Enhanced stress-resilience training for surgical trainees.

INTRODUCTION: Core surgical training programmes are associated with a high risk of burnout. This study aimed to assess the influence of a novel enhanced stress-resilience training (ESRT) course delivered at the start of core surgical training in a single UK statutory education body. METHOD: All newly appointed core surgical trainees (CSTs) were invited to participate in a 5-week ESRT course teaching mindfulness-based exercises to develop tools to deal with stress at work and burnout. The primary aim was to assess the feasibility of this course; secondary outcomes were to assess degree of burnout measured using Maslach Burnout Inventory (MBI) scoring. RESULTS: Of 43 boot camp attendees, 38 trainees completed questionnaires, with 24 choosing to participate in ESRT (63.2 per cent; male 13, female 11, median age 28 years). Qualitative data reflected challenges delivering ESRT because of arduous and inflexible clinical on-call rotas, time pressures related to academic curriculum demands and the concurrent COVID-19 pandemic (10 of 24 drop-out). Despite these challenges, 22 (91.7 per cent) considered the course valuable and there was unanimous support for programme development. Of the 14 trainees who completed the ESRT course, nine (64.3 per cent) continued to use the techniques in daily clinical work. Burnout was identified in 23 trainees (60.5 per cent) with no evident difference in baseline MBI scores between participants (median 4 (range 0-11) versus 5 (1-11), P = 0.770). High stress states were significantly less likely, and mindfulness significantly higher in the intervention group (P < 0.010); MBI scores were comparable before and after ESRT in the intervention cohort (P = 0.630, median 4 (range 0-11) versus 4 (1-10)). DISCUSSION: Despite arduous emergency COVID rotas ESRT was feasible and, combined with protected time for trainees to engage, deserves further research to determine medium-term efficacy.

Predictive value of Altmetric score on citation rates and bibliometric impact.

BACKGROUND: Bibliometric and Altmetric analyses provide different perspectives regarding research impact. This study aimed to determine whether Altmetric score was associated with citation rate independent of established bibliometrics. METHODS: Citations related to a previous cohort of 100 most cited articles in surgery were collected and a 3-year interval citation gain calculated. Citation count, citation rate index, Altmetric score, 5-year impact factor, and Oxford Centre for Evidence-Based Medicine levels were used to estimate citation rate prospect. RESULTS: The median interval citation gain was 161 (i.q.r. 83-281); 74 and 62 articles had an increase in citation rate index (median increase 2.8 (i.q.r. -0.1 to 7.7)) and Altmetric score (median increase 3 (0-4)) respectively. Receiver operating characteristic (ROC) curve analysis revealed that citation rate index (area under the curve (AUC) 0.86, 95 per cent c.i. 0.79 to 0.93; P < 0.001) and Altmetric score (AUC 0.65, 0.55 to 0.76; P = 0.008) were associated with higher interval citation gain. An Altmetric score critical threshold of 2 or more was associated with a better interval citation gain when dichotomized at the interval citation gain median (odds ratio (OR) 4.94, 95 per cent c.i. 1.99 to 12.26; P = 0.001) or upper quartile (OR 4.13, 1.60 to 10.66; P = 0.003). Multivariable analysis revealed only citation rate index to be independently associated with interval citation gain when dichotomized at the median (OR 18.22, 6.70 to 49.55; P < 0.001) or upper quartile (OR 19.30, 4.23 to 88.15; P < 0.001). CONCLUSION: Citation rate index and Altmetric score appear to be important predictors of interval citation gain, and better at predicting future citations than the historical and established impact factor and Oxford Centre for Evidence-Based Medicine quality descriptors.

Physiological performance and inflammatory markers as indicators of complications after oesophageal cancer surgery.

BACKGROUND: The extent to which physiological factors influence outcome following oesophageal cancer surgery is poorly understood. This study aimed to evaluate the extent to which cardiorespiratory fitness and selected metabolic factors predicted complications after surgery for carcinoma. METHODS: Two hundred and twenty-five consecutive patients underwent preoperative cardiopulmonary exercise testing to determine peak oxygen uptake ( V ˙ o2peak ), anaerobic threshold and the ventilatory equivalent for carbon dioxide ( V ˙ e/ V ˙ co2 ). Cephalic venous blood was assayed for serum C-reactive protein (CRP) and albumin levels, and a full blood count was done. The primary outcome measure was the Morbidity Severity Score (MSS). RESULTS: One hundred and ninety-eight patients had anatomical resection. A high MSS (Clavien-Dindo grade III or above) was found in 48 patients (24·2 per cent) and was related to an increased CRP concentration (area under the receiver operating characteristic (ROC) curve (AUC) 0·62, P = 0·001) and lower V ˙ o2peak (AUC 0·36, P = 0·003). Dichotomization of CRP levels (above 10 mg/l) and V ˙ o2peak (below 18·6 ml per kg per min) yielded adjusted odds ratios (ORs) for a high MSS of 2·86 (P = 0·025) and 2·92 (P = 0·002) respectively. Compared with a cohort with a low Combined Inflammatory and Physiology Score (CIPS), the OR was 1·70 (95 per cent c.i. 0·85 to 3·39) for intermediate and 27·47 (3·12 to 241·69) for high CIPS (P < 0·001). CONCLUSION: CRP and V ˙ o2peak were independently associated with major complications after potentially curative oesophagectomy for cancer. A composite risk score identified a group of patients with a high risk of developing complications.

