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Background Breast cancer survival is improving due to early detection and treatment advances. However, racial/ethnic differences in tumor biology, stage, and mortality remain. The objective of this study was to analyze presumed disparities at a local level. Methods Breast cancer patients at a county hospital and private hospital from 2010 to 2012 were retrospectively reviewed. Demographic, clinical, pathologic, and surgical data were collected. Comparisons were made between hospital cohorts and between racial/ethnic groups from both hospitals combined. Results 754 patients were included (322 from county hospital and 432 from private hospital). All patients were female. The median age was 54 years at county hospital and 60 years at private hospital ( P < .0001). Racial/ethnic minorities comprised 85% of county hospital patients vs. 12% of private hospital patients ( P < .0001). County hospital patients had a higher grade, clinical/pathologic stage, HER2-positive rate, and mastectomy rate. Compared to other racial/ethnic groups, non-Hispanic white women were more likely to have lower grade and ER-positive tumors. Hispanic/Latina women were younger and were more likely to have HER2-positive tumors. Both Hispanic/Latina and non-Hispanic black women presented at higher clinical stages and were more likely to undergo neoadjuvant chemotherapy and mastectomy. Discussion At county hospital compared to private hospital, the proportion of racial/ethnic minorities was higher, and patients presented at younger ages with more aggressive tumors and more advanced disease. The racial/ethnic disparities that were identified locally are largely consistent with those identified in national database studies. These marked differences at hospitals within a diverse city highlight the need for further research into the disparities.

BACKGROUND: While resection is a recommended treatment for patients with stage 1 hepatocellular carcinoma (HCC), it remains controversial for multifocal disease. We sought to identify patients with multifocal HCC with survival after resection similar to patients with clinical stage 1 HCC. METHODS: The National Cancer Database was queried to identify patients that underwent resection for HCC. RESULTS: In this study, 2990 patients with a single tumor, and 1087 patients with multifocal disease confined to one lobe underwent resection. In the multifocal cohort, patients with clinical stage 3 (HR 1.54, CI 1.31–1.81, p < 0.0001) or 4 (HR 2.27, CI 1.57–3.29, p < 0.0001) disease, and those with moderately-differentiated (HR 1.32, CI 1.06–1.64, p = 0.012) or poorly differentiated/undifferentiated tumors (HR 1.53, CI 1.20–1.95, p = 0.0006) were associated with worse overall survival (OS). There was no difference in OS between patients with well-differentiated clinical stage 2 multifocal HCC and those with all grades of clinical stage 1 HCC (median of 84.8 (CI 66.3–107.2) vs 76.2 months (CI 71.2–81.3), respectively, p = 0.356). CONCLUSIONS: Patients with well-differentiated, clinical stage 2 multifocal HCC confined to one lobe experience similar OS following hepatic resection to patients with clinical stage 1 disease. These findings may impact the management of select patients with multifocal HCC.

Operable gastrointestinal cancers continue to pose significant challenges. Radical resections are rarely curative, and chemotherapy is able to reduce tumor recurrence for only a small percentage of patients. Despite the obvious advantages of extirpation of the identifiable tumor(s), the inflammatory milieu that accompanies surgery and the obligate time off cytotoxic agents allows for activation of remote quiescent disseminated tumor cells, leading to metastatic recurrence. We are conducting a study to determine the safety and efficacy of immediate peri-operative MVT-5873, a cytotoxic monoclonal antibody targeting carbohydrate antigen 19-9 (CA 19-9), in patients undergoing resections pancreatic cancer, cholangiocarcinoma or metastatic colorectal cancer to the liver. Eligible patients will receive a single dose of MVT-5873 three days before resection and four post-operative infusions, before beginning standard adjuvant regimens. MVT-5873 is a human IgG1 antibody isolated from a patient following immunization with a sLe(a)-KLH vaccine. MVT-5873 demonstrated cell surface binding in sLe(a) positive human tumor lines and has been shown to be potent in complement-dependent cytotoxicity assays and antibody-dependent cell mediated cytotoxicity assays. In patients with metastatic CA 19-9 producing pancreatic adenocarcinoma, MVT-5873 treatment has been shown to decrease serum CA 19-9 levels and prevent tumor progression. The use of perioperative MVT-5873 has the potential to reduce recurrence rates and prolong survival after resection. This trial may open the door for investigation of additional and/or synergistic agents in the immediate peri-operative period and usher in a new paradigm in the management of surgically treated cancers. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03801915?term=MVT&rank=3.

