27.09 Defining Surgeon Volume Threshold for Improved Outcomes From Minimally Invasive Colectomy

Posted on January 18, 2018

M. A. Adam1, D. Becerra1, M. C. Turner1, C. R. Mantyh1, J. Migaly1  1Duke University Medical Center,Department Of Surgery,Durham, NC, USA

Introduction: The association between surgeon volume and improved outcomes for minimally invasive colectomy (MIC) has been established. However, a definition of a high-volume MIC surgeon remains unclear. We aimed to determine the number of MIC per surgeon per year that is associated with the lowest risk of postoperative complications. 

Methods: Adult patients undergoing MIC were identified from the HCUP-National Inpatient Sample (2008-2009). Multivariabe logistic regression with restricted cubic splines was utilized to examine the association between the number of annual MIC/surgeon and risk of complications.

Results: 6554 patients were identified; 51% had a diagnosis of colon cancer. Overall, 20% experienced a postoperative complication and 0.5% died in hospital. Median surgeon volume was 10 cases/year. After adjustment for case and procedure mix, the likelihood of experiencing a complication decreased with increasing surgeon volume up to 20 MIC cases/year (p<0.01) (Figure). The vast majority of patients (70%) underwent surgery by low-volume (<20 cases/year). Patients treated by low volume surgeons were more likely to experience conversion to open colectomy (0.8% vs. 0.3%), postoperative complications (21% vs. 17%), prolonged hospital length of stay (6 vs. 5 days), and higher inflation-adjusted hospital costs ($12669 vs. $11752), (all p<0.01). 

Conclusion:  This study identifies a surgeon volume threshold (>20 cases/year) that is associated with improved patient outcomes from minimally invasive colectomy. Identifying a threshold number of cases defining a high-volume MIC surgeon is important, as it has implications for quality improvement, criteria for referral and reimbursement, and surgical education.

 

27.10 Postoperative Morbidity Independently Predicts Cancer-Related Survival in Peritoneal Metastases

Posted on January 18, 2018

H. A. Choudry1, Y. Shuai2, J. F. Pingpank1, M. P. Holtzman1, S. S. Ahrendt1, H. L. Jones1, L. Ramalingam1, A. H. Zureikat1, H. J. Zeh1, D. L. Bartlett1  1University Of Pittsburgh Medical Center,Surgical Oncology,Pittsburgh, PA, USA 2University Of Pittsburgh Cancer Institute,Biostatistics Facility,Pittsburgh, PA, USA

Introduction: Postoperative morbidity may negatively impact cancer-related outcomes by inducing a pro-tumorigenic environment and preventing the timely initiation of postoperative systemic therapy. We hypothesized that postoperative morbidity would predict cancer-related survival, independent of tumor histology, grade, extent of disease, and other comorbidities. 

Methods: We addressed our hypothesis by using a prospective database of 1296 patients with peritoneal metastases undergoing complex surgical resection with high postoperative morbidity and long-term cancer-related mortality rates. We graded all postoperative morbidity using the Clavien-Dindo grading system. Kaplan-Meier method was used to estimate survival.  Multivariate analyses identified associations with survival and postoperative morbidity.

Results: Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion was performed for peritoneal metastases from cancers of the appendix (50%), colorectum (30%), ovary (8%) and mesothelioma (12%). Tumor burden assessed by median peritoneal carcinomatosis index (PCI) was 16 and optimal cytoreduction (residual tumor < 2.5mm) was achieved in 93% of patients. Major postoperative morbidity (Clavien-Dindo grades 3-5) occurred in 24% of patients and long-term cancer-related mortality was 53%, after a median follow-up of 55 months. Median progression-free survival and overall survival calculated from surgery were 15 and 39 months, respectively. In a multivariate Cox proportional hazards model, major postoperative morbidity (Clavien-Dindo grades 3/4) was an independent negative predictor of survival (HR 1.4) along with non-appendiceal primary histology, higher tumor grade, higher PCI, incomplete cytoreduction, higher age-adjusted Charlson comorbidity index, and recurrent symptomatic disease at presentation. Patients with grades 3/4 postoperative morbidity were 1.6/2.5 times more likely to die of their cancer than those with no post-operative complications. Using multivariate logistic regression model, independent predictors of major postoperative morbidity included higher preoperative ASA (American Society of Anesthesiologists) physical status classification, longer operative time, higher PCI, and non-appendiceal primary histology. 

Conclusion: In our experience, postoperative morbidity independently predicted cancer-related survival, regardless of comorbidities, tumor type, extent, grade, and completeness of surgery. Future work will focus on mechanism underlying this phenomenon. Moreover, the extent of surgical resection required to clear the disease played a dominant role in predicting occurrence of postoperative morbidity. Ongoing studies will address optimization of selection criteria and perioperative management strategies that may reduce postoperative morbidity in such patients that frequently require lengthy procedures and multi-visceral resections. 

 

27.08 Predictive Value of Leukocyte and Platelet-derived Ratios in Locally Advanced Rectal Adenocarcinoma

Posted on January 18, 2018

W. H. Ward1, A. C. Esposito2, N. Goel1, K. J. Ruth3, E. R. Sigurdson1, J. E. Meyer5, C. S. Denlinger4, J. M. Farma1  1Fox Chase Cancer Center,Department Of Surgical Oncology,Philadelphia, PA, USA 2Temple University,Lewis Katz School Of Medicine,Philadelpha, PA, USA 3Fox Chase Cancer Center,Biostatistics And Bioinformatics Facility,Philadelphia, PA, USA 4Fox Chase Cancer Center,Department Of Hematology/Oncology,Philadelphia, PA, USA 5Fox Chase Cancer Center,Department Of Radiation Oncology,Philadelphia, PA, USA

Introduction:
Although advances in the multidisciplinary treatment of locally advanced rectal cancer have improved survival, there is variability in response to therapy. In addition to tumor biology, host factors and immunologic capacity may play a role. Given the morbidity of therapy and risk of recurrence, there is much interest in preoperative identification of predictive biomarkers.  In colorectal cancer, recent data suggest the utility of the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in predicting survival. The aim of our study was to examine these factors in our rectal cancer patients and determine whether any association exists between these ratios and overall survival.  

Methods:
Using data from a prospectively maintained database at our tertiary referral center, a query was completed for all patients with clinical stage II to III rectal adenocarcinoma who underwent comprehensive treatment from 2002-2016.  We included patients with full demographic, staging, treatment, and survival data who had a complete blood count collected prior to neoadjuvant chemoradiation (pre-CRT) and again prior to surgery (post-CRT).  LMR, NLR, and PLR were calculated for the pre-CRT and post-CRT time points.  Potential cutpoints associated with overall survival (OS) differences were determined using the maxstat R package, which identifies optimal cutpoints while controlling for repeat testing (p<0.05). Survival curves based on these cutpoints were compared using log-rank tests and were adjusted for age and stage using Cox regression.

Results:
A total of 146 patients were included.  Cutpoints were significantly associated with OS for pre-CRT ratios but not for post-CRT ratios.  Within the pre-treatment group, “low” (<2.86) LMR was associated with decreased OS (log-rank p=0.004, 5 year OS= 69% [95%CI 54%-80%]) compared to “high” (>2.86) LMR (5 year OS= 86% [95%CI 75%-93%]).  In the same group, “high” NLR (>4.47) was associated with decreased OS (log-rank p<0.001), and “high” PLR (>203.6) was associated with decreased OS (log-rank p<0.001).  With adjustment for age and final pathologic stage, the associations of NLR and PLR with OS retained their statistical significance (p=0.017 and p=0.005, respectively), and the association of LMR and OS had borderline statistical significance (p=0.075).

