Neoplasia Diagnosis After Multi-target Stool DNA Is Enhanced Among Lowest Baseline Detectors.

BACKGROUND AND AIMS: Variation in colorectal neoplasia detection limits the effectiveness of screening colonoscopy. By evaluating neoplasia detection rates of individual colonoscopists, we aimed to quantify the effects of pre-procedural knowledge of a positive (+) multi-target stool DNA (mt-sDNA) on colonoscopy quality metrics. METHODS: We retrospectively identified physicians who performed a high volume of + mt-sDNA colonoscopies; colorectal neoplasia at post-mt-sDNA colonoscopy was recorded. These colonoscopists were stratified into quartiles based on baseline adenoma detection rates. Baseline colonoscopy adenoma detection rates and sessile serrated lesion detection rates were compared to post-mt-sDNA colonoscopy neoplasia diagnosis rates among each quartile. Withdrawal times were measured from negative exams. RESULTS: During the study period (2014-17) the highest quartile of physicians by volume of post-mt-sDNA colonoscopies were evaluated. Among thirty-five gastroenterologists, their median screening colonoscopy adenoma detection rate was 32% (IQR, 28-39%) and serrated lesion detection rate was 13% (8-15%). After + mt-sDNA, adenoma diagnosis increased to 47% (36-56%) and serrated lesion diagnosis increased to 31% (17-42%) (both p < 0.0001). Median withdrawal time increased from 10 (7-13) to 12 (10-17) minutes (p < 0.0001) and was proportionate across quartiles. After + mt-sDNA, lower baseline detectors had disproportionately higher rates of adenoma diagnosis in female versus male patients (p = 0.048) and higher serrated neoplasia diagnosis rates among all patients (p = 0.0092). CONCLUSIONS: Knowledge of + mt-sDNA enriches neoplasia diagnosis compared to average risk screening exams. Adenomatous and serrated lesion diagnosis was magnified among those with lower adenoma detection rates. Awareness of the mt-sDNA result may increase physician attention during colonoscopy. Pre-procedure knowledge of a positive mt-sDNA test improves neoplasia diagnosis rates among colonoscopists with lower baseline adenoma detection rates, independent of withdrawal time.

Results of Anorectal Physiological Testing in Patients with Limited English Proficiency.

BACKGROUND: Patients with limited English proficiency (LEP) experience barriers to healthcare. These include language barriers and difficulty accessing medical subspecialties. Consequently, patients with LEP may be underrepresented, and may be more likely to have abnormal results, among individuals referred for anorectal testing. AIMS: To explore whether differences exist in the results of high-resolution anorectal manometry (HRM), rectal sensory testing (RST), and balloon expulsion testing (BET) between patients with LEP and English proficiency (EP). METHODS: The electronic health records at Mayo Clinic, Rochester were used to identify constipated patients without organic anorectal disease who had undergone anorectal testing in 2018, 2019, and 2020. The language spoken by the patients was determined. HRM, RST, and BET results were compared. Nominal logistic regression explored the influence of age, gender, test operator, and LEP on the likelihood of abnormal findings. KEY RESULTS: Among 3298 patients (80% female, mean age ± standard deviation 46 ± 16 years), 67 (2%) had LEP. HRM measurements were similar in LEP and EP patients. However, LEP patients were more likely to have abnormal BET and RST. Logistic regression revealed that age (older than 50 years), gender, test operator, and LEP influenced the results of BET and RST, with LEP having the strongest influence. CONCLUSIONS: Results of anorectal testing in constipated patients differ between LEP and EP patients. This is likely to represent a difference in disease prevalence between these groups, for example, due to referral bias, rather than a difference in physiology or a language barrier.

Recto-anal Pressures in Constipated Men and Women Undergoing High-Resolution Anorectal Manometry.

