40.04 The Emergence of Video Technology as an Important Adjunct to Surgical Education

Posted on December 22, 2014

K. M. McKendy1, L. Lee1, J. R. Grushka1, A. N. Beckett1, K. A. Khwaja1, P. Fata1, T. S. Razek1, D. L. Deckelbaum1  1McGill University,General Surgery / Surgery,Montreal, QC, Canada

Introduction:

When preparing to perform a case in the operating room, surgical residents often review the steps of procedures using surgical atlases.  Videos of surgical procedures are an emerging teaching modality.  While video footage is more readily available for laparoscopic cases, high quality videos of open surgical cases are scarce.  Moreover, many videos are created without using rigorous methodology.  The aim of our study was to validate the use of instructional videos as an educational tool in surgery.  We began by looking at open tracheostomy, since this procedure is relatively straightforward and frequently performed at our institution.

Methods:

Cognitive task analysis (CTA) was used to elaborate a list of the key steps of an open tracheostomy.  Six experts were interviewed and asked to describe how they perform an open tracheostomy.  The interviews were transcribed and analyzed, and a list of the 10 key steps and each of their sub-steps was elaborated.  The experts were then asked to rate the importance of each sub-step using a Likert scale.  An instructional video of an open tracheostomy case was then created, underscoring the steps and decision-making points emphasized by the expert panel using CTA.  To establish proof of concept of the utility of these instructional videos, a pilot study was conducted with PGY-1 and 2 surgical residents.  The residents were randomized to either view the video or read a text of the video narration, and then tested on their knowledge of the critical steps of the procedure. Critical steps were identified through CTA using a weighted scale.  Results were analyzed using an independent sample t-test.  For additional feedback on the quality and utility of the video, those randomized to the video group were subsequently asked to complete a questionnaire on its educational value.

Results:

64 PGY-1 and 2 surgical residents from all surgical subspecialties were enrolled in the study.  Of these, 40 completed the test: 20 residents from the video group and 20 from the text group.  While there was no significant difference between the average scores of the video and text group, 93% of residents who were randomized to the video group agreed that the video was a useful learning tool and that it helped prepare them for the operating room.  In addition, 92% agreed or strongly agreed that they would watch the video rather than reviewing the content in a textbook, and 100% felt that their knowledge of relevant anatomy had improved with the video.

Conclusion:

This study illustrates the use of CTA in the creation of an instructional surgical video on open tracheostomy.  The results of this pilot study suggest that surgical videos are an excellent adjunct to the educational armamentarium of surgical trainees.

40.05 Working at home: Results from a multi-center survey of surgery & internal medicine residents

Posted on December 22, 2014

C. Thiessen1, L. S. Lehmann3, F. G. Javier5, M. J. Erlendson5, L. A. Skrip4, M. R. Mercurio2, K. A. Davis1  1Yale University School Of Medicine,Department Of Surgery,New Haven, CT, USA 2Yale University School Of Medicine,Department Of Pediatrics,New Haven, CT, USA 3Brigham And Women’s Hospital,Department Of Medicine,Boston, MA, USA 4Yale School Of Public Health,Department Of Epidemiology Of Microbial Diseases,New Haven, CT, USA 5Yale University School Of Medicine,New Haven, CT, USA

Introduction:  With the spread of electronic medical records, residents have increasing opportunities to do patient care work at home. ACGME guidance specifies that patient work at home should count toward the resident hour limits. This study evaluated the amount and type of patient care work residents report performing at home, and why they do so.

Methods:  Residents at 26 general surgery and internal medicine residency programs were invited to take an anonymous online survey about work at home and duty hours. Programs were selected to represent a range of geographic location, size, and academic status. The survey was administered in May and June 2014. When answering questions about work at home, residents were instructed to think only about patient care and to exclude time spent “studying, preparing for presentations, or doing research.” Our results were analyzed with standard descriptive statistics in SAS 9.3. We used multivariate logistic regression to determine if demographic variables including specialty and training level were associated with reporting working at home.

Results: Of 1591 contacted residents, 535 completed the survey (response rate 34%). Sixty percent of all respondents were men, 60% were Caucasian, 56% were < 30 years old, and 42% were general surgery residents. Respondent level included PGY1 (38%), PGY2 (28%), PGY3 (22%), and PGY4-5 and research years (12%). Most residents reported performing patient care work at home, but did not count this toward their duty hours (88%). Residents worked at home an average of 1-2 hours (35%), 2-5 hours (36%), 5-10 hours (14%), or >10 hours (4%) per week. Work at home included: checking lab and results (92%), reading charts to prepare for a new rotation (87%), reviewing patient vitals (75%), and talking to other residents or attendings (72%). Surgery residents also frequently reviewed charts for upcoming cases (94%) and completed operative reports (65%). Curiosity about patient outcomes (78%), desire to leave the hospital (74%), comfort (66%), and increased time with family (61%) were the most important reasons for working at home. Thirty percent of residents explicitly did work at home to avoid counting it as duty hours. On univariate and multivariate analysis there was no significant relationship between gender, age, race, specialty, or level and likelihood of reporting working at home.

Conclusion: Electronic medical records allow the majority of residents to shift some patient care work from the hospital to home. Most residents in our study reported not recording this time as duty hours despite ACGME guidance to the contrary. Our results indicate that residents’ sense of responsibility for their patients continues after they leave the hospital, perhaps mitigating concerns about a “shift-work mentality.” Given the prevalence of work at home, further research should assess its impact on patient care, resident education, and quality of life.

 

40.06 The Impact of a Targeted CDI Intervention on the Documentation Patterns of Surgery Residents

Posted on December 22, 2014

D. Jeffcoach1, T. La Charite1, P. B. Barlow1, C. Powell1, M. Phillips1, M. Goldman1  1University Of Tennessee Medical Center – Knoxville,Surgery,Knoxville, TN, USA

Introduction:
Surgical resident education has become more complex. Challenges include meeting the Next Accreditation System education milestones, the national implementation of the Patient Protection and Affordable Care Act (PPACA), and decreasing resident education funding. In addition, physician reimbursement for surgical procedures has declined over the last decade. To address these concerns we developed a training intervention focused on improving patient documentation. We hypothesize that implementing an individualized targeted clinical documentation intergrety intervention for surgical residents would improve documentation patterns. Success was defined as an increase in geometric mean length of stay, case mix index and reimbursement.

Methods:
With IRB approval a prospective case control study was performed using an individualized targeted intervention. Charts were reviewed for all patients discharged from four surgical services over a one month period. Patient demographics, length of stay (LOS), geometric mean length of stay (GMLOS), case mix index (CMI) and reimbursement was collected. All general surgery residents underwent a personalized thirty-minute intervention reviewing the quality of their documentation using current medical documentation practices. After the intervention a subsequent sample of surgical patients were evaluated using the same endpoints.

