Motility disorders of the gastrointestinal tract
http://www.100md.com
《美国医学杂志》
Division of Pediatric Gastroenterology & Nutrition, USA
Abstract
Over the past decades our knowledge of normal and abnormal gastrointestinal motility has increased tremendously. The availability of manometry to study bowel contraction patterns, laparoscopy to perform full thickness bowel biopsies for histological examination, have added to the investigative armamentarium and helped better diagnose motility disorders. However, the development of newer therapies for bowel motility disorders has been disappointingly slow. Newer modalities such as gastric and bowel pacing provides some hope for the future. In this article we have provided an overview of some of the common motility disorders in children and discussed their management.
Keywords: Gastroparesis; Intestinal Pseudo obstruction; Constipatic
Gastroparesis : This is a syndrome characterized by postprandial fullness, anorexia, early satiety, bloating, emesis, halitosis, and epigastric pain. The symptoms result from the impaired gastric emptying in absence of a mechanical obstruction. In children, delayed gastric emptying may be associated with diabetes mellitus, hypothyroidism, during the acute phase of a viral illness[1], eosinophilic gastroenteropathy, muscular dystrophy or after surgery and vagotomy.
The investigations to diagnose slow gastric emptying are generally unreliable in children. Barium studies help to exclude mechanical obstruction and may demonstrate very poor gastric emptying, but sensitivity and specificity is lacking. The Tc 99msub labeled solid food or liquid gastric emptying studies in children are fraught with shortcomings due to variability in technique and the effects of exam stress on emptying and therefore less often used in clinical assessment. Antroduodenal manometry may reveal hypomotility in the antrum and the duodenum or hypermotility such as tonic duodenal contractions and unremitting, constant bands of phasic duodenal contractions.[2],[3] Sonography in experienced hands can be used to evaluate gastric emptying in young infants[4]. The 13sub C-octanoic acid breath test is a newer, safe, nonradiologic test that can be used to measure gastric emptying using a liquid or solid meal.[5]
Treatment : The focus of management of children with gastroparesis should be (i) restoration of nutritional status, (ii) providing symptomatic relief from nausea and vomiting and (iii) therapies to improve gastric motility. Nutritional support is crucial as a majority of children are malnourished by the time the diagnosis is established. Enteral nutrition can be provided through a nasojejunal feeding tube, which bypasses the stomach. Once the stomach motility recovers oral feeds can be reinstituted. Ondansetron, low dose tricyclic antidepressants, promethazine and dronabinol (a cannabinoid) have been used to alleviate nausea, which can be a distressing symptom[6]. Prokinetics such as domperidone, metoclopramide and erythromycin may help improve gastric emptying. Tegaserod, a partially selective 5-HT4 receptor agonist improves gastric emptying and may be useful. Some reports suggest that patients with gastroparesis may have an abnormally high pyloric sphincter pressure, botulinum toxin injection into the pyloric muscle [7] and pyloric dilatation may help reduce the gastric outlet pressure, sometimes surgical pyloroplasty, pyloromyotomy or a feeding jejunostomy may be necessary.[8]
Chronic Intestinal Pseudo-obstruction
Chronic intestinal pseudo-obstruction (CIP) is a term which refers to a heterogeneous group of gastrointestinal nerve and muscle disorders with similar phenotypic presentation of obstructive intestinal symptoms.[9],[10],[11] Based on a strict definition of the syndrome, CIP should be diagnosed only when a mechanical obstruction has been ruled out. It is marked by repetitive episodes or continuous signs of bowel obstruction, often including radiographic evidence of dilated bowel with air-fluid levels, in the absence of a fixed lumen-occluding lesion.
Almost half of the patients develop symptoms in the neonatal period and 40% have associated intestinal malrotation. The commonest presenting symptoms are abdominal distension and vomiting are seen in almost 75 percent of patients; more than 60 percent have constipation, intermittent abdominal pain, and poor weight gain; and almost a third have diarrhea. Twenty percent of pediatric patients with neuropathic and 80 percent of those with myopathic pseudo-obstruction have associated urinary tract and bladder involvement. In most children with congenital disease, the clinical course has an illness plateau with intermittent worsening of symptoms. Triggers for acute decompensation include inter-current infections, general anesthesia, psychological stress, and poor nutrition. Nonspecific radiographic signs include air-fluid levels, and a dilated stomach, small intestine, and colon. Stasis of the contrast material in the affected loop may be prolonged, so evacuation or water-soluble contrast should be planned.
