Clinical outcomes of peroral endoscopic myotomy with and without septotomy for management of epiphrenic diverticula: an international multicenter experience.

BACKGROUND AND AIMS: There are few data favoring the need for septotomy at the time of peroral endoscopic myotomy (POEM) or if POEM alone is sufficient. Our aim was to compare POEM outcomes with and without septotomy (POEM+S or POEM-S) in patients with symptomatic epiphrenic diverticula (ED) and an underlying motility disorder. METHODS: This was an international, multicenter retrospective study involving 21 centers between January 2014 and January 2023. Patients with ED and an underlying motility disorder who underwent POEM were included. The primary outcome was clinical success (Eckardt score [ES] ≤3 or a 1-point drop in ES for patients with baseline ES <3) without the need for repeat surgical/endoscopic interventions during follow-up. RESULTS: A total of 85 patients (mean age, 64.29 ± 17.1 years; 32 [37.6%] female) with ED and underlying motility disorder underwent POEM+S (n = 47) or POEM-S (n = 38). Patients in the POEM+S group had a significantly higher mean pre-POEM ES (7.3 ± 2.1 vs 5.8 ± 2; P = .002). The most common indication for POEM was achalasia (51% in the POEM+S cohort and 51.8% in the POEM-S cohort; P = .7). A posterior approach was favored in the POEM+S group (76.6% vs 52.6%; P = .02). A similar rate of technical success was seen in both groups (97.9% vs 100%; P = .1). The rate of adverse events was similar between the 2 cohorts (4.2% vs 8.1%; P = .6). The median length of hospital stay after POEM-S was significantly longer compared with POEM+S (2 days [interquartile range (IQR), 1-4 days] vs 1 day [IQR, 1-2 days]; P = .005). Clinical success was equivalent between the 2 groups (83% vs 86.8%; P = .6) at a median follow-up duration of 8 months (IQR, 3-19 months). CONCLUSIONS: In patients with ED and an underlying motility disorder, both POEM+S and POEM-S are equally safe and effective, with similar procedure duration and a low recurrence rate at short-term follow-up. Future comparative prospective studies with long-term follow-up are required to validate these findings.

Effect of computer-aided colonoscopy on adenoma miss rates and polyp detection: A systematic review and meta-analysis.

BACKGROUND AND AIM: Multiple computer-aided techniques utilizing artificial intelligence (AI) have been created to improve the detection of polyps during colonoscopy and thereby reduce the incidence of colorectal cancer. While adenoma detection rates (ADR) and polyp detection rates (PDR) are important colonoscopy quality indicators, adenoma miss rates (AMR) may better quantify missed lesions, which can ultimately lead to interval colorectal cancer. The purpose of this systematic review and meta-analysis was to determine the efficacy of computer-aided colonoscopy (CAC) with respect to AMR, ADR, and PDR in randomized controlled trials. METHODS: A comprehensive, systematic literature search was performed across multiple databases in September of 2022 to identify randomized, controlled trials that compared CAC with traditional colonoscopy. Primary outcomes were AMR, ADR, and PDR. RESULTS: Fourteen studies totaling 10 928 patients were included in the final analysis. There was a 65% reduction in the adenoma miss rate with CAC (OR, 0.35; 95% CI, 0.25-0.49, P < 0.001, I2  = 50%). There was a 78% reduction in the sessile serrated lesion miss rate with CAC (OR, 0.22; 95% CI, 0.08-0.65, P < 0.01, I2  = 0%). There was a 52% increase in ADR in the CAC group compared with the control group (OR, 1.52; 95% CI, 1.39-1.67, P = 0.04, I2  = 47%). There was 93% increase in the number of adenomas > 10 mm detected per colonoscopy with CAC (OR 1.93; 95% CI, 1.18-3.16, P < 0.01, I2  = 0%). CONCLUSIONS: The results of the present study demonstrate the promise of CAC in improving AMR, ADR, PDR across a spectrum of size and morphological lesion characteristics.

Association between baseline hyperplastic polyps and metachronous serrated lesions.

