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Purpose: Rectal cancer is often clinically resistant to radiotherapy (RT) and identifying molecular markers to define the biologic basis for this phenomenon would be valuable. The nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) is a potential anti-apoptotic transcription factor that has been associated with resistance to RT in model systems. The present study was designed to evaluate NF-κB activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-κB activity correlates with the outcome in rectal cancer patients.Methods and Materials: A total of 22 patients underwent biopsy at multiple points in a prospective study and the data from another 50 were analyzed retrospectively. The pretreatment tumor tissue was analyzed for multiple NF-κB subunits by immunohistochemistry. Serial tumor biopsy cores were analyzed for NF-κB-regulated gene expression using reverse transcriptase polymerase chain reaction and for NF-κB subunit nuclear localization using immunohistochemistry.Results: Several NF-κB target genes (Bcl-2, cellular inhibitor of apoptosis protein [cIAP]2, interleukin-8, and tumor necrosis factor receptor-associated-1) were significantly upregulated by a single fraction of RT at 24 h, demonstrating for the first time that NF-κB is activated by RT in human rectal tumors. The baseline NF-κB p50 nuclear expression did not correlate with the pathologic response to RT. However, an increasing baseline p50 level was prognostic for overall survival (hazard ratio, 2.15; p = .040).Conclusion: NF-κB nuclear expression at baseline in rectal cancer was prognostic for overall survival but not predictive of the response to RT. Larger patient numbers are needed to assess the effect of NF-κB target gene upregulation on the response to RT. Our results suggest that NF-κB might play an important role in tumor metastasis but not to the resistance to chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Objective: To assess the utility of tumor-intrinsic and cancer-associated fibroblast (CAF) subtypes of pancreatic ductal adenocarcinoma (PDAC) in predicting response to neoadjuvant therapy (NAT) and overall survival (OS)., Background: PDAC remains a deadly disease with limited treatment options, and both the tumor as well as the microenvironment play an important role in pathogenesis. Gene expression-based tumor-intrinsic subtypes (classical and basal-like) have been shown to predict outcomes, but tumor microenvironment subtypes are still evolving., Methods: RNA-sequencing was performed on 114 deidentified resected PDAC tumors. Clinical data were collected by retrospective chart review. Single sample classifiers were used to determine classical and basal-like subtypes as well as tumor-permissive permCAF and tumor-restraining restCAF subtypes. Survival was analyzed using the log-rank test., Results: Patients who received NAT had an increase in OS, with a median survival of 27.9 months compared with 20.1 months for those who did not receive NAT, but the difference did not reach statistical significance (hazard ratio: 0.64, P =0.076). Either tumor-intrinsic or CAF subtypes alone were associated with OS regardless of NAT or no NAT, and patients with classical or restCAF subtypes had the best outcomes. When evaluated together, patients with the classical-restCAF subtype had the best OS and basal-permCAF the worst OS ( P <0.0001). Patients undergoing NAT with the classical-restCAF subtype demonstrated the longest OS compared with the other groups ( P =0.00041)., Conclusions: CAF subtypes have an additive effect over tumor-intrinsic subtypes in predicting survival with or without neoadjuvant FOLFIRINOX in PDAC. Molecular subtyping of both tumor and CAF compartments of PDAC may be important steps in selecting first-line systemic therapy., Competing Interests: J.J.Y., X.,L.,P., and N.U.R. are inventors of PurIST Subtype Classifier, which was licensed to GeneCentric Therapeutics, Inc. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic herpesvirus therapy used for unresectable stage IIIB through IV metastatic melanoma. However, the correlation between clinical complete response (cCR) and pathologic complete response (pCR) in patients treated with T-VEC is understudied., Study Design: We conducted a retrospective study from a prospectively maintained IRB-approved melanoma single-center database in patients treated with T-VEC from October 2015 to April 2022. Patients were categorized into 3 groups: cCR with pCR, cCR without pCR, and less than cCR. The primary endpoint was overall survival. We used descriptive statistics, chi-square tests, and Wilcoxon rank-sum tests to compare key covariates among exposure groups. We used survival analysis to compare survival curves and reported hazard ratio of death (95% CI) across exposure groups., Results: We included 116 patients with a median overall survival (interquartile range) of 22.7 (14.8-39.3) months. The majority were men (69%) and White (97.4%), with a median age of 74.5 years. More than half of patients (n = 60, 51.6%) achieved cCR. Distribution among the groups was as follows: cCR with pCR (35.3%), cCR without pCR (16.3%), and less than cCR (48.4%). Median overall survival time (interquartile range) was 26.5 (18.6-36.0) months for cCR with pCR, 22.7 (14.4-35.5) months for cCR without pCR, and 17.8 (9.2-47.0) months for less than cCR (log-rank p value = 0.0033)., Conclusions: Patients achieving cCR with pCR after T-VEC therapy have the most favorable overall survival outcomes, whereas those achieving cCR without pCR have inferior survival and those achieving less than cCR have the poorest overall survival outcomes. These findings emphasize the importance of histological confirmation and provide insights for optimizing T-VEC therapy in patients with advanced melanoma., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Children, adolescents, and young adults (CAYA) (age ≤39 years) with GIST have high rates of LNM, but their clinical relevance is undefined. This study analyzed the impact of LNM on overall survival (OS) for CAYA with GIST., Methods: The National Cancer Database was queried for patients with resected GIST and pathologic nodal staging data from 2004-2019. Factors associated with LNM were identified. Survival was assessed stratified by presence of LNM., Results: Of 4420 patients with GIST, 238 were CAYA (5.4%). When compared to older adults, CAYA more often had small intestine primaries (51.8% vs. 36.6%, p < 0.0001), T4 tumors (30.7% vs. 24.5%, p = 0.0275) and pN1 disease (11.3% vs. 4.7%, p < 0.0001). Within a multivariable Cox proportional hazards regression model adjusting for age, comorbid disease, mitotic rate, tumor size, and primary site, LNM were associated with increased hazard of death for older adults (hazard ratio [HR]: 1.83; confidence interval [CI]: 1.35-2.42; p < 0.0001), but not CAYA (HR: 3.38; CI: 0.50-14.08; p = 0.13). For CAYA, only high mitotic rate predicted mortality (HR: 4.68; CI: 1.41-18.37: p = 0.02)., Conclusions: LNM are more commonly identified among CAYA with resected GIST who undergo lymph node evaluations, but do not appear to impact OS as observed in older adults. High mitotic rate remains a predictor of poor outcomes for CAYA with GIST., (© 2023 Wiley Periodicals LLC.)

Purpose: To provide guidance to clinicians regarding the use of systemic therapy for melanoma., Methods: American Society of Clinical Oncology convened an Expert Panel and conducted an updated systematic review of the literature., Results: The updated review identified 21 additional randomized trials., Updated Recommendations: Neoadjuvant pembrolizumab was newly recommended for patients with resectable stage IIIB to IV cutaneous melanoma. For patients with resected cutaneous melanoma, adjuvant nivolumab or pembrolizumab was newly recommended for stage IIB-C disease and adjuvant nivolumab plus ipilimumab was added as a potential option for stage IV disease. For patients with unresectable or metastatic cutaneous melanoma, nivolumab plus relatlimab was added as a potential option regardless of BRAF mutation status and nivolumab plus ipilimumab followed by nivolumab was preferred over BRAF/MEK inhibitor therapy. Talimogene laherparepvec is no longer recommended as an option for patients with BRAF wild-type disease who have progressed on anti-PD-1 therapy. Ipilimumab- and ipilimumab-containing regimens are no longer recommended for patients with BRAF -mutated disease after progression on other therapies.This full update incorporates the new recommendations for uveal melanoma published in the 2022 Rapid Recommendation Update.Additional information is available at www.asco.org/melanoma-guidelines.

Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov, NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors ( n  = 68). Melanoma cell-specific TPH1 and LAT1 expressions were significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cutpoint survival analysis of pretreatment 'high' vs. 'low' C11-AMT SUV max of the hottest tumor lesion per patient revealed that the 'low' C11-AMT SUV max was associated with longer progression-free survival in our clinical trial ( n  = 26). We saw no such trends with pretreatment FDG PET SUV max . Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid., Competing Interests: Funding for the LCCC1531 trial was provided by Merck & Co., Inc., (© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Context: Burnout remains prevalent among surgical residents. Self-compassion training may serve to improve their well-being., Objective: To evaluate the impact on well-being of a self-compassion program modified for surgical residents., Design: This is a 3-year, mixed-methods study using pre-post surveys and focus groups to identify areas for programmatic improvement and the subsequent impact of the modifications., Setting: A single academic institution., Participants: Surgical residents participating in a self-compassion program., Interventions: A self-compassion program adapted from a larger course to fit the needs of surgical residents., Main Outcome Measures: Themes relating to the program's strengths and weaknesses were identified through participant focus groups. Well-being was assessed through validated measurement tools, including The Maslach Burnout Inventory (MBI), Patient Health Questionnaire-9, Perceived Stress Scale, and Spielberger State-Trait Anxiety Inventory-6., Results: 95 residents participated in the self-compassion program, of which 40 residents completed both surveys (total response rate: 42%). All participants demonstrated severe burnout pre-program, based on scores of at least one of the MBI subscales. Emotional exhaustion scores improved post-program, with larger improvements seen after program modifications (2018: 58% vs 2020: 71%). Focus group findings demonstrated that residents need a safe and distraction-free space to practice self-compassion, and program engagement improved following modifications., (Published by Elsevier Inc.)

Background and Objectives: Disparities in esophageal cancer are well-established. The standard treatment for locally advanced esophageal cancer is chemoradiation followed by surgery. We sought to evaluate the association between socioeconomic factors, time to surgery, and patient outcomes., Methods: All patients ≥18 years old diagnosed with T2/3/4 or node-positive esophageal cancer between 2004 and 2016 and who underwent chemoradiation and esophagectomy in the National Cancer Database were included. Multivariable regression was used to assess the association between socioeconomic variables and time to surgery (grouped into <56, 56-84, and 85-112 days)., Results: A total of 12 157 patients were included. Five-year overall survival was 39%, 35%, and 35% for the three groups examined. Postoperative 30- and 90-day mortality was increased in both the 56-84 days to surgery group (odds ratio [OR]: 1.30 and 1.20, respectively) and the 85-112 days group (OR: 1.37 and 1.56, respectively) when compared to <56 days. Patients of a minority race, public insurance, or lower income were more likely to have a longer time to surgery., Conclusion: Longer time to surgery is associated with increased postoperative mortality and is more common in patients with lower socioeconomic status. Further research exploring reasons for delays to esophagectomy among disadvantaged patients could help target interventions to reduce disparities., (© 2021 Wiley Periodicals LLC.)

Purpose: To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma., Methods: After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy., Results: Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached., Conclusion: Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%., Competing Interests: Karyn A. GoodmanConsulting or Advisory Role: RenovoRx Tanios Bekaii-SaabConsulting or Advisory Role: Amgen, Ipsen, Lilly, Bayer, Roche/Genentech, AbbVie, Incyte, Immuneering, Seattle Genetics, Pfizer, Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation MedicinePatents, Royalties, Other Intellectual Property: Patent WO/2018/183488 and Patent WO/2019/055687Other Relationship: Exelixis, Merck, AstraZeneca, Lilly, Pancreatic Cancer Action Network Daniel J. BoffaResearch Funding: Epic Sciences Wendy L. FrankelPatents, Royalties, Other Intellectual Property: Patent title: Automated Identification of Tumor Buds. Application No.: 16/230,118. Filing date: December 21, 2018. Publication date: July 4, 2019. Applicant(s): Ohio State Innovation Foundation, Columbus, OH. Inventor(s): Metin Gurcan, Winston-Salem, NC; Wendy Frankel, Columbus, OH; Wei Chen, Columbus, OH; Ahmad Fauzi and Mohammad Faizal, Selangor, MY Anne NoonanConsulting or Advisory Role: Helsinn Healthcare, QED Therapeutics, Exelixis, Eisai Yelena Y. JanjigianStock and Other Ownership Interests: RgenixConsulting or Advisory Role: Pfizer, Merck, Bristol Myers Squibb, Merck Serono, Daiichi Sankyo, Rgenix, Bayer, Imugene, AstraZeneca, Lilly, Zymeworks, Seattle Genetics, Merck Sharpe and Dohme Corp, Michael J. Hennessy Associates, Jounce Therapeutics, Ono PharmaceuticalResearch Funding: Boehringer Ingelheim, Bayer, Roche, Genentech, Rgenix, Bristol Myers Squibb, Merck, LillyOther Relationship: Paradigm, Clinical Care Options, Axis Medical Education, Research to Practice Paul J. ThurmesConsulting or Advisory Role: US OncologyTravel, Accommodations, Expenses: US Oncology Alan P. VenookConsulting or Advisory Role: Merck Sharp & Dohme, Array BioPharmaResearch Funding: Genentech/Roche, Bristol Myers Squibb, AmgenPatents, Royalties, Other Intellectual Property: Royalties from Now-UptoDate for authoring and maintaining two chaptersTravel, Accommodations, Expenses: Genentech, Roche Jeffrey A. MeyerhardtHonoraria: Cota Healthcare, Taiho PharmaceuticalResearch Funding: Boston Biomedical Eileen M. O'ReillyConsulting or Advisory Role: Merck, Agios, AstraZeneca, Bayer, BeiGene, Berry Genomics, Celgene, CytomX Therapeutics, Debiopharm Group, Eisai, Exelixis/Ipsen, Flatiron Health, Incyte, Janssen, LAM Therapeutics, Lilly, Loxo, Genentech/Roche, Minapharma, QED Therapeutics, RedHill Biopharma, Sillajen, SOBI, Yiviva, Autem Medical, Gilead Sciences, Ipsen, Silenseed, TheraBionic, twoXAR, Vector HealthResearch Funding: AstraZeneca/MedImmune, Acta Biologica, Bristol Myers Squibb, Celgene, Genentech, Halozyme, MabVax, Roche, Silenseed David H. IlsonConsulting or Advisory Role: Lilly/ImClone, Roche/Genentech, Bristol Myers Squibb, Pieris Pharmaceuticals, Merck, Bayer, AstraZeneca, Taiho Pharmaceutical, Astellas Pharma, IQvia, MacrogenicsNo other potential conflicts of interest were reported.

