78.04 Vitamin C And Nitric Oxide: A Synergistic Effect On Colonic Crypts

Posted on January 26, 2017

C. N. Vanicek1, M. M. Aldajani1, N. Alhazzaa1, R. Agarwal1, J. P. Geibel1  1Yale University School Of Medicine,Surgery,New Haven, CT, USA

Introduction:

For colorectal cancer to grow and invade healthy tissues, it must maintain a higher (more alkali) intracellular pH and a lower (more acidic) extracellular pH, in the immediate environment around the metaplastic cell. For this reason, colorectal cancer remains as one of the leading causes of death in the United States and worldwide.

In a study presented at this meeting we provide evidence that acute Vitamin C exposure at high doses could down regulate Na-dependent acid efflux pathways in colonic crypt cells. In previous studies, Vitamin C was shown to increase nitric oxide production through stimulating nitric oxide synthase. The role of nitric oxide (NO) on cancer growth remains complex. Prolonged chronic exposure to NO ,which is typical during chronic inflammation, leads to gene mutations which were linked to cancer development. However, conversely it also has been shown that NO derived from macrophages, Kupffer cells, natural killer cells, and endothelial cells is a tumorcidal agent that results in cancer apoptosis and cessation of growth and metastasis. In this present study we examined the acute effects of Vitamin C exposure on nitric oxide

production and its effects on Na-dependent acid secretion.

Methods:

Following excision, rat colon was digested leaving single isolated crypts, which were then

incubated with the pH sensitive dye BCECF. The crypts were then imaged while being perfused

with solutions either containing or devoid of Vitamin C, L-NAME and L-Arginine. The ratio image

data was collected every 10 second. to allow a direct real time measurement of changes in pH All

data were then analyzed with GraphPad Prism.

 

 

Results:

By comparing rates of pH recovery under these various conditions we found that: 1) There was no difference in the Na-dependent H extrusion rate between Vitamin C and L-arginine. 2) Treatment of colonic crypts with L-NAME, a NO synthesis inhibitor, reversed the Vitamin C dependent NHE inhibition.

Conclusion:

We found that exposure to Vitamin C gives a similar inhibition in acid secretion as Arginine a known NO producer. This further shows a tight link to Vitamin C and NO production and the ability of NO to significantly inhibit hydrogen ion excretion. In separate studies where crypts were given L-NAME the level of acid secretion returned to normal control rates. Our data suggest a tight link between Vitamin C exposure and a reduction of acid secretion via NO synthesis. Therefor the anti-tumorigenic effect equated to Vitamin C may be synergistic with the tumorcidal effect of NO found in other tissues.

78.03 NIR-Conjugated Humanized Anti-CEA Antibody to Target Colon Cancer in an Orthotopic Nude Mouse Model

Posted on January 26, 2017

J. C. DeLong1, T. Murakami1,2, P. J. Yazaki3, R. M. Hoffman1,2, M. Bouvet1  1University Of California – San Diego,Surgery,San Diego, CA, USA 2AntiCancer, Inc.,San Diego, CA, USA 3City Of Hope National Medical Center,Immunology,Duarte, CA, USA

Introduction:  The success of a curative surgery for cancer is dependent on the complete removal of all cancer cells, an R0 resection. Intraoperative verification of clear tumor margins is not possible by the surgeon and requires a surgical pathologist to analyze frozen sections of the resected tumor. Tumor visualization by the surgeon can be enhanced through fluorescence-guided surgery (FGS) by delivering labeled tumor-specific antibodies. We selected humanized anti-carcinoembryonic antigen (CEA) conjugated to a near-infrared (NIR) dye to target orthotopically implanted human colon cancer in nude mice.

Methods:  The HT-29 cell line for human colon cancer was grown in culture and subcutaneously injected subcutaneously in a nude mouse model. After 3 weeks of growth tumors were resected and cut into 2 mm3 fragments that were sutured to the cecum of 5 additional nude mice. The tumors were allowed to grow for 4 weeks at which point 3 had successful orthotopic tumor growth and were selected for injection of the humanized antibody for CEA that was convalently bound to the IR800 NIR dye (anti-CEA-IR800) through an ester reaction. Antibody-dye conjugate (75 μg ) was intravenously administered via tail vein injection. Images were taken with the Pearl Trilogy Small Animal Imaging System (Li-Cor, Lincoln, NE) pre-injection, 5 min post, 5 hours post, 24 hours post (with laparotomy views), and 48 hours post injection (with laparotomy views) with both 700 nm and 800 nm channels. Images were evaluated using Image Studio.

Results: Images taken at 5 min and 5 hours (through skin, no laparotomy) did not demonstrate appreciable accumulation in the tumor. At 24 hours laparotomy was performed and the tumors were strongly labeled with anti-CEA-IR800 when imaged through the 800 nm channel. At 48 hours laparotomy was repeated which again demonstrated strong labeling of the tumors through the 800 nm channel, but with a lower absolute intensity (in relative units), than at 24 hours for each of the 3 mice imaged. Normal bowel was fluorescent through the 700 nm channel due to the autofluorescence of plant chlorophylls in mouse chow.

Conclusion: Humanized anti-CEA-IR800 can rapidly and effectively label CEA-expressing human colon cancer in an orthotopic nude mouse model. Given the ability of this technology to target and label tumor with great specificity, anti-CEA-IR800 should be made available for clinical use for fluorescence guided surgery in the near future.

78.02 Altered Microbiome in Pancreatic Cancer and Chronic Pancreatitis

Posted on January 26, 2017

M. A. Mederos1, A. McElhany1, J. Petrosino2, N. J. Ajami2, N. Villafane1, S. Mohammed1, E. Oliva1, W. E. Fisher1, G. Van Buren1  1Baylor College Of Medicine,Department Of Surgery, Division Of Surgical Oncology,Houston, TX, USA 2Baylor College Of Medicine,Department Of Molecular Virology And Microbiology,Houston, TX, USA

Introduction:  Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease that lacks a method of early detection. Established risk factors for PDAC suggest an inflammatory mechanism of carcinogenesis. Recent epidemiological data portends that certain bacterial populations may increase PDAC susceptibility & progression by diverse mechanisms including modulating inflammation. We aim to characterize the microbiome of pancreatic tissue in those with PDAC & chronic pancreatitis (CP).

Methods:  Patients who underwent pancreas resection at our institution from 2004-2016 were identified from our database. Baseline demographics, co-morbid conditions, clinical characteristics, & outcome data were obtained from review of the database. In this cross-sectional study, we used next-generation sequencing protocols & high throughput 16S rRNA gene sequencing to characterize the microbiota in CP/PDAC & normal-adjacent tissue samples (n=6 matched pairs). Shannon diversity indices were used to compare taxonomic richness. Beta-diversity distance comparison was used to compare compositional differences between the two patient groups. P values were calculated using a Wilcoxon matched-pairs rank test & Kruskal-Wallis statistical tests with false discovery rate correction.

