Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

Impact of withdrawal time on adenoma detection rate: results from a prospective multicenter trial.

BACKGROUND AND AIMS: Performing a high-quality colonoscopy is critical for optimizing the adenoma detection rate (ADR). Colonoscopy withdrawal time (a surrogate measure) of ≥6 minutes is recommended; however, a threshold of a high-quality withdrawal and its impact on ADR are not known. METHODS: We examined withdrawal time (excluding polyp resection and bowel cleaning time) of subjects undergoing screening and/or surveillance colonoscopy in a prospective, multicenter, randomized controlled trial. We examined the relationship of withdrawal time in 1-minute increments on ADR and reported odds ratio (OR) with 95% confidence intervals. Linear regression analysis was performed to assess the maximal inspection time threshold that impacts the ADR. RESULTS: A total of 1142 subjects (age, 62.3 ± 8.9 years; 80.5% men) underwent screening (45.9%) or surveillance (53.6%) colonoscopy. The screening group had a median withdrawal time of 9.0 minutes (interquartile range [IQR], 3.3) with an ADR of 49.6%, whereas the surveillance group had a median withdrawal time of 9.3 minutes (IQR, 4.3) with an ADR of 63.9%. ADR correspondingly increased for a withdrawal time of 6 minutes to 13 minutes, beyond which ADR did not increase (50.4% vs 76.6%, P < .01). For every 1-minute increase in withdrawal time, there was 6% higher odds of detecting an additional subject with an adenoma (OR, 1.06; 95% confidence interval, 1.02-1.10; P = .004). CONCLUSIONS: Results from this multicenter, randomized controlled trial underscore the importance of a high-quality examination and efforts required to achieve this with an incremental yield in ADR based on withdrawal time. (Clinical trial registration number: NCT03952611.).

High-Definition Colonoscopy Compared With Cuff- and Cap-Assisted Colonoscopy: Results From a Multicenter, Prospective, Randomized Controlled Trial.

BACKGROUND AND AIMS: Mucosal exposure devices including distal attachments such as the cuff and cap have shown variable results in improving adenoma detection rate (ADR) compared with high-definition white light colonoscopy (HDWLE). METHODS: We performed a prospective, multicenter randomized controlled trial in patients undergoing screening or surveillance colonoscopy comparing HDWLE to 2 different types of distal attachments: cuff (CF) (Endocuff Vision) or cap (CP) (Reveal). The primary outcome was ADR. Secondary outcomes included adenomas per colonoscopy, advanced adenoma and sessile serrated lesion detection rate, right-sided ADR, withdrawal time, and adverse events. Continuous variables were compared using Student's t test and categorical variables were compared using chi-square or Fisher's exact test using statistical software Stata version16. A P value <.05 was considered significant. RESULTS: A total of 1203 subjects were randomized to either HDWLE (n = 384; mean 62 years of age; 81.3% males), CF (n = 379; mean 62.7 years of age; 79.9% males) or CP (n = 379; mean age 62.1 years of age; 80.5% males). No significant differences were found among 3 groups for ADR (57.3%, 59.1%, and 55.7%; P = .6), adenomas per colonoscopy (1.4 ± 1.9, 1.6 ± 2.4, and 1.4 ± 2; P = .3), advanced adenoma (7.6%, 9.2%, and 8.2%; P = .7), sessile serrated lesion (6.8%, 6.3%, and 5.5%; P = .8), or right ADR (48.2%, 49.3%, and 46.2%; P = .7). The number of polyps per colonoscopy were significantly higher in the CF group compared with HDWLE and CP group (2.7 ± 3.4, 2.3 ± 2.5, and 2.2 ± 2.3; P = .013). In a multivariable model, after adjusting for age, sex, body mass index, withdrawal time, and Boston Bowel Preparation Scale score, there was no impact of device type on the primary outcome of ADR (P = .77). In screening patients, CF resulted in more neoplasms per colonoscopy (CF: 1.7 ± 2.6, HDWLE: 1.3 ± 1.7, and CP: 1.2 ± 1.8; P = .047) with a shorter withdrawal time. CONCLUSIONS: Results from this multicenter randomized controlled trial do not show any significant benefit of using either distal attachment devices (CF or CP) over HDWLE, at least in high-detector endoscopists. The Endocuff may have an advantage in the screening population. (ClinicalTrials.gov, Number: NCT03952611).

