Dr. Wren is a board certified general surgeon who specializes in the surgical treatment of gastrointestinal cancer: including stomach, pancreas, intestinal, and colon and rectal cancers. She completed fellowship training in advanced hepatobiliary surgery and performs open, laparoscopic, and robotic approaches to these cancers.

Dr. Wren is also very involved in humanitarian surgery and global surgery. She works and manages educational partnerships in Sub Saharan Africa. She is faculty fellow of the Stanford Center for Innovation and Global Health.

Clinical Focus

  • Cancer > GI Oncology
  • Surgical Oncology
  • Colorectal Surgery
  • Surgical Procedures, Minimally Invasive
  • Robotics
  • General Surgery
  • global surgery

Academic Appointments

Administrative Appointments

  • Vice Chair Department of Surgery: Professional Development and Diversity, Department of Surgery, Stanford University (2016 - Present)
  • Honorary Professor, Barts and the London School of Medicine, Queen Mary University of London (2014 - Present)
  • Director of Clinical Surgery, Palo Alto Veterans Health Care System (2013 - Present)
  • Director Global Surgery, Center for Innovation and Global Health: Stanford University (2011 - Present)
  • Faculty Fellow, Center for Innovation and Global Health (2011 - Present)
  • Associate Dean, Academic Affairs, Stanford University School of Medicine (2008 - 2014)
  • Govenor, American College of Surgeons (2008 - 2014)
  • President, American College of Surgeons, Northern CA Chapter (2008 - 2009)
  • Chair, Committee on Student Promotion, Professionalism, and Performance, Stanford University School of Medicine (2007 - 2011)
  • Chair, Faculty Senate, Stanford University Medical School Faculty Senate (2006 - 2008)
  • Residency Site Director, Stanford University, PAVAHCS (2003 - Present)
  • Surgical Clerkship Director, Stanford University School of Medicine (2000 - 2008)
  • Chief of General Surgery, Palo Alto Veterans Health Care System (1997 - Present)
  • Cancer Liaison Program Physician, American College of Surgeons Commission on Cancer Program (1997 - 2011)

Honors & Awards

  • International Humanitarian Volunteerism Award, American College of Surgeons (October 2017)
  • Olga Jonnason Distinguished Member Award, Association of Women Surgeons (October 17, 2016)
  • Editorial Board, World Journal of Surgery (2018)
  • Editorial Board, JAMA Surgery (2010)
  • Alumni of the Year, Loyola Stritch School of Medicine (2009)
  • Cancer Liaison Physician Outstanding Performance Award, Commission on Cancer (2008)
  • John Austin Collins Memorial Award for Outstanding Dedication to Resident Teaching, Stanford University Department of Surgery (2007)
  • Kaiser Foundation Award for Excellence in Clinical Teaching, Stanford University School of Medicine (2006)
  • Outstanding Teacher Award, Association of Surgical Education (2005)
  • The Arthur L. Bloomfield Award for Excellence in Teaching of Clinical Medicine, Stanford University School of Medicine (2003)
  • The Franklin G. Ebaugh Award for Outstanding Dedication to Medical Student Advising, Stanford University School of Medicine (2002)
  • The Henry J. Kaiser Award for Excellence in Clinical Teaching, Stanford University School of Medicine (2002)
  • Editorial Board, Surgical Endoscopy (2000)
  • Editorial Board, Journal of Laparoendoscopic and Advanced Surgical Techniques (2000)
  • The Arthur L. Bloomfield Award for Excellence in Teaching of Clinical Medicine, The Franklin G. Ebaugh Award for Outstanding Dedication to Medical Student Advising (1999)

Boards, Advisory Committees, Professional Organizations

  • Member, Society of American Gastrointestinal Endoscopic Surgeons (1996 - Present)
  • Member, Society of Surgery of Alimentary Tract (1997 - Present)
  • Member, American College of Surgeons (1997 - Present)
  • Member, San Francisco Surgical Society (1998 - Present)
  • Member, Northern California Chapter, American College of Surgeons (1998 - Present)
  • Member, Pacific Coast Surgical Association (1999 - Present)
  • Member, Society of Surgical Oncology (2000 - Present)
  • Member, American Hepato-Pancreato-Biliary Association (2002 - Present)
  • Member, Western Surgical Society (2003 - Present)
  • Member, Society of University Surgeons (2005 - Present)
  • Member, Halsted Surgical Society (2006 - Present)
  • Member, American Surgical Association (2009 - Present)
  • Member, International Surgical Society (2010 - Present)
  • Fellow, College of Surgeons of East, Central, and Southern Africa (2013 - Present)

Professional Education

  • Medical Education:Loyola University Stritch School of Medicine (1986) IL
  • Board Certification: General Surgery, American Board of Surgery (1995)
  • Fellowship:LAC and USC Medical Center (1995) CA
  • Residency:University of Pittsburgh Medical Center (1994) PA
  • Residency:Yale - New Haven Hospital (1989) CT
  • Fellowship:University of Pittsburgh School of Medicine (1992) PA
  • Internship:Yale - New Haven Hospital (1987) CT
  • MD, Loyola University, MD (1986)
  • B.A., Carleton College, Biology (1981)

Community and International Work

  • Global Surgery Research, Khartoum, Sudan

    Ongoing Project


    Opportunities for Student Involvement


  • Zimbabwe


    Surgical research



    Ongoing Project


    Opportunities for Student Involvement


  • Northwest Cameroon, Cameroon


    Surgical Clinical Research



    Ongoing Project


    Opportunities for Student Involvement


Current Research and Scholarly Interests

Our research interests are primarily in global surgery, quality improvement and surgical oncology, especially gastrointestinal cancers.We have ongoing studies in medical management trials for post operative ileus, robotics, pneumonia prevention, telehealth, and care delivery in low income settings.

2017-18 Courses

Stanford Advisees

All Publications

  • Health Care Providers in War and Armed Conflict: Operational and Educational Challenges in International Humanitarian Law and the Geneva Conventions, Part II. Educational and Training Initiatives. Disaster medicine and public health preparedness Burkle, F. M., Kushner, A. L., Giannou, C., Paterson, M. A., Wren, S. M., Burnham, G. 2018: 1–14


    ABSTRACTNo discipline has been impacted more by war and armed conflict than health care has. Health systems and health care providers are often the first victims, suffering increasingly heinous acts that cripple the essential health delivery and public health infrastructure necessary for the protection of civilian and military victims of the state at war. This commentary argues that current instructional opportunities to prepare health care providers fall short in both content and preparation, especially in those operational skill sets necessary to manage multiple challenges, threats, and violations under international humanitarian law and to perform triage management in a resource-poor medical setting. Utilizing a historical framework, the commentary addresses the transformation of the education and training of humanitarian health professionals from the Cold War to today followed by recommendations for the future. (Disaster Med Public Health Preparedness. 2018;page 1 of 14).

    View details for DOI 10.1017/dmp.2018.42

    View details for PubMedID 29733000

  • A Framework for a Battlefield Trauma System for Civilians. Annals of surgery Garber, K., Stewart, B. T., Burkle, F. M., Kushner, A. L., Wren, S. M. 2018

    View details for DOI 10.1097/SLA.0000000000002691

    View details for PubMedID 29373367

  • Electricity and generator availability in LMIC hospitals: improving access to safe surgery. The Journal of surgical research Chawla, S., Kurani, S., Wren, S. M., Stewart, B., Burnham, G., Kushner, A., McIntyre, T. 2018; 223: 136–41


    Access to reliable energy has been identified as a global priority and codified within United Nations Sustainable Goal 7 and the Electrify Africa Act of 2015. Reliable hospital access to electricity is necessary to provide safe surgical care. The current state of electrical availability in hospitals in low- and middle-income countries (LMICs) throughout the world is not well known. This study aimed to review the surgical capacity literature and document the availability of electricity and generators.Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search for surgical capacity assessments in LMICs in MEDLINE, PubMed, and World Health Organization Global Health Library was performed. Data regarding electricity and generator availability were extracted. Estimated percentages for individual countries were calculated.Of 76 articles identified, 21 reported electricity availability, totaling 528 hospitals. Continuous electricity availability at hospitals providing surgical care was 312/528 (59.1%). Generator availability was 309/427 (72.4%). Estimated continuous electricity availability ranged from 0% (Sierra Leone and Malawi) to 100% (Iran); estimated generator availability was 14% (Somalia) to 97.6% (Iran).Less than two-thirds of hospitals providing surgical care in 21 LMICs have a continuous electricity source or have an available generator. Efforts are needed to improve electricity infrastructure at hospitals to assure safe surgical care. Future research should look at the effect of energy availability on surgical care and patient outcomes and novel methods of powering surgical equipment.

    View details for DOI 10.1016/j.jss.2017.10.016

    View details for PubMedID 29433865

  • What are the optimum components in a care bundle aimed at reducing post-operative pulmonary complications in high-risk patients? Perioperative medicine (London, England) Griffiths, S. V., Conway, D. H., Sander, M., Jammer, I., Grocott, M. P., Creagh-Brown, B. C. 2018; 7: 7


    Post-operative pulmonary complications (POPC) are common, predictable and associated with increased morbidity and mortality, independent of pre-operative risk. Interventions to reduce the incidence of POPC have been studied individually, but the use of a care bundle has not been widely investigated. The purpose of our work was to use Delphi consensus methodology and an independently chosen expert panel to formulate a care bundle for patients identified as being at high of POPC, as preparation towards an evaluation of its effectiveness at reducing POPC.We performed a survey of members of the ESICM POIC section to inform a Delphi consensus and to share their opinions on a care bundle to reduce POPC, the POPC-CB. We formed a team of 36 experts to participate in and complete an email-based Delphi consensus over three rounds, leading to the formulation of the POPC-CB.The survey had 362 respondents and informed the design of the Delphi consensus. The Delphi consensus resulted in a proposed POPC-CB that incorporates components before surgery-supervised exercise programmes and inspiratory muscle training, during surgery, low tidal volume ventilation with individualised PEEP (positive end-expiratory pressure), use of routine monitoring to avoid hyperoxia and efforts made to limit neuromuscular blockade, and post-operatively, deep breathing exercises and elevation of the head of the bed.A care bundle has been suggested for evaluation in surgical patients at high risk of POPC. Evaluation of feasibility of both implementation and effectiveness is now indicated.

    View details for DOI 10.1186/s13741-018-0084-9

    View details for PubMedID 29692886

    View details for PubMedCentralID PMC5904979

  • Health Care Providers in War and Armed Conflict: Operational and Educational Challenges in International Humanitarian Law and the Geneva Conventions, Part I. Historical Perspective. Disaster medicine and public health preparedness Burkle, F. M., Kushner, A. L., Giannou, C., Paterson, M. A., Wren, S. M., Burnham, G. 2018: 1–7


    Since 1945, the reason for humanitarian crises and the way in which the world responds to them has dramatically changed every 10 to 15 years or less. Planning, response, and recovery for these tragic events have often been ad hoc, inconsistent, and insufficient, largely because of the complexity of global humanitarian demands and their corresponding response system capabilities. This historical perspective chronicles the transformation of war and armed conflicts from the Cold War to today, emphasizing the impact these events have had on humanitarian professionals and their struggle to adapt to increasing humanitarian, operational, and political challenges. An unprecedented independent United Nations-World Health Organization decision in the Battle for Mosul in Iraq to deploy to combat zones emergency medical teams unprepared in the skills of decades-tested war and armed conflict preparation and response afforded to health care providers and dictated by International Humanitarian Law and Geneva Convention protections has abruptly challenged future decision-making and deployments. (Disaster Med Public Health Preparedness. 2018;page 1 of 7).

    View details for DOI 10.1017/dmp.2018.41

    View details for PubMedID 29706140

  • Sex disparities among persons receiving operative care during armed conflicts. Surgery Forrester, J. D., Forrester, J. A., Basimouneye, J., Tahir, M., Trelles, M., Kushner, A. L., Wren, S. M. 2017


    Armed conflict increasingly involves civilian populations, and health care needs may be immense. We hypothesized that sex disparities may exist among persons receiving operative care in conflict zones and sought to describe predictors of disparity.We performed a retrospective analysis of operative interventions performed between 2008 and 2014 at Médecins Sans Frontières Operation Center Brussels conflict projects. A Médecins Sans Frontières Operation Center Brussels conflict project was defined as a program established in response to human conflict, war, or social unrest. Intervention- and country-level variables were evaluated. For multivariate analysis, multilevel mixed-effects logistic regression was used with random-effect modeling to account for clustering and population differences in conflict zones.Between 2008 and 2014, 49,715 interventions were performed in conflict zones by Médecins Sans Frontières Operation Center Brussels. Median patient age was 24 years (range: 1-105 years), and 34,436 (69%) were men. Patient-level variables associated with decreased interventions on women included: American Society of Anesthesiologists score (P = .003), degree of urgency (P = .02), mechanism (P < .0001), and a country's predominant religion (P = .006). Men were 1.7 times more likely to have an operative intervention in a predominantly Muslim country (P = .006).Conflict is an unfortunate consequence of humanity in a world with limited resources. For most operative interventions performed in conflict zones, men were more commonly represented. Predominant religion was the greatest predictor of increased disparity between sexes, irrespective of the number of patients presenting as a result of traumatic injury. It is critical to understand what factors may underlie this disparity to ensure equitable and appropriate care for all patients in an already tragic situation.

    View details for DOI 10.1016/j.surg.2017.03.001

    View details for PubMedID 28400124

  • Applying Trauma Transfusion Practices to Nontrauma Care: A Cautionary Tale. JAMA surgery Rinderknecht, T. N., Wren, S. M. 2017

    View details for DOI 10.1001/jamasurg.2017.0091

    View details for PubMedID 28273302

  • Reasons for faculty departures from an academic medical center: a survey and comparison across faculty lines BMC MEDICAL EDUCATION Girod, S. C., Fassiotto, M., Menorca, R., Etzkowitz, H., Wren, S. M. 2017; 17


    Faculty departure can present significant intellectual costs to an institution. The authors sought to identify the reasons for clinical and non-clinical faculty departures at one academic medical center (AMC).In May and June 2010, the authors surveyed 137 faculty members who left a west coast School of Medicine (SOM) between 1999 and 2009. In May and June 2015, the same survey was sent to 40 faculty members who left the SOM between 2010-2014, for a total sample size of 177 former faculty members. The survey probed work history and experience, reasons for departure, and satisfaction at the SOM versus their current workplace. Statistical analyses included Pearson's chi-square test of independence and independent sample t-tests to understand quantitative differences between clinical and non-clinical respondents, as well as coding of qualitative open-ended responses.Eighty-eight faculty members responded (50%), including three who had since returned to the SOM. Overall, professional and advancement opportunities, salary concerns, and personal/family reasons were the three most cited factors for leaving. The average length of time at this SOM was shorter for faculty in clinical roles, who expressed lower workplace satisfaction and were more likely to perceive incongruence and inaccuracy in institutional expectations for their success than those in non-clinical roles. Clinical faculty respondents noted difficulty in balancing competing demands and navigating institutional expectations for advancement as reasons for leaving.AMCs may not be meeting faculty needs, especially those in clinical roles who balance multiple missions as clinicians, researchers, and educators. Institutions should address the challenges these faculty face in order to best recruit, retain, and advance faculty.

    View details for DOI 10.1186/s12909-016-0830-y

    View details for Web of Science ID 000392450500001

    View details for PubMedID 28073345

    View details for PubMedCentralID PMC5223325

  • Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years. The British journal of surgery Powell, J. T., Sweeting, M. J., Ulug, P., Blankensteijn, J. D., Lederle, F. A., Becquemin, J. P., Greenhalgh, R. M. 2017; 104 (3): 166–78


    The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation.An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention.The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization.The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.

    View details for DOI 10.1002/bjs.10430

    View details for PubMedID 28160528

  • Gender and Specialty Influences on Personal and Professional Life Among Trainees. Annals of surgery Rogers, A. C., Wren, S. M., McNamara, D. A. 2017


    This study aimed to determine the impact of surgical training on lifestyle and parenthood, and to assess for gender-based workplace issues.The effects of a surgical career on lifestyle are difficult to quantify and may vary between male and female doctors. A gender gap is present in the highest tiers of the profession, and reasons why women do not attain senior positions are complex but likely relate to factors beyond merit alone.An anonymous Web-based survey was distributed to Irish surgical and nonsurgical trainees. They were asked questions regarding family planning, pregnancy outcomes, parenthood, and gender issues in the workplace, with results analyzed by sex and specialty.Four hundred sixty trainees responded with a response rate of 53.0%; almost two thirds were female. Female trainee surgeons were less likely to have children than their male counterparts (22.5% vs 40.0%, P = 0.0215). Pregnant surgical trainees were more likely to have adverse pregnancy events than the partners of their male contemporaries (65.0% vs 11.5%, P = 0.0002), or than their female nonsurgical colleagues (P = 0.0329). Women were more likely to feel that they had missed out on a job opportunity (P < 0.001) and that their fellowship choice was influenced by their gender (P < 0.001).The current study highlights some areas of difficulty encountered by female surgical trainees. Surmounting the barriers to progression for female surgeons, by addressing the perceived negative impacts of surgery on lifestyle, will likely encourage trainee retention of both genders.

    View details for DOI 10.1097/SLA.0000000000002580

    View details for PubMedID 29099401

  • Trends in Country-Specific Surgical Randomized Clinical Trial Publications. JAMA surgery Forrester, J. A., Forrester, J. D., Wren, S. M. 2017

    View details for DOI 10.1001/jamasurg.2017.4867

    View details for PubMedID 29282466

  • Using Epidemiology to Determine Surgical Needs in Low-Resource Settings. JAMA surgery Forrester, J. D., Wren, S. M. 2017: e174027

    View details for DOI 10.1001/jamasurg.2017.4027

    View details for PubMedID 29071330

  • Sex Differences in Civilian Injury in Baghdad From 2003 to 2014: Results of a Randomized Household Cluster Survey. Annals of surgery Shaak, K., Lafta, R., Stewart, B. T., Fowler, T. R., Al-Shatari, S. A., Burnham, G., Cherewick, M., Wren, S. M., Groen, R. S., Kushner, A. L. 2017


    To examine sex differences in injury mechanisms, injury-related death, injury-related disability, and associated financial consequences in Baghdad since the 2003 invasion of Iraq to inform prevention initiatives, health policy, and relief planning.Reliable estimates of injury burden among civilians during conflict are lacking, particularly among vulnerable subpopulations, such as women.A 2-stage, cluster randomized, community-based household survey was conducted in May 2014 to determine the civilian burden of injury in Baghdad since 2003. Households were surveyed regarding injury mechanisms, healthcare required, disability, deaths, connection to conflict, and resultant financial hardship.We surveyed 900 households (5148 individuals), reporting 553 injuries, 162 (29%) of which were injuries among women. The mean age of injury was higher among women compared with men (34 ± 21.3 vs 27 ± 16.5 years; P < 0.001). More women than men were injured while in the home [104 (64%) vs 82 (21%); P < 0.001]. Fewer women than men died from injuries [11 (6.8%) vs 77 (20%); P < 0.001]; however, women were more likely than men to live with reduced function [101 (63%) vs 192 (49%); P = 0.005]. Of intentional injuries, women had higher rates of injury by shell fragments (41% vs 26%); more men were injured by gunshots [76 (41%) vs 6 (17.6%); P = .011).Women experienced fewer injuries than men in postinvasion Baghdad, but were more likely to suffer disability after injury. Efforts to improve conditions for injured women should focus on mitigating financial and provisional hardships, providing counseling services, and ensuring access to rehabilitation services.

