of surgical resection and long-term survival for patients in the National Cancer Data Base with clinical stage I lepidic adenocarcinoma who underwent lobectomy or sublobar resection was evaluated using Kaplan-Meier and Cox proportional hazards regression analyses.Of the 1991 patients with cT1-2N0M0 lepidic adenocarcinoma who met the study criteria, 1544 underwent lobectomy and 447 underwent sublobar resection. Patients treated with sublobar resection were older, more likely to be female, and had higher Charlson/Deyo comorbidity scores, but they had smaller tumors and lower T status. Of the patients treated with lobectomy, 6% (n = 92) were upstaged because of positive nodal disease, with a median of seven lymph nodes sampled (interquartile range 4-10). In an analysis of the entire cohort, lobectomy was associated with a significant survival advantage over sublobar resection in univariate analysis (median survival 9.2 versus 7.5 years, p = 0.022, 5-year survival 70.5% versus 67.8%) and after multivariable adjustment (hazard ratio = 0.81, 95% confidence interval: 0.68-0.95, p = 0.011). However, lobectomy was no longer independently associated with improved survival when compared with sublobar resection (hazard ratio = 0.99, 95% confidence interval: 0.77-1.27, p = 0.905) in a multivariable analysis of a subset of patients in which only those patients who had undergone a sublobar resection including lymph node sampling were compared with patients treated with lobectomy.Surgeons treating patients with stage I lung adenocarcinoma with lepidic features should cautiously utilize sublobar resection rather than lobectomy, and they must always perform adequate pathologic lymph node evaluation.

    View details for DOI 10.1016/j.jtho.2017.01.003

    View details for PubMedID 28082103

    View details for PubMedCentralID PMC5367982

  • Reply to T.-H. Wang et al. Journal of clinical oncology Yang, C. J., Chan, D. Y., Wang, X., D'Amico, T. A., Harpole, D. H., Berry, M. F. 2017; 35 (1): 118-120

    View details for PubMedID 28034078

  • Evidence for resection of sarcoma pulmonary metastases: More, but better? The Journal of thoracic and cardiovascular surgery Berry, M. F. 2017; 154 (1): 317–18

    View details for PubMedID 28511805

  • Adjuvant Chemotherapy Does Not Confer Superior Survival in Patients With Atypical Carcinoid Tumors. The Annals of thoracic surgery Anderson, K. L., Mulvihill, M. S., Speicher, P. J., Yerokun, B. A., Gulack, B. C., Nussbaum, D. P., Harpole, D. H., D'Amico, T. A., Berry, M. F., Hartwig, M. G. 2017; 104 (4): 1221–30

    Abstract

    Although the use of adjuvant chemotherapy in patients with pathologically node-positive (pN+) atypical carcinoid tumor of the lung is an accepted practice, controversy exists about its use in pathologically node-negative (pN0) patients. Our aim was to determine whether a survival advantage exists in patients receiving chemotherapy postoperatively for pN0 or pN+ atypical carcinoid tumors of the lung.Adult patients treated with lobectomy or pneumonectomy for pulmonary atypical carcinoid tumor were identified using the National Cancer Data Base, 2006 to 2011. Propensity scoring (4:1 nearest neighbor algorithm) and survival analysis were used to examine the association between adjuvant chemotherapy and pN+ versus pN0 atypical carcinoid tumors.Of the total 581 patients identified with a diagnosis of atypical carcinoid of the lung, 363 (62.5%) were found to be node negative at the time of operation and 218 (37.5%) had node-positive disease. Adjuvant chemotherapy was used in 15 patients (4.1%) with pN0 disease and 89 patients (40.8%) with pN+ disease. Unadjusted survival, at 12 and 60 months, was similar between pN+ patients who were treated with adjuvant chemotherapy versus patients who received operation alone (adjuvant chemotherapy: 98.9% at 12 months and 47.9% at 60 months versus operation alone: 98.4% and 12 months and 67.1% at 60 months, p = 0.46) and for propensity-matched pN0 (adjuvant chemotherapy: 86.7% at 12 months and 73.3% at 60 months versus operation alone: 87.9% at 12 months and 72.3% at 60 months, p = 0.54).In a national-level analysis, the use of adjuvant chemotherapy postoperatively in patients with pN+ and pN0 disease conferred no survival advantage; further study is needed to determine proper chemotherapy use for these patients.

    View details for PubMedID 28760471

    View details for PubMedCentralID PMC5610099

  • Video-assisted thoracoscopic diaphragm plication using a running suture technique is durable and effective. journal of thoracic and cardiovascular surgery Demos, D. S., Berry, M. F., Backhus, L. M., Shrager, J. B. 2016

    Abstract

    Surgeons have hesitated to adopt minimally invasive diaphragm plication techniques because of technical limitations rendering the procedure cumbersome or leading to early failure or reduced efficacy. We sought to demonstrate efficacy and durability of our thoracoscopic plication technique using a single running suture.We retrospectively reviewed patients who underwent our technique for diaphragm plication since 2008. We used a single, buttressed, double-layered, to-and-fro running suture with additional plicating horizontal mattress sutures as needed.Eighteen patients underwent thoracoscopic plication from 2008 to 2015. There were no operative mortalities and 2 unrelated late deaths. Median hospital stay was 3 days (range, 1-12). Atrial fibrillation occurred in 1 patient (5.5%), pneumonia occurred in 2 patients (11%), reintubation occurred in 1 patient (5.5%), and ileus occurred in 1 patient (5.5%). Of 14 patients with complete follow-up, median follow-up was 29.4 months (range, 3.4-84.7). Significant increases between preoperative and postoperative pulmonary function tests (% predicted values) were found for mean forced expiratory volume in 1 second (73.5% ± 3.5% to 88.8% ± 4.5%, P = .002) and mean forced vital capacity (70.6% ± 3.5% to 82.3% ± 3.5%, P = .002). Preoperative mean Baseline Dyspnea Index was 8.1 ± 0.7. Mean Transitional Dyspnea Index 6 months postoperatively was 7.1 ± 0.6 (moderate to major improvement). Transitional Dyspnea Index at last contact (median 29.4 months postoperatively) was 7.2 ± 0.6 (P = .38). Compared with previously published results, this is at least equivalent.Thoracoscopic diaphragm plication with a running suture is safe and achieves excellent early and long-term improvements. This addresses technical challenges of tying multiple interrupted sutures by video-assisted thoracoscopic surgery without any apparent compromise to efficacy or durability.

    View details for DOI 10.1016/j.jtcvs.2016.11.062

    View details for PubMedID 28087113

  • A Risk Score to Assist Selecting Lobectomy Versus Sublobar Resection for Early Stage Non-Small Cell Lung Cancer ANNALS OF THORACIC SURGERY Gulack, B. C., Yang, C. J., Speicher, P. J., Yerokun, B. A., Tong, B. C., Onaitis, M. W., D'Amico, T. A., Harpole, D. H., Hartwig, M. G., Berry, M. F. 2016; 102 (6): 1814-1820

    Abstract

    The long-term survival benefit of lobectomy over sublobar resection for early-stage non-small cell lung cancer must be weighed against a potentially increased risk of perioperative mortality. The objective of the current study was to create a risk score to identify patients with favorable short-term outcomes following lobectomy.The 2005-2012 American College of Surgeons National Surgical Quality Improvement Program database was queried for patients undergoing a lobectomy or sublobar resection (either segmentectomy or wedge resection) for lung cancer. A multivariable logistic regression model was utilized to determine factors associated with 30-day mortality among the lobectomy group and to develop an associated risk score to predict perioperative mortality.Of the 5,749 patients who met study criteria, 4,424 (77%) underwent lobectomy, 1,098 (19%) underwent wedge resection, and 227 (4%) underwent segmentectomy. Age, chronic obstructive pulmonary disease, previous cerebrovascular event, functional status, recent smoking status, and surgical approach (minimally invasive versus open) were utilized to develop the risk score. Patients with a risk score of 5 or lower had no significant difference in perioperative mortality by surgical procedure. Patients with a risk score greater than 5 had significantly higher perioperative mortality after lobectomy (4.9%) as compared to segmentectomy (3.6%) or wedge resection (0.8%, p < 0.01).In this study, we have developed a risk model that predicts relative operative mortality from a sublobar resection as compared to a lobectomy. Among patients with a risk score of 5 or less, lobectomy confers no additional perioperative risk over sublobar resection.

    View details for DOI 10.1016/j.athoracsur.2016.06.032

    View details for Web of Science ID 000389548100048

    View details for PubMedID 27592602

    View details for PubMedCentralID PMC5140083

  • FROZEN SECTION OF N2 NODES IS INVALUABLE WHENEVER UNEXPECTED SUSPICIOUS OPERATIVE FINDINGS ARE ENCOUNTERED JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yang, C., D'Amico, T. A., Berry, M. F. 2016; 152 (6): 1643–44

    View details for PubMedID 27842692

  • Reply to D.A. Palma. Journal of clinical oncology Yang, C. J., Chan, D. Y., D'Amico, T. A., Berry, M. F., Harpole, D. H. 2016: JCO2016702787-?

    View details for PubMedID 27870575

  • Bleeding risk associated with eptifibatide (Integrilin) bridging in thoracic surgery patients. Journal of thrombosis and thrombolysis Waldron, N. H., Dallas, T., Erhunmwunsee, L., Wang, T. Y., Berry, M. F., Welsby, I. J. 2016: -?

    Abstract

    Antiplatelet use for treatment of coronary artery disease (CAD) is common amongst thoracic surgery patients. Perioperative management of antiplatelet agents requires balancing the opposing risks of myocardial ischemia and excessive bleeding. Perioperative bridging with short-acting intravenous antiplatelet agents has shown promise in preventing myocardial ischemia, but may increase bleeding. We sought to determine whether perioperative bridging with eptifibatide increased bleeding associated with thoracic surgery. After Institutional Review Board approval, we identified thoracic surgery patients receiving eptifibatide at our institution (n = 30). These patients were matched 1:2 with control patients with CAD who did not receive eptifibatide from an institutional database of general thoracic surgery patients. The primary endpoint for our study was the number of units of blood transfused perioperatively. There were no differences in our primary endpoint, number of units of blood products transfused. There were also no differences noted between groups in intraoperative blood loss, chest tube duration, or postoperative length of stay (LOS). While there were no difference noted in overall complications, including our outcome of perioperative MI or death, composite cardiovascular events were more common in the eptifibatide group. In our retrospective exploratory analysis, eptifibatide bridging in patients with high-risk or recent PCI was not associated with an increased need for perioperative transfusion, bleeding, or increased LOS. In addition, we found a similar rate of perioperative mortality or myocardial infarction in both groups, though the ability of eptifibatide to protect against perioperative myocardial ischemia is unclear given different baseline CAD characteristics.

    View details for PubMedID 27798792

  • Invited Commentary. Annals of thoracic surgery Berry, M. F. 2016; 102 (4): 1130-1131

    View details for DOI 10.1016/j.athoracsur.2016.05.076

    View details for PubMedID 27645942

  • Outcomes of Major Lung Resection After Induction Therapy for Non-Small Cell Lung Cancer in Elderly Patients. Annals of thoracic surgery Yang, C. J., Mayne, N. R., Wang, H., Meyerhoff, R. R., Hirji, S., Tong, B. C., Hartwig, M., Harpole, D., D'Amico, T. A., Berry, M. 2016; 102 (3): 962-970

    Abstract

    This study analyzes the impact of age on perioperative outcomes and long-term survival of patients undergoing surgery after induction chemotherapy for non-small cell lung cancer.Short- and long-term outcomes of patients with non-small cell lung cancer who were at least 70 years and received induction chemotherapy followed by major lung resection (lobectomy or pneumonectomy) from 1996 to 2012 were assessed using multivariable logistic regression, Kaplan-Meier, and Cox proportional hazard analysis. The outcomes of these elderly patients were compared with those of patients younger than 70 years who underwent the same treatment from 1996 to 2012.Of the 317 patients who met the study criteria, 53 patients were at least 70 years. The median age was 74 years (range, 70 to 82 years) in the elderly group, and induction chemoradiation was used in 24 (45%) patients. Thirty-day mortality was similar between the younger (n = 12) and elderly (n = 3) patients (5% versus 6%; p = 0.52). There were no significant differences in the incidence of postoperative complications between younger and elderly patients (49% versus 57%; p = 0.30). Patients younger than 70 years had a median overall survival (30 months; 95% confidence interval [CI], 24 to 43) and a 5-year survival (39%; 95% CI, 33 to 45) that was not significantly different from patients at least 70 years (median overall survival, 30 months; 95% CI, 18 to 68; and 5-year overall survival, 36%; 95% CI, 21 to 51). However, there was a trend toward worse survival in the elderly group after multivariable adjustment (hazard ratio, 1.43; 95% CI, 0.97 to 2.12; p = 0.071).Major lung resection after induction chemotherapy can be performed with acceptable short- and long-term results in appropriately selected patients at least 70 years, with outcomes that are comparable to those of younger patients.

    View details for DOI 10.1016/j.athoracsur.2016.03.088

    View details for PubMedID 27234579

  • Impact of Age on Long-Term Outcomes of Surgery for Malignant Pleural Mesothelioma. Clinical lung cancer Yang, C. J., Yan, B. W., Meyerhoff, R. R., Saud, S. M., Gulack, B. C., Speicher, P. J., Hartwig, M. G., D'Amico, T. A., Harpole, D. H., Berry, M. F. 2016; 17 (5): 419-426

    Abstract

    Although malignant pleural mesothelioma (MPM) is generally a disease associated with more advanced age, the association of age, treatment, and outcomes has not been well-characterized. We evaluated the impact of age on outcomes in patients with MPM to provide data for use in the treatment selection process for elderly patients with potentially resectable disease.Overall survival (OS) of patients younger than 70 and 70 years or older with Stage I to III MPM who underwent cancer-directed surgery or nonoperative management in the Surveillance, Epidemiology, and End Results database (2004-2010) was evaluated using multivariable Cox proportional hazard models and propensity score-matched analysis.Cancer-directed surgery was used in 284 of 879 (32%) patients who met inclusion criteria, and was associated with improved OS in multivariable analysis (hazard ratio, 0.71; P = .001). Cancer-directed surgery was used much less commonly in patients 70 years and older compared with patients younger than 70 years (22% [109/497] vs. 46% [175/382]; P < .001), but patients 70 years and older had improved 1-year (59.4% vs. 37.9%) and 3-year (15.4% vs. 8.0%) OS compared with nonoperative management. The benefit of surgery in patients 70 years and older was observed even after propensity score-matched analysis was used to control for selection bias.Surgical treatment is associated with improved survival compared with nonoperative management for both patients younger than 70 years and patients aged 70 years or older.

    View details for DOI 10.1016/j.cllc.2016.03.002

    View details for PubMedID 27236386

    View details for PubMedCentralID PMC5026893

  • Induction Chemotherapy is Not Superior to a Surgery-First Strategy for Clinical N1 Non-Small Cell Lung Cancer. Annals of thoracic surgery Speicher, P. J., Fitch, Z. W., Gulack, B. C., Yang, C. J., Tong, B. C., Harpole, D. H., D'Amico, T. A., Berry, M. F., Hartwig, M. G. 2016; 102 (3): 884-894

    Abstract

    Guidelines recommend primary surgical resection for non-small cell lung cancer (NSCLC) patients with clinical N1 disease and adjuvant chemotherapy if nodal disease is confirmed after resection. We tested the hypothesis that induction chemotherapy for clinical N1 (cN1) disease improves survival.Patients treated with lobectomy or pneumonectomy for cT1-3 N1 M0 NSCLC from 2006 to 2011 in the National Cancer Data Base were stratified by treatment strategy: surgery first vs induction chemotherapy. Propensity scores were developed and matched with a 2:1 nearest neighbor algorithm. Survival analyses using Kaplan-Meier methods were performed on the unadjusted and propensity-matched cohorts.A total of 5,364 cN1 patients were identified for inclusion, of which 565 (10.5%) were treated with induction chemotherapy. Clinical nodal staging was accurate in 68.6% (n = 3,292) of patients treated with surgical resection first, whereas 16.3% (n = 780) were pN0 and 10.7% (n = 514) were pN2-3. Adjuvant chemotherapy was given to 60.9% of the surgery-first patients who were pN1-3 after resection. Before adjustment, patients treated with induction chemotherapy were younger, with lower comorbidity burden, were more likely to be treated at an academic center and to have private insurance (all p < 0.001), but were significantly more likely to have T3 tumors (28.7% vs 9.9%, p < 0.001) and to require pneumonectomy (23.5% vs 18.5%, p = 0.005). The unadjusted and propensity-matched analyses found no differences in short-term outcomes or survival between groups.Induction chemotherapy for cN1 NSCLC is not associated with improved survival. This finding supports the currently recommended treatment paradigm of surgery first for cN1 NSCLC.

    View details for DOI 10.1016/j.athoracsur.2016.05.065

    View details for PubMedID 27476819

  • Minimally Invasive Versus Open Esophagectomy for Esophageal Cancer: A Population-Based Analysis. Annals of thoracic surgery Yerokun, B. A., Sun, Z., Jeffrey Yang, C., Gulack, B. C., Speicher, P. J., Adam, M. A., D'Amico, T. A., Onaitis, M. W., Harpole, D. H., Berry, M. F., Hartwig, M. G. 2016; 102 (2): 416-423

    Abstract

    The objective of this study was to evaluate outcomes of minimally invasive approaches to esophagectomy using population-level data.Multivariable regression modeling was used to determine predictors associated with the use of minimally invasive approaches for patients in the National Cancer Data Base who underwent resection of middle and distal clinical T13N03M0 esophageal cancers from 2010 to 2012. Perioperative outcomes and 3-year survival were compared between propensity-matched groups of patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE) or open esophagectomy (OE). A subgroup analysis was performed to evaluate the impact of using robotic-assisted operations as part of the minimally invasive approach.Among 4,266 patients included, 1,308 (30.6%) underwent MIE. It was more likely to be used in patients treated at academic (adjusted odds ratio [OR], 10.1; 95% confidence interval [CI], 4.2-33.1) or comprehensive cancer facilities (adjusted OR, 6.4; 95% CI, 2.6-21.1). Compared with propensity-matched patients who underwent OE, patients who underwent MIE had significantly more lymph nodes examined (15 versus 13; p = 0.016) and shorter hospital lengths of stay (10 days versus 11 days; p = 0.046) but similar resection margin positivity, readmission, and 30-day mortality (all p > 0.05). Survival was similar between the matched groups at 3 years for both adenocarcinoma and squamous cell carcinoma (p > 0.05). Compared with MIE without robotic assistance, use of a robotic approach was not associated with any significant differences in perioperative outcomes (p > 0.05).The use of minimally invasive techniques to perform esophagectomy for esophageal cancer is associated with modestly improved perioperative outcomes without compromising survival.

    View details for DOI 10.1016/j.athoracsur.2016.02.078

    View details for PubMedID 27157326

  • The Role of Induction Therapy for Esophageal Cancer. Thoracic surgery clinics Berry, M. F. 2016; 26 (3): 295-304

    Abstract

    Survival of esophageal cancer generally is poor but has been improving. Induction chemoradiation is recommended before esophagectomy for locally advanced squamous cell carcinoma. Both induction chemotherapy and induction chemoradiation are found to be beneficial for locally advanced adenocarcinoma. Although a clear advantage of either strategy has not yet been demonstrated, consensus-based guidelines recommend induction chemoradiation for locally advanced adenocarcinoma.

    View details for DOI 10.1016/j.thorsurg.2016.04.006

    View details for PubMedID 27427524

  • Minimally invasive lobectomy for early stage non-small cell lung cancer-it can be done without sacrificing oncologic outcomes. Journal of thoracic disease Berry, M. F. 2016; 8 (8): E799-801

    View details for DOI 10.21037/jtd.2016.06.80

    View details for PubMedID 27620960

  • Impact of patient selection and treatment strategies on outcomes after lobectomy for biopsy-proven stage IIIA pN2 non-small cell lung cancer(aEuro) EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Yang, C. J., Adil, S. M., Anderson, K. L., Meyerhoff, R. R., Turley, R. S., Hartwig, M. G., Harpole, D. H., Tong, B. C., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2016; 49 (6): 1607-1613

    Abstract

    We evaluated the impact of patient selection and treatment strategies on long-term outcomes of patients who had lobectomy after induction therapy for stage IIIA pN2 non-small cell lung cancer (NSCLC).The impact of various patient selection, induction therapy and operative strategies on survival of patients with biopsy-proven stage IIIA pN2 NSCLC who received induction chemotherapy ± radiation followed by lobectomy from 1995 to 2012 was assessed using Cox proportional hazards analysis.From 1995 to 2012, 111 patients had lobectomy for stage IIIA pN2 NSCLC after chemotherapy ± radiation with an overall 5-year survival of 39%. The use of induction chemoradiation decreased over time; from 1996 to 2007, 46/65 (71%) patients underwent induction chemoradiation, whereas from 2007 to 2012, 36/46 (78%) patients underwent induction chemotherapy. The use of video-assisted thoracoscopic surgery (VATS) increased over the time period of the study, from 0/26 (0%) in 1996-2001, to 4/39 (10%) in 2002-07 to 33/46 (72%) in 2008-12. Compared with patients given induction chemotherapy alone, patients given additional induction radiation were more likely to have complete pathologic response (30 vs 11%, P = 0.01) but had worse 5-year survival in univariable analysis (31 vs 48%, log-rank P = 0.021). Patients who underwent pathologic mediastinal restaging following induction therapy but prior to resection had an improved overall survival compared with patients who did not undergo pathologic mediastinal restaging {5-year survival: 45.2 [95% confidence interval (CI): 33.9-55.9] vs 13.9% (95% CI: 2.5-34.7); log-rank, P = 0.004}. In multivariable analysis, the particular induction therapy strategy and the surgical approach used, as well as the extent of mediastinal disease were not important predictors of survival. However, pathologic mediastinal restaging was associated with improved survival (HR 0.39; 95% CI: 0.21-0.72; P = 0.003).For patients with stage IIIA pN2 NSCLC, the VATS approach or the addition of radiation to induction therapy can be selectively employed without compromising survival. The strategy of assessing response to induction therapy with pathologic mediastinal restaging allows one to select appropriate patients for complete resection and is associated with a 5-year overall survival of 39% in this population.

    View details for DOI 10.1093/ejcts/ezv431

    View details for Web of Science ID 000378498700012

    View details for PubMedID 26719403

    View details for PubMedCentralID PMC4867397

  • Long-term survival following open versus thoracoscopic lobectomy after preoperative chemotherapy for non-small cell lung cancer(aEuro) EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Yang, C. J., Meyerhoff, R. R., Mayne, N. R., Singhapricha, T., Toomey, C. B., Speicher, P. J., Hartwig, M. G., Tong, B. C., Onaitis, M. W., Harpole, D. H., D'Amico, T. A., Berry, M. F. 2016; 49 (6): 1615-1623

    Abstract

    Video-assisted thoracoscopic (VATS) lobectomy is increasingly accepted for the management of early-stage non-small cell lung cancer (NSCLC), but its role for locally advanced cancers has not been as well characterized. We compared outcomes of patients who received induction therapy followed by lobectomy, via VATS or thoracotomy.Perioperative complications and long-term survival of all patients with NSCLC who received induction chemotherapy (ICT) (with or without induction radiation therapy) followed by lobectomy from 1996-2012 were assessed using Kaplan-Meier and Cox proportional hazard analysis. Propensity score-matched comparisons were used to assess the potential impact of selection bias.From 1996 to 2012, 272 patients met inclusion criteria and underwent lobectomy after ICT: 69 (25%) by VATS and 203 (75%) by thoracotomy. An 'intent-to-treat' analysis was performed. Compared with thoracotomy patients, VATS patients had a higher clinical stage, were older, had greater body mass index, and were more likely to have coronary disease and chronic obstructive pulmonary disease. Induction radiation was used more commonly in thoracotomy patients [VATS 28% (n = 19) vs open 72% (n = 146), P < 0.001]. Thirty-day mortality was similar between the VATS [3% (n = 2)] and open [4% (n = 8)] groups (P = 0.69). Seven (10%) of the VATS cases were converted to thoracotomy due to difficulty in dissection from fibrotic tissue and adhesions (n = 5) or bleeding (n = 2); none of these conversions led to perioperative deaths. In univariate analysis, VATS patients had improved 3-year survival compared with thoracotomy (61% vs 43%, P = 0.010). In multivariable analysis, the VATS approach showed a trend towards improved survival, but this did not reach statistical significance (hazard ratio, 0.56; 95% confidence interval, 0.32-1.01; P = 0.053). Moreover, a propensity score-matched analysis balancing patient characteristics demonstrated that the VATS approach had similar survival to an open approach (P = 0.56).VATS lobectomy in patients treated with induction therapy for locally advanced NSCLC is feasible and effective and does not appear to compromise oncologic outcomes.

