Updates to the modern diagnosis of GERD: Lyon consensus 2.0.

The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.

The Diagnostic Performance of Fecal Immunochemical Tests for Detecting Advanced Neoplasia at Surveillance Colonoscopy.

BACKGROUND & AIMS: An increasing burden on health care resources has resulted in a backlog of individuals requiring colonoscopy, with delays in surveillance possibly detrimental for individuals at increased risk of colorectal cancer (CRC). This study investigated the use of a 2-sample fecal immunochemical test (FIT) to establish those most likely to have advanced neoplasia (AN) and in need of prioritized surveillance colonoscopy. METHODS: This was a prospective study conducted in the tertiary care setting. Participants completed a 2-sample FIT (OC-Sensor, Eiken Chemical Company) within 90 days of surveillance colonoscopy. The sensitivity of FIT for detection of AN (CRC or advanced adenoma) in moderate- and high-risk individuals was determined at fecal hemoglobin thresholds between 2 and 80 µg/g feces. RESULTS: A total of 766 patients were included (median age, 66.1 years [interquartile range, 58.1-72.9]; 49.9% male), with AN detected in 8.6% (66/766, including 5 CRC). For moderate-risk individuals (with prior history of adenoma or a significant family history of CRC), sensitivity of FIT for AN ranged from 73.5% at 2 µg/g feces, to 10.2% at 80 µg/g feces. For high-risk conditions (confirmed/suspected genetic syndromes or prior CRC), sensitivity of FIT was similar, ranging from 70.6% at the lowest positivity threshold of 2 µg/g feces, to 11.8% at 80 µg/g feces. Independent variables in the whole cohort for association with detection of AN at surveillance colonoscopy were age (odds ratio, 1.03; 95% confidence interval, 1.00-1.06) and FIT hemoglobin result ≥10 µg/g feces (odds ratio, 1.81; 95% confidence interval, 1.04-3.16). CONCLUSIONS: The use of FIT before surveillance colonoscopy provides clinicians with insights into the risk of AN. This raises the possibility of a method to triage individuals, facilitating the more efficient management of endoscopic resources.

Health utility assessments in individuals undergoing diagnostic and surveillance colonoscopy: improved discrimination with a cancer-specific scale.

PURPOSE: To compare the sensitivity and discriminant validity of generic and cancer-specific measures for assessing health-related quality of life (HRQoL) for individuals undergoing diagnostic or surveillance colonoscopy for colorectal cancer. METHODS: HRQoL was assessed using EQ-5D-5L (generic), and EORTC QLQ-C30 (cancer-specific) scales, 14 days after (baseline) and one-year following colonoscopy (follow-up). Utility scores were calculated by mapping EORTC-QLQ-C30 onto QLU-C10D. Differences between participants with different indications for colonoscopy (positive faecal occult blood test (FOBT), surveillance, or symptoms) and colonoscopy findings (no polyps, polyps, or cancer) were tested using Wilcoxon-Mann-Whitney and Kruskal-Wallis H tests. Sensitivity was assessed by calculating the ceiling effects (proportion reporting the best possible level). RESULTS: 246 adults completed the survey, including those undergoing colonoscopy for symptoms (n = 87), positive FOBT (n = 92) or surveillance (n = 67). Those with symptoms had the lowest HRQoL at both baseline and follow-up, with differences observed within the HRQoL domains/areas of role function, appetite loss and bowel function on the QLU-C10D. No differences were found in HRQoL when stratified by findings at colonoscopy with both measures or when comparing baseline and follow-up responses. Participants reporting full health with EQ-5D-5L (21% at baseline and 16% at follow-up) still had problems on the QLU-C10D, with fatigue and sleep at baseline and with role function and fatigue at follow-up. CONCLUSION: Patients undergoing colonoscopy for symptoms had lower HRQoL compared to surveillance or positive FOBT. The cancer-specific QLU-C10D was more sensitive and had greater discriminant ability between patients undergoing colonoscopy for different indications.

Assessment of laparoscopic fundoplication with endoscopy: room for improvement.