    View details for DOI 10.1097/SLA.0000000000002140

    View details for PubMedID 28151803

  • Consensus recommendations for essential vascular care in low- and middle-income countries JOURNAL OF VASCULAR SURGERY Stewart, B. T., Gyedu, A., Giannou, C., Mishra, B., Rich, N., Wren, S. M., Mock, C., Kushner, A. L. 2016; 64 (6): 1770-?


    Many low- and middle-income countries (LMICs) are ill equipped to care for the large and growing burden of vascular conditions. We aimed to develop essential vascular care recommendations that would be feasible for implementation at nearly every setting worldwide, regardless of national income.The normative Delphi method was used to achieve consensus on essential vascular care resources among 27 experts in multiple areas of vascular care and public health as well as with experience in LMIC health care. Five anonymous, iterative rounds of survey with controlled feedback and a statistical response were used to reach consensus on essential vascular care resources.The matrices provide recommendations for 92 vascular care resources at each of the four levels of care in most LMICs, comprising primary health centers and first-level, referral, and tertiary hospitals. The recommendations include essential and desirable resources and encompass the following categories: screening, counseling, and evaluation; diagnostics; medical care; surgical care; equipment and supplies; and medications.The resources recommended have the potential to improve the ability of LMIC health care systems to respond to the large and growing burden of vascular conditions. Many of these resources can be provided with thoughtful planning and organization, without significant increases in cost. However, the resources must be incorporated into a framework that includes surveillance of vascular conditions, monitoring and evaluation of vascular capacity and care, a well functioning prehospital and interhospital transport system, and vascular training for existing and future health care providers.

    View details for DOI 10.1016/j.jvs.2016.05.046

    View details for Web of Science ID 000390044000034

    View details for PubMedID 27432199

  • Beyond Infrastructure: Understanding Why Patients Decline Surgery in the Developing World: An Observational Study in Cameroon. Annals of surgery Lerman, B. J., Alsan, M., Chia, N. J., Brown, J. A., Wren, S. M. 2016: -?


    The aim of this study was to quantify and describe a population of patients in rural Cameroon who present with a surgically treatable illness but ultimately decline surgery, and to understand the patient decision-making process and identify key socioeconomic factors that result in barriers to care.An estimated 5 billion people lack access to safe, affordable surgical care and anesthesia when needed, and this unmet need resides disproportionally in low-income countries (LICs). An understanding of the socioeconomic factors underlying decision-making is key to future efforts to expand surgical care delivery in this population. We assessed patient decision-making in a LIC with a cash-based health care economy.Standardized interviews were conducted of a random sample of adult patients with treatable surgical conditions over a 7-week period in a tertiary referral hospital in rural Cameroon. Main outcome measures included participant's decision to accept or decline surgery, source of funding, and the relative importance of various factors in the decision-making process.Thirty-four of 175 participants (19.4%) declined surgery recommended by their physician. Twenty-six of 34 participants declining surgery (76.4%) cited procedure cost, which on average equaled 6.4 months' income, as their primary decision factor. Multivariate analysis revealed female gender [odds ratio (OR) 3.35, 95% confidence interval (95% CI) 2.14-5.25], monthly earnings (OR 0.83, 95% CI, 0.77-0.89), supporting children in school (OR 1.22, 95% CI 1.13-1.31), and inability to borrow funds from family or the community (OR 6.49, 95% CI 4.10-10.28) as factors associated with declining surgery.Nearly one-fifth of patients presenting to a surgical clinic with a treatable condition did not ultimately receive needed surgery. Both financial and sociocultural factors contribute to the decision to decline care.

    View details for PubMedID 27849672

  • Enhancing Local Resources in Low- and Middle-Income Countries Through Education. JAMA surgery Yang, G. P., Wren, S. M. 2016

    View details for DOI 10.1001/jamasurg.2016.3365

    View details for PubMedID 27706484

  • Geographic Variation in Surgical Outcomes and Cost Between the United States and Japan AMERICAN JOURNAL OF MANAGED CARE Hurley, M. P., Schoemaker, L., Morton, J. M., Wren, S. M., Vogt, W. B., Watanabe, S., Yoshikawa, A., Bhattacharya, J. 2016; 22 (9): 600-?


    Unwarranted geographic variation in spending has received intense scrutiny in the United States. However, few studies have compared variation in spending and surgical outcomes between the United States healthcare system and those of other nations. In this study, we compare the geographic variation in postsurgical outcomes and cost between the United States and Japan.This retrospective cohort study uses Medicare Part A data from the United States (2010-2011) and similar inpatient data from Japan (2012). Patients 65 years or older undergoing 1 of 5 surgeries (coronary artery bypass graft, abdominal aortic aneurysm repair, colectomy, pancreatectomy, or gastrectomy) were selected in the United States and Japan.Reliability- and case-mix-adjusted coefficient of variation (COV) values were calculated using hierarchical modeling and empirical Bayes techniques for the following 5 outcomes: postoperative mortality, the development of a complication, death after complication (failure to rescue), length of stay, and the cost of the hospitalization. Sensitivity analyses were also performed by calculating patient demographic-and case-mix-adjusted COV values for each outcome using weighted age- and sex-standardized values.The variability of the postsurgical outcomes was uniformly lower in the United States compared with Japan. Cost variation was consistently higher in the United States for all surgeries.Although the US healthcare system may be more inefficient regarding costs, the presence of higher geographic variation in postoperative care in Japan, relative to the United States, suggests that the observed geographic variation in the United States-both for health expenditures and outcomes-is not a unique manifestation of its structural shortcomings.

    View details for Web of Science ID 000384740300009

    View details for PubMedID 27662222

  • Urgent and Elective Robotic Single-Site Cholecystectomy: Analysis and Learning Curve of 150 Consecutive Cases JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES Kubat, E., Hansen, N., Nguyen, H., Wren, S. M., Eisenberg, D. 2016; 26 (3): 185-191
  • Self-reported Determinants of Access to Surgical Care in 3 Developing Countries JAMA SURGERY Forrester, J. D., Forrester, J. A., Kamara, T. B., Groen, R. S., Shrestha, S., Gupta, S., Kyamanywa, P., Petroze, R. T., Kushner, A. L., Wren, S. M. 2016; 151 (3): 257-263
  • Urgent and Elective Robotic Single-Site Cholecystectomy: Analysis and Learning Curve of 150 Consecutive Cases. Journal of laparoendoscopic & advanced surgical techniques. Part A Kubat, E., Hansen, N., Nguyen, H., Wren, S. M., Eisenberg, D. 2016; 26 (3): 185-191


    The use of robotic single-site cholecystectomy has increased exponentially. There are few reports describing the safety, efficacy, and operative learning curve of robotic single-site cholecystectomy either in the community setting or with nonelective surgery.We performed a retrospective review of a prospective database of our initial experience with robotic single-site cholecystectomy. Demographics and perioperative outcomes were evaluated for both urgent and elective cholecystectomy. Cumulative sum analysis was performed to determine the surgeon's learning curve.One hundred fifty patients underwent robotic single-site cholecystectomy. Seventy-four (49.3%) patients underwent urgent robotic single-site cholecystectomy, and 76 (50.7%) underwent elective robotic single-site cholecystectomy. Mean total operative time for robotic single-site cholecystectomy was 83.3 ± 2.7 minutes. Mean operative time for the urgent cohort was significantly longer than for the elective cohort (95.0 ± 4.4 versus 71.9 ± 2.6 minutes; P < .001). There was one conversion in the urgent cohort and none in the elective cohort. There was one bile duct injury (0.7%) in the urgent cohort. Perioperative complications occurred in 8.7% of patients, and most consisted of superficial surgical-site infections. There were no incisional hernias detected. The surgeon's learning curve, inclusive of urgent and elective cases, was 48 operations.Robotic single-site cholecystectomy can be performed safely and effectively in both elective and urgent cholecystectomy with a reasonable learning curve and acceptable perioperative outcomes.

    View details for DOI 10.1089/lap.2015.0528

    View details for PubMedID 26756715

  • Self-reported Determinants of Access to Surgical Care in 3 Developing Countries. JAMA surgery Forrester, J. D., Forrester, J. A., Kamara, T. B., Groen, R. S., Shrestha, S., Gupta, S., Kyamanywa, P., Petroze, R. T., Kushner, A. L., Wren, S. M. 2016; 151 (3): 257-263


    Surgical care is recognized as a growing component of global public health.To assess self-reported barriers to access of surgical care in Sierra Leone, Rwanda, and Nepal using the validated Surgeons OverSeas Assessment of Surgical Need tool.Data for this cross-sectional, cluster-based population survey were collected from households in Rwanda (October 2011), Sierra Leone (January 2012), and Nepal (May and June 2014) using the Surgeons OverSeas Assessment of Surgical Need tool.Basic demographic information, cost and mode of transportation to health care facilities, and barriers to access to surgical care of persons dying within the past year were analyzed.A total of 4822 households were surveyed in Nepal, Rwanda, and Sierra Leone. Primary health care facilities were commonly reached rapidly by foot (>70%), transportation to secondary facilities differed by country, and public transportation was ubiquitously required for access to a tertiary care facility (46%-82% of respondents). Reasons for not seeking surgical care when needed included no money for health care (Sierra Leone: n = 103; 55%), a person dying before health care could be arranged (all countries: 32%-43%), no health care facility available (Nepal: n = 11; 42%), and a lack of trust in health care (Rwanda: n = 6; 26%).Self-reported determinants of access to surgical care vary widely among Sierra Leone, Rwanda, and Nepal, although commonalities exist. Understanding the epidemiology of barriers to surgical care is essential to effectively provide surgical service as a public health commodity in developing countries.

    View details for DOI 10.1001/jamasurg.2015.3431

    View details for PubMedID 26536154

  • Process improvement in surgery CURRENT PROBLEMS IN SURGERY Minami, C. A., Sheils, C. R., Bilimoria, K. Y., Johnson, J. K., Berger, E. R., Berian, J. R., Englesbe, M. J., Guillamondegui, O. D., Hines, L. H., Cofer, J. B., Flum, D. R., Thiriby, R. C., Kazaure, H. S., Wren, S. M., O'Leary, K. J., Thurk, J. L., Kennedy, G. D., Tevis, S. E., Yang, A. D. 2016; 53 (2): 62-96

    View details for DOI 10.1067/j.cpsurg.2015.11.001

    View details for Web of Science ID 000369351000002

    View details for PubMedID 26806271

  • Infant, maternal, and geographic factors influencing gastroschisis related mortality in Zimbabwe. Surgery Apfeld, J. C., Wren, S. M., Macheka, N., Mbuwayesango, B. A., Bruzoni, M., Sylvester, K. G., Kastenberg, Z. J. 2015; 158 (6): 1475-1480


    Survival for infants with gastroschisis in developed countries has improved dramatically in recent decades with reported mortality rates of 4-7%. Conversely, mortality rates for gastroschisis in sub-Saharan Africa remain as great as 60% in contemporary series. This study describes the burden of gastroschisis at the major pediatric hospital in Zimbabwe with the goal of identifying modifiable factors influencing gastroschisis-related infant mortality.We performed a retrospective cohort study of all cases of gastroschisis admitted to Harare Children's Hospital in 2013. Univariate and multivariate analyses were performed to describe infant, maternal, and geographic factors influencing survival.A total of 5,585 neonatal unit admissions were identified including 95 (1.7%) infants born with gastroschisis. Gastroschisis-related mortality was 84% (n = 80). Of infants with gastroschisis, 96% (n = 91) were born outside Harare Hospital, 82% (n = 78) were born outside Harare Province, and 23% (n = 25) were home births. The unadjusted odds of survival for these neonates with gastroschisis were decreased for low birth weight infants (<2,500 grams; odds ratio [OR], 0.15; 95% CI, 0.05-0.51), preterm births (<37 weeks gestational age; OR, 0.06; 95% CI, 0.01-0.50), and for those born to teenage mothers (<20 years of age; OR, 0.05; 95% CI, 0.01-0.46). There was also a trend toward decreased odds of survival for home births (OR, 0.16; 95% CI, 0.02-1.34) and for those born outside Harare Province (OR, 0.35; 95% CI, 0.10-1.22).Gastroschisis-related infant mortality in Zimbabwe is associated with well-known risk factors, including low birth weight, prematurity, and teenage mothers. However, modifiable factors identified in this study signify potential opportunities for developing innovative approaches to perinatal care in such a resource-constrained environment.

    View details for DOI 10.1016/j.surg.2015.04.037

    View details for PubMedID 26071924

  • Infant, maternal, and geographic factors influencing gastroschisis related mortality in Zimbabwe SURGERY Apfeld, J. C., Wren, S. M., Macheka, N., Mbuwayesango, B. A., Bruzoni, M., Sylvester, K. G., Kastenberg, Z. J. 2015; 158 (6): 1476-1481
  • Missing the obvious: psychosocial obstacles in Veterans with hepatocellular carcinoma HPB Hwa, K. J., Dua, M. M., Wren, S. M., Visser, B. C. 2015; 17 (12): 1124-1129


    Socioeconomic disparities in patients with hepatocellular carcinoma (HCC) influence medical treatment. In addition to socioeconomic barriers, the Veteran population suffers from significant psychosocial obstacles. This study identifies the social challenges that Veterans face while undergoing treatment for HCC.One hundred Veterans at the Palo Alto VA treated for HCC from 2009 to 2014 (50 consecutive patients who underwent a surgical procedure; 50 treated with intra-arterial therapy) were retrospectively reviewed.Substance abuse history was identified in 96%, and half were unemployed. Most patients survived on a limited income [median $1340, interquartile range (IQR) 900-2125]; 36% on ≤ $1000/month, 37% between $1001-2000/month and 27% with >$2000/month. A history of homelessness was found in 30%, more common in those of the lowest income (57% of ≤$1K/month group, 23% of $1-2K/month group and 9% of >$2K/month group, P < 0.01). Psychiatric illness was present in 64/100 patients; among these the majority received ongoing psychiatric treatment. Transportation was provided to 23% of patients who would otherwise have been unable to attend medical appointments.Psychiatric disease and substance abuse are highly prevalent among Veterans with HCC. Most patients survive on a very meager income. These profound socioeconomic and psychosocial problems must be recognized when providing care for HCC to this population to provide adequate treatment and surveillance.

    View details for DOI 10.1111/hpb.12508

    View details for Web of Science ID 000368291100010

  • Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes The ACOSOG Z6051 Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Fleshman, J., Branda, M., Sargent, D. J., Boller, A. M., George, V., Abbas, M., Peters, W. R., Maun, D., Chang, G., Herline, A., Fichera, A., Mutch, M., Wexner, S., Whiteford, M., Marks, J., Birnbaum, E., Margolin, D., Larson, D., Marcello, P., Posner, M., Read, T., Monson, J., Wren, S. M., Pisters, P. W., Nelson, H. 2015; 314 (13): 1346-1355


    Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease.To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen.A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection.Standard laparoscopic and open approaches were performed by the credentialed surgeons.The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimation.Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7% of laparoscopic resection cases (95% CI, 76.8%-86.6%) and 86.9% of open resection cases (95% CI, 82.5%-91.4%) and did not support noninferiority (difference, -5.3%; 1-sided 95% CI, -10.8% to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3% of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95% CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95% CI, -0.6 to 1.1), readmission within 30 days (3.3% vs 4.1%; difference, -0.7%; 95% CI, -4.2% to 2.7%), and severe complications (22.5% vs 22.1%; difference, 0.4%; 95% CI, -4.2% to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5% of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3% open resection; P = .11). Distal margin result was negative in more than 98% of patients irrespective of type of surgery (P = .91).Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these Identifier: NCT00726622.

    View details for DOI 10.1001/jama.2015.10529

    View details for Web of Science ID 000362644700012

    View details for PubMedID 26441179

  • Factors associated with delays to surgical presentation in North-West Cameroon SURGERY Long, C., Tagang, E. T., Popat, R. A., Lawong, E. K., Brown, J. A., Wren, S. M. 2015; 158 (3): 756-763


    Few studies have examined critically the delays in definitive management for surgical diseases in Sub-Saharan Africa. This study investigates factors contributing to delays at Mbingo Baptist Hospital, a tertiary referral hospital in Cameroon.During a 6-week period, we randomly interviewed 220 patients (39.2%) admitted to the surgical or orthopedic service and/or their caregivers. All patients >age 15 years admitted with a diagnosis of cancer or urgent operative condition (defined as requiring a definitive operation within 48 hours of admission) including trauma were interviewed. Delay was defined as receiving treatment >7 days after symptoms appeared in the urgent cohort and >1 month for the cancer cohort.In the urgent cohort, 60.3% patients had delays >7 days to hospital presentation. Compared with nondelayed patients, delayed patients were more likely to have sought care >1 day after symptoms appeared (45.4% vs 6.3%, P < .0001) and to have received previous medical care (92.8% vs 73.4%, P = .0007). Of all patients who received previous care, those with delays, compared those with no delays, visited ≥2 other providers (50.5% vs 18.8%, P < .0001), received a surgical procedure at previous episode(s) of care (21.1% vs 6.4%, P = .026), and felt no improvement after this care (80.4% vs 61.0%, P = .003). In the cancer cohort, 100% experienced >1 month delay. 100% had received medical care prior to arriving at Mbingo Baptist Hospital, 81.4% sought care from at least 3 different facilities, and none believed this care addressed their health concerns.Significant delays most often were caused by time spent on previous failed attempts at care. This information can be used to inform policy discussions about optimal health care organization within the country.

    View details for DOI 10.1016/j.surg.2015.04.016

    View details for Web of Science ID 000359755000022

    View details for PubMedID 26067462

  • Global opportunities on 239 general surgery residency Web sites JOURNAL OF SURGICAL RESEARCH Wackerbarth, J. J., Campbell, T. D., Wren, S., Price, R. R., Maier, R. V., Numann, P., Kushner, A. L. 2015; 198 (1): 115-119
  • Promoting quality of care in disaster response: A survey of core surgical competencies SURGERY Wong, E. G., Razek, T., Elsharkawi, H., Wren, S. M., Kushner, A. L., Giannou, C., Khwaja, K. A., Beckett, A., Deckelbaum, D. L. 2015; 158 (1): 78-84


    Recent humanitarian crises have led to a call for professionalization of the humanitarian field, but core competencies for the delivery of surgical care have yet to be established. The objective of this study was to survey surgeons with experience in disaster response to identify surgical competencies required to be effective in these settings.An online survey elucidating demographic information, scope of practice, and previous experience in global health and disaster response was transmitted to surgeons from a variety of surgical societies and nongovernmental organizations. Participants were provided with a list of 111 operative procedures and were asked to identify those deemed essential to the toolset of a frontline surgeon in disaster response via a Likert scale. Responses from personnel with experience in disaster response were contrasted with those from nonexperienced participants.A total of 147 surgeons completed the survey. Participants held citizenship in 22 countries, were licensed in 30 countries, and practiced in >20 countries. Most respondents (56%) had previous experience in humanitarian response. The majority agreed or strongly agreed that formal training (54%), past humanitarian response (94%), and past global health experiences (80%) provided adequate preparation. The most commonly deemed important procedures included control of intraabdominal hemorrhage (99%), abdominal packing for trauma (99%), and wound debridement (99%). Procedures deemed important by experienced personnel spanned multiple specialties.This study addressed specifically surgical competencies in disaster response. We provide a list of operative procedures that should set the stage for further structured education programs.

