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Megacystic, microcolon, intestinal hypoperistalsis syndrome: Possible pathogenesis
Megacystis, Microcolon, Intestinal Hypoperistalsis Syndrome: Possible Pathogenesis By Jyotsna Kirtane, Vasant Talwalker, and Darab K. Dastur Bombay, India 9 T w o cases of "'Megacystis-microcolon-intestinal hypoperistalsis s y n d r o m e " are described. These a p p e a r to be the s e v e n t h and eighth cases in published literature. C o n s i s t e n t w i t h the t w o published reports, both our patients w e r e n e w b o r n f e m a l e infants w h o m a n i f e s t e d a large bladder, associated w i t h unused colon and functional intestinal obstruction. W h i l e the earlier published reports mention a full c o m p l e m e n t of normal m a t u r e ganglion cells in all parts of the bowel, the t w o cases described here s h o w e d "'dysganglionosis'" to some e x t e n t , in the f o r m of f e w e r and shrunken neurones along w i t h o t h e r m a t u r e - l o o k i n g neurones in s o m e parts of the bowel. T h e bladder w a s available for histologic e x a m i n a t i o n only in the second case and s h o w e d a p p a r e n t l y normal innervation. Hence, it is felt t h a t the intestinal obstruction in t h e s e cases could have been due to a disturbance in bowel innervation. I N D E X W O R D S : M e g a c y s t i s microcolon intestinal hypoperistalsis syndrome; functional intestinal obstruction in n e w b o r n s .
E R D O N and his co-workers ~ reported an unusual combination of urinary and intestinal anomalies in newborn girls. These girls presented with dilated urinary tract without any obvious urinary obstruction, along with dilated upper gastrointestinal tract without any obvious obstructing lesion in its distal part. We are reporting two similar cases.
B
CASE REPORTS
Case No. 1 A 72-hour-old girl (2750 g), was admitted for distention of abdomen and failure to pass meconium. The parents were paternal first cousins. Ultrasonography examination of the mother's abdomen had shown a trilocular cyst, but it was not clear whether it was in the fetus or the mother. A caesarian section was performed as there was a possibility of this additional pathology in the mother.
From the Department of Pediatric Surgery and The Neuropathology Unit, Grant Medical College and J.J. Group of Hospitals, Bombay. Address reprint requests to Jyotsna Kirtane, MS, Grant Medical College and J.J. Group of Hospitals, Bombay 400 008, India. 9 1984 by Grune & Stratton, Inc. 002~3468/84/1902-0020501.00/0 206
The child had a massively distended abdomen. A distended bladder was palpable. There was no free fluid in the abdomen. The rectum was empty. Bile was aspirated from the stomach. A plain radiograph of the abdomen showed two gas shadows in the upper abdomen suggesting a high intestinal obstruction. The rest of the abdomen had a ground-glass appearance. An infusion pyelogram was done which showed a bilateral shell nephrogram with dilated ureters. The blood urea was 7.9 m m o l / L and serum creatinine was 137 mmol/L. Laparotomy confirmed that most of the distention of the baby's abdomen was due to the enormously dilated urinary bladder and the two kidneys. The ureters were also dilated. The stomach, duodenum and proximal 6 cm of jejunum were dilated. The rest of the bowel was foreshortened and unused. It did not show any interruption of continuity. A clinical diagnosis of aganglionosis of the entire bowel was made. Cystostomy and bilateral nephrostomy were carried out. The baby did not produce any urine in the post-operative period and died soon after the operation, probably of renal failure. At necropsy, the urethra was found to be normal. There was no obstruction at the bladder neck. The massive dilatation of the bladder and kidneys was not explained. The stomach, duodenum and proximal part of the jejunum were found to be dilated, as noted earlier at operation. The colon was also found to be unused. No obvious cause for the intestinal obstruction could be detected. Histopathologic examination was possible only on small paraffin-blocked specimens of the jejunum, ileum, transverse colon, and rectum. The myenteric plexus showed intact neurones at all the four sites, but the largest number of mature neurones was encountered in the ileum. The transverse colon and the rectum showed a number of ganglion cells, some of which appeared well formed with nucleolated nuclei (split arrow, Fig. 1) and some appeared more shrunken. The very thin distended wall of the jejunum showed more shrunken neurones (Fig. 2, arrows), and the entire myenteric plexus tissue appeared reduced in this specimen.
