44.19 Incidence of Occult Carcinoma in Patients Undergoing Surgical Intervention for Benign Thyroid Disease

Posted on January 26, 2017

A. Franco1, J. C. Farrá1,2, O. Picado Roque1, A. R. Marcadis1, R. Teo1, W. Ouyang1, S. Liu1, J. I. Lew1,2  1University Of Miami,Endocrine Surgery,Miami, FL, USA 2Sylvester Comprehensive Cancer Center,Miami, FL, USA

Introduction:  The incidence of occult thyroid malignancy in patients undergoing surgery for benign thyroid conditions has been shown to be higher than expected.  There may be a risk of missing thyroid carcinomas in patients who do not undergo surgical management of their disease. This study examines the association between benign indication for total thyroidectomy and the finding of thyroid cancer on final pathology.

Methods:  A retrospective study of prospectively collected data of 761 patients undergoing partial or complete thyroidectomies at a tertiary referral center was performed. Data collected included demographic characteristics, reason for referral, symptoms, preoperative imaging, FNA cytology, and final pathology results. The reason for referral was stratified into benign and malignant disease. Final pathology was examined for both malignancy in the index nodule as well as incidental malignancy independent of the index nodule.  Multivariate logistic regression was used to assess the effect of reason for referral on the odds of having cancer on final pathology.

Results: Of 761 patients who underwent thyroidectomy, 301 were referred for benign disease and 460 for malignancy. Of 301 cases referred for benign disease, 89 were found to have malignancy on final pathology (30%). These 89 cases included 33 that had a malignant index nodule, 34 with incidental malignancy, and 22 in which both an index nodule malignancy and incidental malignancy were found on final pathology.   The rates of malignancy according to reason for referral were as follows: 10% (4/40) for Grave’s Disease, 32% (60/189) for non-toxic multinodular goiter (MNG), 49% (18/37) for non-toxic solitary nodule, 19% (4.21) for toxic MNG, and 21% (3/14) for substernal goiter.  Of patients with benign thyroid disease and underlying malignancy, 73% had follicular variant papillary thyroid cancer (PTC) (n=65), 16% classical variant PTC (n=14), 2% tall cell variant PTC (n=2), and 2% diffuse sclerosing variant PTC (n=2), 5% follicular carcinoma (n=4), 1% medullary thyroid cancer (n=1), and 1% anaplastic thyroid cancer (n=1) on final pathology.  On multivariate analysis, patients with non-toxic MNG had an increased odds of incidental thyroid malignancy on final pathology (OR= 2.7, p <0.01). Patients with Grave’s Disease had a decreased risk of thyroid malignancy on final pathology (OR= 0.19, p <0.01).

Conclusion: Patients operated on for benign thyroid disease have clinically significant rates of underlying malignancy on final pathology.  Careful evaluation and counseling by a surgeon is necessary in the management of these patients. Total thyroidectomy remains an important surgical option for patients with multinodular goiters.

 

44.18 Progressive Radiographic Findings After Breast Conserving Surgery and Intraoperative Radiation

Posted on January 26, 2017

K. Reno5, A. Kuritzky1, B. Mooney2, W. Sun1, J. Zhou3, Z. Ma3, M. C. Lee1, C. Laronga1  1Moffitt Cancer Center,Breast Surgery,Tampa, FLORIDA, USA 2Moffitt Cancer Center,Radiology,Tampa, FLORIDA, USA 3Moffitt Cancer Research Center,Biostatistics,Tampa, FLORIDA, USA 5University Of South Florida,College Of Medicine,Tampa, FLORIDA, USA

Introduction: Breast cancer treatment utilizing Intraoperative radiation (IORT) concurrently with breast conserving surgery (BCT) is an evolving therapy. The IORT cavity changes radiographically on short time follow up (<1yr), but data regarding long-term (>1yr) changes is sparse. Our aim was to assess long-term imaging findings following BCT/IORT.

Methods: An IRB-approved, retrospective chart review of cases from a single-institution, BCT + IORT prospective database between 01/11-02/14 was conducted. Clinical-pathologic reports and surveillance (physical and radiographic) exams at 6 months, and yrs 1-5 were recorded. Ultrasound (US) of the lumpectomy cavity was performed at 6 months postop as standard operating procedure. All US data was re-reviewed by an independent breast radiologist. Demographics are summarized using descriptive statistics. Statistical analysis was performed using Wilcoxon rank-sum and Kruskal-Wallis Fisher exact test.

Results: During the study period, 114pts underwent BCT/IORT. The median age was 71yrs [range 51-88]; median tumor size was 1.0cm [range 0.2-3.5cm]. The median follow up was 3.25yrs [range 0.25-5.4]. US > 1 yr was performed for symptoms or mammographic changes. Of the 65pts that received US at 6 months 63(96.9%) pts had a seroma with 14(21.5%) being symptomatic; Of the 43 pts that received US, at 1yr follow-up 38(88.4%) had seroma with 7(16.3%) symptomatic. Of the 7 pts that received a 3yr US, 1(14.3%) was symptomatic and of the 4 that received a 4yr US, 3(75%) were symptomatic. In all patients, size of seroma decreased overtime from 10.7cm3 at 6 months, to 8.5cm3 at 1yr, to 5.75cm3 at 2yrs, and to 5.3cm3 at 3yrs. Of the 106pts with 6 month mammogram, the most common findings were post lumpectomy changes in 68(64.2%) pts. BiRADS scores range from 1–5 with a median of BiRADS 2 at 6 months, 2 at yr 1, 2 at yr 2, and 2 at yrs 3-5. Percentage of pts with BiRADS 3 progressively decreased from 16(15.1%) at 6 months to 5(5.2%) at 2yrs and to 0 by 4 yrs. In this time frame, 7pts were found to have in-breast recurrences; 6 were detected mammographically and one by punch biopsy of skin lesion. Median time from surgery to recurrence was 36 months (range 12-65). In these 7 pts, mammographic findings were BiRADS 2-3 at 6months followed by a new abnormality designated as a BiRADS 4b or 4c finding at yrs 1-5.

Conclusion: In pts receiving BCT/IORT, seroma cavity size decreased over time with the largest change at 2yrs as seroma resolved. Mammographic BiRADs stabilized by yr 2 with the majority of pts receiving a score of 2 for benign findings after yr 2. IORT did not interfere with mammographic interpretation, especially local recurrence findings.

 

44.17 Utilizing the Modified Frailty Index to Predict Morbidity for Retroperitoneal Sarcoma Resections

Posted on January 26, 2017

J. S. Park1, S. B. Bateni1, A. R. Kirane1, R. J. Bold1, D. J. Canter2, R. J. Canter1  2Ocshner Clinic,Urology,New Orleans, LOUSIANA, USA 1University Of California – Davis,Sacramento, CA, USA

Introduction: Preoperative risk assessment is important and critical as the population ages with increasing number of comorbidities.  The modified frailty index (mFI) is an important method to risk-stratify surgical patients that has been validated for general surgery and selected surgical subspecialties.  However, there are currently no data assessing the efficacy of the mFI to predict acute morbidity and mortality in patients undergoing surgery for retroperitoneal sarcoma (RPS).