Autosomal-recessive and dominant patterns of inheritance have been reported in myopathic and neuropathic pseudo-obstruction.[9] CIP has been associated with fetal alcohol syndrome,[12] mitochondrial neurogastrointestinal encephalopathy[13] (MNGIE), cytomegalovirus, herpes zoster and Epstein-Barr virus infection and chromosomal abnormalities.[9] Autoimmune damage to the enteric nervous system has also been reported.[14]
Diagnosis : Intestinal pseudo-obstruction is a clinical diagnosis based on symptoms of bowel obstruction in the absence of an anatomical lesion. An enlarged urinary bladder may be seen on abdominal ultrasound. Manometric studies are used to evaluate strength and coordination of the gastric antrum, small intestine, and colon contractions.[15] Antroduodenal motility patterns in fasted, healthy humans are characterized by the cyclical, repetitive, strong phasic contractions and quiescence called the migrating motor complex (MMC).[16] The MMC consists of three patterns or phases: phase 1 is a period of motor quiescence, phase 2 is a period of irregular contractions, varying in amplitude, frequency and propagation and phase 3 is a distinctive pattern of regular, high amplitude contractions repeating at a maximal rate for several minutes, propagating from proximal to distal bowel. Each phase propagates proximal to distal. The normal digestive pattern in gastrointestinal motility is an irregular occurrence of contractions with various amplitudes. In subjects with visceral neuropathy, the contractions are uncoordinated but have normal amplitude. The MMCs are absent or replaced by prolonged clusters of non-propagating contractions. In children with visceral myopathy, manometry reveals persistent low amplitude but coordinated contractions. Antroduodenal manometry may also provide prognostic information and determine parts of the gastrointestinal tract involved by the disease.
Full thickness intestinal biopsies for routine histology, enzyme histochemistry and immunohistochemistry by light microscopy and ultra structural studies by electron microscopy may show evidence of neuropathy or enteric muscle disease.[17] In the past this required a laparotomy and was rarely performed, however, now full thickness bowel biopsies can be performed laparoscopically. In visceral myopathies there is degeneration of visceral smooth muscle accompanied by proliferation of collagen in the muscularis propria. Visceral neuropathies are characterized by degeneration changes in the myenteric plexus and loss of neurons and axons. In immune mediated damage to enteric nervous system, early treatment with immunosuppressives and corticosteroids may prevent full blown syndrome of intestinal pseudo-obstruction.[14], [17]
Treatment : One third of patients require parenteral nutrition; another one-third require enteral tube feeding support and the remainder are able to eat normally. If bolus feeding fails, continuous drip feeding through a nasogastric tube, a gastrostomy or jejunostomy should be initiated. Adequate nutrition is important to optimize gut neuromuscular function. During acute episodes, bowel decompression can be achieved by nasogastric tube drainage or a gastrostomy. Bowel decompression will help to relieve abdominal pain and vomiting. Chronic abdominal pain may respond to low-dose tricyclic antidepressants and gabapentin; narcotics disrupt motility and are not useful for chronic pain. Mineral oil, polyethelene glycol, suppositories, and/or enemas are used to treat constipation. Cisapride increases intestinal contractions and improves symptoms in a minority of patients and combined erythromycin and octreotide may improve bowel motility. Bacterial overgrowth may be treated with antibiotics or probiotics.[9] With irreversible intestinal failure and recurrent sepsis secondary to bacterial translocation, total enterectomy may be necessary. For life-threatening intestinal pseudo-obstruction, intestinal transplantation is a high-risk procedure with potential for cure. The quality of life for children with chronic intestinal pseudo-obstruction and their parents has not been as good as for other chronic diseases and may be improved by appropriate treatments for chronic pain, and attention to relieving each family's burden of time and emotional distress.
