Frequency and Pattern of Premalignant and Malignant Lesions among Fecal Immunochemical Test Positive Patients

Introduction

olorectal carcinoma is a large global health problem with a better prognosis if discovered at an early stage. It is a leading cause of illness and mortality all across the world. It is the third most common cancer worldwide and the second most common cause of cancer-related deaths¹. It affects men and women almost equally. Colorectal cancer is mostly a disease in Western-cultured wealthy countries. Australia, New Zealand, Europe, and North America have the highest colorectal carcinoma incidence, while Africa and Asia have the lowest incidence. Developing countries are witnessing an increasing incidence of colorectal carcinoma that is probably related to the adoption of high-risk western behavior with increased smoking, high alcohol, constipation, physical inactivity and unhealthy diets². Colorectal carcinoma can be prevented by the detection and removal of adenomatous polyps and survival is better when the CRC is diagnosed earlier at a localized state. Five-year survival is 90.0% if the disease is diagnosed while still localized (confined to the wall of the bowel).

1. *Dr Chowdhury Sazzad Hyder, Assistant Professor, Department of Surgery, Shaheed Suhrawardy Medical College, Sher-e-Bangla Nagar, Dhaka, Bangladesh; E-mail: [email protected]

2. Dr Mohammad Azim Uddin, Junior Consultant (Surgery), Mymensingh Medical College Hospital, Mymensingh, Bangladesh

3. Dr Mohammad Tanvir Jalal, Associate Professor of Colorectal Surgery, BSMMU, Dhaka, Bangladesh

4. Dr Saiyeda Sinthia Karim, Associate Professor of Pathology, National Institute of Laboratory Medicine and Referral Center, Dhaka, Bangladesh

5. Professor Dr Md Abu Taher, Professor of Colorectal Surgery, BSMMU, Dhaka, Bangladesh

6. Professor Dr Kamrun Nahar, Professor of Colorectal Surgery, BSMMU, Dhaka, Bangladesh

7. Professor Dr Md Shahadat Hossain, Professor of Colorectal Surgery, BSMMU, Dhaka, Bangladesh

8. Professor Dr Md Shahadot Hossain Sheikh, Professor & Chairman, Department of Colorectal Surgery, BSMMU, Dhaka, Bangladesh

9. Dr Md Shahidul Islam, Assistant Professor of Colorectal Surgery, BSMMU, Dhaka, Bangladesh

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*for correspondence

But this percentage falls to 68.0% for regional disease with lymph node involvement and 10.0% if distant metastasis is present. Screening can affect the early detection and prevention through polypectomy and improved treatment. Greater incidence and mortality reduction could be achieved if a greater proportion of adults received regular screening³. Most colorectal cancers are initially related to benign colonic adenomas. Removal of tubular, tubulovillous, villous and serrated adenoma (precursor lesions) can reduce colorectal carcinoma incidence. Screening for CRC has shown beneficial for reducing mortality. For over three decades, colonoscopy has been the gold standard for detecting adenomas and adenocarcinoma. However, this procedure can have serious complications, and be uncomfortable and anxiety-inducing⁴. Other limitations are that it is costly and less available in many developing and underdeveloped countries. One of the alternative cheaper but reliable methods to limit colonoscopy is a stool-based test, Fecal Immunochemical Test (FIT). Prior to a colonoscopy, stool testing can predict advanced neoplasms. The fecal immunochemical test (FIT) has been shown to have both high sensitivity and specificity in identifying colorectal carcinoma and advanced polyps throughout the colon in a population with an average risk for colon cancer. A meta-analysis of nineteen such studies showed that the sensitivity and specificity of a single Fecal Immunochemical test result were similar to those of multiple samples⁵. Organized colorectal carcinoma screening programs with Fecal Immunochemical tests have been implemented in Europe and Australia. The Fecal Immunochemical test is more accurate than guaiac-based FOBT for advanced neoplasia⁶. It is an outdoor surveillance method, cost-effective, easy to do, less time-consuming and has patient convenience. FIT can be used even in remote areas. There is no need for preparation, no medication or food restrictions as like in FOBT and patients prefer the Fecal Immunochemistry test to guaiac tests⁷. It has been clinically proved that the performance of a single sample Fecal Immunochemistry Test is better than traditional three sample gFOBT⁸. The accuracy of FIT is dependent on adenoma characteristics such as size, location, shape, histology, gender and even age⁹. By making use of the Fecal Immunochemical Test, the treatment strategy for ulcerative colitis could be determined in many situations without performing a colonoscopy¹⁰. Much colonic pathology has a bleeding tendency. Most of them show occult bleeding, especially benign and adenomatous polyps, premalignant lesions, ulcers, and malignant lesions. But they may not have obvious clinical features to be detected earlier. Most of these patients present with advanced disease. If we detect the lesions earlier by any easy, available and simple method, many malignancies can be prevented and can save many lives. Fecal Immunochemical Test is a less expensive technique for the early detection of colonic pathology and it will be well accepted for our socioeconomic status. Despite colonoscopy being highly accurate and therapeutic, it is not easily available in remote areas. The current study is aimed to assess the usefulness of the Fecal Immunochemical Test in the detection of any colonic pathology, especially the premalignant and malignant lesions, and also to evaluate the feasibility of FIT as a screening tool for CRC in our socioeconomic settings.