    View details for DOI 10.1093/ejcts/ezv428

    View details for Web of Science ID 000378498700014

    View details for PubMedID 26719408

    View details for PubMedCentralID PMC4867396

  • Surgery versus optimal medical management of early-stage small cell lung cancer. Yang, C., Chan, D. Y., Yerokun, B., Wang, X. F., Tong, B., D'Amico, T. A., Onaitis, M. W., Hartwig, M. G., Berry, M. F., Harpole, D. AMER SOC CLINICAL ONCOLOGY. 2016
  • Long-term outcomes after lobectomy for non small cell lung cancer when unsuspected pN2 disease is found: A National Cancer Data Base analysis JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yang, C. J., Kumar, A., Gulack, B. C., Mulvihill, M. S., Hartwig, M. G., Wang, X., D'Amico, T. A., Berry, M. F. 2016; 151 (5): 1380-1388

    Abstract

    There are few studies evaluating whether to proceed with planned resection when a patient with non-small cell lung cancer (NSCLC) unexpectedly is found to have N2 disease at the time of thoracoscopy or thoracotomy. To help guide management of this clinical scenario, we evaluated outcomes for patients who were upstaged to pN2 after lobectomy without induction therapy using the National Cancer Data Base (NCDB).Survival of NSCLC patients treated with lobectomy for clinically unsuspected mediastinal nodal disease (cT1-cT3 cN0-cN1, pN2 disease) from 1998-2006 in the NCDB was compared with "suspected" N2 disease patients (cT1-cT3 cN2) who were treated with chemotherapy with or without radiation followed by lobectomy, using matched analysis based on propensity scores.Unsuspected pN2 disease was found in 4.4% of patients (2047 out of 46,691) who underwent lobectomy as primary therapy for cT1-cT3 cN0-cN1 NSCLC. The 5-year survival was 42%, 36%, 21%, and 28% for patients who underwent adjuvant chemotherapy (n = 385), chemoradiation (n = 504), radiation (n = 300), and no adjuvant therapy (n = 858), respectively. Five-year survival of the entire unsuspected pN2 cohort was worse than survival of 2302 patients who were treated with lobectomy after induction therapy for clinical N2 disease (30% vs 40%; P < .001), although no significant difference in 5-year survival was found in a matched-analysis of 655 patients from each group (37% vs 37%; P = .95).This population-based analysis suggests that, in the setting of unsuspected pN2 NSCLC, proceeding with lobectomy does not appear to compromise outcomes if adjuvant chemotherapy with or without radiation therapy can be administered following surgery.

    View details for DOI 10.1016/j.jtcvs.2015.12.028

    View details for Web of Science ID 000374118100035

    View details for PubMedID 26874598

    View details for PubMedCentralID PMC4834248

  • in Patients With Short Tracheas. Journal of cardiothoracic and vascular anesthesia Cohn, S., Brodsky, J. B., Berry, M. F. 2016

    View details for DOI 10.1053/j.jvca.2016.04.029

    View details for PubMedID 27542904

  • Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer. Journal of clinical oncology Yang, C. J., Chan, D. Y., Speicher, P. J., Gulack, B. C., Wang, X., Hartwig, M. G., Onaitis, M. W., Tong, B. C., D'Amico, T. A., Berry, M. F., Harpole, D. H. 2016; 34 (10): 1057-1064

    Abstract

    Data on optimal adjuvant therapy after complete resection of small-cell lung cancer (SCLC) are limited, and in particular, there have been no studies evaluating the role of adjuvant chemotherapy, with or without prophylactic cranial irradiation, relative to no adjuvant therapy for stage T1-2N0M0 SCLC. This National Cancer Data Base analysis was performed to determine the potential benefits of adjuvant chemotherapy with and without prophylactic cranial irradiation in patients who undergo complete resection for early-stage small-cell lung cancer.Overall survival of patients with pathologic T1-2N0M0 SCLC who underwent complete resection in the National Cancer Data Base from 2003 to 2011, stratified by adjuvant therapy regimen, was evaluated using Kaplan-Meier and Cox proportional hazards analysis. Patients treated with induction therapy and those who died within 30 days of surgery were excluded from analysis.Of 1,574 patients who had pT1-2N0M0 SCLC during the study period, 954 patients (61%) underwent complete R0 resection with a 5-year survival of 47%. Adjuvant therapy was administered to 59% of patients (n = 566), including chemotherapy alone (n = 354), chemoradiation (n = 190, including 99 patients who underwent cranial irradiation), and radiation alone (n = 22). Compared with surgery alone, adjuvant chemotherapy with or without radiation was associated with significantly improved survival. In addition, multivariable Cox modeling demonstrated that treatment with adjuvant chemotherapy (hazard ratio [HR], 0.78; 95% CI, 0.63 to 0.95) or chemotherapy with radiation directed at the brain (HR, 0.52; 95% CI, 0.36 to 0.75) was associated with improved survival when compared with no adjuvant therapy.Patients with pT1-2N0M0 SCLC treated with surgical resection alone have worse outcomes than those who undergo resection with adjuvant chemotherapy alone or chemotherapy with cranial irradiation.

    View details for DOI 10.1200/JCO.2015.63.8171

    View details for PubMedID 26786925

  • Use and Outcomes of Minimally Invasive Lobectomy for Stage I Non-Small Cell Lung Cancer in the National Cancer Data Base ANNALS OF THORACIC SURGERY Yang, C. J., Sun, Z., Speicher, P. J., Saud, S. M., Gulack, B. C., Hartwig, M. G., Harpole, D. H., Onaitis, M. W., Tong, B. C., D'Amico, T. A., Berry, M. F. 2016; 101 (3): 1037-1042

    Abstract

    Previous studies have raised concerns that video-assisted thoracoscopic (VATS) lobectomy may compromise nodal evaluation. The advantages or limitations of robotic lobectomy have not been thoroughly evaluated.Perioperative outcomes and survival of patients who underwent open versus minimally-invasive surgery (MIS [VATS and robotic]) lobectomy and VATS versus robotic lobectomy for clinical T1-2, N0 non-small cell lung cancer from 2010 to 2012 in the National Cancer Data Base were evaluated using propensity score matching.Of 30,040 lobectomies, 7,824 were VATS and 2,025 were robotic. After propensity score matching, when compared with the open approach (n = 9,390), MIS (n = 9,390) was found to have increased 30-day readmission rates (5% versus 4%, p < 0.01), shorter median hospital length of stay (5 versus 6 days, p < 0.01), and improved 2-year survival (87% versus 86%, p = 0.04). There were no significant differences in nodal upstaging and 30-day mortality between the two groups. After propensity score matching, when compared with the robotic group (n = 1,938), VATS (n = 1,938) was not significantly different from robotics with regard to nodal upstaging, 30-day mortality, and 2-year survival.In this population-based analysis, MIS (VATS and robotic) lobectomy was used in the minority of patients for stage I non-small cell lung cancer. MIS lobectomy was associated with shorter length of hospital stay and was not associated with increased perioperative mortality, compromised nodal evaluation, or reduced short-term survival when compared with the open approach. These results suggest the need for broader implementation of MIS techniques.

    View details for DOI 10.1016/j.athoracsur.2015.11.018

    View details for Web of Science ID 000370339700038

    View details for PubMedID 26822346

    View details for PubMedCentralID PMC4763985

  • Large clinical databases for the study of lung cancer: Making up for the failure of randomized trials JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yang, C., Hartwig, M. G., D'Amico, T. A., Berry, M. F. 2016; 151 (3): 626–28

    View details for PubMedID 26432720

    View details for PubMedCentralID PMC5497840

  • Impact of Positive Margins on Survival in Patients Undergoing Esophagogastrectomy for Esophageal Cancer ANNALS OF THORACIC SURGERY Javidfar, J., Speicher, P. J., Hartwig, M. G., D'Amico, T. A., Berry, M. F. 2016; 101 (3): 1060-1067

    Abstract

    Multimodality treatment that includes esophagogastrectomy may represent the best option for curing accurately staged patients with esophageal cancer. We analyzed the impact of incomplete resection on outcomes after esophagogastrectomy for esophageal cancer.The incidence of positive margins for patients who underwent esophagogastrectomy without induction therapy for pathologic T1-3N0-1M0 esophageal cancer of the mid and lower esophagus from 2003 to 2006 in the National Cancer Database was analyzed with multivariate logistic regression. The impact of positive margins on survival was assessed using Kaplan-Meier and Cox proportional hazards analysis.Positive margins occurred in 342 of 3,125 patients (10.9%) who met study criteria. Increasing clinical T status was an independent predictor of positive margins in multivariate analysis, but the chance of positive margins decreased with larger facility case volumes. The presence of clinical nodal disease was not predictive of an incomplete resection. The 5-year survival of patients with positive margins (13.8%, 95% confidence interval [CI]: 10.5% to 18.1%) was significantly worse than that for patients with negative margins (46.3%, 95% CI: 44.4% to 48.3%, p < 0.001). Both microscopic residual disease (hazard ratio 1.37, 95% CI: 1.16 to 1.60, p < 0.001) and gross residual disease (hazard ratio 1.98, 95% CI: 1.62 to 2.42, p < 0.001) predicted worse survival in multivariate analysis of the entire cohort. Receiving adjuvant chemoradiation therapy slightly improved 5-year survival of patients with positive margins (16.9%, 95% CI: 11.3% to 23.6%, versus 13.5%, 95% CI: 9% to 20.3%, p < 0.001).Positive margins are associated with poor survival, and adjuvant therapy only marginally improved prognosis. Future studies are needed to better evaluate whether induction therapy can lower the incidence of positive margins.

    View details for DOI 10.1016/j.athoracsur.2015.09.005

    View details for Web of Science ID 000370339700041

    View details for PubMedID 26576752

  • Sublobar Resection for Clinical Stage IA Non-small-cell Lung Cancer in the United States CLINICAL LUNG CANCER Speicher, P. J., Gu, L., Gulack, B. C., Wang, X., D'Amico, T. A., Hartwig, M. G., Berry, M. F. 2016; 17 (1): 47-55

    Abstract

    This study evaluated the use of lobectomy and sublobar resection for clinical stage IA non-small-cell lung cancer (NSCLC) in the National Cancer Data Base (NCDB).The NCDB from 2003 to 2011 was analyzed to determine factors associated with the use of a sublobar resection versus a lobectomy for the treatment of clinical stage IA NSCLC. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazard modeling.Among 39,403 patients included for analysis, 29,736 (75.5%) received a lobectomy and 9667 (24.5%) received a sublobar resection: 84.7% wedge resection (n = 8192) and 15.3% segmental resection (n = 1475). Lymph node evaluation was not performed in 2788 (28.8%) of sublobar resection patients, and 7298 (75.5%) of sublobar resections were for tumors ≤ 2 cm. After multivariable logistic regression, older age, higher Charlson-Deyo comorbidity scores, smaller tumor size, and treatment at lower-volume institutions were associated with sublobar resection (all P < .001). Overall, lobectomy was associated with significantly improved 5-year survival compared to sublobar resection (66.2% vs. 51.2%; P < .001, adjusted hazard ratio 0.66; P < .001). However among sublobar resection patients, nodal sampling was associated with significantly better 5-year survival (58.2% vs. 46.4%; P < .001).Despite adjustment for patient and tumor related characteristics, a sublobar resection is associated with significantly reduced long-term survival compared to a formal surgical lobectomy among patients with NSCLC, even for stage 1A tumors. For patients who cannot tolerate lobectomy and who are treated with sublobar resection, lymph node evaluation is essential to help guide further treatment.

    View details for DOI 10.1016/j.cllc.2015.07.005

    View details for Web of Science ID 000367538900007

    View details for PubMedCentralID PMC5040950

  • Sublobar Resection for Clinical Stage IA Non-small-cell Lung Cancer in the United States. Clinical lung cancer Speicher, P. J., Gu, L., Gulack, B. C., Wang, X., D'Amico, T. A., Hartwig, M. G., Berry, M. F. 2016; 17 (1): 47-55

    Abstract

    This study evaluated the use of lobectomy and sublobar resection for clinical stage IA non-small-cell lung cancer (NSCLC) in the National Cancer Data Base (NCDB).The NCDB from 2003 to 2011 was analyzed to determine factors associated with the use of a sublobar resection versus a lobectomy for the treatment of clinical stage IA NSCLC. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazard modeling.Among 39,403 patients included for analysis, 29,736 (75.5%) received a lobectomy and 9667 (24.5%) received a sublobar resection: 84.7% wedge resection (n = 8192) and 15.3% segmental resection (n = 1475). Lymph node evaluation was not performed in 2788 (28.8%) of sublobar resection patients, and 7298 (75.5%) of sublobar resections were for tumors ≤ 2 cm. After multivariable logistic regression, older age, higher Charlson-Deyo comorbidity scores, smaller tumor size, and treatment at lower-volume institutions were associated with sublobar resection (all P < .001). Overall, lobectomy was associated with significantly improved 5-year survival compared to sublobar resection (66.2% vs. 51.2%; P < .001, adjusted hazard ratio 0.66; P < .001). However among sublobar resection patients, nodal sampling was associated with significantly better 5-year survival (58.2% vs. 46.4%; P < .001).Despite adjustment for patient and tumor related characteristics, a sublobar resection is associated with significantly reduced long-term survival compared to a formal surgical lobectomy among patients with NSCLC, even for stage 1A tumors. For patients who cannot tolerate lobectomy and who are treated with sublobar resection, lymph node evaluation is essential to help guide further treatment.

    View details for DOI 10.1016/j.cllc.2015.07.005

    View details for PubMedID 26602547

    View details for PubMedCentralID PMC5040950

  • Risk calculators are useful but.... The Journal of thoracic and cardiovascular surgery Wang, X. n., Berry, M. F. 2016; 151 (3): 706–7

    View details for PubMedID 26896356

    View details for PubMedCentralID PMC4766856

  • Esophageal Cancer: Improvements in Treatment, Staging, and Now Prognostic Indicators? Seminars in thoracic and cardiovascular surgery Berry, M. F. 2016; 28 (2): 559–60

    View details for PubMedID 28043476

  • The impact of tumor size on the association of the extent of lymph node resection and survival in clinical stage I non-small cell lung cancer LUNG CANCER Gulack, B. C., Yang, C. J., Speicher, P. J., Meza, J. M., Gu, L., Wang, X., D'Amico, T. A., Hartwig, M. G., Berry, M. F. 2015; 90 (3): 554-560

    Abstract

    Lymph node evaluation for node-negative non-small cell lung cancer (NSCLC) is associated with long-term survival but it is not clear if smaller tumors require as extensive a pathologic nodal assessment as larger tumors. This study evaluated the relationship of tumor size and optimal extent of lymph node resection using the National Cancer Data Base (NCDB).The incremental survival benefit of each additional lymph node that was evaluated for patients in the NCDB who underwent lobectomy for clinical Stage I NSCLC from 2003 to 2006 was evaluated using Cox multivariable proportional hazards regression modeling. The impact of tumor size was assessed by repeating the Cox analysis with patients stratified by tumor size ≥2 cm vs <2 cm.A median of 7 [interquartile range: 4,11] lymph nodes were examined in 13,827 patients who met study criteria. Following adjustment, the evaluation of each additional lymph node demonstrated a significant survival benefit through 11 lymph nodes. After grouping patients by tumor size, patients with tumors <2 cm demonstrated a significant survival benefit for the incremental resection of each additional lymph node through 4 lymph nodes while patients with tumors ≥2 cm had a significant survival benefit through 14 lymph nodes.Pathologic lymph node evaluation is associated with improved survival for clinically node-negative NSCLC, but the extent of the necessary evaluation varies by tumor size. These results have implications for guidelines for lymph node assessment as well as the choice of surgery vs other ablative techniques for clinical stage I NSCLC.

    View details for DOI 10.1016/j.lungcan.2015.10.011

    View details for Web of Science ID 000366873700027

    View details for PubMedCentralID PMC4724282

  • The impact of tumor size on the association of the extent of lymph node resection and survival in clinical stage I non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) Gulack, B. C., Yang, C. J., Speicher, P. J., Meza, J. M., Gu, L., Wang, X., D'Amico, T. A., Hartwig, M. G., Berry, M. F. 2015; 90 (3): 554-60

    Abstract

    Lymph node evaluation for node-negative non-small cell lung cancer (NSCLC) is associated with long-term survival but it is not clear if smaller tumors require as extensive a pathologic nodal assessment as larger tumors. This study evaluated the relationship of tumor size and optimal extent of lymph node resection using the National Cancer Data Base (NCDB).The incremental survival benefit of each additional lymph node that was evaluated for patients in the NCDB who underwent lobectomy for clinical Stage I NSCLC from 2003 to 2006 was evaluated using Cox multivariable proportional hazards regression modeling. The impact of tumor size was assessed by repeating the Cox analysis with patients stratified by tumor size ≥2 cm vs <2 cm.A median of 7 [interquartile range: 4,11] lymph nodes were examined in 13,827 patients who met study criteria. Following adjustment, the evaluation of each additional lymph node demonstrated a significant survival benefit through 11 lymph nodes. After grouping patients by tumor size, patients with tumors <2 cm demonstrated a significant survival benefit for the incremental resection of each additional lymph node through 4 lymph nodes while patients with tumors ≥2 cm had a significant survival benefit through 14 lymph nodes.Pathologic lymph node evaluation is associated with improved survival for clinically node-negative NSCLC, but the extent of the necessary evaluation varies by tumor size. These results have implications for guidelines for lymph node assessment as well as the choice of surgery vs other ablative techniques for clinical stage I NSCLC.

    View details for DOI 10.1016/j.lungcan.2015.10.011

    View details for PubMedID 26519122

    View details for PubMedCentralID PMC4724282

  • Adding radiation to induction chemotherapy does not improve survival of patients with operable clinical N2 non-small cell lung cancer JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Yang, C. J., Gulack, B. C., Gu, L., Speicher, P. J., Wang, X., Harpole, D. H., Onaitis, M. W., D'Amico, T. A., Berry, M. F., Hartwig, M. G. 2015; 150 (6): 1484-1492

    Abstract

    Radiotherapy is commonly used in induction regimens for patients with non-small cell lung cancer with operable mediastinal nodal disease, although evidence has not shown a benefit over induction chemotherapy alone. We compared outcomes between induction chemotherapy and induction chemoradiation using the National Cancer Data Base.Induction radiation use and survival of patients who underwent lobectomy or pneumonectomy after induction chemotherapy for clinical T1-3N2M0 non-small cell lung cancer in the National Cancer Data Base from 2003 to 2006 were assessed using logistic regression, general linear regression, Kaplan-Meier, and Cox proportional hazard analysis.Of 1362 patients who met study criteria, 834 (61%) underwent induction chemoradiation and 528 (39%) underwent induction chemotherapy. Lobectomy was performed in 82% of patients (n = 1111), and pneumonectomy was performed in 18% of patients (n = 251). Pneumonectomy was performed more often after induction chemoradiation than after induction chemotherapy (20% vs 16%, P = .04). Downstaging from N2 to N0/N1 was more common with induction chemoradiation compared with induction chemotherapy (58% vs 46%, P < .01), but 5-year survival of patients receiving induction chemoradiation and patients receiving induction chemotherapy was similar in unadjusted analysis (41% vs 41%, P = .41). In multivariable analysis, the addition of radiation to induction chemotherapy also was not associated with a survival benefit (hazard ratio, 1.03; 95% confidence interval, 0.89-1.18; P = .73).Induction chemoradiation is used in the majority of patients with non-small cell lung cancer with N2 disease who undergo induction therapy before surgical resection, but it is not associated with improved survival compared with induction chemotherapy.

    View details for DOI 10.1016/j.jtcvs.2015.06.062

    View details for Web of Science ID 000365040700034

    View details for PubMedID 26259994

    View details for PubMedCentralID PMC4651719

  • Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer. Diseases of the esophagus Speicher, P. J., Wang, X., Englum, B. R., Ganapathi, A. M., Yerokun, B., Hartwig, M. G., D'Amico, T. A., Berry, M. F. 2015; 28 (8): 788-796

    Abstract

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N+ esophageal cancer, prior to esophagectomy.

    View details for DOI 10.1111/dote.12285

    View details for PubMedID 25212528

  • Troubleshooting thoracoscopic anterior mediastinal surgery: lessons learned from thoracoscopic lobectomy. Annals of cardiothoracic surgery Hirji, S. A., Balderson, S. S., Berry, M. F., D'Amico, T. A. 2015; 4 (6): 545-549

    Abstract

    Video-assisted thoracoscopic surgery (VATS) lobectomy is safe, oncologically effective, and increasingly utilized for lung cancer resection. Lessons from VATS lobectomy experience can guide the use of a VATS approach to resect mediastinal masses. Exposure and dissection when using VATS to resect anterior mediastinal masses has unique challenges. Several maneuvers acquired from experience with VATS lobectomy can reduce the technical difficulty and often prevent conversion to an open approach. In this troubleshooting guide, we offer 'tips' to both avoid and manage numerous intra-operative technical difficulties that commonly arise during VATS anterior mediastinal procedures. Avoiding an open approach may improve outcomes, although conversion for safety or complete resection can be necessary. Techniques and experiences derived from VATS lobectomy can facilitate VATS resection of mediastinal masses.

    View details for DOI 10.3978/j.issn.2225-319X.2015.07.04

    View details for PubMedID 26693151

    View details for PubMedCentralID PMC4669260

  • IMPACTS OF CEREBROVASCULAR AND NEURODEGENERATIVE DISEASES ON SURVIVAL OF LUNG CANCER PATIENTS Kravchenko, J., Berry, M. F., Arbeev, K. G., Lyerly, H., Yashin, A. I., Akushevich, I. OXFORD UNIV PRESS INC. 2015: 496
  • Dosimetric Predictors of Surgical Complications From Esophagectomy After Neoadjuvant Chemoradiation for Esophageal Cancer Shah, J. L., Johannet, P., Shaffer, J., Holcombe, C., Koong, A. C., Berry, M., Chang, D. T. ELSEVIER SCIENCE INC. 2015: E131
  • Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer DISEASES OF THE ESOPHAGUS Speicher, P. J., Wang, X., Englum, B. R., Ganapathi, A. M., Yerokun, B., Hartwig, M. G., D'Amico, T. A., Berry, M. F. 2015; 28 (8): 788-796

    Abstract

    The purpose of this study was to examine the role of induction chemoradiation in the treatment of potentially resectable locally advanced (T2-3N0 and T1-3N+) esophageal cancer utilizing a large national database. The National Cancer Data Base (NCDB) was queried for all patients undergoing esophagectomy for clinical T2-3N0 and T1-3N+ esophageal cancer of the mid- or lower esophagus. Patients were stratified by the use of induction chemoradiation therapy versus surgery-first. Trends were assessed with the Cochran-Armitage test. Predictors of receiving induction therapy were evaluated with multivariable logistic regression. A propensity-matched analysis was conducted to compare outcomes between groups, and the Kaplan-Meier method was used to estimate long-term survival. Within the NCDB, 7921 patients were identified, of which 6103 (77.0%) were treated with chemoradiation prior to esophagectomy, while the remaining 1818 (23.0%) were managed with surgery-first. Use of induction therapy increased over time, with an absolute increase of 11.8% from 2003-2011 (P < 0.001). As revealed by the propensity model, induction therapy was associated with higher rates of negative margins and shorter hospital length of stay, but no differences in unplanned readmission and 30-day mortality rates. In unadjusted survival analysis, induction therapy was associated with better long-term survival compared to a strategy of surgery-first, with 5-year survival rates of 37.2% versus 28.6%, P < 0.001. Following propensity score matching analysis, the use of induction therapy maintained a significant survival advantage over surgery-first (5-year survival: 37.9% vs. 28.7%, P < 0.001). Treatment with induction chemoradiation therapy prior to surgical resection is associated with significant improvement in long-term survival, even after adjusting for confounders with a propensity model. Induction therapy should be considered in all medically appropriate patients with resectable cT2-3N0 and cT1-3N+ esophageal cancer, prior to esophagectomy.

