Bio

Clinical Focus


  • Pleural Diseases
  • Thymectomy
  • Bullectomy
  • Surgical Procedures, Minimally Invasive
  • Esophageal Cancer
  • Lung Volume Reduction
  • Thoracic Surgery, Video-Assisted
  • VATS
  • Sympathectomy
  • Emphysema Surgery
  • Mediastinal Cyst
  • Cancer > Thoracic Oncology
  • Thoracoscopy
  • Thymoma
  • Lung Cancer
  • sarcoma
  • Thoracic Surgery
  • Myasthenia Gravis
  • Thoracic Cancers - Thoracic Surgery
  • Pneumothorax
  • Mediastinal Diseases

Academic Appointments


Administrative Appointments


  • Physician Leader Thoracic Oncology DMG, Stanford Cancer Center (2010 - Present)
  • Chief, Stanford Division of Thoracic Surgery (2008 - Present)
  • Chief, Section of General Thoracic Surgery, UPenn (2003 - 2007)
  • Editorial Board Member, Annals of Thoracic Surgery (2001 - Present)
  • Member, AATS Workforce on Education (2008 - Present)
  • Member, STS Workforce on Evidence-based Surgery (2006 - Present)
  • Director, Stanford Respiratory Muscle Research Laboratory (2008 - Present)

Honors & Awards


  • Elected Member, American Surgical Association (2010)
  • Elected Member, Society of Clinical Surgery (2008)
  • "Top Doctors" Listing, “America’s Top Doctors” - peer elected (2007,08,09,10,11,12)
  • "Top Doctors" Listing, “America’s Top Doctors for Cancer -- peer-elected (2006,07,08 09 10 11 12)
  • Elected Member, American Association for Thoracic Surgery (2002)
  • “Top Docs” Listing, Philadelphia Magazine (2002, 2005, 2006, 2007)
  • Listed in Consumers’ Guide to Top Doctors, Center for the Study of Services (2001-2003)
  • Fellow, American College of Surgeons (2001)
  • Fellow, American College of Chest Physicians (2000)
  • 2nd Edward D. Churchill Research Scholarship, American Association for Thoracic Surgery (1999-2001)
  • National Research Service Award, National Institutes of Health (1990-1992)
  • William I Inouye Award for Excellence in Teaching, Department of Surgery, University of Pennsylvania Sch. of Med. (1991)
  • Cabot Graduation Prize, Harvard Medical School (1988)
  • Simpson Fellowship, (For study at Harvard Medical School) (1984-1988)
  • Havighurst Graduation Prize, Amherst College (Top History Thesis) (1984)
  • Manstein Graduation Prize, Amherst College (Top Premed Athlete) (1984)
  • Summa Cum Lauda, Amherst College (1984)
  • Phi Beta Kappa, Junior year induction, Amherst College (1983)

Professional Education


  • Medical Education:Harvard Medical School (1988) MA
  • Residency:Massachusetts General Hospital (1997) MA
  • Board Certification: Thoracic Surgery, American Board of Thoracic Surgery (1999)
  • Residency:Hospital of the University of Pennsylvania (1995) PA
  • Thoracic Surgery, Massachusetts General Hospital, Thoracic Surgery (1997)
  • Surgery Training, Hospital of the Univ of Penn, Surgery (1995)
  • MD, Harvard University, Medicine (1988)

Research & Scholarship

Current Research and Scholarly Interests


In clinical research, Dr. Shrager has been an innovator studying outcomes in a variety of areas within Thoracic Surgery including: parenchyma-sparing operations and minimally invasive resections for lung cancer, transcervical thymectomy for myasthenia gravis, and surgical treatment of emphysema.

In the lab, Dr. Shrager is focused on the impact of disease states upon the diaphragm. His group published the seminal paper (NEJM) describing diaphragm atrophy assoc'd with mechanical ventilation.

Clinical Trials


  • Three Different Radiation Therapy Regimens in Treating Patients With Limited-Stage Small Cell Lung Cancer Receiving Cisplatin and Etoposide Recruiting

    Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as etoposide and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which radiation therapy regimen is more effective when given together with chemotherapy in treating patients with limited-stage small cell lung cancer. This randomized phase III trial is comparing different chest radiation therapy regimens to see how well they work in treating patients with limited-stage small cell lung cancer.

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  • Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer Not Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which regimen of stereotactic body radiation therapy is more effective in treating patients with non-small cell lung cancer. PURPOSE: This randomized phase II trial is studying the side effects of two radiation therapy regimens and to see how well they work in treating patients with stage I non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact laura gable, (650) 736 - 0798.

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  • CyberKnife Radiosurgical Treatment of Inoperable Early Stage Non-Small Cell Lung Cancer Not Recruiting

    The purpose of this study is to assess the short and long-term outcomes after CyberKnife stereotactic radiosurgery for early stage non-small cell lung cancer (NSCLC) in patients who are medically inoperable.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

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  • 4D-CT-based Ventilation Imaging for Adaptive Functional Guidance in Radiotherapy Recruiting

    To determine the appropriate class of deformable image registration algorithm and metric best suited for four-dimensional (4D) CT-based ventilation assessment.

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  • Surgery With or Without Internal Radiation Therapy Compared With Stereotactic Body Radiation Therapy in Treating Patients With High-Risk Stage I Non-Small Cell Lung Cancer Not Recruiting

    RATIONALE: Surgery with or without internal radiation therapy may be an effective treatment for non-small cell lung cancer. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known whether stereotactic body radiation therapy is more effective than surgery with or without internal radiation therapy in treating non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying how well surgery with or without internal radiation therapy works compared with stereotactic body radiation therapy in treating patients with high-risk stage IA or stage IB non-small cell lung cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

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  • GSK1572932A Antigen-Specific Cancer Immunotherapeutic as Adjuvant Therapy in Patients With Non-Small Cell Lung Cancer Not Recruiting

    The purpose of this clinical trial is to demonstrate the benefit of the immunotherapeutic product GSK1572932A when given to patients with Non-Small Cell Lung Cancer, after removal of their tumor. A course of 13 injections will be administered over 27 months. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

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  • Microarray Analysis of Gene Expression and Identification of Progenitor Cells in Lung Carcinoma Recruiting

    This study will investigate gene expression profiles in normal human lung tissue, lung carcinoma and metastatic tumor to the lung. The expression of up to 20,000 genes in a given lung tissue sample will be examined by cDNA microarray analysis and compared to normal lung tissue. In addition, we hope to identify a particular subset of lung cancer cells with an enhanced capacity for proliferation and self-renewal , analogous to the stem cells recently identified for certain types of leukemia, breast cancer and brain tumors.

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  • Randomized Study to Compare CyberKnife to Surgical Resection In Stage I Non-small Cell Lung Cancer Not Recruiting

    Lung cancer remains the most frequent cause of cancer death in both men and women in the world. Surgical resection using lobectomy with mediastinal lymph node dissection or sampling has been a standard of care for operable early stage NSCLC. Several studies have reported high local control and survival using SBRT in stage I NSCLC patients. SBRT is now an accepted treatment for medically inoperable patients with stage I NSCLC and patients with operable stage I lung cancer are entered on clinical protocols. The purpose of this study is to conduct a phase III randomized study to compare CyberKnife SBRT with surgery, the current standard of care for stage I operable NSCLC.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lisa Zhou, (650) 736 - 4112.

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  • Imaging and Biomarkers of Hypoxia in Solid Tumors Recruiting

    To establish PET imaging with the tracer FMISO as an accurate and reliable method for measuring the oxygen content of a tumor and to establish the measurement of secreted markers in blood as an accurate and reliable method for measuring the oxygen content of a tumor.

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  • Pulmonary Interstitial Lymphography in Early Stage Lung Cancer Not Recruiting

    Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world. NSCLC annually causes 150,000 deaths in the US and greater than 1 million worldwide. The standard treatment for early stage NSCLC is lobectomy with lymphadenectomy. However, many patients are poor operative candidates or decline surgery. An emerging alternative is Stereotactic Body Radiation Therapy (SBRT). Mounting evidence from Phase I/II studies demonstrates that SBRT offers excellent local control. Most SBRT trials focused on small, peripheral tumors in inoperable patients. Increasingly, clinical trials study SBRT in operable patients, often with larger, central tumors. Using clinical staging, a significant proportion of patients harbor occult nodal metastases when undergoing SBRT to the primary tumor alone. Subgroups of patients carry even higher risk of nodal metastases. These nodal metastases frequently would be removed by surgical intervention. However, SBRT, at present, is only directed at the primary tumor, potentially leading to regional failures in otherwise curable patients. To increase the effectiveness of SBRT for lung tumors, the next logical step is to explore whether the highest risk areas of disease spread can be identified and targeted. Regional failure could be reduced and outcome improved in a significant proportion of patients treated with SBRT if the primary nodal drainage (PND) were identified, targeted and treated in addition to the primary tumor. We propose to conduct a study to determine how well water soluble iodinated contrast material when injected directly into the tumor can be visualized on CT scan and integrated into radiation therapy treatment planning.

    Stanford is currently not accepting patients for this trial. For more information, please contact Laura Gable, (650) 736 - 0798.

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  • Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients With Stage IIIA Non-Small Cell Lung Cancer (Cetuximab Closed as of 05/14/10) Recruiting

    RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without panitumumab in treating patients with non-small cell lung cancer. (cetuximab closed as of 05/14/10) PURPOSE: This randomized phase II trial is studying chemotherapy and radiation therapy to see how well they work when given with or without panitumumab in treating patients with stage IIIA non-small cell lung cancer. (cetuximab closed as of 05/14/10)

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Teaching

2013-14 Courses


Graduate and Fellowship Programs


Publications

Journal Articles


  • A Rare Population of CD24(+)ITGB4(+)Notch(hi) Cells Drives Tumor Propagation in NSCLC and Requires Notch3 for Self-Renewal CANCER CELL Zheng, Y., de la Cruz, C. C., Sayles, L. C., Alleyne-Chin, C., Vaka, D., Knaak, T. D., Bigos, M., Xu, Y., Hoang, C. D., Shrager, J. B., Fehling, H. J., French, D., Forrest, W., Jiang, Z., Carano, R. A., Barck, K. H., Jackson, E. L., Sweet-Cordero, E. A. 2013; 24 (1): 59-74

    Abstract

    Sustained tumor progression has been attributed to a distinct population of tumor-propagating cells (TPCs). To identify TPCs relevant to lung cancer pathogenesis, we investigated functional heterogeneity in tumor cells isolated from Kras-driven mouse models of non-small-cell lung cancer (NSCLC). CD24(+)ITGB4(+)Notch(hi) cells are capable of propagating tumor growth in both a clonogenic and an orthotopic serial transplantation assay. While all four Notch receptors mark TPCs, Notch3 plays a nonredundant role in tumor cell propagation in two mouse models and in human NSCLC. The TPC population is enriched after chemotherapy, and the gene signature of mouse TPCs correlates with poor prognosis in human NSCLC. The role of Notch3 in tumor propagation may provide a therapeutic target for NSCLC.

    View details for DOI 10.1016/j.ccr.2013.05.021

    View details for Web of Science ID 000321604000010

    View details for PubMedID 23845442

  • An Observational Study of Circulating Tumor Cells and F-18-FDG PET Uptake in Patients with Treatment-Naive Non-Small Cell Lung Cancer PLOS ONE Nair, V. S., Keu, K. V., Luttgen, M. S., Kolatkar, A., Vasanawala, M., Kuschner, W., Bethel, K., Iagaru, A. H., Hoh, C., Shrager, J. B., Loo, B. W., Bazhenova, L., Nieva, J., Gambhir, S. S., Kuhn, P. 2013; 8 (7)

    Abstract

    We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs"). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6) and median maximum standardized uptake value (SUVmax) was 7.2 (IQR 3.7-15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

    View details for DOI 10.1371/journal.pone.0067733

    View details for Web of Science ID 000321425300025

    View details for PubMedID 23861795

  • Approach to the patient with multiple lung nodules. Thoracic surgery clinics Shrager, J. B. 2013; 23 (2): 257-266

    Abstract

    It can be difficult to determine whether a patient with more than a single, "solid" lung nodule suspicious for malignancy is suffering from synchronous primary tumors or intrapulmonary metastasis. For this reason, if resection can be performed an aggressive approach is often warranted after demonstrating no mediastinal nodal disease. Increasing evidence suggests that the survival of a patient with a single, invasive lepidic-predominant adenocarcinoma depends on the stage of the invasive tumor, not on the presumed multiple in situ tumors. A suggested clinical approach to each of these types of multifocal tumors, solid and lepidic, is proposed in this article.

    View details for DOI 10.1016/j.thorsurg.2013.01.004

    View details for PubMedID 23566977

  • Diaphragm muscle atrophy in the mouse after long-term mechanical ventilation. Muscle & nerve Tang, H., Lee, M., Khuong, A., Wright, E., Shrager, J. B. 2013; 48 (2): 272-8

    Abstract

    Mechanical ventilation (MV) is a life-saving measure, but full ventilator support causes ventilator-induced diaphragm atrophy (VIDA). Previous studies of VIDA have relied on human biopsies or a rat model. If MV can induce diaphragm atrophy in mice, then mechanistic study of VIDA could be explored via genetic manipulation.We show that 18 hours of MV in mice results in a 15% loss of diaphragm weight and a 17% reduction in fiber cross-sectional area. Important catabolic cascades are activated in this mouse model: transcription of the ubiquitin ligases, atrogin and MuRF1, and the apoptotic marker, Bim, are increased; the marker of autophagy, LC3, is induced at the protein level and shows a punctate distribution in diaphragm muscle fibers.This mouse model recapitulates the key pathophysiological findings of other models of VIDA, and it will enable the genetic manipulation required to fully explore the mechanisms underlying this important process. Muscle Nerve, 48: 272-278, 2013.

