Local Excision for organ preservation in early REctal cancer with No Adjuvant treatment (LORENA Trial): prospective observational study protocol.

INTRODUCTION: Local resection (LR) is an alternative to total mesorectal excision (TME) that avoids its associated morbidity to the detriment of oncological radicality in early stages of rectal cancer. There are several conditioning factors for the success of this strategy, such as poor prognosis histological factors (PPHF), involvement of resection margins, clinical under staging, or complications that may lead to the indication for radical surgery with TME. PATIENTS AND METHOD: An international multicenter prospective observational open-label study has been designed. Consecutive patients diagnosed with early rectal cancer (cT1N0 on MRI + / - endorectal ultrasound) whose lower limit is a maximum of 2 cm proximal to the ano-rectal junction will be included. The primary objective of the study is to determine the overall prevalence of PPHF after LR and requiring TME or postoperative radio-chemotherapy. DISCUSSION: The prevalence of PPHF conditioning the success of LR in early distal rectal cancer has been scarcely studied in the literature, and there are very few prospective data. Considering the increasing interest in the watch and wait strategy in rectal cancer and its possible application in early-stage tumors, it seems necessary to know this information. The results of this study will help guide clinical practice in patients with early distal rectal cancer. It will also provide quality information for the design of future comparative studies to improve organ preservation success in these patients. TRIAL REGISTRATION NUMBER: NCT05927584.

An International Expert-Based Consensus on the Definition of a Clinical Near-Complete Response After Neoadjuvant (Chemo)radiotherapy for Rectal Cancer.

BACKGROUND: A variety of definitions for a clinical near-complete response after neoadjuvant (chemo) radiotherapy for rectal cancer are currently used. This variety leads to inconsistency in clinical practice, long-term outcome, and trial enrollment. OBJECTIVE: The aim of this study was to reach expert-based consensus on the definition of a clinical near-complete response after (chemo) radiotherapy. DESIGN: A modified Delphi process, including a systematic review, 3 surveys, and 2 meetings, was performed with an international expert panel consisting of 7 surgeons and 4 radiologists. The surveys consisted of individual features, statements, and feature combinations (endoscopy, T2-weighted MRI, and diffusion-weighted MRI). SETTING: The modified Delphi process was performed in an online setting; all 3 surveys were completed online by the expert panel, and both meetings were hosted online. MAIN OUTCOME MEASURES: The main outcome was to reach consensus (80% or more agreement). RESULTS: The expert panel reached consensus on a 3-tier categorization of the near-complete response category based on the likelihood of the response to evolve into a clinical complete response after a longer waiting interval. The panelists agreed that a near-complete response is a temporary entity only to be used in the first 6 months after (chemo)radiotherapy. Furthermore, consensus was reached that the lymph node status should be considered when deciding on a near-complete response and that biopsies are not always needed when a near-complete response is found. No consensus was reached on whether primary staging characteristics have to be taken into account when deciding on a near-complete response. LIMITATIONS: This 3-tier subcategorization is expert-based; therefore, there is no supporting evidence for this subcategorization. Also, it is unclear whether this subcategorization can be generalized into clinical practice. CONCLUSIONS: Consensus was reached on the use of a 3-tier categorization of a near-complete response, which can be helpful in daily practice as guidance for treatment and to inform patients with a near-complete response on the likelihood of successful organ preservation. See Video Abstract. UN CONSENSO INTERNACIONAL BASADO EN EXPERTOS ACERCA DE LA DEFINICIN DE UNA RESPUESTA CLNICA CASI COMPLETA DESPUS DE QUIMIORADIOTERAPIA NEOADYUVANTE CONTRA EL CNCER DE RECTO: ANTECEDENTES:Actualmente, se utilizan una variedad de definiciones para una respuesta clínica casi completa después de quimioradioterapia neoadyuvante contra el cáncer de recto. Esta variedad resulta en inconsistencia en la práctica clínica, los resultados a largo plazo y la inscripción en ensayos.OBJETIVO:El objetivo de este estudio fue llegar a un consenso de expertos sobre la definición de una respuesta clínica casi completa después de quimioradioterapia.DISEÑO:Se realizó un proceso Delphi modificado que incluyó una revisión sistemática, 3 encuestas y 2 reuniones con un panel internacional de expertos compuesto por siete cirujanos y 4 radiólogos. Las encuestas consistieron en características individuales, declaraciones y combinaciones de características (endoscopía, T2W-MRI y DWI).AJUSTE:El proceso Delphi modificado se realizó en un entorno en línea; el panel de expertos completó las tres encuestas en línea y ambas reuniones se realizaron en línea.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue llegar a un consenso (≥80% de acuerdo).RESULTADOS:El panel de expertos llegó a un consenso sobre una categorización de tres niveles de la categoría de respuesta casi completa basada en la probabilidad de que la respuesta evolucione hacia una respuesta clínica completa después de un intervalo de espera más largo. Los panelistas coincidieron en que una respuesta casi completa es una entidad temporal que sólo debe utilizarse en los primeros 6 meses después de la quimioradioterapia. Además, se llegó a un consenso en que se debe considerar el estado de los nódulos linfáticos al decidir sobre una respuesta casi completa y que no siempre se necesitan biopsias cuando se encuentra una respuesta casi completa. No se llegó a un consenso sobre si se deben tener en cuenta las características primarias de estadificación al decidir una respuesta casi completa.LIMITACIONES:Esta subcategorización de 3 niveles está basada en expertos; por lo tanto, no hay evidencia que respalde esta subcategorización. Además, no está claro si esta subcategorización puede generalizarse a la práctica clínica.CONCLUSIONES:Se alcanzó consenso sobre el uso de una categorización de 3 niveles de una respuesta casi completa que puede ser útil en la práctica diaria como guía para el tratamiento y para informar a los pacientes con una respuesta casi completa sobre la probabilidad de una preservación exitosa del órgano. (Traducción - Dr. Aurian Garcia Gonzalez).

