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Background Lymph node (LN) metastasis is associated with decreased survival following resection for pancreatic ductal adenocarcinoma (PDAC). In N0 disease, increasing total evaluated LN (ELN) correlates with improved outcomes suggesting patients may be understaged when LNs are undersampled. We aim to assess the optimal number of examined lymph nodes (ELN) following pancreatectomy. Methods Data from 1837 patients undergoing surgery were prospectively collected. The binomial probability law was utilized to analyze the minimum number of examined LNs (minELN) and accurately characterize each histopathologic stage. LN ratio (LNR) was compared to American Joint Committee on Cancer (AJCC) guidelines. Results As ELN total increased, the likelihood of finding node positive disease increased. An evaluation based upon the binomial probability law suggested an optimal minELN of 12 for accurate AJCC N staging. As the number of ELNs increased, the discriminatory capacity of alternative strategies to characterize LN disease exceeded that offered by AJCC N stage. Conclusion This is the first study dedicated to optimizing histopathologic staging in PDAC using models of minELN informed by the binomial probability law. This study highlights two separate cutoffs for ELNs depending upon prognostic goal and validates that 12 LNs are adequate to determine AJCC N stage for the majority of patients.

Pancreatic cancer ranks one of the worst in overall survival outcome with a 5 year survival rate being less than 10%. Pancreatic cancer faces unique challenges in its diagnosis and treatment, such as the lack of clinically validated biomarkers and the immensely immunosuppressive tumor microenvironment. Recently, the LY6 gene family has received increasing attention for its multi-faceted roles in cancer development, stem cell maintenance, immunomodulation, and association with more aggressive and hard-to-treat cancers. A detailed study of mRNA expression of LY6 gene family and its association with overall survival (OS) outcome in pancreatic cancers is lacking. We used publicly available clinical datasets to analyze the mRNA expression of a set of LY6 genes and its effect on OS outcome in the context of the tumor microenvironment and immunomodulation. We used web-based tools Kaplan-Meier Plotter, cBioPortal, Oncomine and R-programming to analyze copy number alterations, mRNA expression and its association with OS outcome in pancreatic cancer. These analyses demonstrated that high expression of LY6 genes is associated with OS and disease free survival (DFS) outcome. High expression of LY6 genes and their association with OS outcome is dependent on the composition of tumor microenvironment. Considering that LY6 proteins are anchored to the outer cell membrane or secreted, making them readily accessible, these findings highlight the potential of LY6 family members in the future of pancreatic cancer diagnosis and treatment.

Low-grade appendiceal mucinous neoplasms (LAMN) are commonly managed by community surgeons at diagnosis. There is variability in the treatment of LAMN, both by community and specialist providers. We assessed current management practices for LAMN across surgeons with expertise in peritoneal surface malignancies (PSM). An online survey was sent to 106 international surgeons specializing in PSM. The survey assessed demographics, favored pre-referral management, and definitive management practices for LAMN. The response rate was 40% (67% USA, 33% international). Respondents had performed a median of 18 (interquartile range [IQR] 7.75–29) HIPEC cases in the last year, of which 10 (IQR 4–20) were for LAMN. Ninety-three percent reported more than half of LAMN referrals had already undergone surgery—an estimated 50% appendectomy and 20% right hemicolectomy (RH). No surgeon respondents supported performing right hemicolectomy before referral. For LAMN confined to the appendix, 86% of respondents would definitively treat with appendectomy. In the presence of mucinous implants, 24% would observe after appendectomy and 76% would proceed with HIPEC. All would perform HIPEC if implants contained tumor cells. When LAMN involved the appendiceal base, 67% of respondents would proceed with partial cecectomy, while 33% favored RH. Pre-referral management of LAMN is not standardized and 20% of patients were referred to a surgeon who performs CRS/HIPEC after a right hemicolectomy that would not have been recommended. Management of LAMN by surgeons who treat PSM is also variable. Long-term data and identification of prognostic features are necessary to generate consensus on the optimal management of these complex patients.

