Observations on the Representation of Asians in Surgical Training and Leadership.

INTRODUCTION: Diversity in medicine has a positive effect on outcomes, especially for Asian patients. We sought to evaluate representation of Asians across entry and leadership levels in surgical training. METHODS: Publicly accessible population data from 2018 to 2023 were collected from the US Census Bureau, the Association of American Medical Colleges, and the American Board of Surgery (ABS). Frequencies based on self-identified Asian status were identified, and proportions were calculated. RESULTS: The US census showed Asians constituted 4.9% of the US population in 2018 versus 6% in 2023. The proportion of Asian medical students rose from 21.6% to 24.8%; however, Asian surgical residency applicants remained constant at 20%. ABS certifications of Asians have increased from 13.7% to 18.5%. ABS examiners increased from 15.7% to 17.1%. CONCLUSIONS: In 5 years, Asians have made numeric gains in medical school and surgical training. However, Asian representation lags at Board examiner levels compared to the medical student population. The ABS has made recent efforts at transparency around examiner and examinee characteristics. A pillar of ensuring a well-trained surgical workforce to serve the public is to mandate that all surgical trainees and graduates undergo fair examinations, and are fairly assessed on their qualifications. Observed progress should further invigorate all surgical applicants, residents and leadership to take an even more active role in making surgery more diverse and welcoming to all, by including careful analyses of diversity at all levels.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Effective Mentoring Across Differences-Best Practices and Effective Models to Address the Needs of Underrepresented Trainees in Surgical Residency Programs.

BACKGROUND: Mentorship plays a critical role in the career development of surgical trainees and faculty. As the surgical workforce continues to diversify, mentoring trainees who differ) race, ethnicity, country of origin, socioeconomic status, educational background, religion, gender, sexual orientation or ability) can pose challenges to the experience for both mentor and mentee. OBJECTIVE: The aim of this manuscript is to introduce surgical educators to the systemic barriers faced by trainees and to models of effective mentorship. METHODS: At the 2022 APDS Meeting, a panel convened to highlight the current challenges of mentoring across differences and effective models for surgical educators. This paper highlights and expands the summary of this panel. RESULTS: Examples of novel mentoring models are described. CONCLUSIONS: Acknowledgment of barriers, Implementation of deliberate mentoring strategies, and collaboration with national surgical organizations and surgery departments and faculty may help to reduce physician attrition.

Emergent colectomy for colorectal cancer: A comparative analysis of open vs. minimally invasive approach.

INTRODUCTION: Emergent surgery for colorectal cancer (CRC) is associated with higher rates of morbidity and mortality and outcomes differ by surgical approach. METHODS: Our study compares short-term surgical outcomes of patients undergoing emergent colectomy for CRC using the open vs minimally invasive (MIS) approach. We performed a four-year review (2012-2015) of the ACS-NSQIP Colectomy dataset and included all adult patients with CRC who underwent emergent surgical intervention. Patients were stratified into groups based on surgical approach: Open and MIS (including laparoscopic and robotic). RESULTS: A total of 1855 (MIS: 279, Open: 1576) patients were included. Outcome measures were operative time, 30-day complications, 30-day readmission, and 30-day mortality. Multivariate Regression analysis was performed. Patients in the open group were more likely to be older (70y vs. 61y, p < 0.01), have higher ASA class, and were less likely to have received mechanical bowel preparation. On univariate analysis, patients in the MIS group had longer operative time (189 ± 41 min vs. 161 ± 69 min, p < 0.01). Patients in the open group had higher rates of mortality (6.7% vs. 3.8%, p < 0.01) and 30-day complications (28.1% vs. 16.7%, p < 0.01). On regression analysis, the open approach was independently associated with higher odds of 30-day mortality and 30-day complications. CONCLUSION: Given the lower overall mortality and complications, MIS colectomy may be a safer approach in the emergent treatment of patients with colorectal cancer.

Leadership Diversity in the Association of Program Directors in Surgery: A Report of Progress.