ANTECEDENTES: El grado en el que los factores fisiológicos influyen en el resultado tras la cirugía del cáncer de esófago no se conoce bien. Este estudio tuvo como objetivo evaluar en qué medida el estado cardiorrespiratorio y los factores metabólicos seleccionados predecían complicaciones después de cirugía por cáncer. MÉTODOS: Pacientes consecutivos fueron sometidos a una prueba de ejercicio cardiopulmonar preoperatoria para determinar el consumo pico de oxígeno (peak oxygen uptake, V ̇ O2Peak ), el umbral anaeróbico (anaerobic threshold, AT) y el equivalente ventilatorio de dióxido de carbono (ventilatory equivalent for carbon dioxide, V ̇ E / V ̇ CO2 ). Se extrajo sangre de la vena cefálica para analizar la proteína C reactiva (C-reactive protein, CRP) sérica, albumina y hemograma completo. La medida de resultado primario fue la puntuación de la gravedad de la morbilidad (Morbidity Severity Score, MSS). RESULTADOS: Se observó MSS (Clavien-Dindo > 2) en 33 (17,7%) pacientes, relacionándose con CRP elevada (AUC 0,69, P = 0,001) y V ̇O2Peak baja (AUC 0,33, P = 0,003). La dicotomización de la CRP (por encima de 10 mg/L) y V ̇O2Peak (por debajo de 18,6 mL/kg/min) se asociada a una razón de oportunidades (odds ratio, OR) de 4,01 (P = 0,002) y 3,74 (P = 0,002) para MSS y CD > 2, respectivamente. En comparación con la cohorte con una puntuación combinada inflamatoria y fisiológica (Combined Inflammatory and Physiology Score, CIPS) baja, el OR fue de 1,70 (i.c. del 95% 0,85-3,39) para una CIPS intermedia y de 27,47 (3,12-241,69, P < 0,001) para CIPS elevada. CONCLUSIÓN: CRP y V ̇O2Peak se asociaron de forma independiente con complicaciones mayores tras esofaguectomía potencialmente curativa por cáncer. Una puntuación combinada de riesgo identificó a un grupo de pacientes con un riesgo elevado de desarrollar complicaciones.

Surgical training rotation design: effects of hospital type, rotation theme and duration.

BACKGROUND: Entrants into UK surgical specialty training undertake a 2-year programme of core surgical training, rotating through specialties for varying lengths of time, at different hospitals, to gain breadth of experience. This study aimed to assess whether these variables influenced core surgical trainee (CST) work productivity. METHODS: Intercollegiate Surgical Curriculum Programme portfolios of consecutive CSTs between 2016 and 2019 were examined. Primary outcome measures were workplace-based assessment (WBA) completion, operative experience and academic outputs (presentations to learned societies, publications and audits). RESULTS: A total of 344 rotations by 111 CSTs were included. Incremental increases in attainment were observed related to the duration of core surgical training rotation. The median number of consultant-validated WBAs completed during core surgical training were 48 (range 0-189), 54 (10-120) and 75 (6-94) during rotations consisting of 4-, 6- and 12-month posts respectively (P < 0·001). Corresponding median operative caseloads (as primary surgeon) were 84 (range 3-357), 110 (44-394) and 134 (56-366) (P < 0·001) and presentations to learned societies 0 (0-12), 0 (0-14) and 1 (0-5) (P = 0·012) respectively. Hospital type and specialty training theme were unrelated to workplace productivity. Multivariable analysis identified length of hospital rotation as the only factor independently associated with total WBA count (P = 0·001), completion of audit (P = 0·015) and delivery of presentation (P = 0·001) targets. CONCLUSION: Longer rotations with a single educational supervisor, in one training centre, are associated with better workplace productivity. Consideration should be given to this when reconfiguring training programmes within the arena of workforce planning.

