Ludzkie koronawirusy - autor: Krzysztof Pyrć z Zakładu Mikrobiologii, Wydział Biochemii, Biofizyki i Biotechnologii, Uniwersytet Jagielloński, Kraków

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© Borgis - Nowa Medycyna 2/2017, s. 59-72
*Marta Zelga1, Piotr Zelga2, Adam Dziki2, Anna Piaseczna-Piotrowska1
Hirschsprung disease in children and adults – updates on clinical knowledge for general surgeons
Choroba Hirschsprunga u dzieci i dorosłych – kompendium wiedzy dla chirurga ogólnego
1Department of Pediatric Surgery, Urology and Transplantology, Polish Mother’s Memorial Hospital Research Institute in Łódź
Head of Department: Professor Anna Piaseczna-Piotrowska, MD, PhD
2Department of General and Colorectal Surgery, Medical University of Łódź
Head of Department: Professor Adam Dziki, MD, PhD, FACS, FACRS
Streszczenie
Choroba Hirschsprunga (HD) jest wrodzoną wadą przewodu pokarmowego, rzutującą na dalsze życie chorego. Od czasu pierwszych doniesień w XIX wieku, odnotowano znaczny postęp w zrozumieniu neuropatologii tej choroby i skutecznym leczeniu w okresie wieku dziecięcego i u dorosłych. Wprowadzono techniki małoinwazyjne, zredukowano liczbę operacji do jednego etapu z dostępu kroczowego oraz skutecznie leczy się powikłania, z których najbardziej poważnym pozostaje pooperacyjne zapalenie jelita cienkiego i okrężnicy związane z chorobą Hirschsprunga (HAEC). Przezodbytnicza resekcja odcinka bezzwojowego (TEPT) stała się dominującą metodą leczenia z uwagi na: techniczną łatwość zabiegu, dostęp kroczowy i uzyskiwane dobre wyniki czynnościowe. Stosowanie tej metody wiąże się jednak z większym ryzykiem występowania HAEC. HD może również występować u dorosłych, sprawiając istotne trudności diagnostyczne. Pacjenci skarżą się na przewlekłe zaparcia oraz bóle brzucha. W przypadku stwierdzonej HD u dorosłych operacja sposobem Duhamela jest leczeniem z wyboru, a w niektórych przypadkach można stosować miotomię przezodbytniczą. W celu zmniejszenia chorobowości i śmiertelności po zabiegach stosowanych w leczeniu HD zarówno u dzieci, jak i u dorosłych zaleca się centralizację leczenia w dużych ośrodkach z powodu trudnego procesu diagnostycznego i zaawansowanych technik operacyjnych.
Summary
Hirschsprung’s disease is a congenital disorder of the gastrointestinal duct with lifelong consequences. Since the first reports on the disease in the XIX century, significant progress has been noted in the understanding of the neuropathology of this disease, as well as in the effective treatment in new-borns, children and in adults. Minimally invasive techniques have been introduced, the number of surgical operations has been reduced to one stage with perineal access and there is effective treatment of complications, of which post-operative inflammation of the small intestine and of the colon associated to Hirschsprung’s disease remains the most serious one. Transanal resection of the aganglionic section (TEPT) has become the dominant method of treatment due to the technical easiness of the procedure, perineal access and the obtained good functional results. However, the application of this technique is associated with a higher risk of the occurrence of HAEC. HD may also occur in adults causing significant diagnostic difficulties. The patients complain of chronic constipations and abdominal pain. In case of diagnosing HD in adults an operation performed using the Duhamel technique is the treatment of choice and in selected cases transanal myotomy may be applied. In order to reduce the morbidity and mortality after the procedures applied in the treatment of HD both in children and in adults it is recommended to centralize treatment in big centres due to the difficult diagnostic process and advanced surgical techniques.
