Oesophagopleural fistula after pneumonectomy: A systematic review and case series.

INTRODUCTION: There is a paucity of data on the optimal management of oesophagopleural fistula (OPF) following pneumonectomy. The current published literature is limited to case reports and small case series. Although rare, OPF can have a significant impact on both the morbidity and mortality of patients. METHODS: Two cases of OPF managed at our institution were reported. A systematic review was then conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance concerning OPF following pneumonectomy. Demographic, operative and management data were analysed. FINDINGS: Systematic review-identified data pertaining to 59 patients from 31 papers was collated. Median patient age was 59.5 years with pneumonectomy performed typically for malignancy (68%) or tuberculosis (19%). Median time from pneumonectomy to a diagnosis of OPF was 12.5 months. Twenty-five per cent of the patients had a synchronous bronchopleural fistula. Management of OPF in this setting is heterogenous. Conservative management was often reserved for asymptomatic or unfit patients. The remainder underwent endoscopic or surgical correction of the fistulae or a combination of the two with varying outcomes. Median follow-up was 18 months. All-cause mortality was 31% (18/59) with a median duration from pneumonectomy to death of 35 days (range 1-1,095). CONCLUSIONS: Major heterogeneity of management for this rare complication hinders the introduction of standardised guidance of post-pneumonectomy OPF. Surgical and endoscopic intervention is feasible and can be successful in specialist centres. Adopting an multidisciplinary team approach involving both oesophagogastric and thoracic surgery teams and the introduction of a registry database of postoperative complications are likely to yield optimal outcomes.

A preoperative predictive tool to assess the need for staging laparoscopy in oesophagogastric cancer patients.

INTRODUCTION: Staging laparoscopy (SL) has become commonplace in the preoperative staging pathway for oesophagogastric (OG) cancer. SL is often performed before curative treatment to examine for macroscopic peritoneal metastases (PM) or positive peritoneal cytology (PPC). The aim of this study was to develop an objective risk scoring system to predict both PM and PPC at SL. METHODS: A prospectively collected and maintained database of all OG cancer patients treated between 2006 and 2020 was reviewed. Univariate and multivariate analyses were performed to identify risk factors for both PM and PPC at SL. A risk score was produced for both PM and PPC, and then validated internally. RESULTS: Among 968 patients who underwent SL, 96 (9.9%) had PM and 81 (8.4%) had PPC at SL. Tumour site (p < 0.001), computed tomography (CT) T stage (p < 0.001) and N stage (p = 0.029) were significantly associated with PM at SL (p < 0.001). Tumour site (p < 0.001), biopsy histology (p = 0.041), CT T stage (p < 0.001) and N stage (p < 0.001) were significantly associated with PPC. The risk scoring model for PM included cancer site and CT T stage. This was successfully tested on the validation set (area under the receiver operating characteristic [AUROC] = 0.730). The risk scoring model for PPC included cancer site, CT T and N stage. This was successfully tested on the validation set (AUROC = 0.773). CONCLUSIONS: The current risk scores are valid tools with which to predict the risk PM and PPC in patients undergoing SL for OG cancer and may help to avoid subjecting patients to unnecessary SL.

The underwater soundscape of the North Sea.

As awareness on the impact of anthropogenic underwater noise on marine life grows, underwater noise measurement programs are needed to determine the current status of marine areas and monitor long-term trends. The Joint Monitoring Programme for Ambient Noise in the North Sea (JOMOPANS) collaborative project was funded by the EU Interreg to collect a unique dataset of underwater noise levels at 19 sites across the North Sea, spanning many different countries and covering the period from 2019 to 2020. The ambient noise from this dataset has been characterised and compared - setting a benchmark for future measurements in the North Sea area. By identifying clusters with similar sound characteristics in three broadband frequency bands (25-160 Hz, 0.2-1.6 kHz, and 2-10 kHz), geographical areas that are similarly affected by sound have been identified. The measured underwater sound levels show a persistent and spatially uniform correlation with wind speed at high frequencies (above 1 kHz) and a correlation with the distance from ships at mid and high frequencies (between 40 Hz and 4 kHz). Correlation with ocean current velocity at low frequencies (up to 200 Hz), which are susceptible to nonacoustic contamination by flow noise, was also evaluated. These correlations were evaluated and simplified linear scaling laws for wind and current speeds were derived. The presented dataset provides a baseline for underwater noise measurements in the North Sea and shows that spatial variability of the dominant sound sources must be considered to predict the impact of noise reduction measures.

COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Core outcome set for surgical trials in gastric cancer (GASTROS study): international patient and healthcare professional consensus.

BACKGROUND: Surgery is the primary treatment that can offer potential cure for gastric cancer, but is associated with significant risks. Identifying optimal surgical approaches should be based on comparing outcomes from well designed trials. Currently, trials report different outcomes, making synthesis of evidence difficult. To address this, the aim of this study was to develop a core outcome set (COS)-a standardized group of outcomes important to key international stakeholders-that should be reported by future trials in this field. METHODS: Stage 1 of the study involved identifying potentially important outcomes from previous trials and a series of patient interviews. Stage 2 involved patients and healthcare professionals prioritizing outcomes using a multilanguage international Delphi survey that informed an international consensus meeting at which the COS was finalized. RESULTS: Some 498 outcomes were identified from previously reported trials and patient interviews, and rationalized into 56 items presented in the Delphi survey. A total of 952 patients, surgeons, and nurses enrolled in round 1 of the survey, and 662 (70 per cent) completed round 2. Following the consensus meeting, eight outcomes were included in the COS: disease-free survival, disease-specific survival, surgery-related death, recurrence, completeness of tumour removal, overall quality of life, nutritional effects, and 'serious' adverse events. CONCLUSION: A COS for surgical trials in gastric cancer has been developed with international patients and healthcare professionals. This is a minimum set of outcomes that is recommended to be used in all future trials in this field to improve trial design and synthesis of evidence.

Urgent surgical repair of symptomatic Bochdalek hernia containing an intrathoracic kidney.

Bochdalek hernias rarely contain an intrathoracic kidney, and there are few reports of their operative repair. A woman presented with progressive dyspnoea limiting her quality of life. Imaging showed a Bochdalek hernia containing omentum, large bowel and the left kidney. The woman was unexpectedly admitted to the intensive care unit with respiratory failure secondary to gallstone pancreatitis whilst awaiting elective repair of her hernia. Surgical repair of the hernia was performed via laparotomy with cholecystectomy to treat both problems. The woman recovered well and is independently mobile without any exertional dyspnoea.

Minimally invasive techniques for transthoracic oesophagectomy for oesophageal cancer: systematic review and network meta-analysis.

BACKGROUND: Oesophagectomy is a demanding operation that can be performed by different approaches including open surgery or a combination of minimal access techniques. This systematic review and network meta-analysis aimed to evaluate the clinical outcomes of open, minimally invasive and robotic oesophagectomy techniques for oesophageal cancer. METHODS: A systematic literature search was conducted for studies reporting open oesophagectomy, laparoscopically assisted oesophagectomy (LAO), thoracoscopically assisted oesophagectomy (TAO), totally minimally invasive oesophagectomy (MIO) or robotic MIO (RAMIO) for oesophagectomy. A network meta-analysis of intraoperative (operating time, blood loss), postoperative (overall complications, anastomotic leaks, chyle leak, duration of hospital stay) and oncological (R0 resection, lymphadenectomy) outcomes, and survival was performed. RESULTS: Ninety-eight studies involving 32 315 patients were included in the network meta-analysis (open 17 824, 55·2 per cent; LAO 1576, 4·9 per cent; TAO 2421 7·5 per cent; MIO 9558, 29·6 per cent; RAMIO 917, 2·8 per cent). Compared with open oesophagectomy, both MIO and RAMIO were associated with less blood loss, significantly lower rates of pulmonary complications, shorter duration of stay and higher lymph node yield. There were no significant differences between surgical techniques in surgical-site infections, chyle leak, and 30- and 90-day mortality. MIO and RAMIO had better 1- and 5-year survival rates respectively compared with open surgery. CONCLUSION: Minimally invasive and robotic techniques for oesophagectomy are associated with reduced perioperative morbidity and duration of hospital stay, with no compromise of oncological outcomes but no improvement in perioperative mortality.

