- Email: [email protected]
New tools in the treatment of motility disorders in children
Seminars in Pediatric Surgery (2009) 18, 274-277
New tools in the treatment of motility disorders in children Robert Carachi, MD, PhD, FRCS (Eng), FRCS (Glas), FEBPS,a John M. Currie, MBChB, FRCA,b Mairi Steven, BSc, MBChB, MRCSa From the aDepartment of Paediatric Surgery, Royal Hospital for Sick Children, Glasgow, United Kingdom; and the b Department of Anaesthesia, Royal Hospital for Sick Children, Glasgow, United Kingdom. KEYWORDS Gastrointestinal dysmotility; Celiac plexus block; Splanchnectomy
Gastrointestinal motility disorders can develop in neurologically impaired children and those with congenital malformations of the gut. It is characterized by moderate to severe abdominal pain, vomiting, and failure to thrive. Antral dysmotility after fundoplication and increased sympathetic over activity are 2 factors associated with this condition that make it difficult to treat. This paper proposes a management strategy using metoclopramide, celiac plexus blockade, and thoracic splanchnectomy. It reviews our experience with 11 patients. © 2009 Elsevier Inc. All rights reserved.
Background Gastrointestinal dysmotility remains a major problem in pediatric clinical practice, especially in the treatment of neurologically impaired children.1,2 Gastrointestinal dysmotility syndrome describes a group of disorders that involve failure of the normal peristalsis of the gastrointestinal tract.3 Pediatricians have long recognized that many children with cerebral palsy have a poor quality of life because of severe retching, vomiting, and inability to tolerate feeds.4 Despite many advances in the understanding of how the enteric nervous system develops, such as the role of the interstitial cell of Cajal pacemaker and the involvement of humoral factors,5-8 there remain a large number of children for which management strategies for dysmotility are severely lacking. Many of these children undergo laparoscopic fundoplication and gastrostomy insertion to overcome the gastroesophageal reflux (GOR) part of their Address reprint requests and correspondence: Robert Carachi, MD, PhD, FRCS (Eng), FRCS (Glas), FEBPS, Division of Developmental Medicine, Section of Surgical Paediatrics, University of Glasgow, The Royal Hospital for Sick Children, Dalnair Street, Yorkhill, Glasgow G3 8SJ, Scotland, UK. E-mail address: [email protected].
1055-8586/$ -see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2009.07.009
symptoms, or undergo laparotomy. Fundoplication in neurologically impaired children can result in the development or even progression of gastric dysrhythmia leading to retching, vomiting, and food intolerance.9,10 Some centers advocate esophagogastric dissociation as a last resort in children who have had a “failed fundoplication.”11 It is debatable, however, as to whether this is simply addressing GOR rather than antral or more widespread foregut dysmotility.
Current management Medical management offers a number of drugs that improve gastric emptying.12 The most popular of these is metoclopramide, but others include cisapride and erythromycin.13-15 Until recently, the only surgical option for children with severe dysmotility causing end-stage small intestinal failure was a small bowel transplant.16-18 The reported results in terms of mortality and long-term morbidity are not favorable. A recent report published in 2005 examining 12 smallbowel transplants in children with gastrointestinal dysmotility reported a survival rate of 66.7% at 1 year and 50% at 3 years.19
Carachi et al
New Tools in the Treatment of Motility Disorders in Children
Low dose metoclopramide max daily dose 500microg/kg PO/four divided doses If no improvement seen Celiac plexus block (CB) Posterior approach - 0.5% Bupivicaine Fluoroscopic guidance
275
per gastrointestinal motility and relaxation of the pyloric sphincter.21 It, therefore, modifies antral dysrhythmia. We would advocate starting patients on this as a first-line treatment. If no improvement is seen, then the child should be considered for a celiac plexus block. Low-dose metoclopramide is administered as a daily dose 500 micrograms per kilogram orally in four divided doses.
If improvement seen Thoracic Splanchnectomy
Figure 1 Three-step management protocol. (Color version of figure is available online.)
This figure is improving as illustrated in the paper on transplantation by Millar and coworkers, but the morbidity is still high and alternative strategies are more desirable.
Our approach Our approach recently has been threefold (Figure 1).
