Honors & Awards


  • Arnold P. Gold Foundation Award for Humanism and Excellence in Teaching, Stanford University (2023)
  • Resident Research Award Finalist, Pacific Coast Surgical Association (2020)
  • Resident Research Award, American College of Surgeons (ACS) (2018-2020)
  • Transplant and Tissue Engineering Research Grant, Stanford University (2018-2020)
  • Consult Resident Of The Year Award, Stanford Surgery (2018)
  • Stanford University Li Ka Shing Travel Grant, Stanford University (2018)
  • Best Clinical Oral Presentation at Stanford University Holman Research Conference, Stanford University (2017)
  • Stanford University Undergraduate Minor Grant, Stanford University (2011)
  • Stanford University Mechanical Engineering Summer Research Internship Grant, Stanford University (2010)
  • Stanford University Undergraduate Minor Grant, Stanford University (2009)
  • NASA Research Grant Recipient, NASA (2008)

Professional Education


  • MD, Icahn School of Medicine At Mount Sinai (2016)
  • BA Honors, Stanford University, Philosophy and Honors in Ethics in Society (2012)

All Publications


  • Housing Status Changes Are Associated With Cancer Outcomes Among US Veterans. Health affairs (Project Hope) Decker, H. C., Graham, L. A., Titan, A., Hawn, M. T., Kanzaria, H. K., Wick, E., Kushel, M. B. 2024; 43 (2): 234-241

    Abstract

    Cancer is a leading cause of death in older unhoused adults. We assessed whether being unhoused, gaining housing, or losing housing in the year after cancer diagnosis is associated with poorer survival compared with being continuously housed. We examined all-cause survival in more than 100,000 veterans diagnosed with lung, colorectal, and breast cancer during the period 2011-20. Five percent were unhoused at the time of diagnosis, of whom 21 percent gained housing over the next year; 1 percent of veterans housed at the time of diagnosis lost housing. Continuously unhoused veterans and veterans who lost their housing had poorer survival after lung and colorectal cancer diagnosis compared with those who were continuously housed. There was no survival difference between veterans who gained housing after diagnosis and veterans who were continuously housed. These findings support policies to prevent and end homelessness in people after cancer diagnosis, to improve health outcomes.

    View details for DOI 10.1377/hlthaff.2023.01003

    View details for PubMedID 38315919

  • Housing Status, Cancer Care, and Associated Outcomes Among US Veterans. JAMA network open Decker, H. C., Graham, L. A., Titan, A., Kanzaria, H. K., Hawn, M. T., Kushel, M., Wick, E. 2023; 6 (12): e2349143

    Abstract

    Cancer is a leading cause of death among older people experiencing homelessness. However, the association of housing status with cancer outcomes is not well described.To characterize the diagnosis, treatment, surgical outcomes, and mortality by housing status of patients who receive care from the US Department of Veterans Affairs (VA) health system for colorectal, breast, or lung cancer.This retrospective cohort study identified all US veterans diagnosed with lung, colorectal, or breast cancer who received VA care between October 1, 2011, and September 30, 2020. Data analysis was performed from February 13 to May 9, 2023.Veterans were classified as experiencing homelessness if they had any indicators of homelessness in outpatient visits, clinic reminders, diagnosis codes, or the Homeless Operations Management Evaluation System in the 12 months preceding diagnosis, with no subsequent evidence of stable housing.The major outcomes, by cancer type, were as follows: (1) treatment course (eg, stage at diagnosis, time to treatment initiation), (2) surgical outcomes (eg, length of stay, major complications), (3) overall survival by cancer type, and (4) hazard ratios for overall survival in a model adjusted for age at diagnosis, sex, stage at diagnosis, race, ethnicity, marital status, facility location, and comorbidities.This study included 109 485 veterans, with a mean (SD) age of 68.5 (9.7) years. Men comprised 92% of the cohort. In terms of race and ethnicity, 18% of veterans were Black, 4% were Hispanic, and 79% were White. A total of 68% of participants had lung cancer, 26% had colorectal cancer, and 6% had breast cancer. There were 5356 veterans (5%) experiencing homelessness, and these individuals more commonly presented with stage IV colorectal cancer than veterans with housing (22% vs 19%; P = .02). Patients experiencing homelessness had longer postoperative lengths of stay for all cancer types, but no differences in other treatment or surgical outcomes were observed. These patients also demonstrated higher rates of all-cause mortality 3 months after diagnosis for lung and colorectal cancers, with adjusted hazard ratios of 1.1 (95% CI, 1.1-1.2) and 1.3 (95% CI, 1.2-1.4) (both P < .001), respectively.In this large retrospective study of US veterans with cancer, homelessness was associated with later stages at diagnosis for colorectal cancer. Differences in lung and colorectal cancer survival between patients with housing and those experiencing homelessness were present but smaller than observed in other settings. These findings suggest that there may be important systems in the VA that could inform policy to improve oncologic outcomes for patients experiencing homelessness.

    View details for DOI 10.1001/jamanetworkopen.2023.49143

    View details for PubMedID 38127343

  • Radiation-Induced Morphea of the Breast Treated With Wide Local Excision and Abdominal Free Flap Breast Reconstruction. Eplasty Titan, A., Mohan, A. T., Tokuyama, M., Mirbegian, J., Bean, G. R., Lee, G. K. 2023; 23: e50

    Abstract

    Radiation-induced morphea (RIM) associated with breast cancer treatment is a rare and underdiagnosed skin complication of radiotherapy that can lead to severe and painful contractures, resulting in disfigurement, failure of reconstruction, and poor quality of life in patients. The condition may present on a spectrum of local or more generalized forms involving skin over the breast and anterior chest wall. This diagnosis must be differentiated from post-radiation fibrosis, infection, cancer recurrence, inflammatory breast cancer, and other inflammatory conditions as the clinical course and treatment approaches differ. Various noninvasive and topical agents have been used; however, many cases are refractory to treatment. Surgery has been less commonly described in the management of generalized RIM. This report describes a case of RIM in a patient with breast cancer who experienced simultaneous resolution of symptoms as well as successful breast reconstruction using autologous free-tissue transfer.

    View details for DOI 10.1097/01.SMJ.0000140866.97278.87

    View details for PubMedID 37664810

    View details for PubMedCentralID PMC10472431

  • Reduction of Tendon Fibrosis Using Galectin-3 Inhibitors. Plastic and reconstructive surgery Spielman, A. F., Griffin, M. F., Titan, A. L., Guardino, N., Cotterell, A. C., Akras, D., Wan, D. C., Longaker, M. T. 2023

