Mark Berry, MD

All Publications

• 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

• 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

  View details for DOI 10.1053/j.jvca.2016.04.029

  View details for Web of Science ID 000400794400035

• 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 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

• 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

• 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

• 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 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

• 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

• 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

• 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

• 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

• 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

• 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

  View details for DOI 10.1016/j.cllc.2015.07.005

  View details for Web of Science ID 000367538900007

• 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

  View details for DOI 10.1016/j.lungcan.2015.10.011

  View details for Web of Science ID 000366873700027

• 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

  View details for DOI 10.1016/j.jtcvs.2015.06.062

  View details for Web of Science ID 000365040700034

  View details for PubMedID 26259994

• 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

• 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

  View details for DOI 10.1111/dote.12285

  View details for Web of Science ID 000368332300011

• 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

  View details for DOI 10.1016/j.athoracsur.2015.02.076

  View details for Web of Science ID 000358796800050

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

  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

  View details for DOI 10.1097/JTO.0000000000000384

  View details for Web of Science ID 000346986500024

• Use of Amiodarone After Major Lung Resection 60th Annual Meeting of the Southern-Thoracic-Surgical-Association Berry, M. F., D'Amico, T. A., Onaitis, M. W. ELSEVIER SCIENCE INC. 2014: 1199–1206

  View details for DOI 10.1016/j.athoracsur.2014.05.038

  View details for Web of Science ID 000343143400016

• 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

  View details for DOI 10.1016/j.athoracsur.2014.05.068

  View details for Web of Science ID 000343143400017

• 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

• 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

• 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

• 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

• 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

  View details for Web of Science ID 000333866700148

• 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

  View details for Web of Science ID 000329155900088

• 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

• 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

• 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

  View details for Web of Science ID 000326375700081

• 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

• 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

  View details for DOI 10.1111/j.1759-7714.2012.00162.x

  View details for Web of Science ID 000318102200006

• Does Pneumonectomy Have a Role in the Treatment of Stage IIIA Non-Small Cell Lung Cancer? 59th Annual Meeting of the Southern-Thoracic-Surgical-Association (STSA) Shah, A. A., Worni, M., Kelsey, C. R., Onaitis, M. W., D'Amico, T. A., Berry, M. F. ELSEVIER SCIENCE INC. 2013: 1700–1707

  Abstract

  The role of surgical resection for stage IIIA non-small cell lung cancer (NSCLC) is unclear. We sought to examine outcomes after pneumonectomy for patients with stage IIIA disease.All patients with stage IIIA NSCLC who had pneumonectomy at a single institution between 1999 and 2010 were reviewed. The Kaplan-Meier method was used to estimate long-term survival and multivariable Cox proportional hazards regression was used to identify clinical characteristics associated with survival.During the study period, 324 patients had surgical resection of stage IIIA NSCLC. Pneumonectomy was performed in 55 patients, 23 (42%) of whom had N2 disease. Induction treatment was used in 17 patients (31%) overall and in 11 of the patients (48%) with N2 disease. Perioperative mortality was 9% (n = 5) overall and 18% (n = 3) in patients that had received induction therapy (p = 0.17). Complications occurred in 32 patients (58%). Three-year survival was 36% and 5-year survival was 29% for all patients. Three-year survival was 40% for N0-1 patients and 29% for N2 patients (p = 0.59). In multivariable analysis, age over 60 years (hazard ratio [HR] 3.65, p = 0.001), renal insufficiency (HR 5.80, p = 0.007), and induction therapy (HR 2.17, p = 0.05) predicted worse survival, and adjuvant therapy (HR 0.35, p = 0.007) predicted improved survival.Long-term survival after pneumonectomy for stage IIIA NSCLC is within an acceptable range, but pneumonectomy may not be appropriate after induction therapy or in patients with renal insufficiency. Patient selection and operative technique that limit perioperative morbidity and facilitate the use of adjuvant chemotherapy are critical to optimizing outcomes.

