Background Disorders of gastrointestinal (GI) transit and motility are common, and cause either delayed or accelerated transit through the stomach, small intestine or colon, and affect one or more ...regions. Assessment of regional and/or whole gut transit times can provide direct measurements and diagnostic information to explain the cause of symptoms, and plan therapy.
Purpose Recently, several newer diagnostic tools have become available. The American and European Neurogastroenterology and Motility Societies undertook this review to provide guidelines on the indications and optimal methods for the use of transit measurements in clinical practice. This was based on evidence of validation including performance characteristics, clinical significance, and strengths of various techniques. The tests include measurements of: gastric emptying with scintigraphy, wireless motility capsule, and 13C breath tests; small bowel transit with breath tests, scintigraphy, and wireless motility capsule; and colonic transit with radioopaque markers, wireless motility capsule, and scintigraphy. Based on the evidence, consensus recommendations are provided for each technique and for the evaluations of regional and whole gut transit. In summary, tests of gastrointestinal transit are available and useful in the evaluation of patients with symptoms suggestive of gastrointestinal dysmotility, since they can provide objective diagnosis and a rational approach to patient management.
Background Patient‐reported symptom scales are needed to evaluate treatments for gastroparesis. The Gastroparesis Cardinal Symptom Index‐Daily Diary (GCSI‐DD) was developed to assess daily symptoms ...of gastroparesis. This study evaluated the validity and responsiveness of the GCSI‐DD in patients with gastroparesis.
Methods Symptomatic patients were started with a new treatment for gastroparesis. Patients completed the GCSI‐DD each evening during a baseline week and for 8 weeks of treatment. Responders were defined based on patient and clinician global rating of change. Minimal important differences (MID) were estimated based on baseline to 4 week changes in symptoms scores for small improvements.
Key Results Of 69 patients participating, 46 had idiopathic, 19 diabetic, and four postfundoplication gastroparesis. Excellent test–retest reliability was seen for GCSI‐DD scores, and there were significant correlations between GCSI‐DD scores and clinician ratings of symptom severity. Responders to treatment reported improvements in nausea effect size (ES) = 0.42, P < 0.001, postprandial fullness, ES = 0.83, P < 0.001), bloating (ES = 0.34, P < 0.001), early satiety (ES = 0.53, P < 0.001), but lower responses for upper abdominal pain (ES = 0.29), and vomiting (ES = 0.22; P = 0.119). MIDs were 0.55 for nausea, 0.97 for excessive fullness, 0.63 for bloating, 0.77 for postprandial fullness, and 0.30 for abdominal pain. A composite score of four symptoms (Composite‐1; nausea, bloating, excessive fullness, postprandial fullness) had ES of 0.61 and MID of 0.73. Composite‐2 score (nausea, early satiety, bloating, abdominal pain) had a lower ES of 0.47.
Conclusions & Inferences Symptoms of early satiety, nausea, postprandial fullness, and bloating were responsive to treatment for gastroparesis. A composite of these symptoms also demonstrates validity and responsiveness to treatment for gastroparesis, and may represent an acceptable endpoint for evaluating the effectiveness of medical treatments in clinical trials for gastroparesis.
Functional dyspepsia (FD) is a highly prevalent functional bowel disorder. The effects of antidepressant therapy (ADTx) on gastric sensorimotor function in FD patients are poorly understood.
...Determine whether FD and subtypes with abnormalities in gastric function respond differently to ADTx compared to those with normal physiology.
This multicenter, prospective trial randomized FD patients to 12 weeks of amitriptyline (AMI; 50 mg), escitalopram (ESC; 10 mg), or matching placebo. Demographics, symptoms, psychological distress, gastric emptying, and satiation were measured. Gastric accommodation (GA) using single-photon emission computed tomography imaging was performed in a subset of patients. An intent to treat analysis included all randomized subjects. The effect of treatment on gastric emptying was assessed using ANCOVA. A post hoc appraisal of the data was performed categorizing patients according to the Rome III subgrouping (PDS and EPS).