    Abstract

    BACKGROUND: Fibrosis is a complication of both tendon injuries and repairs. We aim to develop a mouse model to assess tendon fibrosis and to identify an antifibrotic agent capable of overcoming tendon fibrosis.METHODS: Adult C57Bl/6 mice underwent a skin incision to expose the Achilles tendon, followed by 50% tendon injury and abrasion with sandpaper. Sham surgeries were conducted on contralateral hindlimbs. Histology and immunofluorescent staining for fibrotic markers (Col1, alpha-SMA) were used to confirm that the model induced tendon fibrosis. A second experiment was conducted to further examine the role of alpha-SMA in adhesion formation using alpha-SMA.mTmG mice (6-8 weeks old) (n=3) with the same injury model. The control group (tendon injury) was compared to the sham group, using the contralateral limb with skin incision only. A second experiment was conducted to further examine the role of alpha-SMA in adhesion formation using alpha-SMA.mTmG mice (6-8 weeks old) (n=3) with the same injury model. The control group (tendon injury) was compared to the sham group, using the contralateral limb with skin incision only. Lastly, alpha-SMA.mTmG mice were randomized to either condition 1. Tendon injury (control group) or 2. Tendon injury with Galectin-3 inhibitor (Gal3i) treatment at time of injury (treatment group).RESULTS: Histological analyses confirmed tendon thickening and collagen deposition after tendon injury and abrasion compared to control. Immunofluorescence showed higher levels of Col1 and alpha-SMA protein expression after injury compared to sham (*p<0.05). RT-qPCR also demonstrated increased gene expression of Col1 and alpha-SMA after injury compared to sham (*p<0.05). Gal3 protein expression also increased after injury and co-localized with alpha-SMA positive fibroblasts surrounding the fibrotic tendon. Gal3i treatment decreased collagen deposition and scarring observed in the treatment group (*p<0.05). Flow cytometry analysis further showed reduced numbers of profibrotic fibroblasts (CD26+) in the treatment compared to the control group (*p<0.05).CONCLUSIONS: Our study provides a reproducible and reliable model to investigate tendon fibrosis. Findings suggest the potential of Gal3i to overcome fibrosis resulting from tendon injuries.

    View details for DOI 10.1097/PRS.0000000000010880

    View details for PubMedID 37344932

  • State of the art review: The management of chronic vascular disorders in the hand and upper limb. The Journal of hand surgery, European volume Titan, A. L., Chang, J., Megerle, K., Murray, P., Hammert, W. 2023: 17531934221145498

    Abstract

    This review article summarizes the basic principles of vascular anatomy, physiology, diagnostic work-up and treatment for patients with nontraumatic upper extremity vascular disorders. Vascular disorders can be considered vasospastic or occlusive. The most commonly encountered vasospastic condition is Raynaud's Phenomenon secondary to scleroderma. While historically this has been managed medically with vasodilators, more advanced cases can benefit from surgical treatment to improve blood flow and minimize tissue loss, with compelling evidence that earlier surgical intervention can modify disease process and should be considered. Occlusive disease can present as aneurysm or thrombosis and often requires surgical treatment with resection of the occluded segment with or without vascular reconstruction. In advanced atherosclerotic disease or end stage ischemia, arterialization of the venous system can be considered to avoid more proximal amputations.

    View details for DOI 10.1177/17531934221145498

    View details for PubMedID 36753288

  • Does delaying surgery following induction chemotherapy compromise survival in patients with mesothelioma? JOURNAL OF CANCER METASTASIS AND TREATMENT Wong, L., Baiu, I., Leipzig, M., Titan, A., Liou, D. Z., Lui, N., Berry, M., Shrager, J. B., Backhus, L. 2023; 9
  • Multiomic analysis reveals conservation of cancer-associated fibroblast phenotypes across species and tissue of origin. Cancer cell Foster, D. S., Januszyk, M., Delitto, D., Yost, K. E., Griffin, M., Guo, J., Guardino, N., Delitto, A. E., Chinta, M., Burcham, A. R., Nguyen, A. T., Bauer-Rowe, K. E., Titan, A. L., Salhotra, A., Jones, R. E., da Silva, O., Lindsay, H. G., Berry, C. E., Chen, K., Henn, D., Mascharak, S., Talbott, H. E., Kim, A., Nosrati, F., Sivaraj, D., Ransom, R. C., Matthews, M., Khan, A., Wagh, D., Coller, J., Gurtner, G. C., Wan, D. C., Wapnir, I. L., Chang, H. Y., Norton, J. A., Longaker, M. T. 2022

    Abstract

    Cancer-associated fibroblasts (CAFs) are integral to the solid tumor microenvironment. CAFs were once thought to be a relatively uniform population of matrix-producing cells, but single-cell RNA sequencing has revealed diverse CAF phenotypes. Here, we further probed CAF heterogeneity with a comprehensive multiomics approach. Using paired, same-cell chromatin accessibility and transcriptome analysis, we provided an integrated analysis of CAF subpopulations over a complex spatial transcriptomic and proteomic landscape to identify three superclusters: steady state-like (SSL), mechanoresponsive (MR), and immunomodulatory (IM) CAFs. These superclusters are recapitulated across multiple tissue types and species. Selective disruption of underlying mechanical force or immune checkpoint inhibition therapy results in shifts in CAF subpopulation distributions and affected tumor growth. As such, the balance among CAF superclusters may have considerable translational implications. Collectively, this research expands our understanding of CAF biology, identifying regulatory pathways in CAF differentiation and elucidating therapeutic targets in a species- and tumor-agnostic manner.

    View details for DOI 10.1016/j.ccell.2022.09.015

    View details for PubMedID 36270275

  • Eligibility for Lung Cancer Screening Among Women Receiving Screening for Breast Cancer. JAMA network open Titan, A. L., Baiu, I., Liou, D., Lui, N. S., Berry, M., Shrager, J., Backhus, L. 2022; 5 (9): e2233840

    View details for DOI 10.1001/jamanetworkopen.2022.33840

    View details for PubMedID 36178692

  • Management of an internal hernia through the foramen of Winslow. Trauma surgery & acute care open Titan, A. L., Garagliano, J. M., Spain, D. 2022; 7 (1): e000960

    View details for DOI 10.1136/tsaco-2022-000960

    View details for PubMedID 35813558

    View details for PubMedCentralID PMC9214427

  • Management of an internal hernia through the foramen of Winslow TRAUMA SURGERY & ACUTE CARE OPEN Titan, A., Garagliano, J. M., Spain, D. 2022; 7 (1)
  • Partial Tendon Injury at the Tendon-to-Bone Enthesis Activates Skeletal Stem Cells. Stem cells translational medicine Titan, A. L., Davitt, M., Foster, D., Salhotra, A., Menon, S., Chen, K., Fahy, E., Lopez, M., Jones, R. E., Baiu, I., Burcham, A., Januszyk, M., Gurtner, G., Fox, P., Chan, C., Quarto, N., Longaker, M. 2022

    Abstract

    The tendon enthesis plays a critical role in facilitating movement and reducing stress within joints. Partial enthesis injuries heal in a mechanically inferior manner and never achieve healthy tissue function. The cells responsible for tendon-to-bone healing remain incompletely characterized and their origin is unknown. Here, we evaluated the putative role of mouse skeletal stem cells (mSSCs) in the enthesis after partial-injury. We found that mSSCs were present at elevated levels within the enthesis following injury and that these cells downregulated TGFβ signaling pathway elements at both the RNA and protein levels. Exogenous application of TGFβ post-injury led to a reduced mSSC response and impaired healing, whereas treatment with a TGFβ inhibitor (SB43154) resulted in a more robust mSSC response. Collectively, these data suggest that mSSCs may augment tendon-to-bone healing by dampening the effects of TGFβ signaling within the mSSC niche.