BACKGROUND: In constipated individuals, high-resolution anorectal manometry (HRM) may suggest the presence of a defecatory disorder. Despite known physiological differences between men and women, our understanding of functional anorectal pathophysiology is based upon predominantly female cohorts. Results are generalized to men. AIMS: To evaluate whether recto-anal pressure patterns in constipated men are similar to those in constipated women. METHODS: The electronic health records at Mayo Clinic, Rochester were used to identify constipated adult patients, without organic anorectal disease, who had undergone HRM and balloon expulsion testing (BET) in 2018, 2019, and 2020. Comparative analyses were performed. RESULTS: Among 3,298 constipated adult patients (2,633 women, 665 men), anal and rectal pressures were higher in men. Women more likely to have HRM findings suggestive of a defecatory disorder (39% versus 20%, P < 0.001). Women were more likely to exhibit a type 4 pattern (27% versus 14%, P < 0.001), and less likely to exhibit a type 1 pattern (14% versus 38%, P < 0.001), of dyssynergia. Men were more likely to have an abnormal balloon expulsion test (BET, 34% versus 29%, P = 0.006). Nominal logistic regression demonstrates that male sex, age over 50 years, reduced recto-anal gradient during simulated evacuation, and types 2 and 4 dyssynergia are associated with an abnormal BET. CONCLUSIONS: In this large retrospective study, constipated men and women exhibited different patterns of dyssynergia both in the presence and absence of an abnormal BET. These findings were independent of sex-specific baseline physiological differences.

Retained Food During Esophagogastroduodenoscopy Is a Risk Factor for Gastric-to-Pulmonary Aspiration.

BACKGROUND: Residual food (RF) during esophagogastroduodenoscopy (EGD) is thought, but not proven, to be a risk factor for gastric-to-pulmonary aspiration. AIMS: The aims of this study were to determine the prevalence of RF during EGD, to investigate whether RF was associated with an increased risk of aspiration, especially when monitored anesthesia care (MAC) or general anesthesia (GA) were administered, and to determine whether aspiration associated with RF led to a more severe clinical outcome. METHODS: Patients undergoing EGD between October 2012 and September 2018 were identified. Patient age, sex, aspiration events, RF, sedation type, structural foregut abnormalities, and diagnoses associated with impaired esophageal or gastric motility were noted. The clinical course after an aspiration event was evaluated. RESULTS: RF was identified during 4% of 81,367 EGDs. Aspiration events occurred during 41 (5/10,000) procedures. Aspiration was more likely to occur in patients with RF (odds ratio [OR] 15.1) or those receiving MAC or GA (OR 9.6 and 16.8 relative to conscious sedation, respectively). RF and MAC/GA were synergistically associated with increased odds of aspiration. In a multivariate nominal logistic regression model, older age (OR 2.6), MAC (OR 3.8), GA (OR 4.4), vagotomy (OR 5.2), achalasia (OR 3.8), and RF (OR 10.0) were risk factors for aspiration. Aspiration events in the presence or absence of RF led to similar clinical outcomes. CONCLUSIONS: While aspiration events are rare in patients undergoing EGD, RF and the use of MAC or GA were associated with substantially increased odds of aspiration.

Retrospective evaluation of operator bias in the performance of high-resolution anorectal manometry.

BACKGROUND: Measurements obtained during high-resolution anorectal manometry (HRM) are subject to operator-patient interactions. For example, standardized enhanced instruction delivered by a single operator in a test-retest fashion did not consistently increase pressures generated during dynamic maneuvers. It is probable that factors other than verbal instruction effect communication during the procedure. To investigate this hypothesis, we retrospectively examined inter-operator variance in HRM results. METHODS: The electronic health records at Mayo Clinic, Rochester, were used to identify patients who had undergone HRM in 2019 and 2020. The analysis focused on constipated patients. The instructions given to the patients they had examined, and the pressure measurements obtained during HRM, by 6 different nurse operators were compared. KEY RESULTS: When performing HRM on their individual patients (range 126-673), the 6 nurses used similar instructions for each of the maneuvers and sensory testing thresholds. The proportion of patients with prolonged balloon expulsion tests and the rectal sensory thresholds were similar among operators. Significant variance was seen in the mean rectoanal pressures at rest, during squeeze, and during dynamic maneuvers. The proportion of patients with manometry results suggestive of a defecatory disorder differed between operators by 18% and 28% in women <50 and >50 years old, respectively. CONCLUSIONS & INFERENCES: Operators obtain significantly different results during HRM despite using similar instructions to patients. Substantial differences in the proportion of patients with manometry findings suggestive of a defecatory disorder among operators may have a significant impact on the diagnoses and therapies offered to constipated patients.

