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Localized isolated hypoganglionosis in an infant
Journal of Pediatric Surgery Case Reports 28 (2018) 48–50
Contents lists available at ScienceDirect
Journal of Pediatric Surgery Case Reports journal homepage: www.elsevier.com/locate/epsc
Localized isolated hypoganglionosis in an infant a,∗
a
a
MARK b
b
Taizo Furukawa , Yuki Takeuchi , Tomoko Tanaka , Koichiro Yoshimaru , Tomoaki Taguchi , Tatsuro Tajiria a b
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Japan Department of Pediatric Surgery, Graduate School of Medical Science, Kyushu University, Japan
1. Introduction Isolated hypoganglionosis (IHG) is rare and has been classified as a hypogenetic type of intestinal dysganglionoses [1]. Although the clinical features of IHG are similar to those of Hirschsprung's disease (HD), IHG is characterized by scarce ganglion cells and plexuses in the intestinal wall. Although many cases with IHG reported in Europe are of the localized type [2,3], almost all IHG cases reported in Japan are of the generalized type and require jejunostomy or ileostomy during the neonatal period [4–6]. These divergent views were highlighted in a report from the fourth International Symposium on Hirschsprung disease and related neurocristopathies, held in 2004 [7]. Whether or not the localized and generalized types of IHG are the same entity is unclear. We herein report a female infant with localized IHG who achieved self-defecation after transanal endorectal pull-through (TAEPT).
colon. TAEPT was therefore performed. Histopathologically, Hu C/D-positive ganglion cells were sparsely found in the submucosa of the anal-side stump, which was located immediately proximal to the dentate line of the anal canal (Fig. 2A). These ganglion cells were small and immature. In addition, CD56-positive Meissner plexuses were few and small in number in the same area (Fig. 2B). The ganglion cells and the size of the Auerbach plexus gradually increased as the specimens approached the oral-side stump (Fig. 2C–F). These pathological findings were compatible with
2. Case report The patient was a two-day-old girl who had abdominal distension and bilious vomiting. Contrast enema revealed no narrow segment of the rectum at two days of age. Glycerin enema showed a good response, but she had no self-defecation. Although anorectal manometry showed no anorectal reflex, contrast enema revealed no narrow segment at two months of age. A rectal mucosal biopsy at two months of age revealed no ganglion cells in the submucosa. Acetylchoinesterase (AChE) staining following the Karnovsky and Roots method [8] showed that there was no proliferation of AChE-positive nerve fibers in the mucosa or submucosa at two months of age. Contrast enema at four months of age revealed a narrow segment in the recto-sigmoid region (Fig. 1). However, a rectal mucosal biopsy still showed no ganglion cells and no proliferation of AChE-positive nerve fibers at five months of age (Table 1). She was suspected of having HD or its allied disorder. She underwent laparoscopic-assisted TAEPT at six months of age. The operative findings showed a caliber change in the sigmoid colon. A full-thickness biopsy for frozen sectioning was taken in the proximal portion of the transitional zone in the sigmoid colon. The intraoperative frozen section showed ganglion cells in the sigmoid
∗
Fig. 1. Contrast enema. Narrow segment in the recto-sigmoid region (arrow head).
Corresponding author. E-mail address: [email protected] (T. Furukawa).
http://dx.doi.org/10.1016/j.epsc.2017.09.036 Received 29 September 2017; Accepted 30 September 2017 Available online 03 October 2017 2213-5766/ © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Journal of Pediatric Surgery Case Reports 28 (2018) 48–50
T. Furukawa et al.
localized-type IHG. The postoperative course was excellent. Postoperative contrast enema showed no narrow segment in the residual colon (Fig. 3). She achieved self-defecation once or twice a day with no medication for two years postoperatively.
