EP.WE.308COVID-19 and the impact on oncological surgery at a district general hospital

Introduction Covid-19 has had a significant impact on all aspects of healthcare. Efforts to maintain oncological surgery have continued throughout the pandemic despite facing significant challenges. We aimed to characterise our experience of oncological surgery during the first 2-months of the pandemic in Scotland and compare that with the same period in 2019. Methods A prospective cohort study was performed from 23/03/20 to 07/05/20. All elective oncological operations at a single district general hospital, predominantly managing breast and colorectal malignancies, were included. Data on patient demographics, waiting time to surgery, inpatient characteristics and oncological outcomes were recorded. Statistical analysis was used to compare these with retrospective data from 2019. Results A total of 37 patients were included, 18 in 2019 and 19 in 2020. There were no differences in patient age (63 vs 66.2 years, p = 0.486), length of stay (5.3 vs 4.3 days, p = 0.697) time spent on waiting list (25.4 vs 20.9 days, p = 0.303) or surgical approach (p = 0.300). Oncological outcomes were comparable with no statistical difference in clear resection margin status (88.9 vs 84.2%, p = 0.189) or positive nodal status (5.6 vs 26.3%, p = 0.086). No patient in either cohort had a post-operative complication. Conclusion Oncological surgery during Covid-19 can be performed safely and with favourable oncological outcomes. The longer-term effects from delayed diagnoses remain to be evaluated.

Acral Lentiginous Melanoma: A United States Multi-Center Substage Survival Analysis

Background Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care. Objectives To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients. Methods Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017. Results Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8–97] years; 53% female, 83% white), 66% presented with stage 0–2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0–259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, II = 76.2%, III = 63.4%, IIIA = 80.8%, and IV = 0%. Thicker Breslow depth ((HR) = 1.13; 95% CI = 1.05–1.21; P < .001)) and positive nodal status ((HR) = 1.79; 95% CI = 1.00–3.22; P = .050)) were independent prognostic factors for melanoma-specific survival. Breslow depth ((HR = 1.13; 95% CI = 1.07–1.20; P < .001), and positive nodal status (HR = 2.12; 95% CI = 1.38–3.80; P = .001) were also prognostic factors for recurrence-free survival. Conclusion In this cohort of patients, acral lentiginous melanoma was associated with poor outcomes even in early stage disease, consistent with prior reports. Stage IIB and IIC disease were associated with particularly low melanoma-specific and recurrence-free survival. This suggests that studies investigating adjuvant therapies in stage II patients may be especially valuable in acral lentiginous melanoma patients.

Predictors of Lymph Node Metastasis in Siewert Type II T1 Adenocarcinoma of the Esophagogastric Junction: A Population-Based Study

Background: Endoscopic resection has been introduced as an alternative treatment for superficial adenocarcinoma of the esophagogastric junction (AEG), but is limited by positive nodal status. We aimed to investigate the predictors of lymph node metastasis (LNM) in patients with Siewert type II T1 AEG. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify eligible patients with Siewert type II T1 AEG. The prevalence of LNM was assessed. Logistic regression analysis with multivariable adjustment was used to determine predictors of LNM. We also performed Cox regression analysis to examine the prognostic value of LNM, which was further confirmed by competing risk analysis and cumulative incidence function (CIF). Results: In total, 2651 patients with T1 AEG were included, with a median age of 69 years and a median follow-up of 28 months. The overall prevalence of LNM was 17.2% in T1 AEG. When stratified by tumor invasion depth, the prevalence of LNM was 8.5% for intramucosal tumors and 22.6% for submucosal tumors. Adjusted logistic regression analysis showed that age, sex, tumor grade, tumor size and tumor infiltration depth were independent predictors of LNM in T1 AEG. Multivariate Cox regression analysis revealed that positive nodal status was significantly associated with worse overall survival and cancer-specific survival (CSS). Subgroup analysis consistently demonstrated that patients with LNM had significantly poorer CSS than those without LNM in most subgroups. Finally, the CIF was calculated, showing that patients with LNM had a significantly higher cancer-specific death rate than those without LNM. Conclusions: This population-based study identified age, sex, tumor grade, tumor infiltration depth and tumor size as independent predictors of LNM in T1 AEG. Considering the high prevalence of LNM in T1 AEG, endoscopic resection for curative aims may only be introduced in patients without high risks of LNM.