Results: Baseline demographics were similar between patient groups. Analysis shows that the microbiome in PDAC & CP tissue samples is dominated by species of lipopolysaccharide (LPS)-rich Proteobacteria followed by Firmicutes, Bacteroidetes, & Actinobacteria with relative abundance means of 53.65%, 31.55%, 5.56%, & 5.04%, respectively. We also observed lower bacterial richness in tumor-associated samples compared to normal-adjacent (p=0.65). This finding was accompanied by an overall increase of LPS-rich Enterobacter species in PDAC tissue compared to normal tissue (p=0.094).

Conclusion: Our analysis showed a dominance of LPS-rich Proteobacteria & a trend to lower microbial richness. Low microbial richness suggests the dominance of a single or few bacteria — a hallmark of microbe-induced inflammatory processes. The trend toward decreased diversity is possibly a result of a multi-factorial dysbiotic state & probably contributes to the pathogenesis of PDAC. Recent studies suggest a role for Proteobacteria in carcinogenesis through inflammatory processes mediated by TLR-activating molecules such as LPS.  There is an inherent basal diversity in the microbial structure across multiple body sites due to environmental & genetic factors, thus more specimens are needed to correlate microbial patterns with clinical outcomes. Further studies with more specimens are needed to detect a statistical difference of the microbiome between matched tissue pairs.

78.01 Comparison of pH­sensitive fluorescent nanoprobe to cetuximab­IRDye800 for realtime imaging of SCC

Posted on January 26, 2017

M. Tabata1, N. Nathan1, T. Teraphongphom1, K. Hettie2, J. Klockow2, S. Rogalla3, R. Ertsey1, E. Rosenthal1,2  2Stanford University,Radiology,Stanford, CA, USA 3Stanford University,Pediatrics,Palo Alto, CA, USA 1Stanford University,Otolaryngology – Head And Neck Cancer,Palo Alto, CA, USA

Introduction: Despite widespread acceptance of fluorescence imaging for several different types of cancer, the ideal optical imaging probe for intraoperative delineation of head and neck squamous cell carcinoma (HNSCC) margins has not yet been identified. Identification of this probe for detecting subclinical disease in tumor margins will improve oncologic surgical outcomes. This study compares a fluorescently labeled anti-­epidermal growth factor receptor (EGFR) antibody, Cetuximab-­IRDye800CW (IR800-CTM), with an ultra pH­-sensitive (UPS) fluorescent nanoprobe for detection of HNSCC.

Methods: Thirteen immunodeficient mice were inoculated with HCT. Through tail vein injections, four mice were given 200 uL of IR800-CTM at 14uM. Three were given 100 uL of UPS nanoprobes, and three were given 200 uL, both at 0.1 mg/mL. Two were given 200 uL of saline, and one was given 200 uL of IRDye800 at 28uM. Images were acquired using the Pearl® Trilogy(LI-COR) in vivo optical imaging system at 8, 22, 26, 30, 46, and 72 hours along with the SPY Elite®(Novadaq) at 72 hours. Ex vivo images were acquired using the Pearl® and Odyssey®(LI-COR). Tumor­ to ­background ratios (TBR) were calculated by dividing the intensity of the fluorescence in the tumor by that of healthy flank tissue. TBRs of the UPS nanoprobe group and the IR800-CTM group were compared. An unpaired, two-­sided Student’s T-­test with unequal variance was used to test for statistical significance.

Results: There is no statistically significant difference between TBRs of UPS nanoprobes and IR800-CTM in vivo. We can successfully image tumors in vivo and obtain TBRs of 2.81 (±0.68 SD) with UPS nanoprobes and 5.27 (±1.85 SD) with IR800-CTM. Ex vivo histology confirms fluorescence in tumors. The TBR of the UPS nanoprobes reached a maximum at 22 hours and stayed above 83% of maximum until 72 hours. The lower dose of 100µL yields stronger and more specific signal than the 200µL dose. Both UPS nanoprobes and IR800-CTM localize in kidneys and liver, and IR800-CTM shows greater tumor:liver fluorescence ratio.

Conclusion: Both UPS nanoprobes and IR800-CTM are tools for intraoperative optical visualization of cancer. The earlier TBR peak of UPS nanoprobes is clinically advantageous. Currently, complete removal of HNSCC with minimal damage to other tissues cannot be guaranteed, and improved visualization of tumor margins would improve post-­surgery oncologic outcomes. We compare two methods for optical imaging of tumor margins in HNSCC. These outcomes will help guide further investigation of an optimal optical imaging agent for HNSCC. This methodology is reproducible for investigation in other tumor types.

77.05 Not all Readmissions are Created Equal – Index vs. Non-Index Readmissions After Major Cancer Surgery

Posted on January 26, 2017

S. Zafar1, A. A. Shah1, H. Channa2, L. L. Wilson4, N. Wasif3  1Howard University College Of Medicine,General Surgery,Washington, DC, USA 2Purdue University,Agricultural Economics,West Lafayette, IN, USA 3Mayo Clinic In Arizona,Surgical Oncology,Phoenix, AZ, USA 4Howard University College Of Medicine,Surgical Oncology,Washington, DC, USA

Introduction:
Hospital readmissions after major cancer surgery pose a major healthcare burden and are associated with increased costs and worse outcomes. Increasing regionalization of cancer surgery has the inadvertent potential to lead to fragmentation of care if readmissions occur at a different hospital from the index facility.  Using a national dataset we aim to quantify rates of readmission to non-index hospitals after major cancer surgery and to compare outcomes between index and non-index hospital readmissions.

Methods:
We used the National Readmissions Dataset (2013) as our data source. All adult patients undergoing a major cancer operation (defined as esophagectomies/gastrectomies, hepatico-biliary resections, pancreatectomies, colorectal resections, and cystectomies) within the first 9 months of the year were selected. Readmission characteristics including timing, cost, morbidity and mortality were analyzed. Discharge weights were used to calculate national estimates. Adjusting for clustering by facility, we used multivariate logistic regression to identify factors associated with non-index vs. index readmissions and also to identify differences in mortality, major complications and subsequent readmissions.  Generalized linear modeling was used to test for differences in length of stay (LOS) and hospital costs between the two groups.

Results:
A total of 57,362 patients with 86,362 hospital admissions were analyzed. Overall, the 90 day readmission rate was 23.1% and median time to readmission was 42 days (IQR 20-70 days). Weighted analysis revealed the total national cost for 90 day readmissions to be $682 million. Of the 17,020 readmissions, 22.0% were to a non-index hospital. Independent factors associated with 90 day readmission to a non-index hospital included younger age,  male gender, type of procedure, more comorbidities, Medicaid insurance, longer LOS, in-hospital complications, discharge to a nursing facility, and index surgery at a teaching hospital (p<0.05).  Following risk adjustment, patients readmitted to non-index hospitals had 32% higher odds of mortality (OR 1.32, 95% CI: 1.03-1.70) and 26% higher odds of having a major complication (OR 1.26, 95% CI: 1.10-1.43). Subsequent readmissions and hospital costs were not significantly different between the two groups.

