Authors

  • B. Mirzayev
    Fergana Medical Institute of Public Health
  • D. Kholbekov
    Fergana Medical Institute of Public Health

DOI:

https://doi.org/10.71337/inlibrary.uz.jmsi.113449

Abstract

Non-specific ulcerative colitis (NUC) is a chronic autoimmune inflammatory disease of the colon with a relapsing course, characterized by mucopurulent and bloody discharge from the intestine, abdominal pain and systemic manifestations. The incidence of UC has traditionally been high in Western countries, but in recent decades its growth has been observed in the regions of Asia and the CIS. The mechanisms of development of UC include genetic predisposition (many polymorphisms of interleukins and HLA), immunoregulation disorders (imbalance of Th1/Th2 response, excessive expression of TNF-α, IL-13, etc.) and dysbiosis of intestinal microbiota . The leading method of radical treatment of UC is colectomy with formation of ileoanal anastomosis (IAA), which is used in severe exacerbations and complications (toxic megacolon, uncontrolled bleeding, perforation, dysplasia/carcinoma) or in relapses refractory to therapy. Modern minimally invasive technologies ( laparoscopy , robots) can reduce postoperative complications and shorten the duration of hospitalization. The review considers international and regional epidemiological data on UC, modern concepts of etiopathogenesis , clinical picture and indications for surgery, as well as modern surgical approaches and unresolved issues.


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NON-SPECIFIC ULCERATIVE COLITIS: EPIDEMIOLOGY, ETIO-PATHOGENESIS

AND ISSUES OF SURGICAL TREATMENT

B.B. Mirzayev ,

D. Kholbekov

Fergana Medical Institute of Public Health

Abstract:

Non-specific ulcerative colitis (NUC) is a chronic autoimmune inflammatory disease

of the colon with a relapsing course, characterized by mucopurulent and bloody discharge from

the intestine, abdominal pain and systemic manifestations. The incidence of UC has traditionally

been high in Western countries, but in recent decades its growth has been observed in the regions

of Asia and the CIS. The mechanisms of development of UC include genetic predisposition

(many polymorphisms of interleukins and HLA), immunoregulation disorders (imbalance of

Th1/Th2 response, excessive expression of TNF-α, IL-13, etc.) and dysbiosis of intestinal

microbiota . The leading method of radical treatment of UC is colectomy with formation of

ileoanal anastomosis (IAA), which is used in severe exacerbations and complications (toxic

megacolon, uncontrolled bleeding, perforation, dysplasia/carcinoma) or in relapses refractory to

therapy. Modern minimally invasive technologies ( laparoscopy , robots) can reduce

postoperative complications and shorten the duration of hospitalization. The review considers

international and regional epidemiological data on UC, modern concepts of etiopathogenesis ,

clinical picture and indications for surgery, as well as modern surgical approaches and

unresolved issues.

Key words:

nonspecific ulcerative colitis, epidemiology, pathogenesis, surgical treatment,

minimally invasive technologies, intestinal microbiota .

Introduction

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and is characterized by a

persistent, relapsing course. It is characterized by chronic inflammation of the colonic mucosa,

primarily affecting the rectum and spreading further, and in severe cases, total colon

involvement [1,5,6]. The disease usually debuts at a young age (15–30 years), but a secondary

peak in incidence is also possible in old age. Ulcerative colitis is estimated to account for

approximately 20–30% of all IBD cases and causes hundreds of thousands of visits to physicians

each year; in the United States, annual direct medical costs for UC reach several billion dollars.

Constant exacerbations reduce the quality of life of patients, and surgical treatment is required

for a significant number of patients: according to large studies, only about 10% of patients with

UC require colectomy within 20 years of diagnosis . The increase in the incidence of IBD,

including UC, in countries with low and medium levels of development (Asia, the Middle East,

the CIS) increases the relevance of studying this pathology at the international and regional

levels [11,12,14]. In this regard, the review presents current data on the epidemiology of UC, the

main pathogenetic mechanisms, clinical manifestations and indications for surgical treatment,

existing approaches to surgery and prospects for further research.

