Introduction

Post-Faecal Immunochemical Test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas, mostly due to distal pedunculated polyps. Due to an expected higher risk of Colorectal Cancer (CRC), post-polypectomy surveillance is recommended, generating a substantial overload on endoscopy services. The aim of our study was to investigate the post-polypectomy CRC incidence risk in a screening population of FIT+ subjects after resection of low- (LRA) or high-risk adenomas (HRA).

Aims & Methods

We retrieved data from a cohort of patients undergoing post-polypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 followed-up to December 2021. Main outcomes were post-polypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia and location of the index lesion. We adopted FIT- subjects as comparators. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables.

Results

Overall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had a LRA and 22,709 (26.0%) a HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (Hazard Ratio [HR] 1.15, 95% Confidence Interval [CI] 0.93-1.42) risks were not increased compared to the FIT-negative group, while for HRAs a significant increase in CRC incidence (HR 1.49, 95% CI 1.20-1.86) risks were found. The presence of one or more risk factors among proximal location, non-pedunculated morphology and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR 1.75, 95% CI 1.37-2.25). Patients with only distal pedunculated polyps without HGD, representing 39.2% of HRA, did not show any increased risk compared to the FIT-negative group (HR 0.84, 95% CI 0.60 - 1.17).

Conclusion

CRC incidence is significantly higher in patients with high-risk adenomas diagnosed at colonoscopy. However, such excess risk does not apply to patients with only distal pedunculated polyps without HGD, substantially reducing the burden of surveillance in FIT programs.

Disclosure

no COI

Introduction

A good bowel preparation for colonoscopy is fundamental to improve the quality of the examination, reduce procedural complications and achieve optimal polyp detection. Among possible strategies to enhance bowel preparation, visual booklets have been proposed with conflicting results. Therefore we aimed to perform a systematic review with meta-analysis of randomized controlled studies (RCT) to ascertain whether booklets may be useful in this setting.

Aims & Methods

Literature search was performed in July 2022, in main databases (PUBMED, SCOPUS, ScienceDirect, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov). only RCTs were selected. The primary outcome was the quality of bowel preparation. Further outcomes were the adenoma detection rate (ADR), number of polyps detected per patient, rate of cecal intubation, time of insertion and withdrawal, adverse events, willingness to repeat preparation and colonoscopy. We estimated odd ratios (OR) for dichotomous outcomes. mean differences (MD) or standardized mean differences (SMD) were used for continuous outcomes. We estimated heterogeneity among studies with the Chi2 (Cochran Q) and the I2 statistics. In case of high heterogeneity, a random effect model was used, otherwise a fixed effects model was preferred. All analyses were performed using RevMan version 5.4.1.

Results

Six studies were selected, enrolling overall 1755 patients (857 in the booklet and 898 in the control group). Adequate bowel preparation was achieved in the 86.7% (743 out of 857) of booklet preparation versus the 77.5% (696 out of 898) in the control group, with an OR of 2.31 in favour of booklet (95% CI 1.20-4.45, p = 0.01). Booklet was more effective than control in the transverse colon (MD = 0.37, 95% CI 0.01-0.72, p = 0.03), while no differences were found in right colon and left colon. In four studies a 4-L PEG-based preparation was used and the pooled analysis did not find any difference compared to controls, while when sodium phosphate and magnesium citrate or sodium phosphate or PEG were used, preparation with booklet was better than in controls (OR = 5.10, 95% CI 1.82-14.27, p = 0.002). Two studies were performed in inpatient setting, without difference between booklet and controls while in outpatients patients receiving booklets were better prepared than controls (OR = 7.13, 95% CI 5.39-9.45, p < 0.001). ADR was similar between the two groups, with an OR = 0.93 (95% CI 0.75-1.16, p = 0.53). The mean number of polyps per patient did not differ between the two groups (MD = 0.22, 95% CI -0.14-0.58, p = 0.23).

Conclusion

The present meta-analysis demonstrated that booklets are useful to enhance bowel preparation. Outpatients and non PEG-based preparations seem to benefit more from booklets, while no effect on ADR has been observed.

Introduction

Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by corpus-restricted atrophy and pseudopyloric or intestinal metaplasia, associated with reduced hydrochloric acid and intrinsic factor production and heterogeneous clinical consequences. The aetiology of AAG is autoimmune, but the role of Helicobacter pylori (Hp) has been proposed, although not definitively proven. A possible antigenic crossreactivity with H+,K+-ATPase, the main autoantigen in AAG, has been reported and Hp seropositivity has been described in histologically Hp negative AAG. One study employed molecular biology techniques to characterize a cohort of AAG patients as definitively Hp naïve.