Hirschsprung's Disease : This is the commonest colon motility disorder in children and results from the absence of enteric ganglionic neurons, beginning at the anus and extending proximally for a variable distance. Racial distribution is equal for white and African American infants.[18] The more common rectosigmoid disease shows a male predominance of about 1:4. The majority of patients with Hirschsprung's disease present in the neonatal period with difficulty or delay in passing meconium, abdominal distension, bilious vomiting or enterocolitis. Barium enema may document a distal spastic aganglionic segment, the transition zone and proximal dilated colon. Barium enema examination is unreliable in infants and short segment disease.[19] In a majority of patients with short segment Hirschsprung's disease, a suction rectal biopsy with acetylcholine esterase staining to show hypertrophic nerve trunks in the muscularis mucosa is sufficient to make the diagnosis. If total colon aganglionosis is clinically suspected a normal acetylcholine esterase pattern on a suction rectal biopsy is insufficient to exclude Hirschsprung's disease and a full thickness surgical rectal biopsy should be performed to document aganglionosis in the myenteric and submucosal plexus. Anorectal manometry shows failure of the anal sphincter to relax in response to rectal distension. There are several syndromes associated with Hirschsprung's disease table1 and treatment is surgical resection of the aganglionic bowel segment.
Post-surgical problems in children with Hirschsprung's disease
After surgery for Hirschsprung's disease, 60 to 70 percent of children have continuing difficulties with defecation. About 10 percent continue to suffer from constipation due to a neuropathy proximal to the aganglionic segment.[20] Ganglion cells are present, but the connections are uncoordinated, and these patients have low amplitude, simultaneous contractions. Patients also continue to have an incomplete rectosphincteric inhibitory reflex-the hallmark of the disease-after surgery, facilitating the persistence of constipation. Other patients with constipation problems following successful surgery simply have functional fecal retention.
About half of patients with successful surgery have difficulties with fecal soiling that may last into adult life. The most common reasons for soiling are high amplitude propagating contractions which normally end in the sigmoid[21] continuing to propagate through the neorectum to the anus, because the storage area, the rectosigmoid, has been resected. Colon manometry clarifies the reasons for constipation and soiling following successful Hirschsprung's disease surgery. In patients with fecal soiling due to high amplitude propagating contractions through the neorectum, drugs such as loperamide and amitriptyline (0.2 mg/kg given at bed time) often firm up the stools and reduce soiling episodes as well as reduce the cramping pain associated with attempts to avoid soiling.
Colon Motility Disorders Other Than Hirschsprung's Disease
Constipation is a common problem in children and the majority have no underlying disease of the colon. This is also called 'functional constipation'. Discomfort during the passage of a hard and large stool may lead to fear of defecation, prompting retentive behavior. Children with this functional disorder who meet the pediatric Rome working team symptoms based criteria, need no further testing[22] and improve with the appropriate use of stool softeners and laxatives.[23]
Persistent constipation unresponsive to conventional medical management may be due to an underlying colon neuromuscular disorder. A good clinical history and appropriate investigations help differentiate colon neuromuscular problems from functional constipation table2. The pathologic diagnosis of neuromuscular colonic diseases is challenging due to the lack of age and location-matched control specimens. Infants and children with severe hyperganglionosis should be investigated for MEN 2B and the associated mutation within the RET -gene 24. Colonic transit studies using radio-opaque markers or scintigraphy techniques may be useful, but well defined normal values for children of different ages are lacking. In functional constipation, the markers accumulate in the rectum or are completely excreted but in colon neuromuscular disease they are scattered through out the colon or concentrated on the right side.[25] Colon manometry may also help in selecting patients with chronic intractable constipation who are not responding to standard laxative therapy and may benefit from surgical intervention.[26] Malone appendicocecostomy for antegrade colonic enemas may be useful in carefully selected patients.[27] This procedure connects the appendix to the umbilicus and uses the new orifice to administer an antegrade colonic enema (ACE) while the patient sits on the toilet. Using the ACE, the large bowel can be cleaned at regular intervals with irrigation solutions, such as tap water, polyethylene glycol, glycerin and saline. More recently, laparoscopic and percutaneous endoscopic cecostomy for antegrade enemas have also been used.[28]
Anal Achalasia
Internal anal sphincter achalasia or what has been previously called ultra short segment Hirschsprung's disease, is characterized by absent recto-anal inhibitory reflex during anorectal manometry and a normal rectal biopsy. Children with anal achalasia usually present with chronic constipation starting in infancy. Clostridium botulinum toxin injection into the anal sphincter[29] or anal sphincterotomy 30 have been used to relieve the symptoms.