Method: Using the American College of Surgeons’ National Surgical Quality Improvement Program from 2007 to 2012, we performed a retrospective analysis of patients identified by ICD-9 and CPT codes with a diagnosis of retroperitoneal neoplasm who underwent surgical resection. We calculated mFI consistent with published methods and patients were categorized as frail when mFI≥0.27. Univariate and multivariate analyses including χ² and logistic regression was utilized to identify predictors of 30-day overall morbidity, Clavien IV/V morbidity and mortality.

Results: We identified 950 patients with the diagnosis of retroperitoneal neoplasm undergoing surgical resection. Tumors were stratified by size ≤5cm (19.7%, n=187), 5–10 cm (17.5%, n=166), and >10cm (62.8%, n=597). The average age was 59 (SD±13) and majority of patients were female (50.6%, n=480) and Caucasian (79.6%, n=755) with independent functional status (97.6%, n=923). Only 36 (4.9%) were classified as frail. Few had undergone preoperative chemotherapy (5.2%, n=38) and radiotherapy (7.2%, n=52). Rates of 30-day overall morbidity, Clavien IV/V morbidity, and mortality were 22.3% (n=212), 6.0% (n=57), and 1.1% (n=10) respectively. Frailty was a significant predictor of Clavien IV/V morbidity on univariate (OR = 4.99, 95%CI = 2.03-12.24, p<0.001) and multivariate (OR 3.16, 95%CI = 1.01-9.87, p<0.01) analysis. As the mFI increased, there was an increase in the Clavien IV/V complications (p<0.01).  However, frailty was not a predictor of overall morbidity and mortality (p>0.05). Impaired functional status alone was the significant predictor of mortality on univariate (OR = 32.18, 95%CI = 8.39-123.40, p<0.001) and multivariate analysis (OR = 25.49, 95%CI =2.68-242.78, p<0.01). Tumor size and preoperative chemotherapy or radiotherapy were not associated with 30-day overall and Clavien IV/V morbidity and mortality on univariate analysis with p>0.20 and, therefore, excluded in the multivariate analysis.

Conclusion: Our data demonstrate that the vast majority of patients undergoing RPS resections are healthy with very few frail patients identified. Although frailty was a significant predictor of serious complications, it was not significantly predictive of overall morbidity and mortality. Our findings suggest that impaired preoperative functional status may be of greater utility than mFI to risk-stratify patients undergoing RPS resections.

44.16 Assessing the Impact of Graves Disease on the Incidence of Thyroid Cancer

Posted on January 26, 2017

K. N. Edwards1, N. Bhutiani1, A. R. Quillo1  1University Of Louisville,Department Of Survery, Division Of Surgical Oncology,Louisville, KY, USA

Introduction: Graves’ Disease is the most common autoimmune disorder in the United States and is the underlying cause of 50-80% of cases of hyperthyroidism.  To date, there has been no true consensus as to the risk thyroid nodules pose for thyroid cancer in patients with Graves’ disease.  This study aimed to assess the prevalence of thyroid carcinoma in patients with Graves’ disease who underwent thyroidectomy at our institution and identify possible predictive factors of thyroid carcinoma in those with Graves’.

Methods: Patients undergoing thyroidectomy at our institution between 2011 and 2016 who enrolled in our prospectively collected research database were identified and classified according to whether they carried a diagnosis of Graves’ disease and then whether malignancy was present on final pathology.  They were then compared along demographic parameters, results of pre-operative ultrasound and fine needle aspirate (FNA) findings, and final pathology.  Two-tailed student t-tests were performed to determine the significance of any noted differences between comparison groups.

Results: A total of 363 patients met inclusion criteria. Of these, 113 patients underwent thyroidectomy for Graves’ disease, and 250 for other reasons.  Overall, the incidence of thyroid cancer in these two groups did not differ significantly (p=0.16).  Among patients with Graves disease, 16 (14%) had evidence of malignancy on final pathology while 97 had benign findings.   However, in patients with both Graves’ disease and the presence of thyroid nodules on preoperative ultrasound, 31% of patients were determined to have thyroid cancer upon final pathology evaluation.   In addition, patients with Graves’ disease were less likely to have undergone pre-operative FNA than patients without Graves’ (p<0.0001). Finally, among patients who underwent ultrasound, those with Graves’ disease and cancer who were more likely to have nodules than those who had Graves’ disease alone (75% vs. 42%, p=0.016).

Conclusion: Patients with Graves’ disease who had evidence of malignancy on final pathology are more likely to have nodules visible on ultrasound than those without any evidence of malignancy.  A more frequent use of FNA in patients with Graves’ disease undergoing thyroidectomy who have nodules visible on ultrasound should be considered given the correlation between presence of nodules and malignancy to potentially optimize decisions regarding extent of surgical intervention. In addition, the overall rate of malignancy in patients with both Graves’ disease and nodules in our database was 31%, higher than the overall risk of malignancy in multinodular goiter in the general public.  For this reason, surgical treatment over other treatment options for Graves’ should be strongly considered in all patients with both Graves’ disease and nodules.

 

44.14 Utilization of Molecular Profiling in Colorectal Cancer: a Tertiary Cancer Center’s Experience

Posted on January 26, 2017

N. Nweze1, F. Zih1, B. Luo1, E. Sigurdson1, S. Reddy1, E. Lamb1, J. M. Farma1  1Fox Chase Cancer Center,Surgical Oncology,Philadelphia, PA, USA

Introduction:

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer death in the United States in both men and women.  CRC has been shown to be a heterogeneous disease with genetic variations.  Next-generation sequencing (NGS) is commonly being used to further elucidate treatment options in CRC patients.  Our goal was to review our experience using NGS in CRC patients at a tertiary cancer center.

Methods:

We performed an IRB-approved, retrospective study of 100 patients with the diagnosis of CRC who underwent molecular profiling within our institution between January 2006 and January 2016.  Our in house NGS platform evaluates for 50 commonly mutated cancer genes.  We tested patients with recurrent CRC or metastatic disease. We then identified the most commonly mutated genes, as well as patterns of clinical outcomes including recurrence rates and survival outcomes.

Results:

We evaluated 100 patients with CRC, 65% were male and 79% were White.  The mean age at diagnosis in years was 59.2 ± 12.9 (SD).  100% had adenocarcinoma.  11% had mucinous subtype, 6% had signet ring cell subtype and 2% had mixed subtype with neuroendocrine features.  The mean BMI was 27.7 ± 6.3 (SD) and 59.7% had a smoking history.  68% had colon CA and 32% had rectal CA.  10% had no mutations, 27% had 1 mutation, 32% had 2 mutations, 19% had 3 mutations, 7% had 4 mutations and 5% had 5 mutations.  The most common mutations were p53 (n=64), APC (n=37), and KRAS (n=35).  Other mutations detected were: PIK3CA (n=13), SMAD4 (n=12), BRAF (n=6), PTEN (n=4), CTNNB1 (n=3), NRAS (n=3), GNAS (n=2), FBXW7 (n=2), FGFR3 (n=2), STK11 (n=2), ABL1, AKT1, CDKN2A, IDH1, KDR, PDGFRA, PTPN11, (n=1).  59% had stage 4 disease; 88.1% of these patients had at least 1 mutation, 59.3% had 2 or more mutations and 11.8% had no mutations.  79.6% had unresectable stage 4 disease (n=47); 87.2% of these patients had at least one mutation, 57.4% had 2 or more mutations and 12.7% did not have any mutations.  20.3% had stage 4 disease that was amendable to R0 resection (n=12); 100% of these patients had at least 1 mutation and 66.6% had 2 or more mutations.  53% presented with resectable disease and 96.2% of these patients had a recurrence within 2 years (n=51).  94.1% had at least 1 mutation, 66.6% had 2 or more mutations and 5.8% had no mutations.  Median length of follow up was 2.2 years.  14% had no evidence of disease at the time of follow up, 61% were alive with disease and 25% had died of the disease.

