Hirschsprung's Disease: Clinical Guidelines

List of Abbreviations

AChE — acetylcholinesterase

HD — Hirschsprung's disease

ZAPK — sphincter apparatus of the rectum

GIT - gastrointestinal tract

ICD - International Classification of Diseases

RAIR — rectoanal inhibitory reflex

RCT — randomized clinical trial

RP — radiopharmaceutical

TSH — thyroid-stimulating hormone

Terms and Definitions

Megacolon is the dilation of the colon or the entire large intestine.

Megarectum is the dilation of the rectum.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Hirschsprung's disease (HD) is a congenital malformation of the large intestine characterized by the absence of ganglia in the submucosal and myenteric nerve plexuses of all or part of the large intestine, and sometimes the small intestine, leading to impaired innervation of the affected bowel segment, which manifests as stubborn constipation, obturation intestinal obstruction, or the picture of Hirschsprung-associated enterocolitis [1].

Synonyms: congenital colonic aganglionosis.

Dolichocolon is a developmental anomaly consisting of the elongation of the entire colon or one of its segments [31, 45, 46]. Currently, there is no universally accepted definition of dolichocolon, primarily because it remains unknown what length of the colon should be considered normal. Radiological and morphometric studies demonstrate significant variability of this parameter in normal conditions, and furthermore, their results differ substantially depending on the methodology used [31, 46, 47]. In addition, despite its presence in the International Classification of Diseases (code Q43.8, ICD-10), dolichocolon is generally not regarded as a distinct, independent nosological entity; rather, the diagnosis and management of this condition are discussed within the context of other disorders, such as constipation (code K59.0, ICD-10) and volvulus (code K56.2, ICD-10).

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The development of Hirschsprung's disease (HD) is based on various epigenetic mechanisms leading to impaired intestinal colonization by enteric stem cells derived from neural crest cells. Such defective colonization is primarily associated with impaired proliferation, survival, migration, and differentiation of enteric stem cells during the development of the enteric nervous system [2, 3, 4, 5].

The main genes controlling the aforementioned processes are: RET (receptor tyrosine kinase), GDNF (glial cell line-derived neurotrophic factor), ENDRB (endothelin receptor type B gene), and EDN3 (endothelin-3) [2, 4, 6, 7, 8].

In addition, there is a hypothesis according to which aganglionosis develops as a result of impaired differentiation of nerve cells that have already reached the intestinal wall. Various factors can affect cell maturation, such as hypoxia, exposure to chemical agents, increased radiation, and viral infection [9, 10, 57].

The accumulation of acetylcholinesterase in the mucosa, along with the absence of mediators providing an inhibitory effect in the intestinal wall, causes persistent spasm, which serves as a pathognomonic sign of HD [11, 12].

The aganglionic segment of the intestine does not participate in peristaltic activity and thus acts as a zone of functional obstruction to the passage of intestinal contents. As a result, chronic retention of fecal masses occurs in the proximal colon; over time, the latter dilates, forming megacolon, which is the main clinical sign of HD.

The cause of dolichocolon is unknown. Most authors classify dolichocolon as a developmental anomaly of the large intestine [31, 45, 46, 47], although a number of researchers allow for the possibility of an acquired nature of this condition [48, 49, 50].

1.3 Epidemiology of the Disease or Condition

According to various authors, the incidence of HD ranges from 1:30,000 to 1:5,000 total newborns [13, 14, 15].

The prevalence of colonic aganglionosis also varies among different ethnic groups. Thus, according to the California Birth Defects Monitoring Program for the period from 1983 to 1997, the frequency of HD among newborns of Asian descent was 2.8 per 10,000, among African American newborns 2.1 per 10,000, Caucasians 1.5 per 10,000, and 1 per 10,000 in Latinos [16]. In Japan, over the past 4 decades, HD has been diagnosed in approximately 1 of every 5,000 newborns [17].

There is a difference in the frequency of various forms of the disease depending on the extent of the aganglionic zone. Short-segment cases are much more common, accounting for up to 80% of the total number. The remaining 20% of observations occur in patients in whom the aganglionic segment extends proximally to the sigmoid colon [16].