    View details for DOI 10.1111/dote.12285

    View details for Web of Science ID 000368332300011

  • Computed Tomography (CT) Characteristics Associated with the Proposed IASLC/ITMIG TNM Pathologic Staging System for Thymoma Padda, S. K., Terrone, D., Khuong, A., Tian, L., Neal, J. W., Riess, J. W., Berry, M., Leung, A. N., Schwartz, E. J., Shrager, J. B., Wakelee, H. A. ELSEVIER SCIENCE INC. 2015: S196
  • Pulmonary Artery Bleeding During Video-Assisted Thoracoscopic Surgery: Intraoperative Bleeding and Control. Thoracic surgery clinics Berry, M. F. 2015; 25 (3): 239-247

    Abstract

    With appropriate planning and operative technique, the risk of pulmonary artery injury and bleeding during video-assisted thoracoscopic surgery (VATS) lobectomy can be minimized. However, the risk cannot be completely eliminated; surgeons should always ensure that they are prepared to manage this situation if it occurs. Although pulmonary artery bleeding can potentially lead to intraoperative disasters, appropriate judgment, management, and control via VATS or conversion to thoracotomy can avoid any impact on either short-term or long-term patient outcomes.

    View details for DOI 10.1016/j.thorsurg.2015.04.007

    View details for PubMedID 26210920

  • Impact of Pulmonary Function Measurements on Long-Term Survival After Lobectomy for Stage I Non-Small Cell Lung Cancer ANNALS OF THORACIC SURGERY Berry, M. F., Yang, C. J., Hartwig, M. G., Tong, B. C., Harpole, D. H., D'Amico, T. A., Onaitis, M. W. 2015; 100 (1): 271-277

    Abstract

    Pulmonary function tests predict respiratory complications after lobectomy. We evaluated the impact of pulmonary function measurements on long-term survival after lobectomy for stage I non-small cell lung cancer.The relationship between percent predicted forced expiratory volume in 1 second (FEV1) and percent predicted diffusing capacity of the lung for carbon monoxide (Dlco) and overall survival for patients who underwent lobectomy without induction therapy for stage I (T1-2N0M0) non-small cell lung cancer from 1996 to 2012 was evaluated using the Kaplan-Meier approach and a multivariable Cox proportional hazard model.During the study period, 972 patients (mean Dlco 76 ± 21, mean FEV1 73 ± 21) met inclusion criteria. Perioperative mortality was 2.6% (n = 25). The 5-year survival of the entire cohort was 60.1%, with a median follow-up of 43 months. The 5-year survival for patients with percent predicted FEV1 stratified by more than 80%, 61% to 80%, 41% to 60%, and 40% or less was 70.1%, 59.3%, 52.5%, and 53.4%, respectively. The 5-year survival for patients with percent predicted Dlco stratified by more than 80%, 61% to 80%, 41% to 60%, and 40% or less was 70.2%, 63.4%, 44.2%, and 33.1%, respectively. In multivariable survival analysis, both larger tumor size (hazard ratio 1.15, p = 0.01) and lower Dlco (hazard ratio 0.986, p < 0.0001) were significant predictors of worse survival. The association of FEV1 and survival was not statistically significant (p = 0.18).Survival after lobectomy for patients with stage I non-small cell lung cancer is impacted by lower Dlco, which can be used in the risk and benefit assessment when choosing therapy.

    View details for DOI 10.1016/j.athoracsur.2015.02.076

    View details for Web of Science ID 000358796800050

    View details for PubMedCentralID PMC4492856

  • Impact of Pulmonary Function Measurements on Long-Term Survival After Lobectomy for Stage I Non-Small Cell Lung Cancer. Annals of thoracic surgery Berry, M. F., Jeffrey Yang, C., Hartwig, M. G., Tong, B. C., Harpole, D. H., D'Amico, T. A., Onaitis, M. W. 2015; 100 (1): 271-276

    Abstract

    Pulmonary function tests predict respiratory complications after lobectomy. We evaluated the impact of pulmonary function measurements on long-term survival after lobectomy for stage I non-small cell lung cancer.The relationship between percent predicted forced expiratory volume in 1 second (FEV1) and percent predicted diffusing capacity of the lung for carbon monoxide (Dlco) and overall survival for patients who underwent lobectomy without induction therapy for stage I (T1-2N0M0) non-small cell lung cancer from 1996 to 2012 was evaluated using the Kaplan-Meier approach and a multivariable Cox proportional hazard model.During the study period, 972 patients (mean Dlco 76 ± 21, mean FEV1 73 ± 21) met inclusion criteria. Perioperative mortality was 2.6% (n = 25). The 5-year survival of the entire cohort was 60.1%, with a median follow-up of 43 months. The 5-year survival for patients with percent predicted FEV1 stratified by more than 80%, 61% to 80%, 41% to 60%, and 40% or less was 70.1%, 59.3%, 52.5%, and 53.4%, respectively. The 5-year survival for patients with percent predicted Dlco stratified by more than 80%, 61% to 80%, 41% to 60%, and 40% or less was 70.2%, 63.4%, 44.2%, and 33.1%, respectively. In multivariable survival analysis, both larger tumor size (hazard ratio 1.15, p = 0.01) and lower Dlco (hazard ratio 0.986, p < 0.0001) were significant predictors of worse survival. The association of FEV1 and survival was not statistically significant (p = 0.18).Survival after lobectomy for patients with stage I non-small cell lung cancer is impacted by lower Dlco, which can be used in the risk and benefit assessment when choosing therapy.

    View details for DOI 10.1016/j.athoracsur.2015.02.076

    View details for PubMedID 25986099

    View details for PubMedCentralID PMC4492856

  • Adjuvant Chemotherapy After Lobectomy for T1-2N0 Non-Small Cell Lung Cancer: Are the Guidelines Supported? JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Speicher, P. J., Gu, L., Wang, X., Hartwig, M. G., D'Amico, T. A., Berry, M. F. 2015; 13 (6): 755-761

    Abstract

    Evidence guiding adjuvant chemotherapy (AC) use after lobectomy for stage I non-small cell lung cancer (NSCLC) is limited. This study evaluated the impact of AC use and tumor size on outcomes using a large, nationwide cancer database.The effect of AC on long-term survival among patients who underwent lobectomy for margin-negative pathologic T1-2N0M0 NSCLC in the National Cancer Data Base from 2003 to 2006 was estimated using the Kaplan-Meier method. The specific tumor size threshold at which AC began providing benefit was estimated with multivariable Cox proportional hazards modeling.Overall 3,496 of 34,360 patients (10.2%) who met inclusion criteria were treated with AC, although AC use increased over time from 2003, when only 2.7% of patients with tumors less than 4 cm and 6.2% of patients with tumors of 4 cm or larger received AC. In unadjusted survival analysis, AC was associated with a significant 5-year survival benefit for patients with tumors less than 4 cm (74.3% vs 66.9%; P<.0001) and 4 cm or greater (64.8% vs 49.8%; P<.0001). In subanalyses of patients grouped by strata of 0.5-cm increments in tumor size, AC was associated with a survival advantage for tumor sizes ranging from 3.0 to 8.5 cm.Use of AC among patients with stage I NSCLC has increased over time but remains uncommon. The results of this study support current treatment guidelines that recommend AC use after lobectomy for stage I NSCLC tumors larger than 4 cm. These results also suggest that AC use is associated with superior survival for patients with tumors ranging from 3.0 to 8.5 cm in diameter.

    View details for Web of Science ID 000356843400008

    View details for PubMedID 26085391

  • Long-Term Outcomes of Lobectomy for Non-Small Cell Lung Cancer After Definitive Radiation Treatment ANNALS OF THORACIC SURGERY Yang, C. J., Meyerhoff, R. R., Stephens, S. J., Singhapricha, T., Toomey, C. B., Anderson, K. L., Kelsey, C., Harpole, D., D'Amico, T. A., Berry, M. F. 2015; 99 (6): 1914-1920

    Abstract

    Salvage surgical resection for non-small cell lung cancer (NSCLC) patients initially treated with definitive chemotherapy and radiotherapy can be performed safely, but the long-term benefits are not well characterized.Perioperative complications and long-term survival of all patients with NSCLC who received curative-intent definitive radiotherapy, with or without chemotherapy, followed by lobectomy from 1995 to 2012 were evaluated.During the study period, 31 patients met the inclusion criteria. Clinical stage distribution was stage I in 2 (6%), stage II in 5 (16%), stage IIIA in 15 (48%), stage IIIB in 5 (16%), stage IV in 3 (10%), and unknown in 1 (3%). The reasons surgical resection was initially not considered were: patients deemed medically inoperable (5 [16%]); extent of disease was considered unresectable (21 [68%]); small cell lung cancer misdiagnosis (1 [3%]), and unknown (4 [13%]). Definitive therapy was irradiation alone in 2 (6%), concurrent chemoradiotherapy in 28 (90%), and sequential chemoradiotherapy in 1 (3%). The median radiation dose was 60 Gy. Patients were subsequently referred for resection because of obvious local relapse, medical tolerance of surgical intervention, or posttherapy imaging suggesting residual disease. The median time from radiation to lobectomy was 17.7 weeks. There were no perioperative deaths, and morbidity occurred in 15 patients (48%). None of the 3 patients with residual pathologic nodal disease survived longer than 37 months, but the 5-year survival of pN0 patients was 36%. Patients who underwent lobectomy for obvious relapse (n = 3) also did poorly, with a median overall survival of 9 months.Lobectomy after definitive radiotherapy can be done safely and is associated with reasonable long-term survival, particularly when patients do not have residual nodal disease.

    View details for DOI 10.1016/j.athoracsur.2015.01.064

    View details for Web of Science ID 000357521600019

    View details for PubMedID 25886806

    View details for PubMedCentralID PMC4458187

  • Impact of mesothelioma histologic subtype on outcomes in the Surveillance, Epidemiology, and End Results database JOURNAL OF SURGICAL RESEARCH Meyerhoff, R. R., Yang, C. J., Speicher, P. J., Gulack, B. C., Hartwig, M. G., D'Amico, T. A., Harpole, D. H., Berry, M. F. 2015; 196 (1): 23-32

    Abstract

    This study was conducted to determine how malignant pleural mesothelioma (MPM) histology was associated with the use of surgery and survival.Overall survival of patients with stage I-III epithelioid, sarcomatoid, and biphasic MPM in the Surveillance, Epidemiology, and End Results database from 2004-2010 was evaluated using multivariate Cox proportional hazards models.Of 1183 patients who met inclusion criteria, histologic subtype was epithelioid in 811 patients (69%), biphasic in 148 patients (12%), and sarcomatoid in 224 patients (19%). Median survival was 14 mo in the epithelioid group, 10 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). Cancer-directed surgery was used more often in patients with epithelioid (37%, 299/811) and biphasic (44%, 65/148) histologies as compared with patients with sarcomatoid histology (26%, 58/224; P < 0.01). Among patients who underwent surgery, median survival was 19 mo in the epithelioid group, 12 mo in the biphasic group, and 4 mo in the sarcomatoid group (P < 0.01). In multivariate analysis, surgery was associated with improved survival in the epithelioid group (hazard ratio [HR] 0.72; P < 0.01) but not in biphasic (HR 0.73; P = 0.19) or sarcomatoid (HR 0.79; P = 0.18) groups.Cancer-directed surgery is associated with significantly improved survival for MPM patients with epithelioid histology, but patients with sarcomatoid and biphasic histologies have poor prognoses that may not be favored by operative treatment. The specific histology should be identified before treatment, so that surgery can be offered to patients with epithelioid histology, as these patients are most likely to benefit.

    View details for DOI 10.1016/j.jss.2015.01.043

    View details for Web of Science ID 000354338000004

    View details for PubMedID 25791825

    View details for PubMedCentralID PMC4430361

  • Causal Effects of Time-Dependent Treatments in Older Patients with Non-Small Cell Lung Cancer PLOS ONE Akushevich, I., Arbeev, K., Kravchenko, J., Berry, M. 2015; 10 (4)

    Abstract

    Treatment selection for elderly patients with lung cancer must balance the benefits of curative/life-prolonging therapy and the risks of increased mortality due to comorbidities. Lung cancer trials generally exclude patients with comorbidities and current treatment guidelines do not specifically consider comorbidities, so treatment decisions are usually made on subjective individual-case basis.Impacts of surgery, radiation, and chemotherapy mono-treatment as well as combined chemo/radiation on one-year overall survival (compared to no-treatment) are studied for stage-specific lung cancer in 65+ y.o. patients. Methods of causal inference such as propensity score with inverse probability weighting (IPW) for time-independent and marginal structural model (MSM) for time-dependent treatments are applied to SEER-Medicare data considering the presence of comorbid diseases.122,822 patients with stage I (26.8%), II (4.5%), IIIa (11.5%), IIIb (19.9%), and IV (37.4%) lung cancer were selected. Younger age, smaller tumor size, and fewer baseline comorbidities predict better survival. Impacts of radio- and chemotherapy increased and impact of surgery decreased with more advanced cancer stages. The effects of all therapies became weaker after adjustment for selection bias, however, the changes in the effects were minor likely due to the weak selection bias or incompleteness of the list of predictors that impacted treatment choice. MSM provides more realistic estimates of treatment effects than the IPW approach for time-independent treatment.Causal inference methods provide substantive results on treatment choice and survival of older lung cancer patients with realistic expectations of potential benefits of specific treatments. Applications of these models to specific subsets of patients can aid in the development of practical guidelines that help optimize lung cancer treatment based on individual patient characteristics.

    View details for DOI 10.1371/journal.pone.0121406

    View details for Web of Science ID 000352477800055

    View details for PubMedID 25849715

    View details for PubMedCentralID PMC4388569

  • Outcomes after treatment of 17 378 patients with locally advanced (T3N0-2) non-small-cell lung cancer†. European journal of cardio-thoracic surgery Speicher, P. J., Englum, B. R., Ganapathi, A. M., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2015; 47 (4): 636-641

    Abstract

    Treatment patterns and outcomes in a population-based database were examined to identify patients likely to benefit from surgical resection of locally advanced (T3N0-2) non-small-cell lung cancer (NSCLC).Factors predicting the use of surgery for patients with T3N0-2M0 NSCLC in the Surveillance, Epidemiology and End Results (SEER) database from 1988 to 2010 were assessed using a multivariable logistic regression model. Survival was analysed using the Kaplan-Meier approach and Cox proportional hazard models. Propensity matching was used to compare outcomes after surgery and outcomes in patients who refused surgery and underwent radiation therapy (RT).Of 17 378 patients identified for study inclusion [8597 (50%) T3N0, 2304 (13%) T3N1 and 6477 (37%) T3N2], surgery was used in 7120 (41%). Only female sex and being married predicted the use of surgery, while older age, black race and N2 nodal disease predicted non-surgical management. Surgical patients overall had better long-term survival than non-surgical patients [odds ratio (OR) 0.42, 95% confidence interval (CI): 0.41-0.45, P < 0.001]. After propensity adjustment, patients who refused surgery and instead were treated with RT had significantly worse long-term survival than matched surgery patients (OR 0.65, 95% CI: 0.48-0.89, P = 0.0074). Sublobar resection and pneumonectomy predicted worse survival in patients who had surgery. Nodal disease also predicted worse survival after surgery, but surgery maintained an association with better overall survival compared with non-operative therapy among patients with both N1 (OR 0.53, P < 0.001) and N2 disease (OR 0.50, P < 0.001) in separate analyses stratified by nodal status. Older age also predicted worse survival after surgery, but patients older than 75 who were treated with surgery had significantly better long-term survival than non-operative patients (OR 0.49, 95% CI: 0.45-0.53, P < 0.001).Surgery is used in a minority of patients with locally advanced NSCLC, but is associated with better survival than non-surgical treatment, even for patients older than 75 and patients with nodal disease. Given the very poor outcomes observed with non-operative management, surgical resection should be carefully considered in all patients with locally advanced NSCLC and should not necessarily be denied because of patient age or nodal disease.

    View details for DOI 10.1093/ejcts/ezu270

    View details for PubMedID 25005840

  • Cardiovascular comorbidities and survival of lung cancer patients: Medicare data based analysis LUNG CANCER Kravchenko, J., Berry, M., Arbeev, K., Lyerly, H. K., Yashin, A., Akushevich, I. 2015; 88 (1): 85-93

    Abstract

    To evaluate the role of cardiovascular disease (CVD) comorbidity in survival of patients with non-small cell lung cancer (NSCLC).The impact of seven CVDs (at the time of NSCLC diagnosis and during subsequent follow-up) on overall survival was studied for NSCLC patients aged 65+ years using the Surveillance, Epidemiology, and End Results data linked to the U.S. Medicare data, cancer stage- and treatment-specific. Cox regression was applied to evaluate death hazard ratios of CVDs in univariable and multivariable analyses (controlling by age, TNM statuses, and 78 non-CVD comorbidities) and to investigate the effects of 128 different combinations of CVDs on patients' survival.Overall, 95,167 patients with stage I (n=29,836, 31.4%), II (n=5133, 5.4%), IIIA (n=11,884, 12.5%), IIIB (n=18,020, 18.9%), and IV (n=30,294, 31.8%) NSCLC were selected. Most CVDs increased the risk of death for stages I-IIIB patients, but did not significantly impact survival of stage IV patients. The worse survival of patients was associated with comorbid heart failure, myocardial infarction, and cardiac arrhythmias that occurred during a period of follow-up: HRs up to 1.85 (p<0.001), 1.96 (p<0.05), and 1.67 (p<0.001), respectively, varying by stage and treatment. The presence of hyperlipidemia at baseline (HR down to 0.71, p<0.05) was associated with better prognosis. Having multiple co-existing CVDs significantly increased mortality for all treatments, especially for stages I and II patients treated with surgery (HRs up to 2.89, p<0.05) and stages I-IIIB patients treated with chemotherapy (HRs up to 2.59, p<0.001) and chemotherapy and radiotherapy (HRs up to 2.20, p<0.001).CVDs impact the survival of NSCLC patients, particularly when multiple co-existing CVDs are present; the impacts vary by stage and treatment. This data should be considered in improving cancer treatment selection process for such potentially challenging patients as the elderly NSCLC patients with CVD comorbidities.

    View details for DOI 10.1016/j.lungcan.2015.01.006

    View details for Web of Science ID 000351794900014

    View details for PubMedID 25704956

    View details for PubMedCentralID PMC4375130

  • Impact of Pretreatment Imaging on Survival of Esophagectomy After Induction Therapy for Esophageal Cancer: Who Should be Given the Benefit of the Doubt? : Esophagectomy Outcomes of Patients with Suspicious Metastatic Lesions. Annals of surgical oncology Erhunmwunsee, L., Englum, B. R., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2015; 22 (3): 1020-1025

    Abstract

    We examined survival of patients who underwent esophagectomy for locally advanced esophageal cancer with foci that were suspicious for metastatic disease on initial imaging but whose disease did not progress after induction chemoradiation treatment (CRT).The impact of pre- and posttherapy staging characteristics on survival of patients who underwent esophagectomy after CRT between 2003 and 2009 was evaluated using multivariable logistic regression. Survival of patients with and without possible metastatic disease on initial imaging was compared with the log-rank test.During the study period, 71 (32 %) of 220 patients who underwent CRT followed by esophagectomy had possible distant metastatic disease on initial imaging. Patients with initial suspicion of metastases had a 5-year survival of 24.8 %. Overall survival of patients with and without possible metastatic disease on initial imaging was not significantly different (p = 0.4), but pretreatment positron emission tomography (PET) suggesting a liver lesion (hazard ratio [HR] 3.2, p = 0.003) predicted worse survival. Additional predictors of worse survival were clinical T4 status (HR 3.1, p = 0.001), post-CRT pathologic nodal status (HR 1.6, p = 0.04), and pathologically confirmed metastatic disease at or before resection (HR 3.1, p = 0.01). None of 10 patients with pathologic metastatic disease at resection lived longer than 2.5 years.Patients with possible liver metastases on pretreatment PET and patients with confirmed metastatic disease at the time of surgery do not benefit from resection. However, patients with pretreatment imaging that shows possible metastatic disease in sites other than the liver still have reasonable long-term survival after resection.

    View details for DOI 10.1245/s10434-014-4079-6

    View details for PubMedID 25234017

  • Adjuvant chemotherapy after resection of N1 non-small cell lung cancer: differential impact of new evidence on physician and patient decisions JOURNAL OF THORACIC DISEASE Coleman, B. K., Curtis, L. H., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2015; 7 (3): 243-251

    Abstract

    Adjuvant cisplatin-based chemotherapy (ACT) after resection of stages II-IIIA non-small cell lung cancer (NSCLC) modestly increased survival in several clinical trials. This study evaluated the subsequent impact of those trials on ACT use in clinical practice.Patients who underwent lobectomy or more extensive lung resection without induction chemotherapy for pathologically confirmed N1 positive NSCLC between 2000 and 2012 were reviewed. Referrals to medical oncology, oncologist recommendations for ACT, and initiation of ACT were evaluated. Because major trials supporting ACT were published in 2004 and 2005, analysis was stratified into two eras: 2000-2005 and 2006-2012.During the study period, 272 patients met inclusion criteria (110 in the 2000-2005 cohort, 162 in the 2006-2012 cohort). Referrals to medical oncology increased from 74.5% (n=82) in the 2000-2005 cohort to 90.1% (n=146) in the 2006-2012 cohort (P=0.002). Due to lack of referral or missed appointments, 35.5% (n=39) of the 2000-2005 patients and 17.9% (n=32) of the 2006-2012 patients did not have a documented conversation with an oncologist regarding ACT. The proportion of patients recommended for ACT increased from 61% (n=50) to 81.5% (n=119) between the eras (P<0.001). Of patients recommended for chemotherapy, 14% (7/50) in 2000-2005 and 13.4% (16/119) in 2006-2012 declined ACT (P=0.666).Publication of supporting evidence increased recommendations for ACT but did not change the percentage of patients who ultimately agreed to receive ACT. Additional research is needed to better understand patient decision-making in this situation.

    View details for DOI 10.3978/j.issn.2072-1439.2015.01.42

    View details for Web of Science ID 000353054200027

    View details for PubMedID 25922700

    View details for PubMedCentralID PMC4387435

  • Impact of Pretreatment Imaging on Survival of Esophagectomy After Induction Therapy for Esophageal Cancer: Who Should be Given the Benefit of the Doubt? ANNALS OF SURGICAL ONCOLOGY Erhunmwunsee, L., Englum, B. R., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2015; 22 (3): 1020-1025

    Abstract

    We examined survival of patients who underwent esophagectomy for locally advanced esophageal cancer with foci that were suspicious for metastatic disease on initial imaging but whose disease did not progress after induction chemoradiation treatment (CRT).The impact of pre- and posttherapy staging characteristics on survival of patients who underwent esophagectomy after CRT between 2003 and 2009 was evaluated using multivariable logistic regression. Survival of patients with and without possible metastatic disease on initial imaging was compared with the log-rank test.During the study period, 71 (32 %) of 220 patients who underwent CRT followed by esophagectomy had possible distant metastatic disease on initial imaging. Patients with initial suspicion of metastases had a 5-year survival of 24.8 %. Overall survival of patients with and without possible metastatic disease on initial imaging was not significantly different (p = 0.4), but pretreatment positron emission tomography (PET) suggesting a liver lesion (hazard ratio [HR] 3.2, p = 0.003) predicted worse survival. Additional predictors of worse survival were clinical T4 status (HR 3.1, p = 0.001), post-CRT pathologic nodal status (HR 1.6, p = 0.04), and pathologically confirmed metastatic disease at or before resection (HR 3.1, p = 0.01). None of 10 patients with pathologic metastatic disease at resection lived longer than 2.5 years.Patients with possible liver metastases on pretreatment PET and patients with confirmed metastatic disease at the time of surgery do not benefit from resection. However, patients with pretreatment imaging that shows possible metastatic disease in sites other than the liver still have reasonable long-term survival after resection.

    View details for DOI 10.1245/s10434-014-4079-6

    View details for Web of Science ID 000350553100049

  • Accuracy of positron emission tomography in identifying hilar (N1) lymph node involvement in non-small cell lung cancer: Implications for stereotactic body radiation therapy. Practical radiation oncology Pepek, J. M., Marks, L. B., Berry, M. F., Ready, N. E., Gee, N. G., Coleman, R. E., D'Amico, T. A., Crawford, J., Kelsey, C. R. 2015; 5 (2): 79-84

    Abstract

    To assess the efficacy of preoperative positron emission tomography (PET) to stage the ipsilateral hilum in resected non-small cell lung cancer (NSCLC).All patients who underwent surgery for NSCLC between 1995 and 2008 were evaluated. Patients who underwent preoperative PET imaging at our institution and had hilar nodal sampling were included. Those whose primary tumors extended to the hilum or who received preoperative chemotherapy or radiation therapy were excluded. All PET studies were interpreted by an attending nuclear medicine radiologist and were scored as positive or negative in the hilum or peribronchial area based on visual analysis alone. A 2-sided Fisher exact test compared patient subgroups.During the time interval, 1558 patients underwent surgery for NSCLC, of whom 484 were eligible for this analysis. The ipsilateral hilum was positive on preoperative PET in 107 patients. The median number of N1 lymph nodes sampled was 4 (range, 1-31). Positive ipsilateral N1 lymph nodes were identified pathologically in 91 patients (19%). Among the 91 patients with involved N1 lymph nodes, 40 were PET positive resulting in a sensitivity of 44%. Among 393 patients without pathologic involvement of hilar lymph nodes, 326 were PET negative resulting in a specificity of 83%. The positive predictive and negative predictive values were 37% and 86%, respectively.Positron emission tomography appears to have limitations in staging the ipsilateral hilar lymph nodes. Invasive sampling is appropriate if treatment would differ based on the nodal status.

