Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin.

BACKGROUND: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins. METHODS: Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence-free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score-matched analysis was also performed. RESULTS: Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence-free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non-responders (Mandard tumour regression grade 4-5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score-matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence-free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment. CONCLUSION: Adjuvant therapy may improve overall survival and recurrence-free survival after margin-positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non-responders to neoadjuvant chemotherapy.

ANTECEDENTES: El papel del tratamiento adyuvante en pacientes con adenocarcinoma esofagogástrico tratados con quimioterapia neoadyuvante es polémico. En la práctica del Reino Unido, el estado del margen de resección quirúrgico se utiliza a menudo para identificar a los pacientes que reciben tratamiento adyuvante. El objetivo de este estudio fue evaluar el beneficio en la supervivencia del tratamiento adyuvante en pacientes con márgenes de resección positivos (R1). MÉTODOS: Se combinaron dos bases de datos de instituciones del Reino Unido que recogen información de forma prospectiva para identificar pacientes elegibles. Se utilizaron análisis de regresión de Cox ajustados para comparar la supervivencia global y la supervivencia libre de recidiva según el tratamiento adyuvante. Los patrones de recidiva se evaluaron como resultado secundario. También se realizó un análisis de emparejamiento por puntaje de propensión. RESULTADOS: De 616 pacientes incluidos en la base de datos combinada, se incluyeron en el estudio 242 pacientes con resección R1. De estos pacientes, 112 (46%) recibieron quimiorradioterapia adyuvante, 46 (19%) pacientes fueron tratados con quimioterapia adyuvante y 84 (35%) pacientes no recibieron ningún tratamiento. En el análisis ajustado, la quimiorradioterapia adyuvante mejoró la supervivencia libre de recidiva (cociente de riesgos instantáneos, hazard ratio, HR 0,59, i.c. del 95% 0,38-0,94; P = 0,026) con un beneficio tanto para la recidiva local (HR 0,48, i.c. del 95% 0,24-0,99; P = 0,047) como para la sistémica (HR 0,56, i.c. del 95% 0,33-0,94; P = 0,027). Cuando los pacientes se clasificaron según la respuesta tumoral a la quimioterapia neoadyuvante, los no respondedores (Mandard Grado 4/5) tratados con quimiorradioterapia adyuvante obtuvieron un beneficio en la supervivencia (HR 0,61, i.c. del 95% 0,38-0,97; P = 0,037). En el análisis por emparejamiento por puntaje de propensión, se observó un beneficio en la supervivencia global (HR 0,62, i.c. del 95% 0,39-0,98; P = 0,042) y en la supervivencia libre de recidiva (HR 0,51.i.c. del 95% 0,30-0,87; P = 0,004) con la quimiorradioterapia adyuvante frente a no recibir tratamiento adyuvante. CONCLUSIÓN: El tratamiento adyuvante puede mejorar la supervivencia global y la supervivencia libre de recidiva en pacientes con margen de resección positivo. Este patrón parece más pronunciado con la quimiorradioterapia adyuvante en pacientes que no responden a la quimioterapia.

Laparoscopic-assisted left thoracoabdominal esophagectomy (LLTA): an innovative approach for locally advanced tumors of the gastroesophageal junction.

