Jacques Fournet

Central processing of rectal pain in patients with irritable bowel syndrome: an fMRI study

OBJECTIVES:In healthy subjects, the neural correlates of visceral pain bear much similarity with the correlates of somatic pain. In patients with irritable bowel syndrome, the central nervous system is believed to play a strong modulatory or etiological role in the pathophysiology of the disease. We hypothesize that this role must be reflected in aberrations of central functional responses to noxious visceral stimulation in these patients. To verify this hypothesis, we have induced transient rectal pain in patients and assessed the functional responses of the brain by means of functional magnetic resonance imaging.METHODS:Twelve right-handed patients (11 female) were examined. Functional imaging (1.5 T) was performed following a block paradigm, alternating epochs with and without noxious stimulation of the rectum. Rectal pain was induced by inflating a latex balloon. Whole-brain coverage was achieved by means of echo-planar magnetic resonance acquisition.RESULTS:A strong variability of the individual responses to rectal pain was found in patients with irritable bowel syndrome. Significant activations were found in only two patients, and group analysis did not reveal significant activations. In contrast, all patients exhibited significant deactivations. Group analysis revealed significant deactivations within the right insula, the right amygdala, and the right striatum.CONCLUSIONS:This study reveals aberrant functional responses to noxious rectal stimulation in patients with irritable bowel syndrome. Those results add grounds to the hypothesis that the central nervous system plays a significant role in the pathophysiology of this syndrome.

Effective use of argon plasma coagulation in the treatment of severe radiation proctitis

PURPOSE: Chronic radiation proctitis, a well described complication of pelvic radiation therapy, can result in severe bleeding that is refractory to conventional treatment. Argon plasma coagulation is an effective treatment for hemorrhagic lesions of the gastrointestinal tract. The aim of this study was to assess the efficacy and safety of argon plasma coagulation in the management of severe radiation proctitis resistant to medical treatment. METHODS: Eleven patients (10 males) aged between 54 and 86 years (mean ± standard error of the mean, 73±3.years), with chronic radiation proctitis after radiotherapy for prostate (n=9), uterine (n=1) or rectal (n=1) cancer were enrolled in this prospective study. Traditional therapies had failed including mainly topical steroids, 5-aminosalicylic acid and sometimes sucralfate. All patients had active bleeding from diffuse telangiectasias responsible for chronic anemia and seven of them required blood transfusions. The mean duration of the sessions was 20 minutes and one to five sessions (mean, 3.2±0.4), usually without anesthesia, were required to stop bleeding. Mean follow-up time was 19±2 (range, 7–30) months. RESULTS: Rectal bleeding disappeared in nine patients and was greatly reduced in two. All the patients were free of transfusions during the mean follow-up of 19 months. The mean hemoglobin level was 7.7±2.8 g/dl at the first session and increased significantly (P=0.003) to 11.5±2.6 g/dl after treatment. In two patients, a rectal stenosis appeared 7 and 11 months after the first session. CONCLUSION: Argon plasma coagulation is a simple, inexpensive and effective treatment for severe refractory radiation proctitis with telangiectasias. Follow-up supervision is in progress to evaluate long term benefits and the risk of rectal stenosis.

Chronic intestinal pseudoobstruction with myopathy and ophthalmoplegia. A muscular biochemical study of a mitochondrial disorder.

SummaryThe association of chronic intestinal pseudoobstruction with ophthalmoplegia has been reported previously in visceral myopathies. We report a case of this association in which muscle mitochondria had a crystalline appearance, a dense core, and decreased cytochromec oxidase and succinate cytochromec reductase activities. The absence of evident mitochondrial DNA deletion in the skeletal muscle of this patient does not exclude the possibility of localized deletion or mutation of mitochondrial DNA in digestive muscle.

