Mucosal nerve deficiency in chronic childhood constipation: a postmigration defect?

Purpose

Idiopathic chronic childhood constipation (ICCC) includes children who are severely constipated and who are resistant to behavioral or medical treatments. These children are distinguished from those with Hirschsprung's disease (HSCR) by the presence of enteric ganglia in rectal biopsy specimens. We investigated potential autonomic dysfunction by examining nerves in rectal mucosa.

Methods

Immunostaining, confocal microscopy, and nerve analysis were performed on formalin-fixed and on Zamboni-fixed rectal biopsy specimens from children who were severely constipated. A computer-assisted neuron tracing technique was used to determine mucosal nerve density in Zamboni-fixed biopsy sections.

Results

Nerves in Zamboni-fixed biopsy specimens were better stained than in formalin-fixed biopsy specimens. Regardless of fixation method, a deficiency of mucosal nerves was observed in ICCC when compared to children who are not constipated. Analysis of autotraced mucosal nerves confirmed the deficiency in ICCC biopsy specimens. Mucosal nerves were also severely deficient in patients with HSCR, even in transitional segments that contained ganglia.

Conclusions

Most patients with ICCC had decreased innervation of the rectal mucosa. Because mucosal nerves are critical for the peristaltic reflex, water secretion, and absorption, their deficiency can be related to patient constipation. Mucosal nerve density provides a pathologic basis for diagnosis of dysfunction in children who do not have HSCR but are chronically constipated. The study validates the neuron tracing method for objective evaluation of mucosal innervation.     

Ultrashort Hirschsprung's disease: myth or reality

The term ultrashort Hirschsprung's disease has been used to define a spectrum of conditions with clinical presentation similar to Hirschsprung's disease but with presence of ganglion cells on rectal biopsy. In contrast to Hirschsprung's disease, there is no transition zone on barium enema. However, as in classical Hirschsprung's disease, there is no reflex internal sphincter relaxation on rectal manometry. We reviewed the presentation of five patients with chronic constipation who fulfilled the criteria for ultrashort Hirschsprung's disease. After positive anorectal manometry, despite the presence of ganglion cells on suction rectal biopsy, internal sphincter myomectomy was performed in four patients. Resolution of symptoms was noted in all operated patients. Normal ganglion cells were present throughout the entire length of all myomectomy specimens. There is controversy in the literature concerning the diagnosis of ultrashort Hirschsprung's disease. Most of the confusion concerns whether a short segment of aganglionosis proximal to the dentate line is permissible for the diagnosis of ultrashort Hirschsprung's disease and to what extent such aganglionosis is physiological. Perhaps it would be more accurate to define this entity by the presence of ganglion cells on rectal biopsy as well as the failure of the internal sphincter to relax on rectal manometry and to describe it as anorectal achalasia in severely constipated patients.     

The role of manometry, electromyography and radiology in the assessment of intractable constipation.

An analysis is made of functional studies performed in 96 constipated patients to see how these studies influenced the choice of surgical treatment. All patients underwent anal manometry, and other investigations included colonic transit studies (56), anal sphincter electromyography (42) and defaecatory proctography (34). Additionally nine patients underwent full thickness rectal biopsy. The resting anal canal pressures of the patients studied were lower than controls, and fibre density studies on electromyography were abnormal in half the patients studied suggesting a degree of denervation of the sphincter muscles, which possibly related to chronic straining on the toilet. There was evidence of reduced rectal sensation as shown by an increase in the least perceived volume on balloon distension of the rectum, and in those with megarectum and/or megacolon an increase in maximum tolerated volume. The recto-anal inhibitory reflex was used to screen for adult Hirschsprung's disease, but in one patient the reflex was present despite absence of ganglia on full thickness rectal biopsy indicating the need for biopsy as the definitive diagnostic procedure. Delayed colonic transit using radio opaque markers was a necessary requirement before recommending colectomy, and delayed transit was demonstrated in 34% of the patients studied. Anismus on electromyography was found in 20% of the patients but there was poor correlation with failure of the anorectal angle to widen when bearing down on proctography. The investigations helped in the choice of treatment, but were difficult to interpret. They should be used in severe constipation when surgery is being contemplated.     