Table 1 Preoperative examination findings. Age 2 days Contrast enema Caliber change not detected Manometry Anorectal reflex Rectal mucosal biopsy Ganglion cells AChE-positive nerve fibers
2 months
4 months
not detected
recto-sigmoid
absence
absence
not detected not increased
not detected not increased
5 months
3. Discussion Hypoganglionosis is rare entity among intestinal innervation disorders. Tiffin et al. [9] first mentioned hypoganglionosis without aganglionosis. Meier-Ruge et al. [2] reported 7 children with IHG between 6 and 11 years of age showing megacolon, meteorism, and temporary subileus symptoms. They concluded that the most important findings of morphometric investigations of hypoganglionosis are a decrease in the plexus area and nerve cell number in the myenteric plexus
not detected not increased
AChE, acetylcholinesterase.
Fig. 2. Histological findings of immunohistochemical staining using Hu C/D and CD 56. A. Ganglion cells were sparsely found in the dentate line of the anal canal (arrow head). B. Meissner plexuses were few in number and small in size in the dentate line of the anal canal (arrow head). C. The ganglion cells were still few in number in the center portion of the resected intestine (arrow head). D. Auerbach plexuses were still few in number and small in size in the center portion of the resected intestine (arrow head). E. The ganglion cells were few in number but gradually increased in the oral-side stump (arrow head). F. Auerbach plexuses were small in size but gradually increased in the oral-side stump (arrow head).
49
Journal of Pediatric Surgery Case Reports 28 (2018) 48–50
T. Furukawa et al.
extends to the total intestine [4–6,16]. Jejunostomy or ileostomy are often created as the initial operation because most patients with generalized-type IHG show a caliber change at the small intestine. However, ileostomy often causes malfunction of the fecal output and requires stoma creation with a shorter distance from the ligament of Treitz [17]. Watanabe et al. suggested that patients with IHG undergo jejunostomy at less than 50 cm from the ligament of Treitz during the neonatal period to manage IHG successfully [6]. The most common type of IHG differs between Europe and Japan. However, there have been no reports regarding such regional differences in the type of IHG. HD cases are divided into several types according to the length of the aganglionic segment. Most HD cases are short-segment aganlionosis, and extensive or total intestinal aganglionosis is rare. In contrast, the localization of IHG is extremely long in most IHG cases in Japan. Whether or not the localized type, such as colonic hypoganglionosis, and the generalized type, which requires upper jejunostomy, are the same entity is unclear at present. Further investigations are needed to elucidate these controversies regarding types of IHG. Conflict of interest The authors have no conflicts of interest to disclose. Acknowledgement The authors thank Mr. Brian Quinn for reviewing the English used in this manuscript (Japan Medical Communication, Inc.). Fig. 3. Postoperative contrast enema. No narrow segment in the residual colon.
References and an increase in the ganglion distances. However, according to a report from the fourth International Symposium on Hirschsprung disease and related neurocristopathies, held in 2004, there was broad agreement regarding the difficulty of diagnosing hypoganglionosis [7]. Some doctors do not think that hypoganglionosis really exists, so hypoganglionosis has not yet been established as an isolated entity worldwide. Histologically, in patients with hypoganglionosis, there are extremely few ganglion cells in the neonatal period, and their size is small [10]. The size of the Auerbach plexus is also small. The diameter of the nucleus of ganglion cells increases over time, but the numbers of these cells do not increase at all [10]. In immunohistochemical staining, Hu C/D is a reliable pan-neuronal marker for enteric nervous system (ENS) neurons because Hu immunoreactivity is strong in both the nuclei and cytoplasm of permanently labeled myenteric neurons [11]. Immunohistochemical staining for Hu C/D has proven useful in identifying a decrease in the number of ganglion cells in congenital isolated hypoganglionosis [12]. CD56 