Bio

Bio


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

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

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

Clinical Focus


  • Cancer > Thoracic Oncology
  • Thoracic Surgery

Academic Appointments


Honors & Awards


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

Professional Education


  • Residency:University of PennsylvaniaPA
  • Internship:University of PennsylvaniaPA
  • Medical Education:University of Pennsylvania (1999) PAUnited States of America
  • Residency:Duke University Medical CenterNCUnited States of America
  • Board Certification: Thoracic Surgery, American Board of Thoracic Surgery
  • Board Certification: General Surgery, American Board of Surgery
  • MHS, Duke University, Clinical Research (2012)
  • MD, University of Pennsylvania, Medicine (1999)
  • Post Bac, University of Pennsylvania, Pre-Health (1994)
  • MSE, University of Pennsylvania, Electrical Engineering (1993)
  • B Eng, University of Pennsylvania, Electrical Engineering (1990)

Publications

Journal Articles


  • 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? ANNALS OF SURGICAL ONCOLOGY Erhunmwunsee, L., Englum, B. R., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2015; 22 (3): 1020-1025

    Abstract

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

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

    View details for Web of Science ID 000350553100049

  • 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

  • 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

  • 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

  • Use of Amiodarone After Major Lung Resection ANNALS OF THORACIC SURGERY Berry, M. F., D'Amico, T. A., Onaitis, M. W. 2014; 98 (4): 1199-1206
  • Thoracoscopic Left Upper Lobectomy in Patients With Internal Mammary Artery Coronary Bypass Grafts ANNALS OF THORACIC SURGERY Shah, A. A., Worni, M., Onaitis, M. W., Balderson, S. S., Harpole, D. H., D'Amico, T. A., Berry, M. F. 2014; 98 (4): 1207-1213
  • Trends and outcomes in the use of surgery and radiation for the treatment of locally advanced esophageal cancer: a propensity score adjusted analysis of the surveillance, epidemiology, and end results registry from 1998 to 2008 DISEASES OF THE ESOPHAGUS Worni, M., Castleberry, A. W., Gloor, B., Pietrobon, R., Haney, J. C., D'Amico, T. A., Akushevich, I., Berry, M. F. 2014; 27 (7): 662-669

    Abstract

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

    View details for DOI 10.1111/dote.12123

    View details for Web of Science ID 000341150600009

    View details for PubMedID 23937253

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

    Abstract

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

    View details for DOI 10.1016/j.jamcollsurg.2014.01.062

    View details for Web of Science ID 000341415100025

    View details for PubMedID 24862885

  • 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

  • The impact of pulmonary hypertension on morbidity and mortality following major lung resection EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Wei, B., D'Amico, T., Samad, Z., Hasan, R., Berry, M. F. 2014; 45 (6): 1028-1033

    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 JOURNAL OF 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. 2014; 33 (4): S60-S60
  • Differential prognostic significance of extralobar and intralobar nodal metastases in patients with surgically resected stage II non-small cell lung cancer JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Haney, J. C., Hanna, J. M., Berry, M. F., Harpole, D. H., D'Amico, T. A., Tong, B. C., Onaitis, M. W. 2014; 147 (4): 1164-1168

    Abstract

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

    View details for DOI 10.1016/j.jtcvs.2013.12.015

    View details for Web of Science ID 000332772200019

    View details for PubMedID 24507984

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

    Abstract

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

    View details for DOI 10.1016/j.jamcollsurg.2013.12.005

    View details for Web of Science ID 000331718400020

    View details for PubMedID 24559956

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

    View details for DOI 10.1016/j.athoracsur.2013.09.056

    View details for PubMedID 24384211

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

    Abstract

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

    View details for DOI 10.1016/j.athoracsur.2013.09.016

    View details for Web of Science ID 000329155900043

    View details for PubMedID 24206972

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

    Abstract

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

    View details for DOI 10.1016/j.athoracsur.2014.05.068

    View details for PubMedID 25110335

  • Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / I.S.D.E Speicher, P. J., Wang, X., Englum, B. R., Ganapathi, A. M., Yerokun, B., Hartwig, M. G., D'Amico, T. A., Berry, M. F. 2014