    View details for DOI 10.1016/j.prro.2014.05.002

    View details for PubMedID 25413417

  • Benefit of Adjuvant Chemotherapy After Resection of Stage II (T1-2N1M0) Non-Small Cell Lung Cancer in Elderly Patients. Annals of surgical oncology Berry, M. F., Coleman, B. K., Curtis, L. H., Worni, M., D'Amico, T. A., Akushevich, I. 2015; 22 (2): 642-648

    Abstract

    We evaluated the use and efficacy of adjuvant chemotherapy after resection of T1-2N1M0 non-small cell lung cancer (NSCLC) in elderly patients.Factors associated with the use of adjuvant chemotherapy in patients older than 65 years of age who underwent surgical resection of T1-2N1M0 NSCLC without induction chemotherapy or radiation in the Surveillance, Epidemiology, and End Results-Medicare database from 1992 to 2006 were assessed using a multivariable logistic regression model that included treatment, patient, tumor, and census tract characteristics. Overall survival (OS) was analyzed using the Kaplan-Meier approach and inverse probability weight-adjusted Cox proportional hazard models.Overall, 2,781 patients who underwent surgical resection as the initial treatment for T1-2N1M0 NSCLC and survived at least 31 days after surgery were identified, with adjuvant chemotherapy given to 784 patients (28.2 %). Factors that predicted adjuvant chemotherapy use were younger age and higher T status. The 5-year OS was significantly better for patients who received adjuvant chemotherapy compared with patients not given adjuvant chemotherapy: 35.8 % (95 % confidence interval [CI] 31.9-39.6) vs. 28.0 % (95 % CI 25.9-30.0) (p = 0.008). In the inverse probability weight-adjusted Cox proportional hazard regression model, adjuvant chemotherapy use predicted significantly improved survival (hazard ratio 0.84; 95 % CI 0.76-0.92; p = 0.0002).Adjuvant chemotherapy after resection of T1-2N1M0 NSCLC is associated with significantly improved survival in patients older than 65 years. These data can be used to provide elderly patients with realistic expectations of the potential benefits when considering adjuvant chemotherapy in this setting.

    View details for DOI 10.1245/s10434-014-4056-0

    View details for PubMedID 25192680

  • Defining the role of adjuvant chemotherapy after lobectomy for typical bronchopulmonary carcinoid tumors. Annals of thoracic surgery Nussbaum, D. P., Speicher, P. J., Gulack, B. C., Hartwig, M. G., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2015; 99 (2): 428-434

    Abstract

    Treatment guidelines for typical bronchopulmonary carcinoid tumors recommend observation alone after resection of stage I-IIIA disease, but there are limited data related to the use of adjuvant chemotherapy in the setting of nodal metastases found at operation.Patients in the National Cancer Data Base (NDCB) who underwent lobectomy for typical carcinoid and had metastatic nodal disease were stratified by the use of adjuvant chemotherapy. Baseline characteristics and outcomes were compared between groups. Next, patients were propensity matched using a 3:1 nearest-neighbor algorithm, and adjusted outcomes were compared. Finally, long-term survival was evaluated using the Kaplan-Meier method with comparisons based on the log-rank test.Overall, 4,612 patients were identified, among whom 629 (13.6%) had positive lymph nodes at the time of operation. Of them, adjuvant chemotherapy was used in 37 patients (5.9%). There were no baseline differences between patients who did and those who did not receive adjuvant chemotherapy. Patients treated with chemotherapy demonstrated a survival disadvantage at 5 years (69.7% versus 81.9%; p = 0.042). After propensity matching, all baseline characteristics between groups were highly similar. There remained a trend toward inferior 5-year survival for patients who received adjuvant chemotherapy, although the difference no longer met statistical significance (69.7% versus 80.9%; p = 0.096).Adjuvant chemotherapy is not associated with improved survival among patients who undergo lobectomy for typical carcinoids and nodal metastases. These data support current treatment guidelines.

    View details for DOI 10.1016/j.athoracsur.2014.08.030

    View details for PubMedID 25499480

  • Hyperbaric oxygen therapy for treatment of neurologic sequela after atrioesophageal fistula. Annals of thoracic surgery Hirji, S. A., Haney, J. C., Welsby, I., Lombard, F. W., Berry, M. F. 2015; 99 (2): 681-682

    Abstract

    Atrioesophageal fistula (AEF) is a rare complication after radiofrequency ablation for atrial fibrillation but is associated with high mortality, usually due to sepsis or neurologic injury. We report the case of a patient who presented with an AEF and dense neurologic deficits who had complete neurologic recovery after management with emergent surgical repair without the use of cardiopulmonary bypass and with implementation of postoperative hyperbaric oxygen therapy.

    View details for DOI 10.1016/j.athoracsur.2014.04.058

    View details for PubMedID 25639405

  • The prognostic importance of the number of dissected lymph nodes after induction chemoradiotherapy for esophageal cancer. Annals of thoracic surgery Hanna, J. M., Erhunmwunsee, L., Berry, M., D'Amico, T., Onaitis, M. 2015; 99 (1): 265-269

    Abstract

    Analyses of adequacy of lymph node dissection during resection of esophageal cancer are based on patients who have not undergone induction chemoradiotherapy. We sought to determine the minimum number of dissected lymph nodes necessary to ensure adequate staging after induction chemoradiotherapy.A prospectively maintained thoracic surgery database was queried to identify consecutive patients undergoing postinduction esophagectomy from 1996 to 2010. Cox proportional hazard and recursive partitioning survival analyses were performed.Complete lymph node data were available for 395 patients. Mean age was 59.5 years, and 64 patients (16%) were female. The median number of dissected lymph nodes was 8 (range, 0 to 63). When pathologic (p)T stage, pN stage, and the number of dissected lymph nodes were used as predictors, only pN stage (odds ratio, 1.3; 95% confidence interval, 1.2 to 1.7) and age (odds ratio, 1.03; 95% confidence interval, 1.01 to 1.04) independently predicted survival. Recursive partitioning was performed on 262 pN0 patients using T stage and the number of dissected lymph nodes as predictors. No pN0 patient with 28 lymph nodes dissected died during follow-up. For patients with fewer than 28 lymph nodes dissected, the next prognostic factor was T stage. For pT1-2 N0 patients, the number of lymph nodes dissected did not affect survival. For pT3-4 N0 patients, a significant survival decrement was noted for patients with fewer than 7 lymph nodes dissected compared with those with more than 7 lymph nodes dissected.T stage determines prognosis in postinduction pN0 patients with fewer than 28 lymph nodes evaluated. Postinduction pT3N0 patients with fewer than 7 lymph nodes evaluated are understaged.

    View details for DOI 10.1016/j.athoracsur.2014.08.073

    View details for PubMedID 25440285

  • Adjuvant Chemotherapy Is Associated with Improved Survival after Esophagectomy without Induction Therapy for Node-Positive Adenocarcinoma JOURNAL OF THORACIC ONCOLOGY Speicher, P. J., Englum, B. R., Ganapathi, A. M., Mulvihill, M. S., Hartwig, M. G., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2015; 10 (1): 181-188

    Abstract

    This study investigated adjuvant chemotherapy (AC) use after esophagectomy without induction therapy for node-positive (pN+) adenocarcinoma using the National Cancer Database, including the impact of complications related to surgery (CRS) on outcomes.Predictors of AC use in 1694 patients in the National Cancer Data Base who underwent R0 esophagectomy from 2003-2011 without induction therapy for pN+ adenocarcinoma of the middle or lower esophagus and survived more than 30 days were identified with multivariable logistic regression. The impact of AC on survival was estimated using Kaplan-Meier and Cox-proportional hazards methods.AC was given to 874 of 1694 (51.6%) patients; 618 (70.7%) AC patients received radiation. Older age (adjusted odds ratio [AOR] 0.58/decade, p < 0.001), longer travel distance (AOR 0.78 per 100 miles, p = 0.03) and CRS (AOR 0.45, p < 0.001) predicted that AC was not used. Patients given AC had better 5-year survival than patients not given AC (24.2% versus 14.9%, p < 0.001), and AC use predicted improved survival in multivariate analysis (hazard ratio 0.67, p = 0.008). Receiving radiation in addition to AC did not improve survival (p = 0.35). Although CRS was associated with worse survival, patients who had CRS but received AC had superior survival compared to patients who did not have CRS or get AC (p = 0.016).AC after esophagectomy is associated with improved survival but was only used in half of patients with pN+ esophageal adenocarcinoma. We also found that the addition of radiation to AC was not associated with a survival benefit. CRS predict worse long-term survival and lower the chance of getting AC, but even patients with CRS had improved survival when given AC.

    View details for DOI 10.1097/JTO.0000000000000384

    View details for Web of Science ID 000346986500024

  • Thoracoscopic Left Upper Lobectomy in Patients With Internal Mammary Artery Coronary Bypass Grafts ANNALS OF THORACIC SURGERY Shah, A. A., Worni, M., Onaitis, M. W., Balderson, S. S., Harpole, D. H., D'Amico, T. A., Berry, M. F. 2014; 98 (4): 1207-1213
  • Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008 DISEASES OF THE ESOPHAGUS Worni, M., Castleberry, A. W., Gloor, B., Pietrobon, R., Haney, J. C., D'Amico, T. A., Akushevich, I., Berry, M. F. 2014; 27 (7): 662-669

    Abstract

    We examined outcomes and trends in surgery and radiation use for patients with locally advanced esophageal cancer, for whom optimal treatment isn't clear. Trends in surgery and radiation for patients with T1-T3N1M0 squamous cell or adenocarcinoma of the mid or distal esophagus in the Surveillance, Epidemiology, and End Results database from 1998 to 2008 were analyzed using generalized linear models including year as predictor; Surveillance, Epidemiology, and End Results doesn't record chemotherapy data. Local treatment was unimodal if patients had only surgery or radiation and bimodal if they had both. Five-year cancer-specific survival (CSS) and overall survival (OS) were analyzed using propensity-score adjusted Cox proportional-hazard models. Overall 5-year survival for the 3295 patients identified (mean age 65.1 years, standard deviation 11.0) was 18.9% (95% confidence interval: 17.3-20.7). Local treatment was bimodal for 1274 (38.7%) and unimodal for 2021 (61.3%) patients; 1325 (40.2%) had radiation alone and 696 (21.1%) underwent only surgery. The use of bimodal therapy (32.8-42.5%, P = 0.01) and radiation alone (29.3-44.5%, P < 0.001) increased significantly from 1998 to 2008. Bimodal therapy predicted improved CSS (hazard ratios [HR]: 0.68, P < 0.001) and OS (HR: 0.58, P < 0.001) compared with unimodal therapy. For the first 7 months (before survival curve crossing), CSS after radiation therapy alone was similar to surgery alone (HR: 0.86, P = 0.12) while OS was worse for surgery only (HR: 0.70, P = 0.001). However, worse CSS (HR: 1.43, P < 0.001) and OS (HR: 1.46, P < 0.001) after that initial timeframe were found for radiation therapy only. The use of radiation to treat locally advanced mid and distal esophageal cancers increased from 1998 to 2008. Survival was best when both surgery and radiation were used.

    View details for DOI 10.1111/dote.12123

    View details for Web of Science ID 000341150600009

    View details for PubMedID 23937253

  • Outcomes after Pneumonectomy for Benign Disease: The Impact of Urgent Resection JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Klapper, J., Hirji, S., Hartwig, M. G., D'Amico, T. A., Harpole, D. H., Onaitis, M. W., Berry, M. F. 2014; 219 (3): 518-524

    Abstract

    Pneumonectomy for benign disease is often complicated by inflammatory processes that obscure operative planes. We reviewed our experience to evaluate the impact of requiring urgent or emergent pneumonectomy on outcomes.All pneumonectomies for benign conditions from 1997 to 2012 at a single institution were retrospectively reviewed. Mortality was assessed using multivariable logistic regression that included laterality, age, and surgery status, which was emergent if performed within 24 hours of initial evaluation, urgent if performed after 24 hours but within the same hospital stay, and otherwise elective.Among 42 pneumonectomies, completion pneumonectomy after previous ipsilateral lung resection was performed in 14 patients (33%). Resection was elective in 22 patients (52%), urgent in 12 (28%), and emergent in 8 (19%). The most common indication was for necrotic lung (n = 12; 29%). Muscle flaps were used in 26 patients (62%). Perioperative mortality for the entire cohort was 29% (n = 12) and was significantly higher when surgery was urgent (5 of 12; 42%) or emergent (5 of 8; 62.5%) compared with elective (2 of 22; 9.1%) (p = 0.03). Requiring urgent or emergent surgery remained a significant predictor of mortality in multivariable analysis (odds ratio 10.4, p = 0.01).Pneumonectomy for benign disease has significant risk for mortality, particularly when not performed electively. Although surgery cannot be planned in the setting of trauma or some situations of acute infection, patients known to have conditions that are likely to require pneumonectomy should be considered for surgery earlier in their disease course, before developing an acute problem that requires urgent or emergent resection.

    View details for DOI 10.1016/j.jamcollsurg.2014.01.062

    View details for Web of Science ID 000341415100025

    View details for PubMedID 24862885

  • Thoracoscopic Left Upper Lobectomy in Patients With Internal Mammary Artery Coronary Bypass Grafts. The Annals of thoracic surgery Shah, A. A., Worni, M., Onaitis, M. W., Balderson, S. S., Harpole, D. H., D'Amico, T. A., Berry, M. F. 2014

    Abstract

    This study examined outcomes of a technique for performing thoracoscopic left upper lobectomy (LUL) in patients with a previous left internal mammary artery (LIMA) coronary artery bypass graft, where a small wedge of lung parenchyma adjacent to the graft is left to avoid injury.All patients undergoing thoracoscopic LUL from 1999 to 2010 at a single institution were reviewed. Perioperative morbidity, cancer recurrence, and long-term survival were compared between patients who had (LIMA group) or did not have (control group) a previous LIMA graft.During the study period, 290 patients underwent thoracoscopic LUL; 14 (5%) had previous LIMA grafts. There was no perioperative mortality in the LIMA group versus 4 (1%) in the control group (p = 0.65). One patient (7%) in the LIMA group required conversion to thoracotomy, which was similar to the control group (n = 16, 6%; p = 0.83). Overall perioperative morbidity was also not different between the groups (LIMA 36% [5 of 14] versus control 29% [81 of 276], p = 0.61). No patient in the LIMA group had perioperative cardiac ischemia. For patients with lung cancer, 5-year survival (LIMA 50% vs control 63%, p = 0.23) and cancer recurrence rates (LIMA 27% (3 of 11) versus control 15% (36 of 242), p = 0.27) were not different between the groups. Only 1 LIMA recurrence was local, and it was not related to the parenchyma left on the LIMA graft.Thoracoscopic LUL can be performed safely in patients with LIMA bypass grafts. Leaving lung parenchyma on the graft may prevent injury and does not compromise oncologic outcomes in appropriately selected patients.

    View details for DOI 10.1016/j.athoracsur.2014.05.068

    View details for PubMedID 25110335

  • Induction Therapy Does Not Improve Survival for Clinical Stage T2N0 Esophageal Cancer JOURNAL OF THORACIC ONCOLOGY Speicher, P. J., Ganapathi, A. M., Englum, B. R., Hartwig, M. G., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2014; 9 (8): 1195-1201

    Abstract

    This study compared survival after initial treatment with esophagectomy as primary therapy to induction therapy followed by esophagectomy for patients with clinical T2N0 (cT2N0) esophageal cancer in the National Cancer Database (NCDB).Predictors of therapy selection for patients with cT2N0 esophageal cancer in the NCDB from 1998 to 2011 were identified with multivariable logistic regression. Survival was evaluated using Kaplan-Meier and Cox proportional hazards methods.Surgery was used in 42.9% (2057 of 4799) of cT2N0 patients. Of 1599 esophagectomy patients for whom treatment timing was recorded, induction therapy was used in 44.1% (688). Pretreatment staging was proven accurate in only 26.7% of patients (210 of 786) who underwent initial surgery without induction treatment and had complete pathologic data available: 41.6% (n = 327) were upstaged and 31.7% (n = 249) were downstaged. Adjuvant therapy (chemotherapy or radiation therapy) was given to 50.2% of patients treated initially with surgery who were found after resection to have nodal disease. There was no significant difference in long-term survival between strategies of primary surgery and induction therapy followed by surgery (median 41.1 versus 41.9 months, p = 0.51). In multivariable analysis, induction therapy was not independently associated with risk of death (hazard ratio [HR], 1.16, p = 0.32).Current clinical staging for early-stage esophageal cancer is highly inaccurate, with only a quarter of surgically resected cT2N0 patients found to have had accurate pretreatment staging. Induction therapy for patients with cT2N0 esophageal cancer in the NCDB is not associated with improved survival.

    View details for Web of Science ID 000340138700022

    View details for PubMedID 25157773

  • Thoracoscopic Approach to Lobectomy for Lung Cancer Does Not Compromise Oncologic Efficacy ANNALS OF THORACIC SURGERY Berry, M. F., D'Amico, T. A., Onaitis, M. W., Kelsey, C. R. 2014; 98 (1): 197-202

    Abstract

    We compared survival between video-assisted thoracoscopic surgery (VATS) and thoracotomy approaches to lobectomy for non-small cell lung cancer.Overall survival of patients who had lobectomy for any stage non-small cell lung cancer without previous chemotherapy or radiation from 1996 to 2008 was evaluated using the Kaplan-Meier method and multivariate Cox analysis. Propensity scoring was used to assess the impact of selection bias.Overall, 1,087 patients met inclusion criteria (610 VATS, 477 thoracotomy). Median follow-up was not significantly different between VATS and thoracotomy patients overall (53.4 versus 45.4 months, respectively; p=0.06) but was longer for thoracotomy for surviving patients (102.4 versus 67.9 months, p<0.0001). Thoracotomy patients had larger tumors (3.9±2.3 versus 2.8±1.5 cm, p<0.0001), and more often had higher stage cancers (50% [n=237] versus 71% [n=435] stage I, p<0.0001) compared with VATS patients. In multivariate analysis of all patients, thoracotomy approach (hazard ratio [HR] 1.22, p=0.01), increasing age (HR 1.02 per year, p<0.0001), pathologic stage (HR 1.45 per stage, p<0.0001), and male sex (HR 1.35, p=0.0001) predicted worse survival. In a cohort of 560 patients (311 VATS, 249 thoracotomy) who were assembled using propensity scoring and were similar in age, stage, tumor size, and sex, the operative approach did not impact survival (p=0.5), whereas increasing age (HR 1.02 per year, p=0.01), pathologic stage (HR 1.44 per stage, p<0.0001), and male sex (HR 1.29, p=0.01) predicted worse survival.The thoracoscopic approach to lobectomy for non-small cell lung cancer does not result in worse long-term survival compared with thoracotomy.

    View details for DOI 10.1016/j.athoracsur.2014.03.018

    View details for Web of Science ID 000338432600052

    View details for PubMedID 24820392

  • Sex differences in early outcomes after lung cancer resection: Analysis of the Society of Thoracic Surgeons General Thoracic Database JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Tong, B. C., Kosinski, A. S., Burfeind, W. R., Onaitis, M. W., Berry, M. F., Harpole, D. H., D'Amico, T. A. 2014; 148 (1): 13-18

    Abstract

    Women with lung cancer have superior long-term survival outcomes compared with men, independent of stage. The cause of this disparity is unknown. For patients undergoing lung cancer resection, these survival differences could be due, in part, to relatively better perioperative outcomes for women. This study was undertaken to determine differences in perioperative outcomes after lung cancer surgery on the basis of sex.The Society of Thoracic Surgeons' General Thoracic Database was queried for all patients undergoing resection of lung cancer between 2002 and 2010. Postoperative complications were analyzed with respect to sex. Univariable analysis was performed, followed by multivariable modeling to determine significant risk factors for postoperative morbidity and mortality.A total of 34,188 patients (16,643 men and 17,545 women) were considered. Univariable analysis demonstrated statistically significant differences in postoperative complications favoring women in all categories of postoperative complications. Women also had lower in-hospital and 30-day mortality (odds ratio, 0.56; 95% confidence interval, 0.44-0.71; P < .001). Multivariable analysis demonstrated that several preoperative conditions independently predicted 30-day mortality: male sex, increasing age, lower diffusion capacity, renal insufficiency, preoperative radiation therapy, cancer stage, extent of resection, and thoracotomy as surgical approach. Coronary artery disease was an independent predictor of mortality in women but not in men. Thoracotomy as the surgical approach and preoperative radiation therapy were predictive of mortality for men but not for women. Postoperative prolonged air leak and empyema predicted mortality in men but not in women.Women have lower postoperative morbidity and mortality after lung cancer surgery. Some risk factors are sex-specific with regard to mortality. Further study is warranted to determine the cause of these differences and to determine their effect on survival.

    View details for DOI 10.1016/j.jtcvs.2014.03.012

    View details for Web of Science ID 000340935300009

    View details for PubMedID 24726742

  • Discrete improvement in racial disparity in survival among patients with stage IV colorectal cancer: a 21-year population-based analysis. Journal of gastrointestinal surgery Castleberry, A. W., Güller, U., Tarantino, I., Berry, M. F., Brügger, L., Warschkow, R., Cerny, T., Mantyh, C. R., Candinas, D., Worni, M. 2014; 18 (6): 1194-1204

    Abstract

    Recently, multiple clinical trials have demonstrated improved outcomes in patients with metastatic colorectal cancer. This study investigated if the improved survival is race dependent.Overall and cancer-specific survival of 77,490 White and Black patients with metastatic colorectal cancer from the 1988-2008 Surveillance Epidemiology and End Results registry were compared using unadjusted and multivariable adjusted Cox proportional hazard regression as well as competing risk analyses.Median age was 69 years, 47.4 % were female and 86.0 % White. Median survival was 11 months overall, with an overall increase from 8 to 14 months between 1988 and 2008. Overall survival increased from 8 to 14 months for White, and from 6 to 13 months for Black patients. After multivariable adjustment, the following parameters were associated with better survival: White, female, younger, better educated and married patients, patients with higher income and living in urban areas, patients with rectosigmoid junction and rectal cancer, undergoing cancer-directed surgery, having well/moderately differentiated, and N0 tumors (p < 0.05 for all covariates). Discrepancies in overall survival based on race did not change significantly over time; however, there was a significant decrease of cancer-specific survival discrepancies over time between White and Black patients with a hazard ratio of 0.995 (95 % confidence interval 0.991-1.000) per year (p = 0.03).A clinically relevant overall survival increase was found from 1988 to 2008 in this population-based analysis for both White and Black patients with metastatic colorectal cancer. Although both White and Black patients benefitted from this improvement, a slight discrepancy between the two groups remained.

    View details for DOI 10.1007/s11605-014-2515-3

    View details for PubMedID 24733258

  • Discrete Improvement in Racial Disparity in Survival among Patients with Stage IV Colorectal Cancer: a 21-Year Population-Based Analysis JOURNAL OF GASTROINTESTINAL SURGERY Castleberry, A. W., Gueller, U., Tarantino, I., Berry, M. F., Bruegger, L., Warschkow, R., Cerny, T., Mantyh, C. R., Candinas, D., Worni, M. 2014; 18 (6): 1194-1204

    View details for DOI 10.1007/s11605-014-2515-3

    View details for Web of Science ID 000336393000016

    View details for PubMedID 24733258

  • The impact of pulmonary hypertension on morbidity and mortality following major lung resection 21st European Conference on General Thoracic Surgery Wei, B., D'Amico, T., Samad, Z., Hasan, R., Berry, M. F. OXFORD UNIV PRESS INC. 2014: 1028–33

    Abstract

    Pulmonary hypertension is considered a poor prognostic factor for or even a contraindication to major lung resection, but evidence for this claim is lacking. This study evaluates the impact of pulmonary hypertension on morbidity and mortality following pulmonary lobectomy.Adult patients who underwent a lobectomy for cancer and had a transthoracic echocardiogram (TTE) performed within the year prior to the operation were included. Pulmonary hypertension was defined as an estimated right ventricular systolic pressure (RVSP) of ≥36 mmHg by TTE. The preoperative characteristics, intraoperative data and postoperative outcomes of patients with and those without pulmonary hypertension based on TTE were compared. A model for morbidity including published risk factors as well as pulmonary hypertension was developed by multivariable logistic regression.There were 279 patients without pulmonary hypertension and 19 patients with pulmonary hypertension. Patients with pulmonary hypertension had a lower preoperative forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide than patients without pulmonary hypertension and a higher incidence of tricuspid regurgitation and mitral regurgitation, but the groups were otherwise similar. The mean RVSP in the group of patients with pulmonary hypertension was 47 mmHg. Perioperative mortality (0.0 vs 2.9%; P = 1.0) and postoperative complications (57.9 vs 47.7%; P = 0.48) were not significantly different between patients with and those without pulmonary hypertension. The presence of pulmonary hypertension was not a predictor of adverse outcomes in either univariate or multivariate analysis.Lobectomy may be performed safely in selected patients with pulmonary hypertension, with complication rates comparable with those experienced by patients without pulmonary hypertension.

