ST6GAL1 is associated with poor response to chemoradiation in rectal cancer.

INTRODUCTION: Colorectal cancer is the third most common cause of cancer death. Rectal cancer makes up a third of all colorectal cases. Treatment for locally advanced rectal cancer includes chemoradiation followed by surgery. We have previously identified ST6GAL1 as a cause of resistance to chemoradiation in vitro and hypothesized that it would be correlated with poor response in human derived models and human tissues. METHODS: Five organoid models were created from primary human rectal cancers and ST6GAL1 was knocked down via lentivirus transduction in one model. ST6GAL1 and Cleaved Caspase-3 (CC3) were assessed after chemoradiation via immunostaining. A tissue microarray (TMA) was created from twenty-six patients who underwent chemoradiation and had pre- and post-treatment specimens of rectal adenocarcinoma available at our institution. Immunohistochemistry was performed for ST6GAL1 and percent positive cancer cell staining was assessed and correlation with pathological grade of response was measured. RESULTS: Organoid models were treated with chemoradiation and both ST6GAL1 mRNA and protein significantly increased after treatment. The organoid model targeted with ST6GAL1 knockdown was found to have increased CC3 after treatment. In the tissue microarray, 42 percent of patient samples had an increase in percent tumor cell staining for ST6GAL1 after treatment. Post-treatment percent staining was associated with a worse grade of treatment response (p = 0.01) and increased staining post-treatment compared to pre-treatment was also associated with a worse response (p = 0.01). CONCLUSION: ST6GAL1 is associated with resistance to treatment in human rectal cancer and knockdown in an organoid model abrogated resistance to apoptosis caused by chemoradiation.

Preserving the Pipeline of Surgeon Scientists: The Role of a Structured Research Curriculum.

INTRODUCTION: With shrinking National Institute of Health support, increased clinical demands, and less time for research training during residency, the future of surgeon scientists is in jeopardy. We evaluate the role of a structured research curriculum and its association with resident academic productivity. METHODS: Categorical general surgery residents who matched between 2005 and 2019 at our institution were analyzed (n = 104). An optional structured research curriculum, including a mentor program, grant application support, didactic seminars, and travel funding was implemented in 2016. Academic productivity, including the number of publications and citations, was compared between residents who started in or after 2016 (postimplementation, n = 33) and those before 2016 (preimplementation, n = 71). Descriptive statistics, Mann-Whitney U test, multivariable logistic regression, and inverse probability treatment weighting were performed. RESULTS: The postimplementation group had more female (57.6% versus 31.0%, P = 0.010), and nonwhite (36.4% versus 5.6%, P < 0.001) residents and had more publications and citations at the start of residency (P < 0.001). Postimplementation residents were more likely to choose academic development time (ADT) (66.7% versus 23.9%, P < 0.001) and had higher median (IQR) number of publications (2.0 (1.0-12.5) versus 1.0 (0-5.0), P = 0.028) during residency. After adjusting the number of publications at the start of residency, multivariable logistic regression analysis showed that the postimplementation group was five times more likely to choose ADT (95% CI 1.7-14.7, P = 0.04). Further, inverse probability treatment weighting revealed an increase of 0.34 publications per year after implementing the structured research curriculum among residents who chose ADT (95% CI 0.1-0.9, P = 0.023). CONCLUSIONS: A structured research curriculum was associated with increased academic productivity and surgical resident participation in dedicated ADT. A structured research curriculum is effective and should be integrated into residency training to support the next generation of academic surgeons.

Racial Differences in Aging-Related Deficits Among Older Adults With Colorectal Cancer.