BACKGROUND AND AIMS: Some data suggest that individuals with numerous, <10-mm, rectosigmoid hyperplastic polyps (HPs) are at average risk for the development of metachronous advanced adenomatous neoplasia. Guidelines suggest that these individuals do not need surveillance colonoscopy and should be followed akin to individuals with a normal colonoscopy. Less is known of the risk of metachronous neoplasia because of ≥1 HPs <10 mm proximal to the sigmoid colon. We compared the risk of metachronous neoplasia between individuals with small HPs and those with normal colonoscopy, specifically addressing the impact of location and number of HPs on risk. METHODS: Colonoscopy and pathology reports from patients with ≥2 colonoscopies between 2004 and 2014 were reviewed. Exclusions included inpatients; age <40 or >75 years; and family or personal history of colorectal cancer, inflammatory bowel disease, previous colorectal surgery, or a previous colonoscopy with any adenoma, sessile serrated lesion (SSL), or HP ≥10 mm. The risk of metachronous neoplasia, including adenomas and SSLs, was compared in individuals with a normal index colonoscopy and those with <10-mm HPs stratified by location and number of HPs. RESULTS: After exclusion, 1795 patients were included. At index colonoscopy, 82% (n = 1469) had a normal examination, 12% (219) had only 1, and 6% (107) had between 2 and 9 HPs <10 mm. Compared with patients with a normal index colonoscopy, patients with a proximal (odds ratio, 3.82; 95% confidence interval, 1.77-7.53) or distal HP (odds ratio, 2.23; 95% confidence interval, 1.18-4.00) had an increased risk of metachronous SSLs but not adenomas. CONCLUSIONS: Patients with small proximal and distal HPs are at increased risk of metachronous SSLs. These preliminary findings warrant consideration during surveillance recommendations and future studies in larger cohorts.

Web-Based Model for Predicting Time to Surgery in Young Patients with Familial Adenomatous Polyposis: An Internally Validated Study.

INTRODUCTION: The timing of prophylactic colorectal surgery in patients with familial adenomatous polyposis (FAP) is based on the immediacy of the colorectal cancer risk. The ability to predict the need for surgery may help patients and their families plan in the context of life events and CRC risk. We created a model to predict the likelihood of surgery within 2 and 5 years of first colonoscopy at our institution. METHODS: A single institution hereditary colorectal syndrome (Cologene™) database was interrogated for all patients with FAP having a deleterious APC mutation. Patients with first colonoscopy after age 30 and before year 2000 were excluded. Cox regression analysis was done to assess multiple factors associated with surgery, followed by stepwise Cox regression analysis to select an optimal model. Receiver operator curve (ROC) analysis was performed to assess the model. RESULTS: A total of 211 (53% female) patients were included. Forty-five percent underwent surgery after an average of 3.8 years of surveillance. The final model was created based on initial clinical characteristics (age, gender, BMI, family history of desmoids, genotype-phenotype correlation), initial colonoscopic characteristics (number of polyps, polyp size, presence of high-grade dysplasia); and on clinical events (chemoprevention and polypectomy). AUC was 0.87 and 0.84 to predict surgery within 2 and 5 years, respectively. The final model can be accessed at this website: http://app.calculoid.com/#/calculator/29638 . CONCLUSION: This web-based tool allows clinicians to stratify patients' likelihood of colorectal surgery within 2 and 5 years of their initial examination, based on clinical and endoscopic features, and using the philosophy of care guiding practice at this institution.

Natural history of colonic polyposis in young patients with familial adenomatous polyposis.

BACKGROUND AND AIMS: Proctocolectomy prevents colorectal cancer in familial adenomatous polyposis (FAP). Colorectal polyp progression is one of the indications for surgery. No data exist regarding the natural history of colorectal polyposis in young patients with FAP. This study examined the rate of polyposis progression and factors associated with it. METHODS: Patients with FAP <30 years old who had undergone ≥2 colonoscopies since 2000 were identified. Rate of polyposis progression was calculated by review of polyp counts obtained from baseline and last colonoscopy, accounting for any polyps removed during the observation period. Endoscopic and non-endoscopic factors affecting the rate of polyposis progression were evaluated. Multivariate analysis was performed to identify factors associated with rate of polyposis progression. RESULTS: One hundred sixty-eight patients (52% female; median age, 13.5 years) were included. Median rate of polyposis progression was 25.4 polyps/year (interquartile range, 9.5-69.8). Highest median rate of polyposis progression (89 polyps/year) was associated with mutation in codon 1309. The rate of polyposis progression was independently associated with the location of mutation in the adenomatous polyposis coli gene, the number of polyps at the initial colonoscopy, and exposure to chemoprevention. Of the 39.9% of patients who underwent surgery, an increase in polyp number was the most common indication (53.7%). CONCLUSIONS: The rate of polyposis progression in young patients with FAP varies with a median of about 25 new polyps per year. Progression is associated with distinct factors, which can be used in discussion with patients regarding the need for and timing of prophylactic colorectal surgery.