Conclusion:
If obtained prior to the start of neoadjuvant chemoradiation, LMR, NLR, and PLR values are accurate predictors of 5-year OS in patients with locally advanced rectal adenocarcinoma.  Following the administration of neoadjuvant therapy, these ratios lose their predictive ability.  Further confirmation of the value of these ratios in larger datasets will be important.
 

27.07 Post-Discharge Opioid Utilization after Colorectal Surgery is Modified by ERAS Pathways

Posted on January 18, 2018

K. E. Hudak1, L. E. Goss2, R. K. Burton3, P. K. Patel1, E. A. Dasinger2, G. D. Kennedy2, J. A. Cannon2, M. S. Morris2, J. S. Richman2, D. I. Chu2  1University Of Alabama at Birmingham,School Of Medicine,Birmingham, Alabama, USA 2University Of Alabama at Birmingham,Department Of Gastrointestinal Surgery,Birmingham, Alabama, USA 3University Of Alabama at Birmingham,School Of Public Health,Birmingham, Alabama, USA

Introduction:  The excess utilization of opioids after surgery is common and may contribute to the national opioid epidemic. Enhanced Recovery After Surgery (ERAS) pathways have been shown to decrease in-hospital opioid utilization, but their effect on post-discharge opioid utilization is unclear. We hypothesized that patients undergoing ERAS for colorectal surgery would have decreased opioid utilization on discharge and at one-year post-discharge.

Methods:  A single-institution ERAS database was used to identify all patients undergoing colorectal surgery in 2015. ERAS patients were then matched by sex, race, age, indication, and procedure with pre-ERAS patients from 2013-14 to create a comparison group. Patient/procedure-level characteristics were included. Excluded were patients who died within one year of surgery, long-term dependent opioid users, and opioid users above the 99th percentile of oral morphine equivalents (OME). Outcomes evaluated included OME at discharge, total OME within 1-year, OME per pill (OME/P) at discharge, opioid type, and pill counts. Variables with p<0.05 on bivariate comparisons were included in adjusted linear models.

Results: Of 395 patients included in this study, 89.6% were prescribed an opioid on discharge. Pre-ERAS (n=197) and ERAS (n=198) patients were similar by matched characteristics and smoking status, ASA class, hypertension and diabetes. Compared to pre-ERAS patients, ERAS patients had more minimally invasive surgeries (43.4% vs. 32.5%), more ostomies (38.9% vs. 25.9%) and had lower rates of baseline opioid use (15.2% vs. 29.4%) (p<0.03). More ERAS patients were discharged with no opioids compared to pre-ERAS patients (13.1% vs. 7.6%, p=0.07). Among those discharged with opioids, ERAS patients received an average of 403 OME and 60.6 pills vs. 343 OME and 46.9 pills for pre-ERAS (p<0.03 for all). However, the OME/P at discharge was significantly lower for ERAS (6.9 vs. 7.6, p<0.01), which remained after adjustment for covariate differences (7.0 vs 7.9, p=0.01). ERAS patients used more low-OME medications, such as tramadol (35.9% vs. 0%, p<0.001) and were prescribed fewer high-OME medications containing hydrocodone or oxycodone (37.9% vs. 72%, p<0.01). At one-year post-discharge, ERAS patients received fewer additional high-OME prescriptions (34.3% vs. 43.7%, p<0.01).

Conclusion: ERAS modifies post-discharge opioid utilization for patients undergoing colorectal surgery. On discharge, more patients undergoing ERAS required no opioids and at one year, ERAS patients required less opioid prescriptions. While ERAS patients discharged with opioids did receive more OMEs overall, these OMEs were distributed over more pills and ERAS patients actually received more low-potency (low OME) pills, accounting for a lower OME/P ratio. These findings suggest a potential role for ERAS in reducing post-discharge opioids utilization and an additional need to standardize post-discharge prescriptions patterns.

 

27.04 A Preoperative Prediction Model for Risk of Multiple Admissions after Colon Cancer Surgery

Posted on January 18, 2018

J. H. Fieber1, C. E. Sharoky1, K. Collier1, R. L. Hoffman1, C. Wirtalla1, E. C. Paulson1, G. C. Karakousis1, R. R. Kelz1  1University Of Pennsylvania,Department Of Surgery,Philadelphia, PA, USA

Introduction: Colon cancer treatment commonly has a profound impact on patients’ and caregivers’ ability to maintain their involvement in the work force, potentially leading to loss of insurance and income. The use of medical services, including multiple hospital admissions [MuAdmin], contributes to time lost at work. We developed a simplified model to predict preoperative risk of MuAdmin amongst patients undergoing colon resection to help patients prepare for treatment and to guide improvement efforts.

Methods: Patients ≥18 years-old with colon cancer that underwent elective surgical resection without postoperative complications identified in discharge claims from California and New York (2008-2011) were included. The primary outcome factor, MuAdmin, was defined as the 90th percentile for admissions following resection. Logistic regression models were developed to identify factors predictive of MuAdmin. A weighted point system was developed using beta-coefficients (β) (p<0.05). A point value of 1 was assigned to β<0.5, 2 was assigned to 0.5≤β<1, and 3 was assigned to β≥1.   A random sample of 75% of the data was used for model development leaving a 25% sample for validation.

Results: A total of 14,805 patients underwent colon surgery with 27.3% requiring at least 1 admission. MuAdmin, defined as ≥2 admissions following resection, impacted 9.7% of patients.  The statistically significant predictors of MuAdmin were Elixhauser comorbidity index ≥3 (β=0.30), metastasis (β=0.96), payer system (Medicare β=0.25, Medicaid β=0.58), and the number of prior admissions in the year before resection (1: β=0.43, 2: β=0.54, 3: β=1.45). Scores ranged from 0-8. Scores ≤1 had <7% risk of MuAdmin, scores between 2-5 had at 10-21% risk of MuAdmin and scores ≥6 had a >30% risk of MuAdmin. Our prediction model accurately stratified patients by the likelihood of MuAdmin. [Table 1: Observed and Predicted Rates of MuAdmin following Colon Cancer Resection by Risk Score]

Conclusion: Following discharge after resection of colon cancer, almost a third of patients are admitted at least once and nearly 10% require 2 or more admissions in the year following surgery.  A simple, preoperative clinical model can predict the likelihood of multiple admissions in patients anticipating resection.  This information can assist patients and caregivers in managing time off from work to minimize the threat of unemployment and financial hardship.

27.05 Fecal Microbiota Transplant Protocol Implementation: A Community-Based University Hospital Experience

Posted on January 18, 2018

R. Duarte-Chavez2, T. R. Wojda1,3, B. Geme1, G. Fioravanti2, S. P. Stawicki3  1St. Luke’s University Health Network,Division Of Gastroenterology,Bethlehem, PA, USA 2St. Luke’s University Health Network,Department Of Internal Medicine,Bethlehem, PA, USA 3St. Luke’s University Health Network,Department Of Surgery,Bethlehem, PA, USA

Introduction: Clostridium difficile (CD) is a serious and increasingly prevalent healthcare associated infection. The pathogenesis of CD infection (CDI) includes the acquisition of CD with a disruption of the native gut flora. Antibiotics are a major risk although other contributors have been identified. Management combines discontinuation of the offending agent, initiation of CD-specific antibiotic(s), probiotic use, fecal microbial transplantation (FMT), and surgery as the “last resort” option. The aim of this study is to review short-term clinical results following the implementation of FMT protocol at our community-based University hospital.

