Intestinal Angiodysplasia: Clinical Guidelines

List of Abbreviations

GIT – gastrointestinal tract

MRI – magnetic resonance imaging

CT – computed tomography

Terms and Definitions

Angiodysplasia — a pathological condition characterized by defective (pathological) development and structure of the blood vessels of the intestinal wall.

Congenital angiodysplasia — a disease in which pathological development of the intestinal wall vessels forms during the intrauterine period.

Acquired angiodysplasia is a condition caused by the acquired pathological (abnormal) structure of correctly formed dilated intestinal blood vessels.

Malformation is any deviation from normal physical development, a developmental anomaly resulting in gross structural and functional changes in an organ or tissue. A malformation can be a congenital or acquired developmental defect, and can also result from a disease or trauma.

Klippel-Trenaunay syndrome is based on congenital obstruction of the deep major veins of the lower extremities, which clinically manifests as hypertrophy and dilation of subcutaneous veins with the appearance of pigmented spots covering extensive areas of the lower extremities, along with elongation and thickening of the limb due to hypertrophy of the skeleton and soft tissues. These symptoms can be expressed not only in the lower extremity but also on the corresponding buttock, half of the torso, face, and upper extremity.

Rendu-Osler disease is an inherited disorder based on vascular endothelial deficiency, resulting in the formation of multiple angiomas and telangiectasias (vascular anomalies) that bleed across various areas of the skin, the mucous membranes of the lips and mouth, and internal organs.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Intestinal angiodysplasias are a pathological condition characterized by a malformed (pathological) structure of the blood vessels in the intestinal wall [1, 2].

1.1.1 Congenital form of intestinal angiodysplasia

The congenital form of intestinal angiodysplasia is a vascular lesion localized in the gastrointestinal tract (most commonly in the rectum). Foreign literature uses the term vascular malformation. Such changes were first described in 1839 by B. Phillips, who reported three cases of massive bleeding from a walnut-sized tumor located in the rectum. Subsequent authors published information mostly on isolated cases of intestinal angiodysplasia [3].

1.1.2 Acquired form of intestinal angiodysplasia

By acquired angiodysplasia, we mean a disease caused by the acquired pathological (abnormal) structure of correctly formed dilated intestinal blood vessels. In literature, such changes are also referred to as: vascular anomalies, vascular ectasias, telangiectasias [4, 5].

Data from three large studies established that in the Eastern population, angioectasias are distributed almost equally between the proximal and

distal parts of the small intestine (44–69% and 31–56%, respectively) [6–8].

Conversely, in the United States of America (USA), the vast majority of lesions (93%) were localized in the jejunum and only 7% in the ileum [9, 10].

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

The congenital form of intestinal angiodysplasia is associated with impaired vessel formation in the intestinal wall during the intrauterine period [3].

There is no universal consensus regarding the causes of acquired angiodysplasia. Pathomorphological examination of these vascular disorders shows that they consist of dilated, congested vessels, mostly lined with endothelium and significantly less frequently with a small amount of smooth muscle. Subsequent obstruction of submucosal veins (functional venous insufficiency) due to smooth muscle spasm inevitably leads to their dilation over the years and, retrogradely, to capillary dilation. This is how acquired angiodysplasia develops. Mucosal ischemia exacerbates this condition [11].

1.3 Epidemiology of the Disease or Condition

Angiodysplasia is a rare disease. Experience from individual clinics ranges from 1 to several dozen observations over long follow-up periods, indicating a low prevalence of dysplasia. Epidemiological data on population prevalence are lacking. However, studies describe the proportion of angiodysplasias among the causes of gastrointestinal bleeding. Studies from the late 1980s showed that angiodysplasia accounted for 15–27% of lower GI bleeding cases [12–15]. More recent and larger studies have shown a lower proportion of angiodysplasias among lower GI bleeding causes. For instance, in a large study involving 1,112 patients with bleeding, the incidence of angiodysplasia was 4.76% from 1988 to 1997 and 2.3% from 1998 to 2006 [16]. Similar results of ~3% were obtained in another large study [17].

1.4 Features of Coding the Disease or Condition

Class XI: Diseases of the digestive system

Block: K55 Vascular disorders of intestine.

K55.2 Angiodysplasia of colon

K55.3 Angiodysplasia of small intestine

K55.8 Other vascular disorders of intestine

1.5 Classification of the disease or condition

Angiodysplasias are classified by origin, morphological structure, extent and localization of the lesion, as well as clinical course [4].

