Gervais Tougas

Gastric electrical stimulation for medically refractory gastroparesis

BACKGROUND & AIMSnThis study investigated the efficacy of gastric electrical stimulation for the treatment of symptomatic gastroparesis unresponsive to standard medical therapy.nnnMETHODSnThirty-three patients with chronic gastroparesis (17 diabetic and 16 idiopathic) received continuous high-frequency/low-energy gastric electrical stimulation via electrodes in the muscle wall of the antrum connected to a neurostimulator in an abdominal wall pocket. After implantation, patients were randomized in a double-blind crossover design to stimulation ON or OFF for 1-month periods. The blind was then broken, and all patients were programmed to stimulation ON and evaluated at 6 and 12 months. Outcome measures were vomiting frequency, preference for ON or OFF, upper gastrointestinal tract symptoms, quality of life, gastric emptying, and adverse events.nnnRESULTSnIn the double-blind portion of the study, self-reported vomiting frequency was significantly reduced in the ON vs. OFF period (P < 0.05) and this symptomatic improvement was consistent with the significant patient preference (P < 0.05) for the ON vs. OFF period determined before breaking the blind. In the unblinded portion of the study, vomiting frequency decreased significantly (P < 0.05) at 6 and 12 months. Scores for symptom severity and quality of life significantly improved (P < 0.05) at 6 and 12 months, whereas gastric emptying was only modestly accelerated. Five patients had their gastric electrical stimulation system explanted or revised because of infection or other complications.nnnCONCLUSIONSnHigh-frequency/low-energy gastric electrical stimulation significantly decreased vomiting frequency and gastrointestinal symptoms and improved quality of life in patients with severe gastroparesis.

Assessment of gastric emptying using a low fat meal: establishment of international control values.

OBJECTIVE:The diagnosis of gastroparesis implies delayed gastric emptying. The diagnostic gold standard is scintigraphy, but techniques and measured endpoints vary widely among institutions. In this study, a simplified scintigraphic measurement of gastric emptying was compared to conventional gastric scintigraphic techniques and normal gastric emptying values defined in healthy subjects.METHODS:In 123 volunteers (aged 19–73 yr, 60 women and 63 men) from 11 centers, scintigraphy was used to assess gastric emptying of a 99Tc-labeled low fat meal (egg substitute) and percent intragastric residual contents 60, 120, and 240 min after completion of the meal. In 42 subjects, additional measurements were taken every 10 min for 1 h. In 20 subjects, gastric emptying of a 99Tc-labeled liver meal was compared with that of the 99Tc-labeled low fat meal.RESULTS:Median values (95th percentile) for percent gastric retention at 60, 120, and 240 min were 69% (90%), 24% (60%) and 1.2% (10%) respectively. A power exponential model yielded similar emptying curves and estimated T50 when using images only taken at 1, 2 and 4 h, or with imaging taken every 10 min. Gastric emptying was initially more rapid in men but was comparable in men and women at 4 h; it was faster in older subjects (p < 0.05) but was independent of body mass index.CONCLUSIONS:This multicenter study provides gastric emptying values in healthy subjects based on data obtained using a large sample size and consistent meal and methodology. Gastric retention of >10% at 4 h is indicative of delayed emptying, a value comparable to those provided by more intensive scanning approaches. Gastric emptying of a low fat meal is initially faster in men but is comparable in women at 4 h; it is also faster in older individuals but is independent of body mass.

Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: findings from the DIGEST study

Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: findings from the DIGEST study

Upper Gastrointestinal Symptoms in North America

The aim of this study was to determine the prevalence of upper gastrointestinal symptoms (UGIS) in a general population and quantify the relationship of those symptoms to health-care utilization and quality of life. In-person interviews were conducted with 2056 United States and Canadian residents selected at random. Subjects reported frequency and severity for 11 symptoms, prescription and over-the-counter medication use, primary care and specialty physician visits in prior three months, and completed the Psychological General Well-Being Scale. For analyses, subjects were classified into four mutually exclusive symptom groups: gastroesophageal reflux disease (GERD) -like, GERD plus motility-like (GERD+), ulcerlike, and motility-like. Of the total sample, 51.4% reported the occurrence of at least one UGIS in the prior three months. Subjects in the GERD+ and ulcer groups used more prescription medications and were more likely to see a physician about the symptoms (P < 0.001). Subjects with symptoms demonstrated poorer quality of life compared to subjects with no symptoms. The prevalence of UGIS in the general population is high and symptoms are associated with significant health-care utilization and poorer quality of life.

Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: findings from the DIGEST study. Domestic/International Gastroenterology Surveillance Study.

