06.20 Sarcopenic obesity predicts poor outcome after hepatectomy for colorectal liver metastases

B. J. Kim1, J. W. Denbo1, J. Ma2, G. Passot1, M. H. Katz1, Y. S. Chun1, C. Conrad1, J. Vauthey1, T. A. Aloia1  1University Of Texas MD Anderson Cancer Center,Surgical Oncology,Houston, TX, USA 2University Of Texas MD Anderson Cancer Center,Department Of Radiology,Houston, TX, USA

Introduction:
Although recent studies suggest that sarcopenia (ratio of skeletal muscle volume to height) correlates with complications after hepatectomy, these studies are confounded by variability in tumor and procedure factors.  This study focused on a large cohort of colorectal liver metastasis (CLM) patients surgically treated exclusively with open formal right hepatectomy to isolate the influence of nutritional and physical fitness factors on post-hepatectomy outcomes. 

Methods:
A prospectively maintained institutional liver surgery database was queried to identify a continuous set of CLM patients treated with right hepatectomy as their first liver directed therapy.  Preoperative CT imaging was used to acquire skeletal muscle area, visceral adipose area and subcutaneous adipose area using published techniques and advanced imaging software.  These measures were standardized to height (m2) to define the skeletal muscle index, visceral adipose index, subcutaneous adipose index, sarcopenia and sarcopenic obesity.  These indices were compared along with patient factors including preoperative chemotherapy, postoperative morbidity and mortality. 

Results:
180 patients met the inclusion criteria including 108 men and 72 women with a median age of 57 years.  72.1% received pre-hepatectomy chemotherapy.  The prevalence of sarcopenia and sarcopenic obesity was 35% and 17%, respectively.  Cohort outcomes included severe complication rate (30%), liver failure rate (6.7%), readmission rate (6.1%), 30-day mortality rate (2.8%) and 90-day mortality rate (4.4%).  Sarcopenia was associated with higher 30-day mortality (6.3% vs 0.9%, p=0.05), and sarcopenic obesity was further associated with pneumonia (9.7% vs 2.0%, p=0.07), bile leak (16.1% vs 6.0%, p=0.05) and liver failure (16.1% vs 4.7%, p=0.02).  In patients over 65 years old, sarcopenic obesity was also associated with a higher 1-year all-cause mortality rate (21.4% vs 2.6%, p=0.05).

Conclusion:
After controlling for tumor factors and case magnitude by limiting the patient cohort to only right hepatectomies, sarcopenic obesity was found to significantly impact post-hepatectomy outcomes, including longer-term survivals in elderly patients.  Given that most patients have ample time for intervention during preoperative systemic therapy administration, sarcopenia should be assessed at diagnosis of liver metastases and remedied with nutritional and physical prehabilitation prior to surgery.
 

06.19 Rates and Trends in Utilization of Palliative Therapies for Stage IV Rectal Adenocarcinoma

A. S. Kulaylat1, C. S. Hollenbeak1, D. B. Stewart1  1Penn State Hershey Medical Center,Surgery,Hershey, PA, USA

Introduction: Despite data suggesting decreased cost of care and improved quality of life for patients with terminal cancers, palliative therapy is a frequently under-utilized resource in a variety of malignancies. There is little data on patterns of implementation of palliative therapy in the management of stage IV rectal cancer in the United States.

Methods: Patients diagnosed with rectal adenocarcinoma between 2004 and 2011 were identified within the National Cancer Database (NCDB); those with stage IV disease who did not undergo definitive surgery due to patient or disease-related contraindications comprised the study cohort. Patients undergoing palliative interventions were indicated by a specified variable within the NCDB and were stratified by type of palliation (surgery, radiation, systemic, pain control, a combination thereof, or referral without specified intervention). Multivariable logistic regression was used to identify patient factors associated with receipt of palliative therapy.

Results:A total of 11,245 patients were included in this study, of which 2,314 (20.6%) received palliative therapy. While the rates of patients receiving referrals for palliative therapy (Fig. 1) without a specified intervention did increase significantly (0.1% to 1.5%, p=0.001), the overall utilization of palliative interventions did not change significantly over time (19.4% to 23.0%, p=0.14). During the study period, the use of chemotherapy nearly doubled from 4.7% to 8.7% (p<0.001), while the use of palliative radiation diminished significantly from 7.6% to 5.6% (p=0.001). Patient characteristics associated with the utilization of palliative interventions included patient age greater than 60 years (odds ratios [OR] ranging from 1.17 to 1.35 for age groups over 60, all p<0.02) and increasing chronic comorbidities (OR 1.20, p=0.004 for one comorbidity; OR 1.24, p=0.036 for two or more comorbidities). Differences in gender and race, however, were not associated with receipt of palliative therapy. Patients in the highest income quartile were less likely to undergo palliative interventions (OR 0.84, p=0.018), but insurance status did not have a significant effect on utilization of palliative methods.

Conclusion:For patients with stage IV rectal adenocarcinoma who were managed without curative intent, rates of utilization of palliative therapy were consistently low, with patients who were older and more sickly being more likely to receive palliative care. While insurance and lower socioeconomic status did not appear to limit utilization, identification of barriers to receipt of palliative care requires further study.

 

06.18 Evaluation of Molecular Profile in High Risk Class 2 MelanomaDx Melanoma Patients

M. Renzetti1, I. Soliman1, H. Wu1, B. Luo1, H. Liu1, A. Olszanski1, S. Movva1, M. Lango1, S. Reddy1, F. Zih1, J. M. 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 providing valuable prognostic information on primary cancers with the potential to uncover actionable mutations. Our institution has been using NGS to examine mutations in 50 cancer-related genes. Here we examine molecular profiling of melanoma patients who were classified as Class 2 based on the MelanomaDx test.

Methods:  Melanoma patients who underwent both NGS and Melanoma Dx GEP testing, and were Class 2 were evaluated. Using NGS, we analyzed malignant melanoma (MM) tissue samples for somatic mutations in targeted regions of 50 common cancer related genes. We generally order this testing on advanced melanoma patients. Tissue samples were also sent for the Melanoma Dx test. Clinical and pathologic data were collected.

