Tumor-intrinsic and Cancer-associated Fibroblast Subtypes Independently Predict Outcomes in Pancreatic Cancer.

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. 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 (SSCs) were used to determine classical and basal-like subtypes as well as tumor-permissive permCAF and tumor-restraining restCAF subtypes. Survival was analyzed using log-rank test. RESULTS: Patients who received NAT had an increase in overall survival (OS), with median survival of 27.9 months compared to 20.1 months for those who did not receive NAT, but the difference did not reach statistical significance (HR 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 subtype had the best outcomes. When evaluated together, patients with classical-restCAF subtype had the best OS and basal-permCAF the worst OS (P<0.0001). NAT patients with classical-restCAF subtype demonstrated the longest OS compared to 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.

Lymph node metastases in young patients with gastrointestinal stromal tumor: A nationwide analysis.

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.

Use and Costs of Sentinel Lymph Node Biopsy in Non-Ulcerated T1b Melanoma: Analysis of a Population-Based Registry.

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 mm2, 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.

Direct Comparison of In-Person Versus Virtual Interviews for Complex General Surgical Oncology Fellowship in the COVID-19 Era.

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.

Allyship in Surgical Residents: Evidence for LGBTQ Competency Training in Surgical Education.

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.

Socioeconomic factors in timing of esophagectomy and association with outcomes.

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.

Impact of Location of Readmission on Outcomes After Major Cancer Surgery.

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.

Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns.

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.

Prognostic significance of tumor mitotic rate in T2 melanoma staged with sentinel lymphadenectomy.

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.

Clinical and Histological Response to Talimogene Laherparepvec Therapy in Advanced Melanoma: Impact on Overall Survival.

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.

Sometimes you can't make it on your own: the impact of a professionalism curriculum on the attitudes, knowledge, and behaviors of an academic plastic surgery practice.

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.

Intraoperative electron radiation therapy as an important treatment modality in retroperitoneal sarcoma.

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.

Self-compassion training to improve well-being for surgical residents.

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.

Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III/IV melanoma.

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 SUVmax of the hottest tumor lesion per patient revealed that the 'low' C11-AMT SUVmax was associated with longer progression-free survival in our clinical trial (n = 26). We saw no such trends with pretreatment FDG PET SUVmax. 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.

Systemic Therapy for Melanoma: ASCO Guideline Update.

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.

Who teaches basic procedural skills: student experience versus faculty opinion.

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.

Get on your boots: preparing fourth-year medical students for a career in surgery, using a focused curriculum to teach the competency of professionalism.

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.

Impact of breast cancer molecular subtypes on locoregional recurrence in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer.

BACKGROUND: Gene expression studies have identified distinct breast cancer subtypes, including luminal A, luminal B, Her2-enriched, and Basal-like, which differ in survival. The impact of subtypes on locoregional recurrence (LRR) after neoadjuvant chemotherapy for locally advanced breast cancer is unknown. METHODS: A total of 149 patients with stage II and III breast cancer with known ER, PR, and HER2 who underwent neoadjuvant chemotherapy from 1991 to 2005 were analyzed. We used clinical assays to distinguish luminal A (ER or PR+/HER2-, n = 55), luminal B (ER or PR+/HER2+, n = 25), HER2 (ER and PR-/HER2+, n = 20), and Basal-like (ER, PR, and HER2-, n = 49) subtypes. Covariates associated with LRR were evaluated by logistic regression and differences between subtypes tested using Wald χ(2). RESULTS: Median follow-up was 55 months. Forty-nine (33%) patients had breast conservation (BCT) with radiation, 82 (55%) had a mastectomy with radiation, and 18 (12%) had a mastectomy alone. Eighty-eight (59%) were clinically node positive. A pathologic complete response was seen in 39 (26%) patients. LRR was identified in 11 (7%) patients: 2 after BCT (4%) and 9 after mastectomy (9%). LRR rates by subtype are as follows: luminal A 2 of 55 (4%), luminal B 1 of 25 (4%), Her2 1 of 20 (5%), and basal-like 7 of 49 (14%). Compared with all other subtypes, basal-like patients were more likely to have a LRR (7/49 (14%) vs. 4/100 (4%), p = 0.03). CONCLUSIONS: Molecular subtype predicts LRR with basal-like patients more likely to develop LRR. These patients may be candidates for investigation with novel chemotherapy regimens and radiation sensitizing agents, which may offer improvement in local control.

Evaluation of guanylyl cyclase C lymph node status for colon cancer staging and prognosis.

PURPOSE: The prognostic significance of guanylyl cyclase C (GCC) gene expression in lymph nodes (LNs) was evaluated in patients with stage II colon cancer who were not treated with adjuvant chemotherapy. We report a planned analysis performed on 241 patients. METHODS: GCC mRNA was quantified by RT-qPCR using formalin-fixed LN tissues from patients with untreated stage II colon cancer who were diagnosed from 1999-2006 with at least ten LNs examined and blinded to clinical outcomes. Lymph node ratio (LNR) is the number of GCC-positive nodes divided by total number of informative LNs. Risk categories of low (0-0.1) and high (>0.1) for LNR were chosen by significance using Cox regression models. The data were tested for association with time to recurrence. RESULTS: Twenty-nine patients (12%) had a disease recurrence or cancer death. The LNR significantly predicted higher recurrence risk for 84 patients (34.9%) classified as high risk (hazard ratio (HR), 2.38; P=0.02). The estimated 5-year recurrence rates were 10% and 27% for the low- and high-risk groups, respectively. After adjusting for age, T stage, number of nodes assessed, and MMR status, a significant association remained (HR, 2.61; P=0.02). In a subset of patients (n=181) with T3 tumor, ≥12 nodes examined and negative margins, a significant association between the GCC LNR and recurrence risk also was observed (HR, 5.06; P=0.003). CONCLUSIONS: Our preliminary results suggest that detection of GCC mRNA in LNs is associated with risk of disease recurrence in patients with untreated stage II colon cancer. A larger validation study is ongoing.