ANTECEDENTES: La esofaguectomía es una operación muy exigente que puede ser realizada a través de diferentes abordajes que incluyen la cirugía abierta o una combinación de técnicas con acceso mínimamente invasivo. Esta revisión sistemática y metaanálisis en red se propuso evaluar los resultados clínicos de la esofaguectomía abierta y de las técnicas de esofaguectomía mínimamente invasiva y robótica para el cáncer de esófago. MÉTODOS: Se llevó a cabo una búsqueda sistemática de la bibliografía de estudios que describiesen esofaguectomía abierta, esofaguectomía asistida por laparoscopia (laparoscopic assisted oesophagectomy, LAO), esofaguectomía asistida por toracoscopia (thoracoscopic assisted oesophagectomy, TAO), esofaguectomía totalmente mínimamente invasiva (totally minimally invasive oesophagectomy, MIO) o MIO robótica (RAMIO). Se realizó un mataanálisis en red de resultados intraoperatorios (tiempo operatorio, pérdida de sangre), postoperatorios (complicaciones globales, fuga anastomótica, quilotórax, duración estancia hospitalaria), oncológicos (resección R0, linfadenectomía) y supervivencia. RESULTADOS: Se incluyeron 98 estudios con 32.296 pacientes en el metaanálisis en red (abierta: n = 17.824, 55%; LAO: n = 1.576, 5%; TAO: n = 2.421, 7%; MIO: n = 9.558, 30%; RAMIO: n = 917, 3%). En comparación con la vía abierta, tanto MIO y RAMIO se asociaron con menos pérdidas hemáticas, tasas significativamente menores de complicaciones pulmonares, estancia más corta y obtención de un mayor número de ganglos linfáticos. No hubo diferencias significativas entre las técnicas quirúrgicas en las infecciones del sitio quirúrgico, quilotórax y mortalidad a los 30 y 90 días. MIO y RAMIO se asociaron con mejores tasas de supervivencia a 1 y 5 años respectivamente, en comparación con la cirugía abierta. CONCLUSIÓN: Las técnicas mínimamente invasivas y robótica para la esofaguectomía se asociaron con menor morbilidad postoperatoria y estancia hospitalaria, sin comprometer los resultados oncológicos, pero sin mejoría en la mortalidad perioperatoria.

Atenolol in cats with subclinical hypertrophic cardiomyopathy: a double-blind, placebo-controlled, randomized clinical trial of effect on quality of life, activity, and cardiac biomarkers.

OBJECTIVE: To compare quality of life (QOL) and activity measures between healthy control cats and cats with subclinical hypertrophic cardiomyopathy (HCM), and to evaluate the effect of oral atenolol therapy on QOL, activity, and circulating biomarkers in cats with subclinical HCM. ANIMALS: Thirty-two client-owned cats with subclinical HCM and 27 healthy control cats. METHODS: Owner responses to a QOL questionnaire, circulating cardiac biomarker concentrations, and accelerometer-based activity measures were compared prospectively in cats with and without HCM, and in cats with HCM before and after treatment with oral atenolol (6.25 mg/cat q 12 h) for 6 months. RESULTS: Owner-assessed activity of daily living score was lower in cats with HCM than in cats in controls (p=0.0420). No differences were identified between control cats and cats with HCM for any activity variable. Compared with placebo, treatment with atenolol was associated with a lower baseline-adjusted mean ± SD heart rate (157 ± 30 vs. 195 ± 20 bpm; p=0.0001) and rate-pressure product (22,446 ± 6,237 vs. 26,615 ± 4,623 mmHg/min; p=0.0146). A treatment effect of atenolol on QOL or activity was not demonstrated. CONCLUSIONS: This study failed to identify an effect of subclinical HCM on owner-assessed QOL or activity or a treatment effect of atenolol on these variables at the dosage evaluated. These findings do not support a treatment benefit of atenolol for the goal of symptom reduction in cats with subclinical HCM.

Anastomotic techniques for oesophagectomy for malignancy: systematic review and network meta-analysis.

