Updated results on intestinal neuronal dysplasia (IND B).

BACKGROUND: Intestinal neuronal dysplasia (IND B) is still a subject of controversy. The aim of this paper is to review the present state of knowledge on IND B. A summary is given of the technical and diagnostic criteria which have to be considered in order to arrive at a reliable diagnosis. In addition, the available therapeutic interventions are discussed. METHODS: Between 1992 and 2001, 3984 colonic mucosal biopsies from 1328 children were investigated. Nerve cell staining was performed on native tissue sections: 15 microm thick cryostat sections, which, after spreading and drying on a microscopic slide, have a final thickness of 4-5 microm, with dehydrogenase reactions (lactic dehydrogenase, nitroxide synthase, succinic dehydrogenase). The biopsies were taken 8-10 cm above the dentate line (proximal to the ampulla recti, because of the caudo-cranial increase of giant ganglia proximal to the 4 cm biopsy) with a sufficient amount of submucosa. The criteria for IND is 15-20 % submucosal giant ganglia with more than eight nerve cells in 30 sections of a single biopsy (i.e. four to seven giant ganglia). RESULTS: The diagnosis of IND B is quantitative. A diagnosis of IND B was made over the past 10 years in 51 Hirschsprung resections (about 5 per year; 6 % of all Hirschsprung cases), and in 92 children with chronic constipation (about 9 children per year; 2.3 % incidence). Up to their fourth year of life, most children with isolated IND can be treated conservatively. This is due to the delayed maturation of the enteric nervous system which is characteristic of IND B. Only children who showed an additional hypoplastic hypoganglionosis were treated surgically. Children with Hirschsprung's disease (HD) and IND B proximal to the aganglionosis often showed, in those cases with a disseminated IND, postoperative disturbances in intestinal motility. CONCLUSION: The diagnosis of IND B requires that biopsies are taken proximal to the ampulla recti (about 8-10 cm above the dentate line) with a sufficient amount of submucosa. The biopsies must be cut rectangular to the surface of the mucosa. A diagnosis of IND B can be made only if, in the submucosa of 30 serial sections, 15-20 % of all ganglia are giant ganglia with more than eight nerve cells. Ganglioneuromatosis (MEN2B) must be clearly differentiated from IND. The clinical course of IND B depends on the extent of disturbed bowel innervation, the severity of motility failure, and the coexistence of MH. The conservative management of isolated IND is possible in most children. In individual cases, however, a transient enterostomy or a segmental resection is unavoidable.

Subnational sources of toxicology information: state, territorial, tribal, county, municipal, and community resources online.

The rapid assimilation data and information on the Internet and the World Wide Web (WWW) is reflected in the development of these electronic services by state, county, local, and other subnational agencies, departments, offices, bureaus, and intergovernmental bodies. The content of state and territorial, tribal, county, and local government Web pages varies considerably. However, information about health and the environment are among the most frequently posted resources by subnational government bodies. This article describes the environmental health and toxicology-related data and information resources provided by government agencies and representative associations for subnational government bodies. Standard reference sources for identifying subnational government bodies are described with particular reference to those in electronic and digital formats. Means for identifying and locating electronic resources are described for appropriate subnational environmental quality, environmental (public) health agencies, occupational health and safety, toxicology-related agencies and departments, emergency response, fish consumption advisories, and cancer registries are provided. Professional organizations of state, county, municipal (local) governments and intergovernmental bodies are also described.

Embolism of a metallic clip: an unusual complication following laparoscopic cholecystectomy.

A 32-year-old woman underwent laparoscopic cholecystectomy during which there was severe bleeding from the bed of the gallbladder. As application of metallic clips to control the bleeding was not successful, the operation was converted to an open laparotomy. Cholecystectomy was successfully completed without further complications, and the post-operative course was uneventful and the patient was discharged. Eighteen months later, the patient complained of dyspnea. Plain radiograph and computed tomography of the thorax showed a metallic clip in the branch of the pulmonary artery supplying the posterior basal segment of the inferior lobe of the left lung. There was no connection between the patient's symptoms and the clip embolism. Nevertheless, clip migration or embolism could cause severe complications. Therefore, metallic clips should not be used to stop bleeding from the gallbladder bed.

[Retractile mesenteritis after resection of Meckel's diverticulum]. / Retraktile Mesenteritis nach Resektion eines Meckelschen Divertikels.