Results:
All general surgical residents participated in the study (n = 29). In the pre-intervention group there were 396 patient encounters and 328 in the post-intervention group.  Baseline comparisons were made using Mann-Whitney U and chi-square tests of independence. The proportion of patients representing each service was not statistically different between months. Actual LOS remained constant between groups (4.0, IQR 5.0 vs. 4.00, IQR 5.00; p=0.970). Independent t-tests on primary endpoints found that the disparity between GMLOS and the patient’s actual LOS was narrowed by nearly a full day in the post-intervention month (M = 1.09, SD = 8.17) compared to the pre-intervention month (M = 1.90, SD = 6.69), p=0.134. CMI also increased (CMI=2.25, SD=1.94 vs. CMI=2.47, SD=2.32; p=0.165), as did reimbursement, $11,834 (SD=$12,744) vs. $12,790 (SD=$14,108), p=0.333.

Conclusion:
While reimbursement increased nearly $1,000 per case, GMLOS increased by one day, and the overall CMI increased, statistical significance was confounded by the wide variance amongst surgical patients. These parameters are vital to hospital fiscal solvency and we consider any improvement a success. In addition to improved resident awareness of accurate documentation, we were able to use this data to negotiate increases in resident complement funded by our hospital. This approach is valuable to both prepare residents for successful practice as well as validate their financial benefit to hospital systems as resources for resident education continue to decrease.
 

40.07 Management of Vascular Trauma by Senior Surgical Residents: Perception Does Not Equal Reality.

Posted on December 22, 2014

M. W. Bowyer1, S. A. Shackelford1,2, E. Garofalo1,2, K. Pugh2, C. Mackenzie2  1Uniformed Services University Of The Health Sciences,Norman M. Rich Department Of Surgery,Bethesda, MD, USA 2University Of Maryland,Baltimore, MD, USA

Introduction: Experience with the management of vascular trauma by senior surgical residents is limited. When queried about their understanding of anatomy and ability to perform specific vascular exposures, residents express a moderately high level of confidence. We hypothesized that this perception does not equal reality. 

Methods: 42 senior surgical residents participating in an ongoing validation study of the Advanced Surgical Skills for Exposures in Trauma (ASSET) course were asked to self-assess their baseline (pre-course) confidence of their understanding of the anatomy required to perform, and their ability to perform exposures of the Axillary (AA), Brachial (BA), and Femoral (FA) Arteries, as well as Lower Extremity Fasciotomy (LEF) using a 5 point Likert scale. The residents then performed the 4 procedures on a cadaver model and were scored in real time by pre-trained trauma experts using both a global assessment (5 point Likert scale) of "understanding of anatomy" and "resident is ready to perform", as well an overall numerical score (1-100) of the performance. Statistical analysis was performed using the student t-test with α set at p < 0.05.

Results: As seen in the table, residents consistently rated their understanding of anatomy and their ability to perform the 4 procedures higher than the expert evaluators ultimately scored them.  This was especially pronounced for the lower extremity for both FA exposure and lower extremity fasciotomy. The average global numerical scores for the 4 procedures was between 57 and 66 out of 100 points.

Conclusion: The findings suggest that senior residents are ill-prepared to perform the studied exposures for vascular trauma, and that they have an unwarranted confidence in both their understanding of the anatomy and the ability to perform these procedures. Perception clearly does meet reality in preparing these trainees to perform as advertised, and future curricular offerings and evaluation should address this gap.

 

40.08 Impact of Advanced Practice Providers (NPs and PAs) on Surgical Residents’ Critical Care Experience

Posted on December 22, 2014

S. A. Kahn1, S. Davis1, C. F. Banes1, B. Dennis1, A. K. May1, O. Gunter1  1Vanderbilt University Medical Center,Trauma And Surgical Critical Care,Nashville, TN, USA

Introduction:  Teaching hospitals often employ Advanced Practice Providers (nurse practioners and physician assistants, or APPs) to counteract the restricted work-hours decrease in resident manpower. With the ever growing utilization of APPs in labor intense areas, such as intensive care units (ICUs), APPs are likely to play a significant role in resident education and experience. No studies have been conducted to investigate the direct role an APP plays on the work and training experience of a surgical resident in the ICU. 
 

Methods:  This was an IRB approved survey of surgical residents in the United States. The survey was distributed via email to residents in ACGME-accredited general surgery residencies through their program coordinators. In addition to demographics, residency and ICU characteristics, residents were asked about effects of APPs on various domains of patient care, work flow, and educational experience. Ordinal regression analysis was used to determine predictors of resident perception.
 

Results: 354 of 1178 residents responded to the survey (30%). Of these respondents, 72% were from large-university programs, while 79.3% worked in closed or semi-closed ICUs. APPs worked in 81.6% of ICUs. APPs performed procedures in 73.6% of ICUs, for which residents reported a mild negative effect on their training (score 40/100 [IQR 25.5,55.5] scale:50=neutral, <50=detracts,>50=enhances training). Some residents felt that nurses preferentially calling APPs for patient care issues interfered with education (17%) and residents' ability to follow patients (12%). Most residents reported positive effects of APPs, such as reduced resident work load (79.8%), teaching protocols/guidelines (60.3%), enhanced patient care (60.3%), and enhanced communication (50.5%). When asked how APPs affected their overall ICU experience, 48.4% reported positive effects, 20.6% reported “no effect,” and 31% reported detrimental effects. Nurses calling APPs instead of residents for patient care increased the perception of APPs causing overall detrimental effects to ICU experience (OR 3.7, CI 1.5-9.1), while a view that APPs enhanced the resident-attending relationship was protective against detrimental effects (OR 0.91, CI 0.89-0.93). 

Conclusion: Most residents feel that APPs have a positive or neutral effect on their ICU experience. A minority of residents perceive that APPs detract from training, particularly those who feel excluded when nurses preferentially contact APPs with patient care issues.  APPs have the potential to enhance training and foster a positive ICU experience, as reflected in many of the resident survey responses. Strategies to maintain direct nurse and resident communication might preserve residents' perception of the educational value of APPs.

 

40.09 Using Surgical Bootcamp to Teach Core Entrustable Professional Activities for Entering Residency

Posted on December 22, 2014

V. M. Jones1, E. X. Chen1, J. L. Raque1, E. Sutton1  1University Of Louisville,Department Of Surgery,Louisville, KY, USA

Introduction: Surgical residents are given autonomy early in their training, often with limited direct supervision. The Core Entrustable Professional Activities for Entering Residency (CEPAER, Figure 1) were developed to reduce the gap “between what new residents do without supervision and what they have been documented as competent to do without supervision.” We describe use of a surgical bootcamp to document achievement of CEPAER in medical students entering surgical residency.

