Clinical Relevance of the Tumor Location-Modified Laurén Classification System for Gastric Cancer in a Western Population.

BACKGROUND: The Tumor Location-Modified Laurén Classification (MLC) system combines Laurén histologic subtype and anatomic tumor location. It divides gastric tumors into proximal non-diffuse (PND), distal non-diffuse (DND), and diffuse (D) types. The optimum classification of patients with Laurén mixed tumors in this system is not clear due to its grouping with both diffuse and non-diffuse types in previous studies. The clinical relevance of the MLC in a Western population has not been examined. METHODS: A cohort study investigated 404 patients who underwent gastrectomy for gastric adenocarcinoma between 2005 and 2020. The classification of Laurén mixed tumors was evaluated using receiver operating characteristic (ROC) curve analysis and comparison of clinicopathologic characteristics (chi-square). Survival analysis was performed using multivariable Cox regression. RESULTS: The ROC curve analysis demonstrated a slightly higher area under the curve value for predicting survival when Laurén mixed tumors were grouped with intestinal-type rather than diffuse-type tumors (0.58 vs 0.57). Survival, tumor recurrence, and resection margin positivity in mixed tumors also was more similar to intestinal type. Distal non-diffuse tumors had the best 5-year survival (DND 64.7 % vs PND 56.1 % vs diffuse 45.1 %; p = 0.006) and were least likely to have recurrence (DND 27.0 % vs PND 34.3 % vs diffuse 48.3 %; p = 0.001). Multivariable analysis demonstrated that MLC was an independent prognostic factor for survival (PND: hazard ratio [HR], 1.64; 95 % confidence interval [CI], 1.16-2.32 vs diffuse: HR, 2.20; 95 % CI, 1.56-3.09) CONCLUSIONS: The MLC was an independent prognostic marker in this Western cohort of patients with gastric adenocarcinoma. The patients with PND and D tumors had worse survival than those with DND tumors.

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.

Microstructure design of CTAC:FA and BTAC:FA lamellar gels for optimized rheological performance utilizing automated formulation platform.

OBJECTIVES: The main objective of this paper was to optimize hair conditioner performance through variation of composition utilizing automated cosmetic formulation platform and advanced characterization techniques as well as develop understanding of how performance (wet combing and wet lubrication) of hair conditioner is affected by its rheology (i.e. yield stress) and controlled breakdown of the formulations (dilution). The experimental results show that yield stress greatly impacts rheology, stability and performance of the lamellar gels for hair conditioning. METHODS: All samples were prepared on the Chemspeed Flex Formax. A mechanical rheometer was used to measure bulk viscosity and yield stress in each sample. Dia-stron tensile tester was used to measure the lamellar gels ability to reduce combing force. Potential stronger lamellar gel network formation in the formed lamellar gels potentially leads to higher yield stress exhibited. Viscosity values were also measured after a controlled breakdown (i.e. dilution) of each sample. This was also carried out using a mechanical rheometer. RESULTS: Yield stress of the formulations was engineered through composition variation and was recorded in each system. The highest yield stress value is 251.179 Pa at a BTAC/CA ratio of 6:10, and the lowest yield stress is 50.14 Pa at a BTAC/CA ratio of 6:5. The highest yield stress value is 50.14 Pa at a CTAC/CA ratio of 6:10, and the lowest yield stress is 19.98 Pa at a CTAC/CA ratio of 2:10. The highest overall yield stress values can also be observed in the BTAC/CA system, whereas the CTAC/CA system has relatively lower yield stress values. Dilution of each formulation caused a breakdown in viscosity of each formulation with the formulations with highest yield stress maintaining higher viscosity than the other formulations. The formulations with highest yield stress in each system which also maintains the highest dilution viscosity (6% BTAC/10% CA and 6% CTAC/10% CA) have the best effect on reducing overall combing force, that is from dry hair tress to wet hair tress and after product is rinsed off. At a BTAC/CA system of ratio 6:5, there is an 89% reduction in combing force and a 95% reduction in combing force in the BTAC/CA system of ratio 6:10. At a CTAC/CA system of ratio 2:10, there is a 65% reduction in combing force and a 88% reduction in combing force in the CTAC/CA system of ratio 6:10. A 'conditioned' soft feel was observed on each hair tress as the sample was applied and after it was rinsed off. CONCLUSIONS: The overall performance of the lamellar gels for hair conditioning can be engineered through optimization of the formulation microstructure and formulation microstructure breakdown on dilution.