  View details for Web of Science ID 000318969500049

  View details for PubMedID 23545195

• 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

• Impact of T status and N status on perioperative outcomes after thoracoscopic lobectomy for lung cancer 38th Annual Meeting of the Western-Thoracic-Surgical-Association Villamizar, N. R., Darrabie, M., Hanna, J., Onaitis, M. W., Tong, B. C., D'Amico, T. A., Berry, M. F. MOSBY-ELSEVIER. 2013: 514–21

  Abstract

  We sought to evaluate the effect of tumor size, location, and clinical nodal status on outcomes after thoracoscopic lobectomy for lung cancer.All patients who underwent attempted thoracoscopic lobectomy for lung cancer between June 1999 and October 2010 at a single institution were reviewed. A model for morbidity including published risk factors as well as tumor size, location, and clinical N status was developed by multivariable logistic regression.During the study period, 916 thoracoscopic lobectomies met study criteria: 329 for peripheral, clinical N0 tumors ≤ 3 cm and 504 for tumors that were central, clinical node positive, or >3 cm. Tumor location could not be documented for 83 patients. Conversions to thoracotomy occurred in 36 patients (4%); patients with clinically node-positive disease had higher conversion rates (11 conversions in 153 clinical N1 to N3 patients [7.2%] vs 25 in 763 clinical N0 patients [3.3%, P = .03]. Overall operative mortality was 1.6% (14 patients) and morbidity was 32% (296 patients). Although patients with larger tumors (P = .006) and central tumors (P = .01) had increased complications by univariate analysis, tumor size >3 cm (P = .17) and central location (P = .5) did not predict significantly overall morbidity in multivariate analysis. Clinical node status did not predict increased complications by univariate or multivariate analysis. Significant predictors of morbidity in multivariable analysis were increasing age, decreasing forced expiratory volume in 1 second, prior chemotherapy, and congestive heart failure.Thoracoscopic lobectomy for lung cancers that are central, clinically node positive, or >3 cm does not confer increased morbidity compared with peripheral, clinical N0 cancers that are <3 cm.

  View details for DOI 10.1016/j.jtcvs.2012.10.039

  View details for Web of Science ID 000313634700035

  View details for PubMedID 23177123

• 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

  View details for Web of Science ID 000303994600028

• 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

  View details for Web of Science ID 000318009804641

• 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

• 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

• Outcomes After Surgical Management of Synchronous Bilateral Primary Lung Cancers Basic Science Forum of the 58th Annual Meeting of the Southern-Thoracic-Surgical-Association Shah, A. A., Barfield, M. E., Kelsey, C. R., Onaitis, M. W., Tong, B., Harpole, D., D'Amico, T. A., Berry, M. F. ELSEVIER SCIENCE INC. 2012: 1055–60

  Abstract

  Distinguishing between synchronous primary lung cancers and metastatic disease in patients with bilateral lung masses is often difficult. The objective of this study is to examine outcomes associated with a strategy of performing staged bilateral resections in patients without N2 disease based on invasive mediastinal staging and without distant metastases.Patients undergoing resections of bilateral synchronous primary lung cancer at our institution between 1997 and 2010 were reviewed. Perioperative complications were graded according to National Cancer Institute guidelines. Survival was estimated using the Kaplan-Meier method and compared using a log-rank test. End points included overall survival, disease-free survival, operative death, cancer recurrence, and postoperative complications.Resections of bilateral synchronous primary lung cancers were performed in 47 patients. Forty-five patients (96%) had at least a unilateral thoracoscopic approach; 28 (60%) had bilateral thoracoscopic approaches. The median postresection length of stay was 3 days. Thirteen patients (28%) had a postoperative complication; only 3 (6%) were grade 3 or higher. There was 1 perioperative death (2%). Eleven patients received adjuvant therapy; only 3 patients in whom adjuvant therapy was indicated did not receive the recommended treatment. The overall 3-year survival was 35%. Survival of patients whose bilateral tumors had identical histology did not differ from patients whose histology was different (p = 0.57). Three-year disease-free survival was 24%.Aggressive surgical treatment of apparent synchronous bilateral primary lung cancer can be performed with low morbidity. Most patients tolerate the bilateral surgeries and adjuvant therapy. Overall survival is sufficiently high to support this aggressive approach.