Objective:The prevalence and impact of upper gastrointestinal (GI) symptoms in the general population are poorly defined. Most data are obtained from selected samples derived from patients presenting to health care providers. As part of a larger international effort (The DIGEST study), we examined the prevalence of upper GI symptoms among the general Canadian population, as well as their psychosocial and economic impact.Methods:A sample of 1036 adults was studied, its demographic characteristics closely matching those of the general Canadian population. A validated detailed questionnaire measured the prevalence, severity, and frequency of 15 digestive symptoms, as well as demographic information, use of medication and medical resources, other illnesses, and dietary habits. The Psychological General Well-Being Index, a self-administered questionnaire, assessed the individuals subjective sense of well-being.Results:Of the sample population, 28.6% reported substantial symptoms in the preceding 3 months, the majority (111/153 subjects) for >1 yr; 34.1% reported having never experienced significant GI symptoms.The most bothersome symptoms were primarily related to dysmotility-like symptoms in 54.9% of those with chronic symptoms, ulcer-like symptoms in 12.4%, and related to heartburn in 42.5%. Chronic upper GI symptoms were associated with a highly significant (p < 0.001) decrease in all facets of the Psychological General Well Being Index.Conclusion:Upper GI symptoms are very prevalent in the general Canadian population and substantially affect the quality-of-life and psychological well-being of those affected. Dysmotility-like symptoms, rather than heartburn, are the most common chronic upper gastrointestinal symptoms in the general population.

Standardization of a simplified scintigraphic methodology for the assessment of gastric emptying in a multicenter setting

OBJECTIVE:Scintigraphy remains the gold standard to study gastric emptying. The technique is onerous and normal values vary between centers. Standardized protocols, although desirable, are not presently available. We validated a simplified scintigraphic protocol in a multicenter setting.METHODS:In 69 healthy volunteers from seven Canadian institutions, gastric emptying of a standard meal (99mTc- labeled beef liver) was assessed by scintigraphy every 10 min for 1 h, then every 20 min for the next 2 h. Gastric retention was fitted to a power exponential model, Propt={−(κt)β} with Propt= proportion of retention at time t, either using all 13 time intervals (conventional technique) or using measurements at 0, 1, 2, and 3 h (simplified technique).RESULTS:The power exponential model yielded identical emptying curves and T ½ values with both techniques. Gastric emptying was more rapid in men than in women < 35 yr (p < 0.01) and in younger than in older men (p < 0.005). Gastric emptying was slower in women from Québec than in women from Ontario (p < 0.04). Gastric retention was similar at 1, 2, and 3 h among the seven centers. Gastric emptying of a beef liver meal was slower than that of a low fat egg substitute (p < 0.03).CONCLUSIONS:A simpler scintigraphic approach, using four rather than 13 samples, provides results comparable to those of the conventional technique. This simpler approach provides an economical, yet accurate, alternative to the techniques presently used and is applicable to a multicenter setting.

Abnormal cerebral processing of oesophageal stimuli in patients with noncardiac chest pain (NCCP).

In noncardiac chest pain (NCCP), altered visceral perception may result from abnormal cerebral processing of sensory input rather than abnormalities of afferent pathways. However, the interactions between symptoms, autonomic function and oesophageal stimuli are poorly studied. Oesophageal stimulation elicits reproducible cortical evoked potentials [CEP] and modulates heart rate variability via vagal pathways, as visible on power spectrum analysis of heart rate variability [PS‐HRV]. These methods are increasingly used to study the function of visceral afferent neural pathways in human. The aim of this study was to compare EP and PS‐HRV during oesophageal stimuli in NCCP and controls. Twelve healthy volunteers (one female, 11 male; aged 24–51u2003years; mean 32u2003±u20038 years), and eight NCCP patients (three female, five male; age range 26–58, mean 40.5u2003±u200310u2003years) were studied. Electrical oesophageal stimulation (EOS; 200u2003μs, 0.2u2003Hz, 25 stimuli) was applied to the oesophageal wall 5u2003cm above the lower oesophageal sphincter (LOS), and perception thresholds (measured in mA) determined. EP responses were recorded using 22 standard electroencephalogram scalp electrodes. Autonomic activity was assessed using PS‐HRV, before, during, and after oesophageal stimulation. Measured PS‐HRV indices included high frequency (HF; 0.15–0.5u2003Hz) and low frequency (LF; 0.06–0.15u2003Hz) power, respectively, assessing vagal and sympathetic activity, and the LF/HF ratio. EOS perception occurred at lower thresholds in NCCP than in controls (3.6u2003±u20031 vs. 7.8u2003±u20032 mA, Pu2003<u20030.05). EP amplitude was greater (13u2003±u20032 vs. 6u2003±u20031u2003μV, Pu2003<u20030.0001), and latency longer in controls vs. NCCP (191u2003±u20037u2003ms vs. 219u2003±u20036u2003ms, Pu2003<u20030.001). In NCCP, EOS decreased sympathetic outflow (low frequency peak on PS‐HRV) and increased cardiovagal activity (high frequency peak, Pu2003<u20030.02) to a significantly higher degree in comparison with controls. During EOS, heart rate decreased in NCCP from 68 vs. 62 beatsu2003min–1 (Pu2003<u20030.003) but not in controls. In NCCP patients, EOS was perceived at lower intensities and was associated with a greater cardiovagal reflex response. EP responses associated with EOS were smaller in NCCP than in controls, suggesting that an increased perception of oesophageal stimuli results from an enhanced cerebral processing of visceral sensory input in NCCP, rather than from hyperalgesic responses in visceral afferent pathways.