Epidemiology of UC


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UC is widespread, but there are significant geographical differences. The highest incidence is

traditionally observed in Northern Europe and North America – up to 20–25 new cases per year

per 100,000 population. For comparison, in Eastern Europe and Asia these rates are significantly

lower (approximately 5–12/100,000 per year). According to meta-analyses and reviews, the

current prevalence of UC in Western countries reaches 150–300 per 100,000 population. At the

same time, in many regions with low incidence, a steady increase has been observed in recent

decades. For example, in South Korea, the annual incidence of UC increased from 0.33 to 6.58

cases per 100,000 population during 1986–2015, and in Japan, from 0.03 to 12.2/100,000 during

1955–2014. According to the review, in East Asia, about 0.1–0.2% of the population has IBD. In

South Asian countries (India, Pakistan, Sri Lanka), the average incidence is lower (several cases

per 100,000).

Data for the CIS and Central Asian regions are limited. In Kazakhstan, the prevalence of UC is

84.4 cases per 100,000 population (total IBD is 113.9/100,000). In Uzbekistan and other Central

Asian countries, there have been virtually no specialized epidemiological studies, so there are no

accurate statistics. In general, there are few studies in Central Asia, which makes it difficult to

assess the actual incidence of IBD. Thus, global trends show stabilization or a slight decrease in

incidence rates in developed countries, while there is rapid growth in developing regions of the

world.

Etiopathogenesis

The causes of UC are complex and include the interaction of genetic factors, immune disorders,

changes in microbiota and external factors. It is generally accepted that UC develops against the

background of genetic predisposition and immune regulation disorders . Thus, having a close

relative with UC increases the risk of the disease by approximately 4 times. Many

polymorphisms of genes associated with inflammation regulation (IL23R, IL12B, IL10, HLA,

etc.) have been identified; genetic studies of recent years emphasize the influence of variations in

interleukins and their receptors on the predisposition to UC.

Immunopathogenesis of UC is characterized by an excessive inflammatory response to

environmental factors and microbial antigens. In UC, a predominantly Th2-type response is

observed (in contrast to Th1/Th17 in Crohn's disease) - cytotoxic CD4^+^ Th2 cells are

activated, levels of IL-13, as well as TNF-α and other proinflammatory cytokines are increased.

Innate components of immunity play an important role: patients have been shown to have

dysfunction of the epithelial barrier (impaired mucin composition and cellular contacts), as well

as increased expression of TL receptors on dendritic cells of the mucosa [2,3,15,26]. Against the

background of barrier impairment, commensal intestinal bacteria can provoke an excessive

immune response. The result is a chronic disruption of the "microbe - immune system"

homeostasis: the composition and diversity of the microbiota changes , which further stimulates

inflammation and damage to the intestinal mucosa. In particular, with UC, there is a decrease in

the number of beneficial bacteria ( Faecalibacterium prausnitzii , etc.) and an increase in

opportunistic strains, which can be both a cause and a consequence of inflammation [30,32,34].

External environmental factors also modify the risk of UC. Among them, smoking has been

studied the most: interestingly, smokers are less likely to develop UC, and in former smokers,

the disease often proceeds more severely [4,5,6]. Exacerbation of UC may develop upon quitting

smoking. Appendectomy at a young age is associated with a decrease in the risk of UC (by about

69%). The attractiveness of the "Western" lifestyle (diet with a predominance of fats and sugars,

lack of fiber) and the use of a number of drugs (NSAIDs, oral contraceptives) are discussed as

potential risk factors. Thus, it is known that non-steroidal anti-inflammatory drugs often provoke

relapses of UC [7,8,13,14]. The influence of warm moist infections and antibiotics, which

disrupt the intestinal microbiota , is also assumed . Together, all these factors contribute to the


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high variability of the course of UC, but the exact mechanisms are still not fully understood.

Clinical picture and indications for surgery
UC is characterized by a chronic remitting course with acute and latent phases. The main

symptoms are diarrhea with blood and mucus, abdominal pain (usually in the left iliac region),

tenesmus and false urges (imperative urges without evacuation). Non-specific manifestations are

often added - weight loss, subfebrile temperature, anemia, general weakness [18,21,22,30]. The

course of UC is variable: from proctitis, in which only the rectum is affected (which occurs in

30-60% of patients at debut), to left-sided colitis (16-45%) and total ( pancolitis ) (14-35%). On

examination, the intestine looks "fragile", with an erased vascular pattern, erythematous and

ulcerated areas, evenly spreading from the rectum to the proximal parts. Important markers of

activity are elevated ESR, CRP, leukocytosis, and in 60–70% of cases, the presence of

perinuclear ANCA (p-ANCA) [9,10,11,18]. UC is often accompanied by extraintestinal

manifestations: 10–30% of patients develop arthritis, eye inflammation ( episcleritis , uveitis ),

skin diseases (erythema nodosa , pyoderma gangrenosum ), and other inflammations associated

with colitis activity. Chronic UC is associated with primary sclerosing cholangitis (PSC), which

increases the risk of colorectal cancer.