  View details for DOI 10.1016/j.athoracsur.2011.12.070

  View details for Web of Science ID 000302120200017

  View details for PubMedID 22381451

• 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-?

  View details for DOI 10.1016/j.thorsurg.2011.04.004

  View details for Web of Science ID 000311863400007

• 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

  View details for Web of Science ID 000291769802167

• 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

  View details for Web of Science ID 000291769802158

• 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

• Pulmonary Function Tests Do Not Predict Pulmonary Complications After Thoracoscopic Lobectomy 56th Annual Meeting of the Southern-Thoracic-Surgical-Association Berry, M. F., Villamizar-Ortiz, N. R., Tong, B. C., Burfeind, W. R., Harpole, D. H., D'Amico, T. A., Onaitis, M. W. ELSEVIER SCIENCE INC. 2010: 1044–52

  Abstract

  Pulmonary function tests predict respiratory complications and mortality after lung resection through thoracotomy. We sought to determine the impact of pulmonary function tests upon complications after thoracoscopic lobectomy.A model for morbidity, including published preoperative risk factors and surgical approach, was developed by multivariable logistic regression. All patients who underwent lobectomy for primary lung cancer between December 1999 and October 2007 with preoperative forced expiratory volume in 1 second (FEV1) or diffusion capacity to carbon monoxide (Dlco) 60% or less predicted were reviewed. Preoperative, histopathologic, perioperative, and outcome variables were assessed using standard descriptive statistics. Pulmonary complications were defined as atelectasis requiring bronchoscopy, pneumonia, reintubation, and tracheostomy.During the study period, 340 patients (median age 67) with Dlco or FEV1 60% or less (mean % predicted FEV1, 55+/-1; mean % predicted Dlco, 61+/-1) underwent lobectomy (173 thoracoscopy, 167 thoracotomy). Operative mortality was 5% (17 patients) and overall morbidity was 48% (164 patients). At least one pulmonary complication occurred in 57 patients (17%). Significant predictors of pulmonary complications by multivariable analysis for all patients included Dlco (odds ratio 1.03, p=0.003), FEV1 (odds ratio 1.04, p=0.003), and thoracotomy as surgical approach (odds ratio 3.46, p=0.0007). When patients were analyzed according to operative approach, Dlco and FEV1 remained significant predictors of pulmonary morbidity for patients undergoing thoracotomy but not thoracoscopy.In patients with impaired pulmonary function, preoperative pulmonary function tests are predictors of pulmonary complications when lobectomy for lung cancer is performed through thoracotomy but not through thoracoscopy.

  View details for DOI 10.1016/j.athoracsur.2009.12.065

  View details for Web of Science ID 000275885800005

  View details for PubMedID 20338305

• 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

  View details for DOI 10.1016/j.athoracsur.2005.12.015

  View details for Web of Science ID 000237001700027

• 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

  View details for Web of Science ID 000232956403062

• 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

  View details for Web of Science ID 000231745800084

• 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

  View details for Web of Science ID 000229052500127

• 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

  View details for Web of Science ID 000224648802376

• 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

  View details for Web of Science ID 000224783502205

• 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

  View details for Web of Science ID 000223760800234

• 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

• 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

  View details for Web of Science ID 000186360601766

• 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

  View details for Web of Science ID 000186360602880

• 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

  View details for Web of Science ID 000186360602878

• 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

  View details for Web of Science ID 000186360600040

• 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

  View details for Web of Science ID 000186360602564

• 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

  View details for Web of Science ID 000186360602560

• 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

  View details for DOI 10.1161/01.cir.0000087444.53354.66

  View details for Web of Science ID 000185265000040

• 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

  View details for Web of Science ID 000185248100058

• 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

  View details for Web of Science ID 000183014500061

• 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

  View details for Web of Science ID 000181669502348

• 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

  View details for Web of Science ID 000086784101872