OBJECTIF: L'objectif principal de ce document est d'optimiser les performances des après-shampooing grâce à la variation de sa composition en utilisant une plateforme de formulation cosmétique automatisée et des techniques de caractérisation avancées, ainsi qu'en comprenant mieux comment les performances (peignage humide et lubrification humide) de l'après-shampooing sont affectées par sa rhéologie (c.-à-d. limite élastique) et répartition contrôlée des formulations (dilution). Les résultats expérimentaux montrent que la limite d'élasticité a un impact important sur la rhéologie, la stabilité et les performances des gels lamellaires pour le conditionnement des cheveux. MÉTHODÉS: Tous les échantillons ont été préparés sur le Chemspeed Flex Formax. Un rhéomètre mécanique a été utilisé pour mesurer la viscosité en vrac et la limite élastique dans chaque échantillon. Un testeur de traction Dia-stron a été utilisé pour mesurer la capacité des gels lamellaires à réduire la force de peignage. La formation d'un réseau de gel lamellaire potentiellement plus fort dans les gels lamellaires formés conduit potentiellement à une limite d'élasticité plus élevée. Les valeurs de viscosité ont également été mesurées après une dilution de chaque échantillon. Cela a également été réalisé à l'aide d'un rhéomètre mécanique. RÉSULTATS: La limite d'élasticité des formulations a été modifiée par variation de la composition et a été enregistrée dans chaque système. La limite d'élasticité la plus élevée est de 251,179 Pa à un rapport BTAC/CA de 6,10 et la limite d'élasticité la plus basse est 50,14 Pa à un rapport BTAC/CA de 6: 5. La valeur de limite d'élasticité la plus élevée est de 50,14 Pa à un rapport CTAC/CA de 6,10 et la contrainte d'élasticité la plus basse est de 19,98 Pa à un rapport CTAC/CA de 2:10. Les valeurs globales de contrainte d'écoulement les plus élevées peuvent également être observées dans le système BTAC/CA tandis que le système CTAC/CA a des valeurs de contrainte d'écoulement relativement plus faibles. La dilution de chaque formulation a provoqué une dégradation de la viscosité de chaque formulation, les formulations ayant la limite d'élasticité la plus élevée conservant une viscosité plus élevée que les autres formulations. Les formulations avec la limite d'élasticité la plus élevée dans chaque système qui maintient également la viscosité de dilution la plus élevée (6% BTAC/10% CA et 6% CTAC/10% CA) a le meilleur effet sur la réduction de la force de peignage globale, c'est-à-dire des cheveux secs aux cheveux mouillés tressées et après que le produit soit rincé. Dans un système BTAC/CA de rapport 6: 5, il y a une réduction de 89% de la force de peignage et une réduction de 95% de la force de peignage dans le système BTAC/CA de rapport 6:10. Dans un système CTAC/CA de rapport 2:10, il y a une réduction de 65% de la force de peignage et une réduction de 88% de la force de peignage dans le système CTAC/CA de rapport 6:10. Une sensation de douceur a été observée sur chaque tresse lors de l'application de l'échantillon et après le rinçage. CONCLUSION: Les performances globales des gels lamellaires pour le conditionnement des cheveux peuvent être conçues par l'optimisation de la microstructure de formulation et la décomposition de la microstructure de formulation lors de la dilution.

Health and mass unemployment events-developing a framework for preparedness and response.

BACKGROUND: Mass unemployment events are not uncommon yet the impact on health is not well recognised. There is a need for a preparedness and response framework, as exists for other events that threaten population health. METHODS: Framework informed by a narrative review of the impact of mass unemployment on health (studies published in English from 1990 to 2016), and qualitative data from 23 semi-structured interviews with individuals connected to historical national and international events, addressing gaps in published literature on lessons learnt from past responses. RESULTS: Economic and employment shock triggered by mass unemployment events have a detrimental impact on workers, families and communities. We present a public health informed response framework which includes (i) identify areas at risk, (ii) develop an early warning system, (iii) mobilise multi-sector action including health and community, (iv) provision of support across employment, finance and health (v) proportionate to need, (vi) extend support to family members and (vii) communities and (viii) evaluate and learn. CONCLUSION: Mass unemployment events have an adverse impact on the health, financial and social circumstances of workers, families, and communities. This is the first framework for action to mitigate and address the detrimental impact of mass unemployment events on population health.

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.

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.

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.

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.

Worldwide Esophageal Cancer Collaboration: pathologic staging data.

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

Worldwide Esophageal Cancer Collaboration: clinical staging data.

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection.

Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data.

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection.

