Gastroenterology

A Pilot Study on the Effect of Colesevelam on the Microbiome in Primary Terminal Ileal Resected Crohn's Disease (2023)

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Type of publication:
Conference abstract

Author(s):
Kumar A.; Quraishi M.N.; Al-Hassi H.O.; Elasrag M.; Segal J.P.; Jain M.; Steed H.; *Butterworth J.; Farmer A.; McLaughlin J.; Beggs A.; Brookes M.

Citation:
Journal of Crohn's and Colitis. Conference: 18th Congress of European Crohn's and Colitis Organisation, ECCO 2023. Copenhagen Denmark. 17(Supplement 1) (pp i532), 2023. Date of Publication: February 2023

Abstract:
Background: Surgery plays a pivotal role in ileal Crohn's disease despite the risk of endoscopic recurrence following an ileocaecal resection greater than 65% within 12 months of surgery. More than 90% of Crohn's patients have a concomitant diagnosis of bile acid diarrhoea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in post-operative Crohn's patients with bile acid diarrhoea can alter the microbiome and prevent disease recurrence. Method(s): Post-operative Crohn's patients with symptoms of diarrhoea underwent 75SeHCAT testing for bile acid diarrhoea. If positive (75SeHCAT < 15%), patients were treated with colesevelam and stool samples were collected at 4-weeks, 8-weeks and 6-12 months posttreatment. If negative (75SeHCAT > 15%), treatment was not given and were reviewed in clinic as per local guidelines. Patients underwent a 6-12 months post-operative colonoscopy where mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeerts score < i2 and disease recurrence 3 i2. Faecal and mucosal 16S ribosomal RNA gene analysis was undertaken to assess a/b-diversity and microbial composition. Result(s): A total of 44 faecal samples and 44 mucosal biopsies were sequenced from 14 patients. 1/10 patients on colesevelam and 2/4 patients not on colesevelam demonstrated disease recurrence. There was no significant difference in a/b-diversity pre- and post-treatment. Pre-treatment, the three most abundant bacterial classes in all patients were Bacteroidia, Clostridia and Gammaproteobacteria (Figure 1). Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the two patients not given colesevelam, 1/2 (50%) showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria. Conclusion(s): This small pilot study demonstrated that patients who were given colesevelam, a bile acid sequestrant, were more likely to be in disease remission at their 6-12 months colonoscopy review. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in post-operative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance.

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Development and validation of a multivariable risk factor questionnaire to detect oesophageal cancer in 2-week wait patients (2023)

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Type of publication:
Journal article

Author(s):
Ho KMA; Rosenfeld A; Hogan Á; McBain H; Duku M; Wolfson PB; Wilson A; Cheung SM; Hennelly L; Macabodbod L; Graham DG; Sehgal V; Banerjee A; Lovat LB; SPIT Study Group Collaborators,. Included *Butterworth, J and *Button, H from Shrewsbury and Telford Hospital Trust as investigators

Citation:
Clinics and Research in Hepatology and Gastroenterology, 2023 Mar; Vol. 47 (3), pp. 102087

Abstract:
Introduction: Oesophageal cancer is associated with poor health outcomes. Upper GI (UGI) endoscopy is the gold standard for diagnosis but is associated with patient discomfort and low yield for cancer. We used a machine learning approach to create a model which predicted oesophageal cancer based on questionnaire responses. Methods: We used data from 2 separate prospective cross-sectional studies: the Saliva to Predict risk of disease using Transcriptomics and epigenetics (SPIT) study and predicting Risk of disease using detailed Questionnaires (RISQ) study. We recruited patients from National Health Service (NHS) suspected cancer pathways as well as patients with known cancer. We identified patient characteristics and questionnaire responses which were most associated with the development of oesophageal cancer. Using the SPIT dataset, we trained seven different machine learning models, selecting the best area under the receiver operator curve (AUC) to create our final model. We further applied a cost function to maximise cancer detection. We then independently validated the model using the RISQ dataset. Results: 807 patients were included in model training and testing, split in a 70:30 ratio. 294 patients were included in model validation. The best model during training was regularised logistic regression using 17 features (median AUC: 0.81, interquartile range (IQR): 0.69-0.85). For testing and validation datasets, the model achieved an AUC of 0.71 (95% CI: 0.61-0.81) and 0.92 (95% CI: 0.88-0.96) respectively. At a set cut off, our model achieved a sensitivity of 97.6% and specificity of 59.1%. We additionally piloted the model in 12 patients with gastric cancer; 9/12 (75%) of patients were correctly classified. Conclusions: We have developed and validated a risk stratification tool using a questionnaire approach. This could aid prioritising patients at high risk of having oesophageal cancer for endoscopy. Our tool could help address endoscopic backlogs caused by the COVID-19 pandemic.