ANTECEDENTES: Los residentes de especialidades quirúrgicas del Reino Unido realizan un período troncal de formación quirúrgica de 2 años, en el que rotan por diversas especialidades durante periodos de tiempo variables y en diversos hospitales, a fin de conseguir una experiencia amplia. Este estudio tuvo como objetivo evaluar si estas variables influyeron en la productividad de los residentes durante el período troncal (core surgical trainee, CST). MÉTODOS: Se examinaron los inventarios de los programas del Intercollegiate Surgical Curriculum Programme (ISCP) de CST consecutivos entre 2016 y 2019. Las variables principales fueron la puntuación final del Workplace-Based Assessment (WBA), y la actividad quirúrgica y académica (presentaciones a sociedades académicas, publicaciones y auditorías) realizadas. RESULTADOS: Se incluyeron 344 rotaciones de 111 CST. Se constataron mejores resultados en relación con la duración de la rotación de CST. La mediana (rango) de la puntuación de los supervisores en las WBA fue de 48 (0'189), 54 (10'120) y 75 (6'94) (P < 0,001) en las rotaciones a los 4, 6 y 12 meses, respectivamente. El número de intervenciones (como cirujano principal) fue de 84 (3'357), 110 (44'394) y 134 (56'366) (P < 0,001) y de presentaciones a sociedades científicas fue de 0 (0-12), 0 (0- 14) y 1 (0-5) (P = 0,012). No hubo relación entre el tipo de hospital o la especialidad y la productividad en el lugar de trabajo. El análisis multivariable identificó la duración de la rotación como único factor independientemente relacionado con la puntuación de la WBA (P = 0,001), la finalización de la auditoría (P = 0,015) y el número de presentaciones realizadas (P = 0,001). CONCLUSIÓN: Las rotaciones de periodos de tiempo largos con un solo supervisor y en un solo centro se asocian con una mejor productividad en el lugar de trabajo. Debería tenerse en cuenta este factor al reconfigurar los programas de capacitación desde el punto de vista laboral.

Proof of surgical publication prowess: prospective observational study of factors associated with surrogate markers of academic reach.

BACKGROUND: In the UK, general surgery higher surgical trainees (HSTs) must publish at least three peer-reviewed scientific articles (as first, second or corresponding author) to qualify for certification of completion of training (CCT). This study aimed to identify the factors associated with success in this arena. METHODS: Deanery rosters supplemented with data from the Intercollegiate Surgical Curriculum Programme, PubMed and ResearchGate were used to identify the profiles of consecutive HSTs. Primary outcomes were publication numbers at defined points in higher training (speciality training year (ST) 3-8); secondary outcomes were the Hirsch index and ResearchGate scores. RESULTS: Fifty-nine consecutive HSTs (24 women, 35 men) were studied. The median publication number was 3 (range 0-30). At least three published articles were obtained by 30 HSTs (51 per cent), with 19 (38 per cent) of 50 HSTs achieving this by ST4 (of whom 15 (79 per cent) had undertaken out of programme for research (OOPR) time) and 24 (80 per cent) by ST6. Thirteen HSTs (22 per cent) (ST3, 6; ST4, 4; ST5, 2; ST8, 1) had yet to publish at the time of writing. OOPR was associated with achieving three publications (24 of 35 (69 per cent) versus 6 of 24 (25 per cent) with no formal research time; P = 0·001), higher overall number of publications (median 6 versus 1 respectively; P < 0·001), higher ResearchGate score (median 23·37 versus 5·27; P < 0·001) and higher Hirsch index (median 3 versus 1; P < 0·001). In multivariable analysis, training grade (odds ratio (OR) 1·89, 95 per cent c.i. 0·01 to 3·52; P = 0·045) and OOPR (OR 6·55, 2·04 to 21·04; P = 0·002) were associated with achieving three publications. CONCLUSION: If CCT credentials are to include publication profiles, HST programmes should incorporate research training in workforce planning.

