Inhibition of the type IV secretion system from antibiotic-resistant Helicobacter pylori clinical isolates supports the potential of Cagα as an anti-virulence target.

Helicobacter pylori resistance to antibiotics is a growing problem and it increasingly leads to treatment failure. While the bacterium is present worldwide, the severity of clinical outcomes is highly dependent on the geographical origin and genetic characteristics of the strains. One of the major virulence factors identified in H. pylori is the cag pathogenicity island (cagPAI), which encodes a type IV secretion system (T4SS) used to translocate effectors into human cells. Here, we investigated the genetic variability of the cagPAI among 13 antibiotic-resistant H. pylori strains that were isolated from patient biopsies in Québec. Seven of the clinical strains carried the cagPAI, but only four could be readily cultivated under laboratory conditions. We observed variability of the sequences of CagA and CagL proteins that are encoded by the cagPAI. All clinical isolates induce interleukin-8 secretion and morphological changes upon co-incubation with gastric cancer cells and two of them produce extracellular T4SS pili. Finally, we demonstrate that molecule 1G2, a small molecule inhibitor of the Cagα protein from the model strain H. pylori 26695, reduces interleukin-8 secretion in one of the clinical isolates. Co-incubation with 1G2 also inhibits the assembly of T4SS pili, suggesting a mechanism for its action on T4SS function.

Measuring the observer (Hawthorne) effect on adenoma detection rates.

Background and study aims An independent observer can improve procedural quality. We evaluated the impact of the observer (Hawthorne effect) on important quality metrics during colonoscopies. Patients and Methods In a single-center comparative study, consecutive patients undergoing routine screening or diagnostic colonoscopy were prospectively enrolled. In the index group, all procedural steps and quality metrics were observed and documented, and the procedure was video recorded by an independent research assistant. In the reference group, colonoscopies were performed without independent observation. Colonoscopy quality metrics such as polyp, adenoma, serrated lesions, and advanced adenoma detection rates (PDR, ADR, SLDR, AADR) were compared. The probabilities of increased quality metrics were evaluated through regression analyses weighted by the inversed probability of observation during the procedure. Results We included 327 index individuals and 360 referents in the final analyses. The index group had significantly higher PDRs (62.4% vs. 53.1%, P =0.02) and ADRs (39.4% vs. 28.3%, P =0.002) compared with the reference group. The SLDR and AADR were not significantly increased. After adjusting for potential confounders, the ADR and SLDR were 50% (relative risk [RR] 1.51; 95%, CI 1.05-2.17) and more than twofold (RR 2.17; 95%, CI 1.05-4.47) more likely to be higher in the index group than in the reference group. Conclusions The presence of an independent observer documenting colonoscopy quality metrics and video recording the colonoscopy resulted in a significant increase in ADR and other quality metrics. The Hawthorne effect should be considered an alternative strategy to advanced devices to improve colonoscopy quality in practice.

Automated Detection of Anatomical Landmarks During Colonoscopy Using a Deep Learning Model.

Background and aims: Identification and photo-documentation of the ileocecal valve (ICV) and appendiceal orifice (AO) confirm completeness of colonoscopy examinations. We aimed to develop and test a deep convolutional neural network (DCNN) model that can automatically identify ICV and AO, and differentiate these landmarks from normal mucosa and colorectal polyps. Methods: We prospectively collected annotated full-length colonoscopy videos of 318 patients undergoing outpatient colonoscopies. We created three nonoverlapping training, validation, and test data sets with 25,444 unaltered frames extracted from the colonoscopy videos showing four landmarks/image classes (AO, ICV, normal mucosa, and polyps). A DCNN classification model was developed, validated, and tested in separate data sets of images containing the four different landmarks. Results: After training and validation, the DCNN model could identify both AO and ICV in 18 out of 21 patients (85.7%). The accuracy of the model for differentiating AO from normal mucosa, and ICV from normal mucosa were 86.4% (95% CI 84.1% to 88.5%), and 86.4% (95% CI 84.1% to 88.6%), respectively. Furthermore, the accuracy of the model for differentiating polyps from normal mucosa was 88.6% (95% CI 86.6% to 90.3%). Conclusion: This model offers a novel tool to assist endoscopists with automated identification of AO and ICV during colonoscopy. The model can reliably distinguish these anatomical landmarks from normal mucosa and colorectal polyps. It can be implemented into automated colonoscopy report generation, photo-documentation, and quality auditing solutions to improve colonoscopy reporting quality.