Increased urinary F2-isoprostanes in patients with Crohn’s disease

OBJECTIVE:Reactive oxygen metabolites have been suggested to participate in the pathogenesis of Crohns disease, but the evidence supporting this contention in vivo is incomplete. Isoprostaglandin F2α type III (iPF2α-III, or 15-F2t-IsoP) is a prostaglandin F2α isomer produced in vivo by free radical-catalyzed peroxidation of arachidonic acid. We aimed to investigate urinary iPF2α-III concentrations as an index of lipid peroxidation in 23 patients with Crohns disease compared with 23 healthy controls, and to test whether lipid peroxidation correlates to clinical relapse and inflammation.METHODS:Urinary iPF2α-III was measured by gas chromatography/electronic impact mass spectrometry.RESULTS:Urinary iPF2α-III concentrations were significantly higher in patients with Crohns disease than in healthy controls (median [range] = 130 [38–622] vs 91 [35–152] pmol/mmol of creatinine, respectively; p < 0.01). There was a trend toward significance for patients with clinical relapse versus patients with clinical remission (median [range] = 155 [38–622] vs 96 [64–253] pmol/mmol of creatinine, respectively; p = 0.09). A significant correlation was found between urinary iPF2α-III and plasma C-reactive protein concentrations, suggesting a link between lipid peroxidation and inflammation.CONCLUSION:This study provides evidence of increased lipid peroxidation in patients suffering from Crohns disease, especially in patients with clinical relapse. iPF2α-III quantification has to be investigated as a prognosis biomarker in patients suffering from Crohns disease.

Relationship between acid reflux episodes and gastroesophageal reflux symptoms is very inconstant.

In this prospective study 244 consecutive patients presenting with typical and chronic signs of gastroesophageal reflux were included. Conventional 24-hr esophageal pH monitoring was carried out to establish the symptom association probability, the concordance index, and the symptom sensitivity index. The symptom association probability could be calculated in 110 patients (45%). Two groups were identified: group 1 had normal duration of esophageal acid exposure; subgroup 1a (nonsignificant symptom association probability) included 39 patients (35.5%) and subgroup 1b (significant symptom association probability) included 24 patients (21.8%); group 2 had abnormal duration of esophageal acid exposure; subgroup 2a (nonsignificant symptom association probability) included 21 patients (19.1%) and subgroup 2b (significant symptom association probability) included 26 patients (23.6%). In all, 56.6% of the patients presented typical symptoms of reflux not directly determined by one or repeated acid reflux episodes. The correlation between symptom association probability and the symptom sensitivity index allows for more accurate determination of esophageal acid sensitivity (subgroups 1b and 2b).

A malignant gastrointestinal stromal tumour in a patient with multiple endocrine neoplasia type 1

Loss of heterozygosity for polymorphic markers flanking the multiple endocrine neoplasia type 1 (MEN-1) gene in parathyroid and pancreatic islet tumours from subjects with MEN-1 has been well documented and has led to the hypothesis that the MEN-1 gene functions as a recessive tumour suppressor gene. We report a case of MEN-1 with duodeno-pancreatic gastrinoma, parathyroid hyperplasia, pituitary adenoma, adrenal adenoma, and lipomas, whose rare association with a malignant gastrointestinal stromal tumour (GIST) represents an undescribed combination. MEN-1 mutation in this family was shown as a frameshift (1607delA) in exon 10. To assess the role of the MEN-1 gene in the pathogenesis of tumours less commonly associated with MEN-1, we studied GIST DNA for loss of the unaffected MEN-1 gene allele. Stromal tumour and peripheral leucocyte DNAs from our patient were examined for loss of heterozygosity using the PYGM microsatellite polymorphism and an intragenic polymorphism (D418D in exon 9) in the MEN-1 gene. We showed no evidence for loss of the wild-type MEN-1 allele in GIST. The MEN-1 germline inactivating mutation 1607delA-ter558 in exon 10 was detected in the stromal tumour DNA, but no somatic mutation in the wild-type MEN-1 allele in GIST DNA was detected. Occurrence of GIST could be consistent with the possibility that this MEN-1-related uncommon neoplasm arose independently by a mechanism unrelated to the MEN-1 gene.

Oesophageal motor and sensitivity abnormalities in non-obstructive dysphagia.