Basic science The splanchnic nerves arise from the lower eight thoracic sympathetic ganglia and give rise to a network of postganglionic fibers known as the celiac plexus. These sympathetic fibers are vasomotor and inhibitory to peristalsis and are known to carry sensory fibers to the abdominal viscera.20 It follows, therefore that interrupting this network not only interrupts nociceptive pathways but also affects motility (Figure 2). The vomiting or emetic reflex is a neural reflex that involves sensory and motor pathways of the vagus nerve. Its exact mechanisms are poorly understood but are thought to involve the area postrema and the vomiting center in the brain stem. More recently, it has become accepted that vagal afferents are involved in the changes seen in gut motor activity.21 The reflex can be stimulated by damage to these fibers or damage to gastric or bowel wall mucosa. A fundoplication wrap may also alter the morphology of the stomach itself.9 In children with disorders of the central nervous system, the extrinsic innervation to the foregut is thought to be abnormal and the vomiting center and area postrema may be dysfunctional.1 Antral dysrhythmia may also be a result of anoxic brain injury, and this may lead to an abnormal emetic reflex. These patients may well have more widespread dysfunction of intrinsic nerves leading to panenteric dysfunction and dysmotility.1
Celiac plexus block A celiac plexus block is a way of interrupting this network, and a study in adult practice has shown that this procedure reduced gastrointestinal dysfunction in neurosurgical ICU patients.22 The procedure is performed under general anesthetic by a lead pain consultant. It is performed under fluoroscopic guidance. Intravenous fluids are required preblock to reduce the risk of hypotension after the procedure. The needle is inserted just below the tip of the 12th rib and advanced until it reaches the side of the L1 vertebra (Figure 3A). The needle is withdrawn slightly and then redirected forwards until it is in the area of the celiac plexus, avoiding the aorta and inferior vena cava. Radioopaque dye is injected to confirm the correct placement of the needle (Figure 3B) and levobupivicaine injected. The average response and relief of symptoms lasts, in our experience, about 28 days but can be up to 6 weeks. Blocks can be repeated and may show and enhanced response. Complications include hypotension, intravascular injection, and retroperitoneal hematoma.
Metoclopramide Metoclopramide is a prokinetic and dopamine antagonist that increases sensitivity to acetylcholine resulting in increased up-
Figure 2
Anatomy of the celiac plexus and splanchnic nerves.
276
Seminars in Pediatric Surgery, Vol 18, No 4, November 2009
Figure 3
(A) Celiac plexus block technique. (B) Radio-opaque dye injected.
Thoracic splanchnectomy Thoracic splanchnectomy has been used in adult practice to treat pain in pancreatic cancer and chronic pancreatitis.23-26 Successful bilateral thoracoscopic splanchnectomy has been reported in two children with chronic intestinal pseudoobstruction.27 Bilateral thoracoscopic splanchnectomy was first described in 1994.28 The patient is placed under general anesthetic in the lateral decubitus position with the contralateral lung ventilated. A two-port technique is used using 5-mm ports placed in the sixth intercostal space in the anterior and midaxillary lines. Some authors advocate a three-port technique.29 Carbon dioxide is insufflated at 6-8 mm Hg. The greater and lesser splanchnic nerves are identified and isolated with the diathermy hook and divided. The patient is then turned and the same procedure performed on the opposite side. An intercostal drain is not routinely placed. It has been postulated that the effect on symptoms is due to a blockade of inhibitory sympathetic signals, leading to an increase in motility and reduction in water absorption.30 In our experience, patients have shown both immediate and permanent pain relief and improvement in feeding. This again supports the concept that the sympathetic nervous system and splanchnic nerves are involved in both pain pathways and the pathophysiology of gastrointestinal dysmotility syndrome.
Our experience We now have a series of 11 patients that we have managed with the above protocol since 2000 (7 boys and 4 girls) who had not responded to conventional treatment. Median age is 13 years (3-21). Symptoms varied from constant retching and vomiting to severe abdominal pain and feeding diffi-
culties. Seven had severe neurological abnormalities, 6 had a fundoplication, and 3 had a gastrostomy. Four patients improved with metoclopramide alone. The 7 other patients underwent celiac plexus block. The median number of blocks was 3 (1-27). No complications were encountered. Five patients underwent thoracic splanchnectomy by minimal invasive surgery. In 1 patient, this was performed thoracoscopically, and the patient had to have an open procedure subsequently which involved a laparotomy and celiac node removal. All 11 patients had relief of their symptoms. Follow-up ranged from 4 months to 8 years.