In 5-8% of cases, HD is a familial disease. The risk of developing this disease in relatives is significantly higher compared to the general population [18, 41, 42].

Despite the fact that HD most often occurs as an isolated disease, the genetic role in its development is indisputable. Boys are affected 4–5 times more often than girls; however, in long-segment forms of the lesion, the sex ratio can reach 1:1–1:2. Familial cases of HD are noted in an average of 8% of patients. The risk of developing the disease in a family where the parents also have HD is 5%, in total colonic involvement up to 12%, and according to some data, when the ileum is involved, the frequency of HD development in siblings is up to 30%. Inheritance in this group is associated with a dominant gene with incomplete penetrance and has no pronounced sex predilection. Genetic studies have established at least 10 mutations in various genes in HD. The most frequent mutations are in the RET gene (7–35%), EDNRB gene (7%), and END3 gene (less than 5%). HD may also be associated with a number of chromosomal abnormalities (up to 12%), such as trisomy 21 (Down syndrome – 5–7%), congenital septal heart defects (about 4%), central hypoventilation syndrome, neurofibromatosis, multiple endocrine neoplasia type 2B, Waardenburg syndrome, Smith–Lemli–Opitz syndrome, anorectal anomalies, etc. [41].

Attempts to isolate a specific gene for Hirschsprung's disease have not been successful to date, and HD is classified among hereditary multifactorial diseases with high variability of the genetic component.

HD may occur in combination with other congenital anomalies and birth defects, such as intestinal malrotation, urogenital defects, congenital heart defects, limb malformations, cleft lip and palate, intellectual disability, hearing disorders, and other dysmorphogenetic diseases. In addition, HD can be a component of a number of genetic syndromes, such as Down syndrome, MEN type IIB, and others.

Along with genetic factors, the significance of environmental factors in the occurrence of colonic aganglionosis cannot be ignored. Like other birth defects, disorders of intestinal innervation can occur during specific periods of embryonic development. Even with a genetic predisposition, a secondary factor is required for aberrant migration of neuroblasts to the intestinal segments. Such factors may include hypoxia, exposure to chemical and radiation agents, viruses, etc. Thus, there is reason to consider Hirschsprung's disease polyetiological [41, 42].

The prevalence of dolichocolon is unknown. Due to the ambiguity of the concept itself and the lack of universally accepted diagnostic criteria, the frequency of its detection varies within very wide ranges – from 1.9% to 30% in case series descriptions [46, 52, 53].

1.4 Features of Coding the Disease or Condition

Class - Other congenital anomalies (malformations) of the digestive system (Q43) [19]:

Q43.1 - Hirschsprung's disease

Q43.8 - Other specified congenital anomalies of intestine

1.5 Classification of the disease or condition

Classification of Hirschsprung's disease [18, 20, 21, 22, 58].

Anatomical forms of the disease.

The following anatomical forms are distinguished:

• Nadanally (supranal) form - the aganglionosis zone is localized in the lower ampullary part of the rectum;

• Rectal form - underdevelopment of the intramural nervous apparatus extends to the entire rectum;

• Rectosigmoid form - aganglionosis occupies the entire rectum and part or all of the sigmoid colon;

• Subtotal form - the aganglionic segment includes the transverse colon;

• Total form — involvement of the entire large intestine, dilation of the ileum is detected. The total form of aganglionosis is always accompanied by involvement of the distal (up to 12-15 cm) or more extended section of the ileum [42].

In adult patients, according to the localization of intestinal dilation, the following are distinguished.

• Megarectum;

• Megasigmoid;

• Left-sided megacolon;

• Subtotal megacolon;

• Total megacolon;

• Megaileum.

By the degree of compensation.