Results: We performed NGS on 133 patients with MM, and 18 of those patients also underwent MelanomaDx GEP testing and 15 were Class 2. In Class 2 patients, median age at diagnosis was 66 years (range 27-79) and 80% were male (n=12). Median follow up was 2 months (range 1-27). Location of the primary included upper extremity (n=4), trunk (n=4), and lower extremity (n=7). At presentation, 2 MM were stage I, 13 were stage II. All Class 2 tissue samples were taken from primary tumors. In total, 22 mutations were identified, affecting 12 unique genes. No mutations were found in 13.3% of patients (n=2), 33.3% had one mutation (n=5), 46.7% had 2 mutations (n=7), and 6.7% had 3 mutations (n=1). The most frequently identified mutations were BRAF (n=4), CDKN2A (n=3), NRAS (n=4), and TP53 (n=3) (Fig. 1).

40% of the patients had a MM recurrence (n=6), 83.3% of which had distant metastasis (n=5). Median time to recurrence was 16 months (range 9-53). Recurrent melanomas had 10 mutations over 7 unique genes. 4 patients had 2 gene mutations, and 2 only had 1. Most common gene mutations were BRAF (n=2) and NRAS (n=3).

Conclusion: Using both our NGS platform and MelanomaDx GEP for Class 2 MM patients, we identified that the most common mutations in both recurrent and nonrecurrent MM are BRAF and NRAS in 22.2% of patients each. Future studies will identify and correlate specific molecular profile patterns with treatment response and survival outcomes.

06.17 Utilization of External Beam Radiation in Differentiated Thyroid Cancer

C. M. Kiernan1, A. A. Parikh1, C. C. Solorzano1  1Vanderbilt University Medical Center,Nashville, TN, USA

Introduction: External beam radiation (EBRT) for differentiated thyroid cancer (DTC) is recommended in patients >45 years old, with locally advanced unresectable or metastatic disease. This study describes the patterns of EBRT utilization and overall survival of patients with DTC who received EBRT.

Methods:
A total of 46,095 patients diagnosed with DTC between 2003-2006 were identified using the National Cancer Database.  Patients with anaplastic thyroid cancer and patients with more than one cancer diagnosis were excluded. The use of EBRT was documented. Descriptive statistics, Kaplan Meier estimator of overall survival and multivariate cox-proportional hazards regressions were used.

Results:
A total of 546 (1.2%) patients received EBRT.  Patients in the EBRT cohort were on average older (60 vs. 48 years, p<0.001) and presented with larger tumors (4.2 vs. 3.5cm).  They were also more likely to have extrathyroidal extension (46% vs. 11%, p<0.001), positive lymph nodes (65% vs. 34%, p<0.001), positive margins (41% vs. 9%, p<0.001), and distant metastases (34% vs. 1%, p<0.001). The majority of patients in the EBRT group (60%) had stage IV disease at presentation. The 5-year overall survival (OS) was lower in the EBRT group (53% vs. 95%, p<0.001).  On subgroup analysis of patients >45 years of age who underwent total thyroidectomy and had gross extrathyroidal extension EBRT was also associated with decreased OS (84% vs. 42%, p<0.001).  Stage for stage, the 5-year OS was lower in the EBRT group: stage II (96% vs. 81%, p=0.001), stage III (92% vs. 75%, p<0.001) and stage IV (72% vs. 33%, p<0.001).  By cox-proportional hazards regression controlling for multiple patient and tumor factors, EBRT was associated with increased all-cause mortality (HR 2.76, CI 2.01-3.79, p<0.001).

Conclusion:
EBRT is used infrequently in DTC. Patients who receive EBRT are older with more advanced disease. In this large population database study, the utilization of EBRT was associated with decreased overall survival by multivariable analysis. Further study regarding the impact of EBRT on the quality of life of patients with DTC is needed.
 

06.16 Survival of Rectal Carcinoids by Extent of Surgery: A National Analysis of 1,900 Patients

B. Ezekian1, M. A. Adam1, B. F. Gilmore1, Z. Sun1, M. L. Cox1, M. C. Turner1, C. R. Mantyh1, J. Migaly1  1Duke University Medical Center,Department Of Surgery,Durham, NC, USA

Introduction:
Current National Comprehensive Cancer Network (NCCN) guidelines recommend local resection for rectal carcinoids ≤2 cm and radical resection for tumors >2 cm. However, given the limited data examining the appropriate extent of surgery for these lesions, we queried a national database to determine the impact of extent of resection on pathologic lymph node positivity and survival.

Methods:
Patients undergoing surgical treatment for non-metastatic, clinically-node negative rectal carcinoid were identified from the National Cancer Data Base (1998-2012). The association between extent of surgery, tumor size, and the likelihood of lymph node positivity was examined. Kaplan-Meier analysis was used to compare overall survival between patients undergoing local vs. radical resection.

Results:
In total, 1,900 patients were identified, of whom 1,644 (86.5%) were treated with a local resection and 256 (13.5%) were treated with a radical resection. Patient age, race, co-morbidities, and 30-day mortality were not different between groups (all p > 0.05). A vast majority of patients with tumors ≤2 cm received a local excision (88.96%), whereas most patients with tumors 2.1-4 cm (55.17%) or >4 cm (54.17%) received radical surgery. In patients who underwent radical resection, those with larger tumor size were more likely to have lymph node metastases (7.0% of patients with ≤2 cm tumors, 31.3% with 2.1-4 cm tumors, and 50.0% with >4 cm tumors). 5-year survival was not different in patients receiving local vs. radical surgery for tumors <4 cm (93% vs 93%, p = 0.67 for tumors ≤2 cm and 76% vs. 76%, p = 0.77 for tumors 2.1-4 cm).

Conclusion:
In this large cohort of patients with rectal carcinoids, we show that while survival appears to be equivalent between local vs. radical resection for rectal carcinoids up to 4 cm, the likelihood of lymph node metastases significantly increases with tumor size >2 cm. Thereby, current guidelines recommending radical resection for tumors >2 cm seem appropriate.
 

06.15 Renal Oncocytic Neoplasms; Observe, Excise or Ablate?

J. R. Van Roo1, B. L. Miller1, T. J. Ziemlewicz2, S. L. Best1, S. A. Wells2, M. G. Lubner2, J. Hinshaw2, F. Shi1, F. T. Lee, Jr.2, S. Y. Nakada1, E. Abel1  1University Of Wisconsin,Department Of Urology,Madison, WI, USA 2University Of Wisconsin,Department Of Radiology,Madison, WI, USA

Introduction:

Approximately 15-20% of renal masses are classified as oncocytomas, oncocytic neoplasms or chromophobe renal cell carcinomas (chRCC). Historically, oncocytic renal neoplasms were excised because of the risk for RCC and because definitive diagnosis of benign tumors was difficult. However, thermal ablation and surveillance have emerged as alternative treatment options for renal masses over the last decade. The purpose of this study is to evaluate outcomes for surgery, ablation, and active surveillance of oncocytic neoplasms.