Future developments In addition to the ongoing research into the development of the enteric nervous system, there are also exciting new modalities for investigating foregut motility, namely highresolution manometry.31 This new tool allows unprecedented detailed information on gastric emptying, duodenal pressures, and bolus transit. This may be of use both in further research and in helping identify suitable patients.
Conclusion In conclusion, we believe a combination of low-dose metoclopramide, celiac plexus block, and thoracic splanchnectomy are effective tools in the management of children with gastrointestinal motility disorder. High-resolution manometry may prove useful in identifying suitable patients. Further research is required to provide the scientific proof needed to further advocate these procedures as an alternative minimally invasive surgical option for these children. An animal model to study the effect of cerebral palsy on motility disorders is being studied.32
Carachi et al
New Tools in the Treatment of Motility Disorders in Children
References 1. Ravelli AM, Milla PJ. Vomiting and gastroesophageal motor activity in children with disorders of the central nervous system. J Pediatr Gastroenterol Nutr 1998;26:56-63. 2. Staiano A, Cucchiara S, Del Giudice E, et al. Disorders of oesophageal motility in children with psychomotor retardation and gastrooesophageal reflux. Eur J Pediatr 1991;150:638-41. 3. Smith VV. Chronic intestinal pseudo-obstruction: The pathologist’s perspective. J Pediatr Gastroenterol Nutr 2001;32:S23-4. 4. Reyes AL, Cash AJ, Green SH, et al. Gastrooesophageal reflux in children with cerebral palsy. Child Care Health Dev 2009;19:10918. 5. Burns AJ, Pachnis V. Development of the enteric nervous system: Bringing together cells, signals and genes. Neurogastroenterol Motil 2009;21:100-2. 6. Young HM. Functional development of the enteric nervous system. From migration to motility. Neurogastroenterol Motil 2008;20:20-31 (suppl 1). 7. Bates MD. Development of the enteric nervous system. Clin Perinatol 2002;29:97-114. 8. Sanders KM, Ordog T, Ward SM. Physiology and pathophysiology of the interstitial cells of Cajal: From bench to bedside. Am J Physiol Gastrointest Liver Physiol 2002;282:G747-56. 9. Richards CA, Andres PLR, Spitz L, et al. Nissen fundoplication may induce gastric myoelectrical disturbance in children. J Pediatr Surg 1998;33:1801-5. 10. Goyal A, Khalil B, Choo K, et al. Esophagogastric dissociation in the neurologically impaired: An alternative to fundoplication? J Pediatr Surg 2005;40:915-19. 11. McCallum RW. Clinical pharmacology forum: Motility agents and the gastrointestinal tract. Am J Med Sci 1996;312:19-26. 12. McCallum RW. Cisapride: A new class of prokinetic agent. The ACG Committee on FDA-related matters; American College of Gastroenterology. Am J Gastroenterol 1991;86:135-49. 13. Chen JD, Lin ZY, Edmunds MC III, et al. Effects of octreotide and erythromycin on gastric myoelectrical and motor activities in patients with gastroparesis. Dig Dis Sci 1998;43:80-9. 14. Otterson MF, Sarna SK. Gastrointestinal motor effects of erythromycin. Am J Physiol 1990;259:G355-63. 15. Bond GJ, Reyes JD. Intestinal transplantation for total/near-total aganglionosis and intestinal pseudo-obstruction. Semin Pediatr Surg 2004; 13:286-92. 16. Raofia V, Beattya E, Testaa G, et al. Combined living-related segmental liver and bowel transplantation for megacystis-microcolon-intestinal hypoperistalsis syndrome. J Pediatr Surg 2008;43:e9-11.