BACKGROUND: Across the last several years, numerous surgical departments and societies have focused on addressing the lack of diversity, equity, and inclusion (DEI) in the field. Since the Association of Program Directors in Surgery (APDS) Diversity and Inclusion Taskforce was created in 2017 (and solidified as a formal committee in 2018, herein referred to as the APDS-DIC), it has sought to address gaps in diversity at various phases of training and development from medical student to surgical leader. OBJECTIVE: In follow-up to a 2018 study that benchmarked leadership demographics of the APDS, this study analyzed how the APDS' efforts have aligned with recommended DEI strategies and whether this produced demographic changes in organizational leadership. METHODS: Fifteen years (2008-2022) of publicly available APDS annual meeting program data and APDS membership lists were analyzed. Leadership positions in the organization were examined by officer, program/vice chair, executive committee, and board of directors. A 2-tailed T-test compared differences in the average proportion of leaders from specific demographic groups before and after the APDS-DIC inception (2008-2016 vs. 2017-2022). RESULTS: APDS has 724 unique faculty and 140 resident members. The majority of both groups identified as White (68% of faculty and 58% of residents). Over 15 years, there have been 307 available leadership positions held by 67 individuals. All presidents and president-elect positions have been held by White surgeons; nearly 80% have been men. The average proportion of female leaders and the average proportion of racial/ethnic minority leaders were both significantly higher after implementation of the APDS-DIC in 2017 (p=0.0009 for gender and p=0.036 for racial/ethnic minorities). CONCLUSIONS: The APDS' commitment to DEI efforts and establishment of the APDS-DIC in 2017 was associated with a significant increase in women and non-White minorities in organizational leadership positions. The specific role of the APDS-DIC in propelling surgeons from underrepresented groups into leadership and promoting key DEI efforts is broadly applicable to other surgical organizations.

EQIP's First Year: A Step Closer to Higher Quality in Surgical Education.

OBJECTIVE: To describe the first year of the Educational Quality Improvement Program (EQIP) DESIGN: The Educational Quality Improvement Program (EQIP) was formed by the Association of Program Directors in Surgery (APDS) in 2018 as a continuous educational quality improvement program. Over 18 months, thirteen discrete goals for the establishment of EQIP were refined and executed through a collaborative effort involving leaders in surgical education. Alpha and beta pilots were conducted to refine the data queries and collection processes. A highly-secure, doubly-deidentified database was created for the ingestion of resident and program data. SETTING & PARTICIPANTS: 36 surgical training programs with 1264 trainees and 1500 faculty members were included in the dataset. 51,516 ERAS applications to programs were also included. Uni- and multi-variable analysis was then conducted. RESULTS: EQIP was successfully deployed within the timeline described in 2020. Data from the ACGME, ABS, and ERAS were merged with manually entered data by programs and successfully ingested into the EQIP database. Interactive dashboards have been constructed for use by programs to compare to the national cohort. Risk-adjusted multivariable analysis suggests that increased time in a technical skills lab was associated with increased success on the ABS's Qualifying Examination, alone. Increased time in a technical skills lab and the presence of a formal teaching curriculum were associated with increased success on both the ABS's Qualifying and Certifying Examination. Program type may be of some consequence in predicting success on the Qualifying Examination. CONCLUSIONS: The APDS has proved the concept that a highly secure database for the purpose of continuous risk-adjusted quality improvement in surgical education can be successfully deployed. EQIP will continue to improve and hopes to include an increasing number of programs as the barriers to participation are overcome.

The APDS General Surgery Education Quality Improvement Program (EQIP).

BACKGROUND: Although the ACGME has called for outcomes-based evaluation of residency programs, few metrics or benchmarks exist connecting educational processes with resident educational outcomes. To address this deficiency, a national Education Quality Improvement Program (EQIP) for General Surgery training is proposed. METHODS: We describe the initial efforts to create this platform. In addition, a national survey was administered to 330 Program Directors to assess their interest in and concerns about a continuous educational quality improvement project. RESULTS: We demonstrate that through a collaborative process and the support of the Association of Program Directors in Surgery (APDS), we were able to develop the groundwork for a national surgical educational improvement project, now called EQIP. The survey response rate was 45.8% (152 of 332 programs) representing a mix of university (55.3%), university-affiliated (18.4%), independent (24.3%), and military (2.0%) programs. Most respondents (66.2%) had not previously heard of EQIP. Most respondents (69.7%) believe that educational outcomes can be measured. The majority of respondents indicated they believed EQIP could be successful (57%). Only 2.3% thought EQIP would not be successful. Almost all programs (98.7%) expressed a willingness to participate, although 19.1% did not believe that they had adequate resources to participate. CONCLUSION: The APDS EQIP platform holds promise as a useful and achievable method to obtain educational outcomes data. These data can be used as a basis for continuous surgical educational quality improvement. General Surgery Program Directors have expressed enthusiasm for EQIP and are willing to participate in the program examining outcomes of General Surgery training programs, with an ultimate goal of improving overall residency training.

