Introduction

Colonoscopy is a well-established screening tool for detection of colorectal lesions. Colonoscopy waiting lists can last for months, however, the rates of unperformed procedures due to patients' absence ('no-show') are 8-15% globally.

Aims & Methods

The aim of this study was to evaluate whether a personalized digital platform would reduce 'no-show' rates for ambulatory colonoscopies.
We retrospectively analyzed prospectively collected data regarding scheduled ambulatory colonoscopies. The GistMD digital platform includes a patient-tailored animated video, individualized according to age, gender, comorbidities and language. It also includes links to written instruction forms and consent forms, and a set of reminders. During 01/2022-06/2022, a link to the GistMD system was randomly sent to patients before a scheduled colonoscopy. The study group ('GM-Link') included all patients that were sent the link by SMS. The control group received standard written instructions by email.

Results

During the study period, a total of 2114 colonoscopies were included. The GistMD link was randomly sent to 1621 (76.7%) patients ('GM-Link') and standard written prepration instructions to 493 (23.3%) controls ('No link').
The 'no-show' rates were reduced by half among the 'GM-Link' group compared to controls [190 (11.7%) vs. 114 (23.1%), respectively, p<0.001]. This significant 'no-show' rate reduction in the 'GM-Link' group compared to the 'No Link' group was consistent among males and females subgroups analysis (11.8% vs. 27.5%, p<0.001 and 11.7% vs. 19.3%, p=0.003, respectively) and among all age groups (p<0.05, for all groups). Furthermore, the 'GM-Link' group was divided according to usability: 1. 'No video' - Video was not watched at all, 757/1621 (46.7%), 2. 'Min users' - Watched<75% of the video,77/1621 (4.8%) and 3. 'Max users' - Watched >75% of video, 787/1621 (48.6%). There was a "dose-dependent" trend between usability groups and 'no-show' rates: 'No link' - 23.1%, 'No video'-17.4%, 'Min users' -10.4%, 'Max users'- 6.4% (P<0.001).
In two multivariate logistic regression adjusted for age, sex and morning vs. afternoon colonoscopy, 'GM-Link' receivers and 'Max users' were each independently associated with 51% and 76% 'no show' rate reduction compared to 'No link' controls (OR 0.491, P<0.001 and OR 0.242, p<0.001, respectively). According to number needed to treat analysis, the number of sent links required for prevention of one 'no show' was 8 links. In terms of economical calculations, using the digital platform will reduce the monthly income loss due to 'no-show' by ~70,000 ILS (~17,550 euro) and the yearly income loss by ~840,000 ILS (~210,500 euro), considering 400 colonoscopies/month of which 35% include polypectomy.

Conclusion

Implementation of a digital platform significantly reduced 'no show' rates for ambulatory colonoscopy. This reduction can result in increased efficiency and reduced financial losses as well as shorter waiting times in gastroenterology units.

Introduction

IL-6 is implicated in the pathogenesis of ulcerative colitis (UC), however no IL-6 inhibitor has been approved for UC to date. Selective inhibition of IL-6 trans-signaling could ameliorate the deleterious, pro-inflammatory effects of IL-6¹,while preserving the homeostatic, tissue reparative activity of classical IL-6 signaling. Olamkicept ², a fusion protein consisting of two complete extracellular domains of gp130 attached to the Fc-region of an IgG₁ antibody, neutralizes IL-6 trans-signaling in vitro and has shown promising clinical effects in a recent randomized, double-blind, placebo-controlled phase II trial in moderate to severe UC (NCT03235752)³.

Aims & Methods

The objective of this study was to characterize the biological effects resulting from selective inhibition of IL-6 trans-signaling using an in silico model of colonic inflammation.
A hybrid mechanistic-statistical computational model of colonic inflammation in UC was developed using published pre-clinical and clinical studies as well as internally generated in vitro pharmacology data^2-4. The output of the model included changes in IL-6 signaling pathway components (IL-6, soluble IL-6 receptor, membrane-bound IL-6 receptor, soluble gp130, and STAT-3 phosphorylation), C-reactive protein (CRP), fecal calprotectin, adaptive immune cell (CD4+ T lymphocyte) sub-populations, cytokines, and chemokines. States of tissue damage and repair (healing) were estimated.
The performance of the model was tested against clinical data generated in NCT03235752³ in which patients had been allocated to receive intravenous (IV) administration of 300 mg or 600 mg olamkicept or placebo every two weeks for 12 weeks.
Simulations assessing the differential effects of modulating trans- and cis-signaling were probed using pharmacological inhibitors of trans- (olamkicept, 300-1800 mg administered IV every 2 weeks) and pan-IL-6 signaling (IL-6 receptor inhibitor and a STAT-3 phosphorylation inhibitor). Changes in concentrations of IL-6 signaling species and down-stream effects on immune cell sub-population levels were compared both in the systemic circulation and locally in the gut tissue. The initial concentrations of the signaling species were based on those typically observed in UC patients⁵.

