51.09 Severe Presentation in Surgically Treated Colorectal Cancer Patients with Psychiatric Disease

Posted on January 26, 2017

K. F. Angell1, V. P. Ho1, N. K. Schiltz2, A. P. Reimer3, E. Madigan3, S. R. Steele1, S. M. Koroukian2  1Case Western Reserve University School Of Medicine,Department Of Surgery,Cleveland, OH, USA 2Case Western Reserve University School Of Medicine,Department Of Epidemiology And Biostatistics,Cleveland, OH, USA 3Case Western Reserve University School Of Medicine,Frances Payne Bolton School Of Nursing,Cleveland, OH, USA

Introduction:
Underlying psychiatric conditions may affect outcomes of comorbid conditions due to confusion or inconsistencies in both diagnosis and treatment. We hypothesized that patients with psychiatric illness (PSYCH) would have evidence of advanced disease at presentation, as manifested by higher rates of colorectal resection performed in the presence of obstruction, perforation, or peritonitis (OPP-resection).

Methods:
Using data from the 2007-2011 National Inpatient Sample (NIS), we identified patients 65 years of age or older with a diagnosis of CRC undergoing colorectal resection.   In addition to somatic comorbid conditions flagged in the NIS, we used the Clinical Classification Software to identify patients with PSYCH, including schizophrenia, delirium/dementia, developmental disorders, alcohol/substance abuse, and other psychiatric conditions.  Our study outcome was OPP-resection.  In addition to descriptive analysis, we conducted multivariable logistic regression analysis to analyze the independent association between each of the PSYCH conditions and OPP-resection, after adjusting for patient demographics and somatic comorbidities. 

Results:
Our study population included 60,147 patients with CRC and undergoing colorectal cancer resection, of whom 17.2% were 85 years of age or older, 51.9% were women, and 8.9% had 5 or more comorbid conditions.   Nearly 17% presented with PSYCH.  The percent of patients undergoing OPP-resection was 15.1% in the study population, but significantly higher in patients psychiatric diagnosed with schizophrenia (18.9%), delirium/dementia (18.9%), and alcohol/substance abuse (19.6%).  Findings from the multivariable analysis showed that these associations were relatively modest and at borderline statistical significance.  The odds ratios and 95% Confidence Interval were 1.24 (1.00, 1.54), 1.13 (1.02, 1.24), and 1.21 (1.05, 1.40), respectively for the aforementioned PSYCH conditions. 

Conclusion:
Patients with PSYCH may have obstacles to receiving optimal care for CRC. Those with select PSYCH diagnoses had significantly higher rates of OPP-resection albeit to a relatively modest extent.   It is important to note, however, that our study could not account for CRC patients who did not undergo surgery and were referred directly to hospice upon presenting with obstruction, perforation, or peritonitis.  Additional evaluation is required to identify the association between PSYCH and related factors affecting the rates of emergency surgery in patients with CRC.
 

51.08 Racial Disparities in Surgical Care after Parathyroidectomy

Posted on January 26, 2017

S. Jang1, C. J. Balentine1, H. Chen1  1University Of Alabama at Birmingham,Department Of Surgery,Birmingham, Alabama, USA

Introduction: Racial disparities in health care and health outcomes have been well documented in most diseases, but there is limited data for hyperparathyroidism. Parathyroidectomy is the only curative therapy for hyperparathyroidism, but its cost and variation in use among different racial and ethnic groups are largely unexamined. The purpose of this study was to examine the association between race and ethnicity and the total hospital cost of parathyroidectomy.

Methods: This retrospective study included 899 consecutive cases in our institution between September 2011 and July 2016 coded as complete parathyroidectomy, parathyroidectomy or exploration of parathyroid, or other parathyroidectomy using ICD-9 and 10 procedure codes. We evaluated demographics, insurance type, and readmission rates. Total length of stay and cost were evaluated using the Mann-Whitney U and the Kruskal-Wallis non-parametric tests. Categorical variables were evaluated with chi-square.

Results: The study population was 66.4% Caucasian, 31.4% African American, 0.7% Hispanic, and 0.3% Asian. Median age was 60 years (range 13-93), 76% were female, and 83% were outpatients. Total hospital costs were greater for African American patients ($5,025.22 ± 6,535.38, P = 0.013) compared to Caucasian patients ($4,787.49 ± $2,241.50) but costs were similar to Hispanic and Asian patients. Compared to Caucasian patients, African American patients were more likely to experience hospital costs greater than $10,000 (6.7% vs 2.1%, P = 0.001). Mean length of stay was 0.99 ± 3.14 for African American patients and 1.33 ± 1.21 for Hispanic patients while it was 0.44 ± 1.28 for Caucasian patients (P <0.001). African American patients were also more likely than Caucasians to be admitted to the ICU (22.7% vs. 13.2%, P < 0.001) and more likely to be readmitted after discharge (4.6% vs. 1.2%, P = 0.001). Among African American patients, male Black patients had a more expensive total hospital cost (trending P = 0.072), higher incidence of cases that cost greater than $10,000 (P = 0.005), longer length of stay (P < 0.001), and higher incidence of ICU admission (P < 0.001) compared to female Black patients.

Conclusion: African American race was associated with higher hospital costs for parathyroidectomy compared to Caucasian patients. The increased cost could be explained in part by longer length of stays after the operation and higher incidence of admission to the ICU. More detailed research and efforts are needed to reduce racial disparity in the management of parathyroidectomy patients.

51.07 Racial Disparities in Length-of-Stay for African-Americans with Metastatic Colorectal Cancer

Posted on January 26, 2017

L. Goss1,2, A. Gullick1,2, M. Morris1,2, J. Richman1,2, G. Kennedy1,2, D. Chu1,2  1University Of Alabama at Birmingham,GI Surgery,Birmingham, Alabama, USA 2VA Birmingham HealthCare System,Surgery,Birmingham, AL, USA

Introduction:

Racial disparities in surgical outcomes such as length-of-stay (LOS) exist with African-Americans having worse outcomes compared to other racial/ethnic groups. Surgery for metastatic colorectal cancer (CRC) is associated with poor outcomes and it is unclear if racial disparities exist. We hypothesized that African-Americans undergoing surgery for stage IV CRC would have worse surgical outcomes including longer LOS compared to other racial/ethnic groups.

Methods:

We queried the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) colectomy procedure targeted cohort for all patients who underwent surgery for stage IV colorectal cancer and stratified patients by race. Our primary outcome was LOS and secondary outcomes include 30-day mortality, 30-day readmission, and post-operative complications. Chi-square and Wilcoxon Rank Sums tests were used to determine differences among categorical and continuous variables, respectively. Stepwise backwards linear regression was performed to identify risk factors for LOS.