Methods: Following IRB / Infection Control Committee approvals, FMT protocol was implemented for patients with CDI. Prospective tracking of FMT procedures (Jul 1, 2015-Feb 1, 2017) was conducted using REDCap™ data capture system. Indications for FMT included: (a) ≥ 3 CDI recurrences; (b) ≥2 hospital admissions with severe CDI; or (c) first episode of complicated CDI (CCDI). Risk factors for CDI and treatment failure were assessed. Patients were followed for ≥3 months to assess cure/failure, relapse and side effects. Frozen 250 mL FMT samples were acquired from OpenBiome (Somerville, MA). After 4 hrs of thawing, the liquid suspension was applied colonoscopically, from terminal ileum to mid-transverse colon. Recorded data included disease severity (Hines VA CDI Severity Score, HVCSS), concomitant medications, number of FMT treatments, non-FMT therapies, cure rates, and mortality.

Results: Thirty-five patients (mean age 58.5 yrs, 69% female) received FMT, with primary cure in 30 (86%) cases. Within this sub-group, 2/30 (6.7%) patients recurred and were subsequently cured with long-term oral vancomycin (OV). Among 5/35 (14%) primary FMT failures, 3 (60%) were cured with long-term OV and 2 (40%) required colectomy. For the 7 patients who either failed FMT or recurred, long-term OV was curative in all but 2 cases (Fig 1). For patients with severe CDI (HVCSS ≥3), primary / secondary cure rates were 6/10 (60%) and 8/10 (80%), respectively. Patients with CCDI (n=4) had higher HVCSS (4 vs 3) and mortality of 25%. Characteristics of patients who failed initial FMT included older age (70 vs 57 yrs), female sex (80% vs 67%), severe CDI (80% vs. 13%), as well as opioid use during the initial infection (60% vs 37%) and at the time of FMT (60% vs 27%). Most commonly reported side effect of FMT was loose stools.

Conclusion: This study supports the efficacy and safety of FMT in the setting of CDI, with primary (86%) and secondary (71%) non-surgical cure rates being consistent with previous reports. The potential role of opioid use as a modulator of CDI warrants further study.

27.06 Colon Cancer Stages I-III: Why Roam When You Can Resect Near Home?

Posted on January 18, 2018

O. K. Jawitz1, M. Turner1, M. Adam1, C. Mantyh1, J. Migaly1  1Duke University Medical Center,Department Of Surgery,Durham, NC, USA

Introduction:
Cancer resections performed at high-volume colorectal surgery centers are associated with improved post-operative outcomes including fewer complications such as anastomotic leak and increased survival. It is not known if patients who do not live in proximity to high-volume centers benefit from choosing to travel to these institutions as opposed to receiving their care at local, low-volume centers. 

Methods:
The 2006-2014 National Cancer Database (NCDB) was queried for patients with pathologic stage I-III colon adenocarcinoma who underwent cancer treatment at a single center. Travel distances to treatment centers were calculated. Matching the first and fourth quartiles of travel distance with first and fourth quartiles of institution surgical volume established short distance/low-volume (local) and long distance/high-volume (travel) cohorts. The primary outcome of interest was overall survival compared between the local and travel cohorts. Secondary outcomes included incidence of positive resection margins, adequate lymph node harvesting, length of stay, readmission rates, 30-day and 90-day mortality, and use of adjuvant chemotherapy.

Results:
A total of 33,339 patients met inclusion criteria, including 18,163 patients that traveled ≤2.6 miles to centers that performed ≤ 34 resections per year (local) and 15,176 patients that traveled ≥ 21.8 miles to centers that performed ≥ 83 resections annually (travel). In unadjusted analysis, patients in the travel cohort had lower rates of positive resection margins (3.3% vs. 5.0%, p<0.001), more frequently had adequate lymph node harvests (88.9% vs. 79.2%, p<0.001), and had lower 30-day (2.4% vs. 4.0%, p<0.001) and 90-day mortality (4.0% vs. 6.6%, p<0.001). On multivariable logistic regression analysis adjusting for patient demographic, tumor, and facility characteristics, traveling longer distances to high-volume centers remained an independent predictor of improved overall survival (hazard ratio 0.84, p<0.001) and secondary outcomes of adequate lymph node harvesting (OR 0.48, p<0.001), negative resection margins (OR 0.65, p<0.001), lower readmission rates (OR 0.84, p<0.001), 30-day mortality (OR 0.75, p<0.001), and 90-day mortality (OR 0.74, p<0.001). 

Conclusion:
For patients with stage I-III colon cancer who do not live in proximity to high-volume colorectal surgery centers, traveling to these institutions as opposed to receiving treatment at local low-volume centers conveys a postoperative survival advantage. Additionally, rates of adequate oncologic resections and readmission are superior to those who seek care locally. Patients with stage I-III colon cancer should be encouraged to undergo surgical resection at high-volume centers, even if this involves traveling outside of their local region. 
 

27.03 Colorectal Surgical Site Infection Prevention Kits Prior to Elective Colectomy Improves Outcomes

Posted on January 18, 2018

S. E. Deery1, S. T. McWalters2, S. R. Reilly3, H. N. Milch1, D. W. Rattner1, E. A. Mort3,4, D. C. Hooper5, M. G. Del Carmen1,6, L. G. Bordeianou1  1Massachusetts General Hospital,Colorectal Center,Boston, MA, USA 2Massachusetts General Hospital,Edward P. Lawrence Center For Quality And Safety,Boston, MASSACHUSETTS, USA 3Massachusetts General Hospital,Department Of Patient Safety And Quality,Boston, MASSACHUSETTS, USA 4Massachusetts General Hospital,Department Of General Internal Medicine,Boston, MASSACHUSETTS, USA 5Massachusetts General Hospital,Division Of Infectious Diseases,Boston, MASSACHUSETTS, USA 6Massachusetts General Hospital,Department Of Obstetrics And Gynecology,Boston, MASSACHUSETTS, USA

Introduction:
Patient compliance with preoperative mechanical and antibiotic bowel preparation, skin washes, carbohydrate loading, and avoidance of fasting are key components of successful colorectal ERAS and surgical site infection (SSI)-reduction programs. In July 2016, we began a quality improvement project distributing a free SSI Prevention KIT (SSIPK) containing patient instructions (Figure), mechanical and oral bowel preparation, chlorhexidine washes, and carbohydrate drink to all patients scheduled for elective colectomy, with the goal of improving patient compliance and rates of SSI.

Methods:
This was a prospective data audit of our first 221 SSIPK+ patients, who were compared to historical controls (SSIPK-) of 1,760 patients undergoing elective colectomy (1/1/13–3/31/17). A 1:1 propensity score system accounted for nonrandom treatment assignment with the Chi square test to compare matched patients’ compliance and complications.

Results:
SSIPK+ (N=219) and SSIPK- (N=219) matched patients were statistically identical on demographics, comorbidities, BMI, surgical indication, surgeon, and procedure. SSIPK+ patients had higher compliance with mechanical (95% vs. 71%, P < 0.001) and oral antibiotic (94% vs. 27%, P < 0.001) bowel preparation. This translated into lower overall SSI rates (5.9% vs. 11.4%, P = .04). SSIPK+ patients also had lower rates of anastomotic leak (2.7% vs. 6.8%, P = 0.04), prolonged postoperative ileus (5.9% vs. 14.2%, P < .01), and unplanned intubation (0% vs. 2.3%, P = .02). Furthermore, SSIPK+ patients had shorter mean hospital length of stay (3.1 vs. 5.4 days, P < .01) and had fewer unplanned readmissions (5.9% vs. 14.6%, P < .001). There were no differences in rates of postoperative pneumonia, urinary tract infection, Clostridium difficile colitis, sepsis, or death. 