1.5.1 Classification by origin:

· Type I – congenital angiodysplasia:

o non-hereditary form;

o hereditary form (Rendu-Osler disease).

· Type II – acquired angiodysplasia.

1.5.2 Classification by morphological structure:

· Venous angiodysplasia:

o capillary type;

o cavernous type.

· Arteriovenous angiodysplasia.

· Arterial angiodysplasia.

1.5.3 Classification by prevalence:

· Localized angiodysplasia (involvement of a single colonic segment, not exceeding 5 cm in length).

· Diffuse angiodysplasia (involvement of one or more colonic segments exceeding 5–10 cm in length).

· Generalized angiodysplasia (systemic "angiomatosis" with concurrent involvement of other organs and systems, Klippel-Trenaunay syndrome).

1.5.4 Classification by localization:

· Colon.

· Small intestine.

· Mixed form involving both the colon and small intestine.

1.5.5 Classification by clinical course:

· Uncomplicated (including asymptomatic).

· Complicated.

1.6 Clinical presentation of the disease or condition

The main clinical manifestation of angiodysplasias is gastrointestinal bleeding. This may present with:

• varying degrees of blood mixed with stool;

• passage of blood from the anus;

• general weakness, dizziness, episodes of fainting.

In congenital angiodysplasia, a pathognomonic sign of such bleeding is its painless nature, occurring exclusively during defecation. The blood admixture is usually bright red due to the rectal localization of the lesion. Conversely, acquired angiodysplasia is more commonly characterized by a dark blood admixture in the stool, associated with involvement of the small intestine and the right colon. General weakness, dizziness, and fainting episodes may be caused by varying severity of anemia or absent in asymptomatic cases [4].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Criteria for establishing the diagnosis/condition - based on pathognomonic data:

1) clinical evaluation and medical history;

2) instrumental diagnostic methods.

Endoscopy is the primary diagnostic method for angiodysplasia. Every effort should be made to perform a maximally complete endoscopic examination of all GI tract segments.

Diagnosis of intestinal angiodyslasias involves the following objectives:

1. Determining the localization and extent of the pathological process;

2. Assessing hemodynamics, bleeding intensity, and volume of blood loss.

In the congenital form of intestinal angiodysplasia, the localization of the pathological process in the vast majority of cases is the rectum; the early onset of painless, persistent rectal bleeding, multiple prior surgeries on the distal rectum, and the possible presence of extraintestinal manifestations make the diagnosis of congenital colonic angiodysplasia straightforward. Digital rectal examination with proper interpretation of findings proves effective in 90% of patients. A striking specific endoscopic and radiological picture confirms the diagnosis and establishes the extent of the lesion.

Differential diagnosis of congenital angiodysplasias must be performed with conditions accompanied by bleeding from the stomach and small intestine [3, 4]:

· tumors of the colon and anal canal;

· diverticular disease of the colon complicated by bleeding;

· inflammatory bowel diseases (ulcerative colitis, Crohn's disease);

· hemorrhoidal disease.

Differential diagnosis of acquired angiodysplasias must be performed with conditions accompanied by bleeding from the stomach and small intestine [3, 4]:

· peptic ulcer disease of the stomach and duodenum;

· tumors of the stomach, duodenum, and small intestine;

· Meckel's diverticulum;

· inflammatory diseases affecting the small intestine.

2.1 Complaints and Anamnesis

The presence of angiodysplasia in a patient may be entirely asymptomatic. Changes may be discovered during screening colonoscopy when vascular malformations are located in the colon or the terminal ileum. Alternatively, the clinical presentation may be driven by lower gastrointestinal bleeding and can vary widely depending on the intensity and duration of the bleeding. The primary complaint is blood in the stool or a history of GI bleeding episodes. Orthostatic hypotension may occur rarely—during acute and massive bleeding. Abdominal pain is typically absent [3, 4].

In the medical history of congenital angiodysplasias, the onset of the first symptoms is typically observed in early childhood or from birth, often dominated by recurrent lower gastrointestinal bleeding and a tendency toward more massive blood loss with each subsequent bleeding episode.