Urinary Symptoms and Bladder Voiding Dysfunction Are Common in Young Men with Defecatory Disorders: A Retrospective Evaluation.

BACKGROUND AND AIMS: Lower urinary tract symptoms (LUTS) are frequently reported by constipated patients. Prospective studies investigating the association between defecatory disorders (DDs) and voiding dysfunction, predominantly in women, have reported conflicting results. This study investigated (1) the prevalence of LUTS in young men with DDs and (2) the association between objectively documented DDs and voiding dysfunction in constipated young men with LUTS. METHODS: We reviewed the medical records, including validated questionnaires, of men aged 18-40 with confirmed DDs treated with pelvic floor physical therapy (PT) at our institution from May 2018 to November 2020. In a separate group of constipated young men with LUTS who underwent high-resolution anorectal manometry (HRM), rectal balloon expulsion test (BET), and uroflowmetry, we explored the relationship between DDs and voiding dysfunction. RESULTS: A total of 72 men were evaluated in the study. Among 43 men receiving PT for a proven DD, 82% reported ≥ 1 LUTS, most commonly frequent urination. Over half of these men experienced a reduction in LUTS severity after bowel-directed pelvic floor PT. Among 29 constipated men with LUTS who had undergone HRM/BET and uroflowmetry, 28% had concurrent defecatory and voiding dysfunction, 10% had DD alone, 14% had only voiding dysfunction, and 48% had neither. The presence of DD was associated with significantly increased odds of concurrent voiding dysfunction (odds ratio 9.3 [95% CI 1.7-52.7]). CONCLUSIONS: Most young men with DDs experience LUTS, which may respond to bowel-directed physical therapy. Patients with DD and urinary symptoms have increased odds of voiding dysfunction.

A prospective pilot study of the effects of deep brain stimulation on olfaction and constipation in Parkinson's disease.

BACKGROUND: Previous studies suggest deep brain stimulation of the subthalamic nucleus (STN-DBS) may improve olfaction and constipation in PD, using subjective measures. OBJECTIVE: To utilize objective measures to assess olfaction and constipation in PD following STN-DBS. METHODS: In this prospective pilot study, olfaction (University of Pennsylvania Smell Identification Test [UPSIT]), bowel symptoms (ROME III questionnaires, daily bowel diaries, 100 mm visual analog scales for satisfaction with treatment and bowel habits), and motor manifestations of PD were evaluated before and after STN-DBS. Levodopa equivalent daily dose (LEDD) was calculated. RESULTS: Ten patients (8 men, mean age 67.4 ± 6.0 years) with mean PD duration of 7.5 ± 3.7 years underwent bilateral STN-DBS, with mean follow-up of 3 months for all measures, except 7 months follow-up for bowel diaries. There was improvement in the Unified Parkinson's Disease Rating Scale motor "off" scores (33.7 ± 6.7 before and 16.1 ± 10.8 after, P = 0.001). Mean UPSIT scores (20.0 ± 6.6 versus 17.5 ± 5.7, P = 0.03) worsened from severe to total hyposmia. Seven patients had baseline constipation and completed bowel diaries. There was improvement in number of complete spontaneous bowel motions (CBSM) per week (2.2 ± 1.9 before versus 4.7 ± 2.4 after, P = 0.04), satisfaction with treatment of constipation (44 ± 27 before versus 64 ± 25 after, P = 0.02), and with bowel motions (33 ± 22 before and 48 ± 20 after, P = 0.2). However, laxative use (P = 0.15) and LEDD (P = 0.15) were unchanged. CONCLUSION: Olfaction worsened while symptoms of constipation improved but did not resolve after STN-DBS.

