Colon and Rectal Polyps: Clinical Guidelines

List of Abbreviations

NOS – not otherwise specified

IBD – inflammatory bowel disease

VCE – video capsule endoscopy

VCS – videocolonoscopy

HB – hot biopsy

HP – hot polypectomy

BEN – benign epithelial neoplasm

GI – gastrointestinal tract

CRC – colorectal cancer

CT – computed tomography

MRI – magnetic resonance imaging

CP – clinical practice guidelines

CRC – colorectal

SEN – superficial epithelial lesion

PET – positron emission tomography

RCT – randomized controlled trial

EC – early cancer

SRS – sigmoidoscopy

APS – adenomatous polyposis syndrome

Level of Evidence (LoE) – level of certainty of evidence

Ultrasound – ultrasound examination

Grade of Recommendation (GoR) – level of recommendation persuasiveness

CB – cold biopsy

CP – cold polypectomy

ADR – adenoma detection rate

ESD – endoscopic submucosal dissection

EMR – endoscopic mucosal resection

ASA (American Society of Anesthesiologists) – American Society of Anesthesiologists

** – vital and essential drugs

# – off-label drug

Terms and Definitions

Cold forceps/snare biopsy – mechanical removal (without electrical current) of a biological tissue fragment using biopsy forceps or a polypectomy snare.

Hot forceps/snare biopsy – removal of a biological tissue fragment using biopsy forceps or a polypectomy snare with electrical current.

Neoplasm (synonyms: neoplasia, tumor) – a clone of cells differing from other tissues by autonomous growth and somatic mutations [1].

Intraepithelial neoplasia – a type of non-invasive epithelial tumor, a term replacing and defining adenoma and dysplasia in the consensus Vienna Classification of Gastrointestinal Epithelial Neoplasia [2].

Polyp (broad sense) is a collective term firmly established in everyday professional speech as a short, practical term denoting virtually any intraluminal neoplasm. The collective term "polyp" is predominantly used to denote benign epithelial neoplasms, but it is also used to denote lesions of other origins (inflammatory, hamartomatous, subepithelial/submucosal), mainly when the true nature and origin of the lesion remain unclear/unknown for the time being. This definition duality is reflected in the disease coding according to the International Statistical Classification of Diseases. Specifically, in ICD-10, it is coded in both Chapter II – "Neoplasms" and Chapter XI – "Diseases of the digestive system". After non-polypoid – flat (0-II type) and depressed (0-III type) superficial epithelial lesions were categorized separately at the Paris workshop in 2002, it became evident that it is advisable to distinguish the term "polyp" in its broad (described above) and narrow sense.

Polyp (narrow sense), as a synonym for a protruding SEN (0-I type) – a term denoting an epithelial neoplasm whose height exceeds half its diameter (criterion for diminutive lesions), or protruding into the organ lumen by more than 2.5 millimeters (the diameter of closed biopsy forceps cups), attached to the bowel wall by a stalk or broad base.

Malignant polyp – a polypoid epithelial neoplasm with proven presence of cancer cells within its structure. Unlike the term "polypoid carcinoma", the term "malignant polyp" emphasizes the specialist's confidence that they are dealing with a malignant tumor originating from a benign polyp, part of which still retains benign architecture.

Early cancer – a cancerous tumor confined to the mucosa or submucosa, regardless of the presence or absence of regional lymph node metastases.

Subepithelial lesion – a collective, primarily endoscopic term describing both neoplastic and non-neoplastic focal mass lesions of the large intestine originating from any layer of the organ wall except the epithelium. The term "subepithelial lesion/tumor" is gradually replacing the term "submucosal lesion/tumor", more accurately reflecting lesion morphology, as some of them—such as leiomyomas originating from the muscularis mucosae or neuroendocrine tumors originating from the deep glands of the mucosa—are strictly speaking intramucosal, although they appear "submucosal" upon endoscopic examination.

Cold polypectomy – mechanical removal (without electrical current) of an epithelial neoplasm using a polypectomy snare or biopsy forceps.

Hot polypectomy – removal of an epithelial neoplasm using a polypectomy snare or biopsy forceps with electrical current.

Endoscopic submucosal dissection (ESD) – a type of intraluminal endoscopic tumor resection where the mucosal and submucosal dissection is performed through the endoscope using specially designed electrosurgical knives under direct visual control.

Endoscopic mucosal resection (EMR) – a term denoting the endoscopic excision (typically with a polypectomy snare) of a mucosal fragment containing a neoplasm within unaffected tissue margins. In its classic variant, the term is used to denote the endoscopic removal of non-polypoid SENs following fluid injection into the submucosal layer.

Epithelial neoplasm – a benign or malignant neoplasm originating from the organ mucosal epithelium.

Superficial epithelial lesion (SEN) – an epithelial neoplasm whose depth of invasion is confined to the mucosal or submucosal layer, i.e., the two inner layers superficial to the GI lumen.

Polypoid (protruding) SEN (0-I type) – an epithelial neoplasm whose height exceeds half its diameter (criterion for diminutive lesions), or protruding into the organ lumen by more than 2.5 millimeters (the diameter of closed biopsy forceps cups), attached to the bowel wall by a stalk or broad base.

Non-polypoid SEN – an epithelial neoplasm whose height does not exceed half its diameter, or not protruding into the organ lumen by more than 2.5 millimeters (the diameter of closed biopsy forceps cups). These include flat (0-II type) and depressed (0-III type) neoplasias.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Since K63.5 (colonic polyp) and K62.1 (rectal polyp) designate not only benign epithelial neoplasms but also inflammatory, hamartomatous, and subepithelial lesions, these clinical practice guidelines (CPGs) have been developed for the diagnosis and treatment of benign epithelial neoplasms (BENs) of the colon and rectum (CR), which constitute a significant portion of the disease subclass grouped under ICD-10 code D12, specifically D12.0 – D12.8, as well as D37.4. These national clinical guidelines do not cover BENs of the anus and anal canal (code D12.9), hereditary polyposis syndromes, or non-epithelial neoplasms, as they exhibit distinct specificities in diagnosis, treatment, and prevention, and are addressed in separate CPGs.

SES of the GI tract, which include all types of serrated lesions, including hyperplastic polyps, sessile serrated polyps with or without dysplasia, traditional serrated adenomas, and adenomatous-like epithelial neoplasms, belong to the group of "superficial" epithelial neoplasms (SENs) [1-5]. At an authoritative global workshop in Paris in 2002, the aforementioned lesions were classified as tumors whose depth of invasion is limited to the mucosa or submucosa, i.e., the two inner layers superficial to the intestinal lumen. It is important to emphasize that early colorectal cancers (CRCs) were included in the SES of the GI tract group. This decision was made unanimously because the differential diagnosis between SESs and early CRC during colonoscopy is a challenging task. Tactical and methodological approaches to the treatment of both conditions largely overlap, which is due to the fact that the majority of SESs of the GI tract, including a significant proportion of early CRCs, can be radically resected using intraluminal endoscopic surgery techniques. Experts note that successful and definitive confirmation of these diseases is possible only after receiving the results of pathomorphological examination of the resected tumor. Thus, the choice of treatment method plays a significant role in improving patient outcomes and quality of life [3].

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

The development of SESs of the GI tract is based on a combination of exogenous and endogenous factors. To date, the role of external impacts—including environmental influences, low physical activity, dietary habits, national diets, as well as the composition of consumed food (foods high in fat and protein and low in fiber), smoking, and regular alcohol consumption—in the development of colonic SENs has been proven.

Endogenous factors:

– Age. A large number of studies demonstrate that the prevalence of colonic and rectal adenomas predictably increases by 10–15% in individuals aged 50 to 75 years [6-8]. Benign neoplasms of the colon and rectum in children are more common in the first decade of life, with the peak incidence occurring between the ages of two and five years [9, 10];

– Gender. In men, the detection rate of adenomatous colorectal neoplasms during screening colonoscopy is 1.77 times higher than in women [8]. In addition, large epithelial colorectal neoplasms (> 9 mm) are 50% more frequently observed in the male population compared to the female population [11]. In the structure of morbidity in men, CRC accounts for 10.9%, and mortality accounts for 9%. In women, morbidity and mortality are identical at 9.5% each [12];

– Heredity. A link between SENs and a family history is observed [13, 14]. Patients who have a first-degree relative with confirmed CRC have an increased risk of developing colonic polyps, as well as a higher risk of "advanced" adenomas [15, 16]. The detection rate of CRC increases by 1.76 times in patients who have a first-degree relative diagnosed with CRC, even after the age of 80 [17]. Hereditary genetic pathogenic variants are the main etiological factor in the formation of SENs in familial adenomatous polyposis of the colon (mutation in the APC gene) and MutYH-associated polyposis (mutations in the MutYH gene) [18]. Compared to adults, CRC in children is extremely rare. Hereditary cancer predisposition syndromes (ICPS)—a group of conditions in which patients are predisposed to a wide range of tumors as a result of germline pathogenic mutations—are an important cause of CRC in children [19];

– Inflammatory bowel disease (IBD). Patients with IBD (ulcerative colitis [UC] and Crohn's disease [CD]) involving at least 30% of the colon are at a higher risk of CRC than the general population [20].

The pathogenesis of colonic superficial epithelial neoplasms has not been fully investigated. However, the main pathways of colorectal cancer carcinogenesis are currently known. The traditional model involves sequential chromosomal instability, which accounts for 70–90% of cases, accompanied by progression from adenoma to carcinoma. At the same time, the serrated neoplasia pathway, accounting for approximately 10% of cases, is frequently associated with BRAF and KRAS oncogene mutations, whereas APC gene mutations are significantly less common [21-27]. In addition, about 8% of all CRC cases are associated with hereditary and familial forms of the disease, such as familial adenomatous polyposis and Lynch syndrome. Finally, about 2% of cases develop against the background of prolonged mucosal inflammation in inflammatory bowel disease, which is termed colitis-associated CRC [28-33].

1.3 Epidemiology of the Disease or Condition

The prevalence of colorectal epithelial neoplasms ranges from 20% at age 45 to over 50%–60% by age 85 [34-39]. The prevalence of colonic polyps in children and adolescents ranges from 0.08% to 6% [40, 41].

Based on screening colonoscopy results, it has been determined that polyps are detected in 20%–53% of individuals aged 50 years and older, among which up to 9.7% are "advanced" tumors defined as adenomas measuring ≥ 10 mm, or having a villous structure, or high-grade epithelial dysplasia [42-47]. According to a meta-analysis of publications including data on colonoscopy results in individuals aged ≥ 50 years, polyps were detected in 24% of observations, and the prevalence of "advanced" adenoma is about 4.5% [48]. It should be noted that the frequency of adenomas is higher among men and increases with age [48, 49].

1.4 Features of Coding the Disease or Condition

1.5 Classification of the disease or condition

Depending on the size, colorectal SENs are classified into [50-52]:

− Diminutive: up to 5 mm inclusive;

− Small: 6–9 mm;

− Intermediate (synonyms: medium-sized): 10–19 mm;

− Large: 20–39 mm;

− Giant: 40 mm and more.

*Adenomas measuring 10 mm and more and/or adenomas containing at least 20–25% villous component and/or high-grade (severe) intraepithelial dysplasia are classified as "advanced adenomas" [53].

According to the modified Borrmann macroscopic classification of epithelial tumors proposed by him back in 1926 to describe the appearance and growth pattern of advanced malignant tumors (types 1–4), superficial epithelial neoplasms belong to type 0. The term "type 0" was introduced to distinguish "superficial" polypoid and non-polypoid epithelial tumors (both benign and malignant) from advanced ones [3, 54].

The Paris endoscopic classification of superficial epithelial neoplasms of the colon of 2002 serves for a more detailed and accurate macroscopic evaluation of SENs. It is used to characterize both benign epithelial tumors and their precursors, as well as malignant tumors classified as type 0 during endoscopic examination (Table 1). Thus, according to the appearance and growth pattern of SENs, protruding (polypoid) SENs—subtype 0-I, flat (non-polypoid and non-ulcerated) SENs—subtype 0-II, and ulcerated (ulcerative, undermined) SENs—subtype 0-III are distinguished [3, 55].