Aims & Methods

The aim was to assess the presence of Hp-related genes in corpus mucosa biopsies of pts with AAG and Hp-positive and negative ctr by using real-time PCR.
Single-centre, experimental molecular biology study on 55 pts with histologically diagnosed AAG, of whom at histology 52 were Hp negative (age 61.5, range 28-88 yrs, 75% F, 96.2% parietal cell (PCA) and 44.2% intrinsic factor antibodies (IFA) positive), while 3 were Hp positive (age 74,69,33 yrs; 1 F; all 3 PCA and 1 IFA positive). Ctr were 4 pts who underwent gastroscopy for non-ulcer dyspepsia, 2 with Hp-positive superficial antral gastritis (positive ctr), and 2 with a healthy stomach (negative ctr). Hp serology (ELISA or multiplex) was available from all pts. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue sections of corpus mucosa biopsies and real-time PCR was performed using specific probes for UreA, UreC, and CagA Hp related genes; 16sRNA and Beta2 microglobulin (B2M) specific probes were used as amplification ctr of bacterial and human DNA (real-time PCR cycle threshold (CT) >28<38).

Results

In 4(7.7%) of the 52 histologically Hp negative AAG pts, Hp-related genes were detected, in 4(7.7%) UreC, in 3(5.8%) UreA, and in 1(1.9%) CagA. All of them (3 F, aged 88,85,58,56 yrs) had positive Hp serology and PCA, only one was IFA-positive. The detectability of B2M and bacterial 16sRNA genes did not differ in UreC-positive or UreC-negative pts (B2M CT mean 29.6±1.2 for Ure-C positives vs 29.7±1.4 for Ure-C negatives, p=0.99; 16SrRNA gene CT mean 29.9±1.2 vs 29.4±1.2, p=0.27) indicating that the not-detectability of Hp-related genes was unrelated to reduced amounts of gastric bacterial or human DNA. Hp serology was positive in all 4 histologically Hp-negative AAG pts positive for UreC compared to 5/48(10.4%) UreC negative pts (p<0.0001) indicating previous exposure. PCA were present in all 4 UreC positive AAG pts compared to 46/48(95.8%) of UreC negatives (p=0.68). IFA positivity in UreC negatives was nearly 2x higher than that of UreC positives (45.8% vs 25%, p=0.42) without reaching significance. In 2/3 pts with histologically Hp-positive AAG, Hp-related genes could be detected; in the remaining patient, nor UreA, UreC neither CagA gene could be found (M, 69 yrs, no anemia, PCA-IFA-Hp serology positive).

Conclusion

In >90% of histologically Hp-negative and PCA or IFA positive AAG pts, Hp-related genes cannot be retrieved in the gastric mucosa. In 10% of these Hp-genes negative AAG pts, previous exposure to Hp can be testified by positive serology.
Hp-related genes can be detected in gastric biopsies in <10% of histologically Hp-negative AAG patients and positive Hp serology further confirms the role of Hp in this group.
These findings show that primary, Hp naive AAG is the more common type, but in a subset of pts, AAG seems to be secondary to Hp infection.

References

Lenti MV, Nature Rev Dis Primer 2020,
Lahner E, Dig Liv Dis 2019,
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Dottori L, UEGW 2023
Rugge M, Gut 2022

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

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

The incidence of early-onset colorectal cancer has been increasing worldwide, and action is urgently needed to address this problem. Although we have previously reported age-related changes with respect to molecular pathology, the vast majority remains unknown regarding the clinicopathologic characteristics of early-onset colorectal cancers and adenomas, especially those resected by endoscopic approaches. In this study, we defined early-onset colorectal tumors as adenoma and carcinoma diagnosed age at 40 or under. The aim of this study was to examine the clinicopathologic characteristics of endoscopically resected early-onset colorectal tumors compared with later-onset colorectal tumors diagnosed at age 40 or older.