THE ROLE OF MANOMETRY,ELECTROMYOGRAPHY AND RADIOLOGY IN THE ASSESSMENT OF INTRACTABLE CONSTIPATION

An analysis is made of functional studies performed in 96 constipated patients to see how these studies influenced the choice of surgical treatment. All patients underwent anal manometry, and other investigations included colonic transit studies (56), anal sphincter electromyography (42) and defaecatory proctography (34). Additionally nine patients underwent full thickness rectal biopsy. The resting anal canal pressures of the patients studied were lower than controls, and fibre density studies on electromyography were abnormal in half the patients studied suggesting a degree of denervation of the sphincter muscles, which possibly related to chronic straining on the toilet. There was evidence of reduced rectal sensation as shown by an increase in the least perceived volume on balloon distension of the rectum, and in those with megarectum and/or megacolon an increase in maximum tolerated volume. The recto-anal inhibitory reflex was used to screen for adult Hirschsprung's disease, but in one patient the reflex was present despite absence of ganglia on full thickness rectal biopsy indicating the need for biopsy as the definitive diagnostic procedure. Delayed colonic transit using radio opaque markers was a necessary requirement before recommending colectomy, and delayed transit was demonstrated in 34% of the patients studied. Anismus on electromyography was found in 20% of the patients but there was poor correlation with failure of the anorectal angle to widen when bearing down on proctography. The investigations helped in the choice of treatment, but were difficult to interpret. They should be used in severe constipation when surgery is being contemplated.     

The accuracy of transrectal aspiration biopsy of the prostate: an analysis of 452 cases

This study compares cytological findings obtained by transrectal aspiration biopsy of the prostate with histological findings obtained by simultaneously performed transperineal punch biopsy. All interventions were performed on outpatients. Complications such as hematuria, urinary infection, or epididymitis occurred in 4.4% of the cases, the majority of them being attributed to punch biopsies. Exact correspondence was found in 78.8% of 433 usable specimens, the accuracy for carcinoma amounting to 71.1%. Specimens cytologically judged either false "negative" or "suspicious" were histologically mostly well-differentiated (G1 and G2) carcinomas (96.1%). The value of fine needle biopsy of the prostate as nonstaining diagnostic procedure will be discussed.     

Sutured posterior abdominal rectopexy with sigmoidectomy compared with Marlex rectopexy for rectal prolapse

Two treatment policies for rectal prolapse were prospectively assessed between April 1986 and January 1989. Sixteen patients had a Marlex mesh posterior rectopexy alone and 13 underwent a sigmoidectomy combined with a sutured posterior rectopexy. Preoperative and post-operative assessment included manometry, a saline infusion test and video-proctography. Hospital stay, control of prolapse and complications were comparable in both groups. Restoration of continence occurred in nine of the 12 incontinent patients after Marlex rectopexy, compared with six of nine after sutured rectopexy and sigmoidectomy. Constipation persisted in three patients who were constipated before operation and in four of 13 who had previously normal bowel habits became constipated after Marlex rectopexy; constipation persisted in one of five previously constipated patients while none with previously normal bowel habits became constipated after sutured rectopexy and sigmoidectomy. Sigmoidectomy combined with sutured rectopexy was safe and as efficient as Marlex rectopexy in prolapse control and improvement of continence; significantly fewer patients were constipated (one of 13) after sigmoidectomy than following rectopexy alone (seven of 16). A randomized trial now seems justified.     

Idiopathic constipation associated with impaired urethrovesical and sacral reflex function

Sixteen chronically constipated women (age range 20-66 years) and 29 healthy control subjects (age range 22-53 years) underwent neurophysiological assessment of the integrity of pelvic spinal reflexes. The results were compared with videourodynamic studies and multiport anorectal manometry combined with external anal sphincter electromyography. The neurophysiological assessment consisted of electrical stimulation of the dorsogenital nerve, while recording any evoked reflex activity in the external anal and urethral sphincters with concentric needle and surface electrodes. Of these constipated women, 75 per cent had absence of one or more evoked sacral reflexes (compared with 20 per cent of healthy controls, P less than 0.05). Sensory thresholds and motor unit potentials in the external anal sphincter were similar in healthy and constipated women. Nine (56 per cent) constipated women displayed urodynamic abnormalities (increased bladder capacity, acontractile bladder and genuine stress incontinence). Only 38 per cent of constipated women perceived a desire to defaecate during rectal distension with up to 100 ml, compared with 95 per cent of normal subjects (P less than 0.0005). Moreover, 73 per cent of constipated women did not relax the external anal sphincter during defaecation, compared with 12 per cent of controls (P = 0.001). Taking into account the possible significance of our data in relation to previous findings it is suggested that the integration of sensory information within the sacral cord may be impaired in chronic idiopathic constipation.     