References
1. Di Lorenzo C, Hyman PE, Flores AF et al. Antroduodenal manometry in children and adults with severe non-ulcer dyspepsia. Scand J Gastroenterol 1994; 29 : 799-806.
2. Cucchiara S, Bortolotti M, Colombo C et al. Abnormalities of gastrointestinal motility in children with nonulcer dyspepsia and in children with gastroesophageal reflux disease. Dig Dis Sci 1991; 36 : 1066-1073.
3. Cucchiara S. Ultrasound. In Hyman PE, DiLorenzo C (eds): Pediatric Gastrointestinal Motility Disorders . New York, Academy of Professional Information Services, 1994, pp 313-318.
4. Veereman-Wauters G, Ghoos Y, van der Schoor S et al. The 13C-octanoic acid breath test: a noninvasive technique to assess gastric emptying in preterm infants. J Pediatr 1997; 131 751-754.
5. Buckles DC, McCallum RW. Gastroparesis. In Theodore Bayless, Anna Mae Diehl (eds): Advanced Therapy in gastroenterology and Liver Disease , 5th Edition. Hamilton, Canada BCDecker Inc, 2004, pp190-5.
6. Bromer MQ, Friedenberg F, Miller LS et al. Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis. Gastrointest Endosc 2005; 61(7) : 833-839.
7. Okuyama H, Urao M, Starr GA et al. A comparison of the efficacy of pyloromyotomy and pyloroplasty in patients with gastroesophageal reflux and delayed gastric emptying. J Pediatr Surg 1997; 32 : 316-20.
8. Di Lorenzo C. Pseudo-obstruction: current approaches. Gastroenterology 1999; 116 : 980-987.
9. Hyman PE, Sood M. Chronic intestinal pseudo-obstruction. NORD Guide to Rare Disorders, 2002
10. Rudolph CD, Hyman PE, Altschuler SM et al. Diagnosis and treatment of chronic intestinal pseudo-obstruction in children: report of consensus workshop. J Pediatr Gastroenterol Nutr 1997; 24 : 102-112.
11. Uc A, Vasiliauskas E, Piccoli DA et al. Chronic intestinal pseudoobstruction associated with fetal alcohol syndrome. Dig Dis Sci 1997; 42 : 1163-1167.
12. Verma A, Piccoli DA, Bonilla E, Berry GT, DiMauro S, Moraes CT. A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy. Pediatr Res 1997; 42 : 448-454.
13. Smith VV, Gregson N, Foggensteiner L, Neale G, Milla PJ. Acquired intestinal aganglionosis and circulating autoantibodies without neoplasia or other neural involvement. Gastroenterology 1997; 112 : 1366-1371.
14. Cucchiara S, Borrelli O, Salvia G, Iula VD, Fecarotta S, Gaudiello G, Boccia G, Annese V. A normal gastrointestinal motility excludes chronic intestinal pseudoobstruction in children. Dig Dis Sci 2000; 45 : 258-264.
15. Uc A, Hoon A, Di Lorenzo C, Hyman PE. Antroduodenal manometry in children with no upper gastrointestinal symptoms. Scand J Gastroenterol 1997; 32 : 681-685.
16. Heneyke S, Smith VV, Spitz L, Milla PJ. Chronic intestinal pseudo-obstruction: treatment and long term follow up of 44 patients. Arch Dis Child 1999; 81 : 21-7.
17. Kleinhaus S et al. Hirschsprung's disease: A Survey of the Members of the Surgical Section of the American Academy of Pediatrics. J Pediatr Surg 1979; 14 : 588-597.
18. Swenson O, Davidson FZ, Similarities of the mechanical intestinal obstruction and aganglionic megacolon in the newborn infant: a review of 64 cases. N Engl J Med 1960; 262 : 64-67.
19. Di Lorenzo C, Solzi GF, Flores AF, Schwankovsky L, Hyman PE. Colonic motility after surgery for Hirschsprung's disease. Am J Gastroenterol 2000; 95 : 1759-1764.
20. Di Lorenzo C, Flores AF, Reddy SN, Hyman PE. Use of colonic manometry to differentiate causes of intractable constipation in children. J Pediatr 1992; 120 : 690-695.