Despite the improvement of medical treatment (5-aminosalicylates, glucocorticoids,

immunosuppressants, biological drugs), a significant proportion of patients sooner or later

require surgical treatment [22,23,26,35,38]. Various studies note that from 10% to 30-40% of

patients with UC undergo colectomy during their life . Indications for surgery are divided into

emergency and planned. Emergency indications include severe complications or a life-

threatening condition: acute severe colitis that cannot be relieved with medication, toxic

megacolon (extensive expansion of the colon with a toxic state), massive bleeding, intestinal

perforation. In such situations, an urgent subtotal colectomy is performed with the formation of

an ileostomy , often with preservation of the rectum ( Hartmann stages), or a proctocolectomy

with an ileostomy or ileoanal anastomosis is performed immediately , depending on the patient's

condition. Elective indications for colectomy include failure of long-term drug therapy (relapses

after multiple courses of therapy), low quality of life with persistent symptoms, dysplasia or

early colon cancer in UC. If high-grade dysplasia or cancer is detected, colorectal risk is

considered an indication for total proctocolectomy with ileoanal anastomosis. The choice of

surgical tactics is largely determined by the severity and extent of inflammation, as well as the

general condition of the patient.

Modern approaches to surgical treatment

Surgical treatment of UC is considered radical and can lead to complete disappearance of

intestinal symptoms, but surgery is a serious intervention with its own risks. In UC treatment

programs, the main role is given to total proctocolectomy with the formation of an ileoanal

anastomosis (IAA), which allows preserving the anal sphincter [14,17,19,25,26]. Classically, this

operation is performed in 2-3 stages (to reduce the risk of taking corticosteroids): first, removal

of the colon and formation of a temporary ileostomy (preservation of the rectum or its suturing),

then removal of the rectum and restoration of the intestine from the ileal loop. In emergency

cases, a less radical operation is often performed - subtotal colectomy with ileostomy ( Hartman

technique ) to stabilize the patient, and then, during the second operation, complete the removal

of the rectum and form the anastomosis.

In recent decades, laparoscopic technique has become the standard of preparation for colorectal

surgery . Laparoscopy in UC has a proven effect of reducing postoperative morbidity, the

number of early complications (including incisional infections) and shortens the duration of

hospitalization [16,18,20, 31-33]. Randomized and observational studies have shown that with


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laparoscopic IARA, the overall complication rate is comparable to open surgery (odds ratio

≈1.12 without statistical difference), but the duration of the operation is usually longer. At the

same time, after laparoscopy, the average duration of hospitalization is significantly shorter (in

the meta-analysis 11.2 ± 4.8 days versus 26.4 ± 4.3 days with open surgery). In addition, the

tolerability of laparoscopy is especially important in young patients with a potentially large

number of surgeries. A systematic review showed that laparoscopic intestinal restoration (IARA)

provides comparable results with open access in terms of morbidity and mortality. Several

studies have noted the benefit of laparoscopy in reducing the incidence of short-term

complications in patients who received corticosteroids before surgery.

In addition to classical laparoscopy, robotic technologies and single-laparoscopic access are used

in modern proctology. Robotic proctocolectomy allows for more precise work in the pelvis and

can reduce the conversion rate in complex cases, although the final results are still limited to

small series. Single-incision techniques (SILS) and trans-anal approaches are also being actively

introduced for outpatient expansion of indications. An important aspect is the minimization of

the number of operations and stages: in a favorable situation, one-stage IARA can be performed,

but in high-risk patients (immunosuppression, active inflammation), two- or three-stage options

are more often used. In general, modern surgical approaches seek to ensure complete removal of

the inflammation focus and adequate intestinal reconstruction with minimal trauma.

Conclusion.

Thus, despite the progress in understanding UC, many aspects remain incompletely

understood. The etiology of the disease remains unclear: it is unknown which specific

environmental triggers initiate the inflammatory cascade in genetically susceptible individuals

and how immune and metabolic disturbances influence it. The exact role of the gut microbiota

remains to be determined : although dysbiosis in UC has been documented, therapeutic methods

of flora correction (e.g. faecal microbiota transplantation ) have not yet become standard

treatment. Genetic studies are constantly expanding the list of associated loci, but still do not

explain all clinical phenotypes of UC.