BACKGROUND: Adrenocortical carcinoma (ACC) is an aggressive malignancy that frequently metastasizes to the liver. Given the limitations of systemic therapy in this setting, we sought to determine characteristics associated with a two-fold increase in survival with surgical management compared to what has been reported with chemotherapy alone (∼12 months). METHODS: Patients who underwent resection/ablation at our institutions for ACC liver metastases were identified. Those who survived between 12–24 months after metastasectomy were excluded, as the aim was to characterize patients who most clearly benefited from these procedures. Clinicopathologic and treatment characteristics were assessed for associations with survival. RESULTS: Sixty-two patients met inclusion criteria, of whom 44 survived greater than 24 months and 18 survived less than 12 months. Patients with extended survival were less likely to have functioning tumors (p=0.047), had fewer liver metastases (p=0.047), and a longer disease-free interval (DFI) (median 17.6 vs 2.3 months, p

Primary gallbladder neuroendocrine tumors (NETs) are rare, poorly understood cancers infrequently encountered at even the largest of tertiary referral centers. We therefore sought to identify a large cohort of patients with gallbladder NETs using a national database, with the aim of defining treatment modalities employed and survival associated with these uncommon malignancies. Patients with primary gallbladder NETs were identified in the National Cancer Database, and clinicopathologic characteristics were recorded. A univariate log-rank survival analysis was completed for patients who underwent resection. Parameters found to be significant were entered into a multivariate accelerated failure time analysis. For context, survival comparisons were included for patients who underwent resections for NETs at any gastrointestinal site and for gallbladder adenocarcinoma. Overall, 754 patients with gallbladder NETs were identified. Patients were predominantly female (n = 518, 69%), White (n = 503, 67%), presented with stage IV disease (n = 295, 39%) and had high-grade lesions (n = 312, 41%). The majority underwent resection (n = 480, 64%), primarily simple cholecystectomy (n = 431, 90%), whereas a minority received multimodal therapy (n = 145, 21%). Among patients who underwent resection, older age (p = 0.001), large cell histology (p = 0.012), and positive margins (p = 0.030) were independently associated with worse overall survival. Patients with gallbladder NETs had improved survival relative to those with gallbladder adenocarcinoma (p = 0.001), but significantly worse survival than patients with NETs from other gastrointestinal sites (p

INTRODUCTION. Laparoscopic approach to liver resection is feasible and safe, though its utilization with intrahepatic cholangiocarcinoma (ICC) remains poorly documented. We sought to evaluate the use laparoscopy for ICC, and to examine adherence to oncologic standards. METHODS. The National Cancer Database was queried for patients who underwent resection for ICC. Patients were stratified by laparoscopic (LLR) versus open liver resection (OLR). Clinicopathologic parameters and hospital volumes were recorded. RESULTS. In total, 2309 patients with ICC underwent hepatic resection (1997 OLR, 312 LLR) between 2010 and 2015. LLR increased from 12 to 16% during the study period and was utilized more commonly than OLR for wedge and segmental resections (56% vs. 33%, p

Patients with hepatopancreatobiliary (HPB) malignancies undergoing resection are prone to venous thromboembolism (VTE), and current guidelines recommend up to 28 days of chemoprophylaxis after major surgery. We sought to determine the practice patterns among HPB surgeons for use of chemoprophylaxis after discharge. A survey on VTE chemoprophylaxis after oncologic HPB operations was distributed to attending surgeons at the 18 HPB fellowship training programs in the United States and Canada. Of the HPB surgeons surveyed, 44 (44%) responded. VTE prophylaxis is used by 93% of respondants in the inpatient postoperative setting. Chemoprophylaxis after discharge for pancreaticoduodenenctomy and distal pancreatectomy is utilized by 45% and 39% of respondants, respectively. Of those who prescribe chemoprophylaxis after discharge, 79% and 88% prescribe it for the recommended 28 days after pancreaticoduodenectomy and distal pancreatectomy, respectively. Chemoprophylaxis after discharge for major and minor hepatectomy is utilized by 39% and 26% of respondents, respectively. Of those who prescribe chemoprophylaxis after discharge, 67% and 55% provide it for the recommended 28 days after major and minor hepatectomy, respectively. Despite documented prolonged postoperative thrombogenic risk, the use of chemoprophylaxis following discharge after pancreatic and liver resections for cancer was moderate among surveyed HPB surgeons.

An improved understanding of the clinical behavior and molecular biology of melanoma has led to multiple practice-changing advancements in recent decades. Nevertheless, the gold standard for primary melanoma treatment, in most cases, continues to be complete surgical removal of the tumor with a wide excision. Data from multiple prospective randomized trials have led to the development of evidence-based clinical recommendations for melanoma resection margins that are based on a lesion’s Breslow depth. Although resection presents the most effective means of local disease control, some patients are not surgical candidates for a variety of anatomic, cosmetic, or medical reasons. These patients may benefit from non-operative treatment options, which including topical therapies, intralesional injections, radiation therapy, and systemic therapy.