Methods:

Patients with pathologic diagnosis of renal oncocytic neoplasms from 2003-2016 were identified. Clinical, radiologic and pathologic data were collected for each patient.  Oncologic outcomes, adverse events classified using Clavien system within 90 days of treatment, and renal functional outcomes were compared among patients treated surgically, using thermal ablation or with surveillance.

Results:

A total of 165 patients were identified with oncocytic renal masses including: 117 oncocytoma, 2 oncocytic neoplasms and 46 chRCC. Median tumor diameter was 2.9 cm [IQR 2-3.2] and median age was 67.3 years.  A total of 131 (79.4%) patients were asymptomatic at presentation. Charlson Comorbidity Index(CCI) was 0 in 65(39.4%) and ≥1 in 98(59.6%). Patients treated surgically were more likely to have larger tumor diameter compared to other modalities (p=<.0001). Patients treated surgically or with ablation were older and had higher CCI when compared with patients undergoing active surveillance. (p<0.01, 0.02)

Definitive management included surgery for 77(46.7%), thermal ablation in 32(19.4%), and active surveillance in 56(33.9%).  Median follow-up interval from diagnosis is 41 months [IQR 14-74]. Outcomes are displayed in table.  A total of 3(1.8%) patients developed metastatic RCC (mRCC), and 2(1.2%) patients have died of disease. In patients who developed mRCC, tumor size at presentation was 5,10, 13 cm and all patients were symptomatic at presentation.

Patients treated surgically had higher rates of complications and longer length of hospitalization (p<0.01, <0.01). Patients treated with radical nephrectomy were more likely to have decreased renal function and 13(7.9%) patients died from other causes during surveillance. 

Conclusion:

Renal oncocytic neoplasms have low metastatic potential overall.  Active surveillance and thermal ablation should be considered for patients with oncocytic tumors <4cm.

06.13 Surveillance strategies in the follow-up of melanoma patients: too much or not enough?

J. Kurtz2, G. Beasley1, K. Kendra1, T. Olencki1, A. Terando1, J. Howard1, D. Agnese1  1Ohio State University,Surgical Oncology,Columbus, OH, USA 2Doctor’s Hospital,General Surgery,Columbus, OH, USA

Introduction: After appropriate initial therapy for patients with stage II-III melanoma, there is no consensus regarding surveillance, thus follow up is highly variable among institutions and individual providers.  The NCCN recommends routine clinical exam and consideration of imaging for stage IIB-IIIC every 3-12 months with no distinction between stages.  Detection of recurrence is important as novel systemic therapies and surgical resection of recurrence can provide survival benefits.

Methods:   We retrospectively reviewed 369 patients with Stage II and III melanoma treated at Ohio State University from 2009-2015 who underwent surgery as primary initial therapy.  246 patients who were followed for a minimum of 6 months after completion of surgical therapy to achieve no evidence of disease status (NED) were included in this analysis while 123 were lost to follow up after surgery and were excluded.

Results: The rate of recurrence for stage IIA/IIB patients was 11% (14/123).  Eight of the 14 (57%) recurrences were detected by clinical symptoms or physical exam. Thirty-eight percent (47/123) of stage IIA or IIB patients were followed by clinical exam only while 64% (76/123) were followed with at least 2 serial chest x-rays. The median time to first chest x-ray after NED status was 4.7 months (n=76), median time to second chest-xray after NED status was 12.7 months (n=76), and 66% (50/76) continued to have additional serial chest x-rays.   At median follow-up of 35 months for the 123 patients with stage IIA/IIB, there was no difference in survival between those followed clinically (95% (95% CI: 0.88-.99)) versus those followed with at least 2 serial x-rays (96% (95% CI: 0.89-0.98).   For stage IIC/IIIA-C patients, recurrence was detected in 24% (29/123) at median follow-up 31.2 months.  Imaging detected 51% (15/29) of those recurrences in asymptomatic patients while 40% (14/29) had recurrence detected on imaging with associated clinical findings.  Eighty six percent (106/123) of stage IIC/IIIA-C patients were followed with at least 2 serial whole body PET/CT scans or whole body CT scans plus brain MRI; median time between NED status and second scan was 10.3 months.  Of stage IIC/stage III patients with recurrence, 68% (19/28) went on to surgical resection of the recurrence while 18 (64%) patients received B-RAF inhibitor therapy, immune blockade therapy, or combination therapy.

Conclusion: For stage IIA and IIB melanoma, surveillance chest x-rays did not improve survival compared to physical exam alone.  However for IIC and IIIA-C melanoma, where the recurrence rates are higher, routine whole body imaging detected recurrences not found on clinical exam leading to additional surgery and/or treatment with novel systemic therapies for the majority of patients. Detection of melanoma recurrence is important and specific sub stage should be used to stratify risk and define appropriate follow up.
 

06.12 Use Of Suprahepatic Occlusion Of The IVCFor Resection Of HCC With Tumor Thrombus In The Hepatic Vein

A. Li1, M. Wu1  1Eastern Hepatobiliary Surgery Hospital,SMMU,Shanghai, SHANGHAI, China

Introduction: To investigate the differences in the surgical approaches for resection of hepatocellular carcinoma (HCC) with tumor thrombus was extending into the hepatic vein using occlusion of the suprahepatic inferior vena cava (IVC) with occlusion forceps.

Methods: Between January 2011 and December 2013, 21 patients diagnosed with advanced HCC with tumor thrombi in the hepatic vein underwent hepatectomy and thrombectomy. Peri- and postoperative morbidity and mortality rates were evaluated prospectively and analyzed.