Associations of Habitual Dietary Intake With Fecal Short-Chain Fatty Acids and Bowel Functions in Irritable Bowel Syndrome.

BACKGROUND GOALS: Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). STUDY: In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (rs) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. RESULTS: Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=-0.53; P=0.04) with complete evacuation in IBS-D. Fiber (rs=0.65; P=0.02) and starch (rs=0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=-0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. CONCLUSIONS: Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.

Narrow-band imaging versus white light for the detection of proximal colon serrated lesions: a randomized, controlled trial.

BACKGROUND: The value of narrow-band imaging (NBI) for detecting serrated lesions is unknown. OBJECTIVE: To assess NBI for the detection of proximal colon serrated lesions. DESIGN: Randomized, controlled trial. SETTING: Two academic hospital outpatient units. PATIENTS: Eight hundred outpatients 50 years of age and older with intact colons undergoing routine screening, surveillance, or diagnostic examinations. INTERVENTIONS: Randomization to colon inspection in NBI versus white-light colonoscopy. MAIN OUTCOME MEASUREMENTS: The number of serrated lesions (sessile serrated polyps plus hyperplastic polyps) proximal to the sigmoid colon. RESULTS: The mean inspection times for the whole colon and proximal colon were the same for the NBI and white-light groups. There were 204 proximal colon lesions in the NBI group and 158 in the white light group (P = .085). Detection of conventional adenomas was comparable in the 2 groups. LIMITATIONS: Lack of blinding, endoscopic estimation of polyp location. CONCLUSION: NBI may increase the detection of proximal colon serrated lesions, but the result in this trial did not reach significance. Additional study of this issue is warranted. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01572428.).

Balloon expulsion testing for the diagnosis of dyssynergic defecation in women with chronic constipation.

INTRODUCTION AND HYPOTHESIS: Dyssynergic defecation can be difficult to diagnose. Anorectal manometry and defecography are often used to make this diagnosis. However, these tests are expensive and require expertise. Balloon expulsion testing may be a simple alternative. We compared balloon expulsion to anorectal manometry and defecography for diagnosing dyssynergia in women with chronic constipation. METHODS: We conducted a retrospective review. All women presenting for evaluation of chronic constipation who underwent concurrent balloon testing, manometry, and defecography were included. A diagnosis of dyssynergic defecation was established by either defecography revealing prolonged/incomplete rectal evacuation and/or by manometry revealing paradoxical contraction/inadequate relaxation of the pelvic floor. Inability to expel a 50-ml balloon defined dyssynergic defecation by balloon testing. Sensitivity, specificity, and predictive values were calculated. RESULTS: A total of 61 women met inclusion criteria. Mean age was 50 years. There were 36 women (59 %) who met Rome III criteria for dyssynergic defecation on defecography and/or manometry. Only 12 of these 36 (33 %) were similarly diagnosed by balloon testing. The sensitivity and positive predictive value of balloon testing for dyssynergia were 33 and 71 %, respectively. Of the 25 (41 %) women who did not meet Rome III criteria for dyssynergia on defecography and/or manometry, 20 (80 %) also had negative balloon testing. Thus, the specificity and negative predictive value of balloon testing for diagnosing dyssynergia were 80 and 50 %, respectively. CONCLUSIONS: In our population, balloon expulsion was not an ideal screening test for dyssynergic defecation in women with constipation. Multimodal testing is necessary for more accurate diagnosis.

Microbiota-Short Chain Fatty Acid Relationships and Microbial Substrate Preferences Vary Across the Spectrum of Irritable Bowel Syndrome (IBS).

