Faecal immunochemical testing in symptomatic patients to prioritize investigation: diagnostic accuracy from NICE FIT Study.

BACKGROUND: This study investigated whether a quantitative faecal immunochemical test (FIT) could be used to select patients with either high- or low-risk symptoms of colorectal cancer for urgent investigation. METHODS: A double-blinded diagnostic accuracy study was conducted in 50 hospitals in England between October 2017 and December 2019. Patients were eligible for inclusion if they had been referred to secondary care with suspected colorectal cancer symptoms meeting national criteria for urgent referral and triaged to investigation with colonoscopy. RESULTS: The study included 9822 patients, of whom 7194 (73.2 per cent) had high-risk symptoms, 1994 (20.3 per cent) low-risk symptoms, and 634 (6.5 per cent) had other symptoms warranting urgent referral. In patients with high-risk symptoms, the sensitivity of FIT for colorectal cancer at cut-off values of 2 and 10 µg haemoglobin per g faeces was 97.7 (95 per cent c.i. 95.0 to 99.1) and 92.2 (88.2 to 95.2) per cent respectively, compared with 94.3 (84.3 to 98.8) and 86.8 (74.7 to 94.5) per cent in patients with low-risk symptoms at the same cut-off points. At cut-off values of 2, 10, and 150 µg/g, the positive predictive value for colorectal cancer was 8.9, 16.2, and 30.5 per cent respectively for those with high-risk symptoms, and 8.4, 16.9, and 35.5 per cent for those with low-risk symptoms. CONCLUSION: FIT safely selects patients with high or low risk symptoms of colorectal cancer for investigation.

Ex vivo specimen MRI and pathology confirm a rectosigmoid mesenteric waist at the junction of the mesorectum and mesocolon.

AIM: Continuity of the mesentery has recently been established and may provide an anatomical basis for optimal colorectal resectional surgery. Preliminary data from operative specimen measurements suggest there is a tapering in the mesentery of the distal sigmoid. A mesenteric waist in this area may be a risk factor for local recurrence of colorectal cancer. This study aimed to investigate the anatomical characteristics of the mesentery at the colorectal junction. METHOD: In this cross-sectional study, 20 patients were recruited. After planned colorectal resection, the surgical specimens were scanned in a MRI system and subsequently dissected and photographed as per national pathology guidelines. Mesenteric surface area and linear measurements were compared between MRI and pathology to establish the presence and location of a mesenteric waist. RESULTS: Specimen analysis confirmed that a narrowing in the mesenteric surface area was consistently apparent at the rectosigmoid junction. Above the anterior peritoneal reflection, the surface area and posterior distance of the mesentery of the upper rectum initially decreased before increasing as the mesentery of the sigmoid colon. These anatomical properties created the appearance of a mesenteric 'waist' at the rectosigmoid junction. Using the anterior reflection as a reference landmark, the rectosigmoid waist occurred at a mean height of 23.6 and 21.7 mm on MRI and pathology, respectively. CONCLUSION: A rectosigmoid waist occurs at the junction of the mesorectum and mesocolon, and is a mesenteric landmark for the rectum that is present on both radiology and pathology.

The diagnostic accuracy of the faecal immunochemical test for colorectal cancer in risk-stratified symptomatic patients.

INTRODUCTION: The faecal immunochemical test detects blood in the faeces, reporting faecal haemoglobin quantitatively in micrograms of haemoglobin per gram of faeces. The aim of this pilot study was to determine the feasibility of using the faecal immunochemical test as a rule-out test in symptomatic patients at low and high risk of colorectal cancer. MATERIAL AND METHODS: Between November 2016 and October 2017, consecutive symptomatic patients within a multicultural part of London were recruited to perform a faecal immunochemical test prior to colonoscopy. Analysis was performed on the HM-JACKarc analyser. RESULTS: Faecal immunochemical test samples were returned by 298 patients who underwent colonoscopy. There was no significant variation in faecal haemoglobin levels by age, sex, ethnicity or deprivation. The overall detection rate for colorectal cancer was 100% at 2 µg/g and 92% at 10 µg/g. If a faecal haemoglobin threshold for investigation of 2 µg/g (ie detectable) or 10 µg/g had been employed, the number of colonoscopies would have been reduced by 70% and 84%, respectively, in all symptomatic patients. For low-risk patients, the sensitivity of the faecal immunochemical test for colorectal cancer at both thresholds of 2 µg/g or 10 µg/g remained 100%, with the number of colonoscopies reduced by 80% and 91%, respectively. CONCLUSION: This study shows that the faecal immunochemical test is a promising technology that detected colorectal cancer in all high- or low-risk symptomatic patients in our cohort at a threshold of detectable faecal haemoglobin. Data from adequately powered cohort studies will elucidate the true diagnostic accuracy of the test and the rate and patterns of undetected colorectal cancer.

Variation in landmarks for the rectum: an MRI study.

