Extramural venous invasion is a potential imaging predictive biomarker of neoadjuvant treatment in rectal cancer

BACKGROUND: Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer and identified on magnetic resonance imaging (MRI) (mrEMVI). The clinical relevance of improvement in mrEMVI following neoadjuvant therapy is unknown. This study aimed to demonstrate that regression of mrEMVI following neoadjuvant chemoradiotherapy (CRT) results in improved outcomes and mrEMVI can be used as an imaging biomarker METHODS: Retrospective analysis of prospectively collected data was conducted examining the staging and post-treatment MRIs of patients who had presented with EMVI-positive rectal cancer. All patients had undergone neoadjuvant CRT and curative surgery. Changes in mrEMVI were graded with a new MRI-based TRG scale–mr-vTRG; and related to disease-free survival (DFS). The study fulfilled Reporting Recommendations for Tumour Marker Prognostic Studies criteria for biomarkers. RESULTS: Sixty-two patients were included. Thirty-five patients showed more than 50% fibrosis of mrEMVI (mr-vTRG 1-3); 3-year DFS 87.8% and 9% recurrence. Twenty-seven patients showed less than 50% fibrosis (mr-vTRG 4-5); 3-year DFS 45.8% with 44% recurrence – P<0.0001. On multivariate Cox-regression, only mr-vTRG 4-5 increased risk of disease recurrence – HR=5.748. CONCLUSION: Patients in whom there has been a significant response of EMVI to CRT show improved DFS. Those patients with poor response should be considered for intensive treatment. As an imaging biomarker in rectal cancer, mrEMVI can be used

Extramural venous invasion is a potential imaging predictive biomarker of neoadjuvant treatment in rectal cancer

BACKGROUND: Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer and identified on magnetic resonance imaging (MRI) (mrEMVI). The clinical relevance of improvement in mrEMVI following neoadjuvant therapy is unknown. This study aimed to demonstrate that regression of mrEMVI following neoadjuvant chemoradiotherapy (CRT) results in improved outcomes and mrEMVI can be used as an imaging biomarker METHODS: Retrospective analysis of prospectively collected data was conducted examining the staging and post-treatment MRIs of patients who had presented with EMVI-positive rectal cancer. All patients had undergone neoadjuvant CRT and curative surgery. Changes in mrEMVI were graded with a new MRI-based TRG scale–mr-vTRG; and related to disease-free survival (DFS). The study fulfilled Reporting Recommendations for Tumour Marker Prognostic Studies criteria for biomarkers. RESULTS: Sixty-two patients were included. Thirty-five patients showed more than 50% fibrosis of mrEMVI (mr-vTRG 1-3); 3-year DFS 87.8% and 9% recurrence. Twenty-seven patients showed less than 50% fibrosis (mr-vTRG 4-5); 3-year DFS 45.8% with 44% recurrence – P<0.0001. On multivariate Cox-regression, only mr-vTRG 4-5 increased risk of disease recurrence – HR=5.748. CONCLUSION: Patients in whom there has been a significant response of EMVI to CRT show improved DFS. Those patients with poor response should be considered for intensive treatment. As an imaging biomarker in rectal cancer, mrEMVI can be used

Functional outcomes following ileal pouch-anal anastomosis (IPAA) in older patients: a systematic review

