Prospective, randomized, double-blind phase 2B trial of the TLPO and TLPLDC vaccines to prevent recurrence of resected stage III/IV melanoma: a prespecified 36-month analysis.

BACKGROUND: The tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is made by ex vivo priming matured autologous dendritic cells (DCs) with yeast cell wall particles (YCWPs) loaded with autologous tumor lysate (TL). The tumor lysate, particle only (TLPO) vaccine uses autologous TL-loaded YCWPs coated with silicate for in vivo DC loading. Here we report the 36-month prespecified analyses of this prospective, randomized, double-blind trial investigating the ability of the TLPO and TLPLDC (±granulocyte-colony stimulating factor (G-CSF)) vaccines to prevent melanoma recurrence in high-risk patients. METHODS: Patients with clinically disease-free stage III/IV melanoma were randomized 2:1 initially to TLPLDC versus placebo (n=124) and subsequently TLPO versus TLPLDC (n=63). All patients were randomized and blinded; however, the placebo control arm was replaced in the second randomization scheme with another novel vaccine; some analyses in this paper therefore reflect a combination of the two randomization schemes. Patients receiving the TLPLDC vaccine were further divided by their method of DC harvest (with or without G-CSF pretreatment); this was not randomized. The use of standard of care checkpoint inhibitors was not stratified between groups. Safety was assessed and Kaplan-Meier and log-rank analyses compared disease-free (DFS) and overall survival (OS). RESULTS: After combining the two randomization processes, a total of 187 patients were allocated between treatment arms: placebo (n=41), TLPLDC (n=103), or TLPO (n=43). The allocation among arms created by the addition of patients from the two separate randomization schemes does not reflect concurrent randomization among all treatment arms. TLPLDC was further divided by use of G-CSF in DC harvest: no G-CSF (TLPLDC) (n=47) and with G-CSF (TLPLDC+G) (n=56). Median follow-up was 35.8 months. Only two patients experienced a related adverse event ≥grade 3, one each in the TLPLDC+G and placebo arms. DFS was 27.2% (placebo), 55.4% (TLPLDC), 22.9% (TLPLDC+G), and 60.9% (TLPO) (p<0.001). OS was 62.5% (placebo), 93.6% (TLPLDC), 57.7% (TLPLDC+G), and 94.6% (TLPO) (p=0.002). CONCLUSIONS: The TLPO and TLPLDC (without G-CSF) vaccines were associated with improved DFS and OS in this clinical trial. Given production and manufacturing advantages, the efficacy of the TLPO vaccine will be confirmed in a phase 3 trial. TRIAL REGISTRATION NUMBER: NCT02301611.

Divergent clinical outcomes in a phase 2B trial of the TLPLDC vaccine in preventing melanoma recurrence and the impact of dendritic cell collection methodology: a randomized clinical trial.

BACKGROUND: A randomized, double-blind, placebo-controlled phase 2b trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine was conducted in patients with resected stage III/IV melanoma. Dendritic cells (DCs) were harvested with and without granulocyte-colony stimulating factor (G-CSF). This analysis investigates differences in clinical outcomes and RNA gene expression between DC harvest methods. METHODS: The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles (YCWPs) and exposing them to phagocytosis by DCs. For DC harvest, patients had a direct blood draw or were pretreated with G-CSF before blood draw. Patients were randomized 2:1 to receive TLPLDC or placebo. Differences in disease-free survival (DFS) and overall survival (OS) were evaluated. RNA-seq analysis was performed on the total RNA of TLPLDC + G and TLPLDC vaccines to compare gene expression between groups. RESULTS: 144 patients were randomized: 103 TLPLDC (47 TLPLDC/56 TLPLDC + G) and 41 placebo (19 placebo/22 placebo + G). Median follow-up was 27.0 months. Both 36-month DFS (55.8% vs. 24.4% vs. 30.0%, p = 0.010) and OS (94.2% vs. 69.8% vs. 70.9%, p = 0.024) were improved in TLPLDC compared to TLPLDC + G or placebo, respectively. When compared to TLPLDC + G vaccine, RNA-seq from TLPLDC vaccine showed upregulation of genes associated with DC maturation and downregulation of genes associated with DC suppression or immaturity. CONCLUSIONS: Patients receiving TLPLDC vaccine without G-CSF had improved OS and DFS. Outcomes remained similar between patients receiving TLPLDC + G and placebo. Direct DC harvest without G-CSF had higher expression of genes linked to DC maturation, likely improving clinical efficacy.