Effectiveness of prescribing codes in reducing inappropriate proton pump inhibitors in ambulatory care.

BACKGROUND: Health care deciders are aware of the inappropriate use of proton pump inhibitors (PPIs). To reduce inappropriate prescriptions, the Conseil du Médicament (CdM) issued a practice guideline and the Régie de l'Assurance Maladie du Quebec (RAMQ) asked prescribers to justify its use by writing a specific indication code for their patients to obtain drug coverage. OBJECTIVES: This study aimed to evaluate the effectiveness of the intervention by the RAMQ to reduce inappropriate PPI prescription. METHODS: A cross-sectional quasi-experimental prospective study was performed in an emergency department. Patients aged 18 years or older were included in 2016 to 2017 and 2019 to 2021 in the pre- and postintervention group, respectively. The proportion of patients on PPI without an appropriate indication were identified from patient interviews and chart review. RESULTS: A total of 871 and 1475 patients were recruited in the pre- and postintervention groups. According to the CdM guideline, the proportion of inappropriate PPI prescription was 30.7% (n = 267) in the preintervention group and 49.1% (n = 724) in the postintervention group (P < 0.001). According to the RAMQ criteria, the proportion of inappropriate PPI prescription was of 76.1% (n = 663) and 81.4% (n = 1200) in the pre- and postintervention group, respectively (P < 0.001). CONCLUSION: This study highlights the ineffectiveness of the codes for PPI prescriptions in reducing inappropriate prescriptions. It seems that the obligation to write a code does not lead to a reassessment of PPI indication.

Incomplete resection rates of 4- to 20-mm non-pedunculated colorectal polyps when using wide-field cold snare resection with routine submucosal injection.

Background and study aims Incomplete resection of 4- to 20-mm colorectal polyps occur frequently (> 10 %), putting patients at risk for post-colonoscopy colorectal cancer. We hypothesized that routine use of wide-field cold snare resection with submucosal injection (CSP-SI) might reduce incomplete resection rates (IRRs). Patients and methods Patients aged 45 to 80 years undergoing elective colonoscopies were enrolled in a prospective clinical study. All 4- to 20-mm non-pedunculated polyps were resected using CSP-SI. Post-polypectomy margin biopsies were obtained to determine IRRs through histopathology assessment. The primary outcome was IRR, defined as remnant polyp tissue found on margin biopsies. Secondary outcomes included technical success and complication rates. Results A total of 429 patients (median age 65 years, 47.1 % female, adenoma detection rate 40 %) with 204 non-pedunculated colorectal polyps 4 to 20 mm removed using CSP-SI were included in the final analysis. CSP-SI was technical successful in 97.5 % (199/204) of cases (5 conversion to hot snare polypectomy). IRR for CSP-SI was 3.8 % (7/183) (95 % confidence interval [CI] 2.7 %-5.5 %). IRR was 1.6 % (2/129), 16 % (4/25), and 3.4 % (1/29) for adenomas, serrated lesions, and hyperplastic polyps respectively. IRR was 2.3 % (2/87), 6.3 % (4/64), 4.0 % (6/151), and 3.1 % (1/32) for polyps 4 to 5 mm, 6 to 9 mm, < 10 mm, and 10 to 20 mm, respectively. There were no CSP-SI-related serious adverse events. Conclusions Use of CSP-SI results in lower IRRs compared to what has previously been reported in the literature for hot or cold snare polypectomy when not using wide-field cold snare resection with submucosal injection. CSP-SI showed an excellent safety and efficacy profile, however comparative studies to CSP without SI are required to confirm these results.

Rates of synchronous advanced neoplasia and colorectal cancer in patients with colonic serrated lesions.