// Michele M. Gage 1 , Neeraja Nagarajan 1 , Jessica M. Ruck 1 , Joseph K. Canner 1 , Salma Khan 2 , Katherine Giuliano 1 , Faiz Gani 1 , Christopher Wolfgang 1 , Fabian M. Johnston 1 , and Nita Ahuja 1, 3 1 Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA 2 Rehman Medical Institute, Hayatabad, Pakistan 3 Department of Surgery, Yale University, New Haven, Connecticut, USA Correspondence to: Nita Ahuja, email: nita.ahuja@yale.edu Keywords: sarcoma; mesenchymal tumors; connective tissue tumors; SEER; trends of sarcoma Received: November 06, 2018 Accepted: February 19, 2019 Published: March 29, 2019 ABSTRACT Background and objectives: Sarcomas represent a heterogeneous group of tumors, and there is lack of data describing contemporary changes in patterns of care. We evaluated the epidemiology of sarcomas over 12 recent years Methods: The Surveillance, Epidemiology and End Results (SEER) database was queried for sarcoma cases from 2002-2014. Patient, tumor and treatment factors, and trends over time were studied overall and by subtype. Univariable and multivariable logistic regression models and 5-year survival and cause-specific mortality (CSM) were summarized. Results: There were 78,527 cases of sarcomas with an overall incidence of 7.1 cases per 100,000 people, increasing from 6.8 in 2002 to 7.7 in 2014. Sarcoma NOS(14.8%) and soft tissue(43.4%) were the most common histology and primary site, respectively. A majority of tumors were high-grade(33.6%) and >5 cm(51.3%). CSM was 28.6% and 5-year survival was 71.4%. Many patients had unknown-grade(42.2%), which associated with 2.6 times increased odds of no surgical intervention. Conclusions: This comprehensive national study highlights important trends including increasing incidence, changing histologic types, and underestimation of true incidence. A large proportion of sarcomas are inadequately staged (unknown-grade 42.2%) with lack of appropriate surgical treatment. Our study highlights need for standardization of care for sarcomas.

Low-grade appendiceal mucinous neoplasms (LAMN) are commonly managed by community surgeons at diagnosis. There is variability in the treatment of LAMN, both by community and specialist providers. We assessed current management practices for LAMN across surgeons with expertise in peritoneal surface malignancies (PSM).An online survey was sent to 106 international surgeons specializing in PSM. The survey assessed demographics, favored pre-referral management, and definitive management practices for LAMN.The response rate was 40% (67% USA, 33% international). Respondents had performed a median of 18 (interquartile range [IQR] 7.75-29) HIPEC cases in the last year, of which 10 (IQR 4-20) were for LAMN. Ninety-three percent reported more than half of LAMN referrals had already undergone surgery-an estimated 50% appendectomy and 20% right hemicolectomy (RH). No surgeon respondents supported performing right hemicolectomy before referral. For LAMN confined to the appendix, 86% of respondents would definitively treat with appendectomy. In the presence of mucinous implants, 24% would observe after appendectomy and 76% would proceed with HIPEC. All would perform HIPEC if implants contained tumor cells. When LAMN involved the appendiceal base, 67% of respondents would proceed with partial cecectomy, while 33% favored RH.Pre-referral management of LAMN is not standardized and 20% of patients were referred to a surgeon who performs CRS/HIPEC after a right hemicolectomy that would not have been recommended. Management of LAMN by surgeons who treat PSM is also variable. Long-term data and identification of prognostic features are necessary to generate consensus on the optimal management of these complex patients.

Radical antegrade modular pancreatosplenectomy (RAMPS) has been adopted by some surgeons in the treatment of left-sided pancreatic cancer (PDAC). Low disease incidence and heterogenous disease biology make robust prospective comparison of RAMPS and standard distal pancreatosplenectomy (DPS) difficult.Consecutive cases of chemo-naïve patients undergoing open RAMPS and DPS for PDAC between 2010-2017 at two international high-volume pancreatectomy centers were compared. Cox proportional hazard modeling was utilized for multivariate analysis.We identified 193 DPS and 253 RAMPS during the study period. DPS was associated with higher rates of median estimated blood loss (500 vs. 300 cc, P0.001), median total harvested lymph nodes (18 vs. 12, P0.001) and R0 resection (94.3% vs. 88.9%, P=0.013). There were no differences in rates of postoperative pancreatic fistula (16.5% vs. 17.8%, P=1) or postoperative hemorrhage (5.9% vs. 3.6%, P=0.385) (DPS vs. RAMPS). After controlling for significant clinical pathological parameters, RAMPS was associated with non-superior recurrence-free survival (RFS) (HR 0.29; 95% CI, 0.07-1.27, P=0.101) and overall-survival (HR 1.03; 95% CI, 0.71-1.49, P=0.895) compared with DPS. Similar results were observed in node-positive patients.RAMPS is safe and effective in the treatment of PDAC, but is not associated with an improvement in either RFS or overall-survival over DPS.