BACKGROUND: Despite the known influences of both race- and aging-related factors in colorectal cancer outcomes and mortality, limited literature is available on the intersection between race and aging-related impairments. OBJECTIVE: To explore racial differences in frailty and geriatric deficit subdomains among patients with colorectal cancer. DESIGN: Retrospective study using data from the Cancer and Aging Resilience Evaluation registry. SETTINGS: A comprehensive cancer center in the Deep South. PATIENTS: Older adults (aged ≥60 years) with colorectal cancer. MAIN OUTCOME MEASURES: Measure of frailty and geriatric assessment subdomains of physical function, functional status, cognitive complaints, psychological function, and health-related quality of life. RESULTS: Black patients lived in areas with a higher social vulnerability index compared to White patients (0.69 vs 0.49; p < 0.01) and had limited social support more often (54.5% vs 34.9%; p = 0.01). After adjustment for age, cancer stage, comorbidities, and social vulnerability index, Black patients were found to have a higher rate of frailty than White patients (adjusted OR 3.77; 95% CI, 1.76-8.18; p = 0.01). In addition, Black patients had more physical limitations (walking 1 block: adjusted OR 1.93; 95% CI, 1.02-3.69; p = 0.04), functional limitations (activities of daily living: adjusted OR 3.21; 95% CI, 1.42-7.24; p = 0.01), and deficits in health-related quality of life (poor global self-reported health: adjusted OR 2.45; 95% CI, 1.23-5.13; p = 0.01). Similar findings were shown after stratification by stage I to III vs IV. LIMITATIONS: Retrospective study at a single institution. CONCLUSIONS: Among older patients with colorectal cancer, Black patients were more likely to be frail than White patients, with deficits observed specifically in physical function, functional status, and health-related quality of life. Geriatric assessment may provide an important tool in addressing racial inequities in colorectal cancer. DIFERENCIAS RACIALES EN LOS DFICITS RELACIONADOS CON EL ENVEJECIMIENTO ENTRE ADULTOS MAYORES CON CNCER COLORRECTAL: ANTECEDENTES: A pesar de las influencias conocidas de los factores relacionados con la raza y el envejecimiento en los resultados y la mortalidad del cáncer colorectal, hay muy poca literatura sobre la intersección entre los impedimentos relacionados con la raza y el envejecimiento.OBJETIVO: El objetivo era explorar las diferencias raciales en los subdominios de fragilidad y déficit geriátrico entre los pacientes con cáncer colorectal.DISEÑO: Estudio retrospectivo utilizando datos del registro Cancer and Aging Resilience Evaluation.AJUSTES: Un centro oncológico integral en el Sur Profundo.PACIENTES: Adultos mayores (≥60 años) con cáncer colorrectal de raza Negra o Blanca.PRINCIPALES MEDIDAS DE RESULTADO: Medida compuesta de fragilidad y subdominios de evaluación geriátrica de función física, estado funcional, quejas cognitivas, función psicológica y calidad de vida relacionada con la salud.RESULTADOS: De los 304 pacientes incluidos, el 21,7% (n = 66) eran negros y la edad media era de 69 años. Los pacientes negros vivían en áreas con un índice de vulnerabilidad social (SVI) más alto en comparación con los pacientes blancos (SVI 0,69 vs 0,49; p < 0,01) y con mayor frecuencia tenían apoyo social limitado (54,5% vs 34,9%; p = 0,01). Después de ajustar por edad, estadio del cáncer, comorbilidades y SVI, los pacientes de raza negra tenían una mayor tasa de fragilidad en comparación con los pacientes de raza blanca (ORa 3,77, IC del 95%: 1,76-8,18; p = 0,01). Además, los pacientes negros tenían más limitaciones físicas (caminar 1 cuadra: ORa 1,93, IC 95% 1,02-3,69; p = 0,04), limitaciones funcionales (actividades de la vida diaria: ORa 3,21, IC 95% 1,42-7,24; p = 0,01 ) y déficits en la calidad de vida relacionada con la salud (mala salud global autoinformada: ORa 2,45, IC 95% 1,23-5,13; p = 0,01). Las quejas cognitivas y las funciones psicológicas no difirieron según la raza (p > 0,05). Se mostraron hallazgos similares después de la estratificación por estadio I-III frente a IV.LIMITACIONES: Estudio retrospectivo en una sola institución.CONCLUSIONES: Entre los pacientes mayores con cáncer colorrectal, los pacientes negros tenían más probabilidades que los pacientes blancos de ser frágiles, observándose déficits específicamente en la función física, el estado funcional y la calidad de vida relacionada con la salud. La evaluación geriátrica puede proporcionar una herramienta importante para abordar las desigualdades raciales en el cáncer colorrectal.