AIM: This study aimed to assess the reliability of measurements and bony landmarks for the rectosigmoid junction on MRI. METHOD: The staging MRI scans for 100 patients were reviewed. The junction of the mesorectum and mesocolon was used to identify the rectum and sigmoid. The performance of current metric measurements or bony landmarks was then compared against the actual anatomical bowel segment. RESULTS: The mean distance of the sigmoid take-off from the anal verge was 12.6 cm (SD 1.8 cm, range 9.4-19.0 cm). At a cutoff of 12 cm, the anatomical bowel segment was found to be sigmoid colon rather than rectum in 35% of patients. At 15 and 16 cm the bowel segment was sigmoid in 84% and 96% of patients, respectively. At the sacral promontory and the third sacral segment, the bowel segment was sigmoid in 28% and 100% of patients, respectively. CONCLUSION: Current definitions of the rectum that rely on arbitrary measurements or bony landmarks will not locate the correct point of transition between the rectum and sigmoid in the majority of patients. The sigmoid take-off offers an alternative, anatomically bespoke, landmark.

CT and 3-T MRI accurately identify T3c disease in colon cancer, which strongly predicts disease-free survival.

AIM: To compare the preoperative staging accuracy of computed tomography (CT) and 3-T magnetic resonance imaging (MRI) in colon cancer, and to investigate the prognostic significance of identified risk factors. MATERIALS AND METHODS: Fifty-eight patients undergoing primary resection of their colon cancer were prospectively recruited, with 53 patients included for final analysis. Accuracy of CT and MRI were compared for two readers, using postoperative histology as the reference standard. Patients were followed-up for a median of 39 months. Risk factors were compared by modality and reader in terms of metachronous metastases and disease-free survival (DFS), stratified for adjuvant chemotherapy. RESULTS: Accuracy for the identification of T3c+ disease was non-significantly greater on MRI (75% and 79%) than CT (70% and 77%). Differences in the accuracy of MRI and CT for identification of T3+ disease (MRI 75% and 57%, CT 72% and 66%) and N+ disease (MRI 62% and 63%, CT 62% and 56%) were also non-significant. Identification of extramural venous invasion (EMVI+) disease was significantly greater on MRI (75% and 75%) than CT (79% and 54%) for one reader (p=0.029). T3c+ disease at histopathology was the only risk factor that demonstrated a significant difference in rate of metachronous metastases (odds ratio [OR] 8.6, p=0.0044) and DFS stratified for adjuvant therapy (OR=4, p=0.048). CONCLUSION: T3c or greater disease is the strongest risk factor for predicting DFS in colon cancer, and is accurately identified on imaging. T3c+ disease may therefore be the best imaging entry criteria for trials of neoadjuvant treatment.

A study of genomic instability in early preneoplastic colonic lesions.

It is difficult to explain the differential rates of progression of premalignant colonic lesions and differences in behaviour of morphologically similar lesions. Heterogeneity for microsatellite instability (MSI) and promoter methylation in driving these phenomena forward may explain this; however, no previous analysis has examined this in detail at the gland level, the smallest unit of colorectal premalignant lesions. We aimed to carry out an analysis of gland level genomic instability for MSI and promoter methylation. MSI occurred significantly more frequently (20%) in colonic glands than has previously been observed in whole colorectal polyps. Significant promoter methylation was seen in MLH1, PMS2, MLH3 and MSH3 as well as significant heterogeneity for both MSI and promoter methylation. Methylation and MSI may have a significant role in driving forward colorectal carcinogenesis, although in the case of MSI, this association is less clear as it occurs significantly more frequently than previously thought, and may simply be a passenger in the adenoma-carcinoma sequence. Promoter methylation in MLH1, MLH3, MSH3 and PMS2 was also found to be significantly associated with MSI and should be investigated further. A total of 273 colorectal glands (126 hyperplastic, 147 adenomatous) were isolated via laser capture microdissection (targeted at regions of MLH1 loss) from 93 colonic polyps and tested for MSI, and promoter methylation of the DNA mismatch repair genes MLH1, MSH2, MLH3, MSH6, PMS2, MGMT and MLH3 via methylation specific multiplex ligation-dependent probe amplification. Logistic regression modelling was then used to identify significant associations between promoter methylation and gland histological type and MSI status.

Management of complex pelvic floor disorders in a multidisciplinary pelvic floor clinic.

OBJECTIVE: To identify symptom clusters, management strategies and survey patient satisfaction in our combined multidisciplinary pelvic floor clinic (PFC). METHOD: Retrospective cohort study, patient satisfaction questionnaire. SAMPLE: Secondary and tertiary referrals with complex pelvic floor disorders. MAIN OUTCOME MEASURES: symptom clusters and treatment received; patient satisfaction. RESULTS: A total of 113 new cases over a 3-year period. There were two main symptom clusters: (i) obstructed defaecation with rectoceles (n = 55); of these, 23 had abdominal sacrocolpopexy with rectopexy, six had transvaginal rectocele repairs; and (ii) of the 33 with double incontinence, 10 had anal sphincter repairs, five had tension-free vaginal tapes and two had colposuspensions. Patient satisfaction audit: 73% found the care to be excellent/good, 12% satisfactory and 6% unsatisfactory. CONCLUSION: Combined PFCs led to a more pragmatic approach in treating patients' symptoms. Combined surgery was undertaken in one-fourth of patients and is associated with cost savings and a single recuperation period. Overall, patients rated this service very highly.