BACKGROUND AND AIMS: Serrated lesions (SL) have been associated with significant risks of developing colorectal cancer (CRC). Data on synchronous findings after SL detection during colonoscopy is limited. Study aim was to evaluate the rate of synchronous advanced neoplasia (S-AN) and synchronous CRC (S-CRC) in colonoscopies where SLs were detected. METHODS: We conducted a retrospective study of screening aged patients 45-74year with colorectal SL (sessile serrated polyp [SSP] or traditional serrated adenoma [TSA]) detected during an elective colonoscopy. Primary outcome was risk of S-AN in patients with SL. Secondary outcomes included risk of S-AN or S-CRC stratified by SL characteristics. RESULTS: The study included 1262 patients with 1649 SLs (1214 with SSPs and 48 with TSAs). 47.2% were female and 22.9% of exams were screening colonoscopies, 48.2% surveillance, 28.9% diagnostic. The overall rates of S-AN and S-CRC were 15.1% and 1.3%, respectively. Presence of SSPs ≥ 10 mm was associated with higher rates of S-AN, (18.1 vs. 12.2%, Odds-Ratio [OR] = 1.61 [95% Confidence Interval [CI] 1.17-2.23], p = 0.004). SSP dysplasia was predictive of S-AN, (30.3 vs 14.1%, OR = 2.68 [95%CI 1.24-5.78], p = 0.012) but not S-CRC. SSP number (≥ 3) and location (proximal) were not predictors of S-AN or S-CRC. CONCLUSION: Patients with SLs are at high-risk of S-AN and S-CRC. Findings of SSPs ≥ 10 mm and SSP dysplasia are associated with high-risk of S-AN. Endoscopists should exercise heightened vigilance for synchronous findings when SLs are detected, especially SSPs ≥ 10 mm or when bowel preparation is suboptimal. Studies contrasting synchronous risk of other polyp types are needed to confirm these results.

Risk of total metachronous advanced neoplasia at surveillance colonoscopy after detection of serrated lesions: a matched case-cohort study.

BACKGROUND : Serrated lesions are potential colorectal cancer precursors. This study evaluated the presence of total metachronous advanced neoplasia (T-MAN) at follow-up in patients with index serrated lesions compared with a matched cohort without serrated lesions. METHODS : Patients aged 45-74 years with serrated lesions were matched 2:1 by sex, age, synchronous polyps, and timing of index colonoscopy, to patients without serrated lesions. The primary outcome was T-MAN (advanced adenoma or high-risk serrated lesion) at follow-up. Secondary outcomes included presence of T-MAN stratified by synchronous polyps and serrated lesion characteristics. RESULTS : 1425 patients were included (475 patients, 642 serrated lesions; 950 controls; median follow-up 2.9 versus 3.6 years). Patients with serrated lesions had greater risk of T-MAN than those without (hazard ratio [HR] 6.1, 95 %CI 3.9-9.6). Patients with serrated lesions and high-risk adenoma (HRA) had higher risk of T-MAN than those with HRA alone (HR 2.6, 95 %CI 1.4-4.7); similarly, patients with serrated lesions plus low-risk adenoma (LRA) had higher risk than those with LRA alone (HR 7.0, 95 %CI 2.8-18.4), as did patients with serrated lesions without adenoma compared with no adenoma (HR 14.9, 95 %CI 6.5-34.0). Presence of proximal sessile serrated lesion (SSL; HR 9.3, 95 %CI 5.4-15.9), large SSL (HR 17.8, 95 %CI 7.4-43.3), and proximal large SSL (HR 25.0, 95 %CI 8.8-71.3), but not distal SSL, were associated with greater risk for T-MAN. CONCLUSION : Patients with serrated lesions had higher risk for T-MAN regardless of synchronous adenomas. Patients with serrated lesions and HRA, and those with large or proximal SSLs, were at greatest risk.

Incomplete resection of colorectal polyps of 4-20 mm in size when using a cold snare, and its associated factors.