Dynamic local mRNA localization and translation occurs during the postnatal molecular maturation of perivascular astrocytic processes.

Astrocytes are highly ramified and send out perivascular processes (PvAPs) that entirely sheathe the brain's blood vessels. PvAPs are equipped with an enriched molecular repertoire that sustains astrocytic regulatory functions at the vascular interface. In the mouse, PvAP development starts after birth and is essentially complete by postnatal day (P) 15. Progressive molecular maturation also occurs over this period, with the acquisition of proteins enriched in PvAPs. The mechanisms controlling the development and molecular maturation of PvAPs have not been extensively characterized. We reported previously that mRNAs are distributed unequally in mature PvAPs and are locally translated. Since dynamic mRNA localization and local translation influence the cell's polarity, we hypothesized that they might sustain the postnatal maturation of PvAPs. Here, we used a combination of molecular biology and imaging approaches to demonstrate that the development of PvAPs is accompanied by the transport of mRNA and polysomal mRNA into PvAPs, the development of a rough endoplasmic reticulum (RER) network and Golgi cisternae, and local translation. By focusing on genes and proteins that are selectively or specifically expressed in astrocytes, we characterized the developmental profile of mRNAs, polysomal mRNAs and proteins in PvAPs from P5 to P60. We found that some polysomal mRNAs polarized progressively towards the PvAPs. Lastly, we found that expression and localization of mRNAs in developing PvAPs is perturbed in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts. Our results indicate that dynamic mRNA localization and local translation influence the postnatal maturation of PvAPs.

International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy.

PURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (ISB) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to ISB. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between ISB and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P = .0004). ISB was also significantly associated with disease-free survival (log-rank P = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P = .0017). The addition of ISB to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.

Local Regrowth and the Risk of Distant Metastases Among Patients Undergoing Watch-and-Wait for Rectal Cancer: What Is the Best Control Group? Multicenter Retrospective Study.