Introduction: The 21-gene recurrence score (RS) assay categorizes hormone receptor positive, node negative breast cancers (BC) into 3 risk groups for recurrence. We previously showed that the AAMC Model, using only standard pathology data, accurately does the same. This study compares the recurrence rate of the AAMC Model's risk groups to RS-based risk groups. A 2-step approach then is used, in which the AAMC model is applied first, and the RS assay is used only for AAMC intermediate risk cases. AAMC intermediate cases were reclassified by RS into low or high risk groups. Methods: From a prospective registry of newly diagnosed BC, we selected invasive, hormone receptor positive, HER2 negative, lymph node negative cases from 2005 to 2015 tested with RS assay. Five-year Kaplan-Meier distant recurrence rates were calculated for each risk category. Results: 1268 cases were included. Five-year recurrence rates were similar between the AAMC Model's low risk group and RS30 high risk group. Applying the RS assay to the 715 cases in the AAMC Model's intermediate group resulted in re-classifying 417 (58%) as low risk and 41 (6%) as high risk. Using RS alone, 33% of cases were intermediate risk (n=424), whereas in the 2-step approach 20% were intermediate risk (n=257). For the 2-step approach, the 5-year distant recurrence rate was 3.3% for the low risk group (n=740) and 24.4% for the high risk group (n=271). Conclusions: Five-year recurrence rates in the AAMC Model's low and high risk groups were similar to those in RS-based risk groups. The 2-step approach, with RS used only for AAMC intermediate cases, resulted in larger low and high risk groups with equivalent prognostic accuracy, compared to use of the RS assay alone. The 2-step approach reliably identifies a large number of patients unlikely to benefit from 21 gene assay and provides substantial cost savings. Kaplan-Meier Calculated 5-year Distant Recurrences Rates for 4 Models: 1268 Patients Oncotype DXTAILORxAAMC Model2 Step Model with OncotypeDX for AAMC IntermediatesLow RiskRS < 18 (n=703)RS < 11 (n=250)Grade 1 and PR ≥ 1% (n=323)AAMC Low or AAMC intermediate/RS 30 (n=141)RS > 25 (n=231)Grade 3 or ER < 20% (n=230)AAMC High or AAMC intermediate/RS > 30 (n=271) 23.0% (95% CI 14.7 – 31.3%, nf=27)22.9% (95% CI 15.9 – 29.9%, nf=39)22.8% (95% CI 16.1 – 29.5%, nf=41)24.4% (95% CI 18.0 – 30.7%, nf=51)RS= Recurrence Score, nf=number of recurrences, CI = confidence interval. Citation Format: Mylander C, Rosman M, Gage M, Fujii T, Le Du F, Raghavendra A, Sinha A, Espinosa Fernandez JR, James A, Ueno N, Tafra L, Jackson R. Getting the most out of the 21-gene recurrence score assay: Increasing actionable results with a combined pathologic-genomic model [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-09-05.

Up to 50% of patients with stage II or III colon cancer are estimated to develop locoregional recurrence, distant metastasis, or metachronous colon cancers within 5 years of initial treatment. Given the high risk of recurrence, surveillance is critical, but what is the optimal frequency and testing of surveillance, and is it possible to tailor surveillance plans based on risk prediction tools? We reviewed the current national guidelines from 6 reputable oncologic organizations, as well as 10 randomized controlled trials and numerous meta-analyses in the last 22 years evaluating more intensive to less intensive surveillance to answer this question. Currently available adjunct testing, such as genomic testing, and risk calculators were also evaluated. Overall, high-frequency surveillance, to a limit, has been established as superior to less frequency surveillance. Future research will likely demonstrate evidence for adjunct testing for personalized surveillance screening based on individual recurrence risk.

Since the introduction of laparoscopy as an adjunct to abdominal surgery in the 1980’s, surgeons have sought to compare the clinical outcomes of minimally invasive procedures with their parent operations.

Hilar cholangiocarcinomas (HCs) are a diverse group of aggressive tumors often diagnosed late in disease due to their typically longitudinal spread along the biliary system. Only approximately one-third of HCs are the candidates for resection, which offers the only chance for cure. However, even following resection, recurrence is common, and 5-year survival rates after surgery remain dismal at 20 to 42%. A thorough preoperative work-up and risk stratification for major surgery are critical to treatment success and maximizing the likelihood of an R0 resection. Due to the relatively few large phase III randomized controlled trials for HC, data are lacking on the optimal adjuvant treatment. Recent results of the BILCAP trial are promising for improved survival after surgery with adjuvant therapy, particularly capecitabine. When resection is not an option, prognosis is poor with median survival of less than 12 months. However, there are multiple chemotherapy-based treatment options that have demonstrated prolonging survival, with combined gemcitabine and cisplatin as first-line therapy. Liver transplantation should be considered on protocol for unresectable HC in the absence of metastatic disease. Palliative options, such as photodynamic therapy or radiation, may also be considered in advanced disease. This review contains 2 figures, 5 tables, and 41 references. Key Words: adjuvant therapy in cholangiocarcinoma, hilar cholangiocarcinoma, Klatskin tumor, metastatic cholangiocarcinoma, perihilar cholangiocarcinoma, portal dissection, surgery for hilar cholangiocarcinoma, outcomes in hilar cholangiocarcinoma