PURPOSE: To report a novel approach for locally advanced tumors located at the gastroesophageal junction (GEJ) using a laparoscopic abdominal phase and open left thoracotomy with the patient in a single right lateral decubitus position. BACKGROUND: The standard open left thoracoabdominal approach offers excellent exposure and access to the GEJ and lower esophagus. It also involves a single position for the procedure, shortening the operation time. The disadvantages are a large incision, division of the costochondral junction, and a low-level thoracotomy. The laparoscopic-assisted left thoracoabdominal esophagectomy (LLTA) is performed with the patient in the same right lateral decubitus position, but initially rolled away from the operator at 45° allowing laparoscopic gastric mobilization and lymphadenectomy. The patient is then tilted back to the lateral position for the thoracic phase. An anterolateral left thoracotomy is performed through the higher fifth intercostal space allowing a high intrathoracic anastomosis, just below the aortic arch. No disruption of the costochondral junction is made. METHODS: Consecutive patients selectively treated for locally advanced GEJ tumors with an LLTA approach between 2013 and 2019 were analyzed and compared to national standards (NOGCA). RESULTS: This series of 74 consecutive patients had a mean age of 63 years. The median operation time was 235 minutes. The median inpatient stay was 10 days (NOGCA 9 [11-17]). The tumors were predominantly adenocarcinoma (95%) and located at the GEJ (92%). The majority were locally advanced T3 or T4 tumors. Postoperative morbidity was low, Clavien-Dindo (C-D) 0 in 52.7% patients, C-D1 (1.4%), C-D2 (31.1%), C-D3a (5.4%), C-D4a (9.5%), and C-D5 (1.4%). The median number of total lymph nodes (LN) excised was 28 (NOGCA >15); LN % yield ≥18 was 90% (NOGCA 82.5%). Positive nodes were located at the lesser-curve (40%), paraesophageal (32.4%), and subcarinal regions (2.7%). Positive circumferential resection margins (<1 mm) were present in 28.4% of resected specimens (NOGCA 25.1%). This is reflective of the high proportion T3/T4 tumors selected for this approach. Hospital and 30-day mortality was 1.4% (NOGCA 2.7%). Recurrence after LLTA was 25.7% (local 5.4%, systemic 17.6%, mixed 2.7%) at a median of 311 days (62-1,158). CONCLUSION: This series demonstrates a novel, safe, and reproducible approach for locally advanced cancer of the GEJ. It offers a better exposure of the hiatus than the right-sided approach and avoids division of the costochondral junction and low thoracotomy seen with the open left thoracoabdominal approach.

Guy's cancer cohort - real world evidence for cancer pathways.

BACKGROUND: The burden of disease due to cancer remains substantial. Since the value of real-world evidence has also been recognised by regulatory agencies, we established a Research Ethics Committee (REC) approved research database for cancer patients (Reference: 18/NW/0297). CONSTRUCTION AND CONTENT: Guy's Cancer Cohort introduces the concept of opt-out consent processes for research in a subset of oncology patients diagnosed and treated at a large NHS Trust in the UK. From April 2016 until March 2017, 1388 eligible patients visited Guy's and St Thomas' NHS Foundation Trust (GSTT) for breast cancer management. For urological cancers this number was 1757 and for lung cancer 677. The Cohort consists of a large repository of routinely collected clinical data recorded both retrospectively and prospectively. The database contains detailed clinical information collected at various timepoints across the treatment pathway inclusive of diagnostic data, and data on disease progression, recurrence and survival. CONCLUSIONS: Guy's Cancer Cohort provides a valuable infrastructure to answer a wide variety of research questions of a clinical, mechanistic, and supportive care nature. Clinical research using this database will result in improved patient safety and experience. Guy's Cancer Cohort promotes collaborative research and will accept applications for the release of anonymised datasets for research purposes.

Clinical significance of pulmonary nodules in decision-making and management of patients diagnosed with esophageal cancer.

In esophageal cancer, metastatic spread to the lungs is detected in 4-9.7% of cases. During staging investigations, 22% of patients have pulmonary nodules detected on cross-sectional imaging. The purpose of this study is to elucidate the clinical importance of these incidentally found pulmonary nodules, in patients with clinically localized esophageal cancer. A retrospective cohort study was conducted from January 2008 to December 2012 in a tertiary esophagogastric referral center. One-hundred and forty-nine patients were included in the study. All patients underwent dedicated staging followed by neoadjuvant chemotherapy and surgery as indicated. Thirty-three (22.1%) patients had pulmonary nodules found in their preoperative staging. Only three (9%) patients proved to develop metastatic pulmonary disease on follow-up. Interestingly, in all three patients, the nodules were negative on initial 18-fluorodeoxyglucose positron emission tomography. Incidentally found pulmonary nodules in newly diagnosed patients with esophageal cancer during staging investigations are rarely metastases. Such nodules, in isolation, should not preclude patients from radical treatment.