Inhibition of DNA-PK may improve response to neoadjuvant chemoradiotherapy in rectal cancer.

Treatment of locally advanced rectal cancer includes chemoradiation and surgery, but patient response to treatment is variable. Patients who have a complete response have improved outcomes; therefore, there is a critical need to identify mechanisms of resistance to circumvent them. DNA-PK is involved in the repair of DNA double-strand breaks caused by radiation, which we found to be increased in rectal cancer after treatment. We hypothesized that inhibiting this complex with a DNA-PK inhibitor, Peposertib (M3814), would improve treatment response. We assessed pDNA-PK in a rectal cancer cell line and mouse model utilizing western blotting, viability assays, γH2AX staining, and treatment response. The three treatment groups were: standard of care (SOC) (5-fluorouracil (5FU) with radiation), M3814 with radiation, and M3814 with SOC. SOC treatment of rectal cancer cells increased pDNA-PK protein and increased γH2AX foci, but this was abrogated by the addition of M3814. Mice with CT26 tumors treated with M3814 with SOC did not differ in average tumor size but individual tumor response varied. The clinical complete response rate improved significantly with the addition of M3814 but pathological complete response did not. We investigated alterations in DNA repair and found that Kap1 and pATM are increased after M3814 addition suggesting this may mediate resistance. When the DNA-PK inhibitor, M3814, is combined with SOC treatment, response improved in some rectal cancer models but an increase in other repair mechanisms likely diminishes the effect. A clinical trial is ongoing to further explore the role of DNA-PK inhibition in rectal cancer treatment.

Sialyltransferase ST6GAL-1 mediates resistance to chemoradiation in rectal cancer.

Locally advanced rectal cancer is typically treated with chemoradiotherapy followed by surgery. Most patients do not display a complete response to chemoradiotherapy, but resistance mechanisms are poorly understood. ST6GAL-1 is a sialyltransferase that adds the negatively charged sugar, sialic acid (Sia), to cell surface proteins in the Golgi, altering their function. We therefore hypothesized that ST6GAL-1 could mediate resistance to chemoradiation in rectal cancer by inhibiting apoptosis. Patient-derived xenograft and organoid models of rectal cancer and rectal cancer cell lines were assessed for ST6GAL-1 protein with and without chemoradiation treatment. ST6GAL-1 mRNA was assessed in untreated human rectal adenocarcinoma by PCR assays. Samples were further assessed by Western blotting, Caspase-Glo apoptosis assays, and colony formation assays. The presence of functional ST6GAL-1 was assessed via flow cytometry using the Sambucus nigra lectin, which specifically binds cell surface α2,6-linked Sia, and via lectin precipitation. In patient-derived xenograft models of rectal cancer, we found that ST6GAL-1 protein was increased after chemoradiation in a subset of samples. Rectal cancer cell lines demonstrated increased ST6GAL-1 protein and cell surface Sia after chemoradiation. ST6GAL-1 was also increased in rectal cancer organoids after treatment. ST6GAL-1 knockdown in rectal cancer cell lines resulted in increased apoptosis and decreased survival after treatment. We concluded that ST6GAL-1 promotes resistance to chemoradiotherapy by inhibiting apoptosis in rectal cancer cell lines. More research will be needed to further elucidate the importance and mechanism of ST6GAL-1-mediated resistance.

Ileostomy Patients Using Patient Engagement Technology Experience Decreased Length of Stay.