Conclusion:

The majority of CRC patients with metastatic disease or recurrent disease who underwent NSG at our institution were found to have at least one mutation.  P53, APC and KRAS were the most commonly mutated genes.  NGS was used as an adjunct to guide treatment therapy, however it remains to be seen whether the information provided by molecular profiling changes recurrence or survival outcomes.

 

44.15 Outcomes Following Resection of Hepatocellular Carcinoma in the Absence of Cirrhosis

Posted on January 26, 2017

R. H. Lewis1, D. M. Bittenbinder1, T. O’Brien2, E. S. Glazer1, M. D. Fleming1, S. W. Behrman1, D. Shibata1, J. L. Deneve1, P. V. Dickson1  1University Of Tennessee Health Science Center,Division Of Surgical Oncology, Department Of Surgery,Memphis, TN, USA 2University of Tennessee Health Science Center,Department Of Pathology,Memphis, TN, USA

Introduction:
Hepatocellular Carcinoma (HCC) most commonly arises in the setting of cirrhosis and generally has a poor prognosis.  HCC occasionally occurs in non-cirrhotic livers, however, outcomes for these patients are not extensively documented.  We report an institutional experience of hepatectomy for HCC in the absence of cirrhosis.

Methods:
We performed of retrospective review of patients with HCC in non-cirrhotic livers who underwent partial hepatectomy. Patients with fibrolamellar tumors and a hepatic fibrosis score >3 were excluded.  Clinical data was evaluated to identify factors impacting recurrence free (RFS) and overall survival (OS).    

Results:
We identified 40 patients who underwent partial hepatectomy for HCC in the absence of cirrhosis over a 10-year period. Median age was 62 years (23-83) and 65% were male.  A solitary tumor was present in 57% with tumor size ranges of 0-4.9cm (25%), 5-9.9cm (40%), and ≥10cm (35%). Non-tumor bearing liver demonstrated hepatic fibrosis scores of F0 in 19 (47.5%), F1 in 12 (30%), F2 in (15%), and F3 in 3 (7.5%) patients.  Steatosis was absent in 7 (17.5%), minimal in 31 (77.5%), and moderate in 2 (5%) patients. Hepatitis B and C were documented in 2 and 8 patients, respectively. R0 resection (>1mm margin) was achieved in 32 patients (80%) and major hepatectomy (≥ 3 contiguous segments) was performed in 26 (65%). Overall 30-day post-operative complications occurred in 37.5% and 90-day mortality was 10%.  Thirty-five patients had available follow up data, median 28 months (5-125). Among this cohort, 1- and 5-year RFS was 62% and 39% and 1- and 5-year OS was 83% and 53%. For stage I, II, III patients, 5-year RFS and OS were 48%, 34%, 10% (p=0.056) and 60%, 38%, 12% (p=0.025), respectively.  On univariate analysis, 5-year RFS and OS were worse for patients with a disrupted/absent vs intact tumor capsule (24% vs 74%, p=0.034; 31% vs 83%, p=0.018); presence of vascular invasion vs none (19% vs 40%, p=0.030; 30% vs 45%, p=0.067), elevated vs normal alkaline phosphatase (Alk Phos) levels (7% vs 49%, p=0.002; 10% vs 55%, p=0.017); and elevated vs normal aspartate aminotransferase (AST) levels (20% vs 50%, p=0.081; 23% vs. 63%, p=0.041). RFS was worse for patients with a tumor size ≥10cm (15%) vs 0-4.9cm (58%) and 5-9.9cm (25%), p=0.042.  Alpha fetoprotein levels, viral hepatitis, fibrosis score, hepatic steatosis, higher tumor grade, presence of satellite lesions, and R1 resection did not portend worse RFS or OS in the current study.

Conclusion:
Patients with HCC in the absence of cirrhosis often present with large (>5cm) tumors.  Although 5-year OS was 53%, even patients with early stage disease demonstrate high recurrence rates.  Disruption or absence of a tumor capsule, tumor size ≥10cm, presence of vascular invasion and elevated Alk Phos and AST were associated with decreased RFS and/or OS.  Future analyses of a larger cohort of patients will better define other potential prognostic factors.

44.13 Risk stratification using PT-INR to albumin ratio in patients with hepatocellular carcinoma

Posted on January 26, 2017

K. Haruki1, H. Shiba1, N. Saito1, T. Horiuchi1, Y. Shirai1, Y. Fujiwara1, K. Furukawa1, T. Sakamoto1, T. Gocho1, T. Misawa1, K. Yanaga1  1The Jikei University School Of Medicine,Department Of Surgery,Tokyo, TOKYO, Japan

Introduction:  Liver function in patients with hepatocellular carcinoma (HCC) is generally graded according to the Child-Pugh (C-P) system.  However, some variables in the C-P grade are subjective.  We developed a novel objective score; prothrombin time-international normalized ratio to albumin ratio (PTAR).  The aim of this study is to evaluate the prognostic value of PTAR in patients with HCC after hepatic resection.

Methods:  The study comprised 199 patients who had undergone elective hepatic resection for HCC between January 2003 and December 2014.  We retrospectively investigated the relation between PTAR and disease-free as well as overall survival and assessed hepatic functional reserve using the PTAR in comparison with C-P grade.

Results: The optimal cut-off level of the PTAR was 0.288.  In multivariate analysis, the independent and significant predictors of cancer recurrence consisted of HCV infection (p=0.011), pT4 or pT3 (p<0.001) and PTAR ≥ 0.0288 (p=0.024), while the independent and significant predictors of poor overall survival were pT4 or pT3 (p<0.001) and PTAR ≥ 0.0288 (p<0.001).  ICGR15 (p=0.007), C-P score (p<0.001) and serum AFP (p=0.037) positively correlated with high PTAR.  Pathological liver cirrhosis (p<0.001), postoperative ascites (p=0.039) and postoperative liver failure (p=0.040) in patients with high PTAR were significantly greater than their counterparts.  In patients with C-P grade A, PTAR ≥ 0.0288 was significantly associated with worse disease-free survival (p=0.024) and overall survival (p=0.030).

Conclusion: The PTAR may be an independent and significant indicator of poor long-term outcome in patients with HCC after hepatic resection.  The PTAR may reflect liver function, and patients with C-P grade A could be stratified by the PTAR.
 

44.12 Clinically Significant Cancer Rates in Incidentally Discovered Thyroid Nodules by Routine Imaging.

Posted on January 26, 2017

O. Picado Roque1, J. C. Farrá1,2, S. Liu1, W. Ouyang1, R. Teo1, A. Franco1, M. Gunder1, J. I. Lew1,2  1University Of Miami,Division Of Endocrine Surgery,Miami, FL, USA 2Sylvester Comprehensive Cancer Center,Miami, FL, USA

Introduction:  With the widespread use of diagnostic imaging modalities, incidentally discovered thyroid nodules are often identified when evaluating patients for unrelated reasons.  If the risk of underlying thyroid cancer in such incidental nodules is clinically significant, further evaluation and treatment becomes imperative. This study evaluates the malignancy rate of incidentally detected thyroid nodules by imaging compared to non-incidental thyroid nodules in surgical patients.

