D J Sugarbaker

Summary

Affiliation: Massachusetts General Hospital
Country: USA

Publications

  1. doi request reprint Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection
    David J Sugarbaker
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 145:955-63. 2013
  2. pmc Differentially expressed alternatively spliced genes in malignant pleural mesothelioma identified using massively parallel transcriptome sequencing
    Lingsheng Dong
    The Thoracic Surgery Oncology Laboratory and Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    BMC Med Genet 10:149. 2009
  3. pmc Genes associated with prognosis after surgery for malignant pleural mesothelioma promote tumor cell survival in vitro
    Gavin J Gordon
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    BMC Cancer 11:169. 2011
  4. doi request reprint Clinical and pathological features of three-year survivors of malignant pleural mesothelioma following extrapleural pneumonectomy
    David J Sugarbaker
    Division of Thoracic Surgery and Department of Pathology, Brigham and Women s Hospital, Boston, MA, USA
    Eur J Cardiothorac Surg 40:298-303. 2011
  5. pmc Lung cancer. 6: The case for limited surgical resection in non-small cell lung cancer
    D J Sugarbaker
    Harvard Medical School, Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA, USA
    Thorax 58:639-41. 2003
  6. ncbi request reprint Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies
    David J Sugarbaker
    Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 128:138-46. 2004
  7. doi request reprint Surgery for malignant pleural mesothelioma
    David J Sugarbaker
    Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Expert Rev Respir Med 4:363-72. 2010
  8. ncbi request reprint Macroscopic complete resection: the goal of primary surgery in multimodality therapy for pleural mesothelioma
    David J Sugarbaker
    Department of Surgery, Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Thorac Oncol 1:175-6. 2006
  9. doi request reprint Diagnostic workup of lung cancer
    David J Sugarbaker
    Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115 6195, USA
    Surg Oncol Clin N Am 20:667-79. 2011
  10. ncbi request reprint Inhibitor of apoptosis proteins are regulated by tumour necrosis factor-alpha in malignant pleural mesothelioma
    G J Gordon
    The Thoracic Surgery Oncology Laboratory and the Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    J Pathol 211:439-46. 2007

Research Grants

  1. CANCER AND LEUKEMIA GROUP B
    David Sugarbaker; Fiscal Year: 2002

Detail Information

Publications101 found, 100 shown here

  1. doi request reprint Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection
    David J Sugarbaker
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 145:955-63. 2013
    ..We investigated whether hyperthermic intraoperative cisplatin chemotherapy lavage affects the interval to recurrence and overall survival among patients with favorable prognostic factors...
  2. pmc Differentially expressed alternatively spliced genes in malignant pleural mesothelioma identified using massively parallel transcriptome sequencing
    Lingsheng Dong
    The Thoracic Surgery Oncology Laboratory and Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    BMC Med Genet 10:149. 2009
    ..We hypothesized that alternative splicing profiles might be detected in the sequencing data for the expressed genes in these samples...
  3. pmc Genes associated with prognosis after surgery for malignant pleural mesothelioma promote tumor cell survival in vitro
    Gavin J Gordon
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    BMC Cancer 11:169. 2011
    ..In this study, we determined whether any of these four genes could be linked to a cancer relevant phenotype...
  4. doi request reprint Clinical and pathological features of three-year survivors of malignant pleural mesothelioma following extrapleural pneumonectomy
    David J Sugarbaker
    Division of Thoracic Surgery and Department of Pathology, Brigham and Women s Hospital, Boston, MA, USA
    Eur J Cardiothorac Surg 40:298-303. 2011
    ..We explored factors associated with 3-year survival in patients with malignant pleural mesothelioma, who underwent extrapleural pneumonectomy, to help refine patient selection criteria for surgery and other therapies...
  5. pmc Lung cancer. 6: The case for limited surgical resection in non-small cell lung cancer
    D J Sugarbaker
    Harvard Medical School, Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA, USA
    Thorax 58:639-41. 2003
    ..The choice between conservative resection or standard anatomical resection for stage I NSCLC depends on the size and biology of the tumour and the age and state of health of the patient...
  6. ncbi request reprint Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies
    David J Sugarbaker
    Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 128:138-46. 2004
    ..Complications after extrapleural pneumonectomy were further analyzed to elucidate means of prevention, early detection, and treatment...
  7. doi request reprint Surgery for malignant pleural mesothelioma
    David J Sugarbaker
    Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Expert Rev Respir Med 4:363-72. 2010
    ..Pending the discovery of new drugs, the focus of clinical research over the next 5 years will emphasize refinements in patient selection, pathologic staging, molecular staging and other novel adjuvant therapies...