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Treatment of portal vein thrombosis in cirrhosis: a multicenter real life cohort study (2023)

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Type of publication:
Journal article

Author(s):
Mantaka A; Gatselis N; Triantos CK; *Thalheimer U; Leandro G; Zachou K; Konstantakis C; Saitis A; Thomopoulos K; Kouroumalis EA; Dalekos GN; Samonakis DN

Citation:
Minerva gastroenterology. 69(1):107-113, 2023 Mar.

Abstract:
BACKGROUND: Portal vein thrombosis (PVT) is a common complication of cirrhosis and can be a cause or consequence of liver disease progression. It is unclear whether PVT treatment is affecting clinical outcomes in cirrhotics. METHODS: This is a multicenter study of cirrhotics with PVT, initially retrospectively and thereafter prospectively registered in a data base. We studied the impact of PVT treatment on this population for efficacy, safety and the impact on survival. In survival analysis Mantel-Cox and Wilcoxon-Breslow-Gehan tests were used. A P value of <0.05, was considered significant. For statistical computations the STATA 12.1 was used.

RESULTS: Seventy-six patients were included (76% decompensated, median MELD score 12 and Child-Pugh score 7), 47% with concomitant HCC. Fifty-one patients with PVT were treated with Vitamin-K antagonists or Low-Molecular-Weight Heparin. Patients were followed up for at least 6 months after PVT diagnosis, or until death or transplantation. PV patency after 6 months was not  statistically different between patients receiving or not anticoagulation (complete-partial recanalization 27.4% of treated vs. 20% of untreated, P=0.21). Median survival was statistically worse between patients treated with anticoagulation than those untreated (10 vs. 15 months, P=0.036). Less portal hypertensive bleeding and less decompensation rates were found in treated cirrhotics vs. untreated (45.8% vs. 54.2%, P=0.003 and 78% vs. 80.9%, P=0.78, respectively). Patients with HCC had worse survival when treated vs. untreated (P=0.047).

CONCLUSIONS: In our cohort of cirrhotics with PVT, treatment was feasible with acceptable side effects, but without meaningful clinical benefits.

Treatment and outcomes of patients with gastrointestinal toxicity following immunotherapy: A large multi-center retrospective study in the United Kingdom by the National Oncology Trainees Collaborative for Healthcare Research (NOTCH) (2022)

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Type of publication:
Conference abstract

Author(s):
Swaminathan M.; Angelakas A.; Baxter M.; Cotton J.; Dobeson C.B.; Feeney L.; Gault A.C.; Hughes D.J.; Jones C.; Lee R.; Mughal S.A.; *Parikh S.P.; Pritchard M.; Rodgers L.J.; Rowe M.P.; Salawu A.T.; Shotton R.; Tinsley N.; Tivey A.; Olsson-Brown A.C.;

Citation:
Immuno-Oncology and Technology. Conference: ESMO Immuno-Oncology Congress 2022. Geneva Switzerland. 16(Supplement 1) (no pagination), 2022. Article Number: 100230. Date of Publication: December 2022.

