Impact of study design on adenoma detection in the evaluation of artificial intelligence-aided colonoscopy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Randomized controlled trials (RCTs) have reported that artificial intelligence (AI) improves endoscopic polyp detection. Different methodologies-namely, parallel and tandem designs-have been used to evaluate the efficacy of AI-assisted colonoscopy in RCTs. Systematic reviews and meta-analyses have reported a pooled effect that includes both study designs. However, it is unclear whether there are inconsistencies in the reported results of these 2 designs. Here, we aimed to determine whether study characteristics moderate between-trial differences in outcomes when evaluating the effectiveness of AI-assisted polyp detection. METHODS: A systematic search of Ovid MEDLINE, Embase, Cochrane Central, Web of Science, and IEEE Xplore was performed through March 1, 2023, for RCTs comparing AI-assisted colonoscopy with routine high-definition colonoscopy in polyp detection. The primary outcome of interest was the impact of study type on the adenoma detection rate (ADR). Secondary outcomes included the impact of the study type on adenomas per colonoscopy and withdrawal time, as well as the impact of geographic location, AI system, and endoscopist experience on ADR. Pooled event analysis was performed using a random-effects model. RESULTS: Twenty-four RCTs involving 17,413 colonoscopies (AI assisted: 8680; non-AI assisted: 8733) were included. AI-assisted colonoscopy improved overall ADR (risk ratio [RR], 1.24; 95% confidence interval [CI], 1.17-1.31; I2 = 53%; P < .001). Tandem studies collectively demonstrated improved ADR in AI-aided colonoscopies (RR, 1.18; 95% CI, 1.08-1.30; I2 = 0%; P < .001), as did parallel studies (RR, 1.26; 95% CI, 1.17-1.35; I2 = 62%; P < .001), with no statistical subgroup difference between study design. Both tandem and parallel study designs revealed improvement in adenomas per colonoscopy in AI-aided colonoscopies, but this improvement was more marked among tandem studies (P < .001). AI assistance significantly increased withdrawal times for parallel (P = .002), but not tandem, studies. ADR improvement was more marked among studies conducted in Asia compared to Europe and North America in a subgroup analysis (P = .007). Type of AI system used or endoscopist experience did not affect overall improvement in ADR. CONCLUSIONS: Either parallel or tandem study design can capture the improvement in ADR resulting from the use of AI-assisted polyp detection systems. Tandem studies powered to detect differences in endoscopic performance through paired comparison may be a resource-efficient method of evaluating new AI-assisted technologies.

Enhancing Self-Management of Percutaneous Endoscopic Gastrostomy Tubes Through the Implementation of a Standardized Education and Assessment Pathway: A Quality Improvement Initiative.

Intraduodenal infusion of levodopa-carbidopa intestinal gel by percutaneous endoscopic gastrostomy tube with jejunal extension is a treatment option to reduce motor and nonmotor complications in patients with advanced Parkinson's disease when oral therapy no longer provides sufficient benefit. Medication management is of central focus; however, there was no standardized patient education on stoma-site care and tube maintenance, leading to the development of stoma-site complications. As a quality improvement (QI) initiative, a standardized education and assessment pathway was developed and implemented in an urban academic outpatient clinic to enhance patient self-management and reduce stoma-site complications. A retrospective chart review was conducted to establish baseline incidence of cutaneous stoma-site complications. QI interventions were implemented using a rapid-cycle improvement model. Routine stoma assessments by a nurse who specializes in wound, ostomy, and continence care were implemented at set points, and patient education on PEG tube care and maintenance was reinforced at each session. Results demonstrated a significant reduction in moderate-to-severe tube and stoma-site-related complication. Implementation of a similar standardized education and assessment pathway in patients with percutaneous endoscopic gastrostomy tubes may lead to a decrease in stoma-site-related complications and overall better patient self-management.

Afatinib triggers a Ni2+ -resistant Ca2+ influx pathway in A549 non-small cell lung cancer cells.