Methods: Prior to the course, a focus group about course expectations, including a pre-test of confidence and knowledge about communication and patient care was given. Medical students pursuing surgical residency then completed the 4-week course in the spring of their fourth year. The course featured didactic and hands on instruction in airway management, venous access, surgical technique, obtaining informed consent, radiography interpretation, and obstetric, orthopedic, and plastic surgery emergencies. Educational tools used to teach the course included part task trainers, patient simulators, standardized patients, and direct observation/instruction. Students also participated in the MedEdPortal course “Death on the Wards” and a mock call program administered by two registered nurses. A post course focus group and posttest was conducted. Student achievement of the CEPAER was documented by faculty daily.

Results:We were able to document competency, defined as direct observation of skill without supervision, for all EPAs except numbers 6, 7, and 13, for a total of 10/13 EPAs (77%). Four of nine students were not able to complete the Advanced Cardiac Life Support (ACLS) algorithm (representing EPA 10) for a standardized patient simulation involving myocardial infarction. A two-day refresher course in ACLS was then given in which all students successfully demonstrated competence.

The “Death on the Wards” course significantly increased student confidence and knowledge regarding communication and administrative responsibilities surrounding patient death.  The average assessment of confidence prior to the workshop was 19.78 ± 4.41 (SEM 1.47). After bootcamp, the average was 31.56 ± 4.48 (SEM 1.49) (p < 0.01).  The average assessment of knowledge prior to the workshop was 16.11 ± 3.95 (SEM 1.32). After bootcamp, the average was 31.33 ± 6.12 (SEM 2.04) (p < 0.01).

Conclusion:Surgical bootcamps serve as a framework for documenting achievement and offering remediation of CEPAER.  Further course development can ensure all entrustable professional activities are included in the curriculum.

 

40.10 Evaluation of a Surgery-Based Adjunct Course for Medical Students Entering Surgical Residencies

Posted on December 22, 2014

C. A. Green1, S. M. Wyles1, E. H. Kim1, P. S. O’Sullivan1, H. Chern1  1University Of California – San Francisco,Department Of Surgery,San Francisco, CA, USA

Introduction: Educators have developed preparatory courses for senior medical students (SMS) entering surgery aiming to improve the transition from medical school to residency. We chose to design a novel curriculum that can be embedded in a capstone course to enhance student’s readiness for surgical internship. The course emphasizes major intern competencies, ward management and technical skills, through interactive simulation and practice activities. This study aims to assess the feasibility and outcomes of this course.

Methods: A surgical curriculum was designed and executed based on competencies highlighted in our surgical intern milestones. Students participated in 8 (3-hour) sessions held over four weeks as an adjunct to the well-established intern preparatory course at our institution. Course activities involved interactive simulation cases and mock page encounters to emphasize post-operative patient care and management of the critically ill. Additional sessions included technical skills exercises reinforced with home video assignments. Students rated confidence on 13 management skills using a five-point Likert scale (5=high confidence). Confidence levels were then averaged to give an overall score. Faculty graded students’ technical performance using a global grading scale (1 to 10) for 5 different suturing exercises. Students completed all measures both on the first and last day of the course. Comparisons between pre- and post-course data were made using t-tests (a=0.05).

Results: 11 students entering 4 different types of surgical residencies enrolled in the 2014 course. Assessment of overall confidence in patient management improved from 2.41 to 3.89 (SD 0.49, 0.35; P<0.05). Additionally, student scores on fundamental suturing exercises significantly increased in all 5 tasks (P<0.05) (Figure 1).

Conclusion: We developed and incorporated a surgical component to the existing preparatory course at our institution. Our results illustrate the feasibility of an adjunctive specialty-specific curriculum for SMS entering surgical residencies. Students demonstrated increased confidence in ward management skills and increased technical scores in all measured exercises. The technical improvement is noteworthy because only 3 of the sessions were dedicated to these skills. The significant progress may be due to the additional implementation of the home video component. Investigation into subsequent performance benefits is warranted. This course serves as a specialty-specific model for schools with existing preparatory courses. Our described curriculum allows for consolidation efforts to maximize resources while still highlighting specific components to heighten participants’ readiness for surgical residency.

41.01 Protein Kinase A Inhibition Protects Against Experimental Necrotizing Enterocolitis.

Posted on December 22, 2014

B. J. Blackwood1,3, D. Wood2, C. Yuan2, J. Nicolas2, C. J. Hunter1,2  1Ann & Robert H. Children’s Hospital Of Chicago,Pediatric Surgery,Chicago, IL, USA 2Northwestern University,Surgery,Chicago, IL, USA 3Rush University Medical Center,Chicago, IL, USA

Introduction:  Necrotizing Enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants. Cronobacter sakazakii (CS) has been associated with out breaks of infant NEC.  Protein kinase A is a common mediator implicated in cell survival and apoptotic pathways.  We hypothesized that protein kinase A (PKA) inhibition would be protective against experimental NEC.

Methods:  Rat intestinal epithelial cells (IEC-6) were grown to confluence and exposed to CS. PKA inhibitors (KT-5720 & SC-3010) were added at doses of 0.1uM, 1uM and 10uM prior to CS infection. IEC-6 cell apoptosis was assayed by western blot of Caspase 3, and by TUNEL staining using the ApoTag red kit. PKA siRNA knocked down PKA in IEC-6 cells and apoptosis was assayed.  Rat pups were orally administered a PKA inhibitor (KT-5720), prior to induction of experimental NEC with CS and hypoxia.  Mortality rates were measured. Intestinal segments were processed for histology, intestinal injury scoring and ApoTag staining, as well as for western blot analysis for caspase-3.  Differences were analyzed with ANOVA where appropriate

Results: PKA is present in IEC-6 and appears to be activated by infection with CS. The addition of a PKA inhibitor prior to IEC-6 infection with CS prevents CS-induced apoptosis (p<0.005).  Western Blot analysis revealed a five-fold reduction in expression of PKA in IEC-6 cells with PKA siRNA knockdown. Additionally, a four-fold reduction in Caspase 3 expression was seen in these same cells. Rat pups given the PKA inhibitor prior to induction of experimental NEC, has significantly lower mortality (FIgure 1) (p < 0.001), less intestinal injury (p< 0.001), and decreased intestinal apoptosis as compared with controls.

Conclusion: We conclude that PKA mediated signaling may play an important role in CS-induced intestinal epithelial apoptosis, and that PKA inhibition is protective against experimental NEC. The prospect of PKA inhibitors presents an interesting potential therapeutic line of investigation. 

