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.

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.

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.

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.

Colorectal adenomas and diabetes: implications for disease prevention.

AIM: This study assessed the baseline type II diabetes mellitus (T2DM) risk status among overweight patients with screen-detected colorectal adenomas and explored the implications of the findings for preventative practice. METHOD: Participants aged between 50 and 74 years (73% of whom were men) were recruited from four Scottish health boards and assessed for diabetes risk. Participants were categorized as at 'high' diabetes risk if glycated haemoglobin (HbA1c) was between 6.0 and 6.4% or fasting plasma glucose (FPG) was between 5.5 and 6.9 mmol/l and as potentially undiagnosed T2DM when HbA1c ≥ 6.5% or FPG ≥ 7 mmol/l. Secondary outcome measures included anthropometric measurements, blood pressure and the plasma lipid profile. The tests were repeated at 12 months and diabetes risk categories were reassessed following intervention procedures. RESULTS: Forty-seven (14.3%) of the 329 participants had a preexisting diagnosis of T2DM. Of the remainder with complete biochemistry results (n = 250), 19 (7.6%) were classified as having potentially undiagnosed T2DM and 125 (50.0%) as being at high risk of developing diabetes. More than a quarter of participants in all categories had raised waist circumference, hypertension and plasma lipids, indicative of raised cardiovascular risk. At 12 months' follow-up, the diabetes risk category diminished in 20% of the intervention group vs 11% in the controls [OR 2.26 (95% CI 1.03-4.96)]. CONCLUSION: Our results suggest that a diagnosis of adenoma in overweight patients provides a health service opportunity for diabetes assessment, prevention and management in a high-risk population at a potentially teachable moment.

Malignancy within a Tail Gut Cyst: A Case of Retrorectal Carcinoid Tumour.

Purpose. Tailgut cysts with malignant transformation are rare entities. We discuss the diagnostic strategy and treatment of a malignancy within a tailgut cyst. Methods. In this study we report on the case of a 61-year-old man with a malignant neuroendocrine tumour arising within a tailgut cyst and an overview of the literature emphasising the histopathological characteristics and differential diagnosis. Results. Our patient presented with lower back pain, rectal pain, and increased urgency of defecation. MRI scan and CT-guided biopsy on histological analysis revealed a diagnosis of carcinoid tumour of the presacral space. The patient subsequently underwent an abdominoperineal excision of the rectum. Conclusions. This case highlights the importance of tailgut cysts as a differential diagnosis of presacral masses. It is a rare congenital lesion developing from remnants of the embryonic postanal gut and is predominantly benign in nature. Approximately half of cases remain asymptomatic; therefore, diagnosis is often delayed. Magnetic resonance imaging is the investigation of choice and an awareness of the possibility of malignant potential is critical to avoiding missed diagnosis and subsequent morbidity. Complete surgical excision allows accurate diagnosis, confirmation of oncological clearance, and prevention of mortality.

Impact of faecal occult blood test screening on emergency admissions and short-term outcomes for colorectal cancer.

BACKGROUND: Small studies have examined the effect of faecal occult blood test (FOBT) screening on the proportion of hospital admissions for colorectal cancer (CRC) classed as an emergency. This study aimed to examine this and short-term outcomes in persons invited for screening compared with a control group not invited. METHODS: The invited group comprised all individuals invited between 1 April 2000 and 31 July 2007 in the Scottish arm of the UK demonstration pilot of FOBT, and subsequently diagnosed with CRC aged 50-72 years between 1 May 2000 and 31 July 2009. The controls comprised all remaining individuals in Scotland not invited for FOBT but diagnosed with CRC aged 50-72 years in the same period. RESULTS: There were 2981 people diagnosed with CRC in the group invited for screening (58·3 per cent participated) and 9842 in the control group. Multivariable regression adjusted for sex, age, deprivation, co-morbidities, tumour site and Dukes' stage showed no difference between the groups for emergency admissions (odds ratio (OR) 0·89, 95 per cent confidence interval (c.i.) 0·77 to 1·02; P = 0·084) or length of hospital stay (LOS) (ß coefficient -1·02 (95 per cent c.i. -1·05 to 1·01) days; P = 0·226). Comparing participants with controls, there were fewer emergency admissions (OR 0·59, 0·49 to 0·71; P < 0·001) and shorter LOS (ß coefficient -1·06 (-1·10 to -1·02) days; P = 0·001). Short-term mortality was lower in the screened than the non-screened population (1·1 versus 2·8 per cent; P = 0·001). CONCLUSION: People who participated in FOBT screening had fewer emergency admissions and a shorter LOS. Deprivation was associated negatively with participation, but the impact of FOBT participation on emergency admissions was independent of deprivation level. The reduction in LOS has potential to reduce financial costs.

Patterns of uptake in a biennial faecal occult blood test screening programme for colorectal cancer.

AIM: The patterns of response in faecal occult blood test (FOBT) screening were studied. METHOD: A total of 251,578 people invited three times for faecal occult blood testing were categorized according to how they responded to the invitations, as follows: YNN, NYN, NNY, NYY, YNY, YYN, YYY or NNN (Y = response; N = no response). RESULTS: Overall, 163,038 (64.8%) responded at least once, and of those the biggest category was YYY (98,494, 60.4%). Of 1927 cancers diagnosed in the age group eligible for screening, there were 405 screen-detected cancers, 529 interval cancers and 993 cancers arising in people who had not been screened for over 2 years (i.e. falling outside the interval cancer category). In the YYY group, 79 screen-detected cancers would have been missed had the members of this group responded YNN and 65 had they responded YYN. In the YYN group, 104 screening cancers would have been missed if they had followed the YNN pattern. In most cases, the screen-detected cancers were diagnosed at the last invitation accepted, indicating that, after a diagnosis of cancer, further screening invitations were rarely accepted. Accordingly, the numbers of screen-detected and interval cancers were adjusted for likely pattern of response according to the proportion of the whole population falling into each pattern. With this adjustment, 40.9% of the cancers in the YYY group were screen detected compared with 29.3% in the YYN group and 20.7% in the YNN group (P < 0.001). Among those who responded once, twice and three times, the stage distribution of screen-detected cancers was similar, indicating that the prognosis of screen-detected cancer is unlikely to be poorer if not detected at the first screen. CONCLUSION: This study is the first to examine patterns of response to screening invitations and confirms the importance to individuals of continuing to accept repeated screening invitations.