INTRODUCTION: Gastroesophageal reflux disease affects a significant portion of the Australian and world population. Minimally invasive laparoscopic fundoplication is a highly effective treatment in appropriately selected patients, with a 90% satisfaction rate. However, up to 5% will undergo revisional surgery. Endoscopy is an important investigation in the evaluation of persistent or new symptoms after fundoplication. Our study sought to evaluate the inter-rater reliability and variability in assessing fundoplication with endoscopy. METHODS: Upper gastrointestinal (UGI) surgeons and gastroenterologists were invited to join the cohort study through their professional membership with two societies based in Australia. Participants completed a two part 25-item multiple choice questionnaire, involving the analysis of ten static endoscopic images post-fundoplication. RESULTS: A total of 101 participants were included in the study (64 UGI surgeons and 37 gastroenterologists). Over 95% of participants were consultant level, working in non-rural tertiary hospitals. Total accuracy for all 10 cases combined was 76% for UGI surgeons and 69.9% for gastroenterologists. In three of the 10 cases, UGI surgeons performed significantly better than gastroenterologists (p < 0.05). When assessing performance across each of the 4 questions for each case, UGI surgeons were more accurate than gastroenterologists in describing the integrity of the wrap (p = 0.014). Inter-rater reliability was low across both groups for most domains (kappa < 1). CONCLUSION: Our study confirms low inter-rater reliability between endoscopists and large variations in reporting. UGI surgeons performed better than gastroenterologists in certain cases, usually when describing the integrity of the fundoplication. Our study provides further support for the use of a standardized reporting system in post-fundoplication patients.

Accuracy, Acceptability, and Application: Fecal Immunochemical Tests for Early Detection of Advanced Neoplasia in Colonoscopy-Based Surveillance.

BACKGROUND: The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening, but limited data exist for its application in individuals at above-average risk for CRC who complete surveillance colonoscopies. AIM: To assess the accuracy, acceptability, and effectiveness of FIT in the interval between surveillance colonoscopies, for predicting advanced neoplasia (advanced adenoma or CRC) at the next colonoscopy. METHODS: Individuals enrolled in an Australian surveillance program were included. Diagnostic accuracy was determined for 614 individuals completing a two-sample FIT (OC-Sensor) ≤ 3 months preceding surveillance colonoscopy. 386 Individuals were surveyed to assess acceptability of interval FIT. Additionally, a retrospective analysis was performed on 7331 individuals offered interval FIT between colonoscopies, where a positive FIT (≥ 20 µg hemoglobin/g feces) triggered an early colonoscopy. Associations between interval FIT results and advanced neoplasia were determined using regression analysis. RESULTS: FIT detected CRC and advanced adenoma with sensitivities of 60.0% (3/5) and 27.1% (35/129), respectively. Most (89.1%, 344/386) survey respondents preferred completing interval FIT every 1-2 years. The detection rate of interval FIT for advanced neoplasia decreased with increasing FIT completion. Individuals returning a positive FIT had a higher risk of advanced neoplasia than those who did not complete FIT. Positive interval FIT reduced time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively. CONCLUSION: Interval FIT was well accepted and enabled earlier detection of advanced neoplasia in individuals at above-average risk of CRC. Given that interval FIT predicts advanced neoplasia, it may be used to personalize surveillance colonoscopy intervals.

Multiple Negative Fecal Immunochemical Tests Reduce Risk of Advanced Neoplasia in a Colonoscopy Surveillance Program.

BACKGROUND & AIMS: In above-average-risk individuals undergoing colonoscopy-based surveillance for colorectal cancer (CRC), screening with fecal immunochemical tests (FIT) between colonoscopies might facilitate personalization of surveillance intervals. Because a negative FIT is associated with a reduced risk for CRC, we examined the relationship between number of rounds of negative FIT and risk for advanced neoplasia in individuals undergoing surveillance colonoscopy. METHODS: We conducted a retrospective cohort study on 4021 surveillance intervals in 3369 individuals (50-74 years), who had completed a 2-sample FIT between colonoscopies, from 1 to 4 rounds at 1-2 yearly intervals, each with a negative result (<20 µg hemoglobin/g feces). Incidence of advanced neoplasia (CRC or advanced adenoma) was determined at the follow-up colonoscopy. Competing-risk regression was used to assess the association between multiple negative FIT results and the risk of advanced neoplasia within 2 years. RESULTS: The incidence of advanced neoplasia in the cohort was 9.9% and decreased with increasing numbers of rounds of negative FIT results: 11.1% after 1 negative FIT to 5.7% after 4 negative FIT. The risk of advanced neoplasia was significantly lower in participants with 3 (subdistribution hazard ratio, 0.50; 95% confidence interval, 0.24-0.97) and 4 (subdistribution hazard ratio, 0.33; 95% confidence interval, 0.15-0.73) rounds of negative FIT compared with only 1 negative FIT. CONCLUSIONS: There was a low risk of advanced neoplasia after multiple rounds of negative FIT in above-average-risk people undergoing surveillance with no neoplasia or nonadvanced adenoma at prior colonoscopy. This supports the use of interval FIT to personalize surveillance by lengthening colonoscopy intervals following multiple negative FIT results.