    View details for DOI 10.1093/stcltm/szac027

    View details for PubMedID 35640155

  • Cancer-Associated Fibroblasts Share Highly Conserved Phenotypes and Functions Across Tumor Types and Species Foster, D. S., Januszyk, M., Yost, K. E., Chinta, M., Titan, A. L., Wapnir, I. L., Gurtner, G. C., Chang, H. Y., Norton, J. A., Longaker, M. T. ELSEVIER SCIENCE INC. 2021: S243-S244
  • Integrated spatial multiomics reveals fibroblast fate during tissue repair. Proceedings of the National Academy of Sciences of the United States of America Foster, D. S., Januszyk, M., Yost, K. E., Chinta, M. S., Gulati, G. S., Nguyen, A. T., Burcham, A. R., Salhotra, A., Ransom, R. C., Henn, D., Chen, K., Mascharak, S., Tolentino, K., Titan, A. L., Jones, R. E., da Silva, O., Leavitt, W. T., Marshall, C. D., des Jardins-Park, H. E., Hu, M. S., Wan, D. C., Wernig, G., Wagh, D., Coller, J., Norton, J. A., Gurtner, G. C., Newman, A. M., Chang, H. Y., Longaker, M. T. 2021; 118 (41)

    Abstract

    In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive, in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to skin injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to reveal potential mechanisms controlling fibroblast fate during migration, proliferation, and differentiation following skin injury, and thereby reexamine the canonical phases of wound healing. These findings have broad implications for the study of tissue repair in complex organ systems.

    View details for DOI 10.1073/pnas.2110025118

    View details for PubMedID 34620713

  • Skin angiography assisted mastectomy in secondary breast angiosarcoma: Complete clinical response after neoadjuvant immunotherapy. The breast journal Ju, T., Foster, D., Titan, A., Najjar, S., Bean, G. R., Ganjoo, K., Wapnir, I. 2021

    Abstract

    Radiation-induced breast angiosarcoma, or secondary angiosarcoma (SAS), is a rare entity with a high risk of metastatic recurrence. Herein, we describe the use of intraoperative fluorescence-based skin angiography to guide surgical resection following a novel immunotherapy-based regimen for SAS resulting in a complete pathological response.

    View details for DOI 10.1111/tbj.14270

    View details for PubMedID 34173294

  • The role of gender in non-small cell lung cancer: a narrative review JOURNAL OF THORACIC DISEASE Baiu, I., Titan, A. L., Martin, L. W., Wolf, A., Backhus, L. 2021; 13 (6): 3816-3826
  • The role of gender in non-small cell lung cancer: a narrative review. Journal of thoracic disease Baiu, I., Titan, A. L., Martin, L. W., Wolf, A., Backhus, L. 2021; 13 (6): 3816-3826

    Abstract

    The role of gender in the development, treatment and prognosis of thoracic malignancies has been underappreciated and understudied. While most research has been grounded in tobacco-related malignancies, the incidence of non-smoking related lung cancer is on the rise and disproportionately affecting women. Recent research studies have unveiled critical differences between men and women with regard to risk factors, timeliness of diagnosis, incongruent screening practices, molecular and genetic mechanisms, as well as response to treatment and survival. These studies also highlight the increasingly recognized need for targeted therapies that account for variations in the response and complications as a function of gender. Similarly, screening recommendations continue to evolve as the role of gender is starting to be ellucidated. As women have been underrepresented in clinical trials until recently, the data regarding optimal care and outcomes is still lagging behind. Understanding the underlying similarities and differences between men and women is paramount to providing adequate care and prognostication to patients of either gender. This review provides an overview of the critical role that gender plays in the care of patients with non-small cell lung cancer and other thoracic malignancies, with an emphasis on the need for increased awareness and further research to continue elucidating these disparities.

    View details for DOI 10.21037/jtd-20-3128

    View details for PubMedID 34277072

    View details for PubMedCentralID PMC8264700

  • Navigating the Infinite Number of Educational Resources: The Development of a Publicly Available Surgical Educational Digital Resource Library. Journal of surgical education Titan, A. L., Jadi, J., Prigoff, J. G., Lewis, J. D., Adams, S., Brownstein, M. 2021

    Abstract

    OBJECTIVE: There has been an explosion of digital resources available for general surgical education and board preparation. This makes it difficult for a new learner, regardless of their training level, to determine which resources best fit their needs. The uncertainty surrounding resource selection due to the large number of options causes stress, anxiety, and inefficiency for surgical learners. Our objective was to develop a digital surgical educational resource library to assist with selection.DESIGN: A needs assessment via multi-center focus groups encompassing all levels of learners from various subspecialties and training levels (medical students, trainees, junior surgeons, and senior surgeons) was performed to determine what information is desired in a surgical resource library. We conducted follow-up interviews and surveys to learn which resources were most commonly used for studying throughout training.SETTING: Multi-institutional RESULTS: The initial needs assessment detailed requests for an expansive array of surgical resources characterized by media type and price. We identified 104 resources that met these criteria. There were 33 resources used by medical students, 37 by residents, 16 used specifically for surgical boards preparation, and 25 by attending surgeons. These resources were composed of textbooks, review books, question banks, audio resources, video resources, and review courses. The prices of the resources ranged from free to greater than 400 dollars.CONCLUSIONS: A digital resource library should be broad and must address needs that change along a learner's career. Changes and improvements are required not only to meet the changing needs of the learners, but also to ensure the library remains current with the ever-growing number of resources. We plan to incorporate reviews of the resources from those surveyed to help visitors of the online library determine which resources may best suit their needs. Development of a digital resource library may assist learners by helping them easily identify what is available and has been peer reviewed allowing them to determine what best meets their educational needs.

    View details for DOI 10.1016/j.jsurg.2021.04.019

    View details for PubMedID 34049824

  • Impact of policy-based and institutional interventions on postoperative opioid prescribing practices. American journal of surgery Titan, A., Doyle, A., Pfaff, K., Baiu, I., Lee, A., Graham, L., Shelton, A., Hawn, M. 2021

    Abstract

    BACKGROUND: We assessed the impact of policy-based and institutional interventions to limit postoperative opioid prescribing.METHODS: Retrospective cohort study of patients who underwent laparoscopic/open appendectomies, laparoscopic/open cholecystectomies, and laparoscopic/open inguinal hernia repair during a 6-month interval in 2018 (control), 2019 (post-policy intervention), and 2020 (post-institutional intervention) to assess changes in postoperative opioid prescribing patterns. A survey was collected for the 2020 cohort.RESULTS: Comparing the 762 patients identified in 2018, 2019, and 2020 cohorts there was a significant decrease in mean opioid tabs prescribed (23.5±8.9 vs. 16.2±7.0 vs. 12.8±4.9, p<0.01) and mean OME dosage (148.0±68.0 vs. 108.6±51.8 vs. 95.4±38.0, p<0.01), without a difference in refill requests. Patient survey (response rate 63%) indicated 91.4% of patients reported sufficient pain control.CONCLUSION: Formalized opioid-prescribing guidelines and statewide regulations can significantly decrease postoperative opioid prescribing with good patient satisfaction. Surgeon education may facilitate efforts to minimize narcotic over-prescription without compromising pain management.