Results:Mean age of the patients was 47 years. Median primary tumor size was 12.0±4.0cm. All HVTT were removed using occlusion of the suprahepatic IVC with Satinsky vascular clamp. Pringle’s maneuver time was 19 minutes (range 15 to 24 minutes). Mean time of occlusion of the suprahepatic IVC was 10 minutes (range 8 to 20 minutes). Mean intraoperative blood loss was 600 mL (range 300 to 2,000 mL). Postoperative complications were seen in 10% of patients (n=2), included pleural effusion (n=2). Median follow-up was 38 months (range 2 to 72 months). The 1- and 2-year overall survival (OS) rates were 57% and 4%, respectively, while the 1- and 2-year recurrence rates were 94% and 96%.

Conclusion: This study showed that using occlusion of the suprahepatic IVC, resection for HCC with tumor thrombi in the hepatic vein can be performed safely and thereby avoid embolus rupture of tumor thrombus and air embolism, and may improve the prognosis of these patients. This method is especially suitable for unexpected, intraoperatively detected hepatic vein tumor thrombus.
 

06.11 Impact of High-Risk Microscopic Features Among Patients with Resected Stage II Colon Cancer

A. Ejaz2, L. Casadaban1, M. Kobialka1, A. V. Maker1  1University Of Illinois At Chicago,Chicago, IL, USA 2Johns Hopkins University School Of Medicine,Baltimore, MD, USA

Introduction:  The impact of negative prognostic factors among patients with stage II colon cancer is ill-defined. We sought to define the incidence and impact of microsatellite instability (MSI), lymphovascular invasion (LVI), and perineural invasion (PNI), features often not captured in large cancer population databases, on overall (OS), and recurrence-free survival (RFS) following resection among patients with stage II colon cancer.

Methods:  Using a prospectively-collected multi-institutional database across 8 hospitals, we identified 345 stage II colon cancer patients who underwent curative resection between 2010-2013. The impact of high-risk microscopic features (MSI, LVI, PNI) and clinicopathologic and treatment factors were evaluated using multivariate regression models. 

Results: In a subset of 175 patients for whom high-risk microscopic features were available, median patient age was 72 (IQR: 64, 81) years.  The majority of patients were white (77.7%) and female (52.6%).  On pathology, most patients had a T3 tumor (81.3%) with a mean of 20.9±10 lymph nodes examined.  High-risk microscopic features were common as 76.0% of patients had evidence of MSI-stable (63.2%), LVI (31.9%), or PNI (7.1%).  Adjuvant chemotherapy was administered in 30 (17.1%) patients. After a median follow-up of 37 months, 31 patients (17.7%) died within the study period and median overall survival (OS) was not reached. After adjusting for patient-, treatment-, and tumor-related factors, MSI-stable (HR: 1.20; P=0.72), LVI (HR: 0.89; P=0.85), and PNI (HR: 1.98; P=0.48) were not associated with a worse OS.  Similarly, recurrence-free survival was also not affected by high-risk microscopic features (all P>0.05). 

Conclusion: Over three-fourths of patients with resected stage II colon cancer possess at least one high-risk microscopic feature.  The presence of these high-risk features did not impact short-term OS or RFS. Further studies on OS and RFS among patients with stage II colon cancer and high-risk microscopic features are warranted.
 

06.10 Frailty as a Predictor of Acute Mortality among Stage IV Cancer Patients with Bowel Obstruction

S. B. Bateni1, F. J. Meyers2, R. J. Bold1, A. R. Kirane1, D. J. Canter3, R. J. Canter1  1University Of California – Davis,Surgical Oncology,Sacramento, CA, USA 2University Of California – Davis,Hematology/Oncology,Sacramento, CA, USA 3Ochsner Clinic,Urology,New Orleans, LOUSIANA, USA

Introduction: Patients with disseminated malignancy (DMa) frequently present with acute surgical conditions. Bowel obstructions are especially common, with rates as high as 28-51% for gastrointestinal and gynecologic cancers. However, surgical intervention performed on this at-risk population is associated with increased rates of morbidity and mortality as high as 44% and 11% respectively. Our objective was to determine the effect of frailty on predicting the risk of acute morbidity and mortality in DMa patients undergoing surgical management of bowel obstruction.

Methods: Patients with DMa and primary diagnosis of bowel obstruction were identified from the 2007 to 2012 American College of Surgeons National Surgical Quality Improvement Program with corresponding ICD-9 codes. The previously validated modified frailty index (mFI) score was calculated for each patient. Univariate and multivariate standard parametric and nonparametric statistical analyses including χ² and logistic regression were utilized to identify predictors of 30-day overall morbidity, Clavien IV/V morbidity and mortality.

Results: We identified 1,928 DMa patients with bowel obstruction who underwent small bowel resection (22.0%, n=424), large bowel resection (20.5%, n=395), celiotomy or lysis of adhesions (22.8%, n=440), gastric (3.7%, n=71) or other abdominal operation (31.0%, n=598). 11.9% (n=181) were identified as frail with mFI≥0.27. Emergency operations were common at 34.6% (n=668). Preoperative impaired functional status and diagnoses of systemic inflammatory response syndrome (SIRS) and sepsis/septic shock were also frequent at 21% (n=404), 17.8% (n=341) and 6.6% (n=127) respectively. Rates of 30-day overall morbidity, ClavienIV/V morbidity, and mortality were 35.8% (n=690), 12.2% (n=235), and 14.8% (n=285) respectively. Predictors of overall and Clavien IV/V morbidity identified on multivariate analysis included impaired functional status, low albumin, SIRS, sepsis and septic shock, and emergency operations. Frailty was significant on univariate, but not multivariate analyses, for overall and Clavien IV/V morbidity (p>0.05). Frailty was identified as a significant predictor for 30-day mortality on univariate (OR=3.56, 95%CI 2.59-5.15) and multivariate analysis (OR=1.73, 95CI 1.09-2.75) in addition to low albumin, SIRS, and ASA 4/5.

Conclusion: Frailty is a predictor of acute mortality after surgery for bowel obstruction among DMa patients. In patients with a terminal malignancy, the goals of surgical therapy for symptom palliation need to be balanced against adverse outcomes, particularly mortality. Risk assessment is essential. The mFI, therefore, may be used as an additional tool by surgeons to determine risk of acute mortality for DMa patients with bowel obstruction. It is important to recognize that the mFI was not a predictor of acute morbidity and, consequently, further research is needed to optimize decision making for this at-risk population.

