scholarly journals Surgery, Surgical Pathology, and Postoperative Management of Patients With Hirschsprung Disease

2019 ◽  
Vol 23 (1) ◽  
pp. 23-39 ◽  
Author(s):  
Caitlin Smith ◽  
Lusine Ambartsumyan ◽  
Raj P Kapur
Keyword(s):  
Anal Canal ◽  
Transition Zone ◽  
Surgical Procedures ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Postoperative Management ◽  
Histopathological Analysis ◽  
Frozen Sections ◽  
Aganglionic Segment ◽  
Common Goals

Endorectal pullthrough surgery is integral in the treatment of patients with Hirschsprung disease. Several different surgical procedures exist, which share as common goals to excise the aganglionic segment and upstream transition zone and attach ganglionic bowel just proximal to the anal canal. The operation requires collaboration between surgeon and pathologist to localize ganglionic bowel and prevent retention of transition zone. Intraoperative frozen sections are extremely important, first to establish that ganglion cells are present and subsequently to exclude features of transition zone (partial circumferential aganglionosis, myenteric hypoganglionosis, and submucosal nerve hypertrophy) at the proximal surgical (anastomotic) margin. Postoperative histopathological analysis of resection specimens should be tailored to document distal aganglionosis, document the length of the aganglionic segment and its proximity to the anastomotic margin, and confirm that transition zone has been resected completely. Adherence to the recommendations described in this review will reduce the likelihood of transition zone pullthrough and should decrease the incidence of persistent postoperative obstructive symptoms.

Total Colonic Aganglionosis: Case Report, Practical Diagnostic Approach and Pitfalls

2010 ◽  
Vol 134 (10) ◽  
pp. 1467-1473 ◽  
Author(s):  
Raja Rabah
Keyword(s):  
Transition Zone ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Rectal Biopsy ◽  
Nerve Fibers ◽  
Submucosal Plexus ◽  
Total Colonic Aganglionosis ◽  
Biopsy Specimens ◽  
Suction Rectal Biopsy ◽  
Acetylcholinesterase Staining

Abstract Hirschsprung disease remains a challenging diagnosis for many pathologists. The disease is characterized by a lack of ganglion cells in the myenteric and submucosal plexus, associated with increased numbers of acetylcholinesterase-positive nerve fibers. Hypertrophic nerve fibers are present in most but not all patients. Total colonic aganglionosis (TCA) is an uncommon form of Hirschsprung disease with clinical, histologic, and genetic differences and is even more difficult to diagnose and manage. This case illustrates some of the difficulties frequently faced by the pathologists dealing with total colonic aganglionosis. Suction rectal biopsy specimens often lack significant nerve hypertrophy and positive acetylcholinesterase staining, which aid in the diagnosis. Pathologists have to depend mainly on the lack of ganglion cells in adequate submucosa to establish the diagnosis. Transition zone is often long in total colonic aganglionosis and interpretation of frozen sections can be difficult. The presence of several uniformly distributed clusters of mature ganglion cells and lack of nerve hypertrophy are required to avoid connections at the transition zone.

Circumferential Distribution of Ganglion Cells in the Transition Zone of Children with Hirschsprung Disease

2000 ◽  
Vol 3 (3) ◽  
pp. 216-222 ◽  
Author(s):  
Frances V. White ◽  
Jacob C. Langer
Keyword(s):  
Transition Zone ◽  
Myenteric Plexus ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Leading Edge ◽  
Marked Contrast ◽  
Surgical Specimen ◽  
Study Population ◽  
Circumferential Distribution ◽  
Pull Through