Conclusion:
Provision of a free-of-charge SSIPK improves patient compliance with preoperative instructions, which is associated with significantly lower rates of surgical site infections, lower rates of prolonged postoperative ileus, and shorter hospital stays with fewer readmissions. Widespread utilization of such a kit could therefore lead to significantly improved outcomes and lower costs.
 

27.01 Impact of Mental Health Diagnoses and Treatment on Outcomes after Colorectal Cancer Surgery

Posted on January 18, 2018

C. G. Ratcliff1,4,5, N. N. Massarweh2,5, S. Sansgiry5,6, L. Dindo1,5, H. Yu5,6, D. H. Berger2,5,7, J. A. Cully1,5  1Baylor College Of Medicine,Department Of Psychiatry & Behavioral Sciences,Houston, TX, USA 2Baylor College Of Medicine,Department Of Surgery,Houston, TX, USA 4Sam Houston State University,Department Of Psychology,Hunstville, TX, USA 5Michael E. DeBakey Veterans Affairs Medical Center,Houston, TX, USA 6Baylor College Of Medicine,Department Of Medicine,Houston, TX, USA 7Baylor St. Luke’s Medical Center,Houston, TX, USA

Introduction:  Data regarding the impact of mental health (MH) diagnosis and treatment on postoperative outcomes are evolving.  Presently, little is known about the prevalence and effect of MH treatment on outcomes following surgery for colorectal cancer (CRC).

Methods:  We identified 58,961 Veterans who underwent CRC surgery from 2000-2014 using Veteran Affairs (VA) Surgical Quality Improvement Program (VASQIP) linked to the VA Corporate Data Warehouse to identify MH diagnoses and services. Multivariable logistic regression adjusting for clinical and demographic factors was used to evaluate the association between MH diagnosis (defined as depression, anxiety, PTSD, bipolar, psychotic, personality, cognitive, and substance use disorders) that were documented 30d prior to surgery and the occurrence of 1+ postoperative complication (POCOMP), 90d readmission (90dReadm), and length of stay (LOS). The impact of MH treatment (defined as psychiatric medication and psychotherapy [meds+therapy], psychiatric medication alone [meds alone], psychotherapy alone [therapy alone], or no treatment) within the 30d prior to surgery was also examined.

Results: Within the cohort, 9,029 (15%) had a MH diagnosis (depression = 2,738 [30%], anxiety = 942 [10%], PTSD = 1,762 [20%], bipolar = 505 [6%], psychotic = 679 [8%], cognitive = 239 [3%], personality = 105 [1%], substance use = 4,579 [51%]). Among Veterans with a MH diagnosis, 136 (2%) received meds+therapy, 4,157 (46%) meds alone, 308 (3%) therapy alone, and 4,428 (49%) no treatment during the 30d before surgery.

POCOMP occurred in 30% and 90dReadm in 23% of Veterans. Median LOS was 8d (IQR 6). MH diagnosis was associated with greater odds of POCOMP (OR: 1.10, CI: 1.05-1.16), 90dReadm (OR: 1.10, CI: 1.04-1.16), and longer LOS (OR: 1.42, CI: 1.09-1.86) compared to no MH diagnosis.

Veterans with a MH diagnosis who received no preoperative MH treatment (OR: 1.08, CI: 1.00-1.15) or meds alone (OR: 1.15, CI: 1.07-1.24) had greater odds of POCOMP relative to Veterans without MH diagnosis. Similarly, Veterans with a MH diagnosis who received no preoperative MH treatment (OR: 1.13, CI: 1.04-1.21) or meds alone (OR: 1.15, CI: 1.07-1.24) had greater odds of 90dReadm relative to Veterans without MH diagnosis. Finally, Veterans with a MH diagnosis who received meds alone had longer LOS relative to Veterans without MH diagnosis (OR: 1.96, CI: 1.35-2.85). Odds of POCOMP, 90dReadm, and longer LOS for Veterans with a MH diagnosis who received meds+therapy or therapy alone did not statistically differ from Veterans without MH diagnoses.

Conclusion: MH diagnoses are associated with postoperative complications and readmissions among Veterans who undergo CRC surgery. Provision of preoperative psychotherapy, alone or in combination with psychiatric medication, may help mitigate the adverse effect of psychiatric conditions. Since few Veterans receive adequate preoperative MH treatment, screening for these psychiatric risk factors may be warranted.

27.02 Induction Chemotherapy versus Standard Treatment for Locally Advanced Rectal Cancer

Posted on January 18, 2018

C. Nganzeu1, J. J. Blank1, F. Ali1, W. Hall2, C. Peterson1, K. Ludwig1, T. Ridolfi1  2Medical College Of Wisconsin,Department Of Radiology,Milwaukee, WI, USA 1Medical College Of Wisconsin,Department Of Colorectal Surgery,Milwaukee, WI, USA

Introduction:
The standard treatment of stage II or III rectal adenocarcinoma is chemoradiation therapy (CRT) followed by surgical resection and adjuvant systemic chemotherapy. Recently there has been increased interest in the use of induction chemotherapy (IC), an approach that provides some or all systemic chemotherapy and CRT in the preoperative setting. Potential benefits of this treatment paradigm include tumor downstaging, early treatment of micrometastases, increased rate of sphincter preservation, decreased time with a diverting stoma, and patient compliance. However, little is known about this treatment strategy on a national level. The aims of this study were to define the frequency of IC use and evaluate treatment outcomes compared to standard CRT using the National Cancer Database.

Methods:
The National Cancer Database was queried for patients diagnosed with stage II or III rectal adenocarcinoma having received radiation, chemotherapy and surgical resection between 2004 and 2014. We compared patients with IC to patients having received standard combined CRT. Linear regression was performed to predict percent patients receiving IC by year. Propensity score matching was applied in a 1:10 fashion. A logistic model was fitted to obtain propensity scores. A greedy matching algorithm was then applied for predictor selection. Outcomes including downstaging, readmission, positive margins, and survival were evaluated.

Results:
A total of 33,480 patients met inclusion criteria. 96.4% of patients underwent standard CRT while 3.6% underwent IC. Of all patients diagnosed with stage II and III rectal cancer, only 2.8% received IC in 2004; this number rose to 4.4% in 2014. Propensity score matching yielded 10,531 patients receiving standard CRT and 1,073 patients who received IC for the analysis. The IC group had more tumor downstaging than standard CRT on surgical pathology (54% vs. 48.8%, p=0.006, respectively). This group also had significantly fewer 30-day readmissions after surgery (4.5% vs. 6.4%, p=0.021, respectively). There were no differences observed in 30-day or 90-day mortality (0.5% vs. 0.5%, p= 0.247 and 0.8% vs. 1.1%, P= 0.755, respectively), rate of positive margins (4.8% vs. 5.6%, p=0.398, respectively), or survival (p=0.587) between the two groups.

Conclusion:

The use of induction chemotherapy for patients with stage II and III rectal cancer increased significantly from 2004-2014. Induction chemotherapy was associated with improved downstaging before surgery and improved 30-day readmission rates after surgery without changing overall survival when compared to standard chemoradiation therapy.

