Drug repurposing of ilepcimide that ameliorates experimental autoimmune encephalomyelitis via restricting inflammatory response and oxidative stress.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS) that remains incurable. Herein, we demonstrated that ilepcimide (Antiepilepsirine), an antiepileptic drug used for decades, protects mice from experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Our studies found that ilepcimide treatment effectively ameliorates demyelination, blood-brain barrier leakage and infiltration of CD4+ and CD8+ T cells in EAE mice. On the one hand, ilepcimide can inhibit dihydroorotate dehydrogenase (DHODH), an important therapeutic target for MS. Computer molecular docking, thermal shift and fluorescence quenching assay demonstrated the directly interaction between ilepcimide and DHODH. Accordingly, ilepcimide observably repressed T cell proliferation in mixed lymphocyte reaction (MLR) assay and concanavalin A (Con-A) model in a DHODH-dependent manner. On the other hand, ilepcimide exhibited neuroprotective effect possibly through activating NRF2 antioxidant pathway in mouse neural crest-derived Neuro2a cells. Collectively, our findings have revealed the therapeutic potential of ilepcimide in EAE mouse model via restricting inflammatory response and oxidative stress, offering a potential opportunity for repurposing existing drug ilepcimide for MS therapy.

How Far Is Too Far? Cost-Effectiveness Analysis of Regionalized Rectal Cancer Surgery.

BACKGROUND: Regionalized rectal cancer surgery may decrease postoperative and long-term cancer-related mortality. However, the regionalization of care may be an undue burden on patients. OBJECTIVE: This study aimed to assess the cost-effectiveness of regionalized rectal cancer surgery. DESIGN: Tree-based decision analysis. PATIENTS: Patients with stage II/III rectal cancer anatomically suitable for low anterior resection were included. SETTING: Rectal cancer surgery performed at a high-volume regional center rather than the closest hospital available. MAIN OUTCOME MEASURES: Incremental costs ($) and effectiveness (quality-adjusted life year) reflected a societal perspective and were time-discounted at 3%. Costs and benefits were combined to produce the incremental cost-effectiveness ratio ($ per quality-adjusted life year). Multivariable probabilistic sensitivity analysis modeled uncertainty in probabilities, costs, and effectiveness. RESULTS: Regionalized surgery economically dominated local surgery. Regionalized rectal cancer surgery was both less expensive on average ($50,406 versus $65,430 in present-day costs) and produced better long-term outcomes (10.36 versus 9.51 quality-adjusted life years). The total costs and inconvenience of traveling to a regional high-volume center would need to exceed $15,024 per patient to achieve economic breakeven alone or $112,476 per patient to satisfy conventional cost-effectiveness standards. These results were robust on sensitivity analysis and maintained in 94.6% of scenario testing. LIMITATIONS: Decision analysis models are limited to policy level rather than individualized decision-making. CONCLUSIONS: Regionalized rectal cancer surgery improves clinical outcomes and reduces total societal costs compared to local surgical care. Prescriptive measures and patient inducements may be needed to expand the role of regionalized surgery for rectal cancer. See Video Abstract at http://links.lww.com/DCR/C83 . QU TAN LEJOS ES DEMASIADO LEJOS ANLISIS DE COSTOEFECTIVIDAD DE LA CIRUGA DE CNCER DE RECTO REGIONALIZADO: ANTECEDENTES:La cirugía de cáncer de recto regionalizado puede disminuir la mortalidad posoperatoria y a largo plazo relacionada con el cáncer. Sin embargo, la regionalización de la atención puede ser una carga indebida para los pacientes.OBJETIVO:Evaluar la rentabilidad de la cirugía oncológica de recto regionalizada.DISEÑO:Análisis de decisiones basado en árboles.PACIENTES:Pacientes con cáncer de recto en estadio II/III anatómicamente aptos para resección anterior baja.AJUSTE:Cirugía de cáncer rectal realizada en un centro regional de alto volumen en lugar del hospital más cercano disponible.PRINCIPALES MEDIDAS DE RESULTADO:Los costos incrementales ($) y la efectividad (años de vida ajustados por calidad) reflejaron una perspectiva social y se descontaron en el tiempo al 3%. Los costos y los beneficios se combinaron para producir la relación costo-efectividad incremental ($ por año de vida ajustado por calidad). El análisis de sensibilidad probabilístico multivariable modeló la incertidumbre en las probabilidades, los costos y la efectividad.RESULTADOS:La cirugía regionalizada predominó económicamente la cirugía local. La cirugía de cáncer de recto regionalizado fue menos costosa en promedio ($50 406 versus $65 430 en costos actuales) y produjo mejores resultados a largo plazo (10,36 versus 9,51 años de vida ajustados por calidad). Los costos totales y la inconveniencia de viajar a un centro regional de alto volumen necesitarían superar los $15,024 por paciente para alcanzar el punto de equilibrio económico o $112,476 por paciente para satisfacer los estándares convencionales de rentabilidad. Estos resultados fueron sólidos en el análisis de sensibilidad y se mantuvieron en el 94,6% de las pruebas de escenarios.LIMITACIONES:Los modelos de análisis de decisiones se limitan al nivel de políticas en lugar de la toma de decisiones individualizada.CONCLUSIONES:La cirugía de cáncer de recto regionalizada mejora los resultados clínicos y reduce los costos sociales totales en comparación con la atención quirúrgica local. Es posible que se necesiten medidas prescriptivas e incentivos para los pacientes a fin de ampliar el papel de la cirugía regionalizada para el cáncer de recto. Consulte Video Resumen en http://links.lww.com/DCR/C83 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Impact of Total Neoadjuvant Therapy on Postoperative Outcomes After Proctectomy for Rectal Cancer.