277
17. Mittal N, Loinez C, Kato T, et al. Multivisceral transplantation for pediatric intestinal pseudo-obstruction: Single center’s experience of 16 cases. The VIII Internation Small Bowel Symposia (Abstr), 2003. 18. Loinaz C, Rodríguez MM, Kato T, et al. Intestinal and multivisceral transplantation in children with severe gastrointestinal dysmotility. J Pediatr Surg 2005;40:1598-604. 19. McMinn RMH. Lasts Anatomy Regional and Applied (ed 9). London: Churchill Livingstone, 1994. 20. Andrews PL, Hawthorn J. The neurophysiology of vomiting. Baillieres Clin Gastroenterol 1998;2:141-68. 21. Pandolfino JE, Howden CW, Kahrilas PJ. Motility-modifying agents and management of disorders of gastrointestinal motility. Gastroenterology 2000;118:S32-47 (suppl 1). 22. Weinstable C, Porges P, Plainer B, et al. Coeliac plexus block with bupivacaine reduces intestinal dysfunction in neurosurgical ICU patients. Anaesthesia 1993;48:162-4. 23. Lebovits AH, Lefkowitz M. Pain management of pancreatic carcinoma: A review. Pain 1989;36:1-11. 24. Ihse I, Borch K, Larsson J. Chronic pancreatitis: Results of operations for relief of pain. World J Surg 1990;14:53-8. 25. Baghdadi S, Abbas MH, Albouz F, et al. Systematic review of the role of thoracoscopic splanchnicectomy in palliating the pain of patients with chronic pancreatitis. Surg Endosc 2008;22:580-8. 26. Buscher HC, Jansen JB, van Dongen R, et al. Long-term results of bilateral thoracoscopic splanchnicectomy in patients with chronic pancreatitis. Br J Surg 2002;89:158-62. 27. Khelif K, Scaillon M, Govaerts MJM, et al. Bilateral thoracoscopic splanchnicectomy in chronic intestinal pseudo-obstruction: Report of two paediatric cases. Gut 2006;55:293-4. 28. Cuschieri A, Shimi SM, Crosthwaite G, et al. Bilateral endoscopic splanchnicectomy through posterior thoracoscopic approach. J R Coll Surg Edinb 1994;39:44-7. 29. Kang CM, Lee HY, Yang HJ, et al. Bbilateral thoracoscopic splanchnicectomy with sympathectomy for managing abdominal pain in cancer patients. Am J Surg 2007;194:23-9. 30. Mercadente S. Octreotide in the treatment of diarrhea induced by celiac plexus block. Pain 1995;61:345-6. 31. Andrews JM, O’Donovan DG, Hebbard GS, et al. Human duodenal phase iii migrating motor complex activity is predominantly antegrade, as revealed by high-resolution manometry and colour pressure plots. Neurogastroenterol Motil 2002;14:331-8. 32. Chen A, Dimambro N, Clowry GJ. A comparison of behavioural and histological outcomes of periventricular injection of ibotenic acid in neonatal rats at postnatal days 5 and 7. Brain Res 2008; 1201:187-95.
New tools in the treatment of motility disorders in children Robert Carachi, MD, PhD, FRCS (Eng), FRCS (Glas), FEBPS,a John M. Currie, MBChB, FRCA,b Mairi Steven, BSc, MBChB, MRCSa From the aDepartment of Paediatric Surgery, Royal Hospital for Sick Children, Glasgow, United Kingdom; and the b Department of Anaesthesia, Royal Hospital for Sick Children, Glasgow, United Kingdom. KEYWORDS Gastrointestinal dysmotility; Celiac plexus block; Splanchnectomy
Gastrointestinal motility disorders can develop in neurologically impaired children and those with congenital malformations of the gut. It is characterized by moderate to severe abdominal pain, vomiting, and failure to thrive. Antral dysmotility after fundoplication and increased sympathetic over activity are 2 factors associated with this condition that make it difficult to treat. This paper proposes a management strategy using metoclopramide, celiac plexus blockade, and thoracic splanchnectomy. It reviews our experience with 11 patients. © 2009 Elsevier Inc. All rights reserved.
Background Gastrointestinal dysmotility remains a major problem in pediatric clinical practice, especially in the treatment of neurologically impaired children.1,2 Gastrointestinal dysmotility syndrome describes a group of disorders that involve failure of the normal peristalsis of the gastrointestinal tract.3 Pediatricians have long recognized that many children with cerebral palsy have a poor quality of life because of severe retching, vomiting, and inability to tolerate feeds.4 Despite many advances in the understanding of how the enteric nervous system develops, such as the role of the interstitial cell of Cajal pacemaker and the involvement of humoral factors,5-8 there remain a large number of children for which management strategies for dysmotility are severely lacking. Many of these children undergo laparoscopic fundoplication and gastrostomy insertion to overcome the gastroesophageal reflux (GOR) part of their Address reprint requests and correspondence: Robert Carachi, MD, PhD, FRCS (Eng), FRCS (Glas), FEBPS, Division of Developmental Medicine, Section of Surgical Paediatrics, University of Glasgow, The Royal Hospital for Sick Children, Dalnair Street, Yorkhill, Glasgow G3 8SJ, Scotland, UK. E-mail address: [email protected].