HISTORY AND ADMISSION FINDINGS: A 22-year-old man who had never been seriously ill previously was admitted because of epigastric pain and vomiting of bile. INVESTIGATIONS: He had slight pain on pressure over the epigatric region and decreased intestinal peristaltic sounds. There was evidence of ileus of the small intestine both by ultrasound and radiologically. TREATMENT AND COURSE: As the patient's condition deteriorated on conservative treatment, an exploratory laparotomy was performed. It revealed an invaginated Meckel's diverticulum, Ileus of the small intestine recurred postoperatively, requiring relaparotomy. A glued-together volvulus of the small intestine had to be resected, even though there was no sign of an anastomotic leak. But there was no postoperative improvement. A third operation revealed a clearly shortened and 3 cm-thick mesentery which showed a stage III retractile mesenteritis. Histological re-examination of the specimens resected at the previous operations revealed stage I and II retractile mesenteritis. The patient's condition slowly improved on high doses of corticosteroids and he ultimately became symptom-free. CONCLUSIONS: Retractile mesenteritis is a very rare benign disease of the mesentery, almost always causing abdominal pain and diagnosed histologically by exploratory laparotomy. Administration of corticosteroids is the treatment of choice.

[Intestinal neuronal dysplasia in adults as a cause of chronic constipation: morphometric characterization of colon innervation]. / Intestinale neuronale Dysplasie des Erwachsenen als Ursache der chronischen Obstipation. Morphometrische Charakterisierung der Coloninnervation.

Intestinal neuronal dysplasia (IND) was initially described as a developmental abnormality of the submucous plexus in children. In recent years this abnormality has also been observed in adults with chronic constipation. The aim of this study was a morphometric characterization of this disease. The investigation was performed with 10 adults with IND, compared with 10 healthy control probands. The best diagnostic indicator of IND proved to be the detection of 6-10 giant ganglia with more than 7 nerve cells in 15 biopsy sections. IND is an interesting cause of chronic constipation which can be histologically verified.

Histopathological criteria for intestinal neuronal dysplasia of the submucosal plexus (type B)

The aim of this study was to review critically the diagnostic features of intestinal neuronal dysplasia type B (IND B). Over a period of 5 years colonic mucosal biopsies of 773 children with symptoms of chronic constipation were examined. Four biopsies taken 2-10 cm above the pectinate line were cut in serial sections and histochemical lactate dehydrogenase, succinate dehydrogenase, (SDH) and acetylcholinesterase (AChE) reactions performed. Presence of giant ganglia of the submucosal plexus, being characterized by more than seven nerve cells, established the diagnosis of IND B. Giant ganglia were found to be age-independent changes, while hyperplasia of the submucosal plexus, increase of AChE activity in nerve fibres of the lamina propria and low SDH activity in nerve cells proved to be age-dependent findings which disappear during the maturation of the enteric nervous system. Using these criteria IND B was diagnosed in 209 children. In 64 of these patients a combination of IND B and aganglionosis (Hirschsprung's disease) was found. IND B seems to be related to premature expression of laminin A during embryogenesis, resulting in premature nerve cell differentiation in the myenteric and submucosal plexus, which in turn blocks neuroblast colonization of the rectum. IND B, hypoganglionosis and aganglionosis, which are often combined, may therefore be considered to be different manifestations of the same developmental abnormality.

Experience with neuronal intestinal dysplasia (NID) in adults.

In paediatrics neuronal intestinal dysplasia (NID) has frequently been described, but in adults the clinical picture was not recognised. NID has been diagnosed in adults as well as children with impaired colonic motility since enzymehistochemical methods became available. Patients with primary chronic constipation (n = 41) and with diverticulosis of the sigmoid colon (n = 23) showed neuronal colonic dysplasia, whereas healthy controls (n = 15) had a normal innervation of the intestinal wall (p < 0.001). The results of this clinical study make a worthwile contribution to the understanding of the aetiology and pathogenesis of primary chronic constipation and diverticulosis of the colon in adults. Conservative treatment is usually unavailing and surgical intervention is needed. Hence, where strictly indicated, resection of the pathologically disturbed colon segment is often the only successful therapeutic procedure.

Epithelial misplacement after biopsy of colorectal adenomas.

The question has been raised as to whether the removal of biopsy material from colorectal adenomas can lead to misplacement of tumour fragments into the deeper layers of the bowel wall. We carried out an analysis of histological sections obtained from 21 patients in whom, between 2 and 21 days before removal of their adenoma, forceps biopsy (n = 18), or polypectomy (n = 3) had been performed. The initial histological picture a few days after biopsy is of an ulcer covered by a suppurative exudate and abundant mucus-containing small, free-lying groups of tumour cells. After an average of 7 days, we found misplacement of these groups of cells into the submucosa where, during the course of reparative processes, they became embedded within a capillary-rich granulation tissue. Subsequently, fibrosis of the submucosa develops with persistent mucus pools. Our results thus show that removal of biopsy material from adenomas can result in misplacement of tumour particles into the submucosa. These changes were observed in flat or broad-based tumours, and epithelial misplacement appears to be detectable within only a short period after biopsy. For the differential diagnosis, it is important to distinguish these changes from invasive carcinoma.

[Neuronal colon dysplasia in adulthood. Diagnosis, clinical aspects and therapy]. / Die neuronale Kolondysplasie im Erwachsenenalter. Diagnostik, Klinik und Therapie.

