Legal Medicine 17 (2015) 177–179
Contents lists available at ScienceDirect
Legal Medicine journal homepage: www.elsevier.com/locate/legalmed
Case Report
Pseudo-Hirschsprung’s disease with rectal hypoganglionosis: An autopsied case of circulatory failure due to severe constipation Akio Nishijima a, Seiji Shiotani b, Hideyuki Hayakawa c, Haruo Nishijima d,e,⇑ a
Department of Plastic and Reconstructive Surgery, University of Tsukuba, Tsukuba City, Ibaraki, Japan Department of Radiology, Tsukuba Medical Center, Tsukuba City, Ibaraki, Japan c Department of Forensic Medicine, Tsukuba Medical Examiner’s Office, Tsukuba City, Ibaraki, Japan d Department of Neurology, Aomori Prefectural Central Hospital, Aomori City, Aomori, Japan e Department of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan b
a r t i c l e
i n f o
Article history: Received 24 September 2014 Received in revised form 4 November 2014 Accepted 5 November 2014 Available online 28 November 2014 Keywords: Pseudo-Hirschsprung’s disease Hypoganglionosis Megacolon Postmortem computed tomography Autopsy Adult
a b s t r a c t We report a 21-year-old female patient who suddenly died of circulatory failure due to pressure from megacolon allied with pseudo-Hirschsprung’s disease. Since 3 years before her death, she had exhibited the feeling of abdominal distention, which was diagnosed as constipation. However, her constipation did not respond well to the prescribed oral administration of laxatives and enemas. She was found dead at home in the morning, lying on her back. An autopsy revealed a decreased number of ganglion cells in the rectum, suggesting hypoganglionosis. In cases of intractable chronic constipation, careful investigation of the cause of such symptoms is important. Ó 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Pseudo-Hirschsprung’s disease (PHD) is a syndrome manifested by intestinal hypoperistalsis similar to that of Hirschsprung’s disease (HD), including either an increase or decrease in the number and/or size of intramural ganglion cells [1]. Studies have reported PHD-induced death cases after chronic constipation, in which the cause of death included inflammation, necrosis, and/or perforation of the intestine [2–7]. Herein, we report an adult female patient who died due to circulatory failure because of PHD-induced megacolon, which compressed the thoracic cavity. 2. Case report A 21-year-old woman was found dead and lying on her back in the morning by her family. There were no notable abnormal findings in her birth or family history. For about 3 years before her death, she had exhibited feelings of abdominal distention, and had consulted a private clinic where she was diagnosed with constipation and had occasionally been treated with oral laxatives and ⇑ Corresponding author at: Department of Neurology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-tsukurimichi, Aomori City, Aomori 030-8553, Japan. Tel.: +81 17 726 8111; fax: +81 17 726 8325. E-mail address: [email protected] (H. Nishijima). http://dx.doi.org/10.1016/j.legalmed.2014.11.005 1344-6223/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
enemas. Severe constipation and advanced abdominal swelling were noted in a periodical health check-up, at about 4 months before her death, and she was recommended to undergo a detailed examination. However, she neglected to go to the detailed examination at the referred general hospital, and had been working until 3 days before her death. From 2 days before her death, she started to feel abdominal pain, took days off, and had rested at home. Although a criminal cause was not shown from a surface body inspection by the police, an autopsy was conducted to investigate the cause of death as it was unclear. Postmortem computed tomography (PMCT) performed 6 h after the confirmation of death showed a significantly dilated colon stuffed with feces and gas. Moreover, the diaphragm was extremely elevated, which caused compression of the chest cavity (Fig. 1). PMCT did not show a tumor, ascites, or free air. The autopsy was performed 12 h after the confirmation of death. She was 159 cm in height and 70 kg in weight. Although she was skinny in the face, chest, and limbs, her abdomen was locally torose and had a maximum abdominal circumference of 124 cm. External jugular venous distention, and marked congestion and petechiae of the bulbar and palpebral conjunctivae were observed (Fig. 2). At laparotomy, prolapse had occurred in the extremely expanded small intestine and colon, which elevated both sides of
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Fig. 3. Histological findings of the rectum. (A) Muscular layer of the most narrowed portion of the rectum of the present case. Arrows indicate Auerbach plexus (Hematoxylin and Eosin staining, 40). (B) Zoomed up image of (A). Arrows indicate ganglia. Few ganglion cells are seen in the ganglia of the Auerbach plexus (Hematoxylin and Eosin staining, 100). (C) A ganglion. An arrow indicates a ganglion near (B). Ganglion cells are seen in the ganglia of the Auerbach plexus. The cellular size was normal (Hematoxylin and Eosin staining, 100).