    View details for PubMedID 23813537

  • Indications for Surgery in Patients with Localized Pulmonary Infection THORACIC SURGERY CLINICS Merritt, R. E., Shrager, J. B. 2012; 22 (3): 325-?

    Abstract

    Nowadays, antibiotic and antifungal therapy is effective in treating some of the infections that can involve the lung parenchyma in a localized manner, such as bacterial abscess and infection with nonresistant tuberculosis strains. However, other localized pulmonary infections, for example aspergilloma and mucormycosis, are highly resistant to nonsurgical therapy, and in these diseases there are no generally successful options that do not include surgical resection. This article reviews the indications for surgical intervention in the treatment of common infections involving the lung, and also focuses on the general approaches to their management.

    View details for DOI 10.1016/j.thorsurg.2012.05.005

    View details for Web of Science ID 000311863900007

    View details for PubMedID 22789596

  • Prognostic PET F-18-FDG Uptake Imaging Features Are Associated with Major Oncogenomic Alterations in Patients with Resected Non-Small Cell Lung Cancer CANCER RESEARCH Nair, V. S., Gevaert, O., Davidzon, G., Napel, S., Graves, E. E., Hoang, C. D., Shrager, J. B., Quon, A., Rubin, D. L., Plevritis, S. K. 2012; 72 (15): 3725-3734

    Abstract

    Although 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here, we analyzed 25 tumors from patients with NSCLCs to identify tumor PET-FDG uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and coexpressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived, and a prognostic model was identified in an external cohort and then tested in a validation cohort of patients with NSCLC. Four of eight single genes associated with FDG uptake (LY6E, RNF149, MCM6, and FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature [maximum standard uptake value (SUV(max)), SUV(variance), and SUV(PCA2)], each highly associated with survival in the external [HR, 5.87; confidence interval (CI), 2.49-13.8] and validation (HR, 6.12; CI, 1.08-34.8) cohorts, respectively. Cell-cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis.

    View details for DOI 10.1158/0008-5472.CAN-11-3943

    View details for Web of Science ID 000307354100004

    View details for PubMedID 22710433

  • Invited commentary. Annals of thoracic surgery Shrager, J. B. 2012; 94 (1): 240-?

    View details for DOI 10.1016/j.athoracsur.2012.04.029

    View details for PubMedID 22734987

  • Prophylaxis and Management of Atrial Fibrillation After General Thoracic Surgery THORACIC SURGERY CLINICS Merritt, R. E., Shrager, J. B. 2012; 22 (1): 13-?

    Abstract

    Atrial fibrillation (AF) commonly affects patients after general thoracic surgery. Postoperative AF increases hospital stay and charges. Effective prophylaxis and treatment is the goal. Calcium channel blockers prevent postoperative AF. Beta blockers are a less viable choice. Amiodarone prophylaxis should be avoided in patients with pulmonary dysfunction or who require pneumonectomy. In management of AF, a brief trial of rate-control agents is appropriate; however, chemical cardioversion with rhythm-control agents should be instituted after 24 hours. High-risk patients with history of stroke or transient ischemic attack, or with two or more risk factors for thromboembolism should receive anticoagulation therapy.

    View details for DOI 10.1016/j.thorsurg.2011.08.016

    View details for Web of Science ID 000311863600003

    View details for PubMedID 22108684

  • Invited commentary. Annals of thoracic surgery Shrager, J. B. 2011; 92 (6): 2005-2006

    View details for DOI 10.1016/j.athoracsur.2011.08.004

    View details for PubMedID 22115210

  • Morbidity and Mortality After Esophagectomy Following Neoadjuvant Chemoradiation ANNALS OF THORACIC SURGERY Merritt, R. E., Whyte, R. I., D'Arcy, N. T., Hoang, C. D., Shrager, J. B. 2011; 92 (6): 2034-2040

    Abstract

    Neoadjuvant chemoradiation (CRT) is an accepted treatment for locally advanced esophageal carcinoma. A survival benefit has not been definitively established, and there is concern that chemoradiation may increase postoperative morbidity and mortality.A retrospective review was made of 138 patients treated for esophageal carcinoma between January 1999 and December 2009. Fifty-four patients who underwent CRT followed by esophagectomy were compared with 84 patients who underwent esophagectomy alone.The chemoradiation and esophagectomy alone cohorts were well matched on all preoperative variables. There was a higher percentage of Ivor Lewis procedures in the esophagectomy alone cohort (82.0%) compared with the CRT cohort (59.3%; p = 0.006). Thirty-five percent of the CRT group underwent transhiatal esophagectomy. Thirty-day mortality was 6.0% (5 of 84) in the esophagectomy alone cohort compared with 1.9% (1 of 54) in the CRT cohort (p = 0.5). Similarly, mean intensive care unit stay (4.7 versus 6.5 days; p = 0.5), ventilator time (2.4 versus 4.2 days; p = 0.5), and length of stay (13.5 versus 17 days; p = 0.2) did not differ significantly between the groups. The overall major complication rates were similar in the CRT and esophagectomy alone cohorts: 57.4% versus 56% (p = 0.98). Multivariate analysis determined that coronary artery disease (p = 0.01; odds ratio 3.5) and transthoracic esophagectomy (p = 0.05; odds ratio 1.4) were predictive of development of postoperative complications. Only cervical anastomotic location (p = 0.04; odds ratio 3.0) was predictive of anastomotic leak on multivariate analysis.Neoadjuvant chemoradiation does not appear to increase postoperative morbidity or mortality after esophagectomy. Major postoperative complications are associated with the transthoracic approach and preoperative coronary artery disease.

    View details for DOI 10.1016/j.athoracsur.2011.05.121

    View details for Web of Science ID 000297333300023

    View details for PubMedID 21945223

  • Intrinsic apoptosis in mechanically ventilated human diaphragm: linkage to a novel Fos/FoxO1/Stat3-Bim axis FASEB JOURNAL Tang, H., Lee, M., Budak, M. T., Pietras, N., Hittinger, S., Vu, M., Khuong, A., Hoang, C. D., Hussain, S. N., Levine, S., Shrager, J. B. 2011; 25 (9): 2921-2936

    Abstract

    Mechanical ventilation (MV) is a life-saving measure in many critically ill patients. However, prolonged MV results in diaphragm dysfunction that contributes to the frequent difficulty in weaning patients from the ventilator. The molecular mechanisms underlying ventilator-induced diaphragm dysfunction (VIDD) remain poorly understood. We report here that MV induces myonuclear DNA fragmentation (3-fold increase; P<0.01) and selective activation of caspase 9 (P<0.05) and Bcl2-interacting mediator of cell death (Bim; 2- to 7-fold increase; P<0.05) in human diaphragm. MV also statistically significantly down-regulates mitochondrial gene expression and induces oxidative stress. In cultured muscle cells, we show that oxidative stress activates each of the catabolic pathways thought to underlie VIDD: apoptotic (P<0.05), proteasomal (P<0.05), and autophagic (P<0.01). Further, silencing Bim expression blocks (P<0.05) oxidative stress-induced apoptosis. Overlapping the gene expression profiles of MV human diaphragm and H?O?-treated muscle cells, we identify Fos, FoxO1, and Stat3 as regulators of Bim expression as well as of expression of the catabolic markers atrogin and LC3. We thus identify a novel Fos/FoxO1/Stat3-Bim intrinsic apoptotic pathway and establish the centrality of oxidative stress in the development of VIDD. This information may help in the design of specific drugs to prevent this condition.

    View details for DOI 10.1096/fj.11-183798

    View details for Web of Science ID 000294435200008

    View details for PubMedID 21597002

  • Benign emptying of the postpneumonectomy space. Annals of thoracic surgery Merritt, R. E., Reznik, S. I., DaSilva, M. C., Sugarbaker, D. J., Whyte, R. I., Donahue, D. M., Hoang, C. D., Smythe, W. R., Shrager, J. B. 2011; 92 (3): 1076-1081

    Abstract

    A fall in the postpneumonectomy fluid level is considered a sign of bronchopleural fistula (BPF) requiring surgical intervention. We have discovered however that in rare asymptomatic patients, this event may not require aggressive surgical treatment.After seeing a case of benign emptying of the postpneumonectomy space (BEPS), we surveyed 28 surgeons to determine its incidence and characteristics.Forty-four cases of BEPS were reported by 23 survey respondents. Among 7 fully documented cases from 4 institutions, we defined the following criteria: the patient must be asymptomatic (no fever, white cell count elevation, or fluid expectoration), negative culture results if fluid sampled (patient not receiving antibiotics), no BPF at bronchoscopy or ventilation scintigraphy scan (or both), and recovery without drainage, or retrospective assessment that the intervention was unnecessary. BEPS occurred between 5 days and 152 days after pneumonectomy (6 cases right pneumonectomy and 1 case left pneumonectomy). Four patients underwent no treatment, 1 patient underwent thoracoscopic exploration (sterile) and closure after antibiotic irrigation, 1 patient underwent thoracoscopic exploration alone, and 1 patient underwent open window thoracostomy (sterile) with eventual closure. In all 7 patients (except the patient who underwent the open window procedure) the space refilled within 8 weeks; no patient experienced a subsequent empyema/BPF. Four patients who met the initial criteria for BEPS went on to experience empyema. The incidence of BEPS appears related to pneumonectomy volume, particularly extrapleural pneumonectomy. Using surgeon volume assumptions, the incidence of BEPS is 0.65%.To our knowledge, BEPS is a previously unreported occurrence. We hypothesize that it results from postoperative intrapleural pressure shifts, with or without a microscopic BPF, that drive fluid out of the pleural space while failing to cause contamination. Awareness of BEPS' existence may allow surgeons to safely avoid open drainage procedures occasionally in patients who experience an asymptomatic fall in fluid level.

    View details for DOI 10.1016/j.athoracsur.2011.04.082

    View details for PubMedID 21871304

  • Tumor Volume as a Potential Imaging-Based Risk-Stratification Factor in Trimodality Therapy for Locally Advanced Non-small Cell Lung Cancer JOURNAL OF THORACIC ONCOLOGY Kozak, M. M., Murphy, J. D., Schipper, M. L., Donington, J. S., Zhou, L., Whyte, R. I., Shrager, J. B., Hoang, C. D., Bazan, J., Maxim, P. G., Graves, E. E., Diehn, M., Hara, W. Y., Quon, A., Quynh-Thu Le, Q. T., Wakelee, H. A., Loo, B. W. 2011; 6 (5): 920-926

    Abstract

    The role of trimodality therapy for locally advanced non-small cell lung cancer (NSCLC) continues to be defined. We hypothesized that imaging parameters on pre- and postradiation positron emission tomography (PET)-computed tomography (CT) imaging are prognostic for outcome after preoperative chemoradiotherapy (CRT)/resection/consolidation chemotherapy and could help risk-stratify patients in clinical trials.We enrolled 13 patients on a prospective clinical trial of trimodality therapy for resectable locally advanced NSCLC. PET-CT was acquired for radiation planning and after 45 Gy. Gross tumor volume (GTV) and standardized uptake value were measured at pre- and post-CRT time points and correlated with nodal pathologic complete response, loco-regional and/or distant progression, and overall survival. In addition, we evaluated the performance of automatic deformable image registration (ADIR) software for volumetric response assessment.All patients responded with average total GTV reductions after 45 Gy of 43% (range: 27-64%). Pre- and post-CRT GTVs were highly correlated (R² = 0.9), and their respective median values divided the patients into the same two groups. ADIR measurements agreed closely with manually segmented post-CRT GTVs. Patients with GTV ? median (137 ml pre-CRT and 67 ml post-CRT) had 3-year progression-free survival (PFS) of 14% versus 75% for GTV less than median, a significant difference (p = 0.049). Pre- and post-CRT PET-standardized uptake value did not correlate significantly with pathologic complete response, PFS, or overall survival.Preoperative CRT with carboplatin/docetaxel/45 Gy resulted in excellent response rates. In this exploratory analysis, pre- and post-CRT GTV predicted PFS in trimodality therapy, consistent with our earlier studies in a broader cohort of NSCLC. ADIR seems robust enough for volumetric response assessment in clinical trials.

    View details for DOI 10.1097/JTO.0b013e31821517db

    View details for Web of Science ID 000289554100012

    View details for PubMedID 21774104

  • Improved Survival after Pulmonary Metastasectomy for Soft Tissue Sarcoma JOURNAL OF THORACIC ONCOLOGY Predina, J. D., Puc, M. M., Bergey, M. R., Sonnad, S. S., Kucharczuk, J. C., Staddon, A., Kaiser, L. R., Shrager, J. B. 2011; 6 (5): 913-919

    Abstract

    Survival after pulmonary metastasectomy for soft tissue sarcoma (STS) has been lower than in osteosarcoma (14-40% versus 40-50%). With improved patient selection criteria and advanced chemotherapy agents, we hypothesized that survival after metastasectomy for STS has improved in recent years.Retrospective study of 48 patients undergoing pulmonary metastasectomy for STS between 1995 and 2007. Potential predictors of overall survival and disease-free survival (DFS) were examined using the log-rank test or Cox regression. Multivariate analysis was conducted using Cox regression.Overall survival after initial metastasectomy was 67% and 52% at 3 and 5 years, respectively; DFS was 17% and 10% at 3 and 5 years. Univariate analysis indicated that ?2 pulmonary metastases (p = 0.03), diameter of largest metastasis ?2 cm (p = 0.09), and the absence of extrapulmonary metastases (p = 0.10) were associated with longer overall survival. Absence of extrapulmonary metastases (p = 0.07) and smaller size of the largest pulmonary metastasis (p = 0.06) were associated with longer DFS. Before 2001, 46.7% of patients received adjuvant chemotherapy versus 72.7% after (p = 0.10). Neither use of chemotherapy nor chemotherapy type was related to overall survival or DFS.Five-year overall survival is substantially higher after pulmonary metastasectomy for STS in our study relative to previously published results (52% versus 14-40%). This improvement does not seem to be the result of greater use of, or newer, chemotherapeutic regimens. Among potential explanations, improved patient selection is the most likely factor.