    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

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

    View details for DOI 10.1016/j.athoracsur.2013.07.041

    View details for PubMedID 24182495

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

    Abstract

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

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

    View details for Web of Science ID 000324675700005

    View details for PubMedID 24040521

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

    Abstract

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

    View details for DOI 10.1097/JTO.0b013e3182897bf1

    View details for Web of Science ID 000319258000021

    View details for PubMedID 24614244

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

    Abstract

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

    View details for DOI 10.1097/JTO.0b013e31828916aa

    View details for Web of Science ID 000319258000013

    View details for PubMedID 23571473

  • Diabetes mellitus: A significant co-morbidity in the setting of lung cancer? THORACIC CANCER Washington, I., Chino, J. P., Marks, L. B., D'Amico, T. A., Berry, M. F., Ready, N. E., Higgins, K. A., Yoo, D. S., Kelsey, C. R. 2013; 4 (2): 123-130
  • Does Pneumonectomy Have a Role in the Treatment of Stage IIIA Non-Small Cell Lung Cancer? ANNALS OF THORACIC SURGERY Shah, A. A., Worni, M., Kelsey, C. R., Onaitis, M. W., D'Amico, T. A., Berry, M. F. 2013; 95 (5): 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 JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Villamizar, N. R., Darrabie, M., Hanna, J., Onaitis, M. W., Tong, B. C., D'Amico, T. A., Berry, M. F. 2013; 145 (2): 514-521

    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 BRITISH JOURNAL OF SURGERY Worni, M., Gloor, B., Pietrobon, R., D'Amico, T. A., Akushevich, I., Berry, M. F. 2012; 99: 8-8
  • Induction Chemoradiation Is Not Superior to Induction Chemotherapy Alone in Stage IIIA Lung Cancer ANNALS OF THORACIC SURGERY Shah, A. A., Berry, M. F., Tzao, C., Gandhi, M., Worni, M., Pietrobon, R., D'Amico, T. A. 2012; 93 (6): 1807-1812

    Abstract

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

    View details for DOI 10.1016/j.athoracsur.2012.03.018

    View details for Web of Science ID 000304460000017

    View details for PubMedID 22632486

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

    Abstract

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

    View details for DOI 10.1016/j.ijrobp.2011.07.018

    View details for Web of Science ID 000303920800059

    View details for PubMedID 22208965

  • Outcomes after treatment of resectable, node-negative esophageal cancer: A risk-adjusted analysis of the Surveillance, Epidemiology, and End Results registry JOURNAL OF CLINICAL ONCOLOGY Martin, J. T., Worni, M., Zwischenberger, J. B., Pietrobon, R., D'Amico, T. A., Berry, M. F. 2012; 30 (15)
  • Feasibility of hybrid thoracoscopic lobectomy and en-bloc chest wall resection(dagger) EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Berry, M. F., Onaitis, M. W., Tong, B. C., Balderson, S. S., Harpole, D. H., D'Amico, T. A. 2012; 41 (4): 888-892

    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

  • Outcomes After Surgical Management of Synchronous Bilateral Primary Lung Cancers ANNALS OF THORACIC SURGERY Shah, A. A., Barfield, M. E., Kelsey, C. R., Onaitis, M. W., Tong, B., Harpole, D., D'Amico, T. A., Berry, M. F. 2012; 93 (4): 1055-1060

    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

  • 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 JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 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. 2012; 143 (4): 962-966

    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

  • 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 JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Higgins, K. A., Chino, J. P., Ready, N., Onaitis, M. W., Berry, M. F., D'Amico, T. A., Kelsey, C. R. 2011; 142 (5): 1175-1179

