Tiratricol, a thyroid hormone metabolite, has potent inhibitory activity against human dihydroorotate dehydrogenase.

Human dihydroorotate dehydrogenase (hDHODH) is a promising drug target for many diseases including autoimmune diseases, cancer, and viral infection. To develop more novel and potent hDHODH inhibitors, we screened our in-house library of old drugs. We found that tiratricol (3,3',5-triiodothyroacetic acid), a thyroid hormone metabolite, has potent hDHODH inhibitory activity (IC50 : 0.754 ± 0.126 µM), and its precursor tetrac (3,3',5,5'-tetraiodothyroacetic acid) also shows a certain inhibitory activity against hDHODH (IC50 : 11.960 ± 1.453 µM). Enzyme kinetic analysis shows that tiratricol and tetrac are noncompetitive inhibitors versus CoQ0 , which is different from the positive control A771726. ThermoFMN assay, molecular docking and site-directed mutagenesis all indicate that tiratricol and tetrac interact with more key residues of hDHODH than A771726, especially some hydrophobic residues in Subsite 1. In conclusion, our experiment results indicate a potential new use for the old drug, tiratricol, and provide a novel chemical scaffold for the design of hDHODH inhibitors.

Effect of Cr on Microstructure and Properties of WVTaTiCrx Refractory High-Entropy Alloy Laser Cladding.

WVTaTiCrx (x = 0, 0.25, 0.5, 0.75, 1) refractory high-entropy alloy coatings were prepared on a 42-CrMo steel plate using laser cladding. The purpose of this work is to investigate the effect of the Cr content on the microstructure and properties of the WVTaTiCrx coating. The morphologies and phase compositions of five coatings with different Cr contents were comparatively observed. In addition, the hardness and high-temperature oxidation resistance of the coatings were also analyzed. As a result, with the increase in Cr, the coating grains were more refined. All the coating is mainly composed of the BCC solid-solution phase, which promotes the precipitation of the Laves phase with the increase in Cr. The addition of Cr greatly improves the hardness, high-temperature oxidation resistance and corrosion resistance of the coating. The WVTaTiCr (Cr1) exhibited superior mechanical properties, especially in terms of its exceptional hardness, high-temperature oxidation resistance and outstanding corrosion resistance. The average hardness of the WVTaTiCr alloy coating reaches 627.36 HV. After 50 h of high-temperature oxidation, the oxide weight of WVTaTiCr increases by 5.12 mg/cm2, and the oxidation rate is 0.1 mg/(cm2·h). In 3.5 wt% NaCl solution, the corrosion potential of WVTaTiCr is -0.3198 V, and the corrosion rate is 0.161 mm/a.

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.

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 ).

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.

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.

What patient factors and Patient-Reported Outcomes Measurement Information System domains are associated with worse pain coping in pediatric orthopaedic patients in the United States?

We sought to better understand the relationship between Patient-Reported Outcomes Measurement Information System (PROMIS) mobility, pain interference (PI) and depressive symptoms scores, as well as determine what patient factors and PROMIS domains were associated with worse pain coping (PROMIS PI), in a pediatric orthopaedic population. Between 27 August 2015 and 30 April 2019, new pediatric orthopaedic patients 18 years or younger (or their guardians as a proxy) were asked to complete PROMIS mobility, PI and depressive symptoms domains at an academic medical center pediatric orthopaedic clinic. Pearson correlation coefficients (r) were calculated between each PROMIS domain. Linear multivariate regression analysis was used to determine patient characteristics and PROMIS domains associated with presenting PROMIS PI scores. There was a strong-moderate correlation between PROMIS mobility and PI (r = -0.66, P < 0.001), while the correlation between PROMIS mobility and depressive symptoms was moderate-poor (r = -0.38, P < 0.001). There was a moderate correlation between PROMIS depressive symptoms and PI (r = 0.54, P < 0.001). In multivariate linear regression analysis, female gender (ß = 0.82, P < 0.001), self-reported black race (ß = 0.94, P < 0.001), Medicaid insurance (ß = 0.82, P < 0.001) and worsening depressive symptoms (ß = 0.33, P < 0.001) were associated with worse pain coping mechanisms, while increasing mobility (ß = -0.47, P < 0.001) was associated with better pain coping mechanisms. Poor mobility and worse depressive symptoms are associated with worse pain coping mechanisms. Additionally, Medicaid insurance status, black race and female gender are also associated with worse physical limitations secondary to pain.

Quality Assurance, Metrics, and Improving Standards in Rectal Cancer Surgery in the United States.

Rectal cancer surgery has seen significant improvement in recent years. This has been possible in part due to focus on surgeon education and training, specific surgical quality metrics, and longitudinal tracking of data through the use of registries. In countries that have implemented such efforts, data has shown significant improvement in outcomes. However, there continues to be significant variation in rectal cancer outcomes and practices worldwide. Just within the United States, county level mortality rates from rectal cancer range from 8-15 per 100,000 to 38-59 per 100,000. In order to continue to improve rectal cancer patient outcomes, there needs to be evidence based guidelines and standards centered around the framework of structure, process, and outcomes. In addition, there must be a feedback system by which programs can continually assess their performance. Obtaining evidence for specific standards and measures can be challenging and requires analyzing available data and literature, some of which may be conflicting. This article evaluates the evolution of metrics and standards used for quality improvement in rectal cancer and ongoing efforts to further improve patient outcomes.

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.

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.

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.

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.

Hospital and surgeon variation in positive circumferential resection margin among rectal cancer patients.

BACKGROUND: The objective of this study was to evaluate variation in positive CRM at the surgeon and hospital levels and assess impact on disease-specific survival. METHODS: Patients with stage I-III rectal cancer were identified in New York State. Bayesian hierarchical regressions estimated observed-to-expected (O/E) ratios for each surgeon/hospital. Competing-risks analyses estimated disease-specific survival among patients who were treated by surgeons/hospitals with O/E > 1 compared to those with O/E ratio ≤ 1. RESULTS: Among 1,251 patients, 208 (17%) had a positive CRM. Of the 345 surgeons and 118 hospitals in the study, 99 (29%) and 48 (40%) treated a higher number of patients with CRM than expected, respectively. Patients treated by surgeons with O/E > 1 (HR = 1.38, 95% CI = 1.16, 1.67) and those treated at hospitals with O/E > 1 (HR = 1.44, 95% CI = 1.11, 1.85) had worse disease-specific survival. DISCUSSION: Surgeon and hospital performance in positive CRM is associated with worse prognosis suggesting opportunities to enhance referral patterns and standardize care.

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.

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.