ANTECEDENTES: En el Reino Unido, para obtener el título de especialista (certification of completion of training, CCT), los residentes de cirugía general durante la etapa de formación específica (higher general surgical trainees, HST) deben publicar, al menos, tres artículos científicos en revistas con sistema de revisión por pares (peer review) (como primer o segundo autor o como autor para la correspondencia). Este estudio tuvo como objetivo identificar los factores asociados con el éxito en este aspecto. MÉTODOS: Se identificaron las reseñas de HST consecutivos, mediante datos propios de cada institución y del Intercollegiate Surgical Curriculum Programme, PubMed y ResearchGate. La variable principal fue el número de publicaciones en puntos definidos de la etapa de formación específica (ST3-8); las variables secundarias fueron los índices de Hirsch y las puntuaciones de ResearchGate. RESULTADOS: Se analizó la actividad científica de 59 HST consecutivos (24 mujeres, 35 varones). La mediana del número de publicaciones fue de 3 (rango 0-33). Treinta HST (50,8%) lograron >3 publicaciones; 19 (38,0%) lo lograron en ST4 (78,9% durante el período de investigación al margen del programa de formación quirúrgica (Out of Programme Research (OOPR)), y 24 (80,0% de la totalidad de la cohorte) en ST6. Trece HST (22,0%) no habían publicado ningún trabajo hasta el momento de la redacción de este artículo (6 ST3, 4 ST4, 2 ST5 y 1 ST8). El OOPR se asoció con la consecución de las 3 publicaciones (68,6% versus 25,0%, P = 0,001), con un mayor número de publicaciones (mediana 6 versus 1, P < 0,001), con puntuaciones ResearchGate más elevadas (23,37 versus 5,27, P < 0,001) e índices de Hirsch más altos (3 versus 1, P < 0,001). En el análisis multivariable, el año de residencia (razón de oportunidades, odds ratio, OR 1,890, i.c. del 95% 0,014-3,522, P = 0,045) y el OOPR (OR 6,545, i.c. del 95% 2,037-21,036, P = 0,020) se asociaron con la consecución de las tres publicaciones. CONCLUSIÓN: Si la CCT exige un número de publicaciones, los programas de los HST deberían incorporar formación en investigación dentro de la actividad laboral habitual.

Propensity score regression analysis of oesophageal adenocarcinoma treatment with surgery alone or neoadjuvant chemotherapy.

BACKGROUND: Propensity score (PS) regression analysis can be used to minimize differences between cohorts in order to perform comparisons The aim of this study was to use PS analysis to examine the outcomes of oesophageal adenocarcinoma (OAC) treatment with surgery alone or neoadjuvant chemotherapy (NAC) followed by surgery (NACS), to see whether the benefits seen in a randomized trial (MRC OE02) were reproducible in a UK cancer network clinical practice. METHODS: Consecutive patients undergoing potentially curative treatment for OAC in a regional cancer network were studied. Multiple regression models, including PS analysis, were developed to account for confounding factors. Primary outcome measures were disease-free (DFS) and overall (OS) survival. RESULTS: A cohort of 440 patients was included in a regression analysis controlling for confounders (176 surgery alone, 264 NACS). NACS was associated with a higher positive margin status rate compared with surgery alone (42·4 versus 26·7 per cent respectively; P < 0·001), an inferior 5-year DFS rate (32·1 versus 56·9 per cent; P < 0·001) and a worse 5-year OS rate (27·5 versus 47·3 per cent; P < 0·001). On regression adjustment based on propensity scores, NACS was not associated with DFS (P = 0·220) or OS (P = 0·431). The Mandard tumour regression grade (TRG) score was significantly associated with DFS (hazard ratio (HR) 0·21, 95 per cent c.i. 0·07 to 0·70) and OS (HR 0·27, 0·13 to 0·59). Five-year DFS and OS rates related to TRG were 64 and 62 per cent respectively for 25 good responders versus 8·0 and 8·6 per cent for 127 poor responders (P < 0·001). CONCLUSION: The prescription of NAC to all patients with OAC risks delay in effective treatment of patients who are relatively chemoresistant, given the variability in pathological response. Identification of patients with OAC who may derive the most benefit from NAC should be the focus.

ANTECEDENTES: El análisis de regresión por puntaje de propensión (propensity score, PS) puede ser utilizado para minimizar las diferencias entre cohortes a la hora de hacer comparaciones. El objetivo de este estudio fue utilizar el PS para analizar los resultados del tratamiento del adenocarcinoma de esófago (oesophageal adenocarcinoma, OAC), tanto con cirugia sola (surgery, S) o con quimioterapia neoadyuvante (neoadjuvant chemotherapy, NAC) seguida de cirugía (NACS) para determinar si los beneficios del ensayo aleatorizado MRC OE02 eran reproducibles en la práctica clínica de una red de cáncer del Reino Unido. MÉTODOS: Se estudiaron pacientes consecutivos sometidos a tratamiento potencialmente curativo por OAC en una red de cáncer regional. Se desarrollaron modelos de regresión múltiple, incluyendo PS, para poder ajustar por factores de confusión. Las medidas de resultado primario fueron supervivencia libre de enfermedad (disease-free survival, DFS) y la supervivencia global (overall survival, OS). RESULTADOS: Se incluyó una cohorte de 440 pacientes en un análisis de regresión controlando por factores de confusión (176 S, 264 NACS). NACS se asoció con margen positivo (NACS versus S, 42,4% versus 26,7%, P < 0,001), menor DFS a los 5 años (32,1% versus 56,9, P < 0,001) y peor OS a los 5 años (27,5% versus 47,3%, P < 0,001). En el ajuste de la regresión basada en las puntuaciones de propensión, NACS no se asoció a DFS (P = 0,220) ni a OS (P = 0,431). El grado de regresión tumoral de Mandard (tumour regression grade, TRG) se asoció significativamente con DFS (cociente de riesgos instantáneos, hazard ratio, HR 0,21, i.c. del 95% 0,13-0,59). La DFS y OS a los 5 años en relación con TRG fue 63,6% y 61,5% versus 8,0% y 8,6% (P < 0,001) para buenos y pobres respondedores, respectivamente. CONCLUSIÓN: La indicación de NAC a todos los pacientes con OAC representa un riesgo de demorar un tratamiento efectivo para aquellos pacientes que son relativamente quimiorresistentes, dada la variabilidad en la respuesta patológica. Identificar a los pacientes con OAC que obtendrían el mayor beneficio de la NAC debería centrar el foco de atención.