is particularly useful in the diagnosis of hypoganglionosis because it is a general neuronal marker staining all nerves [12,13]. In this case, Hu C/D-positive ganglion cells were sparsely found in the anal-side stump, which was located immediately proximal to the dentate line of the anal canal. There were also a few small CD56-positive Meissner plexuses in the same area. These findings are compatible with IHG. In addition, the number of ganglion cells and the size of the Auerbach plexus gradually increased as the specimens approached the oral-side stump. Although biopsies were not taken from the residual intestine, we believe that the number of ganglion cells in the residual colon is almost normal, as she achieved self-defecation after surgery with no medication. Postoperative contrast enema showed no narrow segment in the residual colon. The postoperative course of this case correlates with that of localized-type IHG. Although most cases with IHG are localized-type, such as colonic hypoganglinosis in Europe [10], the only such cases in Japan were reported by Yamataka et al. [14] and Munakawa et al. [15] as colonic hypoganglionosis in the 1990s. Since then, almost all IHG cases reported in Japan have been the generalized type, in which localization
[1] Schärli AF. Standardization of terminology of intestinal innervation disorders. Pediatr Surg Int 1995;10:440. [2] Meier-Ruge WA, Brunner LA, Engert J, Heminghaus M, Holschneider AM, Jordan P, et al. A correlative morphometric and clinical investigation of hypoganglionosis of the colon in children. Eur J Pediatr Surg 1999;9:67–74. [3] Dingemann J, Puri P. Isolated hypoganglionosis: systematic review of a rare intestinal innervation defect. Pediatr Surg Int 2010;26:1111–5. [4] Kobayashi H, Yamataka A, Lane GJ, Miyano T. Pathophysiology of hypoganglionosis. J Pediatr Gastroenterol Nutr 2002;34:231–5. [5] Kubota A, Yamauchi K, Yonekura T, Kosumi T, Oyanagi H, Mushiake S, et al. Clinicopathologic relationship of hypoganglionosis. J Pediatr Surg 2001;36:898–900. [6] Watanabe Y, Sumida W, Takasu H, Oshima K, Kanamori Y, Uchida K, et al. Early jejunostomy creation in cases of isolated hypoganglionosis: verification of our own experience based on a national survey. Surg Today 2015;45:1509–12. [7] Martucciello G, Prato AP, Puri P, Holschneider AM, Meier-Ruge WA, Jasonni V, et al. Controversies concerning diagnostic guidelines for anomalies of the enteric nervous system: a report from the fourth International Symposium on Hirschsprung's disease and related neurocristopathies. J Pediatr Surg 2005;40:1527–31. [8] Karnovsky MJ, Roots L. A "direct-colouring" thiocholine method of cholinesterase. J Histochem Cytochem 1964;12:219–21. [9] Tiffin ME, Chandler LR, Faber HK. Localized absence of the ganglion cell of myenteric plexus in congenital megacolon. Am J Dis Child 1940;59:1071–82. [10] Taguchi T, Masumoto K, Ieiri S, Nakatsuji T, Akiyoshi J. New classification of hypoganglionosis: congenital and acquired hypoganglionosis. J Pediatr Surg 2006;41:2046–51. [11] Phillips RJ, Hargrave SL, Rhodes BS, Zopf DA, Powley TL. Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers. J Neurosci Methods 2004;133:99–107. [12] Yoshimaru K, Taguchi T, Obata S, Takemoto J, Takahashi Y, Iwanaka T, et al. Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological diagnosis of congenital and acquired isolated hypoganglionosis. Virchows Arch 2017;470:679–85. [13] Nogueira A, Campos M, Soares-Oliveira M, Estevão-Costa J, Silva P, Carneiro F, et al. Histochemical and immunohistochemical study of the intrinsic innervation in colonic dysganglionosis. Pediatr Surg Int 2001;17:144–51. [14] Munakata K, Okabe I, Morita K. Hypoganglionosis. Pediatr Surg Int 1992;7:8–11. [15] Yamataka A, Fujiwara T, Nishiye H, Sunagawa M, Miyano T. Localization of intestinal pacemaker cells and synapses in the muscle layers of a patient with colonic hypoganglionosis. J Pediatr Surg 1996;31:584–7. [16] Watanabe Y, Kanamori Y, Uchida K, Taguchi T. Isolated hypoganglionosis: results of a nationwide survey in Japan. Pediatr Surg Int 2013;29:1127–30. [17] Watanabe Y, Takasu H, Sumida W. A preliminary report on the significance of excessively long segment congenital hypoganglionosis management during early infancy. J Pediatr Surg 2011;46:1572–7.