Hot Mail: Temperature Exposure during Mail Return of an Immunochemical Fecal Occult Blood Test.

BACKGROUND: Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening; however, high ambient temperatures were found to reduce test accuracy. More recently, proprietary globin stabilizers were added to FIT sample buffers to prevent temperature-associated hemoglobin (Hb) degradation, but their effectiveness remains uncertain. We aimed to determine the impact of high temperature (>30°C) on OC-Sensor FIT Hb concentration with current FITs, characterize FIT temperatures during mail transit, and determine impact of ambient temperature on FIT Hb concentration using data from a CRC screening program. METHODS: FITs were analyzed for Hb concentration after in vitro incubation at different temperatures. Data loggers packaged alongside FITs measured temperatures during mail transit. Separately, screening program participants completed and mailed FITs to the laboratory for Hb analysis. Regression analyses compared the impact of environmental variables on FIT temperatures and separately on FIT sample Hb concentration. RESULTS: In vitro incubation at 30 to 35°C reduced FIT Hb concentration after >4 days. During mail transit, maximum FIT temperature averaged 6.4°C above maximum ambient temperature, but exposure to temperature above 30°C was for less than 24 hours. Screening program data showed no association between FIT Hb concentration and maximum ambient temperatures. CONCLUSIONS: Although FIT samples are exposed to elevated temperatures during mail transit, this is brief and does not significantly reduce FIT Hb concentration. These data support continuation of CRC screening during warm weather with modern FITs with a stabilizing agent when mail delivery is ≤4 days.

FIT for purpose: study protocol for a randomized controlled trial to personalize surveillance colonoscopy for individuals at elevated risk of colorectal cancer.

PURPOSE: There is increasing demand for colorectal cancer (CRC) surveillance, but healthcare capacity is limited. The burden on colonoscopy resources could be reduced by personalizing surveillance frequency using the fecal immunochemical test (FIT). This study will determine the safety, cost-effectiveness, and patient acceptance of using FIT to extend surveillance colonoscopy intervals for individuals at elevated risk of CRC. METHODS: This multicenter, prospective, randomized controlled trial will invite participants who are scheduled for surveillance colonoscopy (due to a personal history of adenomas or a family history of CRC) and who have returned a low fecal hemoglobin (< 2 µg Hb/g feces; F-Hb) using a two-sample FIT (OC Sensor, Eiken Chemical Company) in the prior 3 years. A total of 1344 individuals will be randomized to either surveillance colonoscopy as scheduled or delayed by 1 or 2 years for individuals originally recommended a 3- or 5-year surveillance interval, respectively. The primary endpoint is incidence of advanced neoplasia (advanced adenoma and/or CRC). Secondary endpoints include cost-effectiveness and consumer acceptability of extending surveillance intervals, determined using surveys and discrete choice experiments. CONCLUSION: This study will establish the safety, cost-effectiveness, and acceptability of utilizing a low FIT Hb result to extend colonoscopy surveillance intervals in a cohort at elevated risk for CRC. This personalized approach to CRC surveillance will lead to a reduction in unnecessary colonoscopies, increases in healthcare savings, and a better patient experience.  TRIAL REGISTRATION: Registration was approved on December 9, 2019 with the Australian New Zealand Clinical Trials Registry ANZCTR 12619001743156.

Low Incidence of Colorectal Advanced Neoplasia During Surveillance in Individuals with a Family History of Colorectal Cancer.