Long-term efficacy of Botulinum toxin in classical achalasia: a prospective study

OBJECTIVE:We sought to examine the long-term efficacy of intrasphincteric Botulinum toxin A injection in a prospective cohort study of 30 patients with achalasia.METHODS:Thirty patients with classical achalasia were treated with intrasphincteric Botulinum toxin A injection. Follow-up consisted of clinical assessment, symptom scoring, and postinjection manometry.RESULTS:Symptomatic improvement for >3 months was seen in 23 of 30 patients (77%). Of the 23 initial responders, seven (30%) experienced a sustained symptomatic response after a single Botulinum toxin injection (mean follow-up, 21 months). The remaining 16 initial responders (70%) eventually relapsed (mean initial response, 11 months). Nine received a 2nd Botulinum toxin injection, and seven experienced an ongoing response (mean duration, 9 months); two patients eventually required a 3rd injection with good effect (mean duration, 22 months). The remaining seven patients who relapsed after Botulinum toxin opted for pneumatic dilation or surgical myotomy. Five of the seven patients who had no initial response received a 2nd injection but again did not respond. A residual lower esophageal sphincter pressure <18 mm Hg after the first Botulinum toxin injection predicted a good response to Botulinum therapy (single or multiple injections, p < 0.002, positive predictive value = 0.71, negative predictive value = 1.0). Neither initial nor sustained response to Botulinum toxin could be predicted based on gender, age, duration of illness, previous pneumatic dilation, or esophageal motility before treatment.CONCLUSIONS:We found that 77% of patients with classical achalasia experienced a good symptomatic response after Botulinum toxin and 30% of initial responders achieve sustained symptomatic relief after a single treatment with Botulinum toxin. The initial responders who relapsed did well with subsequent Botulinum toxin A. Lack of an initial symptomatic response and residual lower esophageal sphincter pressure ≥18 mm Hg after Botulinum toxin are associated with a poor response.

Integration of vagal afferent responses to duodenal loads and exogenous CCK in rats

The neurophysiological responses to 0.1 ml duodenal balloon inflation, 0.5 ml duodenal loads of normal saline, and 100 pmol close celiac arterial infusions of cholecystokinin (CCK) were obtained from 14 left cervical vagal afferent fibers in 14 rats. Duodenal, but not gastric, loads increased discharge rates in these slowly adapting fibers. CCK alone excited these fibers, and CCK pretreatment amplified subsequent duodenal load responses. Furthermore, duodenal loads generated greater responses when combined with CCK infusions. The small (< 3 mm) receptive fields of these fibers were localized to the ventral wall of the proximal duodenum, with C fiber conduction velocities (< 2 m/s). These results demonstrate for the first time rat duodenal load-sensitive vagal afferents. They can integrate signals arising from CCK and duodenal loads, and may mediate aspects of the role of CCK in the inhibition of gastric emptying and the control of food intake.

The Autonomic Nervous System in Functional Bowel Disorders

Communications along the brain-gut axis involve neural pathways as well as immune and endocrine mechanisms. The two branches of the autonomic nervous system are integrated anatomically and functionally with visceral sensory pathways, and are responsible for the homeostatic regulation of gut function. The autonomic nervous system is also a major mediator of the visceral response to central influences such as psychological stress. As defined, functional disorders comprise a constellation of symptoms, some of which suggest the presence of altered perception, while other symptoms point to disordered gastrointestinal function as the cause of the symptoms. A growing number of reports have demonstrated disordered autonomic function in subgroups of functional bowel patients. While a number of different methods were used to assess autonomic function, the reports point to a generally decreased vagal (parasympathetic) outflow or increased sympathetic activity in conditions usually associated with slow or decreased gastrointestinal motility, while other studies found either an increased cholinergic activity or a decreased sympathetic activity in patients with symptoms compatible with an increased motor activity. Under certain conditions, altered autonomic balance (including low vagal tone and increased sympathetic activity) may alter visceral perception. Autonomic dysfunction may also represent the physiological pathway accounting for many of the extraintestinal symptoms seen in irritable bowel syndrome patients and some of the frequent gastrointestinal complaints reported by patients with disorders such as chronic fatigue and fibromyalgia.