 

26.09 Non-Home Discharge and Prolonged Length of Stay after Cytoreductive Surgery and HIPEC

Posted on January 18, 2018

D. Burguete1, A. A. Mokdad2, M. M. Augustine2, R. Minter2, J. C. Mansour2, M. A. Choti2, P. M. Polanco2  1University Of Texas Southwestern Medical Center,Dallas, TX, USA 2University Of Texas Southwestern Medical Center,Division Of Surgical Oncology,Dallas, TX, USA

Introduction:  The ability to preoperatively anticipate prolonged length of stay (PLOS) or transition to an extended care facility (non-home discharge, i.e., NHD) may facilitate discussion of patient expectations and improve utilization of hospital resources. Predictive models for NHD after some major surgical procedures have already been proposed. No data has been reported on the rate and risk factors associated with NHD and PLOS in patients following cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis. The aim of this study is to identify risk factors for NHD and PLOS following CRS/HIPEC in a national cohort of patients.

 

Methods:  The National Surgical Quality Improvement Program (NSQIP) dataset was queried for patients who underwent CRS/HIPEC between 2011-2012. Patients designated as NHD and PLOS (>30d) were compared to the group of patients discharged to home within 30 days. Univariate analysis was used to compare patient demographics, preoperative labs, comorbidities, and intra and peri-operative variables among both groups. Multivariate analysis was used to identify independent predictors of NHD and PLOS.

 

Results: A total of 556 patients who underwent CRS/HIPEC were identified, of which 44 (7.91%) had a NHD/PLOS. From this group, 12 (27.2%) were discharged to a skilled care facility, 11 (25%) were discharged to a rehabilitation facility, and 21 (47.7%) remained hospitalized at 30 days. On univariate analysis, advancing age, chronic obstructive pulmonary disease, hypertension, low preoperative albumin and low preoperative platelets were identified as preoperative risk factors for NHD/PLOS (p values < 0.05). On multivariate analysis, age ≥ 65, pre-op albumin < 3.0 g/dL, and having a multi-visceral resection were identified as independent predictors of NHD/PLOS (Table 1.). If all three predictors are met, the probability of NHD/PLOS is 30.2%.

 

Conclusion: In this national cohort of patients, advanced age, hypoalbuminemia, and multi-visceral resection constituted the main risk factors for NHD/PLOS following CRS/HIPEC. Adequate identification of these risk factors may facilitate preoperative discussions with patients, and improve discharge planning and resource utilization. 

 

 

26.10 Molecular Profiling in Patients with Nodular verus Superficial Spreading Melanoma

Posted on January 18, 2018

M. Renzetti1, I. Solimon1, K. Loo1, E. Lamb1, H. Wu1, B. Luo1, H. Liu1, A. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, J. Farma1  1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA

Introduction: The use of next generation sequencing (NGS) molecular profiling has become increasingly important in characterizing cancers and their subtypes. Our institution has been using NGS to examine mutations in 50 cancer-related genes. It is well established that the nodular subtype of malignant melanoma (MM) tend to be more invasive, ulcerated, and have more mitoses than superficial spreading subtype (SS). Here we examine the use of molecular profiling of patients who presented with either SS or nodular type MM.

Methods:  Patients with either SS or nodular type MM were included in the study. Using NGS, we analyzed tissue samples for mutations in targeted regions of 50 cancer-related genes. Clinical and pathologic data were collected.

Results: We performed NGS on 179 patients with MM. Of these, 51 patients presented with nodular type MM, and 46 with SS type.  Median age at diagnosis was 64 for nodular and 59 for SS (range 22-81). 65.3% and 74% were male in nodular and SS respectively. Location of the primary included head and neck (8 nodular, 4 SS), upper extremity (15 nodular, 11 SS), lower extremity (11 nodular, 10 SS) and truncal (17 nodular, 21 SS).  At presentation, 2 nodular and 7 SS were stage I, 19 nodular and 7 SS were stage II, 26 nodular and 31 SS were stage III, and 4 nodular and 1 SS were stage IV.  Of the tissue tested, 53% (n=51) were from the primary tumor.  In the nodular type, 86 total mutations were identified over 43 unique genes, and in SS type, 73 mutations were identified affecting 35 unique genes (p = 0.34).

In nodular type, no mutations were found in 16% of patients (n=8), while 43% of patients (n=13) had one mutation, 24% (n=12) had 2 mutations, 14% (n=7) had 3 mutations, and 10% (n=5) had 4 or more mutations. The most frequently identified mutations included NRAS (33%, n=17), BRAF V600E (29%, n=15), TP53 (22%, n=11), CDKN2A (10%, n=5), and CTNNB1 (8%, n=4).

In SS type, no mutations were found in 2% of patients (n=1), while 61% of patients (n=28) had only one mutation, 24% (n=11) had 2 mutations, 7% (n=3) had 3 mutations, and 7% (n=3) had 4 or more mutations. The most frequently identified mutations were NRAS (35%, n=16), BRAF V600E (33%, n=15), TP53 (17%, n=8), BRAF V600R (11%, n=5), and PTEN (11%, n=5). There was no significant difference in the molecular profiles between nodular and SS types.

Conclusion:We found that the most frequent mutations in nodular melanomas were NRAS, BRAF V600E, TP53, CDKN2A, and CTNNB1, and the most frequent superficial spreading mutations were NRAS, BRAF V600E, TP53, BRAF V600R, and PTEN. It appeared to be more common to have no mutation in nodular melanoma. Future studies will further identify mutation patterns in MM subtypes and correlate them with treatment response.

26.07 Exon Mutational Analysis for GIST: Dissemination and Impact on Treatment

Posted on January 18, 2018

A. J. Bartholomew1, H. Dohnalek1, P. Prins2, H. S. Quadri3, L. B. Johnson3, N. G. Haddad4, J. L. Marshall2,5, W. B. Al-Refaie2,3,6,7  1Georgetown University Medical Center,School Of Medicine,Washington, DC, USA 2Georgetown University Medical Center,Lombardi Comprehensive Cancer Center, Ruesch Center For The Cure Of Gastrointestinal Cancers,Washington, DC, USA 3Georgetown University Medical Center,Surgery,Washington, DC, USA 4Georgetown University Medical Center,Gastroenterology,Washington, DC, USA 5Georgetown University Medical Center,Hematology/Oncology,Washington, DC, USA 6MedStar-Georgetown Surgical Outcomes Research Center,Washington, DC, USA 7MedStar Health Research Institute,Hyattsville, MD, USA

Introduction:  Tyrosine kinase inhibitors (TKI) have become the guideline-recommended therapy for high-risk resected, recurrent, and metastatic gastrointestinal stromal tumors (GIST). Exon mutational analysis (EMA) is used to inform pre-therapy response to TKI and may predict overall prognosis. Despite these benefits, EMA remains underused, and its impact on TKI therapy decision-making remains unexplored. We sought to better characterize the use of EMA in GIST patients receiving TKI and to quantify the subsequent impact on treatment at a comprehensive cancer center.  

Methods:  A retrospective cohort was established from 104 patients who received treatment for pathologically confirmed, c-KIT-positive and -negative GIST from 2006 to Jan 2017. Variables collected included patient, tumor, and treatment characteristics. According to current National Comprehensive Cancer Network (NCCN) guidelines, EMA should be considered for all patients undergoing TKI therapy to identify genotypes that will, or will not, respond to treatment. We first tracked guideline-considered EMA use in GIST patients who received TKI over time. We then identified how the return of EMA results informed treatment decision-making across the study period. 