BACKGROUND : Cold snare polypectomy (CSP) is increasingly used for polypectomy and is recommended as the first-line modality for small (< 10 mm) polyps. This study aimed to evaluate incomplete resection rates (IRRs) when using CSP for colorectal polyps of 4-20 mm. METHODS : Adults (45-80 years) undergoing screening, surveillance, or diagnostic colonoscopy and CSP by one of nine endoscopists were included. The primary outcome was the IRR for colorectal polyps of 4-20 mm, defined as the presence of polyp tissue in marginal biopsies after resection of serrated polyps or adenomas. Secondary outcomes included the IRR for serrated polyps, ease of resection, and complications. RESULTS: 413 patients were included (mean age 63; 48 % women) and 182 polyps sized 4-20 mm were detected and removed by CSP. CSP required conversion to hot snare resection in < 1 % of polyps of < 10 mm and 44 % of polyps sized 10-20 mm. The IRRs for polyps < 10 mm and ≥ 10 mm were 18 % and 21 %. The IRR was higher for serrated polyps (26 %) compared with adenomas (16 %). The IRR was higher for flat (IIa) polyps (odds ratio [OR] 2.9, 95 %CI 1.1-7.4); and when resection was judged as difficult (OR 4.2, 95 %CI 1.5-12.1), piecemeal resection was performed (OR 6.6, 95 %CI 2.0-22.0), or visible residual polyp was present after the initial resection (OR 5.4, 95 %CI 2.0-14.9). Polyp location, use of a dedicated cold snare, and submucosal injection were not associated with incomplete resection. Intraprocedural bleeding requiring endoscopic intervention occurred in 4.7 %. CONCLUSIONS : CSP for polyps of 4-9 mm is safe and feasible; however, for lesions ≥ 10 mm, CSP failure occurs frequently, and the IRR remains high even after technical success. Incomplete resection was associated with flat polyps, visual residual polyp, piecemeal resection, and difficult polypectomies.

Helicobacter pylori serology is associated with worse overall survival in patients with melanoma treated with immune checkpoint inhibitors.

The microbiome is now regarded as one of the hallmarks of cancer and several strategies to modify the gut microbiota to improve immune checkpoint inhibitor (ICI) activity are being evaluated in clinical trials. Preliminary data regarding the upper gastro-intestinal microbiota indicated that Helicobacter pylori seropositivity was associated with a negative prognosis in patients amenable to ICI. In 97 patients with advanced melanoma treated with ICI, we assessed the impact of H. pylori on outcomes and microbiome composition. We performed H. pylori serology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were H. pylori positive (Pos). H. pylori Pos patients had a significantly shorter overall survival (p = .02) compared to H. pylori negative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in H. pylori Pos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the H. pylori groups. At the taxa level, Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques, and Dorea formicigenerans were increased in the H. pylori Pos group, while Alistipes finegoldii, Hungatella hathewayi and Blautia producta were over-represented in the H. pylori Neg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and Bacteroides xylanisolvens was increased in H. pylori Neg patients. Our results demonstrated that the negative impact of H. pylori on outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate H. pylori in immuno-oncology arena.

Non-optical polyp-based resect and discard strategy: A prospective clinical study.

BACKGROUND: Post-polypectomy surveillance intervals are currently determined based on pathology results. AIM: To evaluate a polyp-based resect and discard model that assigns surveillance intervals based solely on polyp number and size. METHODS: Patients undergoing elective colonoscopies at the Montreal University Medical Center were enrolled prospectively. The polyp-based strategy was used to assign the next surveillance interval using polyp size and number. Surveillance intervals were also assigned using optical diagnosis for small polyps (< 10 mm). The primary outcome was surveillance interval agreement between the polyp-based model, optical diagnosis, and the pathology-based reference standard using the 2020 United States Multi-Society Task Force guidelines. Secondary outcomes included the proportion of reduction in required histopathology evaluations and proportion of immediate post-colonoscopy recommendations provided to patients. RESULTS: Of 944 patients (mean age 62.6 years, 49.3% male, 933 polyps) were enrolled. The surveillance interval agreement for the polyp-based strategy was 98.0% [95% confidence interval (CI): 0.97-0.99] compared with pathology-based assignment. Optical diagnosis-based intervals achieved 95.8% (95%CI: 0.94-0.97) agreement with pathology. When using the polyp-based strategy and optical diagnosis, the need for pathology assessment was reduced by 87.8% and 70.6%, respectively. The polyp-based strategy provided 93.7% of patients with immediate surveillance interval recommendations vs 76.1% for optical diagnosis. CONCLUSION: The polyp-based strategy achieved almost perfect surveillance interval agreement compared with pathology-based assignments, significantly reduced the number of required pathology evaluations, and provided most patients with immediate surveillance interval recommendations.

What size cutoff level should be used to implement optical polyp diagnosis?