List literature :

1. Gros B., Kaplan GG Ulcerative colitis in adults: a review // JAMA. – 2023. – Vol. 330, No. 10.

– P. 951–965.

2. Le Berre C., Honap S., Peyrin-Biroulet L. Ulcerative colitis // Lancet. – 2023. – Vol. 402, No.

10401. – P. 571–584.

3. Segal JP, LeBlanc J.-F., Hart AL Ulcerative colitis: an update // Clin . Med. ( Lond .). – 2021.

– Vol. 21, No. 2. – P. 135–139.

4. Porter RJ, Kalla R., Ho G.-T. Ulcerative colitis: Recent advances in the understanding of

disease pathogenesis // F1000Res. – 2020. – Vol. 9. – Article 294.

5. Pravda J. Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for

colonic epithelial hydrogen peroxide // World J. Gastroenterol . – 2022. – Vol. 28, No. 31. – P.

4263–4298.

6. Kilic Y., Kamal S., Jaffar F., et al. Prevalence of extraintestinal manifestations in

inflammatory bowel disease: a systematic review and meta-analysis // Inflamm . Bowel Dis. –

2024. – Vol. 30, No. 2. – P. 230–239.

7. Limsrivilai J, Lai AY-H, Li STH, et al. Role of 5-aminosalicylic acid in ulcerative colitis

management in 8 Asian territories: a physician survey // Intest . Res. – 2025. – Vol. 23, No. 2. –

P. 117–128.


background image

https://ijmri.de/index.php/jmsi

volume 4, issue 4, 2025

1080

8. Horesh N., Wexner SD Fecal microbiota transplantation for patients with ulcerative colitis: a

systematic review and meta-analysis of randomized controlled trials // BMC Gastroenterol . –

2025. – Vol. 25. – P. 1–13.

9. Park SH, Jang BI, Kim TO, et al. Update on inflammatory bowel disease epidemiology in

Asia // Intest . Res. – 2022. – Vol. 20, No. 2. – P. 159–164.

10. Lyukmayev V. Yu ., Shushera VE, Orlova MA et al. Ulcerative colitis (review) //

Gastroenterol . Hepatol . Polymed . – 2021. – Vol. 18, No. 3. – P. 52–59. ( on ( Russian

language )

11. Farraye FA, Moss AC, Shaheen NJ, et al. ACG Clinical Guideline: Ulcerative Colitis in

Adults // Am. J. Gastroenterol . – 2019. – Vol. 114, No. 3. – P. 384–413.

12. Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: Ulcerative

Colitis in Adults // Am. J. Gastroenterol . – 2019. – Vol. 114, No. 4. – P. 384–413.

13. Narula N., Peerani F., Kushnir V. et al. Fecal microbiota transplant for ulcerative colitis – a

systematic review and meta-analysis // Inflamm . Bowel Dis. – 2017. – Vol. 23, No. 10. – P.

1702–1709.

14. Fujiwara D., Maeda Y., Kajii E. et al. Mucosal healing in clinical practice: how useful is

fecal calprotectin ? // Inflamm . Bowel Dis. – 2013. – Vol. 19, No. 6. – P. 1437–1444.

15. Kornbluth A., Sachar DB Ulcerative colitis practice guidelines in adults: ACG, ECCO, and

World Gastroenterology Organization perspectives // Mayo Clin . Proc. – 2010. – Vol. 85, Suppl.

– S1–S42.

16. Panaccione R., Ghosh S., Middleton S., et al. Combination therapy with infliximab and

azathioprine is superior to monotherapy with either agent in ulcerative colitis // Gastroenterology.

– 2014. – Vol. 146, No. 2. – P. 392–400.

17. Kaser A., Zeissig S., Blumberg RS Inflammatory bowel disease // Annu . Rev. Immunol . –

2010. – Vol. 28. – P. 573–621.

18. Abraham C., Cho JH Inflammatory bowel disease // N. Engl. J. Med. – 2009. – Vol. 361, No.

21. – P. 2066–2078.

19. Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis // Lancet. – 2017. – Vol. 389, No.

10080. – P. 1756–1770.

20. Yanai H., Hanauer S. Imaging in inflammatory bowel disease // Gastroenterology. – 2011. –

Vol. 140, No. 6. – P. 1962–1975.e3.