Results: Among the 104 GIST patients, 54 (52%) of patients received adjuvant or neoadjuvant TKI. Of these 54 patients, only 22 (41%) received EMA, as considered by NCCN guidelines. The use of EMA varied during our study course (Figure 1). Genotypes identified from EMA included 50% of patients with a mutation in KIT exon 11, 5% with KIT exon 9, 9% with PDGFRA exon 18, and 36% with wildtype GIST. Informed by these EMAs, TKI treatment decisions included 59% who continued on their original TKI regimen, 32% who switched to an alternative TKI treatment, and 9% who discontinued TKI treatment based on primary resistance. 

Conclusion: Less than half of patients receiving TKI therapy for GIST received EMA at a comprehensive cancer center. Despite this low uptake, when it was performed, EMA resulted in an alternative treatment decision in 41% of patients. Future interventions are needed to identify and mitigate barriers responsible for underuse of EMA prior to initiating TKI therapy for GIST. 

 

26.08 Consecutive Case Series of Melanoma Sentinel Node Biopsy for Lymphoseek Compared to Sulfur Colloids

Posted on January 18, 2018

C. Silvestri1, A. Christopher1, C. Intenzo2, J. Kairys1, S. Kim2, A. Willis1, A. C. Berger1  1Sidney Kimmel Medical College At Thomas Jefferson University,Surgery,Philadelphia, PA, USA 2Thomas Jefferson University Hospital,Nuclear Medicine/Radiology,Philadelphia, PA, USA

Introduction:
Sentinel lymph node biopsy (SLNB) is the current standard of care for patients diagnosed with melanoma >1mm. Preoperative lymphoscintigraphy with radiolabeled isotopes is essential to localize sentinel nodes for removal. Our study compared the effectiveness of Lymphoseek to standard sulfur colloids (SC) during lymphoscintigraphy in patients with melanoma undergoing SLNB.

Methods:
We queried our IRB-approved melanoma database at Thomas Jefferson University to identify 370 consecutive patients who underwent SLNB between 2012-2016 and at least one year of follow up. There were 185 patients who underwent SLNB with the standard SC, and 185 patients who underwent SLNB with Lymphoseek. Data points included primary characteristics of the melanoma (primary site, Breslow thickness, ulceration), lymphoscintigraphy (dosage of radiotracer, mapping time), and SLNB (number of sentinel nodes removed, number of positive sentinel nodes, and false negatives). Student’s t-test and Chi-Square were used to analyze the data with a p-value of <0.05 being considered significant.

Results:
Between the two groups, patients were equally matched in regard to age, sex, and primary characteristics of their melanoma including thickness, primary site, and presence of ulceration. In comparison to SC, Lymphoseek required lower radiation dosages (p<0.001), shorter mapping times (p=0.008), and decreased number of sentinel nodes removed (p=0.03). There was no difference in the number of patients with positive nodes (p=0.5). Additionally, there were no statistical differences between the two radioactive tracers in regard to average number of hot spots per basin, or the number of patients with false negative SLNB.

Conclusion:
Lymphoseek has the potential to decrease radioactivity and mapping time in patients who need SLNB. With a decrease in the number of nodes removed without loss of sensitivity, there is a potential to avoid unnecessary node removal and thus complications such as lymphedema. Longer follow-up will help to determine if there is any increase in false negative rates despite fewer nodes removed.
 

26.05 Perioperative Chemotherapy Use for High Grade Truncal Sarcomas May Not Improve Survival

Posted on January 18, 2018

P. Y. Yu1, E. W. Beal1, L. Suarez-Kelly1, R. Shelby1, T. M. Hughes1, C. G. Ethun2, T. B. Tran3, G. Poultsides3, J. Charlson4, T. C. Gamblin4, J. Tseng5, K. K. Roggin5, K. Chouliaras6, K. Votanopoulos6, B. A. Krasnick7, R. C. Fields7, R. E. Pollock1, V. Grignol1, K. Cardona2, J. H. Howard1  1Ohio State University,Columbus, OH, USA 2Emory University School Of Medicine,Atlanta, GA, USA 3Stanford University,Palo Alto, CA, USA 4Medical College Of Wisconsin,Milwaukee, WI, USA 5University Of Chicago,Chicago, IL, USA 6Wake Forest University School Of Medicine,Winston-Salem, NC, USA 7Washington University,St. Louis, MO, USA

Introduction:  The benefit of perioperative chemotherapy (CTX) for treatment of truncal soft-tissue sarcoma (STS) is not well established. Our aim was to determine the effect of CTX on the outcomes of patients with surgically resected primary truncal STS.

Methods:  Adult patients with high grade truncal STS who had primary resection for curative intent from 2000-2016 at 7 U.S. institutions were evaluated retrospectively. Patients with well-differentiated liposarcoma, dermatofibrosarcoma protuberans, desmoid tumors, low-grade sarcomas or palliative resections were excluded. Patients were stratified by receipt of CTX. Categorical variables were compared using chi-square or Fisher exact test. Continuous variables were compared using two-sample t-tests or Mann-Whitney U test. Kaplan-Meier curves with log-rank tests were used to compare overall survival (OS) and recurrence-free survival (RFS). Logistic regression models were used to evaluate characteristics associated with OS.

Results: Of patients with high grade truncal STS, 235 received curative intent resections. The most common histology was undifferentiated pleomorphic sarcoma and mean tumor size was 7.8 cm. Thirty percent of the patients received CTX (n=70): 10% (n=24) neoadjuvant CTX, 13% (n=31) adjuvant CTX and 6% (n=15) neoadjuvant and adjuvant CTX. Patients who received CTX were younger (48 vs 59 yrs, p<0.001), less likely to have hypertension (30% vs 50%, p<0.01), more likely to have deep tumors (86 vs 73%, p<0.05), radical resections (87 vs 72%, p<0.05), chest wall/rib resections (43 vs 24%, p<0.01), solid organ invasion (14 vs 3%, p<0.01), longer operative time (228 vs 142 min, p<0.01) and radiation (51 vs 34%, p<0.05). On univariate analysis patients who received CTX had significantly worse OS (p<0.01) and a trend towards worse RFS (p=0.08) (Fig 1). Margin status was the only variable associated with OS on multivariate analysis (OR 4.36, 95% CI 1.56, 12.13, p<0.01).

Conclusion: In this multi-institutional retrospective analysis of high grade truncal STS undergoing curative resection, microscopically-negative margin status was the only independent factor associated with better survival. The receipt of perioperative CTX was not associated with improved OS which may be explained by selection bias. Treating physicians at high-volume sarcoma centers can predict patients likely to have poor outcomes based on clinical and surgical findings. This results in a higher likelihood to administer CTX to patients with worse tumor biology. Our findings emphasize the importance of margin-negative resection as the foundation of optimal sarcoma treatment as well as the need for a better biologic understanding of truncal STS to help guide clinical decision making.

26.06 Preoperative Immunonutrition for Axillary or Inguinal Lymphadenectomy: Tolerability and Outcomes.

Posted on January 18, 2018

D. B. Porter1, K. M. McMasters1, C. R. Scoggins1, R. C. Martin1, M. E. Egger1, P. Philips1  1University Of Louisville,Louisville, KY, USA

Introduction:
Axillary and inguinal lymphadenectomy for melanoma is associated with a high infectious complication rate and lymphedema. There are conflicting data on the efficacy of preoperative immunonutritional supplementation in reducing infectious complication rates mostly after abdominal surgery. The aim of this study is to assess the tolerability and efficacy of preoperative immunonutrition in reducing infectious complications after inguinal and axillary lymphadenectomy.