Neutrophil to lymphocyte ratio as a predictor of response to neoadjuvant chemotherapy and survival in oesophageal adenocarcinoma.

BACKGROUND: Inflammation has an important role in cancer survival, yet whether serum markers of inflammation predict response to potentially curative neoadjuvant chemotherapy (NAC) in oesophageal adenocarcinoma (OAC) is controversial. This study aimed to determine whether the systemic inflammatory response (SIR) is associated with response to NAC and survival. METHODS: Consecutive patients with OAC planned for surgery with curative intent received blood neutrophil and lymphocyte measurements at diagnosis to calculate the neutrophil to lymphocyte ratio (NLR). Pathological variables including pTNM stage, differentiation, vascular invasion and Mandard tumour regression grade (TRG) were recorded. TRGs 1 and 2 were taken to represent a good response, and the primary outcome was overall survival. RESULTS: During follow-up of 136 patients, 36 patients (26·5 per cent) had recurrence and 69 (50·7 per cent) died. Receiver operating characteristic (ROC) curve analysis of NLR before NAC predicted poor TRG (area under the ROC curve 0·71, 95 per cent c.i. 0·58 to 0·83; P = 0·002). In univariable analysis, pT category (P < 0·001), pN category (P < 0·001), poor differentiation (P = 0·006), margin positivity (P = 0·001), poor TRG (P = 0·014) and NLR (dichotomized at 2·25; P = 0·017) were associated with poor overall survival, and NLR retained independent significance in multivariable analysis (hazard ratio 2·26, 95 per cent c.i. 1·03 to 4·93; P = 0·042). CONCLUSION: The pretreatment NLR was associated with a pathological response to NAC and overall survival in patients with OAC. ANTECEDENTES: La inflamación juega un importante papel en la supervivencia por cáncer, aunque aún no se sabe si los marcadores séricos de inflamación predicen la respuesta a la quimioterapia neoadyuvante (neoadjuvant chemotherapy, NAC) potencialmente curativa en el adenocarcinoma de esófago (oesophageal adenocarcinoma, OAC). Este estudio se propuso determinar si la respuesta inflamatoria sistémica (systemic inflammatory response, SIR) estaba asociada con la respuesta a la NAC y a la supervivencia. MÉTODOS: A pacientes consecutivos con OAC en los que se planificó cirugía con intención curativa se les determinó neutrófilos y linfocitos en sangre en el momento del diagnóstico para calcular la tasa neutrófilo-linfocito (neutrophil-lymphocyte ratio, NLR). Se registraron variables patológicas que incluían el estadio pTNM, diferenciación tumoral, invasión vascular y grado de regresión tumoral (tumour regression grade, TRG) de Mandard. Los grados TRG 1 y 2 fueron considerados como una buena respuesta y el resultado primario fue la supervivencia global (overall survival, OS). RESULTADOS: Durante el seguimiento de 136 pacientes, 36 pacientes (26,5%) presentaron recidiva y 69 pacientes (50,7%) fallecieron. El análisis de las características operativas del receptor (receiver-operator-characteristic, ROC) de NLR antes de la NAC predijo una pobre TRG (área bajo la curva ROC, AUC 0,71, i.c. del 95% 0,58-0,83, P = 0,002). En el análisis univariable, el estadio pT (P < 0,001), el estadio pN (P < 0,001), una pobre diferenciación tumoral (P = 0,006), un margen positivo (P = 0,001), una pobre TRG (P = 0,014) y la NLR (dicotomizada a 2,25, P = 0,017) se asociaron con una pobre OS, pero solamente la NLR (cociente de riesgos instantáneos, hazard ratio, HR 2,28, i.c. del 95% 1,03-4,93, P = 0,042) conservó la significación estadística como variable independiente en el análisis multivariable. CONCLUSIÓN: La NLR antes del tratamiento se asoció con respuesta patológica del OAC a la NAC y OS.

Value of individual surgeon performance metrics as quality assurance measures in oesophagogastric cancer surgery.

