A meta-analysis comparing the risk of metastases in patients with rectal cancer and MRI-detected extramural vascular invasion (mrEMVI) vs mrEMVI-negative cases.

BACKGROUND: Pathological extramural vascular invasion (EMVI) is an independent prognostic factor in rectal cancer, but can also be identified on MRI-detected extramural vascular invasion (mrEMVI). We perform a meta-analysis to determine the risk of metastatic disease at presentation and after surgery in mrEMVI-positive patients compared with negative tumours. METHODS: Electronic databases were searched from January 1980 to March 2016. Conventional meta-analytical techniques were used to provide a summative outcome. Quality assessment of the studies was performed. RESULTS: Six articles reported on mrEMVI in 1262 patients. There were 403 patients in the mrEMVI-positive group and 859 patients in the mrEMVI-negative group. The combined prevalence of mrEMVI-positive tumours was 0.346(range=0.198-0.574). Patients with mrEMVI-positive tumours presented more frequently with metastases compared to mrEMVI-negative tumours (fixed effects model: odds ratio (OR)=5.68, 95% confidence interval (CI) (3.75, 8.61), z=8.21, df=2, P<0.001). Patients who were mrEMVI-positive developed metastases more frequently during follow-up (random effects model: OR=3.91, 95% CI (2.61, 5.86), z=6.63, df=5, P<0.001). CONCLUSIONS: MRI-detected extramural vascular invasion is prevalent in one-third of patients with rectal cancer. MRI-detected extramural vascular invasion is a poor prognostic factor as evidenced by the five-fold increased rate of synchronous metastases, and almost four-fold ongoing risk of developing metastases in follow-up after surgery.

How Should Imaging Direct/Orient Management of Rectal Cancer?

Modern rectal cancer management is dependent on preoperative staging, and radiological assessment is a crucial part of this process. Imaging must provide sufficient information to guide preoperative decision-making that is reliable and reproducible. Different methods have been used for local staging; however, magnetic resonance imaging (MRI) has shown to be the most reliable tool for this purpose. MRI offers prognostic information about the patients and guides the decision between neoadjuvant treatment and total mesorectal excision alone. Also, not only the initial staging but also restaging by MRI can provide significant information regarding tumor response that is essential when considering alternative approaches.

Magnetic Resonance Tumor Regression Grade and Residual Mucosal Abnormality as Predictors for Pathological Complete Response in Rectal Cancer Postneoadjuvant Chemoradiotherapy.

BACKGROUND: Pathological complete response after chemoradiotherapy for rectal cancer occurs in 10% to 30% of patients. The best method to identify such patients remains unclear. Clinical assessment of residual mucosal abnormality is considered the most accurate method. In our institution, magnetic resonance tumor regression grade is performed as routine to assess response. OBJECTIVE: The purpose of this study was to compare the sensitivity of magnetic tumor regression grade against residual mucosal abnormality in detecting patients with a pathological complete response. DESIGN: Magnetic tumor regression grade scores from reported posttreatment MRI scans were documented. Magnetic tumor regression grade 1 to 3 was defined as likely to predict complete or near complete response. Gross appearances of the mucosa were derived from histopathology reports and used as a surrogate for clinical assessment (previously validated). Final histopathological staging was used to determine response. SETTINGS: The study was conducted at Royal Marsden National Health Service Trust, United Kingdom. PATIENTS: A total of 143 patients with rectal adenocarcinoma, diagnosed between September 1, 2009, and September 1, 2013, who received neoadjuvant chemoradiotherapy before curative surgery were included. MAIN OUTCOME MEASURES: The sensitivity of magnetic tumor regression grade and residual mucosal abnormality in detecting patients with pathological complete response were measured RESULTS: : Eighteen patients had a pathological complete response. Seventeen were detected using magnetic resonance tumor regression grade 1 to 3, with sensitivity 94% (95% CI, 0.74-0.99), and 10 were detected using residual mucosal abnormality, with sensitivity 62% (95% CI, 0.38-0.81). There was no statistical difference between the false positive rates for either method. Magnetic tumor regression grade identified 10 times more patients with a pathological complete response (diagnostic OR = 10.2 (95% CI, 1.30-73.73)) compared with clinical assessment with RMA. LIMITATIONS: Residual mucosal abnormality was used as a surrogate marker for endoscopic appearances. CONCLUSIONS: Most patients with rectal cancer who have a pathological complete response do not manifest a complete response at the mucosal level. Magnetic tumor regression grade is able to identify 10 times more patients than clinical assessment, with no significant compromise in the false positive rate.