3. Discussion
Fig. 1. Coronal postmortem computed tomography shows that the megacolon filled with feces and gas markedly elevates the diaphragm and compresses the thorax.
Fig. 2. Autopsy photographs. (A) Left external jugular vein. Venous distention was seen. (B) Right palpebral conjunctiva. Marked congestion and petechiae were seen.
the diaphragm up to the level of the second intercostal space. Although the contents of the small intestine were soft, viscosity was increased in the colon feces towards the anus, and markedly hard feces blocked the rectum. The total weight of the small intestinal contents and feces in the colon was 23 kg. Localized stricture of the rectum was seen near the anal ring; however, there was no tumor, perforation, or necrosis in the constricted site. The other walls of the small intestine and colon were normal. Histologically, the most narrowed portion of the rectum had a decreased number of intestinal ganglion cells and thickening of the muscular layer. The cellular size was normal. No hyperplasia of nerve fibers was seen (Fig. 3). No abnormality was seen in ganglia or ganglion cells in the layers of other portions of the small intestine and colon. Therefore, the present case was diagnosed as PHD with hypoganglionosis. Test results for drugs, poison, and alcohol were negative. NTproBNP, which is an index for the circulatory condition, was high at 711 pg/mL, suggesting circulatory failure while she was still living.
Many PHD patients exhibit the feeling of abdominal distention, vomiting, delayed defecation, and severe ileus in newborns, while some PHD patients present only with persistent chronic constipation [8]. Both PHD and HD induce intestinal hypoperistalsis, though the onset age of PHD is significantly later than that of HD, and morbidity of females is higher than that of males [9]. Based on the numbers and forms of ganglion cells, PHD has been classified into the following types: hypoganglionosis, intestinal neuronal dysplasia, giant ganglia, and small ganglia [10,11]. Our PHD case may be categorized as hypoganglionosis because of the histologically-proven decreased number of ganglion cells in the constricted portion of the rectum. The autopsy showed a markedly elevated diaphragm due to a megacolon, jugular venous distention, and marked congestion and petechiae of the bulbar and palpebral conjunctivae, which suggested circulatory failure in venous return. Also, the high level of NT-proBNP indicated circulatory failure while the patient was still living. We presume that when she rolled her body over while sleeping, her chronic circulatory failure suddenly deteriorated, because she was found dead lying on her back in the morning. Therefore, it appears that our case died from circulatory failure after severe constipation due to intestinal hypoperistalsis associated with hypoganglionosis, and resulted in formation of the megacolon compressing the heart, lungs, and the inferior vena cava. Some reports on death cases associated with PHD have shown inflammation, torsion, necrosis, or perforation of the bowel [2–7]. However, to the best of our knowledge, this is the first autopsy case of PHD patient who died of circulatory failure resulting from the compression of intrathoracic organs. Our case did not visit a general hospital after being diagnosed with chronic constipation at a private clinic 3 years before her death, but had been treated with occasional oral administration of laxatives and enemas. Also, she had neglected to undergo a detailed examination 4 months before her death when her problem was pointed out during a health check-up. For a definite diagnosis of PHD, rectoanal inhibitory reflex (RAIR), barium enema, and abdominal X-ray examinations are necessary, and should be followed by biopsy of the rectal mucosa [8]. It has been reported that 100% of PHD patients are positive for RAIR [9]. The radical treatment of PHD is resection of the lesion [7,8]. However, no standardized treatment method has been established
A. Nishijima et al. / Legal Medicine 17 (2015) 177–179
because the extent of the lesion and functional condition of the bowel vary among PHD patients; conservative treatment methods are sometimes employed including the installation of enterostomy and laxatives. We believe that it would have been possible to save the life of our PHD case if adequate and timely examinations and treatments had been performed in a step-by-step manner, i.e., firstly, enterostomy treatment, and then pull-through of the colon fistula to the anus when the patient’s condition improved [7]. Chronic constipation occurs due to functional constipation in most cases [12]; however, for intractable serious constipation such as that in our case, careful causal investigation is necessary to save lives. Financial disclosures The authors have no financial support or relationships that may pose a conflict of interest. References [1] Puri P, Rolle U. Variant Hirschsprung’s disease. Semin Pediatr Surg 2004;103:293–9. [2] Ravitch MM. Pseudo-Hirschsprung’s disease. Ann Surg 1958;147:781–95.
