Constipated patients with functional defecatory disorder have secondary rectal hyposensitivity due to altered rectal biomechanics.

BACKGROUND AND AIM: Rectal hyposensitivity (RH) is common in constipation and often coexists with functional defecatory disorder (FDD). Rectal sensory thresholds are routinely evaluated with the anorectal manometry probe; however, the gold standard for the assessment of rectal sensitivity is with a barostat, use of which is limited by time constraints and availability. A novel rapid barostat bag (RBB) may facilitate measurements of rectal sensitivity. The aim is to evaluate the relationship between RH (measured by the RBB) and FDD (defined as any minor disorder of rectoanal coordination by the London classification) in constipated patients. METHODS: Consecutive constipated patients referred for anorectal function testing underwent anorectal manometry with the 3D-HDAM probe as well as rectal sensation testing with the RBB pump. RH was defined by volume to first sensation >30%, urge to defecate >80%, or discomfort >100% (normalized to rectal capacity). RESULTS: Fifty-three percent of constipated patients had RH. Patients with FDD had a significantly increased volume to first sensation (134.5 mL vs 102.0, P = 0.02), urge to defecate (187.0 mL vs 149.0, P = 0.04), and rectal capacity (253.5 mL vs 209.0, P = 0.04) compared to constipated patients without FDD. There was no difference in normalized sensory thresholds (percent of rectal capacity) nor the prevalence of hyposensitivity to each sensory threshold nor overall hyposensitivity. CONCLUSION: Patients with FDD, when measured with the RBB, have increased sensory thresholds on volumetric distension, but RH was not observed when sensory threshold volume were normalized to rectal capacity. This may reflect "secondary" RH due to altered rectal biomechanics.

Epidemiologic Burden and Treatment of Chronic Symptomatic Functional Bowel Disorders in the United States: A Nationwide Analysis.

BACKGROUND & AIMS: Functional bowel disorders (FBDs) are the most common gastrointestinal problems managed by physicians. We aimed to assess the burden of chronic symptomatic FBDs on ambulatory care delivery in the United States and evaluate patterns of treatment. METHODS: Data from the National Ambulatory Medical Care Survey were used to estimate annual rates and associated costs of ambulatory visits for symptomatic irritable bowel syndrome, chronic functional abdominal pain, constipation, or diarrhea. The weighted proportion of visits associated with pharmacologic and nonpharmacologic (stress/mental health, exercise, diet counseling) interventions were calculated, and predictors of treatment strategy were evaluated in multivariable multinomial logistic regression. RESULTS: From 2007-2015, approximately 36.9 million (95% CI, 31.4-42.4) weighted visits in patients of non-federally employed physicians for chronic symptomatic FBDs were sampled. There was an annual weighted average of 2.7 million (95% CI, 2.3-3.2) visits for symptomatic irritable bowel syndrome/chronic abdominal pain, 1.0 million (95% CI, 0.8-1.2) visits for chronic constipation, and 0.7 million (95% CI, 0.5-0.8) visits for chronic diarrhea. Pharmacologic therapies were prescribed in 49.7% (95% CI, 44.7-54.8) of visits compared to nonpharmacologic interventions in 19.8% (95% CI, 16.0-24.2) of visits (P < .001). Combination treatment strategies were more likely to be implemented by primary care physicians and in patients with depression or obesity. The direct annual cost of ambulatory clinic visits alone for chronic symptomatic FBDs is approximately US$358 million (95% CI, 233-482 million). CONCLUSIONS: The management of chronic symptomatic FBDs is associated with considerable health care resource use and cost. There may be an opportunity to improve comprehensive FBD management because fewer than 1 in 5 ambulatory visits include nonpharmacologic treatment strategies.

Peroral endoscopic myotomy (POEM) for complex achalasia and the POEM difficulty score.