    View details for DOI 10.1093/ejcts/ezt495

    View details for Web of Science ID 000336997100020

    View details for PubMedID 24132298

  • Surgical Management of Congenital Pulmonary Malformations After the First Decade of Life ANNALS OF THORACIC SURGERY Wang, A., D'Amico, T. A., Berry, M. F. 2014; 97 (6): 1933-1938

    Abstract

    Most congenital pulmonary malformations are discovered early in life, but some are diagnosed in adulthood. We evaluated patients treated surgically after the first decade of life.All patients who underwent surgical treatment for a congenital pulmonary malformation diagnosed after 10 years of age at a single institution from 1997 to 2012 were evaluated for presenting symptoms, surgical management, perioperative outcomes, and symptom resolution.Twenty-two patients met the inclusion criteria. The most common malformations were pulmonary sequestration (n = 12, 55%), congenital cystic adenomatoid malformation (n = 2, 9%), and bronchial agenesis (n = 2, 9%). The median age at diagnosis was 36 years (range, 10-66 years). The most common presenting symptoms were dyspnea (n = 6, 27%) and hemoptysis (n = 4; 18%); 4 (18%) asymptomatic patients received diagnoses. The median duration of symptoms before operation was 14 months. An emergency room visit or hospitalization occurred in 11 patients (50%) before their referral for surgical evaluation. The surgical approach was thoracotomy for 7 patients (32%) and thoracoscopy for 15 patients (68%). All vascular anomalies requiring a pneumonectomy (n = 3, 14%) were done by a thoracotomy, and 83% (10/12) of pulmonary sequestrations were treated thoracoscopically. The median hospital stay was 3 days. There were no perioperative deaths, and minor morbidity occurred in 4 patients (18%). Complete resolution of symptoms after operation occurred in 94% (16/17) of patients, with a median follow-up time of 3 weeks.Early surgical management of congenital pulmonary malformations found after the first decade of life is recommended to control symptoms and avoid hospitalizations. Most adult pulmonary sequestrations can be treated with minimally invasive techniques.

    View details for DOI 10.1016/j.athoracsur.2014.01.053

    View details for Web of Science ID 000337252200012

    View details for PubMedID 24681038

  • Esophageal cancer: staging system and guidelines for staging and treatment JOURNAL OF THORACIC DISEASE Berry, M. F. 2014; 6: S289-S297

    Abstract

    Survival of esophageal cancer is improving but remains poor. Esophageal cancer stage is based on depth of tumor invasion, involvement of regional lymph nodes, and the presence or absence of metastatic disease. Appropriate work-up is critical to identify accurate pre-treatment staging so that both under-treatment and unnecessary treatment is avoided. Treatment strategy should follow guideline recommendations, and generally should be developed after multidisciplinary evaluation.

    View details for DOI 10.3978/j.issn.2072-1439.2014.03.11

    View details for Web of Science ID 000338282200002

    View details for PubMedID 24876933

  • The Utility of Pulmonary Function Tests in Predicting Pulmonary Outcomes Following Destination Therapy Left Ventricular Assist Device Placement 34th Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation Schechter, M. A., Castleberry, A. W., Kuchibhatla, M., Patel, C. B., Blue, L. J., Rogers, J. G., Berry, M. F., Schroder, J. N., Milano, C. A. ELSEVIER SCIENCE INC. 2014: S60–S60
  • Differential prognostic significance of extralobar and intralobar nodal metastases in patients with surgically resected stage II non-small cell lung cancer JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Haney, J. C., Hanna, J. M., Berry, M. F., Harpole, D. H., D'Amico, T. A., Tong, B. C., Onaitis, M. W. 2014; 147 (4): 1164-1168

    Abstract

    We sought to determine the prognostic significance of extralobar nodal metastases versus intralobar nodal metastases in patients with lung cancer and pathologic stage N1 disease.A retrospective review of a prospectively maintained lung resection database identified 230 patients with pathologic stage II, N1 non-small cell lung cancer from 1997 to 2011. The surgical pathology reports were reviewed to identify the involved N1 stations. The outcome variables included recurrence and death. Univariate and multivariate analyses were performed using the R statistical software package.A total of 122 patients had extralobar nodal metastases (level 10 or 11); 108 patients were identified with intralobar nodal disease (levels 12-14). The median follow-up was 111 months. The baseline characteristics were similar in both groups. No significant differences were noted in the surgical approach, anatomic resections performed, or adjuvant therapy rates between the 2 groups. Overall, 80 patients developed recurrence during follow-up: 33 (30%) of 108 in the intralobar and 47 (38%) of 122 in the extralobar cohort. The median overall survival was 46.9 months for the intralobar cohort and 24.4 months for the extralobar cohort (P < .001). In a multivariate Cox proportional hazard model that included the presence of extralobar nodal disease, age, tumor size, tumor histologic type, and number of positive lymph nodes, extralobar nodal disease independently predicted both recurrence-free and overall survival (hazard ratio, 1.96; 95% confidence interval, 1.36-2.81; P = .001).In patients who underwent surgical resection for stage II non-small cell lung cancer, the presence of extralobar nodal metastases at level 10 or 11 predicted significantly poorer outcomes than did nodal metastases at stations 12 to 14. This finding has prognostic importance and implications for adjuvant therapy and surveillance strategies for patients within the heterogeneous stage II (N1) category.

    View details for DOI 10.1016/j.jtcvs.2013.12.015

    View details for Web of Science ID 000332772200019

    View details for PubMedID 24507984

  • Survival in the Elderly after Pneumonectomy for Early-Stage Non-Small Cell Lung Cancer: A Comparison with Nonoperative Management JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Speicher, P. J., Ganapathi, A. M., Englum, B. R., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2014; 218 (3): 439-449

    Abstract

    Short-term outcomes of morbidity, mortality, and quality of life after pneumonectomy worsen with increasing age. The impact of age on long-term outcomes has not been well described. The purpose of this study was to quantify the impact of patient age on long-term survival after pneumonectomy for early-stage non-small cell lung cancer.Overall survival (OS) of patients who had a pneumonectomy for stage I to II non-small cell lung cancer in the Surveillance Epidemiology and End Results program registry from 1988 through 2010 was evaluated using multivariable and propensity score adjusted Cox proportional hazard models. Age was stratified as younger than 50 years, 50 to 69 years, 70 to 79 years, and 80 years and older. Pneumonectomy patients' OS was compared with matched patients who refused surgery and underwent radiation therapy (RT).Pneumonectomies comprised 10.8% of non-small cell lung cancer resections in 1988, but only 2.9% in 2010. Overall, 5-year OS of 5,701 pneumonectomy patients was 49.8% (95% CI, 45.3-54.8%) for patients younger than 50 years, 40.5% (95% CI, 38.8-42.2%) for patients 50 to 69 years, 28.9% (95% CI, 26.6-31.5%) for patients 70 to 79 years, and 18.8% (95% CI, 14.2-24.8%) for patients 80 and older (p < 0.001). Increasing patient age was the most important predictor of worse OS (hazard ratio = 1.34 per decade; p < 0.001). For patients younger than 70 years, 5-year OS was 46.3% (95% CI, 36.2-59.2%) after pneumonectomy vs 18.4% (95% CI, 11.9-28.3%) for matched RT patients (p < 0.001). In matched groups of patients 70 years and older, 5-year OS for pneumonectomy was 25.8% (95% CI, 20.8-32.0%) vs 12.2% for RT (95% CI, 8.6-17.4%; p = 0.02).Survival after pneumonectomy for stage I to II non-small cell lung cancer decreases steadily with patient age. The incremental benefit of pneumonectomy vs RT in matched patients is less in patients older than 70 years than in younger patients, although outcomes with pneumonectomy are superior to RT in all age groups. Patients should not be denied pneumonectomy based on age alone, but careful patient selection in elderly patients is essential to optimize survival.

    View details for DOI 10.1016/j.jamcollsurg.2013.12.005

    View details for Web of Science ID 000331718400020

    View details for PubMedID 24559956

  • Pneumonectomy for Stage IIIA NSCLC: A Chance, Not a Calamity Reply ANNALS OF THORACIC SURGERY Shah, A. A., D'Amico, T. A., Berry, M. F. 2014; 97 (1): 382-383
  • Reply: To PMID 23545195. Annals of thoracic surgery Shah, A. A., D'Amico, T. A., Berry, M. F. 2014; 97 (1): 382-383

    View details for DOI 10.1016/j.athoracsur.2013.09.056

    View details for PubMedID 24384211

  • Sleeve Lobectomy for Non-Small Cell Lung Cancer With N1 Nodal Disease Does Not Compromise Survival ANNALS OF THORACIC SURGERY Berry, M. F., Worni, M., Wang, X., Harpole, D. H., D'Amico, T. A., Onaitis, M. W. 2014; 97 (1): 230-235

    Abstract

    We evaluated if sleeve lobectomy had worse survival compared with pneumonectomy for non-small cell lung cancer (NSCLC) with N1 disease, which may be a risk factor for locoregional recurrence.Patients who underwent pneumonectomy or sleeve lobectomy without induction treatment for T2-3 N1 M0 NSCLC at a single institution from 1999 to 2011 were reviewed. Survival distribution was estimated with the Kaplan-Meier method, and multivariable Cox proportional hazards regression was used to evaluate the effect of resection extent on survival.During the study period, 87 patients underwent pneumonectomy (52 [60%]) or sleeve lobectomy (35 [40%]) for T2-3 N1 M0 NSCLC. Pneumonectomy and sleeve lobectomy patients had similar mean ages (60.9 ± 10.7 vs 63.5 ± 12.7 years, p = 0.30), gender distribution (69.2% [36 of 52] vs 60.0% [21 of 35] male, p = 0.37), mean forced expiratory volume in 1 second (66.3 ± 15.9 vs 63.5 ± 17.6, p = 0.47), stage (61.5% [32 of 52] vs 62.9% [22 of 35] stage II, p = 0.90), and tumor grade (51.9% [27 of 52] vs 31.4% [11 of 35] well/moderately differentiated, p = 0.17). Postoperative mortality (3.8% [2 of 52] vs 5.7% [2 of 35], p = 0.68) and median (interquartile range) length of stay (5 [4 to 7] vs 5 [4 to 7] days, p = 0.68) were similar between the two groups. The 3-year survival after pneumonectomy (46.8% [95% CI, 31.8% to 60.4%]) and sleeve lobectomy (65.2% [95% CI, 45.5% to 79.3%]) was not significantly different (p = 0.23). In multivariable survival analysis that included resection extent, age, stage, and grade, only increasing age predicted worse survival (hazard ratio, 1.03/year; p = 0.03).Performing sleeve lobectomy instead of pneumonectomy for NSCLC with N1 nodal disease does not compromise long-term survival.

    View details for DOI 10.1016/j.athoracsur.2013.09.016

    View details for Web of Science ID 000329155900043

    View details for PubMedID 24206972

  • Reply: To PMID 23063200. Annals of thoracic surgery Berry, M. F., Martin, J. T., D'Amico, T. A. 2013; 96 (5): 1911-?

    View details for DOI 10.1016/j.athoracsur.2013.07.041

    View details for PubMedID 24182495

  • Management of T2N0 Esophageal Cancer Reply ANNALS OF THORACIC SURGERY Berry, M. F., Martin, J. T., D'Amico, T. A. 2013; 96 (5): 1911-1911
  • Contraindications of video-assisted thoracoscopic surgical lobectomy and determinants of conversion to open JOURNAL OF THORACIC DISEASE Hanna, J. M., Berry, M. F., D'Amico, T. A. 2013; 5: S182-S189

    Abstract

    Since the introduction of anatomic lung resection by video-assisted thoracoscopic surgery (VATS) was introduced 20 years ago, VATS has experienced major advances in both equipment and technique, introducing a technical challenge in the surgical treatment of both benign and malignant lung disease. The demonstrated safety, decreased morbidity, and equivalent efficacy of this minimally invasive technique has led to the acceptance of VATS as a standard surgical modality for early-stage lung cancer and increasing application to more advanced disease. However, only a minority of lobectomies are performed using the VATS technique, likely owing to concern for intraoperative complications. Optimal operative planning, including obtaining baseline pulmonary function tests with diffusion measurements, positron emission tomography and/or computed tomography scans, bronchoscopy, and endobronchial ultrasound or mediastinoscopy, can be used to anticipate and potentially prevent the occurrence of complications. With increasing focus on operative planning, as well as comfort and experience with the VATS technique, the indications for which this technique is used has grown. As such, the absolute contraindications have narrowed to inability to tolerate single lung ventilation, inability to achieve complete resection with lobectomy, T3 or T4 tumors, and N2 or N3 disease. However, as VATS lobectomy has been applied to more advanced stage disease, the rate of conversion to open thoracotomy has increased, particularly early in the surgeon's learning curve. Causes of conversion are generally classified into four categories: intraoperative complications, technical problems, anatomical problems, and oncological conditions. Though it is difficult to anticipate which patients may require conversion, it appears that these patients do not suffer from increased morbidity or mortality as a result of conversion to open thoracotomy. Therefore, with a focus on a safe and complete resection, conversion should be regarded as a means of completing resections in a traditional manner rather than as a surgical failure.

    View details for DOI 10.3978/j.issn.2072-1439.2013.07.08

    View details for Web of Science ID 000324675700005

    View details for PubMedID 24040521

  • Treatment Modalities for T1N0 Esophageal Cancers A Comparative Analysis of Local Therapy Versus Surgical Resection JOURNAL OF THORACIC ONCOLOGY Berry, M. F., Zeyer-Brunner, J., Castleberry, A. W., Martin, J. T., Gloor, B., Pietrobon, R., D'Amico, T. A., Worni, M. 2013; 8 (6): 796-802

    Abstract

    To investigate the role of nonsurgical treatment for early-stage esophageal cancer, we compared the outcomes of local therapy to esophagectomy, using a large, national database.Five-year cancer-specific and overall survival (OS) of patients, with T1N0M0 squamous cell or adenocarcinoma of the mid or distal esophagus treated with either surgery or local therapy, with ablative and/or excision techniques, in the Surveillance Epidemiology and End Results cancer registry from 1998 to 2008, were compared using the Kaplan-Meier approach, and multivariable and propensity-score adjusted Cox proportional hazard, and competing risk models.Of 1458 patients with T1N0 esophageal cancer, 1204 (83%) had surgery and 254 (17%) had local therapy only. The use of local therapy increased significantly from 8.1% in 1998 to 24.1% in 2008 (p < 0.001). The 5-year OS after local excisional therapy and surgery was not significantly different (55.5% versus 64.1% respectively, p = 0.07), and 5-year cancer-specific survival (CSS) also did not differ (81.7% versus 75.8%, p = 0.10). However, after propensity-score adjustment, CSS was better for patients who underwent local therapy compared with those who underwent surgery (hazard ratio: 0.46, 95% confidence interval: 0.27-0.77, p = 0.003), whereas OS remained similar.The use of local therapy for T1N0 esophageal cancers increased significantly from 1998 to 2008. Compared with those treated with esophagectomy, patients treated with local therapy had similar OS but improved CSS, indicating a higher chance of dying from other causes. Further studies are needed to confirm the oncologic efficacy of local therapy when used in patients whose lifespans are not limited by conditions other than esophageal cancer.

    View details for DOI 10.1097/JTO.0b013e3182897bf1

    View details for Web of Science ID 000319258000021

    View details for PubMedID 24614244

  • Variability in the Treatment of Elderly Patients with Stage IIIA (N2) Non-Small-Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Berry, M. F., Worni, M., Pietrobon, R., D'Amico, T. A., Akushevich, I. 2013; 8 (6): 744-752

    Abstract

    : We evaluated treatment patterns of elderly patients with stage IIIA (N2) non-small-cell lung cancer (NSCLC).: The use of surgery, chemotherapy, and radiation for patients with stage IIIA (T1-T3N2M0) NSCLC in the Surveillance, Epidemiology, and End Results-Medicare database from 2004 to 2007 was analyzed. Treatment variability was assessed using a multivariable logistic regression model that included treatment, patient, tumor, and census track variables. Overall survival was analyzed using the Kaplan-Meier approach and Cox proportional hazard models.: The most common treatments for 2958 patients with stage IIIA (N2) NSCLC were radiation with chemotherapy (n = 1065, 36%), no treatment (n = 534, 18%), and radiation alone (n = 383, 13%). Surgery was performed in 709 patients (24%): 235 patients (8%) had surgery alone, 40 patients (1%) had surgery with radiation, 222 patients had surgery with chemotherapy (8%), and 212 patients (7%) had surgery, chemotherapy, and radiation. Younger age (p < 0.0001), lower T-status (p < 0.0001), female sex (p = 0.04), and living in a census track with a higher median income (p = 0.03) predicted surgery use. Older age (p < 0.0001) was the only factor that predicted that patients did not get any therapy. The 3-year overall survival was 21.8 ± 1.5% for all patients, 42.1 ± 3.8% for patients that had surgery, and 15.4 ± 1.5% for patients that did not have surgery. Increasing age, higher T-stage and Charlson Comorbidity Index, and not having surgery, radiation, or chemotherapy were all risk factors for worse survival (all p values < 0.001).: Treatment of elderly patients with stage IIIA (N2) NSCLC is highly variable and varies not only with specific patient and tumor characteristics but also with regional income level.

    View details for DOI 10.1097/JTO.0b013e31828916aa

    View details for Web of Science ID 000319258000013

    View details for PubMedID 23571473

  • Diabetes mellitus: A significant co-morbidity in the setting of lung cancer? THORACIC CANCER Washington, I., Chino, J. P., Marks, L. B., D'Amico, T. A., Berry, M. F., Ready, N. E., Higgins, K. A., Yoo, D. S., Kelsey, C. R. 2013; 4 (2): 123-130
  • The Role of Radiation Therapy in Resected T2 N0 Esophageal Cancer: A Population-Based Analysis ANNALS OF THORACIC SURGERY Martin, J. T., Worni, M., Zwischenberger, J. B., Gloor, B., Pietrobon, R., D'Amico, T. A., Berry, M. F. 2013; 95 (2): 453-458

    Abstract

    The prognosis of even early-stage esophageal cancer is poor. Because there is not a consensus on how to manage T2 N0 disease, we examined survival after resection of T2 N0 esophageal cancer, with or without radiation therapy.Patients who underwent resection for T2 N0 squamous cell carcinoma or adenocarcinoma of the mid or distal esophagus, with or without radiation therapy, were identified using the Surveillance, Epidemiology and End Results cancer registry from 1998 to 2008. The 5-year cancer-specific survival (CSS) and overall survival (OS) after resection alone and combined resection with radiation therapy were compared using the Kaplan-Meier approach, risk-adjusted Cox proportional hazard models, and competing risk models.The 5-year OS of 490 T2 N0 patients was 40.3% (95% confidence interval [CI], 35.2% to 45.4%). Surgical resection alone was used in 267 patients (54%) and combined therapy in 223 (46%). The 5-year OS was 38.6% (95% CI, 31.7% to 45.5%) in patients undergoing resection only and 42.3% (95% CI, 34.7% to 49.6%) for combined therapy (p = 0.48). No difference in OS was found, even after risk adjustment (hazard ratio [HR], 1.14; 95% CI, 0.87 to 1.48; p = 0.35). However, in landmark studies with left truncation for 3 and 6 months, resection only showed better OS than combined therapy (HR, 1.33; 95% CI, 1.01 to 1.75; p = 0.04 vs HR, 1.36; 95% CI, 1.01 to 1.83; p = 0.04, respectively). No such difference for CSS was detected, even for the landmark study after 6 months (HR, 1.16; 95% CI, 0.98 to 1.39, p = 0.09).Combining radiation therapy with esophagectomy did not result in improved outcomes compared with esophagectomy alone for patients with T2 N0 esophageal cancer in the Surveillance, Epidemiology and End Results database.

    View details for DOI 10.1016/j.athoracsur.2012.08.049

    View details for Web of Science ID 000313792000021

    View details for PubMedID 23063200

  • Does Surgery Improve Outcomes for Esophageal Squamous Cell Carcinoma? An Analysis Using the Surveillance Epidemiology and End Results Registry from 1998 to 2008 JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Worni, M., Martin, J., Gloor, B., Pietrobon, R., D'Amico, T. A., Akushevich, I., Berry, M. F. 2012; 215 (5): 643-651

    Abstract

    We examined survival associated with locally advanced esophageal squamous cell cancer (SCC) to evaluate if treatment without surgery could be considered adequate.Patients in the Surveillance, Epidemiology and End Results Registry (SEER) registry with stage II-III SCC of the mid or distal esophagus from 1998-2008 were grouped by treatment with definitive radiation versus esophagectomy with or without radiation. Information on chemotherapy is not recorded in SEER. Tumor stage was defined as first clinical tumor stage in case of neo-adjuvant therapy and pathological report if no neo-adjuvant therapy was performed. Cancer-specific (CSS) and overall survival (OS) were analyzed using the Kaplan-Meier approach and propensity-score adjusted Cox proportional hazard models.Of the 2,431 patients analyzed, there were 844 stage IIA (34.7%), 428 stage IIB (17.6%), 1,159 stage III (47.7%) patients. Most were treated with definitive radiation (n = 1,426, 58.7%). Of the 1,005 (41.3%) patients who underwent surgery, 369 (36.7%) had preoperative radiation, 160 (15.9%) had postoperative radiation, and 476 (47.4%) had no radiation. Five-year survival was 17.9% for all patients, and 22.1%, 18.5%, and 14.5% for stages IIA, IIB, and stage III, respectively. Compared to treatment that included surgery, definitive radiation alone predicted worse propensity-score adjusted survival for all patients (CSS Hazard Ratio [HR] 1.48, p < 0.001; OS HR 1.46, p < 0.001) and for stage IIA, IIB, and III patients individually (all p values ≤ 0.01). Compared to surgery alone, surgery with radiation predicted improved survival for stage III patients (CSS HR 0.62, p = 0.001, OS HR 0.62, p < 0.001) but not stage IIA or IIB (all p values > 0.18).Esophagectomy is associated with improved survival for patients with locally advanced SCC and should be considered as an integral component of the treatment algorithm if feasible.

    View details for DOI 10.1016/j.jamcollsurg.2012.07.006

    View details for Web of Science ID 000311575600008

    View details for PubMedID 23084493

  • Thoracoscopic Lobectomy Has Increasing Benefit in Patients With Poor Pulmonary Function A Society of Thoracic Surgeons Database Analysis ANNALS OF SURGERY Ceppa, D. P., Kosinski, A. S., Berry, M. F., Tong, B. C., Harpole, D. H., Mitchell, J. D., D'Amico, T. A., Onaitis, M. W. 2012; 256 (3): 487-493

    Abstract

    Using a national database, we asked whether video-assisted thoracoscopic surgery (VATS) lobectomy is beneficial in high-risk pulmonary patients.Single-institution series demonstrated benefit of VATS lobectomy over lobectomy via thoracotomy in poor pulmonary function patients [FEV1 (forced expiratory volume in 1 second) or DLCO (diffusion capacity of the lung to carbon monoxide) <60% predicted].The STS General Thoracic Database was queried for patients having undergone lobectomy by either thoracotomy or VATS between 2000 and 2010. Postoperative pulmonary complications included those defined by the STS database.In the STS database, 12,970 patients underwent lobectomy (thoracotomy, n = 8439; VATS, n = 4531) and met inclusion criteria. The overall rate of pulmonary complications was 21.7% (1832/8439) and 17.8% (806/4531) in patients undergoing lobectomy with thoracotomy and VATS, respectively (P < 0.0001). In a multivariable model of pulmonary complications, thoracotomy approach (OR = 1.25, P < 0.001), decreasing FEV1% predicted (OR = 1.01 per unit, P < 0.001) and DLCO% predicted (OR = 1.01 per unit, P < 0.001), and increasing age (1.02 per year, P < 0.001) independently predicted pulmonary complications. When examining pulmonary complications in patients with FEV1 less than 60% predicted, thoracotomy patients have markedly increased pulmonary complications when compared with VATS patients (P = 0.023). No significant difference is noted with FEV1 more than 60% predicted.Poor pulmonary function predicts respiratory complications regardless of approach. Respiratory complications increase at a significantly greater rate in lobectomy patients with poor pulmonary function after thoracotomy compared with VATS. Planned surgical approach should be considered while determining whether a high-risk patient is an appropriate resection candidate.

