Does prehabilitation modify muscle mass in patients with rectal cancer undergoing neoadjuvant therapy? A subanalysis from the REx randomised controlled trial.

BACKGROUND: Patients with rectal cancer who present with sarcopenia (low muscle mass) are at significantly greater risk of postoperative complications and reduction in disease-free survival. We performed a subanalysis of a randomised controlled study [the REx trial; www.isrctn.com ; 62859294] to assess the potential of prehabilitation to modify muscle mass in patients having neoadjuvant chemoradiotherapy (NACRT). METHODS: Patients scheduled for NACRT, then potentially curative surgery (August 2014-March 2016) had baseline physical assessment and psoas muscle mass measurement (total psoas index using computed tomography-based measurements). Participants were randomised to either the intervention (13-17-week telephone-guided graduated walking programme) or control group (standard care). Follow-up testing was performed 1-2 weeks before surgery. RESULTS: The 44 patients had a mean age of 66.8 years (SD 9.6) and were male (64%); white (98%); American Society of Anesthesiologists class 2 (66%); co-morbid (58%); overweight (72%) (body mass index ≥ 25 kg/m2). At baseline, 14% were sarcopenic. At follow-up, 13 (65%) of patients in the prehabilitation group had increased muscle mass versus 7 (35%) that experienced a decrease. Conversely, 16 (67%) controls experienced a decrease in muscle mass and 8 (33%) showed an increase. An adjusted linear regression model estimated a mean treatment difference in Total Psoas Index of 40.2mm2/m2 (95% CI - 3.4 to 83.7) between groups in change from baseline (p = 0.07). CONCLUSIONS: Prehabilitation improved muscle mass in patients with rectal cancer who had NACRT. These results need to be explored in a larger trial to determine if the poorer short- and long-term patient outcomes associated with low muscle mass can be minimised by prehabilitation.

Lifestyle in patients at increased risk of colorectal cancer.

BACKGROUND: The present study aimed to assess modifiable risk factors in patients at high risk for colorectal cancer (CRC) and their experience of lifestyle advice. METHODS: A questionnaire study was conducted in high-risk CRC patients attending for surveillance colonoscopy. Current lifestyle behaviours [smoking, alcohol, diet (fruit and vegetables, wholegrains, red meat, processed meat), physical activity and bodyweight] related to CRC were ascertained, and experience on receiving, seeking and desire for advice was queried. RESULTS: In total, 385 study invitations were sent and 208 (54%) questionnaires were returned. The majority of participants (72%) were estimated to have a body mass index beyond the healthy range, 89% achieved a fibre score indicative of a low plant-based diet and 91% reported eating processed meat. Overall, 36% were achieving at least four recommendations and 2% were adhering to all recommendations examined. The main area in which participants reported receiving advice on was body weight (33%) and 31% reported that they had personally sought information on this topic, although the data suggest that 72% of people may benefit from such guidance. Fewer participants reported receiving (18-26%) and seeking (15-17%) dietary advice on fruits, vegetables and wholegrains. Many participants said they would find lifestyle information useful, notably in relation to body fatness (43%) and physical activity (38%). CONCLUSIONS: The development of a process for supporting lifestyle change in this patient group, comprising individuals who are already engaging in positive health practices (regular colonoscopy surveillance), could usefully be identified and tested.

Prehabilitation is feasible in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy and may minimize physical deterioration: results from the REx trial.

AIM: Rectal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT) experience physical deterioration and reductions in their quality of life. This feasibility study assessed prehabilitation (a walking intervention) before, during and after NACRT to inform a definitive multi-centred randomized clinical trial (REx trial). METHODS: Patients planned for NACRT followed by potentially curative surgery were approached (August 2014-March 2016) (www.isrctn.com; 62859294). Prior to NACRT, baseline physical and psycho-social data were recorded using validated tools. Participants were randomized to either the intervention group (exercise counselling session followed by a 13-17 week telephone-guided walking programme) or a control group (standard care). Follow-up testing was undertaken 1-2 weeks before surgery. RESULTS: Of the 296 screened patients, 78 (26%) were eligible and 48 (61%) were recruited. N = 31 (65%) were men with a mean age of 65.9 years (range 33.7-82.6). Mean intervention duration was 14 weeks with 75% adherence. n = 40 (83%) completed follow-up testing. Both groups recorded reductions in daily walking but the reduction was less in the intervention group although not statistically significant. Participants reported high satisfaction and fidelity to trial procedures. CONCLUSION: This study demonstrates that prehabilitation is feasible in rectal cancer patients undergoing NACRT. Good recruitment, adherence, retention and patient satisfaction rates support the development of a fully powered trial. The effects of the intervention on physical outcomes were promising.