BACKGROUND: Current evidence on the benefits of different anastomotic techniques (hand-sewn (HS), circular stapled (CS), triangulating stapled (TS) or linear stapled/semimechanical (LSSM) techniques) after oesophagectomy is conflicting. The aim of this study was to evaluate the evidence for the techniques for oesophagogastric anastomosis and their impact on perioperative outcomes. METHODS: This was a systematic review and network meta-analysis. PubMed, EMBASE and Cochrane Library databases were searched systematically for randomized and non-randomized studies reporting techniques for the oesophagogastric anastomosis. Network meta-analysis of postoperative anastomotic leaks and strictures was performed. RESULTS: Of 4192 articles screened, 15 randomized and 22 non-randomized studies comprising 8618 patients were included. LSSM (odds ratio (OR) 0·50, 95 per cent c.i. 0·33 to 0·74; P = 0·001) and CS (OR 0·68, 0·48 to 0·95; P = 0·027) anastomoses were associated with lower anastomotic leak rates than HS anastomoses. LSSM anastomoses were associated with lower stricture rates than HS anastomoses (OR 0·32, 0·19 to 0·54; P < 0·001). CONCLUSION: LSSM anastomoses after oesophagectomy are superior with regard to anastomotic leak and stricture rates.

ANTECEDENTES: La evidencia actual sobre los beneficios de diferentes técnicas de anastomosis, incluyen la técnica manual (hand-sewn, HS), la sutura mecánica circular (circular stapled, CS), la sutura mecánica triangular (triangular stapler, TS) o la sutura mecánica lineal/semi-mecánica (linear stapler/semi-mechanical., LSSM) tras una esofaguectomía es contradictoria. El objetivo de este estudio fue evaluar la evidencia referente a las técnicas de anastomosis esofagogástrica (oesophagogastric, OG) y su impacto sobre los resultados perioperatorios. MÉTODOS: Se efectuó una revisión sistemática y metaanálisis en red, basados en una búsqueda sistemática en las bases de datos PubMed, EMBASE y Cochrane Library de estudios aleatorizados y no aleatorizados que describiese técnicas para la anastomosis OG. Se llevó a cabo un metaanálisis en red para los resultados de fugas anastomóticas y estenosis postoperatorias. RESULTADOS: De los 4.192 artículos revisados, se incluyeron 15 estudios aleatorizados y 22 no aleatorizados con un total de 8.618 pacientes. Las anastomosis con LSSM (razón de oportunidades, odds ratio, OR 0,49, i.c. del 95%: 0,33-0,74, P = 0,001) y las anastomosis con CS (OR 0,68, i.c. del 95%: 0.48-0,95, P = 0,027) se asociaron con tasas de fugas anastomóticas más bajas que las anastomosis con HS. Las anastomosis con LSSM se asociaron con unas tasas más bajas de estenosis (OR 0,15, i.c. del 95%: 0,08-0,28, P < 0,001), frente a las anastomosis con TS y HS. CONCLUSIONES: Las anastomosis con LSSM después de esofaguectomía son superiores en relación a las tasas de fugas anastomóticas y estenosis.

Impact of postoperative complications on survival after oesophagectomy for oesophageal cancer.

BACKGROUND: Recent evidence suggests that complications after oesophagectomy may decrease short- and long-term survival of patients with oesophageal cancer. This study aimed to analyse the impact of complications on survival in a Western cohort. METHODS: Complications after oesophagectomy were recorded for all patients operated on between January 2006 and February 2017, with severity defined using the Clavien-Dindo classification. Associations between complications and overall and recurrence-free survival were assessed using univariable and multivariable Cox regression models. RESULTS: Of 430 patients, 292 (67·9 per cent) developed postoperative complications, with 128 (39·8 per cent) classified as Clavien-Dindo grade III or IV. No significant associations were detected between Clavien-Dindo grade and either tumour (T) (P = 0·071) or nodal (N) status (P = 0·882). There was a significant correlation between Clavien-Dindo grade and ASA fitness grade (P = 0·032). In multivariable analysis, overall survival in patients with Clavien-Dindo grade I complications was similar to that in patients with no complications (hazard ratio (HR) 0·97, P = 0·915). However, patients with grade II and IV complications had significantly shorter overall survival than those with no complications: HR 1·64 (P = 0·007) and 1·74 (P = 0·013) respectively. CONCLUSION: Increasing severity of complications after oesophagectomy was associated with decreased overall survival. Prevention of complications should improve survival.

