A Randomized Crossover Trial Evaluating the Impact of Cultural Dexterity Training on Surgical Residents' Knowledge, Cross-Cultural Care, Skills, and Beliefs: The Provider Awareness and Cultural dexterity Training for Surgeons (PACTS) Trial.

OBJECTIVES: This trial examines the impact of the Provider Awareness and Cultural dexterity Toolkit for Surgeons (PACTS) curriculum on surgical residents' knowledge, cross-cultural care, skills, and beliefs. SUMMARY BACKGROUND DATA: Cross-cultural training of providers may reduce healthcare outcome disparities, but its effectiveness in surgical trainees is unknown. METHODS: PACTS focuses on developing skills needed for building trust, working with patients with limited English proficiency, optimizing informed consent, and managing pain. The PACTS trial was a randomized crossover trial of 8 academic general surgery programs in the United States: The Early group ("Early") received PACTS between Periods 1 and 2, while the Delayed group ("Delayed") received PACTS between Periods 2 and 3. Residents were assessed pre- and post-intervention on Knowledge, Cross-Cultural Care, Self-Assessed Skills, and Beliefs. Chi-square and Fisher's exact tests were conducted to evaluate within- and between-intervention group differences. RESULTS: Of 406 residents enrolled, 315 were exposed to the complete PACTS curriculum. Early residents' Cross-Cultural Care (79.6% to 88.2%, P<0.0001), Self-Assessed Skills (74.5% to 85.0%, P<0.0001), and Beliefs (89.6% to 92.4%, P=0.0028) improved after PACTS; Knowledge scores (71.3% to 74.3%, P=0.0661) were unchanged. Delayed resident scores pre- to post-PACTS showed minimal improvements in all domains. When comparing the two groups at Period 2, Early residents had modest improvement in all 4 assessment areas, with statistically significant increase in Beliefs (92.4% vs 89.9%, P=0.0199). CONCLUSION: The PACTS curriculum is a comprehensive tool that improved surgical residents' knowledge, preparedness, skills, and beliefs, which will help with caring for diverse patient populations.

Lateral Pelvic Nodal Management and Patterns of Failure in Patients Receiving Short-Course Radiation for Locally Advanced Rectal Cancer.

BACKGROUND: Management of lateral pelvic lymph nodes in locally advanced rectal cancer is controversial, with limited data indicating the optimal approach. In addition, no data exist regarding the treatment of lateral nodes in the setting of short-course radiation and nonoperative intent. OBJECTIVE: To evaluate a novel approach incorporating simultaneous integrated boost to suspicious lateral nodes. DESIGN: A retrospective study. SETTING: This study was conducted at a large tertiary referral center. PATIENTS: Patients treated with radiation therapy and consolidation chemotherapy were included. All primary tumors underwent biopsy confirmation and disease staging with pelvic MRI. INTERVENTIONS: Primary tumors were biopsy proven and staged with pelvic MRI. A subset of lateral pelvic lymph node patients received a simultaneous integrated boost of 35 Gy in 5 fractions. Then, chemotherapy was administered, with the majority receiving modified folinic acid, fluorouracil, and oxaliplatin. Clinical partial response required total mesorectal excision. MAIN OUTCOME MEASURES: Patterns of failure and survival analyses by subgroup were assessed. Outcomes based on receipt of radiation were compared across node status. RESULTS: Between January 2017 and January 2022, 155 patients were treated with short-course chemotherapy, with 121 included in the final analysis. Forty-nine percent of patients underwent nonoperative management. The median follow-up was 36 months and the median age was 58 years. Thirty-eight patients (26%) had positive lateral pelvic lymph nodes. Comparing lateral node status, progression-free survival was significantly worse for patients with positive disease ( p < 0.001), with a trend for worse overall survival. Receipt of nodal boost in patients with lateral nodes resulted in meaningful locoregional control. Nodal boost did not contribute to additional acute or late GI toxicity. LIMITATIONS: Limitations include retrospective nature and lack of lateral node pathology; however, a thorough radiographic review was performed. CONCLUSIONS: Lateral node-positive rectal cancer is correlated with worse oncologic outcomes and higher locoregional failure. Boost to clinically positive lateral nodes is a safe approach in the setting of short course radiation and in those receiving nonoperative intent. See Video Abstract. MANEJO DE LOS GANGLIOS PLVICOS LATERALES Y PATRONES DE FALLA EN PACIENTES QUE RECIBEN RADIACIN DE CICLO CORTO PARA EL CNCER DE RECTO LOCALMENTE AVANZADO: ANTECEDENTES:El manejo de los ganglios linfáticos pélvicos laterales en el cáncer de recto localmente avanzado es controvertido, con datos limitados que indiquen el abordaje óptimo. Además, no existen datos sobre el tratamiento de los ganglios linfáticos laterales en el contexto de la radiación de curso corto y la intención no operatoria.OBJETIVO:Evaluamos un enfoque novedoso que incorpora sobreimpresión integrada simultánea (SIB) a los linfonodos laterales sospechosos.DISEÑO:Este fue un estudio retrospectivo.ESCENARIO:Este estudio se realizó en un gran centro de referencia terciario.PACIENTES:Se incluyeron pacientes tratados con radiación y quimioterapia de consolidación. Todos los tumores primarios se confirmaron mediante biopsia y la enfermedad se estadificó con resonancia magnética pélvica.INTERVENCIONES:Los tumores primarios se confirmaron mediante biopsia y se estadificaron con RM pélvica. Un subconjunto de pacientes con linfonodos pélvicos laterales (LPLN) recibió SIB a 35 Gy en 5 fracciones. Luego, se administró quimioterapia y la mayoría recibió mFOLFOX. La respuesta clínica parcial requirió la escisión total del mesorrecto.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron los patrones de fracaso y los análisis de supervivencia por subgrupo. Los resultados basados en el esquema de radiación se compararon según el estado de los ganglios.RESULTADOS:Entre enero de 2017 y enero de 2022, 155 pacientes fueron tratados con ciclo corto y quimioterapia con 121 incluidos en el análisis final. El 49% se sometió a manejo no operatorio. La mediana de seguimiento fue de 36 meses y la mediana de edad fue de 58 años. 38 pacientes (26%) tuvieron LPLN positivos. Comparando el estado de los ganglios laterales, la supervivencia libre de progresión fue significativamente peor para los pacientes con LPLN positiva ( p < 0,001) con una tendencia a una peor supervivencia global. La recepción de refuerzo nodal en pacientes con nodos laterales dio como resultado un control locorregional significativo. La sobreimpresión ganglionar no contribuyó a la toxicidad GI aguda o tardía adicional.LIMITACIONES:Las limitaciones incluyeron la naturaleza retrospectiva y la falta de patología de los ganglios linfáticos laterales; sin embargo, se realizó una revisión radiográfica exhaustiva.CONCLUSIONES:El cáncer de recto con ganglio lateral positivo se correlaciona con peores resultados oncológicos y mayor fracaso locorregional. La sobreimpresión a los ganglios laterales clínicamente positivos es un enfoque seguro en el contexto de un curso corto y en aquellos que siguen un manejo no operatorio. (Traducción-Dr. Felipe Bellolio ).