21. Rasquin-Weber A, Hyman PE, Cucchiara S et al. Childhood functional gastrointestinal disorders. Gut 1999;45 Suppl 2 :I I60-168.
22. Baker S, Liptak GS, Colletti RB, et al. Constipation in Infants and Children: Evaluation and Treatment. J Pediatr Gastroenterol Nutr 1999; 29 : 612-626.
23. Cohen MS, Phay JE, Albinson C, DeBenedetti MK et al. Gastrointestinal manifestations of multiple endocrine neoplasia type 2. Ann Surg 2002; 235(5) : 648-654.
24. Papadopoulou A, Clayden GS, Booth IW. The clinical value of solid marker transit studies in childhood constipation and soiling. Eur J Pediatr 1994; 153(8) : 560-564.
25. Villarreal J, Sood M, Zangen T et al. Colonic Diversion for intractable constipation in children: colonic manometry guides clinical decision. J Pediatr Gastroenterol Nutr 2001; 33 : 588-591.
26. Griffiths DM, Malone PS. The Malone antegrade continence enema. J Pediatr Surg 1995; 30(1) : 68-71.
27. Rivera MT, Kugathasan S, Berger W, Werlin SL. Percutaneous colonoscopic cecostomy for management of chronic constipation in children. Gastrointest Endosc 2001; 53(2) : 225-228.
28. Ciamarra P, Nurko S, Barksdale E, Fishman S, Di Lorenzo C. Internal anal sphincter achalasia in children: clinical characteristics and treatment with Clostridium botulinum toxin. J Pediatr Gastroenterol Nutr 2003; 37 : 315-319.
29. De Caluwe D, Yoneda A, Akl U, Puri P. Internal anal sphincter achalasia: outcome after internal sphincter myectomy. J Pediatr Surg 2001; 36 : 736-738.(Venkatasubramani Narayana)
Abstract
Over the past decades our knowledge of normal and abnormal gastrointestinal motility has increased tremendously. The availability of manometry to study bowel contraction patterns, laparoscopy to perform full thickness bowel biopsies for histological examination, have added to the investigative armamentarium and helped better diagnose motility disorders. However, the development of newer therapies for bowel motility disorders has been disappointingly slow. Newer modalities such as gastric and bowel pacing provides some hope for the future. In this article we have provided an overview of some of the common motility disorders in children and discussed their management.
Keywords: Gastroparesis; Intestinal Pseudo obstruction; Constipatic
Gastroparesis : This is a syndrome characterized by postprandial fullness, anorexia, early satiety, bloating, emesis, halitosis, and epigastric pain. The symptoms result from the impaired gastric emptying in absence of a mechanical obstruction. In children, delayed gastric emptying may be associated with diabetes mellitus, hypothyroidism, during the acute phase of a viral illness[1], eosinophilic gastroenteropathy, muscular dystrophy or after surgery and vagotomy.
The investigations to diagnose slow gastric emptying are generally unreliable in children. Barium studies help to exclude mechanical obstruction and may demonstrate very poor gastric emptying, but sensitivity and specificity is lacking. The Tc 99msub labeled solid food or liquid gastric emptying studies in children are fraught with shortcomings due to variability in technique and the effects of exam stress on emptying and therefore less often used in clinical assessment. Antroduodenal manometry may reveal hypomotility in the antrum and the duodenum or hypermotility such as tonic duodenal contractions and unremitting, constant bands of phasic duodenal contractions.[2],[3] Sonography in experienced hands can be used to evaluate gastric emptying in young infants[4]. The 13sub C-octanoic acid breath test is a newer, safe, nonradiologic test that can be used to measure gastric emptying using a liquid or solid meal.[5]
Treatment : The focus of management of children with gastroparesis should be (i) restoration of nutritional status, (ii) providing symptomatic relief from nausea and vomiting and (iii) therapies to improve gastric motility. Nutritional support is crucial as a majority of children are malnourished by the time the diagnosis is established. Enteral nutrition can be provided through a nasojejunal feeding tube, which bypasses the stomach. Once the stomach motility recovers oral feeds can be reinstituted. Ondansetron, low dose tricyclic antidepressants, promethazine and dronabinol (a cannabinoid) have been used to alleviate nausea, which can be a distressing symptom[6]. Prokinetics such as domperidone, metoclopramide and erythromycin may help improve gastric emptying. Tegaserod, a partially selective 5-HT4 receptor agonist improves gastric emptying and may be useful. Some reports suggest that patients with gastroparesis may have an abnormally high pyloric sphincter pressure, botulinum toxin injection into the pyloric muscle [7] and pyloric dilatation may help reduce the gastric outlet pressure, sometimes surgical pyloroplasty, pyloromyotomy or a feeding jejunostomy may be necessary.[8]
Chronic Intestinal Pseudo-obstruction
Chronic intestinal pseudo-obstruction (CIP) is a term which refers to a heterogeneous group of gastrointestinal nerve and muscle disorders with similar phenotypic presentation of obstructive intestinal symptoms.[9],[10],[11] Based on a strict definition of the syndrome, CIP should be diagnosed only when a mechanical obstruction has been ruled out. It is marked by repetitive episodes or continuous signs of bowel obstruction, often including radiographic evidence of dilated bowel with air-fluid levels, in the absence of a fixed lumen-occluding lesion.