Conclusion:
The 90 day readmission rate following major cancer surgery in the United States is 23.1%, of which a further 22% are to a non-index hospital. When compared to patients readmitted to the index hospital, readmission to a non-index hospital is associated with higher mortality and morbidity. Targeted interventions to reduce non-index readmissions may mitigate fragmentation of postoperative care and result in improved outcomes.
 

68.10 Surgical Experience and the Practice of Pancreatoduodenectomy

Posted on January 26, 2017

G. T. Kennedy1, M. T. McMillan1, M. Sprys1, J. A. Drebin1, C. M. Vollmer1  1Hospital Of The University Of Pennsylvania,Philadelphia, PA, USA

Background:  Surgeons with greater experience have demonstrated improved outcomes following pancreatoduodenectomy (PD), but little is known about what distinguishes their practice. Furthermore, the concept of experience has been variably interpreted in the surgical literature—some authors prioritize years in practice while others delineate cumulative career procedure volume or annual practice productivity. We sought to identify how these various forms of surgical experience influence management decisions for PD.

 

Methods: A survey assessing PD experience and practice patterns of pancreatic surgeons was distributed by six international gastrointestinal surgical societies. Questions regarding the practice patterns of individual surgeons were presented using a modified Likert scale. Multivariable, stepwise logistic regression analysis identified factors associated with three different forms of experience: years in practice, surpassing the PD learning curve (≥50 PDs), and high annual PD volume (≥25 PD/year).

 

Results: The median career PD volume of the 861 respondents was 80 (Interquartile range: 30-200). With regard to years in practice, forty-four percent of the surgeons were early-career (≤10 years of practice following training), 30% mid-career (11-20 years), and 26% senior-career (>20 years). Senior surgeons were more likely to use pancreatogastrostomy, dunking/invagination, external stents (all P<0.05). In terms of career total volume, the PD learning curve was surpassed by only 65% of respondents. Fewer early-career surgeons (39%) have attained this threshold compared with mid-career (80%) and senior-career (89%) surgeons (P<0.00001). Regression analysis identified factors independently associated with surpassing this learning curve of ≥50 cases (Table). Regarding annual productivity, surgeons in the upper quartile of annual PD volume (≥25/year) also demonstrated certain practice patterns; they were more likely to use the isolated roux limb technique (P=0.044) and the same type of pancreatico-enteric reconstruction on every case (P=0.016), but less likely to use autologous tissue patches (P=0.003) and multiple drains (P=0.0002).

 

Conclusion: The concept of experience in pancreatoduodenectomy encompasses several components: years of practice, attainment of the learning curve, and annual productivity. Each of these notions appear to influence decision-making during this complex operation in different ways. 

68.09 Guideline Adherence in Screening Mammography: Behavior Patterns in Commercially-Insured U.S. Women

Posted on January 26, 2017

J. Yu1, N. P. Carlsson1, G. A. Colditz1, M. S. Goodman1, S. Chang1, J. A. Margenthaler1  1Washington University,Surgery,St. Louis, MO, USA

Introduction:
Over 2 million women currently live with breast cancer in the United States, and the annual incidence of more than 200,000 new cases is predicted to remain constant.  Secondary prevention of breast cancer with screening mammography has become the standard of care, but recent updates in recommended screening mammography frequencies have ignited substantial controversy both among physicians and from a societal perspective.  To better understand the potential impact on patients, we assess guideline adherence in a retrospective cohort of commercially-insured U.S. women diagnosed with breast cancer.

Methods:
Using the Truven Health Analytics|MarketScan®|Database from 2006-2012, we conducted a retrospective review of screening mammography frequencies in women aged 40-60 during the 5 years prior to primary breast cancer diagnosis, excluding ductal carcinoma in situ (DCIS), in 2011-2012.  Patient demographics, family history, and clinical characteristics were extracted from the database, and screening adherence was defined as annual (<14 months) and biennial (<26 months).  Unadjusted and multivariable analyses were performed, with two-sided statistical testing. Statistical significance was determined using α =0.05.

Results:
Of 1,876 women diagnosed with breast cancer in 2011-2012, mean age at diagnosis was 53.7±4.3 years, and patients underwent an average of 5.2±2.4 mammograms (2.7±1.7 screening, 2.0±1.4 diagnostic) prior to diagnosis.  Only 16.4% were adherent to annual screening vs. 51.6% adherent to at least biennial screening.  In the adjusted multivariable analysis, odds of adherence to either annual or biennial screening were significantly increased with family history of breast cancer (OR=1.74 [95% CI=1.30-2.32]; OR=1.50, [95% CI=1.19-1.89]), decreased with higher Klabunde Charlson comorbidity score (OR=0.89 [95% CI=0.82-0.97]; OR=0.92 [95% CI=0.87-0.97]), and unaffected by insurance provider (OR=0.77 [95% CI=0.57-1.0]; OR=1.14 [95% CI=0.91-1.43]) or geographic region (OR=0.98 [95%CI=0.68-1.40]; OR=1.08 [95% CI=0.82-1.42]).

Conclusion:
Biennial screening mammography recommendations will likely result in higher rates of guideline adherence.  In this retrospective cohort, more than triple the number of women included were adherent to biennial vs. annual screening; even so, nearly 50% of commercially-insured U.S. women diagnosed with breast cancer in 2011-2012 were not adherent to even biennial screening prior to diagnosis.  Further assessments of resource utilization and long-term outcomes will be critical to determine appropriate population health intervention methods to increase screening compliance.
 

68.08 Survival In Breast Cancer Associated With Drug Sensitive Or Resistant-related MiRNAs Using TCGA

Posted on January 26, 2017

J. S. Young1, T. Kawaguchi1, L. Yan2, Q. Qi2, S. Liu2, K. Takabe1  1Roswell Park Cancer Institute,Department Of Surgical Oncology,Buffalo, NEW YORK, USA 2Roswell Park Cancer Institute,Department Of Biostatistics And Bioinformatics,Buffalo, NEW YORK, USA

Introduction: MicroRNAs (miRNAs) are short (19-25 nucleotides) noncoding RNAs, which have been discovered to exert function through the degradation or inhibition of mRNA translation. Dysregulation of miRNAs has been identified to play a critical role in carcinogenesis and breast cancer progression. Some miRNAs are reported to be associated with drug sensitivity, while others are associated with drug resistance. In this study, several miRNAs known to be related to the sensitivity or resistance of different breast cancer drug treatments were evaluated for association with overall survival using The Cancer Genome Atlas (TCGA).  This included miR-221/222 related to tamoxifen (TAM), miR-30a related to Taxol/doxorubicin (TAX/DOX), miR-210 related to trastuzumab, miR-342 related to tamoxifen, miR-328 related to mitoxantrone, miR-326 related to VP-16/doxorubicin/MIT, miR-487a related to MIT, and miR-31 related to staurosporine/DOX.

