Machine learning to predict early recurrence after oesophageal cancer surgery.

BACKGROUND: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. METHODS: Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. RESULTS: A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). CONCLUSION: The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.

ANTECEDENTES: la recidiva precoz del cáncer tras esofaguectomía es un problema frecuente con una incidencia del 20-30% a pesar del uso generalizado del tratamiento neoadyuvante. La cuantificación de este riesgo es difícil y los modelos actuales funcionan mal. Este estudio se propuso desarrollar un modelo predictivo para la recidiva precoz después de la cirugía para el adenocarcinoma de esófago utilizando una gran cohorte multinacional y enfoques con aprendizaje automático. MÉTODOS: Se analizaron pacientes consecutivos sometidos a esofaguectomía por adenocarcinoma y que recibieron tratamiento neoadyuvante en 6 unidades de cirugía esofagogástrica del Reino Unido y 1 de los Países Bajos. Con la utilización de características clínicas y la histopatología postoperatoria se generaron modelos mediante regresión de red elástica (elastic net regression, ELR) y métodos de aprendizaje automático Random Forest (RF) y XG boost (XGB). Finalmente, se generó un modelo combinado (Ensemble) de dichos métodos. La importancia relativa de los factores respecto al resultado se calculó como porcentaje de contribución al modelo. RESULTADOS: En total se incluyeron 812 pacientes. La tasa de recidiva a menos de 1 año fue del 29,1%. Todos los modelos demostraron una buena discriminación. Las áreas bajo la curva ROC (AUC) validadas internamente fueron similares, con el modelo Ensemble funcionando mejor (ELR = 0,791, RF = 0,801, XGB = 0,804, Ensemble = 0,805). El rendimiento fue similar cuando se utilizaba validación interna-externa (validación entre centros, Ensemble AUC = 0,804). En el modelo final, las variables más importantes fueron el número de ganglios linfáticos positivos (25,7%) y la invasión linfovascular (16,9%). CONCLUSIÓN: El modelo derivado con la utilización de aproximaciones con aprendizaje automático y un conjunto de datos internacional proporcionó un rendimiento excelente para cuantificar el riesgo de recidiva precoz tras la cirugía y será útil para clínicos y pacientes a la hora de establecer un pronóstico.

Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma.

BACKGROUND: This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. METHODS: A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. RESULTS: TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1-2; median overall survival (OS) not reached) and non-responders (TRG 3-5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non-responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). CONCLUSION: A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1-2. Among local non-responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders.

Defining a positive circumferential resection margin in oesophageal cancer and its implications for adjuvant treatment.

BACKGROUND: A positive circumferential resection margin (CRM) has been associated with a poorer prognosis in oesophageal and oesophagogastric junctional (OGJ) cancer. The College of American Pathologists defines the CRM as positive if tumour cells are present at the margin, whereas the Royal College of Pathologists also include tumour cells within 1 mm of this margin. The relevance of these differences is not clear and no study has investigated the impact of adjuvant therapy. The aim was to identify the optimal definition of an involved CRM in patients undergoing resection for oesophageal or OGJ cancer, and to determine whether adjuvant radiotherapy improved survival in patients with an involved CRM. METHODS: This was a single-centre retrospective study of patients who had undergone attempted curative resection for a pathological T3 oesophageal or OGJ cancer. Clinicopathological variables and distance from the tumour to the CRM, measured to ± 0.1 mm, were correlated with survival. RESULTS: A total of 226 patients were included. Sex (P = 0·018), tumour differentiation (P = 0·019), lymph node status (P < 0·001), number of positive nodes (P < 0·001), and CRM distance (P = 0·042) were independently predictive of prognosis. No significant survival difference was observed between positive CRM 0-mm and 0·1-0·9-mm groups after controlling for other prognostic variables. Both groups had poorer survival than matched patients with a CRM at least 1 mm clear of tumour cells. Among patients with a positive CRM of less than 1 mm, those undergoing observation alone had a median survival of 18·6 months, whereas survival was a median of 10 months longer in patients undergoing adjuvant radiotherapy, but otherwise matched for prognostic variables (P = 0·009). CONCLUSION: A positive CRM of 1 mm or less should be regarded as involved. Adjuvant radiotherapy confers a significant survival benefit in selected patients with an involved CRM.

Minimising recurrence after primary femoral hernia repair; is mesh mandatory?