 

41.02 Treatment of Necrotizing Enterocolitis with Enteral Intestinal Alkaline Phosphatase

Posted on December 22, 2014

B. Biesterveld1, N. Heinzerling2, R. Rentea2, S. Welak3,4, K. Fredrich2, D. Gourlay2,5  1Medical College Of Wisconsin,Milwaukee, WI, USA 2Medical College Of Wisconsin,Surgery,Milwaukee, WI, USA 3Medical College Of Wisconsin,Pediatrics,Milwaukee, WI, USA 4Children’s Hospital Of Wisconsin,Neonatology,Milwaukee, WI, USA 5Children’s Hospital Of Wisconsin,Pediatric Surgery,Milwaukee, WI, USA

Introduction:  Necrotizing enterocolitis (NEC) is the most common surgical emergency of the neonate. Previously, we demonstrated intestinal alkaline phosphatase (IAP) activity to be decreased in a neonatal rat model of NEC.  Furthermore, enteral IAP supplementation before the onset of NEC prevented NEC development, reduced intestinal inflammation and maintained gut barrier function. It is not known if IAP given after NEC onset can reverse the course of the disease. We hypothesized that enteral IAP given after induction of NEC would not be able to reverse intestinal injury.

Methods:  Sprague Dawley pups were delivered 1-day preterm followed by NEC induction with LPS added to formula and hypoxia exposure. All pups received NEC stressors on days 0 and 1. They were subsequently divided into 4 groups: continued NEC stressors (NEC), continued NEC stressors with enteral IAP (NEC+IAP), withdrawal of NEC stressors then formula fed (NEC then FF) or withdrawal of NEC stressors then formula fed with supplemental IAP (NEC then IAP) on days 2,3. Control pups were spontaneously delivered and dam-fed. All pups were then sacrificed on day 4. NEC severity was scored based on H&E stained terminal ileum sections, and AP activity was measured using a colorimetric assay. IAP and IL-6 expression were measured using RT-PCR.

Results: Intestinal AP activity in the NEC group was significantly decreased 0.18 U/mg compared to controls of 0.57 U/mg (p<0.001). Discontinuation of NEC stressors after 2 days (NEC then FF) was associated with increased AP activity to 0.36 U/mg (p<0.01 vs. NEC). IAP supplementation in matched groups, NEC+IAP and NEC then IAP, did not impact AP activity. IAP mRNA expression followed a similar trend as activity, with significantly decreased IAP expression in NEC which significantly increased with withdrawal of NEC stressors on day 2. Similarly, the NEC group had significantly worse mean injury score (2.25 vs. 0.67 in control (p<0.01).  Discontinuation of NEC stressors on day 2 resulted in improved intestinal injury scores to 1.14 compared to continued NEC stressors (p<0.01).  While, IAP supplementation (NEC then IAP) significantly decreased IL-6 expression two-fold compared to NEC (p<0.05), it did not decrease the intestinal injury when compared to matched groups in NEC vs. NEC+IAP (p=0.50) and NEC then FF vs. NEC then IAP (p=0.54).

Conclusion: This is the first work to demonstrate that the current clinical treatment, to remove the source of NEC, improves intestinal damage and this is associated with a return of IAP expression and activity. When used as a rescue treatment after NEC onset, IAP decreased intestinal inflammation though did not impact the severity of histologic injury. Given the often rapid progression of NEC, and our previous work demonstrating the ability of early IAP supplementation to prevent NEC development, this data supports the use of IAP as a preventive therapy given to all those identified as at risk early in life.

 

41.03 Nanocarrier-modified Mesenchymal Stem Cells Improve Hyperglycemia in Diabetic Mice

Posted on December 22, 2014

D. Horkan1, B. Wang1, Y. Li1, Z. Liu1, O. Velazquez1  1University Of Miami,Division Of Vascular And Endovascular Surgery, Department Of Surgery, Leonard M. Miller School Of Medicine,Miami, FL, USA

Introduction:  Diabetes mellitus (diabetes) is the most common metabolic disorder in the United States affecting an estimated 29 million Americans. In diabetes, pancreatic islet injury results in disordered glucose metabolism leading to ischemic heart disease, peripheral arterial disease, and renal damage which are responsible for morbidity and mortality. Current therapies show promise for cure, but are limited due to emphasis on replacement of or compensation for the dysfunctional pancreatic islet rather than repair of damaged islet tissue. Mesenchymal stem cells (MSC) carry high therapeutic potential for tissue regeneration and are ideal therapeutic tools for repairing damaged pancreatic islet. Herein, we tested the effect on hyperglycemia of a novel stem cells-based therapy using nanocarrier-modified MSC for targeted repair of injured pancreatic islet in a mouse model of type 1 diabetes.

Methods:  Bone marrow cells were harvested from C57BL6 mice and cultured in MesenCult™ medium to selectively enrich MSC. Cultured MSC were modified with a cell membrane-bound nanocarrier composed of poly(amidoamine) (PAMAM) dendrimer coupled with either a specific adhesion molecule or albumin as control. These nanocarrier–modified MSC selectively associate with counterpart adhesion molecules highly or selectively expressed on the inflamed islet endothelium of recipient diabetic mice, which are streptozocin-induced C57BL6. Low-dose intraperitoneal injection of streptozocin induces type 1 diabetes with concurrent islet inflammation. 1 x 10^6 nanocarrier (PAMAM-adhesion molecule)- versus control nanocarrier (PAMAM-albumin)-modified MSC were infused into recipient diabetic mice via the tail vein (N=5/group) at two and five weeks post-streptozocin induction. For each group, blood glucose levels (BG) were measured at baseline and weekly thereafter.

Results: At baseline, mean BG values for control and experimental groups were euglycemic with no statistically significant difference (98 mg/dL vs 101, ρ = 0.35). One week post-streptozocin induction, mean BG for both groups showed hyperglycemia with no statistical difference (456 vs 444, ρ = 0.36). At seven weeks post-streptozocin induction, control group mice showed statistically significant higher mean BG compared to experiment group (548 vs 362, ρ = 0.02).

Conclusion: In our murine model of type 1 diabetes, systemic administration of nanocarrier-modified MSC showed significantly improved hyperglycemia compared to administration of control MSC. Our results revealed a promising therapeutic effect of nanocarrier-modified MSC on improving hyperglycemia, which is presumably achieved through targeted repair of inflamed/injured pancreatic islet. Notably, however, this therapy failed to normalize blood glucose levels after eight weeks of follow-up. It may be that administration of nanocarrier-modified MSC earlier in the inflammatory process could lead to repair of islet and normalization of glucose levels in diabetes.