Prediction of a positive circumferential resection margin at surgery following neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.

Background: A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods: Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results: A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3-4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT-assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c-index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4-5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion: The presence of advanced cT status, poor tumour differentiation, and CT-assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.

Antecedentes: Un margen de resección circunferencial (circumferential resection margin, CRM) positivo se ha asociado con tasas más elevadas de recidiva locorregional y peor supervivencia en el cáncer de esófago. El objetivo de este estudio fue establecer si las variables clínico­patológicas y radiológicas podrían predecir la positividad del CRM en el adenocarcinoma de esófago tras quimioterapia neoadyuvante antes de la cirugía. Métodos: Se realizó un análisis multivariable de las características clínico­patológicas y de la tomografía computarizada (computed tomography, CT) que se consideraron potencialmente predictivas de CRM en la estadificación inicial y tras la quimioterapia neoadyuvante. Se construyeron modelos de predicción. Se evaluó el área bajo la curva (area under curve, AUC) con el i.c. del 95% a partir de 1.000 muestras bootstrap. Resultados: Se incluyeron 223 pacientes en el estudio. Una pobre diferenciación (razón de oportunidades, odds ratio, OR 2,84, i.c. del 95% 1,39­6,01) y un estadio clínico T avanzado (T3­4) (OR 2,93, i.c. del 95% 1,03­9,48) se asociaron de forma independiente con un riesgo aumentado de CRM en el diagnóstico. La falta de respuesta en la CT (estable o enfermedad en progresión) tras la quimioterapia se correspondía de forma independiente con un riesgo aumentado de CRM positivo (OR 3,38, i.c. del 95% 1,43­8,50). Además, la evidencia por CT de invasión local y un mayor volumen del tumor en CT (14 cm3) mejoraron el funcionamiento del modelo predictivo, incluyendo todos los parámetros previamente señalados; con AUC (índice c) de 0,76 (0,68­0,83). Las variables asociadas de forma significativa con tasas más elevadas de recidiva locorregional fueron el estado de los ganglios linfáticos patológicos (P = 0,002), la invasión linfovascular (P = 0,007) y la respuesta pobre a la quimioterapia (Mandard 4 y 5 (P = 0,006)). La positividad del CRM se asoció con una tasa de recidiva locorregional más elevada pero sin alcanzar significación estadística (P = 0,09). Conclusión: La presencia de un estadio clínico T avanzado, tumor pobremente diferenciado, falta de respuesta a la quimioterapia en la TC, mayor volumen del tumor en la TC e invasión local pueden ser utilizados para identificar pacientes en riesgo de un CRM positivo tras quimioterapia neoadyuvante.

A seven-Gene Signature assay improves prognostic risk stratification of perioperative chemotherapy treated gastroesophageal cancer patients from the MAGIC trial.

Background: Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse. Patients and methods: The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort. Results: Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS [hazard ratio (HR) 5.1; P < 0.0001]. The median OS of high- and low-risk groups were 10.2 [95% confidence interval (CI) of 6.5 and 13.2 months] and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings. Conclusions: These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.

Impact of incremental circumferential resection margin distance on overall survival and recurrence in oesophageal adenocarcinoma.