50
Contents lists available at ScienceDirect
Journal of Pediatric Surgery Case Reports journal homepage: www.elsevier.com/locate/epsc
Localized isolated hypoganglionosis in an infant a,∗
a
a
MARK b
b
Taizo Furukawa , Yuki Takeuchi , Tomoko Tanaka , Koichiro Yoshimaru , Tomoaki Taguchi , Tatsuro Tajiria a b
Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, Japan Department of Pediatric Surgery, Graduate School of Medical Science, Kyushu University, Japan
1. Introduction Isolated hypoganglionosis (IHG) is rare and has been classified as a hypogenetic type of intestinal dysganglionoses [1]. Although the clinical features of IHG are similar to those of Hirschsprung's disease (HD), IHG is characterized by scarce ganglion cells and plexuses in the intestinal wall. Although many cases with IHG reported in Europe are of the localized type [2,3], almost all IHG cases reported in Japan are of the generalized type and require jejunostomy or ileostomy during the neonatal period [4–6]. These divergent views were highlighted in a report from the fourth International Symposium on Hirschsprung disease and related neurocristopathies, held in 2004 [7]. Whether or not the localized and generalized types of IHG are the same entity is unclear. We herein report a female infant with localized IHG who achieved self-defecation after transanal endorectal pull-through (TAEPT).
colon. TAEPT was therefore performed. Histopathologically, Hu C/D-positive ganglion cells were sparsely found in the submucosa of the anal-side stump, which was located immediately proximal to the dentate line of the anal canal (Fig. 2A). These ganglion cells were small and immature. In addition, CD56-positive Meissner plexuses were few and small in number in the same area (Fig. 2B). The ganglion cells and the size of the Auerbach plexus gradually increased as the specimens approached the oral-side stump (Fig. 2C–F). These pathological findings were compatible with
2. Case report The patient was a two-day-old girl who had abdominal distension and bilious vomiting. Contrast enema revealed no narrow segment of the rectum at two days of age. Glycerin enema showed a good response, but she had no self-defecation. Although anorectal manometry showed no anorectal reflex, contrast enema revealed no narrow segment at two months of age. A rectal mucosal biopsy at two months of age revealed no ganglion cells in the submucosa. Acetylchoinesterase (AChE) staining following the Karnovsky and Roots method [8] showed that there was no proliferation of AChE-positive nerve fibers in the mucosa or submucosa at two months of age. Contrast enema at four months of age revealed a narrow segment in the recto-sigmoid region (Fig. 1). However, a rectal mucosal biopsy still showed no ganglion cells and no proliferation of AChE-positive nerve fibers at five months of age (Table 1). She was suspected of having HD or its allied disorder. She underwent laparoscopic-assisted TAEPT at six months of age. The operative findings showed a caliber change in the sigmoid colon. A full-thickness biopsy for frozen sectioning was taken in the proximal portion of the transitional zone in the sigmoid colon. The intraoperative frozen section showed ganglion cells in the sigmoid
∗
Fig. 1. Contrast enema. Narrow segment in the recto-sigmoid region (arrow head).
Corresponding author. E-mail address: [email protected] (T. Furukawa).
http://dx.doi.org/10.1016/j.epsc.2017.09.036 Received 29 September 2017; Accepted 30 September 2017 Available online 03 October 2017 2213-5766/ © 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
Journal of Pediatric Surgery Case Reports 28 (2018) 48–50
T. Furukawa et al.
localized-type IHG. The postoperative course was excellent. Postoperative contrast enema showed no narrow segment in the residual colon (Fig. 3). She achieved self-defecation once or twice a day with no medication for two years postoperatively.
Table 1 Preoperative examination findings. Age 2 days Contrast enema Caliber change not detected Manometry Anorectal reflex Rectal mucosal biopsy Ganglion cells AChE-positive nerve fibers
2 months
4 months
not detected
recto-sigmoid
absence
absence
not detected not increased
not detected not increased
5 months
3. Discussion Hypoganglionosis is rare entity among intestinal innervation disorders. Tiffin et al. [9] first mentioned hypoganglionosis without aganglionosis. Meier-Ruge et al. [2] reported 7 children with IHG between 6 and 11 years of age showing megacolon, meteorism, and temporary subileus symptoms. They concluded that the most important findings of morphometric investigations of hypoganglionosis are a decrease in the plexus area and nerve cell number in the myenteric plexus
not detected not increased
AChE, acetylcholinesterase.