• Compensated bowel condition — for many years the patient has infrequent but independent bowel movements or experiences constipation lasting from 3 to 7 days, which is easily resolved using laxatives and enemas;

• Subcompensated condition, unlike the previous one, requires intensive bowel-cleansing measures. In such cases, without the use of laxatives and enemas, independent bowel movements may be absent for over 7 days;

• Decompensated condition is characterized by the absence of the urge to defecate and independent bowel movements. In many patients, the large intestine is filled with dense intestinal contents or fecaliths. Often, even intensive measures fail to adequately evacuate the large intestine. In such cases, urgent surgical treatment is indicated.

According to the clinical course of the disease in adult patients, the following variants of the disease are distinguished:

• Typical ("pediatric") variant - severe constipation develops quite rapidly, independent bowel movements are virtually absent, and symptoms of intestinal obstruction rapidly increase;

• Prolonged variant - a slow course of the disease, when constipation can be managed for a long time using conservative measures;

• Latent variant - constipation appears for the first time after 14 years of age, and, as a rule, chronic colonic obstruction rapidly develops. The newly emerged constipation progresses, laxatives are completely ineffective, and daily enemas must be used to empty the bowel.

Classification of dolichocolon. There is no universally accepted classification of dolichocolon. Based on the predominant site of colon elongation, the following forms are distinguished:

1. Dolichosigma;

2. Left-sided dolichocolon;

3. Dolichotransversum;

4. Right-sided dolichocolon;

5. Subtotal dolichocolon;

6. Total dolichocolon [51, 59].

1.6 Clinical presentation of the disease or condition

In adult Hirschsprung's disease (HD), impaired passage through the aganglionic segment of the intestine occurs, as a result of which the proximal intestinal segments gradually dilate, forming a megacolon. The megacolon gradually progresses in the proximal direction. If left untreated, complications develop: acute intestinal obstruction, intestinal perforation, pressure ulcers of the intestinal wall caused by fecaliths, and megacolon volvulus.

Dolichocolon is usually detected during the examination of patients complaining of constipation. Accordingly, constipation, as well as associated bloating and abdominal heaviness, are most often considered as clinical manifestations of dolichocolon [31, 46, 47, 51, 52]. In addition, dolichocolon is a risk factor for intestinal volvulus, which manifests clinically as acute obturation or strangulation intestinal obstruction [31, 46, 54, 55, 56]. Sigmoid colon volvulus is the most common in clinical practice.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria for HD in adults:

• history of constipation since childhood;

• presence of a relative narrowing zone in the distal large intestine with suprastenotic dilation (megacolon) on barium enema (irrigography) images;

• absence of the rectoanal inhibitory reflex during anorectal manometry.

In doubtful cases, in the absence of a characteristic medical history, presence of an unclear radiological picture, weakened response of the internal sphincter to rectal distension, or conflicting results of these tests, a transanal Swenson rectal wall biopsy is necessary to assess the state of the intramural nerve plexus.

2.1 Complaints and Anamnesis

The main clinical symptoms in adult patients with HD include constipation and abdominal bloating, which usually begin in early childhood. However, clinical manifestations may be latent in children and develop in adulthood [64]. The main reason for seeking medical attention is constipation, which is noted by all patients. At the same time, the majority of patients experience an absence of spontaneous bowel movements. This symptom is always combined with the lack of urge to defecate. A number of patients may experience both an urge to defecate and spontaneous bowel movements, but the feeling of incomplete emptying of the large intestine persists. The presence of spontaneous bowel movements in these patients is due to the preserved propulsive capacity of the intestinal segments located proximal to the aganglionic zone [23, 24, 60].

Abdominal bloating is reported by half of the patients. This symptom occurs against the background of a prolonged absence of spontaneous bowel movements and disappears after emptying the large intestine. Abdominal pain is usually paroxysmal in nature and occurs at the peak of constipation, which is relieved by cleansing enemas [25, 26, 41, 64].

Nausea and vomiting usually appear in decompensated states, accompanied by abdominal pain and a prolonged absence of spontaneous bowel movements. A number of patients may experience weakness and malaise as a manifestation of general intoxication [27].

Adult patients practically do not develop enterocolitis, which is so characteristic of children suffering from HD [18].