Background Alveolar soft part sarcoma is a rare, histologic subtype of soft tissue sarcoma that remains poorly defined. We aimed to describe patient characteristics and treatment patterns and to examine factors associated with survival for patients with alveolar soft part sarcoma. Methods After identifying patients with alveolar soft part sarcoma in the National Cancer Database, we recorded their clinicopathologic characteristics. Univariable log-rank survival analysis and Cox proportional hazards model were employed. For context, survival comparisons were included for patients with other sarcoma subtypes. Results Overall, 293 patients with alveolar soft part sarcoma were identified. Interestingly, patients with head and neck tumors were least likely to present with distant disease (40%, P = .025). The majority of patients underwent resection (n = 183, 63%). Among those, no predictors of lesser survival were identified other than the presence of metastases (hazard ratio 6.04, P ≤ .001). Patients with stage IV alveolar soft part sarcoma who underwent resections experienced improved survival relative to similar patients with more common subtypes of soft tissue sarcomas (P ≤ .001). Conclusion Alveolar soft part sarcoma is exceedingly rare, and patients often present with metastases. Primary tumors can occur anywhere in the body, and location impacts the rates of metastases at presentation. Resection is associated with a favorable survival advantage when compared to other, more common histologic subtypes of soft tissue sarcomas.

The rate of positive margins after breast conserving surgery (BCS) can be as high as 50 per cent, and optimal techniques for reducing rates of positive margins are presently debated. Our institution has previously demonstrated low rates of margin re-excision using a standardized approach to intraoperative selective margin excision for patients undergoing BCS. We hypothesized that this approach can be used for patients with ductal carcinoma in situ (DCIS) and can yield similar rates when compared with invasive cancer. We performed a retrospective analysis of women with breast cancer who underwent BCS from January 2012 through July 2016 using our institution's standardized approach to selective margin resection. Of the 152 patients who underwent BCS, there were 30 (20%) with DCIS and 122 (80%) with invasive cancer. There was no statistically significant difference in re-excision rates for DCIS (13.3%) and invasive cancer (13.1%). Notably, the DCIS group had a larger mean lesion size ( P = 0.00009); however, the lesion was visible on ultrasound more often in the invasive cancer group ( P = 0.007). This standardized approach to intraoperative selective margin excision can produce similar rates of margin re-excision for DCIS and invasive cancer and may be a viable option for lowering re-excision rates for patients with DCIS.

BACKGROUND/OBJECTIVES Gallbladder squamous cell carcinoma (SCC) is an uncommon malignancy whose rarity has made it particularly challenging to study. We utilized a national database to shed light on the clinicopathologic characteristics, management patterns, and survival associated with these tumors. METHODS Patients with gallbladder SCC were identified in the National Cancer Database. Clinicopathologic and treatment characteristics were recorded and compared with adenocarcinoma for context. Univariate and multivariable survival analyses were completed for patients who underwent resection. RESULTS Overall, 1084 patients with SCC and 23 958 patients with adenocarcinoma were identified. Compared with those with adenocarcinoma, patients with SCC had higher grade tumors (P

The demand for training in complex general surgical oncology (CGSO) fellowships currently exceeds the number of positions offered; however, there are scarce data defining the applicant pool or characteristics associated with successful matriculation. Our study described the applicant population and to determine factors associated with acceptance into the fellowship. Data were extracted from the Electronic Residency Application System for applicants in 2015 and 2016 and stratified based on matriculation status. Applicant demographics, including medical education, residency, and research achievements, were analyzed. Academic productivity was quantified using the number of peer-reviewed publications as well as the journal with the highest impact factor in which an applicant’s work was published. Data were gathered on a total of 283 applicants, of which 105 matriculated. The overall population was primarily male (63.2%), Caucasian (40.6%), educated at a U.S. allopathic medical school (53.4%), and trained at a university-based General Surgery residency (55.5%). Education at a U.S. allopathic school (OR = 5.63, p

Single-site robotic cholecystectomy (SSRC) accounts for most of the robotic surgery cases performed by general surgeons at our institution since acquiring the da Vinci Si Surgical SystemTM (Intuitive Surgical, Inc., Sunnyvale, CA) in 2014. We sought to determine whether a SSRC program is safe to start in a public teaching hospital and to determine whether resident participation in this procedure is feasible. Data on age, gender, race, BMI, total operative time, length of stay, comorbidities, and conversion from laparoscopic to open surgery were examined for elective SSRC and laparoscopic cholecystectomies (LCs) performed by two faculty surgeons between February 2015 and August 2015. Thirty-eight patients underwent elective SSRC, whereas 27 patients underwent LC. Residents participated as operating surgeons for some portion of the case in 15 SSRC cases and in all LC cases. There were no significant differences in operative time, length of stay, or 30-day readmission rates, regardless of resident involvement. Patients in the SSRC group had a significantly lower BMI (25.8 vs 33.7, P = 0.008). This study suggests that resident participation does not increase complications or total operative time and that SSRC is a safe procedure to start in a public teaching hospital after proper faculty and resident training.