    View details for DOI 10.1016/j.surg.2015.02.011

    View details for Web of Science ID 000356320400012

    View details for PubMedID 25843337

  • Recommendations for including surgery on the public health agenda JOURNAL OF SURGICAL RESEARCH Wong, E. G., Ameh, E. A., Wren, S. M., Mulwafu, W., Hardy, M. A., Nwomeh, B. C., Kushner, A. L., Price, R. R. 2015; 197 (1): 112-117


    Surgical care has made limited inroads on the public health and global health agendas despite increasing data showing the enormous need. The objective of this study was to survey interested members of a global surgery community to identify patterns of thought regarding barriers to political priority.All active members of the nongovernmental organization Surgeons OverSeas were surveyed and asked why surgical care is not receiving recognition and support on the public health and global health agenda. Responses were categorized using the Shiffman framework on determinants of political priority for global initiatives by two independent investigators, and the number of responses for each of the 11 factors was calculated.Seventy-five Surgeons OverSeas members replied (75 of 176; 42.6% response rate). A total of 248 individual reasons were collected. The most common responses were related to external frame, defined as public portrayals of the issue (60 of 248; 24.2%), and lack of effective interventions (48 of 248; 19.4%). Least cited reasons related to global governance structure (4 of 248; 2.4%) and policy window (4 of 248; 1.6%).This survey of a global surgery community identified a number of barriers to the recognition of surgical care on the global health agenda. Recommendations include improving the public portrayal of the problem; developing effective interventions and seeking strong and charismatic leadership.

    View details for DOI 10.1016/j.jss.2015.04.020

    View details for Web of Science ID 000355554900018

    View details for PubMedID 25940158

  • Injury prevalence and causality in developing nations: Results from a countrywide population-based survey in Nepal SURGERY Gupta, S., Wong, E. G., Nepal, S., Shrestha, S., Kushner, A. L., Nwomeh, B. C., Wren, S. M. 2015; 157 (5): 843-849


    Traumatic injury affects nearly 5.8 million people annually and causes 10% of the world's deaths. In this study we aimed to estimate injury prevalence, to describe risk-factors and mechanisms of injury, and to estimate the number of injury-related deaths in Nepal, a low-income South Asian country.A cluster randomized, cross-sectional nationwide survey using the Surgeons OverSeas Assessment of Surgical Need tool was conducted in Nepal in 2014. Questions were structured anatomically and designed around a representative spectrum of operative conditions. Two-stage cluster sampling was performed: 15 of 75 districts were chosen randomly proportional to population; within each district, after stratification for urban and rural populations, 3 clusters were randomly chosen. Injury-related results were analyzed.A total of 1,350 households and 2,695 individuals were surveyed verbally, with a response rate of 97%. A total of 379 injuries were reported in 354 individuals (13.1%, 95% confidence interval 11.9-14.5%), mean age of 32.6. The most common mechanism of injury was falls (37.5%), road traffic injuries (19.8%), and burns (14.2%). The most commonly affected anatomic site was the upper extremity (42.0%). Of the deaths reported in the previous year, 16.3% were injury-related; 10% of total deaths may have been averted with access to operative care.This study provides baseline data on the epidemiology of traumatic injuries in Nepal and is the first household-based countrywide assessment of injuries in Nepal. These data provide valuable information to help advise policymakers and government officials for allocation of resources toward trauma care.

    View details for DOI 10.1016/j.surg.2014.12.020

    View details for Web of Science ID 000368557100003

  • Injury assessment in three low-resource settings: a reference for worldwide estimates. Lancet Gupta, S., Wren, S. M., Kamara, T. B., Shrestha, S., Kyamanywa, P., Wong, E. G., Groen, R. S., Nwomeh, B. C., Kushner, A. L., Price, R. R. 2015; 385: S2-?


    Trauma has become a worldwide pandemic. Without dedicated public health interventions, fatal injuries will rise 40% and become the 4th leading cause of death by 2030, with the burden highest in low-income and middle-income countries (LMICs). The aim of this study was to estimate the prevalence of traumatic injuries and injury-related deaths in low-resource countries worldwide, using population-based data from the Surgeons OverSeas Assessment of Surgical Need (SOSAS), a validated survey tool.Using data from three resource-poor countries (Nepal, Rwanda, and Sierra Leone), a weighted average of injury prevalence and deaths due to injury was calculated and extrapolated to low-resource countries worldwide. Injuries were defined as wounds from road traffic injuries (bus, car, truck, pedestrian, and bicycle), gunshot or stab or slash wounds, falls, work or home incidents, and burns. The Nepal study included a visual physical examination that confirmed the validity of the self-reported data. Population and annual health expenditure per capita data were obtained from the World Bank. Low-resource countries were defined as those with an annual per capita health expenditure of US$100 or less.The overall prevalence of lifetime injury for these three countries was 18·03% (95% CI 18·02-18·04); 11·64% (95% CI 11·53-11·75) of deaths annually were due to injury. An estimated prevalence of lifetime injuries for the total population in 48 low-resource countries is 465·7 million people; about 2·6 million fatal injuries occur in these countries annually.The limitations of this observational study with self-reported data include possible recall and desirability bias. About 466 million people at a community level (18%) sustain at least one injury during their lifetime and 2·6 million people die annually from trauma in the world's poorest countries. Trauma care capacity should be considered a global health priority; the importance of integrating a coordinated trauma system into any health system should not be underestimated.None.

    View details for DOI 10.1016/S0140-6736(15)60797-8

    View details for PubMedID 26313066

  • Surgical care needs of low-resource populations: an estimate of the prevalence of surgically treatable conditions and avoidable deaths in 48 countries. Lancet Gupta, S., Groen, R. S., Kyamanywa, P., Ameh, E. A., Labib, M., Clarke, D. L., Donkor, P., Derbew, M., Sani, R., Kamara, T. B., Shrestha, S., Nwomeh, B. C., Wren, S. M., Price, R. R., Kushner, A. L. 2015; 385: S1-?


    Surgical care needs in low-resource countries are increasingly recognised as an important aspect of global health, yet data for the size of the problem are insufficient. The Surgeons OverSeas Assessment of Surgical Need (SOSAS) is a population-based cluster survey previously used in Nepal, Rwanda, and Sierra Leone.Using previously published SOSAS data from three resource-poor countries (Nepal, Rwanda, and Sierra Leone), a weighted average of overall prevalence of surgically treatable conditions was estimated and the number of deaths that could have been avoided by providing access to surgical care was calculated for the broader community of low-resource countries. Such conditions included, but were not limited to, injuries (road traffic incidents, falls, burns, and gunshot or stab wounds), masses (solid or soft, reducible), deformities (congenital or acquired), abdominal distention, and obstructed delivery. Population and health expenditure per capita data were obtained from the World Bank. Low-resource countries were defined as those with a per capita health expenditure of US$100 or less annually. The overall prevalence estimate from the previously published SOSAS data was extrapolated to each low-resource country. Using crude death rates for each country and the calculated proportion of avoidable deaths, a total number of deaths possibly averted in the previous year with access to appropriate surgical care was calculated.The overall prevalence of surgically treatable conditions was 11·16% (95% CI 11·15-11·17) and 25·6% (95% CI 25·4-25·7) of deaths were potentially avoidable by providing access to surgical care. Using these percentages for the 48 low-resource countries, an estimated 288·2 million people are living with a surgically treatable condition and 5·6 million deaths could be averted annually by the provision of surgical care. In the Nepal SOSAS study, the observed agreement between self-reported verbal responses and visual physical examination findings was 94·6%. Such high correlation helps to validate the SOSAS tool.Hundreds of millions of people with surgically treatable conditions live in low-resource countries, and about 25% of the mortality annually could be avoided with better access to surgical care. Strengthening surgical care must be considered when strengthening health systems and in setting future sustainable development goals.None.

    View details for DOI 10.1016/S0140-6736(15)60796-6

    View details for PubMedID 26313055

  • Telephone Follow-Up by a Midlevel Provider After Laparoscopic Inguinal Hernia Repair Instead of Face-to-Face Clinic Visit. JSLS : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons Eisenberg, D., Hwa, K., Wren, S. M. 2015; 19 (1)


    The need for more cost- and time-efficient provision of medical care has prompted an interest in remote or telehealth approaches to delivery of health care. We present a study examining the feasibility and outcomes of implementation of a telephone follow-up program for laparoscopic inguinal hernia repair.This is a retrospective review of consecutive patients who prospectively agreed to undergo telephone follow-up after laparoscopic inguinal hernia repair instead of standard face-to-face clinic visits. Patients received a telephone call from a dedicated physician assistant 2 to 3 weeks after surgery and answered a predetermined questionnaire. A face-to-face clinic visit was scheduled based on the results of the call or on patient request.Of 62 patients who underwent surgery, all agreed to telephone follow-up instead of face-to-face clinic visits. Their mean round-trip distance to the hospital was 122 miles. Fifty-five patients (88.7%) successfully completed planned telephone follow-up. Three patients (4.8%) were lost to follow-up, and 4 (6.5%) were erroneously scheduled for a clinic appointment. Of the 55 patients who were reached by telephone, 50 (90.9%) were satisfied and declined an in-person clinic visit. Five patients (9.1%) returned for a clinic appointment based on concerns raised during the telephone call. Of these, 1 was found to have an early hernia recurrence and 1 had a seroma.Telephone follow-up by a midlevel provider after laparoscopic inguinal hernia repair is feasible and effective and is well received by patients.

    View details for DOI 10.4293/JSLS.2014.00205

    View details for PubMedID 25848178

  • Burns in Sierra Leone: A population-based assessment BURNS Wong, E. G., Groen, R. S., Kamara, T. B., Stewart, K., Cassidy, L. D., Samai, M., Kushner, A. L., Wren, S. M. 2014; 40 (8): 1748-1753
  • Long-term Results of a Postoperative Pneumonia Prevention Program for the Inpatient Surgical Ward JAMA SURGERY Kazaure, H. S., Martin, M., Yoon, J. K., Wren, S. M. 2014; 149 (9): 914-918


    Pneumonia is the third most common complication in postoperative patients and is associated with significant morbidity and high cost of care. Prevention has focused primarily on mechanically ventilated patients. This study outlines the results of the longest-running postoperative pneumonia prevention program for nonmechanically ventilated patients, to our knowledge.To present long-term results (2008-2012) of a standardized postoperative ward-acquired pneumonia prevention program introduced in 2007 on the surgical ward of our hospital and compare our postintervention pneumonia rates with those captured in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). We also estimate the cost savings attributable to the pneumonia prevention program.Retrospective cohort study at a university-affiliated Veterans Affairs hospital of all noncardiac surgical patients with ward-acquired postoperative pneumonia.A previously described standardized postoperative pneumonia prevention program for patients on the surgical ward.Ward-acquired postoperative pneumonia.Between 2008 and 2012, there were 18 cases of postoperative pneumonia among 4099 at-risk patients hospitalized on the surgical ward, yielding a case rate of 0.44%. This represents a 43.6% decrease from our preintervention rate (0.78%) (P = .01). The pneumonia rates in all years were lower than the preintervention rate (0.25%, 0.50%, 0.58%, 0.68%, and 0.13% in 2008-2012, respectively). The overall pneumonia rate in ACS-NSQIP was 2.56% (14,033 cases of pneumonia among 547,571 at-risk patients), which is 582% higher than the postintervention rate at our ward. Using a national average of $46,400 in attributable health care cost of postoperative pneumonia and a benchmark of a 43.6% decrease in pneumonia rate achieved at our facility over the 5-year study period, a similar percentage of decrease in pneumonia occurrence at ACS-NSQIP hospitals would represent approximately 6118 prevented pneumonia cases and a cost savings of more than $280 million.The standardized pneumonia prevention program achieved substantial and sustained reduction in postoperative pneumonia incidence on our surgical ward; its wider adoption could improve postoperative outcomes and reduce overall health care costs.

    View details for DOI 10.1001/jamasurg.2014.1216

    View details for Web of Science ID 000342389000010

    View details for PubMedID 25054486

  • Mental stress experienced by first-year residents and expert surgeons with robotic and laparoscopic surgery interfaces. Journal of robotic surgery Klein, M. I., Mouraviev, V., Craig, C., Salamone, L., Plerhoples, T. A., Wren, S. M., Gaitonde, K. 2014; 8 (2): 149-155


    Prior research has indicated that novices experienced a beneficial stress profile in the robotic surgery (da Vinci) training environment when compared to the laparoscopic surgery training environment. The objective of this study was to assess whether this finding generalizes to expert surgeons. Towards that end, first-year residents' and attending surgeons' performances and subjective stress experiences were assessed in a surgical training task that was performed with the da Vinci and laparoscopic surgery interfaces. This study indicated that both groups exhibited superior performance and lower stress with the da Vinci surgical system than the laparoscopic system. The results provide further support for the sensitivity of the Dundee Stress State Questionnaire in identifying different stress responses experienced by trainees and experts in the minimally invasive surgery environment.

    View details for DOI 10.1007/s11701-013-0446-8

    View details for PubMedID 27637524

  • Understanding the reliability of American College of Surgeons National Surgical Quality Improvement Program as a quality comparator. JAMA surgery Rhoads, K. F., Wren, S. M. 2014; 149 (5): 474-?

    View details for DOI 10.1001/jamasurg.2013.4253

    View details for PubMedID 24623013

  • An estimate of hernia prevalence in Sierra Leone from a nationwide community survey. Hernia Patel, H. D., Groen, R. S., Kamara, T. B., SAMAI, M., Farahzad, M. M., Cassidy, L. D., Kushner, A. L., Wren, S. M. 2014; 18 (2): 297-303


    A large number of unrepaired inguinal hernias is expected in sub-Saharan Africa where late presentation often results in incarceration, strangulation, or giant scrotal hernias. However, no representative population-based data are available to quantify the prevalence of hernias. We present data on groin masses in Sierra Leone to estimate prevalence, barriers to care, and associated disability.A cluster randomized, cross-sectional household survey of 75 clusters of 25 households with 2 respondents each was designed to calculate the prevalence of and disability caused by groin hernias in Sierra Leone using a verbal head-to-toe examination. Barriers to hernia repairs were assessed by asking participants the main reason for delay in surgical care.Information was obtained from 3,645 respondents in 1,843 households, of which 1,669 (46 %) were male and included in the study. In total, 117 males or 7.01 % (95 % CI 5.64-8.38) reported a soft or reducible swelling likely representing a hernia with four men having two masses. Of the 93.2 % who indicated the need for health care, only 22.2 % underwent a procedure, citing limited funds (59.0 %) as the major barrier to care. On disability assessment, 20.2 % were not able to work secondary to the groin swelling.The results indicate groin masses represent a major burden for the male population in Sierra Leone. Improving access to surgical care for adult patients with hernias and early intervention for children will be vital to address the burden of disease and prevent complications or limitations of daily activity.

    View details for DOI 10.1007/s10029-013-1179-3

    View details for PubMedID 24241327

  • The evolving application of single-port robotic surgery in general surgery. Journal of hepato-biliary-pancreatic sciences Qadan, M., Curet, M. J., Wren, S. M. 2014; 21 (1): 26-33


    Advances in the field of minimally invasive surgery have grown since the original advent of conventional multiport laparoscopic surgery. The recent development of single incision laparoscopic surgery remains a relatively novel technique, and has had mixed reviews as to whether it has been associated with lower pain scores, shorter hospital stays, and higher satisfaction levels among patients undergoing procedures through cosmetically-appeasing single incisions. However, due to technical difficulties that arise from the clustering of laparoscopic instruments through a confined working space, such as loss of instrument triangulation, poor surgical exposure, and instrument clashing, uptake by surgeons without a specific interest and expertise in cutting-edge minimally invasive approaches has been limited. The parallel use of robotic surgery with single-port platforms, however, appears to counteract technical issues associated with single incision laparoscopic surgery through significant ergonomic improvements, including enhanced instrument triangulation, organ retraction, and camera localization within the surgical field. By combining the use of the robot with the single incision platform, the recognized challenges of single incision laparoscopic surgery are simplified, while maintaining potential advantages of the single-incision minimally invasive approach. This review provides a comprehensive report of the evolving application single-port robotic surgery in the field of general surgery today.

    View details for DOI 10.1002/jhbp.37

    View details for PubMedID 24124130

  • Innovation in Safety, and Safety in Innovation JAMA SURGERY Eisenberg, D., Wren, S. M. 2014; 149 (1): 7-9

    View details for DOI 10.1001/jamasurg.2013.5112

    View details for Web of Science ID 000330117300002

    View details for PubMedID 24352512

  • Telehealth Follow-up in Lieu of Postoperative Clinic Visit for Ambulatory Surgery Results of a Pilot Program JAMA SURGERY Hwa, K., Wren, S. M. 2013; 148 (9): 823-827


    IMPORTANCE Telehealth encounters can safely substitute for routine postoperative clinic visits in selected ambulatory surgical procedures. OBJECTIVE To examine whether an allied health professional telephone visit could safely substitute for an in-person clinic visit. DESIGN Prospective case series during a 10-month study period from October 2011 to October 2012 (excluding July and August 2012). SETTING University-affiliated veterans hospital. PATIENTS Ambulatory surgery patients who underwent elective open hernia repair or laparoscopic cholecystectomy during the 10-month study period. INTERVENTIONS Patients were called 2 weeks after surgery by a physician assistant and assessed using a scripted template. Assessment variables included overall health, pain, fever, incision appearance, activity level, and any patient concerns. If the telephone assessment was consistent with absence of infection and return to baseline activities, the patient was discharged from follow-up. Patients who preferred a clinic visit were seen accordingly. MAIN OUTCOMES AND MEASURES Percentage of patients who accepted telehealth follow-up and complications that presented in telehealth patients within 30 days of surgery. RESULTS One hundred fifteen open herniorrhaphy and 26 laparoscopic cholecystectomy patients had attempted telehealth follow-up. Seventy-eight percent (110) of all patients were successfully contacted; of those, 70.8% (63) of hernia patients and 90.5% (19) of cholecystectomy patients accepted telehealth as the sole means of follow-up. Complications in the telehealth patients were zero for cholecystectomy and 4.8% (3) for herniorrhaphy. Nearly all patients expressed great satisfaction with the telephone follow-up method. CONCLUSIONS Telehealth can be safely used in selected ambulatory patients as a substitute for the standard postoperative clinic visit with a high degree of patient satisfaction. Time and expense for travel (7-866 miles) were reduced and the freed clinic time was used to schedule new patients.