Objective: Identifying microbial targets in irritable bowel syndrome (IBS) is challenged by dynamic microbiota-metabolite-host interactions. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features were related to IBS symptoms, subtypes, and endophenotypes. Design: We performed an observational study of stool microbial metagenomes, stool SCFA, and IBS traits (stool form, stool bile acids, and colonic transit) in patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and healthy controls. We analyzed associations of microbiome composition with stool SCFA to identify microbe-SCFA relationships that were shared and distinct across groups. We compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by stool characteristics. In IBS-D, we compared stool microbiomes of patients with and without bile acid malabsorption (BAM). Results: Overall stool microbiome composition and abundances of individual taxa differed between groups. Increased abundances of several bacterial species were observed in IBS-D including Dorea sp. CAG:317.. Microbes-SCFA relationships varied across groups after accounting for transit and bile acids. Significant microbe-SCFA were common in IBS-D and several SCFA-producing species were inversely correlated with SCFA. Among participants selected by stool form characteristics, functional profiling demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D with BAM. Conclusion: Microbe-SCFA associations differ across IBS subtypes and traits. Altered substrate preferences offer insights into functional microbiome traits and could be used as novel microbial IBS biomarkers. KEY MESSAGES: What is already known on this topic: The intestinal microbiota and its metabolites (e.g., short chain fatty acids [SCFA]) modulate irritable bowel syndrome (IBS) pathophysiology. What this study adds: We studied microbe-SCFA associations across IBS subtypes and endophenotypes to demonstrate (1) the intestinal microbiome plays distinct roles across IBS subtypes, (2) microbial substrate preferences vary between IBS subtypes and influences stool form, and (3) microbe-SCFA patterns may reveal key taxa that underlie shared and distinct microbial mechanisms across the IBS spectrum. How this study might affect research, practice or policy: Findings demonstrate that structural and functional features of the intestinal microbiome may represent unbiased microbial biomarkers for clinical and mechanistic IBS subtypes. Further study of these putative microbial targets as well as their interactions with diet- and host-specific traits should be pursued to develop individualized microbiome-based approached to IBS management.

Associations of Fecal Short Chain Fatty Acids With Colonic Transit, Fecal Bile Acid, and Food Intake in Irritable Bowel Syndrome.

INTRODUCTION: Short-chain fatty acids (SCFAs) correlate with colonic transit time (CTT) and may influence irritable bowel syndrome (IBS) pathophysiology. However, the clinical significance of fecal SCFAs, relationships between SCFAs and other metabolites (bile acids [BAs]), and real-time diet effects on SCFAs in IBS are uncertain. The aim was to evaluate fecal SCFA associations with IBS phenotype and mechanisms and explore effects of real-time diet. METHODS: We conducted a prospective observational study of fecal SCFA, BAs, and CTT in healthy controls (HCs) and participants with IBS. We compared study end points across groups, analyzed relationships between end points, and evaluated the discriminative ability of SCFAs. Diet effects were explored in participants with dietary data. RESULTS: Among 21 HCs and 43 participants with IBS, fecal SCFAs (total, individual) were inversely correlated with overall (all P < 0.01) and segmental (all P < 0.05) CTT; similar associations were observed within HC and IBS groups. The acetate-to-butyrate ratio correlated with slower overall and left CTT in all and in HCs (both P < 0.01). SCFAs (total, acetate) correlated with BAs (total, % primary) in all participants and in those with IBS with diarrhea. Logistic regression analyses demonstrated associations of acetate with slower transit (odds ratio = 0.988, P = 0.002) and BA diarrhea (BAD; odds ratio = 1.014, P = 0.001). Acetate accurately predicted delayed CTT (area under the receiving operating characteristic curve = 0.84) and BAD (area under the receiver operating characteristic curve = 0.79). Adjusting for diet strengthened correlations of total SCFAs with overall CTT ( R = [-0.46], P = 0.04) and SCFAs with transverse CTT (all P < 0.05). DISCUSSION: Fecal SCFAs correlate with CTT and fecal BAs and reliably exclude delayed CTT and BAD. Accounting for diet strengthens SCFA associations with transit.

Early adverse life events and post-traumatic stress disorder in patients with constipation and suspected disordered defecation.