Patients who undergo colorectal surgery, particularly, construction of a new ileostomy, are known to have longer length of stay (LOS) and increased readmissions. With the increased availability of patient engagement technology (PET), we hypothesized that because PET facilitates education before and after surgery, ileostomy patients who used PET would have decreased LOS without increasing readmissions. Variables were obtained from the National Surgical Quality Improvement Program (NSQIP) database for patients undergoing ileostomy construction. Study patients were categorized into three groups: pre-PET (patients prior to PET), non-PET (patients who did not use PET), and PET users (patients who used PET). Univariate analysis of patient and surgical characteristics, LOS, ED visits, and readmissions and multivariable modeling of potential predictors of LOS were performed. There were 106 patients in the pre-PET, 51 in the PET, and 108 in the non-PET and cohorts were similar except pre-op diagnosis. Length of stay was lower for the PET cohort (p = 0.0001), with no significant difference in readmission or ED visits. On multivariable analysis, we identified the PET cohort as an independent predictor of shorter LOS relative to non-PET and pre-PET (p = 0.007 and p = 0.02, respectively). Similarly, patients had significantly shorter LOS who had a diagnosis of neoplasm as compared to IBD (p = 0.03). Hypertension requiring medication (p = 0.001) and Black race relative to White race (p = 0.002) were independent predictors of longer LOS. In this study of ileostomy patients, we have shown that use of PET is an independent predictor of decreased LOS without increased ED visits or readmissions.

Multidisciplinary clinics for colorectal cancer may not provide more efficient coordination of care.

BACKGROUND: This retrospective study compares a multidisciplinary clinic (MDC) to standard care for time to treatment of colorectal cancer. METHODS: We queried our institutional ACS-NSQIP database for patients undergoing surgery for colorectal cancer from 2017 to 2020. Patients were stratified by initial clinic visit (MDC vs control). Primary endpoint was the time to start treatment (TST), either neoadjuvant therapy or surgery, from the date of diagnosis by colonoscopy. RESULTS: A total of 405 patients were evaluated (115 MDC, 290 Control). TST from diagnosis was not significantly shorter for the MDC cohort (MDC 30 days, Control 37 days; p = 0.07) even when stratified by type of initial treatment of neoadjuvant therapy (MDC 30, Control 34 days; p = 0.28) or surgery (MDC 32.5 days, Control 38 days; p = 0.35). CONCLUSION: Implementation of an MDC provides insignificant reduction in delay to start treatment for colorectal cancer patients as compared to standard care colorectal surgery clinics. CLASSIFICATION: Colorectal.

Circulating Tumor DNA Predicts Pathologic and Clinical Outcomes Following Neoadjuvant Chemoradiation and Surgery for Patients With Locally Advanced Rectal Cancer.

PURPOSE: This study was designed to assess the ability of perioperative circulating tumor DNA (ctDNA) to predict surgical outcome and recurrence following neoadjuvant chemoradiation for locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Twenty-nine patients with newly diagnosed LARC treated between January 2014 and February 2018 were enrolled. Patients received long-course neoadjuvant chemoradiation prior to surgery. Plasma ctDNA was collected at baseline, preoperatively, and postoperatively. Next-generation sequencing was used to identify mutations in the primary tumor, and mutation-specific droplet digital polymerase chain reaction was used to assess mutation fraction in ctDNA. RESULTS: The median age was 54 years. The overall margin-negative, node-negative resection rate was 73% and was significantly higher among patients with undetectable preoperative ctDNA (n = 17, 88%) versus patients with detectable preoperative ctDNA (n = 9, 44%; P = .028). Undetectable ctDNA was also associated with more favorable neoadjuvant rectal scores (univariate linear regression, P = .029). Recurrence-free survival (RFS) was calculated for the subset (n = 19) who both underwent surgery and had postoperative ctDNA available. At a median follow-up of 20 months, patients with detectable postoperative ctDNA experienced poorer RFS (hazard ratio, 11.56; P = .007). All patients (4 of 4) with detectable postoperative ctDNA recurred (positive predictive value = 100%), whereas only 2 of 15 patients with undetectable ctDNA recurred (negative predictive value = 87%). CONCLUSION: Among patients treated with neoadjuvant chemoradiation for LARC, patients with undetectable preoperative ctDNA were more likely to have a favorable surgical outcome as measured by the rate of margin-negative, node-negative resections and neoadjuvant rectal score. Furthermore, we have confirmed prior reports indicating that detectable postoperative ctDNA is associated with worse RFS. Future prospective study is needed to assess the potential for ctDNA to assist with personalizing treatment for LARC.