Objective of the study was To observe the frequency and pattern of premalignant and malignant lesions among Fecal Immunochemical Tests (FIT) positive patients.

Methods

This observational cross-sectional study was conducted at the Department of Colorectal Surgery, Bangabandhu Sheikh Mujib Medical University, Bangladesh. The study duration was 1 year, from July 2019 to August 2020. At the initial stage, a total of 510 participants were selected among the patients attending the outdoor department of BSMMU colorectal surgery having constipation, changes in bowel habits, lack of appetite, per rectal mucous discharge, abdominal pain, etc., through a purposive sampling method. After following the inclusion and exclusion criteria and informing the participants of the study regarding study purpose, a total of 105 patients were selected as the final sample size who had given written consent to participate in the study. Ethical clearance for the study was taken from the Institutional Review Board (IRB) of BSMMU (Memo no.: BSMMU/2019/8223 dated: 30-07-2019) prior to the commencement of this study. Data was collected by a predesigned proforma involving questionnaire, clinical findings, preoperative investigations, stool test for Fecal Immunochemical Test, and colonoscopy. Computer-based statistical analysis was carried out with appropriate techniques and systems for data analysis.

Inclusion criteria: i) Patients Aged between 40-70 years, ii) Patients who had changes in bowel habit, lack of appetite, per rectal mucous discharge, abdominal pain, iii) FIT (Fecal Immunochemical Test) positive participants and iv) Patients who had given consent to participate in the study.

Exclusion criteria: i) FIT negative participants, ii) Patients presented with visible per rectal bleeding, iii) Patients with known cases of FAP, Ulcerative colitis, Crohn’s disease, or familial colorectal cancer, iv) Patients with a personal history of known colorectal carcinoma, and adenoma, v) Unable to answer the criteria question and vi) Exclude those affected with other chronic diseases etc.

Results

It was observed that one-fourth (26.7%) of the patients belonged to the age group of 50-59 years among the male population and 23(21.9%) the in female population. The mean age was 51.73±7.97 years with an age range of the participants from 40 to 70 years were shown in Table I.

Table I: Age and gender distribution of the participants (n=105)

Age (in years)	Male		Female		Total
Age (in years)	Number of patients (n)	Percentage (%)	Number of patients (n)	Percentage (%)	Total
40-49	24	22.9	11	10.5	35
50-59	28	26.7	23	21.9	51
60-69	12	11.4	05	04.8	17
≥70	02	01.9	00	00.0	02
Mean±SD	51.73±7.97
Range	40-70

It was observed (Table II) that the majority (80.95%) of the patients had constipation, followed by 40.0% who had abdominal pain, 33.33% who had P/R mucous discharge and 12.38% had changes in their bohabitsabit and 6.67% had a lack of appetite. Multiple complications were present among participants.