Afatinib is used to treat non-small cell lung cancer cells (NSCLC), and its mechanism involves irreversible inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase. In this study, we examined if afatinib had cytotoxic action against NSCLC other than inhibition of tyrosine kinase. Afatinib (1-30 µM) caused apoptotic death in A549 NSCLC in a concentration-dependent manner. Afatinib triggered Ca2+ influx without causing Ca2+ release, and the Ca2+ influx was unaffected by sodium orthovanadate (SOV, an inhibitor of tyrosine phosphatase), suggesting that afatinib-triggered Ca2+ response was unrelated to its inhibition of tyrosine kinase. Addition of afatinib also promoted Mn2+ influx. Ca2+ influx triggered by afatinib was resistant to SKF96365 and ruthenium red (two general blockers of TRP channels) and, unexpectedly, Ni2+ (a non-specific Ca2+ channel blocker). Afatinib caused an increase in mitochondrial Ca2+ level, an initial mitochondrial hyperpolarization (4 h) and followed by mitochondrial potential collapse (24-48 h). Afatinib-induced cell death was slightly but significantly alleviated in low extracellular Ca2+ condition or under pharmacological block of mitochondrial permeability transition pore (MPTP) opening by cyclosporin A. Therefore, in addition to tyrosine kinase inhibition as a major anti-cancer mechanism of afatinib, stimulation of an atypical Ca2+ influx pathway, mitochondrial Ca2+ overload, and potential collapse in part contribute to afatinib-induced cell death.

MiniBooNE and MicroBooNE Combined Fit to a 3+1 Sterile Neutrino Scenario.

This Letter presents the results from the MiniBooNE experiment within a full "3+1" scenario where one sterile neutrino is introduced to the three-active-neutrino picture. In addition to electron-neutrino appearance at short baselines, this scenario also allows for disappearance of the muon-neutrino and electron-neutrino fluxes in the Booster Neutrino Beam, which is shared by the MicroBooNE experiment. We present the 3+1 fit to the MiniBooNE electron-(anti)neutrino and muon-(anti)neutrino data alone and in combination with MicroBooNE electron-neutrino data. The best-fit parameters of the combined fit with the exclusive charged-current quasielastic analysis (inclusive analysis) are Δm^{2}=0.209 eV^{2}(0.033 eV^{2}), |U_{e4}|^{2}=0.016(0.500), |U_{µ4}|^{2}=0.500(0.500), and sin^{2}(2θ_{µe})=0.0316(1.0). Comparing the no-oscillation scenario to the 3+1 model, the data prefer the 3+1 model with a Δχ^{2}/d.o.f.=24.7/3(17.3/3), a 4.3σ(3.4σ) preference assuming the asymptotic approximation given by Wilks's theorem.

Clinical implication of genetic composition and molecular mechanism on treatment strategies of HER2-positive breast cancers.

The current clinical management model of HER2-positive breast cancers is commonly based on guidelines, which in turn are based on the design and outcome of clinical trials. While this model is useful to most practicing clinicians, the treatment outcome of individual patient is not certain at the start of treatment. As the understanding of the translational research of carcinogenesis and the related changes in cancer genetics and tumor microenvironment during treatment is critical in the selection of right choice of treatment to maximize the successful clinical outcome for the patient, this review article intends to discuss the latest developments in the genetic and molecular mechanisms of cancer progression and treatment resistance, and how they influence the planning of the treatment strategies of HER2-positive breast cancers.

First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

Variable or Fixed? Exploring Entrustment Decision Making in Workplace- and Simulation-Based Assessments.