Results:

Of the 28,283 patients who underwent colectomy for colorectal cancer, 1,798 (6.4%) had stage IV cancer. Of these stage IV patients, 1,502 (83.5%) were white, 225 (12.5%) were African-American, and 71 (3.9%) were Asian-American. Similarities were seen between races in sex (p=0.86), smoking status (p=0.37), and steroid use (p=0.47). African-Americans were more likely to be on medications for hypertension (53.3%, p=0.04), have diabetes (19.6%, 0.03), and have an open approach (75.1%, p=0.01). African-Americans had a significantly longer post-operative hospital length of stay (7 days) when compared to white patients (6 days, p<0.01). There were no differences in 30-day readmissions or 30-day mortality by race. African-Americans had the highest rates of post-operative complications when compared to white and Asian-Americans including: wound complications (10.7% vs. 8.8% and 7%, p=0.57), sepsis (9.3% vs. 8.6% and 8.5%, p=0.94), respiratory complications (8.9% vs. 5.2% and 4.2%,p=0.07), renal complications (2.2% vs. 1.3% and 1.4%, p=0.52), and urinary tract infection (4.4% vs. 3.5% and 2.8%, p=0.71) but these were not statistically significant. On adjustment for covariate differences, African-American patients still had the longest LOS compared to white patients (p<0.01, Figure 1).

Conclusion:
African-Americans have a significantly longer LOS after colectomy for stage IV CRC compared to other racial/ethnic groups, but no difference in 30-day mortality or readmissions. Higher complications rates were observed in African-Americans although not statistically significant. Further investigations are needed to better understand the mechanisms underlying these disparities.
 

51.06 Assessing Racial And Socio-economic Disparities In Bariatric Surgery: The Impact On Patient Outcomes?

Posted on January 26, 2017

V. Pandit1, A. Azim1, I. Ghaderi1, C. A. Galvani1  1University Of Arizona,Department Of Surgery,Tucson, AZ, USA

Introduction:
Differences in outcomes among patients undergoing general surgical intervention based on racial and socio-economic profile are well established. However; the impact of these differences among bariatric patients still remains unclear. The aim of this study was to evaluate the impact of racial and insurance status on patient outcomes undergoing bariatric surgery (BS).

Methods:
National estimates for BS procedures were abstracted from the National Inpatient Sample (NIS) database (2011). Patients undergoing BS (sleeve gastrectomy, gastric banding) were included. Patients were stratified based on race and insurance status. Outcome measures were: hospital length of stay (LOS), complications, and mortality. Regression analysis was performed after adjusting for age, gender, race, Charlson co-morbidity index (CCI), and type of procedure

Results:
A total of 3,305 patients undergoing BS were analyzed. The mean age was 47.19±13.8 years, 74.8% were females and the mean CCI was 2 [2-3]. 64.1% patients were white and 10.6% were Hispanics. 52.2% patients were private pay. Hispanics patients and non-Hispanic black patients were more likely to develop intra-hospital complications (p=0.031, p=0.043) and have longer hospital stay (p=0.026, p=0.037) compared to non-Hispanic and white patients respectively.  On assessing insurance status, patients with Medicare/Medicaid insurance were more likely to have in-hospital complications (p=0.029) compared to private payers. Self-pay patients had lower complication rate ((p=0.041) and length of stay (p=0.033) compared to private payers. On regression analysis, Hispanic (1.28 [1.05-1.45]), non-Hispanic black (1.35 [1.18-2.05]), and Medicare/Medicaid insurance status (1.89 [1.2-3.1]) were independent predictors for development of in-hospital complications. There was no difference in mortality based on racial or socio-economic profile

Conclusion:
Racial and socio-economic disparities are prevalent among patients undergoing bariatric surgery with worse outcomes among Hispanic, Non-Hispanic black, and patients insured with Medicare/Medicaid insurance. Further assessing the causes for these disparities may help improve outcomes among patients undergoing bariatric surgery.
 

51.05 Black Race and Lack of Insurance are Associated with Increased Risk of Urgent Resection for Colon Cancer

Posted on January 26, 2017

M. C. Turner1, Z. Sun1, M. L. Cox1, M. A. Adam1, B. F. Gilmore1, C. R. Mantyh1, J. Migaly1  1Duke University Medical Center,Department Of Surgery,Durham, NORTH CAROLINA, USA

Introduction: Emergent surgery for colon cancer is associated with poor short-term outcomes and worse long-term survival compared to elective resection. However, the socioeconomic factors predisposing patients towards emergent or urgent operations are not well defined. We aim to evaluate the impact of race and insurance coverage for patients undergoing urgent colon resection.

Methods: We performed a retrospective analysis of the 2006-2013 National Cancer Data Base (NCDB) for stage I-III colon adenocarcinomas. Differentiating the level of urgency of resection is difficult in retrospective studies. However, when the definitive resection and the diagnosis of cancer occur on the same day, the operation was likely non-elective. Patients with matching date of diagnosis and date of definitive operation were categorized as urgent surgery. We reviewed the oncologic outcomes of urgent compared to elective colon resection, while adjusting for patient, operation, tumor, and facility characteristics. We utilized multivariate regression to evaluate the socioeconomic factors of race and insurance coverage for patients requiring urgent resection. 

Results: Among the 244,094 patients identified following colon resection, 59,918 (24.5%) underwent urgent resection. Those undergoing urgent operations had higher rates of positive margins (OR 1.36, p<0.01), 30-day mortality (OR 1.80, p<0.01), and worse long-term survival (HR 1.27, p<0.01). Overall, black patients (OR 1.15, p<0.01), and uninsured patients (OR 1.54, p <0.01) were more likely to undergo urgent resection. When stratified by race, among white patients those who are uninsured (OR 1.54, p <0.01) or have government insurance (OR 1.04, p <0.01) were more likely to undergo urgent resections compared to those who were privately insured. Similarly, among black patients, those who are uninsured (OR 1.42, p <0.01) were more likely to undergo urgent resections. When stratified by insurance status, race impacts urgent operations for those with private insurance (OR 1.12, p<0.01) and government insurance (OR 1.17, p <0.01), but not those who are uninsured (OR 1.07, p=0.27). 

Conclusions: Urgent resection for colon adenocarcinoma has inferior oncologic outcomes than elective resection. Black race and a lack of insurance are associated with higher risk of urgent operation. Resources to mitigate this risk, such as screening colonoscopy, should be designated to these at-risk populations to improve equitable oncologic care.

51.04 Improved Surgical Outcomes and Disparities for Asian-Americans with Colorectal Cancer

Posted on January 26, 2017

K. C. Mulhern1, A. A. Gullick1, L. Goss1, J. Richman1, G. D. Kennedy1, H. Chen1, M. S. Morris1, D. I. Chu1  1University Of Alabama at Birmingham,Division Of Gastrointestinal Surgery,Birmingham, Alabama, USA

Introduction:  Racial disparities in surgical outcomes exist. Studies in gastric cancer and hepatocellular carcinoma have suggested that Asian-Americans may have improved outcomes; however, no studies have focused on outcomes in Asian-Americans undergoing colorectal surgery for colorectal cancer. We hypothesized that Asian-Americans with colorectal cancer would have improved surgical outcomes in mortality, post-operative complications (POCs), length-of-stay (LOS) and readmissions compared to other races.     