BACKGROUND: Previous analyses of the oesophageal circumferential resection margin (CRM) have focused on the prognostic validity of two different definitions of a positive CRM, that of the College of American Pathologists (tumour at margin) and that of the Royal College of Pathologists (tumour within 1 mm). This study aimed to analyse the validity of these definitions and explore the risk of recurrence and survival with incremental tumour distances from the CRM. METHODS: This cohort study included patients who underwent resection for adenocarcinoma of the oesophagus between 2000 and 2014. Kaplan-Meier and Cox regression analyses were performed to determine the hazard ratio (HR) with 95 per cent confidence intervals for recurrence and mortality in CRM increments: tumour at the cut margin, extending to within 0·1-0·9, 1·0-1·9, 2·0-4·9 mm, and 5·0 mm or more from the margin. RESULTS: A total of 444 patients were included in the study. Kaplan-Meier and unadjusted analyses showed a significant incremental improvement in overall survival (P < 0·001) and recurrence (P for trend < 0·001) rates with increasing distance from the CRM. Tumour distance of 2·0 mm or more remained a significant predictor of survival on multivariable analysis (HR for risk of death 0·66, 95 per cent c.i. 0·44 to 1·00). Multivariable analysis of overall survival demonstrated a significant difference between a positive and negative CRM with the Royal College of Pathologists' definition (HR 1·37, 1·01 to 1·85), but not with the College of American Pathologists' definition (HR 1·22, 0·90 to 1·65). CONCLUSION: This study demonstrated an incremental improvement in survival and recurrence rates with increasing tumour distance from the CRM.

Lymph node regression and survival following neoadjuvant chemotherapy in oesophageal adenocarcinoma.

BACKGROUND: The aim was to define the pathological response in lymph nodes following neoadjuvant chemotherapy for oesophageal adenocarcinoma and to quantify any associated survival benefit. METHODS: Lymph nodes retrieved at oesophagectomy were examined retrospectively by two pathologists for evidence of a response to chemotherapy. Patients were classified as lymph node-negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive (allocated a lymph node regression score based on the proportion of fibrosis to residual tumour). Lymph node responders (score 1, complete response; 2, less than 10 per cent remaining tumour; 3, 10-50 per cent remaining tumour) and non-responders (score 4, more than 50 per cent viable tumour; 5, no response) were compared in survival analyses using Kaplan-Meier and Cox regression analysis. RESULTS: Among 377 patients, 256 had neoadjuvant chemotherapy. Overall, 68 of 256 patients (26·6 per cent) had a lymph node response and 115 (44·9 per cent) did not. The remaining 73 patients (28·5 per cent) had negative lymph nodes with no evidence of regression. Some patients had a lymph node response in the absence of a response in the primary tumour (27 of 99, 27 per cent). Lymph node responders had a significant survival benefit (P < 0·001), even when stratified by patients with or without a response in the primary tumour. On multivariable analysis, lymph node responders had decreased overall (hazard ratio 0·53, 95 per cent c.i. 0·36 to 0·78) and disease-specific (HR 0·42, 0·27 to 0·66) mortality, and experienced reduced local and systemic recurrence. CONCLUSION: Lymph node regression is a strong prognostic factor and may be more important than response in the primary tumour.

Health-related quality of life after open transhiatal and transthoracic oesophagectomy for cancer.

BACKGROUND: Transhiatal and transthoracic oesophagectomy in patients with oesophageal cancer have similar survival rates. Whether these approaches differ in health-related quality of life (HRQoL) is uncertain and was examined in this study. METHODS: Patients undergoing transhiatal or transthoracic surgery for lower-third oesophageal or gastro-oesophageal junctional cancer between 2011 and 2015 were selected from an institutional database. HRQoL outcomes were measured at 6 and 12 months after surgery using validated written questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25). Linear mixed models provided mean score differences (MSDs) with 95 per cent confidence intervals, adjusted for preoperative HRQoL, age, physical status (ASA fitness grade), tumour location, tumour stage, neoadjuvant therapy, adjuvant therapy and postoperative complications. MSD values of 10 or more were regarded as clinically relevant. RESULTS: Some 146 patients underwent transhiatal (86, 58·9 per cent) or transthoracic (60, 41·1 per cent) oesophagectomy. The HRQoL questionnaires were returned by 111 patients at 6 months and 74 at 12 months. At 6 months, transthoracic oesophagectomy was associated with worse role function (MSD -12, 95 per cent c.i. -23 to 0; P = 0·046). At 12 months, patients in the transthoracic group had more nausea and vomiting (MSD 11, 0 to 22; P = 0·045), dyspnoea (MSD 13, 1 to 25; P = 0·029) and constipation (MSD 20, 7 to 33; P = 0·003) than those in the transhiatal group. CONCLUSION: Transhiatal oesophagectomy seems to offer better HRQoL than transthoracic oesophagectomy 6 and 12 months after surgery.