Fig. 2. Histological findings of immunohistochemical staining using Hu C/D and CD 56. A. Ganglion cells were sparsely found in the dentate line of the anal canal (arrow head). B. Meissner plexuses were few in number and small in size in the dentate line of the anal canal (arrow head). C. The ganglion cells were still few in number in the center portion of the resected intestine (arrow head). D. Auerbach plexuses were still few in number and small in size in the center portion of the resected intestine (arrow head). E. The ganglion cells were few in number but gradually increased in the oral-side stump (arrow head). F. Auerbach plexuses were small in size but gradually increased in the oral-side stump (arrow head).
49
Journal of Pediatric Surgery Case Reports 28 (2018) 48–50
T. Furukawa et al.
extends to the total intestine [4–6,16]. Jejunostomy or ileostomy are often created as the initial operation because most patients with generalized-type IHG show a caliber change at the small intestine. However, ileostomy often causes malfunction of the fecal output and requires stoma creation with a shorter distance from the ligament of Treitz [17]. Watanabe et al. suggested that patients with IHG undergo jejunostomy at less than 50 cm from the ligament of Treitz during the neonatal period to manage IHG successfully [6]. The most common type of IHG differs between Europe and Japan. However, there have been no reports regarding such regional differences in the type of IHG. HD cases are divided into several types according to the length of the aganglionic segment. Most HD cases are short-segment aganlionosis, and extensive or total intestinal aganglionosis is rare. In contrast, the localization of IHG is extremely long in most IHG cases in Japan. Whether or not the localized type, such as colonic hypoganglionosis, and the generalized type, which requires upper jejunostomy, are the same entity is unclear at present. Further investigations are needed to elucidate these controversies regarding types of IHG. Conflict of interest The authors have no conflicts of interest to disclose. Acknowledgement The authors thank Mr. Brian Quinn for reviewing the English used in this manuscript (Japan Medical Communication, Inc.). Fig. 3. Postoperative contrast enema. No narrow segment in the residual colon.
References and an increase in the ganglion distances. However, according to a report from the fourth International Symposium on Hirschsprung disease and related neurocristopathies, held in 2004, there was broad agreement regarding the difficulty of diagnosing hypoganglionosis [7]. Some doctors do not think that hypoganglionosis really exists, so hypoganglionosis has not yet been established as an isolated entity worldwide. Histologically, in patients with hypoganglionosis, there are extremely few ganglion cells in the neonatal period, and their size is small [10]. The size of the Auerbach plexus is also small. The diameter of the nucleus of ganglion cells increases over time, but the numbers of these cells do not increase at all [10]. In immunohistochemical staining, Hu C/D is a reliable pan-neuronal marker for enteric nervous system (ENS) neurons because Hu immunoreactivity is strong in both the nuclei and cytoplasm of permanently labeled myenteric neurons [11]. Immunohistochemical staining for Hu C/D has proven useful in identifying a decrease in the number of ganglion cells in congenital isolated hypoganglionosis [12]. CD56 is particularly useful in the diagnosis of hypoganglionosis because it is a general neuronal marker staining all nerves [12,13]. In this case, Hu C/D-positive ganglion cells were sparsely found in the anal-side stump, which was located immediately proximal to the dentate line of the anal canal. There were also a few small CD56-positive Meissner plexuses in the same area. These findings are compatible with IHG. In addition, the number of