PURPOSE: Many models of competency-based medical education (CBME) emphasize assessing entrustable professional activities (EPAs). Despite the centrality of EPAs, researchers have not compared rater entrustment decisions for the same EPA across workplace- and simulation-based assessments. This study aimed to explore rater entrustment decision making across these 2 assessment settings. METHOD: An interview-based study using a constructivist grounded theory approach was conducted. Gastroenterology faculty at the University of Toronto and the University of Calgary completed EPA assessments of trainees' endoscopic polypectomy performance in both workplace and simulation settings between November 2019 and January 2021. After each assessment, raters were interviewed to explore how and why they made entrustment decisions within and across settings. Transcribed interview data were coded iteratively using constant comparison to generate themes. RESULTS: Analysis of 20 interviews with 10 raters found that participants (1) held multiple meanings of entrustment and expressed variability in how they justified their entrustment decisions and scoring, (2) held personal caveats for making entrustment decisions "comfortably" (i.e., authenticity, task-related variability, opportunity to assess trainee responses to adverse events, and the opportunity to observe multiple performances over time), (3) experienced cognitive tensions between formative and summative purposes when assessing EPAs, and (4) experienced relative freedom when using simulation to formatively assess EPAs but constraint when using only simulation-based assessments for entrustment decision making. CONCLUSIONS: Participants spoke about and defined entrustment variably, which appeared to produce variability in how they judged entrustment across participants and within and across assessment settings. These rater idiosyncrasies suggest that programs implementing CBME must consider how such variability affects the aggregation of EPA assessments, especially those collected in different settings. Program leaders might also consider how to fulfill raters' criteria for comfortably making entrustment decisions by ensuring clear definitions and purposes when designing and integrating workplace- and simulation-based assessments.

A basal level of γ-linolenic acid depletes Ca2+ stores and induces endoplasmic reticulum and oxidative stresses to cause death of breast cancer BT-474 cells.

Gamma-linolenic acid (GLA), a natural fatty acid obtained from oils of various vegetables and seeds, has been demonstrated as an anticancer agent. In this work, we investigated the anticancer effects of GLA on breast cancer BT-474 cells. GLA at 30 µM, a concentration reportedly within the range of circulating concentrations in clinical studies, caused apoptotic cell death. GLA caused an elevation in mitochondrial Ca2+ level and a decrease in mitochondrial membrane potential. GLA treatment depleted cyclopiazonic acid (CPA)-sensitive Ca2+ store and triggered substantial Ca2+ influx. Intracellular Ca2+ release triggered by GLA was suppressed by 3 µM xestospongin C (XeC, IP3 receptor-channel blocker) and 100 µM ryanodine (ryanodine receptor-channel blocker), suggesting that the Ca2+ release was via IP3 receptor-channel and ryanodine receptor-channel. Increased expressions of p-eIF2α and CHOP were observed in GLA-treated cells, suggesting GLA-treated cells had increased expressions of p-eIF2α and CHOP, which suggest endoplasmic reticulum (ER) stress. In addition, GLA elicited increased production of reactive oxygen species. Taken together, our results suggest a basal level of GLA induced apoptotic cell death by causing Ca2+ overload, mitochondrial dysfunction, Ca2+ store depletion, ER stress, and oxidative stress. This is the first report to show that GLA caused Ca2+ store depletion and ER stress. GLA-induced Ca2+ store depletion resulted from opening of IP3 receptor-channel and ryanodine receptor-channel.

Lipotoxicity in human lung alveolar type 2 A549 cells: Mechanisms and protection by tannic acid.

Palmitic acid (PA) is a saturated free fatty acid which, when being excessive, accounts for lipotoxicity. Using human lung A549 cells as a model for lung alveolar type 2 epithelial cells, we found that challenge of A549 cells with PA resulted in apoptotic cell death, as reflected by positive annexin V and PI staining, and also appearance of cleaved caspase-3. PA treatment also caused depletion of intracellular Ca2+ store, endoplasmic reticulum (ER) stress, and oxidative stress. Tannic acid (TA), a polyphenol present in wines and many beverages, alleviated PA-induced ER stress, oxidative stress and apoptotic death. Thus, our results suggest PA lipotoxicity in lung alveolar type 2 epithelial cells could be protected by TA.

Development and prospective validation of a scoring system for the Basic Endoscopic Skills Training (BEST) box.