BACKGROUND: Total neoadjuvant therapy is an alternative to neoadjuvant chemoradiation alone for rectal cancer and has the benefits of more completion of planned therapy, increased downstaging, earlier treatment of micrometastases, and assessment of chemosensitivity; however, it may increase surgical complications, especially with increased radiation-to-surgery interval. OBJECTIVE: The study aimed to determine the impact of total neoadjuvant therapy on postoperative complications compared with neoadjuvant chemoradiation alone. DESIGN: Retrospective cohort study. SETTINGS: Single tertiary referral center. PATIENTS: The patient included was a stage II/III rectal cancer patient who underwent total neoadjuvant therapy or long-course neoadjuvant chemoradiation followed by surgical resection from 2018-2020. MAIN OUTCOME MEASURES: The main outcome measures included severe postoperative complications (Clavien-Dindo grade ≥3). RESULTS: Of 181 patients, 86 (47.5%) underwent total neoadjuvant therapy and 95 (52.5%) underwent neoadjuvant chemoradiation. There was no difference in severe postoperative complications or any complications. There was also no difference in the rate of complete total mesorectal excision or negative circumferential margin. Total neoadjuvant therapy had a mean operative time of 355.5 minutes and estimated blood loss of 263.6 mL compared with 326.7 minutes and 297.5 mL in the neoadjuvant chemoradiation group. Total neoadjuvant therapy patients had a lower mean lymph node yield than neoadjuvant chemoradiation patients. On multivariable analysis, total neoadjuvant therapy was associated with increased operative time (OR, 1.19; p < 0.001) and estimated blood loss (OR, 1.22; p < 0.001) and decreased lymph node yield (OR, 0.67; p < 0.001). There was no difference in severe complications or any complications. LIMITATIONS: Selection bias uncontrolled by modeling. CONCLUSIONS: We found no difference in risk of postoperative complications between patients who received total neoadjuvant therapy vs neoadjuvant chemoradiation. Total neoadjuvant therapy patients had longer operations and greater estimated blood loss. This may be a reflection of increased operative difficulty because of increased radiation-to-surgery interval and/or the effects of chemotherapy; however, the absolute differences were small and, therefore, should be interpreted cautiously. See Video Abstract at http://links.lww.com/DCR/C44 . IMPACTO DE LA TERAPIA NEOADYUVANTE TOTAL EN LOS RESULTADOS POSOPERATORIOS DESPUS DE UNA PROCTECTOMA POR CNCER DE RECTO: ANTECEDENTES:La terapia neoadyuvante total es una alternativa a la quimiorradiación neoadyuvante sola para el cáncer de recto y tiene los beneficios de una mayor finalización de la terapia planificada, mayor reducción del estadiage, tratamiento más temprano de las micrometástasis y evaluación de la quimiosensibilidad; sin embargo, puede aumentar las complicaciones quirúrgicas, especialmente con un mayor intervalo entre la radiación y la cirugía.OBJETIVO:Determinar el impacto de la terapia neoadyuvante total sobre las complicaciones posoperatorias en comparación con la quimiorradiación neoadyuvante sola.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:Centro único de referencia terciario.PACIENTES:Paciente con cáncer de recto en estadio II/III que se sometieron a terapia neoadyuvante total o quimiorradiación neoadyuvante de larga duración seguida de resección quirúrgica entre 2018 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:Complicaciones postoperatorias graves (grado de Clavien-Dindo ≥3).RESULTADOS:De 181 pacientes, 86 (47,5%) se sometieron a terapia neoadyuvante total y 95 (52,5%) se sometieron a quimiorradioterapia neoadyuvante. No hubo diferencia en las complicaciones postoperatorias graves o cualquier otra complicación. Tampoco hubo diferencia en la tasa de escisión mesorrectal total completa o margen circunferencial negativo. La terapia neoadyuvante total tuvo un tiempo operatorio promedio de 355,5 minutos y una pérdida de sangre estimada de 263,6 ml en comparación con 326,7 minutos y 297,5 ml en el grupo de quimiorradiación neoadyuvante. Los pacientes con terapia neoadyuvante total tuvieron una media de ganglios linfáticos más bajo en comparación con los pacientes con quimiorradioterapia neoadyuvante. En el análisis multivariable, la terapia neoadyuvante total se asoció con un mayor tiempo operatorio (OR = 1,19, p < 0,001) y pérdida de sangre estimada (OR = 1,22, p < 0,001) y menor cantidad los ganglios linfáticos (OR = 0,67, p < 0,001). No hubo diferencia en las complicaciones graves o cualquier complicación.LIMITACIONES:Sesgo de selección no controlado por modelado.CONCLUSIONES:No encontramos diferencias en el riesgo de complicaciones postoperatorias entre los pacientes que recibieron terapia neoadyuvante total versus quimiorradiación neoadyuvante. Los pacientes con terapia neoadyuvante total tuvieron operaciones más prolongadas y una mayor pérdida de sangre estimada. Esto puede ser un reflejo de una mayor dificultad quirúrgica como resultado de un mayor intervalo entre la radiación y la cirugía y/o los efectos de la quimioterapia; sin embargo, las diferencias absolutas fueron pequeñas y, por lo tanto, deben interpretarse con cautela. Consulte Video Resumen en http://links.lww.com/DCR/C44 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Could meeting the standards of the National Accreditation Program for Rectal Cancer in the National Cancer Database improve patient outcomes?