Case No. 2 A 4-day-old girl (2.3 kg) was admitted for failure to pass meconium and urine since birth. The child started vomiting bile within two hours of birth. X-ray showed 2 to 3 fluid levels in the upper abdomen. The rest of the abdomen was devoid of gas shadows. IVP showed a bilateral shell nephrogram, dilated ureters and a large bladder. At exploration, the proximal gastrointestinal tract including about 15 cm of jejunum, was dilated. The remaining bowel showed a gradual narrowing. Meconium was seen in the terminal ileum. There was no meconium in the colon. There were flimsy adhesions in the proximal jejunum loops, and the cecum was in the left hypochondrium. The adhesions and bands, however, were not causing a complete obstruction of the bowel. These were all released. Saline was injected in the bowel to rule out distal atresia. The bladder was deflated by introducing a catheter Journal of Pediatric Surgery, Vol. 19, No. 2 (April), 1984
MEGACYSTIS, MICROCOLON SYNDROME
207
Fig. 1. Case 1, Large mature neurons w i t h vesicular nucleolated nuclei (split arrow) and shrunken neurones in the rectum. Abundant supporting cells in the plexus. (Hematoxylin and Eosin (H and E) on paraffin section, :<800).
Fig. 3. Case 2. Photograph of autopsy specimen of case 2 showing a very large bladder. Both the kidneys show fetal Iobulations.
DISCUSSION
per urethra. In the postoperative period, the child did not pass any meconium inspite of repeated bowel washes. She became septicemic and died on the third postoperative day. At necropsy no obstruction to the urinary tract could be demonstrated. The bladder was confirmed to be enormously distended. The kidneys showed fetal lobulation (Fig. 3). The operative findings on the bowel were confirmed. The colon did not appear to be as narrow as in the first child. Histopathologic examination was carried out on different portions of the bowel, including the duodenum, jejunum, ileum, appendix, transverse colon, sigmoid colon and rectum. There was no aganglionosis of any segment examined, but a large number of mature looking ganglion cells were found only in the transverse colon and appendix, most other areas showing clumped pyknotic neurones (Fig. 4, arrows). Moreover, the rectum showed several prominent nerves in the submucosa, and only a few shrunken neurones. The bladder wall showed a number of subserosal or myenteric nerve twigs, some with a few ganglion cells and small islands of plexus tissue bearing very large neurones in the bladder neck region.
~! ~5'~
~84%
T h e r e s e e m s to be a s p e c t r u m of bowel dysf u n c t i o n in t h e n e w b o r n i n f a n t . In t h e m i l d e s t f o r m , we h a v e t h e " m e c o n i u m p l u g s y n d r o m e " w h e r e , f o l l o w i n g a r e c t a l e x a m i n a t i o n or b o w e l washes, t h e c h i l d passes a p l u g of m e c o n i u m a n d has n o r m a l b o w e l f u n c t i o n s s u b s e q u e n t l y . T h e s e cases h a v e n o r m a l g a n g l i o n cells. S i e b e r a n d G i r d a n y 2 h a v e r e p o r t e d i n f a n t s (all m a l e s ) w i t h a l m o s t t o t a l b o w e l a t o n y , h a v i n g n o r m a l distrib u t i o n of g a n g l i o n cell p o p u l a t i o n , a n d w i t h o u t any associated urological anomaly. They stressed the concept of "functional intestinal obstruction" in such cases. The most severe form of bowel dysfunction, h o w e v e r , is t h a t d e s c r i b e d by B e r d o n et al ~ in 1976, u n d e r t h e n a m e of " M e g a c y s t i s , m i c r o c o -
!ili~i; ~!~!!~i~. .~:~. . ...... ~i~!~iJ!!~!~ 84 71!!!i !i!~!~!~;:%~iiiii~ . . . . . . . . . . 84 i~i!!~ ~:: ......... iiiiiiiiiii~i~ii:i~ii~iiii~i~iiii~i~ii~ i~i!iii~ 84
~!ii~ii~!~,,~,~!~
Fig. 2. Shrunken neuronas w i t h dense pyknotic nuclei, and f e w e r supporting cells in the jeunum (H and E, x8OO).
Fig. 4. Myenteric plexus tissue in the wall of the appendix showing some larger mature neurones (long arrow) and a f e w shrunken naurones (short arrow). (H and E, x 600).