Results

Based on the simulations, concentrations of free IL-6 in the systemic circulation were minimally impacted by exposure to olamkicept. In gut tissue, IL-6 concentrations decreased by approximately 10% at the highest olamkicept dose tested, returning to pre-treatment levels within a day post dose.
Suppression of IL-6 trans-signaling by olamkicept caused a transition away from aT_h17-rich state in gut tissue and attenuated inflammatory chemotactic signals in a dose-dependent manner. In comparison, the pan-inhibition of IL-6 signaling reduced T_h17 mediated inflammatory activity, however tissue healing pathways dependent on IL-6 cis-signaling were also suppressed.

Conclusion

In the developed in silico model of colonic inflammation, inhibition of IL-6 signaling was associated with attenuation of T_h17 mediated inflammation in the gut. Pan-inhibition of IL-6 signaling was associated with impaired tissue healing, however this was not observed for olamkicept, where homeostatic, classical IL-6 signaling was preserved.
This study provides quantitative support to therapeutic strategies targeting IL-6 trans-signaling in UC to reduce the cytokine’s undesirable effects while preserving its beneficial functions.

References

1. Garbers C. et al., The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition. Curr Opin Immunol. 2015 Jun;34:75-82. doi: 10.1016/j.coi.2015.02.008.
2. Schreiber S. et al., Therapeutic Interleukin-6 Trans-signaling Inhibition by Olamkicept (sgp130Fc) in Patients With Active Inflammatory Bowel Disease. Gastroenterology. 2021 Jun;160(7):2354-2366.e11. doi: 10.1053/j.gastro.2021.02.062.
3. Zhang S, et al., Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis: A Randomized Clinical Trial. JAMA. 2023 Mar 7;329(9):725-734. doi: 10.1001/jama.2023.1084.
4. Reeh H. et al. Response to IL-6 trans- and IL-6 classic signalling is determined by the ratio of the IL-6 receptor α to gp130 expression: fusing experimental insights and dynamic modelling. Cell Commun Signal. 2019 May 17;17(1):46. doi: 10.1186/s12964-019-0356-0.
5. Nikolaus S et al. Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases. Int J Colorectal dis. 2018 Jul;33(7):927-936. Doi: 10.1007/s00384-018-3069-8

Disclosure

O. Sternebring, A. Ravi, A. Rivollier, S. Read, R. Szabady and P. Pinton are employees of Ferring Pharmaceuticals. P. Pinton owns stocks of Takeda Pharmaceutical Company Limited. N. Patidar, R. Carcillo, M. Behar, Jørgen Sørensen and P. D’Alessandroare employees of PriceWaterhouseCoopers.

Introduction

Colorectal carcinoma (CRC) is one of the most important indications for colorectal surgery despite the availability of screening measures. Anastomotic leakage is among the most common potentially life-threatening complications. Increasing evidence suggests a causal role of the gut microbiota in the pathogenesis of anastomotic leakage.

Aims & Methods

The aim of the study was to evaluate the dynamics of microbiome changes in patients with colorectal carcinoma before, during and after surgical intervention in relation to anastomotic insufficiency. From a total of 18 patients recruited, the records of 16 patients were systematically analysed according to inclusion/exclusion criteria and sequencing quality. Biopsies were taken from the 3 sites (proximal to the tumour, tumour region, distal to the tumour) before, during and after surgery. All patients received preoperative Metronidazole and Paromomycin for intraluminal bowel decontamination and a single intravenous dose of Ertapenem during surgery. DNA extraction was followed by amplification of the V1-V2 region of the 16S rRNA gene and Illumina sequencing.

Results

Phocaeicola, Prevotella and Enterococcus were the most abundant of the 259 different genera found in the cohort. Hierarchical clustering showed that samples from the same patient at the same time point generally had high similarity (66%), and in 6 cases all samples from more than one time point formed a cluster. These results were corroborated by comparing the Bray-Curtis similarity of sample sites and time points. Periinterventional procedures were associated with a significant decrease in diversity in samples collected during or after surgery. Samples with anastomotic leakage had a different microbial structure at all time points, with Prevotella being more abundant in the anastomotic leakage group (p<0.0001), whereas Phocaeicola was more abundant in the sufficient anastomosis group (p=0.04). Systematic longitudinal analysis revealed an increasing abundance of bacterial species, particularly Enterococcus and Escherichia/Shigella, at subsequent sampling times.