BACKGROUND: Early adverse life events (EALs) and post-traumatic stress disorder (PTSD) are associated with irritable bowel syndrome (IBS). Disordered defecation (DD) presents with symptoms of IBS or functional constipation (FC) and is associated with psychological distress. However, the role of trauma and stress in chronic constipation is poorly defined. We aimed to examine EALS, PTSD, and psychological symptoms in patients with constipation and suspected DD. METHODS: We conducted a survey study among adults with constipation who completed anorectal manometry (ARM) and balloon expulsion testing (BET). Data were collected on socio-demographics, EALs, PTSD, bowel symptoms, quality of life, and anxiety and depression. We performed comparisons between individuals with normal versus abnormal ARM or BET, subgroup analysis by detailed ARM and BET findings, and latent class analysis using individual EAL domains. KEY RESULTS: Among 712 eligible patients, 69 completed the study. EALs and provisional PTSD were present in 75.4% and 27.5%, respectively; rates did not differ between those with normal versus abnormal ARM or BET. Normal testing was associated with higher rates of specific EAL domains (emotional abuse and mental illness), higher depression scores, and poorer mental component scores in both primary and subgroup comparisons (all p < 0.05). Normal testing was associated with a lower likelihood of high-EAL latent class (p = 0.01) membership. Presence of IBS or FC did not influence associations. CONCLUSIONS & INFERENCES: Early adverse life events and PTSD are prevalent in patients with constipation and suspected DD. Those with normal ARM and BET have higher rates of prior emotional abuse and poorer mental health.

Evaluation of timed barium esophagram after per-oral endoscopic myotomy to predict clinical response.

Background and study aims The aim of this study was to evaluate whether timed barium esophagram within 24 hours post-per-oral endoscopic myotomy (POEM) (TBE-PP) could predict clinical outcomes. Patients and methods This was a single-center retrospective study of prospectively collected data on consecutive patients with ≥ 6-month follow-up who underwent POEM followed by TBE-PP. Esophageal contrast retention 2 minutes after TBE-PP was assessed as Grade 1 (< 10 %), 2 (10 %-49 %), 3 (50 %-89 %) or 4 (> 90 %). Eckardt score, esophagogastroduodenoscopy (EGD), high-resolution manometry (HRM) and function lumen imaging probe (FLIP) of the esophagogastric junction (EGJ) were obtained at baseline. These tests along with pH testing of antisecretory therapy were repeated 6 and 24 months after POEM. Clinical response by Eckardt score ≤ 3, EGJ-distensibility index (EGJ-DI) > 2.8 mm 2 /mm Hg, and integrated relaxation pressure (IRP) < 15 mm Hg and incidence of gastroesophageal reflux disease (GERD) were compared by transit time. Results Of 181 patients (58 % male, mean 53 ±â€Š17 yr), TBE-PP was classified as Grade 1 in 122 (67.4 %), Grade 2 in 41 (22.7 %), Grade 3 in 14 (7.7 %) and Grade 4 in 4 (2.2 %). At 6 months, overall clinical response by ES (91.7 %), IRP (86.6 %), EGJ-DI (95.7 %) and the diagnosis of GERD (68.6 %) was similar between Grade 1 and Grade 2-4 TBE-PP. At 24 months, Grade 1 had a higher frequency of a normal IRP compared to Grades 2-4 (95.7 % vs. 60 %, P  = 0.021) but overall response by ES (91.2 %), EGJ-DI (92.3 %) and the diagnosis of GERD (74.3 %) were similar. Conclusions Contrast emptying rate by esophagram after POEM has limited utility to predict clinical response or risk of post-procedure GERD.

Age and Dyssynergia Subtypes Associated With Normal Sphincter Pressures in Women With Fecal Incontinence.