208
KIRTANE, TALWALKER, AND DASTUR
Ion, intestinal hypoperistalsis syndrome." It is seen in newborn girls presenting with complete intestinal obstruction, a large bladder and distended abdomen. There is no anatomic obstruction of the gastrointestinal tract but a foreshortened midgut which is malrotated and an unused microcolon. The intestines are said to have an abundance of mature ganglion cells in both the dilated and the nondilated parts, but they fail to function, and all patients eventually succumb. An almost identical case has been reported by A m o u r y et al 3 in 1977. W e have had the privilege of examining the sections of the bowel from their patient and noted the large number of normal neurones in A u e r b a c h ' s plexus. The two cases described by us seem to belong to "Megacystis, microcolon" syndrome, with only one significant difference. Both the children failed to show an " a b u n d a n c e of normal looking ganglion cells" in their myenteric plexuses. In the first case, only ileum had normal maturelooking ganglion cells and in the second case, only appendix and transverse colon showed normal ganglion cells. At other sites in the gastrointestinal tract most of the ganglion cells appeared abnormal, the whole cell being shrunken or with a pyknotic nucleus, and with stray normal cells. This could be considered a form of "dysganglionosis" which might have been responsible for the neurogenic dysfunction of the bowel.
T h e specimens of these two cases have been drawn from a total of about 150 biopsy, surgery or necropsy specimens of the bowel of one or another form of Hirschsprung's disease, examined by one of us (D.K.D) over the period of the last 25 years. T h e neurohistologic picture appeared to be different from that in Hirschsprung's disease in that the greater part of the narrow segment in both cases, (eg, the ileum in the first case and transverse colon in the second) showed m a t u r e neurons in the myenteric plexus. In the second child, however, the rectum showed not only few and shrunken ganglion cells but also some unusually prominent small nerves, a feature reported in Hirschsprung's disease by Garret et al. 4 N o definitive comment can be offered on the innervation of the distended bladder in the second case, but the large neurons in the small islands of plexus tissue at the base of the bladder, and the scattered ganglion cells in the subserosal nerve twigs, appear to be within normal limits, as inferred from the vesical ganglion cell distribution reported by Leibowitz and Bodian. 5 ACKNOWLEDGMENTS
Many thanks are due to the Department of Obstetrics and Gynecology, Cama and Albless Hospital, Bombay, for the ultrasonography on the first patient; and to Miss Nirmala Patkar and Mr Nanu Solanki of the Neuropathology Unit, for the histology preparation and the photomicrographs, respectively.
REFERENCES
1. Berdon WE, Baker DH, Blanc WA, et al: Megacystismicrocolon--intestinal hypoperistalsis syndrome: A new cause of intestinal obstruction in the newborn. Report of radiologic findings in five newborn girls. Am J Roentgenol Rad Ther Nucl Med 126:957-964, 1976 2. Sieber WK, Girdany BR: Functional intestinal obstruction in newborn infants with morphologically normal gastrointestinal tracts. Surgery 53:357-361, 1963 3. Amoury RA, Fellows RA, Goodwin CD, et al: Megacystis-microcolon-intestinal hypoperistalsis syndrome: A
cause of intestinal obstruction in the newborn period. J Pediatr Surg 12:1063-1065, 1977 4. Garret JR, Howard ER, Nixon HH: Autonomic nerves in rectum and colon in Hirschsprung's disease. Arch Dis Child 44:406-417, 1969 5. Leibowitz S, Bodian M: A study of vesical ganglia in children and the relationship to the megaureter megacystis syndrome and Hirschsprung's disease. J Clin Pathol 16:342350, 1963
E R D O N and his co-workers ~ reported an unusual combination of urinary and intestinal anomalies in newborn girls. These girls presented with dilated urinary tract without any obvious urinary obstruction, along with dilated upper gastrointestinal tract without any obvious obstructing lesion in its distal part. We are reporting two similar cases.
B
CASE REPORTS
Case No. 1 A 72-hour-old girl (2750 g), was admitted for distention of abdomen and failure to pass meconium. The parents were paternal first cousins. Ultrasonography examination of the mother's abdomen had shown a trilocular cyst, but it was not clear whether it was in the fetus or the mother. A caesarian section was performed as there was a possibility of this additional pathology in the mother.