NIH Funding of Researchers in Surgery: Decreased Career Development Awards Over Time.

BACKGROUND: Over time, NIH funding has become increasingly competitive. In addition, academic surgeons' research competes with time required for patient care, operating, and administrative work. Due to these competing interests for surgeons, we hypothesize that the percentage of NIH grants awarded to researchers from departments of surgery is decreasing. METHODS: The NIH Research Portfolio Online Reporting Tool was queried for the number and value of new and renewal R01 grants, and career development awards noting which surgery departments received awards from 1998 to -2018. Statistical analysis was performed using univariate and multivariable logistic regression. RESULTS: The number of career development awards granted to researchers from departments of surgery decreased significantly over time (P = 0.007) while new R01's and R01 renewal awards were stable. The number of grants awarded to researchers from all procedural departments were compared to non-procedural departments and again, career development awards decreased significantly (P = 0.005) over time but new R01's and R01 renewals stayed stable. Looking at the difference in average dollar amount received for new R01, renewal R01, or career development awards between department of surgery awardees and non-surgery over time, there was no significant difference. CONCLUSIONS: NIH funding is becoming increasingly competitive and surgeons have many competing interests. Our study found that there has been a significant decrease in career development awards to department of surgery awardees and procedural specialists. The decrease in receipt of these awards is particularly concerning given that they are meant to provide protected time for developing researchers and thus have potential consequences for future research.

The impact of an enhanced recovery program (ERP) on the costs of colorectal surgery.

BACKGROUND: Enhanced Recovery Programs (ERPs) benefit patients but their effects on healthcare costs remain unclear. This study aimed to investigate the costs associated with a colorectal ERP in a large academic health system. METHODS: Patients who underwent colorectal surgery from 2012 to 2014 (pre-ERP) and 2015-2017 (ERP) were propensity score matched based on patient and operative-level characteristics. Primary outcomes were median variable, fixed, and total costs. Secondary outcomes included length-of-stay (LOS), readmissions, and postoperative complications (POCs). RESULTS: 616 surgical cases were included. Patient and operative-level characteristics were similar between the cohorts. Variable costs were $1028 less with ERP. ERP showed savings in nursing, surgery, anesthesiology, pharmacy, and laboratory costs, but had higher fixed costs. Total costs between the two groups were similar. ERP patients had significantly shorter LOS (-1 day, p < 0.01), but similar 30-day readmission rates and overall POCs. CONCLUSIONS: Implementation of an ERP for colorectal surgery was associated with lower variable costs compared to pre-ERP.

Racial disparities exist in surgical outcomes for patients with inflammatory bowel disease.