Detection of Postcolonoscopy Colorectal Neoplasia by Multi-target Stool DNA.

INTRODUCTION: Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose. METHODS: In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0-9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy. RESULTS: Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy. DISCUSSION: The high PPV of mt-sDNA 0-9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo. mt-sDNA as an interval test after negative screening colonoscopy warrants further study.

Relationship between symptoms during a gastric emptying study, daily symptoms and quality of life in patients with diabetes mellitus.

AIMS: Gastric emptying is of limited utility for predicting the severity of symptoms in patients with diabetes mellitus and gastrointestinal symptoms. We evaluated the extent to which symptoms recorded during a 13 C-spirulina-based gastric emptying breath test (GEBT) or scintigraphy predicting the severity of daily symptoms in diabetes mellitus. METHODS: Gastric emptying, symptoms during a gastric emptying study, either scintigraphy (n = 38) or GEBT (n = 111), and daily gastrointestinal symptoms were evaluated in 149 patients with diabetes mellitus and variably severe gastrointestinal symptoms. KEY RESULTS: Gastric emptying was normal, delayed, and rapid in 37%, 52%, and 9% measured with the GEBT and 55%, 34%, and 11% of patients measured with scintigraphy; differences between GEBT and scintigraphy were not significant. Daily symptoms were moderately severe or more intense in 58% and 21% of patients undergoing scintigraphy and GEBT (P < 0.0001). Symptoms during the GEBT (46%) and emptying thalf (3%) explained 50% of the variance in daily symptoms in the GEBT group. In the scintigraphy group, symptoms explained 29% of this variance; the thalf was insignificant. Patients who reported that one or more symptoms were more severe than the others during the GE study were more likely (OR 3.98, 95% CI 2.16, 7.33) to report the same symptom(s) as being the most severe in the daily diary. CONCLUSIONS: Symptoms during a GEBT and to a lesser extent during scintigraphy, but not gastric emptying predict the severity of daily symptoms and may serve as a biomarker in patients with diabetes mellitus.

Food Residue During Esophagogastroduodenoscopy Is Commonly Encountered and Is Not Pathognomonic of Delayed Gastric Emptying.

BACKGROUND AND AIMS: Retained gastric food (RGF) identified during esophagogastroduodenoscopy (EGD) is often attributed to gastroparesis. This retrospective study evaluated the prevalence of RGF, risk factors for RGF, and the association between RGF and delayed gastric emptying (GE). METHODS: The prevalence and odds ratios for RGF in patients with structural foregut abnormalities or medical risk factors for delayed GE were determined from 85,116 EGDs performed between 2012 and 2018. The associations between RGF, delayed GE, and medical comorbidities were evaluated in 2991 patients without structural abnormalities who had undergone EGD and gastric emptying scintigraphy. The relationship between medication use and RGF was evaluated in 249 patients without structural or medical risk factors for RGF. RESULTS: RGF was identified during 3% of EGDs. The odds of RGF were increased in patients with type 1 diabetes (12%, OR 1.7, P ≤ 0.001), type 2 diabetes (6%, OR 1.4, P ≤ 0.001), gastroparesis (14%, OR 4.8, P ≤ 0.001), amyloidosis (5%, OR 1.7, P ≤ 0.001), and structural foregut abnormalities (6%, OR 2.6, P ≤ 0.001). Overall, the PPV of RGF for delayed GE was 55%. However, the PPV varied from 32% in patients without risk factors to 79% in patients with type 1 diabetes. Opioids, cardiovascular medications, and acid suppressants were associated with RGF. CONCLUSIONS: RGF is common during EGD. The PPV of RGF for delayed GE varies depending on underlying risk factors (type 1 diabetes, type 2 diabetes, gastroparesis, and amyloidosis). Acid suppressants or antacids, cardiovascular medications, and opioids are associated with RGF independent of delayed GE.