BACKGROUND : The risk of advanced pathology increases with polyp size, as does the potential for mismanagement when optical diagnosis is used. This study aimed to evaluate the proportion of patients who would be assigned inadequate surveillance intervals when different size cutoffs are adopted for use of optical diagnosis. METHODS : In a post hoc analysis of three prospective studies, the use of optical diagnosis was evaluated for three polyp size groups: 1-3, 1-5, and 1-10 mm. The primary outcome was the proportion of patients in whom advanced adenomas were found and optical diagnosis resulted in delayed surveillance. Secondary outcomes included agreements between surveillance intervals based on high confidence optical diagnosis and pathology outcomes, reduction in histopathological examinations, and proportion of patients who could receive an immediate surveillance recommendation. RESULTS : We included 3374 patients (7291 polyps ≤ 10 mm) undergoing complete colonoscopies (median age 66.0 years, 75.2 % male, 29.6 % for screening). The percentage of patients with advanced adenomas and either 2- or 7-year delayed surveillance intervals (n = 79) was 3.8 %, 15.2 %, and 25.3 % for size cutoffs of 1-3, 1-5, and 1-10 mm polyps, respectively (P < 0.001). Surveillance interval agreements between pathology and optical diagnosis for the three groups were 97.2 %, 95.5 %, and 94.2 %, respectively. Total reductions in pathology examinations for the three groups were 33.5 %, 62.3 %, and 78.2 %, respectively. CONCLUSION : A 3-mm cutoff for clinical implementation of optical diagnosis resulted in a very low risk of delayed management of advanced neoplasia while showing high surveillance interval agreement with pathology and a one-third reduction in overall requirement for pathology examinations.

Investigation of Fusobacterium Nucleatum in saliva and colorectal mucosa: a pilot study.

As evidence has been linking the oral bacterium Fusobacterium nucleatum (F. nucleatum) to colorectal tumorigenesis, we aimed to produce preliminary data on the expression of F. nucleatum in both oral and colorectal body sites in cases diagnosed with colorectal neoplasms (CRN) and CRN-free controls. We conducted a pilot hospital-based case-control study among patients who underwent colonoscopy examination. Saliva samples and biopsies from healthy colon mucosa from CRN cases and CRN-free controls, and from tumors in cases, were collected, as well as data on periodontal condition and potential CRN risk factors. A total of 22 CRN cases and 21 CRN-free controls participated in this study, with a total of 135 biospecimens collected and analyzed by qPCR for detection and quantification of F. nucleatum. The detection rate of F. nucleatum was 95% in saliva samples and 18% in colorectal mucosa specimens. The median (95% CI) salivary F. nucleatum level was 0.35 (0.15-0.82) and 0.12 (0.05-0.65) in case and control groups, respectively, with a Spearman correlation of 0.64 (95% CI 0.2-0.94) between F. nucleatum level in saliva and healthy colorectal mucosa in controls. Our study results support the need for and the feasibility of further studies that aim to investigate the association between oral and colorectal levels of F. nucleatum in CRN cases and controls.Clinical Relevance: Considering the current evidence linking F. nucleatum to colorectal carcinogenesis, investigating the role of oral F. nucleatum expression in its colorectal enrichment is crucial for colorectal cancer screening and prevention avenues.

Evaluation of the polyp-based resect and discard strategy: a retrospective study.

BACKGROUND: Standard colonoscopy practice requires removal and histological characterization of almost all detected small (< 10 mm) and diminutive (≤ 5 mm) colorectal polyps. This study aimed to test a simplified polyp-based resect and discard (PBRD) strategy that assigns surveillance intervals based only on size and number of small/diminutive polyps, without the need for pathology examination. METHODS: A post hoc analysis was performed on patients enrolled in a prospective study. The primary outcome was surveillance interval agreement of the PBRD strategy with pathology-based management according to 2020 US Multi-Society Task Force guidelines. Chart analysis also evaluated clinician adherence to pathology-based recommendations. One-sided testing was performed with a null-hypothesis of 90 % agreement with pathology-based surveillance intervals and a two-sided 96.7 % confidence interval (CI) using correction for multiple testing. RESULTS: 452 patients were included in the study. Surveillance intervals assigned using the PBRD strategy were correct in 97.8 % (96.7 %CI 96.3-99.3 %) of patients compared with pathology-based management. The PBRD strategy reduced pathology examinations by 58.7 % while providing 87.8 % of patients with immediate surveillance interval recommendations on the day of colonoscopy, compared with 47.1 % when using pathology-based management. Chart analysis of surveillance interval assignments showed 63.3 % adherence to pathology-based guidelines. CONCLUSION: The PBRD strategy surpassed the 90 % agreement with the pathology-based standard for determining surveillance interval, reduced the need for pathology examinations, and increased the proportion of patients receiving immediate surveillance interval recommendations. The PBRD strategy does not require expertise in optical diagnosis and may replace histological characterization of small and diminutive colorectal polyps.