Table II: Distribution of the study patients by clinical symptoms (n=105)

Clinical symptoms	Number of patients (n)	Percentage (%)
Changes in bowel habit	13	12.38
P/R Mucous discharge	35	33.33
Abdominal Pain	42	40.00
Lack of appetite	07	6.67
Constipation	85	80.95

It was observed (Table III) that 14.3% of patients showed normal findings. More than one-third (40.0%) of patients had pedunculated polyps. Eleven (10.5%) patients had nonspecific ulcers; three (2.9%) patients had growth and 13(12.4%) hemorrhoidshoid.

Table III: Distribution of the study patients by colonoscopic findings (n=105)

Colonoscopic findings	Number of patients (n)	Percentage (%)
Normal	15	14.29
Polyps
Pedunculated	42	40.00
Sessile/broad-based	16	15.24
Ulcers
Nonspecific	11	10.48
Ulcerative colitis	01	00.95
Crohn’s	02	01.90
Growth	03	02.86
Hemorrhoid	13	12.38
Diverticulosis	02	01.90

Table IV shows the distribution of the study patients by colonoscopic and histopathological findings. It was observed that polyps had the highest prevalence at 58(55.2%), among which 42 had pedunculated polyps and 16 had sessile or flat polyps. Histopathological findings showed that almost half (44.8%) of patients had tubular adenoma with low-grade dysplasia in pedunculated polyps and 10(17.2%) in Sessile/ Flat polyps. Other than polypoidal lesions, there weres ulcers present in 14(13.3%) patients. Among ulcer cases, almost two-thirds (64.3%) of patients had nonspecific colitis in Ulcer. In cases of normal findings, hemorrhoid and diverticulosis biopsies were not done.

Table IV: Distribution of study patients by colonoscopic and histopathological findings (n=105)

Sample		Histopathological findings	Number (n)	Percentage (%)
Polyp (n=58)	Pedunculated (n=42)	Tubular adenoma with LGD	26	44.8
		SSA/HP no dysplasia	06	10.3
		Villous adenoma dysplasia	03	05.2
		Tubulovillous with dysplasia	02	03.5
		SSA/HP with dysplasia	00	00.0
		Tubular adenoma with HGD	04	06.9
		Malignancy	01	01.7
	Sessile/ Flat (n=16)	Tubular adenoma with LGD	10	17.2
		SSA/HP no dysplasia	03	05.2
		Villous adenoma dysplasia	00	00.0
		Tubulovillous with dysplasia	00	00.0
		SSA/HP with dysplasia	00	00.0
		Tubular adenoma with HGD	02	03.5
		Malignancy	01	01.7
Ulcer (n=14)		Non specific colitis	09	64.3
		Ulcerative colitis	01	07.1
		Crohn’s	02	14.3
		TB	02	14.3
		Malignant	00	00.0
Growth (n=3)	Adeno Carcinoma		03	100.0
Normal (n=15)			15	100.0
Hemorrhoid	Biopsy not done		13	86.67
Diverticulosis	Biopsy not done		02	13.33

It was observed (Table V) that more than half (52.0%) of the patients had precursor lesions among which the highest number was observed in polyp with low-grade dysplasia 36(34.3%). Polyps with high-grade dysplasia were present in 11(10.4%). 4.8% had malignancy. Fifty (50) patients had benign findings. In total, 14.3% had normal findings, 10.4% had nonspecific ulcers, 12.4% had hemorrhoids, 8.6% had polyps without any dysplasia and 1.9% had diverticulosis.

Table V: Distribution of the study patients by precursor lesions and benign findings (n=105)

	Number (n)	Percentage (%)
Precursor Lesions (n=55)
Polyp with Low-Grade dysplasia	36	34.3
Polyp with High-Grade dysplasia	11	10.4
Malignancy	05	04.8
UC	01	01.0
Crohn’s	02	01.9
Benign findings (n=50)
Normal	15	14.3
Polyps without dysplasia	09	08.6
Nonspecific ulcers	11	10.4
Haemorrhoid	13	12.4
Diverticulosis	02	01.9