Abstract:
Background: Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of many cancers, but their use has been associated with the development of gastrointestinal (GI) toxicities such as colitis and hepatitis. Method(s): A multi-center retrospective study across 12 National Health Service centers across the United Kingdom (UK) was conducted by the UK National Oncology Trainees Collaborative for Healthcare Research (NOTCH) over a 2-year period. The study included patients receiving ICIs for malignant melanoma, non-small lung cancer and renal cell cancer as standard of care. Occurrence of clinically significant (>=grade 2) GI toxicity was assessed and correlated with subsequent treatment and outcomes. Multiple logistic regression was used to assess correlation. For overall survival (OS), Kaplan-Meier and log-rank tests were utilised. Result(s): The cohort included 2049 patients. 1230 (60%) were male with a median age of 66. Colitis occurred in 182 (8.9%) patients and hepatitis in 129 (6.3%). Of the patients where treatment was recorded, 129 (70.9%) received treatment with systemic steroids alone and 37 (20.3%) required second-line immunosuppressants (IS) in the colitis group. In the hepatitis group, 101 (78.3%) had steroids alone with 19 (14.7%) having IS. Improved OS was found in patients who experienced colitis (HR 2.59 95%CI: 2.15 to 3.11, p<0.0001) and hepatitis (HR 2.26, 95%CI: 1.84 to 2.79, p=<0.0001) compared to those with no adverse events. Pre-existing autoimmune disease (p=0.02) and combination ICIs (p=0.006) were predictors of colitis that required IS whilst grade 2 and 3 hepatitis (p<0.001) were predictors of hepatitis needing IS. The use of IS did not affect OS significantly in the colitis group (p=0.372) but did correlate with survival in the hepatitis group (p=0.037). Patients that were able to continue treatment with ICIs after toxicity had an increased OS in both groups (p<0.001). Conclusion(s): Patients with GI toxicity following treatment with ICIs have improved OS. The use of IS did not significantly affect OS which suggests they should continue to be utilised in the treatment of GI toxicity. Legal entity responsible for the study: United Kingdom National Oncology Trainees Collaborative for Healthcare Research (NOTCH).

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Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation (2021)

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Type of publication:
Conference abstract

Author(s):
Grossi U.; *Lacy-Colson J.; Brown S.; Cross S.; Eldridge S.; Scott S.M.; Taheri S.; Knowles C.

Citation:
Colorectal Disease. Conference: 16th Scientific and Annual Meeting of the European Society of Coloproctology, ESCP 2021. Virtual. 23(Supplement 2) (pp 3), 2021. Date of Publication: October 2021.

Abstract:
Aim: Effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse (IRP) is poorly evidenced. A UK-based multicentre randomized controlled trial (RCT) was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. Method(s): A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR with those who had undergone surgery.Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to 3 arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was measured as a 1.0-point reduction in PAC-QOL and PAC-SYM scores at 24 weeks. Secondary outcome measures included 14-day diary data, GAD7, PHQ9, St Marks incontinence score, PISQ12, CC-BRQ, and BIPQ. Result(s): Of 42 eligible patients, 28 (67%) females were randomized from 6 institutions. Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the 3 arms. Compared to baseline, significant reduction in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (-1.09 [95%CI -1.76, -0.41], P = 0.0019, and -0.92 [-1.52, -0.32], P = 0.0029). As opposed to PAC-QOL (-1.38 [-2.94, 0.19], P = 0.0840 at 72 weeks), improvements in PAC-SYM scores persisted to 72 weeks (-1.51 [-2.87, -0.16], P = 0.0289). Compared to baseline, no differences were found on secondary outcomes, except for significant improvements on CC-BRQ and BIPQ at 24 and 48 weeks. Conclusion(s): There was evidence of a short-term effect of LVMR for IRP up to 36 weeks. Improvements in quality of life declined over follow-up up to 72 weeks.