OBJECTIVES: Fecal incontinence (FI) is frequently associated with low sphincter pressures, sensory abnormalities, and advanced age. Twenty-three percent of patients with FI and 22% of healthy patients demonstrate dyssynergic defecation (DD) on high-resolution anorectal manometry. Overflow incontinence occurs in some DD patients with normal resting and squeeze anal sphincter pressures. Our aim was to identify factors associated with normal sphincter pressures in women with FI. METHODS: We reviewed medical records of 134 women with FI. Patients with normal resting and squeeze anal pressures were compared with those with abnormal pressures using Wilcoxon rank sum test and Fisher exact. Multivariable logistic regression was performed to identify factors associated with normal resting and squeeze anal pressures. RESULTS: Among 134 women, abnormal resting and/or squeeze pressures were identified in 113 and normal pressures were identified in 21. Women with normal sphincter pressures were younger (mean age 52.7 ± 10.8 years vs 59.0 ± 14.0 years, P = 0.036), more often had abnormal defecation indices (100% vs 83.2%, P = 0.043) and higher rectal defecation pressures (30.8 ± 18.8 mm Hg vs 50.8 ± 22.6 mm Hg, P < 0.001). There was an overall association between DD subtype and normal and abnormal sphincter pressure groups (P = 0.021). Dyssynergia subtypes I or III (odds ratio, 7.2; 95% confidence interval, 1.8-28.8) and age younger than 67 years (odds ratio, 8.5; 95% confidence interval, 1.5-48.6) were associated with greater odds of having normal sphincter pressures. CONCLUSIONS: Female FI patients with normal anal sphincter pressures are younger, have higher rectal defecation pressures, and more often have type I or type III DD.

Use of Sacral Nerve Stimulation for the Treatment of Overlapping Constipation and Fecal Incontinence.

BACKGROUND Fecal incontinence and constipation are common gastrointestinal complaints, but rarely occur concurrently. Management of these seemingly paradoxical processes is challenging, as treatment of one symptom may exacerbate the other. CASE REPORT A 51-year-old female with lifelong neurogenic bladder secondary to spina bifida occulta presented with progressive symptoms of daily urge fecal incontinence as well as hard bowel movements associated with straining and a sensation of incomplete evacuation requiring manual disimpaction. Pelvic floor testing showed poor ability to squeeze the anal sphincter, which indicated sphincter weakness as a major contributor to her fecal incontinence symptoms. Additionally, on defecography she was unable to widen her posterior anorectal angle or relax the anal sphincter during defecation consistent with dyssynergic defecation. A sacral nerve stimulator was placed for management of her fecal incontinence. Interestingly, her constipation also dramatically improved with sacral neuromodulation. CONCLUSIONS This unique case highlights the emerging role of sacral nerve stimulation in the treatment of complex pelvic floor dysfunction with improvement in symptoms beyond fecal incontinence in a patient with dyssynergic-type constipation.

The panc 3 score: a rapid and accurate test for predicting severity on presentation in acute pancreatitis.

GOAL: The goal of our study was to develop a simple rule that could rapidly identify those at risk for severe acute pancreatitis (SAP) in the ER. METHODS: We identified all published studies reporting risk factors for SAP. We identified 3 risk factors which had been shown to predict SAP. The risk factors we identified were a serum hematocrit greater than 44 mg/dL, a body mass index (BMI) greater than 30 mg/kg, and a chest x-ray which reveals a pleural effusion (Panc 3 criteria). We computed the test-operating characteristics and likelihood ratios for each risk factor using the patients originally sampled in each of the studies (n=393). For validation, we examined Panc 3's ability to predict SAP in patients seen at our medical center [University of North Carolina at Chapel Hill (UNC) hospitals n=238]. RESULTS: The likelihood ratios positive and negative for HCT, BMI>30 kg/M, and a chest x-ray with a pleural effusion were 14, 9.8, and 8.7, respectively, for the original data and 178, 2.4, and 1.3 for the UNC data. Sensitivity analysis revealed satisfaction of the HCT, BMI, and pleural effusion criteria had a posttest likelihood of disease 99% when the pretest probability of disease varied from 12-25%. These values were true for the original and UNC data. CONCLUSIONS: The Panc 3 score is easy to use and accurate for the prediction of SAP. The serum HCT was the strongest predictor of SAP. The combination of the Panc 3 variables was highly predictive of SAP.