  8. ncbi request reprint Macroscopic complete resection: the goal of primary surgery in multimodality therapy for pleural mesothelioma
    David J Sugarbaker
    Department of Surgery, Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Thorac Oncol 1:175-6. 2006
  9. doi request reprint Diagnostic workup of lung cancer
    David J Sugarbaker
    Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115 6195, USA
    Surg Oncol Clin N Am 20:667-79. 2011
    ..The two major histologic types of lung cancer are small cell lung cancer and non-small cell lung cancer. The diagnosis and management of lung cancer requires a multidisciplinary approach...
  10. ncbi request reprint Inhibitor of apoptosis proteins are regulated by tumour necrosis factor-alpha in malignant pleural mesothelioma
    G J Gordon
    The Thoracic Surgery Oncology Laboratory and the Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    J Pathol 211:439-46. 2007
    ....
  11. ncbi request reprint New surgical options for elderly lung cancer patients
    M T Jaklitsch
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Chest 116:480S-485S. 1999
    ..Age alone should not be a contradiction to thoracic surgical interventions when video thoracoscopy is performed as treatment...
  12. ncbi request reprint Transthoracic esophagectomy with radical mediastinal and abdominal lymph node dissection and cervical esophagogastrostomy for esophageal carcinoma
    S J Swanson
    Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Ann Thorac Surg 72:1918-24; discussion 1924-5. 2001
    ..The technique includes right thoracotomy, laparotomy, and cervical esophagogastrostomy (total thoracic esophagectomy) with radical mediastinal and abdominal lymph node dissection...
  13. pmc Four-gene expression ratio test for survival in patients undergoing surgery for mesothelioma
    Gavin J Gordon
    Department of Surgery, Division of Thoracic Surgery, Harvard Medical School and Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    J Natl Cancer Inst 101:678-86. 2009
    ..In this study, we investigated the predictive value and technical assay performance of this test in patients with malignant pleural mesothelioma...
  14. doi request reprint Pneumonectomy after chemoradiation: the Dana-Farber Cancer Institute/Brigham and Women's Hospital experience
    Aaron M Allen
    Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer 112:1106-13. 2008
    ..The current study was conducted to examine the outcomes of pneumonectomy after induction chemoradiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC)...
  15. ncbi request reprint Sequential thoracic metastasectomy prolongs survival by re-establishing local control within the chest
    M T Jaklitsch
    Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 121:657-67. 2001
    ..CONCLUSIONS: Multiple attempts to re-establish intrathoracic control of metastatic disease is justified in carefully selected patients, but the magnitude of benefit decays with each subsequent attempt...
  16. ncbi request reprint Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications
    D J Kwiatkowski
    Division of Experimental Medicine, Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Clin Oncol 16:2468-77. 1998
    ..To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design a molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC)...
  17. ncbi request reprint Relationship between a history of antecedent cancer and the probability of malignancy for a solitary pulmonary nodule
    Carlos M Mery
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Chest 125:2175-81. 2004
    ..To determine the probability of malignancy for a solitary pulmonary nodule (SPN) as a function of cancer history...
  18. doi request reprint Morbidity, mortality, mean survival, and the impact of histology on survival after pleurectomy in 64 patients with malignant pleural mesothelioma
    Siyamek Neragi-Miandoab
    Department of Surgery, Cardiothoracic Surgery, Boston University Medical Center, School of Medicine, One Boston Medical Center Place, Boston MA 02118, USA
    Int J Surg 6:293-7. 2008
    ....
  19. pmc Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups
    Gary M Strauss
    Tufts Medical Center, Division of Medical Oncology, Tufts NEMC, Boston, MA 02111, USA
    J Clin Oncol 26:5043-51. 2008
    ..This report provides a mature analysis of Cancer and Leukemia Group B (CALGB) 9633, the only RCT designed specifically for stage IB NSCLC...
  20. ncbi request reprint Treatment of malignant mesothelioma
    M T Jaklitsch
    Department of Surgery, Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA
    World J Surg 25:210-7. 2001
    ..Innovative therapies such as the use of photodynamic, targeted cytokines and gene therapy are currently being investigated for management of MPM...
  21. doi request reprint AXL regulates mesothelioma proliferation and invasiveness
    W B Ou
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Oncogene 30:1643-52. 2011
    ..AXL inhibition suppressed mesothelioma anchorage-independent growth, with reduction in colony numbers and size. These studies suggest that AXL inhibitors warrant clinical evaluation in mesothelioma...
  22. ncbi request reprint Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma
    Aaron M Allen
    Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Boston, MA, USA
    Int J Radiat Oncol Biol Phys 65:640-5. 2006
    ..To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy...
  23. ncbi request reprint Influence of radiotherapy technique and dose on patterns of failure for mesothelioma patients after extrapleural pneumonectomy
    Aaron M Allen
    Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Int J Radiat Oncol Biol Phys 68:1366-74. 2007
    ..We compared the outcomes after moderate-dose hemithoracic radiotherapy (MDRT) and high-dose hemithoracic RT (HDRT) after EPP for malignant pleural mesothelioma...