BACKGROUND: Racial disparities in surgical outcomes exist for Black patients with IBD compared to White patients. However, previous studies fail to include other racial/ethnic populations. We hypothesized these disparities exist for Hispanic and Asian patients. METHODS: This is a retrospective cohort study of patients undergoing surgery for IBD using the American College of Surgeons National Surgical Quality Improvement Program (ACS- NSQIP) database (2005-2017). Bivariate comparisons and adjusted multivariable regressions were performed to evaluate associations between race and outcomes. RESULTS: Of 23,901 patients with IBD, the racial/ethnic makeup were: 88.7% White, 7.6% Black, 2.4% Hispanic and 1.4% Asian. Overall mean LOS was 8 days (SD 8.2) and significantly varied between groups (8d for White, 10d for Black, 8.5d for Hispanic, and 11.1d for Asian; p < 0.001). Hispanic patients had the highest odds of readmission (OR: 1.4; 95% CI 1.1-1.8). Black patients had increased odds of renal insufficiency (OR: 1.8; 95% CI 1.1-2.9), bleeding requiring transfusions (OR: 1.7; 95% CI 1.4-1.9), and sepsis (OR: 1.7; 95% CI 1.4-2.02) compared to White patients. CONCLUSIONS: Racial disparities exist among IBD patients undergoing surgery. Black, Hispanic and Asian IBD patients experience major disparities in post-operative complications, readmissions and LOS, respectively, when compared to White patients with IBD. Future research is needed to better understand the mechanisms of these disparities including evaluation of social determinants of health.

Development and characteristics of a multidisciplinary colorectal cancer clinic.

BACKGROUND: Multidisciplinary cancer clinics deliver streamlined care and facilitate collaboration between specialties. We described patient volume and specialty service utilization, including surgery, of a multidisciplinary colorectal cancer clinic established at a tertiary care academic institution. METHODS: We conducted a retrospective observational cohort study of adult patients with colorectal adenocarcinoma from 2012 to 2017. We performed a descriptive analysis of patient volume, percentage of rectal cancer patients, and the number of patients who saw and received surgery, chemotherapy, and radiation each year. RESULTS: Over 5 years, 1711 patients were served at the multidisciplinary clinic. Patient volume increased 37%, from n = 228 (annualized) to n = 312. The percentage of rectal cancer patients increased from 29% in 2013 to 42% in 2017. The highest rate of utilization was for surgery; 792 (46%) patients had surgery at the multidisciplinary clinic institution, and 510 (30%) received chemotherapy there. Out of 635 rectal cancer patients, 114 (18%) received radiation there. CONCLUSIONS: Over the five-year experience of a colorectal cancer-focused multidisciplinary clinic, overall patient volume increased by 37%. Over the study period, 63% of patients seen at the multidisciplinary clinic ultimately received at least one treatment modality at the clinic institution. Overall, the clinic's establishment resulted in the increased referral of complex patients.

Characteristics of Patients Seeking Second Opinions at a Multidisciplinary Colorectal Cancer Clinic.