Aims & Methods

We examined the clinicopathological characteristics of endoscopically resected colorectal adenomas and carcinomas in 1,005 patients with 2,367 lesions including early-onset colorectal carcinoma/adenoma (159 lesions in 96 consecutive cases from January 2010 to December 2020), late-onset colorectal carcinoma (183 lesions in 90 cases from January 2010 to December 2020), and late-onset adenoma (2,025 lesions in 819 consecutive cases from January 2020 to July 2020) endoscopically resected at the Nippon Medical School Hospital. The chi-square test was used to compare categorical variables, and the Mann-Whitney U test was used to compare continuous variables.

Results

Median age (quartiles) and sex (female/male) of cases were 37 (34-38), 34 (35%) / 62 (65%) in the early-onset tumor group; and 55 (46-72), 277 (30%) / 632 (70%) in the late-onset tumor group, respectively. The distribution rate of tumor location was 49 cases (31%) for proximal colon, 97 (61%) for distal colon, 13 (8.2%) for rectum in the early-onset group; and 1085 (49%), 899 (41%), 83 (10%) in the later-onset group, respectively. Macroscopic types were classified into Ip for 46 cases (29%), Is and Isp for 100 (63%), II for 13 (8.2%) in the early-onset group; and 278 (13%), 1574 (71%), 356 (16%) in the late-onset group, respectively. Histological types were classified into tubular adenocarcinoma or papillary carcinoma for 14 cases (8.8%), high-grade tubular adenoma (TA) for 36 (23%), low-grade TA for 97 (61%), sessile serrated lesion or traditional serrated adenoma for 12 (7.5%) in the early-onset tumor group; and 183 (8.3%), 281 (13%), 1655 (75%), 89(4%), respectively. Compared with the later-onset colorectal tumors, a higher rate of left-sided tumor location and macroscopic type Ip was observed in the early-onset colorectal tumor (p <0.001, respectively). When limited to adenoma lesions, the rate of high-grade was significantly higher in the early-onset colorectal adenomas than those in the later-onset colorectal adenomas.

Conclusion

Regarding tumor location and macroscopic type, unique clinicopathological features were observed in early-onset colorectal tumors compared with later-onset colorectal tumors. Further studies are needed to investigate the association between early-onset colorectal cancer and adenomas stratified by the method by tumor resection.

Introduction

The organized, population-based National Colorectal Cancer (CRC) Screening Program in the Czech Republic is focused on asymptomatic individuals aged over 50. There are two methods available. Fecal occult blood test (FOBT) is offered by general practitioners annually at ages 50 – 54 and biennially at age ≥ 55 (followed by FOBT+ colonoscopy, if positive). And screening colonoscopy from age 50, repeated in 10 years interval, if negative. Both, FOBT+ colonoscopy and screening colonoscopy are considered preventive colonoscopies. FOBT performed in the laboratory is designated as diagnostic FOBT. Interval cancer is defined as a malignity diagnosed after an index exam (preventive, diagnostic, or therapeutic) in which no cancer is detected, and before the date of the next recommended exam.

Aims & Methods

The analysis included men and women of age ≥ 55 diagnosed with their first colorectal cancer in the period 2016-2020 (data source: National Cancer Registry). For those patients, the search of examinations in the National Registry of Reimbursed Health Services was performed focused on procedures in the period 0.5-5.5 years (depending on the type of examination; FOBT till 2.5 years, colonoscopy till 5.5 years) before the time of the cancer diagnosis: FOBT (screening and diagnostic), FOBT+colonoscopy and screening colonoscopy marked as preventive colonoscopy, diagnostic colonoscopy. As therapy, the endoscopic polypectomy, mucosal resection, and submucosal dissection performed within 6 months of the mentioned examinations were considered.

Results

There were colorectal cancers in 30,723 patients found (Table 1), with 13,816 cancers in stages III and IV (45.0%). The majority of the patients (64.4%) did not undergo any observed procedure. 20.3% of patients had negative FOBT, so, they were considered as patients with interval cancer. Preventive colonoscopies were accompanied by a low rate of interval cancers (0.9%).

Conclusion

The highest number of colorectal cancers was found in patients with no procedures related to CRC incidence and mortality reduction (preventive, diagnostic, or therapeutic). Approximately 20% of people with colorectal cancers had interval carcinoma (after negative screening FOBT) which could be caused by the inappropriate setting of FOBT examination or low sensitivity of FOBT. The higher proportion of cancers after negative screening FOBT might be also caused by the fold higher number of procedures FOBT performed.

References

Supported by the Czech Ministry of Health grants NV18-08-00246 and NU22-08-00424 and projects MO1012 and Cooperatio.