A Multicenter Randomized Controlled Trial Comparing Two Bowel Cleansing Regimens for Colonoscopy After Failed Bowel Preparation.

BACKGROUND & AIMS: Failed bowel preparation for colonoscopy occurs commonly, but the optimal regimen for the subsequent attempt is unknown. High-volume preparations often are used but are not well studied. The objective of this study was to compare the efficacy, tolerability, and safety of 2 regimens for use after failed bowel preparation. METHODS: A multicenter, endoscopist-blinded randomized controlled trial was conducted in patients who previously failed bowel preparation despite adequate compliance. Patients were randomized to 1 of 2 split polyethylene glycol (PEG) regimens, preceded by 15 mg bisacodyl: PEG 2 L the evening before and 2 L the day of colonoscopy (PEG 2+2L+bisacodyl), or 4 L and 2 L (PEG 4+2L+bisacodyl). All patients followed a low-fiber diet on both the third and second day before the procedure, followed by a clear fluid diet the day before and the morning of the colonoscopy. The primary outcome was adequate bowel preparation, defined as a Boston Bowel Preparation Scale total score of 6 or higher, with all segment scores of 2 or higher. Secondary outcomes included adenoma detection rate, advanced adenoma detection rate, sessile serrated lesion detection, cecal intubation rate, tolerability, and adverse events. RESULTS: A total of 196 subjects were randomized at 4 academic centers in Canada (mean age, 60.7 y; SD, 11.4 y; 44.9% were women). There were no significant differences between the PEG 2+2L+bisacodyl and the PEG 4+2L+bisacodyl groups in achieving adequate bowel preparation (91.2% vs 87.6%; P = .44). There were no significant differences with regard to mean adenoma detection rate (37.4% vs 31.5%; P = .41), advanced adenoma detection rate (18.7% vs 11.2%; P = .16), sessile serrated lesion detection (8.8% vs 5.6%; P = .41), and cecal intubation rate (96.7% vs 92.1%; P = .19). The 2 regimens were similarly well tolerated, but PEG 2+2L+bisacodyl was associated with a higher willingness to repeat the bowel preparation (91.2% vs 66.2%; P < .001). CONCLUSIONS: Split-dose 4 L-PEG with 15 mg bisacodyl, along with dietary restrictions, has similar efficacy as a higher-volume preparation, and should be considered for patients who previously failed bowel preparation (ClinicalTrials.gov number, NCT02976805).

The location-based resect and discard strategy for diminutive colorectal polyps: a prospective clinical study.

BACKGROUND: Clinical implementation of the resect-and-discard strategy has been difficult because optical diagnosis is highly operator dependent. This prospective study aimed to evaluate a resect-and-discard strategy that is not operator dependent. METHODS: The study evaluated a resect-and-discard strategy that uses the anatomical polyp location to classify colonic polyps into non-neoplastic or low risk neoplastic. All rectosigmoid diminutive polyps were considered hyperplastic and all polyps located proximally to the sigmoid colon were considered neoplastic. Surveillance interval assignments based on these a priori assumptions were compared with those based on actual pathology results and on optical diagnosis. The primary outcome was ≥ 90 % agreement with pathology in surveillance interval assignment. RESULTS: 1117 patients undergoing complete colonoscopy were included and 482 (43.1 %) had at least one diminutive polyp. Surveillance interval agreement between the location-based strategy and pathological findings using the 2020 US Multi-Society Task Force guideline was 97.0 % (95 % confidence interval [CI] 0.96-0.98), surpassing the ≥ 90 % benchmark. Optical diagnoses using the NICE and Sano classifications reached 89.1 % and 90.01 % agreement, respectively (P < 0.001), and were inferior to the location-based strategy. The location-based resect-and-discard strategy allowed a 69.7 % (95 %CI 0.67-0.72) reduction in pathology examinations compared with 55.3 % (95 %CI 0.52-0.58; NICE and Sano) and 41.9 % (95 %CI 0.39-0.45; WASP) with optical diagnosis. CONCLUSION: The location-based resect-and-discard strategy achieved very high surveillance interval agreement with pathology-based surveillance interval assignment, surpassing the ≥ 90 % benchmark and outperforming optical diagnosis in surveillance interval agreement and the number of pathology examinations avoided.