    View details for DOI 10.1097/SLA.0b013e318265819c

    View details for Web of Science ID 000308670900021

    View details for PubMedID 22868367

  • Lymphovascular Invasion in Non-Small-Cell Lung Cancer Implications for Staging and Adjuvant Therapy JOURNAL OF THORACIC ONCOLOGY Higgins, K. A., Chino, J. P., Ready, N., D'Amico, T. A., Berry, M. F., Sporn, T., Boyd, J., Kelsey, C. R. 2012; 7 (7): 1141-1147

    Abstract

    Lymphovascular space invasion (LVI) is an established negative prognostic factor and an indication for postoperative radiation therapy in many malignancies. The purpose of this study was to evaluate LVI in patients with early-stage non-small-cell lung cancer, undergoing surgical resection.All patients who underwent initial surgery for pT1-3N0-2 non-small-cell lung cancer at Duke University Medical Center from 1995 to 2008 were identified. A multivariate ordinal regression was used to assess the relationship between LVI and pathologic hilar and/or mediastinal lymph node (LN) involvement. A multivariate Cox regression analysis was used to evaluate the relationship of LVI and other clinical and pathologic factors on local failure (LF), freedom from distant metastasis (FFDM), and overall survival (OS). Kaplan-Meier methods were used to generate estimates of LF, FFDM, and OS in patients with and without LVI.One thousand five hundred and fifty-nine patients were identified. LVI was independently associated with the presence of regional LN involvement (p < 0.001) along with lobar (versus sublobar) resections (p < 0.001), and an open thoracotomy (versus video-assisted thoracoscopic surgery). LVI was not independently associated with LF on multivariate analysis (hazard ratio [HR] = 1.23, p = 0.25), but was associated with a lower FFDM (HR 1.52, p = 0.005) and OS (HR 1.26, p = 0.015). In addition, multivariate analysis showed that LVI was strongly associated with increased risk of developing distant metastases (HR = 1.75, p = 0.006) and death (HR = 1.53, p = 0.003) in adenocarcinomas but not in squamous carcinomas.LVI is associated with an increased risk of harboring regional LN involvement. LVI is also an adverse prognostic factor for the development of distant metastases and long-term survival.

    View details for DOI 10.1097/JTO.0b013e3182519a42

    View details for Web of Science ID 000306458700114

    View details for PubMedID 22617241

  • Is radiation without surgery the adequate therapy for potentially resectable esophageal squamous cell carcinoma? An analysis using the Surveillance Epidemiology, and End Results Registry from 1998 to 2008 99th Annual Congress of the Swiss-Society-of-Surgery Worni, M., Gloor, B., Pietrobon, R., D'Amico, T. A., Akushevich, I., Berry, M. F. WILEY-BLACKWELL. 2012: 8–8
  • Induction Chemoradiation Is Not Superior to Induction Chemotherapy Alone in Stage IIIA Lung Cancer ANNALS OF THORACIC SURGERY Shah, A. A., Berry, M. F., Tzao, C., Gandhi, M., Worni, M., Pietrobon, R., D'Amico, T. A. 2012; 93 (6): 1807-1812

    Abstract

    The optimal treatment strategy for patients with operable stage IIIA (N2) non-small cell lung cancer is uncertain. We performed a systematic review and meta-analysis to test the hypothesis that the addition of radiotherapy to induction chemotherapy prior to surgical resection does not improve survival compared with induction chemotherapy alone.A comprehensive search of PubMed for relevant studies comparing patients with stage IIIA (N2) non-small cell lung cancer undergoing resection after treatment with induction chemotherapy alone or induction chemoradiotherapy was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Hazard ratios were extracted from these studies to give pooled estimates of the effect of induction therapy on overall survival.There were 7 studies that met criteria for analysis, including 1 randomized control trial, 1 phase II study, 3 retrospective reviews, and 2 published abstracts of randomized controlled trials. None of the studies demonstrated a survival benefit to adding induction radiation to induction chemotherapy versus induction chemotherapy alone. The meta-analysis performed on randomized studies (n=156 patients) demonstrated no benefit in survival from adding radiation (hazard ratio 0.93, 95% confidence interval 0.54 to 1.62, p=0.81), nor did the meta-analysis performed on retrospective studies (n=183 patients, hazard ratio 0.77, 95% confidence interval 0.50 to 1.19, p=0.24).Published evidence is sparse but does not support the use of radiation therapy in induction regimens for stage IIIA (N2). Given the potential disadvantages of adding radiation preoperatively, clinicians should consider using this treatment strategy only in the context of a clinical trial to allow better assessment of its effectiveness.

    View details for DOI 10.1016/j.athoracsur.2012.03.018

    View details for Web of Science ID 000304460000017

    View details for PubMedID 22632486

  • Local Failure in Resected N1 Lung Cancer: Implications for Adjuvant Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Higgins, K. A., Chino, J. P., Berry, M., Ready, N., Boyd, J., Yoo, D. S., Kelsey, C. R. 2012; 83 (2): 727-733

    Abstract

    To evaluate actuarial rates of local failure in patients with pathologic N1 non-small-cell lung cancer and to identify clinical and pathologic factors associated with an increased risk of local failure after resection.All patients who underwent surgery for non-small-cell lung cancer with pathologically confirmed N1 disease at Duke University Medical Center from 1995-2008 were identified. Patients receiving any preoperative therapy or postoperative radiotherapy or with positive surgical margins were excluded. Local failure was defined as disease recurrence within the ipsilateral hilum, mediastinum, or bronchial stump/staple line. Actuarial rates of local failure were calculated with the Kaplan-Meier method. A Cox multivariate analysis was used to identify factors independently associated with a higher risk of local recurrence.Among 1,559 patients who underwent surgery during the time interval, 198 met the inclusion criteria. Of these patients, 50 (25%) received adjuvant chemotherapy. Actuarial (5-year) rates of local failure, distant failure, and overall survival were 40%, 55%, and 33%, respectively. On multivariate analysis, factors associated with an increased risk of local failure included a video-assisted thoracoscopic surgery approach (hazard ratio [HR], 2.5; p = 0.01), visceral pleural invasion (HR, 2.1; p = 0.04), and increasing number of positive N1 lymph nodes (HR, 1.3 per involved lymph node; p = 0.02). Chemotherapy was associated with a trend toward decreased risk of local failure that was not statistically significant (HR, 0.61; p = 0.2).Actuarial rates of local failure in pN1 disease are high. Further investigation of conformal postoperative radiotherapy may be warranted.

    View details for DOI 10.1016/j.ijrobp.2011.07.018

    View details for Web of Science ID 000303920800059

    View details for PubMedID 22208965

  • Outcomes after treatment of resectable, node-negative esophageal cancer: A risk-adjusted analysis of the Surveillance, Epidemiology, and End Results registry 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Martin, J. T., Worni, M., Zwischenberger, J. B., Pietrobon, R., D'Amico, T. A., Berry, M. F. AMER SOC CLINICAL ONCOLOGY. 2012
  • Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell-derived factor 1 alpha angiogenic therapy for acute myocardial infarction in a murine model 37th Annual Meeting of the Western-Thoracic-Surgical-Association Hiesinger, W., Brukman, M. J., McCormick, R. C., Fitzpatrick, J. R., Frederick, J. R., Yang, E. C., Muenzer, J. R., Marotta, N. A., Berry, M. F., Atluri, P., Woo, Y. J. MOSBY-ELSEVIER. 2012: 962–66

    Abstract

    Ventricular remodeling after myocardial infarction begins with massive extracellular matrix deposition and resultant fibrosis. This loss of functional tissue and stiffening of myocardial elastic and contractile elements starts the vicious cycle of mechanical inefficiency, adverse remodeling, and eventual heart failure. We hypothesized that stromal cell-derived factor 1α (SDF-1α) therapy to microrevascularize ischemic myocardium would rescue salvageable peri-infarct tissue and subsequently improve myocardial elasticity.Immediately after left anterior descending coronary artery ligation, mice were randomly assigned to receive peri-infarct injection of either saline solution or SDF-1α. After 6 weeks, animals were killed and samples were taken from the peri-infarct border zone and the infarct scar, as well as from the left ventricle of noninfarcted control mice. Determination of tissues' elastic moduli was carried out by mechanical testing in an atomic force microscope.SDF-1α-treated peri-infarct tissue most closely approximated the elasticity of normal ventricle and was significantly more elastic than saline-treated peri-infarct myocardium (109 ± 22.9 kPa vs 295 ± 42.3 kPa; P < .0001). Myocardial scar, the strength of which depends on matrix deposition from vasculature at the peri-infarct edge, was stiffer in SDF-1α-treated animals than in controls (804 ± 102.2 kPa vs 144 ± 27.5 kPa; P < .0001).Direct quantification of myocardial elastic properties demonstrates the ability of SDF-1α to re-engineer evolving myocardial infarct and peri-infarct tissues. By increasing elasticity of the ischemic and dysfunctional peri-infarct border zone and bolstering the weak, aneurysm-prone scar, SDF-1α therapy may confer a mechanical advantage to resist adverse remodeling after infarction.

    View details for DOI 10.1016/j.jtcvs.2011.12.028

    View details for Web of Science ID 000301609200036

    View details for PubMedID 22264415

  • Feasibility of hybrid thoracoscopic lobectomy and en-bloc chest wall resection(dagger) 19th European Conference on General Thoracic Surgery of the European-Society-of-Thoracic-Surgeons (ESTS) Berry, M. F., Onaitis, M. W., Tong, B. C., Balderson, S. S., Harpole, D. H., D'Amico, T. A. OXFORD UNIV PRESS INC. 2012: 888–92

    Abstract

    Lobectomy with an en-bloc chest wall resection is an effective but potentially morbid treatment of lung cancer invading the chest wall. Minimally invasive approaches to lobectomy have reduced morbidity compared with thoracotomy for early stage lung cancer, but there is insufficient evidence regarding the feasibility of hybrid thoracoscopic lobectomy chest wall resection. We reviewed our experience with an en-bloc chest wall resection and lobectomy to evaluate the outcomes of a hybrid approach using thoracoscopic lobectomy combined with the chest wall resection where rib spreading is avoided.All patients who underwent lobectomy and en-bloc chest wall resection with ribs for primary non-small cell lung cancer from January 2000 to July 2010 were reviewed. Starting in April 2003, a hybrid approach was introduced where thoracoscopic techniques were utilized to accomplish the pulmonary resection and a limited counter incision was used to perform the en-bloc resection of the chest wall, avoiding scapular mobilization and rib spreading. Preoperative, perioperative and outcome variables were assessed using the standard descriptive statistics.During the study period, 105 patients underwent en-bloc lobectomy and chest wall resection, including 93 patients with resection via thoracotomy and 12 patients with resection via the hybrid thoracoscopic approach. Complete resection was achieved in all patients in both groups. Tumour size and the extent of resection were similar in the two groups. There were no conversions and no perioperative mortality in the hybrid group. Post-operative outcomes were similar, although patients who underwent the hybrid approach had a shorter length of stay (P = 0.03).A hybrid approach that combines thoracoscopic lobectomy and chest wall resection is feasible and effective in selected patients. The use of a limited counter incision without rib spreading does not compromise oncologic efficacy. Further experience is needed to determine if this approach provides any advantage in outcomes, including post-operative morbidity.

    View details for DOI 10.1093/ejcts/ezr150

    View details for Web of Science ID 000302021300042

    View details for PubMedID 22219441

  • Perioperative Management of Patients on Clopidogrel (Plavix) Undergoing Major Lung Resection ANNALS OF THORACIC SURGERY Ceppa, D. P., Welsby, I. J., Wang, T. Y., Onaitis, M. W., Tong, B. C., Harpole, D. H., D'Amico, T. A., Berry, M. F. 2011; 92 (6): 1971-1976

    Abstract

    Management of patients requiring antiplatelet therapy with clopidogrel (Plavix) and major lung resection must balance the risks of bleeding and cardiovascular events. We reviewed our experience with patients treated with clopidogrel perioperatively to examine outcomes, including results of a new strategy for high-risk patients.Patients who underwent major lung resection and received perioperative clopidogrel between January 2005 and September 2010 were reviewed. Initially, clopidogrel management consisted of discontinuation approximately 5 days before surgery and resumption immediately after surgery. After July 2010, high-risk patients (drug-eluting coronary stent placement within prior year or previous coronary event after clopidogrel discontinuation) were admitted 2 to 3 days preoperatively and bridged with the intravenous glycoprotein IIb/IIIa receptor inhibitor eptifibatide (Integrilin) according to a multidisciplinary cardiology/anesthesiology/thoracic surgery protocol. Outcomes were compared with control patients (matched for preoperative risk factors and extent of pulmonary resection) who did not receive perioperative clopidogrel.Fifty-four patients who had major lung resection between January 2005 and September 2010 and received clopidogrel perioperatively were matched with 108 control subjects. Both groups had similar mortality, postoperative length of stay, and no differences in the rates of perioperative transfusions, reoperations for bleeding, myocardial infarctions, and strokes. Seven of the 54 clopidogrel patients were admitted preoperatively for an eptifibatide bridge. Two of these patients received perioperative transfusions, but there were no deaths, reoperations, myocardial infarctions, or stroke.Patients taking clopidogrel can safely undergo major lung resection. Treatment with an eptifibatide bridge may minimize the risk of cardiovascular events in higher risk patients.

    View details for DOI 10.1016/j.athoracsur.2011.07.052

    View details for Web of Science ID 000297333300014

    View details for PubMedID 21978871

  • Persistent N2 disease after neoadjuvant chemotherapy for non-small-cell lung cancer 14th World Conference on Lung Cancer Higgins, K. A., Chino, J. P., Ready, N., Onaitis, M. W., Berry, M. F., D'Amico, T. A., Kelsey, C. R. MOSBY-ELSEVIER. 2011: 1175–79

    Abstract

    Patients achieving a mediastinal pathologic complete response with neoadjuvant chemotherapy have improved outcomes compared with patients with persistent N2 disease. How to best manage this latter group of patients is unknown, prompting a review of our institutional experience.All patients who initiated neoadjuvant therapy for non-small-cell lung cancer from 1995 to 2008 were evaluated. The patients were excluded if they had received preoperative radiotherapy, had had a mediastinal pathologic complete response, or had evidence of disease progression after neoadjuvant chemotherapy. The clinical endpoints were calculated using the Kaplan-Meier product-limit method and compared using a log-rank test.A total of 28 patients were identified. The median follow-up period was 24 months. Several neoadjuvant chemotherapy regimens were used, most commonly carboplatin with vinorelbine (36%) or paclitaxel (32%). A partial response to chemotherapy was noted in 23 (82%) and stable disease was noted in 5 (18%) on postchemotherapy imaging. Resection was performed in 22 of 28 patients, consisting of lobectomy in 14, pneumonectomy in 2, and wedge/segmentectomy in 6 (21/22 R0, 1/22 R1). There were no postoperative deaths. Postoperative therapy (radiotherapy and/or additional chemotherapy) was administered to 12 patients (55%). The remaining 6 patients generally received definitive radiotherapy with or without additional chemotherapy. The overall and disease-free survival rate at 1, 3, and 5 years was 75%, 37%, and 37% and 50%, 23%, and 19%, respectively. The survival rate at 5 years was similar between patients undergoing resection (34%) and those receiving definitive radiotherapy with or without chemotherapy (40%; P = .73).Disease-free and overall survival was sufficiently high to warrant aggressive local therapy (surgery or radiotherapy) in patients with persistent N2 disease after neoadjuvant chemotherapy.

    View details for DOI 10.1016/j.jtcvs.2011.07.059

    View details for Web of Science ID 000296337500033

    View details for PubMedID 22014344

  • Incorporating Research into Thoracic Surgery Practice THORACIC SURGERY CLINICS D'Amico, T. A., Tong, B. C., Berry, M. F., Burfeind, W. R., Onaitis, M. W. 2011; 21 (3): 369-?
  • Incorporating research into thoracic surgery practice. Thoracic surgery clinics D'Amico, T. A., Tong, B. C., Berry, M. F., Burfeind, W. R., Onaitis, M. W. 2011; 21 (3): 369-377

    Abstract

    The incorporation of research into a career in thoracic surgery is a complex process. Ideally, the preparation for a career in academic thoracic surgery begins with a research fellowship during training. In the academic setting, a research portfolio might include clinical research, translational research, or basic research. Using strategies for developing collaboration, thoracic surgeons in community-based programs may also be successful clinical investigators. In addition to the rigors of conducting research, strategies for reserving protected time and obtaining grant support must be considered to be successful in academic surgery.

    View details for DOI 10.1016/j.thorsurg.2011.04.004

    View details for PubMedID 21762860

  • INDUCTION CHEMORADIOTHERAPY IS NOT SUPERIOR TO INDUCTION CHEMOTHERAPY ALONE IN PATIENTS WITH STAGE IIIA(N2) NON-SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS Shah, A. A., Berry, M. F., Tzao, C., Rajgor, D., Pietrobon, R., D'Amico, T. A. LIPPINCOTT WILLIAMS & WILKINS. 2011: S1578–S1579
  • A model for morbidity after lung resection in octogenarians 18th European Conference on General Thoracic Surgery of the European-Society-of-Thoracic-Surgeons Berry, M. F., Onaitis, M. W., Tong, B. C., Harpole, D. H., D'Amico, T. A. OXFORD UNIV PRESS INC. 2011: 989–94

    Abstract

    Age is an important risk factor for morbidity after lung resection. This study was performed to identify specific risk factors for complications after lung resection in octogenarians.A prospective database containing patients aged 80 years or older, who underwent lung resection at a single institution between January 2000 and June 2009, was reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed. Morbidity was measured as a patient having any perioperative event as defined by the Society of Thoracic Surgeons General Thoracic Surgery Database. A multivariable risk model for morbidity was developed using a panel of established preoperative and operative variables. Survival was calculated using the Kaplan-Meier method.During the study period, 193 patients aged 80 years or older (median age 82 years) underwent lung resection: wedge resection in 77, segmentectomy in 13, lobectomy in 96, bilobectomy in four, and pneumonectomy in three. Resection was accomplished via thoracoscopy in 149 patients (77%). Operative mortality was 3.6% (seven patients) and morbidity was 46% (89 patients). A total of 181 (94%) patients were discharged directly home. Postoperative events included atrial arrhythmia in 38 patients (20%), prolonged air leak in 24 patients (12%), postoperative transfusion in 22 patients (11%), delirium in 16 patients (8%), need for bronchoscopy in 14 patients (7%), and pneumonia in 10 patients (5%). Significant predictors of morbidity by multivariable analysis included resection greater than wedge (odds ratio 2.98, p=0.006), thoracotomy as operative approach (odds ratio 2.6, p=0.03), and % predicted forced expiratory volume in 1s (odds ratio 1.28 for each 10% decrement, p=0.01).Octogenarians can undergo lung resection with low mortality. Extent of resection, use of a thoracotomy, and impaired lung function increase the risk of complications. Careful evaluation is necessary to select the most appropriate approach in octogenarians being considered for lung resection.

    View details for DOI 10.1016/j.ejcts.2010.09.038

    View details for Web of Science ID 000291586500041

    View details for PubMedID 21276728

  • PERSISTENT N2 DISEASE AFTER NEOADJUVANT CHEMOTHERAPY-NOW WHAT? Higgins, K. A., Ready, N. E., D'Amico, T. A., Onaitis, M. W., Crawford, J., Clough, R., Berry, M. F., Yoo, D., Harpole, D. H., Dunphy, F., Kelsey, C. R. LIPPINCOTT WILLIAMS & WILKINS. 2011: S1572–S1572
  • A comprehensive evaluation for aspiration after esophagectomy reduces the incidence of postoperative pneumonia JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Berry, M. F., Atkins, Z., Tong, B. C., Harpole, D. H., D'Amico, T. A., Onaitis, M. W. 2010; 140 (6): 1266-1271

    Abstract

    This study assesses the effect of using a comprehensive swallowing evaluation before starting oral feedings on aspiration detection and pneumonia occurrence after esophagectomy.The records of all patients undergoing esophagectomy between January 1996 and June 2009 were reviewed. Multivariable logistic regression analysis assessed the effect of preoperative and operative variables on the incidence of aspiration and pneumonia. Separate analyses were performed on patients before (early era, 1996-2002) and after (later era, 2003-2009) a rigorous swallowing evaluation was used routinely before starting oral feedings.During the study period, 799 patients (379 from the early era and 420 from the later era) underwent esophagectomy; 30-day mortality was 3.5% (28 patients). Cervical anastomoses were performed in 76% of patients in the later era compared with 40% of patients in the early era. Overall, 96 (12%) patients had evidence of aspiration postoperatively, and the pneumonia incidence was 14% (113 patients). Age (odds ratio, 1.05 per year; P < .0001) and later era (odds ratio, 1.90; P = .0001) predicted aspiration in all patients in a multivariable model. In the early era, cervical anastomosis and aspiration independently predicted pneumonia. With a comprehensive swallowing evaluation in the later era, the detected incidence of aspiration increased (16% vs 7%, P < .0001), whereas the incidence of pneumonia decreased (11% vs 18%, P = .004) compared with the early era, such that neither anastomotic location nor aspiration predicted pneumonia in the later era.Esophagectomy is often associated with occult aspiration. A comprehensive swallowing evaluation for aspiration before initiating oral feedings significantly decreases the occurrence of pneumonia.

    View details for DOI 10.1016/j.jtcvs.2010.08.038

    View details for Web of Science ID 000284149200010

    View details for PubMedID 20884018

  • Cardiac Angiosarcoma Presenting With Right Coronary Artery Pseudoaneurysm JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Berry, M. F., Williams, M., Welsby, I., Lin, S. 2010; 24 (4): 633-635

    View details for DOI 10.1053/j.jvca.2009.04.002

    View details for Web of Science ID 000280726000016

    View details for PubMedID 19525126

  • Risk Factors for Morbidity After Lobectomy for Lung Cancer in Elderly Patients ANNALS OF THORACIC SURGERY Berry, M. F., Hanna, J., Tong, B. C., Burfeind, W. R., Harpole, D. H., D'Amico, T. A., Onaitis, M. W. 2009; 88 (4): 1093-1099

    Abstract

    Studies evaluating risk factors for complications after lobectomy in elderly patients have not adequately analyzed the effect of using minimally invasive approaches.A model for morbidity including published preoperative risk factors and surgical approach was developed by multivariable logistic regression. All patients aged 70 years or older who underwent lobectomy for primary lung cancer without chest wall resection or airway procedure between December 1999 and October 2007 at a single institution were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Morbidity was measured as a patient having any perioperative complication. The impact of bias in the selection of surgical approach was assessed using propensity scoring.During the study period, 338 patients older than 70 years (mean age, 75.7 +/- 0.2) underwent lobectomy (219 thoracoscopy, 119 thoracotomy). Operative mortality was 3.8% (13 patients) and morbidity was 47% (159 patients). Patients with at least one complication had increased length of stay (8.3 +/- 0.6 versus 3.8 +/- 0.1 days; p < 0.0001) and mortality (6.9% [11 of 159] versus 1.1% [2 of 179]; p = 0.008). Significant predictors of morbidity by multivariable analysis included age (odds ratio, 1.09 per year; p = 0.01) and thoracotomy as surgical approach (odds ratio, 2.21; p = 0.004). Thoracotomy remained a significant predictor of morbidity when the propensity to undergo thoracoscopy was considered (odds ratio, 4.9; p= 0.002).Patients older than 70 years of age can undergo lobectomy for lung cancer with low morbidity and mortality. Advanced age and the use of a thoracotomy increased the risk of complications in this patient population.