Background: Liver resection in patients with neuroendocrine liver metastasis (NELM) provides a survival benefit, yet the optimal extent of resection remains unknown. We sought to examine outcomes of patients undergoing non-anatomic (NAR) versus anatomic liver resection (AR) for NELM using a large international cohort of patients. Methods: Two hundred and fifty-eight patients who underwent curative intent liver resection from January 1990 to December 2016 were identified from eight institutions. Patients were excluded if they underwent concurrent ablation, had extrahepatic disease, underwent a debulking operation, or had mixed anatomic and non-anatomic resections. Overall (OS) and recurrence-free (RFS) survival were compared among patients based on the extent of liver resection (AR vs. NAR). Results: Most primary tumors were located in the pancreas (n = 117, 45.4%) or the small intestine (n = 65, 25.2%). Liver resection consisted of NAR (n = 126, 48.8%) or AR (n = 132, 51.2%) resection. The overwhelming majority of patients who underwent NAR had an estimated liver involvement of < 50% (NAR 109, 97.3% vs. AR n = 82, 65.6%; P < 0.001). Patients who underwent NAR also had higher rates of primary tumor lymph node metastasis (NAR n = 79, 71.2% vs. AR n = 37, 33.6%; P < 0.001) and microscopically positive margins (R1) (NAR n = 29, 25.7% vs. AR n = 16, 12.5%; P = 0.009). After a median follow-up of 47.7 months, 48 (18.6%) patients died and 37.0% (n = 95) had evidence of disease recurrence. Patients who underwent AR had both longer median OS (not reached) and RFS (not reached) versus patients who underwent NAR (median OS 138.3 months; median RFS 31.3 months) (both P < 0.01). After controlling for patient and disease-related factors, extent of liver resection was independently associated with an increased risk of recurrence (HR 2.39, 95% CI 1.04-5.48; P = 0.04) but not death (HR 1.92, 95% CI 0.40-9.28; P = 0.42). Conclusion: NAR was independently associated with a higher incidence of recurrence versus patients who undergo a formal anatomic hepatectomy among patients with NELM. info:eu-repo/semantics/publishedVersion

BACKGROUND AND OBJECTIVES Gastrointestinal stromal tumors (GIST) are the most common sarcoma arising from the gastrointestinal tract. Data regrading long-term prognosis based on tumor location (stomach vs small intestine) are mixed, so we aimed to analyze their outcomes using a large national oncology database. METHODS The National Cancer Database was queried for cases of stomach and small intestine GIST between the years 2004 and 2014. Survival analysis was performed using the Kaplan-Meier method, and factors related to survival were compared using the Cox proportional hazards model. RESULTS Of 18 900 total patients, those with small intestine GIST had larger median tumor size (6.2 cm; interquartile range [IQR], 3.8 to 10.0 vs stomach: 5.0 cm; IQR, 3.0 to 9.0; P