Background: The utility of sentinel lymph node biopsy (SLNB) for non-ulcerated T1b melanoma is debated and associated costs are poorly characterized. Prior work using institutional registries may overestimate the incidence of nodal positivity in this population., Objective: The aim of this study was to estimate the use of SLNB, positivity prevalence, and procedural costs in patients with non-ulcerated T1b melanoma using a population-based registry., Methods: We identified patients with clinically node-negative, non-ulcerated melanoma 0.8-1.0 mm thick (T1b according to the 8th edition standard of the American Joint Committee on Cancer) in the Surveillance, Epidemiology, and End Results database from 2010 to 2016. The prevalence of SLNB procedures and positive sentinel nodes were calculated. Factors associated with SLNB and sentinel node positivity were assessed using logistic regression. Medicare reimbursement costs and patient out-of-pocket expenses for SLNB and wide local excision (WLE) versus WLE alone were estimated., Results: Among 7245 included patients, 3835(53%) underwent SLNB, 156 (4.1%, 95% confidence interval 3.5-4.7) of whom had a positive SLNB. Younger age, >1 mitosis per mm 2 , female sex, and truncal tumor location were associated with higher odds of positivity. The estimated SLNB cost to identify one patient with stage III disease was $71,700 (range $54,648-$83,172). Out-of-pocket expenses for a Medicare patient were estimated to be $652 for a WLE and SLNB and $79 for a WLE alone., Conclusions: In this population-based study, only 4% of selected non-ulcerated T1b patients had a positive SLNB, which is lower than prior reports. At the population level, SLNB is associated with high costs per prognostic information gained.

Objective: Gender bias has been identified in letters of recommendation (LOR) in many different surgical training fields. Among surgeons, women comprise over 30% of the full-time faculty positions nationally and surgical oncology is one of the most gender diverse surgical subspecialties. We sought to determine if bias existed in LOR submitted to a Complex General Surgical Oncology (CGSO) fellowship., Design: LOR for the CGSO fellowship were retrospectively analyzed from applicants at a single institution over an 8-year period (2013-2020). The linguistic content of the letters was analyzed using Linguistic Inquiry and Word Count (LIWC2015), a validated text analysis program. Using multivariable analysis, LOR were compared by gender of both applicant and letter writer to explore the association between gender and the characteristics of the applicants and letter writers., Setting: University of North Carolina at Chapel Hill (UNC), Division of Surgical Oncology and Endocrine Surgery., Participants: Applicants interviewed for the CSGO fellowship program at the UNC from 2013 to 2020 as well as all applicants from the 2018 application cycle, regardless of interview status., Results: About 841 letters from 219 interviewed applicants throughout the 2013 to 2020 surgical oncology fellowship application cycles were included. No difference in authenticity, clout, analytic thinking, or emotional tone of the letters was seen when comparing men and women applicants. Of the 41 word categories analyzed, only "references to achievement" in LOR written for women was significantly higher when compared to LOR written for men (p = 0.01). Interestingly, significantly more women applicants had at least 1 LOR written by a woman (p = 0.04). A subset analysis of all applicants regardless of interview status from the 2018 cycle included 294 LOR from 77 applicants. With the inclusion of noninterviewed applicants, LOR for men had more analytic tone than LOR for women (p = 0.02), otherwise there were no significant differences between the groups., Conclusions: Very few differences in LOR were found for applicants at a CGSO fellowship program based on applicant or letter writer gender. The lack of gender bias demonstrates progress within the field of surgical oncology, likely a result of recent work and educational effort in this area. Efforts to expand this progress into other surgical sub-specialties are necessary., (Copyright © 2020. Published by Elsevier Inc.)

Background: In the era of coronavirus disease 2019 (COVID-19), many Complex General Surgical Oncology (CGSO) fellowship programs implemented virtual interviews (VI) during the 2020 interview season. At our institution, we had the unique opportunity to conduct an in-person interview (IPI) prior to the pandemic-related travel restrictions, and a VI after the restrictions were in place., Objective: The goal of this study was to understand how the VI model compares with the traditional IPI approach., Methods: Online surveys were distributed to both groups, collecting feedback on their interview experience. Responses were evaluated using a two-sample t test assuming equal variances., Results: Twenty-three of 26 (88%) applicants completed the survey. Most applicants reported that the interview gave them a satisfactory understanding of the CGSO fellowship (100% IPI, 92% VI) and the majority in both groups felt that the interview experience allowed them to accurately represent themselves (92% and 82%, respectively). All participants in the IPI group felt they were able to get an adequate understanding of the culture of the program, while only 64% in the VI group agreed with that statement (p = 0.02). IPI applicants were more likely to agree that the interview experience was sufficient to allow them to make a ranking decision (92% vs. 54%; p = 0.04)., Conclusions: While the VI modality offers several advantages over the IPI, it still falls short in conveying some of the more subjective aspects of the programs, including program culture. Strategies to provide applicants with better insight into these areas during the VI will be important moving forward.

Background: Melanoma-specific outcomes for Black patients are worse when compared to non-Hispanic white (NHW) patients. We sought to evaluate whether acral lentiginous melanoma, seen more commonly in Black patients, was associated with racial disparities in outcomes METHODS: The National Cancer Database was analyzed for major subtypes of stage I-IV melanoma diagnosed from 2004 to 2016. The association between Black race and (Siegel et al., Jan) 1 acral melanoma diagnosis and (Bradford et al., Apr) 2 receipt of major amputation for surgical management of melanoma was evaluated using multivariable logistic regression., Results: 251,864 patients were included (1453 Black). Black patients had increased odds of acral melanoma (odds ratio [OR] = 27.6, 95% CI]: 24.4, 31.2) compared to NHW patients. Black patients still had higher odds ratios of major amputation across all stages after adjusting for acral histology and other potential confounders CONCLUSIONS: Increased prevalence of acral melanoma in Black patients does not fully account for increased receipt of major amputation., (Copyright © 2020. Published by Elsevier Inc.)

