Both forms of IBD are associated with an increased incidence of gastrointestinal cancer, in addition, both begin relatively early in life and persist for long periods, leading to decreased quality of life indices and a greater than two fold increase in mortality rate.^1-4 It was generally believed that chronic idiopathic ulcerative colitis (IUC) and Crohn's disease were rarely seen in underdeveloped nations, including middle eastern, Asian and African countries.^5,6,7

The last 2 decades have seen an increase in the reports of both ulcerative colitis (UC) and Crohn’s disease (CD) from Asian countries. ^8-11

Patients with long-standing ulcerative colitis (UC) and Crohn’s disease of the colon are at an increased risk of developing colorectal neoplasia (dysplasia and colorectal carcinoma.^12,13 In inflammatory bowel disease (IBD) the development of colorectal carcinoma (CRC) occurs through an inflammation-dysplasia-carcinoma pathway.¹³ In contrast to patients with sporadic CRC, individuals with IBD-related CRC have an increased incidence of synchronous malignancies, an absence of adenomatous polyps preceding the development of carcinoma, and a more rapid rate of progression of colonic mucosa to dysplasia.^12-22

Although CRC, complicating ulcerative colitis and Crohn’s disease, only accounts for 1–2% of all cases of CRC in the general population, it is considered a serious sequela of the disease and accounts for one in six of all deaths in IBD patients.^12-22

Colorectal cancer, the most lethal long term complication of chronic inflammatory bowel disease (IBD), is the culmination of a complex sequence of molecular and histologic derangements of the intestinal epithelium that are initiated and at least partially sustained by chronic inflammation. Dysplasia, the earliest histologic manifestation of this process, plays an important role in cancer prevention by providing the first clinical alert that this sequence is underway and serving as an endpoint in colonoscopic surveillance of patients at high risk for colorectal cancer.^15-22

The diagnosis and grading of dysplasia in endoscopic surveillance biopsies play a decisive role in the management of patients with IBD.^15,16,17,18

The current approach to surveillance is grounded in the concept of an inflammation-dysplasia-carcinoma sequence, with dysplasia representing a premalignant phase during which intervention can prevent or minimize the complications associated with invasive cancer. Dysplasia, the earliest histologic manifestation of this process, plays an important role in cancer prevention by providing the first clinical alert that this sequence is underway and serving as an endpoint in colonoscopic surveillance of patients at high risk for CRC. The diagnosis and grading of dysplasia in endoscopic surveillance biopsies plays a decisive role in the management of patients with IBD.^15-22

MATERIAL AND METHODS

This Hospital based four years prospective observational study was done in the department of pathology, Government Medical College Baramulla  extending from march 2021 to march 2025. Histopathologically and endoscopically confirmed cases of IBD 0n regular follow up were included in the study, patients who did not come for follow up were excluded from the study. During this period follow up endoscopic surveillance biopsies of 210 IBD patients were studied for dysplasia. Dysplasia was divided into negative for dysplasia, low grade, high grade and indefinite for dysplasia. Indefinite group was sent for repeat endoscopic biopsies. Biopsies received in 10% formalin were processed as per the standard procedure and studied by two senior most pathologists in the department of pathology for dysplasia.

RESULTS:

Age of the IBD patients ranged from 1 to 80 years. Mean age was 39.75 years. Maximum number of  IBD cases were seen  in the age group 20-30  years (49 cases, 23.33%), followed by 40-50 years (43 cases, 20.47%) and 30-40 years age group (42 cases, 20%). Only in (2 cases 0.95%) age was less than ten years. Males were 127 (60.5%) cases of inflammatory bowel disease and females were 83 cases (39.5%). Male: Female ratio was 1.53:1.

Pain abdomen, Bloody diarrhoea, Diarrhoea, and Hematochesia were dominant symptoms.  Extra intestinal manifestations in the form of arthritis was present in four patients (1.90%).

Mean duration of disease was 2.43 years. Duration of disease was less than 1 year in 78.57% patients, 1 to 10years in 14.76% patients and greater than 10 years in 5.71% patients.