AIM: The National Accreditation Program for Rectal Cancer (NAPRC) was developed to improve rectal cancer patient outcomes in the United States. The NAPRC consists of a set of process and outcome measures that hospitals must meet in order to be accredited. We aimed to assess the potential of the NAPRC by determining whether achievement of the process measures correlates with improved survival. METHODS: The National Cancer Database was used to identify patients undergoing curative proctectomy for non-metastatic rectal cancer from 2010 to 2014. NAPRC process measures identified in the National Cancer Database included clinical staging completion, treatment starting <60 days from diagnosis, carcinoembryonic antigen level measured prior to treatment, tumour regression grading and margin assessment. RESULTS: There were 48 669 patients identified with a mean age of 62 ± 12.9 years and 61.3% of patients were men. The process measure completed most often was assessment of proximal and distal margins (98.4%) and the measure completed least often was the serum carcinoembryonic antigen level prior to treatment (63.8%). All six process measures were completed in 23.6% of patients. After controlling for age, gender, comorbidities, annual facility resection volume, race and pathological stage, completion of all process measures was associated with a statistically significant mortality decrease (Cox hazard ratio 0.88, 95% CI 0.81-0.94, P < 0.001). CONCLUSION: Participating institutions provided complete datasets for all six process measures in less than a quarter of patients. Compliance with all process measures was associated with a significant mortality reduction. Improved adoption of NAPRC process measures could therefore result in improved survival rates for rectal cancer in the United States.

Is robotic utilization associated with increased minimally invasive colorectal surgery rates? Surgeon-level evidence.

BACKGROUND: It is unclear whether robotic utilization has increased overall minimally invasive colorectal surgery rates or if robotics is being adopted instead of laparoscopy. The goal was to evaluate whether increasing robotic surgery utilization is associated with increased rates of overall colorectal minimally invasive surgery. METHODS: The Statewide Planning and Research Cooperative System (New York) was used to identify patients undergoing elective colectomy or proctectomy from 2009 to 2015. Individual surgeons were categorized as having increasing or non-increasing robotic utilization (IRU or non-IRU, respectively) based on the annual increase in the proportion of robotic surgery performed. The odds of surgical approach across the study period were evaluated with multinomial regression. RESULTS: Among 72,813 resections from 2009 to 2015, minimally invasive-surgery increased (47-61%, p < 0.0001). For colectomy, overall minimally invasive-surgery rates increased (54-66%, p < 0.0001), laparoscopic remained stable (53-54%), and robotics increased (1-12%). For proctectomy, overall minimally invasive-surgery rates increased (22-43%, p < 0.0001), laparoscopic remained stable (20-21%), and robotics increased (2-22%). Over the study period, 2487 surgeons performed colectomies. Among 156 surgeons with IRU for colectomies, robotics increased (2-29%), while laparoscopy decreased (67-44%), and open surgery decreased (31-27%). Overall, surgeons with IRU performed minimally invasive colectomies 73% of the time in 2015 versus 69% in 2009. Over the study period, 1131 surgeons performed proctectomies. Among 94 surgeons with IRU for proctectomies, robotics increased (3-42%), while laparoscopy decreased (25-15%), and open surgery decreased (73-44%). Overall, surgeons with IRU performed minimally invasive proctectomy 56% of the time in 2015 versus 27% in 2009. Patients in the latter study period had 57% greater odds of undergoing robotic surgery. CONCLUSIONS: Overall, minimally invasive colorectal resections increased from 2009 to 2015 largely due to increasing robotic utilization, particularly for proctectomies.

Variation in Adequate Lymph Node Yield for Gastric, Lung, and Bladder Cancer: Attributable to the Surgeon, Pathologist, or Hospital?

BACKGROUND: The Commission on Cancer recently released quality-of-care measures regarding adequate lymphadenectomy for colon, gastric, lung, and bladder cancer. There is currently little information regarding variation in adequate lymph node yield (ALNY) for gastric, lung, and bladder cancer. METHODS: The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for stage I-III gastric, stage I-II lung, and stage II-III bladder cancer resections from 2004 to 2014. Hierarchical models assessed factors associated with ALNY (gastric ≥ 15; lung ≥ 10; bladder ≥ 2). Additionally, the proportions of variation attributable to surgeons, pathologists, and hospitals were estimated among Medicare patients. RESULTS: Among 3716 gastric, 18,328 lung, and 1512 bladder cancer resections, there were low rates of ALNY (gastric = 53%, lung = 36%, bladder = 67%). When comparing 2004-2006 and 2012-2014, there was significant improvement in ALNY for gastric cancer (39% vs. 68%), but more modest improvement for lung (33% vs. 38%) and bladder (65% vs. 71%) cancer. Large provider-level variation existed for each organ system. After controlling for patient-level factors/variation, the majority of variation was attributable to hospitals (gastric: surgeon = 4%, pathologist = 2.8%, hospital = 40%; lung: surgeon = 13.8%, pathologist = 1.5%, hospital = 18.3%) for gastric and lung cancer. For bladder cancer, most of the variation was attributable to pathologists (surgeon = 3.3%, pathologist = 10.5%, hospital = 6.2%). CONCLUSIONS: ALNY rates are low for gastric, lung, and bladder cancer, with only modest improvement over time for lung and bladder cancer. Given that the proportion of variation attributable to the surgeon, pathologist, and hospital is different for each organ system, future quality improvement initiatives should target the underlying causes, which vary by individual organ system.