    View details for DOI 10.1097/JTO.0b013e3182106f5c

    View details for Web of Science ID 000289554100011

    View details for PubMedID 21750417

  • Invited commentary. Annals of thoracic surgery Shrager, J. B. 2010; 90 (6): 1785-?

    View details for DOI 10.1016/j.athoracsur.2010.07.061

    View details for PubMedID 21095310

  • Evidence-based suggestions for management of air leaks. Thoracic surgery clinics Merritt, R. E., Singhal, S., Shrager, J. B. 2010; 20 (3): 435-448

    Abstract

    The management of postoperative alveolar air leaks (AALs) continues to challenge thoracic surgeons. AALs increase length of stay and health care costs, and likely lead to other postoperative complications. Staple line buttresses, topical sealants, pleural tents, pneumoperitoneum, and modifications of traditional chest tube management (ie, reduced suction) have all been proposed to help reduce AAL. However, the cost of some of the commercial products being marketed may outweigh their relative effectiveness, and some of these techniques and products have not been adequately studied to date. This article provides a review of the available evidence-based literature that addresses the efficacy of the options currently available to prevent and manage AALs. Management suggestions based on this literature are presented.

    View details for DOI 10.1016/j.thorsurg.2010.03.005

    View details for PubMedID 20619236

  • Early outcomes after bilateral thoracoscopy versus median sternotomy for lung volume reduction. Innovations (Philadelphia, Pa.) Puc, M. M., Sonnad, S. S., Shrager, J. B. 2010; 5 (2): 97-102

    Abstract

    : A National Emphysema Treatment Trial subanalysis, although finally describing outcomes as "comparable," suggested that bilateral lung volume reduction surgery (LVRS) by video-assisted thoracoscopic surgery (VATS) may be slightly less morbid than by median sternotomy (MS). We report a single surgeon experience using both the MS and VATS approaches to provide additional information on this issue in a setting of uniform patient selection and perioperative management. Our hypothesis was that a VATS approach would provide equivalent or less morbidity than MS despite being applied to a group of patients subjectively selected to be higher risk than those undergoing MS.: Consecutive patients over a 9-year period underwent LVRS by one surgeon by either MS or VATS in a nonrandomized fashion. Thoracoscopy was selected over MS primarily when the surgeon estimated a greater overall risk profile and thus a greater chance of morbidity/mortality in a particular patient.: There were 15 patients in the VATS group and 35 in the MS group. In terms of measures of risk profile, there were no differences between the groups that met statistical significance, but several values trended toward higher risk within the VATS group (eg, age, 63 VATS vs. 59 MS, P = 0.08; moderate pulmonary hypertension, 38% VATS vs. 14% MS, P = 0.11; and residual volume, 241% VATS vs. 226% MS, P = 0.32). With regard to outcomes, operative time was significantly longer in the VATS group (VATS = 155 minutes vs. MS=129 minutes, P = 0.01). All other outcomes, including the incidence of major complications (13.3% VATS vs. 17.1% MS, P = 0.39), were similar between the groups. There was a single death within 90 days (1.9% of entire series; 2.9% of MS group).: In this series, although patients undergoing LVRS by VATS tended to have a higher risk profile, their outcomes were no worse than in those undergoing LVRS by MS. This suggests that the VATS approach to bilateral LVRS may incur slightly less morbidity and thus may be the best option in the most compromised patients who is nonetheless felt will benefit from LVRS.

    View details for DOI 10.1097/IMI.0b013e3181d9277d

    View details for PubMedID 22437355

  • Intraoperative and postoperative management of air leaks in patients with emphysema. Thoracic surgery clinics Shrager, J. B., DeCamp, M. M., Murthy, S. C. 2009; 19 (2): 223-?

    Abstract

    Air leaks after pulmonary surgery represent a substantial clinical problem. When they persist beyond a few days, air leaks appear to increase complications and costs. Clearly, emphysema patients are those at greatest risk for developing problematic air leaks. This article, after reviewing what is known about the epidemiology and clinical significance of air leaks, discusses the various techniques that may be employed to avoid the development of problematic air leaks and to manage them when they do occur. It reviews the data available on newer and more traditional options for the prophylaxis and management of air leaks and offers the authors' opinions about the optimal approaches in various clinical situations.

    View details for DOI 10.1016/j.thorsurg.2009.02.004

    View details for PubMedID 19662965

  • Thymoma ANNALS OF THORACIC SURGERY Shrager, J. B. 2009; 87 (1): 339-341
  • Thoracoscopic total parietal pleurectomy for primary spontaneous pneumothorax ANNALS OF THORACIC SURGERY Nathan, D. P., Taylor, N. E., Low, D. W., Raymond, D., Shrager, J. B. 2008; 85 (5): 1825-1827

    Abstract

    Although the management of spontaneous pneumothorax through a thoracotomy traditionally included apical pleurectomy, thoracoscopic treatment of this problem does not generally include pleurectomy. Thoracoscopy in fact allows excellent exposure to perform total parietal pleurectomy, and we hypothesize that including total pleurectomy will reduce recurrences. We describe here the technique of thoracoscopic total parietal pleurectomy and the early outcomes afterward.

    View details for DOI 10.1016/j.athoracsur.2007.11.043

    View details for Web of Science ID 000255319900064

    View details for PubMedID 18442607

  • Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans NEW ENGLAND JOURNAL OF MEDICINE Levine, S., Nguyen, T., Taylor, N., Friscia, M. E., Budak, M. T., Rothenberg, P., Zhu, J., Sachdeva, R., Sonnad, S., Kaiser, L. R., Rubinstein, N. A., Powers, S. K., Shrager, J. B. 2008; 358 (13): 1327-1335

    Abstract

    The combination of complete diaphragm inactivity and mechanical ventilation (for more than 18 hours) elicits disuse atrophy of myofibers in animals. We hypothesized that the same may also occur in the human diaphragm.We obtained biopsy specimens from the costal diaphragms of 14 brain-dead organ donors before organ harvest (case subjects) and compared them with intraoperative biopsy specimens from the diaphragms of 8 patients who were undergoing surgery for either benign lesions or localized lung cancer (control subjects). Case subjects had diaphragmatic inactivity and underwent mechanical ventilation for 18 to 69 hours; among control subjects diaphragmatic inactivity and mechanical ventilation were limited to 2 to 3 hours. We carried out histologic, biochemical, and gene-expression studies on these specimens.As compared with diaphragm-biopsy specimens from controls, specimens from case subjects showed decreased cross-sectional areas of slow-twitch and fast-twitch fibers of 57% (P=0.001) and 53% (P=0.01), respectively, decreased glutathione concentration of 23% (P=0.01), increased active caspase-3 expression of 100% (P=0.05), a 200% higher ratio of atrogin-1 messenger RNA (mRNA) transcripts to MBD4 (a housekeeping gene) (P=0.002), and a 590% higher ratio of MuRF-1 mRNA transcripts to MBD4 (P=0.001).The combination of 18 to 69 hours of complete diaphragmatic inactivity and mechanical ventilation results in marked atrophy of human diaphragm myofibers. These findings are consistent with increased diaphragmatic proteolysis during inactivity.

    View details for Web of Science ID 000254308400003

    View details for PubMedID 18367735

  • Early changes of lung function and structure in an elastase model of emphysema - a hyperpolarized He-3 MRI study JOURNAL OF APPLIED PHYSIOLOGY Emami, K., Cadman, R. V., Woodburn, J. M., Fischer, M. C., Kadlecek, S. J., Zhu, J., Pickup, S., Guyer, R. A., Law, M., Vahdat, V., Friscia, M. E., Ishii, M., Yu, J., Gefter, W. B., Shrager, J. B., Rizi, R. R. 2008; 104 (3): 773-786

    Abstract

    Early changes of lung function and structure were studied in the presence of an elastase-induced model of emphysema in 35 Sprague-Dawley rats at mild (5 U/100 g) and moderate (10 U/100 g) severities. Lung ventilation was measured on a regional basis (at a planar resolution of 3.2 mm) by hyperpolarized 3He MRI at 5 and 10 wk after model induction. Subsequent to imaging, average alveolar diameter was measured from histological slices taken from the centers of each lobe. Changes of mean fractional ventilation, mean linear intercept, and intrasubject heterogeneity of ventilation were studied during disease progression. Mean fractional ventilation was significantly different between healthy controls (0.23 +/- 0.04) and emphysematous animals at both time points in the 10-unit group (0.06 +/- 0.02 and 0.12 +/- 0.05, respectively). Changes in average alveolar diameter were not statistically observable until the 10th wk between healthy (37 +/- 10 microm) and emphysematous rats (73 +/- 25 and 95 +/- 31 microm, for 5 and 10 units, respectively). Assessment of function-structure correlation suggested that the majority of the decline in fractional ventilation occurred in the first 5 wk, while enlargement of alveolar diameters appeared primarily between the 5th and 10th wk. A thresholding metric, based on the 20th percentile of fractional ventilation over the entire lung, was utilized to detect the onset of the disease with confidence, independent of whether the regional ventilation measurements were normalized with respect to the delivered tidal volume and estimated functional residual capacity of each individual rat.

    View details for DOI 10.1152/japplphysiol.00482.2007

    View details for Web of Science ID 000253822900028

    View details for PubMedID 18063806

  • Extended transcervical thymectomy in the treatment of myasthenia gravis MYASTHENIA GRAVIS AND RELATED DISORDERS: 11TH INTERNATIONAL CONFERENCE Khicha, S. G., Kaiser, L. R., Shrager, J. B. 2008; 1132: 336-343

    Abstract

    The ideal operative technique for thymectomy in myasthenia gravis remains controversial. Most surgeons perform thymectomy via median sternotomy, some supplementing this with an even more extensive mediastinal and cervical dissection designed to remove all areas of possible ectopic thymic tissue. We and others have advocated a transcervical approach that is less morbid and costly than sternotomy approaches. The transcervical approach allows a complete extracapsular thymic resection, but it does not address all areas of potential ectopic thymic tissue. We have published our experience with 151 extended transcervical thymectomies (TCT). At mean follow-up of 53 months (complete follow-up in 97%), Kaplan-Meier estimates of complete stable remission were 33% and 35% at 3 and 6 years. If one includes patients who became asymptomatic but remained on low dose, single-drug immunosuppression as complete remissions (CRs), then the CR rates were 43% and 45% at 3 and 6 years. Longer term (mean 83 months) follow-up of the earliest 84 patients in the series showed preserved CR rates. On multivariate analysis, only preoperative Osserman Class (group mean 2.3) was significantly associated with improved CR rate. These results were obtained with a major operative complication rate of 0.7% and minor complication rate of 6.6%, and nearly every operation was performed without the need for overnight hospital admission. We believe that these response rates following TCT are sufficiently similar to those following transsternal techniques of thymectomy to allow us to recommend this less morbid and less costly operation as an eminently reasonable choice in the surgical treatment of myasthenia gravis.

    View details for DOI 10.1196/annals.1405.006

    View details for Web of Science ID 000257139900041

    View details for PubMedID 18567885

  • Complications of video-assisted thoracoscopic lung biopsy in patients with interstitial lung disease ANNALS OF THORACIC SURGERY Kreider, M. E., Hansen-Flaschen, J., Ahmad, N. N., Rossman, M. D., Kaiser, L. R., Kucharczuk, J. C., Shrager, J. B. 2007; 83 (3): 1140-1145

    Abstract

    Current guidelines recommend surgical lung biopsy for diagnosis of interstitial lung diseases (ILDs) in selected patients. To shed light on the risk-benefit ratio for this recommendation, we examined the morbidity and mortality associated with video-assisted thoracoscopic surgical (VATS) lung biopsy in a group of outpatients.A retrospective cohort study was conducted of 68 consecutive ambulatory patients with radiographically apparent interstitial lung disease (ILD) referred for VATS biopsy during a 6-year period. Incidence of postoperative mortality, prolonged air leaks, pneumonias, and re-admissions were calculated. Risk factors for complications of surgery were examined.Three deaths occurred within 60 days after biopsy for a mortality rate of 4.4% (95% confidence interval [CI], 1% to 12%), and 19.1% (95% CI, 11% to 31%) experienced one or more complications of surgery. Risk factors for morbidity included preoperative dependence on oxygen therapy and pulmonary hypertension. The three patients who died had usual interstitial pneumonia on their biopsy specimen and were reintubated postoperatively for acute lung injury. Aggregation of articles published over the past 10 years reporting on surgical lung biopsy for the diagnosis of ILD yielded a postoperative mortality rate of 2% to 4.5%.VATS lung biopsy for diagnosis of ILD, even in ambulatory patients, is not an entirely benign procedure. Biopsy rarely may trigger an acute exacerbation of usual interstitial pneumonitis. The risk of postoperative complications appears to be greatest in those dependent on oxygen and those who have pulmonary hypertension. This information may be used in weighing the risk-benefit ratio of biopsy in individual patients.