Background: Studies have shown poorer health outcomes for people who identify as sexual and/or gender minority (LGBTQ+) compared to heterosexual peers. Our goal was to establish baseline levels of LGBTQ Ally Identity Measure (AIM) scores: (1) Knowledge and Skills, (2) Openness and Support, and (3) Awareness of Oppression of the LGBTQ+ in surgical trainees, and implement a pilot training in LGBTQ + cultural competency., Materials and Methods: General surgery residents from a single academic medical center participated in a 2-h educational training developed from the existing Health Care Safe Zone training at our institution. Utilizing the previously validated LGBTQ Ally Identity Measure (AIM), residents responded to 19 items on Likert-type scales from 1 to 5 pretraining and 6 wk posttraining. The residents' perceptions of the utility of the training were also assessed. Data were analyzed by MANOVA, repeated measures MANOVA, and subsequent univariate analysis., Results: 27 residents responded to the pretraining survey (52%), 22 residents participated in the training, and 10 responded at 6 wk posttraining (19%). The average baseline scores were Knowledge and Skills 19.38 ± 4.64, Openness and Support 25.96 ± 4.31, and Awareness of Oppression 17.15 ± 2.20. Participants who identified as women scored 4.46 (95% CI 0.77-8.15) points higher in Openness and Support compared to males. Of those respondents who completed pretraining and posttraining surveys (n = 10), training had a significant effect on AIM scores with an improvement in Knowledge and Skills (P = 0.024) and Openness and Support (P = 0.042). Residents found the training relevant to surgery patient care (71%), increased their competency in LGBTQ + patient care (86%), and all participants indicated they were better LGBTQ allies following the training., Conclusions: Assessing LGBTQ + allyship in surgical residents, we found that training improved AIM scores over time with significant improvement in the Knowledge and Skills, and Openness and Support scales, suggesting a viable and valuable curriculum focused on sexual and gender identity-related competencies within the graduate medical education for surgical trainees., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To provide guidance to clinicians regarding the use of systemic therapy for melanoma., Methods: ASCO convened an Expert Panel and conducted a systematic review of the literature., Results: A systematic review, one meta-analysis, and 34 additional randomized trials were identified. The published studies included a wide range of systemic therapies in cutaneous and noncutaneous melanoma., Recommendations: In the adjuvant setting, nivolumab or pembrolizumab should be offered to patients with resected stage IIIA/B/C/D BRAF wild-type cutaneous melanoma, while either of those two agents or the combination of dabrafenib and trametinib should be offered in BRAF -mutant disease. No recommendation could be made for or against the use of neoadjuvant therapy in cutaneous melanoma. In the unresectable/metastatic setting, ipilimumab plus nivolumab, nivolumab alone, or pembrolizumab alone should be offered to patients with BRAF wild-type cutaneous melanoma, while those three regimens or combination BRAF/MEK inhibitor therapy with dabrafenib/trametinib, encorafenib/binimetinib, or vemurafenib/cobimetinib should be offered in BRAF -mutant disease. Patients with mucosal melanoma may be offered the same therapies recommended for cutaneous melanoma. No recommendation could be made for or against specific therapy for uveal melanoma. Additional information is available at www.asco.org/melanoma-guidelines.

There are multiple transitions in surgical education. Among the most significant are those from medical student to intern, from junior resident to senior resident, and from senior resident/fellow to independent practice. While there are new expectations and responsibilities associated with each of these roles, a surgeon's development should be thought of as more of a continuum with distinct points of greatest change and challenge. There are common themes at these various transitions that may be highlighted for both trainees and educators., (Copyright © 2019. Published by Elsevier Inc.)

Background: For patients with sentinel node-positive melanoma (SNPM), randomized trials, first reported in 2015, found no benefit for routine completion lymph node dissection (CLND) in selected patients. This study examines time trends in CLND and explores institutional and clinical factors associated with CLND., Study Design: The National Cancer Database was queried for patients older than 18 years from 2012 to 2016 with SNPM. A high-volume center was defined as >80th percentile for number of sentinel node procedures. Poisson regression assessed temporal trends and identified patient, pathologic, and institutional characteristics associated with CLND., Results: From 2012 to 2016, we identified 7,146 patients with SNPM. The proportion of patients undergoing CLND was steady in 2012 to 2014 (61% to 63%), but decreased to 57% in 2015 and 50% in 2016 (p < 0.0001). The proportion of patients with SNPM who underwent CLND decreased over time for both high- (66% to 52%; p < 0.0001) and lower-volume centers (55% to 45%; p = 0.06). Female sex (relative risk [RR] 0.97; p < 0.001) and increasing age (RR 0.98; p < 0.0001) were associated with lower likelihood of CLND. Increased Breslow depth (RR 1.015; p = 0.006), ulceration (RR 1.067; p = 0.02), and high-volume centers (RR 1.180; p < 0.0001) were associated with higher likelihood of CLND. Regional differences in likelihood of CLND were also present (p < 0.0001)., Conclusions: Completion lymph node dissection in SNPM decreased over time, with the greatest change in 2016. Several patient, pathologic, and institutional characteristics were associated with likelihood of CLND. As evidence supports close observation for selected patients, efforts should be undertaken to improve and standardize patient selection for CLND across institutions caring for patients with melanoma., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Despite efforts at standardization, evaluation and reporting of clerkships remains highly variable. This study reviews the current spectrum of surgical clerkship grading., Methods: Data were reviewed for every medical school from which an application was received to a single surgery residency program in 2017 and were evaluated for core surgical clerkship grading systems, distributions, and components. Fischer's exact tests and Wilcoxon-Mann-Whitney tests were used for analysis., Results: 133 (49 private) schools were evaluated. Geographic distribution:34 Northeast, 50 South, 31 Midwest and 18 West. 120 reported grading tiers, with public schools (95%) more likely than private (80%) to report this (p = 0.02). The number of grading categories ranged from 2 to 11; 90% with 3-5. Over 25% of the schools gave ≥40% of students the highest grade; median of 30% in the highest tier., Conclusions: Significant variation exists in core surgery clerkship grading between schools. Similarly, a sizeable difference exists in how grades are calculated and the reporting systems used. Standardizing grading schemes across medical schools would be beneficial., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Prior studies demonstrate a high prevalence of burnout and depression among surgeons. Limited data exist regarding how these conditions are perceived by the surgical community., Objectives: To measure prevalence of burnout and depression among general surgery trainees and to characterize how residents and attendings perceive these conditions., Design, Setting, and Participants: This cross-sectional study used unique, anonymous surveys for residents and attendings that were administered via a web-based platform from November 1, 2016, through March 31, 2017. All residents and attendings in the 6 general surgery training programs in North Carolina were invited to participate., Main Outcomes and Measures: The prevalence of burnout and depression among residents was assessed using validated tools. Burnout was defined by high emotional exhaustion or depersonalization on the Maslach Burnout Inventory. Depression was defined by a score of 10 or greater on the Patient Health Questionnaire-9. Linear and logistic regression models were used to assess predictive factors for burnout and depression. Residents' and attendings' perceptions of these conditions were analyzed for significant similarities and differences., Results: In this study, a total of 92 residents and 55 attendings responded. Fifty-eight of 77 residents with complete responses (75%) met criteria for burnout, and 30 of 76 (39%) met criteria for depression. Of those with burnout, 28 of 58 (48%) were at elevated risk of depression (P = .03). Nine of 77 residents (12%) had suicidal ideation in the past 2 weeks. Most residents (40 of 76 [53%]) correctly estimated that more than 50% of residents had burnout, whereas only 13 of 56 attendings (23%) correctly estimated this prevalence (P < .001). Forty-two of 83 residents (51%) and 42 of 56 attendings (75%) underestimated the true prevalence of depression (P = .002). Sixty-six of 73 residents (90%) and 40 of 51 attendings (78%) identified the same top 3 barriers to seeking care for burnout: inability to take time off to seek treatment, avoidance or denial of the problem, and negative stigma toward those seeking care., Conclusions and Relevance: The prevalence of burnout and depression was high among general surgery residents in this study. Attendings and residents underestimated the prevalence of these conditions but acknowledged common barriers to seeking care. Discrepancies in actual and perceived levels of burnout and depression may hinder wellness interventions. Increasing understanding of these perceptions offers an opportunity to develop practical solutions.