BACKGROUND: A proportion of rectal cancer patients who achieve a clinical complete response may develop local regrowth. Although salvage appears to provide appropriate local control, the risk of distant metastases is less known. OBJECTIVE: To compare the risk of distant metastases between patients who achieve a clinical complete response (watch-and-wait strategy) and subsequent local regrowth and patients managed by surgery after chemoradiation. DESIGN: Retrospective multicenter cohort study. SETTINGS: This study used data of patients from 3 institutions who were treated between 1993 and 2019. PATIENTS: Patients with initial clinical complete response (after neoadjuvant therapy) followed by local regrowth and patients with near-complete pathological response (≤10%) after straightforward surgery after chemoradiation were included. MAIN OUTCOME MEASURES: Univariate and multivariate analyses were performed to identify risk factors for distant metastases. Kaplan-Meier curves were created (log-rank test) to compare survival outcomes. Analyses were performed using time zero as last day of radiation therapy or as date of salvage resection in the local regrowth group. RESULTS: Twenty-one of 79 patients with local regrowth developed distant metastases, whereas only 10 of 74 after upfront total mesorectal excision following neoadjuvant chemoradiation therapy ( p = 0.04). Local regrowth and final pathology (ypT3-4) were the only independent risk factors associated with distant metastases. When using date of salvage resection as time zero, distant metastases-free survival rates were significantly inferior for patients with local regrowth (70% vs 86%; p = 0.01). LIMITATIONS: Small number of patients, many neoadjuvant therapies, and selection bias. CONCLUSIONS: Patients undergoing watch-and-wait strategy who develop local regrowth are at higher risk for development of distant metastases compared to patients with near-complete pathological response managed by upfront surgery after chemoradiation. See Video Abstract. NUEVO CRECIMIENTO LOCAL Y EL RIESGO DE METSTASIS A DISTANCIA ENTRE PACIENTES SOMETIDOS A OBSERVACIN Y ESPERA POR CNCER DE RECTO CUL ES EL MEJOR GRUPO DE CONTROL ESTUDIO RETROSPECTIVO MUTICNTRICO: ANTECEDENTES:Una proporción de pacientes que logran una respuesta clínica completa pueden desarrollar un nuevo crecimiento local. Si bien el rescate parece proporcionar un control local apropiado, el riesgo de metástasis a distancia es menos conocido.OBJETIVO:Comparar el riesgo de metástasis a distancia entre los pacientes que logran una respuesta clínica completa (estrategia de observación y espera) y el nuevo crecimiento local posterior con los pacientes tratados con cirugía después de la quimiorradiación.DISEÑO:Estudio de cohorte multicéntrico retrospectivo.CONFIGURACIÓN:Este estudio utilizó datos de pacientes de 3 instituciones que fueron tratados entre 1993 y 2019.PACIENTES:Pacientes con respuesta clínica completa inicial (después de la terapia neoadyuvante) seguida de crecimiento local nuevo y pacientes con respuesta patológica casi completa (≤10 %) después de cirugía directa después de quimiorradiación.PRINCIPALES MEDIDAS DE RESULTADO:Se realizó un análisis univariante/multivariante para identificar los factores de riesgo de metástasis a distancia. Se crearon curvas de Kaplan-Meier (prueba de rango logarítmico) para comparar los resultados de supervivencia. El análisis se realizó utilizando el tiempo cero como último día de radioterapia (1) o como fecha de resección de rescate (2) en el grupo de recrecimiento local.RESULTADOS:Veintiuno de 79 pacientes con recrecimiento local desarrollaron metástasis a distancia, mientras que solo 10 de 74 después de una cirugía sencilla (p = 0,04). El recrecimiento local y la patología final (ypT3-4) fueron los únicos factores de riesgo independientes asociados con las metástasis a distancia. Cuando se utilizó la fecha de la resección de rescate como tiempo cero, las tasas de supervivencia sin metástasis a distancia fueron significativamente inferiores para los pacientes con recrecimiento local (70 frente a 86 %; p = 0,01).LIMITACIONES:Pequeño número de pacientes, muchas terapias neoadyuvantes, sesgo de selección.CONCLUSIONES:Los pacientes sometidos a observación y espera que desarrollan un nuevo crecimiento local tienen un mayor riesgo de desarrollar metástasis a distancia en comparación con los pacientes con una respuesta patológica casi completa manejados con cirugía por adelantado después de la quimiorradiación. (Traducción-Dr. Xavier Delgadillo ).