BACKGROUND: Family history of colorectal cancer (CRC) is used to stratify individuals into risk categories which determine timing of initial screening and ongoing CRC surveillance. Evidence for long-term CRC risk following a normal index colonoscopy in family history populations is limited. AIMS: To assess the incidence of advanced neoplasia and associated risk factors in a population undergoing surveillance colonoscopies due to family history of CRC. METHODS: Surveillance colonoscopy findings were examined in 425 individuals with a family history of CRC, a normal index colonoscopy and a minimum of 10 years of follow-up colonoscopies. Advanced neoplasia risk was determined for three CRC family history categories (near-average, medium and high-risk), accounting for demographics and time after the first colonoscopy. RESULTS: The median follow-up was 13.5 years (IQR 11.5-16.0), with an incidence of advanced neoplasia of 14.35% (61/425). The number of affected relatives and age of CRC diagnosis in the youngest relative did not predict the risk of advanced neoplasia (p > 0.05), with no significant differences in advanced neoplasia incidence between the family history categories (p = 0.16). Patients ≥ 60 years showed a fourfold (HR 4.14, 95% CI 1.33-12.89) higher advanced neoplasia risk during surveillance than those < 40 years at index colonoscopy. With each subsequent negative colonoscopy, the risk of advanced neoplasia at ongoing surveillance was reduced. CONCLUSIONS: The incidence of advanced neoplasia was low (14.35%), regardless of the family history risk category, with older age being the main risk for advanced neoplasia. Delaying onset of colonoscopy or lengthening surveillance intervals could be a more efficient use of resources in this population.

Reduced gastrointestinal-related hospitalisation costs following rescheduling of over-the-counter codeine-containing compound analgesics in Australia: results of a single hospital audit in South Australia.

BACKGROUND: Codeine-containing compound analgesics (CCCAs) are associated with dependence and, when taken in excess, significant risks of harm. A previous audit showed significant costs related to admissions for gastrointestinal (GI) complications of CCCA. Based on this and other evidence of harm, the Australian Therapeutic Goods Administration changed CCCAs to prescription only in 2018. AIMS: We aimed to identify the costs associated with codeine-related GI complications and whether the schedule change in 2018 led to a reduced clinical and financial strain on the health care system. METHODS: We conducted an audit of GI admissions and associated costs of CCCAs at a tertiary teaching hospital in Adelaide between 2016 and 2020. Patients were grouped by 2-year time periods before (group 1) and following (group 2) schedule change. Costs for the index presentation were multiplied for subsequent presentations. Costs and outcomes were compared for groups (standard statistics; P value < 0.05 significant.) RESULTS: Three hundred forty patients (group 1, n = 164; group 2, n = 119) were identified, with the majority of these admitted due to nonsteroidal anti-inflammatory drugs (NSAIDs) only. For CCCAs (NSAID-containing), the same patients were admitted repeatedly with a reduction from 31 to eight admissions (P = 0.005), following rescheduling. The total cost of CCCA admissions was reduced from AU$ 561 691 for group 1 to AU$ 261 764 for group 2 (P < 0.001). CONCLUSIONS: Australian rescheduling of CCCAs in 2018 resulted in a reduction in hospital admissions and costs related to GI complications. The cost savings, even in a single hospital department, were substantial.

Distension contraction plots of pharyngeal/esophageal peristalsis: next frontier in the assessment of esophageal motor function.

Esophageal peristalsis consists of initial inhibition (relaxation) followed by excitation (contraction), both of which move sequentially in the aboral direction. Initial inhibition results in receptive relaxation and bolus-induced luminal distension, which allows propulsion by the contraction with minimal resistance to flow. Similar to the contraction wave, luminal distension has unique waveform characteristics in normal subjects; both are modulated by bolus volume, bolus viscosity, and posture, suggesting a possible cause-and-effect relationship between the two. Distension contraction plots in patients with dysphagia with normal bolus clearance [high-amplitude esophageal contractions (HAECs), esophagogastric junction outflow obstruction (EGJOO), and functional dysphagia (FD)] reveal two major findings: 1) unlike normal subjects, there is luminal occlusion distal to bolus during peristalsis in certain patients, i.e., with type 3 achalasia and nonobstructive dysphagia; and 2) bolus travels through a narrow lumen esophagus during peristalsis in patients with HAECs, EGJOO, and FD. Aforementioned findings indicate a relative dynamic obstruction to the bolus flow during peristalsis and reduced distensibility of esophageal wall in the bolus segment of the esophagus. We speculate that a normal or supernormal contraction wave pushing bolus against resistance is the mechanism of dysphagia sensation in significant number of patients. Representations of distension and contraction, combined with objective measures of flow timing and distensibility are complementary to the current scheme of classifying esophageal motility disorders based solely on the characteristics of contraction phase of peristalsis. Better understanding of the distensibility of the bolus-containing segment of the esophagus during peristalsis will lead to the development of novel medical and surgical therapies in the treatment of dysphagia in significant number of patients.