General Surgery Residency Virtual Recruitment During the Pandemic: An Analysis of Applicant Surveys.

INTRODUCTION: The COVID-19 pandemic forced a sudden change from in-person to virtual interviews for the general surgery residency match. General surgery programs and applicants adopted multiple strategies to best mimic in-person recruitment. The purpose of this study was to evaluate applicant opinions of the virtual recruitment format. MATERIALS AND METHODS: Postinterview survey responses for applicants interviewing at a single general surgery residency program in the 2020-2021 and 2021-2022 cycles were evaluated. All interviewed applicants were sent an anonymous survey assessing the virtual interview structure, their impression of the program, and their opinions on recruitment in the future. RESULTS: The response rate was 31.2% (n = 60). Most (88.4%) respondents reported a more favorable view of the program after a virtual interview. Factors that were most likely to create a favorable impression were residents (89.6%) and culture (81.0%). 50.8% of applicants favored virtual-only interviews. The majority of applicants (60.3%), however, preferred the virtual interview remain a component of the application process, 34.4% recommended that virtual interviews be used as an initial screen before in-person invites, while 19.0% suggested applicants should interview in-person or virtually without penalty. 62.1% favored capping the number of interviews offered by programs and accepted by applicants. CONCLUSIONS: The virtual interview format for general surgery residency allows applicants to effectively evaluate a residency program. Applicants are in favor of a combination of virtual and in-person interviews in the future. Innovation in the recruitment process, including limiting the number of applications and incorporating virtual events, is supported by applicants.

Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study.

BACKGROUND: Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs). RESULTS: Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN - and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25-6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan-Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p < 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72-14.40, p < 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54-8.80, p < 0.01). CONCLUSIONS: In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.

How Informed Is Your Informed Consent: Evaluating Differences Between Resident and Attending Obtained Consents for Cholecystectomy.

OBJECTIVE: There is considerable variability in surgeons' approach to write and obtain informed consent for surgery, particularly among resident trainees. We analyzed differences in procedures and complications described in documented surgical consents for cholecystectomy between residents and attendings. We hypothesized that attending consents would describe more comprehensive procedures and complications than those done by residents. DESIGN: This is a retrospective analysis of 334 patients who underwent cholecystectomy. Charts were queried for demographics, surgical approach, whether the consent was completed electronically, and which provider completed the consent. Specifically, consents were evaluated for inclusion of possible conversion to open procedure, intraoperative cholangiogram, bile duct injury, injury to nearby structures, reoperation, bile leak, as well as if the consent matched the actual procedure performed. SETTING: This study was conducted at an accredited general surgery training program at an academic tertiary care center in the Midwest. PARTICIPANTS: This was a review of 334 patients who underwent cholecystectomy over a 1 year period. RESULTS: Of all documented consents analyzed, 153 (47%) specifically included possible intraoperative cholangiogram, 156 (47%) included bile duct injury, 76 (23%) included injury to nearby structures, 22 (7%) included reoperation, and 62 (19%) included bile leak. In comparing residents and attendings, residents were more likely to consent for bile duct injury (p = 0.002), possible intraoperative cholangiogram (p = 0.0007), injury to nearby structures (p < 0.0001), reoperation (p < 0.0001), and bile leak (p < 0.0001). CONCLUSIONS: Significant variation exists between documentation between resident and attending cholecystectomy consents, with residents including more complications than attendings on their consent forms. These data suggest that experience alone does not predict content of written consents, particularly for common ambulatory procedures. Education regarding the purpose of informed consent and what should be included in one may lead to a reduction in variability between providers.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Summary of Key Clinical Trials.

The peritoneal cavity is a common site of metastatic spread from colorectal cancer (CRC). Patients with peritoneal metastases (PM) often have aggressive underlying tumor biology and poor survival. While only a minority of patients with CRC have potentially resectable disease, the high overall incidence of CRC makes management of PM a common clinical problem. In this population, cytoreductive surgery (CRS)-hyperthermic intraperitoneal chemotherapy (HIPEC) is the only effective therapy for appropriately selected patients. In this narrative review, we summarize the existing literature on CRS-HIPEC in colorectal PM. Recent prospective clinical trials have shown conflicting evidence regarding the benefit of HIPEC perfusion in addition to CRS. Current strategies to prevent PM in those at high-risk have been shown to be ineffective. Herein we will provide a framework for clinicians to understand and apply these data to treat this complex disease presentation.