    View details for DOI 10.1016/j.athoracsur.2006.10.002

    View details for Web of Science ID 000244648100037

    View details for PubMedID 17307476

  • Cytokine response is lower after lung volume reduction through bilateral thoracoscopy versus sternotomy ANNALS OF THORACIC SURGERY Friscia, M. E., Zhu, J., Kolff, J. W., Chen, Z., Kaiser, L. R., Deutschman, C. S., Shrager, J. B. 2007; 83 (1): 252-256

    Abstract

    Lung volume reduction surgery performed through bilateral video-assisted thoracoscopy (BVATS) was associated in the National Emphysema Treatment Trial with a statistically significant reduction in intensive care unit days, failure to wean, hospital stay, and cost, and earlier recovery compared with median sternotomy. Studies comparing other minimally invasive techniques with "open" procedures, including pulmonary lobectomy, have demonstrated reduced serum proinflammatory mediators postoperatively. We measured these levels after lung volume reduction surgery through BVATS and sternotomy.Serum cytokine levels were measured by radioimmunoassay in 9 consecutive, steroid-free patients undergoing sternotomy and lung volume reduction surgery and 6 undergoing BVATS and lung volume reduction surgery. The groups were not statistically different with respect to age, partial pressure of arterial carbon dioxide, percent forced expiratory volume in 1 second, percent residual volume, percent total lung capacity, diffusion capacity of the lung for carbon monoxide, 6-minute walk, or apical perfusion fraction. Proinflammatory interleukin 6 and interleukin 8 and antiinflammatory interleukin 10 were evaluated preoperatively and postoperatively on days 1, 4, and 5. Clinical data were prospectively collected.There were no major postoperative complications or deaths. Interleukin 6 levels were lower in the BVATS than the sternotomy group (p = 0.016 by repeated measures analysis of variance). Interleukin 8 levels were lower in the BVATS group at most postoperative time points, but there were no significant differences in interleukin 8 or interleukin 10 levels between the sternotomy and BVATS groups at any individual time point or by analysis of variance.Use of a BVATS approach to lung volume reduction surgery is associated with reduced postoperative release of proinflammatory cytokines compared with a sternotomy approach. This may account for the reduction in recovery time and some measures of postoperative morbidity seen with the BVATS approach.

    View details for DOI 10.1016/j.athoracsur.2006.08.012

    View details for Web of Science ID 000242963400041

    View details for PubMedID 17184673

  • Parasternal intercostal muscle remodeling in severe chronic obstructive pulmonary disease JOURNAL OF APPLIED PHYSIOLOGY Levine, S., Nguyen, T., Friscia, M., Zhu, J., Szeto, W., Kucharczuk, J. C., Tikunov, B. A., Rubinstein, N. A., Kaiser, L. R., Shrager, J. B. 2006; 101 (5): 1297-1302

    Abstract

    Studies in experimental animals indicate that chronic increases in neural drive to limb muscles elicit a fast-to-slow transformation of fiber-type proportions and myofibrillar proteins. Since neural drive to the parasternal intercostal muscles (parasternals) is chronically increased in patients with severe chronic obstructive pulmonary diseases (COPDs), we carried out the present study to test the hypothesis that the parasternals of COPD patients exhibit an increase in the proportions of both slow fibers and slow myosin heavy chains (MHCs). Accordingly, we obtained full thickness parasternal muscle biopsies from the third interspace of seven COPD patients (mean +/- SE age: 59 +/- 4 yr) and seven age-matched controls (AMCs). Fiber typing was done by immunohistochemistry, and MHC proportions were determined by SDS-PAGE followed by densitometry. COPD patients exhibited higher proportions of slow fibers than AMCs (73 +/- 4 vs. 51 +/- 3%; P < 0.01). Additionally, COPD patients exhibited higher proportions of slow MHC than AMCs (56 +/- 4 vs. 46 +/- 4%, P < 0.04). We conclude that the parasternal muscles of patients with severe COPD exhibit a fast-to-slow transformation in both fiber-type and MHC proportions. Previous workers have demonstrated that remodeling of the external intercostals, another rib cage inspiratory muscle, elicited by severe COPD is characterized by a slow-to-fast transformation in both fiber types and MHC isoform proportions. The physiological significance of this difference in remodeling between these two inspiratory rib cage muscles remains to be elucidated.

    View details for DOI 10.1152/japplphysiol.01607.2005

    View details for Web of Science ID 000242159300007

    View details for PubMedID 16777998

  • Outcomes after 151 extended transcervical thymectomies for myasthenia gravis ANNALS OF THORACIC SURGERY Shrager, J. B., Nathan, D., Brinster, C. J., Yousuf, O., Spence, A., Chen, Z., Kaiser, L. R. 2006; 82 (5): 1863-1869

    Abstract

    The ideal operative technique for thymectomy in myasthenia gravis (MG) remains controversial. We present the largest series of extended transcervical thymectomy to provide outcomes data to compare with transsternal procedures.A retrospective chart review/interview was made of 164 patients operated upon from 1992 to 2004. Complete remission (CR) was defined as asymptomatic off medication for 6 months or asymptomatic on low-dose single-drug therapy (< or = 10 mg/d prednisone or < or = 150 mg/d azathioprine). A modified Osserman classification based upon the Myasthenia Gravis Foundation of America quantitative disease severity score was employed.The overall complication rate was 7.3%, and nearly all procedures were outpatient. Mean age at surgery was 43 years, and mean preoperative Osserman class was 2.3 (21% class 1; 39% class 2; 28% class 3; 12% class 4). Mean length of follow-up was 53 months. Mean postoperative Osserman class was 1.0. Nineteen percent of patients failed to improve. The crude cumulative CR rate was 37% (n = 58). Kaplan-Meier estimates of CR were 43% and 45% at 3 and 6 years, respectively. On multivariate analysis, only preoperative disease severity was significantly (inversely) associated with Kaplan-Meier CR rates. Longer-term follow-up (83 months) of only the earlier patients shows preserved CR rates (46%).This largest series of extended transcervical thymectomy for MG confirms that the 5-year Kaplan-Meier CR rate is comparable with that obtained after transsternal procedures. Patients with less severe disease have higher CR rates. Complete responses are durable, as the CR rate remains stable with extended follow-up.

    View details for DOI 10.1016/j.athoracsur.2006.05.110

    View details for Web of Science ID 000241497600044

    View details for PubMedID 17062262

  • Anterior surgical approaches to the thoracic outlet JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Marshall, M. B., Kucharczuk, J. C., Shrager, J. B., Kaiser, L. R. 2006; 131 (6): 1255-1260

    Abstract

    The anatomy of the thoracic outlet is complex, and the optimum surgical approach to pathologic disease at this location is controversial. Although the Dartevelle approach to the apex seems to be a safer and more direct approach, this technique has not been widely adopted in the United States. We have used this approach for pathologic disease at the thoracic outlet and modified it. Our experience is described in this article.A retrospective review was performed on all patients who underwent an anterior approach between December 1997 and May 2003.There were 42 patients who underwent anterior approaches to pathologic disease at the level of the outlet. Diagnosis included apical non-small cell lung cancers (20 patients), osteosarcoma (2 patients), spinal cord compression (5 patients), solitary metastasis (4 patients), and benign lesions (11 patients). There were 22 female and 20 male patients with ages ranging from 26 to 82 years (mean age, 54.6 years). There were 25 complications in 14 patients and 1 in-hospital death. A transmanubrial approach was used in 14 patients, the standard Dartevelle technique was used in 8 patients, and a transclavicular approach with reapproximation of the clavicle was used in 20 patients. Reapproximation failed in 5 patients (3/3 patients who underwent fixation with mini-plates and 2/17 patients with sternal wires).The anterior approach is a useful adjunct to a thoracic surgeon's armamentarium. When a transclavicular approach is optimal, division and reapproximation of the clavicle are feasible. In our experience, reapproximation with wires is superior to plates and screws.

    View details for DOI 10.1016/j.jtcvs.2006.01.044

    View details for Web of Science ID 000238023300011

    View details for PubMedID 16733154

  • Invited commentary. Annals of thoracic surgery Shrager, J. B. 2006; 81 (1): 334-?

    View details for PubMedID 16368395

  • Comparative study of subxiphoid versus video-thoracoscopic pericardial "'window" ANNALS OF THORACIC SURGERY O'Brien, P. K., Kucharczuk, J. C., Marshall, M. B., Friedberg, J. S., Chen, Z., Kaiser, L. R., Shrager, J. B. 2005; 80 (6): 2013-2019

    Abstract

    It remains undefined whether surgical subxiphoid drainage or thoracoscopic pericardial "window" is the optimal operative approach to pericardial effusion. We hypothesized that the true window into the pleural space created by the latter might improve the duration of freedom from recurrent effusion.We conducted a retrospective chart review of indications, preoperative and intraoperative variables, morbidity, recurrence, and survival.Fifty-six patients underwent the subxiphoid procedure and 15 underwent the thoracoscopic procedure. Echocardiographic evidence of tamponade was present before 8 of 10 thoracoscopic procedures (80%) and 43 of 56 subxiphoid procedures (81%) for which descriptions of hemodynamics were available. In addition, non-pericardial procedures were performed in 10 (67%) and 18 (32%) patients, respectively (p = 0.020). Anesthesia time was longer at thoracoscopy (117.1 +/- 32.4 vs 81.1 +/- 25.5 minutes; p < 0.001). Procedural morbidity was higher after thoracoscopy (4 [27%] vs 1 [2%]; p = 0.006), but was generally minor. Hospital mortality tended to be higher after the subxiphoid procedure (7 [13%] vs 0 [0%]; p = 0.332), but none of the deaths was procedure-related. Follow-up was complete for 65 patients (92%). Recurrence occurred in 1 thoracoscopy patient (8%) and 5 subxiphoid patients (10%) (p = 1.000). Mean time to recurrence by Kaplan-Meier analysis trends were longer after thoracoscopy (36.1 vs 11.4 months; p = 0.16), and multivariate analysis identified the thoracoscopic approach as an independent predictor of freedom from recurrence (relative risk, 0.41; p = 0.014).Operative time and minor procedural morbidity are higher with thoracoscopic pericardial window, but long-term control of effusion seemed to be better than after subxiphoid surgical drainage.

    View details for Web of Science ID 000233926800006

    View details for PubMedID 16305836

  • Pain and physical function are similar following axillary, muscle-sparing vs posterolateral thoracotomy CHEST Ochroch, E. A., Gottschalk, A., Augoustides, J. G., Aukburg, S. J., Kaiser, L. R., Shrager, J. B. 2005; 128 (4): 2664-2670

    Abstract

    We set out to determine whether there is a difference in postoperative pain and recovery after the patient undergoes the axillary muscle-sparing incision (ie, muscle-sparing thoracotomy [MT]) vs the modified posterolateral incision (ie, posterolateral thoracotomy [PT]).Analysis of a database originally collected to determine the effect of the timing of epidural analgesia on long-term outcome after thoracotomy.The Hospital of the University of Pennsylvania.Patients presenting for lobectomy, segmentectomy, or bilobectomy.Pain, physical activity, and the extent that pain interfered with activities following major thoracotomy were prospectively assessed with standard questionnaires (ie, the brief pain inventory and the Medical Outcomes Study 36-item short form) on postoperative days 1 to 5, and at postoperative weeks 4, 8, 12, 24, 36, and 48 by a blinded research assistant. Perioperative care was standardized and included patient-controlled thoracic epidural analgesia until thoracostomy tube removal.Eighty-two subjects underwent MT and 38 subjects underwent PT during the 16-month accrual period. There were no significant differences in demographics. Pain reported during hospitalization and after hospital discharge did not differ with respect to incision type (p > or = 0.17). Postoperative physical activity levels were significantly less than those reported preoperatively, with a trend toward better functioning in the MT groups after 8 weeks. Incision type did not predict complications, morbidity, or mortality.When comparing patients who had undergone vertical, axillary, wholly MT to those who had undergone modified serratus muscle-sparing PT, postoperative differences in pain were not apparent. One should not anticipate reduced pain or more rapid overall recovery following MT, at least when epidural analgesia is used aggressively for perioperative pain control.

    View details for Web of Science ID 000232679400112

    View details for PubMedID 16236940

  • Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm JOURNAL OF APPLIED PHYSIOLOGY Nguyen, T., Rubinstein, N. A., Vijayasarathy, C., Rome, L. C., Kaiser, L. R., Shrager, J. B., Levine, S. 2005; 98 (6): 2004-2010

    Abstract

    We have previously demonstrated that human diaphragm remodeling elicited by severe chronic obstructive pulmonary disease (COPD) is characterized by a fast-to-slow myosin heavy chain isoform transformation. To test the hypothesis that COPD-induced diaphragm remodeling also elicits a fast-to-slow isoform shift in the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), the other major ATPase in skeletal muscle, we obtained intraoperative biopsies of the costal diaphragm from 10 severe COPD patients and 10 control subjects. We then used isoform-specific monoclonal antibodies to characterize diaphragm fibers with respect to the expression of SERCA isoforms. Compared with control diaphragms, COPD diaphragms exhibited a 63% decrease in fibers expressing only fast SERCA (i.e., SERCA1; P < 0.001), a 190% increase in fibers containing both fast and slow SERCA isoforms (P < 0.01), and a 19% increase (P < 0.05) in fibers expressing only the slow SERCA isoform (i.e., SERCA2). Additionally, immunoblot experiments carried out on diaphragm homogenates indicated that COPD diaphragms expressed only one-third the SERCA1 content noted in control diaphragms; in contrast, COPD and control diaphragms did not differ with respect to SERCA2 content. The combination of these histological and immunoblot results is consistent with the hypothesis that diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow SERCA isoform transformation. Moreover, the combination of these SERCA data and our previously reported myosin heavy chain isoform data (Levine S, Nguyen T, Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, and Shrager JB. Am J Respir Crit Care Med 168: 706-713, 2003) suggests that diaphragm remodeling elicited by severe COPD should decrease ATP utilization by the diaphragm.