The colorectal surgeon's personality may influence the rectal anastomotic decision.

AIM: Colorectal surgeons regularly make the decision to anastomose, defunction or form an end colostomy when performing rectal surgery. This study aimed to define personality traits of colorectal surgeons and explore any influence of such traits on the decision to perform a rectal anastomosis. METHOD: Fifty attendees of The Association of Coloproctology of Great Britain and Ireland 2016 Conference participated. After written consent, all underwent personality testing: alexithymia (inability to understand emotions), type of thinking process (intuitive versus rational) and personality traits (extraversion, agreeableness, openness, emotional stability, conscientiousness). Questions were answered regarding anastomotic decisions in various clinical scenarios and results analysed to reveal any influence of the surgeon's personality on anastomotic decision. RESULTS: Participants were: male (86%), consultants (84%) and based in England (68%). Alexithymia was low (4%) with 81% displaying intuitive thinking (reflex, fast). Participants scored higher in emotional stability (ability to remain calm) and conscientiousness (organized, methodical) compared with population norms. Personality traits influenced the next anastomotic decision if: surgeons had recently received criticism at a departmental audit meeting; were operating with an anaesthetist that was not their regular one; or there had been no anastomotic leaks in their patients for over 1 year. CONCLUSION: Colorectal surgeons have speciality relevant personalities that potentially influence the important decision to anastomose and could explain the variation in surgical practice across the UK. Future work should explore these findings in other countries and any link of personality traits to patient-related outcomes.

Session 3: Intra-operative radiotherapy - creating new surgical boundaries.

In patients with advanced and recurrent colorectal cancer, surgical resection with clear margins is the greatest challenge and is limited by known anatomical constraints. Preoperative or intra-operative assessment of the limits of surgical dissection may help to explore the possibility of improving resectability through either targeted external beam radiotherapy or intra-operative radiotherapy. Professor Chang reviews the evidence base and potential advantages and disadvantages of this approach, whilst the expert panel agree a consensus on the evidence for assessment and therapy of such patients.

Session 3: Beyond the boundaries of Total Mesorectal Excision - where surgeons fear to tread.

Approximately 10-15% of patients present with an advanced rectal cancer that extends beyond the conventional total mesorectal excision (TME) planes. In such cases extending the surgery to ensure resection with clear margins (R0 resection) is essential in order to achieve long-term cure. Professor Holm describes the techniques of beyond-TME exenterative surgery, the methods of patient selection and outcomes.

Session 3: Many ways to organ preserve the rectum but which is correct?

From the patient's perspective, cancer cure with full preservation of function is a crucial goal. There are many advances that have emerged which may make this possible in a greater proportion of patients without compromising oncological outcomes. Professor Tekkis reviews the options and evidence to date for 'organ preservation' and the expert panel discuss the implications for current and future patient care.

Scottish Bowel Screening Programme colonoscopy quality - scope for improvement?

AIM: The delivery of the Scottish Bowel Screening Programme (SBoSP) is rooted in the provision of a high quality, effective and participant-centred service. Safe and effective colonoscopy forms an integral part of the process. Additional accreditation as part of a multi-faceted programme for participating colonoscopists, as in England, does not exist in Scotland. This study aimed to describe the quality of colonoscopy in the SBoSP and compare this to the English national screening standards. METHODS: Data were collected from the SBoSP between 2007 and 2014. End-points for analysis were caecal intubation, cancer, polyp and adenoma detection, and complications. Overall results were compared with 2012 published English national standards for screening and outcomes from 2006 to 2009. RESULTS: During the study period 53 332 participants attended for colonoscopy. The colonoscopy completion rate was 95.6% overall. The mean cancer detection rate was 7.1%, the polyp detection rate was 45.7% and the adenoma detection rate was 35.5%. The overall complication rate was 0.47%. CONCLUSION: Colonoscopy quality in the SBoSP has exceeded the standard set for screening colonoscopy in England, despite not adopting a multi-faceted programme for screening colonoscopy. However, the overall adenoma detection rate in Scotland was 9.1% lower than that in England which has implications for colonoscopy quality and may have an impact on cancer prevention rates, a key aim of the SBoSP.