Methods:
Thirty-nine patients who underwent inguinal/axillary lymphadenectomy for melanoma, between 2014-2017, received 5 days of immunonutritional supplement (3 cans of Impact AR®, Nestle® containing arginine, omega-3 fatty acids, nucleotides) preoperatively and perioperative outcomes were compared with thirty-nine patients from 2011-2017 who did not receive nutritional supplementation from a prospective melanoma database. All patients underwent nutritional assessment using the MUST (Malnutrition Universal Screening Tool) score and malnourished patients (score >1) were excluded from this study.  High-grade infectious complications were defined as infections requiring intervention or hospitalization (CTCAE V4.03, Grade 3 or higher). 

Results:
Immunonutrition group and control group had similar comorbidities (diabetes: 6 vs. 7, p=0.6572, tobacco use: 15 vs. 15), primary site (truncal 18 vs. 19, extremity 21 vs. 20, p=0.748) and lymphadenectomy site (groin 16, axillary 23 each). Median lymph node yields were similar between both groups for axillary (19, IQR 13, 23.5 vs. 18, IQR 13.5, 23.5, p=0.872) and inguinal lymphadenectomy (15 IQR 10, 21 vs. 15, IQR 11.5, 20, p=0.853). Overall compliance was good with 31 (79.5%) patients completing the 5-day course and 8 (20.5%) completing at least 3 days. Reasons for poor compliance were dislike of the supplement flavor in 5 and bloating in 4. No significant difference was noted between the two groups with respect to postoperative seroma rate, prolonged drainage, length of hospital stay and lymphedema rates. Overall complication rates were similar (19, 48.7% vs. 24, 61.5%, p=0.2513) but the immunonutrition group had a lower total number of patients with infectious complications (7 vs. 14, p=0.0035) and fewer high-grade infections (3 vs. 8, p=0.0027). 

Conclusion:
Preoperative immunonutrition with Impact AR® was well tolerated and in well-nourished patients demonstrated a significant decrease in infectious complications. A larger randomized trial is needed to further investigate this finding. 
 

26.04 The Prognostic Significance of Tumor-Infiltrating Lymphocytes for Primary Melanoma Varies by Gender

Posted on January 18, 2018

A. J. Sinnamon1, C. E. Sharon1, Y. Song1, M. G. Neuwirth1, D. E. Elder2, X. Xu2, D. L. Fraker1, P. A. Gimotty3, G. C. Karakousis1  1Hospital Of The University Of Pennsylvania,Endocrine And Oncologic Surgery,Philadelphia, PA, USA 2Hospital Of The University Of Pennsylvania,Pathology,Philadelphia, PA, USA 3University Of Pennsylvania,Biostatistics, Epidemiology And Informatics,Philadelphia, PA, USA

Introduction:
The immune response to melanoma, manifested locally by tumor-infiltrating lymphocytes (TILs), has gained increasing attention in the era of effective immunotherapies. Men and women are known to have varying patterns of immunity, yet gender-specific prognostic implications of TILs have not been explored.

Methods:
Patients with clinically localized primary melanoma ≥0.76mm who underwent sentinel lymph node (SLN) biopsy were identified within our institutional melanoma database. Association between TILs (categorized as absent, nonbrisk, and brisk) and SLN positivity was evaluated using logistic regression. The possibility of interaction between gender and TILs on the rate of SLN positivity was assessed using the Wald test. Overall survival estimates were obtained using the Kaplan-Meier method and Cox regression with separate analyses performed by gender.

Results:
Among 1,367 patients identified, 794 (58%) were men. TILs were brisk in 143 (10%) lesions, nonbrisk in 903 (66%), and absent in 321 (23%); this distribution did not vary by gender (p=0.71). Among men, SLN positivity rate was significantly associated with TILs (brisk 3.8%, nonbrisk 16.9%, absent 26.6%, p<0.001). In contrast, there was no significant relationship between TILs and SLN status in women (see figure; p=0.49). Significant interaction between brisk TILs and female gender on SLN status was identified (p=0.029). This interaction remained significant in multivariable analysis adjusting for clinicopathologic factors (p=0.043). Among men, presence of brisk TILs was associated with prolonged overall survival (brisk HR 0.43, p=0.038; nonbrisk HR 0.84, p=0.34). This association was no longer significant after adjustment for SLN status (brisk HR 0.72, p=0.42; nonbrisk HR 1.05, p=0.79). In contrast, no association between TILs status and overall survival was observed among women (brisk HR 0.97, p=0.95; nonbrisk HR 1.06, p=0.85).

Conclusion:
The negative prognostic implications of absent TILs on SLN status and thus on survival appear to be stronger among men than women. This may provide some basis for better melanoma-specific prognosis among women.

25.10 Thrombospondin Induced Protein Expression Correlates with Gene Expression Linked to Arterial Disease

Posted on January 18, 2018

M. M. Kassem1,2, D. Brusch1,2, K. G. Maier1,2, V. Gahtan1,2  1State University Of New York Upstate Medical University,Vascular And Endovascular Services,Syracuse, NY, USA 2Syracuse VA Medical Center,Syracuse, NY, USA

Introduction:  Thrombospondins (TSPs) are matricellular glycoproteins expressed in response to vascular injury and are mediators of arterial remodeling. While TSP-1 and TSP-2 induce vascular smooth muscle cell (VSMC) proliferation, TSP-5 does not. However, all three TSPs promote VSMC migration.  Previously we showed that TSP-1,-2 and -5 alter gene expression associated with arterial remodeling in VSMCs. The current study assesses the expression of these genes at the protein level. Our previous work has shown TSP-1, -2 and -5 all downregulate IL-8 gene expression while they increase ANGPTL-4 gene expression. Furthermore, both TSP-1 and -2 upregulate the PDGF-BB gene, while only TSP-1 increased TGF β1 gene expression. We hypothesized that protein expression of by all three TSPs would mirror the effects on the genes in VSMCs.  

Methods:  Quiescent Human VSMCs were exposed to TSP-1,-2 or -5 (20 μg/ml) or serum free media (SFM), for 24 hours. Cell lysates were used to determine TSP-1, -2 and -5 expression.  The culture media was used to detect secreted proteins (TGF-β1, PDGF-BB, ANGPTL-4, IL-8). TSP-1, -2, -5 and ANGPTL-4 protein expression were measured by Western blot. IL-8, PDGF-BB and TGF-β1 protein secretion were determined by ELISA. Statistical analysis was performed by ANOVA and t-test. P< 0.05 was considered significant. 

Results:  The table lists proteins for each treatment as upregulated, downregulated or went from undetectable to detectable. TSP-2 was found to be a significant self-promoter and it upregulates ANGPTL-4 25 fold. While the effect of TSP-1 on autoregulation was inconclusive, TSP-1 upregulates secretion of ANGPTL-4, PDGF-BB and TGF-β1. TSP-5 wasn’t detected in TSP-1, -2 and SFM treated cells.

