Worldwide Esophageal Cancer Collaboration : clinical staging data

Peer reviewe

A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR)

Background: Chemoradiotherapy remains the standard of care for locally advanced rectal cancer. Efforts to intensify treatment and increase response rates have yet to yield practice changing results due to increased toxicity and/or absence of increased radiosensitization. Enadenotucirev (EnAd) is a tumour selective, oncolytic adenovirus which can be given intravenously. Pre-clinical evidence of synergy with radiation warrants further clinical testing and assessment of safety with radiation. Methods: Eligibility include histology confirmed locally advanced rectal cancer that require chemoradiation. The trial will use a Time-to-Event Continual Reassessment Model-based (TiTE-CRM) approach using toxicity and efficacy as co-primary endpoints to recommend the optimal dose and treatment schedule 30 patients will be recruited. Secondary endpoints include pathological complete response the neoadjuvant rectal score. A translational program will be based on a mandatory biopsy during the second week of treatment for ‘proof-of-concept’ and exploration of mechanism. The trial opened to recruitment in July 2019, at an expected rate of 1 per month for up to 4 years. Discussion: Chemoradiation with Enadenotucirev as a radiosensitiser in locally Advanced Rectal cancer (CEDAR) is a prospective multicentre study testing a new paradigm in radiosensitization in rectal cancer. The unique ability of EnAd to selectively infect tumour cells following intravenous delivery is an exciting opportunity with a clear translational goal. The novel statistical design will make efficient use of both toxicity and efficacy data to inform subsequent studies. Trial registration: ClinicalTrial.gov, NCT03916510. Registered 16th April 2019

IgE sensitisation in relation to flow-independent nitric oxide exchange parameters

BACKGROUND: A positive association between IgE sensitisation and exhaled NO levels has been found in several studies, but there are no reports on the compartment of the lung that is responsible for the increase in exhaled NO levels seen in IgE-sensitised subjects. METHODS: The present study comprised 288 adult subjects from the European Community Respiratory Health Survey II who were investigated in terms of lung function, IgE sensitisation (sum of specific IgE), smoking history and presence of rhinitis and asthma. Mean airway tissue concentration of NO (Caw(NO)), airway transfer factor for NO (Daw(NO)), mean alveolar concentration of NO (Calv(NO)) and fractional exhaled concentration of NO at a flow rate of 50 mL s(-1 )(FE(NO 0.05)) were determined using the extended NO analysis. RESULTS: IgE-sensitised subjects had higher levels (geometric mean) of FE(NO 0.05 )(24.9 vs. 17.3 ppb) (p < 0.001), Daw(NO )(10.5 vs. 8 mL s(-1)) (p = 0.02) and Caw(NO )(124 vs. 107 ppb) (p < 0.001) and positive correlations were found between the sum of specific IgE and FE(NO 0.05), Caw(NO )and Daw(NO )levels (p < 0.001 for all correlations). Sensitisation to cat allergen was the major determinant of exhaled NO when adjusting for type of sensitisation. Rhinitis and asthma were not associated with the increase in exhaled NO variables after adjusting for the degree of IgE sensitisation. CONCLUSION: The presence of IgE sensitisation and the degree of allergic sensitisation were related to the increase in airway NO transfer factor and the increase in NO concentration in the airway wall. Sensitisation to cat allergen was related to the highest increases in exhaled NO parameters. Our data suggest that exhaled NO is more a specific marker of allergic inflammation than a marker of asthma or rhinitis

Esophagectomy without mortality: What can surgeons do?

Introduction: Surgical resection remains the mainstay treatment for patients with localized esophageal cancer. It is, however, a complex procedure. Mortality rate used to be high, but in recent years, death rate has been reduced to below 5% in specialized centers. Methods: Outcome of esophagectomy can be improved by paying attention to (1) appropriate patient section, (2) choice of surgical techniques and their execution, and (3) optimizing perioperative care. A volume-outcome relationship is also evident. Surgeons can perform esophagectomy without mortality, but a multi-disciplinary team management is essential to achieve this goal. © 2009 The Society for Surgery of the Alimentary Tract.postprin