Table 1 Macroscopic endoscopic classification of superficial epithelial neoplasms (SENs) of the digestive tract (type 0)

In addition, there are mixed forms of SENs that exhibit features of two types, for example: depressed-elevated (0-IIc + IIa); elevated-depressed (0-IIa + IIc).

Laterally Spreading Tumors (LSTs) — a type of colonic tumors with a specific growth pattern spreading along the intestinal mucosa, allowing them to reach a giant size without a significant increase in height. The initial/minimum diameter of LSTs that allows them to be classified into this category of spreading tumors is 10 millimeters. Laterally spreading tumors are subdivided into LST-G (Granular) and LST-NG (Non-Granular), and each of them is further divided into subtypes. LST-G is subdivided into homogeneous (LST-G-H) and mixed nodular (LST-G-NM) subtypes; LST-NG is subdivided into flat elevated (LST-NG-FE) and pseudodepressed (LST-NG-PD) subtypes [4, 55, 56].

The International Endoscopic Classification NICE (NBI International Colorectal Endoscopic) for colorectal epithelial neoplasms (2009) is based on the evaluation of color, microvascular angioarchitecture, and surface pattern of colorectal epithelial neoplasms when examined under narrow-band imaging (NBI) without magnification [57, 58]. According to the NICE classification, colorectal epithelial neoplasms are categorized into 3 types corresponding to their predicted histopathological structure: type 1 – hyperplastic and sessile serrated polyps; type 2 – all adenomas, both low- and high-grade dysplasia, and carcinoma with minimal submucosal invasion; type 3 – carcinoma with deep invasion [59].

In 2018, a group of Japanese experts introduced a fourth category by dividing type 2 into two subgroups: 2A, including low-grade dysplasia, and 2B, high-grade dysplasia or early carcinoma [60].

Universal Endoscopic Classification of Colorectal Tumors Using Magnifying Narrow-Band Imaging: The JNET classification by the Japanese NBI Expert Team. According to the JNET classification, colorectal epithelial neoplasms are divided into 4 types according to their predicted histopathological structure: type 1 – hyperplastic polyps / sessile serrated lesions; type 2A – low-grade intramucosal neoplasia; type 2B – high-grade intramucosal neoplasia / carcinoma with superficial submucosal invasion; type 3 – carcinoma with deep invasion [61, 62].

WASP Classification (Workgroup Serrated Polyps And Polyposis) [63]. The WASP classification was developed for the differential diagnosis of sessile serrated lesions from hyperplastic polyps and conventional adenomas based on endoscopic criteria. In the first stage of differential diagnosis, the NICE classification is used to distinguish type 1 colorectal epithelial neoplasms (serrated/hyperplastic) from type 2 (adenomatous). In the second stage, these neoplasms are assessed for the presence or absence of endoscopic features specific to serrated lesions.

These include:

1) cloud-like surface;

2) indistinct border;

3) irregular shape;

4) "dark spots/dots" within the crypts (pit pattern type II-O according to T. Kimura).

Based on the combination of endoscopic features, a conclusion is made regarding the suspected morphological structure of the lesion [64-66].

Classification of Pit Pattern (Microrelief) of the Mucosa and Colorectal Epithelial Neoplasms by S. Kudo, 1994. This classification is used in high-resolution endoscopy with chromocolonoscopy and magnification. There are seven main types of pit patterns and several additional ones. Pit pattern types I and II are characteristic of non-neoplastic colonic lesions. For types III and IV, the probability of submucosal invasion reaches 4%, while for type V it reaches 41%. Types III_L, III_S, IV, V_i, and V_N suggest the presence of neoplasia progressing from low to high risk of malignant development, where type III_S may correspond to high-grade neoplasia and carcinoma; V_i – high-grade neoplasia and carcinoma confined to the mucosa and superficial submucosa; type V_N – adenocarcinoma with deep invasion. The risk of malignancy increases in the following sequence: III_L < III_S < IV [67].

World Health Organization (WHO) Classification of Tumours of the Colon and Rectum adopted and published in 2019. The WHO classification uses the morphological codes of the International Classification of Diseases for Oncology, third edition, second revision (ICD-O-3.2). Tumors are coded according to their pathomorphological characteristics: /0 – benign tumor; /1 – uncertain, borderline, or unspecified behavior; /2 – carcinoma "in situ" and grade III intraepithelial neoplasia; /3 – malignant tumors, primary site [68].

Benign epithelial tumors and their precursors

* Codes marked with an asterisk were approved by the IARC/WHO Committee for ICD-O at its meeting in April 2019.

The consensus international Vienna classification of gastrointestinal epithelial neoplasia was first published in 2000 [69]. The latest revision of the Vienna classification, including recommendations on management tactics, was published as a draft in 2002 [70], recommended for widespread use (Table 2), and (partially) adopted in the latest 2019 WHO Classification of Tumours of the Digestive System [2].

Table 2. Vienna classification of epithelial neoplasia of the digestive tract; revision [70] (Current version; approved in 2002)

*The choice of treatment depends on the overall size of the neoplasm; the depth of invasion assessed by imaging, endoscopy, and endoscopic ultrasound; and general factors such as the patient's age and severity of comorbidities.

Pathomorphological staging of malignant colorectal polyps according to R.C. Haggitt (1985) [71]. According to the R.C. Haggitt classification for polypoid malignant epithelial neoplasms on a stalk (Ip type), 5 levels of invasion are distinguished [71, 72]:

Level 0 – no invasion beyond the muscularis mucosae;

Level 1 – invasion through the muscularis mucosae into the submucosa, limited to the head of the polyp;

Level 2 – invasion into the submucosa reaching the neck of the polyp;

Level 3 – invasion into the submucosa extending into the stalk at any level down to the base;

Level 4 – invasion into the submucosa of the bowel wall below the level of the base of the stalk, regardless of the depth of this invasion.

For polypoid malignant epithelial neoplasms with a broad base (Is type), according to R.C. Haggitt, only 2 levels of cancer invasion are distinguished: level 0 and level 4. Thus, according to modern concepts, invasion levels 1–3 according to R.C. Haggitt correspond to T1sm1, while level 4 can correspond to both superficial (T1sm1) and deeper invasion (T1sm2) into the submucosa. The Haggitt classification was quite widely used prior to the Paris Workshop in 2002 and continues to be used for staging the depth of invasion in malignant pedunculated polyps (0-Ip type tumors), but it is inappropriate for evaluating sessile polypoid tumors (0-Is type).

Universal pathomorphological staging of invasion depth for early colorectal cancer (T1). Evaluating the depth of invasion of early broad-based colorectal cancer by dividing the submucosa into 3 sublayers of equal thickness according to S. Kudo, 1984 [73] or R. Kikuchi, 1995 [74] is only possible in pathomorphological specimens containing the entire submucosa and at least a portion of the muscularis propria of the colon, i.e., specimens obtained via transabdominal bowel segment resection or full-thickness endoscopic resection. For a full assessment of tumor invasion depth into the submucosa following endoscopic tumor resection, including submucosal dissection, it is not reliable to use these classifications. Therefore, for resected specimens obtained via endoscopic mucosal resection (EMR), a universal system for assessing submucosal invasion depth in absolute values (microns) was adopted in 2002 [3]. Submucosal invasion depth is conventionally divided into two levels: superficial (sm1) and deep (sm2), with the boundary between them located at a depth of 1000 µ (microns). This particular grading system is currently the most widely used in clinical practice and scientific research.

An auxiliary classification in the TNM system is the R-classification, which is designed to assess the completeness of tumor removal. It reflects the efficacy of the intervention performed, influences the choice of further therapeutic tactics, and serves as a significant prognostic factor [75].

The following R categories are distinguished:

RX – Presence of residual tumor cannot be assessed

R0 – No residual tumor

R1 – Microscopic residual tumor

R2 – Macroscopic residual tumor [76].

1.6 Clinical presentation of the disease or condition

In most cases, superficial epithelial neoplasms of the colon and rectum remain asymptomatic for a long time, and screening examinations are the only way to detect them. When colorectal epithelial neoplasms reach large sizes, non-specific clinical symptoms may appear, such as constipation or diarrhea (including mucus discharge), blood in the stool, and abdominal cramps and pain with a high degree of variability.

According to some scientific publications, the detection rate of colorectal polyps during colonoscopy in asymptomatic patients ranges from 18.2% to 46% [77, 78]. In a study by Xiaohua Long et al., diarrhea accounted for the predominant share of all symptoms at 54.2%. This is explained by the fact that the majority of epithelial colorectal neoplasms are adenomas which, when large, can secrete a large amount of mucus, causing secretory diarrhea. Furthermore, it was also noted that women are more commonly affected by constipation, whereas men typically complain of diarrhea or hematochezia [79].

In numerous studies on rectal bleeding, the authors emphasize that hematochezia, in particular, is a symptom of advanced colorectal adenoma. This clinical manifestation, characterized by the discharge of fresh blood from the rectum, may indicate marked vascularization and an increased bleeding tendency typical of large adenomas or malignant neoplasms [80-82].

2. Diagnostics, medical indications and contraindications for diagnostic methods

The criterion for establishing the diagnosis is the detection of a colorectal epithelial neoplasm by endoscopic examination or an alternative instrumental method of large bowel examination (CT colonography, ultrasound, MRI).

2.1 Complaints and Anamnesis

For adults – Recommendation grade – B (level of evidence – 3).

For children – Recommendation grade – C (level of evidence – 5).

Comments: the main reason for difficulties in the timely detection of colorectal epithelial neoplasms is the absence of early and reliable clinical manifestations of this disease in 46% of patients [84, 86]. According to a meta-analysis of population screening studies among patients undergoing colonoscopy, using questionnaire-based stratification to identify relatives with colorectal neoplasms in the family history, the adenoma detection rate (ADR) during colonoscopy was 33.3% [87].

At the same time, in pilot screening studies with a positive immunochemical fecal occult blood test, the adenoma detection rate during colonoscopy was 54.1%, and with a high risk level according to questionnaires, it was 67.3% [88, 91].

In children, the most frequent clinical manifestations are hematochezia and rectal bleeding [89]. Complaints of polypoid masses prolapsing through the anus, with episodes of strangulation and auto-amputation of the polyp followed by hemorrhage, are not uncommon [90].

2.2 Physical Examination

• Patients with colorectal epithelial neoplasms are recommended to undergo a thorough physical examination, including a digital rectal examination, to rule out concomitant anal canal pathology and diagnose space-occupying lesions in the abdominal cavity [92-95].

For adults – Recommendation grade – C (level of evidence – 5).

For children – Recommendation grade – B (level of evidence – 2).

Comments: palpation of the abdominal organs and digital rectal examination make it possible to suspect the presence of colonic and rectal neoplasms [92, 93]. However, reliable diagnosis requires the prescription of instrumental diagnostic methods such as colonoscopy, abdominal ultrasound (comprehensive), transrectal ultrasound of the rectum, contrast-enhanced computed tomography of the small intestine, and MRI [94, 95].

2.3 Laboratory Diagnostics

For adults – Recommendation grade – C (level of evidence – 4).

For children – Recommendation grade – C (level of evidence – 4).

Comments: risk factors such as male sex (RR = 1.64), hypertension (RR = 1.54), use of antithrombotic agents (RR = 4.04), neoplasm size greater than 10 mm (RR = 3.83), right-sided localization of the neoplasm (RR = 2.48), and mucosal resection technique for removal (RR = 2.99) are risk factors for postoperative bleeding [98, 99]. Thus, in patients on long-term antithrombotic therapy, monitoring of the coagulography panel, timely discontinuation of antithrombotic agents, or prescription of bridging therapy is necessary before endoscopic removal of the neoplasm [91].