41.04 Progenitor Cell Recruitment to Injured Tissue is Critically Regulated by Endothelial Cell SDF-1

Posted on December 22, 2014

Z. N. Maan1, D. Duscher1, A. J. Whittam1, G. G. Walmsley1, R. C. Rennert3, M. Januszyk1, M. S. Hu1, L. H. Fischer1, I. N. Vial2, N. Ho1, S. Khong1, E. R. Zielins1, A. J. Whitmore1, M. T. Longaker1, G. C. Gurtner1  1Stanford University,Surgery,Palo Alto, CA, USA 2University Of Pittsburg,Plastic Surgery,Pittsburgh, PA, USA 3University Of California – San Diego,Neurosurgery,San Diego, CA, USA

Introduction: An impaired neovascular response underlies the significant cardiovascular and wound healing complications seen in elderly and diabetic patients. Stromal-derived factor-1 (SDF-1), a cytokine primarily known for inflammatory cell recruitment, is also thought to play a major role in trafficking progenitor cells to ischemic tissue.  Recent studies have found that diabetics and the elderly are deficient in SDF-1, suggesting a possible mechanism for their impaired neovascularization and subsequent cardiovascular and wound complications. Utilizing newly developed murine models, we studied the effect of global (gKO) and endothelial cell-specific SDF-1 knockout (eKO) during neovascularization.

Methods: Humanized excisional wounds were created on the dorsum of gKO, eKO and wild type mice. An ischemic skin flap was created on the dorsum of eKO and WT mice. Wounds and flaps were photographed and assessed at regular intervals. Tissue was harvested for histology and qRT-PCR. The excisional wound model was repeated in eKO and WT mice parabiosed to GFP+ reporter mice and FACS and microfluidic single cell analysis was used to assess recruitment of circulating progenitor cells.

Results: The eKO and gKO groups demonstrated similarly impaired wound healing (*p=0.006). eKO wounds had reduced transcription, shown by qRT-PCR, and protein expression, on immunofluorescent staining, of SDF-1 (*p=0.002; *p=0.008), vascular endothelial growth factor (VEGF) (*p<0.05; *p<0.05) and fibroblast growth factor-2 (FGF-2) (*p<0.05; *p=0.006) with decreased vascular density (*p<0.05). eKO mice also had reduced ischemic flap survival (39% v 72%; *p=0.008) associated with decreased vascular density (*p=0.003). WT mice demonstrated increased recruitment of circulating progenitor cells (GFP+, Lin-) to wounds compared to eKO mice (*p<0.001). Single cell analysis identified a specific sub-population of progenitor cells absent in the wounds of eKO mice.

Conclusion: Endothelial cell SDF-1 (eSDF-1) plays a pivotal role in the vascular response, regulating the expression of cytokines responsible for neovascularization, recruiting a specific population of circulating progenitor cells and subsequently increasing vascular density in ischemic tissue.

 

41.05 Subpopulation Enrichment Enhances the Potential of Cell-Based Therapy for Diabetic Wounds

Posted on December 22, 2014

D. Duscher1, R. C. Rennert1, M. Januszyk1, Z. N. Maan1, A. J. Whittam1, M. Rodrigues1, M. W. Findlay1, M. S. Hu1, G. G. Walmsley1, R. Kosaraju1, S. Kong1, D. Atashroo1, G. C. Gurtner1  1Stanford University,Division of Plastic Surgery,Stanford, CA, USA

Introduction:
Mesenchymal stromal cells derived from adipose tissue (ASCs) have been used clinically to promote wound healing. However, the regenerative capacity of ASCs is impaired in diabetic and aged populations, potentially limiting the efficacy of autologous cell based therapies in these patients. Exploring cell enrichment strategies to overcome this deficiency, we employed microfluidic single cell transcriptional analysis paired with a novel bioinformatics approach to identify and isolate a subpopulation of ASCs with increased regenerative potential.

Methods:
Primary ASCs were isolated from human and murine healthy, diabetic and aged adipose tissue, and microfluidic-based single cell transcriptional analysis was employed to simultaneously characterize the expression of 96 angiogenic, stemness, differentiation and pre-selected surface antigen genes. A novel bioinformatic clustering analysis was used to identify ASC subpopulations based on transcriptional profiles, and a putatively pro-vasculogenic subpopulation was prospectively isolated using fluorescence assisted cell sorting (FACS) for assessment of enhanced functional capacity in vitro and in vivo.

Results:
Single cell transcriptional analysis revealed a subpopulation of human and murine ASCs characterized by an elevated expression of multiple stemness-associated and pro-angiogenic genes, which was significantly depleted in ASCs isolated from diabetic and aged samples. Prospective subpopulation isolation using correlative surface markers resulted in prolonged retention of progenitor associated surface antigens, increased cell survival, proliferative capacity and clonogenicity, and upregulation of angiogenic cytokines when compared to negatively selected and parent populations. When applied to an in vivo diabetic wound healing model, this newly defined ASC subpopulation significantly improved healing compared to negatively selected and parent populations, and critically restored normal healing kinetics to diabetic wounds. 

Conclusion:
Functionally distinct ASC subpopulations can be transcriptionally identified and linked to surface marker expression for prospective isolation and verification of predictive functionality. Demonstrating the validity of this approach, enrichment of a putatively pro-angiogenic ASC subpopulation was found to enhance the regenerative potential of ASC-based therapies in diabetic wounds. Moreover, the depletion of this same functional subset from diabetic and aged ASCs suggests a previously unreported mechanism for the cell dysfunction observed in these settings. 
 

41.06 Fibroblast-Specific STAT3 Signaling of IL-10 Mediates Regenerative Wound Healing

Posted on December 22, 2014

R. Ranjan1, S. Balaji1, S. S. Bhattacharya1, C. M. Moles1, N. Hann1, A. F. Shaaban1, P. Bollyky3, T. M. Crombleholme2, S. G. Keswani1  1Cincinnati Children’s Hospital Medical Center,Laboratory Of Regenerative Wound Healing, Division Of Pediatric, General And Thoracic Surgery,Cincinnati, OH, USA 2Children’s Hospital Colorado,Aurora, CO, USA 3Stanford University,Infectious Diseases In The Department Of Medicine,Palo Alto, CA, USA

Introduction: We have previously reported that IL-10 overexpression results in fetal-type regenerative repair in postnatal wounds via a STAT3 dependent mechanism. It is unclear which cellular compartment of the wound is responsible for IL-10’s effects. The fibroblast is the main cellular mediator of scarring and has a significant role in the fetal regenerative phenotype. Taken together, we hypothesize that IL-10’s regenerative effects are dependent on fibroblast-specific STAT3 signaling.