Magnetic resonance imaging (MRI) in rectal cancer: a comprehensive review

Magnetic resonance imaging (MRI) has established itself as the primary method for local staging in patients with rectal cancer. This is due to several factors, most importantly because of the ability to assess the status of circumferential resection margin. There are several newer developments being introduced continuously, such as diffusion-weighted imaging and imaging with 3 T. Assessment of loco-regional lymph nodes has also been investigated extensively using different approaches, but more work needs to be done. Finally, evaluation of tumours during or after preoperative treatment is becoming an everyday reality. All these new aspects prompt a review of the most recent advances and opinions. In this review, a comprehensive overview of the current status of MRI in the loco-regional assessment and management of rectal cancer is presented. The findings on MRI and their accuracy are reviewed based on the most up-to-date evidence. Optimisation of MRI acquisition and relevant regional anatomy are also presented, based on published literature and our own experience

Metalloproteinases and their inhibitors—diagnostic and therapeutic opportunities in orthopedics

Matrix metalloproteinases (MMPs) and related enzymes (ADAMs, ADAMTS) and their inhibitors control matrix turnover and function. Recent advances in our understanding of musculoskeletal conditions such as tendinopathy, arthritis, Dupuytren's disease, degenerative disc disease, and bone and soft tissue healing suggest that MMPs have prominant roles. Importantly, MMPs are amenable to inhibition by cheap, safe, and widely available drugs such as the tetracycline antibiotics and the bisphosphonates. This indicates that these MMP inhibitors, if proven effective for any novel indication, may be quickly brought into clinical practice

Postoperative complications following colonic resection for cancer are associated with impaired long-term survival

Aim: Surgery for colorectal cancer is associated with a high incidence of postoperative complications. The aim of this study was to analyse whether postoperative complications following radical resection for colorectal cancer are associated with increased recurrence rate and impaired survival. Method: Patients operated for colon cancer between 2007 and 2009 with curative intent were identified through the Swedish Colorectal Cancer Registry. The cohort was divided into three subgroups: patients who developed severe postoperative complications, patients who developed non-severe complications and patients who did not develop any complication (controls). Results: Of 6779 patients included in the study, 640 (9%) developed severe complications, 994 (15%) non-severe complications and 5145 (76%) had no complications. The 5-year overall survival rate was 60.3% in the severe complication group, 64.2% in the non-severe complication group and 72.8% in the control group (P < 0.01). The 3-year disease-free survival rate was 66.8%, 70.9% and 77.8% respectively (P < 0.01). The recurrence rate did not differ between the three groups. In multivariate analysis, both severe and non-severe complications were found to be risk factors for decreased overall survival at 5 years [hazard ratio (HR) 1.38, 95% CI 1.47–1.92, and HR 1.18, 95% CI 1.27–1.60 respectively; P < 0.05) as well as for decreased 3-year disease-free survival (HR 1.37, 95% CI 1.14–1.65, and HR 1.26, 95% CI 1.08–1.48 respectively; P < 0.05). Conclusion: Complications after colonic resection for cancer are associated with impaired 5-year overall survival and 3-year disease-free survival and exhibit more severe postoperative complications, mainly via mechanisms other than cancer recurrence

Survival after operations for ischaemic bowel disease

Objective: To find out what factors influence the outcome of operations for ischaemic bowel disease. Design: Retrospective study. Setting: University hospital, Sweden. Main outcome measures: Morbidity and mortality. Subjects: 74 patients, mean age 75 years (range 40-98), operated on for acute bowel ischaemia between 1987 and 1996. Results: A total of 75 emergency operations were done, including 42 bowel-resections, one percutaneous transluminal angioplasty, and one thrombectomy. Thirty-one patients had exploration alone because of extensive gangrene. These explorations were performed in 11 of 14 (79%) patients aged >84 years; 18 of 40 (45%) patients aged 71-84 years and 2 of 21 (9%) patients aged <71 years, (p < 0.001). Of the 14 patients over 84 years old only one survived more than 30 days, compared with 12 of 40 (30%) aged 71-84 years, and 17 of 21 (81%) younger than 71 years (p < 0.001). Operation within 6 hours of admission resulted in significantly better survival compared with operations done after more than 6 hours delay (p = 0.04). Conclusions: Advanced age was a strong risk factor for death after operation for ischaemic bowel disease, and there was a higher incidence of unresectable gangrene. Delay in surgical intervention was associated with increasing mortality