    View details for DOI 10.1001/jamasurg.2013.2672

    View details for Web of Science ID 000325212300007

    View details for PubMedID 23842982

  • Traumatic injuries in developing countries: report from a nationwide cross-sectional survey of sierra leone. JAMA surgery Stewart, K. A., Groen, R. S., Kamara, T. B., Farahzad, M. M., Samai, M., Cassidy, L. D., Kushner, A. L., Wren, S. M. 2013; 148 (5): 463-469


    OBJECTIVE To use a nationwide household survey tool to provide an estimate of injury prevalence, mechanisms of traumatic injuries, and number of injury-related deaths in a low-income country. DESIGN A randomized, cross-sectional nationwide survey using the Surgeons OverSeas Assessment of Surgical Need tool was conducted in 2012. SETTING Sierra Leone, Africa. PARTICIPANTS Three thousand seven hundred fifty randomly selected participants throughout Sierra Leone. MAIN OUTCOME MEASURES Mechanisms of injury based on age, sex, anatomic location, cause, and sociodemographic factors as well as mechanisms of injury-related deaths in the previous year were the primary outcome measures. RESULTS Data were collected and analyzed from 1843 households and 3645 respondents (98% response rate). Four hundred fifty-two respondents (12%) reported at least 1 traumatic injury in the preceding year. Falls were the most common cause of nonfatal injuries (40%). The extremities were the most common injury site regardless of age or sex. Traffic injuries were the leading cause of injury-related deaths (32% of fatal injuries). CONCLUSIONS This study provides baseline data on the mechanisms of traumatic injuries as well as the sociodemographic factors affecting injury prevalence in one of the world's poorest nations. It is anticipated that these data will provide an impetus for further studies to determine injury severity, associated disability, and barriers to accessing care in these resource-poor areas.

    View details for DOI 10.1001/jamasurg.2013.1341

    View details for PubMedID 23325317

  • The influence of intern home call on objectively measured perioperative outcomes. JAMA surgery Kastenberg, Z. J., Rhoads, K. F., Melcher, M. L., Wren, S. M. 2013; 148 (4): 347-351


    HYPOTHESIS In July 2011, surgical interns were prohibited from being on call from home by the new residency review committee guidelines on work hours. In support of the new Accreditation Council for Graduate Medical Education work-hour restrictions, we expected that a period of intern home call would correlate with increased rates of postoperative morbidity and mortality. DESIGN Prospective cohort. SETTING University-affiliated tertiary Veterans Affairs Medical Center. PATIENTS All patients identified in the Veterans Affairs National Surgical Quality Improvement Program database who underwent an operation performed by general, vascular, urologic, or cardiac surgery services between fiscal years (FYs) 1999 and 2010 were included. MAIN OUTCOME MEASURES During FYs 1999-2003, the first call for all patients went to an in-hospital intern. In the subsequent period (FYs 2004-2010), the first call went to an intern on home call. Thirty-day unadjusted morbidity and mortality rates and risk-adjusted observed to expected ratios were analyzed by univariate analysis and joinpoint regression, respectively. RESULTS Unadjusted overall morbidity rates decreased between 1999-2003 and 2004-2010 (12.14% to 10.19%, P =  .003). The risk-adjusted morbidity observed to expected ratios decreased at a uniform annual percentage change of -6.03% (P < .001). Unadjusted overall mortality rates also decreased between the 2 periods (1.76% to 1.26%; P =  .05). There was no significant change in the risk-adjusted mortality observed to expected ratios during the study. CONCLUSIONS The institution of an intern home call schedule was not associated with increased rates of postoperative morbidity or mortality.

    View details for DOI 10.1001/jamasurg.2013.1063

    View details for PubMedID 23715944

  • Long-Term Comparison of Endovascular and Open Repair of Abdominal Aortic Aneurysm NEW ENGLAND JOURNAL OF MEDICINE Lederle, F. A., Freischlag, J. A., Kyriakides, T. C., Matsumura, J. S., Padberg, F. T., Kohler, T. R., Kougias, P., Jean-Claude, J. M., Cikrit, D. F., Swanson, K. M. 2012; 367 (21): 1988-1997


    Whether elective endovascular repair of abdominal aortic aneurysm reduces long-term morbidity and mortality, as compared with traditional open repair, remains uncertain.We randomly assigned 881 patients with asymptomatic abdominal aortic aneurysms who were candidates for both procedures to either endovascular repair (444) or open repair (437) and followed them for up to 9 years (mean, 5.2). Patients were selected from 42 Veterans Affairs medical centers and were 49 years of age or older at the time of registration.More than 95% of the patients underwent the assigned repair. For the primary outcome of all-cause mortality, 146 deaths occurred in each group (hazard ratio with endovascular repair versus open repair, 0.97; 95% confidence interval [CI], 0.77 to 1.22; P=0.81). The previously reported reduction in perioperative mortality with endovascular repair was sustained at 2 years (hazard ratio, 0.63; 95% CI, 0.40 to 0.98; P=0.04) and at 3 years (hazard ratio, 0.72; 95% CI, 0.51 to 1.00; P=0.05) but not thereafter. There were 10 aneurysm-related deaths in the endovascular-repair group (2.3%) versus 16 in the open-repair group (3.7%) (P=0.22). Six aneurysm ruptures were confirmed in the endovascular-repair group versus none in the open-repair group (P=0.03). A significant interaction was observed between age and type of treatment (P=0.006); survival was increased among patients under 70 years of age in the endovascular-repair group but tended to be better among those 70 years of age or older in the open-repair group.Endovascular repair and open repair resulted in similar long-term survival. The perioperative survival advantage with endovascular repair was sustained for several years, but rupture after repair remained a concern. Endovascular repair led to increased long-term survival among younger patients but not among older patients, for whom a greater benefit from the endovascular approach had been expected. (Funded by the Department of Veterans Affairs Office of Research and Development; OVER number, NCT00094575.).

    View details for DOI 10.1056/NEJMoa1207481

    View details for Web of Science ID 000311340200006

    View details for PubMedID 23171095

  • Cost-effectiveness of open versus endovascular repair of abdominal aortic aneurysm in the OVER trial JOURNAL OF VASCULAR SURGERY Stroupe, K. T., Lederle, F. A., Matsumura, J. S., Kyriakides, T. C., Jonk, Y. C., Ge, L., Freischlag, J. A. 2012; 56 (4): 901-?


    This study was conducted to determine the costs and comparative cost-effectiveness of two methods of abdominal aortic aneurysm (AAA) repair in the Open Versus Endovascular Repair (OVER) Veterans Affairs (VA) Cooperative Study, a multicenter randomized trial of 881 patients.The primary outcomes of this analysis were mean total health care cost per life-year and per quality-adjusted life-year (QALY) from randomization to 2 years after. QALYs were calculated from EuroQol (EQ)-5D questionnaires collected at baseline and annually. Health care utilization data were obtained directly from patients and from national VA and Medicare data sources. VA costs were obtained from national VA sources using methods previously developed by the VA Health Economics Resource Center. Costs for non-VA care were determined from Medicare claims data or billing data from the patient's health care providers.After 2 years of follow-up, mean life-years were 1.78 in the endovascular repair group and 1.74 in the open repair group (difference, 0.04; 95% confidence interval [CI], -0.03 to 0.09; P = .29). Mean QALYs were 1.462 in the endovascular group and 1.461 in the open group (difference adjusting for baseline EQ-5D score, 0.006; 95% CI, -0.038 to 0.052; P = .78). Mean graft costs were higher in the endovascular group ($14,052 vs $1363; P < .001), but length of stay was shorter (5.0 vs 10.5 days; P < .001), resulting in a lower mean cost of the hospital admission for the AAA procedure in the endovascular repair group of $37,068 vs $42,970 (difference, -$5901; 95% CI, -$12,135 to -$821; P = .04). After 2 years, total health care costs remained lower in the endovascular group, but the difference was no longer significant (-$5019; 95% CI, -$16,720 to $4928; P = .35). The probability of endovascular repair being less costly and more effective was 70.9% for life-years and 51.4% for QALYs.In this multicenter randomized trial, endovascular AAA repair resulted in lower cost and better survival than open repair after the initial hospitalization for repair; but after 2 years, survival, quality of life, and costs were not significantly different between the two treatments.

    View details for DOI 10.1016/j.jvs.2012.01.086

    View details for Web of Science ID 000309512300001

    View details for PubMedID 22640466

  • The aching surgeon: a survey of physical discomfort and symptoms following open, laparoscopic, and robotic surgery. Journal of robotic surgery Plerhoples, T. A., Hernandez-Boussard, T., Wren, S. M. 2012; 6 (1): 65-72


    There is increasing interest in understanding the toll that operating takes on a surgeon's body. The effect of robotic surgery on surgeon discomfort has not been studied. We sought to document the discomfort of robotic surgery compared with open and laparoscopic surgery and to investigate the factors that affect the risk of physical symptoms. Nineteen-thousand eight-hundred and sixty-eight surgeons from all specialties trained in the use of robots were sent a 26-question online survey and 1,407 responded. One-thousand two-hundred and fifteen surgeons who practiced all three approaches were used in the analysis. Eight-hundred and seventy-one surgeons had physical discomfort or symptoms attributable to operating. Of those with symptoms, 55.4% attributed most of the symptoms to laparoscopic surgery, 36.3% to open surgery, and 8.3% to robotic surgery. A higher case load was predictive of increased symptoms for open and laparoscopic surgery, but not for robotic surgery. Robotic surgery was less likely than open or laparoscopic surgery to lead to neck, back, hip, knee, ankle, foot, and shoulder pain and less likely than laparoscopic surgery to lead to elbow and wrist pain. Robotic surgery was more likely than either open or laparoscopic surgery to lead to eye pain, and more likely than open surgery to lead to finger pain. Nearly a third (30.3%) of surgeons admit to giving consideration to their own discomfort when choosing an operative modality. Robotic surgery has promise in reducing the risk of physical discomfort for the operator. This is important as more surgeons consider their own health when choosing a surgical modality.

    View details for DOI 10.1007/s11701-011-0330-3

    View details for PubMedID 27637981

  • The Role of Unconscious Bias in Surgical Safety and Outcomes SURGICAL CLINICS OF NORTH AMERICA Santry, H. P., Wren, S. M. 2012; 92 (1): 137-?


    Racial, ethnic, and gender disparities in health outcomes are a major challenge for the US health care system. Although the causes of these disparities are multifactorial, unconscious bias on the part of health care providers plays a role. Unconscious bias occurs when subconscious prejudicial beliefs about stereotypical individual attributes result in an automatic and unconscious reaction and/or behavior based on those beliefs. This article reviews the evidence in support of unconscious bias and resultant disparate health outcomes. Although unconscious bias cannot be entirely eliminated, acknowledging it, encouraging empathy, and understanding patients' sociocultural context promotes just, equitable, and compassionate care to all patients.

    View details for DOI 10.1016/j.suc.2011.11.006

    View details for Web of Science ID 000301157800014

    View details for PubMedID 22269267

  • Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Gould, M. K., Garcia, D. A., Wren, S. M., Karanicolas, P. J., Arcelus, J. I., Heit, J. A., Samama, C. M. 2012; 141 (2): e227S-77S


    VTE is a common cause of preventable death in surgical patients.We developed recommendations for thromboprophylaxis in nonorthopedic surgical patients by using systematic methods as described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.We describe several alternatives for stratifying the risk of VTE in general and abdominal-pelvic surgical patients. When the risk for VTE is very low (< 0.5%), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation. For patients at low risk for VTE (∼1.5%), we suggest mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC), over no prophylaxis (Grade 2C). For patients at moderate risk for VTE (∼3%) who are not at high risk for major bleeding complications, we suggest low-molecular-weight heparin (LMWH) (Grade 2B), low-dose unfractionated heparin (Grade 2B), or mechanical prophylaxis with IPC (Grade 2C) over no prophylaxis. For patients at high risk for VTE (∼6%) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis. In these patients, we suggest adding mechanical prophylaxis with elastic stockings or IPC to pharmacologic prophylaxis (Grade 2C). For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer, we recommend extended-duration, postoperative, pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B). For patients at moderate to high risk for VTE who are at high risk for major bleeding complications or those in whom the consequences of bleeding are believed to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C). For patients in all risk groups, we suggest that an inferior vena cava filter not be used for primary VTE prevention (Grade 2C) and that surveillance with venous compression ultrasonography should not be performed (Grade 2C). We developed similar recommendations for other nonorthopedic surgical populations.Optimal thromboprophylaxis in nonorthopedic surgical patients will consider the risks of VTE and bleeding complications as well as the values and preferences of individual patients.

    View details for DOI 10.1378/chest.11-2297

    View details for PubMedID 22315263

    View details for PubMedCentralID PMC3278061

  • Racial and ethnic differences in lymph node examination after colon cancer resection do not completely explain disparities in mortality CANCER Rhoads, K. F., Cullen, J., Ngo, J. V., Wren, S. M. 2012; 118 (2): 469-477


    In 1999, a multidisciplinary panel of experts in colorectal cancer reviewed the relevant medical literature and issued a consensus recommendation for a 12-lymph node (LN) minimum examination after resection for colon cancer. Some authors have shown racial/ethnic differences in receipt of this evidence-based care. To date, however, none has investigated the correlation between disparities in LN examination and disparities in outcomes after colon cancer treatment.This retrospective analysis used California Cancer Registry linked to California Office of Statewide Health Planning and Development discharge data (1996-2006). Chi-square analysis, logistic regression, and Cox proportional hazard models predicted disparities in receipt of an adequate examination and the effect of an inadequate exam on mortality and disparities. Patients with stage I and II colon cancers undergoing surgery in California were included; patients with stage III and IV disease were excluded.A total of 37,911 records were analyzed. Adequate staging occurred in fewer than half of cases. An inadequate examination (<12 LNs) was associated with higher mortality rates. Hispanics had the lowest odds of receiving an adequate exam; however, blacks, not Hispanics, had the highest risk of mortality compared with whites. This disparity was not completely explained by inadequate LN examination.Inadequate LN exam occurs often and is associated with increased mortality. There are disparities in receipt of the minimum exam, but this only explains a small part of the observed disparity in mortality. Improving the quality of LN examination alone is unlikely to correct colon cancer disparities.

    View details for DOI 10.1002/cncr.26316

    View details for Web of Science ID 000298846600025

    View details for PubMedID 21751191

  • Innovative leadership of casualty care: comment on "Eliminating preventable death on the battlefield". Archives of surgery Wren, S. M. 2011; 146 (12): 1358-?

    View details for DOI 10.1001/archsurg.2011.282

    View details for PubMedID 22184292

  • Solitary metastatic clear cell carcinoma to the spleen. Rare tumors Zayed, M. A., Kosek, J., Wren, S. M. 2011; 3 (4)


    A 57-year-old with a 9-year history of increased abdominal girth, presented with increased abdominal pain, anemia, and acute renal failure. His past medical history was only remarkable for a previous lung cancer 21 years ago that was treated with a right upper lung lobectomy. A computed tomography (CT) scan of the patient's abdomen showed a solitary 20×20×25cm cystic splenic mass. The patient underwent an urgent splenectomy. Intra-operatively a large splenic cystic cavity was found with a solid inferior splenic mass. An exhaustive histological analysis of the splenic mass confirmed a clear cell carcinoma with low malignant potential that likely represented a metastatic lesion from the patient's previous distant lung cancer. Postoperatively the patient recovered well and at 1-year followup the patient demonstrated no further evidence of metastatic disease. This case is extremely unique and provides a very rare example of a metastatic solitary clear cell carcinoma to the spleen, with a presumed latency period of more than 20 years.

    View details for DOI 10.4081/rt.2011.e43

    View details for PubMedID 22355498

  • Single-Port Robotic Cholecystectomy Results From a First Human Use Clinical Study of the New da Vinci Single-Site Surgical Platform ARCHIVES OF SURGERY Wren, S. M., Curet, M. J. 2011; 146 (10): 1122-1127


    To report our results from a first human use clinical study with the da Vinci Surgical single-site instrumentation in patients with gallbladder disease and to perform a retrospective comparison with traditional multiport laparoscopic cholecystectomy.Ten patients underwent robotic single-port cholecystectomy performed with the da Vinci Si robot and novel da Vinci single-site instrumentation. Outcomes and operative times were compared with patients undergoing traditional multiport laparoscopic cholecystectomy during the same period.Tertiary care Veterans Administration hospital.Outpatients older than 18 years with an American Society of Anesthesiologists class of 1 to 3, no prior upper abdominal surgery, and diagnosis of noninflammatory biliary disease.Single-site robotic cholecystectomy.Operative time, complications up to 30 days, pain scores, and overall satisfaction.Nine of 10 patients had completion of robotic single-site cholecystectomy. Average operating room time was 105.3 minutes compared with an average of 106.1 minutes in the standard laparoscopic group. There were no serious adverse events in the robotic surgery group, with an average follow-up of 3 or more months.Robotic single-port cholecystectomy is feasible and comparable with standard laparoscopic cholecystectomy in the Veterans Administration medical center setting.

    View details for DOI 10.1001/archsurg.2011.143

    View details for Web of Science ID 000295942300002

    View details for PubMedID 21690436

  • Multimedia manuscript. Endoscopic clipping of a post-Whipple pancreatic bleed. Surgical endoscopy Kaltenbach, T., Wren, S., Schumacher, L., Soetikno, R. 2009; 23 (9): 2159-2160


    Bleeding after pancreaticoduodenectomy most often occurs from the gastro- or duodeno-jejunal anastomosis. Bleeding at the pancreatic surface would be the most difficult to treat because it typically requires surgical resection of the pancreatic remnant-a surgery that has significant morbidity and mortality. Data that describe the role of endoscopy in the management of pancreaticojejunostomy bleeding are limited.We present the case of a 69-year-old man who had massive upper gastrointestinal bleeding on postoperative day 2 after a pyloric sparing Whipple procedure for cholangiocarcinoma. We endoscopically approached this massive upper gastrointestinal bleed by understanding the postsurgical anatomy to consider all of the potential bleeding sources: duodenojejunostomy, hepaticojejunstomy, and the pancreaticojejunostomy. Using a pediatric colonoscope with water jet capabilities, active bleeding could be seen originating from the cut pancreatic surface. Complete hemostasis was achieved after placement of two clips. We clipped again two clays later due to a minor rebleeding episode. We repeated endoscopy on postoperative day 6 for surveillance of the site. All clips were in place and there was no evidence of bleeding. The patient did well without recurrent bleeding and was discharged home on postoperative day 7. Six-month follow-up showed no recurrent bleeding episodes or development of fistulas.Endoscopic treatment of a bleeding site on the pancreatic surface of a pancreaticojejunostomy can be successful during the immediate postoperative period. Such an attempt at endoscopic hemostasis may prevent the need for completion pancreatectomy.