06.09 Understanding Effects of Age Race & Socioeconomic Status on Outcomes in Patients with Colon Cancer

O. O. Osuchukwu1, V. Pandit1, S. W. Mbugua1, J. Jandova1,2, A. Cruz1, V. N. Nfonsam1  1University Of Arizona,Surgery,Tucson, AZ, USA 2University Of Arizona,Institute For Cellular Transplant,Tucson, 85724, USA

Introduction:

Differences in outcomes among patients based on demographic and racial profile are well established. However; the impact of these differences on patient outcomes with colon cancer (CC) remains unclear. We hypothesized that racial and demographic profile is associated with adverse outcomes among patients with CC.

Methods:
National estimates for patients with CC were extracted from the National Inpatient Sample (NIS) database (2011). Patients were stratified based on age, race and insurance status. Outcome measures were: hospital length of stay (LOS), complications, and mortality. Regression analysis was performed after adjusting for age, gender, race, Charlson co-morbidity index (CCI), and type of surgical intervention.  

Results:
A total of 37,513 patients with CC were analyzed. The mean age was 68.3±13.9 years, 51.1% were females and the mean CCI was 2 [2-3]. Sixty-five and half percent of patients were white and 67.3% were Medicare/Medicaid insured. The overall mortality rate was 4.6%. Mortality rate significantly increased (p=0.04) with increasing age. Native Americans had the highest mortality rate and complication rate among all races. On regression analysis, increasing age (OR: 1.6 [1.1-3.1]), being non-white (OR: 1.3 [1.2-2.7]), and Medicare/Medicaid insurance status (OR: 1.2 [1.05-3.8]) were independently associated with mortality. Additionally, increasing age (OR: 1.9 [1.3-4.4]) and non-white race (OR: 1.4 [1.05-2.9]) were associated with increased in-hospital complication.

Conclusion:

Demographic, racial and socio-economic disparities are prevalent among patients with CC with worse outcomes among old and non-white patients. Native American patients with CC have worse outcomes among all races. Further assessing the causes for these disparities may help mobilization of resources and improve outcomes among patients with CC.
 

06.08 Compliance of Endocrine Therapy and Outcomes Following Lumpectomy Without Adjuvant Radiation

M. G. Shah-Khan1, L. Woldanski1, A. L. Kong1  1Medical College Of Wisconsin,Surgical Oncology,Milwaukee, WI, USA

Introduction:

Patient adherence to prescribed endocrine therapy for breast cancer is variable in both the preventative and adjuvant setting.  For patients undergoing breast conserving surgery (BCS), there is data to support forgoing radiation therapy in older women with estrogen receptor positive (ER+) disease.  We sought to determine the rate of initiation and adherence to endocrine therapy in patients undergoing lumpectomy without radiation therapy, and determine the rate of recurrence in these patients.

Methods:

A retrospective review was performed to identify patients treated within our institution from 2000-2014.   Patients included were aged 60 and older and underwent BCS for ER+ invasive cancer (T1-T2) or DCIS, and did not undergo adjuvant radiation therapy.   Chart review was performed to determine the rate of initiation and subsequent adherence to endocrine therapy.   Recurrence and survival information was also evaluated.

Results:

A total of 206 patients were evaluated, with mean age of 76.  Mean follow up was 49 months.  One hundred forty three patients underwent BCS for invasive cancer, and 63 patients for DCIS.  Of the patients with invasive cancer, 89% (n=127) were T1, and 11% (n=16) were T2.  Seventy percent were lymph node negative, 7% were lymph node positive, and 23% had no lymph nodes evaluated.  Sixty eight percent (n=97) initiated endocrine therapy with either tamoxifen or an aromatase inhibitor.  Forty nine patients (30%) adhered to treatment for greater than 2 years, with 19% completing at least 4 years of treatment.   A total of 14 (10%) of patients had a recurrence in the study period.  Twelve patients (8%) had an ipsilateral locoregional recurrence, and 1 patient had a distant recurrence.  One patient developed a contralateral primary invasive breast cancer during follow up.  Twenty six percent of patients (n=37) died during the follow up period, with one death related to metastatic breast cancer.

Patients undergoing lumpectomy for DCIS had a lower rate of initiation of therapy, however rate of compliance over time was not significantly different. Only 35% of DCIS patients (n=22) initiated endocrine therapy, compared to 68% of patients with invasive cancer (p<0.0001).  Twenty percent of patients (n=13) completed at least 2 years of therapy.  Thirteen percent (n=8) of patients completed at least 4 years of therapy.  Four patients (6%) developed a recurrence, 2 with ipsilateral DCIS, and 2 with contralateral primary breast cancers (1 DCIS, 1 invasive).  Three patients (4.7%) died during the study period, with no breast cancer related deaths. 

Conclusion:

In older patients undergoing BCS for T1-T2 ER+ in situ or invasive breast cancer who forego adjuvant radiation, initiation of endocrine therapy is higher in patients with invasive cancer than with DCIS, however compliance decreases in both groups over time.  A low incidence of recurrence and breast cancer related mortality was seen in both groups of patients. 

06.07 The Prognostic Significance of Adrenocortical Carcinomas Identified Incidentally

K. K. Rossfeld1, N. Saunders2, T. Tran13, Q. Duh9, J. Mansour8, S. Maithel2, C. Solorzano10, T. Wang4, J. Glenn4, E. Levine11, S. Weber6, A. Salem6, R. Fields5, G. Poultsides13, T. Pawlik1, J. Phay1, L. A. Shirley1  1Ohio State University,Department Of Surgery,Columbus, OH, USA 2Emory University School Of Medicine,Department Of Surgery,Atlanta, GA, USA 3Johns Hopkins University School Of Medicine,Department Of Surgery,Baltimore, MD, USA 4Medical College Of Wisconsin,Department Of Surgery,Milwaukee, WI, USA 5Washington University,Department Of Surgery,St. Louis, MO, USA 6University Of Wisconsin,Department Of Surgery,Madison, WI, USA 7University Of California – San Diego,Department Of Surgery,San Diego, CA, USA 8University Of Texas Southwestern Medical Center,Department Of Surgery,Dallas, TX, USA 9University Of California – San Francisco,Department Of Surgery,San Francisco, CA, USA 10Vanderbilt University Medical Center,Department Of Surgery,Nashville, TN, USA 11Wake Forest University School Of Medicine,Department Of Surgery,Winston-Salem, NC, USA 12New York University School Of Medicine,Department Of Surgery,New York, NY, USA 13Stanford University,Department Of Surgery,Palo Alto, CA, USA

Introduction:
Adrenal tumors, including adrenocortical carcinomas (ACC), are often identified incidentally on imaging, being diagnosed as an “incidentaloma”.   Little is known regarding the difference in prognosis among patients who have an incidental ACC versus those patients with ACC who present with signs or symptoms.