Early-Onset Colorectal Cancer.

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States, and the incidence of early-onset CRC (EOCRC, <50 years old) has been steadily increasing over the past 30 years. This article provides a comprehensive review of EOCRC traits, including incidence rates and patterns, tumor biologic differences compared to late-onset CRC, dietary risk factors, relationship between CRC and the microbiome, and patient survival outcomes associated with EOCRC. These factors carry importance in determining diagnostic, prognostic, disease monitoring, and treatment planning practices for EOCRC in the future. They also serve as guides for optimizing CRC screening recommendations.

Delphi Consensus on Intraoperative Technical/Surgical Aspects to Prevent Surgical Site Infection after Colorectal Surgery.

BACKGROUND: Previous studies have focused on the development and evaluation of care bundles to reduce the risk of surgical site infection (SSI) throughout the perioperative period. A focused examination of the technical/surgical aspects of SSI reduction during CRS has not been conducted. This study aimed to develop an expert consensus on intraoperative technical/surgical aspects of SSI prevention by the surgical team during colorectal surgery (CRS). STUDY DESIGN: In a modified Delphi process, a panel of 15 colorectal surgeons developed a consensus on intraoperative technical/surgical aspects of SSI prevention undertaken by surgical personnel during CRS using information from a targeted literature review and expert opinion. Consensus was developed with up to three rounds per topic, with a prespecified threshold of ≥70% agreement. RESULTS: In 3 Delphi rounds, the 15 panelists achieved consensus on 16 evidence-based statements. The consensus panel supported the use of wound protectors/retractors, sterile incision closure tray, preclosure glove change, and antimicrobial sutures in reducing SSI along with wound irrigation with aqueous iodine and closed-incision negative pressure wound therapy in high-risk, contaminated wounds. CONCLUSIONS: Using a modified Delphi method, consensus has been achieved on a tailored set of recommendations on technical/surgical aspects that should be considered by surgical personnel during CRS to reduce the risk of SSI, particularly in areas where the evidence base is controversial or lacking. This document forms the basis for ongoing evidence for the topics discussed in this article or new topics based on newly emerging technologies in CRS.

Surgical Outcomes in Patients With Preoperative Anemia Undergoing Colectomy for Colon Cancer.

INTRODUCTION: Preoperative anemia is relatively common in colon cancer patients; however, its impact on short-term surgical outcomes is not well established. The aim of our study was to evaluate short-term surgical outcomes in colon cancer patients with preoperative anemia undergoing colectomy. METHODS: We performed a 4-year analysis of the ACS-NSQIP and included all adult patients who underwent colectomy for colon cancer. Patients were stratified into two groups based on preoperative anemia (Preop Anemia, No Preop Anemia). Our outcome measures were 30-day complications, 30-day unplanned readmissions, and 30-day mortality. RESULTS: A total of 35,243 colon cancer patients who underwent colectomy were included in the analysis, of whom 50.4% had preoperative anemia. The mean age was 65 ± 13 years and the mean hemoglobin level was 12 ± 2 g/dL. Patients in the anemia group were more likely to be African American, have higher ASA class ≥3, and were more likely to receive at least 1 unit of packed red blood cells preoperatively (7.1% versus 0.3%, P < 0.01). Patients in the anemia group had higher rates of 30-day complications (34.5% versus 16.6%, P < 0.01), 30-day readmission related to the principal procedure (11.7% versus 8.7%, P < 0.01), and 30-day mortality (3.1% versus 1%, P < 0.01). On regression analysis, preoperative anemia was independently associated with higher odds of 30-day complications (P < 0.01), but not 30-day readmission, or 30-day mortality (P = 0.464 and P = 0.362 respectively). CONCLUSIONS: Preoperative anemia appears to be associated with postoperative complications. Preoperatively optimizing hemoglobin levels may lead to improved outcomes.