BACKGROUND AND OBJECTIVES: Chemotherapeutic options for patients with recurrent/metastatic adrenocortical carcinoma (ACC) are limited, leading to consideration for surgical management. We sought to determine characteristics associated with an unequivocal survival benefit amongst patients undergoing re-resection or metastasectomy. METHODS: Patients who underwent surgery for recurrent/metastatic ACC were identified and stratified into two groups: those with postoperative survival comparable with what has been reported with chemotherapy alone (24 months). Those who survived between 12 and 24 months were excluded, as the objective was to characterize patients who most distinctly benefited from resection. Clinicopathologic and treatment variables were evaluated for associations with survival. RESULTS: Forty-three patients survived more than 24 months and 15 patients died less than 12 months after reoperation. Tumor stage (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.45–0.96) and disease-free interval (DFI; OR, 3.23; 95% CI, 1.68–6.22) were associated with prolonged survival. Tumor size, hormonal status, resection margin, and treatment with chemotherapy, radiation, and mitotane were not associated with prolonged survival. Patients who survived more than 24 months underwent more procedures for subsequent recurrences (median 4 vs 2; P < .001). CONCLUSION: Stage and DFI can help select optimal candidates for resection of recurrent/metastatic ACC. Patients selected for surgical management should be informed of the likelihood of requiring multiple interventions.

Background The optimal approach to biliary drainage for patients with supra-ampullary cholangiocarcinoma remains undetermined. Violation of sphincter of Oddi results in bacterial colonization of bile ducts and may increase postdrainage infectious complications. We sought to determine if rates of cholangitis are affected by the type of drainage procedure. Methods We examined the Surveillance, Epidemiology, and End Results-Medicare linked database from 1991 to 2013 for cholangiocarcinoma. Biliary drainage procedures were categorized as sphincter of Oddi violating (SOV) or sphincter of Oddi preserving (SOP). Patients were stratified by resection. Results A total of 1914 patients were included in the final analysis. A total of 1264 patients did not undergo a postdrainage resection (SOP 83, SOV 1181) while 650 did undergo a postdrainage resection (SOP 26, SOV 624). For those patients not undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was 19% compared with 34% in the SOV cohort (P = 0.007). For those patients undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was less than 42.3% compared with 30% in the SOV cohort (P = 0.66). Conclusion For patients with supra-ampullary cholangiocarcinoma that did not undergo resection, biliary drainage procedures that violated the sphincter of Oddi were associated with increased rates of cholangitis.

BACKGROUND: Clinically lymph node positive (cLNP) intrahepatic cholangiocarcinoma (ICC) carries a poor prognosis, without clear management guidelines for the practicing clinician. We sought to evaluate current practice patterns for cLNP ICC, including associations with survival. METHODS: The National Cancer Database was queried for patients with cLNP ICC, without extrahepatic metastases. RESULTS: We identified 1023 patients with cLNP ICC, 77%% (n = 784) of whom received chemotherapy alone. Resection was undertaken in 23% (n = 239) of patients and was most commonly utilized in combination with chemotherapy (n = 150). Median survival for all patients was 13.6 months. Patients undergoing resection in combination with chemotherapy were associated with an improved survival (22.5 months) as compared to those patients receiving chemotherapy alone (11.9 months) or resection alone (12.4 months) (p < 0.01). Finally, we compared the survival of patients with cLNP ICC with that of patients with pathologically proved lymph node positive (pLNP) ICC, all of whom were treated with resection with chemotherapy, and found no difference in survival (22.5 months–19.3 months, p = 0.99, respectively). CONCLUSIONS: While the decision to pursue resection for ICC is multifactorial and patient specific, the presence of clinically positive LNs should not represent a contraindication.

BACKGROUND. There is significant demand for training in Complex General Surgical Oncology (CGSO) fellowships. Previous work has explored objective quantitative metrics of applicants that matriculated to CGSO fellowships; however, ambiguity remains concerning academic benchmarks and qualitative factors that impact matriculation. STUDY DESIGN. A web-based survey was sent to each ACGME/SSO-approved CGSO fellowship training program. The survey was comprised of 24 questions in various forms, including dichotomous, ranked, and five-point Likert scale questions. RESULTS. Twenty-nine of 30 program directors (97%) submitted complete survey responses, representing 64 of the 65 CGSO fellowship positions (99%) currently offered. Programs received a mean of 73 applications per cycle (range 50–125) and granted a mean of 26 interviews (range 2–45). Seventy-two percent of programs had an established benchmark for ABSITE score percentile before offering a candidate an interview, with 62% of those programs setting that benchmark above the 50(th) percentile. The majority of programs also had established benchmarks for quantity of first author publications (mean: 2.3) and all publications of any authorship (mean: 4.4). An applicant’s interview was ranked as the most important factor in determining inclusion on the program’s rank list. The ability to work as part of a team, interpersonal interaction/communication abilities, and operative skills were rated as most important applicant characteristics, whereas an applicant’s personal statement was ranked as least important. CONCLUSIONS. After established academic benchmarks have been met, a multitude of factors influences ranking of applicants to the CGSO fellowship, most of which are assessed at the interview.