Evaluation of oropharyngeal deglutitive pressure dynamics in patients with Parkinson's disease.

In Parkinson's disease (PD), oropharyngeal dysphagia is common and clinically relevant. The neurophysiology of dysphagia in PD is complex and incompletely understood. The aim of the study was to determine the changes in oropharyngeal deglutitive pressure dynamics in PD and to correlate these with clinical characteristics including dysphagia and PD severity. In prospective consecutive series of 64 patients with PD [mean age: 66.9 ± 8.3 (SD)], we evaluated dysphagia severity clinically as well as with Sydney Swallow Questionnaire (SSQ) and Swallow Quality-of-Life Questionnaire (SWAL-QOL). PD severity was assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). We used high-resolution pharyngeal impedance manometry (HRPIM) to objectively evaluate swallow function and compared data from 23 age-matched healthy controls [mean age 62.3 ± 9.1 (SD)]. Metrics assessed were upper esophageal sphincter (UES), integrated relaxation pressure (IRP), relaxation time (RT), maximum opening (MaxAdm), and pharyngeal intrabolus pressure (IBP) and pharyngeal contractility (PhCI). Mean MDS-UPDRS score was positively associated with dysphagia severity on SSQ and SWAL-QOL. HRPIM in PD compared with controls showed impaired UES relaxation parameters, with shorter RT, and elevated IRP and IBP. MaxAdm was not affected. The overall pharyngeal contractility was significantly higher in PD. Only the IBP and IRP were associated with PD severity and only IBP was significantly associated with dysphagia severity. UES dysfunction leading to increased flow resistance is common in patients with PD and correlates with dysphagia severity. Increased flow resistance may suggest impaired UES relaxation and/or impaired neuromodulation to bolus volume.NEW & NOTEWORTHY In Parkinson's disease, objective assessment of swallow function with high-resolution impedance manometry identifies upper esophageal sphincter dysfunction leading to increased flow resistance.

Faecal immunochemical test mitigates risk of delayed colonoscopy in people with elevated risk of colorectal neoplasia.

BACKGROUND AND AIM: Surveillance colonoscopies may be delayed because of pressure on resources, such as the COVID-19 pandemic. This study aimed to determine whether delayed surveillance colonoscopy increases the risk for advanced neoplasia and whether interval screening with faecal immunochemical tests (FITs) and other known risk factors can mitigate this risk. METHODS: A retrospective cohort study of individuals undergoing surveillance colonoscopy for personal or family history of colorectal neoplasia was being provided with FIT between colonoscopies. Colonoscopy ≥ 6 months after the guideline-recommended interval was considered "delayed." Individuals were stratified based on prime colonoscopy findings to nonneoplastic findings, non-advanced adenoma, and advanced adenoma. The relative risk (RR) for developing advanced neoplasia was determined using a robust multivariable modified Poisson regression. RESULTS: Of 2548 surveillance colonoscopies, 1457 (57.18%) were delayed. Prior advanced adenoma, older age (> 60 years) and nonparticipation in interval FIT were associated with increased risk for advanced neoplasia (P < 0.05). There was a trend to increased risk in those with prior advanced adenoma with an increasing colonoscopy delay (P trend = 0.01). In participants who did not complete interval FIT and having advanced adenoma in the prime colonoscopy, risk of advanced neoplasia was 2.48 times higher (RR = 2.48, 95% confidence interval: 1.20-5.13) in participants who had beyond 2 years of delayed colonoscopy compared with those with on-time colonoscopy. Colonoscopy delay did not increase the risk of advanced neoplasia in participants with negative interval FIT results. CONCLUSION: Surveillance colonoscopy can be safely extended beyond 6 months in elevated colorectal cancer risk patients who do not have prior advanced adenoma diagnosis, particularly if interval FIT is negative.

Patient attitudes towards changes in colorectal cancer surveillance: An application of the Health Belief Model.