In total, 292 subjects were randomized; mean age=44 yrs. 21% had delayed gastric emptying. Neither antidepressant altered gastric emptying, even in those with baseline delayed gastric emptying. GA increased with ADTx (P=0.02). Neither antidepressant affected the maximal-tolerated volume (MTV) of the nutrient drink test although aggregate symptom scores improved compared to placebo (P=0.04). Patients with the combined EPS-PDS subtype (48%) had a lower MTV on the nutrient drink test compared to the EPS group at baseline (P=0.02). Postprandial bloating improved with both AMI (P=0.03) and ESC (P=0.02).
Amitriptyline (50 mg) improves FD symptoms but does not delay gastric emptying, even in patients with baseline delayed gastric emptying. GA improved with low-dose ADTx; the precise mechanism of action is unknown warranting further study.
Background
Acetylcholinesterase inhibitors (ACIs), e.g., neostigmine, are known to increase upper and lower gastrointestinal (GI) motility and are used to treat acute colonic pseudoobstruction. ...However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity.
Methods
In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy.
Key Results
The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity (p < 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction.
Conclusions & Inferences
Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer‐acting ACIs for treating antroduodenal dysmotility warrant further study.
Intravenous neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction.
SUMMARY
While traditional geoelectric array configurations, such as the Wenner–Schlumberger or the dipole–dipole, can provide very good images of 1-D or robust 2-D structures, they are not ...sufficiently sensitive to those inhomogeneities that have a small effect on the surface electrical potential distribution. The detection and description of such inhomogeneities become possible by applying quasi-null arrays, which provide very small (close to zero) signals above a homogeneous half-space. The imaging properties of the members of an array series containing such arrays, the so-called γ11n arrays (n = 1–7), are demonstrated and compared to those of the most popular traditional arrays. Although the field applicability of the quasi-null arrays has been heavily questioned, it was demonstrated by our quasi-field analogue modelling experiments. The quasi-field tests also validated all of the numerical modelling results as follows: (1) many or all of the γ11n arrays were able to detect prisms and vertical sheets located at depths larger than those detectable by traditional geoelectric arrays, including the optimized Stummer configuration; (2) the horizontal resolution of the γ11n arrays proved to be better than the horizontal resolution of traditional arrays; (3) with n increasing, the γ11n arrays proved to be less sensitive to 1-D, but more sensitive to 2-D bodies. In case of high n values, the γ11n arrays may even be entirely insensitive to any 1-D structure. On the basis of the quasi-field experiments, γ11n arrays are expected to be very efficient to indicate bodies, or variations in time that only have a small impact on the surface electrical potential distribution (e.g. caves, mines, tunnels, tubes, cables, fractures, dykes), or small changes in the subsurface conditions (monitoring of dams or waste deposits). Data acquisition by both a traditional and a γ11n array, individual inversion of their data, and a joint interpretation of the results are recommended to obtain both a robust image and fine details of the subsurface.
Background
Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under‐recognized etiology. We ...evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID).
Methods
Twenty‐three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006–February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy–manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6–12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies).
Key Results
Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra‐intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re‐evaluated had scintigraphic evidence of improvement. The majority of responders who were re‐evaluated had improvement in autonomic testing (six of seven) or manometry (two of two).
Conclusions & Inferences
This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy.
In this article, we report 23 patients seen by members of this study group with suspected AGID in whom an immunotherapy trial (with intravenous immune globulin or methylprednisolone) was undertaken. The 17 responders described in this study provide the first objective evidence that immunotherapy may reverse autoimmune gastrointestinal dysmotility and illustrate the practical importance of considering an autoimmune basis for acquired idiopathic gastrointestinal motility disorders. Symptomatic improvements were generally accompanied by objective evidence of improved gastrointestinal motility and autonomic function on repeated scintigraphic, manometric, and autonomic function tests. These supportive tests offer useful surrogate markers of improvement for future randomized controlled clinical trials.