Centralizing Rectal Cancer Surgery: What Is the Impact of Travel on Patients?

BACKGROUND: It is unclear what impact centralizing rectal cancer surgery may have on travel burden for patients. OBJECTIVE: This study aimed to determine the impact of centralizing rectal cancer surgery to high-volume centers on patient travel distance. DESIGN: This is a population-based study. SETTINGS: The New York State Cancer Registry and Statewide Planning and Research Cooperative System were queried for patients with rectal cancer undergoing proctectomy. PATIENTS: Patients with stage I to III rectal cancer who underwent surgical resection between 2004 and 2014 were included. MAIN OUTCOME MEASURES: The outcome of interest was travel distance calculated as the straight-line distance between the centroid of the patient residence zip code and the hospital zip code. Mean distance was compared by using the Student t test. RESULTS: A total of 5860 patients met inclusion criteria. The total number of hospitals performing proctectomies for rectal cancer decreased between 2004 and 2014. The average number of proctectomies performed at high-volume centers (20+ resections/year) increased from 16.6 to 24.4 during this time. The average number of miles traveled by patients was 12.1 miles in 2004, and this increased to 15.4 in 2014. If proctectomies were centralized to high-volume centers, there would be 11 facilities. The mean distance traveled would be 24.5 miles. LIMITATIONS: This study is subject to the limitations of an administrative data set. There are no patient preference or referral data. CONCLUSIONS: The number of hospitals performing rectal cancer resections in New York State is decreasing and volume by center is increasing. There was a statistically significant difference in the mean distance traveled by patients over time. If rectal cancer resections were centralized to high-volume centers, the mean travel distance would increase by 9.5 miles. There would be a 321% increase in the number of patients having to travel 50+ miles for surgery. Any plan for centralization in New York State will require careful planning to avoid placing undue travel burden on patients. See Video Abstract at http://links.lww.com/DCR/B138. CENTRALIZACIÓN DE LA CIRUGÍA DE CÁNCER RECTAL: ¿CUÁL ES EL IMPACTO DEL VIAJE PARA LOS PACIENTES?: No está claro qué impacto puede tener la centralización de la cirugía de cáncer rectal en la carga de viaje para los pacientes.Determinar el impacto de centralizar la cirugía de cáncer rectal en centros de alto volumen sobre la distancia de viaje del paciente.Este es un estudio basado en cohorte poblacional.El Registro de Cáncer del Estado de Nueva York y el Sistema Cooperativo de Planificación e Investigación Estatal fueron consultados para pacientes con cáncer rectal sometidos a proctectomía.Pacientes con cáncer rectal en estadio I-III que se sometieron a resección quirúrgica entre 2004-2014.El resultado de interés fue la distancia de viaje calculada como la distancia en línea recta entre el centroide de la residencia del paciente y el código postal del hospital. La distancia media se comparó mediante la prueba t de Student.Un total de 5,860 pacientes cumplieron los criterios de inclusión. El número total de hospitales que realizaron proctectomías para cáncer rectal disminuyó entre 2004-2014. El número promedio de proctectomías realizadas en centros de alto volumen (más de 20 resecciones/año) aumentó de 16.6 a 24.4 durante este tiempo. El número promedio de millas recorridas por los pacientes fue de 12.1 millas en 2004 y esto aumentó a 15.4 en 2014. Si las proctectomías se centralizaran en centros de alto volumen, habría 11 instalaciones. La distancia media recorrida sería de 24.5 millas.Limitaciones inherentes a un conjunto de datos administrativos. No existen datos sobre preferencia del paciente o sobre referencia de los mismos.El número de hospitales que realizan resecciones de cáncer rectal en Nueva York está disminuyendo y el volumen por centro está aumentando. Hubo una diferencia estadísticamente significativa en la distancia media recorrida por los pacientes a lo largo del tiempo. Si las resecciones por cáncer rectal se centralizaran en centros de gran volumen, la distancia media de viaje aumentaría 9.5 millas. Habría un aumento del 321% en el número de pacientes que tienen que viajar más de 50 millas para la cirugía. Cualquier plan de centralización en Nueva York requerirá una planificación cuidadosa para evitar imponer una carga de viaje excesiva a los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B138.

A Population-Based Study of 90-Day Hospital Cost and Utilization Associated With Robotic Surgery in Colon and Rectal Cancer.

BACKGROUND: The role of robotic surgery in colorectal cancer remains contentious with most data arising from small, single-institution studies. METHODS: Stage I-III colorectal cancer resections from 2008 to 2014 were identified in New York State. Propensity score-adjusted negative binomial models were used to compare cost and utilization between robotic, laparoscopic, and open resections. RESULTS: A total of 12,218 patients were identified. For colectomy, the robotic-to-open conversion rate was 3%, and the laparoscopic-to-open conversion rate was 13%. For rectal resection, the robotic-to-open conversion rate was 7% and the laparoscopic-to-open conversion rate was 32%. In intention-to-treat analysis, there was no significant difference in cost across the surgical approaches, both in overall and stratified analyses. Both laparoscopic and robotic approaches were associated with decreased 90-d hospital utilization compared with open surgery in intention-to-treat analyses. CONCLUSIONS: Robotic and laparoscopic colorectal cancer resections were not associated with a hospital cost benefit after 90 d compared with open but were associated with decreased hospital utilization. Conversion to open resection was common, and efforts should be made to prevent them. Future research should continue to measure how robotic and laparoscopic approaches can add value to the health care system.

Complications and Survivorship Trends After Primary Debulking Surgery for Ovarian Cancer.