Hybrid argon plasma coagulation in Barrett's esophagus: a systematic review and meta-analysis.

BACKGROUND/AIMS: Patients with Barrett's esophagus are at increased risk of developing esophageal adenocarcinoma. Endoscopic therapies aim to eradicate dysplastic and metaplastic tissues. Hybrid argon plasma coagulation (hybrid-APC) utilizes submucosal fluid injection to create a protective cushion prior to ablation that shields the submucosa from injury. We performed a pooled meta-analysis to evaluate the safety and efficacy of hybrid-APC. METHODS: We conducted a systematic search of major electronic databases in April 2022. Studies that included patients with dysplastic and non-dysplastic Barrett's esophagus undergoing treatment with hybrid-APC were eligible for inclusion. Outcome measures included complete remission of intestinal metaplasia (CR-IM), stricture formation, serious adverse events, and number of sessions necessary to achieve CR-IM. RESULTS: Overall pooled CR-IM rate for patients undergoing hybrid-APC was 90.8% (95% confidence interval [CI], 0.872-0.939; I2=0%). Pooled stricture rate was 2.0% (95% CI, 0.005-0.042; I2=0%). Overall serious adverse event rate was 2.7% (95% CI, 0.007-0.055; I2=0%). CONCLUSION: Results of the current meta-analysis suggest that hybrid-APC is associated with high rates of CR-IM and a favorable safety profile. Interpretation of these results is limited by the inclusion of retrospective cohort and case series data. Randomized controlled trials that standardize treatment and outcome evaluation protocols are necessary to understand how this treatment option is comparable to the current standards of care.

Bioremediation and tolerance of humans to heavy metals through microbial processes: a potential role for probiotics?

The food and water we consume are often contaminated with a range of chemicals and heavy metals, such as lead, cadmium, arsenic, chromium, and mercury, that are associated with numerous diseases. Although heavy-metal exposure and contamination are not a recent phenomenon, the concentration of metals and the exposure to populations remain major issues despite efforts at remediation. The ability to prevent and manage this problem is still a subject of much debate, with many technologies ineffective and others too expensive for practical large-scale use, especially for developing nations where major pollution occurs. This has led researchers to seek alternative solutions for decontaminating environmental sites and humans themselves. A number of environmental microorganisms have long been known for their ability to bind metals, but less well appreciated are human gastrointestinal bacteria. Species such as Lactobacillus, present in the human mouth, gut, and vagina and in fermented foods, have the ability to bind and detoxify some of these substances. This review examines the current understanding of detoxication mechanisms of lactobacilli and how, in the future, humans and animals might benefit from these organisms in remediating environmental contamination of food.

EUS and secretin endoscopic pancreatic function test predict evolution to overt structural changes of chronic pancreatitis in patients with nondiagnostic baseline imaging.