    View details for DOI 10.1007/s00464-009-0357-y

    View details for PubMedID 19277780

  • Endoscopic clipping of a post-whipple pancreatic bleed SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Kaltenbach, T., Wren, S., Schumacher, L., Soetikno, R. 2009; 23 (9): 2159-2160
  • Male Patients Above Age 60 have as Good Outcomes as Male Patients 50-59 Years Old at 1-Year Follow-up After Bariatric Surgery OBESITY SURGERY Wool, D., Bellatorre, N., Wren, S., Eisenberg, D. 2009; 19 (1): 18-21


    It is estimated that 25% of Americans older than 60 years are obese. Male gender and advanced age are indicators of increased risk for bariatric surgery. Good results have been shown in patients older than 50, but nearly all published studies include a large majority of females, and few include patients >60 years old. In this study, we examined the results of males over 60 years old.We reviewed a prospective database of 107 consecutive patients who underwent bariatric surgery between April 2002 and June 2007 at the Palo Alto VA. Of these, 60 patients were males older than 50 and available for follow-up 12 months postoperatively. There were 47 males 50-59 years old (group I) and 13 males older than 60 years (group II). Data were analyzed using Student's t test.Mean preoperative body mass index was similar in both groups (49.4 vs. 47.5 kg/m(2); p = 0.468). Length of hospital stay was similar (3.2 vs. 3.5 days; p = 0.678), but early morbidity was higher in group II patients (30.8% vs. 8.5%; p = 0.037). Morbidity included urinary tract infection, cardiac arrhythmias, and early bowel obstruction. Excess weight loss after 1 year was not significantly different (63.6% vs. 60.6%; p = 0.565). Diabetes resolution or improvement was seen in 87% of group I patients and 90% of group II patients.Despite a higher early morbidity rate, obese males >/=60 years old perform as well as male patients 50-59 years old with respect to excess weight loss, mortality, length of stay, and improvement of diabetes, at 1 year postoperatively.

    View details for DOI 10.1007/s11695-008-9734-1

    View details for Web of Science ID 000262281700004

    View details for PubMedID 18855082

  • Metastatic colon adenocarcinoma mimicking herpes zoster JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Goodwin, T. L., Wren, S. M. 2007; 205 (4): 625-625
  • Care within a Veterans Hospital - Earlier detection of colon cancer SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES van Roessel, P., Rouse, R. V., Wren, S. M. 2007; 21 (8): 1434-1440


    In 1998 the Veterans Administration mandated an externally monitored targeted colon cancer screening rate that was expected to result in earlier cancer detection and improved patient survival. The effectiveness of the protocol was evaluated in a retrospective case series at a tertiary care Veterans Administration Hospital that included all patients with the diagnosis of colon cancer between 1991 and 2003.Tumor stage, tumor location, and patient survival data were recorded and compared to National Cancer Data Base (NCDB) benchmarks.The study facility had a greater percentage of early cancers and fewer later stage cancers than the NCDB benchmark. Overall survival was better for the VA cohort compared to NCDB (all-cause 5-year survival: VA, 0.72; NCDB, 0.47. p < or = .001).The VA facility had a significantly greater percentage of early cancers and fewer stage III or IV cancers compared to a national benchmark and significantly improved survival compared to the national benchmark.

    View details for DOI 10.1007/s00464-006-9184-6

    View details for Web of Science ID 000248737700035

    View details for PubMedID 17294311

  • Transnasal small-caliber esophagogastroduodenoscopy for preoperative evaluation of the high-risk morbidly obese patient SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Alami, R. S., Schuster, R., Friedland, S., Curet, M. J., Wren, S. M., Soetikno, R., Morton, J. M., Safadi, B. Y. 2007; 21 (5): 758-760


    Esophagogastroduodenoscopy (EGD) is an important facet of the preoperative evaluation for bariatric surgery. Morbidly obese patients are at high risk for airway complications during this procedure, and an attractive alternative is transnasal EGD. This report describes a series of patients evaluated successfully using this technique.All patients undergoing preoperative transnasal small-caliber EGD for morbid obesity surgery between September 2004 and June 2005 at a Veterans Affairs Hospital were included in the analysis. The variables assessed were the adequacy of the examination, patient tolerance, the need for sedation, and the ability to perform interventions.The study enrolled 25 patients (17 men and 8 women) with an average age of 55 years (range, 44-63 years) and an average body mass index (BMI) of 47 kg/m2 (range, 38-69 kg/m2). All the patients met the 1991 National Institutes of Health (NIH) Consensus Conference Criteria for bariatric surgery and were undergoing preoperative evaluation. The most common comorbidities were hypertension (82%), diabetes mellitus (80%), and obstructive sleep apnea (68%). All 25 patients had successful cannulation of the duodenum's second portion with excellent tolerance. There were no sedation requirements for 23 (92%) of the 25 patients. Significant pathology was found in 14 (56%) of the 25 patients, including hiatal hernia (28%), gastritis (16%), esophageal intestinal metaplasia (16%), esophagitis (12%), gastric polyps (8%), gastric ulcer (4%) and esophageal varices (4%). Biopsies were indicated for 12 patients and successful for all 12 (100%).Transnasal small-caliber EGD is a feasible and safe alternative to conventional EGD for the preoperative evaluation of patients undergoing bariatric surgery. It requires minimal to no sedation in a population at high risk for complications in this setting. In addition, this technique is effective in identifying pathology that requires preoperative treatment and offers a complete examination with biopsy capabilities. This technique should be considered for all morbidly obese patients at high risk for airway compromise during EGD.

    View details for DOI 10.1007/s00464-006-9101-z

    View details for Web of Science ID 000246351800013

    View details for PubMedID 17235723

  • Short- and long-term outcomes of standardized EMR of nonpolypoid (flat and depressed) colorectal lesions >= 1 cm (with video) GASTROINTESTINAL ENDOSCOPY Kaltenbach, T., Friedland, S., Maheshwari, A., Ouyang, D., Rouse, R. V., Wren, S., Soetikno, R. 2007; 65 (6): 857-865


    Nonpolypoid (flat and depressed) colorectal lesions are increasingly recognized. Their endoscopic removal requires specialized EMR techniques, which are more complex to perform. Outcomes data on EMR of nonpolypoid neoplasms in the United States is needed.To determine the safety and efficacy of EMR in the resection of nonpolypoid colorectal neoplasms > or = 1 cm.Retrospective analysis.Veterans Affairs Palo Alto Health Care System.Over a 5-year period, patients who underwent EMR for nonpolypoid colorectal lesions > or = 1 cm.A standardized approach that included lesion assessment, classification, inject-and-cut EMR technique, reassessment, and treatment of residual tissue.Complete resection, bleeding, perforation, development of advanced cancer, and death.A total of 100 patients (125 lesions: 117 flat and 8 depressed) met inclusion criteria. Mean size was 16.7 +/- 7 mm (range, 10-50 mm). Histology included 5 submucosal invasive cancers, 5 carcinomas in situ, and 91 adenomas. Thirty-eight patients (48 lesions) did not receive surveillance colonoscopy: 8 had surgery, 16 had hyperplastic pathology, and 14 did not undergo repeat examination. Surveillance colonoscopy was performed on 62 patients (77 lesions). Complete resection was achieved in 100% of these patients after 1 to 3 surveillance colonoscopies. All patients received follow-up (mean [standard deviation] = 4.5 +/- 1.4 years); none developed colorectal cancer or metastasis.Single endoscopist, retrospective study.A standardized EMR (inject-and-cut) technique is a safe and curative treatment option in nonpolypoid colorectal neoplasms (> or = 1 cm) in the United States.

    View details for DOI 10.1016/j.gie.2006.11.035

    View details for Web of Science ID 000246217300017

    View details for PubMedID 17466205

  • The use of acellular dermal matrix for contaminated abdominal wall defects: wound status predicts success 30th Annual Surgical Symposium of the Association-of-VA-Surgeons Schuster, R., Singh, J., Safadi, B. Y., Wren, S. M. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2006: 594–97


    Contaminated abdominal wall fascial defects present a challenging problem. The use of human acellular dermal matrix (AlloDerm; LifeCell Corp., Branchburg, NJ) provides a novel method of primary closure of abdominal wall defects in this setting. The aim of the current study was to determine what factors predicted fascial wall failure as determined by the presence of hernia on follow-up exam after AlloDerm placement.All patients who underwent surgery for contaminated abdominal wall fascial defects with placement of AlloDerm from June 2003 to September 2005 at a tertiary care Veterans Affairs hospital were included in the analysis. Patients were followed until hernia recurrence or last clinic visit.Eighteen patients had AlloDerm placed for contaminated fascial defects and all were included in the analysis. Primary wound closure was performed on 12/18 (67%) patients, with 6/18 (33%) patients initially left with open wounds. Patients with open wounds were treated with wound vacuum-assisted closure (VAC) devices (4/6) or saline dressings (2/6). Overall ventral hernia recurrence rate was 50% (9/18) with an average follow up of 9.1 months. Patients who had primary wound closure at the completion of the operation had a 33% (4/12) recurrence rate. Patients who did not have primary wound closure had an 83.3% (5/6) recurrence rate. The significant difference shows (P = .03) that open wound status predicts recurrence. The average size of AlloDerm sheets used was 164.0 cm2 in the closed group and 146.2 cm2 in the primary open wound group (P = .64). Average cost per patient was 4680 dollars for AlloDerm.These data suggest that an open wound in the postoperative period after AlloDerm placement for treatment of contaminated fascial defects is associated with a high probability of hernia recurrence. Our data do not support the use of this expensive material unless there is a good chance of having a closed wound.

    View details for DOI 10.1016/j.amjsurg.2006.08.017

    View details for Web of Science ID 000241820000007

    View details for PubMedID 17071190

  • Concurrent gastric bypass and repair of anterior abdominal wall hernias OBESITY SURGERY Schuster, R., Curet, M. J., Alami, R. S., Morton, J. M., Wren, S. M., Safadi, B. Y. 2006; 16 (9): 1205-1208


    Many patients seeking surgical treatment for morbid obesity present with anterior abdominal wall hernias. Although principles of hernia repair involve a tension-free repair with the use of prosthetic mesh, there is concern about the use of mesh in gastric bypass surgery due to potential contamination with the contents of the gastrointestinal tract and resultant mesh infection. We report our series of patients undergoing Roux-en-Y gastric bypass (RYGBP) and simultaneous anterior abdominal wall hernia repair.All patients who underwent simultaneous RYGBP surgery and anterior abdominal wall hernia repair were reviewed.12 patients underwent concurrent RYGBP and anterior wall hernia repair. There were 5 women and 7 men with average age 54.9 +/- 8.5 years (range 35 to 64) and average body mass index (BMI) 50.4 +/- 10.3 kg/m(2) (range 38 to 70). Two open and 10 laparoscopic RYGBP operations were performed. Nine patients (75%) underwent incisional hernia repairs and 3 patients (25%) underwent umbilical hernia repair concurrent with gastric bypass. Average size of defect was 14.7 +/- 13.4 cm(2). One patient had primary repair and 11 patients had prosthetic mesh repair: polypropylene in 3 patients (25%) and polyester in 8 patients (67%). With a 14.1 +/- 9.3 month follow-up, there have been no mesh infections and 2 recurrences, one in the patient who underwent primary repair and one in a patient repaired with polyester mesh but with two previous failed incisional hernia repairs.Concurrent RYGBP and repair of anterior abdominal wall hernias is safe and feasible. In order to optimize success, tension-free principles of hernia repair with the use of prosthetic mesh should be followed since no mesh infections occurred in our series.

    View details for Web of Science ID 000240355400015

    View details for PubMedID 16989705

  • Laparoscopic Roux-en-Y gastric bypass at a Veterans Affairs and high-volume academic facilities: a comparison of institutional outcomes 29th Annual Surgical Symposium of the Association-of-VA-Surgeons Alami, R. S., Morton, J. M., Sanchez, B. R., Curet, M. J., Wren, S. M., Safadi, B. Y. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2005: 821–25


    Outcomes of bariatric surgery have been linked to institutional case volume. The objective of our study was to compare outcome of laparoscopic Roux-en-y gastric bypass (RYGB) in 2 settings: a low-volume Veterans Affairs (VA) and a high-volume university hospital (UH).Over a period of 27 months, 140 patients underwent RYGB (137 laparoscopic, 3 open) performed by 1 surgeon. Fifty-five were performed at a VA and 85 at a UH with an annual caseload close to 300.The body mass index in both groups was similar, but patients at the VA were older, mostly men, and more likely to have hypertension (HTN), obstructive sleep apnea, and diabetes mellitus (DM). Operative and anesthesia times were significantly longer at the VA. There were no differences in 30-day mortality (none), major morbidity, conversion rates, or reoperation rates.Laparoscopic RYGB can be performed safely at a VA facility despite a higher risk population and low annual volume.

    View details for DOI 10.1016/j.amjsurg.2005.07.027

    View details for Web of Science ID 000232935200030

    View details for PubMedID 16226965

  • Preoperative oral antibiotics in colorectal surgery increase the rate of Clostridium difficile colitis 76th Annual Meeting of the Pacific-Coast-Surgical-Association Wren, S. M., Ahmed, N., Jamal, A., Safadi, B. Y. AMER MEDICAL ASSOC. 2005: 752–55


    Bowel preparation traditionally consists of cathartics, oral antibiotics, and intravenous antibiotics. We hypothesize that the use of oral antibiotics in bowel preparation results in a higher rate of postoperative Clostridium difficile colitis.Retrospective case-controlled study of elective colon surgery patients; January 1997 to June 2003.Tertiary care veterans administration hospital.Records of patients who underwent elective colorectal surgery (n = 304) were reviewed. Patients with bowel obstruction or emergent operation were excluded.Detection of C difficile toxin A/B by enzyme-linked immunosorbent assay in a stool specimen within 30 days of surgery.All 304 patients received both cathartics and intravenous antibiotics. Of 304 patients, 107 (35.1%) received oral antibiotics. The rate of postoperative C difficile colitis was 4.2% in the entire study population. The rate of C difficile infection was higher in patients who received oral antibiotics (7.4%) compared with patients who did not receive oral antibiotics (2.6%; P = .03). There were no C difficile-related mortalities.Oral nonabsorbable antibiotics in bowel preparation resulted in a higher rate of C difficile infection. This may be due to the additional effect of oral antibiotics on normal bowel flora. We recommend that oral nonabsorbable antibiotics not be used in preoperative bowel preparation regimens since postoperative C difficile infection can lead to additional morbidity, length of stay, and hospital costs.

    View details for Web of Science ID 000230948300009

    View details for PubMedID 16103284

  • Comparison of training on two laparoscopic simulators and assessment of skills transfer to surgical performance JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Youngblood, P. L., Srivastava, S., Curet, M., Heinrichs, W. L., Dev, P., Wren, S. M. 2005; 200 (4): 546-551


    Several studies have investigated the transfer of surgical trainees' skills acquired on surgical simulators to the operating room setting. The purpose of this study was to compare the effectiveness of two laparoscopic surgery simulators by assessing the transfer of skills learned on simulators to closely matched surgical tasks in the animal laboratory.In this post-test-only Control group study design, 46 surgically naive medical student volunteers were randomly assigned to one of three groups: Tower Trainer group (n = 16), LapSim group (n = 17), and Control group (n = 13). Outcomes measures included both time and accuracy scores on three laparoscopic tasks (Task 1: Grasp and Place; Task 2: Run the Bowel; Task 3: Clip and Cut) performed on live anesthetized pigs, and a global rating of overall performance as judged by four experienced surgeons.The Tower Trainer group performed significantly better than the Control group on 1 of 7 outcomes measures-Task 3: Time (p < 0.032), although the LapSim group performed significantly better than the Control group on 2 of 7 measures-Task 3: Time (p < 0.008) and Global score (p < 0.005). In comparing the two simulators, the LapSim group performed significantly better than the Tower Trainer group on 3 of 7 outcomes measures-Task 2: Time (p < 0.032), Task 2: Accuracy (p < 0.030) and Global score (p < 0.005), although the Tower Trainer group did not perform significantly better than the LapSim group on any measure.This study demonstrated that naive subjects trained on a virtual-reality part-task trainer performed better on live surgical tasks in a porcine model as compared with those trained with a traditional box trainer. These findings could aid in selection of appropriate training methodologies.

    View details for DOI 10.1016/j.jamcollsurg.2004.11.011

    View details for Web of Science ID 000228085200007

    View details for PubMedID 15804468

  • Introducing laparoscopic Roux-en-Y gastric bypass at a Veterans Affairs medical facility 28th Annual Surgical Symposium of the Association-of-VA-Surgeons Safadi, B. Y., Kieran, J. A., Hall, R. G., Morton, J. M., Bellatorre, N., Shinoda, E., Johnson, P. J., Curet, M. J., Wren, S. M. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2004: 606–10


    Previous studies have shown that advanced age, diabetes, and male gender are associated with higher morbidity and mortality after bariatric surgery. Those risk factors are characteristic of patients in the Veterans Affairs (VA) health care system. Laparoscopic Roux-en-Y gastric bypass (RYGB) has become an established treatment modality for morbid obesity. Our objective was to review the initial experience with laparoscopic (RYGB) for morbid obesity at our VA facility.A retrospective review was used.Between May of 2002 and April of 2004, 40 patients underwent laparoscopic RYGB. All patients met National Institutes of Health consensus statement guidelines for bariatric surgery. There were 30 (75%) male and 10 (25%) female patients, with an average age of 49.9 +/- 8.7 years and an average body mass index (BMI) of 48.1 +/- 8.5 kg/m(2). Preoperative comorbidities included diabetes mellitus (DM) in 59%, hypertension in 79%, and obstructive sleep apnea in 74.4%. The procedure was converted to an open procedure in 3 patients (7.5%). There were no mortalities. Immediate (within 30 days) complications developed in 9 (22.5%) patients, necessitating abdominal re-operation in 3 patients (7.5%). The median length of hospital stay was 3 days. Late complications (>30 days) developed in 8 (20%) patients. Percent excess weight loss at 3, 6, and 12 months was 44% (n = 34), 59% (n = 29), and 70.0% (n = 22), respectively. In 23 patients who were followed-up for more than 3 months, DM resolved in 79% and improved in 21% at a mean follow-up evaluation of 13 months.Laparoscopic RYGB can be performed with acceptable morbidity and with good short-term results in a VA hospital setting. Morbid obesity is prevalent in the VA patient population and access to bariatric surgery should be an available alternative.