Almost half of the patients develop symptoms in the neonatal period and 40% have associated intestinal malrotation. The commonest presenting symptoms are abdominal distension and vomiting are seen in almost 75 percent of patients; more than 60 percent have constipation, intermittent abdominal pain, and poor weight gain; and almost a third have diarrhea. Twenty percent of pediatric patients with neuropathic and 80 percent of those with myopathic pseudo-obstruction have associated urinary tract and bladder involvement. In most children with congenital disease, the clinical course has an illness plateau with intermittent worsening of symptoms. Triggers for acute decompensation include inter-current infections, general anesthesia, psychological stress, and poor nutrition. Nonspecific radiographic signs include air-fluid levels, and a dilated stomach, small intestine, and colon. Stasis of the contrast material in the affected loop may be prolonged, so evacuation or water-soluble contrast should be planned.
Autosomal-recessive and dominant patterns of inheritance have been reported in myopathic and neuropathic pseudo-obstruction.[9] CIP has been associated with fetal alcohol syndrome,[12] mitochondrial neurogastrointestinal encephalopathy[13] (MNGIE), cytomegalovirus, herpes zoster and Epstein-Barr virus infection and chromosomal abnormalities.[9] Autoimmune damage to the enteric nervous system has also been reported.[14]
Diagnosis : Intestinal pseudo-obstruction is a clinical diagnosis based on symptoms of bowel obstruction in the absence of an anatomical lesion. An enlarged urinary bladder may be seen on abdominal ultrasound. Manometric studies are used to evaluate strength and coordination of the gastric antrum, small intestine, and colon contractions.[15] Antroduodenal motility patterns in fasted, healthy humans are characterized by the cyclical, repetitive, strong phasic contractions and quiescence called the migrating motor complex (MMC).[16] The MMC consists of three patterns or phases: phase 1 is a period of motor quiescence, phase 2 is a period of irregular contractions, varying in amplitude, frequency and propagation and phase 3 is a distinctive pattern of regular, high amplitude contractions repeating at a maximal rate for several minutes, propagating from proximal to distal bowel. Each phase propagates proximal to distal. The normal digestive pattern in gastrointestinal motility is an irregular occurrence of contractions with various amplitudes. In subjects with visceral neuropathy, the contractions are uncoordinated but have normal amplitude. The MMCs are absent or replaced by prolonged clusters of non-propagating contractions. In children with visceral myopathy, manometry reveals persistent low amplitude but coordinated contractions. Antroduodenal manometry may also provide prognostic information and determine parts of the gastrointestinal tract involved by the disease.