AIMS: The increased use of endoscopy as a minimally invasive therapeutic technique has created a great demand for endoscopic training. The Basic Endoscopic Skills Training (BEST) box provides a low-cost solution by adapting the Fundamentals of Laparoscopic Surgery (FLS) box for flexible endoscopic simulation. The BEST box consists of six endoscopic tasks with a 5-min time limit per task. This study aims to develop a scoring system for objective evaluation of user performance. METHODS: A total of 165 participants were tested on the BEST box. Participants were divided into two groups: retrospective analysis (n = 100) and prospective analysis (n = 65). From the retrospective group, 55 individuals were also scored on the Global Assessment of Gastrointestinal Endoscopic Skills-Upper Endoscopy (GAGES-UE). Linear regression between user performance on BEST box and GAGES-UE was performed to develop the scoring system. Receiver Operating Characteristic curve was used to determine a threshold score to help users appreciate their endoscopic expertise. Prospective scoring of 65 individuals was then performed using the formula developed (20 experts and 45 trainees). RESULTS: The minimum and maximum possible scores are 30 and 110, respectively. Retrospective analysis showed that the scoring system was able to distinguish between experts and trainees (p < 0.001), correlated with GAGES-UE (p < 0.001), and had a reliability constant of r = 0.765 (p < 0.001). On prospective testing using the scoring system the expert group received a final average score of 92, whereas the average score for the trainee group was 61 (p < 0.001). CONCLUSIONS: The developed BEST box scoring system correlates with the experience level of the test taker as well as with the GAGES-UE scoring system. The results of this study add further evidence to the validity of the BEST box as an effective, low-cost endoscopic simulator with the scores used by trainees to track their performance level overtime.

Meeting the Motility Educational Requirements of the Gastroenterology Trainee in the 21st Century.

BACKGROUND: Gastrointestinal (GI) motility and functional disorders comprise over two-third of referrals to GI specialists yet training programs are disproportionately focused on endoscopy, inflammatory bowel disease and liver disease. Trainees at many centres receive minimal or no formal training in motility disorders and have little or no exposure to motility testing. Our purpose was to develop an educational intervention to address this learning need. METHODS: We designed a formal training program comprised of didactic sessions, workshops and hands-on motility sessions with live demonstrations designed to be held over the course of a weekend. Faculty for the course were experienced GI motility experts from across Canada. Resident trainees from all Canadian GI fellowship programs were invited to attend. Pre- and post-tests were administered to measure the baseline learning needs and the impact of the program. Course evaluations were completed by attendees. RESULTS: Three annual courses were offered over the past 3 years. Both adult and paediatric gastroenterology trainees attended the programs. The majority of training programs from Canada were represented. Baseline testing of attendees revealed a fundamental lack of understanding of GI motility concepts and their clinical implications. Postcourse test scores demonstrated a significant improvement in motility knowledge. Course evaluations of the content and faculty presentations received uniformly positive reviews. CONCLUSIONS: There is a pervasive lack of clinical knowledge of GI motility among Canadian GI subspecialty trainees. A focused weekend intensive course is one step in addressing this learning need.

Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study.