From the Department of Pediatric Surgery and The Neuropathology Unit, Grant Medical College and J.J. Group of Hospitals, Bombay. Address reprint requests to Jyotsna Kirtane, MS, Grant Medical College and J.J. Group of Hospitals, Bombay 400 008, India. 9 1984 by Grune & Stratton, Inc. 002~3468/84/1902-0020501.00/0 206
The child had a massively distended abdomen. A distended bladder was palpable. There was no free fluid in the abdomen. The rectum was empty. Bile was aspirated from the stomach. A plain radiograph of the abdomen showed two gas shadows in the upper abdomen suggesting a high intestinal obstruction. The rest of the abdomen had a ground-glass appearance. An infusion pyelogram was done which showed a bilateral shell nephrogram with dilated ureters. The blood urea was 7.9 m m o l / L and serum creatinine was 137 mmol/L. Laparotomy confirmed that most of the distention of the baby's abdomen was due to the enormously dilated urinary bladder and the two kidneys. The ureters were also dilated. The stomach, duodenum and proximal 6 cm of jejunum were dilated. The rest of the bowel was foreshortened and unused. It did not show any interruption of continuity. A clinical diagnosis of aganglionosis of the entire bowel was made. Cystostomy and bilateral nephrostomy were carried out. The baby did not produce any urine in the post-operative period and died soon after the operation, probably of renal failure. At necropsy, the urethra was found to be normal. There was no obstruction at the bladder neck. The massive dilatation of the bladder and kidneys was not explained. The stomach, duodenum and proximal part of the jejunum were found to be dilated, as noted earlier at operation. The colon was also found to be unused. No obvious cause for the intestinal obstruction could be detected. Histopathologic examination was possible only on small paraffin-blocked specimens of the jejunum, ileum, transverse colon, and rectum. The myenteric plexus showed intact neurones at all the four sites, but the largest number of mature neurones was encountered in the ileum. The transverse colon and the rectum showed a number of ganglion cells, some of which appeared well formed with nucleolated nuclei (split arrow, Fig. 1) and some appeared more shrunken. The very thin distended wall of the jejunum showed more shrunken neurones (Fig. 2, arrows), and the entire myenteric plexus tissue appeared reduced in this specimen.
Case No. 2 A 4-day-old girl (2.3 kg) was admitted for failure to pass meconium and urine since birth. The child started vomiting bile within two hours of birth. X-ray showed 2 to 3 fluid levels in the upper abdomen. The rest of the abdomen was devoid of gas shadows. IVP showed a bilateral shell nephrogram, dilated ureters and a large bladder. At exploration, the proximal gastrointestinal tract including about 15 cm of jejunum, was dilated. The remaining bowel showed a gradual narrowing. Meconium was seen in the terminal ileum. There was no meconium in the colon. There were flimsy adhesions in the proximal jejunum loops, and the cecum was in the left hypochondrium. The adhesions and bands, however, were not causing a complete obstruction of the bowel. These were all released. Saline was injected in the bowel to rule out distal atresia. The bladder was deflated by introducing a catheter Journal of Pediatric Surgery, Vol. 19, No. 2 (April), 1984
MEGACYSTIS, MICROCOLON SYNDROME
207
Fig. 1. Case 1, Large mature neurons w i t h vesicular nucleolated nuclei (split arrow) and shrunken neurones in the rectum. Abundant supporting cells in the plexus. (Hematoxylin and Eosin (H and E) on paraffin section, :<800).
Fig. 3. Case 2. Photograph of autopsy specimen of case 2 showing a very large bladder. Both the kidneys show fetal Iobulations.
DISCUSSION
per urethra. In the postoperative period, the child did not pass any meconium inspite of repeated bowel washes. She became septicemic and died on the third postoperative day. At necropsy no obstruction to the urinary tract could be demonstrated. The bladder was confirmed to be enormously distended. The kidneys showed fetal lobulation (Fig. 3). The operative findings on the bowel were confirmed. The colon did not appear to be as narrow as in the first child. Histopathologic examination was carried out on different portions of the bowel, including the duodenum, jejunum, ileum, appendix, transverse colon, sigmoid colon and rectum. There was no aganglionosis of any segment examined, but a large number of mature looking ganglion cells were found only in the transverse colon and appendix, most other areas showing clumped pyknotic neurones (Fig. 4, arrows). Moreover, the rectum showed several prominent nerves in the submucosa, and only a few shrunken neurones. The bladder wall showed a number of subserosal or myenteric nerve twigs, some with a few ganglion cells and small islands of plexus tissue bearing very large neurones in the bladder neck region.
~! ~5'~
~84%
T h e r e s e e m s to be a s p e c t r u m of bowel dysf u n c t i o n in t h e n e w b o r n i n f a n t . In t h e m i l d e s t f o r m , we h a v e t h e " m e c o n i u m p l u g s y n d r o m e " w h e r e , f o l l o w i n g a r e c t a l e x a m i n a t i o n or b o w e l washes, t h e c h i l d passes a p l u g of m e c o n i u m a n d has n o r m a l b o w e l f u n c t i o n s s u b s e q u e n t l y . T h e s e cases h a v e n o r m a l g a n g l i o n cells. S i e b e r a n d G i r d a n y 2 h a v e r e p o r t e d i n f a n t s (all m a l e s ) w i t h a l m o s t t o t a l b o w e l a t o n y , h a v i n g n o r m a l distrib u t i o n of g a n g l i o n cell p o p u l a t i o n , a n d w i t h o u t any associated urological anomaly. They stressed the concept of "functional intestinal obstruction" in such cases. The most severe form of bowel dysfunction, h o w e v e r , is t h a t d e s c r i b e d by B e r d o n et al ~ in 1976, u n d e r t h e n a m e of " M e g a c y s t i s , m i c r o c o -
!ili~i; ~!~!!~i~. .~:~. . ...... ~i~!~iJ!!~!~ 84 71!!!i !i!~!~!~;:%~iiiii~ . . . . . . . . . . 84 i~i!!~ ~:: ......... iiiiiiiiiii~i~ii:i~ii~iiii~i~iiii~i~ii~ i~i!iii~ 84
~!ii~ii~!~,,~,~!~
Fig. 2. Shrunken neuronas w i t h dense pyknotic nuclei, and f e w e r supporting cells in the jeunum (H and E, x8OO).