Conclusion

The mucosal microbiota is substantially altered by colorectal surgery, and the microbiome of patients with anastomotic leakage differs from that of patients with sufficient anastomoses. Further studies are needed to unravel the molecular and functional interactions between the microbiota and mucosal tissue.

Introduction

Post-colonoscopy colorectal cancer (PCCRC) is that diagnosed after a colonoscopy in which no cancer is found. PCCRC has become an important quality indicator. We aimed to determine its rates, characteristics, and index colonoscopy-related predictive factors.

Aims & Methods

Multicenter, observational, retrospective study between 2015 and 2018. We considered as PCCRC those developing up to 10 years after colonoscopy. PCCRC rates were calculated and PCCRC were categorized according to their most plausible explanation using the World Endoscopy Organization (WEO) methodology. Our PCCRC population was compared to a control cohort without CRC matched 1:4 by sex, age, index colonoscopy date and indication, endoscopist, and hospital.

Results

107 PCCRC were detected, of 101,524 colonoscopies (0.1%) and 2,508 CRC (4.3%), leading to rates of 0.4% (1-year), 2.2% (3-year), 3.1% (5-year), 4.1% (10-year). PCCRCs were in right (42.4%), left (41.4%), transverse (16.4%) colon with 31.5% at stage I, 24.7% stage II, 32.6% stage III, 11.2% stage IV. 20.3% of PCCRCs were classified as incomplete resection, 5.4% as unresected detected lesions, 48.6% as missed lesions with adequate colonoscopy, and 25.7% as missed lesions with inadequate colonoscopy. Mean time from previous colonoscopy to PCCRC was 42 months. Previous inadequate preparation (OR 3.05, 95%CI 1.73-5.36) and piecemeal polypectomy (OR 19.89, 95%CI 8.67-45.61) were independently associated with PCCRC.

Conclusion

In our population, 4.3% of CRCs were PCCRC. Most of these lesions were in the right colon and almost half attributable to lesions not visualized despite adequate bowel cleansing. Previous inadequate cleansing and piecemeal polypectomy were associated with PCCRC.

Disclosure

RJ has received research grants from MSD, and has participated as an advisor to MSD, Norgine, Alpha-Sigma, and GISupply. The rest of authors have nothing to disclose.

Introduction

Volatile organic compounds (VOCs) form a specific chemical profile that can be used to detect the colorectal cancer-related changes in human metabolism and thereby, to diagnose this type of cancer even at an early stage.

Aims & Methods

The aim of this study was to characterize the volatile chemical patterns associated with cancer and normal tissues obtained from colorectal cancer patients and identify potential volatile biomarkers of colorectal cancer. In total 50 paired tissue samples were analyzed. Volatiles released by the tissue samples were captured using solid phase microextraction (HS-SPME) and next identified and quantified using gas chromatography with mass spectrometric detection (GC-MS). A Wilcoxon signed-rank test was used to compare the emissions of VOCs from cancer and non-cancerous tissues and p<0.05 was taken as significant threshold.

Results

A total of 163 compounds were found in the headspace of the tissue samples. Amongst these, 149 VOCs were identified in cancer tissues and 147 in non-cancerous ones. 138 volatiles were found in both types of tissues. The predominant chemical classes in both tissues are hydrocarbons (25%) and alcohols (15%). These are followed by aldehydes, ketones and aromatics. Only 40 VOCs (27%) exhibited incidence higher than 50% in cancerous tissues. In case of healthy tissue this number amounted to 44 (30%). 11 volatiles occurred in at least 90% of both types of samples and thereby can be considered as omnipresent. 15 VOCs showed consistent differences in their headspace concentrations above samples under study. Of these, 4 compounds were found to have increased emissions from the cancer tissue, and the other 11 showed the reduced release from this type of samples. The species emitted in higher amounts by cancerous tissue comprised 1-propanol, pyridine, isoprene and methyl thiolacetate (p<0.05).

Conclusion

The results of this study confirm that the chemical fingerprint formed by volatiles in colorectal tissue is altered by colorectal cancer. These VOCs - 1-propanol, pyridine, isoprene, methyl thiolacetate were found to be the most promising biomarker candidates for detecting colorectal cancer.

Introduction

Filgotinib is a selective JAK1 inhibitor recently licensed for use in moderate-severe Ulcerative Colitis (UC)​¹​​​​.

Aims & Methods

We sought to review outcomes for patients commenced on Filgotinib for UC in the Glasgow South Sector IBD Service. Patients were identified using the local IBD Biologics Database. Electronic patient records were reviewed for demographics, previous treatment, and outcomes since commencing Filgotinib.