BACKGROUND: We examined factors associated with postoperative complications, 1-year overall and cancer-specific survival after epithelial ovarian cancer (EOC) diagnosis. METHODS: Patients who underwent surgery for EOC between 2004 and 2013 were included. Multivariable models analyzed postoperative complications, overall survival, and cancer-specific survival. RESULTS: Among 5223 patients, surgical complications were common. Postoperative complications correlated with increased odds of overall and disease-specific survival at 1 y. Receipt of chemotherapy was similar among women with and without postoperative complications and was independently associated with a reduction in the hazard of overall and disease-specific death at 1-year. Extensive pelvic and upper abdomen surgery resulted in 2.26 times the odds of postoperative complication, but was associated with longer 1-year overall 0.53 (0.35, 0.82) and disease-specific survival 0.54 (0.34, 0.85). CONCLUSIONS: Although extent of surgery was associated with complications, the survival benefit from comprehensive surgery offset the risk. Tailored surgical treatment for women with EOC may improve outcomes.

Postoperative Mortality After Nonelective Surgery for Inflammatory Bowel Disease Patients in the Era of Biologics.

OBJECTIVE: The aim of the study was to analyze recent trends in the rate of nonelective surgery and corresponding mortality for inflammatory bowel disease (IBD) patients since the rise of biologic use. BACKGROUND: Modern biologic therapy has improved outcomes for IBD, but little is known about the impact on mortality rates after nonelective surgery. METHODS: New York's Statewide Planning & Research Cooperative System was queried for hospital admissions for ulcerative colitis (UC) with concurrent colectomy and Crohn disease (CD) with concurrent small bowel resection or colectomy from 2000 to 2013. Mixed-effects analyses assessed patient, surgeon, and hospital-level factors and hospital-level variation associated with 30-day mortality after nonelective surgery. RESULTS: Between 2000 to 2006 and 2007 to 2013, the number of unscheduled IBD-related admissions increased by 50% for UC and 41% for CD, but no change in the proportion of nonelective surgery cases was observed (UC=38% vs 38%; CD=45% vs 42%) among 15,837 intestinal resections (UC=5,297; CD=10,540). Nonelective surgery mortality rates between 2000 to 2006 and 2007 to 2013 were high and increased for UC (10.2% vs 15%) but decreased for CD (3.3% vs 2.2%). Nonelective surgery in 2007 to 2013 was associated with an 82% increased risk of 30-day mortality in UC cases (odds ratio: 1.82; confidence interval: 1.19-2.62). After controlling for patient-level factors, large hospital-level variation was observed with 23-fold difference in mortality for both UC and CD. CONCLUSIONS: Although nonelective IBD surgery rates have remained stable, associated 30-day mortality for UC has doubled in recent years despite advances in medical management. Current clinical decision-making and care pathways must be further evaluated to improve outcomes in this high-risk population.

Surgeon, Hospital, and Geographic Variation in Minimally Invasive Colectomy.

OBJECTIVE: To identify sources of variation in the use of minimally invasive surgery (MIS) for colectomy. BACKGROUND: MIS is associated with decreased analgesic use, shorter length of stay, and faster postoperative recovery. This study identified factors explaining variation in MIS use for colectomy. METHODS: The Statewide Planning and Research Cooperative System was queried for scheduled admissions in which a colectomy was performed for neoplastic, diverticular, or inflammatory bowel disease between 2008 and 2015. Mixed-effects analyses were performed assessing surgeon, hospital, and geographic variation and factors associated with an MIS approach. RESULTS: Among 45,714 colectomies, 68.1% were performed using an MIS approach. Wide variation in the rate of MIS was present across 1253 surgeons (median 50%, interquartile range 10.9%-84.2%, range 0.3%-99.7%). Calculating intraclass correlation coefficients after controlling for case-mix, 62.8% of the total variation in MIS usage was attributable to surgeon variation compared with 28.5% attributable to patient variation, 7% attributable to hospital variation, and 1.6% attributable to geographic variation. Surgeon-years in practice since residency/fellowship completion explained 19.2% of the surgeon variation, surgeon volume explained 5.2%, hospital factors explained 0.1%, and patient factors explained 0%. CONCLUSIONS: Wide surgeon variation exists regarding an MIS approach for colectomy, and most of the total variation is attributable to individual surgeon practices-much of which is related to year of graduation. As increasing surgeon age is inversely proportional to the rate of MIS, patient referral and/or providing tailored training to older surgeons may be constructive targets in increasing the use of MIS and reducing healthcare utilization.

Treatments for Stage IV Colon Cancer and Overall Survival.

BACKGROUND: The role of primary tumor resection (PTR) for asymptomatic stage IV colon cancer with unresectable metastases remains unclear. Increasingly there has been a trend away from resection. The aim of this study was to examine trends in the treatment of stage IV colon cancers, impact of different treatments on long-term mortality, and factors associated with receipt of postoperative chemotherapy. METHODS: The 2006-2012 National Cancer Data Base was queried for stage IV colon cancer patients. Treatments were grouped into PTR and chemotherapy, PTR only, chemotherapy only, and no treatment. A descriptive analysis was performed examining patient and hospital characteristics associated with different treatments. A Cox regression analysis was used to assess the adjusted effect of different treatments on long-term survival. A multivariable logistic regression was used to examine factors associated with postoperative chemotherapy. RESULTS: Of 31,310 patients, who met inclusion criteria, 22% of the patients underwent PTR and chemotherapy, 37.5% received chemotherapy only, 11.9% underwent PTR, and 28.6% received no treatment. Patients who received no treatment had the highest hazard of death at 1, 3, and 5 y, followed by PTR only, and chemotherapy only compared with PTR combined with chemotherapy. Patients who were older and had more comorbidities were less likely to receive postoperative chemotherapy. CONCLUSIONS: Primary tumor resection in conjunction with postoperative chemotherapy among stage IV colon cancer patients with unresectable metastases was associated with a long-term survival benefit compared with other treatment options. Efforts should be made to increase the use of postoperative chemotherapy where feasible.