Haemorrhagic spots, ulcerated, erythematous and friable areas, loss of vascularity and oedema were dominant endoscopic findings. (graph 1)

Ulcerative colitis was present in 182 patients (86.6%), Crohn disease in 26 patients (12.38%) and Indeterminate colitis in 2 patients (0.95%). All Crohn’s disease and indeterminate colitis patients were negative for dysplasia. Out of 182 ulcerative colitis patients low grade dysplasia was present in 17 (9.34%) patients and High Grade dysplasia was present in 4 (2.19%) patients. Dysplasia was higher in patients with extensive colitis and long disease duration.

This Hospital based study thus proves that IBD patients are at the risk of developing dysplasia which may progress to the development of colorectal carcinoma if ignored.

Thus IBD patients should be educated and encouraged to attend the hospital out-patient department regularly and periodic endoscopic surveillance biopsies should be taken to rule out dysplasia, so that proper intervention at the right time can prevent development of colorectal carcinoma and mortality associated with it in these patients.

(Graph 1)

Distribution of cases according to Dysplasia (Table 1)

Age group involved in dysplasia (Table 2)

Microphotographs:

Microphotograph of a case of ulcerative colitis showing crypt abscess and

Low grade dysplasia. H&E stain (10X).

Microphotograph of a case of ulcerative colitis showing crypt abscesses and High grade dysplasia. H&E stain (10X).

DISCUSSION:

This study included total of 210 confirmed IBD case. Males were 127/210 (60.5%) cases of Inflammatory bowel disease and females were 83/210 cases (39.5%). Male: Female ratio was 1.53:1. This pattern is similar to most studies from Asian countries^23,24,25,26 but is unlike western experience^11,27,28. This difference may relate to the custom that males are likely to seek medical advice more commonly than females in relation to colorectal disease.

In this study age ranged from 1 to 80 years. The youngest patient was less than one year old and eldest patient was 80 years old. Mean age is 39.75   years and Standard deviation of 16.04. Maximum number of cases 49 (23.33%)  were seen  in the age group 20-30 years, followed by 43 (20.47%) cases in 40-50 years age group  years, 42 (20%) cases were in  the age group of 30-40 years, 30 (14.28%) cases were in 50-60 age group, 23cases (10.95%) cases were in 10-20 years age group  19 (9.04%) cases were in 60-70 years age group, 2 (0.95%) cases were in 70-80 years age group and 2 (0.95%) cases were belonged to less than 10 years age group. This is almost similar to studies by Das et al.³⁹,Ghoshal et al.³⁰and Pai et al.³¹

Mean duration of disease was 2.43 years. Duration was less than 1 year in 78.57% patients, 1 to 10 years in 14.76% patients, greater than 10 years in 5.71% patients.  In Ulcerative colitis duration of disease varied from less than one year to twenty years while in Crohn’s disease duration of disease varied from less than one year to three years. In this study mean duration was shorter than studies from west b M Leidenius et al¹⁸, this is because of shorter period of follow up in our study.

Ulcerative colitis was present in 182 patients (86.6%), Crohn’s disease in 26 (12.3%) patients and indeterminate colitis in 2 (0.95%). Results were similar to study by from middle east by Mohammad Al Fadda et al³² and   Mohammad B. Satti et al¹⁴ but different from study by Sawczenko A et al³³   from UK and studies from America.^11,27,28,34

Number of biopsy bits received varied from one to Twenty nine. In 61 (29%) cases number of bits were four and in 48 (22.9%) case number of bits were three. The number of bits was much lower to rule out dysplasia with 90% confidence as reported by Rubin et al²¹.

Out of total 210 IBD patients 189, IBD patients (90%) were negative for dysplasia, 21 (10%) IBD patients developed dysplasia. All Crohn’s disease and indeterminate colitis patients were negative for dysplasia.

Out of 182 Ulcerative colitis patients, dysplasia was present in 21 (11.53%) patients, of which Low grade dysplasia was present in 17 (9.34%) patients and High Grade dysplasia was present in 4 (2.19%) patients, 161 (88.46%) ulcerative colitis patients were negative for dysplasia. Results are almost similar to studies by Leidenis et al¹⁸, but less than studies by Friedman et al³⁵.

Dysplasia was present in those patients who had either longer duration of disease, higher age group or extesive colitis. High grade dysplasia was present in four patients, in all four patients age was above fifty years, one patient was in the age group of 50-60 years, two patients were in the age group of 60-70 years, one patient was in age group of 70-80 years, similar to studies by Gyde and Colleagues ¹⁷  , Leidenis et al ¹⁸ Ekbom A et al. from Sweden ¹⁹, Taylor BA et al ²⁰  Friedman et al ³⁵ , Connell et al ³⁶ . All the four patients of ulcerative colitis with high grade dysplasia colectomy was done, none of them had developed adenocarcinoma. Patients with low grade dysplasia were kept on close follow up.