BACKGROUND: Patients seeking second opinions are a challenge for the colorectal cancer provider because of complexity, failed therapeutic relationship with another provider, need for reassurance, and desire for exploration of treatment options. OBJECTIVE: The purpose of this study was to describe the patient and treatment characteristics of patients seeking initial and second opinions in colorectal cancer care at a multidisciplinary colorectal cancer clinic. DESIGN: This was a retrospective cohort study. SETTINGS: A prospectively collected clinical registry of a multidisciplinary colorectal cancer clinic was included. PATIENTS: The study included patients with colon or rectal cancer seen from 2012 to 2017. MAIN OUTCOME MEASURES: Data were analyzed for initial versus second opinion and demographic and clinical characteristics. RESULTS: Of 1711 patients with colorectal cancer, 1008 (58.9%) sought an initial opinion and 700 (40.9%) sought a second opinion. As compared with initial-opinion patients, second-opinion patients were more likely to have stage IV disease (OR = 1.94 (95% CI, 1.47-2.58)), recurrent disease (OR = 1.67 (95% CI, 1.13-2.46)), and be ages 40 to 49 years (OR = 1.47 (95% CI, 1.02-2.12)). Initial- and second-opinion cohorts were similar in terms of sex, race, and proportion of colon versus rectal cancer. Among second-opinion patients, 246 (35%) transitioned their care to the multidisciplinary colorectal cancer clinic. LIMITATIONS: We were unable to capture the final treatment plan for those patients who did not transfer care to the multidisciplinary colorectal cancer clinic. CONCLUSIONS: Patients seeking a second opinion represent a unique subset of patients with colorectal cancer. In general, they are younger and more likely to have stage IV or recurrent disease than patients seeking an initial opinion. Although transfer of care to a multidisciplinary colorectal cancer clinic after second opinion is lower than for initial consultations, multidisciplinary colorectal cancer clinics provide an important role for patients with complex disease characteristics and treatment needs. See Video Abstract at http://links.lww.com/DCR/B192. CARACTERíSTICAS DE LOS PACIENTES QUE BUSCAN UNA SEGUNDA OPINIóN EN CLíNICAS MULTIDISCIPLINARIAS ESPECIALIZADAS EN CáNCER COLORECTAL: Los pacientes que buscan una segunda opinión son un desafío para el médico que trata el cáncer colorrectal debido a la complejidad de la situación, a la relación terapéutica fallida con otro especialista, a la necesidad de tranquilidad y el deseo de explorar otras opciones del tratamiento.El describir las características y el tratamiento de los pacientes que buscan opiniones iniciales y secundarias en la atención del cáncer colorrectal en una clínica especializada de manera multidisciplinaria en cáncer colorrectal.Este es un estudio de cohortes retrospectivo.Registro clínico de casos obtenidos prospectivamente en una clínica especializada de manera multidisciplinaria en cáncer colorrectal.Todos aquellos pacientes con cáncer de colon o recto examinados entre 2012-2017.Se analizaron los datos obtenidos en la opinión inicial y se compararon con la segunda opinión, se revisaron tanto sus características demográficas como clínicas.De 1711 pacientes con cáncer colorrectal, 1008 (58.9%) buscaron una opinión inicial, 700 (40.9%) buscaron una segunda opinión. En comparación con los pacientes de opinión inicial, los pacientes de segunda opinión presentaron más probabilidades de tener enfermedad en estadio IV (OR 1.94, IC 95% 1.47-2.58), enfermedad recurrente (OR 1.67, IC 95% 1.13-2.46) y tener edades entre 40 y 49 (O 1.47, IC 95% 1.02-2.12). Las cohortes iniciales y de segunda opinión fueron similares en términos de género, raza y proporción del cáncer de colon versus cáncer de recto. Entre los pacientes de segunda opinión, 246 (35%) transfirieron su tratamiento hacia una clínica multidisplinaria especializada en cáncer colorrectal.No se obtuvieron los planes del tratamiento final de aquellos pacientes que no transfirieron sus cuidados hacia una la clínica especializada en cáncer colorrectal.Los pacientes que buscan una segunda opinión representan un subconjunto único de personas con cáncer colorrectal. En general, son más jóvenes y tienen más probabilidades de tener enfermedad en estadio IV o recurrente, con relación a aquellos pacientes que buscan una opinión inicial. Aunque la transferencia de los cuidados hacia una clínica multidisciplinaria especializada en cáncer colorrectal después de una segunda opinión es menor que para las consultas iniciales. Las clínicas multidisciplinarias especializadas en cáncer colorrectal juegan un papel importante con los pacientes que tienen características complejas de enfermedad y necesidades particulares en el tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B192. (Traducción-Dr Xavier Delgadillo).

Use of Accelerated Induction Strategy of Infliximab for Ulcerative Colitis in Hospitalized Patients at a Tertiary Care Center.