Objective: Based on emerging data on tumor heterogeneity and the evolutionary branching of tumor cells, tumor cells in the lymph node may represent more virulent clones with the inherent capability of metastasis. IHC discordance from original cancer diagnosis to recurrence is documented to occur in up to 20% of cases, raising the question if characterization of these likely more virulent cells would more accurately guide treatment and predict prognosis. Our pilot study sought to determine if crucial clinical information is gained by IHC testing of the surgical breast or lymph node specimens at the time of initial surgery. Methods: Using the cancer registry and oncology records, all invasive breast cancers diagnosed after 2001 with subsequent recurrence were identified. Cases missing all IHC data were disqualified. We then evaluated ER and HER2 of the primary cancer biopsy and recurrence biopsy to identify discordances. Those with discordances who had surgical breast and lymph node specimens available were accessed, tested, and evaluated by our breast cancer pathologist. Results: A total of 128 recurrence cases with partial or complete primary and recurrence IHC data were identified. Of the 95 initially ER positive cases with recurrence IHC available, 13/95 had discordant, or ER negative, recurrence. Additionally, 5/27 initially ER negative tumors, 3/14 initially HER2 positive tumors, and 6/69 initially HER2 negative tumors had discordant recurrence results. In 128 cases, 27 cases were identified to have ER or HER2 discordance from primary biopsy diagnosis to recurrence. Of all cases with original surgical breast or positive lymph node specimen available, 9 markers on 7 patients were performed for our pilot study. One of seven surgical breast specimens and one of two lymph node specimens were concordant with the recurrence, but not the initial biopsy. The tested surgical breast was ER positive, while the surgical lymph node was HER2 positive, concordant to their recurrences, but discordant with initial biopsy. Breast BiopsyRecurrence ConcordantRecurrence DiscordantER Positive98/12782/9513/95 (14%)ER Negative29/12724/275/27 (19%) Total ER Discordance 18/122 (15%)HER2 Positive19/11911/143/14 (22%)HER2 Negative100/11963/696/69 (9%) Total HER2 Discordance 9/83 (11%) Conclusion: Tumor discordance of the original cancer biopsy and recurrence is not uncommon. Our pilot study demonstrated that ER and HER2 discordance occurred in 15% and 11% of cases, respectively. Though our pilot study was limited by small sample size, we found that IHC testing of the surgical breast and lymph node specimen may provide additional clinical information and affect management. Of the two cases that had a positive lymph node available, one was HER2 positive and concordant with the recurrence. Of the seven breast specimens tested, one was ER positive and concordant with the recurrence. Had IHC testing been performed at that time of surgery, adjuvant treatment management would have been altered. Further testing of our IHC discordant recurrence patient population will be pursued to investigate the potential benefits of surgical breast and lymph node IHC testing. Citation Format: Michele M Gage, Martin Rosman, Charles Mylander, Crystal Tran, Rubie S Jackson, Lorraine Tafra. Immunohistochemical (IHC) marker discordance between primary breast cancer biopsy and recurrent cancer: Would IHC testing of the surgical breast or lymph node have altered treatment? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-10.

Resection with clean margin (R0 resection) is associated with better survival in patients with pancreatic cancer. Over the last decade, advancements in preoperative chemotherapy and radiation therapy in pancreatic cancer have led to expansion of indications for surgical resection. Current guidelines define pancreatic cancer with unreconstructable vascular involvement as locally advanced, or surgically unresectable. We present our experience in managing patients with locally advanced pancreatic cancer with a very unique series of patients who achieved R0 resection despite "unresectable" vascular involvement. Additionally, we review current guidelines, the ability to predict venous resection by imaging, outcomes after venous resection and reconstruction, published patency rates of venous reconstructions, and potential future implications of this novel technique.

Predicting recurrence risk and chemotherapy benefit in early-stage breast cancer can be challenging, and Oncotype DX (ODX) is often used to gain insight. However, it is still unclear whether ODX can benefit in all cases. To clarify ODX's usefulness we sought to develop a model using readily available pathologic markers to help clinicians make that determination.Clinical pathologic data from 221 hormone receptor-positive, HER2-negative invasive breast cancer patients was used to create a model. The model was then validated on a second institution's set of 319 patients.The model has 2 simple rules: low grade and positive progesterone receptor tumors (LG+PR) are low risk, and high grade or low estrogen receptor (ER) (ER 20%) tumors (HG/LER) are high risk. The TAILORx (Trial Assigning Individualized Options for Treatment (Rx)) trial thresholds of Recurrence Score (RS) ≤ 10, when chemotherapy is of little benefit, and RS ≥ 26 when chemotherapy might be beneficial were used to judge model performance. Impressively, the misclassifications of an HG/LER patient who has an RS ≤ 10 were 0% and 2%, and for LG+PR patients who had an RS ≥ 26 were 0% and 2.6%. In the validation set, 28% (66 of 232) of the indeterminate group (neither in the HG/LER nor the LG+PR groups) had an RS ≤ 10 or an RS ≥ 26; this group might clinically benefit from ODX.A simple 2-rule model based on readily available pathologic data was developed and validated, which categorized patients into high and low risk for recurrence. Identification of patients who are unlikely to benefit from ODX testing could result in significant cost avoidance.

540 Background: Predicting recurrence risk and chemotherapy benefit in breast cancer can be challenging, and OncotypeDx (ODX) is often used to gain insight. Using readily available clinical informa...

559 Background: The gene expression profile assayOncotypeDx (ODX) is frequently used to guide adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive, lymph node (LN)-nega...