Fig. 4. Myenteric plexus tissue in the wall of the appendix showing some larger mature neurones (long arrow) and a f e w shrunken naurones (short arrow). (H and E, x 600).
208
KIRTANE, TALWALKER, AND DASTUR
Ion, intestinal hypoperistalsis syndrome." It is seen in newborn girls presenting with complete intestinal obstruction, a large bladder and distended abdomen. There is no anatomic obstruction of the gastrointestinal tract but a foreshortened midgut which is malrotated and an unused microcolon. The intestines are said to have an abundance of mature ganglion cells in both the dilated and the nondilated parts, but they fail to function, and all patients eventually succumb. An almost identical case has been reported by A m o u r y et al 3 in 1977. W e have had the privilege of examining the sections of the bowel from their patient and noted the large number of normal neurones in A u e r b a c h ' s plexus. The two cases described by us seem to belong to "Megacystis, microcolon" syndrome, with only one significant difference. Both the children failed to show an " a b u n d a n c e of normal looking ganglion cells" in their myenteric plexuses. In the first case, only ileum had normal maturelooking ganglion cells and in the second case, only appendix and transverse colon showed normal ganglion cells. At other sites in the gastrointestinal tract most of the ganglion cells appeared abnormal, the whole cell being shrunken or with a pyknotic nucleus, and with stray normal cells. This could be considered a form of "dysganglionosis" which might have been responsible for the neurogenic dysfunction of the bowel.
T h e specimens of these two cases have been drawn from a total of about 150 biopsy, surgery or necropsy specimens of the bowel of one or another form of Hirschsprung's disease, examined by one of us (D.K.D) over the period of the last 25 years. T h e neurohistologic picture appeared to be different from that in Hirschsprung's disease in that the greater part of the narrow segment in both cases, (eg, the ileum in the first case and transverse colon in the second) showed m a t u r e neurons in the myenteric plexus. In the second child, however, the rectum showed not only few and shrunken ganglion cells but also some unusually prominent small nerves, a feature reported in Hirschsprung's disease by Garret et al. 4 N o definitive comment can be offered on the innervation of the distended bladder in the second case, but the large neurons in the small islands of plexus tissue at the base of the bladder, and the scattered ganglion cells in the subserosal nerve twigs, appear to be within normal limits, as inferred from the vesical ganglion cell distribution reported by Leibowitz and Bodian. 5 ACKNOWLEDGMENTS
Many thanks are due to the Department of Obstetrics and Gynecology, Cama and Albless Hospital, Bombay, for the ultrasonography on the first patient; and to Miss Nirmala Patkar and Mr Nanu Solanki of the Neuropathology Unit, for the histology preparation and the photomicrographs, respectively.
REFERENCES
1. Berdon WE, Baker DH, Blanc WA, et al: Megacystismicrocolon--intestinal hypoperistalsis syndrome: A new cause of intestinal obstruction in the newborn. Report of radiologic findings in five newborn girls. Am J Roentgenol Rad Ther Nucl Med 126:957-964, 1976 2. Sieber WK, Girdany BR: Functional intestinal obstruction in newborn infants with morphologically normal gastrointestinal tracts. Surgery 53:357-361, 1963 3. Amoury RA, Fellows RA, Goodwin CD, et al: Megacystis-microcolon-intestinal hypoperistalsis syndrome: A
cause of intestinal obstruction in the newborn period. J Pediatr Surg 12:1063-1065, 1977 4. Garret JR, Howard ER, Nixon HH: Autonomic nerves in rectum and colon in Hirschsprung's disease. Arch Dis Child 44:406-417, 1969 5. Leibowitz S, Bodian M: A study of vesical ganglia in children and the relationship to the megaureter megacystis syndrome and Hirschsprung's disease. J Clin Pathol 16:342350, 1963