In patients with primary chronic constipation (n = 18) and diverticulosis of the sigmoid (n = 17) biopsies were examined enzyme-histochemically and the diagnosis of neuronal colonic dysplasia of the rectosigmoid was established. In eleven controls however a normal innervation was observed (p less than 0.001). Patients with neuronal colonic dysplasia usually failed to respond to conservative methods of treatment. Indication for surgery depended upon the duration and severity of the symptoms. The actual treatment--partial lateral submucous sphincterotomy, resection of the sigmoid colon or subtotal colectomy--was determined by the extent of the morphologically and functionally altered intestinal segment.

The cholecystogastric fistula.

Internal gall bladder fistulas with a hollow viscus following dislocation of a gallstone into the intestine represent one of the late sequelae of cholelithiasis. We report the case of a 78-year-old patient, who suffered from a cholecystogastric fistula with consecutive stone transmigration into the stomach.

Diagnosis of neuronal colonic dysplasia in primary chronic constipation and sigmoid diverticulosis endoscopic biopsy and enzyme-histochemical examination.

Neuronal colonic dysplasia is a separate clinical entity belonging to the group of congenital defects of intestinal innervation. Its enzyme-histochemical diagnosis is possible by endoscopic biopsy examination of the rectosigmoid. Enzyme-histochemically, it is characterized by dysplasia of the submucous plexus secondary to developmental defects. The principal clinical feature is weak propulsive motility. A clinical study was carried out to investigate the role of neuronal colonic dysplasia in the aetiology and pathogenesis of primary chronic constipation and diverticulosis of the sigmoid colon in adults.

Investigations of the muscular architecture of the rectosigmoid junction in humans.

The rectosigmoid junction, the segment of the gut where the colon merges with the rectum, has characteristic morphologic features and specific functional significance. The purpose of this study was to investigate the precise morphology of the musculature of this junction as a preliminary step toward closer study of its function and a better understanding of intestinal motility. To this end, the topographic relations of the rectosigmoid junction were investigated in specimens from 39 human cadavers. Although these relations varied, in all cases the rectosigmoid was located intraperitoneally and was distal to the promontory of the sacrum. Examination of muscle specimens under the dissecting microscope revealed conspicuous bands of longitudinal fibers, with curved interconnections between the longitudinal and circular muscle coats. The rectosigmoid junction is not a true sphincter, although in functional terms it can be regarded as such.

Neuronal dysplasia. Considerations for the pathogenesis and treatment of primary chronic constipation in adults.

Intestinal muscle and the autonomic nervous system constitute a neuromuscular unit. A clinical study was undertaken to seek neurogenic causes of impaired motility affecting the rectosigmoid junction and rectum. Patients with primary chronic constipation were shown by enzyme-histochemical examination of biopsies to have neuronal colonic dysplasia of the rectosigmoid, whereas the latter was normally innervated in healthy controls. The present investigations provide a fresh insight, underpinned by histological findings, into the aetiology of chronic constipation and make a contribution to its operative treatment.

Measuring of immunoreactivity of carcinoembryonic antigen (CEA) in colorectal cancer by microdensitometry.

In 32 patients with colorectal carcinomas, the immunoreactivity of carcinoembryonic antigen (CEA) was measured on section preparations of the tumours by means of a computer controlled microdensitometric method. By measuring numerous single points, the intensity of the immunohistochemical staining reaction of CEA was evaluated. This method is superior to the commonly used semiquantitative method (+, ++, ) for the assessment of various degrees of staining intensity whenever the antigen to be measured is not homogeneously dispersed in the tissue. The results show that highly differentiated colorectal carcinomas of stage A according to Dukes classification have a lower CEA immunoreactivity than highly differentiated carcinomas of stage B. A correlation between CEA immunoreactivity and degree of malignancy could only be found in patients in stage B. Stage C carcinomas of all degrees of differentiation appeared with a very low CEA immunoreactivity. CEA follow-up controls in our study were of little value for detecting local recurrences; metastases, however, almost always caused an increase in serum CEA titers. Prognostically, a preoperatively increased serum CEA level seems to be as unfavourable as a low CEA immunoreactivity in the tumour.

[Reflections on the significance of detecting Campylobacter pylori in a biopsy of the stomach mucosa]. / Uberlegungen zur Bedeutung des Nachweises von Campylobacter pylori in der Magenschleimhautbiopsie.

The inevitable confrontation with Campylobacter pyloridis implicates the surgeon to take into consideration this germ. For that reason we have examinated Campylobacter-positive patients with regard to histological changes of the gastric mucosa and to clinical symptoms. Apart from the fact, that there was no Campylobacter colonisation in the healthy gastric mucosa, there were not found specific features for the germ.

Endoscopic decompression in "toxic megacolon".

Endoscopic decompression of the bowel in "toxic megacolon" is presented in two cases as an alternative procedure to Turnbull's technique using multiple bowel fistulas. In our opinion this technique seems to be a substantial improvement in the treatment of "toxic megacolon" and may even help to prevent ileotomy-colotomy in some cases.