We prospectively studied the circumferential distribution of ganglion cells in the transition zone from a study population of 21 patients with Hirschsprung disease (HD) undergoing a pull-through procedure over a 26-month period. Twelve cases were satisfactory for examination, in that the transition zone was contained within a single surgical specimen and specimen distortion was minimal. Ganglion cells in the submucosa were counted in all 12 cases. In seven of the cases, the transition zone was proximal to the rectal sleeve and myenteric plexus ganglion cells were also counted. We found an uneven circumferential distribution of ganglion cells in both myenteric plexus and submucosa of the transition zone, resulting in a “leading edge” of ganglion cells extending into aganglionic distal bowel. The maximum length of this leading edge was 2.4 cm and 2.1 cm in the myenteric plexus and submucosa, respectively. Ganglion cells at the tip of the leading edge were present in clusters of up to six ganglion cells, in marked contrast to an absence of ganglion cells for most of the remainder of the circumference. Closely spaced myenteric plexus ganglia were seen at the tip of the leading edge in some cases. The leading edge was more frequently observed along the antimesenteric side, but this was not statistically significant. Our findings have relevance in the interpretation of intraoperative biopsies at the time of pull-through surgery and subsequent biopsies of neorectum in patients with surgically corrected HD.

Reoperation for Hirschsprung Disease: Pathology of the Resected Problematic Distal Pull-Through

2012 ◽  
Vol 15 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Alexander Coe ◽  
Margaret H. Collins ◽  
Taiwo Lawal ◽  
Emily Louden ◽  
Marc A. Levitt ◽  
...  
Keyword(s):  
Transition Zone ◽  
High Power ◽  
Ganglion Cells ◽  
Frozen Section ◽  
Hirschsprung Disease ◽  
Postoperative Outcome ◽  
Surgical Removal ◽  
High Power Field ◽  
Pull Through ◽  
Poor Outcomes

Hirschsprung disease, which consists of aganglionosis of the rectum and sometimes more proximal bowel, requires surgical removal of the aganglionic bowel and creation of ganglionated neorectum using proximal normally innervated bowel. The border between aganglionic and ganglionic bowel is irregular; the transition zone features variable quantities of ganglion cells and numerous large nerves. We report the histopathology of pull-through bowel segments resected because of poor postoperative outcome from 30 patients (22 boys, 8 girls). The most common indication for reoperation was severe constipation/obstruction. Transition zone (bowel with at least two nerves ≥40 μm diameter per 400× high-power field, and ganglion cells) or aganglionic bowel (bowel with at least two nerves ≥40 μm per high-power field diameter, but without ganglion cells) was found in 19/30 (63%) resections. In colons resected because of familial adenomatous polyposis, rare high-power fields showed two enlarged nerves; the mean age of those patients (135 ± 49.4 months) was significantly higher than that of the patients undergoing redo pull-through surgery (67.9 ± 42.8 months). Additional pathology included stricture and enterocolitis. Although there are multiple causes for poor outcomes following surgical therapy for Hirschsprung disease, abnormal innervation of the bowel used for pull-through is common. We recommend that intraoperative consultation at primary pull-through procedure include frozen section evaluation of the circumference of the bowel to be used for pull-through to confirm histologically the presence of both ganglion cells and normal-caliber nerves. The criteria used in this study are most suitable for infants and young children.

NOX5 is Expressed Aberrantly but Not a Critical Pathogenetic Gene in Hirschsprung Disease

2020 ◽  
Author(s):  
Jing Wang ◽  
Jun Xiao ◽  
Xinyao Meng ◽  
Xufeng Chu ◽  
DiDi Zhuansun ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Zebrafish Embryo ◽  
Ganglion Cells ◽  
Mrna Level ◽  
Hirschsprung Disease ◽  
Cell Stage ◽  
Aganglionic Segment ◽  
And Control ◽  
Gi Motility