Methods:  A retrospective review of prospectively collected data of 811 patients who underwent thyroidectomy at a tertiary referral center was performed. Patients who had incidentally discovered thyroid nodules by imaging studies unrelated to thyroid disease were stratified according to age, sex, FNA results, imaging modality, cytological features, and final histopathology. Malignancy rates were determined for incidentally discovered thyroid nodules. Categorical variables were compared among groups using chi-square or Fisher’s exact tests as appropriate.  Student’s t-tests were used to compare continuous measures.

Results: Of 811 patients, 12.1% of patients (n=98) had incidental thyroid nodules detected by imaging, whereas 87.9% of patients (n=713) were non-incidental. Of patients with incidentally discovered thyroid nodules, 66.3% (n=65) had malignancy whereas 56.4% (n=402) of patients with non-incidental thyroid nodules had malignancy on final pathology. Overall, 14% (65/467) of patients with malignancy identified on final pathology were discovered incidentally by routine imaging. The most common imaging modality leading to detection included in descending order: non-thyroid ultrasound (n=31, 31.6%), CT (n=28, 28.6%), MRI (n=23, 23.5%), PET (n=15, 15.3%), and chest x-ray (n=1, 1%). Rates of malignancy according to imaging modality were as follows: 71% for ultrasound, 57% for CT, 61% for MRI, 86.7% for PET. Of patients with incidental thyroid nodules harboring malignancy, 52% had follicular variant papillary thyroid cancer (PTC) (n=31), 20% classical variant PTC (n=12), 14% tall cell variant PTC (n=8), and 14% diffuse sclerosing variant PTC (n=8) on final pathology. Patients with incidentally discovered malignant thyroid nodules were more likely to have lymphovascular invasion compared to non-incidental malignant thyroid nodules (53% vs. 41%, p=0.07). Extrathyroidal invasion was identified in 23% (n=15) of patients with malignant incidental thyroid nodules.

Conclusion: Incidentally discovered thyroid nodules by imaging represent an important group of surgical patients with clinically significant rates of underlying malignancy. Furthermore, a higher than expected proportion of such patients demonstrated aggressive histological features on final pathology. Patients with incidentally discovered thyroid nodules by imaging should undergo appropriate evaluation and counseling for further surgical treatment.

 

44.11 Outcomes Associated with Esophagectomy: Results from a Large Prospectively Maintained Database

Posted on January 26, 2017

D. Lee1, P. Briceno2, R. Shridhar3, S. Kucera4, K. L. Meredith2  1Florida State University College Of Medicine,Sarasota, FL, USA 2Florida State University College Of Medicine/Sarasota Memorial Health Care System,Gastrointestinal Oncology,Sarasota, FL, USA 3University Of Central Florida,Radiation Oncology,Orlando, FL, USA 4Florida State University College Of Medicine/Sarasota Memorial Health Care System,Endoscopic Oncology,Sarasota, FL, USA

Introduction:  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.  We report our experience with esophageal cancer patients undergoing esophagectomy from a large prospectively maintained database. 

Methods:  A prospectively managed esophagectomy database was queried for patients undergoing esophagectomy 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 856 patients who underwent esophagectomy with a mean age of 64 ± 10 years, mean BMI of 28.6 ± 6, and a mean follow up of 48 ± 13 months. There were 717 (83.8%) males and 139 (16.2%) females. Neoadjuvant therapy was administered in 543 (63.4%) patients. There were 475 (55.5 %) open Ivor Lewis (OIL), 69 (8.1%) open trans-hiatal (OTH), 10 (1.2%) open Mckeown, 95 (11.0%) minimally invasive esophagectomies (MIE) via Ivor Lewis approach (MIE IVL), 63 (7.4%) MIE TH and 144 (16.8%) robotic assisted Ivor Lewis esophagectomies (RAIL). There were 504 (58.8%) open esophagectomies and 302 (35.2%) MIE. Complications occurred less frequent in patients undergoing RAIL and MIE IVL:  145 (30.5%) OIL, 28 (40.6%) OTH, 28 (29.5%) MIE IVL, 31 (49.2%) MIE TH, and 34 (23.6%) RAIL (p=0.003). Pulmonary complications also occurred less frequently in RAIL and MIE IVL: 72 (15.2%) OIL, 12 (17.4%) OTH, 18 (28.6%) MIE TH, 8 (8.4%) MIE IVL, and 10 (6.9%) RAIL, p<0.001. Anastomotic leaks were less common in patients who underwent IVL either open or minimally invasive compared to trans-hiatal approaches: 23 (4.8%) OIL, 4 (4.2%) MIE IVL, 4 (2.8%) RAIL, versus 9 (13.0%) OTH, 4 (6.3%) MIE TH, p=0.03. There were 13 (1.5%) mortalities and this did not differ among techniques, p= 0.6. Oncologic quality as indicated by R0 resections and mean lymph node harvest were improved in patients undergoing RAIL: 449 (94.7%) and10±6 OIL, 62 (89.9%) and 8±5 OTH, 60 (96.8%) and 9±6 MIE TH, 86 (93.5%) and 14±7 MIE IVL, and 144 (100%) and 20±9 RAIL, p=0.04 and p=0.001. Median length of hospitalization was 9 days in both RAIL and MIE IVL and 10 days in all other groups, p=0.2. 

Conclusion: We report our experience with varying approaches to esophageal resections from a large esophagectomy database.  Minimally invasive and robotic Ivor Lewis techniques demonstrated substantial benefits in post-operative complications.  Oncologic outcomes similarly favor MIE IVL and RAIL.  Pulmonary outcomes were not reduced by trans-hiatal approaches.

 

44.10 High Perioperative Morbidity and Mortality in Patients with Malignant Nonfunctional Adrenal Tumors

Posted on January 26, 2017

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

Introduction: Adrenal gland tumors are categorized into those that produce excess hormones (functional) and those that do not (nonfunctional). Both functional and nonfunctional adrenal tumors can be further subdivided by benign and malignant pathology. Malignant nonfunctional adrenal tumors are rare, with definitive diagnosis often made by final pathology. Furthermore, the morbidity and mortality associated with surgical treatment of such uncommon tumors remains uncertain. This study compares the perioperative in-hospital outcomes after adrenalectomy in patients with benign and malignant nonfunctional adrenal tumors.

Methods: A retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample database (2006-2011) to identify surgical patients hospitalized for adrenal tumors. Patients who underwent unilateral open or laparoscopic adrenalectomy for nonfunctional adrenal tumors were further subdivided into benign and malignant groups based on final pathology. Patient demographics, socioeconomic and clinical factors, comorbidities, and perioperative complications were evaluated by univariate and risk-adjusted multivariate logistic regression. Data were analyzed using two-tailed Chi-square and t-tests.