Background
Colonic pseudo‐obstruction (CPO) is characterized by colonic distention in the absence of mechanical obstruction or toxic megacolon. Concomitant secretory diarrhea (SD) with hypokalemia ...(SD‐CPO) due to gastrointestinal (GI) loss requires further characterization.
Aim
To perform a systematic review of SD‐CPO, report a case study, and compare SD‐CPO with classical CPO (C‐CPO).
Methods
We performed a search of MEDLINE, EMBASE, Cochrane, and Scopus for reports based on a priori criteria for CPO, SD and GI loss of potassium. An additional case at Mayo Clinic was included.
Results
Nine publications met inclusion criteria, with a total of 14 cases. Six studies had high, three moderate, and our case high methodological quality. Median age was 74 years (66‐97), with 2:1 male/female ratio. Kidney disease was present in 6/14 patients. Diarrhea was described as profuse, watery, or viscous in 10 patients. Median serum, stool, and urine potassium concentrations (mmol/L) were 2.4 (range: 1.9‐3.1), 137 (100‐180), and 17 (8‐40), respectively. Maximal diameter of colon and cecum (median) were 10.2 cm and 10.5 cm, respectively. Conservative therapy alone was effective in five out of 14 patients. Median potassium supplementation was 124 mEq/d (40‐300). Colonic decompression was effective in three out of six patients; one had a total colectomy; three out of 14 had died. The main differences between SD‐CPO and C‐CPO were lower responses to treatments: conservative measures (35.7% vs 73.6%, P=.01), neostigmine (17% vs 89.2%, P<.001), and colonic decompression (50% vs 82.4%, P=.02).
Conclusion
SD‐CPO is a rare phenotype associated with increased fecal potassium and is more difficult to treat than C‐CPO.
Colonic pseudo‐obstruction is not usually associated with secretory diarrhea and severe hypokalemia (SD‐CPO). Renal disease may be a predisposing factor for the development of SD‐CPO. Patients have worse response to conservative therapy, neostigmine, colonoscopic decompression, and cecotomy. Patients may have higher mortality than observed with classical CPO. A trial of colonic decompression with concomitant use of potassium‐sparing agents is warranted, with close monitoring of potassium levels. SD‐CPO phenotype requires a distinctive clinical approach in diagnosis and management.
Background
Nausea, vomiting, and constipation (OIC) are common adverse effects of acute or chronic opioid use. Naloxegol (25 mg) is an approved peripherally active mu‐opiate opioid receptor ...antagonist.
Aim
To compare the effects on pan‐gut transit of treatment with codeine, naloxegol, or combination in healthy volunteers.
Methods
We conducted a randomized, double‐blind, placebo‐controlled, single‐center, parallel‐group study in 72 healthy opioid‐naïve adults, randomized to: codeine (30 mg q.i.d.), naloxegol (25 mg daily), codeine and naloxegol, or matching placebo. During 3 days of treatment, we measured gastric emptying (GE) T1/2, colonic filling at 6 hours (CF6), colonic geometric center at 24 and 48 hours, and ascending colon emptying (ACE) T1/2.
Key Results
Participants were 59.7% women, median BMI 25.0 kg/m2, and median age 33.8 years. Codeine significantly retarded GE T1/2, CF6, overall colonic transit, and ACE T1/2. There was significant difference (P = .026) in GE T1/2 between codeine (144.0 min IQR 110.5‐238.6) and naloxegol (95.5 min 89.1‐135.4). There was a significant overall group difference in CF6 (P = .023), with significant difference (P = .019) between codeine (11.0% 0.0‐45.0) and naloxegol (51% 18.8‐76.2). However, no significant differences were found between codeine‐treated participants concomitantly receiving placebo or naloxegol.