Association of Surgical Approaches and Outcomes in Total Mesorectal Excision and Margin Status for Rectal Cancer.

INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer. METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected from the US Rectal Cancer Consortium database (2007-2017). Quasi-Poisson regression analysis with backward selection was used to investigate the relationship between the surgical approach and outcomes of interest. RESULTS: Among the 664 patients included in the study, the distribution of surgical approaches was as follows: 351 (52.9%) underwent TME via the open approach, 159 (23.9%) via the robotic approach, and 154 (23.2%) via the laparoscopic approach. There were no significant differences in baseline demographics among the three cohorts. The laparoscopic cohort had fewer patients with low rectal cancer (<6 cm from the anal verge) than the robotic and open cohorts (Lap 28.6% versus Rob 59.1% versus Open 45.6%, P = 0.015). Patients who underwent Rob and Lap TME had lower intraoperative blood loss compared with the Open approach (Rob 200 mL [Q1, Q3: 100.0, 300.0] versus Lap 150 mL [Q1, Q3: 75.0, 250.0] versus Open 300 mL [Q1, Q3: 150.0, 600.0], P < 0.001). There was no difference in the operative time (Rob 243 min [Q1, Q3: 203.8, 300.2] versus Lap 241 min [Q1, Q3: 186, 336] versus Open 226 min [Q1, Q3: 178, 315.8], P = 0.309) between the three approaches. Postoperative length of stay was shorter with robotic and laparoscopic approach compared to open approach (Rob 5.0 d [Q1, Q3: 4, 8.2] versus Lap 5 d [Q1, Q3: 4, 8] versus Open 7.0 d [Q1, Q3: 5, 9], P < 0.001). There was no statistically significant difference in the quality of TME between the robotic, laparoscopic, and open approaches (79.2%, 64.9%, and 64.7%, respectively; P = 0.46). The margin positivity rate, a composite of circumferential margin and distal margin, was higher with the robotic and open approaches than with the laparoscopic approach (Rob 8.2% versus Open 6.6% versus Lap 1.9%, P = 0.17), Rob versus Lap (odds ratio 0.21; 95% confidence interval 0.05, 0.83) and Rob versus Open (odds ratio 0.5; 95% confidence interval 0.22, 1.12). There was no difference in long-term survival, including overall survival and recurrence-free survival, between patients who underwent robotic, laparoscopic, or open TME (Figure 1). CONCLUSIONS: In patients undergoing surgery with curative intent for rectal cancer, we did not observe a difference in the quality of TME between the robotic, laparoscopic, or open approaches. Robotic and open TME compared to laparoscopic TME were associated with higher margin positivity rates in our study. This was likely due to the higher percentage of low rectal cancers in the robotic and open cohorts. We also reported no significant differences in overall survival and recurrence-free survival between the aforementioned surgical techniques.