Tumor mitotic rate (TMR) is a known prognostic variable in thin melanoma patients. Its significance in stage II melanoma patients is yet to be demonstrated. Retrospective analysis of a prospective melanoma database from 9/1997 to 7/2015 was performed. All stage II melanoma, with documented TMR, and six months of follow-up were included. We evaluated the association of clinicopathologic variables, TMR, as a continuous and categorical variable with recurrence-free survival (RFS) and overall survival (OS) using Cox proportional hazards modeling. We used a statistical model, X-tile, to develop optimal categorizations of TMR. A total of 265 patient characteristics are included in this study. Recurrences occurred in 82 (30.9%) patients, including 5 local, 41 regional, and 36 distant patients. In multivariate model, ulceration, Breslow, and continuous TMR were associated with worse RFS\OS. Continuous TMR demonstrated worse RFS (hazards ratio [HR] 1.02 (1.00-1.05)) and OS (HR 1.02 (1.00-1.04)), whereas dichotomized TMR (≥1 vs <1) was not significant. TMR >10.4 mitoses/mm2 has a 5-year RFS\OS of 27.2 and 44.3 per cent, respectively, compared with 57.4 and 71.4 per cent, respectively, for TMR <3.2 mitoses/mm2. Continuous TMR predicts incidence of recurrence in stage II melanoma. We propose a new categorization method developed by statistical modeling for optimal stratification that may guide surveillance for this disparate patient population.

Central line placement is a common procedure, routinely performed by junior residents in medical and surgical departments. Before this project, no standardized instructional course on the insertion of central lines existed at our institution, and few interns had received formal ultrasound training. Interns from five departments participated in a simulation-based central line insertion course. Intern familiarity with the procedure and with ultrasound, as well as their prior experience with line placement and their level of comfort, was assessed. Of the 99 interns in participating departments, 45 per cent had been trained as of October 2015. Forty-one per cent were female. The majority (59.5%) had no prior formal ultrasound training, and 46.0 per cent had never placed a line as primary operator. Scores increased significantly, from a precourse score mean of 13.7 to a postcourse score mean of 16.1, P < 0.001. All three of the self-reported measures of comfort with ultrasound also improved significantly. All interns reported the course was "very much" helpful, and 100 per cent reported they felt "somewhat" or "much" more comfortable with the procedure after attendance. To our knowledge, this is the first hospital-wide, standardized, simulation-based central line insertion course in the United States. Preliminary results indicate overwhelming satisfaction with the course, better ultrasound preparedness, and improved comfort with central line insertion.

Background: Patients with stage II melanoma have a considerable risk for recurrence. Current guidelines are imprecise as to optimal follow-up. We hypothesized that by examining recurrence patterns, we could help to better inform guidelines., Study Design: We queried IRB-approved melanoma databases of Thomas Jefferson University and University of North Carolina, identifying 581 patients with stage II melanoma between 1996 and 2015 with at least 1 year of follow-up. Data included location of first recurrence and how recurrence was detected (ie patient symptom, physician examination, or routine surveillance imaging). Cox regression with backward elimination was used for multivariable analysis., Results: One hundred and seventy-one patients had a recurrence (29.4%), the incidence increased considerably by stage sub-group. Significant predictors of recurrence included male sex (p = 0.003), ulceration (p = 0.03), and stage (p < 0.001). On multivariable analysis, male sex and stage continued to be significant (p < 0.01). For overall survival, regression, ulceration, stage, and age were significant predictors of survival. Stage, regression, and age remained significant by multivariable analysis. Patient symptoms were the most frequent mode of detection (40%), followed by physician examination (30%) and surveillance imaging (26%)-this did not differ significantly by stage. Regional nodes were the most common site of recurrence (30%), followed by lung (27%) and in-transit (18%)., Conclusions: The majority of recurrences in stage II melanoma are detected by patients and their physicians and rarely by routine imaging. As such, clinical follow-up and patient education are critical factors in detection of recurrence. With the prevalence of regional nodal recurrences, ultrasound might prove to be an important strategy in early recurrence detection., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

This article discusses the current National Comprehensive Cancer Network guidelines and other available Western and Eastern guidelines for the surveillance of gastric cancer following surgical resection. It reviews the literature assessing the utility of intensive surveillance strategies for gastric cancer, which fails to show an improvement in survival. The unique issues relating to follow-up of early gastric cancer and after endoscopic resection of early gastric cancer are discussed. This article also reviews the available modalities for follow-up. In addition, it briefly discusses the advancements in treatment of recurrent and metastatic disease and the implications for gastric cancer survival and surveillance strategies., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The burden of readmissions after major cancer surgery is high. Prior work suggests that one-third of readmitted patients are readmitted to a different hospital than where the surgery was performed. The impact of this location of readmission needs to be more thoroughly understood., Methods: This retrospective cohort study was performed on Surveillance, Epidemiology, and End Results (SEER)-Medicare patients with bladder, esophagus, lung, or pancreas cancer diagnosed from 2001 to 2007 who underwent extirpative surgery and were readmitted within 90 days. Readmission location was classified as 'index' if readmission was at the hospital where surgery was performed, or 'different' if readmission was elsewhere. Outcomes including complications, reoperations, in-hospital mortality, 90-day mortality, and 90-day total costs were compared based on the location of readmission using a propensity score inverse probability treatment weight analysis., Results: Overall, 7903 (28 %) patients were readmitted within 90 days of index hospitalization. Thirty-three percent were readmitted to a different hospital (bladder 30 %, esophagus 34 %, lung 34 %, pancreas 34 %). Ninety-day mortality and total costs of care were not significantly different between the readmission location groups (all p > 0.05); however, substantial differences in the types of patients, and timing of and reasons for readmission were observed between the two groups., Conclusions: Patients readmitted to different hospitals after major cancer surgery are a different group of patients than those readmitted to the index hospital. Accounting for this, we did not find significant differences in short-term clinical outcomes or costs of care based on readmission location; however, differences in long-term outcomes were observed that should be further explored in future studies.

MicroRNA expression in formalin-fixed paraffin-embedded tissue (FFPE) or plasma may add value for cancer management. The GastroGenus miR Panel was developed to measure 55 cancer-specific human microRNAs, Epstein-Barr virus (EBV)-encoded microRNAs, and controls. This Q-rtPCR panel was applied to 100 FFPEs enriched for adenocarcinoma or adjacent non-malignant mucosa, and to plasma of 31 patients. In FFPE, microRNAs upregulated in malignant versus adjacent benign gastric mucosa were hsa-miR-21, -155, -196a, -196b, -185, and -let-7i. Hsa-miR-18a, 34a, 187, -200a, -423-3p, -484, and -744 were downregulated. Plasma of cancer versus non-cancer controls had upregulated hsa-miR-23a, -103, and -221 and downregulated hsa-miR-378, -346, -486-5p, -200b, -196a, -141, and -484. EBV-infected versus uninfected cancers expressed multiple EBV-encoded microRNAs, and concomitant dysregulation of four human microRNAs suggests that viral infection may alter cellular biochemical pathways. Human microRNAs were dysregulated between malignant and benign gastric mucosa and between plasma of cancer patients and non-cancer controls. Strong association of EBV microRNA expression with known EBV status underscores the ability of microRNA technology to reflect disease biology. Expression of viral microRNAs in concert with unique human microRNAs provides novel insights into viral oncogenesis and reinforces the potential for microRNA profiles to aid in classifying gastric cancer subtypes. Pilot studies of plasma suggest the potential for a noninvasive addition to cancer diagnostics.