2.4 Instrumental Diagnostics

Comments: performing a colonoscopy is indicated [100]:

1) Individuals belonging to risk groups:

− individuals with a positive family history of hereditary polyposis syndromes and colorectal cancer [101, 102];

− patients with familial adenomatous polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and serrated polyposis syndrome [103-108];

− patients with previously diagnosed epithelial neoplasms of the large intestine [109];

− patients with inflammatory bowel disease [109-111];

− patients who have undergone radiation and chemotherapy treatments for diseases of the colon or adjacent organs [112, 113].

2) Individuals with the following clinical manifestations, complaints, and symptoms [114, 115]:

− disorder of defecation (constipation, diarrhea, unstable stool);

− passing blood during defecation;

− pathological impurities in the stool (mucus, pus);

− anemia;

− discomfort and abdominal pain;

− weight loss.

3) Individuals with suspected/established diseases/pathological conditions of the colon based on laboratory and instrumental diagnostics:

− individuals with a positive result on a rapid immunochemical fecal occult blood test [116];

−  tumors of the distal colon detected during rectosigmoidoscopy [117];

−  colonic changes identified by diagnostic imaging and capsule colonoscopy [117];

− diseases of adjacent organs (endometriosis, pelvic tumors, retroperitoneal and abdominal tumors) [118].

• Routine colonoscopy for the diagnosis of benign epithelial neoplasms of the colon and rectum is not recommended in all cases where the risk of the procedure outweighs its diagnostic value, and the results do not affect the choice of the patient's management and treatment strategy at the time of the colonoscopy and decision-making [100].

GCR CLEL 5Grade of Recommendation — C (Level of Evidence — 5).

Comments: absolute contraindications to elective colonoscopy include: acute cerebrovascular accident; acute myocardial infarction; severe cardiovascular, pulmonary, and mixed failure (decompensation stage) observed in coronary artery disease, heart defects, massive pulmonary embolism; cardiac rhythm disorders (especially in unstable states), such as paroxysmal bradyarrhythmia, atrial fibrillation or paroxysms of atrial fibrillation, grouped ventricular extrasystoles in the form of bigeminy or trigeminy, severe degrees of atrioventricular block; dissecting aortic or cardiac aneurysm.

Absolute contraindications to elective colonoscopy also include: hyperacute (fulminant) forms of inflammatory bowel diseases (ulcerative colitis, Crohn's disease, ischemic colitis, radiation colitis); acute abdominal inflammatory infiltrates (including acute diverticulitis); suspected abdominal abscess, peritonitis.

Relative contraindications to colonoscopy include: acute inflammatory diseases of the anorectal zone (anal fissure, acute hemorrhoids, hemorrhoidal thrombosis, paraproctitis); early postoperative period (abdominal and pelvic surgery); severe hepatosplenomegaly; tense ascites; hydrothorax, hydropericardium; severe blood coagulation disorders; hemorrhagic vasculitis; pregnancy (especially the second and third trimesters).

• Before starting the endoscopic intervention, it is recommended to obtain the patient's written informed consent for the examination and treatment to confirm that the patient has received complete and understandable information about the medical intervention, including the goals, methods, risks, and alternatives, and voluntarily agrees to its performance [119].

GCR CLEL 5Grade of Recommendation — C (Level of Evidence — 5).

Comments: every patient must be explained in an understandable form both the positive aspects of the screening/diagnostic examination and endoscopic surgical intervention, and the associated risks. Information should include an explanation of the purpose of the intervention; preparation and procedure; discussion of possible discomfort, early and late complications; alternative methods of examination, as well as the advantages of colonoscopy compared to other methods. Before signing the informed consent form, the attending physician or other medical worker provides the patient or their legal representative with accessible and complete information about the goals, methods of medical care, associated risks, possible types of medical interventions, consequences of these interventions, including the likelihood of complications, and expected treatment outcomes. Informed consent is drawn up as an official document and signed by the patient or their legal representative. It is suggested to register the number of patients refusing colonoscopy on the day of the procedure and during the procedure, as well as the reasons for refusal.

For adults – Level of Evidence – B (Confidence Level of Data – 1).

For children – Recommendation grade – B (level of evidence – 2).

Comments: effective patient preparation for colonoscopy is a key factor in ensuring a high-quality examination [127, 137]. High-quality patient preparation ensures the possibility of cecal intubation, a detailed examination of the mucosa of all segments of the colon, and the detection of pathological changes, including neoplasms. In conditions of inadequate preparation, the detection of neoplasms is difficult or impossible [128]. Currently, there are many different regimens for preparing patients for endoscopic interventions on the colon. Difficulties in preparation occur in patients who have difficulty reading instructions; socially and economically disadvantaged individuals; elderly patients; hospitalized patients; immobilized patients; opioid users; and those with diabetes mellitus, chronic constipation, and a history of abdominal surgery [129].

• To ensure the effectiveness of diagnostic and therapeutic procedures during colonoscopy, as well as to minimize complications, it is recommended to assess the quality of bowel preparation using the Boston Bowel Preparation Scale (Appendix G1) and reflect the degree of bowel preparation in the endoscopic report/conclusion; this allows endoscopists to verify that the patient is properly prepared for the procedure, which in turn affects the accuracy of results and treatment safety [138-142].

LE CLoE 4Level of Evidence – C (Confidence Level of Data – 4).

Comments: The Boston scale is a repeatedly validated, convenient for daily practice, and widely used rating scale worldwide [139-142]. Its use ensures standardization in recording the quality of bowel preparation and examination during colonoscopy. According to the Boston scale, the quality of bowel preparation for colonoscopy can be considered adequate if the score is 6 or more, provided that each of the 3 evaluated segments scores at least 2 [141, 142].

• During colonoscopy, to distend the bowel lumen, it is recommended to use carbon dioxide (CO₂) [143, 144].

LE BLoE 1Level of Evidence – B (Confidence Level of Data – 1).

Comments: carbon dioxide does not support combustion and is absorbed from the bowel lumen into the blood 13 times faster than oxygen and 160 times faster than nitrogen. Therefore, its use in endoscopic interventions prevents explosions, uncontrolled emphysema, and pain associated with the procedure [144].

Comments: there is a correlation between the adenoma detection rate (ADR) and the withdrawal time of the colonoscope from the cecal dome to the anal verge. The adenoma detection rate (9.4% - 32.7%) depends on the withdrawal time (which ranges from 3.1 to 16.8 minutes). With a withdrawal time of more than 6 minutes, the ADR is statistically significantly higher than with a faster colon examination (28.3% vs. 11.8%, p < 0.001) [146, 147]. The optimal withdrawal time by an experienced specialist, excluding the performance of targeted visual diagnostics and biopsy, should be at least 10 minutes; the minimum allowable time is at least 6 minutes [148].

• To detect pathological changes, it is recommended to perform a detailed inspection of the terminal ileum and the entire colon as the colonoscope is withdrawn [149-151].

GCR CLEL 5Grade of Recommendation — C (Level of Evidence — 5).

Comments: the rotational technique of colonoscopy involves minimal gas insufflation during colonoscope insertion and, accordingly, does not require or provide adequate visualization of all parts and areas of the organ under study. A detailed examination of the colonic mucosa is performed during the withdrawal of the colonoscope from the ileum/cecum to the anal canal [151].

In the event that residual intestinal contents are identified in the intestinal lumen, it is strongly recommended to clean the surface of all examined mucosal areas by instilling fluid through the instrument channel of the endoscope or, if available, through a separate irrigation channel of the endoscope using a pump. If a significant amount of foamy contents is present, it is advisable to use an antifoaming agent solution (ATC group: A03Ax - other drugs for functional gastrointestinal disorders) [152-154].

• For colonoscopy and the detection of benign epithelial neoplasms of the colon, it is recommended to use high-resolution video endoscopes for multimodal examination and to improve image quality [155-170].

ACR BLEL 2Recommendation Readiness Level – B (Level of Evidence – 2).

Comments: Retrospective studies have demonstrated a significant increase in the adenoma detection rate (ADR) when examining patients with high-resolution colonoscopes. Thus, Buchner A.M. et al. reported an increase in the overall ADR during colon examination using high-definition equipment compared to standard colonoscopy from 24.3% to 28.8% (p = 0.012); the ADR for adenomas less than 5 mm in size when examined with high-definition colonoscopes increased from 16.9% to 19.9% (p = 0.024) [155]. Two retrospective cohort studies [156, 157] reported a significant increase in ADR in similar groups when performing high-resolution colonoscopy compared to standard colonoscopy by 8.2% (p = 0.02) and 12.6% (p = 0.007), respectively. A number of studies have demonstrated that the use of narrow-band imaging (NBI) does not lead to an increase in ADR, but allows for the detection of a significantly greater number of flat-type adenomas and adenomas located in the right colon [158-160].

The efficacy of narrow-band imaging (NBI) colonoscopy in the differential diagnosis of epithelial neoplasms, determining their borders, and performing targeted biopsy has been demonstrated in a number of studies [161, 162]. The use of the NBI mode during colonoscopy makes it possible to perform differential diagnosis of epithelial neoplasms according to the international NICE and JNET classifications (in NBI + magnification x 70 mode) [61, 163-165].

A study by Yoshida N. et al. showed that another digital contrast technology, LCI (Linked Color Imaging), improves the detection rates of colorectal neoplasms compared to white light modes [166]. Suzuki S. et al. published the results of a large multicenter randomized study, which demonstrated that LCI improves the adenoma detection rate compared to the white light mode (58.7% vs. 46.7%; P < 0.01) [167]. Other studies have demonstrated that the use of the BLI (blue laser imaging) mode, compared with white light examination, can improve the detectability of colorectal polyps, especially regarding their location, size, and morphology. The NICE and JNET classifications can be applied when using BLI for the endoscopic differential diagnosis of adenomas and hyperplastic polyps [168, 169].

A large cohort study involving 1936 patients established a higher ADR when using i-SCAN technology compared to standard white-light colonoscopy [170]. However, other studies showed no improvement in the adenoma detection rate. Currently, the role of i-SCAN in improving the adenoma detection rate has not yet been conclusively proven, and larger prospective studies are required.

• To increase the detection rate of adenomas, it is recommended to additionally use software (artificial intelligence) during colonoscopy, which has demonstrated a reproducible level of accuracy in the automated detection of benign epithelial neoplasms of the colon [171-175].

LE BLoE 1Level of Evidence – B (Confidence Level of Data – 1).

Comments: a systematic review analyzed 6 randomized controlled trials comparing colonsocopy with and without the use of a CADe system (2,480 individuals in the CADe group, 2,482 in the control group) [171]. The meta-analysis results showed a statistically significant increase in the adenoma detection rate when using computer-aided polyp detection systems, along with an increased colonoscope withdrawal time. Another systematic review and meta-analysis of seven randomized clinical trials (2,595 colonoscopies using CADe systems, 2,622 standard colonoscopies) demonstrated an 80% increase in the mean number of small adenomas detected per patient with computer-aided detection tools compared to standard colonoscopy [172]. However, the studies included in the review were predominantly conducted in a single country (PRC); furthermore, the skill level of the endoscopists performing the colonoscopies was not specified. A meta-analysis of six randomized controlled trials (4,996 cases) showed a higher detection rate for adenomas and polyps during colonoscopy using artificial intelligence regarding flat adenomas and sessile serrated lesions, although "standard" colonoscopy showed better results for pedunculated polyps [173]. A large multicenter randomized controlled trial (3,059 patients, 1,519 in the CADe-assisted colonoscopy group, 1,540 in the standard colonoscopy control group) demonstrated an increase in the adenoma detection rate among both endoscopists with an experience of over 5,000 performed colonoscopies and less experienced endoscopists [174]. Similar results were obtained in studies evaluating domestically developed systems [175].