1055-8586/$ -see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2009.07.009
symptoms, or undergo laparotomy. Fundoplication in neurologically impaired children can result in the development or even progression of gastric dysrhythmia leading to retching, vomiting, and food intolerance.9,10 Some centers advocate esophagogastric dissociation as a last resort in children who have had a “failed fundoplication.”11 It is debatable, however, as to whether this is simply addressing GOR rather than antral or more widespread foregut dysmotility.
Current management Medical management offers a number of drugs that improve gastric emptying.12 The most popular of these is metoclopramide, but others include cisapride and erythromycin.13-15 Until recently, the only surgical option for children with severe dysmotility causing end-stage small intestinal failure was a small bowel transplant.16-18 The reported results in terms of mortality and long-term morbidity are not favorable. A recent report published in 2005 examining 12 smallbowel transplants in children with gastrointestinal dysmotility reported a survival rate of 66.7% at 1 year and 50% at 3 years.19
Carachi et al
New Tools in the Treatment of Motility Disorders in Children
Low dose metoclopramide max daily dose 500microg/kg PO/four divided doses If no improvement seen Celiac plexus block (CB) Posterior approach - 0.5% Bupivicaine Fluoroscopic guidance
275
per gastrointestinal motility and relaxation of the pyloric sphincter.21 It, therefore, modifies antral dysrhythmia. We would advocate starting patients on this as a first-line treatment. If no improvement is seen, then the child should be considered for a celiac plexus block. Low-dose metoclopramide is administered as a daily dose 500 micrograms per kilogram orally in four divided doses.
If improvement seen Thoracic Splanchnectomy
Figure 1 Three-step management protocol. (Color version of figure is available online.)
This figure is improving as illustrated in the paper on transplantation by Millar and coworkers, but the morbidity is still high and alternative strategies are more desirable.
Our approach Our approach recently has been threefold (Figure 1).
Basic science The splanchnic nerves arise from the lower eight thoracic sympathetic ganglia and give rise to a network of postganglionic fibers known as the celiac plexus. These sympathetic fibers are vasomotor and inhibitory to peristalsis and are known to carry sensory fibers to the abdominal viscera.20 It follows, therefore that interrupting this network not only interrupts nociceptive pathways but also affects motility (Figure 2). The vomiting or emetic reflex is a neural reflex that involves sensory and motor pathways of the vagus nerve. Its exact mechanisms are poorly understood but are thought to involve the area postrema and the vomiting center in the brain stem. More recently, it has become accepted that vagal afferents are involved in the changes seen in gut motor activity.21 The reflex can be stimulated by damage to these fibers or damage to gastric or bowel wall mucosa. A fundoplication wrap may also alter the morphology of the stomach itself.9 In children with disorders of the central nervous system, the extrinsic innervation to the foregut is thought to be abnormal and the vomiting center and area postrema may be dysfunctional.1 Antral dysrhythmia may also be a result of anoxic brain injury, and this may lead to an abnormal emetic reflex. These patients may well have more widespread dysfunction of intrinsic nerves leading to panenteric dysfunction and dysmotility.1
Celiac plexus block A celiac plexus block is a way of interrupting this network, and a study in adult practice has shown that this procedure reduced gastrointestinal dysfunction in neurosurgical ICU patients.22 The procedure is performed under general anesthetic by a lead pain consultant. It is performed under fluoroscopic guidance. Intravenous fluids are required preblock to reduce the risk of hypotension after the procedure. The needle is inserted just below the tip of the 12th rib and advanced until it reaches the side of the L1 vertebra (Figure 3A). The needle is withdrawn slightly and then redirected forwards until it is in the area of the celiac plexus, avoiding the aorta and inferior vena cava. Radioopaque dye is injected to confirm the correct placement of the needle (Figure 3B) and levobupivicaine injected. The average response and relief of symptoms lasts, in our experience, about 28 days but can be up to 6 weeks. Blocks can be repeated and may show and enhanced response. Complications include hypotension, intravascular injection, and retroperitoneal hematoma.
Metoclopramide Metoclopramide is a prokinetic and dopamine antagonist that increases sensitivity to acetylcholine resulting in increased up-
Figure 2
Anatomy of the celiac plexus and splanchnic nerves.
276
Seminars in Pediatric Surgery, Vol 18, No 4, November 2009
Figure 3
(A) Celiac plexus block technique. (B) Radio-opaque dye injected.