BACKGROUND: Surgeon-level operative mortality is widely seen as a measure of quality after gastric and oesophageal resection. This study aimed to evaluate this alongside a compound-level outcome analysis. METHODS: Consecutive patients who underwent treatment including surgery delivered by a multidisciplinary team, which included seven specialist surgeons, were studied. The primary outcome was death within 30 days of surgery; secondary outcomes were anastomotic leak, Clavien-Dindo morbidity score, lymph node harvest, circumferential resection margin (CRM) status, disease-free (DFS), and overall (OS) survival. RESULTS: The median number of annual resections per surgeon was 10 (range 5-25), compared with 14 (5-25) for joint consultant teams (P = 0·855). The median annual surgeon-level mortality rate was 0 (0-9) per cent versus an overall network annual operative mortality rate of 1·8 (0-3·7) per cent. Joint consultant team procedures were associated with fewer operative deaths (0·5 per cent versus 3·4 per cent at surgeon level; P = 0·027). The median surgeon anastomotic leak rate was 12·4 (range 9-20) per cent (P = 0·625 versus the whole surgical range), overall morbidity 46·5 (31-60) per cent (P = 0·066), lymph node harvest 16 (9-29) (P < 0·001), CRM positivity 32·0 (16-46) per cent (P = 0·003), 5-year DFS rate 44·8 (29-60) per cent and OS rate 46·5 (35-53) per cent. No designated metrics were independently associated with DFS or OS in multivariable analysis. CONCLUSION: Annual surgeon-level metrics demonstrated wide variations (fivefold), but these performance metrics were not associated with survival.

ANTECEDENTES: La mortalidad operatoria relacionada con el nivel del cirujano se contempla ampliamente como una medida de calidad tras la resección esofágica. Este estudio tenía como objetivo evaluar este aspecto junto con un análisis de resultados conjuntos a nivel de procedimientos. MÉTODOS: Se estudiaron los pacientes consecutivos que fueron tratados, incluyendo el tratamiento quirúrgico, efectuado por un equipo multidisciplinar formado por siete cirujanos especialistas. La variable principal de resultados era la mortalidad a durante los primeros 30 días de la cirugía, y las variables secundarias fueron la fuga anastomótica, la gravedad de la puntuación de morbilidad de Clavien-Dindo, el número de ganglios linfáticos obtenidos, el estado del margen circunferencial (circumferential margin, CRM), la supervivencia libre de enfermedad (disease-free survival, DFS) y la supervivencia global (overall survival, OS). RESULTADOS: La mediana del número anual de resecciones por cirujano fue de 10 (rango 5-25, P = 0,855). El nivel de la mediana de mortalidad anual por cirujano fue del 0% (0-9,1) y la mortalidad operatoria anual global del equipo de 1,8% (0-3,7, P = 0,389). Los procedimientos conjuntos del equipo consultor se asociaron con menos muertes operatorias (0,5 versus 3,4%, P = 0,027). La tasa mediana (rango) de fuga anastomótica por cirujano fue del 12% (9-20, P = 0,625), la morbilidad global del 46,7% (31-60, P = 0,003), la DFS a los 5 años del 44,8% (28,6-60,0, P = 0,257) y la OS del 46,5% (35,0-52,5, P = 0,573). Ningún factor mostró una asociación independiente con la DFS o la OS en el análisis multivariable. CONCLUSIÓN: Las medidas anuales a nivel de cirujano demostraron amplias variaciones (9 veces), pero estas medidas de rendimiento no se asociaron con la supervivencia.

A novel tumor-based epithelial-to-mesenchymal transition score that associates with prognosis and metastasis in patients with Stage II/III colorectal cancer.

It is increasingly appreciated that host factors within the tumor center and microenvironment play a key role in dictating colorectal cancer (CRC) outcomes. As a result, the metastatic process has now been defined as a result of epithelial-mesenchymal transition (EMT). Establishment of the role of EMT within the tumor center and its effect on the tumor microenvironment would be beneficial for prognosis and therapeutic intervention in CRC. The present study assessed five immunohistochemical EMT markers within the tumor center on a 185 Stage II/III CRC patient tissue microarray. In 185 patients with CRC, cytoplasmic snail (HR 1.94 95% confidence interval [CI] 1.15-3.29, p = 0.012) and a novel combined EMT score (HR 3.86 95% CI 2.17-6.86, p < 0.001) were associated with decreased cancer-specific survival. The combined EMT score was also associated with increased tumor budding (p = 0.046), and systemic inflammation (p = 0.007), as well as decreased memory T-cells within the stroma (p = 0.030) and at the invasive margin (p = 0.035). Furthermore, the combined EMT score was associated with cancer-specific survival independent of TNM-stage (HR 4.12 95% CI 2.30-7.39, p < 0.001). In conclusion, a novel combined EMT score stratifies patient's survival in Stage II/III CRC and associates with key factors of tumor metastasis. Therefore, the combined EMT score could be used to identify patients at risk of micrometastases and who may benefit from standard adjuvant therapy, potentially in combination with EMT blockade.