Comments: studies have been conducted to evaluate the optimal number of biopsy specimens to increase the diagnostic accuracy of histological examination and reduce the workload for pathomorphologists. In one of these studies, including 37 cases of colorectal cancer, it was shown that taking 6 tumor fragments, compared to a smaller number, allows a statistically significant increase in the rate of histological confirmation from 61% to 92% (p < 0.02). The highest prognostic accuracy is achieved by performing a targeted biopsy of the central part of the tumor (96.1%) [177].

• To reduce the risk of colorectal cancer upon detection of a superficial epithelial neoplasm of the colon without signs of deep invasion, its removal with referral for histological examination is recommended [169, 178-180, 181].

GGR CLEL 4Grade of Recommendation – C (Level of Evidence – 4) – for adults.

GGR CLEL 5Grade of Recommendation – C (Level of Evidence – 5) – for children.

Comments: Colorectal superficial epithelial neoplasms (SENs) suspicious for malignancy require careful endoscopic evaluation with adequate irrigation and inspection of the entire lesion using a high-definition video endoscope equipped with virtual chromoendoscopy and magnification to identify areas of invasive growth. In diagnostically challenging cases, chromoendoscopy, contrast-enhanced examination of the gastrointestinal tract, and magnification are recommended to evaluate SENs according to S. Kudo's classification. For pit pattern type V without overt signs of deep invasion, en bloc resection of the SEN is suggested, followed by staging based on histological examination results. Preoperative biopsy data of a superficial epithelial neoplasm of the colon do not reliably rule out the presence of microfoci of adenocarcinoma. Studies on the biopsy of malignant colorectal neoplasms have shown that the false-negative rate can reach 18.5–86% [169]. According to Sung HY, in 39.8% of cases, there were discrepancies in morphological diagnoses between forceps biopsy and colonic polyp resection (the study included 996 polyps in 813 patients) [178]. Khalin K.D. et al. report that a focus of adenocarcinoma in a superficial epithelial neoplasm of the colon was detected upon preoperative biopsy in only 16.6% of cases [179]. Hah Y. et al. compared forceps biopsy with resection techniques. Factors reducing the diagnostic accuracy of biopsy included lesion size > 3 cm, presence of depression, and LST-mixed granular macroscopic type. The total number of morphological diagnosis discrepancies was 103 (57.5%) [180]. If, due to any medical, organizational, administrative, legal, or other circumstances, the removal of the SEN is delayed/postponed to a follow-up colonoscopy, it is recommended to indicate in the primary colonoscopy report that histological examination of the neoplasm will be performed after its removal during the recommended/scheduled repeat colonoscopy [182].

If en bloc removal of a colorectal neoplasm is impossible due to inadequate equipment and/or the endoscopist's lack of experience, representative images or video recording of the area suspected of invasion can be obtained (prior to deciding on a biopsy) and described in detail in the study report according to standard classifications. The patient must be referred to an expert center for consultation with a more experienced specialist or for a decision on further management. Endoscopic colonic biopsy remains a reserve option for colorectal neoplasms suspected of malignancy if en bloc resection and referral to a more experienced specialist are impossible [183-185].

Provided that en bloc removal of the neoplasm is not feasible, a qualified photo and video protocol of the entire lesion, performed using an expert-class colonoscope, is often of greater diagnostic value than an isolated biopsy [183]. If the colorectal neoplasm is indicated for endoscopic removal, a biopsy should not be performed because of the risk of submucosal fibrosis, which significantly complicates endoscopic resection. The incidence of fibrosis after biopsy reaches 77% [184]. Submucosal fibrosis develops within 3 weeks following the biopsy; therefore, if a biopsy has been performed, the question of further management should be addressed within this timeframe [185].

• To reduce the risk of contamination and dissemination of tumor cells, it is recommended that forceps and snares used for biopsy or removal of potentially malignant neoplasms in patients over 18 years of age not be reused during the current procedure, and tumor fragment sampling should be performed at the end of the examination [186].

LE CLoE 4Level of Evidence – C (Confidence Level of Data – 4).

Comments: the conducted study demonstrated that the working channel of the colonoscope during biopsy was "contaminated" with viable tumor cells, and that subsequent clean instruments introduced into the channel were contaminated with cells that were shown to retain their proliferative potential. Thus, although the probability of iatrogenic tumor cell transfer appears low, it may be the cause of metachronous CRC, which is potentially preventable and can be minimized by adhering to an oncologically safe order and sequence of using transchannel instruments during endoscopic interventions [186].

Comments: epithelial benign neoplasms and early colorectal cancer of the colon and rectum belong to the same group of superficial epithelial neoplasms [3, 70]. Making a reliable differential diagnosis between benign epithelial neoplasms and early colorectal cancer based on endoscopic examination results or even forceps biopsy is a non-trivial task. Therefore, it is recommended to remove both benign superficial epithelial neoplasms and neoplasms with suspected malignancy (but without signs of deep invasion) en bloc, which allows for a comprehensive morphological examination of the entire neoplasm and, consequently, a definitive differential diagnosis [1, 182].

Comments: according to a meta-analysis by S.E. Mason et al. [187], current methods of endoscopic examination and analysis of neoplasms are insufficient to ensure the safe application of the "resect and discard" strategy for neoplasms proximal to the rectosigmoid junction; all resected neoplasms must be submitted for pathomorphological examination of the surgical specimen. For precise evaluation of the horizontal and vertical resection margins, fixation of the lesions on a rigid, waterproof base is recommended [188-192]. Immediate fixation of the surgical specimen right after removal preserves the shape, size, and orientation of the neoplasm, allows for modeling the tumor's in vivo layout (including tumors removed in fragments), and prevents curling of the gross specimen during formalin fixation [188, 193]. In addition, excessive stretching of the specimen should be avoided to prevent distortion and damage to the layers [188, 194]. To prevent drying and potential deformation of the specimen when immediate fixation and immersion in formalin are not possible, it is permissible to moisten the resected tumor with normal saline** or cover it with a moist gauze pad. Circular tumors removed en bloc may be placed on a cylindrical object of suitable diameter (syringe, etc.) for better fixation.

• During the endoscopic removal of superficial epithelial neoplasms of the colon without submucosal invasion in adult patients, it is recommended to consider their removal radical if the resection margins are negative (vertical – Rv – and horizontal – Rh) in order to subsequently determine appropriate follow-up intervals [195-197].

LE CLoE 4Level of Evidence – C (Confidence Level of Data – 4).

Comments: endoscopic removal of superficial epithelial neoplasms is considered radical when the tumor is excised within healthy tissue (R0). Meta-analysis has demonstrated that risk factors for local recurrence include large size, piecemeal resection of neoplasms, and the presence of residual tumor at the resection margins (Rv1 or Rh1) [197]. When reliable evaluation of the resection margin is impossible (piecemeal resection, pronounced coagulation artifact at the margins from electrosurgical excision) (Rx), such patients should be categorized as having a persistent risk of neoplasm recurrence, and their follow-up interval should be shortened [197, 198].

2.5 Other Procedures

• Proctoscopy and sigmoidoscopy are not recommended as a standalone screening method for superficial epithelial neoplasms of the colon. Proctoscopy and sigmoidoscopy are suggested for detailed examination of the anal canal and excluded rectum area [199-202].

GCR CLEL 5Grade of Recommendation — C (Level of Evidence — 5).

Comments: flexible sigmoidoscopy allows examination of the inner surface of the colon up to 60 cm from the anal opening, while rigid sigmoidoscopy (proctosigmoidoscopy) examines up to 20–25 cm. These methods can certainly detect epithelial neoplasms of the left colon and rectum; they are also used to remove epithelial neoplasms or obtain tissue samples for vital pathomorphological examination of biopsy (surgical) material [199, 200]. Relative advantages of proctosigmoidoscopy and sigmoidoscopy include less time required for the procedures, a negligible rate of complications when the examination is not accompanied by polypectomy, and generally no need for sedatives. However, an obvious disadvantage of these methods is the inability to examine a significant portion of the colon, making their use as a standalone screening/diagnostic method for colonic epithelial neoplasms less and less significant. This is also due to the growing understanding of the serrated pathway of carcinogenesis, predominantly in the right colon, and the development of endoscopic equipment and colonoscopy techniques. Indeed, while the specificity of proctosigmoidoscopy and sigmoidoscopy for diagnosing neoplasms of the left colon is very high (98–100%), their sensitivity for the entire colon is unacceptably low, ranging from 35% to 70% for sigmoidoscopy and 10–20% for proctosigmoidoscopy [201, 202].

• For diagnostic purposes, colon capsule endoscopy (CCE) is recommended as a complementary, independent, or alternative endoscopic examination method in patients with contraindications to flexible colonoscopy, with incomplete flexible colonoscopy, or in patients refusing flexible colonoscopy [203–209].

For adults – Recommendation grade B (evidence level 2).

For children – Recommendation grade C (evidence level 5).

Comments: in the absence of tumor obstruction, TEV can be considered as an alternative to CT colonoscopy for examining the proximal colon in incomplete colonoscopy. The literature has reported the results of seven studies using TEV. In 75–100% of cases, TEV successfully visualized colon segments not reached during colonoscopy [203-206], while mucosal changes were detected in 24% to 100% of cases. Spada et al. compared computed tomographic colonoscopy and TEV in patients with incomplete colonoscopy [207]. In this study, TEV detected polyps ≥ 6 mm in 24.5% of patients (95% CI 16.6–34.4%), compared to 12.2% (95% CI 6.8–20.8%) with CT colonoscopy, yielding a relative sensitivity of 2.0 (95% CI 1.34–2.98), which indicated a higher sensitivity of TEV for diagnosing lesions ≥ 6 mm. Analysis of the diagnosis of larger epithelial lesions showed that TEV detected lesions ≥ 10 mm in diameter in 5.1% of patients (95% CI 1.9–12.1%), versus CT colonoscopy in 3.1% of patients (95% CI 0.8–9.3%), with a relative sensitivity of 1.67 (95% CI 0.69–4.00). The sensitivity of TEV for detecting polyps > 9 mm ranges from 87% to 92.8%, with a specificity of approximately 92% [208, 209].

• For screening/diagnosis of colonic epithelial neoplasms, it is recommended to use computed tomographic colonography as an independent/alternative method in patients with contraindications to colonoscopy, in patients refusing it, or in cases of incomplete colonoscopy [207, 210–214].

For adults – Recommendation grade B (evidence level 2).

For children – Recommendation grade C (evidence level 5).

Comments: computed tomographic colonography is the method of choice among all imaging techniques for diagnosing colonic epithelial neoplasms. The diagnostic accuracy for colorectal cancer and large/advanced epithelial lesions is similar to optical colonoscopy in both symptomatic and asymptomatic patients, and significantly exceeds the diagnostic accuracy of barium enema [207, 211, 213]. In a Japanese multicenter study involving 1,177 patients, the sensitivity and specificity of computed tomographic colonography for detecting colonic lesions > 9 mm in size reached over 90% [210], but this method is significantly inferior to colonoscopy and colon capsule endoscopy in detecting flat epithelial neoplasms smaller than 10 mm [210]. A major obstacle to using computed tomographic colonography in high-risk patient screening is that flat lesions in the colon may be missed, as well as the increasing radiation burden on the patient during repeated examinations [212, 213].

• For the diagnosis and detection of colonic neoplasms, it is recommended to use double-contrast barium enema as a complementary examination method in situations where a segment of the colon cannot be visualized endoscopically or using computed tomographic colonography [215–217].

For adults – Recommendation grade – C (level of evidence – 4).

For children – Recommendation grade – C (level of evidence – 5).

Comments: double-contrast barium enema allows examination of the entire colon and can detect up to 50% of large ENLs, but its sensitivity and specificity are significantly lower than those of colonoscopy and computed tomographic colonography [215]. Even in the presence of large ENLs, barium enema has a substantially lower sensitivity (48%) than colonoscopy; furthermore, it yields more false-positive results than colonoscopy [216, 217].

• Colorectal endosonography (Endo-US) and colorectal magnetic resonance imaging (MRI) are not recommended for routine clinical practice as standalone methods for characterizing benign epithelial neoplasms of the colon in patients over 18 years of age [218-223].