Participation in bowel screening among men attending abdominal aortic aneurysm screening.

BACKGROUND: Uptake of population-based screening for colorectal cancer in Scotland is around 55 per cent. Abdominal aortic aneurysm (AAA) screening has recently been introduced for men aged 65 years and the reported uptake is 78 per cent. The aim was to determine the impact of a brief intervention on bowel screening in men who attended AAA screening, but previously failed to complete bowel screening. METHODS: Men invited for AAA screening between September 2015 and March 2016 within NHS Tayside were included. Attendees who had not responded to their latest bowel screening invitation were seen by a colorectal cancer clinical nurse specialist. Reasons for not completing the faecal occult blood test (FOBT) were recorded; brief information on colorectal cancer screening was communicated, and participants were offered a further invitation to complete a FOBT. Those who responded positively were sent a further FOBT from the Scottish Bowel Screening Centre. Subsequent return of a completed FOBT within 6 months was recorded. RESULTS: A total of 556 men were invited for AAA screening, of whom 38·1 per cent had not completed a recent FOBT. The primary reason stated for not participating was the time taken to complete the test or forgetting it (35·1 per cent). Other reasons included: lack of motivation (23·4 per cent), confusion regarding the aim of screening (16·2 per cent), disgust (19·8 per cent), fear (6·3 per cent) and other health problems (9·9 per cent). Following discussion, 81·1 per cent agreed to complete the FOBT and 49 per cent subsequently returned the test. CONCLUSION: A substantial proportion of previous bowel screening non-responders subsequently returned a completed FOBT following a brief intervention with a nurse specialist. Attendance at non-bowel screening appointments may provide a valuable opportunity to improve bowel screening uptake.

Back-to-back colon capsule endoscopy and optical colonoscopy in colorectal cancer screening individuals.

AIM: The aim was to determine the polyp detection rate and per-patient sensitivity for polyps > 9 mm of colon capsule endoscopy (CCE) compared with colonoscopy as well as the diagnostic accuracy of CCE. METHOD: Individuals who had a positive immunochemical faecal occult blood test during screening had investigator blinded CCE and colonoscopy. Participants underwent repeat endoscopy if significant lesions detected by CCE were considered to have been missed by colonoscopy. RESULTS: There were 253 participants. The polyp detection rate was significantly higher in CCE compared with colonoscopy (P = 0.02). The per-patient sensitivity for > 9 mm polyps for CCE and colonoscopy was 87% (95% CI: 83-91%) and 88% (95% CI: 84-92%) respectively. In participants with complete CCE and colonoscopy examinations (N = 126), per-patient sensitivity of > 9 mm polyps in CCE (97%; 95% CI: 94-100%) was superior to colonoscopy (89%; 95% CI: 84-94%). A complete capsule endoscopy examination (N = 134) could detect patients with intermediate or greater risk (according to the European guidelines) with an accuracy, sensitivity, specificity and positivity rate of 79%, 93%, 69% and 58% respectively, using a cut-off of at least one polyp > 10 mm or more than two polyps. CONCLUSION: CCE is superior to colonoscopy in polyp detection rate and per-patient sensitivity to > 9 mm polyps, but only in complete CCE examinations. The rate of incomplete CCE examinations must be improved.

The impact of social deprivation on the response to a randomised controlled trial of a weight management intervention (BeWEL) for people at increased risk of colorectal cancer.