Nationwide Heterogeneity in Hospital-Specific Probabilities of Rectal Cancer Understaging and Its Effects on Outcomes.

BACKGROUND: Rectal cancer patients who are understaged may not be offered the highest quality treatment modalities, which are based on an accurate assessment of preoperative staging. The objective of this study was to evaluate heterogeneity in the probability of being understaged at Commission on Cancer hospitals in the United States and to assess how this variation affects outcomes. METHODS: The 2006-2013 National Cancer Data Base was queried for clinical stage I-III rectal cancer patients who underwent resection. The initial clinical stage was compared with the "gold standard," pathological stage. A Bayesian multilevel logistic regression model was used to characterize variation in hospital-specific probabilities of being understaged (clinical stage < pathologic stage). Separate analyses assessed the impact of being understaged on positive circumferential resection margins (CRM), receipt of adjuvant chemotherapy, and 5-year overall survival. RESULTS: Among 12,684 patients who did not receive neoadjuvant chemoradiation and treated at 1176 hospitals, 3044 (24%) were understaged. After patient level risk-adjustment, a 24-fold difference in the probability of being understaged was observed between hospitals (range 3-72%, median = 15%). Understaging was independently associated with positive CRM [odds ratio (OR) 1.59, 95% confidence interval (CI) 1.39, 1.92] and receipt of adjuvant chemotherapy (OR 14.22, 95% CI 13.55, 18.88). Despite an increase in the delivery of systemic therapy after surgical resection, understaging was associated with worse survival (hazard ratio = 1.61, 95% CI 1.48, 1.95). CONCLUSIONS: Deficiencies in high-quality rectal cancer management begin with incorrect clinical staging. The risk-adjusted probability of understaging varied widely between hospitals. This institutional failure to provide optimal oncological management at the start of care was associated with worse long-term survival.

Readmissions With Dehydration After Ileostomy Creation: Rethinking Risk Factors.

BACKGROUND: Twenty-nine percent of postileostomy discharges are readmitted, most commonly because of dehydration. However, there is a lack of detailed data specifically evaluating factors associated with readmission with dehydration. In addition, patients with a history of an ileostomy have often been excluded from previous studies and therefore represent a group of understudied ileostomates. OBJECTIVE: This study aimed to evaluate factors available at discharge associated with 30-day readmission for dehydration, rather than all-cause readmissions. DESIGN: This was a retrospective cohort study. SETTING: Study patients received ileostomies at a tertiary academic medical center from 2014 to 2016. PATIENTS: Patients with a preexisting ileostomy that was not recreated per the operative note were excluded, whereas those who received a new ileostomy were included. MAIN OUTCOME MEASURE: The primary outcome measured was 30-day readmission for dehydration as defined by objective clinical criteria. RESULTS: A total of 262 patients underwent ileostomy creation and were discharged alive. Twenty-five percent were ≥65 years of age, 53% were men, 14% had a history of ileostomy, 18% had a creatinine >1.0 on discharge, and 26% had high ileostomy output at any time during the index admission. Among all ileostomates, the all-cause readmission rate was 30%. Mean days to readmission for any cause was 8.5, whereas for dehydration it was 11.6 days. Of the readmissions, 37% were readmitted with a diagnosis of dehydration, and dehydration was the sole reason in 26%. Among those with dehydration, the most common length of stay was 2 days. In multivariable logistic regression, 30-day readmission with dehydration was associated with older age, male sex, history of an ileostomy, high ileostomy output during index admission, and a discharge creatinine >1.0. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: Ileostomy dehydration efforts have focused on new ileostomy patients; however, our data suggest that patients with a history of an ileostomy are actually at risk for readmission with dehydration. Further studies aimed at the reduction of readmission with dehydration after ileostomy are warranted and should include patients with a history of an ileostomy. See Video Abstract at http://links.lww.com/DCR/A643.

Trends in Surgeon-Level Utilization of Sacral Nerve Stimulator Implantation for Fecal Incontinence in New York State.

BACKGROUND: There is a paucity of real-world data regarding surgeon utilization of sacral nerve stimulation for fecal incontinence compared with anal sphincteroplasty. OBJECTIVE: This study aims to examine trends in sacral nerve stimulation use compared with sphincteroplasty for fecal incontinence and surgeon-level variation in progression to implantation of the pulse generator. DESIGN: This is a population-based study. PATIENTS: Patients with fecal incontinence between 2011 and 2014 in New York who underwent stage 1 of the sacral nerve stimulation procedure were selected. For the comparison with sphincteroplasty, patients with fecal incontinence who underwent anal sphincteroplasty between 2008 and 2014 were included. MAIN OUTCOME MEASURES: The main outcomes after sacral nerve stimulation generator placement were unplanned 30-day admission, emergency department visit within 30 days, revision or explant of leads or generator, and 30-day mortality. RESULTS: Six hundred twenty-one patients with fecal incontinence underwent a stage 1 procedure with 79.7% progressing to stage 2. There has been an increase in the number of sacral nerve stimulation cases per year as well as the number of surgeons performing the procedure. The rate of progression to stage 2 among patients treated by colorectal surgeons was 80.2% compared with 77.0% among those treated by noncolorectal surgeons. Among those who completed stage 2, there were 3 (0.5%) unplanned 30-day admissions, 24 (4.4%) emergency department visits within 30 days, and 0 mortalities within 30 days. Thirty-two (6.5%) patients had their leads or pulse generator revised or explanted. There was a significant decrease in annual sphincteroplasty cases and the number of providers performing the procedure starting in 2011. LIMITATIONS: We lacked data regarding patient and physician decision making and the severity of disease. CONCLUSIONS: Sacral nerve stimulation for fecal incontinence is increasing in popularity with an increasing number of surgeons utilizing sacral nerve stimulation for fecal incontinence rather than sphincteroplasty. See Video Abstract at http://links.lww.com/DCR/A450.