GCR BLEL 1Grade of Recommendation – B (Level of Evidence – 1).

Comments: to differentiate between benign and malignant colorectal ENLs, assess the depth of invasion, and determine the optimal removal method for neoplasms, it is recommended to rely primarily on the macroscopic type of the neoplasm, its surface microstructure, and localization, rather than on Endo-US and MRI data. A multicenter randomized controlled trial comparing magnifying chromoendoscopy with Endo-US in staging early colorectal cancer revealed no superiority of Endo-US, with an overall accuracy of 78% for both methods [218]. Four meta-analyses comparing the results of Endo-US, CT, and MRI in assessing T and N status of newly detected rectal neoplasms potentially eligible for endoscopic resection found no significant differences among these methods [219-222]. The accuracy of both Endo-US and MRI in distinguishing T1 from T2 stage was severely limited, accompanied by a high risk of overstaging the tumor process. In cases of discrepancy in tumor T-staging results between optical chromoendoscopy and Endo-US/MRI, the results of visual assessment during the endoscopic procedure should be considered a priority [223].

Endo-US and/or MRI may assist in assessing submucosal invasion of rectal ENLs if visual evaluation of the neoplasm raises suspicion of submucosal infiltration. Latest-generation ultrasonic endoscopic equipment allows for high-precision determination of anaplastic tissue thickness, confirming or ruling out tumor invasion into the submucosal and muscular layers of the bowel wall [223].

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

Conservative management of patients

• Conservative management, specifically surveillance without resection of benign epithelial neoplasms, is recommended for patients with the discovery of diminutive (1–5 mm) hyperplastic polyps of the rectum and rectosigmoid junction, typically multiple, provided that the hyperplastic nature of these polyps is determined with high reliability based on endoscopic examination using magnification combined with virtual chromoendoscopy [181, 224, 225, 226].

GGR CLEL 4Grade of Recommendation – C (Level of Evidence – 4) – for adults.

GGR CLEL 5Grade of Recommendation – C (Level of Evidence – 5) – for children.

Comments: hyperplastic polyps have an extremely low malignant potential (less than 0.6%) [198]. The vast majority of diminutive (≤ 5 mm) polyps of the rectum and rectosigmoid junction are precisely hyperplastic polyps [224, 225].

Endoscopic treatment of patients

Comments: the role of adenomas and serrated lesions in carcinogenesis, as well as the efficacy of their removal in interrupting the colorectal cancer sequence, has been proven in numerous studies [227-230].

Colonic epithelial neoplasms < 10 mm

For adults – Strength of recommendation – C (level of evidence – 1).

For children – Recommendation grade – C (level of evidence – 5).

Comments: CFB allows for the complete removal of an epithelial colonic neoplasm measuring ≤ 2 mm in 95.5–100% of cases [232-234, 237]. According to randomized studies, CFB is not inferior to "cold" snare polypectomy in the rate of complete resection and outperforms it in the retrieval rate of removed lesions [235, 236].

For adults – Recommendation grade B (evidence level 2).

For children – Recommendation grade C (evidence level 5).

Comments: in randomized studies, HB was significantly inferior to "cold" polypectomy in the rate of complete resection within healthy tissue and led to more pronounced thermal damage to the biopsy material [238-240]. Removal of epithelial colonic neoplasms ≤ 5 mm using the HB technique leads to the detection of residual tumor tissue in 10–17% of cases [241, 242].

For adults – Level of Evidence – B (Confidence Level of Data – 1).

For children – Recommendation grade – C (level of evidence – 5).

Comments: according to two meta-analyses including 12 studies (2,481 patients, 4,535 lesions) and 8 studies (1,665 patients, 3,195 lesions) comparing the results of "hot" polypectomy (HP) and "cold" polypectomy (CP), no significant difference was found in the rate of complete resection of neoplasms measuring < 10 mm within healthy tissue. Procedure duration, according to both meta-analyses, was significantly higher with HP [243, 244]. Although delayed bleeding occurred more frequently after "hot" than after CP, the difference did not reach statistical significance [244]. At the same time, a randomized study comparing CP and HP in patients receiving antithrombotic therapy showed a significantly lower risk of delayed bleeding in the cold polypectomy group [246].

Comments: CP leads to more superficial removal of epithelial colonic neoplasms compared to HP: the rate of muscularis mucosae presence in the specimen did not differ between the HP and CP groups, but submucosal tissue was more frequently detected in specimens after "hot" polypectomy [249]. According to a retrospective study comparing histological results of CP and EMR, the depth of resection in the histological specimen (from the muscularis mucosae level) in the CP and EMR groups was 76 and 338 µm, respectively (p < 0.001) [250]. The rate of neoplasms removed with positive or non-evaluable vertical resection margins was observed more frequently in the CP group than in the EMR group, at 6% and 1%, respectively (p < 0.05) [250].

Colonic epithelial neoplasms 10-19 mm

For adults – Recommendation grade B (evidence level 2).

For children – Strength of recommendation – C (level of evidence – 4).

Comments: EMR and HP have a similar rate of complete resection when removing epithelial neoplasms up to 14 mm in size [241, 252]. Submucosal injection of a solution reduces the risk of deep thermal injury to the intestinal wall.

Comments: piecemeal endoscopic removal of epithelial neoplasms of the colon is an independent risk factor for local recurrence [253]. According to a large multicenter study, the rate of local recurrence increased only when the lesion was removed in ³ or more fragments [254]. The time to recurrence also depended on the number of fragments: it was shortest (3.8 ± 1.9 months) when the tumor was removed in ⁵ or more fragments [253].

Comments: according to a meta-analysis, the use of more viscous solutions during EMR increases the likelihood of en-bloc resection and reduces the risk of incomplete tumor removal without affecting the development of complications [255].

Comments: according to two meta-analyses, prophylactic clipping of the mucosal defect to prevent delayed bleeding demonstrated no advantages either in the general group or for neoplasms > 20 mm in size [256, 257]. Prophylactic clipping leads to an increased procedure duration [258].

Colonic epithelial neoplasms > 20 mm

Comments: choosing the removal method (piecemeal EMR or ESD) based on the endoscopic evaluation of the tumor's morphological structure avoids the need for repeat surgical interventions in a number of patients [259]. Compared to EMR, ESD is associated with a higher rate of complete resection, as well as less involvement of lateral resection margins and recurrence, and has an advantage in the histological evaluation of the specimen [260].

Comments: according to a meta-analysis, for the removal of ≥ 20 mm neoplasms after piecemeal EMR, the local recurrence rate is 20% [266]. ESD increases the likelihood of complete neoplasm removal compared to EMR and reduces the risk of local recurrence; however, these benefits come at the cost of a higher risk of perforation and a longer procedure time. The potential need for surgical intervention for ESD complications is greater than for EMR complications [264, 267, 268].

According to one of the largest studies on EMR, the risk of local recurrence after piecemeal EMR is 16% and 4% at 4 and 16 months post-procedure, respectively, with the recurrence size being ≤ 5 mm in 71.7% of cases, and its endoscopic treatment being successful in 93.1% of cases [265]. Risk factors for local recurrence after piecemeal EMR included a neoplasm size > 40 mm, massive intraprocedural bleeding, and the presence of high-grade dysplasia / HGD [269].

• If a medical organization lacks sufficient experience in endoscopic removal of "complex" epithelial neoplasms of the colon (> 40 mm in size, occupying more than 2/3 of the bowel circumference, recurrent, lacking the "lifting sign"), it is recommended to refer adult patients to an expert-level facility [270-272].

LE CLoE 4Level of Evidence – C (Confidence Level of Data – 4).

Comments: EMR or ESD for the removal of complex colonic epithelial neoplasms, performed in specialized centers, are effective and relatively safe procedures [270, 272].

Comments: Several meta-analyses comparing TEM and ESD for the removal of large epithelial neoplasms and early rectal cancer have been published. The duration of ESD was significantly longer than that of TEM; other parameters, including the rate of complications, recurrences, and en bloc resection rates, showed no difference. The postoperative hospital stay was 1.6 times longer after TEM [275]. According to another meta-analysis, the procedure duration was shorter in the ESD group, while the length of hospitalization was shorter in the TEM group [276]. Thus, current data are insufficient to make an unequivocal choice in favor of one type of intervention over the other, and the choice currently depends on the experience of a specific clinic and its specialists.

Comments: BLACK EYE endoscopic marking at the sites of neoplasms suspected of malignancy, as well as detected early cancer, helps identify the resection site during follow-up colonoscopy or surgery. It is preferable to place more than one tattoo, typically 2–3 marks, on different walls of the bowel distal to the neoplasm and to document the injection details (material, volume, position relative to the neoplasms) in the procedure report in detail. Despite reports of potential complications following BLACK EYE endoscopic tattooing—such as fever, abdominal pain, and even abscess formation—it has been demonstrated that BLACK EYE administration following a preliminary submucosal injection of normal saline** is safe. BLACK EYE endoscopic marker for endoscopic tattooing based on sterile carbon microparticles has a superior safety profile [275].

Pedunculated epithelial neoplasms of the colon

Comments: HSP is the primary method for removing pedunculated polyps. The main type of complication when removing such neoplasms is delayed bleeding. Mechanical hemostasis techniques, such as endoscopic band ligation or clipping, reduce the risk of bleeding after the removal of pedunculated epithelial neoplasms [278, 279]. The greatest preventive effect against bleeding has been demonstrated in pedunculated neoplasms > 20 mm in size [280].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Specific rehabilitation measures for patients with benign neoplasms of the colon and rectum do not exist. Medical rehabilitation measures following endoscopic intervention are aimed, as after any surgical procedure, at the most rapid recovery in the postoperative period. However, they vary for patients after ESD, EMR, and cold snare polypectomy, and imply physical activity restrictions and dietary modifications for 7–14 days.

5. Prevention and Dispensary Observation

Prevention of colorectal epithelial neoplasms and reduction of colorectal cancer risk involve a multifaceted approach covering lifestyle modification, correction of harmful habits, and screening examinations. Prevention methods for colorectal epithelial neoplasms and colorectal cancer are divided into two categories: primary prevention methods aimed at identifying and correcting risk factors, and secondary prevention methods involving diagnostics (screening) and removal of colonic epithelial neoplasms.

Primary prevention of colorectal epithelial neoplasms and colorectal cancer involves adhering to a specific lifestyle, as well as eliminating risk factors for the development of colorectal epithelial neoplasms and colorectal cancer.

There is a correlation between a reduced risk of developing colorectal epithelial neoplasms and colorectal cancer, and dietary habits aimed at increasing the consumption of vegetables, fruits, whole grains, eliminating large amounts of red and processed meat and high-fat foods, as well as limiting alcohol intake [281-283].

Physical activity to maintain an optimal body weight and smoking cessation are also necessary for the prevention of colorectal epithelial neoplasms and colorectal cancer [281, 282].

Secondary prevention of colorectal epithelial neoplasms and colorectal cancer (screening) includes the diagnosis and removal of colonic epithelial neoplasms, which helps reduce the risk of developing colorectal cancer [284].

Comments: the advantages of the fecal occult blood test include: non-invasiveness, sensitivity to cancer and adenomas of 79% and 30%, respectively, and low cost [285, 286].

• In individuals over 18 years of age with a positive rapid fecal immunochemical occult blood test, it is recommended to perform screening or diagnostic colonoscopy with the detection and removal of all colorectal epithelial neoplasms [287].

GCR CLEL 5Grade of Recommendation — C (Level of Evidence — 5).

Comments: colonoscopy is the gold standard for colorectal cancer screening and serves as the primary diagnostic method, especially in individuals at high risk for colorectal cancer (hereditary syndromes, patients with a long-standing history of inflammatory bowel disease) [287].