Methods:
Patients who underwent resection of ACC at one of 13 institutions between January 1993 and December 2014 were identified.  ACC tumors were categorized as incidentalomas versus symptomatic adrenal tumors.  Patients without data fields needed for the current study were excluded.  Data on patient age, gender, race, body mass index (BMI), tumor size, tumor weight, presence of metastases, and margin status were collected and analyzed according to incidental versus non-incidental ACC category.  Clinical variables were analyzed using Chi-square, Fisher Exact, or independent T-test as appropriate.  Kaplan-Meier curves for overall (OS) and recurrence-free survival (RFS) were analyzed using log-rank testing.  Cox regression was utilized to analyze potential differences in OS and RFS among relevant clinical variables.

Results:
Among 232 evaluable patients with ACC, 100 (43.1%) were diagnosed with an incidental ACC while 132 (56.9%) patients presented with symptoms/signs.  Clinical and pathological features including age, gender, race, BMI, nodal status, tumor size, tumor weight, and surgical margin status were all comparable among incidental versus non-incidental ACC patients (all p>0.05). However, patients with incidentalomas were more likely to have a T1/T2 tumor (55.8% vs. 33.9%, p<0.01) and were less likely to have metastatic disease at presentation (13.1 % vs. 23.6%, p=0.031).  Patients with an incidental ACC had a better median RFS (29.4 months) compared with patients with a non-incidental ACC (12.5 months, p=0.020).  The improved RFS among patients with incidental ACC tumors persisted when RFS was stratified by the presence of metastasis (p=0.034), but not by T stage (p= 0.29).  Among patients who initially presented with an incidentaloma, those who had tumors that were later noted to be hormonally active on further work-up had a shorter RFS compared with patients with non-functional tumors (8.8 vs. 47.9 months, p=0.002). 

Conclusion:
Patients with resected ACC who had tumors that were identified incidentally had an improved RFS compared with patients who presented with symptoms or signs.  This difference in RFS was likely related to a lower T-stage on presentation.  Patients with incidentalomas that were hormonally active had a shorter RFS than those with non-functional incidentalomas, highlighting potential prognostic importance of evaluating hormonal secretion in asymptomatic patients.
 

06.06 Residual Lymph Node Metastasis After Initial Surgical Treatment Of Differentiated Thyroid Cancer

O. Brown1, J. Miller1, N. Al-Attar1, G. Shaughness1, N. Rosculet1, A. Avram1, D. Hughes1  1University Of Michigan,Ann Arbor, MI, USA

Introduction:  Differentiated thyroid cancer (DTC) is treated with thyroidectomy and removal of malignant lymph nodes identified preoperatively. Despite attempts to resect regional metastatic disease, residual malignant lymph nodes are often found on diagnostic and/or post-therapy radioiodine scans at the time of radioactive iodine treatment. The objective of this study is to identify the most common locations of and reasons for residual lymph node metastases following initial surgical treatment of DTC.

Methods:  In this retrospective study, we reviewed the charts of 352 patients with high-risk DTC treated at the University of Michigan from 2007 to 2014. Postoperatively, all patients underwent pre-ablation 131-Iodine scans with SPECT/CT. The laterality of the primary tumor and the presence and location of nodal metastases were noted. We compared the location of the nodal metastases with cervical lymph node levels that were dissected to determine the reason for residual nodal metastases (incomplete node dissection vs. omission of node dissection in that compartment due to failure to identify nodal involvement preoperatively).

Results: A total of 146/352 (41.48%) patients with high-risk DTC were found to have residual lymph node metastases on diagnostic 131-I SPECT/CT following initial surgical treatment. These 146 patients had a combined total of 218 nodal metastases. Relative to the primary tumor, 71.56% (n=156) were ipsilateral, 22.02% (n=48) were contralateral, and 6.42% (n=14) were undefined, meaning they were classified as central neck (level VI/VII) without a designation of laterality. Cervical lymph node levels VI, III, and II were found to have the greatest frequencies of residual metastases, with 33.94% (n=74), 22.94% (n=50), 18.81% (n=41), respectively. Levels I and V had the lowest frequencies of metastases, with 0.46% (n=1) and 0.00% (n=0), respectively. Residual metastases occurred because of an incomplete lymph node dissection in 72 patients (49.32%), a missed diagnosis in 55 patients (37.67%), or a combination of the two in 19 patients (13.01%).

Conclusion: The surgical management of high-risk DTC should include complete nodal dissection in all involved compartments. Particular attention should be given to complete dissection in levels VI, III, and II, especially ipsilateral to the primary tumor, as these are prevalent areas of residual nodal metastasis. Efforts to improve pre-operative diagnostic techniques and to refine lymph node dissection practices may reduce the incidence of residual nodal metastasis.

06.05 Cancer Independently Worsens and Increases Variability of Short-term Surgical Outcomes

I. L. Leeds1, J. E. Efron1, N. Ahuja1, E. R. Haut1, F. M. Johnston1  1Johns Hopkins University School Of Medicine,Department Of Surgery,Baltimore, MD, USA

Introduction:
There is a growing consensus that common surgical prediction models do not adequately predict surgical outcomes for cancer surgery patients. The purpose of this study was to examine the comparative performance of these models in benign versus malignant gastrointestinal surgery populations to assess their utility as a risk-counseling tool for providers and patients.

Methods:
The American College of Surgeons’ National Surgical Quality Improvement Program’s (NSQIP) 2014 participant use file was queried for patients undergoing elective surgery with a primary procedure code of a major colon, pancreas, or stomach resection. All patients with a diagnosis of gastrointestinal cancer were compared against those without using Chi-square and Wilcox-Mann-Whitney tests. Multivariable logistic regression was performed to identify independent predictors of mortality and morbidity.