The molecular mechanisms of vascular restenosis: Which genes are crucial?

Many patients with coronary heart disease undergo percutaneous transluminal coronary angioplasty (PTCA) to improve myocardial tissue perfusion. However, a major complication after revascularisation procedures is restenosis of the injured artery. The molecular mechanism involved is not fully elucidated and no successful treatment is currently available. Animal models are preliminary tools that can help improve our understanding of the pathogenesis and treatment of restenosis in humans. Attracted by well-defined genetic systems, a number of investigators began to use the mouse as an experimental system for restenosis research. They demonstrated that several stages involved in this process include thrombus formation, inflammatory cell infiltration and smooth muscle cell (SMC) accumulation to form neointimal lesions. By using transgenic and knockout mice a number of genes related to these processes have been found to play a major role in mediating lesion formation, e.g. the plasminogen system, matrix metalloproteinases (MMP), adhesion molecules, cytokines and signal transducers. This review will not attempt to cover all aspects of related genes or molecules, but will rather focus on several groups of genes, by which the major progress in understanding the mechanisms of the disease has been made. The information obtained by using animal models could be essential for a better understanding of the pathogenesis of restenosis in humans and to provide a basis for therapeutic intervention.

Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales.

AIM: To define good and poor regression using pathology and magnetic resonance imaging (MRI) regression scales after neo-adjuvant chemotherapy for rectal cancer. METHODS: A systematic review was performed on all studies up to December 2015, without language restriction, that were identified from MEDLINE, Cochrane Controlled Trials Register (1960-2015), and EMBASE (1991-2015). Searches were performed of article bibliographies and conference abstracts. MeSH and text words used included "tumour regression", "mrTRG", "poor response" and "colorectal cancers". Clinical studies using either MRI or histopathological tumour regression grade (TRG) scales to define good and poor responders were included in relation to outcomes [local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and overall survival (OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome measures. RESULTS: Quantitative data (prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data (LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemo-radiotherapy (CRT) was 37.7% (95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale (mrTRG). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR 0%-1.8%, DR 0%-11.6%, DFS 78.4%-86.7%, and OS 77.4%-88.2%. A poor response on MRI (mrTRG 4,5) resulted in 5-year LR 4%-29%, DR 9%, DFS 31%-59% and OS 27%-68%. The 5-year outcomes with a good response on MRI (mrTRG 1,2 and 3) were LR 1%-14%, DR 3%, DFS 64%-83% and OS 72%-90%. CONCLUSION: For histopathology regression assessment, Mandard 1, 2/Dworak 3, 4 should be used for good response and Mandard 3, 4, 5/Dworak 0, 1, 2 for poor response. MRI indicates good and poor response by mrTRG1-3 and mrTRG4-5, respectively.

Laparoscopic surgery for rectal cancer.

Laparoscopic surgery for colonic cancer is a safe and established alternative to traditional open colectomy. The potential advantages of shorter length of stay, faster recovery and fewer operative complications are well documented. The last 5 years has seen an increase in the number of laparoscopic colorectal operations as more surgeons learn this technique. Short and medium term results have been encouraging with respect to oncological outcomes. However, laparoscopic surgery for rectal cancer remains a contentious issue. The increased complexity of operating within the confines of the pelvis and the greater risk of oncological compromise, have led to some surgeons urging caution. We present the challenges associated with laparoscopic rectal cancer surgery and explain that appropriate patient selection, surgical planning and laparoscopic experience are the key to successful outcomes.