Abstract Background:Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of intramural ganglion cells in the distal gastrointestinal tract (GI), which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. Recent studies have suggested NADPH oxidase 5 (NOX5) as a candidate risk gene for HSCR. In this study, we examined the function of NOX5 to verify its role in the development of enteric nervous system (ENS).Methods: HSCR tissue specimens (n = 10) were collected at the time of pull-through surgery and control specimens (n = 10) were obtained at the time of colostomy closure in patients. The NOX5 expression in aganglionic and ganglionic segments of HSCR colon and normal colon were analyzed by immunohistochemistry (IHC), western blot and RT-qPCR. The gene expression levels and spatiotemporal expression spectrum of NOX5 in different development stages of zebrafish embryo were investigated using real-time quantitative PCR (RT-qPCR) and in-situ hybridization (ISH). The enteric nervous system in NOX5 Morpholino (MO) knockdown and wild type (WT) zebrafish embryo was analyzed by whole-mount immunofluorescence (IF). Intestinal transit assay was performed to analyze the gastrointestinal motility in NOX5 knockdown and control larvae.ResultsNOX5 is strongly expressed in the ganglion cells in the proximal segment of HSCR colons and all segments of normal colons. Moreover, the expression of NOX5 is markedly decreased in the aganglionic segment of HSCR colon compared to the ganglionic segment. In zebrafish, NOX5 mRNA level is the highest in one cell stage embryos and it is decreased by the development of the embryos. Interestingly, the expression of NOX5 appears to be enriched in the nervous system. However, the number of neurons in the GI tract and the GI motility were not affected upon NOX5 knockdown.ConclusionsNOX5 may play a role in the early development of zebrafish embryo, but not required for the ENS development and loss of NOX5 didn’t affect the GI motility in zebrafish. Nevertheless, we demonstrated that NOX5 specifically expressed in the ganglionic cell in colon tissue and markedly decreased in the aganglionic segment.

scholarly journals Are We Underdiagnosing Hirschsprung Disease?

2019 ◽  
Vol 23 (1) ◽  
pp. 60-71
Author(s):  
Raj P Kapur ◽  
Lusine Ambartsumyan ◽  
Caitlin Smith
Keyword(s):  
Transition Zone ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Rectal Biopsy ◽  
Cholinergic Innervation ◽  
Short Segment ◽  
Recent Improvement ◽  
Recent Trends ◽  
Mucosal Innervation ◽  
Rectal Biopsies

Hirschsprung disease (HSCR) is conventionally defined as aganglionosis of the distal rectum and a variable length of proximal contiguous bowel with a transition zone of ganglionic, but neuroanatomically abnormal, bowel located immediately upstream. Recent improvement in our understanding of the pathology and genetics of HSCR and relevant animal models indicates highly variable expressivity. The spectrum of intestinal neuropathology includes patients with very short-segment aganglionosis, limited to the distal 1 to 2 cm of the rectum, and possibly patients with no true aganglionic segment, but nonphysiological transition zone pathology in their distal rectums. The presence or absence of submucosal ganglion cells in a rectal biopsy is not sufficient to exclude these patients, in whom submucosal nerve hypertrophy and/or abnormal cholinergic mucosal innervation may be the only diagnostic clues. In addition, diagnosis or exclusion of HSCR by rectal biopsy now relies in part on mucosal patterns of calretinin immunohistochemistry, with less emphasis on submucosal tissue adequacy and assessment of cholinergic innervation. These recent trends in the surgical pathology approach to rectal biopsies may miss patients at the phenotypically milder end of the malformation spectrum, with profound implications for subsequent management, prognosis, and genetic counseling.

scholarly journals NOX5 is expressed aberrantly but not a critical pathogenetic gene in Hirschsprung disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Wang ◽  
Jun Xiao ◽  
Xinyao Meng ◽  
Xufeng Chu ◽  
Di Di Zhuansun ◽  
...  
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Zebrafish Embryo ◽  
Ganglion Cells ◽  
Mrna Level ◽  
Hirschsprung Disease ◽  
Cell Stage ◽  
Real Time Quantitative Pcr ◽  
Aganglionic Segment ◽  
And Control