Prophylactic defunctioning stomas improve clinical outcomes of anastomotic leak following rectal cancer resections: An analysis of the US Rectal Cancer Consortium.

PURPOSE: Anastomotic leak (AL) is a complication of low anterior resection (LAR) that results in substantial morbidity. There is immense interest in evaluating immediate postoperative and long-term oncologic outcomes in patients who undergo diverting loop ileostomies (DLI). The purpose of this study is to understand the relationship between fecal diversion, AL, and oncologic outcomes. METHODS: This is a retrospective multicenter cohort study using patient data obtained from the US Rectal Cancer Consortium database compiled from six academic institutions. The study population included patients with rectal adenocarcinoma undergoing LAR. The primary outcome was the incidence of AL among patients who did or did not receive DLI during LAR. Secondary outcomes included risk factors for AL, receipt of adjuvant therapy, 3-year overall survival, and 3-year recurrence. RESULTS: Of 815 patients, 38 (4.7%) suffered AL after LAR. Patients with AL were more likely to be male, have unintentional preoperative weight loss, and are less likely to undergo DLI. On multivariable analysis, DLI remained protective against AL (p < 0.001). Diverted patients were less likely to undergo future surgical procedures including additional ostomy creation, completion proctectomy, or pelvic washout for AL. Subgroup analysis of 456 patients with locally advanced disease showed that DLI was correlated with increased receipt of adjuvant therapy for patients with and without AL on univariate analysis (SHR:1.59; [95% CI 1.19-2.14]; p = 0.002), but significance was not met in multivariate models. CONCLUSION: Lack of DLI and preoperative weight loss was associated with anastomotic leak. Fecal diversion may improve the timely initiation of adjuvant oncologic therapy. The long-term outcomes following routine diverting stomas warrant further study.

Surgical Decision-Making in Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder affecting patients with germline mutations of the adenomatous polyposis coli (APC) tumor suppressor gene. The surgical treatment of colorectal disease in FAP, which has the goal of colorectal cancer prevention, varies based on both patient and disease factors but can include the following: total colectomy with ileorectal anastomosis, proctocolectomy with stapled or hand-sewn ileal pouch-anal anastomosis, or total proctocolectomy with end ileostomy. The operative options and extent of resection, as well as the use of endoscopy and chemoprevention for the management of polyposis, will be discussed in detail in this article. In addition, commonly debated management decisions related to the treatment of patients with FAP, including the timing of prophylactic colorectal resections for patients with FAP and management of the polyp burden in the rectum, will be discussed. Finally, genotype considerations and the impact of desmoid disease on operative decisions in the setting of FAP will also be reviewed.

Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis.

BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown. METHODS: We evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time). The patients were then randomly assigned in a 1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once daily for up to 48 months. The primary end point, assessed in a time-to-event analysis, was disease progression, defined as a composite of major surgery, endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in the rectum or pouch, or progression of duodenal disease. RESULTS: A total of 171 patients underwent randomization. Disease progression occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine-sulindac as compared with sulindac (P = 0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine. Among 37 precolectomy patients, the corresponding values in the treatment groups were 2 of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 (18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 [95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse and serious adverse events were similar across the treatment groups. CONCLUSIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, NCT01483144; EudraCT number, 2012-000427-41.).

Discharge Prescribing Protocol Decreases Opioids in Circulation and Does Not Increase Refills After Colorectal Surgery.

BACKGROUND: Up to 10% of patients develop new, persistent opioid use after surgery. We aimed to assess our prescribing practices and patient utilization of opioids after colorectal surgery. OBJECTIVE: This study aimed to implement an opioid-prescribing protocol that will minimize the number of postoperative opioids to decrease community circulation and persistent use by patients. DESIGN: This was a single-institution, prospective study based on questionnaires of postoperative patients in 2019 and 2020 to determine opioid prescribing and usage patterns. Based on these preliminary results, a protocol was implemented in which patients were discharged with 5 or 15 oxycodone 5 mg equivalents based on opioid usage in the 24 hours before discharge. Patients were surveyed after protocol implementation. SETTINGS: Our institution is a large referral center for surgical treatment of colorectal disease. PATIENTS: Adults who underwent inpatient abdominal colorectal procedures. MAIN OUTCOME MEASURES: End points included the number of opioids prescribed, number of prescribed opioids taken, and refill rate. Nonparametric testing was used. RESULTS: Of 77 eligible patients, 61 were opioid naive. Preprotocol, opioid-naive patients (n = 29) were prescribed a median of 30 (interquartile range [IQR], 30-45) tablets but took only 10 (IQR, 0-10; p < 0.0001). Eighty-three percent took 20 or fewer tablets. After protocol implementation, opioid-naive patients (n = 32) were prescribed fewer tablets (median 15; IQR, 7-15; p < 0.0001) but took a similar number of tablets as the preprotocol group (median 10; IQR, 0-10; p = 0.21). The refill rate remained similar (13.8% vs 18.8%; p = 0.60). Protocol adherence was 90.6%. LIMITATIONS: This study is limited by sample size, cohort heterogeneity, and generalizability. CONCLUSIONS: Patients took significantly fewer opioids than were prescribed. Our protocol limited overprescribing and resulted in fewer opioids in the community without opportunity costs such as increased refills. Long-term studies are needed to assess the effects of persistent opioid use after surgery. See Video Abstract at http://links.lww.com/DCR/C93 .