BACKGROUND: Infliximab can prevent colectomy in patients hospitalized with acute severe ulcerative colitis (ASUC). In cases of ASUC, fecal losses of infliximab may lead to low drug levels and reduced efficacy. AIM: To determine 90-day colectomy risk and postoperative complications in patients receiving single-dose and accelerated induction of infliximab for ASUC. METHODS: We conducted a retrospective review of patients hospitalized with ASUC requiring infliximab therapy between 2013 and 2017 at the University of Michigan. Patients were excluded if they had an enteric infection, received an anti-TNF previously, or received cyclosporine during the same admission. The primary outcome was colectomy within 90 days of admission. Patients receiving single-dose induction infliximab were compared to those receiving accelerated rescue induction with two doses of infliximab prior to day 14. Administration of accelerated induction was guided by a protocol, suggesting administering a second dose of infliximab to those with only a partial response in CRP 3 days after the initial dose. Postoperative outcomes including 30-day readmission rates and complications were compared using descriptive statistics. RESULTS: From 2013 to 2017, 66 patients with ASUC met our criteria. Thirty-three received accelerated induction (50.0%). The colectomy rate in the accelerated induction group was 30.3% versus 24.2% in the single-dose induction group (p = 0.58). There was no detected difference in postoperative outcomes between the accelerated and single-dose rescue induction. CONCLUSIONS: In this retrospective review, 69.7% of those failing to respond to single-dose infliximab were able to avoid colectomy with an accelerated rescue induction strategy without worsening postoperative outcomes. Larger studies of accelerated dosing infliximab are needed.

Completeness of operative reports for rectal cancer surgery.

INTRODUCTION: Synoptic operative reporting has been shown to improve completeness and consistency in surgical documentation. We sought to determine whether operative reports contain the key elements recommended by the National Accreditation Program for Rectal Cancer. METHODS: Rectal cancer operative reports from June-December 2018 were submitted from ten hospitals in Michigan. These reports were analyzed to identify key elements in the synoptic operative template and assessed for completeness. RESULTS: In total, 110 operative reports were reviewed. Thirty-one (28%) reports contained all 24 elements; all of these reports used a synoptic template. Overall, 62 (56%) reports used a synoptic template and 48 (44%) did not. Using a synoptic template significantly improved documentation, as these reports contained 92% of required elements, compared to 39% for narrative reports (p < 0.001). CONCLUSIONS/DISCUSSION: Narrative operative reports inconsistently document rectal cancer resection. This study provides evidence that synoptic reporting will improve quality of documentation for rectal cancer surgery.

Rectal cancer sub-clones respond differentially to neoadjuvant therapy.

Treatment of locally advanced rectal cancer includes chemotherapy, radiation, and surgery but patient responses to neoadjuvant treatment are variable. We have shown that rectal tumors are comprised of multiple genetically distinct sub-clones. Unique sub-clones within tumors may harbor mutations which contribute to inter-patient variation in response to neoadjuvant chemoradiotherapy (nCRT). Analysis of the influence of nCRT on the extent and nature of intra-tumoral genetic heterogeneity in rectal cancer may provide insights into mechanisms of resistance. Locally advanced rectal cancer patients underwent pre-treatment biopsies. At the time of surgery, tissue from the treated tumor was obtained and analyzed. Pre- and post-treatment specimens were subjected to whole exome and confirmatory deep sequencing for somatic mutations. Copy number variation was assessed using OncoScan SNP arrays. Genomic data were analyzed using PyClone to identify sub-clonal tumor population following nCRT. Alterations that persisted or were enriched in the post-treatment tumor specimen following nCRT were defined for each patient. Thirty-two samples were obtained from ten patients. PyClone identified 2 to 10 genetic sub-clones per tumor. Substantial changes in the proportions of individual sub-clones in pre- versus post-treatment tumor material were found in all patients. Resistant sub-clones recurrently contained mutations in TP53, APC, ABCA13, MUC16, and THSD4. Recurrent copy number variation was observed across multiple chromosome regions after nCRT. Pathway analysis including variant alleles and copy number changes associated with resistant sub-clones revealed significantly altered pathways, especially those linked to the APC and TP53 genes, which were the two most frequently mutated genes. Intra-tumoral heterogeneity is evident in pre-treatment rectal cancer. Following treatment, sub-clonal populations are selectively modified and enrichment of a subset of pre-treatment sub-clones is seen. Further studies are needed to define recurrent alterations at diagnosis that may contribute to resistance to nCRT.