Full thickness intestinal biopsies for routine histology, enzyme histochemistry and immunohistochemistry by light microscopy and ultra structural studies by electron microscopy may show evidence of neuropathy or enteric muscle disease.[17] In the past this required a laparotomy and was rarely performed, however, now full thickness bowel biopsies can be performed laparoscopically. In visceral myopathies there is degeneration of visceral smooth muscle accompanied by proliferation of collagen in the muscularis propria. Visceral neuropathies are characterized by degeneration changes in the myenteric plexus and loss of neurons and axons. In immune mediated damage to enteric nervous system, early treatment with immunosuppressives and corticosteroids may prevent full blown syndrome of intestinal pseudo-obstruction.[14], [17]
Treatment : One third of patients require parenteral nutrition; another one-third require enteral tube feeding support and the remainder are able to eat normally. If bolus feeding fails, continuous drip feeding through a nasogastric tube, a gastrostomy or jejunostomy should be initiated. Adequate nutrition is important to optimize gut neuromuscular function. During acute episodes, bowel decompression can be achieved by nasogastric tube drainage or a gastrostomy. Bowel decompression will help to relieve abdominal pain and vomiting. Chronic abdominal pain may respond to low-dose tricyclic antidepressants and gabapentin; narcotics disrupt motility and are not useful for chronic pain. Mineral oil, polyethelene glycol, suppositories, and/or enemas are used to treat constipation. Cisapride increases intestinal contractions and improves symptoms in a minority of patients and combined erythromycin and octreotide may improve bowel motility. Bacterial overgrowth may be treated with antibiotics or probiotics.[9] With irreversible intestinal failure and recurrent sepsis secondary to bacterial translocation, total enterectomy may be necessary. For life-threatening intestinal pseudo-obstruction, intestinal transplantation is a high-risk procedure with potential for cure. The quality of life for children with chronic intestinal pseudo-obstruction and their parents has not been as good as for other chronic diseases and may be improved by appropriate treatments for chronic pain, and attention to relieving each family's burden of time and emotional distress.
Hirschsprung's Disease : This is the commonest colon motility disorder in children and results from the absence of enteric ganglionic neurons, beginning at the anus and extending proximally for a variable distance. Racial distribution is equal for white and African American infants.[18] The more common rectosigmoid disease shows a male predominance of about 1:4. The majority of patients with Hirschsprung's disease present in the neonatal period with difficulty or delay in passing meconium, abdominal distension, bilious vomiting or enterocolitis. Barium enema may document a distal spastic aganglionic segment, the transition zone and proximal dilated colon. Barium enema examination is unreliable in infants and short segment disease.[19] In a majority of patients with short segment Hirschsprung's disease, a suction rectal biopsy with acetylcholine esterase staining to show hypertrophic nerve trunks in the muscularis mucosa is sufficient to make the diagnosis. If total colon aganglionosis is clinically suspected a normal acetylcholine esterase pattern on a suction rectal biopsy is insufficient to exclude Hirschsprung's disease and a full thickness surgical rectal biopsy should be performed to document aganglionosis in the myenteric and submucosal plexus. Anorectal manometry shows failure of the anal sphincter to relax in response to rectal distension. There are several syndromes associated with Hirschsprung's disease table1 and treatment is surgical resection of the aganglionic bowel segment.
Post-surgical problems in children with Hirschsprung's disease
After surgery for Hirschsprung's disease, 60 to 70 percent of children have continuing difficulties with defecation. About 10 percent continue to suffer from constipation due to a neuropathy proximal to the aganglionic segment.[20] Ganglion cells are present, but the connections are uncoordinated, and these patients have low amplitude, simultaneous contractions. Patients also continue to have an incomplete rectosphincteric inhibitory reflex-the hallmark of the disease-after surgery, facilitating the persistence of constipation. Other patients with constipation problems following successful surgery simply have functional fecal retention.
About half of patients with successful surgery have difficulties with fecal soiling that may last into adult life. The most common reasons for soiling are high amplitude propagating contractions which normally end in the sigmoid[21] continuing to propagate through the neorectum to the anus, because the storage area, the rectosigmoid, has been resected. Colon manometry clarifies the reasons for constipation and soiling following successful Hirschsprung's disease surgery. In patients with fecal soiling due to high amplitude propagating contractions through the neorectum, drugs such as loperamide and amitriptyline (0.2 mg/kg given at bed time) often firm up the stools and reduce soiling episodes as well as reduce the cramping pain associated with attempts to avoid soiling.
