Camilleri, Michael

Buffet meal intake was inversely related to the ability to resist the urge to overeat. Factors associated with ingestive behavior significantly correlated with satiety and gastric accommodation. Gastric capacity during fasting is associated with calorie intake to the point of comfortable fullness; factors associated with ingestive behavior are associated with satiety and gastric accommodation.

AbstractBackgroundLipomatosis of nerve (LN) is a complex peripheral nerve disorder characterized by fibrofatty nerve enlargement. MRI of this pathology is pathognomonic and obviates a diagnostic biopsy. Mutation in PIK3CA has been associated with LN cases with nerve‐territory overgrowth which may occur in some cases. We evaluate an association of LN of the sciatic nerve and early‐onset colonic diverticular disease and discuss the potential pathogenesis.MethodsOur institutional database was searched for LN cases. Available information of identified cases was reviewed, and cases with a confirmed diagnosis of LN affecting the lumbosacral plexus and/or sciatic nerve; available MRI of the affected nerve(s); and diverticular disease occurring in the area supplied by the nerve(s) affected by LN were further analyzed. PIK3CA mutation testing was performed on available tissue samples.ResultsWe identified 10 LN cases of lumbosacral plexus and/or sciatic nerve. Of these, three fulfilled our inclusion criteria. All three patients had concomitant colonic diverticular disease, diagnosed at a relatively young age. MRI studies of these cases showed LN involvement of the sacral nerves innervating the sigmoid colon. All three also had abnormal diagnostic workup including various GI tests and evidence of associated nerve‐territory overgrowth. Colonic tissue samples for PIK3CA mutation were negative.ConclusionWhile the pathogenesis of the colonic diverticular disease is increasingly recognized as being multifactorial, our observations are consistent with the potential role of autonomic nervous system dysfunction affecting either the pelvic floor musculature, or the colon itself (or both) in a subset of patients with early‐onset diverticular disease.

Bile acids (BAs) are the central signals in enterohepatic communication, and they also integrate microbiota-derived signals into enterohepatic signaling. The tissue distribution and signaling pathways activated by BAs through natural receptors, farsenoid X receptor and G protein–coupled BA receptor 1 (GPBAR1, also known as Takeda G-coupled receptor 5), have led to a greater understanding of the mechanisms and potential therapeutic agents. BA diarrhea is most commonly encountered in ileal resection or disease, in idiopathic disorders (with presentation similar to functional diarrhea or irritable bowel syndrome with diarrhea), and in association with malabsorption such as chronic pancreatitis or celiac disease. Diagnosis of BA diarrhea is based on 75 Se-homocholic acid taurine retention, 48-hour fecal BA excretion, or serum 7αC4; the latter being a marker of hepatic BA synthesis. BA diarrhea tends to be associated with higher body mass index, increased stool weight and stool fat, and acceleration of colonic transit. Biochemical markers of increased BA synthesis or excretion are available through reference laboratories. Current treatment of BA diarrhea is based on BA sequestrants, and, in the future, it is anticipated that farsenoid X receptor agonists may also be effective. The optimal conditions for an empiric trial with BA sequestrants as a diagnostic test are still unclear. However, such therapeutic trials are widely used in clinical practice. Some national guidelines recommend definitive diagnosis of BA diarrhea over empirical trial.

AbstractThe available COVID‐19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID‐19 pandemic. Local health systems aim to contain the COVID‐19 pandemic and hospitals and health‐care providers rush to provide the capacity for a surge of COVID‐19 patients. However, the short, medium‐term, and long‐term outcomes of patients with gastrointestinal (GI) diseases without COVID‐19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID‐19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health‐care needs of COVID‐19 patients. During the adaptation phase, GI services are calibrated towards a “new normal,” and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long‐term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence‐based decision‐making during the adaptation and consolidation phases.

AbstractObjectiveOrthostatic intolerance (OI) and autonomic dysfunction (AD) are common in adolescents and young adults. Patients experience multisystem symptoms including gastrointestinal (GI), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), or only symptoms of OI (SOI) without significant findings on 70‐degree head‐up tilt testing (HUT). We hypothesize that patients with POTS, OH, and SOI show differences in GI symptoms and motility test and that heart rate (HR) changes on HUT predict severity of GI dysmotility.Study designFrom medical records of patients (<18 years) with OI, we collected demographics, presenting symptoms, GI manifestations, and GI motility testing. Data were compared between the 3 groups (POTS, OH, and SOI). We assessed changes in HR on HUT with changes on GI motility evaluation.ResultsTwo hundred twenty‐nine patients were included (73% females). Abdominal pain (65%), nausea (49%), vomiting (18%), and constipation (24%) were the most common GI symptoms. In patients who had motility evaluation, there were 27% (53/193) with delayed gastric emptying (GE) at 4 hours, 35% (32/92) with delayed colonic transit (CT), 55% (17/31) with reduced gastric accommodation (GA), and 75% (21/28) with dyssynergic defecation (DD). Among 100 POTS, 34 OH, and 95 SOI patients, no significant differences in GI symptoms or motility tests were identified and HR changes on HUT were not associated with changes on motility tests.ConclusionGI symptoms are frequent in adolescents with OI and are associated with delayed GE, reduced GA, delayed CT, and presence of DD.