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Results of an audit of the Peristomal Body Profile Assessment Tool (2022)

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Type of publication:
Journal article

Author(s):
*Nicola Tonks Natasha Rolls, Kimberly Bain, Paul Russell-Roberts and Mark Bain

Citation:
British Journal of Nursing, December 2022, Vol 31, No 22, S4-S12 (Stoma Care Supplement)

Abstract:
Background: Leakage is the number one concern for people with an ostomy. The 2019 Ostomy Life Study, a global study of more than 5000 ostomates, showed that 92% of people living with a stoma worry about leakage. Getting the right stoma appliance for each patient is key to increasing patient quality of life. Aim: The study was designed to assess the use of the PeristomalBody Profile Assessment Tool in helping choose the most appropriate stoma products for a given patient, decreasing incidents of leakage and peristomal skin complications. Methods: A multi-centre (33 sites, 147 patients) low-interventional clinical investigation was conducted in which the use of the Peristomal BodyProfile Assessment Tool was evaluated as a tool to reduce incidents of leakage, increase peristomal skin health and increase patient quality of life. A focus group of randomised participating clinicians (n=16) was held to explore the audit results. Results: The assessment tool most often took between 2 and 5 minutes to complete. It supported clinicians in selecting the right appliance for each patient, avoiding leakages and preventing associated peristomal skin complications. The assessment tool helped improve the accuracy and quality of documentation in the patients’ medical/nursing notes, increasing the quality and continuity of care. Participants reported that using the assessment tool helped reduce care costs by reducing the need for product changes, supporting product usage and return patient visits. Conclusion: Use of the Peristomal Body Profile Assessment Tool helped clinicians choose the most appropriate stoma appliance the first time, resulting in patients having healthier peristomal skin, fewer leakages, more confidence in their stoma appliance and a higher quality of life.

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Laparoscopic ventral mesh rectopexy for pelvic floor dysfunction is a safe procedure: a single centre experience (2022)

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Type of publication:
Conference abstract

Author(s):
*Chang J.; *Rajalingam V.; *Ebanks A.; *Lacy-Colson J.; *Farquharson A.

Citation:
Colorectal Disease. Conference: Association of Coloproctology of Great Britain and Ireland Annual Meeting. Edinburgh United Kingdom. 24(Supplement 2) (pp 65), 2022. Date of Publication: September 2022.

Abstract:
Purpose: Laparoscopic Ventral Mesh Rectopexy (LVMR) is an established treatment option in the management of internal and external rectal prolapse. However, there is some concern regarding the safety and long-term outcomes of the use of mesh in the pelvis. The Pelvic Floor Society (TPFS) has suggested a move towards delivering this surgery in accredited units in the UK. We present our experience and outcomes for LVMR where a standardised technique is performed. Method(s): All patients who underwent LVMR between 2012 and 2020 at a single centre were included. Clinical indications for surgery, preoperative proctogram, endoanal ultrasound, anorectal physiology, pre and postoperative symptom severity scoring (Longo and Wexner) and outcome data were collected and analysed. Result(s): 146 patients underwent LVMR during the study period. Indications included; faecal incontinence (FI) (5), obstructive defecation syndrome (ODS) (74), mixed ODS/FI (34), and external rectal prolapse (32). One patient required re-operation for vaginal erosion of mesh suture (4 years post-LVMR). No other mesh complications were identified. 100 patients had resolution of symptoms, 46 had symptomatic improvement but required ongoing therapies (rectal irrigation, laxatives or biofeedback therapy). Ten patients underwent subsequent sutured transanal mucosal repair or haemorrhoidectomy for ongoing symptoms of ODS. Two patients developed recurrence of external prolapse which required operation: Delorme's (1), repeat LVMR (1). Conclusion(s): LVMR is a safe and effective procedure for pelvic floor dysfunction and the treatment of internal and external rectal prolapse in selected patients. Undertaking a standardised procedure in high volume units ensures optimal patient outcomes.

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Comparative analysis of gene mutations present in rectal mucus sampled using the OricolTM and DNA retrieved from the Paired Formalin-Fixed Tumour Blocks. Early Data from the OricolTM EGI-02 Study (2022)

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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]