  24. doi request reprint Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study
    Tamara R Tilleman
    Department of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 138:405-11. 2009
    ..We sought to prospectively determine the feasibility and safety of hyperthermic intraoperative intracavitary cisplatin perfusion immediately after extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma...
  25. ncbi request reprint Prevalence of in vitro chemotherapeutic drug resistance in primary malignant pleural mesothelioma: result in a cohort of 203 resection specimens
    Aneil A Mujoomdar
    Division of Thoracic Surgery, Department of Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 140:352-5. 2010
    ..In vitro chemotherapy resistance in human mesothelioma has not been reported. Our goal was to determine the prevalence of drug resistance in a large sample of malignant pleural mesothelioma using a commercially available assay...
  26. ncbi request reprint Surveillance transbronchial lung biopsies: implication for survival after lung transplantation
    S J Swanson
    Lung Transplant Program, Brigham and Women s Hospital, Harvard Medical School, Boston, Mass, USA
    J Thorac Cardiovasc Surg 119:27-37. 2000
    ..We wished to determine whether early rejection after lung transplantation as assessed by surveillance transbronchial biopsy predicts for survival...
  27. doi request reprint Current trends in radiologic management of malignant pleural mesothelioma
    Ritu R Gill
    Department of Radiology, Division of Thoracic Surgery, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Semin Thorac Cardiovasc Surg 21:111-20. 2009
    ..This review focuses on the practical aspects of the radiological assessment of MPM, highlighting the role of the radiologist in preoperative and postoperative evaluation with a multimodality approach...
  28. doi request reprint Outcomes of patients with stage III nonsmall cell lung cancer treated with chemotherapy and radiation with and without surgery
    Hale B Caglar
    Department of Radiation Oncology Dana Farber Cancer Institute Brigham and Women s Hospital, Boston, Massachusetts 02215, USA
    Cancer 115:4156-66. 2009
    ..The objective of this study was to identify the factors associated with improved outcome after treatment for stage III nonsmall cell lung cancer (NSCLC)...
  29. ncbi request reprint Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma
    Gavin J Gordon
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Carcinogenesis 23:1017-24. 2002
    ..Our observations strongly suggest that IAP-1 is at least partly responsible for promoting carcinogenesis and mediating resistance to cisplatin in many MPM tumors and that further study of this apoptotic pathway is warranted...
  30. doi request reprint A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma
    Lambros Zellos
    Division of Thoracic Surgery and Department of Pathology, Brigham and Women s Hospital, Boston, Mass, USA
    J Thorac Cardiovasc Surg 137:453-8. 2009
    ..This study was undertaken to determine maximum tolerated dose and toxicity of intraoperative intracavitary hyperthermic cisplatin perfusion with amifostine after extrapleural pneumonectomy for malignant pleural mesothelioma...
  31. ncbi request reprint Using gene expression ratios to predict outcome among patients with mesothelioma
    Gavin J Gordon
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Natl Cancer Inst 95:598-605. 2003
    ..We examined whether this technique could predict treatment-related outcome for patients with mesothelioma...
  32. doi request reprint Surgical techniques for multimodality treatment of malignant pleural mesothelioma: extrapleural pneumonectomy and pleurectomy/decortication
    Andrea S Wolf
    Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, Massachusettes 02115, USA
    Semin Thorac Cardiovasc Surg 21:132-48. 2009
    ..Both operations are technically complex and should only be performed at experienced high-volume centers...
  33. ncbi request reprint Expression patterns of inhibitor of apoptosis proteins in malignant pleural mesothelioma
    G J Gordon
    The Thoracic Surgery Oncology Laboratory and the Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    J Pathol 211:447-54. 2007
    ..Only IAP-1 and livin protein was expressed in the nucleus of MPM tumours. These results provide the rationale for additional study of this gene family in MPM and cancer in general...
  34. ncbi request reprint Lung cancer staging and treatment in multidisciplinary trials: Cancer and Leukemia Group B cooperative group approach. Thoracic Surgeons of CALGB
    M J Krasna
    Division of Thoracic Surgery, University of Maryland Medical School, Baltimore 21201, USA
    Ann Thorac Surg 68:201-7. 1999
    ..Less than 1% of lung cancer patients in the United States are currently being treated in a clinical trial. Only with results from large, prospective trials can the questions of neoadjuvant and adjuvant therapy be answered...
  35. ncbi request reprint CALGB 9380: a prospective trial of the feasibility of thoracoscopy/laparoscopy in staging esophageal cancer
    M J Krasna
    Division of Thoracic Surgery, University of Maryland Medical System, Baltimore 21201, USA
    Ann Thorac Surg 71:1073-9. 2001
    ..We report the experience of an Intergroup NCI trial (CALGB 9380) evaluating the feasibility and accuracy of this staging modality...