The Role of Implicit Bias in Surgical Resident Evaluations.

BACKGROUND: Implicit bias is a key factor preventing the advancement and retention of women and underrepresented minorities in academic surgery. PURPOSE: We examined the role of implicit bias in the technical component of the residency performance evaluation. The Fundamentals of Laparoscopic Surgery (FLS) score, an objective measure of technical performance, was compared to the subjective technical skills (TS) score given by attending surgeons. PROCEDURES: FLS scores and the average TS scores from chief resident evaluations at a university program were analyzed from 2015 to 2019 (n = 29 residents; female 22%, underrepresented minorities 27%).  The average TS score for each resident was calculated, scores dichotomized above and below the mean for the program and analyzed across gender and racial identity. MAIN FINDINGS: There were no significant differences in FLS or TS scores between male and female trainees or racial identity. The Kappa correlation coefficient between the 2 dichotomized scores was significantly lower for female (-0.50) versus male (0.23) trainees (p < 0.01); it was not significantly different between racial groups (p = 0.34). PRINCIPAL CONCLUSIONS: There was statistically significant difference in agreement between the FLS and TS scores of individual female and male trainees, suggesting the presence of implicit bias in our pilot study. Further research with a larger sample size is warranted. OBJECTIVE: To investigate the presence of implicit bias against women and underrepresented minorities in the technical component of the residency performance evaluation. We hypothesized that women and underrepresented racial minorities would have lower subjective technical skills (TS) scores as compared to their objective FLS scores, relative to the mean for the training program. DESIGN: FLS scores and the average TS scores from chief resident performance evaluations were analyzed from 2015-2019. Both FLS and the average TS scores were dichotomized above and below the mean for the program and analyzed across gender and racial identity.  Research was approved by institutional IRB. SETTING: This study was conducted at the University of Arizona General Surgery Residency Program at Banner University Medical Center in Tucson, Arizona. This is a tertiary care university training program. PARTICIPANTS: Educational records of graduated general surgery chief residents from 2015 to 2019 were accessed for the study. We analyzed 37 TS scores from attending performance evaluations and 29 FLS scores reported to the program during the study period (22% female, 27% underrepresented racial minorities). RESULTS: There were no significant differences in FLS or TS scores between male and female trainees or racial identity. The Kappa correlation coefficient between the 2 dichotomized scores was significantly lower for female (-0.50) versus male (0.23) trainees (p < 0.01); it was not significantly different between racial groups (p = 0.34). CONCLUSIONS: There was a statistically significant difference in agreement between the FLS and TS score of individual female and male trainees, suggesting the presence of implicit bias in this pilot study. Further research with a larger sample size is warranted.

Colorectal cancer mortality after spinal cord injury.

Context: Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the US. There is paucity of data regarding CRC and the spinal cord injury (SCI) community. Persons with SCI have suboptimal rates of colonoscopies and face extensive barriers to care. The aim of our study was to compare CRC mortality in persons with SCI to CRC mortality in the general population.Design: A prospective follow-up study.Setting: Analysis of the National SCI database.Participants: 54,965 persons with SCI.Interventions: Not applicable.Outcome Measures: Current survival status and causes of death were determined. The expected number of CRC deaths was calculated for the general US population, using ICD-10 codes. Standardized mortality ratios (SMR) were calculated as the ratio of observed to expected CRC deaths stratified by current age, sex, race, time post-injury and neurologic group.Results: The CRC mortality was 146 persons out of 54,965 persons with SCI. The overall SMR was determined to be 1.11 (95% CI [0.94, 1.31]). Among subgroups, one finding was significant and this was for patients with injury level C1-4 with an American Spinal Injury Association Impairment Scale Grade of A, B or C with an SMR of 1.68 ([95% CI [1.03-2.61]).Conclusion: Although persons with SCI receive suboptimal rates of preventative care screenings and report extensive barriers to care, overall, they are not at an increased risk of CRC mortality. The current recommendations for CRC screening should be continued for these individuals while reducing barriers to care.