Internal anal sphincter achalasia: outcome after internal sphincter myectomy

BACKGROUND: Internal anal sphincter achalasia (IASA), also referred to as ultrashort segment Hirschsprung's disease (HD), is a clinical condition with presentation similar to HD, but with the presence of ganglion cells on rectal biopsy. The diagnosis of IASA is made on anorectal manometry, which shows the absence of rectosphincteric reflex on rectal balloon inflation. Altered intramuscular innervation has been reported in IASA. The purpose of this study was to review the outcome after internal sphincter myectomy in patients with IASA. METHODS: Fifteen consecutive patients (age range, 2 years to 12 years) with IASA underwent posterior internal sphincter myectomy. All patients presented with severe constipation with or without soiling. The diagnosis of IASA was made by anorectal manometry. HD was excluded in these cases by the presence of ganglion cells and normal acetylcholinesterase activity on suction rectal biopsies. Internal sphincter (IS) specimens were examined using immunohistochemistry for the general neuronal marker PGP 9.5 and synapsin 1 (a presynaptic marker) and using general histochemistry for NADPH-diaphorase. All patients underwent follow-up for periods from 2 years to 6 years. RESULTS: PGP 9.5, synapsin 1 and NADPH-diaphorase positive nerve fibers were either absent or markedly reduced in IASA specimens compared with controls, confirming previous reports of defective intramuscular innervation in IASA. At the time of follow-up, 7 patients have regular bowel motions and are not on any laxatives. Six patients have normal bowel habits but are on small doses of laxatives. One patient is able to stay clean with regular enema regimen. One patient required resection of dilated and redundant sigmoid colon and now has normal bowel habits with laxatives. CONCLUSION: The majority of patients with internal anal sphincter achalasia can be treated successfully by internal sphincter myectomy.     

Diagnostic scoring system of Hirschsprung's disease in the neonatal period

OBJECTIVE: Eighty to ninety percent of Hirschsprung's disease (HD) patients present in newborns. However, the diagnosis of HD in the neonatal period remains difficult. Our present study aims to propose a diagnostic scoring system and hope this will increase early diagnosis of HD and avoid unnecessary rectal biopsy. METHODS: In the first study period, 57 suspected HD patients (0-3 months) completed our predetermined study protocol in which barium enema (BE), rectal manometry (RM) and full-thickness rectal biopsy were performed. Symptoms, signs and investigations were analysed for their correlation with HD diagnosis. A HD diagnostic scoring system was developed according to the statistical results and was assessed in 74 patients in the second study period. RESULTS: Forty-five patients were diagnosed with HD in the first study period. A HD scoring system was developed in which delayed meconium, tight anus, BE and RM were diagnostic factors. A cut-off point of 3 provided 84% of HD patients score >3, whereas 75% non-HD patients score 相似文献   

Anteroposterior rectopexy for disorders of rectal stasis: clinical and radiologic results. Value of digital subtraction rectography. Apropos of 30 cases