Results: Of 28,339 patients who underwent unilateral adrenalectomy for nonfunctional adrenal tumors, 75% (n=21,279) had benign adenomas, while the remaining 25% (n=7,060) had malignancy on final pathology. Patients with malignant nonfunctional adrenal tumors were more likely to be younger in age (46 vs 54 years; p<0.01) and men (61.6 vs 44.6%; p<0.01) compared to patients with benign nonfunctional adrenal tumors. Patients with malignant nonfunctional adrenal tumors were more likely to suffer intraoperative complications including vascular (7.1 vs 3.8%; p<0.01) and splenic injury (5.6 vs 2.1%; p<0.01), postoperative complications including hematoma (3.6 vs 2.0%; p<0.01), shock (1.1 vs 0.5%; p<0.01), acute kidney injury (3.1 vs 2.5%; p<0.01), venous thromboembolism (1.5 vs 0.6%; p<0.01), and pneumothorax (1.6 vs 0.9%; p<0.01), as well as have higher rates of blood transfusion (18.5 vs 7.0%; p<0.01), longer hospital stay (5.9 vs 4.2 days; p<0.01) and higher hospital charges (59,529 vs $45,152; p<0.01) compared to their benign counterparts. Finally, patients with malignant nonfunctional adrenal tumors had a significantly higher in-hospital mortality compared to patients with benign nonfunctional adrenal tumors (1.0 vs 0.4%; p <0.01).

Conclusion: Patients with malignant nonfunctional adrenal tumors have significantly higher perioperative morbidity and mortality compared to their benign nonfunctional counterparts. Men younger than 50 years of age with nonfunctional adrenal tumors have an increased risk for underlying malignancy. Such patients should be counseled and medically optimized in preparation for adrenalectomy, and surgeons should remain vigilant in preventing perioperative complications.

44.09 Adjuvant Radiation Provides Limited Survival Benefit After R1 Resections For Pancreatic Head Cancer

Posted on January 26, 2017

N. R. Suss1, M. S. Talamonti1,2, D. S. Bryan2, C. Wang1, K. M. Kuchta1, S. J. Stocker1, D. J. Bentrem3, K. K. Roggin2, D. J. Winchester1,2, R. Marsh1,2, R. A. Prinz1,2, M. S. Baker1,2  1NorthShore University HealthSystem,Department Of Surgery,Evanston, IL, USA 2University Of Chicago,Department Of Surgery,Chicago, IL, USA 3Feinberg School Of Medicine,Department Of Surgery,Chicago, IL, USA

Introduction: The benefit of adding radiation to adjuvant systemic chemotherapy in patients that have undergone a margin positive resection for early stage pancreatic cancer (PDAC) has not been well established. 

Methods: We queried the National Cancer Database (NCDB) for 2004 through 2012 to identify patients with pathologic stage I-II PDAC of the pancreatic head who underwent pancreaticoduodenectomy and had a microscopic positive margin on final pathology (R1 resection). Kaplan-Meier, multivariable and cox regression modeling were employed to identify factors associated with radiation use and compare overall survival for patients receiving adjuvant chemotherapy with radiation (CRT) to those receiving adjuvant chemotherapy alone (ACT).  Patients receiving neoadjuvant therapy and those who did not receive adjuvant chemotherapy were excluded.

Results: 1,310 patients met inclusion criteria. 255 (19.5%) were lymph node negative (Stages IA, IB, IIA) and 1,055 (80.5%) were node positive (Stage IIB). 897 (68.5%) patients received CRT, while 413 (31.5%) received ACT. Multivariable stepwise logistic regression identified younger age (OR 2.310, 95% CI [1.515, 3.521]), treatment in New England (OR 7.915, 95% CI [3.369,18.595]), and negative nodal status (OR 1.797, 95% CI [1.286, 2.511]) as independently associated with use of CRT.  Cox modeling adjusting for age, sex, race, comorbid disease state, socioeconomic status (SES), insurance status, facility type and volume, surgery type, vascular abutment, pathological T stage, and nodal status, identified High SES (HR 0.717, 95% CI [0.609, 0.846]) and use of CRT (HR 0.828 95% CI [0.726, 0.944]) as independently associated with improved overall survival. Charlson score of one (HR  1.226 95% CI [1.069-1.406]) and node positivity (HR 1.547 95% CI [1.317, 1.817]) were independently associated with higher risk of mortality. Cox modeling stratified by stage demonstrated the benefit of radiation to be statistically significant in node positive patients only.  Node positive patients undergoing CRT demonstrated a median survival of 17.1 months vs. 14.8 months for node positive patients undergoing ACT (p=0.001). In patients who were lymph node negative, there was no difference in overall survival with radiation (21.9 vs. 23.3 months, p=0.457) [Figure 1].

Conclusion: Addition of radiation to adjuvant chemotherapy confers a limited survival benefit over treatment with chemotherapy alone in patients having an R1 resection for lymph node positive pancreatic head cancer.  Radiation offers no benefit for patients undergoing an R1 resection for disease that is node negative. Randomized trials are needed to better identify subgroups of PDAC patients for whom benefits of radiation justify the known risks. 

 

44.08 Impact of Neoadjuvant Radiation and Chemotherapy on Perioperative Complications Following Whipple

Posted on January 26, 2017

T. Tan1, C. McDaniel1, W. W. Zhang1, D. Rybin2, G. Doros2, Q. Chu1  1Louisiana State University Health Sciences Center,Depatment Of Surgery,Shreveport, LA, USA 2Boston Medical Center,Boston, MA, USA

Introduction: We evaluated the outcomes of patients undergoing pancreaticoduodenectomy who received neoadjuvant radiation therapy and chemotherapy for pancreatic cancer.

 

Methods: Using the National Surgical Quality Improvement Program dataset (2005-2012), we identified and examined 10,217 pancreaticoduodenectomy using the ICD-9 and CPT codes. Patients were divided into two groups based on whether they received neoadjuvant radiation and chemotherapy. Outcomes evaluated were perioperative mortality and morbidity. Multivariable logistic regression was used to examine association between neoadjuvant therapy and perioperative outcomes adjusting for possible confounders.

 

Results: There were 10,217 pancreaticoduodenectomys in this study cohort with 488 patients (5%) receiving neoadjuvant therapy prior to surgery. Patients who were treated with neoadjuvant therapy had significant higher history of >10% weight lost prior to surgery (26% vs. 18%, p<.001), chronic steroid therapy (3% vs. 2%, p=.03), and significantly longer operative time (443±140 vs. 373±128 minutes, p<.001). Although perioperative survival was similar between two cohorts, those treated with neoadjuvant therapy had significantly higher risk of surgical site infection (SSI) (14% vs. 10%, p=.002), thromboembolism (5% vs. 3%, p=.03) but lower risk of pneumonia (3% vs. 5%, p=.10).  In multivariable analysis, neoadjuvant therapy was associated with increased risk of SSI (OR 1.4, 95% CI 1, 1.8, p=.02), but lower risk of pneumonia (OR 0.5, 95% CI 0.3, 0.8, p=.007).

Conclusion: Patients who received neoadjuvant radiation therapy and chemotherapy have significant higher risk of surgical site infection following pancreaticoduodenectomy for pancreatic cancer. Further studies are required to evaluate appropriate role of neoadjuvant therapy in patients undergoing surgical treatment for pancreatic cancer. 