BACKGROUND AND OBJECTIVES: The accuracy of EUS and endoscopic pancreatic function test (ePFT) for diagnosis of early or minimal-change chronic pancreatitis (MCCP) is poorly understood. We hypothesized that the natural history of the disease may be used as a "gold standard" to assess the ability of EUS and ePFT to predict the eventual development of overt chronic pancreatitis (CP) changes on computed tomography/magnetic resonance cholangiopancreatography (CT/MRCP). The aim of the study was to determine the ability of EUS and ePFT to predict disease progression in patients with suspected MCCP who had nondiagnostic baseline imaging. METHODS: A retrospective cohort study was conducted. Patients who underwent EUS and ePFT for suspected CP and who had nondiagnostic CT or MRCP were included. Patients without repeat imaging performed more than 1 year after their initial EUS/ePFT were excluded. Imaging was considered diagnostic if calcifications, main duct dilation (Cambridge Class III/IV), or severe atrophy were identified. Patients lost to follow-up were contacted to complete a survey documenting current symptoms and whether patients progressed to CP based on imaging. Univariable and multivariable analyses were performed using Cox regression. RESULTS: Two hundred and thirty patients who underwent EUS/ePFT for suspected MCCP were identified between 2006 and 2012. Of these, 90 had a non-diagnostic baseline imaging test and subsequently a follow-up imaging test greater than 1 year later. These 90 patients constituted our study population. During a mean follow-up of 7 years, 19 (21%) patients developed CP by histology and imaging. Abnormal ePFT (peak bicarbonate <80 mmol) was a significant predictor of progression (hazard ratio [HR]: 4.7, confidence interval [CI]: 1.8, 12.4). Likewise, EUS Rosemont classification "suggestive/most-consistent" was a significant predictor of progression (HR: 7.3, CI: 2.4, 22.1). CONCLUSIONS: In patients with abdominal pain of suspected pancreatic origin and with nondiagnostic cross-sectional imaging, EUS and ePFT results predict the development of classic CP structural changes over time. These results support EUS and ePFT as effective tools for predicting progression of minimal change to overt CP.

Standard reporting elements for the performance of EUS: Recommendations from the FOCUS working group.

BACKGROUND AND OBJECTIVES: Quality indicators for the performance of EUS have been developed to monitor and improve service value and patient outcomes. To support the incorporation of these indicators and standardize EUS documentation, we propose standard EUS reporting elements for endosonographers and endoscopy units. METHODS: A comprehensive literature search and review was performed to identify EUS quality indicators and key components of high-quality standardized EUS reporting. Guidance statements regarding standard EUS reporting elements were developed and reviewed at the Forum for Canadian Endoscopic Ultrasound (FOCUS) 2019 Annual Meeting. RESULTS: EUS reporting elements can be divided into preprocedural, intraprocedural, and postprocedural items. Preprocedural components include the type, indication, and urgency of the procedure and patient clinical information and consent. Intraprocedural components include the adequacy and extent of examination, relevant landmarks, lesion characteristics, sampling method, specimen quality, and intraprocedural adverse events. Postprocedural components include a summary and synthesis of relevant findings as well as recommended management and follow-up. CONCLUSIONS: Standardizing reporting elements may help improve the care of patients undergoing EUS procedures. Our review provides a practical guide and compilation of recommended reporting elements to ensure ongoing best practices and quality improvement in EUS.

Immobilization of cadmium and lead by Lactobacillus rhamnosus GR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium.

Heavy metals are highly toxic elements that contaminate the global food supply and affect human and wildlife health. Purification technologies are often too expensive or not practically applicable for large-scale implementation, especially in impoverished nations where heavy metal contamination is widespread. Lactobacillus rhamnosus GR-1 (LGR-1) was shown in previous work to reduce heavy metal bioaccumulation in a Tanzanian cohort of women and children through indeterminant mechanisms. Here, it was hypothesized that LGR-1 could sequester the heavy metals lead (Pb) and cadmium (Cd), thereby reducing their absorption across intestinal epithelium. LGR-1 and other lactobacilli significantly reduced the amount of Pb and Cd in solution at all concentrations tested (0.5 mg/L - 50 mg/L) and exhibited sustained binding profiles over a 48-hour period. Relative binding efficiency of LGR-1 decreased as Pb concentration increased, with an absolute minimum binding threshold apparent at concentrations of 2 mg/L and above. Electron microscopy revealed that Pb formed irregular cell-surface clusters on LGR-1, while Cd appeared to form intracellular polymeric clusters. Additionally, LGR-1 was able to significantly reduce apical-to-basolateral translocation of Pb and Cd in a Caco-2 model of the intestinal epithelium. These findings demonstrate the absorbent properties of LGR-1 can immobilize Pb and Cd, effectively reducing their translocation across the intestinal epithelium in vitro. Oral administration of heavy metal-binding Lactobacillus spp. (many of which are known human symbionts and strains of established probiotics) may offer a simple and effective means to reduce the amount of heavy metals absorbed from foods in contaminated regions of the world.