Primary screening colonoscopy should be performed upon reaching the age of 40 (Order of the Russian Ministry of Health No. 404n dated April 27, 2021 (as amended on February 1, 2022) "On Approval of the Procedure for Preventive Medical Examination and Clinical Examination of Certain Groups of the Adult Population") [48]. In patients with first-degree relatives with colorectal cancer, screening colonoscopy should be performed at an age 10 years younger than the blood relative's age at the time of colorectal cancer diagnosis [288].

The surveillance intervals for patients who have undergone endoscopic electrosurgical removal of colonic epithelial neoplasms are determined by the morphological characteristics of these neoplasms, as well as the method of their removal [289].

Comments: patients at low risk for CRC (1–4 adenomas < 10 mm with low-grade dysplasia with/without villous components, or with any sessile serrated polyp less than 10 mm without dysplasia) are recommended to undergo repeat colonoscopy in 3 years [290, 291].

Follow-up colonoscopy in 1–2 years is recommended for patients at high risk for CRC: adenomas ≥ 10 mm with an adenoma count ≥ 5, serrated polyps ≥ 10 mm, as well as serrated polyps of any size with dysplasia [291].

If the first follow-up colonoscopy does not reveal polyps requiring surveillance, the next repeat colonoscopy is performed in 3 years. If polyps corresponding to a high risk for CRC are detected at the first follow-up colonoscopy, the next endoscopic procedure is performed in 1–2 years (Table 3) [292, 293].

Table 3 Intervals between repeat colonoscopies [290-297]

Comments: in case of fragmented resection of a polyp larger than 20 mm, it is necessary to perform an endoscopic check-up in 3–6 months, followed by a control colonoscopy in 1 year. This is due to the fact that fractional removal of ENLs is associated with a significant risk of tumor recurrence and the development of interval CRC [294-297].

6. Organization of Medical Care

Medical care for patients with benign colonic neoplasms, with the exception of medical care within the framework of clinical trials, in accordance with Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation" (as amended and supplemented), is organized and provided:

1) In accordance with the regulation on the organization of medical care by types of medical care, approved by the Russian Ministry of Health;

2) In accordance with Order of the Russian Ministry of Health No. 974n dated December 6, 2017, "On Approval of the Rules for Performing Endoscopic Examinations", Order of the Ministry of Health and Social Development of Russia No. 206n dated April 2, 2010, "On Approval of the Procedure for Providing Medical Care to the Population with Diseases of the Colon, Anal Canal, and Perineum in Coloproctology", Order of the Russian Ministry of Health No. 922n dated November 15, 2012, "On Approval of the Procedure for Providing Medical Care to the Adult Population in the Profile 'Surgery'", Order of the Russian Ministry of Health No. 116n dated February 19, 2021, "On Approval of the Procedure for Providing Medical Care to the Adult Population with Oncological Diseases", Order of the Russian Ministry of Health No. 560n dated June 9, 2020, "On Approval of the Rules for Performing X-ray Examinations", Order of the Russian Ministry of Health No. 557n dated June 8, 2020, "On Approval of the Rules for Performing Ultrasound Examinations", Order of the Russian Ministry of Health No. 464n dated May 18, 2021, "On Approval of the Rules for Performing Laboratory Tests";

3) Based on these clinical guidelines;

4) Taking into account the standards of medical care approved by the Russian Ministry of Health.

Referral for a diagnostic examination when a benign colonic neoplasm is suspected is carried out in accordance with Order of the Russian Ministry of Health No. 974n dated December 6, 2017, "On Approval of the Rules for Performing Endoscopic Examinations", after a preliminary assessment of the risks of the upcoming intervention.

Diagnostics of benign colonic neoplasms is carried out as part of primary specialized health care on an outpatient basis or in a day hospital setting, during sanatorium-resort treatment by an endoscopist and other medical specialists in an endoscopic room, which is a structural unit of a medical organization or other institution engaged in medical activities, or is part of the endoscopic department of a medical organization.

During diagnostic colonoscopy, total biopsy of PENs up to 10 mm in size can be performed using cold total snare biopsy or forceps biopsy. The recommended number of neoplasms to be subjected to total biopsy should not exceed 5 [298]. The complication rate when performing total biopsy by cold polypectomy [299] in an outpatient setting is: 0.07% – perforation, 0.14% – bleeding, 0.07% – submucosal hematoma [300], which is comparable to complications during diagnostic colonoscopy without additional interventions. Total biopsy in an outpatient setting using cold polypectomy [299] must be performed by an endoscopist in an endoscopic room, which is a structural unit of a medical organization or other institution engaged in medical activities, and is part of the endoscopic department of a medical organization. A prerequisite for the removal of neoplasms is the presence of adequate hardware and instrumental equipment in the endoscopy department for the endoscopic management of complications. It is recommended that all material obtained from endoscopic biopsy or endoscopic removal of neoplasms and sent for intravital morphological diagnosis be placed in a vial with a sufficient amount (at least 20 times the volume of the specimen) of a 10% neutral buffered formalin solution for no more than 24–48 hours (Order of the Ministry of Health of the Russian Federation No. 179n dated March 24, 2016, "On the Rules for Performing Pathological and Anatomical Examinations").

The rules for implementation, representative volume of biopsy material, rules (standard) for labeling, procedure for filling out the referral, procedure and deadlines for delivery to the pathology department, methodological support for histopathological examination (rules for fixation and staining of biomaterial, the need to perform and the nature of immunohistochemical examination) and other issues are systematically outlined in the rules for performing pathological and anatomical examinations (Order of the Ministry of Health of the Russian Federation No. 179n dated March 24, 2016, "On the Rules for Performing Pathological and Anatomical Examinations").

If a patient is found to have a benign colonic neoplasm requiring removal, coloproctologists, surgeons, and oncologists refer the patient for hospitalization to provide primary specialized health care or specialized medical care after a preliminary assessment of the risks of the upcoming intervention.

Treatment of patients with benign colonic neoplasms is carried out on a scheduled basis in the endoscopic department of a medical organization as part of primary specialized health care in a day hospital setting in the profiles "coloproctology", "oncology", "surgery", as well as within the framework of specialized medical care in these profiles in a day or 24-hour hospital setting.

The indication for hospitalization in a medical organization to provide primary specialized health care in a day hospital setting is the presence of a superficial epithelial neoplasm (PEN) of Is and/or II type less than 10 mm in size, in an amount of up to 10, the absence of recurrent benign neoplasms and signs of submucosal invasion in patients with grade I or II anesthetic risk according to the ASA scale (Appendix G). Removal methods – cold or hot polypectomy. Hospitalization is possible if the medical organization has a license to provide primary health care in a day hospital setting in anesthesiology and intensive care.

Indications for hospitalization in a medical organization to provide specialized medical care in a day hospital setting or short-stay hospital are: the size of pedunculated polyps (Ip): stalk diameter less than 10 mm, head size less than 20 mm; the size of PENs of Is and/or II type less than 20 mm; the absence of recurrent benign neoplasms and signs of submucosal invasion; the number of lesions up to 10; the degree of anesthetic risk according to the ASA scale – I or II. Removal methods – cold or hot polypectomy, as well as endoscopic mucosal resection. Hospitalization is possible if the medical organization has a license to provide primary health care in a day hospital setting or short-stay hospital in anesthesiology and intensive care.

Indications for hospitalization in a medical organization to provide specialized medical care in an inpatient setting (round-the-clock hospital) are: pedunculated polyps (Ip) with a diameter of more than 10 mm, a polyp head size of more than 20 mm, as well as Is and/or type II BENs and laterally spreading tumors larger than 20 mm. Hospitalization is also indicated if there are more than 10 neoplasms to be removed, suspected superficial invasion or recurrent nature of the neoplasm, as well as in patients with polyps of any size and an anesthetic risk of ASA class III or higher. High risk of their development, such as the risk of bleeding or perforation, are also indications for referral to a round-the-clock hospital. When a patient is in a round-the-clock hospital, there are no restrictions on the methods of endoscopic removal of BENs. Hospitalization is possible if the medical organization has a license to provide specialized medical care in an inpatient setting in anesthesiology and intensive care (Table 4).

Table 4 Organization of medical care for patients with epithelial neoplasms

7. Additional Information

• Potential adverse events and complications during colonoscopy and removal of colonic BENs.

One of the most important factors influencing the outcome of diagnosis and treatment/removal of superficial epithelial neoplasms of the colon are potential adverse events and complications. To record them and classify them by severity, it is proposed to use the new integrated "AGREE" classification [301] (Appendix G2). It is proposed to record all adverse events occurring both at the stage of preparation for colonoscopy (even if the planned colonoscopy was not performed), during the procedure, and for at least 30 days after it. When several adverse events occur during/after a single colonoscopy that are clearly related to each other, only the most serious adverse event should be classified [302].

Diagnostic errors (e.g., misinterpretation of chromoendoscopy or endoscopic ultrasound results) are not included in the "AGREE" classification of adverse events/complications in GI endoscopy and are considered separately.

• Bleeding during colonoscopy and removal of BENs.

Bleeding is the most frequent complication of colonic BEN removal, observed in 0.3% – 6.1% of patients. Most postoperative bleeding episodes develop within the first 7 days, but can also occur up to 14 days after surgery [303]. Intestinal bleeding, including severe bleeding, can also develop after biopsy and as a result of rough endoscopic manipulations during diagnostic colonoscopy [304]. The risk of bleeding depends on the patient's condition, the size and histological type of the lesion, its location in the bowel, and the removal method.

• Risk factors for bleeding associated with the patient's condition include: presence of cardiovascular diseases, in particular arterial hypertension; blood coagulation disorders, incl. as a result of taking nonsteroidal anti-inflammatory and antirheumatic drugs (NSAIDs), platelet aggregation inhibitors (ATC B01AC Platelet aggregation inhibitors, excluding heparin), and antithrombotic agents (Table 5).

• Risk factors associated with the nature of the neoplasm include: lesion size greater than 10 mm; stalk diameter greater than 5 mm; location in the right colon; malignancy and presence of inflammatory changes.

• Risk factors associated with the nature of the endoscopic surgical intervention include: endoscopic electrosurgical removal of a colonic neoplasm, especially EMR and ESD; use of cutting current only (risk factor for immediate bleeding) or exclusively coagulating current (risk factor for delayed bleeding); visible transected vessel in the base of the ulcer; marked coagulation damage in the ulcer base; hematoma and visible muscle fibers in the ulcer base. When removing lesions up to 10 mm by cold snare resection, intraoperative bleeding occurs with a frequency of up to 5.7%, the risk of delayed bleeding is 0% – 0.5%. When performing EMR for lesions larger than 20 mm, the bleeding risk is 5% – 7%. When removing large (up to 40 mm) adenomas, the bleeding risk increases to 8.9% of cases, and when removing giant ones (more than 40 mm) – up to 18.4% [305-310].

• The main method of instrumental diagnosis, arrest, and prevention of recurrent bleeding is emergency colonoscopy.

Endoscopic hemostasis can be performed: using hemostatic forceps in soft coagulation mode and/or by mechanical hemostasis using a single-use ligation device for the polyp stalk stump or clip appliers. Thermal hemostasis should be performed with great caution due to the risk of delayed perforation, especially in the right colon.

As an alternative method of hemostasis, irrigating hemostatic agents, powders (Hemoblock, EndoClot, etc.) can be used if available in the medical facility.

In case of ineffectiveness of endoscopic hemostasis, urgent surgical intervention is necessary. Management of delayed bleeding is outlined in Appendix B5.

Table 5. Recommendations for the management of adult patients taking antithrombotic agents referred for colonoscopy-polypectomy[311]

* Cold snare polypectomy for lesions under 10 mm in size.

** Coronary artery disease (CAD) without coronary stenting, cerebrovascular disease, peripheral vascular disease; CHA2DS2-VASc score of 4 or less (risk assessment for stroke and systemic thromboembolism in patients with atrial fibrillation); heart valve xenograft; three or more months after venous thromboembolism.