Do Age and Sex Influence Anorectal Manometry Parameters?

BACKGROUND: High-resolution anorectal manometry (HRM) is widely used in the evaluation of anal incontinence and constipation, which become increasingly prevalent with age. However, the impact of age and comorbidities on physiological digestive parameters remains poorly understood. In this study, we aimed to evaluate the effect of age on anorectal function. METHODS: We conducted a retrospective study on patients at our digestive motility clinic between January 2016 and May 2019. All patients with a normal HRM were included. Clinical data and HRM parameters were collected in a database. Multivariate regression analyses were performed to evaluate the effects of age, sex, medical comorbidities and obstetric history on anorectal HRM parameters. KEY RESULTS: One hundred and forty-four patients were included (mean age: 53 ± 16 years, 72% females). The main indications for anorectal HRM were incontinence (44%), constipation (37%) and anorectal pain (9%). Age was significantly associated with higher maximum tolerable volume (ß = +0.48 mL year-1, P = 0.04) and higher rectal compliance (ß = +0.04 mL year-1, P = 0.01). Independently from age and medical comorbidities, female demonstrated significantly lower mean endurance squeeze pressure (ß = -44.4 mmHg, P < 0.001), maximal squeeze pressure (ß = -62.3 mmHg; P < 0.001), volume at first urge (ß = -16.7 mL, P = 0.02) and maximum tolerable volume (ß = -16.1 mL, P = 0.046). Vaginal birth was associated with lower tolerable maximum pressure (ß = -39.4 mmHg, P = 0.046). CONCLUSION: Age and sex are independent factors which influence anorectal HRM parameters. These findings should be taken into consideration when interpreting anorectal HRM.

Effects of Age on Esophageal Motility: A High-Resolution Manometry Study.

BACKGROUND: Studies have found possible physiologic changes to esophageal motility with aging currently not taken into account in routine high-resolution manometry (HRM) interpretation. We aimed to quantify the relationship between these physiologic changes and aging to improve HRM interpretation. METHODS: We conducted a retrospective analysis of patients who underwent HRM at a tertiary hospital center between 2015 and 2019. Inclusion criteria were patients aged ≥18 years with normal HRM. Exclusion criteria were abnormal HRM, abnormal upper digestive endoscopy or imagery. Outcomes were median integrated relaxation pressure (IRP), lower esophageal sphincter (LES) pressure, distal contractal integral (DCI), distal latency (DL), and peristaltic break (PB) according to the v4.0 Chicago classification criteria. Effect of age was examined through univariate and multivariate linear regression analysis. RESULTS: We identified 1,917 patients with HRM and included 722 patients with normal exams (median age 56 years (interquartile range (IQR) 46 - 66), 63.8% female). Indications for HRM included dysphagia (39.6%), gastroesophageal reflux disease (29.5%), and chest pain (11.5%). There was statistically significant relationship between age and IRP (r = 0.20, P < 0.0001) as well as DCI (r = 0.12, P = 0.001) and DL (r = -0.09, P = 0.02). No statistically significant relationship was found between age and LES pressure or PB. CONCLUSION: We found that IRP, DCI, and to a lesser extent, DL, are significantly correlated with the normal aging process in symptomatic patients. These findings should be taken into consideration when interpreting esophageal HRM.

Clinical validation of the SIMPLE classification for optical diagnosis of colorectal polyps.