OBJECTIVE: This is to determine whether health beliefs regarding colorectal cancer (CRC) screening could predict discomfort with a change to CRC surveillance proposing regular faecal immunochemical tests (FIT) instead of colonoscopy. METHODS: Eight hundred individuals enrolled in a South Australian colonoscopy surveillance programme were invited to complete a survey on surveillance preferences. Responses were analysed using binary logistic regression predicting discomfort with a hypothetical FIT-based surveillance change. Predictor variables included constructs based on the Health Belief Model: perceived threat of CRC, perceived confidence to complete FIT and colonoscopy (self-efficacy), perceived benefits from current surveillance and perceived barriers to FIT and colonoscopy. RESULTS: A total of 408 participants (51%) returned the survey (complete data n = 303; mean age 62 years, 52% male). Most participants (72%) were uncomfortable with FIT-based surveillance reducing colonoscopy frequency. This attitude was predicted by a higher perceived threat of CRC (OR = 1.03 [95% CI 1.01-1.04]), higher colonoscopy self-efficacy (OR = 1.34 [95% CI 1.13-1.59]) and lower perceived barriers to colonoscopy (OR = 0.92 [95% CI 0.86-0.99]). CONCLUSIONS: Health beliefs regarding colonoscopy and perceived threat of CRC may be important to consider when changing CRC surveillance protocols. If guideline changes were introduced, these factors should be addressed to provide patients reassurance concerning the efficacy of the alternative protocol.

Effects of remifentanil on pharyngeal swallowing and esophageal motility: no impact of different bolus volumes and partial antagonism by methylnaltrexone.

Remifentanil impairs swallowing, and disturbed accommodation to bolus volume may be one of the underlying causes. It is not fully understood whether remifentanil-induced swallowing dysfunction is mediated by peripheral or central mechanisms. So, this study aimed to investigate if remifentanil-induced swallowing dysfunction is dependent on the bolus volume and whether the effect of remifentanil could be counteracted by methylnaltrexone, a peripherally acting opioid antagonist. Nineteen healthy volunteers were included in this double-blinded, randomized, placebo-controlled, crossover study. Study participants received target-controlled remifentanil infusions and placebo infusions in a randomized order. Methylnaltrexone was administered by intravenous injection of doses of 0.3 mg/kg. Recordings of pressure and impedance data were acquired using a combined manometry and impedance solid-state catheter. Data were analyzed from three series of bolus swallows, baseline, during study medication exposure, and 15 min after methylnaltrexone. Remifentanil induced significant effects on multiple pharyngeal and esophageal function parameters. No significant differences in remifentanil-induced swallowing dysfunction related to different bolus volumes were found. Pharyngeal effects of remifentanil were not significantly counteracted by methylnaltrexone, whereas on the distal esophageal level, effects on distension pressures were counteracted. Changes in pharyngeal and esophageal pressure flow variables were consistent with previous results on remifentanil-induced swallowing dysfunction and uniform across all bolus volumes. The effects of remifentanil on the pharyngeal level and on the proximal esophagus appear to be predominantly centrally mediated, whereas the effects of remifentanil on the distal esophagus may be mediated by both central and peripheral mechanisms.NEW & NOTEWORTHY In this randomized controlled trial, we used the "Swallow Gateway" online platform to analyze the effects of remifentanil on pharyngeal and esophageal swallowing. It is not fully understood whether remifentanil-induced swallowing dysfunction is mediated by peripheral or central mechanisms. By using methylnaltrexone, we demonstrated that effects of remifentanil on pharyngeal swallowing were predominantly centrally mediated, whereas its effects on the distal esophagus may be mediated by both central and peripheral mechanisms.

Modulation of pharyngeal swallowing by bolus volume and viscosity.