We report the results of 30 antero-posterior rectopexies (APR) for rectal kinetic disorders with descending perineum syndrome. All patients were investigated by digital subtraction defecography and ano-rectal manometry. The associated surgical procedures were: sphincterotomy (n = 13) for outlet obstruction demonstrated by anal manometry or balloon expulsion test: hypertonic sphincter (n = 7), narrow fibrous sphincter (n = 6); 10 cases of prolapsectomy with extended anterior mucosectomy to reduce anterior rectal prolapse; 2 sigmoidectomy for dolichosigmoid. Best results (mean follow-up: 12 months, 3-26) were observed for ano-rectal or pelvic pain and rectal bleeding, which were cured in more than 80% of cases. Faecal incontinence (n = 5) was cured in all cases. Although normalisation of bowel movements and easier defecation were observed in 78% of cases, improvement in the dyschezic syndrome was differently perceived by the patients. Postoperative investigation demonstrated the probable cause of surgical failures (23%): impairment of rectal sensitivity (n = 2), anismus (n = 3), motor constipation (n = 4), with dolichosigmoid (n = 3). Severe perineal deficiency was also noted in 4 cases. Solitary ulcer (n = 6), anterior proctitis (n = 8), were cured within 2 months. Postoperative defecography showed correction of rectal intussusception without impairment of anterior rectal motility during defecation. These results confirm the efficacy of ARP for treatment of rectal intussusception or anterior rectocele. This functional rectopexy avoids the rectal "sling effect" of standard rectopexy which usually increases rectal dysfunction. Nevertheless, ARP alone seems to be insufficient when the associated functional or organic disorders implicated in rectal dysfunction are not also corrected, essentially outlet obstruction and dolichosigmoid.     

Megarectum after surgery for anorectal malformations

Purpose

Megarectum complicating surgery for anorectal malformation (ARM) has implications for long-term continence. Factors influencing continence and defecation include intact rectal reservoir, innervation/proprioception of the anorectal muscle complex, functioning anorectal inhibitory reflex (AIR), and intact perception at the anal margin. We studied outcomes after surgery for ARM with emphasis on megarectum; particularly as to whether altered rectal proprioception from anatomic sacrococcygeal anomalies affect incidence. We also assessed whether an abnormal AIR could trigger passive rectal dilatation without mechanical obstruction.

Methods

Eighty six infants (53 male) with ARM over 20 years were included. Demographics, surgical history, pathology, defecation patterns, imaging, manometry, and morbidity were analyzed. Incidence of sacrococcygeal malformations in children with and without megarectum was compared using Fisher exact test. Manometry results were evaluated for integrity of AIR and correlated to megarectum occurrence.

Results

There were 23 high/intermediate and 63 low ARMs. Fourteen (16%) developed a megarectum: 6 of 23 in high and 8 of 63 in low anomalies (P = .33). Twelve patients underwent megarectum resection at a median of 2.6 years (7 months to 10 years); 2 received bowel management protocols. Fifty-seven percent (8/14) of children with and 7% (5/72) without megarectum had sacrovertebral anomalies (P = .0001). Patients with preoperative manometry (n = 5) demonstrated an intact AIR. Colonic manometry demonstrated hyperactive colons (n = 2). Constipation was the predominant preoperative symptom; 3 patients suffered from incontinence after resection. All the specimens showed normal innervation and thickened muscularis on pathology.

Conclusions

Sacral anomalies, which are more prevalent in children who developed megarectum, may result in abnormal rectal proprioception contributing to this pathology. Innervation anomalies may coexist, although preoperative manometries showed normal AIRs. Rectal dysmotility may lead to stool retention with subsequent dilatation, and patients who underwent colonic manometry had diffuse colonic hypermotility. Further physiologic and cellular studies are needed to elucidate the causes of this significant complication after surgical ARM repair in the absence of obstruction.     

Comparison of the Tru-cut biopsy needle with the Abrams punch for pleural biopsy.

In a prospective study pleural biopsy specimens obtained with a Tru-cut needle were compared with those obtained with an Abrams pleural biopsy punch from 36 patients in Zimbabwe judged to have an effusion of at least 1.5 litres; one patient had two biopsies. Both instruments were used on each patient, the Abrams punch being followed by the Tru-cut needle. There were no serious complications. The diagnoses determined by biopsy were: tuberculosis (11); carcinoma (12); chronic inflammation (9); and pleural fibrosis (4); one biopsy showed nothing abnormal. In 23 (62%) patients both biopsy needles produced adequate diagnostic material; in eight the Tru-cut needle alone produced diagnostic material and in six the Abrams punch alone. Thus diagnostic material was obtained in 31 patients from the Tru-cut needle and in 29 from the Abrams punch. The Tru-cut needle was useful and safe for pleural biopsy in this series and appeared to be particularly useful when the pleura was thickened.     