Confidence should increase during surgical training and practice. However, few data exist regarding confidence of surgeons across this continuum. Confidence may develop differently in clinical and personal domains, or may erode as specialization or age restricts practice. A reliable scale of confidence is needed to track this competency. A novel survey was distributed to surgeons in private and academic settings. One hundred and thirty-four respondents completed this cross-sectional survey. Surgeons reported anticipated reactions to clinical scenarios within three patient care domains (acute inpatient, nonacute inpatient, and outpatient) and in personal spheres. Confidence scores were plotted against years of experience. Curves of best fit were generated and trends assessed. A subgroup completed a second survey after four years to assess the survey's reliability over time. During residency, there is steep improvement in confidence reported by surgeons in all clinical domains, with further increase for inpatient domains during transition into practice. Confidence in personal spheres also increases quickly during residency and thereafter. The surgeon confidence scale captures the expected acquisition of confidence during early surgical experience, and will have value in following trends in surgeon confidence as training and practice patterns change.

Significant morbidity and mortality have historically been reported for surgical resection of gastric and gastroesophageal junction tumors. We evaluated our experience to determine morbidity and mortality and evaluated demographic and pathologic risk factors associated with postoperative outcome and long-term survival. A retrospective, Institutional Review Board-approved, single-institution database identified 102 patients who underwent resection with curative intent for gastroesophageal junction or gastric carcinoma from 2004 to 2012. The method of Kaplan and Meier was used to describe overall survival and estimate median survival. Of 102 patients, 74 were male and 28 were female. Of these, 24 patients were > 70 years of age at surgery (median = 62.9). Forty esophagectomies, 25 total gastrectomies, and 37 subtotal gastrectomies were performed. Two patients died (one esophagectomy and one gastrectomy). Forty-one developed a complication: 17 minor and 35 major, including six anastomotic leaks. Patients with low preoperative albumin (P = 0.01) and increased age (P = 0.05) were associated with having a postoperative complication; extent of nodal dissection (P = 0.48), jejunostomy (0.24), performance status (P = 0.77), type of surgery (P = 0.74), and neoadjuvant therapy (P = 0.24) were not associated. More extensive nodal dissection was associated with a decreased risk of death (P = 0.007). Having any complication (P = 0.20), an anastomotic leak (P = 0.17), worse grade of complication (P = 0.15), presence of feeding jejunostomy tube (P = 0.17), and neoadjuvant therapy (P = 0.30) were not associated with changes in overall survival. Thorough lymph node dissection improves survival without increasing postoperative morbidity. The data advocate for increased lymph node yield and close attention to nutritional support in gastroesophageal carcinoma patients.

Current histopathologic classification schemes for gastric adenocarcinoma have limited clinical utility and are difficult to apply due to tumor heterogeneity. Elucidation of molecular subtypes of gastric cancer may contribute to our understanding of gastric cancer biology and to the development of new molecular markers that may lead to improved diagnosis, therapy, or prognosis. We previously demonstrated that Epstein-Barr virus (EBV)-infected gastric cancers have a distinct human gene expression profile compared with uninfected cancers. We now examine the histopathologic features characterizing infected (n=14) and uninfected (n=89) cancers; the latter of which are now further divided into 2 major molecular subtypes based on expression patterns of 93 RNAs. One uninfected gastric cancer subtype was distinguished by upregulation of 3 genes with neuroendocrine (NE) function (CHGA, GAST, and REG4 encoding chromogranin, gastrin, and the secreted peptide REG4 involved in epithelial cell regeneration), implicating hormonal factors in the pathogenesis of a major class of gastric adenocarcinomas. Evidence of NE differentiation (molecular, immunohistochemical, or morphologic) was mutually exclusive of EBV infection. EBV-infected tumors tended to have solid-type morphology with lymphoid stroma. This study reveals novel molecular subtypes of gastric cancer and their associated morphologies that demonstrate divergent NE features.

Background and Objectives: Tumor mitotic rate (TMR) is an important prognostic variable for patients with thin melanoma. However it remains unclear what the significance of TMR is for more deeply invasive melanoma pathologically staged with a sentinel lymph node biopsy. We sought to determine the prognostic value of TMR in clinically node-negative T2 melanoma patients staged with sentinel lymphadenectomy., Methods: A prospective IRB-approved database of cutaneous melanoma patients treated from 09/01/1997-03/01/2011 was used to identify patients with T2 melanoma staged with a SLN. Associations were evaluated using Fisher's Exact test, and Kaplan-Meier analysis., Results: Three hundred thirteen T2 patients were included. 19% had ulceration, 11% a positive sentinel node (SLN), and 10% recurred. 44% of patients had TMR ≥ 1/mm(2). TMR ≥ 1/mm(2) did not predict SLN status. TMR ≥ 1/mm(2) was significantly associated with recurrence in SLN negative patients; only 3% of those with TMR < 1/mm(2) developed a recurrence compared to 16% of those with TMR ≥ 1/mm(2) (P < 0.0001)., Conclusions: Although TMR ≥ 1/mm(2) is not associated with risk of SLN involvement in T2 melanoma, it is a significant risk factor for recurrence when SLN negative. As such, TMR could be used to stratify follow-up regimens in SLN negative T2 patients., (© 2015 Wiley Periodicals, Inc.)

Purpose: Recurrence risk assessment to make treatment decisions for early-stage colon cancer patients is a major unmet medical need. The aim of this retrospective multicenter study was to evaluate the clinical utility of guanylyl cyclase C (GCC) mRNA levels in lymph nodes on colon cancer recurrence., Methods: The proportion of lymph nodes with GCC-positive mRNA (LNR) was evaluated in 463 untreated T3N0 patients, blinded to clinical outcomes. One site's (n = 97) tissue grossing method precluded appropriate lymph node assessment resulting in post hoc exclusion. Cox regression models tested the relationship between GCC and the primary endpoint of time to recurrence. Assay methods, primary analyses, and cut points were all prespecified., Results: Final dataset contained 366 patients, 38 (10%) of whom had recurrence. Presence of four or more GCC-positive lymph nodes was significantly associated with risk of recurrence [hazard ratio (HR) = 2.46, 95% confidence interval (CI), 1.07-5.69, P = 0.035], whereas binary GCC LNR risk class (HR = 1.87, 95% CI, 0.99-3.54, P = 0.054) and mismatch repair (MMR) status (HR = 0.77, 95% CI, 0.36-1.62, P = 0.49) were not. In a secondary analysis using a 3-level GCC LNR risk group classification of high (LNR > 0.20), intermediate (0.10 < LNR ≤ 0.20), and low (LNR ≤ 0.10), high-risk patients had a 2.5 times higher recurrence risk compared with low-risk patients (HR = 2.53, 95% CI, 1.24-5.17, P = 0.011)., Conclusions: GCC status is a promising prognostic factor independent of traditional histopathology risk factors in a contemporary population of patients with stage IIa colon cancer not treated with adjuvant therapy, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique., (©2014 American Association for Cancer Research.)

Studies of ipilimumab have shown improved overall survival in patients with metastatic cutaneous melanoma. As a result, use of ipilimumab in patients with Stage IV melanoma is rapidly increasing. Patients with Stage IV melanoma often require urgent operations for complications from metastases, but little is known about the safety of surgical intervention for patients receiving ipilimumab. We performed a systematic review of the literature using PubMed. Our search terms were melanoma and ipilimumab. We excluded foreign language articles, review articles, and those not addressing cutaneous melanoma. We identified 194 publications matching the search criteria. Only six of those met the inclusion criteria. In these six publications, seven patients who had undergone surgical intervention during treatment with ipilimumab were described. There were no documented surgical complications. We reviewed our institutional experience and identified an additional three patients. No postoperative complications could be attributed directly to ipilimumab. There are limited data on the safety of surgical intervention during treatment with ipilimumab. Preliminary reports suggest there is no reason to withhold or delay surgery for patients receiving ipilimumab therapy.