Methods:  We queried the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) cohort for all patients who underwent surgery for colorectal cancer and stratified patients by race. Primary outcome was 30-day mortality. Secondary outcomes included POCs, LOS and 30-day readmission. Unadjusted univariate and bivariate comparisons were made. Chi-square and Wilcoxon Rank Sums tests were used to determine differences among categorical and continuous variables, respectively. Stepwise backwards logistic regression analyses and incident rate ratio (IRR) calculations were performed to identify risk factors for disparate outcomes.

Results: Of the 28,283 patients who underwent surgery for colorectal cancer, racial groups were divided into white (84%), African-American (12%), or Asian-American (4%). Asian-Americans were more likely than other racial groups to be of normal weight (53%, p<0.001), not smoke (90%, p<0.001), and have a low ASA score of 1 or 2 (55%, p<0.001). Compared to other racial groups, Asian-Americans were found to have the shortest LOS (5 days, p<0.001) and lower POCs due to ileus (10.3%, p<0.001), respiratory complications (3.1%, p<0.01), and renal complications (0.9%, p<0.001). There were no differences in 30-day mortality (1.5%, p>0.05) or 30-day readmissions (9.3%, p>0.05) (Table 1). On multivariate analyses, Asian-American race remained independently associated with less post-operative ileus (odds ratio [OR] 0.8, 95%-confidence interval [CI] 0.66-0.98) and decreased LOS by 13% as compared to African-Americans (IRR 0.87, p<0.001) and 4% as compared to whites (IRR 0.96, p<0.001).

Conclusion: Asian-Americans undergoing surgery for colorectal cancer have shorter LOS and lower POCs such as ileus when compared to other racial groups. There were no differences in mortality or 30-day readmissions. The mechanism(s) underlying these disparities will require further study, but may be a result of patient, provider, and healthcare system differences.

51.03 Variations in Bariatric Surgery Outcomes by Socioeconomic Status Among African-American Patients

Posted on January 26, 2017

M. Pichardo1, G. Ortega2, L. Bacon1, I. Yi1, C. Emenari1, N. Changoor3, D. Tapscott1, D. Tran3, T. Fullum3  1Howard University College Of Medicine,Washington, DC, USA 2Howard University College Of Medicine,Outcomes Research Center, Department Of Surgery,Washington, DC, USA 3Howard University College Of Medicine,Howard University Hospital, Department Of Surgery,Washington, DC, USA

Introduction: Bariatric surgery plays a vital role in the management of refractory obesity and comorbidities. The relationship between socioeconomic status (SES) and bariatric surgery has not been well elucidated, specifically among minority populations. Our study aims to assess the relationship between bariatric surgery outcomes, insurance status and SES among African-American patients.

 

Methods: Conducted a retrospective chart review with a 12-months follow up. Included 256 African-American patients who underwent bariatric surgery at an urban, academic institution between 2008 and 2013. Data collected included preoperative risk factors, BMI, procedure type, excess weight loss and resolution of comorbidities. Median Household Income (MHI), obtained from census-tract level neighborhood SES data, was a proxy for patients’ SES and categorized into 3 groups: group 1 (>$101,578), group 2 ($62,435 to $101,577), and group 3 ($38,515 to $62,434). No patient had an MHI below $38,515. Insurance status at time of surgery was defined as public or private insurance. Outcomes of interest included percent excess weight loss (%EWL) and resolution of comorbidities (hypertension, diabetes, dyslipidemia, obstructive sleep apnea (OSA)). Chi-square and students’ T tests were used to assess the relationship between our outcomes of interest, insurance status, and MHI.

 

Results: The mean pre-operative BMI was 48.0 kg/m2. A majority of patients had private insurance (90%) and underwent LRYGB (82%). Forty-nine percent of the sample lived in neighborhoods with an MHI of $62,435 – $101,577 (group 2). Group 1 patients had a lower proportion of diabetes remission compared to group 2 and 3 patients (p=0.016). No differences in resolution of hypertension, diabetes, and dyslipidemia were observed by MHI. A greater proportion of patients with private insurance relative to public insurance experienced OSA remission (p=0.021). Remission of other comorbidities did not significantly differ in the two insurance populations. The highest %EWL was observed among patients residing in areas with MHI of $101,578 or more (p=0.0096; group 1). No difference was observed in %EWL among patients with private vs public insurance.

 

Conclusions: Our findings reveal differences in SES and insurance status in bariatric surgery outcomes among an African-American population. Patients with private insurance experienced improved OSA outcomes relative to patients with public insurance. Patients in higher MHI neighborhoods experienced greater %EWL than those in lower income areas. However, lower and middle MHI neighborhood patients had better resolution of diabetes compared to patients living in the highest income areas. Further research is warranted to fully understand the effect of SES. Moreover, healthcare providers and policy makers should consider means of mitigating the effects of SES and insurance status among minority and low-income populations that can benefit from bariatric surgery.

51.02 Disparities in Thyroidectomy Outcomes at a Public and Private Hospital: Leveling the Playing Field

Posted on January 26, 2017

E. A. Alore1, S. Molavi1, C. J. Balentine2,3, J. W. Suliburk1  1Baylor College Of Medicine,Department Of Surgery,Houston, TX, USA 2University Of Alabama at Birmingham,Department Of Surgery,Birmingham, Alabama, USA 3University Of Alabama at Birmingham,Institute For Cancer Outcomes And Survivorship,Birmingham, Alabama, USA

Introduction:
Surgical outcomes for underserved patients facing social and economic disparities are frequently suboptimal. Our institution developed a multidisciplinary endocrine surgical team with carefully implemented postoperative care pathways to aid in the care of disadvantaged patients at our county safety net hospital. The purpose of this study is to compare surgical outcomes after thyroidectomy at our public hospital to outcomes at the private hospital in our institution. We hypothesized that our multidisciplinary patient-centered approach would largely eliminate disparities in postoperative outcomes.

Methods:
We performed a retrospective cohort study of 512 patients undergoing partial or total thyroidectomy at a private teaching hospital and a public safety net hospital within the same academic institution over 77 months from 1/2010 to 5/2016. The cases were performed by the same clinical team including surgery, endocrinology, anesthesiology and pathology. Temporary nerve injury was defined as injury that resolved within 6 months, temporary hypocalcemia was defined as immediate postoperative PTH <10, permanent nerve injury and hypocalcemia were defined as those which persisted >6 months post operatively.

