Type of publication:
Conference abstract

Author(s):
*Lacy-Colson J.

Citation:
Colorectal Disease. Conference: Association of Coloproctology of Great Britain and Ireland Annual Meeting. Edinburgh United Kingdom. 24(Supplement 2) (pp 15), 2022. Date of Publication: September 2022.

Abstract:
Background: The Colorectal 2-week wait (2WW) pathway is overwhelmed. qFiT has been added to the pathway, however cancer detection rate remains low ~5%. Using a novel rectal mucus sampling device (OricolTM) we hypothesized that shed genetic material could be retrieved from rectal mucus using OricolTM, potentially forming an accurate triage tool for colonoscopy or other investigation (Oricol EGI-02 Study). Method(s): The OricolTM device was used in symptomatic patients recruited from 4 NHS Trusts. DNA from FFPE-histology blocks was compared to the pre-operative OricolTM rectal mucus specimen. Using targeted next generation sequencing (NGS) incorporating error suppression technology, including unique molecular indexes (UMI's) and dual indexes (UDI's) for removal of PCR/sequencing errors/index hopping events, we assessed the single nucleotide polymorphisms (SNPs) present in 50 known CRC genes across both samples. Current recruitment to the Oricol-EGI- 02 Study is 586/600. 35 paired samples and 35 Oricol samples from normal 2WW colonoscopies were evaluated. Result(s): There were no statistical differences between tumour associated SNP burden in the FFPE-blocks and the rectal mucus sample from CRC patients. Tumour associated SNP burden in the paired cancer samples was significantly higher compared to the normal group (p < 0.001). Identical SNPs were identified in both tumour and paired Oricol samples. Conclusion(s): This result confirms the hypothesis that shedding of DNA from colorectal cancers (caecum to rectum) can be detected in rectal mucus using OricolTM. Sampling rectal mucus could be used to accurately detect CRC in unprepared patients, dramatically reducing the number of normal colonoscopies which currently overwhelm the 2WW pathway.

Link to full-text [OpenAthens account required. p.10]

Type of publication:
Conference abstract

Author(s):
*Chang J.; *Rajalingam V.; *Dowdeswell M.; *Ball W.

Citation:
Colorectal Disease. Conference: Association of Coloproctology of Great Britain and Ireland Annual Meeting. Edinburgh United Kingdom. 24(Supplement 2) (pp 77), 2022. Date of Publication: September 2022.

Abstract:
Purpose: Diverting loop-ostomies are sometimes formed in patients undergoing resection for rectal cancer with primary anastomosis. Timing to reversal is commonly reported between 3-6 months of original surgery, with longstanding issues of delays secondary to low-surgical prioritisation. Our retrospective study over a 5-year period aims to understand the effect on timing to reversal of the COVID-19 pandemic. Method(s): All patients undergoing resection for rectal cancer were identified from the Hospital Episode Statistics data between 01.01.2018 and 01.07.2021. Data was then cross-referenced with patients undergoing reversal surgery. Demographics, time to surgery, length of stay and post-operative morbidity data were collected. <br/>Result(s): There were 262 anterior resections performed. 192 patients had resection with primary anastomosis (PA): 85 had formation of loop ileostomy, 23 formation of loop colostomy. Results before March 2020: 65 resections with PA and ileostomy. 34 (52.3%) reversed with median time to reversal of 266 days, (range 98-1015). 16 resections with PA and colostomy. 7 reversed (44%), median time to reversal 476 days (range 104-768). Results after March 2020: 20 resections with PA and loop-ileostomy. 3 have been reversed (15%), with median time to reversal of 211 days, (range 103-449). 7 resections with PA and colostomy, none reversed. Showing reduction in overall stoma-reversal in the post pandemic period (p = 0.000297). Conclusion(s): We will experience ongoing conflicts with prioritisation of caseloads as the ongoing effects of COVID continue. This is the time for novel solutions to a building crisis, such as ring-fenced lists or same-day surgery with ambulatory follow-up.

