Emmanuel Papillon

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.

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.