    View details for DOI 10.1152/japplphysiol.00767.2004

    View details for Web of Science ID 000229365500006

    View details for PubMedID 15718407

  • Which patients with stage III non-small cell lung cancer should undergo surgical resection? ONCOLOGIST Patel, V., Shrager, J. B. 2005; 10 (5): 335-344

    Abstract

    The treatment of patients with stage III NSCLC remains controversial. Stage III NSCLC comprises a fairly heterogeneous group of tumors, and furthermore only sparse data from randomized clinical trials exist to guide therapy decisions. This review article proposes a management algorithm for patients with stage III NSCLC that is based upon the currently available data on surgical therapy, chemotherapy, and radiation therapy. By necessity, given the paucity of strong data, a good deal of opinion is offered. The choice to proceed with aggressive, combined modality treatment is presented in light of extent of local disease as well as patient performance status.

    View details for Web of Science ID 000229026000014

    View details for PubMedID 15851792

  • Catamenial pneumothorax: optimal hormonal and surgical management EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Marshall, M. B., Ahmed, Z., Kucharczuk, J. C., Kaiser, L. R., Shrager, J. B. 2005; 27 (4): 662-666

    Abstract

    To provide further information addressing the etiology, optimal hormonal management and surgical management in catamenial pneumothorax (CP).We retrospectively analyzed records of all female patients operated on for spontaneous pneumothorax at a university hospital between January 1993 and March 2002.In eight of 24 patients, pneumothoraces were timed with menses. In all, the right side was involved. Seven patients were on hormonal medications pre-operatively and six post-operatively. All six patients taking estrogen/progesterone replacement had recurrences pre-operatively and two of three had recurrences post-operatively while on these medications. No patient suffered a pneumothorax either pre- or post-operatively while taking a gonadotropin releasing hormone agonist (two and three patients, respectively). Intraoperative findings included diaphragmatic implants [5] diaphragmatic fenestrations [4], apical blebs [2] and visceral pleural implants [2]. All pathology was specifically addressed at the time of surgery. Pleural space management included mechanical pleurodesis in seven and pleurectomy with talc insufflation in 1. Follow-up ranged from 27 to 63 months with a mean of 48 months. Three patients developed post-operative recurrences. One was managed without intervention and two required additional procedures.Catamenial pneumothorax is under appreciated, representing up to one-third of women with spontaneous pneumothorax. Hormonal agents that allow for menses are ineffective. Gonadotropin releasing hormone agonists should be considered as part of the pre-operative or post-operative management in high risk patients. Our findings suggest that an additional intervention to augment pleural symphysis at the level of the diaphragm should be performed.

    View details for DOI 10.1016/j.ejcts.2004.12.047

    View details for Web of Science ID 000228319600035

    View details for PubMedID 15784370

  • Hyperpolarized helium-3 MR imaging of pulmonary function RADIOLOGIC CLINICS OF NORTH AMERICA Ishii, M., Fischer, M. C., Emami, K., Alavi, A., Spector, Z. Z., Yu, J. S., Baumgartner, J. E., Itkin, M., Kadlecek, S. J., Zhu, J. L., Bono, M., Gefter, W. B., Lipson, D. A., Shrager, J. B., Rizi, R. R. 2005; 43 (1): 235-?

    Abstract

    Recent advances in HP MR imaging contrast agents have led to novel tests of pulmonary function. Many of these tests show promise in the clinical arena.

    View details for DOI 10.1016/j.rcl.2004.09.010

    View details for Web of Science ID 000225875500017

    View details for PubMedID 15693659

  • Lung cancer in transplant recipients - A single-institution experience ARCHIVES OF SURGERY Ahmed, Z., Marshall, M. B., Kucharczuk, J. C., Kaiser, L. R., Shrager, J. B. 2004; 139 (8): 902-906

    Abstract

    That aggressive surgical treatment of lung cancer (LC) is justified by stage-based outcome in immunosuppressed solid organ transplant recipients.Case series.University hospital.Lung cancer developed in 15 patients (0.28%) among a solid organ transplant recipient population of 5400 accrued at our institution over a 25-year period.Smoking prevalence, subtypes and stages of LC represented, operative morbidity, and survival.The mean time from transplantation to the diagnosis of LC was 76 months (range, 9-192 months). Eight patients received kidneys; 3, lungs; and 4, hearts. Only 11 patients (73%) had a smoking history (mean, 66 pack-years). The following carcinomas developed in our patient population: adenocarcinoma, 6 patients; squamous cell, 5; large cell undifferentiated, 2; bronchoalveolar, 1; and small cell, 1. Eight patients (53%) presented with inoperable stage IIIB or IV disease. The remaining patients presented in stages IA (n = 2), IB (n = 1), IIB (n = 2), and IIIA (n = 2); all underwent resection. No major postoperative complications occurred. All patients with stage IIIB or greater disease with or without treatment died quickly (mean survival, 1.4 months; range, 0.33-3.0 months). All patients with stage IIB or less remain alive a mean of 37 months after resection. Patients with stage IIIA survived only a mean of 6.0 months despite resection.Regarding LCs in transplant recipients compared with LCs in the nontransplant population, we find that (1) there is an increased incidence among nonsmokers; (2) death occurs rapidly in unresected patients; (3) resection carries a low morbidity rate; and (4) resection seems to offer a high chance of cure in those with cancers staged IIB or less.

    View details for Web of Science ID 000223118400024

    View details for PubMedID 15302702

  • Myosin gene mutation correlates with anatomical changes in the human lineage NATURE Stedman, H. H., Kozyak, B. W., Nelson, A., Thesier, D. M., Su, L. T., Low, D. W., Bridges, C. R., Shrager, J. B., Minugh-Purvis, N., Mitchell, M. A. 2004; 428 (6981): 415-418

    Abstract

    Powerful masticatory muscles are found in most primates, including chimpanzees and gorillas, and were part of a prominent adaptation of Australopithecus and Paranthropus, extinct genera of the family Hominidae. In contrast, masticatory muscles are considerably smaller in both modern and fossil members of Homo. The evolving hominid masticatory apparatus--traceable to a Late Miocene, chimpanzee-like morphology--shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo. Here, we show that the gene encoding the predominant myosin heavy chain (MYH) expressed in these muscles was inactivated by a frameshifting mutation after the lineages leading to humans and chimpanzees diverged. Loss of this protein isoform is associated with marked size reductions in individual muscle fibres and entire masticatory muscles. Using the coding sequence for the myosin rod domains as a molecular clock, we estimate that this mutation appeared approximately 2.4 million years ago, predating the appearance of modern human body size and emigration of Homo from Africa. This represents the first proteomic distinction between humans and chimpanzees that can be correlated with a traceable anatomic imprint in the fossil record.

    View details for DOI 10.1038/nature02358

    View details for Web of Science ID 000220404300040

    View details for PubMedID 15042088

  • Two commonly used neoadjuvant chemoradiotherapy regimens for locally advanced stage III non-small cell lung carcinoma: Long-term results and associations with pathologic response JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Machtay, M., Lee, J. H., Stevenson, J. P., Shrager, J. B., Algazy, K. M., Treat, J., Kaiser, L. R. 2004; 127 (1): 108-113

    Abstract

    We performed this study to determine the outcomes (pathologic response, survival, local-regional control, and toxicity) in patients treated with neoadjuvant chemoradiotherapy and planned operation for stage IIIA non-small cell lung carcinoma.Patients treated from 1993 to 2000 with neoadjuvant chemoradiotherapy and a predetermined plan for subsequent surgical resection for stage III non-small cell lung carcinoma were analyzed. All patients underwent pretreatment evaluation at the university's Multidisciplinary Lung Cancer Center. Most patients (87%) had complete mediastinoscopy staging, and all were believed to be poor candidates for up-front operation because of bulky extent of disease. The radiotherapy program used conventional, 2-dimensionally planned treatment to 45 to 54 Gy in 1.8- to 2-Gy fraction size. Concurrent chemotherapy consisted of etoposide/cisplatin or carboplatin/paclitaxel. Study end points included resectability, pathologic response, local-regional control, survival, and toxicity. An exploratory comparison between pathologic response and long-term survival was performed. An exploratory comparison between older chemotherapy (etoposide/cisplatin) and third-generation chemotherapy (carboplatin/paclitaxel) was also performed.Of 53 patients, 45 (85%) were deemed surgical candidates after induction therapy. Twenty-two (42% of the initial cohort) patients had a major pathologic response to stage 0, I, or II disease. The 5-year actuarial survival was 31%. Major pathologic response was associated with improved survival (48% vs 24%; P =.027). The overall rate of early death potentially related to therapy in this series was 9%; this mostly occurred in patients who underwent right pneumonectomy. There was no difference in efficacy or mortality between etoposide/cisplatin and radiotherapy versus carboplatin/paclitaxel and radiotherapy, although the latter regimen was associated with less grade 3 or higher acute toxicity necessitating interruption or hospitalization during neoadjuvant treatment (P =.02). In-field local control was achieved in 83% of all patients (90% of the patients who underwent resection). Brain metastases as the first site of treatment failure occurred in 23% of all patients.Neoadjuvant concurrent chemoradiation delivers high resectability, major pathologic response rate, and excellent local-regional control, with encouraging long-term survival considering the patient population studied. Major pathologic response correlates with long-term survival. Neoadjuvant carboplatin/paclitaxel and radiotherapy is an appropriate framework on which to add new therapies.

    View details for DOI 10.1016/j.jtcvs.2003.07.027

    View details for Web of Science ID 000188709800018

    View details for PubMedID 14752420

  • Comparison of stages I-II thymoma treated by complete resection with or without adjuvant radiation ANNALS OF THORACIC SURGERY Singhal, S., Shrager, J. B., Rosenthal, D. I., LiVolsi, V. A., Kaiser, L. R. 2003; 76 (5): 1635-1641

    Abstract

    Adjuvant radiation after resection of Masaoka stage II thymoma is widely advocated, but the evidence supporting it is controversial. Studies addressing this issue generally report few patients and lump all patients beyond stage I together in the analysis.We retrospectively compared outcomes of stage I and II thymomas treated by resection alone with thymomas treated by resection plus radiation. Histology was re-reviewed to confirm pathologic staging and resection margin status.Between February 1992 and 2002, we performed 167 resections for thymoma. Of these, 70 patients were believed to have tumors in stage IIb or less intraoperatively, and all of these patients underwent complete resection. We reviewed the histopathology of 62 of 70 patients. Thirty thymomas demonstrated less than complete transcapsular microscopic invasion (stage I) and 40 thymomas demonstrated microscopic transcapsular invasion or macroscopic invasion into surrounding fatty tissue (stage II). Forty-seven patients underwent surgery without postoperative mediastinal radiotherapy. Dosages in the 23 radiated patients (3 stage I and 20 stage II) consisted of 45 to 55 Gy. Median follow-up was 70.3 months. Stage II patients who were radiated (n = 20) and those who were not radiated (n = 20) consisted of identical proportions in stages IIa and IIb. Two patients recurred (1 unradiated stage I patient and 1 radiated stage IIb patient). Overall 5-year survival rate was 91%. All who died were free of recurrence at time of death. Log-rank test showed no difference in Kaplan Meier survival curves (p = 0.32) between the radiated and unradiated groups.These data support the contention that margin-negative surgical resection alone is sufficient treatment for both stages I and II thymoma.

    View details for DOI 10.1016/S0003-4975(03)00819-1

    View details for Web of Science ID 000186358600056

    View details for PubMedID 14602300

  • Human diaphragm remodeling associated with chronic obstructive pulmonary disease - Clinical implications AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Levine, S., Nguyen, T., Kaiser, L. R., Rubinstein, N. A., Maislin, G., Gregory, C., Rome, L. C., Dudley, G. A., Sieck, G. C., Shrager, J. B. 2003; 168 (6): 706-713

    Abstract

    Diaphragm remodeling associated with chronic obstructive pulmonary disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsies on 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPD on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type II fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.

    View details for DOI 10.1164/rccm.200209-1070OC

    View details for Web of Science ID 000185324600016

    View details for PubMedID 12857719

  • Tracheal trauma. Chest surgery clinics of North America Shrager, J. B. 2003; 13 (2): 291-304

    Abstract

    The etiology, presentation, and management of blunt and penetrating injuries of the trachea has been reviewed. The approach to and outcome following management of more unusual situations such as iatrogenic injuries has also been briefly reviewed. Early recognition of these problems and careful attention to the details of acute management can convert a life-threatening situation into one that can usually be successfully managed by the techniques of tracheal surgery developed and popularized by Dr. Grillo.