Thoracic splanchnectomy Thoracic splanchnectomy has been used in adult practice to treat pain in pancreatic cancer and chronic pancreatitis.23-26 Successful bilateral thoracoscopic splanchnectomy has been reported in two children with chronic intestinal pseudoobstruction.27 Bilateral thoracoscopic splanchnectomy was first described in 1994.28 The patient is placed under general anesthetic in the lateral decubitus position with the contralateral lung ventilated. A two-port technique is used using 5-mm ports placed in the sixth intercostal space in the anterior and midaxillary lines. Some authors advocate a three-port technique.29 Carbon dioxide is insufflated at 6-8 mm Hg. The greater and lesser splanchnic nerves are identified and isolated with the diathermy hook and divided. The patient is then turned and the same procedure performed on the opposite side. An intercostal drain is not routinely placed. It has been postulated that the effect on symptoms is due to a blockade of inhibitory sympathetic signals, leading to an increase in motility and reduction in water absorption.30 In our experience, patients have shown both immediate and permanent pain relief and improvement in feeding. This again supports the concept that the sympathetic nervous system and splanchnic nerves are involved in both pain pathways and the pathophysiology of gastrointestinal dysmotility syndrome.
Our experience We now have a series of 11 patients that we have managed with the above protocol since 2000 (7 boys and 4 girls) who had not responded to conventional treatment. Median age is 13 years (3-21). Symptoms varied from constant retching and vomiting to severe abdominal pain and feeding diffi-
culties. Seven had severe neurological abnormalities, 6 had a fundoplication, and 3 had a gastrostomy. Four patients improved with metoclopramide alone. The 7 other patients underwent celiac plexus block. The median number of blocks was 3 (1-27). No complications were encountered. Five patients underwent thoracic splanchnectomy by minimal invasive surgery. In 1 patient, this was performed thoracoscopically, and the patient had to have an open procedure subsequently which involved a laparotomy and celiac node removal. All 11 patients had relief of their symptoms. Follow-up ranged from 4 months to 8 years.
Future developments In addition to the ongoing research into the development of the enteric nervous system, there are also exciting new modalities for investigating foregut motility, namely highresolution manometry.31 This new tool allows unprecedented detailed information on gastric emptying, duodenal pressures, and bolus transit. This may be of use both in further research and in helping identify suitable patients.
Conclusion In conclusion, we believe a combination of low-dose metoclopramide, celiac plexus block, and thoracic splanchnectomy are effective tools in the management of children with gastrointestinal motility disorder. High-resolution manometry may prove useful in identifying suitable patients. Further research is required to provide the scientific proof needed to further advocate these procedures as an alternative minimally invasive surgical option for these children. An animal model to study the effect of cerebral palsy on motility disorders is being studied.32
Carachi et al
New Tools in the Treatment of Motility Disorders in Children
References 1. Ravelli AM, Milla PJ. Vomiting and gastroesophageal motor activity in children with disorders of the central nervous system. J Pediatr Gastroenterol Nutr 1998;26:56-63. 2. Staiano A, Cucchiara S, Del Giudice E, et al. Disorders of oesophageal motility in children with psychomotor retardation and gastrooesophageal reflux. Eur J Pediatr 1991;150:638-41. 3. Smith VV. Chronic intestinal pseudo-obstruction: The pathologist’s perspective. J Pediatr Gastroenterol Nutr 2001;32:S23-4. 4. Reyes AL, Cash AJ, Green SH, et al. Gastrooesophageal reflux in children with cerebral palsy. Child Care Health Dev 2009;19:10918. 5. Burns AJ, Pachnis V. Development of the enteric nervous system: Bringing together cells, signals and genes. Neurogastroenterol Motil 2009;21:100-2. 6. Young HM. Functional development of the enteric nervous system. From migration to motility. Neurogastroenterol Motil 2008;20:20-31 (suppl 1). 7. Bates MD. Development of the enteric nervous system. Clin Perinatol 2002;29:97-114. 8. Sanders KM, Ordog T, Ward SM. Physiology and pathophysiology of the interstitial cells of Cajal: From bench to bedside. Am J Physiol Gastrointest Liver Physiol 2002;282:G747-56. 9. Richards CA, Andres PLR, Spitz L, et al. Nissen fundoplication may induce gastric myoelectrical disturbance in children. J Pediatr Surg 1998;33:1801-5. 10. Goyal A, Khalil B, Choo K, et al. Esophagogastric dissociation in the neurologically impaired: An alternative to fundoplication? J Pediatr Surg 2005;40:915-19. 11. McCallum RW. Clinical pharmacology forum: Motility agents and the gastrointestinal tract. Am J Med Sci 1996;312:19-26. 12. McCallum RW. Cisapride: A new class of prokinetic agent. The ACG Committee on FDA-related matters; American College of Gastroenterology. Am J Gastroenterol 1991;86:135-49. 13. Chen JD, Lin ZY, Edmunds MC III, et al. Effects of octreotide and erythromycin on gastric myoelectrical and motor activities in patients with gastroparesis. Dig Dis Sci 1998;43:80-9. 14. Otterson MF, Sarna SK. Gastrointestinal motor effects of erythromycin. Am J Physiol 1990;259:G355-63. 15. Bond GJ, Reyes JD. Intestinal transplantation for total/near-total aganglionosis and intestinal pseudo-obstruction. Semin Pediatr Surg 2004; 13:286-92. 16. Raofia V, Beattya E, Testaa G, et al. Combined living-related segmental liver and bowel transplantation for megacystis-microcolon-intestinal hypoperistalsis syndrome. J Pediatr Surg 2008;43:e9-11.