Methods: We developed inducible STAT3 knockdown models which were Fibroblast specific (Col1a2-Cre), Keratinocyte specific (Krt14-Cre) and Skin specific (UBC-Cre). IL-10 was overexpressed (lentiviral-CMV-IL-10;106 T.U.) and 4 mm wounds were created and evaluated at 28 days in all models. In a gain of function experiment, we used a fibroblast transplant model in which the fibroblast is the only cell in the wound capable of responding to IL-10. Syngeneic fibroblasts expressing IL-10 or GFP were transplanted into the wounds of skin specific STAT3 knockout mice and analyzed at 28 days. A quantifiable six-parameter histologic scar scoring scale was developed to evaluate scar formation, with uninjured skin benchmarked to zero. The mean and standard deviation are calculated based on which a 95% confidence interval is reported, p values by ANOVA/ t-test.

Results: In normal controls, IL-10 overexpression resulted in a significant improvement in scar formation compared to the PBS treatment (p<0.0001). Skin-specific STAT3 knockdown resulted in loss of IL-10 effect on scar attenuation to a level that is similar in PBS scar (p=ns), suggesting that IL-10 effects are mediated via STAT3 signaling. Fibroblast-specific STAT3 knockout similarly abrogates IL-10 effects (p=ns), suggesting that fibroblasts are a primary mediator of IL-10 effects. Keratinocyte-specific STAT3 knockout results in a partial attenuation of IL-10 effects (p<.01), suggesting IL-10 effects are in part mediated by keratinocytes. Syngeneic transplant of fibroblasts expressing GFP resulted in normal scarring (p=ns), but transplant of fibroblasts overexpressing IL-10 resulted in a significant improvement in scar reduction (p<0.01), albeit less than the effect of lenti-il-10 treatment.

Conclusion: IL-10 effects on attenuating scar formation are primarily mediated via STAT3 signaling in dermal fibroblasts. However, the partial loss of effect on dermal appendages suggests potential epidermal–dermal interactions may be important. Understanding these fundamental mechanisms will permit the development of novel clinically translatable regenerative therapies.

 

41.07 Generation of human autologous transgene-free cardiomyocytes in hypoplastic left heart syndrome

Posted on December 22, 2014

S. M. Kunisaki1, G. Jiang1, J. Di Bernardo1, T. J. Herron1, K. S. O’Shea1  1University Of Michigan,Ann Arbor, MI, USA

Introduction:  Hypoplastic left heart syndrome (HLHS) is one of the most devastating congenital heart anomalies in children. The local delivery of replacement cells has been investigated as a promising adjunctive therapy aimed at enhancing cardiac function in these infants. The purpose of this study was to generate transgene-free cardiomyocytes derived from HLHS neonates as a prelude to subsequent autologous applications.

Methods: With IRB approval, neonatal dermal fibroblasts were harvested from HLHS (n=1) and control (n=2) foreskin samples prior to cellular reprogramming into induced pluripotent stem cells (iPSCs) using non-integrating Sendai RNA viral vectors expressing OCT4, SOX2, cMYC, and KLF4. The resultant iPSCs were then differentiated into cardiomyocytes by a modified Matrigel sandwich technique and characterized in multiple assays, including confocal immunofluorescence, quantitative gene expression, and electrophysiological testing.

Results: iPSCs were successfully generated from both HLHS and control dermal fibroblasts based on morphological characteristics and alkaline phosphatase staining. The pluripotency of HLHS iPSCs was confirmed by the expression of NANOG, OCT4, SOX2, SSEA3, TRA-1-81, and TERT, and by three germ layer lineage differentiation of embryoid bodies. Two weeks after induced differentiation, beating cells were identified and expressed MYH7, MF20, actinin, and MLC2v after six weeks in culture. Optical mapping of calcium transients and transmembrane voltage studies were consistent with that of cardiomyocytes (Graphic). There were no major differences noted between cardiomyocytes derived from HLHS and controls.

Conclusion: Beating human cardiomyocytes can be generated in a minimally invasive fashion in HLHS. This study supports the feasibility of autologous transgene-free cardiomyocyte-based therapies in the management of severe congenital heart disease. 

41.08 Requirement for Actin Capping Protein CAPZB in Cleft Pathogenesis and Lower Jaw Extension

Posted on December 22, 2014

K. Mukherjee1,2, M. J. Grimaldi1, M. Talkowski2,4, J. F. Gusella2,4, R. Maas2,3, C. C. Morton2,5, E. C. Liao1,2  1Massachusetts General Hospital,Center For Regenerative Medicine,Boston, MA, USA 2Harvard School Of Medicine,Brookline, MA, USA 3Brigham And Women’s Hospital,Division Of Genetics,Boston, MA, USA 4Massachusetts General Hospital,Center For Human Genetic Research,Boston, MA, USA 5Brigham And Women’s Hospital,Department Of Pathology,Boston, MA, USA

Introduction: Orofacial clefts are among the most common congenital anomalies. The genetic basis for cleft palate and other craniofacial malformations is being elucidated. The Developmental Genome Anatomy project (DGAP) has developed whole genome sequencing strategies to identify genes contributing to such human congenital anomalies. The isolated disruption of CAPZB was identified in a 6-month old DGAP patient presenting cleft palate, micrognathia and hypotonia. We exploit the zebrafish model to determine the function of capzb and to understand the role of actin dynamics in craniofacial development and cleft pathogenesis. 

Methods: The Meckel’s cartilage and ethmoid plate are analogous to the mammalian mandible and primary palate respectively, making zebrafish an ideal model to study the genetic and developmental basis of palate and lower jaw morphogenesis. The spatiotemporal gene expression of capzb is determined by whole mount in situ hybridization (WISH) during early embryogenesis. Furthermore, craniofacial cartilaginous structures and muscles are examined in the capzb mutant identified from an insertional mutagenesis screen.

Results: WISH analysis shows that capzb is 
ubiquitously expressed, demonstrating its potential requirement in the
 function of many tissue types. Preliminary analysis of the
 capzb mutant show that the lower jaw elements are smaller and 
retrusive and the palate is only partially fused, leading to a cleft. The actin cytoskeleton is disorganized without capzb, leading to loss of cell morphology in the palate chondrocytes. The capzb mutants also show highly disorganized myofibrils leading to atrophied muscles. 