BACKGROUND: Although 45% of colorectal cancer (CRC) cases may be avoidable through appropriate lifestyle and weight management, health promotion interventions run the risk of widening health inequalities. The BeWEL randomised controlled trial assessed the impact of a diet and activity programme in overweight adults who were diagnosed with a colorectal adenoma, demonstrating a significantly greater weight loss at 12 months in intervention participants than in controls. The present study aimed to compare BeWEL intervention outcomes by participant deprivation status. METHODS: The intervention group of the BeWEL trial (n = 163) was classified by the Scottish Index of Multiple Deprivation (SIMD) quintiles into 'more deprived' (SIMD 1-2, n = 58) and 'less deprived' (SIMD 3-5, n = 105). Socio-economic and lifestyle variables were compared at baseline to identify potential challenges to intervention adherence in the more deprived. Between group differences at 12 months in primary outcome (change in body weight) and secondary outcomes (cardiovascular risk factors, diet, physical activity, knowledge of CRC risk and psychosocial variables) were assessed by deprivation status. RESULTS: At baseline, education (P = 0.001), income (P < 0.001), spending on physical activity (P = 0.003) and success at previous weight loss attempts (P = 0.007) were significantly lower in the most deprived. At 12 months, no between group differences by deprivation status were detected for changes in primary and main secondary outcomes. CONCLUSIONS: Despite potential barriers faced by the more deprived participants, primary and most secondary outcomes were comparable between groups, indicating that this intervention is unlikely to worsen health inequalities and is equally effective across socio-economic groups.

Developing a national colorectal educational agenda: a survey of the Association of Coloproctology of Great Britain and Ireland.

AIM: In order to develop its education agenda, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) sought the opinion of its members on current coloproctology training needs. The aims of this study were to canvass multidisciplinary needs and explore the perceived gaps and barriers to meeting them. METHOD: A learner-needs analysis was performed between July 2015 and October 2016. A bespoke electronic survey was sent to 1453 colorectal healthcare professionals [ACPGBI membership (1173), colorectal nurse specialists and allied health professionals (NAHPs) (261) and regional chapter-leads (19)] seeking their needs, experiences and barriers to training across the coloproctology disciplines. RESULTS: In all, 390 responses were received [26.8% overall; 180 consultants/trainees (15%); 196 NAHPs (75%); 14 (74%) chapter-leads]. Lack of funding and difficulties in obtaining study leave were the most frequently reported barriers to course and conference attendance. Transanal total mesorectal excision and laparoscopic training were the top educational needs for consultants and trainees respectively. 79% of NAHP respondents reported education gaps on a broad range of clinical and non-clinical topics. NAHPs lacked information on relevant training opportunities and 27% felt available courses were insufficient to meet their educational needs. Wide heterogeneity in ACPGBI chapter composition and activity was reported. All groups felt the ACPGBI should increase the number of courses offered with coloproctology knowledge updates commonly requested. CONCLUSION: A series of training needs across the coloproctology disciplines have been identified. These will underpin the development of the educational agenda for the ACPGBI.

Laparoscopic-assisted colonoscopy: results and follow-up endoscopic success.

AIM: Incomplete colonoscopy occurs in 8-10% of attempted examinations. An incomplete colonoscopy is usually followed by radiological evaluation of the large bowel to complete the colonic assessment. Patients then found to have polyps of > 1 cm represent a significant management dilemma. This study describes our experience using laparoscopy to facilitate complete colonoscopy and polypectomy in patients with fixed angulation and the success of subsequent colonoscopies. METHOD: All patients from 2008 to 2012 with an incomplete colonoscopy because of fixed angulation and with polyps detected by subsequent imaging underwent standard laparoscopy with colonic mobilization by division of adhesions to facilitate direct vision. Completion of colonoscopy and polypectomy, intra-operative complications, postoperative morbidity and successful standard follow-up colonoscopy were studied. RESULTS: Twelve patients underwent the procedure. Complete colonoscopy to caecum was successful in all, with a median of 2 (range 1-5) polyps per patient and a mean polyp size of 22 mm. One iatrogenic enterotomy was repaired immediately, with no sequelae. Ten patients have since undergone colonoscopy under sedation, with complete colonic evaluation possible in nine of the patients. CONCLUSION: Laparoscopic-assisted colonoscopy allows safe polypectomy in patients with incomplete colonoscopy, without the need for segmental resection. This less-invasive procedure yields recovery times similar to those of colonoscopy alone, avoiding the morbidity of a segmental resection with the added benefit of successful routine colonoscopy in the future.