    View details for PubMedID 12755314

  • Omentum is highly effective in the management of complex cardiothoracic surgical problems JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shrager, J. B., Wain, J. C., Wright, C. D., Donahue, D. M., Vlahakes, G. J., Moncure, A. C., Grillo, H. C., Mathisen, D. J. 2003; 125 (3): 526-532

    Abstract

    Vascularized, pedicled tissue flaps are often used for cardiothoracic surgical problems complicated by factors that adversely affect healing, such as previous irradiation, established infection, or steroid use. We reviewed our experience with use of the omentum in these situations to provide a yardstick against which results with other vascularized flaps (specifically muscle flaps) could be compared.A retrospective review was undertaken of 85 consecutive patients in whom omentum was used in the chest. In 47 patients (group I), use of omentum was prophylactic to aid in the healing of closures or anastomoses considered to be at high risk for failure. In 32 patients (group II), omentum was used in the treatment of problems complicated by established infection. In 6 patients (group III), omentum was used for coverage of prosthetic chest wall replacements after extensive chest wall resection.Overall, omental transposition was successful in its prophylactic or therapeutic purpose in 88% of these difficult cases (75/85). Success with omentum was achieved for 89% of patients (42/47) in group I, 91% of patients (29/32) in group II, and 67% of patients (4/6) in group III. Three patients (3.5%) had complications of omental mobilization. Four patients (4.7%) died after the operation as a result of failure of the omentum to manage the problem for which it was used.Results with omental transposition compare favorably with published series of similarly challenging cases managed with muscle transposition. Complications of omental mobilization are rare. We believe that its unique properties render the omentum an excellent choice of vascularized pedicle in the management of the most complex cardiothoracic surgical problems.

    View details for DOI 10.1067/mtc.2003.12

    View details for Web of Science ID 000181949800015

    View details for PubMedID 12658194

  • Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema RESPIRATORY RESEARCH Kim, D. K., Zhu, J. L., Kozyak, B. W., Burkman, J. M., Rubinstein, N. A., Lankford, E. B., Stedman, H. H., Nguyen, T., LEVINE, S., Shrager, J. B. 2003; 4 (1)

    Abstract

    Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema.We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro.In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 +/- 2.7 ms versus 53.9 +/- 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema.This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans.

    View details for Web of Science ID 000181146600001

    View details for PubMedID 12617755

  • Inspiratory loading does not accelerate dystrophy in mdx mouse diaphragm: implications for regenerative therapy JOURNAL OF APPLIED PHYSIOLOGY Krupnick, A. S., Zhu, J. L., Nguyen, T., Kreisel, D., Balsara, K. R., Lankford, E. B., Clark, C. C., LEVINE, S., Stedman, H. H., Shrager, J. B. 2003; 94 (2): 411-419

    Abstract

    Since the finding that the mdx mouse diaphragm, in contrast to limb muscles, undergoes progressive degeneration analogous to that seen in Duchenne muscular dystrophy, the relationship between the workload on a muscle and the pathogenesis of dystrophy has remained controversial. We increased the work performed by the mdx mouse diaphragm in vivo by tracheal banding and evaluated the progression of dystrophic changes in that muscle. Despite the establishment of dramatically increased respiratory workload and accelerated myofiber damage documented by Evans blue dye, no change in the pace of progression of dystrophy was seen in banded animals vs. unbanded, sham-operated controls. At the completion of the study, more centrally nucleated fibers were evident in the diaphragms of banded mdx mice than in sham-operated mdx controls, indicating that myofiber regeneration increases to meet the demands of the work-induced damage. These data suggest that there is untapped regenerative capacity in dystrophin-deficient muscle and validates experimental efforts aimed at augmenting regeneration within skeletal muscle as a therapeutic strategy in the treatment of dystrophinopathies.

    View details for DOI 10.1152/japplphysiol.00689.2002

    View details for Web of Science ID 000180437600001

    View details for PubMedID 12531909

  • Mediastinal talcoma masquerading as thymoma ANNALS OF THORACIC SURGERY Ahmed, Z., Shrager, J. B. 2003; 75 (2): 568-569

    Abstract

    We report a young woman with a large, calcified anterior mediastinal mass discovered 18 months following a left talc pleurodesis. The lesion was evaluated and treated as the thymoma or teratoma that it appeared to be, with excision by a transcervical approach. Pathologic examination revealed a giant talc granuloma. Awareness of such a possibility following talc pleurodesis may allow surgeons to avoid unnecessary mediastinal exploration, and its occurrence suggests that talc administration simultaneous with mechanical pleurodesis should be avoided.

    View details for Web of Science ID 000180926000057

    View details for PubMedID 12607675

  • Evaluating respiratory muscle adaptations - A new approach AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LEVINE, S., Nguyen, T., Kaiser, L. R., Shrager, J. B. 2002; 166 (11): 1418-1419

    View details for DOI 10.1164/rccm.2209001

    View details for Web of Science ID 000179590900002

    View details for PubMedID 12450930

  • Benign expectoration of a surgical clip through a pneumonectomy stump JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Ahmed, Z., Kaiser, L. R., Shrager, J. B. 2002; 124 (5): 1025-1026

    View details for DOI 10.1067/mtc.2002.124495

    View details for Web of Science ID 000179012300023

    View details for PubMedID 12407389

  • Transcervical thymectomy for myasthenia gravis achieves results comparable to thymectomy by sternotomy ANNALS OF THORACIC SURGERY Shrager, J. B., Deeb, M. E., Mick, R., Brinster, C. J., Childers, H. E., Marshall, M. B., Kucharczuk, J. C., Galetta, S. L., Bird, S. J., Kaiser, L. R. 2002; 74 (2): 320-326

    Abstract

    It remains controversial whether transcervical thymectomy offers results equivalent to thymectomy by way of a median sternotomy in the treatment of myasthenia gravis. Furthermore, preoperative prognostic factors have not been clearly defined.This study is a retrospective chart review and interview of 78 patients completing transcervical thymectomy for myasthenia gravis between 1992 and 1999.There were 24 men and 54 women. Mean age was 40 years (range, 13 to 78 years). Twelve patients were in Osserman class 1, 25 in class 2, 30 in class 3, and 11 in class 4 (mean, 2.5). There was no perioperative mortality and 6 (7.7%) morbidities. Mean length of stay was 1.5 days and mean follow-up, 54.6 months. The crude cumulative complete remission (asymptomatic off medications for 6 months) rate was 39.7% (n = 31). Only 8 patients (10.3%) failed to improve after transcervical thymectomy. Kaplan-Meier estimates of complete remission were 31% and 43% at 2 and 5 years, respectively. Eight patients with thymoma had a 5-year estimated complete remission rate of 75% in contrast to 43% in 38 patients with thymic hyperplasia and 36% in 32 patients with neither thymoma nor hyperplasia (p = 0.01). Twelve patients with ocular myasthenia had a 5-year estimated complete remission rate of 57%, whereas patients with mild-to-moderate (n = 55) or severe (n = 11) generalized symptoms had 5-year complete remission rates of 43% and 30%, respectively (p = 0.21).Overall, extended transcervical thymectomy offers results that are comparable to those published for the transsternal procedure. Patients with milder disease (including isolated ocular disease) and taking no preoperative immunosuppressive agents appear to experience higher remission rates. In contrast to previous studies, we also find that small thymomas predict better responses to thymectomy.

    View details for Web of Science ID 000177320600006

    View details for PubMedID 12173807

  • Pathological response to preoperative chemoradiation worsens with anemia in non-small cell lung cancer patients CANCER JOURNAL Robnett, T. J., Machtay, M., Hahn, S. M., Shrager, J. B., Freidberg, J. S., Kaiser, L. R. 2002; 8 (3): 263-267

    Abstract

    Positive links between hemoglobin level and therapeutic tumor response are well documented in carcinoma of the cervix and the head and neck, but little evidence of such a link exists for lung cancer. We analyzed our series of patients treated with preoperative chemoradiation for stage IIIA non-small cell lung carcinoma.Between June 1992 and February 2000, 41 consecutive patients with clinical stage IIIA (N2, documented by mediastinoscopy or another invasive procedure) non-small cell lung carcinoma received preoperative-intent chemoradiation. The median preoperative radiation dose was 48.6 Gy, and all patients received cisplatin- or paclitaxel-based chemotherapy. Response was graded on a four point scale: (1) progressive disease before surgery and/or technically inoperable; (2) stable disease with resection performed, but specimen containing > 50% viable tumor; (3) partial response with specimen containing < 50% tumor; and (4) complete response or near-complete response: RO resection with no residual carcinoma or pT1NO with only microscopic residual foci. Pretreatment hemoglobin values were correlated with pathological outcome using ANOVA and the non-parametric test for trend across ordered groups.The mean hemoglobin level for groups 1 through 4 was 11.8, 12.1, 12.5, and 13.2 respectively, and the association was statistically significant. If the analysis was limited to patients actually undergoing surgery (eliminating group 1), the association remained significant. The nonparametric test for trend across ordered groups was also significant with and without group 1.Our analysis supports the hypothesis that response to chemoradiation of non-small cell lung carcinoma improves with increasing hemoglobin levels.

    View details for Web of Science ID 000176142200009

    View details for PubMedID 12074326

  • Evolutionary implications of three novel members of the human sarcomeric myosin heavy chain gene family MOLECULAR BIOLOGY AND EVOLUTION Desjardins, P. R., Burkman, J. M., Shrager, J. B., Allmond, L. A., Stedman, H. H. 2002; 19 (4): 375-393

    Abstract

    Sarcomeric myosin heavy chain (MyHC) is the major contractile protein of striated muscle. Six tandemly linked skeletal MyHC genes on chromosome 17 and two cardiac MyHC genes on chromosome 14 have been previously described in the human genome. We report the identification of three novel human sarcomeric MyHC genes on chromosomes 3, 7, and 20, which are notable for their atypical size and intron-exon structure. Two of the encoded proteins are structurally most like the slow-beta MyHC, whereas the third one is closest to the adult fast IIb isoform. Data from pairwise comparisons of aligned coding sequences imply the existence of ancestral genomes with four sarcomeric genes before the emergence of a dedicated smooth muscle MyHC gene. To further address the evolutionary relationships of the distinct sarcomeric and nonsarcomeric rod sequences, we have identified and further annotated human genomic DNA sequences corresponding to 14 class-II MyHCs. An extensive analysis provides a timeline for intron gain and loss, gene contraction and expansion, and gene conversion among genes encoding class-II myosins. One of the novel human genes is found to have introns at positions shared only with the molluscan catchin/MyHC gene, providing evidence for the structure of a pre-Cambrian ancestral gene.

    View details for Web of Science ID 000174967000002

    View details for PubMedID 11919279

  • Suction vs water seal after pulmonary resection - A randomized prospective study CHEST Marshall, M. B., Deeb, M. E., Bleier, J. I., Kucharczuk, J. C., Friedberg, J. S., Kaiser, L. R., Shrager, J. B. 2002; 121 (3): 831-835

    Abstract

    To evaluate whether suction or water seal is superior in the management of chest tubes after pulmonary resection.A prospective, randomized, controlled trial. After an initial, brief period of suction, patients were randomized to water seal or - 20 cm H(2)O suction.University hospital.Sixty-eight patients who underwent wedge resection, segmentectomy, or lobectomy were included in the study. Those patients who underwent reoperative surgery or lung volume reduction surgery were excluded.There were 34 patients in each group. The two groups were evenly matched for age, sex, operation performed, severity of lung disease, and nutritional status. Fifteen patients in each group (44%) had an air leak at the completion of surgery. The duration of the air leak was shorter in the water seal group than in the suction group (mean +/- SEM, 1.50 +/- 0.32 days vs 3.27 +/- 0.80 days, respectively; p = 0.05). The mean times to removal of chest tubes were 3.33 +/- 0.35 days in the water seal group and 5.47 +/- 0.98 days in the suction group (p = 0.06). The length of stapled parenchyma was measured for each patient and averaged 24.9 cm for the water seal group and 18.5 cm for the suction group (p = 0.18). When corrected for the length of staple lines, the duration of air leaks and days with chest tube were dramatically lower in the water seal group (p = 0.02 and p = 0.02, respectively).Placing chest tubes on water seal after a brief period of suction after pulmonary resection shortens the duration of the air leak and likely decreases the time that the chest tubes remain in place. Adoption of this practice may result in lower morbidity and lower hospital costs.

    View details for Web of Science ID 000174446000029

    View details for PubMedID 11888968

  • Current presentation and optimal surgical management of sternoclavicular joint infections ANNALS OF THORACIC SURGERY Song, H. K., Guy, T. S., Kaiser, L. R., Shrager, J. B. 2002; 73 (2): 427-431

    Abstract

    Infection of the stemoclavicular joint is unusual, and treatment of this entity has not been standardized. We sought to characterize the current presentation and optimal management of this disease.We retrospectively reviewed the records of the last 7 patients undergoing operation for suppurative infections of the stemoclavicular joint at this institution. Patients were interviewed regarding upper extremity function after formal joint resection.Predisposing factors were common and included diabetes mellitus (n = 2), clavicular fracture (n = 1), human immunodeficiency virus infection (n = 1), immunosuppression (n = 1), and pustular skin disease (n = 1). All patients presented with local symptoms including clavicular mass and tenderness. Diagnosis and evaluation were facilitated by cross-sectional imaging. Organisms isolated included Staphylococcus aureus, group G streptococcus, and Proteus and Propionibacterium species. Antibiotic therapy and simple drainage and debridement were generally ineffective, leading to recurrence of infection in 5 of 6 patients treated initially in this manner. Six patients were treated with resection of the stemoclavicular joint and involved portions of first or second ribs with soft tissue coverage by advancement flap from the ipsilateral pectoralis major muscle. Response to this therapy was excellent, with cure in all patients, no wound complications, and excellent upper extremity function at long-term follow-up.Aggressive surgical management including resection of the sternoclavicular joint and involved ribs with pectoralis flap closure would appear to be the preferred treatment for all but the most minor infections of the sternoclavicular joint. This approach has minimal impact on upper extremity function.