44.07 Complete Response to Neoadjuvant Chemoradiation Does Not Increase Morbidity After Esophagectomy.

Posted on January 26, 2017

A. M. Brown1, D. Giugliano1, F. Palazzo1, E. L. Rosato1, N. R. Evans1, C. R. Lamb1, D. A. Levine1, A. C. Berger1  1Thomas Jefferson University,Department Of Surgery,Philadelphia, PA, USA

Introduction:
Neoadjuvant chemoradiation (nCRT) followed by definitive esophagectomy has become a mainstay of treatment for stage two and three esophageal cancer. It has been demonstrated in rectal cancer that a complete response to nCRT is a predictor of anastomotic leak, as well as post-operative morbidity and mortality. We hypothesized that a complete treatment effect after nCRT may negatively affect anastomotic leak rate and post-operative morbidity and mortality.

Methods:
A retrospective review of all patients who underwent esophagectomy following nCRT for esophageal cancer between January 2000, and June 2016 was completed. The patients were stratified by their response to preoperative chemoradiation: no change or upstage (group 1), partial response (group 2), or a complete response (group 3), based on final surgical pathology. The postoperative courses of all patients were reviewed for anastomotic leak, respiratory failure defined as ventilator dependence greater than 48 hours, re-intubation, or acute respiratory distress syndrome (ARDS), as well as any pulmonary complication. All complications were categorized using a modification of the Clavien-Dindo classification. Statistical significance was calculated using a one-sided ANOVA test. 

Results:
There were 215 patients who underwent esophagectomy for esophageal cancer. The average age was 61 (range 31 to 84). Open esophagectomy was performed in 91 patients, and 124 underwent minimally invasive esophagectomy. With regards to neoadjuvant treatment, 78 patients (36%) had no change or a pathological upstage, 69 (32%) had a partial response, and 68 (32%) had a complete response. Rates of anastomotic leak were 14.1% in group 1, 8.7% in group 2, and 17.6% in group 3 (p=0.306). Rates of respiratory failure were similar—21.8%, 23.2%, and 23.5% respectively (p=0.965). Grade 3 or higher complication rates were 29.5%, 31.9%, and 30.9% respectively (p=0.952). There were no major differences in the frequency of any pulmonary complication (41.0%, 43.5%, 35.3%, p=0.607), or peri-operative mortality (7.7%, 5.8%, and 7.4% (p=0.895)). 

Conclusion:
There are no significant differences in complications and anastomotic leak based on pathologic response to nCRT.  Esophagectomy after nCRT is not compromised by a complete pathologic response.
 

44.06 Prognostic Nomogram for Patients with Operable Pancreatic Cancer Treated with Neoadjuvant Therapy

Posted on January 26, 2017

S. Jeong1, M. Aldakkak1, K. Ahn2, C. Huang3, K. K. Christians1, B. A. Erickson4, P. S. Ritch5, B. George5, D. B. Evans1, S. Tsai1  4Medical College Of Wisconsin,Radiation Oncology,Milwaukee, WI, USA 5Medical College Of Wisconsin,Hematology Oncology/Dept Of Medicine,Milwaukee, WI, USA 1Medical College Of Wisconsin,Surgery,Milwaukee, WI, USA 2Medical College Of Wisconsin,Biostatistics,Milwaukee, WI, USA 3University Of Wisconsin, Milwaukee,Biostatistics/Joseph J. Zilber School Of Public Health,Milwaukee, WI, USA

Introduction: American Joint Committee on Cancer (AJCC) TNM staging system provides population based estimates of survival based on pathologic variables.  For patients with pancreatic cancer (PC), survival estimates were generated from patients who have undergone surgery with or without postoperative therapy. Increasingly, preoperative (neoadjuvant) therapy followed by surgery is being utilized in patients with PC in recognition of the high risk of disease recurrence and the inability to consistently deliver adjuvant therapy after pancreatectomy. Whether the AJCC staging system accurately predicts survival among patients who have received neoadjuvant therapy is unclear. We assessed the survival discrimination of the AJCC staging system for patients with PC who have received neoadjuvant therapy and surgery, and developed a novel prognostic nomogram using clinical variables.

Methods: Clinical data and survival outcomes from patients with PC who completed neoadjuvant therapy and surgery at a single institution were collected. Survival at 1-, 2-, and 3-years from the date of restaging after neoadjuvant therapy and surgery were used for the purpose of nomogram construction. Concordance index (c-index) and calibration plots were used to assess predictive accuracy. The nomogram was developed using multivariable Cox proportional hazards model. Clinical stage was defined at the time of diagnosis and patients were categorized as having resectable or borderline resectable disease. Postoperative carbohydrate antigen 19-9 (CA19-9) was measured at the first restaging visit after surgery.

Results: Data was available for 167 patients with resectable and borderline resectable PC. The concordance indices (c-index) for 1-, 2-, and 3- years using the AJCC staging system were 0.57, 0.55, and 0.56, respectively. Clinical stage (HR:2.31; 95%CI:1.48-3.63) and postoperative CA19-9 levels (HR: 2.14; 95%CI:1.38-3.34) were the strongest prognostic factors. A parsimonious nomogram (Figure 1) including clinical stage, postoperative CA19-9, and age predicted 1-, 2-, and 3- year survival with c-indices of 0.66, 0.66, and 0.66, respectively. Calibration plots showed good fitness between observed and predicted probabilities. A combined nomogram using clinical stage, postoperative CA19-9, age, and AJCC stage demonstrated c-indices for 1-, 2-, and 3-years of 0.68, 0.67, and 0.67, respectively.

Conclusion: AJCC staging system poorly discriminates survival for patients who have received neoadjuvant therapy and surgery. A prognostic nomogram utilizing clinical stage and postoperative CA19-9 levels provides more accurate survival prediction than the AJCC model.  External validation will be performed to assess the generalizability of the nomogram. 

44.05 Overall Survival after Resection for Retroperitoneal Sarcoma at Academic vs. Community Centers

Posted on January 26, 2017

N. G. Berger1, J. P. Silva1, K. K. Christians1, S. Tsai1, T. Gamblin1  1Medical College Of Wisconsin,Surgery, Division Of Surgical Oncology,Milwaukee, WI, USA

Introduction:  Surgical resection remains the curative therapy for retroperitoneal sarcoma (RPS). Data recently published shows a correlation between improved outcomes for complex oncologic operations and treatment at academic centers. For large retroperitoneal sarcomas, surgical resection can be complex and require multidisciplinary care. The present study hypothesized that survival rates vary between treating center for patients undergoing resection for retroperitoneal sarcoma.

Methods:  Patients with all-stage and all-size retroperitoneal sarcomas who underwent surgical resection were identified from the National Cancer Database (2004-2013). Treating centers were categorized as Academic Cancer Centers (ACC) or Community Cancer Centers (CCC). OS was analyzed by log-rank test and graphed using Kaplan-Meier method.

Results: A total of 5,106 patients were identified. Median age of diagnosis was 63. The majority of patients (58.2%, n=2,970) patients underwent resection at an ACC.  Improved median OS was seen at ACCs across all stages compared to CCCs (79.1 months vs. 64.3 months; p=0.004). ACCs exhibited a higher rate of R0 resection (51.2% vs. 44.1%, p<0.001). No difference between cohorts was seen for 90-day mortality or 30-day readmission rates, though 30-day mortality at CCCs following resection did trend toward significance (1.9% vs. 2.9%, p=0.061). On Cox univariate regression, age, sex, ethnicity, Charlson Comorbidity Score, tumor size, tumor grade, and treating facility were identified as significant factors. Following multivariate regression, treatment at an academic center was associated with a significant hazard ratio (HR) for survival (HR= 0.91, IQR 0.82-1.00, p=0.045).