Capsule Endoscopy Complements Magnetic Resonance Enterography and Endoscopy in Evaluating Small Bowel Crohn's Disease.

AIMS: Wireless capsule endoscopy (WCE) and magnetic resonance enterography (MRE) are increasingly utilized to evaluate the small bowel (SB) in Crohn's disease (CD). The primary aims were to compare the ability of WCE and MRE to detect SB inflammation in children with newly diagnosed CD, and in the terminal ileum (TI) to compare them to ileo-colonoscopy. Secondary aims were to compare diagnostic accuracy of WCE and MRE and changes in Paris classification after each study. METHODS: Patients (10 to 17 years of age) requiring ileo-colonoscopy for suspected CD were invited to participate. Only patients with endoscopic/histologic evidence of CD underwent MRE and WCE. SB inflammation and extent were documented and comparative analyses performed. RESULTS: Of 38 initially recruited subjects, 20 completed the study. WCE and MRE were similarly sensitive in identifying active TI inflammation (16 [80%] versus 12 [60%]) and any SB inflammation (17 [85%] versus 16 [80%]). However, WCE detected more extensive SB disease than MRE with active inflammation throughout the SB in 15 [75%] versus 1 [5%] patient (P < 0.001). Moreover, WCE was more likely to detect proximal SB disease (jejunum and ileum) compared to MRE (85% versus 50%, P = 0.04). Overall, the Paris classification changed in 65% and 85% of patients following MRE and WCE, respectively. CONCLUSIONS: WCE is as sensitive as MRE for identifying active TI inflammation, but appears more sensitive in identifying more proximal SB inflammation. In the absence of concern regarding stricturing or extra-luminal disease WCE can be considered for the evaluation of suspected SB CD.

Constipation and Fecal Incontinence in the Elderly.

PURPOSE OF REVIEW: To review the epidemiology, pathogenesis, clinical features, and management of primary constipation and fecal incontinence in the elderly. RECENT FINDINGS: Among elderly people, 6.5%, 1.7%, and 1.1% have functional constipation, constipation-predominant IBS, and opioid-induced constipation. In elderly people, the number of colonic enteric neurons and smooth muscle functions is preserved; decreased cholinergic function with unopposed nitrergic relaxation may explain colonic motor dysfunction. Less physical activity or dietary fiber intake and postmenopausal hormonal therapy are risk factors for fecal incontinence in elderly people. Two thirds of patients with fecal incontinence respond to biofeedback therapy. Used in combination, loperamide and biofeedback therapy are more effective than placebo, education, and biofeedback therapy. Vaginal or anal insert devices are another option. In the elderly, constipation and fecal incontinence are common and often distressing symptoms that can often be managed by addressing bowel disturbances. Selected diagnostic tests, prescription medications, and, infrequently, surgical options should be considered when necessary.

Multitarget Stool DNA Screening in Clinical Practice: High Positive Predictive Value for Colorectal Neoplasia Regardless of Exposure to Previous Colonoscopy.