2.2 Physical Examination

• All patients with suspected Hirschbrung's disease (HD) are recommended to undergo an initial appointment (examination, consultation) with a coloproctologist/surgeon, including external examination of the perianal region and assessment of the anal reflex [18, 28, 59].

GPP CLoE 5Level of Evidence/Grade of Recommendation C (level of evidence - 5).

Comment. A general physical examination must be performed in all patients with suspected HD, both to identify symptoms characteristic of HD and for differential diagnosis, assessment of somatic status, and comorbid conditions.

On physical examination, many patients show a wide subcostal angle. Against the background of bloating and enlargement of the large intestine, abdominal asymmetry and distension are noticeable, with a stretched anterior abdominal wall and visible peristalsis. At the same time, with adequately managed conservative measures, megacolon develops slowly, which helps maintain a normal abdominal shape [16, 17, 18, 41, 60, 61, 63].

In compensated states, abdominal palpation in patients with HD may be uninformative. In subcompensated and decompensated states, palpation reveals a colon distended with gas or filled with feces, most commonly the sigmoid colon. It has the shape of a balloon-like cylinder, usually located in the left half of the abdomen. If the intestine is overflowing with contents, finger impressions remain on it. In some patients, fecaliths can be palpated, which in certain observations shift within the intestinal lumen [16, 17, 18, 41, 23, 63].

Comment. Digital rectal examination of the anal canal and rectum is performed to assess the functional state of the rectal sphincter apparatus and the presence of comorbid diseases of the anal canal and rectum. In patients with a supranal form of the disease, digital examination reveals the presence of feces or coproliths in the rectal ampulla. In the case of the rectal and more extensive forms of aganglionosis, the rectal ampulla generally does not contain feces [63].

2.3 Laboratory Diagnostics

There are no specific laboratory tests for HD [18, 28, 41, 59]. Laboratory diagnostic tests should be performed in patients during the preparation and planning of surgical intervention to rule out comorbid diseases and conditions, as well as when differential diagnosis is necessary.

• In patients with megacolon and suspected secondary megacolon due to endocrinological disorders, it is recommended to test blood levels of thyroid-stimulating hormone (TSH), total calcium, and potassium to clarify the etiology of the disease [30].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

2.4 Instrumental Diagnostics

Radiological diagnostic methods make it possible to assess the functional and morphological state of the large intestine in suspected Hirschsprung's disease, which significantly affects the choice of further diagnostic and treatment tactics [18, 32, 41, 59, 61, 63]. Conversely, the detection of dolichocolon during examination does not significantly affect further management. For patients with chronic constipation in the setting of dolichocolon, the diagnostic program is formed in accordance with the guidelines for the diagnosis and treatment of chronic constipation [31, 46, 47].

• All patients with suspected HD are recommended a barium enema (irrigography) to confirm the presence of megacolon, assess its extent, and identify the radiological picture characteristic of HD [18, 31, 33, 36, 59, 61, 63].

Level of Recommendation BLevel of Evidence 3Level of Recommendation B (Level of Evidence - 3).

Comment. The main method for diagnosing megacolon is radiological - measuring the width of the intestinal lumen during its full filling, usually with a barium sulfate suspension**, under double-contrast conditions (barium enema). Normal values were obtained in two major radiomorphometric studies and proved comparable except for the width of the rectum [31, 33, 62].

Table 1. Normal lumen width of various parts of the large intestine.

The discrepancy in normal rectal diameter values between the two studies is likely explained by differences in the test methodology. Indirect confirmation of this is the fact that the upper limit of the rectal width in healthy volunteers according to defecography was 8.3 cm [34].

HD is characterized by a sharp border between the dilated colon and the relatively narrowed distal aganglionic segment of varying extent (most often the rectum, possibly involving part of the sigmoid colon) [18, 63].

In decompensated forms of the disease and markedly pronounced intestinal dilation, it can be quite difficult to determine the border of the lesion. The aganglionic segment of the intestine does not look truly "narrowed." In such cases, one should be guided by the difference in diameter between the distal and proximal parts of the intestine – if it exceeds 1.5 times, the presence of an aganglionic zone should be suspected [63].