Results

28 patients were commenced on filgotinib between July 2022 and February 2023. 21.4% were female and 78.6% male with a median age of 38y. By Montreal classification, 3.6% were classified as E1, 64.3% as E2 and 32.1% as E3. 50% of patients were biologic naïve with 71.4% on concomitant treatment with aminosalicylate. Median follow-up was 4 months.
78.6% (22/28) reported improvement in their symptoms with only 21.4% (6/28) experiencing side effects (SEs). 64.3% in the biologic-naïve group found subjective improvement in symptoms with 85.7% noting improvement in the biologic-experienced group. SEs included infections (3), Increase in cholesterol/triglycerides (2) and subjective worsening of low mood (1).
17 Patients had pre and post-treatment Faecal calprotectin (FC) available. Of those patients, 70.6% had an improvement with an overall reduction in median FC level from 1567 to 203 across the group. This reduction did not reach statistical significance.
7/28 patients required a course of rescue steroids after starting treatment. No patients required IP admission since commencing treatment. 5/28 were considered to have a primary non-response to Filgotinib. Of these, 4 were switched to alternative advanced therapies and 1 awaits surgery.

Conclusion

Filgotinib appears a safe and effective treatment in moderate-severe UC for both biologic-naïve and experienced patients. Its oral route of administration and quick onset mechanism of action make it an appealing choice. Further real-world data is required with larger patient cohorts to establish its true utility in routine clinical practice.

References

1. D’Amico, F. et al. (2021) “Positioning Filgotinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis,” Journal of Crohn’s and Colitis, 16(5), pp. 835–844. Available at: https://doi.org/10.1093/ecco-jcc/jjab206.

Introduction

Cold snare polypectomy (CSP) has become popular as a safe and simple treatment for small colonic lesions. According to the Japanese guidelines, CSP is indicated for adenomas <10 mm with no suspicion of carcinoma [1]. Occasionally, colorectal carcinoma is diagnosed after resection, and there is no consensus on the treatment of such lesions [2-4].

Aims & Methods

This single-center retrospective study aimed to investigate the long-term prognosis of Japanese patients with pathologically diagnosed colorectal carcinoma after resection by CSP. Patients who underwent CSP for small colonic lesions at our hospital in 2013–2022 and were histopathologically diagnosed with colorectal carcinoma were included in this study. We examined the local residual or recurrence rate, scar detection rate, and recurrence-free survival rate in patients who underwent at least one colonoscopy after CSP.

Results

Out of 12,935 lesions (6,082 cases) that were resected using CSP during the study period, 81 lesions (0.63%; 81 cases) were histologically diagnosed as colorectal carcinoma (mean age, 69.7 years; male patients, 69% [56/81]). Histologically, all tumours were well-differentiated adenocarcinomas. Negative lateral and vertical margins of the resected specimens were 47% (38/81) and 72% (58/81), respectively. Of these 81 cases, 47 (58%) were followed up at least once by colonoscopy. The breakdown of cases that were not followed up endoscopically is as follows: concurrent advanced cancer (n=15), advanced age (n=7), dropout (n=7), and others (n=5). Endoscopic evidence of residual disease or recurrence was found in 1/47 patients (2%), and the remaining 46 patients had a median colonoscopic follow-up of 425 days (interquartile range, 192.5–1078.5 days) with no endoscopic evidence of local recurrence. In 51% (24/47) of cases, post-polypectomy scars could be identified. In one case where local residual carcinoma was confirmed, a retrospective review of the CSP revealed incomplete resection at the time of treatment. Abdominal CT performed immediately after CSP showed coincidental peritoneal dissemination, and the patient died 177 days after diagnosis. In 46 patients with no endoscopic evidence of local recurrence, the median observation period was 921 days (interquartile range, 475–1654.5 days), with six cases of death from causes other than colorectal cancer, and the others were alive without recurrence.

Conclusion

The frequency of residual disease or recurrence of colorectal carcinoma treated by CSP was low, and the long-term prognosis was favourable once the absence of residual lesions was confirmed endoscopically.

References

1. Uraoka T, Takizawa K, Tanaka S et al. Guidelines for Colorectal Cold Polypectomy (supplement to "Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection"). Dig Endosc 2022; 34: 668-675.
2. Yoshii S, Hayashi Y, Nakamura T et al. Endoscopic features and clinical course of colorectal carcinoma resected by cold snare polypectomy. J Gastroenterol Hepatol 2023, in press
3. Inoki K, Takamaru H, Furuhashi H et al. Management of colorectal high-grade dysplasia or cancer resected by cold snare polypectomy: a multicenter exploratory study. J Gastroenterol 2023, in press
4. Yoshida N, Fukumoto K, Hasegawa D et al. Recurrence rate and lesions characteristics after cold snare polypectomy of high-grade dysplasia and T1 lesions: A multicenter analysis. J Gastroenterol Hepatol 2021; 36: 3337-3344.