Methods: All clinical datasets were obtained from The Cancer Genome Atlas (TCGA). MiRNA-seq data were retrieved from the GDC data portal to evaluate known drug resistance or sensitivity-related miRNAs (miR-221/222, miR-30a, miR-210, miR-342, miR-328, miR-326, miR-487a, and miR-31) and correlate them clinically to survival. Patients were separated into groups based on high and low expression of miRNA-specific thresholds and survival plots were generated using a Cox proportional hazard model.

Results: Among the 1097 breast cancer cases logged in TCGA, 1053 cases were found to contain appropriate data for analysis. Patients with high expression levels of miR-342, reported to be related to TAM sensitivity, have  increased overall survival (p=0.035). Patients with high expression levels of miR-30a, reported to be associated with TAX/DOX sensitivity, have significant increased overall survival (p=0.032). Patients with high expression levels of miR-31, reported to be associated with staurosporine/DOX sensitivity, have significant increased overall survival (p=0.038) as well. However, miR-328, miR-326, miR-487a, and miR-210 have previously been reported to have some association with increased response to chemotherapy.  In our analysis using TCGA data, they did not show any significant association with overall survival. Surprisingly, high expression levels of miR-221 and miR-222, thought to be related to TAM resistance, demonstrated significant increased overall survival (p=0.047, 0.032, respectively).

Conclusion: Although the role of miRNAs is important in drug sensitivity and resistance, its impact on survival should be validated using large clinical databases such as TCGA.
 

68.07 The validity of omega-3 fatty acids for patients on chemotherapy for biliary or pancreatic cancer.

Posted on January 26, 2017

K. Abe1, T. Uwagawa1, Y. Nakaseko1, K. Haruki1, Y. Takano1, S. Onda1, F. Suzuki1, M. Matsumoto1, T. Sakamoto1, T. Gocho1, S. Wakiyama1, Y. Ishida1, K. Yanaga1  1The Jikei University School Of Medicine,Department Of Surgery,Minato-ku, TOKYO, Japan

Introduction: Previous studies have reported that omega-3 fatty acids inhibit the production of inflammatory cytokines, which show positive impact on several cancer-related cachexia. However, such studies are rarely reported in biliary or pancreatic cancer. Since patients with pancreatic cancer often suffer from exocrine pancreatic insufficiency, the ingestion of omega-3 fatty acids with digestive enzyme supplements may improve nutritional state of such patients. In this study, we prospectively investigated the efficacy of nutritional support by omega-3 fatty acids for the patients receiving chemotherapy for unresectable biliary or pancreatic cancer, and addition of by pancreatic digestive enzyme for pancreatic cancer patients.

Methods: Patients who underwent chemotherapy for unresectable  biliary or pancreatic cancer between November 2014 and May 2016 were prospectively enrolled in this study. The enteral nutrient Racol®, which includes omega-3 fatty acids, was administered at a dose of 2 to 4 packs (1 pack contains 200 kcal/300 g of omega-3 fatty acids) per day. Parameters were measured pre-administration, and at 4 and 8 weeks after the administration. Patients with pancreatic cancer underwent pancreatic function diagnostant (PFD) test. Then, these patients were given the pancreatic digestive enzyme supplement Lipacreon® (150 mg, 12C/day) for 4 weeks starting 4 weeks after initiating the enteral nutrient. This study was approved by the Institutional Review Board (IRB), and all patients provided written informed consent before participating in this trial.

Primary outcome measures: Body weight and skeletal muscle mass. Secondary outcome measures: Blood test data (EPA concentration, EPA/AA ratio, Glasgow prognostic score, RTP, neutrophil count, IL-6, natural killer cell activity, HbA1c, CEA, and CA19-9).

Results: Twenty-two patients were enrolled. No adverse effects were observed in the patients studied. In all 22 patients, there was a significant increase from pre-administration value  in skeletal muscle mass (p=0.004 and 0.001, respectively) at 4 weeks and 8 weeks and in body weight at 8 weeks (p=0.031).

For 14 patients with pancreatic cancer, significant increase in muscle mass was observed at 4 and 8 weeks (p=0.020 and 0.032, respectively). However, there was no significant difference between the muscle mass at 4 and 8 weeks. As for body weight and other parameters, there was no significant difference.

Conclusion: Nutritional support with omega-3 fatty acids for the patients receiving chemotherapy for unresectable biliary or pancreatic cancer increased skeletal muscle mass and improved cancer-related cachexia, while additional pancreatic digestive enzyme was not associated with increase in skeletal muscle mass or body weight.
 

68.06 Colorectal Cancer Outcome Disparities Increase with Distance from Treating Facility

Posted on January 26, 2017

S. P. Beierle1, J. McLoughlin1, R. Heidel1, L. Gregory1, M. Casillas1, A. J. Russ1  1University Of Tennessee Graduate School Of Medicine,Surgery,Knoxville, TN, USA

Introduction:  Outcomes for colon cancer have improved over the last thirty years due to improved emphasis on screening and better treatment options.  However, various regions of the United States remain below the expected outcomes for colon cancer.  We hypothesized that rural counties especially in the Appalachian region had worse outcomes for colon cancer and the reasons may be multi-factorial. 

Methods:  We queried the National Cancer Database (NCDB) for all patients diagnosed with an invasive colon cancer from 2008 – 2013.  A total of 712,172 patients were identified in the database.  We focused on the South Atlantic and West South Central States which included the states and counties within the defined Appalachian region. We analyzed clinical and pathologic features, socioeconomic factors, distance, and outcomes. Tests for normal distribution, Odds ratio, and Logistic regression were performed.

Results: Of the 712,172 patients identified, we focused on 186,700 patients in the South Atlantic and West South Central states with invasive colon cancer. After accounting for variations in insurance coverage, age, race, income, education, and comorbidities; living beyond 20 miles from the treating hospital increased the likelihood of presenting with metastatic disease (p<0.001).   Having no insurance was an independent predictor of presenting with metastatic disease (p<0.001). When evaluating for race , African Americans were 27% more likely to present with metastatic disease at diagnosis than whites [OR 1.27 (p= <.001, 95% CI = 1.234-1.309)]. Additionally the 30 day mortality was higher for African Americans than Caucasians (OR 1.288) and much higher for Charleson Deyo scores of 1 or 2 (OR 6.3 and 7.6). When comparing comorbidities using the Charleson Deyo score, having a known comorbidity corresponded with a decreased likelihood of presenting with metastatic disease at diagnosis (OR 0.837 for 1 comorbidity) and (OR 0.828 for 2 or more comorbidities) (P<.001 for both).