Acquired angiodysplasias are characteristically diagnosed in older individuals (over 60 years of age), presenting with episodes of rectal bleeding of varying intensity that occur without apparent cause or following physical exertion against a background of satisfactory general well-being. Notably, according to some authors, up to 50% of patients with this pathology have undergone repeated emergency surgeries due to recurrent, severe gastrointestinal bleeding. However, intraoperative findings involving multiple gastrotomies, enterotomies, and colotomies failed to identify the source of hemorrhage. In some cases, unjustified resections of various intestinal segments were performed during these procedures. Researchers note that the rarity of identifying the bleeding source intraoperatively is another hallmark of acquired angiodysplasia [3, 4].

2.2 Physical Examination

Physical examination cannot establish the diagnosis of intestinal angiodysplasia because the pathological changes characteristic of the disease are localized within the intestinal lumen. A congenital form of intestinal angiodysplasia can be suspected during a digital rectal examination if an intraluminal mass of variable size, soft consistency, and easily compressible upon palpation is detected. It is worth noting that in almost half (54.2%) of patients with concurrent extraintestinal manifestations of systemic angiodermatosis and complaints of gastrointestinal bleeding, colon angiodysplasia could be diagnosed with a high degree of certainty upon external examination alone [4]. The presence of pigmented (vascular) spots, superficial varicose veins, and hypertrophy of the affected limb is known in the literature as Klippel-Trenaunay syndrome. This variant of the disease is also quite common (up to one-third of observations according to individual authors) [4, 18].

2.3 Laboratory Diagnostics

There are no specific laboratory tests for angiodysplasia. Laboratory methods are used to detect anemia and coagulopathy.

• All patients are recommended to undergo a complete blood count (CBC) and coagulopathy screening (coagulation profile assessment) to evaluate total blood hemoglobin levels, severity of anemia, and baseline coagulation disorders [3, 4]

Level of Evidence CQuality of Evidence 4Level of recommendation validity C (Level of evidence certainty - 4)

Comment. A common finding in both types of angiodysplasia in blood tests may be anemia of varying severity [3, 4].

Comment. A study by Holleran G. et al. (2015), which included 80 patients (40 in the study group and 40 in the control group), demonstrated for the first time a significant increase in the median angiopoietin-2 level in patients with small bowel angiodysplasia (3779.48 pg/mL) compared to the control group (2506.78 pg/mL) (p=0.003) [19].

2.4 Instrumental Diagnostics

2.4.1 Congenital angiodysplasia

2.4.1.1 Endoscopic Diagnostic Methods

• All patients with angiodysplasia are recommended to undergo colonoscopy to identify vascular malformations [3, 4].

Level of Evidence CQuality of Evidence 4Level of recommendation validity C (Level of evidence certainty - 4)

Comment. The high diagnostic resolution of colonoscopy makes it possible to determine the extent of the pathological process. The endoscopic presentation of congenital colon angiodysplasia is quite characteristic. Vascular formations protrude above the mucosal surface as uneven, nodular elevations and protrusions of various shapes and sizes filled with blood. They have a soft consistency, are easily compressible, and rapidly refill with blood. Their color is dark crimson, with a richer bluish tint than cutaneous lesions due to greater mucosal translucency. These formations may have a grapelike (nodular) appearance ranging from deep blue to bright red. Such a pronounced endoscopic picture is found in 58.3% of cases. In the remaining observations, the manifestation is less prominent with smaller vascular formations and a bluer color, but all characteristic symptoms are invariably present. Analysis of endoscopic findings revealed symptoms typical of congenital colon angiodysplasia: relative narrowing of the bowel lumen due to vascular formations, flattening and collapsing during air insufflation, absence of mucosal ulceration, and a clear demarcation between the affected segments and normal colon. Colonoscopy establishes the extent of the pathological process [3, 4].

2.4.1.2 Radiological Diagnostic Methods

• All patients with angiodysplasia are recommended to undergo contrast-enhanced magnetic resonance imaging (MRI) of the retroperitoneal space and contrast-enhanced computed tomography (CT) of the abdominal organs [20–22].