Surgical resection strategy and the influence of radicality on outcomes in oesophageal cancer.

BACKGROUND: The optimal surgical approach to tumours of the oesophagus and oesophagogastric junction remains controversial. The principal randomized trial comparing transhiatal (THO) and transthoracic (TTO) oesophagectomy showed no survival difference, but suggested that some subgroups of patients may benefit from the more extended lymphadenectomy typically conducted with TTO. METHODS: This was a cohort study based on two prospectively created databases. Short- and long-term outcomes for patients undergoing THO and TTO were compared. The primary outcome measure was overall survival, with secondary outcomes including time to recurrence and patterns of disease relapse. A Cox proportional hazards model provided hazard ratios (HRs) and 95 per cent confidence intervals (c.i.), with adjustments for age, tumour stage, tumour grade, response to chemotherapy and lymphovascular invasion. RESULTS: Of 664 included patients (263 THO, 401 TTO), the distributions of age, sex and histological subtype were similar between the groups. In-hospital mortality (1·1 versus 3·2 per cent for THO and TTO respectively; P = 0·110) and in-hospital stay (14 versus 17 days respectively; P < 0·001) favoured THO. In the adjusted model, there was no difference in overall survival (HR 1·07, 95 per cent c.i. 0·84 to 1·36) or time to tumour recurrence (HR 0·99, 0·76 to 1·29) between the two operations. Local tumour recurrence patterns were similar (22·8 versus 24·4 per cent for THO and TTO respectively). No subgroup could be identified of patients who had benefited from more radical surgery on the basis of tumour location or stage. CONCLUSION: There was no difference in survival or tumour recurrence for TTO and THO.

Salmonella enterica serovar Enteritidis phage type 4 outbreak associated with eggs in a large prison, London 2009: an investigation using cohort and case/non-case study methodology.

In September 2009, an outbreak of Salmonella enterica serovar Enteritidis affected 327 of 1419 inmates at a London prison. We applied a cohort design using aggregated data from the kitchen about portions of food distributed, aligned this with individual food histories from 124 cases (18 confirmed, 106 probable) and deduced the exposures of those remaining well. Results showed that prisoners eating egg cress rolls were 26 times more likely to be ill [risk ratio 25.7, 95% confidence interval (CI) 15.5-42.8, P<0.001]. In a case/non-case multivariable analysis the adjusted odds ratio for egg cress rolls was 41.1 (95% CI 10.3-249.7, P<0.001). The epidemiological investigation was strengthened by environmental and microbiological investigations. This paper outlines an approach to investigations in large complex settings where aggregate data for exposures may be available, and led to the development of guidelines for the management of future gastrointestinal outbreaks in prison settings.

Cardiac dysfunction and N-terminal pro-B-type natriuretic peptide in exacerbations of chronic obstructive pulmonary disease.

Elevated levels of B-type natriuretic peptides among patients with exacerbations of chronic obstructive pulmonary disease (COPD) are associated with higher mortality. The pathophysiology is unclear. To establish if elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) are due to right or left heart dysfunction, we performed echocardiograms in 18 patients admitted to hospital with COPD. Elevated levels of NT-proBNP were associated with both right and left heart dysfunction and indicate that these patients have biventricular dysfunction rather than isolated right ventricular compromise.

Hospital activity and cost incurred because of unregistered patients in England: considerations for current and new commissioners.

BACKGROUND: Commissioners are responsible for providing health care for defined geographical areas. A lack of comprehensive national and local information on health needs of unregistered populations makes health service planning difficult. METHODS: A cross-sectional study using Hospital Episode Statistics to quantify the level of inpatient and outpatient activity, and associated cost by patients not registered in primary care in English NHS hospitals. Unregistered patients were defined as those without a valid GP registration, prisoners, military personnel, asylum seekers/immigrants and the homeless. RESULTS: Unregistered patients accounted for 99 615 inpatient admissions and 370 504 outpatient attendances in 2009/10, at a total cost of £242 m. Mental health accounted for 30% of all inpatient costs. The majority of unregistered patients were male and aged 20-39 years. There were high levels of activity and cost in urban local authorities (LAs) (Birmingham and London) and LAs with links to military services (Salisbury, Richmondshire, Southampton). A high total inpatient cost was attributed to trauma, general medicine and mental health specialties. A high total outpatient cost was attributed to genitourinary medicine and trauma specialties. CONCLUSIONS: Health care use by unregistered populations is an important consideration for resource allocation and planning health care services at national and local levels.