Results:
A total of 358 patients from the public hospital and 154 patients from the private hospital were studied. 91% of patients at the public hospital were from racial/ethnic minorities compared with 42% of private hospital patients (p<0.001). 26% of patients at the public hospital were insured versus 100% at the private hospital (p<0.001). There were no significant differences in age, gender, cancer stage, or size of the thyroid gland. Rates of temporary nerve injury, permanent nerve injury, permanent hypoparathyroidism, postoperative hematoma or ER visits did not differ between groups (Table 1). Rates of temporary hypocalcemia at the public hospital (34.4%) were higher than at the private hospital (17.5%, p=0.001). We performed additional analyses stratified by type of insurance again finding rates of nerve injury, permanent hypoparathyroidism, postoperative hematoma or ER visits did not differ by type of insurance, but temporary hypocalcemia was more common in patients without insurance (38.5% vs 19.8%, p<0.001, Table 1).

Conclusion:
A dedicated endocrine surgery team was able to deliver excellent outcomes for patients lacking insurance and being treated at a public safety net hospital. Our findings suggest that social and economic disadvantages can be largely overcome for endocrine surgery patients with a combination of dedicated surgical care, multidisciplinary team coordination and patient-centered care pathways.
 

51.01 Spatial analysis of surgery service areas in Virginia

Posted on January 26, 2017

A. Diaz1, A. B. Haynes2,3  1Virginia Commonwealth University,Department Of Surgery,Richmond, VA, USA 2Massachusetts General Hospital,Department of Surgery,Boston, MA, USA 3Ariadne Labs,Boston, MA, USA

Introduction:  Hospital service areas(HSA) were created in the 1990s to help identify local health care markets. Based on these HSAs, health professional shortage areas(HPSA) were developed to identify populations without access to primary care. No such metric exists for surgery. Furthermore, recent policy changes leading to financial constraints and closure of rural and critical access hospitals (CAH) have obscured local surgical care markets. HSAs have not been updated to reflect recent closures and changing markets. We propose an alternative method of defining surgical markets based on travel time.

Methods:  We used publicly available datasets from Census.gov, Virginia Health Information, and the Virginia Geographic Information Network. We tabulated general surgeons, hospitals, and inpatient general surgery procedures per HSAs in Virginia using ESRI’s ArcGIS 10.3. Next, using the Network Analyst extension we created a network dataset of all roads with direction and speed limits in Virginia. We solved for the service area for acute care and critical access hospitals for various travel times.  Service areas were then overlaid on the 2010 census population block file and the total population within each respective service area was tabulated. 

Results: According to the 2010 census there were 8,001,024 people living in Virginia. There are 73 acute care hospitals and 7 CAHs. Of the 7 CAHs 3 do not perform any general surgery procedures and one performed only 2 procedures in 2014. These hospitals were excluded from the analysis.  700 physicians in the Virginia physician masterfile self identified as general surgeons. 9 of 23 HSAs were found to have fewer than 6 general surgeons per 100k residents; 1 of the 9 had fewer than 3 general surgeons per 100k residents.  Hospitals per 100k residents ranged from 0.39 to 3.71 per HSA and inpatient general surgeries ranged from 58.22 to 923.71 per 100k residents. Based on the service area analysis, we found that 595,070 residents lived further than 30 minutes from any hospital providing general surgical services. When modeled for closure of critical access hospitals an additional 69,234 residents would have to drive 30 minutes or more to the next nearest hospital. 

Conclusion: HPSAs based on HSAs have proven to be effective for primary care. Surgical service areas have been more elusive due to the added complexity of requiring a facility and staff to perform surgery. Furthermore, time may be of the essence in general surgery where an uncomplicated appendicitis or diverticulitis can become complicated in a matter of minutes to hours. A more accurate surgical service area might be reflected in metrics that take travel time into account. 

 

 

 

48.18 Postoperative Complications Associated With Parathyroid Autotransplantation After Thyroidectomy

Posted on January 26, 2017

Z. F. Khan1, G. A. Rubio1, A. R. Marcadis1, T. M. Vaghaiwalla1, J. C. Farra1, J. I. Lew1  1University Of Miami Miller School Of Medicine,Division Of Endocrine Surgery, DeWitt Daughtry Family Department Of Surgery,Miami, FL, USA

Introduction: Permanent hypoparathyroidism is a well-recognized complication of total thyroidectomy that may acutely manifest postoperatively with muscle spasms/tetany, paresthesias, and seizures. An established procedure, parathyroid autotransplantation (PAT) can successfully prevent permanent hypoparathyroidism due to inadvertently resected or devascularized parathyroid tissue. This study examines the independent patient characteristics and postoperative complications associated with those undergoing PAT after total thyroidectomy.

Methods: A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample (NIS) database from 2006-2011 to identify surgical patients hospitalized for total thyroidectomy that did or did not undergo PAT. Characteristics including co-morbidities and postoperative complications were measured. Univariate and logistical regression analyses were conducted to identify characteristics that were independently associated with patients that underwent PAT. Data were analyzed using two-tailed Chi-square and t-tests.

Results:Of 219,584 admitted patients who had total thyroidectomy, 14,521 (6.7%) also underwent PAT. Patients in the PAT group had fewer comorbidities including DM, HTN, CHF, chronic lung disease (12.5% vs 15.1%, 37.1% vs 39.9%, 1.5% vs 2.1%, 11% vs 12%, respectively,  p<0.01) and fewer cardiac complications including stroke and MI (0% vs 0.2% and 0.1% vs 0.2% , respectively, p<0.01). However, the autotransplanted group had higher rates of renal failure (2.7% vs 2.1%, p<0.01) and thyroid malignancy (55.4% vs 43.1%, p<0.01) compared to those not autotransplanted. The PAT group also had higher incidence of wound complications including SSI and seroma (2.6% vs 2.1%; 0.2% vs 0.1%; 0.2% vs 0.1%, p<0.01, respectively), unilateral vocal cord paralysis (2.4% vs 1.6%, p<0.01), substernal thyroidectomy (8.7% vs 7.5%, p<0.01) and in-hospital death (1.6% vs 0.3%, p<0.01). Immediate hypoparathyroidism (3.2% vs 1.3%, p<0.01), hypocalcemia (15% vs 8.6%, p<0.01), and tetany (0.3% vs 0.1%, p<0.01) were all associated with PAT patients as well. On multivariate analysis, renal failure (2.246 OR; 95% CI 1.448-3.485), and elective procedures (OR 1.744; 95% CI 1.422-2.129) were associated with increased odds of undergoing PAT during hospitalization for total thyroidectomy.