Level of Evidence CQuality of Evidence 4Level of recommendation validity C (Level of evidence certainty - 4)

Comment. MRI is an effective method for diagnosing congenital intestinal angiodysplasia [20–22]. Thus, in a study by Wang T. et al. (2010), angiodysplasia was diagnosed using MRI in 9 patients [21]. Characteristic manifestations of the disease include irregular thickening of the rectal wall, tortuous vascular pathways, and lumen dilation [20, 21]. CT is also an effective method for diagnosing congenital intestinal angiodysplasia [21, 23]. CT signs of intestinal angiodysplasia may include thickening of the intestinal wall, tortuous vascular pathways, lumen dilation, and the presence of atypically located phleboliths of varying sizes, localized most frequently along the affected rectum and in the pararectal tissue [21]. However, the diagnostic value of this method is inferior to MRI [20, 21].

• All patients, if technically feasible, are recommended to undergo mesenteric angiography given its high sensitivity and specificity in assessing the nature and extent of the process [24–26].

Level of Evidence CQuality of Evidence 5Level of recommendation validity C (Level of evidence certainty - 5)

Comment. The sensitivity of the method reaches 86%, and specificity approaches 100% [24–26]. This method allows for the diagnosis of occult bleeding at a rate of 0.5 mL/min or more [27, 28]. Analysis of the obtained angiograms revealed characteristic signs: the presence of "contrast" spots in the projection of the lesion, prolonged contrast retention in the arterial bed (up to 15 seconds), delayed venous phase, early venous runoff, presence of arteriovenous shunts, and dilation of major arteries and veins. These symptoms are most frequently detected in patients with Klippel-Trenaunay syndrome. If angiography is positive, endovascular vascular embolization (A16.12.051) is considered a sufficiently effective hemostatic measure. Studies demonstrate good efficacy of the method in 60%–90% of observations. Bleeding recurrence occurs in 0–33% of cases. Clinically significant ischemia occurs in less than 7% of cases. However, these figures apply to all cases of bleeding from the small and large intestine, not just angiodysplastic ones [29, 30].

• Patients in whom a diagnosis has not been established by endoscopic examinations or mesenteric angiography are recommended to undergo radionuclide imaging to identify the source of gastrointestinal bleeding, provided it is technically feasible [28]

Level of Evidence CQuality of Evidence 4Level of recommendation validity C (Level of evidence certainty - 4)

Comment. The most sensitive method for diagnosing lower gastrointestinal bleeding is radionuclide scintigraphy (aortoarterioscintigraphy, phleboscintigraphy, etc.). Unlike endoscopic methods and mesenteric angiography, this technique does not involve a therapeutic intervention on the bleeding source. It does not require bowel preparation and can detect a bleeding source with a blood loss of less than 0.1 mL/min [28].

2.4.2 Acquired angiodysplasia

2.4.2.1 Endoscopic Methods

• All patients are recommended to undergo colonoscopy, and in the absence of changes in the colon, double-balloon enteroscopy for the purpose of establishing a diagnosis and determining the source of bleeding [3, 4, 31]

Level of Evidence BQuality of Evidence 1Level of recommendation validity B (Level of evidence certainty - 1)

Comment. During endoscopic examination, acquired angiodysplasia may appear as a round-shaped mucosal lesion, bright red or cherry-colored, not protruding into the intestinal lumen. Moderately dilated tortuous vessels 7–10 mm in length radiate from it. The size of these pathological lesions ranges from 0.3 to 0.7 cm. The lesions are easily traumatized, accompanied by droplets of blood. The small size of the vascular pathological lesion can also be considered a characteristic feature of acquired angiodysplasia. According to the largest study in our country, in the majority of patients, angiodysplasias are localized in the right colon and the terminal ileum, which is another characteristic feature of this disease [3, 4]. Double-balloon enteroscopy with examination of the entire small intestine is also a sufficiently informative study [10, 32, 33]. Thus, a meta-analysis by Brito H. et al. (2018), combining the results of 17 studies and including 1477 cases, reports a high diagnostic value of double-balloon enteroscopy in identifying the source of bleeding. The sensitivity of the method was 84%, and the specificity was 92%. The authors note that performing double-balloon enteroscopy after video capsule small bowel endoscopy increases the chances of detecting the source of bleeding by 7% [31].

• For patients in whom the diagnosis was not established during colonoscopy, provided there is technical capability to examine the small intestine, video capsule endoscopy of the small intestine is recommended [34]

GCR ALEL 1Grade of Recommendation A (Level of Evidence - 1)

Comment. Video capsule endoscopy is used to determine the source of obscure gastrointestinal bleeding. The method can be used when all other means of detecting the source of bleeding have been exhausted. The diagnostic value of video capsule small bowel endoscopy and double-balloon enteroscopy in determining the source of small bowel bleeding is 38–83% [35, 36] and 58% [37], respectively. The results of the latest meta-analysis confirm the obtained data [34]. In two independent studies, the opinion was expressed that video capsule endoscopy and double-balloon enteroscopy are complementary methods and can be used together to search for the source of small bowel bleeding [33, 38].