    Abstract

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

    View details for DOI 10.1016/j.jtcvs.2011.07.059

    View details for Web of Science ID 000296337500033

    View details for PubMedID 22014344

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

    Abstract

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

    View details for DOI 10.1016/j.thorsurg.2011.04.004

    View details for PubMedID 21762860

  • INDUCTION CHEMORADIOTHERAPY IS NOT SUPERIOR TO INDUCTION CHEMOTHERAPY ALONE IN PATIENTS WITH STAGE IIIA(N2) NON-SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS JOURNAL OF THORACIC ONCOLOGY Shah, A. A., Berry, M. F., Tzao, C., Rajgor, D., Pietrobon, R., D'Amico, T. A. 2011; 6 (6): S1578-S1579
  • PERSISTENT N2 DISEASE AFTER NEOADJUVANT CHEMOTHERAPY-NOW WHAT? JOURNAL OF THORACIC ONCOLOGY 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. 2011; 6 (6): S1572-S1572
  • A model for morbidity after lung resection in octogenarians EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Berry, M. F., Onaitis, M. W., Tong, B. C., Harpole, D. H., D'Amico, T. A. 2011; 39 (6): 989-994

    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

  • 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 ANNALS OF THORACIC SURGERY Berry, M. F., Villamizar-Ortiz, N. R., Tong, B. C., Burfeind, W. R., Harpole, D. H., D'Amico, T. A., Onaitis, M. W. 2010; 89 (4): 1044-1052

    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
  • 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 CIRCULATION 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. 2005; 112 (17): U503-U503
  • Treatment with granulocyte monocyte colony stimulating factor and stromal cell derived factor-1alpha enhances endothelial progenitor cell mediated myocardial perfusion and viability in ischemic cardiomyopathy JOURNAL 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. 2005; 201 (3): S44-S44
  • Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Woo, Y. J., Grand, T. J., Berry, M. F., Atluri, P., Moise, M. A., Hsu, V. M., Cohen, J., Fisher, O., Burdick, J., Taylor, M., Zentko, S., Liao, G., Smith, M., Kolakowski, S., Jayasankar, V., Gardner, T. J., Sweeney, H. L. 2005; 130 (2): 321-329

    Abstract

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

    View details for DOI 10.1016/j.jtcvs.2004.11.041

    View details for Web of Science ID 000231069700015

    View details for PubMedID 16077394

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

    Abstract

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

    View details for Web of Science ID 000231101300014

    View details for PubMedID 15956929

  • Ischemic heart failure increases local concentrations of the endogenous inotrope apelin-13 and the APJ receptor JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 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. 2005; 38 (5): 850-850
  • 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 JOURNAL OF THORACIC AND CARDIOVASCULAR 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. 2004; 128 (6): 866-875

    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 MOLECULAR BIOLOGY OF THE CELL Engler, A. J., Berry, M., Sweeney, H. L., Discher, D. E. 2004; 15: 298A-298A
  • Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy CIRCULATION Kolakowski, S., Grand, T., Fisher, O., Berry, M., Moise, M. A., Cohen, J., Hsu, V., Woo, Y. J. 2004; 110 (17): 398-398
  • 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 JOURNAL 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. 2004; 199 (3): S105-S105
  • Local myocardial overexpression of growth hormone attenuates postinfarction remodeling and preserves cardiac function ANNALS OF THORACIC SURGERY Jayasankar, V., Bish, L. T., Pirolli, T. J., Berry, M. F., Burdick, J., Woo, Y. J. 2004; 77 (6): 2122-2129

    Abstract

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

    View details for DOI 10.1016/j.athoracsur.2003.12.043

    View details for Web of Science ID 000221717200039

    View details for PubMedID 15172279

  • Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia JOURNAL OF THORACIC AND CARDIOVASCULAR 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. 2004; 127 (5): 1262-1269