Oropharyngeal swallowing involves complex neuromodulation to accommodate changing bolus characteristics. The pressure events during deglutitive pharyngeal reconfiguration and bolus flow can be assessed quantitatively using high-resolution pharyngeal manometry with impedance. An 8-French solid-state unidirectional catheter (32 pressure sensors, 16 impedance segments) was used to acquire triplicate swallows of 3 to 20 ml across three viscosity levels using a Standardized Bolus Medium (SBMkit) product (Trisco, Pty. Ltd., Australia). An online platform (https://swallowgateway.com/; Flinders University, South Australia) was used to semiautomate swallow analysis. Fifty healthy adults (29 females, 21 males; mean age 46 yr; age range 19-78 yr old) were studied. Hypopharyngeal intrabolus pressure, upper esophageal sphincter (UES) maximum admittance, UES relaxation pressure, and UES relaxation time revealed the most significant modulation effects to bolus volume and viscosity. Pharyngeal contractility and UES postswallow pressures elevated as bolus volumes increased. Bolus viscosity augmented UES preopening pressure only. We describe the swallow modulatory effects with quantitative methods in line with a core outcome set of metrics and a unified analysis system for broad reference that contributes to diagnostic frameworks for oropharyngeal dysphagia.NEW & NOTEWORTHY The neuromodulation of the healthy oropharyngeal swallow response was described in relation to bolus volume and viscosity challenges, using intraluminal pressure and impedance topography methods. Among a wide range of physiological measures, those indicative of distension pressure, luminal opening, and flow timing were most significantly altered by bolus condition, and therefore can be considered to be potential markers of swallow neuromodulation. The study methods and associated findings inform a diagnostic framework for swallow assessment in patients with oropharyngeal dysphagia.

The influence of the surveillance time interval on the risk of advanced neoplasia after non-advanced adenoma removal.

OBJECTIVES: To investigate the incidence of advanced neoplasia (colorectal cancer or advanced adenoma) at surveillance colonoscopy following removal of non-advanced adenoma; to determine whether the time interval before surveillance colonoscopy influences the likelihood of advanced neoplasia. DESIGN: Retrospective cohort study. SETTING, PARTICIPANTS: Patients enrolled in a South Australian surveillance colonoscopy program with findings of non-advanced adenoma during 1999-2016 who subsequently underwent surveillance colonoscopy. MAIN OUTCOME MEASURES: Incidence of advanced neoplasia at follow-up surveillance colonoscopy. RESULTS: Advanced neoplasia was detected in 169 of 965 eligible surveillance colonoscopies (18%) for 904 unique patients (median age, 62.0 years; interquartile range [IQR], 54.0-69.0 years), of whom 570 were men (59.1%). The median interval between the initial and surveillance procedures was 5.2 years (IQR, 4.4-6.0 years; range, 2.0-14 years). Factors associated with increased risk of advanced neoplasia at follow-up included age (per year: odds ratio [OR], 1.03; 95% CI, 1.01-1.05), prior history of adenoma (OR, 1.48; 95% CI, 1.01-2.15), two non-advanced adenomas identified at baseline procedure (v one: OR, 1.74; 95% CI, 1.18-2.57), and time to surveillance colonoscopy (OR, 1.21; 95% CI, 1.08-1.37). The estimated incidence of advanced neoplasia was 19% five years after non-advanced adenoma removal, and 30% at ten years. CONCLUSIONS: Increasing the surveillance colonoscopy interval beyond five years after removal of non-advanced adenoma increases the risk of detection of advanced neoplasia at follow-up colonoscopy.

Features associated with high-risk sessile serrated polyps at index and follow-up colonoscopy.

BACKGROUND AND AIM: Clinically significant serrated polyps are precursors of colorectal cancers, with features considered high risk including size ≥10 mm, dysplasia, and presence of synchronous conventional adenoma. While these features have been described in cohorts undergoing screening colonoscopy, there is little information regarding the prevalence and patient characteristics associated with high-risk sessile serrated polyps (SSPs) in those undergoing surveillance colonoscopy. METHODS: Polyp pathology at the index and first follow-up colonoscopy performed between 2004 and 2019 were examined in patients enrolled in a surveillance program because of an index finding of adenoma and/or SSP. Demographics and pathology features for SSP were compared between the colonoscopies. RESULTS: Of 6297 patients undergoing index colonoscopy, 2035 underwent follow-up colonoscopy after 3.3 years (interquartile range 2.1-4.8 years). The proportion with SSP decreased from 7.6% at index to 5.0% at follow-up (P < 0.001); however, the proportion of SSPs that were considered high risk was not different between the colonoscopies (62.8% vs 62.4%). Female gender was associated with the presence of high-risk SSP at index colonoscopy (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.28-2.06), while age ≥75 years (OR 3.38, 95% CI 1.67-6.81) and previous high-risk SSP (OR 9.40, 95% CI 4.23-20.88) were independently associated with high-risk SSP at follow-up. CONCLUSIONS: The prevalence of SSP falls by one-third at first follow-up colonoscopy although the proportion of SSP with high-risk features remains the same. While females were more likely to have a high-risk SSP at the index colonoscopy, those at greatest risk for high-risk SSP at follow-up colonoscopy were age >75 years and an index high-risk SSP.