Cartilage Oligomeric Matrix Protein, COMP may be a Better Prognostic Marker Than CEACAM5 and Correlates With Colon Cancer Molecular Subtypes, Tumor Aggressiveness and Overall Survival.

BACKGROUND: New tumor biomarkers are needed to improve the management of colon cancer (CC), the second leading cause of cancer-related deaths in the United States. Carcinoembryonic Antigen (CEA), the translated protein of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) gene, is used as a biomarker for CC. Cartilage Oligomeric Matrix Protein (COMP) is overexpressed in CC compared to normal colon tissues. This study aims to evaluate the expression of COMP by disease stage, consensus molecular subtype (CMS), its impact on disease outcomes, and comparison to CEACAM5. MATERIALS AND METHODS: RNA-seq data from 456 CC The Cancer Genome Atlas samples and 41 matching control samples were analyzed for COMP expression and CEACAM5 expression. We stratified tumor samples by stage (I-IV), subtype (CMS1-CMS4), tumor location, and Kirsten RAt Sarcoma (KRAS) mutant status and three quartiles were established based on COMP expression. Kaplan Meier survival outcomes were evaluated. RESULTS: COMP expression was significantly higher in tumor samples, with elevation of expression occurring in stage I and significantly increasing in stage IV. Increased COMP expression occurs in CMS4 with relatively low expression in CMS3. No significant expression difference was attributed to tumor location and KRAS mutant status. Compared to CEACAM5, COMP was a stronger molecular marker across stages and subtypes. CMS4 was associated with the high COMP expression, and higher levels of COMP were associated with poorer overall survival, disease-specific survival, and tumor progression-free intervals. CMS2 and 3 were associated with low expression and better survival. CONCLUSION: COMP is a potential molecular biomarker for CC and may be superior to CEA as an indicator of CC.

Incidence and predictors of brain metastasis in colorectal cancer patients.

PURPOSE: Brain metastasis (BM) in colorectal cancer patients is rare and is associated with dismal outcomes. Our study aims to evaluate the incidence and predictors of BM in patients with colorectal cancer. METHODS: We performed a retrospective analysis (2010-2017) of patients with a primary diagnosis of colorectal cancer (CRC). Patients were stratified into two groups (BM vs. No-BM). Outcome measures were the incidence and predictors of BM. Multivariate logistic regression analysis was performed. RESULTS: A total of 230,806 patients were analyzed. A total of 0.30% (n = 691) of the patients were found to have BM. On multivariate logistics regression, bone (OR: 5.39 [3.36-8.65], p < 0.001), lung (OR: 3.75 [2.67-5.28], < 0.001), and distant node metastasis (OR: 32.75 [20.47-52.41], p < 0.001) were independent predictors of BM. CONCLUSION: Our study supports the low incidence of brain metastasis in patients with colorectal cancer. A unique set of characteristics is identified to confer an increased risk of brain metastases.

Race, Gender, and International Medical Graduates: Leadership Trends in Academic Surgical Societies.

BACKGROUND: Non-White and female surgeons are underrepresented in academic surgery faculty. We hypothesized that the leadership of major U.S. regional and national general surgery societies reflects these same racial and gender disparities. We suspected that attending a medical school or residency program with academic prestige would be more common for surgeons from underrepresented backgrounds. MATERIALS AND METHODS: Race/ethnicity and gender of the 2020-21 executive council members and 2012-21 society presidents of 25 major general surgery societies (7 regional, 18 national) was assessed. Academic prestige was determined by reputational top 25 programs, identified using U.S. News and World Report and Doximity rankings for medical school and residency, respectively. RESULTS: Surgical society executive council members (n = 204) were predominantly White (75.5%) and male (67.2%). The 50 non-White council members were Asian (n = 37), Black (n = 7), and Latinx (n = 6). 14 (6.9%) were international medical graduates (IMGs). 56.4% attended a school or program ranked in the Top 25 (n = 115). Surgical society presidents 2012-21 (n = 242) have been mostly White (87.6%) and male (83.4%). Non-White, male surgical society presidents were Asian (n = 13), Black (n = 9), and Latino (n = 6). Of the 41 female surgery society presidents, 92.7% were White, 7.3% (n = 3) Asian, and none Black or Latina. 13 were IMGs (5.3%). 55.0% of society presidents attended Top 25 (n = 133) schools or programs. The three non-White, female presidents all attended Top 25 schools/programs (100%). Of the 15 unique individuals who were male, non-White presidents, 12 attended top 25 schools or programs (80%). CONCLUSION: Women, non-White surgeons, and IMGs are underrepresented in U.S. surgical society leadership. Increasing racial diversity in U.S. surgical society leadership may require intentionality in mentorship and sponsorship, particularly for surgeons who did not attend prestigious schools or programs.