Objectives To evaluate oesophageal sensitivity to balloon distension in patients with non-obstructive dysphagia (NOD), and to determine its relationship with the motility pattern in response to food ingestion. Patients and methods Twenty-one healthy volunteers and 19 consecutive patients complaining of NOD with normal standard manometry were included. An oesophageal sensitivity test was carried out before the manometry study with liquid and solid swallows. Results The median threshold to distension was 9 ml in control subjects and 5 ml in patients (P < 0.002). Dysphagia or odynophagia were reproduced in 15/19 (78.9%) patients during manometry with solid swallows only. The percentage of swallows with abnormal motility patterns was higher in patients than control subjects (P < 0.001). Compared with control values, sensitivity abnormality was defined by a distension threshold of < 6 ml. Motor abnormality was defined by > 19% of swallows occurring with one or more abnormal motor profiles. A total of 8/19 (42%) patients presented with the association of an abnormal sensitivity threshold and an abnormal motor pattern; 5/19 (26%) presented with isolated motor abnormalities; 4/19 (21%) patients presented with isolated abnormal sensitivity thresholds; and 2/19 (11%) patients presented without any abnormality. Conclusion Manometry with solid swallows and oesophageal balloon distension are useful in characterizing NOD.

Is there an abnormal fasting duodenogastric reflux in nonulcer dyspepsia

A quantitatively and/or qualitatively abnormal duodenogastric reflux (DGR) could be involved in the pathogenesis of nonulcer dyspepsia (NUD). The aims of this prospective study were to look for (1) a pathological DGR profile during fasting and (2) an eventual correlation between DGR profile and clinical symptoms. Twenty-six NUD patients were investigated. Seven other operated patients with a surgical procedure facilitating DGR episodes and 27 healthy volunteers served as control groups. A clinical score was determined for each patient from a standardized questionnaire. Gastric aspiration was performed for 6 hr in fasting subjects. The aspirates were pooled into 17 samples. In each sample the concentration and the output of total bile acids was determined. If the concentration was larger than 30 μmol/liter in pooled samples, the concentrations of free bile acids and the distribution of the conjugated bile acids was determined. The percentage of aliquots with a total bile acid concentration larger than 50 μmol/liter (without upper limit), and the percentage with a concentration larger than 2500 μmol/liter was also obtained. No significant difference was demonstrated between the healthy volunteers and NUD patients, whatever the parameter considered. However, there was a significant increase in each of the quantitative parameters for the group of operated patients in comparison with the NUD patient group. No significant correlation was found between the clinical score and the DGR profile in NUD patients. Apparently, DGR episodes do not play a primary role in the pathogenesis of NUD.

Role of upper esophageal reflex and belch reflex dysfunctions in noncardiac chest pain

Fifty-four patients examined for noncardiac chest pain (NCCP), showing no esophageal motor disorder or gastroesophageal reflux disease compatible with NCCP, were subjected to an intraesophageal balloon distension test and a study of the belching reflex provoked by intraesophageal air injection. Thirty-three control subjects were also studied, allowing us to define high-threshold belchers (group I) as those who belched during two of three 40-ml distensions and low-threshold belchers (group II) as those who did not. The balloon distension test induced NCCP in 64% of the patients in group I, and in 14% of the patients in group II (P<0.01). High-threshold belching was a factor favoring the positivity of the balloon distension test. This result supports the hypothesis that esophageal distension by air due to a belching disorder may be the mechanism responsible for NCCP in some patients with an abnormal sensitivity to balloon distension.

Scintigraphic study of gallbladder emptying and duodenogastric reflux during non-ulcerous dyspepsia

Cholescintigraphy with technetium 99m hydroxy imino diacetic acid (99mTc-HIDA) was used to study gallbladder emptying (GE) and duodenogastric reflux (DGR) simultaneously during the postprandial period in humans. Two groups of subjects were examined prospectively; one was a group of healthy volunteers (n = 14) and the other a group of patients with nonulcerous dyspepsia (NUD) (n = 22). Symptoms were quantified using a clinical score (CS). GE kinetics was quantified according to two indices. DGR episodes were detected by an image-subtraction method and quantified. The group of patients with NUD showed significant early acceleration of GE (P > 0.01). One DGR episode equivalent to 1% of the injected dose was observed in 1 of the 14 control subjects, and >1% in 3 of the 22 NUD patients. However, there was no correlation between the CS, GE kinetics and DGR episodes. The physiopathological mechanism and clinical significance of these digestive motility anomalies remain to be demonstrated.