Cost-Outcome of Radiotherapy for Local Control and Overall Survival Benefits in Breast Cancer.

PURPOSE: Radiotherapy (RT) is an integral component in the treatment of breast cancer. The aims of this study were to estimate the cost per 5-year Local Control (LC) and Overall Survival (OS) benefits of the first course of RT, based on breast cancer stage, and the potential cost savings with adoption of the FAST-Forward protocol. METHODS AND MATERIALS: All RT activities for breast cancer RT July 2017-June 2020 and their associated costs were consolidated together. The average cost of treatment course was calculated (average cost per fraction X average no. of fractions). Cost per outcome was estimated based on published gains in 5-year LC and OS with optimal use of radiotherapy. RESULTS: 481 patients with breast cancer were analysed. The average cost per fraction was $285 AUD (£148 GBP) for all stages. The average costs for 5-year LC and OS gain were $31,483 AUD (£16 392 GBP) and $235,435 AUD (£122 566 GBP) respectively for all stages. The estimated costs for 5-year LC outcomes were $29,675 AUD (£15 450 GBP), $34,675 AUD (£18 053 GBP) and $32,478 AUD (£16 910 GBP) for Stage I-III respectively. The estimated costs for 5-year OS were $455,909 AUD (£237 378 GBP), $532,727 AUD (£ 277 375 GBP) and $60,717 AUD (£31 614 GBP) for Stage I-III respectively. 266 patients had characteristics that made them eligible for the FAST-Forward protocol. A cost saving of $2592-3864 AUD (£1350-2012 GBP) per patient was estimated had these patients been treated with the protocol. CONCLUSIONS: The cost of RT for LC outcome is similar across stages. The greatest value for OS outcome was seen in patients with Stage III breast cancer, due to the greater survival benefit with RT in these patients compared with Stage I-II breast cancer. Significant cost savings can be made by implementing the FAST-Forward protocol.

Microwave demonstration of Purcell effect enhanced radiation efficiency.

We experimentally demonstrate a Purcell effect-based design technique for improved impedance matching, and thus enhanced the reflection coefficient from a small microwave emitter. Using an iterative process centred on comparing the phase of the radiated field of the emitter in air with that of the emitter in a dielectric environment, we optimise the structure of a dielectric hemisphere above a ground plane surrounding a small monopolar microwave emitter in order to maximise its radiation efficiency. The optimised system shows very strong coupling between the emitter and two omnidirectional radiation modes at 1.99 GHz and 2.84 GHz, yielding Purcell enhancement factors of 1762 and 411 times increase respectively, and near perfect radiation efficiency.

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.

Functional mutants of Azospirillum brasilense elicit beneficial physiological and metabolic responses in Zea mays contributing to increased host iron assimilation.

Iron (Fe), an essential element for plant growth, is abundant in soil but with low bioavailability. Thus, plants developed specialized mechanisms to sequester the element. Beneficial microbes have recently become a favored method to promote plant growth through increased uptake of essential micronutrients, like Fe, yet little is known of their mechanisms of action. Functional mutants of the epiphytic bacterium Azospirillum brasilense, a prolific grass-root colonizer, were used to examine mechanisms for promoting iron uptake in Zea mays. Mutants included HM053, FP10, and ipdC, which have varying capacities for biological nitrogen fixation and production of the plant hormone auxin. Using radioactive iron-59 tracing and inductively coupled plasma mass spectrometry, we documented significant differences in host uptake of Fe2+/3+ correlating with mutant biological function. Radioactive carbon-11, administered to plants as 11CO2, provided insights into shifts in host usage of 'new' carbon resources in the presence of these beneficial microbes. Of the mutants examined, HM053 exhibited the greatest influence on host Fe uptake with increased plant allocation of 11C-resources to roots where they were transformed and exuded as 11C-acidic substrates to aid in Fe-chelation, and increased C-11 partitioning into citric acid, nicotianamine and histidine to aid in the in situ translocation of Fe once assimilated.

Complaints of neuropathic pain, noxious cervical plexus neuropathy and neck tightness are reported by patients who undergo neck dissection: an institutional study and narrative review.