A comparison of the left thoracoabdominal and Ivor-Lewis esophagectomy.

The purpose of this study was to assess the oncological outcomes of a large multicenter series of left thoracoabdominal esophagectomies, and compare these to the more widely utilized Ivor-Lewis esophagectomy. With ethics approval and an established study protocol, anonymized data from five centers were merged into a structured database. The study exposure was operative approach (ILE or LTE). The primary outcome measure was time to death. Secondary outcome measures included time to tumor recurrence, positive surgical resection margins, lymph node yield, postoperative death, and hospital length of stay. Cox proportional hazards models provided hazard ratios (HR) with 95% confidence intervals (CI) adjusting for age, pathological tumor stage, tumor grade, lymphovascular invasion, and neoadjuvant treatment. Among 1228 patients (598 ILE; 630 LTE), most (86%) had adenocarcinoma (AC) and were male (81%). Comparing ILE and LTE for AC patients, no difference was seen in terms of time to death (HR 0.904 95%CI 0.749-1.1090) or time to recurrence (HR 0.973 95%CI 0.768-1.232). The risk of a positive resection margin was also similar (OR 1.022 95%CI 0.731-1.429). Median lymph node yield did not differ between approaches (LTE 21; ILE 21; P = 0.426). In-hospital mortality was 2.4%, significantly lower in the LTE group (LTE 1.3%; ILE 3.6%; P = 0.004). Median hospital stay was 11 days in the LTE group and 14 days in the ILE group (P < 0.0001). In conclusion, this is the largest series of left thoracoabdominal esophagectomies to be submitted for publication and the only one to compare two different transthoracic esophagectomy strategies. It demonstrates oncological equivalence between operative approaches but possible short- term advantages to the left thoracoabdominal esophagectomy.

A national audit of colonic interposition for esophageal replacement.

Esophageal replacement by colonic interposition is an uncommon procedure. This study sought to identify the frequency of this operation in England, identify techniques and associated problems, and also assess health-related quality of life (HR QOL) from the two largest centers performing this procedure. Hospital Episode Statistics were used to identify patients and centers undertaking colon interposition between March 2001 and March 2015. An online survey of UK consultants discussed methods and experience. HR QOL was assessed using the Short Form 36(SF-36v2) with additional gastrointestinal questions. Hospital Episode Statistics identified 328 interpositions (22 in pediatric hospitals). The two highest volume units did 42 and 45 operations, respectively. Thirty-four surgeons (79% response rate) replied to the survey. Fifty-two percent preferred to use the left colon with 81% preferring a substernal placement. The HR QOL survey was performed on 24 patients with a median of 3 years after surgery (ranging from 9 months to 10 years) from the two largest centers and a 56% response rate. Five patients had physical QOL scores above population average and 10 had mental scores above population average. All patients had early satiety, 20 described dysphagia, and 18 regularly took antireflux medication. There was an estimated mean loss of 13.1% body weight (10.6 kg) postoperatively and three patients still relied on a feeding tube for nutrition after an average of 3 years. Colon interposition results in an acceptable long-term QOL. Few centers regularly perform this operation, and centralizing to high-volume centers may lead to better outcomes.

Patterns of recurrence in oesophageal cancer following oesophagectomy in the era of neoadjuvant chemotherapy.