Background and study aims A novel endoscopic optical diagnosis classification system (SIMPLE) has recently been developed. This study aimed to evaluate the SIMPLE classification in a clinical cohort. Patients and methods All diminutive and small colorectal polyps found in a cohort of individuals undergoing screening, diagnostic, or surveillance colonoscopies underwent optical diagnosis using image-enhanced endoscopy (IEE) and the SIMPLE classification. The primary outcome was the agreement of surveillance intervals determined by optical diagnosis compared with pathology-based results for diminutive polyps. Secondary outcomes included the negative predictive value (NPV) for rectosigmoid adenomas, the percentage of pathology exams avoided, and the percentage of immediate surveillance interval recommendations. Analysis of optical diagnosis for polyps ≤ 10 mm was also performed. Results 399 patients (median age 62.6 years; 55.6 % female) were enrolled. For patients with at least one polyp ≤ 5 mm undergoing optical diagnosis, agreement with pathology-based surveillance intervals was 93.5 % (95 % confidence interval [CI] 91.4-95.6). The NPV for rectosigmoid adenomas was 86.7 % (95 %CI 77.5-93.2). When using optical diagnosis, pathology analysis could be avoided in 61.5 % (95 %CI 56.9-66.2) of diminutive polyps, and post-colonoscopy surveillance intervals could be given immediately to 70.9 % (95 %CI 66.5-75.4) of patients. For patients with at least one ≤ 10 mm polyp, agreement with pathology-based surveillance intervals was 92.7 % (95 %CI 89.7-95.1). NPV for rectosigmoid adenomas ≤ 10 mm was 85.1 % (95 %CI CI 76.3-91.6). Conclusions IEE with the SIMPLE classification achieved the quality benchmark for the resect and discard strategy; however, the NPV for rectosigmoid polyps requires improvement.

Lidocaine before esophageal manometry and ambulatory pH monitoring: A randomized controlled trial.

BACKGROUND: Lidocaine is commonly applied to improve the tolerance of esophageal manometry (EM) and ambulatory pH monitoring (PM). We recently published data suggesting a benefit to this practice and we aimed to confirm these findings in a randomized trial. METHODS: We conducted a double-blind, randomized trial of lidocaine nasal spray versus placebo (saline) before EM and PM. Patients referred to our center who met inclusion criteria were enrolled. Patients were asked to fill a questionnaire after their test and patient-reported adverse effects were compared. KEY RESULTS: Three hundred and four patients were enrolled in our trial. Lidocaine and placebo groups were demographically similar. The primary outcome, pain during catheter insertion, occurred in 60/148 (40.5%) patients in the lidocaine group versus in 72/152 (47.4%) patients in the placebo group (OR: 0.76 [95% CI: 0.48-1.20]; p = 0.23). Patients receiving lidocaine were less likely to report nausea during test recording (OR: 0.48 [95% CI: 0.24-0.91]; p = 0.02) and reported slightly lower intensity of pain during both catheter insertion and test recording (4.68 ± 2.06 versus 5.41 ± 2.24 on 10; p = 0.048 and 3.71 ± 2.00 versus 4.93 ± 2.55 on 10; p = 0.03, respectively). Furthermore, patients receiving lidocaine were less likely to report their test as globally uncomfortable and painful (57% vs. 75%; p = 0.003 and 14% vs. 21%; p = 0.02, respectively). No events of systemic lidocaine toxicity occurred during the study period. CONCLUSIONS: Routine use of lidocaine before esophageal function tests does not reduce pain during catheter insertion but may provide other modest benefits with limited toxicity.

Prevalence of Celiac Disease in Patients with Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) frequently coexists with other autoimmune diseases, including celiac disease (CeD). Although the prevalence of CeD is high among cohorts with PBC, few studies have directly compared this prevalence to those among individuals with other liver diseases (OLD). AIM: To compare the prevalence of CeD between a cohort with PBC and a cohort with OLD. METHODS: Retrospective study from January 2013 to December 2016. All consecutive patients with an anti-transglutaminase (tTG) assay requested by a hepatologist and a diagnosis of chronic liver disease were included. CeD diagnosis was confirmed by duodenal biopsies. RESULTS: We included 399 consecutive patients (53.1 years SD 14.0, 54.1% women), notably 51 individuals with PBC and 348 individuals with OLD. PBC group included significantly more women (90.2% versus 48.9% P < 0.0001). The prevalence of CeD was higher in the group with PBC compared to the group with OLD (11.8 versus 2.9%, P < 0.003). In the OLD group, the prevalence of CeD was comparable regardless of the etiologic subgroup (nonalcoholic steatohepatitis 2.7% versus alcoholic liver disease 4.3%, versus viral 1.5% versus other autoimmune liver diseases 3.3%, NS). The presence of gastrointestinal symptoms at the time of the tTG assay was comparable between PBC and OLD groups (31.4 versus 29.6%, NS). CONCLUSION: There is a higher prevalence of CeD in the PBC group compared to other liver diseases.