PURPOSE: This randomized, double-blind, placebo-controlled, parallel-group, phase II trial assessed the efficacy and safety of adagloxad simolenin (OBI-822; a Globo H epitope covalently linked to keyhole limpet hemocyanin (KLH)) with adjuvant OBI-821 in metastatic breast cancer (MBC). METHODS: At 40 sites in Taiwan, USA, Korea, India, and Hong Kong, patients with MBC of any molecular subtype and ≤2 prior progressive disease events with stable/responding disease after the last anticancer regimen were randomized (2:1) to adagloxad simolenin (AS/OBI-821) or placebo, subcutaneously for nine doses with low-dose cyclophosphamide. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, correlation of clinical outcome with humoral immune response and Globo H expression, and safety. RESULTS: Of 349 patients randomized, 348 received study drug. Patients with the following breast cancer subtypes were included: hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) (70.4%), triple negative (12.9%), and HER2+ (16.7%), similarly distributed between treatment arms. Median PFS was 7.6 months (95% CI: 6.5-10.9) with AS/OBI-821 (n=224) and 9.2 months (95% CI: 7.3-11.3) with placebo (n=124) (HR=0.96; 95% CI: 0.74-1.25; p=0.77), with no difference by breast cancer subtype. AS/OBI-821 recipients with anti-Globo H IgG titer ≥1:160 had significantly longer median PFS (11.1 months (95% CI: 9.3-17.6)) versus those with titers <1:160 (5.5 months (95% CI: 3.7-5.6); HR=0.52; p<0.0001) and placebo recipients (HR=0.71; p=0.03). Anti-KLH immune responses were similar at week 40 between AS/OBI-821 recipients with anti-Globo IgG titer ≥1:160 and those with anti-Globo IgG titer <1:160. The most common adverse events with AS/OBI-821 were grade 1 or 2 injection site reactions (56.7%; placebo, 8.9%) and fever (20.1%; placebo, 6.5%). CONCLUSION: AS/OBI-821 did not improve PFS in patients with previously treated MBC. However, humoral immune response to Globo H correlated with improved PFS in AS/OBI-821 recipients, leading the way to further marker-driven studies. Treatment was well tolerated.NCT01516307.

Advances in EGFR/HER2-directed clinical research on breast cancer.

The discovery of the HER2 molecules has embarked a series of investigations on the efficacy and safety of different types of anti-HER2 therapies for treating breast cancer, with the clinical pathway requiring a more detailed, more precise, and more dynamics therapeutic approaches due to the heterogeneity of the disease. As the "do more" and "do less" approaches are becoming more important to personalize treatment for early HER2-positive breast cancer, recent advances aim at tackling the advanced stage of the disease by using novel therapeutic agents and combination strategies. There are also important points of consideration on prognosis and choice of therapies, including HER2 gene copy number, HER2 heterogeneity, tissue biomarkers, blood-based biomarkers, and HER2 mutation and its treatment. Altogether, these could potentially play a vital role in the journey of HER2-positive breast cancer patient to achieve greater survival benefit and potentially a cure for the disease.

Optical Biopsy of the Upper GI Tract Using Fluorescence Lifetime and Spectra.

Screening and surveillance for gastrointestinal (GI) cancers by endoscope guided biopsy is invasive, time consuming, and has the potential for sampling error. Tissue endogenous fluorescence spectra contain biochemical and physiological information, which may enable real-time, objective diagnosis. We first briefly reviewed optical biopsy modalities for GI cancer diagnosis with a focus on fluorescence-based techniques. In an ex vivo pilot clinical study, we measured fluorescence spectra and lifetime on fresh biopsy specimens obtained during routine upper GI screening procedures. Our results demonstrated the feasibility of rapid acquisition of time-resolved fluorescence (TRF) spectra from fresh GI mucosal specimens. We also identified spectroscopic signatures that can differentiate between normal mucosal samples obtained from the esophagus, stomach, and duodenum.

Polyamine stimulation perturbs intracellular Ca2+ homeostasis and decreases viability of breast cancer BT474 cells.

Intracellular polyamines such as spermine and spermidine are essential to cell growth in normal and especially in cancer cells. However, whether extracellular polyamines affect cancer cell survival is unknown. We therefore examined the actions of extracellular polyamines on breast cancer BT474 cells. Our data showed that spermine, spermidine, and putrescine decreased cell viability by apoptosis. These polyamines also elicited Ca2+ signals, but the latter were unlikely triggered via Ca2+-sensing receptor (CaSR) as BT474 cells have been demonstrated previously to lack CaSR expression. Spermine-elicited Ca2+ response composed of both Ca2+ release and Ca2+ influx. Spermine caused a complete discharge of the cyclopiazonic acid (CPA)-sensitive Ca2+ pool and, expectedly, endoplasmic reticulum (ER) stress. The Ca2+ influx pore opened by spermine was Mn2+-impermeable, distinct from the CPA-triggered store-operated Ca2+ channel, which was Mn2+-permeable. Spermine cytotoxic effects were not due to oxidative stress, as spermine did not trigger reactive oxygen species formation. Our results therefore suggest that spermine acted on a putative polyamine receptor in BT474 cells, causing cytotoxicity by Ca2+ overload, Ca2+ store depletion, and ER stress.