Propensity score analysis of 18-FDG PET/CT-enhanced staging in patients undergoing surgery for esophageal cancer.

PURPOSE: PET/CT is now integral to the staging pathway for potentially curable esophageal cancer (EC), primarily to identify distant metastases undetected by computed tomography. The aim of this study was to analyze the effect of PET/CT introduction on survival and assess patterns of recurrence after esophagectomy. METHODS: A longitudinal cohort of EC patients staged between 1998 and 2016 were considered for inclusion. After co-variate adjustment using propensity scoring, a cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent esophagectomy [median age 63 years (31-80), 395 males, 425 adenocarcinomas, 71 squamous cell carcinomas, 325 neoadjuvant therapy] were included. The primary outcome measure was overall survival (OS) based on intention to treat. RESULTS: Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (Chi2 6.571, df 1, p = 0.004). On multivariable analysis, pT stage (HR 1.496 [95% CI 1.28-1.75], p < 0.0001), pN stage (HR 1.114 [95% CI 1.04-1.19], p = 0.001) and PET/CT staging (HR 0.688 [95% CI 0.53-0.89] p = 0.004) were independently associated with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT, compared with 74 patients post-PET/CT (37.8%, p = 0.004), and was less likely to be distant recurrence after PET/CT introduction (39.5 vs. 27.0%, p = 0.006). CONCLUSIONS: Enhanced PET/CT staging is an important modality and independent factor associated with improved survival in patients undergoing esophagectomy for cancer.

Meta-analysis of the prognostic value of CpG island methylator phenotype in gastric cancer.

BACKGROUND: CpG island methylator phenotype (CIMP) has been identified as a distinct molecular subtype of gastric cancer, yet associations with survival are conflicting. A meta-analysis was performed to estimate the prognostic significance of CIMP. METHODS: Embase, MEDLINE, PubMed, PubMed Central and Cochrane databases were searched systematically for studies related to the association between CIMP and survival in patients undergoing potentially curative resection for gastric cancer. RESULTS: A total of 918 patients from ten studies were included, and the median proportion of tumours with CIMP-high (CIMP-H) status was 40·9 (range 4·8-63) per cent. Gene panels for assessing CIMP status varied between the studies. Pooled analysis suggested that specimens exhibiting CIMP-H were associated with poorer 5-year survival (odds ratio (OR) for death 1·48, 95 per cent c.i. 1·10 to 1·99; P = 0·009). Significant heterogeneity was observed between studies (I2 = 88 per cent, P < 0·001). Subgroup analysis according to whether studies showed a tendency towards poor (5 studies) or improved (5) outcomes for patients with CIMP-H tumours, revealed that CIMP-H was associated with both poor (OR for death 8·15, 4·65 to 14·28, P < 0·001; heterogeneity I2 = 52 per cent, P = 0·08) and improved (OR 0·42, 0·27 to 0·65; P < 0·001, heterogeneity I2 = 0 per cent, P = 0·960) survival. CONCLUSION: There was heterogeneity in the gene panels used to identify CIMP, which may explain the survival differences.

Esophageal cancer's 100 most influential manuscripts: a bibliometric analysis.

Bibliometric analysis highlights key topics and publications that have shaped the understanding and management of esophageal cancer (EC). Here, the 100 most cited manuscripts in the field of EC are analyzed. The Thomson Reuters Web of Science database with the search terms 'esophageal cancer' or 'esophageal carcinoma' or 'oesophageal cancer' or 'oesophageal carcinoma' or 'gastroscopy' was used to identify all English language full manuscripts for the study. The 100 most cited papers were further analyzed by topic, journal, author, year, and institution. A total of 121,556 eligible papers were returned and the median (range) citation number was 406.5 (1833 to 293). The most cited paper focused on the role of perioperative chemotherpy in EC (1833 citations). Gastroenterology published the highest number of papers (n = 15, 6362 citations) and The New England Journal of Medicine received the most citations (n = 12, 12125 citations). The country and year with the greatest number of publications were the USA (n = 50), and 1998, 1999, and 2000 (n = 7). The most ubiquitous topic was the pathology of EC (n = 66) followed by management of EC (n = 54), and studies related to EC prognosis (n = 44). The most cited manuscripts highlighted the pathology, management, and prognosis of EC and this bibliometirc review provides the most influential references serving as a guide to popular research themes.

The in situ local immune response, tumour senescence and proliferation in colorectal cancer.