Conclusion:Although a known preventative measure for permanent hypoparathyroidism, PAT is associated with higher rates of postoperative complications. Patients with fewer comorbidities who undergo PAT experience higher rates of wound complications, hypoparathyroidism, hypocalcemia and tetany. Acute severity of postoperative hypoparathyroidism may further contribute to higher rate of in-hospital death in these PAT patients. PAT should not be routinely performed and utilized only in select patients with suspected compromised parathyroid function after total thyroidectomy

 

48.17 Subcutaneous Granular Cell Tumor: Analysis of 19 Cases Treated at a Dedicated Cancer Center

Posted on January 26, 2017

A. S. Moten3, S. Movva2, M. Von Mehren2, N. F. Esnaola1, S. Reddy1, J. M. Farma1  1Fox Chase Cancer Center,Department Of Surgery,Philadelphia, PA, USA 2Fox Chase Cancer Center,Department Of Hematology/Oncology,Philadelphia, PA, USA 3Temple University Hospital,Department Of Surgery,Philadelphia, PA, USA

Introduction:  Granular cell tumors (GCT) are rare lesions that can occur in almost any location in the body, and there have been no large-scale studies regarding GCT located in the subcutaneous tissue.   The aim of this study was to define patient characteristics, treatment patterns and outcomes of patients with subcutaneous GCT.

Methods:  A retrospective chart review was performed of patients with subcutaneous GCT treated at a dedicated cancer center.  Descriptive statistics were obtained, bivariate and multivariate regression performed, and survival rates calculated using Stata software.  

Results: A total of 19 patients were treated for subcutaneous GCT at our institution between 1992 and 2015, 79% female and 63.2% white.  Mean age was 48.2 years.  Most (68.4%) had comorbidities, and some (31.6%) had a history of cancer.  Mean tumor size was 2.37cm.   Most patients underwent primary excision of their tumors without undergoing prior biopsy (73.7%).  Men were more likely to undergo re-excision for positive margins than women (75.0% versus 13.3%, respectively, p-value 0.01).   No patient received adjuvant therapy.  Three patients (15.8%) had multifocal tumors, and they were significantly more likely to experience recurrence than patients with solitary tumors (33.3% versus 6.25%, respectively, p-value 0.02).  Patients with multifocal tumors were also more likely to undergo repeat surgery (33.0% versus 0%, respectively, p-value 0.02).  A total of 2 patients (10.5%) experienced recurrence, with a median time to recurrence of 23.5 months.  Overall cancer-specific 5-year survival was 88.0%.   There was no increased risk of death based on gender, race or recurrence status.

Conclusion: Patients with subcutaneous GCT treated with excision fair well without adjuvant treatment.  However, patients with multifocal tumors are more likely to experience recurrence and should undergo repeat surgery.

 

47.13 Giant Parathyroid Adenoma – Friend or Foe?

Posted on January 26, 2017

D. J. Goldberg1, J. Monchik1, T. Cotton1  1Brown University School Of Medicine,General Surgery,Providence, RI, USA

Introduction:

Giant parathyroid adenomas are poorly defined in the literature. There is limited data regarding preoperative localization and the incidence of multiglandular disease. The purpose of this study is to determine the utility of preoperative localization using ultrasound and sestamibi, as well as the incidence of multiglandular disease, in patients with a giant parathyroid adenoma.

Methods:

A retrospective review identified 870 patients who underwent surgery for primary hyperparathyroidism (PHPT) from January 2003 to September 2013.  A giant parathyroid adenoma, defined as a single gland with a weight >2 grams, was identified in 78 patients. Seven hundred ninety-two patients had adenomas <2 grams and were placed in the non-giant adenoma group.  All patients underwent ultrasound and sestamibi for preoperative localization.  Ultrasound and sestamibi results were compared with operative findings. The criteria for completion of surgery was an intraoperative parathyroid hormone fall of 50% from the highest level and into the normal range 10 minutes following parathyroid gland resection. Accuracy of various localization techniques, as well as the incidence of multiglandular disease, was then compared between groups.

Results:

In the giant adenoma group (>2 grams), surgery identified a single adenoma in 70/78 patients (89.7%) and double adenoma in 8/78 (10.3%).  There was no incidence of four gland hyperplasia.  In the non-giant adenoma group, surgery identified a single adenoma in 683/792 patients (86.2%), double adenoma in 88/792 (11.1%), and 4 gland hyperplasia in 21/792 (2.7%).  Giant adenomas were correctly localized by ultrasound in 60/78 patients (77%) compared to the non-giant adenoma group with 518/780 patients (66%, p=0.07).  Giant adenomas were correctly localized by sestamibi in 72/78 patients (92%) compared to the non-giant adenoma group with localization of 618/785 patients (79%, p=0.002).  Within the giant adenoma group alone, sestamibi was significantly more accurate at localizing the giant adenoma when compared with ultrasound (92% vs 77%, p=0.01).  Of the 8 patients with a double adenoma in the giant adenoma group, 4/8 (50%) correctly localized one of the two adenomas by ultrasound compared to 7/8 (88%) with sestamibi (p=0.28).

Conclusion:

Giant parathyroid adenomas are reasonably common, occurring in 9% of parathyroidectomies for PHPT over a 10 year period.  While 10.3% of giant adenoma patients had a double adenoma, none had four gland hyperplasia.  Patients with a giant adenoma localized better with sestamibi than ultrasound and were more likely to localize with either modality than patients with non-giant adenomas.  

 

45.08 Initial Experience of Rectal Cancer Staging with 7T Magnetic Resonance Imaging

Posted on January 26, 2017

J. J. Blank2, N. G. Berger2, P. M. Knechtges3, R. W. Prost3, C. Y. Peterson1, K. A. Ludwig1, T. J. Ridolfi1  1Medical College Of Wisconsin,General Surgery, Colorectal Division,Milwaukee, WI, USA 2Medical College Of Wisconsin,General Surgery,Milwaukee, WI, USA 3Medical College Of Wisconsin,Radiology,Milwaukee, WI, USA

Introduction:  The management of rectal cancer relies heavily on Magnetic Resonance Imaging (MRI) for proper staging. MRI is an invaluable but imperfect tool, with tumor depth being reported incorrectly in up to 1/3 of cases. If tumor depth is wrongly reported as too deep or lymph node status is wrongly reported as positive it will relegate the patient to additional unnecessary radiation and chemotherapy. Additionally, 10%–30% of individuals who undergo preoperative chemoradiation are found to have a complete pathologic response.  Some centers are now adopting a ‘‘watch and wait’’ approach, foregoing surgery for high operative risk individuals who have clinical evidence of a complete pathologic response. Resection is still considered standard of care in healthy individuals as no clinically available imaging technology is able to accurately predict complete response. Standard MRI technology currently operates at 3T, a unit of magnetic strength. The Medical College of Wisconsin Center of Imaging Research houses one of only twenty 7T MRIs worldwide. We hypothesize that 7.0 T MRI will accurately predict postoperative tumor depth and nodal status.