SummaryBackgroundWhen opioid‐induced constipation is treated with centrally acting opioid antagonists, there may be opioid withdrawal or aggravation of pain due to inhibition of μ‐opioid analgesia. This led to the development of peripherally acting μ‐opioid receptor antagonists (PAMORAs).AimTo evaluate the efficacy of available PAMORAs and other approved or experimental treatments for relieving constipation in patients with opioid‐induced constipation, based on a systematic review and meta‐analysis of published studies.MethodsA search of MEDLINE, EMBASE and EBM Reviews Cochrane Central Register of Controlled Trials was completed in July 2019 for randomised trials compared to placebo. FDA approved doses or highest studied dose was evaluated. Efficacy was based on diverse endpoints, including continuous variables (the bowel function index, number of spontaneous bowel movements and stool consistency based on Bristol Stool Form Scale), or responder analysis (combination of >3 spontaneous bowel movements or complete spontaneous bowel movements plus 1 spontaneous bowel movement or complete spontaneous bowel movements, respectively, over baseline [so‐called FDA endpoints]). Adverse effects evaluated included central opioid withdrawal, serious adverse events, abdominal pain and diarrhoea.ResultsWe included 35 trials at low risk of bias enrolling 13 566 patients. All PAMORAs demonstrated efficacy on diverse patient response endpoints. There was greater efficacy with approved doses of the PAMORAs (methylnaltrexone, naloxegol and naldemidine), with lower efficacy or lower efficacy and greater adverse effects with combination oxycodone with naloxone, lubiprostone and linaclotide.ConclusionsTherapeutic response in opioid‐induced constipation is best achieved with the PAMORAs, methylnaltrexone, naloxegol and naldemidine, which are associated with low risk of serious adverse events.

INTRODUCTION: Bile acid (BA) diarrhea is the cause in ∼26% of chronic unexplained (nonbloody) diarrhea (CUD) based on 75 SeHCAT testing. To assess fecal BA excretion and healthcare utilization in patients with CUD. METHODS: In a retrospective review of 1,071 consecutive patients with CUD who completed 48-hour fecal BA testing, we analyzed the symptoms, diagnostic tests performed, and final diagnoses. RESULTS: After 135 patients were excluded because of mucosal diseases, increased BA excretion was identified in 476 (51%) of the 936 patients with CUD: 29% with selective increase in primary BA and 22% with increased total BA excretion (35% with normal primary BA excretion). There were no differences in demographics, clinical symptoms, or history of cholecystectomy in patients with elevated total or selective primary fecal BA excretion compared with patients with normal excretion. Before the 48-hour fecal BA excretion test was performed, patients completed on average 1.2 transaxial imaging, 2.6 endoscopic procedures, and 1.6 miscellaneous tests/person. Less than 10% of these tests identified the etiology of CUD. Total fecal BAs >3,033 µmol/48 hour or primary BAs >25% had a 93% negative predictive value to exclude mucosal disease. Among patients with increased fecal BA excretion, >70% reported diarrhea improved with BA sequestrant compared with 26% with normal fecal BA excretion. Patients with selective elevation in primary fecal BAs were 3.1 times (95% confidence interval, 1.5–6.63) more likely to respond to BA sequestrant therapy compared with those with elevated total fecal BAs. DISCUSSION: Increased fecal BA excretion is frequent (51%) in patients with CUD. Early 48-hour fecal BA evaluation has the potential to decrease healthcare utilization in CUD.

AbstractBackgroundColonic transit measurement [geometric center (GC) at 24 and 48 hours] identifies slow transit constipation (STC) in patients with chronic constipation.AimTo evaluate the utility of the difference between GC24 and GC48 (Δ48‐24) to identify STC in adults with chronic constipation.MethodsWe reviewed medical records of 250 patients, aged 18‐75 years, who underwent colonic transit by scintigraphy during 1994‐2019 for investigation of chronic constipation. Data collected included demographics, medical and surgical histories, and anorectal manometry. We used colonic transit from 220 healthy controls to identify the 5th percentile for diagnosing STC: 1.3 at 24 hours, and 1.9 at 48 hours. In addition, the 5th percentile for Δ48‐24 was 0.38 for females and 0.29 for males. Data are reported as median and IQR [Q1, Q3]).Key resultsAmong the 250 patients [median age 42.5 years (IQR 30.75, 56), 84% female], based on GC24 < 1.3, 52 (20.8%) had STC (3 males, 49 females); and based on GC48 < 1.9, 28(11.2%) had STC (3 males, 25 females). Colonic transit was normal in 74.8%. In the groups with normal GC24 and GC48, Δ48‐24 identified an additional 32(15.1%) of 212 female patients and 4 (10.5%) of 38 male patients with slow progression of colonic transit between 24 and 48 hours. Among these 36 patients with abnormal Δ48‐24, 13(36.1%) had evidence of rectal evacuation disorder.Conclusions & InferencesΔ48‐24 measurement on scintigraphic colonic transit can identify an additional 9.2% of STC in patients with constipation without rectal evacuation disorder and can help individualize treatment of chronic constipation.