Gastroenterology

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.

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Reduction in rates of reversal of temporary stoma after anterior resection, another building crisis post COVID-19? (2022)

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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.

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Resection and primary anastomosis in perforated diverticulitis: Selecting the right operation for the right patients (2022)

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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.

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Rectal mucus protein collection using the OricolTM sampling device: Comparison of calprotectin levels in stool and rectal mucus in patients with suspected or confirmed inflammatory bowel disease (Oricol-EGI- 01 Study) (2022)

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Type of publication:
Conference abstract

Author(s):
*Jones, G.

Citation:
Colorectal Disease. Conference: Association of Coloproctology of Great Britain and Ireland Annual Meeting. Edinburgh United Kingdom. 24(Supplement 2) (pp 58), 2022. Date of Publication: September 2022.

Abstract:
Background: Faecal calprotectin testing is recommended by the National Institute for Health and Care Excellence (NICE) to distinguish between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) after cancer exclusion. Many patients do not produce faecal samples as requested and therefore a direct collection technique may have a role in IBD diagnosis or monitoring. We compared the performance of faecal and rectal mucus calprotectin collected with the OriColTM sampling device Methods: Sixty-six patients with confirmed or suspected IBD were recruited in the Oricol-EGI- 01 Study. OriColTM and matched stool samples were collected and processed following standard operating procedures. Calprotectin concentrations were measured using IDK Calprotectin and fCAL assays Results: Calprotectin was detectable in the OriColTM samples with good discrimination across the calprotectin assays and discernible correlation to corresponding faecal calprotectin concentrations Using thresholds determined for rectal mucus calprotectin (calculated by linear regression), the percentage agreement between calprotectin concentrations in stool and rectal mucus for patients with faecal calprotectin >=50 mug/g was between 68% and 91% with a percentage agreement at <50 mug/g between 40% and 71% with IDK Calprotectin and fCAL assays respectively. Good agreement was observed for IBD patients with the results being above the threshold for both faecal and rectal mucus calprotectin with 93% and 86% for IDK Calprotectin and fCAL assays respectively Conclusion(s): The OriColTM Calprotectin Kit was successfully used to collect rectal mucus and measure calprotectin concentrations with positive correlation to corresponding faecal calprotectin and is potentially a new and acceptable modality in IBD patients.

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An internal pilot study of a novel rectal mucocellular sampling device to allow next-generation sequencing for colorectal disease (2023)

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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 OriColTM 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-iTTM 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 OriColTM sampling procedure and 285/290 (98.27%) had a successful OriColTM 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 OriColTM 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.

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Intussusception of the Appendix in a Young Adult with Cystic Fibrosis: An Important Differential Diagnosis of Abdominal Pain in Cystic Fibrosis Patients? (2022)

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Type of publication:
Conference abstract

Author(s):
*Venkatasami M.; *Cobby E.

Citation:
British Journal of Surgery. Conference: ASiT Surgical Conference 2022. Aberdeen United Kingdom. 109(Supplement 6) (pp vi57), 2022. Date of Publication: September 2022.

Abstract:
Background: Cystic fibrosis (CF) is commonly associated with gastrointestinal manifestations from infancy to adulthood. Intussusception in the paediatric CF population is widely reported, whereas in the adult, distal intestinal obstruction syndrome (DIOS) is common affecting 20%, of which, intussusception is rare and appendiceal intussusception is rarer, affecting 1%. Case-Description: A 20-year-old male with CF presented with 3 days of right iliac fossa pain and diarrhoea. On admission, he was hypotensive and afebrile. Clinical examination revealed tenderness of the right flank with a palpable mass in the right iliac fossa. Serum investigations showed mildly raised inflammatory markers. Contrast CT of the abdomen-pelvis confirmed intussusception of the appendix into the ascending colon. Histological analysis of the appendix further demonstrated intussusception, with intraluminal mucinous material. Fascinatingly, no transmural inflammation was present. The patient underwent a laparotomy-open appendicectomy. Interestingly, intraoperative findings showed the intussusception resolved, no longer requiring surgical reduction. Patient postoperative recovery was complicated by pneumonia for which he was transferred for specialist CF respiratory care and thereafter, discharged. Discussion(s): Literature review highlighted a paucity of data, with 10 reported cases of appendiceal intussusception in adult CF patients. Interestingly, we report the intussusception had reduced by the time of operation. This is in-keeping with previous case reports of transient intussusception which spontaneously resolved. Conclusion(s): From this rare case presentation, we have learnt it is imperative to carry a high index of suspicion for gastrointestinal manifestations in CF patients where acute appendicitis is seen less often and differential diagnoses like DIOS and intussusception should be considered.

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