ANTECEDENTES: Hasta el 10% de los pacientes desarrollan un nuevo uso persistente de opioides después de la cirugía. Nuestro objetivo fue evaluar nuestras prácticas de prescripción y la utilización de opioides por parte de los pacientes después de la cirugía colorrectal. OBJETIVO: Nuestro objetivo es implementar un protocolo de prescripción de opioides que minimice la cantidad de opioides posoperatorios para disminuir la circulación en la comunidad y el uso persistente por parte de los pacientes. DISEÑO: Estudio prospectivo, de una sola institución, basado en cuestionarios de pacientes postoperatorios en 2019 y 2020 para determinar los patrones de prescripción y uso de opioides. Con base en estos resultados preliminares, se implementó un protocolo en el que los pacientes eran dados de alta con 5 o 15 equivalentes de oxicodona de 5 mg según el uso de opioides en las 24 horas previas al alta. Los pacientes fueron encuestados después de la implementación del protocolo. AJUSTES: Nuestra institución es un gran centro de referencia para el tratamiento quirúrgico de la enfermedad colorrectal. PACIENTES: Adultos que se sometieron a procedimientos colorrectales abdominales con hospitalización. PRINCIPALES MEDIDAS DE RESULTADO: Los criterios de valoración incluyeron el número de opioides recetados, el número de opioides recetados tomados y la tasa de reabastecimiento. Se utilizaron pruebas no paramétricas. RESULTADOS: De 77 pacientes elegibles, 61 no habian recibido opioides. A los pacientes sin tratamiento previo con opioides antes del protocolo (n = 29) se les prescribió una mediana de 30 (rango intercuartilico [RIC] 30­45) comprimidos, pero solo tomaron 10 (RIC 0.10, p < 0,0001). El ochenta y tres por ciento tomo ≤20 comprimidos. Despues de la implementacion del protocolo, a los pacientes sin tratamiento previo con opioides (n = 32) se les prescribieron menos comprimidos (15; RIC 7.15, p < 0,0001), pero tomaron un numero similar antes de la intervención (10; RIC 0­10, p = 0,21). La tasa de reabastecimiento se mantuvo similar (13,8% frente a 18,8%, p = 0,60). La adherencia al protocolo fue del 90,6%. LIMITACIONES: Este estudio está limitado por el tamaño de la muestra, la heterogeneidad de la cohorte y la generalización. CONCLUSIONES: Los pacientes tomaron significativamente menos opioides de los prescritos. Nuestro protocolo limitó la prescripción excesiva y dio como resultados menos opioides en la comunidad sin costos de oportunidad, como el aumento de reabastecimiento. Se necesitan estudios a largo plazo para evaluar los efectos sobre el uso persistente de opioides después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/C93 . (Traducción­Dr. Francisco M. Abarca-Rendon).

Circumferential Resection Margin as Predictor of Nonclinical Complete Response in Nonoperative Management of Rectal Cancer.