Introduction: Although liver metastasis is the major cause of pancreatic cancer mortality, the mechanisms by which KRAS-driven pancreatic tumor cells initiate metastatic outgrowth in the liver are unknown. High-throughput next-generation sequencing studies have revealed that driver mutations and copy number alterations are highly concordant between matched primary tumors and metastases in pancreatic cancer. This suggests that the mechanisms leading to the metastatic outgrowth and colonization involve the cooperation of many other cellular factors in addition to driver mutations. We hypothesize that in the absence of metastasis-specific driver mutations, the initial adaptation and outgrowth steps of metastasis are driven by metabolic reprogramming, which is induced or activated in vivo under physiologic conditions of the target organ like nutrient deprivation. Method: To identify the metabolic drivers, a retroviral cDNA library was generated from a highly metastatic pancreatic cell line (M-4964Liv) derived from a KPC mouse that forms macroscopic liver lesions upon splenic injection in mice. The cDNA library was then transduced into dormant pancreatic KPC cells (D-4964Liv) cells that do not give liver lesions upon splenic injection in mice. This methodology will allow all the cDNAs from the metastatic cells to express in the dormant cells, but only those cDNAs that can trigger the dormant cells to outgrow will give rise to a metastatic liver lesion. Results: The screening strategy led to the identification of the translational regulator general control of amino-acid synthesis 1-like 1 (GCN1). We show that activation of GCN1 at physiologic glutamine activates the master regulator of metabolic homeostasis ATF4, oncogenic mTORC1 signaling, and pluripotency factor SOX2. Consistent with this, knockdown of GCN1 not only inhibits ATF4, mTORC1, and expression of Sox2 but dramatically abrogates liver metastasis in immunocompetent mice upon intrasplenic injection, suggesting that GCN1-ATF4 signaling is indispensable for metastatic outgrowth. Mechanistic insights reveal that the GCN1-ATF4 signaling pathway is governed by a competitive inhibitor, IMPACT, which is induced at physiologic glutamine and inhibits GCN1 function. Surprisingly, the expression of IMPACT is lost in highly metastatic pancreatic cell lines, leading to activation of the GCN1-ATF4 pathway and mTORC1 at physiologic glutamine, while overexpression of IMPACT effectively inhibits the pathway and reduces metastatic outgrowth of pancreatic cancer cells in the liver in immunocompetent mice. Conclusions: The loss of expression of IMPACT leading to GCN1-dependent activation of ATF4 and mTORC1 at physiologic levels of glutamine provides metabolic plasticity during the initial steps of metastatic outgrowth. Thus, inhibitors targeting the GCN1-ATF4 pathway or mTORC1 will greatly benefit pancreatic adenocarcinoma patients by inhibiting the outgrowth of their metastatic disease. Citation Format: Surajit Sinha, Reed I Ayabe, Alok Ranjan, Michael Wach, Samantha Ruff, Kirsten Remmert, Elke Van Beek, Imani Alexander, James D. McDonald, Shreya Gupta, Eileen Li, Jonathan Hernandez. IMPACT inhibits metastatic outgrowth in pancreatic cancer by restraining GCN1-ATF4 signaling [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A50.