PURPOSE: The recent international hernia guidelines advocate laparoscopic pre-peritoneal mesh repair for primary femoral hernias. However, no randomised trial has demonstrated a lower recurrence rate compared to suture repair. This study aimed to determine the 5-year recurrence rate following femoral hernia repair, in elective and emergency settings, according to surgical approach (open or laparoscopic) and method (suture, suture + mesh, or mesh alone). METHODS: Consecutive patients undergoing primary femoral hernia repairs within a single health board, between 2007 and 2013, were identified from a prospective audit. Patients who had died or were uncontactable during the period of follow-up were excluded. Recurrence was defined as the clinical suspicion of an ipsilateral groin hernia at outpatient review or patient reported ipsilateral groin swelling. RESULTS: A total of 297 patients underwent primary femoral hernia repairs in the time period. Of the 138 cases with complete follow-up, 25 patients experienced recurrence at 5 years (18%), with 60% of recurrences evident within the first post-operative year. The median follow-up of the remaining 113 patients was 93 months (range 63-127). No difference could be detected in recurrence rates (P = 0.372, P = 0.353), or time to recurrence (P = 0.421, P = 0.295), according to repair type (suture only, suture and mesh, or mesh only) or surgical approach (high open, low open and laparoscopic pre-peritoneal), respectively. CONCLUSIONS: Use of different surgical approaches and types of repair for primary presentations of femoral hernia did not affect the recurrence rate or time to recurrence. Use of a pre-peritoneal mesh did not alter the recurrence rate or recurrence free survival, in either elective or emergency settings, compared to simple suture repair. Recurrence following primary femoral hernia repair tends to occur within the first post-operative year, suggesting that technical factors may be as important as suture or mesh failure.

After-school interventions to increase physical activity among youth.

Most children and adolescents do not meet the recommended 60 minutes or more of moderate to vigorous physical activity per day. One attractive approach to increasing physical activity in young people is providing activity through structured after-school programmes. This paper provides a review of the scientific literature on the effects of after-school programmes on physical activity in children and adolescents. After-school physical activity interventions provided mixed results; some increased children's physical activity, others did not. Although after-school programmes have the potential to help children and adolescents engage in regular, enjoyable physical activity, the research on these programmes is limited and, in some cases, methodologically weak. Additional, well-controlled studies are needed to identify the components of after-school programmes that promote physical activity and to determine the level of activity that can be attained when children and adolescents participate in these programmes.

Walking and running to benefit breast cancer: descriptive characteristics of participants in the 2017 Walk for Life events.

AIMS: The prevalence of charities and other non-profit organisations sponsoring for-cause physical activity (PA) events has continued to rise. Few studies have examined for-cause events through a public health perspective to determine the reach and potential for public health and PA promotion. This study described participants in a for-cause event supporting breast cancer to determine the reach of the event and identified possible leverage points of for-cause events for public health promotion. METHODS: Participants registered online for the Walk for Life events in Columbia, SC (Half marathon, 10k, 5k, and Walk-a-thon), were included in this study. Data were analyzed using Microsoft Excel. RESULTS: Over 6,000 people participated in the event and 4,942 registered online. Of online registrants, most participants were women (n = 3,800, 78.95%) and most participants, completed the walk-a-thon (n = 3,539), followed by the 5k (n = 829), half-marathon (n = 236), and 10k (n = 209). The average age of participants was 39.79 years (SD = 1.35). CONCLUSIONS: For-cause PA events often recruit high numbers of participants, particularly high-priority populations in PA interventions. Therefore, these events bear innovative implications for PA researchers and practitioners to leverage these events to promote health and PA while simultaneously supporting charity and non-profit organisations.

Moderate-to-vigorous physical activity is associated with decreases in body mass index from ages 9 to 15 years.

OBJECTIVE: The purpose of this study is to determine whether time spent in objectively measured physical activity is associated with change in body mass index (BMI) from ages 9 to 15. DESIGN AND METHODS: The participants were enrolled in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (n = 938). At ages 9, 11, 12, and 15 the time spent in moderate-to-vigorous physical activity (MVPA) was objectively measured, and BMI was calculated (kg/m(2) ). Longitudinal quantile regression was used to analyze the data. The 10th, 25th, 50th, 75th, and 90th BMI percentiles were modeled as the dependent variables with age and MVPA (h/day) modeled as predictors. Adjustment was also made for gender, race, sleep, healthy eating score, maternal education, and sedentary behavior. RESULTS: A negative association between MVPA and change in BMI was observed at the 90th BMI percentile (-3.57, 95% CI -5.15 to -1.99 kg/m(2) per hour of MVPA). The negative association between time spent in MVPA and change in BMI was progressively weaker toward the 10th BMI percentile (-0.27, 95% CI -0.62 to 0.07 kg/m(2) per hour of MVPA). The associations remained similar after adjusting for the covariates, and when the analyses were stratified by gender. CONCLUSION: Time spent in MVPA was negatively associated with change in BMI from age 9 to 15. The association was strongest at the upper tail of the BMI distribution, and increasing time spent in MVPA could help reduce the prevalence of childhood obesity.