Comparison of bacterial identification by MALDI-TOF mass spectrometry and conventional diagnostic microbiology methods: agreement, speed and cost implications.

Identification of microbial pathogens still relies primarily on culture and phenotypic methods, which is labour-intensive and time-consuming. In this study, identification of bacteria with valid standard identification using BD Phoenix, API panels and other recommended procedures is compared to identification with matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) mass spectrometry using the MALDI Biotyper (Bruker Daltonics) in the setting of a routine NHS diagnostic microbiology laboratory. In total, 928 bacterial isolates obtained from blood (n=463), wounds and pus (n=208), respiratory tract (n=100), faeces (n=86) and urines (n=71) were analysed. There were 721 (77.7%) isolates with a MALDI Biotyper score > or =2.0, indicating secure genus and probable species identification; and 149 (16.1%) isolates with a score > or =1.7 and <2.0 indicating probable genus identification. The isolates with scores of > or =2.0 and > or =1.7 comprised 31 and 33 genera and 65 and 67 species, respectively. Overall, 99.4% and 99.1% of organism identifications were in agreement between the MALDI Biotyper and conventional identification at the genus level, and 89.3% and 87.8% at species level when analysing organisms with MALDI Biotyper scores > or =2.0 and > or =1.7, respectively. With many but not all organisms, identification at the genus level is sufficient; however, MALDI Biotyper separation of 208 staphylococci into Staphylococcus aureus and coagulase-negative staphylococci was always correct when scores were > or =1.7. First results were obtained after 5-10 min and analysis of a full 96-well target plate was completed in approximately 90 min. Substantial savings of between pounds 1.79 and pounds 2.56 per isolate, depending on the cost model of acquisition of the MALDI Biotyper system and number of isolates tested, would be realised when all 928 isolates were identified using the MALDI Biotyper and disk-susceptibility testing when compared to the cost for 618 Phoenix ID panels and 158 API panels and disk-susceptibility tests only (i.e., not taking into account costs incurred for identification of the remaining 152 mixed isolates). Microbial identification by MALDI Biotyper offers a rare opportunity for significant cost-neutral or even cost-saving quality improvements in medical diagnostics.

Constituent country inequalities in myocardial infarction incidence and case fatality in men and women in the United Kingdom, 1996-2005.

BACKGROUND: Understanding myocardial infarction (MI) incidence and case fatality trends across the four UK constituent countries is of importance following devolution of the government of health-care services. METHODS: Retrospective cohort study using a primary care database (5.19 million patients) examining trends in incidence of first MI and 30-day case fatality. RESULTS: From 1996 to 2005, the incidence of MI decreased in all countries, but reductions were greater in England (men, -3.1%; women, -2.8%) and Wales (men, -3.3%; women, -4.6%) than in Scotland (men, -1.9%; women, -0.6%) and Northern Ireland (men no change, women, -0.8%) (average annual percentage change). Greater reductions in England and Wales than Scotland and Northern Ireland meant a widening of north-south difference in MI incidence over the study period. Downward trends in 30-day case fatality were found in each country but less regional variation was evident (England men, -12.0%, women, -11.0%; Wales men, -18.4%, women, -12.6%; Scotland men, -9.5%, women, -9.0%; Northern Ireland men, -8.6%, women, -13.0%). CONCLUSION: From 1996 to 2005, downward trends in the incidence of first MI and 30-day case fatality were evident in each constituent country. Greater improvements in case fatality, compared with incidence, were found within each country.

Differences in the impact of precarious employment on health across population subgroups: a scoping review.

AIM: Precarious employment is known to be detrimental to health, and some population subgroups (young individuals, migrant workers, and females) are at higher risk of precarious employment. However, it is not known if the risk to poor health outcomes is consistent across population subgroups. This scoping review explores differential impacts of precarious employment on health. METHODS: Relevant studies published between 2009 and February 2019 were identified across PubMed, OVID Medline, PsycINFO, and Scopus. Articles were included if (1) they presented original data, (2) examined precarious employment within one of the subpopulations of interest, and (3) examined health outcomes. RESULTS: Searches yielded 279 unique results, of which 14 met the eligibility criteria. Of the included studies, 12 studies examined differences between gender, 3 examined the health impacts on young individuals, and 3 examined the health of migrant workers. Mental health was explored in nine studies, general health in four studies, and mortality in two studies. CONCLUSION: Mental health was generally poorer in both male and female employees as a result of precarious employment, and males were also at higher risk of mortality. There was limited evidence that met our inclusion criteria, examining the health impacts on young individuals or migrant workers.