21. Neurath MF, Travis SP Mucosal healing in inflammatory bowel diseases: a systematic

review // Gut. – 2012. – Vol. 61, No. 11. – P. 1619–1635.

22. Bernstein CN, Blanchard JF, Rawsthorne P., Wajda A. Epidemiology of Crohn's disease and

ulcerative colitis in a central Canadian province: a population-based study // Am. J. Epidemiol .

– 1999. – Vol. 149, No. 10. – P. 916–924.

23. Jess T., Gamborg M., Munkholm P., Sørensen TI Overall and cause-specific mortality in

ulcerative colitis: meta-analysis of population-based inception cohort studies // Am. J.

Gastroenterol . – 2007. – Vol. 102, No. 3. – P. 609–617.

24. Cosnes J., Gower-Rousseau C., Seksik P., Cortot A. Epidemiology and natural history of


background image

https://ijmri.de/index.php/jmsi

volume 4, issue 4, 2025

1081

inflammatory bowel diseases // Gastroenterology. – 2011. – Vol. 140, No. 6. – P. 1785–1794.

25. Bernstein CN, Loftus EV Jr., Ng SC, et al. World Gastroenterology Organization Practice

Guidelines for the diagnosis and management of IBD in 2010 // Inflamm . Bowel Dis. – 2010. –

Vol. 16, No. 1. – P. 112–124.

26. Vazeille E., Corriente S., Branger J. Predictors of corticosteroid failure in severe ulcerative

colitis: a systematic review // Gut. – 2013. – Vol. 62, Suppl. 2. – A77. ( Abstract )

27. Turner D, Levin MD, Bergeron J, et al. Severity of bleeding and outcome in pediatric

ulcerative colitis // Inflamm . Bowel Dis. – 2009. – Vol. 15, No. 4. – P. 575–580.

28. Rutgeerts P., Sandborn W\.J., Feagan BG, et al. Infliximab for induction and maintenance

therapy for ulcerative colitis // N. Engl. J. Med. – 2005. – Vol. 353, No. 23. – P. 2462–2476.

29. Sandborn W\.J., Feagan BG, Rutgeerts P., et al. Adalimumab induces and maintains clinical

remission in patients with moderate-to-severe ulcerative colitis // Gastroenterology. – 2012. –

Vol. 142, No. 2. – P. 257–265.

30. Travis SP, Stange EF, Lémann M, et al. European evidence-based consensus on the

management of ulcerative colitis: current management // J. Crohns Colitis. – 2008. – Vol. 2, No.

1. – P. 24–62.

References

Gros B., Kaplan GG Ulcerative colitis in adults: a review // JAMA. – 2023. – Vol. 330, No. 10. – P. 951–965.

Le Berre C., Honap S., Peyrin-Biroulet L. Ulcerative colitis // Lancet. – 2023. – Vol. 402, No. 10401. – P. 571–584.

Segal JP, LeBlanc J.-F., Hart AL Ulcerative colitis: an update // Clin . Med. ( Lond .). – 2021. – Vol. 21, No. 2. – P. 135–139.

Porter RJ, Kalla R., Ho G.-T. Ulcerative colitis: Recent advances in the understanding of disease pathogenesis // F1000Res. – 2020. – Vol. 9. – Article 294.

Pravda J. Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide // World J. Gastroenterol . – 2022. – Vol. 28, No. 31. – P. 4263–4298.

Kilic Y., Kamal S., Jaffar F., et al. Prevalence of extraintestinal manifestations in inflammatory bowel disease: a systematic review and meta-analysis // Inflamm . Bowel Dis. – 2024. – Vol. 30, No. 2. – P. 230–239.

Limsrivilai J, Lai AY-H, Li STH, et al. Role of 5-aminosalicylic acid in ulcerative colitis management in 8 Asian territories: a physician survey // Intest . Res. – 2025. – Vol. 23, No. 2. – P. 117–128.

Horesh N., Wexner SD Fecal microbiota transplantation for patients with ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials // BMC Gastroenterol . – 2025. – Vol. 25. – P. 1–13.

Park SH, Jang BI, Kim TO, et al. Update on inflammatory bowel disease epidemiology in Asia // Intest . Res. – 2022. – Vol. 20, No. 2. – P. 159–164.

Lyukmayev V. Yu ., Shushera VE, Orlova MA et al. Ulcerative colitis (review) // Gastroenterol . Hepatol . Polymed . – 2021. – Vol. 18, No. 3. – P. 52–59. ( on ( Russian language )