Introduction: Pancreatic cancer remains a challenging disease, with an overall cumulative 5-year survival rate less than 5%. Metastases are responsible for over 90% of cancer-related deaths. Despite significant progress made in cancer drug development, our understanding of the mechanisms driving metastatic outgrowth remains limited. Systematic dissection of the molecular mechanisms underlying metastatic progression is necessary for the development of new therapeutic strategies. Method: To identify the important genes driving metastatic outgrowth, we performed a novel in vivo cDNA screening using a high metastatic-capacity line (M-4964Liv) and a low metastatic-capacity line (D-4964Liv), which we derived from in vivo passaging of a cell line from a KPC mouse. MBD3 regulated MYC stability was examined by cycloheximide chase assay and further confirmed by polymerase chain reaction and Western blotting. Phenotypic effect of MBD3 was evaluated by sphere assay in 3D and intrasplenic model of liver metastasis in vivo. Results: Methyl-CpG binding domain protein 3 (MBD3) was identified in our screen. We initially evaluated MBD3 with pancreatosphere formation assays. In doing so, we showed that MBD3 overexpression leads to significant augmentation of sphere formation, while knockdown abrogates sphere-forming capacity. We subsequently validated MBD3 in vivo with liver metastases assays, through both overexpression and knockdown, as being a facilitator of metastatic outgrowth. In addition, we observed high expression of MBD3 across a panel of pancreatic cancer cell lines that readily form liver metastases upon splenic injection. To understand how MBD3 may lead to metastases, we used a cycloheximide chase assay and determined that MBD3 overexpression increases MYC stability. With knockout of MBD3 using CRISPR/Cas9, we demonstrated that MBD3 mediates MYC stabilization by increasing the expression of phospho-MYC at Ser-62 (stable form of MYC). In the absence of MBD3, we observed an increase in phospho-MYC at Thr-58 expression (unstable form of MYC). Consequently, we observed a decrease in expression of CDK7, a downstream target of MYC, after MBD3 knockdown. CDK7 is a known master regulator of cyclin-dependent kinases, and loss of CDK7 drives cells to quiescence. Intriguingly, downregulation of MYC expression, through destabilization with MBD3 knockdown, led to activation of negative feedback pathway as observed with an increase in phospho-GSK3β at Ser-9, which inactivates GSK3β and thereby decreases MYC ubiquitination. Conclusion: MBD3 leads to stabilization of MYC in pancreatic cancer cell lines, which results in an increase in the ability to form liver metastases. Further dissection of this previously undescribed MBD-mediated mechanism may lead to new therapeutic targeting of MYC for patients with pancreatic cancer. Citation Format: Alok Ranjan, Surajit Sinha, Reed Ayabe, Michael Wach, Samantha Ruff, Shreya Gupta, James McDonald, Kirsten Remmert, Imani Alexander, Jonathan Hernandez. MBD3 stabilizes MYC, leading to metastatic outgrowth of pancreatic cancer in the liver [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C44.

Background Metastatic squamous cell carcinoma (SCC) to the axillary or inguinal lymph nodes from an unknown primary source is rarely encountered. We sought to evaluate a cohort of patients with metastatic SCC managed by lymphadenectomy to determine their survival and to determine which clinicopathologic factors were associated with outcome. Methods All patients undergoing axillary or inguinal lymphadenectomy for SCC at our institution were identified retrospectively. Patients were stratified by unknown primary (UP) vs known skin primary (KP) tumors. Pertinent data on patient, tumor, and treatment variables was collected. Results We identified 51 patients who met inclusion criteria. Of those, 20 patients (39%) had UP metastatic SCC and 31 patients (61%) had KP. The 5-year overall survival for UP was 65%, as compared to 49% for KP (p = 0.16). Cumulative incidence of recurrence was 46%. Cox regression failed to demonstrate a significant association between KP vs UP, HPV status, chemotherapy, or radiation with survival. Conclusions Nearly two-thirds of patients undergoing axillary or inguinal lymphadenectomy for metastatic SCC of unknown primary were alive five years following the procedure.

BACKGROUND: Portal lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is encouraged for staging purposes, though it is under-utilized for clinically early-stage tumors. We sought to determine if any factor knowable prior to resection influences rates of portal lymph node metastases. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program (1973–2014) database was queried to identify patients with T1/T2 ICC undergoing resection. Patients were stratified by lymph node (LN) status. Patients deemed LN negative required examination of six or more LNs (AJCC guidelines). RESULTS: One-hundred and fifty-two patients were included in the analysis (LN negative: 38, LN positive: 114). Patients with LN negative cancers experienced prolonged overall survival as compared to patients with positive LNs (median 77 months vs 19 months, respectively p < 0.001). Twelve patients had well-differentiated tumors (G1), 92 patients had moderately-differentiated tumors (G2) and 58 patients had poorly-differentiated tumors (G3). Tumor grade (OR 3.9, CI 1.1–13.7, p = 0.031) and male sex (OR 2.6, CI 1.1–6.1, p = 0.022) were associated with positive LNs on multivariable logistic regression analysis. CONCLUSION: Intermediate/High grade and male sex are associated with high rates of lymph node metastasis for patients with early-stage ICC, which portends abbreviated overall survival.