Background: Follow-up of patients with sentinel lymph node-positive stage III melanoma uses history, physical exam, and cross-sectional imaging. The aim of this study was to evaluate positron emission tomographic (PET)/computed tomographic (CT) scans in the detection of recurrence., Methods: From 2003 to 2009, a single-institution prospective database of all cutaneous melanoma patients was used to identify sentinel lymph node-positive stage III patients with disease-free survival >1 year and 1 restaging PET/CT scan., Results: Thirty-eight patients were identified, with a median follow-up period of 27.5 months. Seven (18%) developed recurrence (median time to recurrence, 25 months). Recurrences were detected as follows: 3 by patients, 1 by physician, 1 by PET/CT scan and lactate dehydrogenase, 1 by PET/CT scan, and 1 by brain magnetic resonance imaging. One hundred eight follow-up PET/CT scans were performed. Two of 38 patients had asymptomatic metastases detected by routine restaging PET/CT scan, and there were 9 scans with false-positive results., Conclusions: With short follow-up, the utility of routine PET/CT scans in identifying unsuspected recurrence in patients with sentinel lymph node-positive stage III melanoma appears minimal., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer., Methods: All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment., Results: LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy., Conclusion: Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

Background: Local recurrence (LR) rates in patients with retroperitoneal sarcoma (RPS) are high, ranging from 40% to 80%, with no definitive studies describing the best way to administer radiation. Intraoperative electron beam radiation therapy (IOERT) provides a theoretical advantage for access to the tumor bed with reduced toxicity to surrounding structures. The goal of this study was to evaluate the role of IOERT in high-risk patients., Methods: An institutional review board approved, single institution sarcoma database was queried to identify patients who received IOERT for treatment of RPS from 2/2001 to 1/2009. Data were analyzed using the Kaplan-Meier method, Cox regression, and Fisher Exact tests., Results: Eighteen patients (median age 51 y, 25-76 y) underwent tumor resection with IOERT (median dose 1250 cGy) for primary (n = 13) and recurrent (n = 5) RPS. Seventeen patients received neoadjuvant radiotherapy. Eight high-grade and 10 low-grade tumors were identified. Median tumor size was 15 cm. Four patients died and two in the perioperative period. Median follow-up of survivors was 3.6 y. Five patients (31%) developed an LR in the irradiated field. Three patients with primary disease (25%) and two (50%) with recurrent disease developed an LR (P = 0.5). Four patients with high-grade tumors (57%) and one with a low-grade tumor (11%) developed an LR (P = 0.1). The 2- and 5-y OS rates were 100% and 72%. Two- and 5-y LR rates were 13% and 36%., Conclusions: Using a multidisciplinary approach, we have achieved low LR rates in our high-risk patient population indicating that IOERT may play an important role in managing these patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Data indicate that students are unprepared to perform basic medical procedures on graduation. The authors' aim was to characterize graduating students' experience with and opinions about these skills., Method: In 2011, an online survey queried 156 fourth-year medical students about their experience with, and actual and desired levels of competence for, nine procedural skills (Foley catheter insertion, nasogastric tube insertion, venipuncture, intravenous catheter insertion, arterial puncture, basic suturing, endotracheal intubation, lumbar puncture, and thoracentesis). Students self-reported competence on a four-point Likert scale (4=independently performs skill; 1=unable to perform skill). Data were analyzed by analysis of variance and Student t test. A five-point Likert scale was used to assess student confidence., Results: One hundred thirty-four (86%) students responded. Two skills were performed more than two times by over 50% of students: Foley catheter insertion and suturing. Mean level of competence ranged from 3.13±0.75 (Foley catheter insertion) to 1.7±0.7 (thoracentesis). A gap in desired versus actual level of competence existed for all procedures (P<.0001). There was a correlation between the number of times a procedure had been performed and self-reported competence for all skills except arterial puncture and suturing., Conclusions: Participants had performed most skills infrequently and rated themselves as being unable to perform them without assistance. Strategies to improve student experience and competence of procedural skills must evolve to improve the technical competency of graduating students because their current competency varies widely.

Introduction: Professionalism is now recognized as a core competency for graduate medical education and maintenance of certification. However, few models exist in plastic surgery that define, teach, and assess professionalism as a competency. The purpose of this project was to evaluate the effectiveness of a professionalism curriculum in an academic plastic surgery practice., Methods: We created and conducted a 6-wk, 12-h course for health care professionals in plastic surgery (faculty, residents, nurses, medical students). Teaching methods included didactic lectures, journal club, small group discussions, and book review. Topics included: (1) Professionalism in Our Culture, (2) Leadership Styles, (3) Modeling Professional Behavior, (4) Leading Your Team, (5) Managing Oneself, and (6) Leading While You Work. Using Kirkpatrick methodology to assess perception of the course (level 1 data), learning of the material (level 2 data), effect on behavior (level 3 data), and impact on the organization (level 4 data), we compiled participant questionnaires, scores from pre- and post-tests, and such metrics as incidence of sentinel events (defined as infractions requiring involvement by senior administrators), number of patient complaints reported to Patient Relations, and patient satisfaction (Press Ganey surveys), for the 6 mo before and after the course., Results: Thirty health care professionals participated in a 6-wk course, designed to improve professionalism in plastic surgery. Level 1 data: Although only 56.5% of respondents felt that the course was a "good use of my time," 73.9% agreed that the course "will help me become a better professional" and 82.6% "would recommend the course to others." Level 2 data: Post-test scores increased from 48% to 70% (P < 0.05), and the ability to recall all six competencies increased from 22% to 73% (P < 0.01). Level 3 data: The number of sentinel events in our division decreased from 13 to three. After the course, one resident was placed on probation and resigned, and two other employees left the division after being counseled on issues of professionalism. Interestingly, these participants did very well on the post-test but were not considered to be "team players." Level 4 data: Patient complaints decreased from 14 to eight, and patient satisfaction increased from 85.5% to 90.5%., Conclusions: A focused curriculum in professionalism may improve the knowledge of participants and overall behavior of the group, but may not affect individual attitudes. Nevertheless, efforts toward assessing, teaching, and influencing professionalism in plastic surgery are very valuable and should be pursued by educators to help satisfy Graduate Medical Education/Maintenance of Certification requirements and to improve the performance of the organization., (Copyright © 2013. Published by Elsevier Inc.)