2.4.2.2 Radiological methods.

• All patients are recommended to undergo mesenteric angiography as an adjunct to endoscopic examination and if technically feasible [39].

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

Comment. Currently, two objective and complementary techniques can be considered effective diagnostic methods: mesenteric angiography and endoscopic examination (colonoscopy, enteroscopy) [3, 4]. At the same time, superselective mesenteric angiography is of decisive importance in diagnostics, as well as in choosing the method and extent of resection in patients with acquired intestinal angiodysplasia. The sensitivity of this method is 70%, and the specificity approaches 100% [39].

The main angiographic signs of acquired angiodysplasia are: dilatation of the main artery (ileocolic), opacification of the draining vein at an early stage of the study (at 3–4 seconds), the presence of clear and intense vascular plexuses in the intestinal wall, indicating the presence of arteriovenous shunts, and slow venous clearance [3, 4].

2.5 Other Procedures

Not required

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

The variety of causes of intestinal angiodysplasia requires the use of various types of treatment adequate for each form of the disease and for each specific clinical case [3, 4].

3.1 Treatment of congenital angiodysplasia

3.1.1 Minimally invasive treatment methods

• All patients with single, small vascular lesions, in the absence of severe bleeding, are recommended argon plasma coagulation of the bleeding vessel [3, 4, 40].

Level of Evidence CQuality of Evidence 4Level of recommendation validity C (Level of evidence certainty - 4)

Comment. In some situations, when there is mild anorectal malformation, argon plasma coagulation of the bleeding vessel can be used as a therapeutic measure with positive results [3, 4, 40].

There is evidence in the literature regarding the ineffectiveness of attempted local interventions on the bleeding vessel. Sclerotherapy and ligation have often led to recurrent gastrointestinal bleeding, which was most likely associated with both the technique and the nature of the sclerosing agent [18].

3.1.2 Surgical treatment.

In case of ineffectiveness of minimally invasive treatment methods, as well as the presence in the patient of congenital angiodysplasia with a large spread area, involvement of several segments of the colon, daily persistent rectal bleeding with a daily average blood loss of 30–50 ml or more, leading to severe and persistent anemia, significant homeostasis disorders, and deterioration of the general condition, resection of the affected intestinal segment is recommended [3, 4].

GCR CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comment. Most authors recognize surgery aimed at the resection of the affected segment as the only method of radical cure for patients with congenital angiodysplasia [3, 4]. In the vast majority of cases, the operation of choice is abdominoperineal resection of the rectum.

Surgical interventions undertaken in patients with congenital angiodysplasia of the colon are associated with significant difficulties, primarily due to the spread of the pathological process to adjacent organs and tissues in the pelvic cavity, the vascular nature of the lesion, and technical difficulties in achieving hemostasis. Thus, the affected intestinal wall is often completely covered with tortuous and dilated vessels merging into large cavernous conglomerates, and is frequently presented as a single "vascular tumor". In such variants, the mesentery and surrounding adipose tissue are affected, significantly increasing the size of the affected organ. Mobilization and removal of such a rectum, sometimes reaching 20 cm or more in diameter and occupying almost the entire pelvic cavity, presents significant technical difficulties. Cavernous vascular formations are so thin-walled that the slightest trauma causes poorly controlled bleeding [3, 4]. Another important feature that must be taken into account when performing surgery for this disease is the combined "involvement" of the anterior wall of the rectum and the posterior wall of the vagina. In such situations, it is necessary to know that pathologically altered vessels do not exhibit invasive growth, but rather there is a mutual interweaving of vascular conglomerates of the affected organs along a tortuous trajectory. Injury to adjacent organs at this stage of the operation (the prostate gland in men and the vagina in women) can lead to hard-to-stop bleeding from them.

The principles of mobilization and resection of the rectum in various diseases are quite widely known, but in patients with congenital angiodysplasia they become paramount due to the technical features determined during the operation and inherent only to this category of patients.