    View details for DOI 10.1016/j.amjsurg.2021.02.004

    View details for PubMedID 33593614

  • Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries LANCET Knight, S. R., Shaw, C. A., Pius, R., Drake, T. M., Norman, L., Ademuyiwa, A. O., Adisa, A. O., Aguilera-Arevalo, M., Al-Saqqa, S. W., Al-Slaibi, I. S., Bhangu, A., Biccard, B. M., Brocklehurst, P., Costas-Chavarri, A., Chu, K. M., Dare, A. J., Elhadi, M., Fairfield, C. J., Fitzgerald, J., Ghosh, D. N., Glasbey, J., Henegouwen, M., Ingabire, J., Kingham, T., Lapitan, M. M., Lawani, I., Lieske, B., Lilford, R. J., Martin, J., Mclean, K. A., Moore, R. L., Morton, D., Nepogodiev, D., Ntirenganya, F., Pata, F., Pinkney, T. D., Qureshi, A. U., Ramos-De la Medina, A., Riad, A. M., Salem, H., Simoes, J., Spence, R. T., Smart, N. J., Tabiri, S., Thomas, H. S., Weiser, T. G., West, M. A., Whitaker, J., Harrison, E. M., GlobalSurg Collaborative, Global Surg Writing Grp 2021; 397 (10272): 387–97

    Abstract

    80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality.This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494.Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70-8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39-8·80) and upper-middle-income countries (2·06, 1·11-3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26-11·59) and upper-middle-income countries (3·89, 2·08-7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications.Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications.National Institute for Health Research Global Health Research Unit.

    View details for DOI 10.1016/S0140-6736(21)00001-5

    View details for Web of Science ID 000614227700026

    View details for PubMedID 33485461

    View details for PubMedCentralID PMC7846817

  • Proceed with Caution: Mouse Deep Digit Flexor Tendon Injury Model. Plastic and reconstructive surgery. Global open Titan, A. L., Fahy, E. n., Chen, K. n., Foster, D. S., Bennett-Kennett, R. n., Dauskardt, R. H., Gurtner, G. C., Chang, J. n., Fox, P. M., Longaker, M. T. 2021; 9 (1): e3359

    Abstract

    The purpose of this study was to determine the feasibility of using mouse models for translational study of flexor tendon repair and reconstruction.Quantitative data detailing the gross anatomy, biomechanical characteristics, and microscopic structure of the deep digit flexor tendon (DDF) of the mouse hindpaw were obtained. Histological characterization of the DDF and the anatomy of the digit in the mouse hindpaw are detailed. Biomechanical testing determined the load-to-failure, stress, elastic modulus, and the site of tendon failure.In gross anatomy, the origins and insertions of the mouse deep digit flexor tendon are similar to those of the human digit, surrounded by a synovial sheath that is only 1- to 2-cells thick. A neurovascular network runs on each side of the digit outside the synovial sheath, but does not clearly penetrate it. The thickness of the DDF is 0.14 ± 0.03 mm and the width is 0.3 ± 0.03 mm. The thickness of the DDF is less than that of 9-0 nylon needle. The mean failure force of the deep flexor tendon was 2.79 ± 0.53N.The gross anatomy of the mouse hindpaw digit is similar to that of the human digit except for key differences seen in the synovial sheath and vascular supply. The dimensions of the mouse DDF make it challenging to create a clinically translatable repair model using currently available surgical techniques. Despite the similarities between the human and mouse anatomy, and the powerful basic science tools available in murine models, mice are an unreliable model for assessing flexor tendon injury and repair.

    View details for DOI 10.1097/GOX.0000000000003359

    View details for PubMedID 33552814

    View details for PubMedCentralID PMC7859083

  • Impact of COVID-19 on presentation, management, and outcomes of acute care surgery for gallbladder disease and acute appendicitis. World journal of gastrointestinal surgery Farber, O. N., Gomez, G. I., Titan, A. L., Fisher, A. T., Puntasecca, C. J., Arana, V. T., Kempinsky, A., Wise, C. E., Bessoff, K. E., Hawn, M. T., Korndorffer, J. R., Forrester, J. D., Esquivel, M. M. 2021; 13 (8): 859-870

    Abstract

    The ongoing coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted both elective and acute medical care. Data from the early months suggest that acute care patient populations deferred presenting to the emergency department (ED), portending more severe disease at the time of presentation. Additionally, care for this patient population trended towards initial non-operative management.To examine the presentation, management, and outcomes of patients who developed gallbladder disease or appendicitis during the pandemic.A retrospective chart review of patients diagnosed with acute cholecystitis, symptomatic cholelithiasis, or appendicitis in two EDs affiliated with a single tertiary academic medical center in Northern California between March and June, 2020 and in the same months of 2019. Patients were selected through a research repository using international classification of diseases (ICD)-9 and ICD-10 codes. Across both years, 313 patients were identified with either type of gallbladder disease, while 361 patients were identified with acute appendicitis. The primary outcome was overall incidence of disease. Secondary outcomes included presentation, management, complications, and 30-d re-presentation rates. Relationships between different variables were explored using Pearson's r correlation coefficient. Variables were compared using the Welch's t-Test, Chi-squared tests, and Fisher's exact test as appropriate.Patients with gallbladder disease and appendicitis both had more severe presentations in 2020. With respect to gallbladder disease, more patients in the COVID-19 cohort presented with acute cholecystitis compared to the control cohort [50% (80) vs 35% (53); P = 0.01]. Patients also presented with more severe cholecystitis in 2020 as indicated by higher mean Tokyo Criteria Scores [mean (SD) 1.39 (0.56) vs 1.16 (0.44); P = 0.02]. With respect to appendicitis, more patients were diagnosed with a perforated appendix at presentation in 2020 [20% (36) vs 16% (29); P = 0.02] and a greater percentage were classified as emergent cases using the emergency severity index [63% (112) vs 13% (23); P < 0.001]. While a greater percentage of patients were admitted to the hospital for gallbladder disease in 2020 [65% (104) vs 50% (76); P = 0.02], no significant differences were observed in hospital admissions for patients with appendicitis. No significant differences were observed in length of hospital stay or operative rate for either group. However, for patients with appendicitis, 30-d re-presentation rates were significantly higher in 2020 [13% (23) vs 4% (8); P = 0.01].During the COVID-19 pandemic, patients presented with more severe gallbladder disease and appendicitis. These findings suggest that the pandemic has affected patients with acute surgical conditions.

    View details for DOI 10.4240/wjgs.v13.i8.859

    View details for PubMedID 34512909

    View details for PubMedCentralID PMC8394376

  • A Surgical Model for Investigating the Role of Creeping Fat in Intestinal Fibrosis Bauer-Rowe, K. E., Foster, D., Titan, A., Chinta, M., desJardins-Park, H., Griffin, M., Longaker, M. T. ELSEVIER SCIENCE INC. 2020: S50–S51
  • Pancreatic Cancer Associated Fibroblasts (CAF): Under-Explored Target for Pancreatic Cancer Treatment. Cancers Norton, J. n., Foster, D. n., Chinta, M. n., Titan, A. n., Longaker, M. n. 2020; 12 (5)

    Abstract

    Pancreatic cancer is the 4th leading cause of cancer deaths in the United States. The pancreatic cancer phenotype is primarily a consequence of oncogenes disturbing the resident pancreas parenchymal cell repair program. Many solid tumor types including pancreatic cancer have severe tumor fibrosis called desmoplasia. Desmoplastic stroma is coopted by the tumor as a support structure and CAFs aid in tumor growth, invasion, and metastases. This stroma is caused by cancer associated fibroblasts (CAFs), which lay down extensive connective tissue in and around the tumor cells. CAFs represent a heterogeneous population of cells that produce various paracrine molecules such as transforming growth factor-beta (TGF-beta) and platelet derived growth factors (PDGFs) that aid tumor growth, local invasion, and development of metastases. The hard, fibrotic shell of desmoplasia serves as a barrier to the infiltration of both chemo- and immunotherapy drugs and host immune cells to the tumor. Although there have been recent improvements in chemotherapy and surgical techniques for management of pancreatic cancer, the majority of patients will die from this disease. Therefore, new treatment strategies are clearly needed. CAFs represent an under-explored potential therapeutic target. This paper discusses what we know about the role of CAFs in pancreatic cancer cell growth, invasion, and metastases. Additionally, we present different strategies that are being and could be explored as anti-CAF treatments for pancreatic cancer.