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[3] Bentley JFR, Nixon HH, Ehrenpreis T, et al. Seminar on pseudo-Hirschsprung’s disease and related disorders. Arch Dis Child 1966;41:143–54. [4] Hayasaki T, Okada A, Saito Y, et al. Two cases of idiopathic megacolon with colonic perforation treated by emergency surgery. JAEM 2002;22:947–51 (in Japanese, Abstract in English). [5] Suzuki E, Sakibara K, Tsuji H, et al. Two cases with adult pseudoHirschsprung’s disease. Toyota Med J 2002;12:28–33 (in Japanese,Abstract in English). [6] Urushihara N, Furuta S, Fukumoto K, et al. Surgical treatment of Hirschsprung’s disease-allied disorders. Jpn J Pediatr Surg 2006;38:701–7 (in Japanese,Abstract in English). [7] Ito T, Kimura T, Yagami T, et al. Megacolon in an adult case of hypoganglionosis. Int Med 2008;47:421–5. [8] Tomita R, Kosinaga T. Allied disorders of Hirschsprung’s disease in adults. Jpn J Pediatr Surg 2006;38:778–83 (in Japanese, Abstract in English). [9] Do MY, Myung SJ, Park HJ, et al. Novel classification and pathogenetic analysis of hypoganglionosis and adult-onset Hirschsprung’s disease. Dig Dis Sci 2011;56:1818–27. [10] Kubota M. Hirschsprung’s disease and allied disorder: their pathogenesis based on electrophysiological studies. Jpn J Pediatr Surg 2006;38:666–72 (in Japanese, Abstract in English). [11] Takahashi A. Abnormal structure and distribution of cell, nerve and neurotransmitters in the intestine in cases of Hirschsprung’s disease and its allied disorders. Jpn J Pediatr Surg 2006;38:672–6 (in Japanese, Abstract in English). [12] Talley N, Weaver A. Functional constipation and outlet delay: a populationbased study. Gastroenterology 1993;105:781–90.
Contents lists available at ScienceDirect
Legal Medicine journal homepage: www.elsevier.com/locate/legalmed
Case Report
Pseudo-Hirschsprung’s disease with rectal hypoganglionosis: An autopsied case of circulatory failure due to severe constipation Akio Nishijima a, Seiji Shiotani b, Hideyuki Hayakawa c, Haruo Nishijima d,e,⇑ a
Department of Plastic and Reconstructive Surgery, University of Tsukuba, Tsukuba City, Ibaraki, Japan Department of Radiology, Tsukuba Medical Center, Tsukuba City, Ibaraki, Japan c Department of Forensic Medicine, Tsukuba Medical Examiner’s Office, Tsukuba City, Ibaraki, Japan d Department of Neurology, Aomori Prefectural Central Hospital, Aomori City, Aomori, Japan e Department of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki City, Aomori, Japan b
a r t i c l e
i n f o
Article history: Received 24 September 2014 Received in revised form 4 November 2014 Accepted 5 November 2014 Available online 28 November 2014 Keywords: Pseudo-Hirschsprung’s disease Hypoganglionosis Megacolon Postmortem computed tomography Autopsy Adult
a b s t r a c t We report a 21-year-old female patient who suddenly died of circulatory failure due to pressure from megacolon allied with pseudo-Hirschsprung’s disease. Since 3 years before her death, she had exhibited the feeling of abdominal distention, which was diagnosed as constipation. However, her constipation did not respond well to the prescribed oral administration of laxatives and enemas. She was found dead at home in the morning, lying on her back. An autopsy revealed a decreased number of ganglion cells in the rectum, suggesting hypoganglionosis. In cases of intractable chronic constipation, careful investigation of the cause of such symptoms is important. Ó 2014 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Pseudo-Hirschsprung’s disease (PHD) is a syndrome manifested by intestinal hypoperistalsis similar to that of Hirschsprung’s disease (HD), including either an increase or decrease in the number and/or size of intramural ganglion cells [1]. Studies have reported PHD-induced death cases after chronic constipation, in which the cause of death included inflammation, necrosis, and/or perforation of the intestine [2–7]. Herein, we report an adult female patient who died due to circulatory failure because of PHD-induced megacolon, which compressed the thoracic cavity. 