Endoscopic diagnostic methods.

Comment. When Hirschsprung's disease is suspected, this examination is performed without special preparation. In the presence of aganglionosis, marked spasm of the distal colon wall prevents fecal masses from entering the narrowed segment, which is a pathognomonic sign of the disease. Proximal to the narrowed segment, a dilated part of the bowel containing feces is identified. In this section, smoothing and longitudinal orientation of the mucosal folds are observed, sometimes with atrophy or hyperemia [63].

Physiological diagnostic methods.

Comment. In patients with suspected Hirschsprung's disease, an important diagnostic test is anorectal manometry, specifically the assessment of the rectoanal inhibitory reflex (reflex relaxation of the internal sphincter in response to increased rectal pressure). The absence of the rectoanal inhibitory reflex is a reliable diagnostic criterion for Hirschsprung's disease with a sensitivity of 91.6% [35].

2.5 Other Procedures

Comment. Full-thickness rectal wall biopsy is of decisive importance in the diagnosis of Hirschsprung's disease. The technique was proposed by O. Swenson (1955) and consists of excising a full-thickness fragment of the rectal wall at a distance of 3 cm from the dentate line, followed by examining this area for the presence of intramural ganglia. The detection of intermuscular and submucosal nerve plexus aganglionosis is a reliable confirmation of Hirschsprung's disease. It should be borne in mind that the zone of physiological hypo- and aganglionosis can extend up to 6 cm proximal to the dentate line. To avoid false-positive results, it is recommended to perform the biopsy by excising a full-thickness 1 cm wide flap along the posterior rectal wall starting from the dentate line with a length of at least 6 cm [63].

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Radical treatment for Hirschsprung's disease in adults is currently recommended exclusively by surgical means [17, 18, 28, 41, 59, 63, 65]. Delaying surgery inevitably leads to progression of megacolon, clinical deterioration, and an increased risk of complications. Proximal spread of megacolon may necessitate more extensive bowel resection and worsen functional treatment outcomes. The development of complications may necessitate a multi-stage surgical approach [18, 41, 59, 63, 65, 66].

3.1 Surgical treatment of adult patients with Hirschsprung's disease.

The objective of treatment is to normalize the passage of intestinal contents through the colon and ensure their unobstructed evacuation via the anal canal. This goal can be achieved by excluding the aganglionic zone from intestinal transit and restoring the evacratory capacity of the proximal colon [17, 18, 41, 59, 63, 65].

Comment. This surgical intervention pursues the following objectives:

• exclusion of the aganglionic zone from intestinal transit without excessive trauma to pelvic organs;

• good functional results of surgical treatment due to preservation of the fecal continence component;

• prevention of potential injury to the internal sphincter;

• safety and asepsis in the creation of the colorectal anastomosis;

• prevention of colorectal anastomotic leakage;

• creation of conditions for optimal anastomotic function;

• reduction of postoperative complications.

The surgery is performed in two stages.

Stage one. Resection of the dilated colon and rectum with resection of the aganglionic zone and creation of a colorectal end-to-side retrorectal anastomosis with a redundancy according to Duhamel as modified by G.I. Vorobyov.

First, mobilization of the dilated colonic segments is performed with transection of the major vessels (inferior mesenteric vessels when pull-through of the left colon is performed; inferior mesenteric and middle colic vessels when pull-through of the right colon is performed). The dilated decompensated part of the colon in Hirschsprung's disease has a very characteristic appearance. The degree of dilation may vary in both size and extent, but there is always pronounced wall hypertrophy with restructuring of the outer muscular layer. This section of the bowel is usually grayish-white in color, and the outer muscular layer surrounds the intestinal wall as a dense, continuous sheath, occupying a significant part of the abdominal cavity like a coarse, semi-collapsed balloon. Haustra are absent in this section of the bowel, and blood vessels are large with multiple branches. The proximal resection margin is determined at the level where the diameter of the dilated bowel approaches normal. Next, mobilization of the aganglionic zone is performed. It is carried out as close to the bowel wall as possible to minimize trauma to the pelvic nerve plexuses. Herein, mobilization of the rectum is performed circularly up to 7-8 cm from the external anal verge, and along the posterior wall within the interfascial space down to the pelvic floor. At a height of 7-8 cm from the anal verge, the bowel is transected. The pull-through bowel is fixed to a special guide, which is passed through the retrorectal tunnel and used to bulge the posterior rectal wall immediately above the upper edge of the anal canal.