Poor compliance with adjuvant chemotherapy use associated with poorer survival in patients with rectal cancer: An NCDB analysis.

BACKGROUND: National Comprehensive Cancer Network treatment guidelines for patients with locally advanced rectal cancer include neoadjuvant chemoradiation followed by total mesorectal excision and adjuvant chemotherapy. The objective of the current study was to examine the rate of adjuvant chemotherapy and associated survival in patients with stage II/III rectal cancer. METHODS: The 2006 to 2011 National Cancer Data Base was queried for patients with AJCC clinical stage II/III rectal cancer who underwent neoadjuvant chemoradiation and surgical resection. A mixed effects multivariable logistic regression identified factors associated with the receipt of adjuvant chemotherapy. A mixed effects Cox proportional hazards model was used to estimate the adjusted effect of receiving adjuvant therapy on 5-year overall survival (OS). RESULTS: A total of 14,742 patients were included; 68% of the cohort did not receive adjuvant chemotherapy. When controlled for clinical stage of disease, patients who were aged >70 years, had a higher comorbidity score, and had a pathologic complete response had lower odds of receiving adjuvant therapy. There was a 22-fold difference in the risk-adjusted rate of adjuvant therapy use among hospitals (3.1%-67.7%). Adjuvant therapy was associated with increased 5-year OS when controlled for patient factors, stage of disease, and pathologic response (hazard ratio, 0.65; 95% confidence interval, 0.59-0.71). The greatest survival benefit was noted among patients who achieved a pathologic complete response (hazard ratio, 0.40; 95% confidence interval, 0.23-0.67). CONCLUSIONS: There is poor compliance to National Comprehensive Cancer Network guidelines for adjuvant chemotherapy in patients with locally advanced rectal cancer after neoadjuvant chemoradiation and surgery. Adjuvant therapy appears to be independently associated with improved OS regardless of stage of disease, pathologic response, and patient factors. The greatest survival benefit was observed in patients who were complete responders. Age and comorbidities were found to be significantly associated with nonreceipt of adjuvant therapy. Improved rehabilitation and physical conditioning may improve the odds of patients receiving adjuvant therapy. Cancer 2017;52-61. © 2016 American Cancer Society.

The impact of age on complications, survival, and cause of death following colon cancer surgery.

BACKGROUND: Given scarce data regarding the relationship among age, complications, and survival beyond the 30-day postoperative period for oncology patients in the United States, this study identified age-related differences in complications and the rate and cause of 1-year mortality following colon cancer surgery. METHODS: The NY State Cancer Registry and Statewide Planning and Research Cooperative System identified stage I-III colon cancer resections (2004-2011). Multivariable logistic regression and survival analyses assessed the relationship among age (<65, 65-74, ⩾75), complications, 1-year survival, and cause of death. RESULTS: Among 24 426 patients surviving >30 days, 1-year mortality was 8.5%. Older age groups had higher complication rates, and older age and complications were independently associated with 1-year mortality (P<0.0001). Increasing age was associated with a decrease in the proportion of deaths from colon cancer with a concomitant increase in the proportion of deaths from cardiovascular disease. Older age and sepsis were independently associated with higher risk of colon cancer-specific death (65-74: HR=1.59, 95% CI=1.26-2.00; ⩾75: HR=2.57, 95% CI=2.09-3.16; sepsis: HR=2.58, 95% CI=2.13-3.11) and cardiovascular disease-specific death (65-74: HR=3.72, 95% CI=2.29-6.05; ⩾75: HR=7.02, 95% CI=4.44-11.10; sepsis: HR=2.33, 95% CI=1.81-2.99). CONCLUSIONS: Older age and sepsis are associated with higher 1-year overall, cancer-specific, and cardiovascular-specific mortality, highlighting the importance of geriatric assessment, multidisciplinary care, and cardiovascular optimisation for older patients and those with infectious complications.

Variation in Delayed Time to Adjuvant Chemotherapy and Disease-Specific Survival in Stage III Colon Cancer Patients.