There exists a subgroup of patients who undergo neck dissection (ND) who postoperatively complain of either neuropathic pain, dysaesthesia and/or discomfort that is located within the dermatomal distribution of the cervical plexus. The purpose of our study was to determine the prevalence, characteristic, and demographics of these symptoms in our patient cohort. We undertook a retrospective randomised observational cohort study of 105 patients who had undergone ND. The primary predictor variable was the undertaking of a ND. The secondary outcome variable was the complaint of either neuropathic pain or a noxious neuropathy, at a minimum of twelve months after surgery. A recognised symptom questionnaire and a visual analogue score was employed for the purpose of the study. A descriptive and statistical analysis was applied to the assembled data. Twenty patients (19%) complained of either spontaneous (n=9) or evoked (n=11) neuropathic pain that occurred within the surgical site. In addition, 71 patients (68%) described an altered sensation in the dermatomal distribution of the great auricular or tranverse cervical nerves while 70 patients (67%) described the feeling of 'neck tightness'. There were no characteristics of the study cohort that underpinned these results. Neuropathic pain can occur following ND. This can cause distress to a small but defined group of patients. Despite its importance, we found a paucity of studies in the literature that have investigated neuropathic pain following ND. We believe this condition requires more research attention and clinical awareness.

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.

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.

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.

Tension band wiring versus locking plate fixation for simple, two-part Mayo 2A olecranon fractures: a comparison of post-operative outcomes, complications, reoperations and economics.

PURPOSE: Simple displaced transverse olecranon fractures are traditionally managed operatively with a tension band wire device (TBW). We compared clinical outcomes, morbidity and the cost of treatment of TBW versus pre-countered low-profile locking plates for the treatment of Mayo 2A fractures. PATIENT AND METHODS: All olecranon fractures admitted to our unit between 2008 and 2014 were identified (n = 129). Patient notes and radiographs were studied from presentation to final follow-up. Patient outcomes were recorded using the QuickDASH (Disabilities of Arm, Shoulder and Hand) score. Patient demographics and nature of complications were recorded as were the rate and nature of any repeat operation. RESULTS: Eighty-nine patients had Mayo 2A fractures (69%). Sixty-four underwent TBW (n = 48) or locking plate fixation (n = 16). The mean ages of both groups were similar at 57 (15-93) and 60 (22-80), respectively. In the TBW group, the mean post-injury QuickDASH was 12.9, compared with 15.0 for the locking plate group. There was no statistically significant difference between the outcomes for either group. Nineteen of the 48 TBW patients had complications (39.6%). Sixteen of the 48 TBW patients had reoperations (33.3%). In particular, we would highlight that 13 (27.1%) of patients treated with TBW underwent subsequent removal of metalwork for hardware irritation. There were no complications and or reoperations in the 16 patients who received locking plate fixation. Both complication and reoperation rates were statistically significantly different. Despite being initially more expensive, when the cost of reoperation for TBW group was included, locking plates were found to be on average £236.33 less per patient than for TBW. CONCLUSIONS: We suggest that locking plates are superior to TBW concerning post-operative morbidity, reoperation rate and cost for Mayo 2A fractures in contrast to previous articles. LEVEL OF EVIDENCE: Therapeutic study, III.

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.

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.

Long-term systolic function in children and young adults after hematopoietic stem cell transplant.

Congestive heart failure and subclinical left ventricular systolic dysfunction (LVSD) affect long-term survivors of hematopoietic stem cell transplant (HSCT). Echocardiographic measurements of global longitudinal and circumferential strain have shown promise in identifying subclinical LVSD in cancer survivors. We analyzed echocardiograms in 95 children and young adults with malignancies or bone marrow failure syndromes performed before HSCT and 1-6 years after HSCT. We additionally measured the biomarkers soluble suppression of tumorigenicity-2 (sST-2) and cardiac troponin-I (cTn-I) in the same children through 49 days post HSCT. Ejection fraction (EF) after HSCT was unchanged from baseline (baseline: z-score -0.73 vs long-term follow up: -0.44, P=0.11). Global longitudinal strain was unchanged from baseline (-20.66 vs -20.74%, P=0.90) as was global circumferential strain (-24.3 vs -23.5%, P=0.32). Levels of sST-2 were elevated at all time points compared with baseline samples and cTn-I was elevated at days 14 and 28. Cardiac biomarkers at any time point did not correlate with long-term follow-up EF. In children and young adult survivors of HSCT, EF was unchanged in the first years after HSCT. Elevation in cardiac biomarkers occurring after HSCT suggest subclinical cardiac injury occurs in many patients and long-term monitoring for LVSD should continue.