Link to full-text [p. 34, NHS OpenAthens account required]

Type of publication:
Conference abstract

Author(s):
*Rajalingam V.; *Chang J.; *Dowdeswell M.; *McCloud J.; *Cheetham M.

Citation:
Colorectal Disease. Conference: Association of Coloproctology of Great Britain and Ireland Annual Meeting. Edinburgh United Kingdom. 24(Supplement 2) (pp 77), 2022. Date of Publication: September 2022.

Abstract:
Purpose: For decades there has been very little change in practice in the surgical management of perforated diverticulitis. Reluctance to risk anastomotic leak persists despite increasing recognition that primary anastomosis (PA) should be considered in selected patients as an alternative to Hartmanns Procedure (HP). We retrospectively studied our outcomes for patients undergoing resectional surgery for diverticulitis. Method(s): All patients undergoing emergency resectional surgery for perforated diverticulitis between March 2015 and Jan 2021 were identified from the Hospital Episode Statistics (HES) data. Demographics were collected and the patient groups were case matched for age and Charleson Comorbidity Index (CCI), Computed Tomography (CT) appearance and intraoperative contamination data. Result(s): 105 patients were included. 15 patients had PA (without diversion) and 90 HP. In the PA cohort were 10 males, median age 52 (range 27-76). There were no anastomotic leaks. 30-day morbidities were superficial wound dehiscence (1) and early incisional hernia (1). Median post-operative stay was 9 days (range 5-25). HP control group (age below 76, CCI 10 and below, Hinchey 1-3). 58 patients, 26 males, median age 60.5 (range 30-76). Median post-operative stay was 10.5 days (range 5-227). 2 patients required re-operation. 5 patients developed wound infections. At the time of the study 18 patients have undergone reversal, 6 are on waiting-list. There was a single 30-day mortality (post-discharge). Conclusion(s): PA in selected patients is not only safe, but has lower morbidity than HP. We should be challenging the status quo and offering our patients appropriate surgery on an individualised basis.

Link to full-text [p. 56, NHS OpenAthens account required]

Type of publication:
Journal article

Author(s):
Humphrey H.N.; Diodato A.; Isner J.-C.; Walker E.; *Lacy-Colson J.; Nedjai B.; Daniels I.R.; McDermott F.D.; Walker E.T.; Battersby N.J.; Sisodia H.; Rottenburg H.; Cunningham C.; Bird S.; Jones G.A.R.; Wise D.; Spencer S.J.;

Citation:
Techniques in Coloproctology. 27(3):227-235, 2023 Mar.

Abstract:
Background: The ORI-EGI-02 study was designed to test the hypothesis that rectal mucus collected using a novel rectal sampling device (OriColTM), contains sufficient human deoxyribonucleic acid (DNA) of the required quality for Next Generation Sequencing (NGS), for colorectal disease genetic signature discovery. Method(s): Using National Institute for Health and Care Research methodology, an internal pilot study was performed in January 2020-May 2021, at four sites in the United Kingdom, to assess the process of recruitment, consent, specimen acquisition and viability for analysis. Following an OriCol^TM test, the sample was stabilized with a buffer solution to preserve the material, which was posted to the laboratory. Samples were processed using QIAamp DNA Blood Midi kit to extract DNA and Quant-iT^TM PicoGreen dsDNA Reagent to quantify the retrieved DNA. DNA integrity was measured by Agilent TapeStation system. 25 ng of human amplifiable DNA was prepared for Next Generation Sequencing (NGS), which was performed on an Illumina NextSeq550 sequencer using the 300-cycle high output kit v2.5.
Result(s): This study assessed the first 300 patients enrolled to the ORI-EGI-02 Study (n = 800). 290/300 (96.67%) were eligible to undergo OriCol^TM sampling procedure and 285/290 (98.27%) had a successful OriCol^TM sample taken. After transportation, extraction and quantification of DNA, 96.20% (279/290) of the samples had NGS successfully performed for bioinformatic analysis. Conclusion(s): Our internal pilot study demonstrated that the OriCol^TM sampling device can capture rectal mucus from unprepared bowel in subjects who could undergo a digital rectal examination. The technique could be applied irrespective of age, frailty, or co-morbidity. Completion of the study to 800 patients and analysis of NGS data for colorectal cancer mutations will now proceed.