Discussion

Colorectal cancer (CRC) is the third most common cancer in the Western world and is the second most deadly cancer⁵. However, early detection of cancer has now been shown to reduce mortality. In addition, because most CRCs are initially related to benign colonic adenomas, removal of tubular adenoma (TA), tubulovillous adenoma (TVA) and serrated adenomas could reduce CRC incidence. As a result, most Western nations have undertaken population screening programs. There are different programs used to perform colonoscopy screening¹¹. Among these various techniques, the fecal immunochemistry test (FIT) has been shown to have both high sensitivity and specificity in identifying CRC and advanced polyps throughout the colon¹². Many patients with colon cancer do not present with symptoms until it is advanced and detection in the early stage can only be achieved by screening of asymptomatic person. Nevertheless, maximum patients present lately with distance metastases when there is nothing to treat except palliative therapy. Considering the facts and figures, the present observational study was conducted in the Department of Colorectal Surgery, Bangabandhu Sheikh Mujib Medical University (BSSMU) and some private hospitals from July 2019 to June 2020 among 105 Fecal Immunochemical Test (FIT) positive patients. In this study, regarding the distribution of the study patients by age and sex, it was observed that the highest number of patients (48.6%) belong to the sixth decade of life, followed by 35(33.3%) in their fifth decade. The male: Female ratio was 1.7:1 and the overall mean age was 51.73±7.97 years. There was another study with participants from a similar age range of 40-70 years, where the mean age was 57 years, which was not that different from our findings⁷.^[7] There was no significant age difference between the male and female participants of our study, which was similar to the findings of another study⁵. Some other studies with younger study participants reported that the incidence rate among adults younger than age 50 years is increasing due to an increase in left-sided tumors^13,14. Male prevalence was higher in this study, which was supported by the findings of another 2017 study⁵. The main complaints of the study patient were constipation, followed by abdominal pain, P/R mucous discharge, changes in bowel habits and lack of appetite. Constipation had the highest incidence rate among the participants, observed in 80.95% of the participants. These findings were similar to the findings of a study conducted by Fong et al.¹⁵. In a colonoscopy, the commonest diagnosed cases were polyps of various types, observed in 58 cases. Colonoscopy also revealed normal findings in 14.3% of cases and ulcers in 13.3% of cases. 12.38% had hemorrhoids, and 2.86% had abnormal growth found in colonoscopy. The normal findings and hemorrhoid cases were not undertaken for biopsies. FIT positive findings with normal findings in colonoscopy may be due to amoebiasis or shigellosis. Among the remaining patients, histopathological diagnosis revealed that the commonest diagnosis was tubular adenoma with low-grade dysplasia, present in 44.8%. Others were sessile serrated adenoma/hyperplastic polyp (SSA/HP) with no dysplasia in 10.3%, villous adenoma with dysplasia in 5.2%, Tubulovillous adenoma with dysplasia in 3.5%, Tubular adenoma with high-grade dysplasia in 6.9% and malignancy in 1.7%. In sessile polyps cases, histopathologically 17.2% were TA with low-grade dysplasia, followed by 5.2% in SSA/HP with no dysplasia, 3.5% in TA with high-grade dysplasia, and 1.7% in malignancy. In the present study, the detection rate of advanced polyp was 22.4% and the non-advanced polyp was 77.6%. Another study supported our findings, where despite at least 20 types of pathologies seen on colonoscopy, normal cases constituted the majority (32.7%)¹⁶. FIT before colonoscopy indicates a greater chance of detecting advanced adenoma or invasive adenoma. Regarding the distribution of study patients by precursor lesions and benign findings, it was observed that over half (52%) of the participants had precursor lesions, among which the highest number (34.3%) was observed in a polyp with low-grade dysplasia. Almost similar findings were observed in another study, where almost 82.8% of the lesions were precancerous with tubular type predominance¹⁷.

Limitations of the study

The study was conducted in a single hospital with a small sample size. So, the results may not represent the whole community.

Conclusion

The fecal immunochemical test can predominantly detect adenomas, especially advanced adenoma and precursor lesions. The study finding showed that both non neoplastic, neoplastic polyps and ulcers had occult bleeding. So they became FIT positive. Though colonoscopy is the gold standard in the detection of polyps, ulcers, or malignant lesions, FIT can be a good supportive tool for screening.

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