Conclusion: In summary, distance from the treating medical facility as an indicator of rurality confirmed rural communities remain a marker for worse colon cancer outcomes compared to urban communities.  Those with no insurance, distance > 20 miles from the treating hospital and African-American race correlated with worse outcomes. Our results suggest that rural communities are undergoing insufficient screening tests for colon cancer given the higher risk of presenting with metastatic disease.  Further, the risk of presenting with advanced disease decreased with increasing comorbidities further suggesting a lack of medical access for those in rural communities.  

 

68.05 Transplant Offers Survival Benefit Over Resection for Patients with HCC and Preserved Liver Function

Posted on January 26, 2017

J. B. Liu1,2, T. B. Baker4, N. Suss3, M. S. Talamonti2,3, K. K. Roggin2, D. J. Winchester2,3, M. S. Baker2,3  1American College Of Surgeons,Chicago, IL, USA 2University Of Chicago,Chicago, IL, USA 3Northshore University Health System,Evanston, IL, USA 4Northwestern University,Chicago, IL, USA

Introduction:
Prior studies from large national datasets comparing transplantation and resection for hepatocellular cancer (HCC) have not appropriately controlled for liver function. Previous multi-institutional series comparing transplantation and resection have included small numbers of patients with preserved liver function while also including those with decompensated cirrhosis. The benefit of transplantation relative to resection in patients with preserved liver function and potentially resectable HCC continues to be subject of considerable debate. 

Methods:
We evaluated patients from the National Cancer Data Base (NCDB) undergoing treatment for HCC between 2010 and 2013 with calculated MELD scores <11. Patients undergoing resection were 1:1 propensity-matched to patients undergoing liver transplantation based on age, gender, comorbidity burden, tumor size, tumor multiplicity, pathologic stage, margin status and MELD score. Logistic regression models with robust standard errors were constructed to examine 30- and 90-day mortality. Unadjusted and adjusted survival analyses were conducted using Kaplan-Meier and shared frailty models.

Results:
2,463 patients underwent operative management for HCC. Patients undergoing resection were more likely to have positive resection margins than those undergoing transplantation (7.0% vs. 0.3%, p <0.0001). After propensity matching, 854 patients were included in our study: 427 underwent resection and 427 underwent transplantation. Rates of 30- (1.9% vs 1.9%, p = 1.00) and 90-day mortality (3.3% vs 3.0%, p = 0.85) were identical between matched cohorts. Median follow-up was 551 days for those undergoing resection and 607 days for those undergoing transplantation. Patients undergoing resection demonstrated lower rates of overall survival relative to those undergoing transplantation in unadjusted analysis (median overall survival 39% vs not reached, p < 0.0001, log-rank test)  and an increased risk of death in shared frailty models (hazard ratio 2.21 [95% confidence interval 1.54-3.17]).

Conclusion:
Individualized care models are the cornerstone of treatment pathways for patients with HCC. In the subset of those with preserved liver function, there is active controversy as to whether resection or transplant offer superior overall survival rates for these patients. This propensity matched analysis of a large national database demonstrates a clear survival advantage for transplantation. Further prospective randomized clinical trials are needed to validate these findings.
 

68.04 A Fast and Frugal Decision Tree Model to Predict Opioid Adverse Events Following Oncologic Resection

Posted on January 26, 2017

S. A. Brownlee1, S. G. Pappas2, L. A. Gil1, A. Cobb1,2, P. C. Kuo1,2, A. N. Kothari1,2, G. J. Abood2  1Loyola University Medical Center,One:MAP Division Of Clinical Informatics And Analytics,Maywood, IL, USA 2Loyola University Medical Center,Department Of Surgery,Maywood, IL, USA

Introduction: Pain management is a crucial aspect of cancer care, particularly in patients undergoing surgical tumor resection. An increasing awareness of the potential hazards of opioid use, coupled with the high rate of opioid utilization by cancer patients, necessitates further study of risk factors for opioid-related adverse events in patients undergoing oncologic resection. The objective of this study was to construct a simple decision tree model to predict patients likely to experience an opioid-related adverse event following an oncologic resection.

Methods: The Healthcare Cost and Utilization Project (HCUP) State Inpatient Database (SID) and State Emergency Department Database (SEDD) from the state of California for the years 2006-2011 were linked to define the population of interest. Patients undergoing one of four elective oncologic resection procedures (esophagectomy, lung lobectomy, hepatic resection, and colectomy) were included for study. The primary endpoint was an opioid-related adverse event during the year following surgery. A fast and frugal decision tree was constructed to predict the factors that most contributed to the occurrence of an opioid-related adverse event.

Results:  148 699 patients undergoing one of four oncologic resection procedures in CA during 2006-2011 met inclusion criteria. Of these, 230 (0.2%) experienced an opioid-related adverse event in the year following the procedure. Recursive partitioning analysis of the cohort revealed age, income, length of stay after procedure, and comorbidity index as the most significant predictors of opioid-related adverse event, with age being the strongest predictor. For patients less than 63 years old, income level was the next strongest predictor of an opioid event.

Conclusions: Though rare, opioid-related poisonings and adverse events are serious complications for cancer patients undergoing surgical resection. Through the use of four readily-obtainable patient variables (age, income level, length of stay, and comorbid disease burden), this simple prediction model may provide clinicians with a practical tool to help decrease the frequency of opioid-related adverse events in a particularly vulnerable population.  

68.03 Impact of Endocrinologist and Surgeon Density on Thyroid Cancer Survival

Posted on January 26, 2017

A. D. McDow1, W. E. Zahnd1, P. Angelos2, N. Lanzotti1, J. D. Mellinger1, S. Ganai1  1Southern Illinois University School Of Medicine,General Surgery,Springfield, IL, USA 2University Of Chicago,Endocrine Surgery,Chicago, IL, USA

Introduction:  

Thyroid cancer is the most rapidly increasing malignancy in the United States. Prior analysis of rural-urban differences in population-level thyroid cancer incidence and survival revealed that lower incidence rates were seen in rural counties, which were also associated with significantly lower survival. In this study, we sought to evaluate the impact of provider density on outcome. We hypothesized that survival would be improved for patients living in counties with greater density of endocrinologists and/or thyroid surgeons.

Methods:  
An observational study was performed on 90,286 patients who underwent surgical management of follicular and papillary thyroid cancer using the Surveillance Epidemiology and End Results (SEER) database from 2000-2012. United States Department of Agriculture Rural Urban Continuum Codes were used to categorize counties as urban or rural. Density of general surgeons and otolaryngologists (i.e., the number of potential thyroid surgeons), as well as the density of endocrinologists per 100,000 residents were calculated per county. Multivariable Cox regression analysis was used to assess the relationship between provider density and cause-specific survival controlling for demographic, socioeconomic, and treatment characteristics.