Introduction: Few educational programs exist for medical students that address professionalism in surgery, even though this core competency is required for graduate medical education and maintenance of board certification. Lapses in professional behavior occur commonly in surgical disciplines, with a negative effect on the operative team and patient care. Therefore, education regarding professionalism should begin early in the surgeon's formative process, to improve behavior. The goal of this project was to enhance the attitudes and knowledge of medical students regarding professionalism, to help them understand the role of professionalism in a surgical practice., Methods: We implemented a 4-h seminar, spread out as 1-h sessions over the course of their month-long rotation, for 4th-year medical students serving as acting interns (AIs) in General Surgery, a surgical subspecialty, Obstetrics/Gynecology, or Anesthesia. Teaching methods included lecture, small group discussion, case studies, and journal club. Topics included Cognitive/Ethical Basis of Professionalism, Behavioral/Social Components of Professionalism, Managing Yourself, and Leading While You Work. We assessed attitudes about professionalism with a pre-course survey and tracked effect on learning and behavior with a post-course questionnaire. We asked AIs to rate the egregiousness of 30 scenarios involving potential lapses in professionalism., Results: A total of 104 AIs (mean age, 26.5 y; male to female ratio, 1.6:1) participated in our course on professionalism in surgery. Up to 17.8% of the AIs had an alternate career before coming to medical school. Distribution of intended careers was: General Surgery, 27.4%; surgical subspecialties, 46.6%; Obstetrics/Gynecology, 13.7%; and Anesthesia, 12.3%. Acting interns ranked professionalism as the third most important of the six core competencies, after clinical skills and medical knowledge, but only slightly ahead of communication. Most AIs believed that professionalism could be taught and learned, and that the largest obstacle was not enough time in the curriculum. The most effective reported teaching methods were mentoring and modeling; lecture and journal club were the effective. Regarding attitudes toward professionalism, the most egregious examples of misconduct were substance abuse, illegal billing, boundary issues, sexual harassment, and lying about patient data, whereas the least egregious examples were receiving textbooks or honoraria from drug companies, advertising, self-prescribing for family members, and exceeding work-hour restrictions. The most important attributes of the professional were integrity and honesty, whereas the least valued were autonomy and altruism. The AIs reported that the course significantly improved their ability to define professionalism, identify attributes of the professional, understand the importance of professionalism, and integrate these concepts into practice (all P < 0.01)., Conclusions: Although medical students interested in surgery may already have well-formed attitudes and sophisticated knowledge about professionalism, this core competency can still be taught to and learned by trainees pursuing a surgical career., (Copyright © 2012. Published by Elsevier Inc.)

Introduction: Learning procedural skills as a medical student has evolved, as task trainers and simulators are now ubiquitous. It is yet unclear whether they have supplanted bedside teaching or are adjuncts to it, and whether faculty or residents are responsible for student skills education in this era. In this study we sought to characterize the experience and opinions of both medical students and faculty on procedural skills training., Methods: Surveys were sent to clinical medical students and faculty at UNC Chapel Hill. Opinions on the ideal learning environment for basic procedural skills, as well as who serves as primary teacher, were gathered using a 4-point Likert scale. Responses were compared via Fisher exact test., Results: A total of 237 students and 279 faculty responded. Third-year students were more likely to report simulation as the primary method of education (64%), compared to either fourth-year students (35%; P < 0.0001) or faculty (43%; P = 0.0018). Third- and fourth-year students were also more likely to report interns as a primary teacher (15% and 10%, respectively) as opposed to faculty (2%), and less likely to suggest faculty were the primary teacher (30% and 21%, respectively, versus 35%), P < 0.0001. Residents were the primary teachers for all three groups (55%, 70%, and 63% respectively)., Conclusions: Our data suggest that both medical students and faculty recognize the utility of simulation in procedural skills training, but vary in the degree to which they think simulation is or should be the primary instructional tool. Both groups suggest residents are the primary teacher of these skills., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Melanoma excisions frequently are associated with significant soft-tissue defects, creating the need for complex closures. These closures could be performed by either surgical oncologists or plastic surgeons. We sought to quantify the relative value units (RVUs) and describe the practice patterns of 2 academic surgical subspecialties after a melanoma excision., Methods: After institutional review board approval, a retrospective data analysis of a billing database was conducted on all melanoma patients undergoing an excision and closure by surgical oncology and plastic surgery departments in 2007. Data were obtained using billing records for Current Procedural Terminology diagnosis codes. RVUs were used to quantify the value added to each practice from these closures. The surgical oncologist and patient decided if a plastic surgeon was needed., Results: A total of 270 closures were performed, 53 (19.9%) primary and 217 (80.1%) complex. The surgical oncologists performed most complex closures (188; 86.6%), and the plastic surgeons performed the remainder (29; 13.4%), generating a total of 1,921 RVUs (1,630 by the surgical oncologists and 291 by the plastic surgeons). For analysis, complex closures were divided among 4 anatomic sites: trunk, upper extremity, lower extremity, and head and neck. Most closures by the surgical oncologists were adjacent tissue rearrangements (155; 82%) and the remainder were skin grafts (33; 18%). Closures by the plastic surgeons were more likely to be a full-thickness skin graft (P < .0027) in the head and neck region (P < .0001), with a higher associated median RVU/case (10.15 compared with 8.44 for the surgical oncologists; P < .0002)., Conclusions: At our institution, the majority of melanoma closures were performed by surgical oncologists. However, plastic surgery often was involved in more complex closures in the head and neck. This data set quantifies the RVUs added and describes the types of closures performed in an academic melanoma practice., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: EBV DNA is found within the malignant cells of 10% of gastric cancers. Modern molecular technology facilitates identification of virus-related biochemical effects that could assist in early diagnosis and disease management., Methods: In this study, RNA expression profiling was performed on 326 macrodissected paraffin-embedded tissues including 204 cancers and, when available, adjacent non-malignant mucosa. Nanostring nCounter probes targeted 96 RNAs (20 viral, 73 human, and 3 spiked RNAs)., Results: In 182 tissues with adequate housekeeper RNAs, distinct profiles were found in infected versus uninfected cancers, and in malignant versus adjacent benign mucosa. EBV-infected gastric cancers expressed nearly all of the 18 latent and lytic EBV RNAs in the test panel. Levels of EBER1 and EBER2 RNA were highest and were proportional to the quantity of EBV genomes as measured by Q-PCR. Among protein coding EBV RNAs, EBNA1 from the Q promoter and BRLF1 were highly expressed while EBNA2 levels were low positive in only 6/14 infected cancers. Concomitant upregulation of cellular factors implies that virus is not an innocent bystander but rather is linked to NFKB signaling (FCER2, TRAF1) and immune response (TNFSF9, CXCL11, IFITM1, FCRL3, MS4A1 and PLUNC), with PPARG expression implicating altered cellular metabolism. Compared to adjacent non-malignant mucosa, gastric cancers consistently expressed INHBA, SPP1, THY1, SERPINH1, CXCL1, FSCN1, PTGS2 (COX2), BBC3, ICAM1, TNFSF9, SULF1, SLC2A1, TYMS, three collagens, the cell proliferation markers MYC and PCNA, and EBV BLLF1 while they lacked CDH1 (E-cadherin), CLDN18, PTEN, SDC1 (CD138), GAST (gastrin) and its downstream effector CHGA (chromogranin). Compared to lymphoepithelioma-like carcinoma of the uterine cervix, gastric cancers expressed CLDN18, EPCAM, REG4, BBC3, OLFM4, PPARG, and CDH17 while they had diminished levels of IFITM1 and HIF1A. The druggable targets ERBB2 (Her2), MET, and the HIF pathway, as well as several other potential pharmacogenetic indicators (including EBV infection itself, as well as SPARC, TYMS, FCGR2B and REG4) were identified in some tumor specimens., Conclusion: This study shows how modern molecular technology applied to archival fixed tissues yields novel insights into viral oncogenesis that could be useful in managing affected patients.