Colon Motility Disorders Other Than Hirschsprung's Disease
Constipation is a common problem in children and the majority have no underlying disease of the colon. This is also called 'functional constipation'. Discomfort during the passage of a hard and large stool may lead to fear of defecation, prompting retentive behavior. Children with this functional disorder who meet the pediatric Rome working team symptoms based criteria, need no further testing[22] and improve with the appropriate use of stool softeners and laxatives.[23]
Persistent constipation unresponsive to conventional medical management may be due to an underlying colon neuromuscular disorder. A good clinical history and appropriate investigations help differentiate colon neuromuscular problems from functional constipation table2. The pathologic diagnosis of neuromuscular colonic diseases is challenging due to the lack of age and location-matched control specimens. Infants and children with severe hyperganglionosis should be investigated for MEN 2B and the associated mutation within the RET -gene 24. Colonic transit studies using radio-opaque markers or scintigraphy techniques may be useful, but well defined normal values for children of different ages are lacking. In functional constipation, the markers accumulate in the rectum or are completely excreted but in colon neuromuscular disease they are scattered through out the colon or concentrated on the right side.[25] Colon manometry may also help in selecting patients with chronic intractable constipation who are not responding to standard laxative therapy and may benefit from surgical intervention.[26] Malone appendicocecostomy for antegrade colonic enemas may be useful in carefully selected patients.[27] This procedure connects the appendix to the umbilicus and uses the new orifice to administer an antegrade colonic enema (ACE) while the patient sits on the toilet. Using the ACE, the large bowel can be cleaned at regular intervals with irrigation solutions, such as tap water, polyethylene glycol, glycerin and saline. More recently, laparoscopic and percutaneous endoscopic cecostomy for antegrade enemas have also been used.[28]
Anal Achalasia
Internal anal sphincter achalasia or what has been previously called ultra short segment Hirschsprung's disease, is characterized by absent recto-anal inhibitory reflex during anorectal manometry and a normal rectal biopsy. Children with anal achalasia usually present with chronic constipation starting in infancy. Clostridium botulinum toxin injection into the anal sphincter[29] or anal sphincterotomy 30 have been used to relieve the symptoms.
References
1. Di Lorenzo C, Hyman PE, Flores AF et al. Antroduodenal manometry in children and adults with severe non-ulcer dyspepsia. Scand J Gastroenterol 1994; 29 : 799-806.
2. Cucchiara S, Bortolotti M, Colombo C et al. Abnormalities of gastrointestinal motility in children with nonulcer dyspepsia and in children with gastroesophageal reflux disease. Dig Dis Sci 1991; 36 : 1066-1073.
3. Cucchiara S. Ultrasound. In Hyman PE, DiLorenzo C (eds): Pediatric Gastrointestinal Motility Disorders . New York, Academy of Professional Information Services, 1994, pp 313-318.
4. Veereman-Wauters G, Ghoos Y, van der Schoor S et al. The 13C-octanoic acid breath test: a noninvasive technique to assess gastric emptying in preterm infants. J Pediatr 1997; 131 751-754.
5. Buckles DC, McCallum RW. Gastroparesis. In Theodore Bayless, Anna Mae Diehl (eds): Advanced Therapy in gastroenterology and Liver Disease , 5th Edition. Hamilton, Canada BCDecker Inc, 2004, pp190-5.
6. Bromer MQ, Friedenberg F, Miller LS et al. Endoscopic pyloric injection of botulinum toxin A for the treatment of refractory gastroparesis. Gastrointest Endosc 2005; 61(7) : 833-839.
7. Okuyama H, Urao M, Starr GA et al. A comparison of the efficacy of pyloromyotomy and pyloroplasty in patients with gastroesophageal reflux and delayed gastric emptying. J Pediatr Surg 1997; 32 : 316-20.
8. Di Lorenzo C. Pseudo-obstruction: current approaches. Gastroenterology 1999; 116 : 980-987.
9. Hyman PE, Sood M. Chronic intestinal pseudo-obstruction. NORD Guide to Rare Disorders, 2002
10. Rudolph CD, Hyman PE, Altschuler SM et al. Diagnosis and treatment of chronic intestinal pseudo-obstruction in children: report of consensus workshop. J Pediatr Gastroenterol Nutr 1997; 24 : 102-112.
11. Uc A, Vasiliauskas E, Piccoli DA et al. Chronic intestinal pseudoobstruction associated with fetal alcohol syndrome. Dig Dis Sci 1997; 42 : 1163-1167.
12. Verma A, Piccoli DA, Bonilla E, Berry GT, DiMauro S, Moraes CT. A novel mitochondrial G8313A mutation associated with prominent initial gastrointestinal symptoms and progressive encephaloneuropathy. Pediatr Res 1997; 42 : 448-454.
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