From the perineal approach, following anal divulsion, the posterior rectal wall is incised 1-2 cm above the anorectal line over the guide. 2-3 stitches are placed on the upper lip of the incision, which are subsequently used to suture the posterior rectal wall to the anterior wall of the pull-through bowel. The pull-through bowel is passed through the incision along the retrorectal tunnel using the guide. Then the guide is removed, and the redundant pull-through bowel is fixed to the perianal skin. A flatus tube is inserted into the lumen of the rectal stump.

Laparoscopic approach is feasible [44]. In such cases, a guide is not used, and the bowel pull-through is performed using forceps introduced from the perineal approach through the supra-anal incision of the posterior rectal wall.

Stage two. Transection of the redundant pull-through bowel and definitive formation of the colorectal anastomosis.

Circular transection of the redundant pull-through bowel is performed at the level of the previously placed interrupted sutures. The anastomosis is then formed by suturing the posterior rectal wall to the anterior wall of the pull-through bowel with interrupted stitches. The transection of the redundant pull-through bowel and formation of the delayed colorectal anastomosis are performed 12-15 days after the first stage [18, 24].

Comment. Indications for multi-stage surgical treatment include a weakened patient condition with severe metabolic disorders, as well as complications of Hirschsprung's disease requiring urgent intervention:

• acute intestinal obstruction;

• bowel perforation;

• colonic pressure ulcer caused by a fecalith;

• megacolon volvulus.

In such cases, the first stage involves resection of the dilated colonic segments as a Hartmann's procedure. Depending on the severity of the megacolon, resection of the sigmoid colon, resection of the left colon, or left hemicolectomy is performed. Subsequently, after stabilization of the patient's condition (usually after 6-12 months), a reconstructive pull-through of the colon is performed with the creation of a colorectal end-to-side retrorectal anastomosis according to Duhamel as modified by G.I. Vorobyov using the technique described above [18, 24].

3.2 Treatment of dolichocolon

• For patients with chronic constipation who are found to have dolichocolon during examination and have no history of intestinal volvulus, it is recommended to provide treatment in accordance with clinical guidelines for the management of constipation [31, 46, 47, 67].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

Comment. The identification of dolichocolon in patients with chronic constipation in the absence of a history of intestinal volvulus does not affect the choice of treatment tactics, is not an additional indication for surgical treatment, and, in general, is not considered a significant finding [46, 47].

• If conservative attempts to resolve dolichocolon volvulus fail, emergency surgery is recommended for all patients [54, 55, 56].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

Comment. If the bowel forming the volvulus is viable, detorsion is performed. If there are signs of impaired blood supply to the bowel, bowel wall perforation, and/or peritonitis, resection of the affected segment without primary anastomosis is performed. Subsequently, after examination and evaluation of the functional state of the remaining segments, reconstructive surgery may be performed.

3.3 Other Treatment

None.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

There are no specific rehabilitation methods for patients with Hirschsprung's disease.

If an intestinal stoma was created during surgical treatment, medical rehabilitation measures should be aimed at restoring the natural passage of intestinal contents through the gastrointestinal tract. At the same time, the nature of the surgical intervention and the extent of colon resection are determined according to the principles outlined above (see clause 3.1) [18, 59, 61, 63].

General principles of rehabilitation after surgical treatment:

1) Comprehensive assessment of the patient's baseline condition and formulation of a rehabilitation program;

2) Multidisciplinary approach to the organization of rehabilitation care. All patients who have undergone intestinal stoma formation during surgery are recommended to have a consultation and follow-up by a stoma care rehabilitation specialist.