    Abstract

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

    View details for DOI 10.1016/j.jtcvs.2003.11.032

    View details for Web of Science ID 000221134600006

    View details for PubMedID 15115981

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

    Abstract

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

    View details for DOI 10.1016/j.yjmcc.2004.01.010

    View details for Web of Science ID 000221181400008

    View details for PubMedID 15081312

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

    Abstract

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

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

    View details for Web of Science ID 000186358600081

    View details for PubMedID 14602321

  • Apelin has in vivo inotropic effects on normal and failing hearts CIRCULATION Berry, M. F., Jayasankar, V., Pirolli, T. J., Burdick, J. W., Morine, K. J., Gardner, T. J., Woo, Y. J. 2003; 108 (17): 550-550
  • Ethyl pyruvate reduces free radical production and preserves cardiac function in a rat model of off-pump coronary bypass CIRCULATION Taylor, M. D., Grand, T. J., Cohen, J. E., Hsu, V., Zentko, S., Berry, M. F., Woo, J. 2003; 108 (17): 549-549
  • Matrix metalloproteinase inhibition by gene transfer of TIMP-1 attenuates ventricular remodeling and preserves cardiac function in ischemic cardiomyopathy CIRCULATION 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. 2003; 108 (17): P-P
  • Mesenchymal stem cell injection into acutely infarcted myocardium decreases fibrosis and apoptosis and significantly preserves ventricular function and geometry CIRCULATION Berry, M. F., Jayasankar, V., Pirolli, T. J., Gardner, T. J., Sweeney, H. L., Woo, Y. J. 2003; 108 (17): 622-622
  • Stromal cell derived factor provides a novel angiogenic therapy for ischemic cardiomyopathy CIRCULATION Woo, Y. J., Grand, T. J., Berry, M., Cohen, J., Hsu, V., Taylor, M., Zentko, S., Burdick, J., Pirolli, T., Jayasankar, V. 2003; 108 (17): 621-622
  • Matrix metalloproteinase inhibition by gene transfer of TIMP-1 attenuates ventricular remodeling and preserves cardiac function in ischemic cardiomyopathy CIRCULATION 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. 2003; 108 (17): 366-366
  • Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure CIRCULATION Jayasankar, V., Woo, Y. J., Bish, L. T., Pirolli, T. J., Chatterjee, S., Berry, M. F., Burdick, J., Gardner, T. J., Sweeney, H. L. 2003; 108 (10): 230-236
  • Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure. Circulation Jayasankar, V., Woo, Y. J., Bish, L. T., Pirolli, T. J., Chatterjee, S., Berry, M. F., Burdick, J., Gardner, T. J., Sweeney, H. L. 2003; 108: II230-6

    Abstract

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

    View details for PubMedID 12970238

  • Local myocardial growth hormone overexpression limits left ventricular dysfunction and remodeling in experimental heart failure JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Jayasankar, V., Berry, M., Bish, L., Pirolli, T., Burdick, J., Gardner, T., Woo, Y. J. 2003; 197 (3): S26-S27
  • Hepatocyte growth factor treatment preserves post-infarction cardiac function CIRCULATION Jayasankar, V., Berry, M. F., Chatterjee, S., Bish, L. T., Pirolli, T. J., Gardner, T. J., Sweeney, H. L., Woo, Y. J. 2003; 107 (19): E139-E139
  • Treatment of experimental heart failure with hepatocyte growth factor JOURNAL 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. 2003; 41 (6): 544A-544A
  • Dexon mesh splenorrhaphy for intraoperative splenic injuries AMERICAN SURGEON Berry, M. F., Rosato, E. F., Williams, N. N. 2003; 69 (2): 176-180

    Abstract

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

    View details for Web of Science ID 000181435900022

    View details for PubMedID 12641363

  • Outcome of pancreaticoduodenectomy and impact of adjuvant therapy for ampullary carcinomas INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lee, J. H., Whittington, R., Williams, N. N., Berry, M. F., Vaughn, D. J., Haller, D. G., Rosato, E. F. 2000; 47 (4): 945-953

    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. GASTROENTEROLOGY Berry, M. F., Williams, N. N., Lee, J. H., Whittington, R., Canter, R. J., Rosato, E. F. 2000; 118 (4): A1504-A1505

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