Lars Torsten Larsson

Widespread changes in neurotransmitter expression and number of enteric neurons and interstitial cells of Cajal in lethal spotted mice: an explanation for persisting dysmotility after operation for Hirschsprung's disease?

Gastrointestinal motor dysfunction persists in a large number of children subjected to surgical treatment for Hirschsprungs disease, indicating abnormalities in the remaining intestine. The aim of the study was to detect possible alterations in frequency and topographic distribution of enteric neurons and interstitial cells of Cajal in an experimental model (the lethal spotted mouse displaying a short rectal aganglionosis) for Hirschsprungs disease. Specimens from the intestinal tract from homozygous (aganglionic) and heterozygous (healthy littermates) were examined using histochemistry, in situ hybridization, and immunohistochemistry. In ileum and colon, ie, regions proximal to the aganglionosis, changes in the expression of neuropeptides and neuronal nitric oxide synthase and in the number of enteric neurons and interstitial cells of Cajal could be detected in homozygous versus heterozygous mice. The described changes are suggested to contribute to the dysmotility remaining after surgical resection of the aganglionic segment in Hirschsprungs disease.

Sacrococcygeal teratoma in Sweden between 1978 and 1989: Long-term functional results☆

Thirty-four patients operated with sacrococcygeal teratoma in Sweden between 1978 and 1989 were reviewed. Twenty-five children were available for functional follow-up. The patients and their parents were interviewed for bowel and micturition habits. Fourteen patients from this number were subjected to anorectal manometry (56%). Fifteen children reported normal bowel habits (60%). In 10 patients (40%) soiling was observed. However, four of them were under 3 years of age and wearing diapers, which made the functional evaluation difficult. The manometries showed normal and resting tone and squeezing pressures in 10 patients and subnormal values in four patients who also had soiling problems. All investigated children showed normal rectoanal inhibition reflex. Twenty-one patients reported normal micturition, in four (16%) urinary incontinence was recorded. Two of the latter children required intermittent clean catheterization, one was on medication and the last one lives without any treatment. No difference in functional outcome was noted between patients with intrapelvic or extrapelvic tumor location. Retrospectively, it is not possible to know whether the observed functional outcome is due to tumor growth or the result of surgery. Preoperative clinical investigation and in some cases anorectal manometry and cystometry could theoretically resolve this problem.

A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: evidence for reduced content in Hirschsprung's disease

SummaryA novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), exhibits sequence homology with vasoactive intestinal polypeptide (VIP) and occurs in the mammalian brain, lung and gut. The distribution of PACAP in ganglionic and aganglionic portions of the large intestine of patients with Hirschsprungs disease was examined by immunohistochemistry and radioimmunoassay. PACAP-immunoreactive nerve fibers were distributed in all layers of the ganglionic and aganglionic segments of the intestine, although they were less numerous in the latter, and PACAP-immunoreactive nerve cell bodies were seen in the ganglionic portion of the intestine. The concentration of immunoreactive PACAP was lower in the aganglionic than in the ganglionic segment of the intestinal wall. PACAP and VIP were found to coexist in both ganglionic and aganglionic segments of the intestine. Apparently, PACAP participates in the regulation of gut motility. The scarcer PACAP innervation of the aganglionic segment may contribute to the defect in intestinal relaxation seen in patients with Hirschsprungs disease.

Complications of laparoscopy-aided gastrostomies in pediatric practice

PURPOSE The aim of this report is to establish the frequency and type of complications of laparoscopy-aided gastrostomy in pediatric practice and to identify patients at risk for postoperative complications. METHOD This is a follow-up study of 98 children with nutritional problems including inability to swallow, inadequate calorie intake in neurologically impaired children, patients with cystic fibrosis, malignancies, neurometabolic diseases, and cardiac malformations. Laparoscopy-aided gastrostomy was attempted in all patients. These patients have undergone follow-up at our outpatient clinic. Postoperative complications and problems with the gastrostomy device were registered. The postoperative complications were divided into minor problems and major or life-threatening complications. RESULTS There was no perioperative mortality. No life-threatening complication developed, whereas minor problems were common, necessitating medical attention postoperatively. Patients with congenital heart disease, chronic respiratory failure, and metabolic diseases experienced the highest frequency of postoperative complications. CONCLUSIONS The surgical placement of an enteral access device in children should be considered a major surgical procedure, demanding medical attention for 1 to 2 months postoperatively. The rate and severity of complications with the method described are tolerable considering the severity of the underlying diseases.

Lack of neuronal nitric oxide synthase in nerve fibers of aganglionic intestine : a clue to Hirschsprung's disease

The lack of nonadrenergic, noncholinergic (NANC) inhibitory innervation in aganglionic intestine is typical of Hirschsprungs disease. Several neuropeptides participating in the intestinal NANC innervation are greatly reduced in aganglionic intestine. However, these findings do not fully explain the pathophysiology of the disease. Recently, nitric oxide (NO) has been presented as a potent smooth muscle relaxant, and the enzyme responsible for its formation, nitric oxide synthase (NOS) has been demonstrated in neuronal elements in both the central and peripheral nervous system. In our study, nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining, a marker for NOS, and NOS immunohistochemistry revealed a dense innervation of the smooth muscle layers and the myenteric ganglia in ganglionic non afflicted intestine from patients with Hirschsprungs disease. By contrast, there was an almost complete lack of NOS-immunoreactive and NADPH-diaphorase-positive nerve fibers in the afflicted aganglionic bowel. NOS and vasoactive intestinal peptide were found to be partially colocalized in nerve fibers and neuronal cell bodies in the ganglionic but not in the aganglionic intestine. The lack of NO-producing nerve fibers in the aganglionic intestine probably contributes to the inability of the smooth muscle to relax, thereby causing lack of peristalsis in Hirschsprungs disease.