Outcome of thyroid ultrasound screening in FAP patients with a normal baseline exam.

Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome associated with a substantial lifetime risk for colorectal cancer. The leading extra-colonic causes of cancer in FAP include duodenal and thyroid cancer (TC). Recent guidelines recommend annual thyroid ultrasound (TUS) screening beginning in the teenage years but the evidence to support the interval particularly in FAP patients with a normal baseline ultrasound is lacking. TUS results from FAP patients enrolled in a thyroid screening program from 2006 to 2016 and who had at least 2 TUS were reviewed. TUS findings were classified as normal, low (LR) or high risk (HR) for TC based on nodule characteristics as determined by American Thyroid Association (ATA) guidelines. We assessed the incidence of TC in patient with normal baseline TUS and factors associated with TC. 264 FAP patients were included. Baseline TUS was normal in 167, LR in 74, and HR in 24 patients. Patients were observed for a mean 4.8 years and underwent an average of 3 TUS. Patients with normal baseline TUS did not develop TC during the course of follow up of 5.1 years. TC developed in 6 patients (2.3%) all with baseline nodules; 5 in the LR group and 1 in the HR group. Factors associated with development of TC were presence of baseline nodule(s) and female sex. The development of TC in FAP patients in a TUS screening program with short term follow up is low and no FAP patient with a normal baseline TUS developed TC during observation. Annual TUS in patients with a normal baseline TUS may not be needed. Extending the screening interval to 2 years may be reasonable until nodules are detected.

The rationale for probiotics improving reproductive health and pregnancy outcome.

PROBLEM: Medical problems of most importance to reproductive health of women differ to some extent between the developed world and resource-disadvantaged countries. Nevertheless, many share a common link in microbial involvement. METHOD OF STUDY: A review of the peer-reviewed literature on microbiota, probiotics, and reproductive health. RESULTS: Indigenous and probiotic lactobacilli express properties antagonistic to pathogens, but complementary to host immunity. These organisms are associated with conception, reducing the risk of infection, as well as potentially lowering the risk of a number of complications of pregnancy that otherwise lead to maternal and infant mortality and morbidity. CONCLUSIONS: The ability to manipulate the microbiome and to improve immunity through probiotics holds much promise. The lack of improvements over the past 40 years in managing urogenital infections in women is incomprehensible. Support for innovative diagnostic and treatment options is needed, including testing and implementing probiotic therapies, especially for women with poor access to healthcare and good nutrition.

Probiotics and prebiotics to combat enteric infections and HIV in the developing world: a consensus report.

Infectious disease in the developing world continues to represent one of the greatest challenges facing humanity. Every year over a million children suffer and die from the sequela of enteric infections, while in 2008 it is estimated almost 2.7 million (UNAIDS 2009 update) adults and children became infected with human immunodeficiency virus (HIV). While oral rehydration therapy for diarrhea, and antiretrovirals (ARV) for HIV are critical, there is a place for adjunctive therapies to improve quality of life. The importance of the human microbiota in retaining health is now recognized, as is the concept of replenishing beneficial microbes through probiotic treatments. Studies have shown that probiotics can reduce the duration of diarrhea, improve gut barrier function, help prevent bacterial vaginosis (BV), and enhance immunity even in HIV-infected subjects. However, many issues remain before the extent of probiotic benefits can be verified, and their application to the developing world realised. This consensus report outlines the potential probiotic, and to a lesser extent prebiotic, applications in resource disadvantages settings, and recommends steps that could bring tangible relief to millions of people. The challenges to both efficacy and effectiveness studies in these settings include a lack of infrastructure and funding for scientists, students and research projects in developing countries; making available clinically proven probiotic and prebiotic products at affordable prices; and undertaking appropriately designed clinical trials. We present a roadmap on how efficacy studies may be conducted in a resource disadvantages setting among persons with chronic diarrhea and HIV. These examples and the translation of efficacy into effectiveness are described.