BACKGROUND: Short-course radiation therapy and consolidation chemotherapy with nonoperative intent has emerged as a novel treatment paradigm for patients with rectal cancer, but there are no data on the predictors of clinical complete response. OBJECTIVE: Evaluate the predictors of clinical complete response and survival. DESIGN: Retrospective cohort. SETTINGS: National Cancer Institute-designated cancer center. PATIENTS: Patients with stage I to III rectal adenocarcinoma treated between January 2018 and May 2019 (n = 86). INTERVENTIONS: Short-course radiation therapy followed by consolidation chemotherapy. MAIN OUTCOME MEASURES: Logistic regression was performed to assess for predictors of clinical complete response. The end points included local regrowth-free survival, regional control, distant metastasis-free survival, and overall survival. RESULTS: A positive (+) circumferential resection margin by MRI at diagnosis was a significant predictor of nonclinical complete response (OR: 4.1, p = 0.009) when adjusting for CEA level and primary tumor size. Compared to patients with a negative (-) pathologic circumferential resection margin, patients with a positive (+) pathologic circumferential resection margin had inferior local regrowth-free survival (29% vs 87%, p < 0.001), regional control (57% vs 94%, p < 0.001), distant metastasis-free survival (43% vs 95%, p < 0.001), and overall survival (86% vs 95%, p < 0.001) at 2 years. However, the (+) and (-) circumferential resection margin by MRI subgroups in patients who had a clinical complete response both had similar regional control, distant metastasis-free survival, and overall survival of more than 90% at 2 years. LIMITATIONS: Retrospective design, modest sample size, short follow-up, and the heterogeneity of treatments. CONCLUSIONS: Circumferential resection margin involvement by MRI at diagnosis is a strong predictor of nonclinical complete response. However, patients who achieve a clinical complete response after short-course radiation therapy and consolidation chemotherapy with nonoperative intent have excellent clinical outcomes regardless of the initial circumferential resection margin status. See Video Abstract at http://links.lww.com/DCR/C190 . EL MARGEN DE RESECCIN CIRCUNFERENCIAL COMO PREDICTOR NO CLNICO DE RESPUESTA COMPLETA EN EL MANEJO CONSERVADOR DEL CNCER DE RECTO: ANTECEDENTES:La radioterapia de corta duración y la quimioterapia de consolidación en el manejo conservador, han surgido como un nuevo paradigma de tratamiento, para los pacientes con cáncer de recto, lastimosamente no hay datos definitivos sobre los predictores de una respuesta clínica completa.OBJETIVO:Evaluar los predictores de respuesta clínica completa y de la sobrevida.DISEÑO:Estudio retrospectivo de cohortes.AJUSTES:Centro oncológico designado por el NCI.PACIENTES:Adenocarcinomas de recto estadio I-III tratados entre 01/2018 y 05/2019 (n = 86).INTERVENCIONES:Radioterapia de corta duración seguida de quimioterapia de consolidación.PRINCIPALES MEDIDAS DE RESULTADO:Se realizó una regresión logística para evaluar los predictores de respuesta clínica completa. Los criterios de valoración incluyeron la sobrevida libre de recidiva local, el control regional, la sobrevida libre de metástasis a distancia y la sobrevida general.RESULTADOS:Un margen de resección circunferencial positivo (+) evaluado por imagenes de resonancia magnética nuclear en el momento del diagnóstico fue un predictor no clínico muy significativo de respuesta completa (razón de probabilidades/ OR: 4,1, p = 0,009) al ajustar el nivel de antígeno carcinoembrionario y el tamaño del tumor primario. Comparando con los pacientes que presetaban un margen de resección circunferencial patológico negativo (-), los pacientes con un margen de resección circunferencial patológico positivo (+) tuvieron una sobrevida libre de recidiva local (29% frente a 87%, p < 0,001), un control regional (57% frente a 94%, p < 0,001), una sobrevida libre de metástasis a distancia (43% frente a 95%, p < 0,001) y una sobrevida global (86% frente a 95%, p < 0,001) inferior en 2 años de seguimiento. Sin embargo, los subgrupos de margen de resección circunferencial (+) y (-) evaluados por imágenes de resonancia magnética nuclear en pacientes que tuvieron una respuesta clínica completa tuvieron un control regional similar, una sobrevida libre de metástasis a distancia y una sobrevida general >90% en 2 años de seguimiento.LIMITACIONES:Diseño retrospectivo, tamaño modesto de la muestra, seguimiento corto y heterogeneidad de tratamientos.CONCLUSIONES:La afectación del margen de resección circunferencial evaluado por resonancia magnética nuclear al momento del diagnóstico es un fuerte factor predictivo no clínico de respuesta completa. Sin embargo, los pacientes que logran una respuesta clínica completa después de un curso corto de radioterapia y quimioterapia de consolidación como manejo conservador tienen excelentes resultados clínicos independientemente del estado del margen de resección circunferencial inicial. Consulte Video Resumen en http://links.lww.com/DCR/C190 . (Traducción-Dr. Xavier Delgadillo ).

Perioperative Complications After Proctectomy for Rectal Cancer: Does Neoadjuvant Regimen Matter?