Results: 

Patients were 78.5% female, 91.3% resided in urban counties, and 55.5% were over 45 years old. 70.6% presented with localized disease and 85.9% underwent total thyroidectomy. Median endocrinologist density was 1.4 per 100,000 and surgeon density was 14.8 per 100,000. 15.5% of patients lived in a county without an endocrinologist and only 1.7% lived in a county without a surgeon. Decreased survival was noted for those living in counties below the median density of surgeons (Log rank p=0.02) and endocrinologists (p=0.004). Cox regression analysis demonstrated endocrinologist density was significantly associated with improved survival (HR 0.89; 95% CI, 0.82-0.97; p=0.007), suggesting that an increase in one endocrinologist per 100,000 people improves survival odds by 11%. Living in a rural county (HR 1.29; 95% CI, 1.07-1.56; p=0.009), age greater than 45 years (HR 13.00; 95% CI, 10.20-16.58; P<0.001), male gender (p<0.001), and advanced stage (p<0.001) were also independently associated with lower survival. There was no significant association between surgeon density and survival (HR 0.99; 95% CI, 0.98-1.00; p=0.06). 

Conclusion: 

This study demonstrates that endocrinologist density is significantly associated with improved survival in patients with follicular and papillary thyroid cancer.  There was no association between surgeon density and survival, although this variable may not reflect the impact of surgeons with a focused interest in thyroid or endocrine surgery. The findings may reflect the importance of an endocrinologists’ role in diagnosis and treatment of thyroid cancer, or as a surrogate marker for counties with better overall access to care.

 

68.02 Indications for the Use of Total Parenteral Nutrition in Patients Undergoing Pancreaticoduodenectomy

Posted on January 26, 2017

C. E. Worsh1, T. Tatarian1, A. Singh1, M. J. Pucci1, J. M. Winter1, C. J. Yeo1, H. Lavu1  1Thomas Jefferson University,Department Of Surgery, Jefferson Pancreas, Biliary And Related Cancer Center,Philadelphia, PA, USA

Introduction:  Total parenteral nutrition (TPN) has historically been used conservatively in the management of patients undergoing pancreaticoduodenectomy (PD). In this study, we set out to identify the indications for and outcomes associated with TPN use in a high volume pancreatic surgery center.

 

Methods:  With IRB approval, we retrospectively queried our institution’s pancreatic surgery database and identified patients who received TPN after undergoing PD from 2006 through 2015.

 

Results: Of 1246 patients who underwent PD, 232 (19%) received TPN perioperatively. Sixty-seven percent were male and 50% had a soft pancreas. The most common postoperative complications requiring the initiation of TPN were delayed gastric emptying (DGE, n=131, 56%), pancreatic fistula (n=51, 22%), and generalized malnutrition (n=25, 11%). The median day of TPN initiation was POD 4 (range: minus 31 to 22), with a median usage of nine days (range: 1 to 115), at a cost of $650 to $950 per day. Forty-four (19%) patients were on TPN for a short period of time (three days or less), primarily those diagnosed with isolated DGE without associated complications (p=0.02). On upper GI examination, short-term TPN patients predominately had evidence of anastomotic edema (p=0.03), whereas patients on long-course TPN therapy (>3 days) tended to show evidence of gastric aperistalsis. Seventy-seven percent of TPN patients underwent postoperative CT imaging, of which half were found to have drainable intraabdominal fluid collections, predominately those on long-term TPN therapy (p=0.0012). Hyperglycemia (glucose >200 mg/dL, 34%) was the most common complication resulting from TPN use, while central line infections (3%) were rare. Readmissions (35%) were most commonly due to poor oral intake (27%). The 30-day mortality rate in the overall TPN cohort was 3.4% compared to our institutional no-TPN rate of 0.8%.

 

Conclusions: In modern PD surgery, TPN use is a critical and safe adjunct to aid in the rescue of patients from postoperative complications. However, an opportunity exists to limit TPN overuse by avoiding initiation in patients who have DGE secondary to anastomotic edema and focusing TPN use to patients who have additional PD associated complications such as pancreatic fistula or intraabdominal fluid collections.

 

 

67.10 Comparing Pathological T stage with Next Generation Sequencing in Melanoma

Posted on January 26, 2017

L. Selesner1, M. Renzetti1, I. Soliman1, H. Wu1, B. Luo1, A. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, F. Zih1, J. M. Farma1  1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA

Introduction:  Molecular profiling of primary cancers is becoming an important technique to evaluate and personalize treatment for patients with melanoma.  We have investigated mutations in 50 different targetable cancer-related genes using Next Generation Sequencing (NGS). This study uses molecular profiling data to examine the relationship between these mutations and the pathological primary thickness in a cohort of patients with malignant melanoma. 

Methods:  A retrospective study of a prospective dataset was performed that included patients with both primary and recurrent malignant melanomas (MM). From this cohort of patients, we analyzed tissue samples for somatic mutations in targeted regions of 50 cancer-related genes. Clinical and pathological data was collected. Statistical analysis was performed to identify mutations based on the pathological T stage of the primary tumor. The mean number of mutations per person presenting at each T stage was then investigated.

Results: We collected specimens from 135 patients with melanoma. The median age of diagnosis was 65 years (range 24-90) and 63.7% were male (n=86). At last follow up, 64 had no evidence of disease, 46 were alive with disease, 20 died of disease, 2 died of other causes, and 3 had an unknown status. Of the tissues tested, 4 presented as pathological T stage 1 (3.5%), 26 as T stage II (22.6%), 33 as T stage III (28.7%), and 50 as T stage IV (43.5%). At T stages I, II, III, IV averages of 1.75, 1.19, 1.78 and 1.62 mutations per person were attained (p= 0.44). Among the mutations found, NRAS and BRAF mutations were frequently expressed in each of the T stages. Of the patients presenting as T stage I, 50% had a NRAS mutation (n=2). At T stage II, 30.8% of the patients had a NRAS mutation (n=8). At T stage II, 42.8% had a NRAS mutation (n=14) and at T stage IV, 26% of the patients had the mutation (n=13) (p=0.52). In reference to BRAF, 25% of the T stage I patients (n=1), 34.6% of the T stage II patients (n=9), 24.2% of the T stage III patients (n=8), and 22% of the T stage IV patients (n=11) had a mutation in at least one of the BRAF genes (p=0.71). Also of interest, TP53 was the most common mutation in the patients presenting at T stage IV with 28% of this cohort expressing this mutation (Figure 1).

Conclusion: Using our NGS platform in patients, we identified the most prevalent mutations in our cohort of patients that presented at the four different pathological T stages (I-IV). We found that for T stage I, the most frequent mutation was in NRAS. For T stages II and III, mutations in NRAS and at least one of the BRAF genes, were expressed in the highest number. Finally, TP53 and NRAS mutations were most common in the T stage IV patients. While there was no statistical significance found comparing the pathological T stage and genetic mutations, the data warrants further investigation with a larger sample size.