Results:
We identified 37,809 cases (16,322 malignant, 21,487 benign; 30,789 colectomies, 5,963 pancreatectomies, 1,057 gastrectomies). All of the following reported differences were statistically significant. The gastrointestinal cancer surgery population was disproportionately male, older than 65, non-white, and less functionally independent. Major comorbidities more prevalent in the non-cancer surgery group included chronic steroid use, preoperative sepsis, and active smoking. Comorbidities more common in the cancer surgery population included disseminated malignancy, diabetes, hypertension, dyspnea, and COPD.

Cancer surgery patients had a longer length of stay (+0.9 days), higher mortality rate (0.9% vs. 0.5%), higher complication rate (26.9% vs. 21.2%), higher total number of complications per surgery (0.5 vs. 0.3), broader variation in total number of complications (σ2= 1.0 vs. 0.8), higher readmission rate (11.4% versus 10.6%), higher pneumonia incidence (2.5% vs. 1.9%), higher reintubation rate (2.1% versus 1.3%), extended ventilator-days (1.6% vs. 1.1%), more kidney injuries (1.4% vs. 0.9%), more in-hospital cardiac arrests (0.7% vs. 0.4%), more blood transfusions (12.0% vs. 6.4%), and more blood clots (1.4% vs. 1.1%).

NSQIP probability variables performed similarly for complications in cancer and non-cancer patients (r= 0.32 vs. 0.31) but underperformed for mortality (r= 0.24 vs. 0.14). Multivariable regression controlling for predictors and procedure type demonstrated that a diagnosis of cancer requiring surgery independently confers an increased risk of death of 34.4% (p=0.034) and 12.0% (p<0.001) increased risk of additional complications as compared to patients with benign disease.

Conclusion:
NSQIP prediction models less effectively evaluate the risk of death in cancer patients as compared to patients undergoing similar resections for benign disease. Furthermore, a diagnosis of cancer independently increases the risk of complication and death from surgical resection. Additional counseling of short-term outcomes uncertainty may be needed.
 

06.04 Oncologic Outcomes Associated with Robotic Pancreatic Resections

P. Briceno1, R. Shridhar3, J. Huston1, S. Kucera2, K. Meredith1  1Florida State University College Of Medicine/Sarasota Memorial Health Care System,Gastrointestinal Oncology,Sarasota, FL, USA 2Florida State University College Of Medicine,Endoscopic Oncology,Sarasota, FL, USA 3University Of Central Florida,Radiation Oncology,Orlando, FL, USA

Introduction:  Surgery remains a key component of treatment for resectable pancreatic adenocarcinoma. Mortality rates have dropped dramatically over the past several decades with improvements in preoperative care, intraoperative surgical techniques and instrumentation, as well as post-operative care. However, improving outcomes from pancreatic resection through minimally invasive surgical approaches has gained interest. While there is widespread adoption of both laparoscopic and robotic resections for cancers of the left pancreas the demanding technical requirements of performing a minimally invasive pancreaticoduodenectomy (RPD) and prolonged learning curve have proven to difficult for most. There are several reports of operative outcomes for patients undergoing robotic pancreatic resections, however the survival in these patients has not been investigated. 

Methods:  Utilizing the National Cancer Database we identified patients who underwent pancreatic resection. We then stratified by operative approach. Outcomes of patients were then compared between open(OP), robotic(RP) and laparoscopic(LP) approaches.  Baseline univariate comparisons of patient characteristics were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests as appropriate. Pearson’s Chi-square test was used to compare categorical variables. Survival was evaluated on the basis of time from date of diagnosis to date of death or censoring. Unadjusted survival analyses were performed using the Kaplan-Meier method comparing survival curves with the log-rank test. All statistical tests were two-sided and α (type I) error <0.05 was considered statistically significant. 

Results: We identified N = 17,738 patients who underwent pancreatic resection with a median age of 66 (18-90) years.  There were 14,568 open, 2,739 laparoscopic, and 431 robotic. There were 7943 open whipples (OW) and 3455 open distal pancreatectomies (ODP).  Within the minimally invasive approaches there were 1123 (41%) laparoscopic whipples (LW), 1616 (59%) laparoscopic distal pancreatectomies (LDP), 122 (28.3%) robotic whipple (RW), and 309 (71.7%) robotic distal pancreatectomies (RDP). The 30-day mortality between OP, LP and RP was 3.5%, 2.8%, and 2.6%, p=0.1 however the 90-day mortality was 7.2%, 5.8%, and 4.6%, p=0.004. R0 resections were performed in 78.5% OP, 83.7% LP, and 86.3% RP, p<0.001. The median survival was 30.1 months OP, 37.7 months LP, and 52.3 months RP, p<0.001. However, RP and LP had higher T1 and T2 as well as node negative patients p<0.001 and p<0.001 respectively.  Conversions to open occurred in 24.2% LP and 13.9% RP, p<0.001. Within the LDP and RDP there were 351 (21.7%) and 36 (11.7%) conversions, p<0.001. The LW and RW demonstrated 308 (27.4%) and 29 (23.8%) conversions, p=0.4. 

Conclusion: Our analysis indicates that robotic assisted pancreatic resections are at least equivalent in oncologic outcomes to standard open approaches.  Robotic techniques resulted in fewer conversions to open compared to laparoscopic approaches particularly in the distal pancreatectomy cohorts. 

 

06.03 Gene-expression Classifier Testing in the Management of Cytologically Indeterminate Thyroid Nodules.

M. Affi1, B. Javorsky1, T. Yen1, K. Doffek1, B. Hunt1, P. Tolat1, T. Carroll1, T. Giorgadze1, A. Carr1, D. Evans1, T. Wang1  1Medical College Of Wisconsin,Milwaukee, WI, USA

Introduction:  Up to 30% of thyroid nodules evaluated by fine needle aspiration (FNA) are indeterminate on cytology. Use of a 167 gene mRNA-based gene-expression classifier (GEC) test has been shown to have a high negative predictive value for benign nodules and a 40% malignancy rate for GEC-suspicious nodules. The aim of this study was to determine the rate of malignancy in thyroid nodules indeterminate on initial cytology that underwent repeat FNA in anticipation of GEC testing. 

Methods:  This is a retrospective review of all patients with thyroid nodules with indeterminate cytology ('atypia/follicular cells of unknown significance’ or ‘suspicious for follicular neoplasm’) and who underwent GEC testing between 10/12-5/16. Prior to GEC testing, repeat FNA was performed and cytology results were reviewed by an independent cytologist; only indeterminate samples underwent GEC testing. Patients with GEC-benign nodules were recommended for surveillance. Patients with re-classified cytology that was 'suspicious for malignancy' or GEC-suspicious nodules were referred for thyroidectomy. The rate of clinically significant malignancy (>1cm) in patients undergoing thyroidectomy was determined, based on both initial cytology and results of GEC testing.