Confiabilidad Inter-evaluador en la Medición del Grosor Muscular y el Ángulo de Penación a través de la Evaluación Ecográfica: Estudio entre un Experto y un Kinesiólogo en Formación / Inter-Evaluator Reliability in Measurement of Muscle Thickness and Penance Angle through Ultrasound Evaluation: Comparison Study between an Expert and a Physical Therapist in Training

Existen diversas formas de evaluar el músculo esquelético. Una herramienta que ha ganado relevancia es la evaluación ecográfica. Esta, permite medir el grosor muscular (GM) y el ángulo de penación (AP). Por otra parte, en la formación inicial de los Kinesiólogos es importante realizar el ejercicio de la confiabilidad en la medición en relación al experto. un procedimiento diagnóstico. Así, el objetivo de este estudio es determinar la confiabilidad inter-evaluador en la medición del GM y el AP, a través de la evaluación ecográfica, entre un experto y un kinesiólogo en formación. La capacitación contó de tres fases; el ciclo teórico, el ciclo práctico y el proceso de confiabilidad. Para este último, se realizaron 10 pruebas para cada una de las mediciones GM 1, GM 2 y GM 3 y de AP. La confiabilidad inter-evaluador en la medición de GM es buena a excelente en los tres intentos GM1 (ICC=0,81; p=0,001), GM2 (ICC=0,86; p<0,001), GM3 (ICC=0,88;<0,001). Por su parte, la confiabilidad del AP fue pobre a regular (ICC=0,21; p=0,143. Las conclusiones de esta investigación indican que existe una excelente confiabilidad inter evaluador en la medición de GM. No así, en la medición de AP, por lo que se sugiere incrementar las horas prácticas en el proceso de aprendizaje de esta medida.

SUMMARY: Skeletal muscle can be assessed in a number of different ways. Consequently, ultrasound evaluation has become a relevant diagnostic tool. This procedure allows measuring muscle thickness (MT) and pennation angle (PA). Furthermore, during the initial training of physical therapists it is important in a diagnostic procedure, to exercise reliability in measurement in comparison to the expert. Therefore, the objective of this study is to determine the inter-rater reliability in the measurement of MT and PA, through ultrasound evaluation, between an expert and a physical therapist in training. This training was comprised of three phases: The theoretical cycle, the practical cycle and the reliability process. For the latter, ten different tests were performed for each of the MT 1, MT 2 and MT 3 and PA measurements. Inter-rater reliability in the MT measurement was good to excellent in the three attempts MT1 (ICC=0.81; p=0.001), MT2 (ICC=0.86; p<0.001), MT3 (ICC=0. 88;<0.001). On the other hand, reliability of the PA was poor to fair (ICC=0.21; p=0.143. In conclusion, this research indicates that there is excellent inter-rater reliability in the measurement of MT. This does not however apply to the measurement of PA. It is therefore suggested that practical hours during the learning process of this measure be increased.

Disección carotídea espontánea: Presentación de un caso clínico con revisión de la literatura / Carotid Artery Dissection. Case Report and Literature Review

Resumen Introducción: La disección carotídea consiste en el desgarro de la pared del vaso. Es una patología infrecuente, pero es la causa más común de enfermedad vascular cerebral (EVC) isquémica en personas menores de 45 años. Las manifestaciones clínicas son muy variables. Método: Utilizamos las recomendaciones CARE para el reporte de casos clínicos. Caso clínico: Hombre de 45 años previamente sano, con debilidad aguda de la extremidad torácica derecha sin causa aparente. La tomografía simple de cráneo no evidenció alteraciones. La resonancia magnética mostró una oclusión completa de la arteria carótida interna en todos sus segmentos y disminución del flujo de la arteria cerebral media izquierda. La evolución clínica fue desfavorable. Conclusión: La disección carotídea debe sospecharse en personas con EVC sin factores de riesgo cardiovascular.