 

67.09 Clinical and Epidemiological Factors Associated with Suicide in Colorectal Cancer

Posted on January 26, 2017

T. Pham1, A. Talukder1, N. Walsh1, A. Lawson1, A. Jones1, E. J. Kruse1  1Medical College Of Georgia,Surgery,Augusta, GA, USA

Introduction:  Increased suicidal tendencies among cancer patients have been well documented. To date, there has been no specific examination of suicide rates and factors associated with suicide in colorectal cancer. The aim of this study is to examine suicide incidence and associated factors in colorectal cancer patients from 1973 to 2013.

Methods:  The Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute was queried to identify patients with colorectal cancer. The study included mortality and demographic data from 1973 to 2013. Comparison data with the general United States population was derived from the Centers for Disease Control and Prevention’s National Center for Injury Prevention and Control using the Web-based Injury Statistics Query and Reporting System (WISQARS). Standardized mortality ratios (SMRs) and their 95% confidence intervals (95% CIs) were calculated, and multivariable logistic regression models generated odds ratios (ORs) for the identification of factors associated with suicide in colorectal malignancy.

Results: Overall, 1347 suicides among 884,529 patients were identified. Of the patients committing suicide, almost half, 1158 (84%), were over 80 years old. There was no statistically significant difference in suicide rate with respect to age, marital status, median household income, surgical intervention, or histologic subtype. Whites were significantly more likely to commit suicide than non-whites ( OR 2.28, 95% CI 1.89-2.75 P< 0.001), and males were significantly more likely than females (OR 5.635, 95% CI 4.85-6.54, P <0.001). Most suicides occurred in patients with distal lesions in either the sigmoid or rectosigmoid junction (P<0.001). Stage at diagnosis did not have a statistically significant relationship to suicide. SMRs for patients with colorectal cancer were 4.24 for females (95% CI, 3.69- 4.86), 1.35 for males (95% CI, 1.28- 1.43), 0.38 for African-Americans (95% CI, 0.28- 0.52), 1.77 for Whites (95% CI, 1.68- 1.87), and 0.90 for other races (95% CI, 0.72- 1.12). 

Conclusion: Identification of evidence-based risk factors associated with suicide among patients with colorectal cancer is an important step in the development of screening strategies and management of psychosocial stressors. Race and gender appear to influence suicide rates in patients with colorectal cancer. Females with colorectal cancer demonstrated approximately four times the suicide rate of the gender-matched population. These results, coupled with further studies and analyses, could be used to formulate a comprehensive suicide risk factor scoring system for screening all cancer patients. 

 

67.08 Transthoracic Versus Transhiatal Esophagectomy: Is there a More Favorable Approach?

Posted on January 26, 2017

M. Berrata3, R. Shridhar2, P. Briceno1, S. Kucera4, A. Patel5, J. Lee1, J. Huston1, K. Meredith1  1Florida State University College Of Medicine/Sarasota Memorial Health Care System,Gastrointestinal Oncology,Sarasota, FL, USA 2University Of Central Florida,Radiation Oncology,Sarasota, FL, USA 3Florida State University College Of Medicine,Sarasota, FL, USA 4Florida State University College Of Medicine/Sarasota Memorial Health Care System,Endoscopic Oncology,Sarasota, FL, USA 5Florida Cancer Specialists,Medical Oncology,Sarasota, FL, USA

Introduction:  Esophageal cancer continues to increase in incidence worldwide. The long-term survival for patients with locally advanced esophageal cancer remains poor despite improvements in multi-modality care over the last several decades. Surgical resection remains piviotal in the management of patients with esophageal cancer.  The myriad of techniques preclude the recommendation of a standard approach to esophageal resection. We investigate the difference in outcomes between the trans-thoracic (TT) and trans-hiatal (TH) approach in esophageal cancer patients undergoing esophagectomy. 

Methods: A prospectively managed esophagectomy database was queried for patients undergoing trans-thoracic or trans-hiatal esophagectomy between 1996 and 2015. Basic demographics, tumor characteristics, operative details, and post-operative outcomes were recorded. Continuous variables were compared using the Kruskal Wallis or the ANOVA tests as appropriate. Pearson’s Chi-square test was used to compare categorical variables. All statistical tests were two-sided and an α (type I) error <0.05 was considered statistically significant. 

Results: We identified 846 patients who underwent esophageactomy with a mean age of 64 ± 10 years, 714 (84.4%) TT and 132 (15.6%) TH. There were 239 (33.5%) patients within TT that underwent minimally invasive approach (MIE) and 63 (47.7%) within TH that underwent MIE.  Post-operative complications occurred in 207 (29.0%) patients in the TT and 59 (44.7%) in the patients who underwent TH p<0.001.  The most common complications in TT vs TH were anastomotic leak: 4.3% vs 9.8% p=0.01; anastomotic stricture 7% vs 26.5%, p<0.001; pneumonia 12.6% vs 22.7% p<0.002; aspiration 1.7% vs 15.9%, p<0.001; wound infection 4.5% vs 10.6% p=0.004; atrial fibrillation 13.6% vs 14.4%, p=0.8; and pleural effusion 3.2% vs 11.4%, p<0.001.  There were 13 (1.5%) mortalities, 11 (1.5%) in the TT and 2 (1.5%) in the TH cohort, p=1. Neoadjuvant therapy was administered in 459 (64.3%) TT and 78 (59.1%) TH patients, p=0.2. R0 resections were comparable amongst groups 679 (95.6%) in TT and 122 (93.1%) in TH p=0.2. However the lymph node harvest was higher in the TT patients 12±8 compared to 9±6 in the TH group, p<0.001 and 18±9 in the MIE TT vs 9±6 in the MIE TH, p=0.001. 

Conclusion: While both TT and TH are acceptable techniques for esophageal resection, the trans-thoracic approach is associated with fewer post-operative complications.  Pulmonary complications which are traditionally believed to be lower in the TH groups were also higher in patients undergoing the trans-hiatal approach. Additionally, patients undergoing TT demonstrated superior nodal harvest which may have implications in oncologic outcomes.
 

67.07 Plantar Foot Melanoma – The Inaccuracy of the Initial Biopsy and Inadequacy of Resection Margins

Posted on January 26, 2017

J. E. Miller1, S. A. Debolle1, T. N. Ballard2, A. B. Durham3, J. H. Kozlow2  1University Of Michigan,Medical School,Ann Arbor, MI, USA 2University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA 3University Of Michigan,Department Of Dermatology,Ann Arbor, MI, USA

Introduction:  The plantar surface of the foot is unique due to its ridged epidermis and ability to undergo hyperkeratosis. It is unclear if melanomas arising on the plantar surface of the foot behave clinically similar to melanomas in other areas of non-glabrous skin, making clinical decision-making and treatment more challenging. The two specific aims of this study were to determine the accuracy of the Breslow depth of the initial biopsy and to determine the incidence of positive microscopic margins following an intended curative excision.

Methods:  In this retrospective study, we reviewed the charts of 103 patients with plantar foot melanoma treated at the University of Michigan from 1997 to 2015. The Breslow depth from the initial biopsy pathology report was compared to the Breslow depth in the final pathology report following either repeat biopsy or definitive surgical excision. These results were compared both in absolute Breslow depth and for changes in Tumor staging. We evaluated the microscopic margin status on the pathology report and used published guidelines to determine if appropriate surgical margins were taken in the intended curative resection.