BACKGROUND: Tumour recurrence following oesophagectomy for oesophageal cancer is common despite neoadjuvant treatment. Understanding patterns of recurrence and risk factors associated with locoregional and systemic recurrence might influence future treatment strategies. METHODS: This was a cohort study involving patients undergoing resection for adenocarcinoma or squamous cell carcinoma of the oesophagus between 2000 and 2014. Clinicopathological factors associated with locoregional and systemic recurrence were analysed using multivariable logistic regression to determine odds ratios (ORs) and 95 per cent confidence intervals. RESULTS: Some 698 patients were identified. Lymphovascular invasion (OR 2·09, 95 per cent c.i. 1·18 to 3·71) and preoperative stenting (OR 3·70, 1·34 to 10·23) were independent risk factors for isolated locoregional recurrence. Pathological nodal disease in patients with pT1-2 (pN1: OR 2·72, 1·35 to 5·48; pN2-3: OR 5·00, 2·35 to 10·66) or pT3-4 (pN1: OR 3·03, 1·51 to 6·07; pN2-3: OR 5·75, 3·15 to 10·49) disease predisposed to systemic recurrence. Poor or no response to chemotherapy was also an independent risk factor for isolated systemic recurrence (OR 1·85, 1·05 to 3·26). A positive resection margin (R1 resection) was not associated with a significantly increased risk of isolated locoregional recurrence (OR 1·37, 0·81 to 2·33). CONCLUSION: These findings confirm that oesophageal adenocarcinoma is frequently a systemic disease. Understanding the key predictors of local and systemic recurrence may facilitate the tailoring of oncological therapies to the individual patient.

Prevalence and predictors of anxiety and depression among esophageal cancer patients prior to surgery.

This study aims to establish the prevalence and predictors of anxiety and depression among esophageal cancer patients, post-diagnosis but prior to curatively intended surgery. This was a cross-sectional study using data from a hospital-based prospective cohort study, carried out at St Thomas' Hospital, London. Potential predictor variables were retrieved from medical charts and self-report questionnaires. Anxiety and depression were measured prior to esophageal cancer surgery, using the Hospital Anxiety and Depression Scale. Prevalence of anxiety and depression was calculated using the established cutoff (scores ≥8 on each subscale) indicating cases of 'possible-probable' anxiety or depression, and multivariable logistic regression analyses were performed to examine predictors of emotional distress. Among the 106 included patients, 36 (34%) scored above the cutoff (≥8) for anxiety and 24 (23%) for depression. Women were more likely to report anxiety than men (odds ratio 4.04, 95% confidence interval 1.45-11.16), and patients reporting limitations in their activity status had more than five times greater odds of reporting depression (odds ratio 6.07, 95% confidence interval 1.53-24.10). A substantial proportion of esophageal cancer patients report anxiety and/or depression prior to surgery, particularly women and those with limited activity status, which highlights a need for qualified emotional support.

Direct inoculation of Mycobacterium avium subspecies Paratuberculosis into ileocecal Peyer's patches results in colonization of the intestine in a calf model.

The objective of this study was to develop an intestinal model of Mycobacterium avium subspecies paratuberculosis (Map) infection in the calf for evaluation of mucosal pathology and local and systemic immunologic responses. Map was inoculated into Peyer's patches of young calves using a right flank surgical approach in standing calves to exteriorize the ileocecal junction. Inoculum doses ranging from 10(3) to 10(9) colony-forming units of strain K10 Map were injected through the serosal surface into Peyer's patches of the distal ileum near the ileocecal valve. Fecal samples were collected for culture from each calf weekly until termination of the study. Calves were necropsied at 7, 30, 60, and 90 days after infection, when inoculation sites, lymph nodes, spleen, and peripheral blood were collected for evaluation. Ileocecal lymph nodes were consistently colonized by Map in the 10(5) to 10(9) groups. The ileocecal valve was also colonized in 10(7) and 10(9) groups. This correlated with fecal culture results as infected calves intermittently shed Map in their feces throughout the study. Granulomatous lesions with giant cells and acid-fast bacilli at the ileocecal junction, ileocecal lymph nodes, and lamina propria of high-dose animals (10(7) and 10(9)) were identified from each time point. Flow cytometry was used to detect antigen-specific production of interferon-γ and interleukin-4 locally (ileocecal lymph node) and systemically (peripheral blood mononuclear cells), which defined distinct immunologic profiles in low-dose and high-dose calves. This study demonstrates intestinal Map infection via Peyer's patch inoculation, a novel model with many shared features of natural Map infection.