277
17. Mittal N, Loinez C, Kato T, et al. Multivisceral transplantation for pediatric intestinal pseudo-obstruction: Single center’s experience of 16 cases. The VIII Internation Small Bowel Symposia (Abstr), 2003. 18. Loinaz C, Rodríguez MM, Kato T, et al. Intestinal and multivisceral transplantation in children with severe gastrointestinal dysmotility. J Pediatr Surg 2005;40:1598-604. 19. McMinn RMH. Lasts Anatomy Regional and Applied (ed 9). London: Churchill Livingstone, 1994. 20. Andrews PL, Hawthorn J. The neurophysiology of vomiting. Baillieres Clin Gastroenterol 1998;2:141-68. 21. Pandolfino JE, Howden CW, Kahrilas PJ. Motility-modifying agents and management of disorders of gastrointestinal motility. Gastroenterology 2000;118:S32-47 (suppl 1). 22. Weinstable C, Porges P, Plainer B, et al. Coeliac plexus block with bupivacaine reduces intestinal dysfunction in neurosurgical ICU patients. Anaesthesia 1993;48:162-4. 23. Lebovits AH, Lefkowitz M. Pain management of pancreatic carcinoma: A review. Pain 1989;36:1-11. 24. Ihse I, Borch K, Larsson J. Chronic pancreatitis: Results of operations for relief of pain. World J Surg 1990;14:53-8. 25. Baghdadi S, Abbas MH, Albouz F, et al. Systematic review of the role of thoracoscopic splanchnicectomy in palliating the pain of patients with chronic pancreatitis. Surg Endosc 2008;22:580-8. 26. Buscher HC, Jansen JB, van Dongen R, et al. Long-term results of bilateral thoracoscopic splanchnicectomy in patients with chronic pancreatitis. Br J Surg 2002;89:158-62. 27. Khelif K, Scaillon M, Govaerts MJM, et al. Bilateral thoracoscopic splanchnicectomy in chronic intestinal pseudo-obstruction: Report of two paediatric cases. Gut 2006;55:293-4. 28. Cuschieri A, Shimi SM, Crosthwaite G, et al. Bilateral endoscopic splanchnicectomy through posterior thoracoscopic approach. J R Coll Surg Edinb 1994;39:44-7. 29. Kang CM, Lee HY, Yang HJ, et al. Bbilateral thoracoscopic splanchnicectomy with sympathectomy for managing abdominal pain in cancer patients. Am J Surg 2007;194:23-9. 30. Mercadente S. Octreotide in the treatment of diarrhea induced by celiac plexus block. Pain 1995;61:345-6. 31. Andrews JM, O’Donovan DG, Hebbard GS, et al. Human duodenal phase iii migrating motor complex activity is predominantly antegrade, as revealed by high-resolution manometry and colour pressure plots. Neurogastroenterol Motil 2002;14:331-8. 32. Chen A, Dimambro N, Clowry GJ. A comparison of behavioural and histological outcomes of periventricular injection of ibotenic acid in neonatal rats at postnatal days 5 and 7. Brain Res 2008; 1201:187-95.