Link to full-text [NHS OpenAthens account required]

Altmetrics:

Type of publication:
Conference abstract

Author(s):
Forsyth K.; *Bhandal H.; Macfarlane M.; Gray C.; Hannah G.; Parkes G.

Citation:
Gut. Conference: Annual Meeting of the British Society of Gastroenterology, BSG 2022. Birmingham United Kingdom. 71(Supplement 1) (pp A47), 2022. Date of Publication: June 2022

Abstract:
Introduction We have previously shown UK South Asians (SA) with IBD are prescribed TNF antagonists earlier in disease course in comparison with white British (WB) patients, but are more likely to stop due to treatment failure (Gadhok 2020). However, it is currently unknown whether there is a similar variation in response to Tofacitinib, a non-selective JAK inhibitor. We aim to determine whether persistence to tofacitinib varies with ethnicity and evaluate real world efficacy in an inner-city tertiary referral centre. Methods Patients prescribed Tofacitinib since 2019 were identified from electronic prescribing records. The following data was collected: ethnicity (as per UK standard coding), disease history including Montreal classification of disease extent, prior advanced therapies, persistence on therapy, indication for cessation, side effects, and endoscopic and biochemical markers of disease activity. Results 30 adults with UC were prescribed tofacitinib, with a median duration of follow up of 833 days (n=31). 11 patients were female, and ethnicity was as follows: SA:11: Black:1:WB:12:Other/unstated:7. The median failure free survival was 447 days, with no significant variation associated with number of prior advanced therapies (1 prior biologic, 303.5 days (n=12) vs >1 prior biologic, 715 days (n=19) p=0.28). Comparison between characteristics and response to treatment of South Asian and White British patients, presented in table 1: There was no difference between median failure free survival of SA and WB patients (304 days vs 447 days, p=0.28). There was a trend towards lower primary non-response in SA patients, with fewer stopping treatment by 12 weeks, although this was not statistically significant (9.09% vs 33.33% p=0.17). No difference in disease duration at first prescription of tofacitinib between SA and WB patients was found (78.75 months vs 86.80 months p=0.78). 2 patients stopped treatment due to side effects, with 1 patient (SA) stopping due to MACE. Conclusion In contrast to our previous work on TNF antagonists, British SA patients prescribed tofacitinib for UC had failure free survival comparable with WB patients, with a trend towards fewer primary non responders. Although limited by sample size, these findings are reassuring given that SA patients are underrepresented in trials of novel therapies in IBD and warrants a larger study.

Link to full-text [NHS OpenAthens account required]

Type of publication:
Conference abstract

Author(s):
Kumar A.; Galbraith N.; Al-Hassi H.; Jain M.; *Butterworth J.; Steed H.; McLaughlin J.; Brookes M.

Citation:
Gut. Conference: Annual Meeting of the British Society of Gastroenterology, BSG 2022. Birmingham United Kingdom. 71(Supplement 1) (pp A156), 2022. Date of Publication: June 2022