Frequency and Characteristics of Social Media Use among General Surgery Trainees.

INTRODUCTION: With increased social isolation due to COVID-19, social media has been increasingly adopted for communication, education, and entertainment. We sought to understand the frequency and characteristics of social media usage among general surgery trainees. MATERIALS AND METHODS: General surgery trainees in 15 American training programs were invited to participate in an anonymous electronic survey. The survey included questions about demographics, frequency of social media usage, and perceptions of risks and benefits of social media. Univariate analysis was performed to identify differences between high users of social media (4-7 h per week on at least one platform) and low users (0-3 h or less on all platforms). RESULTS: One hundred fifty-seven of 591 (26.6%) trainees completed the survey. Most respondents were PGY3 or lower (75%) and high users of social media (74.5%). Among high users, the most popular platforms were Instagram (85.7%), YouTube (85.1%), and Facebook (83.6%). YouTube and Twitter were popular for surgical education (77.3% and 68.2%, respectively). The most reported benefits of social media were improving patient education and professional networking (85.0%), where high users agreed more strongly about these benefits (P = 0.002). The most reported risks were seeing other residents (42%) or attendings (17%) with unprofessional behavior. High users disagreed more strongly about risks, including observing attendings with unprofessional behavior (P = 0.028). CONCLUSIONS: Most respondents were high users of social media, particularly Instagram, YouTube, and Facebook. High users incorporated social media into their surgical education while perceiving more benefits and fewer risks of social media.

Examining the impact of COVID-19 restrictions on the operative volumes of US general surgery residents.

BACKGROUND: In March 2020, the COVID-19 virus global pandemic forced healthcare systems to institute regulations including the cancellation of elective surgical cases, which likely decreased resident operative experience. The objective of this study was to determine whether the COVID-19 pandemic affected operative experiences of US general surgery residents. METHODS: The operative experience of general surgery residents was examined nationally and locally. Aggregate Accreditation Council for Graduate Medical Education (ACGME) case logs for 2018 to 2019 (pre-COVID) and 2019 to 2020 (COVID) graduates were compared using national mean cumulative operative volume for total major and surgeon chief cases. Locally, ACGME case logs were used to analyze the operative experience among residents at a single, academic center. Average operative volumes per month per resident during peak COVID-19 quarantine months were compared with those the previous year. RESULTS: Compared with 2019 graduates, 2020 graduates completed 1.5% fewer total major cases (1055 ± 155 vs 1071 ± 150, P = .011). This was most evident during chief year, with 8.4% fewer surgeon chief cases logged in 2020 compared with 2019 (264 ± 67 vs 289 ± 69, P < .001). Institutional data revealed that during the peak of the pandemic, residents across all levels completed 42.5% fewer total major operations (12 ± 11 vs 20 ± 14, P < .001). This effect was more pronounced among junior residents compared with senior and chief residents. CONCLUSION: The COVID-19 pandemic was associated with decreased resident case volume. The ramifications of the COVID-19 pandemic for operative competency and autonomy should be carefully examined.

Safety and efficacy of autologous tumor lysate particle-loaded dendritic cell vaccination in combination with systemic therapies in patients with recurrent and metastatic melanoma.

Immunotherapy has revolutionized the treatment of melanoma, yet survival remains poor for patients with metastatic disease. The autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine has been shown to be safe adjuvant therapy for patients with resected stage III/IV melanoma who complete the primary vaccine series. Here, we describe an open-label trial of patients with metastatic melanoma treated with TLPLDC vaccine in addition to standard of care (SoC) therapies. The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles, which are phagocytosed by autologous dendritic cells ex vivo. Patients who recurred while enrolled in a phase IIb trial of adjuvant TLPLDC vaccine (crossover cohort) and patients with measurable metastatic melanoma cohort were offered TLPLDC vaccine along with SoC therapies. Tumor response was measured by RECIST 1.1 criteria. Overall survival (OS) and progression-free survival (PFS) were estimated by intention-to-treat analysis. Fifty-four patients were enrolled (28 in crossover cohort; 26 in metastatic melanoma cohort). The vaccine was well-tolerated with no grade ≥3 adverse events when given with SoC therapies to include checkpoint inhibitors, BRAF/MEK inhibitors, tyrosine kinase inhibitors, intralesional therapy and/or radiation. In the crossover arm, OS was 76.5% and PFS was 57.1% (median follow-up of 13.9 months). In the metastatic melanoma arm, OS was 85.7% and PFS was 52.2% (median follow-up 8.5 months). The TLPLDC vaccine is well-tolerated and safe in combination with SoC therapies. Future trials will determine the efficacy of TLPLDC in combination with SoC therapies in metastatic melanoma.