    View details for DOI 10.1016/j.amjsurg.2004.07.021

    View details for Web of Science ID 000225208600032

    View details for PubMedID 15546580

  • Institutional commitment to rectal cancer screening results in earlier-stage cancers on diagnosis ANNALS OF SURGICAL ONCOLOGY Battat, A. C., Rouse, R. V., Dempsey, L., Safadi, B. Y., Wren, S. M. 2004; 11 (11): 970-976


    The Veterans Administration hospitals underwent an institutional directive in 1998 to meet a colorectal cancer screening (CRCS) standard. This intervention should result in an increase in the hospital's screening rate and percentage of early-stage rectal cancers diagnosed.A retrospective review, from 1991 to 2002, of our institution's pathology and cancer registry databases for rectal cancers. CRCS data were obtained from the Veterans Administration Prevention Disease Index. Cancer stage at diagnosis was compared before and after the directive and was compared with the National Cancer Data Base and the Surveillance, Epidemiology, and End Results data.The rate of CRCS was 55% in 1998 and increased to 75% in 2003. During the 11 years studied, a total of 147 rectal cancers were diagnosed. After the Veterans Administration directive, there was a significant increase in stage 0 cancers (P < .02) and an overall migration to earlier-stage cancers. Our Veterans Administration hospital had a significantly greater percentage of stage 0 cancers both before (P < .007) and after the directive (P < .00) and had fewer stage 3 cancers after the directive (P < .03) compared with National Cancer Data Base data. Compared with Surveillance, Epidemiology, and End Results data, the Palo Alto Veterans Affairs Health Care System had more local disease (P < .03) and less regional disease (P < .006).These data suggest that a monitored institutional directive may significantly increase early detection of rectal cancers. This should result in a greater survival rate and lower local recurrence rate, because survival is predicated on stage at presentation. This may serve as a model for other health-care systems.

    View details for DOI 10.1245/ASO.2004.03.047

    View details for Web of Science ID 000224781300006

    View details for PubMedID 15525825

  • Utilization of laparoscopic antireflux surgery at a single Veterans Affairs facility compared with the Veterans Affairs national trend 27th Annual Surgical Symposium of the Association-of-VA-Surgeons Safadi, B. Y., Kown, M., Wren, S. EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. 2003: 505–8


    The widespread use of laparoscopy in the early 1990s has led to an increase in the utilization of antireflux procedures for the treatment of gastroesophageal reflux disease (GERD). This trend has been observed in the private sector, but not within the Department of Veterans Affairs (VA) health care system. Published data suggest that among patients undergoing antireflux surgical procedures, those in the VA were less likely than those in the private sector to undergo laparoscopic surgery. The objective of this study was to determine the trend in the use of laparoscopic antireflux surgical procedures at our VA facility and compare it with the national VA trend.All antireflux operations performed at our VA facility from 1991 to 2002 were recorded along with techniques used. National VA data on the utilization of antireflux procedures from 1991 to 1999 was extracted from a recent publication by Finlayson et al.In contrast to the trend observed nationally across VA hospitals, the rate of utilization of antireflux surgery at our VA facility has increased compared with baseline in 1991. Of 83 fundoplications performed from 1991 to 2002, 76 (92%) were attempted or completed laparoscopically. The conversion rate from laparoscopic to open approach was 6.6%.We have observed an increase in the utilization of antireflux surgery since 1991 at our VA facility. In addition, most fundoplications were performed laparoscopically. These findings are in contrast to published national VA data. The presence of surgeons with interest in laparoscopy, institutional support, and a dedicated esophageal function laboratory may explain these findings.

    View details for DOI 10.1016/j.amjsurg.2003.07.025

    View details for Web of Science ID 000186307300017

    View details for PubMedID 14599615

  • A novel technique to treat ruptured umbilical hernias in patients with liver cirrhosis and severe ascites JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES-PART A Melcher, M. L., Lobato, R. L., Wren, S. M. 2003; 13 (5): 331-332


    The full-thickness skin erosion (rupture) of an umbilical hernia in a patient with end-stage liver disease can lead to significant morbidity and mortality. Here, we present a case report of the use of a novel technique to treat a patient with this condition. The use of a fibrin-based tissue adhesive provides a means of managing such patients medically.

    View details for Web of Science ID 000185762400011

    View details for PubMedID 14617394

  • Positron emission tomography in the initial staging of esophageal cancer 73rd Annual Meeting of the Pacific-Coast-Surgical-Association Wren, S. M., Stijns, P., Srinivas, S. AMER MEDICAL ASSOC. 2002: 1001–6


    To assess the value of positron emission tomography (PET) compared with computed tomography (CT) in the initial staging of esophageal cancer.Case series.Tertiary care veterans hospital.Patients with newly diagnosed esophageal cancers from January 1996 through May 2001 who underwent both CT and PET scanning within 4 weeks were included in the study (n = 24). Only patients who underwent pathological or radiographic follow-up were included.The sensitivity, specificity, and negative and positive predictive values of CT and PET were determined based on a criterion standard of pathological staging in 16 patients (67%) and follow-up imaging in 8 patients (33%).For staging regional lymph node involvement, CT and PET scans showed no statistically significant difference in sensitivity (57% and 71%, respectively) and specificity (71% and 86%, respectively). For detection of metastatic disease, CT and PET showed no significant difference in sensitivity (83% and 67%, respectively) and specificity (75% and 92%, respectively). There was no significant difference in clinical decision making when the results of both tests were discordant.There was no significant difference between the 2 imaging modalities in the initial staging of esophageal cancer. The CT scan was a sensitive indicator of distant metastases, whereas PET was more specific. It is unclear what additional role PET scanning should have in the initial screening of patients.

    View details for Web of Science ID 000177920800004

    View details for PubMedID 12215149

  • Effective management of bleeding during tumor resection with a collagen-based hemostatic agent AMERICAN SURGEON Chapman, W. C., Wren, S. M., LEBOVIC, G. S., Malawer, M., Sherman, R., Block, J. E. 2002; 68 (9): 802-807


    In a prospective controlled trial hemostatic effectiveness of a novel collagen-based composite (CoStasis) was compared with a collagen sponge applied with manual pressure at diffusely bleeding sites after surgical tumor resection. The proportion of subjects achieving complete cessation of bleeding within 10 minutes (i.e., hemostatic success) and the time to "complete hemostasis" were determined at raw surgical sites after tumor resection among 23 experimental and 30 control subjects. There was a similar distribution in tumor types (e.g., benign vs malignant) evaluated between treatment groups. A significantly greater proportion of experimental subjects achieved complete hemostasis within 10 minutes of observation compared with controls [23 of 23 (100%) vs 21 of 30 (70%); P = 0.003]. The median time required to achieve complete hemostasis was more than three times longer for subjects treated with the collagen sponge compared with subjects treated with CoStasis (243 vs 78 seconds; P = 0.0001). Approximately 80 per cent of experimental subjects achieved complete hemostasis within 2 minutes compared with only 35 per cent of controls. There were no adverse events related to the experimental treatment in this study. These results support the use of this novel hemostatic agent to control diffuse surgical site bleeding after tumor resection at diverse anatomical locations.

    View details for Web of Science ID 000181916500015

    View details for PubMedID 12356154

  • Intravascular hemolysis from a Clostridium perfringens liver abscess JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS Kreidl, K. O., Green, G. R., Wren, S. M. 2002; 194 (3): 387-387

    View details for Web of Science ID 000174231900014

    View details for PubMedID 11893140

  • Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES Shetler, K., Nieuwenhuis, R., Wren, S. M., Triadafilopoulos, G. 2001; 15 (7): 653-659


    We explored the potential of early decompressive colonoscopy with intracolonic vancomycin administration as an adjunctive therapy for severe pseudomembranous Clostridium difficile colitis with ileus and toxic megacolon.We reviewed the symptoms, signs, laboratory tests, radiographic findings, and outcomes from the medical records of seven patients who experienced eight episodes of severe pseudomembranous colitis with ileus and toxic megacolon. All seven patients underwent decompressive colonoscopy with intracolonic perfusion of vancomycin.Fever, abdominal pain, diarrhea, abdominal distention, and tenderness were present in all patients. Five of seven patients were comatose, obtunded, or confused, and six of the seven required ventilatory support. The white blood cell count was greater than 16,000 in seven cases (six patients). Colonoscopy showed left-side pseudomembranous colitis in one patient, right-side colitis in one patient, and diffuse pseudomembranous pancolitis in five patients. Two patients were discharged with improvement. Five patients had numerous medical problems leading to their death. Complete resolution of pseudomembranous colitis occurred in four patients. One patient had a partial response, and two patients failed therapy.Colonoscopic decompression and intracolonic vancomycin administration in the management of severe, acute, pseudomembranous colitis associated with ileus and toxic megacolon is feasible, safe, and effective in approximately 57% to 71% of cases.

    View details for Web of Science ID 000169664100006

    View details for PubMedID 11591962

  • Results of a screening program for prostate cancer in patients scheduled for abdominoperineal resection for colorectal pathologic findings UROLOGY Terris, M. K., Wren, S. M. 2001; 57 (5): 943-945


    Because of the difficulty of accessing the prostate for tissue sampling after surgical removal of the rectum and obliteration of the anus, we started an early detection program for prostate cancer in all men scheduled for abdominoperineal resection.Twenty consecutive men were screened for prostatic adenocarcinoma before planned abdominoperineal resection for colorectal pathologic findings. Patients were 48 to 77 years old (mean 66.9). Screening included serum prostate-specific antigen determination and digital rectal examination. Those patients with suspicious findings underwent transrectal ultrasound-guided sextant biopsies of the prostate.One patient was excluded because of a prior history of prostate cancer. Six (31.6%) of the remaining 19 patients demonstrated elevated prostate-specific antigen levels (greater than 4.0 ng/mL); two of these patients also had an abnormal digital rectal examination. Transrectal ultrasound and prostate biopsies in these 6 patients revealed prostatic adenocarcinoma in 3 patients (50% of those undergoing biopsies or 15.8% of those screened). The 13 patients who did not undergo prostate biopsies had prostate-specific antigen levels from 0.4 to 2.4 ng/mL (mean 0.9) and normal prostate glands according to the digital rectal examinations.Screening for prostate cancer in men 50 years old or older with 10 years or longer life expectancy before they undergo abdominoperineal resection detects a significant number of prostatic malignancies and should be encouraged.

    View details for Web of Science ID 000168644300021

    View details for PubMedID 11337299

  • A novel collagen-based composite offers effective hemostasis for multiple surgical indications: Results of a randomized controlled trial SURGERY Chapman, W. C., Sherman, R., Boyce, S., Malawer, M., Hill, A., Buncke, G., Block, J. E., Fung, C. J., Clavien, P., Lee, K. F., LEBOVIC, G. S., Wren, S. M., Diethrich, E., Goldstein, R. 2001; 129 (4): 445-450


    Intraoperative bleeding is ubiquitous during open surgical procedures and uniformly effective hemostasis remains elusive. We conducted a randomized controlled trial to determine the effectiveness of a novel collagen-based composite (CoStasis Surgical Hemostat) compared with standard methods of hemostasis during general, hepatic, cardiac, and orthopedic operations.Hemostatic treatment was assigned randomly to 347 subjects; 318 subjects (167 CoStasis, 151 controls) underwent operation, received treatment, and provided hemostatic success data. CoStasis was applied to the bleeding site without manual pressure as a sprayable liquid composite of bovine microfibrillar collagen, bovine thrombin, and autologous plasma. Manual compression was used as the control hemostat. Hemostatic success was achieved if bleeding had ceased completely within 10 minutes (3 minutes for cardiac subjects). The time to controlled bleeding (ie, slight oozing) and time to complete hemostasis were recorded for all subjects.Hemostatic success was achieved in more than 90% (153/167) of CoStasis subjects compared with 58% (88/151) of control subjects (P =.01). Superior hemostatic effectiveness with CoStasis was realized in every surgical specialty: general (77/79 vs 49/75, P =.01), hepatic (38/39 vs 20/29, P =.01), cardiac (28/37 vs 17/37, P =.02), and orthopedic (10/12 vs 2/10, P =.01). The duration of bleeding was also significantly shorter with CoStasis. The median time to controlled bleeding (42 seconds vs 150 seconds, P =.0001) and time to complete hemostasis (75 seconds vs 252 seconds, P =.0001) were both markedly longer with the control intervention. There were no serious adverse events related to the use of CoStasis.CoStasis is more effective at controlling and stopping diffuse intraoperative bleeding than standard methods of hemostasis in 4 distinct surgical indications representing a wide variety of operative interventions.

    View details for Web of Science ID 000167986600010

    View details for PubMedID 11283536

  • External beam radiotherapy for synchronous rectal and prostatic tumors. Urology Siu, W., Kapp, D. S., Wren, S. M., King, C., Terris, M. K. 2001; 57 (4): 800-?


    Two patients were diagnosed with large rectal tumors and localized prostate cancer. The prostate-specific antigen level at diagnosis was 7.9 ng/mL and 9.0 ng/mL in the 2 patients. Knowledge of the presence of both tumors and their close proximity allowed creation of a modified three-dimensional conformal radiotherapy plan to treat both tumors. The patients had no evidence of rectal tumor recurrence and their prostate-specific antigen level was 0.5 ng/mL and 0.7 ng/mL at 1 and 2 years after therapy, respectively. We conclude that efficient, effective pelvic irradiation can be designed for synchronous rectal and prostate malignancies.

    View details for PubMedID 11306416

  • Does an infected peripancreatic fluid collection or abscess mandate operation? ANNALS OF SURGERY Baril, N. B., Ralls, P. W., Wren, S. M., Selby, R. R., Radin, R., Parekh, D., Jabbour, N., Stain, S. C. 2000; 231 (3): 361-367


    To assess the treatment of peripancreatic fluid collections or abscess with percutaneous catheter drainage (PCD).Surgical intervention has been the mainstay of treatment for infected peripancreatic fluid collections and abscesses. Increasingly, PCD has been used, with mixed results reported in the literature.A retrospective chart review of 1993 to 1997 was performed on 82 patients at a tertiary care public teaching hospital who had computed tomography-guided aspiration for suspected infected pancreatic fluid collection or abscess. Culture results, need for subsequent surgical intervention, length of stay, and death rate were assessed.One hundred thirty-five aspirations were performed in 82 patients (57 male patients, 25 female patients) with a mean age of 40 years (range 17-68). The etiologies were alcohol (41), gallstones (32), and other (9). The mean number of Ranson's criteria was four (range 0-9). All patients received antibiotics. Forty-eight patients had evidence of pancreatic necrosis on computed tomography scan. Cultures were negative in 40 patients and positive in 42. Twenty-five of the 42 culture-positive patients had PCD as primary therapy, and 6 required subsequent surgery. Eleven patients had primary surgical therapy, and five required subsequent surgery. Six patients were treated with only antibiotics. The death rates were 12% for culture-positive patients and 8% for the entire 82 patients.Historically, patients with positive peripancreatic aspirate culture have required operation. This series reports an evolving strategy of reliance on catheter drainage. PCD should be considered as the initial therapy for culture-positive patients, with surgical intervention reserved for patients in whom treatment fails.

    View details for Web of Science ID 000085635500009

    View details for PubMedID 10714629

  • Clinical and pathologic overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel AMERICAN JOURNAL OF SURGICAL PATHOLOGY Cortina, G., Wren, S., Armstrong, B., Lewin, K., Fajardo, L. 1999; 23 (11): 1414-1417


    Diaphragm disease (DD) is a radiographically subtle cause of small bowel obstruction and is part of the spectrum of diseases associated with nonsteroidal anti-inflammatory drug injury. The neuromuscular and vascular hamartoma (NMVH) is a nonepithelial hamartomatous, submucosally based proliferation of mature submucosal elements capable of causing small bowel obstruction. The authors report two patients in whom the clinical setting and gross pathology are that of DD, but the histologic characterization is identical to that described for NMVH. It is probable that in some patients the two diseases overlap so that some patients readily fit the criteria for both entities.

    View details for Web of Science ID 000083467900013

    View details for PubMedID 10555011

  • Antiviral cytotoxic activity across a species barrier in mixed xenogeneic chimeras: Functional restriction to host MHC JOURNAL OF IMMUNOLOGY Colson, Y. L., Tripp, R. A., Doherty, P. C., Wren, S. M., Neipp, M., El-Ezz, A. Y., Ildstad, S. T. 1998; 160 (8): 3790-3796


    Reconstitution of lethally irradiated mice with a mixture of mouse and rat bone marrow cells (mouse + rat-->mouse) results in mixed xenogeneic chimerism and donor-specific tolerance. The current study demonstrates that mouse and rat T lymphocytes that have developed in xenogeneic chimeras are restricted to Ag presentation by mouse, but not rat, APC. Restriction to host Ags results in functional immunocompetence with generation of antiviral cytotoxic activity in vivo, within and across species barriers. These data demonstrate for the first time that the host thymus is sufficient to support development and positive selection of functional cross-species T lymphocytes. The superior immunocompetence, as compared with fully xenogeneic (rat-->mouse) chimeras, may prove to be of significant benefit in the clinical application of xenotransplantation to solid organ transplantation and immune reconstitution for AIDS.

    View details for Web of Science ID 000072970400023

    View details for PubMedID 9558082

  • Is cryosurgical ablation appropriate for treating hepatocellular cancer? 104th Scientific Session of the Western-Surgical-Association Wren, S. M., Coburn, M. M., Tan, M., Daniels, J. R., Yassa, N., Carpenter, C. L., Stain, S. C. AMER MEDICAL ASSOC. 1997: 599–604


    To examine the feasibility and efficacy of cryosurgical ablation as treatment for patients with cirrhosis with unresectable hepatocellular carcinoma.Retrospective case series.A tertiary public hospital and a cancer center.Twelve patients with cirrhosis with hepatocellular carcinoma (stage II, 2; stage III, 1; stage IVA, 7; stage IVB, 2).Cryosurgical ablation of all identifiable tumors. Nine patients treated with curative intent were included in the survival analysis, and 3 were treated for palliation. Five patients were treated with preoperative intra-arterial chemoembolization.Perioperative complications and the effects of tumor stage and chemoembolization were examined. Patient survival and disease-free interval were calculated by life-table analysis.No perioperative deaths occurred and 1 patient had 2 postoperative complications: pneumonia and biloma. The mean survival has been 19 months after cryosurgical ablation and 29 months after diagnosis. Three of the 9 patients treated with curative intent died with recurrence at a mean of 17 months after cryosurgical ablation. Four patients are alive with recurrence at a mean of 19 months after cryosurgical ablation and 38 months after diagnosis. Two patients with stage II disease have no evidence of recurrence 10 and 32 months after cryosurgical ablation.Cryosurgical ablation is feasible and safe for treatment of hepatocellular carcinoma in patients with cirrhosis. The technique is primarily palliative but may provide a possibility of cure in patients with lower-stage disease.