2. Case report A 21-year-old woman was found dead and lying on her back in the morning by her family. There were no notable abnormal findings in her birth or family history. For about 3 years before her death, she had exhibited feelings of abdominal distention, and had consulted a private clinic where she was diagnosed with constipation and had occasionally been treated with oral laxatives and ⇑ Corresponding author at: Department of Neurology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-tsukurimichi, Aomori City, Aomori 030-8553, Japan. Tel.: +81 17 726 8111; fax: +81 17 726 8325. E-mail address: [email protected] (H. Nishijima). http://dx.doi.org/10.1016/j.legalmed.2014.11.005 1344-6223/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
enemas. Severe constipation and advanced abdominal swelling were noted in a periodical health check-up, at about 4 months before her death, and she was recommended to undergo a detailed examination. However, she neglected to go to the detailed examination at the referred general hospital, and had been working until 3 days before her death. From 2 days before her death, she started to feel abdominal pain, took days off, and had rested at home. Although a criminal cause was not shown from a surface body inspection by the police, an autopsy was conducted to investigate the cause of death as it was unclear. Postmortem computed tomography (PMCT) performed 6 h after the confirmation of death showed a significantly dilated colon stuffed with feces and gas. Moreover, the diaphragm was extremely elevated, which caused compression of the chest cavity (Fig. 1). PMCT did not show a tumor, ascites, or free air. The autopsy was performed 12 h after the confirmation of death. She was 159 cm in height and 70 kg in weight. Although she was skinny in the face, chest, and limbs, her abdomen was locally torose and had a maximum abdominal circumference of 124 cm. External jugular venous distention, and marked congestion and petechiae of the bulbar and palpebral conjunctivae were observed (Fig. 2). At laparotomy, prolapse had occurred in the extremely expanded small intestine and colon, which elevated both sides of
178
A. Nishijima et al. / Legal Medicine 17 (2015) 177–179
Fig. 3. Histological findings of the rectum. (A) Muscular layer of the most narrowed portion of the rectum of the present case. Arrows indicate Auerbach plexus (Hematoxylin and Eosin staining, 40). (B) Zoomed up image of (A). Arrows indicate ganglia. Few ganglion cells are seen in the ganglia of the Auerbach plexus (Hematoxylin and Eosin staining, 100). (C) A ganglion. An arrow indicates a ganglion near (B). Ganglion cells are seen in the ganglia of the Auerbach plexus. The cellular size was normal (Hematoxylin and Eosin staining, 100).
3. Discussion
Fig. 1. Coronal postmortem computed tomography shows that the megacolon filled with feces and gas markedly elevates the diaphragm and compresses the thorax.
Fig. 2. Autopsy photographs. (A) Left external jugular vein. Venous distention was seen. (B) Right palpebral conjunctiva. Marked congestion and petechiae were seen.
the diaphragm up to the level of the second intercostal space. Although the contents of the small intestine were soft, viscosity was increased in the colon feces towards the anus, and markedly hard feces blocked the rectum. The total weight of the small intestinal contents and feces in the colon was 23 kg. Localized stricture of the rectum was seen near the anal ring; however, there was no tumor, perforation, or necrosis in the constricted site. The other walls of the small intestine and colon were normal. Histologically, the most narrowed portion of the rectum had a decreased number of intestinal ganglion cells and thickening of the muscular layer. The cellular size was normal. No hyperplasia of nerve fibers was seen (Fig. 3). No abnormality was seen in ganglia or ganglion cells in the layers of other portions of the small intestine and colon. Therefore, the present case was diagnosed as PHD with hypoganglionosis. Test results for drugs, poison, and alcohol were negative. NTproBNP, which is an index for the circulatory condition, was high at 711 pg/mL, suggesting circulatory failure while she was still living.