Abstract Background Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of intramural ganglion cells in the distal gastrointestinal tract (GI), which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. Recent studies have suggested NADPH oxidase 5 (NOX5) as a candidate risk gene for HSCR. In this study, we examined the function of NOX5 to verify its role in the development of the enteric nervous system (ENS). Methods HSCR tissue specimens (n = 10) were collected at the time of pull-through surgery and control specimens (n = 10) were obtained at the time of colostomy closure in patients. The NOX5 expression in aganglionic and ganglionic segments of HSCR colon and normal colon were analyzed by immunohistochemistry (IHC), western blot and real-time quantitative PCR (qPCR). The gene expression levels and spatiotemporal expression spectrum of NOX5 in different development stages of zebrafish embryo were determined using qPCR and in-situ hybridization (ISH). The enteric nervous system in NOX5 Morpholino (MO) knockdown and wild type (WT) zebrafish embryo was analyzed by whole-mount immunofluorescence (IF). Intestinal transit assay was performed to analyze the gastrointestinal motility in NOX5 knockdown and control larvae. Results NOX5 is strongly expressed in the ganglion cells in the proximal segment of HSCR colons and all segments of normal colons. Moreover, the expression of NOX5 is markedly decreased in the aganglionic segment of HSCR colon compared to the ganglionic segment. In zebrafish, NOX5 mRNA level is the highest in the one cell stage embryos and it is decreased overtime with the development of the embryos. Interestingly, the expression of NOX5 appears to be enriched in the nervous system. However, the number of neurons in the GI tract and the GI motility were not affected upon NOX5 knockdown. Conclusions Our study shows that NOX5 markedly decreased in the aganglionic segment of HSCR but didn’t involve in the ENS development of zebrafish. It implies that absence of intestinal ganglion cells may lead to down-regulation of NOX5.

Characterization of the Transition Zone in Short Segment Hirschsprung Disease Using Calretinin Immunostaining

2021 ◽  
pp. 109352662110539
Author(s):  
Franziska Righini-Grunder ◽  
Dorothée Bouron-Dal Soglio ◽  
Lara Hart ◽  
Ann Aspirot ◽  
Christophe Faure ◽  
...  
Keyword(s):  
Transition Zone ◽  
Ganglion Cells ◽  
Short Form ◽  
Hirschsprung Disease ◽  
Nerve Fibers ◽  
Normal Density ◽  
Short Segment ◽  
Pull Through ◽  
Distal Border ◽  
Proximal Border

Introduction: The detailed expression pattern of calretinin immunohistochemistry in the transition zone (TZ) of Hirschsprung disease (HSCR) has not yet been reported. This study aims to examine the value of calretinin immunohistochemistry for more accurately determining the distal and proximal border of the TZ in short segment HSCR. Methods: Specimens of pull-through surgery from 51 patients with short form of HSCR were analyzed on two longitudinal strips using hematoxylin and eosin (H&E) staining and calretinin immunohistochemistry. Results: In all but two patients, the first appearance of calretinin expression was seen on mucosal nerve fibers before the appearance of any ganglion cells, indicating the distal border of the TZ. The maximum distance between the distal border of the TZ and the proximal border of the TZ, defined by ganglion cells in a normal density on H&E stained sections, a strong calretinin expression on mucosal nerve fibers and in >80% of submucosal and myenteric ganglion cells, with no nerve hypertrophy and absence of ganglionitis was 60 mm. Conclusion: The distal border of the TZ is characterized by calretinin positive intramucosal neurites in nearly all of short form of HSCR and not by calretinin expression on ganglion cells.

scholarly journals Ultrashort-segment Hirschsprung disease in a 4-year-old female

2020 ◽  
Vol 2020 (9) ◽  
Author(s):  
Alejandra Rodas ◽  
Sabrina Barillas ◽  
Javier Ardebol
Keyword(s):  
Congenital Anomalies ◽  
Pediatric Surgery ◽  
Intestinal Tract ◽  
Neonatal Period ◽  
Clinical Symptoms ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Distal Portion ◽  
Congenital Megacolon ◽  
Aganglionic Segment