Results: 89 patients met inclusion criteria. Independent review of cytology yielded 35 (39%) benign, 48 (54%) indeterminate, 2 (2%) suspicious for malignancy, and 4 (5%) non-diagnostic samples. Of the 35 patients with benign cytology, 2 (6%) underwent thyroidectomy with benign final histopathology. The 2 patients with suspicious cytology had a clinically significant papillary thyroid cancer on final histopathology. Of the remaining 52 samples, 46 had sufficient mRNA for GEC analysis; 17 (37%) were GEC-benign and 29 (63%) were GEC-suspicious. None of the patients with GEC-benign lesions have had surgery; to date, 6 (35%) patients have had no changes on follow-up ultrasound. Of 26 patients with GEC-suspicious samples who underwent thyroidectomy, 18 (69%) had benign pathology, 5 (19%) had a clinically significant malignancy, and 3 (12%) patients had an incidental malignancy. Overall, 32 (36%) patients underwent thyroidectomy; based on the original institutional cytological diagnosis of ‘indeterminate,’ the rate of clinically significant malignancy was 22% (7/32).  

Conclusion: Of the 89 patients with indeterminate initial cytology, repeat FNA with cytological review and GEC testing altered the management of 52 (58%) patients. The clinically significant malignancy rate for GEC-suspicious thyroid nodules was 19%, much lower than the reported 40% rate and equivalent to our institutional rate of malignancy in patients with indeterminate nodules who underwent surgery. Further follow-up of nonsurgical patients with GEC-benign nodules is required to determine the true benefit of GEC testing in patients with cytologically indeterminate thyroid nodules at our institution.

 

06.02 Novel MicroRNA Expression Patterns of Breast Cancer to Predict Survival

T. Kawaguchi1, L. Yan2, Q. Qi2, S. Liu2, K. Takabe1  1Roswell Park Cancer Institute,Breast Surgery, Department Of Surgical Oncology,,Buffalo, NY, USA 2Roswell Park Cancer Institute,Department Of Biostatistics & Bioinformatics,Buffalo, NY, USA

Introduction:
MicroRNAs (miRNAs) are small non-coding RNAs that exert its functions by regulating expression of their target genes. Dysregulations of miRNAs are related with breast cancer (BrCa).The purpose of this study was to classify BrCa with miRNAs expression patterns to predict survival utilizing The Cancer Genome Atlas (TCGA).

Methods:
Both clinical and miRNA-seq data enrolled in TCGA dataset were retrieved from the GDC data portal for analyses, and were evaluate by hierarchical clustering based on bioinformatics analysis. We also evaluate clinical relevance including prognostic analysis based on the novel subclasses using the Cox proportional hazard model. 

Results:
Of 1097 cases enrolled in TCGA dataset, 1052 caseswere used for miRNAs expression data and survival analysis. We devided the cases into “short” (died within 3 years after diagnosis), “long” (lived longer than 5 years), and the others. We identified that 15 miRNAs (let-7a-1, miR-106a, miR-17, miR-184, miR-18a, miR-193a, miR-19a, miR-20a, miR-20b, miR-362, miR-4661, miR-500a, miR-766, miR-92a-1, miR-93) were significantly differently expressed between the long and short group. With the expression pattern of these 15 miRNA, the patients were classified into three clusters. Of the 15 miRNAs, we conducted additional feature selection in a multivariate Cox proportional hazard model, and three miRNAs remain after model selection (miR-106a, miR-766, and miR-93). We generated a risk scoring model with the expression of the three miRNAs based on Cox proportional hazard model. We found that the patients with the high score significantly associated with poor outcome. 

Conclusion:
We demonstrated a novel concept that microRNA expression patterns of BrCa can predict worse survival.
 

06.01 Hospital Variation in Neoadjuvant Therapy for T1-2 Pancreatic Cancer: Short and Long-term Outcomes

M. A. Healy1, S. Shubeck1, W. Burns1, T. L. Frankel1, H. Nathan1  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA

Introduction:  The benefit of neoadjuvant therapy for resectable pancreatic cancer (PanCa) is controversial, and its use varies significantly between centers. It is unknown whether neoadjuvant therapy practices are associated with short- and long-term patient outcomes across institutions. We sought to evaluate whether institutions that routinely use neoadjuvant therapy achieve superior aggregate outcomes for PanCa patients. 

Methods:  Using the National Cancer Data Base Participant User File, we identified patients with non-metastatic T1-2 PanCa diagnosed from 2006-2013. Hospitals were stratified into quintiles based on risk- and reliability-adjusted rates of neoadjuvant therapy use in resected patients (including chemotherapy and/or radiation). Post-operative and survival outcomes were compared between hospitals using neoadjuvant therapy frequently (Neo-Hi) vs infrequently (Neo-Lo).

Results: We identified 20,646 patients with median age 72 years and 25% T1 tumors. Among 815 treating hospitals, adjusted rates of neoadjuvant therapy varied almost 30-fold (2.9%-83%). Patients at Neo-Hi vs Neo-Lo hospitals had higher readmission rates (8.8% vs 7.4%; P<0.01) but similar 30-day mortality (6.0% vs 5.8%;P=0.6). Neo-Hi vs Neo-Lo hospitals had lower surgical margin positivity (17% vs 21%; P<0.001) and node positivity (56% vs 63%; P<0.001). Resected patients at Neo-Hi vs Neo-Lo hospitals had marginally improved adjusted overall survival at 2 years (48% vs 51%) but not at 5 years (22% vs 22%) (overall HR 0.92, P<0.05). When patients who received systemic therapy but did not ultimately undergo resection were included, there was also no difference in survival (HR 0.98, P=0.3).

Conclusion: Hospitals that use neoadjuvant therapy more frequently in T1-2 PanCa demonstrate lower rates of nodal and margin positivity in resected patients. When patients receiving systemic therapy without ultimately undergoing resection are included, there is no survival difference across hospitals, although these patients may be spared surgical morbidity. Institutional practices regarding neoadjuvant therapy for PanCa do not result in improved aggregate outcomes.