    View details for Web of Science ID A1997XE52600008

    View details for PubMedID 9197851

  • Color flow sonography in evaluating the resectability of periampullary and pancreatic tumors JOURNAL OF ULTRASOUND IN MEDICINE Ralls, P. W., Wren, S. M., Radin, R., Stain, S. C., Yang, J., Parekh, D. 1997; 16 (2): 131-140


    Over the past several years, we have developed a technique to assess the resectability of periampullary and pancreatic tumors using color flow sonography. This is a feasibility study to determine if sonography with color flow imaging can play a role in evaluating patients with periampullary and pancreatic tumors. This study comprises a retrospective analysis of 51 patients referred for color flow sonographic evaluation of resectability of periampullary and pancreatic neoplasm. Scanning was performed with state-of-the-art color flow sonographic systems. Vessels that were touched or occluded by tumor were categorized according to a Pancreatic Color Doppler Score. Other factors affecting resectability (metastasis, enlarged nodes) were recorded. Sonographic findings were correlated with surgical resectability and pathologic findings regarding tumor margins. The color flow study was complete technically (all index vessels visualized) in 49 of 51 patients (96%). In all, 643 of 647 vessels (99.4%) were imaged. Forty-five patients had sufficient surgical, pathologic, or clinical proof to be included in the resectability analysis. All 18 patients with circumferential tumor or vascular occlusion (Pancreatic Color Doppler Score 4 and 5) were found to have unresectable disease. All 10 patients in whom tumor did not touch (Pancreatic Color Doppler Score 0) had negative margins. All 30 patients considered to have unresectable tumors sonographically could not be resected. Patients in this category had one or more of the following: positive pathologic margins, positive nodes, liver metastasis, or not clinically resectable. Six of 15 considered resectable sonographically (40%) were unresectable for cure. Surgeons believed that color flow sonography influenced management in 10 of 45 patients (22% overall). Color flow sonography, a painless, noninvasive, and relatively inexpensive examination, may be an effective screening tool to evaluate periampullary and pancreatic neoplasms for resectability. Our data show that color flow sonography can correctly predict unresectability of periampullary and pancreatic neoplasms. Any future evaluation of imaging and management of periampullary and pancreatic tumors should include color flow sonography.

    View details for Web of Science ID A1997XT74600009

    View details for PubMedID 9166806

  • The role of anticoagulation in pylephlebitis 48th Annual Meeting of the Southwestern Surgical Congress Baril, N., Wren, S., Radin, R., Ralls, P., Stain, S. CAHNERS PUBL CO. 1996: 449–53


    Pylephlebitis may complicate any intra-abdominal infection and carries a high mortality rate. Acute cases are usually anticoagulated to prevent thrombus extension and enteric ischemia; however, the role of anticoagulation has not been clearly defined.Over a 3-year period, pylephlebitis was diagnosed in 44 patients with portal vein thrombosis on computed tomography scan with fever, leukocytosis, and/or positive blood cultures. The charts were reviewed for etiology, extent of venous thrombosis, and method and results of treatment.Eighteen patients were hypercoagulable, due to clotting factor deficiencies (6), malignancy (8), or AIDS (4). Fifteen patients had mesenteric vein involvement. Thirty-two patients were not anticoagulated, and 5 died (3 with hypercoagulable states and 2 with normal clotting function). Twelve patients were anticoagulated, and none developed subsequent bowel infarction or died.Patients with pylephlebitis and a hypercoagulable state due to neoplasms or clotting factor deficiencies should be anticoagulated. Patients with normal clotting function and mesenteric vein involvement may also benefit. We believe anticoagulation in patients with thrombus isolated to the portal vein and normal clotting function may be unnecessary.

    View details for Web of Science ID A1996VR81800009

    View details for PubMedID 8942542

  • Selective management of hepatic adenomas Annual Meeting of the Southern-California-Chapter of the American-College-of-Surgeons Ault, G. T., Wren, S. M., Ralls, P. W., Reynolds, T. B., Stain, S. C. SOUTHEASTERN SURGICAL CONGRESS. 1996: 825–29


    Hepatic adenomas are uncommon hepatic neoplasms that may be identified after life-threatening hemorrhage, or as an incidental radiologic finding. The incidence of malignant transformation is unknown, and the correct treatment strategy is unclear. We examined our 10-year experience in the management of 12 patients with hepatic adenomas. Eleven adults (mean age of 37.6 years) and one 3-month-old were identified. Nine of 10 adult females (90%) were taking a hormonal preparation at the time of diagnosis. Four patients with tumor sizes of 1.0 to 4.0 cm were observed after cessation of oral contraceptives. Four patients with lesions of 5.5 to 13 cm underwent surgical resection. Three had malignant transformation, and two of the three had increased Alpha-fetoprotein levels. Four patients presented with acute hemorrhage and were treated initially by hepatic arterial embolization. We conclude that management of adenomas should be individualized based on their size and mode of presentation. Patients with lesions less than 5 cm and normal alpha-fetoprotein can be safely observed off oral contraceptives and followed by radiologic imaging. Lesions >5 cm should be considered for surgical resection due to the risk of malignancy. Hepatic arterial embolization is a new approach for acute hemorrhage.

    View details for Web of Science ID A1996VJ94300010

    View details for PubMedID 8813164

  • Assessment of resectability of pancreatic head and periampullary tumors by color flow Doppler sonography 67th Annual Session of the Pacific-Coast-Surgical-Association Wren, S. M., Ralls, P. W., Stain, S. C., Kasiraman, A., Carpenter, C. L., Parekh, D. AMER MEDICAL ASSOC. 1996: 812–17


    To examine the sensitivity of color flow Doppler ultrasonography in assessing resectability of pancreatic head and periampullary tumors.Validation cohort study.Tertiary care public hospital.Thirty-seven patients with pancreatic head or periampullary cancer were studied by color flow Doppler examination of the relevant blood vessels.A pancreatic Doppler score (PDS) was defined as the closest circumferential contact of the tumor to the superior mesenteric vein, superior mesenteric artery, or portal vein. A PDS of 1 indicated no contact (n = 9); PDS 2, less than 50% contact (n = 10); PDS 3, 50% to 99% contact (n = 7); and PDS 4, encasement (n = 11). The PDS was compared with operative and histologic resection margins.The lack of vascular invasion was confirmed operatively in 7 of 7 patients with a PDS of 1, and 6 patients who underwent resection had clear histologic margins. Nine (90%) of 10 patients with a PDS of 2 were confirmed to have no vascular invasion, and 3 (43%) of 7 patients who underwent resection had clear margins. Five (83%) of 6 patients with a PDS of 3 had correct operative findings, and both patients who underwent resection had positive margins. Operative confirmation of encasement was found in all 7 patients with a PDS of 4 who had operative exploration, and none underwent resection.Color flow Doppler sonography and PDS predicted resectability and the histologic margin status (positive predictive value, 97%). Patients with a PDS of 1 are predicted to have clear histologic margins after resection. Patients with a PDS of 4 have unresectable tumors, and nonoperative palliation should be considered. Patients with a PDS of 2 or 3 have a high likelihood of positive histologic margins after resection and may be candidates for neoadjuvant chemotherapy.

    View details for Web of Science ID A1996VA59100005

    View details for PubMedID 8712903



    Reconstitution of lethally irradiated mice with a mixture of syngeneic and allogeneic (A+B-->A) bone marrow results in multilineage mixed allogeneic chimerism, donor-specific transplantation tolerance, superior immunocompetence and resistance to graft-vs-host disease. However, the morbidity and mortality associated with lethal irradiation would be a major limitation to the clinical application of chimerism to induce tolerance for solid organ grafts or treat other nonmalignant hematologic diseases. We report here that durable multilineage mixed allogeneic chimerism and donor-specific transplantation tolerance for skin and primarily vascularized allografts can be achieved across multiple histocompatibility barriers using a nonmyeloablative radiation-based approach. The percentage of B10 mouse recipients that engrafted directly correlated with the degree of disparity between donor and recipient and the dose of total body irradiation administered. Although the occurrence of engraftment following conditioning with doses of total body irradiation of > or = 600 cGy was similar for animals receiving bone marrow disparate at MHC or MHC, minor and hematopoietic (Hh-1) loci (67% vs 78%), the level of donor chimerism was significantly less when multiple histocompatibility barriers were present (94.6 +/- 3.8% vs 37.5 +/- 12.5%). Treatment of the recipient with cyclophosphamide 2 days following allogeneic bone marrow transplantation reduced the dose of radiation sufficient for reliable engraftment to only 500 cGy of total body irradiation, regardless of MHC and Hh-1 disparity. Donor chimerism was stable and present in all lineages, with production of lymphoid (T and B cell), NK, and myeloid (erythrocyte, platelet, granulocyte, and macrophage) cells. Mixed chimeras exhibited donor-specific tolerance in vitro, as assessed by mixed lymphocyte culture (MLR) and cytotoxicity (CML) assays, and in vivo to skin and primarily vascularized cardiac allografts. The observation that engraftment and tolerance can be achieved across multiple histocompatibility barriers using nonmyeloablative recipient conditioning may allow allogeneic bone marrow transplantation to be applied to nonmalignant disease states in which lethal conditioning cannot be justified, including the induction of donor-specific tolerance for solid organ transplantation and the treatment of hemoglobinopathies and enzyme deficiency states.

    View details for Web of Science ID A1995TB46800008

    View details for PubMedID 7594573

  • INDIVIDUAL ASSESSMENT OF VISUAL-PERCEPTION BY SURGEONS OBSERVING THE SAME LAPAROSCOPIC ORGANS WITH VARIOUS IMAGING-SYSTEMS Annual Meeting of the Society-of-American-Gastrointestinal-Endoscopic-Surgeons (SAGES) Berci, G., Wren, S. M., Stain, S. C., Peters, J., PAZPARTLOW, M. SPRINGER VERLAG. 1995: 967–73


    Laparoscopic surgery necessitates that operations be performed via a television screen; therefore, image quality is crucial in determining the final outcome. Electronic imaging systems are constantly undergoing revisions and incorporating new ideas. Recently, we have been confronted with a variety of systems, and we, as operators, have no idea what the differences are between the old and the newer systems. As clinicians, we have no electronic yardstick available to compare the options presented or to check the specifications. This study examines critical aspects of image perception. General surgeons, gynecologists, operating-room nurses, as well as allied health personnel all experienced in laparoscopic surgery participated as test subjects. A blinded study was performed in which various camera systems (single chip, three-chip, digitized and nondigitized) were displayed in random fashion. Porcine abdominal areas were displayed using the various imaging units. Participants graded image perception based on the following characteristics: sharpness, color, contrast, and depth of field. The audience were blinded to the types, brand, and number of cameras utilized. A significant preference was shown for digitized systems (P < 0.0001). Also, digitized single-chip cameras scored higher than three-chip cameras (P < 0.05). We propose thorough testing by surgeons and nursing personnel before deciding what type of equipment to purchase.

    View details for Web of Science ID A1995RT66600003

    View details for PubMedID 7482214



    Bone marrow transplantation is an accepted therapy for hematologic malignancies, aplastic anemia, metabolic disorders, and solid tumors. However, graft-versus-host disease (GVHD) and failure of engraftment have limited the widespread application of this technology to nonmalignant disease states. The use of purified bone marrow stem cells has been suggested as an approach to promote engraftment yet avoid GVHD. Although bone marrow stem cells, purified by cell sorting, engraft and repopulate lethally irradiated genetically identical recipients, they do not engraft in major histocompatibility complex (MHC)-disparate allogeneic recipients. We report for the first time the characterization of a novel cell population of donor bone marrow origin, separate from the hematopoietic stem cell, that facilitates engraftment of purified allogeneic bone marrow stem cells in an MHC-specific fashion without causing GVHD. Although 1,000 purified stem cells (c-kit+/Sca-1+/lineage-) reliably repopulate syngeneic mouse recipients, 10 times that number do not engraft in MHC-disparate allogeneic recipients. The addition of as few as 30,000 facilitating cells (CD8+/CD45R+/TCR-) is sufficient to permit engraftment of purified stem cells in MHC-disparate recipients. The cell surface phenotype of this purified cellular population differs significantly from other characterized lineages of lymphoid or myeloid origin. Based on multiparameter rare-events cell sorting, the facilitating fraction is CD8+, CD3+, CD45R+, Thy 1+, class IIdim/intermediate but alpha beta-TCR- and gamma delta-TCR-. This cellular population comprises approximately 0.4% of the total bone marrow and is separate from the hematopoietic stem cell. The coadministration of purified facilitating cells plus stem cells to optimize engraftment yet avoid GVHD may expand the potential application of bone marrow transplantation to disease states in which the morbidity and mortality associated with conventional BMT cannot be justified.

    View details for Web of Science ID A1994PL35900005

    View details for PubMedID 7919363

  • EVIDENCE FOR EARLY TH2 T-CELL PREDOMINANCE IN XENOREACTIVITY TRANSPLANTATION Wren, S. M., Wang, S. C., Thai, N. L., Conrad, B., Hoffman, R. A., Fung, J. J., SIMMONS, R. L., Ildstad, S. T. 1993; 56 (4): 905-911


    Two distinct subsets of CD4+ Th lymphocytes have been characterized by their cytokine profiles: Th 1 (TH1) and Th 2 (TH2). While TH1 cells predominate in cell-mediated responses, TH2 cells support the humoral response. We have examined the mRNA cytokine profile of normal mouse lymphocytes in response to alloantigen versus xenoantigen (rat) in MLC, and present evidence to suggest that early in proliferative responses, alloreactivity is dominated primarily by TH1-type lymphocytes, while xenoreactivity is predominantly TH2. Normal mouse lymphocyte-responding cells were cultured in a one-way MLR with either allo or xeno antigen and examined for production of mRNA for cytokines characteristically produced by TH1 (IL-2, IFN-gamma) or TH2 (IL-4, IL-10) cells. Semiquantitative reverse transcription-polymerase chain reaction analysis was performed for mouse IL-2, IL-4, IL-10, and IFN-gamma mRNA. In the mouse anti-rat xeno response, mRNA for TH2 gene products were upregulated, with greater levels of IL-4 and IL-10 at 24 and 48 hr when compared with controls. In contrast, upregulation of mRNA for TH1 gene products occurred in the mouse anti-mouse allo response, with higher levels of IL-2 and IFN-gamma at 24 and 48 hr. In the anti-xeno response, upregulation of all 4 cytokines occurred by day 4 and peak levels of mRNA for all cytokines examined were 2-3 times that seen for the peak anti-allogeneic response. These data suggest that early xenorecognition may differ from allorecognition by differential activation of the TH2 subset. A better understanding of the balance between Th subset function and cytokine profile in allo and xeno reactivity may allow a more targeted and specific approach to control the early events in xenograft rejection.

    View details for Web of Science ID A1993MD80500025

    View details for PubMedID 8212215



    The generation of nitric oxide (.N = O) during in vitro assays involving lymphocyte-macrophage interaction can result in profound inhibition of lymphocyte proliferation. The present study examined whether .N = O synthesis plays a role in the suppression observed in immune function assays during graft vs host disease (GvHD). By using a parent to F1 model to induce GvHD (C57BL/6J to C57BL/6J x DBA 2J F1), a mild but transient increase in serum NO2- plus NO3- levels was observed on day 12 after inoculation. Resident peritoneal macrophages obtained from mice with GvHD demonstrated enhanced .N = O synthesis in response to LPS, compared with control F1 peritoneal macrophages. Similarly, when splenocytes from GvHD mice were cultured with Con A or LPS enhanced supernatant NO2- levels were observed, compared with control F1 mice. Addition of NG-monomethyl-L-arginine (NMA), a competitive inhibitor of .N = O synthesis, resulted in decreased NO2- levels and greatly enhanced proliferation in response to Con A. Addition of NMA to LPS-stimulated cultures did not enhance proliferation, perhaps as the result of the paucity of B cells in the GvHD population. LPS-induced .N = O synthesis by GvHD splenocytes was blocked by anti-IFN-gamma mAb, whereas Con A-induced .N = O synthesis was relatively unaffected by similar concentrations of anti-IFN-gamma mAb, suggesting different mechanisms of induction of .N = O synthesis. A proliferative response of splenocytes from mice with GvHD to third-party alloantigen was not detectable, even in the presence of NMA. The suppression observed when splenocytes from GvHD animals were added to control TNP-modified self cultures was partially reversed in the presence of NMA. These results demonstrate that .N = O synthesis in both splenocyte and peritoneal macrophage populations from GvHD mice is enhanced, revealing that in vivo priming of macrophages for .N = O synthesis occurs during GvHD. Some, but not all, in vitro tests of immune function by using GvHD splenocytes are suppressed by the generation of .N = O.

    View details for Web of Science ID A1993LP72500037

    View details for PubMedID 8335943



    Reconstitution of mouse recipients with a mixture of syngeneic plus allogeneic bone marrow (A+B-->A) results in stable mixed lymphohematopoietic chimerism and donor-specific transplantation tolerance. Previously, it was reported that administration of large numbers of unmanipulated host-type splenocytes to neonatal or adult radiation bone marrow chimeras resulted in a loss of chimerism and donor-specific transplantation tolerance. To characterize the phenotype(s) of cells that were responsible for this loss of chimerism, we performed depletion of various subsets of unmanipulated B10 splenocytes prior to infusion into mixed allogeneic chimeras (B10 + B10.BR-->B10). Recipients were followed serially to identify changes in the level of donor chimerism and by in vitro functional assays of tolerance. We report here that CD4+ T cells, but not CD8+ T cells, were sufficient to mediate the loss of donor chimerism. In all recipients in which allogeneic chimerism became undetectable, there was a simultaneous loss of donor-specific transplantation tolerance.

    View details for Web of Science ID A1993LK58900033

    View details for PubMedID 8100092



    Reconstitution of B10 recipient mice, conditioned with total body irradiation (950 rads), with 40 x 10(6) untreated F344 or WF rat bone marrow cells results in stable rat stem-cell engraftment with multilineage lymphohematopoietic chimerism. We have now characterized NK cell generation, maturation, and function in fully xenogeneic chimeras (WF rat-->B10 mouse; F344-->B10 mouse). Early during xenogeneic reconstitution, rat-derived NK cells predominated in splenic lymphoid tissue, composing 14-18% of total cells at week 1 and increasing to 35.6-59.9% of total cells at week 2. By week 6, levels of rat NK cells had decreased and stabilized to that expected for normal rat (9-14.2%). The NK chimerism was reliably stable for up to 7 months following reconstitution. Most importantly, rat-derived NK cells were functional in both YAC tumor cytolysis and ADCC assays, suggesting that the xenogeneic mouse host environment was sufficient to support the generation, maturation, and function of rat-derived NK cells.

    View details for Web of Science ID A1993KN01500024

    View details for PubMedID 8434388


    View details for Web of Science ID A1993KN62100177

    View details for PubMedID 8438377


    View details for Web of Science ID A1992KC41300224

    View details for PubMedID 1465976


    View details for Web of Science ID A1992KC41300233

    View details for PubMedID 1465984



    We have applied the model of mixed allogeneic chimerism (A+B-->A), in which stem cells from both allogeneic and syngeneic donor engraft, to determine the in vivo cellular requirements for transfer of tolerance from mixed chimeras to secondary recipients. Using two approaches, we have demonstrated that the persistence of donor-specific transplantation tolerance is dependent on the presence of bone-marrow-derived cells. When untreated bone marrow from mixed chimeras was transferred to irradiated secondary recipient mice, most of the secondary recipients were rescued, but only 48% were demonstrably chimeric. This pattern of repopulation, therefore, allowed us to examine whether chimerism was required to maintain transplantation tolerance. In all of our studies, the presence of allogeneic chimerism was required for successful transfer of tolerance from mixed allogeneic chimeras to irradiated secondary recipients. Only those secondary recipients which repopulated with demonstrable allogeneic chimerism exhibited in vivo and in vitro evidence for transfer of donor-specific transplantation tolerance. These results were confirmed by using transfer of bone marrow from mixed chimeras depleted of allogeneic class I elements. In an attempt to identify a putative population of suppressor cells, second transfer of splenic lymphoid cells from mixed allogeneic chimeras, containing approximately 6 times more T-lymphocytes that were functionally tolerant to donor alloantigens, was also performed with similar results. These data suggest that the in vivo maintenance of tolerance to MHC transplantation alloantigens requires persistence of donor bone marrow-derived alloantigens.

