Value of MRI and diffusion-weighted MRI for the diagnosis of locally recurrent rectal cancer

OBJECTIVES: To evaluate the accuracy of standard MRI, diffusion-weighted MRI (DWI) and fusion images for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. METHODS: Forty-two patients with a clinical suspicion of recurrence underwent 1.5-T MRI consisting of standard T2-weighted FSE (3 planes) and an axial DWI (b0,500,1000). Two readers (R1,R2) independently scored the likelihood of recurrence; [1] on standard MRI, [2] on standard MRI+DWI, and [3] on T2-weighted+DWI fusion images. RESULTS: 19/42 patients had a local recurrence. R1 achieved an area under the ROC-curve (AUC) of 0.99, sensitivity 100% and specificity 83% on standard MRI versus 0.98, 100% and 91% after addition of DWI (p = 0.78). For R2 these figures were 0.87, 84% and 74% on standard MRI and 0.91, 89% and 83% with DWI (p = 0.09). Fusion images did not significantly improve the performance. Interobserver agreement was kappa0.69 for standard MRI, kappa0.82 for standard MRI+DWI and kappa0.84 for the fusion images. CONCLUSIONS: MRI is accurate for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. Addition of DWI does not significantly improve its performance. However, with DWI specificity and interobserver agreement increase. Fusion images do not improve accuracy

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

Self-expanding metal stents in malignant colonic obstruction: experiences from Sweden

<p/> <p>Background</p> <p>Acute surgery in the management of malignant colonic obstruction is associated with high morbidity and mortality. The use of self-expanding metal stents (SEMS) is an alternative method of decompressing colonic obstruction. SEMS may allow time to optimize the patient and to perform preoperative staging, converting acute surgery into elective. SEMS is also proposed as palliative treatment in patients with contraindications to open surgery. Aim: To review our experience of SEMS focusing on clinical outcome and complications. The method used was a review of 75 consecutive trials at SEMS on 71 patients based on stent-protocols and patient charts.</p> <p>Findings</p> <p>SEMS was used for palliation in 64 (85%) cases and as a bridge to surgery in 11 (15%) cases. The majority of obstructions, 53 (71%) cases, were located in the recto-sigmoid. Technical success was achieved in 65 (87%) cases and clinical decompression was achieved in 60 (80%) cases. Reasons for technical failure were inability to cannulate the stricture in 5 (7%) cases and suboptimal SEMS placement in 3 (4%) cases. Complications included 4 (5%) procedure-related bowel perforations of which 2 (3%) patients died in junction to post operative complications. Three cases of bleeding after SEMS occurred, none of which needed invasive treatment. Five of the SEMS occluded. Two cases of stent erosion were diagnosed at the time of surgery. Average survival after palliative SEMS treatment was 6 months.</p> <p>Conclusion</p> <p>Our results correspond well to previously published data and we conclude that SEMS is a relatively safe and effective method of treating malignant colonic obstruction although the risk of SEMS-related perforations has to be taken into account.</p

The Role of FeNO in Cough Management : A Randomised Controlled Trial

This abstract is funded by: Observational & Pragmatic Research Institute Pte Ltd, and Circassia Presented at thematic poster session: A34 ASTHMA CLINICAL STUDIES I Sunday 20th MayPeer reviewedPostprin

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

Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary ‘VoxTox’ research programme

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.JES was supported by Cancer Research UK through the Cambridge Cancer Centre. NGB, ASP and MG are supported by the National Institute of Health Research Cambridge Biomedical Research Centre. KH, MR AMB, EW and SJB were supported by the VoxTox Research Programme, funded by Cancer Research UK. DJN is supported by Addenbrooke’s Charitable Trust and Cancer Research UK through the Cambridge Cancer Centre. FMB was supported by the Science and Technology Facilities Council. MPDS was part supported by the VoxTox Research Programme, funded by Cancer Research UK. RJ was part supported by the VoxTox Research Programme, funded by Cancer Research UK. LS is supported by the Armstrong Trust. XC was supported by the Isaac Newton Trust. CBS acknowledges support from the EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging, the Leverhulme Trust, the EU-RISE project CHiPS and the Cantab Capital Institute for the Mathematics of Information. NT was supported by a Gates-Cambridge Scholarship, funded by the Bill and Melinda Gates Foundation, PLY and SYKS by the Singapore Government

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

Influence of primary tumour and patient factors on survival in patients undergoing curative resection and treatment for liver metastases from colorectal cancer

BACKGROUND: Resection of the primary tumour is a prerequisite for cure in patients with colorectal cancer, but hepatic metastasectomy has been used increasingly with curative intent. This national registry study examined prognostic factors for radically treated primary tumours, including the subgroup of patients undergoing liver metastasectomy. METHODS: Patients who had radical resection of primary colorectal cancer in 2009-2013 were identified in a population-based Swedish colorectal registry and cross-checked in a registry of liver tumours. Data on primary tumour and patient characteristics were extracted and prognostic impact was analysed. RESULTS: Radical resection was registered in 20 853 patients; in 38·7 per cent of those registered with liver metastases, surgery or ablation was performed. The age-standardized relative 5-year survival rate after radical resection of colorectal cancer was 80·9 (95 per cent c.i. 80·2 to 81·6) per cent, and the rate after surgery for colorectal liver metastases was 49·6 (46·0 to 53·2) per cent. Multivariable analysis identified lymph node status, multiple sites of metastasis, high ASA grade and postoperative complications after resection of the primary tumour as strong risk factors after primary resection and following subsequent liver resection or ablation. Age, sex and primary tumour location had no prognostic impact on mortality after liver resection. CONCLUSION: Lymph node status and complications have a negative impact on outcome after both primary resection and liver surgery. Older age and female sex were underrepresented in the liver surgical cohort, but these factors did not influence prognosis significantly