BACKGROUND: Peroral endoscopic myotomy (POEM) for achalasia is technically challenging to carry out in patients with type III, multiple prior treatments, prior myotomy, and sigmoid type. Herein, we present a series of consecutive patients with complex achalasia and introduce the POEM difficulty score (PDS). AIM: To demonstrate the application and discuss the utility of PDS and present the feasibility, safety, and efficacy of POEM in complex achalasia patients. METHODS: Forty consecutive POEM were carried out with 28 meeting the criteria for complex achalasia. Primary outcome was clinical success (Eckardt score ≤3) at a minimum of 3 months follow-up. Secondary outcomes included adverse events, procedural velocity and PDS. RESULTS: Twenty-eight complex and 12 non-complex POEM procedures were carried out with 100% and 92% clinical success, respectively, without any major adverse events with a median follow up of 15 months (complex) and 8 months (non-complex). Mean velocities for non-complex, type III, prior myotomy, ≥4 procedures and sigmoid type were as follows: 4.4 ± 1.6, 4.8 ± 1.5, 5.9 ± 2.2, 6.9 ± 2.2 and 8.2 ± 3.2 min/cm, respectively. Median PDS for non-complex, type III, prior myotomy, ≥4 treatments and sigmoid type were 1 (0-3), 2 (0-4), 2.5 (1-6), 3 (2-6) and 3.5 (1-6), respectively. PDS was shown to correlate well with procedural velocity with a correlation coefficient of 0.772 (Spearman's P < 0.001). CONCLUSIONS: PDS identifies the factors that contribute to challenging POEM procedures and correlates well with procedural velocity. The order of increasing difficulty of POEM in complex achalasia appears to be type III, prior myotomy, ≥4 treatments and sigmoid type.

Pancreatic Adenosquamous Carcinoma Presenting as a Gastric Lesion.

Pancreatic adenosquamous carcinoma, an uncommon subtype of pancreatic adenocarcinoma, is characterized by an aggressive course and poor prognosis, with the only method of cure being surgical resection at the time of diagnosis. It is a complex condition, as it presents nonspecifically and remains indistinguishable from pancreatic adenocarcinoma without imaging techniques despite its aggressive nature. We report an atypical case of pancreatic adenosquamous carcinoma, presenting with marked anemia, found on endoscopy to have a gastric mass. This is of interest to readers as a reminder that pancreatic cancers may present with gastric invasion and should remain on the differential diagnosis for gastric lesions.

Correction to: Pancreatic Adenosquamous Carcinoma Presenting as a Gastric Lesion.

[This corrects the article DOI: 10.14309/crj.0000000000001319.].

The Relationship between Upper Esophageal Sphincter Manometry Function and Esophageal Motility Disorders.

OBJECTIVE: High-resolution manometry (HRM) provides measures of esophageal function which are used to classify esophageal motility disorders based on the Chicago Classification system. Upper esophageal sphincter (UES) measures are obtained from HRM, but are not included in the classification system, rendering the relationship between UES measures and esophageal motility disorders unclear. Furthermore, changes in the acceptable amount of esophageal dysfunction between versions of this classification system has created controversy. The objective of this study was to determine the relationship between UES measures and esophageal function. STUDY DESIGN: Cross-sectional study. SETTING: Referral centre. METHODS: HRM studies from the Calgary Gut Motility Center were reviewed for UES mean basal pressure, mean residual pressure, relaxation time-to-nadir, relaxation duration, and recovery time. Patients were grouped by number of failed swallows according to different iterations of the Chicago Classification: 0 to 4 (Group 1), 5 to 7 (Group 2), and 8 to 10 (Group 3). RESULTS: 2114 patients (65.1% female, median age 56 y) were included. There were significant increases in UES mean basal pressure (P < .001), mean residual pressure (P < .001), relaxation duration (P < .001), and recovery time (P < .001) between groups. Positive correlations existed between number of failed swallows and UES mean basal pressure (r = 0.143; P < .001), mean residual pressure (r = 0.201; P < .001), relaxation duration (r = 0.145; P < .001), and recovery time (r = 0.168; P < .001). CONCLUSIONS: Differences in UES measures exist among patients with failed swallows, with a positive correlation between UES dysfunction and increasing dysmotility. Our findings illustrate that UES measures are closely related to esophageal function, and that even minor esophageal dysfunction is related to UES dysfunction.