Słowa kluczowe: zaparcia,
Introduction
Hirschsprung’s disease is a congenital functional disorder of gastrointestinal motility resulting from the absence of ganglions in the enteric nerve plexus starting from the internal anal sphincter and extending proximally to a various length of the intestine. The aganglionic section is contracted and it constitutes a mechanical barrier for the propulsion of intestinal contents. This disorder is the result of the stopping of the migration of primary nerve cells coming from the neural crest in early fetal life, which may be caused by genetic factors (RET, GDNF genes etc.), the incorrect structure of the extracellular matrix proteins (fibronectin, laminin etc.), a deficiency of neurotrophic factors (NGF, NT-3 etc.) and of cell adhesion molecules (NCAM, LiCAM). Most frequently the changes are limited to the rectum and the sigmoid colon (75% of cases). Less frequently aganglionosis reaches the splenic flexure (15%). In 6% of cases there is a lack of autonomic innervation in the whole large intestine (TCA – total colonic aganglionosis). The disease may also sporadically affect the whole small intestine and even the duodenum. There are also reports of the ultra-short form of the disease affecting only a 2-3 cm section of the rectum above the pectinate line. In 70% of cases the disease occurs as an isolated anomaly, in the remaining cases it frequently constitutes a component of syndromes, e.g. the Down syndrome, the Wardenburg syndrome. According to the data of the European Surveillance of Congenital Anomalies (EUROCAT) gathering registers of congenital anomalies from 31 European countries, the prevalence of the disease is estimated to be 1.09 in 10 000 childbirths with the observed trend towards higher prevalence during the last 20 years (1). On the basis of the statistical data of the Polish Registry of Congenital Malformations covering the years 2005-2006 in Poland 25 cases of the disease were reported (0.4/10 000 childbirths) including 1 in the Łódź Voivodship (0.2/10 000 childbirths) (2). However it is believed that the scale of prevalence of this disease is much higher. In 80% of cases this disease is diagnosed during the first year of life. In the period of puberty and adulthood it is rare (most frequently it is the ultrashort form of the disease). Children with a suspicion of HD are most frequently referred to multi-specialty paediatric centres offering the possibility of appropriate diagnostics and surgical treatment. Depending on the clinical condition, the possibility of the occurrence of complications resulting both from the nature of this anomaly and from the applied treatment, postsurgical supervision usually lasts for 3 years or more and regular follow-up appointments should be held until reaching adulthood. In adulthood patients are usually referred to a Gastroenterological or Surgical Clinic due to ailments such as faecal incontinence or constipations. These Clinics are also places where patients with undiagnosed congenital aganglionosis are referred to – these are often patients who for years were treated for chronic constipations, recurrent abdominal pain or the symptoms of the irritable bowel. Patients with acquired aganglionosis (Chagas’ disease) are very rare.
Clinical symptoms of HD
Ca. 80-90% of children with HD show symptoms already in the neonatal period. These are: delayed expulsion of meconium occurring later than in the 24th hour of life, constipations, abdominal distension, periodically recurrent diarrhoea (enterocolitis). These symptoms may be the cause of septicaemia and may directly threaten the life of the new-born child. The main symptoms are chronic constipations resistant to conservative treatment, abdominal distensions, gradual delay in the physical development of the child. An element which draws attention in the per rectum examination is the empty contracted rectal ampulla. Unexplained perforations of the intestine in the absence of inflammatory changes of the intestinal wall, especially the cecum, may cause the suspicion of HD.
Adult patients complain mainly of constipations which – to a varying extent – persist since childhood and do not regress after the applied conservative treatment. This is accompanied by abdominal distension (83-86%) and periodical abdominal pain (40-80%), especially in case of long periods between defecations. Patients take laxatives chronically or do enemas on themselves (3). In contrary to the case of children, faecal incontinence in adults is a rare symptom of HD. The disease may also be manifested through the occurrence of “acute” surgical diseases such as the obstruction of the gastrointestinal tract, toxic megacolon or the intussusception of the sigmoid colon (4, 5).
Disease diagnostics
In paediatric surgery suction biopsy of the rectum currently constitutes the basic method of taking biopsy specimens from the rectal mucosa or submucosa aimed at confirming or excluding the occurrence of Hirschsprung’s disease. It is also the basis for the qualification for surgical treatment applying the TEPT method. The condition for reliable assessment is taking a bioptate of appropriate size (material sufficient for performing ca. 100 cross-sections), appropriate thickness (containing the submucosa) and appropriate location (0.5-1.5 cm over the pectinate line depending on the child’s age). Currently, due to the risk of complications and the necessity to apply anesthesia to the child, surgical biopsy is performed rarely (6). During laparoscopy/laparotomy in turn bioptates are taken in order to determine the extent of aganglionosis. The presence of ganglion cells and the occurrence of hypertrophy of nerve fibers are determined in the taken bioptate. Various types of histochemical and immunohistochemical examinations of the histological specimens of the taken bioptates are performed applying reagents (such as eosin and haematoxylin, acetylcholinesterase, lactate dehydrogenase and succinate dehydrogenase, NADPH-D) or antibodies (calretinin, PGP9.5, peripherin, Substance P, NO-synthase etc.). A characteristic feature of the HD image is the absence of nerve cells and nervous ganglions in the enteric nervous plexus and the hypertrophy of nerve fibers in the intestinal wall. The sensitivity and specificity of the suction biopsy in the diagnostics of Hirschsprung’s disease is determined respectively at: 97-100% and 99-100% and the risk of complications is lower than 1% (7-10).