Treatment Options for T1 Stage Adenocarcinoma of Esophagogastric Junction: A Real-World Retrospective Cohort Study

Background The number of patients diagnosed with T1 stage adenocarcinoma of esophagogastric junction (AEGJ) has been increasing. This study was conducted to investigate the effect of different treatment options (surgery, chemoradiation, and surgery+chemoradiation) on long-term survival in patients with T1-stage AEGJ. Methods We searched the Surveillance, Epidemiology, and End Results (SEER) database to identify the records of patients with T1-stage AEGJ between 2010 and 2018. Patient demographics and cancer parameters were compared among the three groups. The Kaplan–Meier method and Cox proportional hazard modeling were used to compare long-term survival. Results Data from 925 T1 stage AEGJ patients (surgery: n=516, surgery+chemoradiation: n=206, chemoradiation: n=203) were collected. We found that the OS and CSS rates of three treatment options had significant difference. Besides, positive nodal status also showed lower OS and CSS rat. Multivariate Cox regression analysis showed that surgery group has much lower risk of death compared with chemoradiation group and similar risk of death compared with surgery+chemoradiation group. Subgroup analysis suggested that in patients with N1–N3 status had higher OS and CSS rates in surgery+chemoradiation group. Conclusion Using SEER data, we identified a significant survival advantage with the use of surgery compared to chemoradiation in patients with T1-stage AEGJ while the long-term survival of patients after surgery+chemoradiation group was not significantly different and low risk of death in positive nodal status.

Proposal of a Panel of Genes Identified by miRNA Profiling as Candidate Prognostic Biomarkers in Lung Carcinoids

<b><i>Aim:</i></b> To validate the prognostic role of a panel of genes previously uncovered by our group to be specific targets of miRNAs differentially expressed in lung carcinoids with aggressive pathological features. <b><i>Methods:</i></b> Four genes, namely, cyclic AMP response element binding protein-1 (<i>CREBP1</i>), activin A receptor type 2B (<i>ACVR2B</i>), LIM homeobox 2 (<i>LHX2</i>), and Krüppel-like factor 12 (<i>KLF12</i>), were identified in a previous study by our group using in silico analysis to be regulated by 3 miRNAs (miR-409-3p, miR-409-5p, and miR-431-5p) that were shown to be downregulated in aggressive lung carcinoids. These genes were analyzed using real-time PCR in a cohort of 102 lung carcinoids. Fifty high-grade lung carcinomas served as control group. Their expression was correlated with the expression of miR-409-3p, miR-409-5p, and miR-431-5p and with clinical pathological parameters and disease-free survival. <b><i>Results:</i></b> The expression of all but <i>CREBP1</i> gene was significantly different between lung carcinoids and high-grade neuroendocrine carcinomas. <i>ACVR2B</i> and <i>LHX2</i> were significantly inversely correlated with miR-409-3p and miR-409-5p. High levels of <i>ACVR2B</i> and <i>LHX2</i> were significantly associated with atypical histotype, high tumor grade, and higher proliferation Ki-67 index (all <i>p</i> &#x3c; 0.05). Low levels of <i>KLF12</i> were significantly associated with the presence of necrosis and positive nodal status (all <i>p</i> &#x3c; 0.05). Finally, low <i>KLF12</i> expression was associated with shorter disease-free survival in lung carcinoids as a whole and in atypical carcinoids, only (all <i>p</i> &#x3c; 0.001). <b><i>Conclusions:</i></b> <i>ACVR2B</i>, <i>LHX2</i>, and <i>KFL12</i> are novel potential biomarkers associated with aggressive features in lung carcinoids.