A multistate framework for the analysis of subsequent injury in sport (M-FASIS).

Physical activity is beneficial for many aspects of health but is associated with a risk of injury. Studies that assess causal risk factors of injury and reinjury provide valuable information to help develop and improve injury prevention programs. However, the underlying assumptions of analytical approaches often used to estimate causal factors in injury and subsequent injury research are often violated. This means that ineffective or even harmful interventions could be proposed because the underlying analyses produced unreliable or invalid causal effect estimates. We describe an adapted version of the multistate framework [multistate framework for the analysis of subsequent injury in sport (M-FASIS)] that makes investigator choices more transparent with respect to outcome and healing time. In addition, M-FASIS incorporates all previous sport injury analytical frameworks and accounts for injuries or conditions that heal or do not heal to 100%, acute and overuse injuries, illnesses, and competing event outcomes.

MicroRNA-224 is associated with colorectal cancer progression and response to 5-fluorouracil-based chemotherapy by KRAS-dependent and -independent mechanisms.

BACKGROUND: Colorectal cancers arise from benign adenomas, although not all adenomas progress to cancer and there are marked interpatient differences in disease progression. We have previously associated KRAS mutations with disease progression and reduced survival in colorectal cancer patients. METHODS: We used TaqMan low-density array (TLDA) qRT-PCR analysis to identify miRNAs differentially expressed in normal colorectal mucosa, adenomas and cancers and in isogeneic KRAS WT and mutant HCT116 cells, and used a variety of phenotypic assays to assess the influence of miRNA expression on KRAS activity, chemosensitivity, proliferation and invasion. RESULTS: MicroRNA-224 was differentially expressed in dysplastic colorectal disease and in isogeneic KRAS WT and mutant HCT116 cells. Antagomir-mediated miR-224 silencing in HCT116 KRAS WT cells phenocopied KRAS mutation, increased KRAS activity and ERK and AKT phosphorylation. 5-FU chemosensitivity was significantly increased in miR-224 knockdown cells, and in NIH3T3 cells expressing KRAS and BRAF mutant proteins. Bioinformatics analysis of predicted miR-224 target genes predicted altered cell proliferation, invasion and epithelial-mesenchymal transition (EMT) phenotypes that were experimentally confirmed in miR-224 knockdown cells. CONCLUSIONS: We describe a novel mechanism of KRAS regulation, and highlight the clinical utility of colorectal cancer-specific miRNAs as disease progression or clinical response biomarkers.

Systematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks.

BACKGROUND: Anastomotic leak (AL) represents a dreaded complication following colorectal surgery, with a prevalence of 1-19 per cent. There remains a lack of consensus regarding factors that may predispose to AL and the relative risks associated with them. The objective was to perform a systematic review of the literature, focusing on the role of preoperative, intraoperative and postoperative factors in the development of colorectal ALs. METHODS: A systematic review was performed to identify adjustable and non-adjustable preoperative, intraoperative and postoperative factors in the pathogenesis of AL. Additionally, a severity grading system was proposed to guide treatment. RESULTS: Of 1707 papers screened, 451 fulfilled the criteria for inclusion in the review. Significant preoperative risk factors were: male sex, American Society of Anesthesiologists fitness grade above II, renal disease, co-morbidity and history of radiotherapy. Tumour-related factors were: distal site, size larger than 3 cm, advanced stage, emergency surgery and metastatic disease. Adjustable risk factors were: smoking, obesity, poor nutrition, alcohol excess, immunosuppressants and bevacizumab. Intraoperative risk factors were: blood loss/transfusion and duration of surgery more than 4 h. Stomas lessen the consequences but not the prevalence of AL. In the postoperative period, CT is the most commonly used imaging tool, with or without rectal contrast, and a C-reactive protein level exceeding 150 mg/l on day 3-5 is the most sensitive biochemical marker. A five-level classification system for AL severity and appropriate management is presented. CONCLUSION: Specific risk factors and their potential correction or indications for stoma were identified. An AL severity score is proposed to aid clinical decision-making.