Long-Term Outcomes in a Multicenter, Prospective Cohort Evaluating the Prognostic 31-Gene Expression Profile for Cutaneous Melanoma.

PURPOSE: Current guidelines for postoperative management of patients with stage I-IIA cutaneous melanoma (CM) do not recommend routine cross-sectional imaging, yet many of these patients develop metastases. Methods that complement American Joint Committee on Cancer (AJCC) staging are needed to improve identification and treatment of these patients. A 31-gene expression profile (31-GEP) test predicts metastatic risk as low (class 1) or high (class 2). Prospective analysis of CM outcomes was performed to test the hypotheses that the 31-GEP provides prognostic value for patients with stage I-III CM, and that patients with stage I-IIA melanoma and class 2 31-GEP results have metastatic risk similar to patients for whom surveillance is recommended. MATERIALS AND METHODS: Two multicenter registry studies, INTEGRATE (ClinicalTrials.gov identifier:NCT02355574) and EXPAND (ClinicalTrials.gov identifier:NCT02355587), were initiated under institutional review board approval, and 323 patients with stage I-III CM and median follow-up time of 3.2 years met inclusion criteria. Primary end points were 3-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: The 31-GEP was significant for RFS, DMFS, and OS in a univariate analysis and was a significant, independent predictor of RFS, DMFS, and OS in a multivariable analysis. GEP class 2 results were significantly associated with lower 3-year RFS, DMFS, and OS in all patients and those with stage I-IIA disease. Patients with stage I-IIA CM and a class 2 result had recurrence, distant metastasis, and death rates similar to patients with stage IIB-III CM. Combining 31-GEP results and AJCC staging enhanced sensitivity over each approach alone. CONCLUSION: These data provide a rationale for using the 31-GEP along with AJCC staging, and suggest that patients with stage I-IIA CM and a class 2 31-GEP signature may be candidates for more intense follow-up.

Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis.

BACKGROUND: Checkpoint inhibitors (CPI) in combination with cell-based vaccines may produce synergistic antitumor immunity. The primary analysis of the randomized and blinded phase IIb trial in resected stage III/IV melanoma demonstrated TLPLDC is safe and improved 24-month disease-free survival (DFS) in the per treatment (PT) analysis. Here, we examine efficacy within pre-specified and exploratory subgroups. METHODS: Stage III/IV patients rendered disease-free by surgery were randomized 2:1 to TLPLDC vaccine versus placebo. The pre-specified PT analysis included only patients completing the primary vaccine/placebo series at 6 months. Kaplan-Meier analysis was used to compare 24-month DFS among subgroups. RESULTS: There were no clinicopathologic differences between subgroups except stage IV patients were more likely to receive CPI. In stage IV patients, 24-month DFS was 43% for vaccine versus 0% for placebo (p = 0.098) in the ITT analysis and 73% versus 0% (p = 0.002) in the PT analysis. There was no significant difference in 24-month DFS when stratified by use of immunotherapy or CPI. For patients with resected recurrent disease, 24-month DFS was 88.9% versus 33.3% (p = 0.013) in the PT analysis. All benefit from vaccination was in the PT analysis; no benefit was found in patients receiving up to three doses. CONCLUSION: The TLPLDC vaccine improved DFS in patients completing the primary vaccine series, particularly in the resected stage IV patients. The efficacy of the TLPLDC vaccine will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI versus Placebo + CPI in resected stage IV melanoma patients.

A Phase IIb Randomized Controlled Trial of the TLPLDC Vaccine as Adjuvant Therapy After Surgical Resection of Stage III/IV Melanoma: A Primary Analysis.