Conclusion: Resection for RPS performed at ACC is associated with improved survival compared to CCC, and an improved HR for survival on multivariate regression. This suggests that site of care plays a role in patient outcomes.

 

44.04 Near infrared perfusion assessment of gastric conduit in minimally invasive Ivor Lewis esophagectomy

Posted on January 26, 2017

B. G. Dalton1, A. A. Ali2, Z. T. Awad1  1University Of Florida-Jacksonville,Surgery,Jacksonville, FL, USA 2Wayne State University,Surgery,Detroit, MI, USA

Introduction:

Anastomotic leak and conduit necrosis can be devastating complications following Ivor Lewis esophagectomy. Conduit ischemia is the leading cause of graft necrosis and anastomotic leak. Near infrared imaging (NIR) using IndoCyanine Green (ICG) allows for real time assessment of tissue perfusion.  We theorized that the use of intraoperative NIR during laparoscopic minimally invasive Ivor Lewis esophagectomy (MIE) would allow for resection of a greater portion of gastric conduit which may reduce leak rate.

Methods:

After IRB approval retrospective analysis of a prospectively collected data from 2014-2015 of 40 consecutive MIE was performed.  All operations were performed for esophageal cancer by a single surgeon at a tertiary referral center. Intravenous ICG and laparoscopic NIR (Pinpoint, Novadaq, Canada) were used to visualize and assess gastric conduit perfusion for the most recent 20 patients in the study (NIR group). Extended conduit resection was performed if ischemia was present on NIR.  The non-NIR group was composed of the 20 MIE cases immediately prior to the advent of NIR use in our practice. Comparative analysis was performed using student t test for continuous variables and Fishers exact for binary variables.  Statistical significance is defined as P ≤ 0.05.

Results:

No differences were found between the 2 groups with regard to age, gender, BMI, clinical stage, pathologic stage, or comorbidities.  Comparing non-NIR to NIR groups, no statistically significant differences were found in overall complication rate (55% vs 40%, p=0.53), reoperation within the same admission (5% vs 10%, p=1), 90 day readmission (10% vs 10%, p=1) and 90 day reoperation (10% vs 5%, p=1). NIR resulted in extended level of proximal conduit resection in 30% (6/20) in the NIR group. Two patients in NIR group developed anastomotic leak (2/20) while no patients in the non-NIR group were found to have leaks (p=0.48). Both leaks were in patients that had additional conduit resection after NIR technology was used to assess conduit perfusion. Endoscopic stent placement was used to manage both leaks, and operative drainage or repair were not required.  One mortality related to graft necrosis was noted in the non-NIR group, while there were 0 mortalities in the NIR group. (p=1.0).

Conclusion:

Although near infrared angiography plays a vital role in assessment of tissue perfusion, in our study its use did not result in reduction of anastomotic leak rate. However, this technology did allow for additional resection of ischemic portions of the gastric conduit.  This extended resection potentially prevented extensive conduit necrosis.  Larger studies are needed to validate the use of this novel technology.

44.03 Pilot Study of SAVI SCOUT® to Localize Non-Palpable Breast Lesions to Reduce Re-excision

Posted on January 26, 2017

R. Shirley1, P. Peddi1, S. Ahmed1, Q. D. Chu1  1Louisiana State University Health Sciences Center-Shreveport,Surgery,Shreveport, LA, USA

Introduction: Wire localization (WL) is standard preoperative procedure to localize non-palpable breast lesions.  The SAVI SCOUT® guidance system is an FDA-approved medical device that uses non-radioactive electromagnetic wave technology and serves as an alternate to WL technique.  The purpose of the study is to compare the re-excision rates between WL and SAVI SCOUT® and assess the ease of performing such a technique by surgical trainees.   

Methods: We performed an IRB approved retrospective chart review of all women undergoing WL from 2011-2015 and compared them to women undergoing SAVI SCOUT® technique from 2015-2016. Re-excision rates, weights of the final specimens, and rate of detection by surgical trainees were calculated. Statistical t-tests and chi square tests were used.  P-value ≤0.05 was considered as statistically significant. 

Results:Of the 116 WL breast cancer biopsies performed, 43 required re-excision (37%).  Of the 26 SAVI SCOUT® performed, 17 were malignant; of these 17, only 2 required re-excision (11.8%; P=0.04).  This translates to a reduction of 68.2% with SAVI SCOUT®.  The average specimen weight for the WL group was 63g versus 55g for the SAVI SCOUT® group (P=0.38.  The average margin width was 2.7 mm for the WL versus 3.0mm for the SAVI SCOUT® (P=0.43). Surgical residents were successful in localizing the lesions in 25 out of 26 (96%) patients using SAVI SCOUT® technique.   

Conclusion:The re-excision rate was significantly lower with SAVI SCOUT® and can easily be done by surgical residents. Given its advantages, SAVI SCOUT® should be considered over WL technique.  

 

44.02 Risk Factors for Post-operative Complications After Lymph Node Dissection for Melanoma

Posted on January 26, 2017

B. Sunkara1, S. Diljak1, R. D. Kramer1, R. J. Strobel1, D. J. Mercante1, J. S. Jehnsen1, J. F. Friedman1, A. Durham1, T. Johnson1, M. S. Cohen1  1University Of Michigan,Department Of Surgery,Ann Arbor, MI, USA

Introduction:  While the literature looking at complications after lymphadenectomy for melanoma is fairly robust, the root cause analysis of risk factors contributing to those complications has not been as well studied and often reported only in smaller case series. The purpose of this study is to analyze in the largest melanoma lymphadenectomy cohort to date the risk factors that have significant association with development of post-operative complications outside of lymphedema or lymphocele. 

Methods:   This is a retrospective review of a prospectively collected database cohort of consecutive patients having either an axillary lymph node dissection (ALND) or inguinal lymph node dissection (ILND) at our institution since January 2005. Complications were defined as occurring in the first 30 days after surgery and not including lymphocele or lymphedema. Exclusionary criteria for this study include patients with bilateral dissections or those having both an ILND and an ALND. Patients were stratified according to presence or absence of complications associated with their surgery and analyzed for associated risk factors using Chi Squared tests, and Student T tests with significance defined as p< 0.05. 

Results:  Of the 524 patients who were included in our study: 175 patients (33.4%) had post-op complications. Complications were more likely to occur in females compared to males (38.5% vs 30.1%; p=0.046), those having a right-sided procedure compared to the left (38.1% vs 28.3%; p=0.017), and those having an ALND vs. ILND (50.4% vs 20.9%; p= <0.001). Other risk factors significantly correlating with post-op complications included pre-operative hypertension (39.6% with vs 29.0% without; p=0.011), or patients with a readmission within 30 days after surgery (84.2% of those readmitted had a post-op complication as the reason for re-admission vs 24.8% readmitted without a post-op complication; p=<0.001). Interestingly having a micrometastasis in the sentinel lymph node biopsy (vs. macroscopic disease and having no positive nodes on the dissection each decreased the chance of developing a post-op complication (p=0.003). Patients who developed lymphedema or a lymphocele after their surgery were also more likely to develop another post-operative complication (p=0.002 and <0.001 respectively).  Finally the number of lymph nodes removed did not correlate with any significant increased risk of developing post-operative complications. 