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 treatment of olecranon fractures in adults.

Olecranon fractures are common. They are usually managed surgically with open reduction and either tension band wiring or plate fixation. Currently, there are few studies comparing fracture treatments. We aim to review the available literature to guide the orthopaedic surgeon on the management of these fractures. A literature review of peer-reviewed publications in international orthopaedic journals detailing olecranon fracture treatment was conducted. An additional focus was placed on the evidence base for and surgical outcomes of tension band wiring for common two-part fractures. Our novel illustrations aim to educate the reader, and our treatment algorithm provides guidance for management. 10% of all upper limb fractures involve the olecranon, and most are simple two-part injuries. These should be managed with tension band wire constructs. Non-displaced fractures can be treated conservatively. Displaced complex injuries necessitate locking plate fixation. Currently, there exits a lack of studies comparing these treatments. There may be an emerging role for intramedullary nail fixation. Non-operative management in the elderly comorbid patient remains controversial. Prospective, randomised controlled trials of matched patients and fracture patterns comparing operative techniques are needed as there is a lack of level I/II evidence to support the use of one implant over another.

Managing complex respiratory patients in the community: an evaluation of a pilot integrated respiratory care service.

INTRODUCTION: In the UK, there is significant variation in respiratory care and outcomes. An integrated approach to the management of high-risk respiratory patients, incorporating specialist and primary care teams' expertise, is the basis for new integrated respiratory services designed to reduce this variation; however, this model needs evaluating. METHODS: To evaluate an integrated service managing high-risk respiratory patients, electronic searches for patients with asthma and chronic obstructive pulmonary disease at risk of poor outcomes were performed in two general practitioner (GP) practices in a local service-development initiative. Patients were reviewed at joint clinics by primary and secondary care professionals. GPs also nominated patients for inclusion. Reviews were delivered to best standards of care including assessments of diagnosis, control, spirometry, self-management, education, medication, inhaler technique and smoking cessation support. Follow-up of routine clinical data collected at 9-months postclinic were compared with seasonally matched 9-months prior to integrated review. RESULTS: 82 patients were identified, 55 attended. 13 (23.6%) had their primary diagnosis changed. In comparison with the seasonally adjusted baseline period, in the 9-month follow-up there was an increase in inhaled corticosteroid prescriptions of 23.3%, a reduction in short-acting ß2-agonist prescription of 33.3%, a reduction in acute respiratory exacerbations of 67.6%, in unscheduled GP surgery visits of 53.3% and acute respiratory hospital admissions reduced from 3 to 0. Only 4 patients (7.3%) required referral to secondary care. Health economic evaluation showed respiratory-related costs per patient reduced by £231.86. CONCLUSIONS: Patients with respiratory disease in this region at risk of suboptimal outcomes identified proactively and managed by an integrated team improved outcomes without the need for hospital referral.

Tet-mediated imprinting erasure in H19 locus following reprogramming of spermatogonial stem cells to induced pluripotent stem cells.

Selective methylation of CpG islands at imprinting control regions (ICR) determines the monoparental expression of a subset of genes. Currently, it is unclear whether artificial reprogramming induced by the expression of Yamanaka factors disrupts these marks and whether cell type of origin affects the dynamics of reprogramming. In this study, spermatogonial stem cells (SSC) that harbor paternalized imprinting marks, and fibroblasts were reprogrammed to iPSC (SSCiPSC and fiPSC). The SSCiPSC were able to form teratomas and generated chimeras with a higher skin chimerism than those derived from fiPSC. RNA-seq revealed extensive reprogramming at the transcriptional level with 8124 genes differentially expressed between SSC and SSCiPSC and only 490 between SSCiPSC and fiPSC. Likewise, reprogramming of SSC affected 26 of 41 imprinting gene clusters known in the mouse genome. A closer look at H19 ICR revealed complete erasure in SSCiPSC in contrast to fiPSC. Imprinting erasure in SSCiPSC was maintained even after in vivo differentiation into teratomas. Reprogramming of SSC from Tet1 and Tet2 double knockout mice however lacked demethylation of H19 ICR. These results suggest that imprinting erasure during reprogramming depends on the epigenetic landscape of the precursor cell and is mediated by TETs at the H19 locus.