BACKGROUND: There is a paucity of literature quantifying the extent to which time to adjuvant chemotherapy for stage III colon cancer patients varies between individual surgeons, medical oncologists, and hospitals. METHODS: A retrospective cohort study was conducted by merging the New York State Cancer Registry with the Statewide Planning & Research Cooperative System and Medicare claims to identify stage III colon cancer patients from 2004 to 2009 who underwent resection and received adjuvant chemotherapy. Multilevel logistic regression models characterized variation in delayed time to adjuvant chemotherapy (>8 weeks vs. ≤8 weeks). Multilevel competing-risks Cox proportional hazards models assessed the effect of delayed time to adjuvant chemotherapy on disease-specific survival. RESULTS: The proportion of delayed time to adjuvant chemotherapy was 36 % in 1133 patients treated by 516 surgeons and 351 medical oncologists at 163 hospitals. After controlling for case-mix, the majority of the clustering variation (72 %) in delayed time to adjuvant chemotherapy is attributed to differences between medical oncologists. Risk-adjusted surgeon-specific, medical oncologist-specific, and hospital-specific probabilities of delayed time to adjuvant chemotherapy ranged from 30 to 38, 17 to 59, and 27 to 43 %, respectively. Delayed time to adjuvant chemotherapy was associated with disease-specific survival (hazard ratio [HR] 1.24, 95 % confidence interval [CI] 1.07-1.45). CONCLUSIONS: These findings suggest there is substantial variation in time to adjuvant chemotherapy among stage III colon cancer patients. Reasons for delays may be due to system factors that influence individual providers to make varying decisions on the time of initiation. Future research should identify what these factors may be and how to address them to promote better delivery of care.

Long-term Deleterious Impact of Surgeon Care Fragmentation After Colorectal Surgery on Survival: Continuity of Care Continues to Count.

BACKGROUND: Surgical care fragmentation at readmission impacts short-term outcomes. However, the long-term impact of surgical care fragmentation is unknown. OBJECTIVE: The purpose was to evaluate the impact of surgical care fragmentation, encompassing both surgeon and hospital care, at readmission after colorectal surgery on 1-year survival. DESIGN: This was a retrospective cohort study. SETTING: The study included patients undergoing colorectal resection in New York State from 2004 to 2014. PATIENTS: Included were 20,016 patients undergoing colorectal resection who were readmitted within 30 days of discharge and categorized by source-of-care fragmentation. Each readmission was classified by the source of fragmentation: readmission to the index hospital and managed by another provider, readmission to another hospital by the index surgeon, and readmission to another hospital by another provider. Patients readmitted to the index hospital and managed by the index surgeon served as controls. MAIN OUTCOME MEASURES: One-year overall survival and 1-year colorectal cancer-specific survival were the outcomes measured. RESULTS: After propensity adjustment, surgeon care fragmentation was independently associated with decreased survival. In comparison with patients without surgical care fragmentation (patients readmitted to the index hospital and managed by the index surgeon), patients readmitted to the index hospital and managed by another provider had over a 2-fold risk (HR, 2.33; 95% CI, 2.10-2.60) and patients readmitted to another hospital by another provider had almost a 2-fold risk (HR, 1.91; 95% CI, 1.63-2.25) of 1-year mortality. Among 9545 patients with a colorectal cancer diagnosis, surgical care fragmentation was once again associated with decreased survival with patients readmitted to the index hospital and managed by another provider having a HR of 2.12 (95% CI, 1.76-2.56) and patients readmitted to another hospital by another provider having a HR of 1.57 (95% CI, 1.17-2.11) compared with patients readmitted to the index hospital and managed by the index surgeon. LIMITATIONS: Limitations include possible miscoding of data, retrospective design, and selection bias. CONCLUSIONS: After accounting for patient, index hospital, index surgeon, and readmission factors, there is a significant 2-fold decrease in survival associated with surgeon care fragmentation regardless of hospital continuity. See Video Abstract at http://links.lww.com/DCR/A431.

Is the Distance Worth It? Patients With Rectal Cancer Traveling to High-Volume Centers Experience Improved Outcomes.

BACKGROUND: It is unclear whether traveling long distances to high-volume centers would compensate for travel burden among patients undergoing rectal cancer resection. OBJECTIVE: The purpose of this study was to determine whether operative volume outweighs the advantages of being treated locally by comparing the outcomes of patients with rectal cancer treated at local, low-volume centers versus far, high-volume centers. DESIGN: This was a population-based study. SETTINGS: The National Cancer Database was queried for patients with rectal cancer. PATIENTS: Patients with stage II or III rectal cancer who underwent surgical resection between 2006 and 2012 were included. MAIN OUTCOME MEASURES: The outcomes of interest were margins, lymph node yield, receipt of neoadjuvant chemoradiation, adjuvant chemotherapy, readmission within 30 days, 30-day and 90-day mortality, and 5-year overall survival. RESULTS: A total of 18,605 patients met inclusion criteria; 2067 patients were in the long-distance/high-volume group and 1362 in the short-distance/low-volume group. The median travel distance was 62.6 miles for the long-distance/high-volume group and 2.3 miles for the short-distance/low-volume group. Patients who were younger, white, privately insured, and stage III were more likely to have traveled to a high-volume center. When controlled for patient factors, stage, and hospital factors, patients in the short-distance/low-volume group had lower odds of a lymph node yield ≥12 (OR = 0.51) and neoadjuvant chemoradiation (OR = 0.67) and higher 30-day (OR = 3.38) and 90-day mortality (OR = 2.07) compared with those in the long-distance/high-volume group. The short-distance/low-volume group had a 34% high risk of overall mortality at 5 years compared with the long-distance/high-volume group. LIMITATIONS: We lacked data regarding patient and physician decision making and surgeon-specific factors. CONCLUSIONS: Our results indicate that when controlled for patient, tumor, and hospital factors, patients who traveled a long distance to a high-volume center had improved lymph node yield, neoadjuvant chemoradiation receipt, and 30- and 90-day mortality compared with those who traveled a short distance to a low-volume center. They also had improved 5-year survival. See Video Abstract at http://links.lww.com/DCR/A446.