Conclusion: We successfully modeled the phenotypes observed in the DGAP patient, in the zebrafish. We show that the capzb mutants exhibit micrognathia, cleft palate and atrophied muscles. We identify CAPZB to be important in craniofacial and muscle morphogenesis, disruption of which is pathologic for both palate and muscle development. Preliminary results from characterization of the capzb
 mutant suggest that it plays a role in palate
fusion and lower jaw extension, and affects tissue types where actin organization is critical to cell morphology and higher order organ morphogenesis. We show that capzb is maternally transcribed and hence the mutants survive through embryogenesis even with loss of a critical gene involved in basic actin dynamics. Experiments are under way
to delineate the mechanisms of capzb function in craniofacial morphogenesis, regulating fundamental cellular mechanisms where actin cytoskeleton and cell signaling pathways intersect. This study illustrates how clinically based studies can uncover fundamental mechanisms that govern cell biology and tissue morphogenesis.

 

 

41.09 Autophagy pathway mediates environmental stress in orofacial cleft pathogenesis.

Posted on December 22, 2014

L. J. Rochard1, K. Mukherjee1, T. J. Hoyos1, E. C. Liao1  1Massachusetts General Hospital,Center For Regenerative Medicine,Boston, MA, USA

Introduction: Orofacial clefts, such as cleft lip and palate (CL/P) are the most common congenital anomalies worldwide. The etiology of non-syndromic CL/P is complex, with interplay of genetic, epigenetic and environmental factors. We investigate naturally occurring human chromosomal aberrations resulting in orofacial clefts to identify the underlying genetic basis and elucidate the role of such genes in craniofacial development. This functional genomics approach identified ATG4C to be important in palate development.  ATG4C is a key enzyme that catalyzes the cellular recycling of autophagosome, organelles that are essential for cellular homeostasis and stress response.  Autophagy is required to respond to malnutrition and hypoxia states.  Environmental stresses such as hypoxia or smoke have been implicated in CL/P but how they interact with the genome during pregnancy to lead to the malformation is not known. Implication of autophagy in cleft pathogenesis is exciting, as it potentially elucidates how environmental stress potentiates cleft malformation.

Methods: We utilize the zebrafish model to investigate the role of autophagy in craniofacial development. Spatiotemporal gene expression analysis of atg4c was performed by wholemount RNA in situ hybridization (WISH). Morpholino-mediated gene knockdown was performed to assess gene function in vivo. Targeted mutagenesis of atg4c locus was achieved by CRISPR/Cas genome editing method. 

Results:Genetic analysis of a patient presenting chromosomal translocation identified breakpoint in the ATG4C gene, which encodes a cysteine protease involved in maturation and recycling of LC3, a key protein of the autophagic pathway. Genomic database (DECIPHER) analysis identified additional patients reported with CL/P. Morpholino mediated gene knockdown of atg4c in zebrafish phenocopied cleft palate.  CRISPR mediated targeted mutagenesis developed craniofacial anomalies in stress conditions, such as inhibition of mTOR pathway or induction of hypoxia.

Conclusion:The link between environmental stress and craniofacial malformations has been elusive; therefore identification of autophagy as a regulator of embryonic craniofacial development is exciting and leads to novel understanding of CL/P pathogenesis. Importantly, Autophagy is under intense investigation as a pathway important in carcinogenesis and bone homeostasis, and as such, many drugs regulating this pathway have been developed.  The zebrafish model affords the opportunity to test these drugs in small molecule screens to identify chemical modifiers that may augment cellular stress response and mitigate craniofacial malformation, to prevent CL/P before they form.

 

42.01 Heterogeneity in indirect pathway CD4 T cell alloresponses

Posted on December 22, 2014

J. M. Ali1, M. C. Negus1, E. M. Bolton1, K. Saeb Parsy1, J. A. Bradley1, G. J. Pettigrew1 1Department of Surgery, University of Cambridge

Introduction:
Uniquely alloantigen is recognised by two pathways: the direct and indirect. The indirect pathway is believed to be long-lived, and thought of as a single entity. Here we address how indirect responses against different alloantigens differ in their strength and longevity. 

Methods:
A murine model of cardiac transplantation was utilised [bm12.Kd.IE to C57BL\6]. Indirect CD4 T-cell allorecognition of donor MHC class I and II, and H-Y minor antigen was assessed by quantifying proliferation of adoptively transferred monoclonal T-cell receptor transgenic T-cells (TCR75, TEa and Mar respectively) at various time points. Antigen presentation by dendritic cells (DC) was assessed by selective depletion using diphtheria toxin; and B-cells, by administering depleting anti-CD20 monoclonal antibody. 

Result:
Indirect pathway responses were heterogeneous. Whereas the indirect response against class I alloantigen was long-lived and persistently strong, the class II indirect response was remarkably short-lived (decaying within two weeks), because it is dependent upon donor B-cells and DC’s as a source of class II alloantigen, and these are cleared rapidly by the recipient. The longevity of the class I indirect response reflected on-going antigen presentation, but notably B-cells played an increasingly important role, perhaps reflecting antigen-specific expansion. Finally, the indirect response against minor H-Y antigen was long-lived but weakened progressively. 

Conclusion:
Although thought of as a single entity, our results highlight that indirect allorecognition comprises a number of responses that vary in duration and strength according to target alloantigen. Targeting those responses that are long-lived may be particularly effective at preventing chronic rejection. 

38.07 National Trends in the Receipt of Post-Mastectomy Radiation Therapy

Posted on December 22, 2014

L. L. Frasier5, S. E. Holden5, T. R. Holden6, J. R. Schumacher5, G. Leverson5, B. M. Anderson8, C. C. Greenberg5, H. B. Neuman5,7  8University Of Wisconsin,Department Of Human Oncology,Madison, WI, USA 5University Of Wisconsin,Wisconsin Surgical Outcomes Research Program, Department Of Surgery,Madison, WI, USA 6University Of Wisconsin,Department Of Medicine,Madison, WI, USA 7University Of Wisconsin,Carbone Cancer Center,Madison, WI, USA

Introduction:  In the past decade, there is new evidence that patients receiving post-mastectomy radiation therapy (PMRT) experience reduced recurrence and an absolute survival benefit, strengthening consideration in patients with risk profiles for which PMRT has not previously been recommended. However, the actual impact of these data on practice has not been examined. We sought to investigate changes in rates of PMRT over time according to risk of recurrence.

Methods:  Female patients with stage I‑III breast cancer who underwent mastectomy from 2000-2011 were identified in the SEER database (n=62,442). Temporal trends in the proportion of patients receiving PMRT were investigated, grouping patients by tumor characteristics associated with prognosis (tumor ≤ vs. > 5 cm; 0, 1‑3, or 4 or more lymph nodes). Joinpoint regression fits a series of joined straight lines together to determine whether there is a statistically significant change in the slope of the line(s) at any given point. We used this to analyze trends of PRMT use over time. Results are further summarized as annual percentage change (APC), or the slope of the line segment. 