The basic rules when performing surgical procedures in patients with congenital angiodysplasia of the colon are: adherence to the fascial envelope principle during rectal mobilization, performed visually and sharply, careful handling of tissues, including those being removed, and minimizing their trauma, a sparing technique, and thorough hemostasis at all stages of the operation.

Thus, the most formidable and frequent intraoperative complication during rectal removal is hard-to-stop bleeding, which can be massive and pose an immediate threat to the patient's life [3, 4].

The aforementioned features and preoperative disorders determine the level of intraoperative blood loss. Thus, one study found that every fourth patient had a fairly pronounced degree of intraoperative blood loss (more than 30 ml/kg) [4].

If there are signs of fibrinolytic bleeding at the end of the operation and a blood loss level of more than 30 ml/kg of body weight, the operation must be completed by forming a single-barrel colostomy without attempting a pull-through of the proximal colon and with pelvic packing. These patients may undergo delayed pull-through of the colon into the anal canal within 6 to 12 months.

Some authors believe that patients with congenital angiodysplasia have a higher risk of thromboembolic complications. This is explained by the presence of a number of risk factors in these patients: a large number of varicose veins in Klippenstein-Trenaunay syndrome (often with symptoms of chronic phlebitis), pathological vascular formations in the pelvic cavity with sluggish blood flow, prolonged pelvic organ surgery, and a high incidence of presacral abscesses. The role of baseline coagulopathic disorders in these patients must also be taken into account. These patients also require evaluation for baseline coagulopathic disorders [3, 4].

Among late complications, attention should be drawn to the possible formation of a coloanal anastomosis stricture, the incidence of which reaches up to 18.6% according to literature data. One of the possible prerequisites for this may be pulling through the colon into the anal canal with redundancy. Therefore, preference should be given to operations with primary coloanal anastomosis formation and a diverting colo- or ileostomy. In the case of stricture formation and the inefficacy of repeated mechanical bougienage of the anastomosis, excision of scar tissue with the restoration of normal patency in the anastomotic zone is indicated [3, 4].

3.2 Treatment of acquired angiodysplasia

Management tactics for acquired intestinal angiodysplasias are determined by the volume of blood loss, frequency of bleeding, and the presence of positive angiographic signs.

3.2.1 Conservative Treatment

Currently, there is no specific drug therapy for intestinal angiodysplasia.

• All patients with acquired angiodysplasia are recommended injections of #octreotide** (ATC code: H01CB02) to reduce the rate of recurrent bleeding [43].

gC RLoE 2Grade of Recommendation B (Level of Evidence 2)

Comment. Octreotide** injections are administered at a dose of 20 mg once every 28 days, which significantly reduces the frequency of recurrent bleeding, the rate of repeated endoscopic interventions for hemostasis, and the frequency of blood transfusions.

There are a number of drugs aimed at reducing the risk of recurrent bleeding; however, the small sample size of patients, the lack of recommendations for the use of these drugs in intestinal angiodysplasia and optimal treatment regimens, and the high risk of adverse reactions do not allow for a reliable assessment of their efficacy in clinical practice [44, 45]. The use of the aforementioned drugs is possible under strict dynamic monitoring provided that:

· the source of bleeding cannot be identified endoscopically

· there is no profuse bleeding

· the patient has a severe somatic status and high risks of surgical complications

Other previously used hormonal drugs are currently not used to treat bleeding in intestinal angiodysplasia [46, 47]

3.2.2 Minimally invasive treatment methods

It should be noted that diagnostic double-balloon enteroscopy can be converted into a therapeutic procedure if deemed appropriate, for example, performing sclerotherapy. Indications for minimally invasive treatment methods: for minor intermittent gastrointestinal bleeding, endoscopic ablation, photocoagulation, or sclerotherapy is recommended [3, 4].

• All patients with acquired intestinal angiodysplasia, provided technical feasibility, are recommended endoscopic hemostasis methods (endoscopic arrest of bleeding using laser photocoagulation, endoscopic clipping of a bleeding vessel, endoscopic arrest of bleeding from a peripheral vessel using electrocoagulation, endoscopic arrest of bleeding using thermocoagulation, etc.) [3, 4, 48, 49].