Conclusion:  Substantial differences exist in VSMC protein expression patterns following exposure to the thrombospondins. This study confirms our previous gene expression data in VSMCs treated with TSP-1,-2 and -5. These findings suggest that TSP-1 promotes vascular remodeling, in part, by increasing ANGPTL-4, PDGF-BB and TGF-β1 secretion. Additionally, TSP-2 upregulates TSP-1 and -2 expression and increases secretion of PDGF-BB and ANGPTL-4.  TSP-5 may be protective against arterial remodeling as it up regulates its own expression and does not upregulate PDGF-BB.  These findings increase our understanding of the mechanisms by which TSPs differentially regulate VSMC function.

26.02 Tumor Mitotic Rate: A Strong, Independent Predictor of Survival for Localized Melanoma

Posted on January 18, 2018

J. L. Evans1, R. J. Vidri1,2, D. C. MacGillivray1, T. L. Fitzgerald1  1Tufts University School Of Medicine – Maine Medical Center,Surgery,Portland, ME, USA 2St. Mary’s Regional Medical Center,Surgery,Lewiston, ME, USA

Introduction:
The prognostic significance of tumor mitotic rate (TMR) for patients with localized melanoma has engendered significant controversy. Although several small studies have validated TMR as a prognostic marker for this disease, TMR is no longer incorporated in the AJCC staging paradigm. To better define TMR as an independent predictor of disease-specific survival for localized melanoma, we performed a cohort study utilizing an administrative cancer database.

Methods:
Patients diagnosed with localized cutaneous melanoma from 2010 to 2014 were identified from the SEER registry. TMR was then categorized into three groups based on the number of mitoses:  0-3 mitoses/mm2 (Group 1), 4-10 mitoses/mm2 (Group 2), and >10 mitoses/mm2 (Group 3). Five-year disease-specific survival for stage and TMR category were calculated using the Kaplan-Meier method, groups were compared using the log-rank test. Multivariate analysis was performed using Cox proportional hazards model. (Using JMP 13. Cary, NC: SAS Institute Inc.)

Results:
A total of 71,235 patients were included; the majority were white (94.7%), male (58.5%), and had Stage I disease (79.0%). When analyzed both as a categorical and a continuous variable, TMR was associated with disease-specific survival for all TNM stages.   Univariate analysis demonstrated that 5-year disease-specific survival decreased with increasing TMR in Groups 1, 2, and 3 for Stage I (98.31%, 90.90%, 79.74%; p<0.0001), Stage II (86.07%, 74.17%, 72.85%; p<0.0001), and Stage III melanoma (72.52%, 58.58%, 49.65%, p<0.0001).  Multivariate analysis controlling for age, race, sex, primary site, ulceration, and Breslow thickness revealed an increased mortality risk for those melanoma with 4-10 mitosis/mm2 and more than 10 mitosis/mm2, when compared to those with 0-3 mitosis/mm2: Stage I (RR=3.00 and 6.90 p<0.0001), Stage II (RR=1.37 and 1.63, p=0.0002), and Stage III disease (RR=1.33 and 1.46 p=0.0004).  When analyzed as a continuous variable in this model, each unit increase in TMR increased the risk of death by 22% in Stage I (p<0.0001), 5% in Stage II (p<0.0001), and 4% in Stage III melanoma (p<0.0001).

Conclusion:
This retrospective cohort study, the largest to date; suggests that tumor mitotic rate is a strong, and independent predictor of disease-specific survival in melanoma. While the literature has previously demonstrated the prognostic value of TMR in Stage I disease, the present study expands upon this knowledge by demonstrating a similar relationship in Stage II and III melanoma.
 

26.03 A Multi-institutional Analysis of Elderly Patients Undergoing Resection for Retroperitoneal Sarcomas.

Posted on January 18, 2018

K. H. Wilkinson1, C. G. Ethun2, M. Hembrook1, M. Bedi5, J. Charlson4, H. Mogal1, K. K. Christians1, T. B. Tran3, G. Poultsides3, V. Grignol6, J. H. Howard6, J. Tseng7, K. K. Roggin7, K. Chouliaras8, K. Votanopoulos8, D. Cullinan9, R. C. Fields9, S. Weber10, T. C. Gamblin1, K. Cardona2, C. N. Clarke1  1Medical College Of Wisconsin,Division Of Surgical Oncology,Milwaukee, WI, USA 2Winship Cancer Institute, Emory University,Department Of Surgery,Atlanta, GA, USA 3Stanford University,Department Of Surgery,Palo Alto, CA, USA 4Medical College Of Wisconsin,Department Of Medical Oncology,Milawuakee, WI, USA 5Medical College Of Wisconsin,Department Of Radiation Oncology,Milwaukee, WI, USA 6The Ohio State University,Department Of Surgery,Columbus, OH, USA 7University Of Chicago,Department Of Surgery,Chicago, IL, USA 8Wake Forest University,Department Of Surgery,Winston-Salem, NC, USA 9Washington University,Department Of Surgery,St. Louis, MO, USA 10University Of Wisconsin,Department Of Surgery,Madision, WI, USA

Introduction: Little is known about the postoperative outcomes of elderly (≥70yrs) patients undergoing radical resection of retroperitoneal sarcomas (RPS).  We hypothesize that biological age impacts outcomes and prognosis after surgical resection in patients with RPS.

Methods: Three hundred and nine patients undergoing surgical resection for primary or recurrent RPS between 2000 and 2015 at participating US Sarcoma Collaborative institutions were identified. Patient demographics, perioperative morbidity, mortality, length of stay (LOS), discharge to home, disease specific survival (DSS) and disease free-survival (DFS) were compared between elderly (≥70yrs, n=69) and non-elderly (<70yrs, n= 240) patients.

Results: Median age at time of surgery for  elderly and non-elderly patients was 76yrs (IQR=7) and 55yrs (IQR=18), respectively . Elderly patients had a median ASA of 3 (IQR =1) while non-elderly had a median of 2 (IQR =1). Median tumor size was larger in the elderly group (12 cm [IQR=15] vs. 9 cm [IQR=8], p =0.004). There was no difference in median operative time (183 mins [IQR 114] vs. 214 mins [IQR 191], p= 0.06) or estimated blood loss (300 mL [IQR 650] vs. 300mL [IQR 900], p= 0.22) between elderly and non-elderly patients. Thirty-two (39%) elderly patients underwent bowel resection, 7 (8.5%) nephrectomy, 4 (4.9%) pancreatic resection, 2 (2.9%) liver resection, and 3 (4.3%) major vascular resection. Incidence of total and major complications was comparable between groups (elderly vs. non-elderly: 42.0% vs. 38.8%; p = 0.62 and 24.6% vs. 20.0%; p = 0.41).  LOS was similar with a median of 8 days (IQR 6) in the elderly group and 6 days (IQR 5) in the non-elderly group, p= 0.64. There was no difference in 30-day readmission rates between elderly and non-elderly patients (11.6% and 10.8%, p= 0.86). 61 (88.4%) elderly patients were discharged to home, 2 (2.9%) to subacute rehab facilities and 5 (7.2%) to skilled nursing facilities. Perioperative mortality was comparable in both groups (elderly vs. non-elderly, 0% vs 0.2% p= 0.28). There was no difference in three-year DFS between the elderly and non-elderly patients (18.8% vs 21.6% p=0.61) however elderly patients had lower three-year DSS (25.1% vs 56.1% p< 0.001) (Figure).

Conclusion: Elderly patients undergoing resection for retroperitoneal sarcoma at high-volume academic centers demonstrated analogous perioperative morbidity and mortality when compared to their younger counterparts. Three-year DFS was similar between groups however, elderly patients are more likely to die from their disease after recurrence as evidenced by lower DSS compared with younger patients.

 

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