Problems and advantages of acetylcholinesterase histochemistry of rectal suction biopsies in the diagnosis of Hirschsprung's disease

One hundred fifty-seven children, aged 2 days to 15 years, had rectal biopsies for suspected Hirschsprung's disease from 1980 to 1987. Sixty had adequate suction rectal biopsies stained for acetylcholinesterase (ACE); 41 of these were reported as normal and eight showed atypical innervation in children who progressed satisfactorily without surgery. Two showed hyperganglionosis and nine were from children with Hirschsprung's disease. Four of the latter nine biopsies (44%) gave false-negative results in infants aged 9, 10, 13 days, and 6 weeks. The last had total colonic aganglionosis. There were two false-positive results, one in a normal child with atypical innervation and the other in a child with hyperganglionosis. Thus, six of 60 (10%) of ACE-stained suction rectal biopsies gave misleading results.     

Colonic atresia and Hirschsprung's disease: importance of histologic examination of the distal bowel

Hirschsprung's disease associated with colonic atresia is rare. A boy with colonic atresia at the hepatic flexure who had a colostomy in the neonatal period suffered from severe constipation after definitive colocolostomy. Hirschsprung's disease was diagnosed with anorectal manometry and rectal mucosal biopsy, and a Duhamel-Ikeda's pull-through procedure was performed. Aganglionosis of the entire distal colon was seen, and intrauterine torsion of the dilated proximal colon followed by necrosis and absorption was suspected as the cause of colonic atresia. Colonic atresia should be generally screened for Hirschsprung's disease with a rectal biopsy. J Pediatr Surg 37:E19.     

Acetylcholinesterase activity in rectal mucosa and blood in the diagnosis of Hirschsprung's disease

Histochemical and biochemical examinations of rectal biopsy specimens were performed in 13 patients with Hirschsprung's disease and in seven with idiopathic constipation and no megacolon. Serum and erythrocyte acetylcholinesterase (AchE) activity in these two groups was compared with that in 30 normal controls. AchE staining of rectal biopsy specimens proved to be a reliable and convenient diagnostic approach in patients with Hirschsprung's disease. Biochemical assay of AchE activity in rectal biopsy specimens was also of value in the diagnosis, however, there was an overlap between Hirschsprung's disease and idiopathic constipation. Erythrocyte AchE activity correlated well with AchE activity in rectal biopsy specimens. Therefore, assays of erythrocyte AchE activity provided useful additional information, especially in screening tests for Hirschsprung's disease.     

The expanding utility of endoluminal ultrasonography in the management of rectal cancer.

BACKGROUND. This study assessed the ability of endoluminal ultrasonography (ELUS) to determine extent of local invasion and lymph node (LN) metastasis of primary rectal tumors, to assist in ELUS-guided pelvic LN biopsies, and to assess invasion of locally recurrent rectal cancers compared to computed tomography (CT). METHODS. Eighty-one patients with rectal adenocarcinoma (n = 67) or villous adenoma of more than 3 cm (n = 14) underwent ELUS with a 360-degree 7.0-MHz transducer For LN biopsy (n = 10), ELUS was used with an 18-gauge core biopsy needle passed transrectally. ELUS and CT were compared in 14 locally recurrent tumors. RESULTS. Staging for primary tumors (ELUS compared with pathologic examination, TNM system) revealed ELUS accurately predicted wall penetration and LN status with 95% confidence intervals of 0.88 to 0.99 and 0.87 to 0.99. Eight cancers were overstaged, and two were understaged by ELUS. ELUS-guided LN biopsy revealed carcinoma (n = 3) or lymphoid tissue (n = 3) in six of 10 patients. Extent of pelvic organ involvement was predicted in 11 of 14 ELUS and eight of 14 CT examinations in recurrent rectal cancer. CONCLUSIONS. ELUS is accurate in staging rectal cancers, can guide biopsies of pararectal LNs, and may be more reliable than CT in assessing local recurrence. The role of ELUS in the management of rectal cancer is expanding.     

Is the Colposcopically Directed Punch Biopsy a Reliable Diagnostic Test in Women With Minor Cytological Lesions?