Results: The highest receipt of PMRT (initially 62%) was seen in patients at highest risk of recurrence, those with four or more positive lymph nodes (any tumor size) and patients with >5 cm tumors and 1-3 positive lymph nodes. For this group of patients, receipt of PMRT was increasing by 0.8% per year and stable over the study period (no change in slope was identified). PMRT receipt was lowest (initially 7.5%) for patients with tumors ≤5 cm and no positive lymph nodes, and increased by 2.6% per year (no change in slope). In contrast, the cohort of patients with tumors ≤5 cm and 1-3 positive lymph nodes, had a baseline receipt of PMRT of 26.9%, and did not change  from 2000- 2006, after which change of  slope was identified (p=0.0189). Thereafter, the APC increased to 9.0% for the remainder of the study period (2007-2011). 

Conclusion: Since 2000, the use of PMRT has slowly but steadily increased over time for breast cancer patients across risk strata. However, there was a significant acceleration in the increased uptake of PMRT for patients with tumors ≤5 cm and 1-3 positive lymph nodes after 2007, likely representing change in practice patterns related to a broadening of the indications for PMRT in response to new evidence of a survival advantage.  It will be important to monitor the magnitude of benefit from PMRT in current everyday practice to ensure the improvements in disease free survival and overall survival persist and that the benefits of this treatment outweigh the risks.

 

38.08 Adjuvant Chemotherapy in Stage III Colon Cancer Patients Remains Underutilized

Posted on December 22, 2014

A. Z. Becerra1, C. P. Probst1, C. T. Aquina1, B. Hensley1, M. G. Gonzalez1, K. Noyes1, J. R. Monson1, F. J. Flemming1  1University Of Rochester,Surgery,Rochester, NY, USA

 Introduction:
There is strong evidence supporting the efficacy of adjuvant chemotherapy for pathological stage III colon cancer patients. Therefore, understanding factors associated with receipt of chemotherapy is important in order to identify subpopulations that might be at risk of not receiving optimal care. This study explores differences in adherence to evidence-based adjuvant chemotherapy guidelines for pathological stage III colon cancer cases across hospitals and patient subgroups. In addition, the relationship between receipt of chemotherapy and 5-year survival was examined. 

Methods:
Stage III colon cancer patients were identified from the 2003 – 2011 National Cancer Data Base (NCDB). Bivariate analyses assessed factors associated with receipt of adjuvant chemotherapy. Factors achieving a p-value < 0.2 were included in multivariable analyses. Logistic regressions were used to estimate receipt of adjuvant chemotherapy across varying hospital characteristics including geographic location, cancer center type, and hospital volume. Patient factors included were age at diagnosis, year of diagnosis, sex, race/ethnicity, insurance type, household income, education, urban/rural classification, Charlson comorbidity scale, and tumor histology. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to estimate the association between receipt of chemotherapy and 5-year survival for patients diagnosed from 2003-2006. In addition, the population attributable risk of death was calculated to estimate the number of deaths per year that could be avoided had everyone in the sample received adjuvant chemotherapy.

Results:
There were 124,008 patients who met the inclusion criteria. Adjuvant chemotherapy was not administered to 34% of the sample. Of these, 66% did not have a reason as to why chemotherapy was not offered as part of the planned first course of therapy. The rates of adjuvant chemotherapy have shown little improvement over time (63 % in 2003 vs. 66% in 2011). Factors associated with lower odds of receiving adjuvant chemotherapy include no insurance, lower income, worse comorbidity status, and black race. The Kaplan-Meier curves (Figure 1) indicate that patients receiving chemotherapy have better survival (p <0.001). This effect persisted in the multivariable analysis, which estimated a 52% reduction in the hazard of death (HR = 0.48, 95% CI: 0.47-049) in patients who received chemotherapy as compared to those who did not. The population attributable risk is 21% which indicates that over 1,400 deaths per year could be avoided if all stage III patients received adjuvant chemotherapy. 

Conclusion:
There has been no meaningful improvement in receipt of chemotherapy in patients with stage III colon cancer. The fact that chemotherapy was not being considered or offered to over 20% of patients with node positive colon cancer suggests that there are significant process failures across many institutions and regions in the United States.

38.09 Quality of Online Information to Support Shared Decision Making in Breast Cancer Surgery

Posted on December 22, 2014

J. G. Bruce1, J. Tucholka3, H. B. Neuman1,2,3  2University Of Wisconsin,Carbone Cancer Center,Madison, WI, USA 3University Of Wisconsin,Wisconsin Surgical Outcomes Research Program, Department Of Surgery, School Of Medicine And Public Health,Madison, WI, USA 1University Of Wisconsin,School Of Medicine And Public Health,Madison, WI, USA

Introduction:  Decision-making for breast cancer surgery relies heavily on women’s preferences. To reach an informed decision, women require treatment information that is complete, is easily understandable, and encourages them to consider their values in the context of treatment options. Our objective was to assess the quality of online information available to support shared decision making for breast cancer surgery.

Methods:  Four breast cancer surgery-related queries were done on Google and Bing, and websites from the first two pages reviewed. Two investigators evaluated each website for content pertinent to breast cancer surgery using an investigator generated list. The DISCERN instrument was used to evaluate: 1) websites’ structural components that influenced publication reliability, 2) quality of information on treatment choices. Scores on this 16-item validated questionnaire were normalized to a 5-point scale, with scores of 4/5 considered “good”. Agreement between reviewers on overall website quality was assessed.

Results: 45 unique websites were identified and reviewed (kappa 0.80). Websites were general information or health-care portals (48%), .GOV sites (13%), non-profit foundations (18%), hospitals (18%), and Youtube.com (2%). Websites satisfied a median 5/9 (range 0-9) content questions, with 2.2% covering all topics. Commonly omitted topics included: most women being candidates for both breast conservation and mastectomy (67%), the potential for a 2nd surgery to obtain negative margins after breast conservation (60%), post-surgery recovery times (58%), and equivalent survival regardless of surgery (53%). Websites had a median DISCERN score of 2.9 (range 2.0-4.5). Websites achieved higher scores on structural criteria (median 3.57 [2.07-4.71]), with 24.4% rated as “good”. In contrast, scores on treatment choice questions were lower (2.56 [1.3-4.38]), with only 6.7% scoring “good”. Four websites (all non-profit foundations) rated highly on both (figure). However, reviewers perceived these websites to be challenging to navigate, with significant effort required to find key content.

Conclusion: Although numerous online sources of breast cancer information exist, most websites do a poor job providing women with essential information necessary to play active roles in treatment decision-making. Even highly ranked websites provided information in a manner which was difficult to navigate and did not facilitate easy comparison of treatment choices in the context of women’s values. Access to high quality online breast cancer information that is balanced and approachable for Internet users of all experience levels would improve the quality of care provided to breast cancer patients.

 

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