OBJECTIVE: Investigate the association between neoadjuvant treatment strategy and perioperative complications in patients undergoing proctectomy for nonmetastatic rectal cancer. SUMMARY OF BACKGROUND DATA: Neoadjuvant SC-TNT is an alternative to neoadjuvant CRT for rectal cancer. Some have argued that short-course radiation and extended radiation-to-surgery intervals increase operative difficulty and complication risk. However, the association between SC-TNT and surgical complications has not been previously investigated. METHODS: This single-center retrospective cohort study included patients undergoing total mesorectal excision for nonmetastatic rectal cancer after SC-TNT or CRT between 2010 and 2018. Univariate analysis of severe POM and multiple secondary outcomes, including overall POM, intraoperative complications, and resection margins, was performed. Logistic regression of severe POM was also performed. RESULTS: Of 415 included patients, 156 (38%) received SC-TNT and 259 (62%) received CRT. The cohorts were largely similar, though patients with higher tumors (69.9% vs 47.5%, P < 0.0001) or node-positive disease (76.9% vs 62.6%, P = 0.004) were more likely to receive SC-TNT. We found no difference in incidence of severe POM (9.6% SC-TNT vs 12.0% CRT, P = 0.46) or overall POM (39.7% SC-TNT vs 37.5% CRT, P = 0.64) between cohorts. Neoadjuvant regimen was also not associated with a difference in severe POM (odds ratio 0.42, 95% confidence interval 0.04-4.70, P = 0.48) in multivariate analysis. There was no significant association between neoadjuvant regimen and any secondary outcome. CONCLUSION: In rectal cancer patients treated with SC-TNT and proctectomy, we found no significant association with POM compared to patients undergoing CRT. SC-TNT does not significantly increase the risk of POM compared to CRT.

The effects of armed conflict on the health of women and children.

Women and children bear substantial morbidity and mortality as a result of armed conflicts. This Series paper focuses on the direct (due to violence) and indirect health effects of armed conflict on women and children (including adolescents) worldwide. We estimate that nearly 36 million children and 16 million women were displaced in 2017, on the basis of international databases of refugees and internally displaced populations. From geospatial analyses we estimate that the number of non-displaced women and children living dangerously close to armed conflict (within 50 km) increased from 185 million women and 250 million children in 2000, to 265 million women and 368 million children in 2017. Women's and children's mortality risk from non-violent causes increases substantially in response to nearby conflict, with more intense and more chronic conflicts leading to greater mortality increases. More than 10 million deaths in children younger than 5 years can be attributed to conflict between 1995 and 2015 globally. Women of reproductive ages living near high intensity conflicts have three times higher mortality than do women in peaceful settings. Current research provides fragmentary evidence about how armed conflict indirectly affects the survival chances of women and children through malnutrition, physical injuries, infectious diseases, poor mental health, and poor sexual and reproductive health, but major systematic evidence is sparse, hampering the design and implementation of essential interventions for mitigating the harms of armed conflicts.

The political and security dimensions of the humanitarian health response to violent conflict.

The nature of armed conflict throughout the world is intensely dynamic. Consequently, the protection of non-combatants and the provision of humanitarian services must continually adapt to this changing conflict environment. Complex political affiliations, the systematic use of explosive weapons and sexual violence, and the use of new communication technology, including social media, have created new challenges for humanitarian actors in negotiating access to affected populations and security for their own personnel. The nature of combatants has also evolved as armed, non-state actors might have varying motivations, use different forms of violence, and engage in a variety of criminal activities to generate requisite funds. New health threats, such as the COVID-19 pandemic, and new capabilities, such as modern trauma care, have also created new challenges and opportunities for humanitarian health provision. In response, humanitarian policies and practices must develop negotiation and safety capabilities, informed by political and security realities on the ground, and guidance from affected communities. More fundamentally, humanitarian policies will need to confront a changing geopolitical environment, in which traditional humanitarian norms and protections might encounter wavering support in the years to come.

Delivering health interventions to women, children, and adolescents in conflict settings: what have we learned from ten country case studies?

Armed conflict disproportionately affects the morbidity, mortality, and wellbeing of women, newborns, children, and adolescents. Our study presents insights from a collection of ten country case studies aiming to assess the provision of sexual, reproductive, maternal, newborn, child, and adolescent health and nutrition interventions in ten conflict-affected settings in Afghanistan, Colombia, Democratic Republic of the Congo, Mali, Nigeria, Pakistan, Somalia, South Sudan, Syria, and Yemen. We found that despite large variations in contexts and decision making processes, antenatal care, basic emergency obstetric and newborn care, comprehensive emergency obstetric and newborn care, immunisation, treatment of common childhood illnesses, infant and young child feeding, and malnutrition treatment and screening were prioritised in these ten conflict settings. Many lifesaving women's and children's health (WCH) services, including the majority of reproductive, newborn, and adolescent health services, are not reported as being delivered in the ten conflict settings, and interventions to address stillbirths are absent. International donors remain the primary drivers of influencing the what, where, and how of implementing WCH interventions. Interpretation of WCH outcomes in conflict settings are particularly context-dependent given the myriad of complex factors that constitute conflict and their interactions. Moreover, the comprehensiveness and quality of data remain limited in conflict settings. The dynamic nature of modern conflict and the expanding role of non-state armed groups in large geographic areas pose new challenges to delivering WCH services. However, the humanitarian system is creative and pluralistic and has developed some novel solutions to bring lifesaving WCH services closer to populations using new modes of delivery. These solutions, when rigorously evaluated, can represent concrete response to current implementation challenges to modern armed conflicts.