    View details for DOI 10.1016/j.athoracsur.2009.06.012

    View details for Web of Science ID 000270388500006

    View details for PubMedID 19766786

  • Giant Thoracic Liposarcoma Treated with Induction Chemotherapy Followed by Surgical Resection JOURNAL OF THORACIC ONCOLOGY Berry, M. F., Sporn, T. A., Moore, J. O., D'Amico, T. A. 2009; 4 (6): 768-769

    View details for Web of Science ID 000266347900017

    View details for PubMedID 19461403

  • Repair of large complex recurrent incisional hernias with retromuscular mesh and panniculectomy AMERICAN JOURNAL OF SURGERY Berry, M. F., Paisley, S., Low, D. W., Rosato, E. F. 2007; 194 (2): 199-204

    Abstract

    Recurrent incisional hernia repair is associated with high recurrence and wound complication rates.The clinical courses of patients who underwent recurrent incisional hernia repair via retromuscular mesh placement with concomitant panniculectomy at a university teaching hospital from 1999 to 2004 were reviewed retrospectively. Postoperative evaluation included a quality of life survey.Forty-seven patients (13 male, 34 female) with an average body mass index of 34.4 kg/m2, an average midline hernia defect of 31.4 cm, and at least 1 and on average 2.5 previous repair attempts underwent hernia repair. Wound infections occurred in 4 patients (8%) and seromas requiring aspiration occurred in 1 patient (2%). Four patients (8%) had re-recurrences of their hernias. All patients rated the postoperative appearance of their abdomen as at least satisfactory.Recurrent incisional hernia repair with a retromuscular mesh and panniculectomy has low recurrence and wound complication rates and excellent patient satisfaction.

    View details for DOI 10.1016/j.amjsurg.2006.10.031

    View details for Web of Science ID 000248110900013

    View details for PubMedID 17618804

  • Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression CELLULAR & MOLECULAR BIOLOGY LETTERS Atluri, P., Morine, K. J., Liao, G. P., Panlilio, C. M., Berry, M. F., Hsu, V. M., Hiesinger, W., Cohen, J. E., Woo, Y. J. 2007; 12 (1): 127-138

    Abstract

    Apelin interacts with the APJ receptor to enhance inotropy. In heart failure, apelin-APJ coupling may provide a means of enhancing myocardial function. The alterations in apelin and APJ receptor concentrations with ischemic cardiomyopathy are poorly understood. We investigated the compensatory changes in endogenous apelin and APJ levels in the setting of ischemic cardiomyopathy.Male, Lewis rats underwent LAD ligation and progressed into heart failure over 6 weeks. Corresponding animals underwent sham thoracotomy as control. Six weeks after initial surgery, the animals underwent hemodynamic functional analysis in the presence of exogenous apelin-13 infusion and the hearts were explanted for western blot and enzyme immunoassay analysis. Western blot analysis of myocardial APJ concentration demonstrated increased APJ receptor protein levels with heart failure (1890750+/-133500 vs. 901600+/-143120 intensity units, n=8, p=0.00001). Total apelin protein levels increased with ischemic heart failure as demonstrated by enzyme immunoassay (12.0+/-4.6 vs. 1.0+/-1.2 ng/ml, n=5, p=0.006) and western blot (1579400+/-477733 vs. 943000+/-157600 intensity units, n=10, p=0.008). Infusion of apelin-13 significantly enhanced myocardial function in sham and failing hearts. We conclude that total myocardial apelin and APJ receptor levels increase in compensation for ischemic cardiomyopathy.

    View details for DOI 10.2478/s11658-006-0058-7

    View details for Web of Science ID 000244632300011

    View details for PubMedID 17119870

  • Complications of thoracoscopic pulmonary resection. Seminars in thoracic and cardiovascular surgery Berry, M. F., D'Amico, T. A. 2007; 19 (4): 350-354

    Abstract

    Thoracoscopic strategies are becoming increasingly utilized in the management of patients with thoracic disease processes, including primary pulmonary malignancy, secondary pulmonary malignancy, granulomatous lung disease, and pleural processes. Although minimally invasive approaches have been demonstrated to improve outcomes and reduce complications, as compared to the conventional approach, the prevention, early recognition, and effective management of complications after thoracoscopic pulmonary resection are still critical factors in optimizing outcomes.

    View details for DOI 10.1053/j.semtcvs.2007.10.001

    View details for PubMedID 18395637

  • Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy JOURNAL OF CARDIAC SURGERY Kolakowski, S., Berry, M. F., Atluri, P., Grand, T., Fisher, O., Moise, A., Cohen, J., Hsu, V., Woo, Y. J. 2006; 21 (6): 559-564

    Abstract

    Heart failure occurs predominantly due to coronary artery disease and may be amenable to novel revascularization therapies. This study evaluated the effects of placental growth factor (PlGF), a potent angiogenic agent, in a rat model of ischemic cardiomyopathy.Wistar rats underwent high proximal ligation of the left anterior descending coronary artery and direct injection of PlGF (n = 10) or saline as a control (n = 10) into the myocardium bordering the ischemic area. After 2 weeks, the following parameters were evaluated: ventricular function with an aortic flow probe and a pressure/volume conductance catheter, left ventricular (LV) geometry by histology, and angiogenesis by immunofluorescence.PlGF animals had increased angiogenesis compared to controls (22.8 +/- 3.5 vs. 12.4 +/- 3.2 endothelial cells/high-powered field, p < 0.03). PlGF animals had less ventricular cavity dilation (LV diameter 8.4 +/- 0.2 vs. 9.2 +/- 0.2 mm, p < 0.03) and increased border zone wall thickness (1.85 +/- 0.1 vs. 1.38 +/- 0.2 mm, p < 0.03). PlGF animals had improved cardiac function as measured by maximum LV pressure (95.7 +/- 4 vs. 73.7 +/- 2 mmHg, p = 0.001), maximum dP/dt (4206 +/- 362 vs. 2978 +/- 236 mmHg/sec, p = 0.007), and ejection fraction (25.7 +/- 2 vs. 18.6 +/- 1%, p = 0.02).Intramyocardial delivery of PlGF following a large myocardial infarction enhanced border zone angiogenesis, attenuated adverse ventricular remodeling, and preserved cardiac function. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.

    View details for DOI 10.1111/j.1540-8191.2006.00296.x

    View details for Web of Science ID 000241625300007

    View details for PubMedID 17073953

  • Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY Berry, M. F., Engler, A. J., Woo, Y. J., Pirolli, T. J., Bish, L. T., Jayasankar, V., Morine, K. J., Gardner, T. J., Discher, D. E., Sweeney, H. L. 2006; 290 (6): H2196-H2203

    Abstract

    Cellular therapy for myocardial injury has improved ventricular function in both animal and clinical studies, though the mechanism of benefit is unclear. This study was undertaken to examine the effects of cellular injection after infarction on myocardial elasticity. Coronary artery ligation of Lewis rats was followed by direct injection of human mesenchymal stem cells (MSCs) into the acutely ischemic myocardium. Two weeks postinfarct, myocardial elasticity was mapped by atomic force microscopy. MSC-injected hearts near the infarct region were twofold stiffer than myocardium from noninfarcted animals but softer than myocardium from vehicle-treated infarcted animals. After 8 wk, the following variables were evaluated: MSC engraftment and left ventricular geometry by histological methods, cardiac function with a pressure-volume conductance catheter, myocardial fibrosis by Masson Trichrome staining, vascularity by immunohistochemistry, and apoptosis by TdT-mediated dUTP nick-end labeling assay. The human cells engrafted and expressed a cardiomyocyte protein but stopped short of full differentiation and did not stimulate significant angiogenesis. MSC-injected hearts showed significantly less fibrosis than controls, as well as less left ventricular dilation, reduced apoptosis, increased myocardial thickness, and preservation of systolic and diastolic cardiac function. In summary, MSC injection after myocardial infarction did not regenerate contracting cardiomyocytes but reduced the stiffness of the subsequent scar and attenuated postinfarction remodeling, preserving some cardiac function. Improving scarred heart muscle compliance could be a functional benefit of cellular cardiomyoplasty.

    View details for DOI 10.1152/ajpheart.01017.2005

    View details for Web of Science ID 000237419600009

    View details for PubMedID 16473959

  • Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy - Invited commentary ANNALS OF THORACIC SURGERY Atluri, P., Liao, G. P., Panlilio, C. M., Hsu, V. M., Leskowitz, M. J., Morine, K. J., Cohen, J. E., Berry, M. F., Suarez, E. E., Murphy, D. A., Lee, W. M., Gardner, T. J., Sweeney, H. L., Woo, Y. J., Dormond, O., Madsen, J. C. 2006; 81 (5): 1728-1737
  • Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy. Annals of thoracic surgery Atluri, P., Liao, G. P., Panlilio, C. M., Hsu, V. M., Leskowitz, M. J., Morine, K. J., Cohen, J. E., Berry, M. F., Suarez, E. E., Murphy, D. A., Lee, W. M., Gardner, T. J., Sweeney, H. L., Woo, Y. J. 2006; 81 (5): 1728-1736

    Abstract

    Ischemic cardiomyopathy is a global health concern with limited therapy. We recently described endogenous revascularization utilizing granulocyte-macrophage colony stimulating factor (GMCSF) to induce endothelial progenitor cell (EPC) production and intramyocardial stromal cell-derived factor-1alpha (SDF) as a specific EPC chemokine. The EPC-mediated neovascularization and enhancement of myocardial function was observed. In this study we examined the regional biologic mechanisms underlying this therapy.Lewis rats underwent left anterior descending coronary artery (LAD) ligation and developed ischemic cardiomyopathy over 6 weeks. Three weeks after ligation, the animals received either subcutaneous GMCSF and intramyocardial SDF injections or saline injections as control. Six weeks after LAD ligation circulating EPC density was studied by flow cytometry. Quadruple immunofluorescent vessel staining for mature, proliferating vasculature was performed. Confocal angiography was utilized to identify fluorescein lectin-lined vessels to assess perfusion. Ischemia reversal was studied by measuring myocardial adenosine triphosphate (ATP) levels. Myocardial viability was assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling detection of apoptosis and quantitation of myofilament density.The GMCSF/SDF therapy enhanced circulating leukocyte (13.1 +/- 4.5 x 10(6) vs 3.1 +/- 0.5 x 10(6)/cc, p = 0.001, n = 6) and EPC (14.2 +/- 6.6 vs 2.2 +/- 2.1/cc, p = 0.001, n = 6) concentrations. Tetraimmunofluorescent labeling demonstrated enhanced stable vasculature with this therapy (39.2 +/- 8.1 vs 25.4 +/- 5.1%, p = 0.006, n = 7). Enhanced perfusion was shown by confocal microangiography of borderzone lectin-labeled vessels (28.2 +/- 5.4 vs 11.5 +/- 3.0 vessels/high power field [hpf], p = 0.00001, n = 10). Ischemia reversal was demonstrated by enhanced cellular ATP levels in the GMCSF/SDF borderzone myocardium (102.5 +/- 31.0 vs 26.9 +/- 4.1 nmol/g, p = 0.008, n = 5). Borderzone cardiomyocyte viability was noted by decreased apoptosis (3.2 +/- 1.4% vs 5.4 +/- 1.0%, p = 0.004, n = 10) and enhanced cardiomyocyte density (40.0 +/- 5.6 vs 27.0 +/- 6 myofilaments/hpf, p = 0.01, n=10).Endogenous revascularization for ischemic cardiomyopathy utilizing GMCSF EPC upregulation and SDF EPC chemokinesis upregulates circulating EPCs, enhances vascular stability, and augments myocardial function by enhancing perfusion, reversing cellular ischemia, and increasing cardiomyocyte viability.

    View details for PubMedID 16631663

  • Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction. Heart, lung & circulation Cohen, J. E., Atluri, P., Taylor, M. D., Grand, T. J., Liao, G. P., Panlilio, C. M., Suarez, E. E., Zentko, S. E., Hsu, V. M., Berry, M. F., Smith, M. J., Gardner, T. J., Sweeney, H. L., Woo, Y. J. 2006; 15 (2): 119-123

    Abstract

    Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia.Male Wistar rats, 250-300 g, underwent 30 min occlusion of the left anterior descending coronary artery followed by 30 min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30 min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5 min of ischemia and assayed for ATP levels.Compared to controls (n=8), FDP animals (n=8) demonstrated significantly improved maximal left ventricular pressure (100.5+/-5.4 mmHg versus 69.1+/-1.9 mmHg; p<0.0005), dP/dt (5296+/-531 mmHg/s versus 2940+/-175 mmHg/s; p<0.0028), ejection fraction (29.1+/-1.7% versus 20.4+/-1.4%; p<0.0017), and preload adjusted maximal power (59.3+/-5.0 mW/microL(2) versus 44.4+/-4.6 mW/microL(2); p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535+/-156 nmol/g ischemic tissue versus 160+/-9.0 nmol/g ischemic tissue; p<0.0369).The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia.

    View details for PubMedID 16469539

  • Neurological monitoring and off-pump surgery in a very high-risk stroke patient ANNALS OF THORACIC SURGERY Berry, M. F., McGarvey, M. L., Zeng, L., Woo, Y. J. 2005; 80 (6): 2372-2374

    Abstract

    Stroke remains a high risk of coronary artery bypass grafting. We present a patient with progressively symptomatic coronary disease and severe four-vessel cerebrovascular disease not amenable to revascularization. This patient underwent coronary revascularization without neurologic complication using off-pump coronary surgery to avoid aortic manipulation and intraoperative electroencephalographic monitoring of cerebral perfusion. This management strategy may reduce the stroke risk in similar patients.

    View details for DOI 10.1016/j.athoracsur.2004.06.064

    View details for Web of Science ID 000233926800070

    View details for PubMedID 16305918

  • Neovasculogenic therapy with granulocyte-monocyte colony stimulating factor and stromal cell derived factor-1 alpha augments perfusion, reverses ischemia and preserves cardiomyocyte viability in ischemic cardiomyopathy 78th Annual Scientific Session of the American-Heart-Association Atluri, P., Liao, G. P., Panlilio, C. M., Morine, K. J., Berry, M. F., Cohen, J. E., Suarez, E. E., Hsu, V., Smith, M. J., Gardner, T. J., Sweeney, H. L., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2005: U503–U503
  • Treatment with granulocyte monocyte colony stimulating factor and stromal cell derived factor-1alpha enhances endothelial progenitor cell mediated myocardial perfusion and viability in ischemic cardiomyopathy 91st Annual Clinical Congress of the American-College-of-Surgeons Atluri, T., Liao, G., Panlilio, C., Morine, K., Berry, M., Hsu, V., Cohen, J., Suarez, E., Smith, M., Sweeney, H. L., Woo, Y. J. ELSEVIER SCIENCE INC. 2005: S44–S44
  • Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Woo, Y. J., Grand, T. J., Berry, M. F., Atluri, P., Moise, M. A., Hsu, V. M., Cohen, J., Fisher, O., Burdick, J., Taylor, M., Zentko, S., Liao, G., Smith, M., Kolakowski, S., Jayasankar, V., Gardner, T. J., Sweeney, H. L. 2005; 130 (2): 321-329

    Abstract

    Ischemic heart failure is an increasingly prevalent global health concern with major morbidity and mortality. Currently, therapies are limited, and novel revascularization methods might have a role. This study examined enhancing endogenous myocardial revascularization by expanding bone marrow-derived endothelial progenitor cells with the marrow stimulant granulocyte-monocyte colony-stimulating factor and recruiting the endothelial progenitor cells with intramyocardial administration of the potent endothelial progenitor cell chemokine stromal cell-derived factor.Ischemic cardiomyopathy was induced in Lewis rats (n = 40) through left anterior descending coronary artery ligation. After 3 weeks, animals were randomized into 4 groups: saline control, granulocyte-monocyte colony-stimulating factor only (GM-CSF only), stromal cell-derived factor only (SDF only), and combined stromal cell-derived factor/granulocyte-monocyte colony-stimulating factor (SDF/GM-CSF) (n = 10 each). After another 3 weeks, hearts were analyzed for endothelial progenitor cell density by endothelial progenitor cell marker colocalization immunohistochemistry, vasculogenesis by von Willebrand immunohistochemistry, ventricular geometry by hematoxylin-and-eosin microscopy, and in vivo myocardial function with an intracavitary pressure-volume conductance microcatheter.The saline control, GM-CSF only, and SDF only groups were equivalent. Compared with the saline control group, animals in the SDF/GM-CSF group exhibited increased endothelial progenitor cell density (21.7 +/- 3.2 vs 9.6 +/- 3.1 CD34 + /vascular endothelial growth factor receptor 2-positive cells per high-power field, P = .01). There was enhanced vascularity (44.1 +/- 5.5 versus 23.8 +/- 2.2 von Willebrand factor-positive vessels per high-power field, P = .007). SDF/GM-CSF group animals experienced less adverse ventricular remodeling, as manifested by less cavitary dilatation (9.8 +/- 0.1 mm vs 10.1 +/- 0.1 mm [control], P = .04) and increased border-zone wall thickness (1.78 +/- 0.19 vs 1.41 +/- 0.16 mm [control], P = .03). (SDF/GM-CSF group animals had improved cardiac function compared with animals in the saline control group (maximum pressure: 93.9 +/- 3.2 vs 71.7 +/- 3.1 mm Hg, P < .001; maximum dP/dt: 3513 +/- 303 vs 2602 +/- 201 mm Hg/s, P < .05; cardiac output: 21.3 +/- 2.7 vs 13.3 +/- 1.3 mL/min, P < .01; end-systolic pressure-volume relationship slope: 1.7 +/- 0.4 vs 0.5 +/- 0.2 mm Hg/microL, P < .01.)This novel revascularization strategy of bone marrow stimulation and intramyocardial delivery of the endothelial progenitor cell chemokine stromal cell-derived factor yielded significantly enhanced myocardial endothelial progenitor cell density, vasculogenesis, geometric preservation, and contractility in a model of ischemic cardiomyopathy.

    View details for DOI 10.1016/j.jtcvs.2004.11.041

    View details for Web of Science ID 000231069700015

    View details for PubMedID 16077394

  • Creatine phosphate administration preserves myocardial function in a model of off-pump coronary revascularization JOURNAL OF CARDIOVASCULAR SURGERY Woo, Y. J., Grand, T. J., Zentko, S., Cohen, J. E., Hsu, V., Atluri, P., Berry, M. F., Taylor, M. D., Moise, M. A., Fisher, O., Kolakowski, S. 2005; 46 (3): 297-303

    Abstract

    Off pump coronary artery bypass grafting (OPCAB) involves, and is occasionally impaired by obligatory regional myocardial ischemia, particularly with the use of proximal coronary in-flow occlusion techniques. Intracoronary shunts do not guarantee absence of distal ischemia given their small inner diameter and the presence of proximal coronary stenosis. Additional adjunctive measures to provide short-term myocardial protection may facilitate OPCAB. High-energy phosphate supplementation with creatine phosphate prior to ischemia may attenuate ischemic dysfunction.In a rodent model of a transient coronary occlusion and myocardial ischemia, 36 animals underwent preischemic intravenous infusion of either creatine phosphate or saline, 10 minutes of proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion. Rats underwent continuous intracavitary pressure monitoring and cellular ATP levels were quantified using a luciferin/luciferase bioluminescence assay.Within 2 minutes of ischemia onset, creatine phosphate animals exhibited statistically significant greater preservation of myocardial function compared to controls, an augmentation which persisted throughout the duration of ischemia and subsequent reperfusion. Furthermore, significantly greater cellular ATP levels were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue, n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014).A strategy of intravenous high-energy phosphate administration successfully prevented ischemic ventricular dysfunction in a rodent model of OPCAB.

    View details for Web of Science ID 000231101300014

    View details for PubMedID 15956929

  • Ischemic heart failure increases local concentrations of the endogenous inotrope apelin-13 and the APJ receptor 27th Annual Meeting of the American Section of the International-Society-of-Heart-Research Atluri, P., Morine, K. J., Liao, G., Panlilio, C., Berry, M. F., Hsu, V., Cohen, J., Smith, M., Suarez, E., Sweeney, H. L., Woo, Y. J. ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. 2005: 850–50
  • Ethyl pyruvate enhances ATP levels, reduces oxidative stress and preserves cardiac function in a rat model of off-pump coronary bypass. Heart, lung & circulation Taylor, M. D., Grand, T. J., Cohen, J. E., Hsu, V., Liao, G. P., Zentko, S., Berry, M. F., Gardner, T. J., Woo, Y. J. 2005; 14 (1): 25-31

    Abstract

    Off-pump coronary artery bypass grafting is associated with transient periods of myocardial ischemia during revascularization resulting in myocardial contractile dysfunction and oxidative injury. The purpose of this study was to investigate the efficacy of ethyl pyruvate as a myocardial protective agent in a rat model of off-pump coronary artery bypass grafting associated with transient myocardial dysfunction without infarction.Wistar rats were subjected to transient ischemia via 10 min occlusion of the LAD coronary artery followed by 10 min of reperfusion. Animals received an IV bolus of Ringer's solution as a control (n=10) or Ringer's ethyl pyruvate (n=10) immediately before the initiation of ischemia and reperfusion. Myocardial ATP and lipid peroxidation levels were quantified for an estimation of energetics and oxidative stress, respectively. In vivo cardiac function was assessed throughout the ischemia and reperfusion periods.Ethyl pyruvate significantly increased myocardial ATP levels compared to controls (2650+/-759 nmol/g versus 892+/-276 nmol/g, p=0.04). Myocardial oxidative stress was significantly reduced in animals treated with ethyl pyruvate compared to controls (70.4+/-2.6 nmol/g versus 81.8+/-2.4 nmol/g, p=0.04). dP/dt max and cardiac output were significantly greater in the ethyl pyruvate group compared to controls during ischemia and reperfusion.Ethyl pyruvate enhances myocardial ATP levels, reduces oxidative stress, and preserves myocardial function in a model of transient ischemia/reperfusion injury not subject to myocardial infarction.

    View details for PubMedID 16352248

  • Induction of angiogenesis and inhibition of apoptosis by hepatocyt growth factor effectively treats postischemic heart failure JOURNAL OF CARDIAC SURGERY Jayasankar, V., Woo, Y. J., Pirolli, T. J., Bish, L. T., Berry, M. F., Burdick, J., Gardner, T. J., Sweeney, H. L. 2005; 20 (1): 93-101

    Abstract

    Heart failure following myocardial infarction (MI) is a significant cause of morbidity and mortality and remains a difficult therapeutic challenge. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI.The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure-volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot.Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 +/- 3 vs. control 64 +/- 5 mmHg, p < 0.05), maximum dP/dt (3024 +/- 266 vs. 1907 +/- 360 mmHg/sec, p < 0.05), maximum dV/dt (133 +/- 20 vs. 84 +/- 6 muL/sec, p < 0.05), and LV border zone wall thickness (1.98 +/- 0.06 vs. 1.53 +/- 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 +/- 10.0 vs. 90 +/- 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 +/- 0.3 vs. 8.2 +/- 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group.Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure.

    View details for Web of Science ID 000226958900019

    View details for PubMedID 15673421

  • Targeted overexpression of leukemia inhibitory factor to preserve myocardium in a rat model of postinfarction heart failure 84th Annual Meeting of the American-Association-for-Thoracic-Surgery Berry, M. F., Pirolli, T. J., Jayasankar, V., Morine, K. J., Moise, M. A., Fisher, O., Gardner, T. J., Patterson, P. H., Woo, Y. J. MOSBY-ELSEVIER. 2004: 866–75

    Abstract

    Myocardial infarction leads to cardiomyocyte loss. The cytokine leukemia inhibitory factor regulates the differentiation and growth of embryonic and adult heart tissue. This study examined the effects of gene transfer of leukemia inhibitory factor in infarcted rat hearts.Lewis rats underwent ligation of the left anterior descending coronary artery and direct injection of adenovirus encoding leukemia inhibitory factor (n = 10) or null transgene as control (n = 10) into the myocardium bordering the ischemic area. A sham operation group (n = 10) underwent thoracotomy without ligation. After 6 weeks, the following parameters were evaluated: cardiac function with a pressure-volume conductance catheter, left ventricular geometry and architecture by histologic methods; myocardial fibrosis by Masson trichrome staining, apoptosis by terminal deoxynucleotidal transferase-mediated deoxyuridine triphosphate nick-end labeling assay, and cardiomyocyte size by immunofluorescence.Rats with overexpression of leukemia inhibitory factor had more preserved myocardium and less fibrosis in both the infarct and its border zone. The border zone in leukemia inhibitory factor-treated animals contained fewer apoptotic nuclei (1.6% +/- 0.1% vs 3.3% +/- 0.2%, P < .05) than that in control animals and demonstrated cardiomyocytes with larger cross-sectional areas (910 +/- 60 microm 2 vs 480 +/- 30 microm 2 , P < .05). Leukemia inhibitory factor-treated animals had increased left ventricular wall thickness (2.1 +/- 0.1 mm vs 1.8 +/- 0.1 mm, P < .05) and less dilation of the left ventricular cavity (237 +/- 22 microL vs 301 +/- 16 microL, P < .05). They also had improved cardiac function, as measured by maximum change in pressure over time (3950 +/- 360 mm Hg/s vs 2750 +/- 230 mm Hg/s, P < .05) and the slopes of the maximum change in pressure over time-end-diastolic volume relationship (68 +/- 5 mm Hg/[s . microL] vs 46 +/- 6 mm Hg/[s . microL], P < .05) and the preload recruitable stroke work relationship (89 +/- 10 mm Hg vs 44 +/- 4 mm Hg, P < .05).Myocardial gene transfer of leukemia inhibitory factor preserved cardiac tissue, geometry, and function after myocardial infarction in rats.