Aim Ileal pouch-anal anastomosis (IPAA) is performed in ulcerative colitis or familial adenomatous polyposis with a view to restoration of GI continuity and prevention of permanent faecal diversion. Debate exists as to its safety in older patients. This review aims to assess functional outcomes and safety of restorative proctocolectomy (RPC) in older compared to younger patients. Methods Literature search was performed for age-stratified studies which assessed functional outcomes of IPAA. Twelve papers were included overall. Patients were categorized into ‘older’ and ‘younger’ groups. Analysis was split into three separate parts: 1. Age cut-off of 50 ± 5 years (with sensitivity analysis); 2. Age cut-off of 65 ± years; 3. Long-term outcomes (>10 years). Results With an age cut-off of 50 years (4327 versus 513 patients), complication rates were comparable with the exception of an increased rate of small-bowel obstruction in the younger patients (p = 0.034). At 1 year, 24-h stool frequency was significantly higher in the older patient group (p < 0.0001). Daytime (p < 0.0001) and night-time (p < 0.0001) incontinence rates were also significantly higher in older patients. Overall, function deteriorated with time across all ages; however, after 10 years, there was no significant difference in incontinence rates between age groups. Dehydration and electrolyte loss was a significant problem in patients over 65 (p < 0.0001). Despite differences in postoperative function, quality of life was comparable between groups; however, only a few studies reported quality of life data. Conclusion IPAA is safe in older patients, although treating clinicians should bear in mind the increased risk of dehydration. Postoperative function is worse in older patients, but seems to level out with time and does not appear to significantly impact on overall quality of life and patient satisfaction. Assessment for suitability for RPC should not be based on chronological age in isolation. It is imperative that the correct support is given to older patients with worsened postoperative function in order to maintain patient satisfaction and adequate quality of life

Patients' inability to perform a preoperative cardiopulmonary exercise test or demonstrate an anaerobic threshold is associated with inferior outcomes after major colorectal surgery.

BACKGROUND: Surgical patients with poor functional capacity, determined by oxygen consumption at anaerobic threshold (AT) during cardiopulmonary exercise testing (CPET), experience longer hospital stays and worse short- and medium-term survival. However, previous studies excluded patients who were unable to perform a CPET or who failed to demonstrate an AT. We hypothesized that such patients are at risk of inferior outcomes after elective surgery. METHODS: All patients undergoing major colorectal surgery attempted CPET to assist in the planning of care. Patients were stratified by their test results into Fit (AT ≥ 11.0 ml O2 kg(-1) min(-1)), Unfit (AT < 11.0 ml O2 kg(-1) min(-1)), or Unable to CPET groups (failed to pedal or demonstrate an AT). For each group, we determined hospital stay and mortality. RESULTS: Between March 2009 and April 2010, 269 consecutive patients were screened, and proceeded to bowel resection. Median hospital stay was 8 days (IQR 5.1-13.4) and there were 44 deaths (16%) at 2 yr; 26 (9.7%) patients were categorized as Unable to CPET, 69 (25.7%) Unfit and 174 (64.7%) Fit. There were statistically significant differences between the three groups in hospital stay [median (IQR) 14.0 (10.5-23.8) vs 9.9 (5.5-15) vs 7.1 (4.9-10.8) days, P < 0.01] and mortality at 2 yr [11/26 (42%) vs 14/69 (20%) vs 19/174 (11%), respectively (P < 0.01)] although the differences between Unable and Unfit were not statistically different. CONCLUSIONS: Patients' inability to perform CPET is associated with inferior outcomes after major colorectal surgery. Future studies evaluating CPET in risk assessment for major surgery should report outcomes for this subgroup

A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife

Background: This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas. Methods: Patients undergoing elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy. Results: Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy. Conclusion: REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer

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

Aim: To define good and poor regression using pathology and MRI regression scales after neo-adjuvant chemotherapy for rectal cancer. Methods: A systematic review of 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, included “tumour regression”, “mrTRG”, “poor response” and “colorectal cancers”. Clinical studies using either MRI or histopathological TRG scales to define good and poor responders were included in relation to outcomes (local (LR), distant recurrence (DR), disease free (DFS), overall survival (OS)). There was no age restriction to included patients nor stage of cancer.Data was extracted by two authors independently 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 &OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant CRT was 37.7% (CI: 30.1 to 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&2 or Dworak grades 3&4; Mandard 3,4&5 and Dworak 0,1&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 & 3) was LR 1-14%, DR 3%, DFS 64-83% and OS 72-90%. Conclusions: For histopathology regression assessment Mandard1,2/Dworak3,4 should be used for good and Mandard3,4,5/Dworak0,1,2 for poor response. MRI indicates good and poor response by mrTRG1-3 and mrTRG4-5 respectively