Machine learning to predict early recurrence after oesophageal cancer surgery.

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

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

Study protocol for a multicenter prospective cohort study on esophagogastric anastomoses and anastomotic leak (the Oesophago-Gastric Anastomosis Audit/OGAA).

Esophagectomy is a mainstay in curative treatment for esophageal cancer; however, the reported techniques and outcomes can vary greatly. Thirty-day mortality of patients with an intact anastomosis is 2-3% as compared to 17-35% in patients who have an anastomotic leak. The subsequent management of leaks postesophagectomy has great global variability with little consensus on a gold standard of practice. The aim of this multicentre prospective audit is to analyze current techniques of esophagogastric anastomosis to determine the effect on the anastomotic leak rate. Leak rates and leak management will be assessed to determine their impact on patient outcomes. A 12-month international multicentre prospective audit started in April 2018 and is coordinated by a team from the West Midlands Research Collaborative. This will include patients undergoing esophagectomy over 9 months and encompassing a 90-day follow-up period. A pilot data collection period occurred at four UK centers in 2017 to trial the data collection form. The audit standards will include anastomotic leak and the conduit necrosis rate should be less than 13% and major postoperative morbidity (Clavien-Dindo Grade III or more) should be less than 35%. The 30-day mortality rate should be less than 5% and the 90-day mortality rate should be less than 8%. This will be a trainee-led international audit of esophagectomy practice. Key support will be given by consultant colleagues and anesthetists. Individualized unit data will be distributed to the respective contributing sites. An overall anonymized report will be made available to contributing units. Results of the audit will be published in peer-reviewed journals with all collaborators fully acknowledged. The key information and results from the audit will be disseminated at relevant scientific meetings.

A Modified AUGIS Delphi Process to Establish Future Research Priorities in Benign Upper Gastrointestinal Surgery.

BACKGROUND: The aim of our study was to use a modified Delphi process to determine the research priorities amongst benign upper gastrointestinal (UGI) surgeons in the United Kingdom. METHODS: Delphi methodology may be utilised to develop consensus opinion amongst a group of experts. Members of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland were invited to submit individual research questions via an online survey (phase I). Two rounds of prioritisation by multidisciplinary expert healthcare professionals (phase II and III) were completed to determine a final list of high-priority research questions. RESULTS: Four hundred and twenty-seven questions were submitted in phase I, and 51 with a benign UGI focus were taken forward for prioritisation in phase II. Twenty-eight questions were ranked in phase III. A final list of 11 high-priority questions had an emphasis on acute pancreatitis, Barrett's oesophagus and benign biliary disease. CONCLUSION: A modified Delphi process has produced a list of 11 high-priority research questions in benign UGI surgery. Future studies and awards from funding bodies should reflect this consensus list of prioritised questions in the interest of improving patient care and encouraging collaborative research.

Meta-analysis of the influence of a positive circumferential resection margin in oesophageal cancer.

Background: The evidence regarding the prognostic impact of a positive circumferential resection margin (CRM) in oesophageal cancer is conflicting, and there is global variability in the definition of a positive CRM. The aim of this study was to determine the impact of a positive CRM on survival in patients undergoing oesophagectomy for oesophageal cancer. Methods: A systematic review and meta-analysis was performed. PubMed and Embase databases were searched for articles to May 2018 examining the effect of a positive CRM on survival. Cohort studies written in English were included. Meta-analyses of univariable and multivariable hazard ratios (HRs) were performed using both Royal College of Pathologists (RCP) and College of American Pathologists (CAP) criteria. Risk of bias was assessed using the Newcastle-Ottawa Scale. Egger regression, and Duval and Tweedie trim-and-fill statistics were used to assess publication bias. Results: Of 133 studies screened, 29 incorporating 6142 patients were finally included for analysis. Pooled univariable HRs for overall survival in patients with a positive CRM were 1·68 (95 per cent c.i. 1·48 to 1·91; P < 0·001) and 2·18 (1·84 to 2·60; P < 0·001) using RCP and CAP criteria respectively. Subgroup analyses demonstrated similar results for patients by T category, neoadjuvant therapy and tumour type. Pooled HRs from multivariable analyses suggested that a positive CRM was independently predictive of a worse overall survival (RCP: 1·41, 1·21 to 1·64, P < 0·001; CAP: 2·37, 1·60 to 3·51, P < 0·001). Conclusion: A positive CRM is associated with a worse prognosis regardless of classification system, T category, tumour type or neoadjuvant therapy.