Declaration:

Conflicts of interests: The authors declare no conflicts of interest.

Author contribution: All authors have contributed in the manuscript.

Author funding: Nill

CONCLUSION

This study confirms the development of dysplasia in IBD patients. This study only gives the insight into the development of dysplasia in IBD patients in this geographical area.  Shorter duration of study and Hospital based nature  emphasises the need for much bigger population based studies with long term follow up.

Thus IBD patients should be educated and encouraged to attend the hospital out-patient department regularly and periodic endoscopic surveillance biopsies should be taken to rule out dysplasia, so that proper intervention at the right time can prevent development of colorectal carcinoma in these patients. Endoscopists should take multiple four quadrant biopsies to increase the yield of diagnosis in terms of dysplasia. Newer techniques like chromoendoscopy, magnification endoscopy, narrow band imaging and confocal laser endomicroscopy should be used to diagnose dysplastic lesions at the earliest and prevent development of carcinoma in these patients.

REFERENCES

1. Friedman S, Blumberg RS, Fauci AS, et al. Inflammatory bowel disease. Harrison’s Principles of Internal Medicine. 15thed. New York, NY: McGraw-Hill.
2. Andres PG, Friedman LS. Epidemiology and the natural course of inflammatory bowel disease. Gastroenterol Clin North Am. 1999; 28: 255–281.
3. Crohn’s & Colitis Foundation of America. Living with Crohn’s Disease [educational brochure]. Available at: http: //www. ccfa. org.
4. Loftus EV Jr, Sandborn WJ. Epidemiology of inflammatory bowel disease. Gastroenterol Clin North Am. 2003; 31: 1–20.
5. Salem SN. Non-specific ulcerative colitis in Bedouin Arabs. Lancet 1967; 1: 473-5.
6. Gilat T, Lilos P, Zemishlany Z, Ribak J, Benaroya Y. Ulcerative colitis in the Jewish population of Tel-Aviv Yafo III: clinical course. Gastroenterology 1976; 70: 14-9.
7. Kusakcioglu O, Kusakcioglu A, Oz F. Idiopathic ulcerative colitis in Istanbul. review of 204 cases. Dis Col Rect 1979; 22: 350-5.
8. Mir-Madjlessi SH, Forouzandeh B, Ghadimi R. Ulcerative colitis in Iran: a review of 112 cases. Am J Gastroenterology 1985; 11: 862-6.
9. Hossain J, Al-Faleh FZ, Al-Mofleh I, Al-Aska A, Laajam MA, Al-Rashed R. Does ulcerative colitis exist in Saudi Arabia. Analysis ofthirty-seven cases. Saudi Med J 1989; 10: 360-2.
10. Al-Nakib B, Radhakrishnan S, Jacob GS, Al-Liddawi H, Al-Ruwaih A. Inflammatory bowel disease in Kuwait. Am J Gastroenterology1984; 79: 191-94.
11. Garland CF, Lilienfeld AM., Mendeloff AI et. al. Incidence rates of Ulcerative colitis.The American journal of Gastroenterology 20817 P: 301-263-9000 F: 301-263-9025.
12. Shapiro BD, Lashner BA. Cancer biology in ulcerative colitis and potential use 0f endoscopic surveillance. Gastrointest Endosc Clin N Am. 1997; 7(3): 453-468.
13. Feagins, L. A., R. F. Souza, and S. J. Spechler, Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer. Nat Rev Gastroenterol Hepatol, 2009. 6(5): p. 297-305.
14. Mohammed B. Satti, FRCPath, Abdulaziz Al-Quorain, MD; Yousuf Al-Gindan, MD; Abdulrahman Al-Hamdan, MD Annals of Saudi Medicine, Vol 16, No 6, 1996.
15. Lennard-Jones JE. Cancer risk in ulcerative colitis: surveillance or surgery. Br J Surg 1985; 72(Suppl.): S84–6.
16. Harpaz et al. Colorectal Dysplasia in IBD. Arch Pathol Lab Med 2010 July; Vol. 134.