    View details for DOI 10.3390/cancers12051347

    View details for PubMedID 32466266

  • The Effect of Surgical Trainee Education on Opioid Prescribing: An International Evaluation. Journal of surgical education Prigoff, J. G., Titan, A. L., Fields, A. C., Shwaartz, C. n., Melnitchouk, N. n., Bleday, R. n., Hawn, M. T., Wiechmann, L. n. 2020

    Abstract

    Up to 6% of opioid naive patients who undergo surgery become chronic opioid users. The aim of this study was to determine if formal opioid prescribing education of general surgery residents is associated with decreased opioid prescribing postoperatively.We surveyed surgery residents at 3 general surgery programs in the United States and 1 in Israel. Residents were divided into 2 groups based on whether or not they received formal opioid prescribing education.Of those surveyed, 107 (50%) responded. 45% of residents had formal opioid prescribing education, which included instructional videos, current literature, and hospital guidelines. For the 4 operations analyzed, residents who received no formal teaching prescribed a higher number of opioids (lumpectomy p = 0.001, open inguinal hernia repair p = 0.004, laparoscopic appendectomy p = 0.007, thyroidectomy p = 0.002). The largest difference in opioid prescribing was seen in "high prescribers," defined as residents prescribing 15 or more opioid pills. For thyroidectomy, 24.4% of residents without formal education prescribed 20 or more oxycodone 5mg pills compared to 0% of residents with formal education. The Israeli cohort was less likely to receive a pain focused education and was also less likely to prescribe opioids to their patients for all 4 procedures evaluated.Although a minority of general surgery residents are receiving an opioid prescribing education, a formal educational program was associated with significantly decreased opioid prescribing. There is a need for a generalizable educational opioid program for surgery residents.

    View details for DOI 10.1016/j.jsurg.2020.04.009

    View details for PubMedID 32446768

  • Patient-reported health literacy scores are associated with readmissions following surgery. American journal of surgery Baker, S. n., Malone, E. n., Graham, L. n., Dasinger, E. n., Wahl, T. n., Titan, A. n., Richman, J. n., Copeland, L. n., Burns, E. n., Whittle, J. n., Hawn, M. n., Morris, M. n. 2020

    Abstract

    Health literacy (HL) impacts medical care. We hypothesized that patients with low HL would have higher readmission rates following surgery.We conducted a prospective, multi-institutional study from 8/2015-6/2017 within the Veterans Affairs (VA) System including veterans who underwent general, vascular, or thoracic surgery. HL was assessed by Brief Health Literacy Screener and stratified into adequate vs. low. Patients were followed for 30 days post-discharge. Multivariable analyses examined correlations and logistic regression models adjusted for covariates.736 patients were enrolled in the study; 98% (n = 722) completed the HL survey. At discharge, 33.2% of patients had low HL. The overall 30-day readmission rate was 16.3%, with a significant difference by HL (Adequate HL: 13.3% vs. Low HL: 22.5%, p < 0.01). After adjusting for clinical and demographic covariates, patients with low HL were 59% more likely to be readmitted (OR = 1.59, 95% CI = 1.02-2.50).Low HL is common among VA surgery patients and is associated with readmission. Future studies should be focused on interventions to target this vulnerable patient population.

    View details for DOI 10.1016/j.amjsurg.2020.06.071

    View details for PubMedID 32682501

  • Elucidating the fundamental fibrotic processes driving abdominal adhesion formation. Nature communications Foster, D. S., Marshall, C. D., Gulati, G. S., Chinta, M. S., Nguyen, A. n., Salhotra, A. n., Jones, R. E., Burcham, A. n., Lerbs, T. n., Cui, L. n., King, M. E., Titan, A. L., Ransom, R. C., Manjunath, A. n., Hu, M. S., Blackshear, C. P., Mascharak, S. n., Moore, A. L., Norton, J. A., Kin, C. J., Shelton, A. A., Januszyk, M. n., Gurtner, G. C., Wernig, G. n., Longaker, M. T. 2020; 11 (1): 4061

    Abstract

    Adhesions are fibrotic scars that form between abdominal organs following surgery or infection, and may cause bowel obstruction, chronic pain, or infertility. Our understanding of adhesion biology is limited, which explains the paucity of anti-adhesion treatments. Here we present a systematic analysis of mouse and human adhesion tissues. First, we show that adhesions derive primarily from the visceral peritoneum, consistent with our clinical experience that adhesions form primarily following laparotomy rather than laparoscopy. Second, adhesions are formed by poly-clonal proliferating tissue-resident fibroblasts. Third, using single cell RNA-sequencing, we identify heterogeneity among adhesion fibroblasts, which is more pronounced at early timepoints. Fourth, JUN promotes adhesion formation and results in upregulation of PDGFRA expression. With JUN suppression, adhesion formation is diminished. Our findings support JUN as a therapeutic target to prevent adhesions. An anti-JUN therapy that could be applied intra-operatively to prevent adhesion formation could dramatically improve the lives of surgical patients.

    View details for DOI 10.1038/s41467-020-17883-1

    View details for PubMedID 32792541

  • Evaluation of Outcomes Following Surgery for Locally Advanced Pancreatic Neuroendocrine Tumors. JAMA network open Titan, A. L., Norton, J. A., Fisher, A. T., Foster, D. S., Harris, E. J., Worhunsky, D. J., Worth, P. J., Dua, M. M., Visser, B. C., Poultsides, G. A., Longaker, M. T., Jensen, R. T. 2020; 3 (11): e2024318

    Abstract

    Although outcome of surgical resection of liver metastases from pancreatic neuroendocrine tumors (PNETs) has been extensively studied, little is known about surgery for locally advanced PNETs; it was listed recently by the European neuroendocrine tumor society as a major unmet need.To evaluate the outcome of patients who underwent surgery for locally aggressive PNETs.This retrospective single-center case series reviewed consecutive patients who underwent resection of T3/T4 PNETs at a single academic institution. Data collection occurred from 2003 to 2018. Data analysis was performed in August 2019.Disease-free survival (primary outcome) and overall mortality (secondary outcome) were assessed with Kaplan-Meier analysis. Recurrence risk (secondary outcome, defined as identification of tumor recurrence on imaging) was assessed with Cox proportional hazard models adjusting for covariates.In this case series, 99 patients with locally advanced nondistant metastatic PNET (56 men [57%]) with a mean (SEM) age of 57.0 (1.4) years and a mean (SEM) follow-up of 5.3 (0.1) years underwent surgically aggressive resections. Of those, 4 patients (4%) underwent preoperative neoadjuvant treatment (including peptide receptor radionuclide therapy and chemotherapy); 18 patients (18%) underwent pancreaticoduodenectomy, 68 patients (69%) had distal or subtotal pancreatic resection, 10 patients (10%) had total resection, and 3 patients (3%) had other pancreatic procedures. Additional organ resection was required in 86 patients (87%): spleen (71 patients [71%]), major blood vessel (17 patients [17%]), bowel (2 patients [2%]), stomach (4 patients [4%]), and kidney (2 patients [2%]). Five-year disease-free survival was 61% (61 patients) and 5-year overall survival was 91% (91 patients). Of those living, 75 patients (76%) had an Eastern Cooperative Oncology Group score of less than or equal to 1 at last followup. Lymph node involvement (HR, 7.66; 95% CI, 2.78-21.12; P < .001), additional organ resected (HR, 6.15; 95% CI, 1.61-23.55; P = .008), and male sex (HR, 3.77; 95% CI, 1.68-8.97; P = .003) were associated with increased risk of recurrence. Functional tumors had a lower risk of recurrence (HR, 0.23; CI, 0.06-0.89; P = .03). Required resection of blood vessels was not associated with a significant increase recurrence risk.In this case series, positive lymph node involvement and resection of organs with tumor involvement were associated with an increased recurrence risk. These subgroups may require adjuvant systemic treatment. These findings suggest that patients with locally advanced PNETs who undergo surgical resection have excellent disease-free and overall survival.