5. Prevention and Dispensary Observation

5.1 Prevention

There are no specific preventive measures for Hirschsprung's disease. If there is a history of dolichocolon volvulus, planned surgical intervention is recommended as prevention of life-threatening complications.

5.2 Follow-up observation

• To prevent the formation of a colorectal anastomosis stricture in the early period after the Duhamel procedure, all patients are recommended to have an initial/follow-up appointment (examination, consultation) with a coloproctologist (B01.018.001 / B01.018.002) / initial/follow-up appointment (examination, consultation) with a surgeon (B01.057.001 / B01.057.002) weekly after discharge from the hospital for 1 month. Thereafter, patients are recommended to return for a follow-up examination once every 3 months for 1 year (coloproctologist appointment (examination, consultation) (B04.018.001) / surgeon appointment (examination, consultation) (B04.057.001)) [18, 39, 59, 60, 62].

GCR CGrade of recommendation C (Level of evidence - 5).

Comment: the purpose of monitoring is to assess the functional results of treatment, as well as to identify and correct late postoperative complications. One year after surgery, in addition to a clinical examination to determine the functional state of the colon and rule out megacolon recurrence, it is advisable to perform an X-ray examination of the gastrointestinal tract (barium enema or CT colography (A06.18.004.001 / A06.18.004.002 / A06.18.004.003)). In addition, if there are signs of impaired fecal continence, an anorectal manometry study can be performed.

• In the absence of late postoperative complications requiring surgical or conservative correction, adult patients are recommended to undergo a routine dispensary appointment (examination, consultation) with a coloproctologist (B04.018.001) / surgeon (B04.057.001) once a year for 3 years [18, 24, 40].

GCR CGrade of recommendation C (Level of evidence - 5).

Comment. Subsequently, patients are discharged from dispensary follow-up; consulting specialists is recommended if intestinal symptoms appear.

6. Organization of Medical Care

Planned surgical treatment should be carried out in coloproctology departments where the full range of necessary diagnostic examinations is available. Patient hospitalization can be carried out on both a planned and emergency basis. Indications for planned hospitalization include the impossibility of performing diagnostic or therapeutic procedures in an outpatient setting and the need for surgical intervention.

Emergency hospitalization can be carried out in either a coloproctology or surgery department. Indications for emergency hospitalization are complications of Hirschsprung's disease:

• acute intestinal obstruction,

• bowel perforation,

• pressure ulcer of the colon caused by a fecalith,

• megacolon volvulus.

Indications for patient discharge:

• uncomplicated course of the early postoperative period;

• controlled pain syndrome with the possibility of management using oral medications in an outpatient setting;

• the patient's ability (for patients with disabilities) to independently continue a course of conservative therapy on an outpatient basis under the supervision of a regional coloproctologist.

7. Additional Information

The prognosis for adult patients who have undergone the Duhamel operation modified by G.I. Vorobyov for Hirschsprung's disease, operated on using the methods described above, is favorable under two conditions:

• absence of late complications regarding the colorectal anastomosis;

• normal function of the anal sphincter apparatus.

Late strictures of the colorectal anastomosis can lead to the development of megacolon, therefore strict monitoring of operated patients is necessary [9, 24].

Criteria for Evaluating the Quality of Medical Care

Criteria for evaluating the quality of primary health care in adults with Hirschsprung's disease (ICD-10 codes: Q43.1, Q43.8)

Criteria for evaluating the quality of specialized medical care in adults with Hirschsprung's disease (ICD-10 codes: Q43.1, Q43.8)

References

Appendix A1. Working Group Composition

Most members of the working group are members of the Association of Coloproctologists of Russia. There is no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of the clinical guidelines:

1. Coloproctologists

2. Surgeons

3. Gastroenterologists

4. Internists

5. General practitioners (family physicians)

6. Endoscopists

7. Nursing staff

8. Medical students, residents, postgraduate students.

Table 1. Levels of Evidence (LoE) rating scale for diagnostic methods (diagnostic interventions)

Table 2. Levels of Evidence (LoE) rating scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitation interventions)

Table 3. Grades of Recommendation (GoR) rating scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Procedure for updating clinical guidelines.