Meeting Report: WHO consultation on considerations for regulatory expectations of Zika virus vaccines for use during an emergency.

On 1 February 2016, in the context of the ongoing Zika virus epidemic, the WHO declared that the recently reported clusters of microcephaly and other neurological disorders constituted a Public Health Emergency of International Concern (PHEIC). In response, WHO in collaboration with UNICEF and a working group of independent subject matter experts developed a Zika virus vaccine Target Product Profile (TPP) for use in an emergency, or in a future outbreak scenario. The drafting process of the Zika virus vaccine TPP included the opportunity for public comment, as well as consultation with epidemiologists, flavivirus vaccine subject matter experts, vaccine developers and global regulators to consider the regulatory expectations and potential emergency use pathways for a vaccine with the characteristics described in the TPP. This report summarizes an expert consultation held 6-7 June 2016 on the regulatory considerations for a Zika vaccine for emergency use.

Does the Pittsburgh Severity Score predict outcome in esophageal perforation?

Esophageal perforation is an uncommon and challenging surgical emergency associated with high rates of morbidity and mortality. At present, no consensus exists on optimal management of the condition. The Pittsburgh Severity Score (PSS) is a tool intended to stratify perforation severity and guide treatment. However, there is a paucity of literature examining the validity of the score or its application in a UK population. This study aims to validate the PSS and explore its use in stratifying patients with esophageal perforation into distinct subgroups with differential outcomes in an independent UK study population.All patients treated for esophageal perforation at Queen Elizabeth Hospital, Birmingham between September 2003 and October 2017 were included in this study. Cases were identified using a combination of ICD-10 and OPCS informatics search codes and prospective case collection. Data relating to the clinical presentation, diagnosis, management, and outcome of cases were recorded using a preformed data collection form. PSS predictive performance was assessed against five outcomes: rates of post-perforation and post-operative complications, in-hospital mortality, length of intensive care (ICU/HDU) stay, and total length of hospital stay.A total of 87 cases were identified, consisting of 48 (55%) iatrogenic perforations, 24 (28%) cases of spontaneous (Boerhaave's) perforation, and 15 perforations due to other etiologies (17%). Operative management was favored in this series, with 47% of all perforations being treated surgically. Overall in-hospital mortality was 13%, coupled with a median length of hospital stay of 24 days (interquartile range [IQR]: 12-49), of which a median of 2 days was spent in intensive care facilities (IQR: 0-14). A total of 46% of patients developed post-perforation complications, with 59% of the operatively managed cohort developing complications post-operatively.The PSS was not found to be significantly predictive of post-perforation complications (area under the ROC curve [AUROC]: 0.62, p = 0.053) or in-hospital mortality (AUROC: 0.69, p = 0.057) for the cohort as a whole. However, a subgroup analysis found the accuracy of the PSS to vary considerably by etiology, being significantly predictive of post-perforation complications within the subgroup of Boerhaave's perforations (AUROC: 0.86, p = 0.004).In conclusion, we found that the PSS has some utility in stratifying esophageal perforation severity and predicting specific patient outcomes. However, it appears to be of more value when applied to the subgroup of patients with Boerhaave's perforations.

Radial forearm free flap as the last resort for oesophageal reconstruction.

Strategies for oesophageal reconstruction following resection vary according to the nature of the pathology encountered, patient factors and surgeon preference. However, reconstruction in patients with multiple previous failed attempts poses specific management challenges. We present the case of a 61-year-old man who underwent oesophageal reconstruction with a radial forearm flap as a last resort.

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

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

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].