    View details for Web of Science ID 000173624500014

    View details for PubMedID 11845854

  • Sarcomeres are added in series to emphysematous rat diaphragm after lung volume reduction surgery CHEST Shrager, J. B., Kim, D. K., Hashmi, Y. J., Stedman, H. H., Zhu, J. L., Kaiser, L. R., LEVINE, S. 2002; 121 (1): 210-215

    Abstract

    The diaphragm adapts to its shortened state in experimental emphysema primarily by losing sarcomeres in series, thus reducing its optimal operating length. One would expect improved diaphragmatic function after lung volume reduction surgery (LVRS) only if the muscle can readapt to its elevated, lengthened postoperative position by either adding back sarcomeres or lengthening sarcomeres. We used a model of elastase-induced emphysema in rats to test the hypothesis that sarcomere addition occurs following LVRS.A cohort of emphysematous rats was created by the intratracheal instillation of elastase. Five months after the instillation, one group of rats underwent measurement of in situ costal diaphragm length via laparotomy, the determination of optimal muscle fiber operating length (Lo) on stimulated diaphragm strips in vitro, and the measurement of sarcomere length by electron microscopy on strips fixed at Lo. Another group of rats underwent LVRS or sham sternotomy 5 months after the instillation, and 5 months following the operation these animals underwent the same series of diaphragmatic studies.Lo was significantly greater in rats that underwent LVRS than those that underwent sternotomy (mean [+/- SE] Lo after LVRS, 2.50 +/- 0.08 cm; mean Lo after sternotomy, 2.27 +/- 0.06 cm; p = 0.013). There was no significant difference in sarcomere lengths between the two groups (2.95 +/- 0.04 vs 3.04 +/- 0.04 microm, respectively; p = 0.10). Using Lo as the length basis, the mean sarcomere number was calculated to be 8,712 +/- 192 in animals that had undergone LVRS and 7,144 +/- 249 in animals that had undergone sternotomy (p < 0.001).Sarcomere length is not significantly altered but sarcomeres are added in series following LVRS in this experimental model of emphysema/LVRS. It is likely that this sarcomere addition is a prerequisite to the improvement in inspiratory muscle function that has been observed following LVRS in humans.

    View details for Web of Science ID 000173431400035

    View details for PubMedID 11796453

  • Osteogenic sarcoma presenting with lung metastasis ONCOLOGIST Staddon, A. P., Lackman, R., Robinson, K., Shrager, J. B., Warhol, M. 2002; 7 (2): 144-153

    Abstract

    A patient with osteogenic sarcoma presenting with lung metastases is discussed with attention to appropriate diagnosis, staging, and treatment. Multimodality treatment options using chemotherapy, orthopedic surgery and thoracic surgery are presented. Physical medicine and rehabilitation evaluation and treatment are included. Current research options are discussed.

    View details for Web of Science ID 000175213300010

    View details for PubMedID 11961198

  • Risk of death from intercurrent disease is not excessively increased by modern postoperative radiotherapy for high-risk resected non-small-cell lung carcinoma JOURNAL OF CLINICAL ONCOLOGY Machtay, M., Lee, J. H., Shrager, J. B., Kaiser, L. R., Glatstein, E. 2001; 19 (19): 3912-3917

    Abstract

    Some studies report a high risk of death from intercurrent disease (DID) after postoperative radiotherapy (XRT) for non-small-cell lung cancer (NSCLC). This study determines the risk of DID after modern-technique postoperative XRT.A total of 202 patients were treated with surgery and postoperative XRT for NSCLC. Most patients (97%) had pathologic stage II or III disease. Many patients (41%) had positive/close/uncertain resection margins. The median XRT dose was 55 Gy with fraction size of 1.8 to 2 Gy. The risk of DID was calculated actuarially and included patients who died of unknown/uncertain causes. Median follow-up was 24 months for all patients and 62 months for survivors.A total of 25 patients (12.5%) died from intercurrent disease, 16 from confirmed noncancer causes and nine from unknown causes. The 4-year actuarial rate of DID was 13.5%. This is minimally increased compared with the expected rate for a matched population (approximately 10% at 4 years). On multivariate analysis, age and radiotherapy dose were borderline significant factors associated with a higher risk of DID (P =.06). The crude risk of DID for patients receiving less than 54 Gy was 2% (4-year actuarial risk 0%) versus 17% for XRT dose > or = 54 Gy. The 4-year actuarial overall survival was 34%; local control was 84%; and freedom from distant metastases was 37%.Modern postoperative XRT for NSCLC does not excessively increase the risk of intercurrent deaths. Further study of postoperative XRT, particularly when using more sophisticated treatment planning and reasonable total doses, for carefully selected high-risk resected NSCLC is warranted.

    View details for Web of Science ID 000171246200003

    View details for PubMedID 11579111

  • Successful-experience with simultaneous lung volume reduction and cardiac procedures JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shrager, J. B., Kozyak, B. W., Roberts, J. R., Bavaria, J. E., Friedberg, J. S., Kaiser, L. R., Rosengard, B. R. 2001; 122 (1): 196-197

    View details for Web of Science ID 000169837100035

    View details for PubMedID 11436063

  • Expanded indications for transcervical thymectomy in the management of anterior mediastinal masses ANNALS OF THORACIC SURGERY Deeb, M. E., Brinster, C. J., Kucharzuk, J., Shrager, J. B., Kaiser, L. R. 2001; 72 (1): 208-211

    Abstract

    Transcervical thymectomy (TCT) is an accepted though controversial approach for thymectomy in myasthenia gravis (MG). The suggestion of thymoma on computed tomography (CT) has been considered a contraindication to TCT. We sought to determine whether the indications for TCT could be safely expanded to include selected patients with thymomas as well as other types of anterior mediastinal masses.Between January 1992 and September 1999, we performed 121 TCTs: 98 in patients with MG and 23 in patients without MG. The patients' records were retrospectively reviewed.Among the 98 MG patients, 28 had CT scans suspicious for thymoma. Of these, 14 had a thymoma pathologically. These were classified as stage I (5), stage II (8), and stage III (1). Five patients required extension of the incision for completion of the procedure. There have been no thymoma recurrences to date with a mean follow-up of 48 months (range 3 to 96 months). In the 23 patients without MG, 12 had new anterior mediastinal masses, 4 had a history of treated lymphoma, 1 had a history of treated germ cell tumor, and 6 had suspected mediastinal parathyroid adenoma. Diagnostic tissue was obtained in all patients undergoing the procedure for diagnosis, and in 4 of 6 patients, a parathyroid adenoma was successfully resected.Transcervical exploration and thymectomy offers a less invasive approach to the diagnosis and/or definitive treatment of selected anterior mediastinal masses. We suggest that it is appropriate to expand its use to several clinical scenarios beyond the typical indication of thymectomy in MG patients without thymoma.

    View details for Web of Science ID 000169906500049

    View details for PubMedID 11465181

  • Bronchial anastomotic stricture caused by ossification of an intercostal muscle flap ANNALS OF THORACIC SURGERY Deeb, M. E., Sterman, D. H., Shrager, J. B., Kaiser, L. R. 2001; 71 (5): 1700-1702

    Abstract

    We report a case of heterotopic ossification of a pedicled intercostal muscle flap that had been wrapped circumferentially around a bronchial sleeve anastomosis. This ossification caused severe bronchial stenosis and recurrent pneumonias. Stent insertion failed, and the patient ultimately required completion pneumonectomy. We recommended that caution be used when wrapping intercostal muscle around any important lumen.

    View details for Web of Science ID 000168734300065

    View details for PubMedID 11383836

  • Lobectomy with tangential pulmonary artery resection without regard to pulmonary function ANNALS OF THORACIC SURGERY Shrager, J. B., Lambright, E. S., McGrath, C. M., Wahl, P. M., Deeb, M. E., Friedberg, J. S., Kaiser, L. R. 2000; 70 (1): 234-239

    Abstract

    Non-small cell carcinoma of the lung invading the pulmonary artery (PA) has traditionally been treated by pneumonectomy. Although PA resection and reconstruction (PAR) has begun to gain acceptance, previous series of PAR by the simplest technique of tangential excision and primary repair have been unfavorable. We have maintained a policy of performing PAR preferentially whenever anatomically feasible, and usually this has been possible by tangential excision and primary repair. This study sought to determine if this approach is sound.Retrospective clinical and pathologic review.Thirty-three PARs were performed from 1992 to 1999. The patients, followed 6 to 65 months (mean 25), were aged 36 to 80 years (mean 61), and their tumors were pathologic stage IB (n = 7), IIB (n = 13), IIIA (n = 9), and IIIB (n = 4). The mean preoperative forced expiratory volume in 1 second was 70% predicted. The procedures included 14 bronchial sleeve lobectomies with PAR and 19 simple lobectomies with PAR. The PARs were performed without heparinization and included 19 tangential excisions with primary closure, 11 larger tangential excisions with pericardial patch closure, and 3 sleeve resections. There were no operative deaths and 2 (6.1%) early major complications, all unrelated to the PAR. Thirteen patients (39%) had early minor complications. Four-year Kaplan-Meier survival was 48.3% for stages I/II and 45% for stage III. Ipsilateral, central, intrathoracic recurrence occurred in 3 patients (9.1%).These data are not dramatically different from those reported for standard resections. Although the numbers are small, the results suggest that lobectomy with PAR by tangential excision is an acceptable alternative to pneumonectomy whenever anatomically possible.

    View details for Web of Science ID 000088318100052

    View details for PubMedID 10921714

  • Human skeletal myosin heavy chain genes are tightly linked in the order embryonic-IIa-IId/x-IIb-perinatal-extraocular JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY Shrager, J. B., Desjardins, P. R., Burkman, J. M., Konig, S. K., Stewart, D. R., Su, L., Shah, M. C., Bricklin, E., Tewari, M., Hoffman, R., Rickels, M. R., Jullian, E. H., Rubinstein, N. A., Stedman, H. H. 2000; 21 (4): 345-355

    Abstract

    Myosin heavy chain (MyHC) is the major contractile protein of muscle. We report the first complete cosmid cloning and definitive physical map of the tandemly linked human skeletal MyHC genes at 17p13.1. The map provides new information on the order, size, and relative spacing of the genes. and it resolves uncertainties about the two fastest twitch isoforms. The physical order of the genes is demonstrated to contrast with the temporal order of their developmental expression. Furthermore, nucleotide sequence comparisons allow an approximation of the relative timing of five ancestral duplications that created distinct genes for the six isoforms. A firm foundation is provided for molecular analysis in patients with suspected primary skeletal myosinopathies and for detailed modelling of the hypervariable surface loops which dictate myosin's kinetic properties.

    View details for Web of Science ID 000089137300005

    View details for PubMedID 11032345

  • Lung volume reduction surgery. Current problems in surgery Shrager, J. B., Kaiser, L. R., Edelman, J. D. 2000; 37 (4): 253-317

    View details for PubMedID 10778395

  • Lymphangioleiomyomatosis: The surgeon's role in diagnosis JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Deeb, M., Shrager, J. B., Edelman, J. D., Kaiser, L. 2000; 119 (3): 622-623

    View details for Web of Science ID 000085766600043

    View details for PubMedID 10694627

  • Thoracoscopic lung biopsy - Five commonly asked questions about video-assisted thoracic surgery POSTGRADUATE MEDICINE Shrager, J. B., Kaiser, L. R. 1999; 106 (4): 139-?

    Abstract

    VATS has proved to be an extremely useful diagnostic tool. Perhaps its most frequent application has been in lung biopsy to diagnose indeterminate solitary pulmonary nodules and interstitial infiltrates. In many institutions, VATS procedures have largely replaced previous methods of attempting to establish the nature of a solitary pulmonary nodule. In ambulatory patients with indeterminate infiltrates, VATS techniques have prompted earlier referral to establish a tissue diagnosis, with apparently decreased morbidity. VATS has clearly found a place in the modern practice of thoracic surgery and is likely to play an ever-increasing role in the management of diseases of the chest.

    View details for Web of Science ID 000083166900017

    View details for PubMedID 10533514

  • Bronchopulmonary carcinoid tumors associated with Cushing's syndrome: A more aggressive variant of typical carcinoid JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shrager, J. B., Wright, C. D., Wain, J. C., Torchiana, D. F., Grillo, H. C., Mathisen, D. J. 1997; 114 (3): 367-375

    Abstract

    Our objectives were to delineate the clinicopathologic characteristics of adrenocorticotropin-secreting bronchopulmonary carcinoid tumors causing Cushing's syndrome and to derive from these findings a rational approach to diagnosis and surgical management of this unusual condition.We conducted a retrospective, chart-review analysis of seven consecutive patients treated at the Massachusetts General Hospital over a 16-year period.The patients uniformly had symptoms of marked hypercortisolism, and the underlying lung lesions remained clinically occult for a mean of 24 months. Standard endocrine testing was misleading in 83% of patients, reinforcing the need for an alternative diagnostic strategy based on petrosal sinus catheterization and computed tomography of the chest. Although 72% of the tumors were typical carcinoids by standard criteria, 57% demonstrated microscopic evidence of local invasiveness, and 43% were associated with mediastinal lymph node metastases. Eighty-six percent of patients have been cured by pulmonary resection a mean of 59 months after the operation, but 50% of these required a second operation for resection of involved lymph nodes after an initial relapse.These data suggest that adrenocorticotropin-secreting bronchopulmonary carcinoid tumors represent a distinct, more aggressive subtype of the usual, typical carcinoid. The high rate of lymphatic and local spread demands a surgical approach consisting of anatomic resection and routine mediastinal lymph node dissection.