Esophageal motility in systemic sclerosis before and after autologous hematopoietic cell transplantation.

INTRODUCTION: Systemic sclerosis (SSc) is associated with esophageal dysmotility. Autologous hematopoietic cell transplantation (HCT) results in improvement of skin tightness and lung function. Whether esophageal motility improves after HCT is unknown. METHODS: Esophageal motility was studied using high-resolution esophageal manometry in 21 SSc patients before and at multiple time points after autologous HCT. Median posttransplant follow-up was 2 years (range, 6 months to 5 years). RESULTS: Prior to HCT, all 21 patients had abnormal motility-10 (48%) had unmeasurable and 11 (52%) had measurable peristalsis. Manometric diagnosis in the former 10 patients was "absent contractility" and in the latter 11 patients "ineffective esophageal motility (IEM)." After HCT, among the 10 patients with absent contractility, 9 continued to have absent contractility and one demonstrated weak measurable peristalsis. Of the 11 patients with IEM, 5 experienced SSc relapse, and 2 out of these 5 patients developed absent contractility. Among the 6 non-relapsed patients, 4 continued to have IEM, and 2 developed normal motility. CONCLUSIONS: HCT appears to have no beneficial effect on motility in patients with unmeasurable peristalsis. In patients with measurable peristalsis, HCT appears to stabilize and in some normalize motility, unless relapse occurs. Key Points • In patients with systemic sclerosis, esophageal dysmotility is a significant contributor to morbidity and so far, there has been no data describing the effects of hematopoietic cell transplantation on esophageal motility. • Our work demonstrated that in patients with systemic sclerosis and unmeasurable esophageal peristalsis prehematopoietic cell transplantation, there was no measurable beneficial effect of transplantation on esophageal motility. • In patients with systemic sclerosis and measurable peristalsis prehematopoietic cell transplantation, esophageal motility stabilized, except in relapsed patients.

Manometric parameters, when measured with the 3-dimensional high-definition anorectal manometry probe, poorly predict prolonged balloon expulsion time.

BACKGROUND: There are little data evaluating the performance of the 3-dimensional high-definition anorectal manometry (3D-HDAM) system in the diagnosis of dyssynergic defecation. Physical properties of the thicker, rigid, 3D-HDAM probe may have implications on the measurements of anorectal pressures. AIM: Our aim was to compare 3D-HDAM to balloon expulsion test and magnetic resonance (MR) defecography. METHODS: Consecutive constipated patients referred for anorectal function testing at the Calgary Gut Motility Centre (Calgary, Canada) between 2014 and 2019 were assessed. All patients underwent anorectal manometry with the 3D-HDAM probe, and a subset underwent BET or MR defecography. Anorectal manometric variables were compared between patients who had normal and abnormal BET. RESULTS: Over the study period, 81 patients underwent both 3D-HDAM and BET for symptoms of constipation. 52 patients expelled the balloon within 3 minutes. Patients with abnormal BET had significantly lower rectoanal pressure differential (RAPD) (-61 vs. -31 mmHg for normal BET, p = 0.03) and defecation index (0.29 vs. 0.56, p = 0.03). On logistic regression analysis, RAPD (OR: 0.99, 95% CI: 0.97-0.99, p = 0.03) remained a negative predictor of abnormal BET. On ROC analysis, RAPD had an AUC of 0.65. There was good agreement between dyssynergic patterns on 3D-HDAM and defecographic evidence of dyssynergia (sensitivity 80%, specificity 90%, PLR 9, NLR 0.22, accuracy 85%). CONCLUSIONS: Manometric parameters, when measured with the 3D-HDAM probe, poorly predict prolonged balloon expulsion time. RAPD remains the best predictor of prolonged balloon expulsion time. The 3D-HDAM probe may not be the ideal tool to diagnose functional defecatory disorders.