ganglion cells and the size of the Auerbach plexus gradually increased as the specimens approached the oral-side stump. Although biopsies were not taken from the residual intestine, we believe that the number of ganglion cells in the residual colon is almost normal, as she achieved self-defecation after surgery with no medication. Postoperative contrast enema showed no narrow segment in the residual colon. The postoperative course of this case correlates with that of localized-type IHG. Although most cases with IHG are localized-type, such as colonic hypoganglinosis in Europe [10], the only such cases in Japan were reported by Yamataka et al. [14] and Munakawa et al. [15] as colonic hypoganglionosis in the 1990s. Since then, almost all IHG cases reported in Japan have been the generalized type, in which localization
[1] Schärli AF. Standardization of terminology of intestinal innervation disorders. Pediatr Surg Int 1995;10:440. [2] Meier-Ruge WA, Brunner LA, Engert J, Heminghaus M, Holschneider AM, Jordan P, et al. A correlative morphometric and clinical investigation of hypoganglionosis of the colon in children. Eur J Pediatr Surg 1999;9:67–74. [3] Dingemann J, Puri P. Isolated hypoganglionosis: systematic review of a rare intestinal innervation defect. Pediatr Surg Int 2010;26:1111–5. [4] Kobayashi H, Yamataka A, Lane GJ, Miyano T. Pathophysiology of hypoganglionosis. J Pediatr Gastroenterol Nutr 2002;34:231–5. [5] Kubota A, Yamauchi K, Yonekura T, Kosumi T, Oyanagi H, Mushiake S, et al. Clinicopathologic relationship of hypoganglionosis. J Pediatr Surg 2001;36:898–900. [6] Watanabe Y, Sumida W, Takasu H, Oshima K, Kanamori Y, Uchida K, et al. Early jejunostomy creation in cases of isolated hypoganglionosis: verification of our own experience based on a national survey. Surg Today 2015;45:1509–12. [7] Martucciello G, Prato AP, Puri P, Holschneider AM, Meier-Ruge WA, Jasonni V, et al. Controversies concerning diagnostic guidelines for anomalies of the enteric nervous system: a report from the fourth International Symposium on Hirschsprung's disease and related neurocristopathies. J Pediatr Surg 2005;40:1527–31. [8] Karnovsky MJ, Roots L. A "direct-colouring" thiocholine method of cholinesterase. J Histochem Cytochem 1964;12:219–21. [9] Tiffin ME, Chandler LR, Faber HK. Localized absence of the ganglion cell of myenteric plexus in congenital megacolon. Am J Dis Child 1940;59:1071–82. [10] Taguchi T, Masumoto K, Ieiri S, Nakatsuji T, Akiyoshi J. New classification of hypoganglionosis: congenital and acquired hypoganglionosis. J Pediatr Surg 2006;41:2046–51. [11] Phillips RJ, Hargrave SL, Rhodes BS, Zopf DA, Powley TL. Quantification of neurons in the myenteric plexus: an evaluation of putative pan-neuronal markers. J Neurosci Methods 2004;133:99–107. [12] Yoshimaru K, Taguchi T, Obata S, Takemoto J, Takahashi Y, Iwanaka T, et al. Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological diagnosis of congenital and acquired isolated hypoganglionosis. Virchows Arch 2017;470:679–85. [13] Nogueira A, Campos M, Soares-Oliveira M, Estevão-Costa J, Silva P, Carneiro F, et al. Histochemical and immunohistochemical study of the intrinsic innervation in colonic dysganglionosis. Pediatr Surg Int 2001;17:144–51. [14] Munakata K, Okabe I, Morita K. Hypoganglionosis. Pediatr Surg Int 1992;7:8–11. [15] Yamataka A, Fujiwara T, Nishiye H, Sunagawa M, Miyano T. Localization of intestinal pacemaker cells and synapses in the muscle layers of a patient with colonic hypoganglionosis. J Pediatr Surg 1996;31:584–7. [16] Watanabe Y, Kanamori Y, Uchida K, Taguchi T. Isolated hypoganglionosis: results of a nationwide survey in Japan. Pediatr Surg Int 2013;29:1127–30. [17] Watanabe Y, Takasu H, Sumida W. A preliminary report on the significance of excessively long segment congenital hypoganglionosis management during early infancy. J Pediatr Surg 2011;46:1572–7.
50