Neuropeptide Y, calcitonin gene-related peptide, and galanin in Hirschsprung's disease: an immunocytochemical study

The aganglionic intestinal segment in Hirschsprungs disease is known to contain a reduced number of nerve fibers storing vasoactive intestinal peptide (VIP), substance P (SP), enkephalin, and gastrin-releasing peptide (GRP). In this study, nerves containing three newly described neuropeptides: neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and galanin were examined using immunocytochemistry. Nerve fibers displaying NPY immunoreactivity were found to be more frequent in the aganglionic than in nonafflicted ganglionic intestine. Nerve fibers storing CGRP and galanin on the other hand were roughly equally frequent but the distribution pattern differed in that the bulk of fibers in the aganglionic intestine was localized to large nerve trunks not seen in the ganglionic segment. The functional significance of these changes has yet to be defined.

Quality of Life in Adults Operated On for Hirschsprung Disease in Childhood.

Objectives: The aim of this study is to explore the long-term quality of life (QoL) in adults after surgery for Hirschsprung disease in childhood. Patients and Methods: Altogether 51 patients were operated for HD at our center during the period 1969 to 1989. In 2007, the validated instruments for assessing QoL, the SF-36 health survey and the Gastrointestinal Quality of Life Index (GIQLI), were sent to the 47 patients still alive at the time of the study. A retrospective review of the patient records was also done. Results: Forty-two patients returned both questionnaires (89% response rate) at the median age of 28.5 (range 18–45) years. The median clinical follow-up time was 5.7 years (range 5 months–23 years). At the last clinical control, 4 (9%) patients had a terminal enterostomy, 12 (29%) had soiling, 5 (12%) had constipation, and 2 (5%) experienced recurrent enterocolitis. In contrast to males, the subscores for females were lower for general health and mental health than for an age- and sex-matched general population (P < 0.05). Patients having aganglionosis to the right colon had lower GIQLI scores than those with aganglionosis to the left colon (P < 0.05). In multivariate linear regression analysis, female sex was the only factor associated with lower GIQLI score (P < 0.05). Conclusions: The long-term QoL of adults operated for Hirschsprung disease in their youth is satisfactory. Female scores were lower for general and mental health, compared with the matched control group. The study indicates that the longer the aganglionic segment, the greater its impact on QoL in later life.

Ontogeny of peptide-containing neurones in human gut—an immunocytochemical study

Neurons containing enkephalin, substance P (SP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), galanin, calcitonin gene-related peptide (CGRP), peptide histidine isoleucine (PHI) or gastrin-releasing peptide (GRP) are known to occur in the human intestinal tract. The knowledge of the ontogeny of these neurones is, however, limited. Intestinal specimens from 24 human foetuses with gestational ages varying between 8 and 40 weeks were examined by immunocytochemistry. No peptide-containing neurones could be detected before the 14th week of gestation after which a rapid development was seen. Generally, peptide immunoreactivity was first noted in the myenteric ganglia and somewhat later in the other layers of the intestinal wall. There was no major difference between the peptides studied or between different parts of the intestinal tract with respect to time of appearance.

No increase in gastroesophageal reflux after laparoscopic gastrostomy in children.

The objective of the study was to assess the influence of a laparoscopic video-assisted gastrostomy on acid gastroesophageal reflux (GER). A prospective uncontrolled study included 23 neurologically disabled children, from 10 months to 15 years of age, all with severe nutritional problems and in need of a gastrostomy. They all had a history of clinical GER problems including vomiting, choking and chest infections. A 24-h pH monitoring was used for a quantitative assessment of GER the day before surgery and 12±3 months (7–22 months) postoperatively. The gastrostomy was placed on the anterior wall of the stomach near the lesser curvature. The main outcome measure was the comparison of the pre- and postoperative 24-h pH monitoring and the reflux index (RI), i.e. the percentage of time with pH below 4. The results showed a non-significant reduction of RI from 6.8±4.5 preoperatively to 3.7±2.0 postoperatively. We conclude that a gastrostomy using the video-assisted technique and placing the stoma on the anterior wall of the stomach close to the lesser curvature does not cause aggravation of acid reflux.

Hirschsprung's disease: A comparison of the nervous control of ganglionic and aganglionic smooth muscle in vitro

Specimens from aganglionic (constricted) and ganglionic (dilated) gut were obtained from nine patients with Hirschsprungs disease. Transmural nerve stimulation of ganglionic smooth muscle in vitro evoked an initial relaxation followed by a contraction. This contraction was reduced but not abolished by atropine and it was further reduced by substance P antagonists. Guanethidine did not affect the electrically evoked responses. In aganglionic smooth muscle, an atropine-sensitive contraction but no initial relaxation was registered. Tetrodotoxin abolished all responses to electrical stimulation in both ganglionic and aganglionic specimens. Application of carbachol or substance P produced contraction and the adrenergic agonist isoprenaline or vasoactive intestinal peptide produced relaxation in ganglionic as well as aganglionic specimens. Two other gut neuropeptides, neuropeptide Y and galanin, were without effect. The results do not indicate a different receptor set up in ganglionic v aganglionic gut. The results are compatible with a lack of noncholinergic nonadrenergic inhibitory neurons in the aganglionic gut.