Methods:  Patients undergoing low anterior resection for rectal cancer were enrolled in the trial. Patients received neoadjuvant treatment based on current NCCN guidelines. Following excision, the surgical specimen was secured in a normal saline filled canister and subsequently imaged in the 7T MRI. A radiologist blinded to the pathologic data interpreted the specimen images for tumor depth and nodal status. Imaging data was then compared to the pathology reports to determine accuracy.

Results: Between July 2015 and July 2016, 5 patients met inclusion criteria. Radiologic and pathologic interpretation of specimen was identical regarding tumor depth in 3 of 5 patients (60%) Additionally, nodal status was correctly predicted by MRI in 3 of 5 patients (60%). One patient had perfect correlation between radiologic interpretation and pathologic specimen.  

Conclusion: Discrepancy between the pathologic and radiologic staging of the specimens was identified. This is not unexpected as the current project represents the first images of the human rectum obtained at 7T. We anticipate that 7T MRI radiologic staging will become more accurate as specific imaging characteristics of varying stages of rectal cancer are defined. 7T MRI holds promise in accurately staging rectal cancer and possibly predicting response to neoadjuvant therapy. 

 

42.20 Development of Hepatic Injury Model in Rats for Testing Hemostatic Patches

Posted on January 25, 2017

E. Roozen1, R. Lomme1, H. Van Goor1  1RadboudUMC,General Surgery,Nijmegen, GELDERLAND, Netherlands

Introduction:
Intra-operative or traumatic bleeding are common problems in surgery causing significant morbidity and mortality. Hemostatic products are increasingly recognized as an important measure to control bleeding. There is a need for safe, synthetic, cheap and effective alternatives for the already available hemostatic products. Preclinical testing of these products is predominantly performed in pig liver injury models. We develop hepatic injury models in small animals in order to replace the pig model. These models are our first step to ultimately create ex vivo perfusion models in order to reduce, refine and replace (3R’s) animals.  Aim of this study is to explore the consistency in creating a significant bleeding defect of the rat liver to discriminate between different hemostatic patches in terms of efficacy.

Methods:
Two models were evaluated, a liver biopsy punch model and a partial liver resection model . It is known that punch biopsies are reproducible because the surface area and depth have the same dimensions and can be controlled for. Resection models vary more, but have more clinical relevance. Thirty rats were used, in each rat 2 defects were created. In experiment 1, different punch diameters and depths were used to obtain a reproducible and significant bleeding (punch model). In another set of animals partial-lobe resection was performed (resection model). Rats were randomized for either model, receiving an active patch (A1) or a control non-active patch (P1) on both defects. In experiment 2 the feasibility of folding the patch around the edges of the resected area was explored using 2 active patches (A2 and A3).
Outcome for consistency were the severity of bleeding, amount of bloodloss (BL,weight absorbed blood), the surface area of the defect (photodigital planimetry), and the weight of the resected specimen. Outcome for efficacy were time to hemostasis (TTH) and BL after patch application, prior to hemostasis.

Results:
A punch diameter of 8x3mm and the resection created consistent bleedings. 37/60 defects were evaluable for efficacy. There was no difference in TTH (p=0,715) and BL (p=0,440) between the A1 and P1 in the punch model, whereas A1 significantly decreased TTH (p=0,003) and BL (p=0,001) compared to P1 in the resection model. Non-folding was better feasible than folding the patches without differences in TTH and BL. A2 and A3 patches differed in TTH (p:0,02) and BL in both the folding (TTH: p=0,02; BL: p=0.049) and non-folding (TTH: p=0,000 ; BL: p=0.005) application.

Conclusion:
In rats a consistent and easy to operate, partial liver resection model can be created that discriminates between well and worse performing hemostatic products using easy to measure and clinically relevant outcomes.
 

42.13 Thailandepsin-A Decreases Notch1 and Cell Proliferation in Neuroblastoma

Posted on January 25, 2017

Z. Aburjania1, A. Janssen1, S. Jang1, H. Chen1, R. Jaskula-Sztul1  1The University Of Alabama At Birmingham,Surgery,Birmingham, Alabama, USA

Introduction:
Neuroblastoma is a highly aggressive tumor of childhood with 5year survival rate of 68% for children aged 1 to 14 years. It is derived from sympathoadrenal lineage of the neural crest progenitor cells. Notch signaling has important role in determining cell fate during differentiation of ectodermal cells in the sympathetic nervous system. Notch pathway is associated with low differentiation of neuroblastoma, activation of proliferation and motility of cancer cells. Histone deacetylase inhibitors (HDACi) are well-known for their anti-tumor activity as well as their ability to regulate Notch signaling.  We tested a novel HDACi Thailandepsin-A (TDP-A) as a treatment option for neuroblastoma.

Methods:
Methylthiazolyldiphenyl-tetrazolium bromide (MTT) rapid colorimetric assay was used to determine the IC50 of TDP-A on LA-N-5, NGP and SK-N-SH neuroblastoma cell lines. The effect of TDP-A on Notch1 and apoptotic markers p21 and p27 were assessed by western blot after treatment of neuroblastoma cells with DMSO, 3nM and 6nM TDP-A. Additionally N-myc-amplified NGP cell lysates were assessed for N-myc protein levels. Cells were also assessed for neurite outgrowth as a sign of differentiation.

Results:
IC50 was determined to be 4nM, 4nM and 6nM for LA-N-5, NGP and SK-N-SH cell lines respectively. Western blot analysis showed decrease of Notch1 in all cell lines. p27 levels increased with the treatment in LA-N-5 cells. NGP cell line showed increase of p21 protein. N-myc levels decreased in NGP cell lines with the treatment of TDP-A. Increase of neurite outgrowth was observed with the treatment in LA-N-5 cells (12.5um vs 47.8um, p=0.464).

Conclusion:
TDPA has potent anti-proliferating effect on neuroblastoma cell lines in low nanomolar concentrations. It decreased Notch1 in all cell lines together with decrease of N-myc in NGP that is known to have amplified N-myc gene, which is observed in one-third of neuroblastomas and correlated with advanced disease. These results show that TDPA is a promising drug for treatment of neuroblastoma.
 

42.11 Direct Peritoneal Resuscitation Improves Mesenteric Perfusion by Nitric Oxide Dependent Pathways

Posted on January 25, 2017

S. Khaneki1, A. Jensen1, N. Drucker1, T. Markel1  1Indiana University School Of Medicine,Surgery,Indianapolis, IN, USA

Introduction: Direct peritoneal resuscitation (DPR) has been shown to increase survival following intestinal ischemia and reperfusion injury (I/R).  We have previously appreciated that the use of minimal essential medium (MEM) contributes to these survival benefits as well as a reduction in intestinal inflammation. We hypothesized that: 1) DPR using MEM as a dialysate would increase mesenteric perfusion following intestinal I/R, and 2) increased perfusion would be dependent on endothelial nitric oxide pathways.  