    View details for DOI 10.1001/jamanetworkopen.2020.24318

    View details for PubMedID 33146734

  • Growth Factor Delivery to a Bovine Defect Using Leukocyte -Rich Platelet-Rich Concentrates on a Hyaluronic Acid Scaffold. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association Titan, A., Schar, M., Hutchinson, I., Demange, M., Chen, T., Rodeo, S. 2019

    Abstract

    PURPOSE: To determine if (1) Human L-PRP or (2) L-PRF delivered on a HA scaffold at a bovine chondral defect, a simulated cartilage tear interface, in vitro would improve tissue formation based on biomechanical, histological, and biochemical measures.METHODS: L-PRF and L-PRP was prepared from 3 healthy volunteer donors which was delivered in conjunction with Hyaluronic acid (HA scaffolds) to defects created in full thickness bovine cartilage plugs harvested from bovine femoral condyle and trochlea. Specimens were cultured in vitro for up to 42 days. Treatment groups included an HA scaffold alone and scaffolds containing L-PRF or L-PRP. Cartilage repair was assessed using biomechanical testing, histology, DNA quantification, and measurement of sulfated glycosaminoglycan (sGAG) and collagen content at 28 and 42 days.RESULTS: L-PRF elicited the greatest degree of defect filling and improvement in other histological measures. L-PRF treated specimens also had the greatest cellularity when compared to L-PRP and control at day 28 (560.4 vs. 191.4 vs. 124.2, p=00.15); at day 48 there remains a difference though not significant between L-PRF vs L-PRP, (761.1 vs 589.3, p=0.219) . L-PRF had greater collagen deposition when compared to L-PRP at day 42 (40.1 vs 16.3, p< 0.0001). L-PRF had significantly higher maximum interfacial strength compared to the control at day 42 (10.92 N vs 0.66 N, p=0.015), but had no significant difference compared to L-PRP (10.92 N vs 6.58, p=0.536). L-PRP facilitated a greater amount of sGAG production at day 42 when compared to L-PRF (15.9 vs. 4.3, p=0.009).CONCLUSIONS: Delivery of leukocyte rich platelet concentrates in conjunction with a HA scaffold may allow for improvements in cartilage healing through different pathways. L-PRF was not superior to L-PRP in its biomechanical strength suggesting that both treatments may be effective in improving biomechanical strength of healing cartilage through different pathways.

    View details for DOI 10.1016/j.arthro.2019.12.004

    View details for PubMedID 31862290

  • A fine balance in tendon healing. Nature cell biology Titan, A. L., Longaker, M. T. 2019

    View details for DOI 10.1038/s41556-019-0432-0

    View details for PubMedID 31768049

  • Endogenous Breast Cancer Shows Clonal Proliferation of Cancer Associated Fibroblasts at Primary Tumor and Metastatic Sites Foster, D. S., Chinta, M., Nguyen, A. T., Salhotra, A., Ransom, R., Jones, R., Titan, A. L., Mascharak, S., Norton, J. A., Longaker, M. T. ELSEVIER SCIENCE INC. 2019: S262
  • Reducing Postoperative Opioid Prescribing Through Education: A Multicenter Survey of Surgical Residents Prigoff, J. G., Fields, A. C., Titan, A. L., Hawn, M. T., Jambhekar, A., Melnitchouk, N., Bleday, R., Wiechmann, L. ELSEVIER SCIENCE INC. 2019: S249
  • Role of the Skeletal Stem Cell in Achilles Tendon to Bone Interface Healing Titan, A. L., Jones, R., Salhotra, A., Robertson, K. S., Foster, D., Menon, S., Murphy, M., Lucero, G. V., Chan, C. K., Longaker, M. T. ELSEVIER SCIENCE INC. 2019: S228–S229
  • Effect of Mechanical Loading on Clonality of Injured Flexor Tendons after Repair Titan, A. L., Foster, D., Jones, R., Salhotra, A., Nguyen, A. T., Longaker, M. T. ELSEVIER SCIENCE INC. 2019: S221
  • Fibroblast Proliferation in Wound Healing Is Clonal and Focal Adhesion Kinase-Dependent Chinta, M., Foster, D., Nguyen, A. T., Salhotra, A., Ransom, R. C., Jones, R., Titan, A. L., Marshall, C., Mascharak, S., Longaker, M. T. ELSEVIER SCIENCE INC. 2019: S223
  • Cancer-Associated Fibroblasts Persist but Show Decreased Fibroblast Activation Protein Expression after Neoadjuvant Chemotherapy in Human Pancreatic Ductal Adenocarcinoma Foster, D. S., Nguyen, A. T., Chinta, M., Titan, A. L., Salhotra, A., Jones, R., Mascharak, S., Norton, J., Longaker, M. T. ELSEVIER SCIENCE INC. 2019: S257–S258
  • Tumors Co-Opt Fibroblast Wound Healing Capacity Foster, D. S., Mascharak, S., Nguyen, A. T., Chinta, M., Salhotra, A., Titan, A. L., Jones, R., da Silva, O., Norton, J. A., Longaker, M. T. ELSEVIER SCIENCE INC. 2019: S231–S232
  • Perioperative opioid use and pain-related outcomes in the Veterans Health Administration. American journal of surgery Hernandez-Boussard, T., Graham, L. A., Carroll, I., Dasinger, E. A., Titan, A. L., Morris, M. S., Hawn, M. T. 2019

    Abstract

    Understanding variation in perioperative opioid exposure and its effect on patients' outcomes is critical for pain management. This study characterized perioperative exposure to morphine and its association with postoperative pain and 30-day readmissions. We utilized nationwide Veterans Healthcare Administration (VHA) data on four high-volume surgical procedures, 2007-2014. We identified 235,239 Veterans undergoing orthopedic, general, or vascular surgery; 5.4% high trajectories (116.1 OME/Day), 53.2% medium trajectories (39.7 OME/Day), and 41.4% low trajectories (19.1 OME/Day). Modeled estimates suggest that patients in the high OME group had higher risk of a pain-related readmission (OR: 1.59; CI: 1.39, 1.83) compared to the low OME trajectory. Yet when stratified by pain trajectory, patients with high pain and high OME had lower risk of a pain-related readmission compared to patients in the high pain low OME group (OR: 0.76, CI: 0.62, 0.94). In conclusion, patients receiving high perioperative OME are more likely to return to care for pain-related problems. This study highlights opportunities to reduce the amount of prescriptions opioids in the communities.