Conclusions and Inferences
Short‐term administration of naloxegol (25 mg) in healthy, opioid‐naïve volunteers does not reverse the retardation of gastric, small bowel, or colonic transit induced by acute administration of codeine. Further studies with naloxegol at higher dose are warranted to assess the ability to reverse the retardation of transit caused by acute administration of codeine in opioid‐naïve subjects.
Nausea, vomiting, and constipation are common adverse effects of acute or chronic opioid use. We compared the effects on pan‐gut transit of treatment with codeine, naloxegol, or combination in healthy opioid‐naïve volunteers. Short‐term administration of naloxegol (25 mg) in healthy, opioid‐naïve volunteers does not reverse the retardation of gastric, small bowel or colonic transit induced by acute administration of codeine.
The Ciomadul is the youngest volcano of the Carpathian–Pannonian region, which erupted last time at 32ka. It produced high-K dacitic lava domes and pumiceous pyroclastic rocks. The dacite is ...crystal-rich and contains plagioclase, amphibole in addition to biotite, titanite, apatite, zircon and occasionally quartz, K-feldspar as well as olivine, clinopyroxene and orthopyroxene. There are two groups of amphiboles, characterized by low-Al and high-Al, respectively. They occur in the same samples and also as different zones of the same crystals. Thermobarometric calculations suggest that the low-Al amphiboles were formed from a low temperature (<800°C) silicic magma, whereas the high-Al amphiboles crystallized at about 950°C from a more mafic melt. A near-solidus silicic crystal mush body was stored at 7–14km depth, where an eruptible magma batch was produced by major reheating (about 200°C temperature increase) due to the intrusion of hot mafic magma into the silicic magma reservoir. A magnetotelluric survey was performed to reveal whether any melt-bearing magma body could presently reside beneath the volcano. Both the 2D and 3D inversion modeling calculations indicate low electric resistivity values in the depth interval of 5–25km, just beneath the volcanic centers. This can be interpreted as implying a partially melted zone, i.e. a crystal mush body containing about 5–15% melt fraction. In addition, the 2D modeling calculation indicates also a deeper low resistivity anomaly at 30–40km depth. The consistent petrologic and magnetotelluric constrains on the magma storage beneath Ciomadul are corroborated by the recent seismic tomography result, which pointed out a low-velocity anomaly at 8–20km depth zone. Thus, results of independent models suggest the presence of a melt-bearing crystal mush body beneath the seemingly inactive volcano. Since there are implications for long repose periods during the lifetime of the volcano as well as for effective and rapid remobilization of the low-temperature silicic crystal mush body prior to volcanic eruptions, the present existence of a low melt fraction silicic crystal mush beneath Ciomadul could mean that there is still a potential for a rejuvenation in the future. We suggest for long-dormant or seemingly inactive volcanoes, such as Ciomadul, having melt-bearing magmatic body at depths to term as ‘volcano with potentially active magma storage’ or PAMS volcano.
•Combined use of petrologic and magnetotelluric data to constrain the magma storage•The amphibole barometry indicates that the magma chamber could have been at 8–13km depth.•The long lasting crystal mush was reheated by intruding basaltic magmas prior to the volcanic eruptions.•The magnetotelluric data imply a mushy magmatic body with 5–15% melt fraction beneath the Ciomadul.•Suggestion a term as ‘volcano with potentially active magma storage’ or PAMS volcano
Background Despite the relatively high prevelance of gastroparesis and functional dyspepsia, the aetiology and pathophysiology of these disorders remain incompletely understood. Similarly, the ...diagnostic and treatment options for these two disorders are relatively limited despite recent advances in our understanding of both disorders.
Purpose This manuscript reviews the advances in the understanding of the epidemiology, pathophysiology, diagnosis, and treatment of gastroparesis and functional dyspepsia as discussed at a recent conference sponsored by the American Gastroenterological Association (AGA) and the American Neurogastroenterology and Motility Society (ANMS). Particular focus is placed on discussing unmet needs and areas for future research.
PDF