Abstract Hirschsprung disease (HSCR) is characterized by the absence of neuronal ganglion cells in a distal portion of the intestinal tract [1]. In 1691, Frederick Ruysch described the disease as congenital megacolon. HSCR-associated congenital anomalies have been reported in 5–32% of affected patients [2]. The clinical symptoms of HSCR are usually evident in the neonatal period. However, in some cases where the extent of the aganglionic segment is short, symptoms may become clinically relevant later in childhood [3]. HSCR is one of the most difficult diseases to identify in pediatric surgery due to its multiple clinical, histological and radiological variations [2, 3]. The goal of surgical management is to remove the aganglionic segment and reconstruct the intestinal tract through techniques such as Swenson, Duhamel and Soave [4]. The following case consists of a 4-year-old patient with a chronic presentation of constipation secondary to ultrashort-segment Hirschsprung disease.

Autopsy Study of Calretinin Immunohistochemistry in the Anorectal Canal in Young Infants and Potential Implications for Rectal Biopsy Approach in the Neonatal Period

2021 ◽  
pp. 109352662110301
Author(s):  
Heather Rytting ◽  
Zachary J Dureau ◽  
Jose Velazquez Vega ◽  
Beverly B Rogers ◽  
Hong Yin
Keyword(s):  
Neonatal Period ◽  
Ganglion Cells ◽  
Hirschsprung Disease ◽  
Rectal Biopsy ◽  
Autopsy Study ◽  
Pathologic Diagnosis ◽  
Young Infants ◽  
Autopsy Specimens ◽  
Pectinate Line ◽  
Age Range

Background Absent submucosal ganglion cells in biopsies 1-3 cm above the pectinate line establishes the pathologic diagnosis of Hirschsprung Disease (HD). Calretinin stains both ganglion cells and their mucosal neurites and has gained importance in HD diagnosis. Absent calretinin positive mucosal neurites in biopsies at the appropriate level above the pectinate line is highly specific for HD. Whether this applies to lower biopsies is uncertain. To address this, we studied anorectal canal autopsy specimens from infants. Methods We performed an autopsy study of infant anorectal canal specimens to describe calretinin staining in this region. Calretinin staining was correlated with histologic and gross landmarks. Results In all 15 non-HD specimens, calretinin positive mucosal neurites were present in glandular mucosa up to the anorectal line where neurites rapidly diminished. Age range was preterm 26 weeks to 3 months. Conclusions Calretinin positive mucosal neurites are present in glandular mucosa up to the anorectal line in young infants. This is potentially important regarding neonatal HD biopsy level and diagnosis. Positive calretinin staining at the anorectal line favors normal innervation making HD unlikely. Absent calretinin positive neurites in glandular mucosa is worrisome for HD in young infants, regardless of location.

scholarly journals Pullthrough Operation for Hirschsprung's Disease: Importance of a Circumferential (Donut) Biopsy at the Level of the Anastomosis

2019 ◽  
Vol 07 (01) ◽  
pp. e55-e57
Author(s):  
Susan Jehangir ◽  
Soundappan Venkatraman Sannappa Soundappan ◽  
Micheal Krivanek ◽  
Susan Arbuckle ◽  
Nicole Graf
Keyword(s):  
Transition Zone ◽  
Transverse Colon ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Ganglion Cells ◽  
Distal Colon ◽  
Dentate Line ◽  
Full Thickness ◽  
Mesenteric Border ◽  
Antimesenteric Border

AbstractHirschsprung's disease is characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction. It is managed by excision of the aganglionic segment and anastomosis of the ganglionated bowel just above the dentate line. The level of aganglionosis is determined by performing multiple seromuscular biopsies and/or full thickness biopsy on the antimesenteric border of the bowel to determine the level of pullthrough. The transition zone is described as being irregular, and hence a doughnut biopsy is recommended so that the complete circumference can be assessed. Herein, we described a child in whom there was a selective absence of ganglion cells in 30% of the circumference of the bowel along the mesenteric border for most of the transverse colon. This case defies the known concept of neural migration in an intramural and transmesenteric fashion and emphasizes the importance of a doughnut biopsy of the pulled-down segment.

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