17. Gyde SN, Prior P, Macartney JC, Thompson H, WaterhouseJA, Allan RN. Malignancy in Crohn’s disease. Gut 1980; 21: 1024-1029
18. M Leidenius, I Kellokumpu, A Husa, M Riihela, P Sipponen. Dysplasia and carcinoma in longstanding ulcerativecolitis: an endoscopic and histological surveillance programme. Gut, 1991, 32, 1521-1525.
19. Ekbom A, Helmick C, Zack M, Adami HO. Ulcerative colitis and colorectal cancer: a population-based study. N Engl J Med. 1990; 323(18): 1228–1233.
20. Taylor BA, Pemberton JH, Carpenter HA, Levin KE, Schroeder KW, Welling DR, et al. Dysplasia in chroniccolitis: implications for colonoscopic surveillance. Dis Colon Rectum 1992; 35: 950-6.
21. Rubin CE, Haggitt RC, Burmer GC, et al. DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. Gastroenterology 1992; 103: 1611–20.
22. Bernstein CN, Shanahan F, Weinstein WM. Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis. Lancet. 1994; 343: 71–74
23. Hossain J, Al-Faleh FZ, Al-Mofleh I, Al-Aska A, Laajam MA, Al-Rashed R. Does ulcerative colitis exist in Saudi Arabia. Analysis ofthirty-seven cases. Saudi Med J 1989; 10: 360-2.
24. Al-Nakib B, Radhakrishnan S, Jacob GS, Al-Liddawi H, Al-Ruwaih A. Inflammatory bowel disease in Kuwait. Am J Gastroenterology1984; 79: 191-94.
25. Mohammed B. Satti, FRCPath, Abdulaziz Al-Quorain, MD; Yousuf Al-Gindan, MD; Abdulrahman Al-Hamdan, MD Annals of Saudi Medicine, Vol 16, No 6, 1996.  
26. Kourosh Masnadi Shirazi, Mohammad Hossein Somi, Yoosef Bafandeh, Firooz Saremi, Nooshin Mylanchy, Parisa Rezaeifar, Nasim Abedi Manesh, Seyed kazem Mirinezhad. Epidemiological and Clinical Characteristics of Inflammatory Bowel Disease in Patients from Northwestern Iran. Middle East Journal of Digestive Diseases/ Vol. 5/ No. 2/ April 2013; 1-7.
27. Ransohoff DF, Riddell RH, Levin B. Ulcerative colitis and colonic cancer: problems in assessing the diagnostic usefulness of mucosal dysplasia. Dis. Colon Rectum 1985; 28: -8.
28. Russel MG, Engels LG, Muris JW, Limonard CB, Volovics A, Brummer RJ, Stockbrugger RW. “Modern life” in the epidemiology of inflammatory bowel disease: a case-control study with special emphasis on nutritional factors. Eur J Gastroenterol Hepatol 1998; 10: 243–249.
29. Das K, et al. Crohn’s disease in India: a multicenter study from a country where tuberculosis is endemic. Dig. Dis. Sci. 2009; 54: 1099-107. 
30. Ghoshal UC et al, Anti-Saccharomyces cerevisiae antibody is not useful to differentiate between Crohn’s disease and intestinal tuberculosis in India. JPostgradMed. 2007; 53: 166-70.
31. Pai CG, et-al. Is Crohn’s disease rare in India. Indian. J. Gastroen-terol. 2000; 19: 17–20.
32. Mohammed Al Fadda Musthafa Chalikandy Peedikayil, Ingvar Kagevi,Inflammatory bowel disease in saudi arabia. Ann.  of Saudi Med 2012; 32(3): 276-28.
33. Sawczenko A, Sandhu B. Presenting features of inflammatory bowel disease in Great Britain and Ireland. Arch Dis Child 2003; 88: 995-1000.
34. Sandborn WJ, Loftus EV Jr, Epidemiology of inflammatory bowel disease. Gastroenterol Clin North Am. 2003; 31: 1–20.
35. Friedman S, Blumberg RS, Fauci AS, et al. Inflammatory bowel disease. Harrison’s Principles of Internal Medicine. 15thed. New York, NY: McGraw-Hill.
36. Connell WR, Talbot IC, Harpaz N, et al. Clinicopathological characteristics of colorectal carcinoma complicating ulcerative colitis. Gut. 1994; 35: 1419 –1423.