  36. ncbi request reprint Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease
    O S Breathnach
    Lowe Center for Thoracic Oncology, Division of Experimental Medicine, Department of Adult Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Thorac Cardiovasc Surg 121:42-7. 2001
    ..Further research is warranted to define the etiology, clinical course, and molecular abnormalities in patients with bronchioloalveolar carcinoma to generate more effective therapeutic approaches...
  37. ncbi request reprint Primary Ewing sarcoma invading the heart: resection and reconstruction
    Subroto Paul
    Division of Thoracic Surgery, Department of Surgery, Brigham and Women s Hospital, Boston, Mass 02115, USA
    J Thorac Cardiovasc Surg 133:1667-9. 2007
  38. doi request reprint Hyperthermic chemoperfusion for the treatment of malignant pleural mesothelioma
    Aneil A Mujoomdar
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Semin Thorac Cardiovasc Surg 20:298-304. 2008
    ..Further trials are being performed with a multidrug combination following macroscopic complete resection...
  39. doi request reprint Incidence of atrial fibrillation after extrapleural pneumonectomy vs. pleurectomy in patients with malignant pleural mesothelioma
    Siyamek Neragi-Miandoab
    Department of Surgery, St Vincent Medical Center, New York Medical College, School of Medicine, New York, NY 10011, USA
    Interact Cardiovasc Thorac Surg 7:1039-42. 2008
    ..We conclude that EPP vs. pleurectomy and age over 65 years are risk factors for postoperative AF. The increased odds of having AF after EPP could be due to right heart stress caused by pneumonectomy...
  40. ncbi request reprint Diffuse malignant mesothelioma of the pleural space and its management
    Lambros S Zellos
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Oncology (Williston Park) 16:907-13; discussion 916-7, 919-20, 925. 2002
    ..However, innovative therapies are still needed to prolong survival in patients with early and advanced disease...
  41. ncbi request reprint A prognostic test for adenocarcinoma of the lung from gene expression profiling data
    Gavin J Gordon
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Epidemiol Biomarkers Prev 12:905-10. 2003
    ..Our results provide additional evidence that expression ratios are highly accurate in predicting cancer recurrence and may be used in a simple test to predict response to surgical therapy in early-stage lung adenocarcinoma...
  42. ncbi request reprint Malignant pleural mesothelioma: overview of the North American and European experience
    Jasleen Kukreja
    Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Thorac Surg Clin 14:435-45. 2004
    ....
  43. pmc EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer
    Jussi P Koivunen
    Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, D820A, 44 Binney Street, Boston, MA 02115, USA
    Clin Cancer Res 14:4275-83. 2008
    ..We determined the frequency of EML4-ALK in Caucasian NSCLC and in NSCLC cell lines. We also determined whether TAE684, a specific ALK kinase inhibitor, would inhibit the growth of EML4-ALK-containing cell lines in vitro and in vivo...
  44. ncbi request reprint Modified T-tube repair of delayed esophageal perforation results in a low mortality rate similar to that seen with acute perforations
    Philip A Linden
    Division of Thoracic Surgery, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Ann Thorac Surg 83:1129-33. 2007
    ..We present a large series of patients requiring operative treatment of esophageal perforations with attention to an infrequently used method of dealing with delayed intrathoracic perforations...
  45. ncbi request reprint Effectiveness of trichostatin A as a potential candidate for anticancer therapy in non-small-cell lung cancer
    Nishit K Mukhopadhyay
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
    Ann Thorac Surg 81:1034-42. 2006
    ....
  46. ncbi request reprint Phase I to II study of pleurectomy/decortication and intraoperative intracavitary hyperthermic cisplatin lavage for mesothelioma
    William G Richards
    Brigham and Women s Hospital, Boston, MA 02115, USA
    J Clin Oncol 24:1561-7. 2006
    ..To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM)...
  47. ncbi request reprint Morbidity of lung resection after prior lobectomy: results from the Veterans Affairs National Surgical Quality Improvement Program
    Philip A Linden
    Division of Thoracic Surgery, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Ann Thorac Surg 83:425-31; discussion 432. 2007
    ..The risks of repeat lung resection have not been well quantified or analyzed. We used a national, prospectively recorded database to evaluate the complication rate and risk factors in this population...
  48. pmc Transcriptome sequencing of malignant pleural mesothelioma tumors
    David J Sugarbaker
    International Mesothelioma Program, Division of Thoracic Surgery, Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:3521-6. 2008
    ..Of the seven point mutations, three were observed in at least one tumor from 49 other MPM patients. The mutations were in genes that could be causally related to cancer and included XRCC6, PDZK1IP1, ACTR1A, and AVEN...
  49. ncbi request reprint Nodal downstaging predicts survival following induction chemotherapy for stage IIIA (N2) non-small cell lung cancer in CALGB protocol #8935
    Michael T Jaklitsch
    Division of Thoracic Surgery, Brigham and Women s Hospital, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    J Surg Oncol 94:599-606. 2006
    ..Induction cisplatin/vinblastine chemotherapy was followed by surgical resection, adjuvant cisplatin/vinblastine, and radiotherapy. We now evaluate the prognosis of pathologic nodes...