Single-site robotic cholecystectomy (SSRC) accounts for most of the robotic surgery cases performed by general surgeons at our institution since acquiring the da Vinci Si Surgical SystemTM (Intuitive Surgical, Inc., Sunnyvale, CA) in 2014. We sought to determine whether a SSRC program is safe to start in a public teaching hospital and to determine whether resident participation in this procedure is feasible. Data on age, gender, race, BMI, total operative time, length of stay, comorbidities, and conversion from laparoscopic to open surgery were examined for elective SSRC and laparoscopic cholecystectomies (LCs) performed by two faculty surgeons between February 2015 and August 2015. Thirty-eight patients underwent elective SSRC, whereas 27 patients underwent LC. Residents participated as operating surgeons for some portion of the case in 15 SSRC cases and in all LC cases. There were no significant differences in operative time, length of stay, or 30-day readmission rates, regardless of resident involvement. Patients in the SSRC group had a significantly lower BMI (25.8 vs 33.7, P = 0.008). This study suggests that resident participation does not increase complications or total operative time and that SSRC is a safe procedure to start in a public teaching hospital after proper faculty and resident training.

BACKGROUND. Primary gallbladder neuroendocrine tumors (NETs) are rare, poorly understood cancers infrequently encountered at even the largest of tertiary referral centers. We therefore sought to identify a large cohort of patients with gallbladder NETs using a national database, with the aim of defining treatment modalities employed and survival associated with these uncommon malignancies. METHODS. Patients with primary gallbladder NETs were identified in the National Cancer Database, and clinicopathologic characteristics were recorded. A univariate log-rank survival analysis was completed for patients who underwent resection. Parameters found to be significant were entered into a multivariate accelerated failure time analysis. For context, survival comparisons were included for patients who underwent resections for NETs at any gastrointestinal site and for gallbladder adenocarcinoma. RESULTS. Overall, 754 patients with gallbladder NETs were identified. Patients were predominantly female (n = 518, 69%), White (n = 503, 67%), presented with stage IV disease (n = 295, 39%) and had high-grade lesions (n = 312, 41%). The majority underwent resection (n = 480, 64%), primarily simple cholecystectomy (n = 431, 90%), whereas a minority received multimodal therapy (n = 145, 21%). Among patients who underwent resection, older age (p = 0.001), large cell histology (p = 0.012), and positive margins (p = 0.030) were independently associated with worse overall survival. Patients with gallbladder NETs had improved survival relative to those with gallbladder adenocarcinoma (p = 0.001), but significantly worse survival than patients with NETs from other gastrointestinal sites (p

Background The urgency of laparoscopic cholecystectomy for acute cholecystitis is under debate. We hypothesized that nighttime cholecystectomy is associated with decreased length of stay. Methods Retrospective review of 1,140 patients at 2 large urban referral centers with acute cholecystitis who underwent daytime (7 am to 7 pm) versus nighttime (7 pm to 7 am) cholecystectomy was conducted. Results Nighttime cholecystectomy did not affect the overall length of stay (3.7 vs 3.8 days, P = .08) or complication rate (5% vs 7%, P = .5) versus daytime cholecystectomy. Nighttime cholecystectomy was associated with a higher conversion rate to open cholecystectomy (11% vs 6%, P = .008). On multivariable analysis, independent predictors of conversion to open surgery were nighttime cholecystectomy, age, and gangrenous cholecystitis (P = .01). The only predictor of complications was gangrenous cholecystitis (P = .02). Conclusions Nighttime cholecystectomy is associated with an increased conversion to open surgery without decrease in length of stay or complications. These findings suggest that laparoscopic cholecystectomy for acute cholecystitis should be delayed until normal working hours.

Background It has become increasingly important to expose surgical residents to robotic surgery as its applications continue to expand. Single-site robotic cholecystectomy (SSRC) is an excellent introductory case to robotics. Resident involvement in SSRC is known to be feasible. Here, we sought to determine whether it is safe to introduce SSRC to junior residents. Materials and methods A total of 98 SSRC cases were performed by general surgery residents between August 2015 and August 2016. Cases were divided into groups based on resident level: second- and third-years (juniors) versus fourth- and fifth-years (seniors). Patient age, gender, race, body mass index, and comorbidities were recorded. The number of prior laparoscopic cholecystectomies completed by participating residents was noted. Outcomes including operative time, console time, rate of conversion to open cholecystectomy, and complication rate were compared between groups. Results Juniors performed 54 SSRC cases, whereas seniors performed 44. There were no significant differences in patient age, gender, race, body mass index, or comorbidities between the two groups. Juniors had less experience with laparoscopic cholecystectomy. There was no significant difference in mean operative time (92.7 min versus 98.0 min, P = 0.254), console time (48.7 min versus 50.8 min, P = 0.639), or complication rate (3.7% versus 2.3%, P = 0.68) between juniors and seniors. Conclusions SSRC is an excellent way to introduce general surgery residents to robotics. This study shows that with attending supervision, SSRC is feasible and safe for both junior and senior residents with very low complication rates and no adverse effect on operative time.