BACKGROUND: Melanoma therapy has changed dramatically over the last decade with improvements in immunotherapy, yet many patients do not respond to current therapies. This novel vaccine strategy may prime a patient's immune system against their tumor and work synergistically with immunotherapy against advanced-stage melanoma. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine administered to prevent recurrence in patients with resected stage III/IV melanoma. Patients were enrolled and randomized 2:1 to the TLPLDC vaccine or placebo (empty yeast cell wall particles and autologous dendritic cells). Both intention-to-treat (ITT) and per treatment (PT) analyses were predefined, with PT analysis including patients who remained disease-free through the primary vaccine/placebo series (6 months). RESULTS: A total of 144 patients were randomized (103 vaccine, 41 control). Therapy was well-tolerated with similar toxicity between treatment arms; one patient in each group experienced related serious adverse events. While disease-free survival (DFS) was not different between groups in ITT analysis, in PT analysis the vaccine group showed improved 24-month DFS (62.9% vs. 34.8%, p = 0.041). CONCLUSIONS: This phase IIb trial of TLPLDC vaccine administered to patients with resected stage III/IV melanoma shows TLPLDC is well-tolerated and improves DFS in patients who complete the primary vaccine series. This suggests patients who do not recur early benefit from TLPLDC in preventing future recurrence from melanoma. A phase III trial of TLPLDC + checkpoint inhibitor versus checkpoint inhibitor alone in patients with advanced, surgically resected melanoma is under development. TRIAL REGISTRATION: NCT02301611.

Acquisition and retention of surgical skills taught during intern surgical boot camp.

BACKGROUND: Surgical residencies have implemented boot-camps for early acquisition of basic technical skills for interns. However, educators worry that retention is poor. We hypothesized that a structured boot-camp curriculum would improve skills. METHODS: Interns underwent eight boot-camp sessions at the beginning of residency. Interns completed pre-, post-boot-camp, and end-of-year skills assessments, as well as post-boot camp and end-of-year porcine procedure labs. Proficiency was measured on a 5-point scale and by completion time. RESULTS: After boot-camp, interns improved all domains of knot-tying. Median time decreased for skin-closure (8.3 vs 9.9 min, p < 0.01), peg transfer (57 vs 87 s, p < 0.01), intracorporeal (178 vs 300 s, p < 0.01), and extracorporeal knot-tying (140 vs 259 s, p < 0.01). At the end-of-year assessment, interns exhibited retention of all skills and improved in knot-tying and central line skills. During the retention porcine lab, interns progressed basic but not complex skills. CONCLUSIONS: An eight-week boot-camp effectively improved technical skills among surgery interns. Interns retained all skills and improved upon techniques frequently practiced during intern year.

Swipe right for surgical residency: Exploring the unconscious bias in resident selection.

BACKGROUND: Applicants provide a photo with their application through the Electronic Residency Application Service, which may introduce appearance-based bias. We evaluated whether an unconscious appearance bias exists in surgical resident selection. METHODS: After the match, applicant data from the 2018 to 2019 and 2019 to 2020 application cycles were examined. Reviewers were not provided the applicant photo or self-identified race during the second cycle. Photos provided by candidates were then rated by 4 surgical subspecialty residents who had no prior exposure to applications or interview status. Photos were rated on perceived fitness level, visual appearance, and photo professionalism. An overall photo score was then calculated. RESULTS: In the study, 422 applications were reviewed and 164 received interview invitations during the 2018 to 2019 cycle. Alpha Omega Alpha membership (odds ratio, 2.31; 95% confidence interval, 1.18-4.51), overall photo score (odds ratio, 2.29, 95% confidence interval, 1.43-3.66), research (odds ratio, 5.61, 95% confidence interval, 2.84-11.20), age (odds ratio, 0.86, 95% confidence interval, 0.76-0.99), and step 2 (odds ratio, 1.06, 95% confidence interval, 1.03-1.09) were predictors for receiving an interview. For the 2019 to 2020 cycle, 398 applications were reviewed, and 75 applicants received an invitation. Step 2 (odds ratio, 1.07, 95% confidence interval, 1.02-1.12), research (odds ratio, 2.78, 95% confidence interval, 1.40-5.55), age (odds ratio, 0.82, 95% confidence interval, 0.71-0.95), and overall photo score (odds ratio, 2.27; 95% confidence interval, 1.14-4.52) remained predictors despite reviewers being blinded to the photo during this cycle. CONCLUSION: Although objective metrics remain critical in determining interview invitations, overall perceived applicant appearance may influence the selection process. Although visual appearance was associated with receiving an interview, the Electronic Residency Application Service photo does not ultimately affect selection. This may suggest that appearance may influence other objective and subjective aspects of the application.