Conclusion:   This is the largest series to date evaluating risk factors for post-operative complications following ALND and ILND for melanoma.  Risk factors correlating with higher post-op complication rates included being female, right sided operations, pre-op HTN, or development of lymphedema or lymphocele. Protective factors included microscopic disease in the sentinel node or lack of additional positive nodes in the lymphadenectomy specimen. These factors are important and should be included in pre-operative discussions with patients having ALND and ILND for metastatic melanoma. 

 

44.01 Greater Lymph Node Retrieval and Lymph Node Ratio Impacts Survival in Resected Pancreatic Cancer

Posted on January 26, 2017

K. A. Mirkin1,2, C. S. Hollenbeak1,2, J. Wong2  1Penn State University College Of Medicine,Department Of Public Health Sciences,Hershey, PA, USA 2Penn State University College Of Medicine,Department Of Surgery,Hershey, PA, USA

Introduction:
Surgical resection is the mainstay of pancreatic cancer treatment, however, the ideal lymphadenectomy remains unsettled.  Several meta-analyses have concluded that extended lymphadenectomies do not impact survival.  The objective of this study was to determine if number of examined lymph nodes (eLN), a proxy for lymphadenectomy, and lymph node ratio (LNR) impact survival.

Methods:

The U.S. National Cancer Data Base (2003-2011) was reviewed for patients with clinical stage I and II resected pancreatic adenocarcinoma.  Patients who received neoadjuvant therapy were excluded.  Patients were stratified by eLN: 0-6, 7-12, 13-15, and >15, and LNR (LNR= #positive nodes/ #eLN):0, 0-0.2, 0.2-0.4, 0.4-0.8, and >0.8.  Univariate and multivariate survival analyses were performed.

 

Results:

14,807 patients with clinical stages I-II resected pancreatic adenocarcinoma were included.  Of these, 15.6% (N=2,309) of patients had 0-6 eLN, 27.1% (N=4,012) had 7-12, 13.4% (N=1,977) had 13-15, and 38.6% (N=5,709) had >15 eLN.  The majority of patients underwent pancreaticoduodenectomy (N=7,720, 55.1%), while the remainder underwent distal pancreatectomy (N=1,833, 13.1%), total pancreatectomy (N=1,850, 13.2%) and other (N=2,604, 18.6%).  Patients who underwent pancreaticoduodenectomy had a median eLN of 11, while those who underwent distal or total pancreatectomy or another procedure had 14. Patients with >15 eLN had significantly improved survival over the other cohorts in both node negative and node positive disease (P<0.001, both).   After controlling for patient, disease, and treatment characteristics, patients with 7-12, 13-15, and >15 eLN had improved survival relative to patients with 0-6 eLN (HR 0.87, p<0.001, HR 0.89, p=0.002, HR 0.82, p<0.001, respectively).

32.6% (N=4,829) of patients had a LNR of 0, 29.8% (N=4,414) £0.2, 9.2% (N=2,843) 0.2-0.4, 11.0% (N=1,643) 0.4-0.8, and 1.9% (N=278) had a LNR >0.8.  Patients with LNR 0 had improved survival in T1-T3 disease (P<0.01).  After controlling for patient, disease and treatment characteristics, higher LNR was negatively associated with survival (LNR 0-0.2: HR 1.44, p<0.001, LNR 0.2-0.4: HR 1.82, p<0.001, LNR 0.4-0.8: 2.03, p<0.001, LNR >0.8, p<0.001).

Even when a suboptimal number of lymph nodes were examined (eLN £6 or £12), higher LNR remained an independent predictor for mortality.

Conclusion:

Greater lymph node retrieval in stage I & II pancreatic adenocarcinoma appears to have therapeutic and prognostic value, even in node-negative disease, suggesting a comprehensive lymphadenectomy is beneficial.  Lymph node ratio is inversely related to survival and may be useful when suboptimal lymph node retrieval is performed.

42.19 Ciclopirox Olamine Causes Growth Inhibition of Esophageal Carcinoma Cells

Posted on January 25, 2017

R. J. Ryan1, P. Ramamoorthy1, S. J. Weir2, S. Anant1, P. DiPasco1  1University Of Kansas,General Surgery,Kansas City, KS, USA 2University Of Kansas,Pharmacology, Toxicology And Therapeutics,Kansas City, KS, USA

Introduction:  

Esophageal carcinoma is a devastating diagnosis with an overwhelmingly poor prognosis. More than 30% of patients have metastatic disease on presentation, and 5 year survival in these patients is 3.5%. Chemo-radiotherapy is the primary treatment modality of advanced disease, but current chemotherapeutic agents only prolong life for months to a few years. Drug repositioning is an important pharmacologic strategy that involves investigation and implementation of known drugs for treatment of new diseases. This method significantly reduces the costs required for establishing the safety of a drug and is associated with higher rates of drug approval. Ciclopirox olamine (CPX) is an antifungal agent that has been on the market since the 1970s. The mechanism of action is believed to include disrupting DNA repair and cell division signals. The compound is also believed to affect the membrane transfer system by interrupting the Na+ K+ ATPase. We have recently been looking at the anti-tumor properties of CPX. In preclinical studies, CPX has been shown to inhibit growth of cell lines for human breast carcinoma, bladder cancer and colon adenocarcinoma. Here, we present our preliminary results of the effects of CPX on esophageal carcinoma cells. 

Methods:  
We maintained two esophageal cancer cell lines, TE-7 and TE-10 in standard culture flasks with RPMI media. Cell lines were exposed to CPX and the effects are reported. Proliferation assays were performed as follows. Cultured cells from each cell line were exposed to CPX for 24, 48 and 72 h, after which cells were lysed and hexosaminidase assay was performed. Colony formation assays were performed as follows. Cultured cells were diluted to 500 cells/mL, plated, and exposed to increasing concentrations of CPX for 48 h. After exposure, cells were incubated in standard media for 10 days. Cells were then fixed and stained with crystal violet dye. Cell cycle analysis was performed on cells from both cells lines after exposure to CPX for 48 h. Cells were permeabilised and treated with propidium iodide before running through flow cytometry. 

Results:
CPX causes growth inhibition of TE-7 and TE-10 esophageal cancer cell lines. Results of proliferation assay revealed growth inhibition of esophageal cancer cells from TE-7 and TE-10 cell lines in a dose and time-dependent manner. Cell cycle assay also showed growth inhibition of both cell lines in a concentration dependent manner. On cell cycle analysis, cells exposed to CPX revealed cell-cycle arrest in G2/M phase

Conclusion:

Ciclopirox olamine (CPX) is an FDA-approved antifungal agent recently shown to have anti-tumor properties. To date, there is no published data on CPX as a potential target of esophageal carcinoma.  We have demonstrated growth inhibition of two esophageal cancer cell lines when exposed to CPX. These data pave the way for further research into the mechanisms of growth inhibition and potential use of this agent in the treatment of esophageal carcinoma.

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