Abstract Introduction: Carotid dissection consists of a tear in the vessel wall. It is a rare pathology, but it is the most common cause of ischemic cerebral vascular disease (CVD) in people under 45 years of age. The clinical manifestations are very variable. Method: We used CARE recommendations for reporting clinical cases. Clinical case: Previously, a healthy 45-year-old man with acute weakness of the right thoracic extremity without apparent cause. The simple skull tomography did not show any alterations. MRI showed complete occlusion of the internal carotid artery in all its segments and decreased flow of the left middle cerebral artery. The clinical evolution was unfavorable. Conclusion: Carotid dissection should be suspected in people with CVD without cardiovascular risk factors.

Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients.

BACKGROUND: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. METHODS: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1). RESULTS: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). CONCLUSION: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.

Benefits of Using Magnetic Resonance Imaging During Breast Tissue Expansion: Literature Review and Case Series.

Breast cancer results in up to 1.6 million new candidates for yearly breast reconstruction (BR) surgery. Two-stage breast reconstruction surgery with the use of a tissue expander (TE) is a common approach to reconstructing the breast after mastectomy. However, a common disadvantage encountered with the traditional breast TE is the magnetic injection port, which has been reported to cause injuries in patients undergoing magnetic resonance (MR) imaging. Therefore this type of breast TE is labeled "MR unsafe." Recent technological advances have incorporated radio-frequency identification (RFID) technology in the TE to allow for the location of the injection port without magnetic components, resulting in an MR-conditional TE. This paper aims to review the information regarding the safety profile of TEs with magnetic ports and to gather distinct clinical scenarios in which an MR-conditional TE benefits the patient during the BR process. A literature review ranging from 2018 to 2022 was performed with the search terms: "tissue expander" OR "breast tissue expander" AND "magnetic resonance imaging" OR "MRI." Additionally, a case series was collected from each of the authors' practices. The literature search yielded 13 recent peer-reviewed papers, and 6 distinct clinical scenarios were compiled and discussed. Most clinicians find MRI examinations to be the state-of-art diagnostic imaging modality. However, due to the preexisting risks associated with TEs with magnetic ports, the MRI labeling classification should be considered when deciding which TE is the most appropriate for the patient requiring MRI examinations.

Asociación entre la Arquitectura Muscular y el Índice de Calidad Muscular en Adultos Sedentarios / Association Between Muscle Architecture and Muscle Quality Index in Sedentary Adults

La evaluación de la calidad y la arquitectura muscular son importantes para comprender y cuantificar los cambios musculares asociados con el envejecimiento y el estilo de vida sedentario, además nos facilita información de la capacidad del músculo para generar fuerza, potencia o funcionalidad. los objetivos del estudio fueron (I) determinar la asociación entre los parámetros de la arquitectura muscular y el índice de calidad muscular (MQI) y (II) determinar la asociación entre los parámetros de la arquitectura muscular y la potencia media relativa del sit to stand test (STS). Únicamente el grosor muscular (MT) mostró una asociación moderada con el MQI (r = 0,545). En contraste, tanto la longitud del fascículo (FL) como el ángulo de penación (PA) exhibieron asociaciones "muy bajas", las cuales no resultaron significativas con el MQI. Al examinar la relación de los parámetros de la arquitectura muscular con la potencia media relativa de STS, MT presentó una asociación "moderada" (r = 0,444). Sin embargo, tanto FL como PA mostraron asociaciones "muy bajas" y "bajas", respectivamente, con la potencia media relativa al STS. En conclusión, estos hallazgos refuerzan la idea de que MT puede ser un indicador relevante de la calidad muscular y la capacidad de generar potencia en la prueba de STS. Específicamente, se observó que un aumento en MT estaba asociado con una mejora en MQI y la potencia media relativa de STS.