Level of Evidence CQuality of Evidence 4Level of recommendation validity C (Level of evidence certainty - 4)

Comment. Thus, in one study, endoscopic ablation during enteroscopy was used in 23 patients. The technique was found to be highly effective, despite the need for repeat ablation in 30% of patients [48]. Fairly good results of endoscopic hemostasis can be achieved using neodymium laser photocoagulation, which, unlike argon laser, causes 3–4 times deeper and more extensive tissue fibrosis [50]. These data were confirmed by two independent studies [51, 52]. At the same time, the authors noted the need for cautious use of this technology in the small intestine. Another effective method of endoscopic hemostasis is argon plasma coagulation of the bleeding vessel. Thus, with a median patient follow-up of 18 months, the rate of rebleeding ranged from 11% to 19%, mainly due to the appearance of new bleeding foci [8, 49]. Despite the fact that various methods have been proposed to stop bleeding caused by intestinal angiodysplasia, they often recur after some time. This is the main reason for the difficulty in assessing the impact of applied techniques on any recurrent bleeding. In this regard, it is often recommended to combine medical and endoscopic therapy [3, 4]

3.2.3 Surgical Treatment

• In profuse recurrent intestinal bleeding with severe anemia and deterioration of the patients' general condition, and ineffectiveness of minimally invasive treatment, surgical treatment with resection of the affected bowel segment is recommended [3, 4].

Level of Evidence CQuality of Evidence 4Level of recommendation validity C (Level of evidence certainty - 4)

Comment. The operation of choice in most cases is right hemicolectomy with ileotransverse anastomosis. The use of laparoscopic technologies in performing the surgery significantly reduces invasiveness and ensures good immediate surgical outcomes [3, 4].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Specialized rehabilitation is not required; however, if an intestinal stoma is formed following surgical treatment, rehabilitation measures standard for stoma patients must be carried out [3, 4].

5. Prevention and Dispensary Observation

There are no preventive measures aimed at preventing the development of angiodysplasia.

6. Organization of Medical Care

Indications for hospital admission to a medical organization:

A patient diagnosed with intestinal angiodysplasia, in the event of needing surgical treatment and in the absence of disease complications, should be hospitalized in a general surgical inpatient facility electively.

A patient with intestinal bleeding, the possible cause of which is intestinal angiodysplasia, should be hospitalized in a general surgical inpatient facility.

Indications for patient discharge from a medical organization

1) Absence of surgical complications in the event of surgical treatment;

2) Exclusion of ongoing bleeding, absence of severe anemia.

7. Additional Information

Factors negatively affecting treatment outcomes:

1. Refusal of surgical treatment in case of ongoing bleeding;

2. Selection of treatment method in the absence of reliable data on the localization and nature of angiodysplasia.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

All 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 these clinical guidelines:

1. Coloproctologists

2. Surgeons

3. Gastroenterologists

4. Internists

5. General practitioners (family physicians)

6. Endoscopists

In these clinical guidelines, all data are ranked by level of reliability (evidence) depending on the quantity and quality of studies on the issue.

Table 1.Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

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

Table 3. Scale for grading grades of recommendation (GR) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

Clinical guidelines are updated every 3 years.

Appendix A3. Reference Materials

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

1. Article 76 of Federal Law of the Russian Federation No. 323-FZ dated November 21, 2011 (as amended on December 25, 2013) "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation", regarding the development and approval of clinical guidelines (treatment protocols) for the provision of medical care by medical professional non-profit organizations;

2. Order of the Ministry of Health and Social Development 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 Coloproctological Diseases of the Colon, Anal Canal, and Perineum";

3. Order of the Russian Ministry of Health No. 203n dated May 10, 2017 "On Approval of Criteria for Assessing the Quality of Medical Care"

4. Order of the Russian Ministry of Health No. 72n dated February 11, 2022 "On Approval of the Standard of Medical Care for Adults with Intestinal Angiodysplasia (Diagnostics and Treatment)"

Appendix B. Physician Action Algorithms

Management algorithm for a patient with congenital intestinal angiodysplasia

Management algorithm for a patient with acquired intestinal angiodysplasia

Appendix C. Patient Information

Intestinal angiodysplasia is a rare disease associated with vascular pathology of the intestinal wall. Gastrointestinal bleeding may be the sole clinical manifestation of the disease. Delayed diagnosis due to late presentation to a physician poses a life-threatening risk due to the development of severe anemia. Treatment is surgical in most cases and involves intestinal resection. With timely diagnosis and treatment, complete recovery is possible.

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

No.