Changes in specific esophageal neuromechanical wall states are associated with conscious awareness of a solid swallowed bolus in healthy subjects.

Esophageal neuromechanical wall states are the physical manifestations of circular muscle inhibition and contraction resulting from neural inputs and leading to bolus propulsion. A novel method infers esophageal neuromechanical wall states through simultaneous determination of pressure and diameter in vivo using impedance manometry. We hypothesized that changes in esophageal neuromechanical wall states relate to conscious awareness of esophageal bolus passage ("bolus perception"). Seven healthy participants were selected for perception of solid bolus passage and were compared with seven healthy participants with no conscious awareness of solid bolus passage. Participants were studied using impedance manometry (MMS Solar, Unisensor, 20 Hz). Subjects swallowed ten 5-ml liquid and ten 2-cm square saline-soaked bread boluses and rated bolus perception using a visual analog scale. Esophageal neuromechanical wall states were calculated and analyzed. Proportions of time spent in states with and without luminal distension were compared using a two-proportions Z-test. Bolus perception was associated with neuromechanical wall states corresponding to luminal distension more frequently than matching states without distension in the proximal esophagus (P < 0.001) and transition zone (P < 0.001), whereas there were no differences for the distal esophagus. In healthy volunteers, perceived swallows relate to changes in esophageal neuromechanical wall states in the proximal esophagus. We postulate that these changes relate to bolus retention and summation of active and passive wall tension activating intramural tension receptors.NEW & NOTEWORTHY This study explores esophageal neuromechanical wall states derived from changes in pressure and impedance-derived distension in relation to conscious awareness of esophageal solid bolus transit in healthy volunteers. There are increases in neuromechanical wall states indicative of esophageal distension in healthy volunteers with conscious awareness of bolus transit as compared with unaware individuals. Bolus-based esophageal distension is postulated as a mechanism for esophageal symptoms such as dysphagia.

Older age, symptoms, or anemia: Which factors increase colorectal cancer risk with a positive fecal immunochemical test?

BACKGROUND AND AIM: Fecal immunochemical tests (FIT) are used to screen asymptomatic individuals aged 50-74 years for colorectal cancer (CRC) within the Australian screening program. Gastrointestinal symptoms or iron deficiency anemia (IDA) may also drive primary care physicians to request a FIT. This study aimed to examine factors that may increase neoplasia risk associated with a positive FIT, specifically age, gastrointestinal symptoms, or IDA. METHODS: A retrospective audit was performed on colonoscopies performed in a single hospital in South Australia for a positive FIT (from all referral sources) between 2014 and 2017. Patients aged < 50 years, or who had a colonoscopy in the preceding 5 years, were excluded. A subgroup (n = 198) was evaluated to assess whether age ≥ 75 years, symptoms, or IDA, as well as other demographics, comorbidities, and medications, were associated with risk of neoplasia. Features found to be associated with risk for CRC or high-risk adenoma were examined in the entire cohort using multivariate analysis. RESULTS: Colonoscopies (750/4221, 17.8%) were completed in patients ≥ 50 years for a positive FIT. Of these, 7.6% (n = 57) also had gastrointestinal symptoms, 5.5% (n = 41) IDA, and 13.1% (n = 98) were ≥ 75 years. At colonoscopy, 2.8% (n = 21) were diagnosed with CRC and 23.2% (n = 174) with high-risk adenoma. CRC was more prevalent in ≥ 75 years compared with 50-74 years (7.1% vs 2.1%, P = 0.005), and associated with symptoms (15.8% vs 1.7%, P < 0.001), and IDA (14.6% vs 2.1%, P < 0.001). Multivariate analysis showed that IDA (odds ratio 7.68, P < 0.001) and symptoms (odds ratio 10.37, P < 0.001), but not age, were independent risk factors for CRC. CONCLUSION: The presence of gastrointestinal symptoms or IDA, independent of age, is associated with an increased risk for CRC following a positive FIT.