Results: A total of 46 patients (45.5%) had an increase in Breslow depth compared to their initial biopsy, with 34 (33.7%) having an increase substantial enough to change their tumor staging. A total of 16 patients (15.5%) had positive microscopic margins following an intended curative excision. Patients with stage T3 and T4 tumors had the highest incidence of positive microscopic margins, with 21.4% and 30.0%, respectively, requiring a re-excision. Of the 70 patients treated with surgical margins in accordance with NCCN guidelines, 12 (17.1%) had positive microscopic margins, whereas only 1 (6.3%) of the 16 patients treated with margins larger than guideline recommendations had positive microscopic margins.

Conclusion: The surgical management of plantar foot melanoma depends on the Breslow depth of the tumor. Current practices often use the initial biopsy pathology report to determine Breslow depth of the tumor, however our findings show that these values are often incorrect and frequently under-stage the actual tumor depth. Additionally, clinicians should be aware of the high rate of positive microscopic margins in this area of the body, even when standard guidelines are followed. This information will allow for improved informed shared decision making with patients and will affect the timing of reconstructive procedures.

67.06 Current surgical practice in prevention of lymphedema in breast cancer patients

Posted on January 26, 2017

D. Balaji1, T. Hughes2, A. Chagpar1  1Yale University,Surgery,New Haven, CT, USA 2McPherson Hospital,Surgery,McPherson, KS, USA

Introduction:   Recently, more data has emerged noting that avoidance of IVs, blood pressures and blood draws do not significantly increase lymphedema after breast cancer surgery, while resistance exercise is effective in reducing lymphedema.  We sought to determine surgeons’ practices in preventing lymphedema after breast cancer surgery and factors associated with variation in this.

Methods:   An anonymous survey was posted on the American College of Surgeons’ Communities online platform.  From June 28, 2015 to August 9, 2015, 273 surgeons responded to the survey.  In addition to their demographics and practice patterns, surgeons were asked about their perceptions regarding the prevalence of lymphedema after sentinel lymph node biopsy (SLNB) and axillary node dissection (ALND).  Bivariate analyses using non-parametric statistics were performed using SPSS Ver. 21 software.

Results:  56.4% of respondents were 40-60 years of age; 52.3% had been in practice 11-30 years.  29.7% had solely breast practices; 14.7% were academic, 44.3% in private practice.  85% of respondents felt the risk of lymphedema after SLNB was < 5%; 52.1% felt that the risk of lymphedema after ALND was <10%.  In terms of their routine practice, 49.1% said they advise avoiding ipsilateral blood pressures, 58.6% avoid ipsilateral blood draws/ivs.  Only 3.7% routinely recommended a sleeve to avoid lymphedema, while 21.6% recommended a sleeve for air travel.  31.5% encouraged lifting weights, while 2.2% advised patients to avoid doing so.  Surgeons who were in solely breast-related practices were more likely to routinely encourage lifting weights (53.1% vs. 22.5%, p<0.001) and advocate sleeves for air travel (44.4% vs. 12.0%, p<0.001).  They were also more likely to quote a rate of >20% of lymphedema after ALND (20.5% vs. 7.2%, p<0.001).  There was no significant variation in recommendations regarding avoidance of ivs, blood pressures, or routine sleeve use based on surgeon demographic or practice type or location.

Conclusion:  Despite mounting data that lymphedema can be reduced with weight-bearing exercise, only a third of surgeons routinely recommend this.  There seems to be variation in recommendations to avoid blood pressures and ivs among surgeons, with roughly half routinely recommending to avoid these after lymphadenectomy, but this variation is not mediated by surgeon demographic or practice type.  Consensus guidelines may therefore be indicated regarding appropriate prevention of lymphedema in breast cancer patients.

 

67.05 The Effect of Adjuvant Chemotherapy on Overall Survival in Patients with Synovial Sarcoma

Posted on January 26, 2017

C. C. Vining1, A. J. Sinnamon1, M. G. Neuwirth1, B. L. Ecker1, R. R. Kelz1, D. L. Fraker1, R. E. Roses1, G. C. Karakousis1  1Hospital Of The University Of Pennsylvania,Department Of Endocrine And Oncologic Surgery,Philadelphia, PA, USA

Introduction:
The management of stage I-III synovial sarcoma is primarily surgical with consideration of adjuvant radiation. However, the role of adjuvant chemotherapy (AC) remains less well-defined limited to small institutional series. Using a large national dataset we sought to identify factors associated with receipt of AC and to evaluate impact on overall survival (OS).

Methods:
Patients with stage I-III synovial sarcoma 2004-2012 undergoing resection were identified in the National Cancer Data Base. Patients were excluded if they received any neoadjuvant therapy or had incomplete grade, size, or adjuvant therapy data. Chi-square and multivariable logistic regression was used to identify factors associated with receipt of AC (univariate p-value<0.05 for inclusion in multivariable model). Clinicopathologic factors and adjuvant therapies associated with improved OS were identified with univariate and multivariable Cox proportional hazard modeling and the Kaplan-Meier method, applied to the overall cohort and to subgroups stratified by stage.

Results:
From 2004-2012, 597 patients underwent resection with evaluable data. Median age was 41 (IQR 29-54) and 302 were female. Four-hundred sixteen tumors were high grade, 204 were 5-10cm, and 97 were >10cm. One hundred eighty-four patients received AC, 311 received adjuvant radiation, and 102 received both. Factors associated with receipt of AC in multivariable analysis included age <40y (OR 2.49), high grade pathology (OR 2.04), size (5-10cm OR 2.45; >10cm OR 3.52), and positive margins NOS (OR 5.67). In multivariable analysis, factors significantly associated with worse OS included age>40y (HR 2.57), Charlson-Deyo comorbidity score ≥ 2 (HR 3.18), monophasic histology (HR 2.89), size 5-10cm (HR 2.06), >10cm (HR 2.12), high grade (HR 3.24), positive lymph nodes (HR 15.9), omission of adjuvant radiation (HR 1.64), and macroscopic surgical margins (n=5, HR 8.53); notably, AC was not significantly associated with improved OS. However, when patients were stratified by stage, AC was associated with improved OS among stage III patients but not in lower stage groups. This association remained significant in multivariable analysis (HR 0.59, p=0.037). The stage III group (n=227) was comprised almost entirely of high grade tumors >5cm, as confirmed LN metastasis were rare (n=3). Ninety-eight (43%) of these patients received AC, compared to 24% of stage II (82/339), and 13% (4/31) of stage I.

Conclusion:
In this large national dataset AC in resected synovial sarcoma was associated with improved OS in patients with stage III disease but not in lower stages. Less restricted use of this therapy may be warranted considering it was administered to less than half of these patients.
 

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