Anorectal manometry and radiological examinations play a supplementary role in making the diagnosis but their sensitivity and specificity is significantly lower than in the case of biopsy. The manometric examination is performed mainly in order to determine the presence of the relaxation reflex of the internal anal sphincter which develops in the first month of life. The lack of relaxation of the sphincter in response to the pressure increase in the rectal ampulla is characteristic for Hirschsprung’s disease. The sensitivity and specificity of this method are assessed to be 75-100% and 85-97% (11, 12).
Radiologic studies are often performed first due to their low invasiveness and availability. A plain X-ray of the abdominal cavity in a hanging position allows for demonstrating distended loops of the large intestine, the presence of air-fluid levels. Lower gastrointestinal series displays the funnel-shaped area of the transition zone – the “cone-shape syndrome” at the border between the ganglionic intestine and the contracted aganglionic intestine. A late X-ray image after 24 hours displays the retention of the contract medium in the distal section of the intestine. The contrast examination is performed without the prior preparation of the intestines and its sensitivity and specificity differ depending on the length of the aganglionic fragment of the intestine and the age of the patient (70 and 83%) (13). Lower sensitivity and specificity of the examination is observed in case of short aganglionic sections and in neonatal age in which the transition zone is less developed (14).
Operational treatment in children
Operational treatment is the only method which gives a chance for curing the patient (15). The idea of the operational treatment of Hirschsprung’s disease is based on cutting out the aganglionic section of the intestine, bringing the nerved intestine closer to the distal part of the rectum (pull-through) and joining them together as close as possible to the anus (anastomosis).
The first successful operation based on the removing of the aganglionic part of the intestine and pulling the healthy fragment through the everted rectum was performed by Swenson and Bill in 1948. From that time new techniques were developed; they differed from the first operation which was also further modified. The surgical treatment of HD was primarily composed of three stages of the operation, i.e. forming a stoma above the transition zone, performing the repair surgical procedure and next closing the colostomy. Currently there is a strive to reduce the number of planned interventions aiming at performing one-stage interventions. Such procedure is becoming more and more common and the results are comparable or better than in case of multi-stage operations (16-18). However performing a diverting colostomy is still recommended in children with acute inflammation of the intestines related to Hirschsprung’s disease (HAEC), malnutrition or a high risk of perforation e.g. as a result of intestine distension (5). The most frequently applied surgical techniques have been presented in table 1.
Tab. 1. The operational techniques most frequently applied in children with Hirschsprung’s disease
Type of operationSwensonDuhamelSoaveRehbeinTEPT
Procedure description– intra-abdominal resection of the aganglionic intestine
– preparating and mobilisation of the rectum
– eversion of the rectum outside through the anus
– pull-through of the ganglionic intestine through an incised rectal wall
– anastomasis of the pulled-through intestine with the rectal wall
– the resection of the closer part of the aganglionic intestine
– transanal anastomasis of the nerved intestine with the back wall of the rectal stump using a stapler
– mucosectomy of the aganglionic section of the intestine
– pull-through of the healthy intestine through the cuff
– anastomasis with the anus ca. 1 cm above the pectinate line
– resection of the aganglionic section of the intestine with leaving a ca. 4 cm aganglionic fragment in the retroperitoneal area
– colorectal anastomasis performed using a stapler
– transanal removal of the aganglionic section
– pull-through of the nerved intestine from the abdominal cavity through the left muscular cuff of the distal part of the rectum
– anastomatis of the pulled-through intestine with the mucosa of the anal canal just above the pectinate line
Number of stages of the procedure1-31-31-31-31-3
Operational accessabdomino-perinealabdomino-perineal or pull-throughperineo-abdominal or pull-throughabdominalperineal
Laparoscopic surgeryyesyesnoyesyes
Frequency of feacal incontinence3.2-19.5%0-27%2.1%8.9%0-21%
The results of surgical treatment depend on many factors including the experience of the operator, the type of the anomaly – especially the length of the aganglionic section, postoperative complications and the commitment of the patient’s carers or the patient him- or herself to the solicitude of regular defecation. Also other factors affecting the treatment results have been identified. These are: male sex, accompanying congenital defects of the central nervous system, meconium ileus and the occurrence of intestine inflammation before applying operative treatment (19).

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otrzymano: 2017-04-05
zaakceptowano do druku: 2017-04-27

Adres do korespondencji:
*Marta Zelga
Klinika Chirurgii, Urologii Dziecięcej i Transplantologii Instytut Centrum Zdrowia Matki Polki w Łodzi
ul. Rzgowska 281/289, 93-338 Łódź
tel. +48 669-639-894
martaswitkowska@gmail.com

Nowa Medycyna 2/2017
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