4112 Background: Appendiceal cancers are rare tumors with prognostic heterogeneity and treatment-responses dependent upon histologic characteristics. In the 7th edition AJCC manual, mucinous tumors were separated from non-mucinous. Histologic grade was used to distinguish stage IVa from IVb in mucinous tumors. We examined SEER data to investigate the impact of cancer grade on all stages of appendiceal cancer. Methods: We identified patients (pts) with primary appendiceal cancer from the SEER data. Disease-specific survival (DSS) was analyzed based on histologic subtype, stage, and grade. Hazards ratios were calculated using Cox models. Tumor grades were grouped according to AJCC criteria (Grade 1 vs. Grade 2 and above). Results: From 1988-2011 a total of 4491 appendiceal adenocarcinomas were identified in the SEER database; 2026 (45%) pts had mucinous histology and 1578 (35%) had non-mucinous histology. Tumor grade had no impact on DSS in stage I and II tumors. However, in Stage III and IV mucinous tumors higher tumor grade was significantly correlated with worse survival. In pts with Stage III mucinous disease, those with grade 1 tumors had significantly longer DSS than those with tumors ≥ grade 2, with 5-year survival of 75% vs. 44%, respectively (p = 0.02, HR 3.15, 95% CI 1.11 - 8.96). Survival for mucinous stage III grade 1 tumors was similar to stage II tumors. Conclusions: Tumor grade is a strong prognostic indicator in pts with stage III mucinous appendiceal carcinoma. We propose that tumor grade should be included in AJCC staging for stage III mucinous appendiceal cancers, and should not be limited to Stage IV disease as in the AJCC 7th staging manual. Continued investigation into the clinical implications of the observed difference in survival in patients with Stage III appendiceal mucinous adenocarcinoma is warranted, and may potentially alter adjuvant treatment recommendations in selected pts.

Genetic testing is important for comprehensive cancer care. Commercial analysis of the BRCA1/2 genes has been available since 1996, and testing for hereditary breast and ovarian cancer syndrome is well established. The National Comprehensive Cancer Network (NCCN) guidelines identify individuals for whom BRCA1/2 analysis is appropriate and define management recommendations for mutation carriers. Despite recommendations, not all who meet NCCN criteria undergo genetic testing. We assess the frequency that individuals meeting NCCN criteria decline BRCA1/2 analysis, as well as factors that affect the decision-making process. A retrospective chart review was performed from September 2013 through August 2014 of individuals who received genetic counseling at the Levine Cancer Institute. A total of 1082 individuals identified through the retrospective chart review met NCCN criteria for BRCA1/2 analysis. Of these, 267 (24.7%) did not pursue genetic testing. Of the Nontested cohort, 59 (22.1%) were disinterested in testing and 108 (40.4%) were advised to gather additional genetic or medical information about their relatives before testing. The remaining 100 (37.5%) individuals were insured and desired to undergo genetic testing but were prohibited by the expense. Eighty five of these 100 patients were responsible for the total cost of the test, whereas the remaining 15 faced a prohibitive copay expense. Financial concerns are a major deterrent to the pursuit of BRCA1/2 analysis among those who meet NCNN criteria, especially in patients diagnosed with breast or ovarian cancer. These findings highlight the need to address financial concerns for genetic testing in this high-risk population.

Abstract Suppressor cells of myeloid origin contribute to the immune imbalance observed in advanced melanoma. Toll-Like Receptor (TLR) signaling regulates myeloid differentiation and maturation. This study sought to determine the distribution of myeloid suppressor cell subsets in B16F10 melanoma-bearing mice, and modulate their immunosuppressive phenotype by employing a regimen of intracellular TLR agonist(s). Tolerogenic dendritic cells (tDC) and granulocytic myeloid-derived suppressor cells (gMDSC) are primarily observed in the periphery (spleen, PBMC, draining lymph node) of B16F10-bearing mice whereas M2 macrophages (M2) are noted to be intratumoral. Toll-Like Receptor-expression analysis by quantitative PCR showed TLR9 was ubiquitously expressed on tDC, gMDSC and M2, while TLR3 was restricted to tDC and M2. Myeloid conditioning regimens employing TLR3 and 9 agonists were tested in vitro on bone marrow-derived tDC (CD11c+, MHCII+, IL-10+) and M2 (F4/80+, CD206+, Arg1+). Combinations of TLR3+9 agonists or Type A+B TLR9 agonists decreased IL-10/Arg1 mRNA expression while triggered IL-12 expression. In vivo, subcutaneous injection of type A+B TLR9 agonists reduced circulating tDC and gMDSC prevalence by 67% and 82% respectively, intratumoral M2 dropped by 35%. In conclusion, we demonstrate combining type A+B TLR9 agonists promoted immune potency by reducing prevalence of peripheral tDC and gMDSC, as well as tumoral M2 in vivo, and triggering IL-12 production by tDC and M2 in vitro.