Methods: Eight-week-old C57Bl6J wild type (WT) and C57Bl6J eNOS Knock Out (eNOS KO) male mice were anesthetized with isoflurane.  A midline laparotomy was performed and the intestines were eviscerated. Baseline perfusion was measured using Laser Doppler Imaging (LDI).  Intestinal ischemia was then induced by clamping the superior mesenteric artery (SMA) with a non-traumatic vascular clamp for 60 minutes.   Following intestinal ischemia, the clamp was removed and the incision was closed in two layers.  Prior to final closure, 1ml of PBS vehicle or 1 ml of MEM (alpha-minimum essential medium plus 16% fetal bovine serum, 1% penicillin/streptomycin, and 1% glutamine) was injected into the abdominal cavity of the WT and eNOS KO groups. Animals were then allowed to recover for 48 hours.  After this time, animals were reanesthetized, the midline incision opened, and intestinal perfusion reassessed by LDI.  Animals were then euthanized.  Perfusion was expressed as a percentage of baseline and was compared between groups using the Mann-Whitney test.  A p<0.05 was considered statistically significant.

Results:Direct peritoneal resuscitation with MEM significantly improved mesenteric perfusion compared to PBS as measured by laser doppler imaging (WT + Vehicle: 32.85±17.2% vs. WT + MEM: 105.9±6.58%, p<0.05).  The benefits of DPR with MEM were lost when endothelial nitric oxide signaling pathways were ablated (WT + MEM: 105.9±6.58% vs. eNOS KO + MEM: 19.65 ± 5.49%, p<0.05).

Conclusion:Direct peritoneal resuscitation with MEM has significant therapeutic potential for its ability to improve mesenteric perfusion following intestinal ischemia. This benefit appears to be dependent on nitric oxide signaling within the mesenteric endothelium.  Further investigation into additional downstream signaling cascades are essential prior to DPR being implemented in human clinical trials.

 

42.07 Up Regulation of Somatostatin Receptor Expression on Medullary Thyroid Cancers Using HDACi

Posted on January 25, 2017

A. Janssen1, Z. Sun1, Z. Aburjania1, H. Jin1, R. Jaskula-Sztul1, H. Chen1  1University Of Alabama at Birmingham,Department Of Surgery,Birmingham, Alabama, USA

Introduction: Medullary Thyroid Cancers (MTC) are neuroendocrine tumors (NETs) that arise from calcitonin-producing C-cells of the thyroid gland. Although MTCs are slow growing, they are frequently metastatic at the time of discovery and not amenable to curative surgery. They also secrete excessive hormones, often causing debilitating symptoms such as facial flushing and diarrhea. Somatostatin receptors (SSTRs) are a family of five G protein-coupled receptors that are overexpressed in 85% of NETs. SSTRs participate in modulation of neurotransmission, inhibition of hormone secretion, and inhibition of cell proliferation. Somatostatin (SST) analogs have been used for treatment and imaging studies in NETs, but have not shown to be very practical in MTCs due to low or lack of SSTR expression. Herein, we describe the novel use of a class of drugs known as histone deacetylase inhibitors (HDACi) that have the unique ability to up regulate expression of SSTRs on MTCs, and are able to induce expression in patients with no phenotypic expression of SSTRs. The use of HDACi will further advance SST analog therapies and imaging studies in NETs.

Methods: We used Quantitative real time PCR (Q-PCR) to evaluate basal expression of SSTR1 to SSTR5 on two MTC cell lines– MZ and TT– against a positive control pulmonary fibroblast cell WI-38. Time dependent induction of SSTRs was then evaluated with Q-PCR for MZ and TT cells treated with a potent HDACi Thilandepsin-A (TDP-A) at 12, 24, and 48 hours. Furthermore, we assessed dose dependent induction for SSTR1-5 on MZ and TT at 48 hours with four separate HDACi– FK228, SAHA, TDP-A and VPA– using Q-PCR and Western Blot analysis for all treatments.

Results: Basal expression for both cell lines showed an increased expression in one or more SSTRs. MZ cells showed increased expression in SSTR2, SSTR4 and SSTR5, with very low expression of SSTR1. TT cells showed a significant expression of SSTR1 and SSTR2 with no basal expression of SSTR4. After Treatment with all four HDACi, MZ cells showed an eight- to fourteen-fold increase in message for SSTR1 and a two-fold increase in SSTR2. TT cells showed increased expression of SSTR2, SSTR3 and SSTR5. More importantly, TT cells had no basal expression of SSTR4, but treatment showed to induce expression of SSTR4.

Conclusion: We demonstrated that four tested HDACi increased message and protein levels of SSTRs in MTC cells in a time and dose dependent manner. We also showed that HDACi have the capability to induce expression of SSTRs even if there is no basal expression. This novel finding provides an avenue to improve SST analog therapies and imaging studies for MTCs.

42.05 Histologic Changes Following Fish Oil Pretreatment and Hepatic Ischemia Reperfusion Injury

Posted on January 25, 2017

M. A. Baker1, P. Nandivada1, A. Pan1, G. L. Fell1, L. Anez-Bustillos1, D. T. Dao1, K. M. Gura2, V. Nosé3, M. Puder1  1Boston Children’s Hospital,Vascular Biology Program And Department Of Surgery,Boston, MA, USA 2Boston Children’s Hospital,Department Of Pharmacy,Boston, MA, USA 3Massachusetts General Hospital,Department Of Pathology,Boston, MA, USA

Introduction:  Ischemia reperfusion injury (IRI) is a major barrier to liver surgery and transplantation, particularly with steatotic livers. Fish oil lipid emulsions are rich in anti-inflammatory omega-3 fatty acids and the antioxidant alpha-tocopherol. The purpose of this study was to determine if pre-treatment with a single dose of intravenous fish oil (IVFO) can decrease hepatic IRI.

Methods:  Male 6-8 wk old C57BL/6 mice received 1 g/kg IVFO (Omegaven®, Fresenius Kabi) or isovolumetric saline via tail vein injection 1 h prior to suture ligature of the portal triad to the cephalad liver lobes. After 30 min of 70% hepatic ischemia, livers were reperfused. Animals were sacrificed after 4, 8, or 24 h of reperfusion and livers harvested for histologic analysis by a single, blinded, board-certified pathologist. Percent necrosis was calculated using ImageJ software (NIH).

Results: After 4 h of reperfusion, saline-treated livers demonstrated marked ischemia around central veins diffusely, while IVFO-treated livers demonstrated small, scattered foci of necrosis with normal liver between necrotic areas. After 8 h of reperfusion, both saline and IVFO-treated livers demonstrated pale areas of cell loss with surrounding regenerating hepatocytes. There were more regenerating cells around areas of necrosis in IVFO-treated livers, which was confirmed with Ki67 staining and may represent faster recovery. After 24 h of reperfusion, both saline and IVFO-treated livers demonstrated patchy areas of frank necrosis and normal appearing liver, without preference for central vein or portal space, with a decreased overall percent area of necrosis in IVFO-treated livers (saline mean 9.27 ± SEM 2.50 %, n=7 vs. IVFO mean 1.70 ± SEM 0.44 %, n=9; P=0.03). Figure 1 demonstrates representative H&E images of livers after IRI at 200x magnification (open arrows = ischemia, closed arrows = necrosis).