OBJECTIVES: Multitarget stool DNA (MT-sDNA) testing has grown as a noninvasive screening modality for colorectal cancer (CRC), but real-world clinical data are limited in the post-FDA approval setting. The effect of previous colonoscopy on MT-sDNA performance is not known. We aimed to evaluate findings of colorectal neoplasia (CRN) at diagnostic colonoscopy in patients with positive MT-sDNA testing, stratified by patient exposure to previous colonoscopy. METHODS: We identified consecutive patients completing MT-sDNA testing over a 39-month period and reviewed the records of those with positive tests for neoplastic findings at diagnostic colonoscopy. MT-sDNA test positivity rate, adherence to diagnostic colonoscopy, and the positive predictive value (PPV) of MT-sDNA for any CRN and neoplastic subtypes were calculated. RESULTS: Of 16,469 MT-sDNA tests completed, testing returned positive in 2,326 (14.1%) patients. After exclusion of patients at increased risk for CRC, 1,801 patients remained, 1,558 (87%) of whom underwent diagnostic colonoscopy; 918 of 1,558 (59%) of these patients had undergone previous colonoscopy, whereas 640 (41%) had not. Any CRN was found in 1,046 of 1,558 patients (PPV = 67%). More neoplastic lesions were found in patients without previous colonoscopy (73%); however, the rates remained high among those who had undergone previous colonoscopy (63%, P < 0.0001). The large majority (79%) of patients had right-sided neoplasia. DISCUSSION: MT-sDNA has a high PPV for any CRN regardless of exposure to previous colonoscopy. Right-sided CRN was found at colonoscopy in most patients with positive MT-sDNA testing, representing a potential advantage over other currently available screening modalities for CRC.

Diabetic Gastroparesis.

This review covers the epidemiology, pathophysiology, clinical features, diagnosis, and management of diabetic gastroparesis, and more broadly diabetic gastroenteropathy, which encompasses all the gastrointestinal manifestations of diabetes mellitus. Up to 50% of patients with type 1 and type 2 DM and suboptimal glycemic control have delayed gastric emptying (GE), which can be documented with scintigraphy, 13C breath tests, or a wireless motility capsule; the remainder have normal or rapid GE. Many patients with delayed GE are asymptomatic; others have dyspepsia (i.e., mild to moderate indigestion, with or without a mild delay in GE) or gastroparesis, which is a syndrome characterized by moderate to severe upper gastrointestinal symptoms and delayed GE that suggest, but are not accompanied by, gastric outlet obstruction. Gastroparesis can markedly impair quality of life, and up to 50% of patients have significant anxiety and/or depression. Often the distinction between dyspepsia and gastroparesis is based on clinical judgement rather than established criteria. Hyperglycemia, autonomic neuropathy, and enteric neuromuscular inflammation and injury are implicated in the pathogenesis of delayed GE. Alternatively, there are limited data to suggest that delayed GE may affect glycemic control. The management of diabetic gastroparesis is guided by the severity of symptoms, the magnitude of delayed GE, and the nutritional status. Initial options include dietary modifications, supplemental oral nutrition, and antiemetic and prokinetic medications. Patients with more severe symptoms may require a venting gastrostomy or jejunostomy and/or gastric electrical stimulation. Promising newer therapeutic approaches include ghrelin receptor agonists and selective 5-hydroxytryptamine receptor agonists.

Recent advances in understanding and managing chronic constipation.

Constipation, a condition characterized by heterogeneous symptoms, is common in Western society. It is associated with reduced physical health, mental health, and social functioning. Because constipation is rarely due to a life-threatening disease (for example, colon cancer), current guidelines recommend empiric therapy. Limited surveys suggest that fewer than half of treated individuals are satisfied with treatment, perhaps because the efficacy of drugs is limited, they are associated with undesirable side effects, or they may not target the underlying pathophysiology. For example, although a substantial proportion of constipated patients have a defecatory disorder that is more appropriately treated with pelvic floor biofeedback therapy than with laxatives, virtually no pharmacological trials formally assessed for anorectal dysfunction. Recent advances in investigational tools have improved our understanding of the physiology and pathophysiology of colonic and defecatory functions. In particular, colonic and anorectal high-resolution manometry are now available. High-resolution anorectal manometry, which is increasingly used in clinical practice, at least in the United States, provides a refined assessment of anorectal pressures and may uncover structural abnormalities. Advances in our understanding of colonic molecular physiology have led to the development of new therapeutic agents (such as secretagogues, pro-kinetics, inhibitors of bile acid transporters and ion exchangers). However, because clinical trials compare these newer agents with placebo, their efficacy relative to traditional laxatives is unknown. This article reviews these physiologic, diagnostic, and therapeutic advances and focuses particularly on newer therapeutic agents.

Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin-αv trafficking.

The fundamental mechanisms underlying erosive oesophagitis and subsequent development of Barrett's oesophagus (BO) are poorly understood. Here, we investigated the contribution of specific components of the gastric refluxate on adhesion molecules involved in epithelial barrier maintenance. Cell line models of squamous epithelium (HET-1A) and BO (QH) were used to examine the effects of bile acids on cell adhesion to extracellular matrix proteins (Collagen, laminin, vitronectin, fibronectin) and expression of integrin ligands (α3 , α4, α5 , α6 and αν ). Experimental findings were validated in human explant oesophageal biopsies, a rat model of gastroesophageal reflux disease (GORD) and in patient tissue microarrays. The bile acid deoxycholic acid (DCA) specifically reduced adhesion of HET-1A cells to vitronectin and reduced cell-surface expression of integrin-αν via effects on endocytic recycling processes. Increased expression of integrin-αv was observed in ulcerated tissue in a rat model of GORD and in oesophagitis and Barrett's intestinal metaplasia patient tissue compared to normal squamous epithelium. Increased expression of integrin-αν was observed in QH BO cells compared to HET-1A cells. QH cells were resistant to DCA-mediated loss of adhesion and reduction in cell-surface expression of integrin-αν . We demonstrated that a specific component of the gastric refluxate, DCA, affects the epithelial barrier through modulation of integrin αν expression, providing a novel mechanism for bile acid-mediated erosion of oesophageal squamous epithelium and promotion of BO. Strategies aimed at preventing bile acid-mediated erosion should be considered in the clinical management of patients with GORD.

High-resolution Anorectal Manometry for Identifying Defecatory Disorders and Rectal Structural Abnormalities in Women.

BACKGROUND & AIMS: Contrary to conventional wisdom, the rectoanal gradient during evacuation is negative in many healthy people, undermining the utility of anorectal high-resolution manometry (HRM) for diagnosing defecatory disorders. We aimed to compare HRM and magnetic resonance imaging (MRI) for assessing rectal evacuation and structural abnormalities. METHODS: We performed a retrospective analysis of 118 patients (all female; 51 with constipation, 48 with fecal incontinence, and 19 with rectal prolapse; age, 53 ± 1 years) assessed by HRM, the rectal balloon expulsion test (BET), and MRI at Mayo Clinic, Rochester, Minnesota, from February 2011 through March 2013. Thirty healthy asymptomatic women (age, 37 ± 2 years) served as controls. We used principal components analysis of HRM variables to identify rectoanal pressure patterns associated with rectal prolapse and phenotypes of patients with prolapse. RESULTS: Compared with patients with normal findings from the rectal BET, patients with an abnormal BET had lower median rectal pressure (36 vs 22 mm Hg, P = .002), a more negative median rectoanal gradient (-6 vs -29 mm Hg, P = .006) during evacuation, and a lower proportion of evacuation on the basis of MRI analysis (median of 40% vs 80%, P < .0001). A score derived from rectal pressure and anorectal descent during evacuation and a patulous anal canal was associated (P = .005) with large rectoceles (3 cm or larger). A principal component (PC) logistic model discriminated between patients with and without prolapse with 96% accuracy. Among patients with prolapse, there were 2 phenotypes, which were characterized by high (PC1) or low (PC2) anal pressures at rest and squeeze along with higher rectal and anal pressures (PC1) or a higher rectoanal gradient during evacuation (PC2). CONCLUSIONS: In a retrospective analysis of patients assessed by HRM, measurements of rectal evacuation by anorectal HRM, BET, and MRI were correlated. HRM alone and together with anorectal descent during evacuation may identify rectal prolapse and large rectoceles, respectively, and also identify unique phenotypes of rectal prolapse.