Early Detection and Remediation of Problem Learners.

There are myriad types of problem learners in surgical residency and most have difficulty in more than 1 competency. Programs that use a standard curriculum of study and assessment are most successful in identifying struggling learners early. Many problem learners lack appropriate systems for study; a multidisciplinary educational team that is separate from the team that evaluates the success of remediation is critical. Struggling residents who require formal remediation benefit from performance improvement plans that clearly outline the issues of concern, describe the steps required for remediation, define success of remediation, and outline consequences for failure to remediate appropriately.

Molecular Pathways Associated with Kallikrein 6 Overexpression in Colorectal Cancer.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The high mortality of CRC is related to its ability to metastasize to distant organs. The kallikrein-related peptidase Kallikrein 6 (KLK6) is overexpressed in CRC and contributes to cancer cell invasion and metastasis. The goal of this study was to identify KLK6-associated markers for the CRC prognosis and treatment. Tumor Samples from the CRC patients with significantly elevated KLK6 transcript levels were identified in the RNA-Seq data from Cancer Genome Atlas (TCGA) and their expression profiles were evaluated using Gene Ontology (GO), Phenotype and Reactome enrichment, and protein interaction methods. KLK6-high cases had a distinct spectrum of mutations in titin (TTN), APC, K-RAS, and MUC16 genes. Differentially expressed genes (DEGs) found in the KLK6-overexpressing CRCs were associated with cell signaling, extracellular matrix organization, and cell communication regulatory pathways. The top KLK6-interaction partners were found to be the members of kallikrein family (KLK7, KLK8, KLK10), extracellular matrix associated proteins (keratins, integrins, small proline rich repeat, S100A families) and TGF-ß, FOS, and Ser/Thr protein kinase signaling pathways. Expression of selected KLK6-associated genes was validated in a subset of paired normal and tumor CRC patient-derived organoid cultures. The performed analyses identified KLK6 itself and a set of genes, which are co-expressed with KLK6, as potential clinical biomarkers for the management of the CRC disease.

Does preoperative neoadjuvant chemotherapy impact short-term surgical outcomes in patients with locally advanced colon cancer?

BACKGROUND: Preoperative neoadjuvant chemotherapy (NAC) for colon cancer in advanced stages is associated with improved outcomes and tumor regression. The aim of our study was to identify outcomes in patients with colon cancer who received preoperative NAC. METHODS: A 4-year analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) was performed. We included patients with locally advanced colon cancer (non-metastatic T3, T4 with or without nodal involvement) who underwent colon cancer resection. Patients were stratified into two groups (NAC and No-NAC). Our outcome measures were anastomotic leaks, hospital length of stay (LOS), 30-day complications, 30-day mortality, and 30-day readmissions. We performed a multi-variable logistic regression analysis. RESULTS: We analyzed 90,055 patients of which 7694 (NAC: 7.8 % (n = 599) and No-NAC: 92.2% (n = 7095)) met the inclusion criteria and included in the analysis. Mean age was 67 ± 13 years, 51% were males, and 72% were whites. Patients in the NAC group were more likely to be younger (60 ± 12 years vs. 68 ± 13 years, p < 0.01) and males (62% vs. 50%, p < 0.01) compared to No-NAC. On regression analysis, preoperative NAC was independently associated with higher odds of anastomotic leak (OR 1.35 [1.05-1.97], p = 0.03) and 30-day readmission (OR 1.54 [1.24-2.05], p < 0.01) in reference to No-NAC. However, no association was found between NAC and 30-day complications and 30-day mortality. CONCLUSIONS: Preoperative NAC might be associated with adverse outcomes of anastomotic leaks and 30-day readmissions, however does not appear to impact 30-day complications nor 30-day mortality.