  50. pmc Asbestos exposure predicts cell cycle control gene promoter methylation in pleural mesothelioma
    Brock C Christensen
    Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
    Carcinogenesis 29:1555-9. 2008
    ..These data suggest a novel tumorigenic mechanism of action of asbestos and may contribute to the understanding of precisely how asbestos exposure influences the etiology and clinical course of malignant mesothelioma...
  51. ncbi request reprint Preclinical studies of the proteasome inhibitor bortezomib in malignant pleural mesothelioma
    Gavin J Gordon
    The Thoracic Surgery Oncology Laboratory and the Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA
    Cancer Chemother Pharmacol 61:549-58. 2008
    ..Bortezomib may improve outcome in MPM patients alone or in combination with standard chemotherapy but the order of administration is likely to be important. This study justifies further evaluation of bortezomib in MPM...
  52. ncbi request reprint Percutaneous treatment of high-output chylothorax with embolization or needle disruption technique
    Christoph A Binkert
    Department of Radiology, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA
    J Vasc Interv Radiol 16:1257-62. 2005
    ..The median times to chest tube removal were 7 days in the embolization group and 3.5 days in the needle disruption group...
  53. ncbi request reprint The use of cardiopulmonary bypass during resection of locally advanced thoracic malignancies: a 10-year two-center experience
    John G Byrne
    The Division of Cardiac Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    Chest 125:1581-6. 2004
    ..The availability of CPB also provides a safety net in the event of injury to vascular structures during tumor resection...
  54. doi request reprint Diffusion-weighted MRI of malignant pleural mesothelioma: preliminary assessment of apparent diffusion coefficient in histologic subtypes
    Ritu R Gill
    Department of Radiology, Brigham and Women s Hospital, Boston, MA 02115, USA
    AJR Am J Roentgenol 195:W125-30. 2010
    ....
  55. ncbi request reprint Surgery for early stage non-small cell lung cancer
    Michael Y Chang
    Harvard Medical School and Division of Thoracic Surgery, Brigham and Women s Hospital 75 Francis Street Boston, MA 02115, USA
    Semin Surg Oncol 21:74-84. 2003
    ..Methods that identify early-stage lung cancer patients at greatest risk for recurrence are needed to identify patients who may benefit from additional therapies...
  56. doi request reprint Characteristics of malignant pleural mesothelioma in women
    Andrea S Wolf
    Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, Massachusetts 02215, USA
    Ann Thorac Surg 90:949-56; discussion 956. 2010
    ..Women also appear to experience better long-term survival. This study evaluates the role of gender in relation to established prognostic factors in MPM...
  57. ncbi request reprint Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study
    Lori J Wirth
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Clin Cancer Res 9:1698-704. 2003
    ..To determine the maximum-tolerated dose of docetaxel (DOC) in combination with carboplatin (CAR) and thoracic radiotherapy (RT), in the setting of trimodality treatment of patients with stage III non-small cell lung cancer (NSCLC)...
  58. ncbi request reprint Cardiac decortication (epicardiectomy) for occult constrictive cardiac physiology after left extrapleural pneumonectomy
    John G Byrne
    Cardiac Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA, USA
    Chest 122:2256-9. 2002
    ..When patients present with dyspnea, hepatojugular reflux, and peripheral edema refractory to diuretics, constrictive cardiac physiology should be considered in the differential diagnosis, even in the absence of parietal pericardium...
  59. ncbi request reprint Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma
    Gavin J Gordon
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 62:4963-7. 2002
    ..Furthermore, we provide evidence suggesting that this technique can be equally accurate in other clinical scenarios...
  60. ncbi request reprint Current surgical management of malignant pleural mesothelioma
    Lambros Zellos
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Curr Oncol Rep 4:354-60. 2002
    ..The lack of cure in any of the published protocols demonstrates the need for new therapies and approaches for this disease...
  61. ncbi request reprint Integrin-dependent protein tyrosine phosphorylation is a key regulatory event in collagen-IV-mediated adhesion and proliferation of human lung tumor cell line, Calu-1
    Nishit K Mukhopadhyay
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Ann Thorac Surg 78:450-7. 2004
    ..During invasion, tumor cells attach to the basement membrane protein, collagen type IV, degrade it, migrate through blood vessels, and adhere to extracellular matrix proteins...
  62. ncbi request reprint Pleural biopsy: a reliable method for determining the diagnosis but not subtype in mesothelioma
    Raphael Bueno
    Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    Ann Thorac Surg 78:1774-6. 2004
    ..Pleural biopsy has been proposed as the diagnostic gold standard. We investigated the accuracy of open pleural biopsy for diagnosis and subtype identification in MPM...