    View details for DOI 10.1016/j.jtcvs.2004.06.046

    View details for Web of Science ID 000225475700012

    View details for PubMedID 15573071

  • Substrate compliance alters human mesenchymal stem cell morphology 44th Annual Meeting of the American-Society-for-Cell-Biology Engler, A. J., Berry, M., Sweeney, H. L., Discher, D. E. AMER SOC CELL BIOLOGY. 2004: 298A–298A
  • Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy 77th Scientific Meeting of the American-Heart-Association Kolakowski, S., Grand, T., Fisher, O., Berry, M., Moise, M. A., Cohen, J., Hsu, V., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2004: 398–98
  • Inhibition of matrix metalloproteinase activity by TIMP-1 gene transfer effectively treats ischemic cardiomyopathy CIRCULATION Jayasankar, V., Woo, Y. J., Bish, L. T., Pirolli, T. J., Berry, M. F., Burdick, J., Bhalla, R. C., Sharma, R. V., Gardner, T. J., Sweeney, H. L. 2004; 110 (11): II180-II186

    Abstract

    Enhanced activity of matrix metalloproteinases (MMPs) has been associated with extracellular matrix degradation and ischemic heart failure in animal models and human patients. This study evaluated the effects of MMP inhibition by gene transfer of TIMP-1 in a rat model of ischemic cardiomyopathy.Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient adenovirus encoding TIMP-1 (n=8) or null virus as control vector (n=8), and animals were analyzed after 6 weeks. Both systolic and diastolic cardiac function was significantly preserved in the TIMP-1 group compared with control animals (maximum left ventricular [LV] pressure: TIMP-1 70+/-10 versus control 56+/-12 mmHg, P<0.05; maximum dP/dt 2697+/-842 versus 1622+/-527 mmHg/sec, P<0.01; minimum dP/dt -2900+/-917 versus -1195+/-593, P<0.001). Ventricular geometry was significantly preserved in the TIMP-1 group (LV diameter 13.0+/-0.7 versus control 14.4+/-0.4 mm, P<0.001; border-zone wall thickness 1.59+/-0.11 versus control 1.28+/-0.19 mm, P<0.05), and this was associated with a reduction in myocardial fibrosis (2.36+/-0.87 versus control 3.89+/-1.79 microg hydroxyproline/mg tissue, P<0.05). MMP activity was reduced in the TIMP-1 animals (1.5+/-0.9 versus control 43.1+/-14.9 ng of MMP-1 activity, P<0.05).TIMP-1 gene transfer inhibits MMP activity and preserves cardiac function and geometry in ischemic cardiomyopathy. The reduction in myocardial fibrosis may be primarily responsible for the improved diastolic function in treated animals. TIMP-1 overexpression is a promising therapeutic target for continued investigation.

    View details for DOI 10.1161/01.CIR.0000138946.29375.49

    View details for Web of Science ID 000224023600032

    View details for PubMedID 15364860

  • Apelin has in vivo inotropic effects on normal and failing hearts CIRCULATION Berry, M. F., Pirolli, T. J., Jayasankar, V., Burdick, J., Morine, K. J., Gardner, T. J., Woo, Y. J. 2004; 110 (11): II187-II193

    Abstract

    Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat hearts using a novel combination of a perivascular flow probe and a conductance catheter.Native rats (n =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 microg/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 mm Hg for native animals).The present study is the first to show that apelin has positive inotropic effects in vivo in both normal rat hearts and rat hearts in failure after myocardial infarction. Apelin may have use as an acute inotropic agent in patients with ischemic heart failure.

    View details for DOI 10.1161/01.CIR.0000138382.57325.5c

    View details for Web of Science ID 000224023600033

    View details for PubMedID 15364861

  • Administration of a tumor necrosis factor inhibitor at the time of myocardial infarction attenuates subsequent ventricular remodeling JOURNAL OF HEART AND LUNG TRANSPLANTATION Berry, M. F., Woo, Y. J., Pirolli, T. J., Bish, L. T., Moise, M. A., Burdick, J. W., Morine, K. J., Jayasankar, V., Gardner, T. J., Sweeney, H. L. 2004; 23 (9): 1061-1068

    Abstract

    Tumor necrosis factor (TNF) causes myocardial extracellular matrix remodeling and fibrosis in myocardial infarction and chronic heart failure models. Pre-clinical and clinical trials of TNF inhibition in chronic heart failure have shown conflicting results. This study examined the effects of the administration of a TNF inhibitor immediately after myocardial infarction on the development of heart failure.Lewis rats underwent coronary artery ligation and then received either intravenous etanercept (n = 14), a soluble dimerized TNF receptor that inhibits TNF, or saline as control (n = 13). Leukocyte infiltration into the infarct borderzone was evaluated 4 days post-ligation in 7 animals (etanercept = 4, control = 3). After 6 weeks, the following parameters were evaluated in the remaining animals: cardiac function with a pressure-volume conductance catheter, left ventricular (LV) geometry, and borderzone collagenase activity.Etanercept rats had significantly less borderzone leukocyte infiltration 4 days post-infarction than controls (10.7 +/- 0.5 vs 18.0, +/-2.0 cells/high power field; p < 0.05). At 6 weeks, TNF inhibition resulted in significantly reduced borderzone collagenase activity (110 +/- 30 vs 470 +/- 140 activity units; p < 0.05) and increased LV wall thickness (2.1 +/- 0.1 vs 1.8 +/- 0.1 mm, p < 0.05). Etanercept rats had better systolic function as measured by maximum LV pressure (84 +/- 3 mm Hg vs 68 +/- 5 mm Hg, p < 0.05) and the maximum change in left ventricular pressure over time (maximum dP/dt) (3,110 +/- 230 vs 2,260 +/- 190 mm Hg/sec, p < 0.05), and better diastolic function as measured by minimum dP/dt (-3,060 +/- 240 vs -1,860 +/- 230 mm Hg/sec; p < 0.05) and the relaxation time constant (14.6 +/- 0.6 vs 17.9 +/- 1.2 msec; p < 0.05).TNF inhibition after infarction reduced leukocyte infiltration and extracellular matrix turnover and preserved cardiac function.

    View details for DOI 10.1016/j.healun.2004.06.021

    View details for Web of Science ID 000224230300007

    View details for PubMedID 15454172

  • GMCSF and SDF treatment induces neovasculogenesis in a mouse ischemic hindlimb model 90th Annual Clinical Congress of the American-College-of-Surgeons Moise, M. A., Berry, M., Grand, T., Fisher, O., Morris, L., Kolakowski, S., Hsu, V., Cohen, J., Sweeney, H. L., Woo, Y. J. ELSEVIER SCIENCE INC. 2004: S105–S105
  • Local myocardial overexpression of growth hormone attenuates postinfarction remodeling and preserves cardiac function ANNALS OF THORACIC SURGERY Jayasankar, V., Bish, L. T., Pirolli, T. J., Berry, M. F., Burdick, J., Woo, Y. J. 2004; 77 (6): 2122-2129

    Abstract

    Ventricular remodeling with chamber dilation and wall thinning is seen in postinfarction heart failure. Growth hormone induces myocardial hypertrophy when oversecreted. We hypothesized that localized myocardial hypertrophy induced by gene transfer of growth hormone could inhibit remodeling and preserve cardiac function after myocardial infarction.Rats underwent direct intramyocardial injection of adenovirus encoding either human growth hormone (n = 9) or empty null vector as control (n = 9) 3 weeks after ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after delivery: hemodynamics, ventricular geometry, cardiomyocyte fiber size, and serum growth hormone levels.The growth hormone group had significantly better systolic cardiac function as measured by maximum left ventricular pressure (73.6 +/- 6.9 mm Hg versus control 63.7 +/- 7.8 mm Hg, p < 0.05) and maximum dP/dt (2845 +/- 453 mm Hg/s versus 1949 +/- 605 mm Hg/s, p < 0.005), and diastolic function as measured by minimum dP/dt (-2520 +/- 402 mm Hg/s versus -1500 +/- 774 mm Hg/s, p < 0.01). Ventricular geometry was preserved in the growth hormone group (ventricular diameter 12.2 +/- 0.7 mm versus control 13.1 +/- 0.4 mm, p < 0.05; borderzone wall thickness 2.0 +/- 0.2 mm versus 1.5 +/- 0.1 mm, p < 0.001), and was associated with cardiomyocyte hypertrophy (6.09 +/- 0.63 microm versus 4.66 +/- 0.55 microm, p < 0.005). Local myocardial expression of growth hormone was confirmed, whereas serum levels were undetectable after 3 weeks.Local myocardial overexpression of growth hormone after myocardial infarction resulted in cardiomyocyte hypertrophy, attenuated ventricular remodeling, and improved systolic and diastolic cardiac function. The induction of localized myocardial hypertrophy presents a novel therapeutic approach for the treatment of ischemic heart failure.

    View details for DOI 10.1016/j.athoracsur.2003.12.043

    View details for Web of Science ID 000221717200039

    View details for PubMedID 15172279

  • Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia 83rd Annual Meeting of the American-Association-for-Thoracic-Surgery Woo, Y. J., Taylor, M. D., Cohen, J. E., Jayasankar, V., Bish, L. T., Burdick, J., Pirolli, T. J., Berry, M. F., Hsu, V., Grand, T. MOSBY-ELSEVIER. 2004: 1262–69

    Abstract

    Myocardial injury and dysfunction following ischemia are mediated in part by reactive oxygen species. Pyruvate, a key glycolytic intermediary, is an effective free radical scavenger but unfortunately is limited by aqueous instability. The ester derivative, ethyl pyruvate, is stable in solution and should function as an antioxidant and energy precursor. This study sought to evaluate ethyl pyruvate as a myocardial protective agent in a rat model of ischemia-reperfusion injury.Rats underwent 30-minute ischemia and 30-minute reperfusion of the left anterior descending coronary artery territory. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of either ethyl pyruvate (n = 26) or vehicle control (n = 26). Myocardial high-energy phosphate levels were determined by adenosine triphosphate assay, oxidative injury was measured by lipid peroxidation assay, infarct size was quantified by triphenyltetrazolium chloride staining, and cardiac function was assessed in vivo.Ethyl pyruvate administration significantly increased myocardial adenosine triphosphate levels compared with control (87.6 +/- 29.2 nmol/g vs 10.0 +/- 2.4 nmol/g, P =.03). In ischemic myocardium, ethyl pyruvate reduced oxidative injury compared with control (63.8 +/- 3.3 nmol/g vs 89.5 +/- 3.0 nmol/g, P <.001). Ethyl pyruvate diminished infarct size as a percentage of area at risk (25.3% +/- 1.5% vs 33.6% +/- 2.1%, P =.005). Ethyl pyruvate improved myocardial function compared with control (maximum pressure: 86.6 +/- 2.9 mm Hg vs 73.5 +/- 2.5 mm Hg, P <.001; maximum rate of pressure rise: 3518 +/- 243 mm Hg/s vs 2703 +/- 175 mm Hg/s, P =.005; maximal rate of ventricular systolic volume ejection: 3097 +/- 479 microL/s vs 2120 +/- 287 microL/s, P =.04; ejection fraction: 41.9% +/- 3.8% vs 31.4% +/- 4.1%, P =.03; cardiac output: 26.7 +/- 0.9 mL/min vs 22.7 +/- 1.3 mL/min, P =.01; and end-systolic pressure-volume relationship slope: 1.09 +/- 0.22 vs 0.59 +/- 0.2, P =.02).In this study of myocardial ischemia-reperfusion injury, ethyl pyruvate enhanced myocardial adenosine triphosphate levels, attenuated myocardial oxidative injury, decreased infarct size, and preserved cardiac function.

    View details for DOI 10.1016/j.jtcvs.2003.11.032

    View details for Web of Science ID 000221134600006

    View details for PubMedID 15115981

  • Targeted overexpression of growth hormone by adenoviral gene transfer preserves myocardial function and ventricular geometry in ischemic cardiomyopathy JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY Jayasankar, V., Pirolli, T. J., Bish, L. T., Berry, M. F., Burdick, J., Grand, T., Woo, Y. J. 2004; 36 (4): 531-538

    Abstract

    Post-infarction heart failure is characterized by progressive left ventricular dilatation and wall thinning, with both systolic and diastolic cardiac dysfunction. Human growth hormone (GH) stimulates cardiac hypertrophy when secreted in excess and directly enhances cardiomyocyte contractile function. We hypothesized that local myocardial overexpression of GH could prevent ventricular remodeling and heart failure following myocardial infarction (MI) in rats.Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of adenovirus encoding human GH (n = 8) or null virus as control (n = 8). Six weeks following MI, Adeno-GH treated animals had significant preservation of both systolic and diastolic cardiac function compared to Null animals (maximum dP/dt GH 2927 +/- 83 vs Null 1622 +/- 159 mmHg/sec, p < 0.001; minimum dP/dt -2409 +/- 82 vs -1195 +/- 179 mmHg/sec, p < 0.01). GH animals had improved ventricular geometry with decreased chamber dilatation (13.2 +/- 0.13 vs 14.4+/-0.15 mm, p < 0.001) and increased wall thickness (2.02 +/- 0.10 vs 1.28 +/- 0.07 mm, p < 0.001), and this was associated with advantageous myocardial hypertrophy with increased cardiomyocyte fiber size. Local myocardial overexpression of GH protein was seen in Adeno-GH animals, while serum levels of human GH were undetectable after 6 weeks.Treatment with Adeno-GH following MI resulted in reduced ventricular dilatation, increased local myocardial hypertrophy, and preservation of both systolic and diastolic cardiac function. No significant systemic exposure to growth hormone transgene was observed. The induction of regional hypertrophy is a novel approach to treating heart failure, and may be useful to treat or prevent post-infarction ischemic cardiomyopathy.

    View details for DOI 10.1016/j.yjmcc.2004.01.010

    View details for Web of Science ID 000221181400008

    View details for PubMedID 15081312

  • Repair of acute type A aortic dissection associated with temporal arteritis ANNALS OF THORACIC SURGERY Berry, M. F., Woo, Y. J. 2003; 76 (5): 1717-1718

    Abstract

    The most common predisposing factor for aortic dissection is hypertension. Dissection is also seen in primary aortic diseases, including those that involve aortic inflammation. We report a case of successful repair of an acute type A aortic dissection in a patient with a history of temporal arteritis and pathologic evidence of giant cell aortitis. The literature concerning the association of aortic dissection and temporal arteritis is reviewed.

    View details for DOI 10.1016/S0003-4975(03)00695-7

    View details for Web of Science ID 000186358600081

    View details for PubMedID 14602321

  • Apelin has in vivo inotropic effects on normal and failing hearts 76th Annual Scientific Session of the American-Heart-Association Berry, M. F., Jayasankar, V., Pirolli, T. J., Burdick, J. W., Morine, K. J., Gardner, T. J., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2003: 550–50
  • Ethyl pyruvate reduces free radical production and preserves cardiac function in a rat model of off-pump coronary bypass 76th Annual Scientific Session of the American-Heart-Association Taylor, M. D., Grand, T. J., Cohen, J. E., Hsu, V., Zentko, S., Berry, M. F., Woo, J. LIPPINCOTT WILLIAMS & WILKINS. 2003: 549–49
  • Matrix metalloproteinase inhibition by gene transfer of TIMP-1 attenuates ventricular remodeling and preserves cardiac function in ischemic cardiomyopathy 76th Annual Scientific Session of the American-Heart-Association Jayasankar, V., Bish, L. T., Pirolli, T. J., Berry, M. F., Burdick, J., Bhalla, R. C., Sharma, R. V., Gardner, T. J., Sweeney, H. L., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2003: P-P
  • Mesenchymal stem cell injection into acutely infarcted myocardium decreases fibrosis and apoptosis and significantly preserves ventricular function and geometry 76th Annual Scientific Session of the American-Heart-Association Berry, M. F., Jayasankar, V., Pirolli, T. J., Gardner, T. J., Sweeney, H. L., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2003: 622–22
  • Stromal cell derived factor provides a novel angiogenic therapy for ischemic cardiomyopathy 76th Annual Scientific Session of the American-Heart-Association Woo, Y. J., Grand, T. J., Berry, M., Cohen, J., Hsu, V., Taylor, M., Zentko, S., Burdick, J., Pirolli, T., Jayasankar, V. LIPPINCOTT WILLIAMS & WILKINS. 2003: 621–22
  • Matrix metalloproteinase inhibition by gene transfer of TIMP-1 attenuates ventricular remodeling and preserves cardiac function in ischemic cardiomyopathy 76th Annual Scientific Session of the American-Heart-Association Jayasankar, V., Bish, L. T., Pirolli, T. J., Berry, M. F., Burdick, J., Bhalla, R. C., Sharma, R. V., Gardner, T. J., Sweeney, H. L., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2003: 366–66
  • Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure CIRCULATION Jayasankar, V., Woo, Y. J., Bish, L. T., Pirolli, T. J., Chatterjee, S., Berry, M. F., Burdick, J., Gardner, T. J., Sweeney, H. L. 2003; 108 (10): 230-236
  • Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure. Circulation Jayasankar, V., Woo, Y. J., Bish, L. T., Pirolli, T. J., Chatterjee, S., Berry, M. F., Burdick, J., Gardner, T. J., Sweeney, H. L. 2003; 108: II230-6

    Abstract

    Despite advances in surgical and percutaneous coronary revascularization, ongoing ischemia that is not amenable to standard revascularization techniques is a major cause of morbidity and mortality. Hepatocyte Growth Factor (HGF) has potent angiogenic and anti-apoptotic activities, and this study evaluated the functional and biochemical effects of HGF gene transfer in a rat model of postinfarction heart failure.Lewis rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient recombinant adenovirus encoding HGF (n=10) or empty null virus as control (n=9), and animals were analyzed after six weeks. Pressure-volume conductance catheter measurements demonstrated significantly preserved contractile function in the HGF group compared with Null control animals as measured by maximum developed LV pressure (79+/-5 versus 56+/-4 mm Hg, P<0.001) and maximum dP/dt (2890+/-326 versus 1622+/-159 mm Hg/sec, P<0.01). Significant preservation of LV geometry was associated with HGF treatment (LV Diameter HGF 13.1+/-0.54 versus Null 14.4+/-0.15 mm P<0.01; LV wall thickness 1.73+/-0.10 versus 1.28+/-0.07 mm P<0.01). Angiogenesis was significantly enhanced in HGF treated animals as measured by both Von Willebrand's Factor immunohistochemical staining and a microsphere assay. TUNEL analysis revealed a significant reduction in apoptosis in the HGF group (3.42+/-0.83% versus 8.36+/-1.16%, P<0.01), which correlated with increased Bcl-2 and Bcl-xL expression in the HGF animals.Hepatocyte Growth Factor gene transfer following a large myocardial infarction results in significantly preserved myocardial function and geometry, and is associated with significant angiogenesis and a reduction in apoptosis. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.

    View details for PubMedID 12970238

  • Local myocardial growth hormone overexpression limits left ventricular dysfunction and remodeling in experimental heart failure 89th Annual Clinical Congress of the American-College-of-Surgeons Jayasankar, V., Berry, M., Bish, L., Pirolli, T., Burdick, J., Gardner, T., Woo, Y. J. ELSEVIER SCIENCE INC. 2003: S26–S27
  • Hepatocyte growth factor treatment preserves post-infarction cardiac function Asia Pacific Scientific Forum on New Discoveries in Cardiovascular Disease and Stroke Jayasankar, V., Berry, M. F., Chatterjee, S., Bish, L. T., Pirolli, T. J., Gardner, T. J., Sweeney, H. L., Woo, Y. J. LIPPINCOTT WILLIAMS & WILKINS. 2003: E139–E139
  • Treatment of experimental heart failure with hepatocyte growth factor 52nd Annual Scientific Session of the American-College-of-Cardiology Jayasankar, V., Pirolli, T. J., Bish, L. T., Berry, M. F., Woo, J., Sweeney, H. L., Gardner, T. J. ELSEVIER SCIENCE INC. 2003: 544A–544A
  • Dexon mesh splenorrhaphy for intraoperative splenic injuries AMERICAN SURGEON Berry, M. F., Rosato, E. F., Williams, N. N. 2003; 69 (2): 176-180

    Abstract

    The preferred management option for intraoperative splenic injuries is organ repair and preservation rather than splenectomy given the important immunologic function of the spleen. Wrapping the injured spleen with a Dexon mesh has been shown to be an effective alternative to splenectomy for significant splenic bleeding. However, this technique uses a foreign body that carries a theoretical infectious risk particularly in cases in which the alimentary tract has been opened. This study was undertaken to evaluate whether Dexon mesh splenorrhaphy when used for intraoperative splenic injuries was associated with significant infectious complications. The clinical courses of 23 patients who had Dexon mesh splenorrhaphy performed at a university teaching hospital for intraoperative splenic injury from 1991 to 1999 were reviewed. Eleven patients (48%) had their gastrointestinal tract opened during the surgery. No patients developed an intra-abdominal abscess or required reoperation for bleeding. The most common postoperative complications were left lower lobe atelectasis (18 patients, 78%), postoperative fever (13 patients, 56%), and left pleural effusion (12 patients, 52%). Dexon mesh splenorrhaphy effectively controls splenic bleeding due to intraoperative injury without significant infectious complications.

    View details for Web of Science ID 000181435900022

    View details for PubMedID 12641363

  • Outcome of pancreaticoduodenectomy and impact of adjuvant therapy for ampullary carcinomas 41st Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO 99) Lee, J. H., Whittington, R., Williams, N. N., Berry, M. F., Vaughn, D. J., Haller, D. G., Rosato, E. F. ELSEVIER SCIENCE INC. 2000: 945–53

    Abstract

    To determine the clinical outcomes and potential impact of adjuvant chemoradiation in patients undergoing surgical resection of ampullary carcinoma.Between 1988 and 1997, 39 patients underwent pancreaticoduodenectomy for ampullary adenocarcinomas. Clinical and pathologic factors, adjuvant therapy records, and disease status were obtained from chart review. Thirteen (33%) patients received adjuvant chemoradiation. Radiation therapy was delivered to the surgical bed and regional nodes to a median dose of 4,860 cGy with concurrent bolus or continuous infusion of 5-fluorouracil. Outcomes measures included locoregional control, disease-free survival, and overall survival. Univariate analysis was used to assess the impact of various patient- and tumor-related factors and the use of adjuvant therapy. Twenty (51%) patients with tumor invasion into the pancreas (T3) or node-positive disease were classified in a "high-risk" subgroup.After a median follow-up of 45 months for survivors, overall 3-year survival was 55%. Survival was significantly worse for patients with positive nodes (23% vs. 73%, p < 0.001) and high-risk status (30% vs. 80%, p = 0.002). Disease-free survival was 54% at 3 years. There were 3 postoperative deaths, and these patients (all high risk) are excluded from further analysis on adjuvant therapy. In univariate analysis, the use of adjuvant chemoradiation had no clear impact on local-regional control or overall survival. However, by controlling for risk status in multivariate analysis, the use of adjuvant therapy reached statistical significance for overall survival (p = 0. 03). Among the high-risk patients, 7 (77%) of 9 patients receiving adjuvant therapy remained disease-free during follow-up compared with only 1 (14%) of 7 patients not receiving adjuvant therapy (p = 0.012).Despite the relatively favorable prognosis of ampullary carcinomas compared with other pancreaticobiliary tumors, patients with nodal metastases or T3 disease are at high risk for disease relapse. The use of adjuvant chemoradiation may improve long-term disease control in these patients.

    View details for Web of Science ID 000087845500013

    View details for PubMedID 10863064

  • Surgical management of pancreatic neuroendocrine tumors. Berry, M. F., Williams, N. N., Lee, J. H., Whittington, R., Canter, R. J., Rosato, E. F. W B SAUNDERS CO-ELSEVIER INC. 2000: A1504–A1505