    View details for DOI 10.1016/j.amjsurg.2019.06.022

    View details for PubMedID 31280840

  • Caring for Caregivers - Resident Physician Health and Wellbeing. Journal of surgical education Baiu, I. n., Titan, A. n., Kin, C. n., Spain, D. A. 2019

    Abstract

    There is a national epidemic of physician burnout and serious concerns exist regarding the well-being of future physicians. This project seeks to address resident physician health, by creating a sense of support and community during training, as a method to target one of the many facets of burnout.We created a program that allows residents who fall ill to receive a health package, delivered to work or home, consisting of essential medications, vitamins, nutrition, and hydration. The recipients were asked to answer a short survey regarding their experience.Stanford Health Care, Department of Surgery, Division of General Surgery, Palo Alto California.Eighteen packages have been delivered since the start of the project. One hundred percent of residents agree that this program fulfills an otherwise unmet need in residency. Similarly, all felt that the supplies they received helped them recover faster. The majority (83%) of the packages were requested by colleagues of the ill residents.We present an innovative project aimed at improving resident physician health, fostering a feeling of support, and helping to reduce resident burnout. This is the first report of a program of this kind and we hope that it incentivizes a broader discussion and implementation of similar initiatives in other residency programs across the country.

    View details for DOI 10.1016/j.jsurg.2019.08.007

    View details for PubMedID 31494061

  • Patient expectations for recovery after elective surgery: a common-sense model approach. Journal of behavioral medicine Gehring, M. B., Lerret, S. n., Johnson, J. n., Rieder, J. n., Nelson, D. n., Copeland, L. n., Titan, A. n., Hawn, M. n., Morris, M. n., Whittle, J. n., Burns, E. n. 2019

    Abstract

    Patient perceptions of the causes of preoperative symptoms, expected impact of surgery on symptoms and anticipated timeline of recovery are likely to affect the risk of readmission following elective surgical procedures. However, these perceptions have not been studied. A qualitative study was designed to explore these perceptions, using the common-sense model of self-regulation (CSM) as the conceptual framework. CSM is grounded in illness representations, describing how patients make sense of changes in physical well-being (e.g. symptoms) and develop and assess management plans. It also establishes a broader framework for examining patients' a priori expectations and timelines for outcomes based on comparisons to prior experiences and underlying self-prototypes, or "Self as Anchor". A convenience sample of 14 patients aged 56-81 who underwent elective surgery was recruited. Semi-structured interviews informed by the CSM were completed on the day of discharge. Content analysis with deductive coding was used, and emerging themes were fit to components of the CSM, including the five domains of Illness Representations-identity, cause, timeline, control, and consequences. Two additional themes, outlook (toward the health care system, providers and recovery efforts), and motivation (external or internal for recovering), relate to self-prototypes, expectations for outcomes, and search for coherence. Misattribution of symptoms, unrealistic expectations for outcomes (e.g. expecting complete resolution of symptoms unrelated to the surgical procedure) and timelines for recovery (unrealistically short), and the (baseline) "normal healthy self" as distinct from the (temporarily) "sick self" were recurrent themes. Findings suggest that patient perceptions and the actual recovery process may be misaligned. The results underscore the importance of assessing patients' perceptions and expectations, actively engaging patients in their own healthcare, and providing adequate support during the transition to home.

    View details for DOI 10.1007/s10865-019-00097-2

    View details for PubMedID 31512105

  • The influence of hormone replacement therapy on lung cancer incidence and mortality. The Journal of thoracic and cardiovascular surgery Titan, A. L., He, H. n., Lui, N. n., Liou, D. n., Berry, M. n., Shrager, J. B., Backhus, L. M. 2019

    Abstract

    Data regarding the effects of hormone replacement therapy (HRT) on non-small cell lung cancer (NSCLC) are mixed. We hypothesized HRT would have a protective benefit with reduced NSCLC incidence among women in a large, prospective cohort.We used data from the multicenter randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2001). Participants were women aged 50 to 74 years followed prospectively for up to 13 years for cancer screening. The influence of HRT on the primary outcome of NSCLC incidence and secondary outcomes of all-cause and disease-specific mortality were assessed with Kaplan-Meier analysis and Cox proportional hazard models adjusting for covariates.In the overall cohort of 75,587 women, 1147 women developed NSCLC after a median follow-up of 11.5 years. HRT use was characterized as 49.4% current users, 17.0% former users, and 33.6% never users. Increased age, smoking, comorbidities, and family history were associated with increased risk of NSCLC. On multivariable analysis, current HRT use was associated with reduced risk of NSCLC compared with never users (hazard ratio, 0.80; 95% confidence interval, 0.70-0.93; P = .009). HRT or oral contraception use was not associated with significant differences in all-cause mortality or disease-specific mortality.These data represent among the largest prospective cohorts suggesting HRT use may have a protective effect on the development of NSCLC among women; the physiological basis of this effect merits further study; however, the results may influence discussion surrounding HRT use in women.

    View details for DOI 10.1016/j.jtcvs.2019.10.070

    View details for PubMedID 31866083

  • Flexor Tendon: Development, Healing, Adhesion Formation, and Contributing Growth Factors. Plastic and reconstructive surgery Titan, A. L., Foster, D. S., Chang, J. n., Longaker, M. T. 2019; 144 (4): 639e–647e

    Abstract

    Management of flexor tendon injuries of the hand remains a major clinical problem. Even with intricate repair, adhesion formation remains a common complication. Significant progress has been made to better understand the mechanisms of healing and adhesion formation. However, there has been slow progress in the clinical prevention and reversal of flexor tendon adhesions. The goal of this article is to discuss recent literature relating to tendon development, tendon healing, and adhesion formation to identify areas in need of further research. Additional research is needed to understand and compare the molecular, cellular, and genetic mechanisms involved in flexor tendon morphogenesis, postoperative healing, and mechanical loading. Such knowledge is critical to determine how to improve repair outcomes and identify new therapeutic strategies to promote tissue regeneration and prevent adhesion formation.

    View details for DOI 10.1097/PRS.0000000000006048

    View details for PubMedID 31568303

  • A Clearing Technique to Enhance Endogenous Fluorophores in Skin and Soft Tissue. Scientific reports Foster, D. S., Nguyen, A. T., Chinta, M. n., Salhotra, A. n., Jones, R. E., Mascharak, S. n., Titan, A. L., Ransom, R. C., da Silva, O. L., Foley, E. n., Briger, E. n., Longaker, M. T. 2019; 9 (1): 15791

    Abstract

    Fluorescent proteins are used extensively in transgenic animal models to label and study specific cell and tissue types. Expression of these proteins can be imaged and analyzed using fluorescent and confocal microscopy. Conventional confocal microscopes cannot penetrate through tissue more than 4-6 μm thick. Tissue clearing procedures overcome this challenge by rendering thick specimens into translucent tissue. However, most tissue clearing techniques do not satisfactorily preserve expression of endogenous fluorophores. Using simple adjustments to the BABB (Benzoic Acid Benzyl Benzoate) clearing methodology, preservation of fluorophore expression can be maintained. Modified BABB tissue clearing is a reliable technique to clear skin and soft tissue specimens for the study of dermal biology, wound healing and fibrotic pathologies.