SUMMARY: Assessment of muscle quality and architecture is important for understanding and quantifying muscle changes associated with aging and a sedentary lifestyle and provides information on the muscle's ability to generate strength, power, or function. The aims of the study were (I) to determine the association between muscle architecture parameters and muscle quality index (MQI) and (II) to determine the association between muscle architecture parameters and mean relative power in the sit-to-stand test (STS). Only muscle thickness (MT) showed a moderate association with MQI (r = 0.545). In contrast, both fascicle length (FL) and penile angle (PA) exhibited "very low" associations, which were not significant with the MQI. When examining the relationship between muscle architecture parameters and mean relative STS power, MT presented a "moderate" association (r = 0.444). However, both LF and PA showed "very low" and "low" associations, respectively, with a mean power relative to STS. In conclusion, these findings reinforce the idea that MT may be a relevant indicator of muscle quality and ability to generate power in the STS test. Specifically, an increase in MT was associated with an improvement in MQI and mean power relative to STS.

Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage: Development and Validation of a Prediction Model in a Large International Cohort.

OBJECTIVE: To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL). BACKGROUND: AL after RC resection often results in a permanent stoma. METHODS: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated. RESULTS: This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76). CONCLUSIONS: The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies.

A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait.

BACKGROUND: Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer. METHODS: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival. DISCUSSION: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05000697; registered on August 11th, 2021.

El consumo de bebidas dulces incrementa diferencialmente la expresión de Oxitocina en núcleos hipotalámicos / The consumption of sweet drinks differentially increases the expression of oxytocin in hypothalamic nuclei

Resumen Se reconoce la participación de la oxitocina en el control de la alimentación, pero su mecanismo de acción no se ha establecido totalmente. Por tanto, el objetivo de esta investigación fue evaluar el efecto del acceso intermitente a una solución de sacarosa, sobre la expresión de las neuronas del núcleo paraventricular (PVN) y del núcleo supraótico (SON) que producen oxitocina (Oxt), y caracterizar la microestructura de la conducta de beber en ratas saciadas. Se tuvieron tres grupos de ratas macho Wistar saciadas, y en la primera hora al inicio del periodo de luz, el grupo Control tuvo agua, el grupo Restringido 5g de una solución de sacarosa al 20% y el grupo Ad libitum acceso libre a la solución de sacarosa. Los sujetos incrementaron el consumo de la solución de sacarosa a pesar de estar saciados; debido a la interrupción del estado de saciedad y la demora de la satisfacción. La actividad de las neuronas de Oxt se incrementó en ambos núcleos, en el grupo Restringido la mayor expresión se observó en el SON y en el grupo Ad libitum en el PVN. No se encontró correlación entre la cantidad de bebida ingerida y la actividad de las neuronas Oxt.

Abstract The role of oxytocin in feeding control is recognized, but its mechanism of action has not been fully established. Therefore, the aim of this research was to evaluate the effect of intermittent access to a sucrose solution on the expression of paraventricular nucleus (PVN) and supraotic nucleus (SON) neurons that produce oxytocin (Oxt), and to characterize the microstructure of drinking behavior in satiated rats. Three groups of male Wistar rats satiated were used, and in the first hour at the beginning of the light period, a Control group had water, a Restricted group 5g of a 20% sucrose solution and Ad libitum group with free access to sucrose solution. The experimental subjects increased the consumption of the sucrose solution despite being satiated, due to the interruption of the state of satiety and the delay of the satiation process. Oxt neurons increased their activity in both nuclei, in the Restricted group the highest expression was observed in the SON and in the Ad libitum group in the PVN. No correlation was found between the amount of drink ingested and the activity of Oxt neurons.

Watch and Wait Approach for Rectal Cancer.

The administration of neoadjuvant chemoradiotherapy (nCRT) followed by total mesorrectal excision (TME) and selective use of adjuvant chemotherapy can still be considered the standard of care in locally advanced rectal cancer (LARC). However, avoiding sequelae of TME and entering a narrow follow-up program of watch and wait (W&W), in select cases that achieve a comparable clinical complete response (cCR) to nCRT, is now very attractive to both patients and clinicians. Many advances based on well-designed studies and long-term data coming from big multicenter cohorts have drawn some important conclusions and warnings regarding this strategy. In order to safely implement W&W, it is important consider proper selection of cases, best treatment options, surveillance strategy and the attitudes towards near complete responses or even tumor regrowth. The present review offers a comprehensive overview of W&W strategy from its origins to the most current literature, from a practical point of view focused on daily clinical practice, without losing sight of the most important future prospects in this area.