  63. pmc Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling
    Gavin J Gordon
    Thoracic Surgery Oncology Laboratory, Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Am J Pathol 166:1827-40. 2005
    ..Finally, we used bioinformatics tools (ie, software) to create and explore complex physiological pathways. Combined, all of these data may advance our understanding of mesothelioma tumorigenesis, pathobiology, or both...
  64. doi request reprint Proposed adjustments to pathologic staging of epithelial malignant pleural mesothelioma based on analysis of 354 cases
    William G Richards
    Division of Thoracic Surgery, Brigham and Women s Hospital, Thoracic Surgery, 75 Francis Street, Boston, MA 02115, USA
    Cancer 116:1510-7. 2010
    ..Interpretation of prior studies that correlate pathologic factors with outcome has been confounded by the inclusion of patients undergoing differing surgical procedures and with varied tumor histology...
  65. doi request reprint Managing the pneumonectomy space after extrapleural pneumonectomy: postoperative intrathoracic pressure monitoring
    Andrea S Wolf
    Division of Thoracic Surgery and Department of Radiology, Brigham and Women s Hospital, Boston, MA 02215, USA
    Eur J Cardiothorac Surg 37:770-5. 2010
    ..In this retrospective analysis, we evaluate the efficacy of intrathoracic pressure monitoring and intermittent fluid aspiration to manage the pneumonectomy space in the early postoperative period following extrapleural pneumonectomy...
  66. ncbi request reprint Laparoscopic fundoplication in patients with end-stage lung disease awaiting transplantation
    Philip A Linden
    Division of Thoracic Surgery, Brigham and Women s Hospital and Harvard Medical School, Boston, Mass 02115, USA
    J Thorac Cardiovasc Surg 131:438-46. 2006
    ..We evaluated the risk and physiologic effect of laparoscopic fundoplication in patients on the lung transplant waiting list...
  67. ncbi request reprint High risk of brain metastases in surgically staged IIIA non-small-cell lung cancer patients treated with surgery, chemotherapy, and radiation
    Harvey J Mamon
    Department of Radiation Oncology and Medical Oncology, Dana Farber Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    J Clin Oncol 23:1530-7. 2005
    ..We sought to review our experience with surgically staged IIIA (N2) non-small-cell lung cancer (NSCLC), focusing on the patterns of failure in consecutively treated patients from 1988 to 2000...
  68. ncbi request reprint Similar long-term survival of elderly patients with non-small cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology, and end results database
    Carlos M Mery
    Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Chest 128:237-45. 2005
    ..To determine the effect of age and type of surgery on long-term survival in patients with early-stage non-small cell lung cancer (NSCLC)...
  69. ncbi request reprint Lung resection in patients with preoperative FEV1 < 35% predicted
    Philip A Linden
    Division of Thoracic Surgery, Brigham and Women s Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115, USA
    Chest 127:1984-90. 2005
    ..To determine the morbidity, mortality, and feasibility of lung resection in patients with tumors and preoperative FEV1 < 35% predicted...
  70. pmc Validation of genomics-based prognostic tests in malignant pleural mesothelioma
    Gavin J Gordon
    Thoracic Surgery Oncology Laboratory and Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Clin Cancer Res 11:4406-14. 2005
    ..In this report, we examine the accuracy of a previously proposed prognostic test in an independent cohort of MPM patients. This test uses simple ratios of gene expression levels to provide a novel prognostication scheme...
  71. pmc Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients
    J P Koivunen
    Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Br J Cancer 99:245-52. 2008
    ..002). The outcome of stages I and II NSCLC patients treated with surgery alone did not significantly differ based on LKB1 mutation status. Our study provides clinical and molecular characteristics of NSCLC, which harbour LKB1 mutations...
  72. pmc Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses
    A Bhattacharjee
    Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 98:13790-5. 2001
    ..These results suggest that integration of expression profile data with clinical parameters could aid in diagnosis of lung cancer patients...
  73. ncbi request reprint Insulin receptor activation in solitary fibrous tumours
    Y Li
    Department of Pathology, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    J Pathol 211:550-4. 2007
    ..The aetiological relevance of IGF-2 is supported by expression of IR-A, the IR isoform with high affinity for IGF-2, in all SFTs. Our studies suggest that IR activation plays an oncogenic role in SFTs...
  74. ncbi request reprint Combined antegrade and retrograde dilation: a new endoscopic technique in the management of complex esophageal obstruction
    R Bueno
    Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Gastrointest Endosc 54:368-72. 2001
    ..All strictures were dilated and no perforations occurred. CONCLUSIONS: Combined antegrade and retrograde dilation is a safe and effective technique for dilation of complex obstructing esophageal lesions...
  75. pmc Health-related quality of life after elective surgery: measurement of longitudinal changes
    C M Mangione
    Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA
    J Gen Intern Med 12:686-97. 1997
    ....