Factors associated with development of excessive fatness in children and adolescents: a review of prospective studies.

The purpose of this review was to examine the factors that predict the development of excessive fatness in children and adolescents. Medline, Web of Science and PubMed were searched to identify prospective cohort studies that evaluated the association between several variables (e.g. physical activity, sedentary behaviour, dietary intake and genetic, physiological, social cognitive, family and peer, school and community factors) and the development of excessive fatness in children and adolescents (5-18 years). Sixty-one studies met the eligibility criteria and were included. There is evidence to support the association between genetic factors and low physical activity with excessive fatness in children and adolescents. Current studies yielded mixed evidence for the contribution of sedentary behaviour, dietary intake, physiological biomarkers, family factors and the community physical activity environment. No conclusions could be drawn about social cognitive factors, peer factors, school nutrition and physical activity environments, and the community nutrition environment. There is a dearth of longitudinal evidence that examines specific factors contributing to the development of excessive fatness in childhood and adolescence. Given that childhood obesity is a worldwide public health concern, the field can benefit from large-scale, long-term prospective studies that use state-of-the-art measures in a diverse sample of children and adolescents.

MRI scanning and orthodontics.

Magnetic Resonance Imaging (MRI) plays an important role in diagnosis for many head and neck lesions. Both clinical and experimental studies have shown that orthodontic appliances may produce image distortion on MRI scans of the head and neck. A case is presented in which the patient complained of unexplained right-sided facial paraesthesia, whilst undergoing fixed appliance orthodontic treatment. This was a serious symptom, which warranted investigation including a MRI scan. The compatibility of fixed appliances with MRI is discussed.

Distal end cutters--efficiency, safety and design.

This investigation aimed to evaluate the efficiency of a range of different distal end cutters in cutting and holding the ends of orthodontic arch wires. Fourteen different types of distal end cutter were used to cut a range of orthodontic arch wires under standard conditions. The arch wires comprised nickel-titanium and stainless steel wires of different dimensions, as well as twist flex and coaxial wires. The number of times each wire was successfully cut and held by each cutter was recorded. Significant differences in performance between the cutters were noted, particularly in holding the cut distal ends. Small diameter nickel-titanium wires were significantly less well held than heavier grade or stainless steel wires. Twist flex and coaxial wires were less easily cut cleanly than nickel-titanium and plain stainless steel wires.

Acquisition of hyaluronate-binding affinity in vivo by newly synthesized cartilage proteoglycans.

We have studied the hyaluronate-binding properties of aggregating cartilage proteoglycans synthesized in vivo by immature (6-week), mature (25-week) and aged (75-week) rabbits. Precursor isotope (35SO4) was given by intra-articular injection and articular cartilage was removed from rabbits after periods ranging from 1.5 h to 168 h. Proteoglycans were extracted with 4 M-guanidinium/HCl and monomers were isolated by CsCl gradient centrifugation under dissociative conditions. The percentages of both radiolabelled and total tissue monomers with a high affinity for hyaluronate [that is, capable of forming aggregates on Sepharose CL-2B in the presence of 0.8% (w/w) hyaluronate] were then determined. For all samples about 30% of the tissue monomers were high-affinity; however, less than 5% of the radiolabelled monomers were high-affinity at 1.5 h after injection, and this figure increased gradually with time in vivo. The increase was rapid in immature rabbits, such that after 24 h, about 30% of the radiolabelled monomers were high-affinity; on the other hand for mature and aged rabbits the increase was markedly slower such that 30% high-affinity was attained only after about 72 h. The results show that aggregating cartilage proteoglycans are secreted in vivo in a 'precursor' form with a low affinity for hyaluronate, and suggest that conversion of these monomers to a form with a higher binding affinity occurs with a half-time of about 12 h in immature cartilages but greater than 24 h in mature cartilages. The possible relationship of these findings to the process of proteoglycan aggregation in vivo is discussed.