Many PHD patients exhibit the feeling of abdominal distention, vomiting, delayed defecation, and severe ileus in newborns, while some PHD patients present only with persistent chronic constipation [8]. Both PHD and HD induce intestinal hypoperistalsis, though the onset age of PHD is significantly later than that of HD, and morbidity of females is higher than that of males [9]. Based on the numbers and forms of ganglion cells, PHD has been classified into the following types: hypoganglionosis, intestinal neuronal dysplasia, giant ganglia, and small ganglia [10,11]. Our PHD case may be categorized as hypoganglionosis because of the histologically-proven decreased number of ganglion cells in the constricted portion of the rectum. The autopsy showed a markedly elevated diaphragm due to a megacolon, jugular venous distention, and marked congestion and petechiae of the bulbar and palpebral conjunctivae, which suggested circulatory failure in venous return. Also, the high level of NT-proBNP indicated circulatory failure while the patient was still living. We presume that when she rolled her body over while sleeping, her chronic circulatory failure suddenly deteriorated, because she was found dead lying on her back in the morning. Therefore, it appears that our case died from circulatory failure after severe constipation due to intestinal hypoperistalsis associated with hypoganglionosis, and resulted in formation of the megacolon compressing the heart, lungs, and the inferior vena cava. Some reports on death cases associated with PHD have shown inflammation, torsion, necrosis, or perforation of the bowel [2–7]. However, to the best of our knowledge, this is the first autopsy case of PHD patient who died of circulatory failure resulting from the compression of intrathoracic organs. Our case did not visit a general hospital after being diagnosed with chronic constipation at a private clinic 3 years before her death, but had been treated with occasional oral administration of laxatives and enemas. Also, she had neglected to undergo a detailed examination 4 months before her death when her problem was pointed out during a health check-up. For a definite diagnosis of PHD, rectoanal inhibitory reflex (RAIR), barium enema, and abdominal X-ray examinations are necessary, and should be followed by biopsy of the rectal mucosa [8]. It has been reported that 100% of PHD patients are positive for RAIR [9]. The radical treatment of PHD is resection of the lesion [7,8]. However, no standardized treatment method has been established
A. Nishijima et al. / Legal Medicine 17 (2015) 177–179
because the extent of the lesion and functional condition of the bowel vary among PHD patients; conservative treatment methods are sometimes employed including the installation of enterostomy and laxatives. We believe that it would have been possible to save the life of our PHD case if adequate and timely examinations and treatments had been performed in a step-by-step manner, i.e., firstly, enterostomy treatment, and then pull-through of the colon fistula to the anus when the patient’s condition improved [7]. Chronic constipation occurs due to functional constipation in most cases [12]; however, for intractable serious constipation such as that in our case, careful causal investigation is necessary to save lives. Financial disclosures The authors have no financial support or relationships that may pose a conflict of interest. References [1] Puri P, Rolle U. Variant Hirschsprung’s disease. Semin Pediatr Surg 2004;103:293–9. [2] Ravitch MM. Pseudo-Hirschsprung’s disease. Ann Surg 1958;147:781–95.
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[3] Bentley JFR, Nixon HH, Ehrenpreis T, et al. Seminar on pseudo-Hirschsprung’s disease and related disorders. Arch Dis Child 1966;41:143–54. [4] Hayasaki T, Okada A, Saito Y, et al. Two cases of idiopathic megacolon with colonic perforation treated by emergency surgery. JAEM 2002;22:947–51 (in Japanese, Abstract in English). [5] Suzuki E, Sakibara K, Tsuji H, et al. Two cases with adult pseudoHirschsprung’s disease. Toyota Med J 2002;12:28–33 (in Japanese,Abstract in English). [6] Urushihara N, Furuta S, Fukumoto K, et al. Surgical treatment of Hirschsprung’s disease-allied disorders. Jpn J Pediatr Surg 2006;38:701–7 (in Japanese,Abstract in English). [7] Ito T, Kimura T, Yagami T, et al. Megacolon in an adult case of hypoganglionosis. Int Med 2008;47:421–5. [8] Tomita R, Kosinaga T. Allied disorders of Hirschsprung’s disease in adults. Jpn J Pediatr Surg 2006;38:778–83 (in Japanese, Abstract in English). [9] Do MY, Myung SJ, Park HJ, et al. Novel classification and pathogenetic analysis of hypoganglionosis and adult-onset Hirschsprung’s disease. Dig Dis Sci 2011;56:1818–27. [10] Kubota M. Hirschsprung’s disease and allied disorder: their pathogenesis based on electrophysiological studies. Jpn J Pediatr Surg 2006;38:666–72 (in Japanese, Abstract in English). [11] Takahashi A. Abnormal structure and distribution of cell, nerve and neurotransmitters in the intestine in cases of Hirschsprung’s disease and its allied disorders. Jpn J Pediatr Surg 2006;38:672–6 (in Japanese, Abstract in English). [12] Talley N, Weaver A. Functional constipation and outlet delay: a populationbased study. Gastroenterology 1993;105:781–90.