Conclusion: Temporal findings after hepatic IRI suggest IVFO’s hepatoprotective effects may be related to accelerating healing. Specific fatty acid receptor knockout studies are underway to determine the mechanism of this protection.

 

42.04 Characteristics Affecting Virtual Reality Distraction for Pain

Posted on January 25, 2017

J. Harder1, M. De Vries1, H. Van Goor1  1RadboudUMC,Nijmegen, GELDERLAND, Netherlands

Introduction:
Post-surgical pain (PSP) is a difficult to treat condition that requires alternative means to improve patient comfort, physical functioning and quality of life. Virtual reality (VR) has shown to be an distraction tool that can reduce pain perception and expectation and anxiety to suffer from pain. Most studies investigating VR distraction included mostly young patients and did not explore patient or VR characteristics. Our goal was to investigate the effects of two applications (passive or interactive) of VR distraction and their association with personal characteristics such as age, gender, visualisation, imagination, immersion in the virtual world and previous gaming or VR experience.

Methods:
Fifty healthy volunteers (25 M, 25 F, 19 – 66 years of age, mean age 40.9 years) underwent electrical and monofilament tactile perception tests while undergoing three study conditions (control (black screen, no audio), passive VR, interactive VR) in a randomized order using a placebo-controlled, three-way, crossover design. The in-house developed passive and interactive VR applications consisted of the same journey through a river-like landscape, but differed only by a cognitive task (shooting at various targets using head movements) in the interactive VR. Personal characteristics and immersion in the virtual world were gathered using a questionnaire with a 5-point Likert scale design.

Results:
A difference in overall mean of electrical detection threshold and monofilament threshold was observed between each study condition (F(2, 76) = 6.340, p = 0.003 | F(2, 76) = 20.174, p < 0.0005). Interactive VR showed a significant greater beneficial effect as a distraction tool compared to passive VR (p = 0.012). No gender effect was found. There was a positive correlation between age and interactive VR distraction (r = 0.333, p = 0.018). The amount of self-reported immersion in the virtual world showed a positive correlation with an increased effect of distraction by VR (r = 0.352, p = 0.012). Other personal characteristics and previous gaming or VR experience did not affect VR distraction (p > 0.1).

Conclusion:
Passive and interactive VR both distract from pain and tactile sensation, with interactive VR having the largest effect, independent of age and gender. Self reported presence in the VR world enlarged the distraction effect. Previous gaming/VR experience did not affect VR distraction. Future research focuses on personalizing VR applications for a maximum distraction effect to be used as an adjunct to painkillers for post-surgical pain treatment.
 

41.19 Endogenously Expressed IL-10 Contributes to Wound Healing and Regulates Tissue Repair Response

Posted on January 25, 2017

M. M. Rae1, T. Lu1, C. M. Moles1, X. Wang1, M. Fahrenholtz1, H. Li1, P. Duann1, P. Bollylky2, S. Balaji1, S. G. Keswani1  1Texas Children’s Hospital And Baylor College Of Medicine,Division Of Pediatric Surgery,Houston, TX, USA 2Stanford University School Of Medicine,Infectious Diseases And Microbiology And Immunology,Stanford, CA, USA

Introduction:
Our lab has shown a significant role for the anti-inflammatory cytokine IL-10 in regulating inflammation and ECM production, thereby attenuating fibrosis in skin wounds. Previous reports have shown, paradoxically, that wounds in IL-10-/- mice heal faster, with increased rates of re-epithelialization as compared to wildtype mice. However, these wounds were not controlled for contraction and wound environment. Therefore, we sought to determine the role of contraction on IL-10’s wound healing and anti-fibrotic effects in a controlled moist wound environment.

Methods:
Full thickness excisional 6mm wounds were made in IL-10+/+ and IL-10-/- mice that were controlled for contraction using a silicone stent. A consistent and moist wound environment was provided by semi-occlusive dressing Tegaderm. Wounds were serially photographed at 3, 5 and 7d and harvested at 7d and 14d post wounding, then examined for epithelial gap, granulation tissue (H&E), myofibroblasts (a-SMA staining) and leucocyte infiltration (CD45). Data is presented as mean+/-SD, n=5 wounds/group/time point; p-value by ANOVA.

Results:
Macroscopic appearance of unstented wounds with no dressing showed accelerated wound closure in IL-10-/- mice by day 7 compared to controls(IL-10+/+). This effect was lost when a semi-occlusive wound dressing was applied to unstented wounds to create a consistent moist wound environment, with no significant differences observed in re-epithelialization(IL-10-/- 2380±508.4 vs IL-10+/+ 2480.4.7±824.6, p=ns), epithelial gap (IL-10-/- 1433.7±558.1 vs IL-10+/+ 1436.2±527.7, p=ns), granulation tissue (IL-10-/- 1.65±0.5 vs IL-10+/+ 1.21±0.4, p=ns), or CD45 positive cells (IL-10-/- 10.1%±6.2 vs IL-10+/+ 8.9%±4.2, p=ns). In unstented wounds, a-SMA was abundantly expressed at the wound margins, but in IL-10-/- wounds, a-SMA was present throughout the granulation tissue and extended into deep dermal layers, whereas a-SMA expression was less pronounced in the IL-10+/+ wound bed. Stenting of wounds, which controlled for the contractility of mouse skin, significantly delayed wound healing. However, there was no statistical difference in either epithelial gap (IL-10-/- 4883.5±610.8 vs. IL-10+/+  4152.2.7±480.6, p=ns) or granulation tissue (IL-10-/- 0.33±0.1 vs. IL-10+/+  0.55±0.2, p=ns) at day 7, although stented IL-10-/- wounds exhibited increased a-SMA density. Interestingly, the CD45+ cellular infiltrate significantly increased in stented IL-10-/- mice as compared to unstented (IL-10-/- 10.1%±6.2 vs. IL-10-/- with stent 32.8%±15.6, p<0.01), but did not change in IL-10+/+ mice. Finally, wounds in IL-10-/- mice also developed significantly more scar tissue and much thicker epidermis on day 14 compared to IL-10+/+ mice. 

Conclusion:
IL-10 expression does not delay normal wound healing of skin wounds when wounds are controlled for contraction and moist environment. However, the loss of IL-10 leads to increased fibrosis. This data signifies a previously unrecognized role for endogenously expressed IL-10 contributing to the tissue repair response.  
 

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