The guideline revision mechanism provides for their systematic updating at least once every three years, as well as upon the emergence of new evidence-based medicine data regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

These clinical guidelines were developed taking into account the following regulatory legal documents:

1. Federal Law No. 323-FZ dated November 21, 2011 (as amended on December 28, 2024) "On the Fundamentals of Protecting Citizens' Health in the Russian Federation" (with amendments and additions, entering into force on July 1, 2025)

2. Decree of the Government of the Russian Federation No. 1968 dated November 17, 2021, "On Approval of the Rules for the Phased Transition of Medical Organizations to the Provision of Medical Care Based on Clinical Guidelines Developed and Approved in Accordance with Parts 3, 4, 6 - 9, and 11 of Article 37 of the Federal Law 'On the Fundamentals of Protecting Citizens' Health in the Russian Federation'."

3. Order of the Ministry of Health of the Russian Federation No. 206n dated April 2, 2010 (as amended on February 21, 2020) "On Approval of the Procedure for Providing Medical Care to the Population with Diseases of the Colon, Anal Canal, and Perineum in Coloproctology."

4. Order of the Ministry of Health of the Russian Federation No. 168n dated March 15, 2022, "On Approval of the Procedure for Dispensary Observation of Adults."

   5biop executive authorities for the provision of medical care in accordance with the uniform requirements of the basic compulsory health insurance program."

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Disease information. Hirschsprung's disease (congenital agangliosis) is a developmental anomaly of the colon characterized by the absence of ganglion cells in the submucous and myenteric nerve plexuses in a specific segment of the intestinal wall [18]. A ganglion is a structural form of the intrinsic nervous system of internal organs. It is a cluster of nerve cell bodies—neurons—surrounded by glial cells. Ganglions belong to the peripheral nervous system and participate in regulating the activity of internal organs. The pathogenesis of agangliosis is associated with impaired migration of neuroblasts from the vagal neural crest during embryogenesis. Since the rectum is colonized by neuroblasts last, the aganglionic zone almost always begins in the most distal part of the rectum. The earlier the migration stops, the longer the aganglionic segment [4, 5, 68].

Presumably, the aganglionic intestinal segment does not participate in peristaltic activity and thus serves as a functional obstruction to the passage of intestinal contents [16]. As a result, chronic retention of fecal matter occurs in the proximal colon, which dilates over time, forming a megacolon—the main clinical sign of Hirschsprung's disease [18, 69].

Hirschsprung's disease is a relatively rare condition, with a prevalence ranging from 1:30,000 to 1:5,000 newborns [13, 14]. Boys are affected 4–5 times more often than girls [15]. In most cases, prominent clinical manifestations such as absence of stool and severe abdominal distension appear literally from birth. Consequently, the majority of patients undergo surgical treatment in early childhood. However, in a small number of patients, symptoms may be significantly less pronounced, and only functional decompensation of the intestine or the development of complications prompts them to seek medical attention in adulthood.

The main clinical manifestations of Hirschsprung's disease are persistent constipation, typically starting in early childhood, and constant abdominal distension, independent of bowel movements. Constipation gradually progresses, and fecaliths form in the dilated sections of the large intestine, which can lead to intestinal obstruction or even bowel perforation due to stercoral ulcers, thereby necessitating emergency surgery [18].

The treatment of Hirschsprung's disease is exclusively surgical. Furthermore, the earlier the surgery is performed, the better the functional outcome. Delaying surgical intervention leads to the progression of megacolon and an increased risk of complications [24]. Surgery cannot be avoided in any case, but the proximal spread of megacolon will necessitate a more extensive bowel resection. Meanwhile, the development of complications will lead to multi-stage treatment with a much higher health risk and the likelihood of stoma formation—usually temporary, but occasionally permanent. Timely surgery allows patients to lead a full life without any restrictions. Women who have undergone the surgery have a high chance of natural conception and a full-term pregnancy.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

None.