Combination of Sulindac and Eflornithine Delays the Need for Lower Gastrointestinal Surgery in Patients With Familial Adenomatous Polyposis: Post Hoc Analysis of a Randomized Clinical Trial.

BACKGROUND: Colectomy and proctocolectomy are the initial standard of care for patients with familial adenomatous polyposis. Pharmacotherapy to prevent the progression of polyposis and surgeries in the lower GI tract would be beneficial to patients with this disease. OBJECTIVE: This analysis aimed to evaluate the impact of eflornithine-sulindac combination versus monotherapy in delaying time to disease progression in the lower GI tract of patients with familial adenomatous polyposis. DESIGN: This is a post hoc analysis of a randomized phase 3 trial. SETTING: This study was conducted in 21 hospitals in 7 countries treating patients with familial adenomatous polyposis. PATIENTS: Adults with familial adenomatous polyposis were randomly assigned 1:1:1 into 3 arms. INTERVENTIONS: Patients received either eflornithine (750 mg), sulindac (150 mg), or both once daily for up to 48 months. MAIN OUTCOME MEASURES: Efficacy was evaluated as the time from randomization to predefined primary disease progression end points. RESULTS: A total of 158 patients were included in the study. Disease progression was observed in 2 of 54 (3.7%), 9 of 53 (17.0%), and 10 of 51 (19.6%) patients with at least partial lower GI tract in the combination, sulindac, and eflornithine arms, corresponding to risk reductions of 80% (p = 0.02) and 83% (p = 0.01) between combination and sulindac or eflornithine. When endoscopic excision of adenomas ≥10 mm in size was censored, the need for major surgery was observed in 0 of 54, 7 of 53 (13.2%), and 8 of 51 (15.7%) patients in the combination, sulindac, and eflornithine arms, corresponding to risk reductions approaching 100% between combination and sulindac (p = 0.005) or combination and eflornithine (p = 0.003). LIMITATIONS: This was a post hoc analysis, the sample size was small, and there were fewer than expected events. CONCLUSIONS: Eflornithine-sulindac combination therapy was superior to either drug alone in delaying or preventing the need for lower GI tract surgery in patients with familial adenomatous polyposis. See Video Abstract at http://links.lww.com/DCR/B658. REGISTRATION: ClinicalTrials.gov, NCT01483144; EU Clinical Trials Register, EudraCT 2012-000427-41. LA COMBINACIN DE SULINDAC Y EFLORNITINA RETRASA LA NECESIDAD DE CIRUGA DEL TUBO DIGESTIVO BAJO EN PACIENTES CON PAF ANLISIS POSTHOC DE UN ENSAYO CLNICO ALEATORIZADO: ANTECEDENTES:La colectomía y la proctocolectomía son el estándar inicial de atención para los pacientes con poliposis adenomatosa familiar. La farmacoterapia para prevenir la progresión de la poliposis y las cirugías en el tracto gastrointestinal inferior sería beneficiosa para los pacientes con esta enfermedad.OBJETIVO:Este análisis tuvo como objetivo evaluar el impacto de la combinación de eflornitina-sulindac versus la monoterapia en el retraso del tiempo hasta la progresión de la enfermedad en el tracto gastrointestinal inferior de pacientes con poliposis adenomatosa familiar.DISEÑO:Este es un análisis posthoc de un ensayo de fase 3 aleatorizado.ENTORNO CLINICO:Veintiún hospitales en 7 países que tratan a pacientes con poliposis adenomatosa familiar.PACIENTES:Adultos con poliposis adenomatosa familiar fueron aleatorizados 1: 1: 1 en 3 brazos.INTERVENCIONES:Los pacientes recibieron eflornitina (750 mg), sulindac (150 mg) o ambos una vez al día durante un máximo de 48 meses.PRINCIPALES MEDIDAS DE VALORACION:La eficacia se evaluó como el tiempo desde la aleatorización hasta los criterios de valoración primarios predefinidos de progresión de la enfermedad.RESULTADOS:Los resultados se informan para la población de estudio excluyendo a los pacientes que se habían sometido a ileostomías permanentes (n = 158). Se observó progresión de la enfermedad en 2/54 (3,7%), 9/53 (17,0%) y 10/51 (19,6%) pacientes con al menos tracto gastrointestinal inferior parcial en los brazos de combinación, sulindac y eflornitina, respectivamente, correspondientes al riesgo de reducciones del 80% (p = 0,02) y del 83% (p = 0,01) entre la combinación y el sulindaco o la eflornitina, respectivamente. Cuando se censuró la escisión endoscópica de adenomas ≥10 mm de tamaño, se observó la necesidad de cirugía mayor en 0/54, 7/53 (13,2%) y 8/51 (15,7%) pacientes en la combinación, sulindac y eflornitina, respectivamente, correspondientes a reducciones de riesgo cercanas al 100% entre combinación y sulindac (p = 0,005) o combinación y eflornitina (p = 0,003).LIMITACIONES:Este fue un análisis posthoc, el tamaño de la muestra fue pequeño y hubo menos eventos de los esperados.CONCLUSIONES:La terapia de combinación de eflornitina-sulindac fue superior a cualquier fármaco solo para retrasar o prevenir la necesidad de cirugía del tracto gastrointestinal inferior en pacientes con poliposis adenomatosa familiar. Consulte Video Resumen en http://links.lww.com/DCR/B658.