Cannabinoid hyperemesis syndrome in North America: evaluation of health burden and treatment prevalence.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use. AIMS: To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021). RESULTS: Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p < 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group. CONCLUSION: Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.

Hematopoietic Cell Transplantation for Systemic Sclerosis-A Review.

Systemic sclerosis (SSc) is an autoimmune, multi-organ, connective tissue disease associated with significant morbidity and mortality. Conventional immunosuppressive therapies demonstrate limited efficacy. Autologous hematopoietic stem cell transplantation (HCT) is more efficacious but carries associated risks, including treatment-related mortality. Here, we review HCT as a treatment for SSc, its efficacy and toxicity in comparison to conventional therapies, and the proposed mechanisms of action. Furthermore, we discuss the importance of and recent developments in patient selection. Finally, we highlight the knowledge gaps and future work required to further improve patient outcomes.

The Canadian POEM Experience: The First 50 Patients.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM) has emerged as a less invasive technique for performing myotomy in patients with achalasia. This study aims to assess the safety and efficacy of POEM in a Canadian tertiary care center. METHODS: All consecutive patients who underwent POEM between March 2016 and May 2018 at a tertiary center were included. The primary outcome of the study was clinical success rate of POEM defined as a post-POEM Eckardt score ≤3 at ≥3 months. Adverse events were recorded according to the Clavien-Dindo grading system. RESULTS: A total of 50 consecutive patients underwent 51 POEM procedures with a mean procedure length of 85.6 ± 29.6 min. Post-POEM Eckardt scores of ≤3 at ≥3 months was achieved in 98% of patients. The incidence of pathologic reflux post-poem was 23%. The median length of hospital stay was 1 day. No major adverse events occurred. INTERPRETATION: POEM is a safe and effective procedure for the treatment of achalasia. At a median follow-up of 19.5 months, 98% of patients had sustained clinical response (Eckardt score ≤3).

Prucalopride in diabetic and connective tissue disease-related gastroparesis: Randomized placebo-controlled crossover pilot trial.

BACKGROUND: Gastroparesis, defined by delayed gastric emptying in the absence of mechanical outlet obstruction, is a frequent neuropathic complication of diabetes mellitus, and effective treatments are lacking. Prucalopride is a pan-gut prokinetic with selective agonist effects on serotonin 5-HT4 receptors in the gut. This study aimed to assess the effect of prucalopride 4 mg daily on Gastroparesis Cardinal Symptom Index (GCSI), meal-related symptom score (MRSS), and gastric emptying rate in diabetic or connective tissue disease (CTD)-related gastroparesis patients. METHODS: This was a double-blind crossover trial of four-week treatment periods with prucalopride or placebo divided by two weeks of washout. GSCI, MRSS, gastric emptying scintigraphy, PAGI-SYM, and PAGI-QoL were assessed at baseline and the end of each treatment period. Daily bowel movement (BM) frequency and gastrointestinal symptoms were recorded in each period. KEY RESULTS: Fifteen gastroparesis patients (13 diabetic, 2 CTD) were enrolled. GCSI scores were lower than baseline but not different between treatment arms. MRSS scores over time or cumulative score were not significantly different between groups. Gastric emptying was more rapid in the prucalopride treatment period, with mean four-hour meal retention of 22 ± 6% in PRU period vs 40 ± 9% in the placebo period (P = 0.05). Weekly BM frequency was significantly higher in prucalopride than placebo periods (10.5 ± 1.8 vs 7.5 ± 0.8, P < 0.0001). Perception of weight loss was higher in patients on prucalopride. Analysis of diabetic gastroparesis (n = 13) population did not change the conclusions. CONCLUSION AND INFERENCE: Prucalopride at 4 mg accelerates gastric emptying and bowel movement frequency but does not appear to ameliorate gastroparesis or meal-related symptoms in this study.