Small Bowel Adenocarcinomas: Impact of Location on Survival.

BACKGROUND: Proximal (duodenal) small bowel adenocarcinomas have a worse prognosis than distal (jejuno-ileal) tumors, but differences in patient, tumor, and treatment factors between locations remain unclear. METHODS: Patients in the National Cancer Database with surgically resected pathologic stage I-IV small bowel adenocarcinomas between 2004 and 2015 were analyzed. Clinical stage IV patients were excluded. RESULTS: Proximal tumors (n = 3767) were more likely to be higher grade (OR 1.52, CI 1.22-1.85 for moderately; OR 1.83, CI 1.49-2.33 for poorly differentiated, P < 0.01 for both) and have positive lymph nodes (OR 2.04, CI 1.30-3.23, P < 0.01), while distal tumors (n = 3252) were likely to be larger (OR 1.31, CI 1.07-1.60 for size > 5 cm, P < 0.01). Proximal tumors were associated with worse overall survival (OS) and stage-specific survival compared with distal tumors (all P < 0.01). Cox regression analysis of the entire cohort showed worse survival with community versus academic cancer programs, higher comorbidity scores, pathologic stage IV, poorly differentiated histology, positive nodal or margin status, and proximal location, while female gender, larger tumor size, and chemotherapy predicted better survival. On separate Cox regression analyses of each location, neoadjuvant chemotherapy was associated with better OS in the proximal cohort (HR 0.70, CI 0.55-0.88, P < 0.01), while adjuvant chemotherapy was associated with better OS for both proximal (HR 0.49, CI 0.42-0.57, P < 0.01) and distal tumors (HR 0.68, CI 0.57-0.81, P < 0.01). CONCLUSIONS: Proximal small bowel adenocarcinomas are associated with worse overall and stage-specific survival. This may be due to tumor biologic differences as proximal tumors were more likely to have higher grade. Future studies should further investigate differences between proximal and distal tumors to guide targeted treatment algorithms.

What is the Optimal Preoperative Imaging Modality for Assessing Peritoneal Cancer Index? An Analysis From the United States HIPEC Collaborative.

BACKGROUND: Radiographic prediction of peritoneal carcinomatosis index (PCI) can improve patient selection for cytoreductive surgery. We aimed to determine the correlation of computed tomography (CT)-predicted PCI (CT-PCI) and magnetic resonance imaging (MRI)-predicted PCI (MRI-PCI) with intraoperative-PCI, and if a preoperative-PCI cutoff is associated with incomplete cytoreduction. PATIENTS AND METHODS: Patients from the US HIPEC Collaborative (2000-2017) with appendiceal, colorectal, or peritoneal mesothelioma (PM) histology who underwent cytoreductive surgery were included. Pearson correlation coefficients were used to determine correlation between preoperative and intraoperative-PCI values. Fisher r-to-z transformation was used to compare correlations. RESULTS: A total of 488 patients were included. Of these, 34% had noninvasive appendiceal, 30% invasive appendiceal, 28% colorectal, and 8% PM histology. CT-PCI was correlated with intraoperative-PCI for patients with noninvasive and invasive appendiceal and colorectal histologies (r = 0.689, 0.554, and 0.571; all P < .001), but not PM (r = 0.188; P = .295). MRI-PCI was correlated with intraoperative-PCI for all histologies (non-invasive appendiceal: r = 0.591; P = .002; invasive appendiceal: r = 0.848; P < .001; colorectal: r = 0.729; P < .001; PM: r = 0.890; P = .007). Comparing CT and MRI, correlations were similar in noninvasive appendiceal and colorectal histologies; MRI was better for invasive appendiceal and PM (P = .005 and P = .021, respectively). Twenty-eight (6%) patients underwent an incomplete cytoreduction (cytoreduction score, 2-3). PCI greater than 15 was associated with cytoreduction score of 2 to 3 for both CT and MRI (CT-PCI: odds ratio, 3.0; P = .033; MRI-PCI: odds ratio, 7.6; P = .071). CONCLUSIONS: In this multi-institutional cohort, CT and MRI-PCI correlate well with intraoperative-PCI. MRI appears to be superior for invasive appendiceal and peritoneal mesothelioma. External validation in a larger population is needed.

Does Geographical Bias Impact the Match for General Surgery Residents?