The versatile Kv channels in the nervous system: actions beyond action potentials.

Voltage-gated K+ (Kv) channel opening repolarizes excitable cells by allowing K+ efflux. Over the last two decades, multiple Kv functions in the nervous system have been found to be unrelated to or beyond the immediate control of excitability, such as shaping action potential contours or regulation of inter-spike frequency. These functions include neuronal exocytosis and neurite formation, neuronal cell death, regulation of astrocyte Ca2+, glial cell and glioma proliferation. Some of these functions have been shown to be independent of K+ conduction, that is, they suggest the non-canonical functions of Kv channels. In this review, we focus on neuronal or glial plasmalemmal Kv channel functions which are unrelated to shaping action potentials or immediate control of excitability. Similar functions in other cell types will be discussed to some extent in appropriate contexts.

First Measurement of the Total Neutron Cross Section on Argon between 100 and 800 MeV.

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

Neratinib-based therapy in patients with metastatic HER2-positive breast cancer from Asia.

Aim: To evaluate the safety and efficacy of neratinib-based therapy in Asian patients with HER2-positive metastatic breast cancer (MBC). Patients & methods: We performed a pooled analysis of seven early-phase studies of neratinib given either as monotherapy or in combination with chemotherapeutic agents or trastuzumab in patients with advanced solid tumors. Results: A total of 793 patients with HER2-positive MBC were included in the efficacy analysis (Asia: 271 patients; other regions: 522 patients). The overall response rate in patients from Asia was 66.4% (180/271) and the median progression-free survival was 55.6 weeks. The most common adverse event in patients from Asia was diarrhea (all-grade: 96.3%; grade 3: 27.4%). Conclusion: Neratinib-based therapy is safe and effective in patients with HER2-positive MBC from Asia.

Efficacy of Biofeedback Therapy in Clinical Practice for the Management of Chronic Constipation and Fecal Incontinence.

BACKGROUND: Chronic constipation (CC) and fecal incontinence (FI) are often secondary to pelvic floor neuromuscular sensory or motor dysfunction. Biofeedback therapy (BFT) uses visual and verbal feedback to improve anorectal coordination, strength and sensation. In clinical trials, BFT demonstrated response rates between 70% and 80%. The purpose of this study is to determine the effectiveness of BFT in clinical practice. METHODS: In this retrospective observational cohort study, the charts of all patients who completed BFT at our centre were reviewed. A positive response to BFT was defined as improvement in ARM profile from baseline or subjective symptom improvement or both. Descriptive statistics were used to analyze the data. RESULTS: One hundred thirty patients with an average age of 57.5 ± 16.4 years and 79.2% female were included. Of all patients, 43.1% were referred for CC, 37.7% for FI, 16.9% for alternating CC and FI, and 2.3% for rectal pain. The overall response rate to BFT was 76.2% (n=99). Of those that responded, 64.6% (n=64) demonstrated both ARM and symptom improvement, 27.3% (n=27) had ARM improvement but no symptom improvement, and 8.1% (n=8) had symptom improvement but no ARM improvement. In patients with FI, the overall response rate was 79.6% (n=39) with symptom improvement in 67.3% (n=33). In those with CC with dyssynergic defecation (n=53), the overall response rate was 69.8% (n=37); however, only 45.3% (n=24) had symptomatic improvement. CONCLUSION: In our clinical practice, although overall response rates to BFT are similar to published reports, patients with CC with dyssynergic defecation are less likely to have symptomatic response compared with those with FI.