Cannabis in Gastroenterology: Watch Your Head! A Review of Use in Inflammatory Bowel Disease, Functional Gut Disorders, and Gut-Related Adverse Effects.

PURPOSE OF REVIEW: To review recent clinical evidence surrounding the use of cannabinoids and cannabis in gastrointestinal diseases, particularly inflammatory bowel disease (IBD) and functional gut disorders. A second aim is to evaluate the current status of gastrointestinal related adverse effects which have been linked to cannabis use, specifically cannabis hyperemesis syndrome (CHS) and acute pancreatitis. RECENT FINDINGS: Observational and prospective studies suggest that cannabinoids improve IBD symptoms. Small prospective clinical trials have not shown any effects on objective inflammatory findings, other than one recent paper in ulcerative colitis, in abstract form only, which suggests endoscopic improvement. Short duration mechanistic studies in functional gut disorders suggest cannabinoids may attenuate gastric emptying and slow colonic motility but appear to have less effect on sensory thresholds in the gut. SUMMARY: In general, while mostly uncontrolled data suggests cannabis may improve symptoms in IBD (and to a lesser degree functional gut disorders), this is not likely due to any substantial anti-inflammatory effect. Much remains unknown about CHS etiology and complete abstinence from cannabinoids remains the generally accepted treatment strategy. Population-based studies do not suggest that cannabis use is related to acute pancreatitis. Further research is certainly warranted.

Gastroesophageal Reflux Disease Is Not Associated With Jackhammer Esophagus: A Case-control Study.

BACKGROUND/AIMS: The pathophysiology of jackhammer esophagus (JE) remains unknown but may be related to gastroesophageal reflux disease or medication use. We aim to determine if pathologic acid exposure or the use of specific classes of medications (based on the mechanism of action) is associated with JE. METHODS: High-resolution manometry (HRM) studies from November 2013 to March 2019 with a diagnosis of JE were identified and compared to symptomatic control patients with normal HRM. Esophageal acid exposure and medication use were compared between groups. Multivariate regression analysis was performed to look for predictors of mean distal contractile integral. RESULTS: Forty-two JE and 127 control patients were included in the study. Twenty-two (52%) JE and 82 (65%) control patients underwent both HRM and ambulatory pH monitoring. Two (9%) JE patients and 14 (17%) of controls had evidence of abnormal acid exposure (DeMeester score > 14.7); this difference was not significant (P = 0.290). Thirty-six (86%) JE and 127 (100%) control patients had complete medication lists. Significantly more JE patients were on long-acting beta agonists (LABA) (JE = 5, control = 4; P = 0.026) and calcium channel blockers (CCB) (JE = 5, control = 3; P = 0.014). Regular opioids (ß = 0.298, P = 0.042), CCB (ß = 0.308, P = 0.035), and inhaled anticholinergics (ß = 0.361, P = 0.049) predicted mean distal contractile integral (R2 = 0.082, F = 4.8; P = 0.003). CONCLUSIONS: Pathologic acid exposure does not appear to be associated with JE. JE patients had increased CCB and LABA use. The unexpected finding of increased LABA use warrants more investigation and may provide support for a cholinergic etiology of JE.

Anticholinergic, anti-depressant and other medication use is associated with clinically relevant oesophageal manometric abnormalities.

BACKGROUND: Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. AIM: To review the effect of existing medication use on high-resolution oesophageal manometry (HRM) in a 'real-world' setting. METHODS: Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22-month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. RESULTS: A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta-agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2-10.8). Odds ratio for anticholinergics, inhaled beta-agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. CONCLUSION: Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.

Reversible Jackhammer esophagus in a patient with a gastric band.

We wish to report a case of Jackhammer esophagus in a patient with laparoscopic gastric band, with confirmed resolution of hypertensive peristalsis on deflation of the band. This finding adds to the growing body of evidence that outlet obstruction plays an important role in the pathophysiology of Jackhammer esophagus, which remains incompletely defined.