PURPOSE Steroids are often used as medical therapy for active thyroid eye disease (TED). While high-dose steroids have been shown to be effective in reducing the severity of TED symptoms, the side effects of steroids can be severe. As the pathogenesis of TED is thought to involve the upregulation of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), it has been postulated that anti-TNF agents may be used as steroid-sparing agents in the treatment of TED. This retrospective study was conducted to examine the efficacy of adalimumab, a subcutaneously administered TNF-α antagonist, in treating the inflammatory symptoms of active TED. METHODS All patients in the inflammatory phase of TED who were treated with adalimumab at the Jules Stein Eye Institute over a 2-year period were reviewed. Data concerning visual acuity, optic nerve function, extraocular motility restriction, binocular visual fields, and proptosis were extracted from patient charts. Clinical photographs from baseline and 3-month follow-up visits were reviewed by masked orbital specialists. Each photograph was graded on the severity of conjunctival injection, chemosis, eyelid erythema, and eyelid edema on a scale from 1 to 4. An inflammatory score was calculated as the sum of these 4 elements. Groups were compared using paired t tests. RESULTS Six of 10 patients showed a decrease in inflammatory score while on adalimumab, whereas 3 showed an increase and 1 stayed the same. One patient experienced a significant complication (hospital admission for sepsis). Eight patients received concomitant tapering steroids during the first 6 weeks of therapy as the adalimumab reached maximum efficacy. When data from all 10 subjects were analyzed together, there was no significant change in inflammatory index after 3 months of treatment with adalimumab. However, when the 5 patients with a high baseline inflammatory index (>4) were considered separately, there was a significant improvement (mean decrease of 5.2±2.7; p

PURPOSE To report the association of X-linked ichthyosis and pre-Descemet corneal dystrophy with a deletion of the steroid sulfatase gene (STS) detected with microarray-based comparative genomic hybridization (aCGH). METHODS A slit-lamp biomicroscopic examination and cutaneous examination were performed, after which a saliva sample was collected as a source of genomic DNA. Polymerase chain reaction amplification of each of the 10 exons of STS was performed, as was aCGH on genomic DNA to detect copy number variation. RESULTS The slit-lamp examination revealed punctate opacities in the posterior corneal stroma of each eye. The cutaneous examination demonstrated scaling and flaking skin of the arms and legs. Polymerase chain reaction amplification using primers designed to amplify each of the 10 exons of STS failed to produce any amplicons. Subsequently, aCGH performed on genomic DNA revealed a microdeletion in the Xp22.31 cytoband of approximately 1.7 megabases, containing STS. CONCLUSIONS The identification of a microdeletion within Xp22.3 containing STS with aCGH in an individual with suspected pre-Descemet corneal dystrophy and X-linked ichthyosis demonstrates the clinical utility of copy number variation analysis in confirming a presumptive clinical diagnosis.

TPS4655 Background: Operable hepatopancreatobiliary (HPB) cancers continue to pose significant challenges. Radical resections are rarely curative, and chemotherapy is able to reduce tumor recurrence for only a fraction of patients. Despite the obvious advantages of extirpation of the identifiable tumor(s), the inflammatory milieu that accompanies surgery and the obligate time off cytotoxic agents allows for activation of remote quiescent disseminated tumor cells, leading to metastatic recurrence. We are conducting a study to determine the safety and efficacy of immediate peri-operative MVT-5873, a cytotoxic monoclonal antibody targeting Carbohydrate Antigen 19-9 (CA 19-9), in patients undergoing resections pancreatic cancer, cholangiocarcinoma or metastatic colorectal cancer to the liver. MVT-5873 is a human IgG1 antibody isolated from a patient following immunization with a sLea-KLH vaccine. MVT-5873 has demonstrated cell surface binding in sLea positive human tumor lines and has been shown to be potent in complement-dependent cytotoxicity assays and antibody-dependent cell mediated cytotoxicity assays. In patients with CA 19-9-producing cancers, MVT-5873 treatment has been shown to decrease serum CA 19-9 levels and prevent tumor progression. This trial may open the door for investigation of additional and/or synergistic agents in the immediate peri-operative period and usher in a new paradigm in the management of surgically treated cancers. Methods: This is a prospective, Phase II trial designed to determine the efficacy (increase in 1-yr DFS) and safety of peri-operative MVT-5873 for subjects with operable pancreatic, liver and bile duct cancers with elevated CA 19-9 levels. Patients may receive any standard neoadjuvant regimen prior to enrollment at the NIH Clinical Center in Bethesda, Maryland. Eligible patients will receive a pre-operative dose of MVT-5873 three days prior to the planned operation to remove all demonstrable disease. Following the operation, patients will receive a total of four doses of MVT-5873; the first two doses on postoperative days four and ten. The third dose will be administered on the normally scheduled postoperative clinic visit, followed by a final dose one month after discharge from the hospital and prior to the start of adjuvant treatment. Clinical trial information: NCT03801915 .