    View details for Web of Science ID A1997XW44900008

    View details for PubMedID 9305189

  • Treatment of refractory, nonmalignant hydrothorax with a pleurovenous shunt ANNALS OF THORACIC SURGERY Park, S. Z., Shrager, J. B., Allen, M. S., Nagorney, D. M. 1997; 63 (6): 1777-1779

    Abstract

    We present a case of long-term successful application of pleurovenous shunting for the management of pleural effusion. Intractable symptomatic hydrothorax developed as a result of transdiaphragmatic migration of hepatic ascites. After failure of traditional treatment by mechanical pleurodesis, a pleurovenous shunt was inserted. After 1 year of follow-up, the effusion is well controlled, and the shunt remains patent.

    View details for Web of Science ID A1997XH23000055

    View details for PubMedID 9205188

  • VIDEO-ASSISTED THORACIC-SURGERY - THE CURRENT STATE-OF-THE-ART AMERICAN JOURNAL OF ROENTGENOLOGY Kaiser, L. R., Shrager, J. B. 1995; 165 (5): 1111-1117

    Abstract

    Surgical thoracoscopy (or pleuroscopy) has historically been underused in the diagnosis and therapy of diseases of the chest. The rapid developments in laparoscopy in recent years caused thoracic surgeons to reconsider the use of endoscopic techniques in surgery of the chest. Advances in video camera technology and the use of digital processing technology so expanded the potential of thoracoscopy that an entirely new set of procedures, called video-assisted thoracic surgery, has emerged. This article reviews situations in which video-assisted procedures have proven useful, the techniques by which these procedures are performed, and the rationale behind using the video-assisted in lieu of the open approach. Video-assisted surgery often allows one to accomplish the same goal as the comparable open procedure but with less morbidity and a shorter hospital stay. With continued development of instrumentation, increasingly complex procedures continue to be accomplished. It is important for radiologists to be aware of these new developments in minimally invasive surgery, as the techniques have major implications for the practice of chest medicine and surgery as a whole. The evolution of the management of the solitary pulmonary nodule is but one example of the way video-assisted thoracic surgery has called into question the traditional approach to diseases of the chest.

    View details for Web of Science ID A1995TA73300017

    View details for PubMedID 7572485

  • VILLOUS ADENOMA OF THE MAIN PANCREATIC DUCT - A CLUE TO THE PATHOGENESIS OF PANCREATIC MALIGNANCY SURGICAL ONCOLOGY-OXFORD Shrager, J. B., GREELISH, J., VANARSDALE, C., Furth, E., Daly, J. M. 1994; 3 (4): 203-210

    Abstract

    We describe the case of a 78 year old woman with a severely dysplastic villous adenoma of the duct of Wirsung presenting with abdominal pain, emesis, weight loss, and hyperamylasemia. Abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography suggested an intraductal lesion in the head of the pancreas with a dilated distal duct. The patient underwent uncomplicated pancreaticoduodenectomy and has done well. A review of the literature on benign and malignant neoplasms of the main pancreatic duct allows formulation of the typical clinical syndrome, appropriate diagnostic work-up, treatment, and prognosis of patients with these rare lesions. The pancreatic ductal epithelium can present the full spectrum of lesions along the pathogenetic route to malignancy. This is evidence for the presence of an adenoma-to-carcinoma sequence in the pancreas analogous to that which exists in the colon.

    View details for Web of Science ID A1994PM70800002

    View details for PubMedID 7834111

  • THE VINEBERG PROCEDURE - THE IMMEDIATE FORERUNNER OF CORONARY-ARTERY BYPASS-GRAFTING ANNALS OF THORACIC SURGERY Shrager, J. B. 1994; 57 (5): 1354-1364

    Abstract

    Promulgated by the Canadian surgeon Arthur Vineberg, internal mammary artery implantation received fairly widespread clinical application during the 1960s, only to be abandoned upon the introduction of coronary artery bypass grafting toward the end of the decade. By 1978, Hurst and Logue's The Heart (4th ed. New York: McGraw-Hill, page 1291) mentioned the procedure only to relate that "indirect myocardial revascularization using the internal thoracic artery is now seldom used." Between the introduction of the operation in 1945 and the mid-1960s, a remarkably hard-fought debate raged over the value of internal mammary artery implantation. Despite the fact that coronary arteriography ultimately demonstrated the viability of Vineberg's concept, for a variety of reasons the operation could not compete with coronary artery bypass grafting, and therefore rapidly fell into disuse. The central role the Vineberg procedure has played in the evolution of coronary revascularization surgery highlights the importance of reviewing the history of its development, application, and eventual abandonment. The Vineberg procedure was, after all, the first intervention documented to increase myocardial perfusion. Recent reports of long-term graft patency and clear patient benefit with internal mammary artery implants reinforce the belief that Vineberg should be given more credit for his work than he has generally received, and that internal mammary artery implantation should not be relegated to the status of a historical curiosity.

    View details for Web of Science ID A1994NL63100069

    View details for PubMedID 7910011

  • ADAPTATIONS IN MYOSIN HEAVY-CHAIN EXPRESSION AND CONTRACTILE FUNCTION IN DYSTROPHIC MOUSE DIAPHRAGM AMERICAN JOURNAL OF PHYSIOLOGY Petrof, B. J., Stedman, H. H., Shrager, J. B., Eby, J., Sweeney, H. L., Kelly, A. M. 1993; 265 (3): C834-C841

    Abstract

    The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subsarcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne muscular dystrophy. The present study examined alterations in diaphragm contractile properties and myosin heavy chain (MHC) expression in young (3-4 mo) and old (22-24 mo) control and mdx mice. In young mdx mice, maximum isometric tension (Po) was reduced to 50% of control values. An increase in fibers coexpressing types I (slow) and IIa MHC as well as regenerating fibers expressing embryonic MHC occurred, whereas IIx/b fibers were decreased. In the old mdx group, Po underwent a further reduction to 25% of control, and there was a slowing of twitch kinetics along with markedly increased diaphragm endurance. These changes were associated with an approximate sevenfold increase in type I MHC fibers and virtual elimination of the IIx/b fiber population; there was no detectable embryonic MHC expression. We conclude that the mdx diaphragm responds to progressive muscle degeneration with transition to a slower phenotype associated with reduced power output and augmented muscle endurance. In the setting of progressive muscle fiber destruction, these changes may help preserve contractile function and promote greater survival of remaining muscle fibers by decreasing cellular energy requirements.

    View details for Web of Science ID A1993MA18400030

    View details for PubMedID 8214039

  • DYSTROPHIN PROTECTS THE SARCOLEMMA FROM STRESSES DEVELOPED DURING MUSCLE-CONTRACTION PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Petrof, B. J., Shrager, J. B., Stedman, H. H., Kelly, A. M., Sweeney, H. L. 1993; 90 (8): 3710-3714

    Abstract

    The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subject of speculation. In the present study, we demonstrate that dystrophin-deficient muscle fibers of the mdx mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. The level of sarcolemmal damage is directly correlated with the magnitude of mechanical stress placed upon the membrane during contraction rather than the number of activations of the muscle. These findings strongly support the proposition that the primary function of dystrophin is to provide mechanical reinforcement to the sarcolemma and thereby protect it from the membrane stresses developed during muscle contraction. Furthermore, the methodology used in this study should prove useful in assessing the efficacy of dystrophin gene therapy in the mdx mouse.

    View details for Web of Science ID A1993KX81600123

    View details for PubMedID 8475120

  • A PCR-BASED ASSAY FOR THE WILD-TYPE DYSTROPHIN GENE TRANSFERRED INTO THE MDX MOUSE MUSCLE & NERVE Shrager, J. B., Naji, A., Kelly, A. M., Stedman, H. H. 1992; 15 (10): 1133-1137

    Abstract

    Myoblast transfer has emerged as a promising treatment for inherited myopathies such as Duchenne muscular dystrophy (DMD). Further development of the technique's therapeutic potential requires an experimental system in which issues of graft rejection can be clearly discriminated from those related to myoblast biology. Here we report the development and initial application of a quantitative assay for myogenic cells bearing a wild-type dystrophin gene following transfer into the mdx mouse. The technique relies upon the ability of a mutagenizing polymerase chain reaction (PCR) primer to create a new restriction site in the amplification production of the wild-type, but not the mdx dystrophin gene. The ratio of host to donor cells can be determined from muscle biopsies as small as 1 mg, regardless of donor H-2 background. This simple technique should allow a number of basic questions related to myoblast and direct gene transfer to be addressed using the mdx mouse model.

    View details for Web of Science ID A1992JN86500011

    View details for PubMedID 1357549

  • 3 WOMEN AT JOHNS-HOPKINS - PRIVATE PERSPECTIVES ON MEDICAL COEDUCATION IN THE 1890S ANNALS OF INTERNAL MEDICINE Shrager, J. B. 1991; 115 (7): 564-569

    View details for Web of Science ID A1991GG28300010

    View details for PubMedID 1883127

  • THE MDX MOUSE DIAPHRAGM REPRODUCES THE DEGENERATIVE CHANGES OF DUCHENNE MUSCULAR-DYSTROPHY NATURE Stedman, H. H., Sweeney, H. L., Shrager, J. B., Maguire, H. C., Panettieri, R. A., Petrof, B., Narusawa, M., Leferovich, J. M., Sladky, J. T., Kelly, A. M. 1991; 352 (6335): 536-539

    Abstract

    Although murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of DMD limb muscle, although adult mice show no overt respiratory impairment. Progressive functional changes include reductions in strength (to 13.5% of control by two years of age), elasticity, twitch speed and fibre length. The collagen density rises to at least seven times that of control diaphragm and ten times that of mdx hind-limb muscle. By 1.5 years of age, similar but less severe histological changes emerge in the accessory muscles of respiration. On the basis of these findings, we propose that dystrophin deficiency alters the threshold for work-induced injury. Our data provide a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model.

    View details for Web of Science ID A1991GA22600065

    View details for PubMedID 1865908

Conference Proceedings


  • Mediastinoscopy: Still the Gold Standard Shrager, J. B. ELSEVIER SCIENCE INC. 2010: S2084-S2089

    Abstract

    Endobronchial ultrasound (EBUS-TBNA) is emerging as an alternative to mediastinoscopy for mediastinal lymph node evaluation in non-small cell lung cancer. It remains controversial whether EBUS-TBNA is as accurate as mediastinoscopy. Sensitivity appears similar to mediastinoscopy with enlarged nodes, but lower with normal-sized nodes. The false negative rate appears higher than with mediastinoscopy, so nonmalignant EBUS results may be unreliable. Two flawed studies examining costs identify a very small cost benefit to EBUS, which we will question herein. There are scenarios in which EBUS is preferable to mediastinoscopy. However, for routine staging of the upper mediastinum in non-small cell lung cancer, the benefits of EBUS over mediastinoscopy remain unproven.

    View details for DOI 10.1016/j.athoracsur.2010.02.098

    View details for Web of Science ID 000277934200086

    View details for PubMedID 20493986

  • Lung volume reduction surgery restores the normal diaphragmatic length-tension relationship in emphysematous rats Shrager, J. B., Kim, D. K., Hashmi, Y. J., Lankford, E. B., Wahl, P., Stedman, H. H., LEVINE, S., Kaiser, L. R. MOSBY-ELSEVIER. 2001: 217-224

    Abstract

    Improved respiratory muscle function is a major effect of a lung volume reduction surgery. We studied length adaptation in rat diaphragmatic muscle in an attempt to elucidate the mechanism by which diaphragmatic function improves after this controversial operation.We developed a model of elastase-induced emphysema and bilateral volume reduction through median sternotomy in rats. Five months after emphysema induction, maximum exchangeable lung volume was determined in intubated and anesthetized control animals and animals with emphysema. Costal diaphragmatic length was measured in vivo, and the length at which maximal twitch force is generated was determined on muscle strips in vitro. Also 5 months after elastase administration, another cohort underwent volume reduction or sham sternotomy. Five months after the operation, these animals were similarly studied.Lung volume was increased in emphysematous rats versus control rats (50.9 +/- 1.7 vs 45.4 +/- 1.3 mL, P =.001). Lung volume was decreased in emphysematous animals that had undergone volume reduction versus sham sternotomy (44.7 +/- 0.60 vs 49.4 +/- 1.0 mL, P =.001). In situ diaphragm length (1.99 +/- 0.04 vs 2.24 +/- 0.07 cm, P =.001) and the length at which maximal twitch force is generated (2.25 +/- 0.06 vs 2.48 +/- 0.09 cm, P =.038) were shorter in emphysematous than control animals. After volume reduction, in situ diaphragm length (2.13 +/- 0.06 vs 1.83 +/- 0.02 cm, P <.001) and the length at which maximal twitch force is generated (2.50 +/- 0.08 vs 2.27 +/- 0.06 cm, P =.013) were longer than in animals undergoing sham sternotomy.In this experimental model of emphysema and lung volume reduction surgery, emphysema shortens the length at which maximal twitch force is generated and shifts the diaphragmatic length-tension curve to lower lengths; volume reduction returns the length at which maximal twitch force is generated toward normal and shifts the diaphragmatic length-tension curve back to longer lengths. This restoration toward normal physiology may enable the improvement in diaphragmatic function seen after lung volume reduction surgery. The mechanism by which these length adaptations occur merits further investigation.

    View details for Web of Science ID 000167014300006

    View details for PubMedID 11174726

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