  76. ncbi request reprint Innovative therapies: intraoperative intracavitary chemotherapy
    Michael Y Chang
    Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Thorac Surg Clin 14:549-56. 2004
    ..By approaching the problem of local recurrence after resection of MPM in a careful and methodical manner, we hope to decrease or delay the rate of recurrence and potentially improve longterm survival in patients with this lethal disease...
  77. ncbi request reprint Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma: techniques and complications
    Michael Y Chang
    Division of Thoracic Surgery, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Thorac Surg Clin 14:523-30. 2004
    ..Although mesothelioma remains a difficult disease to treat, the techniques of surgical resection for mesothelioma have improved dramatically. Currently, EPP can be performed with acceptable morbidity and mortality at experienced centers...
  78. ncbi request reprint Frequent HIN-1 promoter methylation and lack of expression in multiple human tumor types
    Ian Krop
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, D740C, Boston, MA 02115, USA
    Mol Cancer Res 2:489-94. 2004
    ..Thus, silencing of HIN-1 expression and methylation of its promoter occurs in multiple human cancer types, suggesting that elimination of HIN-1 function may contribute to several forms of epithelial tumorigenesis...
  79. ncbi request reprint Menopausal effects on presentation, treatment, and survival of women with non-small cell lung cancer
    Kimberly A Moore
    Division of Thoracic Surgery, Department of General Surgery, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Ann Thorac Surg 76:1789-95. 2003
    ..Because human NSCLC cells express estrogen receptors, we evaluated hormonally active and inactive women to identify biologically mediated differences...
  80. pmc Asbestos burden predicts survival in pleural mesothelioma
    Brock C Christensen
    Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
    Environ Health Perspect 116:723-6. 2008
    ..Malignant pleural mesothelioma (MPM) is a rapidly fatal asbestos-associated malignancy with a median survival time of <1 year following diagnosis. Treatment strategy is determined in part using known prognostic factors...
  81. ncbi request reprint Factors predicting poor survival after resection of stage IA non-small cell lung cancer
    Michael Y Chang
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, and Boston VA Healthcare, Harvard School of Public Health, Boston, Mass, USA
    J Thorac Cardiovasc Surg 134:850-6. 2007
    ..Using a national cancer registry, we determined the postoperative survival of patients with stage IA non-small cell lung cancer in the United States from 1988 to 1997 and identified factors that affect survival...
  82. ncbi request reprint Morphologic and functional imaging of malignant pleural mesothelioma
    Masaki Yamamuro
    Department of Radiology and Surgery, Brigham and Women s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Eur J Radiol 64:356-66. 2007
    ..PET/CT seems to be superior to other imaging modalities in detecting more extensive disease involvement, and identifying unsuspected occult distant metastases...
  83. ncbi request reprint Multimodality treatment of diffuse malignant pleural mesothelioma
    Lambros S Zellos
    Department of Surgery, Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    Semin Oncol 29:41-50. 2002
    ..Randomized controlled studies comparing various strategies are lacking and, thus, the debate continues regarding the effectiveness of different treatment approaches...
  84. ncbi request reprint Assessment of malignant pleural mesothelioma with (18)F-FDG dual-head gamma-camera coincidence imaging: comparison with histopathology
    Victor H Gerbaudo
    Division of Nuclear Medicine, Department of Radiology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Nucl Med 43:1144-9. 2002
    ..The purpose of this study was to evaluate the usefulness of (18)F-FDG-CI in the assessment of malignant pleural mesothelioma using histopathology as the gold standard...
  85. pmc Metabolic significance of the pattern, intensity and kinetics of 18F-FDG uptake in malignant pleural mesothelioma
    V H Gerbaudo
    Division of Nuclear Medicine, Department of Radiology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Thorax 58:1077-82. 2003
    ..This pilot study evaluated the significance of the pattern, intensity and kinetics of 18F-FDG uptake in mesothelioma in the context of histopathology and surgical staging...
  86. ncbi request reprint Histone deacetylation is directly involved in desilencing the expression of the catalytic subunit of telomerase in normal lung fibroblast
    N K Mukhopadhyay
    Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Cell Mol Med 9:662-9. 2005
    ..Collectively, our study indicates that inhibition of histone deacetylation selectively regulates the transcriptional derepression of telomerase catalytic subunit in normal lung fibroblast cells compared to lung tumor cells...
  87. ncbi request reprint Unusual case of hemoptysis 13 years after bilobectomy
    Subroto Paul
    Division of Thoracic Surgery, Department of Surgery, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Ann Thorac Surg 83:1188-90. 2007
    ..Successful treatment required percutaneous embolization of the dominant bronchial collaterals, followed by completion pneumonectomy...