Abstract:
Background Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea and up to 30% of patients can be misdiagnosed as irritable bowel syndrome. Type 1 BAD is secondary to ileal resection or inflammation; type 2 is idiopathic; and type 3 is secondary to other intestinal conditions such as cholecystectomy. BAD can be severely debilitating and negatively affect patients' quality of life (QoL). We carried out a multicentre prospective study exploring QoL outcomes in patients with BAD before and after treatment with colesevelam. Methods Patients with or without BAD (defined by a 23- seleno-25-homotaurocholic acid (SeHCAT) retention < 19%) were recruited into four groups: 1) SeHCAT normal control group (CG), 2) idiopathic (BAD), BAD secondary to 3) postcholecystectomy (PC) and 4) post-terminal ileal resection for Crohn's disease (CD). Patients in groups 2-4 were treated with colesevelam and dosing was titrated to symptomatic response. Patients were reviewed at 4- and 8-weekly intervals and QoL evaluated by EQ-5D-3L, SF-36, IBDQ-32 (where relevant). Clinical response was defined as patients who had improved bowel frequency by >50% or <3 bowel movements per day. Results 47 patients (BAD=24, PC=12, CD=11) completed QoL questionnaires before and after treatment and 30 CG patients completed a baseline questionnaire. The CD cohort had improved IBDQ-32 mean scores after treatment (134.6 vs 158.4, p=0.007). The BAD and CD cohort showed improved mean scores with treatment in all components of the SF-36 and EQ-5D-3L, whilst the PC cohort showed a general decline in mean scores after treatment. The CG cohort generally had higher baseline scores than the other three groups. 55% of patients clinically responded to treatment (41.7% BAD, 58.3% PC, 81.8% CD). Correlations between those deemed as responders with improvements on the IBDQ-32, SF-36 and EQ-5D-3L dimensions were not statistically significant. Conclusion Our results demonstrate improved QoL in the BAD and CD cohort with treatment. Further larger studies are recommended specifically investigating the PC cohort and whether patients may improve with newer treatments such as FXR agonists.

Link to full-text [NHS OpenAthens account required]

Type of publication:
Conference abstract

Author(s):
Kumar A.; Al-Hassi H.; Jain M.; Ford C.; Gama R.; Steed H.; *Butterworth J.; McLaughlin J.; Galbraith N.; Brookes M.; Hughes L.;

Citation:
Gut. Conference: Annual Meeting of the British Society of Gastroenterology, BSG 2022. Birmingham United Kingdom. 71(Supplement 1) (pp A157), 2022. Date of Publication: June 2022.

Abstract:
Introduction BAD is a common cause of chronic diarrhoea, affecting 1% of the general population. Type 1 is secondary to ileal resection or inflammation; type 2 is idiopathic; and type 3 is a result of other intestinal conditions such as cholecystectomy. Although the UK gold standard diagnostic test for BAD is the 75selenium-homotaurocholic acid (SeHCAT) scan, this is not widely available. This study examines the validity of measuring faecal bile acids (FBA) in a single stool sample as a diagnostic tool for bile acid diarrhoea (BAD) by direct comparison to the SeHCAT. Methods Patients with chronic diarrhoea investigated for BAD with a SeHCAT scan were prospectively recruited to the study. Patients provided random stool samples to measure FBA, using an enzyme-linked immunosorbent assay. Patients were characterised into four groups: SeHCAT negative control group (CG), post-cholecystectomy (PC), idiopathic BAD and post-terminal ileal resection Crohn's disease (CD). SeHCAT retention of <5%, 5-10%, 10-15% and >15% were considered to be severe BAD, moderate, mild and normal, respectively. Results 108 patients had a stool with a comparative SeHCAT result. FBA concentrations (umol/g) and interquartile ranges in patients in CG (2.6; 1.6-4.1), PC (4.0; 2.4-6.6) and BAD (3.6; 1.9-7.2) were similar, but all were significantly lower (p<0.001) compared to patients with CD (12.5; 10.2-16.1). FBA concentrations in patients with SeHCAT retention of <5% (8.6; 4.3-15.4) were significantly higher (p<0.005) than those with a SeHCAT retention >15% (2.6; 1.5-4.2). Using <=15% SeHCAT retention as diagnostic for BAD, the sensitivity and specificity with FBA cut-off of 1.6umol/g were 89% and 26% respectively. Conclusion This pilot study demonstrated that a single random stool sample may have potential use in diagnosing severe BAD or BAD in CD patients. Larger studies are needed to confirm the potential efficacy of a single, random FBA test to accurately diagnose BAD in the absence of SeHCAT testing.

Link to full-text [NHS OpenAthens account required]