OBJECTIVE: As the competitiveness of applicants for general surgery residency grows, it is becoming challenging for programs to differentiate qualified candidates with a genuine interest in matching at their institution. The purpose of this study was to examine geographic trends in the general surgery match in order to elicit regional biases and optimize applicant interview selection strategies. DESIGN: In this single-center retrospective study, geographical information regarding birth place, college, medical school, and final match institution for general surgery residency applicants was examined. SETTING: This study was set at the University of Cincinnati College of Medicine. PARTICIPANTS: All general surgery residency applicants interviewing at our institution between 2015-2017 were included. METHODS: Academic variables and geographical information were collected for all applicants in the cohort. Statistical analyses were performed using chi-square and logistic regression techniques to determine any association between geography and match outcomes. RESULTS: Of 198 applicants included in the analysis, approximately 25% matched at an institution located in the same state as their medical school. Total 75% of applicants matched at a residency program located less than 640 miles away from either their birth place, college, or medical school, while only 15% matched at an institution located over 1000 miles away and 4% matched over 2000 miles away. When examining applicant characteristics, there were no significant differences in gender, clerkship grade, United States Medical Licensing Exam scores, Alpha Omega Alpha Honor Society membership, or quality of recommendation letters between applicants who matched in the lowest and highest quartiles of distance to final residency program location. CONCLUSIONS: A significant proportion of general surgery applicants matched at institutions located in a region near either their birth place, college, or medical school. Given the limited number of interviews able to be offered by institutions and the associated opportunity costs, general surgery programs should consider regional biases when evaluating residency applicants.

Exploring the relationship between burnout and grit during general surgery residency: A longitudinal, single-institution analysis.

BACKGROUND: How burnout changes during general surgery residency remains unknown. METHODS: From 2015 to 2018, general surgery residents completed the Maslach Burnout Inventory and Grit Scale. Statistical analyses were adjusted for repeated measures and compared to the incoming intern level. RESULTS: Fifty-five residents participated in this study. Burnout rates varied by program level, with an increased risk occuring in the third clinical year (OR = 11.7, p = 0.03). Emotional exhaustion (EE) peaked during the first and third clinical years, depersonalization (DP) peaked during the first and second clinical years, and personal achievement (PA) reached a nadir during the third clinical year (all p < 0.05). Residents with burnout had lower grit scores compared to those without burnout (3.71 vs 4.02, p < 0.01). Increasing grit was linearly associated with decreasing EE, decreasing DP, and increasing PA (all p < 0.05). CONCLUSIONS: Burnout varies throughout surgical residency, and grit is inversely related to burnout.

Should We Be Doing Cytoreductive Surgery with HIPEC for Signet Ring Cell Appendiceal Adenocarcinoma? A Study from the US HIPEC Collaborative.

BACKGROUND: Appendiceal adenocarcinoma with signet ring cells (SCA) is associated with worse overall survival (OS), and it is unclear whether cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) should be pursued in this patient population. We assessed the prognostic implications of signet ring cells in patients with appendiceal adenocarcinoma and peritoneal carcinomatosis undergoing CRS-HIPEC. METHODS: The US HIPEC Collaborative, a 12-center, multi-institutional database of patients undergoing CRS-HIPEC, was reviewed for patients with SCA. Univariate and multivariate analyses were performed. RESULTS: Of 514 patients undergoing CRS-HIPEC for appendiceal adenocarcinoma, 125 (24%) had SCA. The SCA and non-SCA groups had similar baseline characteristics. SCA had worse OS compared with non-SCA (32.0 vs 91.4 months, p < 0.001). In univariate analysis for only SCA cases, there was worse OS in patients with poorly differentiated tumors, positive lymph nodes, LVI, PCI > 20, or incomplete cytoreduction (CC-2/3). However, multivariate analysis showed only positive lymph nodes (HR 1.14 [95% CI 1.00-1.31], p = 0.04), poor differentiation (5.60 [1.29-24.39], p = 0.02), and incomplete cytoreduction (4.90 [1.11-12.70], p = 0.03) were independently associated with decreased OS for SCA. CONCLUSION: While signet cells are a negative prognostic feature, they should not be a contraindication to CRS-HIPEC in patients with well-moderately differentiated tumors with negative lymph nodes, where complete cytoreduction can be achieved.

Readmissions After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a US HIPEC Collaborative Study.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. METHODS: The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. RESULTS: A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). CONCLUSIONS: In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.