*** Removal of lesions by cold snare resection for lesions larger than 10 mm; EMR/ESD of lesions of any size.

**** CAD with coronary stenting; Aortic or mitral valve replacement; mitral stenosis with atrial fibrillation; Atrial fibrillation with stroke or transient ischemic attack and/or three or more of the following criteria: chronic heart failure/hypertension/age over 75 years/diabetes mellitus; three months or less since atrial fibrillation with stroke or transient ischemic attack; Less than 3 months after venous thromboembolism; Development of venous thromboembolism during anticoagulant therapy.

• Colon wall injuries may occur during diagnostic colonoscopy, biopsy, and are inevitable during the removal of colorectal neoplastic lesions. The extent and depth of the injury range from a superficial mucosal defect to organ perforation and, when resecting neoplasms, are graded in accordance with the Sydney classification of colon wall injury during endoscopic resection [312].

The following types are distinguished:

• Type 0 defect. Conventional post-resection wound. The mucosa with the neoplasm is completely excised, the submucosal layer is partially resected. Obliquely oriented intersecting fibers of the submucosal layer are visible (matte blue if a dyed solution was injected); intact submucosal vessels may be visible. The risk of delayed perforation is absent. Management: this resection can be completed without clipping.

• Type I defect. The mucosa and submucosal layer are completely resected. The muscular layer is visible but mechanically undamaged. The risk of delayed perforation is minimal. Management: this resection can be completed; clipping is at the physician's discretion. Clipping of the wound was performed by the authors of the classification in 31.6% of patients.

• Type II defect. Local loss of the border between the submucosal and muscular layers (typically due to fibrosis), suspicious for muscular layer injury or making the assessment of muscular layer injury impossible. The risk of delayed perforation is 1.7%. Management: prophylactic clipping.

• Type III defect. The muscular layer is injured (partially resected). Defect target sign (DTS) in the post-resection wound or in the resected specimen (specimen target sign = STS). Management: wound clipping to prevent delayed perforation; hospitalization; a short course of broad-spectrum antibiotic therapy; inpatient monitoring in an intensive care/24-hour setting.

• Type IV defect. Apparent / clearly defined opening with a white coagulation ring around it; without visible contamination by intestinal contents. Full-thickness resection with the presence of an opening; the wound is clean (not contaminated with intestinal contents). Management: immediate clipping; hospitalization; antibiotic prophylaxis or therapy in agreement with a clinical pharmacologist; inpatient monitoring in a 24-hour setting.

• Type V defect. Apparent/clearly defined opening with a white coagulation ring around it, with visible contamination by intestinal contents. Full-thickness resection with a perforation opening. Management: emergency hospitalization, deciding on surgical intervention.

• The clinical presentation in the postoperative period depends on the depth and extent of the colon wall injury, as well as the timeliness of complication diagnosis and therapeutic measures taken. Along with non-specific and harmless manifestations of "postoperative discomfort", specific manifestations classified into distinct nosological entities are also distinguished.

• Post-coagulation syndrome (PCS) occurs in 4.8–14.2% of cases and, as the name implies, is associated with thermal injury to the muscular and serous layers of the colon without perforation. Typical manifestations of PCS include: localized pain, tenderness upon palpation, and peritoneal irritation signs in the area of the intervention; fever and chills; elevated leukocyte levels and C-reactive protein. Plain abdominal radiography or abdominal CT scan reveals no signs of perforation. NSAIDs (ATC M01A Non-steroidal anti-inflammatory and antirheumatic products) are prescribed to relieve pain and systemic inflammatory response, while broad-spectrum antibiotics (ATC J01 Antibacterials for systemic use) are administered in agreement with a clinical pharmacologist. The patient is monitored to rule out delayed perforation. Most patients recover without complications, but in some cases, the described clinical picture may be a precursor to delayed perforation [313-316].

• Colon perforation (Type IV or V defect according to the Sydney classification) may develop directly during the endoscopic intervention (intraoperative) and in the postoperative period (delayed perforation). It is important to recognize intraoperative perforation directly during the intervention. In the absence of wound and abdominal cavity contamination (Type IV defect), clipping of the transmural defect is recommended (ideally after complete removal of the neoplasm), along with hospitalization or its extension, antibiotic prophylaxis or therapy in agreement with a clinical pharmacologist, and monitoring in a 24-hour inpatient setting. If endoscopic closure is impossible, surgical intervention is recommended.

• In cases where the wound and abdominal cavity are contaminated with intestinal contents (Type V defect), a multidisciplinary team discussion involving a coloproctologist and a surgeon is recommended. If feasible, perform clipping of the transmural defect, hospitalize the patient or extend the hospital stay, and administer antibiotic prophylaxis or therapy in agreement with a clinical pharmacologist. If endoscopic closure is impossible, surgical intervention is recommended. In case of clinical deterioration, signs of peritonitis, a significant amount of fluid in the abdominal cavity, or incomplete endoscopic resection, surgical treatment is indicated.

• Delayed perforation is a colonic wall perforation diagnosed/developing a certain period of time after endoscopic mucosal resection or endoscopic submucosal dissection. Missed intraoperative perforation is often diagnosed in the immediate postoperative period by the presence of free gas in the abdominal cavity on a plain abdominal radiograph or, preferably, on abdominal CT, which is a more sensitive diagnostic method. "True" delayed perforation caused by deep/transmural bowel wall injury during the intervention (for example, a type III defect according to the Sydney classification) develops at a later stage. The incidence of delayed perforations reaches 1.0–1.9% after endoscopic mucosal resection and 0.1–0.4% after endoscopic submucosal dissection. In most cases, delayed perforation is confirmed within 14 hours after resection; in one third of cases, after 24 hours. Delayed perforation is diagnosed based on the characteristic clinical presentation of hollow viscus perforation into the abdominal cavity/retroperitoneal tissue (signs of intoxication and inflammatory response, abdominal pain and tenderness on palpation, peritoneal signs). The scope and method of emergency surgical intervention are determined depending on the localization of the perforation and the nature of complications.

• Fulminant necrotizing fasciitis (Fournier's gangrene) is rare, but mortality reaches 20–40%. The cause of the syndrome is perforation of the lower ampullary rectum. With infection of the pelvic tissue, the infectious and inflammatory process can spread to the tissues of the perineum and anterior abdominal wall, causing multiple muscle necrosis and inflammation of the surrounding fascia, which can rather rapidly lead to the development of sepsis and disseminated intravascular coagulation (DIC) syndrome. Perforation of the extraperitoneal part of the rectum can be diagnosed as mediastinal emphysema, subcutaneous emphysema, or perirectal abscess. Broad-spectrum antibiotic therapy (ATC J01 Antibacterials for systemic use) and surgical intervention must be initiated immediately.

• Colonic stricture in the area of endoscopic intervention is a late complication, occurs rarely, as a rule, after circular resection/dissection of large lesions, in particular of the rectum. The method of choice in the treatment of this complication is endoscopic balloon dilation of colonic strictures [317, 318].

• Risk factors that increase the probability of adverse events / complications during endoscopic operations, including the risk of post-coagulation syndrome and intestinal wall perforation, include: inadequate preparation of the patient and bowel for the intervention; submucosal fibrosis; lesion size (giant colorectal epithelial neoplasms, over 40 mm, are the most difficult); lesion localization (cecal dome, hepatic and splenic flexures); lesion type and growth pattern; localization in the projection of major vessels; technical unpreparedness and technical difficulty of removing colorectal epithelial neoplasms; low experience of the operating endoscopist; long duration of surgery.

• One of the leading risk factors is submucosal fibrosis, the causes of which include: inflammation; desmoplastic tissue reaction in response to tumor growth; tumor mass effect (usually with a neoplasm size of ≥ 40 mm); non-granular lateral spreading tumors with depression (LST-NG-PD); localization of colorectal epithelial neoplasms in the cecum; tumor growth across a fold; previous biopsy; "test" submucosal injections; incomplete removal with delayed re-intervention, etc. According to severity, submucosal fibrosis is divided into 3 grades: F0, no fibrosis — submucosal layer is transparent; F1, moderate fibrosis — white web-like structure within the transparent submucosal layer; F2, severe fibrosis — white muscle-like structure without a transparent submucosal layer [319].

• Prevention of bowel wall injury, in accordance with known risk factors, begins with adequate patient preparation for the endoscopic intervention and selection of the optimal method for removing colorectal epithelial neoplasms, in accordance with the recommendations formulated in these clinical guidelines. An equally important aspect of preventing potential perforation and choosing the optimal patient management tactics is recognizing the degree of bowel wall injury, for which the Sydney classification is used.

• Infectious complications during colonoscopy.

Infectious complications associated with colonoscopy include transient bacteremia caused by the entry of normal intestinal flora into the bloodstream. The incidence of bacteremia during colonoscopy reaches 4% (from 0 to 25%), however, clinical manifestations of infection (up to registered cases of infective endocarditis) are extremely rare and in most cases do not require antibiotic prophylaxis. Potential infectious complications of colonoscopy also include the development of perirectal abscesses, acute appendicitis, and acute diverticulitis. According to the literature, acute diverticulitis is the most common among these, with an incidence rate within 30 days of colonoscopy reaching up to 0.84 (0.50–1.33) per 1,000 colonoscopies. The risk of complications increases in patients older than 70 years, as well as in the presence of diverticular disease and ASA physical status II–III [320, 321].

Antibacterial therapy for the prevention of infectious complications during colonoscopy is not recommended.

• Cardiorespiratory complications during colonoscopy.

Cardiorespiratory complications associated with colonoscopy include arterial hypotension and hypertension, cardiac arrhythmias, vasovagal reactions, and respiratory failure [320, 321]. The incidence of cardiorespiratory complications varies widely from 0.06 to 19.1%, and in the group of patients older than 80 years reaches 28.9% [320, 322]. The most serious complications in this group are angina pectoris attack, acute myocardial infarction, transient ischemic attack (TIA), and stroke [320, 322]. They are relatively rare but require early differential diagnosis and active management. TIA is the most frequent, with an incidence rate within 30 days of colonoscopy reaching up to 16.8 (16.1–17.6) per 10,000 colonoscopies [320, 323].

It has been proven that in most cases, the development of cardiovascular complications during endoscopic examinations is associated with concomitant pathology: hypertension, coronary artery disease, cardiac arrhythmias, a history of myocardial infarction, stroke, or transient ischemic attacks [324, 325]. Therefore, an initial consultation (examination) by a cardiologist or general practitioner is required before performing a colonoscopy.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Most developers are members of the Association of Coloproctologists of Russia and the Russian Endoscopic Society.

Conflict of interest: none declared by any members of the working group.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience of these clinical guidelines:

1. Endoscopists

2. Gastroenterologists

3. Surgeons

4. Pediatric surgeons

5. Oncologists

6. Coloproctologists

7. Pathologists

8. Anesthesiologists

Methods used for evidence collection/selection: search in electronic databases; analysis of modern scientific developments on epithelial neoplasms of the colon in Russia and abroad; synthesis of practical experience of Russian and foreign specialists.

Scale for assessing the levels of evidence reliability (LER) for diagnostic methods (diagnostic interventions)

Scale for assessing the levels of evidence reliability (LER) for preventive, therapeutic, and rehabilitation methods (preventive, therapeutic, and rehabilitation interventions)

Scale for assessing the levels of recommendation persuasiveness (LRP) for preventive, diagnostic, therapeutic, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Methods used for formulating recommendations – expert consensus.

Economic analysis. Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Method of recommendation validation: external expert review; internal expert review.

Description of the recommendation validation method:

The preliminary version of these clinical guidelines was reviewed by independent experts who were asked to comment on whether the interpretation of the evidence underlying the recommendations was easy to understand.

Comments were received from primary care endoscopists regarding the clarity of the presentation of the recommendations and their importance as a working tool in daily practice.

Comments received from experts were carefully systematized and discussed by the heads and members of the working group. Every item of changes made to the recommendations was registered. If no changes were made, the reasons for refusing to make changes were recorded.