BACKGROUND: Immune cell infiltrates are important determinants of colorectal cancer (CRC) outcome. Their presence may be driven by tumour or host-specific factors. From previous studies in mice, senescence, a state of cell cycle arrest, may moderate tumour progression through upregulation of antitumour immune responses. The relationships between senescence and immune infiltrates have not previously been studied in humans. We explore whether a marker of senescence (p16(ink4a)) in combination with low level expression of a proliferation marker (ki-67) relate to T cell infiltrates in CRC, and whether p16(ink4a), Ki-67 and immune infiltrates have similar prognostic value. METHODS: Immunostaining of p16(inka) and Ki-67 was performed within a CRC tissue microarray. Nuclear p16(inka) and Ki-67 were categorised as high/low. T-cell markers, CD3, CD45RO, CD8 and FOXP3 were scored separately as high/low grade in three areas of the tumour: the invasive margin (IM), tumour stroma and cancer cell nests (CCNs). results: Two hundred and thirty stage I-III cancers were studied. High nuclear p16(ink4a) was expressed in 63% and high proliferation (Ki-67 >15%) in 61%. p16(ink4a) expression was associated with reduced CD45RO+ cells at the IM (P<0.05) and within the stroma (P<0.05) and reduced CD8+ cells at the IM (P<0.01). A low Ki-67 proliferative index was associated with reduced density of CD3+ cells in CCNs (P<0.01), reduced CD45RO+ cells at the IM (P<0.05) and within the CCNs (P<0.001), reduced FOXP3+ cells at the IM (P<0.001), within the stroma (P=0.001) and within CCNs (P<0.001) and reduced CD8+ cells at the IM (P<0.05) and within the CCNs (P<0.05). Tumours with both a low proliferative index and expression of p16(ink4a) demonstrated similar consistent relationships with reduced densities of T-cell infiltrates. On multivariate analysis, TNM stage (P<0.001), low CD3 cells at the IM (P=0.014), low CD8 cells at the IM (P=0.037), low proliferation (Ki-67; P=0.013) and low senescence (p16(ink4a); P=0.002) were independently associated with poorer cancer survival. CONCLUSION: Senescence, proliferation and immune cell infiltrates are independent prognostic factors in CRC. Although related to survival, p16(ink4a)-associated senescence is not associated with an upregulation of antitumour T-cell responses.

The relationship between tumour site, clinicopathological characteristics and cancer-specific survival in patients undergoing surgery for colorectal cancer.

AIM: It is recognised that colorectal cancer may arise from different genomic instability pathways. There is evidence to suggest that colon and rectal cancers exhibit different clinicopathological features. We examined the relationship between tumour site, clinicopathological characteristics and cancer-specific survival in patients undergoing potentially curative resection for colorectal cancer. METHOD: Four hundred and eleven patients who underwent surgery. Clinicopathological data including components of the Peterson index, Klintrup scores, haemoglobin and the modified Glasgow Prognostic Score (mGPS) were studied. RESULTS: There were 134 (33%) right sided, 125 (30%) left sided and 152 (37%) rectal tumours. Emergency presentation (P < 0.001), anaemia (P < 0.001), higher mGPS (P < 0.001), advanced T stage (P < 0.001), poor differentiation (P < 0.001) and older age (P < 0.05) were more commonly observed in right sided cancer. The mean follow-up was 94 months (minimum 36 months) and 114 patients died of cancer. There was no difference between tumour site and survival (P = 0.427). On multivariate analysis older age (P = 0.015), lymph node ratio (P < 0.001), mGPS (P = 0.028), Peterson Index (P < 0.001) and Klintrup score (P = 0.008) were independently related to cancer-specific survival. Klintrup score was only associated with poor cancer-specific survival in rectal cancer (P = 0.009). CONCLUSION: The study suggests that colorectal cancer is a group of heterogeneous tumours with different clinicopathological features. Despite this, there was no difference between tumour site and survival. The prognostic role of clinicopathological factors in tumours arising from different genomic instability pathways requires further study.

New drug targets for the treatment of obesity.

There is a huge void in the current pharmacological treatment options for obesity. This gap is surprising given the high prevalence and associated costs of obesity. Many factors have prevented active drug development, including the poor safety and efficacy of earlier antiobesity drugs. However, there are now several compelling targets on the horizon. The new generation of antiobesity drugs offers hope for the management of obesity, but no single agent is likely to be a panacea. Rather, obesity will need to be managed like many other chronic diseases, with combination therapies and long-term treatment in order to achieve sustained success. New targets have arisen as more research has been performed to understand the complex circuitry that controls energy homeostasis. The goal of this review is to discuss the latest pharmacological agents and strategies that are under development and that may eventually be used for the treatment of obesity.