Hill, Joshua S. MD; Carpenter, Kendall W. CCRP; Ariyo, Oluwatosin MPH; Han, Yimei MS; Riggs, Stephen B. MD; Salo, Jonathan C. MD, FACS Author Information

Objectives: To evaluate the institutional effect on the outcomes following pancreaticoduodenectomy (PD) for peri-ampullary adenocarcinoma (PACa) performed by the same group of hepatobiliary/pancreatic surgeons in an academic county versus academic private setting.Design: Retrospective review.Setting: Academic county hospital (CH) versus academic private hospital (PH).Patients: All patients undergoing PD from 1/1/2010 to 4/30/2012 for periampullary adenocarcinoma.Main Outcome Measures: Time to intervention, disease stage, completeness of resection, post-operative length of stay, complication rates, and overall survival.Results: Ninety-one patients underwent PD for PACa during the study period: 30 patients at the CH and 59 patients at the PH.No CH patients had private health insurance while only 5% of PH patients had state insurance.CH patients were significantly younger (57.3 versus 67.4 years old, p<0.01) and more frequently Hispanic (66.7% versus 21.3%, p<0.01) compared to PH patients.The mean time from surgical consultation to PD was longer for CH patients than for PH patients but did not achieve significance (35.5 days versus 22.6 days, p=0.09).PH patients had more advanced disease, defined as AJCC Stage IIb, III, or IV, compared to CH patients (73.8% versus 50.0%, p=0.02).Portal venous resection was performed in 26.2% of PH patients while no CH patients underwent portal venous or arterial resection/reconstruction.Though not achieving statistical significance, and R1 or M1 resection was more frequently performed at the PH compared to the CH (23% versus 6.7%, p=0.06).The mean tumor diameter, number of lymph nodes obtained, number of positive lymph nodes, and incidence of perineural or perivascular invasion did not differ between the two groups.No post-operative mortality was observed within 30 days of surgery.Independent predictors of mortality included presence of positive lymph nodes (adjusted OR 1.22 (1.02, 1.46), p=0.034) and increasing tumor size (adjusted OR 1.57 (1.07, 2.46), p=0.049).Interestingly, after adjusting for differences between the groups, the odds of dying for patients admitted to County Hospital were 4.21 times higher, and trended towards significance (adjusted OR 4.21 (1.00, 17.79), p=0.051).Conclusions: The type of institution influences practice patterns in the management of peri-ampullary cancers.Private hospital patients have more advanced disease and undergo significantly more complicated resections with a higher incidence of residual disease compared to county hospital patients.Factors leading to differences in surgical practice pattern must be better understood to ensure optimal treatment for both well insured and poorly insured patient populations.

56 Background: As imaging modalities have improved, breast cancers are increasingly detected at earlier stages. Patients rarely present with axillary disease but no mammographically evident breast tumor. Based on analysis of Surveillance, Epidemiology and End Results (SEER) data, we determined that there has been an increase in incidence of T1aN1 breast cancers. In response, we hypothesize that T0N1 breast cancer incidence has decreased with increased MRI use. Moreover, SEER analysis showed that T1aN1 patients have worse survival than T1bN1 patients. We thus hypothesize that T0N1 patients have worse survival than T1N1 patients. Methods: We identified 36,093 female patients diagnosed with T0-1 N1 invasive breast cancer from the SEER database. We compared patient and tumor characteristics: age, race, histology, hormone receptor status, and diagnosis year group (1990-1994, 1995-1999, 2000-2005, 2006-2010) – by TN category (T0N1/T1aN1/T1bN1/T1cN1) using chi-square test and ANOVA. Kaplan-Meier method was used to estimate disease specific survival (DSS) for each TN category and diagnosis year group separately. Adjusted hazard ratios were estimated using Cox proportional hazards models. Results: Stage distribution was: T0N1=129, T1aN1=1294, T1bN1=6731, and T1cN1=27942 patients. Median ages were 59.6, 56.3, 59.1, and 58.1, respectively. Time trend analysis of T0N1 cancers showed an increase in incidence from 1990 to 1999 and stability after 2000. Five-year DSS was significantly worse for patients with T0N1 tumors than T1aN1 tumors (84.5% versus 94.1%, HR 0.513, p < 0.0001). T0N1 tumors were more likely to be ER negative than T1b-cN1 tumors (23% versus 16%, p < 0.0001). T0N1 tumors were also more likely to be ER negative than T1aN1 tumors, but did not reach statistical significance (23% vs. 20%, p = 0.09). The proportion of lobular cancers was significantly higher in T0N1 than T1aN1 or T1b-cN1 patients (18% versus 8%, p < 0.0001). Conclusions: Our analysis suggests that T0N1 tumors may differ biologically from T1N1 tumors. Although the incidence of T0N1 tumors did not decrease, it remained stable after 2000 when the use of MRI for occult breast cancers became widely accepted. Our second hypothesis that survival is worse in patients with T0N1 tumors was confirmed by our analysis.

44 Background: Screening patients at high-risk for the development of breast cancer consists of MRI and mammography. This retrospective review of screening MRIs in patients designated as high-risk for the development of breast cancer--based on family history alone or a calculated lifetime risk of ≥ 20%--seeks to determine the utility of MRI screening in the detection of early-stage breast cancer. The primary outcome evaluated was stage of malignancy detected through screening imaging. Methods: Results of screening imaging performed between 1/1/08 and 12/31/11 were retrospectively reviewed. Patients who had a personal history of breast cancer were excluded. Remaining screens were categorized based on the following criteria: family history, BRCA mutation or high-risk as calculated by risk assessment tools. Screens with corresponding core biopsies were evaluated for the following: previous imaging obtained, core biopsy pathology and pathologic staging. Results: 118 patients met inclusion criteria and had a subsequent biopsy as a result of screening. Resultant pathology was 75 (64%; 75/118) benign lesions, 19 (16%; 19/118) atypical lesions, and 24 (20%; 24/118) malignant lesions. Of the 24 malignant lesions, 1 (4%; 1/24) were found to be node-positive at the time of surgical staging, and, 23 (96%; 23/24) were node-negative. Conclusions: Four percent (1/24) of patients undergoing high-risk screening had nodal disease at surgical staging, which compares favorably to historical rates of approximately 30% node-positive disease at diagnosis (Krag DN et al., NSABP B-32). Therefore, this study shows that screening high-risk patients can decrease the nodal-positivity rate.