Terahertz pulsed imaging of freshly excised human colonic tissues

We present the results from a feasibility study which measures properties in the terahertz frequency range of excised cancerous, dysplastic and healthy colonic tissues from 30 patients. We compare their absorption and refractive index spectra to identify trends which may enable different tissue types to be distinguished. In addition, we present statistical models based on variations between up to 17 parameters calculated from the reflected time and frequency domain signals of all the measured tissues. These models produce a sensitivity of 82% and a specificity of 77% in distinguishing between healthy and all diseased tissues and a sensitivity of 89% and a specificity of 71% in distinguishing between dysplastic and healthy tissues. The contrast between the tissue types was supported by histological staining studies which showed an increased vascularity in regions of increased terahertz absorption

Interobserver agreement of radiologists assessing the response of rectal cancers to preoperative chemoradiation using the MRI tumour regression grading (mrTRG)

AIM: To investigate whether the magnetic resonance imaging (MRI) tumour regression grading (mrTRG) scale can be taught effectively resulting in a clinically reasonable interobserver agreement (>0.4; moderate to near perfect agreement). MATERIALS AND METHODS: This study examines the interobserver agreement of mrTRG, between 35 radiologists and a central reviewer. Two workshops were organised for radiologists to assess regression of rectal cancers on MRI staging scans. A range of mrTRGs on 12 patient scans were used for assessment. RESULTS: Kappa agreement ranged from 0.14–0.82 with a median value of 0.57 (95% CI: 0.37–0.77) indicating good overall agreement. Eight (26%) radiologists had very good/near perfect agreement (κ>0.8). Six (19%) radiologists had good agreement (0.8≥κ>0.6) and a further 12 (39%) had moderate agreement (0.6≥κ>0.4). Five (16%) radiologists had a fair agreement (0.4≥κ>0.2) and two had poor agreement (0.2>κ). There was a tendency towards good agreement (skewness: 0.92). In 65.9% and 90% of cases the radiologists were able to correctly highlight good and poor responders, respectively. CONCLUSIONS: The assessment of the response of rectal cancers to chemoradiation therapy may be performed effectively using mrTRG. Radiologists can be taught the mrTRG scale. Even with minimal training, good agreement with the central reviewer along with effective differentiation between good and intermediate/poor responders can be achieved. Focus should be on facilitating the identification of good responders. It is predicted that with more intensive interactive case-based learning a κ>0.8 is likely to be achieved. Testing and retesting is recommended

Creatinine and myoglobin are poor predictors of anaerobic threshold in colorectal cancer and health

Aims Myoglobin is a haem protein produced in skeletal muscles. Serum concentrations of myoglobin have been proposed as a surrogate marker of muscle mass and function in both cachectic cancer patients and healthy non-cancer individuals. Creatinine, a metabolite of creatine phosphate, an energy store found in skeletal muscle, is produced at a constant rate from skeletal muscle. Urinary and plasma creatinine have been used in clinical practice as indicators of skeletal muscle mass in health and disease. Our study aimed to test the hypothesis that plasma myoglobin and creatinine concentration could accurately predict skeletal muscle mass and aerobic capacity in colorectal cancer (CRC) patients and matched healthy controls and thereby an indicative of aerobic performance. Methods We recruited 47 patients with CRC and matching number of healthy volunteers for this study. All participants had their body composition measured by dual-energy X-ray absorptiometry scan, aerobic capacity measured to anaerobic threshold (AT) by cardiopulmonary exercise testing and filled in objective questionnaires to assess the qualitative functions. This study was carried out in accordance with the Declaration of Helsinki, after approval by the local National Health Service (NHS) Research Ethics Committee. Results Age-matched groups had similar serum myoglobin and creatinine concentrations in spite of differences in their aerobic capacity. AT was significantly lower in the CRC group compared with matched controls (1.18 ± 0.44 vs. 1.41 ± 0.71 L/min; P < 0.01). AT had significant correlation with lean muscle mass (LMM) among these groups, but myoglobin and creatinine had poor correlation with LMM and AT. Conclusions Serum myoglobin is a poor predictor of muscle mass, and serum myoglobin and creatinine concentrations do not predict aerobic performance in CRC patients or healthy matched controls