OBJECTIVE: The study aimed to determine the accuracy of the colposcopy-directed punch biopsy (punch) to detect or exclude high-grade cervical intraepithelial neoplasia (CIN 2 or 3) in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytological result and minor colposcopic findings. MATERIALS AND METHODS: In a diagnostic test accuracy study, women with ASCUS or LSIL cytological result and minor colposcopic changes had a single colposcopy-targeted punch biopsy was performed immediately followed by a loop electrocautery excision procedure (LEEP) biopsy. The trial was powered to detect a level of κ for a dichotomous outcome of 0.4 (i.e., fair-to-moderate agreement), with a two-sided significance level of 5% and a power of 90%. Accuracy parameters were computed using a cutoff for positive punch biopsy result of CIN 1+ and CIN 2+ for an outcome of CIN 2+ and CIN 3+ assessed in the LEEP specimen. RESULTS: Sixty-eight punch biopsy/LEEP-paired samples were analyzed. Of the 8 CIN 3 lesions, 6 and 4 were detected at cutoff CIN 1+ and CIN 2+, respectively (sensitivity, 50% and 75%). The corresponding specificities were 65% (39/60) and 97% (58/60). The punch biopsies identified only 14 (67%) or 6 (20%) of the 21 CIN 2+ lesions at cutoff CIN 1+ or CIN 2+, respectively. Of the punch biopsies, 31 (45.6%) accurately detected the severity of cervical abnormality. CONCLUSIONS: A single colposcopically directed punch biopsy appears to be insufficient to exclude underlying CIN 2 or 3.     

Diagnosis of mediastinal masses in pediatric patients using mediastinoscopy and the Chamberlain procedure

BACKGROUND/PURPOSE: Mediastinal masses commonly are referred to the pediatric surgeon and can be difficult diagnostic problems. Various techniques have been used to perform biopsy in the mediastinum, but there are few reports of mediastinoscopy or Chamberlain procedure in children in the literature. The authors reviewed their experience with these techniques in a pediatric oncology population. METHODS: The medical records of all patients on the pediatric surgical service between 1987 and 1997, inclusive, who underwent mediastinoscopy or Chamberlain procedure were reviewed. Demographic data, diagnostic accuracy, complications, operating time, and blood loss were recorded. RESULTS: Sixteen consecutive patients underwent 13 Chamberlain procedures and six mediastinoscopies over the above period. Diagnostic accuracy was found to be 95% overall (100% for Chamberlain procedure, 83% for mediastinoscopy). Five complications occurred in the Chamberlain group and none in the mediastinoscopy group. No complication required thoracotomy or sternotomy. Among patients whose sole reason for admission was diagnosis of a mediastinal mass, the mean hospital stay was 1.7+/-0.8 days (n = 7) for those who underwent Chamberlain procedure and 1.4+/-0.9 days (n = 4) for those who underwent mediastinoscopy. One mediastinoscopy was performed as an ambulatory procedure. CONCLUSION: Mediastinoscopy and the Chamberlain procedure are effective and safe techniques for biopsy of mediastinal masses in this age group.     

Predicting preoperatively the outcome of respiratory symptoms of gastroesophageal reflux.

The fact that bronchopulmonary symptoms remain unchanged in about 15% of patients after successful operation for gastroesophageal reflux (GER) with respiratory tract disease (RTD) makes surgical indications uncertain and warrants further research into preoperative prognostic predictors. This problem has been addressed in infants by demonstrating that those most likely to be cured by antireflux procedures have long nocturnal episodes of GER and/or temporal coincidence between drops in pH levels and respiratory episodes. In an attempt to validate these predictors and, at the same time, to search for other reliable ones, we have retrospectively studied the charts, manometric studies, pH tracings, and pathology reports of 55 patients aged 48 +/- 36 months (range, 2 to 170) who had Nissen funduplication for GER with RTD in the last 10 years. Forty-five children were cured or improved of their RTD symptoms after operation, but in 10 (18%) they were unchanged in spite of the control of GER. Patients with a former history of vomiting (n = 38) had better results than those (n = 17) without it (95% of RTD cure v 53%, P less than .001). The success rate in children with recurrent obstructive airway disease (n = 20) was definitely lower than in those without it (n = 35) (70% v 89%, P less than .05). Neither esophageal manometry nor mucosal biopsy provided any predictive clue, but pH studies confirmed that the mean duration of nocturnal episodes of reflux (ZMD) was definitely longer in patients responding favourably to surgical cure of GER than in those in whom this failed (12.2 +/- 9.6 v 3.9 +/- 2.8 minutes, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)