    View details for DOI 10.1038/s41598-019-50359-x

    View details for PubMedID 31673001

  • Management of Ileal Neuroendocrine Tumors with Liver Metastases. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract Fisher, A. T., Titan, A. L., Foster, D. S., Worth, P. J., Poultsides, G. A., Visser, B. C., Dua, M. M., Norton, J. A. 2019

    Abstract

    Assessment of treating metastatic ileal neuroendocrine tumors (NETs) with complete resection of primary tumor, nodal and liver metastases, plus administration of long-acting somatostatin analogues (SSAs).A prospective database was queried for patients with ileal or pancreatic NETs with pathology-confirmed liver metastases and tumor somatostatin receptors. Patients did not have MEN-1 and had no previous treatment. The impacts of SSA treatment on the primary outcome of survival and secondary outcome of progression-free survival were assessed with Kaplan-Meier analysis. Log rank test was used to compare overall and progression-free survival among groups.Seventeen ileal NET patients and 36 pancreatic NET patients who underwent surgical resection between 2001 and 2018, who had pathology-confirmed liver metastases and confirmed tumor somatostatin receptors, did not have MEN-1, and had no previous treatment were identified. Median follow-up for patients with ileal NETs was 80 months (range 0-197 months) and 32 months (range 1-182 months) for pancreatic NETs. Five-year survival was 93% and 72% for ileal and pancreatic NET, respectively. Progression-free 5-year survival was 70% and 36% for ileal and pancreatic NET, respectively. Overall 5-year survival for pNETs was greater in those patients treated with SSA (79%) compared to those who underwent surgery alone (34%, p < 0.01). The average ECOG score was low for surviving patients with ileal (0.15) and pancreatic NET (0.73) indicating a good quality of life.Resection of primary lymph node and liver metastatic ileal or pancreatic NETs followed with continued SSAs is associated with an excellent progression-free and overall survival and minimal side effects.

    View details for DOI 10.1007/s11605-019-04309-7

    View details for PubMedID 31346887

  • Clinical Trigonometry: Right Hepatic Trisegmentectomy After Radiation Trisegmentectomy for Hepatocellular Carcinoma DIGESTIVE DISEASES AND SCIENCES Titan, A. L., Devereaux, K., Louie, J. D., Poultsides, G. A. 2018; 63 (6): 1419–23

    View details for PubMedID 29119415

  • Homeless Status, Postdischarge Health Care Utilization, and Readmission After Surgery. Medical care Titan, A. n., Graham, L. n., Rosen, A. n., Itani, K. n., Copeland, L. A., Mull, H. J., Burns, E. n., Richman, J. n., Kertesz, S. n., Wahl, T. n., Morris, M. n., Whittle, J. n., Telford, G. n., Wilson, M. n., Hawn, M. n. 2018; 56 (6): 460–69

    Abstract

    Homeless Veterans are vulnerable to poor care transitions, yet little research has examined their risk of readmission following inpatient surgery. This study investigates the predictors of surgical readmission among homeless relative to housed Veteran patients.Inpatient general, vascular, and orthopedic surgeries occurring in the Veterans Health Administration from 2008 to 2014 were identified. Administrative International Classification of Diseases, Ninth Revision, Clinical Modification codes and Veterans Health Administration clinic stops were used to identify homeless patients. Bivariate analyses examined characteristics and predictors of readmission among homeless patients. Multivariate logistic models were used to estimate the association between homeless experience and housed patients with readmission following surgery.Our study included 232,373 surgeries: 43% orthopedic, 39% general, and 18% vascular with 5068 performed on homeless patients. Homeless individuals were younger (56 vs. 64 y, P<0.01), more likely to have a psychiatric comorbidities (51.3% vs. 19.4%, P<0.01) and less likely to have other medical comorbidities such as hypertension (57.1% vs. 70.8%, P<0.01). Homeless individuals were more likely to be readmitted [odds ratio (OR), 1.43; confidence interval (CI), 1.30-1.56; P<0.001]. Discharge destination other than community (OR, 0.57; CI, 0.44-0.74; P<0.001), recent alcohol abuse (OR, 1.45; CI, 1.15-1.84; P<0.01), and elevated American Society Anesthesiologists classification (OR, 1.86; CI, 1.30-2.68; P<0.01) were significant risk factors associated with readmissions within the homeless cohort.Readmissions are higher in homeless individuals discharged to the community after surgery. Judicious use of postoperative nursing or residential rehabilitation programs may be effective in reducing readmission and improving care transitions among these vulnerable Veterans. Relative costs and benefits of alternatives to community discharge merit investigation.

    View details for PubMedID 29746348

  • Tendinopathy: Investigating the Intersection of Clinical and Animal Research to Identify Progress and Hurdles in the Field. JBJS reviews Titan, A., Andarawis-Puri, N. 2016; 4 (10)

    View details for DOI 10.2106/JBJS.RVW.15.00088

    View details for PubMedID 27792676

  • The Choice Between Total Hip Arthroplasty and Arthrodesis in Adolescent Patients: A Survey of Orthopedic Surgeons JOURNAL OF ARTHROPLASTY Kelman, M. G., Studdert, D. M., Callaghan, J. J., Farid, M. S., Titan, A. L., Dietz, F. R. 2016; 31 (1): 70-75

    Abstract

    For adolescent patients with end-stage hip disease, the choice between total hip arthroplasty (THA) and arthrodesis is complex; the clinical evidence is not definitive, and there are difficult trade-offs between clear short-term benefits from THA and uncertain long-term risks. We surveyed nearly 700 members of the Pediatric Orthopedic Society of North America and the American Association of Hip and Knee Surgeons. Respondents chose between a recommendation of THA or arthrodesis in four clinical vignettes. A clear majority of surgeons recommended THA in two of the vignettes, however opinion was somewhat divided in one vignette (overweight adolescent) and deeply divided in another (adolescent destined for manual labor job). Across all vignettes, recommendations varied systematically according to surgeons' age and their attitudes regarding tradeoffs between life stages.

    View details for DOI 10.1016/j.arth.2015.07.020

    View details for Web of Science ID 000366677000014

    View details for PubMedID 26298281

  • Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels ACTA BIOMATERIALIA Ma, K., Titan, A. L., Stafford, M., Zheng, C. H., Levenston, M. E. 2012; 8 (10): 3754-3764

    Abstract

    Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) for articular cartilage and fibrocartilage tissue engineering, with each material offering distinct advantages and disadvantages. Attempting to produce a gel scaffold exhibiting beneficial characteristics of both materials, we fabricated fibrin/alginate blended hydrogels at various blend ratios and evaluated the gel morphology, mechanical properties and their support for BM-MSC chondrogenesis. Results show that when the fibrin/alginate ratio decreased, the fibrin architecture transitioned from uniform to interconnected fibrous and finally to disconnected islands against an alginate background, with opposing trends in the alginate architecture. Fibrin maintained gel extensibility and promoted cell proliferation, while alginate improved the gel biostability and better supported glycosaminoglycan and collagen II production and chondrogenic gene expression. Blended gels had physical and biological characteristics intermediate between fibrin and alginate. Of the blends examined, FA 40:8 (40 mg ml(-1) fibrinogen blended with 8 mg ml(-1) alginate) was found to be the most appropriate group for future studies on tension-driven BM-MSC fibrochondrogenesis. As BM-MSC differentiation appeared to vary between fibrin and alginate regions of blended scaffolds, this study also highlighted the potential to develop spatially heterogeneous tissues through manipulating the heterogeneity of scaffold composition.

    View details for DOI 10.1016/j.actbio.2012.06.028

    View details for Web of Science ID 000309301400022

    View details for PubMedID 22750738

    View details for PubMedCentralID PMC3429695