Consultations and peer review: the draft guidelines were also reviewed by independent experts who were asked to comment on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.

For final editing and quality control, the clinical guidelines were re-analyzed by the working group members, who concluded that all comments and feedback from the experts had been taken into account, and the risk of bias in the development of the guidelines was minimized.

Updating of clinical guidelines: updating is carried out at least once every 3 years, taking into account new information on the diagnosis and management of patients with epithelial neoplasms of the colon. The decision to update is made by the Russian Ministry of Health based on proposals submitted by the Association of Coloproctologists of Russia. The formulated proposals must take into account the results of a comprehensive evaluation of drugs and medical devices, as well as the results of clinical approbation.

When selecting publications as sources of evidence, the methodology used in each study is examined to ensure its reliability. The result of the examination affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendations derived from it.

Appendix A3. Reference Materials

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

1. Order of the Ministry of Health of the Russian Federation No. 9222n dated November 15, 2012 "On approval of the Procedure for providing medical care to the adult population in the profile 'surgery';

2. Order of the Ministry of Health and Social Development of the Russian Federation No. 206n dated April 2, 2010 "On approval of the Procedure for providing medical care to the population with diseases of the colon, anal canal and perineum in the coloproctological profile" (with amendments and additions);

3. Order of the Russian Ministry of Health No. 974 dated December 6, 2017 "On approval of the Rules for conducting endoscopic examinations";

4. Order of the Ministry of Health of the Russian Federation No. 179n dated March 24, 2016 "On the Rules for conducting pathoanatomical examinations";

5. Order of the Russian Ministry of Health No. 1177n dated December 20, 2012 (as amended on July 17, 2019) "On approval of the procedure for giving informed voluntary consent to medical intervention and refusal of medical intervention for certain types of medical interventions, forms of informed voluntary consent to medical intervention and forms of refusal of medical intervention";

6. Order of the Russian Ministry of Health No. 404n dated April 27, 2021 (as amended on February 1, 2022) "On approval of the Procedure for conducting preventive medical examinations and clinical examinations (dispensary evaluation) of certain groups of the adult population");

7. Order of the Ministry of Health of the Russian Federation No. 928n dated November 15, 2012 "On approval of the Procedure for the provision of medical care to patients with acute cerebrovascular accidents").

Appendix B. Physician Action Algorithms

Appendix B1. Endoscopist Algorithm of Actions

Appendix B2. Algorithm of actions for an endoscopist upon detection of epithelial laterally spreading neoplasms of the colon

Appendix B3. Algorithm of actions for an endoscopist upon detection of serrated epithelial neoplasms of the colon

Appendix B4. Management Tactics for Patients with Delayed Bleeding

Appendix C. Patient Information

What are colonic polyps?

The cells of the intestinal mucosa are regularly renewed, and complete replacement of the cells of the inner layer occurs every 3–4 days. If this process is disrupted, local outgrowths—polyps—form on the surface of the mucosa.

A colonic polyp is a benign tumor, but it commands close attention from oncologists.

Classification

The most common group is adenomatous polyps, the so-called adenomas. They are caused by a mutation in the APC gene. As a result of this mutation, cells begin to divide faster, excess cell clusters form, and polyps appear. It is important to note that a single APC gene mutation is not enough for the malignant transformation of an adenoma into cancer; a combination of this mutation with others is necessary, primarily the p53 or KRas gene. However, the risk of cancer increases with the formation of polyps and the APC mutation.

In rare cases, people are born with an APC mutation in all cells, resulting in a disease known as familial adenomatous polyposis of the colon. In this condition, hundreds or even thousands of polyps form in the intestine. This condition requires surgical removal of the colon, as there is a high risk of developing cancer when concomitant mutations appear.

Adenomas are classified histologically into tubular, villous, and mixed tubulovillous.

This finding is important because the villous type has a greater tendency toward malignant transformation and requires closer monitoring if the polyp has not been removed.

Another classification is based on external features, primarily taking into account whether the polyp has a stalk connecting it to the intestinal wall (resembling a mushroom in appearance), or whether it has a "sessile," flattened shape, meaning it is firmly attached to the wall. There are also differences here: such "sessile" polyps are more likely to become malignant.

Another group of intestinal polyps consists of serrated polyps, or serrated adenomas. This group has gained importance in recent years. They got their name due to the characteristic appearance of their cells under a microscope. "CpG islands" form inside their DNA, which, while not mutations per se, promote malignant cell transformation under the potential influence of various other mutagenic factors. Serrated polyps are of two types: small ones, morphologically defined as hyperplastic, and larger, flattened forms, which carry a higher risk of malignant transformation.

The third group is inflammatory polyps, which often accompany inflammatory bowel diseases (ulcerative colitis and Crohn's disease). These polyps are modified scars and carry no oncological risk.

The final, fourth group is hamartomatous polyps, whose cells have a distorted structure resembling mixed tissues. This type of polyp is associated with hereditary syndromes and diseases (juvenile polyposis, Peutz-Jeghers syndrome, etc.).

Risk factors

Risk factors for developing polyps include anything that promotes mutations in intensively dividing cells of the inner lining of the colon. This is primarily a hereditary predisposition (the presence of polyps or colon cancer in close relatives). Advanced age: after 50 years, the risks of polyps and colon cancer increase.

The third group includes unfavorable environmental factors: smoking, overeating, sedentary lifestyle, occupational hazards, nervous stress, etc., which are also frequently associated with polyps.

A separate group consists of patients with long-standing inflammatory bowel disease; detecting an adenoma in such a patient is a warning sign and requires careful, regular monitoring.

Clinical manifestations

In most cases, polyps are asymptomatic and are an incidental finding during screening colonoscopy.

However, in some cases, a large polyp bleeds, manifesting as rectal bleeding or even leading to anemia.

Cases of intestinal obstruction caused by benign polyps are extremely rare.

Treatment

Polyps are generally removed via colonoscopy using a special snare; this procedure is called a polypectomy.

Large polyps may require surgical resection of an entire segment of the colon, performed in the operating room with an abdominal wall incision.

Currently, the method of endoscopic submucosal dissection (ESD) is gaining popularity. In this method, the polyp is removed along with the adjacent intestinal wall through a colonoscope. This method allows for the minimally invasive removal of large polyps.

The removed polyp is examined under a microscope to definitively and accurately determine its type and reliably rule out foci of malignant transformation.

Prevention

Following polypectomy, patients undergo periodic surveillance colonoscopies. The frequency of these examinations depends on the size and type of the removed polyp. In the absence of new polyps, colonoscopy can be performed less frequently.

For early detection of polyps, a colonoscopy is recommended after the age of 50.

Dietary composition and standards influence the prevention of polyp growth. Studies have shown that eating vegetables (potatoes, lettuce, cabbage, legumes), thanks to their dietary fiber content, prevents the development of polyps and colon cancer. Experts also advise eating less fat and consuming more fish and "white" meat (e.g., poultry).

Quitting smoking, reducing alcohol consumption, achieving a normal weight, and increasing physical activity also reduce the risk of polyp growth.

Conclusion:

− A colonic polyp is a benign tumor, but it can degenerate into cancer.

− The greatest danger in terms of malignant transformation is posed by adenomas and serrated polyps.

− The risk of having polyps increases if polyps are found in relatives and at an age over 50.

− Polyps are usually detected and removed during colonoscopy.

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

Appendix G1. Boston Bowel Preparation Scale

Russian title: Boston Bowel Preparation Scale.

Original title: The Boston Bowel Preparation Scale (BBPS).

Source (official developer website, validation publication): https://www.giejournal.org/article/S0016-5107(08)01988-3/abstract

Original publication: Lai EJ, Calderwood AH, Doros G, Fix OK, Jacobson BC. The Boston bowel preparation scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc. 2009 Mar;69(3 Pt 2):620-5. doi: 10.1016/j.gie.2008.05.057. Epub 2009 Jan 10. PMID: 19136102; PMCID: PMC2763922 [326].

Type: rating scale.

Purpose: to describe the quality of patient bowel preparation for colonoscopy in order to increase the accuracy and reliability of colonoscopy results.

Content (template):

Key (interpretation): provided within the scale itself.

*In accordance with the author's terms of use for the Boston scale, the assessment of colonic preparation for endoscopic examination is carried out after the endoscopist has performed washing and aspiration of the contents!

A scoring system (from 0 to 3) is used to assess the quality of preparation for endoscopic examination of each of the 3 segments of the colon. The evaluated segments are: the right colon; the transverse colon; and the left colon. Each evaluated colonic segment is assigned a score ranging from 0 to 3, with scores of 2 and 3 indicating that the respective segment is adequately prepared for endoscopic examination; conversely, scores of 0 and 1 indicate inadequate preparation, unsuitable for a complete examination. After assessing each segment, the overall bowel preparation score is calculated as the sum of the scores of all three segments, resulting in a total score ranging from 0 to 9. The maximum total score for the quality of colonic preparation for endoscopic examination is 9 points (ideal preparation), and the minimum score (none of the segments are prepared for examination) is 0 points.

The range of adequate colonic preparation for endoscopic examination is 6 to 9 points, subject to a very important condition (!): the quality score of each evaluated colonic segment must be at least 2 points.

Appendix G2. AGREE Classification of Adverse Events/Complications in Gastrointestinal Endoscopy

AGREE Classification – an endoscopy-adapted version of the Clavien-Dindo surgical complication classification. According to 57 international endoscopy experts who participated in its validation, the AGREE classification is simple – 86%, reproducible – 98%, logical – 98%, and useful – 96%. The correct complication category was assigned in 84% of all test clinical cases. Complications are defined as any negative consequences for the patient that prevent the completion of the planned intervention or cause any deviation from the standard postoperative course (within 30 days!). Unplanned events and occurrences during the intervention that did not affect the standard postoperative course are not considered complications.

Appendix G3. ASA Physical Status Classification System

ASA (American Society of Anaesthesiologists).

Russian title: American Society of Anesthesiologists Physical Status Classification System.

Original name: ASA Physical Status Classification System.

Source (official developer website, validation publication): https://ekja.org/journal/view.php?doi=10.4097/kja.d.18.00224

Original publication: De Cassai A, Boscolo A, Tonetti T, Ban I, Ori C. Assignment of ASA-physical status relates to anesthesiologists' experience: a survey-based national-study. Korean J Anesthesiol. 2019 Feb;72(1):53-59 [327].

Type: scale.

Purpose: assessment of the patient's physical status prior to surgery.

Content (template): to determine the patient's status, the anesthesiologist-resuscitator uses the following patient data: complaints, medical history, physical examination data, laboratory and diagnostic test results, and instrumental examination results.

Key (interpretation): depending on the data obtained during history-taking and patient examination, the patient is assigned to one of the following groups:

I – normal healthy patient (nonsmoker, no regular alcohol use).

II – patient with mild systemic disease of moderate severity (smoker, alcohol user, pregnant, obesity with a body mass index of 30 to 40, arterial hypertension, compensated diabetes mellitus, mild pulmonary disease).

III – patient with severe systemic disease that limits activity. One or more moderate-severity conditions (decompensated or poorly controlled diabetes mellitus, end-stage chronic kidney disease with regular hemodialysis, implanted pacemaker, myocardial infarction > 3 months ago, chronic obstructive pulmonary disease, uncompensated arterial hypertension, obesity with a body mass index > 40).

IV – patient with severe disease that is a constant threat to life (stroke or myocardial infarction < 3 months ago, severe cardiac valvular disease, sepsis, disseminated intravascular coagulation syndrome, severe left ventricular ejection fraction reduction, end-stage chronic kidney disease with irregular hemodialysis).

V – moribund patient who is not expected to survive without surgery (ruptured aortic aneurysm, intracranial hemorrhage with mass effect, massive trauma, multiorgan failure, bowel ischemia combined with severe cardiac pathology).

VI – brain-dead patient whose organs are being harvested for donor transplant.

E – Emergency intervention.