  88. ncbi request reprint Cardiac sarcoma 14 years after treatment for pleural mesothelioma
    Siyamek Neragi-Miandoab
    N Engl J Med 352:1929-30. 2005
  89. ncbi request reprint Activation of focal adhesion kinase in human lung cancer cells involves multiple and potentially parallel signaling events
    Nishit K Mukhopadhyay
    Division of Thoracic Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA
    J Cell Mol Med 9:387-97. 2005
    ..Collectively, this report defines the existence of multiple and potentially parallel Coll IV/beta1-integrin mediated signaling events in Calu-1 cells, which involve FAK, ERKs, and PKC...
  90. ncbi request reprint Non-small cell lung cancer
    David S Ettinger
    J Natl Compr Canc Netw 6:228-69. 2008
  91. doi request reprint Complications of extrapleural pneumonectomy
    Lambros Zellos
    Department of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    Semin Thorac Cardiovasc Surg 19:355-9. 2007
    ..We have drawn upon our single-institution experience to describe the most common source of morbidity following EPP and to offer successful interventions...
  92. pmc mTOR mediates survival signals in malignant mesothelioma grown as tumor fragment spheroids
    Shannon M Wilson
    Lung Biology Center, UCSF, San Francisco, CA 94143 0854, USA
    Am J Respir Cell Mol Biol 39:576-83. 2008
    ..We propose that mTOR mediates survival signals in many mesothelioma tumors. Inhibition of mTOR may provide a nontoxic adjunct to therapy directed against malignant mesothelioma, especially in those with high baseline expression of p-S6K...
  93. ncbi request reprint Video-assisted thoracic surgery lobectomy: report of CALGB 39802--a prospective, multi-institution feasibility study
    Scott J Swanson
    Surgery Committee of the Cancer and Leukemia Group B CALGB, Statistics Office of CALGB, and Respiratory Committee of CALGB, Chicago, IL, USA
    J Clin Oncol 25:4993-7. 2007
    ..To evaluate the technical feasibility and safety of video-assisted thoracic surgery (VATS) lobectomy for small lung cancers...
  94. ncbi request reprint Examination of a CpG island methylator phenotype and implications of methylation profiles in solid tumors
    Carmen J Marsit
    Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Cancer Res 66:10621-9. 2006
    ....
  95. ncbi request reprint Functional analysis of c-Met/hepatocyte growth factor pathway in malignant pleural mesothelioma
    Ramasamy Jagadeeswaran
    Section of Hematology Oncology, Department of Medicine, University of Chicago Cancer Research Center, University of Chicago Medical Center, Pritzker School of Medicine, Chicago, Illinois 60637, USA
    Cancer Res 66:352-61. 2006
    ..Ultimately, c-Met would be an important target for therapy against MPM...
  96. ncbi request reprint Diameter of non-small cell lung cancer correlates with long-term survival: implications for T stage
    Carlos M Mery
    Division of Thoracic Surgery and Department of Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Chest 128:3255-60. 2005
    ..To determine the effect of tumor diameter on the long-term survival of patients with stage I non-small cell lung cancer (NSCLC) within a large multi-institutional database, and to assess the accuracy of the T-descriptor threshold of 3 cm...
  97. ncbi request reprint Non-small cell lung cancer clinical practice guidelines in oncology
    David S Ettinger
    J Natl Compr Canc Netw 4:548-82. 2006
  98. ncbi request reprint Adenocarcinoma of the gastric cardia: what is the optimal surgical approach?
    Hiromichi Ito
    Department of Surgery, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Am Coll Surg 199:880-6. 2004
    ..The incidence of adenocarcinoma of the gastric cardia is rising in Western countries. This study evaluates prognostic factors associated with surgical management of this cancer...
  99. ncbi request reprint Esophageal cancer. Introduction
    David J Sugarbaker
    Harvard Medical School, Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    Semin Thorac Cardiovasc Surg 15:157. 2003
  100. ncbi request reprint Detection and quantification of SV40 large T-antigen DNA in mesothelioma tissues and cell lines
    Gavin J Gordon
    Division of Thoracic Surgery, Brigham and Women s Hospital, Boston, MA 02115, USA
    Oncol Rep 9:631-4. 2002
    ..In addition, SV40 sequences were found in 2/35 tissues and 3/7 cell lines in relatively low abundance. We conclude that SV40 is not a contributing factor in the pathobiology of the majority of MPM tumors from patients at our institution...
  101. ncbi request reprint Activating mutations of the noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia
    Mohamed Bentires-Alj
    Cancer Biology Program, Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
    Cancer Res 64:8816-20. 2004
    ..Our data demonstrate that mutations in PTPN11 occur at low frequency in several human cancers, especially neuroblastoma and AML, and suggest that Shp2 may be a novel target for antineoplastic therapy...

Research Grants1

  1. CANCER AND LEUKEMIA GROUP B
    David Sugarbaker; Fiscal Year: 2002
    ..Three stages of group development are described: (1) surgeon recruitment phase; (2) patient recruitment phase (educational activities about adjuvant therapy trials. etc.); and (3) protocol development phase (intellectual activities). ..