Travel Time to a High Volume Center Negatively Impacts Timing of Care in Rectal Cancer.

BACKGROUND: Regionalization of rectal cancer surgery may lead to worse disease free survival owing to longer travel time to reach a high volume center yet no study has evaluated this relationship at a single high volume center volume center. MATERIALS AND METHODS: This was a retrospective review of rectal cancer patients undergoing surgery from 2009 to 2019 at a single high volume center. Patients were divided into two groups based on travel time. The primary outcome was disease-free survival (DFS). Additional outcomes included treatment within 60 d of diagnosis, completeness of preoperative staging, and evaluation by a colorectal surgeon prior to initiation of treatment. RESULTS: A lower proportion of patients with long travel time began definitive treatment within 60 d of diagnosis (74.0% versus 84.0%, P= 0.01) or were seen by the treating colorectal surgeon before beginning definitive treatment (74.8% versus 85.4%, P < 0.01). On multivariable logistic regression analysis, patients with long travel time were significantly less likely to begin definitive treatment within 60 d of diagnosis (OR = 0.54; 95% CI = 0.31-0.93) or to be evaluated by a colorectal surgeon prior to initiating treatment (OR = 0.45; 95% CI = 0.25-0.80). There were no significant differences in DFS based on travel time. CONCLUSIONS: Although patients with long travel times may be vulnerable to delayed, lower quality rectal cancer care, there is no difference in DFS when definitive surgery is performed at a high volume canter. Ongoing research is needed to identify explanations for delays in treatment to ensure all patients receive the highest quality care.

Policy in pediatric nephrology: successes, failures, and the impact on disparities.

Pediatric nephrology has a history rooted in pediatric advocacy and has made numerous contributions to child health policy affecting pediatric kidney diseases. Despite this progress, profound social disparities remain for marginalized and socially vulnerable children with kidney disease. Different risk factors, such as genetic predisposition, environmental factors, social risk factors, or health care access influence the emergence and progression of pediatric kidney disease, as well as access to life-saving interventions, leading to disparate outcomes. This review will summarize the breadth of literature on social determinants of health in children with kidney disease worldwide and highlight policy-based initiatives that mitigate the adverse social factors to generate greater equity in pediatric kidney disease.

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

Motivation: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia. Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified. Availability and implementation: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/. Supplementary information: Supplementary data are available at Bioinformatics online.

Studies of human twins reveal genetic variation that affects dietary fat perception.

To learn more about the mechanisms of human dietary fat perception, 398 human twins rated fattiness and liking for six types of potato chips that differed in triglyceride content (2.5, 5, 10, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness and liking for the potato chips were reliable (r = 0.31-0.62, p < 0.05) and heritable (up to h2 = 0.29, p < 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, p < 1×10-5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was (a) negatively affected by the addition of a saturated fatty acid and (b) related to inborn genetic variants. These data suggest liking for dietary fat is not due solely to fatty acid content and highlight new candidate genes and proteins within this sensory pathway.

Advancing human health in the decade ahead: pregnancy as a key window for discovery: A Burroughs Wellcome Fund Pregnancy Think Tank.

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future effects that hold great potential in 3 major areas: developmental genomics, including the application of methodologies designed to bridge genotypes, physiology, and diseases, addressing vexing questions in early human development; gestational physiology, from immune tolerance to growth and the timing of parturition; and personalized and population medicine, focusing on amalgamating health record data and deep phenotypes to create broad knowledge that can be integrated into healthcare systems and drive discovery to address pregnancy-related disease and promote general health. We propose a series of questions reflecting development, systems biology, diseases, clinical approaches and tools, and population health, and a call for scientific action. Clearly, transdisciplinary science must advance and accelerate to address adverse pregnancy outcomes. Disciplines not traditionally involved in the reproductive sciences, such as computer science, engineering, mathematics, and pharmacology, should be engaged at the study design phase to optimize the information gathered and to identify and further evaluate potentially actionable therapeutic targets. Information sources should include noninvasive personalized sensors and monitors, alongside instructive "liquid biopsies" for noninvasive pregnancy assessment. Future research should also address the diversity of human cohorts in terms of geography, racial and ethnic distributions, and social and health disparities. Modern technologies, for both data-gathering and data-analyzing, make this possible at a scale that was previously unachievable. Finally, the psychosocial and economic environment in which pregnancy takes place must be considered to promote the health and wellness of communities worldwide.