Neoadjuvant chemotherapy versus upfront resection in ampullary adenocarcinoma stratified by stage: A retrospective analysis using the National Cancer Database.

318 Background: Outcomes of a neoadjuvant therapy (NAT) strategy to treat ampullary adenocarcinoma (AAC) are unclear. Upfront resection (UR) (typically pancreaticoduodenectomy) with or without adjuvant therapy (AT) is currently the standard of care. We looked to assess outcomes of NAT followed by radical surgery for AAC. Methods: The NCDB was queried for ampullary carcinoma patients from 2004-2015. Patients with Stage I to III AAC who underwent radical surgery were included, and separated into NAT with surgery and UR groups. Demographic/clinical/pathologic data and their associations to survival were analyzed with univariate and multivariate cox proportional hazard models. Overall survival was estimated from time of diagnosis using Kaplan-Meier curves and compared using log-rank tests (LRT) (see table). Statistical analyses were performed using R version 3.5.1 with significance established at p < 0.05. Results: There was no difference in overall survival between the NAT (n = 47) and UR (n = 1521) groups, either as total groups (LRT p = 0.2), or when stratified by stage (stratified LRT p = 0.5). Rates of AT were higher in the UR group (p = 0.038). Receiving AT was significantly associated with improved survival (hazard ratio (HR) = 0.648), while positive nodal status (HR = 2.06), stage 3 disease (HR = 1.542), age > 65 (HR = 1.494), and male gender (HR = 1.241) were significantly associated with decreased overall survival by multivariate analysis. Conclusions: NAT does not offer a survival advantage over UR either overall or for stage-specific disease. This finding extended even to stage III disease, where NAT would theoretically offer greatest benefit. This study suggests that a NAT strategy is not preferable to UR for treatment of resectable AAC, regardless of stage. Higher powered study of NAT for AAC with controls for AT is warranted before discarding a NAT strategy. [Table: see text]

Assessment of Aurora a Kinase Expression in Breast Cancer: A Tool for Early Diagnosis?

Aurora A kinase is overexpressed in many cancers but the status of this protein in the breast cancer often varies. We investigate the expression and localization of Aurora A protein in relation with tumor emergence and progression in breast cancer. Aurora A kinase status was evaluated in 107 patients using immunohistochemistry. The experimental findings showed that high expression of the Aurora A protein was correlated with elevated nuclear grade, low expression of progesterone receptor and positive nodal status. The experimental results showed also that the localization of this kinase shifts from cytoplasm in non malignant adjacent tissue to both cytoplasmic and nuclear compartments in tumoral tissue, suggesting an oncogenic role of the nuclear accumulation. We have, furthermore, detected the overexpression of this protein in non malignant adjacent tissue. The expression of the Aurora A kinase in non malignant tissue may represent an earlier diagnosis tool for breast cancer.

Biological Characteristics and Medical Treatment of Breast Cancer in Young Women—A Featured Population: Results from the NORA Study

Background. The present paper described the biological characteristics and clinical behavior of young women in the cohort NORA studyPatients and Methods. From 2000–2002, patients () were enrolled at 77 Italian hospitals. Women aged years () were stratified into age groups (, 36–40, 41–45, and 46–50 years). The relationship between age and patient characteristics, cancer presentation, and treatment was analyzed.Results. Younger women more frequently had tumors with ER/PgR-negative(; ), HER2 amplification (; ), and high () Ki67 labelling index (; ). Positive nodal status, large tumors, and elevated Ki67 all associated with the choice for chemotherapy followed by endocrine therapy in hormone receptor-positive patients (). At univariate analysis, ER-ve status, chemotherapy and age resulted as the only statistically significant variables (, , and versus , , resp.). At multivariate analysis, after adjustment for significant clinical and pathological factors, age remains a significant prognostic variable (, ).Conclusion. This cohort study suggests that ageper sèis an important prognostic factor. The restricted role of early diagnosis and the aggressive behavior of cancer in this population make necessary the application of targeted medical strategies crucial.