    View details for Web of Science ID A1992KD06200017

    View details for PubMedID 1465769



    The immunological status of Lewis (LEW) recipients of indefinitely surviving (greater than 400 days) orthotopic Brown-Norway (BN) small bowel allografts was investigated 1 to 1 1/2 years after cessation of immunosuppressive therapy with either cyclosporine or FK506 and compared with recipients of syngeneic grafts. A normal proliferative response (as measured by a mixed lymphocyte culture) of recipient peripheral lymph node lymphocytes in response to the donor-specific (BN) and the third-party (ACI) antigen, was observed in all experimental groups. Cytolytic T cell generation (as measured by a standard 51Cr-release cytotoxicity assay) in response to the donor-specific (BN) and the third-party (ACI) antigen was observed also in all groups. A FACS analysis of allograft-recipient splenocytes showed no evidence for systemic lymphoid chimerism. BN or ACI skin grafts transplanted onto recipients of allogeneic and syngeneic small bowel grafts were rejected completely in 12-17 days, while the intestinal grafts remained functional. Immunohistologic evaluation of the allografts, using anti-BN class I and anti-Lewis class II monoclonal antibodies showed anti-BN staining on the epithelial and endothelial structures, whereas the mononuclear cells in the lamina propria stained positively with the anti-LEW monoclonal antibody. However, lymphoid depletion and scarring of Peyer's patches and mesenteric lymph nodes as well as focal obliterative mesenteric arteriopathy, indicative of an indolent chronic rejection, were observed. These data demonstrate that recipients of indefinitely surviving small bowel allografts remain immune competent and do not retain the intestinal graft on the basis of specific hyporesponsiveness to the donor antigens.

    View details for Web of Science ID A1992JP01800022

    View details for PubMedID 1384185


    View details for Web of Science ID A1992HY79500106

    View details for PubMedID 1604698


    View details for Web of Science ID A1992HN85700033

    View details for PubMedID 1566404


    View details for Web of Science ID A1992HN85700034

    View details for PubMedID 1348886



    We report the induction of stable and reliably detectable mixed xenogeneic chimerism through the coadministration of a mixture of untreated rat bone marrow plus T cell-depleted mouse bone marrow into B10 recipients conditioned with total body irradiation (TCD B10 mouse + untreated F344 rat----B10 mouse). Recipients repopulated as true mixed lymphopoietic chimeras, with from 1-21.6% rat-derived lymphoid cells in peripheral blood and splenic lymphoid tissue. Production of rat platelets was also demonstrated. Rat platelet and lymphoid chimerism was reliably detectable in chimeras from 1 to 7 months following reconstitution, suggesting engraftment of the rat bone marrow stem cell. Production of each stem cell-derived lineage appeared to be under independent regulation since a significantly greater proportion of platelets were rat-derived (24-81%) than were lymphocytes (1-21.6% rat), while erythrocytes were preferentially syngeneic (less than 2% rat). The tolerance induced by this model was highly donor strain-specific: donor-specific rat and mouse skin grafts were accepted while MHC-disparate third-party mouse (C3H; H-2k) and rat (Wistar Furth; Rt1Au) skin grafts were promptly rejected. Although specifically prolonged xenogeneic donor rat skin grafts underwent a slow chronic rejection, and some totally disappeared. In spite of this, chimeras retained their lymphoid chimerism, suggesting the presence of skin-specific antigens. This model for mixed xenogeneic chimerism with reliably detectable rat lymphoid cells may provide a model to study the existence of tissue-specific antigens across a species barrier, as well as mechanisms responsible for the induction and maintenance of this strain-specific transplantation tolerance.

    View details for Web of Science ID A1992HP30600022

    View details for PubMedID 1566347



    When untreated F344 rat bone marrow is transplanted into B10 mouse recipients conditioned with total body irradiation, stable fully xenogeneic chimerism (rat----mouse) results. Chimeras are specifically tolerant to the donor strain of rat, survival is excellent (greater than 80% at 8 months), and all stem-cell-derived lineages are produced by the rat stem cell. We have previously demonstrated normal function of T-lymphocytes in these chimeras, but have not examined the immune function of natural killer (NK) cells present. Because NK cells play a critical role in immune surveillance, absence of function could result in a serious immunodeficiency state. We present data here to suggest that rat NK cells that have developed in a mouse stromal environment are normal in function as well as number. In all fully xenogeneic chimeras tested from 8 weeks to 8 months following bone marrow transplantation, NK cells were present at a normal level (10% to 16%). NK cells function in these chimeras, as tested by spontaneous lysis of YAC tumor cell targets, was normal or superior to normal F344 rat and B10 mouse NK cells.

    View details for Web of Science ID A1992HJ05700007

    View details for PubMedID 1501002



    Mixed xenogeneic bone marrow reconstitution (mouse + rat----mouse) results in stable mixed lymphopoietic chimerism (1-48% rat), long-term survival, and the induction of stable functional donor-specific transplantation tolerance to xenoantigens in vivo. To examine the role of negative selection of potentially xenoreactive T lymphocytes during tolerance induction across a species barrier, mixed xenogeneic chimeras (mouse + rat----mouse) were prepared and analyzed using a mixture of mouse and rat bone marrow cells for relative T cell receptor (TCR)-V beta expression on mouse T cells. In mixed xenogeneic chimeras (B10 mouse + rat----B10 mouse), T cell maturation proceeded normally in the presence of rat bone marrow-derived elements, and functional donor-specific tolerance to rat xenoantigens was present when assessed by mixed lymphocyte reactivity in vitro. V beta 5, which is expressed at high (undeleted) levels in normal B10 mice, was consistently deleted in B10 recipients of Wistar Furth (WF), but not F344 rat bone marrow, whereas the coadministration of either F344 rat or WF rat bone marrow with B10 mouse bone marrow cells resulted in a significant decrease in expression of TCR-V beta 11. Taken together, these data demonstrate for the first time that rat bone marrow-derived cells can contribute in a strain-specific manner to the ligand for negative selection of specific mouse TCR-V beta during tolerance induction across a species barrier.

    View details for Web of Science ID A1992GY43600018

    View details for PubMedID 1530958



    We have developed a model to study cross-species bone marrow transplantation and the associated donor-specific transplantation tolerance induced using fully xenogeneic chimeras. Reconstitution of lethally irradiated B10 mice with untreated F344 rat bone marrow cells results in fully xenogeneic chimerism (F344 rat----B10 mouse). Survival of recipients is excellent (greater than 80% at 100 days) and stable rat lymphoid and multilineage chimerism are present throughout the life of the chimeras. Recipients are specifically tolerant to donor-type skin xenografts yet are competent to reject major histocompatibility complex (MHC)--disparate third party strain rat xenografts. Although prolonged, donor-specific skin xenografts underwent chronic rejection which had its onset at approximately 40 days following skin graft placement. We have now examined these chimeras by serial flow cytometry typing to determine whether this is due to skin-specific antigens expressed on skin, but not on the bone marrow elements to which the chimeras were rendered tolerant. In all animals examined, lymphopoietic chimerism persisted unchanged even after the onset of inflammation in the grafts, suggesting the presence of skin specific antigens. This model may provide a method to study tissue and organ specific antigens recognized across a species barrier.

    View details for Web of Science ID A1991GK45000003

    View details for PubMedID 1758170



    We recently reported the model of fully xenogeneic chimerism achieved by transplantation of rat bone marrow into mouse recipients (F344 rat----B10 mouse), resulting in stable long-term rat lymphoid chimerism. We have now extended this model to examine whether developing precursor rat T cells from rat bone marrow stem cells can undergo normal differentiation in mature lymphocytes under the influence of a xenogeneic mouse thymus. We examined thymic and splenic lymphoid cells from fully xenogeneic chimeras starting 1 week after bone marrow transplantation to characterize early T-cell repopulation and phenotype. Our data suggest that developing rat precursor T cells are able to undergo normal differentiation in the mouse thymus. The first precursor T cells appeared 2 weeks after reconstitution and by week 10 accounted for more than 90% of thymocytes present in the chimeras. In chimeras, developing rat T lymphocytes in the mouse thymus exhibited an immature pattern (Thy 1.1+, alpha beta-TCRdull, CD4+ plus CD8+) when analyzed by flow cytometry. This pattern was similar to a normal rat. In contrast, splenic T-lymphoid cells showed a mature rat phenotype (Thy 1.1-, alpha beta-TCRhi, CD4+ or CD8+), again similar to a normal rat. This development began 2 weeks after bone marrow transplantation, and both thymus and spleen from chimeras exhibited "normal" rat T-cell staining profiles by 10 weeks after reconstitution. Overall, these data indicate that developing rat T cells are capable of undergoing normal maturation in a xenogeneic mouse thymus of tolerant animals.

    View details for Web of Science ID A1991FZ62800016

    View details for PubMedID 1858033



    Transplantation of untreated F344 rat bone marrow into irradiated B10 mouse recipients (non-TCD F344----B10) to produce fully xenogeneic chimeras resulted in stable xenogeneic lymphoid chimerism, ranging from 82% to 97% rat. Survival of animals was excellent, without evidence for GVH disease. The specificity of tolerance which resulted was highly donor-specific; MHC disparate third party mouse and rat skin grafts were promptly rejected while donor-specific F344 grafts were significantly prolonged (MST greater than 130 days). Multi-lineage rat stem cell-derived progeny including lymphoid cells (T- and B-lymphocytes), myeloid cells, erythrocytes, platelets, and natural killer (NK) cells were present in the fully xenogenic chimeras up to 7 months after bone marrow transplantation. Immature rat T-lymphocytes matured and acquired the alpha/beta T-cell receptor in the thymus of chimeras in a pattern similar to normal rat controls, suggesting that immature T-lymphocytes of rat origin could interact with the murine xenogeneic thymic stroma to undergo normal maturation and differentiation. This model may be useful to study the mechanisms responsible for the induction and maintenance of donor-specific transplantation tolerance across a species barrier.

    View details for Web of Science ID A1991FY50200018

    View details for PubMedID 1856629



    Mixed allogeneic reconstitution, in which a mixture of T-cell-depleted bone marrow of syngeneic host and allogeneic donor type is transplanted into a lethally irradiated recipient (A+B----A), results in mixed lymphopoietic chimerism with engraftment of a mixture of both host and donor bone marrow elements. Recipients are specifically tolerant to donor both in vitro and in vivo. Donor-specific skin grafts survive indefinitely when they are placed after full bone marrow repopulation at 28 days, while third-party grafts are rapidly rejected. To determine whether a delay of a month or more for full bone marrow repopulation is required before a donor-specific graft can be placed, we have now examined whether tolerance induction can be achieved if a graft is placed at the time of bone marrow transplantation. Permanent acceptance of donor-specific B10.BR skin grafts occurred when mixed allogeneic chimerism (B10+B10.BR----B10) was induced and a simultaneous allogeneic donor graft placed. In vitro, mixed reconstituted recipients were specifically tolerant to the B10.BR donor lymphoid cells but fully reactive to MHC-disparate third-party (BALB/c; H-2dd) when assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. These data therefore indicate that a donor-specific graft placed at the time of mixed allogeneic reconstitution is permanently accepted without rejection. To determine whether an allogeneic skin graft alone without allogeneic bone marrow would be sufficient to induce tolerance, syngeneic reconstitution (B10----B10) was carried out, and a simultaneous B10.BR allogeneic skin graft placed. Although skin grafts were prolonged in all recipients, all grafts rejected when full lymphopoietic repopulation occurred at 28 days. Taken together, these data suggest that allogeneic donor bone marrow elements are required for the induction and maintenance of donor-specific transplantation tolerance and that allogeneic skin grafts alone are not sufficient for tolerance induction.

    View details for Web of Science ID A1991FR73600022

    View details for PubMedID 1828637



    Chimerism, or the coexistence of tissue elements from more than one genetically different strain or species in an organism, is the only experimental state that results in the induction of donor-specific transplantation tolerance. Transplantation of a mixture of T-cell-depleted syngeneic (host-type) plus T-cell-depleted allogeneic (donor) bone marrow into a normal adult recipient mouse (A + B----A) results in mixed allogeneic chimerism. Recipient mice exhibit donor-specific transplantation tolerance, yet have full immunocompetence to recognize and respond to third-party transplantation antigens. After complete hematolymphopoietic repopulation at 28 days, animals accept a donor-specific skin graft but reject major histocompatibility complex (MHC) locus-disparate third-party grafts. We now report that permanent graft acceptance can also be achieved when the graft is placed at the time of bone marrow transplantation. Histologically, grafts were viable and had only minimal inflammatory changes. This model may have potential future clinical application for the induction of donor-specific transplantation tolerance.

    View details for Web of Science ID A1991FF05500014

    View details for PubMedID 2056405


    View details for Web of Science ID A1991EV39000289

    View details for PubMedID 1990670


    View details for Web of Science ID A1991EV39000322

    View details for PubMedID 1671307



    We have recently reported the induction of long-term specific hyporeactivity to transplantation across a species barrier (rat----mouse) through reconstitution of irradiated recipients with a mixture of T-cell-depleted host-type C57BL/10Sn (B10) bone marrow plus T-cell-depleted F344 rat bone marrow (B10+F344----B10) (1). We report here the influence of selective T cell depletions of host-type and/or donor-type bone marrow on induction of such hyporeactivity. Mice that received mixed bone marrow inocula in which the syngeneic marrow had been T-cell-depleted, whether or not the xenogeneic donor marrow had been treated, showed specific prolongation of F344 donor-type skin grafts. In contrast, F344 rat skin grafts were promptly rejected by animals that had received mixed bone marrow inocula in which the syngeneic component had not been T-cell-depleted. Serologic reactivity against F344 lymphocyte cell surface antigens also differed among the four groups; animals that had received untreated syngeneic bone marrow demonstrated high levels of reactivity to F344 target cells, while animals reconstituted with mixed inocula in which the syngeneic component had been T-cell-depleted exhibited low levels, if any, of serologic reactivity against F344 splenocytes. This model for mixed xenogeneic reconstitution may be helpful to define the conditions required for induction of transplantation tolerance across a species barrier.

    View details for Web of Science ID A1986A511800017

    View details for PubMedID 3513395



    Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts, whether or not the allogeneic bone marrow was T cell depleted. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. In addition, experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it. This system may be helpful as a model for the study of alloresistance and for the identification of syngeneic cell phenotypes, which when present prevent engraftment of allogeneic marrow.

    View details for Web of Science ID A1986AWM4600006

    View details for PubMedID 2933464



    Mixed allogeneically reconstituted mice (B10 + B10.D2----B10) that specifically accept B10.D2 tail skin allografts were examined for in vivo and in vitro immunocompetence, patterns of hematopoietic repopulation, and in vitro reactivity. In vitro, mixed allogeneic chimeras (B10 + B10.D2----B10) manifested specific tolerance in mixed lymphocyte reactions and cell-mediated lympholysis to B10 and B10.D2 splenocytes, with normal responses to third-party (B10.BR) cells. Such chimeras were immunocompetent in B cell and helper T cell responses, as assessed by their primary plaque forming cell responses to in vivo sheep red blood cell immunization. This is in contrast to fully allogeneic chimeras, which responded less well. In addition, survival of the mixed allogeneic chimeras in a conventional animal facility was superior to that of fully allogeneic chimeras, and similar to syngeneically reconstituted (B10----B10) mice. Specific tolerance to skin grafts, degree of allogeneic engraftment, and persistence of chimerism was also assessed in a noncongenic mixed allogeneic combination (B10 + C3H----B10). Such animals manifested specific hyporeactivity to C3H skin allografts, but eventual chronic rejection of the grafts occurred in spite of stable and persistent mixed chimerism. MHC-congenic (B10.BR) skin grafts were accepted indefinitely in the same animals, suggesting that skin-specific non-major histocompatibility complex antigens were responsible for rejection of the C3H skin allografts.

    View details for Web of Science ID A1985ALW4900017

    View details for PubMedID 3159825



    Mixed xenogeneically reconstituted mice (F344 rat + C57BL/10Sn----C57BL/10Sn), which specifically retain F344 tail skin xenografts, were studied for the specificity of such hyporeactivity and for in vitro reactivity and immunocompetence. Survival of mixed reconstituted animals was excellent, without evidence for graft vs. host disease. Donor-type tail skin grafts were specifically prolonged (mean survival time = 80 d) in comparison with normal controls and syngeneically reconstituted animals. In vitro, such animals manifested specific hyporeactivity by mixed lymphocyte reaction and cell-mediated lympholysis to F344 rat and B10 cells, with normal response to third-party rat (Wistar-Furth) and mouse (B10.BR). Examination of lymphoid tissues with a fluorescence-activated cell sorter revealed low levels, if any, of donor-type cells detectable. This system offers a model for investigation of xenogeneic transplantation tolerance.

    View details for Web of Science ID A1984TX70100015

    View details for PubMedID 6239902



    Immunization of C57BL/6 mice with BCGcw stimulated a population of "suppressor cells" which had a decreased capacity to induce the graft-versus-host response. The graft-versus-host response was quantitated using the Simonsen splenomegaly assay. F1 mice (C57BL/6 X CBA) were inoculated intraperitoneally with 1 X 10(8) parental (C57BL/6) or (CBA) spleen cells. The F1 mice were sacrificed 13 days later and the resulting splenomegaly was 3-4 times the normal amount. F1 mice which were injected with parental BCGcw-primed C57BL/6 spleen cells had a 50% inhibition of splenomegaly, whereas BCGcw-primed CBA spleen cells (a strain which does not develop suppressor cells) did not show this inhibition. In vitro results also confirmed that only C57BL/6 mice and not CBA mice developed suppressor cells after BCGcw immunization. A second study showed that X-irradiated (1000 R) BCGcw-primed "suppressor cells" could inhibit splenomegaly caused by the inoculation of normal parental C57BL/6 cells into F1 mice. The mechanism by which BCGcw-primed "suppressor cells" caused this inhibition of splenomegaly was delineated and found to be dependent upon the secretion of prostaglandin (PGE-1). Indomethacin and aspirin, potent inhibitors of prostaglandin synthesis, blocked the activity of C57BL/6 BCGcw "suppressor cells" and splenomegaly resulted. Systemic administration of the prostaglandin (15S)-15-methyl PGE-1 reduced splenomegaly approximately 50% in F1 mice which were injected with C57BL/6 or CBA cells. These results indicated that immunization with BCGcw stimulated a population of "suppressor cells" which could cause a decrease in graft-versus-host response and that the secretion of prostaglandin was responsible for this inhibition.

    View details for Web of Science ID A1983QM43500016

    View details for PubMedID 6220811